PLoS Medicine最新文献

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.

Background: With the healthcare sector contributing nearly 5% of total global greenhouse gas (GHG) emissions globally, a precise assessment of their carbon footprint is crucial for achieving carbon neutrality targets. This study aims to comprehensively assess the carbon footprint of Chinese healthcare service providers, to identify their driving activities and sources across different time periods, and to provide a solid foundation for the development of effective emission reduction policies in healthcare service in China.

Methods and findings: The data on overall national health expenditures for 2012 and 2018, as well as expenditures by different levels of hospitals, various hospital departments, and specific diseases, were sourced from China's Health Statistics Yearbooks and national input-output tables (IOTs). Environmentally extended input-output analysis (EEIOA) and structural path analysis (SPA) were utilized to assess the carbon footprint of healthcare services in China in 2012 and 2018. Overall, the total carbon footprint of Chinese healthcare service providers increased by 51 MtCO2e (15%) in 2018 compared to that in 2012, accounting for about 3.7% of the total domestic GHG emissions. In 2018, public hospitals made the largest contribution to the carbon footprint within the national health expenditure categories, with their carbon emissions increasing by 29 MtCO2e (19%). Among medical institutions, procurement was the largest contributor to the carbon footprint, with emissions increasing by 46 MtCO2e (25%). Within hospital departments, the internal medicine department had the highest carbon footprint, reaching 47.66 MtCO2e (26%) in 2018. When classified by hospital grades, tertiary hospitals contributed the most, emitting 126.50 MtCO2e (70%). When classified by disease category, circulatory system diseases had the largest carbon footprint of 12.68 MtCO2e (19%), while malignant neoplasms were the primary contributor among subcategory diseases, emitting 5.52 MtCO2e (8%). The main limitation of this study lies in the fact that national IOTs are updated approximately every 5 years, and data for methane (CH₄) and nitrous oxide (N₂O) have not been updated since 2018. As a result, the analysis could only be performed for the years 2012 and 2018.

Conclusions: These findings highlighted the substantial GHG emission contributions in China from public hospitals, especially tertiary hospitals, procurement activities, Internal Medicine Departments, and specific diseases in the carbon footprint. The findings provided robust scientific evidence for formulating strategies to reduce carbon emissions within the healthcare service in China and will also have implications for other countries.

Background: It is unknown whether fasting plasma glucose (FPG) level within the normal range as defined by the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria is associated with perinatal outcomes. This study explored the associations between FPG levels lower than the IADPSG threshold during oral glucose tolerance test (OGTT) and adverse perinatal outcomes in women with or without gestational diabetes mellitus (GDM).

Methods and findings: From January 1, 2017, to May 31, 2022, this single-center retrospective cohort study included 33,417 women with singleton pregnancies at the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. All women underwent a 75-g OGTT at 24-28 gestational weeks. The primary endpoint was a composite of adverse outcomes, including gestational hypertension, preeclampsia, fetal death and stillbirth, preterm birth, primary cesarean delivery, and small or large for gestational age. Overall, 3,108 (9.5%) women had IADPSG-defined GDM and of whom 2,426 (76.3%) had FPG levels below the IADPSG threshold. Compared to the GDM population, non-GDM women with borderline-normal FPG levels were at significantly greater risk of adverse outcomes with an adjusted odds ratio (aOR) of 1.62 (95% CI [1.20, 2.19]; p = 0.002) at 4.6 mmol/L, an aOR of 1.50 (95% CI [1.05, 2.13]; p = 0.025) at 4.8 mmol/L, and an aOR of 1.58 (95% CI [1.05, 2.40]; p = 0.030) at 4.9 mmol/L glucose level. Nonetheless, non-GDM women demonstrated significantly lower risk (aOR 0.66, 95% CI [0.44, 0.98]; p = 0.038) compared to GDM counterparts exhibiting low fasting glycemia at 3.9 mmol/L. However, this study was limited by its retrospective design and may lack generalizability to other ethnic groups.

Conclusions: Even at FPG levels lower than the IADPSG threshold, FPG was significantly associated with adverse perinatal outcomes, and the associations presented different patterns in women with and without GDM.

[This corrects the article DOI: 10.1371/journal.pmed.1004541.].

Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is a chemoprevention strategy against malaria in pregnancy. A recent PLOS Medicine study highlights the need for better understanding of the mechanism by which IPTp-SP reduces low birthweight, as well as novel measures to prevent malaria earlier in gestation.

Background: Depression and burnout, which are common among healthcare workers, were exacerbated by the COVID-19 pandemic. Mindfulness-Based Stress Reduction (MBSR) and psilocybin have been reported to reduce depressive symptoms, but the efficacy of the combination requires comparison to an active treatment control. We sought to evaluate the safety and preliminary efficacy of psilocybin and MBSR versus MBSR alone for frontline healthcare providers with symptoms of depression and burnout related to the COVID-19 pandemic. We hypothesized that psilocybin would augment the antidepressant effects of MBSR in this population.

Methods and findings: We conducted a randomized controlled trial that enrolled physicians and nurses with frontline clinical work during the COVID-19 pandemic and symptoms of depression and burnout. (ClinicalTrials.gov Identifier: NCT05557643) Participants were enrolled between January 2nd, 2023 and January 16th, 2024, and randomized in a 1:1 ratio to either an 8-week MBSR curriculum alone or an 8-week MBSR curriculum plus group psilocybin-assisted psychotherapy (PAP) with 25 mg psilocybin. Evaluation of safety and feasibility of enrollment and retention was a primary objective of the study. The primary efficacy endpoint was change in depressive symptoms, as measured by the Quick Inventory of Depressive Symptoms (QIDS-SR-16) at 2 weeks post-intervention. Symptoms of depression and burnout were assessed at baseline, and 2 weeks and 6 months post-intervention utilizing the Quick Inventory of Depressive Symptoms (QIDS-SR-16) and Maslach Burnout Inventory Human Services Survey for Medical Professionals (MBI-HSS-MP), respectively. Secondary outcome measures included the Demoralization Scale (DS-II) and the Watt's Connectedness Scale (WCS). Adverse events (AEs) and suicidality were assessed through a 6-month follow-up. Twenty-five participants were enrolled and randomized. Safety was a study outcome and assessed by rate and severity of AEs and any incident suicidality or significant mental health symptoms. Baseline and outcome data were summarized using descriptive statistics, with continuous variables reported as means and standard deviations. We recorded 12 study-related, Grade 1-2 AEs and no serious AEs. In a linear mixed model analysis (LMM), the MBSR + PAP arm evidenced a significantly larger decrease in QIDS-SR-16 score than the MBSR-only arm from baseline to 2-weeks post-intervention (between-groups effect = 4.6, 95% CI [1.51, 7.70]; p = 0.008). This effect waned at the 6-month follow-up. Secondary outcome measures for burnout (subscales of the MBI-HSS-MP), demoralization (DS II), and connectedness (WCS) favored the MBSR + PAP arm; however, these effects did not survive correction for multiple comparisons. A mixed RM-ANCOVA was conducted to control for baseline differences in outcome measures. Sensitivity analyses were conducted, adjusting for baseline differences in gender and clustering