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Background In Pakistan, a smartphone-based telemonitoring (TM) program (Raabta) has been designed to support pregnant women with high risk for preeclampsia (HRPE) in Pakistan. However, implementing TM interventions is often challenging, particularly in low-resource settings, given the complexity of healthcare environments and variations in public and private health sectors. This study explores the potential barriers and facilitators for a sustained implementation of the Raabta program in public and private sector hospitals in Pakistan. Methods Using a qualitative description design, 57 semi-structured interviews with a diverse group of participants including patients from the public ( n = 15) and private sector hospitals ( n = 17), obstetricians from the public ( n = 5) and private sector hospitals ( n = 7), decision-makers ( n = 7) and telehealth experts ( n = 6). Participants were recruited using purposive and snowball sampling techniques. Interview transcripts were deductively analyzed using the Consolidated Framework for Implementation Research (CFIR) domains. Results Based on the CFIR domains, the findings included: (1) Raabta being perceived as user-friendly even for patients with low digital and language literacy; (2) Outer settings: Limited health and digital literacy, poor language proficiency, and cultural norms can influence the willingness and ability of public sector patients to use the Raabta; (3) Inner settings: The private health sector is well-equipped for the Raabta implementation, while the public health sector faces challenges related to physical space, limited human and financial resources, and physician resistance; (4) Individual characteristics: Majority participants demonstrated positive attitudes toward the Raabta program and expressed confidence in using it (5) Process: Recommendations included adopting a nurse-led model for the private sector, leveraging paramedics for monitoring the Raabta dashboard, integrating Raabta with existing digital platforms, and establishing an advisory committee for program sustainability. Conclusion Raabta implementation may be more feasible in the private sector due to patient demographics, health and digital literacy, cultural norms, financial resources, physician readiness, and hospital infrastructure.

Objective To describe presenting diagnoses and rates and causes of death by age category and sex among children with acute illness brought to a district headquarter hospital in Pakistan.Design Prospective cohort study.Setting Sanghar district headquarter hospital, Sindh, Pakistan between December 2019 and April 2020 and August 2020 and December 2020.Participants 3850 children 0–14 years presenting with acute illness to the emergency and outpatient departments and 1286 children admitted to the inpatient department.Outcome measures The primary outcome was Global Burden of Disease diagnosis category. Secondary outcomes were 28-day mortality rate, cause of death and healthcare delays, defined as delay in care-seeking, delay in reaching the healthcare facility and delay in appropriate treatment.Results Communicable diseases were the most common presenting diagnoses among outpatients and among inpatients aged 1 month to 9 years. Non-communicable diseases and nutritional disorders were more common with increasing age. Few children presented with injuries. Newborn period (age

Abstract Background Family planning (FP) interventions have improved the use of modern contraceptives, yet a high unmet need for contraception still exists in South Asia. This systematic review of existing research was conducted to identify effective FP interventions that led to an increase in the uptake of modern methods of contraception in South Asia. Methods Five electronic databases were searched for relevant studies published between January 1st, 2000 and May 4, 2023. Experimental studies that reported data on the impact of FP interventions on modern contraceptive use among women of reproductive age (15–49 years) in the South Asian region were included. A random-effects Inverse Variance weighted model was employed to pool the adjusted odds ratio (OR) on modern contraceptive use and unmet need for contraception. In addition, we computed subgroup meta-estimates based on intervention type and the urban-rural divide. Results Among 643 studies identified, 21 met the inclusion criteria. The overall pooled odds ratio for modern contraceptive use was significantly higher (OR 1.51; 95% CI 1.35–1.70; heterogeneity; I2 = 81%) for FP interventions with a significant reduction in unmet need for contraception (OR 0.86; 95% CI 0.78–0.94, I2 = 50%). The subgroup analysis revealed demand-generation (OR 1.61; 95% CI 1.32–1.96), health system integrated (OR 1.53; 95% CI 1.07–2.20), and franchised FP clinic interventions (OR 1.32; 95% CI 1.21–1.44) had promoted the modern contraceptive uptake. Further, FP interventions implemented in urban settings showed a higher increase in modern contraceptive use (OR 1.73; 95% CI 1.44–2.07) compared to rural settings (OR 1.46; 95% CI 1.28–1.66). Given the considerable heterogeneity observed across studies and the low degree of certainty indicated by the GRADE summary for the primary outcome, caution is advised when interpreting the results. Conclusion The review collated experimentally evaluated FP interventions that increased modern contraception use and reduced the unmet need in South Asia. The demand generation interventions were the most effective in increasing the uptake of modern contraceptive methods. Furthermore, the urban environment provides a conducive environment for interventions to improve contraceptive usage. However, further studies should assess which aspects were most effective on attitudes towards contraception, selection of more effective methods, and contraceptive behaviors.

Abstract Background The Three Delays Framework was instrumental in the reduction of maternal mortality leading up to, and during the Millennium Development Goals. However, this paper suggests the original framework might be reconsidered, now that most mothers give birth in facilities, the quality and continuity of the clinical care is of growing importance. Methods The paper explores the factors that contributed to maternal deaths in rural Pakistan and Mozambique, using 76 verbal autopsy narratives from the Community Level Interventions for Pre-eclampsia (CLIP) Trial. Results Qualitative analysis of these maternal death narratives in both countries reveals an interplay of various influences, such as, underlying risks and comorbidities, temporary improvements after seeking care, gaps in quality care in emergencies, convoluted referral systems, and arrival at the final facility in critical condition. Evaluation of these narratives helps to reframe the pathways of maternal mortality beyond a single journey of care-seeking, to update the categories of seeking, reaching and receiving care. Conclusions There is a need to supplement the pioneering “Three Delays Framework” to include focusing on continuity of care and the “Four Critical Connection Points”: (1) between the stages of pregnancy, (2) between families and health care workers, (3) between health care facilities and (4) between multiple care-seeking journeys. Trial registration NCT01911494, Date Registered 30/07/2013.

The use of modern contraceptive methods (MCMs) has been stagnant for the last decade in Pakistan. The second most populous province, Sindh reports 25% of MCMs use. Various factors including demographics and health services utilization are associated with the uptake of family planning services. This research aimed to identify and assess specific predictors of MCMs among women aged 15-49 in two districts of Sindh-Matiari and Badin. A cross-sectional household survey was conducted from October 2020- December 2020. In total, 1684 Married Women of Reproductive Age (MWRA) 15-49 years were interviewed. For the selection of eligible respondents, a two-stage stratified cluster sampling strategy was used. Univariate and multivariable logistic regression was used to determine the predictors for the use of MCM. Use of modern methods of contraceptive was 26.1% (n = 441). Statistically significant socio demographic predictors of MCM included: number of children 4 or more (AOR: 5.23; 95%CI: 2.78-9.84), mother having primary education (AOR: 1.73; 95% CI: 1.26-2.36), and husband having middle education (AOR: 1.69; 95% CI: 1.03-2.76). Maternal health services indicators included: postnatal care of mother (AOR: 1.46; 95% CI: 1.09-2.05); women who were visited by Lady Health Workers in their postnatal period and were counselled on family planning (AOR: 1.83; 95% CI: 1.38-2.42). Since the primary purpose of using modern contraceptive methods is for limiting pregnancies, there is a potential to promote awareness about the benefits of birth spacing as part of implementing a more integrated approach to family planning. The integration of family planning services within maternal and newborn child healthcare services effectively promote the voluntary adoption of modern contraceptive methods. The role of Lady Health Workers in family planning counseling and service provision and uptake is important in the context of Sindh and should be fostered further by opportunities for capacity building and their empowerment.

