Informing prevention of stillbirth and preterm birth in Malawi:development of a minimum dataset for health facilities participating in the DIPLOMATIC collaboration

OBJECTIVE: The global research group, DIPLOMATIC (Using eviDence, Implementation science, and a clinical trial PLatform to Optimise MATernal and newborn health in low Income Countries), aims to reduce stillbirths and preterm births and optimise outcomes for babies born preterm. Minimum datasets for routine data collection in healthcare facilities participating in DIPLOMATIC (initially in Malawi) were designed to assist understanding of baseline maternal and neonatal care processes and outcomes, and facilitate evaluation of improvement interventions and pragmatic clinical trials. DESIGN: Published and grey literature was reviewed alongside extensive in-country consultation to define relevant clinical best practice guidance, and the existing local data and reporting infrastructure, to identify requirements for the minimum datasets. Data elements were subjected to iterative rounds of consultation with topic experts in Malawi and Scotland, the relevant Malawian professional bodies and the Ministry of Health in Malawi to ensure relevance, validity and feasibility. SETTING: Antenatal, maternity and specialist neonatal care in Malawi. RESULTS: The resulting three minimum datasets cover the maternal and neonatal healthcare journey for antenatal, maternity and specialist neonatal care, with provision for effective linkage of records for mother/baby pairs. They can facilitate consistent, precise recording of relevant outcomes (stillbirths, preterm births, neonatal deaths), risk factors and key care processes. CONCLUSIONS: Poor quality routine data on care processes and outcomes constrain healthcare system improvement. The datasets developed for implementation in DIPLOMATIC partner facilities reflect, and hence support delivery of, internationally agreed best practice for maternal and newborn care in low-income settings. Informed by extensive consultation, they are designed to integrate with existing local data infrastructure and reporting as well as meeting research data needs. This work provides a transferable example of strengthening data infrastructure to underpin a learning healthcare system approach in low-income settings.DIPLOMATIC is funded by the UK National Institute for Health Research

The Lancet Commission on peaceful societies through health equity and gender equality

