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Substance use behaviours among sexual and gender minorities with a history of adverse childhood experiences: a systematic review and narrative-synthesis.
Get PDFBACKGROUND AND AIMS: Adverse childhood experiences (ACEs) are linked to poor behavioural and mental health outcomes, including substance use, and disproportionately affect sexual and gender minorities (SGM). However, the relationship between ACEs and substance use in this population remains underexplored. This review investigates associations between ACEs and substance use outcomes in SGM adults. DESIGN: Registered with PROSPERO (CRD42024493936), we systematically searched six databases from inception to 13 April 2025. Following PRISMA guidelines, two authors independently screened studies and extracted data comparing substance use outcomes in SGM adults with and without ACEs histories. Due to heterogeneity, we conducted a narrative synthesis. Risk of bias was assessed using the 2019 Mixed Methods Appraisal Tool (MMAT). PARTICIPANTS AND MEASUREMENTS: Included studies involved SGM adults (≥18 years) who experienced at least one ACEs before age 18. SGM status encompassed lesbian, gay, bisexual, transgender, queer, intersex, non-binary, and other identities. Outcomes included any substance use (drug, alcohol, tobacco), with ACEs exposure as the primary variable. FINDINGS: Thirty-two studies (N = 43,197) were included. Twenty-nine epidemiological studies showed consistent associations between ACEs and negative substance use outcomes across SGM sub-groups and substances. Three qualitative studies highlighted links between substance use and child sexual abuse, heterosexism, and intersecting oppressions such as racism and institutionalization. CONCLUSIONS: ACEs are associated with adverse substance use outcomes in SGM adults. Further research is needed on how intersecting marginalizations shape these associations
Rapid diagnosis of skin and soft tissue melioidosis in children.
Get PDFMelioidosis is an endemic infection caused by Burkholderia pseudomallei, found in tropical and subtropical regions. In resource-limited settings, culture-based diagnostics are often slow, delaying appropriate treatment, or unavailable. We conducted an interventional ambispective cohort study to assess the impact and diagnostic accuracy of the Active Melioidosis Detect Plus rapid diagnostic test (AMD-RDT) in Cambodian children with suspected skin and soft tissue melioidosis (SST-M). The retrospective cohort (July 2022-July 2023) received standard diagnostics; the prospective cohort (July 2023-December 2024) included AMD-RDT testing. Twenty-five retrospective culture-confirmed participants and 107 participants (31 culture-confirmed) in the prospective arm were analysed. Median time from pus collection to appropriate antibiotic initiation was 118.4 hours in the retrospective arm and 14.4 hours in the prospective arm (p = 0.057). Disseminated melioidosis workups were completed for 24% (6/25) and 80.6% (25/31) of retrospective and prospective participants respectively (p < 0.001), and detected two children with bacteraemia and three with intra-abdominal abscesses in the prospective arm. The AMD-RDT achieved a sensitivity of 90.3% (95% CI: 74.2-98.0%), specificity of 100% (95% CI: 95.3-100%), and an area under the receiver operating characteristic curve (AUC) of 0.95 (95% CI 0.89-1.00). Incorporating the AMD-RDT into the routine diagnostic pathway was associated with a reduction in time to effective antibiotic therapy and an increase in the proportion of participants completing a comprehensive diagnostic workup for systemic involvement. The high accuracy and rapid turnaround time support its use in resource-limited settings
Implementation and evaluation of the Y-Check comprehensive adolescent health check-up intervention in Zimbabwe: a pre-post mixed-methods study.
