Is Tobacco Use Associated With Risk of Recurrence and Mortality Among People With TB?: A Systematic Review and Meta-Analysis.

BACKGROUND: Associations between tobacco use and poor TB treatment outcomes are well documented. However, for important outcomes such as TB recurrence or relapse and mortality during treatment, as well as for associations with smokeless tobacco (ST), the evidence is not summarized systematically. RESEARCH QUESTION: Is tobacco use associated with risk of poor treatment outcomes among people with TB? STUDY DESIGN AND METHODS: The MEDLINE, Embase, and Cumulative Index of Nursing and Allied Health Literature databases were searched on November 22, 2021. Epidemiologic studies reporting associations between tobacco use and at least one TB treatment outcome were eligible. Independent double-screening, extractions, and quality assessments were undertaken. Random effects meta-analyses were conducted for the two primary review outcomes (TB recurrence or relapse and mortality during treatment), and heterogeneity was explored using subgroups. Other outcomes were synthesized narratively. RESULTS: Our searches identified 1,249 records, of which 28 were included in the meta-analyses. Based on 15 studies, higher risk of TB recurrence or relapse was found with ever using tobacco vs never using tobacco (risk ratio [RR], 1.78; 95% CI, 1.31-2.43; I2 = 85%), current tobacco use vs no tobacco use (RR, 1.95; 95% CI, 1.59-2.40; I2 = 72%), and former tobacco use vs never using tobacco (RR, 1.84; 95% CI, 1.21-2.80; I2 = 4%); heterogeneity arose from differences in study quality, design, and participant characteristics. Thirty-eight studies were identified for mortality, of which 13 reported mortality during treatment. Ever tobacco use (RR, 1.55; 95% CI, 1.32-1.81; I2 = 0%) and current tobacco use (RR, 1.51; 95% CI, 1.09-2.10; I2 = 87%) significantly increased the likelihood of mortality during treatment among people with TB compared with never using tobacco and not currently using tobacco, respectively; heterogeneity was explained largely by differences in study design. Almost all studies in the meta-analyses scored high or moderate on quality assessments. Narrative synthesis showed that tobacco use was a risk factor for other unfavorable TB treatment outcomes, as previously documented. Evidence on ST was limited, but identified studies suggested an increased risk for poor outcomes with its use compared with not using it. INTERPRETATION: Tobacco use significantly increases the risk of TB recurrence or relapse and mortality during treatment among people with TB, highlighting the need to address tobacco use to improve TB outcomes. TRIAL REGISTRY: PROSPERO; No.: CRD42017060821; URL: https://www.crd.york.ac.uk/prospero/.

The global impact of tobacco control policies on smokeless tobacco use: a systematic review.

BACKGROUND: Smokeless tobacco, used by more than 300 million people globally, results in substantial morbidity and mortality. For smokeless tobacco control, many countries have adopted policies beyond the WHO Framework Convention on Tobacco Control, which has been instrumental in reducing smoking prevalence. The impact of these policies (within and outside the Framework Convention on Tobacco Control) on smokeless tobacco use remains unclear. We aimed to systematically review policies that are relevant to smokeless tobacco and its context and investigate their impact on smokeless tobacco use. METHODS: In this systematic review, we searched 11 electronic databases and grey literature between Jan 1, 2005, and Sept 20, 2021, in English and key south Asian languages, to summarise smokeless tobacco policies and their impact. Inclusion criteria were all types of studies on smokeless tobacco users that mentioned any smokeless tobacco relevant policies since 2005, except systematic reviews. Policies issued by organisations or private institutions were excluded as well as studies on e-cigarettes and Electronic Nicotine Delivery System except where harm reduction or switching were evaluated as a tobacco cessation strategy. Two reviewers independently screened articles, and data were extracted after standardisation. Quality of studies was appraised using the Effective Public Health Practice Project's Quality Assessment Tool. Outcomes for impact assessment included smokeless tobacco prevalence, uptake, cessation, and health effects. Due to substantial heterogeneity in the descriptions of policies and outcomes, data were descriptively and narratively synthesised. This systematic review was registered in PROSPERO (CRD42020191946). FINDINGS: 14 317 records were identified, of which 252 eligible studies were included as describing smokeless tobacco policies. 57 countries had policies targeting smokeless tobacco, of which 17 had policies outside the Framework Convention on Tobacco Control for smokeless tobacco (eg, spitting bans). 18 studies evaluated the impact, which were of variable quality (six strong, seven moderate, and five weak) and reported mainly on prevalence of smokeless tobacco use. The body of work evaluating policy initiatives based on the Framework Convention on Tobacco Control found that these initiatives were associated with reductions in smokeless tobacco prevalence of between 4·4% and 30·3% for taxation and 22·2% and 70·9% for multifaceted policies. Two studies evaluating the non-Framework policy of sales bans reported significant reductions in smokeless tobacco sale (6·4%) and use (combined sex 17·6%); one study, however, reported an increased trend in smokeless tobacco use in the youth after a total sales ban, likely due to cross-border smuggling. The one study reporting on cessation found a 13·3% increase in quit attempts in individuals exposed (47·5%) to Framework Convention on Tobacco Control policy: education, communication, training, and public awareness, compared with non-exposed (34·2%). INTERPRETATION: Many countries have implemented smokeless tobacco control policies, including those that extend beyond the Framework Convention on Tobacco Control. The available evidence suggests that taxation and multifaceted policy initiatives are associated with meaningful reductions in smokeless tobacco use. FUNDING: UK National Institute for Health Research.

