PLOS Medicine

BackgroundMost studies investigating the association between hospital staff levels and mortality have focused on single professional groups, in particular nursing. However, single staff group studies might overestimate effects or neglect important contributions to patient safety from other staff groups. We aimed to examine the association between multiple clinical staff levels and case-mix adjusted patient mortality in English hospitals. Methods and FindingsThis retrospective observational study used routinely available data from all 138 National Health Service hospital trusts that provided general acute adult services in England between 2015 and 2019. Standardised mortality rates were derived from the Summary Hospital level Mortality Indicator dataset. Estimates for the effect of clinical staffing from the single staff models were generally higher than estimates from models with multiple staff groups. Using a multilevel negative binomial random effects model, hospitals with higher levels of medical and allied healthcare professional (AHP) staff had significantly lower mortality rates (1.04, 95%CI 1.02 to 1.06, and 1.04, 95%CI 1.02 to 1.06, respectively), while those with higher support staff had higher mortality rates (0.85, 95%CI 0.79 to 0.91 for nurse support, and 1.00, 95%CI 0.99 to 1.00 for AHP support), after adjusting for multiple staff groups and hospital characteristics. Estimates of staffing levels on mortality were higher in magnitude between- than within-hospitals, which were not statistically significant in a within-between random effects model. ConclusionsWe showed the importance of considering multiple staff groups simultaneously when examining the association between hospital mortality and clinical staffing levels. Despite not being included in previous workforce studies, AHP and AHP support levels have a significant impact on hospital mortality. As the main variation was seen between-as opposed to within-hospitals, structural recruitment and retention difficulties coupled with financial constraints could contribute to the effect of staffing levels on hospital mortality.

BackgroundFormerly incarcerated individuals experience high tuberculosis (TB) incidence rates but are generally not considered among risk groups eligible for TB prevention. We investigated the potential health impact and cost-effectiveness of Mycobacterium tuberculosis (Mtb) infection screening and TB preventive treatment (TPT) for formerly incarcerated individuals in Brazil. MethodsUsing published evidence for Brazil, we constructed a Markov state transition model simulating TB-related health outcomes and costs among formerly incarcerated individuals. The analysis compared TB infection screening and TPT to no screening, considering a combination of Mtb infection tests and TPT regimens. We quantified health effects as reductions in TB cases, TB deaths and disability-adjusted life years (DALYs). We assessed costs from a TB programme perspective. We report intervention cost-effectiveness as the incremental costs per DALY averted, and tested how results changed across subgroups of the target population. FindingsAll TPT interventions were cost-effective in comparison to no screening, with a strategy including a tuberculin skin test and a 3-month isoniazid and rifapentine regimen costing $242 per DALY averted. It was estimated to avert 31 (95% uncertainty interval: 14-56) lifetime TB cases and 4.1 (1.4-8.5) lifetime TB deaths per 1,000 individuals receiving the intervention. Younger age, longer incarceration, and more recent prison release were each associated with significantly greater health benefits and more favorable cost-effectiveness ratios; however, the intervention was cost-effective for all subgroups examined. InterpretationMtb infection screening and TPT appear cost-effective for formerly incarcerated individuals. FundingNIH. Evidence in contextO_ST_ABSEvidence before this studyC_ST_ABSIn many settings, incarcerated individuals have been shown to face higher risks of Mycobacterium tuberculosis (Mtb) infection than the general population. Individuals exiting prison have been found to experience elevated tuberculosis incidence rates over several years, and studies have also reported evidence of elevated tuberculosis incidence in surrounding communities. While several studies have investigated the health impact and cost-effectiveness of interventions to detect and prevent TB disease within prisons, few studies have examined the health impact and cost-effectiveness of interventions to treat Mtb infection among formerly incarcerated individuals. Added value of this studyUsing a Markov model, we simulated lifetime results among a cohort of formerly incarcerated individuals in Brazil offered screening and treatment for Mtb infection. To our knowledge, this is the first study to investigate the health impact and cost-effectiveness of screening and treatment among this cohort. The results contribute to the ongoing efforts to effectively reduce the TB burden and reach the WHOs End TB goals in 2030. Implications of all the available evidenceScreening and treatment of Mtb infection among formerly incarcerated individuals would produce substantial health benefits and be highly cost-effective in the setting examined in this study.

Background Infections have been associated with adverse mental health outcomes, including suicide, but evidence beyond severe or central nervous system infections is limited. We investigated associations between a range of acute infections and subsequent suicide/self-harm outcomes. Methods We conducted six infection-specific matched cohort studies using English primary care records from the Clinical Practice Research Datalink Aurum (2007-2024), linked to hospital admissions and mortality data. Adults ([≥]18 years) with a primary care record of infection (gastroenteritis, lower respiratory tract [LRTI], skin/soft-tissue [SSTI], urinary tract [UTI], sepsis, meningitis/encephalitis [positive control]) were matched (age, sex, practice, calendar period) to up to five comparators without infection. We estimated hazard ratios (HRs) for suicide/self-harm outcomes using Cox regression, stratified by matched set and implicitly adjusting for matching factors, with additional adjustment for deprivation, lifestyle factors, and comorbidities. We examined whether associations varied over time, by infection severity, antimicrobial treatment, sex, and prior mental health conditions. Findings Cohorts ranged from 18,192 individuals with meningitis/encephalitis (matched to 90,915 without) to 398,099 with SSTI (matched to 1,743,747). After adjustment, individuals with infection had a higher hazard of suicide/self-harm outcomes than comparators across all cohorts: sepsis (HR 1.79, 95% CI 1.65-1.93), gastroenteritis (1.62, 1.55-1.70), meningitis/encephalitis (1.56, 1.32-1.84), UTI (1.41, 1.33-1.50), SSTI (1.37, 1.31-1.43), and LRTI (1.37, 1.31-1.44). Risk was highest in the year post-infection, attenuating over time, and was higher among severe infections and those without prior mental health conditions. Interpretation Common acute infections recorded in primary care are associated with increased risk of suicide and self-harm, particularly following severe infections and in the year post-infection. Findings support suicide risk monitoring following acute infection, particularly among individuals without prior mental health conditions, and highlight infection prevention as a potentially modifiable strategy in vulnerable populations. Funding Wellcome and La Caixa. Copyright This work is licensed under a Creative Commons Attribution (CC BY) licence.

