PLoS Med. [JOURNAL]
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200 papers
Clinical potential and challenges of spatially profiling tumor-infiltrating lymphocytes in early-stage breast cancer.
Page DB, Simanonok M, Hanes DA … +1 more , Su A
PLoS Med · 2026 Mar · PMID 41805747 · Full text
Digitally automated spatial profiling of immune-tumor cell interactions using multispectral immunofluorescence holds promise as a biomarker to predict outcomes in early-stage breast cancer, but prospective validation and...
Digitally automated spatial profiling of immune-tumor cell interactions using multispectral immunofluorescence holds promise as a biomarker to predict outcomes in early-stage breast cancer, but prospective validation and harmonization with existing biomarkers is necessary before clinical adoption.
Oral preexposure prophylaxis use and the risk of bacterial sexually transmitted infections and HIV among African women: A prospective observational cohort study.
Mukasa D, Kinuthia J, Meisner A … +15 more , Matemo D, Schaafsma T, Morton J, Wandera C, Budiawan E, Kemuto V, Irine C, Odhiambo S, Bii M, Oduor B, Achieng E, Oyombra T, Ukah UV, Mugwanya KK, FP Plus Project Team
PLoS Med · 2026 Mar · PMID 41802176 · Full text
BACKGROUND: Oral preexposure prophylaxis (PrEP) effectively reduces HIV incidence when used with sufficient adherence, but does not protect against bacterial sexually transmitted infections (STIs). Several studies have d...
BACKGROUND: Oral preexposure prophylaxis (PrEP) effectively reduces HIV incidence when used with sufficient adherence, but does not protect against bacterial sexually transmitted infections (STIs). Several studies have documented high rates of bacterial STIs among individuals initiating and using PrEP. We evaluated the association between PrEP use and the risk of STI among African women accessing family planning clinics. METHODS AND FINDINGS: We conducted a prospective cohort study nested within a large pragmatic stepped-wedge cluster randomized trial of PrEP delivery in Kenyan family planning clinics, with participant enrollment from June 18, 2021, to May 18, 2023, and follow-up through February 02, 2024 (ClinicalTrials.gov: NCT04666792). The study population included sexually active HIV-negative women aged ≥15 years at elevated HIV risk per Kenyan PrEP guidelines. Participants were offered standard-of-care oral PrEP with the option to decline and followed quarterly for 12 months with assessments of HIV status, sexual behavior, and PrEP use. Urine samples were batch tested for Neisseria gonorrhoeae and Chlamydia trachomatis using the GeneXpert CT/NG real-time polymerase chain reaction nucleic acid amplification test assay. The primary exposure was self-reported PrEP initiation and PrEP use consistency through 6 months, categorized as never used PrEP, inconsistently on PrEP, or consistently on PrEP. Multivariable modified Poisson generalized estimating equation (GEE) models with robust standard errors were used to estimate associations between PrEP use and incident STI; clinic-level intracluster correlation coefficients were negligible. The secondary outcomes were incident HIV infection and sexual behaviors, which included condomless sex at last sex, sex with any new partners in the past 3 months, and multiple sex partners. HIV testing was performed at each scheduled visit, at enrollment, and 1, 3, 6, 9, and 12 months following the Kenya national HIV testing algorithm, using Determine HIV-1/2 and Fast Response test kits. All models for the primary outcome were adjusted for baseline covariates determined apriori as potential confounders, which included age, STI diagnosis at enrollment, any contraceptive use, number of sexual partners (categorized as any more than one sexual partner), education status, marital status, last partner HIV status, any transactional sex in 3 months pre-enrollment, and clinic site. Among 650 women enrolled, 60.0% (389) initiated PrEP at baseline and 14.6% (38/261) initiated post-enrollment. Median age was 26 years (IQR 23-30), 40% (262/650) were aged ≤24 years, and 67% (436/648) did not know their primary partner's HIV status. At baseline, 11% (74/650) had an STI, including 9.9% (23/232) of consistent PrEP users, 9.2% (13/141) of inconsistent users, and 14.0% (38/277) of women who declined PrEP. During follow-up, 19.1% (114/597) had at least one STI diagnosis, with similar risk among women who initiated PrEP at baseline compared with those who declined (19.2% [68/354] versus 18.9% [46/244]; aRR 1.11, 95% CI 0.76-1.61; p = 0.580). Compared with non-PrEP users (12.7% [25/195]), STI risk was 6.0% (12/200) among consistent PrEP users (aRR 0.56, 95% CI 0.27-1.19; p = 0.130) and 16.5% (17/103) among inconsistent users (aRR 1.43, 95% CI 0.73-2.77; p = 0.290). Chlamydia accounted for 87.7% (100/114) of STI diagnoses. STI risk was higher among women aged ≤24 years (aRR 1.47, 95% CI 1.04-2.07; p = 0.029) and those with a baseline STI (aRR 2.96, 95% CI 2.12-4.14; p < 0.001). Four HIV infections occurred over 594 person-years (incidence 0.67, 95% CI 0.18-1.72 per 100 person-years), including three among women who declined PrEP (incidence 1.25, 95% CI 0.26-3.66 per 100 person-years). The main study limitation was oral PrEP use was assessed based on client self-report and not objectively through drug levels testing. CONCLUSIONS: In this prospective cohort study among African women at elevated risk for HIV, 60% initiated PrEP at baseline and 14.6% (38/261) post-enrollment. PrEP use was not associated with increased risk for STI diagnosis through one year of follow-up. HIV incidence was low overall, consistent with expanded PrEP availability in similar populations.
