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Clinical NLP Lab 29

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: OBJECTIVE The purpose of the present study was to evaluate the effects of a school-based , 2-year , multi-component intervention on BMI , eating and physical activity behaviour in Fl and ers , Belgium , targeting children aged 3 - 6 years in communities of high and low socio-economic status ( SES ) . DESIGN Cluster-r and omized controlled trial . SETTING Thirty-one pre- primary and primary schools in three different intervention communities and three paired-matched ( on SES profile ) control communities in Fl and ers , Belgium . SUBJECTS BMI Z-scores at baseline and follow-up were calculated for 1102 children . Question naires with sociodemographic data and FFQ were available from 694 of these 1102 children . RESULTS No significant effects were found on BMI Z-scores for the total sample . However , there was a significant decrease in BMI Z-score of 0·11 in the low-SES intervention community compared with the low-SES control community , where the BMI Z-score increased by 0·04 ( F = 6·26 , P = 0·01 ) . No significant intervention effects could be found for eating behaviour , physical activity or screen-time . There were no significant interaction effects of age and gender of the children on the outcome variables . CONCLUSIONS Although no significant effects were found for BMI Z-scores in the total sample , this intervention had a promising effect in the low-SES community of reducing excess weight gain among young children OBJECTIVE To evaluate the impact of nutrition education in kindergartens and to promote healthy dietary habits in children . DESIGN Prospect i ve cohort study . Four kindergartens with 1252 children were r and omized to the intervention group and three with 850 children to the control group . The personal nutritional knowledge , attitudes and dietary behaviours of the parents were also investigated . Each month , children and parents in the intervention group participated in nutrition education activities . The main outcome measures were anthropometrics and diet-related behaviours of the children and the nutritional knowledge and attitudes of the parents at baseline , 6 months ( mid-term ) and 1 year ( post-test ) . Baseline demographic and socio-economic characteristics were also collected . SETTING Seven kindergartens from Hefei , the capital city of Anhui Province , eastern China . SUBJECTS Two thous and one hundred and two 4- to 6-year-old pre-schoolers from seven kindergartens participated . RESULTS The prevalence of children 's unhealthy diet-related behaviours decreased significantly and good lifestyle behaviours increased in the group receiving nutrition education compared with controls . Parental eating habits and attitudes to planning their children 's diets also changed appreciably in the intervention group compared with the control group ( P < 0.05 ) . However , there were no statistically significant differences in children 's height , weight , height-for-age Z-score or weight-for-age Z-score between the two groups . CONCLUSIONS Kindergarten-based nutrition education improves pre-schoolers ' lifestyle behaviours and brings about beneficial changes in parents ' attitudes to planning their children 's diets and their own personal eating habits BACKGROUND School programs can be effective in modifying knowledge , attitudes , and habits relevant to long-term risk of chronic diseases associated with sedentary lifestyles . As part of a long-term research strategy , we conducted an educational intervention in preschool facilities to assess changes in preschoolers ' knowledge , attitudes , and habits toward healthy eating and living an active lifestyle . METHODS Using a cluster design , we r and omly assigned 14 preschool facilities in Bogotá , Colombia to a 5-month educational and playful intervention ( 7 preschool facilities ) or to usual curriculum ( 7 preschool facilities ) . A total of 1216 children aged 3 - 5 years , 928 parents , and 120 teachers participated . A structured survey was used at baseline , at the end of the study , and 12 months later to evaluate changes in knowledge , attitudes , and habits . RESULTS Children in the intervention group showed a 10.9 % increase in weighted score , compared with 5.3 % in controls . The absolute adjusted difference was 3.90 units ( 95 % confidence interval [ CI ] , 1.64 - 6.16 ; P < .001 ) . Among parents , the equivalent statistics were 8.9 % and 3.1 % , respectively ( absolute difference 4.08 units ; 95 % CI , 2.03 to 6.12 ; P < .001 ) , and among teachers , 9.4 % and 2.5 % , respectively ( absolute difference 5.36 units ; 95 % CI , -0.29 - 11.01 ; P = .06 ) . In the intervened cohort 1 year after the intervention , children still showed a significant increase in weighted score ( absolute difference of 6.38 units ; P < .001 ) . CONCLUSIONS A preschool-based intervention aim ed at improving knowledge , attitudes , and habits related to healthy diet and active lifestyle is feasible , efficacious , and sustainable in very young children Background The onset of inadequate behaviors leading to the development of risk factors for chronic diseases is known to occur early in life . An effective program for health promotion should therefore focus on children and their environment , as the starting point for behavior development . The overarching objective of the Program SI ! ( Salud Integral - Comprehensive Health ) is to intervene at the school level , to establish and develop life-lasting habits that will help preserving health during adulthood . The Program SI ! comprises five consecutive subprograms according to the five stages of education in Spain , the first being in preschoolers . This study aims to evaluate the efficacy of Program SI ! to establish and improve lifestyle behaviors in children ( preschoolers aged 3–5 years ) , their parents , and teachers , and also improving the school environment . A secondary objective is to evaluate improvements in cardiovascular health-related markers ( anthropometric parameters , blood pressure , and dietary and physical activity patterns ) in these same children . Methods / design 24 public schools from the city of Madrid ( Spain ) were allocated through stratified r and omization to intervention or control . The intervention schools follow the Program SI ! , which provides didactic units , emotions cards , healthy tips , and online re sources . The intervention schools integrate the Program SI ! into their scholar curriculum organized in four complete weeks during each academic year during the 3 years of preschool education . Control schools follow their normal curriculum . Primary outcomes are 1-year , and 3-year changes from baseline of scores for knowledge , attitudes , and habits ( KAH ) of children , their parents and teachers in regards to a healthy lifestyle . Secondary outcomes are 1-year , and 3-year changes from baseline in clinical and anthropometric parameters of children . Discussion The Program SI ! is a long-term health promotion program starting in 3 years old . It incorporates the traditional areas of intervention ( diet and physical activity ) , introducing additional components such as knowledge of the human body and management of emotions to achieve a comprehensive intervention . The Program SI ! is design ed to be an effective , sustainable health promotion program for the adoption of healthy behaviors from early in life . Trial registration Trial registration number : OBJECTIVE To determine the impact of an implementation intervention design ed to introduce policies and practice s supportive of healthy eating in centre-based child-care services . Intervention strategies included staff training , re sources , incentives , follow-up support , and performance monitoring and feedback . DESIGN A quasi-experimental design was used to assess change over 20 months in healthy eating policy and practice in intervention and comparison child-care services . SETTING The Hunter New Engl and ( HNE ) region of New South Wales ( NSW ) , Australia . SUBJECTS All centre-based child-care services ( n 287 ) in the intervention region ( HNE ) were invited and 240 ( 91 % response rate ) participated . Two hundred and ninety-six services in the rest of NSW were r and omly selected as a comparison region and 191 participated ( 76 % response rate ) . A sub- analysis was conducted on those services that provided children food ( n 196 at baseline and n 190 at follow-up ) . Ninety-six provided menus for analysis at baseline ( HNE , n 36 ; NSW , n 50 ) and 102 provided menus at follow-up ( HNE , n 50 ; NSW , n 52 ) . RESULTS Services in the intervention region were significantly more likely to provide only plain milk and water for children ( P = 0.018 ) and to engage parents in nutrition policy or programmes ( P = 0.002 ) . They were also more likely ( P = 0.056 ) to have nutrition policy on home packed food . In addition , menus of services that provided lunch were significantly more likely to comply with healthy eating guidelines for sweetened drinks ( P < 0.001 ) , fruit ( P < 0.001 ) and vegetables ( P = 0.01 ) . CONCLUSIONS An implementation intervention was able to modify policy and practice in a large number of child-care services so that they were more supportive of healthy eating Objective To test the effect of a multidimensional lifestyle intervention on aerobic fitness and adiposity in predominantly migrant preschool children . Design Cluster r and omised controlled single blinded trial ( Ballabeina study ) over one school year ; r and omisation was performed after stratification for linguistic region . Setting 40 preschool classes in areas with a high migrant population in the German and French speaking regions of Switzerl and . Participants 652 of the 727 preschool children had informed consent and were present for baseline measures ( mean age 5.1 years ( SD 0.7 ) , 72 % migrants of multicultural origins ) . No children withdrew , but 26 moved away . Intervention The multidimensional culturally tailored lifestyle intervention included a physical activity programme , lessons on nutrition , media use ( use of television and computers ) , and sleep and adaptation of the built environment of the preschool class . It lasted from August 2008 to June 2009 . Main outcome measures Primary outcomes were aerobic fitness ( 20 m shuttle run test ) and body mass index ( BMI ) . Secondary outcomes included motor agility , balance , percentage body fat , waist circumference , physical activity , eating habits , media use , sleep , psychological health , and cognitive abilities . Results Compared with controls , children in the intervention group had an increase in aerobic fitness at the end of the intervention ( adjusted mean difference : 0.32 stages ( 95 % confidence interval 0.07 to 0.57 ; P=0.01 ) but no difference in BMI ( −0.07 kg/m2 , −0.19 to 0.06 ; P=0.31 ) . Relative to controls , children in the intervention group had beneficial effects in motor agility ( −0.54 s , −0.90 to −0.17 ; P=0.004 ) , percentage body fat ( −1.1 % , −2.0 to −0.2 ; P=0.02 ) , and waist circumference ( −1.0 cm , −1.6 to −0.4 ; P=0.001 ) . There were also significant benefits in the intervention group in reported physical activity , media use , and eating habits , but not in the remaining secondary outcomes . Conclusions A multidimensional intervention increased aerobic fitness and reduced body fat but not BMI in predominantly migrant preschool children . Trial registration Clinical Trials NCT00674544 The preschool years offer an opportunity to interrupt the trajectory toward obesity in black children . The Hip-Hop to Health Jr. Obesity Prevention Effectiveness Trial was a group-r and omized controlled trial assessing the feasibility and effectiveness of a teacher-delivered weight control intervention for black preschool children . The 618 participating children were enrolled in 18 schools administered by the Chicago Public Schools . Children enrolled in the nine schools r and omized to the intervention group received a 14-week weight control intervention delivered by their classroom teachers . Children in the nine control schools received a general health intervention . Height and weight , physical activity , screen time , and diet data were collected at baseline and postintervention . At postintervention , children in the intervention schools engaged in more moderate-to-vigorous physical activity ( MVPA ) than children in the control schools ( difference between adjusted group means = 7.46 min/day , P = 0.02 ) . Also , children in the intervention group had less total screen time ( -27.8 min/day , P = 0.05 ) . There were no significant differences in BMI , BMI Z score , or dietary intake . It is feasible to adapt an obesity prevention program to be taught by classroom teachers . The intervention showed positive influences on physical activity and screen time , but not on diet . Measuring diet and physical activity in preschool children remains a challenge , and interventions delivered by classroom teachers require both intensive initial training and ongoing individualized supervision Dietary patterns are useful in nutritional epidemiology , providing a comprehensive alternative to the traditional approach based on single nutrients . The Cardiovascular Risk in Young Finns Study is a prospect i ve cohort study with a 21-year follow-up . At baseline , detailed quantitative information on subjects ' food consumption was obtained using a 48 h dietary recall method ( n 1768 , aged 3 - 18 years ) . The interviews were repeated after 6 and 21 years ( n 1200 and n 1037 , respectively ) . We conducted a principal component analysis to identify major dietary patterns at each study point . A set of two similar patterns was recognised throughout the study . Pattern 1 was positively correlated with consumption of traditional Finnish foods , such as rye , potatoes , milk , butter , sausages and coffee , and negatively correlated with fruit , berries and dairy products other than \n Output:\n " }, { "from": "agent", "value": "Children 's dietary food intake and food choices were significantly influenced .\nInterventions to prevent obesity did not significantly change children 's anthropometric measures or had mixed results .\nEvidence was more convincing if interventions were multi-component , addressed physical activity and diet , targeted individual-level and environmental-level determinants and engaged parents .\nPositive outcomes were mostly facilitated by research ers/external experts and these results were not replicated when implemented in centres by ECEC providers without this support ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: BACKGROUND Although adverse effects of severe chronic stress on immunocompetence and physical well-being in older adults have been reported , the immune response to less severe life stress among healthy older adults , particularly among women , is not well understood . Interleukin-6 ( IL-6 ) has been considered a good overall indicator of immune functioning in older adults because of its contribution to the pathogenesis of several age-related conditions such as osteoporosis . Regulation of IL-6 is impaired in elderly adults , and levels of IL-6 increase with stress and depression . This research cross-sectionally examined levels of IL-6 in three groups of healthy older women with varying levels of life stress and mood disturbance and a healthy group of young women . METHODS Subjects included 18 caregivers of Alzheimer 's patients , 17 older women assessed one month before relocation of their residence , 15 nonmoving and noncaregiving older women , and 20 younger women . Subjects completed the Profile of Mood States ( POMS ) and had early morning blood draws . RESULTS Alzheimer 's caregivers reported significantly greater distress than women of all other groups . IL-6 levels in caregivers were significantly higher than those of all other women . The older women had significantly higher IL-6 than young controls , but there were no significant differences in IL-6 between movers and older controls . Among all women , greater depression and distress were related to higher levels of IL-6 . CONCLUSIONS These findings suggest that in older women , chronic stressors are associated with significant elevations in IL-6 over and above the elevations associated with normal aging , but that moderate stressors may not be related to appreciable elevations in IL-6 Vascular endothelial growth factor ( VEGF ) has been implicated in neuronal survival , neuroprotection , regeneration , growth , differentiation , and axonal outgrowth , which are known to be involved in the pathophysiology of major depressive disorder ( MDD ) . Recently , the VEGF mRNA expression in the peripheral leukocytes from Alzheimer 's disease or cardiovascular disease was reported to be changed . We hypothesized that the expression of the VEGF mRNA in the peripheral leukocytes may be a good c and i date for the biological marker for MDD . Thirty two patients with MDD and age- and sex-matched control subjects were included in this expression study . The VEGF mRNA levels in the peripheral leukocytes from drug-naive MDD patients were significantly higher than those from the control subjects and the magnitude of the decrease of VEGF mRNA after 8-week treatment significantly correlated with clinical improvement . Then , we genotyped two single nucleotide polymorphic markers of VEGF gene , which were reported to be associated with amyotrophic lateral sclerosis and Alzheimer 's disease , in patients with MDD and control subjects ( n=154 , each ) . We did not find any significant association between these markers and MDD or its clinical subtypes . Our investigation indicates that the higher expression levels of VEGF mRNA in the peripheral leukocytes are associated with the depressive state and their recovery after treatment may be associated with the clinical improvement The association between somatic illness and psychiatric illness is well established in adults but is less clear in childhood and adolescence . A cohort of over 700 r and omly selected children in Upstate New York were studied from ages 1 - 10 years in 1975 to young adulthood in 1992 . Psychiatric and physical health were assessed by means of follow-up youth and parent interviews at 8- , 2 1/2- , and 6-year intervals ( in 1983 , 1985 - 1986 , and 1991 - 1993 ) . Cross-sectional and longitudinal analyses investigated : 1 ) the consistency of the relation between physical illness and mental illness in childhood ; 2 ) the specificity of major depressive disorder ( MDD ) in accounting for the relation ; 3 ) the specificity of immunologically mediated medical disorders in this relation ; and 4 ) whether this relation was attributable to risks associated with low socioeconomic status . Cross-sectionally , ill health was associated with increased risk of psychiatric disorders at all ages , with significant odds ratios ( ORs ) ranging from 1.76 to 3.26 . In prospect i ve analyses , ill health increased the risk of new-onset MDD at all ages ( ORs = 2.05 - 4.48 ) . MDD also predicted subsequent ill health , independent of prior health problems ( ORs = 3.81 and 4.04 ) . Relations were not attributable to familial socioeconomic status . Associations were particularly strong between MDD and medical disorders associated with alterations in immunologic factors ( ORs = 1.83 - 6.41 ) . Theories of common immune-mediated vulnerabilities to medical illness and depression are consistent with these associations Abstract .Acute exacerbations may complicate the course of pregnancy and the postpartum period in patients with relapsing-remitting multiple sclerosis ( RRMS ) . To evaluate relapse rate and the effect of immunomodulatory treatment with intravenous immunoglobulin ( IVIg ) during pregnancy and the postpartum period we retrospectively analysed the data of 108 pregnant RRMS patients . Group I patients were not treated , Group II patients were treated with IVIg 0.4 g/kg body weight/day for 5 consecutive days within the first week after delivery with additional booster doses of 0.4 g/kg body weight/day at 6 and 12 weeks postpartum ( defined as 12 weeks after labor ) , and Group III patients were treated continuously with IVIg during gestation and the postpartum period ( 0.4 g/kg body weight/day for 5 consecutive days within the 6–8 weeks of gestation with additional booster doses of 0.4 g/kg body weight/day once every 6 weeks until 12 weeks postpartum ) . All patients underwent antenatal care and fetal ultrasonographic surveillance examinations . Relapse rate per woman per year during the pregnancy and the postpartum period as well as neonatal outcome data and IVIg related adverse events were analysed . Relapse rate per woman per year for patients treated with IVIg for the whole pregnancy and postpartum period ( Group III , N = 28 ) compared with the untreated Group I patients ( N = 39 ) were as follows : first trimester 0.43 vs. 0.72 , second trimester 0.15 vs. 0.61 , third trimester 0.0 vs. 0.41 , and postpartum period 0.28 vs.1.33 ( p < 0.05 ) . Patients treated with IVIg only during the postpartum period ( Group II , N = 41 ) also showed a decrease in relapse rate compared with untreated Group I patients , 0.58 vs. 1.33 ( p = 0.012 ) . The mean maternal age , disease duration , gestational age at delivery and fetal delivery weight did not significantly differ between the three groups . Mode of delivery , obstetrical complications , the use of epidural analgesia and breast-feeding , did not affect postpartum relapse rate . No severe adverse events were associated with IVIg treatment either during the pregnancy or postpartum period for the patients and newborns . We conclude that in RRMS patients IVIg treatment could be considered as an optional treatment to reduce the incidence of pregnancy and postpartum-related relapses . Further r and omized double-blind studies are needed to confirm our findings Although tumor necrosis factor-alpha ( TNF-α ) has been recognized to be involved in the pathogenesis of major depressive disorder ( MDD ) for a long time , only few studies so far investigated the effects of antidepressant , venlafaxine on TNF-α and the results are inconsistent . Moreover , the association between plasma TNF-α levels and suicide accompanied with MDD is entirely unknown . To eluci date these relationships , in the present study , 64 first-episode drug-naïve MDD patients and 64 matched healthy controls were recruited . Total 61 MDD patients received 8-week venlafaxine treatment and they were divided into responders and non-responders according to the reduction rate of HRSD-17 . Prior to venlafaxine treatment , both responders and non-responders shared a similar plasma TNF-α ( p=0.33 ) , which was significantly decreased following venlafaxine treatment ( p<0.001 , p=0.03 , respectively ) . Compared to non-responders , the responder group had a greater reduction in TNF-α ( p=0.01 ) , which was associated with the greater reduction rate of HRSD-17 ( B=1.02 , p=0.01 ) . In addition , the plasma TNF-α levels were equally higher in both suicidal and non-suicidal MDD patients ( p=0.84 ) compared to the healthy controls on admission ( p=0.001 , p=0.03 , respectively ) . Together , our data suggest that MDD per se rather than suicide is associated with the elevated plasma TNF-α , which can be inhibited with venlfaxine monotherapy . The extent of TNF-α reduction may be associated with the efficiency of venlafaxine It has been postulated that major depression may be accompanied by significant changes in cell-mediated and humoral immunity related to the pathophysiology or pathogenesis of that illness . We explored the role of 2 cytokines , IL-12 and TGF-beta1 , which represent the cytokines of the Th1 and Th3 types , in the pathophysiology of major depressive disorder ( MDD ) . Cytokine levels were measured in 30 major depressed patients at the time of admission and 6 weeks after effective antidepressant treatment ; levels were measured once in 30 normal controls . At the time of admission , TGF-beta1 levels of MDD patients showed no differences from normal controls , but IL-12 was significantly higher than in normal controls . However , the IL-12/TGF-beta1 ( Th1/Th3 ) ratios of depressed patients were not different from those of controls . In MDD patients , IL-12 values were significantly decreased after treatment , while TGF-beta1 levels were significantly increased . IL-12/TGF-beta1 ratios of patients were significantly decreased after treatment compared with before treatment . There were no significant correlations between changes in the cytokine levels and changes in scores representing the severity of depression . These findings suggest that major depression is accompanied by immune activation during the acute depressed state , and antidepressant treatments have anti-inflammatory effects BACKGROUND Psychiatric side effects of interferon alfa are frequently observed in the therapy of patients with chronic hepatitis C infection . The goal of the present study was to assess prospect ively the incidence , spectrum , and extent of psychiatric symptoms of patients receiving interferon alfa therapy as compared with an untreated reference group . METHOD 104 patients with chronic hepatitis C were consecutively enrolled in a prospect i ve longitudinal study . The treatment group ( N = 84 ) received interferon alfa-2b for up to 12 months , and the reference group ( N = 20 ) received no treatment . Patients who began treatment between November 1996 and August 1998 ( N = 44 ) received interferon alfa-2b , 5 million units 3 times per week . Patients who began treatment in September 1998 or later ( N = 40 ) received a combination of interferon alfa-2b , 3 to 5 million units 3 times per week , and ribavirin , 1000 - 1200 mg/day . Diagnostic scores for depression and anxiety were obtained by means of the psychometric instrument Hospital Anxiety and Depression Scale , and scores for anger/hostility were obtained with the Symptom Checklist-90 Revised . RESULTS In contrast to the untreated reference group , we found significantly increased scores for depression ( p < .001 ) and anger/hostility ( p < .001 ) during interferon alfa therapy in the treatment group . Even before therapy , scores of those in the treatment group were above the respective cutoff values for clinical ly relevant symptoms of depression in 15.5 % of the patients , anxiety in 13.1 % of the patients , and anger/hostility in 11.3 % of the patients . These proportions rose to 35.0 % ( depression ) , 25.6 % ( anxiety ) , and 24.5 % ( anger/hostility ) . The cumulative frequency of clinical ly relevant emotional distress ( depression , anxiety , or anger/hostility ) during interferon alfa therapy was 57.7 % , as compared with 22.5 % before therapy . However , interferon alfa therapy had to be stopped prematurely because of untreatable psychiatric symptoms in only 8.3 % of patients . CONCLUSION In view of the high frequency and extent of psychiatric symptoms with interferon alfa therapy , we recommend a close follow-up of patients receiving this therapy with respect to potential limiting mood changes \n Output:\n " }, { "from": "agent", "value": "The presence of major depressive disorder ( MDD ) with suicidal ideation/attempts was associated with differences in inflammatory cytokine profile when compared to that without suicidal ideation/attempts .\nMost suicide attempters or subjects with suicidal ideation showed an imbalance of the immune system but this does not imply the existence of a causal link .\nAlso , not all studies demonstrated a positive correlation between inflammatory cytokines and suicidal behavior ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Obesity and type 2 diabetes ( T2D ) are associated with abnormal cardiovascular autonomic function and increased risk for cardiac complications , especially after exercise . Since improvements at rest are not always observed after training , we investigated changes in resting and post-exercise autonomic function in obese women with and without T2D after16-week of walking training . Heart rate ( HR ) variability ( HRV ) and baroreflex sensitivity ( BRS ) were measured at rest and 20 min after a 20 min bout of treadmill exercise at 65 % VO2 peak in obese women with ( n = 8) and without T2D ( n = 12 ) before and after training . HRV was analyzed by frequency-domain [ high- ( HF ) power and low-frequency ( LF ) ] and BRS by the sequence method . Exercise training induced similar significant changes in VO2 peak , resting systolic blood pressure ( SBP ) and post-exercise autonomic function in both groups . Training increased VO2 peak ( 6 % ; P < 0.01 ) and decreased resting SBP ( 8 % ; P < 0.001 ) . Increased post-exercise HR recovery ( 5 % ; P < 0.001 ) , HF power ( 14 % ; P < 0.05 ) , LF power ( 14 % ; P < 0.05 ) and BRS ( 86 % ; P < 0.001 ) were also observed . Resting autonomic function and post-exercise SBP were not altered after training . In conclusion , endurance training reduced blood pressure without changes in HRV and BRS at rest , but training increased HRV and BRS during the recovery of acute endurance exercise indicating an improved post-exercise autonomic modulation of HR , which was similar in obese women with and without T2D Objective To evaluate the effect of 8-week moderate intensity aerobic ( heart-rate reserve 40–60 % ) exercise on neuropathy quality of life in type 2 diabetes . Methods A single blind , parallel-group , r and omized controlled trial was carried out in a tertiary setting . People with type 2 diabetes were eligible for the study if they had clinical neuropathy which was defined by a minimum score of seven on the Michigan diabetic neuropathy score . Following which , the patients were r and omly assigned to an 8-week program by a computer-generated r and om number tables to intervention or control group . Repeated measure analysis of variance was used for data analysis ( p < 0.05 was considered significant ) . Results There were 47 participants in the control group and 40 participants in the study group after r and omization but 37 from the control group and 29 from the intervention group completed the final analysis . The two groups had a significant difference , pre – post intervention in scores of pain ( F = 7 , p = 0.01 ) , sensory symptoms ( F = 4.60 , p = 0.04 ) , restricted activities of daily living ( F = 4.97 , p = 0.03 ) , disruptions in social relationships ( F = 5.43 , p = 0.02 ) , specific impact on quality of life ( F = 9.28 , p < 0.001 ) overall quality of life ( F = 28.72 , p < 0.001 ) , and total score ( F = 31.10 , p < 0.001 ) . Degrees of freedom for all the components were 1 , 62 . Conclusion Moderate intensity aerobic exercise is cornerstone in improving the quality of life of individuals with peripheral neuropathy in type 2 diabetes Background — The Epidemiology of Diabetes Interventions and Complications ( EDIC ) study , a prospect i ve observational follow-up of the Diabetes Control and Complications Trial ( DCCT ) cohort , reported persistent benefit of prior intensive therapy on retinopathy and nephropathy in type 1 diabetes mellitus . We evaluated the effects of prior intensive insulin therapy on the prevalence and incidence of cardiac autonomic neuropathy ( CAN ) in former DCCT intensive and conventional therapy subjects 13 to 14 years after DCCT closeout . Methods and Results — DCCT autonomic measures ( R-R variation with paced breathing , Valsalva ratio , postural blood pressure changes , and autonomic symptoms ) were repeated in 1226 EDIC subjects in EDIC year 13/14 . Logistic regression models were used to calculate the odds of incident CAN by DCCT treatment group after adjustment for DCCT baseline covariates , duration in the DCCT , and quantitative autonomic measures at DCCT closeout . In EDIC year 13/14 , the prevalence of CAN using the DCCT composite definition was significantly lower in the former intensive group versus the former conventional group ( 28.9 % versus 35.2 % ; P=0.018 ) . Adjusted R-R variation was significantly greater in the former DCCT intensive versus the former conventional group ( 29.9 versus 25.9 ; P<0.001 ) . Prior DCCT intensive therapy reduced the risks of incident CAN by 31 % ( odds ratio , 0.69 ; 95 % confidence interval , 0.51 to 0.93 ) and of incident abnormal R-R variation by 30 % ( odds ratio , 0.70 ; 95 % confidence interval , 0.51 to 0.96 ) in EDIC year 13/14 . Conclusions — Although CAN prevalence increased in both groups , the incidence was significantly lower in the former intensive group compared with the former conventional group . The benefits of former intensive therapy extend to measures of CAN up to 14 years after DCCT closeout BACKGROUND Post-trial monitoring of patients in the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) examined whether risk reductions for microvascular and macrovascular disease , achieved with the use of improved blood-pressure control during the trial , would be sustained . METHODS Among 5102 UKPDS patients with newly diagnosed type 2 diabetes mellitus , we r and omly assigned , over a 4-year period beginning in 1987 , 1148 patients with hypertension to tight or less-tight blood-pressure control regimens . The 884 patients who underwent post-trial monitoring were asked to attend annual UKPDS clinics for the first 5 years , but no attempt was made to maintain their previously assigned therapies . Annual question naires completed by patients and general practitioners were used to follow patients who were unable to attend the clinic in years 1 through 5 , and question naires were used for all patients in years 6 to 10 . Seven prespecified aggregate clinical end points were examined on an intention-to-treat basis , according to the previous r and omization categories . RESULTS Differences in blood pressure between the two groups during the trial disappeared within 2 years after termination of the trial . Significant relative risk reductions found during the trial for any diabetes-related end point , diabetes-related death , microvascular disease , and stroke in the group receiving tight , as compared with less tight , blood-pressure control were not sustained during the post-trial follow-up . No risk reductions were seen during or after the trial for myocardial infa rct ion or death from any cause , but a risk reduction for peripheral vascular disease associated with tight blood-pressure control became significant ( P=0.02 ) . CONCLUSIONS The benefits of previously improved blood-pressure control were not sustained when between-group differences in blood pressure were lost . Early improvement in blood-pressure control in patients with both type 2 diabetes and hypertension was associated with a reduced risk of complications , but it appears that good blood-pressure control must be continued if the benefits are to be maintained . ( UKPDS 81 ; Current Controlled Trials number , IS RCT N75451837 . Objective : To test the hypothesis that 12 months of seal oil omega-3 polyunsaturated fatty acids ( ω-3 PUFA ) supplementation will stop the known progression of diabetic sensorimotor polyneuropathy ( DSP ) in type 1 diabetes mellitus ( T1DM ) . Methods : Individuals with T1DM and evidence of DSP as determined by a Toronto Clinical Neuropathy Score ≥1 were recruited to participate in a single-arm , open-label trial of seal oil ω-3 PUFA supplementation ( 10 mL·d−1 ; 750 mg eicosapentaenoic acid , 560 mg docosapentaenoic acid , and 1,020 mg docosahexaenoic acid ) for 1 year . The primary outcome was the 1-year change in corneal nerve fiber length ( CNFL ) measured by in vivo corneal confocal microscopy , with sensory and nerve conduction measures as secondary outcomes . Results : Forty participants ( 53 % female ) , aged 48 ± 14 years , body mass index 28.1 ± 5.8 with diabetes duration of 27 ± 18 years , were enrolled . At baseline , 23 participants had clinical DSP and 17 did not . Baseline CNFL was 8.3 ± 2.9 mm/mm2 and increased 29 % to 10.1 ± 3.7 mm/mm2 ( p = 0.002 ) after 12 months of supplementation . There was no change in nerve conduction or sensory function . Conclusions : Twelve months of ω-3 supplementation was associated with increase in CNFL in T1DM . Clinical Trials.govidentifier : NCT02034266 . Classification of evidence : This study provides Class IV evidence that for patients with T1DM and evidence of DSP , 12 months of seal oil omega-3 supplementation increases CNFL BACKGROUND Diabetes is the most important cause of peripheral neuropathy ( DPN ) . No definitive treatment for DPN has been established , and very few data on the role of exercise training on DPN have been reported . AIM OF THE STUDY We sought to examine the effects of long-term exercise training on the development of DPN in both Types 1 and 2 diabetic patients . PARTICIPANTS AND METHODS Seventy-eight diabetic patients without signs and symptoms of peripheral DPN were enrolled , r and omized , and subdivided in two groups : 31 diabetic participants [ 15 f , 16 m ; 49+/-15.5 years old ; body mass index ( BMI ) = 27.9+/-4.7 ] , who performed a prescribed and supervised 4 h/week brisk walking on a treadmill at 50 % to 85 % of the heart rate reserve ( exercise group : EXE ) , and a control group of 47 diabetic participants ( CON ; 24 f , 23 m ; 52.9+/-13.4 years old ; BMI = 30.9+/-8.4 ) . Vibration perception threshold ( VPT ) , nerve distal latency ( DL ) , nerve conduction velocity ( NCV ) , and nerve action potential amplitude ( NAPA ) in the lower limbs were measured . RESULTS We found significant differences on Delta ( delta ) in NCV for both peroneal and sural motor nerve between the EXE and CON groups during the study period ( P<.001 , for both ) . The percentage of diabetic patients that developed motor neuropathy and sensory neuropathy during the 4 years of the study was significantly higher in the CON than the EXE group ( 17 % vs. 0.0 % , P<.05 , and 29.8 % vs. 6.45 % , P<.05 , respectively ) . In addition , the percentage of diabetic patients who developed increased VPT ( 25 V ) during the study was significantly higher in the CON than the EXE group ( 21.3 % vs. 12.9 % , P<.05 ) . Change on Hallux VPT from baseline to the end of the study was significantly different between the EXE and CON groups ( P<.05 ) ; no significant change in Malleolus VPT between the two groups occurred . CONCLUSIONS This study suggests , for the first time , that long-term aerobic exercise training can prevent the onset or modify the natural history of DPN OBJECTIVE To evaluate the efficacy and safety of α-lipoic acid ( ALA ) over 4 years in mild-to-moderate diabetic distal symmetric sensorimotor polyneuropathy ( DSPN ) . RESEARCH DESIGN AND METHODS In a multicenter r and omized double-blind parallel-group trial , 460 diabetic patients with mild-to-moderate DSPN were r and omly assigned to oral treatment with 600 mg ALA once daily ( n = 233 ) or placebo ( n = 227 ) for 4 years . Primary end point was a composite score ( Neuropathy Impairment Score [NIS]–Lower Limbs [ NIS-LL ] and seven neurophysiologic tests ) . Secondary outcome measures included NIS , NIS-LL , nerve conduction , and quantitative sensory tests ( QSTs ) . RESULTS Change in primary end point from baseline to 4 years showed no significant difference between treatment groups ( P = 0.105 ) . Change from baseline was significantly better with ALA than placebo for NIS ( P = 0.028 ) , NIS-LL ( P = 0.05 ) , and NIS-LL muscular weakness subscore ( P = 0.045 ) . More patients showed a clinical ly meaningful improvement and fewer showed progression of NIS ( P = 0.013 ) and NIS-LL ( P = 0.025 ) with ALA than with placebo . Nerve conduction and QST results did not significantly worsen with placebo . Global assessment of treatment tolerability and discontinuations due to lack of tolerability did not \n Output:\n " }, { "from": "agent", "value": "Conclusions Recent research indicates that dietary interventions are effective in modifying diabetic neuropathy in animal models , and there are promising data that they may also ameliorate diabetic neuropathy in humans .\nHowever , there is emerging evidence that lifestyle interventions are effective in individuals with established diabetic neuropathy .\nIn addition to the observed clinical value of lifestyle interventions , there is emerging evidence of effects on biochemical pathways that improve muscle function and affect other organ systems , including the peripheral nerve ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: The objective of this double-blind clinical study was to compare the tooth whitening efficacy ( stain removal ) of a new commercially available tooth whitening dentifrice ( Colgate Total Plus Whitening Toothpaste ) containing 0.2 % triclosan and 3.0 % PVM/MA copolymer in a 0.243 % sodium fluoride/high cleaning silica base , with that of two commercially available dentifrices , Crest Multi-Care Advanced Cleaning Toothpaste and Colgate Winterfresh Gel Fluoride Toothpaste . Following a baseline examination to assess extrinsic tooth stain , qualifying adult male and female subjects were r and omized into three treatment groups which were balanced for gender , age and level of extrinsic tooth stain . Subjects were asked to brush their teeth twice ( morning and evening ) for one minute with their assigned dentifrice using a soft-bristled toothbrush . Examinations for extrinsic tooth stain were repeated after six weeks ' use of the study dentifrices . One-hundred and twenty-three ( 123 ) subjects complied with the protocol and completed the study . At the six-week examination , subjects assigned to the Colgate Total Plus Whitening Toothpaste treatment group exhibited statistically significant reductions in extrinsic tooth stain area and extrinsic tooth stain intensity relative to those subjects assigned to the Crest Multi-Care Advanced Cleaning Toothpaste and the Colgate Winterfresh Gel Fluoride Toothpaste The objective of this double-blind clinical study was to investigate the tooth whitening efficacy of a new commercially available calculus-inhibiting dentifrice ( Colgate Tartar Control Plus Whitening Fluoride dentifrice ) containing tetra-sodium pyrophosphate , sodium tripolyphosphate , and PVM/MA copolymer in a 0.243 % sodium fluoride/silica base ( test dentifrice ) , compared to a commercially available , non-tooth whitening dentifrice containing 0.243 % sodium fluoride in a silica base ( control dentifrice ) . Following a baseline examination for , extrinsic tooth stain , qualifying adult male and female subjects from the Manchester , United Kingdom area were r and omized into two treatment groups which were balanced for gender , age and level of extrinsic tooth stain . Subjects were instructed to brush their teeth twice daily ( morning and evening ) for one minute with their assigned dentifrice using a soft-bristled toothbrush . Examinations for extrinsic tooth stain were repeated after six weeks ' use of the study dentifrices . Seventy-nine(79 ) subjects complied with the protocol and completed the entire study . At the six-week examination , subjects assigned to the test dentifrice treatment group exhibited statistically significant reductions of over 40 % with respect to both extrinsic tooth stain area and extrinsic tooth stain intensity relative to those subjects assigned to the control dentifrice treatment group The objective of this double-blind clinical study was to compare the efficacy for extrinsic tooth stain removal of four commercially available dentifrices : Colgate Tartar Control with Baking Soda & Peroxide Fluoride Toothpaste ; Aquafresh Advanced Whitening Toothpaste with Fluoride ; Rembr and t Tartar Control Low Abrasion Fluoride Whitening Toothpaste ; and Crest Regular Fluoride Toothpaste . Following a baseline examination for extrinsic tooth stain on the anterior six m and ibular and maxillary teeth , qualifying adult male and female subjects from the Philadelphia , Pennsylvania area were r and omized into four treatment groups which were balanced for age , gender , tobacco habits , and level of extrinsic tooth stain . Subjects were instructed to brush their teeth twice daily ( morning and evening ) for one minute with their assigned dentifrice using a soft-bristled toothbrush . Examinations for extrinsic tooth stain were repeated after six weeks ' use of the study dentifrices . One hundred eighty ( 180 ) subjects complied with the protocol , and completed the entire study . At the six-week examination , subjects assigned to the Colgate Tartar Control with Baking Soda & Peroxide Fluoride Toothpaste treatment group exhibited statistically lower levels of extrinsic tooth stain area and extrinsic tooth stain intensity than did those subjects assigned to the Crest Regular Fluoride treatment group . Subjects assigned to the Aquafresh Advanced Whitening treatment group exhibited significantly lower levels of extrinsic tooth stain area than did those assigned the Crest Regular Fluoride group . No other significant differences among the four study dentifrices were noted . Thus , the results of this double-blind clinical study support the conclusion that Colgate Tartar Control with Baking Soda & Peroxide Fluoride Toothpaste provides significantly greater control of extrinsic tooth stain than does Crest Regular Fluoride , a sodium fluoride/silica dentifrice OBJECTIVE The objective of this clinical investigation was to evaluate the effectiveness in removing existing extrinsic tooth stains of a sodium bicarbonate ( baking soda ) , dual-phase dentifrice containing calcium and phosphate ( Test Dentifrice ) , when compared to a commercial hydrated silica dentifrice ( Control Dentifrice ) , during a six-week period of normal , unsupervised use . METHODOLOGY This investigation was a double-blind comparison of two equivalent , parallel groups of subjects assigned to use different dentifrices for six weeks . A total of 108 adult male and female subjects qualified for the trial based on the presence of existing extrinsic tooth stains and other inclusion /exclusion criteria . The two groups were balanced for gender , tobacco use , and extrinsic tooth stain scores , and r and omly assigned the Test or Control dentifrices . All subjects were instructed to brush their teeth twice daily using only the dentifrice and toothbrush provided , and to refrain from using any other oral hygiene products for the duration of the study . Although product usage was unsupervised after the baseline visit , subjects maintained a treatment diary , and product consumption was monitored to estimate compliance . Oral soft and hard tissue and extrinsic stain assessment s ( Modified Lobene Stain Index ) for each subject were conducted at baseline and after two , four , and six weeks of product use . RESULTS A total of 107 subjects complied with the protocol and completed the six-week study . Compared to baseline , at the two- , four- , and six-week examinations the Test Dentifrice group had statistically significant reductions in extrinsic tooth stain . In contrast , the Control Dentifrice group did not attain significant reductions from baseline at any of the exams . At both the four-week and six-week examinations , the Test Dentifrice group had significantly lower levels of extrinsic tooth stain than the Control Dentifrice group . CONCLUSION A sodium bicarbonate , dual-phase dentifrice containing calcium and phosphate demonstrated statisically significant efficacy in removing naturally acquired , extrinsic tooth stain , and was significantly more effective for stain removal than a commercially available , hydrated silica dentifrice The effect of twice-daily brushing with one of three different dentifrices ( Arm & Hammer Dental Care , Arm & Hammer Dental Care Extra Whitening , Crest ) on stain removal and tooth whitening was examined in 115 volunteers over a period of 12 weeks . The facial surfaces of 12 anterior teeth were assessed for stain using a published , modified version of a st and ard stain index . Whiteness was measured on teeth 8 and 9 using a single Vita Lumin-Vaccum Shade Guide for consistency . At baseline , the mean facial stain scores were significantly higher ( p < 0.05 - 0.01 ) for both Arm & Hammer dentifrices than for Crest . In addition , the tooth shades , as indicated by the stain guide , specifically the b * values representing yellowness , were quantified using a Minolta spectrophotometer . Arm & Hammer Dental Care Extra Whitening formula was found to be significantly better than Crest at removing naturally occurring extrinsic stain . The difference between Arm & Hammer Dental Care Extra Whitening and Crest became significant ( p < 0.01 ) after two weeks of use , and remained intact during the balance of the study , achieving p values of 0.0002 for at least one of the three assessed parameters ( total stain , proximal , and facial ) at weeks 4 and 12 . The study also found that Arm & Hammer Dental Care produced a significant increase in tooth whiteness by week 12 , whereas Crest showed no such increase at any time during the study . These results suggest that the two Arm & Hammer Baking Soda products are more effective in reducing stain and increasing whiteness than the st and ard silica-based dentifrice . Their effectiveness is not related to abrasivity since they are less abrasive to tooth enamel than the silica-based product tested OBJECTIVES To evaluate a modified tooth stain index and determine the effect of dietary factors on stain formation . METHODS At baseline , 182 adult volunteers were given a full oral prophylaxis followed by stain assessment using a modification of the Lobene index . This involved assigning separate scores to the mesial ( M ) and distal ( D ) sites of each tooth , in addition to the st and ard gingival area ( G ) and tooth body ( B ) . For each site , stain intensity and areas were scored . The sum of ( intensity X area ) scores was calculated for all sites ( GBMD-value ) and for the gingival and body sites only ( GB-value ) . The subjects used a st and ard abrasive dentifrice and a soft toothbrush for 6 weeks . RESULTS Stain was reassessed and the average increase in GBMD-value was 20.9 ( sd=9.9 ) ( buccal aspect ) and 29.9 ( sd=18.0 ) ( lingual aspect ) . The corresponding GB-values were 4.4 ( sd=4.8 ) and 12.5 ( sd=10.2 ) . The coefficients of variation of the GBMD index values were consistently lower than those of the GB values . Smoking and tea-drinking were found to be the only significant ( p<0.001 ) factors investigated for stain formation . CONCLUSIONS It is concluded that the modified index may well be advantageous to its conventional counterpart because sites with most visible stain are assessed separately and because it may also offer higher discriminatory power due to a lower coefficient of variation OBJECTIVE The primary purpose of this r and omized , controlled , six-week clinical trial was to determine the effectiveness and safety of a new whitening dentifrice in removing extrinsic tooth stain and whitening teeth . An additional two-week exploratory study was conducted to determine whether the whitening or stain-prevention activity of the dentifrice would persist following cessation of use . METHODS In the first study ( Phase I ) , one-hundred and forty-six qualifying subjects were r and omly assigned to either a sodium bicarbonate whitening dentifrice group ( Arm & Hammer Advance White Extreme Whitening Baking Soda and Peroxide Toothpaste ) or a silica-based negative control dentifrice group , and brushed twice daily with their assigned dentifrice for six weeks . Tooth shade on the labial surfaces of the eight incisors was assessed using a Vita Classic shade guide , and extrinsic tooth stain was scored using a Modified Lobene Stain Index ( MLSI ) at baseline , week 4 , and week 6 . In Phase II ( after the week 6 examination ) , volunteers from the Arm & Hammer whitening dentifrice group were r and omly assigned to continue using the whitening dentifrice or to use the negative control dentifrice twice daily for two weeks . The six-week shade and stain index scores served as the baseline for this exploratory phase and were rescored after two weeks . RESULTS The whitening dentifrice group had statistically significant ( p < 0.0001 ) mean shade score reductions of 1.82 and 2.57 from baseline to weeks 4 and 6 , respectively . For the same periods , the negative control dentifrice group was virtually unchanged from baseline . For tooth stain , the MLSI total mean scores for the whitening dentifrice group showed statistically significant ( p < 0.0001 ) decreases from baseline of 1.42 ( 41.6 % ) and 2.11 ( 61.6 % ) at weeks 4 and 6 , respectively . In contrast , the negative control dentifrice group had a MLSI reduction of 0.07 at week 4 and a 0.06 increase at week 6 . Between-group analyses using baseline-adjusted ANCOVA showed the whitening dentifrice to be statistically significantly more effective ( p < 0.0001 ) than the negative control for shade and tooth stain reductions for all index comparisons . Compared to the six-week ( baseline ) scores , subjects who continued to use the whitening dentifrice for the additional two weeks experienced statistically significant ( p < 0.0001 ) further mean reductions of 0.88 in shade score and 0.46 in MLSI score , while subjects who switched to the negative control dentifrice experienced smaller , statistically significant ( p < 0.05 ) reductions of 0.34 in shade score and 0.13 in total MLSI score . CONCLUSION The Arm & Hammer whitening dentifrice tested in this study is effective for removing extrinsic tooth stain and whitening teeth . While the results also suggest that this dentifrice may have stain-prevention activity that persists following cessation of product use , such activity would need to be confirmed with further studies The objective of this double-blind clinical study was to investigate the tooth whitening efficacy of a new dentifrice ( Colgate Tartar Control Plus Whitening Fluoride Toothpaste ) for the removal of extrinsic tooth stain , through a comparison with two commercially available dentifrices , Aquafresh Whitening Toothpaste with Fluoride , and Crest Regular Fluoride Toothpaste . Following a baseline examination for extrinsic tooth stain area and intensity , qualifying adult male and female subjects from the Mississauga , Ontario , Canada area were r and omized into three treatment groups which were balanced for age , gender , and level of extrinsic to \n Output:\n " }, { "from": "agent", "value": "In this review , nearly all dentifrices that are specifically formulated for tooth whitening were shown to have a beneficial effect in reducing ETD , irrespective of whether or not a chemical discoloration agent was added" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Background Fatigue or lack of interest can reduce the feasibility of intensive physical exercise in nursing home residents . Low-volume exercise interventions with similar training effects might be an alternative . The aim of this r and omised controlled trial was to investigate the feasibility of Whole Body Vibration ( WBV ) in institutionalised elderly , and its impact on functional capacity and muscle performance . Methods Twenty-four nursing home residents ( 15 female , 9 male ; mean age 77.5 ± 11.0 years ) were r and omised ( stratification for age , gender and ADL-category ) to 6 weeks static WBV exercise ( WBV+ , N = 13 ) or control ( only static exercise ; N = 11 ) . Outcome measures were exercise compliance , timed up- and -go , Tinetti-test , back scratch , chair sit- and -reach , h and grip strength and linear isokinetic leg extension . Results At baseline , WBV+ and control groups were similar for all outcome variables . Twenty-one participants completed the program and attended respectively 96 % and 86 % of the exercise sessions for the WBV+ and control groups . Training-induced changes in timed up- and -go and Tinetti-test were better for WBV+ compared to control ( p = 0.029 for timed up- and -go , p = 0.001 and p = 0.002 for Tinetti body balance and total score respectively ) . In an alternative analysis ( Worst Rank Score & Last Observation Carried Forward ) the differences in change remained significant on the Tinetti body balance and total score . No other significant differences in change between both groups were observed . Conclusion In nursing home residents with limited functional dependency , six weeks static WBV exercise is feasible , and is beneficial for balance and mobility . The supplementary benefit of WBV on muscle performance compared to classic exercise remains to be explored further OBJECTIVE To use two different exercise programs over a 2-year period to reduce falls and their sequelae among residents of two long-term care facilities . DESIGN R and omized , controlled trial . SETTING The study took place at two long-term care facilities with services ranging from independent living to skilled nursing . PARTICIPANTS One hundred and ten participants whose average age was 84 and who were capable of ambulating with or without assistive devices and could follow simple directions . INTERVENTION Participants were r and omized to one of two exercise groups ( resistance/endurance plus basic enhanced programming or tai chi plus basic enhanced programming ) or to a control group ( basic enhanced programming only ) . Exercise classes were held three times per week throughout the study . MEASUREMENTS Participants were evaluated for cognitive and physical functioning at baseline and 6 , 12 , and 24 months . Falls were determined from incident reports filed by the nursing staffs at the facilities . RESULTS Time to first fall , time to death , number of days hospitalized , and incidence of falls did not differ among the treatment and control groups ( P>.05 ) . Among all participants , those who fell had significantly lower baseline Folstein Mini-Mental State Examination and instrumental activities of daily living scores and experienced significantly greater declines in these measures over the 2-year program . CONCLUSION There were no significant differences in falls among the two exercise groups and the control group . Lack of treatment differences and low adherence rates suggest that residents of long-term care facilities may require individualized exercise interventions that can be adapted to their changing needs This paper describes a quasi-experimental study of a musical exercise intervention to improve the physical , cognitive , behavioral status and life satisfaction of older residents in a long-term care facility in the United Kingdom . Twenty long-term care residents from three different units ( n=60 ) were recruited and assigned to one of three groups : a control ( C ) group ( no intervention ) , an occupational therapy ( OT ) group ( comparison group ) and a music exercise group ( intervention group ) . Assessment s of physical and cognitive status were made pre-intervention and repeated at the end of the 10-week exercise program and again 10 weeks after the completion of the program . The results show that both OT and exercise participation is associated with improvement in physical and cognitive function . However , the exercise group showed significant improvement in more areas than the OT group . The functional benefits from OT and exercise were not sustainable after these activities ceased and showed significant decline 10 weeks after the end of the programs OBJECTIVES To establish the effectiveness of a fall-prevention program in reducing falls and injurious falls in older residential care residents . DESIGN Cluster , r and omized , controlled trial . SETTING Fourteen r and omly selected residential care homes in Auckl and , New Zeal and . PARTICIPANTS All older residents ( n=628 , 95 % participation rate ) . INTERVENTION Residential care staff , using existing re sources , implemented systematic individualized fall-risk management for all residents using a fall-risk assessment tool , high-risk logo , and strategies to address identified risks . MEASUREMENTS Number of residents sustaining a fall , falls , and injurious-falls incidence rates . RESULTS During 12 months of follow-up , 103 ( 43 % ) residents in the control group and 173 ( 56 % ) residents in the intervention group fell ( P<.018 ) . There was a significantly higher incidence rate of falls in intervention homes than in control homes ( incident rate ratio=1.34 , 95 % confidence interval=1.06 - 1.72 ) during the intervention period after adjusting for dependency level ( type of home ) , baseline fall rate , and clustering . There was no difference in the injurious fall incidence rate or incidence of serious injuries . CONCLUSION This fall-prevention intervention did not reduce falls or injury from falls . Low-intensity intervention may be worse than usual care OBJECTIVE to determine the effect of risk factor modification and balance exercise on falls rates in residential care homes . DESIGN cluster r and omised controlled trial . PARTICIPANTS 196 residents ( aged 60 years or over ) in 20 residential care homes were enrolled ( 38 % response rate ) . Homes were r and omly allocated to intervention and control arms . A total of 102 residents were consigned to the intervention arm and 94 to the control arm . INTERVENTION a multifactorial falls prevention programme including 3 months gait and balance training , medication review , podiatry and optometry . MAIN OUTCOME MEASURES number of falls/recurrent falls per person , number of medications per person , and change in Tinetti gait and balance measure . RESULTS in the intervention group there was a mean of 2.2 falls per resident per year compared with 4.0 in the control group ; this failed to reach statistical significance ( P = 0.2 ) once the intra-cluster correlation ( ICC , 0.10 ) had been accounted for . Several risk factors were reduced in the intervention arm . CONCLUSIONS falls risk factor reduction is possible in residents of care homes . A modest reduction in falls rates was demonstrated but this failed to reach statistical significance Many studies have documented the effectiveness of verbally elicited imagery in the enhancement of motor skills in young , nondisabled population s. The present study examined the effects of verbally elicited imagery in the encouragement of two exercises ( i.e. , reaching up to pick apples and reaching down to pick up coins ) in elderly women . The subjects were 27 women between 62 and 96 years of age who were selected from a nursing home , a residential retirement home , and a foster care home . All of the subjects received imagery as well as control conditions , but in a counterbalanced fashion . The Wilcoxon matched-pairs signed rank tests indicated that the imagery condition elicited significantly more repetitions of the reaching-up exercise than did the control condition ( z = 2.25 , p [ one-tailed ] = .012 ) . The results in the reaching-down exercise were generally in the same direction but difficult to interpret statistically . The results are discussed in terms of other recent research investigating ways to add purpose to therapeutic exercise through occupation . Clinicians are urged to explore the advantages and disadvantages of imagery-based occupations in treatment The aims of this r and omised controlled trial were to determine if a high-intensity functional exercise program improves balance , gait ability , and lower-limb strength in older persons dependent in activities of daily living and if an intake of protein-enriched energy supplement immediately after the exercises increases the effects of the training . One hundred and ninety-one older persons dependent in activities of daily living , living in residential care facilities , and with a Mini-Mental State Examination ( MMSE ) score of ? 10 participated . They were r and omised to a high-intensity functional exercise program or a control activity , which included 29 sessions over 3 months , as well as to protein-enriched energy supplement or placebo . Berg Balance Scale , self-paced and maximum gait speed , and one-repetition maximum in lower-limb strength were followed-up at three and six months and analysed by 2 x 2 factorial ANCOVA , using the intention-to-treat principle . At three months , the exercise group had improved significantly in self-paced gait speed compared with the control group ( mean difference 0.04 m/s , p = 0.02 ) . At six months , there were significant improvements favouring the exercise group for Berg Balance Scale ( 1.9 points , p = 0.05 ) , self-paced gait speed ( 0.05 m/s , p = 0.009 ) , and lower-limb strength ( 10.8 kg , p = 0.03 ) . No interaction effects were seen between the exercise and nutrition interventions . In conclusion , a high-intensity functional exercise program has positive long-term effects in balance , gait ability , and lower-limb strength for older persons dependent in activities of daily living . An intake of protein-enriched energy supplement immediately after the exercises does not appear to increase the effects of the training OBJECTIVES To evaluate the effectiveness of a multifaceted , nonpharmaceutical intervention on incidence of falls and fallers . DESIGN Prospect i ve , cluster-r and omized , controlled 12-month trial . SETTING Six community nursing homes in Germany . PARTICIPANTS Long-stay residents ( n = 981 ) aged 60 and older ; mean age 85 ; 79 % female . INTERVENTIONS Staff and resident education on fall prevention , advice on environmental adaptations , progressive balance and resistance training , and hip protectors . MEASUREMENTS Falls , fallers , and fractures . RESULTS The incidence density rate of falls per 1,000 resident years ( RY ) was 2,558 for the control group ( CG ) and 1,399 for the intervention group ( IG ) ( relative risk ( RR ) = 0.55 , 95 % confidence interval ( CI ) = 0.41 - 0.73 ) . Two hundred forty-seven ( 52.3 % ) fallers were detected in the CG and 188 ( 36.9 % ) in the IG ( RR = 0.75 , 95 % CI = 0.57 - 0.98 ) . The incidence density rate of frequent fallers ( > 2/year ) was 115 ( 24.4 % ) for the CG and 66 ( 13.0 % ) for the IG ( RR = 0.56 , 95 % CI = 0.35 - 0.89 ) . The incidence density rate of hip fractures per 1,000 RY was 39 for the CG and 43 for the IG ( RR = 1.11 , 95 % CI = 0.49 - 2.51 ) . Other fractures were diagnosed with an incidence density rate of 52 per 1,000 RY for CG and 41 per 1,000 RY for IG ( RR = 0.78 , 95 % CI = 0.57 - 1.07 ) . CONCLUSION The incidence density rate of falls and fallers differed considerably between the control and intervention groups . The study was underpowered to demonstrate a significant difference of hip or nonhip fractures . Because of a low fracture rate in both groups , the investigation of fracture rates would have required a larger sample size to detect an effect of the intervention Abstract A r and omised controlled trial was undertaken to measure effects of exercise on : 1 . Progression of cognitive symptoms related to dementia using the Clock-Drawing Test ( Shulman et al. 1993 ) ; and 2 . Disability using the Revised Elderly Persons Disabilities Scale ( REPDS ; Fleming and Bowles 1993 ) . Data was analysed from 75 nursing home residents with dementia who were r and omly assigned to one experimental group and two control groups . Group 1 ( control ) received no intervention . Group 2 ( control ) received a social visit equivalent in duration and frequency as those undertaking the exercise program in the experimental group , Group 3 . A specifically design ed , frail aged appropriate , twelve-week exercise program was undertaken by the those in the experimental group three times per week . Each session lasted for 30 minutes . Findings from the : 1 . Clock-drawing test showed that exercise may slow the rate of progression of the cognitive symptoms related to dementia ; and 2 . REPDS showed that exercise slowed and reversed disability in some of the activities of daily living One of the effects of Alzheimer 's disease is a diminution in the ability to communicate . A r and omized , non-blinded two-group experimental study was undertaken to determine if planned walking has the capacity to improve the communication performance of patients with moderate to severe Alzheimer 's disease . Thirty subjects meeting NINCDS-ADRDA diagnostic criteria for probable Alzheimer 's disease , selected from two nursing homes , participated in the study . Intervention and comparison groups were each made up of subjects from both nursing homes . Subjects in one group were walked individually for 30 minutes three times a week for 10 weeks . Subjects in the comparison group were engaged in conversation for the same amount of time for 10 weeks . A multivariate analysis of variance ( MANOVA ) was performed on the communication data . \n Output:\n " }, { "from": "agent", "value": "Provision of physical rehabilitation interventions to long-term care residents is worthwhile and safe , reducing disability with few adverse events .\nMost trials reported improvement in physical condition .\nHowever , there is insufficient evidence to make recommendations about the best intervention , improvement sustainability and cost-effectiveness" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Introduction We have assessed the utility of autologous mesenchymal stem cell ( MSC ) peripheral vein infusion as a possible therapeutic modality for patients with end-stage liver diseases . Methods Forty patients with post-hepatitis C virus ( HCV ) end-stage liver disease were r and omized into two groups : Group 1 ( GI ) : 20 patients who received granulocyte colony-stimulating factor ( G-CSF ) for 5 days followed by autologous MSCs peripheral-vein infusion and group 2 ( GII ) : 20 patients who received regular liver-supportive treatment only ( control group ) . Results In MSC-infused patients ( GI ) , 54 % showed near normalization of liver enzymes and improvement in liver synthetic function . Significant changes were reported in albumin ( P = 0.000 ) , bilirubin ( P = 0.002 ) , increased international normalized ratio ( INR ) ( P = 0.017 ) , prothrombin concentration ( P = 0.029 ) and alanine transaminase ( ALT ) levels ( P = 0.029 ) , with stabilization of clinical and biochemical status in 13 % of cases . None of the patients in GII showed any significant improvement . Hepatic fibrosis was assessed in GI by detection of procollagen IIIC peptide level ( PIIICP ) and procollagen III N peptide level ( PIIINP ) . The pretreatment values of s-PIIICP and s-PIIINP were 9.4 ± 4.2 and 440 ± 189 , respectively , with a decrease to 8.1 ± 2.6 and 388 ± 102 , respectively , 3 months after MSC therapy . However , the difference was statistically nonsignificant ( P = 0.7 ) . A significant correlation coefficient was reported after 3 months between the s-PIIINP and prothrombin concentration ( P = -0.5 ) and between s-PIIICP and ascites ( P = 0.550 ) . Conclusions First , autologous MSC infusion into a peripheral vein is as effective as the previously reported intrahepatic infusion . Second , MSCs have a supportive role in the treatment of end-stage liver disease , with satisfactory tolerability and beneficial effects on liver synthetic functions and hepatic fibrosis . Third , IV infusion of MSCs after G-CSF mobilization improves s-albumin within the first 2 weeks and prothrombin concentration and alanine Taransaminase after 1 month . According to the data from this current study and those previously reported by our group , we recommend further studies on patients ’ infusion with pure CD133 and CD34 followed by IV infusion of in vitro-differentiated MSCs within 1 week and another infusion after 3 months . Trial registration Clinical Trials.gov NCT01729221 . Registered 17 November 2012 BACKGROUND The st and ard treatment for decompensated liver cirrhosis is liver transplantation . However , it has several limitations . Recent animal studies suggest that bone marrow stem cell transplantation can lead to regression of liver fibrosis . The objective of this study was to determine the safety and feasibility of autologous bone marrow-mesenchymal stem cell transplantation in patients with decompensated liver cirrhosis . METHODS In this phase 1 trial , four patients with decompensated liver cirrhosis were included . Their bone marrow was aspirated , mesenchymal stem cells were cultured , and a mean 31.73 x 10(6 ) mesenchymal stem cells were infused through a peripheral vein . Primary outcomes were evaluating the safety and feasibility of the work . Secondary outcomes were evaluating changes in the model for end-stage liver disease score , and the quality of life of the patients . RESULTS There were no side-effects in the patients during follow-up . The model for end-stage liver disease scores of patients 1 , and 4 improved by four and three points , respectively by the end of follow-up . Furthermore , the quality of life of all four patients improved by the end of follow-up . Using SF-36 question naire , the mean physical component scale increased from 31.44 to 65.19 , and the mean mental component scale increased from 36.32 to 65.55 . CONCLUSION Mesenchymal stem cell transplantation seems to be feasible and safe in the treatment of decompensated liver cirrhosis The study was aim ed to evaluate the effect of autologous transplantation of BM-derived undifferentiated and differentiated MSCs in cirrhotic patients following chronic hepatitis C virus infection . Twenty-five patients with Child C liver cirrhosis , MELD score > 12 were included . They were divided into 2 groups . Group I , the MSCs group ( n = 15 ) , this group was subdivided into two subgroups : Ia & Ib ( undifferentiated and differentiated respectively ) . Group II ( control group ; n = 10 ) involved patients with cirrhotic liver under conventional supportive treatment . Ninety ml BM was aspirated from the iliac bone for separation of MSCs . Surface expression of CD271 , CD29 and CD34 were analyzed using flowcytometry . Hepatogenesis was assessed by immunohistochemical expression of OV6 , AFP and albumin . Finally approximately 1 million MSCs/Kg were suspended in saline and were placed in blood bag and injected slowly intravenously over 15 min at a rate of 5 drops/min in one session . Follow up of patients at 3 and 6 months postinfusion revealed partial improvement of liver function tests with elevation of prothrombin concentration and serum albumin levels , decline of elevated bilirubin and MELD score in MSCs group . Statistical comparisons between the two subgroups ( group Ia & Ib ) did not merit any significant difference regarding clinical and laboratory findings . In conclusion : Bone marrow MSCs transplantation either undifferentiated or differentiated can be used as a potential treatment for liver cirrhosis The objective of this study was to evaluate the safety and efficacy of allogeneic bone marrow mesenchymal stromal/stem cell transplantation ( BM-MSCT ) for patients with ursodeoxycholic acid (UDCA)-resistant primary biliary cirrhosis ( PBC ) . Ten patients were enrolled in this trial of BM-MSCT . All patients were permitted to concurrently continue their previous UDCA treatment . The efficacy of BM-MSCT in UDCA-resistant PBC was assessed at various time points throughout the 12-month follow up . No transplantation-related side effects were observed . The life quality of the patients was improved after BM-MSCT as demonstrated by responses to the PBC-40 question naire . Serum levels of ALT , AST , γ-GT , and IgM significantly decreased from baseline after BM-MSCT . In addition , the percentage of CD8 + T cells was reduced , while that of CD4+CD25+Foxp3 + T cells was increased in peripheral lymphocytic subsets . Serum levels of IL-10 were also elevated . Notably , the optimal therapeutic outcome was acquired in 3 to 6 months and could be maintained for 12 months after BM-MSCT . In conclusion , allogeneic BM-MSCT in UDCA-resistant PBC is safe and appears to be effective BACKGROUND In experimental models , bone marrow-derived mesenchymal stem cells ( BM-MSCs ) have the capacity to differentiate into hepatocytes and exhibit antifibrotic effects . However , there have been no studies in humans with alcoholic cirrhosis . AIM The aim of this study was to eluci date the antifibrotic effect of BM-MSCs in patients with alcoholic cirrhosis , as a phase II clinical trial . METHODS Twelve patients ( 11 males , 1 female ) with baseline biopsy-proven alcoholic cirrhosis who had been alcohol free for at least 6 months were enrolled . BM-MSCs were isolated from each patient 's BM and amplified for 1 month , and 5 × 10(7 ) cells were then injected twice , at weeks 4 and 8 , through the hepatic artery . One patient was withdrawn because of ingestion of alcohol . Finally , 11 patients completed the follow-up biopsy and laboratory tests at 12 weeks after the second injection . The primary outcome was improvement in the patients ' histological features . RESULTS According to the Laennec fibrosis system , histological improvement was observed in 6 of 11 patients ( 54.5 % ) . The Child-Pugh score improved in ten patients ( 90.9 % ) and the levels of transforming growth factor-β1 , type 1 collagen and α-smooth muscle actin significantly decreased ( as assessed by real-time reverse transcriptase polymerase chain reaction ) after BM-MSCs therapy ( P < 0.05 ) . No significant complications or side effects were observed during this study . CONCLUSIONS Bone marrow-derived mesenchymal stem cells therapy in alcoholic cirrhosis induces a histological and quantitative improvement of hepatic fibrosis BACKGROUND & AIMS There has been great interest in recent years to take advantage of bone marrow stem cells to treat cirrhosis . Our uncontrolled trial showed promising results for bone marrow mesenchymal stem cell ( MSC ) transplantation in cirrhosis . Therefore , we conducted a r and omized , placebo-controlled trial to evaluate the efficacy of autologous MSC transplantation in cirrhosis . METHODS The enrolled patients with decompensated cirrhosis were r and omly assigned to receive MSC or placebo infusions . A median of 195 million ( range : 120 - 295 million ) cultured MSCs were infused through a peripheral vein . The primary outcome was absolute changes in MELD score . Secondary outcomes were absolute changes in Child score , liver function tests and liver volumes between the MSC and placebo group 12 months after infusion . RESULTS A total of 27 patients were enrolled . Of these , 15 patients received MSC and 12 patients received placebo . One patient in the MSC group and one patient in the placebo group were lost to follow-up . Three patients in the MSC group died of liver failure 3 months ( one patient ) , or 5 months ( two patients ) after cellular infusion . The baseline MELD scores of the deceased patients were significantly higher than those who remained alive in either group ( 20.0 vs. 15.1 ; P = 0.02 ) . The absolute changes in Child scores , MELD scores , serum albumin , INR , serum transaminases and liver volumes did not differ significantly between the MSC and placebo groups at 12 months of follow-up . CONCLUSION Based on this r and omized controlled trial , autologous bone marrow MSC transplantation through peripheral vein probably has no beneficial effect in cirrhotic patients . Further studies with higher number of patients are warranted to better clarify the impact of MSC infusion through peripheral vein or portal vein in cirrhosis Decompensated liver cirrhosis ( LC ) , a life-threatening complication of chronic liver disease , is one of the major indications for liver transplantation . Recently , mesenchymal stem cell ( MSC ) transfusion has been shown to lead to the regression of liver fibrosis in mice and humans . This study examined the safety and efficacy of umbilical cord-derived MSC ( UC-MSC ) in patients with decompensated LC . A total of 45 chronic hepatitis B patients with decompensated LC , including 30 patients receiving UC-MSC transfusion , and 15 patients receiving saline as the control , were recruited ; clinical parameters were detected during a 1-year follow-up period . No significant side-effects and complications were observed in either group . There was a significant reduction in the volume of ascites in patients treated with UC-MSC transfusion compared with controls ( P < 0.05 ) . UC-MSC therapy also significantly improved liver function , as indicated by the increase of serum albumin levels , decrease in total serum bilirubin levels , and decrease in the sodium model for end-stage liver disease scores . UC-MSC transfusion is clinical ly safe and could improve liver function and reduce ascites in patients with decompensated LC . UC-MSC transfusion , therefore , might present a novel therapeutic approach for patients with decompensated LC BACKGROUND AND AIM Ursodeoxycholic acid ( UDCA ) treatment is an effective medical therapy for patients with primary biliary cirrhosis ( PBC ) ; however , 40 % of PBC patients show an incomplete response to the UDCA therapy . This study aim ed to investigate the safety and efficacy of umbilical cord-derived mesenchymal stem cell ( UC-MSC ) transfusion in PBC patients with an incomplete response to UDCA . METHODS We conducted a single-arm trial that included seven PBC patients with a suboptimal response to UDCA treatment . UC-MSCs were first cultured , and then 0.5 × 10(6 ) cells/kg body weights were infused through a peripheral vein . UC-MSCs were given three times at 4-week intervals , and patients were followed up for 48 weeks . Primary outcomes were to evaluate the safety and feasibility of UC-MSC treatment , and secondary outcomes were to evaluate liver functions and patient 's quality of life . RESULTS No obvious side-effects were found in the patients treated with UC-MSCs . Symptoms such as fatigue and pruritus were obviously alleviated in most patients after UC-MSC treatment . There was a significant decrease in serum alkaline phosphatase and γ-glutamyltransfer \n Output:\n " }, { "from": "agent", "value": "The majority of the analyzed studies showed improvements in liver function , ascites and encephalopathy .\nIn particular , an MA showed that MSC therapy improved the total bilirubin level , the serum albumin level and the Model for End-stage Liver Disease ( MELD ) score after MSC treatment .\nBased on these results , MSC transplantation is considered to be safe for the treatment of chronic liver disease ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: BACKGROUND Several studies have shown the efficacy , tolerability , and ease of administration of pemetrexed-an antifolate antineoplastic agent-in patients with advanced non-small-cell lung cancer . We assessed pemetrexed as maintenance therapy in patients with this disease . METHODS This r and omised double-blind study was undertaken in 83 centres in 20 countries . 663 patients with stage IIIB or IV disease who had not progressed on four cycles of platinum-based chemotherapy were r and omly assigned ( 2:1 ratio ) to receive pemetrexed ( 500 mg/m(2 ) , day 1 ) plus best supportive care ( n=441 ) or placebo plus best supportive care ( n=222 ) in 21-day cycles until disease progression . Treatment was r and omised with the Simon and Pocock minimisation method . Patients and investigators were masked to treatment . All patients received vitamin B(12 ) , folic acid , and dexamethasone . The primary endpoint of progression-free survival and the secondary endpoint of overall survival were analysed by intention to treat . This study is registered with Clinical Trials.gov , number NCT00102804 . FINDINGS All r and omly assigned participants were analysed . Pemetrexed significantly improved progression-free survival ( 4.3 months [ 95 % CI 4.1 - 4.7 ] vs 2.6 months [ 1.7 - 2.8 ] ; hazard ratio [ HR ] 0.50 , 95 % CI 0.42 - 0.61 , p<0.0001 ) and overall survival ( 13.4 months [ 11.9 - 15.9 ] vs 10.6 months [ 8.7 - 12.0 ] ; HR 0.79 , 0.65 - 0.95 , p=0.012 ) compared with placebo . Treatment discontinuations due to drug-related toxic effects were higher in the pemetrexed group than in the placebo group ( 21 [ 5 % ] vs three [ 1 % ] ) . Drug-related grade three or higher toxic effects were higher with pemetrexed than with placebo ( 70 [ 16 % ] vs nine [ 4 % ] ; p<0.0001 ) , specifically fatigue ( 22 [ 5 % ] vs one [ 1 % ] , p=0.001 ) and neutropenia ( 13 [ 3 % ] vs 0 , p=0.006 ) . No pemetrexed-related deaths occurred . Relatively fewer patients in the pemetrexed group than in the placebo group received systemic post-discontinuation therapy ( 227 [ 51 % ] vs 149 [ 67 % ] ; p=0.0001 ) . INTERPRETATION Maintenance therapy with pemetrexed is well tolerated and offers improved progression-free and overall survival compared with placebo in patients with advanced non-small-cell lung cancer . FUNDING Eli Lilly BACKGROUND We conducted a r and omized , placebo-controlled , double-blind trial to determine whether the epidermal growth factor receptor inhibitor erlotinib prolongs survival in non-small-cell lung cancer after the failure of first-line or second-line chemotherapy . METHODS Patients with stage IIIB or IV non-small-cell lung cancer , with performance status from 0 to 3 , were eligible if they had received one or two prior chemotherapy regimens . The patients were stratified according to center , performance status , response to prior chemotherapy , number of prior regimens , and prior platinum-based therapy and were r and omly assigned in a 2:1 ratio to receive oral erlotinib , at a dose of 150 mg daily , or placebo . RESULTS The median age of the 731 patients who underwent r and omization was 61.4 years ; 49 percent had received two prior chemotherapy regimens , and 93 percent had received platinum-based chemotherapy . The response rate was 8.9 percent in the erlotinib group and less than 1 percent in the placebo group ( P<0.001 ) ; the median duration of the response was 7.9 months and 3.7 months , respectively . Progression-free survival was 2.2 months and 1.8 months , respectively ( hazard ratio , 0.61 , adjusted for stratification categories ; P<0.001 ) . Overall survival was 6.7 months and 4.7 months , respectively ( hazard ratio , 0.70 ; P<0.001 ) , in favor of erlotinib . Five percent of patients discontinued erlotinib because of toxic effects . CONCLUSIONS Erlotinib can prolong survival in patients with non-small-cell lung cancer after first-line or second-line chemotherapy Background Overexpression of RRM1 and RRM2 has been associated with gemcitabine resistance . BRCA1 overexpression increases sensitivity to paclitaxel and docetaxel . We have retrospectively examined the effect of RRM1 , RRM2 and BRCA1 expression on outcome to gemcitabine plus docetaxel in advanced non-small-cell lung cancer ( NSCLC ) patients . Methodology and Principal Findings Tumor sample s were collected from 102 chemotherapy-naïve advanced NSCLC patients treated with gemcitabine plus docetaxel as part of a r and omized trial . RRM1 , RRM2 and BRCA1 mRNA levels were assessed by quantitative PCR and correlated with response , time to progression and survival . As BRCA1 levels increased , the probability of response increased ( Odds Ratio [ OR ] , 1.09 : p = 0.01 ) and the risk of progression decreased ( hazard ratio [ HR ] , 0.99 ; p = 0.36 ) . As RRM1 and RRM2 levels increased , the probability of response decreased ( RRM1 : OR , 0.97 ; p = 0.82 ; RRM2 : OR , 0.94 ; p<0.0001 ) and the risk of progression increased ( RRM1 : HR , 1.02 ; p = 0.001 ; RRM2 : HR , 1.005 ; p = 0.01 ) . An interaction observed between BRCA1 and RRM1 allowed patients to be classified in three risk groups according to combinations of gene expression levels , with times to progression of 10.13 , 4.17 and 2.30 months ( p = 0.001 ) . Low BRCA1 expression was the only factor significantly associated with longer time to progression in 31 patients receiving cisplatin-based second-line therapy . Conclusions The mRNA expression of BRCA1 , RRM1 and RRM2 is potentially a useful tool for selecting NSCLC patients for individualized chemotherapy and warrants further investigation in prospect i ve studies Purpose : No chemotherapy regimen , including the widely used combination of gemcitabine/cisplatin , confers significantly improved survival over any other in metastatic non-small cell lung cancer ( NSCLC ) ; however , the selection of patients according to key genetic characteristics can help to tailor chemotherapy . Ribonucleotide reductase subunit M1 ( RRM1 ) is involved in DNA synthesis and repair and in gemcitabine metabolism , and the excision repair cross-complementing group 1 ( ERCC1 ) gene has been related to cisplatin activity . Experimental Design : Patients were part of a large r and omized trial carried out from September 1998 to July 2000 , comparing gemcitabine/cisplatin versus gemcitabine/cisplatin/vinorelbine versus gemcitabine/vinorelbine followed by vinorelbine/ifosfamide . We analyzed RRM1 and ERCC1 mRNA expression in paraffin-embedded sample s obtained from bronchoscopy by real-time quantitative reverse transcription-PCR . Results were correlated with survival using the Kaplan-Meier method . Results : A total of 100 patients were assessed . There was a strong correlation between RRM1 and ERCC1 mRNA expression levels ( Spearman r = 0.410 ; P < 0.001 ) . In the gemcitabine/cisplatin arm , patients with low RRM1 mRNA expression levels had significantly longer median survival than those with high levels [ 13.7 versus 3.6 months ; 95 % confidence interval ( CI ) , 9.6–17.8 months ; P = 0.009 ] . Median survival was also significantly longer among patients with low mRNA expression levels of both RRM1 and ERCC1 ( not reached ) , than among those with high levels of both genes ( 6.8 months ; 95 % CI , 2.6–11.1 months ; P = 0.016 ) . Conclusions : RRM1 mRNA expression is a crucial predictive marker of survival in gemcitabine/cisplatin-treated patients . Genetic testing of RRM1 mRNA expression levels can and should be used to personalize chemotherapy PURPOSE V and etanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor ( VEGFR ) and epidermal growth factor receptor ( EGFR ) signaling . In this two-part phase II study , the efficacy and safety of v and etanib was compared with that of gefitinib , an inhibitor of EGFR signaling . PATIENTS AND METHODS Patients ( N = 168 ) with locally advanced or metastatic ( stage IIIB/IV ) non-small-cell lung cancer ( NSCLC ) , after failure of first-line with or without second-line platinum-based chemotherapy , received once-daily v and etanib 300 mg ( n = 83 ) or gefitinib 250 mg ( n = 85 ) until disease progression or evidence of toxicity ( part A ) . After a 4-week washout period , eligible patients had the option to switch to the alternative treatment ( part B ) . Progression-free survival ( PFS ) was the primary efficacy assessment in part A , which was design ed to have a higher than 75 % power to detect a 33 % prolongation of PFS at a one-sided significance level of .2 . RESULTS In part A , v and etanib prolonged PFS compared with gefitinib ( hazard ratio = 0.69 ; 95 % CI , 0.50 to 0.96 ; one-sided P = .013 ) . Patients receiving v and etanib experienced adverse events that were manageable and generally consistent with inhibition of EGFR and VEGFR signaling , including diarrhea , rash , and hypertension . There were no unexpected safety findings with gefitinib . Overall survival , a secondary assessment , was not significantly different between patients initially r and omly assigned to either v and etanib or gefitinib . CONCLUSION The primary efficacy objective was achieved , with v and etanib demonstrating a significant prolongation of PFS versus gefitinib . V and etanib 300 mg/d is currently being evaluated as a monotherapy in two r and omized phase III studies in advanced NSCLC PURPOSE To confirm the promising phase II results of docetaxel monotherapy , this phase III trial was conducted of chemotherapy for patients with advanced non-small-cell lung cancer ( NSCLC ) who had previously failed platinum-containing chemotherapy . PATIENTS AND METHODS A total of 373 patients were r and omized to receive either docetaxel 100 mg/m(2 ) ( D100 ) or 75 mg/m(2 ) ( D75 ) versus a control regimen of vinorelbine or ifosfamide ( V/I ) . The three treatment groups were well-balanced for key patient characteristics . RESULTS Overall response rates were 10.8 % with D100 and 6.7 % with D75 , each significantly higher than the 0.8 % response with V/I ( P = .001 and P = .036 , respectively ) . Patients who received docetaxel had a longer time to progression ( P = .046 , by log-rank test ) and a greater progression-free survival at 26 weeks ( P = .005 , by chi(2 ) test ) . Although overall survival was not significantly different between the three groups , the 1-year survival was significantly greater with D75 than with the control treatment ( 32 % v 19 % ; P = .025 , by chi(2 ) test ) . Prior exposure to paclitaxel did not decrease the likelihood of response to docetaxel , nor did it impact survival . There was a trend toward greater efficacy in patients whose disease was platinum-resistant rather than platinum-refractory and in patients with performance status of 0 or 1 versus 2 . Toxicity was greatest with D100 , but the D75 arm was well-tolerated . CONCLUSION This first r and omized trial in this setting demonstrates that D75 every 3 weeks can offer clinical ly meaningful benefit to patients with advanced NSCLC whose disease has relapsed or progressed after platinum-based chemotherapy PURPOSE To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non-small-cell lung cancer who had previously been treated with platinum-based chemotherapy . Secondary end points included assessment of response ( docetaxel arm only ) , toxicity , and quality of life . PATIENTS AND METHODS Patients with performance statuses of 0 to 2 and stage IIIB/IV non-small-cell lung cancer with either measurable or evaluable lesions were eligible for entry onto the study if they had undergone one or more platinum-based chemotherapy regimens and if they had adequate hematology and \n Output:\n " }, { "from": "agent", "value": "There is some evidence that histology is prognostic for survival .\nThere is evidence from multiple r and omized clinical trials to recommend the following : histologic subtype is predictive of treatment efficacy and for some agents toxicity .\nClinical data on K-RAS mutations are inconsistent , therefore testing is not recommended .\nThere is insufficient evidence to recommend other biomarker testing .\nNo biomarkers to date reliably predict improved efficacy for anti-VEGF therapy ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: The purpose of this study was to determine the effects of beta-alanine supplementation and high-intensity interval training ( HIIT ) on electromyographic fatigue threshold ( EMGFT ) and efficiency of electrical activity ( EEA ) . A total of 46 men completed four , 2-min work bouts on a cycle ergometer . Using bipolar surface electrodes , the EMG amplitude was averaged and plotted over the 2-min . The result ing slopes were used to calculate EMGFT and EEA . Following initial testing , all participants were r and omly assigned to either placebo ( PL ; n = 18 ) , beta-alanine ( BA ; n = 18 ) or control groups ( CON ; n = 10 ) . Following r and omization , participants engaged in 6 weeks of HIIT training . Significant improvements in EMGFT and EEA result ed for both training groups . In conclusion , HIIT appeared to be the primary stimulus effecting EMGFT or EEA , suggesting adaptations from HIIT may be more influential than increasing skeletal muscle carnosine levels on delaying fatigue in recreationally active men Summary .The effect of beta-alanine ( β-Ala ) alone or in combination with creatine monohydrate ( Cr ) on aerobic exercise performance is unknown . The purpose of this study was to examine the effects of 4 weeks of β-Ala and Cr supplementation on indices of endurance performance . Fifty-five men ( 24.5 ± 5.3 yrs ) participated in a double-blind , placebo-controlled study and r and omly assigned to one of 4 groups ; placebo ( PL , n = 13 ) , creatine ( Cr , n = 12 ) , beta-alanine ( β-Ala , n = 14 ) , or beta-alanine plus creatine ( CrBA , n = 16 ) . Prior to and following supplementation , participants performed a grade d exercise test on a cycle ergometer to determine VO2peak , time to exhaustion ( TTE ) , and power output , VO2 , and percent VO2peak associated with VT and LT . No significant group effects were found . However , within groups , a significant time effect was observed for CrBa on 5 of the 8 parameters measured . These data suggest that CrBA may potentially enhance endurance performance The aim of this study was to examine the effect of β-alanine supplementation on repeated sprint performance during an intermittent exercise protocol design ed to replicate games play . Sixteen elite and twenty non-elite game players performed the Loughborough Intermittent Shuttle Test ( LIST ) on two separate occasions . Trials were separated by 4 weeks of supplementation with either β-alanine ( BA ) or maltodextrin ( MD ) . There was no deterioration in sprint times from Set 1 to Set 6 of the LIST in either group prior to supplementation ( elite : P = 0.92 ; non-elite : P = 0.12 ) . Neither BA nor MD supplementation affected sprint times . Blood lactate concentrations were elevated during exercise in both groups , with no effect of supplementation . β-Alanine supplementation did not significantly improve sprint performance during the LIST . Neither group showed a performance decrement prior to supplementation , which might have masked any benefit from increased muscle buffering capacity due to β-alanine supplementation Beta-alanine may benefit short- duration , high-intensity exercise performance . The aim of this r and omized double-blind placebo-controlled study was to examine the effects of beta-alanine supplementation on aspects of muscular performance in highly trained cyclists . Sixteen highly trained cyclists ( mean ± SD ; age = 24 ± 7 yr ; mass = 70 ± 7 kg ; VO2max = 67 ± 4 ml · kg(-1 ) · min(-1 ) ) supplemented with either beta-alanine ( n = 8 , 65 mg · kg - 1BM ) or a placebo ( n = 8 ; dextrose monohydrate ) over 4 weeks . Pre- and postsupplementation cyclists performed a 4-minute maximal cycling test to measure average power and 30 reciprocal maximal isokinetic knee contractions at a fixed angular velocity of 180 ° · sec(-1 ) to measure average power/repetition , total work done ( TWD ) , and fatigue index ( % ) . Blood pH , lactate ( La- ) and bicarbonate ( HCO3- ) concentrations were measured pre- and postisokinetic testing at baseline and following the supplementation period . Beta-alanine supplementation was 44 % likely to increase average power output during the 4-minute cycling time trial when compared with the placebo , although this was not statistically significant ( p = .25 ) . Isokinetic average power/repetition was significantly increased post beta-alanine supplementation compared with placebo ( beta-alanine : 6.8 ± 9.9 W , placebo : -4.3 ± 9.5 W , p = .04 , 85 % likely benefit ) , while fatigue index was significantly reduced ( p = .03 , 95 % likely benefit ) . TWD was 89 % likely to be improved following beta-alanine supplementation ; however , this was not statistically significant ( p = .09 ) . There were no significant differences in blood pH , lactate , and HCO3- between groups ( p > .05 ) . Four weeks of beta-alanine supplementation result ed in worthwhile changes in time-trial performance and short- duration muscular force production in highly trained cyclists Background Ageing is associated with a significant reduction in skeletal muscle carnosine which has been linked with a reduction in the buffering capacity of muscle and in theory , may increase the rate of fatigue during exercise . Supplementing beta-alanine has been shown to significantly increase skeletal muscle carnosine . The purpose of this study , therefore , was to examine the effects of ninety days of beta-alanine supplementation on the physical working capacity at the fatigue threshold ( PWCFT ) in elderly men and women . Methods Using a double-blind placebo controlled design , twenty-six men ( n = 9 ) and women ( n = 17 ) ( age ± SD = 72.8 ± 11.1 yrs ) were r and omly assigned to either beta-alanine ( BA : 800 mg × 3 per day ; n = 12 ; CarnoSyn ™ ) or Placebo ( PL ; n = 14 ) group . Before ( pre ) and after ( post ) the supplementation period , participants performed a discontinuous cycle ergometry test to determine the PWCFT . Results Significant increases in PWCFT ( 28.6 % ) from pre- to post-supplementation were found for the BA treatment group ( p < 0.05 ) , but no change was observed with PL treatment . These findings suggest that ninety days of BA supplementation may increase physical working capacity by delaying the onset of neuromuscular fatigue in elderly men and women . Conclusion We suggest that BA supplementation , by improving intracellular pH control , improves muscle endurance in the elderly . This , we believe , could have importance in the prevention of falls , and the maintenance of health and independent living in elderly men and women Abstract Smith-Ryan , AE , Fukuda , DH , Stout , JR , and Kendall , KL . High-velocity intermittent running : effects of beta-alanine supplementation . J Strength Cond Res 26(10 ) : 2798–2805 , 2012—The use of & bgr;-alanine in sport is widespread . However , the effects across all sport activities are inconclusive . The purpose of this study was to evaluate the effects of & bgr;-alanine supplementation on high-intensity running performance and critical velocity ( CV ) and anaerobic running capacity ( ARC ) . Fifty recreationally trained men were r and omly assigned , in a double-blind fashion , to a & bgr;-alanine group ( BA , 2 × 800 mg tablets , 3 times daily ; CarnoSyn ; n = 26 ) or placebo group ( PL , 2 × 800 mg maltodextrin tablets , 3 times daily ; n = 24 ) . A grade d exercise test ( GXT ) was performed to establish peak velocity ( PV ) . Three high-speed runs to exhaustion were performed at 110 , 100 , and 90 % of PV , with 15 minutes of rest between bouts . The distances achieved were plotted over the time to exhaustion ( TTE ) . Linear regression was used to determine the slope ( CV ) and y-intercept ( ARC ) of these relationships to assess aerobic and anaerobic performances , respectively . There were no significant treatment effects ( p > 0.05 ) on CV or ARC for either men or women . Additionally , no TTE effects were evident for bouts at 90–110%PV lasting 1.95–5.06 minutes . There seems to be no ergogenic effect of & bgr;-alanine supplementation on CV , ARC , or high-intensity running lasting approximately 2–5 minutes in either men or women in the current study Carnosine ( β-alanyl-l-histidine ) is found in high concentrations in skeletal muscle and chronic β-alanine ( BA ) supplementation can increase carnosine content . This placebo-controlled , double-blind study compared two different 8-week BA dosing regimens on the time course of muscle carnosine loading and 8-week washout , leading to a BA dose – response study with serial muscle carnosine assessment s throughout . Thirty-one young males were r and omized into three BA dosing groups : ( 1 ) high – low : 3.2 g BA/day for 4 weeks , followed by 1.6 g BA/day for 4 weeks ; ( 2 ) low – low : 1.6 g BA/day for 8 weeks ; and ( 3 ) placebo . Muscle carnosine in tibialis-anterior ( TA ) and gastrocnemius ( GA ) muscles was measured by 1H-MRS at weeks 0 , 2 , 4 , 8 , 12 and 16 . Flushing symptoms and blood clinical chemistry were trivial in all three groups and there were no muscle carnosine changes in the placebo group . During the first 4 weeks , the increase for high – low ( TA 2.04 mmol/kgww , GA 1.75 mmol/kgww ) was ~twofold greater than low – low ( TA 1.12 mmol/kgww , GA 0.80 mmol/kgww ) . 1.6 g BA/day significantly increased muscle carnosine within 2 weeks and induced continual rises in already augmented muscle carnosine stores ( week 4–8 , high – low regime ) . The dose – response showed a carnosine increase of 2.01 mmol/kgww per 100 g of consumed BA , which was only dependent upon the total accumulated BA consumed ( within a daily intake range of 1.6–3.2 g BA/day ) . Washout rates were gradual ( 0.18 mmol/kgww and 0.43 mmol/kgww/week ; ~2%/week ) . In summary , the absolute increase in muscle carnosine is only dependent upon the total BA consumed and is not dependent upon baseline muscle carnosine , the muscle type , or the daily amount of supplemented BA Background β-Alanine ( βA ) has been shown to improve performance during cycling . This study was the first to examine the effects of βA supplementation on the onset of blood lactate accumulation ( OBLA ) during incremental treadmill running . Methods Seventeen recreationally-active men ( mean ± SE 24.9 ± 4.7 yrs , 180.6 ± 8.9 cm , 79.25 ± 9.0 kg ) participated in this r and omized , double-blind , placebo-controlled pre/post test 2-treatment experimental design . Subjects participated in two incremental treadmill tests before and after 28 days of supplementation with either βA ( 6.0 g·d-1)(βA , n = 8) or an equivalent dose of Maltodextrin as the Placebo ( PL , n = 9 ) . Heart rate , percent heart rate maximum ( % HRmax ) , % VO2max@OBLA ( 4.0 mmol . L-1 blood lactate concentration ) and VO2max ( L.min-1 ) were determined for each treadmill test . Friedman test was used to determine within group differences ; and Mann-Whitney was used to determine between group differences for pre and post values ( p < 0.05 ) . Results The βA group experienced a significant rightward shift in HR@OBLA beats.min-1 ( p < 0.01 ) pre/post ( 161.6 ± 19.2 to 173.6 ± 9.9 ) but remained unchanged in the PL group ( 166.8 ± 15.8 to 169.6 ± 16.1 ) . The % HRmax@OBLA increased ( p < 0.05 ) pre/post in the βA group ( 83.0 % ± 9.7 to 88.6 % ± 3.7 ) versus no change in the PL group ( 86.3 ± % 4.8 to 87.9 % ± 7.2 ) . The % VO2max@OBLA increased ( p < 0.05 ) in the βA group pre/post ( 69.1 ± 11.0 to 75.6 ± 10.7 ) but remained unchanged in the PL group ( 73.3 ± 7.3 to 74.3 ± 7.3 ) . VO2max ( L.min-1 ) decreased ( p < 0.01 ) in the βA group pre \n Output:\n " }, { "from": "agent", "value": "Summary / conclusions & bgr;-alanine had a significant overall effect while subgroup analyses revealed a number of modifying factors .\nThese data allow individuals to make informed decisions as to the likelihood of an ergogenic effect with & bgr;-alanine supplementation based on their chosen exercise modality" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: The purpose of this study was to describe the life-sustaining treatment preferences of dialysis patients and to compare the acceptability of two generic and a disease-specific advance directive ( AD ) . Of 532 potentially eligible hemodialysis patients , 95 ( 17.9 % ) participated in the study . These patients completed two generic ( the Centre for Bioethics Living Will and the Medical Directive ) and one disease-specific ( the Dialysis Living Will ) AD in a r and omized cross-over trial . Treatment preferences were measured by using the Centre for Bioethics Living Will . Acceptability of the AD was measured by using a 13-item advance directive acceptability question naire ( ADAQ ) for each AD , and the advance directive choice question naire ( ADCQ ) to elicit participants ' preferred AD . Twenty-five percent of the participants wanted to continue dialysis in case of severe stroke , 19 % in severe dementia , and 14 % in permanent coma . Averaged across treatments , proportions of participants wanting treatment in various health states were : current health ( 86 % ) , mild stroke ( 84 % ) , moderate stroke ( 60 % ) , severe stroke ( 21 % ) , mild dementia ( 78 % ) , moderate dementia ( 51 % ) , severe dementia ( 14 % ) , terminal illness ( 41 % ) , and permanent coma ( 10 % ) . Averaged across health states , proportions of participants wanting various types of treatment were : dialysis ( 58 % ) , antibiotics ( 53 % ) , transfusion ( 53 % ) , surgery ( 48 % ) , cardiopulmonary resuscitation ( 48 % ) , respirator ( 47 % ) , and tube feeding ( 41 % ) . Mean ADAQ scores were : Dialysis Living Will , 71 % ; Centre for Bioethics Living Will , 70 % ; and Medical Directive , 60 % ( F = 8.27 , P < 0.001 ( repeat measures analysis of variance ) ; the Dialysis Living Will and Centre for Bioethics Living Will scored significantly higher than the Medical Directive ) . The proportion of participants who said they would choose to complete each AD was : Dialysis Living Will , 28 % ; Centre for Bioethics Living Will , 38 % ; Medical Directive , 31 % ; and unsure , 3 % ( chi 2 = 1.465 , df = 2 , P = 0.48 ) . In conclusion , twenty-five percent or less of hemodialysis patients want to continue dialysis in three specific health states : severe stroke , severe dementia , and permanent coma . Health states and illness severity , far more than treatment descriptions , influence preferences . Dialysis patients should be offered a generic AD , and some generic AD are more acceptable than others . Only a minority of dialysis patients will complete any AD , but the completion of written AD forms is only one element in the process of advance care planning BACKGROUND African Americans ' beliefs about end-of-life care may differ from those of whites , but racial differences in advance care planning ( ACP ) outcomes are unknown . OBJECTIVE The aim of this study was to compare the efficacy of an ACP intervention on preparation for end-of-life decision making and post-bereavement outcomes for African Americans and whites on dialysis . METHOD A secondary analysis of data from a r and omized trial comparing an ACP intervention ( Sharing Patient 's Illness Representations to Increase Trust [ SPIRIT ] ) with usual care was conducted . There were 420 participants , 210 patient-surrogate dyads ( 67.4 % African Americans ) , recruited from 20 dialysis centers in North Carolina . The outcomes of preparation for end-of-life decision making included dyad congruence on goals of care , surrogate decision-making confidence , a composite of the two , and patient decisional conflict assessed at 2 , 6 , and 12 months post-intervention . Surrogate bereavement outcomes included anxiety , depression , and post-traumatic distress symptoms assessed at 2 weeks , and at 3 and 6 months after the patient 's death . RESULTS SPIRIT was superior to usual care in improving dyad congruence ( odds ration [ OR ] = 2.31 , p = 0.018 ) , surrogate decision-making confidence ( β = 0.18 , p = 0.021 ) , and the composite ( OR = 2.19 , p = 0.028 ) 2 months post-intervention , but only for African Americans . SPIRIT reduced patient decisional conflict at 6 months for whites and at 12 months for African Americans . Finally , SPIRIT was superior to usual care in reducing surrogates ' bereavement depressive symptoms for African Americans but not for whites ( β = -3.49 , p = 0.003 ) . CONCLUSION SPIRIT was effective in improving preparation for end-of-life decision-making and post-bereavement outcomes in African Americans Background We studied the distribution of causes of death in the CONTRAST cohort and compared the proportion of cardiovascular deaths with other population s to answer the question whether cardiovascular mortality is still the principal cause of death in end stage renal disease . In addition , we compared patients who died from the three most common death causes . Finally , we aim ed to study factors related to dialysis withdrawal . Methods We used data from CONTRAST , a r and omized controlled trial in 714 chronic hemodialysis patients comparing the effects of online hemodiafiltration versus low-flux hemodialysis . Causes of death were adjudicated . The distribution of causes of death was compared to that of the Dutch dialysis registry and of the Dutch general population . Results In CONTRAST , 231 patients died on treatment . 32 % died from cardiovascular disease , 22 % due to infection and 23 % because of dialysis withdrawal . These proportions were similar to those in the Dutch dialysis registry and the proportional cardiovascular mortality was similar to that of the Dutch general population . cardiovascular death was more common in patients < 60 years . Patients who withdrew were older , had more co-morbidity and a lower mental quality of life at baseline . Patients who withdrew had much co-morbidity . 46 % died within 5 days after the last dialysis session . Conclusions Although the absolute risk of death is much higher , the proportion of cardiovascular deaths in a prevalent end stage renal disease population is similar to that of the general population . In older hemodialysis patients cardiovascular and non-cardiovascular death risk are equally important . Particularly the registration of dialysis withdrawal deserves attention . These findings may be partly limited to the Dutch population The prevalence of and mortality from chronic kidney disease ( CKD ) are high among African Americans . Interventions to improve knowledge of the likely illness course and the benefits and risks of life-sustaining treatment at the end-of-life are needed for African Americans with CKD and their surrogate decision makers . Nineteen African Americans with stage 5 CKD and their surrogates were r and omized to either patient-centered advance care planning ( PC-ACP ) or usual care . PC-ACP dyads showed greater improvement in congruence in end-of-life treatment preferences ( p < .05 ) and higher perceived quality of communication ( p < .05 ) than do control dyads , but the two groups did not differ on other primary outcomes or acceptability measures , such as perceptions of cultural appropriateness . At posttest , 80 % of patients in the intervention group reported that they would choose to continue all life-sustaining treatments in a situation of a low chance of survival , whereas 28.6 % of patients in the control group reported that they would make that choice . At posttest , 90 % of patients in the intervention group reported that they would choose to undergo cardiopulmonary resuscitation even if the chance of surviving the attempt would be low , whereas 57 % of patients in the control group reported that they would make that choice . PC-ACP can be effective in improving patient and surrogate congruence in end-of-life treatment preferences . However , the results suggest a need for further improvements in the intervention to enhance cultural appropriateness for African Americans with CKD CONTEXT Talking about death can be difficult . Without evidence that end-of-life discussion s improve patient outcomes , physicians must balance their desire to honor patient autonomy against a concern of inflicting psychological harm . OBJECTIVE To determine whether end-of-life discussion s with physicians are associated with fewer aggressive interventions . DESIGN , SETTING , AND PARTICIPANTS A US multisite , prospect i ve , longitudinal cohort study of patients with advanced cancer and their informal caregivers ( n = 332 dyads ) , September 2002-February 2008 . Patients were followed up from enrollment to death , a median of 4.4 months later . Bereaved caregivers ' psychiatric illness and quality of life was assessed a median of 6.5 months later . MAIN OUTCOME MEASURES Aggressive medical care ( eg , ventilation , resuscitation ) and hospice in the final week of life . Secondary outcomes included patients ' mental health and caregivers ' bereavement adjustment . RESULTS One hundred twenty-three of 332 ( 37.0 % ) patients reported having end-of-life discussion s before baseline . Such discussion s were not associated with higher rates of major depressive disorder ( 8.3 % vs 5.8 % ; adjusted odds ratio [ OR ] , 1.33 ; 95 % confidence interval [ CI ] , 0.54 - 3.32 ) , or more worry ( mean McGill score , 6.5 vs 7.0 ; P = .19 ) . After propensity-score weighted adjustment , end-of-life discussion s were associated with lower rates of ventilation ( 1.6 % vs 11.0 % ; adjusted OR , 0.26 ; 95 % CI , 0.08 - 0.83 ) , resuscitation ( 0.8 % vs 6.7 % ; adjusted OR , 0.16 ; 95 % CI , 0.03 - 0.80 ) , ICU admission ( 4.1 % vs 12.4 % ; adjusted OR , 0.35 ; 95 % CI , 0.14 - 0.90 ) , and earlier hospice enrollment ( 65.6 % vs 44.5 % ; adjusted OR , 1.65;95 % CI , 1.04 - 2.63 ) . In adjusted analyses , more aggressive medical care was associated with worse patient quality of life ( 6.4 vs 4.6 ; F = 3.61 , P = .01 ) and higher risk of major depressive disorder in bereaved caregivers ( adjusted OR , 3.37 ; 95 % CI , 1.12 - 10.13 ) , whereas longer hospice stays were associated with better patient quality of life ( mean score , 5.6 vs 6.9 ; F = 3.70 , P = .01 ) . Better patient quality of life was associated with better caregiver quality of life at follow-up ( beta = .20 ; P = .001 ) . CONCLUSIONS End-of-life discussion s are associated with less aggressive medical care near death and earlier hospice referrals . Aggressive care is associated with worse patient quality of life and worse bereavement adjustment The population -based dialysis rate in Ontario more than doubled between 1981 and 1992 ; yet there is concern about over-loaded facilities , delayed treatment and denial of dialysis through nonreferral and implicit rationing . A working party involving several stakeholders has been established in Ontario to address these issues . However , clinical policy making concerning dialysis services is impeded in all provinces by a lack of information . The causes of the moderately large variations in dialysis rates from province to province remain unclear . The exact extent and risks of delayed therapy have not been well defined . Dialysis protocol s vary inexplicably among centres , and cost data on different methods of providing dialysis are limited . Many steps could be taken in Ontario and other provinces to generate a better information base for planning and managing dialysis services . Predialysis clinics with outreach programs could help to ensure equitable access to this life-saving therapy . Criteria for choosing modes and intensities of renal-replacement therapy must be review ed . In areas of clear disagreement and uncertainty , patients could be r and omly assigned to different protocol s and outcomes studied . In areas of agreement , the criteria should be st and ardized . Advance directives may help ascertain patients ' wishes concerning the initiation or continuation of dialysis , and more accurate data on prognosis of different patient subgroups would aid in early identification of patients in a hopelessly deteriorating situation . Last , studies comparing the \" output \" ( e.g. , hours on hemodialysis ) per dollar of different dialysis units and modalities are also needed to ensure that all facilities are opening efficiently without compromising patient outcomes BACKGROUND Recent studies suggest that surrogate decision makers may be too optimistic about their end-of-life decision making abilities for loved ones . We examined surrogates ' decision making confidence with an emphasis on its linkages to their underst and ings of patients ' values and goals for end-of-life care . METHODS We used baseline data from a r and omized trial with 58 dyads of African-American dialysis patients and their surrogates who separately completed the Values of Life-Sustaining Treatment Outcomes and the Goals of Care documents . Surrogates also completed a Surrogate Decision Making Confidence Scale . RESULTS Overall , 60 % of surrogates were unsure how their loved ones would feel about continuing life-sustaining treatment , including dialysis , in at least one of the four outcomes presented in the Values of Life-Sustaining Treatment Outcomes . For goals of care near end of life , 67.2 % to 69.0 % of patients preferred comfort care only , but only 20 ( 34.5 \n Output:\n " }, { "from": "agent", "value": "We found sparse data that were assessed at suboptimal quality and therefore we were unable to formulate conclusions about whether advance care planning can influence numbers of hospital admissions and treatment required by people with ESKD , or if patients ' advance care directives were followed at end-of-life ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: A total of 132 infants and children with grade s III and IV primary vesicoureteral reflux was entered into a prospect i ve trial comparing medical to surgical management . Inclusion criteria were an age not exceeding 10 years and a glomerular filtration rate of at least 70 ml . per minute per 1.73 m.2 . Children with significant urinary tract malformations and clinical signs/symptoms of dysfunctional voiding were not accepted into the trial . Medical therapy consisted of continuous low dose antibiotic prophylaxis until vesicoureteral reflux resolved . The type of surgical procedure used for the correction of reflux was left to the discretion of the surgeon . Outcome variables included the appearance or progression of renal lesions , rate of renal growth , recurrence rate of urinary tract infection or pyelonephritis , changes in total kidney glomerular filtration rate , development of hypertension and resolution rate of vesicoureteral reflux . Followup at 6 , 18 , 36 and 54 months after entry included , in addition to history and physical examination , voiding cystourethrography , excretory urography and a urine culture . Of the patients 68 were allocated to the medical group and 64 to the surgical group . They were stratified for age , sex and preexisting renal scarring . Of the patients 10 % were boys , 47 % were between 2 and 6 years old at entry , 93 % had a history of pyelonephritis , 67 % had either scarring or thinning of the parenchyma at entry , 87 % had grade IV vesicoureteral reflux in at least 1 unit and 56 % had bilateral reflux . There were no significant differences in the frequency distribution of entry characteristics between the patients allocated to either group . New renal scarring developed in 22 % of medical and 31 % of surgical patients ( p < 0.4 ) . Growth of kidneys with grade IV vesicoureteral reflux was slightly less than normal in the medical ( -0.67 + /- 0.15 st and ard deviation ) and surgical ( -0.42 + /- 0.11 st and ard deviation ) groups ( p < 0.7 ) . Pyelonephritis occurred in 15 medical patients versus 5 surgical patients ( p < 0.05 ) . There was no significant change in glomerular filtration rate within each treatment group and no difference in glomerular filtration rate between groups . No patient had hypertension during the followup period . The disappearance rate of vesicoureteral reflux in patients with grade IV reflux was approximately 8 % per year . Of the medical patients 75 % still had vesicoureteral reflux after 3 years of observation . ( ABSTRACT TRUNCATED AT 400 WORDS Background Several recent review s have evaluated evidence on the efficacy of Mindfulness-Based Stress Reduction ( MBSR ) among fibromyalgia sufferers , and concluded that more research should test effects on both psychological and physiological functioning . Purpose We conducted a r and omized prospect i ve trial of MBSR among female fibromyalgia patients . Methods Effects on perceived stress , pain , sleep quality , fatigue , symptom severity , and salivary cortisol were tested in treatment ( n = 51 ) versus wait-list control participants ( n = 40 ) using data at baseline , post-program , and 2-month follow-up . Results Analyses revealed that MBSR significantly reduced perceived stress , sleep disturbance , and symptom severity , with gains maintained at follow-up . Greater home practice at follow-up was associated with reduced symptom severity . MBSR did not significantly alter pain , physical functioning , or cortisol profiles . Conclusion MBSR ameliorated some of the major symptoms of fibromyalgia and reduced subjective illness burden . Further exploration of MBSR effects on physiological stress responses is warranted . These results support use of MBSR as a complementary treatment for women with fibromyalgia ( IS RCT N : 34628811 ) Abstract Introduction Fibromyalgia ( FM ) is characterized by chronic pain . Impaired growth hormone responses and reduced serum insulin-like growth factor 1 ( IGF-1 ) are common in FM . The aim was to examine changes in serum IGF-1 , cerebrospinal fluid ( CSF ) , neuropeptides , and cytokines during aerobic exercise in FM patients . Methods In total , 49 patients ( median age , 52 years ) with FM were included in the study . They were r and omized to either the moderate- to high-intensity Nordic Walking ( NW ) program ( n = 26 ) or the supervised low-intensity walking ( LIW ) program ( n = 23 ) . Patients participated in blood tests before and after 15 weeks of aerobic exercise . Changes in serum levels of free IGF-1 , pain rating on a 0- to 100-mm scale , pain threshold , and 6-minute walk test ( 6MWT ) were examined . CSF , neuropeptides , matrix metalloproteinase 3 ( MMP-3 ) , and inflammatory cytokines were determined . Nonparametric tests were used for group comparisons and correlation analyses . Results Serum free IGF-1 levels did not change during 15 weeks of exercise between the two groups , although the 6MWT significantly improved in the NW group ( p = 0.033 ) when compared with LIW . Pain did not significantly change in any of the groups , but tended to decrease ( p = 0.052 ) over time in the total group . A tendency toward a correlation was noted between baseline IGF-1 and a decrease of pain in response to exercise ( r = 0.278 ; p = 0.059 ) . When adjusted for age , this tendency disappeared . The change in serum free IGF-1 correlated positively with an alteration in CSF substance P ( SP ) levels ( rs= 0.495 ; p = 0.072 ) , neuropeptide Y ( NPY ) ( rs = 0.802 ; p = 0.001 ) , and pain threshold ( rs = 0.276 ; p = 0.058 ) . Differing CSF SP levels correlated positively to a change in pain threshold ( rs= 0.600 ; p = 0.023 ) , whereas the shift in CSF MMP-3 inversely correlated with an altered pain threshold ( rs= -0.569 ; p = 0.034 ) . Conclusions The baseline level of serum free IGF-1 did not change during high or low intensity of aerobic exercise . Changes in IGF-1 correlated positively with a variation in CSF SP , NPY , and pain threshold . These data indicate a beneficial role of IGF-1 during exercise in FM.Trial registration : Clinical Trials.gov NCT00643006 OBJECTIVE To determine the prevalence and characteristics of fibromyalgia in the general population . METHODS A r and om sample of 3,006 persons in Wichita , KS , were characterized according to the presence of no pain , non-widespread pain , and widespread pain . A sub sample of 391 persons , including 193 with widespread pain , were examined and interviewed in detail . RESULTS The prevalence of fibromyalgia was 2.0 % ( 95 % confidence interval [ 95 % CI ] 1.4 , 2.7 ) for both sexes , 3.4 % ( 95 % CI 2.3 , 4.6 ) for women , and 0.5 % ( 95 % CI 0.0 , 1.0 ) for men . The prevalence of the syndrome increased with age , with highest values attained between 60 and 79 years ( > 7.0 % in women ) . Demographic , psychological , dolorimetry , and symptom factors were associated with fibromyalgia . CONCLUSION Fibromyalgia is common in the population , and occurs often in older persons . Characteristic features of fibromyalgia -- pain threshold and symptoms -- are similar in community and clinic population s , but overall severity , pain , and functional disability are more severe in the clinic population Objective In this prospect i ve longitudinal clinical study , we evaluated the role of proinflammatory cytokine IL-8 and its clinical relevance in patients with fibromyalgia ( FM ) who fulfilled clearly defined inclusion and exclusion criteria and underwent a 3-week in patients multidisciplinary pain therapy . Methods IL-8 in sera was measured in 20 patients with FM and 80 healthy participants at 4 fixed time points : at the beginning of the study , at 10 days , 21 days , and 6 months , respectively . Pain intensity , back function , depression , nicotine/alcohol consumption , and medication were assessed in the patient group and correlated with IL-8 levels . Results Before and during the inpatient therapy , the serum level of IL-8 was significantly higher in patients with FM compared with controls ( P<0.001 ) , but did not correlated with pain intensity and medication . Already at T1 there was a significant reduction of IL-8 serum level ( P=0.023 ) in patient group . Six months after multidisciplinary pain therapy , IL-8 serum level in FM patients was still significantly higher than controls ( P=0.044 ) but reduced approximately to normal range and correlated significantly negatively with pain intensity ( r=−0.782 , P=0.001 ) . Patients with FM had significantly less pain ( P<0.001 ) and better back function ( P<0.001 ) at day 2 than at day 0 . In addition , in patients with FM , IL-8 serum level correlated with nicotine consumption ( r=0.471 , P=0.042 ) . Conclusions Our results suggest that IL-8 level contributes in patients with FM whose pain intensity and back function can be improved under influence of multidisciplinary pain therapy without need of an anti-IL-8 therapy Introduction Severe fatigue is a major health problem in fibromyalgia ( FM ) . Obesity is common in FM , but the influence of adipokines and growth factors is not clear . The aim was to examine effects of exercise on fatigue , in lean , overweight and obese FM patients . Methods In a longitudinal study , 48 FM patients ( median 52 years ) exercised for 15 weeks . Nine patients were lean ( body mass index , BMI 18.5 to 24.9 ) , 26 overweight ( BMI 25 to 29.9 ) and 13 obese . Fatigue was rated on a 0 to 100 mm scale ( fibromyalgia impact question naire [ FIQ ] fatigue ) and multidimensional fatigue inventory ( MFI-20 ) general fatigue ( MFIGF ) . Higher levels in FIQ fatigue and MFIGF indicate greater degree of fatigue . Free and total IGF-1 , neuropeptides , adipokines were determined in serum and cerebrospinal fluid ( CSF ) . Results Baseline FIQ fatigue correlated negatively with serum leptin ( r = -0.345 ; P = 0.016 ) and nerve growth factor ( NGF ; r = -0.412 ; P = 0.037 ) . In lean patients , baseline MFIGF associated negatively with serum resistin ( r = -0.694 ; P = 0.038 ) . FIQ Fatigue associated negatively with CSF resistin ( r = -0.365 ; P = 0.073 ) . Similarly , FIQ fatigue ( r = -0.444 ; P = 0.026 ) and MFIGF correlated negatively with CSF adiponectin ( r = -0.508 ; P = 0.01 ) . In lean patients , FIQ fatigue ( P = 0.046 ) decreased after 15 weeks . After 30 weeks , MFIGF decreased significantly in lean ( MFIGF : P = 0.017 ) , overweight ( MFIGF : P = 0.001 ) , and obese patients ( MFIGF : P = 0.016 ) . After 15 weeks , total IGF-1 increased in lean ( P = 0.043 ) patients . ∆Total IGF-1 differed significantly between lean and obese patients ( P = 0.010 ) . ∆Total IGF-1 related negatively with ∆MFIGF after 15 weeks ( r = -0.329 ; P = 0.050 ) . After 30 weeks , ∆FIQ fatigue negatively correlated with ∆NGF ( r = -0.463 ; P = 0.034 ) and positively with ∆neuropeptide Y ( NPY ) ( r = 0.469 ; P = 0.032 ) . Resistin increased after 30 weeks ( P = 0.034 ) . ∆MFIGF correlated negatively with ∆resistin ( r = -0.346 ; P = 0.031 ) , being strongest in obese patients ( r = -0.815 ; P = 0.007 ) . In obese patients , ∆FIQ fatigue after 30 weeks correlated negatively with ∆free IGF-1 ( r = -0.711 ; P = 0.032 ) . Conclusions Exercise reduced fatigue in all FM patients , this effect was achieved earlier in lean patients . Baseline levels of resistin in both serum and CSF associated negatively with fatigue . Resistin was increased after the exercise period which correlated with decreased fatigue . Changes in IGF-1 indicate similar long-term effects in obese patients . This study shows reduced fatigue after moderate exercise in FM and indicates the involvement of IGF-1 and resistin in these beneficial effects . Trial registration Clinical Trials.gov : The purpose of this study was to investigate the clinical effects of balneotherapy in \n Output:\n " }, { "from": "agent", "value": "After exercise , multidisciplinary , or dietary interventions in FM patients , interleukin ( IL ) expression appeared reduced , specifically serum IL-8 and IL-6 ( spontaneous , lipopolysaccharide (LPS)-induced , or serum ) .\nFurthermore , the changes to insulin-like growth factor 1 ( IGF-1 ) levels might indicate a beneficial role for fatigue in obese FM patients .\nIn contrast , evidence of changes in neuropeptide and CRP levels seemed inconsistent .\nConclusion Despite minimal evidence , our findings indicate that exercise interventions might act as an anti-inflammatory treatment in FM patients and ameliorate inflammatory status , especially for pro-inflammatory cytokines ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Background This study was conducted to investigate whether the most common injuries in soccer could be prevented , and to determine if a simple question naire could identify players at increased risk . Hypothesis Introduction of targeted exercise programs to male soccer players with a history of previous injury or reduced function in the ankle , knee , hamstring , or groin will prevent injuries . Study Design R and omized controlled trial ; Level of evidence , 2 . Methods A total of 508 players representing 31 teams were included in the study . A question naire indicating previous injury and /or reduced function as inclusion criteria was used to divide the players into high-risk ( HR ) ( 76 % ) and low-risk ( LR ) groups . The HR players were r and omized individually into an HR intervention group or HR control group . Results A total of 505 injuries were reported , sustained by 56 % of the players . The total injury incidence was a mean of 3.2 ( 95 % confidence interval [ CI ] , 2.5–3.9 ) in the LR control group , 5.3 ( 95 % Cl , 4.6–6.0 ) in the HR control group ( P = .0001 vs the LR control group ) , and 4.9 ( 95 % Cl , 4.3–5.6 ) in the HR intervention group ( P = .50 vs the HR control group ) . For the main outcome measure , the sum of injuries to the ankle , knee , hamstring , and groin , there was also a significantly lower injury risk in the LR control group compared with the 2 other groups , but no difference between the HR intervention group and the HR control group . Compliance with the training programs in the HR intervention group was poor , with only 27.5 % in the ankle group , 29.2 % in the knee group , 21.1 % in the hamstring group , and 19.4 % in the groin defined as having carried out the minimum recommended training volume . Conclusion The players with a significantly increased risk of injury were able to be identified through the use of a question naire , but player compliance with the training programs prescribed was low and any effect of the intervention on injury risk could not be detected Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background A soccer-specific balance training has been shown to decrease injury incidence of the anterior cruciate ligament and ankle sprains in r and omized controlled trials . However , hamstring injuries and tendinopathy remain significant issues in soccer . Hypothesis Proprioceptive training can reduce the incidence of hamstring muscle injuries and tendinopathy in elite soccer . There is a dose-effect relationship between balance training duration and injury incidence . Study Design Cohort study ; Level of evidence , 3 . Methods Twenty-four elite female soccer players ( body mass index , 21.7 ± 1.2 ; age , 21 ± 4 years ) of a German premier league soccer team were prospect ively included . Starting in January 2004 , an additional soccer-specific proprioceptive multistation training was initiated over 3 years . Injury data /1000 hours of exposure with documentation of all occurred injuries , detailed training , and match exposure data as well as time loss data were 100 % complete . Results At the end of the 3-year proprioceptive balance training intervention , noncontact hamstring injury rates were reduced from 22.4 to 8.2/1000 hours ( P = .021 ) , patellar tendinopathy from 3.0 to 1.0/1000 hours ( P = .022 ) , and Achilles tendinopathy from 1.5 to 0.0/1000 hours ( P = .035 ) . There was no effect of balance training on contact injuries . Mean time loss of all assessed injuries significantly decreased from 14.4 days during the control period to 1.5 days during intervention periods ( P = .003 ) . The more minutes of balance training performed , the lower the rate of overall injuries ( r = −0.185 , P = .001 ) , hamstring injuries ( r = −0.267 , P = .003 ) , patellar tendinopathy ( r = −0.398 , P = .02 ) , and gastrocnemius strains ( r = −0.342 , P = .002 ) . Conclusion Soccer-specific balance training ( protective balancing ) can reduce noncontact hamstring injuries and patellar and Achilles tendinopathy . A dose-effect relationship between duration of balance training and injury incidence is evident . A proprioceptive training program reduced the rehabilitation time in noncontact injuries , which warrants further investigation Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies Background : Muscle injuries constitute a large percentage of all injuries in football . Purpose : To investigate the incidence and nature of muscle injuries in male professional footballers . Study Design : Cohort study ; Level of evidence , 2 . Methods : Fifty-one football teams , comprising 2299 players , were followed prospect ively during the years 2001 to 2009 . Team medical staff recorded individual player exposure and time-loss injuries . The first-team squads of 24 clubs selected by the Union of European Football Associations as belonging to the best European teams , 15 teams of the Swedish First League , and another 15 European teams playing their home matches on artificial turf pitches were included . A muscle injury was defined as “ a traumatic distraction or overuse injury to the muscle leading to a player being unable to fully participate in training or match play . ” Results : In total , 2908 muscle injuries were registered . On average , a player sustained 0.6 muscle injuries per season . A squad of 25 players can thus expect about 15 muscle injuries per season . Muscle injuries constituted 31 % of all injuries and caused 27 % of the total injury absence . Ninety-two percent of all muscle injuries affected the 4 major muscle groups of the lower limbs : hamstrings ( 37 % ) , adductors ( 23 % ) , quadriceps ( 19 % ) , and calf muscles ( 13 % ) . Sixteen percent of the muscle injuries were reinjuries . These reinjuries caused significantly longer absences than did index injuries . The incidence of muscle injury increased with age . When separated into different muscle groups , however , an increased incidence with age was found only for calf muscle injuries and not for hamstring , quadriceps , or hip/groin strains . Conclusion : Muscle injuries are a substantial problem for players and their clubs . They constitute almost one third of all time-loss injuries in men ’s professional football , and 92 % of all injuries affect the 4 big muscle groups in the lower limbs ‘ More research is needed ’ is a most unhelpful conclusion for the clinician reader of a systematic review . Clinicians look to research ers for the ‘ research evidence ’ part of Professor Sackett ’s ‘ three circles ’ of evidence -based practice .1 The clinician can not ignore the patient in front of him or her just because there is no evidence from systematic review s or r and omised controlled trials ( RCTs ): ‘ Kindly forget about your shoulder problem , until we have better research to tell me what to do ’ ? This will not do ! In this editorial , we share three practical tips for authors synthesis ing lower level evidence in systematic review s , when high- quality RCTs are absent . Our goal is to help authors help clinicians help patients . Consider the patient who plays tennis and presents with shoulder pain . Right now , the clinician who is seeking RCT evidence on how to progress from impairment-focused tasks in neutral shoulder positions to high-level , sport-specific tasks will be disappointed . Being able to function in shoulder elevation positions above The purpose was to test the effect of eccentric strength training and flexibility training on the incidence of hamstring strains in soccer . Hamstring strains and player exposure were registered prospect ively during four consecutive soccer seasons ( 1999 - 2002 ) for 17 - 30 elite soccer teams from Icel and and Norway . The first two seasons were used as baseline , while intervention programs consisting of warm-up stretching , flexibility and /or eccentric strength training were introduced during the 2001 and 2002 seasons . During the intervention seasons , 48 % of the teams selected to use the intervention programs . There was no difference in the incidence of hamstring strains between teams that used the flexibility training program and those who did not [ relative risk (RR)=1.53 , P=0.22 ] , nor was there a difference compared with the baseline data ( RR=0.89 , P=0.75 ) . The incidence of hamstring strains was lower in teams who used the eccentric training program compared with teams that did not use the program ( RR=0.43 , P=0.01 ) , as well as compared with baseline data for the same intervention teams ( RR=0.42 , P=0.009 ) . Eccentric strength training with Nordic hamstring lowers combined with warm-up stretching appears to reduce the risk of hamstring strains , while no effect was detected from flexibility training alone . These results should be verified in r and omized clinical trials PURPOSE To analyze the effect of an eccentric-overload training program ( ie , half-squat and leg-curl exercises using flywheel ergometers ) with individualized load on muscle-injury incidence and severity and performance in junior elite soccer players . METHODS Thirty-six young players ( U-17 to U-19 ) were recruited and assigned to an experimental ( EXP ) or control group ( CON ) . The training program consisted of 1 or 2 sessions/wk ( 3 - 6 sets with 6 repetitions ) during 10 wk . The outcome measured included muscle injury ( incidence per 1000 h of exposure and injury severity ) and performance tests ( countermovement jump [ CMJ ] , 10-m and 20-m sprint test ) . RESULTS Between-groups results showed a likely ( ES : 0.94 ) lower number of days of absence per injury and a possible decrement of incidence per 1000 h of match play in EXP than in CON . Regarding muscle performance , a substantial better improvement ( likely to very likely ) was found in 20-m sprint time ( ES : 0.37 ) , 10-m flying-sprint time ( ES : 0.77 ) , and CMJ ( ES : 0.79 ) for EXP than for CON . Within-group analysis showed an unclear effect in each variable in CON . Conversely , substantial improvements were obtained in CMJ ( ES : 0.58 ) , 20-m sprint time ( ES : 0.32 ) , 10-m flying-sprint time ( ES : 0.95 ) , and injury severity ( ES : 0.59 ) in EXP . Furthermore , a possible decrement in total injury incidence was also reported in EXP . CONCLUSIONS The eccentric-based program led to a reduction in muscle-injury incidence and severity and showed improvements in common soccer tasks such as jumping ability and linear-sprinting speed R and omised controlled trials are the best way to compare the effectiveness of different interventions . Only r and omised trials allow valid inferences of cause and effect . Only r and omised trials have the potential directly to affect patient care — occasionally as single trials but more often as the body of evidence from several trials , whether or not combined formally by meta- analysis . It is thus entirely reasonable to require higher st and ards for papers reporting r and omised trials than those describing other types of study . Like all studies , r and omised trials are open to bias if done badly.1 It is thus essential that r and omised trials are done well and reported adequately . Readers should not have to infer what was probably done , they should be told explicitly . Proper methodology should be used and be seen to have been used . Yet review s of published trials have consistently found major deficiencies in reporting,2 3 4 making the task Research and discussion s about injury rates and their prevention in elite football is one of the hottest topics in the medical and sport science literature . Over the past years , there has been an explosion of the number of publications , including surveys,1 observational , retrospective or prospect ive2 studies , training interventions and various types of expert opinions and commentaries.3 This array of information are likely useful to improve our underst and ing of what the best practice s may be and , in turn , increase our ability to better prepare , manage and treat players . However , a recent survey has shown that 83 % of UEFA clubs do not follow evidence d-based prevention programmes.1 It was also shown that hamstring injuries kept increasing over the last 13 years.2 Taken together , those two papers may suggest that the majority of elite club practitioners likely disregard research findings 1 and may therefore be the one to be blamed for those increased injury rates.2 Making supporting staff and coaches responsible for those injuries is easy , especially when considering their perceived typical personality traits ( ie , so-called type 2,4 high egos and little open-mindedness and willingness to learn—‘why could they be bothered applying the new study findings ? ’ ) . While this may be true sometimes , the reality is that The primary purpose of this study was to evaluate whether a preseason strength training programme for the hamstring muscle group - emphasising eccentric overloading - could affect the occurrence and severity of hamstring injuries during the subsequent competition season in elite male soccer players . Thirty players from two of the best premier- \n Output:\n " }, { "from": "agent", "value": "We found limited scientific evidence to support exercise-based strategies to prevent muscle injury in elite footballers ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: BACKGROUND Plasma levels of insulin-like growth factor-I ( IGF-I ) have been associated with the risk of prostate cancer . However , the association of IGF-I with specific tumor stage and grade at diagnosis , which correlate with risk of recurrence and mortality , has not been studied rigorously . To determine whether plasma levels of IGF-I and its main circulating binding protein , IGF binding protein-3 ( IGFBP-3 ) , predict more aggressive forms of prostate cancer , we investigated the association between plasma levels of each and specific stages and grade s of prostate cancer . METHODS We examined 530 case patients and 534 control subjects in a nested case-control study in the prospect i ve Physicians ' Health Study . Patients with prostate cancer diagnosed from 1982 through 1995 were matched to control subjects by age and smoking status . IGF-I and IGFBP-3 were measured in prospect ively collected plasma sample s. Conditional logistic regression models were used to estimate the relative risks ( RRs ) for prostate cancer associated with IGF-I and IGFBP-3 , stratified on grade ( Gleason score > or = 7 versus < 7 ) and stage ( early = stage A or B prostate cancer versus advanced = stage C or D prostate cancer ) . All statistical tests were two-sided . RESULTS Plasma levels of IGF-I and IGFBP-3 were predictors of advanced-stage prostate cancer ( RR = 5.1 , 95 % confidence interval [ CI ] = 2.0 to 13.2 for highest versus lowest quartiles of IGF-I ; RR = 0.2 , 95 % CI = 0.1 to 0.6 for highest versus lowest quartiles of IGFBP-3 ) but not of early-stage prostate cancer . Neither was differentially associated with Gleason score . Men with high IGF-I levels and low IGFBP-3 levels had an RR for advanced-stage prostate cancer of 9.5 ( 95 % CI = 1.9 to 48.4 ) compared with men with low levels of both . Combining IGF-I and IGFPB-3 measurements with a st and ard prostate-specific antigen ( PSA ) measurement for prostate cancer screening increased the specificity ( from 91 % to 93 % ) but decreased sensitivity ( from 40 % to 36 % ) compared with measurement of PSA alone . CONCLUSIONS Circulating levels of IGF-I and IGFBP-3 may predict the risk of developing advanced-stage prostate cancer , but their utility for screening patients with incident prostate cancer may be limited 5 Background : It is largely unknown whether prostate-specific antigen at first date of testing predicts long-term risk of prostate cancer incidence and mortality in the general population . We tested the hypothesis that baseline prostate-specific antigen levels predict long-term risk of prostate cancer incidence and mortality . METHODS Using a prospect i ve study , we examined 4383 20 - 94 year old men from the Danish general population followed in the Copenhagen City Heart Study from 1981 through 2009 . Prostate-specific antigen was measured in plasma sample s obtained in 1981 - 83 . RESULTS During 28 years of follow-up , 170 men developed prostate cancer and 94 died from prostate cancer . Median follow-up was 18 years ( range 0.5 - 28 years ) . For prostate cancer incidence , the subhazard ratio was 3.0 ( 95 % confidence interval ( CI ) 1.9 - 4.6 ) for a prostate-specific antigen level of 1.01 - 2.00 ng/ml , 6.8 ( 4.2 - 11 ) for 2.01 - 3.00 ng/ml , 6.6 ( 3.4 - 13 ) for 3.01 - 4.00 ng/ml , 16 ( 10.4 - 25 ) for 4.01 - 10.00 ng/ml , and 57 ( 32 - 104 ) for > 10.00 ng/ml versus 0.01 - 1.00 ng/ml .. For prostate cancer mortality , corresponding subhazard ratios were 2.2 ( 1.3 - 3.9 ) , 5.1 ( 2.8 - 9.0 ) , 4.2 ( 1.8 - 10 ) , 7.0 ( 3.8 - 14 ) , and 14 ( 6.0 - 32 ) . For men with prostate-specific antigen levels of 0.01 - 1.00 ng/ml , absolute 10-year risk of prostate cancer was 0.6 % for age < 45 years , 0.7 % for 45 - 49 years , 1.1 % for 50 - 54 years , 1.2 % for 55 - 59 years , 1.3 % for 60 - 64 years , 1.1 % for 65 - 69 years , 1.3 % for 70 - 74 years , and 1.5 % for age≥75 years ; corresponding values for prostate-specific antigen levels > 10.00 ng/ml were 35 % , 41 % , 63 % , 71 % , 77 % , 69 % , 75 % , and 88 % , respectively . CONCLUSIONS Stepwise increases in prostate-specific antigen at first date of testing predicted a 3 - 57 fold increased risk of prostate cancer , a 2 - 16 fold increased risk of prostate cancer mortality , and a 35 - 88 % absolute 10-year risk of prostate cancer in those with prostate-specific antigen levels > 10.00 ng/ml . Equally important , absolute 10-year risk of prostate cancer in those with levels 0.01 - 1.00 ng/ml was only 0.6 - 1.5 % BACKGROUND Risk-stratified screening for prostate cancer ( PCa ) with prostate-specific antigen ( PSA ) testing incorporating genetic variants has received some attention but has been scarcely investigated . We developed a model to stratify the Finnish population by different risk profiles related to genetic variants to optimize the screening policy . METHODS Data from the Finnish r and omized controlled trial on screening for PCa with PSA testing were used to estimate a six-state Markov model of disease progression . Blood sample s from Finnish men were used to assess the risk of PCa related to three genetic variants ( rs4242382 , rs138213197 , and rs200331695 ) . A risk score-based approach combined with a series of computer simulation models was applied to optimize individual screening policies . RESULTS The 10-year risk of having progressive prostate cancer detected ranged from 43 % in the top 5 % risk group to approximately 11 % in the bottom half of the population . Using the median group , with screening every four years beginning at 55 years-old , as the reference group , the recommended age beginning screening was approximately 47 years-old for the top 5 % risk group and 55 years-old for those in the lower 60 % risk group . The recommended interscreening interval has been shortened for individuals in the high risk group . The increased availability of genomic information allows the proposed multistate model to be more discriminating with respect to risk stratification and the suggested screening policy , particularly for the lowest risk groups- . -- CONCLUSIONS A multi-state genetic variant-based model was developed for further application to population risk stratification to optimize the interscreening interval and the age at which to begin screening for PSA . A small sub-group of the population is likely to benefit from more intensive screening with early start and short interval , while half of the population is unlikely to benefit from such protocol ( compared with four-year interval after age 55 years ) Summary In this paper , we develop a Markov chain model to estimate parameters pertaining to the natural history of nasopharyngeal carcinoma ( NPC ) . The model is of progression from no disease to Epstein – Barr virus ( EBV ) infection , pre clinical screen-detectable tumour and clinical tumour . We derive tentative estimates of the parameters of the model , based on limited published data , to assess the efficacy of serum screening in conjunction with clinical assessment ( indirect mirror examination for NPC ) , for example the average duration of the pre clinical screen-detectable phase is estimated as 3.1 years . We further apply these parameters to a hypothetical screening trial in the Hong Kong population to assess the efficacy of serum screening with clinical assessment by different combinations of screening regime . Results suggest : ( 1 ) there is no substantial difference between 3-yearly and 6-yearly serum screening ; and ( 2 ) within the same serum screening regime annual and 3-yearly clinical assessment can prevent 33 % and 28 % of deaths from NPC respectively . Prediction of deaths and surrogate end points can be used to estimate the required sample size and duration for design ing a r and omized trial of screening for NPC . Based on these findings and power projections , we suggest a design for a r and omized trial in a high incidence area such as Hong Kong BACKGROUND The aim of the present study was to evaluate the future cumulative risk of prostate cancer in relation to levels of prostate-specific antigen ( PSA ) in blood and to determine whether this information could be used to individualize the PSA testing interval . METHODS The study included 5855 of 9972 men ( aged 50 - 66 years ) who accepted an invitation to participate in a prospect i ve , r and omized study of early detection for prostate cancer . We used a protocol based on biennial PSA measurements starting from 1995 and 1996 . Men with serum PSA levels of 3.0 ng/mL or more were offered prostate biopsies . RESULTS Among the 5855 men , 539 cases of prostate cancer ( 9.2 % ) were detected after a median follow-up of 7.6 years ( up to July 1 , 2003 ) . Cancer detection rates during the follow-up period in relation to PSA levels were as follows : 0 to 0.49 ng/mL , 0 % ( 0/958 ) ; 0.50 to 0.99 ng/mL , 0.9 % ( 17/1992 ) ; 1.00 to 1.49 ng/mL , 4.7 % ( 54/1138 ) ; 1.50 to 1.99 ng/mL , 12.3 % ( 70/571 ) ; 2.00 to 2.49 ng/mL , 21.4 % ( 67/313 ) ; 2.50 to 2.99 ng/mL , 25.2 % ( 56/222 ) ; 3.00 to 3.99 ng/mL , 33.3 % ( 89/267 ) ; 4.00 to 6.99 ng/mL , 38.9 % ( 103/265 ) ; 7.00 to 9.99 ng/mL , 50.0 % ( 30/60 ) ; and for men with an initial PSA of 10.00 ng/mL or higher , 76.8 % ( 53/69 ) . Not a single case of prostate cancer was detected within 3 years in 2950 men ( 50.4 % of the screened population ) with an initial PSA level less than 1 ng/mL. CONCLUSIONS Retesting intervals should be individualized on the basis of the PSA level , and the large group of men with PSA levels of less than 1 ng/mL can safely be scheduled for a 3-year testing interval We followed our initial genome-wide association study ( GWAS ) of 527,869 SNPs on 1,172 individuals with prostate cancer and 1,157 controls of European origin — nested in the Prostate , Lung , Colorectal , and Ovarian ( PLCO ) Cancer Screening Trial prospect i ve study —by testing 26,958 SNPs in four independent studies ( total of 3,941 cases and 3,964 controls ) . In the combined joint analysis , we confirmed three previously reported loci ( two independent SNPs at 8q24 and one in HNF1B ( formerly known as TCF2 on 17q ) ; P < 10−10 ) . In addition , loci on chromosomes 7 , 10 ( two loci ) and 11 were highly significant ( between P < 7.31 × 10−13 and P < 2.14 × 10−6 ) . Loci on chromosome 10 include MSMB , which encodes β-microseminoprotein , a primary constituent of semen and a proposed prostate cancer biomarker , and CTBP2 , a gene with antiapoptotic activity ; the locus on chromosome 7 is at JAZF1 , a transcriptional repressor that is fused by chromosome translocation to SUZ12 in endometrial cancer . Of the nine loci that showed highly suggestive associations ( P < 2.5 × 10−5 ) , four best fit a recessive model and included c and i date susceptibility genes : CPNE3 , IL16 and CDH13 . Our findings point to multiple loci with moderate effects associated with susceptibility to prostate cancer that , taken together , in the future may predict high risk in select individuals As with wide-spread use of prostate cancer ( Pca ) screening with prostate-specific antigen testing , overdetection has increasingly gained attention . The authors aim ed to estimate absolute risk of overdetection ( RO ) in Pca screening with various interscreening intervals and ages at start of screening . We estimated age-specific pre clinical incidence rates ( per 100,00 \n Output:\n " }, { "from": "agent", "value": "4 ) Conclusions : Gene‒PSA-guided personalized screening for PrCa leads to fewer unnecessary PSA tests without compromising the benefits of mortality reduction ( as happens with the universal screening program )" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: OBJECTIVE The present study examined the effects of emotional disclosure ( ED ) intervention on both disease severity and quality of life in patients with psoriasis . METHODS Fifty-nine patients were recruited ( mean age , 50 years ; 32 men and 27 women ; mean length of diagnosis , 22 years ) . Individuals were r and omly assigned to receive ED intervention or st and ard control writing intervention . Disease severity , quality of life , and mood were assessed at baseline and at 2 , 8 , and 12 weeks postintervention . RESULTS Disease severity and quality of life improved in both groups over the follow-up period . Preliminary analysis suggested no differences in the magnitude of improvement between the groups . However , predictors of improvement were found to differ . Disease severity on Week 12 was predicted by changes in mood in intervention patients and seasonal variation in control patients . In contrast , quality of life on Week 12 was predicted by baseline quality of life in intervention patients , while seasonal variation approached significance for control patients . CONCLUSIONS Changes in mood following ED predicted improvements in disease severity in patients with psoriasis . However , the degree of improvement did not differ between intervention and control patients Objective : Patients with somatic conditions , such as psoriasis , frequently suffer from high burden of their disease in daily life and might benefit from internet-based cognitive behavioral therapy ( ICBT ) tailored to their adjustment problems . The aim of this multicenter r and omized controlled trial was to examine the effects of therapist-guided , individually tailored ICBT in a clinical sample of patients with psoriasis . Methods : A total of 131 patients with psoriasis , who were screened for a psychological risk profile , were r and omized to either care as usual ( CAU , n = 66 ) or ICBT in addition to CAU ( n = 65 ) . Participants filled out st and ardized self-report question naires assessing physical and psychological functioning and impact on daily activities at baseline , posttreatment assessment , and 6-month follow-up . Results : In covariate-controlled linear mixed-model analyses , significantly larger improvements in ICBT compared to CAU were found in the primary outcomes physical functioning ( p = 0.03 , d = 0.36 ) and impact on daily activities ( p = 0.04 , d = 0.35 ) , but not in psychological functioning ( p = 0.32 ) , up to 6 months after treatment compared to baseline . In explorative analyses , the working alliance measured at the beginning of ICBT treatment predicted improved physical ( p = 0.02 ) and psychological ( p < 0.001 ) outcomes . Conclusions : Results underline the promise of therapist-guided , individually tailored ICBT to improve physical functioning and reduce the impact of psoriasis on daily activities in patients with a psychological risk profile . Establishing a good therapeutic relationship early on may be an important factor that influences treatment outcomes in personalized ICBT interventions . Further research is needed to evaluate ICBT effectiveness in additional sample s and to explore its underlying mechanisms Background Data evaluating the impact of objective ly measured psoriasis severity on type 2 diabetes mellitus ( T2DM ) risk are lacking . Objective To determine the risk for T2DM in patients with psoriasis compared with that in adults without psoriasis , stratified by categories of directly assessed body surface area ( BSA ) affected by psoriasis . Methods A prospect i ve , population ‐based , cohort study from the United Kingdom in which 8124 adults with psoriasis and 76,599 adults without psoriasis were followed prospect ively for approximately 4 years . Results There were 280 incident cases of diabetes in the psoriasis group ( 3.44 % ) and 1867 incident cases of diabetes in those without psoriasis ( 2.44 % ) . After adjustment for age , sex and body mass index , the hazard ratios for development of incident diabetes were 1.21 ( 95 % confidence interval [ CI ] , 1.01‐1.44 ) , 1.01 ( 95 % CI , 0.81‐1.26 ) , and 1.64 ( 95 % CI , 1.23‐2.18 ) in the groups with 2 % or less of their BSA affected , 3 % to 10 % of their BSA affected , and 10 % or more of their BSA affected compared with in the groups without psoriasis , respectively ( P = .004 for trend ) . Worldwide , we estimate an additional 125,650 new diagnoses of T2DM per year in patients with psoriasis as compared with in those without psoriasis . Limitations Relatively short‐term follow‐up and exclusion of prevalence cases , which may have masked associations in patients with less extensive psoriasis . Conclusion Clinicians may measure BSA affected by psoriasis to target diabetes prevention efforts for patients with psoriasis BACKGROUND AND OBJECTIVES The treatment of negative symptoms in schizophrenia is a major challenge for mental health care . One r and omized controlled trial found that cognitive therapy for low-functioning patients reduced avolition and improved functioning , using an average of 50.5 treatment sessions over the course of 18 months . The aim of our current pilot study was to evaluate whether 20 sessions of Cognitive Behavioral Therapy for negative symptoms ( CBT-n ) would reduce negative symptoms within 6 months . Also , we wanted to test the cognitive model of negative symptoms by analyzing whether a reduction in dysfunctional beliefs mediated the effects on negative symptoms . METHOD In an open trial 21 adult out patients with a schizophrenia spectrum disorder with negative symptoms received an average of 17.5 sessions of CBT-n . At baseline and end-of-treatment , we assessed negative symptoms ( PANSS ) and dysfunctional beliefs about cognitive abilities , performance , emotional experience , and social exclusion . Bootstrap analysis tested mediation . RESULTS The dropout rate was 14 % ( three participants ) . Intention-to-treat analyses showed a within group effect size of 1.26 on negative symptoms ( t = 6.16 , | Sig = 0.000 ) . Bootstrap analysis showed that dysfunctional beliefs partially mediated the change . LIMITATIONS The uncontrolled design induced efficacy biases . Also , the sample was relatively small , and there were no follow-up assessment s. CONCLUSIONS CBT-n may be effective in reducing negative symptoms . Also , patients reported fewer dysfunctional beliefs about their cognitive abilities , performance , emotional experience , and social exclusion , and this reduction partially mediated the change in negative symptoms . The reductions were clinical ly important . However , larger and controlled trials are needed OBJECTIVE Patient advocacy groups such as the National Psoriasis Foundation ( NPF ) serve as representatives of those affected by disease and provide information about the condition . Our objective was to assess the extent to which NPF members differ from nonmember patients with psoriasis in their knowledge and use of therapies . PARTICIPANTS Using r and om-digit dialing , we identified and interviewed patients with psoriasis in the general US population . R and omly selected NPF members were also interviewed . MAIN OUTCOME MEASURES Multivariate logistic regression models were used to estimate differences ( odds ratios and 95 % confidence intervals ) in demographic and clinical characteristics and in awareness and use of therapies between members and others diagnosed as having psoriasis . RESULTS Of 601 individuals with psoriasis identified from the general population survey , 185 provided a second interview and were defined as nonmembers . We interviewed 289 r and omly selected members of the NPF . Although members were significantly older and wealthier and had more extensive disease , they reported the disease to be significantly less of a burden and were more satisfied with therapy than others affected . Compared with nonmembers , members were significantly more likely to have heard of and used most of the 10 therapies assessed . However , the proportion of respondents who were aware of a therapy and who also used it did not differ between groups . CONCLUSION Members of the NPF are better informed and more satisfied with available treatment options than nonmember affected patients Increasing data suggests that there is a connection between stress and the appearance of psoriasis symptoms . We therefore performed a clinical trial enrolling 40 participants who were r and omly allocated to either an 8-week cognitive-behavioural therapy ( CBT ) ( treatment group ) plus narrow-b and UVB phototherapy or to an 8-week course of only narrow-b and UVB phototherapy ( control group ) . We evaluated the clinical severity of psoriasis ( PASI ) , General Health Question naire (GHQ)-12 , Skindex-29 and State-Trait Anxiety Inventory ( STAI ) at baseline and by the end of the study . Sixty-five percent of patients in the treatment group achieved PASI75 compared with 15 % of st and ard UVB patients ( p = 0.007 ) . GHQ-12 cases were reduced from 45 % to 10 % in the treatment group and from 30 % to 20 % in the control group ( p = 0.05 ) . The Skindex-29 emotional domain showed a significant improvement in the CBT/biofeedback group compared with control patients ( -2.8 points , p = 0.04 ) . This study shows that an adjunctive 8-week intervention with CBT combined with biofeedback increases the beneficial effect of UVB therapy in the overall management of psoriasis , reduces the clinical severity of psoriasis , improving quality of life and decreases the number of minor psychiatric disorders Background : The evidence for efficacy of psychoeducational interventions in psoriasis is not well research ed . Objective : The objective of this study was to assess the benefits of a group , multi-professional , psychoeducational training in psoriasis . Material s and Methods : Adults with moderate-to-severe psoriasis were r and omized into psychoeducational intervention plus treatment ( intervention arm [ IA ] ) and treatment as usual alone ( control arm [ CA ] ) groups using r and om number tables . The primary efficacy measures were mean changes in Psoriasis Area Severity Index ( PASI ) and Dermatology Life Quality Index ( DLQI ) at 6months from the end of intervention . The secondary efficacy measures were the mean changes in the WHO-5 well-being index ( WHO-5 ) and the subsets of the patient health question naire ( PHQ ) , namely , PHQ-9 , generalized anxiety disorder (GAD)-7 , and PHQ-15 . Data were analyzed by intention-to-treat analysis . Results : One-hundred and three participants were r and omized into IA ( n = 54 ) and CA ( n = 49 ) . The prevalence of psychiatric disorders in the entire population was 26.2 % and was similar in both groups . Following intervention , there was statistically significant improvement in the mean scores in PASI , DLQI , and WHO-5 in the IA unlike that seen in the CA . There was statistically significant improvement in PHQ-9 scores in IA and CA . The scores on PHQ-15 and GAD-7 did not show any change . Intergroup comparisons showed that PASI was reduced significantly in IA as compared to CA . More participants in CA dropped out of the study than in the IA . Limitations : Modest sample size and lack of blinding of the participants and the administrators were the limitations of this study . Conclusion : Group psychoeducational intervention result ed in overall improvement in both clinical and psychological outcome measures in psoriasis patients BACKGROUND Case reports have indicated that psychologic treatments may have a beneficial effect on psoriasis activity . OBJECTIVE Our purpose was to further investigate the hypothesis that psychologic intervention has a beneficial effect on psoriasis activity in a blinded , controlled manner . METHODS Fifty-one patients with psoriasis vulgaris were r and omly assigned to a treatment or a control group . Patients in the treatment group participated in seven individual psychotherapy sessions in 12 weeks . Intervention techniques included stress management , guided imagery , and relaxation . The Psoriasis Area Severity Index ( PASI ) , Total Sign Score ( TSS ) , and Laser Doppler Skin Blood Flow ( LDBF ) of a selected reference plaque was measured in a blinded fashion at baseline ( week 0 ) , week 4 , week 8 , and after treatment ( week 12 ) . RESULTS Slight , but significant , changes in TSS and LDBF were found in the treatment group but not in the control group . When analyses were performed for both groups separately , the treatment group displayed significant reductions for all three psoriasis activity measures , whereas no changes were seen in the control group . CONCLUSION Our preliminary results suggest that psychologic intervention may have a moderate beneficial effect on psoriasis activity BACKGROUND Depression is a common mental health condition that has been associated with psoriasis . In the absence of prospect i ve data , it remains unclear whether depression precedes psoriasis as a risk factor . OBJECTIVES To examine the association between depression and the risk of new-onset psoriasis . METHODS A prospect i ve cohort of 86 880 US female nurses , The Nurses ' Health Study II , was followed up from 1993 to 2005 . Participants reported anti-depressant use and completed the Mental Health Index ( MHI ) , a subscale of the Short-Form 36 in 1993 . The MHI assessed for depression and scores was categorized into four strata : 0 - 52 , 53 - 75 , 76 - 85 and 86 - 100 , with lower scores associated with increasing depressive symptoms . We excluded participants with a history of psoriasis prior to 1993 . A self-report of incident physician-diagnosed psoriasis constituted the main outcome \n Output:\n " }, { "from": "agent", "value": "Conclusion CBT is effective in the treatment of psoriasis in terms of area and severity reduction .