BackgroundVietnams disease burden has shifted from communicable, maternal, neonatal, and nutritional (CMNN) causes to non-communicable diseases (NCDs), but the tempo, drivers, and regional positioning of this transition have not been jointly quantified. We characterised Vietnams epidemiological transition 1990-2023 against ten Southeast-Asian (SEA) peers. MethodsUsing Global Burden of Disease 2023 data, we computed joinpoint-regression AAPC with 95% CI (BIC-penalised, up to three break-points) for age-standardised DALY rates and cause-composition shares. We applied Das Gupta three-factor decomposition to 1990-2023 absolute DALY change (population-size, age-structure, age-specific-rate effects) and benchmarked Vietnams NCD share against an SDI-conditional peer trajectory via leave-one-out quadratic regression. Premature mortality was quantified as WHO 30q70 under both broad NCD and strict SDG 3.4.1 definitions, using Chiang II life-table adjustment identically across all eleven countries. FindingsThe CMNN age-standardised DALY rate fell from 13,295.9 to 4,022.1 per 100,000 (AAPC -4.63%/year; 95% CI -4.80 to -4.46); the NCD rate fell only from 21,688.2 to 19,282.8 (AAPC -0.37; -0.45 to -0.30). NCD share of total DALYs rose from 52.99% to 70.67% (+17.67 pp; AAPC +1.09). Vietnam ranked fourth of eleven SEA countries in 2023 (up from sixth in 1990) and sat 5.3% above the SDI-expected trajectory. Das Gupta decomposition attributed the +10.63 million NCD DALY increase to population growth (+6.26 M) and ageing (+6.08 M); rate change removed only 1.71 M. Premature NCD mortality fell from 25.02% to 21.80% (broad, 12.9% reduction) and from 22.17% to 19.50% (SDG 3.4.1, 12.0%; Vietnam sixth of eleven) - far short of the SDG 3.4 one-third-reduction target. InterpretationVietnam has entered a disability- and ageing-dominated NCD phase. Meeting SDG 3.4 by 2030 requires population-scale primary prevention sized to demographic momentum. FundingThis research received no specific grant from any funding agency.

ObjectiveThe purpose of this study was to apply clustering methods to identify and characterize prediabetes phenotypes and their relationships with treatment arm and type 2 diabetes (T2D) outcomes in the Diabetes Prevention Program (DPP), and to compare the utility of additional clustering measures in phenotype characterization and T2D risk stratification. Research Design and MethodsThis was a secondary analysis of data from a subset of participants (n=994) from the previously completed Diabetes Prevention Program trial. Unsupervised k-means clustering analysis was applied to derive the optimal number of clusters of participants based on common clinical risk factors alone or common risk factors plus more comprehensive measures of glucose tolerance and body composition. ResultsFive clusters were derived from common clinical characteristics and the addition of comprehensive measures of glucose tolerance and body composition. Within each modeling approach, participants show significantly different levels of risk factors. The clinical only model showed higher accuracy for time to T2D, however the more comprehensive models further differentiated a metabolically health overweight phenotype. For both models, the greatest differentiation in determining time to T2D was in the metformin arm of the trial. ConclusionsData driven clustering of patients with prediabetes allows for identification of prediabetes phenotypes at greater risk for disease progression and responses to risk reduction interventions. Further investigation into phenotypic differences in treatment response could enable better personalization of prediabetes and T2D prevention and treatment choices.

ImportanceSemaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), is a highly effective medication to treat type 2 diabetes and obesity. However, concerns about potential suicidality persist, creating clinical uncertainty about its neuropsychiatric safety. ObjectiveTo assess risks of suicidality after initiating semaglutide compared to initiating SGLT2i and by duration of continuous semaglutide treatment. DesignActive-comparator, new-user target trial emulation to estimate inverse probability-weighted marginal cause-specific hazard ratios (HRs). For duration-of-treatment analyses, we used clone-censor-weight methods to estimate exposure-adjusted effects. SettingVeterans Health Administration. ParticipantsU.S. Veterans with type 2 diabetes receiving care from March 1, 2018 to September 1, 2025. ExposureInitiation of semaglutide vs SGLT2i; duration of semaglutide use ([&le;]6, 7-12, >12 months). OutcomesIncident suicidal ideation; suicide attempt or death; and a composite outcome. ResultsA total of 102,361 Veterans met inclusion criteria, including 11,478 new initiators of semaglutide and 90,883 new initiators of an SGLT2i. After overlap weighting, baseline characteristics were well balanced between treatment groups (mean [SD] age, 60.1 [11.7] years; BMI, 37.8 [6.8] kg/m2; hemoglobin A1c, 7.0% [1.4]; 85.5% male; 61.9% non-Hispanic White). During a median follow-up of 2.2 years, 9077 incident suicidal ideation events and 696 suicide attempts or deaths occurred. The incidence rate of suicidal ideation was 56.3 and 37.7 per 1000 person-years among semaglutide initiators and SGLT2i initiators, respectively (hazard ratio [HR], 0.99; 95% CI, 0.93-1.06; P = 0.86). For suicide attempts or deaths, the incidence rates were 4.30 and 2.64 per 1000 person-years, respectively (HR, 1.05; 95% CI, 0.84-1.31; P = .86). In adherence-adjusted analyses, sustained semaglutide treatment for more than 12 months, compared with 6 or fewer months, was associated with a 74% lower risk of suicide attempts or deaths (HR, 0.27; 95% CI, 0.14-0.54; P<.001). ConclusionAmong U.S. Veterans with type 2 diabetes, initiators of semaglutide were not observed to have an increased risk of suicidality compared with initiators of SGLT2i. Those with longer semaglutide treatment (beyond 12 months) had decreased risk of suicide attempt or death, suggesting longer term treatment is safe and may protect against for those outcomes.

