BACKGROUND: Postnatal care (PNC) plays a crucial role in averting newborn mortality, yet its use remains low, particularly in regions with the highest mortality. While demographic and social determinants of PNC use have...BACKGROUND: Postnatal care (PNC) plays a crucial role in averting newborn mortality, yet its use remains low, particularly in regions with the highest mortality. While demographic and social determinants of PNC use have been well studied and have informed current strategies focused on changing care-seeking behaviors, the stagnating decline in neonatal mortality highlights the need for upstream and system-wide approaches to increase PNC uptake. Limited evidence exists to guide system-level reforms; therefore, we investigated whether health systems that ensure high-quality perinatal care are associated with increased use of PNC. METHODS AND FINDINGS: We performed a cross-sectional observational study using Demographic and Health Survey data from 38 countries that had not met SDG neonatal mortality targets by 2020. The study population comprised women aged 15-49 years whose most recent live birth occurred within five years preceding the survey. We employed logistic regression models with country fixed effects to examine associations between: (1) perinatal service utilization, (2) service quality; and their relationship with postnatal checkups for newborns within 28 days. We analyzed utilization-quality interactions to determine how the effects of service coverage on PNC use varied by care quality and conducted wealth-stratified analyses to assess how quality effects on PNC use differed across socioeconomic groups. High-quality perinatal care was associated with a 2-fold increase in the probability of postnatal checkups within 28 days (0.406 in the highest quality tertile versus 0.221 in the lowest quality tertile). For mothers who received the lowest tertile of service quality, full utilization of perinatal services yielded negligible changes in postnatal checkup probability (0.217 to 0.216). Conversely, for mothers who received the highest quality of antenatal and perinatal care, full access to perinatal care improved the probability of postnatal check-ups (0.392 to 0.428). Notably, women in the lowest wealth quintile experienced a substantial increase in postnatal checkup probability from 0.224 to 0.481 between low and high-quality care cohorts, while this differential was less pronounced in the highest wealth quintile (0.236 to 0.450). Key limitations include restricted quality indicators, potential recall bias from self-reported measures, limited information on follow-up care, and the cross-sectional nature of the data, which limits causal interpretation. CONCLUSIONS: Our interaction analysis reveals a critical insight: high-quality care substantially enhanced the magnitude of the association between expanded perinatal service use and PNC use, whereas increased utilization alone was not linked to higher PNC uptake. Notably, the impact of improved care quality was most pronounced among the lowest wealth groups, highlighting its potential as a mechanism for promoting equity. By demonstrating the central role of care quality in promoting PNC utilization, particularly among disadvantaged populations, our findings suggest that improving health system quality could be a more effective strategy for achieving universal maternal healthcare coverage than traditional access-focused approaches.
BACKGROUND: Treatment-resistant depression (TRD), defined as failure to respond to at least two adequately administered antidepressant (AD) regimens, imposes major clinical and economic burdens. Esketamine nasal spray of...BACKGROUND: Treatment-resistant depression (TRD), defined as failure to respond to at least two adequately administered antidepressant (AD) regimens, imposes major clinical and economic burdens. Esketamine nasal spray offers rapid antidepressant clinical effects, yet previous evaluations compared it only with unrealistic comparators such as AD monotherapy. This study assessed the cost-effectiveness of esketamine versus multiple alternative third-line strategies for TRD from the Hong Kong healthcare payer's perspective. METHODS AND FINDINGS: A Markov cohort model simulated adults with TRD in Hong Kong over 5 years with 4-week cycles. The model compared esketamine plus AD with six alternative third-line treatment strategies: combination therapy (AD plus AD), augmentation therapy (AD plus antipsychotic or lithium), psychotherapy alone, psychotherapy plus AD, repetitive transcranial magnetic stimulation (rTMS) plus AD, and electroconvulsive therapy (ECT) plus AD. Primary outcomes were quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) under a US$50,000/QALY willingness-to-pay (WTP) threshold. Deterministic and probabilistic sensitivity analyses and scenario analyses were conducted, focusing on alternative esketamine dosing, delivery strategies, and comparisons with other treatment options to assess the robustness of the results. In base-case analysis, esketamine was not cost-effective versus augmentation, combination, psychotherapy, or psychotherapy plus AD with ICERs ranging from US$134,127 to US$312,750 per QALY but was more cost-effective than rTMS (dominated) and ECT (ICER: US$322,407/QALY). Combination therapy was the most cost-effective among all strategies evaluated. The main limitation of this study is the reliance on indirect comparisons and assumptions derived from heterogeneous clinical trial populations, which may not fully reflect real-world patient characteristics and treatment pathways. CONCLUSIONS: Esketamine appeared more cost-effective than rTMS and ECT, but not cost-effective compared with other commonly used third-line treatment strategies for TRD. These findings suggest that cost-effectiveness evidence may help inform more context-sensitive treatment sequencing strategies beyond conventional line-of-therapy frameworks. Policy approaches such as price negotiation, optimized service delivery, and alternative dosing strategies may improve the value of esketamine for TRD management.