\nSystemic treatment does not further enhance the efficacy of CBT .\nThe effect of the psychological intervention is stronger in patients with moderate-to-severe psoriasis" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: The circulating level of brain-derived neurotrophic factor ( BDNF ) is reduced in patients with major depression and type-2 diabetes . Because acute exercise increases BDNF production in the hippocampus and cerebral cortex , we hypothesized that endurance training would enhance the release of BDNF from the human brain as detected from arterial and internal jugular venous blood sample s. In a r and omized controlled study , 12 healthy sedentary males carried out 3 mo of endurance training ( n = 7 ) or served as controls ( n = 5 ) . Before and after the intervention , blood sample s were obtained at rest and during exercise . At baseline , the training group ( 58 + or - 106 ng x 100 g(-1 ) x min(-1 ) , means + or - SD ) and the control group ( 12 + or - 17 ng x 100 g(-1 ) x min(-1 ) ) had a similar release of BDNF from the brain at rest . Three months of endurance training enhanced the resting release of BDNF to 206 + or - 108 ng x 100 g(-1 ) x min(-1 ) ( P < 0.05 ) , with no significant change in the control subjects , but there was no training-induced increase in the release of BDNF during exercise . Additionally , eight mice completed a 5-wk treadmill running training protocol that increased the BDNF mRNA expression in the hippocampus ( 4.5 + or - 1.6 vs. 1.4 + or - 1.1 mRNA/ssDNA ; P < 0.05 ) , but not in the cerebral cortex ( 4.0 + or - 1.4 vs. 4.6 + or - 1.4 mRNA/ssDNA ) compared with untrained mice . The increased BDNF expression in the hippocampus and the enhanced release of BDNF from the human brain following training suggest that endurance training promotes brain health CONTEXT Many observational studies have shown that physical activity reduces the risk of cognitive decline ; however , evidence from r and omized trials is lacking . OBJECTIVE To determine whether physical activity reduces the rate of cognitive decline among older adults at risk . DESIGN AND SETTING R and omized controlled trial of a 24-week physical activity intervention conducted between 2004 and 2007 in metropolitan Perth , Western Australia . Assessors of cognitive function were blinded to group membership . PARTICIPANTS We recruited volunteers who reported memory problems but did not meet criteria for dementia . Three hundred eleven individuals aged 50 years or older were screened for eligibility , 89 were not eligible , and 52 refused to participate . A total of 170 participants were r and omized and 138 participants completed the 18-month assessment . INTERVENTION Participants were r and omly allocated to an education and usual care group or to a 24-week home-based program of physical activity . MAIN OUTCOME MEASURE Change in Alzheimer Disease Assessment Scale-Cognitive Subscale ( ADAS-Cog ) scores ( possible range , 0 - 70 ) over 18 months . RESULTS In an intent-to-treat analysis , participants in the intervention group improved 0.26 points ( 95 % confidence interval , -0.89 to 0.54 ) and those in the usual care group deteriorated 1.04 points ( 95 % confidence interval , 0.32 to 1.82 ) on the ADAS-Cog at the end of the intervention . The absolute difference of the outcome measure between the intervention and control groups was -1.3 points ( 95 % confidence interval,-2.38 to -0.22 ) at the end of the intervention . At 18 months , participants in the intervention group improved 0.73 points ( 95 % confidence interval , -1.27 to 0.03 ) on the ADAS-Cog , and those in the usual care group improved 0.04 points ( 95 % confidence interval , -0.46 to 0.88 ) . Word list delayed recall and Clinical Dementia Rating sum of boxes improved modestly as well , whereas word list total immediate recall , digit symbol coding , verbal fluency , Beck depression score , and Medical Outcomes 36-Item Short-Form physical and mental component summaries did not change significantly . CONCLUSIONS In this study of adults with subjective memory impairment , a 6-month program of physical activity provided a modest improvement in cognition over an 18-month follow-up period . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12605000136606 Background To examine the effect of multicomponent exercise program on memory function in older adults with mild cognitive impairment ( MCI ) , and identify biomarkers associated with improvement of cognitive functions . Methodology /Principal Findings Subjects were 100 older adults ( mean age , 75 years ) with MCI . The subjects were classified to an amnestic MCI group ( n = 50 ) with neuroimaging measures , and other MCI group ( n = 50 ) before the r and omization . Subjects in each group were r and omized to either a multicomponent exercise or an education control group using a ratio of 1∶1 . The exercise group exercised for 90 min/d , 2 d/wk , 40 times for 6 months . The exercise program was conducted under multitask conditions to stimulate attention and memory . The control group attended two education classes . A repeated- measures ANOVA revealed that no group × time interactions on the cognitive tests and brain atrophy in MCI patients . A sub- analysis of amnestic MCI patients for group × time interactions revealed that the exercise group exhibited significantly better Mini-Mental State Examination ( p = .04 ) and logical memory scores ( p = .04 ) , and reducing whole brain cortical atrophy ( p<.05 ) compared to the control group . Low total cholesterol levels before the intervention were associated with an improvement of logical memory scores ( p<.05 ) , and a higher level of brain-derived neurotrophic factor was significantly related to improved ADAS-cog scores ( p<.05 ) . Conclusions / Significance The results suggested that an exercise intervention is beneficial for improving logical memory and maintaining general cognitive function and reducing whole brain cortical atrophy in older adults with amnestic MCI . Low total cholesterol and higher brain-derived neurotrophic factor may predict improvement of cognitive functions in older adults with MCI . Further studies are required to determine the positive effects of exercise on cognitive function in older adults with MCI . Trial Registration UMIN-CTR UMIN000003662 ctr.cgi?function = brows&action = brows&type = summary & recptno = R000004436 & language = Objective : To examine the effects of aerobic exercise or vitamin B supplementation on cognitive function in older adults with mild cognitive impairment ( MCI ) . Design : R and omised placebo-controlled trial . Setting : General community . Participants : Community-dwelling adults aged 70–80 with MCI . Interventions : The 152 participants were r and omly assigned to two interventions : ( 1 ) a twice-weekly , group-based , moderate-intensity walking programme ( WP , n = 77 ) or a low-intensity placebo activity programme ( n = 75 ) for one year ; and ( 2 ) daily vitamin pill containing 5 mg folic acid , 0.4 mg vitamin B-12 , 50 mg vitamin B-6 ( FA/B12/B6 , n = 78 ) or placebo pill ( n = 74 ) for one year . Outcome measures : Cognitive function , measured with neuropsychological tests at baseline and after six and 12 months . Results : Median session attendance at the exercise programmes ( 25th–75th percentile ) was 63 % ( 2%–81 % ) and median compliance with taking pills ( 25th–75th percentile ) was 100 % ( 99%–100 % ) . Gender was an effect modifier . Intention-to-treat analysis revealed no main intervention effect for either intervention . In women in the WP , attention ( Stroop combination task ) improved by 0.3 seconds ( p = 0.04 ) and memory ( auditory verbal learning test ) by 0.04 words ( p = 0.06 ) with each percentage increase in session attendance . In men attending at least 75 % of the sessions , the WP improved memory ( β 1.5 ( 95 % CI : 0.1 to 3.0 ) words ) . Conclusion : The walking programme and /or FA/B12/B6 supplementation were not effective in improving cognition within one year . The walking programme , however , was efficacious in improving memory in men and memory and attention in women with better adherence . Trial registration : International St and ard R and omised Controlled Trial Number Register , 19227688 , http://www.controlled-trials.com/is rct The hippocampus shrinks in late adulthood , leading to impaired memory and increased risk for dementia . Hippocampal and medial temporal lobe volumes are larger in higher-fit adults , and physical activity training increases hippocampal perfusion , but the extent to which aerobic exercise training can modify hippocampal volume in late adulthood remains unknown . Here we show , in a r and omized controlled trial with 120 older adults , that aerobic exercise training increases the size of the anterior hippocampus , leading to improvements in spatial memory . Exercise training increased hippocampal volume by 2 % , effectively reversing age-related loss in volume by 1 to 2 y. We also demonstrate that increased hippocampal volume is associated with greater serum levels of BDNF , a mediator of neurogenesis in the dentate gyrus . Hippocampal volume declined in the control group , but higher preintervention fitness partially attenuated the decline , suggesting that fitness protects against volume loss . Cau date nucleus and thalamus volumes were unaffected by the intervention . These theoretically important findings indicate that aerobic exercise training is effective at reversing hippocampal volume loss in late adulthood , which is accompanied by improved memory function OBJECTIVE the aim of this study was to compare the effects of a functional tasks exercise programme to a cognitive training programme in older adults with mild cognitive impairment . DESIGN a single-blind r and omised control trial with the intervention group compared with an active control group . SETTING out-patient clinic . PARTICIPANTS older adults with mild cognitive impairment ( n = 83 ) aged 60 and older living in the community . METHODS participants were r and omised to either a functional task exercise group ( n = 43 ) or an active cognitive training group ( n = 40 ) for 10 weeks . All outcome measures were undertaken at baseline , post-intervention and 6-month follow-up using Neurobehavioral Cognitive Status Examination , Trail Making Test , Chinese Version Verbal Learning Test , Category Verbal Learning Test , Lawton Instrumental Activities of Daily Living Scale and Problems in Everyday Living Test . RESULTS the functional task exercise group showed significant between-group differences in general cognitive functions , memory , executive function , functional status and everyday problem solving ability . The improvements were sustained over time at 6-month follow-up . CONCLUSION a functional tasks exercise programme is feasible for improving cognitive functions and functional status of older adults with mild cognitive impairment . This may serve as a cost-effective adjunct to the existing interventions for population s with mild cognitive impairment . TRIAL REGISTRATION NUMBER ACTRN12610001025022 Impaired glucose regulation is a defining characteristic of type 2 diabetes mellitus ( T2DM ) pathology and has been linked to increased risk of cognitive impairment and dementia . Although the benefits of aerobic exercise for physical health are well-documented , exercise effects on cognition have not been examined for older adults with poor glucose regulation associated with prediabetes and early T2DM . Using a r and omized controlled design , twenty-eight adults ( 57 - 83 y old ) meeting 2-h tolerance test criteria for glucose intolerance completed 6 months of aerobic exercise or stretching , which served as the control . The primary cognitive outcomes included measures of executive function ( Trails B , Task Switching , Stroop , Self-ordered Pointing Test , and Verbal Fluency ) . Other outcomes included memory performance ( Story Recall , List Learning ) , measures of cardiorespiratory fitness obtained via maximal- grade d exercise treadmill test , glucose disposal during hyperinsulinemic-euglycemic clamp , body fat , and fasting plasma levels of insulin , cortisol , brain-derived neurotrophic factor , insulin-like growth factor-1 , amyloid-β ( Aβ40 and Aβ42 ) . Six months of aerobic exercise improved executive function ( MANCOVA , p=0.04 ) , cardiorespiratory fitness ( MANOVA , p=0.03 ) , and insulin sensitivity ( p=0.05 ) . Across all subjects , 6-month changes in cardiorespiratory fitness and insulin sensitivity were positively correlated ( p=0.01 ) . For Aβ42 , plasma levels tended to decrease for the aerobic group relative to controls ( p=0.07 ) . The results of our study using rigorous controlled methodology suggest a cognition-enhancing effect of aerobic exercise for older glucose intolerant adults . Although replication in a larger sample is needed , our findings potentially have important therapeutic implication s for a growing number of adults at increased risk of cognitive decline OBJECTIVES To apply diagnostic criteria for mild cognitive impairment ( M \n Output:\n " }, { "from": "agent", "value": "Results indicated that physical exercise may benefit cognitive function among older adults who have MCI , including improvements in global cognition , executive function , memory , attention , and processing speed .\nPhysical exercise may also positively impact the physiology of the aging brain ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Objective —To assess whether adding a fibrate to statin therapy reduces residual cardiovascular risk associated with elevated triglycerides and low high-density lipoprotein cholesterol , The Evaluation of Choline Fenofibrate ( ABT-335 ) on Carotid Intima-Media Thickness ( cIMT ) in Subjects with Type IIb Dyslipidemia with Residual Risk in Addition to Atorvastatin Therapy ( FIRST ) trial evaluated the effects of fenofibric acid ( FA ) treatment on cIMT in patients with mixed dyslipidemia on atorvastatin . Approach and Results —This multicenter , double-blind , placebo-controlled study was performed in patients with mixed dyslipidemia ( fasting triglycerides , ≥150 mg/dL ; high-density lipoprotein cholesterol , ⩽45 [ men ] or 55 mg/dL [ women ] ; low-density lipoprotein cholesterol , ⩽100 mg/dL once and averaging ⩽105 mg/dL ) and a history of coronary heart disease or risk equivalent . Patients on background atorvastatin ( continued on starting dose or titrated to 40 mg , if needed ) were r and omized to FA 135 mg or placebo . The primary end point was rate of change from baseline through week 104 of the mean posterior-wall cIMT , measured by ultrasound . In patients with controlled low-density lipoprotein cholesterol while on atorvastatin background therapy , rate of change in posterior-wall cIMT was similar with FA plus atorvastatin ( −0.006 mm/y ) versus atorvastatin monotherapy ( 0.000 mm/y ; P=0.22 ) . FA plus atorvastatin was favored ( P<0.05 ) in 5 of 24 prespecified subgroups : age ≥60 years , history of coronary artery disease , cIMT > 0.795 mm , triglycerides 170 to 235 mg/dL , and statin use at entry . Adverse events were consistent with the known safety profiles of both drugs ; however , FA plus atorvastatin was associated with a greater incidence of renal-related adverse events compared with atorvastatin monotherapy ( 6.5 % versus 0.9 % ) . Conclusions —Compared with atorvastatin monotherapy , FA plus atorvastatin did not further decrease cIMT progression in high-risk patients with mixed dyslipidemia BACKGROUND AND AIMS To assess the efficacy and safety of K-877 ( Pemafibrate ) , a novel selective peroxisome proliferator-activated receptor α modulator ( SPPARMα ) that possesses unique PPARα activity and selectivity , compared with placebo and fenofibrate in dyslipidaemic patients with high triglyceride ( TG ) and low high-density lipoprotein cholesterol ( HDL-C ) levels . METHODS AND RESULTS This study was a double blind , placebo-controlled , parallel-group 12-week clinical trial . The study r and omized 224 patients to K-877 0.025 , 0.05 , 0.1 , 0.2 mg BID , fenofibrate 100 mg QD , or placebo ( 1:1:1:1:1:1 ) groups . Least squares mean percent changes from the baseline TG levels were -30.9 % , -36.4 % , -42.6 % , -42.7 % for the K-877 0.025 , 0.05 , 0.1 , 0.2 mg BID respectively ( p < 0.001 ) , which were greater than that of the fenofibrate 100 mg QD ( -29.7 % , p < 0.001 ) group . Statistically significant improvements from the baseline HDL-C , very-low-density lipoprotein cholesterol , chylomicron cholesterol , remnant lipoprotein cholesterol , apolipoprotein ( apo ) B ( apoB ) , and apoC-III were also observed in the K-877 groups . The incidence of adverse events ( AEs ) in the K-877 groups ( 32.4 - 56.8 % ) was comparable to those in placebo ( 47.2 % ) and fenofibrate 100 mg QD ( 56.8 % ) ; adverse drug reactions ( ADRs ) in the K-877 groups ( 2.7 - 5.4 % ) were less than those in placebo ( 8.3 % ) and fenofibrate 100 mg QD ( 10.8 % ) groups . CONCLUSION In dyslipidaemic patients with high TG and low HDL-C , K-877 improved TG , HDL-C , and other lipid parameters without increasing AEs or ADRs , compared to placebo and fenofibrate . K-877 can be expected to improve atherogenicity and to be a new beneficial treatment for dyslipidaemic patients BACKGROUND AND AIMS Substantial residual cardiovascular risks remain despite intensive statin treatment . Residual risks with high triglyceride and low high-density lipoprotein cholesterol are not the primary targets of statins . K-877 ( pemafibrate ) demonstrated robust efficacy on triglycerides and high-density lipoprotein cholesterol and a good safety profile as a monotherapy . The aim of these studies was to evaluate the efficacy and safety of K-877 add-on therapy to treat residual hypertriglyceridaemia during statin treatment . METHODS The objectives were investigated in two , multicentre , r and omised , double-blind , placebo-controlled , parallel group comparison clinical trials : ( A ) K-877 0.1 , 0.2 , and 0.4 mg/day in combination with pitavastatin for 12 weeks in 188 patients , ( B ) K-877 0.2 ( fixed dose ) and 0.2 ( 0.4 ) ( conditional up-titration ) mg/day in combination with any statin for 24 weeks in 423 patients . RESULTS In both studies , we found a robust reduction in fasting triglyceride levels by approximately 50 % in all combination therapy groups , which was significant compared to the statin-monotherapy ( placebo ) groups ( p < 0.001 ) . High-performance liquid chromatography analysis for lipoprotein subfractions revealed that atherogenic lipoprotein profiles were ameliorated by K-877 add-on therapy , i.e. small low-density lipoproteins decreased whereas larger ones increased , and larger high-density lipoproteins decreased whereas smaller ones increased . The incidence rates of adverse events and adverse drug reactions in K-877 combination therapy groups were comparable to those in statin-monotherapy groups without any noteworthy event in both studies . CONCLUSIONS These results strongly support the favourable benefit-to-risk ratio of K-877 add-on therapy in combination with statin treatment Abstract Aims / Introduction Pemafibrate is a novel selective peroxisome proliferator‐activated receptor‐α modulator with potent triglyceride‐lowering and high‐density lipoprotein cholesterol‐raising effects . We showed that pemafibrate decreased the homeostatic model assessment for insulin resistance in patients with dyslipidemia . To investigate how pemafibrate improves insulin sensitivity , we used a hyperinsulinemic‐euglycemic clamp technique to determine the splanchnic and peripheral glucose uptake in patients with hypertriglyceridemia and insulin resistance . Material s and Methods A total of 27 patients with hypertriglyceridemia and insulin resistance were r and omly assigned to receive pemafibrate ( 0.4 mg/day , b.i.d . ) or placebo treatment for 12 weeks . The hyperinsulinemic‐euglycemic clamp test combined with oral glucose loading was carried out at weeks 0 and 12 to evaluate the splanchnic and peripheral glucose uptake . Results Pemafibrate , but not the placebo , significantly increased the splanchnic glucose uptake rate from baseline ( 19.6 ± 5.9 % with P = 0.005 and 2.1 ± 7.4 % with P = 0.78 , respectively ) , although no significant difference between the groups was observed ( P = 0.084 ) . Conversely , peripheral glucose uptake rate was not significantly altered . Pemafibrate , compared with the placebo , significantly decreased plasma triglycerides ( −61.4 ± 16.4 % vs −2.5 ± 41.4 % , P = 0.001 ) , free fatty acids ( −24.8 ± 23.2 % vs 2.0 ± 26.8 % , P = 0.016 ) and gamma‐glutamyl transpeptidase ( −30 ± 46 vs 10 ± 19 U/L , P = 0.009 ) levels , and significantly increased fibroblast growth factor 21 ( 457.7 ± 402.1 vs −41.7 ± 37.4 pg/mL , P = 0.007 ) levels . Conclusions Pemafibrate increased splanchnic glucose uptake from baseline in patients with hypertriglyceridemia OBJECTIVE The development of new insulin sensitizers is an unmet need for the treatment of type 2 diabetes . We investigated the effect of GFT505 , a dual peroxisome proliferator – activated receptor (PPAR)-α/δ agonist , on peripheral and hepatic insulin sensitivity . RESEARCH DESIGN AND METHODS Twenty-two abdominally obese insulin-resistant males ( homeostasis model assessment of insulin resistance > 3 ) were r and omly assigned in a r and omized crossover study to subsequent 8-week treatment periods with GFT505 ( 80 mg/day ) or placebo , followed by a two-step hyperinsulinemic-euglycemic insulin clamp with a glucose tracer to calculate endogenous glucose production ( EGP ) . The primary end point was the improvement in glucose infusion rate ( GIR ) . Gene expression analysis was performed on skeletal muscle biopsy specimens . RESULTS GFT505 improved peripheral insulin sensitivity , with a 21 % ( P = 0.048 ) increase of the GIR at the second insulin infusion period . GFT505 also enhanced hepatic insulin sensitivity , with a 44 % ( P = 0.006 ) increase of insulin suppression of EGP at the first insulin infusion period . Insulin-suppressed plasma free fatty acid concentrations were significantly reduced on GFT505 treatment ( 0.21 ± 0.07 vs. 0.27 ± 0.11 mmol/L ; P = 0.006 ) . Neither PPARα nor PPARδ target genes were induced in skeletal muscle , suggesting a liver-targeted action of GFT505 . GFT505 significantly reduced fasting plasma triglycerides ( −21 % ; P = 0.003 ) and LDL cholesterol ( −13 % ; P = 0.0006 ) , as well as liver enzyme concentrations ( γ-glutamyltranspeptidase : −30.4 % , P = 0.003 ; alanine aminotransferase : −20.5 % , P = 0.004 ) . There was no safety concern or any indication of PPARγ activation with GFT505 . CONCLUSIONS The dual PPARα/δ agonist GFT505 is a liver-targeted insulin-sensitizer that is a promising drug c and i date for the treatment of type 2 diabetes and nonalcoholic fatty liver disease UNLABELLED Nonalcoholic fatty liver disease ( NAFLD ) covers a spectrum of liver damage ranging from simple steatosis to nonalcoholic steatohepatitis ( NASH ) , fibrosis , and cirrhosis . To date , no pharmacological treatment is approved for NAFLD/NASH . Here , we report on pre clinical and clinical data with GFT505 , a novel dual peroxisome proliferator-activated receptor alpha/delta ( PPAR-α/δ ) agonist . In the rat , GFT505 concentrated in the liver with limited extrahepatic exposure and underwent extensive enterohepatic cycling . The efficacy of GFT505 was assessed in animal models of NAFLD/NASH and liver fibrosis ( Western diet [WD]-fed human apolipoprotein E2 [ hApoE2 ] transgenic mice , methionine- and choline-deficient diet-fed db/db mice , and CCl4 -induced fibrosis in rats ) . GFT505 demonstrated liver-protective effects on steatosis , inflammation , and fibrosis . In addition , GFT505 improved liver dysfunction markers , decreased hepatic lipid accumulation , and inhibited proinflammatory ( interleukin-1 beta , tumor necrosis factor alpha , and F4/80 ) and profibrotic ( transforming growth factor beta , tissue inhib \n Output:\n " }, { "from": "agent", "value": "Conclusions The lipid profile significantly improved in the pemafibrate group than in the placebo group .\nIn addition to the pemafibrate group having an improved lipid profile , which was comparable with that of the fenofibrate group , the AEs were significantly lower than in the fenofibrate group and an improvement in hepatobiliary enzyme activity was also recognized ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Critical thinking ( CT ) is important to nursing education and practice . Although there is evidence that active learning approaches , such as problem-based learning ( PBL ) , are effective in developing CT dispositions , the findings are inconclusive . This study examines the effect of PBL on the development of CT dispositions in nursing students using a crossover-experimental study in a course offered to nursing students in China . All students were r and omly assigned to two parallel groups , with one group receiving PBL and the other receiving lecture-based learning ( LBL ) as a control . The CT Dispositions Inventory-Chinese Version was administered before and after the semester-long course . Data were collected at three time points . No significant differences between groups were noted in overall and sub-scale scores at baseline ; however , pronounced differences in overall posttest scores existed between the PBL and LBL groups . Thus , PBL learning significantly enhanced the CT dispositions of nursing students enrolled in Medical-Surgical Nursing II The project purpose was to determine whether measures of critical thinking show differences between three groups ( simulator , non-simulator , control ) of baccalaureate nursing students . The second purpose was to determine the moderating effect of students ' preferred learning style . All groups experienced a moderate to large effect size in critical thinking scores . The corrected model for the total scale gain score was statistically significant but not significant for learning style or group Critical thinking is essential for professional nursing practice . Promoting critical thinking with teaching strategies has been a focus of nursing education and nursing research . Reading and writing assignments are teaching strategies for fostering critical thinking ability . We developed a course with the emphasis on critical reading and writing . The purpose s of this study were to explore the effect of the course and teaching strategies on promoting critical thinking and to underst and the learning experience and perception of nursing students as part of the course assessment plan . Quasi-experimental design and purposive sampling were used . 170 students of a two-year nursing program were grouped into an experimental and a control group depending on whether or not they took the course . The change in critical thinking ability was evaluated and determined based on performance in an article critique test before and after the course . Data was collected with an assessment tool developed for the purpose s of the research and was analyzed with descriptive statistics , paired t-test , and two-factor analysis of variance with repeated measures and content analysis . The findings were : ( 1 ) The scores on the critique test at the end of the course in both groups were significantly higher than before the course ( p<.001 ) . The improvement in score of the experimental group , however , was significantly higher than that of the control group ( p<.001 ) . ( 2 ) Changes in thinking pattern and learning attitude , as well as a feeling of growth and achievement , were found in content analysis of students ' self-evaluation of their learning experience and perception . Critical thinking skills were applied while learning the course . The results not only provide evidence to support the positive effect of reading and writing assignments on critical thinking ability but also confirm the teaching and learning activity design for the course The purpose of this project was to examine the effect of Narrative Pedagogy in nursing education on students ' ability to move toward cognitive and ethical maturity and thereby increase their autonomy in nursing practice . Students taking a class using Narrative Pedagogy demonstrated \" entry \" and \" exit \" mean scores that showed marginal and statistically significant ( p < 0.05 ) improvement on the Measure of Intellectual Development and the California Critical Thinking Disposition Inventory . Using nonparametric and parametric analyses of variance , there was minor improvement on both scales in cognitive and ethical maturity and the disposition to think critically in the intervention group . For all variables , there were no significant differences between the control group and the intervention group , with or without adjustment for age , the only significant covariate . The cognitive and ethical growth documented by either instrument is probably not large enough to be considered practically significant in terms of movement toward autonomous practice BACKGROUND Educational approaches are thought to have facilitative or hindering effects on students ' critical thinking development . The aim of this study was to compare the effects of problem-based learning ( PBL ) and lecturing approaches on the development of students ' critical thinking . METHODS All 79 Year 1 undergraduate nursing students at a university in Hong Kong were r and omly assigned to 1 of 2 parallel courses delivered by either PBL ( n = 40 ) or lecturing ( n = 39 ) over 1 academic year . The primary outcome measure was students ' critical thinking disposition as measured by the California Critical Thinking Disposition Inventory ( CCTDI ) . Individual interviews were also conducted to elicit the students ' perceptions of their learning experience . Data were collected at 4 timepoints spanning 3 years . RESULTS The overall CCTDI and subscale scores for the PBL group were not significantly different from those of the lecture group at the first timepoint ( pretest ) . Compared with lecture students , PBL students showed significantly greater improvement in overall CCTDI ( P = 0.0048 ) , Truthseeking ( P = 0.0008 ) , Analyticity ( P = 0.0368 ) and Critical Thinking Self-confidence ( P = 0.0342 ) subscale scores from the first to the second timepoints ; in overall CCTDI ( P = 0.0083 ) , Truthseeking ( P = 0.0090 ) and Analyticity ( P = 0.0354 ) subscale scores from the first to the third timepoints ; and in Truthseeking ( P = 0.0173 ) and Systematic ity ( P = 0.0440 ) subscale scores from the first to the fourth timepoints . CONCLUSIONS There were significant differences in the development of students ' critical thinking dispositions between those who undertook the PBL and lecture courses , respectively \n Output:\n " }, { "from": "agent", "value": "The continued use of generalised CT tools is unlikely to help identify appropriate teaching methods that will improve CT abilities of midwifery and nursing students and prepare them for practise ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Background In COPD , functional status is improved by pulmonary rehabilitation ( PR ) but requires specific facilities . Tai Chi , which combines psychological treatment and physical exercise and requires no special equipment , is widely practice d in China and is becoming increasingly popular in the rest of the world . We hypothesized that Tai Chi is equivalent ( ie , difference less than ±4 St. George ’s Respiratory Question naire [ SGRQ ] points ) to PR . Methods A total of 120 patients ( mean FEV1 , 1.11 ± 0.42 L ; 43.6 % predicted ) bronchodilator‐naive patients were studied . Two weeks after starting indacaterol 150 & mgr;g once daily , they r and omly received either st and ard PR thrice weekly or group Tai Chi five times weekly , for 12 weeks . The primary end point was change in SGRQ prior to and following the exercise intervention ; measurements were also made 12 weeks after the end of the intervention . Results The between‐group difference for SGRQ at the end of the exercise interventions was –0.48 ( 95 % CI PR vs Tai Chi , –3.6 to 2.6 ; P = .76 ) , excluding a difference exceeding the minimal clinical ly important difference . Twelve weeks later , the between‐group difference for SGRQ was 4.5 ( 95 % CI , 1.9 to 7.0 ; P < .001 ) , favoring Tai Chi . Similar trends were observed for 6‐min walk distance ; no change in FEV1 was observed . Conclusions Tai Chi is equivalent to PR for improving SGRQ in COPD . Twelve weeks after exercise cessation , a clinical ly significant difference in SGRQ emerged favoring Tai Chi . Tai Chi is an appropriate substitute for PR . Trial Registry Clinical Trials.gov ; No. : NCT02665130 ; URL : www . clinical trials.gov BACKGROUND Although the benefits of exercise on the health of patients with chronic obstructive pulmonary disease ( COPD ) have been widely reported , the effect of Tai Chi as an alternative exercise has not been thoroughly evaluated in patients with COPD . This study reported a r and omised controlled trial , which investigated the effects of Tai Chi on lung function , exercise capacity , and diaphragm strength in patients with COPD . TRIAL DESIGN Single blind r and omised controlled study . SETTING Department of Respiratory Medicine , Xiangya Hospital , Central South University . METHODS Forty patients with COPD were r and omised into either a control group or Tai Chi intervention group . Participants in the control group received only routine care , while participants in the Tai Chi group received routine care and completed a six-month Tai Chi exercise program . OUTCOMES Lung function parameters , blood gas parameters , 6-min walking distance ( 6MWD ) , and diaphragm strength parameters . RESULTS Lung function parameters ( FEV1 : 1.43 ± 0.08 and FEV1 ( % ) predicted : 47.6 ± 4.76 ) , 6MWD ( 476 ± 15 ) and diaphragm strength parameters ( TwPes : 1.17 ± 0.07 , TwPga : -1.12 ± 0.06 , and TwPdi : 1.81 ± 0.09 ) were found to be significantly increased in participants who successfully completed the six-month Tai Chi program compared to participants in the control group who only received routine care ( p<0.05 ) . These parameters were also found to be significantly increased in participants who completed the Tai Chi exercise program compared to the baseline ( p<0.05 ) . In contrast , no significant differences in PaO2 and PaCO2 were observed in participants before or after completing a Tai Chi program or between Tai Chi group and control group ( p>0.05 ) . CONCLUSIONS Tai Chi enhances lung function , exercise capacity , and diaphragm strength . However , this is only preliminary research data and a larger trial is needed for more detailed results OBJECTIVE To determine the feasibility of a r and omized controlled trial of the effect of a tai chi program on quality of life and exercise capacity in patients with COPD . METHODS We r and omized 10 patients with moderate to severe COPD to 12 weeks of tai chi plus usual care ( n = 5 ) or usual care alone ( n = 5 ) . The tai chi training consisted of a 1-hour class , twice weekly , that emphasized gentle movement , relaxation , meditation , and breathing techniques . Exploratory outcomes included disease-specific symptoms and quality -of-life , exercise capacity , pulmonary function tests , mood , and self-efficacy . We also conducted qualitative interviews to capture patient narratives regarding their experience with tai chi . RESULTS The patients were willing to be r and omized . Among 4 of the 5 patients in the intervention group , adherence to the study protocol was excellent . The cohort 's baseline mean ± SD age , percent-of-predicted FEV₁ , and ratio of FEV₁ to forced vital capacity were 66 ± 6 y , 50 ± 12 % , and 0.63 ± 0.14 , respectively . At 12 weeks there was significant improvement in Chronic Respiratory Question naire score among the tai chi participants ( 1.4 ± 1.1 ) , compared to the usual-care group ( -0.1 ± 0.4 ) ( P = .03 ) . There were nonsignificant trends toward improvement in 6-min walk distance ( 55 ± 47 vs -13 ± 64 m , P = .09 ) , Center for Epidemiologic Studies Depression Scale ( -9.0 ± 9.1 vs -2.8 ± 4.3 , P = .20 ) , and University of California , San Diego Shortness of Breath score ( -7.8 ± 3.5 vs -1.2 ± 11 , P = .40 ) . There were no significant changes in either group 's peak oxygen uptake . CONCLUSIONS A r and omized controlled trial of tai chi is feasible in patients with moderate to severe COPD . Tai chi exercise as an adjunct to st and ard care warrants further investigation BACKGROUND Persons with chronic obstructive pulmonary disease ( COPD ) have reduced exercise capacity and levels of physical activity . Supervised , facility-based pulmonary rehabilitation programs improve exercise capacity and reduce dyspnea , but novel long-term strategies are needed to maintain the benefits gained . Mind-body modalities such as Tai Chi which combine aerobic activity , coordination of breathing , and cognitive techniques that alleviate the physical inactivity , dyspnea , and anxiety and depression that are the hallmarks of COPD are promising strategies . METHODS / DESIGN We have design ed a r and omized controlled study to examine whether Tai Chi will maintain exercise capacity in persons with COPD who have recently completed a supervised pulmonary rehabilitation program , compared to st and ard care . The primary outcome is 6-min walk test distance at 6 months . Secondary outcomes include health-related quality of life , dyspnea , mood , occurrence of acute exacerbations , engagement in physical activity , exercise self-efficacy , and exercise adherence . Simultaneously , we are conducting a pilot study of group walking . We will enroll 90 persons who will be r and omized to one of three arms in a 2:2:1 ratio : Tai Chi , st and ard care , or group-based walking . DISCUSSION The Long-term Exercise After Pulmonary Rehabilitation ( LEAP ) study is a novel and clinical ly relevant trial . We will enroll a well-characterized cohort of persons with COPD and will comprehensively assess physiological and psychosocial outcomes . Results of this study will provide the evidence base for persons with COPD to engage in Tai Chi as a low-cost , long-term modality to sustain physical activity in persons who have completed a st and ard short-term pulmonary rehabilitation program . TRIAL REGISTRATION This trial is registered in Clinical Trials.gov , with the ID number of NCT01998724 Objectives . To evaluate the sustaining effects of Tai Chi Qigong ( TCQ ) in improving the psychosocial health in chronic obstructive pulmonary disease ( COPD ) patients in the sixth month . Background . COPD affects both physical and emotional aspects of life . Measures to minimize patients ' suffering need to be implemented . Methods . 206 COPD patients were r and omly assigned into three groups : TCQ group , exercise group , and control group . The TCQ group completed a three-month TCQ program , the exercise group practice d breathing and walking exercise , and the control group received usual care . Results . Significant group-by-time interactions in quality of life ( QOL ) using St. George 's respiratory question naire ( P = 0.002 ) and the perceived social support from friends using multidimensional scale of perceived social support ( P = 0.04 ) were noted . Improvements were observed in the TCQ group only . Conclusions . TCQ has sustaining effects in improving psychosocial health ; it is also a useful and appropriate exercise for COPD patients The aims of the study were to determine the effect of short-form Sun-style t’ai chi ( SSTC ) ( part A ) and investigate exercise intensity of SSTC ( part B ) in people with chronic obstructive pulmonary disease ( COPD ) . Part A : after confirmation of eligibility , participants were r and omly allocated to either the t’ai chi group or control group ( usual medical care ) . Participants in the t’ai chi group trained twice weekly for 12 weeks . Part B : participants who had completed training in the t’ai chi group performed a peak exercise test ( incremental shuttle walk test ) and SSTC while oxygen consumption ( VO2 ) was measured . Exercise intensity of SSTC was determined by the per cent of VO2 reserve . Of 42 participants ( mean±sd forced expiratory volume in 1 s 59±16 % predicted ) , 38 completed part A and 15 completed part B. Compared to control , SSTC significantly increased endurance shuttle walk time ( mean difference 384 s , 95 % CI 186–510 ) ; reduced medial-lateral body sway in semi-t and em st and ( mean difference -12.4 mm , 95 % CI -21– -3 ) ; and increased total score on the chronic respiratory disease question naire ( mean difference 11 points , 95 % CI 4–18 ) . The exercise intensity of SSTC was 53±18 % of VO2 reserve . SSTC was an effective training modality in people with COPD achieving a moderate exercise intensity which meets the training recommendations Introduction Although pulmonary rehabilitation ( PR ) is associated with significant clinical benefits in chronic obstructive pulmonary disease ( COPD ) and has been recommended by guidelines , PR with conventional exercise training has not been widely applied in the clinic because of its inherent limitations . Alternative exercise such as Tai Chi has been investigated and the results are promising . However , the strengths and weaknesses of the exercise modality of Tai Chi , conventional PR and a combination of Tai Chi and conventional PR and the possible mechanisms underlying Tai Chi exercise remain unclear . This study aims to address the above research gaps in a well- design ed clinical trial . Methods and analysis This study is a single-blind , r and omised controlled trial . Participants with stable COPD will be recruited and r and omly assigned to one of four groups receiving Tai Chi exercise , conventional PR using a total body recumbent stepper ( TBRS ) , combined Tai Chi and TBRS , or usual care ( control ) in a 1:1:1:1 ratio . Participants will perform 30 min of supervised exercise three times a week for 8 weeks ; they will receive sequential follow-ups until 12 months after recruitment . The primary outcome will be health-related quality of life as measured by the St George 's Respiratory Question naire . Secondary outcomes will include 6 min walking distance , pulmonary function , the modified Medical Research Council Dyspnoea Scale , the COPD Assessment Test , the Hospital Anxiety and Depression Scale , the Berg Balance Scale , exacerbation frequency during the study period , and systemic inflammatory and immune markers . Ethics and dissemination Ethics approval has been granted by the Clinical Trial and Biomedical Ethics Committee of West China Hospital of Sichuan University ( No TCM-2015 - 82 ) . Written informed consent will be obtained from each participant before any procedures are performed . The study findings will be published in peer- review ed journals and presented at national and international conferences . Trial registration number ChiCTR-IOR-15006874 ; Pre- results OBJECTIVES To evaluate the sustaining effects of Tai chi Qigong in improving the physiological health for COPD patients at sixth month . DESIGN A r and omized controlled trial . Subjects were in three r and omly assigned groups : Tai chi Qigong group , exercise group , and control group . SETTING The 206 subjects were recruited from five general outpatient clinics . INTERVENTIONS Tai chi Qigong group completed a 3-month Tai chi Qigong program . Exercise group practice d breathing and walking as an exercise . Control group received usual care . MAIN OUTCOME MEASURES Primary outcomes included six-minute walking distance and lung functions . Secondary outcomes were dyspnea and fatigue levels , number of exacerbations and hospital admissions . RESULTS Tai chi Qigong group showed a steady improvement in exercise capacity ( P<.001 ) from baseline to the sixth month . The mean walking distance increased from 298 to 349 meters ( + 17 % ) . No significant changes were noted in the other two groups . Tai chi Qigong group also showed improvement in lung functions ( P<.001 ) . Mean forced expiratory volume in 1s increased from .89 to .99l ( + 11 % ) . No significant change was noted in the exercise group . Deterioration was found in the control group , with mean volume decreased from .89 to .84l ( -5.67 % ) . Sign \n Output:\n " }, { "from": "agent", "value": "Conclusions Tai Chi may represent an appropriate alternative or complement to st and ard rehabilitation programs ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: BACKGROUND AND PURPOSE Glyceryl trinitrate ( GTN ) induces delayed migraine attacks in migraine patients . The purpose of this study was to investigate whether pre-treatment with prednisolon could decrease this effect of GTN . METHODS In this double-blind , r and omized and placebo-controlled , crossover study 15 migraineurs with migraine without aura were pre-treated with 150 mg of prednisolone or placebo followed by a 20-min infusion of GTN ( 0.5 ug/kg/min ) . One hour after the GTN-infusion , the participants were sent home , but continued to rate headache and possible associated symptoms by filling out a headache diary every hour for 12 h. There were two equal primary efficacy end-points : frequency of delayed migraine and intensity of delayed headache . RESULTS Nine patients experienced a GTN headache fulfilling the diagnostic criteria for migraine without aura on the placebo day compared with four patients on the prednisolone day ( P = 0.14 ) . Prednisolone pre-treatment did not alter the summed or peak immediate headache responses to GTN significantly ( P = 0.08 , P = 0.07 ) , whereas the peak headache scores during the following 12 h were significantly lower after prednisolone pre-treatment ( median peak score = 1 , range 0 - 8 ) compared with placebo ( median = 4 , range 0 - 8 ) ( P < 0.01 ) . There was no difference between the two treatment days in the effect of GTN on blood flow velocity of the middle cerebral artery ( a decrease ) or on the dilation of the superficial temporal artery or the radial artery . CONCLUSION Pre-treatment with prednisolone did not reduce the immediate GTN-induced headache , did not inhibit the frequency of delayed headache but significantly decreased the intensity of delayed GTN-induced headache . These findings suggest that GTN causes induction of inflammatory mediators , and that this is the mechanism of delayed GTN-induced migraine . They also support a role of inflammatory mediators in spontaneous migraine attacks OBJECTIVE To determine whether the addition of intravenous dexamethasone to st and ard emergency department ( ED ) migraine therapy would decrease the incidence of severe recurrent headache 24 to 48 hours after initial treatment . METHODS Patients aged 19 to 65 years whose headache was severe enough to require parenteral therapy and who met International Headache Society migraine criteria were eligible for this r and omized , double-blind trial . The study was conducted in the ED of 2 community hospitals , 1 of which was a tertiary referral centre . Exclusion criteria included pregnancy , focal findings , fever , meningismus , allergy to the study drug , active peptic ulcer disease and diabetes mellitus . Demographic and clinical data , including headache severity , were recorded . After abortive therapy ( antiemetics , intravenous nonsteroidal agents , dihydroergotamine or opioids ) , blinded nurses administered dexamethasone ( 24 mg intravenously ) or placebo . Patients recorded headache severity on a Visual Analogue Scale ( VAS ) at time T = 0 , T = 30 minutes and T = 60 minutes and at discharge . They were contacted 48 to 72 hours later and asked whether they had suffered a recurrence of their headache , categorized as class A ( severe , provoking another physician visit ) , class B ( severe , interfering with daily activity but not provoking a physician visit ) , class C ( mild , requiring self-medication but not limiting activity ) or class D ( mild , requiring no treatment ) . RESULTS Two of 100 patients were lost to follow-up , leaving 98 in the study sample . Placebo recipients were more likely to be female ; other baseline characteristics were similar between groups . Median VAS pain score was 83 mm on ED arrival , 35 mm after initial treatment and 12 mm on discharge . At follow-up , 65 of 98 patients had suffered headache recurrence . In the placebo versus dexamethasone groups , respectively , the results were 11 versus 0 in class A , 11 versus 9 in class B , 7 versus 11 in class C and 4 versus 12 in class D. Regarding the primary outcome , 9 of 49 dexamethasone patients ( 18 % ) and 22 of 49 placebo patients ( 45 % ) had severe ( classes A and B ) recurrent headache ( odds ratio 0.28 ; 95 % CI , 0.11 to 0.69 ; p = 0 .005 ) . CONCLUSIONS Migraine recurrence is common after \" successful \" ED treatment . Inflammation may be a critical factor in migraine genesis . Intravenous dexamethasone decreases the incidence of severe recurrent headache after ED treatment and should be offered to patients thought to be at risk of recurrent headache Chronic migraine ( CM ) patients frequently overuse symptomatic medications ( SM ) . These medications may create a cycle of rebound , worsening of headache and withdrawal symptoms that perpetuate the headache itself . In addition , the overuse of such substances is believed to counteract the efficacy of preventive treatments . We conducted a prospect i ve r and omized open-label trial comparing approaches to out-patient management in 150 CM patients ( 125 women , 25 men ; ages 18 - 80 years , mean 40.3 ± 13.8 ) with overuse of SM . In each group , 50 patients received education and orientation and were then abruptly withdrawn from all SM . Immediately following withdrawal , the first group took prednisone ( 60 mg/day 2 days , 40 mg/day 2 days and 20 mg/day 2 days ) for 6 days , the second group did not have any regular medications to take and the third group took naratriptan ( 2.5 mg twice a day ) during this initial period . All patients had similar profiles of headache characteristics and consumption ( quality and quantity ) of SM before initiation of the treatment , but most were not severe headache sufferers , heavy SM overusers or were overusing opioids . After 5 weeks the headache frequency and intensity , the prevalence and frequency of withdrawal symptoms and consumption of rescue medications during the first 6 days were compared between groups . In addition , adherence to treatment ( who returned or not and for which reasons , between groups ) and headache frequency , week by week , among the groups of patients were also compared . Forty-four ( 88 % ) patients from the prednisone group , 41 ( 82 % ) from the ‘ nothing ’ group and 35 ( 70 % ) from the naratriptan group adhered to the treatment and returned . The were no differences between groups with regard to treatment adherence ( P = 0.072 ) , headache frequency as well as intensity ( P = 0.311 ) and decreasing of days with headache after 5 weeks and weekly ( P = 0.275 ) . However , the incidence of withdrawal symptoms and consumption of rescue drugs was higher among the patients who did not take regular medications during the first 6 days ( P = 0.0001 and P = 0.006 ) . We concluded that CM patients with moderate overuse of SM other than opioids may be detoxified on an out-patient basis regardless of the strategy adopted with regard to the use of regular drugs during the initial days of withdrawal , but prednisone and naratriptan may be useful for reducing withdrawal symptoms and rescue medication consumption . Further controlled studies are necessary to confirm these observations Background : Intravenous Valproate ( IVVP ) has been used in the treatment of migraine in some studies ; however , it is far better known in the management of status epilepticus . Methods : Consecutive patients with migraine in our Headache Clinic were enrolled in this prospect i ve , r and omized clinical trial in 2011 . The patients were r and omized into two therapeutic groups , one receiving 900 mg IVVP ( Orifil ) and the other 16 mg IV Dexamethasone ( IVDEX ) diluted in 150 CC normal saline and infused for 10 minutes . Worst severity of pain before treatment and least severity at 3 hours after the infusion using a 0 - 10 point numeric rating scale were recorded . An interview with the patient was performed 72 hours after treatment to detect a possible relapse of headache . Results : Thirty-one migraine status patients , comprising 28 women and 3 men at a mean±SD age of 33.355±12.373 SD , were investigated . Differences in the therapeutic effects of IVVP ( Orifil ) and IVDEX on pain score were not significant between the two groups ( t=0.933 , df=29 ; P=0.358 ) . Relapse of headache occurred in 68.42 % of the IVVP ( Orifil ) group and 66.67 % of the IVDEX group . Distribution of relapse was not significantly different between the two therapeutic groups of patients ( P=0.870 ) . Conclusion : IVVP ( Orifil ) was similar in efficacy to IVDEX as abortive therapy in patients with migraine status . IVVP ( Orifil ) appears to offer a safe and well-tolerated abortive treatment . Trial Registration Number : I RCT Purpose To investigate the efficacy of prednisone for treatment of withdrawal headache in patients with medication overuse headache ( MOH ) . Patients and methods In this prospect i ve double-blind , placebo-controlled , parallel design ed multicentre trial , 96 consecutive patients with MOH were r and omized to withdrawal treatment with either 100 mg prednisone or placebo over 5 days . Patients were enrolled if they met the International Headache Society criteria for MOH and were diagnosed with migraine or episodic tension-type headache as primary headache . Exclusion criteria comprised significant neurological or psychiatric disorders . Withdrawal symptoms , including headache severity and intake of rescue medication , were documented for 14 days after r and omization . Results Patients treated with prednisone did not experience fewer hours of moderate or severe headache than patients receiving placebo . However , patients requested less rescue medication within the first 5 days . Conclusions During withdrawal in MOH , prednisone reduces rescue medication without decreasing the severity and duration of withdrawal headache Background There are many drugs recommended for pain relief in patients with migraine headache . Methods In a prospect i ve double blind r and omized clinical trial , 90 patients ( age ≥ 18 ) presenting to Emergency medicine Department with Migraine headache were enrolled in two equal groups . We used intravenous propofol ( 10 mg every 5–10 minutes to a maximum of 80 mg , slowly ) and intravenous dexamethasone ( 0.15 mg/kg to a maximum of 16 mg , slowly ) , in group I and II , respectively . Pain explained by patients , based on VAS ( Visual Analogue Scale ) was recorded at the time of entrance to ED , and after injection . Data were analyzed by paired sample s t test , using SPSS 16 . P < 0.05 was considered to be statistically significant . Results The mean of reported pain ( VAS ) was 8 ± 1.52 in propofol group and 8.11 ± 1.31 in dexamethasone group at presenting time ( P > 0.05 ) . The VAS in propofol group was obviously decreased to 3.08 ± 1.7 , 1.87 ± 1.28 and 1.44 ± 1.63 after 10 , 20 and 30 minutes of drug injection , respectively . The VAS in dexamethasone group was 5.13 ± 1.47 , 3.73 ± 1.81 and 3.06 ± 2 after 10 , 20 and 30 minutes of drug injection , respectively . The mean of reported VAS in propofol group was less than dexamethasone group at the above mentioned times ( P < 0.05 ) . The reduction of headache in propofol group , also , was very faster than dexamethasone group ( P < 0.05 ) . There were no adverse side effects due to administration of both drugs . Conclusions Intravenous propofol is an efficacious and safe treatment for patients presenting with Migraine headache to the emergency department . Trial registration Clinical Trials I RCT OBJECTIVE To evaluate whether the addition of intravenous ( i.v . ) dexamethasone to st and ard emergency department ( ED ) benign headache therapy would reduce the incidence of headache recurrence at 48 - 72 hours . METHODS This r and omized , double-blind , placebo-controlled clinical trial of adult patients presenting with the chief complaint of headache was conducted in the ED of 2 academic , urban Level 1 hospitals . Headache evaluation and therapy were determined by the treating physician , and , before discharge , patients were administered either 10 mg of IV dexamethasone or placebo . The treatment groups had similar baseline characteristics , abortive therapy , IV fluids and degree of pain relief achieved before discharge . Patients were contacted 48 - 72 hours following discharge and asked whether their headache was \" better , \" \" worse \" or \" remained unchanged \" when compared with their symptoms at discharge . Those whose headaches were \" worse \" or \" unchanged , \" and those who reported a return of headache after being pain free at discharge were considered to be treatment failures and classified as having had a recurrence . The patient 's headache at follow-up was further categorized as severe ( i.e. , provoking another physician visit or interfering with daily activity ) or mild ( i.e. , requiring self-medication or no treatment ) . RESULTS Fifty-seven patients met the inclusion criteria and 2 were lost to follow-up , leaving 5 \n Output:\n " }, { "from": "agent", "value": "All meta-analyses revealed efficacy of adjuvant corticosteroids to various abortive medications — indicating generalizability .\nAdverse effects were tolerable .\nHigher disability , status migrainosus , incomplete pain relief , and previous history of headache recurrence predicted outcome favorability .\nConclusions Our literature review suggests that with corticosteroid treatment , recurrent headaches become milder than pretreated headaches and later respond to nonsteroidal therapy .\nSingle-dose intravenous dexamethasone is a reasonable option for managing resistant , severe , or prolonged migraine attacks" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: OBJECTIVE The aim of this study was to compare perinatal outcomes of patients with second-trimester ultrasonographic evidence of preterm dilatation of the internal os treated with cerclage versus those of patients not treated with cerclage . STUDY DESIGN From May 1998 through June 1999 patients with ultrasonographic evidence of preterm dilatation of the internal os between 16 and 24 weeks ' gestation were r and omly assigned to receive a McDonald cerclage or no cerclage . Before r and om assignment all patients underwent amniocentesis and urogenital cultures and then received 48 hours of therapy with indomethacin and antibiotics . After treatment each patient was followed up as an outpatient with bed rest and weekly ultrasonographic evaluation . RESULTS Of the 61 patients 31 were r and omly assigned to cerclage and 30 were r and omly assigned to no cerclage . There were no differences between groups with respect to maternal demographic characteristics , risk factors for preterm birth , cervical measurements , rescue procedures , readmission , chorioamnionitis , and abruptio placentae . The mean gestational age at delivery ( 33.5 + /- 6.3 weeks ) and the perinatal death rate ( 12 . 9 % ) in the cerclage group were similar to the mean gestational age at delivery ( 34.7 + /- 4.7 weeks ; P = .4 ) and the perinatal death rate ( 10.0 % ; P = .9 ) in the no-cerclage group . CONCLUSION Treatment with McDonald cerclage of preterm dilatation of the cervix detected ultrasonographically during the second trimester did not improve perinatal outcomes OBJECTIVE Our purpose was to compare the accuracy of ultrasonographic and manual cervical examinations for the prediction of preterm delivery . STUDY DESIGN One hundred two singleton pregnancies at high risk for preterm delivery were followed up prospect ively from 14 to 30 weeks with both serial cervical ultrasonography measurements and manual examinations of the length of the cervix . The primary outcome studied was preterm ( < 35 weeks ) delivery . RESULTS Excluding six induced preterm deliveries , 96 pregnancies were analyzed . The mean cervical length measured by ultrasonography was 20.6 mm in pregnancies delivered preterm ( n = 17 ) and 31.3 mm in pregnancies delivered at term ( n = 79 ) ( p = 0.003 ) ; the mean cervical lengths measured by manual examination were 16.1 mm and 18.6 mm in the same preterm and term pregnancies , respectively ( not significant ) . The sixteenth- and twentieth-week ultrasonographic cervical lengths predicted preterm delivery most accurately ( p < 0.0005 ) . The 25th percentiles of ultrasonographic ( 25 mm ) and manual ( 16 mm ) cervical lengths showed relative risks for preterm delivery of 4.8 ( 95 % confidence interval 2.1 to 11.1 , p = 0.0004 ) and 2.0 ( 95 % confidence interval 0.5 to 4.7 , p = 0.1 ) , respectively ; sensitivity , specificity , and positive and negative predictive values were 59 % , 85 % , 45 % , 91 % , and 41 % , 77 % , 28 % , and 86 % , respectively . CONCLUSION Cervical length measured by ultrasonography is a better predictor of preterm delivery than is cervical length measured by manual examination . Cervical ultrasonography in patients at high risk for preterm birth seems to be most predictive of preterm delivery when it is performed between 14 and 22 weeks ' gestation OBJECTIVE To compare cervical length measurements obtained at 11 to 14 weeks and 22 to 24 weeks of gestation in an unselected group of pregnant women and to correlate the measurements with time of delivery . METHODS This was a prospect i ve study involving 529 pregnant women attending for routine antenatal care who underwent transvaginal scans at 11 - 14 weeks and 22 - 24 weeks for evaluation of cervical length . The mean cervical length was calculated at both stages of gestation and lengths were compared between groups which delivered at term or prematurely , this being defined as delivery before 37 completed weeks of gestation . RESULTS The mean cervical lengths at 11 - 14 and 22 - 24 weeks were , respectively , 42.4 mm and 38.6 mm . Cervical length at 11 - 14 weeks was not significantly different between the groups which delivered at term ( 42.7 mm ) and preterm ( 40.6 mm ) . However , at the 22 - 24-week evaluation , cervical length was significantly shorter in the group which had a preterm delivery than in that which had a term delivery ( 26.7 mm and 39.3 mm , respectively ; P = 0.0001 ) . In the group of women with a previous history of one or more preterm deliveries , there was a greater shortening in cervical length from the first to the second evaluation than there was in the group of women with no previous history of preterm delivery . This shortening was also more pronounced in the group which delivered prematurely ( from 40.6 mm to 26.7 mm ) than in that which delivered at term ( from 42.7 mm to 39.3 mm ) . CONCLUSION There is a spontaneous shortening in the pregnant cervix from the first to the second trimester of pregnancy . The shortening is more rapid in pregnant women who deliver prematurely and who have a history of previous preterm delivery BACKGROUND Measurement of mid-gestation cervix length has become a common screening tool for preterm birth . Our study was design ed to assess the value of cervix length and serum relaxin in the prediction of spontaneous preterm birth at < 35 and < 37 weeks ' gestation in a general obstetric population . METHODS A prospect i ve cohort of women with a singleton pregnancy had blood collected at 24 and 28 weeks ' gestation for determination of serum relaxin immediately before transvaginal ultrasound measurement of cervical length . Patients and referring physicians were blinded to cervix length and relaxin levels to preclude changes in management . The primary outcomes were spontaneous delivery at < 35 and < 37 weeks ' gestation . RESULTS A total of 1004 women entered the study . Delivery data were not available for 20 women who delivered elsewhere . Twenty women were excluded because preterm delivery was undertaken because of pregnancy abnormalities . Of the 964 women with known gestational age at delivery , 46 ( 4.8 % ) delivered at < 37 weeks and 16 ( 1.7 % ) at < 35 weeks ' gestation . Mean cervix length at 28 weeks ( 36.7 + /- 7.3 mm ) was significantly shorter than at 24 weeks ( 37.8 + /- 7.1 mm ) ( P < 0.001 ) . Cervix length at 24 and 28 weeks ' gestation was equally predictive of preterm birth . A cervix length of < or = 30 mm at 28 weeks had a sensitivity of 57.1 % , a specificity of 81.8 % , and a positive predictive value of 4.5 % for birth at < 35 weeks . Serum relaxin levels were not correlated with cervix length at either 24 or 28 weeks . Serum relaxin at 24 and 28 weeks ' gestation was not associated with preterm birth before or after controlling for patient characteristics and cervix length . CONCLUSION Serum relaxin levels at 24 and 28 weeks ' gestation are not associated with preterm birth . Although cervix length is associated with preterm birth , its positive predictive value is low . Given the lack of proven therapies for those at risk , cervix length does not appear to be a useful screening tool for preterm delivery in the general obstetric population OBJECTIVE To investigate the efficacy of vaginal progesterone to prevent early preterm birth in women with sonographic evidence of a short cervical length in the midtrimester . METHODS This was a planned , but modified , secondary analysis of our multinational , multicenter , r and omized , placebo-controlled trial , in which women were r and omized between 18 + 0 and 22 + 6 weeks of gestation to receive daily treatment with 90 mg of vaginal progesterone gel or placebo . Cervical length was measured with transvaginal ultrasound at enrollment and at 28 weeks of gestation . Treatment continued until either delivery , 37 weeks of gestation or development of preterm rupture of membranes . Maternal and neonatal outcomes were evaluated for the subset of all r and omized women with cervical length < 28 mm at enrollment . The primary outcome was preterm birth at < /= 32 weeks . RESULTS A cervical length < 28 mm was identified in 46 r and omized women : 19 of 313 who received progesterone and 27 of 307 who received the placebo . Baseline characteristics of the two groups were similar . In women with a cervical length < 28 mm , the rate of preterm birth at < /= 32 weeks was significantly lower for those receiving progesterone than it was for those receiving the placebo ( 0 % vs. 29.6 % , P = 0.014 ) . With progesterone , there were fewer admissions into the neonatal intensive care unit ( NICU ; 15.8 % vs. 51.9 % , P = 0.016 ) and shorter NICU stays ( 1.1 vs. 16.5 days , P = 0.013 ) . There was also a trend toward a decreased rate of neonatal respiratory distress syndrome ( 5.3 % vs. 29.6 % , P = 0.060 ) . CONCLUSION Vaginal progesterone may reduce the rate of early preterm birth and improve neonatal outcome in women with a short sonographic cervical length OBJECTIVES To assess the role of cervical sonography and to compare various sonographic cervical parameters in their ability to predict spontaneous preterm birth in high-risk singleton gestations . DESIGN A prospect i ve cohort of 469 high-risk gestations were longitudinally evaluated between 15 and 24 weeks ' gestation on 1265 occasions with transvaginal cervical sonography and transfundal pressure . The cervical parameters obtained were funnel width and length , cervical length , percent funneling and cervical index . The information obtained was used for patient management . Restriction of physical activities was initiated at cervical lengths of < or = 2.5 cm with cerclage as an option for cervical lengths of < or = 2.0 cm . RESULTS Receiver operating characteristic curve analyses showed that a cervical length of < or = 2.5 cm between 15 and 24 weeks ' gestation was equal to the other sonographic cervical parameters in its ability to predict spontaneous preterm birth . The sensitivities for delivery at < 28 , < 30 , < 32 and < 34 weeks ' gestation were 94 % , 91 % , 83 % and 76 % , respectively , while the negative predictive values were 99 % , 99 % , 98 % and 96 % , respectively . The placement of a cerclage did not influence the positive and negative predictive values . In comparison to women with other risk factors , cervical length was best in the prediction of preterm birth in women with a prior mid-trimester loss ; an optimal cut-off of < or = 1.5 cm had sensitivities for delivery at < 28 , < 30 , < 32 and < 34 weeks ' gestation of 100 % , 100 % 92 % and 81 % , respectively . The rate of preterm delivery at < 34 weeks ' gestation increased dramatically when the cervical length was < or = 1.5 cm . Cervical length was the only independent variable that entered the logistic regression model for the prediction of preterm delivery at < 34 weeks ' gestation . CONCLUSIONS In high-risk singleton gestations a cervical length of < or = 2.5 cm was equal to other sonographic cervical parameters in its ability to predict spontaneous preterm birth and was better for the prediction of earlier forms of prematurity ( at < 28 and < 30 weeks ) than later forms ( at < 32 and < 34 weeks ) . The optimal cervical lengths and their performance for predicting prematurity may be influenced by obstetric risk factors In a cohort of 43 women with viable , singleton pregnancies , cervical dilatation greater than 4 cm , and absent labor between 20 and 27 weeks gestation , 22 women who underwent emergency cerclage within six hours of admission , were compared prospect ively with 15 women who elected conservative bed rest treatment . The two groups were demographically similar . Emergency cervical cerclage result ed in a longer mean gestational age at delivery compared to bed rest ( p = 0.001 ) . Women treated with cerclage required a significantly shorter period of antepartum hospitalization ( p = 0.001 ) , required less tocolysis ( p = 0.005 ) , and experienced fewer preterm membrane ruptures compared to women in the bed rest group ( p = 0.01 ) , although the latency period , following preterm rupture of membranes was shorter in the cerclage group ( p = 0.005 ) . There was no statistical difference in the frequencies of chorioamnionitis , maternal morbidity and cesarean section between the two groups . Although the perinatal mortality in the two groups was not significantly different ( p = 0.3 ) , emergency cerclage result ed in a significantly higher mean birth weight compared to conservative bed rest treatment ( p \n Output:\n " }, { "from": "agent", "value": "Use of the ultrasonographic technique review ed in this guideline may help identify women at risk of preterm birth and , in some circumstances , lead to interventions that may reduce the rate of preterm birth ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: OBJECTIVE The aims of the study were to assess factors responsible for the reduction of preoperative anxiety in patients undergoing breast and abdominal surgeries . In particular , we investigated whether question prompt lists ( QPL ) , patients ' knowledge , or the communication skills of surgeons had effects on anxiety reduction . METHODS Patients were r and omly assigned to QPL and control groups . Anxiety was assessed on the State Trait Anxiety Inventory . RESULTS Both groups showed significant reduction in anxiety between initial consultation and one day prior to surgery , with QPL patients showing a trend towards a greater reduction of anxiety after surgery and a significant reduction at the first outpatient follow-up . Satisfaction with consultation and the doctor 's ability to answer questions concerning diagnosis , and treatment were significantly associated with anxiety reduction . CONCLUSION Effective anxiety reduction hinged on doctors ' communication abilities and patients ' satisfaction with the consultation Active participation in the medical consultation has been demonstrated to benefit aspects of patients ’ subsequent psychological well-being . We investigated two interventions promoting patient question -asking behaviour . The first was a question prompt sheet provided before the consultation , which was endorsed and worked through by the clinician . The second was a face to face coaching session exploring the benefits of , and barriers to , question -asking , followed by coaching in question -asking behaviour employing rehearsal techniques . Sixty patients with heterogeneous cancers , seeing two medical oncologists for the first time , were r and omly assigned to one of three groups : two intervention groups and one control group . Sociodemographic variables and anxiety were assessed prior to the intervention which preceded the consultation . The consultations were audiotaped and subsequently analysed for question -asking behaviour . Anxiety was assessed again immediately following the consultation . Question naires to assess patient satisfaction , anxiety and psychological adjustment were sent by mail 2 weeks following the consultation . Presentation and discussion of the prompt sheet significantly increased the total number of questions asked and the number of questions asked regarding tests and treatment . Coaching did not add significantly to the effects of the prompt sheet . Psychological outcomes were not different among the groups . We conclude that a question prompt sheet addressed by the doctor is a simple , inexpensive and effective means of promoting patient question asking in the cancer consultation Patient participation in medical consultations has been demonstrated to benefit their subsequent psychological well being . Question asking is one way in which patients can be active . We investigated 2 means of promoting cancer patient question asking . One was the provision of a question prompt sheet to patients prior to their initial consultation with their oncologist . The second was the active endorsement and systematic review of the question prompt sheet by their oncologist . 318 patients with heterogeneous cancers , seeing one of 5 medical and 4 radiation oncologists for the first time , were r and omised to either receive or not receive a question prompt sheet . Doctors were r and omised to either proactively address or passively respond to the question prompt sheet in the subsequent consultation . Anxiety was assessed prior to the consultation . Consultations were audiotaped and content analysed . Anxiety was assessed again immediately following the consultation . Within the next 10 days patients completed question naires assessing information needs , anxiety and satisfaction and were given a structured telephone interview assessing information recall . Patients provided with a question prompt sheet asked more questions about prognosis compared with controls and oncologists gave significantly more prognostic information to these patients . Provision of the question prompt sheet prolonged consultations and increased patient anxiety ; however , when oncologists specifically addressed the prompt sheet , anxiety levels were significantly reduced , consultation duration was decreased and recall was significantly improved . A patient question prompt sheet , used proactively by the doctor , is a powerful addition to the oncology consultation . © 2001 Cancer Research Campaign Background . This investigation examined factors affecting patient involvement in consultations to decide local treatment for early breast cancer and the effectiveness of two methods of preconsultation education aim ed at increasing patient participation in these discussion This study was conducted to evaluate the feasibility of using a computer intervention to enhance communication between healthcare professionals and women with breast cancer . Additional aims were to measure the extent to which women achieved their preferred decisional roles and satisfaction with the clinical medical appointment . This two-arm r and omized clinical trial design included a convenience sample of 749 women with breast cancer attending 3 urban Canadian outpatient oncology clinics . Most women were older than 50 years and had a high school diploma or greater ( 57 % ) . Women in the control group completed measures of decision preference before their clinic appointments . Women in the intervention group were encouraged to use the information and decision preference profiles generated by the computer program at their clinic appointments . Levels of involvement in decision making and satisfaction were measured after the clinic appointments . Results showed that although the majority of women in both groups did assume their preferred roles in decision making , a significantly higher proportion of women in the intervention group reported playing a more passive role than originally planned . Both groups reported high satisfaction levels . Future research is required to study how this computer intervention could be used by clinicians to provide information and decision support to these women The purpose of this study was to determine the helpfulness of a prompt sheet versus a general information sheet for patient communication with physicians . Sixty women with breast cancer attending their first outpatient consultation with a breast medical oncologist were r and omized to receive either a prompt sheet ( PS ) or a general information ( GI ) sheet regarding breast cancer . Analysis of the results found that helpfulness of the written material was rated higher in the PS group ( 8.5 + /- 2 ) than the GI group ( 6.2 + /- 3.6 ) , P = 0.005 . The mean score of helpfulness in communicating with physicians was 7.9 + /- 2.4 and 5.7 + /- 3.8 , respectively , P = 0.01 . There were no significant differences between the groups in the average total number of questions asked by the patients or average physician or patient speaking time . We conclude that a disease-specific prompt sheet provided before medical encounters may assist in communication between patients and physicians OBJECTIVE The objective of this study was to evaluate the patients ' perception of the usefulness of a question prompt sheet ( QPS ) in facilitating the involvement of advanced cancer patients during consultation . METHODS Advanced cancer patients attending their first consultation after diagnosis were r and omly assigned to the intervention group ( received QPS and a hospital introduction sheet ( HIS ) ) or the control group ( received HIS only ) . Analysis was conducted on an intention-to-treat basis . The primary outcome measure was patient rating of the usefulness of the material ( s ) ( numerical rating scale of 0 - 10 ) . RESULTS Sixty-three advanced cancer patients ( 72.4 % response rate ) were enrolled and analyzed . Nearly three-quarters of patients in both groups read the material ( s ) before consultation . The rated usefulness of the material ( s ) for asking questions of physicians was significantly higher in the intervention group than in controls ( 4.4 ± 3.6 and 2.7 ± 2.8 , respectively ; p = 0.033 ) . The mean score of the usefulness of the material ( s ) for underst and ing the treatment plan tended to be higher in the intervention group than in the controls ( 4.9 ± 3.6 and 3.3 ± 2.8 ; p = 0.051 ) . The mean score of willingness to use the material ( s ) in the future was significantly higher in the intervention group than in the controls ( 5.3 ± 3.8 and 2.8 ± 2.8 ; p = 0.006 ) . There were no significant differences between the groups in the average total number of questions asked by patients ( median , 1.0 ; interquartile range in both groups , 2.0 ) . CONCLUSIONS QPS provided before oncology consultation may be useful for advanced cancer patients , on the other h and , it did not directly promote patient confidence to ask questions A r and omized pre- and post-test control group design was conducted in 12 oncology wards to investigate the effectiveness of an intervention , existing of a communication skills training with web-enabled video feedback and a Question Prompt Sheet ( QPS ) , which aim ed to improve patient education to older cancer patients ( ≥65 years ) . The effects were studied by analyzing question naires and video recordings of patient education sessions preceding chemotherapy with 210 different patients . Patients ' recall of information was the primary outcome of the study . Recall was checked against the actual communication in the video-recordings . Moreover , communication skills were assessed by observing the extent to which nurses implemented 67 communication aspects , categorized in seven dimensions , using the QUOTE(chemo ) . Experimental nurses demonstrated a significant intervention effect on communicating realistic expectations . Within-group improvements were measured in the experimental group for tailored communication , affective communication and interpersonal communication . Although the use of a QPS significantly increased question asking , only limited results were found on older patients ' recall scores . The overall proportion recall of recommendations showed a marginally significant pre-/post-change in proportion recall in favour of the experimental group and there was a significant pre-/post-change in two out of six sub-categories . The results indicate that nurses ' communication skills can be improved by communication skills training . More research is needed to underst and the difficult relationship between patient-provider communication and recall of information PURPOSE To determine whether provision of a question prompt list ( QPL ) influences advanced cancer patients ' /caregivers ' questions and discussion of topics relevant to end-of-life care during consultations with a palliative care ( PC ) physician . PATIENTS AND METHODS This r and omized controlled trial included patients r and omly assigned to st and ard consultation or provision of QPL before consultation , with endorsement of the QPL by the physician during the consultation . Consecutive eligible patients with advanced cancer referred to 15 PC physicians from nine Australian PC services were invited to participate . Consultations were audiotaped , transcribed , and analyzed by blinded coders ; patients completed question naires before , within 24 hours , and 3 weeks after the consultation . RESULTS A total of 174 patients participated ( 92 QPL , 82 control ) . Compared with controls , QPL patients and caregivers asked twice as many questions ( for patients , ratio , 2.3 ; 95 % CI , 1.7 to 3.2 ; P < .0001 ) , and patients discussed 23 % more issues covered by the QPL ( 95 % CI , 11 % to 37 % ; P < .0001 ) . QPL patients asked more prognostic questions ( ratio , 2.3 ; 95 % CI , 1.3 to 4.0 ; P = .004 ) and discussed more prognostic ( ratio , 1.43 ; 95 % CI , 1.1 to 1.8 , P = .003 ) and end-of-life issues ( 30 % v 10 % ; P = .001 ) . Fewer QPL patients had unmet information needs about the future ( 21 = 4.14 ; P = .04 ) , which was the area of greatest unmet information need . QPL consultations ( average , 38 minutes ) were longer ( P = .002 ) than controls ( average , 31 minutes ) . No differences between groups were observed in anxiety or patient/physician satisfaction . CONCLUSION Providing a QPL and physician endorsement of its use assists terminally ill cancer patients and their caregivers to ask questions and promotes discussion about prognosis and end-of-life issues , without creating patient anxiety or impairing satisfaction This study aims to develop and pilot a question prompt sheet to assist esophageal cancer patients to obtain desired information in the consultation in which potentially curative esophagectomy is discussed . Whether a prompt sheet affected patients ' question asking , the number and scope of topics discussed , the length of the consultation , and patients ' satisfaction is investigated . Patients ( n= 30 ) were r and omized either to receive care as usual ( control group ) or to receive a prompt sheet ( intervention group ) . All patients completed a baseline question naire , their consultations were audio-recorded and content-coded , and they received a structured telephone interview 2 days after the consultation to assess satisfaction . Patients provided with the prompt sheet marked a median of 19 questions . They asked significantly more questions as compared with patients in the control group ( median of 12 vs. 8 questions ) . Questions mainly addressed treatment options and procedures . No differences were found with regard to consultation length and patient satisfaction . Our results suggest that providing patients with a simple , easy-to-implement tool such as a question prompt is appreciated and helps patients to ask more questions during the consultation without increasing the length of the consultation OBJECTIVE Does decision navigation ( DN ) increase prostate cancer patients ' confidence and certainty in treatment decisions , while reducing regret associated with the decisions made ? METHODS Two hundred eighty-nine newly diagnosed prostate cancer patients were eligible . 123 consented and were r and omised to usual care ( n = 60 ) or navigation ( n = 63 ) . The intervention involved a ' navigator ' guiding the patient in creating a personal question list for a consultation and providing a CD and typed summary of the consultation to patients , the general practitioner and physician . The primary outcome was decisional self efficacy . Secondary outcomes included decisional conflict ( DCS ) and decisional regret ( RS ) . Measures of mood ( Hospital Anxiety and Depression Scale ) and adjustment ( Mental Adjustment to Cancer Scale ) were included to detect potential adverse effects of the intervention . RESULTS ANOVA showed a main effect for the group ( F = 7.161 , df 1 , p = 0.009 ) . Post hoc comparisons showed significantly higher decisional self efficacy in the navigated patients post-consultation and 6 months later . Decisional conflict was lower for navigated patients initially ( t = 2.005 , df = 105 , p = 0.047 ) , not at follow-up ( t = 1.969 , df = 109 , p = 0.052 ) . Regret scores were significantly lower in the navigation group compared to the controls 6 months later ( t = -2.130 , df = 100 , p = 0.036 ) . There was no impact of the intervention on mood or adjustment . CONCLUSION Compared to control patients , navigated patients were more confident in making decisions about cancer treatment , were more certain they had made the right decision after the consult \n Output:\n " }, { "from": "agent", "value": "The majority of QPL interventions were given to patients before their consultation in hardcopy .\nIt is suggested that characteristics of a QPL intervention ( i.e. , the number of questions on a QPL and provider training ) can influence its effectiveness .\nQuestion Prompt List interventions are effective in improving communication , psychological and cognitive outcomes of cancer patients" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: PURPOSE This study examines the long-term results of a r and omized prospect i ve study comparing primary versus saphenous vein patch ( VP ) closure after carotid endarterectomy ( CEA ) . METHODS One-hundred thirty-six patients undergoing 163 CEAs over a 46-month period were prospect ively r and omized to VP , or primary closure . Patients with internal carotid artery diameters less than 5 mm and those requiring complex CEAs underwent obligatory vein patch ( OVP ) . Patients were monitored with duplex scanning every 3 months for 1 year and every 6 months thereafter . All patients received aspirin . RESULTS There were three perioperative strokes ( one in the primary group , two in the OVP group ) and no perioperative deaths . Two perioperative revisions were performed within 30 days of the original CEA for residual disease . During a mean follow-up of 59 + /- 4 months , nine ipsilateral neurologic events have occurred , including two strokes and seven transient ischemic attacks . Sixteen patients had duplex evidence of recurrent stenosis , and one was associated with a stroke 36 months after CEA . Recurrence rates were similar in all groups ( cumulative recurrence at 5 years : primary 7.8 % , VP 14.3 % , OVP 5.3 % ) . Of the 136 patients ( 163 procedures ) , 72 ( 53 % ) ( 88 procedures ) are alive and well , 16 ( 11.7 % ) ( 19 procedures ) have been lost to follow-up , and 48 patients ( 35.3 % ) ( 56 procedures ) have died . The cumulative stroke-free survival rate at 84 months was 71 % for VP , 74 % for OVP , and 60 % for the primary group . CONCLUSIONS These results demonstrate that CEA is a durable procedure . The use of VP closure did not produce superior long-term results compared with the use of primary closure in this select group of patients PURPOSE This study examines the long-term clinical outcome and the incidence of recurrent stenosis ( > or = 50 % ) after carotid endarterectomy ( CEA ) with primary closure ( PC ) versus vein patch closure ( VPC ) , saphenous ( SVP ) , and jugular vein ( JVP ) and polytetrafluoroethylene patch closure ( PTFE-P ) . METHODS A total of 399 CEAs were r and omized into the following groups : 135 PC , 134 PTFE-P , and 130 VPC ( SVP alternating with JVP ) . Postoperative duplex ultrasound scans were performed at 1 , 6 , and 12 months and every year thereafter . The mean follow-up was 30 months with a range of 1 to 62 months , and demographic characteristics were similar in all groups . Kaplan-Meier analysis was used to estimate the risk of restenosis and the stroke-free survival . RESULTS The incidence of ipsilateral stroke was 5 % ( seven of 135 ) for PC , 1 % ( one of 134 ) for PTFE-P , and 0 % for VPC ( PC vs VPC , p = 0.008 ; PC vs PTFE-P , p = 0.034 ) . Seven strokes occurred in the perioperative period . All three groups had similar mortality rates . The cumulative stroke-free survival rate at 48 months was 82 % for PC , 84 % for PTFE-P , and 88 % for VPC ( p < 0.01 for PC vs PTFE-P or VPC ) . PC had a higher incidence of recurrent stenosis and occlusion ( 34 % ) than PTFE-P ( 2 % ) and VPC ( 9 % ) ( SVP 9 % , JVP 8 % ) ( p < 0.001 ) . PTFE-P had a lower recurrent stenosis rate than VPC ( p < 0.045 ) . Restenoses necessitating a redo CEA were also higher for PC ( 11 % ) than for PTFE-P ( 1 % ) and VPC ( 2 % ) ( p < 0.001 ) . Women with PC had a higher recurrent stenosis rate than men ( 46 % vs 23 % , p = 0.008 ) . Kaplan-Meier analysis showed that freedom from recurrent stenosis at 48 months was 47 % for PC , 84 % for VPC , and 96 % for PTFE-P ( p < 0.001 ) . The SVP and JVP results were comparable . The mean operative diameter of the internal carotid artery was similar in patients with or without restenosis . Significantly more late internal carotid artery dilatations occurred in the VPC group compared with the PC group . CONCLUSIONS Patch closure ( VPC or PTFE-P ) is less likely than PC to cause perioperative stroke . Patching was also superior in lowering the incidence of late recurrent stenoses , especially in women OBJECTIVES Routine patch angioplasty has been advocated following carotid endarterectomy but patching can be associated with complications . This study assesses the effect of a selective patching policy based on distal internal carotid diameter on the rate of restenosis and outcome following carotid endarterectomy . DESIGN , MATERIAL AND METHODS A consecutive series of 213 patients underwent carotid endarterectomy performed by one surgeon . Preoperative carotid dimensions were measured intraoperatively using calipers . Following endarterectomy a 5 mm Dacron patch was selectively employed if the distal internal carotid was 5 mm or less ( group 1 , 95 patients ) or 6 mm or less ( group 2 , 118 patients ) . Patients underwent colour-coded Duplex scanning at 24 h , 1 week , 3 , 6 , 9 , and 12 months , and yearly following this . RESULTS Overall 27 restenoses ( 5 residual ) of 50 % or greater and two occlusions developed . Patching was performed in 47 % of group 1 and 61 % of group 2 arteries . In group 1 14 % of patched compared with 24 % of non-patched arteries developed restenosis at 24 months ( p=0.4 ) . In group 2 13 % of patched compared to 11 % of non-patched arteries developed restenosis at 12 months ( p>0.5 ) . Stroke rate at 24 months were similar for patched and non-patched patients in groups 1 ( p>0.5 ) and 2 ( p=0.4 ) . CONCLUSIONS This study suggests that patch angioplasty of larger carotid arteries may be unnecessary . R and omisation of larger arteries between patch and primary closure would be required to confirm this A prospect i ve study with r and om selection between primary closure and saphenous vein patching after carotid endarterectomy was conducted . Patients were evaluated with intravenous digital subtraction angiography during the initial postoperative period , followed by duplex scanning at 3 and 6 months , and then yearly examinations . The series consisted of 129 carotid endarterectomies , of which 62 were primary closures and 67 were patch procedures . Both groups were identical with regard to risk factors , symptoms , and postoperative control digital subtraction angiography . Restenosis was defined as a stenosis with ≥50 % diameter reduction , as assessed by duplex scanning . Of special interest was the development of restenosis along with the occurrence of cerebrovascular symptoms at long-term follow-up . The follow-up data from the 129 carotid endarterectomies are presented in a life-table analysis . The mean length of follow-up was 5 years ( range 1 to 96 months ) . During the follow-up period 38 patients who had undergone 39 operations died ( mortality rate 30 % ) ; three deaths were attributed to cerebral causes ( two in-hospital deaths due to intracerebral hemorrhage and one cerebral hemorrhage after 6 months ) . Restenosis occurred in 25 cases ( 19 % ) . This restenosis was detected in 5 of 45 men with primary closure ( 11 % ) , 12 of 17 women with primary closure ( 70 % ) , 7 of 49 men with patch closure ( 14 % ) , and 1 of 18 women with patch closure ( 5.5 % ) . The difference between patch and primary closures was found to be statistically significant ( hazard ratio 0.39 ; 95 % confidence interval 0.17 to 0.91;p=0.03 ) . There was no statistical difference in men who had patch and primary closures ( hazard ratio 1.23 ; 95 % confidence interval 0.39 to 3.87;p=0.73 ) , but there was a statistically significant difference in women who had patch and primary closures ( hazard ratio 0.059 ; 95 % confidence interval 0.0076 to 0.45;p=0.007 ) . The hazard ratios in men and women differed significantly ( p=0.014 ) . Late restenoses were seen in all patient groups , patched and nonpatched . Only one patient with an occlusion had cerebrovascular symptoms . In this study recurrence of symptoms within 5 years of follow-up was independent of patching , yet patch closure reduced the risk of recurrent carotid stenosis in women but not in men OBJECTIVE : To define whether or not direct microscopic closure with or without the use of a vascular patch is advantageous in terms of clinical outcome and late vessel occlusion rates after microsurgical carotid endarterectomy . METHODS : Three hundred thirty-eight elective carotid endarterectomies in 315 patients were r and omized to direct arteriotomy or closure with a polyester collagen-coated vascular patch . Ten procedures did not follow the r and omization process because of technical difficulties and were excluded . Vessel patency ( duplex ultrasound ) and outcome were assessed during and immediately after surgery and at 4 and 12 months after surgery . RESULTS : Four-month ultrasound assessment ( n = 321 ) identified five occluded vessels : two in the patch group ( n = 149 ) and three in the direct closure group ( n = 172 ) . Six patients in the patch group had died or were significantly disabled at 4 months , compared with five in the direct closure group . At the 12-month assessment ( n = 313 ) , eight vessels had occluded : five from the patched group ( n = 146 ) and three from the direct closure group ( n = 167 ) . Eight patients in the patch group had died or were significantly disabled , compared with four in the direct closure group . No statistically significant difference between the two groups in terms of vessel occlusion , morbidity , or mortality was seen ( P > 0.1 ) . CONCLUSION : No difference in vessel patency and clinical outcome has been identified after microscopic patch angioplasty and direct arteriotomy repair . The authors conclude that there is no benefit from the routine use of patch angioplasty in microscopic carotid endarterectomy There is much controversy in the literature regarding the precise role of patch angioplasty in carotid endarterectomy . Our report summarizes the theoretical and experimental considerations , including the hemodynamic effects and biologic behavior of the graft , associated with this technique . We present a detailed review of the literature regarding the clinical efficacy of patch angioplasty in carotid endarterectomy , including the early results , the late results , and the incidence and nature of carotid restenosis . We address concerns about the use of patch angioplasty , including the duration of cross-clamping , potential problems with the graft and suture-line disruption , and graft atherogenesis . We conclude that most recent literature indicates that patch angioplasty decreases acute complications ( notably carotid occlusion ) after carotid endarterectomy and prevents or delays carotid restenosis . As pressure increases to achieve a minimal rate of perioperative morbidity , many surgeons are expected to adopt patch angioplasty in more of their cases . However , in the absence of conclusive results from a prospect i ve r and omized study , opinion will continue to be divided regarding the routine versus the selective use of patch grafting in carotid endarterectomy . We present criteria for r and omized trials of this technique INTRODUCTION The use of synthetic patch angioplasty during carotid endarterectomy ( CEA ) has been advocated to reduce restenosis , stroke , and death , but the type of material used is still being debated . This study compared rate of restenosis , neurologic events , and perioperative death in patients undergoing CEA with primary closure versus polyester urethane patch closure . PATIENTS AND METHODS In a prospect i ve r and omized study , we compared patch angioplasty with polyester urethane ( Vascular-patch , B. Braun Medical AG , Tuttlingen , Germany ) to primary closure between February 1999 and March 2002 in 404 operations . Early ( 30-day ) stroke and mortality rate , long-term restenosis , and neurologic events were compared in the two groups during 2.5 to 5 years of follow-up ( median follow-up , 2 years ) . RESULTS Primary closure was used in 216 operations , and patch angioplasty was used in 206 . Clamping time was significantly shorter in the primary closure group ( P < .001 ) . Perioperative mortality and neurologic events were similar in both groups ( 1.9 % vs 3.9 % , P = .21 , odds ratio [ OR ] , 2.1 ; 95 % confidence interval [ CI ] , 0.56 to 9.85 ) . The rate of residual stenosis ( > or = 5 \n Output:\n " }, { "from": "agent", "value": "No significant correlation was found between use of patch angioplasty and the risk of either perioperative or long-term all-cause death rates .\nAUTHORS ' CONCLUSIONS Limited evidence suggests that carotid patch angioplasty may reduce the risk of perioperative arterial occlusion and restenosis .\nIt would appear to reduce the risk of ipsilateral stroke and there is a non significant trend towards a reduction in perioperative any stroke rate and all-cause case fatality" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Summary The present study was partly a clinical pharmacological analysis of the action of imipramine in nocturnal enuresis and partly an attempt to select children who would benefit most from this treatment . 61 fairly severe cases of nocturnal enuresis were studied as out- patients , divided by the criteria primary / secondary enuresis and with/without associated behavioural disturbances . The patients received imipramine , imipramine-N-oxide , emepronium , and a placebo in r and om sequence in a double-blind cross-over trial . There was no difference in effect between placebo and emepronium ; after imipramine the frequency of enuresis fell to 58 % of the figure during placebo treatment , i.e. 31 % of the children became dry ; imipramine-N-oxide reduced the number of wet nights only to 78 % of the number on placebo , 18 % of the children became dry . When the patients were classified into groups imipramine and imipramine-N-oxide were found to have had the greatest effect in cases of presumed psychogenic aetiology , a 65 % reduction of the frequency of wet nights whilst taking the placebo . The most favourable results were in children with combined nocturnal and diurnal enuresis and in those with urinary frequency and imperative urgency . The effect was maintained during treatment for 3 months with the most suitable drug . The dose was 50 mg regardless of the body weight of the patient . There were no serious side effects . It was concluded that the psychopharmacological actions of imipramine and imipramine-N-oxide appear to be important in their effects on enuresis . Imipramine might have been the best drug because success may require the combination of antidepressant and anticholinergic activity . It was not possible to assess in detail its presumed effect on the level of sleep . Thus many children can be treated successfully and the final cure of enuresis may be hastened by breaking a vicious circle of psychological phenomena The study population consisted of 100 children with nocturnal enuresis ( NE ) aged between six and 14 years , who had been r and omly selected amongst the enuretic out patients at the Ankara S.S.K. Children 's Hospital . A placebo-controlled evaluation of piracetam , diphenylhydantoin and psychotherapy was carried out . At the end of the eighth week of the study , it was discovered that the therapeutic effects observed in the patients administered piracetam did not differ from those given the placebo . Therefore , we recommend that psychotherapy in association with a placebo be the first step in the treatment of NE children PURPOSE We prospect ively evaluated the efficacy of a combination of desmopressin and oxybutynin for treating children with nocturnal enuresis , compared to the single drugs imipramine and desmopressin . MATERIAL S AND METHODS We enrolled 158 patients from 2003 to 2004 . Children were r and omly assigned to 1 of 3 groups and treated with desmopressin , imipramine or a combination of desmopressin plus oxybutynin . Of these patients 145 ( 100 boys and 45 girls , mean age 7.8 + /- 2.5 years , range 5 to 15 ) were followed for more than 6 months . Efficacy was measured at 1 , 3 and 6 months in terms of average enuretic frequency , 5-scale response based on change in nocturnal enuretic frequency after treatment and posttreatment enuretic frequency as a percentage of pretreatment baseline frequency . The latter efficacy was classified according to daytime voiding symptoms . Statistical evaluation was performed using chi-square tests and ANOVA . RESULTS Of the 145 children followed 48 received combination therapy , 49 received desmopressin and 48 received imipramine . A total of 68 patients ( 47 % ) had monosymptomatic enuresis and 77 ( 53 % ) had polysymptomatic enuresis . Combination therapy produced the best and most rapid results regardless of whether the children had monosymptomatic or polysymptomatic enuresis . CONCLUSIONS Combination therapy with desmopressin plus oxybutynin for the treatment of pediatric nocturnal enuresis was well tolerated , and gave significantly faster and more cost-effective results than single drug therapy using either desmopressin or imipramine PURPOSE We estimated the spectrum and risk factors for daytime urinary incontinence in school-age children . MATERIAL S AND METHODS A vali date d , reproducible , parent administered daytime incontinence question naire was distributed to r and omly selected school children . The question naire elicited information on demographic factors , prenatal and developmental factors , and bowel and urinary history . The spectrum of daytime urinary incontinence was measured by recording the frequency and amount of incontinence . RESULTS Parents of 2,856 children ( mean age 7.3 years ) completed the question naire . Overall 16.9 % reported any daytime urinary incontinence in the previous 6 months , with 64 % of cases being very mild , 14.8 % mild , 11.6 % moderate and 9.6 % severe . There was low agreement between frequency and amount of incontinence ( weighted kappa 0.03 ) but risk factors were similar . Independent risk factors were nocturnal enuresis ( OR 7.2 , 95 % CI 3.4 to 15.2 ) , female gender ( 5.4 , 2.6 to 11.1 ) , social concerns ( 3.4 , 1.4 to 8.3 ) , urinary tract infection ( 5.6 , 2.0 to 15.6 ) and encopresis ( 3.3 , 1.4 to 7.7 ) . Expressed as population attributable risk , 36 % of moderate to severe daytime incontinence can be attributed to encopresis , nocturnal enuresis , social concerns , female gender or urinary tract infection . Urinary tract infection was a risk factor for boys but not for girls ( interaction p < 0.01 ) . CONCLUSIONS Daytime urinary incontinence in children is a common but heterogeneous disorder . Episodes may be frequent or major or both but appear to share the same causal pathway . Given the risk factors identified , interventions should target endogenous/physiological and environmental factors BACKGROUND Meclofenoxate hydrochloride is a psychostimulant in the nootropic agent group available in capsule and tablet formulations approved for traumatic cataphora , alcoholic poisoning , anoxia neonatorum , and children 's enuresis in China . Although these 2 generic formulations are marketed in China , information regarding their pharmacokinetics and bioequivalence in humans has not been published . OBJECTIVE The aim of this study was to compare the pharmacokinetic properties and bioequivalence of the capsule ( test ) and tablet ( reference ) formulations of meclofenoxate hydrochloride 200 mg in healthy Chinese volunteers . METHODS This single-dose , r and omized-sequence , open-label , 2-period crossover study was performed at the Nanjing First Hospital of Nanjing Medical University , Nanjing , China . Eligible subjects were healthy male volunteers who were r and omly assigned at a 1:1 ratio to receive a single 200-mg dose of the test or reference formulation , followed by a 1-week washout period and administration of the alternate formulation . The study drugs were administered after a 12-hour overnight fast . As a prodrug , meclofenoxate is hydrolyzed into 4-chlorophenoxyacetic acid and is not detected in plasma . The active metabolite of meclofenoxate , chlorophenoxyacetic acid , was assayed using a high-performance liquid chromatography method . For analysis of pharmacokinetic properties , including Cmax , AUC0 - 24 , and AUC0-infinity , blood sample s were obtained at 0.33 , 0.67 , 1 , 1.5 , 2 , 2.5 , 3 , 4 , 6 , 8 , 10 , 14 , and 24 hours after administration . The formulations were considered bioequivalent if the log-transformed ratios of Cmax and AUC were within the predetermined equivalence range ( 80%-125 % ) as established by the US Food and Drug Administration ( FDA ) . Subjects were interviewed concerning the occurrence of adverse events including excitement , insomnia , lassitude , and headache . Tolerability was assessed at baseline ( before administration ) and at 1 , 2 , 6 , and 12 hours after administration by monitoring vital signs and laboratory tests ( hematology , blood biochemistry , hepatic function , and urinalysis ) . RESULTS Twenty-four Chinese male subjects ( mean [range]age,23.5[22 - 30]years;weight,63.3[56 - 68]kg ; height , 171 [ 165 - 184 ] cm ) were enrolled ; all completed the study . No period or sequence effect was observed . The 90 % CIs for the log-transformed ratios of chlorophenoxyacetic acid Cmax , AUC0 - 24 , and AUC0-infinity were 95.7 to 122.9 , 97.6 to 111.9 , and 97.8 to 111.7 , respectively ( all , P>0.05 ) . Similar results were found for the data without log-transformation . No adverse events were reported or observed during this single-dose study . CONCLUSIONS In this small study in healthy Chinese adult male volunteers , a single 200-mg dose of the capsule formulation was found to be bioequivalent to a single 200-mg dose of the tablet formulation based on the US FDA 's regulatory definition ( rate and extent of absorption ) . Both formulations were well tolerated Purpose : The treatment approach for enuresis is controversial due to the lack of consensus as to the exact causes of nocturnal enuresis . Despite various treatment modalities , pharmacotherapy still appears to be the common choice . The aim of this prospect i ve study was the evaluation of the efficacy of combination therapy ( imipramine and oxybutynin ) in patients with enuresis nocturna . Patients and Methods : This prospect i ve study was done with 77 monosymptomatic nocturnal enuretics between July 1996 and December 1998 . Results : Even though there is no statistically significant difference between combination therapy ( imipramine plus oxybutynin ) and monotherapy , clinical data showed that combination therapy is more effective . Conclusions : We conclude that combination of imipramine with oxybutynin is a safe and new choice in the treatment of nocturnal enuresis Various treatment modalities have been used in Primary Nocturnal Enuresis ( PNE ) and pharmacotherapy is widely accepted . Prostagl and ins increase detrusor pressure , decrease urethral pressure and lead to sodium excretion . They also antagonize hydro-osmotic effect of vasopressin by competing with this hormone . According to these functions of prostagl and ins it is suggested that inhibition of prostagl and in synthesis may have value in the management of PNE . We evaluated the efficacy or oral diclofenac sodium treatment in 78 patients . We conclude that diclofenac sodium , an inhibitor of prostagl and in synthesis , is a good alternative agent for nocturnal enuresis particularly as a supplementary treatment combined to Imipramine , with 60 % complete response and 13.3 % recurrence rate PURPOSE This r and omized blinded clinical study was design ed to compare the efficacy of tolterodine treatment combined with behavioral modification , behavioral modification alone and behavioral modification plus placebo in children with nonneurogenic , nonanatomical voiding dysfunction . MATERIAL S AND METHODS A total of 72 children meeting inclusion criteria were r and omly allocated to 1 of 3 groups . One group received tolterodine ( 1 mg twice daily ) along with behavioral modification , 1 received behavioral modification only and 1 received placebo with behavioral modification . A dysfunctional voiding scoring system question naire was completed for all patients at the beginning of the study , and at 1 and 3 months of treatment . RESULTS A total of 71 patients were evaluated . The groups did not differ with respect to age , gender and symptom score before study enrollment ( p > 0.05 ) . Repeated calculations of symptom scores at 1 month of the treatment revealed a significant decrease in symptoms in all 3 groups , with a significant decrease in patients receiving tolterodine . In addition , at month 3 the symptom score of the tolterodine group was significantly lower compared to month 1 , while scores remained steady in the behavioral modification and behavioral modification plus placebo groups . CONCLUSIONS Tolterodine combined with behavioral modification for voiding dysfunction in children without neurological or anatomical abnormality can be recommended as a first line treatment before invasive evaluation This exploratory r and omized , double-blind , double-dummy , placebo-controlled trial of 14 days duration conducted in 22 primary care practice s in the United States was used to compare the efficacy of ibuprofen and pseudoephedrine , administered alone or in combination , to placebo for the treatment of primary nocturnal enuresis ( PNE ) in children aged 6 to 11 years . Ibuprofen ( IBU ) and pseudoephedrine ( PSE ) are not approved for the treatment of PNE . Three hundred eighteen children with PNE were enrolled . Eligible children had ≥ 8 wet nights during a 14-day baseline . Each child was r and omly assigned to 1 of 4 treatment \n Output:\n " }, { "from": "agent", "value": "There was an overall paucity of data regarding outcomes after treatment was withdrawn .\nFor drugs versus placebo , when compared to placebo indomethacin ( risk ratio [ RR ] 0.36 , 95 % CI 0.16 to 0.79 ) , diazepam ( RR 0.22 , 95 % CI 0.11 to 0.46 ) , mestorelone ( RR 0.32 , 95 % CI 0.17 to 0.62 ) and atomoxetine ( RR 0.81 , 95 % CI 0.70 to 0.94 ) appeared to reduce the number of children failing to have 14 consecutive dry nights .\nAlthough indomethacin and diclofenac were better than placebo during treatment , they were not as effective as desmopressin and there was a higher chance of adverse effects .\nThere was an overall paucity of data regarding outcomes after treatment was withdrawn .\nThere was not enough evidence to judge whether or not the included drugs cured bedwetting when used alone .\nThere was limited evidence to suggest that desmopressin , imipramine and enuresis alarms therapy were better than the included drugs to which they were compared .\nIn other review s , desmopressin , tricyclics and alarm interventions have been shown to be effective during treatment ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: INTRODUCTION The aim of this study was to investigate the duration of m and ibular-crowding alleviation with self-ligating brackets compared with conventional appliances and the accompanying dental effects . METHODS Fifty-four subjects were selected from a pool of patients satisfying the following inclusion criteria : non extraction treatment in the m and ibular or maxillary arches ; eruption of all m and ibular teeth ; no spaces in the m and ibular arch ; irregularity index greater than 2 in the m and ibular arch ; and no therapeutic intervention planned with any extraoral or intraoral appliance . The patients were r and omly assigned to 2 groups : 1 group received treatment with a self-ligating bracket ( Damon 2 , Ormco , Glendora , Calif ) and the other with a conventional edgewise appliance ( Microarch , GAC , Central Islip , NY ) , both with 0.022-in slots . The irregularity index of the m and ibular arch was normalized between the groups , and the time to alignment was estimated in days . Treatment duration was assessed by data modeling with the Cox proportional hazard regression . Lateral cephalometric radiographs were used to assess the alteration of m and ibular incisor position before and after alignment . Measurements of intercanine and intermolar widths were also made on dental casts to determine changes associated with correction . RESULTS AND CONCLUSIONS Overall , no difference in the time required to correct m and ibular crowding with Damon 2 and conventional brackets was observed . For moderate crowding ( irregularity index < 5 ) , however , the self-ligating group had 2.7 times faster correction . This difference was marginally insignificant for subjects with irregularity index scores greater than 5 . Greater crowding prolonged treatment by an additional 20 % for each irregularity index unit . Increases in intercanine and intermolar widths associated with crowding correction regardless of bracket group were noted . The self-ligating group showed a statistically greater intermolar width increase than the conventional group . Also , an alignment-induced increase in the proclination of the m and ibular incisors was observed for both bracket groups , but no difference was found between Damon 2 and conventional brackets for this parameter In a clinical trial involving 155 dental arches with irregularity > 5 mm , the rate of alignment was used to compare the alignment efficiency of 16 mil superelastic Ni-Ti versus 17.5 mil triple-str and ed steel archwires , and to determine whether ion implantation of the Ni-Ti wire improved its performance . Subjects were r and omly assigned to archwire types ; both 18 and 22 slot edgewise appliances were employed . Pre-treatment equivalence of the experimental groups was verified . Anterior irregularity was determined monthly ( using Little 's irregularity index ) until it decreased below 2 mm , and the elastomeric ligatures were replaced at each appointment . Effective tooth movement occurred with each of the archwire types . There were no significant differences among wires , but the rate of alignment was significantly faster in the lower arch for subjects with the 22 slot appliance Two arch wires commonly used for initial tooth alignment were compared with regard to their clinical effectiveness . The two arch wires tested were 0.0155-inch diameter multiple-str and ed stainless steel wire ( Dentaflex , Dentaurium , Optident , Yorkshire , Engl and ) and 0.014-inch diameter nickel-titanium alloy wire ( NiTi , ORMCO Co. , Monrovia , Calif. ) . Consecutive patients attending an orthodontic clinic for routine placement of a fixed appliance were r and omly assigned one of these two initial arch wires . Good quality alginate impressions of the appropriate dental arch were taken before arch wire placement and also at the subsequent appointment , which was , on average , 6 weeks later . Seventy-four arches were used in this study . The degree of tooth alignment achieved for each wire type was compared with a Reflex Microscope ( Reflex Measurement Ltd. , Butleigh , Engl and ) to make detailed measurements on the result ant casts . The degree of initial alignment achieved with the two wires was similar over this 6-week period . However , some differences were found for the lower labial segment where the interbracket span is usually reduced and where the superelastic nickel-titanium wire was found to give improved alignment . No threshold of crowding was found where one arch wire performed better than the other Two nickel-titanium archwire types commonly used for initial tooth alignment were compared with regard to the pain/discomfort patients experience during the initial phase of tooth movement . The two archwires used were a superelastic nickel-titanium alloy , 0.014 inch Sentalloy , Light ( GAC International Inc. Central Islip , NY , USA ) and a 0.014 inch Nitinol ( unitek , Monrovia , CA , USA ) , a conventional nickel-titanium aligning archwire . One hundred and twenty-eight consecutive patients attending an orthodontic university clinic and 2 private practice s for routine placement of a fixed appliance were r and omly assigned one of these 2 initial archwires . Assessment s of pain/discomfort were made daily by means of a 100 mm visual analog scale ( VAS ) over the first 7-day period after bonding . On the first day , recordings were made every hour for the first 11 hours . The results showed that the level of discomfort increased continuously every hour after the insertion of either a Sentalloy or a Nitinol as first archwires , with a peak in the first night , remaining high on the second day and decreasing thereafter to baseline level after 7 days . During the first 10 hours it was apparent that the pain/discomfort experienced after placement of a Sentalloy was less than that found with the Nitinol archwire , although a significant difference could be found at 4 hours only . No significant gender-specific differences were found in either archwire group . A significant difference between the upper and lower dental arches was observed during the first 11 hours after placement of either a Sentalloy or a Nitinol archwire , with the lower arch having the higher pain experience . ZusammenfassungZwei verschiedene Bögen aus NiTi-Legierungen , die häufig für die initiale Nivellierung verwendet werden , wurden in Hinsicht auf das Auftreten von Schmerzen/Beschwerden zu Beginn der Zahnbewegung untersucht . Das eine Bogen material war eine superelastische NiTi-legierung , 0,014 inch Sentalloy , Light ( GAC International Inc. , Central Islip , N. Y. ) , das and ere ein herkömmlicher 0,014 inch Nitinol-Bogen ( Unitek , Monrovia , Kalifornien).128 fortlaufend beh and elte Patienten aus einer kieferorthopädischen Universitätsklinik und zwei privaten Praxen , bei denen routinemäßig eine Multib and apparatur eingesetzt werden sollte , wurden r and omisiert für den einen oder den and eren Bogen vorgesehen . Die Beurteilungen der Schmerzen/Beschwerden wurden täglich während der ersten sieben Tage nach dem Einsetzen der festsitzenden Apparatur auf einer visuellen Skala von 100 mm Länge ( visual analogue scale , VAS ) vorgenommen . Zusätzlich wurde am ersten Tag für die ersten elf Stunden nach dem Einsetzen stündlich die Schmerzintensität aufgezeichnet . Die Ergebnisse zeigten , daß die Beschwerden für den ersten Bogen , sowohl für den Sentalloy-als auch für den Nitinol-Bogen , kontinuierlich jede Stunde nach dem Einsetzen anstiegen . Der Höhepunkt wurde in der ersten Nacht erreicht , blieb am zweiten Tag auf derselben Höhe und verringerte sich kontinuierlich bis zum siebten Tag auf das individuelle Ausgangsniveau . Während der ersten zehn Stunden war es offensichtlich , daß nach der Eingliederung der Bögen beim Sentalloy-Bogen deutlich geringere Beschwerden auftraten als bei dem Nitinol-Bogen ; dieser Unterschied war jedoch nur für die ersten vier Stunden signifikant . Keine signifikanten Unterschiede der Beschwerden zwischen den Bogen material ien f and en sich hinsichtlich des Geschlechts der Patienten . Ein signifikanter Unterschied wurde zwischen dem Ober- und dem Unterkiefer während der ersten elf Studen nach dem Einsetzen sowohl des Sentalloy- als auch des Nitinol-Bogens beobachtet ; i m Unterkiefer traten deutlich stärkere Beschwerden auf The aim of this study was to compare three orthodontic archwire sequences . One hundred and fifty-four 10- to 17-year-old patients were treated in three centres and r and omly allocated to one of three groups : A = 0.016-inch nickel titanium ( NiTi ) , 0.018 x 0.025-inch NiTi , and 0.019 x 0.025-inch stainless steel ( SS ) ; B = 0.016-inch NiTi , 0.016-inch SS , 0.020-inch SS , and 0.019 x 0.025-inch SS ; and C = 0.016 x 0.022-inch copper ( Cu ) NiTi , 0.019 x 0.025-inch CuNiTi , and 0.019 x 0.025-inch SS . At each archwire change and for each arch , the patients completed discomfort scores on a seven-point Likert scale at 4 hours , 24 hours , 3 days , and 1 week . Time in days and the number of visits taken to reach a 0.019 x 0.025-inch SS working archwires were calculated . A periapical radiograph of the upper left central incisor was taken at the start of the treatment and after placement of the 0.019 x 0.025-inch SS wire so root resorption could be assessed . There were no statistically significant differences between archwire sequences A , B , or C for patient discomfort ( P > 0.05 ) or root resorption ( P = 0.58 ) . The number of visits required to reach the working archwire was greater for sequence B than for A ( P = 0.012 ) but this could not be explained by the increased number of archwires used in sequence The statistical methodology of health research experiments published in Lancet , the New Engl and Journal of Medicine , and Medical Care between 1975 and 1980 for the presence or absence of an error of experimental design and analysis was examined . The error is the result of inappropriately using patient-related observations as the unit of analysis to form conclusions about provider behavior or outcomes determined jointly by patients and providers . The error was present in 20 of 28 ( 71 % ) health care experiments addressing an issue of health provider professional performance . Its usual effect is to increase erroneously the power of an experiment to detect differences between experimental and control groups . It is likely that this type of error could be avoided by the explicit and prospect i ve definition of hypotheses and the population s to which they are intended to pertain Aim To compare the efficiency of orthodontic archwire sequences produced by three manufacturers . Design Prospect i ve , r and omized clinical trial with three parallel groups . Setting Private orthodontic practice in Caloundra , QLD , Australia Subjects and methods One hundred and thirty‐two consecutive patients were r and omized to one of three archwire sequence groups : ( i ) 3 M Unitek , 0·014 inch Nitinol , 0·017 inch × 0·017 inch heat activated Ni – Ti ; ( ii ) GAC international , 0·014 inch Sentalloy , 0·016 × 0·022 inch Bioforce ; and ( iii ) Ormco corporation , 0·014 inch Damon Copper Ni – Ti , 0·014 × 0·025 inch Damon Copper Ni – Ti . All patients received 0·018 × 0·025 inch slot Victory SeriesTM brackets . Outcome measures M and ibular impressions were taken before the insertion of each archwire . Patients completed discomfort surveys according to a seven‐point Likert Scale at 4 h , 24 h , 3 days and 7 days after the insertion of each archwire . Efficiency was measured by time required to reach the working archwire , m and ibular anterior alignment and level of discomfort . Results No significant differences were found in the reduction of irregularity between the archwire sequences at any time‐point ( T1 : P = 0·12 ; T2 : P = 0·06 ; T3 : P = 0·21 ) or in the time to reach the working archwire ( P = 0·28 ) . No significant differences were found in the overall discomfort scores between the archwire sequences ( 4 h : P = 0·30 ; 24 h : P = 0·18 ; 3 days : P = 0·53 ; 7 days : P = 0·47 ) . When the time‐points were analysed individually , the 3 M Unitek archwire sequence induced significantly less discomfort than GAC and Ormco archwires 24 h after the insertion of the third archwire ( P = 0·02 ) . This could possibly be attributed to the progression in archwire material and archform . Conclusions The archwire sequences were similar in alignment efficiency and overall discomfort . Progression in archwire dimension and archform may contribute to discomfort levels . This study provides clinical justification for three common archwire sequences in 0·018 × 0·025 inch slot brackets OBJECTIVES To examine whether the transition temperature of Cu-NiTi archwires has an effect on the tooth movement during the alignment phase of orthodontic treatment . DESIGN ' Split mouth ' design in r and omly selected patients . SETTING AND SAMPLE POPULATION The Department of Orthodontics , School of Dentistry , University of Aarhus . Fifteen r and omly selected patients with identical level of irregularity in the alignment phase of their treatment . Experiment Variable - Specially manufactured Cu-NiTi archwires for the upper arch were inserted . These consisted of two separate halves , each with its own transition temperature , respectively \n Output:\n " }, { "from": "agent", "value": "There is very weak unreliable evidence , based on one very small study ( n = 24 ) at high risk of bias , that coaxial superelastic NiTi may produce greater tooth movement over 12 weeks , but no information on associated pain or root resorption .\nThere is insufficient evidence to determine whether or not there is a difference between either thermoelastic or CuNiTi and superelastic NiTi initial arch wires .\nAUTHORS ' CONCLUSIONS There is no reliable evidence from the trials included in this review that any specific initial arch wire material is better or worse than another with regard to speed of alignment or pain .\nThere is no evidence at all about the effect of initial arch wire material s on the important adverse effect of root resorption .\nFurther well- design ed and conducted , adequately-powered , RCTs are required to determine whether the performance of initial arch wire material s as demonstrated in the laboratory , makes a clinical ly important difference to the alignment of teeth in the initial stage of orthodontic treatment in patients" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Neuroimaging studies have demonstrated activations in the anterior cingulate cortex ( ACC ) related to the affective component of pain , but not to stimulus intensity . However , it is possible that the low spatial resolution of positron emission tomography , as used in the majority of these studies , obscured areas coding stimulus intensity . We revisited this issue , using a parametric single-trial functional magnetic resonance imaging design , and investigated pain , stimulus intensity , and stimulus awareness ( i.e. , pain unrelated ) responses within the ACC in nine healthy volunteers . Four different stimulus intensities ranging from warm to painful ( 300–600 mJ ) were applied with a thulium yttrium – aluminum granate infrared laser in a r and omized order and rated by the subjects on a five point scale ( P0–P4 ) . Pain-related regions in the ventral posterior ACC showed a response that did not distinguish between innocuous trials ( P0 and P1 ) but showed a positive linear relationship with the blood oxygenation level-dependent contrast signal for painful trials ( P2–P4 ) . Regions in the dorsal anterior ACC along the cingulate sulcus differentiated between P0 ( not perceived ) and P1 but exhibited no additional signal increase with P2 ; these regions are related to stimulus awareness and probably to cognitive processing . Most importantly , we identified a region in the dorsal posterior ACC showing a response that discriminated between nonpainful trials ( P0 and P1 ) ; therefor , this region was simply related to basic sensory processing and not to pain intensity . Stimulus-related activations were all located adjacent to the cingulate motor area , highlighting the strategic link of stimulus processing and response generation in the posterior ACC Background Selective serotonin reuptake inhibitors ( SSRIs ) are popular medications for anxiety and depression , but their effectiveness , particularly in patients with prominent symptoms of loss of motivation and pleasure , has been question ed . There are few studies of the effect of SSRIs on neural reward mechanisms in humans . Methods We studied 45 healthy participants who were r and omly allocated to receive the SSRI citalopram , the noradrenaline reuptake inhibitor reboxetine , or placebo for 7 days in a double-blind , parallel group design . We used functional magnetic resonance imaging to measure the neural response to rewarding ( sight and /or flavor of chocolate ) and aversive stimuli ( sight of moldy strawberries and /or an unpleasant strawberry taste ) on the final day of drug treatment . Results Citalopram reduced activation to the chocolate stimuli in the ventral striatum and the ventral medial/orbitofrontal cortex . In contrast , reboxetine did not suppress ventral striatal activity and in fact increased neural responses within medial orbitofrontal cortex to reward . Citalopram also decreased neural responses to the aversive stimuli conditions in key “ punishment ” areas such as the lateral orbitofrontal cortex . Reboxetine produced a similar , although weaker effect . Conclusions Our findings are the first to show that treatment with SSRIs can diminish the neural processing of both rewarding and aversive stimuli . The ability of SSRIs to decrease neural responses to reward might underlie the question ed efficacy of SSRIs in depressive conditions characterized by decreased motivation and anhedonia and could also account for the experience of emotional blunting described by some patients during SSRI treatment The present study examined whether automaticity , defined here as independence from attentional modulation , is a fundamental principle of the neural systems specialized for processing social signals of environmental threat . Attention was focused on either scenes or faces presented in a single overlapping display . Facial expressions were neutral , fearful , or disgusted . Amygdala responses to facial expressions of fear , a signifier of potential physical attack , were not reduced with reduced attention to faces . In contrast , anterior insular responses to facial expressions of disgust , a signifier of potential physical contamination , were reduced with reduced attention . However , reduced attention enhanced the amygdala response to disgust expressions ; this enhanced amygdala response to disgust correlated with the magnitude of attentional reduction in the anterior insular response to disgust . These results suggest that automaticity is not fundamental to the processing of all facial signals of threat , but is unique to amygdala processing of fear . Furthermore , amygdala processing of fear was not entirely automatic , coming at the expense of specificity of response . Amygdala processing is thus specific to fear only during attended processing , when cortical processing is undiminished , and more broadly tuned to threat during unattended processing , when cortical processing is diminished It is hypothesized that due to an abnormal functioning of the reward system patients with schizophrenia form context -inappropriate associations . It has been shown that the dopamine target regions , especially the ventral striatum , are critical in the formation of reward associations . We wanted to examine how the ventral striatum responds as patients learn reward-related associations and how this neural response is linked to objective and subjective behavioral measures . Functional magnetic resonance imaging ( fMRI ) Blood oxygen level dependent ( BOLD ) responses were examined using aversive Pavlovian learning in 13 medicated patients with schizophrenia and 13 matched healthy controls . Colored circles served as conditioned stimulus ( CS+ ) while a loud , individually adjusted , noise served as the unconditioned stimulus . Circles of another color served as neutral comparators ( CS− ) . Subjective indices were assessed by a post-scan self-report , and galvanic skin responses ( GSR ) were used as objective measures of associative learning . fMRI data were analyzed using a r and om effects model in SPM2 . Patients showed inappropriately strong activations in the ventral striatum in response to the neutral stimulus ( CS− ) as compared to the healthy controls . Consistent with this neural evidence of aberrant learning , patients also showed evidence of abnormal learning by self-report and as indexed by GSR . The main finding here is that patients with schizophrenia , when exposed to neutral stimuli in a threatening situation , show an abnormal pattern of learning . The aberrant activations and response are consistent with the idea that patients aberrantly assign motivational salience to neutral stimuli , and this process may be one of the aberrations that predisposes them to psychosis The experience of pain is subjectively different from the fear and anxiety caused by threats of pain . Functional magnetic resonance imaging in healthy humans was applied to dissociate neural activation patterns associated with acute pain and its anticipation . Expectation of pain activated sites within the medial frontal lobe , insular cortex , and cerebellum distinct from , but close to , locations mediating pain experience itself . Anticipation of pain can in its own right cause mood changes and behavioral adaptations that exacerbate the suffering experienced by chronic pain patients . Selective manipulations of activity at these sites may offer therapeutic possibilities for treating chronic pain Activation studies have shown that in response to evocative visual stimuli , brain activity increases in the visual cortex and limbic areas . However , non-affective characteristics of these images , such as color composition and visual complexity , confound the interpretation of these results . To address this issue , we had subjects rate over 100 images on aversive intensity ( facial mutilation , dead bodies ) and semantic complexity ( number of objects subjects could name ) . From these images , we assembled digitized image sets of non-aversive , mild and strong intensity , balanced on semantic complexity and content ( human faces and figures ) , and adjusted for color composition . A fourth condition consisted of a fixation cross on a blank screen . Thirteen subjects underwent eight positron emission tomography scans using the [ (15)O ] water methodology . Measurement of skin conductance was recorded simultaneously . All picture conditions , relative to the blank screen , activated the amygdalae and bilateral orbitofrontal cortex , while we found activation trends associated with increasing aversive content in the sub-lenticular region . Skin conductance increased during all picture conditions . Relative to the non-aversive pictures , aversive image content caused modulation of occipital and occipital-temporal cortex . These results demonstrated activation of the amygdala to salient , arousing stimuli , and not just aversive stimuli . In addition , they suggest that pictorial complexity , as indexed by our semantic measure , does not account for the modulation of visual cortex by aversive , emotional stimuli Previous functional neuroimaging studies have characterized brain systems mediating associative learning using classical delay conditioning paradigms . In the present study , we used event-related functional magnetic resonance imaging to characterize neuronal responses mediating aversive trace conditioning . During conditioning , neutral auditory tones were paired with an aversive sound [ unconditioned stimulus ( US ) ] . We compared neuronal responses evoked by conditioned ( CS+ ) and nonconditioned ( CS− ) stimuli in which a 50 % pairing of CS+ and the US enabled us to limit our analysis to responses evoked by the CS+ alone . Differential responses ( CS+ vs CS− ) , related to conditioning , were observed in anterior cingulate and anterior insula , regions previously implicated in delay fear conditioning . Differential responses were also observed in the amygdala and hippocampus that were best characterized with a time × stimulus interaction , indicating rapid adaptation of CS+-specific responses in medial temporal lobe . These results are strikingly similar to those obtained with a previous delay conditioning experiment and are in accord with a preferential role for medial temporal lobe structures during the early phase of conditioning . However , an additional activation of anterior hippocampus in the present experiment supports a view that its role in trace conditioning is to maintain a memory trace between the offset of the CS+ and the delayed onset of the US to enable associative learning in trace conditioning Functional neuroimaging studies in humans have shown that nociceptive stimuli elicit activity in a wide network of cortical areas commonly labeled as the \" pain matrix \" and thought to be preferentially involved in the perception of pain . Despite the fact that this \" pain matrix \" has been used extensively to build models of where and how nociception is processed in the human brain , convincing experimental evidence demonstrating that this network is specifically related to nociception is lacking . The aim of the present study was to determine whether there is at least a subset of the \" pain matrix \" that responds uniquely to nociceptive somatosensory stimulation . In a first experiment , we compared the fMRI brain responses elicited by a r and om sequence of brief nociceptive somatosensory , non-nociceptive somatosensory , auditory and visual stimuli , all presented within a similar attentional context . We found that the fMRI responses triggered by nociceptive stimuli can be largely explained by a combination of ( 1 ) multimodal neural activities ( i.e. , activities elicited by all stimuli regardless of sensory modality ) and ( 2 ) somatosensory-specific but not nociceptive-specific neural activities ( i.e. , activities elicited by both nociceptive and non-nociceptive somatosensory stimuli ) . The magnitude of multimodal activities correlated significantly with the perceived saliency of the stimulus . In a second experiment , we compared these multimodal activities to the fMRI responses elicited by auditory stimuli presented using an oddball paradigm . We found that the spatial distribution of the responses elicited by novel non-target and novel target auditory stimuli resembled closely that of the multimodal responses identified in the first experiment . Taken together , these findings suggest that the largest part of the fMRI responses elicited by phasic nociceptive stimuli reflects non nociceptive-specific cognitive processes BACKGROUND Loss aversion in decision-making refers to a higher sensitivity to losses than to gains . Loss aversion is conceived as an affective interference in cognitive processes such as judgment and decision-making . Loss aversion in non-risky choices has not been studied in schizophrenia . METHOD Forty-two individuals with schizophrenia and 42 non-patient control subjects , matched by gender and age , were r and omized to two different scenarios ( a buying scenario and a selling scenario ) . Subjects were asked to evaluate the price of a decorated mug . Schizophrenia subjects were re-tested four weeks later with the other scenario . RESULTS Contrary to non-patient controls , schizophrenia subjects did not show loss aversion . In the schizophrenia group , absence of loss aversion was correlated with age , duration of illness , number of months in State hospitals , and poorer performance in the Wisconsin Card Sorting Test , but not with current psychopathology and two domains of emotional experience . CONCLUSIONS Absence of loss aversion in schizophrenia represents a deficit in the processing of emotional information during decision-making . It can be interpreted as a lack of integration between the emotional and the cognitive systems , or to a more diffuse and de-differentiated impact of emotional information on decision-making . Future studies should bring more clarity to this question Echoplanar functional magnetic resonance imaging ( fMRI ) was used in normal human subjects to investigate the role of the amygdala in conditioned fear acquisition and extinction . A simple discrimination procedure was employed in which activation to a visual cue predicting shock ( CS+ ) was compared with activation to another cue presented alone ( CS- ) . CS+ and CS- trial types were intermixed in a pseudor and om order . Functional images were acquired with an asymmetric spin echo pulse sequence from three coronal slices centered on the amygdala . Activation of the amygdala/periamygdaloid cortex was observed during conditioned fear acquisition and extinction . The extent of activation during acquisition was significantly correlated with autonomic indices of conditioning in individual subjects . Consistent with a recent electrophysiological recording study in the rat ( Quirk et al. , 1997 ) , the profile of the amygdala response was temporally grade d , although this dynamic was only statistically reliable during extinction . These results provide further evidence for the conservation of amygdala function across species and implicate an amygdalar contribution to both acquisition and extinction processes during associative emotional learning tasks Anticipatory anxiety is a complex combination of a future-oriented cognitive state , negative affect , and autonomic arousal . A dual-task paradigm of anticipation of electric shocks and a motor-learning task was used to examine the changes in neural patterns of activation associated with modulation of the cognitive state in anxiety by a distracting motor task \n Output:\n " }, { "from": "agent", "value": "Our results highlighted the recruitment of the anterior cingulate cortex , the anterior insula , and the amygdala as well as other subcortical ( e.g. , thalamus , midbrain ) and cortical ( e.g. , orbitofrontal ) regions in both animals and humans .\nImportantly , involvement of these regions remained independent of sensory modality .