Purpose Conduct six systematic reviews investigating for-profit private sector roles in NCD prevention and management in low- and middle-income countries (LMICs) through our a priori framework’s pillars. Methods Six systematic reviews and thematic syntheses were performed between March-August 2021, Six databases, websites of relevant organizations, and references lists of included studies were comprehensively searched. Studies published in English from 2000 onwards involving the pillar of interest, for-profit private sector, NCD prevention/management, and LMIC context were included. Results were synthesized using an inductive thematic synthesis approach. Results Ultimately, 25 articles were included in the PPP review, 33 in Governance and Policy, 22 in Healthcare Provision, 15 in Innovation, 14 in Knowledge Educator, and 42 in Investment and Finance. The following themes emerged: PPPs (coordination; financial resources; provision; health promotion; capacity building; innovation; policy); Governance/Policy (lobbying; industry perception; regulation); Healthcare Provision (diagnosis/treatment; infrastructure; availability/accessibility/affordability); Innovation (product innovation; process innovation; marketing innovation; research; innovation dissemination); Knowledge Educator (training; health promotion; industry framework/guideline formation); Investment and Finance (treatment cost; regulation; private insurance; subsidization; direct investment; collaborative financing; innovative financing; research). Conclusion These findings will be instrumental for LMICs considering private sector engagement. Potential conflicts of interest must be considered when implementing private sector involvement.

Abstract Accurate estimation of gestational age is an essential component of good obstetric care and informs clinical decision-making throughout pregnancy. As the date of the last menstrual period is often unknown or uncertain, ultrasound measurement of fetal size is currently the best method for estimating gestational age. The calculation assumes an average fetal size at each gestational age. The method is accurate in the first trimester, but less so in the second and third trimesters as growth deviates from the average and variation in fetal size increases. Consequently, fetal ultrasound late in pregnancy has a wide margin of error of at least ±2 weeks’ gestation. Here, we utilise state-of-the-art machine learning methods to estimate gestational age using only image analysis of standard ultrasound planes, without any measurement information. The machine learning model is based on ultrasound images from two independent datasets: one for training and internal validation, and another for external validation. During validation, the model was blinded to the ground truth of gestational age (based on a reliable last menstrual period date and confirmatory first-trimester fetal crown rump length). We show that this approach compensates for increases in size variation and is even accurate in cases of intrauterine growth restriction. Our best machine-learning based model estimates gestational age with a mean absolute error of 3.0 (95% CI, 2.9–3.2) and 4.3 (95% CI, 4.1–4.5) days in the second and third trimesters, respectively, which outperforms current ultrasound-based clinical biometry at these gestational ages. Our method for dating the pregnancy in the second and third trimesters is, therefore, more accurate than published methods.

Objective: To map literature on research ethics committees, institutional review boards and ethics review framework in Pakistan to identify key insights during public health emergencies and normal times. Method: The systematic scoping review was conducted in April 22, and comprised literature search on PubMed, World Health Organisation Global Index Medicus and Summons databases for articles published between January 2005 and February 2022. Information extracted included authors’ names, year of publication, title, study methodology, and key insights under the heads of challenges and solutions. Due to data heterogeneity, key themes were identified and analysed. Results: Of the 2,190 studies initially identified, 21(0.95%) were subjected to full-text review, and, from among them, 9(45%) were analysed in detail. There were 4 key insights identified: research ethics committees and institutional review boards in Pakistan remain unregulated as they are currently not registered or accredited by a competent national-level authority; most members of such committees are not formally trained to implement the mandate; internal and external pressures hinder independent decision-making of such committees; and other issues hindering the functionality and performance of research ethics committees and institutional review boards. Conclusion: Despite existing publications calling for urgent policy and regulatory reforms, there is a dearth of literature and minimal policy actions underline the fact that ethics review remains a neglected area in Pakistan. Key Words: Ethics, Pakistan, Bioethics, Ethics committees, Institutional review board.

This study assessed the usability of the smartphone app, named “Raabta” from the perspective of pregnant women at high risk of preeclampsia to improve the Raabta app for future implementation. Think-aloud and task-completion techniques were used with a purposive sample of 14 pregnant women at high risk of preeclampsia. The sessions were audio-recorded and later professionally transcribed for thematic analysis. The study generated learnings associated with four themes: improving the clarity of instructions, messaging, and terminology; accessibility for non-tech savvy and illiterate Urdu users; enhancing visuals and icons for user engagement; and simplifying navigation and functionality. Overall, user feedback emphasized the importance of enhancing the clarity of instructions, messaging, and terminology within the Raabta app. Voice messages and visuals were valued by users, particularly among the non-tech savvy and illiterate Urdu users, as they enhance accessibility and enable independent monitoring. Suggestions were made to enhance user engagement through visual improvements such as enhanced graphics and culturally aligned color schemes. Lastly, users highlighted the need for improved navigation both between screens and within screens to enhance the overall user experience. The Raabta app prototype will be modified based on the feedback of the users to address the unique needs of diverse groups.

BackgroundUnmet need for family planning in Pakistan is high, with 17% of all married women wanting to avoid or delay pregnancy. However, they cannot owing to a lack of access to modern contraception and sociocultural hindrances. With the modern contraceptive prevalence rate stagnant at approximately 25% over the last 5 years, it is important to explore barriers and enablers to modern contraception uptake to reduce maternal and child mortality and improve reproductive health outcomes for young girls and women. ObjectiveA formative research approach was taken to explore community member and health care provider perspectives on access to and use of family planning methods in 2 rural districts of Sindh, Pakistan. The broader goal of this study was to provide evidence to design and implement a socioculturally appropriate family planning intervention within the existing service delivery platforms to increase modern contraceptive uptake in the context of rural Sindh. MethodsA qualitative exploratory design was used. Between October 2020 and December 2020, 11 focus group discussions and 11 in-depth interviews were conducted. Focus group discussions were held with men and women from the community, including adolescents, to build an understanding of community beliefs and concepts regarding modern contraceptive methods. In-depth interviews were conducted with health care workers and explored intersections between family planning and reproductive health service delivery at the facility and outreach levels. ResultsThe findings revealed that limited financial autonomy, restricted women’s mobility, discriminatory gender norms, and cultural practices left women with little opportunity for independent decision-making on the use of modern contraceptive methods. Furthermore, facility-level and supply-side barriers, including frequent stock-outs of modern contraceptives combined with a lack of capacity of health workers to provide quality family planning services and counseling, played an important role in demotivating women from seeking services. In addition, a lack of integration of family planning with maternal and child health service delivery at the health system level was emphasized as a major missed opportunity for contraceptive uptake. Several demand-side barriers to family planning uptake were also highlighted. These included husbands’ or in-laws’ disapproval, social stigma, and perceived fear of side effects regarding modern family planning method use. More importantly, a lack of adolescent-friendly reproductive health services and spaces for counseling was identified as a critical intervention area. ConclusionsThis study provides qualitative evidence on issues related to the effectiveness of family planning interventions, specifically in the context of rural Sindh. The findings emphasize the need to design socioculturally appropriate and health system–relevant family planning interventions—the effectiveness of which can be improved through their integration with maternal and child health service delivery mechanisms, consistent service provision, and opportunities for the capacity building of the health care workforce. International Registered Report Identifier (IRRID)RR2-10.2196/35291

