Undernutrition as a risk factor for tuberculosis disease.

BACKGROUND: Tuberculosis (TB) is a leading cause of mortality due to an infectious disease, with an estimated 1.6 million deaths due to TB in 2022. Approximately 25% of the global population has TB infection, giving rise to 10.6 million episodes of TB disease in 2022. Undernutrition is a key risk factor for TB and was linked to an estimated 2.2 million TB episodes in 2022, as outlined in the World Health Organization (WHO) Global Tuberculosis Report. OBJECTIVES: To determine the prognostic value of undernutrition in the general population of adults, adolescents, and children for predicting tuberculosis disease over any time period. SEARCH METHODS: We searched the literature databases MEDLINE (via PubMed) and WHO Global Index Medicus, as well as the WHO International Clinical Trials Registry Platform (ICTRP) on 3 May 2023 (date of last search for all databases). We placed no restrictions on the language of publication. SELECTION CRITERIA: We included retrospective and prospective cohort studies, irrespective of publication status or language. The target population comprised adults, adolescents, and children from diverse settings, encompassing outpatient and inpatient cohorts, with varying comorbidities and risk of exposure to tuberculosis. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology and the Quality In Prognosis Studies (QUIPS) tool to assess the risk of bias of the studies. Prognostic factors included undernutrition, defined as wasting, stunting, and underweight, with specific measures such as body mass index (BMI) less than two standard deviations below the median for children and adolescents and low BMI scores (< 18.5) for adults and adolescents. Prognostication occurred at enrolment/baseline. The primary outcome was the incidence of TB disease. The secondary outcome was recurrent TB disease. We performed a random-effects meta-analysis for the adjusted hazard ratios (HR), risk ratios (RR), or odds ratios (OR), employing the restricted maximum likelihood estimation. We rated the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 51 cohort studies with over 27 million participants from the six WHO regions. Sixteen large population-based studies were conducted in China, Singapore, South Korea, and the USA, and 25 studies focused on people living with HIV, which were mainly conducted in the African region. Most studies were in adults, four in children, and three in children and adults. Undernutrition as an exposure was usually defined according to standard criteria; however, the diagnosis of TB did not include a confirmatory culture or molecular diagnosis using a WHO-approved rapid diagnostic test in eight studies. The median follow-up time was 3.5 years, and the studies primarily reported an adjusted hazard ratio from a multivariable Cox-proportional hazard model. Hazard ratios (HR) The HR estimates represent the highest certainty of the evidence, explored through sensitivity analyses and excluding studies at high risk of bias. We present 95% confidence intervals (CI) and prediction intervals, which present between-study heterogeneity represented in a measurement of the variability of effect sizes (i.e. the interval within which the effect size of a new study would fall considering the same population of studies included in the meta-analysis). Undernutrition may increase the risk of TB disease (HR 2.23, 95% CI 1.83 to 2.72; prediction interval 0.98 to 5.05; 23 studies; 2,883,266 participants). The certainty of the evidence is low due to a moderate risk of bias across studies and inconsistency. When stratified by follow-up time, the results are more consistent across < 10 years follow-up (HR 2.02, 95% CI 1.74 to 2.34; prediction interval 1.20 to 3.39; 22 studies; 2,869,077 participants). This results in a moderate certainty of evidence due to a moderate risk of bias across studies. However, at 10 or more years of follow-up, we found only one study with a wider CI and higher HR (HR 12.43, 95% CI 5.74 to 26.91; 14,189 participants). The certainty of the evidence is low due to the moderate risk of bias and indirectness. Odds ratio (OR) Undernutrition may increase the odds of TB disease, but the results are uncertain (OR 1.56, 95% CI 1.13 to 2.17; prediction interval 0.61 to 3.99; 8 studies; 173,497 participants). Stratification by follow-up was not possible as all studies had a follow-up of < 10 years. The certainty of the evidence is very low due to the high risk of bias and inconsistency. Contour-enhanced funnel plots were not reported due to the few studies included. Risk ratio (RR) Undernutrition may increase the risk of TB disease (RR 1.95, 95% CI 1.72 to 2.20; prediction interval 1.49 to 2.55; 4 studies; 1,475,867 participants). Stratification by follow-up was not possible as all studies had a follow-up of < 10 years. The certainty of the evidence is low due to the high risk of bias. Contour-enhanced funnel plots were not reported due to the few studies included. AUTHORS' CONCLUSIONS: Undernutrition probably increases the risk of TB two-fold in the short term (< 10 years) and may also increase the risk in the long term (> 10 years). Policies targeted towards the reduction of the burden of undernutrition are not only needed to alleviate human suffering due to undernutrition and its many adverse consequences, but are also an important part of the critical measures for ending the TB epidemic by 2030. Large population-based cohorts, including those derived from high-quality national registries of exposures (undernutrition) and outcomes (TB disease), are needed to provide high-certainty estimates of this risk across different settings and populations, including low and middle-income countries from different WHO regions. Moreover, studies including children and adolescents and state-of-the-art methods for diagnosing TB would provide more up-to-date information relevant to practice and policy. FUNDING: World Health Organization (203256442). REGISTRATION: PROSPERO registration: CRD42023408807 Protocol: https://doi.org/10.1002/14651858.CD015890.

