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Background: WHO recommends that electronic medication monitors, a form of digital adherence technology, be used as a complement to directly observed treatment (DOT) for tuberculosis, as DOT is inconvenient and costly. However, existing evidence about the effectiveness of these monitors is inconclusive. Therefore, we evaluated the effectiveness of a comprehensive package based on electronic medication monitors among patients with tuberculosis in Tibet Autonomous Region (hereafter Tibet), China., Methods: This multicentre, randomised controlled trial recruited patients from six counties in Shigatse, Tibet. Eligible participants had drug-susceptible tuberculosis and were aged 15 years or older when starting standard tuberculosis treatment. Tuberculosis doctors recruited patients from the public tuberculosis dispensary in each county and the study statistician randomly assigned them to the intervention or control group based on the predetermined randomised allocation sequence. Intervention patients received an electronic medication monitor box. The box included audio medication-adherence reminders and recorded box-opening data, which were transmitted to a cloud-based server and were accessible to health-care providers to allow remote adherence monitoring. A linked smartphone app enabled text, audio, and video communication between patients and health-care providers. Patients were also provided with a free data plan. Patients selected a treatment supporter (often a family member) who was trained to support patients with using the electronic medication monitor and app. Patients in the control group received usual care plus a deactivated electronic medication monitor, which only recorded and transmitted box-opening data that was not made available to health-care providers. The control group also had no access to the app or trained treatment supporters. The primary outcome was a binary indicator of poor monthly adherence, defined as missing 20% or more of planned doses in the treatment month, measured using electronic medication monitor opening data, and verified by counting used medication blister packages during consultations. We recorded other secondary treatment outcomes based on national tuberculosis reporting data. We analysed the primary outcome based on the intention-to-treat population. This trial is registered at ISRCTN, 52132803., Findings: Between Nov 17, 2018, and April 5, 2021, 278 patients were enrolled into the study. 143 patients were randomly assigned to the intervention group and 135 patients to the control group. Follow-up ended when the final patient completed treatment on Oct 4, 2021. In the intervention group, 87 (10%) of the 854 treatment months showed poor adherence compared with 290 (37%) of the 795 months in the control group. The corresponding adjusted risk difference for the intervention versus control was -29·2 percentage points (95% CI -35·3 to -22·2; p<0·0001). Five of the six secondary treatment outcomes also showed clear improvements, including treatment success, which was found for 133 (94%) of the 142 individuals in the intervention arm and 98 (73%) of the 134 individuals in the control arm, with an adjusted risk difference of 21 percentage points (95% CI 12·4-29·4); p<0·0001., Interpretation: The interventions were effective at improving tuberculosis treatment adherence and outcomes, and the trial suggests that a comprehensive package involving electronic medication monitors might positively affect tuberculosis programmes in high-burden and low-resource settings., Funding: TB REACH., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

BACKGROUND Multidrug-resistant TB (MDR-TB) treatment takes 18-24 months and is complex, costly and isolating. We provide trial evidence on the WHO Pakistan recommendation for community-based care rather than hospital-based care. METHODS Two-arm, parallel-group, superiority trial was conducted in three programmatic management of drug-resistant TB hospitals in Punjab and Sindh Provinces, Pakistan. We enrolled 425 patients with MDR-TB aged >15 years through block randomisation in community-based care (1-week hospitalisation) or hospital-based care (2 months hospitalisation). Primary outcome was treatment success. RESULTS Among 425 patients with MDR-TB, 217 were allocated to community-based care and 208 to hospital-based care. Baseline characteristics were similar between the community and hospitalised arms, as well as in selected sites. Treatment success was 74.2% (161/217) under community-based care and 67.8% (141/208) under hospital-based care, giving a covariate-adjusted risk difference (community vs. hospital model) of 0.06 (95% CI -0.02 to 0.15; P = 0.144). CONCLUSIONS We found no clear evidence that community-based care was more or less effective than hospital-based care model. Given the other substantial advantages of community-based care over hospital based (e.g., more patient-friendly and accessible, with lower treatment costs), this supports the adoption of the community-based care model, as recommended by the WHO.

