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Chunrui Zou,1,2 Frank Li,2,3 Jiwoong Choi,1,4 Babak Haghighi,5 Sanghun Choi,6 Prathish K Rajaraman,1,2 Alejandro P Comellas,7 John D Newell Jnr,8 Chang Hyun Lee,8,9 R Graham Barr,10 Eugene Bleecker,11 Christopher B Cooper,12 David Couper,13 Meilan Han,14 Nadia N Hansel,15 Richard E Kanner,16 Ella A Kazerooni,17 Eric C Kleerup,18 Fernando J Martinez,19 Wanda O’Neal,20 Robert Paine III,16 Stephen I Rennard,21 Benjamin M Smith,22,23 Prescott G Woodruff,24 Eirc A Hoffman,3,7,8 Ching-Long Lin1– 3,8 1Department of Mechanical Engineering, University of Iowa, Iowa City, IA, USA; 2IIHR-Hydroscience & Engineering, University of Iowa, Iowa City, IA, USA; 3Department of Biomedical Engineering, University of Iowa, Iowa City, IA, USA; 4Department of Internal Medicine, School of Medicine, University of Kansas, Kansas City, KS, USA; 5Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 6School of Mechanical Engineering, Kyungpook National University, Daegu, Republic of Korea; 7Department of Internal Medicine, University of Iowa, Iowa City, IA, USA; 8Department of Radiology, University of Iowa, Iowa City, IA, USA; 9Department of Radiology, College of Medicine, Seoul National University, Seoul, Republic of Korea; 10Mailman School of Public Health, Columbia University, New York, NY, USA; 11Department of Medicine, The University of Arizona, Tucson, AZ, USA; 12Department of Physiology, UCLA, Los Angeles, CA, USA; 13Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA; 14Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; 15School of Medicine, Johns Hopkins, Baltimore, MD, USA; 16School of Medicine, University of Utah, Salt Lake City, UT, USA; 17Department of Radiology, University of Michigan, Ann Arbor, MI, USA; 18Department of Medicine, UCLA, Los Angeles, CA, USA; 19Weill Cornell Medicine, Cornell University, New York, NY, USA; 20School of Medicine, University of North Carolina, Chapel Hill, NC, USA; 21Department of Internal Medicine, University of Nebraska College of Medicine, Omaha, NE, USA; 22Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA; 23Department of Medicine, McGill University Health Centre Research Institute, Montreal, Canada; 24Department of Medicine, University of California at San Francisco, San Francisco, CA, USACorrespondence: Ching-Long Lin 2406 Seamans Center for the Engineering Art and Science, Iowa City, IA, 52242, USATel +1 319 335 5673Email ching-long-lin@uiowa.eduPurpose: Quantitative computed tomography (qCT) imaging-based cluster analysis identified clinically meaningful COPD former-smoker subgroups (clusters) based on cross-sectional data. We aimed to identify progression clusters for former smokers using longitudinal data.Patients and Methods: We selected 472 former smokers from SPIROMICS with a baseline visit and a one-year follow-up visit. A total of 150 qCT imaging-based variables, comprising 75 variables at baseline and their corresponding progression rates, were derived from the respective inspiration and expiration scans of the two visits. The COPD progression clusters identified were then associated with subject demography, clinical variables and biomarkers.Results: COPD severities at baseline increased with increasing cluster number. Cluster 1 patients were an obese subgroup with rapid progression of functional small airway disease percentage (fSAD%) and emphysema percentage (Emph%). Cluster 2 exhibited a decrease of fSAD% and Emph%, an increase of tissue fraction at total lung capacity and airway narrowing over one year. Cluster 3 showed rapid expansion of Emph% and an attenuation of fSAD%. Cluster 4 demonstrated severe emphysema and fSAD and significant structural alterations at baseline with rapid progression of fSAD% over one year. Subjects with different progression patterns in the same cross-sectional cluster were identified by longitudinal clustering.Conclusion: qCT imaging-based metrics at two visits for former smokers allow for the derivation of four statistically stable clusters associated with unique progression patterns and clinical characteristics. Use of baseline variables and their progression rates enables identification of longitudinal clusters, resulting in a refinement of cross-sectional clusters.Keywords: computed tomography, emphysema, functional small airway disease, longitudinal clustering

Objectives To implement and evaluate a public-private partnership to deliver the internationally recommended strategy DOTS for the control of tuberculosis (TB) in Lalitpur municipality, Nepal, where it is estimated that 50% of patients with TB are managed in the private sector. Methods A local working group developed a public-private partnership for control of TB, which included diagnosis by private practitioners, direct observation of treatment and tracing of patients who missed appointments by nongovernmental organizations, and provision of training and drugs by the Nepal National TB Programme (NTP). The public-private partnership was evaluated through baseline and follow-up surveys of private practitioners, private pharmacies, and private laboratories, together with records kept by the Nepal NTR Findings In the first 36 months, 1328 patients with TB were registered in the public-private partnership. Treatment success rates were >90%, and <1% of patients defaulted. Case notification of sputum-positive patients in the study area increased from 54 per 100 000 to 102 per 100 000. The numbers of patients with TB started on treatment by private practitioners decreased by more than two-thirds, the number of private pharmacies that stocked anti-TB drugs by one-third, the number of pharmacies selling anti-TB drugs by almost two-thirds, and sales of anti-TB drugs in pharmacies by almost two-thirds. Private practitioners were happy to refer patients to the public-private partnership. Not all private practitioners had to be involved: many patients bypassed private 'practitioners and went directly to free DOTS centres. Conclusions A combination of the strengths of private practitioners, nongovernmental organizations, and the public sector in a public-private partnership can be used to provide a service that is liked by patients and gives high rates of treatment success and increased rates of patient notification. Similar public-private partnerships are likely to be replicable elsewhere, as inputs are not large and no special requirements exist. [ABSTRACT FROM AUTHOR]

Background: Although malaria is known to be a major cause of child mortality and morbidity throughout sub-Saharan Africa there are few detailed studies of malaria mortality rates and incidence of severe malarial disease in defined communities. We have studied the geographical pattern of admissions to hospital with severe malaria and the stability of this pattern over time in Kilifi District on the Kenyan Coast.Methods: Over a 2-year period all children under 5 years of age with severe malaria admitted to the district hospital and living in a rural study population of about 50,000 people were identified. Annual censuses were carried out in the study area, and all households were mapped using a hand-held satellite navigation system. The resulting databases were linked using a geographical information system (GIS).Results: Using methods originally developed for the study of the geographical distribution of childhood leukaemia we assessed the spatial pattern of hospital admission rates for severe malaria. As expected, admission rates were significantly higher in children with easier access to the hospital. For example, those living more than 25 km from the hospital had admission rates which were about one-fifth of those for children living within 5 km of the hospital. Those living more than 2.5 km from the nearest road had admission rates that were about half of those for children living within 0.5 km of a road. We also investigated short-term local fluctuations in severe malaria and found evidence of space-time clustering of severe malaria.Conclusions: Hospital admission rates for severe malaria are higher in households with better access to hospital than in those further away. The finding of space-time clusters of severe malaria suggests that it would be of value to conduct case-control studies of environmental, genetic and human behavioural factors involved in the aetiology of the disease. [ABSTRACT FROM AUTHOR]

Background: In the new Stop TB Strategy for Tuberculosis (TB) Care, direct observation of treatment has been replaced by "supervision and patient support". However, it is still unclear what patient support means and how it is to be best implemented. The objective of this study was to accurately document patients' support needs during TB treatment from their own perspectives, to inform development of appropriate support and supervision strategies that meet patients' needs.Methods: In-depth individual interviews and focus group discussions were conducted in three districts in Nepal. Analysis took place concurrently with data collection to allow emerging issues to guide selection of subsequent interviewees. In total 23 patients, 15 male and 8 female, were interviewed and six focus group discussions were held. Issues from these interviews were grouped into emergent themes.Results: Respondents reported that the burden of treatment for TB was high, particularly in terms of difficulties with social and psychological aspects of undergoing treatment. They saw three main areas for support during their treatment: relevant information for them and their families about their disease, its treatment, potential side-effects and what they should do if side-effects arise; approachable and supportive healthcare staff with whom patients feel comfortable discussing (often non-medical) problems that arise during treatment; and some flexibility in treatment to allow essential elements of patients' lives (such as income generation, food-growing and childcare) to continue. They were anxious to ensure that family support did not absolve healthcare workers from their own support responsibilities.Conclusion: In order to support people with TB more during their treatment, health policy and practice must appreciate that TB affects all aspects of TB patients' lives. A focus on caring for each patient as an individual should underlie all aspects of treatment. Improved communication between healthcare providers and patients and increased patient knowledge and understanding of the treatment programme would give those receiving treatment a sense of individual empowerment and raise their confidence in treatment. [ABSTRACT FROM AUTHOR]

What role does visual experience play in the development of object recognition? Prior controlled-rearing studies suggest that newborn animals require slow and smooth visual experiences to develop object recognition. Here, we examined whether the development of object recognition also requires experience with the surface features of objects. We raised newborn chicks in automated controlled-rearing chambers that contained a single virtual object, then tested their ability to recognize that object from familiar and novel viewpoints. When chicks were reared with an object that had surface features, the chicks developed view-invariant object recognition. In contrast, when chicks were reared with a line drawing of an object, the chicks failed to develop object recognition. The chicks reared with line drawings performed at chance level, despite acquiring over 100 h of visual experience with the object. These results indicate that the development of object recognition requires experience with the surface features of objects.