Tieosapjaroen W, Williams E, Johnson CC
… +14 more, Baptista Da Silva C, Barr-DiChiara M, Rodolph M, Ingold HL, Schmidt HA, Prochazka M, Msimanga B, Lastrucci C, Peralta H, Chitembo L, Andifasi P, Siegfried N, Landovitz RJ, Ong JJ
BACKGROUND: Long-acting injectable pre-exposure prophylaxis (LAI-PrEP) is a highly effective biomedical intervention for the prevention of HIV acquisition. There is a strong interest among communities and policymakers fo...BACKGROUND: Long-acting injectable pre-exposure prophylaxis (LAI-PrEP) is a highly effective biomedical intervention for the prevention of HIV acquisition. There is a strong interest among communities and policymakers for LAI-PrEP scale-up, accelerating the demand for clear guidance on testing approaches that balance accuracy with scalability. Unlike oral pre-exposure prophylaxis, LAI-PrEP may overcome adherence challenges, such as difficulty with frequent clinic visits. However, LAI-PrEP results in prolonged subtherapeutic drug levels after discontinuation, which can increase the risk of drug resistance among those who have an undetected HIV infection. This systematic review evaluates how different HIV testing strategies, including rapid diagnostic tests (RDTs), laboratory-based immunoassays and nucleic acid testing (NAT), affect clinical utility and programme delivery of LAI-PrEP. METHODS AND FINDINGS: We searched databases and retrieved studies up to April 8, 2025, and supplemented findings with data collected through a World Health Organization (WHO) survey among ongoing and completed LAI-PrEP implementation studies. We included publications reporting original or primary data on clinical, diagnostic and resource-use outcomes of HIV testing for LAI-PrEP. Meta-analyses were conducted using random-effects models. Chi-square tests were used to examine differences between related outcomes. Certainty of evidence was determined using the GRADE methodology (Prospero: CRD42024605562). Risk Of Bias In Non-randomised Studies of Interventions, Version 2 (ROBINS-I V2) assessment tool was used to assess bias for non-randomised comparative studies. Of 7,698 records identified, 38 reports representing 22 studies (cabotegravir: 20, lenacapavir: 2) across 15 countries were included. The overall certainty of evidence was low. Most were observational cohorts (n = 13) or non-randomised comparator studies (n = 7). Among 8,171 LAI-PrEP users in four randomised controlled trials, HIV detection rates were similar across strategies (9/8171 (RDT) versus 14/8171 (NAT) (Odds ratio (OR) 0.66 (95% confidence interval: 0.29-1.50; P = 0.87)), with no difference in adverse events. Compared with laboratory-based tests, RDTs enabled faster turnaround (same-day versus up to 7 days), more rapid treatment initiation (1 day versus 6-9 days), and lower test costs (US$4 versus US$22). All tests had similar negative predictive value (~100%) at LAI-PrEP initiation and comparable positive predictive value (~55%) at continuation. There was little difference in delayed HIV detection (11/8171 (RDT) versus 0/8171 (NAT)). In the HPTN 083 trial, NAT use was occasionally associated with false-positive results, leading to unnecessary PrEP holds or discontinuation (7/2483). NAT might have detected HIV before resistance emerged, though no prospective or modelling evidence showed clinical benefit at a population level. There was limited evidence of HIV self-testing for LAI-PrEP delivery. We noted that our assessment of performance accuracy in different testing strategies may introduce selection bias. CONCLUSIONS: RDT-based testing strategies have comparable accuracy to laboratory-based strategies and are more accessible and scalable, which can ensure that testing does not become a barrier to accessing or continuing LAI-PrEP. As countries expand access to LAI-PrEP amid increasingly constrained resources, adoption of new WHO guidance supporting the use of RDTs can enable simpler, more affordable, and user-centred HIV testing approaches.