Self-management of chronic, non-communicable diseases in South Asian settings: A systematic mixed-studies review.

Self-management is crucial in mitigating the impacts of a growing non-communicable disease (NCD) burden, particularly in Low and Middle-Income countries. What influences self-management in these settings, however, is poorly understood. We aimed to identify the determinants of self-management in the high NCD region of South Asia and explore how they influence self-management. A systematic mixed-studies review was conducted. Key electronic databases [MEDLINE (1946+), Embase (1974+), PsycInfo (1967+) and CINAHL (EBSCOhost)] in March 2022 (and updated in April 2023) were searched for studies on the self-management of four high-burden NCD groups: cardiovascular diseases, type 2 diabetes, chronic respiratory diseases and depression. Study characteristics and quantitative data were extracted using a structured template, and qualitative information was extracted using NVivo. Quality appraisal was done using the Mixed Methods Assessment Tool (MMAT). Quantitative findings were organised using the Commission on Social Determinants of Health (CSDH) framework and synthesised narratively, supported by effect direction plots. Qualitative findings were thematically synthesised. Both were integrated in a mixed synthesis. Forty-four studies (26 quantitative, 16 qualitative and 2 mixed-methods studies) were included, the majority of which were conducted in urban settings and among individuals with diabetes and cardiovascular diseases. Higher age, education, and income (structural determinants), health-related knowledge, social support and self-efficacy (psychosocial determinants), longer illness duration and physical comorbidity (biologic determinants), and the affordability of medicine (health-system determinants) were key determinants of self-management. Qualitative themes highlighted the role of financial adversity and the social and physical environment in shaping self-management.A complex interplay of structural and intermediary social determinants shapes self-management in South Asian settings. Multi-component, whole-systems approaches could boost self-management in these settings. Key areas include empowerment and education of patients and wider community, design and delivery of bespoke behavioural interventions and a stronger emphasis on supporting self-management in healthcare settings.

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/.

Effectiveness of behavior change interventions for smoking cessation among expectant and new fathers: findings from a systematic review.

BACKGROUND: Smoking cessation during pregnancy and the postpartum period by both women and their partners offers multiple health benefits. However, compared to pregnant/postpartum women, their partners are less likely to actively seek smoking cessation services. There is an increased recognition about the importance of tailored approaches to smoking cessation for expectant and new fathers. While Behavior Change Interventions (BCIs) are a promising approach for smoking cessation interventions, evidence on effectiveness exclusively among expectant and new fathers are fragmented and does not allow for many firm conclusions to be drawn. METHODS: We conducted a systematic review on effectiveness of BCIs on smoking cessation outcomes of expectant and new fathers both through individual and/or couple-based interventions. Peer reviewed articles were identified from eight databases without any date or language restriction.Two independent reviewers screened studies for relevance, assessed methodological quality of relevant studies, and extracted data from studies using a predeveloped data extraction sheet. RESULTS: We retrieved 1222 studies, of which 39 were considered for full text screening after reviewing the titles and abstracts. An additional eight studies were identified from reviewing the reference list of review articles picked up by the databases search. A total of nine Randomised Control Trials were included in the study. Six studies targeted expectant/new fathers, two targeted couples and one primarily targeted women with an intervention component to men. While the follow-up measurements for men varied across studies, the majority reported biochemically verified quit rates at 6 months. Most of the interventions showed positive effects on cessation outcomes. BCI were heterogenous across studies. Findings are suggestive of gender targeted interventions being more likely to have positive cessation outcomes. CONCLUSIONS: This systematic review found limited evidence supporting the effectiveness of BCI among expectant and new fathers, although the majority of studies show positive effects of these interventions on smoking cessation outcomes. There remains a need for more research targeted at expectant and new fathers. Further, there is a need to identify how smoking cessation service delivery can better address the needs of (all) gender(s) during pregnancy.

