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Comparative clinical and cost effectiveness of non-ST elevation myocardial infarction management strategies in patients living with kidney impairment during the COVID-19 pandemic: protocol for a target trial emulation using English routinely collected health data
Get PDFIntroduction:
Recent national and international guidelines recommend an invasive cardiac investigation and treatment strategy for people at high risk of cardiovascular events, regardless of kidney function status. These guidelines are based on observational evidence suggesting that the benefits of invasive cardiac investigation and treatment versus conservative management for non-ST elevated myocardial infarction (NSTEMI) outweigh the risks for people with kidney impairment. Despite this, among people with kidney impairment there is substantial variation in the proportions who have early invasive versus conservative NSTEMI management across hospitals in England. The impact of the COVID-19 pandemic on this variation is unknown. This protocol describes a study to investigate this variation and any changes during the COVID-19 pandemic, and how this variation will be used to evaluate the comparative clinical and cost-effectiveness of alternative NSTEMI treatment strategies among people with reduced kidney function.
Methods and analysis:
The CVD-COVID-UK/COVID-IMPACT British Heart Foundation (BHF) Data Science Centre Secure Data Environment, which contains nationally representative linked data on over 50 million people living in the United Kingdom, will be used to define a cohort of people hospitalised for NSTEMI. We will use linked secondary care data (Hospital Episode Statistics and National Institute for Cardiovascular Outcomes Research Audit) for cases with recent evidence of kidney impairment in primary care data (General Practice Extraction Service Data for pandemic planning and research) between 2019 and 2024. First, we will describe variation in early invasive versus conservative NSTEMI management at the hospital-level before and during the COVID-19 pandemic. Second, we will emulate a hypothetical trial using the target trial emulation framework to evaluate the comparative and cost-effectiveness of early invasive versus conservative NSTEMI management among people with reduced kidney function. We will use advanced analytical methods (clone-censor-weighting and instrumental variable analyses) to minimise the risk of bias due to immortal time and confounding by indication.
Ethics and dissemination:
This study was reviewed and approved by the BHF Data Science Centre Scientific and Public Panels. Results will be published in peer-reviewed journals, presented at conferences, and shared at patient and public panels. Analysis code will be shared in line with the BHF Data Science Centre’s code-sharing procedures
Causes of HIV-related CNS infection in Cameroon, Malawi, and Tanzania: epidemiological findings from the DREAMM HIV-related CNS implementation study.
Get PDFBACKGROUND: CNS infections cause approximately a third of HIV-related deaths. The Driving Reduced AIDS-Associated Meningo-encephalitis Mortality DREAMM study aimed to prospectively diagnose the aetiology of HIV-related CNS infection in five public hospitals in Cameroon, Malawi, and Tanzania. METHODS: DREAMM was a multicentre, hybrid type-2 implementation science project. Adults (aged ≥18 years) presenting with a first episode of suspected CNS infection, who were HIV seropositive or willing to have an HIV test, were eligible for recruitment. Following implementation of the DREAMM model of care, we measured the prevalence of cryptococcal meningitis, tuberculous meningitis, bacterial meningitis, and cerebral toxoplasmosis and did a χ2 test to assess whether prevalence differed between countries. We also reported disease-specific mortality and Toxoplasma gondii seroprevalence. FINDINGS: Of 356 participants with suspected CNS infection analysed at baseline, 269 (76%) were diagnosed as having a CNS infection. Of these, 202 (75%) had a confirmed diagnosis. Between Cameroon, Malawi, and Tanzania, the prevalence of the four main types of CNS infection differed (cryptococcal meningitis p=0·0014, bacterial meningitis p=0·0043, CNS tuberculosis p<0·0001, and toxoplasmosis p<0·0001). Cryptococcal meningitis (148 [55%] of 269) was the leading cause overall. The next most common causes were CNS tuberculosis in Tanzania (29 [29%] of 99) and bacterial meningitis in Malawi (15 [19%] of 80). In Cameroon, cerebral toxoplasmosis (39 [43%] of 90) was the leading cause followed by cryptococcal meningitis (36 [40%] of 90). For cryptococcal meningitis, all-cause 2-week mortality was 23% (34 of 147) and all-cause 10-week mortality was 45% (66 of 146). INTERPRETATION: Within the study population, the aetiology of HIV-related CNS infection varied substantially between Malawi, Cameroon, and Tanzania. Additional prospective epidemiological data are needed to inform HIV programmes. 2-week cryptococcal meningitis mortality outcomes were similar to those of clinical trials. However, new interventions are urgently needed to sustain mortality reductions following hospital discharge. FUNDING: European and Developing Countries Clinical Trials Partnership and French Agency for Research on AIDS and Viral Hepatitis. TRANSLATIONS: For the French and Portuguese translations of the abstract see Supplementary Materials section
School Meals Case Study: Guatemala [Estudio de caso sobre alimentación escolar: Guatemala].
