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Community health workers (CHWs) are a key part of the health workforce, with particular importance for reaching the most marginalised. CHWs' contributions during pandemics have received growing attention, including for COVID-19. This paper contributes to learning about CHWs' experiences during COVID-19, based on evidence from India, Bangladesh, Pakistan, Sierra Leone, Kenya and Ethiopia. The paper synthesises evidence from a set of research projects undertaken over 2020-2021. A thematic framework based on the research focus and related literature was used to code material from the reports. Following further analysis, interpretations were verified with the original research teams. CHWs made important contributions to the COVID-19 response, including in surveillance, community education, and support for people with COVID-19. There was some support for CHWs' work, including training, personal protective equipment and financial incentives. However, support varied between countries, cadres and individual CHWs, and there were significant gaps, leaving CHWs vulnerable to infection and stress. CHWs also faced a range of other challenges, including health system issues such as disrupted medical supply chains, insufficient staff and high workloads, a particular difficulty for female CHWs who were balancing domestic responsibilities. Their work was also affected by COVID-19 public health measures, such as restrictions on gatherings and travel; and by supply-side constraints related to community access and attitudes, including distrust and stigmatization of CHWs as infectious or informers. CHWs demonstrated commitment in adapting their work, for example ensuring patients had adequate drugs in advance of lockdowns, and using their own money and time to address increased transport costs and higher workloads. Effectiveness of these adaptations varied, and some involved coping in a context of inadequate support. CHW are critical for effective response to disease outbreaks, including pandemics like COVID-19. To support CHWs' contribution and protect their wellbeing, CHWs need adequate resources, managerial support, and motivation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Salve et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Discussions of health system resilience and emergency management often highlight the importance of coordination and partnership across government and with other stakeholders. However, both coordination and partnership have been identified as areas requiring further research. This paper identifies characteristics and enablers of effective coordination for emergency preparedness and response, drawing on experience from different countries with a range of shocks, including floods, drought, and COVID-19., Methods: The paper synthesises evidence from a set of reports related to research, evaluation and technical assistance projects, bringing together evidence from 11 countries in sub-Saharan Africa and South Asia. Methods for the original reports included primary data collection through interviews, focus groups and workshop discussions, analysis of secondary data, and document review. Reports were synthesised using a coding framework, and quality of evidence was considered for reliability of the findings., Results: The reports highlighted the role played by coordination and partnership in preparedness and response, and identified four key areas that characterise and enable effective coordination. First, coordination needs to be inclusive, bringing together different government sectors and levels, and stakeholders such as development agencies, universities, the private sector, local leaders and civil society, with equitable gender representation. Second, structural aspects of coordination bodies are important, including availability of coordination structures and regular meeting fora; clear roles, mandates and sufficient authority; the value of building on existing coordination mechanisms; and ongoing functioning of coordination bodies, before and after crises. Third, organisations responsible for coordination require sufficient capacity, including staff, funding, communication infrastructure and other resources, and learning from previous emergencies. Fourth, effective coordination is supported by high-level political leadership and incentives for collaboration. Country experience also highlighted interactions between these components, and with the wider health system and governance architecture, pointing to the need to consider coordination as part of a complex adaptive system., Conclusion: COVID-19 and other shocks have highlighted the importance of effective coordination and partnership across government and with other stakeholders. Using country experience, the paper identifies a set of recommendations to strengthen coordination for health system resilience and emergency management., (© 2022. The Author(s).)

