Biochemical Verification of Tobacco Use and Abstinence: 2019 Update.

BACKGROUND: The changing prevalence and patterns of tobacco use, the advent of novel nicotine delivery devices, and the development of new biomarkers prompted an update of the 2002 Society for Research on Nicotine and Tobacco (SRNT) report on whether and how to apply biomarker verification for tobacco use and abstinence. METHODS: The SRNT Treatment Research Network convened a group of investigators with expertise in tobacco biomarkers to update the recommendations of the 2002 SNRT Biochemical Verification Report. RESULTS: Biochemical verification of tobacco use and abstinence increases scientific rigor and is recommended in clinical trials of smoking cessation, when feasible. Sources, appropriate biospecimens, cutpoints, time of detection windows and analytic methods for carbon monoxide, cotinine (including over the counter tests), total nicotine equivalents, minor tobacco alkaloids, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol are reviewed, as well as biochemical approaches to distinguishing cigarette smoking from use of electronic nicotine delivery devices (ENDS). CONCLUSIONS: Recommendations are provided for whether and how to use biochemical verification of tobacco use and abstinence. Guidelines are provided on which biomarkers to use, which biospecimens to use, optimal cutpoints, time windows to detection, and methodology for biochemical verifications. Use of combinations of biomarkers is recommended for assessment of ENDS use. IMPLICATIONS: Biochemical verification increases scientific rigor, but there are drawbacks that need to be assessed to determine whether the benefits of biochemical verification outweigh the costs, including the cost of the assays, the feasibility of sample collection, the ability to draw clear conclusions based on the duration of abstinence, and the variability of the assay within the study population. This paper provides updated recommendations from the 2002 SRNT report on whether and how to use biochemical markers in determining tobacco use and abstinence.

'S'-shaped curve: modelling trends in smoking prevalence, uptake and cessation in Great Britain from 1973 to 2016.

BACKGROUND: It is believed that declines in smoking prevalence naturally slow over time as the smoking population 'hardens' and that progress has come primarily from reducing uptake rather than increasing cessation. To address these issues, we undertook the first formal attempt to model the trajectory of smoking prevalence and indices of uptake and cessation in Great Britain from 1973 to 2016. METHODS: Using data from the General Lifestyle Survey between 1973 and 2008, the Integrated Household Survey between 2009 and 2014 and the Annual Population Survey between 2015 and 2016, this study modelled year-on-year changes in smoking prevalence, ever-smoking in 18-24-year-olds as an index of uptake, and quit ratios as an index of cessation. RESULTS: For all three outcomes, changes over time were best fitted by what may be broadly characterised as 'S'-shaped curves: segmented functions characterised by initial rapid progress, a slowing or reversal, then renewed progress. Smoking prevalence in Great Britain showed a decelerating decline over time between 1973 and 2000, but then, after the introduction of the National 'Smoking Kills' tobacco control plan, the decline accelerated again and has remained nearly linear at -0.67 percentage points per year. Ever-smoking showed a decelerating decline which eventually ceased and began increasing around 1994 but then declined again after 2000. Quit ratios rose rapidly then slowed and then accelerated around 2000 and again more recently in 2013. CONCLUSION: Long-term trends in smoking prevalence, uptake and cessation have followed a broadly 'S'-shaped trend suggesting that they are responsive to major tobacco control initiatives. The decline in prevalence has resulted both from reductions in uptake and increases in cessation.

Relapse prevention interventions for smoking cessation.

BACKGROUND: A number of treatments can help smokers make a successful quit attempt, but many initially successful quitters relapse over time. Several interventions have been proposed to help prevent relapse. OBJECTIVES: To assess whether specific interventions for relapse prevention reduce the proportion of recent quitters who return to smoking. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group trials register, clinicaltrials.gov, and the ICTRP in February 2018 for studies mentioning relapse prevention or maintenance in their title, abstracts, or keywords. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials of relapse prevention interventions with a minimum follow-up of six months. We included smokers who quit on their own, were undergoing enforced abstinence, or were participating in treatment programmes. We included studies that compared relapse prevention interventions with a no intervention control, or that compared a cessation programme with additional relapse prevention components with a cessation programme alone. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 77 studies (67,285 participants), 15 of which are new to this update. We judged 21 studies to be at high risk of bias, 51 to be at unclear risk of bias, and five studies to be at low risk of bias. Forty-eight studies included abstainers, and 29 studies helped people to quit and then tested treatments to prevent relapse. Twenty-six studies focused on special populations who were abstinent because of pregnancy (18 studies), hospital admission (five studies), or military service (three studies). Most studies used behavioural interventions that tried to teach people skills to cope with the urge to smoke, or followed up with additional support. Some studies tested extended pharmacotherapy.We focused on results from those studies that randomised abstainers, as these are the best test of relapse prevention interventions. Of the 12 analyses we conducted in abstainers, three pharmacotherapy analyses showed benefits of the intervention: extended varenicline in assisted abstainers (2 studies, n = 1297, risk ratio (RR) 1.23, 95% confidence interval (CI) 1.08 to 1.41, I² = 82%; moderate certainty evidence), rimonabant in assisted abstainers (1 study, RR 1.29, 95% CI 1.08 to 1.55), and nicotine replacement therapy (NRT) in unaided abstainers (2 studies, n = 2261, RR 1.24, 95% Cl 1.04 to 1.47, I² = 56%). The remainder of analyses of pharmacotherapies in abstainers had wide confidence intervals consistent with both no effect and a statistically significant effect in favour of the intervention. These included NRT in hospital inpatients (2 studies, n = 1078, RR 1.23, 95% CI 0.94 to 1.60, I² = 0%), NRT in assisted abstainers (2 studies, n = 553, RR 1.04, 95% CI 0.77 to 1.40, I² = 0%; low certainty evidence), extended bupropion in assisted abstainers (6 studies, n = 1697, RR 1.15, 95% CI 0.98 to 1.35, I² = 0%; moderate certainty evidence), and bupropion plus NRT (2 studies, n = 243, RR 1.18, 95% CI 0.75 to 1.87, I² = 66%; low certainty evidence). Analyses of behavioural interventions in abstainers did not detect an effect. These included studies in abstinent pregnant and postpartum women at end of pregnancy (8 studies, n = 1523, RR 1.05, 95% CI 0.99 to 1.11, I² = 0%) and at postpartum follow-up (15 studies, n = 4606, RR 1.02, 95% CI 0.94 to 1.09, I² = 3%), studies in hospital inpatients (4 studies, n = 1300, RR 0.95, 95% CI 0.81 to 1.11, I² = 0%), and studies in assisted abstainers (10 studies, n = 5408, RR 0.99, 95% CI 0.87 to 1.13, I² = 56%; moderate certainty evidence) and unaided abstainers (5 studies, n = 3561, RR 1.06, 95% CI 0.96 to 1.16, I² = 1%) from the general population. AUTHORS' CONCLUSIONS: Behavioural interventions that teach people to recognise situations that are high risk for relapse along with strategies to cope with them provided no worthwhile benefit in preventing relapse in assisted abstainers, although unexplained statistical heterogeneity means we are only moderately certain of this. In people who have successfully quit smoking using pharmacotherapy, there were mixed results regarding extending pharmacotherapy for longer than is standard. Extended treatment with varenicline helped to prevent relapse; evidence for the effect estimate was of moderate certainty, limited by unexplained statistical heterogeneity. Moderate-certainty evidence, limited by imprecision, did not detect a benefit from extended treatment with bupropion, though confidence intervals mean we could not rule out a clinically important benefit at this stage. Low-certainty evidence, limited by imprecision, did not show a benefit of extended treatment with nicotine replacement therapy in preventing relapse in assisted abstainers. More research is needed in this area, especially as the evidence for extended nicotine replacement therapy in unassisted abstainers did suggest a benefit.