A complex ePrescribing-based Anti-Microbial Stewardship (ePAMS+) intervention for hospitals combining technological and behavioural components: protocol for a feasibility trial.

BACKGROUND: Antimicrobial resistance is a leading global public health threat, with inappropriate use of antimicrobials in healthcare contributing to its development. Given this urgent need, we developed a complex ePrescribing-based Anti-Microbial Stewardship intervention (ePAMS+). METHODS: ePAMS+ includes educational and organisational behavioural elements, plus guideline-based clinical decision support to aid optimal antimicrobial use in hospital inpatients. ePAMS+ particularly focuses on prompt initiation of antimicrobials, followed by early review once test results are available to facilitate informed decision-making on stopping or switching where appropriate. A mixed-methods feasibility trial of ePAMS+ will take place in two NHS acute hospital care organisations. Qualitative staff interviews and observation of practice will respectively gather staff views on the technical component of ePAMS+ and information on their use of ePAMS+ in routine work. Focus groups will elicit staff and patient views on ePAMS+; one-to-one interviews will discuss antimicrobial stewardship with staff and will record patient experiences of receiving antibiotics and their thoughts on inappropriate prescribing. Qualitative data will be analysed thematically. Fidelity Index development will enable enactment of ePAMS+ to be measured objectively in a subsequent trial assessing the effectiveness of ePAMS+. Quantitative data collection will determine the feasibility of extracting data and deriving key summaries of antimicrobial prescribing; we will quantify variability in the primary outcome, number of antibiotic defined daily doses, to inform the future larger-scale trial design. DISCUSSION: This trial is essential to determine the feasibility of implementing the ePAMS+ intervention and measuring relevant outcomes, prior to evaluating its clinical and cost-effectiveness in a full scale hybrid cluster-randomised stepped-wedge clinical trial. Findings will be shared with study sites and with qualitative research participants and will be published in peer-reviewed journals and presented at academic conferences. TRIAL REGISTRATION: The qualitative and Fidelity Index research were approved by the Health and Research Authority and the North of Scotland Research Ethics Service (ref: 19/NS/0174). The feasibility trial and quantitative analysis (protocol v1.0, 15 December 2021) were approved by the London South East Research Ethics Committee (ref: 22/LO/0204) and registered with ISRCTN ( ISRCTN 13429325 ) on 24 March 2022.

Cost-utility of cytisine for smoking cessation over and above behavioural support in people with newly diagnosed pulmonary tuberculosis: an economic evaluation of a multicentre randomised controlled trial.

OBJECTIVES: To assess the cost-effectiveness of cytisine over and above brief behavioural support (BS) for smoking cessation among patients who are newly diagnosed with pulmonary tuberculosis (TB) in low-income and middle-income countries. DESIGN: An incremental cost-utility analysis was undertaken alongside a 12-month, double-blind, two-arm, individually randomised controlled trial from a public/voluntary healthcare sector perspective with the primary endpoint at 6 months post randomisation. SETTING: Seventeen subdistrict hospitals in Bangladesh and 15 secondary care hospitals in Pakistan. PARTICIPANTS: Adults (aged ≥18 years in Bangladesh and ≥15 years in Pakistan) with pulmonary TB diagnosed within the last 4 weeks who smoked tobacco daily (n=2472). INTERVENTIONS: Two brief BS sessions with a trained TB health worker were offered to all participants. Participants in the intervention arm (n=1239) were given cytisine (25-day course) while those in the control arm (n=1233) were given placebo. No significant difference was found between arms in 6-month abstinence. PRIMARY AND SECONDARY OUTCOME MEASURES: Costs of cytisine and BS sessions were estimated based on research team records. TB treatment costs were estimated based on TB registry records. Additional smoking cessation and healthcare costs and EQ-5D-5L data were collected at baseline, 6-month and 12-month follow-ups. Costs were presented in purchasing power parity (PPP) adjusted US dollars (US$). Quality-adjusted life years (QALYs) were derived from the EQ-5D-5L. Incremental total costs and incremental QALYs were estimated using regressions adjusting for respective baseline values and other baseline covariates. Uncertainty was assessed using bootstrapping. RESULTS: Mean total costs were PPP US$57.74 (95% CI 49.40 to 83.36) higher in the cytisine arm than in the placebo arm while the mean QALYs were -0.001 (95% CI -0.004 to 0.002) lower over 6 months. The cytisine arm was dominated by the placebo arm. CONCLUSIONS: Cytisine plus BS for smoking cessation among patients with TB was not cost-effective compared with placebo plus BS. TRIAL REGISTRATION NUMBER: ISRCTN43811467.