Objectives Conduct a systematic review of existing frameworks to understand the for-profit private sector’s roles in non-communicable disease (NCD) control and management. Control includes population-level control measures that prevent NCDs and mitigate the magnitude of the NCD pandemic, and management includes treatment and management of NCDs. The for-profit private sector was defined as any private entities that make profit from their activities (ie, pharmaceutical companies, unhealthy commodity industries, distinct from not-for-profit trusts or charitable organisations).Design A systematic review and inductive thematic synthesis was performed. Comprehensive searches of PubMed, EMBASE, Cochrane Library, Web of Science, Business Source Premier and Proquest/ABI Inform were conducted on 15 January 2021. Grey literature searches were conducted on 2 February 2021 using the websites of 24 relevant organisations. Searches were filtered to only include articles published from the year 2000 onwards, in English. Articles that included frameworks, models or theories and the for-profit private sector’s role in NCD control and management were included. Two reviewers performed the screening, data extraction and quality assessment. Quality was assessed using the tool developed by Hawker et al for qualitative studies.Setting The for-profit private sector.Results There were 2148 articles initially identified. Following removal of duplicates, 1383 articles remained, and 174 articles underwent full-text screening. Thirty-one articles were included and used to develop a framework including six themes that outlined the roles that the for-profit private sector plays in NCD management and control. The themes that emerged included healthcare provision, innovation, knowledge educator, investment and financing, public–private partnerships, and governance and policy.Conclusion This study provides an updated insight on literature that explores the role of the private sector in controlling and monitoring NCDs. The findings suggest that the private sector could contribute, through various functions, to effectively manage and control NCDs globally.

Introduction High maternal mortality from pre-eclampsia/eclampsia results from lack of early identification and management of pregnant women at high-risk for pre-eclampsia. A potential tool to support pregnant women at high-risk for pre-eclampsia is telemonitoring. There is limited evidence on the use and effectiveness of telemonitoring for pregnant women in low-income and middle-income countries (LMICs) which limits the understanding of the process and mechanisms through which the intervention works in LMICs. This study will explore the feasibility of implementing a mobile phone-based telemonitoring programme for pregnant women at high-risk for pre-eclampsia in Karachi, Pakistan.Methods and analysis A convergent mixed-methods study will be conducted at the Jinnah Postgraduate Medical Center (JPMC) in Karachi, Pakistan. This study will recruit 50 pregnant women at high-risk for pre-eclampsia to assess clinical feasibility across the five foci of Bowen’s framework including acceptability, demand, implementation, practicality and limited-efficacy testing. Data sources will include semi-structured interviews with the enrolled women, caregivers and clinicians, as well as quantitative data from paper medical records, research logs and server data. The quantitative and qualitative data will be analysed separately and then integrated at the interpretation and reporting levels to advance our understanding of the telemonitoring programme’s feasibility across the five areas of Bowen’s framework.Ethics and dissemination Ethics approvals have been obtained from JPMC, the National Bioethics Committee of Pakistan, University Health Network, Aga Khan University and the University of Toronto. The study results will be disseminated to the scientific community through publications and conference presentations. Findings of the study will provide evidence on the feasibility of using a telemonitoring programme where pregnant women at high-risk for pre-eclampsia in Pakistan will take their own blood pressure readings at home. Lessons learnt in this feasibility trial will be used to determine the appropriateness of a future effectiveness trial.Trial registration number NCT05662696

Poliomyelitis is a condition of great concern and is endemic in only two countries of the world: Pakistan and Afghanistan. Community mobilization plays a vital role in raising awareness and can help reduce polio vaccine refusals. The objective of this study will be to decrease polio vaccine refusals and zero-dose vaccines by motivating behavior change through the provision of conditional–collective–community-based incentives (C3Is) based on a reduction in polio vaccine refusals. The project will adopt a pretest/post-test quasi-experimental design with two intervention high-risk union councils (HRUCs) and two control union councils (UCs) of peri-urban (Karachi) and rural (Bannu) settings in Pakistan. A participatory community engagement and demand creation strategy with trust-building community mobilization with C3Is, to reduce vaccine refusals and improve polio immunization coverage in two HRUCs, will be used. These UCs will be divided into clusters based on the polio program framework and community groups will be formed in each cluster. These community groups will carry out awareness activities and will be given serial targets to reduce vaccine refusals and those who qualify will be provided C3Is. The project intends to create a replicable model that the government can integrate within health systems for long-term sustainability until the goal of eradication of poliovirus is achieved. The evaluation will be carried out by an independent data collection and analysis team at baseline and endline (after 12 months of intervention). The trial is registered with linicalTrials.gov with number NCT05721274.

Background and Objective: Few data exist on trends in acute myocardial infarction (AMI) patterns spanning recent epidemiological shifts in low middle-income countries (LMICs). To understand temporal disease patterns of AMI characteristics and outcomes between 1988–2018, we used digitized legacy clinical data at a large tertiary care centre in Pakistan. Methods: We reviewed digital health information capture systems maintained across the Aga Khan University Hospital and obtained structured elements to create a master dataset. We included index admissions of patients >18 years that were discharged between January 1, 1988, and December 31, 2018, with a primary discharge diagnosis of AMI (using ICD-9 diagnoses). The outcome evaluated was in-hospital mortality. Clinical characteristics derived from the electronic database were validated against chart review in a random sample of cases ('k' 0.53–1.00). Results: The final population consisted of 14,601 patients of which 30.6% (n = 4,470) were female, 52.4% (n = 7,651) had ST elevation MI and 47.6% (n = 6,950) had non-ST elevation MI. The median (IQR) age at presentation was 61 (52–70) years. Overall unadjusted in-hospital mortality was 10.3%. Across the time period, increasing trends were noted for the following characteristics: age, proportion of women, prevalence of hypertension, diabetes, proportion with NSTEMI (all ptrend < 0.001). In-hospital mortality rates declined significantly between 1988–1997 and 2008–2018 (13.8% to 9.2%, p < 0.001). Conclusions: The patterns of AMI have changed over the last three decades with a concomitant decline in in-hospital mortality at a tertiary care centre in Pakistan. Clinical digitized data presents a unique opportunity for gaining insights into disease patterns in LMICs.