Relapse prevention interventions for smoking cessation.

BACKGROUND: A number of treatments can help smokers make a successful quit attempt, but many initially successful quitters relapse over time. Several interventions have been proposed to help prevent relapse. OBJECTIVES: To assess whether specific interventions for relapse prevention reduce the proportion of recent quitters who return to smoking. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group trials register, clinicaltrials.gov, and the ICTRP in May 2019 for studies mentioning relapse prevention or maintenance in their title, abstracts, or keywords. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials of relapse prevention interventions with a minimum follow-up of six months. We included smokers who quit on their own, were undergoing enforced abstinence, or were participating in treatment programmes. We included studies that compared relapse prevention interventions with a no intervention control, or that compared a cessation programme with additional relapse prevention components with a cessation programme alone. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 81 studies (69,094 participants), five of which are new to this update. We judged 22 studies to be at high risk of bias, 53 to be at unclear risk of bias, and six studies to be at low risk of bias. Fifty studies included abstainers, and 30 studies helped people to quit and then tested treatments to prevent relapse. Twenty-eight studies focused on special populations who were abstinent because of pregnancy (19 studies), hospital admission (six studies), or military service (three studies). Most studies used behavioural interventions that tried to teach people skills to cope with the urge to smoke, or followed up with additional support. Some studies tested extended pharmacotherapy. We focused on results from those studies that randomised abstainers, as these are the best test of relapse prevention interventions. Of the 12 analyses we conducted in abstainers, three pharmacotherapy analyses showed benefits of the intervention: extended varenicline in assisted abstainers (2 studies, n = 1297, risk ratio (RR) 1.23, 95% confidence interval (CI) 1.08 to 1.41, I2 = 82%; moderate-certainty evidence), rimonabant in assisted abstainers (1 study, RR 1.29, 95% CI 1.08 to 1.55), and nicotine replacement therapy (NRT) in unaided abstainers (2 studies, n = 2261, RR 1.24, 95% Cl 1.04 to 1.47, I2 = 56%). The remainder of analyses of pharmacotherapies in abstainers had wide confidence intervals consistent with both no effect and a statistically significant effect in favour of the intervention. These included NRT in hospital inpatients (2 studies, n = 1078, RR 1.23, 95% CI 0.94 to 1.60, I2 = 0%), NRT in assisted abstainers (2 studies, n = 553, RR 1.04, 95% CI 0.77 to 1.40, I2 = 0%; low-certainty evidence), extended bupropion in assisted abstainers (6 studies, n = 1697, RR 1.15, 95% CI 0.98 to 1.35, I2 = 0%; moderate-certainty evidence), and bupropion plus NRT (2 studies, n = 243, RR 1.18, 95% CI 0.75 to 1.87, I2 = 66%; low-certainty evidence). Analyses of behavioural interventions in abstainers did not detect an effect. These included studies in abstinent pregnant and postpartum women at the end of pregnancy (8 studies, n = 1523, RR 1.05, 95% CI 0.99 to 1.11, I2 = 0%) and at postpartum follow-up (15 studies, n = 4606, RR 1.02, 95% CI 0.94 to 1.09, I2 = 3%), studies in hospital inpatients (5 studies, n = 1385, RR 1.10, 95% CI 0.82 to 1.47, I2 = 58%), and studies in assisted abstainers (11 studies, n = 5523, RR 0.98, 95% CI 0.87 to 1.11, I2 = 52%; moderate-certainty evidence) and unaided abstainers (5 studies, n = 3561, RR 1.06, 95% CI 0.96 to 1.16, I2 = 1%) from the general population. AUTHORS' CONCLUSIONS: Behavioural interventions that teach people to recognise situations that are high risk for relapse along with strategies to cope with them provided no worthwhile benefit in preventing relapse in assisted abstainers, although unexplained statistical heterogeneity means we are only moderately certain of this. In people who have successfully quit smoking using pharmacotherapy, there were mixed results regarding extending pharmacotherapy for longer than is standard. Extended treatment with varenicline helped to prevent relapse; evidence for the effect estimate was of moderate certainty, limited by unexplained statistical heterogeneity. Moderate-certainty evidence, limited by imprecision, did not detect a benefit from extended treatment with bupropion, though confidence intervals mean we could not rule out a clinically important benefit at this stage. Low-certainty evidence, limited by imprecision, did not show a benefit of extended treatment with nicotine replacement therapy in preventing relapse in assisted abstainers. More research is needed in this area, especially as the evidence for extended nicotine replacement therapy in unassisted abstainers did suggest a benefit.