BACKGROUND: Consumption of gabapentinoids has increased worldwide in recent years, and the association between its use and drug poisoning is of public health concern. This study aimed to investigate the association betwe...BACKGROUND: Consumption of gabapentinoids has increased worldwide in recent years, and the association between its use and drug poisoning is of public health concern. This study aimed to investigate the association between gabapentinoid treatment and the risk of drug poisoning. METHODS AND FINDINGS: In this within-individual study, we utilised data from the United Kingdom (UK) Clinical Practice Research Datalink (CPRD) Aurum database linked to the Hospital Episode Statistics (HES) and Office for National Statistics (ONS). The analysis included individuals aged 18 or above who were prescribed gabapentinoids and had an incident all-cause drug poisoning event between 1st January 2010 and 31st December 2020. Using the self-controlled case series (SCCS) design, we assessed the risk of drug poisoning incidence in predefined risk periods: 90 days before treatment initiation, first 28, 29-56, 57-84 days, and the remaining treatment time. Concomitant use with opioids/benzodiazepines was also evaluated. Adjusted incidence rate ratios (aIRRs) were calculated using conditional Poisson regression. A case-case-time-control (CCTC) analysis was also conducted, with adjusted odds ratio (aOR) calculated to validate the findings from the main SCCS analysis. All analyses have adjusted for key time-varying confounders, including age, season, and concomitant use of opioids, antiseizure medications, psychotropic medications, and non-steroidal anti-inflammatory drugs (NSAIDs). 16,827 individuals met the inclusion criteria and were included in the SCCS analysis. The risk of drug poisoning, compared with the reference periods, increased during the first 28 days of gabapentinoid treatment (aIRR = 1.81, 95% confidence interval [CI] [1.66, 1.99]; p < 0.001), eventually dropped to 1.11 (95% CI [1.05, 1.17]; p < 0.001) in the remainder of the treatment period. Notably, the risk was doubled during the 90-day preceding treatment initiation (aIRR = 2.09, 95% CI [1.98, 2.21]; p < 0.001). Co-administration with opioids elevated the risk by 30%, while benzodiazepines increased it 2-fold. The CCTC analysis also detected an increased aOR of 1.36 (95% CI [1.12, 1.65]; p = 0.002) of receiving gabapentinoid treatment within 30 days prior to a drug poisoning event. The SCCS approach cannot completely exclude the effect of unmeasured time-varying confounders, such as transient changes in socioeconomic status, major life events, or illicit drug use, although the negative control analysis did not suggest meaningful residual confounding. CONCLUSIONS: The results suggest that gabapentinoid is associated with an increased risk of drug poisoning. Close monitoring throughout gabapentinoid treatment journey for drug poisoning is needed, especially at the initial phase. Concomitant use with opioid or benzodiazepines should be avoided.
Circulating microbiome-related metabolites have emerged as promising biomarkers for coronary heart disease. A recent multi-stage study in PLOS Medicine strengthens signal prioritization but highlights the persistent gap...Circulating microbiome-related metabolites have emerged as promising biomarkers for coronary heart disease. A recent multi-stage study in PLOS Medicine strengthens signal prioritization but highlights the persistent gap between association and causality.
BACKGROUND: Although healthcare-associated transmission of Clostridioides difficile is a recognized public health concern, community-onset infections represent an important component of the overall disease burden. This p...BACKGROUND: Although healthcare-associated transmission of Clostridioides difficile is a recognized public health concern, community-onset infections represent an important component of the overall disease burden. This paradox likely reflects the underappreciated interplay between these settings. We aimed to quantify in-hospital transmission and the hospital's contribution to community colonization by estimating the intrinsic reproduction number (Ri) and introducing the colonization amplification index (Ai), defined as the ratio of colonized patients at discharge to those at admission. Given the potential contribution of external cases, we also evaluated interventions targeting asymptomatic carriers at admission to reduce disease burden. METHODS AND FINDINGS: We developed a compartmental model informed by data from UCSF Medical Center to capture C. difficile transmission dynamics among symptomatic and asymptomatic patients. Across simulations, the median Ri was 0.61 (Q1-Q3: 0.53, 0.71), consistently indicating limited sustained in-hospital transmission (Ri < 1). In contrast, Ai was 1.9 (Q1-Q3: 1.7, 2.1), suggesting substantial amplification of colonization during hospital stay. Amplification of colonization persisted in sensitivity analyses, with Ri exceeding 1 under boundary values of low colonization prevalence at admission, a low proportion of colonized patients progressing to symptomatic disease, and prolonged incubation periods. Redefining healthcare-associated C. difficile infection (CDI) using thresholds from ≥1-day post-admission instead of the standard threshold of >3 days post-admission increased Ai and Ri by 11% and 21%, respectively. A threshold of ≥5 days post-admission reduced these metrics by 5% and 8%, respectively. Interventions targeting asymptomatic carriers through contact precautions and/or prophylactic treatment reduced both Ai and CDI incidence, with combined interventions yielding the greatest reductions, followed by contact precautions alone. Our main limitation stems from uncertainty in some parameters describing the disease's natural history, particularly colonization prevalence at admission, progression to symptomatic disease, and the incubation period, which may affect the precision of our estimates despite sensitivity analyses. CONCLUSIONS: Our findings indicate that in most potential scenarios, in-hospital transmission of C. difficile is limited (Ri < 1) and likely sustained by continuous importation of cases from the community. Nevertheless, hospitalization amplifies colonization (Ai > 1), which potentially contributes to community transmission. These results underscore the importance of interventions addressing asymptomatic carriers, a currently overlooked source of spread. Our study highlights the need to broaden metrics beyond Ri to capture hospitals' contribution to the C. difficile burden. Future infection control strategies should address colonization dynamics at admission and potentially at discharge to mitigate transmission and reduce the overall burden of C. difficile.