Introduction Health inequities are defined as unfair and avoidable differences in health between groups within a population. Most health research is conducted through observational studies, which are able to offer real-world insights about etiology, healthcare policy/programme effectiveness and the impacts of socioeconomic factors. However, most published reports of observational studies do not address how their findings relate to health equity. Our team seeks to develop equity-relevant reporting guidance as an extension of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. This scoping review will inform the development of candidate items for the STROBE-Equity extension. We will operationalise equity-seeking populations using the PROGRESS-Plus framework of sociodemographic factors. As part of a parallel stream of the STROBE-Equity project, the relevance of candidate guideline items to Indigenous research will be led by Indigenous coinvestigators on the team.Methods and analysis We will follow the Joanna Briggs Institute method for conducting scoping reviews. We will evaluate the extent to which the identified guidance supports or refutes our preliminary candidate items for reporting equity in observational studies. These candidate items were developed based on items from equity-reporting guidelines for randomised trials and systematic reviews, developed by members of this team. We will consult with our knowledge users, patients/public partners and Indigenous research steering committee to invite suggestions for relevant guidance documents and interpretation of findings. If the identified guidance suggests the need for additional candidate items, they will be developed through inductive thematic analysis.Ethics and dissemination We will follow a principled approach that promotes ethical codevelopment with our community partners, based on principles of cultural safety, authentic partnerships, addressing colonial structures in knowledge production and the shared ownership, interpretation, and dissemination of research. All products of this research will be published as open access.

Introduction South Africa’s evolving burden of disease is challenging due to a persistent infectious disease, burgeoning obesity, most notably among women and rising rates of non-communicable diseases (NCDs). With two thirds of women presenting at their first antenatal visit either overweight or obese in urban South Africa (SA), the preconception period is an opportunity to optimise health and offset transgenerational risk of both obesity and NCDs.Methods and analysis Bukhali is the first individual randomised controlled trial in Africa to test the efficacy of a complex continuum of care intervention and forms part of the Healthy Life Trajectories Initiative (HeLTI) consortium implementing harmonised trials in Canada, China, India and SA. Starting preconception and continuing through pregnancy, infancy and childhood, the intervention is designed to improve nutrition, physical and mental health and health behaviours of South African women to offset obesity-risk (adiposity) in their offspring. Women aged 18–28 years (n=6800) will be recruited from Soweto, an urban-poor area of Johannesburg. The primary outcome is dual-energy X-ray absorptiometry derived fat mass index (fat mass divided by height2) in the offspring at age 5 years. Community health workers will deliver the intervention randomly to half the cohort by providing health literacy material, dispensing a multimicronutrient supplement, providing health services and feedback, and facilitating behaviour change support sessions to optimise: (1) nutrition, (2) physical and mental health and (3) lay the foundations for healthier pregnancies and early child development.Ethics and dissemination Ethical approval has been obtained from the Human Ethics Research Committee University of the Witwatersrand, Johannesburg, South Africa (M1811111), the University of Toronto, Canada (19-0066-E) and the WHO Ethics Committee (ERC.0003328). Data and biological sample sharing policies are consistent with the governance policy of the HeLTI Consortium (https://helti.org) and South African government legislation (POPIA). The recruitment and research team will obtain informed consent.Trial registration This trial is registered with the Pan African Clinical Trials Registry (https://pactr.samrc.ac.za) on 25 March 2019 (identifier: PACTR201903750173871).Protocol version 20 March 2022 (version #4). Any protocol amendments will be communicated to investigators, Institutional Review Board (IRB)s, trial participants and trial registries.

BackgroundIndia launched the National Rural Health Mission (NRHM) in 2005 to strengthen its primary healthcare system in high-focus and northeast-focus states. One of the NRHM objectives was to reduce child undernutrition in India.Methods and findingsWe used data from 1992, 1998, 2005, and 2015 National Family Health Survey (NFHS) of India to evaluate trends in child undernutrition prevalence before and after NRHM and across different categories of focus states. Stunting, Wasting, and Comprehensive Index of Anthropometric Failure (CIAF) were assessed using the World Health Organization (WHO) growth curves to assess chronic, acute, and overall undernutrition. The study included 187,452 children aged 3 years or under. Survey-weighted and confounder-adjusted average annualized reduction rates (AARRs) and predicted probability ratios were used to assess trends and socioeconomic disparities for child undernutrition, respectively. Nationwide, the prevalence of all types of undernutrition decreased from 1992 to 2015. However, the trends varied before and after NRHM implementation and differentially by focus states. After NRHM, acute undernutrition declined more rapidly among high-focus states (AARR 1.0%) but increased in normal-focus states (AARR -1.9% per year; p-value for the difference ConclusionsOur results suggests that NRHM implementation might be associated with improvement in wasting (acute) rather than stunting (chronic) forms of undernutrition. Strategies to combat undernutrition equitably, especially in high-focus states, are needed.

BackgroundThe uptake of modern contraceptive methods (MCMs) remains low, with 25% of women reporting their use in Pakistan. The overarching interventions covering service delivery platforms at facility and community levels necessitate the integration of family planning (FP) with maternal, newborn, and child health (MNCH) services. ObjectiveThe main aim of this study is to evaluate the impact of an integrated FP-MNCH service delivery model to increase coverage of MCMs in rural Pakistan. Moreover, we aim to measure the level of effectiveness of interventions regarding the uptake of MCMs. MethodsA quasi-experimental, sequential, mixed methods study design with pre- and postevaluation will be adopted to evaluate the impact of integration of FP with MNCH services. The interventions include the following: (1) capacity strengthening of health care providers, including technical trainings; training in counseling of women who attend immunization centers, antenatal care (ANC) clinics, and postnatal care (PNC) clinics; and provision of job aids; (2) counseling of women and girls attending ANC, PNC, and pediatric clinics; (3) ensuring sustained provision of supplies and commodities; (4) community engagement, including establishing adolescent-friendly spaces; and (5) use of District Health Information System data in decision-making. Descriptive statistics will be used to estimate prevalence (ie, proportions) and frequencies of outcome indicators. A univariate difference-in-difference analytical approach will be used to estimate the effect of the interventions. In addition, a Blinder-Oaxaca decomposition analysis will be conducted to identify and quantify determinants of the modern contraceptive prevalence rate. ResultsThe intervention phase began in July 2021 and will run until June 2022. The impact assessment will be conducted from July to September 2022. ConclusionsThis project will evaluate the impact of integrating FP with MNCH services. Furthermore, this study will identify the drivers and barriers in uptake of MCMs and will simultaneously help in modifying the interventional strategies that can be scaled up through existing service delivery platforms within the public and private sectors, according to the local sociocultural and health system context. Trial RegistrationClinicalTrials.gov NCT05045599; https://clinicaltrials.gov/ct2/show/NCT05045599 International Registered Report Identifier (IRRID)DERR1-10.2196/35291