Smoking and Mortality in Eastern Europe: Results From the PrivMort Retrospective Cohort Study of 177 376 Individuals.

Background: The estimated prevalence of smoking and proportion of deaths due to tobacco in Eastern European countries are among the highest in the world. Existing estimates of mortality attributable to smoking in the region are mostly indirect. The aim of this analysis was to calculate the proportion of tobacco-attributed deaths in three Eastern European countries using individual level cohort data. Methods: The PrivMort project established a cohort of relatives of participants in population sample surveys in Russia, Belarus and Hungary. Survey participants provided data on smoking habits and vital statistics of their close relatives between 1982 and 2013. Population attributable risk fractions (PARF) in men (n = 99528) and women (n = 77848) aged 40-79 years were calculated from the prevalence rates of smoking and hazard ratios of mortality for smokers versus non-smokers. Trends in PARF over four 8-year time periods (1982-1989, 1990-1997, 1998-2005, and 2006-2013) were examined. Results: In men in the most recent period (2006-2013), the proportions of deaths attributable to tobacco were 23% in Russia, 22% in Belarus, and 22% in Hungary. The respective estimates in women were lower (2%, 2%, and 13%), possibly due to underestimation of smoking prevalence. PARF estimates have declined slightly since the early 1990s in men but increased in women. Conclusions: Consistently with existing indirect estimates, our results based on individual level cohort data suggest that over one fifth of all deaths in men aged 40-79 years are attributable to tobacco. While these proportions are lower in women, the increasing trend is a major concern. Implications: This is the first large scale, individual-level cohort study that estimated the mortality attributable to tobacco smoking directly in Eastern European population samples. The results confirm previous indirect estimates and show that more than 20% of all deaths in Eastern European men can be attributed to tobacco. The study also confirms the increasing trend in smoking-related deaths among women. These findings emphasize the importance of targeted policy interventions in Eastern European countries.

Variation in nicotine intake among U.S. cigarette smokers during the past 25 years: evidence from NHANES surveys.

OBJECTIVE: To estimate changes in nicotine intakes among U.S. cigarette smokers from 1988 to 2012 with the National Health and Nutrition Examination Survey (NHANES). METHODS: NHANES provides data on nationally representative samples of cigarette smokers from the civilian noninstitutionalized U.S. population. A total of 4,304 smokers aged 20 years and older were studied in NHANES III 1988-1994 and 7,095 were studied in the continuous NHANES 1999-2012. We examined serum cotinine concentrations, daily cigarette consumption, and estimated nicotine intake per cigarette, with adjustment for sex, age, racial/ethnic background, level of education, and body mass index. RESULTS: There was little overall change in nicotine intake from smoking cigarettes either in the U.S. population as a whole or in major racial/ethnic subgroups during the 25-year period from 1988. Serum cotinine averaged 223.7ng/mL (95% confidence interval [CI] = 216.1-231.3) in 1988-1994, which was not significantly different from the adjusted mean of 219.2ng/mL (95% CI = 214.1-224.4) in 1999-2012. During the same period, average daily cigarette consumption declined substantially, from 17.3 (95% CI = 16.5-18.0) in 1988-1994 to 12.3 (95% CI = 11.0-13.6) by 2012. Cotinine per cigarette smoked increased by some 42% between 1988-1994 and 2011-2012, from a geometric mean of 12.4 (95% CI = 11.7-13.1) to 17.6 (95% CI = 16.1-19.2). CONCLUSIONS: Reductions in cigarette smoking prevalence since the late 1980s, changes in cigarette product design, and the widespread introduction of smoke-free policies have not had a significant impact on nicotine intakes among U.S. smokers. Reductions in cigarette consumption have been offset by increased nicotine intake per cigarette smoked.

The effect of deep hypothermia on the human pulmonary circulation.

OBJECTIVE: Acute rises in pulmonary artery pressures following complex cardiac surgery are associated with high morbidity and mortality. We hypothesised that periods of deep hypothermia predispose to elevated pulmonary pressures upon rewarming. We investigated the effect of this hypothermic preconditioning on isolated human pulmonary arteries and isolated perfused lungs. METHODS: Isometric tension was measured in human pulmonary artery rings (n=24). We assessed the constriction and dilation of these arteries at 37 °C and 17 °C. Isolated perfused human lung models consisted of lobes ventilated via a bronchial cannula and perfused with Krebs via a pulmonary artery cannula. Bronchial and pulmonary artery pressures were recorded. We investigated the effect of temperature using a heat exchanger. RESULTS: Rewarming from 17 °C to 37 °C caused a 1.3 fold increase in resting tension (p<0.05). Arteries constricted 8.6 times greater to 30 nM KCl, constricted 17 times greater to 1 nM Endothelin-1 and dilated 30.3 times greater to 100 µM SNP at 37 °C than at 17 °C (p<0.005). No difference was observed in the responses of arteries originally maintained at 37 °C compared to those arteries maintained at 17 °C and rewarmed to 37 °C. Hypothermia blunted the increase in pulmonary artery pressures to stimulants such as potassium chloride as well as to H-R but did not precondition arteries to higher pulmonary artery pressures upon re-warming. CONCLUSIONS: Deep hypothermia reduces the responsiveness of human pulmonary arteries but does not, however, precondition an exaggerated response to vasoactive agents upon re-warming.