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.

Climate change and health in school-based education: A scoping review protocol.

Taking into account the adverse impacts of climate change on human health, the importance of increasing knowledge and gaining essential skills is necessary to mitigate and adapt to its impacts and protect human health. Researchers and experts are urging for more research in the climate-health nexus, as well as calling for efforts that establish climate and health educational goals. They encourage the development of agreed upon, articulated science-based curricula and resources addressing climate-health issues. This review aims to map out the current state of integration of climate change education in school-based education across the world and identify the human health topics included. Furthermore, it aims to explore the extents to which levels of prevention and health co-benefits of climate mitigation and adaptation are covered within the framework of school-based climate change education. Five electronic databases will be searched for peer reviewed articles in English, from year 2000-to May 2022. The findings from the study will be useful to school curricula developers looking to expand climate change education. This review will also highlight potential research gaps in education on climate change-related health in schools. The scoping review was preregistered with the Open Science Framework [registration DOI: https://doi.org/10.17605/OSF.IO/8U5GK].

Policies regulating retail environment to reduce tobacco availability: A scoping review.

Background: In 2005, the World Health Organization Framework Convention on Tobacco Control (WHO FCTC) entered into force. This treaty was developed in response to the global tobacco epidemic, and it includes measures to reduce both demand for and supply of tobacco. The measures related to demand reduction include raising tax, providing cessation services, promoting smoke free public places, banning advertising, and raising awareness. However, there are a limited number of measures for supply reduction, and these mainly include fighting illicit trade, banning sales to minors and providing alternatives to tobacco workers and growers. Unlike regulation of many other goods and services that have been subjected to retail restrictions, there is a lack of resources about restricting tobacco availability through regulation of tobacco retail environment. Considering the potential of retail environment regulations in reducing tobacco supply and consequently reducing tobacco use, this scoping review aims to identify relevant measures. Methods: This review examines interventions, policies, and legislations to regulate tobacco retail environment to reduce tobacco availability. This was done by searching the WHO FCTC and its Conference of Parties decisions, a gray literature search including tobacco control databases, a scoping communication with the Focal Points of the 182 WHO FCTC Parties, and a databases search in PubMed, EMBASE, Cochrane Library, Global Health, and Web of Science. Results: Themes of policies were identified to reduce tobacco availability by regulating retail environment: four WHO FCTC and twelve non-WHO FCTC policies. The WHO FCTC policies included requiring a license to sell tobacco, banning tobacco sale via vending machines, promoting economically alternative activities to individual sellers, and banning ways of sale that constitute a way of advertising, promotion, and sponsorships. The Non-WHO FCTC policies included banning tobacco home delivery, tray sale, tobacco retail outlets in or within a minimum distance from specific facilities, sale in specific retail outlets, and sale of tobacco or one or more of its products, in addition to restricting tobacco retail outlets per density of population and per geographic area, capping the tobacco amount allowed per purchase, limiting the number of hours or days in which tobacco can be sold, requiring a minimum distance between tobacco retailers, reducing tobacco products availability and proximity within a retail outlet, and restricting sale to government controlled outlets. Discussion and conclusion: Studies show the effects of regulation of the retail environment in influencing overall tobacco purchases, and there is evidence that having fewer retails reduces the level of impulse purchasing of cigarettes and tobacco goods. The measures covered by WHO FCTC are much more implemented than ones not covered by it. Although not all widely implemented, many themes of limiting tobacco availability by regulating tobacco retail environment are available. Further studies to explore such measures and the adoption of the effective ones under the WHO FCTC decisions, could possibly increase their implementation globally to reduce tobacco availability.

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.

Health Equity in Climate Change Policies and Public Health Policies Related to Climate Change: Protocol for a Systematic Review.

