Conducting tobacco control surveys among schoolchildren in Bangladesh, India and Pakistan: A feasibility study.

Most of the world's 300 million smokeless tobacco (ST) users live in South Asia but ST policies for that region are poorly researched, developed and implemented. Longitudinal studies to understand the uptake and use of ST and smoking, and influences on these, such as health promotion strategies, are lacking. We planned to conduct longitudinal surveys among secondary school students in three countries with the highest ST burden: Bangladesh, India and Pakistan to explore ST and smoking uptake, use and health promoting strategies. Before running that longitudinal study, we assessed the feasibility of conducting such a multi country survey using a mixed-methods design. The survey (and feasibility study) was conducted in 24 secondary schools (eight per country, three classes per school). Three data sources, researcher records/fieldnotes, survey data of 1179 students, and interview/focus group discussion data from 24 headteachers, 64 teachers and 76 students, were used to understand the feasibility of three study tasks: 1) selecting, recruiting, and retaining schools and student participants; 2) survey administration; and 3) robustness of the data collection instruments. The datasets were analysed separately and triangulated. Overall, we could select and recruit schools and students using consistent methods across countries although recruitment was challenged by securing higher authority permissions and parental consent. Recommended improvements were for permission/consent processes. Survey administration was generally feasible and acceptable with recommendations for scheduling and researcher-student ratios. Questionnaire completion was 83%-100% across countries, with suggestions to improve readability and understanding, addressing students' queries and questionnaire simplification. Due to COVID-19, we could not conduct follow-up surveys, so were unable to assess school or student retention. In conclusion, incorporating the lessons learnt from this study would improve the feasibility of conducting such a multi-country survey in the future. Reported benefits included increasing tobacco health risks' knowledge with potential for increased tobacco control support.

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/.

Artificial selection reveals complex genetic architecture of shoot branching and its response to nitrate supply in Arabidopsis.

Quantitative traits may be controlled by many loci, many alleles at each locus, and subject to genotype-by-environment interactions, making them difficult to map. One example of such a complex trait is shoot branching in the model plant Arabidopsis, and its plasticity in response to nitrate. Here, we use artificial selection under contrasting nitrate supplies to dissect the genetic architecture of this complex trait, where loci identified by association mapping failed to explain heritability estimates. We found a consistent response to selection for high branching, with correlated responses in other traits such as plasticity and flowering time. Genome-wide scans for selection and simulations suggest that at least tens of loci control this trait, with a distinct genetic architecture between low and high nitrate treatments. While signals of selection could be detected in the populations selected for high branching on low nitrate, there was very little overlap in the regions selected in three independent populations. Thus the regulatory network controlling shoot branching can be tuned in different ways to give similar phenotypes.

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.

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.

Smokeless tobacco products, supply chain and retailers' practices in England: a multimethods study to inform policy.

BACKGROUND: In England, many people of South Asian origin consume smokeless tobacco (ST). ST use can lead to oral cancer, which is disproportionately high in South Asians. Our aims were to assess the compliance of ST product retailers with statutory regulations and to explore the supply chain of ST. METHODS: We undertook a multimethods study between August 2017 and July 2019 in five English boroughs with a high proportion of ethnic South Asians. We purchased ST products and conducted field surveys with ST retailers at point of sale. Qualitative interviews were conducted with ST retailers and suppliers. ST packs were assessed for regulatory compliance, while quantitative and qualitative data triangulated information on retailers' practices and the ST supply chain. RESULTS: We collected 41 unique ST products, which included dry snuff, naswar, gutka, chewing tobacco and zarda. ST products were not registered, and demonstrated low compliance with health warning (14.6%) and packaging (56.1%) requirements. ST availability in surveyed boroughs was high (38.2%-69.7%); dry snuff, naswar and zarda were most commonly available. ST retailers demonstrated limited knowledge of regulations, and one-third were found to advertise ST at point of sale. Qualitative insights revealed illicit supply and distribution networks, as well as ST production in discreet locations. CONCLUSION: ST products are widely available in England, yet non-compliant with statutory regulations. In order to safeguard consumers, in particular ethnic South Asians, stronger efforts are needed to regulate the supply chain of ST at both national and international levels.

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.

Global burden of disease due to smokeless tobacco consumption in adults: an updated analysis of data from 127 countries.

