PLoS Med. [JOURNAL]
Sun
200 papers
Impact of supermarket fruit and vegetable placement on store sales, customer purchasing, diet and household waste: A prospective matched-controlled cluster trial.
Vogel C, Crozier S, Dhuria P … +7 more , Lord J, Moon G, Lawrence W, Cade J, Ball K, Cooper C, Baird J
PLoS Med · 2026 Mar · PMID 41915648 · Full text
BACKGROUND: Previous product placement trials have been underpowered and limited in outcomes. This study assessed effects of positioning an expanded fruit and vegetable section near entrances on store-level sales, househ...
BACKGROUND: Previous product placement trials have been underpowered and limited in outcomes. This study assessed effects of positioning an expanded fruit and vegetable section near entrances on store-level sales, household-level purchasing and waste, and dietary behaviours. METHODS AND FINDINGS: This prospective matched controlled cluster trial (NIHR 17/44/46) involved 36 stores (18 intervention and 18 control) of a discount supermarket chain in England. The study took place between March 2018 and May 2022, and the intervention was implemented for six months. Control stores were matched on store sales, customer profiles and neighbourhood deprivation. Women customers aged 18-60 years, with loyalty cards, who shopped at intervention (n = 280) or control (n = 300) stores agreed to participate. The primary outcome was household purchasing of fresh fruit and vegetables. Secondary outcomes included: i) differences in household purchasing by educational attainment, ii) store sales of fresh fruit and vegetables, iii) dietary quality score for woman, and iv) child aged 2-6 years (if relevant), and v) household fruit and vegetable waste. The proportion of households purchasing fruit and vegetables in intervention compared to control stores was very similar at baseline (-0.1% (95%CI -6.1%, 6.0%)). After 3 months of exposure to the intervention, the proportion was 0.6% (95%CI -5.6%, 6.7%; p = 0.83) and after 6 months the proportion was 3.3% (95%CI -2.5%, 9.2%; p = 0.23). Interrupted time series analyses showed differences in intervention compared to predicted store-level sales of fruit and vegetables were 0.32SDs (95%CI 0.11, 0.53; p = 0.002) at intervention implementation, equivalent to ~2,525 (95% CI 775, 4,115) extra portions per store, per week. The differences were 0.23SDs (95%CI -0.05, 0.52; p = 0.10) at 3 months and 0.18SDs (-0.16, 0.52); p = 0.29) at 6 months post-intervention. Not being able to randomise stores potentially biases the results through unmeasured confounding effects and findings related to intervention dose were not prespecified but determined from process evaluation findings investigating intervention implementation. CONCLUSIONS: This study was conducted during the COVID-19 pandemic and cost-of-living crisis when population level fruit and vegetable sales and intake declined and recruitment to research was challenging. Despite these circumstances, the results of this study show that positioning produce sections near supermarket entrances may improve the nutrition profile of store sales, household purchasing and women's dietary quality. TRIAL REGISTRATION: NCT03573973.
Effect of enhanced peer PrEP referral with HIV self-testing delivery among young Kenyan women: A randomized controlled trial of peer networks.
Ortblad KF, Wairimu N, Culquichicon C … +12 more , Njeru I, Malen RC, Reedy AM, Ekwunife O, McGowan M, Mwangi M, Muthoni A, Kiboi D, Njoroge S, Gao F, Baeten JM, Ngure K
PLoS Med · 2026 Mar · PMID 41911315 · Full text
BACKGROUND: Adolescent girls and young women (AGYW) in Africa experience high HIV acquisition risk and low engagement in prevention services. Knowledge of HIV-negative status paired with peer support might motivate AGYW-...
BACKGROUND: Adolescent girls and young women (AGYW) in Africa experience high HIV acquisition risk and low engagement in prevention services. Knowledge of HIV-negative status paired with peer support might motivate AGYW-who are highly socially connected-to initiate HIV prevention services, including pre-exposure prophylaxis (PrEP). METHODS AND FINDINGS: We conducted a randomized controlled trial (ClinicalTrials.gov: NCT04982250) of AGYW peer networks in Central Kenya. Index peers aged 16-24 years who had used oral PrEP in the past 12 months were randomized 1:1 to: (1) enhanced peer referral: group training on PrEP referral strategies and delivery of HIV self-testing (HIVST) kits (n = 8 kits, 2 kits/peer); or (2) standard peer referral: informal PrEP referral strategies. Index peers were encouraged to refer four peers who could benefit from PrEP. Outcomes for referred peers-PrEP initiation (primary), PrEP continuation (i.e., month one refills), and HIV testing (any form following referral)-were reported by index peers three months later. Implementation outcomes and costs were also assessed. Risk differences (RDs) were estimated using generalized linear mixed-effects regression models with study group fixed effects and index peer random effects. From May 3, 2023 to February 16, 2024, 316 index peers were screened and 82 enrolled/randomized (median age 22 years, IQR 20-23): 40 to the enhanced group and 42 to the standard. No index peers were lost to follow-up. Index peers reported outcomes for 241 referred peers (median age 22 years, IQR 21-24): 137 in the enhanced group and 104 in the standard. At follow-up, there were no significant differences in PrEP initiation between the enhanced group (30%, 41/137) and the standard (41%, 41/104; RD -6%, 95% CI [-26%, 11%], p = 0.51). Enhanced peer referral was not associated with PrEP continuation (RD 1%, 95% CI [-10%, 13%], p = 0.82) but was associated with increased recent HIV testing (RD 39%, 95% CI [24%, 54%], p < 0.001). Three referred peers, all in the enhanced group, tested HIV-positive; two social harms (verbal abuse among index peers, one in each group) were reported. Index and referred peers in both study groups found enhanced peer referral acceptable and feasible, but it cost almost eight times more per peer referred to PrEP than standard referral ($23 versus $3 USD). Relying on index peers to report outcomes for referred peers was a study limitation. CONCLUSIONS: Enhanced peer PrEP referral with training and HIVST delivery did not increase PrEP initiation among Kenyan AGYW but was associated with increased HIV testing, suggesting opportunities to combine peer-delivered HIVST with additional implementation strategies to improve AGYW's PrEP engagement.