BACKGROUND: Clinical guidance in Canada and the United States recommends faster methadone dose titration for individuals using fentanyl. An initial dose increase is recommended between days 4 and 6, but the impact on pat...BACKGROUND: Clinical guidance in Canada and the United States recommends faster methadone dose titration for individuals using fentanyl. An initial dose increase is recommended between days 4 and 6, but the impact on patient outcomes remains unclear, particularly when provided in an outpatient setting. Therefore, we evaluated the association between early methadone dose titration (i.e., within treatment days 4-6) and treatment discontinuation and opioid toxicity. METHODS AND FINDINGS: We conducted a retrospective propensity-score weighted cohort study of Ontario residents who initiated methadone in an outpatient setting between January 2017 and December 2022. Exposure was defined as provision of a dose titration between treatment days 4-6, with the index date defined as the first date of dose increase. For unexposed individuals, the index date was randomly assigned and followed the same distribution as those exposed. Individuals were followed for up to 181 days following index date for study outcomes. Primary outcomes included methadone discontinuation and opioid toxicity, using an intention-to-treat approach. Secondary outcomes included methadone versus non-methadone-related toxicity while on treatment. We fit a propensity-score model to estimate the probability of dose titration, conditional on baseline demographic and clinical (e.g., comorbidities, past medication use) variables. Propensity score weighted Cox proportional hazard models were then estimated to determine the association between early dose titration and study outcomes. Among 13,560 incident methadone recipients (61.4% [N = 8,322] provided early dose titration), the mean age was 36.5 years old, and approximately one-third were female. Individuals who received an early dose titration had a lower weighted hazard of discontinuation, which was most pronounced during the first seven days of follow-up (weighted hazard ratio [wHR]: 0.55; 95% confidence interval [CI]: 0.51, 0.60), with attenuation towards the null over time. The observed weighted rate of opioid toxicity was lower among those exposed versus unexposed (10.1 versus 12.3 per 100 person-years; wHR: 0.82; [95% CI: 0.69, 0.97]). Early dose titration was not associated with opioid toxicity while on treatment. Most toxicities were attributed to non-methadone opioids (exposed: 3.89 per 100 person-years versus unexposed: 4.06 per 100 person-years; wHR: 1.00; [95% CI: 0.70, 1.44]). Methadone-related toxicity while on treatment remained low and comparable between exposed and unexposed groups (2.02 versus 2.65 per 100 person-years; wHR: 0.80; [95% CI: 0.46, 1.41]). The main study limitation is the lack of information on drug use history and time-varying clinical factors that may influence both dose titration and subsequent outcomes, introducing the potential for residual confounding. CONCLUSIONS: This population-based analysis demonstrated that early methadone dose titration was associated with improved treatment retention and lower hazard of opioid toxicity. Logistical barriers that hinder timely provision of dose increases must be addressed to improve methadone retention among people who use fentanyl.
Integrating spatial omics with artificial intelligence is likely to advance biomarker research and diagnostics, with the potential to pair mechanistic insight into spatial target biology. By developing scalable, reproduc...Integrating spatial omics with artificial intelligence is likely to advance biomarker research and diagnostics, with the potential to pair mechanistic insight into spatial target biology. By developing scalable, reproducible quantification in routine pathology, it can help bridge discovery, validation, and real-world clinical implementation.
BACKGROUND: Early-life exposure to per- and polyfluoroalkyl substances (PFAS) may impact the developing lungs and immune system and increase the risk of childhood asthma, but no studies have been conducted in a high-expo...BACKGROUND: Early-life exposure to per- and polyfluoroalkyl substances (PFAS) may impact the developing lungs and immune system and increase the risk of childhood asthma, but no studies have been conducted in a high-exposed population. The objective of this study was to estimate associations between prenatal PFAS exposure and childhood incidence of asthma and wheeze in Blekinge County, Sweden, where a subset of residents in the city of Ronneby was exposed to PFAS from drinking water contaminated by aqueous film-forming foam (AFFF). METHODS AND FINDINGS: We constructed a register-based open cohort of 11,488 children born in Blekinge county between 2006 and 2013 and followed each individual from birth until age 12 or December 31, 2022. Maternal address history was linked to water distribution records to create a categorical proxy variable for prenatal PFAS exposure from drinking water. We identified incident cases of wheeze and asthma from administrative health records and estimated hazard ratios (HRs) using Cox proportional hazards models adjusted for individual-level confounders, including maternal smoking in early pregnancy, maternal age at delivery, parity, child sex, parental asthma, and socioeconomic factors. As a secondary analysis, we applied a Rubin Causal Model (RCM) analysis to estimate the average marginal effect of prenatal PFAS exposure on wheeze and asthma among the very highly-exposed population, using a matched dataset of very-high and background-exposed individuals balanced on measured confounders. Overall, 18% of children were diagnosed with wheeze and 17% with asthma during follow-up. Very high prenatal PFAS exposure was associated with incidence of asthma (HR: 1.44, 95% CI [1.08, 1.92]), whereas no associations were observed for the high or intermediate exposure groups or for wheeze. In the RCM analysis, the estimated cumulative incidence of asthma was 16.1% in the background-exposed group and 26.7% in the very highly exposed group (Fisherian p < 0.001). Study limitations include reliance on an address-based categorical proxy for prenatal PFAS exposure, which likely results in non-differential exposure misclassification and limits the ability to distinguish prenatal from early-childhood exposure effects. CONCLUSIONS: In this study, very high prenatal PFAS exposure was associated with a higher incidence of childhood asthma. Although these results should be replicated, they suggest an important public health impact of AFFF-associated PFAS contamination.
