***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: To assess the stability of intention to quit smoking , 115 US and Swedish smokers were r and omized to complete Stage of Change ( SOC ) or ladder scales of intentions to quit at either 0 , 7 , 14 and 30 days or at 0 and 30 days in the absence of intervention . The four- assessment group had more progression in intention to quit than the two- assessment group . Depending on the measure , 12 - 17 % of smokers changed their intention to quit over 7 days , 15 - 25 % changed over 14 days and 17 - 34 % changed over 30 days . Results were similar in Swedish and US participants and replicate the results of prior studies . We conclude intention to quit often spontaneously changes over short periods of time , especially with repeated testing Objective The Question naire on Smoking Urges is now very widely used as a measure of craving but is considerably longer than alternatives in current use . Longer scales carry a significant cost in studies and clinical practice . This study compared the ten-item Question naire on Smoking Urges ( QSU-brief ) with six shorter measures of craving in terms of sensitivity to abstinence and reliability . Methods Sixty smokers were r and omly assigned to  continue smoking ( N = 30 ) or abstain completely for 24 h ( n = 30 ) , by which time the craving would be expected to have increased . Craving was measured at baseline and after 24 h. The craving measures tested were the QSU-brief , the  Minnesota Nicotine Withdrawal Scale ( MNWS ) , the Mood and Physical Symptoms Scale ( MPSS ) , the Shiffman Scale ( SS ) , the Wisconsin Smoking Withdrawal Scale and the Cigarette Withdrawal Scale and a simple rating of ‘ craving ’ ( CR ) . Results All measures showed significant increases in scores following smoking abstinence . The two-item MPSS measure was similar to the QSU-brief ( eta-squared 0.41 versus 0.45 , respectively ) , and the CR was only slightly lower ( eta-squared 0.37 ) . The MNWS showed the least sensitivity ( eta-squared 0.22 ) . Stability while still smoking was good with the exception of the SS which showed a significant reduction on retest . Conclusions The ten-item QSU-brief is not more sensitive to abstinence or reliable than the two-item MPSS or a single rating of craving BACKGROUND Substantial concerns have been raised about the neuropsychiatric safety of the smoking cessation medications varenicline and bupropion . Their efficacy relative to nicotine patch largely relies on indirect comparisons , and there is limited information on safety and efficacy in smokers with psychiatric disorders . We compared the relative neuropsychiatric safety risk and efficacy of varenicline and bupropion with nicotine patch and placebo in smokers with and without psychiatric disorders . METHODS We did a r and omised , double-blind , triple-dummy , placebo-controlled and active-controlled ( nicotine patch ; 21 mg per day with taper ) trial of varenicline ( 1 mg twice a day ) and bupropion ( 150 mg twice a day ) for 12 weeks with 12-week non-treatment follow-up done at 140 centres ( clinical trial centres , academic centres , and outpatient clinics ) in 16 countries between Nov 30 , 2011 , and Jan 13 , 2015 . Participants were motivated-to-quit smokers with and without psychiatric disorders who received brief cessation counselling at each visit . R and omisation was computer generated ( 1:1:1:1 ratio ) . Participants , investigators , and research personnel were masked to treatment assignments . The primary endpoint was the incidence of a composite measure of moderate and severe neuropsychiatric adverse events . The main efficacy endpoint was biochemically confirmed continuous abstinence for weeks 9 - 12 . All participants r and omly assigned were included in the efficacy analysis and those who received treatment were included in the safety analysis . The trial is registered at Clinical Trials.gov ( number NCT01456936 ) and is now closed . FINDINGS 8144 participants were r and omly assigned , 4116 to the psychiatric cohort ( 4074 included in the safety analysis ) and 4028 to the non-psychiatric cohort ( 3984 included in the safety analysis ) . In the non-psychiatric cohort , 13 ( 1·3 % ) of 990 participants reported moderate and severe neuropsychiatric adverse events in the varenicline group , 22 ( 2·2 % ) of 989 in the bupropion group , 25 ( 2·5 % ) of 1006 in the nicotine patch group , and 24 ( 2·4 % ) of 999 in the placebo group . The varenicline-placebo and  bupropion-placebo risk differences ( RDs ) for moderate and severe neuropsychiatric adverse events were -1·28 ( 95 % CI -2·40 to -0·15 ) and -0·08 ( -1·37 to 1·21 ) , respectively ; the RDs for comparisons with nicotine patch were -1·07 ( -2·21 to 0·08 ) and 0·13 ( -1·19 to 1·45 ) , respectively . In the psychiatric cohort , moderate and severe neuropsychiatric adverse events were reported in 67 ( 6·5 % ) of 1026 participants in the varenicline group , 68 ( 6·7 % ) of 1017 in the bupropion group , 53 ( 5·2 % ) of 1016 in the nicotine patch group , and 50 ( 4·9 % ) of 1015 in the placebo group . The varenicline-placebo  and bupropion-placebo RDs were 1·59 ( 95 % CI -0·42 to 3·59 ) and 1·78 ( -0·24 to 3·81 ) , respectively ; the RDs versus nicotine patch were 1·22 ( -0·81 to 3·25 ) and 1·42 ( -0·63 to 3·46 ) , respectively  . Varenicline-treated participants achieved higher abstinence rates than those on placebo ( odds ratio [ OR ] 3·61 , 95 % CI 3·07 to 4·24 ) , nicotine patch ( 1·68 , 1·46 to 1·93 ) , and bupropion ( 1·75 , 1·52 to 2·01 ) . Those on bupropion and nicotine patch achieved higher abstinence rates than those on placebo ( OR 2·07 [ 1·75 to 2·45 ] and 2·15 [ 1·82 to 2·54 ] , respectively ) . Across cohorts , the most frequent adverse events by treatment group were nausea  ( varenicline , 25 % [ 511 of 2016 participants ] ) , insomnia  ( bupropion , 12 % [ 245 of 2006 participants ] ) , abnormal dreams  ( nicotine