The future of medicine in a One Health world.
Gittleman JL
PLoS Med · 2026 Mar · PMID 41894643 · Full text
Long recognized as a breakthrough approach, One Health has been slow and piecemeal to infiltrate medical fields. Growing evidence suggests that it's time for change by taking on a new patient-the environment.
Long recognized as a breakthrough approach, One Health has been slow and piecemeal to infiltrate medical fields. Growing evidence suggests that it's time for change by taking on a new patient-the environment.
A responsible authorship culture is needed and it is a collective responsibility.
Kiermer V, Bibbins-Domingo K, Skipper M
PLoS Med · 2026 Mar · PMID 41886509 · Full text
In this Formal Comment, representatives from PLOS, Nature and JAMA call for action on adopting a principle-based approach for a responsible authorship culture.
In this Formal Comment, representatives from PLOS, Nature and JAMA call for action on adopting a principle-based approach for a responsible authorship culture.
Policy stringency during the COVID-19 pandemic and healthcare services utilization in China: An interrupted time-series analysis.
Xiao H, Bai G, Liu F … +2 more , Cui Y, Unger JM
PLoS Med · 2026 Mar · PMID 41886488 · Full text
BACKGROUND: The COVID-19 pandemic has profoundly impacted healthcare systems worldwide, with China presenting a unique case. As the first country to report COVID-19 cases and the last to lift its stringent Zero-COVID pol...
BACKGROUND: The COVID-19 pandemic has profoundly impacted healthcare systems worldwide, with China presenting a unique case. As the first country to report COVID-19 cases and the last to lift its stringent Zero-COVID policy, China presents a distinctive context for understanding the long-term effects of the pandemic on healthcare utilization. This study provides a comprehensive analysis of healthcare utilization trends in China over more than four years of the pandemic, focusing on how different phases, including the Zero-COVID policy and its cessation. METHODS AND FINDINGS: We conducted an interrupted time-series analysis of monthly healthcare utilization data from January 2015 to April 2024, including outpatient visits and inpatient discharges, across Mainland China, controlling for underlying secular trends and patterns. Hospital-based healthcare utilization data were sourced from the National Health Commission of China, and daily Policy Stringency Indices (higher values indicating stricter control policies) were obtained from Oxford's COVID-19 Government Response Tracker. We modeled changes in healthcare utilization using negative binomial regression, comparing actual outcomes with counterfactual estimates based on pre-COVID trends. We assessed healthcare utilization during key pandemic phases, including the post-Zero-COVID period. Healthcare utilization in China experienced substantial declines during the pandemic, with an estimated reduction of 1.21 billion (7%) outpatient visits and 140.9 million (13%) inpatient discharges compared to expected levels from January 2020 to April 2024. The most pronounced declines occurred during the initial pandemic waves and coincided with periods of stringent Zero-COVID measures. Negative associations between the Policy Stringency Index and healthcare utilizations were observed. Before the lifting of the Zero-COVID policy, a 10-point increase in the Policy Stringency Index was associated with a 7.2 percentage point decrease in outpatient visits and a 6.2 percentage point decrease in hospitalizations. Although healthcare utilization gradually rebounded following the cessation of the Zero-COVID policy, as of April 2024, utilization remained below expected levels in 20 (65%) of the 31 regions for outpatient visits and in 23 (74%) for inpatient discharges. Regional disparities were evident, with more developed areas, such as Shanghai and Beijing, experiencing the largest absolute reductions after adjusting for population size. In Shanghai, outpatient visits declined by 4,997 and hospitalizations by 241 per 1,000 people. In contrast, the largest relative reductions occurred in less developed regions, where outpatient visits dropped by 16% in Guizhou and hospitalizations declined by 27% in Shanxi. Use of aggregated routine health system data limited individual-level analyses, assessment of care quality, and disentangling of causal pathways. CONCLUSIONS: The COVID-19 pandemic and Zero-COVID policies were associated with substantial and enduring disruptions to healthcare utilization in China, characterized by slow recovery and regional disparities in access. These findings underscore the importance of strengthening healthcare systems to enhance resilience and better balance public health interventions with the maintenance of essential healthcare services in anticipation of future public health crises. Continued targeted efforts are needed to address the delayed recovery, particularly in regions with already strained healthcare infrastructure, and to ensure equitable healthcare access across the country.
Pain and treatment outcomes after initiating methadone vs buprenorphine among medicare patients with opioid use disorder and comorbid chronic pain: A target trial emulation.
Wei YJ, Winterstein AG, Fillingim RB … +2 more , Schmidt S, Schmidt S
PLoS Med · 2026 Mar · PMID 41886442 · Full text
BACKGROUND: Methadone and buprenorphine, effective treatments for opioid use disorder (OUD), also provide analgesia for managing pain, which is commonly experienced by patients with OUD. Limited population-based evidence...