Get PDFEste estudio de caso sobre los programas de alimentación escolar forma parte de una colección liderada por la Comunidad de Práctica "Buenos Ejemplos" del Consorcio de Investigación para la Salud y la Nutrición Escolar. El estudio de caso sobre la alimentación escolar en Guatemala tiene como propósito documentar la organización, financiamiento y monitoreo del programa nacional de alimentación escolar en todo el país. Los objetivos de este estudio de caso incluyen presentar una introducción al perfil del país, describir el diseño e implementación de los programas de alimentación escolar, detallar sus procesos de monitoreo y evaluación, y resaltar lecciones aprendidas, buenas prácticas y desafíos. Este estudio de caso se presenta como un documento de trabajo y puede actualizarse para reflejar cambios y circunstancias en evolución. La Comunidad de Práctica "Buenos Ejemplos" apoya la generación de evidencia dentro del Consorcio de Investigación para la Salud y la Nutrición Escolar, que es el brazo de generación de evidencia de la Coalición para la Alimentación Escolar. El objetivo del Consorcio de Investigación es llevar a cabo estudios independientes en diversos sectores y generar evidencia sólida, convincente y aplicable sobre los beneficios de los programas de alimentación escolar, con el fin de respaldar la toma de decisiones basada en evidencia en políticas y prácticas de salud y nutrición escolar.
This school meals case study forms part of a collection led by the Research Consortium for School Health and Nutrition’s "Good Examples" Community of Practice. The School Meals Case Study of Guatemala serves to document how the national school meals programme is organized, funded, and monitored throughout the country. The objectives of this case study include presenting an introduction to the country profile, outlining the design and implementation of school feeding programmes, describing their monitoring and evaluation processes, and highlighting lessons learned, best practices, and challenges. This case study is written as a working paper, and can be updated to reflect evolving circumstances. The ‘Good Examples’ Community of Practice supports the evidence generation of the Research Consortium for School Health and Nutrition, the evidence-generating arm of the School Meals Coalition. The Research Consortium’s objective is to carry out independent research across diverse sectors and generate solid, compelling, and actionable evidence regarding the benefits of school food programs to inform evidence-based decision-making on school health and nutrition policies and practices
Pharmacokinetics, Safety and Antiviral Activity of Rilpivirine in Antiretroviral-naïve Children With HIV ≥6 to <12 Years Old: Week 48 and Final Analysis of Cohort 2 From the Open-label, Phase 2 PAINT Study.
Get PDFBACKGROUND: Rilpivirine has shown adequate antiviral activity, consistent pharmacokinetics and safety in adults and adolescents living with HIV-1. Pharmacokinetics, safety, and antiviral activity of rilpivirine were assessed in children, following at least 48 weeks of treatment. METHODS: Cohort 2 of the open-label, phase 2 PAINT study (NCT00799864) included antiretroviral-naïve children living with HIV-1 ≥6 to 95%) to the treatment. Pharmacokinetic exposures were similar across the recommended weight-based doses and within a range comparable to exposures seen in adult studies. At week 48, 13/18 (72%) children achieved virologic response (HIV-1 RNA <50 copies/mL, FDA Snapshot). The mean (SE) increase from baseline to week 48 in CD4+ count was 213.4 (77.80) cells/μL. Overall postbaseline, 2 participants experienced virologic failure, of which 1 carried treatment-emergent rilpivirine resistance-associated mutations (RAMs); 3 of 5 participants with suspected virologic failure carried rilpivirine and NRTI RAMs. No new safety signals were identified in this population. CONCLUSIONS: At week 48, rilpivirine achieved adequate viral suppression in antiretroviral-naïve children ≥6 to <12 years of age. The pharmacokinetic, safety and virologic profile of rilpivirine in this age group was consistent with observations in adults and adolescents living with HIV-1
A roadmap of priority evidence gaps for the co-implementation of malaria vaccines and perennial malaria chemoprevention.