Background: The in-service training of frontline health workers (FHWs) in primary health care facilities plays an important role in improving the standard of health care delivery. However, it is often expensive and requires FHWs to leave their posts in rural areas to attend courses in urban centers. This study reports the implementation of a digital health tool for providing video training (VTR) on maternal, newborn, and child health (MNCH) care to provide in-service training at scale without interrupting health services. The VTR intervention was supported by satellite communications technology and existing 3G mobile networks., Objective: This study aims to determine the feasibility and acceptability of these digital health tools and their potential effectiveness in improving clinical knowledge, attitudes, and practices related to MNCH care., Methods: A mixed methods design, including an uncontrolled pre- and postquantitative evaluation, was adopted. From October 2017 to May 2018, a VTR mobile intervention was delivered to FHWs in 3 states of Nigeria. We examined changes in workers' knowledge and confidence in delivering MNCH services through a pre- and posttest survey. Stakeholders' experiences with the intervention were explored through semistructured interviews that drew on the technology acceptance model to frame contextual factors that shaped the intervention's acceptability and usability in the work environment., Results: In total, 328 FHWs completed both pre- and posttests. FHWs achieved a mean pretest score of 51% (95% CI 48%-54%) and mean posttest score of 69% (95% CI 66%-72%), reflecting, after adjusting for key covariates, a mean increase between the pre- and posttest of 17 percentage points (95% CI 15-19; P<.001). Variation was identified in pre- and posttest scores by the sex and location of participants alongside topic-specific areas where scores were lowest. Stakeholder interviews suggested a wide acceptance of VTR Mobile (delivered via digital technology) as an important tool for enhancing the quality of training, reinforcing knowledge, and improving health outcomes., Conclusions: This study found that VTR supported through a digital technology approach is a feasible and acceptable approach for supporting improvements in clinical knowledge, attitudes, and reported practices in MNCH. The determinants of technology acceptance included ease of use, perceived usefulness, access to technology and training contents, and the cost-effectiveness of VTR, whereas barriers to the adoption of VTR were poor electricity supply, poor internet connection, and FHWs' workload. The evaluation also identified the mechanisms of the impact of delivering VTR Mobile at scale on the micro (individual), meso (organizational), and macro (policy) levels of the health system. Future research is required to explore the translation of this digital health approach for the VTR of FHWs and its impact across low-resource settings to ameliorate the financial and time costs of training and support high-quality MNCH care delivery., Trial Registration: ISRCTN Registry 32105372; https://www.isrctn.com/ISRCTN32105372., (©Joseph Paul Hicks, Matthew John Allsop, Godwin O Akaba, Ramsey M Yalma, Osasuyi Dirisu, Babasola Okusanya, Jamilu Tukur, Kehinde Okunade, David Akeju, Adegbenga Ajepe, Okey Okuzu, Tolib Mirzoev, Bassey Ebenso. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 16.09.2021.)