BACKGROUND: Global investments to combat HIV, tuberculosis, and malaria (HTM) have delivered substantial health gains and may have reduced the burden placed by these diseases on the routine health system. We estimated th...BACKGROUND: Global investments to combat HIV, tuberculosis, and malaria (HTM) have delivered substantial health gains and may have reduced the burden placed by these diseases on the routine health system. We estimated the reduction in primary healthcare (PHC) utilization resulting from the scale-up of HTM services over 2000-2023 in 108 low- and middle-income countries. METHODS AND FINDINGS: For each disease, we applied established mathematical models to quantify PHC utilization (outpatient visits and inpatient bed-days provided outside of HTM programs) by individuals with symptomatic HIV, tuberculosis, or malaria unable to access HTM-specific services. For each country, we estimated averted PHC utilization by comparing a scenario describing the actual scale-up of HTM services to a counterfactual scenario holding HTM service coverage constant at year 2000 levels. We applied published unit costs to estimate the averted costs resulting from reduced PHC utilization. Over 2000-2023, scale-up of HTM services averted an estimated 6.9 (95% uncertainty interval (UI) [4.4, 10.5]) billion outpatient PHC visits and 3.9 (95% UI [2.5, 5.9]) billion inpatient bed-days, representing US$135 (95% UI [71, 250]) billion in averted costs. These reductions were greatest in sub-Saharan Africa and East Asia and Pacific regions. Across study countries, these reductions represented a median of 4.4% of hospital bed capacity and 1.6% of government health spending in 2023. These percentages were 22.9% and 5.1%, respectively, for low-income countries. Our analysis did not consider changes in PHC services beyond utilization. Also, several inputs were missing in some countries, with missing values estimated using regression imputation. CONCLUSIONS: Over recent decades, sustained investments in HTM services in high-burden settings have averted substantial PHC utilization and associated costs. These benefits should be considered when assessing investment impact.
BACKGROUND: Dementia, cardiovascular disease (CVD), and functional impairment (FI) often co-occur in aging populations, with abdominal obesity as a shared modifiable risk factor. The long-term impact of abdominal obesity...BACKGROUND: Dementia, cardiovascular disease (CVD), and functional impairment (FI) often co-occur in aging populations, with abdominal obesity as a shared modifiable risk factor. The long-term impact of abdominal obesity on these comorbidities is unclear. We projected the 30-year burden of dementia, FI, and CVD in China under different trajectories of abdominal obesity prevalence. METHODS AND FINDINGS: We modeled three trajectories of abdominal obesity prevalence from 2020 to 2050 using data from the China Health and Nutrition Survey (2000-2015): continuation of the observed growth prevalence trend (persistent), stabilization at 2015 levels (optimal), and a 50% reduction in the growth rate (improved). Abdominal obesity was defined as a waist circumference of ≥90 cm for men and ≥85 cm for women. A Markov model was used to estimate occurrence of dementia, CVD, FI, and mortality among adults aged ≥65 years by sex and year. Under the persistent scenario, dementia cases were projected to rise to 37.8 million (95% uncertainty interval (UI) [36.7, 38.9]) by 2050, alongside 68.1 million (95% UI [66.7, 69.5]) cases of FI, 198.3 million (95% UI [196.5, 200.4]) CVD cases, and 17.6 million (95% UI [16.5, 18.7]) deaths. Compared with the persistent scenario, dementia and FI burdens increased under the optimal and improved scenarios by 2050, by 1396.0 thousand (95% UI [589.1, 2293.9]) and 711.4 thousand (95% UI [294.4, 1150.3]) for dementia, and by 2570.6 thousand (95% UI [1081.0, 4024.9]) and 1289.5 thousand (95% UI [569.5, 2034.2]) for FI, mainly due to reduced CVD mortality expanding the population at risk. These shifts are most pronounced among adults aged ≥80 years and women. For CVD, reductions in the number of cases were projected in the short term (by 2030), but these changes remain uncertain by 2050. Main limitations include the assumption that other risk factors remain unchanged, and the lack of modeling of multiple co-occurring dementia's risk factors. CONCLUSIONS: Abdominal obesity control may reduce CVD incidence and mortality, thereby shifting the disease burden toward dementia and FI due to increased longevity, highlighting the need for integrated, life-course public health strategies responsive to the patterns of dementia and its comorbidity in older people.
