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Isoniazid preventive therapy modulates Mycobacterium tuberculosis-specific T-cell responses in individuals with latent tuberculosis and type 2 diabetes
Get PDFDiabetes mellitus (DM) is a significant contributor to tuberculosis (TB) incidence and poor treatment outcomes. This study explored the impact of isoniazid preventive therapy (IPT) on Mycobacterium tuberculosis (Mtb)-specific T-cell memory phenotypes and function among participants with latent TB infection and DM (LTBI-DM) at baseline and after 6 months of IPT; and compared the responses to healthy controls (HC). Peripheral blood mononuclear cells were stimulated with ESAT-6 and CFP-10 peptide pools to analyse CD4+ and CD8+ T-cell responses using flow cytometry. In LTBI-DM participants, effector memory CD4+ and CD8+ T cells were decreased post-IPT, suggesting a shift towards a less-activated state or differentiation into other subsets. CXCR5 expression on both CD4+ and CD8+ T cells was upregulated, while PD-1 expression was downregulated post-IPT, indicating reduced T-cell exhaustion and improved homing capabilities. Lastly, IL-17 A and IL-13 production in CD4+ and CD8+ T cells was increased post-IPT, respectively, which play a role in enhanced Mtb infection control. The post-IPT T-cell alterations were similar to normal HC levels. These findings suggest that IPT modulates and normalises specific T-cell memory phenotypes and functional responses in LTBI-DM participants, potentially contributing to improved long-term immunity and protection against TB. This study highlights the importance of preventive therapy in high-risk populations, and larger studies with more extended follow-up are needed to assess long-lasting IPT effects
Semi-automated screening reveals patients with glaucoma-induced blindness missing out on social support: a cross-sectional study of certificate of visual impairment allocation
Get PDFBACKGROUND/AIMS: Many countries provide social support to patients with severe sight impairment (blindness). In the UK, these benefits require a certificate of visual impairment (CVI) which requires referral by a consultant ophthalmologist. Many eligible patients do not receive a CVI due to personal choice or lack of consideration or communication by their doctor. This study investigated the frequency and reasons for missed certification in glaucoma.
METHODS: A retrospective cross-sectional survey was undertaken of all patients with glaucoma attending a tertiary referral clinic over a 12-month period. Semi-automated screening using objective visual acuity and perimetry parameters was facilitated by a web application, GFDC (Glaucoma Field Defect Classifier). CVI-eligible patients' records were analysed to determine the reasons for missed registration, including incorrect screening classification.
RESULTS: Of 5620 individual patients consulted, 919 were classified as sight impaired, and 64 were classified as severely sight impaired (blind). Of the patients classified as blind, 7 (11%) were misclassified, and 36 (56%) were on the CVI register already. 21 of 57 eligible patients with glaucoma-induced blindness (37%) were unregistered. Reasons for missed registration included administrative failure (23.8%), lack of consent (9.5%), reversible visual impairment (19.0%), frailty and comorbidity (71.4%), and mental health diagnoses (38.1%).
CONCLUSION: A semi-automated algorithm can be used to screen large numbers of patients for CVI eligibility due to blindness. Many eligible patients are not registered, with risk factors including frailty, comorbidity and reversible causes of visual impairment. This algorithm could be used to prompt ophthalmologists to consider registration or used as an alternative referral mechanism. Screening for CVI-eligible patients with an objective algorithm may ameliorate the inequity associated with subjective and variable decision-making
Who gets funded? Global analysis of research funding for newborn health and stillbirth in fragile and non-English speaking countries, 2016–2020
Get PDFContext: Despite global progress toward the Sustainable Development Goals (SDGs), 2.3 million newborn deaths and 1.9 million stillbirths occur each year, with a disproportionate burden in humanitarian and fragile contexts. We investigated how funding for newborn health research during the SDG period (2016–2020) varied according to country fragility and language.
Methods: We conducted a systematic analysis of research grants using the Dimensions database, classifying grants
by research theme, stage of the research process, type of funding agency, and classification of donor and recipient countries according to the World Bank’s income ranking. The grants were then analyzed according to the Fragile States Index and the official languages of the recipient countries.
Results: Between 2016 and 2020, USD 308.2 million was awarded across 1,372 grants involving at least one low-or middle-income recipient country (LMIC). Of this amount, 35% (USD 108.0 million) funded grants involving both an LMIC and a recipient from one of the 30 most fragile countries, while only 19% (USD 57.3 million) was awarded directly to organizations based in the 30 most fragile countries. Among these recipients from fragile states, most funding supported intervention research (USD 33.6 million), with minimal investment in implementation (USD 5.0 million) or basic science (USD 2.8 million). Linguistic disparities were evident: of all grants, recipients from English-speaking countries received the largest amount (USD 115.5 million).