\nThis study provides evidence for a core neural network mediating aversion in both animals and humans ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Memory performance by four age groups ( 30 - 45 years , 46 - 60 years , 61 - 75 years , and 76 - 90 years ) was compared on a multi-trial verbal recall task with 20-minute and 1-day delay free recall and recognition trials . The rate of acquisition across 5 learning trials was similar for all ages except the youngest group whose performance was constrained by a ceiling effect . The level of acquisition achieved was less in the two oldest groups . Words gained across trials and words lost across trials made similar contributions to the shape of the learning curve for the acquisition trials . Subjective organization decreased with age , but remained strongly related to the number of words recalled during acquisition for all age groups . The two oldest age groups demonstrated significant declines in words recalled on the 20-minute and 1-day delay trials . A subset of the oldest group demonstrated more rapid forgetting at the 1-day delay when participants from all age conditions were matched on acquisition . Thus , many aspects of free recall were impaired with age , and variance measurement of recall showed greater inter-individual differences with increasing age . This increase in individual differences could reflect a single form of age-related memory impairment , or it could indicate that memory impairment in the elderly is due to multiple processes . The importance of testing across the life span and using tests that examine a variety of memory components and processes for establishing norms and clarifying age-related deficits are discussed This study describes the neural circuitry underlying temporally separated components of working memory ( WM ) performance-stimulus encoding , maintenance of information during a delay , and the response to a probe . While other studies have applied event-related fMRI to separate epochs of WM tasks , this study differs in that it employs a methodology that does not make any a priori assumptions about the shape of the hemodynamic response ( HDR ) . This is important because no one model of the HDR is valid across the range of activated brain regions and stimulus types . Systematic modeling inaccuracies may lead to the misattribution of activity to adjacent events . Twelve healthy subjects performed a numerical version of the Sternberg Item Recognition Paradigm adapted for rapid presentation event-related fMRI . This paradigm emphasized maintenance rather than manipulative WM processes and used a subcapacity WM load . WM trials with different delay lengths were compared to fixation . The HDR of the entire WM trial for each trial type was estimated using a finite impulse response ( FIR ) . Regional activity associated with the Encode , Delay , and Probe epochs was identified using contrasts that were based on the FIR estimates and by examining the HDRs . Each epoch was associated with a distinct but overlapping pattern of regional activity . Activation of the dorsolateral prefrontal cortex , thalamus , and basal ganglia was exclusively associated with the probe . This suggests that frontostriatal neural circuitry participates in selecting an appropriate response based on the contents of WM Estrogen Therapy ( ET ) may protect against age-related cognitive decline and neuropsychiatric disorders ( e.g. Alzheimer 's disease ) . The biological basis for this putative neuroprotective effect is not fully understood , but may include modulation of cholinergic systems . Cholinergic dysfunction has been implicated in age-related memory impairment and Alzheimer 's disease . However , to date no one has investigated the effect of long-term ET on brain cholinergic muscarinic receptor aging , and related this to cognitive function . We used Single Photon Emission Tomography ( SPET ) and (R , R)[(123)I]-I-QNB , a novel lig and with high affinity for m(1)/m(4 ) muscarinic receptors , to examine the effect of long-term ET and age on brain m(1)/m(4 ) receptors in healthy females . We included 10 younger premenopausal subjects and 22 postmenopausal women ; 11 long-term ET users ( all treated following surgical menopause ) and 11 ET never-users ( surgical menopause , n=2 ) . Also , verbal memory and executive function was assessed in all postmenopausal subjects . Compared to young women , postmenopausal women ( ET users and never-users combined ) had significantly lower muscarinic receptor density in all brain regions examined . ET users also had higher muscarinic receptor density than ET never-users in all the brain regions , and this reached statistical significance in left striatum and hippocampus , lateral frontal cortex and thalamus . Moreover , in ET users , (R , R)[(123)I]-I-QNB binding in left hippocampus and temporal cortex was significantly positively correlated with plasma estradiol levels . We also found evidence for improved executive function in ET users as compared to ET never-users . However , there was no significant relationship between receptor binding and cognitive function within any of the groups . In healthy postmenopausal women use of long-term ET is associated with reduced age-related differences in muscarinic receptor binding , and this may be related to serum estradiol levels Estradiol has been shown to interact with the cholinergic system to affect cognition in postmenopausal women . This study further investigated the interaction of estradiol and cholinergic system functioning on verbal memory and attention in two groups of healthy younger ( ages 50 - 62 ) and older ( ages 70 - 81 ) postmenopausal women . Twenty-two postmenopausal women were r and omly and blindly placed on 1 mg of 17-beta estradiol orally for 1 month then 2 mg for 2 months or matching placebo pills after which they participated in three anticholinergic challenge sessions when verbal memory and attention were assessed . Subjects were administered either the antimuscarinic drug scopolamine ( SCOP ) , the antinicotinic drug mecamylamine ( MECA ) , or placebo . After the first challenge phase , they were crossed over to the other hormone treatment for another 3 months and repeated the challenges . Results showed that estradiol pretreatment significantly attenuated the anticholinergic drug-induced impairments on a test of episodic memory ( the Buschke Selective Reminding Task ) for the younger group only , while estradiol treatment impaired performance of the older group . The results suggest that younger subjects may experience more cholinergic benefit from estradiol treatment than older subjects , supporting the concept of a critical period for postmenopausal estrogen use CONTEXT Postmenopausal women have a greater risk than men of developing Alzheimer disease , but studies of the effects of estrogen therapy on Alzheimer disease have been inconsistent . On July 8 , 2002 , the study drugs , estrogen plus progestin , in the Women 's Health Initiative ( WHI ) trial were discontinued because of certain increased health risks in women receiving combined hormone therapy . OBJECTIVE To evaluate the effect of estrogen plus progestin on the incidence of dementia and mild cognitive impairment compared with placebo . DESIGN , SETTING , AND PARTICIPANTS The Women 's Health Initiative Memory Study ( WHIMS ) , a r and omized , double-blind , placebo-controlled clinical trial , began enrolling participants from the Women 's Health Initiative ( WHI ) estrogen plus progestin trial in May 1996 . Of the 4894 eligible participants of the WHI study , 4532 ( 92.6 % ) postmenopausal women free of probable dementia , aged 65 years or older , and recruited from 39 of 40 WHI clinical centers were enrolled in the WHIMS . INTERVENTION Participants received either 1 daily tablet of 0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate ( n = 2229 ) , or a matching placebo ( n = 2303 ) . MAIN OUTCOME MEASURES Incidence of probable dementia ( primary outcome ) and mild cognitive impairment ( secondary outcome ) were identified through a structured clinical assessment . RESULTS The mean ( SD ) time between the date of r and omization into WHI and the last Modified Mini-Mental State Examination ( 3MSE ) for all WHIMS participants was 4.05 ( 1.19 ) years . Overall , 61 women were diagnosed with probable dementia , 40 ( 66 % ) in the estrogen plus progestin group compared with 21 ( 34 % ) in the placebo group . The hazard ratio ( HR ) for probable dementia was 2.05 ( 95 % confidence interval [ CI ] , 1.21 - 3.48 ; 45 vs 22 per 10 000 person-years ; P = .01 ) . This increased risk would result in an additional 23 cases of dementia per 10 000 women per year . Alzheimer disease was the most common classification of dementia in both study groups . Treatment effects on mild cognitive impairment did not differ between groups ( HR , 1.07 ; 95 % CI , 0.74 - 1.55 ; 63 vs 59 cases per 10 000 person-years ; P = .72 ) . CONCLUSIONS Estrogen plus progestin therapy increased the risk for probable dementia in postmenopausal women aged 65 years or older . In addition , estrogen plus progestin therapy did not prevent mild cognitive impairment in these women . These findings , coupled with previously reported WHI data , support the conclusion that the risks of estrogen plus progestin outweigh the benefits UNLABELLED The aim of the double-blind , placebo-controlled study was to investigate the effects of a continuous combined estrogen-progestogen treatment ( Climodien , Lafamme ) as compared with estrogen alone on vigilance in insomniac postmenopausal syndrome patients , objectified by EEG mapping . METHODS In a 3-arm , 2-month parallel group design phase , patients received a combination of estradiol valerate 2 mg and the novel progestogen dienogest 3 mg ( Climodien 2/3 ) or estradiol valerate 2 mg alone or placebo . In a subsequent open-label phase , all patients received estradiol valerate 2 mg+dienogest 2 mg ( Climodien 2/2 ) . EEG mapping was carried out before and after the 2-month double-blind phase as well as after the 2-month open-label treatment . RESULTS As compared with placebo , Climodien 2/3 induced a marked and highly significant increase in absolute power in all frequency b and s , specifically in alpha-2 activity . Moreover , a significant increase in relative alpha-2 power , a decrease in relative delta and beta power as well as an acceleration of the dominant frequency and of the delta and alpha centroids suggested a marked improvement in vigilance . In contrast , under estradiol valerate 2 mg alone , only a slight augmentation of alpha and attenuation of relative delta and beta power occurred , suggesting only a slight vigilance improvement as compared with placebo . Thus , dienogest 2 mg increased the estrogen effect , which was also confirmed by a statistical evaluation of the differences between Climodien 2/3 and estradiol valerate alone ( augmentation of alpha-2 , attenuation of relative beta , acceleration of the dominant frequency ) . Moreover , Climodien 2/2 also markedly increased alpha-2 power , decreased relative beta-2 power and accelerated the alpha centroid . Finally , comparing Climodien 2/3 with Climodien 2/2 , there was even a dose-efficacy relation . CONCLUSIONS Estradiol valerate 2 mg improves vigilance slightly , thereby confirming previous findings . The additional administration of dienogest does not minimize the effect of estrogen , but on the contrary increases it , which makes the combination superior to both placebo and estradiol valerate alone . Vigilance improvement may be of great therapeutic benefit to menopausal syndrome patients at a time when increased adaptability is needed to adjust to increasing sexual , marital , occupational and social difficulties known to occur specifically in this period of life Recent research in rodents suggests that extended and chronic hormone therapy can exacerbate memory impairments and irreversibly damage cells . However , aerobic fitness regimens have been shown to spare brain tissue and cognitive function . In addition , interactions between estrogen treatment and exercise have been reported in rodents . However , whether aerobic fitness and hormone treatments show interactive effects on human brain tissue and cognition has yet to be determined . Here we report two unique and important results : ( a ) HRT treatment up to 10 years in duration spares gray matter in prefrontal cortex and is associated with better performance on measures of executive function , whereas HRT treatment beyond 10 years in duration increases the degree of prefrontal deterioration and amplifies the decline on measures of executive functioning ( b ) higher fitness levels augment the effects of shorter duration s of hormone treatment and ameliorate the declines associated with prolonged hormone treatment In the last ten years , numerous mechanisms by which sex steroids modify cortical function have been described . For example , estrogen replacement improves verbal memory in women , and animal studies have shown effects of estrogen on hippocampal synaptogenesis and function . Little is known about sex steroid effects on other aspects of memory , such as frontal lobe-mediated working memory . We examined the relationships between working memory and sex steroid concentrations and whether sex steroid supplementation would modify age-related loss of working memory in older men and women . Before hormone supplementation , working memory , tested with the Subject Ordered Pointing Test ( SOP ) , was worse in older subjects than younger subjects , and there was no evidence of gender differences at either age . Testosterone supplementation improved working memory in older men , but a similar enhancement of working memory was not found in older women supplemented with estrogen . In men , testosterone and estrogen effects were reciprocalwith better working memory related to a higher testosterone to estrogen ratio . \n Output:\n " }, { "from": "agent", "value": "RESULTS There is some evidence for a beneficial effect of estrogen alone on verbal memory in younger naturally post-menopausal women and more consistent evidence from small-n studies of surgically post-menopausal women .\nThere is stronger evidence of a detrimental effect of conjugated equine estrogen plus medroxyprogesterone acetate on verbal memory in younger and older post-menopausal women .\nObservational studies and pharmacological models of menopause provide initial evidence of improvements in executive function with hormone therapy .\nFuture studies should include measures of executive function and should address pressing clinical questions ; including what formulation of combination hormone therapy is cognitively neutral/beneficial , yet effective in treating hot flashes in the early post-menopause" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Background Recent studies in North American context s have suggested that the Housing First model is a promising strategy for providing effective services to homeless people with mental illness . In the context of the highly generous French national health and social care system , which is easily accessible and does not require out-of-pocket payment , the French Health Ministry insists on rigorous techniques , including r and omized protocol s , to evaluate the impact of Housing First approaches in France . Method and design A prospect i ve r and omized trial was design ed to assess the impact of a Housing First intervention on health outcomes and costs over a period of 24 months on homeless people with severe mental illness , compared to Treatment-As-Usual . The study is being conducted in four cities in France : Lille , Marseille , Paris and Toulouse . The inclusion criteria are as follows : over 18 years of age , absolutely homeless or in precarious housing , and possessing a ‘ high ’ level of need : diagnosis of schizophrenia or bipolar disorder and moderate to severe disability according to the Multnomah Community Ability Scale ( score ≤ 62 ) and at least one of the following three criteria : 1 ) having been hospitalized for mental illness two or more times in any one year during the preceding five years ; 2 ) co-morbid alcohol or substance use ; and 3 ) having been recently arrested or incarcerated . Participants will be r and omized to receiving the Housing First intervention or Treatment-As-Usual . The Housing First intervention provides immediate access to independent housing and community care . The primary outcome criterion is the use of high-cost health services ( that is , , number of hospital admissions and number of emergency department visits ) during the 24-month follow-up period . Secondary outcome measures include health outcomes , social functioning , housing stability and contact with police services . An evaluation of the cost-effectiveness and cost-utility of Housing First will also be conducted . A total of 300 individuals per group will be included . Discussion This is the first study to examine the impact of a Housing First intervention compared to Treatment-As-Usual in France . It should provide key information to policymakers concerning the cost-effectiveness and health outcomes of the Housing First model in the French context .Trial registration The current clinical trial number is BACKGROUND Homelessness is associated with increased risks of mortality but it has not previously been possible to distinguish whether this is typical of other socio-economically deprived population s , the result of a higher prevalence of morbidity or an independent risk of homelessness itself . The aim of this study was to describe mortality among a cohort of homeless adults and adjust for the effects of morbidity and socio-economic deprivation . METHODS Retrospective 5-year study of two fixed cohorts , homeless adults and an age- and sex-matched r and om sample of the local non-homeless population in Greater Glasgow National Health Service Board area for comparison . RESULTS Over 5 years of observation , 1.7 % ( 209/12 451 ) of the general population and 7.2 % ( 457/6323 ) of the homeless cohort died . The hazard ratio of all-cause mortality in homeless compared with non-homeless cohorts was 4.4 ( 95 % CI : 3.8 - 5.2 ) . After adjustment for age , sex and previous hospitalization , homelessness was associated with an all-cause mortality hazard ratio of 1.6 ( 95 % CI : 1.3 - 1.9 ) . Homelessness had differential effects on cause-specific mortality . Among patients who had been hospitalized for drug-related conditions , the homeless cohort experienced a 7-fold increase in risk of death from drugs compared with the general population . CONCLUSIONS Homelessness is an independent risk factor for deaths from specific causes . Preventive programmes might be most effectively targeted at the homeless with these conditions OBJECTIVE Housing First with assertive community treatment ( ACT ) is a promising approach to assist people with serious mental illness to exit homelessness . The article presents two-year findings from a multisite trial on the effectiveness of Housing First with ACT . METHODS The study design was a r and omized controlled trial conducted in five Canadian cities . A sample of 950 participants with serious mental illness who were absolutely homeless or precariously housed were r and omly assigned to receive either Housing First with ACT ( N=469 ) or treatment as usual ( N=481 ) . RESULTS Housing First participants spent more time in stable housing than participants in treatment as usual ( 71 % versus 29 % , adjusted absolute difference [AAD]=42 % , p<.01 ) . Compared with treatment-as-usual participants , Housing First participants who entered housing did so more quickly ( 73 versus 220 days , AAD=146.4 , p<.001 ) , had longer housing tenures at the study end-point ( 281 versus 115 days , AAD=161.8 , p<.01 ) , and rated the quality of their housing more positively ( adjusted st and ardized mean difference [ASMD]=.17 , p<.01 ) . Housing First participants reported higher quality of life ( ASMD=.15 , p<.01 ) and were assessed as having better community functioning ( ASMD=.18 , p<.01 ) over the two-year period . Housing First participants showed significantly greater gains in community functioning and quality of life in the first year ; however , differences between the two groups were attenuated by the end of the second year . CONCLUSIONS Housing First with ACT is an effective approach in various context s for assisting individuals with serious mental illness to rapidly exit homelessness Objective No previous experimental trials have investigated Housing First ( HF ) in both scattered site ( SHF ) and congregate ( CHF ) formats . We hypothesized that CHF and SHF would be associated with a greater percentage of time stably housed as well as superior health and psychosocial outcomes over 24 months compared to treatment as usual ( TAU ) . Methods Inclusion criteria were homelessness , mental illness , and high need for support . Participants were r and omised to SHF , CHF , or TAU . SHF consisted of market rental apartments with support provided by Assertive Community Treatment ( ACT ) . CHF consisted of a single building with supports equivalent to ACT . TAU included existing services and supports . Results Of 800 people screened , 297 were r and omly assigned to CHF ( 107 ) , SHF ( 90 ) , or TAU ( 100 ) . The percentage of time in stable housing over 24 months was 26.3 % in TAU ( reference ; 95 % confidence interval ( CI ) = 20.5 , 32.0 ) , compared to 74.3 % in CHF ( 95 % CI = 69.3 , 79.3 , p<0.001 ) and 74.5 % in SHF ( 95 % CI = 69.2 , 79.7 , p<0.001 ) . Secondary outcomes favoured CHF but not SHF compared to TAU . Conclusion HF in scattered and congregate formats is capable of achieving housing stability among people experiencing major mental illness and chronic homelessness . Only CHF was associated with improvement on select secondary outcomes . Registration Current Controlled Trials : IS RCT N57595077 IMPORTANCE Scattered-site housing with Intensive Case Management ( ICM ) may be an appropriate and less-costly option for homeless adults with mental illness who do not require the treatment intensity of Assertive Community Treatment . OBJECTIVE To examine the effect of scattered-site housing with ICM services on housing stability and generic quality of life among homeless adults with mental illness and moderate support needs for mental health services . DESIGN , SETTING , AND PARTICIPANTS The At Home/Chez Soi project was an unblinded , r and omized trial . From October 2009 to July 2011 , participants ( N = 1198 ) were recruited in 4 Canadian cities ( Vancouver , Winnipeg , Toronto , and Montreal ) , r and omized to the intervention group ( n = 689 ) or usual care group ( n = 509 ) , and followed up for 24 months . INTERVENTIONS The intervention consisted of scattered-site housing ( using rent supplements ) and off-site ICM services . The usual care group had access to existing housing and support services in their communities . MAIN OUTCOMES AND MEASURES The primary outcome was the percentage of days stably housed during the 24-month period following r and omization . The secondary outcome was generic quality of life , assessed by a EuroQoL 5 Dimensions ( EQ-5D ) health question naire . RESULTS During the 24 months after r and omization , the adjusted percentage of days stably housed was higher among the intervention group than the usual care group , although adjusted mean differences varied across sites . [ table : see text ] The mean change in EQ-5D score from baseline to 24 months among the intervention group was not statistically different from the usual care group ( 60.5 [ 95%CI , 58.6 to 62.5 ] at baseline and 67.2 [ 95%CI , 65.2 to 69.1 ] at 24 months for the intervention group vs 62.1 [ 95 % CI , 59.9 to 64.4 ] at baseline and 68.6 [ 95%CI , 66.3 to 71.0 ] at 24 months for the usual care group , difference in mean changes , 0.10 [ 95%CI , −2.92 to 3.13 ] , P=.95 ) . CONCLUSIONS AND RELEVANCE Among homeless adults with mental illness in 4 Canadian cities , scattered site housing with ICM services compared with usual access to existing housing and community services result ed in increased housing stability over 24 months , but did not improve generic quality of life . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N42520374 OBJECTIVES We examined the longitudinal effects of a Housing First program for homeless , mentally ill individuals ' on those individuals ' consumer choice , housing stability , substance use , treatment utilization , and psychiatric symptoms . METHODS Two hundred twenty-five participants were r and omly assigned to receive housing contingent on treatment and sobriety ( control ) or to receive immediate housing without treatment prerequisites ( experimental ) . Interviews were conducted every 6 months for 24 months . RESULTS The experimental group obtained housing earlier , remained stably housed , and reported higher perceived choice . Utilization of substance abuse treatment was significantly higher for the control group , but no differences were found in substance use or psychiatric symptoms . CONCLUSIONS Participants in the Housing First program were able to obtain and maintain independent housing without compromising psychiatric or substance abuse symptoms CONTEXT Homeless adults , especially those with chronic medical illnesses , are frequent users of costly medical services , especially emergency department and hospital services . OBJECTIVE To assess the effectiveness of a case management and housing program in reducing use of urgent medical services among homeless adults with chronic medical illnesses . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial conducted at a public teaching hospital and a private , nonprofit hospital in Chicago , Illinois . Participants were 407 social worker-referred homeless adults with chronic medical illnesses ( 89 % of referrals ) from September 2003 until May 2006 , with follow-up through December 2007 . Analysis was by intention-to-treat . INTERVENTION Housing offered as transitional housing after hospitalization discharge , followed by placement in long-term housing ; case management offered on-site at primary study sites , transitional housing , and stable housing sites . Usual care participants received st and ard discharge planning from hospital social workers . MAIN OUTCOME MEASURES Hospitalizations , hospital days , and emergency department visits measured using electronic surveillance , medical records , and interviews . Models were adjusted for baseline differences in demographics , insurance status , prior hospitalization or emergency department visit , human immunodeficiency virus infection , current use of alcohol or other drugs , mental health symptoms , and other factors . RESULTS The analytic sample ( n = 405 [ n = 201 for the intervention group , n = 204 for the usual care group ] ) was 78 % men and 78 % African American , with a median duration of homelessness of 30 months . After 18 months , 73 % of participants had at least 1 hospitalization or emergency department visit . Compared with the usual care group , the intervention group had unadjusted annualized mean reductions of 0.5 hospitalizations ( 95 % confidence interval [ CI ] , -1.2 to 0.2 ) , 2.7 fewer hospital days ( 95 % CI , -5.6 to 0.2 ) , and 1.2 fewer emergency department visits ( 95 % CI , -2.4 to 0.03 ) . Adjusting for baseline covariates , compared with the usual care group , the intervention group had a relative reduction of 29 % in hospitalizations ( 95 % CI , 10 % to 44 % ) , 29 % in hospital days ( 95 % CI , 8 % to 45 % ) , and 24 % in emergency department visits ( 95 % CI , 3 % to 40 % ) . CONCLUSION After adjustment , offering housing and case management to a population of homeless adults with chronic medical illnesses result ed in fewer hospital days and emergency department visits , compared with usual care . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00490581 BACKGROUND AND OBJECTIVES : \" Housing First \" has been shown to improve housing stability in homeless individuals with mental illness , but had not been empirically tested in homeless youth . We aim ed to evaluate the effect of \" Housing First \" on housing stability in homeless youth aged 18 to 24 years particip \n Output:\n " }, { "from": "agent", "value": "No clear difference in substance use was seen .\nHF approaches successfully improve housing stability and may improve some aspects of health .\nImplementation of HF would likely reduce homelessness and non-routine health service use without an increase in problematic substance use ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Background Results of pre clinical studies suggest that the GABAB receptor agonist baclofen may be useful in treatment of opioid dependence . This study was aim ed at assessing the possible efficacy of baclofen for maintenance treatment of opioid dependence . Methods A total of 40 opioid-dependent patients were detoxified and r and omly assigned to receive baclofen ( 60 mg/day ) or placebo in a 12-week , double blind , parallel-group trial . Primary outcome measure was retention in treatment . Secondary outcome measures included opioids and alcohol use according to urinalysis and self-report ratings , intensity of opioid craving assessed with a visual analogue scale , opioid withdrawal symptoms as measured by the Short Opiate Withdrawal Scale and depression scores on the Hamilton inventory . Results Treatment retention was significantly higher in the baclofen group . Baclofen also showed a significant superiority over placebo in terms of opiate withdrawal syndrome and depressive symptoms . Non-significant , but generally favorable responses were seen in the baclofen group with other outcome measures including intensity of opioid craving and self-reported opioid and alcohol use . However , no significant difference was seen in the rates of opioid-positive urine tests . Additionally , the drug side effects of the two groups were not significantly different . Conclusion The results support further study of baclofen in the maintenance treatment of opioid dependence Background : The clinical use of naltrexone ( NTX ) in the treatment of opioid dependence has been limited because of poor compliance and inconsistent outcomes . In particular , the therapeutic benefit of extended treatment with NTX after opioid detoxification is unclear . The present study evaluated whether the augmentation with low-dose NTX during the post-detoxification treatment of opioid dependence would improve outcomes . Methods : In an open-label naturalistic design , 435 opioid-dependent patients who had completed inpatient detoxification were offered the choice of entering 1 of the 2 outpatient treatment arms : clonidine extended treatment ( CET ) ( clonidine + psychosocial treatment ) , or enhanced extended treatment ( EET ) ( oral NTX [ 1 - 10 mg/d ] + CET ) for 21 days . The primary outcome measure was retention in treatment . Secondary outcomes included abstinence from opioids , dropouts , and adherence to postdischarge care . Results : One hundred sixty-two patients ( 37.2 % ) accepted EET . Subjects receiving EET stayed longer in the program ( F = 64.4 ; P = 0.000 ) , were less likely to drop out , used less opioids , and followed through with referral to long-term outpatient treatment in a higher number , compared with patients in the CET arm ( P = 0.000 in each case ) . The NTX + clonidine combination was safe and well tolerated . Conclusions : This preliminary study indicates the potential benefit of augmentation with low-dose NTX to improve outcomes after opioid detoxification for a preferred group of patients . R and omized controlled trials are necessary to further evaluate the role of low-dose NTX in the outpatient treatment of opioid dependence CONTEXT The usual treatment for opioid-addicted youth is detoxification and counseling . Extended medication-assisted therapy may be more helpful . OBJECTIVE To evaluate the efficacy of continuing buprenorphine-naloxone for 12 weeks vs detoxification for opioid-addicted youth . DESIGN , SETTING , AND PATIENTS Clinical trial at 6 community programs from July 2003 to December 2006 including 152 patients aged 15 to 21 years who were r and omized to 12 weeks of buprenorphine-naloxone or a 14-day taper ( detox ) . INTERVENTIONS Patients in the 12-week buprenorphine-naloxone group were prescribed up to 24 mg per day for 9 weeks and then tapered to week 12 ; patients in the detox group were prescribed up to 14 mg per day and then tapered to day 14 . All were offered weekly individual and group counseling . MAIN OUTCOME MEASURE Opioid-positive urine test result at weeks 4 , 8 , and 12 . RESULTS The number of patients younger than 18 years was too small to analyze separately , but overall , patients in the detox group had higher proportions of opioid-positive urine test results at weeks 4 and 8 but not at week 12 ( chi(2)(2 ) = 4.93 , P = .09 ) . At week 4 , 59 detox patients had positive results ( 61 % ; 95 % confidence interval [ CI ] = 47%-75 % ) vs 58 12-week buprenorphine-naloxone patients ( 26 % ; 95 % CI = 14%-38 % ) . At week 8 , 53 detox patients had positive results ( 54 % ; 95 % CI = 38%-70 % ) vs 52 12-week buprenorphine-naloxone patients ( 23 % ; 95 % CI = 11%-35 % ) . At week 12 , 53 detox patients had positive results ( 51 % ; 95 % CI = 35%-67 % ) vs 49 12-week buprenorphine-naloxone patients ( 43 % ; 95 % CI = 29%-57 % ) . By week 12 , 16 of 78 detox patients ( 20.5 % ) remained in treatment vs 52 of 74 12-week buprenorphine-naloxone patients ( 70 % ; chi(2)(1 ) = 32.90 , P < .001 ) . During weeks 1 through 12 , patients in the 12-week buprenorphine-naloxone group reported less opioid use ( chi(2)(1 ) = 18.45 , P < .001 ) , less injecting ( chi(2)(1 ) = 6.00 , P = .01 ) , and less non study addiction treatment ( chi(2)(1 ) = 25.82 , P < .001 ) . High levels of opioid use occurred in both groups at follow-up . Four of 83 patients who tested negative for hepatitis C at baseline were positive for hepatitis C at week 12 . CONCLUSIONS Continuing treatment with buprenorphine-naloxone improved outcome compared with short-term detoxification . Further research is necessary to assess the efficacy and safety of longer-term treatment with buprenorphine for young individuals with opioid dependence . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00078130 It is estimated that more than 500 000 people in the United States are dependent on opioids [ 1 , 2 ] . Methadone , a synthetic opioid first reported as a treatment agent for opioid dependence by Dole and Nysw and er in 1965 [ 3 ] , is the most widely used pharmacologic treatment for opioid dependence . The National Drug and Alcoholism Treatment Unit Survey ( NDATUS ) determined a point prevalence of 92 715 opioid abusers treated in 758 methadone treatment programs on 30 September 1989 [ 4 ] . When used in conjunction with counseling services , methadone treatment has been associated with reduced rates of criminal activity , illicit drug use , and needle sharing and with improved rates of employment [ 5 - 9 ] . With the recognition of intravenous drug use as a primary risk factor for infection with human immunodeficiency virus ( HIV ) , improved access to methadone treatment has been identified as an important means for reducing the risk of HIV infection [ 10 , 11 ] . Although methadone treatment is effective in decreasing opioid use , recent studies have reported considerable variability across clinics in rates of continued intravenous drug use during treatment [ 12 ] . One aspect of this problem is that intravenous use of cocaine has become a serious problem among methadone treatment patients [ 13 - 16 ] . Few systematic studies have addressed the efficacy of methadone treatment since the onset of the cocaine epidemic [ 17 ] . Such research could re-evaluate in a contemporary population sample methadone 's specific pharmacologic efficacy in decreasing opioid use [ 18 - 20 ] while providing new information about any potential effect of methadone treatment on concurrent cocaine use . The issue of appropriate methadone dosing levels is highly pertinent because low-dose treatment has been strongly associated with poor drug use outcomes in descriptive clinical studies [ 12 , 21 ] and because a substantial number of clinics continue to use low doses of methadone [ 22 ] . For example , a report prepared by the General Accounting Office ( GAO ) that summarized the dosing practice s of 24 methadone programs in eight states found that doses ranged widely ( from 21 to 68 mg ) and 29 % had a mean dose of less than 40 mg [ 23 ] . Thus , despite more than 25 years of clinical experience , optimal dosing levels of methadone remain controversial [ 24 , 25 ] . Previous studies of methadone dosing have either surveyed clinics for their dosing practice and related doses to clinic-wide outcomes or have r and omly assigned patients to a specific predetermined dose of methadone using clinical trial methods . Naturalistic survey studies [ 5 , 6 , 12 , 21 , 26 ] , although valuable for identifying associations between dose and outcome , are method ologically compromised by confounding factors that differ across the clinics surveyed . Previous early clinical trials of methadone dosing [ 27 - 29 ] are also method ologically compromised ( for example , being single-blinded ) or only tested higher doses of methadone [ 30 ] . Thus there is a need for well-controlled research on methadone dosing reflecting doses in common use and incorporating the changing patient population . In this controlled clinical trial we compared moderate and low methadone dosing to methadone-free treatment , providing data in a contemporary population sample of opioid addicts and examining the effect of methadone dose on cocaine as well as opioid use . Methods Participants were 247 persons who had consecutive admissions to a methadone research clinic from September 1988 through July 1990 . The mean age was 34 years , 70 % were male , and 50 % were black . Most were unmarried ( 84 % ) and unemployed ( 62 % ) . They had an average of 11 years of education , were generally legally free ( 72 % ) , and had a mean of two previous admissions for drug abuse treatment . Their primary drug of choice was intravenous heroin , and 47 % reported using cocaine in the 30 days before their application to treatment . Eligibility criteria for study participation were age between 18 and 50 years , history of intravenous opioid dependence ( including documentation of previous treatment for opioid dependence or legal involvement secondary to opioid use , a urine sample positive for opioids , and physical examination consistent with acute and chronic needle use ) , no chronic medical illnesses , absence of a major mental illness , a negative pregnancy test for women , and at least 3 months since the patient 's last treatment at the clinic . Applicants who failed to fulfill the study 's eligibility criteria were assisted in seeking an alternate treatment program . The study was approved by the institutional review board , and informed consent was obtained from each patient at the time of admission to the study . Study Procedures Applicants who fulfilled the eligibility criteria were admitted to a 6-month short-term methadone treatment program . Participants were stratified as to race and sex and were assigned to one of three fixed-dose methadone schedules ( Figure 1 ) . Treatment group assignment , stabilization doses , and dosing schedules were double-blind for all patients and the clinic staff who had patient contact . All patients received a minimum of 35 days of active methadone during the first 5 weeks of treatment ; this was followed by a 15-week stabilization period at either 50 , 20 , or 0 mg of methadone . Thus , patients assigned to the 0-mg treatment group received 35-day methadone detoxification . During weeks 21 through 26 , the methadone dose was gradually tapered for those patients still receiving active medication because this was a short-term ( 182-day ) treatment episode . A sub sample of patients ( n = 44 ) assigned to the 0-mg treatment group received a more prolonged ( 8-week ) induction period , reaching 0 mg at the start of week 9 to compare the effects of a faster to a slower detoxification protocol . In this report data for patients in the alternate 0-mg treatment groups are collapsed . Figure 1 . Dosing schedule . Treatment Procedures Patients were assigned an individual counselor who set treatment goals and developed an individualized treatment plan . Patients were given weekly group therapy focusing on relapse prevention . On-site medical services were provided by a full-time internist and a part-time nurse practitioner . Take-home medication was provided only on legal holidays and for documented extenuating circumstances ( for example , funeral out of town for a death in the family ) . Patients who failed to attend the clinic for 3 consecutive days were discharged from treatment . Outcome Measures Treatment Retention and Compliance Treatment retention was calculated as the total number of days between the day of admission and the day of discharge , or the last day of the stable dosing period ( day 140 ) if the patient remained in treatment beyond the stable dosing period . Compliance with treatment was assessed through treatment attendance , the number of days medicated divided by days in treatment , and counseling contacts \n Output:\n " }, { "from": "agent", "value": "Comparisons showed a statistically significant difference between groups ; higher doses of buprenorphine increased the probability of retention in treatment .\nIt is not possible to conclude about the use of any kind of pharmacologic therapies for maintenance treatment of opium dependence" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Objective To examine the role of the variants of the PTPN22 and HLA – DRB1 genes as predictors of mortality in inflammatory polyarthritis ( IP ) and rheumatoid arthritis ( RA ) . Methods Patients were recruited from a primary care – based inception cohort of patients with IP and were followed up prospect ively . For patients who died , the cause and date of death was obtained . Cox proportional hazards regression models were used to assess the association of the HLA – DRB1 ( including the shared epitope [ SE ] ) and PTPN22 genes with the risk of death from all causes and from cardiovascular disease ( CVD ) and to assess the interactions between SE , smoking , and anti – cyclic citrullinated peptide ( anti-CCP ) status , adjusted by age at symptom onset and sex . Results DNA sample s were available from 1,022 IP patients . During followup , 751 of them ( 74 % ) satisfied the American College of Rheumatology 1987 criteria for RA , and 242 of them ( 24 % ) died . Carriage of 2 copies of SE alleles predicted death from all causes ( hazard ratio [ HR ] 1.57 [ 95 % confidence interval ( 95 % CI ) 1.1–2.2 ] ) and from CVD ( HR 1.68 [ 95 % CI 1.1–2.7 ] ) . This effect was most marked for individuals with the HLA – DRB1 * 01/*04 combination . An interaction of smoking , SE alleles , and anti-CCP antibodies was observed and was associated with the greatest risk of death from CVD ( HR 7.81 [ 95 % CI 2.6–23.2 ] ) . No association of the PTPN22 gene with mortality was detected . Conclusion SE alleles , particularly compound heterozygotes , are associated with death from all causes and from CVD , independently of autoantibody status . However , the combination of SE , smoking , and anti-CCP antibodies is associated with a high risk of premature death in patients with IP and RA , which raises the possibility of a targeted strategy to prevent CVD in these patients OBJECTIVE Heart failure is an important cause of death in patients with rheumatoid arthritis ( RA ) . Evidence suggests that immune mechanisms contribute to myocardial injury and fibrosis , leading to left ventricular diastolic dysfunction ( LVDD ) . The purpose of this study was to identify a signature of LVDD in patients with RA by analyzing the responsiveness of the innate and adaptive immune systems to stimulation ex vivo . METHODS RA patients ( n=212 ) enrolled prospect ively in a population -based cohort underwent echocardiography , and LV function was classified as normal , mild LVDD , or moderate-to-severe LVDD . The release of 17 cytokines by blood mononuclear cells in response to stimulation with a panel of 7 stimuli or in media alone was analyzed using multiplex immunoassays . Logistic regression models were used to test for associations between a multicytokine immune response score and LVDD , after adjusting for clinical covariates . RESULTS An 11-cytokine profile effectively differentiated patients with moderate-to-severe LVDD from those with normal LV function . An immune response score ( range 0 - 100 ) was strongly associated with moderate-to-severe LVDD ( odds ratio per 10 units 1.5 [ 95 % confidence interval 1.2 - 2.1 ] ) after adjusting for serum interleukin-6 levels , brain natriuretic peptide values , and glucocorticoid use , as well as other RA characteristics and LVDD risk factors . CONCLUSION The major finding of this study was that aberrant systemic immune responsiveness is associated with advanced myocardial dysfunction in patients with RA . The unique information added by the immune response score concerning the likelihood of LVDD warrants future longitudinal studies of its value in predicting future deterioration in myocardial function BACKGROUND The objective of this study was to examine the association of Joint National Committee ( JNC-V ) blood pressure and National Cholesterol Education Program ( NCEP ) cholesterol categories with coronary heart disease ( CHD ) risk , to incorporate them into coronary prediction algorithms , and to compare the discrimination properties of this approach with other noncategorical prediction functions . METHODS AND RESULTS This work was design ed as a prospect i ve , single-center study in the setting of a community-based cohort . The patients were 2489 men and 2856 women 30 to 74 years old at baseline with 12 years of follow-up . During the 12 years of follow-up , a total of 383 men and 227 women developed CHD , which was significantly associated with categories of blood pressure , total cholesterol , LDL cholesterol , and HDL cholesterol ( all P<.001 ) . Sex-specific prediction equations were formulated to predict CHD risk according to age , diabetes , smoking , JNC-V blood pressure categories , and NCEP total cholesterol and LDL cholesterol categories . The accuracy of this categorical approach was found to be comparable to CHD prediction when the continuous variables themselves were used . After adjustment for other factors , approximately 28 % of CHD events in men and 29 % in women were attributable to blood pressure levels that exceeded high normal ( > or = 130/85 ) . The corresponding multivariable-adjusted attributable risk percent associated with elevated total cholesterol ( > or = 200 mg/dL ) was 27 % in men and 34 % in women . CONCLUSIONS Recommended guidelines of blood pressure , total cholesterol , and LDL cholesterol effectively predict CHD risk in a middle-aged white population sample . A simple coronary disease prediction algorithm was developed using categorical variables , which allows physicians to predict multivariate CHD risk in patients without overt CHD Objective : Rheumatoid arthritis ( RA ) patients have an increased risk of developing cardiovascular diseases ( CVD ) . Other autoimmune diseases such as hypothyroidism are also associated with an enhanced risk for CVD . Our objective was to determine first , the prevalence of hypothyroid disorders in RA patients , and second , the risk of CVD in RA patients with hypothyroid abnormalities . Methods : Subjects were RA patients who participated in an ongoing prospect i ve cohort study of cardiovascular mortality and morbidity ( n = 358 ) in which hypothyroid abnormalities were assessed . CVD was defined as a verified medical history of coronary , cerebral or peripheral arterial disease . Results : Clinical hypothyroidism was observed in 16 of 236 female RA patients ( 6.8 % ) , which is significantly higher than in the general population of The Netherl and s. Sub clinical hypothyroidism was detected in 6 out of 236 RA women ( 2.5 % ) . In female RA patients , CVD was present in 6 out of 16 ( 37.5 % ) of all hypothyroid women . The odds ratio for CVD comparing female hypothyroid RA patients with female euthyroid RA patients was 4.1 ( 95 % CI 1.2–14.3 ) after adjustment for sex , age , diabetes , smoking ( ever ) , hypertension and statin use . Conclusions : Clinical hypothyroidism was observed three times more often in female RA patients than females in the general population . In female RA patients , clinical hypothyroidism was associated with a fourfold higher risk of CVD in comparison with euthyroid female RA patients independently of the traditional risk factors Introduction In this study , we aim ed to determine the relationship between flow-mediated endothelium-dependent vasodilatation ( FMD ) and carotid artery intima-media wall thickness ( IMT ) , two surrogate markers of atherosclerosis , in a series of Spanish patients with rheumatoid arthritis ( RA ) without clinical ly evident cardiovascular ( CV ) disease . Methods One hundred eighteen patients who fulfilled the 1987 American College of Rheumatology classification criteria for RA , had no history of CV disease and had at least one year of follow-up after disease diagnosis were r and omly selected . Brachial and carotid ultrasonography were performed to determine FMD and carotid IMT , respectively . Results Carotid IMT values were higher and FMD percentages derived by performing ultrasonography were lower in individuals with a long duration from the time of disease diagnosis . Patients with a disease duration ≤ 7 years had significantly lower carotid IMT ( mean ± SD ) 0.69 ± 0.17 mm than those with long disease duration ( 0.81 ± 0.12 mm in patients with ≥ 20 years of follow-up ) . Also , patients with a long disease duration had severe endothelial dysfunction ( FMD 4.0 ± 4.0 % in patients with disease duration from 14.5 to 19.7 years ) compared with those with shorter disease duration ( FMD 7.4 ± 3.8 % in patients with disease duration ≤ 7 years ) . Linear regression analysis revealed that carotid IMT was unrelated to FMD in the whole sample of 118 patients . However , carotid IMT was negatively associated with FMD when the time from disease diagnosis ranged from 7.5 to 19.7 years ( P = 0.02 ) . Conclusions In patients with RA without CV disease , endothelial dysfunction and carotid IMT increased with the duration of RA . The association between FMD and carotid IMT values was observed only in patients with long disease duration OBJECTIVE To investigate the prospect i ve effect of hemostatic factors and inflammatory variables on the progression of cardiovascular disease in rheumatoid arthritis ( RA ) . METHODS Von Willebr and factor ( vWF ) and the fibrinolytic factors tissue plasminogen activator ( tPA ) , measured as tPA capacity , and plasminogen activator inhibitor 1 ( PAI-1 ) , platelets , fibrinogen , and inflammatory markers were measured in 74 patients with active seropositive RA . Lipid levels , lipoprotein(a ) , and cardiolipin antibodies were also analyzed . Cardiovascular disease , measured by past cardiovascular events including thrombotic events , was registered in an 8 year followup . RESULTS Patients with a cardiovascular event during the followup period ( n = 26 ) had significantly higher levels of vWF , PAI-1 , erythrocyte sedimentation rate ( ESR ) , and haptoglobin at entry to the study . In a multiple logistic regression model controlling for several conventional cardiovascular risk factors and pharmacological treatment at sampling , PAI-1 and tPA were significantly associated with cardiovascular disease progression . CONCLUSION The altered levels of vWF , PAI-1 , and , in logistic regression , tPA in RA patients with cardiovascular disease progression indicates a status of hypofibrinolysis in these patients . Higher levels of ESR and haptoglobin may reflect the importance of the inflammatory process for the development of cardiovascular disease in RA OBJECTIVE To assess the risk of acute myocardial infa rct ion ( AMI ) associated with the use of disease-modifying antirheumatic drugs ( DMARDs ) and other medications commonly used in rheumatoid arthritis ( RA ) . METHODS We conducted a nested case-control analysis within a cohort of subjects with RA , observed between 1999 and 2003 , identified from the PharMetrics cl aims data base . For each first AMI hospitalization identified during followup , 10 controls matched on sex , age , and time of study entry were r and omly selected from the cohort . Conditional logistic regression was used to estimate the rate ratio ( RR ) of AMI associated with the current use of anti-RA therapy , as measured from dispensed prescriptions , after adjustment for AMI risk factors . RESULTS The cohort included 107,908 subjects ( average age 54 years at cohort entry ) . During followup , 558 AMI cases occurred ( 3.4 per 1,000 per year ) . AMI rate was significantly decreased with the current use of any DMARD ( adjusted RR 0.80 , 95 % confidence interval [ 95 % CI ] 0.65 - 0.98 ) . This effect was consistent across all DMARDs , including methotrexate ( RR 0.81 , 95 % CI 0.60 - 1.08 ) , leflunomide ( RR 0.28 , 95 % CI 0.12 - 0.65 ) , and other traditional DMARDs ( RR 0.67 , 95 % CI 0.46 - 0.97 ) , but not biologic agents ( RR 1.30 , 95 % CI 0.92 - 1.83 ) . AMI rate increased with the use of glucocorticoids ( RR 1.32 , 95 % CI 1.02 - 1.72 ) but not with nonselective nonsteroidal antiinflammatory drugs ( RR 1.05 , 95 % CI 0.81 - 1.36 ) or cyclooxygenase 2 ( COX-2 ) inhibitors ( RR 1.11 , 95 % CI 0.87 - 1.43 ) . CONCLUSION DMARD use is associated with a reduction in AMI risk in patients with RA . No risk increase was found with the COX-2 inhibitors in this population OBJECTIVE The risk of cardiovascular disease ( CVD ) is increased in patients with rheumatoid arthritis ( RA ) . The objective of this study was to examine the distribution of known CVD risk factors and \n Output:\n " }, { "from": "agent", "value": "Hypercholesterolemia , type 2 diabetes mellitus , abnormal body mass index , abdominal obesity , and current smoking were all traditional risk factors significantly associated with CVD in Colombians ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: OBJECTIVE To assess the effectiveness of an emergency department (ED)-based home safety intervention on caregivers ' behaviors and practice s related to home safety . METHODS We conducted a r and omized , clinical trial of 96 consecutive caregivers of children who were younger than 5 years and presented to an urban pediatric ED for evaluation of an acute unintentional injury sustained in the home . After completing a structured home safety question naire via face-to-face interview , caregivers were r and omly assigned to receive either comprehensive home safety education and free safety devices or focused , injury-specific ED discharge instructions . Participants were contacted by telephone 2 months after the initial ED visit for repeat administration of the safety question naire . The pretest and posttest question naires were scored such that the accrual of points correlated with reporting of safer practice s. Scores were then normalized to a 100-point scale . The overall safety score reflected performance on the entire question naire , and the 8 category safety scores reflected performance in single areas of home injury prevention ( fire , burn , poison , near-drowning , aspiration , cuts/piercings , falls , and safety device use ) . The main outcome was degree of improvement in safety practice s as assessed by improvement in safety scores . RESULTS The intervention group demonstrated a significantly higher average overall safety score at follow-up than the control group ( 73.3 % + /- 8.4 % vs 66.8 % + /-11.1 ) and significant improvements in poison , cut/piercing , and burns category scores . Caregivers in the intervention group also demonstrated greater improvement in reported use of the distributed safety devices . CONCLUSIONS This educational and device disbursement intervention was effective in improving the home safety practice s of caregivers of young children . Moreover , the ED was used effectively to disseminate home injury prevention information In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objective : to evaluate the effectiveness of a school-based injury prevention program . Design : Cluster r and omised controlled trial . Setting : 20 primary schools in Nottingham , UK . Participants : 459 children aged 7 to 10 years . Intervention : The “ Risk Watch ” program delivered by teachers , aim ed at improving bike and pedestrian , falls , poisoning and fire and burns safety . Main outcome measures : Safety knowledge , observed safety skills and self-reported safety behaviour . Results : At follow-up , intervention group children correctly answered more fire and burn prevention knowledge questions than control group children ( difference between means 7.0 % ( 95 % CI 1.5 % to12.6 % ) ) . Children in intervention group schools were more likely to know the correct actions to take if clothes catch fire and the correct way to wear a cycle helmet ( difference between school means 35.3 % ( 95 % CI 22.7 % to 47.9 % ) and 6.3 % ( 95 % CI 1.4 % to 11.1 % ) respectively ) . They were also more likely to know the correct actions to take in a house fire and on finding tablets ( OR 2.80 ( 95 % CI 1.08 to 7.22 ) and OR 3.50 ( 95 % CI 1.18 to 10.38 ) respectively ) and correctly demonstrated more safety skills than control group children ( difference between means 11.9 % ( 95 % CI 1.4 % to 22.5 % ) ) . There was little evidence to suggest the first year of the program impacted on self-reported safety behaviours . Conclusions : The Risk Watch program delivered by teachers in primary schools increased some aspects of children ’s safety knowledge and skills and primary schools should consider delivering this program . Longer term , larger scale evaluations are required to examine retention of knowledge and skills and impact on safety behaviours and child injury rates In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies , most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted Background Toddler-aged children are vulnerable to unintentional injuries , especially those in low-income families . Objective To examine the effectiveness of an intervention grounded in social cognitive theory ( SCT ) on the reduction of home safety problems among low-income families with toddlers . Methods 277 low-income mother – toddler dyads were r and omised into a safety promotion intervention ( n=91 ) or an attention-control group ( n=186 ) . Mothers in the safety promotion intervention group received an eight-session , group-delivered safety intervention targeting fire prevention , fall prevention , poison control and car seat use , through health education , goal - setting and social support . Data collectors observed participants ' homes and completed a nine-item checklist of home safety problems at study enrolment ( baseline ) , 6 and 12 months after baseline . A total score was summed , with high scores indicating more problems . Linear mixed models compared the changes over time in home safety problems between intervention and control groups . Results The intent-to-treat analysis indicated that the safety promotion intervention group significantly reduced safety problems to a greater degree than the attention-control group at the 12-month follow-up ( between-group difference in change over time β=−0.54 , 95 % CI −0.05 to −1.03 , p=0.035 ) , with no significant differences at the 6-month follow-up . Conclusions A safety promotion intervention built on principles of SCT has the potential to promote toddlers ' home safety environment . Future studies should examine additional strategies to determine whether better penetration/compliance can produce more clinical ly important improvement in home safety practice s. Trial registration number NCT02615158 ; post- results This study offers evidence that computer-based instruction is a feasible and effective alternative training method for long-term care staff . Participants were 289 nursing facility staff r and omly divided into two treatment groups . One group completed instructor-led ( IL ) fire safety training and the other completed computer-based ( CB ) training adapted from the IL version . Both the CB and IL groups significantly increased their scores from pre- to posttest . Differences between the two groups were not significant The objective of this study was to determine the impact of a community based fire prevention intervention directed only to parents on the fire safety knowledge and behavior in elementary school children . This was a prospect i ve , quasi-r and omized controlled study in which third and fourth grade students from two elementary schools in an urban , poor , minority community completed knowledge/behavior surveys at baseline and following completion of the intervention . The intervention group received an in-home visit from fire department personnel who installed free lithium smoke detectors and provided a fire escape plan . After accounting for a small difference in baseline summary scores of knowledge and behavior between the control and intervention groups , this study found a modest improvement in fire safety behavior among children whose families received a fire prevention intervention reflecting a change in household fire safety practice s. However , there was no significant change in fire safety knowledge Background Fires and burns are a leading cause of unintentional injury death in the USA . Although it has been anecdotally reported that vacant dwellings are at a higher risk for fire , the association between vacancy and fire risk at the individual household level has not been empirically measured . Methods In this cross-sectional study , geocoded residential vacant properties ( VP ) and fire events are analysed in Baltimore City at the census tract level and the individual household level . Results On average , a 10 % increase in the proportion of vacancies in a census tract was associated with a 9.9 % increase in fires ( 95 % CI : 5 % to 15 % ) . R and om-effects Poisson models , controlling for housing and neighbourhood conditions , found contagion effects . The risk of fire in an occupied dwelling increased by 8 % ( 95 % CI : 1 % to 10 % ) for every vacant structure within 10 m , and the risk of fire decreased by half ( 95 % CI : 45 % to 62 % ) for every km between an occupied dwelling and vacant building . Close proximity to VP was associated with trash fires within dwellings ( p=0.039 ) and structure fires ( p=0.012 ) . Conclusions We believe that this is the first study to demonstrate increased risk posed by nearby VP at the household level , confirming earlier ecological analyses of the role of VP as strong correlates of home fires . Measurement of this risk can motivate property owners , policy makers and insurers to invest in risk reduction measures that include building maintenance and trash removal OBJECTIVE Fire is a leading cause of unintentional injury and , although young children are at particularly increased risk , there are very few evidence -based re sources available to teach them fire safety knowledge and behaviors . Using a pre-post r and omized design , the current study evaluated the effectiveness of a computer game ( The Great Escape ) for teaching fire safety information to young children ( 3.5 - 6 years ) . METHOD Using behavioral enactment procedures , children 's knowledge and behaviors related to fire safety were compared to a control group of children before and after receiving the intervention . RESULTS The results indicated significant improvements in knowledge and fire safety behaviors in the intervention group but not the control . CONCLUSION Using computer games can be an effective way to promote young children 's underst and ing of safety and how to react in different hazardous situations Background Although proven measures for reducing injury due to motor vehicle collision and residential fires exist , the number of families properly and consistently using child passenger restraints and smoke alarms remains low . This paper describes the design of the Safety In Seconds ( SIS ) 2.0 study , which aims to evaluate the impact of a smartphone app on parents ' use of child restraints and smoke alarms . Methods SIS is a multisite r and omised controlled trial . Participants are parents of children aged 4–7 years who are visiting the Pediatric Emergency Department or Pediatric Trauma Service . Parents are r and omised to receive tailored education about child passenger safety or about fire safety via the SIS smartphone app . A baseline and two follow-up surveys at 3 months and 6 months are conducted . Primary outcomes are : ( 1 ) having the correct child restraint for the child 's age and size ; ( 2 ) restraining the child in the back seat of the car ; ( 3 ) buckling the child up for every ride ; ( 4 ) having the restraint inspected by a child passenger safety technician ; ( 5 ) having a working smoke alarm on every level of the home ; ( 6 ) having hard-wired or lithium battery smoke alarms ; ( 7 ) having and ( 8) practising a fire escape plan . Discussion Finding ways to communicate with parents about child passenger and fire safety continues to be a research priority . This study will contribute to the evidence about how to promote benefits of proper and consistent child restraint and smoke alarm use . Trial registration number NCT02345941 ; Pre- results \n Output:\n " }, { "from": "agent", "value": "The limited evidence supports the use of HFS interventions to improve HFS knowledge and behaviour in children , families with children and adults" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Purpose The aim of our study was to compare the diagnostic performance of 68Ga-PSMA PET and 99mTc bone scintigraphy ( BS ) for the detection of bone metastases in prostate cancer ( PC ) patients . Methods One hundred twenty-six patients who received planar BS and PSMA PET within three months and without change of therapy were extracted from our data base . Bone lesions were categorized into benign , metastatic , or equivocal by two experienced observers . A best valuable comparator ( BVC ) was defined based on BS , PET , additional imaging , and follow-up data . The cohort was further divided into clinical subgroups ( primary staging , biochemical recurrence , and metastatic castration-resistant prostate cancer [ mCRPC ] ) . Additionally , subgroups of patients with less than 30 days delay between the two imaging procedures and with additional single-photon emission computed tomography ( SPECT ) were analyzed . Results A total of 75 of 126 patients were diagnosed with bone metastases . Sensitivities and specificities regarding overall bone involvement were 98.7–100 % and 88.2–100 % for PET , and 86.7–89.3 % and 60.8–96.1 % ( p < 0.001 ) for BS , with ranges representing results for ‘ optimistic ’ or ‘ pessimistic ’ classification of equivocal lesions . Out of 1115 examined bone regions , 410 showed metastases . Region-based analysis revealed a sensitivity and specificity of 98.8–99.0 % and 98.9–100 % for PET , and 82.4–86.6 % and 91.6–97.9 % ( p < 0.001 ) for BS , respectively . PSMA PET also performed better in all subgroups , except patient-based analysis in mCRPC . Conclusion Ga-PSMA PET outperforms planar BS for the detection of affected bone regions as well as determination of overall bone involvement in PC patients . Our results indicate that BS in patients who have received PSMA PET for staging only rarely offers additional information ; however , prospect i ve studies , including a st and ardized integrated x-ray computed tomography ( SPECT/CT ) protocol , should be performed in order to confirm the presented results Purpose The aim of this retrospective two-centre study was to investigate the clinical impact of 11C-choline PET/CT on treatment management decisions in patients with recurrent prostate cancer ( rPCa ) after radical therapy . Methods Enrolled in this retrospective study were 150 patients ( 95 from Bologna , 55 from Würzburg ) with rPCa and biochemical relapse ( PSA mean ± SD 4.3 ± 5.5 ng/mL , range 0.2–39.4 ng/mL ) after radical therapy . The intended treatment before PET/CT was salvage radiotherapy of the prostatic bed in 95 patients and palliative and rogen deprivation therapy ( ADT ) in 55 patients . The effective clinical impact of 11C-choline PET/CT was rated as major ( change in therapeutic approach ) , minor ( same treatment , but modified therapeutic strategy ) or none . Multivariate binary logistic regression analysis included PSA level , PSA kinetics , ongoing ADT , Gleason score , TNM , age and time to relapse . Results Changes in therapy after 11C-choline PET/CT were implemented in 70 of the 150 patients ( 46.7 % ) . A major clinical impact was observed in 27 patients ( 18 % ) and a minor clinical impact in 43 ( 28.7 % ) . 11C-choline PET/CT was positive in 109 patients ( 72.7 % ) detecting local relapse ( prostate bed and /or iliac lymph nodes and /or pararectal lymph nodes ) in 64 patients ( 42.7 % ) . Distant relapse ( paraaortic and /or retroperitoneal lymph nodes and /or bone lesions ) was seen in 31 patients ( 20.7 % ) , and both local and distant relapse in 14 ( 9.3 % ) . A significant difference was observed in PSA level and PSA kinetics between PET-positive and PET-negative patients ( p < 0.05 ) . In multivariate analysis , PSA level , PSA doubling time and ongoing ADT were significant predictors of a positive scan ( p < 0.05 ) . In statistical analysis no significant differences were observed between the Bologna and Würzburg patients ( p > 0.05 ) . In both centres the same criteria to vali date PET-positive findings were used : in 17.3 % of patients by histology and in 82.7 % of patients by correlative imaging and /or clinical follow-up ( follow-up mean 20.5 months , median 18.3 months , range 6.2–60 months ) . Conclusion 11C-Choline PET/CT had a significant impact on therapeutic management in rPCa patients . It led to an overall change in 46.7 % of patients , with a major clinical change implemented in 18 % of patients . Further prospect i ve studies are needed to evaluate the effect of such treatment changes on patient survival In prostate cancer with biochemical failure after therapy , current imaging techniques have a low detection rate at the prostate-specific antigen ( PSA ) levels at which targeted salvage therapy is effective . 11C-choline and 18F-fluoromethylcholine , though widely used , have poor sensitivity at low PSA levels . 68Ga-PSMA ( Glu-NH-CO-NH-Lys-(Ahx)-[68Ga-N , N′-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N , N′-diacetic acid ] ) has shown promising results in retrospective trials . Our aim was to prospect ively compare the detection rates of 68Ga-PSMA versus 18F-fluoromethylcholine PET/CT in men who were initially managed with radical prostatectomy , radiation treatment , or both and were being considered for targeted therapy . Methods : A sample of men with a rising PSA level after treatment , eligible for targeted treatment , was prospect ively included . Patients on systemic treatment were excluded . 68Ga-PSMA , 18F-fluoromethylcholine PET/CT , and diagnostic CT were performed sequentially on all patients between January and April 2015 , and the images were assessed by masked , experienced interpreters . The findings and their impact on management were documented , together with the results of histologic follow-up when feasible . Results : In total , 38 patients were enrolled . Of these , 34 ( 89 % ) had undergone radical prostatectomy and 4 ( 11 % ) had undergone radiation treatment . Twelve ( 32 % ) had undergone salvage radiation treatment after primary radical prostatectomy . The mean PSA level was 1.74 ± 2.54 ng/mL. The scan results were positive in 26 patients ( 68 % ) and negative with both tracers in 12 patients ( 32 % ) . Of the 26 positive scans , 14 ( 54 % ) were positive with 68Ga-PSMA alone , 11 ( 42 % ) with both 18F-fluoromethylcholine and 68Ga-PSMA , and only 1 ( 4 % ) with 18F-fluoromethylcholine alone . When PSA was below 0.5 ng/mL , the detection rate was 50 % for 68Ga-PSMA versus 12.5 % for 18F-fluoromethylcholine . When PSA was 0.5–2.0 ng/mL , the detection rate was 69 % for 68Ga-PSMA versus 31 % for 18F-fluoromethylcholine , and when PSA was above 2.0 , the detection rate was 86 % for 68Ga-PSMA versus 57 % for 18F-fluoromethylcholine . On lesion-based analysis , 68Ga-PSMA detected more lesions than 18F-fluoromethylcholine ( 59 vs. 29 , P < 0.001 ) . The tumor-to- background ratio in positive scans was higher for 68Ga-PSMA than for 18F-fluoromethylcholine ( 28.6 for 68Ga-PSMA vs. 9.4 for 18F-fluoromethylcholine , P < 0.001 ) . There was a 63 % ( 24/38 patients ) management impact , with 54 % ( 13/24 patients ) being due to 68Ga-PSMA imaging alone . Histologic follow-up was available for 9 of 38 patients ( 24 % ) , and 9 of 9 68Ga-PSMA – positive lesions were consistent with prostate cancer ( 68Ga-PSMA was true-positive ) . The lesion positive on 18F-fluoromethylcholine imaging and negative on 68Ga-PSMA imaging was shown at biopsy to be a false-positive 18F-fluoromethylcholine finding ( 68Ga-PSMA was true-negative ) . Conclusion : In patients with biochemical failure and a low PSA level , 68Ga-PSMA demonstrated a significantly higher detection rate than 18F-fluoromethylcholine and a high overall impact on management This prospect i ve pilot study evaluated the ability of Na18F PET/CT to detect and monitor bone metastases over time and its correlation with clinical outcomes and survival in advanced prostate cancer . Methods : Sixty prostate cancer patients , including 30 with and 30 without known bone metastases by conventional imaging , underwent Na18F PET/CT at baseline , 6 mo , and 12 mo . Positive lesions were verified on follow-up scans . Changes in SUVs and lesion number were correlated with prostate-specific antigen change , clinical impression , and overall survival . Results : Significant associations included the following : SUV and prostate-specific antigen percentage change at 6 mo ( P = 0.014 ) and 12 mo ( P = 0.0005 ) ; SUV maximal percentage change from baseline and clinical impression at 6 mo ( P = 0.0147 ) and 6–12 mo ( P = 0.0053 ) ; SUV change at 6 mo and overall survival ( P = 0.018 ) ; number of lesions on Na18F PET/CT and clinical impression at baseline ( P < 0.0001 ) , 6 mo ( P = 0.0078 ) , and 12 mo ( P = 0.0029 ) ; and number of lesions on Na18F PET/CT per patient at baseline and overall survival ( P = 0.017 ) . In an exploratory analysis , paired 99mTc-methylene diphosphonate bone scans ( 99mTc-BS ) were available for 35 patients at baseline , 19 at 6 mo , and 14 at 12 mo ( 68 scans ) . Malignant lesions on Na18F PET/CT ( n = 57 ) were classified on 99mTc-BS as malignant 65 % of the time , indeterminate 25 % of the time , and negative 10 % of the time . Additionally , 69 % of paired scans showed more lesions on Na18F PET/CT than on 99mTc-BS . Conclusion : The baseline number of malignant lesions and changes in SUV on follow-up Na18F PET/CT significantly correlate with clinical impression and overall survival . Na18F PET/CT detects more bone metastases earlier than 99mTc-BS and enhances detection of new bone disease in high-risk patients \n Output:\n " }, { "from": "agent", "value": "Conclusions According to the meta- analysis , PSMA-PET/CT had the highest per-patient sensitivity and specificity in detecting bone metastases with prostate cancer .\nThe sensitivities of NaF-PET/CT and MRI were better than those for choline-PET/CT and BS .\nThe specificity of PSMA-PET/CT was significantly better than BS .\nOthers were similar .\nFor per-lesion , NaF-PET/CT had the highest sensitivity , PSMA-PET/CT had higher sensitivity than choline-PET/CT and MRI , and BS had the lowest sensitivity" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: PURPOSE Viable bacteria are often isolated from airway secretions in clinical ly stable patients with chronic bronchitis . We hypothesized that the number of organisms and bacterial species might be important modulators of airway inflammation . SUBJECTS AND METHODS We performed quantitative sputum cultures in 160 stable patients [ 55 with chronic obstructive pulmonary disease ( COPD ) and normal serum alpha(1)-antitrypsin levels , 62 with COPD and severe alpha(1)-antitrypsin deficiency ( PiZ ) , and 43 with idiopathic bronchiectasis ] . The results were related to several indicators of the mechanisms and severity of airway inflammation . RESULTS Airway bacterial load correlated with sputum myeloperoxidase level , an indirect measure of neutrophil activation and number ( r = 0.50 , P<0 . 001 ) ; sputum neutrophil chemoattractants [ interleukin-8 level ( r = 0 . 68 , P<0.001 ) and leukotriene B4 level ( r = 0.53 , P<0.001 ) ] ; sputum leukocyte elastase activity ( r = 0.55 , P<0.001 ) ; and albumin leakage from serum to sputum ( r = 0.26 , P<0.01 ) . Markers of inflammation increased at bacterial loads of 10(6 ) to 10(7 ) colony-forming units per milliliter , and increased progressively with increasing bacterial load . For example , the median ( interquartile range ) sputum myeloperoxidase level was 0.3 U/mL ( 0.1 to 0.5 U/mL ) for patients who were not colonized or who had mixed normal oropharyngeal flora alone ; 0.5 U/mL ( 0.2 to 0.7 U/mL ) for patients with 10(5 ) to 10(6 ) colony-forming units per milliliter ( P = 0.07 ) ; 0.5 U/mL ( 0.3 to 1.2 U/mL ) for patients with 10(6 ) to 10(7 ) colony-forming units per milliliter ( P<0.01 ) ; 0.7 U/mL ( 0.3 to 1.2 U/mL ) for patients with 10(7 ) to 10(8 ) colony-forming units per milliliter ( P < 0.005 ) ; and 2.4 U/mL ( 0.7 to 4.8 U/mL ) for patients with 10(8 ) or greater colony-forming units per milliliter ( P<0.0001 ) . The bacterial species influenced airway inflammation ; for example , sputum myeloperoxidase activity was greater ( P<0.005 ) in patients colonized with Pseudomonas aeruginosa [ median 32 U/mL ( interquartile range , 20 to 65 U/mL ) ] than those colonized with nontypeable Hemophilus influenzae [ 4 U/mL ( 2 to 31 U/mL ) ] , which in turn was greater ( P = 0.01 ) than among those colonized with Moraxella catarrhalis [ 1.1 U/mL ( 0.6 to 1.8 U/mL ) ] . We did not find a relation between bacterial load and lung function . CONCLUSIONS The bacterial load and species contribute to airway inflammation in patients with stable chronic bronchitis . Further studies are required to determine the consequences of bacterial colonization on patient morbidity and decline in lung function UNLABELLED Neutrophil elastase ( NE ) activity is increased in bronchiectasis and may play a role in this condition . We wished to determine the effect of AZD9668 , a selective oral inhibitor of NE . Efficacy and safety of AZD9668 60 mg twice daily over 4 weeks were evaluated in a r and omised , double-blind , placebo-controlled , parallel-group , Phase II , signal- search ing study in patients with bronchiectasis . Outcome measures included : waking and post-waking sputum neutrophil counts ; lung function tests ; 24-h sputum weight ; BronkoTest ( ® ) diary card data ; St George 's Respiratory Question naire for COPD patients ( SGRQ-C ) ; sputum NE activity ; inflammatory biomarker levels ; desmosine levels ; adverse events , safety haematology and biochemistry . AZD9668 levels in plasma and sputum were measured to confirm exposure . Thirty-eight patients were r and omised : 16 to placebo and 22 to AZD9668 . There was no change in sputum neutrophils with AZD9668 . Forced expiratory volume in 1 s improved by 100 mL in the AZD9668 group compared with placebo ( p = 0.006 ) . Significant changes ( defined a priori as p < 0.1 ) in favour of AZD9668 were also seen in slow vital capacity , plasma interleukin-8 , and post-waking sputum interleukin-6 and Regulated on Activation , Normal T-cell Expressed and Secreted levels . Non-significant changes in favour of AZD9668 were seen in other lung function tests , sputum weight and the SGRQ-C. AZD9668 was well tolerated . In this small signal- search ing study , 4 weeks ' treatment with AZD9668 improved lung function in patients with bronchiectasis and there were trends for reductions in sputum inflammatory biomarkers . Larger studies of longer duration would be needed to confirm the potential benefits of this agent in bronchiectasis . REGISTRATION NCT00769119 BACKGROUND Bronchiectasis is a chronic suppurative lung disease characterised by irreversible dilation of the bronchi and persistent purulent sputum . The immunopathology of the disease was studied using a quantitative immunostaining technique with particular reference to T lymphocytes , macrophages , and granulocytes . METHODS Bronchial mucosal biopsy specimens were obtained by fibreoptic bronchoscopy from 12 patients with bronchiectasis ( six receiving inhaled steroids ) and 11 normal healthy controls . Immunostaining ( APAAP method ) was performed on frozen cryostat sections with a panel of monoclonal antibodies to total leucocytes ( CD45 ) , T lymphocyte phenotypic markers ( CD3 , CD4 , CD8 ) , macrophages ( CD68 ) , eosinophils ( EG2 ) , and neutrophils ( elastase ) . RESULTS There was a mononuclear cell infiltrate in both patients with bronchiectasis and normal controls , but an overall increase in total leucocyte cell numbers ( CD45 + cells ) was identified in those with bronchiectasis ( median values 422 cells/mm2 versus 113 cells/mm2 in control tissue , p<0.001 ) . Intense infiltration of CD3 + T lymphocytes was observed compared with healthy controls ( 292 cells/mm2 and 40 cells/mm2 , respectively , p<0.001 ) . This comprised predominantly CD4 + T cells ( 118 cells/mm2 ) rather than CD8 + T cells ( 47 cells/mm2 ) . CD3 + cell counts were reduced in those subjects on inhaled steroids compared with those not receiving inhaled steroids ( 197 cells/mm2 versus 369 cells/mm2 , p<0.05 ) , as were CD4 + cell counts ( 82 cells/mm2 versus 190 cells/mm2 , p<0.05 ) . Neutrophil and macrophage cell numbers were also increased in patients with bronchiectasis ( 114 cells/mm2 and 213 cells/mm2 , respectively ) compared with controls ( 41 neutrophils/mm2 and 40 macrophages/mm2 ) . EG2 + ( activated ) eosinophil numbers were much lower than T cells , macrophages , and neutrophils in patients with bronchiectasis but were increased compared with controls ( 36 cells/mm2 versus 0 cells/mm2 , p<0.001 ) . In view of the markedly increased neutrophil counts in patients with bronchiectasis , biopsy specimens were immunostained for interleukin 8 ( IL-8 ) which was highly significantly increased compared with controls ( 47 cells/mm2 versus 15 cells/mm2 , p<0.01 ) . IL-8 + cells were less prominent in steroid treated patients than in patients not receiving treatment ( 30 cells/mm2 versus 60 cells/mm2 , p<0.05 ) . A further characteristic of bronchiectasis was mucous gl and hypertrophy . Gl and area comprised up to 40 % of the tissue in some bronchiectasis sections while no hypertrophy was noted in control biopsy specimens ( p<0.05 ) . CONCLUSION Airway inflammation in bronchiectasis is characterised by tissue neutrophilia , a mononuclear cell infiltrate composed mainly of CD4 + T cells and CD68 + macrophages , and increased IL-8 expression . Inhaled corticosteroid treatment in patients with bronchiectasis is associated with a less marked infiltration by T cells and IL-8 + cells within the bronchial mucosa , although this finding requires confirmation in a prospect i ve placebo controlled trial RATIONALE Bronchiectasis is a chronic debilitating disease with few evidence -based long-term treatments . OBJECTIVES A r and omized controlled trial assessing the efficacy of nebulized gentamicin therapy over 1 year in patients with non-cystic fibrosis bronchiectasis . METHODS Sixty-five patients were r and omized to either twice-daily nebulized gentamicin , 80 mg , or nebulized 0.9 % saline , for 12 months . All were review ed at three-monthly intervals during treatment and at 3 months ' follow-up . MEASUREMENTS AND MAIN RESULTS At each review the following were assessed : quantitative and qualitative sputum bacteriology ; sputum purulence and 24-hour volume ; FEV(1 ) , FVC , and forced expiratory flow , midexpiratory phase ; exercise capacity ; Leicester Cough Question naire and St. George 's Respiratory Question naire ; and exacerbation frequency . Fifty-seven patients completed the study . At the end of 12 months ' treatment , compared with the saline group , in the gentamicin group there was reduced sputum bacterial density with 30.8 % eradication in those infected with Pseudomonas aeruginosa and 92.8 % eradication in those infected with other pathogens ; less sputum purulence ( 8.7 % vs. 38.5 % ; P < 0.0001 ) ; greater exercise capacity ( 510 [ 350 - 690 ] m vs. 415 [ 267.5 - 530 ] m ; P = 0.03 ) ; and fewer exacerbations ( 0 [ 0 - 1 ] vs. 1.5 [ 1 - 2 ] ; P < 0.0001 ) with increased time to first exacerbation ( 120 [ 87 - 161.5 ] d vs. 61.5 [ 20.7 - 122.7 ] d ; P = 0.02 ) . The gentamicin group had greater improvements in Leicester Cough Question naire ( 81.4 % vs. 20 % ; P < 0.01 ) and St. George 's Respiratory Question naire ( 87.5 % vs. 19.2 % ; P < 0.004 ) score . No differences were seen in 24-hour sputum volume , FEV(1 ) , FVC , or forced expiratory flow , midexpiratory phase . No P. aeruginosa isolates developed resistance to gentamicin . At follow-up , all outcome measures were similar to baseline . CONCLUSIONS Regular , long-term nebulized gentamicin is of significant benefit in non-cystic fibrosis bronchiectasis but treatment needs to be continuous for its ongoing efficacy . Clinical trial registered with www . clinical trials.gov ( NCT 00749866 ) The airways of cystic fibrosis ( CF ) patients are characterised by neutrophils that release high amounts of elastase overwhelming the local antiprotease shield . Inhalation of α1-antitrypsin ( AAT ) may restore the protease – antiprotease balance and attenuate airway inflammation in CF airways . The aims of the present study were : 1 ) to assess the best deposition region for inhaled AAT by two different inhalation strategies ; and 2 ) to examine the effect of 4 weeks of AAT inhalation on lung function , protease – antiprotease balance and airway inflammation in CF patients . In a prospect i ve , r and omised study , 52 CF patients received a daily deposition by inhalation of 25 mg AAT for 4 weeks targeting their peripheral or bronchial compartment . The levels of elastase activity , AAT , pro-inflammatory cytokines , neutrophils , immunoglobulin G fragments and the numbers of Pseudomonas aeruginosa were assessed in induced sputum before and after the inhalation period . Inhalation of AAT increased AAT levels and decreased the levels of elastase activity , neutrophils , pro-inflammatory cy \n Output:\n " }, { "from": "agent", "value": "In this review sputum NE has proved useful as an inflammatory marker both in stable state bronchiectasis and during exacerbations and local or systemic antibiotic treatment .\nNE has also been associated with risk of exacerbation , time to next exacerbation and all-cause mortality .\nThis study review s also the role of NE as a specific target of treatment in bronchiectasis ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: In a double‐blind trial the effects of a single dose of doxapram ( 1–1.5 mg/kg ) on the postoperative arterial oxygen tension of patients who had undergone surgical fixation of a fractured neck of femur was measured . In contrast to other reports of the effect of a single dose of doxapram , there was no improvement in arterial oxygen tension with respect to the control group . It is reasoned that doxapram may exert its effect by increasing the functional residual capacity in the immediate postoperative period . The central analeptic properties of doxapram may be grossly underestimated Postoperative cognitive dysfunction ( POCD ) has been attributed to long-acting sedatives . We hypothesized that diazepam and its active metabolites could be detected in blood after surgery and correlated with POCD , 1 week after surgery in elderly patients . We studied 35 patients , 60 yr or older , undergoing abdominal surgery with general anaesthesia , including diazepam . Neuropsychological tests were performed before surgery and at discharge , where blood concentrations ( free fraction ) of benzodiazepines were also measured . POCD was found in 17 patients ( 48.6 % ) . Diazepam or desmethyldiazepam was detected in 34 patients ; median postoperative blood concentrations were 0.06 and 0.10 mumol kg-1 , respectively . In a multiple regression analysis considering age , duration of anaesthesia and blood concentrations of diazepam and desmethyldiazepam , only age was found to correlate with the composite z-score ( F test , P < 0.01 ) . The postoperative cognitive dysfunction we found in elderly patients after operation could not be explained by benzodiazepine concentrations detected in blood Spinal block causes paralysis of preganglionic sympathetic fibres , while ketamine induces activation of the sympathetic nervous system . Hypotension is a frequent complication during spinal anaesthesia and is associated with an increased risk of postoperative mortality . The aim of our study was to compare circulatory changes in patients who received either fentanyl or ketamine during spinal anaesthesia . Thirty patients ( ASA I‐III ) scheduled to undergo spinal anaesthesia for osteo synthesis of hip fractures were allocated to receive either ketamine or fentanyl intravenously during the procedure . Immediately before anaesthesia , 7 ml/kg BW of an isotonic NaCl solution was administered i.v . Patients received either fentanyl 1.5 mg/kg BW i.v . before anaesthesia , or ketamine 0.7 mg/kg BW i.v . before anaesthesia , and 0.35 mg/kg BW 15 and 30 min after the first dose . No prophylactic vasopressor was used . During the first 40 min of anaesthesia a fluid load of 14 ml/kg BW was given i.v . If the mean arterial pressure ( MAP ) fell more than 20 % , the infusion rate was increased . If the reduction in MAP exceeded 33 % or if the systolic pressure decreased to less than 80 mmHg , patients were registered as haemodynamically unstable . In both groups the spinal anaesthesia caused a reduction in MAP . The MAP was lower in the fentanyl group than in the ketamine group at all times . In the kentanyl group six subjects developed a haemodynamically unstable condition , while only one subject in the ketamine group was registered as such ( P<0.05 ) . There was no significant change in heart rate in either group . We conclude that during spinal anaesthesia patients can in part be kept haemodynamically stable by intravenous administration of ketamine We have compared the haemodynamic effects of ephedrine alone with ephedrine and colloid for the treatment of hypotension produced by subarachnoid anaesthesia in 30 patients aged 60 - 90 yr with fractures of the neck of femur . Group one received ephedrine as an initial bolus dose of 0.2 mg kg-1 followed by an infusion of 0.5 mg kg-1 h-1 . Group two received ephedrine and colloid ( polygeline , Haemaccel ) 8 ml kg-1 . If necessary , up to three rescue bolus doses of ephedrine ( 0.1 mg kg-1 ) and then colloid solution ( 8 ml kg-1 ) were given to maintain systolic arterial pressure ( SAP ) at > 75 % of baseline . Arterial pressure was measured by automated oscillotonometry , central venous pressure ( CVP ) by a manometer and cardiac index ( CI ) , stroke index ( SI ) and heart rate ( HR ) by transthoracic electrical bioimpedance . Systemic vascular resistance index ( SVRI ) was derived . In patients receiving ephedrine only , SVRI , CVP and SI decreased and HR increased ( P < 0.0001 ) . Five patients in this group required colloid , the effect of which was to restore CVP , increase CI and SI , and decrease HR ( P < 0.02 ) . In patients receiving ephedrine and colloid solution , SVRI decreased and CI , SI and HR increased ( P < 0.0001 ) . Ephedrine was not a potent arterial vasoconstrictor and SAP was maintained mainly by increases in SI and HR One hundred patients presenting for surgical treatment of fractured neck of femur were allocated to receive either spinal ( SAB ) or general ( GA ) anaesthesia . Before operation , the mean PaO2 was 9.04 kPa . There was a significant decrease in PaO2 of 0.68 kPa in GA group at 1 h after operation , while blood-gas values were unchanged in SAB group . Eight patients ( 15.7 % ) in GA group and five patients ( 10.2 % ) in SAB group died within 4 weeks of surgery . The difference was not statistically significant Thirty patients undergoing total hip replacement were r and omly allocated to one of two groups . One group ( n = 14 ) received extradural anaesthesia with 0.5 % bupivacaine with adrenaline continued into the postoperative period ( 24 h ) for pain relief . The other group ( n = 16 ) received general anaesthesia with controlled ventilation , using nitrous oxide in oxygen and fentanyl i.v . Following surgery they received a narcotic analgesic i.m . on dem and . Analysis of fibrinolysis inhibition activity and plasminogen activators revealed a significantly better fibrinolytic function in patients given continuous extradural anaesthesia than in those who received general anaesthesia followed by narcotics in the period after operation . Furthermore , the capacity for activation of factor VIII was significantly lower after operation in the former group Background Perioperative myocardial ischemia occurs in 35 % of unselected elderly patients undergoing hip fracture surgery . Perioperative epidural analgesia may reduce the incidence of adverse cardiac events . Methods The effect of early administration of epidural analgesia during the stressful presurgical period , on preoperative cardiac events was evaluated in a prospect i ve r and omized study in 68 patients with hip fractures who either had known coronary artery disease or were at high risk for coronary artery disease . On admission to the emergency room , patients were assigned to receive a usual care analgesic regimen ( intramuscular meperidine , control group , n = 34 ) or continuous epidural infusion of local anesthetic and opioid ( epidural group , n = 34 ) . Monitoring in the preoperative period included a preoperative history and physical examination , daily assessment of cardiac adverse events , serial electrocardiograms , cardiac enzymes , and pain scores . Results Preoperative adverse cardiac events were significantly more prevalent in the control group compared with the epidural group ( 7 of 34 vs. 0 of 34;P = 0.01 ) . Adverse cardiac events included fatal myocardial infa rct ion in three , fatal congestive heart failure in one , nonfatal congestive heart failure in one , and new onset atrial fibrillation in two . The incidence of intraoperative and postoperative adverse cardiac events was similar for the two groups . The significant difference between groups in the incidence of preoperative cardiac events prompted interruption of the study after the planned interim analysis . Conclusions The authors ’ data indicate that compared with conventional analgesia , early administration of continuous epidural analgesia is associated with a lower incidence of preoperative adverse cardiac events in elderly patients with hip fracture who have or are at risk for coronary artery disease . Preoperative epidural analgesia may be advantageous for this surgical population Fifty-five patients presenting with fractured neck of femur were r and omly allocated to either a st and ard general anaesthetic or spinal block in the lateral position combined with light sedation . The comparability of the two groups was established . There was little difference in the intra-operative course of postoperative morbidity in the two groups . There was a statistically significant difference in post-operative mortality between two groups , the general anaesthetic group showing a much higher mortality than the spinal group Forty elderly patients ( mean age 78.9 years ) undergoing acute surgery for hip fracture were given at r and om either spinal analgesia with bupivacaine 0.75 % or general anaesthesia with diazepam , fentanly and N2O/O2 . Mental function was studied pre‐operatively with an abbreviated mental test and 1 week and 3 months postoperatively in both groups . Mortality and number of complications was similar in the two groups , but a shorter time of ambulation was seen in the spinal group compared to the general anaesthetic group . No persistent impairment in mental function was found after acute hip surgery under spinal or general anaesthesia and the only advantage of regional technique was a shorter time of ambulation The aim of this study was to compare hypobaric solutions of tetracaine and bupivacaine in 30 geriatric patients undergoing surgical repair of hip fractures while under continuous spinal anesthesia . Tetracaine 1 % and bupivacaine 0.5 % were mixed with distilled water to prepare hypobaric 0.25 % solutions . In a double-blind fashion , all patients received 3 ml ( 7.5 mg ) of either solution in the lateral decubitus position with the operated side up , the table being kept horizontal for 30 minutes after injection . The mean highest sensory levels in both groups , and in both operated and non-operated sides in the same group , were comparable , ranging between T7 and T8.5 . Duration of analgesia was 134 minutes with tetracaine and 130 minutes with bupivacaine ( NS ) . In both groups , motor blockade was satisfactory in 29/30 patients on the operated side . The frequency of a decrease in systolic blood pressure of more than 30 % was similar in the two groups . The authors conclude that hypopobaric solutions of both tetracaine and bupivacaine are suitable for surgical repair of hip fractures in geriatric patients and produce comparable anesthetic and hemodynamic effects BACKGROUND AND OBJECTIVES This prospect i ve r and omized study was design ed to determine the hemodynamic effects and quality of combined lumbar and sacral plexus block compared with plain bupivacaine spinal anesthesia in the elderly for repair of proximal femoral fractures . METHODS Twenty-nine elderly patients ranging in age from 68 to 97 years were r and omly assigned to 2 groups : a spinal anesthesia group with single-shot 3 mL 0.5 % plain bupivacaine , and a combined block group with 30 mL lidocaine 1.33 % with epinephrine for the posterior lumbar plexus block and 10 mL same mixture for the parasacral block and an iliac crest block with 5 mL lidocaine 1 % . RESULTS No need for general anesthesia was encountered in either group . Anesthesia was judged unsatisfactory in 1 of 15 patients in the combined block group . The initial decrease of mean arterial pressure was 38 % in the spinal group and 27 % in the block group and was not significantly different . A more prolonged hemodynamic effect was found in the spinal group , indicated by the more frequent use of ephedrine to stabilize blood pressure ( P<.05 ) . Patients over 85 years had a significantly larger decrease in blood pressure than younger patients ( P<.01 ) . CONCLUSIONS Plain bupivacaine spinal anesthesia and combined lumbar/sacral plexus block provided adequate anesthesia for repair of hip fracture in the elderly . Hypotension was induced by both the combined peripheral nerve block and plain bupivacaine spinal anesthesia in aged patients ; hypotension was found to be longer lasting after spinal anesthesia and of a larger magnitude in patients over 85 years of age During a prospect i ve r and omized trial , 50 geriatric patients underwent surgery for a fractured femoral neck . The perioperative circulatory and respiratory effects of anesthesia with enflurane or balanced anesthesia with enflurane and fentanyl were compared . We were particularly looking for postoperative respiratory depression after a st and ard dose of fentanyl given during balanced anesthesia . Method . In 25 patients anesthesia was induced with 0.2 mg/kg etomi date and 1 mg/kg succinylcholine and maintained with 0.15 mg/kg alcuronium and enflurane . Twenty-five patients received a additional dose of 5 micrograms/kg \n Output:\n " }, { "from": "agent", "value": "Regional anaesthesia may reduce acute postoperative confusion but no conclusions can be drawn for mortality or other outcomes" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: We performed a r and omized , prospect i ve clinical trial comparing intratracheal administration of human surfactant with conventional treatment with intermittent m and atory mechanical ventilation alone for treatment of severe respiratory distress syndrome in preterm infants of less than 30 weeks gestation . Twenty-two infants ( mean gestational age 27.0 weeks , mean birth weight 987 gm ) were given surfactant , and 23 infants ( mean gestational age 27.2 week , mean birth weight 1055 gm ) received intermittent m and atory ventilation . Infants given surfactant required less FiO2 during the first week , had lower mean airway pressure during the first 48 hours , and had improved ventilatory index and a/A PO2 ratio . Death or the occurrence of bronchopulmonary dysplasia was significantly less among infants given surfactant ( P = 0.019 ) . Pneumothorax , pulmonary interstitial emphysema , and need for FiO2 greater than or equal to 0.3 for greater than 30 days was significantly less in the surfactant group . This trial confirms the efficacy of treatment with human surfactant in preterm infants with severe respiratory distress syndrome We carried out a multicenter r and omized , placebo-controlled trial to evaluate the efficacy and safety of surfactant in the treatment of respiratory distress syndrome . The study population was made up of newborn infants weighing 750 to 1750 g who were receiving assisted ventilation with 40 percent or more oxygen . The eligible infants received a single dose of either surfactant ( 100 mg of phospholipid per kilogram of body weight [ 4 ml per kilogram ] ) or an air placebo ( 4 ml per kilogram ) , administered into the trachea within eight hours of birth by an investigator not involved in the clinical care of the infant . When compared with the infants who received the placebo ( n = 81 ) , the infants who were treated with surfactant ( n = 78 ) had a 0.12 greater average increase in the ratio of arterial to alveolar oxygen tension ( P less than 0.0001 ) , a 0.20 greater average decrease in the fractional inspiratory oxygen concentration ( P less than 0.0001 ) , and a 0.26-kPa greater average decrease in the mean airway pressure ( P less than 0.0001 ) during the 72 hours after treatment . Pneumothorax was less frequent among the infants treated with surfactant than in the control group ( 13 percent vs. 37 percent ; P = 0.0005 ) . There were no statistically significant differences between the groups in the proportion of infants in each of five ordered clinical -status categories on day 7 ( P = 0.08 ) or day 28 ( P = 0.75 ) after treatment . There were also no significant differences between the groups in the frequency of bronchopulmonary dysplasia , patent ductus arteriosus , necrotizing enterocolitis , or periventricular-intraventricular hemorrhage . In each group , 17 percent of the infants died by day 28 . We conclude that treatment with the single-dose surfactant regimen used in this study reduces the severity of respiratory distress during the 72 hours after treatment and decreases the frequency of pneumothorax , but that it does not significantly improve clinical status later in the neonatal period and does not reduce neonatal mortality . Further study of different surfactant regimens and patient- selection criteria will be required to determine whether this initial improvement can be translated into reductions in mortality or serious morbidity In a double-blind clinical trial the effects of a single dose of reconstituted bovine surfactant ( ' Surfactant TA ' ) were assessed in 30 premature infants ( birthweight 751 - 1750 g ) with severe hyaline membrane disease . 17 infants had a sonicated saline suspension of 100 mg/kg surfactant phospholipid instilled into the trachea at 5.0 ( SD 0.7 ) hours of age and 13 infants received saline by the same route at 4.3 ( 1.1 ) hours of age . In the surfactant-treated group there was early improvement in oxygenation and ventilation . Haemodynamically significant patent ductus arteriosus occurred more often in the surfactant group ; pneumothorax and pulmonary interstitial emphysema occurred less often . The combined incidence of death and severe bronchopulmonary dysplasia was significantly lower in the surfactant group ( 3/17 ) than in the placebo group ( 9/13 ) The postnatal growth , respiratory status and neurodevelopmental outcome of surviving babies enrolled in the first European multicentre trial of porcine surfactant ( Curosurf ) replacement for severe neonatal respiratory distress syndrome , were assessed at corrected ages of 1 and 2 years . Follow up rates of survivors were 93 % at 1 year and 89 % at 2 years . Treated and control groups were similar at both 1 and 2 years in terms of physical growth , the prevalence of persistent respiratory symptoms and the occurrence of major and minor disability . Serum antibodies recognising Curosurf and surfactant-anti-surfactant immune complexes were detected in both treated and control babies , the titres showing no difference between groups . Examination of histological lung sections from non-survivors revealed a higher incidence of severe pulmonary interstitial emphysema in control babies than in those treated with surfactant . Surfactant treatment for severe respiratory distress syndrome reduces neonatal mortality and air leaks and is not associated with an increase in disability 2 years later Treatment with bovine surfactant ( SF-RI 1 ) was shown to be efficacious in improving pulmonary function and in increasing survival rate without BPD in very premature infants . Surfactant therapy did not affect the risk of major complications of prematurity We conducted a prospect i ve , r and omized , unblinded , controlled trial of exogenous bovine surfactant ( surfactant TA ) in premature infants requiring ventilator support for the treatment of severe hyaline membrane disease . Forty-one low birth weight infants with severe hyaline membrane disease were r and omly assigned to saline or surfactant therapy and treated within eight hours of birth . Significant improvements in oxygenation ( increased arterial/alveolar PO2 ) and respiratory support ( decreased mean airway pressure ) were seen in the group receiving surfactant within four hours after treatment . These improvements were maintained in the surfactant-treated infants , who also had fewer pneumothoraces and fewer number of days in environments of fractional inspiratory oxygen greater than 0.4 mm Hg . No problems were associated with administration of surfactant , and no acute side effects were detected . We conclude that exogenous surfactant , administered early in the course of severe hyaline membrane disease , is an effective therapy that can diminish the amount of respiratory support required during the first 48 hours of life The results obtained with porcine surfactant ( Curosurf ) administration for the treatment of hyaline membrane disease ( HMD ) are reported . Thirty premature infants weighing 700 to 2,000 g with severe HMD ( mechanical ventilation and oxygen requirement ( FiO2 ) greater than 60 % were r and omly allocated at 2 to 15 hours postnatal age . Eight of the 30 patients included in this group participated in a multicenter european trial . The fifteen infants with mean gestational age ( GA ) of 29.5 weeks included in the treatment group ( T ) , were treated at 8.6 hours of life with a single dose of 200 mg/kg Curosurf given intratracheally while 15 infants of mean GA 30 weeks formed the control group ( C ) . Infants in the T group showed an immediate , dramatic and sustained improvement of oxygenation as reflected by increased PaO2/FiO2 and arterial to alveolar PO2 ratios within 1 hour . This significant improvement in favor of T group ( p less than 0.005 ) persisted for 2 days when control infants began to recover . This improvement in oxygenation allowed a significant decrease of FiO2 ( p less than 0.005 ) and mean airway pressure ( p less than 0.01 ) in the T group within 1 hour and up till the second day . Despite this early improvement obtained with Curosurf the survival rate at 28 days of life and the incidence of associated HMD complications were not significantly modified . However the tendency was towards decreased respiratory morbidity . The discussion will consider the value of multiple doses We investigated the clinical efficacy of a new surfactant product , Curosurf , isolated from porcine lungs by liquid-gel chromatography . Ten premature newborn infants ( birth weight 850 - 1850 g ) , all ventilated artificially for severe hyaline membrane disease categorized radiologically as stage III-IV , received a single dose of Curosurf ( 200 mg/kg ) via the tracheal tube . This treatment result ed in a rapid improvement of oxygenation , similar to that observed by other teams collaborating in the study and , in an astonishingly fast resolution of the radiological changes . In comparison with a control group of 8 infants , the surfactant-treated babies also had a lower incidence of acute and chronic complications In a r and omized , controlled study , human surfactant derived from amniotic fluid was administered within 12 hours of birth to infants with severe respiratory distress syndrome who were born at 24 to 32 weeks of gestation weighing less than or equal to 1500 gm . A second dose of surfactant was given to patients in the treatment group if they met ventilator requirements indicating relapse or lack of response to the initial dose . No significant improvement was observed in mortality rate ( 9/28 vs 15/31 ) or incidence of bronchopulmonary dysplasia ( 5/28 vs 3/31 ) when surfactant-treated infants were compared with control subjects , although there was a significant reduction in initial respirator and inspired oxygen requirements and the arterial/alveolar oxygen ratio improved . In addition , there was a significant reduction in pulmonary air leak in treated infants ( 10/28 vs 20/31 ; p less than 0.05 ) . Retreatment was associated with an attenuated ventilatory response and with a higher mortality rate ( 7/14 ) than that of infants who did not require a second dose ( 2/14 ; p = 0.05 ) , indicating a more severe form of disease . Multiple discriminant analysis , including eight independent variables , revealed that increasing birth weight , earlier age at surfactant treatment , and female gender were significantly associated with survival . These data suggest that early surfactant treatment may reduce mortality rates in very low birth weight infants with severe respiratory distress syndrome , as well as reduce ventilator requirements and the incidence of pulmonary air leaks To determine if outcomes of low birth weight neonates with respiratory distress syndrome can be improved by the administration of multiple doses of bovine surfactant , we conducted two identical multicenter , controlled trials , and the results were combined for analysis . Seven hundred and ninety-eight neonates weighing 600 to 1750 g at birth who had developed respiratory distress syndrome within 6 hours of birth were assigned r and omly to receive either 100 mg of phospholipid/kg of Survanta , a modified bovine surfactant ( n = 402 ) , or a sham dosing procedure ( n = 396 ) . Neonates whose respiratory distress persisted could be given up to three more doses , with all doses to be given in the first 48 hours after birth . Dosing was performed by investigators not involved in the clinical care of the neonates ; nursery staff were kept blinded as to the treatment assignment . Fewer Survanta-treated neonates died of any cause ( 18.4 % vs 27.3 % , P = .002 ) , died of respiratory distress syndrome ( 9.0 % vs 20.3 % , P less than .001 ) , and either died or developed bronchopulmonary dysplasia due to respiratory distress syndrome ( 51.2 % vs 64.6 % , P less than .001 ) . Neonates who received Survanta also had greater improvement in their oxygenation and ventilatory status from baseline to 72 hours than did control neonates . Survanta-treated neonates were at lowered risk for developing pulmonary interstitial emphysema ( 18.6 % vs 39.3 % , P less than .001 ) and other pulmonary air leaks ( 11.5 % vs 25.9 % , P less than .001 ) . We conclude that multiple doses of Survanta given after diagnosis of respiratory distress syndrome reduce mortality and morbidity We assessed postnatal growth , neurodevelopmental outcome , and occurrence of respiratory illnesses in 46 infants of very low birth weight who were enrolled in a r and omized , controlled , bicenter clinical trial of human surfactant treatment for respiratory distress syndrome . No long-term adverse effects of human surfactant treatment were detected between control and human surfactant-treated infants with respect to growth , neurologic , or developmental outcome . Infants with chronic lung disease , regardless of treatment group , had poorer growth and were more likely to have neurodevelopmental abnormalities at 12 to 24 months of age Several r and omized clinical trials have shown that surfactant therapy improves the pulmonary status of infants with respiratory distress syndrome and has the potential to reduce morbidity and mortality in these infants . Relatively little is known , however , about the long-term consequences of surfactant treatment . In this report , the results of health and developmental assess \n Output:\n " }, { "from": "agent", "value": "The studies demonstrated an initial improvement in respiratory status ( improved oxygenation and decreased need for ventilator support ) .\nAUTHORS ' CONCLUSIONS Infants with established respiratory distress syndrome who receive animal derived surfactant extract treatment have a decreased risk of pneumothorax , a decreased risk of pulmonary interstitial emphysema , a decreased risk of mortality , and a decreased risk of bronchopulmonary dysplasia or death" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: PURPOSE To evaluate the safety and efficacy of intravenous ( IV ) sodium ferric gluconate complex ( FG ) , oral ferrous sulfate , or no iron to increase hemoglobin ( Hb ) in anemic cancer patients receiving chemotherapy and epoetin alfa . PATIENTS AND METHODS In this open-label , multicenter trial , 187 patients with chemotherapy-related anemia ( Hb < 11 g/dl ; serum ferritin > or = 100 ng/ml or transferrin saturation > or = 15 % ) scheduled to receive chemotherapy and epoetin alfa ( 40,000 U subcutaneously weekly ) were r and omized to 8 weeks of 125 mg of IV FG weekly , 325 mg of oral ferrous sulfate three times daily , or no iron . The primary outcome was a change in Hb from baseline to endpoint , first whole-blood or red blood cell transfusion , or study withdrawal . RESULTS One hundred twenty-nine patients were evaluable for efficacy ( FG , n = 41 ; oral iron , n = 44 ; no iron , n = 44 ) . Mean increase in Hb was 2.4 g/dl ( 95 % confidence interval [ CI ] , 2.1 - 2.7 ) for FG ( p = .0092 vs. oral iron ; p = .0044 vs. no iron ) , 1.6 g/dl ( 95 % CI , 1.1 - 2.1 ) for oral iron ( p = .7695 vs. no iron ) , and 1.5 g/dl ( 95 % CI , 1.1 - 1.9 ) for no iron . Hb response ( increase > or = 2 g/dl ) was 73 % for FG ( p = .0099 vs. oral iron ; p = .0029 vs. no iron ) , 46 % for oral iron ( p = .6687 vs. no iron ) , and 41 % for no iron . FG was well tolerated . CONCLUSION For cancer patients with chemotherapy-related anemia receiving epoetin alfa , FG produces a significantly greater increase in Hb and Hb response compared with oral iron or no iron , supporting more aggressive treatment with IV iron supplementation for these patients Hepatic sinusoidal obstruction syndrome ( SOS ) is a serious complication in hematopoietic stem cell transplant ( HSCT ) recipients . To determine the impact of pretransplantation hyperferritinemia on the risk of SOS after HSC transplantation , we retrospectively studied 427 HSCT recipients ( 179 autologous and 248 allogeneic ) . Serum ferritin levels were measured before transplantation . Patients with and without a diagnosis of SOS were compared regarding demographics ; underlying disease ; transplant characteristics ; receipt of imatinib , busulfan , total body irradiation , gemtuzumab , vancomycin , acyclovir , or methotrexate ; and baseline serum ferritin . Univariate and multivariate ( stepwise logistic regression ) analyses were performed . SOS was diagnosed in 88 patients ( 21 % ) at a median of 10 days ( range , 2 - 29 days ) after transplantation . By multivariate analysis , allogeneic HSC transplantation ( odds ratio [ OR ] = 8.25 ; 95 % confidence interval [ 95 % CI ] , 3.31 - 20.57 ) , receipt of imatinib ( OR = 2.60 ; 95 % CI , 1.16 - 5.84 ) , receipt of busulfan ( OR = 2.18 ; 95 % CI , 1.25 - 3.80 ) , and ferritin serum level higher than 1000 ng/dL ( OR = 1.78 ; 95 % CI , 1.02 - 3.08 ) were risk factors for SOS . A ferritin serum level higher than 1000 ng/dL in the pretransplantation period is an independent risk factor for SOS . The results suggest the need for prospect i ve studies addressing the use of iron chelation in the pretransplantation period Ninety one patients between the ages of 17 and 58 years undergoing histocompatible allogeneic transplants from sibling donors were entered into a double-blind r and omised trial to evaluate the effect of human erythropoietin ( rhu EPO ) at a dose of 300 units per kg/day given thrice weekly by intravenous injection on erythropoiesis and on erythrocyte and platelet transfusion requirements . Dose was ceased when the haemoglobin exceeded 12g/dL and recommenced if the haemoglobin fell below 12 g/dL , at 150 units/kg/day . If the haemoglobin exceeded 12 g/dL on a further occasion , the dose of rhu EPO was not given . Patients received two units of erythrocytes when the haemoglobin dropped below 8.5g/dL and received platelet transfusions when the count dropped below 20 x 10(9)/L. Univariate analysis revealed a significantly higher reticulocyte count , haemoglobin concentration and bone marrow erythropoiesis after day 14 in the group receiving rhu EPO but this was not reflected in decreased erythrocyte transfusion ( 7 + /- 5 in controls versus 6 + /- 5 in rhu EPO group ) or in platelet transfusions ( 11 + /- 7 in controls versus 11 + /- 9 in rhu EPO group ) . Hospitalisation in each group was the same ( 29 + /- 8 in the control group and 28 + /- 8 in the rhu EPO group ) . However , in the multivariate analysis , the administration of rhu EPO was associated with an 18 % reduction in erythrocyte transfusion requirement when other variables were taken into account . No side-effects due to rhu EPO were detected in this study . ( ABSTRACT TRUNCATED AT 250 WORDS Cancer-related anaemia is associated with a wide spectrum of symptoms that can negatively affect quality of life . Because epoetin alfa has demonstrated efficacy in correcting cancer-related anaemia , the impact of this treatment on quality of life was evaluated in a multinational , r and omised , double-blind , placebo-controlled trial in 375 anaemic cancer patients receiving non-platinum-based chemotherapy . The cancer-specific measures of quality of life included the general scale ( FACT-G Total ) and fatigue subscale ( FACT-An Fatigue subscale ) of the Functional Assessment of Cancer Therapy-Anaemia and the Cancer Linear Analogue Scales measuring energy , ability to do daily activities , and overall quality of life . These measures were also used to examine the relationship between haemoglobin levels and quality of life . Both univariate and multiple linear regression analyses of quality of life data were performed . Results of the univariate analysis have been reported previously . The a priori-planned multiple linear regression analysis , which accounted for the effects of disease progression and several other possibly confounding variables on quality of life , showed a significant advantage for epoetin alfa over placebo for the five scales ( all , P<0.05 ) , and confirmed the results of the univariate analysis . For cancer-specific measures , significant correlations were demonstrated between baseline haemoglobin and quality of life ( r , range : 0.14–0.26 , all P<0.05 ) and between change in haemoglobin and change in quality of life ( r , range : 0.26–0.34 , all P<0.01 ) . These findings provide evidence that increasing haemoglobin levels by epoetin alfa administration can significantly improve cancer patients ' quality of life We conducted a prospect i ve r and omized trial to assess hemoglobin ( Hb ) response to recombinant human erythropoietin ( rhEPO ) therapy after hematopoietic cell transplantation ( HCT ) . Patients ( N = 131 ) were r and omized ( 1:1 ) between no treatment ( control arm ) or erythropoietin at 500 U/kg per week ( EPO arm ) . Patients were also stratified into 3 cohorts : patients undergoing myeloablative HCT with rhEPO to start on day (D)28 , patients given nonmyeloablative HCT ( NMHCT ) with rhEPO to start on D28 , and patients also given NMHCT but with rhEPO to start on D0 . The proportion of complete correctors ( ie , Hb ≥13 g/dL ) before D126 posttransplant was 8.1 % in the control arm ( median not reached ) and 63.1 % in the EPO arm ( median , 90 days ) ( P < .001 ) . Hb levels were higher and transfusion requirements decreased ( P < .001 ) in the EPO arm , but not during the first month in the nonmyeloablative cohort starting rhEPO on D0 . There was no difference in rates of thromboembolic events or other complications between the 2 arms . This is the first r and omized trial to demonstrate that rhEPO therapy hastens erythroid recovery and decreases transfusion requirements when started one month after allogeneic HCT . There was no benefit to start rhEPO earlier after NMHCT For the majority of patients with iron deficiency anemia ( IDA ) , a full course of intravenous ( IV ) iron is 1 g. Most IV irons require 5–10 administrations of 100–300 mg . We have successfully employed 1 g low molecular weight iron dextran over 1 hr . For further convenience for patients and physicians , we explored the administration of 1.02 g of ferumoxytol over 15 min instead of the approved 2 × 510 mg injections . Sixty patients with IDA , ( hemoglobin < 11 g/dL , transferrin saturation [ TSAT ] ≤20 % , and ferritin < 100 ng/mL ) with an inadequate response or intolerance to oral iron , received 1020 mg ferumoxytol over 15 min . Vital signs were measured for 1 hr . Adverse events ( AEs ) were collected via telephone at 1 , 2 , and 7 days . Follow‐up visits occurred at 4 and 8 weeks for efficacy assessment s. The primary endpoint was safety and tolerability . Secondary efficacy endpoints included mean change in hemoglobin , TSAT , and red cell distribution width . No serious adverse events ( SAEs ) occurred . Fifty‐eight patients received the planned dose . Twenty‐six out of sixty ( 43.3 % ) patients reported AEs of which 13 were mild and transient during infusion . All resolved within minutes . Fourteen patients reported self‐limited arthralgias , myalgias , and /or headache within 24–48 hr . At Baseline , the mean hemoglobin was 9.4 g/dL. The mean increments at Week 4 and 8 were 2.1 and 2.6 g/dL , respectively . Ferumoxytol , administered as 1.02 g infusion over 15 min was well tolerated with no SAEs and demonstrated excellent efficacy . If corroborated in future studies this represents an improved method of treating IDA . Am . J. Heamtol . 88:944–947 , 2013 . © 2013 Wiley Periodicals , We have used recombinant human erythropoietin ( rHuEPO ) in a phase I/II clinical trial to evaluate its ability to reverse refractory anemia in hematologic disorders . rHuEPO was administered subcutaneously 5 days per week at escalating doses ( 50 to 150 U/kg per day ) . The aim of treatment was a hemoglobin ( Hb ) level greater than or equal to 10 g/dL without blood transfusion . Of 25 patients treated , 17 were evaluable , most of them with a regular need for transfusion . Eight of these had lymphoproliferative disorders ( three cases of malignant lymphoma and five of monoclonal gammopathy ) and were exposed to cytotoxic therapy . The other nine patients had hematopoietic stem cell disorders ( four cases of myelodysplastic syndrome , three of idiopathic myelofibrosis , and two of chronic myelogenous leukemia ) . All patients with lymphoproliferative disorder had serum EPO levels inappropriately low for the degree of anemia , while patients with stem cell disorder showed variable values . Erythroid marrow activity was inadequate in all cases . Seven of eight patients with lymphoproliferative disorder responded to treatment maintaining Hb above 10 g/dL without transfusion . The median dose of rHuEPO required for correction of anemia was 75 U/kg . In four cases response was maintained with 50 U/kg , three times per week . There was no complete response among patients with hematopoietic stem cell disorder , although transfusion requirement was eliminated or reduced in four cases . Four patients developed functional iron deficiency during rHuEPO treatment and required iron supplementation to obtain response . Aggravation of splenomegaly was observed in two cases of myeloproliferative disorder . We conclude that : ( 1 ) subcutaneous administration of rHuEPO can be effective and safe in patients with lymphoproliferative disorder exposed to chemotherapy and showing inappropriate EPO response to anemia ; ( 2 ) this is less likely in hematopoietic stem cell disorders , although favorable responses may be observed in occasional patients ; and ( 3 ) functional iron deficiency as a cause of nonresponse to rHuEPO is frequent also in nonrenal anemia Pre‐ clinical studies have demonstrated \n Output:\n " }, { "from": "agent", "value": "Nevertheless , the more robust and intriguing of these data suggest that the ESA 's administration at an appropriate time after the infusion of stem cells may be effective both in autologous and allogeneic HSCTs ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Background Progressive cell-mediated immunodeficiency with decrease of CD4 + lymphocyte count to less than or equal to 200 cells/mm3 is a major risk factor for colonization with C and ida species and development of c and idiasis . Oropharyngeal c and idiasis may occur in up to 90 % of human immunodeficiency virus (HIV)-infected patients during the course of the disease . This study is to determine the effect of prolonged highly active antiretroviral therapy ( HAART ) on oropharyngeal colonization with C and ida species and oral c and idiasis . Methods A prospect i ve , longitudinal follow-up study in HIV-infected patients receiving HAART . Results The mean CD4 + count increased from 232.5 to 316 cells/mm3 and the proportion of patients whose CD4 + count less than 200 cells/mm3 decreased from 50.0 % to 28.9 % ( p = 0.0003 ) in patients receiving HAART for at least 2 years . The prevalence of oral c and idiasis decreased from 10.6 % to 2.1 % ( p = 0.004 ) . The decrease in C and ida colonization was less impressive , falling from 57.8 % to 46.5 % ( p = 0.06 ) . Of the 142 patients enrolled in at least two surveys , 48 ( 33.8 % ) remained colonized with C and ida and 42 ( 29.6 % ) remained negative . In the remaining 52 patients , 34 switched from culture positive to negative , and an increase in CD4 + lymphocytes was noted in 91.2 % of them . Among the 18 patients who switched from culture negative to positive , 61.1 % also demonstrated an increase in CD4 + lymphocyte count ( p = 0.01 ) . Conclusion These findings indicate that HAART is highly effective in decreasing oral c and idiasis in association with a rise in CD4 + lymphocyte counts , but only marginally effective in eliminating C and ida from the oropharynx Objective : To evaluate the efficacy of itraconazole cyclodextrin solution in fluconazole-refractory oropharyngeal c and idiasis ( OPC ) , and to correlate clinical outcome with in vitro susceptibility and serum azole levels . Design : A prospect i ve , open-label , intervention study . Setting : A university hospital , which serves as the provincial HIV referral center . Patients and interventions : Thirty-six HIV-infected individuals referred for fluconazole-refractory OPC were evaluated prospect ively between May 1993 and March 1995 , including clinical assessment , serum azole levels , and susceptibility testing of C and ida spp . isolates . Itraconazole solution was administered orally at a daily dose of 200 mg for 14 days , followed by suppressive therapy . Thirty-four patients were evaluable . Main outcome measure : Resolution of oral pseudomembranous lesions . Results : Initial isolates were C and ida albicans ( n = 33 ) , C. glabrata ( n = 1 ) , C. krusei ( n = 1 ) , and mixed infection with C. albicans and C. krusei ( n = 1 ) . Fluconazole serum levels obtained at the time of failed therapy ranged from 4.7 to 40 mg/l ( median , 12.9 mg/l ) . Itraconazole was generally well tolerated . Clinical responses were observed in 65 % ( 22 out of 34 ) of evaluable cases . Among the responders , relapse had occurred within 2 months for four ( 36 % ) out of 11 cases who continued with follow-up . The median fluconazole minimal inhibitory concentration ( MIC ) was 64 mg/l for isolates from fluconazole-refractory cases , compared with a median of 0.5 mg/l for control isolates ( P = 0.002 ) . The median itraconazole MIC for isolates from fluconazole-refractory cases was 1.25 mg/l , compared with a median of 0.078 mg/l for controls ( P = 0.011 ) . Conclusion : A correlation between clinical response and in vitro susceptibility was clearly demonstrated for fluconazole , but not for itraconazole . Itraconazole cyclodextrin solution may be effective for fluconazole-refractory OPC and should be considered prior to salvage therapy with intravenous amphotericin OBJECTIVES --To compare the tolerance , efficacy , and pharmacokinetics of amphotericin deoxycholate ( Fungizone ) prepared in a parenteral fat emulsion ( Intralipid 20 % ) or glucose in HIV patients with c and idiasis . DESIGN --Non-blind r and omised controlled trial . SETTING --University hospital ; tertiary clinical care . PATIENTS --22 HIV positive patients with oral c and idiasis . INTERVENTIONS --Amphotericin 1 mg/kg/day given on four consecutive days as a one hour infusion dissolved in either 5 % glucose ( amphotericin-glucose ) or parenteral fat emulsion at a final concentration of 2 g/l fat emulsion ( amphotericin-fat emulsion ) . MAIN OUTCOME MEASURES -- Clinical tolerance ( fever , chills , sweats , nausea , arterial pressure , and pulse rate ) ; biological tolerance ( serum creatinine , electrolyte , and magnesium values ) ; clinical score of c and idiasis ; and serum concentrations of amphotericin . RESULTS --11 patients were enrolled in each group . All the amphotericin-fat emulsion infusions were given without serious problem whereas four amphotericin-glucose infusions were stopped because of renal impairment ( n = 3 ) or severe chills ( n = 2 ) , or both . For patients completing the amphotericin-glucose treatment creatine concentration increased by 42 mumol/l ; four of seven patients had at least one creatinine value > or = 133 mumol/l versus one of 11 receiving amphotericin-fat emulsion . Magnesium concentration fell significantly with amphotericin-glucose but not with amphotericin-fat emulsion . Clinical side effects were noted in 36/38 infusions with amphotericin-glucose but 10/44 with amphotericin-fat emulsion . Oral c and idiasis score was reduced similarly in both groups . Serum amphotericin concentrations were significantly lower and the volume of distribution of the drug higher after infusion of amphotericin-fat emulsion than after amphotericin-glucose . CONCLUSIONS -- Clinical and renal toxicity of amphotericin are reduced when the drug is prepared in fat emulsion . Preparation is simple and cost effective . Its efficacy is similar to that of conventional amphotericin In an open multicentre study the efficacy and safety of fluconazole versus ketoconazole were evaluated in the treatment of 46 pediatric patients with oropharyngeal c and idiasis and AIDS or HIV infection . Twenty-four subjects received oral fluconazole in a dosage of 3 mg/kg/day and 22 subjects received oral ketoconazole in a dosage of 7 mg/kg/day . The treatment duration ranged from 5 to 49 days . Results showed that fluconazole and ketoconazole have comparable efficacy and safety in the treatment of oropharyngeal c and idiasis in HIV-infected children . Patients treated with fluconazole had higher clinical and mycological cure rates at the end of therapy ( 88 % and 71 % respectively ) than those treated with ketoconazole ( 81 % and 57 % respectively ) . One case of drug-related side effects ( diarrhea and abdominal pain ) in a patient receiving ketoconazole result ed in discontinuation of treatment . Follow-up examinations 2 and 4 weeks post-treatment showed a comparably high rate of relapse in both patient groups BACKGROUND We evaluated the efficacy and safety of oral posaconazole for human immunodeficiency virus (HIV)-infected subjects with oropharyngeal c and idiasis ( OPC ) and /or esophageal c and idiasis ( EC ) who were clinical ly refractory to treatment with oral fluconazole or itraconazole . METHODS Subjects with confirmed OPC or EC who did not improve after receiving st and ard courses of fluconazole or itraconazole treatment were eligible for study enrollment . Subjects received either oral posaconazole ( 400 mg twice daily ) for 3 days followed by oral posaconazole ( 400 mg once daily ) for 25 days ( regimen A ; 103 patients ) or oral posaconazole ( 400 mg twice daily ) for 28 days ( regimen B ; 96 patients ) . The primary end point was cure or improvement after 28 days . Primary efficacy analyses were performed on the subset of treated subjects with refractory disease ( e.g. , baseline culture positive for fluconazole- or itraconazole-resistant C and ida species or persistent or progressive clinical signs or symptoms consistent with treatment failure ) . RESULTS Of the modified intent-to-treat population , 132 ( 75 % ) of 176 subjects achieved a clinical response to posaconazole treatment . Clinical response rates were similar between regimen A recipients ( 75.3 % ) and regimen B recipients ( 74.7 % ) . Clinical responses occurred in 67 ( 73 % ) of 92 subjects with baseline isolates resistant to fluconazole , 49 ( 74 % ) of 66 subjects with baseline isolates resistant to itraconazole , and 42 ( 74 % ) of 57 subjects with isolates resistant to both . Clinical response was achieved in 32 ( 74.4 % ) of 43 subjects with endoscopically documented EC . The most common treatment-related adverse events were diarrhea ( 11 % ) , neutropenia ( 7 % ) , flatulence ( 6 % ) , and nausea ( 6 % ) . Eight subjects ( 4 % ) discontinued therapy as a result of a treatment-related adverse event . CONCLUSIONS Posaconazole offers a safe and effective treatment option for HIV-infected subjects with azole-refractory OPC and /or EC CONTEXT Multiple options are now available for prophylaxis of opportunistic infections related to the acquired immunodeficiency syndrome ( AIDS ) . However , because of differences in incidence rates as well as drug efficacy , toxicity , and costs , the role of different types of prophylaxis remains uncertain . OBJECTIVE To determine the clinical impact , cost , and cost-effectiveness of strategies for preventing opportunistic infections in patients with advanced human immunodeficiency virus ( HIV ) disease . DESIGN We developed a Markov simulation model to compare different strategies for prophylaxis of Pneumocystis carinii pneumonia ( PCP ) , toxoplasmosis , Mycobacterium avium complex ( MAC ) infection , fungal infections , and cytomegalovirus ( CMV ) disease in HIV-infected patients . Data for the model were derived from the Multicenter AIDS Cohort Study , r and omized controlled trials , and the national AIDS Cost and Services Utilization Survey . MAIN OUTCOME MEASURES Projected life expectancy , quality -adjusted life expectancy , total lifetime direct medical costs , and cost-effectiveness in dollars per quality -adjusted life-year ( QALY ) saved . RESULTS For patients with CD4 cell counts of 0.200 to 0.300 x 10(9)/L ( 200 - 300/microL ) who receive no prophylaxis , we projected a quality -adjusted life expectancy of 39.08 months and average total lifetime costs of $ 40288 . Prophylaxis for PCP and toxoplasmosis with trimethoprim-sulfamethoxazole for patients with CD4 cell counts of 0.200 x 10(9)/L ( 200/microL ) or less increased quality -adjusted life expectancy to 42.56 months , implying an incremental cost of $ 16000 per QALY saved . Prophylaxis for MAC for patients with CD4 cell counts of 0.050 x 10(9)/L ( 50/microL ) or less produced smaller gains in quality -adjusted life expectancy ; incremental cost-effectiveness ratios were $ 35000 per QALY saved for azithromycin and $ 74000 per QALY saved for rifabutin . Oral ganciclovir for the prevention of CMV infection was the least cost-effective prophylaxis ( $ 314000 per QALY saved ) . Results were most sensitive to the risk of developing an opportunistic infection , the impact of opportunistic infection history on long-term survival , and the cost of prophylaxis . CONCLUSIONS The cost-effectiveness of prophylaxis against HIV-related opportunistic infections varies widely , but prophylaxis against PCP or toxoplasmosis and against MAC delivers the greatest comparative value . In an era of limited re sources , these results can be used to set priorities and explore new alternatives for improving HIV patient care Over 37 months , we conducted a prospect i ve double-blind , r and omized study in a cohort of 138 HIV-infected patients to \n Output:\n " }, { "from": "agent", "value": "Implication s for practice Due to only one study in children it is not possible to make recommendations for treatment or prevention of OC in children .\nDue to insufficient evidence no conclusion could be made about the effectiveness of clotrimazole , nystatin , amphotericin B , itraconazole or ketoconazole with regard to OC prophylaxis .\nIn comparison to placebo , fluconazole is an effective preventative intervention .\nHowever , the potential for resistant C and ida organisms to develop , as well as the cost of prophylaxis , might impact the feasibility of implementation .\nDirection of findings suggests that ketoconazole , fluconazole , itraconazole and clotrimazole improved the treatment outcomes .\nThere is also a strong need for more research to be done on the treatment and prevention of OC in children as it is reported that OC is the most frequent fungal infection in children and adolescents who are HIV positive ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: To evaluate the role of low-molecular weight heparin ( LMWH ) as an alternative to oral anticoagulants in the prevention of recurrent venous thromboembolism , we compared in a r and omized trial conventional warfarin treatment with a three-month course of enoxaparin 4000 anti-Xa units once a day subcutaneously . 187 patients with symptomatic deep-vein thrombosis ( DVT ) , diagnosed by strain-gauge plethysmography plus D-dimer latex assay and confirmed by venography in most cases , were treated with full-dose subcutaneous heparin for ten days and then r and omized to secondary prophylaxis . During the 3-month treatment period , 6 of the 93 patients who received LMWH ( 6 % ) and 4 of the 94 patients on warfarin ( 4 % ) had symptomatic recurrence of venous thromboembolism confirmed by objective testing ( p = 0.5 ; 95 % confidence interval [ CI ] for the difference , -3 % to 7 % ) . Four patients in the LMWH group had bleeding complications as compared with 12 in the warfarin group ( p = 0.04 ; 95 % CI for the difference , 4 % to 14 % ) . In the 9-month follow-up period , during which 34 patients on warfarin prolonged treatment for other 3 months and 14 up to one year , 10 patients in the enoxaparin group and 4 patients in the warfarin group suffered a documented recurrence of venous thromboembolism . Of these 14 late recurrences , just one occurred in patients with postoperative DVT . After one year there were 16 recurrences ( 17 % ) in the LMWH group and 8 ( 9 % ) in the warfarin group ( p = 0.07 ; 95 % CI for the difference , 1 % to 16 % ) . ( ABSTRACT TRUNCATED AT 250 WORDS The aim of this study was to assess the effectiveness of low-molecular-weight heparin ( LMWH ) treatment of deep vein thrombosis ( DVT ) in terms of the evolution of thrombosis , the incidence of adverse events , and compliance with heparin treatment using 2 types of LMWH available on the market administered in therapeutic doses throughout the period of treatment ( Nadroparin ) or at therapeutic doses only during the first month of treatment followed by a prophylactic phase at half dose ( Parnaparin ) . A r and omized prospect i ve study was carried out on patients under observation with a recent diagnosis of DVT . The objectives of the study were to confirm the effectiveness of therapy with LMWH in terms of prevention of the risk of thromboembolism , of relapse of DVT , and of hemorrhagic complications , and to complete an evaluation of venous recanalization and residual valve competence in the 2 groups of patients . From December 2002 to June 2005 , we r and omized a total of 91 patients ( 51 in the Parnaparin group and 40 in the Nadroparin group ) . Overall , there was 1 case of nonfatal pulmonary embolism ( 1.1 % ) at 7 days into therapy with LMWH . There were 3 cases ( 3.3 % ) of progression of thrombosis despite therapy with LMWH , 2 cases ( 5 % ) in the Nadroparin group , and 1 case ( 2 % ) in the Parnaparin group ( P = NS ) , and after suspension of the therapy , there was 1 case of relapse of thrombosis . Three of the 4 thrombotic events occurred in patients with active neoplasia . Moreover , only 1 major hemorrhagic event ( 1.1 % ) required blood transfusion . The Doppler ultrasound in the follow-up showed a complete resolution of 56 % of the vein thromboses at an average of 6.1 ± 4.6 ( mean ± SD ) months . Valve competence recovered in 65.9 % of cases with no significant difference between the 2 heparin groups . Home treatment of sural and femoral-popliteal DVT using LMWH represents a safe and effective method in the prevention of pulmonary embolism and encourages the process of recanalization of the thrombosed vessel , especially in cases of sural and /or popliteal DVT . Administration can be carried out with the same degree of safety at the therapeutic dose throughout the period of treatment or can be halved after the first month of treatment . In patients with active neoplasia , treatment with oral anticoagulant therapy must be considered PURPOSE The purpose of this study was to compare the efficacy and safety of treating mobile iliofemoral patients with deep venous thrombosis ( DVT ) with subcutaneous low-molecular-weight heparin ( dalteparin sodium ) either 200 IU/kg once-daily ( group 1 ) or 100 IU/kg twice-daily ( group 2 ) . METHODS Consecutive patients with suspected iliofemoral DVT diagnosed by duplex ultrasonography and verified by radionuclide venography were r and omized to one of the two low-molecular-weight heparin ( LMWH ) regimens . Perfusion and when necessary ventilation scans were performed for diagnosis of pulmonary emboli ( PE ) in all patients immediately after admission and were repeated after approximately 10 days , whereupon oral anticoagulation was started unless contraindicated . Minimal and maximal anti-factor Xa activity was measured after 2 to 3 days of therapy . All patients were kept mobile with compression b and ages . The primary end point was reduction in frequency of PE as assessed on the second lung scan . RESULTS A total of 140 patients with confirmed DVT were r and omized , 76 to group 1 and 64 to group 2 . The two groups were comparable in their baseline clinical characteristics . In the initial lung scans 36 ( 47.4 % ) patients in group 1 and 29 ( 45.3 % ) patients in group 2 had objective ly verified PE , but only 11 ( 14.5 % ) and 8 ( 12.5 % ) patients , respectively , had symptoms . After dalteparin treatment PE disappeared in two patients in group 1 , but in two other cases new PEs occurred , ( NS ) . In group 2 a resolution of PEs was observed in eight patients , whereas only one new PE could be detected . This change reflects the efficacy of therapy as defined by resolution of existing PEs and by the occurrence of new PEs and is statistically significant according to McNemar 's chi-square test with the exact binomial method pair procedure ( p < 0.05 ) . Symptomatic PE was reduced from 14.5 % to 5.3 % in group 1 ( 96 % to CI for the difference , -1.5 % to + 17.3 % ) and from 12.5 % to 1.6 % in group 2 ( 95 % CI for the difference 0.7 % to 18 % , p < 0.05 ) . There was one single fatal PE , one serious and three minor bleeding episodes in group 1 , and one minor bleeding episode in group 2 ( 95 % CI for the difference : -3.6 % to + 8.1 % ) . CONCLUSIONS Treatment of ambulant iliofemoral patients with DVT with 100 IU/kg dalteparin twice-daily appears to be moe safe and effective than 200 IU/kg given once-daily . Bed rest is not necessary for treating mobile patients Treatment of deep venous thrombosis with low molecular weight heparin ( LMWH-Novo , Logiparin ) was carried out with two different doses of Logiparin , 75 XaI U/kg b.w . twice daily and 150 XaI U/kg b.w . once daily subcutaneously for 5 days . Simultaneously warfarin was given from the first day of heparin treatment . Mean age of the twenty patients was 65 years and one third was females . No serious side effects , hematomas , pulmonary emboli or signs of recurrent thrombosis occurred during treatment with either dose regime . Venografic assessment with Marder scoring one week after initiation of Logiparin treatment showed a slight not significant improvement apparent in 40 % of the patients . The activities of F-IIaI and F-XaI in the blood plasma were found to increase after injection of Logiparin . These two parameters seem to be the most suitable for monitoring the effect during treatment . For future studies on the therapeutic effect of Logiparin in deep venous thrombosis a single dose of 150 to 200 F-XaI activity per 24 hours seems to be most suitable INTRODUCTION Trials comparing the use of full dose unfractionated heparin ( UFH ) or low molecular weight heparins ( LMWHs ) in very elderly patients with impaired renal function are lacking . IRIS aim ed to assess whether LMWH is at least as safe as UFH in this population . MATERIAL S AND METHODS The study included renally impaired patients ≥70 years with acute symptomatic lower limb deep vein thrombosis ( DVT ) . Patients were r and omized to initial treatment with either tinzaparin 175 IU/kg once daily ( n=269 ) or activated partial thromboplastin time-adjusted UFH twice daily ( n=270 ) . After acute management both groups received vitamin K antagonist to day 90 . RESULTS The trial was stopped prematurely due to a difference in mortality favoring the UFH group ( 11.5 vs. 6.3 % ; p=0.035 ) . Rates of clinical ly relevant bleedings by day 90 were similar in the tinzaparin ( 11.9 % ) and UFH ( 11.9 % ) groups , as were rates of confirmed recurrent venous thromboembolism ( VTE ) ( 2.6 vs. 1.1 % ; p=0.34 ) . As the mortality difference could not be explained by bleedings or recurrent VTE , a post-hoc analysis was performed . This identified six baseline characteristics significantly correlated with mortality , of which five were over-represented in the tinzaparin group . CONCLUSION The IRIS study was a challenging study involving patients ( mean age 83 years ) usually excluded from clinical studies , but its early termination has left questions unanswered . The mortality difference observed with tinzaparin vs. UFH in elderly , renally-impaired patients with DVT can not be explained on the basis of bleedings or recurrent VTE , and may reflect an imbalance of mortality risk factors at baseline BACKGROUND Optimal doses and duration of low-molecular-weight heparin ( LMWH ) for the treatment of superficial vein thrombosis ( SVT ) are still uncertain . OBJECTIVES To compare the efficacy and safety of different doses and duration s of LMWH parnaparin for symptomatic lower limb SVT . PATIENTS AND METHODS Out patients with at least a 4-cm-long SVT of long or short saphenous veins or their collaterals were r and omized to receive parnaparin either 8500 UI once daily ( o.d . ) for 10 days followed by placebo for 20 days ( group A ) or 8500 UI o.d . for 10 days followed by 6400 UI once daily ( o.d . ) for 20 days ( group B ) or 4250 UI o.d . for 30 days ( group C ) in a double-blind fashion in 16 clinics . Primary outcome was the composite of symptomatic and asymptomatic deep vein thrombosis ( DVT ) , symptomatic pulmonary embolism ( PE ) and relapse and /or symptomatic or asymptomatic SVT recurrence in the first 33 days with 60 days follow-up . RESULTS Among 664 patients , primary outcome occurred in 33/212 ( 15.6 % ) , 4/219 ( 1.8 % ) and 16/217 ( 7.3 % ) subjects in groups A , B and C , respectively ( B vs. A : absolute risk reduction [ ARR ] : 13.7 % , 95 % confidence intervals [ CI ] : 8 - 18.9 P<0.001 ; B vs. C : ARR : 5.5 % ; 95 % CI : 1.6 - 9.4 P= 0.011 ; C vs. A : ARR : 8.2 % , 95 % CI : 2 - 14 P=0.012 ) . During days 0 - 93 , the event rate was higher in group A ( 22.6 % ) than either in group B ( 8.7 % ; P=0.001 ) or C ( 14.3 % , P=0.034 ) . No major hemorrhages occurred . CONCLUSIONS An intermediate dose of parnaparin for 30 days is superior to either a 30-day prophylactic dose or a 10-day intermediate dose for lower limb SVT treatment Treatment monitoring based on a laboratory parameter increases the efficacy and safety of st and ard heparin therapy , but it is not known if this also applies to low-molecular-weight heparin ( LMWH ) therapy of acute deep vein thrombosis ( DVT ) . In a prospect i ve r and omized trial involving 122 consecutive patients , group A ( 58 patients ) received a weight adjusted dose of Fragmin ( 100 IU/kg ) subcutaneously twice a day throughout the treatment period ( 10 days + /- 1 ) , while in group B ( 64 patients ) the dosage was based on the results of an anti factor Xa ( anti Xa ) amidol \n Output:\n " }, { "from": "agent", "value": "AUTHORS ' CONCLUSIONS Once daily treatment with LMWH is as effective and safe as twice daily treatment with LMWH" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: AIMS To evaluate the long-term durability of the efficacy of alogliptin compared with glipizide in combination with metformin in people with type 2 diabetes inadequately controlled on stable-dose metformin . METHODS This multicentre , double-blind , active-controlled study r and omized 2639 patients aged 18 - 80 years to 104 weeks of treatment with metformin in addition to alogliptin 12.5 mg once daily ( n = 880 ) , alogliptin 25 mg once daily ( n = 885 ) or glipizide 5 mg once daily , titrated to a maximum of 20 mg ( n = 874 ) . The primary endpoint was least square mean change from baseline in HbA1c level at 104 weeks . RESULTS The mean patient age was 55.4 years , the mean diabetes duration was 5.5 years and the mean baseline HbA1c was 7.6 % . HbA1c reductions at week 104 were -0.68 % , -0.72 % and -0.59 % for alogliptin 12.5 and 25 mg and glipizide , respectively [ both doses met the criteria for non-inferiority to glipizide ( p<0.001 ) ; alogliptin 25 mg met superiority criteria ( p=0.010 ) ] . Fasting plasma glucose concentration decreased by 0.05 and 0.18 mmol/l for alogliptin 12.5 and 25 mg , respectively , and increased by 0.30 mmol/l for glipizide ( p < 0.001 for both comparisons with glipizide ) . Mean weight changes were -0.68 , -0.89 and 0.95 kg for alogliptin 12.5 and 25 mg and glipizide , respectively ( p < 0.001 for both comparisons with glipizide ) . Hypoglycaemia occurred in 23.2 % of patients in the glipizide group vs. 2.5 and 1.4 % of patients in the alogliptin 12.5 and 25 mg groups , respectively . Pancreatitis occurred in one patient in the alogliptin 25 mg group and three in the glipizide group . CONCLUSIONS Alogliptin efficacy was sustained over 2 years in patients with inadequate glycaemic control on metformin alone Background The aim of his study was to compare the efficacy of pioglitazone with metformin on the reduction of albuminuria in type 2 diabetic patients with hypertension and microalbuminuria treated with renin – angiotensin system inhibitors ( RAS-Is ) . Methods The open-label , r and omized trial was performed in type 2 diabetic patients with hypertension and microalbuminuria . On the basis of the treatment with RAS-Is , 68 patients with microalbuminuria received either pioglitazone ( 15–30 mg/day ; n = 32 ) or metformin ( 500–750 mg/day ; n = 31 ) for 52 weeks . Urinary albumin-to-creatinine ratio ( UACR ) was measured every 12 weeks . Results After 52 weeks of treatment , the changes in the log-UACR from baseline were −8.3 % in the pioglitazone group and + 4.2 % in the metformin group ( p = 0.01 ) , with similar glycemic and blood pressure changes . Conclusion The combination of pioglitazone and RAS-Is showed therapeutic benefit in the reduction of urinary albumin excretion for type 2 diabetic patients with hypertension and microalbuminuria OBJECTIVE Although initially effective , sulfonylureas are associated with poor glycemic durability , weight gain , and hypoglycemia . Dapagliflozin , a selective inhibitor of sodium-glucose cotransporter 2 ( SGLT2 ) , reduces hyperglycemia by increasing urinary glucose excretion independent of insulin and may cause fewer of these adverse effects . We compared the efficacy , safety , and tolerability of dapagliflozin with the sulfonylurea glipizide in patients with type 2 diabetes inadequately controlled with metformin monotherapy . RESEARCH DESIGN AND METHODS This 52-week , double-blind , multicenter , active-controlled , noninferiority trial r and omized patients with type 2 diabetes ( baseline mean HbA1c , 7.7 % ) , who were receiving metformin monotherapy , to add-on dapagliflozin ( n = 406 ) or glipizide ( n = 408 ) up-titrated over 18 weeks , based on glycemic response and tolerability , to ≤10 or ≤20 mg/day , respectively . RESULTS The primary end point , adjusted mean HbA1c reduction with dapagliflozin ( −0.52 % ) compared with glipizide ( −0.52 % ) , was statistically noninferior at 52 weeks . Key secondary end points : dapagliflozin produced significant adjusted mean weight loss ( −3.2 kg ) versus weight gain ( 1.2 kg ; P < 0.0001 ) with glipizide , significantly increased the proportion of patients achieving ≥5 % body weight reduction ( 33.3 % ) versus glipizide ( 2.5 % ; P < 0.0001 ) , and significantly decreased the proportion experiencing hypoglycemia ( 3.5 % ) versus glipizide ( 40.8 % ; P < 0.0001 ) . Events suggestive of genital infections and lower urinary tract infections were reported more frequently with dapagliflozin compared with glipizide but responded to st and ard treatment and rarely led to study discontinuation . CONCLUSIONS Despite similar 52-week glycemic efficacy , dapagliflozin reduced weight and produced less hypoglycemia than glipizide in type 2 diabetes inadequately controlled with metformin . Long-term studies are required to further evaluate genital and urinary tract infections with SGLT2 inhibitors OBJECTIVE To evaluate the effect on coagulation and fibrinolysis parameters and on non-conventional cardiovascular risk factors of metformin plus nateglinide or glibenclamide in naïve type 2 diabetes patients . PATIENTS AND METHODS A total of 248 type 2 diabetic patients were enrolled and r and omly assigned to receive nateglinide or glibenclamide , and metformin for 12 months . We assessed body mass index ( BMI ) , glycated hemoglobin ( HbA1c ) , fasting plasma glucose ( FPG ) , postpr and ial plasma glucose ( PPG ) , fasting plasma insulin ( FPI ) , postpr and ial plasma insulin ( PPI ) , homeostasis model assessment index ( HOMA index ) , lipid profile with lipoprotein ( a ) [ Lp(a ) ] , fibrinogen ( Fg ) , plasminogen activator inhibitor-1 ( PAI-1 ) , tissue plasminogen activator ( t-PA ) , homocysteine ( Hcy ) , systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) . RESULTS After 9 months of treatment , both tested drug combinations were similarly associated with a significant reduction in FPG ( nateglinide , -17.2 % ; glibenclamide , -16.9 % , both p<0.05 ) compared to the baseline , while HbA1c ( -17.3 % , p<0.05 ) and PPG ( -15.2 % , p<0.05 ) significantly decreased only in the nateglinide group . After one year of treatment , compared to the baseline the nateglinide group showed a significant reduction in HbA1c ( -21 % , p<0.01 ) , FPG ( -20.7 % ) , p<0.01 , PPG ( -21.5 % , p<0.05 ) , HOMA index ( -25.4 % , p<0.05 ) ; the glibenclamide group , showed a significant reduction in HbA1c ( -11 % , p<0.05 ) , FPG ( -23.2 % , p<0.05 ) , PPG ( -11.2 % , p<0.05 ) , and HOMA index ( -23.9 % , p<0.05 ) but to a minor extent . Moreover , the HbA1c difference value from baseline observed in the nateglinide-treated group was significantly higher than that observed in the glibenclamide group . Therefore the nateglinide-treated patients showed a significant reduction in some prothrombotic parameters ( PAI-1=-19 % , Lp(a)=-31 % , and Hcy=-32.3 % , all p<0.05 ) , whereas the glibenclamide-treated patients did not . CONCLUSION Nateglinide appears to improve glycemic control as well as the levels of some prothrombotic parameters compared to glibenclamide when administered in combination with metformin Background Hypertension and type 2 diabetes are common co-morbidities . Preliminary studies suggest that thiazolidinediones reduce blood pressure ( BP ) . We therefore used ambulatory BP to quantify BP lowering at 6–12 months with rosiglitazone used in combination with metformin or sulfonylureas compared to metformin and sulfonylureas in people with type 2 diabetes . Methods Participants ( n = 759 ) in the multicentre RECORD study were studied . Those taking metformin were r and omized ( open label ) to add-on rosiglitazone or sulfonylureas , and those on sulfonylurea to add-on rosiglitazone or metformin . Results 24-Hour ambulatory BP was measured at baseline , 6 months and 12 months . At 6 and 12 months , reductions in 24-hour ambulatory systolic BP ( sBP ) were greater with rosiglitazone versus metformin ( difference at 6 months 2.7 [ 95 % CI 0.5–4.9 ] mmHg , p = 0.015 ; 12 months 2.5 [ 95 % CI 0.2–4.8 ] mmHg , p = 0.031 ) . Corresponding changes for ambulatory diastolic BP ( dBP ) were comparable ( 6 months 2.7 [ 95 % CI 1.4–4.0 ] mmHg , p < 0.001 ; 12 months 3.1 [ 95 % CI 1.8–4.5 ] mmHg , p < 0.001 ) . Similar differences were observed for rosiglitazone versus sulfonylureas at 12 months ( sBP 2.7 [ 95 % CI 0.5–4.9 ] mmHg , p = 0.016 ; dBP 2.1 [ 95 % CI 0.7–3.4 ] mmHg , p = 0.003 ) , but differences were smaller and /or not statistically significant at 6 months ( sBP 1.5 [ 95 % CI -0.6 to 3.6 ] mmHg , p = NS ; dBP 1.3 [ 95 % CI 0.0–2.5 ] mmHg , p = 0.049 ) . Changes in BP were not accompanied by compensatory increases in heart rate , did not correlate with basal insulin sensitivity estimates and were not explained by changes in antihypertensive therapy between the various strata . Conclusion When added to metformin or a sulfonylurea , 12-month treatment with rosiglitazone reduces ambulatory BP to a greater extent than when metformin and a sulfonylurea are combined . Trial registration NCT00379769 http:// clinical Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the \n Output:\n " }, { "from": "agent", "value": "Results for M+S versus metformin monotherapy were inconclusive .\nAUTHORS ' CONCLUSIONS There is inconclusive evidence whether M+S combination therapy compared with metformin plus another glucose-lowering intervention results in benefit or harm for most patient-important outcomes ( mortality , SAEs , macrovascular and microvascular complications ) with the exception of hypoglycaemia ( more harm for M+S combination ) .