***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background — Smoking cessation is a key component of secondary cardiovascular disease prevention . Varenicline , a partial & agr;4&bgr;2 nicotinic acetylcholine receptor agonist , is effective for smoking cessation in healthy smokers , but its efficacy and safety in smokers with cardiovascular disease are unknown . Methods and Results — A multicenter , r and omized , double-blind , placebo-controlled trial compared the efficacy and safety of varenicline with placebo for smoking cessation in 714 smokers with stable cardiovascular disease . Participants received varenicline ( 1 mg twice daily ) or placebo , along with smoking-cessation counseling , for 12 weeks . Follow-up lasted 52 weeks . The primary end point was carbon monoxide – confirmed continuous abstinence rate for weeks 9 through 12 ( last 4 weeks of treatment ) . The continuous abstinence rate was higher for varenicline than placebo during weeks 9 through 12 ( 47.0 % versus 13.9 % ; odds ratio , 6.11 ; 95 % confidence interval [ CI ] , 4.18 to 8.93 ) and weeks 9 through 52 ( 19.2 % versus 7.2 % ; odds ratio , 3.14 ; 95 % CI , 1.93 to 5.11 ) . The varenicline and placebo groups did not differ significantly in cardiovascular mortality ( 0.3 % versus 0.6 % ; difference , −0.3 % ; 95 % CI , −1.3 to 0.7 ) , all-cause mortality ( 0.6 % versus 1.4 % ; difference , −0.8 % ; 95 % CI , −2.3 to 0.6 ) , cardiovascular events ( 7.1 % versus 5.7 % ; difference , 1.4 % ; 95 % CI , −2.3 to 5.0 ) , or serious adverse events ( 6.5 % and 6.0 % ; difference , 0.5 % ; 95 % CI , −3.1 to 4.1 ) . As a result of adverse events , 9.6 % of varenicline and 4.3 % of placebo participants discontinued study drug . Conclusions — Varenicline is effective for smoking cessation in smokers with cardiovascular disease . It was well tolerated and did not increase cardiovascular events or mortality ; however , trial size and duration limit definitive conclusions about safety . Clinical Trial Registration Information— URL : http://www . clinical trials.gov/ct2/show/NCT00282984 . Unique identifier : NCT00282984 BACKGROUND Currently available smoking cessation therapies have limited success rates . Varenicline tartrate is a novel , selective nicotinic receptor partial agonist developed specifically for smoking cessation . This study evaluated the efficacy , tolerability , and safety of 3 varenicline doses for smoking cessation . Bupropion hydrochloride was included as an active control . METHODS A phase 2 , multicenter , r and omized , double-blind , placebo-controlled study of healthy smokers ( 18 - 65 years old ) . Subjects were r and omized to varenicline tartrate , 0.3 mg once daily ( n = 128 ) , 1.0 mg once daily ( n = 128 ) , or 1.0 mg twice daily ( n = 127 ) , for 6 weeks plus placebo for 1 week ; to 150-mg sustained-release bupropion hydrochloride twice daily ( n = 128 ) for 7 weeks ; or to placebo ( n = 127 ) for 7 weeks . RESULTS During the treatment phase , the continuous quit rates for any 4 weeks were significantly higher for varenicline tartrate , 1.0 mg twice daily ( 48.0 % ; P<.001 ) and 1.0 mg once daily ( 37.3 % ; P<.001 ) , than for placebo ( 17.1 % ) . The  bupropion  rate was 33.3 % ( P = .002 vs placebo ) . The carbon monoxide-confirmed continuous quit rates from week 4 to week 52 were significantly higher in the varenicline tartrate , 1.0 mg twice daily , group compared with the placebo group ( 14.4 % vs 4.9 % ; P = .002 ) . The  bupropion rate was 6.3 % ( P = .60 vs placebo ) . Discontinuation owing to treatment-emergent adverse events was 15.9 % for bupropion , 11.2 % to 14.3 % for varenicline , and 9.8 % for placebo . No dose-related increases occurred in adverse events for varenicline . CONCLUSIONS Varenicline tartrate demonstrated both short-term ( 1 mg twice daily and 1 mg once daily ) and long-term efficacy ( 1 mg twice daily ) vs placebo . Varenicline was well tolerated and may provide a novel therapy to aid smoking cessation STUDY OBJECTIVES To evaluate the cost-effectiveness of an additional 12-week treatment with varenicline for abstainers who had successfully completed an initial 12-week treatment . DESIGN The Benefits of Smoking Cessation on Outcomes simulation model was used to simulate both direct and indirect effects of smoking cessation . All calculations were performed in 2003 Swedish prices . SETTING Sweden in 2003 . PATIENTS OR PARTICIPANTS The