PLoS Medicine最新文献

Large open health datasets present unique opportunities for studies that when well-designed, conducted, and reported, can offer valuable contributions to health and medicine. However, recent years have seen a concerning proliferation of analyses lacking robust or novel findings. In this Editorial, we provide guidance to authors for conducting and reporting high-quality secondary analyses using these datasets.

Background: Onco-hypertension recognizes well-controlled blood pressure as a favorable prognostic factor for survival in patients with hypertension and solid tumors, including hematologic neoplasms. However, it remains unknown whether continuous use of hydralazine-an antihypertensive agent (AHA) with notable anti-neoplastic activity-is associated with a lower risk of hematologic neoplasms compared to other AHAs.

Method and findings: Utilizing Taiwan's National Health Insurance Research Database, we conducted a 16-year follow-up study (2000-2015) involving 375,107 patients with hypertension treated with an AHA for ≥180 days. The patients with hypertension were divided into two groups based on hydralazine prescription duration: an exposure group (hydralazine ≥180 days; n = 59,786) and a reference group (hydralazine <180 days; n = 239,144) after 1:4 matching for sex, age, and index date with the exposure group. Both groups were well-matched, with a mean age of approximately 60.8 years and 52.19% male. We assess the association between hydralazine use and the risk of hematologic neoplasms using Kaplan-Meier analysis and multivariable Cox proportional hazards regression, with models adjusted for concomitant medications possessing potential anti-neoplastic properties. The 16-year cumulative incidence of hematologic neoplasms was lower in the exposure group (105.58 per 100,000 person-years) than in the reference group (160.33). Accounting for death as competing risk, the exposure group exhibited an adjusted subdistribution hazard ratio (adjusted sHR) of 0.789 (95% confidence interval [0.667,0.913]; P < .001) for hematologic neoplasms compared to the reference group. Subgroup analyses demonstrated that the association with a lower risk was strongest in the longest prescription duration category. For example, for patients with prescription durations of ≥668 days, the adjusted sHR was 0.448 (95% CI [0.366,0.555]; P < .001) for other malignant neoplasms of lymphoid and histiocytic tissue, 0.552 (95% CI [0.453,0.683]; P < .001) for multiple myeloma and immunoproliferative neoplasms, and 0.555 (95% CI [0.457,0.689]; P < .001) for myeloid leukemia. The main limitation was the potential for residual confounding due to the unavailability of lifestyle and laboratory data in the administrative database.

Conclusions: In this study, we observed that long-term hydralazine use in patients with hypertension was associated with a lower, duration-dependent risk of hematologic neoplasms. These findings warrant prospective studies to confirm this association and its potential clinical implications.

Background: Globally, maternal mortality is off track in achieving the Sustainable Development Goals by 2030. Over the past two decades, China has dramatically reduced maternal mortality in more developed (eastern) and less developed (western) regions. An understanding of the social and health system factors associated with maternal mortality in China may be helpful for countries attempting to meet the 2030 targets and beyond.

Methods and findings: We analyzed provincial-level data on maternal mortality and social and health system factors from the National Health Statistics Yearbooks and China Statistical Yearbooks from 2004 to 2020. We investigated the factors associated with maternal mortality before and after 2013, the year that a historic national program, Reducing Maternal Mortality and Eliminating Neonatal Tetanus, came to an end. Bayesian kernel machine regression was employed to analyze social and health system factors (urbanization rate, per capita disposable income, average years of schooling, number of health technical personnel in maternal and child healthcare, number of hospital beds for obstetrics and gynecology, local fiscal expenditure on healthcare, prenatal booking rate, antenatal care rate, and hospital delivery rate) as a mixture and identify the factors with larger posterior inclusion probability and a higher value of the exposure-response relationship for the total and cause-specific maternal mortality. In the East, an increase in hospital delivery rate correlated with the decrease in total maternal mortality [posterior mean and standard deviation (SD): -14.8(1.5)] before 2013, and the urbanization rate was negatively associated with total maternal mortality [posterior mean and SD: -3.9(0.6)] after 2013. Hospital delivery, urbanization, local fiscal expenditure on healthcare, and antenatal care were the factors associated with reduced cause-specific maternal mortality in the East. In the West, an increase in antenatal care rate was associated with reduced total maternal mortality, with the posterior mean and SD of -33.8(6.8) and -11.5(4.1) before and after 2013, respectively. Hospital delivery and antenatal care were the factors associated with reduced cause-specific maternal mortality in the West. The main limitation of this study was the data constraints in the national statistics.

Conclusions: Coverage of maternal care, health financing, and urbanization were the factors associated with the substantial reduction in maternal deaths in Eastern and Western China during 2004-2020. The improvement of the quantity and quality of antenatal care and hospital delivery may be a viable policy priority in less developed regions worldwide.