BACKGROUND: Urban and rural settings differ in key determinants of tuberculosis (TB) burden, including transmission dynamics, social and structural determinants, and healthcare access. However, understanding of urban and...BACKGROUND: Urban and rural settings differ in key determinants of tuberculosis (TB) burden, including transmission dynamics, social and structural determinants, and healthcare access. However, understanding of urban and rural TB burden is limited, hindering implementation of public health interventions to end TB. METHODS AND FINDINGS: We conducted a systematic review and meta-analysis of urban and rural differences in adult pulmonary TB prevalence in low- and middle-income countries. We searched PubMed, Embase, Global Health, the Cochrane Library, Africa Index Medicus, LILACS, and SciELO for community-representative prevalence surveys conducted between 1st January 1993 and 14th October 2025. Studies focussing solely on symptomatic or healthcare-seeking individuals and those conducted in congregate settings like prisons, universities, and health facilities were excluded. Risk of bias was assessed using a tool for prevalence surveys. Bayesian multilevel meta-regression was used to estimate pooled urban-to-rural prevalence ratios (PR) for bacteriologically-confirmed and smear-positive TB overall, and by World Health Organization (WHO) region. We also investigated time trends in the urban-to-rural prevalence ratio, and associations between urban-to-rural prevalence ratios and survey-level risk of bias (not low versus low), TB screening algorithm (whether used symptom screening for sputum eligibility), national TB incidence, percentage of population living in urban areas, and representativeness of prevalence surveys (national versus sub-national). To estimate the number of people with prevalent TB in urban and rural areas in study countries, and how these have changed between 2000 and 2024, we fitted a Bayesian multivariate model to WHO incidence and case detection ratio data and combined these estimates with assumptions about the duration of treated and untreated TB and the distribution of urban and rural populations. We included 47 surveys conducted between 2000 and 2024, encompassing 2,454,443 participants. The pooled urban-to-rural PR of bacteriologically-confirmed TB was 1.09 (95% credible interval [CrI]: 0.90, 1.30) and was 1.24 (95% CrI: 0.94, 1.61) for smear-positive TB. However, there were substantial differences between WHO regions: averaged across the 24 year study period the African Region had higher urban bacteriologically-confirmed prevalence (PR 1.18, 95% CrI: 0.91, 1.52), while the Western Pacific Region (PR 0.85, 95% CrI: 0.64, 1.07) and South-East Asia Region (PR 0.86, 95% CrI: 0.67, 1.08) had broadly similar urban and rural prevalence. Time trends indicated an increase in the overall bacteriologically-confirmed urban-to-rural prevalence ratio between 2000 and 2024, with a mean PR increase of 2.4% (95% CrI: -0.8%, 6.0%) per year. We estimated that, for 2024 in the 26 represented study countries (combined population: 2.24 billion [48.3%] urban; 2.40 billion [51.7%] rural), 49% (6.6 million, 95% CrI: 4.2, 12.0 million) of prevalent TB was in urban areas, and 51% (6.8 million, 95% CrI: 4.2, 12.0 million) in rural areas. Within countries, there were striking changes in the urban and rural distribution between 2000 and 2024, with the share of urban cases increasing in nearly all countries. The main limitations include lack of unified definitions for urban and rural areas, and absence of data for some global regions (e.g., Americas and Europe). CONCLUSION: Between 2000 and 2024, TB epidemics have become increasingly urbanised, both in proportional and absolute terms, although with considerable variation in timing across countries and regions. Public health approaches tailored to urban and rural TB epidemiology and demography will be required to end TB.
BACKGROUND: Current tuberculosis (TB) prevention and care strategies have failed to reduce disease burden at the pace required to meet global targets. Community screening may enable more rapid declines in TB burden, but...BACKGROUND: Current tuberculosis (TB) prevention and care strategies have failed to reduce disease burden at the pace required to meet global targets. Community screening may enable more rapid declines in TB burden, but evidence is limited. We used mathematical modelling to evaluate approaches using different diagnostic algorithms, population coverage, and duration of screening. METHODS AND FINDINGS: We used a deterministic compartmental TB model, which recognised symptomatic and asymptomatic infectious TB (defined by whether an individual reported symptoms at screening), as well as noninfectious TB. We simulated diagnostic algorithms targeting symptomatic infectious TB (prolonged cough with confirmatory Xpert Ultra), infectious TB (Xpert Ultra), or all TB (chest X-ray), and we varied population coverage and duration of screening. Main outcomes were estimated reduction in symptomatic TB incidence and TB mortality over a 10-year horizon. Maximum coverage (100%) and duration (five annual rounds) was projected to reduce symptomatic TB incidence by 26.9% (UI 22.8, 31.5%) with the algorithm targeting symptomatic TB and 74.0% (UI 68.5, 79.1%) with the algorithm targeting infectious TB. However, incidence rebounded at the end of screening, erasing 9.8% and 15.9%, respectively, of those reductions within 5 years. The algorithm targeting all TB showed higher potential for rapid reductions-over 98%-with negligible rebound; however, low diagnostic accuracy of current tools led to prohibitive overdiagnosis, with 7.2 false positives per true positive in a single round of screening. Screening algorithms targeting broader disease definitions (infectious or all TB) generally achieved greater impact with lower population coverage and/or duration. Findings were broadly similar for mortality. As a modelling study, our approach assumed a homogeneous population for simplicity and required assumptions where data were lacking around algorithm performance, treatment acceptance, and treatment completion across disease states. CONCLUSIONS: We show that substantial reductions in TB morbidity and mortality can be achieved by community screening, highlighting the importance of symptom-agnostic algorithms and the need to balance population coverage and duration. To maximise and sustain epidemiological impact, accurate diagnostic tools and appropriate treatment regimens for individuals with noninfectious TB are needed.