modelled cohort consisted of 25 % of adult smokers motivated to quit smoking ( 168,844 males and 208,737 females ) . The age and sex distributions of the cohort reflect that of the Swedish population in 2003 . INTERVENTIONS Smokers who had achieved abstinence for at least 7 days following 12-week open-label treatment with varenicline were r and omized to receive an additional 12-week treatment with either varenicline or placebo . MEASUREMENTS AND RESULTS The incremental costs per quality -adjusted life-year ( QALY ) gained , for abstainers who received an additional 12-week varenicline treatment compared with only 12 weeks , were Euro 7066 for men and Euro 7108 for women , over a 50-year time horizon . ( 1 Euro approximately equal to SEK 9.12 ) . These estimates excluded indirect effects on production and consumption of increased survival . The corresponding incremental costs per QALY including indirect effects were Euro 24,149 and Euro 24,436 , respectively . Sensitivity analysis indicated that the estimated cost-utility ratios are robust , but relatively sensitive to treatment efficiency and intervention costs . CONCLUSIONS An additional 12-week course of varenicline treatment , provided to abstainers after an initial 12-week treatment , produces relatively low incremental cost-utility ratios in the spectrum of life-saving medical treatments Background Smoking is the leading cause of preventable death in the US . While one in five individuals smoke , and 70 % of these indicate a desire to quit , < 5 % of unaided quit attempts succeed . Cessation aids can double or triple the odds of successfully quitting . Models of smoking-cessation behaviour can eluci date the implication s of individual abstinence patterns to allow better tailoring of quit attempts to an individual ’s characteristics . Objective The objectives of this study were to develop and vali date a discrete-event simulation ( DES ) to evaluate the benefits of smoking abstinence using data from the pooled pivotal clinical trials of varenicline versus bupropion or placebo for smoking cessation and to provide a foundation for the development of a lifetime smoking-cessation model . Methods The DES model simulated the outcome of a single smoking-cessation attempt over 1 year , in accordance with the clinical trial timeframes . Pharmaceutical costs were assessed from the perspective of a healthcare payer . The model r and omly sample d patient profiles from the pooled varenicline clinical trials . All patients were physically and mentally healthy adult smokers who were motivated to quit abruptly . The model allowed for comparisons of up to five distinct treatment approaches for smoking cessation . In the current analyses , three interventions corresponding to the clinical trials were evaluated , which included brief counselling plus varenicline 1.0 mg twice daily ( bid ) or bupropion SR 150 mg bid versus placebo ( i.e. brief counselling only ) . The treatment periods in the clinical trials were 12 weeks ( target quit date : day 8) , with a 40-week non-treatment follow-up , and counselling continuing over the entire 52-week period in all treatment groups . The main outcome modelled was the continuous abstinence rate ( CAR ; defined as complete abstinence from smoking and confirmed by exhaled carbon monoxide ≤10 ppm ) at end of treatment ( weeks 9–12 ) and long-term follow-up ( weeks 9–52 ) , and total time abstinent from smoking over the course of 52 weeks . The model also evaluated costs and cost-effectiveness outcomes . Results For the varenicline , bupropion and placebo cohorts , respectively , the model predicted CARs for weeks 9–12 of 44.3 % , 30.4 % and 18.6 % compared with observed rates of 44.0 % , 29.7 % and 17.7 % ; over weeks 9–52 , predicted CARs in the model compared with observed rates in the pooled clinical studies were 22.9 % , 16.4 % and 9.4 % versus 22.4 % , 15.4 % and 9.3 % , respectively . Total mean abstinence times accrued in the model varenicline , bupropion and placebo groups , respectively , were 3.6 , 2.6 and 1.5 months and total pharmaceutical treatment costs were $ US261 , $ US442 and $ US0 ( year 2008 values ) over the 1-year model period . Using cost per abstinent-month achieved as a measure of cost effectiveness , varenicline dominated bupropion and yielded an incremental cost-effectiveness ratio of $ US124 compared with placebo . Conclusion The model accurately replicated