BACKGROUND: Methadone and buprenorphine, effective treatments for opioid use disorder (OUD), also provide analgesia for managing pain, which is commonly experienced by patients with OUD. Limited population-based evidence exists comparing pain-related and treatment outcomes for methadone versus buprenorphine among patients with OUD and comorbid pain. The study aims to examine pain-related and treatment outcomes among Medicare patients with comorbid pain and OUD who initiated methadone or buprenorphine. METHODS AND FINDINGS: We conducted a retrospective cohort study with target trial emulation using the 100% Medicare data from 2020 to 2023. Participants included patients with comorbid chronic pain and OUD who initiated methadone or buprenorphine. The key dependent variables were pain-related outcomes that included hospitalization and emergency department (ED) visit due to pain, and treatment outcomes that included opioid overdose and all-cause mortality. Outcomes were assessed 1 year following treatment initiation. Intention-to-treat and per-protocol analyses were conducted to estimate incidence rate ratios (IRRs) for pain-related outcomes and opioid overdose and hazard ratios (HRs) for all-cause mortality. For each outcome, we also calculated the adjusted risk difference (aRD) between the methadone and buprenorphine groups. We identified 49,727 eligible Medicare patients (mean [SD] age, 59.0 [11.6] years; 24,538 [49.3%] female and 25,189 [50.7%] male). Of the identified patients, 16,174 (32.5%) initiated methadone solely administered at opioid treatment programs, and 33,553 (67.5%) initiated buprenorphine primarily prescribed at office-based clinics. Compared with buprenorphine, initiation of methadone was associated with lower adjusted incidence rates of pain-related hospitalization (IRR, 0.64 (95% CI [0.58, 0.70]; P < .001); aRD, -7.2 (95% CI [-8.8 to -5.7]) per 1,000 person-years) and ED visit (IRR, 0.87 (95% CI [0.82, 0.92]; P < .001); aRD, -10.2 (95% CI [-14.4, -5.9]) per 1,000 person-years) in per-protocol analyses, with no difference in opioid overdose (IRR, 1.02 (95% CI [0.93,1.10]; P = .72); aRD, 0.33 (95% CI [-1.5, 2.1]) per 1,000 person-years) and all-cause mortality (HR, 1.06 (95% CI, [0.81-1.39]; P = .66); aRD, 1.1 (95% CI [-1.3, 1.0]) per 1,000 person-years) rates. Similar results were observed in intention-to-treat analyses. Main study limitations included unmeasured confounders and limited generalizability. CONCLUSIONS: This population-based cohort study of Medicare patients with comorbid chronic pain and OUD found that methadone administered at opioid treatment programs is associated with reduced hospitalizations and ED visits for pain-related visits while offering treatment outcomes similar to buprenorphine primarily prescribed at office-based clinics. The favorable pain-related outcomes in patients with methadone should be interpreted with caution, as the finding may reflect differences in the underlying patient population, treatment dosing practices, pharmacological properties, and treatment practice settings, which cannot be measured in Medicare data and merit further investigations.
Early aspirin withdrawal versus dual antiplatelet therapy in high-risk patients after percutaneous coronary intervention: Meta-analysis of randomized trials.
Navarese EP, Gurbel P, Tantry U … +10 more , Talanas G, Grzelakowska K, Umińska J, Jeong YH, Bliden K, Khan SU, Kubica J, Henry TD, Farkouh ME, Kereiakes DJ
PLoS Med · 2026 Mar · PMID 41886437 · Full text
BACKGROUND: Patients at high ischemic or bleeding risk after percutaneous coronary intervention (PCI) require protection against thrombotic events with dual antiplatelet therapy (DAPT) while avoiding bleeding. Although g...
BACKGROUND: Patients at high ischemic or bleeding risk after percutaneous coronary intervention (PCI) require protection against thrombotic events with dual antiplatelet therapy (DAPT) while avoiding bleeding. Although guidelines recommend 12-month DAPT after acute coronary syndrome (ACS), recent trials have tested the safety of early aspirin withdrawal with potent P2Y12-inhibitor monotherapy. METHODS AND FINDINGS: We performed a meta-analysis of randomized trials (from inception through August 2025) comparing early aspirin withdrawal (≤3 months) with transition to ticagrelor- or prasugrel-monotherapy versus continued DAPT. Co-primary outcomes were myocardial infarction (MI) and clinically relevant bleeding. Prespecified timing analyses stratified the comparison versus DAPT by aspirin timing: immediate (aspirin noninitiation or in-hospital cessation) and early (post-discharge discontinuation within 3 months). Bayesian models quantified risk-stratified probabilities of benefit and harm; trial sequential analysis (TSA) assessed conclusiveness of evidence. Seven trials (n = 27,743) were included. P2Y12-inhibitor monotherapy reduced bleeding (HR = 0.55, 95% CI [0.42, 0.71]; p < 0.001) without significantly increasing MI overall (HR = 1.11, 95% CI [0.91, 1.35]; p = 0.31), death, stroke, or stent thrombosis. Immediate aspirin noninitiation/cessation increased MI (HR = 1.41, 95% CI [1.01, 1.97]; p = 0.04), whereas early discontinuation did not (HR = 0.97, 95% CI [0.76, 1.24]; p = 0.82). TSA indicated conclusiveness for bleeding benefit and futility for an MI excess. Analyses restricted to ACS confirmed the overall results. Bayesian analyses corroborated these effects and identified risk-aligned timing: in high bleeding risk, ≤1-month aspirin discontinuation yielded a 100% posterior probability of bleeding benefit (NNT = 12) and 70% probability of MI-safety; in high ischemic risk, 3-month aspirin discontinuation yielded 100% probability of bleeding benefit (NNT = 57) and 86% probability of MI-safety. Limitations include aggregate data only and limited precision for the immediate aspirin withdrawal subgroup. CONCLUSIONS: Among high-risk post-PCI patients on ticagrelor/prasugrel, discontinuing aspirin within 3 months reduces bleeding without an ischemic trade-off versus DAPT. Immediate aspirin noninitiation or cessation should be avoided; timing should be individualized to bleeding and ischemic risk. PROSPERO: CRD420251167706.