\nNo RCT reported on health-related quality of life" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: BACKGROUND Adjuvant chemotherapy is associated with poor quality of life ( qol ) in breast cancer patients . We tested the effect of listening to music during chemotherapy on quality of life in these patients . MATERIAL / METHODS We tested in a prospect i ve cohort the changes in qol scores as assessed by European Organization for Research and Treatment of Cancer Quality of Life Question naire ( EORTC QLQ-C30 ) , and the influence of listening to non-preferred music at the chemotherapy unit on these parameters in a mixed linear model by repeated measures analysis of variance ( RMANOVA ) . RESULTS For the whole cohort , musical intervention was not associated with a change in any dimension of quality of life . However ; the music effect significantly interacted with patient age ; patients > 45 years old had improved insomnia and appetite loss scores after musical intervention ( F = 6.76 , P = 0.019 and F = 11.22 , P = 0.004 , respectively ) . CONCLUSIONS Our results show that brief , non-preferred music exposure at the time of chemotherapy administration does not improve quality of life in patients with early breast cancer . Nonetheless , there is still a possibility that a subgroup will benefit from this approach as suggested by the interaction of the music effect with patient age The treatment of pain continues to gain in saliency as a component of defining best practice in medical care . Music therapy is an integrative treatment modality that impacts patient outcomes in the treatment of spinal pain . At Mount Sinai Beth Israel , we conducted a mixed- methods study addressing the effects of music therapy interventions on the recovery of patients after spine surgery . The study combined st and ard medical approaches and integrative music therapy . Sixty patients ( 35 female , 25 male ) ranging in age from 40 to 55 years underwent anterior , posterior , or anterior-posterior spinal fusion and were r and omly assigned to either music therapy plus st and ard care ( medical and nursing care with scheduled pharmacologic pain intervention ) or st and ard care only . Measurements for both groups were completed before and after the intervention . Music therapy involved the use of patient-preferred live music that supported tension release/relaxation through incentive-based clinical improvisation , singing , and /or rhythmic drumming or through active visualization supported by live music that encompasses tension resolution . The control and music groups showed significant differences in degree and direction of change in the visual analog scale ( VAS ) pain ratings from before to after intervention ( P = .01 ) . VAS pain levels increased slightly in the control group ( to 5.87 from 5.20 ) but decreased by more than 1 point in the music group ( to 5.09 from 6.20 ) . The control and music therapy groups did not differ in the rate of change in scores on Hospital Anxiety and Depression Scale ( HADS ) Anxiety ( P = .62 ) , HADS Depression ( P = .85 ) , or Tampa Scale for Kinesiophobia ( P = .93 ) . Both groups had slight increases in HADS Anxiety , comparable decreases in HADS Depression , and minimal changes in fear-related movement ( Tampa scale ) Goals of workPrevention of chemotherapy-induced nausea and vomiting ( CINV ) with st and ard antiemetics has been more difficult to achieve in female patients . Data from two phase III trials of the NK1 antagonist aprepitant were assessed for potential effect of gender on treatment response . Patients and methods 1,044 patients receiving cisplatin ( ≥70 mg/m2 ) were r and omly assigned to control regimen [ ondansetron ( O ) 32 mg i.v . and dexamethasone ( D ) 20 mg p.o . on day 1 ; D 8 mg twice daily on days 2–4 ] or aprepitant ( A ) regimen ( A 125 mg p.o . plus O 32 mg and D 12 mg on day 1 ; A 80 mg and D 8 mg once daily on days 2–3 ; and D 8 mg on day 4 ) . The primary endpoint was overall complete response ( no emesis and no rescue therapy over days 1–5 ) . Data were analyzed by a modified intent-to-treat approach . Between-treatment comparisons for each gender were made using logistic regression . Main results Women comprised 42 and 43 % of the aprepitant and control groups , respectively . In the control group , 41 % of women had overall complete response compared with 53 % of men . In the aprepitant group , 66 % of women had overall complete response compared with 69 % of men . Conclusion The addition of aprepitant may negate the adverse prognostic effect of female gender on the prevention of CINV in patients receiving highly emetogenic chemotherapy PURPOSE To examine the effect of patient-selected music intervention during daily weaning trials for patients on prolonged mechanical ventilation . METHODS Using a crossover repeated measures design , patients were r and omized to music vs no music on the first intervention day . Provision of music was alternated for 6 days , result ing in 3 music and 3 no music days . During weaning trials on music days , data were obtained for 30min prior to music listening and continued for 60min while patients listened to selected music ( total 90min ) . On no music days , data were collected for 90min . Outcome measures were heart rate ( HR ) , respiratory rate ( RR ) , oxygen saturation ( SpO2 ) , blood pressure ( BP ) , dyspnea and anxiety assessed with a visual analog scale ( VAS-D , VAS-A ) and weaning duration ( meanh per day on music and non-music days ) . RESULTS Of 31 patients r and omized , 23 completed the 6-day intervention . When comparisons were made between the 3 music and 3 no music days , there were significant decreases in RR and VAS-D and a significant increase in daily weaning duration on music days ( p<0.05 ) . A multivariate mixed-effects model analysis that included patients who completed ≥2 days of the intervention ( n=28 ) demonstrated significant decreases in HR , RR , VAS-A , and VAS-D and a significant increase in daily weaning duration on music days ( p<0.05 ) . CONCLUSIONS Providing patient selected music during daily weaning trials is a simple , low-cost , potentially beneficial intervention for patients on prolonged mechanical ventilation . Further study is indicated to test ability of this intervention to promote weaning success and benefits earlier in the weaning process PURPOSE / OBJECTIVES To test whether use of music as a diversional intervention during high-dose chemotherapy administration would affect perception of nausea and episodes of vomiting . SAMPLE 39 patients undergoing bone marrow transplant . A total of 33 patients were included in the data analysis , with 17 in the control group and 16 in the music intervention group . METHODS Patients were assigned r and omly to a control group ( usual antiemetic protocol ) or the experimental group ( usual antiemetic group plus music intervention during the 48 hours of high-dose cyclophosphamide administered as part of the preparative regimen ) . MAIN RESEARCH VARIABLES Use of a music intervention , perception of nausea , and instances of vomiting . FINDINGS Significant differences were found between group scores on a visual analog scale for nausea and number of episodes of vomiting , demonstrating that the experimental group experienced less nausea and fewer instances of vomiting . CONCLUSION This study found that music is an effective adjunct to a pharmacologic antiemetic regimen for lessening nausea and vomiting , and this study merits further investigation through a larger multi-institutional effort . IMPLICATION S FOR NURSING PRACTICE Using music as a diversional adjunct intervention to antiemetic therapy is helpful in decreasing nausea and vomiting . The intervention can be initiated independently by nurses and individualized for each patient , leading to greater patient comfort and compliance with high-dose chemotherapy Purpose Despite significant advances in antiemetic management , almost 50 % of cancer patients still experience nausea and vomiting during treatment . The goal of antiemetic therapy is complete prevention of treatment-induced nausea and /or vomiting ( TINV ) ; however , realisation of this goal remains elusive , thus supplementary strategies identifying patients at high risk must be employed in the interim . Consequently , we examined TINV incidence and its risk factors , including patient , clinical and pretreatment quality of life (QOL)/psychological factors . Methods Two hundred newly diagnosed cancer patients beginning combined treatment participated in this prospect i ve , longitudinal , observational study . QOL ( including TINV ) , psychological adjustment , and patient/ clinical characteristics were examined at pretreatment , on-treatment ( 8 weeks ± 1 week ) and post-treatment . Results Overall , 62 % of patients experienced TINV , with TIN incidence ( 60 % ) doubling that of TIV ( 27 % ) . Eight independent risk factors predicted 73 % of TIN incidence : high premorbid/anticipatory NV , moderately/highly emetogenic chemotherapy ( M/HEC ) , longer treatment ( > 3 months ) , female gender , surgery prior to adjuvant chemotherapy ± radiotherapy , private health insurance and low emotional functioning ( pretreatment ) . Six independent risk factors predicted 77 % of TIV incidence : premorbid/anticipatory vomiting , M/HEC , female gender , cancer resection and low role functioning ( pretreatment ) . Conclusions TINV still represents a very major concern for patients . Several pretreatment risk factors for the development of TIN and TIV , respectively , were identified . Patients about to undergo cancer treatment , particularly combined treatment involving emetogenic chemotherapy and surgery , should be screened for these factors with a view to modifying st and ard pretreatment/maintenance antiemetic therapy . Furthermore , and consistent with recent research , it is recommended that more comprehensive interventions combining antiemetics with other effective pharmacological ( e.g. anxiolytics ) and non-pharmacological approaches ( e.g. acupuncture , relaxation techniques ) be considered by clinicians in attempts to improve control of TIN and TIV ( and overall QOL ) for their patients . In this way , optimal holistic care will be ensured for cancer patients by clinicians providing conventional oncology treatment PURPOSE Pharmacological therapy is only partially effective in preventing or treating chemotherapy induced nausea and vomiting ( CINV ) . Therefore , exploring the complementary role of non-pharmacological approaches used in addition to pharmacological agents is important . Nevasic uses specially constructed audio signals hypothesized to generate an antiemetic reaction . The aim of this study was to examine the feasibility of conducting a r and omized controlled trial ( RCT ) to evaluate the effectiveness of Nevasic to control CINV . METHODS A mixed methods design incorporating an RCT and focus group interviews . For the RCT , female breast cancer patients were r and omized to receive either Nevasic plus usual care , music plus usual care , or usual care only . Data were analysed using descriptive statistics and linear mixed-effects models . Five focus group interviews were conducted to obtain participants ' views regarding the acceptability of the interventions in the trial . RESULTS 99 participants were recruited to the RCT and 15 participated in focus group interviews . Recruitment targets were achieved . Issues of Nevasic acceptability were highlighted as weaknesses of the program . This study did not detect any evidence for the effectiveness of Nevasic ; however , the results showed statistically significant less use of anti-emetics ( p = 0.003 ) and borderline non-significant improvement in quality of life ( p = 0.06 ) . CONCLUSIONS Conducting a non-pharmacological intervention using such an audio program is feasible , although difficulties and limitations exist with its use . Further studies are required to investigate the effectiveness of Nevasic from perspectives such as anti-emetic use , as well as its overall effect on the levels of nausea and vomiting Goals of workA number of prognostic factors have been identified as risk factors for chemotherapy-induced emesis . This post-hoc analysis addressed whether : ( 1 ) these prognostic factors can identify a low-risk group for whom ondansetron plus dexamethasone alone provide a high level of protection ( ≥80 % no emesis ) ; ( 2 ) the NK1 receptor antagonist aprepitant improves antiemetic outcome regardless of emetic risk . Patients and methods Breast cancer patients in a phase III double-blind , placebo-controlled trial were r and omized to antiemetic regimens including ondansetron and dexamethasone , or aprepitant , ondansetron , and dexamethasone . Multivariate logistic regression models were used to assess the impact on emesis ( but not nausea ) of the regimen with aprepitant , and previously reported risk factors , including age ( < 55 and ≥55 years ) , ethanol use ( 0–4 or ≥5 drinks/week ) , history of pregnancy-related morning sickness , and history of motion sickness , using a modified intent-to-treat approach . Results Treatment with aprepitant ( P < 0.0001 ) , older age ( P = 0.006 ) , ethanol use ( P = 0.0048 ) , and no history of morning sickness ( P = 0.0007 ) were all significantly associated with reduced likelihood of emesis . The proportion of patients with one , two , or three risk factors who remained emesis free was significantly higher with the aprepitant-containing regimen than with the active control ( 70.2–82.8 % vs. 38.6–66.4 % , respectively ) . Conclusions Aprepitant markedly improved control of emesis in patients with one or more risk factors . This analysis did not support using risk factors for modifying the antiemetic approach . A low-risk group with zero risk factors for whom aprepitant provided little benefit was \n Output:\n " }, { "from": "agent", "value": "Locus of control for music selection was more often with the investigator rather than the participant .\nIMPLICATION S FOR RESEARCH The existing data have been largely generated by nurse scientists , and implication s for nursing practice are many , because music interventions are low-cost , easily accessible , and without known adverse effects ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Objectives Primary : To compare the effectiveness of intensive group and individual interventions for smoking cessation in a primary health care setting ; secondary : to identify the variables associated with smoking cessation . Methods Three-pronged clinical trial with r and omisation at the individual level . We performed the following : an intensive individual intervention ( III ) , an intensive group intervention ( IGI ) and a minimal intervention ( MI ) . Included in the study were smokers who were prepared to quit smoking . Excluded from the study were individuals aged less than 18 years or with severe mental conditions or terminal illnesses . The outcome measure was continued abstinence at 12 months confirmed through CO-oximetry ( CO ) . The analysis was based on intention to treat . Results In total , 287 smokers were recruited : 81 in the III , 111 in the IGI , and 95 in the MI . Continued abstinence at 12 months confirmed through CO was 7.4 % in the III , 5.4 % in the IGI , and 1 % in the MI . No significant differences were noted between III and MI on the one h and , and between IGI and MI on the other [ RR 7.04 ( 0.9 - 7.2 ) and RR 5.1 ( 0.6 - 41.9 ) , respectively ] . No differences were noted between IGI and III [ RR 0.7 ( 0.2 - 2.2 ) ] . In multivariate analysis , only overall visit length showed a statistically significant association with smoking cessation . Conclusions The effectiveness of intensive smoking interventions in this study was lower than expected . No statistically significant differences were found between the results of individual and group interventions .Trial registration numberIS RCT Smoking cessation treatment is now integrated into many health-care systems and a major research effort is under way to improve current success rates . Until now results from r and omized clinical trials have been reported in many different ways , leading to problems of interpretation . We propose six st and ard criteria comprising the ' Russell St and ard ' ( RS ) . These criteria are applicable to trials of cessation aids where participants have a defined target quit date and there is face-to-face contact with research ers or clinic staff , as follows . ( 1 ) Follow-up for 6 months ( RS6 ) or 12 months ( RS12 ) from the target quit date or the end of a predefined ' grace period ' ; ( 2 ) self-report of smoking abstinence over the whole follow-up period allowing up to five cigarettes in total ; ( 3 ) biochemical verification of abstinence at least at the 6-month or 12-month follow-up point ; ( 4 ) use of an ' intention-to-treat ' approach in which data from all r and omized smokers are included in the analysis unless they have died or moved to an untraceable address ( participants who are included in the analysis are counted as smokers if their smoking status at the final follow-up can not be determined ) ; ( 5 ) following-up ' protocol violators ' and using their true smoking status in the analysis ; and ( 6 ) collecting follow-up data blind to smokers ' allocation to trial group . We believe that these criteria provide the best compromise between practicability and surrogacy for long-term cessation and will enable meaningful comparison between studies . There may be good reasons why other outcome criteria would also be reported , and studies that involve interventions with special groups or where there is no design ated target quit date or face to face contact would need to adapt these criteria accordingly OBJECTIVE To evaluate the smoking cessation efficacy of nicotine patch therapy as an adjunct to low-intensity , primary care intervention . DESIGN R and omized , placebo-controlled , double-blind , multisite trial . SETTING S Twenty-one primary care sites in Nebraska . PATIENTS A total of 369 smokers of 20 or more cigarettes per day . INTERVENTION Two brief primary care visits for smoking intervention with 10 weeks of active or placebo-patch therapy . MAIN OUTCOME MEASURES Confirmed self-reported abstinence 3 , 6 , and 12 months after the quit day . RESULTS Compared with placebo control subjects , participants assigned nicotine patches had higher 3-month ( 23.4 % vs 11.4 % ; P < .01 ) and 6-month ( 18.5 % vs 10.3 % ; P < .05 ) abstinence rates . The 1-year abstinence rates for the active and placebo patch groups were 14.7 % and 8.7 % , respectively ( P = .07 ) . Of smokers aged 45 years and older , 9 ( 18.8 % ) of 48 using active patches compared with 0 of 31 using placebo patches achieved 12-month abstinence ( chi 2 = 6.56 ; P < .05 ) . Among those with high nicotine dependency scores ( Fagerstrom score > or = 7 ) , 1-year abstinence rates were significantly higher in the nicotine patch group ( 19.1 % ) compared with the placebo group ( 5.0 % ) ( chi 2 = 10.7 ; P = .001 ) . However , there was no significant difference in 1-year quit rates for participants with low Fagerstrom scores ( < 7 ) . CONCLUSIONS Nicotine patch therapy enhanced 6 month quit rates as an adjunct to brief primary care intervention . The highest quit rates were achieved by participants who specifically contacted the site to enroll in the study or to obtain a prescription for nicotine patches . Differences in participant selection factors may account , in part , for the lower smoking cessation rates associated with primary care intervention . Duration of counseling , patient age , and Fagerstrom scores may be important factors related to the long-term smoking cessation success of nicotine patch therapy Background Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease ( COPD ) . But a fewer smoking cessation measures were conducted in communities for smokers with COPD in China . The aim of our study was to assess the preventive effects of behavioral interventions for smoking cessation and potential impact factors in smokers with COPD in China . Methods In a r and omised controlled smoking cessation trial 3562 patients with COPD who were current smoker were allocated to intervention group received behavioral intervention and control group received the usual care for two years . The primary efficacy endpoint was the complete and continuous abstinence from smoking from the beginning of month 24 to the end of month 30 . Participants were followed up at month 48 . Results Continuous smoking abstinence rates from month 24 to 30 were significantly higher in participants receiving behavioral intervention than in those receiving usual care ( 46.4 % vs 3.4 % , p < 0.001 ) . Continuous abstinence rates from months 24 to 36 ( 45.8 % vs 4.0 % ) and months 24 to 48 ( 44.3 % vs 5.1 % ) were also higher in participants receiving behavioral intervention than in those control group . Family members or family physicians/nurses smoking were first identified to influence smoking cessation . Conclusions Behavioral intervention doubled the smoking cessation rate in patients with COPD and was complied well by the general practitioners . The family members and family physicians/nurses smoking were the main risk factors for smoking cessation . Trial registration Chinese Clinical Trials Registration ( ChiCTR-TRC-12001958 ) 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 Background The prevalence of smoking in Spain is high in both men and women . The aim of our study was to evaluate the role of gender in the effectiveness of a specific smoking cessation intervention conducted in Spain . Methods This study was a secondary analysis of a cluster r and omized clinical trial in which the r and omization unit was the Basic Care Unit ( family physician and nurse who care for the same group of patients ) . The intervention consisted of a six-month period of implementing the recommendations of a Clinical Practice Guideline . A total of 2,937 current smokers at 82 Primary Care Centers in 13 different regions of Spain were included ( 2003 - 2005 ) . The success rate was measured by a six-month continued abstinence rate at the one-year follow-up . A logistic mixed-effects regression model , taking Basic Care Units as r and om-effect parameter , was performed in order to analyze gender as a predictor of smoking cessation . Results At the one-year follow-up , the six-month continuous abstinence quit rate was 9.4 % in men and 8.5 % in women ( p = 0.400 ) . The logistic mixed-effects regression model showed that women did not have a higher odds of being an ex-smoker than men after the analysis was adjusted for confounders ( OR adjusted = 0.9 , 95 % CI = 0.7 - 1.2 ) . Conclusions Gender does not appear to be a predictor of smoking cessation at the one-year follow-up in individuals presenting at Primary Care Centers . Clinical Trials.gov IdentifierNCT00125905 OBJECTIVES To determine the long-term effect of a community-based risk reduction intervention at five years after completion of a one-year r and omized clinical trial and to determine the sustainability of the beneficial effects seen one year after the intervention . METHODS 30- to 59- year-old African American siblings of prob and s with premature coronary heart disease ( CHD ) were r and omized for care of multiple CHD risk factors to either one year of community-based care ( CBC ) provided by a nurse practitioner/community health worker team or enhanced usual care ( EUC ) . At five years , 307 ( 84.6 % ) of the siblings returned for reevaluation . MAIN OUTCOME MEASURES Changes in and achievement of goal levels of low-density lipoprotein cholesterol ( LDL-C ) , systolic and diastolic blood pressure ( SBP and DBP , respectively ) , and smoking cessation at five years . RESULTS No significant differences were seen between groups in mean LDL-C , SBP , and DBP or in the overall percentages achieving goal LDL-C , blood pressure , or smoking status . Changes after completion of the intervention suggest that the CBC group lost the beneficial effects for mean LDL-C and for percentage at goal LDL-C , while the EUC group continued to improve . CBC was associated with greater sustainability and less refractoriness of one-year results for LDL-C and blood pressure goals . CONCLUSIONS Although no group differences were found in mean risk factor levels at five years , data indicate that CBC is both feasible and associated with earlier sustainability of positive risk factor changes compared with EUC BACKGROUND Smoking-related morbidity and mortality , and benefits associated with quitting , extend across the life span . Health care provider interventions enhance quitting . The present study examined perceived influence of physician advice to quit and characteristics of subjects receiving this advice . METHODS Subjects were 1,454 smokers ages 50 + with at least one physician visit in the past year . Subjects were surveyed at baseline for receipt of and reactions to physician advice to quit and for smoking , health , and demographic characteristics . RESULTS Over half of subjects welcomed physician advice to quit , about half said the advice influenced their quitting decision \" extremely \" or \" quite a lot , \" and about one-third indicated that it increased their confidence in quitting . Physicians were more likely to advise sicker patients , indicated by poorer health status , at least one past year hospitalization , and presence of cardiovascular , cerebrovascular , or respiratory diseases . CONCLUSIONS Midlife and older smokers \n Output:\n " }, { "from": "agent", "value": "Behavioural interventions were effective and had a dose – response effect .\nBoth nicotine replacement and bupropion therapy were safe and effective , with no observed differences .\nConclusions Multicomponent/complex interventions in PC are effective and safe , appearing to achieve greater long-term continuous smoking cessation than usual care and counselling alone .\nOur results show that smoking interventions should include more than one component and a strong follow-up of the patient to maximise results" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n 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 A novel Hebbian stimulation paradigm was employed to examine physiological correlates of motor memory formation in humans . Repetitive pairing of median nerve stimulation with transcranial magnetic stimulation over the contralateral motor cortex ( paired associative stimulation , PAS ) may decrease human motor cortical excitability at interstimulus intervals of 10 ms ( PAS10 ) or increase excitability at 25 ms ( PAS25 ) . The properties of this plasticity have previously been shown to resemble associative timing-dependent long-term depression ( LTD ) and long-term potentiation ( LTP ) as established in vitro . Immediately after training a novel dynamic motor task , the capacity of the motor cortex to undergo plasticity in response to PAS25 was abolished . PAS10-induced plasticity remained unchanged . When retested after 6 h , PAS25-induced plasticity recovered to baseline levels . After training , normal PAS25-induced plasticity was observed in the contralateral training-naive motor cortex . Motor training did not reduce the efficacy of PAS25 to enhance cortical excitability when PAS10 was interspersed between the training and application of the PAS25 protocol . This indicated that the mechanism supporting PAS25-induced plasticity had remained intact immediately after training . Behavioral evidence was obtained for continued optimization of force generation at a time when PAS25-induced plasticity was blocked in the training motor cortex . Application of the PAS protocol s after motor training did not prevent the consolidation of motor skills evident as performance gains at later retesting . The results are consistent with a concept of temporary suppression of associative cortical plasticity by neuronal mechanisms involved in motor training . Although it remains an open question exactly which element of motor training was responsible for this effect , our findings may link dynamic properties of LTP formation , as established in animal experiments , with human motor memory formation and possibly dynamic motor learning Transcranial direct current stimulation ( tDCS ) is a relatively new non-invasive brain stimulation technique that modulates neural processes . When applied to the human primary motor cortex ( M1 ) , tDCS has beneficial effects on motor skill learning and consolidation in healthy controls and in patients . However , it remains unclear whether tDCS improves motor learning in a general manner or whether these effects depend on which motor task is acquired . Here we compare whether the effect of tDCS differs when the same individual acquires ( 1 ) a Sequential Finger Tapping Task ( SEQTAP ) and ( 2 ) a Visual Isometric Pinch Force Task ( FORCE ) . Both tasks have been shown to be sensitive to tDCS applied over M1 , however , the underlying processes mediating learning and memory formation might benefit differently from anodal transcranial direct current stimulation ( anodal-tDCS ) . Thirty healthy subjects were r and omly assigned to an anodal-tDCS group or sham-group . Using a double-blind , sham-controlled cross-over design , tDCS was applied over M1 while subjects acquired each of the motor tasks over three consecutive days , with the order being r and omized across subjects . We found that anodal-tDCS affected each task differently : the SEQTAP task benefited from anodal-tDCS during learning , whereas the FORCE task showed improvements only at retention . These findings suggest that anodal-tDCS applied over M1 appears to have a task-dependent effect on learning and memory formation Behavioural studies indicate that a newly acquired motor skill is rapidly consoli date d from an initially unstable state to a more stable state , whereas neuroimaging studies demonstrate that the brain engages new regions for performance of the task as a result of this consolidation . However , it is not known where a new skill is retained and processed before it is firmly consoli date d. Some early aspects of motor skill acquisition involve the primary motor cortex ( M1 ) , but the nature of that involvement is unclear . We tested the possibility that the human M1 is essential to early motor consolidation . We monitored changes in elementary motor behaviour while subjects practised fast finger movements that rapidly improved in movement acceleration and muscle force generation . Here we show that low-frequency , repetitive transcranial magnetic stimulation of M1 but not other brain areas specifically disrupted the retention of the behavioural improvement , but did not affect basal motor behaviour , task performance , motor learning by subsequent practice , or recall of the newly acquired motor skill . These findings indicate that the human M1 is specifically engaged during the early stage of motor consolidation Decline in cognitive functions , including impaired acquisition of novel skills , is a feature of older age that impacts activities of daily living , independence , and integration in modern societies Weak transcranial direct current stimulation ( tDCS ) induces persisting excitability changes in the human motor cortex . These plastic excitability changes are selectively controlled by the polarity , duration and current strength of stimulation . To reveal the underlying mechanisms of direct current (DC)-induced neuroplasticity , we combined tDCS of the motor cortex with the application of Na(+)-channel-blocking carbamazepine ( CBZ ) and the N-methyl-D-aspartate (NMDA)-receptor antagonist dextromethorphan ( DMO ) . Monitored by transcranial magnetic stimulation ( TMS ) , motor cortical excitability changes of up to 40 % were achieved in the drug-free condition . Increase of cortical excitability could be selected by anodal stimulation , and decrease by cathodal stimulation . Both types of excitability change lasted several minutes after cessation of current stimulation . DMO suppressed the post-stimulation effects of both anodal and cathodal DC stimulation , strongly suggesting the involvement of NMDA receptors in both types of DC-induced neuroplasticity . In contrast , CBZ selectively eliminated anodal effects . Since CBZ stabilizes the membrane potential voltage-dependently , the results reveal that after-effects of anodal tDCS require a depolarization of membrane potentials . Similar to the induction of established types of short- or long-term neuroplasticity , a combination of glutamatergic and membrane mechanisms is necessary to induce the after-effects of tDCS . On the basis of these results , we suggest that polarity-driven alterations of resting membrane potentials represent the crucial mechanisms of the DC-induced after-effects , leading to both an alteration of spontaneous discharge rates and to a change in NMDA-receptor activation The primary motor cortex ( M1 ) area recruitment enlarges while learning a finger tapping sequence . Also M1 excitability increases during procedural consolidation . Our aim was to investigate whether increasing M1 excitability by anodal transcranial DC stimulation ( AtDCS ) when procedural consolidation occurs was able to induce an early consolidation improvement . Forty-seven right-h and ed healthy participants were trained in a nine-element serial finger tapping task ( SFTT ) executed with the left h and . R and om series blocks were interspersed with training series blocks . Anodal or sham tDCS was administered over the right M1 after the end of the training session . After stimulation , the motor skills of both trained and a new untrained sequential series blocks were tested again . For each block , performance was estimated as the median execution time of correct series . Early consolidation of the trained series , assessed by the performance difference between the first block after and the last block before stimulation normalized by the r and om , was enhanced by anodal and not by sham tDCS . Stimulation did not affect r and om series execution . No stimulation effect was found on the on-line learning of the trained and new untrained series . Our results suggest that AtDCS applied on M1 soon after training improves early consolidation of procedural learning . Our data highlight the importance of neuromodulation procedures for underst and ing learning processes and support their use in the motor rehabilitation setting , focusing on the timing of the application Individuals suffering from motor impairments often require physical therapy ( PT ) to help improve their level of function . Previous investigations suggest that both intermittent theta burst stimulation ( iTBS ) and bihemispheric transcranial direct current stimulation ( tDCS ) may increase the speed and extent of motor learning/relearning . The purpose of the current study was to explore the feasibility and effectiveness of a novel , non-invasive brain stimulation approach that combined an iTBS primer , and bihemispheric stimulation coupled with motor training . We hypothesized that individuals exposed to this novel treatment would make greater functional improvements than individuals undergoing sham stimulation when tested immediately following , 24-h , and 7-days post-training . A total of 26 right-h and ed , healthy young adults were r and omly assigned to either a treatment ( n = 15 ) or control group ( n = 12 ) . iTBS ( 20 trains of 10 pulse triplets each delivered at 80 % active motor threshold ( AMT ) / 50 Hz over 191.84 s ) and bihemispheric tDCS ( 1.0 ma for 20 min ) were used as a primer to , and in conjunction with , 20 min of motor training , respectively . Our primary outcome measure was performance on the Jebsen-Taylor H and Function ( JTHF ) test . Participants tolerated the combined iTBS/bihemispheric stimulation treatment without complaint . While performance gains in the sham and stimulation group were not significant immediately after training , they were nearly significant 24-h post training ( p = 0.055 ) , and were significant at 7-days post training ( p < 0.05 ) . These results suggest that the combined iTBS/bihemispheric stimulation protocol is both feasible and effective . Future research should examine the mechanistic explanation of this approach as well as the potential of using this approach in clinical population Background This study was undertaken to test the hypothesis that a combination of excitatory anodal transcranial direct current stimulation ( tDCS ) to the contralateral motor cortex and inhibitory cathodal tDCS to the ipsilateral motor cortex of the motor performing h and ( Bi-tDCS ) would elicit more implicit motor sequence learning than anodal tDCS applied to the contralateral motor cortex alone ( Uni-tDCS ) . Methods Eleven healthy right-h and ed adults underwent a r and omized crossover experiment of Uni-tDCS , Bi-tDCS , or sham stimulation . Subjects performed a 12-digit finger sequence serial reaction time task with the right h and at baseline ( Pre ) , at immediately ( Post 1 ) , and 24 hours after stimulation ( Post 2 ) . The ratios of reaction times of predetermined repeating sequence versus r and om sequence were subjected to statistical analysis . Results The paired t test showed that reaction time ratios were significant decreased by all stimulation types at Post 1 versus Pre ( P < 0.01 ) . However , mean reaction time ratios showed a significant decrease after Uni-tDCS ( P < 0.01 ) and Bi-tDCS ( P < 0.01 ) , but only a marginal decreased after Sham ( P = 0.05 ) at Post 2 , which suggests that motor sequence learning is consoli date d by Uni-tDCS and Bi-tDCS , but only partially consoli date d by sham stimulation . No significant differences were observed between Uni-tDCS and Bi-tDCS in terms of in reaction time ratios at Post 1 or 2 . Conclusions No significant difference was found between Uni-tDCS and Bi-tDCS in terms of induced implicit motor sequence learning , but tDCS led to greater consolidation of the learned motor sequence than sham stimulation . These findings need to be tested in the context of stroke h and motor rehabilitation To test the clinical counterpart of the learned nonuse theory , 25 chronic hemiplegic stroke and head-injured patients with minimal to moderate upper extremity extensor muscle function were required to keep their uninvolved upper extremities within a h and -enclosed sling during waking hours over a 2-week interval . During this forced use period and for 1 year thereafter , changes in force or time-based measures among 21 functional tasks were compared to values at the sixth baseline session , a preintervention time when relearning had plateaued . Significant ( P less than 0.05 , Friedman 's repeated measures followed by Tukey multiple comparison tests ) changes were seen in 19 of the 21 tasks with most persisting at the 1-year follow-up . There were no apparent differences between right- and left-sided involvement or between stroke versus head injury clients ( Mann-Whitney procedure ) . Ratings for quality of movement scored from videotapes presented in r and om order showed no change over time . These data suggest that learned nonuse does occur in select neurological patients and that this behavior can be reversed through application of a forced use paradigm 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 epide \n Output:\n " }, { "from": "agent", "value": "The results indicate that application of multiple sessions of a-tDCS , compared to single session a-tDCS induced a significant improvement in skill in both SEQTAP/SRTT and SVIPT .\nRetention after a single day and multiple days of a-tDCS was statistically significant for the SEQTAP/SRTT task but not for SVIPT .\nTherefore , our findings suggest that application of M1 a-tDCS across the three or five consecutive days can be helpful to improve motor sequence learning" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: OBJECTIVE Individual differences in sensitivity to cyclical changes in ovarian steroids estradiol ( E2 ) and progesterone ( P4 ) have been implicated in the pathophysiology of menstrually related mood disorder ( MRMD ) . However , no prospect i ve studies have investigated psychosocial risk factors for sensitivity to hormone effects on mood in MRMD . Using a repeated measures approach and multilevel models , we tested the hypothesis that a history of abuse provides a context in which within-person elevations of E2 and P4 prospect ively predict daily symptoms . METHOD 66 women with prospect ively-confirmed MRMD recruited for a trial of oral contraceptives provided 1 month of baseline hormone and mood data prior to r and omization . Lifetime physical and sexual abuse experiences were assessed . Across one cycle , women completed daily measures of symptoms and provided blood sample s on 5 days across the menstrual cycle . Current E2 and P4 were centered within person ( CWP ) such that higher values represented cyclical elevations in hormones . RESULTS Rates of physical ( 27 % ) and sexual ( 29 % ) abuse were high , consistent with previous work documenting a link between trauma and MRMD . In women with a history of physical abuse , cyclical increases in P4 predicted greater mood and interpersonal symptoms on the three days following that sample . In women with a history of sexual abuse , cyclical increases in E2 predicted greater anxiety symptoms on the three days following that sample . CONCLUSIONS Results inform further inquiry into the role of severe life stressors and stress response systems in MRMD . We discuss areas for future research on the psychosocial and physiological pathways through which abuse may influence the link between hormones and symptoms The objective of this study was to evaluate whether heart rate variability ( HRV ) can be used as an index of parasympathetic reactivation after exercise . Heart rate recovery after exercise has recently been shown to have prognostic significance and has been postulated to be related to abnormal recovery of parasympathetic tone . Ten normal subjects [ 5 men and 5 women ; age 33 + /- 5 yr ( mean + /- SE ) ] exercised to their maximum capacity , and 12 subjects ( 10 men and 2 women ; age 61 + /- 10 yr ) with coronary artery disease exercised for 16 min on two separate occasions , once in the absence of atropine and once with atropine ( 0.04 mg/kg ) administered during exercise . The root mean square residual ( RMS ) , which measures the deviation of the R-R intervals from a straight line , as well as the st and ard deviation ( SD ) and the root mean square successive difference of the R-R intervals ( MSSD ) , were measured on successive 15- , 30- , and 60-s segments of a 5-min ECG obtained immediately after exercise . In recovery , the R-R interval was shorter with atropine ( P < 0.0001 ) . Without atropine , HRV , as measured by the MSSD and RMS , increased early in recovery from 4.1 + /- 0.4 and 3.7 + /- 0.4 ms in the first 15 s to 7.2 + /- 1.0 and 7.4 + /- 0.9 ms after 1 min , respectively ( P < 0.0001 ) . RMS ( range 1.7 - 2.1 ms ) and MSSD were less with atropine ( P < 0.0001 ) . RMS remained flat throughout recovery , whereas MSSD showed some decline over time from 3.0 to 2.2 ms ( P < 0.002 ) . RMS and MSSD were both directly related ( r(2 ) = 0.47 and 0.56 , respectively ; P < 0.0001 ) to parasympathetic effect , defined as the difference in R-R interval without and with atropine . In conclusion , RMS and MSSD are parameters of HRV that can be used in the postexercise recovery period as indexes of parasympathetic reactivation after exercise . These tools may improve our underst and ing of parasympathetic reactivation after exercise and the prognostic significance of heart rate recovery Estrogens are involved in the modulation of the cardiovascular system , yet their effects in young women remains largely unknown . Women who undergo ovulation induction treatments attain extremely high estrogen concentrations during a very short time period . The aim of the present study was to evaluate the effects of an acute increase in estrogens on the autonomic nervous system modulation of heart rate variability ( HRV ) . A total of 27 women undergoing ovulation induction and 14 normally menstruating women were prospect ively studied . HRV was assessed during nadir and peak estrogen using time domain and power spectral density analyses . A significant increase in high-frequency spectral power ( 243 ± 77 vs. 188 ± 73 ms2/Hz , P < 0.01 ) with a significant decrease in the ratio of low to high-frequency power was observed during estrogen peak in women undergoing induction of ovulation . The acute increase in estrogen in women undergoing ovulation induction was associated with vagal activation and altered sympathovagal balance Measuring heart rate variability ( HRV ) is a way to assess the autonomic regulation of the heart . Decreased HRV , indicating reduced parasympathetic tone , has previously been found in depression and anxiety disorders . The objective of this study was to assess HRV in women with premenstrual dysphoric disorder ( PMDD ) . To this end , time domain variables and frequency domain variables were assessed in 28 women with PMDD and in 11 symptom-free controls during both the symptomatic luteal phase and the non-symptomatic follicular phase of the menstrual cycle . Two variables reflecting vagal activity in the time domain , the root mean square of differences of successive normal RR intervals ( rMSSD ) and st and ard deviation of normal RR intervals ( SDNN ) were lower in PMDD patients , but this difference was statistically significant in the follicular phase only . The most important vagal measure in the frequency domain , supine high frequency ( HF ) , also appeared lower in PMDD subjects during the follicular phase . It is suggested that PMDD may be associated with reduced vagal tone compared to controls and that this difference is most apparent in the non-symptomatic follicular phase of the menstrual cycle Background Menstrual cycle-related symptoms are an important health issue for many women , and some may affect cardiac autonomic regulation . In the present study , we evaluated the cardiovascular and physiological stress response to 12-h short-term fasting in the menstrual phases of healthy young women . Methods We performed a r and omized crossover study . Subjects were seven female university students ( age : 22.3 ± 1.0 years ) . The experiments comprised four sessions : meal intake in the follicular phase , meal intake in the luteal phase , fasting in the follicular phase , and fasting in the luteal phase . All subjects participated in a total of four experimental sessions during two successive phases ( follicular and luteal phase in the same menstrual cycle , or luteal phase and follicular phase in the next menstrual cycle ) according to a r and omized crossover design . R-R intervals were continuously recorded before and after meals , and power spectral analysis of heart rate variability was performed . Other physiological data were obtained before and 20 , 40 , 60 , and 80 min after meal intake or after the corresponding time point of meal intake ( fasting in the follicular or luteal phase ) . Results Heart rate decreased during fasting in the follicular and luteal phases . High frequency power increased during fasting in the follicular and luteal phases . In addition , salivary cortisol concentrations decreased during fasting in the luteal phase . Conclusions In the present study , short-term fasting result ed in higher parasympathetic activity and lower cortisol levels in the luteal phase in these young women . These results indicate a possibility to produce an anti-stress effect in the luteal phase , which may reduce menstrual symptoms Background Work stress is associated with an increased risk of pre-diabetes , Type 2 diabetes , and inflammation , as well as decreased autonomic nervous system function as measured , for example , via heart rate variability . We investigated the extent to which the association between work stress and glycemic status is mediated by vagally-mediated heart rate variability ( vmHRV ) and /or inflammation . Methods Cross-sectional data from the Mannheim Industrial Cohort Study ( MICS ) with 9,937 participants were analyzed . The root mean squared successive differences ( RMSSD ) from long-term heart rate monitoring during work and night time periods was used to index vmHRV . Fasting plasma glucose and glycosylated hemoglobin were assessed to determine glycemic status . High sensitive C-reactive protein levels were observed as a measure of systemic inflammation and the Effort-Reward-Imbalance scale was used to evaluate work stress . Mediation models were adjusted for age , sex , and occupational status , and estimations were bootstrapped ( 5,000 replications ) . Results Effort-Reward-Imbalance was significantly negatively associated with RMSSD and both glycosylated hemoglobin and fasting plasma glucose during both work and night time periods . Effort-Reward-Imbalance was observed to have a significant direct effect on glycosylated hemoglobin and significant indirect effects , through RMSSD , on both glycemic measures during both time periods . Introducing C-reactive protein as a further mediator to the model did not alter the indirect effects observed . C-reactive protein , as an exclusive mediator , was observed to have smaller direct and indirect effects on the glycemic measures as compared to when Effort-Reward-Imbalance was included in the model . Conclusions Our results suggest that the association between work stress and glycemic status is partially mediated through vmHRV independent of systemic inflammation as measured by C-reactive protein . We conclude that work stress may be an additional factor that promotes development of hyperglycemic-metabolic states . If supported by prospect i ve evidence , these results may lead to new approaches for primary prevention of hyperglycemia in the workplace The purpose of this study was to investigate the effects of the ovarian hormones and the use of oral contraceptive pills ( OCP ) on cardiac vagal withdrawal at the onset of dynamic exercise . Thirty physically active women aged 19–32 years were divided into two groups : OCP users ( n = 17 ) and non-OCP users ( n = 13 ) . Participants were studied r and omly at three different phases of the menstrual cycle : early follicular ( day 3.6 ± 1.2 ; range 1–5 ) , ovulatory ( day 14.3 ± 0.8 ; range 13–16 ) and midluteal ( day 21.3 ± 0.8 ; range 20–24 ) , according to endogenous ( in non-OCP users ) or exogenous ( in OCP users ) estradiol and progesterone variations . The cardiac vagal withdrawal was represented by the cardiac vagal index ( CVI ) , which was obtained by the 4-s exercise test . Additionally , resting heart rate , systolic ( SBP ) and diastolic blood pressure ( DBP ) were obtained . The CVI was not significantly different between the three phases of the menstrual cycle in either the non-OCP users ( early follicular : 1.58 ± 0.1 ; ovulatory : 1.56 ± 0.1 ; midluteal : 1.58 ± 0.1 , P > 0.05 ) or OCP users ( early follicular : 1.47 ± 0.1 ; ovulatory : 1.49 ± 0.1 ; midluteal : 1.47 ± 0.1 , P > 0.05 ) ( mean ± SEM ) . Resting cardiovascular responses were not affected by hormonal phase or OCP use , except that the SBP was higher in the OCP users than non-OCP users in all phases of the cycle ( P < 0.05 ) . In summary , our results demonstrate that cardiac vagal withdrawal at the onset of dynamic exercise was not impacted by the menstrual cycle or OCP use in physically active women We investigated the effect of ovarian hormones and aging on breathing pattern [ pulmonary minute ventilation $ $ { \\left ( { \\dot {V}_{{{\\rm E } } } } \\right ) } $ $ ] , tidal volume ( VT ) , breathing frequency ( Fb ) , and respiratory sinus arrhythmia ( RSA ) in women . Recordings of $ $ \\dot {V}_{{{\\rm E}}}$$ and electrocardiogram ( ECG ) were obtained from 23 healthy women ( 10 premenopausal , 13 postmenopausal ) under resting , isocapnic hypoxia ( IH ) , and euoxic hypercapnia ( EH ) conditions . Premenopausal women were tested on three different days , each day corresponding to a specific phase of the menstrual cycle ( follicular , mid-cycle , and luteal ) ; postmenopausal women ( PMW ) were tested on 1 day only . On each test day , subjects were challenged with IH and EH . The order of the two tests was r and omized and separated by at least 1 hour . Due to the low Fb of several PMW , the b and limits for RSA analysis had to be adjusted . The spectral coherence between respiratory flow and ECG RR-interval was used to determine the spectral b and . Within the spectral b and , there was a consistent phase relationship between the two variables where high values of spectral coherence indicate a well-defined phase relationship between respiratory flow and RR-interval variability . The main findings in this study for RSA are fourfold . First , RSA did not change with different levels of ovarian hormones ( progesterone , ser \n Output:\n " }, { "from": "agent", "value": "In conclusion , meta-analyses indicate the presence of CVA fluctuations across the menstrual cycle ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: OBJECTIVES To report an exploratory subgroup analysis assessing the extent to which the overall benefit found in the Early Prostate Cancer program is dependent on lymph node status at r and omization . The program is ongoing , and the overall survival data are immature . The first combined analysis of the bicalutamide ( Casodex ) Early Prostate Cancer program at 3 years ' median follow-up showed that bicalutamide , 150 mg once daily , plus st and ard care ( radical prostatectomy , radiotherapy , or watchful waiting ) , significantly reduced the risk of objective progression and prostate-specific antigen ( PSA ) doubling in patients with localized/locally advanced prostate cancer . METHODS Men ( n = 8113 ) with localized/locally advanced disease received bicalutamide 150 mg or placebo once daily , plus st and ard care . The time to event data ( objective progression , PSA doubling ) was analyzed by lymph node status at r and omization . RESULTS Compared with st and ard care alone , bicalutamide significantly reduced the risk of objective progression , irrespective of lymph node status , with the most pronounced reduction in patients with N+ ( hazard ratio [ HR ] 0.29 ; 95 % confidence interval [ CI ] 0.15 to 0.56 ) compared with those with N0 ( HR 0.59 ; 95 % CI 0.48 to 0.73 ) and Nx ( HR 0.60 ; 95 % CI 0.50 to 0.72 ) disease . The largest decrease in risk of PSA doubling with bicalutamide was observed in N+ disease ( HR 0.16 ; 95 % CI 0.09 to 0.29 ) , with significantly reduced risks seen in N0 ( HR 0.45 ; 95 % CI 0.40 to 0.51 ) and Nx ( HR 0.38 ; 95 % CI 0.33 to 0.44 ) disease . CONCLUSIONS The greatest reduction in the risk of objective progression and PSA doubling with bicalutamide was seen in patients with N+ disease . However , bicalutamide also provided a statistically significant benefit in those with N0 and Nx disease PURPOSE To evaluate the effect of immediate and rogen suppression in conjunction with st and ard external beam irradiation vs. radiation alone on a group of pathologically staged lymph node-positive patients with adenocarcinoma of the prostate . METHODS AND MATERIAL S A national prospect i ve r and omized trial ( RTOG 85 - 31 ) of st and ard external beam irradiation plus immediate and rogen suppression vs. external beam irradiation alone was initiated in 1985 for patients with locally advanced adenocarcinoma of the prostate . One hundred seventy-three of the patients in this trial had biopsy-proven pathologically involved lymph nodes . Ninety-eight of these patients received radiation plus the immediate and rogen suppression ( LHRH agonist ) , while 75 received radiation alone with hormonal manipulation instituted at the time of relapse . RESULTS With a median followup of 4.9 years , estimated progression-free survival with PSA < 1.5 ng/ml at 5 years was 55 % for the patients who received radiation plus immediate LHRH agonist vs. 11 % of the patients who received radiation alone with hormonal manipulation at relapse ( p = 0.0001 ) . Because all of these patients had locally advanced disease ( i.e. , pathologically positive lymph nodes ) , stage does not explain this difference in outcome , and Gleason grade was not statistically different between the two groups . Estimated absolute survival at 5 years for the radiation and LHRH group was 73 vs. 65 % for the radiation alone group who received and rogen suppression at relapse . Estimated disease-specific survival at 5 years was 82 % for the radiation and immediate LHRH agonist group and 77 % for the radiation-alone group . CONCLUSION Patients with adenocarcinoma of the prostate and pathologically involved pelvic lymph nodes ( pN+ or clinical stage D1 ) should be seriously considered for external beam irradiation plus immediate hormonal manipulation over radiation alone with hormonal manipulation at the time of relapse Concepts regarding the surgical treatment of cancer of the prostate have changed significantly at the Mayo Clinic . Rather than emphasizing radical prostatectomy only for low- grade ( grade less than or equal to 2 ) and low-stage ( less than or equal to T1/B1 ) lesions -- which may be equally well treated at less than ten years , in regard to crude survival , by radiotherapy -- we believe that radical prostatectomy is particularly suitable for lesions of higher local stages , including those with regional node extension . This view is based on a large experience ( less than 2,000 cases ) with the radical surgical treatment of cancer of the prostate and on the realization that conservative single-modality treatment ( hormonal or radiotherapy ) for advanced local Stages ( C and D1 ) provides poor cause-specific survival and nonprogression rates and may lead to high local morbidity . The treatment of Stage D1 prostate cancer was thought to be not amenable to surgical treatment , and many have recommended observation only . In 266 patients ( mean age , 64 years ) followed one to twenty-one years ( mean , 4.7 years ) , immediate adjuvant orchiectomy at the time of radical prostatectomy performed in 162 patients ( 61 % ) result ed in a highly significant ( P less than 0.0001 ) decrease in progression compared with no immediate orchiectomy in 104 patients ( 39 % ) . The ten-year overall and local nonprogression rates for those undergoing immediate orchiectomy were 80 percent and 98 percent , respectively ; median time to progression for the no-immediate-orchiectomy group was less than 4.5 years , and the local recurrence rate was 25 percent at ten years . Of all the pathologic variables , only DNA ploidy pattern had a significant influence on progression and cause-specific survival . Also , in patients with D1 disease and a nuclear DNA diploid pattern , immediate adjuvant orchiectomy result ed in a nonprogression rate of 100 percent at ten years compared with virtually 0 percent in those with a nondiploid tumor and no immediate orchiectomy . Because 42 percent of the patients with D1 disease in the Mayo Clinic experience have DNA diploid tumors , adjuvant orchiectomy in this group results in no progression or prostate cancer death . Patients with Stage D1 prostate cancer and DNA nondiploid pattern undergoing prostatectomy should be entered in prospect i ve adjuvant innovative treatment protocol s since these tumors do not seem to respond to early hormonal manipulation PURPOSE In a r and omized study we compared the combination of orchiectomy and radiotherapy to radiotherapy alone as treatment for locally advanced prostate cancer . Patients who were treated only with radiotherapy initially underwent castration therapy at clinical progression , providing the opportunity to compare immediate vs deferred endocrine intervention . MATERIAL S AND METHODS In this prospect i ve study 91 patients with locally advanced prostate cancer were r and omized to receive external beam radiotherapy ( 46 ) or combined orchiectomy and radiotherapy ( 45 ) after surgical lymph node staging . Survival rates were calculated . RESULTS During 14 to 19 years of followup 87 % of the patients in the radiotherapy group and 76 % in the combined orchiectomy and radiotherapy group died ( log rank p = 0.03 ) . Prostate cancer mortality was 57 % and 36 % , respectively ( log rank p = 0.02 ) . The difference in favor of combined treatment was mainly caused by lymph node positive tumors . For node negative tumors there was no significant difference in the survival rates . CONCLUSIONS Immediate and rogen deprivation should be considered instead of deferred endocrine treatment started at clinical progression for prostate cancer with spread to regional lymph nodes . While awaiting evidence from r and omized trials , one should consider full dose radiotherapy for local control of locally advanced prostate cancer even when it is lymph node positive 4570 Purpose : We previously reported 7 year follow-up of men with clinical ly localized prostate cancer , who underwent radical prostatectomy ( RP ) and pelvic lymphadenectomy ( PLD ) and were found to have nodal metastases ( N+ ) , had significantly improved survival and disease-specific survival with immediate ( within 3 months of surgery ) and continuous hormonal monotherapy ( HT ) compared with those who had and rogen ablation withheld until distant metastases were identified ( NEJM 341:1781,1999 ) . To determine the durability of this effect , we up date results at 10 years median follow-up . METHODS 98 men were r and omized to receive Goserelin acetate or bilateral orchiectomy ( N=47 ) vs. observation ( N=51 ) until distant disease was documented . Patients were followed with semi-annual exams and laboratory tests , and annual bone scans . RESULTS Patients were well-matched for age ( mean 65.9 yrs ) , prostate size , local extent , and Gleason score . Only 20 % of men had detectable PSA 's following their surgery at the time of r and omization . At median follow-up of 10 years , 13 of 47 men who received immediate HT died ( 6 of prostate cancer , 7 of non-prostate cancer causes with undetectable PSA 's at the time of death ) vs 26 in the deferred arm ( 22 of prostate cancer , 4 of non-prostate cancer ) . The differences in both overall ( immediate 72.4 % ; deferred 49.0 % , p = .025 ) , and cause specific ( immediate : 87.2 % ; deferred : 56.9 % , p = .001 ) survivals , between the two arms were significant . Toxicities of treatment were tolerable , and at last follow-up , no immediately treated man had experienced an osteoporotic fracture or had discontinued HT . CONCLUSION 10 years , early HT in patients with N+ disease following RP+PLD continues to be associated with highly significant improvements in overall and disease-specific survival . The treatment has been generally well tolerated . Early HT 's role in other disease scenarios warrants testing in prospect i ve r and omized studies . No significant financial relationships to disclose 4628 Background : The Early Prostate Cancer ( EPC ) program is an ongoing study of the effect of adding bicalutamide ( CASODEX ) 150 mg to st and ard care ( radiotherapy [ RT ] , radical prostatectomy [ RP ] , or watchful waiting [ WW ] ) for men with localized or locally advanced prostate cancer . At a median 7.4 years ' follow-up , bicalutamide significantly improved objective progression-free survival ( PFS ) in men with locally advanced disease , irrespective of st and ard care , and improved overall survival in the RT setting . There was no PFS benefit in patients with localized disease . Lymph-node involvement is an established risk factor for progression , so we conducted an exploratory analysis among patients with locally advanced disease to assess the influence of this risk factor on PFS . METHODS The EPC program ( n = 8113 ) comprises 3 r and omized trials design ed for combined analysis . Patients with localized ( T1 - 2 , N0/Nx ) or locally advanced ( T3 - 4 , any N ; or any T , N+ ) non-metastatic prostate cancer received bicalutamide ( n = 4052 ) or placebo ( n = 4061 ) once daily plus st and ard care . This sub analysis studied the effect of nodal status ( N- , N+ , Nx ) in locally advanced disease . RESULTS In patients with locally advanced disease , PFS improvements were irrespective of nodal status . The treatment effect increased as the risk of progression increased from N- to Nx to N+ disease . The greatest reduction in risk was seen in RP patients with N+ disease . CONCLUSIONS The reduction in risk of progression with bicalutamide was seen irrespective of nodal status . The most significant reduction in risk of progression was in RP patients with N+ disease ; survival data by nodal status for these patients will be presented . [ Table : see text ] [ Table : see text ] BACKGROUND Appropriate timing of and rogen deprivation treatment ( ADT ) for prostate cancer is controversial . Our aim was to determine whether immediate ADT extends survival in men with node-positive prostate cancer who have undergone radical prostatectomy and pelvic lymphadenectomy compared with those who received ADT only once disease progressed . METHODS Eligible patients from 36 institutes in the USA were r and omly assigned in 1988 - 93 to receive immediate ADT ( n=47 ) or to be observed ( n=51 ) , with ADT to be given on detection of distant metastases or symptomatic recurrences . Patients were followed up every 3 months for the first year and every 6 months thereafter . The primary endpoint was progression-free survival ; secondary endpoints were overall and disease-specific survival . Analysis was by intention to treat . To ensure that the treatment groups were comparable , we did a retrospective central pathology review of slides and re grade d the Gleason scores for available sample s. This trial pre date s the requirement for clinical trial registration . FINDINGS At median follow-up of 11.9 years ( range 9.7 - 14.5 for surviving patients ) , men assigned immediate ADT had a significant improvement in overall survival ( hazard ratio 1.84 [ 95 % CI 1.01 - 3.35 ] , p=0.04 ) , prostate-cancer-specific survival ( 4.09 [ 1.76 - 9.49 ] , p=0.0004 ) , and progression-free \n Output:\n " }, { "from": "agent", "value": "Conclusions The data available suggest an improvement in survival and delayed disease progression but increased adverse events for patients with node-positive prostate cancer after local therapy treated with early and rogen suppression therapy versus deferred and rogen suppression therapy ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: We conducted a phase II study of S-1 and carboplatin combination regimen in the treatment of patients with advanced non-small cell lung cancer ( NSCLC ) . Chemotherapy-naïve patients with advanced NSCLC were treated with S-1 and carboplatin . S-1 was administered orally twice daily for 14 days and carboplatin AUC 5 on day 1 of each cycle , and this was repeated every 4 weeks . Twenty-nine patients were enrolled in this study . The main grade 3 or 4 toxicities observed during the first cycle were neutropenia ( 10.3 % ) , thrombocytopenia ( 41 % ) , and transaminase elevation . Objective responses were seen in 9 patients ( response rate 31.0 % ) . The median survival time and median progression-free survival were 16.0 months ( 95 % CI , 12.1 - 19.0 months ) and 4.5 months ( 95 % CI , 3.2 - 6.1 months ) , respectively . Hematological adverse events reaching grade 3 or 4 were neutropenia ( 10.3 % ) , anemia ( 3.4 % ) , and thrombocytopenia ( 3.4 % ) . No febrile neutropenia was detected . Nonhematological toxicities were also mild . Although grade 3 infection was observed in 1 patient , the patient improved without intervention . The combination of S-1 plus carboplatin is an active and well-tolerated regimen for the treatment of patients with advanced NSCLC . Further investigations are required to confirm our results in r and omized trials Gefitinib , an epidermal growth factor receptor tyrosine kinase inhibitor ( EGFR-TKI ) , is an effective treatment for advanced non-small cell lung cancer ( NSCLC ) in patients with activating EGFR mutations . However , there have been little evidence -based studies of gefitinib in combination with platinum-doublet therapy in these patients . We performed a phase II trial to determine the efficacy and safety of triplet chemotherapy with gefitinib , carboplatin , and S-1 as a first-line treatment . This was a multicentre , single-arm , phase II trial of carboplatin , S-1 , and gefitinib in advanced NSCLC patients with activating EGFR mutations . Patients received four courses of these drugs in 3–4 week cycles . In each cycle , carboplatin ( area under curve = 5 ) was administered on day 1 , S-1 ( 80 mg/m2 ) on days 1–14 , and gefitinib ( 250 mg ) every day . Subsequently , the same regimen without carboplatin was administered until disease progression or unacceptable toxicity occurred . The 1-year progression-free survival ( PFS ) was the primary endpoint , while response rate ( RR ) , PFS , overall survival ( OS ) , and safety were secondary endpoints . Thirty-five patients were enrolled into this study . The 1-year PFS was 74.3 % and the overall RR was 85.7 % . The median PFS for all patients was 17.6 months ( 95 % confidence interval 15.5–∞ ) , but the median OS was not reached , because 28 patients were still alive after a median follow-up time of 21.4 months . Haematological adverse events ( grade 3 or higher ) included neutropaenia ( 17.1 % ) , thrombocytopenia ( 14.3 % ) , and anaemia ( 5.7 % ) , while non-haematological adverse events ( grade 3 or higher ) included elevated aminotransferase ( 20.0 % ) , diarrhoea ( 14.3 % ) , and febrile neutropaenia ( 2.9 % ) . No interstitial lung disease or treatment-related deaths occurred . Combination chemotherapy with carboplatin , S-1 , and gefitinib is efficacious and well tolerated as a first-line treatment in advanced NSCLC patients with activating EGFR mutations A previous phase 3 trial demonstrated noninferiority in terms of overall survival for combined S‐1 ( an oral fluoropyrimidine ) and carboplatin compared with combined paclitaxel and carboplatin as first‐line treatment for advanced non – small cell lung cancer ( NSCLC ) . In the current study , the authors evaluated the efficacy and safety of combined S‐1 , carboplatin , and bevacizumab followed by maintenance with S‐1 and bevacizumab in chemotherapy‐naive patients with advanced nonsquamous NSCLC The majority of patients with completely resected stage II or IIIA non-small-cell lung cancer ( NSCLC ) require adjuvant chemotherapy to improve survival following surgery . In the present trial , the 2-year disease-free survival ( DFS ) , and the feasibility and safety of S-1 as an adjuvant chemotherapy for advanced lung cancer were evaluated . A total of 40 patients with completely resected stage II or IIIA NSCLC were enrolled and r and omized to receive postoperative chemotherapy with either up to 4 cycles of paclitaxel plus carboplatin ( arm A ) or with up to 1 year of S-1 ( arm B ) . The primary endpoint was 2-year DFS . The secondary endpoints were feasibility and toxicity . A total of 40 patients were enrolled , but 3 were excluded in accordance with the exclusion criteria . The remaining 37 patients were analyzed . The 2-year DFS rate was 54.2 % in arm A and 84.2 % in arm B. Overall , 15/18 ( 83.3 % ) patients completed 4 cycles of paclitaxel plus carboplatin and 13/19 ( 68.4 % ) completed 1-year of S-1adjuvant chemotherapy . Of the 18 ( 16.7 % ) patients in arm A , 3 experienced grade 3 or 4 adverse events , while none in arm B experienced such events . Therefore , S-1 chemotherapy for patients with completely resected stage II or IIIA NSCLC was a feasible and safe regimen , and it may therefore be considered as a potential adjuvant chemotherapy option for advanced NSCLC The objective of this phase I/II study was to determine the recommended dose ( RD ) of S-1 and carboplatin ( CBDCA ) , and to evaluate the efficacy and safety of this combination in the treatment of patients with advanced non-small cell lung cancer ( NSCLC ) . Chemotherapy-naïve patients were treated with S-1 given orally on days 1 - 14 , and CBDCA infused intravenously on day 1 , repeated every 3 weeks . RD was AUC5 of CBDCA and 80 mg/m(2 ) of S-1 . Nineteen patients were treated at the RD . The overall response was 30.8 % ( 95 % confidence interval : 17.1 - 58.3 % ) . The response rate in the RD was 36.8 % ( 95 % CI : 16.3 - 61.6 % ) . The median overall survival time was 11.1 months ( 95 % CI : 8.1 - 15.3 months ) and the median progression-free survival time was 5.0 months ( 95 % CI : 3.6 - 6.0 months ) . Major grade s 3 - 4 toxicities were thrombocytopaenia ( 47 % ) , anaemia ( 26 % ) and infection ( 16 % ) . This is the first report to show promising activity of this combination in phase II , including survival data and manageable toxicity , especially in out patients receiving treatment for advanced NSCLC PURPOSE The primary goal of this open-label , multicenter , r and omized phase III trial was to determine whether treatment with carboplatin plus the oral fluoropyrimidine derivative S-1 was noninferior versus that with carboplatin plus paclitaxel with regard to overall survival ( OS ) in chemotherapy-naive patients with advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS A total of 564 patients were r and omly assigned to receive either carboplatin ( area under the curve , 5 ) on day 1 plus oral S-1 ( 40 mg/m2 twice per day ) on days 1 to 14 or carboplatin ( area under the curve , 6 ) plus paclitaxel ( 200 mg/m2 ) on day 1 every 21 days . RESULTS At the planned interim analysis , with a total of 268 death events available , the study passed the O'Brien-Fleming boundary of 0.0080 for a positive result and noninferiority of carboplatin and S-1 compared with carboplatin and paclitaxel was confirmed for OS ( hazard ratio , 0.928 ; 99.2 % CI , 0.671 to 1.283 ) . Median OS was 15.2 months in the carboplatin and S-1 arm and 13.3 months in the carboplatin and paclitaxel arm , with 1-year survival rates of 57.3 % and 55.5 % , respectively . Rates of leukopenia or neutropenia of grade 3/4 , febrile neutropenia , alopecia , and neuropathy were more frequent in the carboplatin and paclitaxel arm , whereas thrombocytopenia , nausea , vomiting , and diarrhea were more common in the carboplatin and S-1 arm . The carboplatin and S-1 arm had significantly more dose delays than the carboplatin and paclitaxel arm . CONCLUSION Oral S-1 with carboplatin was noninferior in terms of OS compared with carboplatin and paclitaxel in patients with advanced NSCLC , and is thus a valid treatment option Background : The purpose of this study was to evaluate the feasibility and compliance of adjuvant chemotherapy of S-1 plus carboplatin for patients with completely resected non-small cell lung cancer ( NSCLC ) of pathological stage IB-IIIB . Methods : S-1 was given orally at a dose of 80 mg/m2/day for 2 weeks , followed by a 2-week period of no treatment . Carboplatin was given intravenously on day 8 at an area under the curve of 6 . This regimen was repeated for four to six 28-day courses . Results : Seventeen patients were enrolled in this study . Fourteen of them completed at least 4 cycles of chemotherapy . Nine patients had grade 2 and three patients had grade 3 thrombocytopenia , respectively . Severe nonhematologic toxicities were uncommon . Treatment was delayed in a few patients because of prolonged thrombocytopenia . Conclusion : We concluded that the regimen was feasible and tolerable for patients with completely resected NSCLC as adjuvant chemotherapy BACKGROUND A phase III study ( Lung Cancer Evaluation of TS-1 ) previously demonstrated noninferiority in terms of overall survival ( OS ) at interim analysis for carboplatin-S-1 compared with carboplatin-paclitaxel for first-line treatment of advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS A total of 564 patients were r and omly assigned to receive either carboplatin on day 1 plus oral S-1 on days 1 - 14 or carboplatin-paclitaxel on day 1 every 21 days . Up date d results and post hoc subgroup analysis according to tumor histology are presented . RESULTS The up date d analysis revealed a median OS of 15.2 months in the carboplatin-S-1 arm and 13.1 months in the carboplatin-paclitaxel arm , with a hazard ratio ( HR ) of 0.956 [ 95 % confidence interval ( CI ) 0.793 - 1.151 ] , consistent with the previous primary analysis . Median OS was 14.0 months in the carboplatin-S-1 arm and 10.6 months in the carboplatin-paclitaxel arm ( HR 0.713 ; 95 % CI 0.476 - 1.068 ) for patients with squamous cell carcinoma ( SCC ) , with corresponding values of 15.5 and 13.9 months ( HR 1.060 ; 95 % CI 0.859 - 1.308 ) for those with non-SCC . CONCLUSIONS These results establish the efficacy and safety of carboplatin-S-1 in patients with advanced NSCLC regardless of tumor histology Purpose There is no established st and ard regimen for non-small cell lung cancer ( NSCLC ) patients with interstitial lung disease ( ILD ) . For them , we performed a pilot study to evaluate the feasibility of chemotherapy with carboplatin and S-1 , which are known as cytotoxic drug with rare development of ILD as adverse event . Methods A total of 21 chemotherapy-naive NSCLC patients with ILD were prospect ively enrolled between March 2009 and September 2011 . Every 3 weeks , carboplatin at a dose of AUC 5 on day 1 and S-1 at a dose of 80 mg/m2 daily for 14 days were administered . Results The median age at initiating chemotherapy was 67 . Histological examination revealed 10 patients ( 48 % ) with adenocarcinoma . Before chemotherapy , partial pressure of arterial O2 ( PaO2 ) was low with a median of 71 Torr on room air . The median number of cycles administered was four , and the overall response rate and disease control rate were 33 and 67 % , respectively . At the time of data cut-off , all patients were deceased . The median progression-free survival ( PFS ) and median overall survival ( OS ) periods were \n Output:\n " }, { "from": "agent", "value": "Conclusion : It will provide latest evidence to determine the efficacy and safety of CS for treatment of patients with NSCLC ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: EDITORIAL COMMENT : This vignette draws attention to a detail of surgical technique familiar to all surgeons who perform the Pfannenstiel incision . Freeing the insertion of the pyramidalis muscles from the rectus sheath is often untidy and can cause considerable haemorrhage . Our literature search confirms the opinion of the review ers of this paper that nonfreeing of the lower leaf of the rectus sheath at Caesarean section is a new idea and so this brief ‘ r and omized controlled trial ’ was accepted for publication . One review er wondered if the trauma to the pyramidalis muscles often encountered at Caesarean section is due to variation in the level ( i.e. distance above pubic symphysis ) of the transverse skin incision , or variation in the anatomy of the pyramidalis muscles . Readers will accept the shorter time interval to reach the abdominal cavity with the technique described but may wonder if the time from entry of the abdomen to exit of the fetus from the uterus was affected , especially in cases of repeat Caesarean section where scar tissue might affect the ease of manipulation . One review er of this manuscript stated that the concept of not separating the rectus sheath from the underlying muscles is not entirely new since S. Joel Cohen advocated the technique in 1972 ( Joel Cohen , S. A technique of abdominal and vaginal hysterectomy based on time and motion studies . Heinemann , London 1972 , p10 ) OBJECTIVE A new technical variant of caesarean section was described a few years ago , which is characterised by blunt surgical preparation and simplified seam technique . A prospect i ve investigation compared the differences in the surgery and postoperative process as well as the rate of complications between this Misgav Ladach method and the conventional technique of Sectio . The individual postoperative well-being of the women was recorded by visual analog scales . - PATIENTS AND METHODS Women , whom realize the including criteria s ( first caesarean section , > /= 32 . week of pregnancy , one baby ) , were examined in this study over one year : 105 patients operated with the Misgav Ladach method and 67 conventionally operated patients . The patients were r and omized in a function of the first letter of the surname ( A-K : Misgav-Ladach method ; L-Z : classical technique ) . - RESULTS The surgical time from the cut to the seam was significantly shorter ( 29.8 vs. 49.3 min ; p < 0,001 ) in the Misgav Ladach group . There were no differences between the two methods in the rate of postoperative complications . The febrile morbidity was equivalent in both groups ( 7.6 % vs. 9 % ) , likewise the frequency of postoperative hematomas ( 3.8 % vs. 3 % ) . The postoperative period with consumption of analgetics was significantly longer in the group of conventionally operated patients ( 1.9 d vs. 2.4 d ; p < 0.01 ) . The postoperative presentness was estimated significantly better ( p < 0,.01 ) by the patients of the Misgav ladach group - probably caused by the significantly earlier mobilization ( p < 0.05 ) . - CONCLUSION The surgical technique described by Misgav and Ladach allows a safe execution of the caesarean section and represents an alternative to the conventional method . The duration of operation ( cut-seam-time ) was significantly shorter . The technique of less traumatising of tissue caused a significantly earlier mobilisation and a significantly shorter requirement of analgetics . The women estimated her postoperative physical condition as better The Joel-Cohen incision followed by nonclosure of pelvic and parietal peritoneum has been advocated as an alternative method to the Pfannenstiel incision with peritonealization at cesarean section . A r and omized trial was design ed to compare intra- and postoperative morbidity between the two techniques . Women to undergo a cesarean section were r and omly allocated to have either the Joel-Cohen incision with the parietal and pelvic peritoneum left open ( group 1 ) or to have the Pfannenstiel incision with both peritoneal layers sutured ( group 2 ) . The myometrium was closed with 1 - 0 polyglactin 910 suture using a continuous single-layer nonlocking technique . Patients in group 2 had the peritoneum approximated with 2 - 0 polyglactin 910 suture . The fascia was sutured with continuous 1 - 0 polyglactin 910 suture in all cases . Opening time was defined as the interval from skin incision to the opening of the uterine cavity . Febrile morbidity was defined as a temperature > or = 38 degrees C on two occasions 4 hours ( hr ) apart excluding the first postoperative day . Endometritis was defined as postpartum temperature > or = 38 degrees C on two occasions 4 hr apart , with uterine tenderness and /or foul-smelling lochia . One hundred forty-nine and 150 patients were allocated to group 1 and to group 2 , respectively . A shorter median ( range ) opening time [ 4 min ( 2 - 21 ) vs. 6 min ( 2 - 19 ) , respectively , p < 0.01 ] and a shorter median ( range ) operative time [ 30 min ( 10 - 65 ) vs. 40 min ( 20 - 110 ) , respectively , p < 0.01 ] were observed in group 1 . No difference was found in terms of intraoperative complications , proportion of patients who required transfusion , endometritis , sepsis , febrile morbidity , and urinary tract infections . A higher rate of wound infections was found in group 2 than in group 1 [ 14 of 150 ( 9.3 % ) vs. 2 of 149 ( 1.3 % ) , respectively , p < 0.01 ] . The Joel-Cohen incision without peritonealization result ed in a shorter opening and total operative time than the Pfannenstiel laparotomy with peritonealization . This was accomplished with a reduction of wound infections Design CORONIS is a pragmatic multicentre fractional factorial r and omised controlled trial and is being conducted in sites in Argentina , Chile , Ghana , India , Kenya , Pakistan and Sudan [ 1 ] . Women are eligible if they are undergoing their first or second caesarean section through a transverse abdominal incision . Five comparisons will be carried out using a 2 balanced incomplete block factorial design . Each woman is allocated THREE of the five pairs of interventions using a bespoke secure webbased r and omisation system ( with 24/7 automated backup telephone system ) hosted by the NPEU Clinical Trials Unit . The 5 pairs of interventions are : i. Blunt versus sharp abdominal entry ii . Exteriorisation of the uterus for repair versus intraabdominal repair iii . Single versus double layer closure of the uterus iv . Closure versus non-closure of the peritoneum ( pelvic and parietal ) v. Chromic catgut versus Polyglactin-910 for uterine repair Primary outcome : death or maternal infectious morbidity ( one or more of the following : antibiotic use for maternal febrile morbidity during postnatal hospital stay , antibiotic use for endometritis , wound infection or peritonitis ) or further operative procedures or blood transfusion . Sample size required : 15,000 women in total ; minimum 9,000 women per comparison pair In recent years Stark and colleagues ( 1 , 2 ) proposed the application to the cesarean section of a number of new surgical techniques adopted from various sources : the differences with respect to the traditional procedures were the Joel-Cohen methods for opening the abdomen , suturing the uterus in one layer , and non-closure of the visceral and parietal peritoneal layers . They demonstrated that this cesarean section procedure is safe , fast and has a low risk of postoperative complications in the mothers ( 2 ) and therefore this technique has been adopted in many centers . Nevertheless , the possible consequences of these changes on the short-term outcome of the newborn have never been evaluated . Cesarean section and maternal anesthesia are risk factors for the respiratory distress syndrome , transient tachypnea and respiratory depression in the newborn infants ( 3 ) and , therefore , we wanted to evaluate if a cesarean section technique presumably faster than the traditional procedure could improve the short-term outcome of the newborns Background Caesarean section is one of the most commonly performed operations on women throughout the world . Rates have increased in recent years – about 20–25 % in many developed countries . Rates in other parts of the world vary widely . A variety of surgical techniques for all elements of the caesarean section operation are in use . Many have not yet been rigorously evaluated in r and omised controlled trials , and it is not known whether any are associated with better outcomes for women and babies . Because huge numbers of women undergo caesarean section , even small differences in post-operative morbidity rates between techniques could translate into improved health for substantial numbers of women , and significant cost savings . Design CORONIS is a multicentre , fractional , factorial r and omised controlled trial and will be conducted in centres in Argentina , Ghana , India , Kenya , Pakistan and Sudan . Women are eligible if they are undergoing their first or second caesarean section through a transverse abdominal incision . Five comparisons will be carried out in one trial , using a 2 × 2 × 2 × 2 × 2 fractional factorial design . This design has rarely been used , but is appropriate for the evaluation of several procedures which will be used together in clinical practice . The interventions are : • Blunt versus sharp abdominal entry • Exteriorisation of the uterus for repair versus intra-abdominal repair • Single versus double layer closure of the uterus • Closure versus non-closure of the peritoneum ( pelvic and parietal ) • Chromic catgut versus Polyglactin-910 for uterine repair The primary outcome is death or maternal infectious morbidity ( one or more of the following : antibiotic use for maternal febrile morbidity during postnatal hospital stay , antibiotic use for endometritis , wound infection or peritonitis ) or further operative procedures ; or blood transfusion . The sample size required is 15,000 women in total ; at least 7,586 women in each comparison . Discussion Improvements in health from optimising caesarean section techniques are likely to be more significant in developing countries , because the rates of postoperative morbidity in these countries tend to be higher . More women could therefore benefit from improvements in techniques . Trial registration The CORONIS Trial is registered in the Current Controlled Trials registry . ISCRTN31089967 The ease of execution and the post-operative quality of 2 types of incision commonly performed in pelvic surgery were compared in a prospect i ve r and omised study : Pfannenstiel 's incision was used in 59 patients and Mouchel 's low transverse abdominal incision ( LTA ) in 60 patients . Results were evaluated 8 days and 3 months after the operation . There was no difference in immediate post-operative results between these two groups of patients . At the 3 month examination , hypoaesthesia of the skin was less frequent in patients who had been operated upon through the LTA incision . The authors conclude that the transmuscular incision is innocuous OBJECTIVE To compare the Pfannenstiel incision with transverse muscle‐cutting Maylard incision in women who had cesarean delivery . METHODS Patients were assigned r and omly to a Pfannenstiel or Maylard incision . Postoperative ttreatment was similar for each group . Surgical characteristics , complications , postoperative pain ( visual analog scale , analgesic use ) , and related quality of life ( 1‐ and 3‐month self‐administered question naires ) were analyzed . Abdominal wall muscle recovery was compared objective ly by dynamometer . RESULTS Fifty‐four women had a Pfannenstiel incision and 43 had the Maylard incision . There were no differences in intraoperative characteristics , postoperative morbidity , or pain . Women 's responses to the Nottingham Health Profile question naire at 1 and 3 months postoperatively and clinical and isokinetic testing for abdominal wall strength were similar between the two groups . CONCLUSION Transecting the rectus muscle was no more deleterious than the Pfannenstiel incision . There was no difference in objective ly measured abdominal wall strength OBJECTIVE The aim of the study was to evaluate the outcome of two different methods of cesarean section ( CS ) . DESIGN The study was design ed as a prospect i ve , r and omized , controlled trial . SETTING All CS were performed at the University Hospital in Uppsala , Sweden . POPULATION Fifty women admitted to hospital for a first elective CS were consecutively included in the study . They were r and omly allocated to two groups . METHODS One group was operated on by the Misgav Ladach method for CS and the other group by the Pfannenstiel method . All operations were performed by the same surgeon . MAIN OUTCOME MEASURES Duration of operation , amount of bleeding , analgesics required , scar appearance and length of hospitalization . RESULTS Operating time was significantly different between the two methods , with an average of 12.5 minutes with the Misgav Ladach method and 26 minutes with the Pfannenstiel method ( p<0.001 ) . The amount of blood loss differed significantly , with 448 ml and 608 ml respectively ( p=0.017 ) . Significantly less analgesic injections and tablets ( p=0.004 ) were needed after the Misgav Ladach method . CONCLUSION The Misgav Ladach method of CS has advantages over the Pfannenstiel method by being significantly quicker to perform , with a reduced amount of bleeding and diminished postoperative pain . The women were satisfied with the appearance of their scars . In this study no negative effects of the new operation technique were discovered Cesarean delivery may be complicated by dystocia if the incision size is in \n Output:\n " }, { "from": "agent", "value": "The Joel-Cohen incision has advantages compared with the Pfannenstiel incision .\nThese are : less fever , pain and analgesic requirements ; less blood loss ; shorter duration of surgery and hospital stay .\nThese advantages for the mother could be extrapolated to savings for the health system .\nHowever , these trials do not provide information on severe or long-term morbidity and mortality" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: & NA ; Aims of investigation : To quantify the magnitude of putative gender differences in experimental pressure pain threshold ( PPT ) , and to establish the relevance of repeated measurements to any such differences . Methods : Two separate studies were undertaken . A pressure algometer was used in both studies to assess PPT in the first dorsal interosseous muscle . Force was increased at a rate of 5 N /s . In study 1 , two measurements were taken from 240 healthy volunteers ( 120 males , 120 females ; mean age 25 years ) giving a power for statistical analysis of & bgr;=0.80 at & agr;=0.01 . In study two , 30 subjects ( 15 males , 15 females mean age 28 years ) were r and omly selected from study one . Fourteen repeated PPT measurements were recorded at seven , 10 min intervals . Mean PPT data for gender groups , from both studies , were analysed using analysis of covariance with repeated measures , and age as the covariate . Results : The mean PPT for each of the two measurements in study one showed a difference between gender of 12.2 N ( f=30.5 N , m=42.7 N ) and 12.8 N ( f=29.5 N , m=42.3 N ) , respectively , representing a difference of 28 % with females exhibiting a lower threshold . In study two , the mean difference calculated from 14 PPT repeated measurements over a 1 h period was comparable to that in study one at 12.3 N ( range 10.4–14.4 N ) again females exhibited the lower threshold . The differences in mean PPT values between gender were found to be significant in both study one , at ( P<0.0005 , F=37.8 , df=1 ) and study two ( P=0.01 , F=7.6 , df=1 ) . No significant differences were found in either study with repeated measurement ( P=0.892 and P=0.280 ) , or on the interaction of gender and repeated measurement after controlling for age ( P=0.36 and P=0.62 ) . Conclusion : Healthy females exhibited significantly lower mean PPTs in the first dorsal interosseous muscle than males , which was maintained for fourteen repeated measures within a 1 h period . This difference is likely to be above clinical ly relevant levels of change , and it has clear implication s for the use of different gender subjects in laboratory based experimental design s utilising PPT as an outcome measure Introduction We aim ed to compare subjective and objective sleep quality in tension-type headache ( TTH ) patients and to evaluate the relationship between sleep quality and pain thresholds ( PT ) in controls and TTH patients . Methods A blinded cross-sectional study where polysomnography ( PSG ) and PT ( to pressure , heat and cold ) measurements were done in 20 patients with TTH ( eight episodic ( ETTH ) and twelve chronic ( CTTH ) TTH ) and 29 healthy controls . Sleep diaries and question naires were applied . Results TTH patients had more anxiety ( p = 0.001 ) , insomnia ( p < 0.0005 ) , daytime tiredness ( p < 0.0005 ) and reduced subjective sleep quality ( p < 0.0005 ) compared to healthy controls . Sleep diaries revealed more long awakenings in TTH ( p = 0.01 ) but no total sleep-time differences . TTH patients had more slow-wave sleep ( p = 0.002 ) and less fast arousals ( p = 0.004 ) in their PSGs . CTTH subjects had lower pressure PT ( p = 0.048 ) and more daytime sleepiness than the controls ( p = 0.039 ) . Among TTH lower cold PT ( CPT ) correlated inversely with light sleep ( N1 ) ( r = −0.49 , p = 0.003 ) while slow arousals correlated inversely with headache-frequency ( r = −0.64 , p = 0.003 ) . Conclusions We hypothesize that TTH patients need more sleep than healthy controls and might be relatively sleep deprived . Inadequate sleep may also contribute to increased pain sensitivity and headache frequency in TTH Objective To evaluate interrater reliability using 5 newly trained observers in the assessment of pressure pain threshold ( PPT ) using a fixed-angle algometer . Methods The study design comprised 2 phases . Phase 1 : 5 undergraduate physical therapists were trained in algometry at a predefined angle , at a rate of 5 Newtons (N)/s , to the first dorsal interosseous muscle . Each observer then underwent a competency test of the application speed . The aim was to achieve repeated applications at 5 N/s without visual feedback from the algometer . Phase 2 : the 5 observers measured PPT of 13 healthy volunteers , at the first dorsal interosseous muscle . The sequence of observer measurements for each participant was r and omized . Mean PPT values for each observer were analyzed using repeated measures analysis of variance , intraclass correlation coefficient ( ICC2,1 ) , and st and ard error of measurement , with 95 % confidence intervals ( CIs ) . Results No significant differences between observers ' mean values were found ( P=0.094 ) , suggesting no bias . The ICC was 0.91 ( 95 % CI 0.82 , 0.97 ) . The st and ard error of measurement value was 6.27 N/cm2 ( 95 % CI 5.35 , 7.59 ) . Differences in PPT measurements of more than 17.39 N/cm2 ( 1.77 kg/cm2 ) are likely to exceed the magnitude of measurement error , and could be used to indicate true change . This margin of error is , however , somewhat larger than a previously proposed minimum clinical ly important difference in PPT of 14.71 N/cm2 ( 1.5 kg/cm2 ) . Discussion This study provides new evidence that trained observers can apply an algometer at a consistent rate and provide highly reliable measures of PPT in healthy humans , when PPT is calculated as the mean of 3 trials Background The mechanisms associating sleep and migraine are unknown . No previous polysomnographic ( PSG ) or pain-threshold ( PT ) study has compared patients with sleep-related migraine attacks ( SM ) , non-sleep related migraine attacks ( NSM ) and healthy controls . Methods We have performed a blinded , prospect i ve exploratory study with case – control design . Thirty-four healthy controls , 15 patients with SM and 18 patients with NSM had interictal PSG heat- , cold- and pressure PT ( HPT , CPT , PPT ) recordings and completed diary- and question naire on sleep and headache related aspects . Results NSM patients had more slow-wave sleep ( SWS ) and more K-bursts than SM patients ( K-bursts : p = 0.023 and SWS : p = 0.030 ) and controls ( K-bursts : p = 0.009 and SWS : 0.041 ) . NSM patients also had lower HPT and CPT than controls ( p = 0.026 and p = 0.021 ) . In addition , SM patients had more awakenings and less D-bursts than controls ( p = 0.025 and p = 0.041 ) . ConclusionS M- and NSM patients differed in objective - , but not subjective sleep quality . NSM patients had PSG findings indicating foregoing sleep deprivation . As foregoing sleep times were normal , a relative sleep deficit might explain reduced PT among NSM patients . The SM patients had signs of slightly disturbed sleep Persistent intermittent headache is a common disorder and is often accompanied by neck aching or stiffness , which could infer a cervical contribution to headache . However , the incidence of cervicogenic headache is estimated to be 14 - 18 % of all chronic headaches , highlighting the need for clear criterion of cervical musculoskeletal impairment to identify cervicogenic headache sufferers who may benefit from treatments such as manual therapy . This study examined the presence of cervical musculoskeletal impairment in 77 subjects , 27 with cervicogenic headache , 25 with migraine with aura and 25 control subjects . Assessment s included a photographic measure of posture , range of movement , cervical manual examination , pressure pain thresholds , muscle length , performance in the cranio-cervical flexion test and cervical kinaesthetic sense . The results indicated that when compared to the migraine with aura and control groups who scored similarly in the tests , the cervicogenic headache group had less range of cervical flexion/extension ( P=0.048 ) and significantly higher incidences of painful upper cervical joint dysfunction assessed by manual examination ( all P<0.05 ) and muscle tightness ( P<0.05 ) . Sternocleidomastoid normalized EMG values were higher in the latter three stages of the cranio-cervical flexion test although they failed to reach significance . There were no between group differences for other measures . A discriminant analysis revealed that manual examination could discriminate the cervicogenic headache group from the other subjects ( migraine with aura and control subjects combined ) with an 80 % sensitivity Background Quantitative sensory testing , including pressure pain threshold ( PPT ) , is seeing increased use in clinical practice . In order to facilitate clinical utility , knowledge of the properties of the tool and interpretation of results are required . Objectives This observational study used a clinical sample of people with mechanical neck pain to determine : ( 1 ) the influence of number of testing repetitions on measurement properties , ( 2 ) reliability and minimum clinical ly important difference , and ( 3 ) associations between PPT and key psychological constructs . Design This study was observational with both cross-sectional and prospect i ve elements . Methods Experienced clinicians measured PPT in patients with mechanical neck pain following a st and ardized protocol . Subcohorts also provided repeated measures and completed scales of key psychological constructs . Results The total sample was 206 participants , but not all participants provided data for all analyses . Interrater and 1-week test-retest reliability were excellent ( intraclass correlation coefficients [2,1]=.75–.95 ) . Potentially important differences in reliability and PPT scores were found when using only 1 or 2 repeated measures compared with all 3 . The PPT over a distal location ( tibialis anterior muscle ) was not adequately responsive in this sample , but the local site ( upper trapezius muscle ) was responsive and may be useful as part of a protocol to evaluate clinical change . Sensitivity values ( range=0.08–0.50 ) and specificity values ( range=0.82–0.97 ) for a range of change scores are presented . Depression , catastrophizing , and kinesiophobia were able to explain small but statistically significant variance in local PPT ( 3.9%–5.9 % ) , but only catastrophizing and kinesiophobia explained significant variance in the distal PPT ( 3.6 % and 2.9 % , respectively ) . Limitations Limitations of the study include multiple raters , unknown recruitment rates , and unknown measurement properties at sites other than those tested here . Conclusions The results suggest that PPT is adequately reliable and that 3 measurements should be taken to maximize measurement properties . The variance explained by the psychological variables was small but significant for 3 constructs related to catastrophizing , depression , and fear of movement . Clinical implication s for application and interpretation of PPT are discussed \n Output:\n " }, { "from": "agent", "value": "Most studies found no association between PPT values and headache characteristics such as frequency , duration or intensity ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: This study evaluated the effects of a water exercise training program that includes perturbation exercises ( WEP ) to improve the speed of voluntary stepping reaction in older adults . Speed of voluntary stepping considered as an important skill to prevent a fall when balance is lost . In a single-blinded r and omized controlled trial with a crossover design thirty-six independent old adults ( 64 - 88 years old ) were divided into two groups . Group A received WEP for the first 12 weeks , followed by no intervention for the second 12 weeks . Group B did not receive intervention for the first 12 weeks and received WEP for the second 12 weeks . Voluntary Step Execution Test and postural stability in upright st and ing ( eyes open and closed conditions ) were measured at baseline , 12 weeks , and 24 weeks . A significant interaction effect between group and time was found for the step execution , due to improvement in initiation phase and swing phase duration s in the WEP group . Also significant improvement in postural stability parameters in eyes open and closed conditions is noted . The present results indicate that the primary benefit of WEP that include perturbations to induce stepping , was a reduction in voluntary stepping times . The WEP generalized to a better control of balance in up-right st and ing This study compared the effects of 2 types of water exercise programs on balance ability in the elderly . Thirty healthy elderly persons ( 60.7 + /- 4.1 yr ) were r and omly assigned to a deep-water-running exercise ( DWRE , n = 15 ) group or a normal water exercise ( NWE , n = 15 ) group . The participants completed a twice-weekly water exercise intervention for 12 wk . Exercise sessions comprised a 10-min warm-up on l and , 20 min of water-walking exercise , 30 min of water exercise while separated into NWE and DWRE , a 10-min rest on l and , and 10 min of recreation and relaxation in water . Postural-sway distance and t and em-walking time were decreased significantly in DWRE . Postural-sway area was decreased significantly in NWE . In both groups , simple reaction times were significantly decreased . The findings of this study show that a water exercise program including deep-water running is much better than normal water exercise for improving dynamic balance ability in the elderly BACKGROUND Recently , several studies have reported age-associated increases in muscle coactivation during postural control . A rigid posture induced by strong muscle coactivation reduces the degree of freedom to be organized by the postural control system . The purpose of this study was to clarify the effect of balance training on muscle coactivation during postural control in older adults . METHODS Forty-eight subjects were r and omized into an intervention ( mean age : 81.0 ± 6.9 years ) and a control group ( mean age : 81.6 ± 6.4 years ) . The control group did not receive any intervention . Postural control ability ( postural sway during quiet st and ing , functional reach , and functional stability boundary ) was assessed before and after the intervention . A cocontraction index was measured during the postural control tasks to assess muscle coactivation . RESULTS Cocontraction index values in the intervention group significantly decreased following the intervention phase for functional reach ( p < .0125 ) . Cocontraction index values had a tendency to decrease during functional stability boundary for forward and quiet st and ing tasks . Functional improvements were observed in some of the tasks after the intervention , that is , functional reach , functional stability boundary for forward , one-leg stance , and timed up and go ( p < .05 ) . CONCLUSIONS Our study raised the possibility that balance training for older adults was associated with decreases in muscle coactivation during postural control . Postural control exercise could potentially lead older adults to develop more efficient postural control strategies without increasing muscle coactivation . Further research is needed to clarify in greater detail the effects of changes in muscle coactivation The changes in postural control in elderly people after an 8-week training course were characterized . Static postural stability was measured during st and ing on a single force platform first with the eyes open and then with the eyes closed . Body sway was analysed on a force plate in groups of elderly and of young subjects . Half of the elderly subjects then took part in the training course . The posturographic measurements were repeated after the course . The sway in anteroposterior ( AP ) and mediolateral ( ML ) directions was subjected to spectral analysis . The frequency spectrum of the platform oscillations was calculated by fast Fourier transformation in the intervals 0.1–0.3 , 0.3–1 and 1–3 Hz . It was found that the sway path was longer and the frequency power was higher in the elderly group . The training caused a significant improvement in functional performance , but a significantly longer sway path was observed after the training in the ML direction . The frequency analysis revealed a significantly higher power after 8 weeks without visual control in the ML direction in the training group in the low and the middle frequency b and s. The results suggest that the participants ’ balance confidence and the control of ML balance improved in response to the training . The higher ML frequency power exhibited after the training may be indicative of a better balance performance . Thus , the increase in the sway path in this age group did not mean a further impairment of the postural control OBJECTIVE To compare the effect of a custom- design ed yoga program with 2 other balance training programs . DESIGN R and omized controlled trial . SETTING Research laboratory . PARTICIPANTS A group of older adults ( N=39 ; mean age , 74.15 ± 6.99 y ) with a history of falling . INTERVENTIONS Three different exercise interventions ( Tai Chi , st and ard balance training , yoga ) were given for 12 weeks . MAIN OUTCOME MEASURES Balance performance was examined during pre- and posttest using field tests , including the 8-foot up- and -go test , 1-leg stance , functional reach , and usual and maximal walking speed . The static and dynamic balances were also assessed by postural sway and dynamic posturography , respectively . RESULTS Training produced significant improvements in all field tests ( P<.005 ) , but group difference and time × group interaction were not detected . For postural sway , significant decreases in the area of the center of pressure with eyes open ( P=.001 ) and eyes closed ( P=.002 ) were detected after training . For eyes open , maximum medial-lateral velocity significantly decreased for the sample ( P=.013 ) . For eyes closed , medial-lateral displacement decreased for Tai Chi ( P<.01 ) . For dynamic posturography , significant improvements in overall score ( P=.001 ) , time on the test ( P=.006 ) , and 2 linear measures in lateral ( P=.001 ) and anterior-posterior ( P<.001 ) directions were seen for the sample . CONCLUSIONS Yoga was as effective as Tai Chi and st and ard balance training for improving postural stability and may offer an alternative to more traditional programs BACKGROUND Diabetes is the most common cause of peripheral neuropathies . No definitive treatment for diabetic neuropathies has been reported , and very few studies have been published on the role of exercise in reducing either the symptoms or incidence of diabetic neuropathies . METHODS This study assessed the effects of an exercise program on balance and trunk proprioception in older adults with diabetic neuropathies . Thirty-eight patients with diabetes having peripheral neuropathies were enrolled , r and omized , and subdivided in two groups : an experimental group of 19 participants with diabetes ( 72.9 ± 5.6 years old ) and a control group of 19 participants with diabetes ( 73.2 ± 5.4 years old ) . Both groups received health education on diabetes for 50 min/week for 8 weeks . The experimental group practice d an additional balance exercise program for 60 min , two times a week . The exercise training was performed two times per week for 8 weeks . Results were evaluated by both static and dynamic balance and trunk proprioception . RESULTS Postural sway significantly decreased ( P < 0.05 ) , the one-leg stance test significantly increased ( P < 0.05 ) , and dynamic balance from the Berg Balance Scale , Functional Reach Test , Timed Up and Go test , and 10-m walking time improved significantly after balance exercise ( P < 0.05 ) . Trunk repositioning errors also decreased with training ( P < 0.05 ) . CONCLUSION The balance exercise program improved balance and trunk proprioception . These results suggested that a balance exercise is suitable for individuals with diabetic neuropathy OBJECTIVE To determine whether a 12-week whole-body vibration ( WBV ) training program improved balance in participants with type 2 diabetes mellitus ( T2DM ) . DESIGN R and omized controlled trial . SETTING Primary health care setting . PARTICIPANTS Participants with T2DM ( N=50 ) . INTERVENTIONS Participants were r and omly allocated to either a WBV group ( n=25 ) , which performed a 12-week WBV-based exercise program on an oscillating platform ( 12 - 16Hz-4 mm ; 3 sessions/wk ) , or a usual-care control group ( n=25 ) . MAIN OUTCOME MEASURES Clinical and sociodemographic variables were recorded at baseline . Static balance and dynamic balance were also assessed at baseline by measuring postural sway ( measurement of center of pressure [ COP ] excursions in the anteroposterior and mediolateral directions ) using a Wii Balance Board and the Timed Up and Go test . RESULTS Significant between-group differences in COP excursions with participants ' eyes closed were found with their feet apart and feet together . In addition , participants in the WBV group exhibited significantly lower COP excursions with their eyes closed after the intervention , while participants in the control group experienced a nonsignificant deterioration in COP excursions ( ie , greater excursion ) with their eyes open ( mediolateral axis ) . There was no significant difference in the Timed Up and Go test values postintervention . CONCLUSIONS WBV provides a safe and well-tolerated approach to improve balance in participants with T2DM . These findings may have important implication s for falls prevention in those with T2DM in the primary health care setting Purpose The purpose of the study was to evaluate the effect of BodyBalance ® training on balance , functional task performance , fear of falling , and health-related quality of life in adults aged over 55 years . Participants and methods A total of 28 healthy , active adults aged 66±5 years completed the r and omized controlled trial . Balance , functional task performance , fear of falling , and self-reported quality of life were assessed at baseline and after 12 weeks . Participants either undertook two sessions of BodyBalance per week for 12 weeks ( n=15 ) or continued with their normal activities ( n=13 ) . Results Significant group-by-time interactions were found for the timed up and go ( P=0.038 ) , 30-second chair st and ( P=0.037 ) , and mediolateral center-of-pressure range in narrow stance with eyes closed ( P=0.017 ) . There were no significant effects on fear of falling or self-reported quality of life . Conclusion Twelve weeks of BodyBalance training is effective at improving certain balance and functional based tasks in healthy older adults OBJECTIVE To compare the impacts of Tai Chi , a st and ard balance exercise program , and a video game balance board program on postural control and perceived falls risk . DESIGN R and omized controlled trial . SETTING Research laboratory . PARTICIPANTS Independent seniors ( N=40 ; 72.5±8.40 ) began the training , 27 completed . INTERVENTIONS Tai Chi , a st and ard balance exercise program , and a video game balance board program . MAIN OUTCOME MEASURES The following were used as measures : Timed Up & Go , One-Leg Stance , functional reach , Tinetti Performance Oriented Mobility Assessment , force plate center of pressure ( COP ) and time to boundary , dynamic posturography ( DP ) , Falls Risk for Older People-Community Setting , and Falls Efficacy Scale . RESULTS No significant differences were seen between groups for any outcome measures at baseline , nor were significant time or group × time differences for any field test or question naire . No group × time differences were seen for any COP measures ; however , significant time differences were seen for total COP , 3 of 4 anterior/posterior displacement and both velocity , and 1 displacement and 1 velocity medial/lateral measure across time for the entire sample . For DP , significant improvements in the overall score ( dynamic movement analysis score ) , and in 2 of the 3 linear and angular measures were seen for the sample . CONCLUSIONS The video game balance board program , which can be performed at home , was as effective as Tai Chi and the st and ard balance exercise program in improving postural control and balance dictated by the force plate postural sway and DP measures . This finding may have implication s for exercise adherence because the at-home nature of the intervention eliminates many obstacles to exercise training BACKGROUND AND PURPOSE Loss of lower-extremity strength increases the risk of falls in older persons . The purpose of this study was to test the hypothesis that a vigorous program of lower-extremity strengthening , walking , and postural control exercises would improve the single-stance balance of healthy older women and lower their risk of falls and fall-associated injuries . SUBJECTS From a total of 38 respondents , 21 women were r and omly assigned to either a treatment group ( combined training , n = 12 ) or a control group ( flexibility training , n = 9 ) . The subjects ranged in age from 62 to 75 years ( mean = 68 , SD = 3.5 ) . METHODS A r and omized control trial compared the effects of two exercise programs on static balance . The combined training group exercised three times per week on knee extension and sitting leg press machines , walked briskly for 20 minutes , and performed postural control exercises , which included simple tai chi movements . The flexibility training group performed postural control exercises weekly . Measurements of balance were obtained on a force platform in double and single stance , at baseline and following 6 months \n Output:\n " }, { "from": "agent", "value": "In contrast , neither resistance nor multi-component exercise interventions affected any of the included COP measurements .\nConclusions Postural control is improved by balance exercise interventions .\nIn contrast , strength or multi-component exercise interventions did not influence postural control measurements in older adults ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: PURPOSE We identify risk factors for pathological progression among men on active surveillance in the REDEEM ( REduction by Dutasteride of clinical progression Events in Expectant Management trial ) . MATERIAL S AND METHODS REDEEM was a 3-year , r and omized , double-blind study of patients in 65 North American academic centers . Eligible men were 48 to 82 years old , with low risk prostate cancer ( T1c-T2a ) , Gleason score 6 or less , 3 or fewer cores positive , tumor less than 50 % of any 1 core , serum prostate specific antigen 11 ng/ml or less , life expectancy greater than 5 years and undergoing active surveillance . Entry biopsies ( 10 cores or more ) were required . The analysis included 276 patients with 1 biopsy or more after the start of study treatment . Patients received dutasteride 0.5 mg per day or placebo for 3 years . Time to pathological progression ( volume [ 4 or more cores positive or 50 % or greater of 1 core ] or grade progression [ Gleason score 7 or greater ] ) in a post-baseline biopsy ( not preceded by therapeutic intervention ) , and baseline variables were analyzed using a Cox proportional hazard model . RESULTS In total 94 of 276 patients with a post-baseline biopsy ( 34.1 % ) had pathological progression , 54 ( 19.6 % ) had volume progression only , 19 ( 6.9 % ) had grade progression only and 21 ( 7.6 % ) had both types of progression . Older age ( HR 1.05 , 95 % CI 1.01 - 1.08 , p=0.009 ) and higher prostate specific antigen density ( HR 1.06 , 95 % CI 1.04 - 1.09 , p<0.001 ) were associated with pathological progression . Post-baseline prostate specific antigen identified grade , but not volume progression in patients treated with placebo and dutasteride . CONCLUSIONS Older age and higher prostate specific antigen density were independent predictors of pathological progression . Post-baseline measurements as predictors of pathological progression could not be established . Further studies are needed to evaluate the role of dutasteride and establish better markers of pathological progression in active surveillance OBJECTIVE Selection criteria for active surveillance ( AS ) program of localized prostate cancer remain to be st and ardized . The purpose was to evaluate the validity of selection criteria and investigate the feasibility of this AS program . METHODS Patients meeting the criteria ( i ) stage T1cN0M0 , ( ii ) age 50 - 80 , ( iii ) serum prostate-specific antigen ( PSA ) < /=20 ng/ml , ( iv ) one or two positive cores per 6 - 12 systematic biopsy cores , ( v ) Gleason score < /=6 , and ( vi ) cancer involvement in positive core < /=50 % were enrolled and encouraged to start AS for at least 6 months during the period between January 2002 and December 2003 . PSA was measured bimonthly for 6 months and every 3 months thereafter . Trigger of treatment recommendation was PSA-doubling time ( PSADT ) of < /=2 years or pathological progression at re-biopsy . Primary endpoint was ' % PSADT > 2y ' , which was defined as the proportion of patients who showed PSADT assessed at 6 months > 2 years out of all the patients who chose AS . Point estimate of ' % PSADT > 2y ' was expected to be > 80 % . RESULTS One hundred and eighteen patients opted for AS and 16 chose immediate treatment at enrollment . PSADT for the initial 6 months based on four measurements could be assessed in 106 patients . Intent-to-treat analysis of ' % PSADT > 2y ' was 71.2 % ( 84/118 , 95 % CI : 62.1 - 79.2 ) . Pathological progression rate at 1-year re-biopsy was 33 % . Fifty-four ( 46 % ) patients remained on AS for maximal observation of 54 months . General health-related QOL in patients undergoing AS was not impaired . CONCLUSIONS The primary endpoint , ' % PSADT > 2y ' , did not meet the pre-specified decision criteria . Further prospect i ve study with revised program and endpoint is needed BACKGROUND In 2008 , we reported that radical prostatectomy , as compared with watchful waiting , reduces the rate of death from prostate cancer . After an additional 3 years of follow-up , we now report estimated 15-year results . METHODS From October 1989 through February 1999 , we r and omly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy . Follow-up was complete through December 2009 , with histopathological review of biopsy and radical-prostatectomy specimens and blinded evaluation of causes of death . Relative risks , with 95 % confidence intervals , were estimated with the use of a Cox proportional-hazards model . RESULTS During a median of 12.8 years , 166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group died ( P=0.007 ) . In the case of 55 men assigned to surgery and 81 men assigned to watchful waiting , death was due to prostate cancer . This yielded a cumulative incidence of death from prostate cancer at 15 years of 14.6 % and 20.7 % , respectively ( a difference of 6.1 percentage points ; 95 % confidence interval [ CI ] , 0.2 to 12.0 ) , and a relative risk with surgery of 0.62 ( 95 % CI , 0.44 to 0.87 ; P=0.01 ) . The survival benefit was similar before and after 9 years of follow-up , was observed also among men with low-risk prostate cancer , and was confined to men younger than 65 years of age . The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age . Among men who underwent radical prostatectomy , those with extracapsular tumor growth had a risk of death from prostate cancer that was 7 times that of men without extracapsular tumor growth ( relative risk , 6.9 ; 95 % CI , 2.6 to 18.4 ) . CONCLUSIONS Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer . Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment . ( Funded by the Swedish Cancer Society and the National Institutes of Health . ) PURPOSE We assessed risk stratification in patients with low grade prostate cancer managed by active surveillance using a 20-core saturation biopsy technique . MATERIAL S AND METHODS A total of 135 consecutive patients with low risk prostate cancer were prospect ively entered in an active surveillance program in a 10-year period . The study entrance requirement and progression definition followed Epstein criteria using only pathological parameters , ie fewer than 3 positive cores , Gleason score 6 or less and 50 % or less of any single core involved . All patients were monitored by restaging 20-core saturation biopsy every 12 to 18 months . A total of 120 patients with at least 1 rebiopsy form the basis of this report . RESULTS Of the cohort 30 % progressed during a median of 2.4 years . Three multivariate analyses were performed . The first analysis used variables only at diagnosis biopsy and revealed that prostate specific antigen density greater than 0.08 ng/ml/cc and prostate cancer family history were significant predictors of progression . When combined in a 3-level risk factor score , they were significant ( p = 0.003 ) . The second multivariate analysis considered changes in characteristics between diagnosis biopsy and first rebiopsy . Prostate specific antigen velocity along with prostate specific antigen density and family history highly predicted progression according to a 4-level risk factor score ( p < 0.0001 ) . The third multivariate analysis vali date d the previously reported prostate specific antigen density cutoff of 0.08 ng/ml/cc at first rebiopsy as a significant predictor of subsequent progression ( HR 3.16 , 95 % CI 1.12 , 8.93 ; p = 0.03 ) . CONCLUSIONS Risk factor stratification can be used to significantly predict the outcome in patients on active surveillance . Prostate specific antigen density 0.08 ng/ml/cc at first rebiopsy was vali date d as a significant predictor of subsequent progression BACKGROUND We sought to identify determinants of health-related quality of life after primary treatment of prostate cancer and to measure the effects of such determinants on satisfaction with the outcome of treatment in patients and their spouses or partners . METHODS We prospect ively measured outcomes reported by 1201 patients and 625 spouses or partners at multiple centers before and after radical prostatectomy , brachytherapy , or external-beam radiotherapy . We evaluated factors that were associated with changes in quality of life within study groups and determined the effects on satisfaction with the treatment outcome . RESULTS Adjuvant hormone therapy was associated with worse outcomes across multiple quality -of-life domains among patients receiving brachytherapy or radiotherapy . Patients in the brachytherapy group reported having long-lasting urinary irritation , bowel and sexual symptoms , and transient problems with vitality or hormonal function . Adverse effects of prostatectomy on sexual function were mitigated by nerve-sparing procedures . After prostatectomy , urinary incontinence was observed , but urinary irritation and obstruction improved , particularly in patients with large prostates . No treatment-related deaths occurred ; serious adverse events were rare . Treatment-related symptoms were exacerbated by obesity , a large prostate size , a high prostate-specific antigen score , and older age . Black patients reported lower satisfaction with the degree of overall treatment outcomes . Changes in quality of life were significantly associated with the degree of outcome satisfaction among patients and their spouses or partners . CONCLUSIONS Each prostate-cancer treatment was associated with a distinct pattern of change in quality -of-life domains related to urinary , sexual , bowel , and hormonal function . These changes influenced satisfaction with treatment outcomes among patients and their spouses or partners Abstract Introduction Active surveillance ( AS ) is a management strategy for addressing the widely acknowledged problem of over diagnosis and over treatment of clinical ly indolent prostate cancer . Methods A total of 80 patients were enrolled on the AS program in our institution between January 2008 and June 2012 . All data were collected prospect ively in a secure data base . Results The mean age of patients enrolled was 62.7 years ( range 50–72 ) . Median PSA at enrolment was 5.6 ng/mL ( range 1.2–13.4 ) . The mean follow-up was 32 months ( range 2–54 ) . In total , 85 % of patients had a repeat biopsy after 1-year with 30 % having another biopsy after 3 years . Overall , 45 % of patients remain on AS . In the remainder ; 42.5 % of patients have been removed from AS for definitive treatment , while 8.75 % of patients are now on watchful waiting , 2.5 % of patients self discharged from the program and one patient died of cardiovascular disease . The prostate cancer specific survival rate is 100 % . Reasons for removal from AS and referral for treatment were ; 67.6 % of patients had up grade of disease on repeat biopsy , 17.6 % of patients had PSA progression , 11.8 % patients had progression of disease on MRI , and one patient developed a palpable nodule . Regarding definitive treatment ; 52.9 % of patients have been for referred for external beam radiotherapy , 14.7 % have been referred for brachytherapy , 29.4 % have been referred for surgery and one patient has refused definitive treatment . Conclusion Our findings to date support active surveillance as a valid strategy for early , localised prostate cancer Study Type – Diagnostic ( exploratory cohort ) PURPOSE We assessed the feasibility of a watchful waiting protocol with selective delayed intervention using clinical , prostate specific antigen ( PSA ) or histological progression as treatment indications for clinical ly localized prostate cancer . MATERIAL S AND METHODS In this prospect i ve , single arm cohort study patients with favorable clinical parameters ( stage T1b to T2b N0M0 , Gleason score 7 or less and PSA 15 ng./ml . or less ) are conservatively treated with watchful waiting . When a patient meets disease progression criteria , arbitrarily defined by the 3 parameters of the rate of PSA increase , clinical progression or histological up grade on repeat prostate biopsy , appropriate treatment is implemented . Patients are followed every 3 months for the first 2 years and every 6 months thereafter . Serum PSA measurement and digital rectal examination are done at each visit and repeat prostate biopsy is performed 18 months after study enrollment . RESULTS Since November 1995 , the study has accrued 206 patients with a median followup of 29 months ( range 2 to 66 ) . Of these men 137 remain on the surveillance protocol with no disease progression , while 69 were withdrawn from study for various reasons . There was clinical , PSA and histological progression in 16 , 15 and 5 cases , respectively . The estimated actuarial probability of remaining on the surveillance protocol was 67 % at 2 years and 48 % at 4 . The probability of remaining progression-free was 81 % and 67 % at 2 and 4 years , respectively . CONCLUSIONS A policy of watch \n Output:\n " }, { "from": "agent", "value": "There was evidence that studies including men with the lowest risk disease and scheduled rebiopsy had higher rates of radical treatment" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Background The use of manipulation has long been advocated in the treatment of chronic obstructive pulmonary disease ( COPD ) , but few r and omized controlled clinical trials have measured the effect of manipulation on pulmonary function . In addition , the effects of individual manipulative techniques on the pulmonary system are poorly understood . Therefore , the purpose of this study was to determine the immediate effects of four osteopathic techniques on pulmonary function measures in persons with COPD relative to a minimal-touch control protocol . Methods Persons with COPD aged 50 and over were recruited for the study . Subjects received five , single-technique treatment sessions : minimal-touch control , thoracic lymphatic pump ( TLP ) with activation , TLP without activation , rib raising , and myofascial release . There was a 4-week washout period between sessions . Protocol s were given in r and om order until all five techniques had been administered . Pulmonary function measures were obtained at baseline and 30-minutes posttreatment . For the actual pulmonary function measures and percent predicted values , Wilcoxon signed rank tests were used to test within-technique changes from baseline . For the percent change from baseline , Friedman tests were used to test for between-technique differences . Results Twenty-five subjects were enrolled in the study . All four tested osteopathic techniques were associated with adverse posttreatment changes in pulmonary function measures ; however , different techniques changed different measures . TLP with activation increased posttreatment residual volume compared to baseline , while TLP without activation did not . Side effects were mild , mostly posttreatment chest wall soreness . Surprisingly , the majority of subjects believed they could breathe better after receiving osteopathic manipulation . Conclusion In persons with COPD , TLP with activation , TLP without activation , rib raising , and myofascial release mildly worsened pulmonary function measures immediately posttreatment relative to baseline measurements . The activation component of the TLP technique appears to increase posttreatment residual volume . Despite adverse changes in pulmonary function measures , persons with COPD subjectively reported they benefited from osteopathic manipulation Background Patients with COPD present a major recruitment of the inspiratory muscles , predisposing to chest incoordination , increasing the degree of dyspnea and impairing their exercise capacity . Stretching techniques could decrease the respiratory muscle activity and improve their contractile capacity ; however , the systemic effects of stretching remain unknown . Objective The aim of this study was to evaluate the effects of aerobic training combined with respiratory muscle stretching on functional exercise capacity and thoracoabdominal kinematics in patients with COPD . Design This study was a r and omized and controlled trial . Participants A total of 30 patients were allocated to a treatment group ( TG ) or a control group ( CG ; n=15 , each group ) . Intervention The TG was engaged in respiratory muscle stretching and the CG in upper and lower limb muscle stretching . Both groups performed 24 sessions ( twice a week , 12 weeks ) of aerobic training . Evaluations Functional exercise capacity ( 6-minute walk test ) , thoracoabdominal kinematics ( optoelectronic plethysmography ) , and respiratory muscle activity ( surface electromyography ) were evaluated during exercise . Analysis of covariance was used to compare the groups at a significance level of 5 % . Results After the intervention , the TG showed improved abdominal ( ABD ) contribution , compartmental volume , mobility , and functional exercise capacity with decreased dyspnea when compared with the CG ( P<0.01 ) . The TG also showed a decreased respiratory muscle effort required to obtain the same pulmonary volume compared to the CG ( P<0.001 ) . Conclusion Our results suggest that aerobic training combined with respiratory muscle stretching increases the functional exercise capacity with decreased dyspnea in patients with COPD . These effects are associated with an increased efficacy of the respiratory muscles and participation of the ABD compartment Background Manual therapists typically advocate the need for a detailed clinical examination to decide which vertebral level should be manipulated in patients with low back pain . However , it is unclear whether spinal manipulation needs to be specific to a vertebral level . Objective The purpose of this study was to analyze the immediate effects of a single , region-specific spinal manipulation defined during the clinical examination versus a single non – region-specific spinal manipulation ( applied on an upper thoracic vertebra ) in patients with chronic nonspecific low back pain for the outcome measures of pain intensity and pressure pain threshold at the time of the assessment . Design This was a 2-arm , prospect ively registered , r and omized controlled trial with a blinded assessor . Setting The study was conducted in an outpatient physical therapy clinic in Brazil . Patients The study participants were 148 patients with chronic nonspecific low back pain ( with pain duration of at least 12 weeks ) . R and omization The r and omization schedule was generated by an independent statistician and was concealed by using consecutively numbered , sealed , opaque envelopes . Interventions A single high-velocity manipulation was administered to the upper thoracic region of the participants allocated to the non – region-specific manipulation group and to the painful lumbar levels of the participants allocated to the region-specific manipulation group . Measurements Pain intensity was measured by a 0 to 10 numeric pain rating scale . Pressure pain threshold was measured using a pressure algometer . Limitations It was not possible to blind the therapist and participants . Results A total of 148 patients participated in the study ( 74 in each group ) . There was no loss to follow-up . Both groups improved in terms of immediate decrease of pain intensity ; however , no between-group differences were observed . The between-group difference for pain intensity and pressure pain threshold were 0.50 points ( 95 % confidence interval=−0.10 to 1.10 ) and −1.78 points ( 95 % confidence interval=−6.40 to 2.82 ) , respectively . No adverse reactions were observed . Conclusion The immediate changes in pain intensity and pressure pain threshold after a single high-velocity manipulation do not differ by region-specific versus non – region-specific manipulation techniques in patients with chronic low back pain CONTEXT Osteopathic manipulative treatment ( OMT ) has long been advocated for patients with respiratory disorders , but little definitive evidence exists to support its use in this population . OBJECTIVE To investigate the immediate effect of OMT on pulmonary function parameters in elderly subjects with chronic obstructive pulmonary disease . METHODS Subjects aged 65 years or older with a forced expiratory volume in 1 second to forced vital capacity ratio of less than 70 % were recruited and r and omly assigned to receive either OMT or sham therapy . The OMT protocol consisted of seven st and ardized osteopathic manipulative techniques , while the sham therapy protocol comprised light touch applied to the same anatomic regions and for the same duration ( 20 min ) . All subjects received baseline and posttreatment pulmonary function testing . A telephone survey was conducted 1 day after the intervention to collect subjective feedback and assess the success of blinding protocol s. RESULTS Of the 35 study participants , 18 were r and omly assigned to the OMT group and 17 to the sham group . Compared with the sham group , the OMT group showed a statistically significant decrease in the forced expiratory flow at 25 % and 50 % of vital capacity and at the midexpiratory phase ; the expiratory reserve volume ; and airway resistance . The OMT group also had a statistically significant increase in the residual volume , total lung capacity , and the ratio of those values compared with the sham group . Most subjects ( 82 % , OMT group ; 65 % , sham group ) reported breathing better after receiving their treatment . Only 53 % of subjects in the OMT group and 41 % in the sham group correctly guessed their group assignment . CONCLUSION Results suggest an overall worsening of air trapping during the 30 minutes immediately following one multitechnique OMT session relative to the sham group OBJECTIVE The purpose of this preliminary study was to demonstrate the feasibility of a study that measures the short-term effects of a course of manual therapy ( MT ) and exercise ( Ex ) in people with moderate chronic obstructive pulmonary disease ( COPD ) . METHODS Fifteen participants ( 9 males ; mean age , 56.1 years ) , with moderate COPD ( mean % predicted forced expiratory volume in the first second [ FEV1 % predicted ] , 61.8 % ) , were r and omly allocated to 1 of 3 groups : soft tissue therapy only ( ST ) ; ST and spinal manipulation ( SM ) ; or ST , SM , and Ex . The intervention continued for 4 weeks . Outcome measures included FEV1 , forced vital capacity ( FVC ) , chronic respiratory question naire ( CRQ-SAS ) scores , distance walked in a 6-minute walking test , and monitoring for adverse events . RESULTS There was an increase in FVC for the SM + ST + Ex group compared with ST only and ST + SM ( 1.01 and 1.00 L , respectively ) . Distance walked increased in the ST + SM and ST + SM + Ex groups compared with ST only ( 120.0 and 168.0 m , respectively ) . Dyspnea levels decreased in the ST + SM and ST + SM + Ex groups compared with ST only ( 0.64 and 0.44 , respectively ) . There were no major or moderate adverse events reported following ST or SM interventions . CONCLUSIONS For this small group of patients , combining MT with Ex produced short improvements in FVC , distance walked , and dyspnea levels , with no major or moderate adverse events . This preliminary study showed that a larger study evaluating the clinical outcomes of MT for people with moderate COPD appears feasible Study design : R and omized clinical trial . Objective : To investigate the effect of including manual therapy ( MT ) in a pulmonary rehabilitation program for patients with chronic obstructive pulmonary disease ( COPD ) . Background : The primary source of exercise limitation in people with COPD is dyspnea . The dyspnea is partly caused by changes in chest wall mechanics , with an increase in chest wall rigidity ( CWR ) contributing to a decrease in lung function . As MT is known to increase joint mobility , administering MT to people with COPD carries with it the potential to influence CWR and lung function . Methods : Thirty-three participants with COPD , aged between 55 and 70 years ( mean = 65·5±4 years ) , were r and omly assigned to three groups : pulmonary rehabilitation ( PR ) only , soft tissue therapy ( ST ) and PR , and ST , spinal manipulative therapy ( SM ) , and PR . Outcome measures including forced expiratory volume in the 1st second ( FEV1 ) , forced vital capacity ( FVC ) , 6-minute walking test ( 6MWT ) , St. George 's respiratory question naire ( SGRQ ) , and the hospital anxiety and depression ( HAD ) scale were recorded at 0 , 8 , 16 , and 24 weeks . Results : There was a significant difference in FVC between the three groups at 24 weeks ( P = 0·04 ) . For the ST+SM+PR group versus PR only the increase was 0·40 l ( CI : 0·02 , 0·79 ; P = 0·03 ) . No major or moderate adverse events ( AE ) were reported following the administration of 131 ST and 272 SM interventions . Discussion : The increase in FVC is a unique finding . Although the underlying mechanisms responsible for this outcome are not yet understood , the most likely explanation is the synergistic effect result ing from the combination of interventions . These results support the call for a larger clinical trial in the use of MT for COPD OBJECTIVE To determine comorbidities that cause pain and the potential contributors to pain in individuals with chronic obstructive pulmonary disease ( COPD ) . DESIGN Prospect i ve cross-sectional survey study . SETTING Pulmonary rehabilitation programs of 6 centers . PARTICIPANTS A convenience sample of individuals with COPD ( N=137 ) who attended pulmonary rehabilitation programs . In total , 100 ( 73 % ) returned the survey packages . Of those responders , 96 participants ( 70 % ) were included in the analyses . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Pain was measured using the Brief Pain Inventory . The question naire used to obtain information about health conditions that might contribute to pain and a medication record asked , in lay terms , about comorbidities that cause pain . The health conditions that cause pain were then vali date d by health professionals . Demographics , fatigue , dyspnea , quality of life , and self-efficacy were also measured using question naires . RESULTS Pain was reported in 71 % ( 68/96 ) of participants . Low back pain was the most common location ( 41 % ) . Arthritis ( 75 % ) , back problems ( 47 % ) , and muscle cramps ( 46 % ) were the most common comorbidities that caused pain . Lower self-efficacy , and renting rather than home ownership increased the likelihood of pain ( P<.05 ) . Pain severity and Brief Fatigue Inventory scores contributed to pain interference scores ( P<.05 ) . CONCLUSIONS Pain was highly prevalent in pulmonary rehabilitation program participants with COPD . The most common causes of pain were musculoskeletal conditions . Pain severity and higher levels of fatigue contributed to how pain interfered with daily aspects of living . The assessment and management of pain need to be addressed within the overall care of individuals with COPD QUESTIONS In people with chronic obstructive pulmonary disease , does the Manual Diaphragm Release Technique improve diaphragmatic mobility after a single treatment , or cumulatively ? Does the technique also improve exercise capacity , maximal respiratory pressures , and kinematics of the chest wall and abdomen ? DESIGN R and omised , controlled trial with concealed allocation , intention-to-treat analysis , and blinding of participants and assessors . PARTICIP \n Output:\n " }, { "from": "agent", "value": "No effect on lung function was found , while results on exercise capacity were contrasting .\nFew RCTs of poor method ological quality are available on the effects of MT in COPD ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: BACKGROUND Effective internet-based programs for depression usually incorporate a component that provides telephone or email contact . Open access websites , without such contact , show high rates of attrition and poorer outcomes . The present study was design ed as an exploratory investigation of the parameters that influence the effectiveness and retention of users on open access websites . We investigated whether brief cognitive behaviour therapy ( CBT ) was as effective as an extended version , whether add-on components of behaviour therapy or stress management contributed to positive outcomes , and whether longer programs were associated with greater attrition . METHOD An online r and omized controlled trial ( RCT ) was conducted between 13 January 2005 and 26 May 2005 ( 19 weeks ) . A total of 2794 registrants ( 1846 women and 948 men ; median age category 35 - 44 years ) with elevated scores on the Goldberg Depression Scale of 5.96 ( S.D.=2.09 ) elected online to be r and omized to one of six versions of a CBT website . The versions were compiled consisting of various components of brief CBT , extended CBT , behaviour strategies , stress management and problem solving . RESULTS A total of 20.4 % of participants completed the assigned intervention . The interaction of measurement occasion and treatment version was significant [ F(13,131)=2.20 , p=0.01 ] . A single module of brief introductory CBT was not effective in reducing depression symptoms . However , extended CBT with or without the addition of behaviour strategies result ed in the reduction of depression . CONCLUSIONS Brief CBT-based interventions are not as effective as extended interventions . However , longer programs are associated with higher rates of dropout Current approaches to the treatment of panic disorder ( PD ) include a treatment package consisting of relaxation training ( RT ) , cognitive therapy ( CT ) , and exposure-based components . In an examination of the separate effects of RT and CT without formally taught exposure of any form , 64 PD patients were assigned r and omly to one of these treatment protocol s or to a minimal-contact control ( MCC ) condition . Both RT and CT were superior to the MCC condition on a variety of measures pertaining to panic , global psychological functioning , agoraphobic fear , and other associated fears . A significantly greater percentage of patients were classified as treatment responders ( based on a composite index ) after CT ( 82 % ) and RT ( 68 % ) , compared with the control group ( 36 % ) . On measures of agoraphobic fear , CT patients fared slightly better than RT patients . Some support was demonstrated for specific cognitive changes after CT , although treatment specificity was not strongly supported overall . These results are discussed in light of current theories of PD and the presumed importance of exposure in its treatment Mild depressive syndromes are highly prevalent among primary -care patients . Evidence -based treatment recommendations need to be derived directly from this diagnostically heterogeneous group . The primary aim was to assess the efficacy of sertraline and cognitive-behavioural group therapy for treatment of depressed primary -care patients , the secondary aim was to evaluate if receiving treatment according to free choice is associated with a better outcome than r and omization to a particular treatment . We conducted a r and omized , placebo-controlled , single-centre , 10-wk trial with five arms : sertraline ( flexible dosages up to 200 mg/d ) ( n = 83 ) ; placebo ( n = 83 ) ; manual-guided cognitive-behavioural group therapy ( one individual session and nine group sessions per 90 min ) ( n = 61 ) ; guided self-help group ( control condition , n = 59 ) ; and treatment with sertraline or cognitive-behavioural group therapy according to patients ' choice ( n = 82 ) . From 1099 consecutively screened adult patients , 368 formed the intent-to-treat population with milder forms of depression . Primary outcome was a global efficacy measure combining z-converted Hamilton Depression Rating Scale and clinician-rated Inventory for Depressive Symptomatology scores . Sertraline was superior to placebo ( p = 0.03 ) . Outcome for guided self-help groups was worse compared to cognitive-behavioural group therapy ( p = 0.002 ) and compared to all other treatment arms including pill placebo ( secondary analyses ) . Outcome in the patients ' choice arm was similar to that in the sertraline and cognitive-behavioural group therapy . Overall , sertraline is efficacious in primary -care patients with milder forms of depression . The superiority of cognitive-behavioural group therapy over guided self-help groups might partly be explained by ' nocebo ' effects of the latter BACKGROUND Although effective therapies for social phobia exist , many individuals refrain from seeking treatment owing to the embarrassment associated with help-seeking . Internet-based cognitive-behavioural self-help can be an alternative , but adherence is a problem . AIMS To evaluate a 9-week programme of internet-based therapy design ed to increase treatment adherence by the addition of short weekly telephone calls , nine in all , with a total duration of 95 min . METHOD In a r and omised controlled trial the effects of internet-based cognitive-behavioural therapy in the treatment group ( n=29 ) were compared with a waiting-list control group ( n=28 ) . RESULTS Compared with the control group the treated participants experienced greater reductions on measures of general and social anxiety , avoidance and depression . Adherence to treatment was high , with 93 % finishing the complete treatment package . One year later all improvements were maintained . CONCLUSIONS This study provides evidence to support the use of internet-based treatment supplemented by short , weekly telephone calls BACKGROUND Major depression can be treated by means of cognitive-behavioural therapy , but as skilled therapists are in short supply there is a need for self-help approaches . Many individuals with depression use the internet for discussion of symptoms and to share their experience . AIMS To investigate the effects of an internet-administered self-help programme including participation in a monitored , web-based discussion group , compared with participation in web-based discussion group only . METHOD A r and omised controlled trial was conducted to compare the effects of internet-based cognitive-behavioural therapy with minimal therapist contact ( plus participation in a discussion group ) with the effects of participation in a discussion group only . RESULTS Internet-based therapy with minimal therapist contact , combined with activity in a discussion group , result ed in greater reductions of depressive symptoms compared with activity in a discussion group only ( waiting-list control group ) . At 6 months ' follow-up , improvement was maintained to a large extent . CONCLUSIONS Internet-delivered cognitive cognitive-behavioural therapy should be pursued further as a complement or treatment alternative for mild-to-moderate depression Background Guided self-help programs for depression ( with associated therapist contact ) have been successfully delivered over the Internet . However , previous trials of pure self-help Internet programs for depression ( without therapist contact ) , including an earlier trial conducted by us , have failed to yield positive results . We hypothesized that methods to increase participant usage of the intervention , such as postcard or telephone reminders , might result in significant effects on depression . Objectives This paper presents a second r and omized trial of a pure self-help Internet site , ODIN ( Overcoming Depression on the InterNet ) , for adults with self-reported depression . We hypothesized that frequently reminded participants receiving the Internet program would report greater reduction in depression symptoms and greater improvements in mental and physical health functioning than a comparison group with usual treatment and no access to ODIN . Methods This was a three-arm r and omized control trial with a usual treatment control group and two ODIN intervention groups receiving reminders through postcards or brief telephone calls . The setting was a nonprofit health maintenance organization ( HMO ) . We mailed recruitment brochures by US post to two groups : adults ( n = 6030 ) who received depression medication or psychotherapy in the previous 30 days , and an age- and gender-matched group of adults ( n = 6021 ) who did not receive such services . At enrollment and at 5- , 10- and 16-weeks follow-up , participants were reminded by email ( and telephone , if nonresponsive ) to complete online versions of the Center for Epidemiological Studies Depression Scale ( CES-D ) and the Short Form 12 ( SF-12 ) . We also recorded participant HMO health care services utilization in the 12 months following study enrollment . Results Out of a recruitment pool of 12051 approached subjects , 255 persons accessed the Internet enrollment site , completed the online consent form , and were r and omized to one of the three groups : ( 1 ) treatment as usual control group without access to the ODIN website ( n = 100 ) , ( 2 ) ODIN program group with postcard reminders ( n = 75 ) , and ( 3 ) ODIN program group with telephone reminders ( n = 80 ) . Across all groups , follow-up completion rates were 64 % ( n = 164 ) at 5 weeks , 68 % ( n = 173 ) at 10 weeks , and 66 % ( n = 169 ) at 16 weeks . In an intention-to-treat analysis , intervention participants reported greater reductions in depression compared to the control group ( P = .03 ; effect size = 0.277 st and ard deviation units ) . A more pronounced effect was detected among participants who were more severely depressed at baseline ( P = .02 ; effect size = 0.537 st and ard deviation units ) . By the end of the study , 20 % more intervention participants moved from the disordered to normal range on the CES-D. We found no difference between the two intervention groups with different reminders in outcomes measures or in frequency of log-ons . We also found no significant intervention effects on the SF-12 or health care services . Conclusions In contrast to our earlier trial , in which participants were not reminded to use ODIN , in this trial we found a positive effect of the ODIN intervention compared to the control group . Future studies should address limitations of this trial , including relatively low enrollment and follow-up completion rates , and a restricted number of outcome measures . However , the low incremental costs of delivering this Internet program makes it feasible to offer this type of program to large population s with widespread Internet access Background Self-help therapies are often effective in reducing mental health problems . We developed a new Web-based self-help intervention based on problem-solving therapy , which may be used for people with different types of comorbid problems : depression , anxiety , and work-related stress . Objective The aim was to study whether a Web-based self-help intervention is effective in reducing depression , anxiety , and work-related stress ( burnout ) . Methods A total of 213 participants were recruited through mass media and r and omized to the intervention ( n = 107 ) or a waiting list control group ( n = 106 ) . The Web-based course took 4 weeks . Every week an automated email was sent to the participants to explain the contents and exercises for the coming week . In addition , participants were supported by trained psychology students who offered feedback by email on the completed exercises . The core element of the intervention is a procedure in which the participants learn to approach solvable problems in a structured way . At pre-test and post-test , we measured the following primary outcomes : depression ( CES-D and MDI ) , anxiety ( SCL-A and HADS ) , and work-related stress ( MBI ) . Quality of life ( EQ-5D ) was measured as a secondary outcome . Intention-to-treat analyses were performed . Results Of the 213 participants , 177 ( 83.1 % ) completed the baseline and follow-up question naires ; missing data were statistically imputed . Of all 107 participants in the intervention group , 9 % ( n = 10 ) dropped out before the course started and 55 % ( n = 59 ) completed the whole course . Among all participants , the intervention was effective in reducing symptoms of depression ( CES-D : Cohen ’s d = 0.50 , 95 % confidence interval ( CI ) 0.22 - 0.79 ; MDI : d = 0.33 , 95 % CI 0.03 - 0.63 ) and anxiety ( SCL-A : d = 0.42 , 95 % CI 0.14 - 0.70 ; HADS : d = 0.33 , 95 % CI 0.04 - 0.61 ) as well as in enhancing quality of life ( d = 0.31 , 95 % CI 0.03 - 0.60 ) . Moreover , a higher percentage of patients in the intervention group experienced a significant improvement in symptoms ( CES-D : odds ratio [ OR ] = 3.5 , 95 % CI 1.9 - 6.7 ; MDI : OR = 3.7 , 95 % CI 1.4 - 10.0 ; SCL-A : OR = 2.1 , 95 % CI 1.0 - 4.6 ; HADS : OR = 3.1 , 95 % CI 1.6 - 6.0 ) . Patients in the intervention group also recovered more often ( MDI : OR = 2.2 ; SCL-A : OR = 2.0 ; HADS < 8) , although these results were not statistically significant . The course was less effective for work-related stress , but participants in the intervention group recovered more often from burnout than those in the control group ( OR = 4.0 , 95 % CI 1.2 - 13.5 ) . Conclusions We demonstrated statistically and clinical ly significant effects on symptoms of depression and anxiety . These effects were even more pronounced among participants with more severe baseline problems and for participants who fully completed the course . The effects on work-related stress and quality of life were less clear . To our knowledge , this is the first trial of a Web-based , problem-solving intervention \n Output:\n " }, { "from": "agent", "value": "BACKGROUND Cognitive-behavioural therapy (CBT)-based guided self-help ( GSH ) has been suggested to be an effective intervention for mild to moderate anxiety and depression , yet the evidence seems inconclusive , with some studies reporting that GSH is effective and others finding that GSH is ineffective .\nMeta- analysis indicated the effectiveness of GSH at post-treatment , although GSH was found to have limited effectiveness at follow-up or among more clinical ly representative sample s. Studies that reported greater effectiveness of GSH tended to be of lower method ological quality and generally involved participants who were self-selected rather than recruited through clinical referrals .\nFurther rigorous evidence based on clinical population s that examines longer-term outcomes is required before CBT-based GSH interventions can be deemed effective for adults accessing primary care services for treatment of anxiety and depression" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results Background : The purpose of this study was threefold : ( 1 ) to determine the scientific quality of published r and omized trials in the American Volume of The Journal of Bone and Joint Surgery from 1988 through 2000 , ( 2 ) to identify predictors of study quality , and ( 3 ) to evaluate inter-rater agreement in the scoring of study quality with use of a simple scale . Methods : H and search es of The Journal of Bone and Joint Surgery were conducted in duplicate to identify r and omized clinical trials . Of 2468 studies identified , seventy-two ( 2.9 % ) met all eligibility criteria . Two investigators each assessed the quality of the study under blinded conditions and abstract ed relevant data . Results : The mean score ( and st and ard error ) for the quality of the seventy-two r and omized trials was 68.1 % ± 1.6 % ; 60 % ( forty-three ) scored < 75 % . Drug trials had a significantly higher mean quality score than did surgical trials ( 72.8 % compared with 63.9 % , p < 0.05 ) . Regression analysis revealed that cited affiliation with an epidemiology department and cited funding were associated with higher quality scores . Failure to conceal r and omization , to blind outcome assessors , and to describe why patients were excluded result ed in significantly lower quality scores ( p < 0.05 ) , more than the 5 % decrease expected by removal of each item . A priori calculations of sample size were rarely performed in the review ed studies , and only 2 % of the studies with negative results included a post hoc power analysis . The Detsky quality scale met accepted st and ards of interobserver reliability ( kappa , 0.87 ; 95 % confidence interval , 0.70 to 0.95 ) . Conclusions : Few studies published in The Journal of Bone and Joint Surgery were r and omized trials . More than half of the trials were limited by a lack of concealed r and omization , lack of blinding of outcome assessors , or failure to report reasons for excluding patients . Application of st and ardized guidelines for the reporting of clinical trials in orthopaedics should improve quality Background The choice of different graft types and surgical techniques used when reconstructing a torn anterior cruciate ligament may influence the long-term prevalence of osteoarthritis and functional outcomes . Hypothesis There are no differences in the prevalence of knee osteoarthritis or knee function in patients undergoing reconstruction of a torn anterior cruciate ligament with 4-str and hamstring autograft versus patellar tendon — bone autograft . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods Seventy-two patients with subacute or chronic rupture of the anterior cruciate ligament were r and omly assigned to autograft reconstruction with 4-str and gracilis and semitendinosus tendon ( HAM ) ( N = 37 ) or with patellar tendon — bone ( PTB ) ( N = 35 ) from the ipsilateral side . Outcome measurements were the Cincinnati knee score , single-legged hop tests , isokinetic muscle strength tests , pain , knee joint laxity test ( KT-1000 arthrometer ) , and a radiologic evaluation ( Kellgren and Lawrence ) at 10-year follow-up . Results At 10 years , 57 patients ( 79 % ) were eligible for evaluation—29 in the HAM group and 28 in the PTB group . No differences were found between the 2 graft groups with respect to the Cincinnati knee score , the single-legged hop tests , pain , muscle strength measurements , or knee joint laxity . Fifty-five percent and 64 % of the patients had osteoarthritis corresponding to Kellgren and Lawrence grade 2 or more in the HAM and the PTB groups , respectively ( P = .27 ) . For the uninvolved knee , the corresponding numbers were 28 % and 22 % ( P = .62 ) . Conclusion At 10 years postoperatively , no statistically significant differences in clinical outcome between the 2 graft types were found . The prevalence of osteoarthritis was significantly higher in the operated leg than in the contralateral leg , but there were no significant differences between the 2 groups . The results indicate that the choice of graft type after an anterior cruciate ligament injury has minimal influence on the prevalence of osteoarthritis 10 years after surgery Seventy-two patients with subacute or chronic rupture of the anterior cruciate ligament were r and omly assigned to autograft reconstruction with four-str and gracilis and semitendinosus tendon ( N = 37 ) or with patellar tendon-bone ( N = 35 ) from the ipsilateral side . The groups were similar in terms of age , sex , level of activity , degree of laxity , meniscal lesions found surgically , and rehabilitation program . The follow-up was performed at another hospital by independent observers after 6 , 12 , and 24 months . Sixty-one patients ( 32 with hamstring tendon grafts and 29 with patellar tendon grafts ) complied with the follow-up routine for the full 24 months . No differences were found between the groups with respect to Cincinnati functional score , KT-1000 arthrometer measurements , or stairs hopple test results . The subjective result and the single-legged hop test result were better for the hamstring tendon group after 6 and 12 months , but no differences were found after 24 months . The hamstring tendon group showed better isokinetic knee extension strength than did the patellar tendon group after 6 months , but not after 12 and 24 months . There was a significant weakness in isokinetic knee flexion strength among the hamstring tendon group . Anterior knee pain was not significantly different between the groups , but kneeling pain was significantly less common in the hamstring tendon group after 24 months We studied 79 patients with unilateral injury to the anterior cruciate ligament ( ACL ) . The patients were r and omly allocated to reconstruction with autologous patellar bone-tendon-bone ( BTB ) grafts ( 49 knees ) or hamstring tendon ( ST ) grafts ( 30 knees ) . We measured anterior tibial translation ( ATT ) during isokinetic concentric contraction exercise 18–20 months after surgery using a computerized electrogoniometer . In both groups the highest ATT during exercise was observed at a knee flexion of about 20 ° and was 13.5±3.0 mm in the BTB group and 13.9±3.4 mm in the ST group . There was no difference in the ATT between the reconstructed and healthy knees . For a range of knee flexion between 30 and 50 ° the ATT in the ST group was significantly higher on the reconstructed side than on the healthy side . In the BTB group , the mean ATT in the reconstructed group was similar to that on the healthy side at a knee flexion angle between 0 and 90 ° .RésuméNous avons étudié 79 malades avec une rupture unilatérale du ligament croiseur antérieur ( ACL ) . Les malades étaient r and omisés pour avoir une reconstruction avec greffe autologue os-tendon-os rotulien ( BTB ; 49 genoux ) ou une greffe des tendons ischiojambiers ( ST ; 30 genoux ) . Nous avons mesuré la translation tibiale antérieure ( ATT ) pendant la contraction concentrique isocinétique , 18–20 mois après la chirurgie en utilisant un électrogoniomètre informatisé . Dans les deux groupes le plus haut ATT pendant l'exercice a été observé à une flexion du genou d'approximativement 20 ° et était de 13,5±3,0 mm dans le groupe BTB et 13,9±3,4 mm dans le groupe ST . Il n'y avait aucune différence dans la translation entre les genoux reconstruit et les genoux sains . Pour une flexion du genou entre 30 et 50 ° , l'ATT dans le groupe ST était significativement plus haut du côté reconstruit que du côté sain . Dans le groupe BTB , l'ATT dans le groupe reconstruit était semblable à celui sur le côté sain à un angle de la flexion du genou entre 0 et 90 ° The aims of the study were to analyse the change in knee laxity over time after anterior cruciate ligament ( ACL ) reconstruction , using either bone – patellar – tendon – bone ( BPTB ) or hamstring ( HS ) tendon autografts , and to compare the knee laxity measurements between the study groups both pre-operatively and on multiple follow-up occasions . Another aim was to compare the radiographic findings in terms of degenerative changes between the study groups . A r and omised series of 71 patients , who underwent ACL reconstruction using BPTB or HS tendon autografts and interference screw fixation , were included in the study . Of these patients , 47/71 ( 66 % ) attended a clinical examination , including laxity measurements using the KT-1000 arthrometer , pre-operatively and on four post-operative occasions ; 6 months , 1 year , 2 years and 7 years after the reconstruction . The BPTB group consisted of 22 patients , while there were 25 patients in the HS group . There were no significant differences in the mean side-to-side knee laxity between the BPTB and the HS group pre-operatively or at the follow-up examinations . There was a tendency towards a reduction in side-to-side knee laxity over time in both groups , measured with the KT-1000 arthrometer . The decrease was significant when analysing the injured and uninjured knee separately ( injured side p < 0.001 ( BPTB ) and p = 0.005 ( HS ) , uninjured side p = 0.008 and p = 0.042 , respectively ) . Forty-four patients ( BPTB 21 , ST 23 ) underwent a radiographic assessment at the 7-year follow-up , which revealed no significant differences between the study groups in terms of osteoarthritic findings classified according to the Fairbank and Ahlbäck rating systems . In overall terms , osteoarthritis was identified in 16 % ( BPTB 19 % ; ST 13 % ; n.s . ) according to the Ahlbäck rating system and 68 % ( BPTB 67 % ; ST 70 % ; n.s . ) according to the Fairbank rating system . There were no significant differences in knee laxity measurements between the two study groups pre-operatively or at 7 years . A decrease in knee laxity over time was seen in both groups . There were no significant differences between the BPTB and ST groups in terms of osteoarthritic findings at 7 years A five-year , prospect i ve , r and omized follow-up study was done to compare three methods for repair of a rupture of the anterior cruciate ligament of the knee : acute primary repair ( Group 1 ) , acute repair with a synthetic ligament-augmentation device ( Group 2 ) , and acute repair augmented with an autologous bone-patellar ligament-bone graft ( Group 3 ) . One hundred and fifty patients who had an acute rupture of the anterior cruciate ligament were r and omized to one of the three repair groups , with fifty patients in each group . The patients were between sixteen and fifty years old ( mean , twenty-nine years old ) . All patients had the operation within ten days after the injury . The rehabilitation protocol was identical for each group . The patients were evaluated prospect ively at one , two , and five years with use of the Tegner scoring system for level of activity and the scoring system of Lysholm and Gillquist for function , and the stability of the knee was assessed with clinical examination and with use of the KT-1000 arthrometer . One hundred and thirty-one patients completed the study and ten other patients were known to have had a failure of the procedure , a 94 per cent rate of follow-up . All three groups had a lower level of activity at the five-year follow-up evaluation than they had had before the injury . The patients who had had augmentation with a patellar-ligament graft had a significantly higher mean level of activity at two years than those who had had non-augmented repair ( p = 0.002 ) and those who had had repair with a synthetic ligament-augmentation device ( p = 0.01 ) . They also had a significantly higher mean \n Output:\n " }, { "from": "agent", "value": "Many trials were at high risk of bias reflecting inadequate methods of r and omization , lack of blinding and incomplete assessment of outcome .Pooled data for primary outcomes , reported in a minority of trials , showed no statistically significant differences between the two graft choices for functional assessment ( single leg hop test ) , return to activity , Tegner and Lysholm scores , and subjective measures of outcome .\nThere were also no differences found between the two interventions for re-rupture or International Knee Documentation Committee scores .\nAll tests ( instrumental , Lachman , pivot shift ) for static stability consistently showed that PT reconstruction result ed in a more statically stable knee compared with HT reconstruction .\nConversely , patients experienced more anterior knee problems , especially with kneeling , after PT reconstruction .\nPT reconstructions result ed in a statistically significant loss of extension range of motion and a trend towards loss of knee extension strength .\nHT reconstructions demonstrated a trend towards loss of flexion range of motion and a statistically significant loss of knee flexion strength .\nThere is insufficient evidence to draw conclusions on differences between the two grafts for long-term functional outcome .\nWhile PT reconstructions are more likely to result in statically stable knees , they are also associated with more anterior knee problems" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: CONTEXT In previous smaller trials , a procalcitonin ( PCT ) algorithm reduced antibiotic use in patients with lower respiratory tract infections ( LRTIs ) . OBJECTIVE To examine whether a PCT algorithm can reduce antibiotic exposure without increasing the risk for serious adverse outcomes . DESIGN , SETTING , AND PATIENTS A multicenter , noninferiority , r and omized controlled trial in emergency departments of 6 tertiary care hospitals in Switzerl and with an open intervention of 1359 patients with mostly severe LRTIs r and omized between October 2006 and March 2008 . INTERVENTION Patients were r and omized to administration of antibiotics based on a PCT algorithm with predefined cutoff ranges for initiating or stopping antibiotics ( PCT group ) or according to st and ard guidelines ( control group ) . Serum PCT was measured locally in each hospital and instructions were Web-based . MAIN OUTCOME MEASURES Noninferiority of the composite adverse outcomes of death , intensive care unit admission , disease-specific complications , or recurrent infection requiring antibiotic treatment within 30 days , with a predefined noninferiority boundary of 7.5 % ; and antibiotic exposure and adverse effects from antibiotics . RESULTS The rate of overall adverse outcomes was similar in the PCT and control groups ( 15.4 % [ n = 103 ] vs 18.9 % [ n = 130 ] ; difference , -3.5 % ; 95 % CI , -7.6 % to 0.4 % ) . The mean duration of antibiotics exposure in the PCT vs control groups was lower in all patients ( 5.7 vs 8.7 days ; relative change , -34.8 % ; 95 % CI , -40.3 % to -28.7 % ) and in the subgroups of patients with community-acquired pneumonia ( n = 925 , 7.2 vs 10.7 days ; -32.4 % ; 95 % CI , -37.6 % to -26.9 % ) , exacerbation of chronic obstructive pulmonary disease ( n = 228 , 2.5 vs 5.1 days ; -50.4 % ; 95 % CI , -64.0 % to -34.0 % ) , and acute bronchitis ( n = 151 , 1.0 vs 2.8 days ; -65.0 % ; 95 % CI , -84.7 % to -37.5 % ) . Antibiotic-associated adverse effects were less frequent in the PCT group ( 19.8 % [ n = 133 ] vs 28.1 % [ n = 193 ] ; difference , -8.2 % ; 95 % CI , -12.7 % to -3.7 % ) . CONCLUSION In patients with LRTIs , a strategy of PCT guidance compared with st and ard guidelines result ed in similar rates of adverse outcomes , as well as lower rates of antibiotic exposure and antibiotic-associated adverse effects . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N95122877 Background : Biological markers as an expression of systemic inflammation have been recognised as useful for evaluating the host response in community-acquired pneumonia ( CAP ) . The objective of this study was to evaluate whether the biological markers procalcitonin ( PCT ) and C-reactive protein ( CRP ) might reflect stability after 72 h of treatment and the absence of subsequent severe complications . Methods : A prospect i ve cohort study was performed in 394 hospitalised patients with CAP . Clinical stability was evaluated using modified Halm ’s criteria : temperature ⩽37.2 ° C ; heart rate ⩽100 beats/min ; respiratory rate ⩽24 breaths/min ; systolic blood pressure ⩾90 mm Hg ; oxygen saturation ⩾90 % ; or arterial oxygen tension ⩾60 mm Hg . PCT and CRP levels were measured on day 1 and after 72 h. Severe complications were defined as mechanical ventilation , shock and /or intensive care unit ( ICU ) admission , or death after 72 h of treatment . Results : 220 patients achieved clinical stability at 72 h and had significantly lower levels of CRP ( 4.2 vs 7 mg/dl ) and of PCT ( 0.33 vs 0.48 ng/ml ) . Regression logistic analyses were performed to calculate several areas under the ROC curve ( AUC ) to predict severe complications . The AUC for clinical stability was 0.77 , 0.84 when CRP was added ( p = 0.059 ) and 0.77 when PCT was added ( p = 0.45 ) . When clinical stability was achieved within 72 h and marker levels were below the cut-off points ( 0.25 ng/ml for PCT and 3 mg/dl for CRP ) , no severe complications occurred . Conclusions : Low levels of CRP and PCT at 72 h in addition to clinical criteria might improve the prediction of absence of severe complications Background : The induction of C-reactive Protein ( CRP ) may be attenuated by corticosteroids , whereas Procalcitonin ( PCT ) appears to be unaltered . We investigated , whether in community-acquired pneumonia ( CAP ) a combined antibiotic-corticosteroid therapy may actually lead to different slopes of decline of these inflammatory markers . Patients and Methods : We studied the slopes of decline of PCT and CRP serum levels during 7 consecutive days as well as clinical parameters in a group of patients with CAP on or off corticosteroids . Patients with underlying COPD received systemic corticosteroids ( n = 10 ) , while non- COPD patients ( n = 10 ) presenting with CAP alone formed the control group . All patients were treated with antibiotics . Results : At baseline , relevant clinical and laboratory characteristics of the two groups were similar . Regarding the decreasing shapes of the curves from PCT and CRP , no significant differences were found ( p-value = 0.48 for the groups for CRP , respectively 0.64 for PCT ) . All patients showed an uneventful recovery . Conclusion : In patients with COPD and CAP , the time courses over 7 days of PCT and CRP showed a nearly parallel decline compared to non- COPD patients with CAP . Contrary to the induction phase , corticosteroids do not modify the time-dependent decay of PCT and CRP when the underlying infectious disease ( CAP ) is adequately treated Objectives Procalcitonin ( PCT ) kinetics is a good prognosis marker in infectious diseases , but few studies of community-acquired pneumonia ( CAP ) have been performed in intensive care units ( ICU ) . We analyzed the relationship between PCT kinetics and outcome in ICU patients with severe CAP . Design and setting Prospect i ve observational study in a 16-bed university hospital ICU . Patients 100 critically ill patients with community-acquired pneumonia . Measurements and results Median PCT was 5.2 ng/ml on day 1 and 2.9 ng/ml on day 3 . It increased from day 1 to day 3 in nonsurvivors but decreased in survivors . In multivariate analysis four variables were associated with death : invasive ventilation ( odds ratio 10− ) , multilobar involvement ( 5.6− ) , LOD score ( 6.9− ) , and PCT increase from day 1 to day 3 ( 4.5− ) . In intubated patients with a PCT level below 0.95 ng/ml on day 3 the survival rate was 95 % . Conclusion Increased PCT from day 1 to day 3 in severe CAP is a poor prognosis factor . A PCT level less than 0.95 ng/ml on day 3 in intubated patients is associated with a favorable outcome RATIONALE In patients with community-acquired pneumonia , guidelines recommend antibiotic treatment for 7 to 21 d. Procalcitonin is elevated in bacterial infections , and its dynamics have prognostic implication s. OBJECTIVE To assess procalcitonin guidance for the initiation and duration of antibiotic therapy in community-acquired pneumonia . METHODS In a r and omized intervention trial , 302 consecutive patients with suspected community-acquired pneumonia were included . Data were assessed at baseline , after 4 , 6 , and 8 d , and after 6 wk . The control group ( n = 151 ) received antibiotics according to usual practice . In the procalcitonin group ( n = 151 ) , antibiotic treatment was based on serum procalcitonin concentrations as follows : strongly discouraged , less than 0.1 microg/L ; discouraged , less than 0.25 microg/L ; encouraged , greater than 0.25 microg/L ; strongly encouraged , greater than 0.5 microg/L. The primary endpoint was antibiotic use ; secondary endpoints were measures of clinical , laboratory , and radiographic outcome . RESULTS At baseline , both groups were similar regarding clinical , laboratory , and microbiology characteristics , and Pneumonia Severity Index . Procalcitonin guidance reduced total antibiotic exposure ( relative risk , 0.52 ; 95 % confidence interval , 0.48 - 0.55 ; p < 0.001 ) , antibiotic prescriptions on admission ( 85 vs. 99 % ; p < 0.001 ) , and antibiotic treatment duration ( median , 5 vs. 12 d ; p < 0.001 ) compared with patients treated according to guidelines . After adjustment for Pneumonia Severity Index , the hazard ratio of antibiotic discontinuation was higher in the procalcitonin group than in the control group ( 3.2 ; 95 % confidence interval , 2.5 to 4.2 ) . Outcome was similar in both groups , with an overall success rate of 83 % . CONCLUSIONS Procalcitonin guidance substantially reduces antibiotic use in community-acquired pneumonia . These findings may have important clinical and public health implication BACKGROUND Acute respiratory tract infections are the most common reason for antibiotic therapy in primary care despite their mainly viral etiology . A laboratory test measuring procalcitonin levels in blood specimens was suggested as a tool to reduce unnecessary prescribing of antibiotics . We consider whether antibiotic therapy guided by procalcitonin reduces the use of antibiotics without increasing the restrictions experienced by patients by more than 1 day . METHODS Fifty-three primary care physicians recruited 458 patients , each patient with an acute respiratory tract infection and , in the physician 's opinion , in need of antibiotics . Patients were central ly r and omized to either a procalcitonin-guided approach to antibiotic therapy or to a st and ard approach . For patients r and omized to procalcitonin-guided therapy , the use of antibiotics was more or less strongly discouraged ( procalcitonin level , < or = 0.1 or < or = 0.25 microg/L , respectively ) or recommended ( procalcitonin level , > 0.25 microg/L ) . Follow-up data were collected at 7 days by treating physicians and at 14 and 28 days by blinded interviewers . RESULTS Adjusted for baseline characteristics , the mean increase at 14 days in days in which activities were restricted was 0.14 with procalcitonin-guided therapy ( 95 % confidence interval [ CI ] , -0.53 to 0.81 days ) , which met our criterion of an increase in days in which activities were restricted by no more than 1 day . With procalcitonin-guided therapy , the antibiotic prescription rate was 72 % lower ( 95 % CI , 66%-78 % ) than with st and ard therapy . Both approaches led to a similar proportion of patients reporting symptoms of ongoing or relapsing infection at 28 days ( adjusted odds ratio , 1.0 [ 95 % CI , 0.7 - 1.5 ] ) . CONCLUSIONS As an adjunct to guidelines , procalcitonin-guided therapy markedly reduces antibiotic use for acute respiratory tract infections in primary care without compromising patient outcome . In practice , this could be achieved with 1 to 2 procalcitonin measurements in patients for whom the physician intends to prescribe antibiotics STUDY OBJECTIVES To evaluate the usefulness of procalcitonin serum levels as a predictor of etiology and prognosis in adult patients with community-acquired pneumonia ( CAP ) when they are stratified according to severity . DESIGN One-year , population -based , prospect i ve study . SETTING University teaching hospital . PATIENTS All adult patients who received a diagnosis of CAP throughout the study period . INTERVENTIONS AND MEASUREMENTS An extensive noninvasive microbiological workup was performed . In patients who gave informed consent , a blood sample was collected at the time the diagnosis of CAP was established to measure biological markers . Procalcitonin levels were measured by a commercially available monoclonal immunoluminometric assay ( limit of detection , 0.1 microg/L ) . Patients were classified according to microbial diagnosis , Patients Outcome Research Team pneumonia severity index ( PSI ) , and outcome measures , and procalcitonin levels were compared among groups . RESULTS Of 240 patients who received a diagnosis of CAP during the study period , procalcitonin concentrations were measured in 185 patients ( 77.1 % ) . Levels were higher in patients with high \n Output:\n " }, { "from": "agent", "value": "RESULTS The most thoroughly studied topic is the prediction of complications and death during hospital stay .\nPCT has predictive properties comparable to those of the Pneumonia Severity Index and the CURB65 scoring systems , and it may represent an addition to these indices .\nFurthermore , PCT levels may indicate aetiology as patients with typical bacterial infection have higher PCT levels than patients with atypical and viral aetiologies .\nThe literature also indicates that PCT can distinguish CAP from asthma and acute exacerbation of chronic obstructive pulmonary disease .\nSeveral studies and a meta- analysis have shown that administration of antibiotics according to a PCT algorithm in a hospital setting reduced the use of antibiotics with no evidence of an increased risk ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: PURPOSE The impact of body mass index ( BMI ) on survival after colorectal cancer diagnosis is poorly understood . This study assessed the association of pre- and postdiagnosis BMI with all-cause and cause-specific survival among men and women diagnosed with colorectal cancer in a prospect i ve cohort . PATIENTS AND METHODS Participants in the Cancer Prevention Study -II Nutrition Cohort reported weight and other risk factor information via a self-administered question naire at baseline in 1992 to 1993 . Up date d information on current weight and incident cancer was reported via periodic follow-up question naires . This analysis includes 2,303 cohort participants who were diagnosed with nonmetastatic colorectal cancer between baseline and mid 2007 and were observed for mortality from diagnosis through December 2008 . RESULTS A total of 851 participants with colorectal cancer died during the 16-year follow-up period , including 380 as a result of colorectal cancer and 153 as a result of cardiovascular disease ( CVD ) . In analyses of prediagnosis BMI ( weight reported at baseline in 1992 to 1993 ; mean , 7 years before colorectal cancer diagnosis ) , obese BMI ( ≥ 30 kg/m(2 ) ) relative to normal BMI ( 18.5 to 24.9 kg/m(2 ) ) was associated with higher risk of mortality result ing from all causes ( relative risk [ RR ] , 1.30 ; 95 % CI , 1.06 to 1.58 ) , colorectal cancer ( RR , 1.35 ; 95 % CI , 1.01 to 1.80 ) , and CVD ( RR , 1.68 ; 95 % CI , 1.07 to 2.65 ) . Postdiagnosis BMI ( based on weight reported ; mean , 1.5 years after diagnosis ) was not associated with all-cause or cause-specific mortality . CONCLUSION This study suggests that prediagnosis BMI , but not postdiagnosis BMI , is an important predictor of survival among patients with nonmetastatic colorectal cancer Obesity is a well-established risk factor for colorectal cancer ( CRC ) , and accumulating evidence suggests a differential influence of sex and anthropometric factors on the molecular carcinogenesis of the disease . The aim of the present study was to investigate the relationship between height , weight , bodyfat percentage , waist- and hip circumference , waist-hip ratio ( WHR ) , body mass index ( BMI ) and CRC risk according to KRAS and BRAF mutation status of the tumours , with particular reference to potential sex differences . KRAS and BRAF mutations were analysed by pyrosequencing in tumours from 494 incident CRC cases in the Malmö Diet and Cancer Study . Hazard ratios of CRC risk according to anthropometric factors and mutation status were calculated using multivariate Cox regression models . While all anthropometric measures except height were associated with an increased risk of KRAS-mutated tumours , only BMI was associated with an increased risk of KRAS wild type tumours overall . High weight , hip , waist , WHR and BMI were associated with an increased risk of BRAF wild type tumours , but none of the anthropometric factors were associated with risk of BRAF-mutated CRC , neither in the overall nor in the sex-stratified analysis . In men , several anthropometric measures were associated with both KRAS-mutated and KRAS wild type tumours . In women , only a high WHR was significantly associated with an increased risk of KRAS-mutated CRC . A significant interaction was found between sex and BMI with respect to risk of KRAS-mutated tumours . In men , all anthropometric factors except height were associated with an increased risk of BRAF wild type tumours , whereas in women , only bodyfat percentage was associated with an increased risk of BRAF wild type tumours . The results from this prospect i ve cohort study further support an influence of sex and lifestyle factors on different pathways of colorectal carcinogenesis , defined by KRAS and BRAF mutation status of the tumours Background : We hypothesized that precancer anthropometric variables are associated with mortality among women who developed colon cancer in a prospect i ve cohort , the Iowa Women 's Health Study ( IWHS ) . Methods : From 1986 to 2005 , 1,096 incident cases of colon cancer were identified ( mean age at diagnosis , 73 years ) . Anthropometric characteristics were self-measured before colon cancer diagnosis ( in 1986 ) . Cox proportional hazards regression was used to estimate hazard ratios ( HR ) and 95 % confidence intervals ( 95 % CI ) for all-cause and colon-cancer mortality , adjusted for age at cancer diagnosis , stage , education , smoking status , and pack-years of smoking . Results : During the follow-up of up to 20 years , 493 women died ; 289 had colon cancer as the underlying cause . The HRs of all-cause death were increased for the highest versus lowest tertile for weight ( HR , 1.39 ; 95 % CI , 1.10 - 1.76 ; P trend = 0.005 ) ; waist to hip ratio ( WHR ; HR , 1.36 ; 95 % CI , 1.08 - 1.72 ; P trend = 0.008 ) , and waist ( HR , 1.45 ; 95 % CI , 1.15 - 1.82 ; P trend = 0.001 ) . Compared with that for body mass index ( BMI ) of 18.5 to 24.9 kg/m2 , HRs were increased for BMI ≥30 kg/m2 ( HR , 1.45 ; 95 % CI , 1.14 - 1.85 ) and for the few women with BMI < 18.5 kg/m2 ( HR , 1.89 ; 95 % CI , 1.01 - 3.53 ) . Colon cancer mortality was positively associated with WHR and waist : HR , 1.37 ( 95 % CI , 1.02;1.85 ; P trend = 0.04 ) and 1.34 ( 95 % CI , 1.01 - 1.80 ; P trend = 0.05 ) , respectively , for the highest versus lowest tertile . Conclusion : Greater precancer anthropometric measures and BMI < 18.5 kg/m2 predicted poorer survival among colon cancer patients . Higher abdominal adiposity measured by WHR and waist was associated with increased risk of colon cancer death . Impact : Prediagnostic obesity may be a modifiable risk factor for death in colon cancer patients . Cancer Epidemiol Biomarkers Prev ; 19(9 ) ; 2229–37 . © 2010 AACR Background It remains unclear whether the increased risk of colorectal cancer ( CRC ) associated with obesity differs by gender , distribution of fat , tumour location and clinical ( TNM ) stage . The primary aim of this study was to examine these associations in 584 incident colorectal cancer cases from a Swedish prospect i ve population -based cohort including 28098 men and women . Methods Seven anthropometric factors ; height , weight , bodyfat percentage , hip circumference , waist circumference , BMI and waist-hip ratio ( WHR ) were categorized into quartiles of baseline anthropometric measurements . Relative risks of CRC , total risk as well as risk of different TNM stages , and risk of tumours located to the colon or rectum , were calculated for all cases , women and men , respectively , using multivariate Cox regression models . Results Obesity , as defined by all anthropometric variables , was significantly associated with an overall increased risk of CRC in both women and men . While none of the anthropometric measures was significantly associated with risk of tumour (T)-stage 1 and 2 tumours , all anthropometric variables were significantly associated with an increased risk of T-stage 3 and 4 , in particular in men . In men , increasing quartiles of weight , hip , waist , BMI and WHR were significantly associated with an increased risk of lymph node positive ( N1 and N2 ) disease , and risk of both non-metastatic ( M0 ) and metastatic ( M1 ) disease . In women , there were no or weak associations between obesity and risk of node-positive disease , but statistically significant associations between increased weight , bodyfat percentage , hip , BMI and M0 disease . Interestingly , there was an increased risk of colon but not rectal cancer in men , and rectal but not colon cancer in women , by increased measures of weight , hip- , waist circumference and bodyfat percentage . Conclusions This study is the first to show a relationship between obesity , measured as several different anthropometric factors , and an increased risk of colorectal cancer of more advanced clinical stage , in particular in men . These findings suggest that risk of CRC differs according to the method of characterising obesity , and also according to gender , location , and tumour stage There are few reports on factors that determine survival in advanced gastrointestinal cancer with weight loss . In these patients ( n = 91 , median weight loss 16.6 % ) , we prospect ively examined the importance of metastatic spread , anthropometry , blood parameters , Karnofsky performance status , appetite , and the acute-phase response as predictors of survival . Survival was calculated from date of assessment to the most recent clinic attendance ( ≥30 mo ) or until death . On multivariate analysis , metastatic spread ( p < 0.05 ) , Karnofsky performance status ( p < 0.01 ) , and C-reactive protein concentration ( p < 0.001 ) had independent prognostic value . In locally advanced disease ( n = 64 ) , Karnofsky performance status and C-reactive protein concentration remained significant . There was a significantly lower survival in patients with an acute-phase response ( median 136 days ) than in patients with no response ( median 466 days ; p < 0.01 ) . Performance status and the acute-phase response are associated , independent of weight loss , with survival duration in advanced gastrointestinal cancer patients Summary Background Local recurrence rates in operable rectal cancer are improved by radiotherapy ( with or without chemotherapy ) and surgical techniques such as total mesorectal excision . However , the contributions of surgery and radiotherapy to outcomes are unclear . We assessed the effect of the involvement of the circumferential resection margin and the plane of surgery achieved . Methods In this prospect i ve study , the plane of surgery achieved and the involvement of the circumferential resection margin were assessed by local pathologists , using a st and ard pathological protocol in 1156 patients with operable rectal cancer from the CR07 and NCIC-CTG CO16 trial , which compared short-course ( 5 days ) preoperative radiotherapy and selective postoperative chemoradiotherapy , between March , 1998 , and August , 2005 . All analyses were by intention to treat . This trial is registered , number IS RCT N 28785842 . Findings 128 patients ( 11 % ) had involvement of the circumferential resection margin , and the plane of surgery achieved was classified as good ( mesorectal ) in 604 ( 52 % ) , intermediate ( intramesorectal ) in 398 ( 34 % ) , and poor ( muscularis propria plane ) in 154 ( 13 % ) . We found that both a negative circumferential resection margin and a superior plane of surgery achieved were associated with low local recurrence rates . Hazard ratio ( HR ) was 0·32 ( 95 % CI 0·16–0·63 , p=0·0011 ) with 3-year local recurrence rates of 6 % ( 5–8 % ) and 17 % ( 10–26 % ) for patients who were negative and positive for circumferential resection margin , respectively . For plane of surgery achieved , HRs for mesorectal and intramesorectal groups compared with the muscularis propria group were 0·32 ( 0·16–0·64 ) and 0·48 ( 0·25–0·93 ) , respectively . At 3 years , the estimated local recurrence rates were 4 % ( 3–6 % ) for mesorectal , 7 % ( 5–11 % ) for intramesorectal , and 13 % ( 8–21 % ) for muscularis propria groups . The benefit of short-course preoperative radiotherapy did not differ in the three plane of surgery groups ( p=0·30 for trend ) . Patients in the short-course preoperative radiotherapy group who had a resection in the mesorectal plane had a 3-year local recurrence rate of only 1 % . Interpretation In rectal cancer , the plane of surgery achieved is an important prognostic factor for local recurrence . Short-course preoperative radiotherapy reduced the rate of local recurrence for all three plane of surgery groups , almost abolishing local recurrence in short-course preoperative radiotherapy patients who had a resection in the mesorectal plane . The plane of surgery achieved should therefore be assessed and reported routinely . Funding Medical Research Council ( UK ) and the National Cancer Institute of Canada Background and purpose Previous studies have shown that physical inactivity and obesity are risk factors for the development of colorectal cancer . However , controversy exists regarding the influence of these factors on survival in colorectal cancer patients . We evaluated the impact of recreational physical activity and body mass index ( BMI ) before and after colorectal cancer diagnosis on disease-specific mortality and all-cause mortality . Patients and methods This prospect i ve cohort study included 1,339 women enrolled in the Women ’s Health Initiative study who were diagnosed with colorectal cancer subsequent to study enrollment . BMI and recreational physical activity were measured before cancer diagnosis \n Output:\n " }, { "from": "agent", "value": "Both obese and underweight patients with colorectal cancer have an increased risk of all-cause mortality , cancer-specific mortality , disease recurrence and worse disease-free survival compared to normal weight patients" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Background : We conducted a prospect i ve trial r and omizing 75 physicians to either a control or intervention arm to evaluate the impact of providing patient-reported information on anxiety and other mental health symptoms and disorders to primary care physicians . Methods : Five hundred seventy-three patients of the study physicians who met entry criteria were r and omized to either usual care or usual care supplemented with feedback of patient-reported mental health information to physicians . This mental health information was derived from initial patient-reported question naires completed in waiting rooms of physicians contracted to a mixed-model health maintenance organization in Colorado . Main outcome measures included impact of intervention on rates of ( 1 ) chart notation of anxiety , depression , or other mental health diagnoses or symptoms ; ( 2 ) referral to mental health specialists ; ( 3 ) prescription of psychotropic medications ; ( 4 ) hospitalization ; and ( 5 ) office visits during a 5-month observation period . Results : Physicians receiving feedback on previously unrecognized and untreated anxiety patients were more likely to make chart notations ( adjusted odds ratio [ AOR ] = 2.51 , 95 percent confidence interval [ CI ] = 1.62 - 3.87 ) , to make referrals to mental health specialists ( AOR = 3.86 , 95 percent CI = 1.63 - 9.16 ) , and to see patients for more frequent outpatient visits ( AOR = 1.73 , 95 percent CI = 1.11 - 2.70 ) . Use of psychotropic medications and rate of hospitalizations did not differ significantly . Conclusions : Providing patient-reported mental health information to primary care physicians result ed in increased recognition and referral rates for previously unrecognized and untreated anxiety patients , plus an increase in primary care visits , without concomitant increases in the use of psychotropic medications or rate of hospitalizations BACKGROUND To date , the monitoring of patient progress using st and ardized assessment s has been neglected in hospital-based psychiatric care . Findings in outpatient psychotherapy have demonstrated clinical ly significant benefits for providing feedback to the sizeable minority of patients who were otherwise unlikely to experience positive outcome ( Lambert , 2007 ) . However , a similar system for presenting feedback on patient progress has not yet been assessed for group therapy within psychiatric inpatient setting s. The current study aim ed to develop and evaluate the effectiveness of a feedback system suitable for use in psychiatric services . METHODS In a nonr and omized trial , 1308 consecutive in patients and day patients , whose diagnoses were primarily depressive and anxiety disorders , completed the World Health Organization 's Wellbeing Index ( WHO-5 ) routinely during a ten-day cognitive behavioral therapy group . The first cohort ( n=461 ) received treatment as usual . The second cohort ( n=439 ) completed monitoring measures without feedback , and for patients in the third cohort ( n=408 ) , feedback on progress was provided to both clinicians and patients midway through the treatment period . RESULTS Feedback was effective in reducing depressive symptoms ( F(1,649)=6.29 , p<.05 ) for those patients at risk of poor outcome , but not effective in improving wellbeing ( F(1,569)=1.14 , p>.05 ) . LIMITATIONS The current findings may be generalized to patient sample s that exhibit largely depressive disorders , however rigorous follow-up is warranted . CONCLUSIONS Similar to outpatient setting s , feedback appears to be beneficial for improving symptom outcomes but further time may be required for wellbeing to be affected OBJECTIVE To examine dem and characteristics , social desirability on clients ' rating of working alliance using the Session Rating Scale ( SRS ; Miller , Duncan , & Johnson , 2000 ) . METHOD Clients ( N = 102 ) at two sites were r and omly assigned to one of three alliance feedback conditions : ( a ) IF -- SRS completed in presence of therapist and the results discussed immediately afterward ; ( b ) Next Session Feedback -- SRS completed alone and results discussed next session ; or ( c ) No Feedback -- SRS completed alone and results not available to therapist . Clients completed the SRS for the first three sessions of treatment . RESULTS No statistically significant differences in SRS scores across the feedback conditions were found . Additionally , the analysis showed that SRS scores were not correlated with a measure of social desirability but were correlated with an established alliance measure . CONCLUSIONS The results indicate that alliance scores were not inflated due to the presence of a therapist or knowing that the scores would be observed by the therapist Abstract Background Shared Decision Making ( SDM ) is a way to empower patients when decisions are made about treatment . In order to be effective agents in this process , patients need access to information of good quality . Routine Outcome Monitoring ( ROM ) may provide such information and therefore may be a key element in SDM . This trial tests the effectiveness of SDM using ROM , primarily aim ing to diminish decisional conflict of the patient while making decisions about treatment . The degree of decisional conflict , the primary outcome of this study , encompasses personal certainty about choosing an appropriate treatment , information about options , clarification of patient values , support from others and patients experience of an effective decision making process . Secondary outcomes of the study focus on the working alliance between patient and clinician , adherence to treatment , and clinical outcome and quality of life . Methods / Design This article presents the study protocol of a multi-centre two-arm cluster r and omised controlled trial ( RCT ) . The research is conducted in Dutch specialised mental health care teams participating in the ROM Quality Improvement Collaborative ( QIC ) , which aims to implement ROM in daily clinical practice . In the intervention teams , ROM is used as a source of information during the SDM process between the patient and clinician . Control teams receive no specific SDM or ROM instructions and apply decision making as usual . R and omisation is conducted at the level of the participating teams within the mental health organisations . A total of 12 teams from 4 organisations and 364 patients participate in the study . Prior to data collection , the intervention teams are trained to use ROM during the SDM process . Data collection will be at baseline , and at 3 and 6 months after inclusion of the patient . Control teams will implement the SDM and ROM model after completion of the study . Discussion This study will provide useful information about the effectiveness of ROM within a SDM framework . Furthermore , with practical guidelines this study may contribute to the implementation of SDM using ROM in mental health care . Reporting of the results is expected from December 2016 onwards . Trial registration Dutch trial register : TC5262 Trial registration date : 24th of June Background The main aim was to investigate the effect of using two brief feedback scales in mental health out-patient treatment six weeks after starting treatment , compared to treatment as usual . Hypotheses were that use of feedback scales would improve treatment alliance and patient satisfaction . Methods An open parallel-group r and omised controlled trial was conducted in an out-patient unit in a mental health hospital in Central Norway . Eight therapists trained in using the feedback scales in the Partners for Change Outcome Management System ( PCOMS ) treated the intervention group . Seventeen therapists treated the controls , providing treatment without using feedback scales . The main outcome measures were treatment alliance and patient satisfaction . Results Seventy-five patients participated . There were no differences between the groups in the intention to treat ( ITT ) analyses on alliance ( mean difference = 0.08 , 95 % CI −0.44 , 0.59 , p = 0.760 ) or satisfaction ( mean difference = 0.24 , 95 % CI −1.85 , 2.32 , p = 0.819 ) , and no statistically significant differences between the groups in the per protocol ( PP , n = 58 ) analyses on alliance ( mean difference = 0.32 , 95 % CI −0.84 , 3.16 , p = 0.137 ) or satisfaction ( mean difference = 1.16 , 95 % CI −0.84 , 3.16 , p = 0.248 ) six weeks after the treatment started . The effect size in favour of the PCOMS group increased from 0.07 for alliance and 0.06 for satisfaction in the intention to treat analysis to 0.40 on alliance and 0.31 for satisfaction in the per protocol analysis . Among the other outcomes , the PCOMS group had better motivation for treatment ( estimated mean difference ITT : 0.29 , 95 % CI 0.00 to 0.57 , p = 0.05 , PP : 0.28 , 95 % CI 0.04 , 0.52 , p = 0.024 ) . ConclusionS ix weeks after starting treatment , there were no effects on alliance and satisfaction from using two brief feedback scales . Since the per protocol analyses showed higher effect sizes , future investigations in a larger study with longer follow-up are warranted Abstract The current study examined the effects of providing treatment progress information and problem-solving tools to both patients and therapists during the course of psychotherapy . Three hundred and seventy patients were r and omly assigned to one of two treatment groups : treatment-as-usual , or an experimental condition based on the use of patient/therapist feedback and clinical decision-support tools . Patients in the feedback condition were significantly more improved at termination than the patients in the treatment-as-usual condition . Treatment effects were not a consequence of different amounts of psychotherapy received by experimental and control clients . These findings are consistent with past research on these approaches although the effect size was smaller in this study . Not all therapists were aided by the feedback intervention BACKGROUND Patient-clinician communication is central to mental healthcare but neglected in research . AIMS To test a new computer-mediated intervention structuring patient-clinician dialogue ( DIALOG ) focusing on patients ' quality of life and needs for care . METHOD In a cluster r and omised controlled trial , 134 keyworkers in six countries were allocated to DIALOG or treatment as usual ; 507 people with schizophrenia or related disorders were included . Every 2 months for 1 year , clinicians asked patients to rate satisfaction with quality of life and treatment , and request additional or different support . Responses were fed back immediately in screen displays , compared with previous ratings and discussed . Primary outcome was subjective quality of life , and secondary outcomes were unmet needs and treatment satisfaction . RESULTS Of 507 patients , 56 were lost to follow-up and 451 were included in intention-to-treat analyses . Patients receiving the DIALOG intervention had better subjective quality of life , fewer unmet needs and higher treatment satisfaction after 12 months . CONCLUSIONS Structuring patient-clinician dialogue to focus on patients ' views positively influenced quality of life , needs for care and treatment satisfaction OBJECTIVE To investigate the long-term effect on mental health symptoms and patient activation , from using the Partners for Change Outcome Management System ( PCOMS ) feedback scales in out-patient mental health consultations , compared to not using feedback scales . METHODS An open parallel-group r and omised controlled trial was conducted in a mental health hospital in Norway . Eight therapists treated the intervention group , using two feedback scales , and seventeen therapists treated the treatment as usual group . RESULTS Seventy-five patients participated . Six and twelve months after starting treatment there were no significant effects on the primary outcomes mental health symptoms or patient activation . Compared to baseline assessment the PCOMS group had significantly improved their patient activation scores after twelve months . CONCLUSION We found no long-term effects from using the PCOMS scales on mental health symptoms or patient activation . PRACTICE IMPLICATION S This study shows that the use of a feedback system does not increase mental health outcomes or patient activation Abstract Objective : To test the effectiveness of two programmes to improve the treatment of acute depression in primary care . Design : R and omised trial . Setting : Primary care clinics in Seattle . Patients : 613 patients starting antidepressant treatment . Intervention : Patients were r and omly assigned to continued usual care or one of two interventions : feedback only and feedback plus care management . Feedback only comprised feedback and algorithm based recommendations to doctors on the basis of data from computerised records of pharmacy and visits . Feedback plus care management included systematic follow up by telephone , sophisticated treatment recommendations , and practice support by a care manager . Main outcome measures : Blinded interviews by telephone 3 and 6 months after the initial prescription included a 20 item depression scale from the Hopkins symptom checklist and the structured clinical interview for the current DSM-IV depression module . Visits , antidepressant prescriptions , and overall use of health care were assessed from computerised records . Results : Compared with usual care , feedback only had no significant effect on treatment received or patient outcomes . Patients receiving feedback plus care management had a higher probability of both receiving at least moderate doses of antidepressants ( odds ratio 1.99 , 95 % confidence interval 1.23 to 3.22 ) and a 50 % improvement in depression scores on the symptom checklist ( 2.22 , 1.31 to 3.75 ) , lower mean depression scores on the symptom checklist at follow up , and a lower probability of major depression at follow up ( 0.46 , 0.24 to 0.86 ) . The incremental cost of feedback plus care management was about $ 80 ( £ 50 ) per patient . Conclusions : Monitoring and feedback to doctors yielded no significant benefits for patients in primary care starting antidepressant treatment . A programme of systematic follow up and care management by telephone , however , significantly improved outcomes at modest cost Abstract Aim : The objective of the study was to evaluate the efficacy of the Outcome Question naire 45 ( OQ-45 ) with feedback in a Swedish psychiatric outpatient population using a r and omized controlled design . Method : In all 1720 patients made at least one regular visit to the clinics in the period 12 February 2007 to 10 February 2008 and received information about the study . Of these , 374 patients ( 22 % ) agreed to participate . After written consent , 188 patients were r and omized to the feedback group and 1 \n Output:\n " }, { "from": "agent", "value": "We found insufficient evidence to support the use of routine outcome monitoring using PROMs in the treatment of CMHDs , in terms of improving patient outcomes or in improving management .\nThe findings are subject to considerable uncertainty however , due to the high risk of bias in the large majority of trials meeting the inclusion criteria , which means further research is very likely to have an important impact on the estimate of effect and is likely to change the estimate ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Background Reports indicate that the administration of epidural analgesia for pain relief during labor interferes with labor and increases cesarean deliveries . However , only a few controlled trials have assessed the effect of epidural analgesia on the incidence of cesarean delivery . The authors ' primary purpose in this r and omized study was to evaluate the effects of epidural analgesia on the rate of cesarean deliveries by providing a suitable alternative : patient-controlled intravenous analgesia . Methods Seven hundred fifteen women of mixed parity in spontaneous labor at full term were r and omly assigned to receive either epidural analgesia or patient-controlled intravenous meperidine analgesia . Epidural analgesia was maintained with a continuous epidural infusion of 0.125 % bupivacaine with 2 micro gram/ml fentanyl . Patient-controlled analgesia was maintained with 10 - 15 mg meperidine given every 10 min as needed using a patient-controlled pump . Procedures recorded in a manual that prescribed the intrapartum management were followed for each woman r and omized in the study . Results A total of 358 women were r and omized to receive epidural analgesia , and 243 ( 68 % ) of these women complied with the epidural analgesia protocol . Similarly , 357 women were r and omized to receive patient-controlled intravenous meperidine analgesia , and 259 ( 73 % ) of these women complied with the patient-controlled intravenous analgesia protocol . Only five women who were r and omized and received patient-controlled intravenous meperidine analgesia according to the protocol crossed over to epidural analgesia due to inadequate pain relief . There was no difference in the rate of cesarean deliveries between the two analgesia groups using intention-to-treat analysis based on the original r and omization ( epidural analgesia , 4 % [ 95 % CI : 1.9 - 6.2 % ] compared with patient-controlled intravenous analgesia , 5 % [ 95 % CI : 2.6 - 7.2 % ] ) . Similar results were observed for the analysis of the protocol -compliant groups ( epidural analgesia , 5 % [ 95 % CI : 2.6 - 8.5 % ] compared with patient-controlled intravenous analgesia , 6 % [ 95 % CI : 3 - 8.9 % ] ) . Women who received epidural analgesia reported lower pain scores during labor and delivery compared with women who received patient-controlled intravenous analgesia . Conclusions Epidural analgesia was not associated with increased numbers of cesarean delivery when compared with a suitable alternative method of analgesia OBJECTIVE This study was undertaken to determine whether a policy of delayed pushing for nulliparous women with continuous-infusion epidural analgesia reduces the risk of difficult delivery ( cesarean delivery , operative delivery from a midpelvic position , low-pelvic procedures with rotation > 45 degrees ) . STUDY DESIGN In this multicenter , r and omized , controlled trial women in the delayed pushing group ( n = 936 ) were advised to wait > or = 2 hours after full dilatation before commencement of pushing . Women in the early pushing group ( n = 926 ) were advised to commence pushing as soon as they had been r and omly assigned . RESULTS Difficult delivery was reduced with delayed pushing ( relative risk , 0.79 ; 95 % confidence interval , 0.66 - 0.95 ) . The greatest effect was on midpelvic procedures ( relative risk , 0.72 ; 95 % confidence interval , 0.55 - 0.93 ) . Although there was little evidence for an effect on low-pelvic procedures , spontaneous delivery was more frequent among women who practice d delayed pushing ( relative risk , 1.09 ; 95 % confidence interval , 1.00 - 1.18 ) . Abnormal umbilical cord blood pH ( < 7.15 venous value or < 7.10 arterial value ) was more frequent in the delayed pushing group ( relative risk , 2.45 , 95 % confidence interval , 1.35 - 4 . 43 ) . However , scores for a summary indicator , the Neonatal Morbidity Index , were similarly distributed in the 2 groups . CONCLUSION Delayed pushing is an effective strategy to reduce difficult deliveries among nulliparous women We compared the incidence of Caesarean delivery in nulliparous women r and omized to receive epidural analgesia with those r and omized to intramuscular ( i.m . ) pethidine . On admission to the delivery suite in established labour , 802 nulliparae had already agreed to be r and omized with respect to their first analgesia . One hundred and eighty-eight women required either no analgesia or 50 % nitrous oxide in oxygen ( Entonox ) only . Of the remaining 614 women , 310 were r and omly allocated to receive i.m . pethidine up to 300 mg and 304 to receive epidural bupivacaine . Labour management was st and ardized according to the criteria for active management of labour . The intention-to-treat analysis showed similar Caesarean section rates in those r and omized to epidural ( 12 % ) or pethidine analgesia ( 13 % ) . The difference in Caesarean rate was -1.1 % with 95 % confidence intervals from -6.3 % to + 4.1 % . The normal vaginal delivery rates were similar ( epidural , 59 % ; pethidine , 61 % ) The aim of this quasi‐experimental study was to examine the effects of maternal pethidine during labour on the developing breast feeding behaviour in infants in the first 2 h after birth compared with infants not exposed to pethidine . Forty‐four healthy infants were observed immediately after birth . They were placed skin‐to‐skin on their mothers ' chests . The development of mouth and sucking movements as well as rooting behaviour and state of sleep/wakefulness were noted . The observer was blind as to the pain relief the mother had received during labour . Of the 44 mothers 18 had received pethidine . The main findings were that infants exposed to pethidine had delayed and depressed sucking and rooting behaviour . In addition , a smaller proportion of infants exposed to pethidine started to suckle the breast . Rooting movements which are expected to be vigorous at 30 min after birth were affected both by administration of pethidine and a longer second stage of labour . It is suggested that the differences found in sucking behaviour may be a central effect of pethidine . Depression of rooting movements in the pethidine group may be caused by exhaustion due to a longer second stage of labour and administration of pethidine . It is recommended that pethidine‐exposed mother‐infant couples stay together after birth long enough to enable the infant to make the choice to attach or not to attach to the nipple without the forceful helping h and of the health staff Background Some studies suggest that epidural analgesia prolongs labor and increases the incidence of cesarean section , especially if it is administered before 5 cm cervical dilation . The purpose of the current study was to determine whether early administration of epidural analgesia affects obstetric outcome in nulliparous women who are receiving intravenous oxytocin . Methods Informed consent was obtained from healthy nulliparous women with a singleton fetus in a vertex presentation , who requested epidural analgesia while receiving intravenous oxytocin at at least 36 weeks ' gestation . Each patient was r and omized to receive either early or late epidural analgesia . R and omization occurred only after the following conditions were met : ( 1 ) the patient requested pain relief at that moment , ( 2 ) a lumbar epidural catheter had been placed , and ( 3 ) the cervix was at least 3 but less than 5 cm dilated . Patients in the early group immediately received epidural bupivacaine analgesia . Patients in the late group received 10 mg nalbuphlne intravenously . Late-group patients did not receive epidural analgesia until they achieved a cervical dilation of at least 5 cm or until at least 1 h had elapsed after a second dose of nalbuphine . Results Early administration of epidural analgesia did not prolong the interval between r and omization and the diagnosis of complete cervical dilation , and it did not increase the incidence of malposition of the vertex at delivery . Also , early administration of epidural analgesia did not result in an increased incidence of cesarean section or instrumental vaginal delivery . Thirteen ( 18 % ) of 74 women In the early group and 14 ( 19 % ) of 75 women in the late group underwent cesarean section ( relative risk for the early group 0.94 ; 95 % confidence interval 0.48–1.84 ) . Patients in the early group had lower pain scores between 30 and 120 min after r and omization , and were more likely to experience transient hypotension . Infants in the late group had lower umbilical arterial and venous blood pH and higher umbilical arterial and venous blood carbon dioxide tension measurements at delivery . Conclusions Early administration of epidural analgesia did not prolong labor or increase the incidence of operative delivery , when compared with intravenous nalbuphine followed by late administration of epidural analgesia , in nulliparous women who were receiving intravenous oxytocin Background : In 1981 , with support from the American Society of Anesthesiologists and the American College of Obstetricians and Gynecologists , anesthesia and obstetric providers were surveyed to identify the personnel and methods used to provide obstetric anesthesia in the United States . The survey was exp and ed and repeated in 1992 with support from the same organizations . Methods : Comments and questions from the American Society of Anesthesiologists Committee on Obstetrical Anesthesia and the American College of Obstetricians and Gynecologists Committee on Obstetric Practice were added to the original survey instrument to include newer issues while allowing comparison with data from 1981 . Using the American Hospital Association registry of hospitals , hospitals were differentiated by number of births per year ( stratum I , > or= to 1,500 births ; stratum II , 500–1,499 births ; stratum III , < 500 births ) and by U.S. census region . A stratified r and om sample of hospitals was selected . Two copies of the survey were sent to the administrator of each hospital , one for the chief of obstetrics and one for the chief of anesthesiology . Results : Compared with 1981 data , there was an overall reduction in the number of hospitals providing obstetric care ( from 4,163 to 3,545 ) , with the decrease occurring in the smallest units ( 56 % of stratum III hospitals in 1981 compared with 45 % in 1992 ) . More women received some type of labor analgesia , and there was a 100 % increase in the use of epidural analgesia . However , regional analgesia was unavailable in 20 % of the smallest hospitals . Spinal analgesia for labor was used in 4 % of parturients . In 1981 , obstetricians provided 30 % of epidural analgesia for labor ; they provided only 2 % in 1992 . Regional anesthesia was used for 78–85 % ( depending on strata ) of patients undergoing cesarean section , result ing in a marked decrease in the use of general anesthesia . Anesthesia for cesarean section was provided by nurse anesthetists without the medical direction of an anesthesiologist in only 4 % of stratum I hospitals but in 59 % of stratum III hospitals . Anesthesia personnel provided neonatal resuscitation in 10 % of cesarean deliveries compared with 23 % in 1981 . Conclusions : Compared with 1981 , analgesia is more often used by parturients during labor , and general anesthesia is used less often in patients having cesarean section deliveries . In the smallest hospitals , regional analgesia for labor is still unavailable to many parturients , and more than one half of anesthetics for cesarean section are provided by nurse anesthetists without medical direction by an anesthesiologist . Obstetricians are less likely to personally provide epidural analgesia for their patients . Anesthesia personnel are less involved in newborn resuscitation OBJECTIVE Intrathecal narcotics ( ITNs ) are being used in some setting s as a sole labor analgesic . However , they have not been directly compared to epidural analgesia . STUDY DESIGN We used a prospect i ve observational design . POPULATION Eighty-two women with uncomplicated full-term pregnancies were enrolled upon analgesia request during spontaneous labor with cervical dilation 3 to 7 cm . Sixty-three chose ITNs ( morphine and fentanyl ) , and 19 chose epidural analgesia ( continuous infusion of bupivacaine and fentanyl ) . OUTCOMES MEASURED Pain scores were documented using a visual analog scale . Satisfaction and side effects were rated with Likert scales during a structured interview on the first postpartum day . Outcomes were analyzed with multivariate regression techniques . RESULTS Intrathecal narcotics were associated with significantly higher pain scores than was epidural analgesia during the first and second stages of labor and on an overall postpartum rating . The median effective duration of action for ITNs was between 60 and 120 minutes ; however , ITNs provided excellent analgesia for a subgroup of women who delivered within 2 to 3 hours of receiving them . Although women in both groups were satisfied with their pain management , women receiving ITNs had statistically lower overall satisfaction scores . CONCLUSIONS Within the limitations of a nonr and omized study , a single intrathecal injection of \n Output:\n " }, { "from": "agent", "value": "Parenteral opioids provide modest pain relief in labor , and little evidence supports the use of one agent over another .\nAlthough epidural analgesia is the most effective form of pain relief , its use is associated with a longer labor , an increased incidence of maternal fever , and increased rates of operative vaginal delivery .\nThe effect of epidural analgesia on rates of cesarean delivery is controversial .\nNitrous oxide provides a modest analgesic effect , but it is used less often in the United States than in other developed nations .\nParacervical block provides effective analgesia in the first stage of labor , but its use is limited by postblock bradycardia ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: OBJECTIVE To investigate the utility of r and om anti-Müllerian hormone ( AMH ) in assessing ovarian response among women with diminished ovarian reserve ( DOR ) diagnosed by elevated early follicular-phase FSH levels . DESIGN Retrospective study . SETTING Academic and academically affiliated assisted reproductive technology ( ART ) programs . PATIENT(S ) Seventy-three women undergoing ART with elevated early follicular FSH levels . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) Number of oocytes retrieved during ART cycle , number of day 3 embryos , and cycle cancellation and clinical pregnancy rates . RESULT ( S ) R and om AMH levels were strongly correlated with the number of oocytes retrieved during an ART cycle among women with elevated FSH ( r=0.55 ) . Women with elevated FSH who had a r and om serum AMH level of 0.6 ng/mL or higher had twice the number of oocytes retrieved ( 11±1.3 vs. 5.6±0.6 ) , a greater number of day 3 embryos ( 5.7±0.9 vs. 3±0.5 ) , and approximately a third of the cycle cancellation rate ( 14 % vs. 41 % ) compared with women with a r and om serum AMH below 0.6 ng/mL. The clinical pregnancy rate was also higher among women with a r and om serum AMH≥0.6 ng/mL ( 28 % vs. 14 % ) , however , the difference was not statistically significant . CONCLUSION ( S ) A r and om serum AMH level is useful in setting expectations for ART prognosis in women with elevated early follicular-phase serum FSH levels OBJECTIVE To evaluate the relationship between serum anti-Müllerian hormone ( AMH ) and antral follicle size , and to ascertain which cohort of antral follicles is most predictive of the response to controlled ovarian stimulation during assisted reproduction treatment ( ART ) . DESIGN Prospect i ve study . SETTING University-based Assisted Conception Unit . PATIENT(S ) One hundred thirteen women undergoing first cycle of ART . INTERVENTION(S ) Transvaginal 3D-ultrasound assessment and venipuncture in the early-follicular phase of the menstrual cycle . MAIN OUTCOME MEASURE(S ) Serum AMH levels , number of mature oocytes retrieved and poor ovarian response . RESULT ( S ) The antral follicle cohorts measuring 2 to 3 mm , > 3 to 4 mm , > 4 to 5 mm , and > 5 to 6 mm were most significantly correlated with AMH ( r = .30 , .27 , .30 , and .41 , respectively ) and the number of mature oocytes retrieved ( r = .28 , .23 , .29 , and .34 , respectively ) . Although these follicle cohorts of 2 - 6 mm were significant predictors of the number of mature oocytes retrieved on regression analysis , their discriminative ability ( area under the curve [ AUC ] : 0.829 ) for the prediction of poor ovarian response was similar to total counts made using cohorts of 2 to 4 mm , 2 to 5 mm , 2 to 8 mm , and 2 to 10 mm ( AUCs : 0.794 , 0.812 , 0.852 , and 0.826 , respectively ) . CONCLUSION ( S ) The number of antral follicles measuring 2 to 6 mm is most reflective of the quantitative ovarian reserve . However , the ability of this group of antral follicles to predict poor ovarian response appears similar to that of the follicular cohorts of 2 to 4 mm , 2 to 5 mm , 2 to 8 mm , and 2 to 10 mm BACKGROUND Diminished ovarian reserve has become a major cause of infertility . Anti-Mullerian hormone ( AMH ) seems to be a promising c and i date to assess ovarian reserve and predict the response to controlled ovarian hyperstimulation ( COH ) . This prospect i ve study was conducted to evaluate the relevance of AMH in a routine IVF program . METHODS Three hundred and sixteen patients were prospect ively enrolled to enter their first IVF/ICSI-cycle . Age , FSH- , inhibin B- and AMH-levels and their predictive values for ovarian response and clinical pregnancy rate were compared by discriminant analyses . RESULTS A total of 132 oocyte retrievals were performed . A calculated cut-off level < or = 1.26 ng/ml AMH alone detected poor responders ( < or = 4 oocytes ) with a sensitivity of 97 % , and there was a 98 % correct prediction of normal response in COH if levels were above this threshold . With levels < 0.5 ng/ml , a correct prediction of very poor response ( < or = 2 oocytes ) was possible in 88 % of cases . Levels of AMH > or = 0.5 ng/ml were not significantly correlated with clinical pregnancy rates . CONCLUSIONS AMH is a predictor of ovarian response and suitable for screening . Levels < or = 1.26 ng/ml are highly predictive of reduced ovarian reserve and should be confirmed by a second line antral follicle count . Measurement of AMH supports clinical decisions , but alone it is not a suitable predictor of IVF success BACKGROUND Anti-Müllerian hormone ( AMH ) is produced by the granulosa cells of preantral and small antral follicles and its levels can be assessed in serum . Since the number of ovarian follicles declines with increasing age , AMH levels might be used as a marker for ovarian ageing . Therefore , we studied the relationship between AMH levels and ovarian response during ovarian stimulation for IVF . METHODS A total of 130 patients undergoing their first IVF treatment cycle using a long protocol with GnRH agonist was prospect ively included . Blood withdrawal was performed and the number of antral follicles was assessed by ultrasound on day 3 of a spontaneous cycle . Poor response and the number of oocytes were used as primary outcome measures . In a r and om subset of 23 patients a GnRH agonist stimulation test was performed to investigate whether a rise in FSH and LH would affect AMH levels . RESULTS The data of 119 patients were analysed . Serum AMH levels were highly correlated with the number of antral follicles ( r = 0.77 ; P < 0.01 ) and the number of oocytes retrieved ( r = 0.57 , P < 0.01 ) . A negative association was found between AMH levels and poor ovarian response ( fewer than 4 oocytes or cycle cancellation ; OR 0.82 , 95 % CI 0.75 - 0.90 , P < 0.01 ) . Inclusion of inhibin B and FSH concentrations to AMH in a multivariate model improved the prediction of ovarian response . The post GnRH agonist rise in FSH and LH levels did not influence AMH values . CONCLUSIONS Poor response in IVF , indicative of a diminished ovarian reserve , is associated with reduced baseline serum AMH concentrations . In line with recent observations it appears that AMH can be used as a marker for ovarian ageing BACKGROUND Individualization of controlled ovarian stimulation ( COS ) for assisted conception is complicated by variable ovarian response to follicle stimulating hormone . We hypothesized that anti-Müllerian hormone ( AMH ) , a predictor of oocyte yield , may facilitate treatment strategies for women undergoing COS , to optimize safety and clinical pregnancy rates . METHODS Prospect i ve cohort study of 538 patients in two centres with differential COS strategies based on a central ized AMH measurement . RESULTS AMH was associated with oocyte yield after ovarian stimulation in both centres , and a ' reduced ' AMH ( 1 to < 5 pmol/l ) was associated with a reduced clinical pregnancy rate . Women with a ' normal ' AMH ( 5 to < 15 pmol/l ) treated with a long GnRH-agonist protocol ( both centres ) showed a low incidence of excess response ( 0 % ) and poor response ( 0 % ) . In women with ' high ' AMH ( > 15 pmol/l ) , the antagonist protocol eliminated the need for complete cryopreservation of embryos due to excess response ( P < 0.001 ) and showed a higher fresh cycle clinical pregnancy rate than agonist cycles [ OR 4.40 ( 95 % CI 1.95 - 9.93 ) , P < 0.001 ] . CONCLUSIONS The use of circulating AMH to individualize treatment strategies for COS may result in reduced clinical risk , optimized treatment burden and maintained pregnancy rates , and is worthy of prospect i ve r and omized examination Purpose To evaluate the efficacy of GnRH antagonist in comparison with the GnRH agonist protocol in OCP pretreated polycystic ovary syndrome ( PCOs ) patients undergoing their first ART cycle . Material s and methods Prospect i ve r and omized controlled trial . University-based tertiary fertility center . Ninety-five PCOs patients under 35 years of age , with primary infertility were r and omized to an ovarian stimulation protocol consisting of either . GnRh antagonist ( study group ) or GnRH agonist ( control group ) after pretreatment with OCP . Coasting or GnRH agonist Trigger was used when estradiol level ≥3,000 pgr/ml in the control and study group , respectively . Both groups received 800 mg vaginal progesterone and 4 mg oral estradiol valerate for luteal phase support . Results There was no statistically significant difference in the age , body mass index , basal FSH , duration of infertility , the number of oocytes retrieved , the number of embryos transferred , Serum E2 levels on day of trigger , fertilization rate , chemical and clinical pregnancy rates between the two groups . None of the patients in the study group developed ovarian hyperstimulation syndrome ( OHSS ) compared with 22.2 % of patients in the control group . Total duration of treatment and the number of HMG ampoules used were lower in the study group . Conclusion Antagonist protocol and GnRH agonist trigger for ovulation whenever necessary has a similar cycle outcome to the GnRH-agonist protocol in OCP pretreated PCOs patients , with significantly reduced risk of OHSS BACKGROUND We evaluated basal and dynamic hormonal markers [ ( FSH , inhibin B , estradiol and anti-Mullerian hormone ( AMH ) ] during the follicular phase and luteal phase of the menstrual cycle and ultrasonic ovarian morphology as predictors of IVF outcome . METHODS Fifty-six women , aged < 38 years , with normal day 3 FSH levels were included prospect ively . Serum estradiol , inhibin B and AMH were measured before and 24 h after administration of 300 IU of recombinant FSH on cycle day 3 - 4 and during the luteal phase . Ovarian volume and antral follicle count ( AFC ) were evaluated on cycle day 3 - 4 . The predictive value of oocyte number and pregnancy were assessed using uni- and multivariate analysis . RESULTS Poor responders ( < 6 oocytes ) had significantly lower luteal AMH levels , while high responders ( > 20 oocytes ) had significantly higher AFC , AMH and luteal stimulated inhibin B and estradiol than normal responders . Multivariate regression analyses showed that the best models for predicting oocyte number included AFC , follicular phase AMH and stimulated inhibin B. Only AMH showed a significant difference between pregnant and non-pregnant women at both cycle phases . CONCLUSIONS In young women ( < 38 years ) , AFC or basal AMH and stimulated inhibin B predict ovarian response for IVF . The only predictor for pregnancy is follicular or luteal phase AMH BACKGROUND Women with polycystic ovary syndrome ( PCOS ) are at risk of developing ovarian hyperstimulation syndrome ( OHSS ) during ovarian stimulation . Use of GnRH antagonist in the general subfertile population is associated with lower incidence of OHSS than agonists and similar probability of live birth but it is unclear if this is true for patients with PCOS . Our aim was to compare the flexible GnRH antagonist and GnRH agonist long protocol s in patients with PCOS undergoing IVF ( primary end-point : ongoing pregnancy rate per patient r and omized ) . METHODS In this r and omised controlled trial ( RCT ) , 220 patients with PCOS were r and omly allocated in two groups : long GnRH agonist down-regulation protocol ( n = 110 ) and flexible GnRH antagonist protocol ( n = 110 ) . RESULTS No differences were observed in ongoing pregnancy rates [ 50.9 versus 47.3 % , difference 3.6 % , 95 % confidence interval ( CI ) : -9.6 to + 16.8 % ] in the agonist and antagonist protocol s , respectively . Incidence of OHSS Grade II was lower in the antagonist compared with agonist group ( 40.0 versus 60.0 % , difference -20.0 % , 95 % CI : -7.1 to -32.9 % , P < 0.01 ) . Duration of stimulation ( 10 versus 12 days , difference 2 days , 95 % CI : + 1 to + 2 \n Output:\n " }, { "from": "agent", "value": "The selection of the appropriate and individualized gonadotrophin dose is also of paramount importance for effective COS and subsequent IVF outcomes .\nPersonalized IVF offers several benefits ; it enables clinicians to give women more accurate information on their prognosis thus facilitating counselling especially in cases of extremes of ovarian response ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Purpose Pasireotide ( SOM230 ) , a novel multireceptor lig and somatostatin analog ( SSA ) , binds with high affinity to four of the five somatostatin receptor subtypes ( sst1–3 , 5 ) . This study evaluated the safety , tolerability , pharmacokinetics , and pharmacodynamics profiles of pasireotide long-acting release ( LAR ) formulation in patients with advanced gastroenteropancreatic neuroendocrine tumor ( GEP NET ) refractory to other SSAs . Methods In this r and omized , multicenter , open-label , phase II study , patients with biopsy-proven primary or metastatic GEP NET refractory to available SSAs were r and omly assigned 1:1:1 to receive pasireotide LAR by deep intragluteal injection at a dose of 20 , 40 , or 60 mg once every 28 days for 3 months . Results Forty-two patients received pasireotide LAR . Adverse events were reported by 34 ( 81 % ) patients , with the most frequently reported including diarrhea , fatigue , abdominal pain , and nausea . Mean fasting glucose levels were increased compared with baseline at all points throughout the study . After the third injection of pasireotide LAR , the median trough plasma concentrations on day 84 were 4.82 , 12.0 , and 19.7 ng/mL in the 20- , 40- , and 60-mg treatment groups , respectively . Drug accumulation was limited for each dose based on the increase in trough concentrations after the first to third injections ( accumulation ratios were approximately 1 from all dose levels ) . Conclusions This study demonstrated that a new , once-monthly , intramuscular LAR formulation of pasireotide was well tolerated in patients with advanced GEP NET . Steady state levels of plasma pasireotide were achieved after three injections To evaluate the treatment of advanced islet-cell carcinoma , we r and omly assigned 84 patients to streptozocin alone or streptozocin plus fluorouracil . Each regimen was given in five-day courses . The most frequent toxic effects were nausea and vomiting , mild and reversible renal toxicity , and bone-marrow depression with the combination regimen . The combination had advantages over streptozocin alone in overall rate of response ( 63 vs. 36 per cent ) and in rates of complete response ( 33 vs. 12 per cent ) . There was no evidence of a preferential response among types of functional tumors . Objective responses were generally of long duration ( median , 17 months ) and of substantive clinical benefit . Treatment with the combination also yielded a survival advantage over treatment with streptozocin alone ( medians , 26 and 16 1/2 months ) , but this difference is not statistically significant . In spite of gastrointestinal side effects , streptozocin combined with fluorouracil appears to be a valuable treatment for advanced islet-cell carcinoma Background Several studies have demonstrated the antitumor activity of first-generation somatostatin analogs ( SSAs ) , primarily targeting somatostatin receptor ( sstr ) subtypes 2 and 5 , in neuroendocrine tumors ( NET ) . Pasireotide , a second-generation SSA , targets multiple sstr subtypes . We compared the efficacy and safety of pasireotide plus everolimus to everolimus alone in patients with advanced , well-differentiated , progressive pancreatic NET . Patients and methods Patients were r and omized 1 : 1 to receive a combination of everolimus ( 10 mg/day , orally ) and pasireotide long-acting release ( 60 mg/28 days , intramuscularly ) or everolimus alone ( 10 mg/day , orally ) ; stratified by prior SSA use , and baseline serum chromogranin A and neuron-specific enolase . The primary end point was progression-free survival ( PFS ) . Secondary end points included overall survival , objective response rate , disease control rate , and safety . Biomarker response was evaluated in an exploratory analysis . Results Of 160 patients enrolled , 79 were r and omized to the combination arm and 81 to the everolimus arm . Baseline demographics and disease characteristics were similar between the treatment arms . No significant difference was observed in PFS : 16.8 months in combination arm versus 16.6 months in everolimus arm ( hazard ratio , 0.99 ; 95 % confidence interval , 0.64 - 1.54 ) . Partial responses were observed in 20.3 % versus 6.2 % of patients in combination arm versus everolimus arm ; however , overall disease control rate was similar ( 77.2 % versus 82.7 % , respectively ) . No significant improvement was observed in median overall survival . Adverse events were consistent with the known safety profile of both the drugs ; grade 3 or 4 fasting hyperglycemia was seen in 37 % versus 11 % of patients , respectively . Conclusions The addition of pasireotide to everolimus was not associated with the improvement in PFS compared with everolimus alone in this study . Further studies to delineate mechanisms by which SSAs slow tumor growth in NET are warranted BACKGROUND Effective systemic therapies for patients with advanced , progressive neuroendocrine tumours of the lung or gastrointestinal tract are scarce . We aim ed to assess the efficacy and safety of everolimus compared with placebo in this patient population . METHODS In the r and omised , double-blind , placebo-controlled , phase 3 RADIANT-4 trial , adult patients ( aged ≥18 years ) with advanced , progressive , well-differentiated , non-functional neuroendocrine tumours of lung or gastrointestinal origin were enrolled from 97 centres in 25 countries worldwide . Eligible patients were r and omly assigned in a 2:1 ratio by an interactive voice response system to receive everolimus 10 mg per day orally or identical placebo , both with supportive care . Patients were stratified by tumour origin , performance status , and previous somatostatin analogue treatment . Patients , investigators , and the study sponsor were masked to treatment assignment . The primary endpoint was progression-free survival assessed by central radiology review , analysed by intention to treat . Overall survival was a key secondary endpoint . This trial is registered with Clinical Trials.gov , number NCT01524783 . FINDINGS Between April 3 , 2012 , and Aug 23 , 2013 , a total of 302 patients were enrolled , of whom 205 were allocated to everolimus 10 mg per day and 97 to placebo . Median progression-free survival was 11·0 months ( 95 % CI 9·2 - 13·3 ) in the everolimus group and 3·9 months ( 3·6 - 7·4 ) in the placebo group . Everolimus was associated with a 52 % reduction in the estimated risk of progression or death ( hazard ratio [ HR ] 0·48 [ 95 % CI 0·35 - 0·67 ] , p<0·00001 ) . Although not statistically significant , the results of the first pre-planned interim overall survival analysis indicated that everolimus might be associated with a reduction in the risk of death ( HR 0·64 [ 95 % CI 0·40 - 1·05 ] , one-sided p=0·037 , whereas the boundary for statistical significance was 0·0002 ) . Grade 3 or 4 drug-related adverse events were infrequent and included stomatitis ( in 18 [ 9 % ] of 202 patients in the everolimus group vs 0 of 98 in the placebo group ) , diarrhoea ( 15 [ 7 % ] vs 2 [ 2 % ] ) , infections ( 14 [ 7 % ] vs 0 ) , anaemia ( 8 [ 4 % ] vs 1 [ 1 % ] ) , fatigue ( 7 [ 3 % ] vs 1 [ 1 % ] ) , and hyperglycaemia ( 7 [ 3 % ] vs 0 ) . INTERPRETATION Treatment with everolimus was associated with significant improvement in progression-free survival in patients with progressive lung or gastrointestinal neuroendocrine tumours . The safety findings were consistent with the known side-effect profile of everolimus . Everolimus is the first targeted agent to show robust anti-tumour activity with acceptable tolerability across a broad range of neuroendocrine tumours , including those arising from the pancreas , lung , and gastrointestinal tract . FUNDING Novartis Pharmaceuticals Corporation BACKGROUND This was a two-stage , phase II trial of the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor BEZ235 in patients with everolimus-resistant pancreatic neuroendocrine tumours ( pNETs ) ( NCT01658436 ) . PATIENTS AND METHODS In stage 1 , 11 patients received 400 mg BEZ235 orally twice daily ( bid ) . Due to tolerability concerns , a further 20 patients received BEZ235 300 mg bid . Stage 2 would be triggered by a 16-week progression-free survival ( PFS ) rate of ≥60 % in stage 1 . RESULTS As of 30 June , 2014 , 29/31 patients had discontinued treatment . Treatment-related grade 3/4 adverse events were reported in eight ( 72.7 % ) patients at 400 mg and eight ( 40.0 % ) patients at 300 mg , including hyperglycaemia , diarrhoea , nausea , and vomiting . The estimated 16-week PFS rate was 51.6 % ( 90 % confidence interval=35.7 - 67.3 % ) . CONCLUSION BEZ235 was poorly tolerated by patients with everolimus-resistant pNETs at 400 and 300 mg bid doses . Although evidence of disease stability was observed , the study did not proceed to stage 2 BACKGROUND The multitargeted tyrosine kinase inhibitor sunitinib has shown activity against pancreatic neuroendocrine tumors in pre clinical models and phase 1 and 2 trials . METHODS We conducted a multinational , r and omized , double-blind , placebo-controlled phase 3 trial of sunitinib in patients with advanced , well-differentiated pancreatic neuroendocrine tumors . All patients had Response Evaluation Criteria in Solid Tumors-defined disease progression documented within 12 months before baseline . A total of 171 patients were r and omly assigned ( in a 1:1 ratio ) to receive best supportive care with either sunitinib at a dose of 37.5 mg per day or placebo . The primary end point was progression-free survival ; secondary end points included the objective response rate , overall survival , and safety . RESULTS The study was discontinued early , after the independent data and safety monitoring committee observed more serious adverse events and deaths in the placebo group as well as a difference in progression-free survival favoring sunitinib . Median progression-free survival was 11.4 months in the sunitinib group as compared with 5.5 months in the placebo group ( hazard ratio for progression or death , 0.42 ; 95 % confidence interval [ CI ] , 0.26 to 0.66 ; P<0.001 ) . A Cox proportional-hazards analysis of progression-free survival according to baseline characteristics favored sunitinib in all subgroups studied . The objective response rate was 9.3 % in the sunitinib group versus 0 % in the placebo group . At the data cutoff point , 9 deaths were reported in the sunitinib group ( 10 % ) versus 21 deaths in the placebo group ( 25 % ) ( hazard ratio for death , 0.41 ; 95 % CI , 0.19 to 0.89 ; P=0.02 ) . The most frequent adverse events in the sunitinib group were diarrhea , nausea , vomiting , asthenia , and fatigue . CONCLUSIONS Continuous daily administration of sunitinib at a dose of 37.5 mg improved progression-free survival , overall survival , and the objective response rate as compared with placebo among patients with advanced pancreatic neuroendocrine tumors . ( Funded by Pfizer ; Clinical Trials.gov number , NCT00428597 . ) Purpose Everolimus improved median progression-free survival by 6.4 months in patients with advanced pancreatic neuroendocrine tumors ( NET ) compared with placebo in the RADIANT-3 study . Here , we present the final overall survival ( OS ) data and data on the impact of biomarkers on OS from the RADIANT-3 study . Methods Patients with advanced , progressive , low- or intermediate- grade pancreatic NET were r and omly assigned to everolimus 10 mg/day ( n = 207 ) or placebo ( n = 203 ) . Crossover from placebo to open-label everolimus was allowed on disease progression . Ongoing patients were unblinded after final progression-free survival analysis and could transition to open-label everolimus at the investigator 's discretion ( extension phase ) . OS analysis was performed using a stratified log-rank test in the intent-to-treat population . The baseline levels of chromogranin A , neuron-specific enolase , and multiple soluble angiogenic biomarkers were determined and their impact on OS was explored . Results Of \n Output:\n " }, { "from": "agent", "value": "The experimental treatments led to increased incidence and risks of GI events compared to the control treatments ( P<0.05 ) .\nDiarrhea was the most common GI event .\nAdditionally , GI NETs led to higher risk of GI events than pancreatic NETs ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: BACKGROUND The relative efficacy of streptokinase and tissue plasminogen activator and the roles of intravenous as compared with subcutaneous heparin as adjunctive therapy in acute myocardial infa rct ion are unresolved questions . The current trial was design ed to compare new , aggressive thrombolytic strategies with st and ard thrombolytic regimens in the treatment of acute myocardial infa rct ion . Our hypothesis was that newer thrombolytic strategies that produce earlier and sustained reperfusion would improve survival . METHODS In 15 countries and 1081 hospitals , 41,021 patients with evolving myocardial infa rct ion were r and omly assigned to four different thrombolytic strategies , consisting of the use of streptokinase and subcutaneous heparin , streptokinase and intravenous heparin , accelerated tissue plasminogen activator ( t-PA ) and intravenous heparin , or a combination of streptokinase plus t-PA with intravenous heparin . ( \" Accelerated \" refers to the administration of t-PA over a period of 1 1/2 hours -- with two thirds of the dose given in the first 30 minutes -- rather than the conventional period of 3 hours . ) The primary end point was 30-day mortality . RESULTS The mortality rates in the four treatment groups were as follows : streptokinase and subcutaneous heparin , 7.2 percent ; streptokinase and intravenous heparin , 7.4 percent ; accelerated t-PA and intravenous heparin , 6.3 percent , and the combination of both thrombolytic agents with intravenous heparin , 7.0 percent . This represented a 14 percent reduction ( 95 percent confidence interval , 5.9 to 21.3 percent ) in mortality for accelerated t-PA as compared with the two streptokinase-only strategies ( P = 0.001 ) . The rates of hemorrhagic stroke were 0.49 percent , 0.54 percent , 0.72 percent , and 0.94 percent in the four groups , respectively , which represented a significant excess of hemorrhagic strokes for accelerated t-PA ( P = 0.03 ) and for the combination strategy ( P < 0.001 ) , as compared with streptokinase only . A combined end point of death or disabling stroke was significantly lower in the accelerated-tPA group than in the streptokinase-only groups ( 6.9 percent vs. 7.8 percent , P = 0.006 ) . CONCLUSIONS The findings of this large-scale trial indicate that accelerated t-PA given with intravenous heparin provides a survival benefit over previous st and ard thrombolytic regimens IMPORTANCE Data are limited regarding the association between CYP2C19 genetic variants and clinical outcomes of patients with minor stroke or transient ischemic attack treated with clopidogrel . OBJECTIVE To estimate the association between CYP2C19 genetic variants and clinical outcomes of clopidogrel-treated patients with minor stroke or transient ischemic attack . DESIGN , SETTING , AND PARTICIPANTS Three CYP2C19 major alleles ( * 2 , * 3 , * 17 ) were genotyped among 2933 Chinese patients from 73 sites who were enrolled in the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events ( CHANCE ) r and omized trial conducted from January 2 , 2010 , to March 20 , 2012 . INTERVENTIONS Patients with acute minor ischemic stroke or transient ischemic attack in the trial were r and omized to treatment with clopidogrel combined with aspirin or to aspirin alone . MAIN OUTCOMES AND MEASURES The primary efficacy outcome was new stroke . The secondary efficacy outcome was a composite of new composite vascular events ( ischemic stroke , hemorrhagic stroke , myocardial infa rct ion , or vascular death ) . Bleeding was the safety outcome . RESULTS Among 2933 patients , 1948 ( 66.4 % ) were men , with a mean age of 62.4 years . Overall , 1207 patients ( 41.2 % ) were noncarriers and 1726 patients ( 58.8 % ) were carriers of loss-of-function alleles ( * 2 , * 3 ) . After day 90 follow-up , clopidogrel-aspirin reduced the rate of new stroke in the noncarriers but not in the carriers of the loss-of-function alleles ( P = .02 for interaction ; events among noncarriers , 41 [ 6.7 % ] with clopidogrel-aspirin vs 74 [ 12.4 % ] with aspirin ; hazard ratio [ HR ] , 0.51 [ 95 % CI , 0.35 - 0.75 ] ; events among carriers , 80 [ 9.4 % ] with clopidogrel-aspirin vs 94 [ 10.8 % ] with aspirin ; HR , 0.93 [ 95 % CI , 0.69 to 1.26 ] ) . Similar results were observed for the secondary composite efficacy outcome ( noncarriers : 41 [ 6.7 % ] with clopidogrel-aspirin vs 75 [ 12.5 % ] with aspirin ; HR , 0.50 [ 95 % CI , 0.34 - 0.74 ] ; carriers : 80 [ 9.4 % ] with clopidogrel-aspirin vs 95 [ 10.9 % ] with aspirin ; HR , 0.92 [ 95 % CI , 0.68 - 1.24 ] ; P = .02 for interaction ) . The effect of treatment assignment on bleeding did not vary significantly between the carriers and the noncarriers of the loss-of-function alleles ( 2.3 % for carriers and 2.5 % for noncarriers in the clopidogrel-aspirin group vs 1.4 % for carriers and 1.7 % for noncarriers in the aspirin only group ; P = .78 for interaction ) . CONCLUSIONS AND RELEVANCE Among patients with minor ischemic stroke or transient ischemic attack , the use of clopidogrel plus aspirin compared with aspirin alone reduced the risk of a new stroke only in the subgroup of patients who were not carriers of the CYP2C19 loss-of-function alleles . These findings support a role of CYP2C19 genotype in the efficacy of this treatment . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00979589 OBJECT Symptomatic intracranial atherosclerotic disease ( ICAD ) has a high risk of recurrent stroke . Genetic polymorphisms in CYP2C19 and CES1 are associated with adverse outcomes in cardiovascular patients , but have not been studied in ICAD . The authors studied CYP2C19 and CES1 single-nucleotide polymorphisms ( SNPs ) in symptomatic ICAD patients . METHODS Genotype testing for CYP2C19 * 2 , (*)3 , (*)8 , (*)17 and CES1 G143E was performed on 188 adult symptomatic ICAD patients from 3 medical centers who were medically managed with clopidogrel and aspirin . Testing was performed prospect ively at 1 center , and retrospectively from a DNA sample biorepository at 2 centers . Multiple logistic regression and Cox regression analysis were performed to assess the association of these SNPs with the primary endpoint , which was a composite of transient ischemic attack ( TIA ) , stroke , myocardial infa rct ion , or death within 12 months . RESULTS The primary endpoint occurred in 14.9 % of the 188 cases . In multiple logistic regression analysis , the presence of the CYP2C19 loss of function ( LOF ) alleles * 2 , * 3 , and * 8 in the medically managed patients was associated with lower odds of primary endpoint compared with wild-type homozygotes ( odds ratio [ OR ] 0.13 , 95 % CI 0.03 - 0.62 , p = 0.0101 ) . Cox regression analysis demonstrated the CYP2C19 LOF carriers had a lower risk for the primary endpoint , with hazard ratio ( HR ) of 0.27 ( 95 % CI 0.08 - 0.95 ) , p = 0.041 . A sensitivity analysis of a secondary composite endpoint of TIA , stroke , or death demonstrated a significant trend in multiple logistic regression analysis of CYP2C19 variants , with lower odds of secondary endpoint in patients carrying at least 1 LOF allele ( * 2 , * 3 , * 8) than in wild-type homozygotes ( OR 0.27 , 95 % CI 0.06 - 1.16 , p = 0.078 ) . Cox regression analysis demonstrated that the carriers of CYP2C19 LOF alleles had a lower risk forthe secondary composite endpoint ( HR 0.22 , 95 % CI 0.05 - 1.04 , p = 0.056 ) . CONCLUSIONS This is the first study examining genetic variants and their effects in symptomatic ICAD . Variant alleles of CYP2C19 ( * 2 , * 3 , * 8) were associated with lower odds of the primary and secondary composite endpoints . However , the direction of the association was opposite of what is expected based on this SNP . This may reflect an incomplete underst and ing of this genetic variation and its effect in symptomatic ICAD and warrants further investigations BACKGROUND Many clinical trials have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of clinical thrombotic events . Aspirin and ticlopidine have been shown to be effective , but both have potentially serious adverse effects . Clopidogrel , a new thienopyridine derivative similar to ticlopidine , is an inhibitor of platelet aggregation induced by adenosine diphosphate . METHODS CAPRIE was a r and omised , blinded , international trial design ed to assess the relative efficacy of clopidogrel ( 75 mg once daily ) and aspirin ( 325 mg once daily ) in reducing the risk of a composite outcome cluster of ischaemic stroke , myocardial infa rct ion , or vascular death ; their relative safety was also assessed . The population studied comprised subgroups of patients with atherosclerotic vascular disease manifested as either recent ischaemic stroke , recent myocardial infa rct ion , or symptomatic peripheral arterial disease . Patients were followed for 1 to 3 years . FINDINGS 19,185 patients , with more than 6300 in each of the clinical subgroups , were recruited over 3 years , with a mean follow-up of 1.91 years . There were 1960 first events included in the outcome cluster on which an intention-to-treat analysis showed that patients treated with clopidogrel had an annual 5.32 % risk of ischaemic stroke , myocardial infa rct ion , or vascular death compared with 5.83 % with aspirin . These rates reflect a statistically significant ( p = 0.043 ) relative-risk reduction of 8.7 % in favour of clopidogrel ( 95 % Cl 0.3 - 16.5 ) . Corresponding on-treatment analysis yielded a relative-risk reduction of 9.4 % . There were no major differences in terms of safety . Reported adverse experiences in the clopidogrel and aspirin groups judged to be severe included rash ( 0.26 % vs 0.10 % ) , diarrhoea ( 0.23 % vs 0.11 % ) , upper gastrointestinal discomfort ( 0.97 % vs 1.22 % ) , intracranial haemorrhage ( 0.33 % vs 0.47 % ) , and gastrointestinal haemorrhage ( 0.52 % vs 0.72 % ) , respectively . There were ten ( 0.10 % ) patients in the clopidogrel group with significant reductions in neutrophils ( < 1.2 x 10(9)/L ) and 16 ( 0.17 % ) in the aspirin group . INTERPRETATION Long-term administration of clopidogrel to patients with atherosclerotic vascular disease is more effective than aspirin in reducing the combined risk of ischaemic stroke , myocardial infa rct ion , or vascular death . The overall safety profile of clopidogrel is at least as good as that of medium-dose aspirin BACKGROUND Stroke is common during the first few weeks after a transient ischemic attack ( TIA ) or minor ischemic stroke . Combination therapy with clopidogrel and aspirin may provide greater protection against subsequent stroke than aspirin alone . METHODS In a r and omized , double-blind , placebo-controlled trial conducted at 114 centers in China , we r and omly assigned 5170 patients within 24 hours after the onset of minor ischemic stroke or high-risk TIA to combination therapy with clopidogrel and aspirin ( clopidogrel at an initial dose of 300 mg , followed by 75 mg per day for 90 days , plus aspirin at a dose of 75 mg per day for the first 21 days ) or to placebo plus aspirin ( 75 mg per day for 90 days ) . All participants received open \n Output:\n " }, { "from": "agent", "value": "Conclusions : Carriers of CYP2C19 loss-of-function alleles are at greater risk of stroke and composite vascular events than noncarriers among patients with ischemic stroke or TIA treated with clopidogrel" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: 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 PURPOSE To establish the typical error ( TE ) associated with equipment , testing , and biological variation of a running economy ( RE ) test in 11 elite male distance runners ( VO2max 70.3 + /- 7.3 mL x min(-1 ) x kg(-1 ) ) , and measure the between-athlete variation of 70 highly trained runners ( VO2max 69.7 + /- 6.0 mL x min(-1 ) x kg(-1 ) ) to determine the magnitude of the smallest worthwhile change ( SWC ) required for RE . METHODS Runners performed three 4-min bouts of submaximal treadmill running at speeds of 14 , 16 , and 18 km x h(-1 ) ( 0 % grade ) , on two separate occasions within a 7-d period to determine reliability and once over a 3-yr period to measure the SWC . During all RE tests O2 consumption ( VO2 ) , ventilation ( VE ) , respiratory exchange ratio ( RER ) , heart rate ( HR ) , stride rate ( SR ) , and concentration of blood lactate ( Lac ) were determined . RESULTS The TE for the pooled data of three running speeds ( 14 , 16 , and 18 km x h(-1 ) ) was 2.4 % for VO2 , 7.3 % for VE , 27 % for Lac , and ranged between 1 and 4 % for RER , HR , and SR . CONCLUSIONS The results demonstrate that although the magnitude of the TE for a submaximal treadmill running protocol of three 4-min work efforts is small ( 2.4 - 7.3 % ) for measures associated with cardiorespiratory parameters , it is three- to fourfold higher for Lac . Given the small TE associated with RE , and a SWC of similar magnitude for this cohort of distance runners , the RE test is useful in detecting changes attributable to training interventions . Changes in RE greater than approximately 2.4 % in this cohort of elite distance runners are likely to be \" real \" and \" worthwhile , \" and not simply related to testing error and typical variation We investigated the differences in performance between 100-m sprints performed on a sprint treadmill recently vali date d versus on a st and ard track . To date , studies comparing overground and treadmill running have mainly focused on constant and not maximal “ free ” running speed , and compared running kinetics and kinematics over a limited number of steps , but not overall sprint performance . Eleven male physical education students including two sprinters performed one 100-m on the treadmill and one on a st and ard athletics track in a r and omized order , separated by 30 min . Performance data were derived in both cases from speed – time relationships measured with a radar and with the instrumented sprint treadmill , which allowed subjects to run and produce speed “ freely ” , i.e. with no predetermined belt speed imposed . Field and treadmill typical speed – distance curves and data of maximal and mean speed , 100-m time and acceleration/deceleration time constants were compared using t tests and field – treadmill correlations were tested . All the performance parameters but time to reach top speed and deceleration time constant differed significantly , by about 20 % on average , between field and treadmill ( e.g. top speed of 8.84 ± 0.51 vs. 6.90 ± 0.39 m s−1 ) . However , significant correlations were found ( r > 0.63 ; P < 0.05 ) for all the performance parameters except time to reach top speed . Treadmill and field 100-m sprint performances are different , despite the fact that subjects could freely accelerate the belt . However , the significant correlations found make it possible to investigate and interpret inter-individual differences in field performance from treadmill measurements Abstract . Modern ergometric equipment enables the simulation of laboratory maximal oxygen uptake ( V˙O2max ) testing in the field . Therefore , it was investigated whether the improved event specificity on the track might lead to higher V˙O2max measurements in running . Identical protocol s were used on the treadmill and on the track ( speed was indicated by a computer-driven flashing light system ) . Ambulatory measurements of gas exchange were carried out throughout both tests , which were executed in r and omized order . There were no significant differences ( P=0.71 ) in V˙O2max between treadmill [ 4.65 ( 0.51 ) ml·min–1 ] and field tests [ 4.63 ( 0.55 ) ml·min–1 ] . However , the test duration differed significantly ( P<0.001 ) by approximately 5 % : treadmill 691 ( 39 ) s ; field test 727 ( 42 ) s. With the exception of maximum heart rate ( HRmax ; significantly higher in the field with P=0.02 ) all criteria for the degree of effort were similar between the two tests . However , the difference in HRmax at less than 2 beats·min–1 , was practically negligible . Submaximal measurements of oxygen uptake and minute ventilation were significantly higher on the treadmill ( P<0.001 for both parameters ) . In summary , field tests with incremental running protocol s do not result in higher V˙O2max measurements compared to laboratory treadmill exercise . A better running economy on the track results in higher maximal velocities and longer exercise duration s being sustained . The determination of V˙O2max is not a reasonable application for ambulatory gas exchange measurements because laboratory values are not surpassed Abstract Outdoor exercise setting s promote greater psychological well-being than synthetic equivalents , although the influence of the exercise context has not been investigated at high exercise intensities . This study compared the psychological effects of high-intensity exercise in outdoor green and indoor gym setting s in 22 adult runners using a r and omized repeated measures design . Affect and perceived exertion were assessed before , during , and after a 6000-m run with the second half completed at maximum effort . Perceived exertion and activation increased in a progressive manner from baseline to 6000 m , and decreased during the 10-min recovery post-run . Non-significant reductions in affective valence were observed between 3000 and 6000 m , followed by a significant increase post-run . Outcomes did not differ at any time point between the setting s. This study suggested that regular runners experience positive affective responses during and after high-intensity exercise in both a natural outdoor environment and an indoor gym Abstract This study aim ed to test the validity of a non-motorised treadmill ( NMT ) for the measurement of self-paced overground endurance running performance . Ten male runners performed r and omised 5-km running time trials on a NMT and an outdoor athletics track . A range of physiological and perceptual responses was measured , and foot strike was classified subjectively . Performance time was strongly correlated ( r = 0.82 , ICC = 0.86 ) between running modes , despite running time being significantly longer on the NMT ( 1264 ± 124 s vs. 1536 ± 130 s for overground and NMT , respectively ; P < 0.001 ) . End blood lactate concentration and rating of perceived exertion were significantly higher on the NMT compared to overground . Integrated electromyography was significantly lower on the NMT for three muscles ( P < 0.05 ) , and mean stride rate was also significantly lower on the NMT ( P = 0.04 ) . Cardiorespiratory responses of heart rate , oxygen uptake and expired air volume demonstrated strong correlations ( r = 0.68–0.96 , ICC = 0.75–0.97 ) and no statistical differences ( P > 0.05 ) . Runners were consistently slower on the NMT , and as such it should not be used to measure performance over a specific distance . However , the strong correlations suggest that superior overground performance was reflected in relative terms on the NMT , and therefore , it is a valid tool for the assessment of endurance running performance in the laboratory The aim of this study was to compare the physiological responses during 15 min of intermittent running consisting of 30 s of high-intensity running exercise at maximal aerobic velocity ( MAV ) interspersed with 30 s of passive recovery ( 30 - 30 ) performed outdoor versus on a motorized treadmill . Fifteen collegiate physically active males ( age , 22 ± 1 years old ; body mass , 66 ± 7 kg ; stature , 176 ± 06 cm ; weekly training volume , 5 ± 2 h·week-1 ) , performed the Fitness Intermittent Test 45 - 15 to determine maximal oxygen uptake ( V̇O2max ) and MAV and then completed in r and om order 3 different training sessions consisting of a 30-s run/30-s rest on an outdoor athletic track ( 30 - 30 Track ) at MAV ; a 30-s run/30-s rest on a treadmill ( 30 - 30 Treadmill ) at MAV ; a 30-s run/30-s rest at MAV+15 % ( 30 - 30 + 15 % MAV Treadmill ) . Oxygen uptake ( V̇O2 ) , time above 90%V̇O2max ( t90%V̇O2max ) , and rating of perceived exertion ( RPE ) were measured during each training session . We observed a statistical significant underestimation of V̇O2 ( 53.1 ± 5.4 mL·kg-1·min-1 vs 49.8 ± 6.7 mL·kg-1·min-1 , -6.3 % , P = 0.012 ) , t90%V̇O2max ( 8.6 % ± 11.5 % vs 38.7 % ± 32.5 % , -77.8 % , P = 0.008 ) , RPE ( 11.4 ± 1.4 vs 16.5 ± 1.7 , -31 % , P < 0.0001 ) during the 30 - 30 Treadmill compared with the same training session performed on track . No statistical differences between 30 - 30 + 15 % MAV Treadmill and 30 - 30 Track were observed . The present study demonstrates that a 15 % increase in running velocity during a high-intensity intermittent treadmill training session is the optimal solution to reach the same physiological responses than an outdoor training session Abstract Heesch , MWS and Slivka , DR . Running performance , pace strategy , and thermoregulation differ between a treadmill and indoor track . J Strength Cond Res 29(2 ) : 330–335 , 2015—Self-paced time trials have long been used as an indicator of running performance . The purpose of this study was to examine if potential physiological and thermoregulatory differences between treadmill and track running would alter performance in a self-paced 10-km time trial . Ten ( n = 10 ) recreationally trained male distance runners ( age : 32 ± 6 years , height : 177 ± 6 cm , body mass : 76 ± 11 kg , % body fat : 14.4 ± 4.5 , : 62.2 ± 9.5 ml·kg−1·min−1 ) completed two 10-km time trials in a r and omized , counterbalanced order on separate days : 1 on a treadmill at 1 % grade ( TM ) , and 1 on a 200-m indoor track ( IT ) . Core temperature , skin temperature , and heart rate ( HR ) were continuously monitored during the run . The ten-kilometer run time was longer during the IT trial ( 41.66 ± 5.86 minutes ) than during the TM trial ( 40.10 ± 6.06 minutes ; p < 0.001 ) , despite a faster first kilometer in the IT trial ( p = 0.029 ) . There were no differences between TM and IT trials in the HR ( 174 ± 13 b·min−1 and 178 ± 13 b·min−1 , respectively ; p = 0.846 ) or body core temperature ( 38.6 ± 0.5 ° C and 38.9 ± 0.5 ° C , respectively , p = 0.218 ) . Skin temperature was higher in the TM trial ( 35.1 ± 2.5 ° C ) than in the IT trial ( 32.7 ± 3.0 ° C ; p = 0.002 ) . These data indicate that performance differences exist between a 10-km time trial performed on a TM vs. an IT , potentially because of differences in pacing strategy or metabolic cost between the 2 conditions \n Output:\n " }, { "from": "agent", "value": "HR and RPE during motorised treadmill running were higher at faster submaximal speeds and lower at slower submaximal speeds than during overground running .\nConclusions Some , but not all , variables differ between treadmill and overground running , and may be dependent on the running speed at which they are assessed ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: BACKGROUND Hypertension is a common toxicity of bevacizumab , but the frequency of assessment of blood pressure and st and ardized grading remain to be defined . This study aim ed to describe the incidence of bevacizumab-induced hypertension and factors associated with its development , then to retrospectively assess its relation with activity . PATIENTS AND METHODS One hundred nineteen patients with advanced or metastatic non-small cell lung cancer , colorectal cancer , or ovarian cancer receiving bevacizumab ( 2.5 mg/kg per week ) and chemotherapy were eligible for this analysis . Blood pressure was measured at home twice daily according to international guidelines , and grade d according to the National Cancer Institute Common Toxicity Criteria ( NCI-CTC ) , version 3.0 , and the European Society of Hypertension ( ESH ) criteria . RESULTS Home-based measurements detected significantly more cases of hypertension than in-clinic measurements did , according to the ESH criteria ( 54.6 % versus 24.4 % ; p < .001 ) or the NCI-CTC ( 42.9 % versus 22.7 % ; p = .0015 ) . Very early hypertension ( within 42 days , according to the ESH criteria ) but not hypertension ( occurring at any time during treatment period ) was predictive of response ( p = .0011 and p = .26 , respectively ) . CONCLUSIONS Our preliminary results indicate that home-based measurement and grading according to the ESH criteria represents a reliable method to detect bevacizumab-induced hypertension . Whether hypertension is a biomarker of bevacizumab activity remains to be determined in a prospect i ve study OBJECTIVE We examined the safety and efficacy of combining bevacizumab with albumin-bound ( ab- ) paclitaxel to treat patients with recurrent , platinum-resistant primary epithelial ovarian or peritoneal carcinoma . METHODS Patients had measurable disease per RECIST guidelines , progressing within 6 months after a prior course of platinum-based treatment . Patients received ab-paclitaxel 100mg/m(2 ) given by intravenous infusion over 30 min on days 1 , 8 , and 15 of a 28-day cycle with bevacizumab 10mg/kg given on days 1 and 15 . RESULTS Forty-eight patients with an average 1.8 prior lines of treatment participated . The overall response rate was 50 % ( 24/48 ) ( 95 % CI , 34.8 % - 65.1 % ) , with 4 complete and 20 partial responses . Fourteen patients ( 29 % ) had stable disease , whereas eight ( 17 % ) had progressive disease , and two ( 4 % ) were not evaluable . Patients received a median of 6 treatment cycles ( range , 1 - 31 cycles ) . The median progression-free survival was 8.08 months ( 95 % CI , 5.78 - 10.15 months ) ; 6 month progression-free rate was 62.5 % ( 95 % CI , 47.8%-77.2 % ) ; median overall survival was 17.15 months ( 95 % CI , 13.57 - 23.82 months ) . Grade 3 - 4 adverse events included gastrointestinal disorders ( 18.8 % ) , neutropenia ( 8.3 % ) , and hypertension ( 6.3 % ) . CONCLUSIONS Ab-paclitaxel with bevacizumab clearly demonstrates antitumor activity and manageable toxicity profile in patients with recurrent , platinum-resistant ovarian carcinoma . This regimen should be evaluated in a larger r and omized trial BACKGROUND Treatment with cetuximab , a monoclonal antibody directed against the epidermal growth factor receptor , improves overall and progression-free survival and preserves the quality of life in patients with colorectal cancer that has not responded to chemotherapy . The mutation status of the K-ras gene in the tumor may affect the response to cetuximab and have treatment-independent prognostic value . METHODS We analyzed tumor sample s , obtained from 394 of 572 patients ( 68.9 % ) with colorectal cancer who were r and omly assigned to receive cetuximab plus best supportive care or best supportive care alone , to look for activating mutations in exon 2 of the K-ras gene . We assessed whether the mutation status of the K-ras gene was associated with survival in the cetuximab and supportive-care groups . RESULTS Of the tumors evaluated for K-ras mutations , 42.3 % had at least one mutation in exon 2 of the gene . The effectiveness of cetuximab was significantly associated with K-ras mutation status ( P=0.01 and P<0.001 for the interaction of K-ras mutation status with overall survival and progression-free survival , respectively ) . In patients with wild-type K-ras tumors , treatment with cetuximab as compared with supportive care alone significantly improved overall survival ( median , 9.5 vs. 4.8 months ; hazard ratio for death , 0.55 ; 95 % confidence interval [ CI ] , 0.41 to 0.74 ; P<0.001 ) and progression-free survival ( median , 3.7 months vs. 1.9 months ; hazard ratio for progression or death , 0.40 ; 95 % CI , 0.30 to 0.54 ; P<0.001 ) . Among patients with mutated K-ras tumors , there was no significant difference between those who were treated with cetuximab and those who received supportive care alone with respect to overall survival ( hazard ratio , 0.98 ; P=0.89 ) or progression-free survival ( hazard ratio , 0.99 ; P=0.96 ) . In the group of patients receiving best supportive care alone , the mutation status of the K-ras gene was not significantly associated with overall survival ( hazard ratio for death , 1.01 ; P=0.97 ) . CONCLUSIONS Patients with a colorectal tumor bearing mutated K-ras did not benefit from cetuximab , whereas patients with a tumor bearing wild-type K-ras did benefit from cetuximab . The mutation status of the K-ras gene had no influence on survival among patients treated with best supportive care alone . ( Clinical Trials.gov number , NCT00079066 . PURPOSE No biomarkers have been identified to predict outcome with the use of an antiangiogenesis agent for cancer . Vascular endothelial growth factor ( VEGF ) genetic variability has been associated with altered risk of breast cancer and variable promoter activity . Therefore , we evaluated the association of VEGF genotype with efficacy and toxicity in E2100 , a phase III study comparing paclitaxel versus paclitaxel plus bevacizumab as initial chemotherapy for metastatic breast cancer . PATIENTS AND METHODS DNA was extracted from tumor blocks of patients from E2100 . Three hundred sixty-three sample s were available to evaluate associations between genotype and outcome . Genotyping was performed for selected polymorphisms in VEGF and VEGF receptor 2 . Testing for associations between each polymorphism and efficacy and toxicity was performed . RESULTS The VEGF-2578 AA genotype was associated with a superior median overall survival ( OS ) in the combination arm when compared with the alternate genotypes combined ( hazard ratio = 0.58 ; 95 % CI , 0.36 to 0.93 ; P = .023 ) . The VEGF-1154 A allele also demonstrated a superior median OS with an additive effect of each active allele in the combination arm but not the control arm ( hazard ratio = 0.62 ; 95 % CI , 0.46 to 0.83 ; P = .001 ) . Two additional genotypes , VEGF-634 CC and VEGF-1498 TT , were associated with significantly less grade 3 or 4 hypertension in the combination arm when compared with the alternate genotypes combined ( P = .005 and P = .022 , respectively ) . CONCLUSION Our data support an association between VEGF genotype and median OS as well as grade 3 or 4 hypertension when using bevacizumab in metastatic breast cancer \n Output:\n " }, { "from": "agent", "value": "Conclusions Bevacizumab-induced hypertension may represent a prognostic factor in patients with metastatic colorectal cancer" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: AIMS The cardiac resynchronization therapy in heart failure trial ( CARE-HF ) demonstrated that cardiac resynchronization therapy ( CRT ) reduces morbidity and mortality in patients with heart failure and cardiac dyssynchrony . The aim of this study was to develop a prognostic model to evaluate the relationship between prospect ively defined patient characteristics and treatment on the trial primary outcome of death from any cause or unplanned hospitalization for a major cardiovascular event . METHODS AND RESULTS A total of 813 patients were enrolled in the CARE-HF study and were followed for a mean of 29.4 months . A Cox Proportional Hazards Model was fitted to identify predictors of the primary outcome and any predictors that modified the effect of CRT . Ischaemic aetiology , more severe mitral regurgitation and increased N-terminal pro-brain natriuretic peptide , were associated with an increased risk of death or unplanned cardiovascular hospitalization irrespective of cardiac resynchronization [ Hazard ratio ( HR ) 1.89 , 95 % CI 1.45 - 2.46 , HR 1.71 , 95 % CI 1.38 - 2.12 and HR 1.31 , 95 % CI 1.17 - 1.47 , respectively ] and increasing systolic blood pressure with a decreasing risk of an event ( HR 0.99 , 95 % CI 0.98 - 1.00 ) . The benefits of cardiac resynchronization were modified by systolic blood pressure and interventricular mechanical delay ( IVMD ) . Patients with increasing systolic blood pressure appear to receive reduced benefit from CRT ( HR 1.02 , 95 % CI 1.00 - 1.03 ) , whereas those patients with more severe IVMD appear to benefit more from treatment ( HR 0.99 , 95 % CI 0.98 - 1.00 ) . CONCLUSION Patients with echocardiographic evidence of more severe cardiac dyssynchrony and low systolic blood pressure obtain greater benefit from CRT , although benefits were substantial across the range of subjects included in the trial Aims The beneficial effects of CRT in patients with advanced heart failure , wide QRS , and low LVEF have been clearly established . Nevertheless , mortality remains high in some patients . The aims of our study were to identify the predictors of mortality in patients treated with CRT and to design a risk score for mortality . Methods and results A cohort of 608 consecutive patients treated with CRT from 2000 to 2011 in our centre was prospect ively analysed . Baseline clinical and echocardiography variables were analysed and mortality data were collected . During a mean follow-up of 36.2 ± 29.2 months , 174 patients died : 123/174 ( 71 % ) due to cardiovascular causes , 25/174 ( 14 % ) non-cardiac causes , and 26/174 ( 15 % ) unknown aetiology . In a multivariate analysis the predictors of mortality were NYHA class IV [ hazard ratio ( HR ) 2.54 , 95 % confidence interval ( CI ) 1.7–3.7 , P < 0.001 ] , glomerular filtration rate ( GFR ) < 60 mL/min/1.73 m2 ( HR 1.61 , 95 % CI 1.14–2.30 , P = 0.008 ) , AF ( HR 1.67 , 95 % CI 1.19–2.3 , P = 0.01 ) , age ≥70 years ( HR 1.44 , ( 95 % CI 1.04–2.00 , P = 0.02 ) , and LVEF < 22 % ( HR 1.83 , 95 % CI 1.33–2.52 , P ≤ 0.001 ) . The EAARN score ( EF , Age , AF , Renal dysfunction , NYHA class IV ) summarizes the predictors . Each additional predictor increased the mortality : one predictor , HR 3.28 ( 95 % CI 1.37–7.8 , P = 0.008 ) ; two , HR 5.23 ( 95 % CI 2.24–12.10 , P < 0.001 ) ; three , HR 9.63 ( 95 % CI 4.1–22.60 , P < 0.001 ) ; and four or more , HR 14.38 ( 95 % CI 5.8–35.65 , P < 0.001 ) . Conclusion The predictors of mortality have a significant add-on predictive effect on mortality . The EAARN score could be useful to stratify the prognosis of CRT patients OBJECTIVES This study was design ed to examine the use of cardiovascular medications and outcomes in patients with heart failure ( HF ) and renal dysfunction . BACKGROUND Renal insufficiency is associated with poorer outcomes in patients with HF , but the mechanisms are uncertain . In particular , the degree of therapeutic nihilism in these patients , and whether it is appropriate , is unclear . METHODS This was a prospect i ve cohort study with a one-year follow-up . RESULTS In 6,427 patients with cardiologist-diagnosed HF and angiographically proven coronary artery disease ( mean age 69 years ; 65 % men ; one-year mortality , 10 % ) , 39 % had creatinine clearances < 60 ml/min . Patients with renal insufficiency were less likely to be prescribed angiotensin-converting enzyme ( ACE ) inhibitors , beta-blockers , statins , or aspirin ( all p < 0.001 ) . However , users of aspirin ( odds ratio [ OR ] 0.69 , 95 % confidence interval [ CI ] 0.57 to 0.85 ) , statins ( OR 0.79 , 95 % CI 0.64 to 0.97 ) , and beta-blockers ( OR 0.75 , 95 % CI 0.62 to 0.90 ) were less likely to die in the subsequent 12 months than nonusers , irrespective of renal function ( all OR adjusted for covariates including atherosclerotic burden and ejection fraction ) . Although ACE inhibitor users with creatinine clearances > or = 60 ml/min had lower 12-month mortality ( OR 0.72 , 95 % CI 0.48 to 0.99 ) , ACE inhibitor users with clearances < 60 ml/min did not ( OR 1.21 , 95 % CI 0.97 to 1.51 ) . CONCLUSIONS Renal insufficiency is common in patients with HF and coronary artery disease , and these patients have more advanced coronary atherosclerosis . Patients with renal insufficiency are less likely to be prescribed efficacious therapies , but have better outcomes if they receive these medications Background — The factors that determine the risk for sudden death or implantable cardioverter defibrillator therapy in patients receiving cardiac resynchronization therapy ( CRT ) therapies are largely unknown . Methods and Results — We hypothesized that clinical measures of heart failure severity and the presence of comorbid conditions would predict the risk of malignant arrhythmias in the 1520 patients enrolled in the Comparison of Medical Therapy , Pacing , and Defibrillation in Heart Failure ( COMPANION ) Trial . Outcomes in the CRT group after implantable cardioverter defibrillator therapy were also evaluated . The CRT-defibrillator device reduced the risk of sudden death by 56 % compared with drug therapy ( 17 of 595 [ 2.9 % ] versus 18 of 308 [ 5.8 % ] , P<0.02 ) . CRT therapy was not associated with sudden death risk reduction ( 48 of 617 [ 7.8 % ] ) . Other factors associated with reduced sudden death risk were left ventricular ejection fraction > 20 % ( HR , 0.55 [ 95 % CI , 0.35 to 0.87 ] ; P=0.01 ) , QRS duration > 160 ms ( HR , 0.63 [ 95 % CI , 0.40 to 0.997 ] ; P=0.05 ) , and female gender ( HR , 0.56 [ 95 % CI , 0.34 to 0.94 ] ; P=0.003 ) . The risk for sudden death was increased by advanced New York Heart Association class IV heart failure ( HR , 2.62 [ 95 % CI , 1.61 to 4.26 ] ; P<0.011 ) and renal dysfunction ( HR , 1.69 [ 95 % CI , 1.06 to 2.69 ] ; P=0.03 ) . An appropriate shock was experienced in 88 ( 15 % ) of the 595 CTR-D patients . In the CRT-defibrillator patients , female gender ( HR , 0.54 [ 95 % CI , 0.31 to 0.94 ] ; P=0.03 ) and use of neurohormonal antagonists were associated with reduced risk . Class IV heart failure status increased risk . Appropriate implantable cardioverter defibrillator therapy was positively associated with risk of death or all-cause hospitalization ( HR , 1.57 ; P<0.002 ) , pump failure death or hospitalization ( HR , 2.35 ; P<0.001 ) , and sudden death ( HR , 2.99 ; P=0.03 ) , but not total mortality ( HR , 1.3 ; P=0.28 ) . Conclusions — In CRT c and i date s , sudden cardiac death risk is associated with higher New York Heart Association class and renal dysfunction . In CRT-defibrillator recipients , reduction in the risk of an appropriate shock is associated with medical therapy with neurohormonal antagonists , female gender , and New York Heart Association functional class III versus IV clinical status . Shock therapy was associated with worse outcome BACKGROUND Chronic kidney disease ( CKD ) severity is associated with increased morbidity and mortality in congestive heart failure . There is a paucity of data regarding renal improvement after cardiac resynchronization therapy ( CRT ) and its potential impact on clinical outcomes , especially in patients with severe CKD . METHOD This was a retrospective analysis of a prospect ively collected cohort of 260 patients with CKD undergoing CRT at a single center . Renal function was compared before and after CRT . The primary end point was a composite of death , heart transplant , and left ventricular assist device ( LVAD ) , assessed at 5 years . RESULTS Patients with more severe CKD demonstrated increased risk of death , transplant , or LVAD following CRT ( P = 0.015 ) . Renal response ( estimated glomerular filtration rate improvement ≥10 mL/min/1.73 m(2 ) ) was observed in 14 % of all patients and 28 % of patients with stage IV CKD . Independent predictors of renal response included left ventricular ejection fraction improvement ( odds ratio [ OR ] 1.06 , confidence interval [ CI ] 1.01 - 1.10 ) , angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use ( OR 4.31 , CI 1.08 - 17.23 ) , and advanced CKD stage ( OR 2.19 , CI 1.14 - 4.23 ) . Renal response independently decreased hazard of the primary outcome ( HR 0.24 , CI 0.08 - 0.73 , P = 0.01 ) . Renal responders with stage IV CKD had 80 % 5-year event-free survival , compared to 0 % for nonrenal responders in stage IV ( P = 0.03 ) . CONCLUSION Although severity of CKD is associated with poorer outcome after CRT , improvement in renal function can occur in patients across all CKD stages . Renal responders , including those with stage IV CKD , demonstrate favorable 5-year outcomes . Assessment of renal response may help better prognostic outcomes following CRT AIMS The CArdiac REsynchronization-Heart Failure study r and omized patients with left ventricular ejection fraction < or = 35 % , markers of cardiac dyssynchrony , and persistent moderate or severe symptoms of heart failure despite pharmacological therapy , to implantation of a cardiac resynchronization therapy ( CRT ) device or not . The main study observed substantial benefits on morbidity and mortality during a mean follow-up of 29.4 months [ median 29.6 , interquartile range ( IQR ) 23.6 - 34.6 ] . Prior to study closure , an extension phase lasting a further 8 months ( allowing time for data analysis and presentation ) was declared during which cross-over was discouraged . METHODS AND RESULTS This was an extension of the already reported open-label r and omized trial described above . The primary outcome of the extension phase was all-cause mortality from the time of r and omization to completion of the extension phase . The secondary outcome was mode of death . The mean follow-up was 37.4 months ( median 37.6 , IQR 31.5 - 42.5 , range 26.1 - 52.6 months ) . There were 154 deaths ( 38.1 % ) in 404 patients assigned to medical therapy and 101 deaths ( 24.7 % ) in \n Output:\n " }, { "from": "agent", "value": "Baseline renal dysfunction has an adverse effect on-all cause mortality in patients who underwent CRT" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: OBJECTIVE Percutaneous access during endovascular aneurysm repair has been difficult owing to the large size of the delivery catheters . This study reports a single-center experience of totally percutaneous access during endovascular abdominal and thoracic aortic repairs using the Preclose Proglide device ( Abbott Vascular , Redwood City , Calif ) . METHODS Between December 2004 and August 2006 , 262 endovascular aortic aneurysm repairs were performed . Percutaneous access was used for the introduction of 12F to 24F sheaths ( 4.4-mm to 8.6-mm outer diameter ) . The technique involved deployment of two Proglide devices before insertion of the sheath ( \" Preclose \" technique ) with the sutures left extracorporeally for closure after conclusion of the procedure . A prospect ively maintained endovascular data base and medical records were retrospectively review ed . Rates of technical success , failure modes , and the overall duration of the endovascular repair compared with a similar cohort using open femoral exposures were examined . RESULTS A total of 559 Proglide devices were used to close 279 femoral arteries , and 175 ( 63 % ) required the insertion of 18F to 24F sheaths . There were 16 failures , mainly due to obesity , device malfunction , severe calcific disease , and faulty arterial punctures , for a technical success rate of 94.3 % . The success rates for 12F to 16F size sheaths were significantly higher than for the larger 18F to 24F sheaths ( 99.0 % vs 91.4 % , P<.01 ) . For both endovascular abdominal ( EVAR ) and thoracic ( TEVAR ) aortic repairs , the Preclose technique result ed in shorter overall procedure times compared with a similar cohort in which open femoral exposures were used ( EVAR , 115 vs 128 min , P<.001 ; TEVAR , 80 vs 112 , P=.019 ) . Despite this reduction of procedure time , the savings on the cost of operating room time was negated by the cost of the Proglide devices ( $ 295 per device ) . CONCLUSIONS Percutaneous access for endovascular aortic repair is safe and feasible using the Proglide device . Although the success rates are higher for smaller size sheaths , successful closures may be obtained for up to 24F sheaths . Percutaneous access may result in shorter overall procedure times and potentially lower operating room costs , but this appears to be offset by the cost of the closure devices OBJECTIVE The first multicenter r and omized controlled trial was design ed and conducted to assess the safety and effectiveness of totally percutaneous endovascular aortic aneurysm repair ( PEVAR ) with use of a 21F endovascular stent graft system and either an 8 F or 10 F suture-mediated closure system ( the PEVAR trial , NCT01070069 ) . A noninferiority trial design was chosen to compare percutaneous access with st and ard open femoral exposure . METHODS Between 2010 and 2012 , 20 U.S. institutions participated in a prospect i ve , Food and Drug Administration-approved r and omized trial to evaluate percutaneous femoral artery access and closure by a \" preclose \" technique in conjunction with endovascular abdominal aortic aneurysm repair . A total of 151 patients were allocated by a 2:1 design to percutaneous access/closure ( n = 101 ) or open femoral exposure ( n = 50 [ FE ] ) . PEVAR procedures were performed with either the 8 F Perclose ProGlide ( n = 50 [ PG ] ) or the 10 F Prostar XL ( n = 51 [ PS ] ) closure devices . All endovascular abdominal aortic aneurysm repair procedures were performed with the Endologix 21 F profile ( outer diameter ) sheath-based system . Patients were screened by computed tomography with three-dimensional reconstruction and independent physician review for anatomic suitability and adequate femoral artery anatomy for percutaneous access . The primary trial end point ( treatment success ) was defined as procedural technical success and absence of major adverse events and vascular complications at 30 days . An independent access closure sub study evaluated major access-related complications . Clinical utility and procedural outcomes , ankle-brachial index , blood laboratory analyses , and quality of life were also evaluated with continuing follow-up to 6 months . RESULTS Baseline characteristics were similar among groups . Procedural technical success was 94 % ( PG ) , 88 % ( PS ) , and 98 % ( FE ) . One-month primary treatment success was 88 % ( PG ) , 78 % ( PS ) , and 78 % ( FE ) , demonstrating noninferiority vs FE for PG ( P = .004 ) but not for PS ( P = .102 ) . Failure rates in the access closure sub study analyses demonstrated noninferiority of PG ( 6 % ; P = .005 ) , but not of PS ( 12 % ; P = .100 ) , vs FE ( 10 % ) . Compared with FE , PG and PS yielded significantly shorter times to hemostasis and procedure completion and favorable trends in blood loss , groin pain , and overall quality of life . Initial noninferiority test results persist to 6 months , and no aneurysm rupture , conversion to open repair , device migration , or stent graft occlusion occurred . CONCLUSIONS Among trained operators , PEVAR with an adjunctive preclose technique using the ProGlide closure device is safe and effective , with minimal access-related complications , and it is noninferior to st and ard open femoral exposure . Training , experience , and careful application of the preclose technique are of paramount importance in ensuring successful , sustainable outcomes BACKGROUND Although endovascular aneurysm repair ( EVAR ) has a lower 30-day operative mortality than open repair , the long-term results of EVAR are uncertain . We instigated EVAR trial 1 to compare these two treatments in terms of mortality , durability , health-related quality of life ( HRQL ) , and costs for patients with large abdominal aortic aneurysm ( AAA ) . METHODS We did a r and omised controlled trial of 1082 patients aged 60 years or older who had aneurysms of at least 5.5 cm in diameter and who had been referred to one of 34 hospitals proficient in the EVAR technique . We assigned patients who were anatomically suitable for EVAR and fit for an open repair to EVAR ( n=543 ) or open repair ( n=539 ) . Our primary endpoint was all-cause mortality , with secondary endpoints of aneurysm related mortality , HRQL , postoperative complications , and hospital costs . Analyses were by intention to treat . FINDINGS 94 % ( 1017 of 1082 ) of patients complied with their allocated treatment and 209 died by the end of follow-up on Dec 31 , 2004 ( 53 of aneurysm-related causes ) . 4 years after r and omisation , all-cause mortality was similar in the two groups ( about 28 % ; hazard ratio 0.90 , 95 % CI 0.69 - 1.18 , p=0.46 ) , although there was a persistent reduction in aneurysm-related deaths in the EVAR group ( 4%vs 7 % ; 0.55 , 0.31 - 0.96 , p=0.04 ) . The proportion of patients with postoperative complications within 4 years of r and omisation was 41 % in the EVAR group and 9 % in the open repair group ( 4.9 , 3.5 - 6.8 , p<0.0001 ) . After 12 months there was negligible difference in HRQL between the two groups . The mean hospital costs per patient up to 4 years were UK pound sterling 13,257 for the EVAR group versus pound sterling 9946 for the open repair group ( mean difference pound sterling 3311 , SE 690 ) . INTERPRETATION Compared with open repair , EVAR offers no advantage with respect to all-cause mortality and HRQL , is more expensive , and leads to a greater number of complications and re interventions . However , it does result in a 3 % better aneurysm-related survival . The continuing need for interventions m and ates ongoing surveillance and longer follow-up of EVAR for detailed cost-effectiveness assessment PURPOSE To evaluate safety and cost benefits of the percutaneous technique for treatment of aortic aneurysm , a prospect i ve r and omized study was performed that compared the endovascular suture technique with conventional cutdown access and repair . MATERIAL S AND METHODS From January 2002 through July 2002 , 30 endografts , including 14 Talent stent-grafts ( Medtronic , Sunrise , Fla ) and 16 Zenith endografts ( Cook , Bloomington , Ind ) were implanted in 30 patients for endovascular aneurysm treatment . The patients were r and omized to either percutaneous technique ( group A ) or conventional cutdown ( group B ) . Fifty-five femoral arteries were cannulated with large-bore ( 14F-25F ) introducers and were included in the study . Safety and efficiency of both techniques were assessed by recording the complication rates , operation time , discharge , and time to ambulation . Comparison of selected estimated costs included both variable and fixed costs for femoral access and expenses for treatment of complications . RESULTS No operative deaths occurred . The complication rates were similar and included 1 arterial thrombosis in each group , 3 lymphoceles in group B , and 1 conversion to cutdown because of bleeding in group A. Mean surgery time ( 86.7 + /- 27 minutes vs 107.8 + /- 38.5 minutes ; P < .05 ) and time to ambulation ( 20.1 + /- 4.3 hours vs 33.1 + /- 18.4 hours ; P < .001 ) were significantly shorter in the group treated percutaneously . Because of the cost of the closure device , total cost of the percutaneous technique averaged 99.2 euro ; more than cutdown . CONCLUSIONS The percutaneous technique decreases the invasiveness of endovascular therapy of aortic aneurysm and reduces operative time and time to ambulation . Complications were roughly equivalent in severity . The additional cost for the device appears to justify its use for this form of aneurysm treatment PURPOSE This study was design ed to describe and evaluate our preliminary results with a percutaneous arterial closure device as compared to those obtained with conventional femoral surgical cut down during endovascular repair of abdominal aortic aneurysms ( AAA ) . MATERIAL AND METHODS Between January 2004 and December 2006 , 40 of 86 AAA patients selected for endovascular repair met the criteria for inclusion in this study . Nineteen of these patients ( Group A ) received a bifurcated endograft placed by direct puncture of the femoral arteries ( 38 femoral triangles ) with closure by a Prostar((R ) ) percutaneous arterial closure device ( Abbott ) . The other 21 patients ( control group B ) were managed with a bifurcated endograft placed by conventional open surgery ( 42 femoral triangles ) . Data concerning all 40 patients were collected prospect ively and analyzed . RESULTS The technical success rate was 92 % ( group A ) vs 90 % ( group B ) , P=0.79 . The incidence of perioperative complications was 16 % ( 3/19 ) in group A and 14 % ( 3/21 ) in group B ( P=0.89 ) . The mean hospital stay was 5.8 days in group A and 7.8 days in group B ( P=0.05 ) . The difference in the length of hospitalisation was associated with reduced cost for the percutaneous group ( 5579.60 euros vs. 7503.60 euros ; P=0.04 ) , that counterbalanced the cost induced by the Prostar XL((R ) ) suture mediated device . Mean follow-up in both groups was 12 months . The overall incidence of locoregional complications after one year of follow-up was 11 % ( 2/19 ) in group A and 19 % ( 4/21 ) in group B ( P=0.45 ) . CONCLUSION This study confirms the feasibility and safety of total percutaneous endovascular AAA repair . Our preliminary results suggest that the costs paid by healthcare providers for endovascular AAA repair might not be increased with the selective use of percutaneous closure devices Endovascular exclusion of abdominal aortic aneurysms ( AAAs ) was developed in an effort to treat patients who were at high risk for complications following st and ard surgical repair . Stent grafts used for endovascular repair of AAAs require the use of large‐bore sheaths and surgical exposure of the common femoral arteries ( CFAs ) . To decrease the invasiveness of AAA repair , we attempted to perform the procedure percutaneously utilizing the Prostar XL Percutaneous Vascular Surgery Device and the preclose technique . Thirty patients underwent an attempted percutaneous AAA repair . These patients were followed prospect ively to assess the success of the procedure . Twenty‐eight patients ( 93 % ) had successful percutaneous repair of both CFA access sites . One patient had inadequate hemostasis of the 22 Fr CFA entry site and one patient had inadequate hemostasis of the 16 Fr CFA entry site . Both of these CFA sites underwent open \n Output:\n " }, { "from": "agent", "value": "Conclusion : PEVAR had a similar technical success rate , shorter procedure time , and lower complication rate compared with OFA .\nThus , percutaneous access appears to be the preferential approach for EVAR ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: To study the efficacy of an injury prevention program in a r and omized trial , 12 teams ( 180 players ) in a male senior soccer division were followed up for 6 months . The 12 teams were allocated at r and om to two groups of six teams , one being given a prophylactic program and the other serving as control . The program was based on previous studies of injury mechanisms . It comprised ( 1 ) correction of training , ( 2 ) provision of optimum equipment ; ( 3 ) prophylactic ankle taping ; ( 4 ) controlled rehabilitation ; ( 5 ) exclusion of players with grave knee instability ; ( 6 ) information about the impor tance of disciplined play and the increased risk of injury at training camps ; and ( 7 ) correction and supervision by doctor(s ) and physiotherapist(s ) . The injuries in the test teams were 75 % fewer than in the controls . The most common types of soccer injuries , sprains and strains to ankles and knees , were all significantly reduced . It is concluded that the pro posed prophylactic program , including close supervi sion and correction by doctors and physiotherapists , significantly reduces soccer injuries BACKGROUND AND PURPOSE The purpose s of this study were ( 1 ) to examine the effects of a passive hip extension stretching exercise program on hip extension range of motion ( ROM ) , ( 2 ) to examine the effects of a trunk flexor exercise program on trunk flexor muscle performance , and ( 3 ) to examine the effects of passive hip extension stretching or trunk flexor exercises on walking and running economy . ( \" Gait economy \" is defined as the steady-state oxygen consumption per unit of body weight required to walk or run at a specified velocity . ) SUBJECTS Twenty-five healthy , athletic , male college students ( mean age = 21 years , mean weight = 75 kg , mean height = 172 cm ) were r and omly assigned to one of three groups : a control group ( n = 7 ) , a hip extension stretching group ( n = 9 ) , or a trunk flexor exercise group ( n = 9 ) . METHODS Before and after 3 weeks of intervention , the following measurements were obtained : right and left hip extension ROM , trunk flexor muscle performance , and walking and running economy . A three x two-way ( groups x test sessions ) analysis of variance ( ANOVA ) for repeated measures for unequal subject numbers was performed on each of the five dependent measures , with analysis of simple main effects applied when significant interactions were found . RESULTS The ANOVA on right and left hip extension ROM revealed a significant interaction . Analyses of simple main effects showed that 3 weeks ( six sessions ) of passive hip extension stretching significantly improved right hip extension ROM ( pretest = -20.4 degrees , posttest = -8.3 degrees ) and left hip extension ROM ( pretest = -16.8 degrees , posttest = -7.0 degrees ) . There also was a significant interaction for trunk flexor muscle performance . The analysis of simple main effects revealed that 3 weeks of daily trunk flexor exercises significantly improved trunk flexor muscle performance ( pretest = 41.5 degrees , posttest = 60.4 degrees ) . The 3-week intervention program of hip extension stretching or trunk flexion exercises , however , did not produce significant changes in walking or running economy . CONCLUSION AND DISCUSSION The results suggest that ( 1 ) six treatment sessions of passive stretching were sufficient to improve hip extension ROM ; ( 2 ) 3 weeks of exercises performed daily improved trunk flexor muscle performance ; and ( 3 ) training of isolated tasks , such as hip flexibility or trunk strengthening activities , did not produce the desired outcome in the economy of walking or running . Possible reasons for the results are discussed OBJECTIVE Increased muscle flexibility from static stretching is supported by the literature , but limited research has assessed the duration of maintained flexibility gains in knee joint range of motion after same-day static hamstring stretching . The purpose of our study was to determine the duration of hamstring flexibility gains , as measured by an active knee-extension test , after cessation of an acute static stretching protocol . DESIGN AND SETTING All subjects performed 6 active warm-up knee extensions , with the last repetition serving as the baseline comparison measurement . After warm-up , the experimental group performed 4 30-second static stretches separated by 15-second rests . SUBJECTS Thirty male subjects ( age = 19.8 + /- 5.1 years , ht = 179.4 + /- 18.7 cm , wt = 78.5 + /- 26.9 kg ) with limited hamstring flexibility of the right lower extremity were r and omly assigned to control and experimental groups . MEASUREMENTS Postexercise active knee-extension measurements for both groups were recorded at 1 , 3 , 6 , 9 , 15 , and 30 minutes . RESULTS Tukey post hoc analysis indicated significant improvement of knee-extension range of motion in the experimental group that lasted 3 minutes after cessation of the static stretching protocol . Subsequent measurements after 3 minutes were not statistically different from baseline . A dependent t test revealed a significant increase in knee-extension range of motion when comparing the first to the sixth active warm-up repetition . CONCLUSIONS Our results suggest that 4 consecutive 30-second static stretches enhanced hamstring flexibility ( as determined by increased knee-extension range of motion ) , but this effect lasted only 3 minutes after cessation of the stretching protocol . Future research should examine the effect of other stretching techniques in maintaining same-day flexibility gains Two-hundred and ninety-four male and 224 female r and omly selected recreational cyclists responded to a mail question naire . Significant differences were observed between male and female cyclists ' training characteristics . Overall , 85 % of the cyclists reported one or more overuse injury , with 36 % requiring medical treatment . The most common anatomical sites for overuse injury/complaints reported by the male and female cyclists combined were the neck ( 48.8 % ) , followed by the knees ( 41.7 % ) , groin/buttocks ( 36.1 % ) , h and s ( 31.1 % ) , and back ( 30.3 % ) . For the male cyclists , effect upon back and groin/buttocks overuse injuries/complaints were miles/week , lower number of gears , and less years of cycling . For female cyclists , training characteristics which had the most significant effect upon groin/buttocks overuse injury/complaints were more non-competitive events/year and less stretching before cycling . The odds of female cyclists developing neck and shoulder overuse injury/complaints were 1.5 and 2.0 times more , respectively than their male counterparts Young female players in European h and ball have a very high injury incidence , up to 50 injuries per 1000 hours of game . More than half of these injuries happen without any external cause . The aim of the study was to investigate the effect of an intervention programme design ed to reduce the number of injuries in young female players in European h and ball , with special emphasis on injuries in the lower extremities . The programme was created using elite athlete training programmes and those design ed for rehabilitation of injured athletes with functional instability of their ankles and rupture of the anterior cruciate ligament . It included the use of an ankle disk for 10 - 15 min at all practice sessions , for one 10-month season ( August 1995-May 1996 ) . Twenty-two teams participated in the study , and were r and omly assigned to the intervention or control group . Eleven teams with 111 players were r and omised to the intervention group and 11 teams with 126 players to the control group . Data were analysed using a t-test for continuous variables , chi2- analysis and Fisher 's exact test for dichotomous variables and multivariate methods to determine odds-ratios . The results indicated that using the intervention programme decreased the numbers of both traumatic and overuse injuries significantly . The differences in injuries between the groups were 80 % during games and 71 % during practice . In addition , the players in the control group had a 5.9 times higher risk of acquiring an injury than the players in the intervention group Forty-seven male subjects were r and omly assigned to 4 different groups . Three groups of 10 subjects trained three times a week with a modified contract-relax ( CR ) method for improving muscle flexibility . Seventeen sub jects trained during the same time with a traditional ballistic stretch ( BS ) method . After 30 days ( 14 training sessions ) the latter group switched over to the CR method . The results showed that the CR method was significantly better than the BS method for improving muscle flexibility in the four different , bilateral muscle groups studied . After the initial 30 days the three groups of 10 subjects trained one , three , and five times a week , respectively , for another 30 days . The results showed that once a week was enough to maintain improved flexibility , while three and five times a week increased it further . The former BS group improved muscle flexibility between the 30th and 60th day , as expected from the results of the initial 30 days with the three CR groups , when training with the CR method three times a week To prospect ively evaluate the effect of neuromuscular training on the incidence of knee injury in female athletes , we monitored two groups of female athletes , one trained before sports participation and the other not trained , and a group of untrained male athletes throughout the high school soccer , volleyball , and basketball seasons . Weekly reports included the number of practice and competition exposures and mechanism of injury . There were 14 serious knee injuries in the 1263 athletes tracked through the study . Ten of 463 untrained female athletes sustained serious knee injuries ( 8 noncontact ) , 2 of 366 trained female athletes sustained serious knee injuries ( 0 noncontact ) , and 2 of 434 male athletes sustained serious knee injuries ( 1 noncontact ) . The knee injury incidence per 1000 athlete-exposures was 0.43 in untrained female athletes , 0.12 in trained female athletes , and 0.09 in male athletes ( P 0.02 , chi-square analysis ) . Untrained female athletes had a 3.6 times higher incidence of knee injury than trained female athletes ( P 0.05 ) and 4.8 times higher than male athletes ( P 0.03 ) . The incidence of knee injury in trained female athletes was not significantly different from that in untrained male athletes ( P 0.86 ) . The difference in the incidence of noncontact injuries between the female groups was also significant ( P 0.01 ) . This prospect i ve study demonstrated a decreased incidence of knee injury in female athletes after a specific plyometric training program The effect of a combination of a warm-up , stretching exercises and massage on subjective scores for delayed onset muscle soreness ( DOMS ) and objective functional and biochemical measures was studied . Fifty people , r and omly divided in a treatment and a control group , performed eccentric exercise with the forearm flexors for 30 min . The treatment group additionally performed a warm-up and underwent a stretching protocol before the eccentric exercise and massage afterwards . Functional and biochemical measures were obtained before , and 1 , 24 , 48 , 72 and 96h after exercise . The median values at the five post-exercise time points differed significantly for DOMS measured when the arm was extended ( p = 0.043 ) . Significant main effects for treatment were found on the maximal force ( p = 0.026 ) , the flexion angle of the elbow ( p = 0.014 ) and the creatine kinase activity in blood ( p = 0.006 ) . No time-by-treatment interactions were found . DOMS on pressure , extension angle and myoglobin concentration in blood did not differ between the groups . This combination of a warm-up , stretching and massage reduces some negative effects of eccentric exercise , but the results are inconsistent , since some parameters were significantly affected by the treatment whereas others were not , despite the expected efficacy of a combination of treatments . The objective measures did not yield more unequivocal results than the subjective DOMS scores Research demonstrates an inverse relationship between the range of motion of selected joint movements ( flexibility ) and running economy . Since stretching exercises have been shown to increase joint range of motion , stretching exercises may be contraindicated for endurance running performance . Hence , this study investigated the influence of a 10-week program of stretching exercises on the oxygen costs of a 10 min sub-maximal ( approx . 