BackgroundLack of early risk detection, diagnosis, and treatment of pregnant women at high risk for pre-eclampsia can result in high maternal mortality and morbidity not only in Pakistan but also in other low- to middle-income countries (LMICs). A potential tool for supporting pregnant women at high risk for pre-eclampsia for early detection is telemonitoring (TM). However, there is a limited body of evidence on end-user needs and preferences to inform the design of the TM programs for pregnant women at high risk for pre-eclampsia, specifically in LMICs such as Pakistan. ObjectiveThis study aims to explore the needs of TM for pregnant women at high risk for pre-eclampsia in Karachi, Pakistan, to inform a potential future feasibility trial of a mobile phone–based TM program. MethodsAn interpretive qualitative description approach was used to conduct and analyze 36 semistructured interviews with 15 (42%) pregnant women and 21 (58%) key informants, including clinicians; nurses; maternal, neonatal, and child health specialists; and digital health experts to explore the perspectives, needs, and preferences of a mobile phone–based TM program to support pregnant women at high risk for pre-eclampsia. Pregnant women were identified through heterogeneous sampling, whereas key informants were selected through purposive sampling. The interview transcripts were analyzed using a conventional content analysis technique. ResultsThe following four themes emerged from the analysis of the transcripts: poor use of antenatal care during pregnancy, the value of a TM program in high-risk pregnancy, barriers influencing the adoption of TM programs and potential strategies, and considerations for implementing TM programs. The pregnant women and health care providers were willing to use a TM program as they perceived many benefits, including early identification of pregnancy complications, prompt treatment, convenience, cost-effectiveness, increased sense of empowerment for one’s health care, improved care continuity, and reduced clinical workload. However, some providers and pregnant women mentioned some concerns regarding the adoption of a TM program, including malfunctioning and safety concerns, potential inaccuracy of blood pressure machines, increased clinical workload, and resistance to learning new technology. Our study recommends building the capacity of patients and providers on TM program use, sensitizing the community and family members on the usefulness of the TM program, using an approach incorporating user-centered design and phased implementation to determine the clinical workload and whether additional staff for the TM program is required, and ensuring greater levels of co-design and the engagement of consumer representatives. ConclusionsOur findings highlight the perceived feasibility of a mobile phone–based TM program for pregnant women at high risk for pre-eclampsia and provide insights that can be directly used for the design of future TM programs with the aim of reducing mortality and morbidity from pre-eclampsia and eclampsia in LMICs.

Abstract Diarrheal disease, still a major cause of childhood illness, is caused by numerous, diverse infectious microorganisms, which are differentially sensitive to environmental conditions. Enteropathogen‐specific impacts of climate remain underexplored. Results from 15 studies that diagnosed enteropathogens in 64,788 stool samples from 20,760 children in 19 countries were combined. Infection status for 10 common enteropathogens—adenovirus, astrovirus, norovirus, rotavirus, sapovirus, Campylobacter, ETEC, Shigella, Cryptosporidium and Giardia—was matched by date with hydrometeorological variables from a global Earth observation dataset—precipitation and runoff volume, humidity, soil moisture, solar radiation, air pressure, temperature, and wind speed. Models were fitted for each pathogen, accounting for lags, nonlinearity, confounders, and threshold effects. Different variables showed complex, non‐linear associations with infection risk varying in magnitude and direction depending on pathogen species. Rotavirus infection decreased markedly following increasing 7‐day average temperatures—a relative risk of 0.76 (95% confidence interval: 0.69–0.85) above 28°C—while ETEC risk increased by almost half, 1.43 (1.36–1.50), in the 20–35°C range. Risk for all pathogens was highest following soil moistures in the upper range. Humidity was associated with increases in bacterial infections and decreases in most viral infections. Several virus species' risk increased following lower‐than‐average rainfall, while rotavirus and ETEC increased with heavier runoff. Temperature, soil moisture, and humidity are particularly influential parameters across all enteropathogens, likely impacting pathogen survival outside the host. Precipitation and runoff have divergent associations with different enteric viruses. These effects may engender shifts in the relative burden of diarrhea‐causing agents as the global climate changes.

Abstract Background In recent decades, the prevalence of obesity in children has increased dramatically. This worldwide epidemic has important consequences, including psychiatric, psychological and psychosocial disorders in childhood and increased risk of developing non-communicable diseases (NCDs) later in life. Treatment of obesity is difficult and children with excess weight are likely to become adults with obesity. These trends have led member states of the World Health Organization (WHO) to endorse a target of no increase in obesity in childhood by 2025. Main body Estimates of overweight in children aged under 5 years are available jointly from the United Nations Children’s Fund (UNICEF), WHO and the World Bank. The Institute for Health Metrics and Evaluation (IHME) has published country-level estimates of obesity in children aged 2–4 years. For children aged 5–19 years, obesity estimates are available from the NCD Risk Factor Collaboration. The global prevalence of overweight in children aged 5 years or under has increased modestly, but with heterogeneous trends in low and middle-income regions, while the prevalence of obesity in children aged 2–4 years has increased moderately. In 1975, obesity in children aged 5–19 years was relatively rare, but was much more common in 2016. Conclusions It is recognised that the key drivers of this epidemic form an obesogenic environment, which includes changing food systems and reduced physical activity. Although cost-effective interventions such as WHO ‘best buys’ have been identified, political will and implementation have so far been limited. There is therefore a need to implement effective programmes and policies in multiple sectors to address overnutrition, undernutrition, mobility and physical activity. To be successful, the obesity epidemic must be a political priority, with these issues addressed both locally and globally. Work by governments, civil society, private corporations and other key stakeholders must be coordinated.

It is unclear whether the sequence and timing of early life neurodevelopment varies across human populations, excluding the effects of disease or malnutrition. Here, the authors show that children of healthy, urban, educated mothers show very similar development across five geographically diverse populations.