patch , 12 % [ 251 of 2022 participants ] ) , and headache ( placebo , 10 % [ 199 of 2014 participants ] ) . Efficacy treatment comparison did not differ by cohort . INTERPRETATION The study did not show a significant increase in neuropsychiatric adverse events  attributable to varenicline or bupropion relative to nicotine patch or placebo . Varenicline was more effective than placebo , nicotine patch , and bupropion in helping smokers achieve abstinence , whereas bupropion and nicotine patch were more effective than placebo . FUNDING Pfizer and GlaxoSmithKline Abstract Objective To compare the hazards of cigarette smoking in men who formed their habits at different periods , and the extent of the reduction in risk when cigarette smoking is stopped at different ages . Design Prospect i ve study that has continued from 1951 to 2001 . Setting United Kingdom . Participants 34 439 male British doctors . Information about their smoking habits was obtained in 1951 , and periodically thereafter ; cause specific mortality was monitored for 50 years . Main outcome measures Overall mortality by smoking habit , considering separately men born in different periods . Results The excess mortality associated with smoking chiefly involved vascular , neoplastic , and respiratory diseases that can be caused by smoking . Men born in 1900 - 1930 who smoked only cigarettes and continued smoking died on average about 10 years younger than lifelong non-smokers . Cessation at age 60 , 50 , 40 , or 30 years gained , respectively , about 3 , 6 , 9 , or 10 years of life expectancy . The excess mortality associated with cigarette smoking was less for men born in the 19th century and was greatest for men born in the 1920s . The cigarette smoker versus non-smoker probabilities of dying in middle age ( 35 - 69 ) were 42 % ν24 % ( a twofold death rate ratio ) for those born in 1900 - 1909 , but were 43 % ν 15 % ( a threefold death rate ratio ) for those born in the 1920s . At older ages , the cigarette smoker versus non-smoker probabilities of surviving from age 70 to 90 were 10 % ν 12 % at the death rates of the 1950s ( that is , among men born around the 1870s ) but were 7 % ν 33 % ( again a threefold death rate ratio ) at the death rates of the 1990s ( that is , among men born around the 1910s ) . Conclusion A substantial progressive decrease in the mortality rates among non-smokers over the past half century ( due to prevention and improved treatment of disease ) has been wholly outweighed , among cigarette smokers , by a progressive increase in the smoker ν non-smoker death rate ratio due to earlier and more intensive use of cigarettes . Among the men born around 1920 , prolonged cigarette smoking from early adult life tripled age specific mortality rates , but cessation at age 50 halved the hazard , and cessation at age 30 avoided almost all of it Background The use of nicotine replacement therapy before quitting smoking is called nicotine preloading . St and ard smoking cessation protocol s suggest commencing nicotine replacement therapy only on the first day of quitting smoking ( quit day ) aim ing to reduce withdrawal symptoms and craving . However , other , more successful smoking cessation pharmacotherapies are used prior to the quit day as well as after . Nicotine preloading could improve quit rates by reducing satisfaction from smoking prior to quitting and breaking the association between smoking and reward . A systematic literature review suggests that evidence for the effectiveness of preloading is inconclusive and further trials are needed . Methods / Design This is a study protocol for a multicenter , non-blinded , r and omized controlled trial based in the United Kingdom , enrolling 1786 smokers who want to quit , funded by the National Institute for Health Research , Health Technology Assessment program , and sponsored by the University of Oxford . Participants will primarily be recruited through general practice s and smoking cessation clinics , and r and omized ( 1:1 ) either to use 21 mg nicotine patches  , or  not  , for four weeks before quitting , whilst smoking as normal . All participants will be referred to receive st and ard smoking cessation service support . Follow-ups will take place at one week , four weeks , six months and 12 months after quit day . The primary outcome will be prolonged , biochemically verified six-month abstinence . Additional outcomes will include point prevalence abstinence and abstinence of four-week and 12-month duration , side effects , costs of treatment , and markers of potential mediators and moderators of the preloading effect . Discussion This large trial will add substantially to evidence on the effectiveness of nicotine preloading , but also on its cost effectiveness and potential mediators , which have not been investigated in detail previously . A range of recruitment strategies have been considered to try and compensate for any challenges encountered in recruiting the large sample , and the multicentre design means that knowledge can be shared between recruitment teams . The pragmatic study design means that results will give a realistic estimate of the success of the intervention if it were to be rolled out as part of st and ard smoking cessation service practice .Trial registration Current Controlled Trials IS RCT N33031001 . Registered 27 April 2012 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 
    Output:
    
There was evidence that reduced urges to smoke and reduced smoke inhalation mediated the effect of preloading on abstinence .
Use of nicotine-patch preloading for 4 weeks prior to attempting to stop smoking can increase the proportion of people who stop successfully , but its benefit is undermined because it reduces the use of varenicline after preloading .
If this latter effect could be overcome , then nicotine preloading appears to improve health and reduce health-service costs in the long term .