***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE : To compare the vascular responses to hormone therapy in women with and without hot flushes . METHODS : We r and omly assigned 143 healthy , recently postmenopausal women ( mean age 52.4±0.2 years , time since menopause 19.5±0.9 months ) with intolerable hot flushes ( more than seven moderate/severe episodes per day ) or tolerable hot flushes ( fewer than three mild episodes per day ) to receive 1 mg of transdermal estradiol gel , oral estradiol ( 2 mg ) with and without daily medroxyprogesterone acetate , or placebo for 6 months . Vascular function was assessed by pulse – wave analysis and endothelial function testing with nitroglycerin and salbutamol challenges . RESULTS : Hot flushes did not affect the changes in arterial or aortic stiffness or endothelial function in response to various forms of hormone therapy . However , in women with tolerable hot flushes , oral estrdiol caused a decrease of 13.2 % ( P=.028 ) in the time to the first systolic peak ( dependent on the rapid phase of ventricular ejection ) after nitroglycerin . In addition , the time to the reflected wave ( dependent on pulse – wave velocity ) after nitroglycerin was decreased by 8.4 % ( P=.018 ) . These effects were not seen in women with intolerable hot flushes or with the other treatment regimens . CONCLUSION : Women without troublesome hot flushes are susceptible to unfavorable vascular effects  after oral estrogen treatment , result ing in less compliant vasculature . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00668603 . LEVEL OF EVIDENCE : Although r and omised trials are important for evidence -based medicine , little is known about their overall characteristics . We assessed the epidemiology and reporting of method ological details for all 519 PubMed -indexed r and omised trials published in December , 2000 ( 383 [ 74 % ] parallel-group , 116 [ 22 % ] crossover ) . 482 ( 93 % ) were published in specialty journals . A median of 80 participants ( 10th-90th percentile 25 - 369 ) were recruited for parallel-group trials . 309 ( 60 % ) were blinded . Power calculation , primary outcomes , r and om sequence generation , allocation concealment , and h and ling of attrition were each adequately described in less than half of publications . The small sample sizes are worrying , and poor reporting of method ological characteristics will prevent reliable quality assessment of many published trials BACKGROUND Diet is an important factor in colorectal carcinogenesis ; thus , dietary supplements may have a role in colorectal cancer prevention . OBJECTIVE The objective was to establish the relative luminal , epithelial , and epigenetic consequences of prebiotic , probiotic , and synbiotic dietary supplementation in humans . DESIGN This was a r and omized , double-blind , placebo-controlled , 4-wk crossover trial of resistant starch and Bifidobacterium lactis , either alone or as a combined synbiotic preparation , in 20 human volunteers . Rectal biopsy , feces , and serum sample s were collected . The rectal mucosal endpoints were DNA methylation at 16 CpG isl and loci and LINE-1 , epithelial proliferation ( Ki67 immunohistochemistry ) , and crypt cellularity . The fecal endpoints were short-chain fatty acid concentrations , pH , ammonia , and microbiological profiles ( by denaturing gradient gel electrophoresis and sequencing ) . Serum endpoints were a panel of cytokines and high-sensitivity C-reactive protein . RESULTS Seventeen subjects completed the entire study . The synbiotic intervention fostered a significantly different fecal stream bacterial community than did either the prebiotic ( P = 0.032 ) or the probiotic ( P = 0.001 ) intervention alone , in part because of a greater proportion of patients harboring fecal Lachnospiraceae spp . These changes developed in the absence of any significant differences in fecal chemistry . There were no differences in epithelial kinetics . CONCLUSIONS This synbiotic supplementation with B. lactis and resistant starch , in the doses used , induced unique changes in fecal microflora but did not significantly alter any other fecal , serum , or epithelial variables . This trial was registered in the Australian New Zeal and Clinical Trials Registry at www.anzctr.org.au as ACTRN012606000115538 Traditional nonsteroidal anti-inflammatory drugs are associated with the destabilization of blood pressure ( BP ) control , particularly in hypertensive patients treated with blockers of the renin-angiotensin system . To assess the potential impact of nitric oxide donation , the effects of naproxcinod with naproxen and placebo on changes in BP were compared in a r and omized clinical trial of 916 patients with osteoarthritis after 13 weeks of therapy . In addition , the effects of naproxcinod versus naproxen and placebo on systolic BP in patients with hypertension treated with renin-angiotensin system blockers were evaluated . Naproxcinod 750 mg twice daily reduced systolic BP compared to naproxen 500 mg twice daily ( p < 0.02 ) . The 2 doses of naproxcinod showed reductions from baseline in diastolic BP relative to naproxen ( p < 0.04 ) and similar changes compared to placebo . In 207 patients with hypertension treated with renin-angiotensin-blocking agents alone or with diuretics , the difference in mean change from baseline in systolic BP between naproxen 500 mg and naproxcinod 750 mg was 6.5 mm Hg in favor of naproxcinod ( p < 0.02 ) . The proportion of patients in the overall population with systolic BP increases > or = 10 mm Hg was greater with naproxen 500 mg ( 22 % ) compared to naproxcinod 750 mg ( 14 % , p = 0.04 ) , naproxcinod 375 mg ( 14 % , p = 0.055 ) , and placebo ( 15.6 % , p = 0.155 ) . In conclusion , naproxcinod did not induce elevations of BP seen with naproxen , and it had similar effects on BP to that of placebo in patients with osteoarthritis BACKGROUND R and omized efficacy clinical trials conducted in research setting s may not accurately reflect the benefits of tobacco dependence treatments when used in real-world clinical setting s. Effectiveness trials ( eg , in primary care setting s ) are needed to estimate the benefits of cessation treatments in real-world use . METHODS A total of 1346 primary care patients attending routine appointments were recruited by medical assistants in 12 primary care clinics . Patients were r and omly assigned to 5 active pharmacotherapies : 3 monotherapies ( nicotine patch , nicotine lozenge , and bupropion hydrochloride sustained release [ SR ] ) and 2 combination therapies ( patch + lozenge and bupropion SR + lozenge ) . Patients were referred to a telephone quit line for cessation counseling . Primary outcomes included 7-day point prevalence abstinence at 1 week , 8 weeks , and 6 months after quitting and number of days to relapse . RESULTS Among 7128 eligible smokers ( > or = 10 cigarettes per day ) attending routine primary care appointments , 1346 ( 18.9 % ) were enrolled in the study .  