70 % peak VO(2 ) ) treadmill run . Thirty-two ( 16 female , 16 male ) physically active , treadmill accommo date d , college students participated in the study . All participants maintained their current activity level , with half the participants ( 8 female , 8 male ) adding a 40 min , 3 days per week session of thigh and calf muscle stretching exercises . After 10 weeks , the stretching group ( STR ) exhibited a significant ( P<0.05 ) increase ( 3.1+/-2.2 cm ) in the sit- and -reach , while the non-stretching group ( CON ) experienced no significant ( P>0.05 ) change ( 0.0+/-0.4 cm ) . However , neither the STR nor the CON exhibited a significant ( P>0.05 ) change in the O(2 ) cost for the submaximal run . It is concluded , therefore , that a chronic stretching program does not necessarily negatively influence running economy Hamstring muscle strain represents a significant injury to the athlete participating in sporting activities . Lack of hamstring flexibility has been correlated to hamstring muscle injury . There is , however , conflict concerning the most efficient hamstring stretching technique . The purpose of this study was to compare static stretch ( SS ) and proprioceptive neuromuscular facilitation ( PNF ) hamstring stretching techniques while maintaining the pelvis in two testing positions : anterior pelvic tilt ( APT ) or posterior pelvic tilt ( PPT ) . Two groups of 10 subjects were r and omly assigned to either an APT or PPT position . Each subject then performed eight sessions using PNF \n Output:\n " }, { "from": "agent", "value": "There is not sufficient evidence to endorse or discontinue routine stretching before or after exercise to prevent injury among competitive or recreational athletes ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: BACKGROUND Childhood risk factors for the development of adult schizophrenia have proved to have only modest and nonspecific effects , and most seem unrelated to the adult phenotype . We report the first direct examination of the longitudinal relationship between psychotic symptoms in childhood and adulthood . METHODS We analyzed prospect i ve data from a birth cohort ( N = 761 ) , in which children were asked about delusional beliefs and hallucinatory experiences at age 11 years , and then followed up to age 26 years . Structured diagnostic interviews were employed at both ages and self-report of schizophreniform symptoms was augmented by other data sources at age 26 years . RESULTS Self-reported psychotic symptoms at age 11 years predicted a very high risk of a schizophreniform diagnosis at age 26 years ( odds ratio , 16.4 ; 95 % confidence interval , 3.9 - 67.8 ) . In terms of attributable risk , 42 % of the age-26 schizophreniform cases in the cohort had reported 1 or more psychotic symptoms at age 11 years . Age-11 psychotic symptoms did not predict mania or depression at age 26 years , suggesting specificity of prediction to schizophreniform disorder . The link between child and adult psychotic symptoms was not simply the result of general childhood psychopathology . CONCLUSION These findings provide the first evidence for continuity of psychotic symptoms from childhood to adulthood BACKGROUND In the UK and The Netherl and s , people with high rates of psychosis are chronically exposed to discrimination . AIMS To test whether perceived discrimination is associated longitudinally with onset of psychosis . METHOD A 3-year prospect i ve study of cohorts with no history of psychosis and differential rates of reported discrimination on the basis of age , gender , disability , appearance , skin colour or ethnicity and sexual orientation was conducted in the Dutch general population ( n=4076 ) . The main outcome was onset of psychotic symptoms ( delusions and hallucinations ) . RESULTS The rate of delusional ideation was 0.5 % ( n=19 ) in those who did not report discrimination , 0.9 % ( n=4 ) in those who reported discrimination in one domain , and 2.7 % ( n=3 ) in those who reported discrimination in more than one domain ( exact P=0.027 ) . This association remained after adjustment for possible confounders . No association was found between baseline discrimination and onset of hallucinatory experiences . CONCLUSIONS Perceived discrimination may induce delusional ideation and thus contribute to the high observed rates of psychotic disorder in exposed minority population OBJECTIVES Previous research into schizotypy has shown that certain groups of people have similar experiences to the positive symptoms of schizophrenia but remain functioning members of society , such as those with profound religious experiences ( Jackson & Fulford , 1997 ) . METHOD The focus of the present study was to explore the incidence of delusional ideation in New Religious Movements ( NRMs ) . Hare Krishnas and Druids were compared to two control groups ( non-religious and Christian ) , and to deluded , psychotic in- patients on two delusions measures . RESULTS As predicted , individuals from the NRMs scored significantly higher than the control groups on all the delusional measures apart from levels of distress . They did not show as much florid symptomatology as the psychotic patients , but could not be differentiated from the deluded group on the number of delusional items endorsed on the Peters et al. Delusions Inventory ( PDI ; Peters , Day & Garety , 1996 ) , or on levels of conviction . However , they were significantly less distressed and preoccupied by their experiences . No differences were found between the two control groups on any of the delusional measures , suggesting that religious beliefs per se do not account for the NRMs members ' scores . DISCUSSION These findings provide further support for , first , the notion of a continuum between normality and psychosis and , second , for the necessity to consider the multidimensionality of delusional beliefs In traditional Western psychiatric theory , seeing or hearing things that other people do not think are there could be termed a hallucination which is often considered indicative of underlying psychopathology . The psychiatric interpretation of pathological meanings of these experiences for an individual can be contrasted with an anthropologic approach which considers whether there are underlying cultural influences to account for certain distributions of reported hallucinations and their content and to ask about the social and spiritual , as well as psychologic , meanings of such experiences . This paper presents data on reported hallucinations in a r and om sample of the general population of a county in north central Florida . When the results of the questions on hallucinations were compared in relation to sociodemographic variables , it was found that hallucinations were more commonly reported by the young , by blacks , by members of the lower socioeconomic quintiles and by those belonging to certain church types . These data will be discussed from the complementing and contrasting psychiatric and anthropologic viewpoints College undergraduates ( n = 34 ) identified by deviant scores ( at least 1.96 SD above the mean ) on the Revised Social Anhedonia ( SocAnh ) Scale ( M. Eckblad , L. J. Chapman , J. P. Chapman , & M. Mishlove , 1982 ) were compared with control participants ( n = 139 ) at an initial assessment and at a 10-year follow-up evaluation . Twenty-four percent of the SocAnh group were diagnosed with schizophrenia-spectrum disorders at the follow-up compared with only 1 % of the control group , despite the fact that there had been no such difference between the groups at the initial assessment 10 years earlier . The SocAnh group exceeded the control group on severity of psychotic-like experiences and had poorer overall adjustment at the follow-up but not at the initial assessment . The groups did not differ on mood symptoms or substance-use disorders . Thus , the SocAnh Scale , unlike the Perceptual Aberration and Magical Ideation Scales , appears to identify individuals at specific risk for future development of schizophrenia-spectrum disorders OBJECTIVE Reports of increased rates of psychosis in prisons could be due to sampling and ascertainment differences . The authors compared two sample s of subjects 16 - 64 years of age : those from the general population of residents in Great Britain and prisoners in Engl and and Wales . METHOD A r and om sample of rem and ed and sentenced male and female prisoners ( N=3,142 ) and a two-phase , cross-sectional r and om sample of household residents ( N=10,108 ) were assessed with structured question naires and the semistructured Schedules for Clinical Assessment in Neuropsychiatry . RESULTS The weighted prevalence of probable functional psychosis in the past year was 4.5 per thous and ( 95 % CI=3.1 to 5.8 ) in the household survey . In the prison survey , the weighted prevalence was over 10 times greater : 52 per thous and ( 95 % CI=45 to 60 ) . One in four prisoners with a psychotic disorder had psychotic symptoms attributed to toxic or withdrawal effects of psychoactive substances . The proportion of subjects with specific types of hallucinations or delusions did not differ between prison and household psychosis cases . CONCLUSIONS This large study using st and ardized comparisons showed that the prevalence of psychosis in prisons is substantially higher than in the community and is deserving of greater attention to treatment and prevention . Apart from a minority of prisoners with symptoms attributable to psychoactive substances , the clinical symptom profile of psychosis is the same in both setting s. Longitudinal research is needed to better underst and these prevalence differences The Dissociative Experiences Scale was administered to a r and om sample of 1,055 adults in the city of Winnipeg . Results showed that scale scores did not differ between men and women and were not influenced by income , employment status , education , place of birth , religious affiliation , or number of persons in the respondent 's household . Dissociative experiences are common in the general population and decline with age . The findings suggest that dissociative disorders may also be common in the general population Prospect i ve longitudinal investigations are needed to identify causal processes leading to schizophrenia . However , there is presently no cost-effective way to identify children who are at risk of developing schizophrenia spectrum disorders : Although having a family history of schizophrenia is associated with elevated risk for developing spectrum disorders , the majority of individuals with schizophrenia do not have an afflicted relative . The present study aim ed to test the feasibility of screening a community sample of children , aged 9 to 12 years , to identify children who experienced a triad of putative antecedents of schizophrenia that had been identified from previous research , including : ( 1 ) speech and /or motor development lags or problems ; ( 2 ) social , emotional , or behavioural problems ; and ( 3 ) psychotic-like-experiences ( PLEs ) . 548 children and 264 caregivers completed question naires . 9.2 % of boys and 4.1 % of girls displayed the triad of antecedents . 58.9 % of the children reported \" certain experience \" of one or more PLEs . The results suggest that question naire screening of community sample s of children for the putative antecedents of schizophrenia spectrum disorders is feasible . Accuracy of identification will only be established by follow-up studies This article presents a prospect i ve analysis of an antecedent psychopathologic features and sociodemographic risk factors in schizophrenia with data from five community sites in the National Institute of Mental Health Epidemiologic Catchment Area Program . Three nonoverlapping psychotic cases were defined using DSM-III definitions as implemented by the Diagnostic Interview Schedule ( DIS ) : ( 1 ) DSM-III Schizophrenia Criterion A ; ( 2 ) Criterion A and Affective Episode ; and ( 3 ) full Schizophrenia . In a 1-year follow-up period , the cumulative incidence rate of Criterion A was 0.79 per 100 , for Criterion A with Affective Episode it was 0.17 per 100 , and for Schizophrenia the rate was 0.20 per 100 . In multivariable logistic regression modeling , the patterns of associations between sociodemographic factors and DIS/DSM-III Schizophrenia resembled patterns in clinical ly based registry data . Male subjects had an earlier peak onset than female subjects , and marital status and employment were strongly related to odds of developing DIS/DSM-III Schizophrenia . An interaction between gender and never marrying showed never-married men at 50 times higher odds of developing DIS/DSM-III Schizophrenia , never-married women at 14 times higher odds , and married women at 2.5 times higher odds , relative to married men . Adjusting for sociodemographic factors , DIS/DSM-III Obsessive Compulsive Disorder and Social Phobia were both associated with more than 3.5 times increased odds of developing DIS/DSM-III Schizophrenia . Several other psychopathology items , including panic attacks , were associated with increased odds of developing DIS/DSM-III Schizophrenia . There were both similarities and differences in risk factor structure between DIS/DSM-III Schizophrenia and the other two defined categories of case BACKGROUND Urban and rural population s have different rates of psychotic illness . If psychosis exists as a continuous phenotype in nature , urban-rural population differences in the rate of psychotic disorder should be accompanied by similar differences in the rate of abnormal mental states characterized by psychotic or psychosislike symptoms . METHODS A r and om sample of 7076 individuals aged 18 to 64 years were interviewed by trained lay interviewers with the Composite International Diagnostic Interview . Approximately half of those with evidence of psychosis according to the Composite International Diagnostic Interview were additionally interviewed by clinicians . We investigated associations between a 5-level urbanicity rating and ( 1 ) any DSM-III-R diagnosis of psychotic disorder ( sample prevalence , 1.5 % ) , ( 2 ) any rating of hallucinations and /or delusions ( sample prevalence , 4.2 % ) , and ( 3 ) any rating of psychotic or psychosislike symptoms ( sample prevalence , 17.5 % ) . RESULTS Level of urbanicity was associated not only with DSM-III-R psychotic disorder ( adjusted odds ratio [ OR ] over 5 levels , 1.47 ; 95 % confidence interval [ CI ] , 1.25 - 1.72 ) , but also , independently , with any rating of delusion and /or hallucination ( adjusted OR , 1.28 ; 95 % CI , 1.17 - 1.40 ; clinician-assessed psychotic symptoms only : OR , 1.30 ; 95 % CI , 1.03 - 1.64 ) and any rating of psychosislike symptom ( adjusted OR , 1.18 ; 95 % CI , 1.13 - 1.24 ) . Psychotic symptoms were strongly and independently associated with psychotic disorder , regardless of the level of urbanization . CONCLUSIONS Community level of psychotic and psychosislike symptoms may be inextricably linked to the prevalence of psychotic disorder . The prevalence of abnormal mental states that facilitate development to overt psychotic illness increases progressively with level of urbanization Abstract . Aims : The cross-sectional association between tobacco use and psychotic features has been well established . If psychotic features precede tobacco use , then tobacco may be used to self-medicate psychotic symptoms . The aim was to assess if psychotic features in adolescents constitute a risk factor for later tobacco use . Design : A r and om target sample of 2,600 children aged 4–16 years from the Dutch general population was followed up across a 14-year interval \n Output:\n " }, { "from": "agent", "value": "There is evidence , however , that transitory developmental expression of psychosis ( psychosis proneness ) may become abnormally persistent ( persistence ) and subsequently clinical ly relevant ( impairment ) , depending on the degree of environmental risk the person is additionally exposed to .\nThe psychosis proneness-persistence-impairment model considers genetic background factors impacting on a broadly distributed and transitory population expression of psychosis during development , poor prognosis of which , in terms of persistence and clinical need , is predicted by environmental exposure interacting with genetic risk" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: STUDY DESIGN Controlled cohort repeated- measures experimental design . OBJECTIVES To determine if a neuromuscular training program ( NMTP ) focused on core stability and lower extremity strength would affect performance on the star excursion balance test ( SEBT ) . We hypothesized that NMTP would improve SEBT performance in the experimental group and there would be no side-to-side differences in either group . BACKGROUND The SEBT is a functional screening tool that is used to assess dynamic stability , monitor rehabilitation progress , assess deficits following an injury , and identify athletes at high risk for lower extremity injury . The SEBT requires lower extremity coordination , balance , flexibility , and strength . METHODS Twenty uninjured female soccer players ( 13 experimental , 7 control ) participated . Players trained together as a team , so group allocation was not r and omized . The SEBT was administered prior to and following 8 weeks of NMTP in the experimental group and 8 weeks of no NMTP in the control group . A 3-way mixed-model ANOVA was used to determine the effect of group ( experimental versus control ) , training ( pretraining versus posttraining ) , and limb ( right versus left ) . RESULTS After participation in a NMTP , subjects demonstrated a significant improvement in the SEBT composite score ( mean ± SD ) on the right limb ( pretraining , 96.4 % ± 11.7 % ; posttraining , 104.6 % ± 6.1 % ; P = .03 ) and the left limb ( pretraining , 96.9 % ± 10.1 % ; posttraining , 103.4 % ± 8.0 % ; P = .04 ) . The control group had no change on the SEBT composite score for the right ( pretraining , 95.7 % ± 5.2 % ; posttraining , 94.4 % ± 5.2 % ; P = .15 ) or the left ( 97.4 % ± 7.2 % ; 93.6 % ± 5.0 % ; P = .09 ) limb . Further analysis identified significant improvement for the SEBT in the posterolateral direction on both the right ( P = .008 ) and left ( P = .040 ) limb and the posteromedial direction of the left limb ( P = .028 ) in the experimental group . CONCLUSION Female soccer players demonstrated an improved performance on the SEBT after NMTP that focused on core stability and lower extremity strength STUDY DESIGN Prospect i ve cohort . OBJECTIVE To determine if Star Excursion Balance Test ( SEBT ) reach distance was associated with risk of lower extremity injury among high school basketball players . BACKGROUND Although balance has been proposed as a risk factor for sports-related injury , few research ers have used a dynamic balance test to examine this relationship . METHODS AND MEASURES Prior to the 2004 basketball season , the anterior , posteromedial , and posterolateral SEBT reach distances and limb lengths of 235 high school basketball players were measured bilaterally . The Athletic Health Care System Daily Injury Report was used to document time loss injuries . After normalizing for lower limb length , each reach distance , right/left reach distance difference , and composite reach distance were examined using odds ratio and logistic regression analyses . RESULTS The reliability of the SEBT components ranged from 0.82 to 0.87 ( ICC3,1 ) and was 0.99 for the measurement of limb length . Logistic regression models indicated that players with an anterior right/left reach distance difference greater than 4 cm were 2.5 times more likely to sustain a lower extremity injury ( P<.05 ) . Girls with a composite reach distance less than 94.0 % of their limb length were 6.5 times more likely to have a lower extremity injury ( P<.05 ) . CONCLUSIONS We found components of the SEBT to be reliable and predictive measures of lower extremity injury in high school basketball players . Our results suggest that the SEBT can be incorporated into preparticipation physical examinations to identify basketball players who are at increased risk for injury Background : Youth baseball players are at high risk for elbow injuries , which can lead to future functional disability . Purpose : To evaluate the effectiveness of a prevention program to lower the risk of medial elbow injury in these athletes . Study Design : Cohort study ; Level of evidence , 2 . Methods : Youth baseball players , 8 to 11 years old , without a history of elbow and shoulder pain , were allocated to either the intervention ( n = 136 ) or control ( n = 169 ) group . The intervention consisted of 9 strengthening and 9 stretching exercises , performed during warm-up or at home , with high compliance defined as completion of the program 1 or more times per week . The following outcome variables were measured : clinical assessment of the elbow and shoulder joint , ultrasonography assessment of the elbow , and assessment of physical function ( passive range of motion of the elbow , shoulder , and hip ; strength of the shoulder and scapular muscles ; and measurement of the thoracic kyphosis angle ) . The clinical and ultrasonography assessment s were measured at baseline and at 3-month intervals over the 1-year follow-up . Physical function outcomes were measured at baseline and at the endpoint of the follow-up . The primary endpoint of effectiveness was the incidence of medial elbow injury . Secondary endpoints were absolute measures of physical function and change in these measures over the 1-year follow-up . Results : The incidence rate of medial elbow injury was significantly lower in the intervention group ( 0.8/1000 athlete-exposures ) than the control group ( 1.7/1000 athlete-exposures ) ( hazard ratio , 50.8 % ; 95 % CI , 0.292 - 0.882 ; P = .016 ) . The program improved total range of shoulder rotation ( dominant side ) , hip internal rotation ( nondominant side ) , shoulder internal rotation deficit ( bilaterally ) , lower trapezius muscle strength ( dominant side ) , and the thoracic kyphosis angle . Improvements in the following variables of physical function were predictive of a lower rate of medial elbow injury : increased total shoulder total rotation ( odds ratio [ OR ] , 0.973 ; 95 % CI , 0.950 - 0.997 ) , increased hip internal rotation of the nondominant side ( OR , 0.962 ; 95 % CI , 0.936 - 0.989 ) , and decreased thoracic kyphosis angle ( OR , 1.058 ; 95 % CI , 1.015 - 1.103 ) . Conclusion : A prevention program aim ing to improve physical function can prevent medial elbow injury in youth baseball players HYPOTHESIS AND BACKGROUND Though commonly suggested as an injury risk factor , scapular dysfunction has not been established as a prospect i ve cause of throwing-related upper extremity injury in baseball players . The purpose is to determine whether scapular dysfunction identified during preseason screening is predictive of increased risk of throwing-related shoulder and elbow injuries in high school baseball players . MATERIAL S AND METHODS The presence or absence of scapular dysfunction was obtained prospect ively during preseason screenings in 246 high school baseball players over the 2010 and 2011 seasons . Exposure and injury surveillance data were then obtained weekly over the course of each season to determine whether scapular dysfunction was predictive of subsequent throwing-related upper extremities sustained . RESULTS There were 12 throwing-related upper extremity injuries sustained in the 246 participants , yielding an injury rate of 1.0 per 1,000 athlete exposures . There were no significant differences in injury rates between the participants with normal scapular function versus subtle scapular dysfunction ( P = .62 ) , normal scapular function versus obvious scapular dysfunction ( P = .26 ) , or subtle versus obvious scapular dysfunction ( P = .45 ) . CONCLUSION This study showed that scapular dysfunction identified during preseason screenings is not associated with subsequent throwing-related upper extremity injury Background : Shoulder strength and motion deficits in high school baseball pitchers have been implicated in injury risk . Purpose /Hypothesis : To prospect ively determine if preseason strength and range of motion ( ROM ) are predictive of injury in high school baseball pitchers . It was hypothesized that ROM asymmetries and weakness would be predictive of injury . Study Design : Case-control study ; Level of evidence , 3 . Methods : Preseason strength and ROM measurements were made on 101 pitchers from 4 different high schools over 4 seasons ( total 166 pitcher-seasons : 25 freshman , 46 junior varsity , and 95 varsity player-seasons ) . Glenohumeral internal rotation ( IR ) , glenohumeral external rotation , and posterior shoulder ROM were measured bilaterally . Strength in IR , external rotation , supraspinatus ( empty-can test ) , and scapular retraction was measured bilaterally ( h and held dynamometer ) . Injury incidence ( injuries per 1000 pitches ) was computed for players categorized as above normal ( ≥1 SD above the mean ) , normal ( within 1 st and ard deviation of the mean ) , and below normal ( ≤1 SD below the mean ) for each potential risk factor . Injury was defined as a missed game or practice because of shoulder or elbow problem . Results : There were 28 upper extremity injuries ( 19 shoulder , 9 elbow ; incidence , 0.58 injuries/1000 pitches ) . There was a trend for supraspinatus weakness to be associated with increased injury risk ( relative risk [ RR ] , 3.60 ; 95 % CI , 0.75 - 17.32 ; P = .09 ) . When analyzing major injuries only ( > 3 missed games ) , preseason supraspinatus weakness was significantly associated with increased injury risk ( RR , 4.58 ; 95 % CI , 1.40 - 15.01 ; P = .02 ) . Paradoxically , pitchers with no IR loss were at increased risk compared with pitchers with ≥20 ° loss ( RR , 4.85 ; 95 % CI , 1.01 - 23.29 ; P = .04 ) . Other ROM and strength measures were unrelated to injury risk . Conclusion : Although excessive loss of IR ROM is thought to be a risk factor for injury , the opposite was the case in this study . The absence of IR ROM loss in high school pitchers may indicate inadequate prior exposure to pitching , result ing in increased injury risk . Preseason supraspinatus weakness was associated with increased risk for a major injury , and preventative supraspinatus strengthening may be beneficial Background : Throwing injuries of the shoulder and elbow are common among youth baseball players . Hypothesis : A prevention program will reduce the incidence of throwing injuries of the shoulder and elbow by 50 % among youth baseball players . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : The authors block r and omized 16 youth baseball teams consisting of 237 players aged 9 to 11 years into an intervention group ( 8 teams , 117 players ) and a control group ( 8 teams , 120 players ) . The intervention program consisted of 5 stretching , 2 dynamic mobility , and 2 balance training exercises performed during warm-up . Both groups were followed up for 12 months , during which the incidence of shoulder and elbow injuries was recorded . In addition , ball speed during pitching as a performance-related factor and variables of physical function ( passive range of motion of the elbow , shoulder and hip , dynamic balance , and thoracic kyphosis angle ) were assessed during the pre- and postintervention periods . Results : The incidence of shoulder and elbow injuries in the intervention group ( 1.7 per 1000 athlete-exposures ) was significantly lower than that in the control group ( 3.1 per 1000 athlete-exposures ) ( hazard ratio , 1.940 ; 95 % CI , 1.175 - 3.205 ; P = .010 ) . The factors related to pitching performance , as assessed by ball speed , tended to increase in the intervention group as compared with the control group ( P = .010 ) . The program also improved shoulder horizontal adduction deficits on the dominant side , hip internal rotation on the nondominant side , and the thoracic kyphosis angle . Conclusion : A prevention program decreases throwing injuries of the shoulder and elbow and enhances the parameter of pitching performance in youth baseball players \n Output:\n " }, { "from": "agent", "value": "Specific lower extremity deficits were found to be independent risk factors for elbow pain and injury in throwing athletes at certain levels of play .\nAdditionally , prevention programs design ed to correct deficits in identified risk factors were effective in reducing the incidence of elbow injury in youth athletes .\nThese results highlight the potential of screening and subsequent intervention to reduce the incidence of elbow injury in certain subsets of baseball players" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: INTRODUCTION Since 1994 we perform laparoscopic total extraperitoneal hernia repair ( TEP ) for primary and recurrent inguinal hernias at our institution . The aim of this study was to investigate and compare the results of TEP in primary inguinal hernias and recurrent inguinal hernias and to determine whether there are differences in patient data , complication rates and outcome between these two groups . METHODS In a prospect i ve trial 338 patients were analyzed who underwent 500 laparoscopic TEP repairs . In all , 431 TEP repairs were performed for primary inguinal hernias , and 69 for recurrent inguinal hernias . For data acquisition the SALTC study protocol was used . All patients were clinical ly examined 3 and 12 months after the operation . RESULTS The mean operation time was 67.3 min for TEP repair of primary hernias and 68.1 min for TEP repair of recurrent hernias , respectively . The conversion rate to an open procedure was 0 % . Conversion from TEP into TAPP was required in 0.5 % of patients with primary inguinal hernias and 1.4 % of patients with recurrent inguinal hernias . As the sole difference between the two groups the intraoperative complication rate could be identified . In the TEP repair group of recurrent inguinal hernias a higher incidence of injury to the peritoneum and a higher occurrence of bleeding from the epigastric vessels was found ( P = 0.03 ) . The postoperative complication rate was identical in the two groups , amounting to 5.1 % and 5.7 % , respectively . No differences were found in the 1 year follow-up between the two groups . The 1-year recurrence rate was 0.5 % for primary hernias . However , in the group of recurrent hernias there have been no recurrences to date . CONCLUSIONS The use of laparoscopic TEP repair has proven to be a safe and effective treatment in patients with primary and recurrent inguinal hernias . Because of scar tissue with possible adhesions a higher intraoperative complication rate was observed in the TEP repair of recurrent hernias than in TEP repair of primary inguinal hernias . However , no single recurrence was observed in the TEP repair group of recurrent hernias . In our opinion TEP is the optimal hernia repair for recurrent and bilateral inguinal hernias BACKGROUND For many years it has been cl aim ed that observational studies find stronger treatment effects than r and omized , controlled trials . We compared the results of observational studies with those of r and omized , controlled trials . METHODS We search ed the Abridged Index Medicus and Cochrane data bases to identify observational studies reported between 1985 and 1998 that compared two or more treatments or interventions for the same condition . We then search ed the Medline and Cochrane data bases to identify all the r and omized , controlled trials and observational studies comparing the same treatments for these conditions . For each treatment , the magnitudes of the effects in the various observational studies were combined by the Mantel-Haenszel or weighted analysis -of-variance procedure and then compared with the combined magnitude of the effects in the r and omized , controlled trials that evaluated the same treatment . RESULTS There were 136 reports about 19 diverse treatments , such as calcium-channel-blocker therapy for coronary artery disease , appendectomy , and interventions for subfertility . In most cases , the estimates of the treatment effects from observational studies and r and omized , controlled trials were similar . In only 2 of the 19 analyses of treatment effects did the combined magnitude of the effect in observational studies lie outside the 95 percent confidence interval for the combined magnitude in the r and omized , controlled trials . CONCLUSIONS We found little evidence that estimates of treatment effects in observational studies reported after 1984 are either consistently larger than or qualitatively different from those obtained in r and omized , controlled trials Background : A variety of procedures with substantial differences in results are employed to treat recurrent inguinal hernia . The advantages of totally extraperitoneal patch repair ( TEP ) are even more evident when it is applied to recurrent compared to primary hernias . To investigate the superiority of this method more closely , we review ed our results obtained for recurrent inguinal hernias over a period of 2 years . Methods : We performed a prospect i ve single-center study using data obtained in consecutive patients with recurrent inguinal hernia who were operated on in 1997 and 1998 . Results : A total of 179 patients with recurrent inguinal hernia were recruited . Overall , 1329 patients with inguinal hernia were treated in the 2-year period , of whom 1270 underwent TEP . The percentage of recurrent hernias was 14 % . The average age of the patients was 56 years . The follow-up rate was 87.5 % , and the mean follow-up period was 2.3 years . The 154 patients who were followed up underwent a total of 225 hernia repairs , of which 181 were for recurrent hernias . The average operating time was 57 min . In 68 % ( 104/154 ) of the patients , adhesions , adherent epigastric vessels , or cicatricial changes were found , which result ed in the inadvertant opening of the peritoneum in 26.3 % of the patients . All the openings in the peritoneum were closed by endoscopic suturing . Intraoperative complications developed in 4 patients ( 2.3 % ) , including one injury to the bladder and three cases of bleeding from side branches of the epigastric vessels . The conversion rate was 0 % . The sole postoperative complication was treatment requiring hematomas in 7 patients , in 2 of whom reoperation became necessary . In both cases , a diffuse hemorrhage due to a preoperatively undiagnosed coagulation disorder was found . No cases of wound or patch infection were observed . In a patient undergoing both primary and recurrent hernia repair , displacement of a mesh led to a recurrence on the primary hernia side ( recurrence rate , 0.4 % ; re-recurrence rate , 0 % ) . Conclusions : Although for its definitive management , recurrent hernia requires a reliable operative technique , current data do not support the recommendation of any of the currently available procedures as the gold st and ard . In a representative patient population with recurrent hernia , we were able to demonstrate that TEP achieves very good results in terms of re-recurrence rate , intraoperative and postoperative complications , and rehabilitation . Prerequisites for the reliable and low-complication application of the method are a high level of st and ardization of the procedure and an advanced learning curve Evidence -based medicine ( EBM ) ranks different medical research methods on a hierarchy , at the top of which are r and omized controlled trials ( RCTs ) and systematic review s or meta-analyses of RCTs . Any study that does not r and omly assign patients to a treatment or a control group is automatically placed at a lower level on the hierarchy . This article argues that what matters is whether the treatment and control groups are similar with respect to potential confounding factors , not whether they got that way through r and omization . Moreover , nonr and omized studies tend to have other characteristics that make them useful sources of evidence , in that they tend to last longer and to enroll more patients than do r and omized trials . Replacing the sharp dichotomy between r and omized and nonr and omized studies with a continuum from “ clean ” studies ( which have high internal validity but whose results do not readily generalize to clinical practice ) to pragmatic studies ( which are design ed to more closely reflect clinical practice ) would also make a place for outcomes research and research using clinical data bases , which are not included in the current hierarchy of evidence but which can provide important information about the safety and efficacy of treatments Background : The aim of this study was to investigate the outcome of preperitoneal repair using laparoscopic ( TEP ) and open ( OPM ) approach in recurrent inguinal hernia . Methods : We performed a prospect i ve controlled nonr and omized clinical study in 188 patients with 207 recurrent inguinal hernias over a period of 5 years . TEP repair was employed for 86 repairs , and OPM was used in 121 procedures . The main outcome measurements were : recurrence rate , operating time , hospital stay , and postoperative complications . Results : There were three recurrences ( 1.7 % ) . Two in the OPM group ( 1.8 % ) and one ( 1.3 % ) in the TEP group [ P = NS ( not significant ) ] . The TEP procedure was faster than OPM for unilateral repair ( 40.8 vs 46.3 min ) ( P<0.001 ) . Postoperative complications were more frequent in the OPM group ( 23.9 % ) than the TEP group ( 13.9 % ) ( P = NS ) . Hospital stay was significantly shorter in the TEP group ( 1.2 vs 3.9 days ) ( P<0.001 ) . Conclusions : Preperitoneal approach ( open or laparoscopic ) seems to be a good option in recurrent inguinal hernia when these procedures are done by experienced surgeons Introduction The Lichtenstein hernioplasty for the repair of primary inguinal hernia in male patients is well established and constitutes the current gold st and ard . However a gold st and ard technique for the repair of recurrent inguinal hernia has not been established . The aim of this study was to analyze the outcomes of Lichtenstein hernioplasty for the repair of primary inguinal hernia and recurrent inguinal hernia , applying for that purpose the Qualitative and Quantitative Measurement Instrument ( QQMI ) . Methods We studied 75 recurrent inguinal hernia patients and 287 primary inguinal hernia patients with a follow-up period ranging from 60 to 107 months . Results The final QQMI score demonstrated that most patients in both groups reached scores between 8 and 11 points , with a significant difference in the maximum score ( 11 points ) favoring primary hernia patients . Conclusions All evaluated parameters showed better outcomes in primary hernia patients . Applying the QQMI , we have demonstrated that the outcomes of Lichtenstein hernioplasty are not similar between primary and recurrent inguinal hernia ; there is a tendency toward better outcomes for primary inguinal hernia patients , although the Lichtenstein hernioplasty st and s as a safe option for repair of recurrent inguinal hernias Objective : To compare the Lichtenstein hernioplasty with a totally extraperitoneal preperitoneal laparoscopic technique ( TEP ) in treatment of recurrent inguinal hernias . Summary Background Data : Only a few studies thus far have compared an open and laparoscopic approach with the treatment of recurrent inguinal hernia in a prospect i ve r and omized study setting . Methods : Ninety-nine patients undergoing surgery for recurrent inguinal hernia were prospect ively r and omized into having either open or laparoscopic mesh repair . Pre , peri- and postoperative factors were recorded in addition to 3-year follow-up data at the outpatient clinic . At 5–10 years , the patients were interviewed via telephone for recurrent symptoms . The primary end-points chosen were hernia recurrence and chronic pain . Results : Preoperative factors did not differ between the 2 groups . Rerecurrence rates were 3 in the Lichtenstein group and none in the TEP group ( 6.4 % versus 0.0 % , respectively ) , but this difference was statistically not significant . Chronic pain was more prevalent in the Lichtenstein group compared with the TEP group ( 13 [ 27.7 % ] versus 4 [ 8.2 % ] patients , respectively , P = 0.02 ) . Postoperatively , the Lichtenstein group needed more pain medication than the TEP group ( 4.4 versus 3.0 doses , respectively , P = 0.02 ) and returned to work later ( 17.9 versus 14.8 days , respectively , P = 0.05 ) . Conclusions : The laparoscopic technique with mesh in the treatment of recurrent inguinal hernia was proven superior to the open mesh repair in several important clinical aspects , with concomitant improvement in patient satisfaction Background Recurrences continue to be seen after repair of inguinal hernias . The repair of these recurrent hernias is a more complex and dem and ing procedure , with a high re-recurrence rate . Definite advantage has been demonstrated with endoscopic repair of these hernias . Methods The results for this prospect i ve study from January 2003 to December 2006 were evaluated after laparoscopic repair of 65 recurrent hernias in 61 patients . The patients were followed up for 1 year . Longer follow-up evaluation was performed for the patients who underwent surgery in the initial 3 years . Results In this study , 37 recurrent hernias were managed using the transabdominal preperitoneal technique ( TAPP ) technique and 28 using the totally extraperitoneal ( TEP ) technique . There was no conversion and no cases of postoperative wound infection . Of the 12 metachronous hernias repaired simultaneously , 3 were occult . Seroma developed in five patients . At a follow-up assessment after 1 year , one patient had groin pain , and there was one re-recurrence . A longer follow-up period with a mean of 35.11 months failed to show any new re-recurrence . Conclusions Laparoscopic repair of recurrent inguinal hernia is safe and effective . The morbidity and recurrence rates for the procedure are as low as for laparoscopic repair of primary hernias . Laparoscopic repair should be the gold st and ard for these hernias Background The optimal treatment for recurrent inguinal hernia is of concern due to the high frequency of recurrence . Methods This r and omized multicenter study compared the short- and long-term results for recurrent inguinal hernia repair by either the laparoscopic transabdominal \n Output:\n " }, { "from": "agent", "value": "Comparisons of all outcomes in N RCTs and RCTs failed to show statistical significance .\nProspect ive/retrospective cohort studies , case series , and RCTs did not differ significantly in their estimates .\nAdjusted testing for metaregression disclosed that rerecurrence among N RCTs was independent of the study design .\nThe number of included patients and study setting were independent predictors of outcome ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Abstract Objective : To examine the use of evidence based leaflets on informed choice in maternity services . Design : Non-participant observation of 886 antenatal consultations . 383 in depth interviews with women using maternity services and health professionals providing antenatal care . Setting : Women 's homes ; antenatal and ultrasound clinics in 13 maternity units in Wales . Participants : Childbearing women and health professionals who provide antenatal care . Intervention : Provision of 10 pairs of Informed Choice leaflets for service users and staff and a training session in their use . Main outcome measures : Participants ' views and commonly observed responses during consultations and interviews . Results : Health professionals were positive about the leaflets and their potential to assist women in making informed choices , but competing dem and s within the clinical environment undermined their effective use . Time pressures limited discussion , and choice was often not available in practice . A widespread belief that technological intervention would be viewed positively in the event of litigation reinforced notions of “ right ” and “ wrong ” choices rather than “ informed ” choices . Hierarchical power structures result ed in obstetricians defining the norms of clinical practice and hence which choices were possible . Women 's trust in health professionals ensured their compliance with professionally defined choices , and only rarely were they observed asking questions or making alternative requests . Midwives rarely discussed the contents of the leaflets or distinguished them from other literature related to pregnancy . The visibility and potential of the leaflets as evidence based decision aids was thus greatly reduced . Conclusions : The way in which the leaflets were disseminated affected promotion of informed choice in maternity care . The culture into which the leaflets were introduced supported existing normative patterns of care and this ensured informed compliance rather than informed choice . What is already known on this topic Informed Choice leaflets are widely used in maternity care but little is known about their ability to influence informed choice and decision making High quality information is essential for promoting informed choice but is insufficient by itself What this study adds Time constraints and other pressures on health professionals result ed in a lack of discussion of the content of the leaflets Fear of litigation , power hierarchies , and the technological imperative in maternity care limited the choices available Health professionals promoted normative practice s rather than choice , and as women valued their opinions this led to the promotion of informed compliance rather than informed OBJECTIVE To examine the causal effects of doctor-patient relations and the severity of a medical outcome on medical patient perceptions and mal practice intentions in the event of an adverse medical outcome . DESIGN R and omized between-subjects experimental design . Patients were given scenarios depicting interactions between an obstetric patient and her physician throughout the patient 's pregnancy , labor , and delivery . PARTICIPANTS One hundred twenty-eight postpartum obstetric patients were approached for participation , of whom 104 completed the study . Main outcome measures Patients ' perceptions of physician competence and intentions to file a mal practice cl aim . RESULTS Positive physician communication behaviors increased patients ' perceptions of physician competence and decreased mal practice cl aim intentions toward both the physician and the hospital . A more severe outcome increased only patients ' intentions to sue the hospital . CONCLUSION These results provide empiric evidence for a direct , causal effect of the doctor-patient relationship on medical patients ' treatment perceptions and mal practice cl aim intentions in the event of an adverse medical outcome BACKGROUND Informed consent forms should document and reflect the goals of informed consent and shared decision making . We conducted this study to examine the extent to which informed consent for procedure forms meet accepted informed consent st and ards , how well state informed consent statutes correlate with these st and ards , and whether existing forms can enhance the interactions between patients and physicians or other health care providers . HYPOTHESIS Informed consent forms do not meet accepted st and ards . A different format may be more useful for patient-physician interactions . DESIGN A content analysis was conducted of hospital informed consent for procedure forms from a r and om selection of hospitals in the 1994 American Hospital Association membership directory . Forms were examined for evidence of the basic elements of informed consent ( nature of the procedure , risks , benefits , and alternatives ) and items that might enhance patient-physician interactions and encourage shared decision making . UNIT OF ANALYSIS : From 157 hospitals nationwide , 540 hospital informed consent for procedure forms were examined . MEASUREMENTS AND MAIN RESULTS Ninety-six percent of forms indicated the nature of the procedure , but risks , benefits , and alternatives were found less often . Only 26 % of forms included all 4 basic elements , 35 % included 3 of 4 elements , 23 % had 2 of 4 elements , 14 % had only 1 element , and 2 % had none of the elements . Forms appear to authorize treatment ( 75 % ) or protect hospitals and caregivers from liability ( 59 % ) rather than clarify information about procedures ( 40 % ) or aid patients in decision making ( 14 % ) . Forms from states with statutes that require that all 4 elements be provided were no more likely than other states to include them ( Fisher exact test = 1.000 ) . Fewer than 40 % of forms supported models of shared decision making . CONCLUSIONS The content of most forms did not meet accepted st and ards of informed consent or patient-physician interactions . We propose a form that more fully supports the models of ideal informed consent and shared decision making to enhance the applicability of informed consent in the clinical setting OBJECTIVE To ascertain general practitioners ' perceptions of medicolegal risk when screening for prostate cancer , and explore the potential impact of three national guidelines on perceptions and clinical practice . DESIGN Postal survey in August 1997 . PARTICIPANTS 219 r and omly selected GPs in New South Wales ( 65 % response rate ) . MAIN OUTCOME MEASURES Response to case scenarios ; perceptions of medicolegal risk and protection afforded by national guidelines before and after reading extracts of three national guidelines ; ratings of current and potential strategies to increase GPs ' sense of medicolegal protection . RESULTS 90 % ( 95 % CI , 86.5%-94.3 % ) would screen an asymptomatic male patient and 61 % ( 95 % CI , 54.2%-67.2 % ) indicated GPs would be at risk if they did not screen . Although significant changes in responses were found after respondents had read guideline extracts , 46 % ( 95 % CI , 39.5%-52.7 % ) continued to perceive medicolegal risk if screening was not performed . About two-thirds ( 65 % ; 95 % CI , 59.9%-72.5 % ) supported a clear statement about the legal status of guidelines in a court of law to increase their sense of medicolegal protection . CONCLUSIONS Even when made aware of national evidence -based guidelines against prostate cancer screening , GPs in our survey perceived limited hypothetical medicolegal protection Decision aids are evidence -based sources of health information that can help patients make informed treatment decisions . However , little is known about how decision aids affect health care use when they are implemented outside of r and omized controlled clinical trials . We conducted an observational study to examine the associations between introducing decision aids for hip and knee osteoarthritis and rates of joint replacement surgery and costs in a large health system in Washington State . Consistent with prior r and omized trials , our introduction of decision aids was associated with 26 percent fewer hip replacement surgeries , 38 percent fewer knee replacements , and 12 - 21 percent lower costs over six months . These findings support the concept that patient decision aids for some health conditions , for which treatment decisions are highly sensitive to both patients ' and physicians ' preferences , may reduce rates of elective surgery and lower costs OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity BACKGROUND The current literature does not provide an answer to the question , \" What prompts patients to sue doctors or hospitals ? \" Not all adverse outcomes result in suits , and threatened suits do not always involve adverse outcomes . The exploration of other factors has been hampered by the lack of a methodology to contact plaintiffs and elicit their views about their experience in delivered health care . This study employed the transcripts of discovery depositions of plaintiffs as a source of insight into the issues that prompted individuals to file a mal practice cl aim . METHODS This study is a descriptive series review of a convenience sample of 45 plaintiffs ' depositions selected r and omly from 67 depositions made available from settled mal practice suits filed between 1985 and 1987 against a large metropolitan medical center . Information extracted from each deposition included the alleged injury ; the presence of the question , \" Why are you suing ? \" and , if present , the answer ; the presence of problematic relationship issues between providers and patients and /or families and , if present , the discourse supporting it ; the presence of the question , \" Did a health professional suggest maloccurrence ? \" and , if yes , who . Using a process of consensual validation , relationship issues were organized into groups of more generalized categories suggested by the data . Answers to the questions , \" Why are you suing ? \" and \" Who suggested maloccurrence ? \" are described . RESULTS Problematic relationship issues were identified in 71 % of the depositions with an interrater reliability of 93.3 % . Four themes emerged from the descriptive review of the 3787 pages of transcript : deserting the patient ( 32 % ) , devaluing patient and /or family views ( 29 % ) , delivering information poorly ( 26 % ) , and failing to underst and the patient and /or family perspective ( 13 % ) . Thirty-one plaintiffs were asked if health professionals suggested maloccurrence . Fifty-four percent ( n = 17 ) responded affirmatively . The post outcome -consulting specialist was named in 71 % ( n = 12 ) of the depositions in which maloccurrence was allegedly suggested . CONCLUSIONS In our sample , the decision to litigate was often associated with a perceived lack of caring and /or collaboration in the delivery of health care . The issues identified included perceived unavailability , discounting patient and /or family concerns , poor delivery of information , and lack of underst and ing the patient and /or family perspective . Particular attention should be paid to the postadverse-event consultant-patient interaction OBJECTIVE To examine the relationship between prior physician mal practice experience and patients ' satisfaction with care . DESIGN Women were interviewed using a question naire that contained structured and open-ended questions . PARTICIPANTS Mothers of all stillborn infants , infant deaths , and a r and om sampling of viable infants drawn from 1987 Florida Vital Statistics were sorted into four groups based on the mal practice cl aims experience of their obstetricians between 1983 and 1986 . Interviews were completed with 963 of 1536 women , most by telephone , 53 by in-person interview . MAIN OUTCOME MEASURES Mothers ' responses to closed-ended and open-ended questions about their perceptions of the care they received during their pregnancy , labor , and delivery . RESULTS Even though none of the women actually filed a cl aim , a consistent pattern of differences emerged when comparing women 's perceptions of care received . Patients seeing physicians with the most frequent numbers of cl aims but without high payments were significantly more likely to complain that they felt rushed , never received explanations for tests , and were ignored . In response to the open-ended question , \" What part of your care were you least satisfied with ? \" women seeing physicians in the High Frequency mal practice risk group offered twice as many complaints as those seeing physicians who had never been sued . Problems with physician-patient communication were the most commonly offered complaints . CONCLUSION Physicians who have been sued frequently are more often the objects of complaints about the interpersonal care they provide even by their patients who do not sue \n Output:\n " }, { "from": "agent", "value": "The analysis confirms the absence of empirical data necessary to determine whether or not shared decision-making promoted in the clinical encounter can reduce litigation .\nThree out of five included studies provide retrospective and simulated data suggesting that ignoring or failing to diagnose patient preferences , particularly when no effort has been made to inform and support underst and ing of possible harms and benefits , puts clinicians at a higher risk of litigation .\nSimulated scenarios suggest that documenting the use of decision support interventions in patients ’ notes could offer some level of medico-legal protection .\nOur analysis also indicated that a sizeable proportion of clinicians prefer ordering more tests and procedures , irrespective of patient informed preferences , as protection against litigation .\nConclusions Given the lack of empirical data , there is insufficient evidence to determine whether or not shared decision-making and the use of decision support interventions can reduce medical mal practice litigation ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: PURPOSE To define outcome data and prognostic criteria for patients with metastatic renal cell carcinoma ( RCC ) treated with interferon-alfa as initial systemic therapy . The data can be applied to design and interpretation of clinical trials of new agents and treatment programs against this refractory malignancy . PATIENTS AND METHODS Four hundred sixty-three patients with advanced RCC administered interferon-alpha as first-line systemic therapy on six prospect i ve clinical trials were the subjects of this retrospective analysis . Three risk categories for predicting survival were identified on the basis of five pretreatment clinical features by a stratified Cox proportional hazards model . RESULTS The median overall survival time was 13 months . The median time to progression was 4.7 months . Five variables were used as risk factors for short survival : low Karnofsky performance status , high lactate dehydrogenase , low serum hemoglobin , high corrected serum calcium , and time from initial RCC diagnosis to start of interferon-alpha therapy of less than one year . Each patient was assigned to one of three risk groups : those with zero risk factors ( favorable risk ) , those with one or two ( intermediate risk ) , and those with three or more ( poor risk ) . The median time to death of patients deemed favorable risk was 30 months . Median survival time in the intermediate-risk group was 14 months . In contrast , the poor-risk group had a median survival time of 5 months . CONCLUSION Progression-free and overall survival with interferon-alpha treatment can be compared with new therapies in phase II and III clinical investigations . The prognostic model is suitable for risk stratification of phase III trials using interferon-alpha as the comparative treatment arm BACKGROUND The treatment of advanced renal cell carcinoma has been revolutionised by targeted therapy with drugs that block angiogenesis . So far , no phase 3 r and omised trials comparing the effectiveness of one targeted agent against another have been reported . We did a r and omised phase 3 study comparing axitinib , a potent and selective second-generation inhibitor of vascular endothelial growth factor ( VEGF ) receptors , with sorafenib , an approved VEGF receptor inhibitor , as second-line therapy in patients with metastatic renal cell cancer . METHODS We included patients coming from 175 sites ( hospitals and outpatient clinics ) in 22 countries aged 18 years or older with confirmed renal clear-cell carcinoma who progressed despite first-line therapy containing sunitinib , bevacizumab plus interferon-alfa , temsirolimus , or cytokines . Patients were stratified according to Eastern Cooperative Oncology Group performance status and type of previous treatment and then r and omly assigned ( 1:1 ) to either axitinib ( 5 mg twice daily ) or sorafenib ( 400 mg twice daily ) . Axitinib dose increases to 7 mg and then to 10 mg , twice daily , were allowed for those patients without hypertension or adverse reactions above grade 2 . Participants were not masked to study treatment . The primary endpoint was progression-free survival ( PFS ) and was assessed by a masked , independent radiology review and analysed by intention to treat . This trial was registered on Clinical Trials.gov , number NCT00678392 . FINDINGS A total of 723 patients were enrolled and r and omly assigned to receive axitinib ( n=361 ) or sorafenib ( n=362 ) . The median PFS was 6·7 months with axitinib compared to 4·7 months with sorafenib ( hazard ratio 0·665 ; 95 % CI 0·544 - 0·812 ; one-sided p<0·0001 ) . Treatment was discontinued because of toxic effects in 14 ( 4 % ) of 359 patients treated with axitinib and 29 ( 8 % ) of 355 patients treated with sorafenib . The most common adverse events were diarrhoea , hypertension , and fatigue in the axitinib arm , and diarrhoea , palmar-plantar erythrodysaesthesia , and alopecia in the sorafenib arm . INTERPRETATION Axitinib result ed in significantly longer PFS compared with sorafenib . Axitinib is a treatment option for second-line therapy of advanced renal cell carcinoma . FUNDING Pfizer Background Kidney and renal pelvis cancers account for 4 % of all new cancer cases in the United States , among which 85 % are renal cell carcinomas ( RCC ) . While cigarette smoking is an established risk factor for RCC , little is known about the contribution of environmental tobacco smoke ( ETS ) to RCC incidence . This study assesses the role of smoking and ETS on RCC incidence using a population -based case-control design in Florida and Georgia . Methods Incident cases ( n = 335 ) were identified from hospital records and the Florida cancer registry , and population controls ( n = 337 ) frequency-matched by age ( + /- 5 years ) , gender , and race were identified through r and om-digit dialing . In-person interviews assessed smoking history and lifetime exposure to ETS at home , work , and public spaces . Home ETS was measured in both years and hours of exposure . Odds ratios and 95 % confidence intervals were calculated using logistic regression , controlled for age , gender , race , and BMI . Results Cases were more likely to have smoked 20 or more pack-years , compared with never-smokers ( OR : 1.35 , 95 % CI : 0.93 – 1.95 ) . A protective effect was found for smoking cessation , beginning with 11–20 years of cessation ( OR : 0.39 , 95 % CI : 0.18–0.85 ) and ending with 51 or more years of cessation ( OR : 0.11 , 95 % CI : 0.03–0.39 ) in comparison with those having quit for 1–10 years . Among never-smokers , cases were more likely to report home ETS exposure of greater than 20 years , compared with those never exposed to home ETS ( OR : 2.18 ; 95 % CI : 1.14–4.18 ) . Home ETS associations were comparable when measured in lifetime hours of exposure , with cases more likely to report 30,000 or more hours of home ETS exposure ( OR : 2.37 ; 95 % CI : 1.20–4.69 ) . Highest quartiles of combined home/work ETS exposure among never-smokers , especially with public ETS exposure , increased RCC risk by 2 to 4 times . Conclusion These findings confirm known associations between smoking and RCC and establish a potential etiologic role for ETS , particularly in the home . Differences in methods of retrospective measurement of lifetime smoking and ETS exposure may contribute to discrepancies in measures of associations across studies , and should be addressed in future research Introduction : The Eastern Cooperative Oncology Group ( ECOG ) score is a well known prognostic factor and almost always used to determine eligibility for clinical trials . The patient-rated performance status score ( Pt-PS ) , section of the patient generated subjective global assessment scale , has identical criteria to the physician-rated ECOG scale ( MD-PS ) . We compared the Pt-PS with MD-PS in patients with advanced non-small cell lung cancer and compared the effect of each rating on eligibility for a hypothetical clinical trial . Methods : Consecutive patients with newly diagnosed advanced non-small cell lung cancer completed a patient generated subjective global assessment self-rated question naire , which was then correlated ( kappa statistic ) with the ECOG PS recorded at the same time . Patients were treated with st and ard chemotherapy . Survival was determined using Kaplan-Meier statistics . Results : One hundred nine patients ( M : F-54:55 ) were recruited . Pt-PS differed from MD-PS in 59 ( 54 % ) instances ( p = 0.0001 ) . When scores were not congruent , 41/59 ( 69 % ) patients evaluated themselves as having a worse PS than the physician ’s rating . Pt-PS was 0 to 1 in 60 ( 55 % ) patients whereas MD-PS was 0 to 1 in 78 ( 72 % ) patients . The functional status irrespective of evaluator was predictive of survival ( p = 0.001 for MD-PS and p = 0.001 for Pt-PS ) . However , the median survival in those with MD-PS ≥2 was 3.3 ( CI ; 1.7 - 4.9 ) months whereas individuals with Pt-PS ≥2 had a median survival of 6.2 ( CI ; 5.4 - 6.9 ) months . Conclusions : Pt-PS and MD-PS were not congruent in over half of the cases , with Pt-PS scores usually poorer . Almost half the patients would have excluded themselves from a hypothetical clinical trial ( Pt-PS ≥2 ) . This requires prospect i ve evaluation BACKGROUND Response patterns to nivolumab differ from those seen with other approved targeted therapies . OBJECTIVE To investigate the efficacy of nivolumab in previously treated patients with advanced renal cell carcinoma who were treated beyond ( Response Evaluation Criteria In Solid Tumors ) RECIST progression . DESIGN , SETTING , AND PARTICIPANTS This was a subgroup analysis of patients treated with nivolumab in the phase 3 CheckMate 025 study . Patients continuing to tolerate therapy and exhibiting investigator-assessed clinical benefit were eligible to be treated beyond RECIST progression ( TBP ) and received therapy for ≥4 wk after first progression ; patients not treated beyond RECIST progression ( NTBP ) received 0 wk to < 4 wk of therapy after progression . INTERVENTIONS Nivolumab 3mg/kg intravenously every 2 wk . RESULTS AND LIMITATIONS Of 406 nivolumab-treated patients , 316 ( 78 % ) progressed by RECIST criteria . Of those who progressed , 48 % were TBP , 52 % were NTBP . Before being TBP , objective response rate ( 95 % confidence interval ) was 20 % ( 14 - 28 ) and 14 % ( 9 - 21 ) in patients TBP and NTBP , respectively . Differences in clinical characteristics assessed at first progression between patients TBP versus NTBP included better Karnofsky performance status , less deterioration in Karnofsky performance status , shorter time to response , lower incidence of new bone lesions , and improved quality of life . Postprogression , 13 % of all patients TBP ( 20/153 ) had ≥30 % tumor burden reduction including patients with preprogression and postprogression tumor measurements ( n=142 ) and complete/partial response ( 28 % , 8/29 ) , stable disease ( 6 % , 3/47 ) , and progressive disease ( 14 % , 9/66 ) as their best response before being TBP . Incidence of treatment-related adverse events in patients TBP was lower after ( 59 % ) versus before ( 71 % ) progression . Limitations included potential bias from the nonr and omized nature of the analysis . CONCLUSIONS A subset of patients with advanced renal cell carcinoma and RECIST progression experienced tumor reduction postprogression with nivolumab , and had an acceptable safety profile . Clinical judgment remains essential when switching therapy . Clinical Trials.gov Identifier : NCT01668784 . PATIENT SUMMARY A subset of patients with advanced renal cell carcinoma and disease progression may continue to benefit from nivolumab treatment beyond progression as evidence d by tumor reduction postprogression and an acceptable safety profile \n Output:\n " }, { "from": "agent", "value": "Conclusions This study suggests that a poor PS is significantly associated with poor prognosis in mRCC patients receiving TKIs" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: We present a double-blind trial in which a pulsed infrared beam was compared with a placebo in the treatment of myofascial pain in the cervical region . The patients were su bmi tted to 12 sessions on alternate days to a total energy dose of 5 J each . At each session , the four most painful muscular trigger points and five bilateral homometameric acupuncture points were irradiated . Those in the placebo group su bmi tted to the same number of sessions following an identical procedure , the only difference being that the laser apparatus was nonoperational . Pain was monitored using the Italian version of the McGill pain question naire and the Scott-Huskisson visual analogue scale . The results show a pain attenuation in the treated group and a statistically significant difference between the two groups of patients , both at the end of therapy and at the 3-month follow-up examination OBJECTIVE The objective of the study was to investigate clinical effects of low-level laser therapy ( LLLT ) in patients with acute neck pain with radiculopathy . DESIGN Double-blind , r and omized , placebo-controlled study . SETTING The study was carried out between January 2005 and September 2007 at the Clinic for Rehabilitation at the Medical School , University of Bel grade , Serbia . PATIENTS AND INTERVENTION Sixty subjects received a course of 15 treatments over 3 weeks with active or an inactivated laser as a placebo procedure . LLLT was applied to the skin projection at the anatomical site of the spinal segment involved with the following parameters : wavelength 905 nm , frequency 5,000 Hz , power density of 12 mW/cm(2 ) , and dose of 2 J/cm(2 ) , treatment time 120 seconds , at whole doses 12 J/cm(2 ) . OUTCOME MEASURES The primary outcome measure was pain intensity as measured by a visual analog scale . Secondary outcome measures were neck movement , neck disability index , and quality of life . Measurements were taken before treatment and at the end of the 3-week treatment period . RESULTS Statistically significant differences between groups were found for intensity of arm pain ( P = 0.003 , with high effect size d = 0.92 ) and for neck extension ( P = 0.003 with high effect size d = 0.94 ) . CONCLUSION LLLT gave more effective short-term relief of arm pain and increased range of neck extension in patients with acute neck pain with radiculopathy in comparison to the placebo procedure OBJECTIVE We aim ed to evaluate the effectiveness of laser therapy in myofascial pain syndrome treatment . BACKGROUND DATA Myofascial pain syndrome is a disease that is characterized by hypersensitive points called trigger points found in one or more muscles and /or connective tissues . It can cause pain , muscle spasm , sensitivity , stiffness , weakness , limitation of range of motion and rarely autonomic dysfunction . Physical therapy modalities and exercise are used in the treatment of this frequently encountered disease . METHODS The placebo controlled , prospect i ve , long-term follow up study was planned with 60 patients who had trigger points in their upper trapezius muscles . The patients were divided into three groups r and omly . Stretching exercises were taught to each group and they were asked to exercise at home . Treatment duration was 4 weeks . Placebo laser was applied to group 1 , dry needling to group 2 and laser to group 3 . He-Ne laser was applied to three trigger points in the upper trapezius muscles on both sides with 632.8 nm . The patients were assessed at before , post-treatment , and 6 months after-treatment for pain , cervical range of motion and functional status . RESULTS We observed a significant decrease in pain at rest , at activity , and increase in pain threshold in the laser group compared to other groups . Improvement according to Nottingham Health Profile gave the superiority of the laser treatment . However , those differences among the groups were not observed at 6-month follow up . CONCLUSIONS Laser therapy could be useful as a treatment modality in myofascial pain syndrome because of its noninvasiveness , ease , and short-term application Abstract A r and omized , double‐blind , placebo‐controlled study of low‐level laser therapy ( LLLT ) in 90 subjects with chronic neck pain was conducted with the aim of determining the efficacy of 300 mW , 830 nm laser in the management of chronic neck pain . Subjects were r and omized to receive a course of 14 treatments over 7 weeks with either active or sham laser to tender areas in the neck . The primary outcome measure was change in a 10 cm Visual Analogue Scale ( VAS ) for pain . Secondary outcome measures included Short‐Form 36 Quality ‐of‐Life question naire ( SF‐36 ) , Northwick Park Neck Pain Question naire ( NPNQ ) , Neck Pain and Disability Scale ( NPAD ) , the McGill Pain Question naire ( MPQ ) and Self‐Assessed Improvement ( SAI ) in pain measured by VAS . Measurements were taken at baseline , at the end of 7 weeks ' treatment and 12 weeks from baseline . The mean VAS pain scores improved by 2.7 in the treated group and worsened by 0.3 in the control group ( difference 3.0 , 95 % CI 3.8–2.1 ) . Significant improvements were seen in the active group compared to placebo for SF‐36‐Physical Score ( SF36 PCS ) , NPNQ , NPAD , MPQVAS and SAI . The results of the SF‐36 – Mental Score ( SF36 MCS ) and other MPQ component scores ( afferent and sensory ) did not differ significantly between the two groups . Low‐level laser therapy ( LLLT ) , at the parameters used in this study , was efficacious in providing pain relief for patients with chronic neck pain over a period of 3 months Low-energy laser therapy has been applied in several rheumatoid and soft tissue disorders with varying rates of success . The objective of our study was to investigate the effect of laser therapy on cervical myofascial pain syndrome with a placebo-controlled double-blind prospect i ve study model . It was performed with a total of 53 patients ( 35 females and 18 males ) with cervical myofascial pain syndrome . In group 1 ( n=23 ) , GaAs laser treatment was applied over three trigger points bilaterally and also one point in the taut b and s in trapezius muscle bilaterally with a frequency of 1000 Hz for 2 min over each point once a day for 10 days during a period of 2 weeks . In group 2 ( n=25 ) , the same treatment protocol was given , but the laser instrument was switched off during applications . All patients in both groups were instructed to perform daily isometric exercises and stretching just short of pain for 2 weeks at home . Evaluations were performed just before treatment ( week 0 ) , immediately after ( week 2 ) , and 12 weeks later ( week 14 ) . Evaluation parameters included pain , algometric measurements , and cervical lateral flexion . Statistical analysis was done on data collected from three evaluation stages . The results were evaluated in 48 patients ( 32 females , 16 males ) . Week 2 and week 14 results showed significant improvement in all parameters for both groups . However , comparison of the percentage changes both immediately and 12 weeks after treatment did not show a significant difference relative to pretreatment values . In conclusion , the results of our study have not shown the superiority of GaAs laser therapy over placebo in the treatment of cervical myofascial pain syndrome , but we suggest that further studies on this topic be done using different laser types and dosages in larger patient population & 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 BACKGROUND AND OBJECTIVES A prospect i ve , double-blind , r and omized , and controlled trial was conducted in patients with chronic myofascial pain syndrome ( MPS ) in the neck to evaluate the effects of infrared low level 904 nm Gallium-Arsenide ( Ga-As ) laser therapy ( LLLT ) on clinical and quality of life ( QoL ) . STUDY DESIGN / PATIENTS AND METHODS The study group consisted of 60 MPS patients . Patients were r and omly assigned to two treatment groups : Group I ( actual laser ; 30 patients ) and Group II ( placebo laser ; 30 patients ) . LLLT continued daily for 2 weeks except weekends . Follow-up measures were evaluated at baseline , 2 , 3 , and 12 weeks . All patients were evaluated with respect to pain at rest , pain at movement , number of trigger points ( TP ) , the Neck Pain and Disability Visual Analog Scale ( NPAD ) , Beck depression Inventory ( BDI ) , and the Nottingham Health Profile ( NHP ) . RESULTS In active laser group , statistically significant improvements were detected in all outcome measures compared with baseline ( P < 0.01 ) while in the placebo laser group , significant improvements were detected in only pain score at rest at the 1 week later of the end of treatment . The score for self-assessed improvement of pain was significantly different between the active and placebo laser groups ( 63 vs. 19 % ) ( P < 0.01 ) . CONCLUSION This study revealed that short-period application of LLLT is effective in pain relief and in the improvement of functional ability and QoL in patients with MPS The efficacy of low-level laser therapy ( LLLT ) in myofascial pain syndrome ( MPS ) seems controversial . A prospect i ve , double-blind , r and omized controlled trial was conducted in patients with chronic MPS in the neck to evaluate the effects of low-level 830-nm gallium arsenide aluminum ( Ga – As – Al ) laser therapy . The study group consisted of 64 MPS patients . The patients were r and omly assigned into two groups . In group 1 ( n = 32 ) , Ga – As – Al laser treatment was applied over three trigger points bilaterally for 2 min over each point once a day for 15 days during a period of 3 weeks . In group 2 ( n = 32 ) , the same treatment protocol was given , but the laser instrument was switched off during applications . All patients in both groups performed daily isometric exercise and stretching exercises for cervical region . Parameters were measured at baseline and after 4 weeks . All patients were evaluated with respect to pain ( at rest , movement , and night ) and assessed by visual analog scale , measurement of active range of motion using an inclinometer and a goniometer , and the neck disability index . In both groups , statistically significant improvements were detected in all outcome measures compared with baseline ( p < 0.05 ) . However , no significant differences were obtained between the two groups ( p > 0.05 ) . In conclusion , although the laser therapy has no superiority over placebo groups in this study , we can not exclude the possibility of effectivity with another treatment regimen including different laser wavelengths and dosages ( different intensity and density and /or treatment interval ) Abstract : Pain is a major symptom in cervical osteoarthritis ( COA ) . Low-power laser ( LPL ) therapy has been cl aim ed to reduce pain in musculoskeletal pathologies , but there have been concerns about this point . The aim of this study was to evaluate the analgesic efficacy of LPL therapy and related functional changes in COA . Sixty patients between 20 and 65 years of age with clinical ly and radiologically diagnosed COA were included in the study . They were r and omised into two equal groups according to the therapies applied , either with LPL or placebo laser . Patients in each group were investigated blindly in terms of pain and pain-related physical findings , such as increased paravertebral muscle spasm , loss of lordosis and range of neck motion restriction before and after therapy . Functional improvements were also evaluated . Pain , paravertebral muscle spasm , lordosis angle , the range of neck motion and function were observed to improve significantly in the LPL group , but no improvement was found in the placebo group . LPL seems to be successful in relieving pain and improving function in osteoarthritic \n Output:\n " }, { "from": "agent", "value": "The benefit seen in the use of LLLT , although statistically significant , does not constitute the threshold of minimally important clinical difference" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: BACKGROUND The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen ( PSA ) testing remains uncertain . METHODS We compared active monitoring , radical prostatectomy , and external-beam radiotherapy for the treatment of clinical ly localized prostate cancer . Between 1999 and 2009 , a total of 82,429 men 50 to 69 years of age received a PSA test ; 2664 received a diagnosis of localized prostate cancer , and 1643 agreed to undergo r and omization to active monitoring ( 545 men ) , surgery ( 553 ) , or radiotherapy ( 545 ) . The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up . Secondary outcomes included the rates of disease progression , metastases , and all-cause deaths . RESULTS There were 17 prostate-cancer-specific deaths overall : 8 in the active-monitoring group ( 1.5 deaths per 1000 person-years ; 95 % confidence interval [ CI ] , 0.7 to 3.0 ) , 5 in the surgery group ( 0.9 per 1000 person-years ; 95 % CI , 0.4 to 2.2 ) , and 4 in the radiotherapy group ( 0.7 per 1000 person-years ; 95 % CI , 0.3 to 2.0 ) ; the difference among the groups was not significant ( P=0.48 for the overall comparison ) . In addition , no significant difference was seen among the groups in the number of deaths from any cause ( 169 deaths overall ; P=0.87 for the comparison among the three groups ) . Metastases developed in more men in the active-monitoring group ( 33 men ; 6.3 events per 1000 person-years ; 95 % CI , 4.5 to 8.8 ) than in the surgery group ( 13 men ; 2.4 per 1000 person-years ; 95 % CI , 1.4 to 4.2 ) or the radiotherapy group ( 16 men ; 3.0 per 1000 person-years ; 95 % CI , 1.9 to 4.9 ) ( P=0.004 for the overall comparison ) . Higher rates of disease progression were seen in the active-monitoring group ( 112 men ; 22.9 events per 1000 person-years ; 95 % CI , 19.0 to 27.5 ) than in the surgery group ( 46 men ; 8.9 events per 1000 person-years ; 95 % CI , 6.7 to 11.9 ) or the radiotherapy group ( 46 men ; 9.0 events per 1000 person-years ; 95 % CI , 6.7 to 12.0 ) ( P<0.001 for the overall comparison ) . CONCLUSIONS At a median of 10 years , prostate-cancer-specific mortality was low irrespective of the treatment assigned , with no significant difference among treatments . Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring . ( Funded by the National Institute for Health Research ; ProtecT Current Controlled Trials number , IS RCT N20141297 ; Clinical Trials.gov number , NCT02044172 . ) BACKGROUND The Prostate Cancer Research International Active Surveillance ( PRIAS ) study was initiated a decade ago to study the most optimal selection and follow-up of men on active surveillance ( AS ) . OBJECTIVE We report on 10 yr of follow-up of men on AS in the PRIAS study and evaluate if criteria used to recommend a switch to active treatment truly predict unfavorable outcome on subsequent radical prostatectomy ( RP ) . DESIGN , SETTING , AND PARTICIPANTS Men with low-risk prostate cancer were included and followed prospect ively on AS . Follow-up consisted of regular prostate-specific antigen ( PSA ) tests , digital rectal examinations , and biopsies . Men with Gleason > 3 + 3 , more than two positive biopsy cores , or stage higher than cT2 were advised to switch to active treatment ( until 2014 , a PSA doubling time [ PSA DT ] of 0 - 3 yr was also used ) . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Reclassification rates , treatment after discontinuation , and outcome on RP after discontinuing AS were reported . Regression analysis on the outcome of RP was used to evaluate the predictive value of criteria currently used to recommend a switch to active treatment . Kaplan-Meier and competing risk analysis were used to report discontinuation rates over time and long-term oncologic end points . RESULTS AND LIMITATIONS A total of 5302 men were included in PRIAS across 18 countries . Reclassification rates remained stable on all subsequent biopsies , with 22 - 33 % of men having either Gleason > 3 + 3 or more than two positive cores on any repeat biopsy . At 5 and 10 yr of follow-up , 52 % and 73 % of men , respectively , had discontinued AS , most of them because of protocol -based reclassification . A third of men undergoing subsequent RP had favorable pathologic tumor features ( Gleason 3 + 3 and pT2 ) . Of the criteria used to recommend a switch to active treatment , more than two positive cores and a PSA DT of 0 - 3 yr were not predictive of unfavorable pathologic outcome on RP . CONCLUSIONS A substantial group of men discontinued AS without subsequent unfavorable tumor features on RP ; therefore , we propose Gleason upgrading and cT3 as the only indicators for an immediate switch to active treatment . Surrogate indicators ( eg , more than two positive cores and a fast-rising PSA ) should not trigger immediate active treatment but rather further investigation to confirm the suspicion of higher risk disease . PATIENT SUMMARY We confirmed the safety of active surveillance as a treatment option for men with low-risk prostate cancer ; however , some changes could be made to the follow-up protocol to safely increase the number of men who remain on active surveillance OBJECTIVE To develop nomograms that predict the probability of overall prostate cancer ( PCa ) and clinical ly significant PCa ( Gleason ≥7 ) on magnetic resonance imaging (MRI)-targeted , and combined MRI-targeted and systematic , prostate biopsy . MATERIAL S AND METHODS From June 2012 to August 2014 , magnetic resonance imaging to ultrasound fusion-targeted prostate biopsy was performed on 464 men with suspicious regions identified on pre-biopsy 3 T MRI along with systematic 12 core biopsy . Logistic regression modeling was used to evaluate predictors of overall and clinical ly significant PCa , and corresponding nomograms were generated for men who were not previously biopsied or had 1 or more prior negative biopsies . Models were created with 70 % of a r and omly selected training sample and bias-corrected using bootstrap resampling . The models were then vali date d with the remaining 30 % testing sample pool . RESULTS A total of 459 patients were included for analysis ( median age 66 years , prostate-specific antigen [ PSA ] 5.2 ng/mL , prostate volume 49 cc ) . Independent predictors of PCa on targeted and systematic prostate biopsy were PSA density , age , and MRI suspicion score . PCa probability nomograms were generated for each cohort using the predictors . Bias-corrected areas under the receiver-operating characteristic curves for overall and clinical ly significant PCa detection were 0.82 ( 0.78 ) and 0.91 ( 0.84 ) for men without prior biopsy and 0.76 ( 0.65 ) and 0.86 ( 0.87 ) for men with a prior negative biopsy in the training ( testing ) sample s. CONCLUSION PSA density , age , and MRI suspicion score predict PCa on combined MRI-targeted and systematic biopsy . Our generated nomograms demonstrate high diagnostic accuracy and may further aid in the decision to perform biopsy in men with clinical suspicion of PCa BACKGROUND Prostate Imaging-Reporting and Data System v. 2 ( PI-RADSv2 ) provides st and ardized nomenclature for interpretation of prostate multiparametric MRI ( mpMRI ) . Inclusion of additional features for categorization may provide benefit to stratification of disease . PURPOSE To prospect ively compare PI-RADSv2 to a qualitative in-house system for detecting prostate cancer on mpMRI . STUDY TYPE Prospect i ve . POPULATION In all , 338 patients who underwent mpMRI May 2015-May 2016 , with subsequent MRI/transrectal ultrasound fusion-guided biopsy . FIELD STRENGTH 3 T mpMRI ( T2 W , diffusion-weighted [ DW ] , apparent diffusion coefficient [ ADC ] map , b-2000 DWI acquisition , and dynamic contrast-enhanced [ DCE ] MRI ) . ASSESSMENT One genitourinary radiologist prospect ively read mpMRIs using both in-house and PI-RADSv2 5-category systems . STATISTICAL TEST In lesion-based analysis , overall and clinical ly significant ( CS ) tumor detection rates ( TDR ) were calculated for all PI-RADSv2 and in-house categories . The ability of each scoring system to detect cancer was assessed by area under receiver operator characteristic curve ( AUC ) . Within each PI-RADSv2 category , lesions were further stratified by their in-house categories to determine if TDRs can be increased by combining features of both systems . RESULTS In 338 patients ( median prostate-specific antigen [ PSA ] 6.5 [ 0.6 - 113.6 ] ng/mL ; age 64 [ 44 - 84 ] years ) , 733 lesions were identified ( 47 % tumor-positive ) . Predictive abilities of both systems were comparable for all ( AUC 76 - 78 % ) and CS cancers ( AUCs 79 % ) . The in-house system had higher overall and CS TDRs than PI-RADSv2 for categories 3 and 4 ( P < 0.01 for both ) , with the greatest difference between the scoring systems seen in lesions scored category 4 ( CS TDRs : in-house 65 % , PI-RADSv2 22.1 % ) . For lesions categorized as PI-RADSv2 = 4 , characterization of suspicious/indeterminate extraprostatic extension ( EPE ) and equivocal findings across all mpMRI sequences contributed to significantly different TDRs for both systems ( TDR range 19 - 75 % , P < 0.05 ) . DATA CONCLUSION PI-RADSv2 behaves similarly to an existing vali date d system that relies on the number of sequences on which a lesion is seen . This prospect i ve evaluation suggests that sequence positivity and suspicion of EPE can enhance PI-RADSv2 category 4 cancer detection . LEVEL OF EVIDENCE 1 Technical Efficacy : Stage 3 J. Magn . Reson . Imaging 2018;47:1326 - 1335 Purpose : We sought to determine whether saturation of the index lesion during magnetic resonance imaging‐transrectal ultrasound fusion guided biopsy would decrease the rate of pathological upgrading from biopsy to radical prostatectomy . Material s and Methods : We analyzed a prospect ively maintained , single institution data base for patients who underwent fusion and systematic biopsy followed by radical prostatectomy in 2010 to 2016 . Index lesion was defined as the lesion with largest diameter on T2‐weighted magnetic resonance imaging . In patients with a saturated index lesion transrectal fusion biopsy targets were obtained at 6 mm intervals along the long axis of the index lesion . In patients with a nonsaturated index lesion only 1 target was obtained from the lesion . Gleason 6 , 7 and 8‐10 were defined as low , intermediate and high risk , respectively . Results : Included in the study were 208 consecutive patients , including 86 with a saturated and 122 with a nonsaturated lesion . Median patient age was 62.0 years ( IQR 10.0 ) and median prostate specific antigen was 7.1 ng/ml ( IQR 8.0 ) . The median number of biopsy cores per index lesion was higher in the saturated lesion group ( 4 vs 2 , p < 0.001 ) . The risk category up grade rate from systematic only , fusion only , and combined fusion and systematic biopsy results to prostatectomy was 40.9 % , 23.6 % and 13.8 % , respectively . The risk category up grade from combined fusion and systematic biopsy results was lower in the saturated than in the nonsaturated lesion group ( 7 % vs 18 % , p = 0.021 ) . There was no difference in the up grade rate based on systematic biopsy between the 2 groups . However , fusion biopsy results were significantly less up grade d in the saturated lesion group ( Gleason up grade 20.9 % vs 36.9 % , p = 0.014 and risk category up grade 14 % vs 30.3 % , p = 0.006 ) . Conclusions : Our results demonstrate that saturation of the index lesion significantly decreases the risk of upgrading on radical prostatectomy by minimizing the impact of tumor heterogeneity Purpose To vali date the dominant pulse sequence paradigm and limited role of dynamic contrast material -enhanced magnetic resonance ( MR ) imaging in the Prostate Imaging Reporting and Data System ( PI \n Output:\n " }, { "from": "agent", "value": "EVIDENCE SYNTHESIS It has been shown that the test performance of PI-RADS v2 in research and clinical practice retains higher accuracy over systematic transrectal ultrasound ( TRUS ) biopsies for PCa diagnosis .\nPI-RADS v2 fails to detect all cancers but does detect the majority of tumors capable of causing patient harm , which should not be missed .\nTest performance depends on the definition and prevalence of clinical ly significant disease .\nIt has been shown that the test performance of PI-RADS v2 in research and clinical practice is improved , retaining higher accuracy over systematic TRUS biopsies for PCa diagnosis .\nPATIENT SUMMARY Multiparametric magnetic resonance imaging ( MRI ) and MRI-directed biopsies using the Prostate Imaging-Reporting and Data System improves the detection of prostate cancers likely to cause harm , and at the same time decreases the detection of disease that does not lead to harms if left untreated ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: The effectiveness of cabbage leaf extract was compared with that of a placebo in treating breast engorgement in lactating women . In a double-blind experiment with a pretest/posttest design , 21 participants received a cream containing cabbage leaf extract , while 18 received placebo cream . The placebo group received equal relief to the treated group , with the two groups showing no difference on all outcome measures . However , mothers perceived both creams to be effective in relieving discomfort . Feeding had a greater effect than the application of cream on relieving discomfort and decreasing tissue hardness . It is therefore recommended that lactation consultants encourage mothers to breastfeed if possible to relieve the discomfort of breast engorgement We evaluated an anti-inflammatory enzyme drug Danzen ( Serrapeptase : Takeda Chemical Industries , Ltd. ) on 70 patients complaining of breast engorgement . These patients were r and omly divided into 2 groups , a treatment group and a placebo group . A single observer , unaware of the group the patients were in , assessed the severity of each of the symptoms and signs of breast engorgement before treatment was commenced , and daily for 3 days , during which therapy was administered . Danzen was noted to be superior to placebo for improvement of breast pain , breast swelling and in duration and while 85.7 % of the patients receiving Danzen had \" Moderate to Marked \" improvement , only 60.0 % of the patients receiving placebo had a similar degree of improvement . \" Marked \" improvement was found in 22.9 % of the treatment group and 2.9 % of the placebo group . These differences were statistically significant ( P less than 0.05 ) . No adverse reactions were reported with the use of Danzen . Danzen is a safe and effective method for the treatment of breast engorgement The aim of this study was to test the efficacy of thermal ultrasound therapy as a treatment for severe post partum breast engorgement . A r and omised double-blind , placebo-controlled trial was conducted on 197 breasts . Two ultrasound machines of identical appearance were used . One was working normally , the other had the crystal replaced with a resistor producing surface heat only . Assessment of effectiveness was subjective , using visual analogue scales for pain and hardness , and objective , using tonometry . Results indicate that both the true and sham machines were effective in reducing subjectively perceived pain and hardness . However , the results of this study show that the effect can not be attributed to the ultrasound component This study compared the effectiveness of chilled green cabbage leaves and chilled gelpaks in reducing breast engorgement in postpartum mothers . Thirtyfour lactating women with breast engorgement used chilled cabbage leaves on one breast and chilled gelpaks on the other for up to eight hours . Their pain levels were established pre-treatment and compared post-treatment for both conditions . There was no difference in the post-treatment ratings for the two treatments . Mothers reported a statistically significant drop in pain with both treatments ; 68 percent obtained relief within one to two hours . The majority of mothers preferred the cabbage leaves A r and omized , controlled trial was conducted to evaluate the effect of cabbage leaves on mothers ' perceptions of breast engorgement and the influence of this treatment on breastfeeding practice s. The subjects , 120 breastfeeding women 72 hours postpartum , were r and omly allocated to an experimental group who received application of cabbage leaves to their breasts , or to a control group who received routine care . The experimental group tended to report less breast engorgement , but this trend was not statistically significant . At six weeks , women who received the cabbage leaf application were more likely to be breastfeeding exclusively , 76 and 58 percent ( 35/46 vs 29/50 ; P = 0.09 ) , and their mean duration of exclusive breastfeeding was longer ( 36 vs 30 days ; P = 0.04 ) . The greater breastfeeding success in the experimental group may have been due to some beneficial effect of cabbage leaf application , or may have been secondary to reassurance and improved confidence and self-esteem in these mothers This study compared the effectiveness of chilled and room temperature green cabbage leaves in reducing the discomfort of breast engorgement in postpartum mothers . Twenty-eight lactating women with breast engorgement used chilled cabbage leaves on one breast and room-temperature cabbage leaves on the other for a two-hour period . Pre-treatment pain levels were compared with post-treatment levels for both conditions . There was no difference in the post-treatment ratings for the two treatments ; mothers reported significantly less pain with both treatments . We concluded that it is not necessary to chill cabbage leaves before use \n Output:\n " }, { "from": "agent", "value": "Ultrasound treatment and placebo were equally effective .\nOxytocin and cold packs had no demonstrable effect on engorgement symptoms .\nREVIEW ER 'S CONCLUSIONS Cabbage leaves and gel packs were equally effective in the treatment of engorgement .\nSince both cabbage extract and placebo cream were equally effective , the alleviation in symptoms may be brought about by other factors , such as breast massage .\nUltrasound treatment is equally effective with or without the ultra-wave emitting crystal , therefore its effectiveness is more likely to be due to the effect of radiant heat or massage .\nPharmacologically , oxytocin was not an effective engorgement treatment while Danzen and bromelain/trypsin complex significantly improved the symptoms of engorgement ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: AIM To determine the long-term efficacy of autologous bone marrow mononuclear cells ( BM-MNCs ) transplantation in terms of improving liver function and reducing complications in patients with decompensated cirrhosis . METHODS A total of 47 in patients with decompensated liver cirrhosis were enrolled in this trial , including 32 patients undergoing a single BM-MNCs transplantation plus routine medical treatment , and 15 patients receiving medical treatment only as controls . Forty-three of 47 patients were infected with hepatitis B virus . Bone marrow of 80 - 100 mL was obtained from each patient and the BM-MNCs suspension was transfused into the liver via the hepatic artery . The efficacy of BM-MNCs transplantation was monitored during a 24-mo follow-up period . RESULTS Liver function parameters in the two groups were observed at 1 mo after BM-MNCs transfusion . Prealbumin level was 118.3 ± 25.3 mg/L vs 101.4 ± 28.7 mg/L ( P = 0.047 ) ; albumin level was 33.5 ± 3.6 g/L vs 30.3 ± 2.2 g/L ( P = 0.002 ) ; total bilirubin 36.9 ± 9.7 mmol/L vs 45.6 ± 19.9 mmol/L ( P = 0.048 ) ; prothrombin time 14.4 ± 2.3 s vs 15.9 ± 2.8 s ( P = 0.046 ) ; prothrombin activity 84.3 % ± 14.3 % vs 74.4 % ± 17.8 % ( P = 0.046 ) ; fibrinogen 2.28 ± 0.53 g/L vs 1.89 ± 0.44 g/L ( P = 0.017 ) ; and platelet count 74.5 ± 15.7 × 10(9)/L vs 63.3 ± 15.7 × 10(9)/L ( P = 0.027 ) in the treatment group and control group , respectively . Differences were statistically significant . The efficacy of BM-MNCs transplantation lasted 3 - 12 mo as compared with the control group . Serious complications such as hepatic encephalopathy and spontaneous bacterial peritonitis were also significantly reduced in BM-MNCs transfused patients compared with the controls . However , these improvements disappeared 24 mo after transplantation . CONCLUSION BM-MNCs transplantation is safe and effective in patients with decompensated cirrhosis . It also decreases the incidence of serious complications Summary Background More than half of patients with multiple sclerosis have progressive disease characterised by accumulating disability . The absence of treatments for progressive multiple sclerosis represents a major unmet clinical need . On the basis of evidence that mesenchymal stem cells have a beneficial effect in acute and chronic animal models of multiple sclerosis , we aim ed to assess the safety and efficacy of these cells as a potential neuroprotective treatment for secondary progressive multiple sclerosis . Methods Patients with secondary progressive multiple sclerosis involving the visual pathways ( exp and ed disability status score 5·5–6·5 ) were recruited from the East Anglia and north London regions of the UK . Participants received intravenous infusion of autologous bone-marrow-derived mesenchymal stem cells in this open-label study . Our primary objective was to assess feasibility and safety ; we compared adverse events from up to 20 months before treatment until up to 10 months after the infusion . As a secondary objective , we chose efficacy outcomes to assess the anterior visual pathway as a model of wider disease . Masked endpoint analyses was used for electrophysiological and selected imaging outcomes . We used piecewise linear mixed models to assess the change in gradients over time at the point of intervention . This trial is registered with Clinical Trials.gov , number NCT00395200 . Findings We isolated , exp and ed , characterised , and administered mesenchymal stem cells in ten patients . The mean dose was 1·6 × 106 cells per kg bodyweight ( range 1·1–2·0 ) . One patient developed a transient rash shortly after treatment ; two patients had self-limiting bacterial infections 3–4 weeks after treatment . We did not identify any serious adverse events . We noted improvement after treatment in visual acuity ( difference in monthly rates of change −0·02 logMAR units , 95 % CI −0·03 to −0·01 ; p=0·003 ) and visual evoked response latency ( −1·33 ms , −2·44 to −0·21 ; p=0·020 ) , with an increase in optic nerve area ( difference in monthly rates of change 0·13 mm2 , 0·04 to 0·22 ; p=0·006 ) . We did not identify any significant effects on colour vision , visual fields , macular volume , retinal nerve fibre layer thickness , or optic nerve magnetisation transfer ratio . Interpretation Autologous mesenchymal stem cells were safely given to patients with secondary progressive multiple sclerosis in our study . The evidence of structural , functional , and physiological improvement after treatment in some visual endpoints is suggestive of neuroprotection . Funding Medical Research Council , Multiple Sclerosis Society of Great Britain and Northern Irel and , Evelyn Trust , NHS National Institute for Health Research , Cambridge and UCLH Biomedical Research Centres , Wellcome Trust , Raymond and Beverly Sackler Foundation , and Sir David and Isobel Walker Trust Background : Chronic hepatitis B virus ( HBV ) infection may eventually lead to decompensated liver cirrhosis , which is a terminal illness . Objectives : The aim of this study was to investigate the therapeutic efficacy of autologous peripheral blood stem cell ( APBSC ) transplantation to improve portal vein hemodynamics in patients with HBV-related decompensated cirrhosis . Patients and Methods : This prospect i ve study included 68 hospitalized patients who were diagnosed with HBV-related decompensated cirrhosis . These patients were divided into two groups : the transplantation group included 33 patients , while the control group included 35 . Both groups received conventional medical treatment simultaneously , and APBSC transplantation was performed on the patients in the transplantation group . We evaluated the effects of APBSC transplantation on postoperative liver function using the following indices : total bilirubin , serum prothrombin and albumin , spleen size , and portal vein hemodynamics . Postoperatively , all of the patients were followed up at 24 , 36 , and 48 weeks . Results : The transplantation group had no serious reactions . Compared with the control group , albumin and prothrombin activity in the transplantation group was significantly improved at 24 , 36 , and 48 weeks after the procedure , and spleen length and portal vein diameter were substantially reduced at 48 weeks . The velocity of peak portal vein blood flow and mean maximum portal vein blood flow were greatly increased in the APBSC transplantation group at 36 and 48 weeks , respectively ; however , there was also decreased portal vein diameter , which reduced portal vein pressure in patients with HBV-related decompensated cirrhosis . Conclusions : APBSC transplantation greatly benefits HBV-linked decompensated cirrhosis patients and should be recommended in clinical practice Objectives Counseling patients with acute-on-chronic hepatitis B liver failure ( ACHBLF ) on their individual risk of short-term mortality is challenging . This study aim ed to develop a conditional survival estimate ( CSE ) for predicting individualized mortality risk in ACHBLF patients . Methods We performed a large prospect i ve cohort study of 278 ACHBLF patients from December 2010 to December 2013 at three participating medical centers . The Kaplan-Meier method was used to calculate the cumulative overall survival ( OS ) . Cox proportional hazard regression models were used to analyze the risk factors associated with OS . 4-week CSE at “ X ” week after diagnostic established were calculated as CS4 = OS(X+4)/OS(X ) . Results The actual OS at 2 , 4 , 6 , 8 , 12 weeks were 80.5 % , 71.8 % , 69.3 % , 66.0 % and 63.7 % , respectively . Using CSE , the probability of surviving an additional 4 weeks , given that the patient had survived for 1 , 3 , 5 , 7 , 9 weeks was 74 % , 86 % , 92 % , 93 % , 97 % , respectively . Patients with worse prognostic feathers , including MELD > 25 , Child grade C , age > 45 , HE , INR > 2.5 , demonstrated the greatest increase in CSE over time , when compared with the “ favorable ” one ( Δ36 % vs. Δ10 % ; Δ28 % vs. Δ16 % ; Δ29 % vs. Δ15 % ; Δ60 % vs. Δ12 % ; Δ33 % vs. Δ12 % ; all P < 0.001 ; respectively ) . Conclusions This easy-to-use CSE can accurately predict the changing probability of survival over time . It may facilitate risk communication between patients and physicians Mortality from hepatitis B virus (HBV)-related acute-on-chronic liver failure ( ACLF ) is high due to limited treatment options . Pre clinical and clinical investigations have proved that treatment with mesenchymal stromal cells ( MSCs ) is beneficial for recovery from liver injury . We hypothesized that the outcome of HBV-related ACLF would be improved by MSC treatment . From 2010 to 2013 , 110 patients with HBV-related ACLF were enrolled in this open-label , nonblinded r and omized controlled study . The control group ( n = 54 ) was treated with st and ard medical therapy ( SMT ) only . The experimental group ( n = 56 ) was infused weekly for 4 weeks with 1.0 to 10 × 105 cells/kg allogeneic bone marrow-derived MSCs and then followed for 24 weeks . The cumulated survival rate of the MSC group was 73.2 % ( 95 % confidence interval 61.6%-84.8 % ) versus 55.6 % ( 95 % confidence interval 42.3%-68.9 % ) for the SMT group ( P = 0.03 ) . There were no infusion-related side effects , but fever was more frequent in MSC compared to SMT patients during weeks 5 - 24 of follow-up . No carcinoma occurred in any trial patient in either group . Compared with the control group , allogeneic bone marrow-derived MSC treatment markedly improved clinical laboratory measurements , including serum total bilirubin and Model for End-Stage Liver Disease scores . The incidence of severe infection in the MSC group was much lower than that in the SMT group ( 16.1 % versus 33.3 % , P = 0.04 ) . Mortality from multiple organ failure and severe infection was higher in the SMT group than in the MSC group ( 37.0 % versus 17.9 % , P = 0.02 ) . CONCLUSION Peripheral infusion of allogeneic bone marrow-derived MSCs is safe and convenient for patients with HBV-related ACLF and significantly increases the 24-week survival rate by improving liver function and decreasing the incidence of severe infections . ( Hepatology 2017;66:209 - 219 ) UNLABELLED The present study assessed the effects of intraportal infusions of autologous bone marrow-derived mononuclear cells ( MNCs ) and /or CD133 + cells on liver function in patients with decompensated cirrhosis . We r and omly assigned 27 eligible patients to a placebo , MNCs , and /or CD133 + cells . Cell infusions were performed at baseline and month 3 . We considered the absolute changes in the Model for End-Stage Liver Disease ( MELD ) scores at months 3 and 6 after infusion as the primary outcome . The participants and those who assessed the outcomes were unaware of the treatment intervention assignments . After 6 months , 9 patients were excluded because of liver transplantation ( n=3 ) , hepatocellular carcinoma ( n=1 ) , loss to follow-up ( n=3 ) , and death ( n=2 ) . The final analysis included 4 patients from the CD133 + group , 8 from the MNC group , and 6 from the placebo group . No improvement was seen in the MELD score at month 6 using either CD133 + cells or MNC infusions compared with placebo . However , at month 3 after infusion , a trend was seen toward a higher mean absolute change in the MELD score in patients who had received CD133 + cells compared with placebo ( -2.00±1.87 vs. -0.13±1.46 ; p=.08 ) . No significant adverse events occurred in the present study . A transient improvement in the MELD score was observed in subjects treated with CD133 + cells but not in the MNC or placebo group . Although the study was not powered to make definitive conclusions , the data justify further study of CD133 + therapy in cirrhotic patients . SIGNIFICANCE Cell therapy is a new approach in liver disease . Several clinical experiments have been reported on the safety of bone marrow-derived stem cells to treat liver disorders . However , the effectiveness of these approaches in the long-term follow-ups of patients initiated controversial discussion \n Output:\n " }, { "from": "agent", "value": "Conclusion This study suggests that the clinical outcomes of stem cell therapy were satisfied in patients with ACLF in the short-term .\nMSCs may be better than BM-MNCs in the stem cells transplantation of ACLF ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Background To improve continuity of care at hospital admission and discharge and to decrease medication errors pharmaceutical care programs are developed . This study aims to determine the cost-effectiveness of the COACH program in comparison with usual care from a societal perspective . Methods A controlled clinical trial was performed at the Internal Medicine department of a general teaching hospital . All admitted patients using at least one prescription drug were included . The COACH program consisted of medication reconciliation , patient counselling at discharge , and communication to healthcare providers in primary care . The primary outcome was the proportion of patients with an unplanned rehospitalisation within three months after discharge . Also , the number of quality -adjusted life-years ( QALYs ) was assessed . Cost data were collected using cost diaries . Uncertainty surrounding cost differences and incremental cost-effectiveness ratios between the groups was estimated by bootstrapping . Results In the COACH program , 168 patients were included and in usual care 151 patients . There was no significant difference in the proportion of patients with unplanned rehospitalisations ( mean difference 0.17 % , 95 % CI -8.85;8.51 ) , and in QALYs ( mean difference -0.0085 , 95 % CI -0.0170;0.0001 ) . Total costs for the COACH program were non-significantly lower than usual care ( -€1160 , 95 % CI -3168;847 ) . Cost-effectiveness planes showed that the program was not cost-effective compared with usual care for unplanned rehospitalisations and QALYs gained . Conclusion The COACH program was not cost-effective in comparison with usual care . Future studies should focus on high risk patients and include other outcomes ( e.g. adverse drug events ) as this may increase the chances of a cost-effective intervention . Dutch trial register & NA ; A critical analysis of the research on clinical pharmacy services with regards to study characteristics has not been undertaken since 1998 . However , several meta‐analyses have been conducted to demonstrate the impact of pharmacists ' interventions in specific medical conditions . These meta‐analyses present high heterogeneity in part because the interventions are poorly and inconsistently described in primary studies . The aim of this article is to present the characteristics of r and omized control trials ( RCTs ) that assess clinical pharmacy services to identify areas of improvement in future pharmacy practice research studies . Different emphasis of research across geographic regions of the world were also examined . During these 40 years , 520 articles reporting 439 RCTs assessing clinical pharmacy services were published . Of the 439 studies , 77.7 % ( n = 341 ) were published in the year 2000 or thereafter , 41.46 % ( n = 182 ) were conducted in the US , 27.56 % ( n = 121 ) in Europe , and 30.98 % ( n = 136 ) in the rest of the world . Studies in pharmacy practice have improved in terms of design , with an increase in the number of published RCTs after 2000 . However , the small sample size of RCTs is still an issue . After 2000 , a significantly higher proportion of studies were conducted in community pharmacy , targeting specific medical conditions , and with a higher number of patients r and omized to the intervention group . Conversely , a significantly smaller proportion of studies were conducted in the hospital and targeted a single recipient after 2000 . Studies conducted in the US had significantly more intervention arms , focused mostly on a specific medical condition , and were performed in primary care . Different health care systems ' organization and policies may influence clinical pharmacy services research across countries 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 BACKGROUND Hospitalization and subsequent discharge home often involve discontinuity of care , multiple changes in medication regimens , and inadequate patient education , which can lead to adverse drug events ( ADEs ) and avoidable health care utilization . Our objectives were to identify drug-related problems during and after hospitalization and to determine the effect of patient counseling and follow-up by pharmacists on preventable ADEs . METHODS We conducted a r and omized trial of 178 patients being discharged home from the general medicine service at a large teaching hospital . Patients in the intervention group received pharmacist counseling at discharge and a follow-up telephone call 3 to 5 days later . Interventions focused on clarifying medication regimens ; review ing indications , directions , and potential side effects of medications ; screening for barriers to adherence and early side effects ; and providing patient counseling and /or physician feedback when appropriate . The primary outcome was rate of preventable ADEs . RESULTS Pharmacists observed the following drug-related problems in the intervention group : unexplained discrepancies between patients ' preadmission medication regimens and discharge medication orders in 49 % of patients , unexplained discrepancies between discharge medication lists and postdischarge regimens in 29 % of patients , and medication nonadherence in 23 % . Comparing trial outcomes 30 days after discharge , preventable ADEs were detected in 11 % of patients in the control group and 1 % of patients in the intervention group ( P = .01 ) . No differences were found between groups in total ADEs or total health care utilization . CONCLUSIONS Pharmacist medication review , patient counseling , and telephone follow-up were associated with a lower rate of preventable ADEs 30 days after hospital discharge . Medication discrepancies before and after discharge were common targets of intervention OBJECTIVES : This study aim ed to evaluate the impact of pharmacist-provided discharge counseling on mortality rate , hospital readmissions , emergency department visits , and medication adherence at 30 days post discharge . METHODS : This r and omized controlled trial was approved by the local ethics committee and included patients aged 18 years or older admitted to the cardiology ward of a Brazilian tertiary hospital . The intervention group received a pharmacist-led medication counseling session at discharge and a telephone follow-up three and 15 days after discharge . The outcomes included the number of deaths , hospital readmissions , emergency department visits , and medication adherence . All outcomes were evaluated during a pharmacist-led ambulatory consultation performed 30 days after discharge . RESULTS : Of 133 patients , 104 were included in the analysis ( 51 and 53 in the intervention and control groups , respectively ) . The intervention group had a lower overall readmission rate , number of emergency department visits , and mortality rate , but the differences were not statistically significant ( p>0.05 ) . However , the intervention group had a significantly lower readmission rate related to heart disease ( 0 % vs. 11.3 % , p=0.027 ) , despite the small sample size . Furthermore , medication counseling contributed significantly to improved medication adherence according to three different tools ( p<0.05 ) . CONCLUSIONS : Pharmacist-provided discharge medication counseling result ed in better medication adherence scores and a lower incidence of cardiovascular-associated hospital readmissions , thus representing a useful service for cardiology patients Importance Hospital readmissions are common among patients receiving multiple medications , with considerable costs to the patients and society . Objective To determine whether a multifaceted pharmacist intervention based on medication review , patient interview , and follow-up can reduce the number of readmissions and emergency department ( ED ) visits . Design , Setting , and Participants This r and omized clinical multicenter study ( Odense Pharmacist Trial Investigating Medication Interventions at Sector Transfer [ OPTIMIST ] ) enrolled patients from September 1 , 2013 , through April 23 , 2015 , with a follow-up of 6 months completed on October 31 , 2015 . Consecutive medical patients in an acute admission ward who were 18 years or older and who used 5 or more medications were invited to participate . Of 1873 patients invited to participate , 1499 ( 80.0 % ) accepted . The medication review and patient interview were conducted in the hospital and followed up in collaboration with primary care . Analysis was based on intention to treat . Interventions The patients were r and omized into 3 groups receiving usual care ( no intervention ) , a basic intervention ( medication review ) , and an extended intervention ( medication review , 3 motivational interviews , and follow-up with the primary care physician , pharmacy , and nursing home ) . Main Outcomes and Measures The prespecified primary outcomes were readmission within 30 or 180 days and ED visits within 180 days . The primary composite end point was readmission or an ED visit within 180 days . Secondary outcomes were drug-related readmissions within 30 and 180 days after inclusion , and all-cause mortality and drug-related mortality . Results A total of 1467 patients ( 679 men [ 46.3 % ] and 788 women [ 53.7 % ] ; median age , 72 years ; interquartile range , 63 - 80 years ) were part of the primary analysis , including 498 r and omized to usual care , 493 r and omized to the basic intervention , and 476 r and omized to the extended intervention . The extended intervention had a significant effect on the numbers of patients who were readmitted within 30 days ( hazard ratio [ HR ] , 0.62 ; 95 % CI , 0.46 - 0.84 ) or within 180 days ( HR , 0.75 ; 95 % CI , 0.62 - 0.90 ) after inclusion and on the number of patients who experienced the primary composite end point ( HR , 0.77 ; 95 % CI , 0.64 - 0.93 ) . The study showed a nonsignificant reduction in drug-related readmissions within 30 days ( HR , 0.65 ; 95 % CI , 0.39 - 1.09 ) and within 180 days ( HR , 0.80 ; 95 % CI , 0.59 - 1.08 ) after inclusion and in deaths ( HR , 0.83 ; 95 % CI , 0.22 - 3.11 ) . The number needed to treat to achieve the primary composite outcome for the extended intervention ( vs usual care ) was 12 . Conclusions and Relevance A multifaceted clinical pharmacist intervention may reduce the number of ED visits and hospital readmissions . Trial Registration clinical trials.gov Identifier : 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 \n Output:\n " }, { "from": "agent", "value": "Insufficient evidence exists regarding the effect of pharmacist-led discharge counseling on hospital readmission and emergency department visits ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: BACKGROUND Multiple groups have reported on the use of repetitive transcranial magnetic stimulation ( rTMS ) in treatment-resistant major depression . The purpose of this study is to assess the efficacy of rTMS in unmedicated , treatment-resistant patients who meet criteria for major depression . METHODS Depressed subjects , who had failed to respond to a median of four treatment trials , were assigned in a r and omized double-blind manner to receive either active ( n = 10 ; 20 2-sec trains of 20 Hz stimulation with 58-sec intervals ; delivered at 80 % motor threshold with the figure-of-eight coil positioned over the left dorsolateral prefrontal cortex ) or sham ( n = 10 ; similar conditions with the coil elevated and angled 45 degrees tangentially to the scalp ) rTMS . These sequences were applied during 10 consecutive weekdays . Continuous electroencephalogram sampling and daily motor threshold determinations were also obtained . RESULTS The group mean 25-item Hamilton Depression Rating Scale ( HDRS ) score was 37.2 ( + /- 2.0 SEM ) points . Adjusted mean decreases in HDRS scores were 14.0 ( + /- 3.7 ) and 0.2 ( + /- 4.1 ) points for the active and control groups , respectively ( p < .05 ) . One of 10 subjects receiving active treatment demonstrated a robust response ( i.e. , HDRS decreased from 47 to 7 points ) ; three other patients demonstrated 40 - 45 % decreases in HDRS scores . No patients receiving sham treatment demonstrated partial or full responses . CONCLUSIONS A 2-week course of active rTMS result ed in statistically significant but clinical ly modest reductions of depressive symptoms , as compared to sham rTMS in a population characterized by treatment resistance BACKGROUND The role of high-frequency rTMS over the left cortex as an add-on strategy in the treatment of major depression is still uncertain even in patients resistant to pharmacotherapy . We had planned a large sham TMS controlled study in the acute phase with a placebo-controlled relapse-prevention phase with escitalopram . However , because a recent meta- analysis showed only a small effect size of rTMS over sham TMS in the acute treatment phase of depressed patients , we decided to make an interim analysis . METHOD In patients with medication-resistant major depression we administered in a r and omised trial 15 sessions of sham-controlled rTMS over three weeks in combination with 20 mg escitalopram daily . After the last rTMS , the patients were followed for another 9 weeks on 20 mg escitalopram daily . The antidepressant effect was measured by the HAM-D(6 ) as primary outcome scale . RESULTS A total of 45 patients with complete data were r and omised so that 23 patients received sham TMS and 22 patients received active , high-frequency rTMS over the left cortex . Over the 3 weeks , the active rTMS treatment was superior to sham TMS with effect sizes on the HAM-D(6 ) above 0.70 , which indicates not only a statistically but also a clinical ly significant effect . The patients had typically been through two failed antidepressant treatment attempts with non-tricyclics before inclusion in the study . Both the rTMS and escitalopram were well-tolerated . CONCLUSION High-frequency rTMS over the left cortex is an add-on strategy of clinical significance in combination with escitalopram in patients with major depression resistant to non-tricyclic antidepressants Rapid transcranial magnetic stimulation ( rTMS ) applied to the left dorsal lateral frontal cortex has been shown to produce antidepressant effects . Older depressed patients , however , in one study showed a lower response rate than younger patients . The current study examined treatment response in 20 depressed , treatment-refractory patients ( mean age 60.7 + /- 9.8 years ) given five sessions of rTMS at 20 Hz for 2 seconds over 20 trains at 80 % of motor threshold or identical placebo stimulation , after patients had been withdrawn from their antidepressants . There were no significant differences in Hamilton Depression Scale scores either before or after treatment at 7 days ' follow-up . There were three responders to active treatment and three to sham treatment and responders had significantly greater frontal lobe volume than nonresponders ( p = .03 ) . These findings suggest that the stimulation parameters used in this study were probably insufficient to produce treatment response and that frontal atrophy may interfere with the effectiveness of rTMS We conducted a prospect i ve , r and omized , sham-controlled , double blind , parallel group study of right or left pre-frontal rTMS in 48 subjects with medication-resistant depression . Two thous and ( 50x8-s trains of 5Hz ) stimuli at MEP threshold were delivered each weekday for 2weeks . We employed a sham coil and simultaneous electrical stimulation of the scalp to simulate rTMS . Mean ( + /-S.D. ) reductions in the HAMD-24 from baseline to 3-months were not significantly different between rTMS and sham treatment groups . However , right cranial stimulation ( sham or rTMS ) was significantly more effective than left cranial stimulation ( sham or rTMS ) ( P=0.012 ) . Mean ( + /-S.D. ) reductions in the HAMD from baseline to 3 months were : left : 28.1 ( + /-5.36 ) to 19.2 ( + /-11.2 ) ; and right 27.2 ( + /-4.2 ) to 11.5 ( + /-9.4 ) . Left rTMS achieved a reduction in HAMD 9.5 points greater than that achieved by left sham , a benefit greater than that reported in a recent multi-center Phase III trial of rTMS ( O'Reardon et al. , 2007 ) , albeit not statistically significant . These results suggest that somatosensory stimuli that repeatedly engage the left hemisphere may be important to the achievement of therapeutic effect OBJECTIVE A substantive body of research has demonstrated the efficacy of repetitive transcranial magnetic stimulation treatment ( rTMS ) in patients with depression . However , the parameters needed to optimize therapeutic efficacy remain unclear . The aim of this study was to investigate whether there is an advantage in efficacy of sequential bilateral rTMS compared to st and ard high-frequency left sided rTMS . METHOD Sixty seven patients with treatment resistant depression were included in a r and omised double-blind sham controlled trial of sequential bilateral rTMS compared to st and ard high-frequency left sided rTMS and sham rTMS over a three-week period . The study also included a further three week comparison of the two active treatment conditions . The primary outcome variable was scores on the 17-item Hamilton Depression Rating Scale ( HAMD ) . RESULTS In the three-week double-blind phase of the trial there was a greater antidepressant response to unilateral left sided rTMS compared with sham or bilateral rTMS . Across the full six weeks of active rTMS , there was also a consistent pattern of improved response in unilateral left compared to bilateral treatment . Response rates were low in both active groups . CONCLUSIONS This study does not support the hypothesis that sequential bilateral rTMS is more effective than unilateral high-frequency left-sided rTMS Studies of repetitive transcranial magnetic stimulation ( rTMS ) in depression have found antidepressant effects when high frequency stimulation ( HF-rTMS ; > 1 Hz ) is applied over the left prefrontal cortex ( LPF ) . A few studies have also reported success with low frequency stimulation ( LF-rTMS ) to the right prefrontal cortex ( RPF ) . Both HF-rTMS and LF-rTMS have been reported to work better in areas with cerebral hypometabolism or hypermetabolism , respectively . Thirty medication-resistant patients with major depression were r and omized into three groups . The first group received sham rTMS and the second group received active rTMS ( 20-Hz rTMS to the LPF and 1-Hz rTMS to the RPF ) . The third group , however , received active rTMS that was focused on different regions of the brain after examination with single photon emission computed tomography ( 20-Hz rTMS to an area of relatively low activity and 1-Hz rTMS to an area showing relatively high activation ) . Patients and raters were blind to the treatment condition . Comparison of the sham rTMS group with the overall group that received active rTMS revealed statistically significant changes on the Hamilton Rating Scale for Depression after 10 sessions . This study demonstrated that combined 20 + 1-Hz rTMS was effective , but no additional advantages were obtained by focusing rTMS on areas identified by single photon emission tomography as showing high versus low levels of functional activity BACKGROUND We tested whether transcranial magnetic stimulation ( TMS ) over the left dorsolateral prefrontal cortex ( DLPFC ) is effective and safe in the acute treatment of major depression . METHODS In a double-blind , multisite study , 301 medication-free patients with major depression who had not benefited from prior treatment were r and omized to active ( n = 155 ) or sham TMS ( n = 146 ) conditions . Sessions were conducted five times per week with TMS at 10 pulses/sec , 120 % of motor threshold , 3000 pulses/session , for 4 - 6 weeks . Primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Asberg Depression Rating Scale ( MADRS ) . Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale ( HAMD ) and response and remission rates with the MADRS and HAMD . RESULTS Active TMS was significantly superior to sham TMS on the MADRS at week 4 ( with a post hoc correction for ine quality in symptom severity between groups at baseline ) , as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6 . Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6 . Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales ( but not the HAMD17 scale ) . Active TMS was well tolerated with a low dropout rate for adverse events ( 4.5 % ) that were generally mild and limited to transient scalp discomfort or pain . CONCLUSIONS Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported . It offers clinicians a novel alternative for the treatment of this disorder OBJECTIVE Preliminary studies have indicated that daily left prefrontal repetitive transcranial magnetic stimulation might have antidepressant activity . The authors sought to confirm this finding by using a double-blind crossover design . METHOD Twelve depressed adults received in r and om order 2 weeks of active treatment ( repetitive transcranial magnetic stimulation , 20 Hz at 80 % motor threshold ) and 2 weeks of sham treatment . RESULTS Changes from the relevant phase baseline in scores on the 21-item Hamilton depression scale showed that repetitive transcranial magnetic stimulation significantly improved mood over sham treatment . During the active-treatment phase , Hamilton depression scale scores decreased 5 points , while during sham treatment the scores increased or worsened by 3 points . No adverse effects were noted . CONCLUSIONS These placebo-controlled results suggest that daily left prefrontal repetitive transcranial magnetic stimulation has antidepressant activity when administered at these parameters . Further controlled studies are indicated to explore optimal stimulation characteristics and location , potential clinical applications , and possible mechanisms of action In previous studies , fast repetitive transcranial magnetic stimulation ( rTMS ) with a frequency > 1 Hz demonstrated substantial antidepressant effects compared to sham rTMS . However , it is not clear whether fast rTMS is superior to slow rTMS ( frequency < or = 1 Hz ) which is safe at therapeutically promising higher intensities . The aim of this double-blind study was to compare the action of fast , slow and sham rTMS . Eighteen patients with pharmacotherapy-resistant major depression were r and omized to receive fast ( 10 Hz ) , slow ( 0.3 Hz ) or sham rTMS with 250 stimuli/day for 5 successive days . rTMS was applied at 90 % motor threshold intensity to the left dorsolateral prefrontal cortex . Scores on the Hamilton Depression Rating Scale ( HDRS ) , but not on the Montgomery-Asberg Depression Rating Scale ( MADRS ) , showed a statistically significant time x group interaction with a reduction of 19 % after slow rTMS . However , the effect was clinical ly marginal and not reflected by self-rating scores . Verbal memory and reaction performance were not impaired after rTMS , and there was even a statistically significant time x group interaction with improvement of verbal memory performance after fast rTMS . In conclusion , this study further supported the safety of rTMS but does not show any clinical ly meaningful antidepressant efficacy of rTMS at 250 daily stimuli over 5 days in pharmacotherapy-refractory major depression OBJECTIVE Selective serotonin reuptake inhibitors ( SSRIs ) are widely used to treat depression , but the rates , timing , and baseline predictors of remission in \" real world \" patients are not established . The authors ' primary objectives in this study were to evaluate the effectiveness of citalopram , an SSRI , using measurement-based care in actual practice , and to identify predictors of symptom remission in out patients with major depressive disorder . METHOD This clinical study included out patients with major depressive disorder who were treated in 23 psychiatric and 18 primary care \" real world \" setting s. The patients received flexible doses of citalop \n Output:\n " }, { "from": "agent", "value": "RESULTS rTMS was beneficial compared with sham for all outcomes .\nLimited evidence and variable treatment parameters prevented conclusions about which specific treatment options are more effective than others .\nFor MDD patients with 2 or more antidepressant treatment failures , rTMS is a reasonable , effective consideration" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: OBJECTIVE : To review the literature on strategies to optimize medication adherence in community-dwelling older adults and to make recommendations for clinical practice . METHODS : A systematic literature search was conducted using the MEDLINE , CINAHL , PsycINFO , International Pharmaceutical Abstract s , and EMBASE data bases for r and omized controlled trials examining strategies to optimize medication adherence in patients aged 65 or older prescribed long-term medication regimens . Additional studies were found by examining the reference lists of systematic review s and selected papers . 34 papers reporting on 33 studies met the eligibility criteria and were included in this review . RESULTS : Improvement in adherence was mixed across the studies examining educational interventions , with only 12 of the 28 studies showing improvement in adherence ; most were delivered by pharmacists . Effect sizes for the statistically significant educational interventions ranged from Cohen 's d = 0.14 to 4.93 . Four of the 5 interventions using memory aids and cues , some in conjunction with newer technologies , improved adherence . Effect sizes for the statistically significant interventions using memory aids and cues ranged from Cohen 's d = 0.26 to 2.72 . CONCLUSION : The evidence from this review does not clearly support one single intervention to optimize medication adherence in older patients . Future studies should explore suggestive strategies , such as tailored interventions involving ongoing contact , and should endeavor to correct method ologic weaknesses found in the literature OBJECTIVE To compare patients ' adherence to therapy , expectations , satisfaction with pharmacy services , and health-related quality of life ( HRQOL ) after the provision of pharmaceutical care with those of patients who received traditional pharmacy care . DESIGN R and omized controlled cluster design . SETTING Sixteen community pharmacies in Alberta , Canada . PATIENTS AND OTHER PARTICIPANTS Ambulatory elderly ( > or = 65 years of age ) patients covered under Alberta Health & Wellness 's senior drug benefit plan and who were concurrently using three or more medications according to pharmacy profiles . INTERVENTION Pharmacies were r and omly assigned to either treatment ( intervention ) or control ( traditional pharmacy care ) groups . Patients at treatment pharmacies were recruited into the study , and pharmacists provided comprehensive pharmaceutical care services . Pharmacists at control pharmacies continued to provide traditional pharmacy care . MAIN OUTCOME MEASURES Study participants ' opinions , adherence to therapy , and scores on the Medical Outcomes Study 36-Item Short Form Health Survey ( SF-36 ) . RESULTS Compared with those of patients receiving traditional care , treatment patients ' expectations that their pharmacist would perform activities congruent with pharmaceutical care changed over the study period . Treatment patients ' satisfaction with the constructs \" trust , \" \" evaluation and goal setting , \" and \" communicates with doctor \" were also positively affected . HRQOL and patient adherence were not significantly affected by pharmaceutical care interventions . CONCLUSION Successful implementation of a pharmaceutical care practice model has the potential to increase patients ' satisfaction with their pharmacists ' activities and may increase patients ' expectations that pharmacists will work on their behalf to assist them with their health care needs . If pharmaceutical care affects patients ' HRQOL , instruments more specific than the SF-36 may be needed to detect the differences RATIONALE , AIMS AND OBJECTIVES DEPICT ( Descriptive Elements of Pharmacist Intervention Characterization Tool ) was created in response to the frequently reported issue of poor intervention description across studies assessing the impact of clinical pharmacy activities . The aim of this study was to create an improved version of DEPICT ( i.e. DEPICT 2 ) to better characterize clinical pharmacy services in order to ensure consistent reporting , therefore enhancing reproducibility of interventions in practice . METHOD A qualitative approach through a thematic content analysis was performed to identify components of pharmacist interventions described in 269 r and omized controlled trials . A preliminary version of DEPICT 2 was applied independently by two authors to a r and om sample of 85 of the 269 RCTs and reliability determined by the prevalence-adjusted bias-adjusted kappa ( PABAK ) or the intraclass correlation coefficient ( ICC ) . The final version of DEPICT 2 was compared against DEPICT 1 . RESULTS The final version of DEPICT 2 comprised 146 items and 11 domains . The inter-rater agreement analysis showed that DEPICT presented good to optimal reproducibility , with a mean PABAK value of 0.87 ( 95 % CI 0.85 - 0.89 ) and a mean ICC value of 0.88 ( 95 % CI 0.62 - 1.14 ) . The mean difference between items checked in the two versions ( DEPICT 2 - DEPICT 1 ) was 10.58 ( 95 % CI 9.55 - 11.61 ) , meaning that approximately 11 more components were identified in the new version of DEPICT . CONCLUSIONS DEPICT 2 is a reliable tool to characterize components of clinical pharmacy services , which should be used to ensure consistent reporting of interventions to allow their reproducibility in practice The objective of this systematic review was to evaluate the impact of pharmacist delivered community-based services to optimise the use of medications for mental illness . Twenty-two controlled ( r and omised and non-r and omised ) studies of pharmacists ' interventions in community and residential aged care setting s identified in international scientific literature were included for review . Papers were assessed for study design , service recipient , country of origin , intervention type , number of participating pharmacists , method ological quality and outcome measurement . Three studies showed that pharmacists ' medication counselling and treatment monitoring can improve adherence to antidepressant medications among those commencing treatment when calculated using an intention-to-treat analysis . Four trials demonstrated that pharmacist conducted medication review s may reduce the number of potentially inappropriate medications prescribed to those at high risk of medication misadventure . The results of this review provide some evidence that pharmacists can contribute to optimising the use of medications for mental illness in the community setting . However , more well design ed studies are needed to assess the impact of pharmacists as members of community mental health teams and as providers of comprehensive medicines information to people with schizophrenia and bipolar OBJECTIVE : To compare medication adherence calculated from four different data sources including a pill count and self-report obtained during a home medication history , as well as calculations based on refill frequency derived from a provincial prescription cl aims data base ( manual and electronic ) . DESIGN : Baseline medication adherence was collected as part of a prospect i ve , r and omized , controlled study . Mean medication adherence results obtained from the four data sources were compared using repeated- measures ANOVA followed by a Tukey 's multiple range test . SETTING : A pharmacy consultation service located at an interdisciplinary wellness center for noninstitutionalized elderly . PATIENTS : 65 years or older , noninstitutionalized , taking one or more prescribed or nonprescribed medications . Clients would either present to the wellness center or be referred by the Provincial Home Care program . RESULTS : When calculated from self-report or manual or electronic prescription cl aims data , mean percent adherence by drug was high and not statistically different ( 95.8 % ± 17.1 % , 107.6 % ± 40.3 % , and 94.6 % ± 24.0 % , respectively ) , whereas the pill count adherence was significantly lower at 74.0 % ± 41.5 % ( p < 0.0001 ) . CONCLUSIONS : An unexpected finding was that the pill count technique used in this study of elderly clients using chronic , repeat medications appeared to underestimate medication adherence . Numerous other limitations of pill count , self-report , and a province-wide prescription cl aims data base in estimating medication adherence are presented . When using medication adherence as a process measure , the research er and practitioner should be aware of the limitations unique to the data source they choose , and interpret data cautiously The objectives of this study were to compare indices of 24-hour blood pressure ( BP ) following a physician-pharmacist collaborative intervention and to describe the associated changes in antihypertensive medications . This was a secondary analysis of a prospect i ve , cluster-r and omized clinical trial conducted in 6 family medicine clinics r and omized to co-managed ( n=3 clinics , 176 patients ) or control ( n=3 clinics , 198 patients ) groups . Mean ambulatory systolic BP ( SBP ) was significantly lower in the co-managed vs the control group : daytime BP 122.8 mm Hg vs 134.4 mm Hg ( P<.001 ) ; nighttime SBP 114.8 mm Hg vs 123.7 mm Hg ( P<.001 ) ; and 24-hour SBP 120.4 mm Hg vs 131.8 mm Hg ( P<.001 ) , respectively . Significantly more drug changes were made in the co-managed than in the control group ( 2.7 vs 1.1 changes per patient , P<.001 ) , and there was greater diuretic use in co-managed patients ( 79.6 % vs 62.6 % , P<.001 ) . Ambulatory BPs were significantly lower for the patients who had a diuretic added during the first month compared with those who never had a diuretic added ( P<.01 ) . Physician-pharmacist co-management significantly improved ambulatory BP compared with the control group . Antihypertensive drug therapy was intensified much more for patients in the co-managed group A consecutive sample of 64 healthy adults ( 33 female and 31 male ) were recruited at the University of Michigan Medical Center , Ann Arbor . Data were available for analysis on 57 subjects . The participants were asked to take a single daily dose of aspirin ranging from 0 to 640 mg . Adherence to the daily aspirin ingestion was measured by self-report and the Medication Event Monitoring System ( MEMS , Aprex Corp , Fremont , Calif ) ; adherence rate for the study population was 35 % . The adherence rates for all dosing errors between self-report and Medication Event Monitoring System were significantly different ( P = .002 ) . There was no significant gender difference in adherence rates . Adherence to regular aspirin ingestion was poor in healthy , paid subjects despite explicit , written and verbal instructions . Patient self-report alone is not a reliable measure of adherence BACKGROUND Nonadherence to cardiovascular medications is a significant public health problem . This r and omized study evaluated the effect on medication adherence of linking hospital and community pharmacists . METHODS Hospitalized patients with coronary artery disease discharged on aspirin , β-blocker , and statin who used a participating pharmacy were r and omized to usual care or intervention . The usual care group received discharge counseling and a letter to the community physician ; the intervention group received enhanced in-hospital counseling , attention to adherence barriers , communication of discharge medications to community pharmacists and physicians , and ongoing assessment of adherence by community pharmacists . The primary end point was self-reported use of aspirin , β-blocker , and statin at 6 months postdischarge ; the secondary end point was a ≥ 75 % proportion of days covered ( PDC ) for β-blocker and statin through 6 months postdischarge . RESULTS Of 143 enrolled patients , 108 ( 76 % ) completed 6-month follow-up , and 115 ( 80 % ) had 6-month refill records . There was no difference between intervention and control groups in self-reported adherence ( 91 % vs 94 % , respectively , P = .50 ) . Using the PDC to determine adherence to β-blockers and statins , there was better adherence in the intervention versus control arm , but the difference was not statistically significant ( 53 % vs 38 % , respectively , P = .11 ) . Adherence to β-blockers was statistically significantly better in intervention versus control ( 71 % vs 49 % , respectively , P = .03 ) . Of 85 patients who self-reported adherence and had refill records , only 42 ( 49 % ) were also adherent by PDC . CONCLUSIONS The trend toward better adherence by refill records with the intervention should encourage further investigation of engaging pharmacists to improve continuity of care This study was conducted to evaluate the effect of automated telephone patient monitoring and counseling on patient adherence to antihypertensive medications and on blood pressure control . A r and omized controlled trial was conducted in 29 greater Boston communities . The study subjects were 267 patients recruited from community sites who were > or= 60 years of age , on antihypertensive medication , with a systolic blood pressure ( SBP ) of > or= 160 mm Hg and /or a diastolic blood pressure ( DBP ) of > or= 90 mm Hg . The study compared subjects who received usual medical care with those who used a computer-controlled telephone system in addition to their usual medical care during a period of 6 months . Weekly , subjects in the telephone group reported self-measured blood pressures , knowledge and adherence to antihypertensive medication regimens , and medication side-effects . This information was sent to their physicians regularly . The main study outcome measures were change in antihypertensive medication adherence , SBP and DBP during 6 months , satisfaction of patient users , perceived utility for physicians , and cost-effectiveness . The mean age of the study population was 76.0 years ; 77 % were women \n Output:\n " }, { "from": "agent", "value": "Clinical pharmacy services that focused on specific medical conditions , such as hypertension or diabetes mellitus , revealed a positive impact of pharmacists ’ interventions on patient outcomes .\nFor other medical conditions , however , the results were inconclusive ( e.g. , dyslipidemia or thromboprophylaxis ) .\nInterventions that targeted medication adherence and assessed the impact of clinical pharmacy services in prescription appropriateness also produced inconclusive results because of the variability of methods used to assess both medication adherence and medication appropriateness .\nConclusions Systematic review s that assessed clinical pharmacy services targeting specific conditions were more conclusive given that the intervention was well defined , and the measured outcomes were unequivocal and tangible .\nConversely , the results were inconclusive for interventions with a broader target and with monitoring parameters that were unclearly established or inconsistently assessed across studies ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: OBJECTIVES : To determine the prevalence and characteristics of fetal alcohol spectrum disorders ( FASD ) among first grade students ( 6- to 7-year-olds ) in a representative Midwestern US community . METHODS : From a consented sample of 70.5 % of all first grade rs enrolled in public and private schools , an over sample of small children ( ≤25th percentile on height , weight , and head circumference ) and r and omly selected control c and i date s were examined for physical growth , development , dysmorphology , cognition , and behavior . The children ’s mothers were interviewed for maternal risk . RESULTS : Total dysmorphology scores differentiate significantly fetal alcohol syndrome ( FAS ) and partial FAS ( PFAS ) from one another and from unexposed controls . Alcohol-related neurodevelopmental disorder ( ARND ) is not as clearly differentiated from controls . Children who had FASD performed , on average , significantly worse on 7 cognitive and behavioral tests and measures . The most predictive maternal risk variables in this community are late recognition of pregnancy , quantity of alcoholic drinks consumed 3 months before pregnancy , and quantity of drinking reported for the index child ’s father . From the final multidisciplinary case findings , 3 techniques were used to estimate prevalence . FAS in this community likely ranges from 6 to 9 per 1000 children ( midpoint , 7.5 ) , PFAS from 11 to 17 per 1000 children ( midpoint , 14 ) , and the total rate of FASD is estimated at 24 to 48 per 1000 children , or 2.4 % to 4.8 % ( midpoint , 3.6 % ) . CONCLUSIONS : Children who have FASD are more prevalent among first grade rs in this Midwestern city than predicted by previous , popular estimates Objectives To determine the prevalence , patterns , and predictors of alcohol consumption prior to and during various intervals of pregnancy in the U.S. Methods Alcohol-related , pregnancy-related , and demographic data were derived from computer-assisted telephone interviews with 4,088 r and omly selected control mothers from the National Birth Defects Prevention Study who delivered live born infants without birth defects during 1997–2002 . Alcohol consumption rates and crude and adjusted odds ratios ( OR ) were calculated . Results 30.3 % of all women reported drinking alcohol at some time during pregnancy , of which 8.3 % reported binge drinking ( 4 + drinks on one occasion ) . Drinking rates declined considerably after the first month of pregnancy , during which 22.5 % of women reported drinking , although 2.7 % of women reported drinking during all trimesters of pregnancy and 7.9 % reported drinking during the 3rd trimester . Pre-pregnancy binge drinking was a strong predictor of both drinking during pregnancy ( adjusted OR = 8.52 , 95 % CI = 6.67–10.88 ) and binge drinking during pregnancy ( adjusted OR = 36.02 , 95 % CI = 24.63–52.69 ) . Other characteristics associated with both any drinking and binge drinking during pregnancy were non-Hispanic white race/ethnicity , cigarette smoking during pregnancy , and having an unintended pregnancy . Conclusions Our study revealed that drinking during pregnancy is fairly common , three times the levels reported in surveys that ask only about drinking during the month before the survey . Women who binge drink before pregnancy are at particular risk for drinking after becoming pregnant . Sexually active women of childbearing ages who drink alcohol should be advised to use reliable methods to prevent pregnancy , plan their pregnancies , and stop drinking before becoming pregnant BACKGROUND In Canada the incidence of Fetal Alcohol Spectrum Disorder ( FASD ) is estimated to be 1 in 100 live births . FASD is the leading cause of developmental and cognitive disabilities in Canada . Only one study has examined the cost of FASD in Canada . In that study we did not include prospect i ve data for infants under the age of one year , costs for adults beyond 21 years or costs for individuals living in institutions . OBJECTIVE To calculate a revised estimate of direct and indirect costs associated with FASD at the patient level . METHODS Cross-sectional study design was used . Two-hundred and fifty ( 250 ) participants completed the study tool . Participants included caregivers of children , youth and adults , with FASD , from day of birth to 53 years , living in urban and rural communities throughout Canada participated . Participants completed the Health Services Utilization Inventory ( HSUI ) . Key cost components were elicited : direct costs : medical , education , social services , out-of-pocket costs ; and indirect costs : productivity losses . Total average costs per individual with FASD were calculated by summing the costs for each in each cost component , and dividing by the sample size . Costs were extrapolated to one year . A stepwise multiple regression analysis was used to identify significant determinants of costs and to calculate the adjusted annual costs associated with FASD . RESULTS Total adjusted annual costs associated with FASD at the individual level was $ 21,642 ( 95 % CI , $ 19,842 ; $ 24,041 ) , compared to $ 14,342 ( 95 % CI , $ 12,986 ; $ 15,698 ) in the first study . Severity of the individual 's condition , age , and relationship of the individual to the caregiver ( biological , adoptive , foster ) were significant determinants of costs ( p < 0.001 ) . Cost of FASD annually to Canada of those from day of birth to 53 years old , was $ 5.3 billion ( 95 % CI , $ 4.12 billion ; $ 6.4 billion ) . CONCLUSIONS Study results demonstrated the cost burden of FASD in Canada was profound . Inclusion of infants aged 0 to 1 years , adults beyond the age of 21 years and costs associated with residing in institutions provided a more accurate estimate of the costs of FASD . Implication s for practice , policy , and research are discussed . Key words : Alcohol , pregnancy , cost , economic burden , fetal alcohol spectrum disorder OBJECTIVE We examined the use of alcohol during early pregnancy in urban Swedish women , the ability of Swedish antenatal care to identify alcohol-related risk pregnancies and the utility of some potential tools for improving its performance . METHOD Women attending regular antenatal care were r and omized to regular assessment only ( control , n = 156 ) or intensified screening ( intervention , n = 147 ) . In the intervention group , alcohol use was determined using the Timeline Followback ( TLFB ) interview , alcohol use habits with the Alcohol Use Disorder Inventory Test ( AUDIT ) , and biomarkers for alcohol use were analyzed . Data were typically obtained in pregnancy week 12 . RESULTS In the intervention group as a whole , average absolute alcohol consumption during the first 6 weeks of pregnancy was low but highly variable ( mean [ SD ] = 24.9 [ 50.5 ] g/week ; 4.8 [ 6.0 ] episodes for the entire 6 week period ) ; 22 women ( 15 % ) drank at levels exceeding 70 g/week during any 2 or more weeks and /or in a heavy episodic drinking pattern , 60 g/episode , on 2 or more episodes . The AUDIT had a moderate sensitivity ( 54 % ) to identify these subjects . Biomarkers identified subjects with somatic illness rather than high alcohol consumption . In the control group , only 4 ( 3 % ) were identified as using alcohol , indicating a probable underestimation of alcohol use by regular antenatal screening procedures ( p = .0001 ) . CONCLUSIONS An unexpected proportion of pregnant women in urban Sweden consume alcohol at levels likely to produce adverse effects . Regular antenatal care did not identify most of these risk pregnancies . The TLFB identified pregnant women with risk use of alcohol during pregnancy who were only partly identified by analyzing prepregnancy alcohol use patterns with the AUDIT . Elevated laboratory markers likely indicated somatic illness rather than harmful drinking BACKGROUND The prevalence and characteristics of fetal alcohol spectrum disorders ( FASD ) were determined in this fourth study of first- grade children in a South African community . METHODS Active case ascertainment methods were employed among 747 first- grade pupils . The detailed characteristics of children within the continuum of FASD are contrasted with r and omly selected , normal controls on ( i ) physical growth and dysmorphology ; ( ii ) cognitive/behavioral characteristics ; and ( iii ) maternal risk factors . RESULTS The rates of specific diagnoses within the FASD spectrum continue to be among the highest reported in any community in the world . The prevalence ( per 1,000 ) is as follows : fetal alcohol syndrome (FAS)-59.3 to 91.0 ; partial fetal alcohol syndrome (PFAS)-45.3 to 69.6 ; and alcohol-related neurodevelopmental disorder (ARND)-30.5 to 46.8 . The overall rate of FASD is therefore 135.1 to 207.5 per 1,000 ( or 13.6 to 20.9 % ) . Clinical profiles of the physical and cognitive/behavioral traits of children with a specific FASD diagnosis and controls are provided for underst and ing the full spectrum of FASD in a community . The spectral effect is evident in the characteristics of the diagnostic groups and summarized by the total ( mean ) dysmorphology scores of the children : FAS = 18.9 ; PFAS = 14.3 ; ARND = 12.2 ; and normal controls , alcohol exposed = 8.2 and unexposed = 7.1 . Documented drinking during pregnancy is significantly correlated with verbal ( r = -0.253 ) and nonverbal ability ( r = -0.265 ) , negative behaviors ( r = 0.203 ) , and total dysmorphology score ( r = 0.431 ) . Other measures of drinking during pregnancy are significantly associated with FASD , including binge drinking as low as 3 drinks per episode on 2 days of the week . CONCLUSIONS High rates of specific diagnoses within FASD were well documented in this new cohort of children . FASD persists in this community . The data reflect an increased ability to provide accurate and discriminating diagnoses throughout the continuum of FASD OBJECTIVE To study the activities of serum gamma-glutamyltransferase ( GGT ) , aspartate and alanine aminotransferases ( AST , ALT ) , and their ratio ( AST/ALT ) , mean erythrocyte cell volume ( MCV ) and urinary dolichol output in alcohol-abusing pregnant women , and compare the results to those of abstinent pregnant women . DESIGN Prospect i ve descriptive study . SETTING Special outpatient clinic for pregnant problem-drinkers in the department of Obstetrics and Gynaecology , Helsinki University Central Hospital , Finl and . SUBJECTS 25 pregnant women referred to the special clinic at between 12 and 24 weeks gestation , they consumed at least 150 g of ethanol weekly , and a control group of 20 abstinent pregnant women matched for age , parity and smoking habits . INTERVENTIONS The women were encouraged to visit the clinic at 2 - 4 week intervals . At each visit blood and urine sample s were obtained , and the women were interviewed on their alcohol consumption during the previous weeks and encouraged to abstain in the future . MEAN OUTCOME MEASURES Neonatal condition , fetal alcohol effects ( FAE ) in the newborn . Serum activities of GGT , AST and ALT , the AST/ALT ratio , the MCV , and the urinary concentration of dolichol in alcohol-abusing women with either healthy or FAE infants , compared with those of abstinent women with healthy infants . RESULTS Of the 25 alcohol-abusing women 13 gave birth to infants with FAE and 12 to healthy infants . All the women in the control group gave birth to healthy infants . GGT , AST and ALT activities were increased in all alcohol-abusing women , regardless whether the infant had FAE or not . GGT was the best of these markers , GGT activities above the 95th normal centile were found in 33 % of the sample s from all alcohol-abusing women . The AST/ALT ratio , MCV and urinary dolichol concentration were poor indicators of abusive drinking . CONCLUSIONS Maternal alcohol abuse is difficult to assess by laboratory tests . Of the commonly used and easily available tests , GGT proved to be the best in our study In order to investigate prospect ively in pregnant women a correlation between serum levels of a biological marker of alcohol and the clinical status of the newborn , we measured the gamma-glutamyltransferase ( GGT ) in 630 women between 14 and 20 weeks of pregnancy . In 7 % of the cases , an elevated value was observed while history confirmed alcohol consumption in only 1 % . Preliminary statistical analysis established upon the blind examination of 308 newborns show a correlation between maternal GGT levels and birthweight as well as the pre- and perinatal complications . However , the sensitivity of this test is weak BACKGROUND The prevalence and characteristics of fetal alcohol syndrome ( FAS ) and partial FAS ( PFAS ) in the United States ( US ) are not well known . METHODS This active case ascertainment study in a Rocky Mountain Region City assessed the prevalence and traits of children with FAS and PFAS and linked them to maternal risk factors . Diagnoses made by expert clinical dysmorphologists in multidisciplinary case conferences utilized all components \n Output:\n " }, { "from": "agent", "value": "Although all of the studies were rated of good method ological quality , none of the biomarkers had both high sensitivity and specificity when compared to self-report .