Sepsis is a major global health problem, especially in sub-Saharan Africa. Improving patient care requires that healthcare providers understand patients' priorities and provide quality care within the confines of the context they work. We report the perspectives of patients, caregivers and healthcare workers regarding care quality for patients admitted for sepsis to public hospitals in Uganda and Malawi. This qualitative descriptive study in two hospitals included face-to face semi-structured interviews with purposively selected patients recovering from sepsis, their caregivers and healthcare workers. In both Malawi and Uganda, sepsis care often occurred in resource-constrained environments which undermined healthcare workers' capacity to deliver safe, consistent and accessible care. Constraints included limited space, strained; water, sanitation and hygiene (WASH) amenities and practices, inadequate human and material resources and inadequate provision for basic needs including nutrition. Heavy workloads for healthcare workers strained relationships, led to poor communication and reduced engagement with patients and caregivers. These consequences were exacerbated by understaffing which affected handover and continuity of care. All groups (healthcare workers, patients and caregivers) reported delays in care due to long queues and lack of compliance with procedures for triage, treatment, stabilization and monitoring due to a lack of expertise, supervision and context-specific sepsis management guidelines. Quality sepsis care relies on effective severity-based triaging, rapid treatment of emergencies and individualised testing to confirm diagnosis and monitoring. Hospitals in resource-constrained systems contend with limitations in key resources, including for space, staff, expertise, equipment and medicines, in turn contributing to gaps in areas such as WASH and effective care delivery, as well as communication and other relational aspects of care. These limitations are the predominant challenges to achieving high quality care., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Limbani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Left ventricular (LV) hypertrophy (LVH) in uncontrolled hypertension is an independent predictor of mortality, though its regression with treatment improves outcomes. Retrospective data suggest that early control of hypertension provides a prognostic advantage and this strategy is included in the 2018 European guidelines, which recommend treating grade II/III hypertension to target blood pressure (BP) within 3 months. The earliest LVH regression to date was demonstrated by echocardiography at 24 weeks. The effect of a rapid guideline-based treatment protocol on LV remodelling, with very early BP control by 18 weeks remains controversial and previously unreported. We aimed to determine whether such rapid hypertension treatment is associated with improvements in LV structure and function through paired cardiovascular magnetic resonance (CMR) scanning at baseline and 18 weeks, utilising CMR mass and feature tracking analysis., Methods: We recruited participants with never-treated grade II/III hypertension, initiating a guideline-based treatment protocol which aimed to achieve BP control within 18 weeks. CMR and feature tracking were used to assess myocardial morphology and function immediately before and after treatment., Results: We acquired complete pre- and 18-week post-treatment data for 41 participants. During the interval, LV mass index reduced significantly (43.5 ± 9.8 to 37.6 ± 8.3 g/m 2 , p < 0.001) following treatment, accompanied by reductions in LV ejection fraction (65.6 ± 6.8 to 63.4 ± 7.1%, p = 0.03), global radial strain (46.1 ± 9.7 to 39.1 ± 10.9, p < 0.001), mid-circumferential strain (- 20.8 ± 4.9 to - 19.1 ± 3.7, p = 0.02), apical circumferential strain (- 26.0 ± 5.3 to - 23.4 ± 4.2, p = 0.003) and apical rotation (9.8 ± 5.0 to 7.5 ± 4.5, p = 0.003)., Conclusions: LVH regresses following just 18 weeks of intensive antihypertensive treatment in subjects with newly-diagnosed grade II/III hypertension. This is accompanied by potentially advantageous functional changes within the myocardium and supports the hypothesis that rapid treatment of hypertension could improve clinical outcomes., Trial Registration: ISRCTN registry number: 57475376 (assigned 25/06/2015)., (© 2021. The Author(s).)

Background: Human infection studies (HIS) involve deliberately infecting healthy volunteers with a pathogen in a controlled environment to understand infection and support the development of effective vaccines or treatments. HIS research is expanding to many low and middle-income settings to accelerate vaccine development. Given the implementation of the first HIS research to establish the experimental human pneumococcal carriage model's feasibility, we sought to understand the participant's opinions and experiences. Methods: We used a qualitative, descriptive approach to understand participants perceptions and experiences on HIS participation. Sixteen healthy adult participants were invited to participate in in-depth exit interviews to discuss their experiences, motivations and concerns. Results: Our findings showed that the likelihood of participation in HIS research rests on three essential conditions: motivation to participate, compensation and advocacy. The motivation and decision to participate was based on reasons including altruism, patriotism, monetary and material incentives, and while compensation was deemed appropriate, concerns about unanticipated research-related risks were raised. Participant advocate groups were recommended for increasing awareness and educating others in the broader community about HIS research. Conclusions: Participants' experiences of HIS in Malawi provide the basis of what can be acceptable in HIS research in lower-income countries and areas where study procedures could be adjusted., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Mtunthama Toto N et al.)