The effectiveness of behaviour change interventions delivered by non-dental health workers in promoting children's oral health: A systematic review and meta-analysis.

OBJECTIVES: Dental caries is the most common preventable childhood condition. Non-dental professionals and health workers are often well placed to support parents in adopting positive oral health behaviours for their children. The aim of this study was to determine the effectiveness of behaviour change interventions and their individual component behaviour change techniques (BCTs), that were delivered by non-dental professionals and health workers. METHODS: A systematic search of Ovid MEDLINE, PubMed, CINAHL, Cochrane Library, Web of Science, TRoPHI and PROQUEST from inception until March 2021 was conducted. Randomised controlled trials and quasi-experimental studies for improving oral health outcomes in children were included. Quality assessment was carried out using Cochrane Risk of Bias tool and ROBINS-I tool. Publication bias was assessed using funnel plots and Egger's regression intercept. Effect sizes were estimated as standardised mean difference (SMD) and odds ratio/risk ratio for proportions. Meta-analyses were performed for studies reporting mean decayed, missing, filled surfaces (dmfs) and mean decayed, missing, filled, teeth (dmft) indices. Behaviour change technique coding was performed using behaviour change technique taxonomy v1 (BCTTv1). RESULTS: Out of the 9,101 records retrieved, 36 studies were included with 28 showing a significant effect either in clinical and/or behavioural/knowledge outcomes. Most studies (n = 21) were of poor methodological quality. The pooled SMD for caries experience showed statistically significant result for caries prevention at surface level -0.15 (95% CI -0.25, -0.04) and at the tooth level -0.24 (95% CI -0.42, -0.07). In 28 effective interventions, 27 individual BCTs were identified and the most frequently used were: "Instructions on how to perform the behaviour" and "Information about health consequences". CONCLUSION: There is low quality of evidence suggesting non-dental professionals and health workers may help improve oral health outcomes for children. To confirm these findings, further high-quality studies incorporating a variety of BCTs in their interventions for adoption of good oral health behaviours are needed.

Effect of quitting smoking on health outcomes during treatment for tuberculosis: secondary analysis of the TB & Tobacco Trial.

BACKGROUND: Despite treatment, patients with tuberculosis (TB) who smoke have poorer outcomes compared with non-smokers. It is unknown, however, if quitting smoking during the 6 months of TB treatment improves TB outcomes. METHODS: The TB & Tobacco Trial was a double-blind, placebo-controlled randomised trial of cytisine for smoking cessation in 2472 patients with pulmonary TB in Bangladesh and Pakistan. In a secondary analysis, we investigated the hypothesis that smoking cessation improves health outcomes in patients during the TB treatment course. The outcomes included an eight-point TB clinical score, sputum conversion rates, chest X-ray grades, quality of life (EQ-5D-5L), TB cure plus treatment completion rates and relapse rates. These were compared between those who stopped smoking and those who did not, using regression analysis. RESULTS: We analysed the data of 2273 (92%) trial participants. Overall, 25% (577/2273) of participants stopped smoking. Compared with non-quitters, those who quit had better TB cure plus treatment completion rates (91% vs 80%, p<0.001) and lower TB relapse rates (6% vs 14%, p<0.001). Among quitters, a higher sputum conversion rate at week 9 (91% vs 87%, p=0.036), lower mean TB clinical scores (-0.20 points, 95% CI -0.31 to -0.08, p=0.001) and slightly better quality of life (mean EQ-5D-5L 0.86 vs 0.85, p=0.015) at 6 months were also observed. These differences, except quality of life, remained statistically significant after adjusting for baseline values, trial arm and TB treatment adherence rates. CONCLUSION: Patients with TB who stop smoking may have better outcomes than those who don't. Health professionals should support patients in stopping smoking.

Reporting Treatment Fidelity in Behavioral Tobacco Treatment Clinical Trials: Scoping Review and Measurement Recommendations.