SGLT2 inhibitors, GLP-1 RAs, and DPP4 inhibitors and the risk of hypomagnesemia in type 2 diabetes: A target trial emulation.
Shao SC, Tsai DH, Chuang AT … +2 more , Liu KH, Lai EC
PLoS Med · 2026 Mar · PMID 41790761 · Full text
BACKGROUND: Recent studies have suggested potential effects on magnesium homeostasis associated with sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RA). We sought t...
BACKGROUND: Recent studies have suggested potential effects on magnesium homeostasis associated with sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RA). We sought to determine whether these effects lead to a reduced risk of hypomagnesemia among adults with type 2 diabetes in clinical practice. METHODS AND FINDINGS: We conducted a target trial emulation study using the multi-institutional cohort data from the TriNetX Global Collaborative Network. We compared 1:1 propensity score-matched patients with type 2 diabetes newly initiating SGLT2 inhibitors versus dipeptidyl peptidase-4 (DPP4) inhibitors (n = 718,798), GLP-1 RAs versus DPP4 inhibitors (n = 623,390), and SGLT2 inhibitors versus GLP-1 RAs (n = 702,808) from 2016 to 2024. Propensity scores were estimated using logistic regression models that included baseline covariates such as age, sex, race, comorbidities, and medication and laboratory data. In each comparison, patients receiving DPP4 inhibitors were considered the active-comparator group. The primary outcome was incident hypomagnesemia, defined by clinical diagnosis or serum magnesium <1.80 mg/dL. Patients were followed until the occurrence of an outcome of interest, last clinical visit, death, or the end of database period (March 31, 2025), whichever came first. We found that initiation of SGLT2 inhibitors was associated with a significantly lower risk of hypomagnesemia, compared with both DPP4 inhibitors (Hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.79, 0.82; p < 0.05) and GLP-1 RAs (HR: 0.92; 95% CI: 0.91, 0.93; p < 0.05). Similarly, GLP-1 RA use was associated with a lower risk of hypomagnesemia, compared with DPP4 inhibitors (HR: 0.89; 95% CI: 0.88, 0.91; p < 0.05). These associations were consistent across individual agents within each drug class. The main limitation of our study is that residual confounding inherent to retrospective observational research cannot be completely ruled out. CONCLUSIONS: Treatment with SGLT2 inhibitors and GLP-1 RAs was associated with a lower risk of hypomagnesemia, compared with DPP4 inhibitors. These findings suggest that SGLT2 inhibitors and GLP-1 RAs may be preferable options for patients at risk of hypomagnesemia.
Detrimental infant and maternal outcomes of undiagnosed asymptomatic malaria in pregnancy.
Beeson JG, Opi DH
PLoS Med · 2025 Feb · PMID 41789823 · Full text
In areas with low malaria transmission intensity, most infections during pregnancy are not detected by standard diagnostic tests. New data shows that these missed asymptomatic infections have substantial negative impacts...
In areas with low malaria transmission intensity, most infections during pregnancy are not detected by standard diagnostic tests. New data shows that these missed asymptomatic infections have substantial negative impacts for both the mother and the developing fetus.
Childhood cancer in Sweden during the COVID-19 pandemic: Temporal patterns in incidence and survival in a nationwide register-based cohort study.
Kampitsi CE, Louro J, Mogensen H … +7 more , Erdmann F, Georgantzi K, Heyman M, Lähteenmäki P, Nilsson A, Feychting M, Tettamanti G
PLoS Med · 2026 Mar · PMID 41785170 · Full text
BACKGROUND: The COVID-19 pandemic raised concerns about diagnostic delays and treatment disruptions in childhood cancer, potentially threatening survival. We assessed childhood cancer incidence and survival in Sweden, wh...
BACKGROUND: The COVID-19 pandemic raised concerns about diagnostic delays and treatment disruptions in childhood cancer, potentially threatening survival. We assessed childhood cancer incidence and survival in Sweden, where only few restrictions were implemented, during the pandemic period. METHODS AND FINDINGS: We conducted a nationwide, register-based cohort study including all children and adolescents (0-19 years) with a new cancer diagnosis, defined according to the International Classification of Childhood Cancer, Third Edition (ICCC-3), reported to the Swedish National Cancer Register during 2015-2022 (N = 3,333; 2,069 pre-pandemic and 1,264 during the pandemic). We compared quarter-specific age-standardized incidence rates (ASR) per 1,000,000 (overall and by diagnostic group) during 2020-2022 to the 2015-2019 average. Overall survival at 3, 6, and 12 months post-diagnosis was calculated using the Kaplan-Meier estimator, and mortality at the same intervals was assessed with logistic regression, adjusted for age at diagnosis, sex, and maternal education. Overall incidence rates remained largely stable during the pandemic (ASR2015-2019: 179.5; 95% CI [172.9,186.1], ASR2020: 174.7; 95% CI [160.5,189.0], ASR2021: 176.5; 95% CI [161.6,191.5], ASR2022: 181.2; 95% CI [166.3,196.2]), but diagnostic groups showed differing tendencies. Acute lymphoblastic leukemia (ALL) declined from February 2020, followed by a rebound in 2021. Acute myeloid leukemia (AML) declined throughout 2020-2022 without evidence of a rebound. Lymphomas declined in mid-2020 before returning to pre-pandemic levels. Central nervous system (CNS) tumors transiently increased in 2020. Overall 1-year survival was 94.8% (95% CI [93.9,95.8]) in the pre-pandemic period and 95.9% (95% CI [94.8,97.0]) during the pandemic. No increase in 6-month or 1-year mortality was observed; if anything, point estimates suggested lower 1-year mortality for ALL (aOR = 0.37; 95% CI [0.08,1.21]; p = 0.14) and CNS tumors (aOR = 0.61; 95% CI [0.31,1.14]; p = 0.13). The main limitation of this study was statistical uncertainty for certain diagnostic groups due to small case numbers. CONCLUSIONS: Overall childhood cancer incidence and survival in Sweden showed no major changes during the COVID-19 pandemic. Fluctuations in diagnostic-group-specific incidence may reflect delayed diagnoses or shifts in disease triggers; however, the timing of the ALL decline and the lack of AML rebound challenge this interpretation. Stable or improved survival suggests that any disruptions were not associated with poorer survival up to 1 year after diagnosis.