BackgroundConcurrent maternal-child double burden of malnutrition (DBM) affects a growing share of mother-child dyads in low- and middle-income countries (LMICs). Nutrition programmes often use maternal education as an eligibility proxy, but whether algorithmic alternatives would do better--and at what equity cost--has not been directly tested. We evaluated whether machine learning (ML)-based targeting for two concurrent DBM subtypes--overweight mother with stunted or wasted child (Subtype A) and underweight mother with stunted or wasted child (Subtype B)--improves recall over a proxy-based rule while preserving fairness across social strata. MethodsWe pooled Phase 7-8 Demographic and Health Surveys from 30 LMICs (181,636 mother-child dyads). We first estimated subtype-specific social gradients with multilevel logistic regression. We then trained xgboost prediction models with strict label-leakage safeguards and leave-one-country-out cross-validation, and compared ML-based targeting against random and education-based rules at 10%, 20%, and 30% budget constraints. Fairness was audited along six social strata using equalized-odds, demographic-parity, calibration, and predictive-value gaps. A full-India sensitivity analysis (354,691 dyads) assessed robustness to down-sampling. FindingsOverall weighted any-DBM prevalence was 12.52% (Subtype A: 8.21%; Subtype B: 4.31%). Subtype A showed an inverted-U gradient on wealth (adjusted odds ratio peak 1.22 at Richer versus Poorest) and maternal education (peak 1.23 at Primary versus None); Subtype B declined monotonically (wealth: 0.25 at Richest; higher education: 0.49). Mean leave-one-country-out area under the curve was 0.615 for Subtype A and 0.652 for Subtype B. At a 20% budget, ML captured 35.3% of Subtype A cases versus 18.4% for education-based targeting (+92%); for Subtype B the corresponding values were 37.5% and 32.1% (+17%). Equalized-odds gaps reached 0.57 on country income and 0.59 on maternal education; true-positive rates were lowest in the highest-wealth and highest-education strata. Results were stable under the full-India sensitivity analysis. ConclusionsML is useful principally for Subtype A, where the education proxy is no better than random. For Subtype B it mostly changes who gets reached rather than how many, which is a policy choice rather than an accuracy upgrade. The households the algorithm most often misses are not the poor but the rare positives in high-resource strata, which is what a fixed-budget rule ranking on heterogeneous base rates will do. Programmes should decide whether their priority is total capture or the distribution of capture before adopting such a rule. Author SummaryIn many low- and middle-income countries, mothers who are overweight often live in the same household as children who are too short or too thin for their age. Nutrition programmes that try to reach such families have limited resources, so they must choose which households to prioritise. Most programmes use maternal education level as a rough filter, but whether this is actually a good way to find affected families has rarely been tested. We used surveys of 181,636 mother-child pairs from 30 low- and middle-income countries to compare three ways of identifying at-risk households: random selection, selection by low maternal education, and selection by a machine-learning model. Machine learning was much better at finding families where an overweight mother lives with an undernourished child--nearly doubling the capture rate compared with the education rule. For a different combination (underweight mother with an undernourished child), machine learning did not clearly outperform education on total recall; instead it reached different households, mostly shifting attention toward the rural poor. An unexpected finding was that the households the algorithm was most likely to miss were not the poor ones, but the wealthier and better-educated ones, where this type of malnutrition is rarer. This is not bias against the poor--it is what happens when any ranking rule operates under a fixed budget. Programmes that want to reach everyone at risk, regardless of how rare risk is in a given group, may need more than one rule.

BackgroundSouth Africa accounts for 20% of the global HIV infections and has one of the highest HIV incidence rates in the world. Six-monthly injectable lenacapavir (LEN) for HIV pre-exposure prophylaxis (PrEP) has superior efficacy to oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), and similar efficacy to 2-monthly injectable cabotegravir (CAB). With LENs recent regulatory approval and the newly negotiated generic price of $40 per person per year, South Africa faces critical implementation decisions amid constrained domestic resources and reduced international funding. We evaluated the epidemiological impact on HIV infections and life years lost, cost-effectiveness, and optimal populations for LEN roll-out in South Africa. Methods and FindingsUsing Thembisa v4.8, a deterministic compartmental HIV transmission model of the South African HIV epidemic, we simulated the impact of LEN scale-up, expanded oral TDF/FTC, and CAB scale-up, compared to a baseline of current TDF/FTC provision over 20 years (2026-2045). We scaled PrEP among adolescent girls and young women (AGYW), female sex workers (FSW), pregnant and breastfeeding women (PBFW), men who have sex with men (MSM), and heterosexual men. For TDF/FTC scale-up, we doubled baseline initiation rates. For LEN and CAB, conservative and optimistic scenarios assumed initiation rates similar to or double those under TDF/FTC scale-up, respectively. Duration of use varied by subpopulation under TDF/FTC (3-6 months), conservative (LEN: 6-12 months, CAB: 4-8 months), and optimistic (LEN: 12-24 months, CAB: 8-16 months). We modelled strategies to maximise the impact of ~500,000 LEN doses currently allocated for 2026-2027, or large-scale roll-out. Costs are presented from the South African governments perspective in undiscounted 2025 USD. Providing LEN to 1.7-2.9 million South Africans per year averted 19-31% of infections and saved 3-5% of life years anticipated to be lost to HIV, reaching incidence <0.1% in 2039-2043, 10-14 years earlier than baseline. Estimating the number of individuals needed to initiate each PrEP type to avert one HIV infection, LEN required 35-65 initiations/infection averted, compared to CAB (45-125 initiations/infection averted) and TDF/FTC (280 initiations/infection averted). TDF/FTC and conservative LEN scale-up increased HIV programme costs by 3%; however, LEN was more cost-effective, costing $2,301-$3,567/life year saved (LYS) versus $8,143/LYS (TDF/FTC scale-up) and $11,114-$16,118/LYS (CAB). Prioritising PBFW, MSM, and FSW for the initial allocation maximized infections averted. Large-scale roll-out strategies prioritizing FSW and MSM were most cost-effective ($276-$958/LYS). Limitations to this study include uncertainty in achieving modelled uptake and assumptions of risk-differentiated uptake of long-acting products, and limited data on real-world implementation costs. InterpretationDelivering LEN to persons with elevated HIV risk in South Africa is more cost-effective than existing PrEP options and can speed up HIV incidence reduction. Prioritising uptake among groups at highest risk is essential to maximise impact and cost-effectiveness.

