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 Role of the Private Sector in the COVID-19 Pandemic: Experiences From Four Health Systems.

As societies urbanize, their populations have become increasingly dependent on the private sector for essential services. The way the private sector responds to health emergencies such as the COVID-19 pandemic can determine the health and economic wellbeing of urban populations, an effect amplified for poorer communities. Here we present a qualitative document analysis of media reports and policy documents in four low resource settings-Bangladesh, Ghana, Nepal, Nigeria-between January and September 2020. The review focuses on two questions: (i) Who are the private sector actors who have engaged in the COVID-19 first wave response and what was their role?; and (ii) How have national and sub-national governments engaged in, and with, the private sector response and what have been the effects of these engagements? Three main roles of the private sector were identified in the review. (1) Providing resources to support the public health response. (2) Mitigating the financial impact of the pandemic on individuals and businesses. (3) Adjustment of services delivered by the private sector, within and beyond the health sector, to respond to pandemic-related business challenges and opportunities. The findings suggest that a combination of public-private partnerships, contracting, and regulation have been used by governments to influence private sector involvement. Government strategies to engage the private sector developed quickly, reflecting the importance of private services to populations. However, implementation of regulatory responses, especially in the health sector, has often been weak reflecting the difficulty governments have in ensuring affordable, quality private services. Lessons for future pandemics and other health emergencies include the need to ensure that essential non-pandemic health services in the government and non-government sector can continue despite elevated risks, surge capacity to minimize shortages of vital public health supplies is available, and plans are in place to ensure private workplaces remain safe and livelihoods protected.

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.

Prevalence of physical health conditions and health risk behaviours in people with severe mental illness in South Asia: protocol for a cross-sectional study (IMPACT SMI survey).

INTRODUCTION: People with severe mental illness (SMI) die on average 10-20 years earlier than the general population. Most of these deaths are due to physical health conditions. The aim of this cross-sectional study is to determine the prevalence of physical health conditions and their associations with health-risk behaviours, health-related quality of life and various demographic, behavioural, cognitive, psychological and social variables in people with SMI attending specialist mental health facilities in South Asia. METHODS AND ANALYSIS: We will conduct a survey of patients with SMI attending specialist mental health facilities in Bangladesh, India and Pakistan (n=4500). Diagnosis of SMI will be confirmed using the Mini-international neuropsychiatric interview V.6.0. We will collect information about physical health and related health-risk behaviours (WHO STEPwise approach to Surveillance (STEPS)); severity of common mental disorders (Patient Health Questionnaire-9 (PHQ-9) and General Anxiety Disorder scale (GAD-7)) and health-related quality of life (EQ-5D-5L). We will measure blood pressure, height, weight and waist circumference according to WHO guidelines. We will also measure glycated haemoglobin, lipid profile, thyroid function, liver function, creatinine and haemoglobin. Prevalence rates of physical health conditions and health-risk behaviours will be presented and compared with the WHO STEPS survey findings in the general population. Regression analyses will explore the association between health-risk behaviours, mental and physical health conditions. ETHICS AND DISSEMINATION: The study has been approved by the ethics committees of the Department of Health Sciences University of York (UK), Centre for Injury Prevention and Rehabilitation (Bangladesh), Health Ministry Screening Committee and Indian Council of Medical Research (India) and National Bioethics Committee (Pakistan). Findings will be disseminated in peer-reviewed articles, in local and international conferences and as reports for policymakers and stakeholders in the countries involved. TRIAL REGISTRATION NUMBER: ISRCTN88485933; 3 June 2019.

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.

Behavioural activation therapy for depression in adults with non-communicable diseases.