Secondhand Nicotine Absorption From E-Cigarette Vapor vs Tobacco Smoke in Children.

Importance: With the prevalence of e-cigarette use (vaping) increasing worldwide, there are concerns about children's exposure to secondhand vapor. Objective: To compare nicotine absorption among children who are (1) exposed to secondhand tobacco smoke only or (2) exposed to secondhand vapor only with (3) those exposed to neither. Design, Setting, and Participants: The US Continuous National Health and Nutrition Examination Survey (NHANES) is a repeat cross-sectional survey. Participants are interviewed in their homes and, several days after, visit a mobile examination center to provide biological specimens. This study uses data from a nationally representative sample of US households from 2017 to 2020. Participants were children aged 3 to 11 years with serum cotinine levels incompatible with current firsthand nicotine use (ie, <15 µg/L). The final analysis was conducted on January 9, 2024. Exposures: Reported exposure to secondhand smoke or vapor indoors in the past 7 days (only secondhand smoke, only secondhand vapor, or neither). Covariates included age, sex, ethnicity, family income, body weight, and height. Main Outcomes and Measures: The primary outcome was serum cotinine concentration, an objective biomarker of nicotine absorption. Geometric mean cotinine levels and 95% CIs were calculated using log-normal tobit regression, accounting for the complex survey design and weights. Results: The mean (SD) age of the 1777 children surveyed was 7.4 (2.6) years, 882 (49.6%) were female, and 531 (29.9%) had family incomes below the poverty level. Nicotine absorption, as indexed by serum cotinine level, was highest among children only exposed to secondhand smoke (0.494 µg/L µg/L; 95% CI, 0.386-0.633 µg/L), followed by those exposed only to secondhand vapor (0.081 µg/L; 95% CI, 0.048-0.137 µg/L), equating to 83.6% (95% CI, 71.5%-90.5%; P < .001) lower nicotine absorption. Among children with no reported secondhand exposure, the geometric mean cotinine level was 0.016 µg/L (95% CI, 0.013-0.021 µg/L), or 96.7% (95% CI, 95.6%-97.6%; P < .001) lower than for those with exposure to secondhand smoke. Results were similar after covariate adjustment. Conclusions and Relevance: In this cross-sectional study of US children, nicotine absorption was much lower in children who were exposed to secondhand vapor vs secondhand smoke, but higher than in those exposed to neither. These findings suggest that switching from smoking to vaping indoors may substantially reduce, but not eliminate, children's secondhand exposure to nicotine and other noxious substances.

Tobacco use in 3 billion individuals from 16 countries: an analysis of nationally representative cross-sectional household surveys.

BACKGROUND: Despite the high global burden of diseases caused by tobacco, valid and comparable prevalence data for patterns of adult tobacco use and factors influencing use are absent for many low-income and middle-income countries. We assess these patterns through analysis of data from the Global Adult Tobacco Survey (GATS). METHODS: Between Oct 1, 2008, and March 15, 2010, GATS used nationally representative household surveys with comparable methods to obtain relevant information from individuals aged 15 years or older in 14 low-income and middle-income countries (Bangladesh, Brazil, China, Egypt, India, Mexico, Philippines, Poland, Russia, Thailand, Turkey, Ukraine, Uruguay, and Vietnam). We compared weighted point estimates and 95% CIs of tobacco use between these 14 countries and with data from the 2008 UK General Lifestyle Survey and the 2006-07 US Tobacco Use Supplement to the Current Population Survey. All these surveys had cross-sectional study designs. FINDINGS: In countries participating in GATS, 48·6% (95% CI 47·6-49·6) of men and 11·3% (10·7-12·0) of women were tobacco users. 40·7% of men (ranging from 21·6% in Brazil to 60·2% in Russia) and 5·0% of women (0·5% in Egypt to 24·4% in Poland) in GATS countries smoked a tobacco product. Manufactured cigarettes were favoured by most smokers (82%) overall, but smokeless tobacco and bidis were commonly used in India and Bangladesh. For individuals who had ever smoked daily, women aged 55-64 years at the time of the survey began smoking at an older age than did equivalently aged men in most GATS countries. However, those individuals who had ever smoked daily and were aged 25-34-years when surveyed started to do so at much the same age in both sexes. Quit ratios were very low (<20% overall) in China, India, Russia, Egypt, and Bangladesh. INTERPRETATION: The first wave of GATS showed high rates of smoking in men, early initiation of smoking in women, and low quit ratios, reinforcing the view that efforts to prevent initiation and promote cessation of tobacco use are needed to reduce associated morbidity and mortality. FUNDING: Bloomberg Philanthropies' Initiative to Reduce Tobacco Use, Bill and Melinda Gates Foundation, Brazilian and Indian Governments.

Dispelling myths about gender differences in smoking cessation: population data from the USA, Canada and Britain.