BackgroundHypertension is a major cause of morbidity and mortality worldwide. Previous efforts to characterize gaps in the hypertension care continuum in India -including diagnosis, treatment, and control- did not assess district level variation. Local data are critical for planning, implementation, and monitoring efforts to curb hypertension burdens. Our objective is to characterize the hypertension care continuum in India among individuals aged 18-98 years old at national, state, and district levels and by socio-demographic group. MethodsData were from 1,895,297 individuals in the nationally representative Fifth National Family Health Survey (NFHS-5), 2019-21. Hypertension was defined as self-reported diagnosis or newly measured blood pressure [&ge;]140/90 mmHg. Among those with hypertension, we calculated the proportion diagnosed (self-reported). Among those with diagnosed hypertension, we computed the proportion treated (self-reported medication use). Among those treated, we calculated the proportion controlled (BP <140/90 mmHg [20-80 years] or <150/90 mmHg [>80 years]) based on national guidelines. Estimates were also provided among the total with hypertension. To assess differences in the care continuum between or within states (i.e. between districts), we partitioned the variance at both levels using linear mixed models. ResultsAmong 1,691,109 adult respondents nationally (52.6% female; mean age: 41.6 years), 28.2% [95%CI: 28.0-28.4] had hypertension, of whom, 36.7% [36.3-37.2] were diagnosed. Among those diagnosed, 44.7% [44.1-45.3] reported taking medication (17.7% [17.5-17.9] of total with hypertension). Among those treated, 52.3% [51.4-53.1] had blood pressure control (9.1% [8.9-9.2] of total with hypertension). There were substantial variations across districts in diagnosis [range: 6.3-77.5%], treatment [8.7-97.1%] and control [2.7-76.6%]. Notably, large proportions of the variation in hypertension diagnosis (53.7%), treatment (32.8%), and control (57.7%) were within states, not just between states. ConclusionsIn India, more than 1 in 4 people have hypertension, and of these, only 1 in 3 are diagnosed, less than 1 in 5 are treated, and only 1 in 11 controlled. National averages hide considerable state- and district-level variation in the care continuum, implying the need for targeted, decentralized solutions to improve the hypertension care continuum in India.