Interpretation: Significant inequalities persist in the allocation of funding for research on newborn health and stillbirths. Despite bearing a disproportionate burden of neonatal mortality, organizations in non-English-speaking countries and the 30 most fragile countries have received limited research funding. These disparities contribute to gaps in evidence regarding impact in humanitarian settings, hinder implementation, and exacerbate global inequalities in research and health
Comprehensive sexuality education addressing gender and power: a systematic review of intervention effects
Get PDFComprehensive sexuality education (CSE), including critical reflection on gender norms and unfavourable power relations, has been theorised to affect various health and social outcomes among adolescents. This systematic review aimed to synthesise evidence on the effectiveness of school-based CSE addressing gender and power topics on adolescents’ sexual and reproductive health (SRH) and relationships outcomes. We screened six databases for evaluations of school-based CSE programmes. We included outcome evaluations of interventions addressing SRH, gender, and power through a critical reflection and empowerment approach. Intervention effects were synthesised in effect direction plots. We identified 12 articles evaluating 11 interventions in four countries. Positive effects were found for most healthy relationships outcomes and for outcomes related to adolescents’ SRH knowledge, attitudes, and intentions. Effects on SRH behaviours were more mixed. CSE programmes addressing gender and power appeared more effective than sexuality education without this content. Gender roles and norms play a crucial role in shaping adolescents’ relationships and should be addressed as part of a comprehensive approach to sexuality education. However, in the light of some inconclusive outcomes, CSE with gender and power content needs to be more rigorously evaluated than hitherto in more diverse social and cultural contexts
'Hell No!'-Exploring Scepticism in UK Health Research Since COVID-19 Amongst Communities Who Have Been Labelled 'Underserved'.
Get PDFHealthcare research globally has seen a renewed shift to increase diversity in research participation. People previously excluded from the production of biomedical knowledge, and often labelled 'underserved', are now a focus of attention. In this paper we discuss an in-depth interview study in South London which aimed to better understand how the very public era of COVID-19 research has affected people's trust, opinions and relationships with health research, focusing on hearing from those with intersectional experiences of inequality and injustice. We suggest that 'underserved', much like 'diversity', obscures historically rooted injustice with narratives of what Chandra Talpade Mohanty calls 'benign variation' and assumptions that health research has always worked in service to others. Rather, we draw on the work of Sara Ahmed to ensure we take participants' concerns, scepticisms or complaints about research seriously. Drawing on participants' narratives of health injustice, we document how participants embody critical dispositions, which demand more complex understandings of health research that incorporate doubts, nuance and multiple sources. Such accounts render into stark relief the underlying power relations in attempts to simplify research participation narratives. This study demonstrates research institutions need to engage in more complex dialogue with communities in order to be worthy of trust
Socioeconomic markers of dengue mortality in the 100 Million Brazilian Cohort (2007-2018): A nationwide registry-based cohort study.
Get PDFBACKGROUND: People living in economically disadvantaged circumstances experience higher risks of infections and death from arboviruses. However, more evidence is needed to better understand the socioeconomic factors influencing dengue mortality. We investigated if people of lower socioeconomic conditions in Brazil are more likely to die following dengue infection. METHODOLOGY/PRINCIPAL FINDINGS: Linking nationwide socioeconomic data from the 100 Million Brazilian Cohort with dengue disease and death records registered in Brazil between 1st January 2007 and 31st December 2018, we used multivariable hierarchical analysis to investigate the socioeconomic determinants of dengue-specific and all-cause mortality within 15 days of dengue symptom onset. Among the 3,018,131 individuals from the 100 Million Brazilian Cohort diagnosed with dengue, 1810 died from dengue (Case Fatality Rate (CFR)=0.06%, 95%CI = 0.06-0.06%) and 3076 (CFR = 0.10%, 95%CI = 0.10-0.11%) died from any cause within 15 days of dengue symptom onset. People residing in the Northeast (OR=2.32; 95%CI = 1.74-3.10) and Midwest (OR=1.68; 95%CI = 1.25-2.27) regions, self-identifying as black race/ethnicity (OR=1.58; 95%CI = 1.31-1.90), having lower level of education (OR=2.35, 95%CI = 1.17-4.73), being retired/receiving pension (OR=2.24; 95%CI = 1.76-2.86), living in a household with rudimentary sewage (OR=1.19; 95%CI = 1.04-1.37) and having >2 inhabitants per room (OR=1.31; 95%CI = 1.11-1.55) had at higher odds of dengue-specific mortality. Similar characteristics were also associated with higher all-cause mortality after dengue infection, but also included residing in North region (OR=1.60; 95%CI = 1.24-2.06) and rural areas (OR=1.12; 95%CI = 1.01-1.24), self-identifying as Asian (OR=1.65; 95%CI = 1.07-2.54) and mixed race/brown (OR=1.20; 95%CI = 1.10-1.31) and living in households with poorer quality building and sanitary conditions. CONCLUSIONS/SIGNIFICANCE: Our findings provide evidence that individuals in Brazil with lower socioeconomic condition experience increased odds of dengue-specific and all-cause mortality within 15 days of dengue symptom onset. These findings underscore the importance of ensuring equitable access to high-quality treatment for severe dengue and suggest that reducing poverty and social inequality, including through improvement of sanitation and housing, may help mitigate dengue-related mortality
Catheter and Surgical Ablation for Atrial Fibrillation : A Systematic Review and Meta-analysis.