Background: Primary prevention of cardiovascular disease (CVD) requires adequate control of hypertension and diabetes. We designed and implemented pharmaceutical and healthy lifestyle interventions for patients with diabetes and/or hypertension in rural primary care, and assessed their effectiveness at reducing severe CVD events., Methods and Findings: We used a pragmatic, parallel group, 2-arm, controlled, superiority, cluster trial design. We randomised 67 township hospitals in Zhejiang Province, China, to intervention (34) or control (33). A total of 31,326 participants were recruited, with 15,380 in the intervention arm and 15,946 in the control arm. Participants had no known CVD and were either patients with hypertension and a 10-year CVD risk of 20% or higher, or patients with type 2 diabetes regardless of their CVD risk. The intervention included prescription of a standardised package of medicines, individual advice on lifestyle change, and adherence support. Control was usual hypertension and diabetes care. In both arms, as usual in China, most outpatient drug costs were out of pocket. The primary outcome was severe CVD events, including coronary heart disease and stroke, during 36 months of follow-up, as recorded by the CVD surveillance system. The study was implemented between December 2013 and May 2017. A total of 13,385 (87%) and 14,745 (92%) participated in the intervention and control arms, respectively. Their mean age was 64 years, 51% were women, and 90% were farmers. Of all participants, 64% were diagnosed with hypertension with or without diabetes, and 36% were diagnosed with diabetes only. All township hospitals and participants completed the 36-month follow-up. At 36 months, there were 762 and 874 severe CVD events in the intervention and control arms, respectively, yielding a non-significant effect on CVD incidence rate (1.92 and 2.01 per 100 person-years, respectively; crude incidence rate ratio = 0.90 [95% CI: 0.74, 1.08; P = 0.259]). We observed significant, but small, differences in the change from baseline to follow-up for systolic blood pressure (-1.44 mm Hg [95% CI: -2.26, -0.62; P < 0.001]) and diastolic blood pressure (-1.29 mm Hg [95% CI: -1.77, -0.80; P < 0.001]) in the intervention arm compared to the control arm. Self-reported adherence to recommended medicines was significantly higher in the intervention arm compared with the control arm at 36 months. No safety concerns were identified. Main study limitations include all participants being informed about their high CVD risk at baseline, non-blinding of participants, and the relatively short follow-up period available for judging potential changes in rates of CVD events., Conclusions: The comprehensive package of pharmaceutical and healthy lifestyle interventions did not reduce severe CVD events over 36 months. Improving health system factors such as universal coverage for the cost of essential medicines is required for successful risk-based CVD prevention programmes., Trial Registration: ISRCTN registry ISRCTN58988083., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Health systems responsiveness is a key objective of any health system, yet it is the least studied of all objectives particularly in low-income and middle-income countries. Research on health systems responsiveness highlights its multiple elements, for example, dignity and confidentiality. Little is known, however, about underlying theories of health systems responsiveness, and the mechanisms through which responsiveness works. This realist synthesis contributes to bridging these two knowledge gaps., Methods and Analysis: In this realist synthesis, we will use a four-step process, comprising: mapping of theoretical bases, formulation of programme theories, theory refinement and testing of programme theories using literature and empirical data from Ghana and Vietnam. We will include theoretical and conceptual pieces, reviews, empirical studies and grey literature, alongside the primary data. We will explore responsiveness as entailing external and internal interactions within health systems. The search strategy will be purposive and iterative, with continuous screening and refinement of theories. Data extraction will be combined with quality appraisal, using appropriate tools. Each fragment of evidence will be appraised as it is being extracted, for its relevance to the emerging programme theories and methodological rigour. The extracted data pertaining to contexts, mechanisms and outcomes will be synthesised to identify patterns and contradictions. Results will be reported using narrative explanations, following established guidance on realist syntheses., Ethics and Dissemination: Ethics approvals for the wider RESPONSE (Improving health systems responsiveness to neglected health needs of vulnerable groups in Ghana and Vietnam) study, of which this review is one part, were obtained from the ethics committees of the following institutions: London School of Hygiene and Tropical Medicine (ref: 22981), University of Leeds, School of Medicine (ref: MREC19-051), Ghana Health Service (ref: GHS-ERC 012/03/20) and Hanoi University of Public Health (ref: 020-149/DD-YTCC).We will disseminate results through academic papers, conference presentations and stakeholder workshops in Ghana and Vietnam., Prospero Registration Number: CRD42020200353. Full record: https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42020200353., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: Antibiotic resistance is a global threat to human health, and inappropriate use of antibiotics in humans and animals is widely considered to be a key driver of antibiotic resistant infections. Antibiotic use in humans and animals is growing rapidly in low- and, particularly, middle-income countries. However, there is little detailed understanding about practices related to the use of antibiotics in humans and animals within community settings in such countries. Here we aimed to understand the antibiotic practices of rural households across Cumilla district, Bangladesh, in relation to household members and their domestic animals., Methods: In 2018 we conducted a cross-sectional survey using representative cluster sampling methods. We collected self-reported information from 682 female and 620 male household heads, with women also asked about their children's antibiotic practices., Results: Only 48% (95% CI: 40, 56%) of women and men had heard of antibiotics, and among those women and men who were aware of antibiotics and the children of those women 70% (95% CI: 64, 76%) reported having previously taken antibiotics, while among these individuals who reported previously taking antibiotics 21% (95% CI: 18, 25%) said they had done so most recently within the last month. Risky/inappropriate antibiotic practices in humans and animals were often reported. For example, among women and men who were aware of antibiotics and the children of those women 52% (95% CI: 40, 63%) reported previously taking antibiotics for a "cough/cold", despite antibiotics being typically inappropriate for use against viral upper respiratory tract infections. Among poultry-owning respondents who were aware of antibiotics 11% (95% CI: 8, 15%) reported previously giving healthy poultry antibiotics, mainly for growth/prophylaxis, while among cattle-owning respondents who were aware of antibiotics and reported previously giving their cattle feed 20% (95% CI: 9, 37%) said the feed had contained antibiotics at least sometimes., Conclusions: Our results highlight the need for context-adapted interventions at both the community level and the health systems level to reduce inappropriate antibiotic use among humans and domestic animals in rural Bangladesh. Successfully reducing inappropriate use of antibiotics among humans and animals is a required and critical step in tackling antimicrobial resistance.