Objective: To assess the effect of rural-to-urban migration on nutrition transition and overweight/obesity risk among women in Kenya., Design: Secondary analysis of data from nationally representative cross-sectional samples. Outcome variables were women's BMI and nutrition transition. Nutrition transition was based on fifteen different household food groups and was adjusted for socio-economic and demographic characteristics. Stepwise backward multiple ordinal regression analysis was applied., Setting: Kenya Demographic and Health Survey 2014., Participants: Rural non-migrant, rural-to-urban migrant and urban non-migrant women aged 15-49 years (n 6171)., Results: Crude data analysis showed rural-to-urban migration to be associated with overweight/obesity risk and nutrition transition. After adjustment for household wealth, no significant differences between rural non-migrants and rural-to-urban migrants for overweight/obesity risk and household consumption of several food groups characteristic of nutrition transition (animal-source, fats and sweets) were observed. Regardless of wealth, migrants were less likely to consume main staples and legumes, and more likely to consume fruits and vegetables. Identified predictive factors of overweight/obesity among migrant women were age, duration of residence in urban area, marital status and household wealth., Conclusions: Our analysis showed that nutrition transition and overweight/obesity risk among rural-to-urban migrants is apparent with increasing wealth in urban areas. Several predictive factors were identified characterising migrant women being at risk for overweight/obesity. Future research is needed which investigates in depth the association between rural-to-urban migration and wealth to address inequalities in diet and overweight/obesity in Kenya.

Loss to follow-up (LFU) of ≥2 consecutive months contributes to the poor levels of treatment success in multidrug-resistant tuberculosis (MDR-TB) reported by TB programmes. We explored the timing of when LFU occurs by month of MDR-TB treatment and identified patient-level risk factors associated with LFU.We analysed a dataset of individual MDR-TB patient data (4099 patients from 22 countries). We used Kaplan-Meier survival curves to plot time to LFU and a Cox proportional hazards model to explore the association of potential risk factors with LFU.Around one-sixth (n=702) of patients were recorded as LFU. Median (interquartile range) time to LFU was 7 (3-11) months. The majority of LFU occurred in the initial phase of treatment (75% in the first 11 months). Major risk factors associated with LFU were: age 36-50 years (HR 1.3, 95% CI 1.0-1.6; p=0.04) compared with age 0-25 years, being HIV positive (HR 1.8, 95% CI 1.2-2.7; p<0.01) compared with HIV negative, on an individualised treatment regimen (HR 0.7, 95% CI 0.6-1.0; p=0.03) compared with a standardised regimen and a recorded serious adverse event (HR 0.5, 95% CI 0.4-0.6; p<0.01) compared with no serious adverse event.Both patient- and regimen-related factors were associated with LFU, which may guide interventions to improve treatment adherence, particularly in the first 11 months., Competing Interests: Conflict of interest: I.F. Walker reports grants from DFID, UK Government, during the conduct of the study. Conflict of interest: O. Shi has nothing to disclose. Conflict of interest: J.P. Hicks has nothing to disclose. Conflict of interest: H. Elsey has nothing to disclose. Conflict of interest: X. Wei has nothing to disclose. Conflict of interest: D. Menzies has nothing to disclose. Conflict of interest: Z. Lan has nothing to disclose. Conflict of interest: D. Falzon has nothing to disclose. Conflict of interest: G.B. Migliori has nothing to disclose. Conflict of interest: C. Pérez-Guzmán has nothing to disclose. Conflict of interest: M.H. Vargas has nothing to disclose. Conflict of interest: L. García-García has nothing to disclose. Conflict of interest: J. Sifuentes Osornio has nothing to disclose. Conflict of interest: A. Ponce-De-León has nothing to disclose. Conflict of interest: M. van der Walt has nothing to disclose. Conflict of interest: J.M. Newell has nothing to disclose., (Copyright ©ERS 2019.)

In a qualitative study on the stigma associated with tuberculosis (TB), involving 73 interviews and eight focus groups conducted in five sites across three countries (Bangladesh, Nepal, and Pakistan), participants spoke of TB's negative impact on the marriage prospects of women in particular. Combining the approach to discovering grounded theory with a conceptualization of causality based on a realist ontology, we developed a theory to explain the relationships between TB, gender, and marriage. The mechanism at the heart of the theory is TB's disruptiveness to the gendered roles of wife (or daughter-in-law) and mother. It is this disruptiveness that gives legitimacy to the rejection of marriage to a woman with TB. Whether or not this mechanism results in a negative impact of TB on marriage prospects depends on a range of contextual factors, providing opportunities for interventions and policies.

Setting: Multidrug-resistant tuberculosis (MDR-TB) patients in the national TB treatment programme of Nepal., Objective: To estimate the prevalence of depression and anxiety in people receiving treatment for MDR-TB, identify potential risk factors for depression and anxiety and determine temporal changes in their severity during treatment., Design: An observational study using a screening tool, the Hopkins Symptom Checklist (HSCL-25) for depression and anxiety, administered monthly to a group of 135 patients in Nepal. Logistic and multilevel linear regression models were used to identify any patient characteristics associated with depression and anxiety., Results: Most of the 135 patients were male (76%) and living with their families (68%). The period prevalences of depression and anxiety were respectively 22.2% and 15.6%. Patients reporting physical side effects of MDR-TB treatment had a higher depression score on HSCL by 2.63 points (95%CI 0.77-4.48) and a 1.59 point higher anxiety score (95%CI 0.45-2.73) than those who did not report any side effects. Being single was associated with having anxiety (aOR 0.2, 95%CI 0.03-1.0)., Conclusion: Given the high rates of depression observed among MDR-TB patients, national TB treatment programmes should ensure their patients are routinely screened for depression and anxiety, and effective treatment offered., Competing Interests: Conflicts of interest: none declared.

Background: The Community Dialogue Approach is a promising social and behaviour change intervention, which has shown potential for improving health seeking behaviour. To test if this approach can strengthen prevention and control of schistosomiasis at community level, Malaria Consortium implemented a Community Dialogue intervention in four districts of Nampula province, Mozambique, between August 2014 and September 2015., Methodology/principal Findings: Cross-sectional household surveys were conducted before (N = 791) and after (N = 792) implementation of the intervention to assess its impact on knowledge, attitudes and practices at population level. At both baseline and endline, awareness of schistosomiasis was high at over 90%. After the intervention, respondents were almost twice as likely to correctly name a risk behaviour associated with schistosomiasis (baseline: 18.02%; endline: 30.11%; adjusted odds ratio: 1.91; 95% confidence interval: 1.14-2.58). Increases were also seen in the proportion of people who knew that schistosomiasis can be spread by infected persons and who could name at least one correct transmission route (baseline: 25.74%; endline: 32.20%; adjusted odds ratio: 1.36; 95% confidence interval: 1.01-1.84), those who knew that there is a drug that treats the disease (baseline: 29.20%, endline: 47.55%; adjusted odds ratio: 2.19; 95% confidence interval: 1.67-2.87) and those who stated that they actively protect themselves from the disease and cited an effective behaviour (baseline: 40.09%, endline: 59.30%; adjusted odds ratio: 2.14; 95% confidence interval: 1.40-3.28). The intervention did not appear to lead to a reduction in misconceptions. In particular, the belief that the disease is sexually transmitted continued to be widespread., Conclusions/significance: Given its overall positive impact on knowledge and behaviour at population level, Community Dialogue can play an important role in schistosomiasis prevention and control. The intervention could be further strengthened by better enabling communities to take suitable action and linking more closely with community governance structures and health system programmes., Competing Interests: The authors have declared that no competing interests exist.