OBJECTIVES: Based mainly on findings from clinical settings, it has been claimed that women are less likely than men to quit smoking successfully. If true, this would have important implications for tobacco control interventions. The authors aimed to test this possibility using data from general population surveys. METHODS: The authors used data from major national surveys conducted in 2006-2007 in the USA (Tobacco Use Supplement to the Current Population Survey), Canada (Canadian Tobacco Use Monitoring Survey) and the UK (General Household Survey) to estimate rates of smoking cessation by age in men and women. RESULTS: The authors found a pattern of gender differences in smoking cessation which was consistent across countries. Below age 50, women were more likely to have given up smoking completely than men, while among older age groups, men were more likely to have quit than women. Across all age groups, there was relatively little difference in cessation between the sexes. CONCLUSIONS: Conclusions about gender differences in smoking cessation should be based on evidence from the general population rather than from atypical clinical samples. This study has found convincing evidence that men in general are not more likely to quit smoking successfully than women.

Relapse prevention interventions for smoking cessation.

BACKGROUND: A number of treatments can help smokers make a successful quit attempt, but many initially successful quitters relapse over time. Several interventions have been proposed to help prevent relapse. OBJECTIVES: To assess whether specific interventions for relapse prevention reduce the proportion of recent quitters who return to smoking. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group trials register in May 2013 for studies mentioning relapse prevention or maintenance in title, abstracts or keywords. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials of relapse prevention interventions with a minimum follow-up of six months. We included smokers who quit on their own, were undergoing enforced abstinence, or were participating in treatment programmes. We included trials that compared relapse prevention interventions with a no intervention control, or that compared a cessation programme with additional relapse prevention components with a cessation programme alone. DATA COLLECTION AND ANALYSIS: Studies were screened and data extracted by one review author, and checked by a second. Disagreements were resolved by discussion or by referral to a third review author. MAIN RESULTS: Sixty-three studies met inclusion criteria but were heterogeneous in terms of populations and interventions. We considered 41 studies that randomly assigned abstainers separately from studies that randomly assigned participants before their quit date.Upon looking at studies of behavioural interventions that randomly assigned abstainers, we detected no benefit of brief and 'skills-based' relapse prevention methods for women who had quit smoking because of pregnancy, or for smokers undergoing a period of enforced abstinence during hospitalisation or military training. We also failed to detect significant effects of behavioural interventions in trials in unselected groups of smokers who had quit on their own or through a formal programme. Amongst trials randomly assigning smokers before their quit date and evaluating the effects of additional relapse prevention components, we found no evidence of benefit of behavioural interventions or combined behavioural and pharmacotherapeutic interventions in any subgroup. Overall, providing training in skills thought to be needed for relapse avoidance did not reduce relapse, but most studies did not use experimental designs best suited to the task and had limited power to detect expected small differences between interventions. For pharmacological interventions, extended treatment with varenicline significantly reduced relapse in one trial (risk ratio (RR) 1.18, 95% confidence interval (CI) 1.03 to 1.36). Pooling of six studies of extended treatment with bupropion failed to detect a significant effect (RR 1.15, 95% CI 0.98 to 1.35). Two small trials of oral nicotine replacement treatment (NRT) failed to detect an effect, but treatment compliance was low, and in two other trials of oral NRT in which short-term abstainers were randomly assigned, a significant effect of intervention was noted. AUTHORS' CONCLUSIONS: At the moment, there is insufficient evidence to support the use of any specific behavioural intervention to help smokers who have successfully quit for a short time to avoid relapse. The verdict is strongest for interventions focused on identifying and resolving tempting situations, as most studies were concerned with these. Little research is available regarding other behavioural approaches.Extended treatment with varenicline may prevent relapse. Extended treatment with bupropion is unlikely to have a clinically important effect. Studies of extended treatment with nicotine replacement are needed.

Effects of reduced-risk nicotine-delivery products on smoking prevalence and cigarette sales: an observational study.

Background: It is not currently clear what impact alternative nicotine-delivery products (electronic cigarettes, heated tobacco products and snus) have on smoking rates and cigarette sales. Objective: To assess whether access to these products promotes smoking in the population. Design and data sources: We examined associations of alternative nicotine product use and sales with smoking rates and cigarette sales overall, and in different age and socioeconomic groups, and compared smoking prevalence over time in countries with contrasting regulations of these products. For electronic cigarettes, we examined data from countries with historically similar smoking trajectories but differing current electronic cigarette regulations (United Kingdom and United States of America vs. Australia, where sales of nicotine-containing electronic cigarettes are banned); for heated tobacco, we used data from countries with state tobacco monopolies, where cigarette and heated tobacco sales data are available (Japan, South Korea), and for snus we used data from Sweden. Analysis methods: We pre-specified dynamic time series analyses to explore associations between use and sales of alternative nicotine-delivery products and smoking prevalence and cigarette sales, and time series analyses to compare trends of smoking prevalence in countries with different nicotine product policies. Results: Because of data and analysis limitations (see below), results are only tentative and need to be interpreted with caution. Only a few findings reached statistical significance and for most results the Bayes factor indicated inconclusive evidence. We did not find an association between rates of smoking and rates of the use of alternative nicotine products. The increase in heated tobacco product sales in Japan was accompanied by a decrease in cigarette sales. The decline in smoking prevalence seems to have been slower in Australia than in the United Kingdom overall, and slower than in both the United Kingdom and the United States of America among young people and also in lower socioeconomic groups. The decline in cigarette sales has also accelerated faster in the United Kingdom than in Australia. Limitations: Most of the available data had insufficient data points for robust time series analyses. The assumption of our statistical approach that causal interactions are more likely to be detected when longer-term changes are screened out may not apply for short time series and in product interaction scenarios, where short-term fluctuations can be caused by, for example, fluctuations in prosperity or product supplies. In addition, due to dual use, prevalence figures for smoking and alternative product use overlap. The ecological study design limits the causal inferences that can be made. Longer time periods are needed for any effects of exclusive use of the new products on smoking prevalence to emerge. Conclusions: We detected some indications that alternative nicotine products are competing with cigarettes rather than promoting smoking and that regulations that allow their sales are associated with a reduction rather than an increase of smoking, but the findings are inconclusive because of insufficient data points and issues with the assumptions of the pre-specified statistical analyses. Future work: As further prevalence and sales data emerge the analyses will become more informative. Accessing sales figures in particular is the current research priority. Study registration: The project is registered on Open Science Framework https://osf.io/bd3ah. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR129968) and will be published in full in Public Health Research; Vol. 11, No. 7. See the NIHR Journals Library website for further project information.