Get PDFProgress in malaria control will rely on deployment and effective targeting of combinations of interventions, including malaria vaccines and perennial malaria chemoprevention (PMC). Several countries with PMC programmes have introduced malaria vaccination into their essential programmes on immunizations, but empirical evidence on the impact of combining these two interventions and how best to co-implement them are lacking. At the American Society of Tropical Medicine and Hygiene 2023 annual meeting, a stakeholder meeting was convened to identify key policy, operational and research gaps for co-implementation of malaria vaccines and PMC. Participants from 11 endemic countries, including representatives from national malaria and immunization programmes, the World Health Organization, researchers, implementing organizations and funders attended. Identified evidence gaps were prioritized to select urgent issues to inform co-implementation. The output of these activities is a strategic roadmap of priority malaria vaccine and PMC co-implementation evidence gaps, and solutions to address them. The roadmap was presented to stakeholders for feedback at the 2024 Multilateral Initiative on Malaria meeting and revised accordingly. The roadmap outlines four key areas of work to address urgent evidence gaps for co-implementation: (1) support to the global and national policy process, (2) implementation support and research, (3) clinical studies, and (4) modelling. Together, these areas will provide practical guidance on the co-implementation of the interventions, and robust evidence to inform decision-making on how best to design, optimize and scale-up co-implementation in different contexts, including if and in what contexts the co-implementation is cost-effective, and the optimal schedule for co-implementation. This will work towards supporting the policy process on co-implementation of malaria vaccines and PMC, and achieving the most impactful use of available resources for the prevention of malaria in children.
Note: This output has been corrected, please see the publisher’s website: https://malariajournal.biomedcentral.com/articles/10.1186/s12936-025-05410-
Open science policy guidelines promoting open data sharing in low and middle-income countries for respiratory health research under NIHR Global RESPIRE project.
Get PDFOpen science drives progress, especially in the low-and-middle-income countries (LMICs), where data security and confidentiality are at risk due to lack of resources and non-compliance with diverse privacy laws. The National Institutes of Health and Care Research (NIHR) Global Health Research Unit on Respiratory Health (RESPIRE 2) project, funded by the UK NIHR, is a global collaboration led by the University of Edinburgh and Universiti Malaya, in partnership with seven LMICs and the UK. The collaboration developed open science policy guidelines to streamline data sharing, while ensuring compliance with privacy laws. They thus enable open data sharing in RESPIRE, furthering knowledge and scientific progress and providing greater research opportunities. This is in alignment with UNESCO, which promotes the open science movement to make scientific research and data more accessible, transparent, and collaborative. Some of the key components of this policy guideline are: Here we outline some of the key components of this policy guideline and provide recommendations. By following ethical data-sharing practices and fostering international collaboration, researchers, research assistants, technicians, and research support services can improve the impact of their research and contribute significantly to resolving global health challenges. Policymakers, research institutions, and funding agencies must support the adoption of open science practices in local contexts for long-term sustainability
Uncertainty quantification in cost-effectiveness analysis for stochastic-based infectious disease models: Insights from surveillance on lymphatic filariasis.
Get PDFCost-effectiveness analyses (CEA) typically involve comparing the effectiveness and costs of one or more interventions compared to the standard of care, in order to determine which intervention should be optimally implemented to maximise population health within the constraints of the healthcare budget. Traditionally, cost-effectiveness evaluations are expressed using incremental cost-effectiveness ratios (ICERs), which are compared with a fixed willingness-to-pay (WTP) threshold. Due to the inherent uncertainty in intervention costs and the overall burden of disease, particularly with regard to diseases in populations that are difficult to study, it becomes important to consider uncertainty quantification while estimating ICERs. To tackle the challenges of uncertainty quantification in CEA, we propose an alternative paradigm utilizing the Linear Wasserstein framework combined with Linear Discriminant Analysis (LDA) using a demonstrative example of lymphatic filariasis (LF). This approach uses geometric embeddings of the overall costs for treatment and surveillance, disability-adjusted life-years (DALYs) averted for morbidity by quantifying the burden of disease due to the years lived with disability, and probabilities of local elimination over a time-horizon of 20 years to evaluate the cost-effectiveness of lowering the stopping thresholds for post-surveillance determination of LF elimination as a public health problem. Our findings suggest that reducing the stopping threshold from <1 % to <0.5 % microfilaria (mf) prevalence for adults aged 20 years and above, under various treatment coverages and baseline prevalences, is cost-effective. When validated on 20 % of test data, for 65 % treatment coverage, a government expenditure of WTP ranging from 3000 per 1 % increase in local elimination probability justifies the switch to the lower threshold as cost-effective. Stochastic model simulations often lead to parameter and structural uncertainty in CEA. Uncertainty may impact the decisions taken, and this study underscores the necessity of better uncertainty quantification techniques within CEA for making informed decisions
Making sense of the unexpected: neural tube defects in Ethiopia
Get PDFNeural tube defects are severe birth defects with visible and devastating malformations in babies, and can lead to death before, during or soon after birth. Neural tube defects are preventable, and in many countries there has been an increasing ‘responsibilization’ of pregnant women in terms of taking folic acid before and during pregnancy to avoid these malformations in their babies. In low-income countries, many women are not in positions to plan pregnancies, access appropriate information and allocate scarce resources to avoid neural tube defects. Lack of compliance with biomedical management strategies remains a challenge in many places, and, in this paper, we turn the attention to local perspectives on neural tube defects in eastern Ethiopia, where there are high number of cases. Drawing on interviews and focus group discussions with mothers, community members, health workers and traditional birth attendants, we explore why the malformations of babies lead to stigma of their families and demonstrate how local forms of responsibilization impact the families of the babies born with neural tube defects
Perceptions and knowledge of diabetes in poor urban communities in Accra, Ghana.