BACKGROUND: Depression is common in people with non-communicable diseases (NCDs) such as cardiovascular disease, diabetes, cancer, and chronic respiratory conditions. The co-existence of depression and NCDs may affect health behaviours, compliance with treatment, physiological factors, and quality of life. This in turn is associated with worse outcomes for both conditions. Behavioural activation is not currently indicated for the treatment of depression in this population in the UK, but is increasingly being used to treat depression in adults. OBJECTIVES: To examine the effects of behavioural activation compared with any control group for the treatment of depression in adults with NCDs. To examine the effects of behavioural activation compared with each control group separately (no treatment, waiting list, other psychological therapy, pharmacological treatment, or any other type of treatment as usual) for the treatment of depression in adults with NCDs. SEARCH METHODS: We searched CCMD-CTR, CENTRAL, Ovid MEDLINE, Embase, four other databases, and two trial registers on 4 October 2019 to identify randomised controlled trials (RCTs) of behavioural activation for depression in participants with NCDs, together with grey literature and reference checking. We applied no restrictions on date, language, or publication status to the searches. SELECTION CRITERIA: We included RCTs of behavioural activation for the treatment of depression in adults with one of four NCDs: cardiovascular disease, diabetes, cancer, and chronic respiratory conditions. Only participants with a formal diagnosis of both depression and an NCD were eligible. Studies were included if behavioural activation was the main component of the intervention. We included studies with any comparator that was not behavioural activation, and regardless of reported outcomes. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane, including independent screening of titles/abstracts and full-text manuscripts, data extraction, and risk of bias assessments in duplicate. Where necessary, we contacted study authors for more information. MAIN RESULTS: We included two studies, contributing data from 181 participants to the analyses. Both studies recruited participants from US hospital clinics; one included people who were recovering from a stroke and the other women with breast cancer. For both studies, the intervention consisted of eight weeks of face-to-face behavioural therapy, with one study comparing to poststroke treatment as usual and the other comparing to problem-solving therapy. Both studies were at risk of performance bias and potential conflict of interest arising from author involvement in the development of the intervention. For one study, risks of selection bias and reporting bias were unclear and the study was judged at high risk of attrition bias. Treatment efficacy (remission) was greater for behavioural activation than for comparators in the short term (risk ratio (RR) 1.53, 95% confidence interval (CI) 0.98 to 2.38; low-certainty evidence) and medium term (RR 1.76, 95% CI 1.01 to 3.08; moderate-certainty evidence), but these estimates lacked precision and effects were reduced in the long term (RR 1.42, 95% CI 0.91 to 2.23; moderate-certainty evidence). We found no evidence of a difference in treatment acceptability in the short term (RR 1.81, 95% CI 0.68 to 4.82) and medium term (RR 0.88, 95% CI 0.25 to 3.10) (low-certainty evidence). There was no evidence of a difference in depression symptoms between behavioural activation and comparators (short term: MD -1.15, 95% CI -2.71 to 0.41; low-certainty evidence). One study found no difference for quality of life (short term: MD 0.40, 95% CI -0.16 to 0.96; low-certainty evidence), functioning (short term: MD 2.70, 95% CI -6.99 to 12.39; low-certainty evidence), and anxiety symptoms (short term: MD -1.70, 95% CI -4.50 to 1.10; low-certainty evidence). Neither study reported data on adverse effects. AUTHORS' CONCLUSIONS: Evidence from this review was not sufficient to draw conclusions on the efficacy and acceptability of behavioural activation for the treatment of depression in adults with NCDs. A future review may wish to include, or focus on, studies of people with subthreshold depression or depression symptoms without a formal diagnosis, as this may inform whether behavioural activation could be used to treat mild or undiagnosed (or both) depressive symptoms in people with NCDs. Evidence from low-resource settings including low- and middle-income countries, for which behavioural activation may offer a feasible alternative to other treatments for depression, would be of interest.

Integrating depression care within NCD provision in Bangladesh and Pakistan: a qualitative study.

BACKGROUND: Co-morbidity of depression with other non-communicable diseases (NCDs) worsens clinical outcomes for both conditions. Low- and middle-income countries need to strengthen mechanisms for detection and management of co-morbid depression within NCDs. The Behavioural Activation for Comorbid Depression in Non-communicable Disease (BEACON) study explored the acceptability and feasibility of integrating a brief depression intervention (behavioural activation, BA) into NCD services in healthcare facilities in Bangladesh and Pakistan. METHODS: Face-to-face qualitative interviews were conducted with 43 patients and 18 health workers attending or working in NCD centres in four healthcare facilities in Bangladesh and Pakistan, and with three policy makers in each country. The interviews addressed four research questions (1) how NCD care is delivered, (2) how NCD patients experience distress, (3) how depression care is integrated within NCD provision, and (4) the challenges and opportunities for integrating a brief depression intervention into usual NCD care. The data were analysed using framework analysis, organised by capability, opportunity and motivation factors, cross-synthesised across countries and participant groups. RESULTS: Patients and health workers described NCD centres as crowded and time pressured, with waiting times as long as five hours, and consultation times as short as five minutes; resulting in some patient frustration. They did not perceive direct links between their distress and their NCD conditions, instead describing worries about family and finance including affordability of NCD services. Health worker and policy maker accounts suggested these NCD centres lacked preparedness for treating depression in the absence of specific guidelines, standard screening tools, recording systems or training. Barriers and drivers to integrating a brief depression intervention reflected capability, opportunity and motivation factors for all participant groups. While generally valuing the purpose, significant challenges included the busy hospital environment, skill deficits and different conceptions of depression. CONCLUSIONS: Given current resource constraints and priorities, integrating a brief psychological intervention at these NCD centres appears premature. An opportune first step calls for responding to patients' expressed concerns on service gaps in provisioning steady and affordable NCD care. Acknowledging differences of conceptions of depression and strengthening psychologically informed NCD care will in turn be required before the introduction of a specific psychological intervention such as BA.

A process for developing a sustainable and scalable approach to community engagement: community dialogue approach for addressing the drivers of antibiotic resistance in Bangladesh.