The methods used in low- and middle-income countries' (LMICs) household surveys have not changed in four decades; however, LMIC societies have changed substantially and now face unprecedented rates of urbanization and urbanization of poverty. This mismatch may result in unintentional exclusion of vulnerable and mobile urban populations. We compare three survey method innovations with standard survey methods in Kathmandu, Dhaka, and Hanoi and summarize feasibility of our innovative methods in terms of time, cost, skill requirements, and experiences. We used descriptive statistics and regression techniques to compare respondent characteristics in samples drawn with innovative versus standard survey designs and household definitions, adjusting for sample probability weights and clustering. Feasibility of innovative methods was evaluated using a thematic framework analysis of focus group discussions with survey field staff, and via survey planner budgets. We found that a common household definition excluded single adults (46.9%) and migrant-headed households (6.7%), as well as non-married (8.5%), unemployed (10.5%), disabled (9.3%), and studying adults (14.3%). Further, standard two-stage sampling resulted in fewer single adult and non-family households than an innovative area-microcensus design; however, two-stage sampling resulted in more tent and shack dwellers. Our survey innovations provided good value for money, and field staff experiences were neutral or positive. Staff recommended streamlining field tools and pairing technical and survey content experts during fieldwork. This evidence of exclusion of vulnerable and mobile urban populations in LMIC household surveys is deeply concerning and underscores the need to modernize survey methods and practices.

Background: Socio-economic growth in many low and middle-income countries has resulted in more available, though not equitably accessible, healthcare. Such growth has also increased demands from citizens for their health systems to be more responsive to their needs. This paper shares a protocol for the RESPONSE study which aims to understand, co-produce, implement and evaluate context-sensitive interventions to improve health systems responsiveness to health needs of vulnerable groups in Ghana and Vietnam., Methods: We will use a realist mixed-methods theory-driven case study design, combining quantitative (household survey, secondary analysis of facility data) and qualitative (in-depth interviews, focus groups, observations and document and literature review) methods. Data will be analysed retroductively. The study will comprise three Phases. In Phase 1, we will understand actors' expectations of responsive health systems, identify key priorities for interventions, and using evidence from a realist synthesis we will develop an initial theory and generate a baseline data. In Phase 2, we will co-produce jointly with key actors, the context-sensitive interventions to improve health systems responsiveness. The interventions will seek to improve internal (i.e. intra-system) and external (i.e. people-systems) interactions through participatory workshops. In Phase 3, we will implement and evaluate the interventions by testing and refining our initial theory through comparing the intended design to the interventions' actual performance., Discussion: The study's key outcomes will be: (1) improved health systems responsiveness, contributing to improved health services and ultimately health outcomes in Ghana and Vietnam and (2) an empirically-grounded and theoretically-informed model of complex contexts-mechanisms-outcomes relations, together with transferable best practices for scalability and generalisability. Decision-makers across different levels will be engaged throughout. Capacity strengthening will be underpinned by in-depth understanding of capacity needs and assets of each partner team, and will aim to strengthen individual, organisational and system level capacities., Competing Interests: The authors have declared that no competing interests exist.

Background: Centre-based child-care has potential to provide multiple health and development benefits to children, families and societies. With rapid urbanisation, increasing numbers of low-income women work with reduced support from extended family, leaving a child-care vacuum in many low- and middle-income countries. We aimed to understand perceptions of, and demand for, centre-based child-care in Dhaka, Bangladesh among poor, urban households, and test the feasibility of delivering sustainable centre-based child-care., Methods: We used sequential mixed methods including a household survey (n = 222) and qualitative interviews with care-givers (n = 16), community leaders (n = 5) and policy-makers (n = 5). We co-produced and piloted a centre-based child-care model over ten-months, documenting implementation. A co-design focus group with mothers, parents' meetings, and qualitative interviews with child-care centre users (n = 5), non-users (n = 3), ex-users (n = 3) and staff (2) were used to refine the model and identify implementation issues., Results: We found 24% (95% CI: 16,37%) of care-givers reported turning-down paid work due to lack of child-care and 84% (95% CI:74, 91%) reported wishing to use centre-based child-care and were willing to pay up to 283 Takka (~$3.30) per month. Adjusted odds of reported need for child-care among slum households were 3.8 times those of non-slum households (95% CI: 1.4, 10). Implementation highlighted that poor households needed free child-care with food provided, presenting feasibility challenges. Meta-inference across quantitative and qualitative findings identified the impact of the urban environment on child-care through long working hours, low social capital and fears for child safety. These influences interacted with religious and social norms resulting in caution in using centre-based child-care despite evident need., Conclusion: Sustainable provision of centre-based care that focuses on early childhood development requires subsidy and careful design sensitive to the working lives of poor families, particularly women and must respond to the dynamics of the urban environment and community values. We recommend increased research and policy focus on the evaluation and scale-up of quality centre-based child-care, emphasising early-childhood development, to support low-income working families in urban areas.

