***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: In advanced cancer , when cure is impossible , symptoms should be the focus of attention . We report the first prospect i ve , systematic analysis of the severity of 37 symptoms  in 1000 patients with advanced cancer , using the Paradox relational data base . Pain , easy fatigue , and anorexia were consistently among the 10 most prevalent symptoms associated with cancer at all sites . When pain , anorexia , weakness , anxiety , lack of energy , easy fatigue , early satiety , constipation , and dyspnea were present , 60%-80 % of patients rated them as moderate or severe , i.e. of clinical importance . The most common symptoms were also the most severe . In general the same symptoms were clinical ly important at most primary sites . Clinical ly important dyspnea , hoarseness , hiccough , and dysphagia were more common in men ; anxiety , nausea , vomiting , and early satiety in women . Clinical ly important dyspepsia , nausea , and vomiting occurred more frequently in gynecological cancers The aim of this study was to evaluate a low-dose regimen of megestrol acetate ( MA ; 320 mg/day ) on appetite in advanced cancer patients . Out- patients with far-advanced non-hormone responsive tumours and loss of appetite were r and omised in a phase III trial , with two consecutive phases : a 14-day double-blind placebo controlled phase ( phase A ) and a 76-day open phase ( phase B ) . During phase A , patients were treated with MA , two 160 mg tablets/day , or placebo . In phase B , the MA dose was titrated to clinical response in both groups . Appetite , food intake , body weight , performance status , mood and quality of life were evaluated with st and ardised measures ; patients ' global judgement about treatment efficacy was also requested . Of 42 patients entering the study , 33 ( 17 MA and 16 placebo ) were evaluable for efficacy . The appetite score improved significantly with MA after 7 days ( P = 0.0023 ) , and this effect was still significant at 14 days ( P = 0.0064 ) . Patients judged the treatment with MA effective in 88.2 % of cases ( 14th day ) , whilst placebo was considered effective by 25 % ( P = 0.0003 ) . None of the other measures showed significant changes during treatment . The remarkable effect on appetite evident after 7 days , without serious side-effects , shows that MA can produce significant subjective effects at a low-dose even in patients with far-advanced disease Abstract The aim of this review is to assess the efficacy and safety of megestrol acetate ( MA ) in geriatric cachexia . The paper presented here review s a previously published study of MA use in 69 patients in a r and omized double blind placebo-controlled trial . This paper will also address the underlying pathogenesis of cachexia ( specifically , the role of cytokines ) along with the use of MA , its mechanism of action and its side effects . Objective To compare the effects of MA oral suspension ( O.S. ) , 800 mg/day , versus placebo on weight in geriatric nursing home patients with weight loss or low body weight . Design Twelve weeks , r and omized , double-blind , placebo-controlled trial with a 13-week follow-up period . Patients Northport VAMC Nursing home patients with weight loss of * 5 % of usual body weight over the past 3 months , or body weight 20 % below their ideal body weight . Interventions Patients were r and omly assigned to receive placebo or MA 800 mg/d for 12 weeks and were then followed for 13 weeks off treatment and mortality 4 years post treatment . Measurements Primary outcome -weight and appetite change . Secondary outcome -sense of well being , enjoyment of life , change in depression scale , laboratory nutrition parameters , energy intake counts , body composition , and adverse events . Results At 12 weeks there were no significant differences in weight gain between treatment groups , while MA-treated patients reported significantly greater improvement in appetite , enjoyment of life , and well being . At week 25 ( 3 months after treatment ) , 61.9 % of MA-treated patients had gained * 1.82 kg ( 4 lbs ) compared to 21.7 % of placebo patients . There was no difference in survival between MA and placebo groups . Considering possible confounders , higher initial IL-6 , initial TNFR-p75 levels , and final neutrophil percentage were associated with elevated mortality , whereas higher initial pre-albumin , initial albumin , final pre-albumin , final albumin and final weight gain were associated with decreased death OBJECTIVE We examined the effects of megestrol acetate versus placebo and progressive resistance physical exercise on weight , lean muscle mass , quality of life , ability to exercise , proinflammatory cytokines , and anti-inflammatory cytokines , and their correlations with one another . DESIGN We organized a prospect i ve 20-week , r and omized , double-blind , placebo-controlled pilot trial of hemodialysis patients . SETTING This study took place at the Outpatient Unit of the Northport Veteran Affairs Medical Center . SUBJECTS We studied nine male hemodialysis patients who had two or more of the following : albumin level < 4.0 g/dL , total cholesterol < 150 mg/dL , protein catabolic rate < 0.8 g/kg/day , and predialysis serum urea nitrogen < 60 mg/dL. Their ages were 50 to 83 years . Two were diabetic , and seven were nondiabetic . INTERVENTIONS Interventions included megestrol acetate ( MA ) or placebo 800 mg oral daily for 20 weeks , along with weight resistance physical therapy with weights twice a week before dialysis . Patients were followed prospect ively for an additional 4 weeks . MAIN OUTCOME MEASUREMENTS Weight , body composition , activities of daily living , ability to exercise , and plasma cytokine levels were measured . RESULTS At 24 weeks , the MA group had a statistically significant weight gain ( 11.1-pound increase vs. 1.5-pound decrease for the placebo group , P = .018 ) , body fat gain ( 6.2-pound increase vs. a 0.4-pound decrease for the placebo group , P = .044 ) and fat-free mass gain ( 5-pound increase vs. a 1.2-pound decrease in the placebo group ) . The MA group also had a greater tendency toward increased appetite and sense of well-being . The MA group showed a greater improvement in ability to exercise ( mean change in rate of perceived exertion ( RPE ) , 4.7 ) vs. the placebo group ( mean change in RPE vs. 0.5 , P = .02 ) . Elevated cytokine levels were evident at baseline in both groups . In all patients , increases in weight , fat-free mass , sense of well-being , appetite , and ability to exercise were negatively correlated with tumor necrosis factor receptor subunit p75 ( P < .05 ) . There was a trend toward all of these parameters to be negatively correlated with tumor necrosis factor receptor subunit p55 , although only sense of well-being was statistically significant ( P < .05 ) . CONCLUSION In a pilot trial in dialysis patients , MA showed significant benefits in improving weight and ability to exercise . Cytokine changes were correlated with weight gains and increases in fat-free mass Weight loss is known to impact survival among patients infected with human immunodeficiency virus ( HIV ) even in the era of highly active antiretroviral therapy ( HAART ) . In a r and omized trial , we compared the effects of 2 months of treatment with either megestrol acetate ( 800 mg every day ) or ox and rolone ( 10 mg twice per day ) on body weight and composition in patients with weight loss of > or = 5 kg who were receiving HAART . The mean weight was 66 kg , and the mean body mass index was 21 . Mean weight gain in the megestrol acetate and the ox and rolone arms were 2.8 kg ( 4.6 % of the baseline value ) and 2.5 kg ( 3.9 % of the baseline value ) , respectively ( P=.80 ) . Lean body mass accounted for 39 % of weight gain in the megestrol acetate arm and 56 % in the ox and rolone arm ( P=.38 ) . Seven patients in the megestrol acetate arm and 5 patients in the ox and rolone arm reported minor adverse events ( P=.74 ) . In conclusion , megestrol acetate therapy and ox and rolone therapy have similar effects on body weight and composition and are safe and well-tolerated during HAART OBJECTIVES To determine the independent and combined effects of progressive resistance muscle strength training ( PRMST ) and megestrol acetate ( MA ) on strength , muscle mass , and function in older recuperative care patients . DESIGN Double-blind , r and omized , controlled intervention using a two-by-two factorial design and conducted between 1999 and 2001 . SETTING University-affiliated Department of Veterans Affairs hospital . PARTICIPANTS Twenty-nine patients ( mean age 79.4 + /- 7.4 , 90 % white ) aged 65 and older and had recent functional decline . INTERVENTIONS After r and omization to one of four treatment groups ( low-resistance exercises plus 800 mg per day of MA or a placebo or high-intensity PRMST plus 800 mg/d of MA or placebo ) , subjects received training and the drug or placebo for 12 weeks . MEASUREMENTS Change in muscle strength , mid-thigh muscle area , and aggregate functional performance score as assessed using analysis of covariance . RESULTS Five subjects withdrew from the study before its completion . Based on intent-to-treat analyses , subjects who received high-intensity PRMST and placebo experienced the greatest strength gains . The addition of MA was associated with worse outcomes than with high-intensity exercise training alone , especially with