From crisis response to country control: Restoring agency and sustainability in global health.
Okereke E
PLoS Med · 2026 Mar · PMID 41774681 · Full text
Global health is at a structural inflection point. Crisis-driven architectures saved lives but entrenched fragility and dependence. Sustaining progress now requires restoring country agency, strengthening national instit...
Global health is at a structural inflection point. Crisis-driven architectures saved lives but entrenched fragility and dependence. Sustaining progress now requires restoring country agency, strengthening national institutions, and securing predictable, sustainable health financing.
From pain to policy: Improving endometriosis awareness, diagnosis, and treatment.
Tosun A, PLOS Medicine Staff Editors
PLoS Med · 2026 Mar · PMID 41770832 · Full text
Despite affecting 190 million women worldwide, endometriosis remains underdiagnosed, under-researched, and underfunded. Tackling awareness gaps, diagnostic delays, and inadequate treatment requires earlier education, inc...
Despite affecting 190 million women worldwide, endometriosis remains underdiagnosed, under-researched, and underfunded. Tackling awareness gaps, diagnostic delays, and inadequate treatment requires earlier education, increased funding, and recognition of endometriosis as a systemic disease-redefining pain, equity, and investment in women's health.
The genetic architecture of postoperative delirium after major surgery and its relationship with nonpostoperative neurocognitive conditions: A genome-wide association study.
Armstrong RA, Yousefi P, Gibbison B … +2 more , Khandaker GM, Gaunt TR
PLoS Med · 2026 Mar · PMID 41770756 · Full text
BACKGROUND: Postoperative delirium is the most common postoperative complication in older individuals. Genome-wide association studies (GWAS) can provide insights into how genetic factors influence postoperative risk. We...
BACKGROUND: Postoperative delirium is the most common postoperative complication in older individuals. Genome-wide association studies (GWAS) can provide insights into how genetic factors influence postoperative risk. We examined the genetic architecture of postoperative delirium after major surgery and its relationship with related cognitive conditions (delirium of any type and Alzheimer's disease, including the APOE ε4 allele). METHODS AND FINDINGS: A case-control GWAS was performed in the UK Biobank to identify genetic variants associated with postoperative delirium, adjusted for age, sex, genetic chip, and the first 10 principal components. These results were then used in genetic correlation and polygenic risk score analyses to investigate shared genetic risk between postoperative delirium and a) delirium of all causes, and b) Alzheimer's disease. The GWAS (1,016 cases, 139,148 controls) identified seven Single Nucleotide Polymorphisms (SNPs) that mapped to four genes (APOE, TOMM40, APOC1, and PVRL2); p < 5 x 10-8. Five SNPs remained significant after excluding pre-existing dementia, and two after excluding subsequent dementia. The lead SNP was rs429358, a missense variant of APOE. Genetic correlation and polygenic risk score analyses revealed evidence of shared genetic architecture and risk between postoperative delirium and Alzheimer's disease (rho 0.68, 95% CI [0.46, 0.81]; p < 0.001). After adjustment for age and sex, the APOE ε4 isoform had a dose-response effect on risk (odds ratios for one and two copies: 1.75, 95% CI [1.53, 2.0], and 4.19, 95% CI [3.25, 5.41], respectively; p < 0.001). The main limitations of the study include the reliance upon clinical coding for outcome definition and limited statistical power to detect small or modest genetic effects. CONCLUSIONS: We identified genetic variants associated with increased risk of postoperative delirium. We also found evidence of shared genetic liability with Alzheimer's disease via APOE, complementing recent large-scale studies in all-cause delirium. If validated, the findings have potential clinical applications, including preoperative risk stratification and early identification of pre-clinical Alzheimer's disease risk.
Better, not just fewer: Rethinking antibiotic prescribing.
Sulis G, MacFadden DR
PLoS Med · 2026 Feb · PMID 41758778 · Full text
Clinical decision support tools can curb unnecessary antibiotic use, but success depends on more than technology. Here, we explore behavioral, equity, and governance challenges in tackling antimicrobial resistance, and w...
Clinical decision support tools can curb unnecessary antibiotic use, but success depends on more than technology. Here, we explore behavioral, equity, and governance challenges in tackling antimicrobial resistance, and why "better, not just fewer" prescriptions are essential.