Background: The Subsidy Reinvestment and Empowerment Programme (SURE-P), Maternal and Child Health (MCH) was introduced by the Nigerian government to increase the use of skilled maternal health services and reduce maternal mortality. The programme, funded out of a reduction in the fuel subsidy, was implemented between October 2012 and April 2015 and incorporated a conditional cash transfer to women to encourage use of facility based maternal services. We seek to assess the incremental cost effectiveness and long term impact of the conditional cash transfer element of the programme. Methods: An impact analysis and incremental cost-effectiveness analysis of conditional cash transfers (CCTs) is undertaken taking a health service perspective toward costs of the intervention. The study was undertaken in Anambra state, comparing areas that received only the investment in health services with areas that implemented the conditional cash transfer programme. An interrupted time series analysis of the programme outputs was undertaken. These were combined with a programme costing to determine the incremental cost per output. Findings: Maternal services provided to patients in conditional cash transfer areas accelerated rapidly from the middle of 2014 until after the programme in late 2015. The costs of providing services in each Primary Health Center facility was US $52,128 in the areas that only invested in health services compared to US $90,702 in facilities that also provided cash transfers. Much of the additional cost was in managing cash transfers. The incremental cost in the cash transfer areas was $572 for delivery care and $11 for antenatal care. If the programme was to be integrated as a regular service in the public health system, the cost of a delivery is estimated to fall to $389 and to $188 if 2015 levels of activity are assumed. Conclusion: Although the cost of CCTs as originally constituted as a vertical programme are relatively high compared to other similar programmes, these would fall substantially if integrated into the main health system. There is also evidence of sustained impact beyond the end of the funding suggesting that short term programmes can lead to a long-term change in patterns of health seeking behavior., (Copyright © 2020 Onwujekwe, Ensor, Ogbozor, Okeke, Ezenwaka, Hicks, Etiaba, Uzochukwu, Ebenso and Mirzoev.)

Introduction: Well-trained, adequately skilled and motivated primary healthcare (PHC) workers are essential for attaining universal health coverage (UHC). While there is abundant literature on the drivers of workforce motivation, published knowledge on the mechanisms of motivation within different contexts is limited, particularly in resource-limited countries. This paper contributes to health workforce literature by reporting on how motivation works among PHC workers in a maternal and child health (MCH) programme in Nigeria., Methods: We adopted a realist evaluation design combining document review with 56 in-depth interviews of PHC workers, facility managers and policy-makers to assess the impact of the MCH programme in Anambra State, Nigeria. A realist process of theory development, testing and consolidation was used to understand how and under what circumstances the MCH programme impacted on workers' motivation and which mechanisms explain how motivation works. We drew on Herzberg's two-factor and Adam's equity theories to unpack how context shapes worker motivation., Results: A complex and dynamic interaction between the MCH programme and organisational and wider contexts triggered five mechanisms which explain PHC worker motivation: (1) feeling supported, (2) feeling comfortable with work environment, (3) feeling valued, (4) morale and confidence to perform tasks and (5) companionship. Some mechanisms were mutually reinforcing while others operated in parallel. Other conditions that enabled worker motivation were organisational values of fairness, recognition of workers' contributions and culture of task-sharing and teamwork., Conclusions: Policy designs and management strategies for improving workforce performance, particularly in resource-constrained settings should create working environments that foster feelings of being valued and supported while enabling workers to apply their knowledge and skills to improve healthcare delivery and promote UHC. Future research can test the explanatory framework generated by this study and explore differences in motivational mechanisms among different cadres of PHC workers to inform cadre-related motivational interventions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Background: Understanding of the relationship between multi-drug resistant tuberculosis and mental health is limited. With growing prevalence of multi-drug resistant tuberculosis, addressing mental ill-health has potential to improve treatment outcomes and well-being. In several low and middle-income contexts hospitalisation during treatment is common. Understanding of the impact on mental ill-health are required to inform interventions for patients with multi-drug resistant tuberculosis. Our aim was to identify the prevalence of comorbid depression among in-patients being treated for multi-drug resistant tuberculosis and to explore their experiences of comorbid disease and the care they received in a large specialist chest hospital in Dhaka, Bangladesh., Methods: We conducted a quantitative cross-sectional survey among 150 multi-drug resistant tuberculosis in-patients (new cases = 34%, previously treated = 66%) in 2018. A psychiatrist assessed depression was assessed with the Structured Clinical Interview for Depression (SCID DSM-IV). We used multi-level modelling to identify associations with depression. Experience Bangladeshi researchers conducted qualitative interviews with 8 patients, 4 carers, 4 health professionals and reflective notes recorded. Qualitative data was analysed thematically., Results: We found 33.8% (95% CI 26.7%; 41.7%) of patients were depressed. While more women were depressed 39.3% (95% CI 27.6%; 52.4%) than men 30.4% (95% CI 22%; 40.5%) this was not significant. After controlling for key variables only having one or more co-morbidity (adjusted odds ratio [AOR] = 2.88 [95% CI 1.13; 7.33]) and being a new rather than previously treated case (AOR = 2.33 [95% CI 1.06; 5.14]) were associated (positively) with depression. Qualitative data highlighted the isolation and despair felt by patients who described a service predominantly focused on providing medicines. Individual, familial, societal and health-care factors influenced resilience, nuanced by gender, socio-economic status and home location., Conclusions: Patients with multi-drug resistant tuberculosis are at high risk of depression, particularly those with co- and multi-morbidities. Screening for depression and psycho-social support should be integrated within routine TB services and provided throughout treatment.