BACKGROUND: While physical frailty is linked to psychiatric disorders, its association with suicide attempt (SA) risk is unclear. We aimed to investigate the prospective association of physical frailty with SA risk and t...BACKGROUND: While physical frailty is linked to psychiatric disorders, its association with suicide attempt (SA) risk is unclear. We aimed to investigate the prospective association of physical frailty with SA risk and the modifying and potential mediating roles of genetic risk and blood biomarkers. METHODS AND FINDINGS: This cohort study included 442,920 UK Biobank participants free of SA at baseline. SA events were extracted by linking hospital inpatient records. Physical frailty status was assessed using the five-component Fried phenotype and categorized as nonfrail, prefrail, or frail. Genetic risk for SA was estimated through polygenic risk scores and categorized into high, intermediate, and low risk levels. Cox proportional hazard models were conducted to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association. Mendelian randomization (MR) analyses were utilized to examine the association between genetically determined physical frailty and SA. Mediation analyses were performed to explore potential biological pathways involving circulating biomarkers. During a median follow-up of 13.6 years, 1,518 (0.3%) individuals developed SA. After multivariable adjustment for sociodemographic characteristics, genetic risk, lifestyle factors, psychiatric disorders, cardiovascular diseases, and cancer, the HRs for SA among those with pre-frailty were 1.61 (95% CI [1.44, 1.80]; P < 0.001) and frailty were 2.16 (95% CI [1.78, 2.61]; P < 0.001) compared with nonfrail individuals. Genetically predicted frailty was also positively associated with SA (odds ratio = 2.06, 95% CI [1.21, 3.52]; P = 0.008). Except for low physical activity, all frailty components were significantly associated with an increased risk of SA (all P < 0.05), with HRs ranging from 1.16 (95% CI [1.01, 1.33]; P = 0.038) to 1.62 (95% CI [1.43, 1.82]; P < 0.001). The additive interaction of physical frailty and genetic risk increased the risk of SA, with the highest risk observed among frail individuals with high genetic risk (HR = 3.09, 95% CI [2.30, 4.17]; P < 0.001), whereas no significant multiplicative interactions were detected. Biomarkers related to liver function, metabolism, immunity, and inflammation may have partially explained this association, accounting for a collective 14.15% (95% CI: 8.94%, 19.74%; P < 0.001) of the total effect, although MR analyses did not support causal mediating effects. The key limitations of this analysis include potential residual confounders and the limited representativeness of the study population. CONCLUSIONS: Pre-frail and frail states were associated with an increased risk of SA, especially among individuals with high genetic risk. Incorporating frailty assessment and management into primary prevention strategies may have implications for SA prevention.
BACKGROUND: Promoting handwashing with soap reduces risk of diarrhoea by 30% and respiratory infections by 17%. Handwashing promotion in nonhealthcare settings is widely considered cost-effective, but there is no systema...BACKGROUND: Promoting handwashing with soap reduces risk of diarrhoea by 30% and respiratory infections by 17%. Handwashing promotion in nonhealthcare settings is widely considered cost-effective, but there is no systematic review on this topic. To inform resource allocation decisions, we reviewed the state and quality of evidence regarding cost-effectiveness and benefit-cost of interventions promoting handwashing with soap in domestic, educational, and childcare settings globally. METHODS AND FINDINGS: We searched Medline, Embase, Global Health, EconLit, and Web of Science for studies published from January 1, 1980 to September 3, 2025, as well as grey literature (PROSPERO CRD42021288727). We included full economic evaluations comparing the cost of two or more interventions with their outcomes. We included interventions promoting the practice of handwashing with soap, including those providing information, motivational campaigns, and/or handwashing facilities. We scored quality of reporting using the Consolidated Health Economic Evaluation Reporting Standards. We identified 15 studies of which 3 were in high-income countries. Five used empirical data collection to evaluate interventions actually implemented and 10 modelled from secondary data only. Amongst the 3 medium- or high-quality studies reporting cost per disability-adjusted life-year averted, estimates ranged from US$ 37 to 937 (2024 prices). Of these 3 estimates, 2 were cost-effective compared to plausible thresholds for the respective country. In the only medium- or high-quality benefit-cost study, the mean benefit-cost ratio was 2.1 with "medium" levels of handwashing adoption (40% of population) and adherence (50% of those adopting). Few studies measured or modelled adoption of handwashing over time, and none which focussed on diarrhoea also valued respiratory infections. Limitations of our review include that we excluded alcohol-based handrub interventions, and that there is high uncertainty about cost-effectiveness thresholds. CONCLUSIONS: Promoting handwashing with soap is very likely to be cost-effective for interventions that successfully increase and sustain adoption of handwashing behaviours. More empirical studies are needed, especially those comparing multiple promotion options and valuing reductions in respiratory infections as well as diarrhoea.
A recent lawsuit against "hyper-palatable" ultra-processed foods has amplified controversies over its effects on obesity-related chronic disease. Addressing this public health crisis requires a new framework, centered on...A recent lawsuit against "hyper-palatable" ultra-processed foods has amplified controversies over its effects on obesity-related chronic disease. Addressing this public health crisis requires a new framework, centered on the metabolic effects of food.