INTRODUCTION: Adoption of rigorous standards for reporting treatment fidelity is essential for advancing discovery, validation, and implementation of behavioral treatments. Whereas the NIH Behavior Change Consortium (BCC) developed an assessment tool to assess the quality of reporting and monitoring of treatment fidelity across health behavior change interventions, it has not yet been applied specifically to treatment fidelity in behavioral tobacco treatment trials. AIMS AND METHODS: We conducted a scoping review of peer-reviewed, clinical trials of behavioral adult tobacco treatment interventions published in English between 2006 and 2018. Using the BCC treatment fidelity checklist, articles were coded for the presence or absence of various treatment fidelity strategies within each of 5 domains: Design, Training, Delivery, Receipt, and Enactment. Eligible articles (N = 755) were coded by two independent coders. RESULTS: The proportion of reporting strategies varied within the fidelity domains, ranging from 5.2% to 96.3% in Design, 1.9% to 24.9% in Training, 2.6% to 32.3% in Delivery, 5.2% to 44.3% in Receipt, and 6.7% to 43.2% in Enactment. The mean proportion of adherence to treatment fidelity strategies within each domain was: Design (68%), Training (14%), Delivery (15%), Receipt (16%), and Enactment (25%). Only 11 studies achieved ≥80% reporting across >1 fidelity domain. There was no evidence for improvement in fidelity reporting across the 13-year time frame from the initial BCC publication to the present. CONCLUSIONS: These findings illustrate the lack of consistency in fidelity reporting in tobacco treatment trials and underscore the challenges faced in evaluating rigor and reproducibility, as well as interpretation and dissemination of findings. Recommendations are made for improving fidelity reporting in tobacco treatment trials. IMPLICATIONS: The SRNT Treatment Research Network sponsored a scoping review to summarize the current state of reporting treatment fidelity and make recommendations for best practices in reporting fidelity in tobacco treatment trials. The review identified a lack of consistency in fidelity reporting, illustrating the challenges faced in evaluating rigor, and reproducibility, as well as interpretation and dissemination of findings.

Co-producing an intervention for tobacco cessation and improvement of oral health among diabetic patients in Bangladesh.

BACKGROUND: Tobacco consumption is a major risk factor for many diseases including diabetes and has deleterious effects on oral health. Diabetic patients are vulnerable to developing certain oral conditions. So far, no studies have attempted to co-develop a tobacco cessation intervention to be delivered in dental clinics for people with diabetes in Bangladesh. AIM: To co-produce a tobacco cessation intervention for people with diabetes for use in dental clinics in Bangladesh. OBJECTIVES: To assess: (1) tobacco use (patterns) and perceptions about receiving tobacco cessation support from dentists among people with diabetes attending the dental department of Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM) who smoke or use smokeless tobacco (ST) (2) current tobacco cessation support provision by the dentists of the dental department of BIRDEM (3) barriers and facilitators of delivering a tobacco cessation intervention at a dental clinic, and (4) to co-produce a tobacco cessation intervention with people with diabetes, and dentists to be used in the proposed context. METHODS: The study was undertaken in two stages in the dental department of BIRDEM, which is the largest diabetic hospital in Bangladesh. Stage 1 (July-August 2019) consisted of a cross-sectional survey among people with diabetes who use tobacco to address objective 1, and a survey and workshop with dentists working in BIRDEM, and consultations with patients to address objectives 2 and 3. Stage 2 (January 2020) consisted of consultations with patients attending BIRDEM, and a workshop with dentists to co-produce the intervention. RESULT: All survey participants (n = 35) were interested in receiving tobacco cessation support from their dentist. We identified important barriers and facilitators to deliver tobacco cessation intervention within dental services. Barriers reported by dentists included lack of a structured support system and lack of training. As a facilitator, we identified that dentists were willing to provide support and it would be feasible to deliver tobacco cessation intervention if properly designed and embedded in the routine functioning of the dental department of BIRDEM. Through the workshops and consultations at stage 2, a tobacco cessation intervention was co-developed. The intervention included elements of brief cessation advice (using a flipbook and a short video on the harmful effects of tobacco) and pharmacotherapy. CONCLUSION: Incorporation of tobacco cessation within dental care for people with diabetes was considered feasible and would provide a valuable opportunity to support this vulnerable group in quitting tobacco.

Supporting tobacco cessation in tuberculosis patients.

Tobacco is a key determinant of health inequalities, both across and within countries. 80% of tobacco users live in economically developing countries, which also face a huge tuberculosis (TB) burden. TB being an archetypal disease, affects low income groups, and has a higher proportion of smokers than the general population. The sub-group of TB patients who smoke disproportionately suffer from poorer outcomes, despite treatment. Behavioural interventions aimed at helping smokers quit by modifying their health beliefs and attitudes are highly successful in TB patients. However, integrating them in routine TB care is challenging, and requires a cultural shift at several levels, including individual, structural and organisational. We offer recommendations for policy, practice and research to address the dual burden of tobacco use and TB. Acting on these are vital towards achieving the United Nations (UN) Sustainable Development Goal (SDG) target of ending the TB epidemic by 2030.