Background: Inappropriate prescribing of antibiotics for acute respiratory infections at the primary care level represents the major source of antibiotic misuse in healthcare, and is a major driver for antimicrobial resistance worldwide. In this study we will develop, pilot and evaluate the effectiveness of a comprehensive antibiotic stewardship programme in China's primary care hospitals to reduce inappropriate prescribing of antibiotics for acute respiratory infections among all ages., Methods: We will use a parallel-group, cluster-randomised, controlled, superiority trial with blinded outcome evaluation but unblinded treatment (providers and patients). We will randomise 34 primary care hospitals from two counties within Guangdong province into the intervention and control arm (1:1 overall ratio) stratified by county (8:9 within-county ratio). In the control arm, antibiotic prescribing and management will continue through usual care. In the intervention arm, we will implement an antibiotic stewardship programme targeting family physicians and patients/caregivers. The family physician components include: (1) training using new operational guidelines, (2) improved management and peer-review of antibiotic prescribing, (3) improved electronic medical records and smart phone app facilitation. The patient/caregiver component involves patient education via family physicians, leaflets and videos. The primary outcome is the proportion of prescriptions for acute respiratory infections (excluding pneumonia) that contain any antibiotic(s). Secondary outcomes will address how frequently specific classes of antibiotics are prescribed, how frequently key non-antibiotic alternatives are prescribed and the costs of consultations. We will conduct a qualitative process evaluation to explore operational questions regarding acceptability, cultural appropriateness and burden of technology use, as well as a cost-effectiveness analysis and a long-term benefit evaluation. The duration of the intervention will be 12 months, with another 24 months' post-trial long-term follow-up., Discussion: Our study is one of the first trials to evaluate the effect of an antibiotic stewardship programme in primary care settings in a low- or middle-income country (LMIC). All interventional activities will be designed to be embedded into routine primary care with strong local ownership. Through the trial we intend to impact on clinical practice and national policy in antibiotic prescription for primary care facilities in rural China and other LMICs., Trial Registration: ISRCTN, ID: ISRCTN96892547. Registered on 18 August 2019.

Urbanisation brings with it rapid socio-economic change with volatile livelihoods and unstable ownership of assets. Yet, current measures of wealth are based predominantly on static livelihoods found in rural areas. We sought to assess the extent to which seven common measures of wealth appropriately capture vulnerability to poverty in urban areas. We then sought to develop a measure that captures the characteristics of one urban area in Nepal. We collected and analysed data from 1,180 households collected during a survey conducted between November 2017 and January 2018 and designed to be representative of the Kathmandu valley. A separate survey of a sub set of households was conducted using participatory qualitative methods in slum and non-slum neighbourhoods. A series of currently used indices of deprivation were calculated from questionnaire data. We used bivariate statistical methods to examine the association between each index and identify characteristics of poor and non-poor. Qualitative data was used to identify characteristics of poverty from the perspective of urban poor communities which were used to construct an Urban Poverty Index that combined asset and consumption focused context specific measures of poverty that could be proxied by easily measured indicators as assessed through multivariate modelling. We found a strong but not perfect association between each measure of poverty. There was disagreement when comparing the consumption and deprivation index on the classification of 19% of the sample. Choice of short-term monetary and longer-term capital approaches accounted for much of the difference. Those who reported migrating due to economic necessity were most likely to be categorised as poor. A combined index was developed to capture these dimension of poverty and understand urban vulnerability. A second version of the index was constructed that can be computed using a smaller range of variables to identify those in poverty. Current measures may hide important aspects of urban poverty. Those who migrate out of economic necessity are particularly vulnerable. A composite index of socioeconomic status helps to capture the complex nature of economic vulnerability., Competing Interests: The authors have declared that no competing interests exist.

