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Women, children and adolescents (WCA), especially in low-income and middle-income countries (LMICs), will bear the worst consequences of climate change during their lifetimes, despite contributing the least to global greenhouse gas emissions. Investing in WCA can address these inequities in climate risk, as well as generating large health, economic, social and environmental gains. However, women’s, children’s and adolescents’ health (WCAH) is currently not mainstreamed in climate policies and financing. There is also a need to consider new and innovative financing arrangements that support WCAH alongside climate goals.

We provide an overview of the threats climate change represents for WCA, including the most vulnerable communities, and where health and climate investments should focus. We draw on evidence to explore the opportunities and challenges for health financing, climate finance and co-financing schemes to enhance equity and protect WCAH while supporting climate goals.

WCA face threats from the rising burden of ill-health and healthcare demand, coupled with constraints to healthcare provision, impacting access to essential WCAH services and rising out-of-pocket payments for healthcare. Climate change also impacts on the economic context and livelihoods of WCA, increasing the risk of displacement and migration. These impacts require additional resources to support WCAH service delivery, to ensure continuity of care and protect households from the costs of care and enhance resilience. We identify a range of financing solutions, including leveraging climate finance for WCAH, adaptive social protection for health and adaptations to purchasing to promote climate action and support WCAH care needs.

Nat Microbiol. 2024 Apr 26. doi: 10.1038/s41564-024-01683-0. Online ahead of print.

NO ABSTRACT

PMID:38671272 | DOI:10.1038/s41564-024-01683-0

Respir Res. 2024 Apr 25;25(1):180. doi: 10.1186/s12931-024-02800-7.

ABSTRACT

BACKGROUND: Pulmonary ionocytes have been identified in the airway epithelium as a small population of ion transporting cells expressing high levels of CFTR (cystic fibrosis transmembrane conductance regulator), the gene mutated in cystic fibrosis. By providing an infinite source of airway epithelial cells (AECs), the use of human induced pluripotent stem cells (hiPSCs) could overcome some challenges of studying ionocytes. However, the production of AEC epithelia containing ionocytes from hiPSCs has proven difficult. Here, we present a platform to produce hiPSC-derived AECs (hiPSC-AECs) including ionocytes and investigate their role in the airway epithelium.

METHODS: hiPSCs were differentiated into lung progenitors, which were expanded as 3D organoids and matured by air-liquid interface culture as polarised hiPSC-AEC epithelia. Using CRISPR/Cas9 technology, we generated a hiPSCs knockout (KO) for FOXI1, a transcription factor that is essential for ionocyte specification. Differences between FOXI1 KO hiPSC-AECs and their wild-type (WT) isogenic controls were investigated by assessing gene and protein expression, epithelial composition, cilia coverage and motility, pH and transepithelial barrier properties.

RESULTS: Mature hiPSC-AEC epithelia contained basal cells, secretory cells, ciliated cells with motile cilia, pulmonary neuroendocrine cells (PNECs) and ionocytes. There was no difference between FOXI1 WT and KO hiPSCs in terms of their capacity to differentiate into airway progenitors. However, FOXI1 KO led to mature hiPSC-AEC epithelia without ionocytes with reduced capacity to produce ciliated cells.

CONCLUSION: Our results suggest that ionocytes could have role beyond transepithelial ion transport by regulating epithelial properties and homeostasis in the airway epithelium.

PMID:38664797 | DOI:10.1186/s12931-024-02800-7

Information systems for community health have become increasingly sophisticated and evidence-based in the last decade and they are now the most widely used health information systems in many low-income and middle-income countries. This study aimed to establish consensus regarding key features and interoperability priorities for community health information systems (CHISs).

A Delphi study was conducted among a systematically selected panel of CHIS experts. This impressive pool of experts represented a range of leading global health institutions, with gender and regional balance as well as diversity in their areas of expertise. Through five rounds of iterative surveys and follow-up interviews, the experts established a high degree of consensus. We supplemented the Delphi study findings with a series of focus group discussions with 10 community health worker (CHW) leaders.

CHISs today are expected to adapt to a wide range of local contextual requirements and to support and improve care delivery. While once associated with a single role type (CHWs), these systems are now expected to engage other end users, including patients, supervisors, clinicians and data managers. Of 30 WHO-classified digital health interventions for care providers, experts identified 23 (77%) as being important for CHISs. Case management and care coordination features accounted for more than one-third (14 of 37, 38%) of the core features expected of CHISs today, a higher proportion than any other category. The highest priority use cases for interoperability include CHIS to health management information system monthly reporting and CHIS to electronic medical record referrals.