BACKGROUND: Smokeless tobacco (ST) is consumed by more than 300 million people worldwide. The distribution, determinants and health risks of ST differ from that of smoking; hence, there is a need to highlight its distinct health impact. We present the latest estimates of the global burden of disease due to ST use. METHODS: The ST-related disease burden was estimated for all countries reporting its use among adults. Using systematic searches, we first identified country-specific prevalence of ST use in men and women. We then revised our previously published disease risk estimates for oral, pharyngeal and oesophageal cancers and cardiovascular diseases by updating our systematic reviews and meta-analyses of observational studies. The updated country-specific prevalence of ST and disease risk estimates, including data up to 2019, allowed us to revise the population attributable fraction (PAF) for ST for each country. Finally, we estimated the disease burden attributable to ST for each country as a proportion of the DALYs lost and deaths reported in the 2017 Global Burden of Disease study. RESULTS: ST use in adults was reported in 127 countries; the highest rates of consumption were in South and Southeast Asia. The risk estimates for cancers were also highest in this region. In 2017, at least 2.5 million DALYs and 90,791 lives were lost across the globe due to oral, pharyngeal and oesophageal cancers that can be attributed to ST. Based on risk estimates obtained from the INTERHEART study, over 6 million DALYs and 258,006 lives were lost from ischaemic heart disease that can be attributed to ST. Three-quarters of the ST-related disease burden was among men. Geographically, > 85% of the ST-related burden was in South and Southeast Asia, India accounting for 70%, Pakistan for 7% and Bangladesh for 5% DALYs lost. CONCLUSIONS: ST is used across the globe and poses a major public health threat predominantly in South and Southeast Asia. While our disease risk estimates are based on a limited evidence of modest quality, the likely ST-related disease burden is substantial. In high-burden countries, ST use needs to be regulated through comprehensive implementation of the World Health Organization Framework Convention for Tobacco Control.

Compliance of smokeless tobacco supply chain actors and products with tobacco control laws in Bangladesh, India and Pakistan: protocol for a multicentre sequential mixed-methods study.

INTRODUCTION: South Asia is home to more than 300 million smokeless tobacco (ST) users. Bangladesh, India and Pakistan as signatories to the Framework Convention for Tobacco Control (FCTC) have developed policies aimed at curbing the use of tobacco. The objective of this study is to assess the compliance of ST point-of-sale (POS) vendors and the supply chain with the articles of the FCTC and specifically with national tobacco control laws. We also aim to assess disparities in compliance with tobacco control laws between ST and smoked tobacco products. METHODS AND ANALYSIS: The study will be carried out at two sites each in Bangladesh, India and Pakistan. We will conduct a sequential mixed-methods study with five components: (1) mapping of ST POS, (2) analyses of ST samples packaging, (3) observation, (4) survey interviews of POS and (5) in-depth interviews with wholesale dealers/suppliers/manufacturers of ST. We aim to conduct at least 300 POS survey interviews and observations, and 6-10 in-depth interviews in each of the three countries. Data collection will be done by trained data collectors. The main statistical analysis will report the frequencies and proportions of shops that comply with the FCTC and local tobacco control policies, and provide a 95% CI of these estimates. The qualitative in-depth interview data will be analysed using the framework approach. The findings will be connected, each component informing the focus and/or design of the next component. ETHICS AND DISSEMINATION: Ethical approvals for the study have been received from the Health Sciences Research Governance Committee at the University of York, UK. In-country approvals were taken from the National Bioethics Committee in Pakistan, the Bangladesh Medical Research Council and the Indian Medical Research Council. Our results will be disseminated via scientific conferences, peer-reviewed research publications and press releases.

Protocol for a feasibility study of longitudinal surveys to assess the impact of policies on tobacco use among school-going adolescents in South Asia.

Background: Smokeless tobacco (ST) use is common among youth in South Asia where 85% of the world's 300 million ST users live and use the most lethal ST forms. Little is known about the impact of tobacco control policies on the youth ST uptake in those countries. We planned to conduct longitudinal surveys among secondary school students to evaluate existing tobacco control policies on ST uptake and use, and a feasibility study for that prospective, observational cohort study. Study objectives: (1) To demonstrate the feasibility of selection, recruitment and retention of schools and of study participants; (2) To assess the feasibility and acceptability of the study procedure and study tool (questionnaire); (3) To assess if the questionnaire can assess tobacco uptake and use, and the potential predictors of tobacco uptake and use of the envisaged main study. Methods and analysis: The feasibility study will be conducted in two administrative areas within each of three South Asian countries: Bangladesh, India and Pakistan. We will use both quantitative and qualitative data collection methods. Eight eligible secondary schools will be randomly selected within purposively selected sub-districts from each country. We plan to conduct one baseline and one follow up survey among secondary school students, one year apart. At each time point, data on tobacco uptake and the potential predictors will be collected from students via self-administered questionnaires. The qualitative component will be embedded into the study with each round of data collection to assess the acceptability of the study instrument (questionnaire) and data collection methods, via focus group discussions with students and semi-structured interviews with schoolteachers. Recruitment and retention rates, completeness of the questionnaires, frequencies and associations of tobacco use and explanatory variables will be reported. Data gathered from the focus group and interviews will be analysed using the framework approach.