Physical activity across mid-life and mortality outcomes in Australian women: A target trial emulation using a prospective cohort.
Nguyen B, Owen KB, Luo M … +4 more , Brown W, Mielke GI, Clare PJ, Ding D
PLoS Med · 2026 Mar · PMID 41886358 · Full text
BACKGROUND: Long-term causal evidence comparing different physical activity patterns and mortality outcomes is needed. Using observational data to emulate an RCT, this study compared different physical activity patterns...
BACKGROUND: Long-term causal evidence comparing different physical activity patterns and mortality outcomes is needed. Using observational data to emulate an RCT, this study compared different physical activity patterns over 15 years in relation to mortality from all causes, cardiovascular disease (CVD) and cancer in mid-aged Australian women. METHODS AND FINDINGS: A target trial emulation framework was used to emulate an RCT, based on data collected every 3 years (nine surveys between 1996 and 2019) from 11,169 women in the Australian Longitudinal Study on Women's Health (ALSWH; 1946-51 cohort). Two emulated interventions were compared against consistent non-adherence (control) to WHO moderate-to-vigorous physical activity (MVPA) recommendations during the 15-year 'exposure period': (1) consistent adherence to recommendations (at least 150 min/week) over 15 years (2001-2016; women were 50-55-65-70 years); and (2) starting to meet the recommendations at age 55, 60, or 65 years. Analyses were adjusted for sociodemographic and health variables using marginal structural models with the assumptions of conditional exchangeability, positivity, consistency, and no interference. Mortality outcomes that occurred between surveys 4-9 (women were 53-58 to 68-73 years), were ascertained from Australian death registries. Comparing consistent adherence to MVPA recommendations with consistent non-adherence, there was evidence (Bayes factor [BF] = 5.71) for a protective effect for all-cause mortality (risk ratio [RR]: 0.50, 99.5% CI [0.27, 0.94]; risk difference [RD]: -5.2%, 99.5% CI [-10.5%, 0.1%]). Findings for CVD (BF = 2.05; RR: 0.50, 99.5% CI [0.19, 1.30]; RD: -2.1%, 99.5% CI [-5.3%, 1.1%]) and cancer mortality (BF = 2.26; RR: 0.35, 99.5% CI [0.10, 1.17]; RD: -3.3%, 99.5% CI [-8.4%, 1.9%]) were more uncertain and less conclusive, as were those for an effect of starting to meet MVPA recommendations in the mid-fifties on mortality outcomes. The main study limitations included reliance of self-reported physical activity and that findings may not be generalisable to all mid-aged Australian women. CONCLUSIONS: Based on findings from this target trial emulation, women should be encouraged to meet physical activity recommendations throughout mid-age to derive mortality benefits.
Evaluating the biomedical and behavioral drivers of HIV incidence decline in adolescent girls and young women in Uganda: A mathematical modeling study.
Akullian A, Ssempijja V, Bridenbecker D … +19 more , Nalugoda F, Nakigozi G, Santelli J, Kreniske P, Chang LW, Reynolds SJ, Ssekubugu R, Gray RH, Wawer MJ, Quinn TC, Galiwango RM, Probert WJM, Imai-Eaton JW, Ratmann O, Fraser C, Kagaayi J, Kigozi G, Grabowski MK, Serwadda D
PLoS Med · 2026 Mar · PMID 41880347 · Full text
BACKGROUND: HIV incidence among adolescent girls and young women (AGYW) in eastern and southern Africa has declined substantially over the past two decades. These declines are often attributed to biomedical HIV preventio...
BACKGROUND: HIV incidence among adolescent girls and young women (AGYW) in eastern and southern Africa has declined substantially over the past two decades. These declines are often attributed to biomedical HIV prevention strategies, though concurrent changes in sexual behavior may also contribute. We evaluated the contributions of biomedical and behavioral drivers to historical incidence decline in AGYW and projected their impact on incidence trajectories over the next 30 years. METHODS AND FINDINGS: We conducted a mathematical modeling study using data from the Rakai Community Cohort Study (RCCS), an open, population-based cohort of adults aged 15-49 years in 30 communities in Rakai, Uganda. We used an agent-based HIV-1 transmission model calibrated to cohort data to estimate HIV incidence trends among AGYW, aged 15-24, and to quantify the independent and combined effects of antiretroviral therapy (ART), voluntary medical male circumcision (VMMC), and changes in age at first sex (AFS). HIV incidence among women aged 15-24 declined by 71% between 2000 and 2019, from 1.57 to 0.45 per 100 person-years, representing the largest decline across female age groups in the cohort. Increasing AFS over the study period (by approximately 3 years in women and 2 years in men) was the largest contributor to incidence declines among adolescent women aged 15-19, averting 17% of cumulative infections between 2000 and 2020 and 37% between 2000 and 2050. Among women aged 20-24, ART scale-up had the greatest impact, averting 13% of infections by 2020 and 43% by 2050. VMMC contributed modestly to historical declines but had larger projected effects over longer time horizons. ART, VMMC, and delays in AFS acted additively to reduce HIV incidence among AGYW. Study limitations include reliance on self-reported sexual behavior and the use of a mathematical model that cannot capture all real-world sexual network dynamics. CONCLUSIONS: Both biomedical HIV interventions and broader behavioral changes contributed to declines in HIV incidence among AGYW. Sustaining continued incidence declines in young women will require maintaining both the protective changes in sexual behaviors and effective biomedical interventions.