CHISs today are expected to be feature-rich, to support a range of user roles in community health systems, and to be highly adaptable to local contextual requirements. Future interoperability efforts, such as CHISs in general, are expected not only to move data efficiently but to strengthen community health systems in ways that measurably improve care.

The COVID-19 pandemic affected all WHO member states. We compared and contrasted the COVID-19 treatment guidelines of each member state with the WHO COVID-19 therapeutic guidelines.

Ministries of Health or accessed National Infectious Disease websites and other relevant bodies and experts were contacted to obtain national guidelines (NGs) for COVID-19 treatment. NGs were included only if they delineated specific pharmacological treatments for COVID-19, which were stratified by disease severity. We conducted a retrospective review using the adapted Reporting Checklist for Public Versions of Guidelines (RIGHT-PVG) survey checklist and a derived comparative metric based on the WHO guidelines was performed.

COVID-19 therapeutics NGs could be obtained from 109 of the 194 WHO member states. There was considerable variation in guidelines and in disease severity stratifications. Therapeutic recommendations in many NGs differed substantially from the WHO guidelines. Overall in late 2022, 93% of NGs were recommending at least one treatment which had proved to be ineffective in large randomised trials, and was not recommended by WHO. Corticosteroids were not recommended in severe disease in nearly 10% of NGs despite overwhelming evidence of their benefit. NGs from countries with low-resource settings showed the greatest divergence when stratified by gross domestic product per year, Human Development Index and the Global Health Security Index.

Our study is limited to NGs that were readily accessible, and it does not reflect the availability of recommended medicines in the field. Three years after the start of the SARS-CoV-2 pandemic, available COVID-19 NGs vary substantially in their therapeutic recommendations, often differ from the WHO guidelines, and commonly recommend ineffective, unaffordable or unavailable medicines.

Research and development (R&D) of new drugs and regimens against tuberculosis (TB) is evolving to meet new challenges and face limited investments in the sector. To effectively improve and fill existing gaps, researchers and trialists should engage a broad spectrum of stakeholders. With this study, we aim to map the interests in TB R&D raised by the main stakeholders in the TB field.

We conducted semistructured, short interviews to gather insight and viewpoints on innovation on TB drugs and regimens R&D of policy-makers, national TB programme officers, donors, funders, non-governmental organisations and research institutions.

A composite measure of the relevance of topics that emerged was computed by implementing different models considering the importance for researchers and the urgency to implement those changes during the trial, the number of citations each topic received, and the maximum value of the influence of stakeholders who had raised the topic.

50 stakeholders, out of 56 identified, were interviewed and almost half were policy-makers and governmental institutions. Several stakeholders highlighted the importance of disseminating information about clinical trials’ methodology and emerging preliminary results, followed by the need to pursue early discussion around access and pricing of safe and effective TB innovations, although different categories of stakeholders prioritised different topics. Using different methods for ranking topics, the results remained almost unchanged. Notably, post-trial operational research ranked higher in models with higher weight for the parameter considering the number of citations.

Researchers and research consortia embarking on phase 2 and 3 clinical trials should consider a broad set of elements when planning and designing trials’ protocols, all aiming at lowering the price and improving access to emerging TB innovations, besides meeting regulatory criteria. This can only be achieved by consulting and engaging relevant stakeholders in the discussion.

To examine the impact of the COVID-19 pandemic on mortality, we estimated excess all-cause mortality in 24 countries for 2020 and 2021, overall and stratified by sex and age.

Total, age-specific and sex-specific weekly all-cause mortality was collected for 2015–2021 and excess mortality for 2020 and 2021 was calculated by comparing weekly 2020 and 2021 age-standardised mortality rates against expected mortality, estimated based on historical data (2015–2019), accounting for seasonality, and long-term and short-term trends. Age-specific weekly excess mortality was similarly calculated using crude mortality rates. The association of country and pandemic-related variables with excess mortality was investigated using simple and multilevel regression models.

Excess cumulative mortality for both 2020 and 2021 was found in Austria, Brazil, Belgium, Cyprus, England and Wales, Estonia, France, Georgia, Greece, Israel, Italy, Kazakhstan, Mauritius, Northern Ireland, Norway, Peru, Poland, Slovenia, Spain, Sweden, Ukraine, and the USA. Australia and Denmark experienced excess mortality only in 2021. Mauritius demonstrated a statistically significant decrease in all-cause mortality during both years. Weekly incidence of COVID-19 was significantly positively associated with excess mortality for both years, but the positive association was attenuated in 2021 as percentage of the population fully vaccinated increased. Stringency index of control measures was positively and negatively associated with excess mortality in 2020 and 2021, respectively.