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.

The safety, effectiveness and cost-effectiveness of cytisine in achieving six-month continuous smoking abstinence in tuberculosis patients-protocol for a double-blind, placebo-controlled randomized trial.

BACKGROUND AND AIMS: Tuberculosis (TB) patients who quit smoking have much better disease outcomes than those who continue to smoke. In general populations, behavioural support combined with pharmacotherapy is the most effective strategy in helping people to quit. However, there is no evidence for the effectiveness of this strategy in TB patients who smoke. We will assess the safety, effectiveness and cost-effectiveness of cytisine-a low-cost plant-derived nicotine substitute-for smoking cessation in TB patients compared with placebo, over and above brief behavioural support. DESIGN: Two-arm, parallel, double-blind, placebo-controlled, multi-centre (30 sites in Bangladesh and Pakistan), individually randomized trial. SETTING: TB treatment centres integrated into public health care systems in Bangladesh and Pakistan. PARTICIPANTS: Newly diagnosed (in the last 4 weeks) adult pulmonary TB patients who are daily smokers (with or without dual smokeless tobacco use) and are interested in quitting (n = 2388). MEASUREMENTS: The primary outcome measure is biochemically verified continuous abstinence from smoking at 6 months post-randomization, assessed using Russell Standard criteria. The secondary outcome measures include continuous abstinence at 12 months, lapses and relapses; clinical TB outcomes; nicotine dependency and withdrawal; and adverse events. COMMENTS: This is the first smoking cessation trial of cytisine in low- and middle-income countries evaluating both cessation and TB outcomes. If found effective, cytisine could become the most affordable cessation intervention to help TB patients who smoke.

A Policy Perspective on the Global Use of Smokeless Tobacco.

BACKGROUND: Globally, over 300 million people consume diverse smokeless tobacco (ST) products. They are addictive, cause cancer, increased cardiovascular mortality risks and poor pregnancy outcomes. PURPOSE OF REVIEW: To identify gaps in implementing key ST demand-reduction measures, focused literature reviews were conducted and findings synthesized according to relevant WHO Framework Convention on Tobacco Control (FCTC) Articles. RECENT FINDINGS: The literature supports implementation of ST demand-reduction measures. For taxation, labelling and packaging, most administrations have weaker policies for ST than cigarettes. Capacity to regulate ST contents and offer cessation support is lacking. There is poor compliance with bans on ST advertising, promotion and sponsorship. SUMMARY: The literature on implementation of WHO FCTC for ST is limited. Although strengths of ST demand-control activities are currently identifiable from available literature, full implementation of FCTC is lacking. A wider evidence-based response to WHO FCTC is proposed, particularly for countries facing the greatest disease burdens.

Zygotic resetting of the HISTONE 3 variant repertoire participates in epigenetic reprogramming in Arabidopsis.

In most eukaryotes, the HISTONE 3 family comprises several variants distinguished by their amino acid sequence, localization, and correlation with transcriptional activity. Transgenerational inheritance of epigenetic information carried by histones is still unclear. In addition to covalent histone modifications, the mosaic distribution of H3 variants onto chromatin has been proposed to provide a new level of epigenetic information. To study the transmission of patterns of H3 variants through generations, we combined transcriptional profiling and live imaging of the 13 H3 variants encoded by the Arabidopsis plant genome. In comparison with somatic cells, only a restricted number of H3 variants are present in male and female gametes. Upon fertilization, H3 variants contributed by both gametes are actively removed from the zygote chromatin. The somatic H3 composition is restored in the embryo by de novo synthesis of H3 variants. A survey of Arabidopsis homologs of animal H3 chaperones suggests that removal of parental H3 from the zygote nucleus relies on a new mechanism. Our results suggest that reprogramming of parental genomes in the zygote limits the inheritance of epigenetic information carried by H3 variants across generations.