Get PDFBACKGROUND: Ablation of atrial fibrillation can restore normal heart rhythm, but its effect on clinical outcomes is uncertain. PURPOSE: To determine the effect of ablation on ischemic stroke at more than 30 days (primary outcome). DATA SOURCES: Search of 9 databases without language restrictions from 1 January 1987 to 13 September 2024, and bridge search of 2 databases to 1 May 2025. STUDY SELECTION: Randomized controlled trials of catheter or surgical ablation versus no ablation that had at least 1 month of follow-up and reported stroke and/or mortality. DATA EXTRACTION: Dual independent data extraction and risk-of-bias assessment. DATA SYNTHESIS: Compared with medical therapy, catheter ablation reduced risks for ischemic stroke after 30 days (relative risk [RR], 0.63 [95% CI, 0.43 to 0.92]), mortality (RR, 0.73 [CI, 0.60 to 0.88]), and heart failure (HF) hospitalization (RR, 0.68 [CI, 0.55 to 0.85]). However, catheter ablation increased the RR for ischemic stroke at or before 30 days (6.81 [CI, 1.56 to 29.8]) such that the RRs were 0.77 (CI, 0.55 to 1.09) for any ischemic stroke and 0.77 (CI, 0.57 to 1.05) for all strokes. Surgical ablation reduced the RRs for ischemic stroke (0.54 [CI, 0.34 to 0.86]) and stroke from any cause (0.54 [CI, 0.35 to 0.82]) but had uncertain benefit for other outcomes; RRs were 0.63 (CI, 0.37 to 1.06) for ischemic stroke after 30 days, 0.90 (CI, 0.70 to 1.15) for mortality, and 0.90 (CI, 0.60 to 1.35) for HF hospitalization. LIMITATIONS: Clinical heterogeneity of trials, lack of participant-level data, and inclusion of unblinded trials. CONCLUSION: Catheter ablation reduced the risks for ischemic stroke at more than 30 days, mortality, and HF hospitalization. Surgical ablation had uncertain benefit, except for stroke. PRIMARY FUNDING SOURCE: National Center for Advancing Translational Sciences of the National Institutes of Health (Awards TL1TR002344 and UL1TR002345). (PROSPERO: CRD42023409751)
Embedding violence prevention in existing religious and education systems: initial learning from formative research in the Safe Schools Study in Zimbabwe.