Reimagining care of people living with rare diseases with artificial intelligence.
Groza T, Baynam G, Jamuar SS
PLoS Med · 2026 Feb · PMID 41746939 · Full text
Artificial intelligence (AI) can transform rare disease care when organized around the patient journey. We outline a patient-clinician-AI triad spanning early detection, diagnosis, clinical trials, and individualized the...
Artificial intelligence (AI) can transform rare disease care when organized around the patient journey. We outline a patient-clinician-AI triad spanning early detection, diagnosis, clinical trials, and individualized therapies.
Medication adherence and its associated factors among oral pre-exposure prophylaxis (PrEP) users in China: The Real-world E-consumer Cohort of PrEP study.
Li Q, Zhou J, Xu Y … +13 more , Zou H, Lin C, Zhang M, Zheng J, Zhang Y, Huang S, Zhao Z, Ruan C, Cheng J, Xu J, Tang H, Xue H, Luo S
PLoS Med · 2026 Feb · PMID 41746930 · Full text
BACKGROUND: Medication adherence is the key to success of HIV pre-exposure prophylaxis (PrEP). In China, the majority of real-world users purchase PrEP through e-commerce platforms, yet their adherence remains unaddresse...
BACKGROUND: Medication adherence is the key to success of HIV pre-exposure prophylaxis (PrEP). In China, the majority of real-world users purchase PrEP through e-commerce platforms, yet their adherence remains unaddressed. This cohort study aimed to evaluate PrEP adherence and its associated factors among e-consumers in China. METHODS AND FINDINGS: Eligible participants who had purchased PrEP online in the past 3 months were enrolled in the Real-world E-consumer Cohort of PrEP (RECOPE) in December 2023. Anonymous self-administered e-questionnaires were used at baseline and 1-, 3-, and 6-month follow-ups to collect data on PrEP adherence and potentially associated factors. Optimal adherence was defined as full compliance with the '2-1-1' dosing protocol for event-driven (ED) users and no missed pills in the past month for daily users. Generalized linear mixed-effects models and logistic regression were fitted to identify prognostic factors of PrEP adherence. Of 877 individuals invited, 680 were eligible and 657 completed the baseline survey (response rate 96.6%). The follow-up response rate at the 1-, 3-, and 6-month timepoints was 90.1% (592/657), 82.6% (543/657), and 80.1% (526/657), respectively. Among the 621 participants who had initiated PrEP at baseline, 529 (85.2%) used the ED regimen, and 92 (14.8%) used the daily regimen. Among ED users, the prevalence of optimal adherence at the four timepoints was 41.3% (154/373), 43.1% (146/339), 45.3% (139/307), and 52.6% (160/304), respectively. Among daily users, the prevalence of optimal adherence was 83.7% (77/92), 81.4% (83/102), 87.8% (86/98), 84.3% (75/89) at each survey wave, respectively. Within this group, the mean adherence rates in the past month ranged from 97.1% to 98.7% across waves. Among ED users, older age, receptive or versatile sexual role, and higher self-efficacy were positively associated with optimal adherence, while multiple same-sex partners, chemsex, and PrEP-related stigma were negatively associated factors. Selection bias, recall bias, social desirability bias, confounding bias, and limited representativeness were the main limitations of the study. CONCLUSION: The study found PrEP adherence was low among ED PrEP users who account for the majority of real-world e-consumers in China. Targeted interventions are suggested to prioritize enhancing users' understanding of medication instructions, promoting self-efficacy of maintaining adherence, and alleviating PrEP-related stigma. Additional attention should be given to ED users who have chemsex, insertive anal sex, multiple sexual partners, or a younger age.
Effectiveness of a digital clinical decision support algorithm for guiding antibiotic prescribing in pediatric outpatient care in Rwanda: A pragmatic cluster non-randomized controlled trial.
Kulinkina AV, Rwandarwacu VP, Habakurama J … +14 more , Cobuccio L, Norris M, Kalisa E, Havugimana C, Ingabire A, Levine GA, Tan R, Faivre V, Vonlanthen A, Le Pogam MA, Wyss K, Tuyisenge L, Ngabonziza JCS, D'Acremont V
PLoS Med · 2026 Feb · PMID 41746877 · Full text
BACKGROUND: Poor adherence to clinical guidelines and diagnostic uncertainty are key contributors to antibiotic overprescription, accelerating antimicrobial resistance. We developed ePOCT+, a digital clinical decision su...