Measuring fidelity to delivery of a new smoking cessation intervention integrated into routine tuberculosis care in Pakistan and Bangladesh: Contextual differences and opportunities.

INTRODUCTION: Tobacco smoking among tuberculosis (TB) patients leads to poorer treatment outcomes. Smoking cessation support should be integrated into routine TB care. We measured healthcare providers' fidelity to a smoking cessation intervention integrated into routine TB care, in Bangladesh and Pakistan. We aimed to understand the role of providers and settings in the implementation of behavior support (BS) messages for TB and smoking cessation. METHODS: The integrated BS intervention was implemented in TB clinics (24 public and 1 private). Cross-sectional data were collected on the fidelity of delivery of the BS intervention using a predefined fidelity index based on an existing validated method of measuring intervention fidelity. Audio-recordings of patient-provider BS sessions were coded using the fidelity index. Intervention fidelity was presented as the proportion of sessions that implemented BS messages. RESULTS: A total of 96 sessions were conducted, 37 in Bangladesh and 59 in Pakistan. In public settings, TB medication advice was offered in 91.9% (95% CI: 78.7- 97.2) of sessions in Bangladesh, and in 75.5% (95% CI: 62.4-85.1) of sessions in Pakistan; whilst it was offered in 83.3% (95% CI: 43.7-97.0) of sessions in the private setting in Pakistan. Patients' smoking status was assessed in 70.3% (95% CI: 54.2-82.5) of sessions in Bangladesh, and in 34.0% (95% CI: 22.7-47.4) of sessions in the public setting and in 66.7% (95% CI: 30.0-90.3) of sessions in the private setting in Pakistan. A quit date was set in 32.4% (95% CI: 19.6-48.5) of all sessions in Bangladesh, and in 33.3% (95% CI: 9.6-70.0) of all sessions in the public setting in Pakistan. CONCLUSIONS: Fidelity to the intended delivery of the intervention was found to be high for TB-related messages but not for smoking cessation messages. Clinic contexts may play a mediating role in health workers' opportunities to deliver the intervention as planned. TRIAL REGISTRATION: International Standard Randomized Clinical Trial Number (ISRCTN43811467). Registered 23 March 2016, https://doi.org/10.1186/ISRCTN43811467.

Predictors of Cigarette Smoking, Smokeless Tobacco Consumption, and Use of both forms in Adolescents in South Asia: A Secondary Analysis of the Global Youth Tobacco Surveys.

INTRODUCTION: Tobacco uptake in adolescents is associated with a range of predictors. We examined the predictors of cigarette smoking, smokeless tobacco (ST) consumption, and use of both ST and cigarettes among adolescents in four South Asian countries. METHODS: We analyzed the Global Youth Tobacco Surveys (GYTS) data for Bangladesh (2013), India (2009), Pakistan (2013), and Sri Lanka (2015), using multinomial regression to examine associations between several predictors and tobacco use. RESULTS: Data from 23 681 adolescents were analyzed. Overall, 82.8% of the study population were between 13 and 15 years and 52.7% were girls, 2% were cigarette smokers, 6.5% were ST users, and 1.1% used both ST and cigarettes, in the past 30 days. Exposure to smoking in public places was associated with past 30-day smoking (relative risk ratio [RRR] 5.59, 95% confidence intervals [CI] 4.28-7.28), ST use (RRR 2.07, 95% CI 1.84-2.32), and use of both ST and cigarettes (RRR 11.42, 95% CI 7.44-17.54). Exposure to tobacco use in electronic media and being offered free tobacco products were associated with all forms of tobacco use. Shopkeepers' refusal to sell cigarettes protected adolescents from smoking (RRR 0.47, 95% CI 0.36-0.63) and ST use (RRR 0.65, 95% CI 0.45-0.95). However, exposure to antitobacco mass media messages was not protective for any form of tobacco use. Adolescents taught at school about harmful effects of tobacco were less likely to use ST; no evidence of this association was observed for smoking. CONCLUSION: The associations between tobacco use and protobacco factors were strong, but the associations with antitobacco factors lacked strength and consistency in this study population. IMPLICATIONS: The predictors of adolescents using different tobacco products, crucial to inform and evaluate tobacco control efforts, are poorly understood. We investigated the associations between several environmental-level factors and cigarette smoking, ST consumption, and use of both forms among adolescents, whereas most of the previous studies focused on individual-level factors. Our study found strong associations between tobacco use and protobacco factors and lack of strength and consistency in associations between antitobacco factors and tobacco use in the study population. Our results indicate that the current tobacco control policies need strengthening to curb the tobacco epidemic in these countries.