BACKGROUND: Community engagement approaches that have impacted on health outcomes are often time intensive, small-scale and require high levels of financial and human resources. They can be difficult to sustain and scale-up in low resource settings. Given the reach of health services into communities in low income countries, the health system provides a valuable and potentially sustainable entry point that would allow for scale-up of community engagement interventions. This study explores the process of developing an embedded approach to community engagement taking the global challenge of antibiotic resistance as an example. METHODS: The intervention was developed using a sequential mixed methods study design. This consisted of: exploring the evidence base through an umbrella review, and identifying key international standards on the appropriate use of antibiotics; undertaking detailed formative research through a) a qualitative study to explore the most appropriate mechanisms through which to embed the intervention within the existing health system and community infrastructure, and to understand patterns of knowledge, attitudes and practice regarding antibiotics and antibiotic resistance; and b) a household survey - which drew on the qualitative findings - to quantify knowledge, and reported attitudes and practice regarding antibiotics and antibiotic resistance within the target population; and c) drawing on appropriate theories regarding change mechanisms and experience of implementing community engagement interventions to co-produce the intervention processes and materials with key stakeholders at policy, health system and community level. RESULTS: A community engagement intervention was co-produced and was explicitly designed to link into existing health system and community structures and be appropriate for the cultural context, and therefore have the potential to be implemented at scale. We anticipate that taking this approach increases local ownership, as well as the likelihood that the intervention will be sustainable and scalable. CONCLUSIONS: This study demonstrates the value of ensuring that a range of stakeholders co-produce the intervention, and ensuring that the intervention is designed to be appropriate for the health system, community and cultural context.

Using behaviour change theory to train health workers on tobacco cessation support for tuberculosis patients: a mixed-methods study in Bangladesh, Nepal and Pakistan.

BACKGROUND: Low- and middle-income countries (LMICs) are disproportionately impacted by interacting epidemics of tuberculosis (TB) and tobacco consumption. Research indicates behavioural support delivered by health workers effectively promotes tobacco cessation. There is, however, a paucity of training to support LMIC health workers deliver effective tobacco cessation behavioural support. The TB and Tobacco Consortium undertook research in South Asia to understand factors affecting TB health workers' delivery of tobacco cessation behavioural support, and subsequently developed a training package for LMICs. METHODS: Using the "capability, opportunity, and motivation as determinants of behaviour" (COM-B) framework to understand any issues facing health worker delivery of behaviour support, we analysed 25 semi-structured interviews and one focus group discussion with TB health workers, facility in-charges, and national tuberculosis control programme (NTP) staff members in each country. Results were integrated with findings of an adapted COM-B questionnaire on health worker confidence in tobacco cessation support delivery, administered to 36 TB health workers. Based on findings, we designed a guide and training programme on tobacco cessation support for health workers. RESULTS: Qualitative results highlighted gaps in the majority of health workers' knowledge on tobacco cessation and TB and tobacco interaction, inadequate training on patient communication, insufficient resources and staff support, and NTPs' non-prioritization of tobacco cessation in all three countries. Questionnaire results reiterated the knowledge deficits and low confidence in patient communication. Participants suggested strengthening knowledge, skills, and competence through training and professional incentives. Based on findings, we developed an interactive two-day training and TB health worker guide adaptable for LMICs, focusing on evidence of best practice on TB and tobacco cessation support, communication, and rapport building with patients. CONCLUSIONS: TB health workers are essential in addressing the dual burden of TB and tobacco faced by many LMICs. Factors affecting their delivery of tobacco cessation support can be identified using the COM-B framework, and include issues such as individuals' knowledge and skills, as well as structural barriers like professional support through monitoring and supervision. While structural changes are needed to tackle the latter, we have developed an adaptable and engaging health worker training package to address the former that can be delivered in routine TB care. TRIAL REGISTRATION: ISRCTN43811467 .

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.

"He Doesn't Listen to My Words at All, So I Don't Tell Him Anything"-A Qualitative Investigation on Exposure to Second Hand Smoke among Pregnant Women, Their Husbands and Family Members from Rural Bangladesh and Urban India.

Second hand smoke (SHS) exposure during pregnancy is associated with poor pregnancy and fetal outcomes. To design interventions to reduce exposure, an in depth understanding of social and cultural factors of smoking behavior at home is important, especially in South Asia where SHS exposure is high. This study aimed to explore pregnant women's, their husbands' and other family members' knowledge, attitudes and practices regarding home SHS exposure. Semi-structured interviews were conducted with 33 participants in Comilla, Bangladesh and 31 in Bangalore, India (36 pregnant women, 18 husbands, and 10 family members). Data were analyzed using the Framework approach. Husbands smoked in various living areas inside the home, often in the presence of their pregnant wives. Most had never tried to stop smoking at home. Knowledge of the risks was generally poor. Most women had repeatedly asked their husband to smoke outside with little success and only few family members had reprimanded the husbands. Husbands who had stopped did so because of requests from children and their mother. Potential strategies to decrease SHS exposure at home were educating the husband about risks and supporting the pregnant women in negotiation. Interventions must also enlist family support to enhance the woman's self-efficacy.