Alternative nicotine-delivery products are now available which are much less hazardous than cigarettes. These include electronic cigarettes (which contain no tobacco), Swedish snus (oral tobacco with low levels of cancer-causing chemicals) and heated tobacco products. There is concern that these products attract young people to smoking and discourage smokers from quitting (i.e. increase smoking), but it is also possible that they help smokers quit and steer young people who find nicotine attractive away from smoking, or that they have no effect on smoking. To clarify which of these end results is likely, we looked at data on smoking and on the use of these alternative products over time, and also compared data on smoking from countries that have similar tobacco control history, but that either allow (i.e. United Kingdom and United States of America) or ban the sale of electronic cigarettes (i.e. Australia). As the sale of heated tobacco products increased in Japan, sales of cigarettes seem to have gone down, suggesting that this product is competing with cigarettes rather than encouraging their use. We also found that the drop in smoking may have been slower in Australia than in the United Kingdom. For young people and those on low income specifically, the reduction in smoking was slower in Australia than in both the United Kingdom and United States of America. Allowing alternative nicotine products to be sold seems to have been linked with lowered rather than increased rates of smoking. Our findings, however, are uncertain because only limited data were available. Clearer conclusions will become possible as more data on the use and especially on the sales of alternative nicotine products are collected.

Impact of smoke-free legislation on children's exposure to secondhand smoke: cotinine data from the Health Survey for England.

OBJECTIVE: To examine the impact of the ban on smoking in enclosed public places implemented in England in July 2007 on children's exposure to secondhand tobacco smoke. DESIGN: Repeated cross-sectional surveys of the general population in England. SETTING: The Health Survey for England. PARTICIPANTS: Confirmed non-smoking children aged 4-15 with measured saliva cotinine participating in surveys from 1998 to 2008, a total of 10,825 children across years. MAIN OUTCOME MEASURES: The proportion of children living in homes reported to be smoke-free; the proportion of children with undetectable concentrations of cotinine; geometric mean cotinine as an objective indicator of overall exposure. RESULTS: Significantly more children with smoking parents lived in smoke-free homes in 2008 (48.1%, 95% CI 43.0% to 53.1%) than in either 2006 (35.5%, 95% CI 29.7% to 41.7%) or the first 6 months of 2007, immediately before the ban came into effect (30.5%, 95% CI 19.7% to 43.9%). A total of 41.1% (95% CI 38.9% to 43.4%) of children had undetectable cotinine in 2008, up from 34.0% (95% CI 30.8% to 37.3%) in 2006. Geometric mean cotinine in all children combined was 0.21 ng/ml (95% CI 0.20 to 0.23) in 2008, slightly lower than in 2006, 0.24 ng/ml (95% CI 0.21 to 0.26). CONCLUSIONS: Predictions that the 2007 legislative ban on smoking in enclosed public places would adversely affect children's exposure to tobacco smoke were not confirmed. While overall exposure in children has not been greatly affected by the ban, the trend towards the adoption of smoke-free homes by parents who themselves smoke has received fresh impetus.

High prevalence of hemoglobin disorders and glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Republic of Guinea (West Africa).

Reliable and accurate epidemiological data is a prerequisite for a cost effective screening program for inherited disorders, which however, is lacking in a number of developing countries. Here we report the first detailed population study in the Republic of Guinea, a sub-Saharan West African country, designed to assess the frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency and hemoglobinopathies, including screening for thalassemia. Peripheral blood samples from 187 Guinean adults were screened for hemoglobin (Hb) variants by standard hematological methods. One hundred and ten samples from males were screened for G6PD deficiency by the fluorescent spot test. Molecular analysis was performed for the most common α-thalassemia (α-thal) deletions, ß-globin gene mutations, G6PD variants B (376A), A (376G), A- (376G/202A) and Betica (376G/968C), using polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) or sequencing. Of the 187 subjects screened, 36 were heterozygous for Hb S [ß6(A3)Glu→Val, GAG>GTG] (allele frequency 9.62%). Sixty-four subjects were heterozygous and seven were homozygous for the -α(3.7) kb deletion (allele frequency 20.85%). ß-Thalassemia alleles were detected in five subjects, four with the -29 (A>G) mutation (allele frequency 1.07%) and one with codon 15 (TGG>TAG) (allele frequency 0.96%). The G6PD A- and G6PD Betica deficient variants were highly prevalent with a frequency of 5.7 and 3.3%, respectively. While we did not test for ferritin levels or α(0)-thal, four females (5.2%) had red cell indices strongly suggestive of iron deficient anemia: Hb <9.7 g/dL; MCH <19.3 pg; MCV <68.2; MCHC <31.6 g/dl; RDW >19.8%. Our results are consistent with high frequency of alleles such as Hb S, α-thal and G6PD deficient alleles associated with malaria resistance. Finding a 9.6% Hb S allele frequency supports the notion for a proficient neonatal screening to identify the sickle cell patients, who might benefit from early prophylactic treatment for infections. The incidence of significant iron deficient anemia in women is lower than expected in an under developed country.