Get PDFRoutine adolescent health check-ups can support healthy development and well-being, but evidence on the feasibility, acceptability and effectiveness of contextually relevant comprehensive check-ups in low- and middle-income settings is limited. We conducted a hybrid implementation-effectiveness study incorporating a mixed-methods pre-post design of Y-Check, a comprehensive health check-up intervention in Zimbabwe, as part of a multicountry study developed and coordinated by the World Health Organization. Eligible participants were 10-19-year-old adolescents attending school or community venues. We used self-administered digital questionnaires, provider-led clinical tests and nurse reviews to screen for 25 conditions/behaviors. We provided health promotion, on-site care and referral to relevant providers. From October 2022 to September 2023, 2,097 adolescents were enrolled, of whom 1,843 (87.9%) were seen at 6 months. The primary outcome of appropriate care and/or referral(s) for all identified issues was achieved for 70.8% (95% confidence interval: 68.7-72.9%) of 1,865 participants with at least one issue. At follow-up, there were improvements in nutrition, health-related quality of life, self-esteem, behaviors and educational outcomes. The intervention was feasible and largely acceptable. Uptake of referral services varied by issue. Y-Check cost US$47 per participant. Through Y-Check, we identified untreated conditions and risk behaviors and successfully treated and linked adolescents to services. Here we provide evidence on the potential of the intervention to positively impact health and well-being
Comparison of laboratory-based and non-laboratory-based WHO and GLOBORISK CVD risk scores: A cross-sectional analysis of the APCAPS cohort.
Get PDFBACKGROUND AND AIM: Cardiovascular diseases (CVDs) represent a growing public-health challenge in India, where nearly one in four deaths is CVD-related. Accurate risk stratification underpins targeted prevention, yet laboratory-dependent tools are often impractical in resource-limited settings. The World Health Organization (WHO) and GLOBORISK initiatives both offer non-laboratory-based 10-year CVD risk algorithms alongside their laboratory-based counterparts. We aimed to compare laboratory- and non-laboratory-based WHO and GLOBORISK CVD risk scores, assess their concordance, and examine relationships with sub-clinical atherosclerosis in a rural Indian cohort. MATERIALS AND METHODS: We conducted a cross-sectional analysis of 2,465 adults (1,184 men, 1,281 women) aged 40-74 years from the third wave (2010-12) of the Andhra Pradesh Children and Parents Study (APCAPS). Participants with prior CVD were excluded. Ten-year CVD risk was calculated using sex-specific WHO (South Asia) and India-calibrated GLOBORISK models, both laboratory-based (age, sex, smoking, systolic blood pressure, diabetes, total cholesterol) and non-laboratory-based (age, sex, smoking, systolic blood pressure, BMI) algorithms. Categorical agreement was quantified via percentage agreement and quadratic weighted kappa (κ); continuous agreement by Bland-Altman analysis. We also evaluated linear associations between each risk score (categorical and continuous) and three sub-clinical atherosclerosis markers: carotid intima-media thickness (CIMT), pulse-wave velocity (PWV), and augmentation index (AIx), through sex-stratified multi-level linear regression with random intercept at the household level, adjusting for multiple testing (p < 0.01). RESULTS: Median WHO-CVD-risk was 6.0% (IQR 4% - 9%) in men and 3.0% (2% - 4%) in women for both lab and non-lab models; median GLOBORISK-CVD-risk was 12.0% (9% - 16%) for lab-model vs. 15.0% (10% - 16%) for non-lab-model in men and 5.0% (3% - 9%) for lab-model vs. 5.0% (3% - 9%) for non-lab-model in women. Categorical agreement was substantial to almost perfect: WHO κ = 0.82 (overall), GLOBORISK κ = 0.72. Bland-Altman analyses demonstrated mean differences <1% between lab- and non-lab-based scores, though non-lab models underestimated risk by 4.2% in diabetics and 1.2% in participants with total cholesterol ≥200 mg/dL. Both risk scores showed positive, dose-response relationships with CIMT, PWV, and AIx (p-trend<0.001), with each SD increase in CVD-scores associated with clinically meaningful increases in all three markers of sub-clinical atheroscerosis. CONCLUSION: Non-laboratory-based WHO and GLOBORISK CVD risk scores exhibit high overall agreement with laboratory-based models and correlate strongly with subclinical atherosclerosis in rural India. However, modest underestimation in high-risk subgroups (diabetics, hypercholesterolemia) warrants cautious interpretation. These findings support the feasibility of non-lab risk assessment in resource-constrained settings, while underscoring the need for prospective validation against hard cardiovascular outcomes prior to large-scale implementation
Evaluation of the protective efficacy of a transfluthrin-based spatial repellent product to reduce malaria prevalence in Uganda: study protocol for a cluster-randomised double-blinded control trial-the Mossie-GO trial.