Transformer-based deep learning model for real-time prediction of intraoperative hypotension using dynamic time-series vital signs: A retrospective study.
Zhu S, Shi W, Qian H … +4 more , Tong X, Hu R, Bo J, Gu X
PLoS Med · 2026 Mar · PMID 41880331 · Full text
BACKGROUND: The clinical importance of transient intraoperative hypotension (IOH) remains debated, and existing models often rely on high-resolution waveform data that are not routinely available. METHODS AND FINDINGS: W...
BACKGROUND: The clinical importance of transient intraoperative hypotension (IOH) remains debated, and existing models often rely on high-resolution waveform data that are not routinely available. METHODS AND FINDINGS: We developed a Transformer-based deep learning model to predict IOH in real time using continuous vital sign time-series data. The model was trained on 319,699 surgical cases from a tertiary hospital in China (2013-2023) and externally validated using an independent dataset from South Korea. Model interpretability was explored through a real-time alert simulation using 10 representative surgical cases from the internal validation cohort, comparing predicted IOH risk trajectories with measured mean arterial pressure (MAP). To assess clinical relevance, a nested cohort study evaluated the association between IOH burden (cumulative MAP ≤65/60/55 mmHg in mmHg·min) and postoperative acute kidney injury (AKI) and acute kidney disease (AKD). The Transformer model achieved strong prediction performance at 5-, 10-, and 15-min horizons (AUCs 0.904, 0.892, 0.882; recall ≥88.3%). Compared with XGBoost, the Transformer had higher recall (internal 5-min recall 0.891 versus 0.737) and substantially better probability calibration (expected calibration error 0.0083 versus 0.0373). XGBoost showed higher overall accuracy and specificity (internal 5-min specificity 0.913 versus 0.723). External validation confirmed comparable discrimination across models and generalizability, with attenuated calibration differences. In alert simulations, predicted IOH risk closely corresponded to MAP fluctuations. IOH burden was significantly associated with postoperative AKI and AKD (MAP ≤65 mmHg: OR per 60 mmHg·min 1.10 (95% CI, [1.02, 1.19]; p = 0.012) for AKI; 1.26 (95% CI, [1.19, 1.33]; p < 0.001) for AKD). The study is limited by its retrospective design, and prospective, multicenter validation is needed to confirm real-time applicability and generalizability of the model. CONCLUSIONS: IOH burden is associated with increased risk of postoperative AKI and AKD. The Transformer model prioritizes sensitivity and calibration for short-term IOH prediction, whereas XGBoost emphasizes accuracy and specificity, reflecting different operating characteristics. Prospective, real-time evaluation is needed before clinical implementation.
Reassessing BMI-based access to joint replacement surgery.
Evans JP, McLaughlin J, Evans JT
PLoS Med · 2026 Mar · PMID 41875128 · Full text
Joint replacement surgery transforms lives for patients with higher body mass index (BMI). Strong evidence shows safe outcomes and meaningful benefit, yet access remains restricted by BMI alone, an approach that risks st...
Joint replacement surgery transforms lives for patients with higher body mass index (BMI). Strong evidence shows safe outcomes and meaningful benefit, yet access remains restricted by BMI alone, an approach that risks stigma, inequity, and avoidable harm.
The role of noninfectious comorbidities in the association between severe infections and risk of dementia in Finland: A nationwide registry study.
Sipilä PN, Korhonen K, Lindbohm JV … +2 more , Kivimäki M, Martikainen P
PLoS Med · 2026 Mar · PMID 41875076 · Full text
BACKGROUND: Severe infections have been linked to an increased risk of dementia, but both conditions often coexist with other illnesses that may confound this association. Using nationwide Finnish health registry data, w...
BACKGROUND: Severe infections have been linked to an increased risk of dementia, but both conditions often coexist with other illnesses that may confound this association. Using nationwide Finnish health registry data, we examined the role of noninfectious mental and physical illnesses in the association between severe infections and dementia. METHODS AND FINDINGS: This register-based study included 62,555 individuals aged 65 or older in Finland in 2016 who were diagnosed with late-onset dementia between 2017 and 2020 and 312,772 dementia-free controls matched for year of birth, sex, and the follow-up period. Analyses were adjusted for education, marital status, employment, and area of residence, with age and sex accounted for through the matched conditional design and analysis. Applying a 1-year lag period, we identified 29 hospital-treated diseases that occurred 1-21 years before dementia diagnosis in cases (or index date in controls), had a prevalence of ≥ 1% prior to dementia, and were robustly associated with increased dementia risk (confounder-adjusted rate ratio ≥ 1.20, p < 0.000294). In addition to 2 infectious diseases (cystitis and bacterial infection of an unspecified site), these included 27 mental, behavioural, digestive, endocrine, cardiometabolic, neurological, and eye diseases, as well as injuries. 29,376 (47%) of the dementia cases had at least one of these diseases diagnosed before dementia. The associations between the two infectious diseases and dementia risk were not attributable to the 27 comorbid dementia-related diseases diagnosed before infections. The adjusted rate ratio for cystitis was 1.22 (95% confidence interval (CI) [1.17, 1.27]; p < 0.001) before and 1.19 (95% CI [1.14, 1.24]; p < 0.001) after adjustment for comorbidities, while for bacterial infections of an unspecified site, the rate ratios were 1.21 (95% CI [1.16, 1.28]; p < 0.001) and 1.19 (95% CI [1.13, 1.25]; p < 0.001), respectively. The findings were comparable across subgroups defined by sex and education, and stronger for cases of early onset dementia. We were not able to directly assess psychosocial, behavioural, or biological confounders that are not captured in nationwide registries. CONCLUSIONS: This nationwide Finnish study identified several mental and physical diseases that are associated with an increased risk of dementia and showed that the increased incidence of dementia among individuals with severe infections is not attributable to these comorbid conditions. These results support the role of severe infections as independent risk factors for dementia.