BACKGROUND: Poor adherence to clinical guidelines and diagnostic uncertainty are key contributors to antibiotic overprescription, accelerating antimicrobial resistance. We developed ePOCT+, a digital clinical decision support algorithm (previously published) that integrated oxygen saturation, hemoglobin measurements, and C-reactive protein testing to assist primary care clinicians in managing acutely ill children aged 14 years or below. The goal was to reduce antibiotic prescriptions without compromising clinical recovery. METHODS AND FINDINGS: We conducted a pragmatic, open-label cluster non-randomized controlled trial in 32 Rwandan health centers allocated to two groups by geography, balancing patient volume and infrastructure. Sixteen sites used ePOCT+ throughout; the other 16 provided standard care for five months before crossing over. This design supported three comparisons: intervention-control (months 1-5), before-after (control sites pre- versus post-crossover), and longitudinal assessment (intervention sites over 10 months). ePOCT+ was deployed in a digital application; the same application (without the algorithm) served as an electronic case report form in the control arm. Outcomes were analyzed using mixed-effects logistic regression, adjusted for age, sex, district, and presenting complaints. Superiority in antibiotic prescription (primary outcome) was defined as ≥25% reduction versus routine care. Non-inferiority for clinical failure (main secondary outcome) was defined as adjusted risk ratio upper 95% CI <1.3. Several other secondary outcomes were analyzed and reported. Between December 2021 and April 2023, 59,921 consultations were enrolled and 47,822 new consultations were analyzed. ePOCT+ uptake averaged 70% across all intervention periods. In the primary per-protocol analysis, antibiotic prescriptions declined from 70.5% to 24.5% in the intervention-control comparison (absolute difference -46.0, 95% CI [-52.5, -39.5]) and to 27.5% in the before-after comparison (absolute difference -43.0, 95% CI [-49.7, -36.4]). Reductions in the intention-to-treat sensitivity analysis were -36.7 (95% CI [-42.1, -31.3]) in the intervention-control comparison and -26.7 (95% CI [-32.2, -21.4]) in the before-after comparison, respectively. Prescription rates remained low (25%-40%) throughout the longitudinal assessment. Clinical failure rates were non-inferior (per-protocol aRR 1.07, 95% CI [0.97, 1.18] and 1.00, 95% CI [0.92, 1.10] in intervention-control and before-after analyses, respectively). In the intervention-control comparison, referral rates (aRR 2.11, 95% CI [1.20, 3.70]), primary hospitalizations (aRR 2.02, 95% CI [1.21, 3.38]), secondary hospitalizations (aRR 1.93, 95% CI [1.17, 3.16]), and severe outcomes (comprised primarily of non-referred secondary hospitalizations; aRR 1.88, 95% CI [1.11, 3.15]) were higher in the intervention arm; no differences were observed in the before-after comparison, suggesting possible baseline differences in patient severity rather than intervention effects. Re-attendance rates did not differ between arms. Malaria testing among febrile cases improved (aRR 1.27, 95% CI [1.08, 1.41]), while treatment adherence remained high. Study limitations included non-randomized design and self-reported outcomes. CONCLUSIONS: ePOCT+ substantially reduced antibiotic prescribing in Rwandan pediatric primary care without compromising clinical recovery. Integration into Rwanda's national electronic medical record platform is critical to ensure unified clinical and reporting functions. This could streamline service delivery, improve data quality, and promote evidence-based care at scale. TRIAL REGISTRATION: Clinicaltrials.gov NCT05108831.
The potential impact of reduced international donor funding on the household economic burden of tuberculosis in low- and middle-income countries: A modeling study.
Portnoy A, Clark RA, Jit M … +9 more , McQuaid CF, Richards AS, Bakker R, Sumner T, Prŷs-Jones TO, Houben RMGJ, White RG, Horton KC, Menzies NA
PLoS Med · 2026 Feb · PMID 41719377 · Full text
BACKGROUND: Recent shifts in the global health funding landscape-most notably the dismantling of the United States Agency for International Development (USAID) and possible reduced contributions to the Global Fund to Fig...
BACKGROUND: Recent shifts in the global health funding landscape-most notably the dismantling of the United States Agency for International Development (USAID) and possible reduced contributions to the Global Fund to Fight AIDS, TB, and Malaria (Global Fund)-threaten essential tuberculosis (TB) services in low- and middle-income countries (LMICs). We quantified the potential impact on the household economic burden of TB. METHODS AND FINDINGS: We used linked epidemiological and economic models, calibrated to 79 LMICs, to estimate future TB patient costs under six scenarios: continuation of 2024 funding levels (baseline), termination of USAID, termination of USAID plus announced reductions in Global Fund contributions from the USA alone, termination of USAID plus complete termination of Global Fund contributions from the USA alone, termination of USAID plus announced reductions in Global Fund contributions from all donor countries contributing 1% or more to the budget, and full elimination of external funding for TB. Outcomes included total TB-attributable household costs and numbers of households experiencing catastrophic costs (disease-related costs >20% of annual income). USAID termination was projected to produce US$7.5 (95% uncertainty interval: $6.1-8.9) billion in additional patient-incurred costs and 3.9 (3.1-4.6) million additional households experiencing catastrophic costs over 2025-2050. The worst-case scenario (elimination of all external funding) resulted in $79.7 ($60.0-99.2) billion in additional patient-incurred costs and 40.5 (30.9-50.7) million additional households experiencing catastrophic costs-a 32% increase over baseline. Impacts were greatest for poorer households, with over 50% of additional catastrophic costs occurring in the poorest 20% of households. This analysis is limited by substantial uncertainty regarding costs faced by untreated patients and assumptions of constant patient costs and uniform treatment reductions over time. CONCLUSIONS: Abrupt reductions in international donor funding for TB may reverse recent progress toward financial risk protection and health equity in LMICs. Strategies to reduce the disruption caused by funding cuts and protect vulnerable populations are urgently needed.
Health disparities in transitions between kidney replacement therapy modalities and mortality in England: A multistate model using UK Renal Registry data.
Potts J, Pearse CM, Lambie M … +8 more , Fotheringham J, Hill H, Coyle D, Damery S, Allen K, Williams I, Davies SJ, Solis-Trapala I
PLoS Med · 2026 Feb · PMID 41706754 · Full text
BACKGROUND: While ethnic and deprivation-related disparities in kidney replacement therapy (KRT) initiation are well established, their impact on transitions between treatment modalities and mortality over the course of...