BackgroundCardiovascular diseases (CVDs) are the leading cause of death in most low- and middle-income countries (LMICs). CVDs and their metabolic risk factors have historically been concentrated among urban residents with higher socioeconomic status (SES) in LMICs such as India. However, as India develops, it is unclear whether these socioeconomic and geographic gradients will persist or change. Understanding these social dynamics in CVD risk is essential for mitigating the rising burden of CVDs and to reach those with the greatest needs. MethodsUsing nationally representative data with biomarker measurements from the fourth (2015-16) and fifth (2019-21) Indian National Family and Health Surveys, we investigated trends in the prevalence of four CVD risk factors: tobacco consumption (self-reported, any type), unhealthy weight [Formula], idiabetes (random plasma glucose concentration [&ge;]200mg/dL or self-reported diabetes), and hypertension (one of: average systolic blood pressure [&ge;] 140mmHg, average diastolic blood pressure [&ge;] 90mmHg, self-reported past diagnosis, or self-reported current antihypertensive medication use) among adults aged 15-49 years. We first described changes at the national level and then trends stratified by place of residence (urban versus rural), geographic region (northern, northeastern, central, eastern, western, southern), regional level of development (Empowered Action Group member state or not), and two measures of socioeconomic status: level of education (no education, primary incomplete, primary complete, secondary incomplete, secondary complete, higher) and wealth (quintiles). FindingsUnhealthy weight increased among all social and geographic groups but both the absolute and the relative changes were substantially higher among people with low SES (as measured by education or wealth) and in rural areas. For diabetes and hypertension, the prevalence increased for those from disadvantaged groups while staying constant or even decreasing among the wealthier and more educated. In contrast, tobacco consumption declined for all social and geographic groups. InterpretationIn 2015-16, CVD risk factors were higher among more advantaged subpopulations in India. However, between 2015-16 and 2019-21, the prevalence of these risk factors grew more rapidly for less wealthy and less educated subpopulations and those living in rural areas. These trends have resulted in CVD risk becoming far more widespread throughout the population; CVD can no longer be characterized as a wealthy urban phenomenon. FundingThis work was supported by the Alexander von Humboldt Foundation [NS]; the Stanford Diabetes Research Center [PG], and the Chan Zuckerberg Biohub [PG]. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for work published between Jan 1, 1990, and Sep 23, 2022, with variations of the search terms "reversal hypothesis", "social gradient", "socioeconomic gradient", "social difference", "socioeconomic difference", "socioeconomic status", "change", "trend", "cardiovascular disease", "cardiovascular risk factor", "diabetes", "hypertension", "overweight", "obesity", "smoking", "tobacco", "low-income", "lower-middle-income", and "India" in the title or abstract. Existing studies on changes in the socioeconomic patterning of cardiovascular disease (CVD) risk factors mostly compared the size of social gradients in obesity cross-sectionally between countries at different levels of national income or development. These studies generally found higher obesity among higher socioeconomic status (SES) populations but opposite gradients for countries at higher levels of development. However, because these studies use cross-sectional comparisons, whether these patterns reflect the influence of development or other contextual factors associated with countries at different levels of development is unclear. Both for obesity and for other CVD risk factors, we found few nationally-representative studies that traced how gradients within countries changed over time as they developed. Importantly, most of these studies did not focus on India and those that did only considered single risk factors such as obesity using older data. Existing nationally representative research on India is thus predominantly cross-sectional and has only focused on the size of social gradients at single points in time. This work generally finds higher levels of unhealthy weight, diabetes, and hypertension among wealthy and educated subpopulations but lower levels of tobacco consumption. Subnational and smaller non-representative studies from India that traced changes in CVD risk factors over time provide some evidence of reversing or flattening gradients but it is unclear whether these patterns hold at regional and national levels. Added value of this studyUsing data from the 2015-16 and 2019-2021 National Family and Health Surveys, we provide some of the first nationally representative evidence for trends in the prevalence of major CVD risk factors in India and how these trends have changed across social and geographic groups. Both absolute and relative increases in prevalence were far more pronounced among relatively poor and less educated populations. As a result of these trends, most CVD risk factors became more equal across population groups, or in some cases, became higher among the less compared to more educated. Implications of all the available evidenceIndians with lower SES - as measured by wealth and education - experienced considerable adverse trends in unhealthy weight, diabetes, and hypertension between 2015-16 and 2019-21. Our results reveal that CVDs can no longer be considered a problem of the affluent parts of society and suggest that CVD prevention efforts that reach less advantaged subpopulations are urgently needed.

BackgroundThe multicentre WOMAN trial showed that tranexamic acid reduces postpartum haemorrhage (PPH) deaths. Several studies have recommended adjusting for clustering at the country and centre level to improve power and reduce bias in the standard errors. We reanalysed data from the WOMAN trial, adjusting for these centre effects. MethodsThe WOMAN trial recruited 20,060 women with clinically diagnosed PPH from 193 centres in 21 countries. The intervention was intravenous tranexamic acid versus matching placebo and the outcome was death from bleeding within 42 days of randomisation. We reanalysed data for the 14,928 women treated within 3 hours of birth for whom tranexamic acid provided the most benefit. We used random effects logistic regression to calculate the effect of tranexamic acid taking into account variation in risk of death and treatment effectiveness by country and centre. We calculated intraclass correlations (ICCs) to quantify between country and between centre within country variation. Results216 (1.4%) women died from bleeding. Using a univariable analysis without adjusting for centre effects, we found tranexamic acid reduced the odds of death from bleeding by 31% (OR=0.69 95% CI: 0.52-0.90, p=0.007). Adjusting for baseline covariates (age, systolic blood pressure (SBP) and SBP2) but not country or centre yielded a 36% odds reduction (OR=0.64 95% CI: 0.48-0.85 p=0.002). Adjustment for baseline covariates, country and centre yielded a 37% odds reduction (OR=0.63 95% CI: 0.48-0.85 p=0.002). We found substantial between country and centre variation in outcomes but not treatment effectiveness. The ICC for outcome was 14% for country and 19% for centre within country. ConclusionsAdjusting for country and centre effects made negligible differences to the magnitude of the treatment effect estimate or its associated p-value. Consistent with other studies of large clinical trials for medicines with binary outcomes, we found considerable between country and centre variation in outcomes but not in relative treatment effectiveness. Despite substantial ICCs for the outcome, adjusting for country and centre effects had minimal impact on our results. Trial registrationclinicalTrials.gov:NCT00872469 (March 2009)

Potassium-containing low-sodium salt substitutes (LSSS) may lower sodium intake, increase potassium intake, and reduce cardiovascular risk in mixed adult populations, but the review literature is overlapping and methodologically heterogeneous. This umbrella review assessed the efficacy, safety, and evidence quality of potassium-containing LSSS for blood pressure, cardiovascular outcomes, and adverse events. Following a registered PROSPERO protocol (CRD420261294404), we searched PubMed, Embase, Web of Science, Global Health (EBSCO) and the Cochrane Database of Systematic Reviews from inception to 6 March 2026 for systematic reviews, meta-analyses and umbrella reviews of potassium-containing LSSS. Eleven reviews met eligibility criteria. Methodological confidence was high in one review, moderate in three, low in five and critically low in two. Primary-study overlap was very high (corrected covered area 28.5%). Review-level pooled estimates consistently favoured potassium-containing LSSS for systolic blood pressure (mean differences -4.61 to -8.87 mmHg) and diastolic blood pressure (-1.42 to -4.04 mmHg). Later reviews also reported lower all-cause mortality (RR 0.88-0.89), cardiovascular mortality (RR 0.72-0.87), composite cardiovascular events and selected stroke outcomes; however, clinical-outcome estimates were heavily influenced by the Salt Substitute and Stroke Study. Serum potassium changed minimally (-0.02 to 0.18 mmol/l), and pooled estimates for hyperkalaemia and serious adverse events showed no clear excess risk in trial populations that largely excluded participants at higher risk of impaired potassium handling. Potassium-containing LSSS consistently lower blood pressure and may improve cardiovascular outcomes, but further trials are needed outside Eastern Asia, with clearer formulation reporting, prespecified baseline CVD-history strata, and stronger safety data in higher-risk populations.