Six-month abstinence rates for the 5 active pharmacotherapies were the following : bupropion SR , 16.8 % ; lozenge , 19.9 % ; patch , 17.7 % ; patch + lozenge , 26.9 % ; and bupropion SR + lozenge , 29.9 % . Bupropion SR + lozenge was superior to all of the monotherapies ( odds ratio , 0.46 - 0.56 ) ; patch + lozenge was superior to patch and bupropion monotherapies ( odds ratio , 0.56 and 0.54 , respectively ) . CONCLUSIONS One in 5 smokers attending a routine primary care appointment was willing to make a serious quit attempt that included evidence -based counseling and medication . In this comparative effectiveness study of 5 tobacco dependence treatments , combination pharmacotherapy significantly increased abstinence compared with monotherapies . Provision of free cessation medications plus quit line counseling arranged in the primary care setting holds promise for assisting large numbers of smokers to quit . Trial Registration clinical trials.gov Identifier : NCT00296647 Reports of cluster r and omised trials require additional information to allow readers to interpret them accurately The effective reporting of r and omised controlled trials has received useful attention in recent years . Many journals now require that reports conform to the guidelines in the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement , first published in 1996 and revised in 2001 . The statement includes a checklist of items that should be included in the trial report . These items are evidence based whenever possible and are regularly review ed . The statement also recommends including a flow diagram to show the flow of participants from group assignment through to the final analysis . The CONSORT statement focused on reporting parallel group r and omised trials in which individual participants are r and omly assigned to study groups . However , in some situations it is preferable to r and omly assign groups of individuals ( such as families or medical practice s ) rather than individuals . Reasons include the threat of contamination of some interventions ( such as dietary interventions ) if individual r and omisation is used . 5 Also , in certain setting s r and omisation by group may be the only feasible method of conducting a trial . Trials with this design are variously known as field trials , community based trials , place based trials , or ( as in this paper ) cluster r and omised trials . In an earlier discussion paper we considered the implication s of the CONSORT statement for the reporting of cluster r and omised trials . Here we present up date d guidance , based on the 2001 revision of the CONSORT statement BACKGROUND The possible advantage for weight loss of a diet that emphasizes protein , fat , or carbohydrates has not been established , and there are few studies that extend beyond 1 year . METHODS We r and omly assigned 811 overweight adults to one of four diets ; the targeted percentages of energy derived from fat , protein , and carbohydrates in the four diets were 20 , 15 , and 65 % ; 20 , 25 , and 55 % ; 40 , 15 , and 45 % ; and 40 , 25 , and 35 % . The diets consisted of similar foods and met guidelines for cardiovascular health . The participants were offered group and individual instructional sessions for 2 years . The primary outcome was the change in body weight after 2 years in two-by-two factorial comparisons of low fat versus high fat and average protein versus high protein and in the comparison of highest and lowest carbohydrate content . RESULTS At 6 months , participants assigned to each diet had lost an average of 6 kg , which represented 7 % of their initial weight ; they began to regain weight after 12 months . By 2 years , weight loss remained similar in those who were assigned to a diet with 15 % protein and those assigned to a diet with 25 % protein ( 3.0 and 3.6 kg , respectively ) ; in those assigned to a diet with 20 % fat and those assigned to a diet with 40 % fat ( 3.3 kg for both groups ) ; and in those assigned to a diet with 65 % carbohydrates and those assigned to a diet with 35 % carbohydrates ( 2.9 and 3.4 kg , respectively ) ( P>0.20 for all comparisons ) . Among the 80 % of participants who completed the trial , the average weight loss was 4 kg ; 14 to 15 % of the participants had a reduction of at least 10 % of their initial body weight . Satiety , hunger , satisfaction with the diet , and attendance at group sessions were similar for all diets ; attendance was strongly associated with weight loss ( 0.2 kg per session attended ) . The diets improved lipid-related risk factors and fasting insulin levels . CONCLUSIONS Reduced-calorie diets result in clinical ly meaningful weight loss regardless of which macronutrients they emphasize . ( Clinical Trials.gov number , NCT00072995 . OBJECTIVE To evaluate the efficacy of different antipyretic agents and their highest recommended doses for preventing febrile seizures . DESIGN R and omized , placebo-controlled , double-blind trial . SETTING Five hospitals , each working as the only pediatric hospital in its region . PARTICIPANTS A total of 231 children who experienced their first febrile seizure between January 1 , 1997 , and December 31 , 2003 . The children were observed for 2 years . INTERVENTIONS All febrile episodes during follow-up were treated first with either rectal diclofenac or placebo . After 8 hours , treatment was continued with oral ibuprofen , acetaminophen , or placebo . MAIN OUTCOME MEASURE Recurrence of febrile seizures . RESULT 
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Conclusions Our findings highlight discrepancies between the planning and reporting of analyses in reports of multiple-arm trials