Background: Inappropriate antibiotic prescribing causes widespread serious health problems. To reduce prescribing of antibiotics in Chinese primary care to children with upper respiratory tract infections (URTIs), we developed an intervention comprising clinical guidelines, monthly prescribing review meetings, doctor-patient communication skills training, and education materials for caregivers. We previously evaluated our intervention using an unblinded cluster-randomised controlled trial (cRCT) in 25 primary care facilities across two rural counties. When our trial ended at the 6-month follow-up period, we found that the intervention had reduced antibiotic prescribing for childhood URTIs by 29 percentage points (pp) (95% CI -42 to -16)., Methods and Findings: In this long-term follow-up study, we collected our trial outcomes from the one county (14 facilities and 1:1 cluster randomisation ratio) that had electronic records available 12 months after the trial ended, at the 18-month follow-up period. Our primary outcome was the antibiotic prescription rate (APR)-the percentage of outpatient prescriptions containing any antibiotic(s) for children aged 2 to 14 years who had a primary diagnosis of a URTI and had no other illness requiring antibiotics. We also conducted 15 in-depth interviews to understand how interventions were sustained. In intervention facilities, the APR was 84% (1,171 out of 1,400) at baseline, 37% (515 out of 1,380) at 6 months, and 54% (2,748 out of 5,084) at 18 months, and in control facilities, it was 76% (1,063 out of 1,400), 77% (1,084 out of 1,400), and 75% (2,772 out of 3,685), respectively. After adjusting for patient and prescribing doctor covariates, compared to the baseline intervention-control difference, the difference at 6 months represented a 6-month intervention-arm reduction in the APR of -49 pp (95% CI -63 to -35; P < 0.0001), and compared to the baseline difference, the difference at 18 months represented an 18-month intervention-arm reduction in the APR of -36 pp (95% CI -55 to -17; P < 0.0001). Compared to the 6-month intervention-control difference, the difference at 18 months represented no change in the APR: 13 pp (95% CI -7 to 33; P = 0.21). Factors reported to sustain reductions in antibiotic prescribing included doctors' improved knowledge and communication skills and focused prescription review meetings, whereas lack of supervision and monitoring may be associated with relapse. Key limitations were not including all clusters from the trial and not collecting returned visits or sepsis cases., Conclusions: Our intervention was associated with sustained and substantial reductions in antibiotic prescribing at the end of the intervention period and 12 months later. Our intervention may be adapted to similar resource-poor settings., Trial Registration: ISRCTN registry ISRCTN14340536., Competing Interests: The authors have declared that no competing interests exist.

Introduction: As rapid urbanisation transforms the sociodemographic structures within cities, standard survey methods, which have remained unchanged for many years, under-represent the urban poorest. This leads to an overly positive picture of urban health, distorting appropriate allocation of resources between rural and urban and within urban areas. Here, we present a protocol for our study which (i) tests novel methods to improve representation of urban populations in household surveys and measure mental health and injuries, (ii) explores urban poverty and compares measures of poverty and 'slumness' and (iii) works with city authorities to understand, and potentially improve, utilisation of data on urban health for planning more equitable services., Methods and Analysis: We will conduct household surveys in Kathmandu, Hanoi and Dhaka to test novel methods: (i) gridded population sampling; (ii) enumeration using open-access online maps and (iii) one-stage versus two-stage cluster sampling. We will test reliability of an observational tool to categorise neighbourhoods as slum areas. Within the survey, we will assess the appropriateness of a short set of questions to measure depression and injuries. Questionnaire data will also be used to compare asset-based, consumption-based and income-based measures of poverty. Participatory methods will identify perceptions of wealth in two communities in each city. The analysis will combine quantitative and qualitative findings to recommend appropriate measures of poverty in urban areas. We will conduct qualitative interviews and establish communities of practice with government staff in each city on use of data for planning. Framework approach will be used to analyse qualitative data allowing comparison across city settings., Ethics and Dissemination: Ethical approvals have been granted by ethics committees from the UK, Nepal, Bangladesh and Vietnam. Findings will be disseminated through conference papers, peer-reviewed open access articles and workshops with policy-makers and survey experts in Kathmandu, Hanoi and Dhaka., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.)

Background: Almost three quarters of non-communicable disease (NCD) deaths, and 82% of premature NCD deaths, occur in low- and middle-income countries. Bangladesh has an estimated 7 million hypertensives and 10 million diabetics, and primary care is struggling to respond. Our aim was to develop and support implementation of a diabetes and hypertension case management package, and assess its appropriateness, feasibility and acceptability in two NCD clinics within two primary-care centres in Bangladesh., Methods: We used a convergent mixed methods design. We first assessed the level of appropriate hypertension and cardiovascular disease patient management, based on a composite outcome indicator using data from patients' treatment cards. Appropriate management was primarily informed by International Diabetes Federation (IDF) and World Health Organisation (WHO) guidelines. We then performed qualitative in-depth interviews with doctors and patients to explain these quantitative findings and to understand the challenges to achieving appropriate patient management in the NCD clinics., Results: Eighty-one newly diagnosed patients were recruited. Over 3 months, 53.1% (95% CI 42.3% to 63.6%) of patients were appropriately managed. We found incomplete diagnosis (especially missing hypertension diagnosis alongside diabetes) and non-provision of follow-up appointments were the main causes of the relatively low level of appropriate management. We conducted interviews with 11 patients and 8 health professionals and found a shortage of human resources, reporting materials, available drugs and diagnostic equipment. This undermined patients' willingness to attend clinics and doctors' willingness to offer follow-ups. Hands-on skill-building training was valuable in increasing doctors' competence for appropriate management, but was seen as a novel training method and faced constraints to implementation., Conclusions: A clinical guide, skill-based training and recording package can be implemented in routine primary care and can lead to appropriate management of around half of diabetic and hypertensive patients in a low-income country. However, considerable health systems challenges must be addressed before more patients can be managed appropriately.

Introduction: eHealth solutions that use internet and related technologies to deliver and enhance health services and information are emerging as novel approaches to support healthcare delivery in sub-Saharan Africa. Using digital technology in this way can support cost-effectiveness of care delivery and extend the reach of services to remote locations. Despite the burgeoning literature on eHealth approaches, little is known about the effectiveness of eHealth tools for improving the quality and efficiency of health systems functions or client outcomes in resource-limited countries. eHealth tools including satellite communications are currently being implemented at scale, to extend health services to rural areas of Nigeria, in Ondo and Kano States and the Federal Capital Territory. This paper shares the protocol for a 2-year project ('EXTEND') that aims to evaluate the impact of eHealth tools on health system functions and health outcomes., Methodology and Analysis: This multisite, mixed-method evaluation includes a non-randomised, cluster trial design. The study comprises three phases-baseline, midline and endline evaluations-that involve: (1) process evaluation of video training and digitisation of health data interventions; (2) evaluation of contextual influences on the implementation of interventions; and (3) impact evaluation of results of the project. A convergent mixed-method model will be adopted to allow integration of quantitative and qualitative findings to achieve study objectives. Multiple quantitative and qualitative datasets will be repeatedly analysed and triangulated to facilitate better understanding of impact of eHealth tools on health worker knowledge, quality and efficiency of health systems and client outcomes., Ethics and Dissemination: Ethics approvals were obtained from the University of Leeds and three States' Ministries of Health in Nigeria. All data collected for this study will be anonymised and reports will not contain information that could identify respondents. Study findings will be presented to Ministries of Health at scientific conferences and published in peer-reviewed journals., Trial Registration Number: ISRCTN32105372; Pre-results., Competing Interests: Competing interests: OO is Co-Founder and CEO of InStrat Global Health Solutions, the company that will implement the eHealth tools used in the outlined research programme. TO is Programme Director and TJ a development consultant for Inmarsat, the company providing satellite communication capability to deliver eHealth tools during the research programme. All other authors declare having no competing interests (BE, MA, BO, GA, JT, KO, DA, AA, OD, RY, JH, AIS, TM and JM)., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: People receiving treatment for multidrug-resistant tuberculosis (MDR-TB) have high rates of depression. Psychosocial support in general, and treatments for depression in particular, form an important but neglected area of patient-centred care, and a key pillar in the global End TB strategy. We assessed the feasibility and acceptability of a psychosocial support package for people receiving treatment for MDR-TB in Nepal., Methods: This feasibility study used a mixed quantitative and qualitative approach. We implemented the intervention package in two National Tuberculosis Programme (NTP) MDR-TB treatment centres and 8 sub-centres. We screened patients monthly for depression and anxiety (cut-off ≥24 and ≥17 respectively on the Hopkins Symptom Checklist) and also for low social support (cut-off ≤3 on the Multidimensional Scale of Perceived Social Support). Those who screened positive on either screening tool received the Healthy Activity Program (HAP), which uses brief counselling based on behavioural activation theory. Other aspects of the psychosocial package were information/education materials and group interactions with other patients., Results: We screened 135 patients, of whom 12 (9%) received HAP counselling, 115 (85%) received information materials, 80 (59%) received an education session and 49 (36%) received at least one group session. Eight group sessions were conducted in total. All aspects of the intervention package were acceptable to patients, including the screening, information, group work and counselling. Patients particularly valued having someone to talk to about their concerns and worries. We were able to successfully train individuals with no experience of psychological counselling to deliver HAP., Conclusion: This psychosocial support package is acceptable to patients. The information materials we developed are feasible to deliver in the current NTP. However, the structured psychological counselling (HAP), is not feasible in the current NTP due to time constraints. This requires additional investment of counsellors in TB clinics., Competing Interests: The authors have declared that no competing interests exist.