Global impact of tobacco control policies on smokeless tobacco use: a systematic review protocol.

INTRODUCTION: Smokeless tobacco (ST) was consumed by 356 million people globally in 2017. Recent evidence shows that ST consumption is responsible for an estimated 652 494 all-cause deaths across the globe annually. The WHO Framework Convention on Tobacco Control (FCTC) was negotiated in 2003 and ratified in 2005 to implement effective tobacco control measures. While the policy measures enacted through various tobacco control laws have been effective in reducing the incidence and prevalence of smoking, the impact of ST-related policies (within WHO FCTC and beyond) on ST use is under-researched and not collated. METHODS AND ANALYSIS: A systematic review will be conducted to collate all available ST-related policies implemented across various countries and assess their impact on ST use. The following databases will be searched: Medline, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Scopus, EconLit, ISI Web of Science, Cochrane Library (CENTRAL), African Index Medicus, LILACS, Scientific Electronic Library Online, Index Medicus for the Eastern Mediterranean Region, Index Medicus for South-East Asia Region, Western Pacific Region Index Medicus and WHO Library Database, as well as Google search engine and country-specific government websites. All ST-related policy documents (FCTC and non-FCTC) will be included. Results will be limited to literature published since 2005 in English and regional languages (Bengali, Hindi and Urdu). Two reviewers will independently employ two-stage screening to determine inclusion. The Effective Public Health Practice Project's 'Quality Assessment Tool for Quantitative Studies' will be used to record ratings of quality and risk of bias among studies selected for inclusion. Data will be extracted using a standardised form. Meta-analysis and narrative synthesis will be used. ETHICS AND DISSEMINATION: Permission for ethics exemption of the review was obtained from the Centre for Chronic Disease Control's Institutional Ethics Committee, India (CCDC_IEC_06_2020; dated 16 April 2020). The results will be disseminated through publications in a peer-reviewed journal and will be presented in national and international conferences. PROSPERO REGISTRATION NUMBER: CRD42020191946.

Cytisine for smoking cessation in patients with tuberculosis: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial.

BACKGROUND: Smoking cessation is important in patients with tuberculosis because it can reduce the high rates of treatment failure and mortality. We aimed to assess the effectiveness and safety of cystine as a smoking cessation aid in patients with tuberculosis in Bangladesh and Pakistan. METHODS: We did a randomised, double-blind, placebo-controlled, trial at 32 health centres in Bangladesh and Pakistan. Eligible patients were adults (aged >18 years in Bangladesh; aged >15 years in Pakistan) with pulmonary tuberculosis diagnosed in the previous 4 weeks, who smoked tobacco on a daily basis and were willing to stop smoking. Patients were randomly assigned (1:1) to receive behavioural support plus either oral cytisine (9 mg on day 0, which was gradually reduced to 1·5 mg by day 25) or placebo for 25 days. Randomisation was done using pregenerated block randomisation lists, stratified by trial sites. Investigators, clinicians, and patients were masked to treatment allocation. The primary outcome was continuous abstinence at 6 months, defined as self-report (of not having used more than five cigarettes, bidis, a water pipe, or smokeless tobacco products since the quit date), confirmed biochemically by a breath carbon monoxide reading of less than 10 parts per million. Primary and safety analysis were done in the intention-to-treat population. This trial is registered with the International Standard Randomised Clinical Trial Registry, ISRCTN43811467, and enrolment is complete. FINDINGS: Between June 6, 2017, and April 30, 2018, 2472 patients (1527 patients from Bangladesh; 945 patients from Pakistan) were enrolled and randomly assigned to receive cytisine (n=1239) or placebo (n=1233). At 6 months, 401 (32·4%) participants in the cytisine group and 366 (29·7%) participants in the placebo group had achieved continuous abstinence (risk difference 2·68%, 95% CI -0·96 to 6·33; relative risk 1·09, 95% CI 0·97 to 1·23, p=0·114). 53 (4·3%) of 1239 participants in the cytisine group and 46 (3·7%) of 1233 participants in the placebo group reported serious adverse events (94 events in the cytisine group and 90 events in the placebo group), which included 91 deaths (49 in the cytisine group and 42 in the placebo group). None of the adverse events were attributed to the study medication. INTERPRETATION: Our findings do not support the addition of cytisine to brief behavioural support for the treatment of tobacco dependence in patients with tuberculosis. FUNDING: European Union Horizon 2020 and Health Data Research UK. TRANSLATIONS: For the Bengali and Urdu translations of the abstract see Supplementary Materials section.