BACKGROUND: Sugary drink taxes have been implemented in several U.S. jurisdictions, but we know little about the impact of taxes on calories purchased in restaurants. The impact may differ in restaurant (vs. non-restaura...BACKGROUND: Sugary drink taxes have been implemented in several U.S. jurisdictions, but we know little about the impact of taxes on calories purchased in restaurants. The impact may differ in restaurant (vs. non-restaurant) settings because restaurant consumers may be less likely to travel to other jurisdictions for a single meal, choose no beverage or non-taxed beverages, decrease their beverage size, or order combo meals where the drink is bundled with other items at a single price. METHODS AND FINDINGS: We used six years of transaction-level sales data (2015-2020) from 7,341 Taco Bell restaurant locations to estimate the association of sugary drink policies with beverage calories purchased in the drive-through setting of fast food restaurants over time. Taco Bell restaurants represents a large sample size of data from several U.S. jurisdictions across a long follow-up period, which is unique in the literature. We defined the treatment group as restaurants in five jurisdictions where taxes were ever implemented (Albany, CA; Cook County, IL; Oakland, CA; Philadelphia, PA; Seattle, WA) (n = 60 restaurants). We identified a group of comparison restaurants where taxes were never implemented using synthetic control methods (n = 60 restaurants). We used a difference-in-differences design with calendar month and restaurant fixed effects to compare changes in outcomes between groups between the baseline (3-14 months prior to tax implementation) and 3- to 24-month follow-up periods, overall and by jurisdiction. Our primary outcome measure was beverage calories per transaction, from individually-purchased beverages and combo meals (separately). In the baseline period, average beverage calories per transaction were 51.1 (SD = 8.6) in the tax group and 42.3 (SD = 7.4) in the comparison group; and 119.5 (SD = 15.3) and 115.0 (SD = 23.0) beverage calories per transaction in combo meals. Overall, we observed no association between taxes and changes in beverage calories per transaction between groups during the follow-up period, including from individual beverage items (difference-in-differences = -0.3 (95% CI [-0.8, 1.2]) and combo meals (difference-in-differences = -4.3 (95% CI [-13.5, 5.0]). We observed similar results by location, except in Oakland, CA, where customers purchased 16.8 (95% CI 19.6, 14.1) fewer beverage calories per transaction from combo meals; the association was null after conditioning on the purchase of a beverage (difference-in-differences = -1.01 [-4.93, 2.92)]). The main limitations of our study methodology include the exclusion of beverage calorie data from in-store transactions and that the majority of the restaurants in our sample were located in Cook County. CONCLUSIONS: Though we observed differences in certain jurisdictions, overall our findings suggest that sugary drink taxes may not be effective in reducing beverage calorie consumption in fast food restaurants.
Oral systemic anti-cancer therapies improve convenience, but also shift responsibility for treatment management to the patient. Education, communication, and models of care must adapt to support safe, equitable, and sust...Oral systemic anti-cancer therapies improve convenience, but also shift responsibility for treatment management to the patient. Education, communication, and models of care must adapt to support safe, equitable, and sustainable oral anti-cancer treatment.
BACKGROUND: Resource Constrained Situations (RCS) at Emergency Medical Dispatch centers where there are more patients requiring an ambulance than there are available ambulances are common. Machine Learning (ML) technique...BACKGROUND: Resource Constrained Situations (RCS) at Emergency Medical Dispatch centers where there are more patients requiring an ambulance than there are available ambulances are common. Machine Learning (ML) techniques offer a promising but largely untested approach to assessing relative risks among these patients. The study aims to establish whether the provision of ML-based risk scores predicting patient outcomes improves the ability of dispatchers to identify patients at high risk for deterioration in RCS and dispatch the first available ambulance to them. METHODS AND FINDINGS: We performed a parallel-group, randomized trial of adult patients assessed by a dispatch nurse at two study sites in Sweden as requiring a low-priority ambulance response in RCS. Patients were randomized 1:1 to be prioritized with the aid of an ML-based risk assessment tool, or per current clinical practice. The primary outcome was defined in terms of whether the first available ambulance was sent to the patient with the highest National Early Warning Score (NEWS 2) based on subsequently collected vital signs. A total of 1,245 RCS were included in the study. In the intervention arm, 68.3% of RCS were assessed correctly per the primary outcome versus 62.5% in the control group, corresponding to an odds ratio of 1.28 (95% CI [1.00, 1.63], p = 0.047). This study was limited to only patients determined to require a low-priority ambulance response in two Swedish regions, and was underpowered for the primary outcome due to a smaller than expected sample size. CONCLUSION: This study suggests that clinical ML-based decision support tools may have the ability to influence care provider decisions and improve their capacity to rapidly differentiate between high- and low-risk patients at dispatch. Further research should establish the suitability of these tools in larger cohorts, for patients with both higher- and lower-levels of priority, and in other settings. The trial was registered at ClinicalTrials.gov (NCT04757194).