PLoS Medicine最新文献

Background: DS-5670d is a monovalent lipid nanoparticle-messenger ribonucleic acid vaccine against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), containing an omicron XBB.1.5-derived antigen. This phase 3 non-inferiority study assessed the immunogenicity and safety of a single dose of DS-5670d according to participant immune status.

Methods and findings: Participants aged ≥12 years were stratified according to their history of both prior SARS-CoV-2 infection plus prior coronavirus disease 2019 vaccination (subpopulation A), prior infection only (subpopulation B), prior vaccination only (subpopulation C), or no history of either infection or vaccination (subpopulation D), and randomly assigned (1:1) to receive DS-5670d or monovalent BNT162b2 omicron XBB.1.5. The primary efficacy endpoint was geometric mean titer (GMT) of blood neutralizing activity against SARS-CoV-2 (omicron XBB.1.5) and seroresponse rate at day 29 after study vaccine administration in the combined ABC subpopulations (DS-5670d, n = 362 versus BNT162b2, n = 363). Prespecified non-inferiority margins required that the lower limit of the 95% confidence interval (CI) exceeded 0.67 for the GMT ratio and -10% for the difference in seroresponse. The adjusted GMT ratio was 1.218 (95% confidence interval [CI], 1.059, 1.401). Seroresponse rates were 87.3% (DS-5670d) and 82.9% (BNT162b2); adjusted difference 4.5% (95% CI, -0.70, 9.71). Both results exceeded the non-inferiority margins and the study met the primary endpoint. Immunogenicity data in the overall ABCD population also met non-inferiority criteria. There were no apparent immunogenicity differences according to age or sex, and analyses suggested that even unvaccinated persons achieved an adequate immune response following a single dose of DS-5670d. There were no major differences in the incidence or severity of adverse events between the study vaccination groups. The main study limitation was the short duration of follow-up.

Conclusions: A single dose of DS-5670d was immunogenically non-inferior to BNT162b2 and acceptably safe in persons with or without a history of prior infection and/or vaccination. Trial registration Japan Registry of Clinical Trials (jRCT2031230424).

A recent PLOS Medicine study reveals the wide variation in psychiatric bed numbers across the US. Globally, capacity differs 80-fold among OECD countries, reflecting history, policy, and care models. Without global standards and access, the efficiency and quality of psychiatric care remain uneven.

Background: Post-acute sequelae (PAS) of SARS-CoV-2 infection are well documented. However, it remains unclear whether such long-term health effects are unique to COVID-19, or also occur following other viral respiratory infections.

Methods and findings: We undertook a retrospective cohort study of 74,738 COVID-19 cases and 18,790 influenza cases within the Kaiser Permanente Southern California healthcare system diagnosed between 1 September, 2022 and 31 December, 2023. Cases received care for index infections across a spectrum of clinical settings, spanning virtual (n = 35,835; 38.3%), ambulatory (n = 26,579; 28.4%), emergency department (n = 23,388; 25.0%) and inpatient (n = 7,726; 8.3%) facilities. We compared 180-day risk of PAS-related healthcare utilization among COVID-19 cases and influenza via adjusted hazard ratios (aHRs) weighted to account for cases' index infection type and follow-up retention. Adjustment models addressed patients' demographic characteristics, comorbidity profiles, prior healthcare utilization patterns, and index episode severity. Risk of PAS diagnoses in any clinical setting was only modestly higher among COVID-19 cases in comparison to influenza cases within 31-90 days after cases' initial illness (aHR = 1.04 [95% confidence interval: 0.99, 1.09]; risk difference = 0.6 [-0.1, 1.2] cases per 100 person-months). This difference was attenuated by 91-180 days (aHR = 1.01 [0.97, 1.06]; risk difference = 0.4 [-0.1, 0.9] cases per 100 person-months). However, COVID-19 cases faced higher risk of severe PAS conditions requiring hospitalization (aHR = 1.31 [1.07, 1.59] and 1.24 [1.03, 1.49] within 31-90 and 91-180 days, respectively). This excess risk of severe PAS was concentrated among COVID-19 cases hospitalized during acute-phase illness, and was attenuated among cases who received antiviral treatment, who had up-to-date vaccination status prior to infection, or who did not require inpatient admission for acute-phase illness. As a limitation, analyses included only PAS resulting in healthcare utilization; patient-reported symptoms and quality-of-life measures were not captured.

Conclusions: In this large, real-world cohort, individuals with non-severe acute respiratory illness caused by SARS-CoV-2 experienced only modestly greater risk of PAS in comparison to those whose illness was caused by influenza. However, COVID-19 cases hospitalized for their initial illness experienced greater risk of severe PAS necessitating inpatient care, and this difference persisted through 180 days of follow-up. Our findings challenge assumptions about the uniqueness of post-acute COVID-19 morbidity and suggest the long-term burden of influenza may be underrecognized.