The multiple and overlapping crises faced by countries, regions, and the world appear unprecedented in their magnitude and complexity. Protracted conflicts continue and new ones emerge, fuelled by geopolitics and social, political, and economic pressures. The legacy of the COVID-19 pandemic, economic uncertainty, climatic events ranging from droughts to fires to cyclones, and rising food insecurity add to these pressures. These crises have exposed the inadequacy of national and global leadership and governance structures. The world is experiencing a polycrisis—ie, an interaction of multiple crises that dramatically intensifies suffering, harm, and turmoil, and overwhelms societies' ability to develop effective policy responses. Bold approaches are needed to enable communities and countries to transition out of harmful cycles of inequity and violence into beneficial cycles of equity and peace. The Lancet Commission on peaceful societies through health equity and gender equality provides such an approach. The Commission, which had its inaugural meeting in May, 2019, examines the interlinkages between Sustainable Development Goal 3 (SDG3) on health; SDG5 on gender equality; and SDG16 on peace, justice, and strong institutions. Our research suggests that improvements to health equity and gender equality are transformative, placing societies on pathways towards peace and wellbeing. Four key messages emerge from our research. First, health equity and gender equality have a unique and powerful ability to contribute to more peaceful societies. This Commission recognises the complex web of factors that contribute to conflict. Moreover, health equity and gender equality are themselves shaped by social and economic processes that are complex, contextually specific, and unfold over long timescales. Even accounting for this complexity, our Commission provides evidence that improvements in health equity and gender equality can place societies on pathways to peace. Health equity and gender equality are powerful agents of transformation because they require definitive actions, namely tangible and sustained policies that improve health and gender equality outcomes. We refer to these definitive actions as the mechanisms of health equity and gender equality. Health equity requires countries to embrace the right to health, acknowledge disparities, and recognise that universal access to health-care services is crucial for human potential and dignity. Gender equality requires laws to protect the rights of women and sexual and gender minorities. All individuals need equal access to education, resources, technology, infrastructure, and safety and security to enable participation in the economy, civil society, and politics. Processes to advance health equity and gender equality are more powerful when they operate together, through access to comprehensive sexual and reproductive health services. Advocacy is also an essential component as it builds a social consensus that the principles of health equity and gender equality apply to all individuals, regardless of their gender or other forms of identity. These tangible actions or mechanisms transform capabilities, a term that we define here as what people are able to do and to be. With improved health equity and gender equality, individuals can access economic resources and assets, live in safety and security, and exercise greater agency. Through these changes, human capital improves and economic growth becomes more inclusive. Social capital is strengthened and social norms are altered to inhibit violence and aggression. Although political processes are characterised by short-term dynamics, the institutionalisation of gender equality and health equity improves the quality of governance and can strengthen the social contract between the government and the citizenry. These processes interact with each other in self-reinforcing feedback loops creating beneficial cycles that influence the dynamics of economic, social, and political systems. For countries locked in harmful cycles of inequity, conflict, and instability, our research suggests that improvements in gender equality and health equity help nudge them onto pathways towards peace. Second, to deliver the promise of the Commission's research, health equity and gender equality principles and processes must be led by communities and tailored to their context. Local and national actors must drive improvements in health equity and gender equality, a process we refer to as change from the inside out. Although communities benefit from evidence from other contexts, we highlight the danger of importing policy models from other contexts. Health and gender systems are social systems, deeply intertwined in culture, contexts, and politics. Tangible and sustained improvements require gender equality and health equity mechanisms to be led by national actors, rooted in the local context, shaped by data, sustained through national systems, and accountable to communities. Efforts to improve gender equality are always contentious, but are transformative, enabling the recognition of the equal rights of women, girls, and sexual and gender minorities within the private and public spheres. Our Commission supports the call from decolonisation advocates for structural reform of global development processes to enable locally driven, context-specific change. However, we also stress that these local and national efforts should leverage and build upon the global scaffolding or architecture of norms, initiatives, funding, and institutions designed to advance health equity and gender equality. Third, within the health sector and beyond, the Commission calls on policy makers to embrace, advocate for, and advance health equity and gender equality. In the health sector, services and systems must adopt, implement, and be accountable to benchmarks for gender equal health responses. The health sector is a key social, economic, and political institution. Individuals engage with health services throughout their lifespan. Health professionals are respected leaders within their communities. Given their reproductive and caregiving roles, women are a majority of users as well as providers of health care. Yet health services and systems can reflect and reinforce implicit biases that undermine access to and delivery of services and the effectiveness of health policy decisions. The gender-blind response to the COVID-19 pandemic and the tolerance of sexual exploitation within humanitarian contexts are examples of the failure to integrate gender equality principles within health sector strategies and responses. Our Commission provides definitive benchmarks for gender equal health services and humanitarian action. If policy makers advance these benchmarks, health outcomes as well as the level of gender equality would improve. Finally, given the evidence we present in this Commission, health equity and gender equality must form an integral part of national and global processes to promote peace and wellbeing. The beneficial cycles of health equity and gender equality unfold over long time scales. Conflict management and humanitarian efforts understandably prioritise short-term interventions to reduce human suffering and stop violence. However, given the path dependencies established by such engagement, gender equality and health equity must be built into these short-term interventions. When integrating health equity and gender equality into humanitarian and conflict management interventions, we need to better analyse conflict dynamics and understand what conditions foster backlash, including when and how best to confront, counter, navigate, and minimise backlash. Gender equality and health equity processes must also recognise how gender norms impact men and boys, and not assume women and girls have the power to single-handedly transform their environments. Policy processes from the UN Sustainable Development Goals to the Group of Seven and Group of 20 Agendas present an important opportunity to advance this agenda. Although global initiatives can provide financial and technical support, gender or health outcomes cannot be instrumentalised or pursued for the interests of external actors rather than for the benefit of communities. The Lancet Commission provides an agenda for a path forward, rooted in a vision of our shared human dignity and collective responsibility to build a more equitable world. This agenda takes communities, governments, and international agencies on a challenging and sometimes contentious journey forward. We can accept the challenge and leverage this moment of opportunity to advance this agenda, or our politics and policies can entrench inequities and create the conditions for a more conflictual world. The choice is ours.The Swedish MFA, the Ministry of Social Affairs and Health in Finland, Canada's International Development Research Centre, and a donor whose organisation's policy is to remain anonymous but is known to The Lancet.https://www.thelancet.com/journals/lanhiv/home2024-05-04hj2024EconomicsSDG-03:Good heatlh and well-beingSDG-05:Gender equalitySDG-16:Peace,justice and strong institution