Get PDFBACKGROUND: Few interventions to reduce violence against children in Catholic Church affiliated schools have been tested for effectiveness. We describe learning from formative research on the development of a school-based behavioural intervention aiming to reduce teacher violence and bullying, which originated from and is embedded within Catholic-run primary schools in Zimbabwe. Specifically, we aim to (1) describe and document the process of intervention development and refinement, including efforts to design the Safe Schools Programme to be embedded into existing religious, child protection, and education structures; (2) reflect on the opportunities and challenges of developing a violence prevention intervention for integration within existing education and religious systems; and (3) discuss the implications for scale-up and sustainability of violence prevention interventions. METHODS: We conducted multi-method research to understand the context of intervention implementation, the acceptability of the intervention, feasibility of the delivery model and to refine both the intervention content and underlying intervention theory of change. This included Theory of Change workshops with all study partners at three time-points, and focus groups, in-depth interviews, participatory workshops at two time-points. Participants in qualitative research included school headteachers, teachers, school staff, priests, students, parents, local government education actors, and child protection NGO staff. Qualitative data were analysed thematically. RESULTS: Findings reveal several challenges facing schools including low motivation of teachers due to high workload and inadequate school-based referral systems for child protection. Views on the acceptability of corporal punishment are polarised with some parents and teachers supporting its use despite the recent ban, presenting an opportunity for the intervention to support teachers move towards alternative discipline. Findings suggest that aligning intervention activities within existing structures within schools and using familiar teaching methods is an effective way to support intervention uptake while addressing concerns about teachers' workload and intervention acceptability. The intervention was refined in light of the qualitative findings and Theory of Change workshop reflections, which included: additional behaviour change engagement with teachers, an amendment of the school-based referral system, amendment of manual content for children, and streamlining of materials with existing workload. CONCLUSIONS: Interventions designed by 'insiders' at institutions such as the Catholic Church, have huge potential for implementation at a large scale due to systems and context expertise, pre-established relationships, and alignment with stakeholder priorities. However, such interventions should be mindful of power hierarchies and provide adequate support to equip actors with violence prevention expertise. Future research on violence prevention interventions designed by religious institutions and their implications for future scale-up and sustainability is recommended
Prevalence and progress of underdiagnosis of probable dementia: a repeated cross-sectional study in 19 European countries.
Get PDFBACKGROUND: Underdiagnosis of dementia remains a significant public health challenge in Europe, with nearly half of those meeting clinical criteria not receiving a formal diagnosis. Recent healthcare initiatives have aimed to improve diagnostic processes, but the extent of progress varies across countries. METHODS: We analyzed data of 10,402 participants from the Survey of Health, Ageing, and Retirement in Europe (SHARE) across 19 countries from 2011-2015 to 2015-2019. Underdiagnosis of probable dementia was defined as probable dementia (based on cognition score) without a confirmed diagnosis. Weighted logistic regression was conducted to examine temporal trends in underdiagnosis of probable dementia and to identify individual- and country-level predictors of progress in diagnosis. RESULTS: A significant reduction in underdiagnosis of dementia was observed between the two periods, consistent across most countries. Progress in diagnosis was modified by country-level factors such as number of psychiatrists, formal long-term care worker at home or institutions, and positron emission tomography and individual-level factors including age, education, retirement status, nursing home residency, multimorbidity, and healthcare utilization patterns. CONCLUSIONS: The decreasing trend in underdiagnosis highlights the importance of targeted interventions including investment in psychiatric care services. Understanding remaining disparities is crucial for informing health policies and addressing inequalities to dementia diagnosis and care
Effective coverage measurements and cascade for maternal, newborn, child and adolescent health in high-income countries: systematic review.
Get PDFBACKGROUND: The concept of 'effective coverage' (EC) aims to combine the concept of coverage with the quality of care delivered and, ultimately, the health benefits received by the population in need. To date, systematic reviews of EC of maternal, newborn, child and adolescent health (MNCAH) have focused on low- and middle-income countries (LMICs). No review has examined whether and how the concept has been applied in high-income countries (HICs). To address this gap, this systematic review investigated the application of EC measures in MNCAH care in HICs. METHODS: This was a systematic review that followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) reporting guidelines. The search strategy was developed from previous EC reviews conducted in LMICs and further adapted to the HIC setting. Additional search terms were identified through discussion with experts from the Life Stage Quality of Care Metrics Technical Working Group subgroup on EC. We searched three databases, PubMed, Embase, and Web of Science, over 10 years. We conducted additional searches in Google Scholar and by consulting members of the Life Stage Quality of Care Metrics Technical Working Group. We did not pose any language or type of article limits. RESULTS: The database search identified 18 976 studies for screening. Of these, 672 abstracts were screened, and none of the full texts considered met our inclusion criteria (e.g. human immunodeficiency virus/hepatitis c virus continuum of care cascade, intervention type, qualitative search-interviews/questionnaire type studies). Thirty-two articles were retrieved through the additional search strategies, and none were included because of LMIC-focused research. Therefore, examples of EC of MNCAH care applied in HICs were not identified. CONCLUSIONS: Further investigation should be conducted into the application of the EC concept for assessing MNCAH care in HICs. This research will help us understand how this concept can be used to support health system effectiveness, efficiency, and equity in HICs. REGISTRATION: The study protocol was registered at the Open Science Framework: https://doi.org/10.17605/OSF.IO/FMCG8