Background: The role of non-governmental organisations (NGOs) in health research has attracted growing attention. NGOs are important service providers and advocates in international health, and conducting research can help NGOs to strengthen these service delivery and advocacy activities. However, capacity to conduct research varies among NGOs. There is currently limited evidence on NGOs' research capacity that can explain why capacity varies or indicate potential areas for support. We examined NGOs' capacity to conduct research, identifying factors that affect their access to the funds, time and skills needed to undertake research., Methods: We examined research capacity through qualitative case studies of three NGOs in Malawi, including one national and two international NGOs. Data were generated through interviews and focus groups with NGO staff, observation of NGO activities, and document reviews., Results: Availability of funding, skills and time to conduct research varies considerably between the case NGOs. Access to these resources is affected by internal processes such as sources of funding and prioritisation of research, and by the wider environment and external relationships, including the nature of donor support. Constraints include limited ability to apply for research funding, a perception that donors will not support research costs, lack of funding to hire or train research staff, and prioritisation of service delivery over research in funding proposals and staff schedules., Conclusion: The findings suggest strategies for NGOs and for donors interested in supporting NGOs' research capacity. Above all, the findings reinforce the importance of initial capacity assessments to identify organisational needs and opportunities. In addition, the need for time and funding as well as skills suggests that strengthening NGOs' research capacity will often require more than research training., Competing Interests: The authors have declared that no competing interests exist.

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., (© 2018 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: Inappropriate antibiotic prescribing contributes to the generation of drug resistance worldwide, and is particularly common in China. We assessed the effectiveness of an antimicrobial stewardship programme aiming to reduce inappropriate antibiotic prescribing in paediatric outpatients by targeting providers and caregivers in primary care hospitals in rural China., Methods: We did a pragmatic, cluster-randomised controlled trial with a 6-month intervention period. Clusters were primary care township hospitals in two counties of Guangxi province in China, which were randomly allocated to the intervention group or the control group (in a 1:1 ratio in Rong county and in a 5:6 ratio in Liujiang county). Randomisation was stratified by county. Eligible participants were children aged 2-14 years who attended a township hospital as an outpatient and were given a prescription following a primary diagnosis of an upper respiratory tract infection. The intervention included clinician guidelines and training on appropriate prescribing, monthly prescribing peer-review meetings, and brief caregiver education. In hospitals allocated to the control group, usual care was provided, with antibiotics prescribed at the individual clinician's discretion. Patients were masked to their allocated treatment group but doctors were not. The primary outcome was the antibiotic prescription rate in children attending the hospitals, defined as the cluster-level proportion of prescriptions for upper respiratory tract infections in 2-14-year-old outpatients, issued during the final 3 months of the 6-month intervention period (endline), that included one or more antibiotics. The outcome was based on prescription records and analysed by modified intention-to-treat. This study is registered with the ISRCTN registry, number ISRCTN14340536., Findings: We recruited all 25 eligible township hospitals in the two counties (14 hospitals in Rong county and 11 in Liujiang county), and randomly allocated 12 to the intervention group and 13 to the control group. We implemented the intervention in three internal pilot clusters between July 1, 2015, and Dec 31, 2015, and in the remaining nine intervention clusters between Oct 1, 2016 and March 31, 2016. Between baseline (the 3 months before implementation of the intervention) and endline (the final 3 months of the 6-month intervention period) the antibiotic prescription rate at the individual level decreased from 82% (1936/2349) to 40% (943/2351) in the intervention group, and from 75% (1922/2548) to 70% (1782/2552) in the control group. After adjusting for the baseline antibiotic prescription rate, stratum (county), and potentially confounding patient and prescribing doctor covariates, this endline difference between the groups represented an intervention effect (absolute risk reduction in antibiotic prescribing) of -29% (95% CI -42 to -16; p=0·0002)., Interpretation: In China's primary care setting, pragmatic interventions on antimicrobial stewardship targeting providers and caregivers substantially reduced prescribing of antibiotics for childhood upper respiratory tract infections., Funding: Department of International Development (UKAID) through Communicable Diseases Health Service Delivery., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: This study aims to assess whether a standard intervention package of cardiovascular disease (CVD) care was being delivered effectively, and if it was associated with improved lifestyle and biomedical indicators., Methods: In rural China, we implemented a pragmatic cluster randomized controlled trial for 12 months, randomized at the township hospital level, and compared with usual care. Intervention case management guideline, training and performance monitoring meeting and patient support activities were designed to fit within the job description of family doctors in the township hospitals and comprised: 1) prescription of a standardised package of medicines targeted at those with hypertension or diabetes; 2) advice about specific lifestyle interventions; and 3) advice about medication adherence. Participants were 50-74 years old, had hypertension and CVD risk scores >20% or diabetes, but were excluded if a history of severe CVD events. We also randomly selected 100 participants from six selected clusters per arm as a panel to collect intermediate biomedical indicators over time., Results: A total of 28,130 participants, in 33 intervention and 34 control township hospitals, were recruited. Compared with the control arm, participants in the intervention arm had substantially improved prescribing rates of anti-hypertensives, statins and aspirin (P<0.001), and had higher medication taking rates of aspirin and statins (P<0.001). Mean systolic and diastolic blood pressures were similar across both arms (0.15 mmHg, P = 0.79, and 0.52 mmHg, P = 0.05, respectively). In the panel, (950) rates of smoking (OR = 0.23, P = 0.02) and salt intake (OR = 2.85, P = 0.03) were significantly reduced in the intervention versus control arms, but there were no statistically significant improvement over the 12 month follow-up period in biomedical indicators (P>0.05)., Conclusion: Implementation of the package by family doctors was feasible and improved prescribing and some lifestyle changes. Additional measures such as reducing medication costs and patient education are required., Trial Registration: Current Controlled Trials ISRCTN58988083.

The successful treatment of multidrug-resistant tuberculosis (MDR-TB) is a global health priority and a key pillar of the World Health Organization's (WHO's) End TB strategy. There has been significant global investment in diagnostic capabilities in recent years. However, we argue that the mental distress of those with MDR-TB and their families continues to be overlooked by TB programmes. Priorities in the End TB Strategy of 'patient-centred care' and 'patient support' are still to be delivered in practice in many low-income settings, and in particular consideration of mental distress. Our experience of undertaking MDR-TB operational research in China, Pakistan, Bangladesh, Nepal and Swaziland has given us detailed insight into the challenges facing patients, their families, health professionals and wider health systems. We are increasingly concerned that psychosocial support, and particularly support focused on mental health, is being insufficiently addressed in national MDR-TB programmes. We suggest that the presence of comorbid mental disorders reduces treatment adherence. We recommend the trialling within TB programmes of brief screening tools for common mental disorders and the incorporation of principles from the WHO Mental Health Gap Action Programme programme into TB programme treatment guidance. Our work in Nepal also suggests that brief psychological counselling delivered by non-specialist counsellors may be feasible.

Multi-drug-resistant tuberculosis (MDR-TB) poses a major threat to public health worldwide, particularly in low-income countries. The current long (20 month) and arduous treatment regime uses powerful drugs with side-effects that include mental ill-health. It has a high loss-to-follow-up (25%) and higher case fatality and lower cure-rates than those with drug sensitive tuberculosis (TB). While some national TB programmes provide small financial allowances to patients, other aspects of psychosocial ill-health, including iatrogenic ones, are not routinely assessed or addressed. We aimed to develop an intervention to improve psycho-social well-being for MDR-TB patients in Nepal. To do this we conducted qualitative work with MDR-TB patients, health professionals and the National TB programme (NTP) in Nepal. We conducted semi-structured interviews (SSIs) with 15 patients (10 men and 5 women, aged 21 to 68), four family members and three frontline health workers. In addition, three focus groups were held with MDR-TB patients and three with their family members. We conducted a series of meetings and workshops with key stakeholders to design the intervention, working closely with the NTP to enable government ownership. Our findings highlight the negative impacts of MDR-TB treatment on mental health, with greater impacts felt among those with limited social and financial support, predominantly married women. Michie et al's (2011) framework for behaviour change proved helpful in identifying corresponding practice- and policy-level changes. The findings from this study emphasise the need for tailored psycho-social support. Recent work on simple psychological support packages for the general population can usefully be adapted for use with people with MDR-TB., Competing Interests: The authors have declared that no competing interests exist.

Background: Seasonal Malaria Chemoprevention (SMC) is currently recommended for children under five in areas where malaria transmission is highly seasonal. We explored children's caregivers' and community health workers' (CHWs) responses to an extended 5-month SMC programme., Methods: Thirteen in-depth interviews and eight focus group discussions explored optimal and suboptimal 'uptake' of SMC to examine facilitators and barriers to caregivers' uptake., Results: There did not appear to be major differences between caregivers of children with optimal and sub-optimal SMC uptake in terms of their knowledge of malaria, their perceptions of the effect of SMC on a child's health, nor their understanding of chemoprevention. Caregivers experienced difficulty in prioritising SMC for well children, perceiving medication being for treatment rather than prevention. Prior to the study, caregivers had become accustomed to rapid diagnostic testing (RDT) for malaria, and therefore blood testing for malaria during the baseline survey at the start of the SMC programme may have positively influenced uptake. Facilitators of uptake included caregivers' trust in and respect for administrators of SMC (including CHWs), access to medication and supportive (family) networks. Barriers to uptake related to poor communication of timings of community gatherings, travel distances, absence during SMC home deliveries, and limited demand for SMC due to lack of previous experience. Future delivery of SMC by trained CHWs would be acceptable to caregivers., Conclusion: A combination of caregivers' physical access to SMC medication, the drug regimen, trust in the medical profession and perceived norms around malaria prevention all likely influenced caregivers' level of uptake. SMC programmes need to consider: 1) developing supportive, accessible and flexible modes of drug administration including home delivery and village community kiosks; 2) improving demand for preventive medication including the harnessing of learnt trust; and 3) developing community-based networks for users to support optimal uptake of SMC., Competing Interests: The authors have declared that no competing interests exist.