Background: PIERS on the Move (POM) is a mobile health application developed to support community health workers identification and management of women at risk of adverse outcomes from pre-eclampsia. The objective of this study was to evaluate the impact of using POM in Pakistan on Lady Health Workers' (LHWs) knowledge and self-efficacy related to caring for women with pre-eclampsia, and their perception of usefulness of the tool.Methodology: An evaluation was designed for health care workers involved in the Community-Level Intervention for Pre-eclampsia (CLIP) cluster randomized trial from 2014 to 2016 in Sindh Province, Pakistan (NCT01911494). A semi-structured focus group guide was developed based on the Technology Acceptance Model (TAM), which theorizes that an individual's behavioral intention to use a system is determined by perceived usefulness and ease of use. Preliminary qualitative analysis was undertaken by the Pakistan and Canadian teams to create a coding framework for full qualitative analysis, which was completed using NVivo12.Results: Three key informant interviews were conducted with two Lady Health Supervisors and one Senior Medical Officer. Sixty-two LHWs were included in three focus group discussions. LHWs found the POM app easy to use and useful for their work as a helpful repository for maternal health information and guiding counseling and management of pre-eclampsia. LHWs reported increased knowledge and confidence in their work. Availability of clinical homecare, including postpartum, was felt to positively impact healthcare provided to pregnant and postpartum women. Potential community level impacts included strengthening relationships between health care providers and communities and between LHWs and the health system. LHWs shared reports of earlier care-seeking and increased awareness of maternal health issues by community members.Conclusions: LHWs carry a large burden of responsibility for community health in rural Pakistan and appreciated the investment in their skills and capacity during the CLIP trial with the POM app. Investing in communications technology for community health workers through improved referrals and follow up may strengthen cohesiveness of the health system overall.

BackgroundGestational hypertensive and acute hypotensive disorders are associated with maternal morbidity and mortality worldwide. However, physiological blood pressure changes in pregnancy are insufficiently defined. We describe blood pressure changes across healthy pregnancies from the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) Fetal Growth Longitudinal Study (FGLS) to produce international, gestational age-specific, smoothed centiles (third, 10th, 50th, 90th, and 97th) for blood pressure.Methods and findingsSecondary analysis of a prospective, longitudinal, observational cohort study (2009 to 2016) was conducted across 8 diverse urban areas in Brazil, China, India, Italy, Kenya, Oman, the United Kingdom, and the United States of America. We enrolled healthy women at low risk of pregnancy complications. We measured blood pressure using standardised methodology and validated equipment at enrolment at 14 mmHg or diastolic blood pressure by >11 mmHg in fewer than 10% of women at any gestational age. Fewer than 10% of women increased their systolic blood pressure by >24 mmHg or diastolic blood pressure by >18 mmHg at any gestational age. The study's main limitations were the unavailability of prepregnancy blood pressure values and inability to explore circadian effects because time of day was not recorded for the blood pressure measurements.ConclusionsOur findings provide international, gestational age-specific centiles and limits of acceptable change to facilitate earlier recognition of deteriorating health in pregnant women. These centiles challenge the idea of a clinically significant midpregnancy drop in blood pressure.

Background:Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. Health research is crucial to managing disease burden. Previous work has highlighted marked discrepancies in research output and disease burden between high-income countries (HICs) and low- and lower-middle-income countries (LI-LMICs) and there is little data to understand whether this gap has bridged in recent years. We conducted a global, country level bibliometric analysis of CVD publications with respect to trends in disease burden and county development indicators. Methods:A search filter with a precision and recall of 0.92 and 0.91 respectively was developed to extract cardiovascular publications from the Web of Science (WOS) for the years 2008–2017. Data for disease burden and country development indicators were extracted from the Global Burden of Disease and the World Bank database respectively. Results:Our search revealed 847,708 CVD publications for the period 2008–17, with a 43.4% increase over the decade. HICs contributed 81.1% of the global CVD research output and accounted for 8.1% and 8.5% of global CVD DALY losses deaths respectively. LI-LMICs contributed 2.8% of the total output and accounted for 59.5% and 57.1% global CVD DALY losses and death rates. Conclusions:A glaring disparity in research output and disease burden persists. While LI-LMICs contribute to the majority of DALYs and mortality from CVD globally, their contribution to research output remains the lowest. These data call on national health budgets and international funding support to allocate funds to strengthen research capacity and translational research to impact CVD burden in LI-LMICs.

Background Breast feeding in conflict settings is known to be the safest way to protect infant and young children from malnourishment and increased risk of infections. This systematic review assesses the evidence on infant and young child feeding (IYCF) practices in conflict settings.Methodology We conducted a search in PubMed and CENTRAL and also searched for grey literature from the year 1980 to August 2019. We included studies conducted in settings inflicted with armed conflict; which comprised settings undergoing conflict, as well as, those within 5 years of its cessation. Studies were included if they discussed IYCF practices, barriers, programmes and guidelines to promote and improve IYCF practices. Two review authors independently evaluated and screened studies for eligibility and extracted data; followed by a descriptive and thematic analysis.Results We included 56 studies in our review including 11 published articles and 45 reports from grey literature and broadly classified into four predetermined sections: epidemiology (n=24), barriers/enablers (n=18), programmes/interventions (n=15) and implementation guidelines (n=30). Epidemiological evidence shows that IYCF practices were generally poor in conflict settings with median prevalence of exclusive breast feeding at 25%, continued breast feeding at 29%, bottle feeding at 58.3%, introduction to solid, semisolid or soft foods at 71.1% and minimum dietary diversity at 60.3%.IYCF practices were affected by displacement, stress, maternal malnutrition and mental health, family casualties and free distribution of breast milk substitutes. To improve IYCF, several interventions were implemented; including, training of health workers, educating mothers, community networking and mobilisation, lactation-support service, baby friendly hospital initiative, mother–baby friendly spaces and support groups.Conclusion The evidence suggests that IYCF practices are generally poor in conflict inflicted settings. However, there is potential for improvement by designing effective interventions, responsibly disseminating, monitoring and implementing IYCF guidelines as prescribed by WHO development partners, government and non-government organisations with dedicated funds and investing in capacity development.

Culture-independent diagnostics have revealed a larger burden of Shigella among children in low-resource settings than previously recognized. We further characterized the epidemiology of Shigella in the first two years of life in a multisite birth cohort. We tested 41,405 diarrheal and monthly non-diarrheal stools from 1,715 children for Shigella by quantitative PCR. To assess risk factors, clinical factors related to age and culture positivity, and associations with inflammatory biomarkers, we used log-binomial regression with generalized estimating equations. The prevalence of Shigella varied from 4.9%-17.8% in non-diarrheal stools across sites, and the incidence of Shigella-attributable diarrhea was 31.8 cases (95% CI: 29.6, 34.2) per 100 child-years. The sensitivity of culture compared to qPCR was 6.6% and increased to 27.8% in Shigella-attributable dysentery. Shigella diarrhea episodes were more likely to be severe and less likely to be culture positive in younger children. Older age (RR: 1.75, 95% CI: 1.70, 1.81 per 6-month increase in age), unimproved sanitation (RR: 1.15, 95% CI: 1.03, 1.29), low maternal education (