Distinct clinical and immunological profiles of patients with evidence of SARS-CoV-2 infection in sub-Saharan Africa

Although the COVID-19 pandemic has left no country untouched there has been limited research to understand clinical and immunological responses in African populations. Here we characterise patients hospitalised with suspected (PCR-negative/IgG-positive) or confirmed (PCR-positive) COVID-19, and healthy community controls (PCR-negative/IgG-negative). PCR-positive COVID-19 participants were more likely to receive dexamethasone and a beta-lactam antibiotic, and survive to hospital discharge than PCR-negative/IgG-positive and PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants exhibited a nasal and systemic cytokine signature analogous to PCR-positive COVID-19 participants, predominated by chemokines and neutrophils and distinct from PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants had increased propensity for Staphylococcus aureus and Streptococcus pneumoniae colonisation. PCR-negative/IgG-positive individuals with high COVID-19 clinical suspicion had inflammatory profiles analogous to PCR-confirmed disease and potentially represent a target population for COVID-19 treatment strategies

Stimulating a Canadian narrative for climate

ABSTRACT: This perspective documents current thinking around climate actions in Canada by synthesizing scholarly proposals made by Sustainable Canada Dialogues (SCD), an informal network of scholars from all 10 provinces, and by reviewing responses from civil society representatives to the scholars' proposals. Motivated by Canada's recent history of repeatedly missing its emissions reduction targets and failing to produce a coherent plan to address climate change, SCD mobilized more than 60 scholars to identify possible pathways towards a low-carbon economy and sustainable society and invited civil society to comment on the proposed solutions. This perspective illustrates a range of Canadian ideas coming from many sectors of society and a wealth of existing inspiring initiatives. Solutions discussed include climate change governance, low-carbon transition, energy production, and consumption. This process of knowledge synthesis/creation is novel and important because it provides a working model for making connections across academic fields as well as between academia and civil society. The process produces a holistic set of insights and recommendations for climate change actions and a unique model of engagement. The different voices reported here enrich the scope of possible solutions, showing that Canada is brimming with ideas, possibilities, and the will to act

Cohort Profile: Burden of Obstructive Lung Disease (BOLD) study

The Burden of Obstructive Lung Disease (BOLD) study was established to assess the prevalence of chronic airflow obstruction, a key characteristic of chronic obstructive pulmonary disease, and its risk factors in adults (≥40 years) from general populations across the world. The baseline study was conducted between 2003 and 2016, in 41 sites across Africa, Asia, Europe, North America, the Caribbean and Oceania, and collected high-quality pre- and post-bronchodilator spirometry from 28 828 participants. The follow-up study was conducted between 2019 and 2021, in 18 sites across Africa, Asia, Europe and the Caribbean. At baseline, there were in these sites 12 502 participants with high-quality spirometry. A total of 6452 were followed up, with 5936 completing the study core questionnaire. Of these, 4044 also provided high-quality pre- and post-bronchodilator spirometry. On both occasions, the core questionnaire covered information on respiratory symptoms, doctor diagnoses, health care use, medication use and ealth status, as well as potential risk factors. Information on occupation, environmental exposures and diet was also collected

Youth participation in the fight against AIDS in South Africa: from policy to practice