Children's exposure to second-hand smoke 10 years on from smoke-free legislation in England: Cotinine data from the Health Survey for England 1998-2018.

BACKGROUND: We aimed to investigate trends in children's exposure to second-hand tobacco smoke in England from 1998 to 2018. METHODS: We used twenty-one years of data from the Health Survey for England, a yearly repeated cross-sectional population study. A total of 49,460 children participated between 1998 and 2018, of whom 17,463 were biochemically confirmed non-smokers aged 4-15. We examined changes in (i) the proportion of children living in reported smoke-free homes and (ii) second-hand smoke uptake, measured quantitatively using saliva cotinine concentration. FINDINGS: The percentage of children living in a home reported to be smoke-free increased from 63.0% (95% CI 60.5%-65.2%) in 1998 to 93.3% (91.8%-94.6%) in 2018. This increase was most pronounced among children with a smoker parent, rising from 17.1% (14.7%-19.8%) to 75.9% (70.8%-80.4%). Segmented regression showed that the rate of adoption of smoke-free homes accelerated leading up to the 2007 ban on smoking in public places, growing most rapidly in the four years after its entry into law. Between 1998 and 2018, there was a ten-fold decline in geometric mean cotinine among non-smoking children, from 0.50 ng/ml (0.46-0.56) to 0.05 ng/ml (0.04-0.06). A total of 65.0% (61.2%-68.6%) of children had undetectable cotinine in 2018, up from 14.3% (12.7%-16.0%) in 1998. Children living in rented accommodation were more exposed than those from owner-occupied households, but they experienced similar relative declines across years. INTERPRETATION: Cotinine data show that children's exposure to second-hand smoke has fallen by some 90% since 1998, with an apparent acceleration in adoption of smoke-free homes since the 2007 ban on smoking in public places. A norm has emerged that sees smoking in the home as inappropriate, almost universally where parents are non-smokers, but also increasingly among smoking parents. FUNDING: Public Health England, now the Office for Health Improvement and Disparities, and Cancer Research UK.

'The smoking toolkit study': a national study of smoking and smoking cessation in England.

BACKGROUND: Up-to-date data tracking of national smoking patterns and cessation-related behaviour is required to evaluate and inform tobacco control strategies. The Smoking Toolkit Study (STS) was designed for this role. This paper describes the methodology of the STS and examines as far as possible the representativeness of the samples. METHODS: The STS consists of monthly, cross sectional household interviews of adults aged 16 and over in England with smokers and recent ex-smokers in each monthly wave followed up by postal questionnaires three and six months later. Between November 2006 and December 2010 the baseline survey was completed by 90,568 participants. STS demographic, prevalence and cigarette consumption estimates are compared with those from the Health Survey for England (HSE) and the General Lifestyle Survey (GLF) for 2007-2009. RESULTS: Smoking prevalence estimates of all the surveys were similar from 2008 onwards (e.g 2008 STS=22.0%, 95% C.I.=21.4% to 22.6%, HSE=21.7%, 95% C.I.=20.9% to 22.6%, GLF=20.8%, 95% C.I.=19.7% to 21.9%), although there was heterogeneity in 2007 (chi-square=50.30, p<0.001). Some differences were observed across surveys within sociodemographic sub-groups, although largely in 2007. Cigarette consumption was virtually identical in all surveys and years. CONCLUSION: There is reason to believe that the STS findings (see http://www.smokinginengland.info) are generalisable to the adult population of England.

Dependence on nicotine in US high school students in the context of changing patterns of tobacco product use.

BACKGROUND AND AIM: There have been substantial recent changes in youth tobacco product use in the United States-including, notably, a rapid increase in use of e-cigarettes. It is not known whether, and if so how far, these changes are reflected in levels of nicotine dependence. This study used data from a large, nationally representative sample of US adolescents to (i) estimate the annual prevalence of nicotine dependence in relation to current use of tobacco products, (ii) describe trends in dependence over time and (iii) evaluate whether the increase in youth use of tobacco products has been paralleled by a similar increase in the population burden of nicotine dependence. DESIGN: Secondary analysis of National Youth Tobacco Surveys conducted annually, 2012-19. SETTING: United States. PARTICIPANTS: A total of 86 902 high school students. MEASUREMENTS: Prevalence of (i) strong cravings to use tobacco in the past 30 days and (ii) wanting to use nicotine products within 30 minutes of waking, in relation to type of product used (cigarettes, other combustible tobacco, smokeless tobacco, e-cigarettes). FINDINGS: Between 2012 and 2019 there was a marked decline in past 30-day cigarette smoking and a surge in use of e-cigarettes. Different products were associated with differing levels of nicotine dependence, with cigarettes characterized by highest dependence (strong craving 42.3%; wanting to use within 30 minutes 16.8% among exclusive users in 2019) and e-cigarettes in otherwise tobacco-naive students by low dependence (16.1 and 8.8% respectively in 2019). The overall 33.8% increase in population use of nicotine products between 2012 and 2019 (from 23.2 to 31.2%) was not accompanied by an equivalent increase in overall population burden of dependence {percentage reporting craving 10.9% [95% confidence interval (CI) = 9.8-12.2%] in 2012 and 9.5% (95% CI = 7.5-12.0%) in 2019; wanting to use within 30 minutes 4.7% (95% CI = 4.0-5.5%) in 2012, 5.4% (95% CI = 4.0-7.2%) in 2019}. CONCLUSIONS: Among US high school students, increases in the prevalence of nicotine product use from 2012 to 2019 do not appear to have been accompanied by a similar increase in the population burden of nicotine dependence. This may be at least partly attributable to a shift in the most common product of choice from cigarettes (on which users are most dependent) to e-cigarettes (on which users are least dependent).