BACKGROUND: While ethnic and deprivation-related disparities in kidney replacement therapy (KRT) initiation are well established, their impact on transitions between treatment modalities and mortality over the course of kidney failure remains poorly understood. This study aimed to examine the association between ethnicity and area-level deprivation and the rates of transition between treatment modalities and death across the patient life course on KRT. METHODS AND FINDINGS: We used a parametric multistate model to analyse UK Renal Registry data from 93,451 patients initiating KRT in England between 2005 and 2020 with a median follow-up of 1,497 days [IQR: 640-2,841] (4.1 years [IQR: 1.75,7.8]). We estimated transition-specific hazard rates and probabilities between peritoneal dialysis (PD), home haemodialysis (HHD), in-centre haemodialysis (ICHD), transplantation, and death using Weibull proportional hazard models. Ethnicity and area-level deprivation (measured by quintiles of the Index of Multiple Deprivation [IMD]) were included as covariates of primary interest, with models additionally adjusted for sex, age and diabetes mellitus as the primary kidney disease (PKD). Compared with White patients, Asian patients had lower transition rates from ICHD to PD (hazard ratio [HR]: 0.68, 95% confidence interval [CI] [0.51,0.91]), and from PD to ICHD (HR 0.85, 95% CI [0.78,0.92]), but a higher rate of returning to ICHD after transplantation (HR 1.12, 95% CI [1.01,1.24]). Black patients also had lower transition rates from ICHD to PD (HR 0.64, 95% CI [0.47,0.88]) and to HHD (HR 0.47, 95% CI [0.37,0.61]), but higher rates of transition from PD to ICHD (HR 1.16, 95% CI [1.01,1.33]) and from transplantation to ICHD (HR 1.73, 95% CI [1.44,2.08]). Patients living in the most deprived areas had lower transition rates from ICHD to PD (HR 0.63, 95% CI [0.56,0.70]), to HHD (HR 0.49, 95% CI [0.38,0.64]), and to transplantation (HR 0.57, 95% CI [0.52,0.64]), and higher rates from transplantation to ICHD (HR 1.63, 95% CI [1.43,1.85]) and to death (HR 1.53, 95% CI [1.33,1.76]), compared with those from the least deprived areas. A limitation of our study is that, apart from diabetes mellitus as the PKD, comorbidities were not included in the analysis due to incomplete reporting in the UK Renal Registry. This should be considered when interpreting the observed disparities, particularly those related to area-level deprivation. CONCLUSIONS: These findings highlight persistent inequalities throughout the KRT pathway. The multistate modelling framework applied in this study offers a foundation for future research to design and evaluate interventions that improve equity and patient outcomes in kidney care.
Can generative artificial intelligence enhance evidence-based and personalized medicine?
Thirunavukarasu AJ
PLoS Med · 2026 Feb · PMID 41701795 · Full text
Should clinical applications of generative artificial intelligence (GAI) be designed to follow treatment guidelines rigidly, provide individualized recommendations, or be somewhere in-between? A recent study in PLOS Medi...
Should clinical applications of generative artificial intelligence (GAI) be designed to follow treatment guidelines rigidly, provide individualized recommendations, or be somewhere in-between? A recent study in PLOS Medicine comparing GAI versus physician treatment recommendations highlights the importance of context- and patient-specific circumstances in decision-making.
The effect of prenatal balanced energy and protein supplementation on small vulnerable newborn types in low- and middle-income countries: A systematic review and meta-analysis of individual participant data.
Wang D, Partap U, Liu E … +32 more , Costa JC, Cliffer IR, Wang M, Nookala SK, Subramoney V, Briggs B, Ahmed I, Argaw A, Ariff S, Bhandari N, Chowdhury R, Dailey-Chwalibóg T, Hanley-Cook GT, Huybregts L, Jehan F, Krebs NF, Lachat C, Manandhar DS, McClure EM, Moore SE, Muhammad A, Nisar MI, Prentice AM, Roberfroid D, Saville NM, Shafiq Y, Shrestha BP, Sonko B, Soofi S, Taneja S, Toe LC, Fawzi WW
PLoS Med · 2026 Feb · PMID 41701774 · Full text
BACKGROUND: Small vulnerable newborn (SVN) types, defined by combinations of being born too soon or too small, have distinct determinants, health consequences, and prevention strategies. The effects of prenatal balanced...