Background: Annually, an estimated 2.3 million infants die within their first month of life, primarily in sub-Saharan Africa and South Asia. Infections, including sepsis are among the major contributors to these deaths. Effective interventions added to standard antimicrobial therapy can reduce sepsis mortality. A recent meta-analysis suggests that adjunct zinc treatment of young infants with sepsis could reduce case fatality risk. This study evaluated the efficacy of zinc as an adjunct to antibiotics in young infants with suspected sepsis, defined as clinical severe infection (CSI).

Methods and findings: We conducted a randomized, double-blind, placebo-controlled trial across seven hospitals in India and Nepal from February 28, 2017, to February 22, 2022. Infants aged 3-59 days hospitalized with suspected sepsis, defined as CSI, adapted from the WHO Integrated Management of Childhood Illness (IMCI) criteria, were randomly assigned to receive 10 mg of elemental zinc daily or placebo orally for 14 days, in addition to standard of care. The primary outcomes were death during hospitalization and death within 12 weeks after enrollment. Among 3,153 enrolled infants (1,203 [38%] females), the median age at enrollment was 25 days (interquartile range 13-41 days), and the mean weight was 2.9 kg (standard deviation 0.8). During the hospital stay, 64 (4.1%) of 1,576 infants died in the zinc arm compared to 77 (4.9%) of 1,577 in the placebo arm (relative risk [RR] 0.83 (95% CI [0.60, 1.15]; p = 0.267)). Among those who completed 12 weeks of follow-up, 140 of 1,554 infants (9.0%) died in the zinc arm, and 133 of 1,550 (8.6%) in the placebo arm (RR 1.05 (95% CI [0.84, 1.32]; p = 0.674)). Adverse events were similar across trial arms, except for a slight increase in vomiting in the zinc arm; no events were attributed to the intervention. The main limitation of the study is that it was underpowered due to lower-than-anticipated event rates and a shortfall in the achieved sample size.

Conclusions: In this setting, we found little evidence for an effect of adjunct zinc therapy on young infants with CSI on the risk of dying during hospitalization or for the subsequent 3 months. Our findings contrast previous studies that used more specific case definitions. This underscores the need for further RCTs to evaluate the effect of zinc in young infant sepsis before it can be recommended in treatment guidelines.

Trial registration: Clinical Trials Registry-India (CTRI/2017/02/007966) on February 27, 2017, and Universal Trial Number is U1111-1187-6479.

New evidence suggests that mass drug administration of azithromycin (MDAA) can significantly reduce childhood mortality in high-burden, low-resource settings, yet the World Health Organization's (WHO) 2020 guidelines take a cautious approach due to concerns about antimicrobial resistance (AMR).While the WHO guidelines cite ethical principles, they insufficiently address key considerations, such as intergenerational justice, equitable burden sharing, and the structural determinants of health that shape infectious disease vulnerability.Global AMR policy often prioritizes conservation over access in ways that disproportionately burden low-income countries, despite high-income countries also bearing significant responsibility for the emergence and spread of AMR.A balanced ethical framework is needed: one that explicitly integrates contextual values, including justice across generations, historical inequities, and community input under uncertainty.Revised WHO guidelines that expand eligibility for MDAA based on context-specific criteria, establish thresholds for mortality and resistance monitoring, and encourage global investment in sustainable health systems and antibiotic access, may better align with the WHO's own principles on equity, human rights, and social determinants of health in the development of guidelines.

Background: While apixaban has demonstrated advantages over alternative direct oral anticoagulants (DOACs) in some settings, its comparative safety and effectiveness in cancer-associated venous thromboembolism (VTE) remain uncertain. Current guidelines recommend DOACs as first-line treatment for cancer-associated VTE, though they do not recommend any specific DOAC over another. This study aimed to quantify the risk of recurrent VTE, major bleeding, and clinically relevant non-major bleeding among individuals with cancer-associated VTE treated with apixaban versus rivaroxaban.

Methods and findings: In this retrospective cohort study, we used data from Medicare fee-for-service (2016-2020) and MarketScan (2016-2022), two U.S. administrative claims databases covering publicly and commercially insured individuals. We included individuals aged ≥65 years (Medicare) or 18-64 years (MarketScan) with active cancer, defined as a cancer diagnosis within 6 months before an index VTE event, who newly initiated apixaban or rivaroxaban within 30 days of that event. The outcomes were (1) hospitalization for recurrent VTE; (2) hospitalization for major bleeding; and (3) hospitalization or outpatient visit for clinically relevant non-major bleeding events. Eligible individuals were followed for outcomes at 6 months (consistent with guideline recommendations) and during the entire follow-up period. We used inverse probability of treatment weighting to adjust for baseline differences, including demographics, comorbidities (e.g., prior bleed), VTE risk factors, cancer type and treatments, and medication use, and applied inverse probability of censoring weighting to account for differential loss to follow-up. We analyzed outcomes using adjusted Cox proportional hazards models, pooling estimates using an inverse variance-weighted fixed-effects model. The final cohort included 6,329 apixaban and 4,260 rivaroxaban users across both databases. At 6 months, apixaban was associated with similar risks of recurrent VTE (hazard ratio [HR] 0.66, 95% confidence interval [CI] [0.40, 1.11]; p-value = 0.11) and major bleeding (HR 0.95, 95% CI [0.73, 1.23]; p = 0.70), and a lower risk of clinically relevant non-major bleeding (HR 0.84, 95% CI [0.74, 0.96]; p = 0.009) compared to rivaroxaban. The same pattern persisted during the extended follow‑up. The main limitation is the observational design, which may leave residual confounding despite adjustments using inverse probability weighting.