\nThere was some evidence that a combination of biomarkers , or combining biomarkers with self-report , increases accuracy .\nIn summary , the blood biomarkers examined were of limited use in screening for low and moderate alcohol consumption in pregnancy when compared to self-report .\nHowever , certain biomarkers , such and CDT and PEth may complement self-report and help improve the accuracy of diagnosis" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: INTRODUCTION The efficacy of contingency-management ( CM ) and motivational enhancement therapy ( MET ) for college student smoking cessation was examined . METHODS Nontreatment-seeking daily smokers ( N = 110 ) were r and omly assigned to 3 weeks of CM versus noncontingent reinforcement ( NR ) and to three individual sessions of MET versus a relaxation control in a 2 x 2 experimental design . Expired carbon monoxide ( CO ) sample s were collected twice daily for 3 weeks . Participants earned 5 US dollars for providing each sample ; additionally , those r and omized to CM earned escalating monetary rewards based on CO reductions ( Week 1 ) and smoking abstinence ( Weeks 2 - 3 ) . RESULTS Compared with NR , CM result ed in significantly lower CO levels and greater total and consecutive abstinence during the intervention . Those in the CM and MET groups reported greater interest in quitting smoking posttreatment , but rates of confirmed abstinence at follow-up were very low ( 4 % at 6-month follow-up ) and did not differ by group . DISCUSSION Findings support the short-term efficacy of CM for reducing smoking among college students . Future research should explore enhancements to CM in this population , including a longer intervention period and the recruitment of smokers who are motivated to quit Chronic Obstructive Pulmonary Disease ( COPD ) usually results from tobacco smoking . Smoking cessation slows COPD 's progression , but few have studied anti-smoking treatments in COPD . In 3-month trials we paid lottery tickets during daily home visits to still-smoking COPD patients for reductions in breath carbon monoxide ( CO ) , a measure of smoke intake . In our first protocol experimental patients received 0 - 3 tickets per day , depending upon the extent of CO reduction below pre-treatment baselines ; yoked controls received the same number of tickets , but not contingent on CO . The protocol produced no change . In a second study patients were assigned a post-baseline quit- date , received nicotine gum , and were paid up to 5 tickets per night , but only for CO less than 10 parts per million ( ppm ) . CO fell sharply as the intervention began , but gradually rose again . A third protocol added special reinforcement schedules for those who did not quit or relapsed ( up to 20 tickets per night for CO less than 10 ppm ) . Daily CO concentrations fell from 27.1 parts per million ( baseline mean ) to 12.7 ( intervention mean ) , but rapid increases followed the intervention . Few patients stopped smoking , but CO and cigarettes used per day significantly fell during Studies 2 and 3 . Post-hoc analysis suggested only a small effect from gum Rationale Sustaining smoking abstinence during the initial weeks of a cessation effort is highly correlated with long-term smoking abstinence . However , experimental research is needed to establish a direct causal relationship between achieving early abstinence and lowered relapse risk . Objective In the present study , we tested whether a period of sustained abstinence directly decreases the relative reinforcing effects of cigarette smoking . Methods Participants were 63 adult smokers who were r and omized into one of three conditions : 14-day ( 14C ) , 7-day ( 7C ) , and 1-day ( 1C ) contingent payment for smoking abstinence . Smoking status was assessed three times per day for 14 consecutive days using breath carbon monoxide monitoring and an abstinence criterion of ≤4 ppm . In the 14C condition , monetary payment was contingent on abstinence for all 14 days ; in the 7C condition , payment was noncontingent for days 1–7 and contingent for days 8–14 ; in the 1C condition , payment was noncontingent for days 1–13 and contingent for day 14 . On day 14 , all participants completed a 3-h preference session under controlled laboratory conditions wherein they could make a maximum of 20 exclusive choices between options to smoke ( two puffs/choice ) or earn money ( $ 0.25/choice ) . Preference was deemed an index of the relative reinforcing effects of smoking and money . Results A significantly lower proportion of participants in the 14C condition ever chose the smoking option ( 19 % ) compared to those in the 7C ( 57 % ) or 1C ( 62 % ) conditions . Conclusions These results provide experimental evidence that sustained abstinence can decrease the relative reinforcing effects of smoking , an effect that may be related to the commonly observed decrease in relapse risk among those who are able to sustain smoking abstinence during the initial weeks of a cessation effort Medication noncompliance with smoking cessation pharmacotherapies is a significant problem in both research and clinical setting s. This r and omized , controlled , single-blind study compared three single-session psychological interventions to increase use of nicotine gum during a 15-day treatment period . A total of 97 adult smokers were r and omized to receive st and ard treatment ( ST , n = 31 ) , brief feedback ( BF , n = 32 ) plus ST , or contingency management ( CM ; i.e. , payment for chewing at least 12 pieces/day on 10 of 15 intervention days , n = 34 ) plus ST and BF . Only the CM condition led to significantly greater average daily gum use ( pieces/day : ST , 6.17 ; BF , 7.81 ; CM , 10.17 [ p values < .05 ] ) and higher rates of compliance ( ST , 13.6 % ; BF , 25.2 % ; CM , 65.6 % [ p values < .001 ] ) . No differences were observed in smoking abstinence , nicotine withdrawal , or urinary cotinine as a function of treatment . Implication s of the present findings are discussed , including application to clinical trials and extension to real-world use of nicotine gum Background . There have been few reports of the process of implementing ongoing worksite health promotion programs . This article describes the implementation of a year-long smoking cessation program in nine worksites employing a total of approximately 700 smokers . Methods . Issues discussed include : forming a partnership with organizations , design of the multicomponent incentive intervention , program promotion , maintaining participation , and the need to modify program components over time . Results . The program produced high participation rates ( 29 % of smokers joined the program ) and moderate cessation rates among participants ( during the last half of the program , monthly cessation rates averaged 20 % ) . There was marked variability across worksites on both participation and cessation , and qualitative features of organizations associated with outcome are discussed . Discussion . The importance of working with employee steering committees to tailor health promotion programs to fit the organization is discussed . The article concludes with recommendations for implementation of similar programs Purpose . To determine the effectiveness of a multicomponent smoking cessation program supplemented by incentives and team competition . Design . A quasi-experimental design was employed to compare the effectiveness of three different smoking cessation programs , each assigned to separate worksites . Setting . The study was conducted from 1990 to 1991 at three aerospace industry worksites in California . Subjects . All employees who were current , regular tobacco users were eligible to participate in the program offered at their site . Intervention . The multicomponent program included a self-help package , telephone counseling , and other elements . The incentive-competition program included the multicomponent program plus cash incentives and team competition for the first 5 months of the program . The traditional program offered a st and ard smoking cessation program . Measures . Self-reported question naires and carbon monoxide tests of tobacco use or abstinence were used over a 12-month period . Results . The incentive-competition program had an abstinence rate of 41 % at 6 months ( n = 68 ) , which was significantly better than the multicomponent program ( 23 % , n = 81 ) or the traditional program ( 8 % , n = 36 ) . At 12 months , the quit rates for the incentive and multicomponent programs were statistically indistinguishable ( 37 % vs. 30 % ) , but remained higher than the traditional program ( 11 % ) . Chi-square tests , t-tests , and logistic regression were used to compare smoking abstinence across the three programs . Conclusions . Offering a multicomponent program with telephone counseling may be just as effective for long-term smoking cessation as such a program plus incentives and competition , and more effective than a traditional program Biochemical validation of smoking status has long been considered essential , but recent reports have question ed its utility in certain kinds of field trials . We describe efforts to biochemically vali date self-reports of smoking cessation from participants in four large-scale r and omized trials in outpatient clinics , hospitals , worksites , and dental clinics . These studies included over 5,000 adults smokers who participated in the population -based low-intensity intervention evaluations . At a 1-year follow-up , 798 subjects reported no tobacco use . We attempted to verify these reports using saliva continine/carbon monoxide validation procedures . Overall , there was a moderately high nonparticipation rate ( 27 % ) , a low disconfirmation rate ( 4 % ) , and a high self-reported relapse rate ( 12 % ) in the interval between survey and biochemical validation . There were no differences between intervention and control conditions on any of the above variables . Longer duration s of self-reported abstinence were strongly related to increased probability of biochemical confirmation . Differences in results across projects were related to how biochemical validation was conducted . These results , as well as statistical power considerations , raise questions about whether biochemical validation procedures are practical , informative , or cost-effective in such population -based , low-intensity intervention research This study determined the effects on smoking behavior of providing contingent reinforcement for nonsmoking versus reduced smoking afternoon breath carbon monoxide ( CO ) target levels . Twenty-eight hired chronic smoker volunteers were r and omly assigned to one of three experimental conditions during a 10-day intervention : ( a ) 8 ppm target CO , $ 5 per day incentive ( n = 11 ) ; ( b ) 16 ppm target CO , $ 4 per day incentive ( n = 8) ; or ( c ) 8 ppm target CO , no incentive ( n = 9 ) . Both payment groups showed significantly lower CO levels and greater amounts of daytime smoking reduction than the no-pay group . A specific effect of CO target was also seen ; 45 % of subjects in the 8 ppm group compared with 0 % of subjects in the 16 ppm target and no-pay groups produced average afternoon CO levels of 8.5 ppm or lower during the intervention . Average levels of CO and smoking reduction did not differ for the two paid groups , however , because some subjects in the 8 ppm group failed to reduce CO sufficiently to contact the reinforcer . Contingent reinforcement based on expired air CO levels can exercise powerful and precise ( target-specific ) control over smoking behavior , but there may be individual differences in ability to meet reinforcement contingencies if difficult targets are introduced abruptly The relationship between reinforcer amount and daytime smoking reduction in smokers offered money for reduced afternoon breath carbon monoxide ( CO ) levels was examined . Twenty-three hired regular smokers with average baseline CO levels of about 30 ppm were exposed in r and om order to five sliding scale payment schedules that changed daily or weekly . Money was available for afternoon CO readings between 0 and 21 ppm with pay amount inversely related to the absolute CO reading obtained . Maximum pay amount for readings below 7 ppm varied among $ 0 , $ 1.50 , $ 3 , $ 6 , and $ 12 per day . Contingent reinforcement promoted CO and daytime cigarette reduction within individuals with the amount of behavior change related to the amount of payment available . Average CO levels decreased from 30 to 15 ppm as a function of pay amount whereas self-reported daytime cigarettes decreased from 12 to 5 per day . Average minutes of cigarette abstinence prior to the afternoon study contact increased from 62 to 319 minutes as a function of pay amount , whereas the percentage of available money earned increased from 22 % to 48 % . Nontargeted evening cigarette use also decreased during periods of daytime smoking reduction . The orderly effects of this contingent reinforcement intervention on daytime smoking of regular smoker volunteers suggest that this is a sensitive model for continued evaluation of factors that influence smoking reduction and cessation BACKGROUND Smoking is the leading preventable cause of premature death in the United States . Previous studies of financial incentives for smoking cessation in work setting s have not shown that such incentives have significant effects on cessation rates , but these studies have had limited power , and the incentives used may have been insufficient . METHODS We r and omly assigned 878 employees of a multinational company based in the United States to receive information about smoking-cessation programs ( 442 employees ) or to receive information about programs plus financial incentives ( 436 employees ) . The financial incentives were $ 100 for completion of a smoking-cessation program , $ 250 for cessation of smoking within 6 months after study enrollment , as confirmed by a biochemical test , and $ 400 for abstinence for an additional 6 months after the initial cessation , as confirmed by a biochemical test . Individual participants were stratified according to work site , heavy or nonheavy smoking , and income . The primary end point was smoking cessation 9 or 12 months after enrollment , depending on whether initial cessation was reported at 3 or 6 months . Secondary end points were smoking cessation within the first 6 months after enrollment and rates of participation in and completion of smoking-cess \n Output:\n " }, { "from": "agent", "value": "In the remaining trials , there was no clear evidence that participants who committed their own money to the programme did better than those who did not , or that contingent rewards enhanced success rates over fixed payment schedules .\nThere is some evidence that recruitment rates can be improved by rewarding participation , which may be expected to deliver higher absolute numbers of successful quitters .\nWith the exception of one recent trial , incentives and competitions have not been shown to enhance long-term cessation rates .\nEarly success tended to dissipate when the rewards were no longer offered .\nRewarding participation and compliance in contests and cessation programmes may have potential to deliver higher absolute numbers of quitters ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: The importance of adherence to antihypertensive treatments for the prevention of cardiovascular disease has not been well eluci date d. This study evaluated the effect of antihypertensive medication adherence on specific cardiovascular disease mortality ( ischemic heart disease [ IHD ] , cerebral hemorrhage , and cerebral infa rct ion ) . Our study used data from a 3 % sample cohort that was r and omly extracted from enrollees of Korean National Health Insurance . Study subjects were aged ≥20 years , were diagnosed with hypertension , and started newly prescribed antihypertensive medication in 2003 to 2004 . Adherence to antihypertensive medication was estimated as the cumulative medication adherence . Subjects were divided into good ( cumulative medication adherence , ≥80 % ) , intermediate ( cumulative medication adherence , 50%–80 % ) , and poor ( cumulative medication adherence , < 50 % ) adherence groups . We used time-dependent Cox proportional hazards models to evaluate the association between medication adherence and health outcomes . Among 33 728 eligible subjects , 670 ( 1.99 % ) died of coronary heart disease or stroke during follow-up . Patients with poor medication adherence had worse mortality from IHD ( hazard ratio , 1.64 ; 95 % confidence interval , 1.16–2.31 ; P for trend=0.005 ) , cerebral hemorrhage ( hazard ratio , 2.19 ; 95 % confidence interval , 1.28–3.77 ; P for trend=0.004 ) , and cerebral infa rct ion ( hazard ratio , 1.92 ; 95 % confidence interval , 1.25–2.96 ; P for trend=0.003 ) than those with good adherence . The estimated hazard ratios of hospitalization for cardiovascular disease were consistent with the mortality end point . Poor medication adherence was associated with higher mortality and a greater risk of hospitalization for specific cardiovascular diseases , emphasizing the importance of a monitoring system and strategies to improve medication adherence in clinical practice ABSTRACT Introduction : This study was aim ed at evaluating whether once-daily regimens ( od-r ) show benefits in adherence when compared to twice-daily ( td-r ) . Methods : Prospect i ve , multicenter , 6-month follow-up study with two visits . The main objective was to compare adherence assessed by the electronic prescription refill rate ( EPRR ) and by the 10-item Test of Adherence to Inhalers ( TAI ) in patients with od-r and td-r . Suboptimal adherence was defined as TAI < 50 or EPRR ≤ 80 % . The effect of suboptimal adherence on meaningful clinical outcomes and the concordance between EPRR and TAI were also examined . Results : One hundred and ninety-seven patients ( 47.3 ± 15.9 years , 65 % women ) were included and 180 completed the study . TAI score was < 50 in 29.8 % od-r patients and 46.9 % in td-r ( p = 0.01 ) and EPRR was ≤80 % in 22.6 % and 37.5 % respectively ( p = 0.02 ) . The correlation between the two methods was moderate ( rho = 0.548 ; p < 0.001 ) . There were no significant differences in FEV1 ( % ) , symptoms or exacerbations between patients with optimal and suboptimal adherence . During follow-up , five patients ( 6 % ) with o-dr and 17 patients ( 17.7 % ) with t-dr suffered an exacerbation ( p = 0.013 ) . At visit two , 13.1 % of the patients with o-dr and 31.3 % with t-dr had uncontrolled asthma ( p = 0.003 ) , although more patients with o-dr were receiving inhaled corticosteroids in the high-dose stratum ( 25.8 % vs. 11.5 % ; p = 0.001 ) . Conclusion : Mean adherence rates were greater with od-r than with td-r , but we did not observe an effect on clinical outcomes OBJECTIVES The primary aims of the study were to : ( a ) describe the trajectories of adherence to daily inhaled corticosteroid ( ICS ) medication for a year in economically disadvantaged , African-American youth with asthma based on growth curve modeling ; and ( b ) test the relationship of treatment adherence to symptom control , quick-relief medication , and healthcare utilization . METHODS This prospect i ve study measured adherence to daily ICS treatment using electronic monitoring in 92 children and adolescents with moderate to severe asthma for 9 - 12 months and assessed clinical outcomes , including asthma-related symptoms , quick-relief medication , and healthcare utilization . RESULTS Youth showed a decrement in treatment adherence to less than half of prescribed corticosteroid treatment over the course of the study , which related to increased healthcare utilization ( p < .04 ) , but not to asthma symptoms or albuterol use . CONCLUSION Economically disadvantaged youth with asthma demonstrate high rates of chronic nonadherence that warrant identification and intervention to reduce asthma-related healthcare utilization The assessment of compliance is critical in the evaluation of the effectiveness of a new therapeutic agent . Fifteen patients with transfusion-dependent beta-thalassemia , many of whom had previously demonstrated erratic compliance with deferoxamine , were enrolled in a clinical trial of a new oral iron chelator , 1,2-dimethyl-3-hydroxypyrid-4-one ( L1 ) . Their compliance with this medication was estimated by several existing methods and the novel Medication Event Monitoring System ( MEMS ) . Overall compliance as assessed by the MEMS was 78.5 + /- 13.0 % of prescribed doses taken , significantly lower than the corresponding rates calculated by pill counts and diaries ( 91.5 + /- 9.2 % and 94.1 + /- 4.3 % , respectively ) . However , several serious problems were encountered with the MEMS , mostly in the form of incorrect use of the device by the patients . Disclosure of the nature of the MEMS and the compliance monitoring process did not alter the rate of adherence with L1 therapy . Compliance as determined by pill counts did not differ between the 1st and 2nd 6-month periods . Although not reaching statistical significance , a trend towards better L1 compliance occurred in those patients in whom serum ferritin levels decreased . Patients who filled at least 50 % of their diaries had significantly better compliance by pill counts than those who completed less than 50 % of their diaries ( 95.9 + /- 4.1 % and 86.5 + /- 11.1 % , respectively ) . Steady-state L1 trough concentrations and 24-hour urinary iron excretion did not correlate with L1 compliance . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Patients who adhere to medications experience better outcomes than their nonadherent counterparts . However , these observations may be confounded by patient behaviors . The level of adherence necessary for patients to derive benefit and whether adherence to all agents is important for diseases that require multiple drugs remain unclear . This study quantifies the relationship between medication adherence and post-myocardial infa rct ion ( MI ) adverse coronary events . METHODS This is a secondary analysis of the r and omized MI FREEE trial . Patients who received full prescription coverage were classified as adherent ( proportion of days covered ≥80 % ) or not based upon achieved adherence in the 6 months after r and omization . First major vascular event or revascularization rates were compared using multivariable Cox models adjusting for comorbidity and health-seeking behavior . RESULTS Compared with patients r and omized to usual care , full coverage patients adherent to statin , β-blocker , or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker were significantly less likely to experience the study 's primary outcome ( hazard ratio [ HR ] range 0.64 - 0.81 ) . In contrast , nonadherent patients derived no benefit ( HR range 0.98 - 1.04 , P ≤ .01 for the difference in HRs between adherent and nonadherent patients ) . Partially adherent patients had no reduction in clinical outcomes for any of the drugs evaluated , although their achieved adherence was higher than that among controls . CONCLUSION Achieving high levels of adherence to each and all guideline -recommended post-MI secondary prevention medication is associated with improved event-free survival . Lower levels of adherence appear less protective BACKGROUND Unmeasured confounders and selection bias can significantly influence the results of retrospective observational analyses of asthma therapy . OBJECTIVE To evaluate the efficacy of oral montelukast and inhaled fluticasone propionate in a r and omized , prospect i ve 12-month \" real-world \" observational analysis of children with mild persistent asthma . METHODS Children ( n = 104 ) between 6 and 15 years of age with mild asthma as determined by forced expiratory volume in 1 second , symptoms , and evaluation by an experienced pediatric allergist or pulmonologist , who were not currently receiving controller therapy , were r and omly assigned to fluticasone or montelukast on an alternating basis . Subjects were asked to complete a question naire at 6 and 12 months ; otherwise , medical care was identical to that of similar managed care patients . Outcome parameters were evaluated after 12 months by cl aims data base analysis . An acute asthma attack requiring emergent care was the primary outcome parameter . Measures of adherence , symptoms , and asthma control , as measured by the pediatric Asthma Therapy Assessment Question naire , were secondary outcome parameters . RESULTS Demographics , spirometry , symptoms at enrollment , emergent care visits , asthma hospitalizations , routine office visits , and symptoms at study completion were not significantly different between study groups . Adherence , as evaluated by the number of controller fills , was significantly ( P = 0.0003 ) better for montelukast ( 7.65 + /- 3.01 ) than fluticasone ( 5.46 + /- 3.01 ) . Similar numbers of subjects in each study group required beta-agonists and oral prednisone . CONCLUSIONS These results suggest that oral montelukast and inhaled fluticasone have similar real-world efficacies in the treatment of children with mild asthma , possibly as a result of the significantly better adherence with oral montelukast therapy compared with inhaled fluticasone BACKGROUND Being able to identify patients at risk of exacerbations is useful as it enables re sources to be targeted at these patients . AIMS To test the theoretically-derived prediction that the frequency of non-asthma related visits to the general practitioner ( GP ) predicts exacerbations . METHODS Clinical and demographic data and both self-report and prescription-based adherence data were obtained from 166 patients diagnosed with asthma attending a GP clinic , all of whom were prescribed inhaled corticosteroids ( ICS ) . Asthma exacerbations ( treated by the GP or in hospital ) and non-asthma visits and symptoms were assessed from notes for the subsequent 5 years . RESULTS Exacerbations correlated with non-asthma visits ( 0.35 ) , severity as measured by BTS step ( 0.28 ) , and with prescription-based adherence ( 0.28 ) . Asthma severity correlated with non-asthma visits ( 0.35 ) . Receiver operating curves showed that ≥2 non-asthma visits per year provided 79 % sensitivity and 58 % specificity for detecting ≥3 exacerbations over 5 years . Poor adherence predicted outcomes only for patients with high levels of non-asthma visits ( ≥3 ) and only for those reporting regular-but-less ICS use but not symptom-directed ICS use . CONCLUSIONS Non-asthma visits are a good predictor of asthma exacerbations , particular in non-adherent patients . These results are consistent with a mechanism where exacerbations result from a combination of r and om oscillating specific and non-specific inflammatory processes . It is important to consider the total patient rather than just the lung when managing patients with asthma BACKGROUND Information comparing subjective and objective measurements of adherence to study medications and the effects of adherence on treatment-related differences in asthma clinical trials are limited . OBJECTIVE We sought to compare subjective and objective measurements of children 's adherence to inhaled corticosteroids or placebo and to determine whether adherence to study medications modified treatment-related differences in outcomes . METHODS In an ancillary study conducted in 3 of 8 Childhood Asthma Management Program Clinical Centers , adherence was assessed by using self-reported and objective data in 5- to 12-year-old children with mild or moderate asthma who were r and omly assigned to 200 μg of inhaled budesonide twice per day ( n = 84 ) or placebo ( n = 56 ) for 4 years . The κ statistic was used to evaluate agreement between self-reported adherence ( daily diary cards ) and objective ly measured adherence ( number of doses left in study inhalers ) . Multivariable analyses were used to determine whether adherence to study treatment modified treatment-related differences in out \n Output:\n " }, { "from": "agent", "value": "The highest reduction in the odds of exacerbation was associated with patients achieving 80 % or more adherence , and the odds also reduced among those with 50 % or more adherence , whereas a substantial increase in exacerbation was associated with discontinuation of therapy" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: BACKGROUND Reduced rank regression ( RRR ) has been used to derive dietary pattern scores that predict linear combinations of disease biomarkers . The generalizability of these patterns to independent population s remains unknown . OBJECTIVE The goal was to examine the generalizability of dietary patterns from the following prior studies using RRR to predict type 2 diabetes mellitus ( T2DM ) : the Nurses ' Health Study ( NHS ) , European Prospect i ve Investigation into Cancer and Nutrition Germany ( EPIC ) , and Whitehall II Study ( WS ) . DESIGN The relative weights of food groups of each dietary pattern were used to generate each dietary pattern score in the Framingham Offspring Study ( n = 2879 ) . Each of the external scores ( confirmatory scores ) was examined to determine whether it could predict incident T2DM during 7 y of follow-up as well as scores developed internally in the Framingham Offspring Study using a Cox-proportional hazard model adjusted for T2DM risk factors . RESULTS Intakes of meat products , refined grains , and soft drinks ( caloric and noncaloric ) were found to be common predictive components of all confirmatory scores , but fried foods , eggs , and alcoholic beverages were predictive in some , but not in all , confirmatory scores . On the basis of a continuous increase in the score by 1 SD , the NHS-based confirmatory score predicted T2DM risk ( hazard ratio : 1.44 ; 95 % CI : 1.25 , 1.66 ) . However , T2DM risk was only weakly predicted by the EPIC-based score ( hazard ratio : 1.14 ; 95 % CI : 0.99 , 1.32 ) and the WS-based score ( hazard ratio : 1.16 ; 95 % CI : 1.00 , 1.35 ) . CONCLUSIONS The study suggested that dietary patterns that predict T2DM risk in different population s may not be generalizable to different population s. Additional dietary pattern studies should be conducted with regard to generalizability Carbohydrate-restricted diets ( CRDs ) have been shown to reduce body weight , whereas whole egg intake has been associated with increased satiety . The purpose of this study was to evaluate the effects of additional dietary cholesterol and protein provided by whole eggs while following a CRD on insulin resistance and appetite hormones . Using a r and omized blind parallel design , subjects were allocated to an egg ( 640 mg/d additional dietary cholesterol ) or placebo ( 0 mg/d additional dietary cholesterol ) group for 12 weeks while following a CRD . There were significant reductions in fasting insulin ( P < .025 ) and fasting leptin concentrations ( P < .01 ) for both groups , which were correlated with the reductions in body weight and body fat ( P < .05 and P < .01 , respectively ) . Both groups reduced insulin resistance as measured by the homeostatic model assessment of insulin resistance ( P < .025 ) . There was a significant decrease in serum glucose levels observed after the intervention . We did not observe the expected increases in plasma ghrelin levels associated with weight loss , suggesting a mechanism by which subjects do not increase appetite with CRD . To confirm these results , the subjective measures of satiety using visual analog scale showed that both groups felt more \" full \" ( P < .05 ) , \" satisfied \" ( P < .001 ) , and \" wanted to eat less \" ( P < .001 ) after the intervention . These results indicate that inclusion of eggs in the diet ( additional dietary cholesterol ) did not modify the multiple beneficial effects of CRD on insulin resistance and appetite hormones Background Our aim was to compare the effects of a Paleolithic ( ' Old Stone Age ' ) diet and a diabetes diet as generally recommended on risk factors for cardiovascular disease in patients with type 2 diabetes not treated with insulin . Methods In a r and omized cross-over study , 13 patients with type 2 diabetes , 3 women and 10 men , were instructed to eat a Paleolithic diet based on lean meat , fish , fruits , vegetables , root vegetables , eggs and nuts ; and a Diabetes diet design ed in accordance with dietary guidelines during two consecutive 3-month periods . Outcome variables included changes in weight , waist circumference , serum lipids , C-reactive protein , blood pressure , glycated haemoglobin ( HbA1c ) , and areas under the curve for plasma glucose and plasma insulin in the 75 g oral glucose tolerance test . Dietary intake was evaluated by use of 4-day weighed food records . Results Study participants had on average a diabetes duration of 9 years , a mean HbA1c of 6,6 % units by Mono-S st and ard and were usually treated with metformin alone ( 3 subjects ) or metformin in combination with a sulfonylurea ( 3 subjects ) or a thiazolidinedione ( 3 subjects ) . Mean average dose of metformin was 1031 mg per day . Compared to the diabetes diet , the Paleolithic diet result ed in lower mean values of HbA1c ( -0.4 % units , p = 0.01 ) , triacylglycerol ( -0.4 mmol/L , p = 0.003 ) , diastolic blood pressure ( -4 mmHg , p = 0.03 ) , weight ( -3 kg , p = 0.01 ) , BMI ( -1 kg/m2 , p = 0.04 ) and waist circumference ( -4 cm , p = 0.02 ) , and higher mean values of high density lipoprotein cholesterol ( + 0.08 mmol/L , p = 0.03 ) . The Paleolithic diet was mainly lower in cereals and dairy products , and higher in fruits , vegetables , meat and eggs , as compared with the Diabetes diet . Further , the Paleolithic diet was lower in total energy , energy density , carbohydrate , dietary glycemic load , saturated fatty acids and calcium , and higher in unsaturated fatty acids , dietary cholesterol and several vitamins . Dietary GI was slightly lower in the Paleolithic diet ( GI = 50 ) than in the Diabetic diet ( GI = 55 ) . Conclusion Over a 3-month study period , a Paleolithic diet improved glycemic control and several cardiovascular risk factors compared to a Diabetes diet in patients with type 2 diabetes . Trial registration Clinical Trials.gov NCT00435240 Higher egg and cholesterol intakes are associated with increased risk of type 2 diabetes mellitus . However , their association with gestational diabetes mellitus ( GDM ) has not been evaluated . The authors assessed such associations in both a prospect i ve cohort study ( 1996 - 2008 ; 3,158 participants ) and a case-control study ( 1998 - 2002 ; 185 cases , 411 controls ) . A food frequency question naire was used to assess maternal diet . Multivariable models were used to derive relative risks and 95 % confidence intervals . Compared with no egg consumption , adjusted relative risks for GDM were 0.94 , 1.01 , 1.12 , 1.54 , and 2.52 for consumption of ≤1 , 2 - 3 , 4 - 6 , 7 - 9 , and ≥10 eggs/week , respectively ( P for trend=0.008 ) . Women with high egg consumption ( ≥7/week ) had a 1.77-fold increased risk compared with women with lower consumption ( 95 % confidence interval ( CI ) : 1.19 , 2.63 ) . The relative risk for the highest quartile of cholesterol intake ( ≥294 mg/day ) versus the lowest ( < 151 mg/day ) was 2.35 ( 95 % CI : 1.35 , 4.09 ) . In the case-control study , the adjusted odds ratio for consuming ≥7 eggs/week versus < 7 eggs/week was 2.65 ( 95 % CI : 1.48 , 4.72 ) , and the odds of GDM increased with increasing cholesterol intake ( P for trend=0.021 ) . In conclusion , high egg and cholesterol intakes before and during pregnancy are associated with increased risk of GDM Carbohydrate-restricted diets ( CRD ) significantly decrease body weight and independently improve plasma triglycerides ( TG ) and HDL cholesterol ( HDL-C ) . Increasing intake of dietary cholesterol from eggs in the context of a low-fat diet maintains the LDL cholesterol (LDL-C)/HDL-C for both hyper- and hypo-responders to dietary cholesterol . In this study , 28 overweight/obese male subjects ( BMI = 25 - 37 kg/m2 ) aged 40 - 70 y were recruited to evaluate the contribution of dietary cholesterol from eggs in a CRD . Subjects were counseled to consume a CRD ( 10 - 15 % energy from carbohydrate ) and they were r and omly allocated to the EGG group [ intake of 3 eggs per day ( 640 mg/d additional dietary cholesterol ) ] or SUB group [ equivalent amount of egg substitute ( 0 dietary cholesterol ) per day ] . Energy intake decreased in both groups from 10,243 + /- 4040 to 7968 + /- 2401 kJ ( P < 0.05 ) compared with baseline . All subjects irrespective of their assigned group had reduced body weight and waist circumference ( P < 0.0001 ) . Similarly , the plasma TG concentration was reduced from 1.34 + /- 0.66 to 0.83 + /- 0.30 mmol/L after 12 wk ( P < 0.001 ) in all subjects . The plasma LDL-C concentration , as well as the LDL-C : HDL-C ratio , did not change during the intervention . In contrast , plasma HDL-C concentration increased in the EGG group from 1.23 + /- 0.39 to 1.47 + /- 0.38 mmol/L ( P < 0.01 ) , whereas HDL-C did not change in the SUB group . Plasma glucose concentrations in fasting subjects did not change . Eighteen subjects were classified as having the metabolic syndrome ( MetS ) at the beginning of the study , whereas 3 subjects had that classification at the end . These results suggest that including eggs in a CRD results in increased HDL-C while decreasing the risk factors associated with BACKGROUND Nutritional therapy is a cornerstone of diabetes management , but no epidemiologic studies have investigated the relation between specific dietary fatty acids and cholesterol and cardiovascular disease ( CVD ) risk among diabetic patients . OBJECTIVE This study assessed the relation between specific dietary fatty acids and cholesterol and CVD risk among women with type 2 diabetes . DESIGN Among 5672 women with type 2 diabetes from the Nurses ' Health Study , diet was assessed prospect ively and up date d periodically . Relative risks of CVD were estimated from Cox proportional hazards analysis after adjustment for potential confounders . RESULTS Between 1980 and 1998 , we identified 619 new cases of CVD ( nonfatal myocardial infa rct ion , fatal coronary heart disease , and stroke ) . The relative risk ( RR ) of CVD for an increase of 200 mg cholesterol/1000 kcal was 1.37 ( 95 % CI : 1.12 , 1.68 ; P = 0.003 ) . Each 5 % of energy intake from saturated fat , as compared with equivalent energy from carbohydrates , was associated with a 29 % greater risk of CVD ( RR : 1.29 ; 95 % CI : 1.02 , 1.63 ; P = 0.04 ) . The ratio of polyunsaturated to saturated fat ( P : S ) was inversely associated with the risk of fatal CVD . We estimated that replacement of 5 % of energy from saturated fat with equivalent energy from carbohydrates or monounsaturated fat was associated with a 22 % or 37 % lower risk of CVD , respectively . CONCLUSIONS A higher intake of cholesterol and saturated fat and a low P : S were related to increased CVD risk among women with type 2 diabetes . Among diabetic persons , replacement of saturated fat with monounsaturated fat may be more effective in lowering CVD risk than is replacement with carbohydrates BACKGROUND A reduction in dietary cholesterol is recommended to prevent cardiovascular disease ( CVD ) . Although eggs are important sources of cholesterol and other nutrients , limited and inconsistent data are available on the effects of egg consumption on the risk of CVD and mortality . OBJECTIVE We aim ed to examine the association between egg consumption and the risk of CVD and mortality . DESIGN In a prospect i ve cohort study of 21,327 participants from Physicians ' Health Study I , egg consumption was assessed with an abbreviated food question naire . Cox regression was used to estimate relative risks . RESULTS In an average follow-up of 20 y , 1550 new myocardial infa rct ions ( MIs ) , 1342 incident strokes , and 5169 deaths occurred . Egg consumption was not associated with incident M \n Output:\n " }, { "from": "agent", "value": "Studies among healthy subjects found suggestive evidence that dietary interventions that include eggs may reduce the risk of T2DM and metabolic syndrome ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: PURPOSE To evaluate safety and efficacy of combined transarterial chemoembolization ( TACE ) with doxorubicin-eluting beads ( DEB ) and sorafenib in patients with advanced hepatocellular carcinoma ( HCC ) . PATIENTS AND METHODS A prospect i ve single-center phase II study was undertaken involving patients with unresectable HCC . The protocol involved sorafenib 400 mg twice per day combined with DEB-TACE . Safety and response were assessed . Results DEB-TACE in combination with sorafenib was successfully administered in 35 patients : mean age , 63 years ; Child 's A , 89 % ; Barcelona Clinic Liver Cancer stage C , 64 % ; Eastern Cooperative Oncology Group performance status of 0 and 1 , 46 % and 54 % , respectively ; and mean index tumor size , 7.7 cm ( st and ard deviation , ± 4.2 cm ) . Patients underwent 128 cycles of therapy ( sorafenib plus DEB-TACE , 60 cycles ; sorafenib alone , 68 cycles ) . Median number of cycles per patient was two ( range , one to five cycles ) ; median number of days treated with sorafenib was 71 ( range , 4 to 620 days ) . The most common toxicities during cycle one were fatigue ( 94 % ) , anorexia ( 67 % ) , alterations in liver enzymes ( 64 % ) , and dermatologic adverse effects ( 48 % ) . Although most patients experienced at least one grade 3 to 4 toxicity , most toxicities were minor ( grade 1 to 2 , 83 % v grade 3 to 4 , 17 % ) . Toxicity during cycle two was decreased . Over the course of the study , there were 40 sorafenib dose interruptions and 25 sorafenib dose reductions . Sorafenib plus DEB-TACE was associated with a disease control rate of 95 % ( Response Evaluation Criteria in Solid Tumors Group)/100 % ( European Association for the Study of the Liver [ EASL ] ) , with an objective response of 58 % ( EASL ) . CONCLUSION The combination of sorafenib and DEB-TACE in patients with unresectable HCC is well tolerated and safe , with most toxicities related to sorafenib . Toxicity is manageable with dose adjustment of sorafenib . Preliminary efficacy data are promising PURPOSE Open-label , phase III trial evaluating whether sunitinib was superior or equivalent to sorafenib in hepatocellular cancer . PATIENTS AND METHODS Patients were stratified and r and omly assigned to receive sunitinib 37.5 mg once per day or sorafenib 400 mg twice per day . Primary end point was overall survival ( OS ) . RESULTS Early trial termination occurred for futility and safety reasons . A total of 1,074 patients were r and omly assigned to the study ( sunitinib arm , n = 530 ; sorafenib arm , n = 544 ) . For sunitinib and sorafenib , respectively , median OS was 7.9 versus 10.2 months ( hazard ratio [ HR ] , 1.30 ; one-sided P = .9990 ; two-sided P = .0014 ) ; median progression-free survival ( PFS ; 3.6 v 3.0 months ; HR , 1.13 ; one-sided P = .8785 ; two-sided P = .2286 ) and time to progression ( TTP ; 4.1 v 3.8 months ; HR , 1.13 ; one-sided P = .8312 ; two-sided P = .3082 ) were comparable . Median OS was similar among Asian ( 7.7 v 8.8 months ; HR , 1.21 ; one-sided P = .9829 ) and hepatitis B-infected patients ( 7.6 v 8.0 months ; HR , 1.10 ; one-sided P = .8286 ) , but was shorter with sunitinib in hepatitis C-infected patients ( 9.2 v 17.6 months ; HR , 1.52 ; one-sided P = .9835 ) . Sunitinib was associated with more frequent and severe adverse events ( AEs ) than sorafenib . Common grade 3/4 AEs were thrombocytopenia ( 29.7 % ) and neutropenia ( 25.7 % ) for sunitinib ; h and -foot syndrome ( 21.2 % ) for sorafenib . Discontinuations owing to AEs were similar ( sunitinib , 13.3 % ; sorafenib , 12.7 % ) . CONCLUSION OS with sunitinib was not superior or equivalent but was significantly inferior to sorafenib . OS was comparable in Asian and hepatitis B-infected patients . OS was superior in hepatitis C-infected patients who received sorafenib . Sunitinib-treated patients reported more frequent and severe toxicity Objective : A phase II study was performed to evaluate the efficacy and tolerability of bevacizumab and erlotinib in advanced hepatocellular carcinoma ( HCC ) patients , and to investigate clinical and molecular predictors of outcome . Methods : 59 patients with advanced HCC received 10 mg/kg i.v . of bevacizumab every 14 days and 150 mg p.o . of erlotinib daily . The primary endpoint was progression-free survival ( PFS ) at 16 weeks . Clinical characteristics and plasma biomarkers expression levels were analyzed . Results : PFS at 16 weeks was 64 % ( 95 % CI 51–76 ) : 14 patients achieved partial response ( 24 % ) , 33 had stable disease ( 56 % ) , 6 progressed ( 10 % ) , and 6 were not evaluable ( 10 % ) . Median overall survival was 13.7 months ( 95 % CI 9.6–19.7 ) , and median PFS was 7.2 months ( 95 % CI 5.6–8.3 ) . Grade 3–4 adverse events included fatigue ( 30 % ) , diarrhea ( 17 % ) , hypertension ( 14 % ) , elevated transaminases ( 12 % ) , and gastrointestinal hemorrhage ( 10 % ) . High plasma angiopoietin-2 , epidermal growth factor receptor , and endothelin-1 , and lack of acneiform rash were associated with poor outcome . Conclusions : The combination of bevacizumab with erlotinib achieved encouraging results in patients with advanced HCC . Current correlatives may help to guide future HCC studies This r and omized , controlled trial assessed the efficacy of transarterial Lipiodol ( Lipiodol Ultrafluide , Laboratoire Guerbet , Aulnay-Sous-Bois , France ) chemoembolization in patients with unresectable hepatocellular carcinoma . From March 1996 to October 1997 , 80 out of 279 Asian patients with newly diagnosed unresectable hepatocellular carcinoma fulfilled the entry criteria and r and omly were assigned to treatment with chemoembolization using a variable dose of an emulsion of cisplatin in Lipiodol and gelatin-sponge particles injected through the hepatic artery ( chemoembolization group , 40 patients ) or symptomatic treatment ( control group , 40 patients ) . One patient assigned to the control group secondarily was excluded because of unrecognized systemic metastasis . Chemoembolization was repeated every 2 to 3 months unless there was evidence of contraindications or progressive disease . Survival was the main end point . The chemoembolization group received a total of 192 courses of chemoembolization with a median of 4.5 ( range , 1 - 15 ) courses per patient . Chemoembolization result ed in a marked tumor response , and the actuarial survival was significantly better in the chemoembolization group ( 1 year , 57 % ; 2 years , 31 % ; 3 years , 26 % ) than in the control group ( 1 year , 32 % ; 2 years , 11 % ; 3 years , 3 % ; P = .002 ) . When adjustments for baseline variables that were prognostic on univariate analysis were made with a multivariate Cox model , the survival benefit of chemoembolization remained significant ( relative risk of death , 0.49 ; 95 % CI , 0.29 - 0.81 ; P = .006 ) . Although death from liver failure was more frequent in patients who received chemoembolization , the liver functions of the survivors were not significantly different . In conclusion , in Asian patients with unresectable hepatocellular carcinoma , transarterial Lipiodol chemoembolization significantly improves survival and is an effective form of treatment Purpose : Vali date d biomarkers of prognosis and response to drug have not been identified for patients with hepatocellular carcinoma ( HCC ) . One of the objectives of the phase III , r and omized , controlled Sorafenib HCC Assessment R and omized Protocol ( SHARP ) trial was to explore the ability of plasma biomarkers to predict prognosis and therapeutic efficacy . Experimental Design : In SHARP , 602 patients with advanced HCC were r and omized to receive either oral sorafenib 400 mg twice a day per os or matching placebo daily on a continuous basis . Ten plasma biomarkers implicated in the pathogenesis of HCC were measured in 491 patients at baseline and in 305 after 12 weeks of treatment . The c and i date biomarkers were analyzed to identify correlates of prognosis or predictors of response to sorafenib . Results : In both the entire patient population and the placebo cohort , baseline angiopoietin 2 ( Ang2 ) and VEGF concentrations independently predicted survival . Clinical variables such as macroscopic vascular invasion , Eastern Cooperative Oncology Group ( ECOG ) performance status , and baseline α-fetoprotein and alkaline phosphatase concentrations also independently predicted survival in these groups . In the sorafenib cohort , trends toward enhanced survival benefit from sorafenib were observed in patients with high s-c-KIT or low hepatocyte growth factor concentration at baseline ( P of interaction = 0.081 and 0.073 , respectively ) . Conclusions : The angiogenesis biomarkers Ang2 and VEGF were independent predictors of survival in patients with advanced HCC . In contrast , none of the biomarkers tested significantly predicted response to sorafenib . Clin Cancer Res ; 18(8 ) ; 2290–300 . © 2012 AACR UNLABELLED Angiogenesis inhibition by the vascular endothelial growth factor receptor ( VEGFR ) and platelet-derived growth factor receptor ( PDGFR ) inhibitor sorafenib provides survival benefit in hepatocellular carcinoma ( HCC ) ; however , angiogenic escape from sorafenib may occur due to angiogenesis-associated fibroblast growth factor receptor ( FGFR ) pathway activation . In addition to VEGFR and PDGFR , dovitinib inhibits FGFR . Frontline oral dovitinib ( 500 mg/day , 5 days on , 2 days off ; n = 82 ) versus sorafenib ( 400 mg twice daily ; n = 83 ) was evaluated in an open-label , r and omized phase 2 study of Asian-Pacific patients with advanced HCC . The primary and key secondary endpoints were overall survival ( OS ) and time to tumor progression ( TTP ) as determined by a local investigator , respectively . Patients included in the study were ineligible for surgical and /or locoregional therapies or had disease progression after receiving these therapies . The median OS ( 95 % confidence interval [ CI ] ) was 8.0 ( 6.6 - 9.1 ) months for dovitinib and 8.4 ( 5.4 - 11.3 ) months for sorafenib . The median TTP ( 95 % CI ) per investigator assessment was 4.1 ( 2.8 - 4.2 ) months and 4.1 ( 2.8 - 4.3 ) months for dovitinib and sorafenib , respectively . Common any-cause adverse events included diarrhea ( 62 % ) , decreased appetite ( 43 % ) , nausea ( 41 % ) , vomiting ( 41 % ) , fatigue ( 35 % ) , rash ( 34 % ) , and pyrexia ( 30 % ) for dovitinib and palmar-plantar erythrodysesthesia syndrome ( 66 % ) and decreased appetite ( 31 % ) for sorafenib . Subgroup analysis revealed a significantly higher median OS for patients in the dovitinib arm who had baseline plasma soluble VEGFR1 ( sVEGFR1 ) and hepatocyte growth factor ( HGF ) below median levels versus at or above the median levels ( median OS [ 95 % CI ] : sVEGFR1 , 11.2 [ 9.0 - 13.8 ] and 5.7 [ 4.3 - 7.0 ] months , respectively [ P = .0002 ] ; HGF , 11.2 [ 8.9 - 13.8 ] and 5.9 [ 5.0 - 7.6 ] months , respectively [ P = 0.0002 ] ) . CONCLUSION Dovitinib was well tolerated , but activity was not greater than sorafenib as a frontline systemic therapy for HCC . Based on these data , no subsequent phase 3 study has been planned . ( Hepatology 2 \n Output:\n " }, { "from": "agent", "value": "In first-line therapy , patients receiving sorafenib had increased overall survival and progression free survival ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Arginine is a common substrate for the synthesis of nitric oxide and polyamines that are crucial for placental angiogenesis and growth in mammals . This study was conducted to test the hypothesis that dietary l-arginine supplementation may improve reproductive performance of pregnant gilts . Fifty-two pregnant gilts with body weight ( BW ) of 166.3 + /- 1.8 kg were housed individually in gestation crates . At d 30 of gestation , gilts were assigned r and omly to corn-soybean-based diets supplemented with 1.0 % L-arginine-HCl or 1.7 % L-alanine ( isonitrogenous control ) . Both diets contained 13.0 MJ metabolizable energy/kg and 12.2 % crude protein and were fed to gilts at 1 kg twice daily during gestation . Backfat thickness and BW were measured and blood sample s were obtained on 30 , 70 , 90 , and 110 d of gestation . At d 110 of gestation , gilts were transferred to individual farrowing crates . The numbers of total piglets born and born alive , as well as birth weights of piglets , were recorded immediately after farrowing . Throughout the gestation , BW or backfat thickness of gilts did not differ between treatment groups . Plasma urea concentrations were lower in arginine-supplemented than in control gilts at d 90 ( P < 0.010 ) and d 110 ( P < 0.001 ) of gestation . Compared with the control group , arginine supplementation increased the number of pigs born alive by 22 % ( 11.40 vs. 9.37 , P = 0.032 ) and live litter birth weight of piglets by 24 % ( 16.38 vs. 13.19 kg , P = 0.016 ) . This exciting finding provides the first evidence for a marked increase of live-born piglets by 2 per litter through nutritional intervention in gilts The effects of l-arginine on porcine foetal development and myogenesis were determined . Twenty Swiss Large White gilts were r and omly allocated to either the control ( C ) or l-arginine treatment ( A ) . In addition to the st and ard gestation diet , A-sows received 26 g l-arginine daily from days 14 to 28 of gestation . At day 75 of pregnancy , sows were sacrificed and the number and weight of foetuses were recorded . From each litter , the lightest , heaviest and the ones with an average foetal weight ( FtW ) were selected . Primary ( P ) , secondary ( S ) and total myofiber number as well as S/P ratio were determined in the semitendinosus ( ST ) and rhomboideus ( RH ) muscles . In A-sows , the number of viable foetuses ( 13.0 v. 9.3 ) and total FtW ( 4925 v. 3729 g ) was greater ( P ⩽ 0.04 ) than in C-sows . Compared to C-sow foetuses , the ST of A-sow foetuses had 7 % more ( 17 699 v. 16 477 ; P = 0.04 ) P myofibers and the S/P ratio in both muscles was lower ( ST = 20.3 v. 21.5 ; RH = 24.1 v. 27.1 ; P ⩽ 0.07 ) . Regardless of the maternal diet , the S myofiber number and the S/P ratio in both muscles were greater ( P ⩽ 0.01 ) in foetuses with a high FtW compared to low FtW. These data suggest that l-arginine supplemented to gilts during early gestation enhanced foetal survival and in the ST positively affected the primary phase of myofiber formation Placental vascular formation and blood flow are crucial for fetal survival , growth and development , and arginine regulates vascular development and function . This study determined the effects of dietary arginine or N-carbamylglutamate ( NCG ) supplementation during late gestation of sows on the microRNAs , vascular endothelial growth factor A ( VEGFA ) and endothelial nitric oxide synthase ( eNOS ) expression in umbilical vein . Twenty-seven l and race × large white sows at day ( d ) 90 of gestation were assigned r and omly to three groups and fed the following diets : a control diet and the control diet supplemented with 1.0 % l-arginine or 0.10 % NCG . Umbilical vein of fetuses with body weight around 2.0 kg ( oversized ) , 1.5 kg ( normal ) and 0.6 kg ( intrauterine growth restriction , IUGR ) were obtained immediately after farrowing for miR-15b , miR-16 , miR-221 , miR-222 , VEGFA and eNOS real-time PCR analysis . Compared with the control diets , dietary Arg or NCG supplementation enhanced the reproductive performance of sows , significantly increased ( P < 0.05 ) plasma arginine and decreased plasma VEGF and eNOS ( P < 0.05 ) . The miR-15b expression in the umbilical vein was higher ( P < 0.05 ) in the NCG-supplemented group than in the control group . There was a trend in that the miR-222 expression in the umbilical vein of the oversized fetuses was higher ( 0.05 < P < 0.1 ) than in the normal and IUGR fetuses . The expression of eNOS in both Arg-supplemented and NCG-supplemented group were lower ( P < 0.05 ) than in the control group . The expression of VEGFA was higher ( P < 0.05 ) in the NCG-supplemented group than in the Arg-supplemented and the control group . Meanwhile , the expression of VEGFA of the oversized fetuses was higher ( P < 0.05 ) than the normal and IUGR fetuses . In conclusion , this study demonstrated that dietary Arg or NCG supplementation may affect microRNAs ( miR-15b , miR-222 ) targeting VEGFA and eNOS gene expressions in umbilical vein , so as to regulate the function and volume of the umbilical vein , provide more nutrients and oxygen from the maternal to the fetus tissue for fetal development and survival , and enhance the reproductive performance of sows Suboptimal embryonic/fetal survival and growth remains a significant problem in mammals . Using a swine model , we tested the hypothesis that dietary l-arginine supplementation during gestation may improve pregnancy outcomes through enhancing placental growth and modulating hormonal secretions . Gestating pigs ( Yorkshire × L and race , n = 108 ) were assigned r and omly into two groups based on parity and body weight , representing dietary supplementation with 1.0 % l-arginine – HCl or 1.7 % l-alanine ( isonitrogenous control ) between days 22 and 114 of gestation . Blood sample s were obtained from the ear vein on days 22 , 40 , 70 and 90 of gestation . On days 40 , 70 and 90 of gestation , concentrations of estradiol in plasma were higher ( P < 0.05 ) in arginine-supplemented than in control sows . Moreover , arginine supplementation increased ( P < 0.05 ) the concentrations of arginine , proline and ornithine in plasma , but concentrations of urea or progesterone in plasma did not differ between the two groups of sows . Compared with the control , arginine supplementation increased ( P < 0.05 ) the total number of piglets by 1.31 per litter , the number of live-born piglets by 1.10 per litter , the litter birth weight for all piglets by 1.36 kg , and the litter birth weight for live-born piglets by 1.70 kg . Furthermore , arginine supplementation enhanced ( P < 0.05 ) placental weight by 16.2 % . The weaning-to-estrus interval of sows was not affected by arginine supplementation during gestation . These results indicate that dietary arginine supplementation beneficially enhances placental growth and the reproductive performance of sows The present study characterised gene expression associated with embryonic muscle development and placental vascularisation during early gestation in the pig and examined effects of Progenos supplementation in early pregnancy . Tissues were collected from commercial multiparous sows ( n = 48 ) from Days 16 to 49 of gestation . In the placenta , qPCR revealed that vascular endothelial growth factor ( VEGFA ) expression did not change from Day 17 to 49 of gestation ; however , KDR receptor and angiopoietin-1 and -2 expression were differentially regulated , with periods of high expression corresponding to two critical phases of angiogenesis in the pig . In the embryo , the pattern of myogenesis-related gene expression was consistent with available literature . A commercially available nutritional supplement Progenos ( 20 g day⁻¹ L-arginine ) added to the diet of sows from either Day 15 to 29 ( P15 - 29 ; n = 33 ) , Day 30 to 44 ( n = 29 ) or from Day 15 to 44 ( n = 76 ) of gestation tended to increase ( P = 0.058 ) embryonic growth rate compared with non-supplemented controls ( n = 79 ) and angiogenin expression was higher ( P = 0.028 ) at Day 30 of gestation in placentae from sows on the P15 - 29 Progenos treatment . These results are consistent with proposed beneficial effects of l-arginine on early embryonic development and placental vascularisation A 2 x 2 factorial arrangement of treatments in a r and omized block design was used to determine the effects of dietary Arg supplementation during gestation and lactation on the lactation performance of 38 first-parity sows . At 30 d of gestation , pregnant gilts were allotted based on BW to 1 of 2 diets supplemented with 1 % L-Arg . HCl or 1.7 % L-Ala ( isonitrogenous control ) . After farrowing , sows were further allotted based on BW within previous gestation treatment groups to 1 of 2 lactation diets supplemented with 1 % L-Arg . HCl or 1.7 % L-Ala ( isonitrogenous control ) . All gestation diets contained 3.1 Mcal/kg and 12.2 % CP ( as is ) and were fed 2 kg/d in 2 equally sized meals , whereas all lactation diets contained 3.2 Mcal/kg and 18.6 % CP ( as is ) and were fed ad libitum . Litter size was st and ardized to 10 piglets by cross-fostering within 24 h postfarrowing . On a weekly basis , BW and backfat ( BF ) thickness of sows , as well as piglet BW were measured , and blood and milk sample s were obtained from the sows . Number of days from weaning to estrus and ADFI were also recorded . There were no differences in BW , BF thickness , ADFI , or days until return to estrus among treatment groups . There was no effect of the gestation diet or a gestation x lactation diet interaction on any parameter measured . On d 7 of lactation , plasma concentrations of Arg and insulin in sows , as well as concentrations of most AA in milk , were greater ( P < 0.05 ) in response to Arg supplementation during lactation compared with the control . Weight gain of piglets from sows fed the Arg-supplemented diet during lactation was greater between d 0 and 7 ( P < 0.01 ) and between d 0 and 21 ( P < 0.05 ) of lactation compared with piglets from sows fed the control diet . Collectively , results from this study indicate the potential beneficial effects of dietary Arg supplementation in improving the lactation performance of first-parity sows Preweaning piglet mortality is largely attributed to the incidence of low birth weight and birth weight variation within the litter . Therefore , developing strategies to increase within-litter uniformity of piglet birth weight is important . This study investigated the effects of different feeding strategies based on specific nutrient supplies in sow diet on the within-litter variation of piglet birth weight ( BW0 ) . Four batches of highly prolific crossbred L and race × Large White sows were used . Three dietary treatments were compared : supplies of dextrose during the week before insemination ( 190 g/d ) and of L-arginine ( 25.5 g/d ) from d 77 of pregnancy until term ( DEXA , n = 26 ) ; a dietary supplementation of L-arginine only ( 25.5 g/d ) , from d 77 of pregnancy until term ( ARGI , n = 24 ) ; and no supplementation to a st and ard gestation diet ( CTL ; n = 23 ) . Total born piglets ( TB ) , i.e. , piglets born alive ( BA ) and stillborn piglets , were numbered and weighed at birth and at weaning . Data were analyzed by ANOVA using the MIXED procedure in a model that included dietary treatment ( ARGI , DEXA , and CTL ) , initial parity ( 1 , 2 and 3 , 4 , and more \n Output:\n " }, { "from": "agent", "value": "It is concluded that supplementing dietary arginine in gestating sows can benefit embryo survival and foetal development ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: OBJECTIVE To compare the performance and acceptability of 2 types of female condoms ( FCs ) among female sex workers ( FSWs ) in China . METHODS The present crossover survey trial was conducted in Enping City between September and December 2007 . RESULTS There were no significant differences between the 2 types of condoms in cumulative rates of episodes of misdirection ; participants experiencing discomfort or feeling the outer or inner ring of an FC ; or the clinical breakage or turning inside out of an FC . The rates of total clinical failures were similar for both FC types . Moreover , 59.5 % of the survey participants reported that either type was acceptable to them . CONCLUSION There were no statistically significantly differences in performance between the 2 types of FCs tested , and most participants would accept using either in the future BACKGROUND New design s of female condom have been developed to reduce costs and improve acceptability . To secure regulatory approvals , clinical studies are needed to verify performance . We aim ed to assess the functional performance and safety of three new condom types-the Woman 's Condom , the VA worn-of-women ( wow ) Condom Feminine , and the Cupid female condom-against the existing second-generation female condom ( FC2 ) . METHODS We did a r and omised controlled , non-inferiority , four-period crossover trial at three sites in Shanghai , China , and one site in Durban , South Africa , between May 1 , 2011 , and Jan 31 , 2012 . Participants aged 18 - 45 years who were sexually active , monogamous , not pregnant , and not sex workers , were eligible for inclusion if they were literate , had no known allergies to the study products ; used a reliable , non-barrier method of contraception , and had no visible or reported sexually transmitted infections . We used a computer-generated r and omisation sequence with a Williams square design of size four to assign patients ( 1:1:1:1 ) to the FC2 control device , or the Woman 's , VA wow , or Cupid condoms , with 12 potential allocations . R and omisation was stratified by site . Participants were not masked to condom type , but allocation was concealed from study investigators . The primary non-inferiority endpoints were total clinical failure and total female condom failure , with a non-inferiority margin of 3 % . Women were asked to use five of each condom type and were interviewed after use of each type . We also assessed safety data for each type . We did both per- protocol and intention-to-treat analyses . We calculated frequencies and percentages for each failure event and estimated differences in performance with a generalised estimating equation model . This study is registered , number DOH-27 - 0113 - 4271 . FINDINGS 616 women were assessed for eligibility , of whom 600 were r and omly assigned to condom-type order ( 30 , 120 , and 150 women in the three sites in China , and 300 women in the site in South Africa ) . 572 women completed follow-up , with at least one condom of each type . Total female condom failure was 3·43 % for FC2 , 3·85 % for the Woman 's Condom ( difference 0·42 % , 90 % CI -1·42 to 2·26 ) , 3·02 % for VA wow ( -0·42 % , -1·86 to 1·32 ) , and 4·52 % for Cupid ( 1·09 % , -0·60 to 2·78 ) ; total clinical failure was 2·88 % , 3·05 % ( 0·17 % , -1·48 to 1·81 ) , 2·49 % ( -0·25 % , -1·75 to 1·26 ) , and 3·87 % ( 0·99 % , -0·55 to 2·52 ) , respectively . Only two ( < 1 % ) participants , in South Africa , reported serious adverse events , unrelated to use of the study products . INTERPRETATION Non-inferiority was shown for all condom failure events for the three new devices versus the FC2 , within the predefined margin . FUNDING Universal Access to Female Condoms ( UAFC ) Objective To measure the impact on sexually transmitted infection ( STI ) prevalence of a female condom introduction and risk-reduction program at Kenyan agricultural sites . Design We conducted a cluster-r and omized trial to determine whether a replicable , community-level intervention would reduce STI prevalence . Methods Six matched pairs of tea , coffee and flower plantations were identified . The six intervention sites received an information/motivation program with free distribution of female and male condoms , and six control sites received only male condoms and related information . Participants were tested for cervical gonorrhea and chlamydia by ligase chain reaction on urine specimens , and vaginal trichomoniasis by culture , at baseline , 6 and 12 months . Results Participants at intervention ( n = 969 ) and control sites ( n = 960 ) were similar ; baseline STI prevalence was 23.9 % . Consistent male condom use was more than 20 % at 12 months . Consistent female condom use was reported by 11 and 7 % of intervention site women at 6 and 12 months . Unadjusted STI prevalence was 16.5 and 17.4 % at 6 months , and 18.3 and 18.5 % at 12 months , at the intervention and control sites , respectively . Logistic regression models confirmed the null effect of the female condom intervention . Conclusions Female condom introduction did not enhance STI prevention at these sites . It is unclear which aspects of the intervention – STI education , condom promotion , case management – were associated with decreased STI prevalence from baseline to follow-up In this 2000 - 2001 study , the authors compared the effectiveness of the male latex condom and the female polyurethane condom by assessing frequency and types of mechanical failure and by evaluating semen exposure during use . Eligible women from Birmingham , Alabama , were r and omly assigned to begin the study with 10 male condoms and then switch to 10 female condoms ( n = 55 ) , or vice versa ( n = 53 ) , and were trained to use both types . Data collection included question naires for each condom use and measurement of prostate-specific antigen in specimens of vaginal fluid taken before and after intercourse . Participants returned 700 male condoms and 678 female condoms , and they reported mechanical problems for 9 % and 34 % , respectively . Moderate-high postcoital prostate-specific antigen levels ( > or = 22 ng/ml ) were detected in 3.5 % of male condom uses and 4.5 % of female condom uses ( difference = 1 % , 95 % confidence interval : -1.6 , 3.7 ) . Moderate-high prostate-specific antigen values ( > or = 22 ng/ml ) were more frequent with mechanical problems ( male condom , 9.6 % ; female condom , 9.4 % ) but less frequent with other problems ( 3.0 % and 0.9 % ) or correct use with no problems ( 2.7 % and 2.5 % ) . This study indicates that although mechanical problems are more common with the female condom than with the male condom , these devices may involve a similar risk of semen exposure . Objective ly assessed semen exposure is associated with self-reported mechanical problems BACKGROUND The widespread distribution of female condoms ( FCs ) in developing countries has been hindered by high unit cost , making new less expensive devices a priority for donor agencies . STUDY DESIGN R and omized , crossover study assessing product preference , safety , acceptability and function of three new FCs ( PATH Woman 's Condom , FC2 and V-Amour ) among 170 women in Durban , South Africa . A subsequent \" simulated market \" study provided participants with free choice of FCs and assessed condom uptake over 3 months . RESULTS Of the 160 women who used at least one FC of each type , 47.5 % preferred the PATH Woman 's Condom ( WC ) , 35.6 % preferred FC2 and 16.3 % preferred V-Amour ( p<.001 ) . Women rated the WC better than FC2 and V-Amour for appearance , ease of use and overall fit and better than V-Amour for feel . WC was rated worse than FC2 and V-Amour for lubrication volume . The simulated market demonstrated similar preferences . Total clinical failure rates ( i.e. , the types of failures that could result in pregnancy or STI ) were low ( < 4 % ) , regardless of condom type . CONCLUSIONS Three new FC types functioned similarly and were generally acceptable . Most participants preferred WC and FC2 over V-Amour , and WC was preferred over FC2 in several acceptability measures Background : Few studies have measured female condom use for more than a 6‐month period or among persons at high risk of STD . Objective : To measure long‐term use of the female condom among couples at high risk of HIV infection and to evaluate the effect of female condom use on unprotected coital acts . Study Design : Ninety‐nine Zambian couples with symptomatic sexually transmitted diseases ( STD ) received female condoms , male condoms , and spermicides and were counseled to use either condom plus spermicide for each coital act . Couples were followed up at 3‐ , 6‐ , and 12‐month visits . Barrier contraceptive use was measured prospect ively by coital log . Results : Among the 99 couples enrolled , 51 , 38 , and 30 couples were successfully followed up for 3 , 6 , and 12 months , respectively . Female condoms were reportedly used in 24 % , 27 % , and 23 % of coital acts and by 86 % , 79 % , and 67 % of the returning couples during each time interval . Higher‐level female condom users used male condoms less often but had fewer unprotected coital acts ( 5 % vs. 14 % ; p < 0.05 ) than lower‐level female condom users . Conclusion : A majority of couples at high risk of HIV infection used the female condom in conjunction with other barrier methods over a 1‐year period . The addition of female condoms accompanied by appropriate counseling to the barrier method mix may reduce unprotected sex among couples at high‐risk of HIV infection STUDY OBJECTIVE : To compare the association between different measures of condom use and prevalent HIV infection . DESIGN : R and omised cross sectional study to assess association between HIV infection and different measures of self reported condom use . Female sex workers were r and omised to one of five different face to face question naires on condom use . Three question naires used always to never scales to measure use but differed in the reference period for use ; a fourth asked about use in the last 10 coital acts ; and the fifth was a retrospective log of coital acts in the past two weeks . Use was assessed with new clients , repeat clients , and non-clients . SETTING : Yaoundé and Douala , Cameroon . PARTICIPANTS : 2266 female sex workers . MAIN RESULTS : The association between condom use and prevalent HIV infection varied for different measures of condom use . None of the five level measures showed a dose response protective effect of condom use . Measures aim ed at reducing recall bias ( measures based on the past 10 coital acts or a coital log ) showed little or no association with prevalent infection . Measures based on the past month or six months had a stronger association with prevalent infection . Regardless of the type of measure or reference period , the strongest association between use and infection was for use with partners who were not clients . CONCLUSION : These findings underscore challenges described by others of measuring condom use and interpreting the association between use and prevalent infection CONTEXT Whereas the female condom has been evaluated in many hypothetical acceptability or short-term use studies , there is little information about its suitability for the prevention of sexually transmitted diseases ( STDs ) or HIV over extended periods of time . METHODOLOGY As part of a six-month prospect i ve follow-up study of 1,159 STD clinic patients , clients were interviewed during their initial visit , exposed to a behavioral intervention promoting condoms , given a physical examination and provided with instructions on completing a sexual diary . Potential predictors of trying the female condom were evaluated using logistic regression , and three condom-use groups ( exclusive users of female condoms , exclusive users of male condoms and users of both types of condoms ) were compared using multinomial regression . RESULTS Among 895 women who reported having engaged in vaginal intercourse during the study period , one-half had sex with only one partner , while one-quarter each had two partners or three or more partners . A total of 731 women reported using the female condom at least once during the follow-up period--85 % during the first month of follow-up . Multiple logistic regression analyses indicated that employed women and those with a regular sexual partner at baseline were significantly more likely to try the female condom . By the end of the follow-up period , 8 % of participants had used the female condom exclusively , 15 % had used the male condom exclusively , 73 % had used both types of condom and 3 % had used no condoms . Twenty percent of women who tried the female condom used it only once and 13 % used it twice , while 20 % used 5 - 9 female condoms and 32 % used 10 or more . Consistent condom users ( N=309 ) were predominantly users of both types of condom ( 75 % ) , and were less often exclusive users of the male condom ( 18 % ) or the female condom ( 7 % ) . According to a multivariate analysis , women who used the female condom exclusively or who mixed condom types were more likely to be black , were more likely to \n Output:\n " }, { "from": "agent", "value": "The use of female plus male condoms is more effective than use of male condoms only in preventing STIs and may be as effective as the male condom only in preventing HIV ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Recent evidence suggests that dietary fat intake may be more strongly associated than total energy intake to the development and maintenance of obesity . The objective of this study was to determine whether dietary fat restriction would promote more favorable changes in body weight , body composition , resting metabolic rate ( RMR ) , eating behavior , and dietary adherence than calorie restriction . Sixty-five obese women and 15 obese men were recruited and r and omly assigned to calorie restriction ( 1000–1200 kcal/day ) or fat restriction ( 22–26 g/day ) . Subjects participated in a 24-week behavioral weight loss program . Fortyeight subjects completed assessment s at all four time points — baseline and 6 , 12 , and 18 months . Weight loss was significantly greater in the low calorie ( LC ) group ( −11.2 versus −6.1 kg , p<.001 ) and was maintained better at the 18-month assessment ( −7.5 versus −1.8 kg , p≤.001 ) . There was a significantly greater decrease in percent body fat and RMR for the LC group with only percent body fat still significantly lower at 18 months . Subjects in the LC group consumed significantly fewer calories , less carbohydrates , and the same amount of fat as those in the low fat ( LF ) condition , however , calorie and carbohydrate intake were decreasing for LF subjects by the 12- and 18-month assessment s. There were no long-term differences in most measured predictors of dietary adherence . Dietary fat restriction did not prove to be superior to calorie restriction , thus strengthening the public health message that calories do count The role of dietary fat in the regulation of energy intake was assessed by manipulating a conventional diet and measuring spontaneous food consumption . Twenty-four women each consumed a sequence of three 2-wk dietary treatments in which 15 - 20 % , 30 - 35 % , or 45 - 50 % of the energy was derived from fat . These diets consisted of foods that were similar in appearance and palatability but differed in the amount of high-fat ingredients used . Relative to their energy consumption on the medium-fat diet , the subjects spontaneously consumed an 11.3 % deficit on the low-fat diet and a 15.4 % surfeit on the high-fat diet ( p less than 0.0001 ) , result ing in significant changes in body weight ( p less than 0.001 ) . A small amount of caloric compensation did occur ( p less than 0.02 ) , which was greatest in the leanest subjects ( p less than 0.03 ) . These results suggest that habitual , unrestricted consumption of low-fat diets may be an effective approach to weight control In a prospect i ve , r and omised , controlled trial to determine whether comprehensive lifestyle changes affect coronary atherosclerosis after 1 year , 28 patients were assigned to an experimental group ( low-fat vegetarian diet , stopping smoking , stress management training , and moderate exercise ) and 20 to a usual-care control group . 195 coronary artery lesions were analysed by quantitative coronary angiography . The average percentage diameter stenosis regressed from 40.0 ( SD 16.9)% to 37.8 (16.5)% in the experimental group yet progressed from 42.7 (15.5)% to 46.1 (18.5)% in the control group . When only lesions greater than 50 % stenosed were analysed , the average percentage diameter stenosis regressed from 61.1 (8.8)% to 55.8 (11.0)% in the experimental group and progressed from 61.7 (9.5)% to 64.4 (16.3)% in the control group . Overall , 82 % of experimental-group patients had an average change towards regression . Comprehensive lifestyle changes may be able to bring about regression of even severe coronary atherosclerosis after only 1 year , without use of lipid-lowering drugs This r and omised controlled trial examined anthropometric changes and cardiovascular benefits of six months of weight management in 110 free living women , aged 18–68 y and BMI 25–50 kg/m2 , who received 1200 kcal/d diet treatments of either high ( 58 % energy , n=57 ) or low ( 35 % energy , n=53 ) carbohydrate ( CHO ) content . Body weight , plasma total , HDL and LDL cholesterol , triglyceride and blood pressure were measured . Examination at three months showed women on high CHO lost ( mean±s.e.m . ) 4.3±0.5 kg and those on low CHO lost 5.6±0.6 kg of body weight . Changes in risk factors did not significantly differ between the two diet treatments throughout the study . However those on high CHO diets significantly lowered their plasma total cholesterol by 0.33 mmol/l ( 95 % CI : 0.10 , 0.55 ) , LDL cholesterol by 0.23 mmol/l ( 0.02 , 0.43 ) and HDL cholesterol by 0.05 mmol/l ( 0.03 , 0.10 ) , while women on low CHO diets lowered only plasma triglyceride by 0.28 mmol/l ( 0.08 , 0.48 ) . Blood pressure did not change significantly on either diet . After six months , women on high CHO lost 5.6±0.8 kg and those on low CHO lost 6.8±0.8 kg . On the high CHO diet , total cholesterol remained significantly below the baseline value at 0.34 mmol/l ( 0.13 , 0.56 ) , triglyceride was significantly lowered by 0.27 mmol/l ( 0.10 , 0.45 ) , and HDL cholesterol returned to the baseline value . On the low CHO diet , triglyceride remained the only risk factor to be significantly improved . A subgroup of 46 postmenopausal women lost significantly ( P<0.05 ) more weight on the low CHO diet than high CHO diet . In conclusion , these results provided some support for preferring a high CHO diet to a lower CHO approach in weight management , from the point of view of risk reduction , but do not indicate a consistently more rapid weight loss with either diet OBJECTIVE The aim of this r and omized trial was to compare the effects of a behavioral intervention focusing on either calorie restriction alone or calorie plus fat restriction on weight loss and changes in lipids and glycemic control in individuals with non-insulin-dependent diabetes mellitus ( NIDDM ) or a family history of diabetes . RESEARCH DESIGN AND METHODS We recruited 44 obese women with NIDDM and 46 obese women with a family history of NIDDM and r and omly assigned these subjects to calorie restriction ( CAL ) or to calorie plus fat restriction ( CAL + FAT ) . All subjects participated in a 16-week behavioral weight loss program , with training in diet , exercise , and behavior modification . Subjects assigned to the CAL condition were given a 1,000−1,500 kcal/day goal and self-monitored calories consumed . Subjects assigned to the CAL + FAT condition had the same calorie goal , but were also given a fat goal ( grams of fat/day ) , to produce a diet with < 20 % of calories from fat ; this group monitored both calories and fat grams . RESULTS Among NIDDM subjects , weight loss of the subjects in the CAL+FAT condition was significantly > subjects in the CAL condition ( 7.7 vs. 4.6 kg ) and the CAL+FAT condition group also maintained their weight loss better at the 1-year follow-up ( 5.2 vs. 1.0 kg ) . Significant decreases in glucose , high-density lipoprotein ( HDL ) cholesterol , and total cholesterol were seen after 16 weeks of treatment among NIDDM subjects ; these changes were similar in CAL and CAL+FAT groups , but a greater proportion of subjects in CAL condition required oral hypoglycemic medication . At the 1-year follow-up , all parameters had returned to baseline . No significant differences in weight loss or physiological changes were seen between CAL and CAL+FAT conditions in subjects with a family history of diabetes . CONCLUSIONS These results suggest that using the combination of calorie and fat restriction may help promote weight loss in obese NIDDM patients . No other long-term benefits of this regimen were observed OBJECTIVE : We investigated the prevalence of overweight and obesity and their relationships with the main cardiovascular risk factors in the population of Ventimiglia di Sicilia , a rural village in Southern Italy characterized by low cholesterol levels and by a low incidence of early coronary heart disease mortality . We related all deaths to body weight and fat distribution during an 8 y follow-up . DESIGN : Cross-sectional and prospect i ve observational study .SUBJECTS : A total of 835 free-living individuals , 363 males and 472 females , of age between 20 and 69 y. MEASUREMENTS : In all participants body weight , waist-to-hip ratio ( WHR ) , cardiovascular risk factors and plasma lipids were measured . During the follow-up , total and cardiovascular deaths were registered . RESULTS : We found a high overall prevalence of subjects with overweight or obesity ( respectively 45.0 % and 27.7 % ) , with great differences among classes of age . As expected , body weight and fat distribution were associated with diabetes , hypertension , dyslipidemia and with a worsening of lipid profile . During the follow-up we registered 37 total and 11 cardiovascular deaths . All-cause and cardiovascular mortality risks were , respectively , 1.64 ( 95 % CI 0.65–4.15 ) and 2.71 ( 95 % CI 0.29–25.26 ) in subjects with a body mass index ( BMI ) of 27–29.99 kg/m2 and 2.45 ( 95 % CI 1.03–5.87 ) and 5.36 ( 95 % CI 1.41–62.01 ) in subjects with a BMI of≥30 kg/m2 in comparison with participants with a BMI of < 27 kg/m2 , and 3.48 ( 95 % CI 1.46–8.30 ) and 4.55 ( 95 % CI 1.12–18.40 ) in subjects with a WHR higher than the median in comparison with individuals with a WHR lower than the median . CONCLUSION : The Ventimiglia di Sicilia Study highlights the great importance of overweight and obesity as a public health issue in a rural population and indicates that it is necessary to consider the impact of body weight and fat distribution on both total and CHD mortality Quantification of the excess mortality from all causes associated with obesity remains controversial . In this paper , 6,193 obese patients , those with a body mass index ( weight (kg)/height (m)2 ( BMI ) ) range of 25 - 74 kg/m2 , recruited from 1961 to 1994 in Düsseldorf , Germany , were followed for a mean time of 14 ( st and ard deviation , 8.2 ) years , yielding 87,179 observed patient-years . During the study period , 1,028 patients ( 16.6 % ) died . The entire cohort was grouped into approximate quartiles according to BMI : group 1 , BMI from 25 to < 32 ; group 2 , BMI from 32 to < 36 ; group 3 , BMI from 36 to < 40 ; group 4 , BMI > or = 40 kg/m2 . The following risk ratios were estimated by means of Cox proportional hazards models using the lowest BMI group as reference category : group 2 for men , 1.02 ( 95 % confidence interval 0.76 - 1.37 ) ; for women , 1.23 ( 95 % confidence interval 0.96 - 1.58 ) ; group 3 for men , 1.50 ( 95 % confidence interval 1.09 - 2.06 ) ; for women , 1.33 ( 95 % confidence interval 1.03 - 1.73 ) ; and group 4 for men , 2.10 ( 95 % confidence interval 1.53 - 2.88 ) ; for women , 2.25 ( 95 % confidence interval 1.78 - 2.84 ) . The following st and ardized mortality ratios were calculated by using the respective geographic area ( the Federal State of North Rhine Westphalia ) as reference population : group 1 for men , 1.26 ( 95 % confidence interval 0.98 - 1.61 ) ; for women , 1.00 ( 95 % confidence interval 0.81 - 1.23 ) ; group 2 for men , 1.31 ( 95 % confidence interval 1.09 - 1.57 ) ; for women , 1.20 ( 95 % confidence interval 1.02 - 1.40 ) ; group 3 for men , 1.92 ( 95 % confidence interval 1.53 - 2.38 ) ; for women , 1.27 ( 95 % confidence interval 1.07 - 1.50 ) ; and group 4 for men , 3.05 ( 95 % confidence interval 2.47 - 3.73 ) ; for women , 2.31 ( 95 % confidence interval \n Output:\n " }, { "from": "agent", "value": "Apart from one study which showed a slight but statistically significant difference in total cholesterol in the low fat group at one year follow-up , there were no significant differences between the dietary groups for other outcome measures such as serum lipids , blood pressure and fasting plasma glucose .\nREVIEW ER 'S CONCLUSIONS The review suggests that fat-restricted diets are no better than calorie restricted diets in achieving long term weight loss in overweight or obese people .\nOverall , participants lost slightly more weight on the control diets but this was not significantly different from the weight loss achieved through dietary fat restriction and was so small as to be clinical ly insignificant" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Objective : To investigate whether additional early physiotherapy after stroke improved functional recovery in stroke patients . Design : A prospect i ve , r and omized , controlled study . Setting : One stroke ward and an acute stroke unit in a large teaching hospital , southern China . Subjects : Patients with first-onset stroke consecutively admitted to the stroke centre . Interventions : One group ( n = 78 ) received additional early physiotherapy ( AEP ) for 45 minutes , five days a week for four weeks starting within the first week since stroke onset ; the routine therapy ( RT ) group ( n = 78 ) received no professional rehabilitation therapy . Main outcome measures : Glasgow Coma Scale , Mini-Mental State Examination , Fugl-Meyer Assessment of Motor Recovery , Clinical Neurological Deficit Scale and Modified Barthel Index ( MBI ) . Results : Patients from the AEP group had a high drop-out rate ( n = 28 ) , but those remaining made relatively better functional recovery at 30 days than those from the RT group if measured by MBI . Multiple linear regression analysis revealed that cognitive disturbance , aphasia , double incontinence , site of lesion and sensory impairment might affect functional recovery after stroke . Conclusions : Additional early physiotherapy might improve independence of patients after stroke but failed to show benefit in other aspects in our study . Cognitive disturbance , aphasia , double incontinence , site of lesion as well as sensory impairment might affect functional outcome after stroke OBJECTIVE To examine cognitive function in individuals with traumatic brain injury ( TBI ) prior to and after participation in an aerobic exercise training program . DESIGN Pre-post intervention study . SETTING Medical research center . PARTICIPANTS Volunteer sample of individuals ( N=7 ) ( age , 33.3±7.9y ) with chronic nonpenetrating TBI ( injury severity : 3=mild , 4=moderate ; time since most current injury : 4.0±5.5y ) who were ambulatory . INTERVENTION Twelve weeks of supervised vigorous aerobic exercise training performed 3 times a week for 30 minutes on a treadmill . MAIN OUTCOME MEASURES Cognitive function was assessed using the Trail Making Test Part A ( TMT-A ) , Trail Making Test Part B ( TMT-B ) , and Repeatable Battery for the Assessment of Neuropsychological Status ( RBANS ) . Sleep quality and depression were measured with the Pittsburgh Sleep Quality Index ( PSQI ) and Beck Depression Inventory , version 2 ( BDI-II ) . Indices of cardiorespiratory fitness were used to examine the relation between improvements in cognitive function and cardiorespiratory fitness . RESULTS After training , improvements in cognitive function were observed with greater scores on the TMT-A ( 10.3±6.8 ; P=.007 ) , TMT-B ( 9.6±7.0 ; P=.011 ) , and RBANS total scale ( 13.3±9.3 ; P=.009 ) . No changes were observed in measures of the PSQI and BDI-II . The magnitude of cognitive improvements was also strongly related to the gains in cardiorespiratory fitness . CONCLUSIONS These findings suggest that vigorous aerobic exercise training may improve specific aspects of cognitive function in individuals with TBI and cardiorespiratory fitness gains may be a determinant of these improvements In this issue , we answer three questions with respect to loss to follow-up in a clinical trial : How important is loss to follow-up ? How is loss to follow-up calculated ? How many patients can be lost to follow-up without mistrusting the results ? 1 . How important is loss to follow-up ? The simple answer to this question is “ very important ” because loss to follow-up can severely compromise a study 's validity . Incomplete follow-up biases the results when either : The dropout rates are different between study groups ; or The patients who drop out are different from those who do not drop out . Why do these situations make a difference ? Because in each situation , those lost to follow-up often have a different prognosis than those who complete the study . For example , patients who receive treatment for cervical myelopathy may not return for follow-up because they became asymptomatic and felt no need to return to see the surgeon . Conversely , some patients may not return because they had a particularly bad outcome ( worse pain or function ) or complication , or because they died . In either case , bias can affect the validity of the inferences drawn from the study . 2 . How is loss to follow-up calculated ? There is much confusion about how to determine the proportion of patients lost to follow-up . In order to correctly calculate the follow-up rate , one needs to know the denominator . In a r and omized controlled trial ( RCT ) , the denominator for each group is the number of patients who were r and omized , not the number who received the treatment . For example , suppose we have an RCT comparing two treatment groups , Group A and Group B. The investigators evaluate 178 patients and r and omize 120 ; 61 to Group A and 59 to Group B ( Fig 1 ) . Following the figure , we note that 49 patients received treatment A and 52 received treatment B. At the final follow-up 40 were analyzed in Group A and 41 in Group B. How many were considered lost to follow-up ? Many would consider the loss to follow-up rate to be 9 ( 18 % ) of 49 in treatment A and 11 ( 21 % ) of 52 in treatment B using as the denominator only those that were treated . However , the real proportion lost to follow-up must consider those who were r and omly assigned , even if they did not receive treatment . In the present example , this is calculated as 21 ( 34 % ) of 61 for treatment A and 18 ( 31 % ) of 59 for treatment B. Fig 1 Hypothetical example of patients lost to follow-up in a r and omized controlled trial . When calculating loss to follow-up in a retrospective cohort study , all individuals receiving treatment during the study period should be used as the denominator , not just those with complete data . For example , let 's say you want to compare decompression plus lumbar fusion with decompression alone in disc herniation and the data available are all patients receiving either treatment in the last 5 years ( N = 275 ) . However , the data base from which the data are obtained is incomplete and only 190 have the necessary data available . Since the investigators stated as part of the inclusion criteria that only those patients with complete data are included , they consider the follow-up to be 100 % ( 190/190 ) . This conclusion is wrong . The denominator should include all patients who underwent the surgery irrespective of completeness of data . The follow-up rate for this example is 69 % ( 190/275 ) . 3 . How many patients can be lost to follow-up without mistrusting the results ? Some have suggested that 20 % poses serious threats to validity 1 . This may be a good rule of thumb , but keep in mind that even small proportions of patients lost to follow-up can cause significant bias 2 . One way to determine if loss to follow-up can seriously affect results is to assume a worst-case scenario with the missing data and look to see if the results would change . Here is an example : Let 's assume a multicenter study enrolled 500 patients into each arm of a study comparing artificial disc replacement ( ADR ) with fusion , and the end point is adjacent segment disease ( ASD ) . The trial numbers are found in Fig 2 . Fig 2 Hypothetical example of the effect of loss to follow-up considering a worst-case scenario . ADR indicates artificial disc replacement ; ASD , adjacent segment disease . The proportion of patients with ASD in the ADR group is half as much versus the fusion group , 25 % ( 100/400 ) compared with 50 % ( 200/400 ) . If we assume that the 100 lost to follow-up in the ADR group had ASD and the 100 lost to follow-up in the fusion group did not , then the rate of ASD in each group would be 40 % ( 200/500 ) . In this case , adopting the worst-case scenario for the intervention group with respect to those lost to follow-up causes the results to change significantly from half the rate of ASD with ADR to the same rate . When this happens , loss to follow-up can threaten the internal validity of the trial . Only when the worst case does not change the inferences derived from the results is lost to follow-up not a problem Background and Purpose — The ability of therapeutic exercise after stroke to improve daily functioning and quality of life ( QOL ) remains controversial . We examined treatment effects on these outcomes in a r and omized controlled trial ( RCT ) of exercise in subacute stroke survivors . Methods — This is a secondary analysis of a single-blind RCT of a 12-week program versus usual care . Baseline , post-treatment and 6-month post-treatment daily functioning and QOL were assessed by Barthel index , Functional Independence Measure , instrumental activities of daily living , Medical Outcomes Study short-form 36-item question naire ( SF-36 ) , and Stroke Impact Scale ( SIS ) . Results — Of 100 r and omized subjects , 93 completed the postintervention assessment , ( mean age 70 ; 54 % male ; 81 % white ; mean Orpington Prognostic Score 3.4 ) , and 80 had 6-month post-treatment assessment . Immediately after intervention , the intervention group improved more than usual care in SF-36 social function ( 14.0 points ; P=0.0051 ) and in SIS ( strength [ 9.2 points ; P=0.0003 ] , emotion [ 5.6 points ; P=0.0240 ] , social participation [ 6.6 points ; P=0.0488 ] , and physical function [ 5.0 points ; P=0.0145 ] ) . Treatment was marginally more effective on Barthel score ( 3.3 points ; P=0.0510 ) , SF-36 ( physical function [ 6.8 points ; P=0.0586 ] , physical role function [ 14.4 points ; P=0.0708 ] ) , and SIS upper extremity function ( 7.2 points ; P=0.0790 ) . Effects were diluted 6 months after treatment ended . Conclusion — This rehabilitation exercise program led to more rapid improvement in aspects of physical , social , and role function than usual care in persons with subacute stroke . Adherence interventions to promote continued exercise after treatment might be needed to continue benefit BACKGROUND AND PURPOSE Systematic review s and meta-analyses often include an evaluation of the method ological quality of the individual studies that have been included , and are usually conducted by at least 2 individuals . The objective of this study was to assess the method ological quality and reliability of a series of r and omized controlled trials ( RCTs ) of both pharmacological and nonpharmacological interventions by use of the 10-item Physiotherapy Evidence -Based Data base ( PEDro ) Scale . METHODS Two abstract ors independently review ed 81 RCTs assessing a variety of interventions . The Cohen kappa statistic and the intraclass correlation coefficient ( ICC ) were used to assess agreement between abstract ors . RESULTS The average total PEDro scores were 5.94 ( SD=1.43 ) for all studies combined , 6.88 ( SD=1.2 ) for pharmacological studies , and 5.29 ( SD=1.26 ) for nonpharmacological studies . The median score for pharmacological studies was significantly higher than that for nonpharmacological studies ( 7 versus 5 ) . Pair-wise kappa scores ranged from a low of .452 for concealed allocation among drug trials to perfect agreement ( 1.00 ) for r and omization and reporting of results from between-group comparisons . The ICCs associated with the cumulative PEDro score were .91 ( 95 % confidence interval [CI]=.83-.94 ) for all studies , .89 ( 95 % CI=.78-.95 ) for pharmacological studies , and .91 ( 95 % CI=.84-.952 ) for nonpharmacological studies . DISCUSSION AND CONCLUSION The method ological quality for pharmacological interventions was significantly higher than that for nonpharmacological interventions . There was good agreement between raters at an individual item level and in total PEDro scores . A lack of reporting clarity , poor organization of the report , or the failure to include salient details contributed to less-than-perfect agreement between raters While the Mini-Mental State Examination ( MMSE ) was originally developed to screen for dementia and delirium , many neurologists use this measure as a screening instrument for ' cognitive impairment ' in hospitalized stroke patients . However , the validity of the MMSE as such has never been evaluated in acute stroke . We administered the MMSE in addition to a neuropsychological examination covering six cognitive domains to 34 stroke patients ( mean interval between stroke and examination , 6.5+/-2.9 days ) and 34 healthy controls . The area under the receiver operating characteristic curve ( AUC ) was calculated in addition to the sensitivity and specificity for various cut-off points on the MMSE . Seventy percent of the patients were impaired in at least one cognitive domain . The accuracy of the MMSE in detecting cognitive impairment was no better than chance ( AUC = 0.67 ; p = 0.13 ) . No optimum MMSE cut-off value could be identified . The MMSE is particularly insensitive to impairments in abstract reasoning , executive functioning , and visual perception/construction OBJECTIVE To examine the impact of fitness training with recently brain-injured in patients on exercise capacity and functional and psychologic outcome measures . DESIGN A r and omized controlled trial of exercise versus relaxation training for 3 months . Blind assessment s were conducted before and after the end of a 12-week training program , as well as at follow-up assessment 12 weeks posttraining . SETTING Four regional neurologic \n Output:\n " }, { "from": "agent", "value": "Though well- design ed studies are still needed , the preponderance of evidence suggests a positive effect of physical exercise on global cognitive functioning , especially in the chronic stages of a brain injury .\nTime after injury as well as the duration of the exercise program are mediating factors" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: BACKGROUND A need exists for a therapy that lowers parathyroid hormone ( PTH ) without increasing calcium x phosphorus in patients with secondary hyperparathyroidism . The calcimimetic AMG 073 increases the sensitivity of the parathyroid calcium-sensing receptor to extracellular calcium , thereby reducing PTH secretion . Consequently , AMG 073 may provide a novel therapy for secondary hyperparathyroidism . METHODS Seventy-eight hemodialysis patients with secondary hyperparathyroidism were enrolled into this 18-week , double-blind , r and omized , placebo-controlled , dose titration study . Daily oral AMG 073 doses were administered to determine the effect on PTH , serum calcium , phosphorus , and calcium x phosphorus . RESULTS The mean baseline PTH was similar in patients administered AMG 073 or placebo ( 632 + /- 280.1 pg/mL vs. 637 + /- 455.9 pg/mL , respectively ) . PTH decreased by 26.0 % in the AMG 073-treated group , compared with an increase of 22.0 % in the placebo group ( P < 0.001 ) . A greater proportion in the AMG 073 group ( 38 % ) had a decrease in PTH > or=30 % , compared with the placebo group ( 8 % ) ( P = 0.001 ) . Decreases in PTH were independent of baseline vitamin D usage . Patients receiving AMG 073 had an 11.9 % decrease in calcium x phosphorus compared with a 10.9 % increase in the placebo group ( P < 0.001 ) . Use of vitamin D sterols , as well as both calcium and noncalcium-containing phosphate binders . were similar between treatment groups . Administration of AMG 073 was safe and well tolerated in this 18-week study . CONCLUSIONS The calcimimetic AMG 073 decreases both PTH and calcium x phosphorus levels in hemodialysis patients with secondary hyperparathyroidism Management of secondary hyperparathyroidism is challenging with traditional therapy . The calcimimetic cinacalcet HCl acts on the calcium-sensing receptor to increase its sensitivity to calcium , thereby reducing parathyroid hormone ( PTH ) secretion . This phase 3 , multicenter , r and omized , placebo-controlled , double-blind study evaluated the efficacy and safety of cinacalcet in hemodialysis ( HD ) and peritoneal dialysis ( PD ) patients with PTH > or = 300 pg/ml despite traditional therapy . A total of 395 patients received once-daily oral cinacalcet ( 260 HD , 34 PD ) or placebo ( 89 HD , 12 PD ) titrated from 30 to 180 mg to achieve a target intact PTH ( iPTH ) level of < or = 250 pg/ml . During a 10-wk efficacy assessment phase , cinacalcet was more effective than control for PTH reduction outcomes , including proportion of patients with mean iPTH levels < or = 300 pg/ml ( 46 versus 9 % ) , proportion of patients with > or = 30 % reduction in iPTH from baseline ( 65 versus 13 % ) , and proportion of patients with > or = 20 , > or = 40 , or > or = 50 % reduction from baseline . Cinacalcet had comparable efficacy in HD and PD patients ; 50 % of PD patients achieved a mean iPTH < or = 300 pg/ml . Cinacalcet also significantly reduced serum calcium , phosphorus , and Ca x P levels compared with control treatment . The most common side effects , nausea and vomiting , were usually mild to moderate in severity and transient . Once-daily oral cinacalcet was effective in rapidly and safely reducing PTH , Ca x P , calcium , and phosphorus levels in patients who received HD or PD . Cinacalcet offers a new therapeutic option for controlling secondary hyperparathyroidism in patients with chronic kidney disease on dialysis BACKGROUND The calcimimetic agent R-568 lowers plasma parathyroid hormone ( PTH ) levels in hemodialysis patients with mild secondary hyperparathyroidism , but its efficacy in those with more severe secondary hyperparathyroidism has not been studied . METHODS Twenty-one patients undergoing hemodialysis three times per week with plasma PTH levels between 300 and 1200 pg/mL were r and omly assigned to 15 days of treatment with either 100 mg of R-568 ( N = 16 ) or placebo ( N = 5 ) . Plasma PTH and blood ionized calcium levels were measured at intervals of up to 24 hours after oral doses on days 1 , 2 , 3 , 5 , 8 , 11 , 12 , and 15 . RESULTS Pretreatment PTH levels were 599 + /- 105 ( mean + /- SE ) and 600 + /- 90 pg/mL in subjects given R-568 or placebo , respectively , and values on the first day of treatment did not change in those given placebo . In contrast , PTH levels fell by 66 + /- 5 % , 78 + /- 3 % , and 70 + /- 3 % at one , two , and four hours , respectively , after initial doses of R-568 , remaining below pretreatment values for 24 hours . Blood ionized calcium levels also decreased after the first dose of R-568 but did not change in patients given placebo . Despite lower ionized calcium concentrations on both the second and third days of treatment , predose PTH levels were 422 + /- 70 and 443 + /- 105 pg/mL , respectively , in patients given R-568 , and values fell each day by more than 50 % two hours after drug administration . Predose PTH levels declined progressively over the first nine days of treatment with R-568 and remained below pretreatment levels for the duration of study . Serum total and blood ionized calcium concentrations decreased from pretreatment levels in patients given R-568 , whereas values were unchanged in those given placebo . Blood ionized calcium levels fell below 1.0 mmol/L in 7 of 16 patients receiving R-568 ; five patients withdrew from study after developing symptoms of hypocalcemia , whereas three completed treatment after the dose of R-568 was reduced . CONCLUSIONS The calcimimetic R-568 rapidly and markedly lowers plasma PTH levels in patients with secondary hyperparathyroidism caused by end-stage renal disease BACKGROUND AND OBJECTIVES Patients with chronic kidney disease ( CKD ) receiving dialysis often develop secondary hyperparathyroidism with disturbed calcium and phosphorus metabolism . The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative ( KDOQI ) was established to guide treatment practice s for these disorders . The ACHIEVE study was design ed to test two treatment strategies for achieving KDOQI goals . DESIGN , SETTING , PARTICIPANTS , MEASUREMENTS Individuals on hemodialysis treated with vitamin D sterols were enrolled in this 33-week study . Subjects were r and omly assigned to treatment with either cinacalcet and low-dose vitamin D ( Cinacalcet-D ) or flexible vitamin D alone ( Flex-D ) to achieve KDOQI-recommended bone mineral targets . ACHIEVE included a 6-week screening phase , including vitamin D washout , a 16-week dose-titration phase , and an 11-week assessment phase . RESULTS Of 173 subjects enrolled , 83 % of Cinacalcet-D and 67 % of Flex-D subjects completed the study . A greater proportion of Cinacalcet-D versus Flex-D subjects had a > 30 % reduction in parathyroid hormone ( PTH ) ( 68 % versus 36 % , P < 0.001 ) as well as PTH < 300 pg/ml ( 44 % versus 23 % , P = 0.006 ) . The proportion of subjects simultaneously achieving targets for intact PTH ( 150 - 300 pg/ml ) and calcium-phosphorus product ( Ca x P ) ( < 55 mg2/dl2 ) was also greater ( 21 % versus 14 % ) , but this was not statistically significant . This was attributable to 19 % of Cinacalcet-D subjects with a PTH value below the KDOQI target range . CONCLUSIONS Achievement of KDOQI targets was difficult , especially with Flex-D. Maintaining calcium and phosphorus target values precluded the use of vitamin D doses necessary to lower PTH to within the narrow target range and highlighted limitations inherent to the KDOQI treatment algorithm Hyperphosphatemia is highly prevalent among patients with end-stage renal disease ( ESRD ) and is associated with increased mortality risk in hemodialysis ( HD ) patients . The mechanism through which this mortality risk is mediated is unclear . Data from two national r and om sample s of HD patients ( n = 12,833 ) was used to test the hypothesis that elevated serum PO(4 ) contributes mainly to cardiac causes of death . During a 2-yr follow-up , the cause-specific relative risk ( RR ) of death for patients was analyzed separately for several categories of cause of death , including coronary artery disease ( CAD ) , sudden death , and other cardiac causes , cerebrovascular and infection . Cox regression models were fit for each of the eight cause of death categories , adjusting for patient demographics and non-cardiovascular comorbid conditions . Time at risk for each cause-specific model was censored at death that result ed from any of the other causes . Higher mortality risk was seen for patients in the high PO(4 ) group ( > 6.5mg/dl ) compared with the lower PO(4 ) group ( < or = 6.5mg/dl ) for death result ing from CAD ( RR 1.41 ; P < 0.0005 ) , sudden death ( RR 1.20 ; P < 0.01 ) , infection ( RR 1.20 ; P < 0.05 ) , and unknown causes ( RR 1.25 ; P < 0.05 ) . Patients in the high PO(4 ) group also had non-significantly increased RR of death from other cardiac and cerebrovascular causes of death . The RR of sudden death was also strongly associated with elevated Ca x PO(4 ) product ( RR 1.07 per 10 mg(2)/dl(2 ) ; P < 0.005 ) and serum parathyroid hormone levels greater than 495 pg/ml ( RR 1.25 ; P < 0.05 ) . This study identifies strong relationships between elevated serum PO(4 ) , Ca x PO(4 ) product , and parathyroid hormone and cardiac causes of death in HD patients , especially deaths result ing from CAD and sudden death . More vigorous measures to reduce the prevalence of these factors in HD patients may result in improved survival AIMS This 1-year double-blind , placebo-controlled , multicenter study evaluated the long-term safety and efficacy of cinacalcet for the treatment of secondary hyperparathyroidism in patients receiving hemodialysis . METHOD Patients were r and omly assigned in a 1:1 ratio to cinacalcet or control treatment groups . The initial dose of cinacalcet ( or matching placebo ) was 30 mg . Doses were titrated every 3 or 4 weeks based on the intact parathyroid hormone ( iPTH ) response and safety profile . Sequential doses included 30 , 60 , 90 , 120 and 180 mg/d . Phosphate binders and vitamin D sterols were adjusted per protocol as needed to control levels of calcium and phosphorus . Efficacy and safety were compared between treatment groups among patients who completed the study ( 52 total weeks of treatment ) . Reasons for withdrawal are presented for patients who did not complete the study . RESULTS A total of 210 patients completed 52 weeks of double-blinded treatment with cinacalcet ( n = 99 ) or placebo ( n = 111 ) . Over the last 6 months of the study , a greater proportion of patients in the cinacalcet group than the control group achieved an iPTH level < or = 250 pg/ml ( 61.6 vs. 9.9 % , p < 0.001 ) or a > or = 30 % decrease in iPTH from baseline ( 81.8 vs. 21.6 % , p < 0.001 ) . Mean iPTH levels decreased by -47.8 % in the cinacalcet group and increased by + 12.9 % in the control group . Mean percentage changes in other laboratory values in the cinacalcet and control groups included the following : serum calcium -6.5 vs. + 0.9 % ( p < 0.001 ) , serum phosphorus -3.6 vs. -1.1 % ( p = 0.465 ) , and Ca x P -9.9 vs. -0.3 % ( p = 0.006 ) . The most commonly reported adverse events related to study drug by the investigators included nausea ( 13 % cinacalcet , 5 % control ) , investigator-reported hypocalcemia ( 11 % cinacalcet , 1 % control ) , vomiting ( 9 % cinacalcet , 2 % control ) , dyspepsia ( \n Output:\n " }, { "from": "agent", "value": "Calcimimetic treatment of SHPT leads to significant improvements in biochemical parameters that observational studies have shown to be associated with increased mortality , cardiovascular risk and osteitis fibrosa , but patient-based benefits have not yet been demonstrated in trials ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Differents protocol es therapeutiques et differents dosages de neuroleptiques chez des Abstract Nine VA Medical Centers are participating in a 2-year double-blind placebo controlled study of antioxidant treatment for tardive dyskinesia ( TD ) conducted by the Department of Veteran Affairs Cooperative Studies Program . One of the principal outcome measures of this study is the score derived from the instrumental assessment of upper extremity dyskinesia . Dyskinetic h and movements are quantified by assessing the variability associated with steady-state isometric force generated by the patient . In the present report , we describe the training procedures and results of a multi-center reliability assessment of this procedure . Data from nine study centers comprising 45 individual patients with six trials each ( three from left h and and three from right h and ) were reanalyzed by an independent investigator and the results were subjected to reliability assessment . For the statistic of interest ( average coefficient of variation over trials 2 and 3 for each h and , then take the larger of these two values ) , we found very high intraclass correlation coefficients for reliability over all patients across sites ( ICC = 0.995 ) . We also calculated the reliability of the measures across trials within patient for each combination of h and ( right , left , dominant ) , rater group ( site , control ) , and trials set ( all three , trials 2 and 3 ) . For a given h and and trial set , the reliability of the site raters was similar to that of the control . This study demonstrates that instrumental measures for the assessment of dyskinesia are reliable and can be implemented in multi-center studies with minimal training BACKGROUND Several open trials and case studies have reported beneficial effects following the addition of risperidone for partial responders to clozapine . The purpose of this study was to carry out a placebo-controlled , r and omized , double-blind trial of the efficacy , safety , and tolerability of adjunctive treatment with risperidone in patients with schizophrenia partially responsive to clozapine . METHOD In this 6-week double-blind study , 30 patients with DSM-IV schizophrenia who had partial response to clozapine despite being treated for a mean of 32 months were r and omly assigned to risperidone ( N = 16 ) up to 6 mg/day or placebo ( N = 14 ) . Efficacy assessment s included the Positive and Negative Syndrome Scale ( PANSS ) , the Calgary Depression Scale , the Clinical Global Impressions-Severity of Illness scale , the Global Assessment of Functioning scale , and the Quality of Life Scale . A variety of safety and tolerability measures were also obtained . Data were collected between November 2001 and July 2003 . RESULTS Significant improvement was noted in both groups on a variety of measures of psychopathology , but there was significantly greater improvement in the placebo-treated patients on the primary outcome measure , the PANSS positive symptom subscale . There were no significant differences between the treatment groups regarding extrapyramidal symptoms , weight gain , vital signs , serum clozapine levels , and QTc interval . The only side effect significantly more severe in risperidone-treated compared to placebo-treated patients was sedation . The patients treated with risperidone developed significant increases in plasma prolactin levels . CONCLUSION Adjunctive risperidone treatment in schizophrenia patients partially responsive to clozapine does not significantly improve psychopathology or quality of life compared to placebo in a 6-week period BACKGROUND Amisulpride is a substituted benzamide with high selectivity for dopamine D2 and D3 receptors . The purpose of the study was to evaluate the effect of 100 mg amisulpride in patients with predominantly negative symptoms of schizophrenia . METHOD This was a multi-centre , r and omised , parallel-group , double-blind study . Patients received either amisulpride ( 100 mg/day ) or placebo over a six-month treatment period . RESULTS A total of 141 patients were included , 69 received amisulpride , 72 placebo . Fifty-eight patients ( 41 % ) had received neuroleptic treatment prior to inclusion . The percentage of amisulpride patients completing the study ( 55 % ) was significantly higher than that with placebo ( 32 % ) , and drop-out rates due to lack of efficacy were 27 % with amisulpride and 47 % with placebo . All efficacy assessment s were statistically in favour of amisulpride compared with placebo . The overall incidence of extrapyramidal symptoms was comparable in both groups ; only five patients started anti-Parkinsonian treatment during the study ( one in the placebo and four in the amisulpride group ) . CONCLUSION Amisulpride is effective in the medium-term treatment schizophrenic patients with predominantly negative symptoms OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered \" mildly ill \" according to the CGI approximately corresponded to a PANSS total score of 58 , \" moderately ill \" to a PANSS of 75 , \" markedly ill \" to a PANSS of 95 and severely ill to a PANSS of 116 . To be \" minimally improved \" according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating \" much improved \" were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate BACKGROUND A relative lack of extrapyramidal symptoms ( EPS , i.e. , the syndromes of dystonia , parkinsonism , akathisia , dyskinesia ) is one criterion used to determine whether an antipsychotic is \" atypical . \" The extrapyramidal symptom profiles of the novel antipsychotic olanzapine and the conventional antipsychotic haloperidol were compared in a population of 2606 patients from three well-controlled prospect i ve clinical trials . METHOD Extrapyramidal symptom data were analyzed for 1796 patients treated with olanzapine ( 5 to 20 mg/day ) and 810 patients treated with haloperidol ( 5 to 20 mg/day ) for up to 6 weeks of therapy . Patients were monitored weekly by three methods of extrapyramidal symptom assessment : ( 1 ) detection of extrapyramidal adverse events ( signs and symptoms ) by casual observation , nonprobing inquiry , and spontaneous report ; ( 2 ) objective rating scale scores : and ( 3 ) use of concomitant anticholinergic medications . Emergence of EPS was assessed by ( 1 ) analysis of the incidence of extrapyramidal syndrome categories based on adverse events , ( 2 ) the incidence of extrapyramidal syndromes based on categorical analysis of rating scale scores , ( 3 ) analysis of mean maximum change in rating scale scores , and ( 4 ) categorical analysis of anticholinergic medication use . Outcome of EPS was assessed by ( 1 ) analysis of mean change in rating scale scores at endpoint and ( 2 ) mean anticholinergic use at endpoint . RESULTS Olanzapine was statistically significantly ( p = .014 , p < .001 ) superior to haloperidol in all four analyses related to emergence of EPS and in the two analyses related to outcome . Furthermore , during acute treatment , statistically significantly fewer patients treated with olanzapine ( 0.3 % ) discontinued the study because of any extrapyramidal adverse event than patients treated with haloperidol ( 2.7 % , p < .001 ) . CONCLUSION Olanzapine exhibited a statistically significantly lower extrapyramidal symptom profile than the conventional antipsychotic haloperidol at comparably effective antipsychotic doses . The lower extrapyramidal symptom profile with olanzapine was evident despite statistically significantly more frequent use of anticholinergic drugs among haloperidol-treated patients . Fewer olanzapine-treated than haloperidol-treated patients discontinued because of EPS , suggesting that olanzapine should contribute to better compliance with longer term maintenance treatment , with minimal anticholinergic-associated events Olanzapine and risperidone , both second-generation antipsychotic agents , represent two different pharmacologic strategies . Although they share some in vitro properties , they differ by virtue of their chemical structure , spectrum of receptor binding affinities , animal neuropharmacology , pharmacokinetics , and in vivo neuroimaging profile . Based on such differences , it was hypothesized that the two compounds would show distinct safety and /or efficacy characteristics . To test this hypothesis , an international , multicenter , double-blind , parallel-group , 28-week prospect i ve study was conducted with 339 patients who met DSM-IV criteria for schizophrenia , schizophreniform disorder , or schizoaffective disorder . Results of the study indicated that both olanzapine and risperidone were safe and effective in the management of psychotic symptoms . However , olanzapine demonstrated significantly greater efficacy in negative symptoms ( Scale for Assessment of Negative Symptoms summary score ) , as well as overall response rate ( > or = 40 % decrease in the Positive and Negative Syndrome Scale total score ) . Furthermore , a statistically significantly greater proportion of the olanzapine-treated than risperidone-treated patients maintained their response at 28 weeks based on Kaplan-Meier survival curves . The incidence of extrapyramidal side effects , hyperprolactinemia , and sexual dysfunction was statistically significantly lower in olanzapine-treated than risperidone-treated patients . In addition , statistically significantly fewer adverse events were reported by olanzapine-treated patients than by their risperidone-treated counterparts . Thus , the differential pre clinical profiles of these two drugs were also evident in a controlled , clinical investigation . Olanzapine seemed to have a risk-versus-benefit advantage OBJECTIVE This study was design ed to compare the efficacy and safety of five different doses of risperidone with a fixed dose of haloperidol in patients with chronic schizophrenia . METHOD After a 1-week single-blind , placebo washout phase , 99 chronic schizophrenic patients were r and omly assigned to double-blind treatment with 1 , 4 , 8 , 12 or 16 mg risperidone or 10 mg haloperidol daily for 8 weeks . Efficacy was assessed throughout the study by the Positive and Negative Syndrome Scale ( PANSS ) for schizophrenia , and Clinical Global Impression ( CGI ) . Safety assessment s included the Extrapyramidal Symptom Ratinf Scale ( ESRS ) UKU Side Effect Rating Scale , vital signs , body weight , ECG and laboratory screening . RESULTS Risperidone had a bell-shaped dose-response curve , with optimal therapeutic responses occurring at a daily dose of 8 mg . The therapeutic response to haloperidol was similar to that seen with risperidone 16 mg . Risperidone was associated with significantly less extrapyramidal symptoms than haloperidol , as assessed by the ESRS . The effect was mirrored by the requirement for antiparkinson rescue medication . Furthermore , the overall incidence of adverse events was markedly lower with the optimum dose of risperidone than with haloperidol . CONCLUSIONS Risperidone is at least as effective as haloperidol for the treatment of chronic schizophrenia . Moreover , risperidone is associated with an improved adverse event profile and significantly less extrapyramidal symptoms which will have beneficial implication s on patient quality of life and compliance . These results are in agreement with the results from the international multicenter trial OBJECTIVE The authors assessed the efficacy and safety of the first long-acting atypical antipsychotic ( long-acting injectable risperidone ) in patients with schizophrenia . METHOD In a 12-week , multicenter , double-blind , r and omized study , patients received intramuscular injections every 2 weeks of placebo or long-acting risperidone ( 25 mg , 50 mg , or 75 mg ) . The primary measure of efficacy was the change in total score on the Positive and Negative Syndrome Scale . RESULTS Of the 554 patients who were enrolled , 400 entered the double-blind study , and 370 received at least one postbaseline assessment . Mean changes in score of -6.2 , -8.5 , and -7.4 on the Positive and Negative Syndrome Scale were seen at endpoint for the 25- , 50- , and 75-mg risperidone groups \n Output:\n " }, { "from": "agent", "value": "AUTHORS ' CONCLUSIONS Based on low quality evidence , risperidone appears to be benefitial in improving mental state compared with placebo , but it also causes more adverse events ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: OBJECTIVE Computerized medical decision support tools have been shown to improve the quality of care and have been cited by the Institute of Medicine as one method to reduce pharmaceutical errors . We evaluated the impact of an antiinfective decision support tool in a pediatric intensive care unit ( PICU ) . METHODS We enhanced an existing adult antiinfective management tool by adding and changing medical logic to make it appropriate for pediatric patients . Process and outcomes measures were monitored prospect ively during a 6-month control and a 6-month intervention period . M and atory use of the decision support tool was initiated for all antiinfective orders in a 26-bed PICU during the intervention period . Clinician opinions of the decision support tool were surveyed via question naire . RESULTS The rate of pharmacy interventions for erroneous drug doses declined by 59 % . The rate of anti-infective subtherapeutic patient days decreased by 36 % , and the rate of excessive-dose days declined by 28 % . The number of orders placed per antiinfective course decreased 11.5 % , and the robust estimate of the antiinfective costs per patient decreased 9 % . The type of anti-infectives ordered and the number of antiinfective doses per patient remained similar , as did the rates of adverse drug events and antibiotic-bacterial susceptibility mismatches . The surveyed clinicians reported that use of the program improved their antiinfective agent choices as well as their awareness of impairments in renal function and reduced the likelihood of adverse drug events . CONCLUSIONS Use of the pediatric antiinfective decision support tool in a PICU was considered beneficial to patient care by the clinicians and reduced the rates of erroneous drug orders , improved therapeutic dosage targets , and was associated with a decreased robust estimate of antiinfective costs per patient . antiinfective agents , decision support systems , drug therapy , medication errors , child , infant BACKGROUND Adverse drug-related events are common in the elderly , and inappropriate prescribing is a preventable risk factor . Our objective was to determine whether inappropriate prescribing could be reduced when primary care physicians had computer-based access to information on all prescriptions dispensed and automated alerts for potential prescribing problems . METHODS We r and omly assigned 107 primary care physicians with at least 100 patients aged 66 years and older ( total 12 560 ) to a group receiving computerized decision-making support ( CDS ) or a control group . Physicians in the CDS group had access to information on current and past prescriptions through a dedicated computer link to the provincial seniors ' drug-insurance program . When any of 159 clinical ly relevant prescribing problems were identified by the CDS software , the physician received an alert that identified the nature of the problem , possible consequences and alternative therapy . The rate of initiation and discontinuation of potentially inappropriate prescriptions was assessed over a 13-month period . RESULTS In the 2 months before the study , 31.8 % of the patients in the CDS group and 33.3 % of those in the control group had at least 1 potentially inappropriate prescription . During the study the number of new potentially inappropriate prescriptions per 1000 visits was significantly lower ( 18 % ) in the CDS group than in the control group ( relative rate [ RR ] 0.82 , 95 % confidence interval [ CI ] 0.69 - 0.98 ) , but differences between the groups in the rate of discontinuation of potentially inappropriate prescriptions were significant only for therapeutic duplication by the study physician and another physician ( RR 1.66 , 95 % CI 0.99 - 2.79 ) and drug interactions caused by prescriptions written by the study physician ( RR 2.15 , 95 % CI 0.98 - 4.70 ) . INTERPRETATION Computer-based access to complete drug profiles and alerts about potential prescribing problems reduces the rate of initiation of potentially inappropriate prescriptions but has a more selective effect on the discontinuation of such prescriptions BACKGROUND Medication errors are common , and while most such errors have little potential for harm they cause substantial extra work in hospitals . A small proportion do have the potential to cause injury , and some cause preventable adverse drug events . OBJECTIVE To evaluate the impact of computerized physician order entry ( POE ) with decision support in reducing the number of medication errors . DESIGN Prospect i ve time series analysis , with four periods . SETTING AND PARTICIPANTS All patients admitted to three medical units were studied for seven to ten-week periods in four different years . The baseline period was before implementation of POE , and the remaining three were after . Sophistication of POE increased with each successive period . INTERVENTION Physician order entry with decision support features such as drug allergy and drug-drug interaction warnings . MAIN OUTCOME MEASURE Medication errors , excluding missed dose errors . RESULTS During the study , the non-missed-dose medication error rate fell 81 percent , from 142 per 1,000 patient-days in the baseline period to 26.6 per 1,000 patient-days in the final period ( P < 0.0001 ) . Non-intercepted serious medication errors ( those with the potential to cause injury ) fell 86 percent from baseline to period 3 , the final period ( P = 0.0003 ) . Large differences were seen for all main types of medication errors : dose errors , frequency errors , route errors , substitution errors , and allergies . For example , in the baseline period there were ten allergy errors , but only two in the following three periods combined ( P < 0.0001 ) . CONCLUSIONS Computerized POE substantially decreased the rate of non-missed-dose medication errors . A major reduction in errors was achieved with the initial version of the system , and further reductions were found with addition of decision support features BACKGROUND Physicians frequently need to start antibiotic therapy before the results of bacterial cultures and antibiotic susceptibility tests are available . We developed and evaluated a computerized antibiotic consultant to assist physicians in the selection of appropriate empiric antibiotics . METHODS We used a two-stage r and om- selection study to compare antibiotics suggested by the antibiotic consultant with 482 associated antibiotic susceptibility results and the concurrent antibiotics ordered by physicians . The antibiotics ordered by r and omized physicians were then compared between crossover periods of antibiotic consultant use . RESULTS The antibiotic consultant suggested an antibiotic regimen to which all isolated pathogens were shown to be susceptible for 453 ( 94 % ) of 482 culture results , while physicians ordered an antibiotic regimen to which all isolated pathogens were susceptible for 369 culture results ( 77 % ) ( P < .001 ) . The physicians who prescribed antibiotics to which all pathogens were susceptible did so a mean of 21 hours after the culture specimens were collected . Physicians ordered appropriate antibiotics within 12 hours of the culture collection significantly more often when they had use of the antibiotic consultant than during the period before use ( P < .035 ) . Moreover , 88 % of the physicians stated they would recommend the program to other physicians , 85 % said the program improved their antibiotic selection , and 81 % said they felt use of the program improved patient care . CONCLUSIONS Information from computer-based medical records can be used to help improve physicians ' selection of empiric antibiotics for infections Introduction Medication errors in the intensive care unit ( ICU ) are frequent and lead to attributable patient morbidity and mortality , increased length of ICU stay and substantial extra costs . We investigated if the introduction of a computerized ICU system ( Centricity Critical Care Clinisoft , GE Healthcare ) reduced the incidence and severity of medication prescription errors ( MPEs ) . Methods A prospect i ve trial was conducted in a paper-based unit ( PB-U ) versus a computerized unit ( C-U ) in a 22-bed ICU of a tertiary university hospital . Every medication order and medication prescription error was vali date d by a clinical pharmacist . The registration of different classes of MPE was done according to the National Coordinating Council for Medication Error Reporting and Prevention guidelines . An independent panel evaluated the severity of MPEs . We identified three groups : minor MPEs ( no potential to cause harm ) ; intercepted MPEs ( potential to cause harm but intercepted on time ) ; and serious MPEs ( non-intercepted potential adverse drug events ( ADE ) or ADEs , being MPEs with potential to cause , or actually causing , patient harm ) . Results The C-U and the PB-U each contained 80 patient-days , and a total of 2,510 medication prescriptions were evaluated . The clinical pharmacist identified 375 MPEs . The incidence of MPEs was significantly lower in the C-U compared with the PB-U ( 44/1286 ( 3.4 % ) versus 331/1224 ( 27.0 % ) ; P < 0.001 ) . There were significantly less minor MPEs in the C-U than in the PB-U ( 9 versus 225 ; P < 0.001 ) . Intercepted MPEs were also lower in the C-U ( 12 versus 46 ; P < 0.001 ) , as well as the non-intercepted potential ADEs ( 21 versus 48 ; P < 0.001 ) . There was also a reduction of ADEs ( 2 in the C-U versus 12 in the PB-U ; P < 0.01 ) . No fatal errors occurred . The most frequent drug classes involved were cardiovascular medication and antibiotics in both groups . Patients with renal failure experienced less dosing errors in the C-U versus the PB-U ( 12 versus 35 serious MPEs ; P < 0.001 ) . Conclusion The ICU computerization , including the medication order entry , result ed in a significant decrease in the occurrence and severity of medication errors in the ICU Introduction The study aim ed to compare the impact of computerised physician order entry ( CPOE ) without decision support with h and -written prescribing ( HWP ) on the frequency , type and outcome of medication errors ( MEs ) in the intensive care unit . Methods Details of MEs were collected before , and at several time points after , the change from HWP to CPOE . The study was conducted in a London teaching hospital 's 22-bedded general ICU . The sampling periods were 28 weeks before and 2 , 10 , 25 and 37 weeks after introduction of CPOE . The unit pharmacist prospect ively recorded details of MEs and the total number of drugs prescribed daily during the data collection periods , during the course of his normal chart review . Results The total proportion of MEs was significantly lower with CPOE ( 117 errors from 2429 prescriptions , 4.8 % ) than with HWP ( 69 errors from 1036 prescriptions , 6.7 % ) ( p < 0.04 ) . The proportion of errors reduced with time following the introduction of CPOE ( p < 0.001 ) . Two errors with CPOE led to patient harm requiring an increase in length of stay and , if administered , three prescriptions with CPOE could potentially have led to permanent harm or death . Differences in the types of error between systems were noted . There was a reduction in major/moderate patient outcomes with CPOE when non-intercepted and intercepted errors were combined ( p = 0.01 ) . The mean baseline APACHE II score did not differ significantly between the HWP and the CPOE periods ( 19.4 versus 20.0 , respectively , p = 0.71 ) . Conclusion Introduction of CPOE was associated with a reduction in the proportion of MEs and an improvement in the overall patient outcome score ( if intercepted errors were included ) . Moderate and major errors , however , remain a significant concern with CPOE CONTEXT Adverse drug events ( ADEs ) are a significant and costly cause of injury during hospitalization . OBJECTIVES To evaluate the efficacy of 2 interventions for preventing nonintercepted serious medication errors , defined as those that either result ed in or had potential to result in an ADE and were not intercepted before reaching the patient . DESIGN Before-after comparison between phase 1 ( baseline ) and phase 2 ( after intervention was implemented ) and , within phase 2 , a r and omized comparison between physician computer order entry ( POE ) and the combination of POE plus a team intervention . SETTING Large tertiary care hospital . PARTICIPANTS For the comparison of phase 1 and 2 , all patients admitted to a stratified r and om sample of 6 medical and surgical units in a tertiary care hospital over a 6-month period , and for the r and omized comparison during phase 2 , all patients admitted to the same units and 2 r and omly selected additional units over a subsequent 9-month period . INTERVENTIONS A physician computer order entry system ( POE ) for all units and a team-based intervention that included changing the role of pharmacists , implemented for half the units . MAIN OUTCOME MEASURE Nonintercepted serious medication errors . RESULTS Comparing identical units between phases 1 and 2 , nonintercepted serious medication errors decreased 55 % , from 10.7 events per 1000 patient-days to 4.86 events per 1000 ( P=.01 ) . The decline occurred for all stages of the medication-use process . Preventable ADEs declined 17 % from 4.69 to 3.88 ( P=.37 ) , while nonintercepted potential ADEs declined 84 % from 5.99 to 0.98 per 1000 patient-days ( P=.002 ) . When POE-only was compared with the POE plus team intervention combined , the team intervention conferred no additional benefit over PO \n Output:\n " }, { "from": "agent", "value": "Concluding , it seems that electronic prescribing can reduce the risk for medication errors and ADE ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Background : The effect of regular and expected printed educational material s on physician prescribing behaviour has not been studied . We sought to measure the impact of a series of evidence -based drug therapy letters mailed to physicians in British Columbia on prescribing to newly treated patients . Methods : A paired , cluster r and omized community design was used . The study population included 499 physicians from 24 local health areas in British Columbia . Local health areas were paired by number of physicians , and 1 of each pair was r and omly selected and its physicians assigned to an intervention group or a control group . The intervention was 12 issues of an evidence -based series called Therapeutics Letter . Physicians in the control group ( n = 241 ) received the letters 3–8 months after physicians in the intervention group ( n = 258 ) . The impact on prescribing to newly treated patients ( defined as patients who had not previously made a cl aim for any medication from the class of drugs profiled in the letter ) was analyzed using the drug cl aims data base of BC Pharmacare , a publicly funded drug benefits program that covered all seniors and people receiving social assistance . Results : The probability of prescribing a drug recommended in the Therapeutics Letter rather than another drug in the same class increased by 30 % in the 3 months after the mailing of the letter relative to the preceding 3 months , adjusted for any before – after changes in the control group ( relative risk 1.30 ; 95 % confidence interval 1.13–1.52 ) . No letter achieved statistical significance on its own . However , 11 of the 12 letters produced prescribing changes in the predicted direction such that the overall result was significant when their effect was combined . Interpretation : The combined effect of an ongoing series of printed letters distributed from a credible and trusted source can have a clinical ly significant effect on prescribing to newly treated patients This study tests whether a managed behavioral health care organization can influence adherence to practice guidelines for the treatment of major depression in a r and omized trial of guideline dissemination . Guidelines were disseminated to mental health clinicians ( N=443 ) under one of three conditions : ( 1 ) a general mailing of guidelines to clinicians , ( 2 ) a mailing in which guidelines were targeted to a patient starting treatment with the clinician , and ( 3 ) no mailing of guidelines . The results showed no effects of guideline dissemination as measured by self-report of patients and clinicians and through episode characteristics derived from cl aims data , despite sentinel effects . Results also showed high rates of clinician-reported guideline adherence that were not detected in the cl aims data , indicating significant undertreatment of depression . Results suggest that mental health systems must look to other dissemination strategies to improve adherence to st and ards of care and raise the performance of independent practicing Little is known about incorporation of new knowledge from r and omised clinical trials into clinical practice . Thrombolytic therapy was shown to reduce the mortality of acute myocardial infa rct ion in several large trials published during 1986 - 88 . To examine the effect of these data on clinical practice , we analysed the supply of thrombolytic drugs in a representative English region ( population 4.7 million ) in 1987 - 92 . During the study period there were over 10,000 hospital admissions per year in the region for acute myocardial infa rct ion . From a very low initial level , thrombolytic drug use rose slowly for several years after publication of the trial results and reached a plateau in 1991 - 92 . Rates of use per 1000 patients admitted with myocardial infa rct ion varied almost six-fold between districts in 1989 - 90 and over two-fold in 1991 - 92 . Level of use attained by districts in the latter period was strongly associated with the extent of their previous participation in multicentre trials of thrombolysis ( p = 0.003 ) ; we estimate that 35 - 50 % of patients admitted with acute myocardial infa rct ion were receiving thrombolytics . The full potential of thrombolytic treatment has still not been achieved in routine care and the limiting factors need to be defined Study Design . Back‐injured workers with high disability risk scores on a predictive question naire participated in a r and omized , controlled trial of physician notification , with outcomes follow‐up 3 months after injury . Objectives . To test whether physician intervention improves return to work and self‐ assessment outcomes for people at relatively high risk for disability . Summary of Background Data . Only a small number of back‐injured workers suffer significant disability . Ouick identification of these people would facilitate more efficient targeting and trials of interventions . Controlling variations in practice through practice guidelines has been recommended as a promising strategy for improving care and reducing disability . Methods . Workers filing back injury reports responded to a disability prediction question naire . Those with high risk scores were r and omly assigned to control or intervention groups . Patient‐ design ated physicians in the intervention group received two letters identifying the patient 's risk and making recommendations for care , including the Agency for Health Care Policy and Research 's algorithms for acute low back pain . Predictive accuracy of the question naire and efficacy of physician intervention were evaluated on the basis of work status and self‐ assessment s 3 months after injury . Results . Of the 268 workers completing the question naire portion of the study , 32 ( 12 % ) were out of work because of back pain 3 months after injury . The question naire 's predictive accuracy included maximum κ of 0.277 and a receiver operating curve area of 0.78 . Fifty‐three people completed the physician intervention trial . The intervention had no significant impact on return to work , self‐assessed pain , or satisfaction with health care . Conclusions . Stratification of back‐injured people according to disability risk can can increase intervention efficiency by identifying those who require treatment and sparing those who do not . The apparent failure of risk notification and practice guidelines to reduce disability in this study may be improved by different application methods in the future BACKGROUND Public agencies responsible for implementing health care policies often adapt and disseminate clinical practice guidelines , but the effectiveness of mass dissemination of guidelines is unknown . AIM To study the effects of guideline dissemination on physicians ' prescribing practice s for the treatment of stable angina pectoris . DESIGN R and omized controlled trial . METHODS A sample of 3293 Quebec physicians were r and omly assigned to receive a one-page summary of clinical practice guidelines on the treatment of stable angina ( in February 1999 ) , to receive the summary and a reminder ( in February and March 1999 , respectively ) , or to receive no intervention ( controls ) . The prescribing profiles of participants , as well as sociodemographic characteristics of the physicians and their patients , were examined for June-December 1999 . RESULTS The intervention had no effect on prescription rates of beta-blockers , antiplatelet agents , or hypolipaemic drugs . Compared to 1997 data for the same physicians , there was an overall 10 % increase in appropriate prescription rates , irrespective of the intervention . DISCUSSION In-house production and dissemination of clinical practice guidelines may not improve physicians ' practice patterns if there is pre-existing substantial scientific consensus on the issue Health risk appraisal ( HRA ) remains one of the most widely used health promotion tools despite only equivocal evidence for its effectiveness . Theories of behavior change predict conventional HRA 's ineffectiveness because risk information alone is seldom sufficient to change complex behaviors . In this study , a r and omized trial compared the effects of feedback from an enhanced HRA with a typical HRA and a control group among adult patients from eight family medicine practice s. The enhanced HRA assessed behavior-specific psychosocial factors and provided patients with computer-generated , individually-tailored behavior change information in addition to typical HRA risk feedback . Changes in seven behaviors were assessed at a 6 month follow-up . Overall , patients receiving enhanced HRA feedback were 18 % more likely to change at least one risk behavior than were patients receiving typical HRA feedback or no feedback ( OR = 1.18 , 95 % CI = 1.00 , 1.39 ) . The enhanced HRA feedback appeared to promote changes in cholesterol screening , dietary fat consumption and physical activity , but not in smoking , seat belt use , mammography and Pap smears . We conclude that the addition of theory-based , individually-tailored behavior change information may improve the effectiveness of HRA The cost-effectiveness of quality assurance programs is often poorly documented , especially for innovative approaches . The authors analyzed the economic effects of an experimental educational outreach program design ed to reduce inappropriate drug prescribing , based on a four-state r and omized controlled trial ( N = 435 physicians ) . Primary care physicians r and omized into the face-to-face group were offered two individualized educational sessions with clinical pharmacists , lasting an average of 18 minutes each , concerning optimal use of three drug groups that are often used inappropriately . After the program , expenditures for target drugs prescribed by these physicians to Medicaid patients decreased by 13 % , compared with controls ( P = 0.002 ) ; this effect was stable over three quarters . Implementation of this program for 10,000 physicians would lead to projected drug savings ( to Medicaid only ) of $ 2,050,000 , compared with re source costs of $ 940,000 . Net savings remain high , even after adjustment for use of substitution medications . Although there was a ninefold difference in average preintervention prescribing levels between the highest and lowest thirds of the sample , all groups reduced target drug expenditures at the same rate . Targeting of higher-volume prescribers would thus further raise the observed benefit-to-cost ratio from approximately 1.8 to at least 3.0 . Net benefits would also increase further if non-Medicaid savings were added , or if the analysis included quality -of-care considerations . Although print material s alone may be marginally cost-effective , print plus face-to-face approaches offer greater net benefits . The authors conclude that a program of brief , face-to-face “ detailing ” visits conducted by academic rather than commercial sources can be a highly cost-effective method for improving drug therapy decisions . Such an approach makes possible the enhancement of physicians ' clinical expertise without relying on restriction of drug choices In order to increase physicians ' adherence to recommended st and ards of medical care and to examine factors presumed to contribute to such changes , we conducted a r and omized , controlled trial using reading material s targeted to specific practice recommendations . Seventy-nine internal medicine residents completed baseline question naires stating their intentions to follow 13 common preventive care actions . They were r and omly assigned to receive one of two different sets of readings covering these care actions . Thus , each physician was in the experimental group for one set of readings ( A or B ) while serving as a control for the other set . The impact of the reading was determined by : the physicians ' knowledge of the recommended care actions detailed in the combined readings , their post-reading intentions , and clinical behavior when faced with patients having indications for the recommended actions . The 73 residents ( 92 % ) who read the material judged 39 % of the information to be new and 72 % useful . Residents had significantly better performance on the knowledge questions based on their own readings than did their control group peers for both sets of readings . For the Group A physicians , reading significantly ( P less than 0.05 ) increased intentions to follow one of the seven clinical actions while Group B residents increased their intentions in three out of six . Step-wise multiple regression analyses were used to predict physicians ' post-reading adherence to the recommended actions . For the Group A actions , pre-reading actions accounted for most of the variance in their post-reading actions . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Radiological tests are often used by general practitioners ( GPs ) . These tests can be overused and contribute little to clinical management . We aim ed to assess two methods of reducing GP requests for radiological tests in accordance with the UK Royal College of Radiologists ' guidelines on lumbar spine and knee radiographs . METHODS We assessed audit and feedback , and educational reminder messages in six radiology departments and 244 general practice s that they served . The study was a before- and -after , pragmatic , cluster r and omised controlled trial with a 232 factorial design . A r and om subset of GP patients ' records were examined for concordance with the guidelines . The main outcome measure was number of radiograph requests per 1000 patients per year . Analysis was by intention to treat . FINDINGS The effect of educational reminder messages ( ie , the change in request rate after intervention ) was an absolute change of -1.53 ( 95 % CI -2.5 to -0.57 ) for lumbar spine and of -1.61 ( -2.6 to -0.62 ) for knee radiographs , both relative reductions of about 20 % . The effect of audit and feedback was an absolute change of -0.07 ( -1.3 to 0.9 ) for lumbar spine of 0.04 ( -0.95 to 1.03 ) for knee radiograph requests , both relative reductions of about 1 % . Concordance between groups did not differ significantly . INTERPRETATION 6-monthly feedback of audit data is ineffective but the routine attachment of educational reminder messages to radiographs is effective and does not affect quality of referrals . Any department of radiology that h and les referrals from primary care could deliver this intervention to good effect Documentation of unexplained geographic variations in medical practice s [ 1 ] and use of interventions inappropriately [ 2 ] or before their effectiveness has been established [ 3 ] has led to the rapid proliferation of clinical practice guidelines . These systematic ally developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances [ 4 ] are an attempt to discourage ineffective medical practice s , encourage effective practice s , and improve health outcomes [ 5 - 10 ] . Despite increasing enthusiasm for guidelines , evidence \n Output:\n " }, { "from": "agent", "value": "Evidence from this review showed that PEMs appear to have small beneficial effects on professional practice .\nThe results of this review suggest that when compared to no intervention , PEMs when used alone may have a beneficial effect on process outcomes but not on patient outcomes .\nDespite this wide of range of effects reported for PEMs , clinical significance of the observed effect sizes is not known .