Background: By 2030, 80 % of the annual 8.3 million deaths attributable to tobacco will be in low-income countries (LICs). Yet, services to support people to quit tobacco are not part of routine primary care in LICs. This study explored the challenges to implementing a behavioural support (BS) intervention to promote tobacco cessation within primary care in Nepal., Methods: The study used qualitative and quantitative methods within an action research approach in three primary health care centres (PHCCs) in two districts of Nepal. Before implementation, 21 patient interviews and two focus groups with health workers informed intervention design. Over a 6-month period, two researchers facilitated action research meetings with staff and observed implementation, recording the process and their reflections in diaries. Patients were followed up 3 months after BS to determine tobacco use (verified biochemically) and gain feedback on the intervention. A further five interviews with managers provided reflections on the process. The qualitative analysis used Normalisation Process Theory (NPT) to understand implementation., Results: Only 2 % of out-patient appointments identified the patient as a smoker. Qualitative findings highlight patients' unwillingness to admit their smoking status and limited motivation among health workers to offer the intervention. Patient-centred skills needed for BS were new to staff, who found them challenging particularly with low-literacy patients (skill set workability). Heath workers saw cessation advice and BS as an addition to their existing workload (relational integration). While there was strong policy buy-in, operationalising this through reporting and supervision was limited (contextual integration). Of the 44 patients receiving the intervention, 27 were successfully followed up after 3 months; 37 % of these had quit (verified biochemically)., Conclusions: Traditionally, primary health care in LICs has focused on acute care; with increasing recognition of the need for lifestyle change, health workers must develop new skills and relationships with patients. Appropriate and regular recording, reporting, supervision and clear leadership are needed if health workers are to take responsibility for smoking cessation. The consistent implementation of these health system activities is a requirement if cessation services are to be normalised within routine primary care.

Setting: Community health care providers (CHCPs) in 40 rural community clinics of Comilla district, Bangladesh, were trained using a newly developed case-management job aid based on the World Health Organization Integrated Management of Childhood Illness and a communication guide., Objectives: To assess 1) the change in knowledge of the CHCPs after training; 2) the absolute quality of care provided by the CHCPs (determined as the proportion of children aged <5 years [under-fives] correctly diagnosed, treated and referred); and 3) the consultation behaviour of the CHCPs., Design: Change in knowledge was assessed by tests pre-and post-training. The quality of care was determined by reassessments at the clinic exit by a medical officer, without a baseline comparison. Consultation behaviour was assessed through direct observation. The study was performed during 2014-2015., Results: The mean standard knowledge score of the CH-CPs increased from 19 to 25 (P < 0.001). Of 1490 under-fives examined, 91% were correctly diagnosed, 86% were correctly treated and 99.5% received a correct referral decision. The CHCPs performed well on most of the measures of good communication, although one third did not explain the diagnosis and treatment to patients., Conclusion: The training was effective in changing knowledge. The CHCPs applied the knowledge gained and provided good quality care. Following these results, the Bangladesh Ministry of Health and Family Welfare has scaled up the training nationwide. The lessons learnt should be useful for other countries.

Background: Schistosomiasis is a parasitic disease which affects almost 300 million people worldwide each year. It is highly endemic in Mozambique. Prevention and control of schistosomiasis relies mainly on mass drug administration (MDA), as well as adoption of basic sanitation practices. Individual and community perceptions of schistosomiasis are likely to have a significant effect on prevention and control efforts. In order to establish a baseline to evaluate a community engagement intervention with a focus on schistosomiasis, a survey to determine knowledge, attitudes and practices relating to the disease was conducted., Methodology/principal Findings: A representative cross-sectional household survey was carried out in four districts of Nampula province, Mozambique. Interviews were conducted in a total of 791 households, using a structured questionnaire. While awareness of schistosomiasis was high (91%), correct knowledge of how it is acquired (18%), transmitted (26%) and prevented (13%) was low among those who had heard of the disease. Misconceptions, such as the belief that schistosomiasis is transmitted through sexual contact (27%), were common. Only about a third of those who were aware of the disease stated that they practiced a protective behaviour and only a minority of those (39%) reported an effective behaviour. Despite several rounds of MDA for schistosomiasis in the recent past, only a small minority of households with children reported that at least one of them had received a drug to treat the disease (9%)., Conclusion/significance: Poor knowledge of the causes of schistosomiasis and how to prevent it, coupled with persisting misconceptions, continue to pose barriers to effective disease prevention and control. To achieve high levels of uptake of MDA and adoption of protective behaviours, it will be essential to engage individuals and communities, improving their understanding of the causes and symptoms of schistosomiasis, recommended prevention mechanisms and the rationale behind MDA.

We aimed to identify effective behaviour change techniques to increase modern contraceptive use in low and middle income countries (LMICs). Literature was identified in Global Health, Web of Science, MEDLINE, PsycINFO and Popline, as well as peer reviewed journals. Articles were included if they were written in English, had an outcome evaluation of contraceptive use, modern contraceptive use, contraceptive initiation/uptake, contraceptive adherence or continuation of contraception, were a systematic review or randomised controlled trial, and were conducted in a low or middle income country. We assessed the behaviour change techniques used in each intervention and included a new category of male partner involvement. We identified six studies meeting the inclusion criteria. The most effective interventions were those that involve male partner involvement in the decision to initiate contraceptive use. The findings also suggest that providing access to contraceptives in the community promotes their use. The interventions that had positive effects on contraceptive use used a combination of behaviour change techniques. Performance techniques were not used in any of the interventions. The use of social support techniques, which are meant to improve wider social acceptability, did not appear except in two of the interventions. Our findings suggest that when information and contraceptives are provided, contraceptive use improves. Recommendations include reporting of behaviour change studies to include more details of the intervention and techniques employed. There is also a need for further research to understand which techniques are especially effective.

Background: Worldwide, type 2 diabetes affects approximately 220 million people and is the cause of 1.1 million deaths each year, 80% of which occur in low and middle income countries (LMICs). Over the next 20 years, prevalence is expected to double worldwide and increase by 150% in LMICs. There is now a move towards improving care for diabetes. However no information on patients' needs, perceptions and experiences is available, hindering effective and appropriate changes in policy and practice. We developed a study with the objective of understanding patients' experiences of treatment for type 2 diabetes., Methods: During January 2011, we conducted in-depth interviews in five sites across two administrative districts of Bangladesh, purposefully chosen to represent different geographic regions and local demographics In total, we conducted 23 (14 male, 9 female) individual interviews across the 5 sites, to gain insight into patients' understanding of their diabetes and its management., Results: Patients' levels of knowledge and understanding about diabetes and its management is depended on where they received their initial diagnosis and care. Away from specialist centres, patients had poor understanding of the essential of diabetes and its management. No appropriate written or verbal information was available for a significant number of patients, compounded limited knowledge and understanding of diabetes by healthcare professionals. Patients felt that with improved provision of appropriate information they would be able to better understand their diabetes and improve their role in its management. Access to appropriate diagnosis and subsequent treatment was restricted by availability and costs of services., Conclusion: Effective, appropriate and essential healthcare services for diabetes in Bangladesh is extremely limited, a majority of patients receive suboptimal care. Site of diagnosis will impact significantly on the quality of information provided and the quality of subsequent treatments. Although appropriate services are available at some specialist centres, the inability of patients to pay for routine tests and check-ups prevents them from receiving timely diagnoses and appropriate continuity of care. The double burden of communicable diseases and diseases is now a well-recognised. Emphasis must be placed on developing appropriate and effective preventive strategies to address this burden.