No full textBACKGROUND: Progress towards elimination and eventual eradication of malaria is threatened by challenges such as the rise in insecticide resistance and low coverage of existing vector control tools. Spatial repellents offer personal and household protection against biting mosquitoes by disseminating repellents into a given area. The trial described here aims to evaluate the efficacy of an active transfluthrin-based spatial repellent device (Mossie-GO™) against malaria in Uganda, using a placebo-controlled, double-blinded cluster randomised control trial. The study's primary objective is to demonstrate and quantify the protective efficacy of Mossie-GO™ in reducing the prevalence of malaria infection in children ≤ 5 years of age. The study's secondary objectives are to measure the impact of the intervention on entomological correlates of transmission, to determine user acceptance of the device and to quantify transfluthrin concentration in the air.
METHODS: The trial has fifty-six clusters randomly assigned in a 1:1 ratio to either the intervention or placebo-control arm. One hundred children at baseline and sixty children ≤ 5 years of age will be sampled in each cluster at 6 and 12 months to measure the primary endpoint. Each child will be sampled from a different household to avoid within-house replication. A subset of households from each cluster will be selected for secondary endpoint sampling. All households enrolled into the study will be encouraged to continue use of other malaria control tools.
DISCUSSION: Trial results will contribute to the growing research on spatial repellent efficacy in sub-Saharan Africa and will inform recommendations for the use of spatial repellents in malaria control, specific to rural and peri-urban contexts in Uganda. Information on household characteristics, behaviour related to malaria exposure and user acceptability of the intervention will also be collected to improve understanding of the intervention usage and impact. Following the trial, results will be publicly disseminated.
TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov 01/04/2024 unique identification (ID): NCT06232954
Empagliflozin in Heart Failure and Previous Coronary Revascularization: Insights From EMPEROR-Pooled.
Get PDFBACKGROUND: Sodium glucose co-transporter-2 inhibitors are a foundational therapy for the management of chronic heart failure (HF).
OBJECTIVES: The purpose of this study was to investigate whether the efficacy of sodium glucose co-transporter-2 inhibitors in patients with HF is maintained in patients with a history of coronary revascularization.
METHODS: The EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure (EMPEROR)-Pooled database was a prospectively designed pooled analysis of the EMPEROR-Reduced (NCT03057977) and EMPEROR-Preserved (NCT03057951) trials, which randomized patients with HF with a left ventricular ejection fraction below and above 40%, respectively, to empagliflozin or placebo. The primary outcome was time to first HF hospitalization or cardiovascular death. We studied the baseline risk of revascularized HF patients and the impact of previous revascularization on the efficacy and safety of empagliflozin.
RESULTS: Overall, 3,437/9,718 (35.4%) had a history of coronary revascularization with either percutaneous coronary intervention or coronary artery bypass grafting (REVASC), and 6,281/9,718 (64.6%) did not (no REVASC). The median follow-up time was 21.23 months (IQR: 14.93-28.97 months). Of those randomized to placebo, a history of revascularization was not associated with an elevated risk of clinical outcomes, including the primary outcome and 3-point major adverse cardiac and cerebrovascular event. The efficacy and safety of empagliflozin were consistent irrespective of revascularization history for all major outcomes (primary outcome: REVASC: 0.76 [0.66-0.89], no REVASC: 0.77 [0.68-0.87], Pinteraction: 0.94). Empagliflozin had neutral effect on a 3-point major adverse cardiac and cerebrovascular event in both groups.