Correction: How can middle-income countries successfully transition away from international health aid?
Ogbuoji O, Bharali I, Nonvignon J … +1 more , Yamey G
PLoS Med · 2026 Mar · PMID 41871019 · Full text
[This corrects the article DOI: 10.1371/journal.pmed.1004794.].
[This corrects the article DOI: 10.1371/journal.pmed.1004794.].
Association between COVID-19 vaccination and sudden death in apparently healthy younger individuals: A population-based case-control study.
Abdel-Qadir H, Bhatt HA, Swayze S … +4 more , Paterson M, Ko DT, Juurlink DN, Kwong JC
PLoS Med · 2026 Mar · PMID 41855201 · Full text
BACKGROUND: COVID-19 vaccines can cause rare but serious adverse events such as myocarditis and immune thrombotic thrombocytopenia. Despite a lack of strong evidence, concerns have been expressed that COVID-19 vaccinatio...
BACKGROUND: COVID-19 vaccines can cause rare but serious adverse events such as myocarditis and immune thrombotic thrombocytopenia. Despite a lack of strong evidence, concerns have been expressed that COVID-19 vaccination might lead to sudden death in younger healthy adults. We studied the association between COVID-19 vaccination and sudden death in apparently healthy people aged 12-50 years. METHODS AND FINDINGS: We conducted a population-based case-control study using linked administrative datasets of residents of Ontario, Canada who were alive as of April 1, 2021. We excluded individuals aged >50 years and those with documented cardiovascular disease, mental illness, or diseases that predispose to adverse outcomes from COVID-19. We defined cases as those with out-of-hospital death, or death within 24 hours of presentation to hospital with a final diagnosis of cardiac arrest between April 1, 2021 and June 30, 2023. We matched each case with five controls on age, sex, region of residence, and neighborhood income quintile. We used conditional logistic regression to assess the association between sudden death and previous COVID-19 vaccination after adjusting for multiple potential confounders (positive severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] tests, number of SARS-CoV-2 polymerase chain reaction (PCR) tests, influenza vaccination, common comorbidities). Sensitivity analyses were conducted with different definitions of the exposure and subsets of cases (with their matched controls). Another sensitivity analysis utilized a modified self-controlled case series (SCCS) of vaccinated individuals meeting the case definition during the study period with up to three doses of any COVID-19 vaccine. Of 6,365,451 eligible individuals, we identified 4,963 (0.08%) cases meeting our definition of sudden death (median age 36 years, 74.4% male). In the primary analysis, COVID-19 vaccination was associated with a lower risk of sudden death (adjusted odds ratio [aOR] = 0.57; 95% confidence interval (CI) [0.53,0.61]; p < 0.001). The findings were consistent for COVID-19 vaccination within six weeks before death (aOR = 0.63; 95%CI [0.55,0.72]; p < 0.001) and in sensitivity analyses limited to people aged <40 years (aOR = 0.53; 95%CI [0.48,0.58]; p < 0.001), those who died in hospital or in the emergency department (aOR = 0.71; 95%CI [0.55,0.91]; p = 0.006), and after exclusion of opioid-related deaths (aOR = 0.57; 95%CI [0.51,0.64]; p < 0.001). The SCCS sensitivity analysis showed no significant difference in the rate of sudden death in the 6 weeks following first (relative incidence (RI) 0.87; 95%CI [0.54,1.40]; p = 0.57), second (RI 0.94; 95%CI [0.57,1.57]; p = 0.82), or third (RI 0.87; 95%CI [0.37,2.05]; p = 0.10) dose of the COVID-19 vaccine. Study limitations include the inability to confirm the cause of out-of-hospital deaths and residual confounding due to differences in health-seeking behaviors for the case-control analysis. CONCLUSIONS: These findings do not support the hypothesis that COVID-19 vaccines increase the risk of sudden cardiac death in young healthy adults.
Estimating population immunity against serotype-two poliomyelitis from the inactivated polio vaccine in routine immunization across 112 countries: A modelling study.
Gray EJ, Cooper LV, Gonzalez AR … +4 more , Mach O, Derqui N, Grassly NC, Blake IM
PLoS Med · 2026 Mar · PMID 41855197 · Full text
BACKGROUND: To mitigate the risk of outbreaks of serotype 2 poliomyelitis after withdrawal of this serotype from oral poliovirus vaccine (OPV) in 2016, inactivated poliovirus vaccine (IPV) was introduced into the routine...