We describe the frequency of Zika and malaria among patients presenting with fever to secondary health facilities in Cross River State, Nigeria. Using a cross-sectional, stratified survey design, we randomly selected nine facilities and consecutively recruited 100 participants (aged ≥ 1 year) who presented with fever. On testing blood samples using Biocan qualitative lateral flow immuno-chromatographic cassettes for Zika IgG and IgM, 10% were seropositive for Zika virus (ZIKV) IgM, 12% for ZIKV IgG and 20% for ZIKV IgM, IgG or both. Following microscopy of thick films stained with Giemsa for malaria parasites, 55% were positive for malaria and 15% were positive for both malaria and ZIKV IgM, IgG or both. A moderately negative association between urban and rural household location and seropositivity for ZIKV IgM or IgG was found on logistic regression. Our results clearly indicate a high rate of probable ZIKV and malaria co-incidence in Cross River State. Given the high risk of serious fetal outcomes following ZIKV infection, further epidemiological research and surveillance systems for ZIKV are clearly required.

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.)

Background: Treatment non-adherence is a serious challenge to effective tuberculosis (TB) control in Tibet. In this study we will pilot and evaluate the effectiveness of using new electronic monitors (e-monitors) and a smartphone app to improve treatment adherence among new pulmonary TB patients in Tibet., Methods: We will use a multicentre, parallel-group, individually randomised controlled, superiority trial with blinded outcome evaluation and unblinded treatment. We will randomise new pulmonary TB outpatients (aged ≥ 15 years old and free from communication impairment) from Shigatse, Tibet to either the intervention or control arm in a 1:1 ratio at the time of their diagnosis. All patients will be treated according to the World Health Organisation standard 6-month TB treatment regimen and the China National TB programme guidelines. Intervention arm patients will be given their medication via e-monitors that have automatic voice reminders, and record medication adherence data and share it with health staff via Cloud connection. Intervention patients will also be encouraged to receive smartphone-based video-observed treatment if their adherence is problematic. Control arm patients will receive their medication in e-monitors that will collect medication adherence history, but will have their reminder function deactivated and are not linked to the app. The primary outcome is the rate of poor adherence, measured monthly during treatment as a binary indicator where poor adherence means missing ≥ 20% of doses in a month. We will conduct a qualitative process evaluation to explore operational questions regarding acceptability, cultural appropriateness and burden of technology use, as well as a cost-effectiveness analysis and an analysis of the long-term effects of the intervention on TB control., Discussion: Our study is one of the first trials to evaluate the use of e-monitors and smartphone apps for customised treatment support in low- and middle-income countries (LMICs). All intervention activities are designed to be embedded into routine TB care with strong local ownership. Through the trial we intend to understand the feasibility of our intervention, its effectiveness, its cost-effectiveness and its long-term impacts to inform future scale-up in remote areas of China and other LMICs., Trial Registration: Current Controlled Trials, ID: ISRCTN52132803 . Registered on 9 November 2018.

Background: In Nigeria, recent reports suggest that dengue viruses could be a major cause of acute fevers. We sought to make a cross-sectional estimate of the prevalence of current and previous dengue infections in patients presenting with fever to healthcare centres in Cross River State Nigeria., Methodology/principal Findings: This cross-sectional health facility survey recruited persons with temperature ≥38°C. Dengue virus immunoglobulin M (IgM)/immunoglobulin G (IgG) antibody testing using Onsite Duo dengue Ag-IgG/IgM lateral flow immunoassay cassettes was done. Samples which tested positive were further confirmed using the RecombiLISA dengue IgM and IgG enzyme linked immunosorbent assay kits and classified into primary and secondary dengue infection. Malaria testing was carried out using microscopy. Between 4 January 2017 and 24 August 2017 a total of 420 participants were sampled across 11 health centres. The mean age was 34 (range = 1-99), 63% were female, 49% reported sleeping under a treated mosquito net in the past week and 44% reported taking an antimalarial prior to seeking care. The mean number of days fever was present prior to seeking care was 8, and many of the participants presented with symptoms indicative of respiratory or urinary tract infections. Testing indicated that 6% (95% CI: 2, 13; n = 24) had either a primary or secondary dengue infection with or without co-existing malaria, while 4% (95% CI: 2, 9; n = 16) had either a primary or secondary dengue infection without co-existing malaria. 52% (95% CI: 46, 58; n = 218) had a malaria infection with or without any dengue infection, and 50% (95% CI: 44, 57; n = 210) had a malaria infection without any dengue infection., Conclusion: Our study confirms the presence of dengue at not insignificant levels in patients attending health centres with fever in this south eastern province of Nigeria. These data highlight the danger of the common presumption in this setting that fever is due to malaria. Surveillance for dengue is vital in this setting., Competing Interests: This research was funded by a research grant by AstraZeneca BioPharmaceutical company (https://www.astrazeneca.com/) awarded to two of the co-authors. AstraZeneca did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. We confirm that this does not alter our adherence to all PLOS ONE policies on sharing data and materials as detailed online in the PLOS ONE guide for authors http://journals.plos.org/plosone/s/competing-interests.