Introduction: We explored the differential effect of cessation interventions (behavioral support sessions with [BSS+] and without [BSS] bupropion) between hookah and cigarette smokers., Methods: We reanalyzed the data from a major cluster-randomized controlled trial, ASSIST (Action to Stop Smoking In Suspected Tuberculosis), which consisted of 3 conditions: (a) behavioral support sessions (BSS), (b) behavioral support sessions plus 7 weeks of bupropion therapy (BSS+), and (c) controls receiving usual care. The trial originally recruited 1,955 adult smokers with suspected tuberculosis from 33 health centers in the Jhang and Sargodha districts of Pakistan between 2010 and 2011. The primary endpoint was continuous 6-month smoking abstinence, which was determined by carbon monoxide levels. Subgroup-specific relative risks (RRs) of smoking abstinence were computed and tested for differential intervention effect using log binomial regression (generalized linear model) between 3 subgroups (cigarette-only: 1,255; mixed: 485; and hookah-only: 215)., Results: The test result for homogeneity of intervention effects between the smoking forms was statistically significant (p-value for BSS+: .04 and for BSS: .02). Compared to the control, both interventions appeared to be effective among hookah smokers (RR = 2.5; 95% CI = 1.3-4.7 and RR = 2.2; 95% CI = 1.3-3.8, respectively) but less effective among cigarette smokers (RR = 6.6; 95% CI = 4.6-9.6 and RR = 5.8; 95% CI = 4.0-8.5), respectively., Conclusions: The differential intervention effects on hookah and cigarette smokers were seen (a) because the behavioral support intervention was designed primarily for cigarette smokers; (b) because of differences in demographic characteristics, behavioral, and sociocultural determinants; or (c) because of differences in nicotine dependency levels between the 2 groups.

Background: People with multi-drug resistant tuberculosis (MDR-TB) in low-income countries face many problems during treatment, and cure rates are low. The purpose of the study was (a) to identify and document the problems experienced by people receiving care for MDR-TB, and how they cope when support is not provided, to inform development of strategies; (b) to estimate the effectiveness of two resultant strategies, counselling alone, and joint counselling and financial support, of increasing DOTS-plus treatment success under routine programme conditions., Methods: A mixed-method study comprising a formative qualitative study, pilot intervention study and explanatory qualitative study to better understand barriers to completion of treatment for MDR-TB. Participants were all people starting MDR-TB treatment in seven DOTS-plus centres in the Kathmandu Valley, Nepal during January to December 2008. The primary outcome measure was cure, as internationally defined., Results: MDR-TB treatment caused extreme social, financial and employment hardship. Most patients had to move house and leave their job, and reported major stigmatisation. They were concerned about the long-term effects of their disease, and feared infecting others. In the resultant pilot intervention study, the two strategies appeared to improve treatment outcomes: cure rates for those receiving counselling, combined support and no support were 85%, 76% and 67% respectively. Compared with no support, the (adjusted) risk ratios of cure for those receiving counselling and receiving combined support were 1.2 (95% CI 1.0 to 1.6) and 1.2 (95% CI 0.9 to 1.6) respectively. The explanatory study demonstrated that patients valued both forms of support., Conclusions: MDR-TB patients are extremely vulnerable to stigma and extreme financial hardship. Provision of counselling and financial support may not only reduce their vulnerability, but also increase cure rates. National Tuberculosis Programmes should consider incorporating financial support and counselling into MDR-TB care: costs are low, and benefits high, especially since costs to society of incomplete treatment and potential for incurable TB are extremely high.

Objectives: In Bangladesh, second-hand smoke (SHS) is recognised as a principal source of indoor air pollution and a major public health problem. However, we know little about the extent to which people are aware of the risks of second-hand smoking, or restrict smoking indoors or in the presence of children. We report findings of a community survey exploring these questions., Design and Setting: A total of 722 households were surveyed in urban and rural settings, using a multistage cluster random sampling approach and a semistructured questionnaire. In addition, we used qualitative methods to further explore the determinants of smoking-related behaviours inside homes., Findings: 55% of households in our sample had at least one regular smoker. Smoking indoors was common. In 30% of households, smoking occurred in the presence of children, exposing nearly 40% of children to SHS. Overall, we found a lack of awareness about the harms associated with second-hand smoking., Conclusions: Our study highlights that a sizeable proportion of children and non-smokers are exposed to SHS at homes in Bangladesh, posing a significant and grave public health problem. In the absence of any impetus to legislate against smoking in private places, an educational approach is recommended to change smoking practices at home. Such a shift toward voluntary smoking restrictions at home would require behaviour change among smokers and support from non-smoking family members.

Background: Tobacco use is responsible for a large proportion of the total disease burden from tuberculosis. Pakistan is one of the 10 high-burden countries for both tuberculosis and tobacco use., Objective: To assess the effectiveness of a behavioral support intervention and bupropion in achieving 6-month continuous abstinence in adult smokers with suspected pulmonary tuberculosis., Design: Cluster randomized, controlled trial. (Current Controlled Trials: ISRCTN08829879), Setting: Health centers in the Jhang and Sargodha districts in Pakistan., Patients: 1955 adult smokers with suspected tuberculosis., Intervention: Health centers were randomly assigned to provide 2 brief behavioral support sessions (BSS), BSS plus 7 weeks of bupropion therapy (BSS+), or usual care., Measurements: The primary end point was continuous abstinence at 6 months after the quit date and was determined by carbon monoxide levels in patients. Secondary end points were point abstinence at 1 and 6 months., Results: Both treatments led to statistically significant relative risks (RRs) for abstinence compared with usual care (RR for BSS+, 8.2 [95% CI, 3.7 to 18.2]; RR for BSS, 7.4 [CI, 3.4 to 16.4]). Equivalence between the treatments could not be established. In the BSS+ group, 275 of 606 patients (45.4% [CI, 41.4% to 49.4%]) achieved continuous abstinence compared with 254 of 620 (41.0% [CI, 37.1% to 45.0%]) in the BSS group and 52 of 615 (8.5% [CI, 6.4% to 10.9%]) in the usual care group. There was substantial heterogeneity of program effects across clusters., Limitations: Imbalances in the urban and rural proportions and smoking habits among treatment groups, and inability to confirm adherence to bupropion treatment and validate longer-term abstinence or the effect of smoking cessation on tuberculosis outcomes., Conclusion: Behavioral support alone or in combination with bupropion is effective in promoting cessation in smokers with suspected tuberculosis., Primary Funding Source: International Development Research Centre.

Objectives: In Bangladesh, private healthcare is common and popular, regardless of income or area of residence, making the private sector an important player in health service provision. Although the private sector offers a good range of health services, tuberculosis (TB) care in the private sector is poor. We conducted research in Dhaka, between 2004 and 2008, to develop and evaluate a public-private partnership (PPP) model to involve private medical practitioners (PMPs) within the National TB Control Programme (NTP)'s activities. Since 2008, this PPP model has been scaled up in two other big cities, Chittagong and Sylhet. This paper reports the results of this development, evaluation and scale-up., Design: Mixed method, observational study design. We used NTP service statistics to compare the TB control outcomes between intervention and control areas. To capture detailed insights of PMPs and TB managers about the process and outcomes of the study, we conducted in-depth interviews, focus group discussions and workshops., Setting: Urban setting, piloted in four areas in Dhaka city; later scaled up in other areas of Dhaka and in two major cities., Findings: The partnership with PMPs yielded significantly increased case finding of sputum smear-positive TB cases. Between 2004 and 2010, 703 participating PMPs referred 3959 sputum smear-positive TB cases to the designated Directly Observed Treatment, Short-course (DOTS) centres, contributing about 36% of all TB cases in the project areas. There was a steady increase in case notification rates in the project areas following implementation of the partnership., Conclusions: The PPP model was highly effective in improving access and quality of TB care in urban settings.

Objectives: To implement and evaluate a public-private partnership model involving garment factories to reduce the tuberculosis (TB) burden in this workforce., Design: We used operational research to develop and evaluate a mechanism for effective and sustainable TB control in workplaces in three areas of Dhaka, Bangladesh. Strategies, protocols, guides and tools were developed with stakeholders. We assessed the impact of the project using quantitative and qualitative measures: changes in TB outcomes were calculated using standard indicators based on factory and DOTS centre records; changes in TB care-seeking behaviour were assessed using qualitative in-depth interviews with factory managers and medical personnel, and focus group discussions with factory workers, including TB patients., Findings: The project brought positive changes in knowledge, attitudes and practices of managers, workers and health care providers on TB care and control. During 2008-2010, a total of 3372 workers from a workforce of 69,000 were referred for sputum microscopy and 598 were diagnosed with smear-positive TB, 145 of whom received care at their workplace. The overall treatment success rate was 100%., Conclusion: It is feasible to engage factories in TB control activities in Bangladesh, and thereby increase case notifications and improve treatment outcomes.

A qualitative study was undertaken to attempt to understand reasons for the delayed diagnosis of tuberculosis (TB) amongst Ugandan women and to describe the nature of TB stigma and its effects in Uganda. Twelve women were interviewed. Participants were selected on the basis that they had smear-positive TB and had delayed consulting healthcare services for ≥30 days. Semi-structured interviews were conducted and analysed using thematic content analysis. The study showed that the main reason for delayed diagnosis amongst women interviewed was a lack of recognition of symptoms. This may be due to low levels of TB awareness in the community. The study also showed that TB is stigmatised in Uganda, mainly due to associations with HIV. Many participants believed that TB only exists with HIV and that TB causes HIV tests to appear negative even for HIV-infected people. Health education programmes would be helpful to improve the understanding of TB and to combat harmful beliefs about TB and HIV in the community.