BACKGROUND: To mitigate the risk of outbreaks of serotype 2 poliomyelitis after withdrawal of this serotype from oral poliovirus vaccine (OPV) in 2016, inactivated poliovirus vaccine (IPV) was introduced into the routine immunization (RI) programmes of all countries using OPV. Since 2022, WHO has recommended a 2-dose schedule, with a first dose at 14 weeks of age followed by a second dose at least 4 months later (e.g., 14-39 week schedule), although an earlier schedule may be adopted, despite lower immunogenicity, if vaccine coverage is low at older ages. METHODS AND FINDINGS: We combined published data on type-2 IPV seroconversion with age, national RI coverage estimates, dose introduction dates, and country-specific schedules using a cohort model of population immunity to estimate IPV-induced immunity from 2024-2031 for 112 countries using either one or two doses of IPV. We projected immunity for current, 6-14, and 14-39 week schedules to find the optimal schedule and estimate the impact of interventions such as schedule changes and catch-ups. Under current schedules, estimated median serotype 2 population immunity in 2025 among children under five years of age is at 61% (IQR: 52%, 72%), rising to 71% (IQR: 57%, 80%) in 2031. The later 14-39 week schedule was optimal in all countries, with potential for the median immunity to rise to 78% (IQR: 66%, 85%) by 2031 if adopted by all countries in 2026. Eight countries would still have <50% immunity, rising to 65%-72% if catch-up campaigns with 80% coverage were implemented in 2030. The work is limited by the fact that IPV provides only a partial picture of total immunity where there has been emergency type-2 OPV use. Furthermore, national estimates may mask subnational coverage differences and pockets of extremely low immunity. CONCLUSIONS: Under these estimates, IPV schedules and coverage are suboptimal in many countries. Those with a single dose should introduce a second on the 14-39 week schedule; those on early schedules would benefit from adopting the 14-39 week schedule. IPV catch-up campaigns are recommended where RI coverage is low.
Circulating gut microbial metabolites and risk of coronary heart disease: A prospective multi-stage metabolomics study.
Zheng Y, Yang JJ, Gupta DK … +11 more , Herrington DM, Yu B, Nguyen NQH, Pinto R, Tzoulaki I, Cai H, Cai Q, Lipworth L, Shu XO, Zheng W, Yu D
PLoS Med · 2026 Mar · PMID 41843497 · Full text
BACKGROUND: Despite growing evidence linking gut microbiota and microbial metabolites to human cardiometabolic health, few studies have systematically examined associations between circulating microbial metabolites and i...
BACKGROUND: Despite growing evidence linking gut microbiota and microbial metabolites to human cardiometabolic health, few studies have systematically examined associations between circulating microbial metabolites and incident coronary heart disease (CHD). METHODS AND FINDINGS: We conducted a multi-stage metabolomics study involving five prospective cohorts. Discovery involved untargeted plasma metabolite profiling of 896 incident cases and 896 age-/sex-/race-matched controls (~300 pairs per race: Black, White, Asian) from the Southern Community Cohort Study (SCCS; baseline: 2002-2009) and the Shanghai Women's Health Study and Shanghai Men's Health Study (SWHS/SMHS; baseline: 1996-2000 and 2002-2006). In-silico validation was conducted in the Atherosclerosis Risk in Communities Study (ARIC; N = 3,539; 663 cases; baseline: 1987-1989) and Multi-Ethnic Study of Atherosclerosis (MESA; N = 3,860; 446 cases; baseline: 2000-2002). Lastly, a quantitative assay was developed and applied to a new set of 864 cases and 864 age-/sex-/race-matched controls (~260-340 pairs per race) from the SCCS and SWHS/SMHS. Conditional logistic regression estimated odds ratios (ORs) of incident CHD per standard deviation (SD) metabolite increase in discovery and quantitative stages with a nested case-control design. Cox regression was used in ARIC and MESA with a cohort design. Similar covariates were adjusted across stages, including age, sex (if applicable), race (if applicable), education, income, smoking status, alcohol consumption, physical activity, diet quality, and body mass index (BMI). The mean (SD) time between enrollment and CHD diagnosis was 5.6 (3.8), 6.9 (4.4), 15.0 (7.4), and 8.0 (4.9) years in the SCCS, SWHS/SMHS, ARIC, and MESA, respectively. The discovery stage identified 73 circulating microbiota-related metabolites associated with incident CHD (false discovery rate <0.10). Sixty-one metabolites were available for in-silico validation, of which 24 showed a significant association (p < 0.05) in the same direction as in the discovery. The targeted assay quantified eight of the 24 metabolites, with five significantly associated with incident CHD: imidazole propionate, 3-hydroxy-2-ethylpropionate, 4-hydroxyphenylacetate, trans-4-hydroxyproline, and 3-hydroxybutyrate; OR per SD ranged from 1.18 to 1.27 after adjustment for sociodemographics, lifestyles, and BMI. The targeted assay measured eight other promising microbial metabolites, four of which were significant: trimethylamine N-oxide, phenylacetyl-L-glutamine, 4-hydroxyhippuric acid, and indolepropionate. Most associations were consistent across participant subgroups by demographics, lifestyles, metabolic disease history, family CHD history, and follow-up time, although some potential effect modifications were found by race, age, obesity status, and follow-up time. The main limitations of the study are the observational design and the inability to validate all significant metabolites due to differences in metabolomic assay coverage across the three stages. CONCLUSIONS: We identified and validated circulating gut microbial metabolites associated with incident CHD across diverse populations. Our findings offer novel epidemiological evidence on the importance of gut microbial metabolism in CHD development and highlight specific metabolites to prioritize for mechanistic investigation, biomarker validation, and therapeutic development.
Living to our full potential: Reassessing global sex inequalities in life expectancy.
Weber AM, Darmstadt GL
PLoS Med · 2026 Mar · PMID 41843494 · Full text
Benchmarking life expectancy against what is achievable reveals how sex disadvantage shifts by age, place, and time, and reframes inequality as unrealized potential due to social and structural constraints rather than di...