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.)

Following publication of the original article [1], the authors requested a correction be made, indicating L. Bates as the first author only. There is no joint first authorship.

Background: We developed a multifaceted intervention to reduce antibiotic prescription rate for children with upper respiratory tract infections (URTIs) among primary care doctors in township hospitals in China. The intervention achieved a 29% (95% CI 16-42) absolute risk reduction in antibiotic prescribing. This study was to assess the cost-effectiveness of our intervention at reducing antibiotic prescribing in rural primary care facilities as measured by the intervention's effect on the antibiotic prescription rates for childhood URTIs., Methods: We took a healthcare provider perspective, measuring costs of consultation (time cost of doctor), prescription monitoring process and peer-review meetings (time cost of participants) and medication costs. Costs on provider side were collected through a bespoke questionnaire from all 25 township hospitals in December 2016, while medication costs were collected prospectively in the trial. Incremental cost-effectiveness ratios were calculated by dividing the mean difference in cost of the two trial arms by the mean difference in antibiotic prescribing rate., Results: This showed an incremental cost of $0.03 per percentage point reduction in antibiotic prescribing. In addition to this incremental cost, the cost of implementing the intervention, including training and materials delivered by township hospitals, was $390.65 (SD $145.68) per healthcare facility., Conclusions: This study shows that a multifaceted intervention programme, when embedded into routine practice, is very cost-effective at reducing antibiotic prescribing in primary care facilities and has the potential of scale up in similar resource limited settings., (© 2018 John Wiley & Sons Ltd.)

Background: Maintaining quality of care in family planning (FP) counselling in low-resource settings is challenging. Job aids can help providers give more accurate and client-specific advice but require a provider to use them effectively and consistently. Marie Stopes International (MSI) have designed the tablet-computer based Digital Counselling Application (DCA), which prompts structured, supportive, client-specific and unbiased FP counselling. We hypothesise that a systematic exploration of clients' fertility intentions, medical eligibility and preferences will increase their uptake of long acting and permanent methods of contraception (LAPMs)., Methods/design: We will conduct a two-armed, parallel, cluster randomised control trial across all MSI clinics (clusters) in Ethiopia (24) and Vietnam (11), randomising 18 clinics to the intervention group and 17 to the control group. Intervention providers will attend a two-day DCA-use training programme, and use DCA in their FP counselling sessions. Usual care providers will counsel clients as before. We aim to recruit 75 clients who have had FP counselling per clinic (2625 total), following them up via two telephone interviews, initially within 2 days and then at 4 months. The primary outcome is defined as the proportion of clients who report choosing a LAPM following FP counselling and will include switchers (FP counselling clients who switch from using any other FP method) and adopters (FP counselling clients who adopt any FP method having not previously been using one). We will also collect secondary outcomes at the initial follow-up (including the proportion of clients reporting being recommended a LAPM by a provider and a range of measures of client experience and satisfaction) and at the 4-month follow-up (including a range of measures of continuation rates for different FP method types). In the intervention arm, we will also conduct mixed-methods sampling to assess how providers use DCA (using an observational survey of provider-client interactions), and understand users' experiences of receiving and giving DCA-based FP counselling (through in-depth interviews)., Discussion: This trial will provide novel information on the feasibility and acceptability of health worker delivered FP counselling using DCA, with robust evidence on its effectiveness at increasing the uptake of LAPMs in low-resource settings., Trial Registration: ISRCTN, ISRCTN11040557 . Registered on 2 March 2017 (retrospectively registered).