Effective youth participation in social development and civic life can enhance young peoples' health and well-being. Yet many obstacles stand in the way of such involvement. Drawing on 105 interviews, 52 focus groups and fieldworker diaries, this paper reports on a study of a rural South African project which sought to promote effective youth participation in HIV/AIDS management. The paper highlights three major obstacles which might be tackled more explicitly in future projects: (i) reluctance by community adults to recognise the potential value of youth inputs, and an unwillingness to regard youth as equals in project structures; (ii) lack of support for meaningful youth participation by external health and welfare agencies involved in the project; and (iii) the failure of the project to provide meaningful incentives to encourage youth involvement. The paper highlights five psycho-social preconditions for participation in AIDS projects (knowledge, social spaces for critical thinking, a sense of ownership, confidence and appropriate bridging relationships). We believe this framework provides a useful and generalisable way of conceptualising the preconditions for effective 'participatory competence' in youth projects beyond the specialist HIV/AIDS arena

Preprint: A drug repurposing screen for whipworms informed by comparative genomics

Hundreds of millions of people worldwide are infected with the whipworm Trichuris trichiura. Novel treatments are urgently needed as current drugs, such as albendazole, have relatively low efficacy. We have investigated whether drugs approved for other human diseases could be repurposed as novel anti-whipworm drugs. In a previous comparative genomics analysis, we identified 409 drugs approved for human use that we predicted to target parasitic worm proteins. Here we tested these ex vivo by assessing motility of adult worms of Trichuris muris, the murine whipworm, an established model for human whipworm research. We identified 14 compounds with EC50 values of ≤50 μM against T. muris ex vivo, and selected nine for testing in vivo. However, the best worm burden reduction seen in mice was just 19%. The high number of ex vivo hits against T. muris shows that we were successful at predicting parasite proteins that could be targeted by approved drugs. In contrast, the low efficacy of these compounds in mice suggest challenges due to their chemical properties (e.g. lipophilicity, polarity, molecular weight) and pharmacokinetics (e.g. absorption, distribution, metabolism, and excretion) that may (i) promote absorption by the host gastrointestinal tract, thereby reducing availability to the worms embedded in the large intestine, and/or (ii) restrict drug uptake by the worms. This indicates that identifying structural analogues that have reduced absorption by the host, and increased uptake by worms, may be necessary for successful drug repurposing against whipworms. Therefore, we recommend that prior to in vivo studies, future researchers first assess drug absorption by the host, for example, using human intestinal organoids or cell lines, and drug uptake by whipworms using intestinal organoids infected with T. muris

A drug repurposing screen for whipworms informed by comparative genomics.

Hundreds of millions of people worldwide are infected with the whipworm Trichuris trichiura. Novel treatments are urgently needed as current drugs, such as albendazole, have relatively low efficacy. We have investigated whether drugs approved for other human diseases could be repurposed as novel anti-whipworm drugs. In a previous comparative genomics analysis, we identified 409 drugs approved for human use that we predicted to target parasitic worm proteins. Here we tested these ex vivo by assessing motility of adult worms of Trichuris muris, the murine whipworm, an established model for human whipworm research. We identified 14 compounds with EC50 values of ≤50 μM against T. muris ex vivo, and selected nine for testing in vivo. However, the best worm burden reduction seen in mice was just 19%. The high number of ex vivo hits against T. muris shows that we were successful at predicting parasite proteins that could be targeted by approved drugs. In contrast, the low efficacy of these compounds in mice suggest challenges due to their chemical properties (e.g. lipophilicity, polarity, molecular weight) and pharmacokinetics (e.g. absorption, distribution, metabolism, and excretion) that may (i) promote absorption by the host gastrointestinal tract, thereby reducing availability to the worms embedded in the large intestine, and/or (ii) restrict drug uptake by the worms. This indicates that identifying structural analogues that have reduced absorption by the host, and increased uptake by worms, may be necessary for successful drug development against whipworms