BACKGROUND: Small vulnerable newborn (SVN) types, defined by combinations of being born too soon or too small, have distinct determinants, health consequences, and prevention strategies. The effects of prenatal balanced energy and protein (BEP) supplementation on SVN types remain unknown. METHODS AND FINDINGS: We conducted a systematic review and meta-analysis of individual participant data from eight randomized controlled trials of prenatal BEP supplements (N = 10,252, with 5,164 in the BEP arm and 5,088 in the control arm) in low- and middle-income countries were used. The control arms varied across studies and included context-specific standards of care, iron and folic acid supplements, or multiple micronutrient supplements. Newborns were classified into 10 groups through the combinations of preterm birth, small for gestational age (SGA) birth, and low birthweight (LBW), such as term-appropriate-for-gestational-age (AGA)-nonLBW, preterm-SGA-LBW, preterm-large-for-gestational-age-LBW, term-SGA-LBW, preterm-AGA-nonLBW, and other permutations. Newborns were also analyzed using a four-group categorization that included term-nonSGA, preterm-nonSGA, term-SGA, and preterm-SGA. Log-binomial models were used to estimate study-specific risk ratios (RRs), which were pooled using meta-analyses. Subgroup analyses were conducted by maternal age, parity, gestational age at enrollment, early pregnancy body mass index, and maternal anemia status. In the 10-group categorization of SVNs, on average, prenatal BEP supplementation led to a 30% lower risk of preterm-SGA-LBW (RR: 0.70; 95% CI [0.53, 0.91]; P = 0.009), a 25% lower risk of preterm-AGA-LBW (RR: 0.75; 95% CI [0.60, 0.93]; P = 0.009), and a 20% lower risk of term-SGA-LBW (RR: 0.80; 95% CI [0.72, 0.90]; P < 0.001). In the four-group categorization, prenatal BEP supplementation led to a 31% lower risk of preterm-SGA (RR: 0.69; 95% CI [0.52, 0.91]; P = 0.008) and a 12% lower risk of term-SGA (RR: 0.88; 95% CI [0.81, 0.96]; P = 0.005). The protective effect of prenatal BEP supplementation on preterm-SGA was stronger among multiparous women and women without anemia. The protective effects on all three SVN types under the four-group categorization were stronger among women enrolled before 20 weeks of gestation. The main limitations of the study included the absence of some BEP trials and the small event numbers for some SVN types. CONCLUSIONS: Prenatal BEP supplementation reduces the risk of SVNs to varying extents. Further research is needed to determine the optimal targeting approach for providing BEP supplements to vulnerable pregnant women who are most likely to benefit from the supplementation.
The role of comorbidities in the associations between air pollution and Alzheimer's disease: A national cohort study in the American Medicare population.
Deng Y, Liu Y, Hao H … +5 more , Xu K, Zhu Q, Li H, Ma T, Steenland K
PLoS Med · 2026 Feb · PMID 41701678 · Full text
BACKGROUND: Air pollution and several common comorbidities-such as hypertension, stroke, and depression-are established risk factors for Alzheimer's disease (AD). However, whether these comorbidities mediate or amplify t...
BACKGROUND: Air pollution and several common comorbidities-such as hypertension, stroke, and depression-are established risk factors for Alzheimer's disease (AD). However, whether these comorbidities mediate or amplify the effects of fine particulate matter (PM2.5) on AD remains unclear. We aimed to investigate whether these conditions modify or mediate the association between PM2.5 exposure and incident AD. METHODS AND FINDINGS: We conducted a nationwide cohort study including 27.8 million US Medicare beneficiaries aged 65 years and older from 2000 to 2018. Exposure to PM2.5 was assessed using high-resolution air pollution datasets. Cox proportional hazards models were applied to estimate the associations between exposure to PM2.5, incident AD, and comorbidities. The potential for comorbidities to modify and mediate the association between PM2.5 and AD was evaluated by stratified analyses and mediation analysis. We identified approximately 3.0 million incident AD cases. PM2.5 exposure (5-year moving average prior to AD onset) was associated with increased risk of AD in the overall population (hazard ratio [HR]) per interquartile range [IQR, 3.8 µg/m3] increase: 1.085 (95% CI: 1.078, 1.091]. This association was slightly stronger in individuals with stroke (HR per IQR increase: 1.105; 95% CI: 1.096, 1.114), but there was little effect modification for hypertension and depression. PM2.5 exposure was also significantly associated with higher risks of hypertension, depression, and stroke, all of which were also linked to increased AD risk. However, mediation effects were minimal, with 1.6% of the association between PM2.5 and incident AD mediated by hypertension, 4.2% by stroke, and 2.1% by depression. Study limitations include use of administrative claims data and potential exposure misclassification from area-level PM2.5 estimates. CONCLUSIONS: Our findings suggest that PM2.5 exposure was associated with increased AD risk, primarily through direct rather than comorbidity-mediated pathways. Stroke may modestly increase susceptibility. These findings highlight the need for air quality interventions as part of dementia prevention strategies in aging populations, especially those facing overlapping environmental and clinical vulnerabilities.
Eliminating ghost workers and optimizing resources to strengthen Community Health Worker programs in sub-Saharan Africa.
Ayehu T, Joekai JF, Yorgbor MK … +19 more , Clark ET, Jacobs GP, Brooks-Jarrett CE, Wiah SO, Fatoumata S, Dialo M, Frederic LD, Kamara BO, Williams CEE, Kamara MST, Beckhio M, Marcelin AA, Mbrenga NC, Edouard B, Theirry S, Emery H, Dushime T, Barry H, Getahun H
PLoS Med · 2026 Feb · PMID 41701657 · Full text
Although community health workers (CHWs) play a vital role in filling health workforce gaps, they remain inadequately compensated due to insufficient domestic financing. In this Policy Forum article, Temesgen Ayehu and c...
Although community health workers (CHWs) play a vital role in filling health workforce gaps, they remain inadequately compensated due to insufficient domestic financing. In this Policy Forum article, Temesgen Ayehu and colleagues discuss how elimination of ghost workers and healthcare reform in Sub-Saharan Africa can release funds to properly pay and integrate CHWs into civil service programs.
Estimating the population impact of new tuberculosis vaccines depending on efficacy against infectious asymptomatic tuberculosis: A modelling study.