Background: In 2004, the Ministry of Health issued the policy of decentralising microscopy services (MCs) to one third of all township hospitals in China. The study was conducted in Gansu Province, a poor western one in China. Ganzhou was one county in Gansu Province. Ganzhou County was identified as a unique case of further decentralisation of tuberculosis (TB) treatment services in township hospitals. The study evaluated the impact of the MC policy on providers and patients in Gansu Province. The second objective was to assess the unique case of Ganzhou County compared with other counties in the province., Methods: Both quantitative and qualitative methods were used. All 523 MCs in the province completed an institutional survey regarding their performance. Four counties were selected for in-depth investigation, where 169 TB suspects were randomly selected from the MC and county TB dispensary registers for questionnaire surveys. Informant interviews were conducted with 38 health staff at the township and county levels in the four counties., Results: Gansu established MCs in 39% of its township hospitals. From January 2006 to June 2007, 8% of MCs identified more than 10 TB sputum smear positive patients while 54% did not find any. MCs identified 1546 TB sputum smear positive patients, accounting for 9% of the total in the province. The throughputs of MCs in Ganzhou County were eight times of those in other counties. Interviews identified several barriers to implement the MC policy, such as inadequate health financing, low laboratory capacity, lack of human resources, poor treatment and management capacities, and lack of supervisions from county TB dispensaries., Conclusion: Microscopy centre throughputs were generally low in Gansu Province, and the contribution of MCs to TB case detection was insignificant taking account the number of MCs established. As a unique case of full decentralisation of TB service, Ganzhou County presented better results. However, standards and quality of TB care needed to be improved. The MC policy needs to be reviewed in light of evidence from this study.

Background: Many antiretroviral treatment (ART) adherence measurement methods have been employed by different studies, but no single method has been found to be appropriate for all settings. This study aimed to determine baseline levels of adherence using 2 measures of adherence., Methods: Levels of adherence in 967 patients continuing to receive ART in 4 health facilities were assessed over a 28-week period using a clinic-based pill count method and a patient self-report questionnaire. Factors associated with adherence were also determined., Results: Mean adherence (95% confidence interval) was 97.3% (96.8% to 97.9%) and 98.4% (97.9% to 98.8%) for the clinic-based pill count and patient self-report methods, respectively. Proportion of clients achieving optimal adherence (≥ 95%) was 89.9% by pill count and 94.2% by self-report. The 2 adherence measures were closely correlated with each other (r = 0.87, P = 0.000). Adherence increased with age (P = 0.014) with patients aged 40 years and below being less likely to achieve optimal adherence [odds ratio = 0.55; 95% confidence interval (0.34 to 0.89)]., Conclusions: There is a very high level of optimal adherence among patients still on treatment. The combined use of these 2 replicable and reliable methods of measuring adherence is vital to ART programs in resource-constrained settings.

Background: Genetically Modified (GM) crops have been championed as one possible method to improve food security and individual nutritional status in sub Saharan Africa. Understanding and acceptability of GM crop technology to farmers and consumers have not been assessed. We developed a qualitative research study involving farmers as both producers and consumers to gauge the understanding of GM crop technology, its acceptability, and identifying issues of concern., Methods: Nineteen individual interviews (10 male and 9 female) and five mixed gender focus group discussions with local farmers were conducted in 3 regions in Tanzania. Analysis took place concurrently with data collection. Following initial interviews, subsequent questions were adjusted based on emerging themes., Results: Understanding, awareness and knowledge of GM crop technology and terminology and its potential risks and benefits was very poor in all regions. Receptivity to the potential use of GM crops was, however, high. Respondents focused on the potential benefits of GM crops rather than any potential longer term health risks. A number of factors, most significantly field trial data, would influence farmers' decisions regarding the introduction of GM crop varieties into their farming practice. Understanding of the potential improved health provision possible by changes in agricultural practice and food-related decision making, and the health benefits of a diet containing essential vitamins, minerals and micronutrients is also poor in these communities., Conclusion: This study forms a basis from which further research work can be undertaken. It is important to continue to assess opinions and attitudes of farmers and consumers in sub Saharan Africa towards potential use of GM technologies whilst highlighting the importance of the relationship between agriculture, health and development. This will allow people in the region to make accurate, informed decisions about whether they believe use of GM biotechnology is an appropriate way in which to tackle issues of food security, provide improved health and drive development.

Background: Delays seeking care worsen the burden of tuberculosis and cost of care for patients, families and the public health system. This study investigates costs of tuberculosis diagnosis incurred by patients, escorts and the public health system in 10 districts of Ethiopia., Methods: New pulmonary tuberculosis patients > or = 15 years old were interviewed regarding their health care seeking behaviour at the time of diagnosis. Using a structured questionnaire patients were interviewed about the duration of delay at alternative care providers and the public health system prior to diagnosis. Costs incurred by patients, escorts and the public health system were quantified through patient interview and review of medical records., Results: Interviews were held with 537 (58%) smear positive patients and 387 (42%) smear negative pulmonary patients. Of these, 413 (45%) were female; 451 (49%) were rural residents; and the median age was 34 years. The mean (median) days elapsed for consultation at alternative care providers and public health facilities prior to tuberculosis diagnosis was 5 days (0 days) and 3 (3 days) respectively. The total median cost incurred from first consultation to diagnosis was $27 per patient (mean = $59). The median costs per patient incurred by patient, escort and the public health system were $16 (mean = $29), $3 (mean = $23) and $3 (mean = $7) respectively. The total cost per patient diagnosed was higher for women, rural residents; those who received government food for work support, patients with smear negative pulmonary tuberculosis and patients who were not screened for TB in at least one district diagnostic centers., Conclusions: The costs of tuberculosis diagnosis incurred by patients and escorts represent a significant portion of their monthly income. The costs arising from time lost in seeking care comprised a major portion of the total cost of diagnosis, and may worsen the economic position of patients and their families. Getting treatment from alternative sources and low index of suspicion public health providers were key problems contributing to increased cost of tuberculosis diagnosis. Thus, the institution of effective systems of referral, ensuring screening of suspects across the district public health system and the involvement of alternative care providers in district tuberculosis control can reduce delays and the financial burden to patients and escorts.

Objective: To establish which of the many possible linkages between tuberculosis (TB), direct observation of treatment (DOTS), and the social reality of migrant workers in Kathmandu are the most relevant to the health outcomes and economic and social well-being of these populations, and which are amenable to possible interventions and high-yield policy changes., Methods: Fourteen semi-structured in-depth interviews were conducted through an interpreter with male migrant TB patients aged 18-50 years recruited from three DOTS clinics in the Kathmandu valley in May 2005. The interviews were coded using constant comparison and analysed using a grounded theory method., Results: The economic burden of TB treatment is far greater than the financial reserve of migrants. Consequently remittances sent to families are reduced and migrants remain in debt long after treatment completion, tied to the treatment location paying off high interest loans. Forced to attend clinics far away from their home, and isolated by the stigma associated with TB, migrants are vulnerable without social support networks. Migrants find that daily clinic visits are incompatible with working schedules and important cultural festivals, which forces them into defaulting., Conclusion: The needs of migrant workers with TB living in Kathmandu are not being adequately met. Current service provision needs to be reviewed to build in greater flexibility and support for migrant men.

Background: Little is known about the quality of tuberculosis (TB) service delivery in public health facilities in Ethiopia and its association with patients' non-adherence to TB treatment. This study assessed the organization, management and processes of TB care delivery, and their effects on patients' adherence to TB treatment., Methods: The quality of TB care was investigated in 44 public health facilities from three perspectives: structure, processes of TB care delivery and patient treatment outcome. Quality of care was determined by adherence to national TB guidelines. On-site observations of TB service delivery and interviews with health providers were conducted to evaluate structural factors. Patients (n = 237) in the health facilities were interviewed prospectively at completion of their treatment to determine the quality of tuberculosis care delivered. Three measures of treatment adherence [treatment interruption (>or=2 weeks), availability of unused TB drugs and treatment default] were quantified from a review of patient treatment registers and an audit of unused TB drugs at patients' homes. Effects were identified of poor quality structures and processes of service delivery on these three measures of adherence., Results: TB care providers were untrained in 18 (44%) of 44 facilities and daily outpatient TB care was not given in 13 of 44 (25%). Among the 237 patients, 43% interrupted treatment for >or=15 days and 30% had at least 1 day's dose of TB drugs unused. Patients tended to interrupt and default from treatment when their care provider had been inadequately supervised by district TB control experts and was incapable of dealing with patients' minor illnesses. Unavailability of daily TB care in health facilities was associated with missing daily doses., Conclusion: Better training of TB care providers and district supervisory support could be important interventions to improve the quality of care delivery and patient adherence to treatment.

