Amanda Parsons

Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis

Objective To systematically review the evidence that smoking cessation after diagnosis of a primary lung tumour affects prognosis. Design Systematic review with meta-analysis. Data sources CINAHL (from 1981), Embase (from 1980), Medline (from 1966), Web of Science (from 1966), CENTRAL (from 1977) to December 2008, and reference lists of included studies. Study selection Randomised controlled trials or observational longitudinal studies that measured the effect of quitting smoking after diagnosis of lung cancer on prognostic outcomes, regardless of stage at presentation or tumour histology, were included. Data extraction Two researchers independently identified studies for inclusion and extracted data. Estimates were combined by using a random effects model, and the I2 statistic was used to examine heterogeneity. Life tables were used to model five year survival for early stage non-small cell lung cancer and limited stage small cell lung cancer, using death rates for continuing smokers and quitters obtained from this review. Results In 9/10 included studies, most patients studied were diagnosed as having an early stage lung tumour. Continued smoking was associated with a significantly increased risk of all cause mortality (hazard ratio 2.94, 95% confidence interval 1.15 to 7.54) and recurrence (1.86, 1.01 to 3.41) in early stage non-small cell lung cancer and of all cause mortality (1.86, 1.33 to 2.59), development of a second primary tumour (4.31, 1.09 to 16.98), and recurrence (1.26, 1.06 to 1.50) in limited stage small cell lung cancer. No study contained data on the effect of quitting smoking on cancer specific mortality or on development of a second primary tumour in non-small cell lung cancer. Life table modelling on the basis of these data estimated 33% five year survival in 65 year old patients with early stage non-small cell lung cancer who continued to smoke compared with 70% in those who quit smoking. In limited stage small cell lung cancer, an estimated 29% of continuing smokers would survive for five years compared with 63% of quitters on the basis of the data from this review. Conclusions This review provides preliminary evidence that smoking cessation after diagnosis of early stage lung cancer improves prognostic outcomes. From life table modelling, the estimated number of deaths prevented is larger than would be expected from reduction of cardiorespiratory deaths after smoking cessation, so most of the mortality gain is likely to be due to reduced cancer progression. These findings indicate that offering smoking cessation treatment to patients presenting with early stage lung cancer may be beneficial.

Brief opportunistic smoking cessation interventions: A systematic review and meta-analysis to compare advice to quit and offer of assistance

AIMS This study aimed to assess the effects of opportunistic brief physician advice to stop smoking and offer of assistance on incidence of attempts to stop and quit success in smokers not selected by motivation to quit. METHODS We included relevant trials from the Cochrane Reviews of physician advice for smoking cessation, nicotine replacement therapy (NRT), varenicline and bupropion. We extracted data on quit attempts and quit success. Estimates were combined using the Mantel-Haentszel method and heterogeneity assessed with the I(2) statistic. Study quality was assessed by method of randomization, allocation concealment and follow-up blind to allocation. RESULTS Thirteen studies were included. Compared to no intervention, advice to quit on medical grounds increased the frequency of quit attempts [risk ratio (RR) 1.24, 95% confidence interval (CI): 1.16-1.33], but not as much as behavioural support for cessation (RR 2.17, 95% CI 1.52-3.11) or offering NRT (RR 1.68, 95% CI: 1.48-1.89). In a direct comparison, offering assistance generated more quit attempts than giving advice to quit on medical grounds (RR 1.69, 95% CI: 1.24-2.31 for behavioural support and 1.39, 95% CI: 1.25-1.54 for offering medication). There was evidence that medical advice increased the success of quit attempts and inconclusive evidence that offering assistance increased their success. CONCLUSIONS Physicians may be more effective in promoting attempts to stop smoking by offering assistance to all smokers than by advising smokers to quit and offering assistance only to those who express an interest in doing so.