BackgroundHypertension (HTN) constitutes a major and growing public health challenge in South Africa, a setting where HIV prevalence also remains high. Despite this dual burden, longitudinal evidence describing how individuals move through the HTN care cascade particularly comparing people living with HIV (PLHIV) and people not living with HIV (PNLHIV) remains limited. Understanding patterns of progression and regression across the cascade is essential to inform health system strategies for integrated chronic disease management. Methods and FindingsWe conducted a longitudinal secondary analysis using data collected from the iHEART-SA trial, which was implemented across nine public primary healthcare clinics in Johannesburg between August 2022 and May 2024. with follow-up through May 2025. Adults ([&ge;]18 years) with a known HIV status and a completed medical file review were included. Progression and regression were assessed across the HTN care cascade. Of 23 855 participants, 78.5% were PLHIV (median age 42 years, IQR 36-49; 69% female). Overall, 34.4% had high blood pressure (BP), with prevalence higher among PNLHIV than PLHIV (53.5% vs 29.3%; p<0.001). Along the HTN care cascade, PLHIV were substantially more likely to remain undiagnosed compared with PNLHIV (aRR 3.40; 95% CI 3.12-3.71). Among those treated, PLHIV were less likely to achieve BP control (aRR 0.83; 95% CI 0.75-0.91). During follow-up, PLHIV experienced higher rates of cascade regression, including regression to untreated HTN (29% vs 19%; aRR 1.51; 95% CI 1.35-1.70) and from controlled to uncontrolled BP (aRR 1.12; 95% CI 1.05-1.18). ConclusionsDespite frequent health-system contact, PLHIV had lower HTN diagnosis and higher regression, including treatment discontinuation and loss of BP control, underscoring persistent gaps in longitudinal HTN management within HIV programmes and the need for integrated and targeted chronic care models that ensure treatment continuity and sustained control.

Abstract Background Tuberculosis (TB) kills 1.3 million people annually. Global efforts focus on ending pulmonary TB (PTB); however, extrapulmonary TB (EPTB) is rising and poses significant health and economic burden. The PreVenTB Phase III trial evaluated VPM1002 in household contacts aged [&ge;]6 years across India, and did not meet its primary composite endpoint for all TB. Disaggregated prespecified secondary endpoints revealed a substantially stronger EPTB signal (vaccine efficacy 42.3%, 95% CI (-9.1 to 69.4, p=0.09) in the modified intention-to-treat (mITT) population. No existing TB model translates these disaggregated hazard ratios into population-level effectiveness across heterogeneous demographics, or against a dynamic baseline accounting for ongoing National Tuberculosis Elimination Programme (NTEP)-driven incidence decline. Methods We developed a 1,296-compartment deterministic dynamic compartmental model (4 age x 2 HIV x 3 BMI x 3 socioeconomic strata x 18 states). Separate PTB and EPTB vaccine-efficacy posteriors were derived by Bayesian evidence synthesis of the PreVenTB trial's per-protocol and mITT analyses (power-prior-adjusted conjugate normal-normal update; =0.082) and propagated through Monte Carlo simulation (n=1,000 iterations per scenario). A dynamic no-vaccine baseline was constructed by fitting time-varying case-detection-rate CDR(t) and treatment-success-rate TSR(t) logistic curves to WHO/NTEP data (2015 to 2024; incidence validation R2=0.896, RMSE 4.90 per 100,000), projecting PTB and EPTB incidence to 2050. Economic analysis used societal (value-of-statistical-life-inclusive BCR) and health-system (cost-effectiveness acceptability curves) perspectives, discounted at 3% annually. Findings Posterior vaccine effectiveness was substantially higher against EPTB than PTB (EPTB 40.0% [95% CI -5.6 to 69.1%] vs PTB 12.8% [-19.0 to 37.9%]; all-TB 16.2% [-11.7 to 38.6%]). EPTB accounted for 74% of deaths averted (381 of 513) and 73% of DALYs averted (5,347 of 7,308) in the 10-year/dynamic scenario. EPTB cases averted exceeded PTB and concurrent disease combined in every scenario. Mean cases averted ranged from 2,047 (3-year protection, dynamic baseline) to 3,394 (10-year, static) per 1,000,000 vaccinated; mean disability-adjusted life years (DALYs) averted ranged from 4,792 to 8,125. The benefit-cost ratio (BCR; societal perspective) ranged from 3.4 (3-year protection, dynamic baseline) to 8.2 (10-year protection, static baseline), exceeding break-even in every scenario. Median gross incremental cost-effectiveness ratio (ICER) ranged from US$647 (10-year static) to US$1,568 (3-year dynamic) per DALY averted, below India's 3x gross domestic product (GDP)-per-capita threshold (approximately US$8,084) in every scenario. Interpretation This 1,296-compartment model provides the first dynamically-baselined, dual-perspective health-economic evaluation of VPM1002 to separately track pulmonary and extrapulmonary outcomes. EPTB protection is VPM1002's proportionally larger and more statistically reliable efficacy signal and drives a majority of averted cases, mortality, and DALYs. Policy assessments anchored to composite pulmonary endpoints systematically underestimate this vaccine's population value. Funding In part funded by Serum Life Science Europe GmbH.