Benchmarking life expectancy against what is achievable reveals how sex disadvantage shifts by age, place, and time, and reframes inequality as unrealized potential due to social and structural constraints rather than differences in biology.
Gene-environment equivalence: The fundamental principle of Mendelian randomization.
Davey Smith G, Hemani G, Ebrahim S
PLoS Med · 2026 Mar · PMID 41824471 · Full text
The explosion of Mendelian Randomization (MR) submissions of dubious quality to journals globally is well recognized. Contributing to this deluge of publications may be the poor understanding among practitioners, reviewe...
The explosion of Mendelian Randomization (MR) submissions of dubious quality to journals globally is well recognized. Contributing to this deluge of publications may be the poor understanding among practitioners, reviewers, and editors of gene-environment equivalence, the fundamental principle of MR.
The association between power outages and cardiovascular and respiratory hospitalizations among US Medicare beneficiaries in 2018: A case-crossover study.
McBrien H, Mork D, Do V … +2 more , Kioumourtzoglou MA, Casey JA
PLoS Med · 2026 Mar · PMID 41818642 · Full text
BACKGROUND: In the United States, already-prevalent power outages are increasing in frequency and duration with climate change. Studies from New York State show that power outages may increase hospitalizations for cardio...
BACKGROUND: In the United States, already-prevalent power outages are increasing in frequency and duration with climate change. Studies from New York State show that power outages may increase hospitalizations for cardiovascular disease (CVD) and respiratory disease in vulnerable populations such as older adults, but exposure data limitations have constrained nationwide studies of power outages and health. Here, we tested if power outages were associated with emergency CVD and respiratory disease-related hospitalizations among older adults in the United States. METHODS AND FINDINGS: We developed a national dataset of power outage exposure and identified county-days with ≥1% of customers exposed to 8+ hour power outages in 2018. We leveraged data on 23 million Medicare Fee-For-Service beneficiaries aged 65+ to estimate daily county-level rates of emergency CVD- and respiratory-related hospitalizations. We applied a case-crossover design with a conditional Poisson model to estimate the lagged association (up to 1 week) between daily county-level power outage exposure and cause-specific hospitalization rates. Models controlled for daily temperature, precipitation, and wind speed. RESULTS: Power outages were associated with increased emergency CVD and respiratory hospitalizations. The association between power outage and CVD hospitalizations was strongest the day after power outage exposure (rate ratio [RR]=1.02, 95% CI: 1.01, 1.03), while the association between outage and respiratory disease was strongest the day of power outage exposure (RR = 1.03, 95% CI: 1.01, 1.04). We estimated this association using county-level power outage data; future studies could use higher spatial resolution data. CONCLUSIONS: Power outages may increase the risk of CVD and respiratory hospitalizations among US older adults. Improving electricity reliability could support community health and protect older adults from CVD and respiratory disease exacerbations.
Quantify unmet medical need across the disease landscape - A large language model-based methodology.
Sharp EW, Fragola N, Blewitt C … +4 more , Goddeeris M, Lancashire L, Hempstead C, Fajgenbaum DC
PLoS Med · 2026 Mar · PMID 41818305 · Full text
BACKGROUND: Despite the ultimate goal of medical researchers and funders being to maximize patient benefit, there is no systematic process for quantifying unmet medical need across diseases. While a relative unmet medica...
BACKGROUND: Despite the ultimate goal of medical researchers and funders being to maximize patient benefit, there is no systematic process for quantifying unmet medical need across diseases. While a relative unmet medical need scoring system would be valuable for prioritization of medical research, systematically performing this effort across all 22,701 human diseases is technically challenging, time-consuming, and expensive. Using a large language model-based (LLM) architecture, we built a scalable method demonstrating feasibility to quantify "unmet medical need" criteria across all diseases, combine those criteria into a single weighted score, and extend the method into new criteria or diseases in the future. We aimed to quantitatively determine which diseases have the greatest unmet medical need and, therefore, which diseases are priority targets for new repurposed treatments. METHOD AND FINDINGS: We defined 11 scoring criteria across three categories of unmet medical need. For each criterion, we tested LLM models and refined prompts to generate a score per criteria for each disease and then defined a weighting for each criterion to contribute to a final score. A 30-disease development set was used to iterate on the prompting, and a 10-disease evaluation set was held out and used to evaluate the performance of the final prompt. All 22,701 human diseases in the MONDO disease ontology were quantitatively scored for their unmet medical need across all 11 weighted criteria. The resulting scores allowed for relative comparison between diseases of unmet medical needs. Inter-expert agreement was strong, indicating reliability of the scoring framework with 95% of ratings within a 1-point difference. Across multiple LLMs, gpt-4o is most closely aligned with expert rankings, achieving low mean and standard deviation differences relative to human scores. Furthermore, LLM-generated scores demonstrated strong Spearman's rho correlations with expert assessments across key clinical criteria, such as mortality (ρ = 0.845) and quality-adjusted life years lost (ρ = 0.822), supporting their suitability for prioritizing unmet medical need. All data were generated in ~1 hour with no missing data, at a total cost of $120 USD of compute and the results of the Unmet Medical Need Index are publicly available. The main limitation of this study is the combined size of the development and evaluation set being 40 diseases. CONCLUSIONS: This accessible, scalable methodology enables funders and researchers, across governments, universities, healthcare organizations, and disease groups to tailor prioritization efforts according to unmet medical need in the context of their organizational objectives, by selecting appropriate criteria and weighting of those criteria. This method creates a pragmatic and transparent tool to streamline research prioritization. Future research should consider expanding the disease set size used to create scores.
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