abstinence patterns observed in the clinical trial data using individualized predictions and indicated that varenicline was more effective and may be less costly than bupropion . This simulation incorporated individual predictions of abstinence and relapse , and provides a framework for lifetime modelling that considers multiple quit attempts over time in diverse patient population s using a variety of quit attempt strategies Background Numerous explanatory r and omized trials support the efficacy of chronic disease interventions , including smoking cessation treatments . However , there is often inadequate adoption of these interventions for various reasons , one being the limitation of generalizability of the explanatory studies in real-world setting s. R and omized controlled trials can be rated as more explanatory versus pragmatic along 10 dimensions . Pragmatic r and omized clinical trials generate more realistic estimates of effectiveness with greater relevance to clinical practice and for health re source allocation decisions . However , there is no clear method to scale each dimension during the trial design phase to ensure that the design matches the intended purpose of the study . Methods We design ed a  pragmatic , r and omized , controlled study to maximize external validity by addressing several barriers to  smoking cessation therapy in ambulatory care . We analyzed our design and methods using the recently published ‘ Pragmatic – Explanatory Continuum Indicatory Summary ( PRECIS ) ’ tool , a qualitative method to assess trial design across 10 domains . We added a 20-point numerical rating scale and a modified Delphi process to improve consensus in rating these domains . Results After two rounds of review , there was consensus on all 10 domains of study design . No single domain was scored as either fully pragmatic or fully explanatory ; but overall , the study scored high on pragmatism . Conclusions This addition to the PRECIS tool may assist other trial design ers working with interdisciplinary co-investigators to rate their study design while building consensus Pre clinical research and learning theory suggest that a longer duration of varenicline treatment prior to the target quit date ( TQD ) would reduce smoking rates before cessation and improve abstinence outcomes . A double‐blind r and omized controlled trial tested this hypothesis in 60 smokers r and omized to either an Extended run‐in group ( 4 weeks of pre‐TQD varenicline ) or a St and ard run‐in group ( 3 weeks of placebo , 1 week of pre‐TQD varenicline ) ; all the participants received  11 weeks of post‐TQD varenicline and brief counseling . During the pre‐quit run‐in , the reduction in smoking rates was greater in the Extended run‐in group than in the St and ard run‐in group ( 42 % vs. 24 % , P < 0.01 ) , and this effect was greater in women than in men ( 57 % vs. 26 % , P = 0.001 ) . The rate of continuous abstinence during the final 4 weeks of treatment was higher among women in the Extended group compared to women in the St and ard run‐in group ( 67 % vs. 35 % ) . Although these data suggest that extension of varenicline  treatment reduces smoking during the pre‐quit period and may further enhance cessation rates , confirmatory evidence is needed from phase III clinical trials Rationale Varenicline , an approved smoking cessation pharmacotherapy , also shows promise as a potential treatment for alcohol dependence . However , varenicline has not been tested in heavy drinkers , and it remains to be determined whether varenicline could reduce alcohol craving and consumption in smokers who are trying to quit 
    Output:
    
St and ard-dose varenicline treatment was associated with significantly higher rates of headache , insomnia and nausea than placebo ; there was no significant difference in the rates of abnormal dreams .
Using expected values , cytisine is anticipated to dominate varenicline , in that it produces more quality -adjusted life-years at a lower associated cost .
On the basis of the evidence included in this review , varenicline and cytisine are both effective interventions to aid smoking cessation when compared with placebo .
Cytisine is estimated to be both more clinical ly effective and cost-effective than varenicline .
However , there is uncertainty in the decision , and a head-to-head trial of cytisine and varenicline would appear to be an effective use of re sources .