Conclusions: In cancer-associated VTE, apixaban was associated with similar risks of recurrent VTE and major bleeding, and a lower risk of clinically relevant non-major bleeding compared with rivaroxaban. These findings suggest apixaban may be a favorable option for anticoagulation in cancer-associated VTE when minimizing bleeding risk is a priority.

Background: Self-harm is a major public health concern globally and in South Africa. Individuals with a history of self-harm are at increased risk of unnatural death, including suicide and fatal accidents. This study investigates the incidence and predictors of self-harm and its role as a predictor for subsequent unnatural death.

Methods and findings: We conducted a cohort study using insurance claims and vital registration data from beneficiaries of South African medical insurance schemes (2011-2022), aged 10 years or older. We estimated the cause-specific cumulative incidences of healthcare encounters for intentional self-harm (International Classification of Diseases 10th Revision [ICD-10] codes X60-X84) and unnatural deaths (ICD-10 codes V01-Y98), using the Aalen-Johansen method. We assessed predictors of both outcomes using Cox regression. We followed 1,356,119 beneficiaries (median age 33 years, 52.2% female) for a median of 3 years, during which 7,510 (0.6%) had a healthcare encounter for self-harm. The 5-year cumulative incidence of self-harm ranged from 0.2% in males aged 10-14 to 2.1% in females aged 15-24. Sex, age, and mental disorders were strong predictors for self-harm, while HIV was a modest predictor. Among individuals who survived a self-harm event, the five-year cumulative incidence of subsequent unnatural death was 3.43% (95% CI [2.38, 4.76]) for males and 0.77% (95% CI [0.48, 1.19]) for females. Non-fatal self-harm was a strong predictor of subsequent unnatural death in both males (hazard ratio [HR] 7.03, 95% CI [5.27, 9.39]) and females (HR 4.63, 95% CI [3.00, 7.15]). The study's main limitations include potential under-ascertainment of self-harm incidence due to reliance on routine data, and the unavailability of the exact cause of death, preventing analysis of suicide.

Conclusion: Self-harm is common among beneficiaries of South African private medical insurance, with the highest risk in young females and individuals with mental disorders. These groups may benefit from targeted screening and early intervention. Non-fatal self-harm was a strong predictor of subsequent unnatural death, underscoring the need for suicide-specific brief interventions for individuals presenting with self-harm.

Systematic fraud threatens the integrity of science, with paper and review mills distorting the evidence base in medicine and global health. Data transparency-once seen mainly as a driver of discovery-must now be recognized as a frontline defense against misconduct. Only through open data and coordinated action can we safeguard trust in research and its impact on health.

Background: Climate change has exacerbated the frequency, intensity, and impacts of extreme weather events (EWEs), such as tropical cyclones. However, the increasing impact of tropical cyclones on child mortality, especially in low- and middle-income countries (LMICs), remains understudied.

Methods and findings: Utilizing individual-level data from the Demographic and Health Surveys, we conducted a sibling-matched case-control study to assess the impact of cyclone exposure over the past 3 months on under-five mortality. The study included 100,798 under-five deaths and 247,445 controls across 34 LMICs from 1993 to 2021. After adjusting for key meteorological and temporal confounders and maternal age, significant positive associations were observed between under-five deaths and cyclone exposure over the past 3 months before death (odds ratio [OR]: 1.038, 95% confidence interval [CI]: 1.002, 1.075; p = 0.041). Specifically, the strongest effects were observed in the first month before death (OR: 1.101, 95% CI: 1.039, 1.166; p < 0.001), diminishing in the second and third months before death. We estimated that cyclone exposure 0-30 days before death may have caused 0.85 million under-five deaths (95% CI: 0.35 million, 1.32 million) in countries exposed to cyclones from 2000 to 2020. As an observational study, its use of self-reported data and dichotomous exposure assessment may introduce recall bias and exposure misclassification, limiting accuracy and representativeness.

Conclusions: This global analysis demonstrates the substantial under-five mortality risk from cyclones, emphasizing the importance of targeted strategies to enhance community resilience against the growing threat of EWEs on children, such as improving access to water sources and sanitation facilities.