\nThere is insufficient information about how to optimise educational material s. The effectiveness of educational material s compared to other interventions is uncertain" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: INTRODUCTION Transurethral resection syndrome is an uncommon but potentially life threatening complication . Various irrigating solutions have been used , normal saline being the most physiological . The recent availability of bipolar cautery has permitted the use of normal saline irrigation . MATERIAL AND METHODS In a r and omized prospect i ve study , we compared the safety and efficacy of bipolar cautery ( using 0.9 % normal saline irrigation ) versus conventional monopolar cautery ( using 1.5 % glycine irrigation ) . Pre and postoperative hemoglobin ( Hb ) and hematocrit values were compared . Hemodynamics and arterial oxygen saturation were monitored throughout the study . Safety end points were changes in serum electrolytes , osmolarity and Hb/PCV ( packed cell volume ) . Efficacy parameters were the International Prostate Symptom Score ( IPSS ) and Qmax ( maximum flow rate in mL/sec ) values . RESULTS Mean preoperative prostate size on ultrasound was 60 + /- 20cc . Mean resected weight was 17.6 + /- 10.8 g ( glycine ) and 18.66 + /- 12.1 g ( saline ) . Mean resection time was 56.76 + /- 14.51 min ( glycine ) and 55.1 + /- 13.3 min ( saline ) . The monopolar glycine group showed a greater decline in serum sodium and osmolarity ( 4.12 meq/L and 5.14 mosmol/L ) compared to the bipolar saline group ( 1.25 meq/L and 0.43 mosmol/L ) . However , this was not considered statistically significant . The monopolar glycine group showed a statistically significant decline in Hb and PCV ( 0.97 gm % , 2.83 , p < 0.005 ) as compared to the bipolar saline group ( 0.55 gm % and 1.62 , p < 0.05 ) . Patient follow- up ( 1,3,6 and 12 months postoperatively ) demonstrated an improvement in IPSS and Qmax in both the groups . CONCLUSION We concluded that bipolar transurethral resection of prostate is clinical ly comparable to monopolar transurethral resection of prostate with an improved safety profile . However , larger number of patients with longer follow up is essential Objectives : To compare clinical results of plasmakinetic ( PK ) resection vs. st and ard monopolar resection of the prostate , i.e. transurethral resection of the prostate ( TURP ) . Material s and Methods : 48 patients were included in this study between January 2003 and October 2003 . They were r and omized into two groups ( TURP : PK ) with a ratio of 1:1 . PK resections ( n = 24 ) were carried out by using PlasmaKinetic Tissue Management System ( Gyrus Medical Ltd , Cardiff , UK ) and PlasmaSect electrodes . TURPs ( n = 24 ) were done by using a 26-Fr continuous-flow resectoscope and Karl Storz 27040 electrodes . Patients were assessed for safety and efficacy by measuring the IPSS and maximum flow rates at 1 , 3 , 6 and 12 months and residual urine measurement at 3 , 6 and 12 months and transrectal ultrasonography at 6 months . Results : The patients ’ ages ranged from 50 to 82 ( mean 64 ± 10 ) years . Groups were similar for operation time , bleeding score , resected tissue , catheterization time and irrigated volume . Mean serum Na levels at the end of the operation were 141.7 ± 5.1 in the TURP group and 145.2 ± 4.4 in the PK group ( p = 0.013 ) . The IPSS , QOL score and Qmax had improved significantly in the postoperative period without any differences in either group . Conclusions : The main advantage of PK resection seems to be decreasing the risk of TUR syndrome , thus , larger prostates could be treated without a time limitation , theoretically . However , this technique brings no advantages in terms of intra- and postoperative bleeding , hospital stay , operation time and late complications Purpose To report the 5-year follow-up results of a r and omized controlled trial comparing bipolar transurethral resection of the prostate ( TURP ) with st and ard monopolar TURP for the treatment of benign prostatic obstruction ( BPO ) . Material s and Methods A total of 220 patients were r and omized to bipolar plasmakinetic TURP ( PK-TURP ) or monopolar TURP ( M-TURP ) . Catheterization time was the primary endpoint of this study . Secondary outcomes included operation time , hospital stay , as well as decline in postoperative serum sodium and hemoglobin levels . All patients were assessed preoperatively and followed-up at 1 , 6 , 12 , 24 , 36 , 48 , and 60 months postoperatively . Parameters assessed included quality of life , transrectal ultrasound , serum prostate-specific antigen level , postvoid residual urine volume , maximum urinary flow rates ( Qmax ) , and International Prostate Symptom Score . Patient baseline characteristics , perioperative data including complications , and postoperative outcomes were compared . Complication occurrence was grade d according to the modified Clavien classification system . Results PK-TURP was significantly superior to M-TURP in terms of operation time , intraoperative irrigation volume , resected tissue weight , decreases in hemoglobin and sodium , postoperative irrigation volume and time , catheterization time , and hospital stay . At 5 years postoperatively , efficacy was comparable between arms . No differences were detected in safety outcomes except that the clot retention rate was significantly greater after M-TURP . Conclusion Our results indicate that PK-TURP is equally as effective in the treatment of BPO , but has a more favorable safety profile in comparison to M-TURP . The clinical efficacy of PK-TURP is long-lasting and comparable with M-TURP Introduction : We compare the absorption of irrigant fluid during gyrus plasmakinetic transurethral prostatectomy ( PK-TURP ) and transurethral resection of the prostate ( TURP ) . Patients and Methods : 42 patients with clinical benign prostatic hyperplasia were r and omly assigned to undergo PK-TURP or TURP . In the PK-TURP group 0.9 % NaCl was used as an irrigation fluid and 1.5 % glycine in the TURP group . By adding ethanol to the irrigation fluids 1 % ethanol-containing solutions were formed . All operations were carried out under spinal anesthesia and alcohol concentration of the ventilated air measurements were made just at the beginning of the operation , every 10 min peroperatively and at the end of the operation by using an alcoholmeter . Results : There was no difference in age , prostate volume and the length of operation time in either group . In both groups , the estimated absorbed fluid volume increased with the duration of surgery ( p < 0.05 ) . The difference between mean fluid absorption during PK-TURP and during TURP was the statistically significant ( p < 0.01 ) . Conclusion : PK-TURP operation causes lesser absorption of the irrigation fluid than the TURP operation . The lesser absorption of irrigation fluid and using saline instead of glycine decreases the risk of TUR syndrome OBJECTIVES To compare bipolar plasmakinetic ( PK ) with st and ard monopolar transurethral resection of the prostate ( TURP ) . METHODS A total of 70 patients were prospect ively r and omized into two groups : 35 patients underwent PK TURP with the Gyrus device , and 35 patients underwent st and ard monopolar TURP . We evaluated the time to catheter removal and hospital discharge , operating time , blood loss , postoperative irrigation , complications , urinary flow rates , symptom relief , and postvoid residual volumes . RESULTS At baseline , the study groups were comparable in age , prostate volume , mean prostate-specific antigen value , International Prostate Symptom Score , quality -of-life score , flow rate , and postvoid residual volume . The mean catheterization time was 72 and 100 hours in the PK and st and ard groups , respectively . This difference was statistically significant ( P < 0.05 ) , as was the difference in the time to hospital discharge . No difference was found in the mean resection time , amount of resected tissue , or variations in hemoglobin and sodium levels . The improvement in flow rate , postvoid residual volume , International Prostate Symptom Score , and quality -of-life score was comparable between the two groups at 12 months of follow-up . CONCLUSIONS In our experience , PK TURP showed comparable perioperative results to those obtained with st and ard TURP , but with more favorable postoperative outcomes . The resection time and blood loss were similar between the two groups , but the need for continuous bladder irrigation after surgery and time to catheter removal and hospital discharge were significantly shorter in the PK group BACKGROUND AND PURPOSE Today , urologists around the world are encountering greater numbers of larger prostate gl and s , probably because of an initial trial of pharmacotherapy . The present study was performed to assess the safety and efficacy of bipolar transurethral resection of large prostate gl and s using the PlasmaKinetic ( PK ) Superpulse System . PATIENTS AND METHODS This single-blind , r and omized study included 70 patients with prostate gl and > 60 g seen on three-dimensional transrectal ultrasonography . Patients were r and omized 1:1 using envelopes into either a PK Superpulse transurethral resection of the prostate ( TURP ) group or conventional TURP group , and underwent the procedure accordingly . Perioperative and postoperative parameters included operative time , blood loss , need for blood transfusion , clinical transurethral resection ( TUR ) syndrome , and duration of catheterization and hospitalization . Of 70 patients , 67 were followed for a minimum of 9 months , and data were analyzed using SPSS software . RESULTS Both groups were comparable in terms of preoperative parameters , which included American Urological Association Symptom Score , Qmax , gl and size , and postvoid residual . A statistically significant difference between the two groups was found in terms of perioperative blood loss , change in serum sodium , and duration of catheterization . These complications were significantly less in the PK Superpulse group , with an obvious reduction in the duration of hospitalization in that group . CONCLUSION The PK Superpulse System can be used as safely and effectively in the resection of the large gl and ( > 60 g ) as it has been reported to be in the resection of small and medium-sized gl and s. By using physiologic saline ( 0.9 % NaCl ) as irrigation fluid , it eliminates any danger of TUR syndrome and thus eliminates the conventional time limit of resection . PK Superpulse TURP is a promising treatment modality in the management of large prostate gl and s. It has all the features of gold-st and ard monopolar TURP , along with added safety and efficacy . It is ready to be included in the urologist 's armamentarium Introduction : This r and omized prospect i ve study was conducted to compare the efficacy and safety of the Gyrus Plasmasect loop bipolar transurethral resection of prostate ( TURP ) and conventional monopolar TURP in the treatment of benign prostatic hyperplasia ( BPH ) . Material s and Methods : A total of 117 men were enrolled in this study . Fifty-eight patients underwent Gyrus Plasmasect TURP and 59 patients underwent monopolar TURP . They were followed up for 3 months after surgery . Results : Significant improvements were seen postoperatively in both the Gyrus and monopolar groups in terms of prostatic volume , International Prostate Symptom Score , quality of life score , peak flow rate , and post-void residual urine volume . However , the degree of improvement was not statistically different between the 2 groups . Significantly less blood loss , shorter postoperative catheterization time and length of hospital stay were seen in the Gyrus group . Conclusions : Gyrus Plasmasect TURP yielded comparable results to monopolar TURP ; however , this is only a preliminary study and follow-up is necessary to assess its long-term efficacy PURPOSE To compare the efficacy and safety of the PlasmaKinetic ( PK ) Superpulse system with that of conventional transurethral resection of the prostate ( TURP ) in terms of restoration of urinary flow and early postoperative course . PATIENTS AND METHODS One hundred five men older than 45 years with lower-urinary tract symptoms associated with benign prostatic hyperplasia ( BPH ) were r and omized , 51 undergoing st and ard TURP with glycine as the irrigation fluid and 53 TURP with the PK Superpulse system with normal saline as irrigant . The operative time , intraoperative blood loss , catheter time , change in serum electrolytes ( particularly sodium ) , and uroflowmetry and American Urological Association ( AUA ) Symptom Scores were compared . RESULTS The blood loss as well as the catheter time observed in the PK Superpulse arm were significantly less than those in the conventional-TURP arm . The mortality rate was 0 in both the arms . The mean operative time was less in the PK Superpulse arm , although not significantly so . Hyponatremia was statistically insignificant . Significant changes were observed in the AUA Scores in both arms . CONCLUSION The PK Superpulse system provides \n Output:\n " }, { "from": "agent", "value": "Meta-analyses showed that PKRP significantly improved Qmax at 12 months , but no significant difference was found for other efficacy outcomes .\nIn terms of safety , treatment of PKRP was associated with reduced drop in serum sodium , lower TUR syndrome , reduced need of blood transfusion , clot retention , and shorter catheterization time and hospital stay ; in contrast , there were no significant differences in the analysis of operative time , postoperative fever , and long-term postoperative complications .\nIn summary , current evidence suggests that , although PKRP and TURP are both effective for BPH , PKRP is associated with additional potential benefits in efficacy and more favorable safety profile ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: & NA ; ‘ Diffuse noxious inhibitory controls ’ ( DNIC ) , a form of supraspinal descending endogenous analgesia , requires a noxious conditioning stimulus for pain attenuation . This may be partly dependent on a distraction effect . The term “ conditioned pain modulation ” ( CPM ) has recently been introduced to describe the psychophysical paradigm to test DNIC . The present study aim ed to determine whether distraction and tonic heat stimulation inhibit pain through the same or different mechanisms by looking at whether there is a similar or even an additive effect on pain attenuation . Test pain was brief heat stimulation applied to the left volar of 34 healthy volunteers . For conditioning , the right h and was immersed in 46.5 ° C water . Distraction was provided by three different difficulty levels of continuous cognitive visual tasks . Experimental blocks consisted of test pain : ( 1 ) alone ; ‘ baseline ’ , ( 2 ) with conditioning pain ; ‘ CPM ’ , ( 3 ) with distraction ; ‘ distraction ’ and ( 4 ) with conditioning pain and distraction ; ‘ combined ’ . They were r and omized and repeated three times and pain intensity and unpleasantness rated . Results showed an overall effect of experimental block on test pain intensity ( P = 0.0125 ) . Post‐hoc tests revealed a significant reduction in pain intensity ratings under Combined ( 21.2 ± 2.3 ; mean ± SEM ) compared to CPM alone ( 16.0 ± 2.3 ) ( P < 0.05 ) . Furthermore , at all levels of distraction there were always a few subjects who were not distracted despite expressing CPM . Based on the additive effect of CPM and distraction on pain inhibition , and the cases of no distraction despite CPM , we suggest that CPM acts independently from distraction The aim of this study was to evaluate the function of pain modulating systems subserving diffuse noxious inhibitory controls ( DNICs ) in primary headaches . DNICs were examined in 24 migraineurs , 17 patients with chronic tension-type headache ( CTTH ) and 20 healthy subjects by means of nociceptive flexion RIII reflex and the cold pressor test ( CPT ) as heterotopic noxious conditioning stimulation ( HNCS ) . The subjective pain thresholds ( Tp ) and the RIII reflex threshold ( Tr ) were significantly lower in CTTH vs. controls . In controls a significant inhibition of the RIII reflex was observed during the CPT ( -30± , P < 0.05 ) . Conversely , migraine and CTTH patients showed facilitation ( + 31± , P < 0.05 and + 40± , P < 0.01 , respectively ) of the RIII reflex during the HNCS . This study demonstrates a dysfunction in systems subserving DNICs in both migraine and CTTH . Impairment of endogenous supraspinal pain modulation systems may contribute to the development and /or maintenance of central sensitization in primary headaches UNLABELLED Pain catastrophizing is among the most robust predictors of pain outcomes , and a disruption in endogenous pain-inhibitory systems is 1 potential mechanism that may account for increased pain among individuals who report higher pain catastrophizing . Pain catastrophizing may negatively influence diffuse noxious inhibitory controls ( DNIC ) , a measure of endogenous pain inhibition , through complex anatomical circuitry linking cortical responses to pain with processes that modulate pain . The current study examined whether DNIC mediated the relationship between catastrophizing and pain among 35 healthy young adults and examined the moderating effects of sex to determine whether the magnitude or direction of associations differed among men and women . DNIC was assessed using pressure pain thresholds on the forearm before and during a cold pressor task . Using bias-corrected bootstrapped confidence intervals , results showed that diminished DNIC was a significant partial mediator of the relation between greater pain-related catastrophizing and more severe pain ratings . Participant sex moderated these associations ; higher catastrophizing predicted lower DNIC for men and women , however , the effect of catastrophizing on pain ratings was partially mediated by DNIC for women only . These findings further support the primary role of pain catastrophizing in modulation of pain outcomes . PERSPECTIVE These findings support the hypothesis that the heightened pain reported by individuals higher in pain catastrophizing may be related to a disruption in the endogenous modulation of pain , operationalized by assessing DNIC . Whether interventions that reduce pain catastrophizing affect pain outcomes via effects on DNIC is in need of investigation ABSTRACT In 10 patients with central post‐stroke pain ( CPSP ) , the influence of ischemia‐induced heterotopic noxious conditioning stimulation ( HNCS ) on the intensity of spontaneous ongoing‐ and brush‐evoked pain was examined . In addition , the modulating effect of ongoing pain and HNCS on pain sensitivity in a remote pain‐free area was explored . A semi‐quantitative brushing technique was employed in combination with a computerized visual analogue scale ( VAS ) to monitor the allodynic percept over time , by calculating the area under the VAS curve as the total brush‐evoked pain intensity . Heat‐ and pressure pain thresholds and sensitivity to suprathreshold heat‐ and pressure pain in the pain‐free area were assessed before and during HNCS . No significant alterations of ongoing‐ or brush‐evoked pain were found during HNCS , although 6 of 10 patients rated a reduction of about 50 % of the brush‐evoked pain . At baseline significantly increased pressure pain sensitivity ( threshold P < 0.05 ; suprathreshold P = 0.05 ) were demonstrated in patients compared to controls . During HNCS , higher pressure pain thresholds were demonstrated in patients and controls alike ( P < 0.001 ) , whereas in controls only decreased sensitivity to suprathreshold pressure pain was found ( P < 0.05 ) . Lack of influence from HNCS on ongoing‐ and brush‐evoked pain on a group level , indicates inability of modulation from endogenous pain controlling systems on nociceptive activity generated in the brain . Increased pressure pain sensitivity at baseline suggests alteration in corticofugal control of nociceptive sensitivity due to the brain lesion , whereas patients during HNCS seemed to activate modulatory systems interacting with nociceptive input from the spinal level equal to controls & NA ; Visceral pain processing is abnormal in a majority of irritable bowel syndrome ( IBS ) patients . Aberrant endogenous nociceptive modulation and anticipation are possible underlying mechanisms investigated in the current study . Twelve IBS patients and 12 matched healthy controls underwent brain fMRI scanning during the following r and omised stimuli : sham and painful rectal distensions by barostat without and with simultaneous activation of endogenous descending nociceptive inhibition using ice water immersion of the foot for heterotopic stimulation . Heterotopic stimulation decreased rectal pain scores from 3.7 ± 0.2 to 3.1 ± 0.3 ( mean ± SE , scale 0–5 ) in controls ( p < 0.01 ) , but not significantly in IBS . Controls differed from IBS patients in showing significantly greater activation bilaterally in the anterior insula , SII and putamen during rectal stimulation alone compared to rectal plus heterotopic stimulation . Greater activation during rectal plus heterotopic versus rectal stimulation was seen bilaterally in SI and the right superior temporal gyrus in controls and in the right inferior lobule and bilaterally in the superior temporal gyrus in IBS . Rectal pain scores were similarly low during sham stimulation in both groups , but brain activation patterns differed . In conclusion , IBS patients showed dysfunctional endogenous inhibition of pain and concomitant aberrant activation of brain areas involved in pain processing and integration . Anticipation of rectal pain was associated with different brain activation patterns in IBS involving multiple interoceptive , homeostatic , associative and emotional areas , even though pain scores were similar during sham distension . The aberrant activation of endogenous pain inhibition appears to involve circuitry relating to anticipation as well as pain processing itself Impaired central pain modulation is implicated in the pathophysiology of chronic pain . In this controlled experiment , we evaluated whether partial sleep loss altered endogenous pain inhibition and reports of spontaneous pain . Thirty-two healthy females were studied polysomnographically for 7 nights . On Nights 1 - 2 ( Baseline ) , subjects slept undisturbed for 8 hours . After Night 2 , subjects were r and omized to Control ( N = 12 ) , Forced Awakening ( FA , N = 10 ) , or Restricted Sleep Opportunity ( RSO , N = 10 ) conditions . Controls continued to sleep undisturbed . FA underwent 8 forced awakenings ( one per hour ) on Nights 3 - 5 . RSO subjects were yoked to FA on total sleep time ( TST ) , receiving partial sleep deprivation by delayed bedtime . On Night 6 , both FA & RSO underwent 36 hours total sleep deprivation ( TSD ) , followed by 11-hour recovery sleep ( Night 7 ) . Subjects completed twice-daily psychophysical assessment s of mechanical pain thresholds and pain inhibition ( Diffuse Noxious Inhibitory Controls ) , via use of a conditioning stimulus ( i.e. , cold pressor ) paradigm . FA and RSO demonstrated 50 % reductions in total sleep time and increases in nonpainful somatic symptoms during partial sleep deprivation . While sleep deprivation had no effect on pain thresholds , during partial sleep deprivation the FA group demonstrated a significant loss of pain inhibition and an increase in spontaneous pain ; neither of the other 2 groups showed changes in pain inhibition or spontaneous pain during partial sleep deprivation . These data suggest that sleep continuity disturbance , but not simple sleep restriction , impairs endogenous pain-inhibitory function and increases spontaneous pain , supporting a possible pathophysiologic role of sleep disturbance in chronic pain UNLABELLED Persistent shoulder pain is a common complication after stroke . Its etiology and underlying mechanisms are not well understood and treatment is generally unsatisfactory . The objective of this study was to assess the role of central sensitization and disinhibition in chronic stroke patients with chronic PSSP ( n = 19 ) , pain-free stroke patients ( n = 29 ) , and healthy controls ( n = 23 ) . Positive and negative somatosensory symptoms and signs were assessed using clinical examination and electrical and mechanical quantitative sensory testing ( QST ) . Conditioned pain modulation ( CPM ) was assessed by comparing QST thresholds before and after applying a cold pressor test . Sensory abnormalities were more frequently observed and more severe in patients with PSSP , including positive signs such as allodynia at the affected side and generalized hyperalgesia at the unaffected side . CPM was similar in stroke patients and healthy controls . This study showed that chronic PSSP was associated with several positive and negative somatosensory signs , implicating a role for central sensitization and possibly for disinhibition . Since the causal relationship remains unclear , and may be related to either neuroplasticity induced by ongoing nociception as well as to the neuropathic brain lesion , prospect i ve studies are warranted . PERSPECTIVE The assessment of somatosensory symptoms and signs and endogenous pain modulation demonstrated a role for central sensitization and possibly for disinhibition in chronic PSSP . Prevention and treatment of PSSP could benefit from a more detailed analysis of both peripheral and central pain mechanisms OBJECTIVE To examine possible deficiencies in endogenous pain modulating mechanisms in fibromyalgia patients compared with matched pain-free control subjects . DESIGN /SUBJECTS/ METHODOLOGY : Pain reduction was investigated in 25 female patients with fibromyalgia and 26 age-matched healthy women using the diffuse noxious inhibitory controls ( DNIC ) paradigm . Tonic thermal stimuli at painful and nonpainful intensities , tailored to individual heat pain thresholds , were employed to induce pain inhibition . The anticipated effect was assessed by measuring the electrical pain threshold and detection threshold , using a double staircase method . Only nontender control points were stimulated ( thermode on the foot , electrodes on the inner forearm ) . RESULTS The patients with fibromyalgia had significantly lower heat pain thresholds than the healthy subjects , but similar electrical detection and pain thresholds . The repeatedly applied electrical stimuli result ed in a degree of perceptual adaptation that was similar between the two groups . However , concurrent tonic thermal stimuli , at both painful and nonpainful levels , significantly increased the electrical pain threshold in the healthy subjects but not in the fibromyalgia patients . The electrical detection threshold was not affected in either group . CONCLUSIONS Pain modulation , produced by a concurrent tonic stimulus in healthy persons , was not seen in the fibromyalgia group . The patients either had deficient pain modulation or were unable to tolerate a tonic stimulus intense enough to engage a modulatory process . It remains to be established whether the pain reduction found in the healthy subjects was the conventional DNIC effect , another effect ( e.g. , distraction ) , or a combination of both This double-blind , within-subjects experiment examined the effect of ingesting a large dose of caffeine on perceptions of leg muscle pain during moderate intensity cycling exercise . Low-caffeine-consuming college-aged males ( n = 16 ) ingested either caffeine ( 10 mg x kg(-1 ) body weight ) or placebo and 1 hour later completed 30 minutes of moderate intensity cycling exercise ( 60 % VO(2peak ) ) . The order of drug administration was counter-balanced . Perceptions of leg muscle pain as well as work rate , heart rate , and oxygen uptake ( VO(2 ) ) were recorded during exercise . Leg muscle pain ratings were significantly and moderately reduced after a high dose of caffeine . This observation suggests that prior reports showing caffeine improves endurance exercise performance might be partially explained by caffeine 's hypoal \n Output:\n " }, { "from": "agent", "value": "Analysis of moderator variables indicated a significant influence of participant gender and age on the effect size .\nIt is concluded that conditioned pain modulation is impaired in population s with chronic pain .\nPERSPECTIVE This review compared the efficacy of conditioned pain modulation between chronic pain and healthy population s. The finding of impaired modulation in the chronic pain groups highlights the dysfunction of endogenous pain modulatory mechanisms in this population" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: PURPOSE To prospect ively evaluate , with magnetic resonance ( MR ) imaging , long-term outcome of the brain after endovascular versus neurosurgical treatment for aneurysmal subarachnoid hemorrhage ( aSAH ) . MATERIAL S AND METHODS Institutional review board approval and informed consent were obtained . One hundred sixty-eight ( 77 men , 91 women ; mean age + /- st and ard deviation , 51 years + /- 13 ) patients were r and omly assigned to surgical versus endovascular treatment of the ruptured aneurysm with 138 ( 67 endovascular , 71 surgical ) MR examinations 1 year after aSAH . The presence , localization , volumes , and cause of lesions were analyzed with chi(2 ) , Mann-Whitney U , and Student t tests . Furthermore , correlation between MR-detectable brain parenchymal high-signal intensity ( SI ) lesions on T2- and intermediate-weighted MR images and neuropsychologic outcome was evaluated by using Spearman correlation coefficient . RESULTS Only 44 ( 31.9 % ) of 138 patients had no lesions associated with aSAH . According to intention to treat , lesions were more frequent after surgical rather than endovascular treatment , predominating in the frontal ( surgical : n = 50 , [ 70.4 % ] vs endovascular : n = 34 [ 50.7 % ] , P = .018 ) and temporal ( n = 34 [ 47.9 % ] vs n = 15 [ 22.4 % ] , P = .002 ) lobes . Only endovascular patients had subtentorial lesions ( n = 4 [ 6.0 % ] , P = .037 ) . Ischemic lesions in the parental artery territory were more frequent in surgical ( n = 33 [ 46.5 % ] ) than in endovascular ( n = 15 [ 22.4 % ] , P = .003 ) patients , with corresponding mean lesion volumes of 20.9 cm(3 ) + /- 46.5 versus 17.6 cm(3 ) + /- 35.8 ( P = .209 ) . Ischemic lesions in remote vascular territories were equal in frequency and size . Retraction injuries were common in the surgical ( n = 40 , [ 56.3 % ] ) treatment group . Ischemic lesion volumes correlated with neuropsychologic test scores . CONCLUSION Parenchymal high-SI lesions on T2- and intermediate-weighted MR images are more frequent after early surgical rather than endovascular treatment of the ruptured aneurysm , and lesion volumes correlate with the neuropsychologic test performance Objective To determine if ischaemia is a mechanism of early brain injury at the time of aneurysm rupture in subarachnoid haemorrhage ( SAH ) and if early MRI ischaemia correlates with admission clinical status and functional outcome . Methods In a prospect i ve , hypothesis-driven study patients with SAH underwent MRI within 0–3 days of ictus ( prior to vasospasm ) and a repeat MRI ( median 7 days ) . The volume and number of diffusion weighted imaging ( DWI ) positive/apparent diffusion coefficient ( ADC ) dark lesions on acute MRI were quantitatively assessed . The association of early ischaemia , admission clinical status , risk factors and 3-month outcome were analysed . Results In 61 patients with SAH , 131 MRI were performed . Early ischaemia occurred in 40 ( 66 % ) with a mean DWI/ADC volume 8.6 mL ( 0–198 mL ) and lesion number 4.3 ( 0–25 ) . The presence of any early DWI/ADC lesion and increasing lesion volume were associated with worse Hunt-Hess grade , Glasgow Coma Scale score and Acute Physiology and Chronic Health Evaluation II physiological subscores ( all p<0.05 ) . Early DWI/ADC lesions significantly predicted increased number and volume of infa rcts on follow-up MRI ( p<0.005 ) . At 3 months , early DWI/ADC lesion volume was significantly associated with higher rates of death ( 21 % vs 3 % , p=0.031 ) , death/severe disability ( modified Rankin Scale 4–6 ; 53 % vs 15 % , p=0.003 ) and worse Barthel Index ( 70 vs 100 , p=0.004 ) . After adjusting for age , Hunt-Hess grade and aneurysm size , early infa rct volume correlated with death/severe disability ( adjusted OR 1.7 , 95 % CI 1.0 to 3.2 , p=0.066 ) . Conclusions Early ischaemia is related to poor acute neurological status after SAH and predicts future ischaemia and worse functional outcomes . Treatments addressing acute ischaemia should be evaluated for their effect on outcome Background : Aneurysmal subarachnoid hemorrhage ( SAH ) and surgical clipping of intracranial aneurysms are associated with substantial morbidity and mortality . Objective : To compare cognitive outcome and structural damage in patients with aneurysmal SAH treated with surgical clipping or endovascular coiling . Methods : Forty case-matched pairs of patients with aneurysmal SAH treated by surgical clipping or endovascular coiling were prospect ively assessed by use of a battery of cognitive tests . Twenty-three case-matched pairs underwent MRI 1 year after the procedure . Matching was based on grade of SAH on admission , location of aneurysm , age , and premorbid IQ . Results : Both groups were impaired in all cognitive domains when compared with age-matched healthy control subjects . Comparison of cognitive outcome between the two groups indicated an overall trend toward a poorer cognitive outcome in the surgical group , which achieved significance in four tests . MRI showed focal encephalomalacia exclusively in the surgical group . This group also had a significantly higher incidence of single or multiple small infa rcts within the vascular territory of the aneurysm , but both groups had similar incidence of large infa rcts and global ischemic damage . Conclusion : Endovascular treatment may cause less structural brain damage than surgery and have a more favorable cognitive outcome . However , cognitive outcome appears to be dictated primarily by the complications of SAH OBJECTIVE To assess whether subarachnoid hemorrhage ( SAH ) and its treatment is followed by volume loss in temporomesial structures . METHODS One hundred fifty-five consecutive patients with aneurysmal SAH were r and omly assigned to surgical or endovascular treatment . Volumetric MRI was performed in 77 SAH patients with good or moderate clinical outcome 1 year after hemorrhage . A comprehensive neuropsychological test battery was used to evaluate the cognitive performance of the subjects . Thirty healthy individuals were imaged as MRI controls . RESULTS The normalized hippocampal ( HC ) volumes were 24.7/23.7 ( right/left ) , and the amygdaloid ( AM ) volumes were 21.0/20.5 in the matched control population . In SAH patients , the corresponding volumes were smaller , HC 23.2/21.3 ( p = 0.072/0.002 ) and AM 18.4/18.7 ( p = 0.012/0.045 ) . In addition , the AM ipsilateral to the ruptured aneurysm was smaller in patients who had undergone surgical treatment ( 15.7 ) vs endovascular treatment ( 20.3 ; p < 0.001 ) . Treatment modality did not significantly affect the measured HC volumes . The hippocampal but not amygdaloid volumes correlated with the scores of several neuropsychological tests . CONCLUSION Subarachnoid hemorrhage and its treatment may be followed by atrophy in temporomesial structures . A clear correlation was demonstrated between neuropsychological performance and reduced temporomesial volumes Introduction Volume measurements performed on brain MRI after aneurysmal subarachnoid hemorrhage ( aSAH ) may provide insight into the structural abnormalities that underlie the commonly occurring and persistent long-term functional deficits after aSAH . We examined the pattern of long-term cerebral structural changes on MRI in relation to known risk factors for poor functional outcome . Methods We studied MRI scans from 38 patients who received endovascular treatment and were not dependent for activities of daily life at 18 months after aSAH . Risk factors for poor functional outcome ( clinical condition , Hijdra score , and bicau date index on admission ; occurrence of hydrocephalus or delayed cerebral infa rct ion during hospitalization ) were related to supratentorial cerebral parenchymal and lateral ventricular volumes on MRI with linear regression analyses adjusted for age , sex , and intracranial volume . Results Clinical condition , Hijdra score , and bicau date index on admission were not related to cerebral parenchymal volume at 18 months . A higher bicau date index on admission was related to lateral ventricular enlargement at 18 months after aSAH ( Beta ; 95%CI : 0.51 ; 0.14↔0.88 ) . Delayed cerebral infa rct ion was related to smaller cerebral parenchymal volumes ( −0.14 ; −0.25↔−0.04 ) and to lateral ventricular enlargement ( 0.49 ; 0.16↔0.83 ) at 18 months . Conclusion Volume measurements of the brain are able to quantify patterns of long-term cerebral damage in relation to different risk factors after aSAH . Application of volumetric techniques may provide more insight into the heterogeneous underlying pathophysiological processes . After confirmation of these results in larger studies , volumetric measures might even be used as outcome measures in future treatment studies OBJECTIVE In the course of performing systematic review s on the prevalence of low back and neck pain , we required a tool to assess the risk of study bias . Our objectives were to ( 1 ) modify an existing checklist and ( 2 ) test the final tool for interrater agreement . STUDY DESIGN AND SETTING The final tool consists of 10 items addressing four domains of bias plus a summary risk of bias assessment . Two research ers tested the interrater agreement of the tool by independently assessing 54 r and omly selected studies . Interrater agreement overall and for each individual item was assessed using the proportion of agreement and Kappa statistic . RESULTS Raters found the tool easy to use , and there was high interrater agreement : overall agreement was 91 % and the Kappa statistic was 0.82 ( 95 % confidence interval : 0.76 , 0.86 ) . Agreement was almost perfect for the individual items on the tool and moderate for the summary assessment . CONCLUSION We have addressed a research gap by modifying and testing a tool to assess risk of study bias . Further research may be useful for assessing the applicability of the tool across different conditions OBJECTIVE To prospect ively determine temporal changes in regional cerebral perfusion in patients with acutely ( < 72 h ) ruptured cerebral aneurysms treated either endovascularly or surgically . METHODS Cerebral perfusion was measured both before and 1 week after treatment by use of a 99mTc-labeled ethyl-cysteine dimer and single-photon emission computed tomographic ( SPECT ) studies in 46 of 81 consecutive patients included in a prospect i ve r and omized study of early treatment of ruptured aneurysms . In addition to visual analysis of the SPECT images , corticocerebellar perfusion ratios were calculated for seven predefined bilateral regions . Late ischemic deficits were evaluated after 12 months by magnetic resonance imaging of the brain . RESULTS Acute perfusion deficits were commonly seen before treatment . In the visual comparison between the first and second SPECT studies , the number of new or enlarged deficits ( P = 0.006 ) and deficits that exp and ed from unilateral to bilateral ( P = 0.020 ) significantly increased in the surgical group but not in the endovascular group . In the second SPECT study , surgical patients had decreased corticocerebellar perfusion ratios in the right frontobasal cortex ( P = 0.012 ) compared with the endovascular patients , and in the ipsilateral frontobasal cortex ( P = 0.002 ) and ipsilateral temporal apex ( P = 0.002 ) compared with the contralateral side of the ruptured aneurysm . The 12-month magnetic resonance imaging of the brain revealed no significant difference in the number of ischemic deficits between the endovascular and surgical groups . CONCLUSION Disturbances in cerebral perfusion both before and after treatment are common . Although no major differences in the findings were detected between patients treated with either clips or coils , progression of perfusion deficits was more common in the surgical group . However , the 12-month magnetic resonance imaging of the brain revealed equal numbers of ischemic deficits in the treatment groups OBJECT The calcium antagonist nimodipine has been shown to reduce the incidence of ischemic complications following aneurysmal subarachnoid hemorrhage ( SAH ) . Although most r and omized studies have been focused on the effect of the peroral administration of nimodipine , intravenous infusion is an alternative and the preferred mode of treatment in many centers . It is unknown whether the route of administration is of any importance for the clinical efficacy of the drug . METHODS One hundred six patients with acute aneurysmal SAH were r and omized to receive either peroral or intravenous nimodipine treatment . The patients were monitored for at least 10 days \n Output:\n " }, { "from": "agent", "value": "The results according to aim , with levels of evidence , were : ( 1 ) 25 to 81 % of aneurysmal subarachnoid hemorrhage patients show infa rcts ( strong ) ; there is a higher ratio of cerebrospinal fluid-to-intracranial volume in patients compared to controls ( strong ) ; ( 2 ) there is a negative relation between age ( moderate ) , DCI ( low ) and brain volume measurement outcomes ; ( 3 ) lower brain parenchymal volume ( strong ) and the presence of infa rcts or infa rct volumes ( moderate ) are associated with a worse outcome .\nConclusion Patients after aneurysmal subarachnoid hemorrhage may demonstrate brain infa rcts and decreased brain parenchyma , which is related to worse outcome .\nThereby , both brain infa rcts and brain volume measurements could be used as outcome markers in pharmaceutical trials ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: The effect of oral oestriol ( 3 mg/day for 4 weeks followed by 2 mg/day for a further 6 weeks ) on the vaginal bacterial flora , vaginal cytology and urogenital symptoms was assessed in a double-blind , placebo-controlled study in 35 women with symptoms of the urogenital oestrogen deficiency syndrome . No significant differences were observed with regard to the occurrence or severity of urogenital symptoms , vaginal pH , karyopyknotic index ( KPI ) or the baseline results of vaginal bacterial cultures in the 18 patients ( mean age 71.6 + /- 1.0 years ) treated with oestriol and the 17 women ( mean age 72.6 + /- 1.4 years ) who received placebo tablets . A decrease in both vaginal pH ( P less than 0.001 ) and the proportion of faecal-type bacteria ( P less than 0.05 ) , and an increase in the KPI ( P less than 0.01 ) and the proportion of lactobacilli ( P less than 0.001 ) were recorded after 10 weeks of treatment with oral oestriol . At the end of the following 10 medication-free weeks all of these parameters except vaginal pH had returned to values that were not significantly altered from the corresponding baseline levels . In the patients treated with placebo no significant changes occurred in vaginal pH , KPI or the proportion of lactobacilli in vaginal cultures during the course of this study . Urogenital symptoms improved in both groups after medication ( and even after the medication-free period ) in relation to the baseline assessment , which reflects the latter 's subjective nature OBJECTIVE We studied the efficacy , safety , and acceptability of an estradiol-releasing ( 6.5 to 9.5 micrograms per 24 hours ) silicone vaginal ring ( Estring ) in postmenopausal women with symptoms and signs of urogenital aging during a treatment period of 1 year . STUDY DESIGN The study was open with blind analysis of vaginal cytologic testing . In addition to gynecologic examination , subjective symptoms were assessed and vaginal pH and urinary sample s ( for bacteriuria ) were obtained before insertion of Estring . This procedure was repeated every 3 months up to 1 year 's treatment , together with requests concerning acceptability and adverse experiences . At inclusion and end of Estring treatment , vaginal smears for evaluation of cytologic results were obtained . RESULTS Estring induced a high maturation value in the vaginal mucosa and restored vaginal pH to levels normality seen in fertile women ( < 5.5 ) . For most variables a 90 % responder rate ( proportion of cured and improved patients ) was found after 3 months and up to 1 year regarding subjective symptoms and objective signs of vaginal mucosal atrophy . Twenty-eight ( 20 % ) of 136 women , withdrew from the study , 8 ( 6 % ) of them because of adverse events . Three women reported vaginal bleeding , none associated with malignancy or endometrial proliferation . Ten ( 7 % ) reported vaginal irritation , and in two cases vaginal ulcers were found . About 90 % did not remove the ring during any of the 3-month treatment periods , and 78 % used the four consecutive rings continuously up to 1 year . The ring was given a strong preference ( p < 0.001 ) by patients with previous experience of other administration forms . CONCLUSION Estring represents a safe , highly effective , and very well-accepted administration form for long-term treatment of urogenital disorders caused by estrogen deficiency in postmenopausal women We compared the efficacy and safety of estriol-containing vaginal pessary use with those of oral nitrofurantoin macrocrystal ( NM ) therapy for preventing urinary tract infection ( UTI ) in postmenopausal women with recurrent UTI . Over a period of 9 months , 86 women received an estriol-containing vaginal pessary ( 0.5 mg estriol ) twice weekly , and 85 women received NM ( 100 mg ) once daily . We recorded 124 episodes of UTI in women who received estriol-releasing pessaries and 48 episodes of UTI in women treated with NM ( P=.0003 ) . Twenty-eight women ( 32.6 % ) who received estriol had no episodes of UTI versus 41 women ( 48.2 % ) in the NM group . There was a significant increase in the number of superficial cells in women who received estriol , whereas in the NM group , no such changes occurred . However , there was no change in the extent of Lactobacillus colonization and in the vaginal pH in women who received estriol . Use of an estriol-containing pessary is less effective than oral NM therapy in the prevention of bacteriuria in postmenopausal women because of its failure to restore the population of lactobacilli and to reduce the vaginal pH in these women OBJECTIVE The primary objective was to detect a difference in time until the first recurrence of urinary tract infection during treatment with an estradiol-releasing silicone vaginal ring ( Estring ; Pharmacia & Upjohn , Inc , Uppsala , Sweden ) compared with no estrogen treatment . The secondary objective was to detect any differences in improvement of urethral and vaginal mucosal atrophy and in the subjective assessment of urogenital symptoms . The study also sought to detect a difference in decrease of vaginal pH to < 5.5 and to record adverse events . STUDY DESIGN This was a multicenter , r and omized , open , parallel-group study with an untreated control group . Postmenopausal women with recurrent symptomatic , bacteriologically confirmed urinary tract infections were r and omly assigned to receive either Estring ( 2 mg estradiol ) or no estrogen treatment . One ring was carried vaginally for 12 weeks . The duration of treatment was 36 weeks for the Estring group and either 36 weeks or until the first recurrence for the control group . Both intent-to-treat and per- protocol analyses were performed to evaluate efficacy , whereas the safety analysis was limited to the intent-to-treat group . The primary variable was analyzed by survival analysis with the Kaplan-Meier method for estimating the survival density function . To compare the survival curves for the 2 treatment groups a log-rank test was performed for time until first recurrence . RESULTS A total of 108 women were r and omly assigned , 53 to the Estring group and 55 to the control group . The cumulative proportion of women remaining free of urinary tract infection was significantly higher in the Estring group than in the control group ( P = .008 ) . After 36 weeks of study the cumulative likelihood of remaining free of disease was approximately 45 % in the women with the vaginal ring compared with approximately 20 % in the control group . Estring lowered vaginal pH , and the time to first recurrence was effectively prolonged by Estring treatment . Vaginal and , to a lesser extent , urethral mucosal cells were significantly more mature in the Estring group . No unexpected adverse events were found . CONCLUSION Estring is useful to prolong the time to next recurrence among postmenopausal women with recurrent urinary tract infection and to decrease the number of recurrences per year . The silicone vaginal ring also has a clinical ly significant ability to alleviate other postmenopausal urogenital symptoms . Estring is safe and well tolerated To evaluate factors associated with recurrent urinary tract infection ( UTI ) in postmenopausal women , we conducted a case-control study comparing 149 postmenopausal women referred to an infectious diseases outpatient clinic who had a history of recurrent UTI ( case patients ) with 53 age-matched women without a history of UTI ( control patients ) . Each woman completed a question naire providing demographic data , history and clinical characteristics of prior infections , and information regarding risk factors for UTI . In addition , each patient underwent a gynecologic evaluation , renal ultrasound and urine flow studies , and blood group and secretor status testing . Three urologic factors-namely , incontinence ( 41 % of case patients vs. 9.0 % of control patients ; P<.001 ) , presence of a cystocele ( 19 % vs. 0 % ; P<.001 ) , and postvoiding residual urine ( 28 % vs. 2.0 % ; P=.00008)-were all strongly associated with recurrent UTI . Multivariate analysis showed that urinary incontinence ( odds ratio [ OR ] , 5.79 ; 95 % confidence interval [ CI ] , 2.05 - 16.42 ; P=.0009 ) , a history of UTI before menopause ( OR , 4.85 ; 95 % CI , 1.7 - 13.84 ; P=. 003 ) , and nonsecretor status ( OR , 2.9 ; 95 % CI , 1.28 - 6.25 ; P=.005 ) were most strongly associated with recurrent UTI in postmenopausal women . Prospect i ve studies are needed to confirm these observations and to develop approaches for prevention To determine whether the combined contraceptive pill used intravaginally was as effective as the st and ard conjugated estrogen cream for the treatment of urogenital symptoms in postmenopausal Thai women OBJECTIVE Estrogen or combined hormone ( estrogen-progestin ) therapy is highly efficacious for managing the signs and symptoms of urogenital atrophy . A low , effective estrogen dose may enhance patient acceptance and reduce side effects . METHODS In this r and omized , double-blind , multicenter clinical trial , 71 healthy postmenopausal women with vaginal atrophy ( Vaginal Maturation Index < or = 55 ) received either low-dose synthetic conjugated estrogens , A tablets ( Cenestin ) ( SCE-A ) , 0.3 mg once daily , or placebo for 16 weeks . RESULTS Treatment with SCE-A for 16 weeks result ed in a highly significant ( P<0.0001 ) mean increase of 17.7 in the Vaginal Maturation Index compared to a mean increase of 4.1 with placebo treatment . A significant estrogenic improvement was detected as early as 4 weeks ( mean increase 14.6 ) . Superficial cells were significantly increased from 2.1 % at baseline to 15.9 % at week 16 with SCE-A , and parabasal cells were significantly reduced from 23.0 % at baseline to 1.6 % at week 16 ( P<0.01 between treatments for both ) . Vaginal pH was significantly decreased from 6.2 at week -2 to 5.2 at week 16 with SCE-A compared to placebo ( P<0.0001 ) . There were no significant differences between treatment groups in the incidence of treatment-emergent side effects or other measures of safety , except for urinary tract infection , which occurred more frequently in the placebo group . CONCLUSIONS These results confirm the relatively rapid estrogenic effect and safety of a low-dose ( 0.3 mg/day ) of slow-release SCE-A ( Cenestin ) in the treatment of vaginal atrophy in postmenopausal women A block r and omized , double-blind , group-comparative , placebo-controlled study was conducted to assess the effect of oestriol on recurrent urinary tract infections in postmenopausal women . 40 women , median age 78 years ( 66 - 91 ) , 20 in each group , were treated with oestriol three mg p.o . per day or corresponding placebo for four weeks , followed by one mg per day for eight weeks . The main response parameter was the number of urinary tract infections per week in the two treatment periods . Both oestriol and placebo reduced the number of infections per week significantly in both periods , compared with the pretreatment period . There was no difference between oestriol and placebo treatment in the first period . In the second period , however , oestriol treatment was significantly more effective than placebo ( p = 0.05 ) . Correspondingly , there was a significant difference between the two groups in the vaginal pH at the end of the study ( p less than 0.05 ) . We conclude that oestriol reduces recurrent urinary tract infections in postmenopausal women BACKGROUND Recurrent urinary tract infections are a problem for many postmenopausal women . Estrogen replacement restores atrophic mucosa , lowers vaginal pH , and may prevent urinary tract infections . METHODS We enrolled 93 postmenopausal women with a history of recurrent urinary tract infections in a r and omized , double-blind , placebo-controlled trial of a topically applied intravaginal estriol cream . Midstream urine cultures were obtained at enrollment , monthly for eight months , and whenever urinary symptoms occurred . Vaginal cultures and pH measurements were obtained at entry and after one and eight months . The women were assigned to receive either estriol ( n = 50 ) or placebo ( n = 43 ) , both administered intravaginally ; 36 and 24 , respectively , completed the eight months of follow-up . RESULTS The incidence of urinary tract infection in the group given estriol was significantly reduced as compared with that in the group given placebo ( 0.5 vs. 5.9 episodes per patient-year , P < 0.001 ) . Survival analysis showed that more of the women in the estriol group than in the placebo group remained free of urinary tract infection ( P < 0.001 ) . Lactobacilli were absent in all vaginal cultures \n Output:\n " }, { "from": "agent", "value": "AUTHORS ' CONCLUSIONS Based on only two studies comparing vaginal oestrogens to placebo , vaginal oestrogens reduced the number of UTIs in postmenopausal women with RUTI , however this varied according to the type of oestrogen used and the treatment duration" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Objectives : To evaluate the effect of hormonal contraception including combined oral contraceptives ( COCs ) , and the injectable progestins depo-medroxyprogesterone acetate ( DMPA ) and norethisterone enanthate ( Net-En ) on the risk of HIV acquisition among women in South Africa . Design / methods : We analyzed data from 5567 women aged 16–49 years participating in the Carraguard Phase 3 Efficacy Trial . Participants were interviewed about contraceptive use and sexual behaviors and underwent pelvic examinations and HIV testing quarterly . We used marginal structural Cox regression models to estimate the effect of hormonal contraception exposure on HIV acquisition risk among women overall and among young women ( 16–24 years ) in particular . Results : Two hundred and seventy participants became HIV-infected ( 3.7 per 100 woman-years ) ; HIV incidence was 2.8 , 4.6 , 3.5 and 3.4 per 100 woman-years in the COC , DMPA , Net-En and nonhormonal contraceptive groups , respectively ( P = 0.09 ) . The adjusted hazard ratios ( AHRs ) were 0.84 [ 95 % confidence interval ( CI ) 0.51–1.39 ] , 1.28 ( 95 % CI 0.92–1.78 ) and 0.92 ( 95 % CI 0.64–1.32 ) among COC , DMPA and Net-En users , respectively , compared with the nonhormonal group controlling for covariates . Age modified the effect of hormonal contraception on HIV acquisition risk ; among young women , the AHRs were 1.02 ( 95 % CI 0.46–2.28 ) for COCs , 1.68 ( 95 % CI 0.96–2.94 ) for DMPA and 1.36 ( 95 % CI0.78–2.35 ) for Net-En users . Conclusions : In this study conducted among South African women , hormonal contraception did not significantly increase the risk of HIV acquisition . However , the effect estimate does not rule out a moderate increase in HIV risk associated with DMPA use found in some other recent studies BACKGROUND Hormonal contraceptives are used widely but their effects on HIV-1 risk are unclear . We aim ed to assess the association between hormonal contraceptive use and risk of HIV-1 acquisition by women and HIV-1 transmission from HIV-1-infected women to their male partners . METHODS In this prospect i ve study , we followed up 3790 heterosexual HIV-1-serodiscordant couples participating in two longitudinal studies of HIV-1 incidence in seven African countries . Among injectable and oral hormonal contraceptive users and non-users , we compared rates of HIV-1 acquisition by women and HIV-1 transmission from women to men . The primary outcome measure was HIV-1 seroconversion . We used Cox proportional hazards regression and marginal structural modelling to assess the effect of contraceptive use on HIV-1 risk . FINDINGS Among 1314 couples in which the HIV-1-seronegative partner was female ( median follow-up 18·0 [ IQR 12·6 - 24·2 ] months ) , rates of HIV-1 acquisition were 6·61 per 100 person-years in women who used hormonal contraception and 3·78 per 100 person-years in those who did not ( adjusted hazard ratio 1·98 , 95 % CI 1·06 - 3·68 , p=0·03 ) . Among 2476 couples in which the HIV-1-seronegative partner was male ( median follow-up 18·7 [ IQR 12·8 - 24·2 ] months ) , rates of HIV-1 transmission from women to men were 2·61 per 100 person-years in couples in which women used hormonal contraception and 1·51 per 100 person-years in couples in which women did not use hormonal contraception ( adjusted hazard ratio 1·97 , 95 % CI 1·12 - 3·45 , p=0·02 ) . Marginal structural model analyses generated much the same results to the Cox proportional hazards regression . INTERPRETATION Women should be counselled about potentially increased risk of HIV-1 acquisition and transmission with hormonal contraception , especially injectable methods , and about the importance of dual protection with condoms to decrease HIV-1 risk . Non-hormonal or low-dose hormonal contraceptive methods should be considered for women with or at-risk for HIV-1 . FUNDING US National Institutes of Health and the Bill & Melinda Gates Foundation The past decade has seen the rise of evidence -based medicine , a movement that has focused attention on the importance of using clinical studies for empirical demonstration of the efficacy of medical interventions . Increasingly , physicians are being called on to assess such studies to help them make clinical decisions and underst and the rationale behind recommended practice s. This type of assessment requires an underst and ing of research methods that until recently was not expected of physicians . These research methods include statistical techniques used to assist in drawing conclusions . However , the methods of statistical inference in current use are not evidence -based and thus have contributed to a widespread misperception . The misperception is that absent any consideration of biological plausibility and prior evidence , statistical methods can provide a number that by itself reflects a probability of reaching erroneous conclusions . This belief has damaged the quality of scientific reasoning and discourse , primarily by making it difficult to underst and how the strength of the evidence in a particular study can be related to and combined with the strength of other evidence ( from other laboratory or clinical studies , scientific reasoning , or clinical experience ) . This results in many knowledge cl aims that do not st and the test of time ( 1 , 2 ) . A pair of articles in this issue examines this problem in some depth and proposes a partial solution . In this article , I explore the historical and logical foundations of the dominant school of medical statistics , sometimes referred to as frequentist statistics , which might be described as error-based . I explicate the logical fallacy at the heart of this system and the reason that it maintains such a tenacious hold on the minds of investigators , policymakers , and journal editors . In the second article ( 3 ) , I present an evidence -based approach derived from Bayesian statistical methods , an alternative perspective that has been one of the most active areas of biostatistical development during the past 20 years . Bayesian methods have started to make inroads into medical journals ; Annals , for example , has included a section on Bayesian data interpretation in its Information for Authors section since 1 July 1997 . The perspective on Bayesian methods offered here will differ somewhat from that in previous presentations in other medical journals . It will focus not on the controversial use of these methods in measuring belief but rather on how they measure the weight of quantitative evidence . We will see how reporting an index called the Bayes factor ( which in its simplest form is also called a likelihood ratio ) instead of the P value can facilitate the integration of statistical summaries and biological knowledge and lead to a better underst and ing of the role of scientific judgment in the interpretation of medical research . An Example of the Problem A recent r and omized , controlled trial of hydrocortisone treatment for the chronic fatigue syndrome showed a treatment effect that neared the threshold for statistical significance , P=0.06 ( 4 ) . The discussion section began , hydrocortisone treatment was associated with an improvement in symptoms This is the first such study to demonstrate improvement with a drug treatment of [ the chronic fatigue syndrome ] ( 4 ) . What is remarkable about this paper is how unremarkable it is . It is typical of many medical research reports in that a conclusion based on the findings is stated at the beginning of the discussion . Later in the discussion , such issues as biological mechanism , effect magnitude , and supporting studies are presented . But a conclusion is stated before the actual discussion , as though it is derived directly from the results , a mere linguistic transformation of P=0.06 . This is a natural consequence of a statistical method that has almost eliminated our ability to distinguish between statistical results and scientific conclusions . We will see how this is a natural outgrowth of the P value fallacy . Philosophical Preliminaries To begin our exploration of the P value fallacy , we must consider the basic elements of reasoning . The process that we use to link underlying knowledge to the observed world is called inferential reasoning , of which there are two logical types : deductive inference and inductive inference . In deductive inference , we start with a given hypothesis ( a statement about how nature works ) and predict what we should see if that hypothesis were true . Deduction is objective in the sense that the predictions about what we will see are always true if the hypotheses are true . Its problem is that we can not use it to exp and our knowledge beyond what is in the hypotheses . Inductive inference goes in the reverse direction : On the basis of what we see , we evaluate what hypothesis is most tenable . The concept of evidence is inductive ; it is a measure that reflects back from observations to an underlying truth . The advantage of inductive reasoning is that our conclusions about unobserved states of nature are broader than the observations on which they are based ; that is , we use this reasoning to generate new hypotheses and to learn new things . Its drawback is that we can not be sure that what we conclude about nature is actually true , a conundrum known as the problem of induction ( 5 - 7 ) . From their clinical experience , physicians are acutely aware of the subtle but critical difference between these two perspectives . Enumerating the frequency of symptoms ( observations ) given the known presence of a disease ( hypothesis ) is a deductive process and can be done by a medical student with a good medical textbook ( Figure 1 , top ) . Much harder is the inductive art of differential diagnosis : specifying the likelihood of different diseases on the basis of a patient 's signs , symptoms , and laboratory results . The deductions are more certain and objective but less useful than the inductions . Figure 1 . The parallels between the processes of induction and deduction in medical inference ( top ) and statistical inference ( bottom ) . The identical issue arises in statistics . Under the assumption that two treatments are the same ( that is , the hypothesis of no difference in efficacy is true ) , it is easy to calculate deductively the frequency of all possible outcomes that we could observe in a study ( Figure 1 , bottom ) . But once we observe a particular outcome , as in the result of a clinical trial , it is not easy to answer the more important inductive question , How likely is it that the treatments are equivalent ? In this century , philosophers have grappled with the problem of induction and have tried to solve or evade it in several ways . Karl Popper ( 8) proposed a philosophy of scientific practice that eliminated formal induction completely and used only the deductive elements of science : the prediction and falsification components . Rudolf Carnap tried an opposite strategy to make the inductive component as logically secure as the deductive part ( 9 , 10 ) . Both were unsuccessful in producing workable models for how science could be conducted , and their failures showed that there is no method ologic solution to the problem of fallible scientific knowledge . Determining which underlying truth is most likely on the basis of the data is a problem in inverse probability , or inductive inference , that was solved quantitatively more than 200 years ago by the Reverend Thomas Bayes . He withheld his discovery , now known as Bayes theorem ; it was not divulged until 1762 , 20 years after his death ( 11 ) . Figure 2 shows Bayes theorem in words . Figure 2 . Bayes theorem , in words . As a mathematical equation , Bayes theorem is not controversial ; it serves as the foundation for analyzing games of chance and medical screening tests . However , as a model for how we should think scientifically , it is criticized because it requires assigning a prior probability to the truth of an idea , a number whose objective scientific meaning is unclear ( 7 , 10 , 12 ) . It is speculated that this may be why Reverend Bayes chose the more dire of the publish or perish options . It is also the reason why this approach has been tarred with the subjective label and has not generally been used by medical research ers . Conventional ( Frequentist ) Statistical Inference Because of the subjectivity of the prior probabilities used in Bayes theorem , scientists in the 1920s and 1930s tried to develop alternative approaches to statistical inference that used only deductive probabilities , calculated with mathematical formulas that described ( under certain assumptions ) the frequency of all possible experimental outcomes if an experiment were repeated many times ( 10 ) . Methods based on this frequentist view of probability included an index to measure the strength of evidence called the P value , proposed by R.A. Fisher in the 1920s ( 13 ) , and a method for choosing between hypotheses , called a hypothesis test , developed in the early 1930s by the mathematical statisticians Jerzy Neyman and Egon Pearson ( 14 ) . These two methods were incompatible but have become so intertwined that they are mistakenly regarded as part of a single , coherent approach to statistical inference ( 6 , 15 , 16 ) . The P Value The P value is defined as the probability , under the assumption of no effect or no difference ( the null hypothesis ) , of obtaining a result equal to or more extreme than what was actually observed ( Figure 3 ) . Fisher proposed it as an informal index to be used as a measure of discrepancy between the data and the null hypothesis . It was not part of a formal inferential method . Fisher suggested that it be used as part of the fluid , non-quantifiable process of drawing conclusions from observations , a process that included combining the P value in some unspecified way with background information ( 17 ) . Figure 3 . The bell-shaped curve represents the probability of every possible outcome under the null hypothesis . P P It is worth noting one widely The use of hormonal contraception has been associated with an increased risk of HIV-1 in some studies but not in others . We analysed data from a 10-year prospect i ve cohort study of female sex workers in Mombasa , Kenya . In multivariate analysis , women using the injectable contraceptive depot medroxyprogesterone acetate and women using oral contraceptive pills were at increased risk of HIV-1 acquisition compared with women using no contraceptive method \n Output:\n " }, { "from": "agent", "value": "Thus , some , but not all , observational data raise concern about a potential association between use of DMPA and risk of HIV acquisition ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Background Persistent pain is a challenging clinical problem after breast cancer treatment . After surgery , inflammatory pain and nociceptive input from nerve injury induce central sensitization which may play a role in the genesis of persistent pain . Using quantitative sensory testing , we tested the hypothesis that adding COX-2 inhibition to st and ard treatment reduces hyperalgesia after breast cancer surgery . A secondary hypothesis was that patients developing persistent pain would exhibit more postoperative hyperalgesia . Methods 138 women scheduled for lumpectomy/mastectomy under general anesthesia with paravertebral block were r and omized to COX-2 inhibition ( 2x40 mg parecoxib on day of surgery , thereafter 2x200 mg celecoxib/day until day five ) or placebo . Preoperatively and 1 , 5 , 15 days and 1 , 3 , 6 , 12 months postoperatively , we determined electric and pressure pain tolerance thresholds in dermatomes C6/T4/L1 and a 100 mm VAS score for pain . We calculated the sum of pain tolerance thresholds and analyzed change in these versus preoperatively using mixed models analysis with factor medication . To assess hyperalgesia in persistent pain patients we performed an additional analysis on patients reporting VAS>30 at 12 months . Results 48 COX-2 inhibition and 46 placebo patients were analyzed in a modified intention to treat analysis . Contrary to our primary hypothesis , change in the sum of tolerance thresholds in the COX-2 inhibition group was not different versus placebo . COX-2 inhibition had an effect on pain on movement at postoperative day 5 ( p<0.01 ) . Consistent with our secondary hypothesis , change in sum of pressure pain tolerance thresholds in 11 patients that developed persistent pain was negative versus patients without pain ( p<0.01 ) from day 5 to 1 year postoperatively . Conclusions Perioperative COX-2 inhibition has limited value in preventing sensitization and persistent pain after breast cancer surgery . Central sensitization may play a role in the genesis of persistent postsurgical pain Background : Regional anesthesia improves postoperative analgesia and enhances quality of recovery ( QoR ) after ambulatory surgery . This r and omized , double-blinded , parallel-group , placebo-controlled trial examines the effects of multilevel ultrasound-guided paravertebral blocks ( PVBs ) and total intravenous anesthesia on QoR after ambulatory breast tumor resection . Methods : Sixty-six women were r and omized to st and ardized general anesthesia ( control group ) or PVBs and propofol-based total intravenous anesthesia ( PVB group ) . The PVB group received T1–T5 PVBs with 5 ml of 0.5 % ropivacaine per level , whereas the control group received sham subcutaneous injections . Postoperative QoR was design ated as the primary outcome . The 29-item ambulatory QoR tool was administered in the preadmission clinic , before discharge , and on postoperative days 2 , 4 , and 7 . Secondary outcomes included block success , pain scores , intra- and postoperative morphine consumption , time to rescue analgesia , incidence of nausea and vomiting , and hospital discharge time . Results : Data from sixty-four patients were analyzed . The PVB group had higher QoR scores than control group upon discharge ( 146 vs. 131 ; P < 0.0001 ) and on postoperative day 2 ( 145 vs. 135 ; P = 0.013 ) ; improvements beyond postoperative day 2 lacked statistical significance . None of the PVB group patients required conversion to inhalation gas – based general anesthesia or experienced block-related complications . PVB group patients had improved pain scores on postanesthesia care unit admission and discharge , hospital discharge , and postoperative day 2 ; their intraoperative morphine consumption , incidence of nausea and vomiting , and discharge time were also reduced . Conclusion : Combining multilevel PVBs with total intravenous anesthesia provides reliable anesthesia , improves postoperative analgesia , enhances QoR , and expedites discharge compared with inhalational gas- and opioid-based general anesthesia for ambulatory breast tumor resection BACKGROUND : The efficacy of continuous wound infiltration with local anesthetic has not been compared with that of thoracic paravertebral block ( PVB ) after breast surgery . In this study , we evaluated the analgesic efficacy and morphine consumption of the two techniques after mastectomy . METHODS : Forty-eight patients undergoing modified radical mastectomy with axillary dissection were r and omly assigned to either a preoperative PVB with 20 mL of ropivacaine 0.5 % ( group PVB ) or a continuous ropivacaine 0.5 % infusion ( CRI ) at a 2 mL/h rate for each of two multilumen catheters placed subcutaneously at the end of the procedure ( group CRI ) . The catheters were left in place for 24 h postoperatively . A st and ardized general anesthetic was administered to all patients . Postoperative morphine consumption , pain scores and painful restricted movement of the shoulder for 24 h postoperatively as well as incidence of adverse events , including postoperative nausea and vomiting , were recorded . RESULTS : Morphine consumption was similar between groups ( PVB : 42.6 ± 11 vs CRI : 38.7 ± 11 mg in 24 h , P = 0.225 ) . Absolute pain scores were low in both groups . Four hours after surgery , group PVB showed a significant reduction in postoperative pain ( PVB : 0 [ 0–10 ] vs CRI : 0 [ 0–30 ] , P = 0.002 ) and reduced painful restricted movement ( P = 0.004 ) , whereas the CRI group had lower pain scores ( PVB : 10 [ 0–30 ] vs CRI : 0 [ 0–20 ] , P = 0.034 ) and painful restricted movement ( P = 0.043 ) 16 and 24 h ( PVB : 10 [ 0–30 ] vs CRI : 0 [ 0–30 ] , P = 0.012 ) after surgery . Postoperative nausea and vomiting was significantly more frequent in the CRI group ( P = 0.017 ) . CONCLUSIONS : Continuous wound infiltration of local anesthetics is an effective alternative to paravertebral analgesia after mastectomy with axillary dissection Background The pectoral nerves ( PECS ) block can not block the most internal mammary region , whereas a transversus thoracic muscle plane ( TTP ) block can . The combination of PECS and TTP blocks may be suitable for anterior chest surgery . We studied patients undergoing mastectomy to assess whether the combination of PECS and TTP blocks provides better analgesia than PECS block alone . Methods Seventy adult female patients undergoing unilateral mastectomy under general anaesthesia were r and omly allocated to receive either the combination of PECS and TTP blocks ( PT group , n=35 ) or the PECS block only ( C group , n=35 ) . The primary outcome measure was visual analog scale pain score . Secondary outcomes were the sensory level loss confirmed by cold tests and additional analgesic drugs within 24 h after the operation . Results The visual analog scale pain scores were lower in the PT group than the C group . The use of postoperative additional analgesic drugs was also lower lower in the PT group than that in the C group . In the majority of patients in the PT group , sensory loss was confirmed in both the anterior and the lateral branches of thoracic nerves ( Th2–6 ) . Conclusion Compared with PECS block , the combination of PECS and TTP blocks provides effective perioperative pain relief for breast cancer surgery . Clinical trial registration University Hospital Medical Information Network ( UMIN ) ID number 000018299 Avoidance of general anaesthesia for breast surgery may be because of clinical reasons or patient choice . There is emerging evidence that the use of regional anaesthesia and the avoidance of volatile anaesthetics and opioid analgesia may have beneficial effects on oncological outcomes . We conducted a prospect i ve observational case series of 16 breast cancer surgeries performed under thoracic paravertebral plus pectoral nerve block with propofol sedation to demonstrate feasibility of technique , patient acceptability and surgeon satisfaction . Fifteen out of 16 cases were successfully completed under sedation and regional anaesthesia , with one conversion to general anaesthesia . Eleven out of 16 cases required low‐dose intra‐operative opioid analgesia . Out of the 15 surgical procedures completed under regional anaesthesia with sedation , all patients experienced either no or minimal intra‐operative pain , and all would choose this anaesthetic technique again . Surgeon‐reported operating conditions were ‘ indistinguishable from general anaesthesia ’ in most cases , and surgeons were ‘ extremely satisfied ’ or ‘ satisfied ’ with the technique after every procedure . Combined thoracic paravertebral plus pectoral nerve block with intra‐operative sedation is a feasible technique for breast surgery Background and Objectives Serratus plane block is performed for analgesia of the anterior chest wall . However , there has been no study concerning the appropriate volume for this block . This prospect i ve r and omized controlled study assesses the dermatomal spread and analgesic effects of serratus plane block . Methods Ultrasound-guided serratus plane block was performed for breast cancer surgery . The patients were r and omly assigned to receive 20 or 40 mL of 0.375 % ropivacaine . The primary end point was the number of affected dermatomes as assessed by cold test and pinprick test 20 minutes after the block procedure . Secondary end points were the time until the first postoperative analgesic rescue , adverse effects , and complications . Results The number of affected dermatomes assessed by the cold test for patients receiving 40 mL of 0.375 % ropivacaine was significantly larger than that for patients receiving 20 mL ( P = 0.002 ; 6 [ 5–7 ] vs 4 [ 3–4 ] dermatomes ) . Similarly , with the pinprick test , the affected area was larger for the 40 mL group than for the 20 mL group ( P = 0.009 ; 4 [ 2–6 ] vs 2 [ 1–3 ] dermatomes ) . There were no differences between the 2 groups in secondary end points . Conclusions Ultrasound-guided serratus plane block spread in the craniocaudal direction is more widespread with 40 mL than with 20 mL of 0.375 % ropivacaine . The time until the first postoperative analgesic rescue dose was not extended by a larger volume of injection . Clinical Trials Registration UMIN Clinical Trials Registry ( identifier UMIN000016549 ) BACKGROUND Breast surgery is an exceedingly common procedure with an increased incidence of acute and chronic pain . Pectoral nerve block is a novel peripheral nerve block alternative to neuro-axial and paravertebral blocks for ambulatory breast surgeries . OBJECTIVES This study aims to compare the analgesic efficacy and safety of modified Pecs block with ketamine plus bupivacaine versus bupivacaine in patients undergoing breast cancer surgery . STUDY DESIGN A r and omized , double-blind , prospect i ve study . SETTING Academic medical center . METHODS This study is registered at www . clinical trials.gov under number : ( NCT02620371 ) after approval by the ethics committee of South Egypt Cancer Institute , Assuit University , Assuit , Egypt . Sixty patients aged 18 - 60 years scheduled for modified radical mastectomy were enrolled and r and omly assigned into 2 groups ( 30 patients each ) : Control group patients were given ultrasound-guided , Pecs block with 30 mL of 0.25 % bupivacaine only . Ketamine group patients were given ultrasound-guided , Pecs block with 30 mL of 0.25 % bupivacaine plus ketamine hydrochloride ( 1 mg/kg ) . Patients were followed up for 48 hours postoperatively for vital signs , VAS score , first request of rescue analgesia and total morphine consumption , sedation score , and side effects . RESULTS Ketamine plus bupivacaine in Pecs block compared to bupivacaine alone prolonged the mean time of first request of analgesia ( 18.25 ± 1.98 ) , ( 12.56 ± 2.64 ) , respectively ( P < 0.001 ) , reduced total morphine consumption ( 12.50 ± 4.63 ) , ( 18.86 ± 6.28 ) , respectively ( P = 0.016 ) . With no significant difference in hemodynamics , respiratory rate , oxygen saturation , VAS and sedation scores , and side effects observed between the 2 groups ( P > 0.05 ) . LIMITATIONS This study is limited by its sample size . CONCLUSION The addition of ketamine to modified Pecs block prolonged the time to first request of analgesia and reduced total opioid consumption without serious side effects in patients who underwent a modified radical mastectomy . KEY WORDS Ketamine , bupivacaine , pecs block , postoperative , pain , breast cancer Background and Objectives General anesthesia for breast surgery may be supplemented by using a regional anesthetic technique . We evaluated the efficacy of the first pectoral nerve block ( Pecs I \n Output:\n " }, { "from": "agent", "value": "Quantitative analysis suggests that dexamethasone and gabapentin reduced postoperative pain .\nThe use of paravertebral blocks also reduced postoperative pain scores , analgesia consumption and the incidence of postoperative nausea and vomiting .\nIntra-operative opioid requirements were documented to be lower when a pectoral nerves block was performed , which also reduced postoperative pain scores and opioid consumption ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: This paper reports the results of two studies of depressed patients , evaluating the efficacy and toleration of the selective serotonin reuptake inhibitor ( SSRI ) sertraline in a general practice setting in the UK . In the first of these studies , 308 patients , with a DSM-III-R diagnosis of major depressive episode , were treated for 6 weeks with either sertraline 50–100 mg/day or the tricyclic antidepressant dothiepin 75–150 mg/day , or placebo . Seventy-six per cent of sertraline-treated patients were maintained on the lower dose ( 50 mg/day ) , whereas 81 % of dothiepin-treated patients required the higher dose ( 150 mg/day ) . Sertraline-treated patients demonstrated a significant improvement in the Montgomery-Asberg Depression Rating Scale ( MADRS ) and the Clinical Global Impression ( CGI ) severity scores compared with placebo-treated patients , while dothiepin-treated patients did not show significant improvement compared with placebo . The active drugs were well tolerated , and there were no significant differences in adverse events between the groups . The second study , “ Sertraline in General Practice , A Multicenter Assessment ” , or SIGMA , was a large , multicentre trial with a cohort of 3396 patients recruited to receive 6 weeks of treatment . Patients started on sertraline 50 mg/day , and for 59 % of patients this was the final dose ; less than 10 % of patients reached final doses of more than 100 mg/day . A 50 % or greater reduction in MADRS scores was seen in 69 % of patients across a wide range of severity of symptoms at baseline , and 87 % of patients demonstrated excellent or good toleration of the drug . A review of the relevant literature and the results of these studies show that sertraline is well suited to treatment of depression in the general practice setting Mild depressive syndromes are highly prevalent among primary -care patients . Evidence -based treatment recommendations need to be derived directly from this diagnostically heterogeneous group . The primary aim was to assess the efficacy of sertraline and cognitive-behavioural group therapy for treatment of depressed primary -care patients , the secondary aim was to evaluate if receiving treatment according to free choice is associated with a better outcome than r and omization to a particular treatment . We conducted a r and omized , placebo-controlled , single-centre , 10-wk trial with five arms : sertraline ( flexible dosages up to 200 mg/d ) ( n = 83 ) ; placebo ( n = 83 ) ; manual-guided cognitive-behavioural group therapy ( one individual session and nine group sessions per 90 min ) ( n = 61 ) ; guided self-help group ( control condition , n = 59 ) ; and treatment with sertraline or cognitive-behavioural group therapy according to patients ' choice ( n = 82 ) . From 1099 consecutively screened adult patients , 368 formed the intent-to-treat population with milder forms of depression . Primary outcome was a global efficacy measure combining z-converted Hamilton Depression Rating Scale and clinician-rated Inventory for Depressive Symptomatology scores . Sertraline was superior to placebo ( p = 0.03 ) . Outcome for guided self-help groups was worse compared to cognitive-behavioural group therapy ( p = 0.002 ) and compared to all other treatment arms including pill placebo ( secondary analyses ) . Outcome in the patients ' choice arm was similar to that in the sertraline and cognitive-behavioural group therapy . Overall , sertraline is efficacious in primary -care patients with milder forms of depression . The superiority of cognitive-behavioural group therapy over guided self-help groups might partly be explained by ' nocebo ' effects of the latter Methods After initial screening and a seven-day washout period , in the case of patients who had received previous antidepressant medication , 47 adult patients who fulfiIled Feighner ’s criteria for the diagnosis of depression ( 1 ) and had a Hamilton Depression Rating Scale ( HAMD ) total score ( 21-item ) of 18 or more were r and omized to treatment with either paroxetine or placebo . The intended duration of double-blind treatment was four weeks . Paroxetine at a single daily dose of 30 mg or matched placebo was administered at night . No concomitant psychotropic medication other than triazolam or flunitrazepam as a hypnotic was permitted . Patients attended for review on days 7,14 , and 28 . The measures of severity of depression were the HAMD scale total score ( 21-item ) , the Beck Depression Inventory ( BDI ) , the Visual Analogue Scale ( VAS ) , and the Clinical Global Impression ( CGI ) of severity of illness . Assessment of tolerability was based on reports of adverse experiences , both spontaneously reported and elicited in response to asideeffect symptom checklist , physical examination , vital signs , and laboratory investigations A controlled double-blind trial of amitriptyline at two dosage levels ( 75 and 150 mg/day ) , amylobarbitone ( 150 mg/day ) , and an inert substance for a period of four weeks was conducted on four matched groups of women attending their general practitioners and suffering from a depressive illness . Improvement at 7 and 28 days was noted on several measures of depression and anxiety in all treatment groups . Of these treatments amitriptyline 150 mg/day was the most consistent in relieving depression and anxiety . Troublesome side effects were equally distributed among the four treatments In summary , the clinical results of this double-blind study clearly show that imipramine , as expected , demonstrated significant antidepressive properties in out patients suffering from major depressive disorders . In contrast , adinazolam showed rather mild and weak antidepressive properties , and in no measures did its response differ significantly from that of diazepam . These findings are quite in contrast to those obtained by the authors in an earlier study with alprazolam ( Rickels et al. , 1987 ) in which alprazolam and imipramine produced rather similar results and both were significantly better than placebo , while diazepam was not . While the rather high dropout rate may well be considered a limitation of the study , the dropout rate is equally distributed between all four treatments . And since both decreasing sample size and endpoint analyses which include all patients with at least one week data , provide rather similar results , the findings can be considered as robust despite the high dropout rate . While the authors consider those findings the most robust in which endpoint and completer analyses results are rather similar , when high dropout rates occur , endpoint analyses should be given more weight than completer analyses as they are more representative of actual clinical practice . The present findings therefore suggest that adinazolam clearly possesses less antidepressive properties than imipramine and not more than diazepam and these findings are in agreement with other studies which found lack of significant antidepressant activity for such benzodiazepines as diazepam ( Covi et al. , 1974 ) and chlordiazepoxide ( Lipman et al. , 1986 ) . The presence of only borderline antidepressive effects combined with rebound symptoms occurring already after only 6 weeks of therapy does not recommend adinazolam for use in depression . ( ABSTRACT TRUNCATED AT 250 WORDS Escitalopram , a selective serotonin reuptake inhibitor ( SSRI ) , was compared to placebo in a study of patients with major depressive disorder ( DSM-IV ) who had baseline Montgomery – Åsberg Depression Rating Scale ( MADRS ) total scores ≥22 and ≤40 . After a 1-week , single-blind placebo period , patients were r and omized to receive escitalopram 10 mg/day ( n = 191 ) or placebo ( n = 189 ) in an 8-week , double-blind period . The primary efficacy analysis of adjusted mean change in MADRS total score from baseline showed a statistically significantly larger effect for escitalopram than for placebo with a treatment difference at week 8 ( last observation carried forward , LOCF ) of 2.7 points ( SE 0.85;P = 0.002 ) . In further by-week efficacy analyses , the effect of escitalopram was consistently larger than that of placebo ( P < 0.05 ) beginning at week 1 ( Clinical Global Impression – Improvement score ) , week 2 ( MADRS score ) or week 3 ( Clinical Global Impression – Severity score ) . Escitalopram was very well tolerated with a low overall withdrawal rate similar to that for placebo . Nausea was the only adverse event reported significantly more in escitalopram-treated patients than in placebo-treated patients , although it was infrequent and transient . Escitalopram 10 mg/day had a statistically significantly better antidepressant effect than placebo as early as week 1 , and was safe and very well tolerated AIMS This paper describes the methods used in a study of the prevalence and types of common mental disorders among patients attending New Zeal and general practice s , and reports some key findings from the first phase of the study . The study also aim ed to determine the degree of associated disability and other factors influencing recognition , management , course and outcome of these disorders , and subsequent papers will address these issues . METHODS General practitioners ( GPs ) were selected r and omly . In the first phase of the study , all adult attenders at each practice on selected days were administered a short question naire , the General Health Question naire ( GHQ-12 ) , which screens for psychological symptoms . The GP recorded the reasons for each consultation , and was interviewed at the end of each day about selected patients to determine their opinion about the type of psychological problems experienced . Selected patients were then visited in their own homes and an extensive interview conducted , which included the Composite International Diagnostic Interview ( CIDI ) to determine mental health status , the World Health Organization 's Disability Assessment Schedule ( WHODAS ) to determine disability , and a detailed exploration of use of health services . In the second phase of the study , patients were contacted by telephone at three , six , nine and 12 months , and both patients and GPs were re-interviewed at 12 months . RESULTS The study achieved a very high response rate among the GPs ( 90 % ) . Nearly all eligible patients ( 93 % ) completed the GHQ screening , and their response rate was 70 % for the first-phase interview . GPs thought that 54 % of female and 46 % of male patients had experienced some level of psychological problems in the past year . GHQ screening also found that more than half of those attending their general practitioner experienced some psychological symptoms at initial screening , and the CIDI interview found that more than one in three had a diagnosable mental disorder during the past 12 months . The most common mental disorders were depressive , anxiety and substance use disorders . These disorders were more common among younger than older general practice attenders , and comorbidity was high . CONCLUSIONS Mental health problems are very common among general practice attenders . Contrary to the prevailing view that general practitioners seldom identify psychological problems in their patients , they identified about half their patients as having some type of psychological problems in the past year , although they considered that these were moderate or severe in about only one in ten patients . Further work from this large New Zeal and study will focus on the nature of the relationship between disorder and disability , and on the recognition , management and outcome of psychological problems One hundred and fifteen patients from 5 general practice s participated in a 12-week , double-blind study comparing L-tryptophan , amitriptyline , L-tryptophan-amitriptyline combination and placebo in the treatment of depression . Analysis of total score on the Hamilton Depression Scale and a global rating of depression showed that all 3 active treatments were more effective than placebo . Significantly more patients were withdrawn as treatment failures in the placebo group compared with the active treatment groups . Side-effects necessitated withdrawal of more patients from the amitriptyline group than from the other active treatment groups , but this difference was not significant . Plasma amitriptyline and nortriptyline levels were similar in the amitriptyline and combined treatment groups . St and ard haematological and biochemical profiles did not alter significantly in any group , but mean heart rate was significantly increased in patients receiving amitriptyline . There was no change in free or total plasma tryptophan concentration with treatment or on remission of symptoms In a multicenter , placebo-controlled , clinical trial , the efficacy of Limbitrol was compared with that of its components , amitriptyline and chlordiazepoxide . All patients had a diagnosis of primary depression . Data from 279 patients were evaluated using the Hamilton depression scale , the Beck depression inventory , and physician and patient global change measures .Statistically significant differences favoring Limbitrol occurred after 1 week of treatment , and a trend in favor of Limbitrol continued throughout the remaining 3 weeks . In most efficacy comparisons , the combination was as good as , or better than , amitriptyline alone . It was superior to chlordiazepoxide alone after 2 and 4 weeks of treatment . Each component produced an independent contribution to the total therapeutic effect : the chlordiazepoxide effect was more prominent in the first 2 weeks and the amitriptyline effect in the latter 2 weeks . A trend favoring amitriptyline over chlordiazepoxide was evident by week 4.The overall incidence of side effects was comparable in both Limbitrol- and amitriptyline-treated groups . Limbitrol-treated patients exhibited more sedation , but significantly fewer Limbitrol patients discontinued treatment prematurely because of side effects Of 580 patients r and omly assigned to short-term , double- \n Output:\n " }, { "from": "agent", "value": "AUTHORS ' CONCLUSIONS Both TCAs and SSRIs are effective for depression treated in primary care" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: 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 Total sagittal knee laxity and postural control in the sagittal and frontal planes were measured in 25 patients at a mean of 36 months ( range , 27 to 44 ) after anterior cruciate ligament reconstruction and in a control group consisting of 20 uninjured age- and activity-matched subjects . Body sway was measured in the sagittal plane on a stable and on a sway-referenced force plate in single-legged stance , double-legged stance , or both , with the eyes open and closed . Postural reactions to perturbations in the sagittal and frontal planes were recorded in the single-legged stance with the eyes open . Total sagittal plane laxity was significantly greater in the anterior cruciate ligament-reconstructed knee ( 11.2 mm ; range , 6 to 15 ) than in the uninjured knee ( 8.9 mm ; range , 6 to 12 ) or in the control group ( 6.0 mm ; range , 5 to 8) . In spite of this , the patients , in comparison with the controls , exhibited normal postural control except in two variables — the reaction time and the latency between the start of force movement to maximal sway in the sagittal plane perturbations . This supports the hypothesis that rehabilitation , with proprioceptive and agility training , is an important component in restoring the functional stability in the anterior cruciate ligament-reconstructed knee The correlation between the prospect i ve course of proprioceptive improvement and knee stability after anterior cruciate ligament reconstruction was investigated in 38 patients . Proprioception , on the basis of the patient ’s capacity to reposition the limb accurately , was evaluated at 3-month intervals for 24 months after hamstring graft anterior cruciate ligament surgery . Knee stability was evaluated concurrently with a KT-2000 knee arthrometer . Thirty patients experienced improvement in postoperative position sense in at least one of the examinations , although eight patients had no improvement at any time . Of the 30 patients who had improvement , 28 maintained improved position sense from 18 months to the final followup . Thirty patients maintained significantly better knee stability for a postoperative period of at least 24 months . These results indicated that a minimum of 18 months after anterior cruciate ligament reconstruction may be needed for complete restoration of the proprioceptive function in knees , although the mean position sense in all patients gradually improved from 9 months . Improvement in postoperative knee stability may have facilitated recovery of proprioception The efficacy of two non-operative rehabilitation programs was studied in a consecutive r and omized controlled clinical trial of 100 patients after 12 months subsequent to an acute anterior cruciate ligament ( ACL ) injury . Follow up of r and omization to two training models was evaluated after 3 and 12 months : A self-monitored training program ( SM ) of traditional mobility and muscle strength training of the injured leg was compared to a supervised ( SV ) training model exercising postural function in closed kinetic-chains . Nearly 50 % of the patients in the SM group required supervision after 6 weeks . An intention-to-treat analysis was performed and showed significantly better values in most of the results of the supervised group at 3 and 12 months . An alternative analysis of subgroups showed a significant difference between transferred male patients and original SV male patients at 3 months but not at 12 months , indicating the importance of initial guiding after an ACL injury . No such difference was observed in the female patients \n Output:\n " }, { "from": "agent", "value": "Insufficient evidence was found to support the efficacy of one exercise intervention over another .\nThis review has demonstrated an absence of evidence to support one form of exercise intervention against another and the use of supplementary exercises in the management of isolated ACL injuries ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Objectives : To investigate the effectiveness of screening for liver cancer in reducing mortality from the disease in a high-risk population in China . Setting : A r and omised controlled trial was carried out among men aged 30 - 69 who were chronic carriers of hepatitis-B virus ( HBsAg positive ) during the period 1989 - 1995 in Qidong county , Jiangsu Province , China . Methods : 5581 HBsAg carriers were identified by population screening and r and omly assigned to a screening group ( group A , 3712 men ) , and controls ( group B , 1869 men ) . Screening was planned to be six monthly alpha-fetoprotein ( AFP ) assays , with follow-up of subjects having an abnormal ( ≥20 μg/l ) test . All subjects were followed up for liver cancer and /or death until 31 December 1995 . Results : The overall sensitivity and specificity of the programme was 55.3 % and 86.5 % , respectively ; in subjects who complied with all scheduled screening tests , the values were 80.0 % and 80.9 % . Three hundred and seventy-four primary liver cancer ( PLC ) cases were diagnosed . The percentage of cases in stage I was significantly higher in group A ( 29.6 % ) than in group B ( 6.0 % ) . The one- , three- , and five-year relative survival rates were 23.7 % , 7.0 % , and 4.0 % in group A , and 9.7 % , 4.0 % , and 4.1 % in group B respectively , with no difference in five-year survival between the groups . The mortality rate in the screened group ( 1138 per 100,000 person-years ) was not significantly different from that in the controls ( 1114 per 100,000 ) . A Poisson regression model showed that the probability of death ( rate ratio ) in the screening group was 0.83 ( 95 % CI 0.68 - 1.03 ) relative to the control group . Conclusions : Screening with AFP result ed in earlier diagnosis of liver cancer , but the gain in lead time did not result in any overall reduction in mortality , because therapy for the patients found by screening was ineffective . Further studies using improved methods of screening , diagnosis and treatment are indicated BACKGROUND The European R and omized Study of Screening for Prostate Cancer was initiated in the early 1990s to evaluate the effect of screening with prostate-specific-antigen ( PSA ) testing on death rates from prostate cancer . METHODS We identified 182,000 men between the ages of 50 and 74 years through registries in seven European countries for inclusion in our study . The men were r and omly assigned to a group that was offered PSA screening at an average of once every 4 years or to a control group that did not receive such screening . The predefined core age group for this study included 162,243 men between the ages of 55 and 69 years . The primary outcome was the rate of death from prostate cancer . Mortality follow-up was identical for the two study groups and ended on December 31 , 2006 . RESULTS In the screening group , 82 % of men accepted at least one offer of screening . During a median follow-up of 9 years , the cumulative incidence of prostate cancer was 8.2 % in the screening group and 4.8 % in the control group . The rate ratio for death from prostate cancer in the screening group , as compared with the control group , was 0.80 ( 95 % confidence interval [ CI ] , 0.65 to 0.98 ; adjusted P=0.04 ) . The absolute risk difference was 0.71 death per 1000 men . This means that 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer . The analysis of men who were actually screened during the first round ( excluding subjects with noncompliance ) provided a rate ratio for death from prostate cancer of 0.73 ( 95 % CI , 0.56 to 0.90 ) . CONCLUSIONS PSA-based screening reduced the rate of death from prostate cancer by 20 % but was associated with a high risk of overdiagnosis . ( Current Controlled Trials number , IS RCT N49127736 . BACKGROUND The effect of screening with prostate-specific-antigen ( PSA ) testing and digital rectal examination on the rate of death from prostate cancer is unknown . This is the first report from the Prostate , Lung , Colorectal , and Ovarian ( PLCO ) Cancer Screening Trial on prostate-cancer mortality . METHODS From 1993 through 2001 , we r and omly assigned 76,693 men at 10 U.S. study centers to receive either annual screening ( 38,343 subjects ) or usual care as the control ( 38,350 subjects ) . Men in the screening group were offered annual PSA testing for 6 years and digital rectal examination for 4 years . The subjects and health care providers received the results and decided on the type of follow-up evaluation . Usual care sometimes included screening , as some organizations have recommended . The numbers of all cancers and deaths and causes of death were ascertained . RESULTS In the screening group , rates of compliance were 85 % for PSA testing and 86 % for digital rectal examination . Rates of screening in the control group increased from 40 % in the first year to 52 % in the sixth year for PSA testing and ranged from 41 to 46 % for digital rectal examination . After 7 years of follow-up , the incidence of prostate cancer per 10,000 person-years was 116 ( 2820 cancers ) in the screening group and 95 ( 2322 cancers ) in the control group ( rate ratio , 1.22 ; 95 % confidence interval [ CI ] , 1.16 to 1.29 ) . The incidence of death per 10,000 person-years was 2.0 ( 50 deaths ) in the screening group and 1.7 ( 44 deaths ) in the control group ( rate ratio , 1.13 ; 95 % CI , 0.75 to 1.70 ) . The data at 10 years were 67 % complete and consistent with these overall findings . CONCLUSIONS After 7 to 10 years of follow-up , the rate of death from prostate cancer was very low and did not differ significantly between the two study groups . ( Clinical Trials.gov number , NCT00002540 . PURPOSE This clinical trial is aim ed at evaluating the impact of prostate cancer screening on cancer-specific mortality . SUBJECTS AND METHODS Forty-six thous and four hundred and eighty-six ( 46,486 ) men aged 45 - 80 years registered in the electoral roll of the Quebec city area were r and omized in 1988 between screening and no screening . Screening included measurement of serum prostatic specific antigen ( PSA ) using 3.0 ng/ml as upper limit of normal and digital rectal examination ( DRE ) at first visit . At follow-up visits , serum PSA only was used . RESULTS Seventy-four ( 74 ) deaths from prostate cancer occurred in the 14,231 unscreened controls while 10 deaths were observed in the screened group of 7,348 men during the first 11 years following r and omization . Median follow-up of screened men was 7.93 years . A Cox proportional hazards model of the age at death from prostate cancer shows a 62 % reduction ( P < 0.002 , Fisher 's exact test ) of cause-specific mortality in the screened men ( P = 0.005 ) . These results are in agreement with the continuous decrease of prostate cancer mortality observed in North America Purpose Screening for hepatocellular carcinoma ( HCC ) has been conducted for over 20 years , but there is no conclusive evidence that screening may reduce HCC mortality . The aim of this study was to assess the effect of screening on HCC mortality in people at increased risk . Methods This study included 18,816 people , aged 35–59 years with hepatitis B virus infection or a history of chronic hepatitis in urban Shanghai , China . Participants were r and omly allocated to a screening ( 9,373 ) or control ( 9,443 ) group . Controls received no screening and continued to use health-care facilities . Screening group participants were invited to have an AFP test and ultrasonography examination every 6 months . Screening was stopped in December 1997 ; by that time screening group participants had been offered five to ten times . All participants were followed up until December 1998 . The primary outcome measure was HCC mortality . Results The screened group completed 58.2 percent of the screening offered . When the screening group was compared to the control group , the number of HCC was 86 versus 67 ; sub clinical HCC being 52 ( 60.5 % ) versus 0 ; small HCC 39 ( 45.3 % ) versus 0 ; resection achieved 40 ( 46.5 % ) versus 5 ( 7.5 % ) ; 1- , 3,- , and 5-year survival rate 65.9 % , 52.6 % , 46.4 % versus 31.2 % , 7.2 % , 0 , respectively . Thirty-two people died from HCC in the screened group versus 54 in the control group , and the HCC mortality rate was significantly lower in the screened group than in controls , being 83.2/100,000 and 131.5/100,000 , respectively , with a mortality rate ratio of 0.63 ( 95%CI 0.41–0.98 ) . Conclusions Our finding indicated that biannual screening reduced HCC mortality by 37 % Stored sample s from women in the Stockholm screening study were reassayed for CA125II ( Centocor , Malvern , PA ) and OVX1 . The postmenopausal women older than age 50 without ovarian cancer were r and omly split into a training set to develop a screening test based on longitudinal marker levels and a second set to vali date the test . The CA125II data from each woman is summarized by the slope and intercept from a linear regression of log(CAl25II ) on time since first sample . The slope versus the intercept for the training set and the ovarian cancer cases formed a bivariate scatter plot . A curve was drawn on the scatter plot that separated most of the women with ovarian cancer from all other women ; it delineated a screening test . The specificity of this test was examined on the validation set with a specificity of 99.8 % . Bayes ' theorem was used to calculate the risk of ovarian cancer ( ROC ) based on the intercept , slope , and assay variability . It is important to account for assay variability because it can produce large slopes over short periods of time . The maximum risk , which identified 83 % ( 5 of 6 ) of the ovarian cancers detected within a year of last assay , was applied as a test to the training set and confirmed a high specificity of 99.7 % . With this specificity and sensitivity , the ROC algorithm using the CA125II assay has an estimated positive predictive value of 16 % , substantially greater than the positive predictive value based on a single assay . Further study is planned to confirm the sensitivity of this approach . Cancer 1995 ; 76:2004‐10 New stool tests may be promising tools for future colorectal cancer ( CRC ) screening . The aim of this review was to summarize current evidence of performance characteristics and practicalness in a population ‐based screening setting of recently developed stool tests . The MEDLINE data base was search ed for relevant articles published until July 2004 . Studies were included if they comprised more than 10 cases and more than 10 controls . Details on study population , performance characteristics and stool collection procedure were taken into account . Overall , 29 studies , mostly retrospective , were included , investigating 17 different stool markers or marker combinations . Underlying study population s were very heterogeneous and mostly very small . Half of the studies reported sensitivity for adenomas in addition to sensitivity for CRC , and fewer than half reported sensitivity by tumor stage or location . Performance characteristics of stool tests varied to a large extent . For most DNA‐based markers , specificity was about 95 % or higher , but sensitivity was mostly low even for invasive CRC . More studies with larger sample sizes were done for protein‐based markers , which typically had lower specificity . In most studies , stool sample s were frozen within a rather short time period after defecation . While promising performance characteristics have been reported for some tests , more pervasive evidence from larger , prospect ively design ed studies , which also consider aspects of practicalness , e.g. , the possibility of mailing the sample s , is needed . © 2005 Wiley‐Liss , PURPOSE To evaluate prevalence screening in the first prospect i ve trial of a new ovarian cancer screening ( OCS ) strategy ( risk of ovarian cancer or ROC algorithm ) on the basis of age and CA125 profile . PATIENTS AND METHODS Postmenopausal women , > or = 50 years were r and omly assigned to a control group or screen group . Screening involved serum CA125 , interpreted using the ROC algorithm . Participants with normal results returned to annual screening ; those with intermediate results had repeat CA125 testing ; and those with elevated values underwent transvaginal ultrasound ( TVS ) . Women with abnormal or persistently equivocal TVS were referred for a gynecologic opinion . RESULTS Thirteen thous and five hundred eighty-two women were recruited . Of 6,682 women r and omly assigned to screening , 6, \n Output:\n " }, { "from": "agent", "value": "Of these markers , only the use of FOBT in screening for CRC has been shown to reduce mortality from cancer .\nThis lack of sensitivity and specificity when combined with the low prevalence of cancers in the general population means that most biomarkers , if used alone , have a low positive predictive value in screening asymptomatic population s. Indeed , it is the low prevalence of cancer in the general population that prohibits most biomarkers from being used alone , in screening for cancer ( 4,5 ) ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: OBJECTIVES The objective of this study was to characterize the bleeding , transfusion , and other outcomes of patients related to the timing of prasugrel or clopidogrel withdrawal before coronary artery bypass grafting ( CABG ) . BACKGROUND There is little evidence to guide clinical decision making regarding the use of prasugrel in patients who may need urgent or emergency CABG . Experience with performing CABG in the presence of clopidogrel has raised concern about perioperative bleeding complications that are unresolved . METHODS A subset of the TRITON-TIMI 38 study ( Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis In Myocardial Infa rct ion 38 ) , in which patients with acute coronary syndrome were r and omized to treatment with aspirin and either clopidogrel or prasugrel , underwent isolated CABG ( N = 346 ) . A supplemental case report form was design ed and administered , and the data combined with the existing TRITON-TIMI 38 data base . Baseline imbalances were corrected for using elements of the European System for Cardiac Operative Risk Evaluation and The Society of Thoracic Surgeons predictive algorithm . RESULTS A significantly higher mean 12-h chest tube blood loss ( 655 ± 580 ml vs. 503 ± 378 ml ; p = 0.050 ) was observed with prasugrel compared with clopidogrel , without significant differences in red blood cell transfusion ( 2.1 U vs. 1.7 U ; p = 0.442 ) or the total donor exposure ( 4.4 U vs. 3.0 U ; p = 0.463 ) . All-cause mortality was significantly reduced with prasugrel ( 2.31 % ) compared with 8.67 % with clopidogrel ( adjusted odds ratio : 0.26 ; p = 0.025 ) . CONCLUSIONS Despite an increase in observed bleeding , platelet transfusion , and surgical re-exploration for bleeding , prasugrel was associated with a lower rate of death after CABG compared with clopidogrel INTRODUCTION The antiplatelet effect of st and ard or increased clopidogrel doses in patients with ST- segment elevation acute myocardial infa rct ion ( STEMI ) has never been studied . In this study we compared the antiplatelet effect of a 75 mg daily maintenance dose of clopidogrel with 150 mg in patients with STEMI undergoing primary percutaneous coronary intervention ( PCI ) . MATERIAL S AND METHODS Fifty-four patients with STEMI undergoing PCI were r and omly allocated to receive either 75 mg/day clopidogrel ( group 1 ) or 150 mg/day ( group 2 ) for 1 month . Platelet function , measured by 5 different assays , was determined at 3 time points : 38+/-8 hours after the procedure , 1 week and 1 month after r and omization . RESULTS In group 1 , mean + /- SD platelet reactivity index ( PRI ) measured with the VASP assay was 57.7+/-15.7 % and 46.9+/-15.7 % at 1 week and 1 month , respectively , compared to 38.8+/-15.7 % and 34.9+/-12.6 % in group 2 ( p=0.0001 ) . Same results were observed for light transmittance aggregometry , whole blood aggregometry and VerifyNow , but not for thromboelastometry . In contrast to what may be expected , the 75 mg daily maintenance dose took longer than 1-week to provide the full clopidogrel antiplatelet effect . Furthermore , patients in group 2 had a nearly 50 % reduction in C-reactive protein levels both at 1 week and 1 month . CONCLUSION In patients with STEMI and poor responsiveness to clopidogrel a 150 mg daily maintenance dose of clopidogrel is associated with a significant reduction of platelet aggregation and a trend towards reduced inflammation The r and omized TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infa rct ion ( TRITON-TIMI ) 38 trial compared prasugrel and clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention ( PCI ) . Patients treated with prasugrel had fewer ischemic events but more procedure-related bleeding . In the present study , we aim ed to determine the effect of bivalirudin on bleeding in patients treated with prasugrel . A total of 692 patients with consecutive acute coronary syndrome underwent PCI with stent implantation and were anticoagulated with bivalirudin . The patients were divided into 2 groups according to the antiplatelet regimen ( clopidogrel or prasugrel ) chosen during or just after PCI . The bleeding complications during hospitalization were tabulated . Ischemic events were analyzed during hospitalization and at 30 days . Prasugrel was used in 96 patients ( 13.9 % ) and clopidogrel in 596 ( 86.1 % ) . The clinical and procedural characteristics were similar , although the clopidogrel patients more often reported systemic hypertension ( p = 0.01 ) , previous PCI ( p < 0.001 ) , and chronic renal insufficiency ( p = 0.05 ) . During hospitalization , the bleeding and ischemic complication rates were similar and low in both groups ( major in-hospital complications 4.2 % for clopidogrel vs 2.1 % for prasugrel , p = 0.6 ; Thrombolysis In Myocardial Infa rct ion major bleeding 2.5 % vs 2.1 % , p = 1.00 ; Thrombolysis In Myocardial Infa rct ion minor bleeding 4.2 % vs 5.2 % , p = 0.6 ) . At 30 days , no differences were found in ischemic events between both groups ( target vessel revascularization/major adverse cardiac events 5.4 % vs 2.1 % , p = 0.2 ) . In conclusion , prasugrel , when given after bivalirudin as the intraprocedural antithrombin agent for patients with acute coronary syndrome undergoing PCI , is as safe and effective as clopidogrel Background Although unstable coronary artery disease is the most common reason for admission to a coronary care unit , the long-term prognosis of patients with this diagnosis is unknown . This is particularly true for patients with diabetes mellitus , who are known to have a high morbidity and mortality after an acute myocardial infa rct ion . Methods and Results Prospect ively collected data from 6 different countries in the Organization to Assess Strategies for Ischemic Syndromes ( OASIS ) registry were analyzed to determine the 2-year prognosis of diabetic and nondiabetic patients who were hospitalized with unstable angina or non – Q-wave myocardial infa rct ion . Overall , 1718 of 8013 registry patients ( 21 % ) had diabetes . Diabetic patients had a higher rate of coronary bypass surgery than nondiabetic patients ( 23 % versus 20 % , P < 0.001 ) but had similar rates of catheterization and angioplasty . Diabetes independently predicted mortality ( relative risk [ RR ] , 1.57 ; 95 % CI , 1.38 to 1.81;P < 0.001 ) , as well as cardiovascular death , new myocardial infa rct ion , stroke , and new congestive heart failure . Moreover , compared with their nondiabetic counterparts , women had a significantly higher risk than men ( RR , 1.98 ; 95 % CI , 1.60 to 2.44 ; and RR , 1.28 ; 95 % CI , 1.06 to 1.56 , respectively ) . Interestingly , diabetic patients without prior cardiovascular disease had the same event rates for all outcomes as nondiabetic patients with previous vascular disease . Conclusions Hospitalization for unstable angina or non – Q-wave myocardial infa rct ion predicts a high 2-year morbidity and mortality ; this is especially evident for patients with diabetes . Diabetic patients with no previous cardiovascular disease have the same long-term morbidity and mortality as nondiabetic patients with established cardiovascular disease after hospitalization for unstable coronary artery disease In acute coronary syndromes ( ACS ) , a dual antiplatelet regimen with an adenosine diphosphate ( ADP ) receptor antagonist plus aspirin has become the cornerstone of treatment . The third-generation thienopyridine prasugrel and the cyclopentyl-triazolo-pyrimidine ticagrelor provide a greater , more rapid and consistent platelet inhibition compared to their predecessor clopidogrel . Based on their advantages over clopidogrel in two l and mark studies , both drugs received a class I recommendation for their use in ACS patients with and without ST segment elevation . Due to differences in ACS population s and conditions investigated , the relative merits of ticagrelor versus prasugrel in the treatment of ACS patients with planned invasive strategy can not be reliably estimated from independent trials . To date , no direct head-to-head comparison of ticagrelor and prasugrel in terms of clinical outcome exists . The aim of this multicenter , r and omized , open-label trial is to assess whether ticagrelor is superior to prasugrel in ACS patients with planned invasive strategy Background —Ticagrelor and prasugrel provide stronger platelet inhibition compared with clopidogrel . Direct pharmacodynamic comparison between them has not yet been reported in ST-segment – elevation myocardial infa rct ion patients . Methods and Results —In a prospect i ve , single-center , single-blind study , 55 out of 117 ( 47 % ) screened consecutive ST-segment – elevation myocardial infa rct ion patients undergoing primary percutaneous coronary intervention were r and omized to either ticagrelor 180 mg loading followed by 90 mg bid , or prasugrel 60 mg loading followed by 10 mg od for 5 days . Platelet reactivity ( PR ) was assessed with the VerifyNow P2Y12 function assay and the Multiplate Analyzer at 0 , 1 , 2 , 6 , 24 hours , and 5 days postr and omization . The primary end point , PR with VerifyNow at hour 1 , did not differ significantly between patients r and omized to ticagrelor versus prasugrel ( 257.3 P2Y12 reaction unit [ PRU ] , 95 % CI 230.8–283.8 versus 231.3 PRU , 95 % CI 205.3–257.4 ; P=0.2 ) . PR did not differ at 2 , 6 , and 24 hours , although at day 5 it was lower with ticagrelor than prasugrel ( 25.6 PRU , 95 % CI 12.3–38.9 versus 50.3 PRU , 95 % CI 36.4–64.1 ; P=0.01 ) . At hour 2 , high on-treatment PR rates ( cutoff 208 PRU ) were 46.2 % and 34.6 % for ticagrelor and prasugrel , respectively , decreased significantly thereafter , whereas did not differ significantly between the 2 agents at all the time points of the study . Conclusions —In patients with ST-segment – elevation myocardial infa rct ion undergoing primary percutaneous coronary intervention , both ticagrelor and prasugrel exhibit an initial delay in the onset of their antiplatelet action . Ticagrelor did not appear superior to prasugrel in reducing PR during the first 24 hours of ST-segment – elevation myocardial infa rct ion . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT01463163 BACKGROUND Recurrent ischemic events occurred even during routine use of 75 mg clopidogrel in addition to aspirin , that indicated a potentially insufficient maintenance dosage of clopidogrel . The aim of the present study was to evaluate the short-term efficacy and safety of a 150 mg maintenance dose of clopidogrel following a 600 mg loading dose in patients with an acute coronary syndrome ( ACS ) undergoing drug eluting stent ( DES ) implantation . METHODS Between November 2005 and November 2006 , a total of 813 consecutive ACS patients undergoing DES implantation were enrolled . A 600 mg loading dose was administered before percutaneous coronary intervention ( PCI ) and patients were r and omized to receive clopidogrel 75 mg or 150 mg for 30 days in addition to 300 mg aspirin daily . Primary end points were the composite of cardiac death , non-fatal myocardial infa rct ion ( MI ) and urgent target vessel revascularization ( UTVR ) . Secondary end points included stent thrombosis ( ST ) , major and minor bleeding events at 30 days . RESULTS At a follow-up period of 30 days , 4 ( 1.0 % ) patients in the 150 mg group and 9 ( 2.2 % ) patients in the 7 \n Output:\n " }, { "from": "agent", "value": "A key strength of the review is that it demonstrates the cost-effectiveness of prasugrel compared with clopidogrel using the generic price of clopidogrel .\nAlthough the report demonstrates the cost-effectiveness of prasugrel compared with clopidogrel at a threshold of £ 20,000 to £ 30,000 per QALY gained , the long-term modelling is vulnerable to major assumptions regarding long-term gains ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: Background To assess the feasibility and early toxicity of selective , IMRT-based dose escalation ( simultaneous integrated boost ) to biopsy proven dominant intra-prostatic lesions visible on MRI . Methods Patients with localized prostate cancer and an abnormality within the prostate on endorectal coil MRI were eligible . All patients underwent a MRI-guided transrectal biopsy at the location of the MRI abnormality . Gold fiducial markers were also placed . Several days later patients underwent another MRI scan for fusion with the treatment planning CT scan . This fused MRI scan was used to delineate the region of the biopsy proven intra-prostatic lesion . A 3 mm expansion was performed on the intra-prostatic lesions , defined as a separate volume within the prostate . The lesion + 3 mm and the remainder of the prostate + 7 mm received 94.5/75.6 Gray ( Gy ) respectively in 42 fractions . Daily seed position was verified to be within 3 mm . Results Three patients were treated . Follow-up was 18 , 6 , and 3 months respectively . Two patients had a single intra-prostatic lesion . One patient had 2 intra-prostatic lesions . All four intra-prostatic lesions , with margin , were successfully targeted and treated to 94.5 Gy . Two patients experienced acute RTOG grade 2 genitourinary ( GU ) toxicity . One had grade 1 gastrointestinal ( GI ) toxicity . All symptoms completely resolved by 3 months . One patient had no acute toxicity . Conclusion These early results demonstrate the feasibility of using IMRT for simultaneous integrated boost to biopsy proven dominant intra-prostatic lesions visible on MRI . The treatment was well tolerated PURPOSE To prospect ively determine the accuracies of T2-weighted magnetic resonance ( MR ) imaging , dynamic contrast material -enhanced MR imaging , and quantitative three-dimensional ( 3D ) proton MR spectroscopic imaging of the entire prostate for prostate cancer localization , with whole-mount histopathologic section findings as the reference st and ard . MATERIAL S AND METHODS This study was approved by the institutional review board , and informed consent was obtained from all patients . Thirty-four consecutive men with a mean age of 60 years and a mean prostate-specific antigen level of 8 ng/mL were examined . The median biopsy Gleason score was 6 . T2-weighted MR imaging , dynamic contrast-enhanced MR imaging , and 3D MR spectroscopic imaging were performed , and on the basis of the image data , two readers with different levels of experience recorded the location of the suspicious peripheral zone and central gl and tumor nodules on each of 14 st and ardized regions of interest ( ROIs ) in the prostate . The degree of diagnostic confidence for each ROI was recorded on a five-point scale . Localization accuracy and ROI-based receiver operating characteristic ( ROC ) curves were calculated . RESULTS For both readers , areas under the ROC curve for T2-weighted MR , dynamic contrast-enhanced MR , and 3D MR spectroscopic imaging were 0.68 , 0.91 , and 0.80 , respectively . Reader accuracy in tumor localization with dynamic contrast-enhanced imaging was significantly better than that with quantitative spectroscopic imaging ( P < .01 ) . Reader accuracy in tumor localization with both dynamic contrast-enhanced imaging and spectroscopic imaging was significantly better than that with T2-weighted imaging ( P < .01 ) . CONCLUSION Compared with use of T2-weighted MR imaging , use of dynamic contrast-enhanced MR imaging and 3D MR spectroscopic imaging facilitated significantly improved accuracy in prostate cancer localization The study was approved by the animal care and use committee . The purpose of the study was to prospect ively establish proof of principle in vivo in canines for a magnetic resonance ( MR ) imaging-compatible robotic system design ed for image-guided prostatic needle intervention . The entire robot is built with nonmagnetic and dielectric material s and in its current configuration is design ed to perform fully automated brachytherapy seed placement within a closed MR imager . With a 3.0-T imager , in four dogs the median error for MR imaging-guided needle positioning and seed positioning was 2.02 mm ( range , 0.86 - 3.18 mm ) and 2.50 mm ( range , 1.45 - 10.54 mm ) , respectively . The robotic system is capable of accurate MR imaging-guided prostatic needle intervention within a st and ard MR imager in vivo in a canine model OBJECTIVE The aim of this study was to assess the roles of transrectal color Doppler and gray-scale sonography in revealing prostatic cancer , using biopsy as the reference st and ard . SUBJECTS AND METHODS Two hundred fifty-six patients referred for urologic studies underwent transrectal sonography using gray-scale and color Doppler scanning . All abnormal areas shown on gray-scale or color Doppler sonography or both were targeted and biopsies were performed . The patients also underwent r and om sextant biopsies . All biopsies were individually correlated with histopathologic findings and all results were analyzed . RESULTS Cancer was found on biopsy in 100 patients ( 39 % ) , and equivocal sonographic results or prostatic intraepithelial neoplasia was found in 22 other patients ( 9 % ) . In 16 of the patients in whom cancer was detected , the tumors were correctly revealed only with color Doppler sonography . These 16 patients had a mean Gleason score of 6.4 ( range , 5 - 8 ) . Biopsy findings in these 16 patients showed eight patients with extensive lesions , three with moderate lesions , and five with minimal lesions . However , in nine other patients with cancer ( 9 % of cancers detected ) , both gray-scale and color Doppler sonography failed to reveal lesions that were found on sextant biopsy . An analysis showed that , although highly sensitive , color Doppler sonography was somewhat less specific than gray-scale sonography . CONCLUSION Color Doppler sonography should become a routine part of transrectal sonography of the prostate gl and to improve detection and targeting of lesions . The practice of performing r and om sextant biopsies should also continue OBJECTIVES The aim of this prospect i ve study was to evaluate the sensitivity of the sextant biopsy protocol compared with a more extensive procedure for the detection of prostate cancer and to define a biopsy model with the minimal number of biopsies necessary to maintain diagnostic accuracy . METHODS A total of 512 consecutive patients with suspected prostate cancer were examined with transrectal ultrasound ( TRUS ) and underwent TRUS-guided core biopsy . All patients had 8 or 10 st and ardized biopsy sample s taken , with the number depending on the size of the gl and . Additional biopsy sample s were taken from hypoechoic or hyperechoic lesions located outside the predetermined location for the st and ardized biopsies ( ie , target biopsies ) . The sensitivity of the detection of cancer for different combinations of biopsy sample s was analyzed and compared with that of our model with 8 to 10 biopsies . RESULTS In all , 276 cancers were detected , of which 88 ( 32 % ) had an isoechoic appearance . Sensitivity was 59 % for focal lesions detected by TRUS , 85 % to 97 % for different combinations of systematic biopsy sample s , and 93 % to 98 % for a combination of systematic and target biopsy sample s. The sensitivity for the st and ard sextant protocol was 85 % . By adding target biopsies , the sensitivity increased to 93 % . CONCLUSIONS The st and ard sextant protocol leaves 15 % of cancers undetected compared with results obtained from a more extensive biopsy procedure . By combining systematic and target sampling , the sensitivity increases ; however , a major concern is that the clinical importance of cancers detected by multiple biopsies needs to be evaluated The diagnosis of prostatic carcinoma is most commonly made today by transrectal ultrasound guided needle biopsy . Often hypoechoic and peripheral zone lesions are the only areas sample d. Recently , we showed that this approach missed a quarter of the cancers that would be detected by a systematic biopsy technique . We term these missed cancers isoechoic carcinomas . We review ed 1,549 systematic sextant prostate needle biopsies , of which 417 cancers were detected and subdivided into hypoechoic cancers ( cancers detected on biopsy of a hypoechoic sector and isoechoic cancers ( cancers found only in normal [ isoechoic ] peripheral zone ) . We noted in men with only isoechoic cancers that fewer biopsy cores per prostate revealed cancer ( mean 1.6 versus 3.0 , p < 0.0001 ) and that these men had lower serum prostate specific antigen levels ( mean 14.4 versus 43.7 , p < 0.001 ) . The Gleason scores for the isoechoic and hypoechoic cancers were indistinguishable . The pathological staging of hypoechoic and isoechoic cancers was also similar . This study suggests that while isoechoic cancers are generally smaller than hypoechoic cancers , they do not represent low grade clinical ly insignificant carcinomas . A systematic approach to performing prostate biopsy is recommended \n Output:\n " }, { "from": "agent", "value": "Systematic TRUSBx is the gold st and ard , but it fails to detect numerous tumors .\nDiagnostic MR imaging provides more accurate selection of regions in which tumors are suspected .\nUsing these diagnostic images during an MR-directed biopsy procedure improves quality of the biopsy ." } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: PURPOSE To investigate whether sunitinib plus docetaxel improves clinical outcomes for patients with human epidermal growth factor receptor 2 (HER2)/neu-negative advanced breast cancer ( ABC ) versus docetaxel alone . PATIENTS AND METHODS In this phase III study , patients were r and omly assigned to open-label combination therapy ( sunitinib 37.5 mg/d , days 2 to 15 every 3 weeks ; and docetaxel 75 mg/m(2 ) , day 1 every 3 weeks ) or monotherapy ( docetaxel 100 mg/m(2 ) every 3 weeks ) . Progression-free survival ( PFS ) was the primary end point . RESULTS Two hundred ninety-six patients were r and omly assigned to combination therapy , and 297 patients were assigned to monotherapy . Median PFS times were 8.6 and 8.3 months with combination therapy and monotherapy , respectively ( hazard ratio , 0.92 ; one-sided P = .265 ) . The objective response rate ( ORR ) was significantly higher with the combination ( 55 % ) than with monotherapy ( 42 % ; one-sided P = .001 ) . Duration of response was similar in both arms ( 7.5 months with the combination v 7.2 months with monotherapy ) . Median overall survival ( OS ) times were 24.8 and 25.5 months with combination therapy and monotherapy , respectively ( one-sided P = .904 ) . There were 107 deaths with the combination and 91 deaths with monotherapy . The frequency of common adverse events ( AEs ) was higher with the combination , as were treatment discontinuations caused by AEs . CONCLUSION The combination of sunitinib plus docetaxel improved ORR but did not prolong either PFS or OS compared with docetaxel alone when given to an unselected HER2/neu-negative cohort as first-line treatment for ABC . Sunitinib combination therapy may also have result ed in AEs that yield an unfavorable risk-benefit ratio . The sunitinib-docetaxel regimen evaluated in this study is not recommended for further use in ABC BACKGROUND In a phase III trial , 3-weekly capecitabine ( 1250 mg/m(2 ) twice daily days 1 - 14 ) plus docetaxel ( 75 mg/m(2 ) day 1 ) demonstrated significantly superior overall survival to 3-weekly docetaxel ( 100 mg/m(2 ) day 1 ) . We report a retrospective analysis of the impact of capecitabine/docetaxel dose reduction on safety and efficacy . PATIENTS AND METHODS Safety and efficacy data were analyzed retrospectively according to the actual doses of capecitabine and docetaxel administered . RESULTS More patients receiving capecitabine/docetaxel ( 65 % ) had dose reductions for adverse events than docetaxel alone ( 35 % ) . In most patients requiring dose reduction with the combination ( 80 % ) , capecitabine and docetaxel were simultaneously reduced to 950 mg/m(2 ) and 55 mg/m(2 ) , respectively . Subsequently , there were fewer cycles ( 17 % ) with grade 3/4 adverse events than with the full doses ( 34 % ) . Time to progression and overall survival appeared to be similar in patients starting the second cycle with reduced doses of capecitabine/docetaxel and those who continued to receive full doses of capecitabine/docetaxel for at least the first four cycles . CONCLUSIONS Capecitabine/docetaxel dosing flexibility allows management of side-effects without compromising efficacy . This retrospective analysis , as well as multiple phase II studies of taxanes with reduced-dose capecitabine , shows that reducing the starting dose of capecitabine with docetaxel is a reasonable strategy for the treatment of patients with metastatic breast cancer . In addition , reducing the dose of both agents may be appropriate BACKGROUND The purpose of this study was to compare docetaxel plus epirubicin versus docetaxel plus capecitabine combinations as front-line treatment in women with advanced breast cancer ( ABC ) . PATIENTS AND METHODS Previously untreated patients with ABC were r and omly assigned to receive docetaxel 75 mg/m(2 ) plus epirubicin 75 mg/m(2 ) ( DE ) on day 1 or docetaxel 75 mg/m(2 ) on day 1 plus capecitabine 950 mg/m(2 ) orally twice daily on days 1 - 14 ( DC ) in 21-day cycles . Previous anthracycline-based (neo)-adjuvant chemotherapy was allowed if completed > 1 year before enrollment . The primary objective of the study was to compare time to disease progression ( TTP ) . RESULTS One hundred and thirty-six women were treated on each arm and median TTP was 10.6 versus 11.0 months ( P = 0.7 ) , for DE and DC , respectively . According to RECIST criteria we observed 15 ( 11 % ) versus 11 ( 8 % ) complete responses and 55 ( 40 % ) versus 61 ( 45 % ) partial responses ( P = 0.8 ) , with DE and DC , respectively . Severe toxicity included grade 3 - 4 neutropenia ( 57 % versus 46 % ; P = 0.07 ) , febrile neutropenia ( 11 % versus 8 % ; P = 0.4 ) , h and -foot syndrome ( 0 % versus 4 % ; P = 0.02 ) , grade 2 - 3 anemia ( 20 % versus 7 % ; P = 0.001 ) and asthenia ( 12 % versus 6 % ; P = 0.09 ) with DE and DC , respectively . CONCLUSIONS The DE and DC regimens have similar efficacy but different toxicity . Either regimen can be used as front-line treatment of ABC PURPOSE Dexrazoxane was found effective in reducing doxorubicin cardiotoxicity when given at a dose ratio ( dexrazoxane : doxorubicin ) of 20:1 . Pre clinical studies indicated that dexrazoxane at a dose ratio of 10 to 15:1 also protected against epirubicin-induced cardiotoxicity . The main objective of this study was to investigate the efficacy of dexrazoxane , given at a dose ratio of 10:1 against epirubicin cardiotoxicity . PATIENTS AND METHODS One hundred sixty-two advanced breast cancer patients were r and omized to receive epirubicin-based chemotherapy with or without dexrazoxane . Patients who had previously received adjuvant chemotherapy that contained anthracyclines were treated with cyclophosphamide 600 mg/m2 intravenously ( IV ) , epirubicin 60 mg/m2 IV , and fluorouracil 600 mg/m2 IV , on day 1 every 3 weeks . The other patients were treated with epirubicin 120 mg/m2 IV on day 1 every 3 weeks . Cardiac toxicity was defined as clinical signs of congestive heart failure , a decrease in resting left ventricular ejection fraction ( LVEF ) to < or = 45 % , or a decrease from baseline resting LVEF of > or = 20 EF units . RESULTS One hundred sixty patients were evaluated . Cardiotoxicity was recorded in 18 of 78 patients ( 23.1 % ) in the control arm and in six of 82 ( 7.3 % ) in the dexrazoxone arm . The cumulative probability of developing cardiotoxicity was significantly lower in dexrazoxane-treated patients than in control patients ( P = .006 ; odds ratio , 0.29 ; 95 % confidence limit [ CL ] , 0.09 to 0.78 ) . Noncardiac toxicity , objective response , progression-free survival , and overall survival were similar in both arms . CONCLUSION Dexrazoxane given at a dexrazoxane : epirubicin dose ratio of 10:1 protects against epirubicin-induced cardiotoxicity and does not affect the clinical activity and the noncardiac toxicity of epirubicin . The clinical use of dexrazoxane should be recommended in patients whose risk of developing cardiotoxicity could hamper the eventual use and possible benefit of epirubicin Our objective was to determine whether oral etoposide and cisplatin combination ( EoP ) is superior to paclitaxel in the treatment of advanced breast cancer ( ABC ) patients pretreated with anthracyclines . From December 1997 to August 2003 , 201 patients were r and omised , 100 to EoP and 101 to paclitaxel arms . Four patients in each arm were ineligible . The doses of etoposide and cisplatin were 50 mg p.o . twice a day for 7 days and 70 mg m−2 intravenously ( i.v . ) on day 1 , respectively , and it was 175 mg m−2 on day 1 for paclitaxel . Both treatments were repeated every 3 weeks . A median of four cycles of study treatment was given in both arms . The response rate obtained in the EoP arm was significantly higher ( 36.3 vs 22.2 % ; P=0.038 ) . Median response duration was longer for the EoP arm ( 7 vs 4 months ) ( P=0.132 ) . Also , time to progression was significantly in favour of the EoP arm ( 5.5 vs 3.9 months ; P=0.003 ) . Median overall survival was again significantly longer in the EoP arm ( 14 vs 9.5 months ; P=0.039 ) . Toxicity profile of both groups was similar . Two patients in each arm were lost due to febrile neutropenia . The observed activity and acceptable toxicity of EoP endorses the employment of this combination in the treatment of ABC following anthracyclines PURPOSE An American Society of Clinical Oncology ( ASCO ) provisional clinical opinion ( PCO ) offers timely clinical direction to ASCO 's membership following publication or presentation of potentially practice -changing data from major studies . This PCO addresses the integration of palliative care services into st and ard oncology practice at the time a person is diagnosed with metastatic or advanced cancer . CLINICAL CONTEXT Palliative care is frequently misconstrued as synonymous with end-of-life care . Palliative care is focused on the relief of suffering , in all of its dimensions , throughout the course of a patient 's illness . Although the use of hospice and other palliative care services at the end of life has increased , many patients are enrolled in hospice less than 3 weeks before their death , which limits the benefit they may gain from these services . By potentially improving quality of life ( QOL ) , cost of care , and even survival in patients with metastatic cancer , palliative care has increasing relevance for the care of patients with cancer . Until recently , data from r and omized controlled trials ( RCTs ) demonstrating the benefits of palliative care in patients with metastatic cancer who are also receiving st and ard oncology care have not been available . RECENT DATA Seven published RCTs form the basis of this PCO . PROVISIONAL CLINICAL OPINION Based on strong evidence from a phase III RCT , patients with metastatic non-small-cell lung cancer should be offered concurrent palliative care and st and ard oncologic care at initial diagnosis . While a survival benefit from early involvement of palliative care has not yet been demonstrated in other oncology setting s , substantial evidence demonstrates that palliative care-when combined with st and ard cancer care or as the main focus of care-leads to better patient and caregiver outcomes . These include improvement in symptoms , QOL , and patient satisfaction , with reduced caregiver burden . Earlier involvement of palliative care also leads to more appropriate referral to and use of hospice , and reduced use of futile intensive care . While evidence clarifying optimal delivery of palliative care to improve patient outcomes is evolving , no trials to date have demonstrated harm to patients and caregivers , or excessive costs , from early involvement of palliative care . Therefore , it is the Panel 's expert consensus that combined st and ard oncology care and palliative care should be considered early in the course of illness for any patient with metastatic cancer and /or high symptom burden . Strategies to optimize concurrent palliative care and st and ard oncology care , with evaluation of its impact on important patient and caregiver outcomes ( eg , QOL , survival , health care services utilization , and costs ) and on society , should be an area of intense research . NOTE ASCO 's provisional clinical opinions ( PCOs ) reflect expert consensus based on clinical evidence and literature available at the time they are written and are intended to assist physicians in clinical decision making and identify questions and setting s for further research . Because of the rapid flow of scientific information in oncology , new evidence may have emerged since the time a PCO was su bmi tted for publication . PCOs are not continually up date d and may not reflect the most recent evidence . PCOs can not account for individual variation among patients and can not be considered inclusive of all proper methods of care or exclusive of other treatments . It is the responsibility of the treating physician or other health care provider , relying on independent experience and knowledge of the patient , to determine the best course of treatment for the patient . Accordingly , adherence to any PCO is voluntary , with the ultimate determination regarding its application to be made by the physician in light of each patient 's individual circumstances . ASCO PCOs describe the use of procedures and therapies in clinical trials and can not be assumed to apply to the use of these interventions in the context of clinical practice . ASCO assumes no responsibility for any injury or damage to persons or property arising out of \n Output:\n " }, { "from": "agent", "value": "RECOMMENDATIONS Endocrine therapy is preferable to chemotherapy as first-line treatment for patients with estrogen receptor-positive metastatic breast cancer unless improvement is medically necessary ( eg , immediately life-threatening disease ) .\nSingle agent is preferable to combination chemotherapy , and longer planned duration improves outcome but must be balanced against toxicity .\nOther targeted therapies have not so far been shown to enhance chemotherapy outcome in HER2-negative breast cancer" } ]

[ { "from": "human", "value": "***TASK*** the task is to summarize an input biomedical literature in six sentences \n ***INPUT*** the input is a biomedical literature \n ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences \n ***DOCUMENTATION*** \n ***EXAMPLES*** \n Input: PURPOSE In non-small-cell lung cancer ( NSCLC ) , clinical and biologic predictors for epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor sensitivity have been identified in retrospective studies , and there is urgent need to vali date these results in prospect i ve trials . The ONCOBELL trial is a prospect i ve phase II study evaluating gefitinib sensitivity in NSCLC patients who never smoked or have increased EGFR gene copy number or activation of the antiapoptotic protein Akt . PATIENTS AND METHODS EGFR gene copy number was evaluated using fluorescence in situ hybridization ( FISH ) , and presence of phospho-Akt was evaluated using immunohistochemistry . Additional tests included immunohistochemistry analysis of EGFR , FISH analysis of HER2 , and mutation analysis of EGFR , HER2 , and K-ras . RESULTS From November 2004 to February 2006 , 183 patients were screened , and 42 patients were enrolled onto the trial . We observed one complete and 19 partial responses , for an overall response rate ( RR ) of 47.6 % ( 95 % CI , 32.5 % to 62.7 % ) . Median duration of response was 6.1 months , median time to progression ( TTP ) was 6.4 months , 1-year survival rate was 64.3 % , and median survival time was not reached . EGFR FISH-positive patients , compared with negative patients , had higher RR ( 68.0 % v 9.1 % , respectively ; P < .001 ) , longer TTP ( 7.6 v 2.7 months , respectively ; P = .02 ) , and a trend for longer survival ( median survival not reached v 7.4 months , respectively ; P = .3 ) . Therapy was well tolerated , and there were no drug-related deaths . Median follow-up time was too short for significance tests of differences in survival outcomes . CONCLUSION Gefitinib is active and well tolerated in patients with trial characteristics , and EGFR FISH analysis is an accurate predictor for such therapy PURPOSE To evaluate the efficacy and tolerability of two doses of gefitinib ( Iressa [ ZD1839 ] ; AstraZeneca , Wilmington , DE ) , a novel epidermal growth factor receptor tyrosine kinase inhibitor , in patients with pretreated advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS This was a r and omized , double-blind , parallel-group , multicenter phase II trial . Two hundred ten patients with advanced NSCLC who were previously treated with one or two chemotherapy regimens ( at least one containing platinum ) were r and omly assigned to receive either 250-mg or 500-mg oral doses of gefitinib once daily . RESULTS Efficacy was similar for the 250- and 500-mg/d groups . Objective tumor response rates were 18.4 % ( 95 % confidence interval [ CI ] , 11.5 to 27.3 ) and 19.0 % ( 95 % CI , 12.1 to 27.9 ) ; among evaluable patients , symptom improvement rates were 40.3 % ( 95 % CI , 28.5 to 53.0 ) and 37.0 % ( 95 % CI , 26.0 to 49.1 ) ; median progression-free survival times were 2.7 and 2.8 months ; and median overall survival times were 7.6 and 8.0 months , respectively . Symptom improvements were recorded for 69.2 % ( 250 mg/d ) and 85.7 % ( 500 mg/d ) of patients with a tumor response . Adverse events ( AEs ) at both dose levels were generally mild ( grade 1 or 2 ) and consisted mainly of skin reactions and diarrhea . Drug-related toxicities were more frequent in the higher-dose group . Withdrawal due to drug-related AEs was 1.9 % and 9.4 % for patients receiving gefitinib 250 and 500 mg/d , respectively . CONCLUSION Gefitinib showed clinical ly meaningful antitumor activity and provided symptom relief as second- and third-line treatment in these patients . At 250 mg/d , gefitinib had a favorable AE profile . Gefitinib 250 mg/d is an important , novel treatment option for patients with pretreated advanced NSCLC [ corrected PURPOSE Epidermal growth factor receptor ( EGFR ) mutations have been associated with tumor response to treatment with single-agent EGFR inhibitors in patients with relapsed non-small-cell lung cancer ( NSCLC ) . The implication s of EGFR mutations in patients treated with EGFR inhibitors plus first-line chemotherapy are unknown . KRAS is frequently activated in NSCLC . The relationship of KRAS mutations to outcome after EGFR inhibitor treatment has not been described . PATIENTS AND METHODS Previously untreated patients with advanced NSCLC in the phase III TRIBUTE study who were r and omly assigned to carboplatin and paclitaxel with erlotinib or placebo were assessed for survival , response , and time to progression ( TTP ) . EGFR exons 18 through 21 and KRAS exon 2 were sequenced in tumors from 274 patients . Outcomes were correlated with EGFR and KRAS mutations in retrospective subset analyses . RESULTS EGFR mutations were detected in 13 % of tumors and were associated with longer survival , irrespective of treatment ( P < .001 ) . Among erlotinib-treated patients , EGFR mutations were associated with improved response rate ( P < .05 ) and there was a trend toward an erlotinib benefit on TTP ( P = .092 ) , but not improved survival ( P = .96 ) . KRAS mutations ( 21 % of tumors ) were associated with significantly decreased TTP and survival in erlotinib plus chemotherapy-treated patients . CONCLUSION EGFR mutations may be a positive prognostic factor for survival in advanced NSCLC patients treated with chemotherapy with or without erlotinib , and may predict greater likelihood of response . Patients with KRAS-mutant NSCLC showed poorer clinical outcomes when treated with erlotinib and chemotherapy . Further studies are needed to confirm the findings of this retrospective subset analysis Introduction : Relationships between clinical outcomes and epidermal growth factor receptor (EGFR)-related tumor markers were investigated in patients with advanced non-small cell lung cancer . Methods : Patients with stage IIIB/IV non-small cell lung cancer ( 0–2 prior regimens ) received erlotinib ( 150 mg PO per day ) . Response and survival were evaluated , and tumor sample s were assessed by immunohistochemistry ( EGFR , phosphorylated mitogen-activated protein kinase , and phosphorylated AKT protein expression ) , fluorescence in situ hybridization ( FISH ; EGFR gene copy number ) , and DNA sequencing ( EGFR , KRAS gene mutations ) . Results : Among 311 patients , 8 % had a complete/partial response ; the disease control rate was 66 % . Median Overall survival ( OS ) was 6.1 months ; 1-year survival rate was 27.2 % . Two of 4 patients with EGFR mutations had tumor responses , versus 2/68 with wild-type EGFR ( p = 0.014 ) . Progression-free survival ( PFS ) ( HR = 0.31 ) and OS ( HR = 0.33 ) were significantly prolonged in patients with EGFR mutations . Response rate was significantly higher in patients with EGFR FISH-positive ( 17 % ) than FISH-negative tumors ( 6 % ) , and both PFS ( HR = 0.58 ) and OS ( HR = 0.63 ) significantly favored patients with EGFR FISH-positive tumors ; median OS was 8.6 months in the EGFR FISH-positive group . None of 17 patients with a KRAS mutation had a tumor response , but the impact of KRAS mutation status on survival outcomes was of borderline statistical significance . Neither phosphorylated mitogen-activated protein kinase nor phosphorylated AKT immunohistochemistry status had a significant effect on PFS and OS with erlotinib . Conclusions : The presence of EGFR mutations and EGFR FISH-positive tumors may predispose patients to achieving better outcomes on erlotinib , but may have a beneficial impact on prognosis ( irrespective of treatment ) . Prospect i ve , placebo-controlled studies are needed to determine the predictive value of the putative biomarkers Purpose : To examine potential markers of clinical benefit and the effects of erlotinib on the epidermal growth factor receptor ( EGFR ) signaling pathway in advanced non – small cell lung cancer patients refractory to platinum-based chemotherapy . Experimental Design : Patients were given erlotinib ( 150 mg/d ) . Tumor biopsies were done immediately before treatment and in a subgroup of patients after 6 weeks ' treatment . Results : Of 73 evaluable patients , 7 ( 10 % ) had partial response and 28 ( 38 % ) had stable disease . In 53 patients with baseline tumor sample s , no relationship was observed between pretreatment levels of EGFR , phosphorylated (p)-EGFR , p-AKT , p-mitogen-activated protein kinase ( MAPK ) , or p27 and clinical benefit ( i.e. , response , or stable disease ≥12 weeks ) . Tumors from 15 of 57 patients had high EGFR gene copy number , assessed using fluorescence in situ hybridization ( FISH positive ) , 10 of whom had clinical benefit , compared with 5 of 42 FISH-negative patients . FISH-positive patients had longer median progression-free [ 137 versus 43 days , P = 0.002 ; hazard ratio ( HR ) , 0.37 ] and overall ( 226 versus 106 days , P = 0.267 ; HR , 0.70 ) survival than FISH-negative patients . In paired biopsy sample s from 14 patients , p-EGFR ( P = 0.002 ) , p-MAPK ( P = 0.001 ) , and Ki-67 ( P = 0.025 ) levels were significantly reduced after 6 weeks ' treatment . Apoptosis was significantly increased in patients with clinical benefit ( P = 0.029 ) , and may be a marker of clinical benefit . Conclusion : In this study , EGFR FISH-positive status was associated with improved outcome after erlotinib therapy . Erlotinib led to reduced levels of p-EGFR , p-MAPK , and Ki-67 , and stimulated apoptosis in tumor sample s from patients with clinical benefit A number of different clinical characteristics and molecular markers related to epidermal growth factor receptor ( EGFR ) activation have been reported to singly correlate with therapeutic activity of EGFR tyrosine kinase inhibitors ( TKIs ) in advanced non-small cell lung cancer ( NSCLC ) . This study was design ed to evaluate the predictive value on gefitinib outcomes of a comprehensive panel of molecular parameters in advanced NSCLC patients . EGFR and K-ras mutations were detected by direct sequencing on tumor DNA from paraffin embedded sample s. EGFR and HER2 gene copy number was assessed by FISH . EGFR protein expression was quantified by immunohistochemistry . EGFR gene intron 1 polymorphism was assessed on genomic DNA isolated from venous whole blood sample s. Ninety-one patients were prospect ively enrolled and the overall gefitinib response rate was 18.7 % ( 2 complete and 15 partial responses ) . Sex ( p=0.005 ) , non-smoking status ( p=0.010 ) , skin toxicity ( p=0.020 ) , EGFR gene mutations ( p<0.001 ) and EGFR FISH positivity ( p=0.016 ) were found to be associated with gefitinib response . K-ras mutation was detected in only seven non-responder patients . The median overall survival was of 10 months . Only non-smoking status and EGFR intron 1 polymorphism showed a statistically significant correlation with survival ( p=0.031 and 0.044 , respectively ) . In conclusion , we have confirmed the role of EGFR gene mutation as predictor of response to EGFR TKIs . Moreover , EGFR gene copy number and , potentially , also EGFR intron 1 polymorphism could aid in better prediction of EGFR TKI responsiveness in advanced NSCLC PURPOSE Erlotinib is a highly specific epidermal growth factor receptor ( HER1/EGFR ) tyrosine kinase inhibitor . This phase II study of erlotinib in patients with HER1/EGFR-expressing non-small-cell lung cancer previously treated with platinum-based chemotherapy evaluated tumor response , survival , and symptom improvement . PATIENTS AND METHODS Fifty-seven patients received an oral , continuous daily dose of 150 mg of erlotinib . Assessment s of objective response used WHO and Response Evaluation Criteria in Solid Tumors criteria . The European Organization for Research and Treatment of Cancer Quality of Life Question naire C30 , supplemented with a lung cancer module , Quality of Life Question naire LC13 , was used to measure health-related quality of life . Additional analyses were performed to identify predictors of response and survival . RESULTS The objective response \n Output:\n " }, { "from": "agent", "value": "The result of the analysis found that EGFR gene copy number was associated with increased OS and PFS , supporting the idea that EGFR gene copy number is a biomarker for response to EGFR-TKI therapy in patients with advanced NSCLC" } ]