Introduction: Cerebral small vessel disease (SVD) is prevalent in the elderly population and is associated with increased risk of dementia, stroke and disability. Currently there are no clear targets or strategies for the treatment of cerebral SVD. We set out to identify modifiable vascular treatment targets., Patients and Methods: 112 participants with and without a history of CVD underwent macrovascular, microvascular and endothelial function tests and an MRI head scan., Results: Increased carotid intima media thickness and carotid-femoral pulse wave velocity were associated with cerebral WMH (β=1·1 p=0·001 and β=1·66, p<0·0001 respectively). Adjusted cerebral resistance index (p=0·03) and brachial flow mediated dilation time to peak (p=0·001) were associated with the severity of cerebral WMH independent of age and sex. Post occlusive reactive hyperaemia time as a measure of microvascular reactivity was associated with WMH after adjustment for age and sex (p=0·03). Ankle Brachial Pressure Index and urinary albumin excretion rate predicted the severity of cerebral WMH (p=0·02 and 0·01 respectively). Age and hypertension were the most important risk factors for WMH severity (p< 0·0001)., Discussion: In addition to hypertension, microalbuminuria, arterial stiffness, vascular reactivity and cerebrovascular resistance could be potential treatment targets to halt the development or progression of cerebral SVD.

Background: Due to the importance of both prostaglandins (PGs) and leukotrienes (LTs) as pro-inflammatory mediators, and the potential for eicosanoid shunting in the presence of pathway target inhibitors, we have investigated an approach to inhibiting the formation of both PGs and LTs as part of a multi-targeted drug discovery effort., Methods: We generated ligand-protein X-ray crystal structures of known inhibitors of microsomal prostaglandin E2 synthase-1 (mPGES-1) and the 5-Lipoxygenase Activating Protein (FLAP), with their respective proteins, to understand the overlapping pharmacophores. We subsequently used molecular modeling and structure-based drug design (SBDD) to identify hybrid structures intended to inhibit both targets., Results: This work enabled the preparation of compounds 4 and 5, which showed potent in vitro inhibition of both targets., Significance: Our findings enhance the structural understanding of mPGES-1 and FLAP's unique ligand binding pockets and should accelerate the discovery of additional dual inhibitors for these two important integral membrane protein drug targets., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: There is growing interest in the collection, storage and reuse of biological samples for future research. Storage and future use of biological samples raise ethical concerns and questions about approaches that safeguard the interests of participants. The situation is further complicated in Africa where there is a general lack of governing ethical frameworks that could guide the research community on appropriate approaches for sample storage and use. Furthermore, there is limited empirical data to guide development of such frameworks. A qualitative study to address this gap was conducted with key stakeholders in Malawi to understand their experiences and perspectives regarding storage and usage of samples for future research., Methods: This study conducted 13 in-depth interviews with ethics committee members, regulators and researchers, and five focus group discussions with community representatives and clinical trial participants in Malawi. Interviews and focus group discussions were audio-recorded, transcribed verbatim, and thematically analysed., Results: On the current regulatory guidelines that governs the collection, storage and reuse of samples in Malawi, participants highlighted their different understanding of it, with some indicating that it prohibited the reuse and sharing of samples, while others believed it permitted. Views on the informed consent model used in Malawi, some stakeholders expressed that the current model limited options for sample contributors regarding future use. Researchers supported storing samples for future use in order to maximize their value and reduce research costs. However, they expressed concern over the exportation of samples highlighting that it could lead to misuse and would not support the development of research capacity within Malawi. They recommended use of broad consent or tiered consent and establishment of biobanks to address these concerns., Conclusions: Study findings highlighted the need for a review of the current regulatory guideline and the development of infrastructure to support the use of stored biological samples for future use among the research community in Malawi. At the moment, there are ethical and practical concerns arising from the collection, storage and secondary use of biological samples make it hard to reconcile scientific progress and the protection of participants.

Biometrics is the science of establishing the identity of an individual based on their physical attributes. Ethical concerns surrounding the appropriate use of biometrics have been raised, especially in resource-poor settings. A qualitative investigation was conducted to explore biometrics clients ( n  = 14), implementers ( n  = 12) and policy makers as well as bioethicists ( n  = 4) perceptions of the ethical aspects of implementing biometrics within the healthcare system in Malawi. Informed use, privacy and confidentiality as well as perceptions of benefits and harms were identified as major issues in the application of biometrics. Implementation of biometrics within the healthcare system in Malawi poses a range of potential ethical issues and practical challenges that impact on equitable uptake. There is a need for more research to explore the benefits and harms of biometrics in practice. Improved community engagement and sensitization should be a required component of biometrics introduction in Malawi., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)