Objective To estimate the potential health and equity impacts of a tobacco free generation (TFG) and T21 policy (increasing the legal age of sale to 21) in Australia, in the context of a complex market including widespread illicit tobacco and e-cigarette product availability. Design A Markov macrosimulation model, parameterised with yearly net movements between legal smoking, illicit smoking, vaping, and dual use states, combined with a proportional multi-state lifetable. Setting The Australian population, modelled as an open cohort for 40-years. Intervention A 'business-as-usual' (BAU) scenario was compared to TFG and T21 policies, with both starting in 2026. Variations to policy impacts were tested under increasing background illicit market enforcement. Main outcome measures The model estimates the health-adjusted life years (HALYs) and deaths over 40 years, under each scenario, with differences across age and socioeconomic status (SES) presented. Results The TFG policy reduced daily smoking prevalence among 15-24-year-olds to 4.6% (95% uncertainty interval [UI] 3.8-5.7%) in 20 years' time, compared to 7.2% under the T21 policy and 7.9% under BAU trends. Vaping was minimally impacted by either policy. The TFG policy resulted in 178,000 (95% UI 87,800-314,000) HALYs being gained over 40 years. The policy impact was largest when accompanied by increased illicit market enforcement, reducing daily smoking among 15-24-year-olds to 1.4% within 20 years. Both policies had greater prevalence and health impacts on more disadvantaged compared to advantaged SES groups. Conclusion A TFG policy is expected to produce long-term benefits for the Australian population but would be most effective in combination with increased enforcement of illicit tobacco and e-cigarette markets. Novel strategies to increase quitting in addition to reducing uptake are needed to improve tobacco-related outcomes in the short to medium term.

BackgroundOf the hundreds of millions of COVID-19 cases globally, most have been non-fatal, though "Long COVID" after acute infection has been documented in many. While many studies have reported post-COVID increases chronic disease incidence including hypertension (HTN), racial/ethnic minority study participants are underrepresented and studies often lacks controls for potential confounds. MethodsWe conducted a case-control cohort time-to-event study of 39,746 individuals incarcerated in 31 California state prisons. The main outcome was incident diagnosed HTN among individuals incarcerated continuously since January 1, 2019 with no HTN diagnosis prior to March 1, 2020 (beginning of the unexposed period of observation). The main exposure was a positive COVID-19 test, with the exposure period beginning 31 days afterwards (post-acute period). Covariates included age, gender, race/ethnicity, BMI, and blood pressure at the pandemics start, frequency of healthcare contacts prior to the pandemic, and COVID-19 testing frequency prior to testing positive. We excluded individuals who lacked BMI or blood pressure measurements prior to or during the pandemic or were never tested for COVID-19 along with those who had been prescribed blood pressure-altering medications. We estimated multivariate Cox proportional hazard models: 1) exposure variable and covariates; 2) adding interactions between the exposure and each covariate. We assessed whether confounding due to changes in HTN testing post-COVID could explain our results. ResultsCOVID-19 infection significantly increased the rate of incident HTN (main effects model HRR: 1.44 [95%CI: 1.32-1.57]; including interactions HRR: 2.05 [1.50-2.79]). If all individuals in our study had a COVID-19 infection, the 2-year cumulative risk of hypertension was 7.1% [5.7%-8.5%] versus 5.0% [4.2%-5.9%] if none had been infected. The largest absolute effects of COVID-19 on HTN incidence were in those with higher BMIs, higher pre-pandemic blood pressure levels and older ages. Our findings remained consistent with different definitions of the post-acute period and to confounding due to changes in HTN testing post-COVID. ConclusionCOVID-19 increases the risk of incident hypertension long after acute infection. As so many people have had COVID-19 and elevated blood pressure, additional provider awareness and clinical consideration are warranted.

IntroductionReliable estimates of resource requirements for essential health interventions are critical for universal health coverage (UHC) planning. Existing benchmarks provide limited operational guidance for national decision-making. MethodsWe developed an ingredient-based costing model aligned with the WHO Universal Health Coverage Compendium (UHCC), which specifies delivery platforms, actions and technologies for 544 interventions. We estimated resource needs and costs associated with delivery of all UHCC-defined interventions at 80% coverage across 122 low- and middle-income countries, applying a multimorbidity adjustment to reduce potential double counting and using authoritative epidemiological, demographic and cost data. ResultsModeled delivery of Core UHCC interventions is estimated at USD 2.0 trillion annually (5.7% of aggregate gross domestic product) or USD$249, 294 and 363 per capita in low-, lower-middle- and upper-middle-income countries, respectively. Cost estimates closely aligned with WHO projections for achieving Sustainable Development Goal 3, but were 1.7-2.7x higher than Disease Control Priorities Network internal cost estimates. ConclusionThe UHCC aligned cost model provides transparent resource need and cost data under normative service delivery assumptions, and offers a practical starting point for country-level contextualization for health service packages planning.