The relationship between risks to health equity and climate change is well established, and various international organizations and literature has called for intersectoral action for tackling these issues. While there is a growing recognition of the importance of equity-focused responses to climate change, if and how health equity measures are incorporated into climate-change-related policy decisions has not yet been adequately explored. There are numerous approaches and frameworks for conducting policy analysis, and for understanding equity in the context of climate change and public health separately; however, a comprehensive framework for exploring the complexity of these interacting factors is hard to find. This review aims to systematically identify policy analysis frameworks and studies focusing on health equity in climate change related policies. Five electronic databases will be searched for peer-reviewed articles in English and from 2000. Articles will be subjected to systematic retrieval and quality assessment, and thematic analysis will be used for data analysis. The study findings will provide insight into different existing policy-analysis frameworks and policy-analysis approaches to understand health equity considerations in climate change policies and in health policies related to climate change.

Heat-health action planning in the WHO European Region: Status and policy implications.

Adverse health effects from extreme heat remain a major risk, especially in a changing climate. Several European countries have implemented heat health action plans (HHAPs) to prevent ill health and excess mortality from heat. This paper assesses the state of implementation of HHAPs in the WHO European Region and discusses barriers and successes since the early 2000s. The results are based on a web-based survey among 53 member states on the current national and federal HHAPs in place. Guided by the eight core elements of HHAPs as outlined by the WHO Regional Office for Europe guidance from 2008, we analyzed which elements were fully or partially implemented and which areas of improvement countries identified. HHAP adaptations to account for COVID-19 were sought via literature search and expert consultations. 27 member states provided information, of which 17 countries reported having a HHAP. Five out of eight core elements, namely agreement on a lead body, accurate and timely alert systems, heat-related health information plans, strategies to reduce health exposure, and care for vulnerable groups, were at least partially implemented in all 17 plans. Alert systems were implemented most often at 94%. The least often implemented items were real-time surveillance, long-term urban planning, and preparedness of health and social systems. Five countries had published COVID-19 guidance online. Our findings suggest a progressive improvement in the development and rollout of HHAPs overall and awareness of vulnerable population groups in WHO/Europe, while integration of HHAPs into long-term climate change and health planning remains a challenge.

Attitudes of smokers towards tobacco control policies: findings from the Studying Tobacco users of Pakistan (STOP) survey.

BACKGROUND: Public attitude is a political driver in successful implementation of tobacco control policies. We assessed support for a range of tobacco control policies among smokers in Pakistan. METHODS: We conducted a household survey among adult smokers in 10 cities of Pakistan, using a two-stage random sampling strategy to select households and Kish grid method to select one smoker per household. Attitudes were measured using a five-point ordinal scale on four policy statements: a complete ban on tobacco sale within 10 years; raising the legal age to buy tobacco from 18 to 21; increasing tobacco taxes to fund healthcare and a ban on smoking in cars with minors. RESULTS: 6014 participants were interviewed between September 2019 and March 2020. Most participants demonstrated strong support for all policy statements: a ban on smoking in cars with minors (86.5%); a complete ban on tobacco sale within 10 years (82.1%); raising the legal age to buy tobacco (77.9%) and increasing tobacco taxes (68.1%). Smokers' support for tobacco control policies increased with age but decreased with higher educational attainment and heaviness of smoking. CONCLUSIONS: There is strong support among smokers in Pakistan to strengthen tobacco control. Given this, policy-makers should strongly consider strengthening existing national policies on tobacco control.

Illicit cigarette trade in the cities of Pakistan: comparing findings between the consumer and waste recycle store surveys.