Objective: To understand barriers to tuberculosis (TB) care among migrant TB patients in Shanghai after the introduction of the TB-free treatment policy which has applied to migrants since 2003, and to provide policy recommendations to improve TB control in migrant populations in big cities., Methods: In-depth interviews were conducted with 34 migrant patients who registered on the Shanghai TB programme as new bacteria positive pulmonary TB cases. Patients were purposively selected across six districts of Shanghai to give a balance of gender and TB treatment phase., Results: Financial constraints were reported as the biggest barriers to TB service among migrant patients. Many migrant patients experienced high medical costs both before and after their TB diagnosis. The government free treatment policy only covered a small fraction of patients' total costs. However, respondents tended to stay in Shanghai for treatment because their families were in Shanghai, they were more confident with the quality of medical care there or they felt they could not earn cash at home. Migrant patients had a limited knowledge of TB and the free TB treatment policy, and reported being laid off from work or avoided after having TB., Conclusions: Health system problems caused the biggest barrier to migrant patients' access to TB care. The free treatment policy alone has little, if any, effect in reducing migrant patients' financial stress: it is also essential to provide social welfare, including living subsidies, for poor migrant TB patients.

Current therapy with immediate-release hydrocortisone is the most commonly used regimen for replacement in patients with primary and secondary adrenal insufficiency. However, conventional hydrocortisone cannot provide the physiological rhythm of cortisol release. Physicians have used fixed twice- or thrice-daily doses, but these regimens inevitably result in temporary over- or under-replacement. Patients with adrenal insufficiency, although on treatment, have a poor quality of life and an increased mortality. Optimization of current treatment has been attempted with thrice-daily, weight-related dosing, but this still fails to simulate the normal diurnal rhythm of cortisol. Recent research has investigated circadian hydrocortisone therapy imitating the physiological cortisol rhythm. Proof-of-concept studies using hydrocortisone infusions predict improvements in biochemical control and quality of life. Now delayed and sustained release oral formulations of hydrocortisone are being developed, and these offer a more practical and effective solution for patients with adrenal insufficiency and congenital adrenal hyperplasia.

Background: Delays seeking care increase transmission of pulmonary tuberculosis and hence the burden of tuberculosis, which remains high in developing countries. This study investigates patterns of health seeking behavior and determines risk factors for delayed patient consultation at public health facilities in 10 districts of Ethiopia., Methods: New pulmonary TB patients >or= 15 years old were recruited at 18 diagnostic centres. Patients were asked about their health care seeking behaviour and the time from onset of symptoms to first consultation at a public health facility. First consultation at a public health facility 30 days or longer after onset of symptoms was regarded as prolonged patient delay., Results: Interviews were held with 924 pulmonary patients. Of these, 537 (58%) were smear positive and 387 (42%) were smear negative; 413 (45%) were female; 451 (49%) were rural residents; and the median age was 34 years. Prior to their first consultation at a public health facility, patients received treatment from a variety of informal sources: the Orthodox Church, where they were treated with holy water (24%); private practitioners (13%); rural drug vendors (7%); and traditional healers (3%). The overall median patient delay was 30 days (mean = 60 days). Fifty three percent [95% Confidence Intervals (CI) (50%, 56%)] of patients had delayed their first consultation for >or= 30 days. Patient delay for women was 54%; 95% CI (54%, 58%) and men 51%; 95% CI (47%, 55%). The delay was higher for patients who used informal treatment (median 31 days) than those who did not (15 days). Prolonged patient delay (>or= 30 days) was significantly associated with both patient-related and treatment-related factors. Significant patient-related factors were smear positive pulmonary disease [Adjusted Odds Ratio (AOR) 1.4; 95% CI (1.1 to 1.9)], rural residence [AOR 1.4; 95% CI (1.1 to 1.9)], illiteracy [AOR 1.7; 95% CI (1.2 to 2.4)], and lack of awareness/misperceptions of causes of pulmonary TB. Significant informal treatment-related factors were prior treatment with holy water [AOR 3.5; 95% CI (2.4 to 5)], treatment by private practitioners [AOR 1.7; 95% CI (1.1 to 2.6)] and treatment by drug vendors [AOR 1.9; 95% CI (1.1 to 3.5)]., Conclusion: Nearly half of pulmonary tuberculosis patients delayed seeking health care at a public health facility while getting treatment from informal sources. The involvement of religious institutions and private practitioners in early referral of patients with pulmonary symptoms and creating public awareness about tuberculosis could help reduce delays in starting modern treatment.

Background: Two TB control strategies appropriate for South Asia (a community-based DOTS [CBD] strategy and a family-based DOTS [FBD] strategy) have been shown to be effective in Nepal in meeting the global target for the proportion of registered patients successfully treated. Here we estimate the costs and cost-effectiveness of the two strategies. This information is essential to allow meaningful comparisons between these and other strategies and will contribute to the small but growing body of knowledge on the costs and cost-effectiveness of different approaches to TB control., Methods: In 2001-2, costs relating to TB diagnosis and care were collected for each strategy. Structured and semi-structured questionnaires were used to collect costs from health facility records and a sample of 10 patients in each of 10 districts, 3 using CBD and 2 using FBD. The data collected included costs to the health care system and social costs (including opportunity costs) incurred by patients and their supervisors. The cost-effectiveness of each strategy was estimated., Results: Total recurrent costs per patient using the CBD and FBD strategies were US$76.2 and US$84.1 respectively. The social costs incurred by patients and their supervisors represent more than a third of total recurrent costs under each strategy (37% and 35% respectively). The CBD strategy was more cost-effective than the FBD strategy: recurrent costs per successful treatment were US$91.8 and US$102.2 respectively., Discussion: Although the CBD strategy was more cost-effective than the FBD strategy in the study context, the estimates of cost-effectiveness were sensitive to relatively small changes in underlying costs and treatment outcomes. Even using these relatively patient-friendly approaches to DOTS, social costs can represent a significant financial burden for TB patients.

Objectives: To assess the effectiveness of clinical audit in improving the quality of diagnostic care provided to patients suspected of tuberculosis; and to understand the contextual factors which impede or facilitate its success., Methods: Twenty-six health centres in Cuba, Peru and Bolivia were recruited. Clinical audit was introduced to improve the diagnostic care for patients attending with suspected TB. Standards were based on the WHO and TB programme guidelines relating to the appropriate use of microscopy, culture and radiological investigations. At least two audit cycles were completed over 2 years. Improvement was determined by comparing the performance between two six-month periods pre- and post-intervention. Qualitative methods were used to ascertain facilitating and limiting contextual factors influencing change among healthcare professionals' clinical behaviour after the introduction of clinical audit., Results: We found a significant improvement in 11 of 13 criteria in Cuba, in 2 of 6 criteria in Bolivia and in 2 of 5 criteria in Peru. Twelve out of 24 of the audit criteria in all three countries reached the agreed standards. Barriers to quality improvement included conflicting objectives for clinicians and TB programmes, poor coordination within the health system and patients' attitudes towards illness., Conclusions: Clinical audit may drive improvements in the quality of clinical care in resource-poor settings. It is likely to be more effective if integrated within and supported by the local TB programmes. We recommend developing and evaluating an integrated model of quality improvement including clinical audit.

Background: Tuberculosis (TB) is a major cause of death. The condition is highly stigmatised, with considerable discrimination towards sufferers. Although there have been several studies assessing the extent of such discrimination, there is little published research explicitly investigating the causes of the stigma and discrimination associated with TB. The objectives of our research were therefore to take the first steps towards determining the causes of discrimination associated with TB., Methods: Data collection was performed in Kathmandu, Nepal. Thirty four in-depth interviews were performed with TB patients, family members of patients, and members of the community., Results: Causes of self-discrimination identified included fear of transmitting TB, and avoiding gossip and potential discrimination. Causes of discrimination by members of the general public included: fear of a perceived risk of infection; perceived links between TB and other causes of discrimination, particularly poverty and low caste; perceived links between TB and disreputable behaviour; and perceptions that TB was a divine punishment. Furthermore, some patients felt they were discriminated against by health workers, Conclusion: A comprehensive package of interventions, tailored to the local context, will be needed to address the multiple causes of discrimination identified: basic population-wide health education is unlikely to be effective.

Setting: Sixteen primary care health centres in Peru and Bolivia., Objectives: To assess the utilisation of microscopy services in Peru and Bolivia and determine if clinical audit, a quality improvement tool, improves the utilisation of these services., Design: We estimated the percentage of patients with suspected tuberculosis (TB) in whom sputum microscopy was effectively utilised in Peru and Bolivia over two 6-month periods before and after a clinical audit intervention that included standards setting, measuring clinical performance and feedback., Results: Before the intervention, only 31% (95%CI 27-35) of TB suspects were assessed with sputum microscopy in Peru. In Bolivia, 30% (95%CI 25-35) underwent at least two sputum microscopy examinations. After clinical audit, the availability of sputum microscopy results improved by respectively 7% (95%CI 1-12, P < 0.05) and 23% (95%CI 15-30, P < 0.05) over 2 years in Peru and Bolivia., Conclusions: Despite World Health Organization recommendations that all TB suspects should undergo sputum microscopy before treatment, results are available for further assessment for only one third. This is a potentially serious obstacle to TB case detection. Clinical audit can bring some improvement. We recommend regular monitoring of effective utilisation of microscopy services and investigations to ascertain organisational and structural issues in their uptake and use.