England SimSmoke: the impact of nicotine vaping on smoking prevalence and smoking-attributable deaths in England.

BACKGROUND AND AIMS: Whereas the use of nicotine vaping products (NVPs) is widespread, their impact on smoking prevalence is controversial. This study considered the potential impact of NVPs on smoking prevalence in England. DESIGN: Indirect simulation model. The England SimSmoke model is validated through 2012, before NVP use became more widely used by smokers. Because information on NVP-related transitions is limited, an indirect method is used; the difference in observed smoking prevalence (reflecting NVPs) is compared with a 2012-2019 counterfactual No-NVP scenario (without NVPs) to estimate the impact of NVPs on smoking and smoking-attributable deaths. SETTING: England, 2000-2019. PARTICIPANTS: Nationally representative sample of population. MEASUREMENTS: England's population, mortality rates and smoking prevalence estimates from three national surveys and tobacco control policies. FINDINGS: Between 2000 and 2012, SimSmoke projected a decline in age 18+ smoking prevalence of 23.5% in men and 27.0% in women. These projections, as well as those by specific age groups, were generally consistent with findings from the three national surveys. Comparing 2012-2019 relative reduction in age 18+ prevalence from the Annual Population Survey (males, 27.5%) with the model-predicted No-NVP reduction (males, 7.3%), the implied NVP-attributable relative reduction in adult smoking prevalence was 20.2% (95% CI, 18.8%-22.0%) for males and 20.4% (18.7%-22.2%) for females. The NVP-attributable reduction was 27.2% (22.8%-31.6%) for males and 31.7% (27.4%-36.5%) for females ages 18-24 and 18.6% (15.2%-21.8%) for males and 15.0% (11.1%-18.8%) for females ages 25-34, with similar reductions for ages 35+. The implied reduction in smoking prevalence between 2012 and 2019 equates to 165 660 (132 453-199 501) averted deaths by 2052. Other surveys yielded smaller, but relatively consistent results. CONCLUSIONS: An indirect method of simulation modelling indicates that substantial reductions in smoking prevalence occurred in England from 2012-2019 coinciding with the growth in nicotine vaping product use.

Surgical aortic valve replacement in the era of transcatheter aortic valve implantation: a review of the UK national database.

OBJECTIVES: To date the reported outcomes of surgical aortic valve replacement (SAVR) are mainly in the settings of trials comparing it with evolving transcatheter aortic valve implantation. We set out to examine characteristics and outcomes in people who underwent SAVR reflecting a national cohort and therefore 'real-world' practice. DESIGN: Retrospective analysis of prospectively collected data of consecutive people who underwent SAVR with or without coronary artery bypass graft (CABG) surgery between April 2013 and March 2018 in the UK. This included elective, urgent and emergency operations. Participants' demographics, preoperative risk factors, operative data, in-hospital mortality, postoperative complications and effect of the addition of CABG to SAVR were analysed. SETTING: 27 (90%) tertiary cardiac surgical centres in the UK submitted their data for analysis. PARTICIPANTS: 31 277 people with AVR were identified. 19 670 (62.9%) had only SAVR and 11 607 (37.1%) had AVR+CABG. RESULTS: In-hospital mortality for isolated SAVR was 1.9% (95% CI 1.6% to 2.1%) and was 2.4% for AVR+CABG. Mortality by age category for SAVR only were: <60 years=2.0%, 60-75 years=1.5%, >75 years=2.2%. For SAVR+CABG these were; 2.2%, 1.8% and 3.1%. For different categories of EuroSCORE, mortality for SAVR in low risk people was 1.3%, in intermediate risk 1% and for high risk 3.9%. 74.3% of the operations were elective, 24% urgent and 1.7% emergency/salvage. The incidences of resternotomy for bleeding and stroke were 3.9% and 1.1%, respectively. Multivariable analyses provided no evidence that concomitant CABG influenced outcome. However, urgency of the operation, poor ventricular function, higher EuroSCORE and longer cross clamp and cardiopulmonary bypass times adversely affected outcomes. CONCLUSIONS: Surgical SAVR±CABG has low mortality risk and a low level of complications in the UK in people of all ages and risk factors. These results should inform consideration of treatment options in people with aortic valve disease.

CYP1A1 MSPI (T6235C) gene polymorphism is associated with mortality in acute coronary syndrome patients.

1. The CYP1A1 T6235C polymorphism (rs4646903) gene polymorphism has been linked to the development of coronary heart disease and cigarette smoking-related lung cancer. The present study investigated associations between survival in acute coronary syndromes (ACS), smoking and the CYP1A1 T6235C polymorphism. 2. Patients with ACS (n = 1251) were genotyped for the CYP1A1 T6235C polymorphism. Patients had a mean age of 67.0 years, 69.8% were male and follow up occurred over a median of 1.9 years. 3. Overall genotype frequencies were CC 2.2%, TC 21.7% and TT 76.1%. The CC genotype was associated with baseline characteristics of a higher incidence of Type 2 diabetes (P = 0.017), elevated body mass index (P = 0.001) and younger age (P = 0.045). Patients with the CC genotype had significantly worse survival than TT/TC patients (P = 0.014), independent of ethnicity and established clinical risk factors. When survival was stratified by smoking history, the T6235C genotype was particularly associated with mortality in past or current smokers (mortality 23.5 vs 9.4% in CC and TT/TC patients, respectively; P = 0.019) compared with those who had never smoked (mortality 11.1 vs 11.5% in CC and TT/TC patients, respectively; P = 0.853). 4. The results indicate that the homozygous CYP1A1 6235C genotype is associated with greater mortality following the onset of ACS, independent of ethnicity and clinical risk factors, but related to smoking history.