Tanvir H, Clark RA, Sumner T … +9 more , Horton KC, Prŷs-Jones TO, Bakker R, Rade K, Mave V, Hatherill M, Churchyard GJ, Houben RMGJ, White RG
PLoS Med · 2026 Feb · PMID 41678562 · Full text
BACKGROUND: Tuberculosis (TB) remains a leading cause of infectious disease death. New TB vaccines are currently in late-stage trials and may be available before the end of the decade. Modelling predicts new TB vaccines...
BACKGROUND: Tuberculosis (TB) remains a leading cause of infectious disease death. New TB vaccines are currently in late-stage trials and may be available before the end of the decade. Modelling predicts new TB vaccines may reduce global burden but rely on assumptions about vaccine efficacy by TB disease stage and TB natural history, which may be incorrect. We explored the sensitivity of estimates of the impact of new TB vaccines to uncertainties in efficacy by disease stage and natural history. METHODS AND FINDINGS: We developed a dynamic compartmental TB model for India, including early TB disease stages (non-infectious disease, infectious asymptomatic disease, and infectious symptomatic disease). Scenarios assumed 50% vaccine efficacy for 10 years and prevented progression to (a) only infectious symptomatic disease, or (b) any infectious disease (infectious asymptomatic disease and infectious symptomatic disease), or (c) any disease (non-infectious disease, infectious asymptomatic disease, and infectious symptomatic disease). We estimated impact on averting disease episodes over 2030-2050, compared to no-new-vaccine introduction. Results suggest, over 3 years, there was little difference in the proportion of cumulative symptomatic disease episodes averted by vaccines preventing only infectious symptomatic disease, any infectious disease, or any disease (1.6%, 2.3%, and 2.3%, respectively). However, over 20 years, compared to vaccines preventing only infectious symptomatic disease, vaccines preventing any infectious disease, or any disease, averted a markedly higher proportion of symptomatic disease episodes (7.3%, 19.4%, and 23.3%, respectively), due to preventing continued transmission from infectious asymptomatic disease. A key limitation with any mathematical modelling study is the uncertainty associated with the inputs, and further data collection is required to better understand the transmissibility, morbidity, and dynamics of asymptomatic disease, to improve modelling estimates and inform wider policy. CONCLUSIONS: Our modelling estimates that the population impact of new TB vaccines may depend on efficacy against infectious asymptomatic disease. TB vaccine trials should include analyses of participant sputum samples (collected during or at the end of trials and analysed at the end of trials) to enable better estimates of the potential value of new TB vaccines against infectious asymptomatic disease.
Evaluation of rotavirus, pneumococcal conjugate and human papillomavirus vaccination in four Pacific island countries: A cost-effectiveness modelling study.
Carvalho N, Watts E, Oliver VL … +12 more , Clark A, Ozturk MH, Akauola S, Whelan C, Naseri T, Jenkins K, Mikkelsen-Lopez I, Lam KFK, Rabanal R, McLeod R, Jit M, Russell FM
PLoS Med · 2026 Feb · PMID 41678506 · Full text
BACKGROUND: The introduction of rotavirus vaccine (RVV), pneumococcal conjugate vaccine (PCV) and human papillomavirus vaccine (HPVV) has been slow in Pacific Island Countries, particularly among middle-income countries....
BACKGROUND: The introduction of rotavirus vaccine (RVV), pneumococcal conjugate vaccine (PCV) and human papillomavirus vaccine (HPVV) has been slow in Pacific Island Countries, particularly among middle-income countries. To assist decision-making on the simultaneous introduction of these three vaccines, cost-effectiveness and budget impact evaluations were undertaken in Samoa, Tonga, Tuvalu and Vanuatu, using locally relevant data. METHODS AND FINDINGS: A proportionate outcomes model was used to evaluate vaccine introduction in each country from a health systems perspective, using country-specific data supplemented with regional and global estimates. A 10-year vaccination program was modelled from 2021, with costs and outcomes (disability-adjusted life years [DALYs]) summed over a life-time horizon and discounted at 3%. Vaccine dose costs were based on Pan American Health Organization (PAHO) Revolving Fund prices, with lower-priced products also explored. Introduction of all three vaccines in all countries could prevent over 1,000 deaths over the lifetimes of the vaccinated cohorts. The cost per DALY averted at PAHO Revolving Fund prices ranged from 42% to 73% of the per capita gross domestic product (GDP) in each country, and 15% to 58% for lower-priced vaccines. The budget impact ranged from 359% (Samoa) to 1,368% (Vanuatu) of the 2019 vaccine budgets, and 149% (Samoa) to 775% (Vanuatu) for lower-priced vaccines. Cost-effectiveness results were most sensitive to disease burden, discount rate, vaccine efficacy, and program costs. A limitation of our study is the reliance on data from Fiji to inform disease burden, as availability of country-specific data was limited. CONCLUSIONS: With development partner support, introduction of HPVV, PCV and RVV may represent good value for money in Samoa, Tonga, Tuvalu and Vanuatu, depending on willingness to pay thresholds. However, inclusion of these three vaccines will place considerable burden on immunisation budgets. Financial sustainability requires increases in immunisation budgets and negotiation of affordable vaccine prices. This analysis provides evidence of the benefit of introducing new vaccines, but shows the importance of affordable pricing to ensure sustainability for small Pacific Island countries.
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