Introduction Pakistan has a high burden of maternal, newborn and child morbidity and mortality. Several factors including weak scale-up of evidence-based interventions within the existing health system; lack of community awareness regarding health conditions; and poverty contribute to poor outcomes. Deaths and morbidity are largely preventable if a combination of community and facility-based interventions are rolled out at scale.Methods and analysis Umeed-e-Nau (UeN) (New Hope) project aims is to improve maternal, newborn and child health (MNCH) in eight high-burden districts of Pakistan by scaling up of evidence-based interventions. The project will assess interventions focused on, first, improving the quality of MNCH care at primary level and secondary level. Second, interventions targeting demand generation such as community mobilisation, creating awareness of healthy practices and expanding coverage of outreach services will be evaluated. Third, we will also evaluate interventions targeting the improvement in quality of routine health information and promotion of use of the data for decision-making. Hypothesis of the project is that roll out of evidence-based interventions at scale will lead to at least 20% reduction in perinatal mortality and 30% decrease in diarrhoea and pneumonia case fatality in the target districts whereas two intervention groups will serve as internal controls. Monitoring and evaluation of the programme will be undertaken through conducting periodical population level surveys and quality of care assessments. Descriptive and multivariate analytical methods will be used for assessing the association between different factors, and difference in difference estimates will be used to assess the impact of the intervention on outcomes.Ethics and dissemination The ethics approval was obtained from the Aga Khan University Ethics Review Committee. The findings of the project will be shared with relevant stakeholders and disseminated through open access peer-reviewed journal articles.Trial registration number NCT04184544; Pre-results.

Abstract Background The availability of resources, knowledge, and will to expand access to high-quality emergency care in low- and middle-income countries has made strong progress in recent years. While the possibility for intervention has improved, the need has only grown more pressing. What remains is for us, the people who practice and support emergency care delivery on a regular basis, to pull these elements together and present a cohesive call to action for leaders to prioritize the development of emergency care. This advocacy should coalesce around two high-level commitments: the Sustainable Development Goals and Universal Health Coverage. Emergency care has not been a traditional tool that policy makers rely on to improve health and development; however, we can show that it is actually critical to achieving these goals. Making this case has become possible with the availability of evidence that shows emergency health conditions contribute to a substantial portion of the disease burden, emergency care interventions are high-impact, and the interventions can be implemented without a substantial increase in resources. Main body There is a growing understanding of the burden of disease in low- and middle-income countries and how 54% or 24.3 million deaths are amenable to emergency care systems. There are a group of diseases that are time sensitive and show improved outcomes with good emergency care systems. Alongside an improving scientific underpinning to emergency care, there is growing policy recognition. While there is no direct mention of emergency care in the Sustainable Development Goals document, many goals, such as reductions in infant and maternal deaths, deaths due to non-communicable diseases, road traffic injuries and violence, improving resilience of climate change, universal coverage, and safe/sustainable urban environments are not achievable without developing, sustaining, and improving the quality of emergency care systems. Conclusion To take emergency care to the next level, we must capitalize on the growing understanding of the disease burden of emergent conditions, along with the increasing evidence of the high-impact and low-cost of emergency care interventions. Linking these messages to widely accepted policy priorities like the SDGs and UHC will increase attention towards the development of emergency care systems, which potentially could save lives.

Abstract Background Hypertensive disorders are the second highest direct obstetric cause of maternal death after haemorrhage, accounting for 14% of maternal deaths globally. Pregnancy hypertension contributes to maternal deaths, particularly in low- and middle-income countries, due to a scarcity of doctors providing evidence-based emergency obstetric care. Task-sharing some obstetric responsibilities may help to reduce the mortality rates. This study was conducted to assess acceptability by the community and other healthcare providers, for task-sharing by community health workers (CHW) in the identification and initial care in hypertensive disorders in pregnancy. Methods This study was conducted in two districts of Karnataka state in south India. A total of 14 focus group discussions were convened with various community representatives: women of reproductive age (N = 6), male decision-makers (N = 2), female decision-makers (N = 3), and community leaders (N = 3). One-to-one interviews were held with medical officers (N = 2), private healthcare OBGYN specialists (N = 2), senior health administrators (N = 2), Taluka (county) health officers (N = 2), and obstetricians (N = 4). All data collection was facilitated by local researchers familiar with the setting and language. Data were subsequently transcribed, translated and analysed thematically using NVivo 10 software. Results There was strong community support for home visits by CHW to measure the blood pressure of pregnant women; however, respondents were concerned about their knowledge, training and effectiveness. The treatment with oral antihypertensive agents and magnesium sulphate in emergencies was accepted by community representatives but medical practitioners and health administrators had reservations, and insisted on emergency transport to a higher facility. The most important barriers for task-sharing were concerns regarding insufficient training, limited availability of medications, the questionable validity of blood pressure devices, and the ability of CHW to correctly diagnose and intervene in cases of hypertensive disorders of pregnancy. Conclusion Task-sharing to community-based health workers has potential to facilitate early diagnosis of the hypertensive disorders of pregnancy and assist in the provision of emergency care. We identified some facilitators and barriers for successful task-sharing of emergency obstetric care aimed at reducing mortality and morbidity due to hypertensive disorders of pregnancy.

Abstract Background The Lives Saved Tool (LiST) is a widely used resource for evidence-based decision-making regarding health program scale-up in low- and middle-income countries. LiST estimates the impact of specified changes in intervention coverage on mortality and stunting among children under 5 years of age. We aimed to improve the estimates of the parameters in LiST that determine the rate at which the effects of interventions to prevent stunting attenuate as children get older. Methods We identified datasets with serial measurements of children’s lengths or heights and used random effects models and restricted cubic splines to model the growth trajectories of children with at least six serial length/height measurements. We applied WHO growth standards to both measured and modelled (smoothed) lengths/heights to determine children’s stunting status at multiple ages (1, 6, 12, 24 months). We then calculated the odds ratios for the association of stunting at one age point with stunting at the next (“stunting-to-stunting ORs”) using both measured and smoothed data points. We ran analyses in LiST to compare the impact on intervention effect attenuation of using smoothed rather than measured stunting-to-stunting ORs. Results A total of 21,786 children with 178,786 length/height measurements between them contributed to our analysis. The odds of stunting at a given age were strongly related to whether a child is stunted at an earlier age, using both measured and smoothed lengths/heights, although the relationship was stronger for smoothed than measured lengths/heights. Using smoothed lengths/heights, we estimated that children stunted at 1 month have 45 times the odds of being stunted at 6 months, with corresponding odds ratios of 362 for the period 6 to 12 months and 175 for the period 12 to 24 months. Using the odds ratios derived from the smoothed data in LiST resulted in a somewhat slower attenuation of intervention effects over time, but substantial attenuation was still observed in the LiST outputs. For example, in Mali the effect of effectively eliminating SGA births reduced prevalence of stunting at age 59 months from 44.4% to 43.7% when using odds ratios derived from measured lengths/heights and from 44.4% to 41.9% when using odds ratios derived from smoothed lengths/heights. Conclusions Smoothing of children’s measured lengths/heights increased the strength of the association between stunting at a given age and stunting at an earlier age. Using odds ratios based on smoothed lengths/heights in LiST resulted in a small reduction in the attenuation of intervention effects with age and thus some increase in the estimated benefits, and may better reflect the true benefits of early nutritional interventions.