This study provides evidence of substantial excess mortality in most countries investigated during the first 2 years of the pandemic and suggests that COVID-19 incidence, stringency of control measures and vaccination rates interacted in determining the magnitude of excess mortality.

Neonatal mortality is a global public health challenge. Guatemala has the fifth highest neonatal mortality rate in Latin America, and Indigenous communities are particularly impacted. This study aims to understand factors driving neonatal mortality rates among Maya Kaqchikel communities.

We used sequential explanatory mixed methods. The quantitative phase was a secondary analysis of 2014–2016 data from the Global Maternal and Newborn Health Registry from Chimaltenango, Guatemala. Multivariate logistic regression models identified factors associated with perinatal and late neonatal mortality. A number of 33 in-depth interviews were conducted with mothers, traditional Maya midwives and local healthcare professionals to explain quantitative findings.

Of 33 759 observations, 351 were lost to follow-up. There were 32 559 live births, 670 stillbirths (20/1000 births), 1265 (38/1000 births) perinatal deaths and 409 (12/1000 live births) late neonatal deaths. Factors identified to have statistically significant associations with a higher risk of perinatal or late neonatal mortality include lack of maternal education, maternal height <140 cm, maternal age under 20 or above 35, attending less than four antenatal visits, delivering without a skilled attendant, delivering at a health facility, preterm birth, congenital anomalies and presence of other obstetrical complications. Qualitative participants linked severe mental and emotional distress and inadequate maternal nutrition to heightened neonatal vulnerability. They also highlighted that mistrust in the healthcare system—fueled by language barriers and healthcare workers’ use of coercive authority—delayed hospital presentations. They provided examples of cooperative relationships between traditional midwives and healthcare staff that resulted in positive outcomes.

Structural social forces influence neonatal vulnerability in rural Guatemala. When coupled with healthcare system shortcomings, these forces increase mistrust and mortality. Collaborative relationships among healthcare staff, traditional midwives and families may disrupt this cycle.

Proc Natl Acad Sci U S A. 2024 Apr 23;121(17):e2403206121. doi: 10.1073/pnas.2403206121. Epub 2024 Apr 17.

ABSTRACT

Mycobacterium abscessus is increasingly recognized as the causative agent of chronic pulmonary infections in humans. One of the genes found to be under strong evolutionary pressure during adaptation of M. abscessus to the human lung is embC which encodes an arabinosyltransferase required for the biosynthesis of the cell envelope lipoglycan, lipoarabinomannan (LAM). To assess the impact of patient-derived embC mutations on the physiology and virulence of M. abscessus, mutations were introduced in the isogenic background of M. abscessus ATCC 19977 and the resulting strains probed for phenotypic changes in a variety of in vitro and host cell-based assays relevant to infection. We show that patient-derived mutational variations in EmbC result in an unexpectedly large number of changes in the physiology of M. abscessus, and its interactions with innate immune cells. Not only did the mutants produce previously unknown forms of LAM with a truncated arabinan domain and 3-linked oligomannoside chains, they also displayed significantly altered cording, sliding motility, and biofilm-forming capacities. The mutants further differed from wild-type M. abscessus in their ability to replicate and induce inflammatory responses in human monocyte-derived macrophages and epithelial cells. The fact that different embC mutations were associated with distinct physiologic and pathogenic outcomes indicates that structural alterations in LAM caused by nonsynonymous nucleotide polymorphisms in embC may be a rapid, one-step, way for M. abscessus to generate broad-spectrum diversity beneficial to survival within the heterogeneous and constantly evolving environment of the infected human airway.

PMID:38630725 | DOI:10.1073/pnas.2403206121

Nigeria is committed to reducing industrial trans-fatty acids (iTFA) from the food supply, but the potential health gains, costs and cost-effectiveness are unknown.

The effect on ischaemic heart disease (IHD) burden, costs and cost-effectiveness of a mandatory iTFA limit (≤2% of all fats) for foods in Nigeria were estimated using Markov cohort models. Data on demographics, IHD epidemiology and trans-fatty acid intake were derived from the 2019 Global Burden of Disease Study. Avoided IHD events and deaths; health-adjusted life years (HALYs) gained; and healthcare, policy implementation and net costs were estimated over 10 years and the population’s lifetime. Incremental cost-effectiveness ratios using net costs and HALYs gained (both discounted at 3%) were used to assess cost-effectiveness.

Over the first 10 years, a mandatory iTFA limit (assumed to eliminate iTFA intake) was estimated to prevent 9996 (95% uncertainty interval: 8870 to 11 118) IHD deaths and 66 569 (58 862 to 74 083) IHD events, and to save US$90 million (78 to 102) in healthcare costs. The corresponding lifetime estimates were 259 934 (228 736 to 290 191), 479 308 (95% UI 420 472 to 538 177) and 518 (450 to 587). Policy implementation costs were estimated at US$17 million (11 to 23) over the first 10 years, and US$26 million USD (19 to 33) over the population’s lifetime. The intervention was estimated to be cost-saving, and findings were robust across several deterministic sensitivity analyses.