Smoking prevalence among tuberculosis patients: A crosssectional study in Bangladesh and Pakistan.

INTRODUCTION: Smoking has a negative impact on TB outcomes. We estimated the proportion of TB patients who smoke and are willing to quit in two high TB burden countries, Bangladesh and Pakistan. METHODS: A cross-sectional survey was conducted among TB patients to assess their eligibility and recruit them to a smoking cessation randomized controlled trial. Adults diagnosed with TB were recruited from 32 health facilities in Bangladesh and Pakistan. Data on smoking behaviour and willingness to quit were collected and analysed. RESULTS: In total, 13934 TB patients completed the survey between June 2017 and April 2018. The prevalence of smoking in these TB patients was estimated to be 22.5% (95% CI: 21.8, 23.2). Moreover, the prevalence of smoking in TB patient population was 8% (RR=1.49; 95% CI: 7.1-8.9; p<0.01) and 8.3% (RR=1.24; 95% CI: 7.3-9.4; p<0.01) higher than smoking prevalence in the general population in Bangladesh and Pakistan, respectively. Among TB patients who smoke, 97.7% (95% CI: 97.2-98.2) were willing to quit. CONCLUSIONS: The estimated prevalence of smoking was higher in TB patients than the general population; however, a vast majority of TB patients who smoke were willing to quit.

Factors associated with dual use of waterpipe tobacco and cigarettes among adults in Pakistan.

BACKGROUND: Little is known about dual use of waterpipe tobacco and cigarettes, especially in countries where both are prevalent. AIMS: This study aimed to assess demographic correlates, patterns of use and quit behaviours of waterpipe users in Pakistan who also smoke cigarettes. METHODS: Data were taken from a randomized controlled trial in Pakistan that assessed smoking cessation in 510 adult waterpipe users, stratified on concurrent cigarette use. Logistic regression analysis was done to assess the association between waterpipe tobacco users who also smoke cigarettes (dual use) and their demographic characteristics, smoking history and quit behaviour. Unadjusted odds ratios (OR) and adjusted OR (ORa) and 95% confidence intervals (CI) were determined. RESULTS: Dual use was significantly associated with younger age (ORa = 0.36, 95% CI: 0.19-0.70) and middle-school educational level (11-15 years), versus no formal education, (ORa = 2.01, 95% CI: 1.15-3.50). Dual use was also associated with smoking less than all day versus all day (defined as continuously for several hours) (ORa = 2.71, 95%: CI 1.73-4.25) and younger age at starting smoking (ORa = 0.95, 95% CI: 0.93-0.98). No association was found between dual use and sex, marital status, duration of smoking, nicotine dependence or quit history. CONCLUSION: Waterpipe tobacco users who also smoke cigarettes differ from waterpipe-only users, particularly in demographic characteristics. More research is needed to explore the interaction between these two smoking behaviours. Health promotion and cessation interventions in Pakistan should consider tailoring their approach to account for the unique characteristics of dual waterpipe and cigarette users.

Identification of Policy Priorities to Address the Burden of Smokeless Tobacco in Pakistan: A Multimethod Analysis.

INTRODUCTION: We assessed the magnitude of smokeless tobacco (ST) use in Pakistan and identified policy gaps to help ascertain short-, medium-, and long-term priorities. We then elicited stakeholders' views as to which of these identified priorities are most important. METHODS: In a multimethod study, we: analyzed Global Tobacco Surveillance System data sets to estimate ST consumption and disease burden; conducted a documentary review to identify gaps in policies to control ST in comparison with smoking; elicited stakeholders' views in an interactive workshop to identify a set of policy options available to address ST burden in Pakistan; and ranked policy priorities using a postevent survey. RESULTS: Among all tobacco users in Pakistan (n = 24 million), one-third of men and two-thirds of women consume ST. In 2017, its use led to an estimated 18 711 deaths due to cancer and ischemic heart disease. Compared to smoking, policies to control ST lag behind significantly. Priority areas for ST policies included: banning ST sale to and by minors, advocacy campaigns, introduction of licensing, levying taxes on ST, and standardizing ST packaging. A clear commitment to close cooperation between state actors and stakeholder groups is needed to create a climate of support and information for effective policy making. CONCLUSIONS: Smokeless tobacco control in Pakistan should focus on four key policy instruments: legislation, education, fiscal policies, and quit support. More research into the effectiveness of such policies is also needed. IMPLICATIONS: A number of opportunities to improve ST regulation in Pakistan were identified. Among these, immediate priorities include banning ST sale to and by minors, mobilizing advocacy campaign, introduction of licensing through the 1958 Tobacco Vendors Act, levying taxes on ST, and standardizing ST packaging.

Measuring fidelity to behavioural support delivery for smoking cessation and its association with outcomes.