BACKGROUND: Concerns about the magnitude of illicit cigarette trade have prevented the Government of Pakistan from increasing tobacco taxes. We estimated the proportion of illicit cigarettes sold in Pakistani cities. Moreover, we compared two methods for collecting cigarette packs and investigated if the illicit cigarette trade equates to tax evasion. METHOD: We analysed cigarette packs collected from 10 cities of Pakistan using two methods: consumer survey based on a two-stage random sampling strategy to recruit adult smokers and photograph their cigarette packs and waste recycle store survey to purchase used cigarette packs. Cigarettes were considered illicit if any one of the following was absent from their packs: text and pictorial health warning, underage sale prohibition warning, retail price and manufacturer's name. From the consumer survey, we also estimated the proportion of smokers who purchased loose cigarettes (illegal) and packs below the minimum retail price. Taxation officers (n=4) were consulted to assess their level of confidence in judging tax evasion using the above criteria. RESULTS: Out of 2416 cigarette packs in the consumer survey, 454 (17.8%; 95% CI 15.4% to 20.2%) were illicit. Similarly, out of 6213 packs from waste recycle shops, 1046 (16.8%; 95% CI 15.9% to 17.7%) were illicit; the difference was not statistically significant (p=0.473). Among consumers, 29.5% bought loose cigarettes and 13.8% paid less than the minimum retail price. The taxation officers considered the manufacturer's name and retail price on cigarette packs as the most relevant criteria to detect tax evasion. CONCLUSIONS: One in six cigarette packs consumed in Pakistan could be illicit. These figures are far less than those propagated by the tobacco industry. Collecting packs from waste recycle stores is an efficient and valid method to estimate illicit cigarette trade.

Impacts of High Environmental Temperatures on Congenital Anomalies: A Systematic Review.

Links between heat exposure and congenital anomalies have not been explored in detail despite animal data and other strands of evidence that indicate such links are likely. We reviewed articles on heat and congenital anomalies from PubMed and Web of Science, screening 14,880 titles and abstracts in duplicate for articles on environmental heat exposure during pregnancy and congenital anomalies. Thirteen studies were included. Most studies were in North America (8) or the Middle East (3). Methodological diversity was considerable, including in temperature measurement, gestational windows of exposure, and range of defects studied. Associations were detected between heat exposure and congenital cardiac anomalies in three of six studies, with point estimates highest for atrial septal defects. Two studies with null findings used self-reported temperature exposures. Hypospadias, congenital cataracts, renal agenesis/hypoplasia, spina bifida, and craniofacial defects were also linked with heat exposure. Effects generally increased with duration and intensity of heat exposure. However, some neural tube defects, gastroschisis, anopthalmia/microphthalmia and congenital hypothyroidism were less frequent at higher temperatures. While findings are heterogenous, the evidence raises important concerns about heat exposure and birth defects. Some heterogeneity may be explained by biases in reproductive epidemiology. Pooled analyses of heat impacts using registers of congenital anomalies are a high priority.

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.

Supply Chain Actors' Willingness to Switch the Business of Smokeless Tobacco: A Mixed-Methods Study on Naswar Business in Pakistan.

INTRODUCTION: Provision of alternate livelihoods to smokeless tobacco (SLT) supply chain (SC) actors can help in curtailing SLT business and its consumption. We explored the reasons for SC actors' engagement in Naswar (SLT used in South Asia) business and their willingness to switch to other alternatives. AIMS AND METHODS: We conducted an equal-status concurrent mixed-methods study in four districts of Khyber Pakhtunkhwa province of Pakistan. We surveyed 286 general points of sale (GPOS) and exclusive Naswar (EN) vendors through multistage cluster sampling. Additionally, we interviewed 15 tobacco farmers interpretively, being distinct from other SC actors. We assessed the association between vendors' willingness to switch and their awareness about tobacco-harms, profit margin, Naswar as a family business, length of business, education level, and shop type using logistic regression. Qualitative data assessed the farmer's viable alternatives to switch and were analyzed using deductive-inductive thematic analysis. RESULTS: Product demand-77% and profit margins-75% were the main drivers for selling SLT by EN vendors. Half of the GPOS and 25% EN vendors expressed willingness to stop Naswar's sale. Vendors aware of tobacco-harms were more willing to switch, but less likely to switch if Naswar was perceived to bring "good profit." Farmers were mainly cultivating tobacco because of profitability, family-run farm, and perceived land-suitability for tobacco. Lack of government support was main constraint for farmers looking to switch. CONCLUSIONS: A considerable portion of Naswar SC actors in Pakistan are willing to switch to viable alternatives, with profitability of alternatives, support from authorities, and social obligations as key considerations in doing so. IMPLICATIONS: This study highlights that good profit margins in the Naswar business, lack of awareness of tobacco-related health harms, and absence of the government's support are key detriments to switching to alternative businesses among Naswar SC actors in Pakistan. These findings are the first to come out in the context of both Pakistan and Naswar product, making a case for policy interventions focusing on tax increases, awareness campaigns about tobacco-harms, and a proactive role by the government to provide support for the security of livelihoods to those tobacco SC actors who want to switch to other alternatives.