Get PDFDiabetes is a major public health concern, leading to costly and life-threating complications while significantly impacting quality of life. However, limited evidence exists on how diabetes is understood in poor urban communities in Africa, including Ghana. Evidence suggests that community beliefs about disease can shape health outcomes and influence intervention strategies. This cross-sectional qualitative study assessed perceptions and knowledge of diabetes in two poor urban communities in Accra, Ghana. Thirteen focus group discussions were conducted, involving ninety-four participants segmented by sex, age, and diabetes status. Participants frequently cited unhealthy diets, alcohol consumption, and smoking as primary causes of diabetes. Knowledge of prevention was primarily focused on maintaining a healthy diet and engaging in physical activity. Managing diabetes was associated with adopting healthy lifestyles and seeking care at a health facility. Additionally, covert diabetes-related stigma was observed in the communities, with implications for illness disclosure and overall quality of life. Community-wide interventions are needed to increase awareness on the causes and consequences of diabetes, address negative social norms, and expand screening programmes to facilitate early detection and guidance for effective disease management
Born Too Soon: Care for small and sick newborns, evidence for investment and implementation.
Get PDFPROGRESS: Over the past decade, the world has made policy progress for newborns including the first global Sustainable Development Goal (SDG) target 3.2 (< 12 neonatal deaths per 1000 live births) and the Every Newborn Action Plan (ENAP). However, gaps remain for investment and action, especially for babies born too soon, too small, or who become sick. An estimated 20-30 million newborns have life-threatening conditions requiring hospital care each year. Annually, approximately 2.3 million newborns die during the neonatal period, the majority being preterm. A further 1 million newborn survivors are estimated to have long-term disabilities. PROGRAMMATIC PRIORITIES: To achieve SDG 3.2 by 2030, we need to accelerate four-fold. The shift to 80% of births in health facilities creates opportunities for impact, for both maternal and newborn care. Increased coverage and quality of high-impact newborn interventions is urgently needed to reach SDG targets. Most neonatal deaths and disabilities are preventable through an evidence-based package for small and sick newborn care (SSNC), with greatest impact seen in preterm babies-particularly through respiratory support and kangaroo mother care-while placing families at the centre of care. SSNC scale-up requires addressing ten core components, defined by WHO/UNICEF, based on a health systems approach: political commitment and leadership; financing; human resources; appropriate infrastructure; equipment and commodities; robust data systems and use of data for action; referral systems; linkage with high-quality maternal care; family and community involvement; and post-discharge follow-up. Specific focus is required for fragile conflict settings, accounting for 25% global births but 39% global newborn deaths. PIVOTS: More ambitious investment in high-quality, family-centred care for vulnerable newborns can give a high return of between US 1 invested. Accelerating implementation requires diverse stakeholders, including political leaders, bureaucratic and technical leadership in country, professional societies, civil society, the private sector and importantly from families and communities. Cross-country collaboration and strengthening capacities of low- and middle-income countries to address gaps in newborn care are essential for innovations to reach high-burden, conflict-affected, and marginalised populations. Integrating newborn care follow-up into wider child and family care systems is crucial to ensure newborns not only survive but also thrive