CONCLUSIONS: In this large HF trial program, revascularized patients with HF exhibited similar rates of HF and ischemic events as those without prior revascularization. The efficacy and safety of empagliflozin in HF were consistent in those with and without a revascularization history
The impact of tuberculosis and its treatment on the lung and gut microbiota: a global systematic review, meta-analysis, and amplicon-based metagenomic meta-analysis.
Get PDFBACKGROUND: Tuberculosis (TB) remains the leading cause of bacterial disease-related mortality worldwide. While Koch’s single-agent model has long guided TB diagnostics and treatment, metagenomic studies reveal a resident lung microbiome disrupted by TB and its orally administered therapy, with downstream effects on the gut microbiome. Understanding these disruptions may uncover diagnostic and prognostic indicators. We systematically reviewed 38 studies involving 3394 individuals with TB and healthy controls across four continents to assess the impact of TB and its treatment on lung and gut microbiome diversity, structure, and composition. A meta-analysis of 29 studies and a patient-level amplicon metagenomic meta-analysis (AMMA) of 1617 individuals (1.3 billion reads) were conducted following PRISMA guidelines [PROSPERO: CRD42022329763]. RESULTS: No global consensus exists on TB's impact on lung microbial diversity. Pooled estimates suggest a reduction of ~0.14 in lung diversity and 0.41 in gut diversity. Patient-level analyses showed no overall significant difference in lung diversity (Shannon index), though reductions were evident in China but not South Africa. Conversely, gut diversity tended to be higher in TB cases. Disease status explained only 0.8–9% of variation in lung microbiota and 1.8–9% in gut communities. Composition-wise, TB was associated with depletion of anaerobic core lung genera (e.g. Prevotella, Neisseria, Veillonella, Haemophilus, Fusobacterium, Pseudomonas, Streptococcus, Porphyromonas, Treponema) and gut genera (e.g. Prevotella, Ruminococcus, Faecalibacterium, Clostridium, Roseburia, Rothia, Eubacterium, Escherichia). Treatment further reduced diversity at both sites, with additional loss of core taxa. CONCLUSION: TB is generally linked to reduced lung microbial diversity but increased gut diversity, with effects varying by country, suggesting context-specific rather than universal microbial signatures. Treatment consistently decreases diversity in both lung and gut. Although findings here primarily reflect the upper respiratory tract, they highlight potentially exploitable microbial dynamics. Future studies should integrate additional diversity metrics and broader metadata to refine these insights for advancing their clinical utility. CLINICAL TRIAL: Not applicable. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-025-12369-1
Treat-to-Target Urate-Lowering Treatment and Cardiovascular Outcomes in Patients With Gout.