Abstract Background The health of mothers and their newborns is intricately related. The weight of the infant at birth is a powerful predictor of infant growth and survival, and is considered to be partly dependent on maternal health and nutrition during pregnancy. We conducted a longitudinal study in an urban community within Karachi to determine maternal predictors of newborn birth weight. Methods Four hundred pregnant women were enrolled in the study during the period 2011–2013. Data related to symptoms of acute respiratory illness (fever, cough, difficulty breathing, runny nose, sore throat, headache, chills, and myalgia/lethargy) in the pregnant women were collected weekly until delivery. Birth weight of the newborn was recorded within 14 days of delivery and the weight of

Background: The objective of this study was to document the worldwide decline of dracunculiasis (Guinea worm disease, GWD) burden, expressed as disability-adjusted life years (DALYs), from 1990 to 2016, as estimated in the Global Burden of Disease study 2016 (GBD 2016). While the annual number of cases of GWD have been consistently reported by WHO since the 1990s, the burden of disability due to GWD has not previously been quantified in GBD. Methods: The incidence of GWD was modeled for each endemic country using annual national case reports. A literature search was conducted to characterize the presentation of GWD, translate the clinical symptoms into health sequelae, and then assign an average duration to the infection. Prevalence measures by sequelae were multiplied by disability weights to estimate DALYs. Results: The total DALYs attributed to GWD across all endemic countries (n=21) in 1990 was 50,725 (95% UI: 35,265–69,197) and decreased to 0.9 (95% UI: 0.5–1.4) in 2016. A cumulative total of 12,900 DALYs were attributable to GWD from 1990 to 2016. Conclusions: Using 1990 estimates of burden propagated forward, this analysis suggests that between 990,000 to 1.9 million DALYs have been averted as a result of the eradication program over the past 27 years.

Objective To investigate the clinical characteristics of children who died from diarrhoea in low- and middle-income countries, such as the duration of diarrhoea, comorbid conditions, care-seeking behaviour and oral rehydration therapy use. Methods The study included verbal autopsy data on children who died from diarrhoea between 2000 and 2012 at seven sites in Bangladesh, Ethiopia, Ghana, India, Pakistan, Uganda and the United Republic of Tanzania, respectively. Data came from demographic surveillance sites, randomized trials and an extended Demographic and Health Survey. The type of diarrhoea was classified as acute watery, acute bloody or persistent and risk factors were identified. Deaths in children aged 1 to 11 months and 1 to 4 years were analysed separately. Findings The proportion of childhood deaths due to diarrhoea varied considerably across the seven sites from less than 3% to 30%. Among children aged 1–4 years, acute watery diarrhoea accounted for 31–69% of diarrhoeal deaths, acute bloody diarrhoea for 12–28%, and persistent diarrhoea for 12–56%. Among infants aged 1–11 months, persistent diarrhoea accounted for over 30% of diarrhoeal deaths in Ethiopia, India, Pakistan, Uganda and the United Republic of Tanzania. At most sites, more than 40% of children who died from persistent diarrhoea were malnourished. Conclusion Persistent diarrhoea remains an important cause of diarrhoeal death in young children in low- and middle-income countries. Research is needed on the public health burden of persistent diarrhoea and current treatment practices to understand why children are still dying from the condition.

Breast milk contains anti-rotavirus IgA antibodies and other innate immune factors that inhibit rotavirus replication in vitro. These factors could diminish the immunogenicity of oral rotavirus vaccines, particularly if breastfeeding occurs close to the time of vaccine administration.Between April 2011 and November 2012, we conducted an open label, randomized trial to compare the immunogenicity of Rotarix (RV1) in infants whose breastfeeding was withheld one hour before through one hour after vaccination with that in infants breastfed at the time of vaccination. The trial was conducted in the peri-urban area of Ibrahim Hyderi in Karachi, Pakistan. Both groups received three doses of RV1 at 6, 10 and 14 weeks of age. Seroconversion (anti-rotavirus IgA antibodies ≥ 20 U/mL in subjects seronegative at 6 weeks of age) following three vaccine doses (6, 10 and 14 weeks) was determined at 18 weeks of age (primary objective) and seroconversion following two doses (6 and 10 weeks) was determined at 14 weeks of age (secondary objective).Four hundred eligible infants were randomly assigned in a 1:1 ratio between the withholding breastfeeding and immediate breastfeeding arms. Overall, 353 (88.3%) infants completed the study according to protocol; 181 in the withholding breastfeeding group and 172 in the immediate breastfeeding group. After three RV1 doses, anti-rotavirus IgA antibody seroconversion was 28.2% (95% CI: 22.1; 35.1) in the withholding arm and 37.8% (95% CI: 30.9; 45.2) in the immediate breastfeeding arm (difference: -9.6% [95% CI: -19.2; 0.2] p = 0.07). After two doses of RV1, seroconversion was 16.6% (95% CI: 11.9; 22.7) in the withholding arm and 29.1% (95% CI: 22.8, 36.3) in the immediate breastfeeding arm (difference: -12.5% [95% CI: -21.2,-3.8] p = 0.005).Withholding breastfeeding around the time of RV1 vaccine administration did not lead to increased anti-rotavirus IgA seroconversion compared with that seen with a breastfeed at the time of vaccination. On the contrary, IgA seroconversion in infants immediately breastfed tended to be higher than in those withheld from a feeding. Our findings suggest that breastfeeding should be continued adlib around the time of rotavirus vaccination and withholding breastfeeding at that time is unlikely to improve the vaccine immunogenicity.ClinicalTrials.gov NCT01199874.

Background: The mitigation of unfair and avoidable differences in health is an increasing global priority. Observational studies including cohort, cross-sectional and case-control studies tend to report social determinants of health which could inform evidence syntheses on health equity and social justice. However, the extent of reporting and analysis of equity in equity-relevant observational studies is unknown. Methods: We define studies which report outcomes for populations at risk of experiencing inequities as “equity-relevant”. Using a random sampling technique we will identify 320 equity-relevant observational studies published between 1 January 2020 to 27 April 2022 by searching the MEDLINE database. We will stratify sampling by 1) studies in high-income countries (HIC) and low- and middle-income countries (LMIC) according to the World Bank classification, 2) studies focused on COVID and those which are not, 3) studies focused on populations at risk of experiencing inequities and those on general populations that stratify their analyses. We will use the PROGRESS framework which stands for place of residence, race or ethnicity, occupation, gender or sex, religion, education, socioeconomic status, social capital, to identify dimensions where inequities may exist. Using a previously developed data extraction form we will pilot-test on eligible studies and revise as applicable. Conclusions: The proposed methodological assessment of reporting will allow us to systematically understand the current reporting and analysis practices for health equity in observational studies. The findings of this study will help inform the development of the equity extension for the STROBE (Strengthening the Reporting of Observational studies in Epidemiology) reporting guidelines.