Our findings support mandating a limit of iTFAs as a cost-saving strategy to reduce the IHD burden in Nigeria.

Global South researchers struggle to publish in Global North journals, including journals dedicated to research on health professions education (HPE). As a consequence, Western perspectives and values dominate the international academic landscape of HPE. This study sought to understand Global South researchers’ motivations and experiences of publishing in Global North journals.

This study used a hermeneutic phenomenological perspective. Unstructured interviews were conducted with 11 authors from 6 Global South countries. Interview transcripts were analysed through a process of familiarisation, identifying significant statements, formulating meanings, clustering themes, developing exhaustive descriptions, producing a fundamental structure and seeking verification.

Participants described being motivated by local institutional expectations, to improve reputation, to meet Global North perceptions of quality and to draw attention to their Global South context. Participants described experiences where their work was deemed irrelevant to Global North audiences, they were unable to interpret rejections and had learnt to play the publishing game by attending to both local and global imperatives. These motivations and experiences revealed several practical, academic and transformational tensions that Global South authors faced.

The tensions and negotiations encountered by Global South authors who publish in HPE journals reflect a ‘border consciousness’ whereby authors must shift consciousness, or become ‘shapeshifters’, inhabiting two or more worlds as they cross borders between the Global South and Global North conventions. There is an added burden and risk in performing this shapeshifting, as Global South authors stand astride the borders of two worlds without belonging fully to either.

Race and gender were intimately intertwined aspects of the colonial project, used as key categories of hierarchisation within both colonial and modern societies. As such, true decolonisation is only possible when both are addressed equally; failure to address the colonial root causes of gender-based inequalities will allow for the perpetuation of racialised notions of gender to persist across the global health ecosystem. However, the authors note with concern the relative sidelining of gender within the decolonising global health discourse, especially as it navigates the critical transition from rhetoric to action.

A scoping review was conducted to locate where gender does, or does not, appear within the decolonising global health literature. The authors reviewed the decolonising global health literature available on Scopus and PubMed online databases to identify peer-reviewed papers with the search terms "(decoloni* or de-coloni*) OR (neocolonial or neo-colonial) AND ‘global health’" in their title, abstract or keywords published by December 2022.

Out of 167 papers on decolonising global health, only 53 (32%) had any reference to gender and only 26 (16%) explicitly engaged with gender as it intersects with (de)coloniality. Four key themes emerged from these 26 papers: an examination of coloniality’s racialised and gendered nature; how this shaped and continues to shape hierarchies of knowledge; how these intertwining forces drive gendered impacts on health programmes and policies; and how a decolonial gender analysis can inform action for change.

Historical legacies of colonisation continue to shape contemporary global health practice. The authors call for the integration of a decolonial gender analysis in actions and initiatives that aim to decolonise global health, as well as within allied movements which seek to confront the root causes of power asymmetries and inequities.

Non-communicable diseases (NCDs) are a leading health and development challenge worldwide. Since 2015, WHO and the United Nations Development Programme have provided support to governments to develop national NCD investment cases to describe the socioeconomic dimensions of NCDs. To assess the impact of the investment cases, semistructured interviews and a structured process for gathering written feedback were conducted between July and October 2022 with key informants in 13 countries who had developed a national NCD investment case between 2015 and 2020. Investment cases describe: (1) the social and economic costs of NCDs, including their distribution and projections over time; (2) priority areas for scaled up action; (3) the cost and returns from investing in WHO-recommended measures to prevent and manage NCDs; and (4) the political dimensions of NCD responses. While no country had implemented all the recommendations set out in their investment case reports, actions and policy changes attributable to the investment cases were identified, across (1) governance; (2) financing; and (3) health service access and delivery. The pathways of these changes included: (1) stronger collaboration across government ministries and partners; (2) advocacy for NCD prevention and control; (3) grounding efforts in nationally owned data and evidence; (4) developing mutually embraced ‘language’ across health and finance; and (5) elevating the priority accorded to NCDs, by framing action as an investment rather than a cost. The assessment also identified barriers to progress on the investment case implementation, including the influence of some private sector entities on sectors other than health, the impact of the COVID-19 pandemic, and changes in senior political and technical government officials. The results suggest that national NCD investment cases can significantly contribute to catalysing the prevention and control of NCDs through strengthening governance, financing, and health service access and delivery.