regard to the leg exercises . Post hoc analysis demonstrated that subjects who received high-intensity PRMST and placebo experienced significantly greater percentage increases in leg strength than subjects in either of the MA treatment groups ( P<.05 for each comparison ) . There was also a significant negative effect of MA on physical function . In general , subjects who received MA experienced a deterioration in aggregate physical function scores , whereas the remaining subjects improved ( -0.80+/-0.40 vs 0.48+/-0.41 , P=.04 ) . There was not a significant interaction between exercise and MA for any outcome . CONCLUSION High-intensity PRMST is a safe and well-tolerated exercise regimen for frail elderly patients . The addition of MA appears to blunt the beneficial effects of PRMST , result ing in less muscle strength and functional performance gains This article deals with the extension of the pretest-posttest clinical trial to the longitudinal data setting . We assume that a  baseline ( or pretest ) measurement  is taken on all individuals , who are then r and omized , without regard to baseline values , to a treatment group .  Repeated measurements are taken postr and omization at specified times . Our objective is to estimate the average rate of change ( or slope ) in the experimental groups and the differences in the slopes . Our focus is on the optimal use of the baseline measurements in the analysis . We contrast two different approaches :-- a multivariate one that regards the entire vector of responses ( including the baseline ) as r and om outcomes and a univariate one that uses each individual 's least squares slope as an outcome . Our multivariate approach is essentially a generalization of Stanek 's Seemingly Unrelated Regression ( SUR ) estimator for the pretest-posttest design . The multivariate approach is natural to apply in this setting , and optimal if the assumed model is correct . However , the most efficient estimator requires assuming that the baseline mean parameters are the same for all experimental groups . Although this assumption is reasonable in the r and omized setting , the result ing multivariate estimator uses postr and omization data as a covariate ; if the assumed linear model is not correct , this can lead to distortions in the estimated treatment effect . We propose instead a reduced form multivariate estimator that may be somewhat less efficient , but protects against model misspecification CONTEXT The " St and ards , Options and Recommendations " ( SOR ) project , started in 1993 , is a collaboration between the Federation of the French Cancer Centres ( FNCLCC ) , the 20 French Cancer Centres and specialists from French Public Universities , General Hospitals and Private Clinics . The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients . The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts , with feedback from specialists in cancer care delivery . OBJECTIVES To develop clinical practice guidelines according to the definitions of the St and ards , Options and Recommendations project for the use of appetite stimulants in oncology . METHODS Data were identified by search ing Medline and the personal reference lists of members of the expert groups . Once the guidelines were defined , the document was su bmi tted for review to 55 independent review ers , and to the medical committees of the 20 French Cancer Centres . RESULTS The main recommendations for the use of appetite stimulants in oncology are : 1 ) Corticosteroids and the synthetic progestogens ( megestrol acetate and medroxyprogesterone acetate ) are appetite stimulants . 2 ) They can be useful in managing anorexia and weight loss in cancer patients , especially in the palliative setting , despite the potential side-effects of these agents . 3 ) The most effective way of using these drugs is not known . Inclusion in clinical trials is recommended . 4 ) Cyproheptadine , metoclopramide , n and rolone and pentoxif line should not be used outside prospect i ve clinical tri 
    Output:
    
Meta- analysis showed a benefit of MA compared with placebo , particularly with regard to appetite improvement and weight gain in cancer , AIDS and other underlying conditions , and lack of benefit in the same patients when MA was compared to other drugs .
There was insufficient information to define the optimal dose of MA , but higher doses were more related to weight improvement than lower doses .
Quality of life improvement in patients was seen only when comparing MA versus placebo but not other drugs in both subcategories : cancer and AIDS .
This review shows that MA improves appetite and is associated with slight weight gain in cancer , AIDS and in patients with other underlying pathology .