Implementing smokeless tobacco control policy in Pakistan: a qualitative study among Naswar supply chain actors.

OBJECTIVE: To obtain insights into the perceptions of barriers and facilitators to implementation of the WHO Framework Convention on Tobacco Control (FCTC) among smokeless tobacco (SLT) supply chain actors in the Khyber Pakhtunkhwa province of Pakistan. METHODS: We conducted a qualitative study to investigate the perceptions about SLT control policy formulation and implementation among exclusive Naswar sellers and point of sale vendors. We conducted five focus group discussions in three districts of Khyber Pakhtunkhwa using combined deductive-inductive thematic analyses. RESULTS: We identified three central themes that potentially impact policy formulation, its implementation and application. The first theme examines the role of children in the Naswar business: as potential customers, and as potential heirs to a Naswar-selling business. A second theme targets the 'business of Naswar', which includes a specific identity of Naswar sellers, its potential to generate profits and the special case of Naswar regulation as a socially accepted and culturally rooted product. The third theme addresses the unusual ingredients of Naswar and its production process, making Naswar a health risk for consumers and producers. We also report conflicting views regarding SLT control among the supply chain actors. CONCLUSIONS: This study provides insights into the perceptions of important SLT supply-side stakeholders regarding various SLT control policy options based on the FCTC. While there is some opposition to policy approaches like taxation and switching of business, implementing a ban on selling SLT to minors may be a viable option for policymakers in the short term.

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.

Transdisciplinary Research Priorities for Human and Planetary Health in the Context of the 2030 Agenda for Sustainable Development.

Human health and wellbeing and the health of the biosphere are inextricably linked. The state of Earth's life-support systems, including freshwater, oceans, land, biodiversity, atmosphere, and climate, affect human health. At the same time, human activities are adversely affecting natural systems. This review paper is the outcome of an interdisciplinary workshop under the auspices of the Future Earth Health Knowledge Action Network (Health KAN). It outlines a research agenda to address cross-cutting knowledge gaps to further understanding and management of the health risks of these global environmental changes through an expert consultation and review process. The research agenda has four main themes: (1) risk identification and management (including related to water, hygiene, sanitation, and waste management); food production and consumption; oceans; and extreme weather events and climate change. (2) Strengthening climate-resilient health systems; (3) Monitoring, surveillance, and evaluation; and (4) risk communication. Research approaches need to be transdisciplinary, multi-scalar, inclusive, equitable, and broadly communicated. Promoting resilient and sustainable development are critical for achieving human and planetary health.

Associations between high temperatures in pregnancy and risk of preterm birth, low birth weight, and stillbirths: systematic review and meta-analysis.

OBJECTIVE: To assess whether exposure to high temperatures in pregnancy is associated with increased risk for preterm birth, low birth weight, and stillbirth. DESIGN: Systematic review and random effects meta-analysis. DATA SOURCES: Medline and Web of Science searched up to September 2018, updated in August 2019. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Clinical studies on associations between high environmental temperatures, and preterm birth, birth weight, and stillbirths. RESULTS: 14 880 records and 175 full text articles were screened. 70 studies were included, set in 27 countries, seven of which were countries with low or middle income. In 40 of 47 studies, preterm births were more common at higher than lower temperatures. Exposures were classified as heatwaves, 1°C increments, and temperature threshold cutoff points. In random effects meta-analysis, odds of a preterm birth rose 1.05-fold (95% confidence interval 1.03 to 1.07) per 1°C increase in temperature and 1.16-fold (1.10 to 1.23) during heatwaves. Higher temperature was associated with reduced birth weight in 18 of 28 studies, with considerable statistical heterogeneity. Eight studies on stillbirths all showed associations between temperature and stillbirth, with stillbirths increasing 1.05-fold (1.01 to 1.08) per 1°C rise in temperature. Associations between temperature and outcomes were largest among women in lower socioeconomic groups and at age extremes. The multiple temperature metrics and lag analyses limited comparison between studies and settings. CONCLUSIONS: Although summary effect sizes are relatively small, heat exposures are common and the outcomes are important determinants of population health. Linkages between socioeconomic status and study outcomes suggest that risks might be largest in low and middle income countries. Temperature rises with global warming could have major implications for child health. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD 42019140136 and CRD 42018118113.

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.