BackgroundMarked declines in pediatric HIV have been achieved across sub-Saharan Africa, yet progress among adolescents remains uneven and strongly patterned by place. Drawing on place-based perspectives in health geography, we conceptualize Eastern and Southern Africa (ESA) and West and Central Africa (WCA) not merely as epidemiological regions, but as dis-tinct assemblages of health systems, gender norms, and historical investment trajectories shaping HIV risk and care. Using UNICEF-harmonized indica-tors from 2000 to 2024, we examined how place structures progress toward the 2030 Sustainable Development Goal (SDG 3.3) target. MethodsWe pooled country-level estimates using inverse-variance random-effects meta-analysis (restricted maximum likelihood for{tau} 2 with Hartung-Knapp adjustment). HIV incidence and AIDS-related mortality were analysed on the log scale, and mother-to-child transmission (MTCT) on the logit scale. Outcomes were pooled by region, age group (0-14; 15-19), sex, and year. We quantified percentage change from 2010 to 2024, the achieved annualized rate of change (ARC), and the required ARC from 2024 to 2030 to achieve a 90% reduction from 2010 levels. Robustness was assessed using prespecified sensitivity analyses. FindingsBetween 2010 and 2024, child HIV incidence declined by 72% in ESA and 66% in WCA, while adolescent incidence declined by 54% and 62%, respectively. In 2024, MTCT remained above elimination thresholds in both regions (9.9% in ESA; 17.6% in WCA). Adolescent girls experienced substantially higher HIV incidence than boys, with pooled female-to-male incidence rate ratios of 4.13 (95% CI: 3.32-5.13) in ESA and 4.92 (4.04-5.99) in WCA. Despite progress, achieved declines among adolescents (ARC: -5.4%/year in ESA; -6.6%/year in WCA) fall well short of the acceleration required to meet 2030 targets. ConclusionHIV progress among children and adolescents in sub-Saharan Africa is deeply place-dependent. While ESA reflects the benefits of earlier and sustained health system investments, persistent structural and gendered vulnerabilities continue to constrain adolescent outcomes, particularly in WCA. Achieving SDG 3.3 will require place-responsive strategies that integrate gender-sensitive adolescent prevention, differentiated care, and strengthened PMTCT within the specific social, political, and health system contexts shaping risk and access. HighlightsO_LIHIV declines among children and adolescents show strong place-based patterning. C_LIO_LIChild HIV incidence declined faster in ESA than in WCA, 2010-2024. C_LIO_LIAdolescent girls had four- to five-fold higher HIV incidence than boys. C_LIO_LIMTCT remains above elimination thresholds, especially in West and Central Africa. C_LIO_LIMeeting 2030 targets requires accelerated, place-responsive strategies. C_LI

Background: Suicide is the second leading cause of death in US adolescents aged 10-24. Method use strongly influences lethality and design of prevention strategies, but recent trends remain unclear. We therefore aimed to investigate trends in suicide mortality rates by method, age group, and sex. Methods: This cross-sectional study used suicide mortality data from the National Center for Health Statistics for a quarter-century period, between 1999 and 2024. All individuals aged 10-24 years at the time of death, with suicide as the underlying cause, were included. We estimated suicide mortality rates (i.e., the number of suicide deaths per 100,000 people) and annual percent change by method (firearm, asphyxiation, poisoning, other), age group (10-14, 15-19, 20-24), and sex. Changing trend time points were determined using Joinpoint regression models Results: From 1999 to 2024, 159,241 suicide deaths occurred among individuals aged 10-24. While suicide rates declined across all age groups between 2017 and 2024, the male-to-female gap narrowed by 18.9%. Among 10-14-year-olds, declining rates among males masked a consistent increase in female suicide rates since 2011. Although asphyxiation-related suicides decreased across all groups since 2018, firearm suicide rates increased for females in the 10-14 and 20-24 age groups. Albeit not as common as firearms or asphyxiation, poisoning suicide rates increased in the 15-19 and 20-24 age groups. Since 1999, suicide rates by other less common methods (e.g., jumping) showed significant increases, for both sexes, especially among individuals aged 20-24. Suicide rates were consistently highest in the 20-24 age group across all study years. Conclusion: The decrease in suicide mortality rates among individuals aged 10-24 was largely driven by declines in males and reductions in asphyxiation-related suicides. However, increasing female suicide rates in the 10-14 age group, as well as increasing rates of death by less common means, warrant close attention. While suicide prevention efforts like structural interventions and means restriction have shown effectiveness among male adolescents, priority should now be given to adapting these approaches for female adolescents, particularly those aged 10-14.

BackgroundDeath certificates record both an underlying cause and contributing conditions, yet mortality statistics predominantly report only the underlying cause. We quantify this "hidden burden" across all ICD-10 conditions in Australian mortality data using the multiple-to-underlying ratio (MUR): total death certificate mentions divided by underlying cause deaths. MethodsWe analysed Australian Bureau of Statistics Causes of Death 2023 data (N = 187,268 registered deaths) to compute the ratio for all ICD-10 conditions. Three pre-registered confirmatory hypotheses tested sex differences in hypertension and mental health ratios, and geographic variation by preventability, with Holm-Bonferroni correction. ResultsDeath certificates recorded an average of 3.5 causes per decedent, meaning the underlying cause captures only [~]29% of recorded morbidity. Of 663 conditions with [&ge;]10 underlying cause deaths, the ratio ranged from 1.0 (external causes) to 281.1, with a median of 2.5. Among conditions with stable estimates ([&ge;]50 underlying deaths), the highest ratio was 94.3 (complications of medical care). Age explained only 10.9% of ratio variation (R2 = 0.109), and no top-ranked conditions were identified as primarily age-driven, suggesting the ratio ranking is robust to age confounding. However, external validation using US CDC data showed age standardisation materially changed absolute ratio values for 6 of 8 cause groups (divergence 16-34%), with the direction varying by condition rather than following a simple age-concentration pattern. Males showed consistently higher ratios, most strikingly for mental health disorders (62% higher); a counterfactual analysis estimated suicide coding rules explain only 6-15% of this sex difference. Three pre-registered hypotheses were null after correction; H1 and H3 (sex differences) were underpowered (n = 4, n = 8 pairs) with large effect sizes (r = 0.77-0.80), while H2 (geographic variation) showed a clear null. ConclusionsThe hidden burden of mortality in Australia is substantial and unevenly distributed, with symptom codes, mental health conditions, and hypertension most undercounted. The ratio provides a transparent framework for identifying conditions whose health impact is systematically understated by conventional mortality reporting.