BACKGROUND AND AIMS: Behavioural support increases smoking cessation in clinical settings, but effect sizes differ among providers, due possibly to variations in delivery. This study evaluates a measure ('fidelity index') intended to capture fidelity to delivery of content- and interaction-based items of a behavioural support (BS) for smoking cessation and the association of fidelity with quit rates. METHODS: A fidelity index for scoring the adherence and quality domains of a specific BS intervention, '5As for quit', was developed by classifying the intervention components using the taxonomy of behaviour change techniques. The index was applied to code 154 BS sessions audiotaped among 18 chest clinics in Pakistan to assess their fidelity and explore reliability of coding. The association between intervention fidelity and successful quit achieved by the same providers in a previous study was explored using regression analysis. RESULTS: The index represented two domains: adherence to delivery of content-based activities of 5As (37 items) and quality of interaction-based activities (eight items). The intercoder reliability was good for content-based (average Krippendorff's α = 0.80) and moderate for interaction-based (average Krippendorff's α = 0.66) items. Approximately 70% (intraclass correlation coefficient: adherence scores = 0.72, quality scores = 0.71) of variation in BS delivery was contributed by providers, which increased to 97% (g-coefficient: adherence scores = 0.973, quality scores = 0.974) after accounting for other sources of variation. Higher quit rates were positively associated with average quality scores [risk ratio = 2.15; 95% confidence interval (CI) = 1.43-3.24], but negatively associated with average adherence scores (risk ratio = 0.55; 95% CI = 0.40-0.77) within services. CONCLUSIONS: The fidelity index is a reliable measure for quantifying intervention fidelity of delivering smoking cessation behavioural support. Recommended revisions of the fidelity index include incorporation of additional interaction-based items, such as the relational techniques used in motivational interviewing.

Health worker and patient views on implementation of smoking cessation in routine tuberculosis care.

Smoking worsens tuberculosis (TB) outcomes. Persons with TB who smoke can benefit from smoking cessation. We report findings of a multi-country qualitative process evaluation assessing barriers and facilitators to implementation of smoking cessation behaviour support in TB clinics in Bangladesh and Pakistan. We conducted semi-structured qualitative interviews at five case study clinics with 35 patients and 8 health workers over a period of 11 months (2017-2018) at different time points during the intervention implementation phase. Interviews were conducted by trained researchers in the native languages, audio-recorded, transcribed into English and analysed using a combined deductive-inductive approach guided by the Consolidated Framework for Implementation Research and Theoretical Domains Framework. All patients report willingness to quit smoking and recent quit attempts. Individuals' main motivations to quit are their health and the need to financially provide for a family. Behavioural regulation such as avoiding exposure to cigarettes and social influences from friends, family and colleagues are main themes of the interviews. Most male patients do not feel shy admitting to smoking, for the sole female patient interviewee stigma was an issue. Health workers report structural characteristics such as high workload and limited time per patient as primary barriers to offering behavioural support. Self-efficacy to discuss tobacco use with women varies by health worker. Systemic barriers to implementation such as staff workload and socio-cultural barriers to cessation like gender relations, stigma or social influences should be dealt with creatively to optimize the behaviour support for sustainability and scale-up.

The global prevalence of tobacco use in type 2 diabetes mellitus patients: A systematic review and meta-analysis.

BACKGROUND: A multi-layered association between tobacco use and type 2 diabetes mellitus (T2DM) is well established. However, global epidemiological patterns of tobacco use among T2DM patients are not well documented; this review thus aims to estimate the overall global burden of tobacco use in T2DM. METHODS: A systematic review of studies published from Jan 1, 1990 to October 5, 2017 was undertaken, comprising: a comprehensive literature search on multiple electronic databases; quality assessment of studies; data extraction for the primary (prevalence of tobacco use in T2DM patients) and secondary outcomes (patterns of tobacco use in T2DM patients); and a meta-analysis. The review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. A protocol for this review is available on PROSPERO (CRD42016038793). FINDINGS: 74 studies were included in the review, reporting data from 3.2 million participants across 33 countries. Global mean prevalence of tobacco use in T2DM was 20·81% (95% CI 18·93-22·76), and was higher in the WHO East Asia and Pacific and South Asia regions, compared to the Americas, Middle East and North Africa, Europe and Central Asia. In studies which compared prevalence of tobacco use in patients to non-patients, patients with T2DM were 26% less likely to use tobacco (pooled OR = 0·74 (CI 0·61-0·88). INTERPRETATION: Tobacco is used by one in five T2DM patients globally, but usage is less likely in patients than in non-patients. Global patterns of use demonstrated by this review have implications for both prevention and The understanding of diabetes burden, and the success of tobacco cessation strategies.