The effect of Transtheoretical Model based interventions on smoking cessation

The Transtheoretical Model (TTM) proposes that stage matching improves the effectiveness of behaviour change interventions, such as for smoking cessation. It also proposes that standard smoking cessation interventions are matched to the relatively few smokers in the preparation stage and will not assist the majority of smokers, who are in the precontemplation or contemplation stages. This study tested the hypothesis that stage-matched interventions increase movement through the stages relative to interventions not stage-matched. It also tested the hypothesis that the relative effectiveness of stage-matched interventions is greater for people in precontemplation or contemplation (stage-matched for TTM but not for control) than for people in preparation (where both intervention and control were stage-matched). A total of 2471 UK adult smokers were randomised to either control or TTM-based self-help intervention and followed up 12 months after beginning the programme. Content analysis of the intervention and control self-help interventions examined whether control interventions were action-oriented, meaning they emphasised the processes of change relevant for preparation and action. Participants in the TTM arm were slightly more likely to make a positive move in stage, but this was not significant. There was no evidence that the TTM-based intervention was more effective for participants in precontemplation or contemplation than for participants in preparation. There was no evidence that TTM-based interventions were effective in this trial. The control intervention advocated process use appropriate for all stages and was not action-orientated. Stage matching does not explain the modest effects of TTM-based interventions over control interventions observed in some trials. These effects may instead have occurred because TTM-based interventions were more intensive than control interventions.

Nortriptyline plus nicotine replacement versus placebo plus nicotine replacement for smoking cessation: pragmatic randomised controlled trial

Objective To test the efficacy of nortriptyline plus nicotine replacement therapy compared with placebo plus nicotine replacement therapy for smoking cessation. Design Pragmatic randomised controlled trial. Setting National Health Service stop smoking service clinics. Participants 901 people trying to stop smoking. Interventions Participants chose their nicotine replacement product, including combinations of nicotine replacement therapy, and received behavioural support. Nortriptyline was started one to two weeks before quit day, with the dose increased from 25 mg to 75 mg daily for eight weeks and reduced if not tolerated. Main outcome measures Primary outcome was prolonged confirmed abstinence at six months. Secondary outcomes were prolonged abstinence at 12 months, drug use, severity of side effects, nicotine withdrawal symptoms, and urges to smoke. Results 72 of 445 (16%) people using nortriptyline and 55 of 456 (12%) using placebo achieved prolonged abstinence at six months (relative risk 1.34, 95% confidence interval 0.97 to 1.86). At 12 months the corresponding values were 49 (11%) for nortriptyline and 40 (9%) for placebo (1.26, 0.84 to 1.87). 337 (79%) people in the nortriptyline arm and 325 (75%) in the placebo arm were taking combination treatment on quit day, median 75 mg per day in both groups. More people in the nortriptyline arm than in the placebo arm took lower doses. The nortriptyline arm had noticeably higher severity ratings for dry mouth and constipation than the placebo arm, with slightly higher ratings for sweating and feeling shaky. Both groups had similar urges to smoke, but nortriptyline reduced depression and anxiety. Overall, withdrawal symptom scores did not differ. Conclusions Nortriptyline and nicotine replacement therapy are both effective for smoking cessation but the effect of the combination is less than either alone and evidence is lacking that combination treatment is more effective than either alone. Trial registration Current Controlled Trials ISRCTN57852484.

A proof of concept randomised placebo controlled factorial trial to examine the efficacy of St John's wort for smoking cessation and chromium to prevent weight gain on smoking cessation.

BACKGROUND St Johns wort is an effective antidepressant that can reduce tobacco withdrawal symptoms, but it is not known whether it assists cessation. Chromium assists weight loss and might limit post cessation weight gain. METHODS In a factorial design, we randomised smokers stopping smoking to 900 mg St Johns wort (SJW) active or placebo and also randomised them to 400 microm chromium or placebo daily. Treatment started 2 weeks prior to quit day and continued for 14 weeks. Participants and researchers were blind to treatment allocation. All participants received weekly behavioural support. The primary endpoints were biochemically confirmed prolonged abstinence and mean weight gain in abstinent smokers 4 weeks after quitting. RESULTS 6/71 (8.5%) participants on active SJW and 9/72 (12.5%) on placebo achieved prolonged abstinence at 4 weeks, an odds ratio (OR) (95% confidence interval) of 0.65 (0.22-1.92). At 6 months, 3 (4.2%) SJW active and 6 (8.3%) SJW placebo participants were still abstinent, an OR of 0.49 (0.12-2.02). Among these participants, the mean difference in weight gain between active chromium and placebo was -0.8 1kg (-3.79 to 2.18) at 4 weeks and -3.88 kg (-12.13 to 4.38) at 6 months. CONCLUSIONS Taking together the absolute quit rates, the small difference between active and placebo, and lack of effects on withdrawal shows that SJW is ineffective for smoking cessation. Insufficient people stopped smoking to properly test the efficacy of chromium in preventing weight gain, but the point estimate indicates a potentially worthwhile benefit.