Get PDFIMPORTANCE: Gout is associated with increased cardiovascular risk. Whether achieving a target serum urate level lower than 6 mg/dL with urate-lowering treatment (ULT) would reduce cardiovascular risk in patients with gout is unknown. OBJECTIVES: To evaluate the association between achieving a serum urate treatment target lower than 6 mg/dL and cardiovascular events among patients with gout who were newly prescribed ULT. DESIGN, SETTING, AND PARTICIPANTS: This new-user cohort study using emulated target trial framework with up to 5-year follow-up was performed using primary care data from the Clinical Practice Research Datalink Aurum linked to hospitalization and mortality records from January 1, 2007, to March 29, 2021. Patients were 18 years or older, diagnosed with gout, had a pretreatment serum urate level higher than 6 mg/dL, and were newly prescribed ULT. Data were analyzed from May 2024 to January 2025. EXPOSURE: Patients were assigned to the treat-to-target (T2T) ULT arm or the non-T2T ULT arm if they achieved or did not achieve a serum urate level lower than 6 mg/dL, respectively, within 12 months of their first ULT prescription. MAIN OUTCOMES AND MEASURES: The primary outcome was first major adverse cardiovascular event within 5 years of first ULT prescription. Gout flare was the positive control outcome. Acute bronchitis, cataract, and appendicitis were included as negative control outcomes. Weighted absolute 5-year event-free survival and weighted hazard ratios (HRs) with 95% CIs were estimated. RESULTS: Of 109 504 patients included, the mean (SD) age was 62.9 (15.2) years, 22.2% were female, the mean (SD) disease duration was 2.5 (3.6) years, and 27.3% were included in the T2T ULT arm. Patients in the T2T ULT arm had a higher 5-year survival (weighted survival difference, 1.0%; 95% CI, 0.5%-1.6%) and lower risk of major adverse cardiovascular events (weighted HR, 0.91; 95% CI, 0.89-0.92) than those in the non-T2T ULT arm. There was a greater association for people at high and very high cardiovascular risk than those with moderate risk. Patients who achieved a lower serum urate target of less than 5 mg/dL had a larger risk reduction (weighted survival difference, 2.6%; 95% CI, 0.9%-3.6%; weighted HR, 0.77; 95% CI, 0.72-0.81). Patients in the T2T ULT arm had fewer gout flares. No differences were observed for negative control outcomes. CONCLUSIONS AND RELEVANCE: In this cohort study among patients with gout who were newly prescribed ULT, achieving serum urate levels lower than 6 mg/dL within 12 months was associated with a lower 5-year risk of major adverse cardiovascular events
Identification of claramine and anidulafungin as entry inhibitors of Crimean-Congo hemorrhagic fever virus.
Get PDFCrimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne enveloped virus that causes a severe disease in humans. Despite its wide geographic distribution, no approved vaccines or therapeutics exist. In this study, we achieved high-titer production of pseudotyped virus bearing CCHFV glycoproteins with a C-terminal truncation. Screening over 3,600 small compounds using this pseudotyped virus identified claramine and anidulafungin as CCHFV entry inhibitors. These hit compounds, as well as caspofungin, which is related to anidulafungin, inhibited pseudotyped viral infection in human liver cells and vascular endothelial cells. They inhibited infection of pseudotyped virus with glycoproteins from various CCHFV strains and Hazara virus, a nairovirus closely related to CCHFV. Using a quantitative fusion assay, the identified inhibitors were shown to block membrane fusion via CCHFV glycoproteins. Moreover, they inhibited infection of replication-competent Hazara virus. Therefore, the assays developed in this study were successful in identifying CCHFV entry inhibitors that target membrane fusion
Perceived gender equitable norms and previous tuberculosis testing in Malawi: A secondary analysis of a cluster-based prevalence survey.
Get PDFSubstantial evidence demonstrates that men have a higher prevalence of tuberculosis (TB) and decreased use of TB services compared to women. Gender roles and norms contribute to these disparities by influencing social and structural determinants, as well as individual behaviours. In this analysis, we investigated attitudes towards gender equitable norms and TB testing behaviours amongst Malawian men and women participating in a prevalence survey conducted before a community-based TB active case finding trial in Blantyre. Attitudes towards equitable gender norms were captured through a modified version of the Gender Equitable Men Scale (GEMS). Gender inequitable views were prevalent among both men (56.1%) and women (55.8%). The association between a composite GEMS score and TB testing history was modelled using logistic regression, accounting for various sociodemographic covariates (age, sex, wealth quantile, education, and HIV status) (OR = 1.12, 95% CI: 0.88-1.42, p = 0.373). Bivariate analysis demonstrated no notable confounding by any covariates and no strong effect modification. While GEMS score had no association with TB testing history among women, men with higher GEMS scores (less gender-equitable views) were more likely to have been tested for TB across age groups. These findings provide a basis for future investigation into the patterns and motives TB behaviours, particularly in older men. Tailored public health strategies may then be implemented to address this important population