Background: Hallucinogen use for both recreational and medical purposes is rapidly increasing globally, raising concerns about potential adverse effects. This study examined the risk of incident mania or bipolar disorder (BD) diagnosis associated with having an emergency department (ED) visit or hospitalization involving hallucinogens.

Methods and findings: We used a population-based cohort study of all individuals aged 14-65 years with no baseline history of BD and registered in the Ontario Health Insurance Plan in Ontario, Canada, between 2008-2022. Incident mania (primary outcome) and incident BD (secondary outcome) were compared between individuals with acute care (an ED visit or hospitalization) involving hallucinogens and the general population using overlap propensity score weighted Cox proportional hazard models. Models were adjusted for age, sex, rural residence, income quintile, recent documentation of homelessness, and healthcare encounters for mental health or other substance use in the past five years. The study included 9,311,844 individuals of which 7,285 (0.08%) had acute care involving hallucinogens. Within 3-years of acute care involving hallucinogens, 1.43% (n = 104) of individuals had an incident episode of mania requiring acute care compared to 0.06% (n = 41) of individuals in the age-sex matched general population, a 25-fold increase in risk. After weighting, acute care for hallucinogens was associated with a 6-fold (weighted Hazard Ratio [HR] 5.97, 95% CI 3.29, 10.82) increase in risk of incident mania relative to individuals without hallucinogen acute care who had otherwise similar demographic and mental health histories. Associated increases were also observed for risk of an incident diagnosis of BD (HR 3.75 95%CI 2.49, 5.65, absolute proportion 2.50% versus 0.11%). The main limitation of the study is the risk associated with the exposure examined in this study may not generalize to the majority of people who use hallucinogens who do not require acute care.

Conclusions: These findings suggest the need for ongoing caution regarding hallucinogen use in individuals at risk of bipolar disorder. They also have potential implications for clinical practice, research, and public health policy, including substance regulation and targeted education for high-risk groups in the context of rising hallucinogen use.

Since the inception of World AIDS Day in 1988, advances with antiretroviral drugs have revolutionized the landscape of HIV/AIDS treatment and prevention. In 2025, we reflect on progress made, highlight promising therapeutic developments, and look ahead to what is needed to end the AIDS epidemic.

The Global Burden of Disease 2023 represents the most comprehensive iteration of its kind since first reported in 1993. Despite improved health monitoring, data acquisition, and analytical methods, its expansion creates new challenges and opportunities for improving its accuracy, completeness, external validity, and policy relevance.

Background: Implant revision is an operation with exchange of implants, and is used as a standard outcome after total hip replacement (THR), but may not fully represent the patient experience after a THR. Major reoperation (hereafter referred to as 'reoperation') without revision of implants can also lead to increased patient morbidity and mortality, and most commonly occurs when the femur fractures around an implant (postoperative periprosthetic femoral fractures; POPFF) and is treated with fixation and the implant is left in place. Reliance on revision metrics that do not capture these reoperations has led to large-scale underreporting of reoperations in THR, and is likely to have affected implant performance estimates, which have guided national policy and implant selection. It is important to include these additional reoperations when estimating treatment success to guide innovation and clinical practice. We aimed to estimate the incidence of reoperation following primary THR.

Methods and findings: We performed a large national cohort study on a mandatory, prospective database, the National Joint Registry, linked to Hospital Episode Statistics. All linkable primary THRs using recently available implants, with highest safety ratings between 01/01/2010 and 31/12/2020, were included. Major reoperation was defined as the first revision for any cause or fixation of POPFF and was identified using a combination of procedural and diagnosis codes. We identified 372,967 THRs representing 2,127,464 prostheses years at risk with a median follow-up time of 5.39 years (range 0 to 12.1 years). A total of 8,043 reoperations were identified that had been surgically treated by revision for any cause or fixation of POPFF. The incidence of reoperation was 3.78% (95% confidence interval [CI 3.70%, 3.86%]) per 1,000 prostheses years in comparison to 3.00% (95% CI [2.93%, 3.07%]) per 1,000 prostheses years when using conventional revision only outcomes. Cumulative incidence of major reoperation at 10 years was 3.1% (95% CI [3.0%, 3.1%]). Cumulative reoperation estimates were stratified by age and sex. In men aged 68 years and older, collared cementless stems performed better than cemented stems and in women aged 75 years and older, the relationship was reversed. Residual differences in patient characteristics may affect the accuracy of the estimates.

Conclusions: Treatment failure after THR has been underrepresented by revision-only estimates. Major reoperation rates in older men were lowest with cementless collared stems, and in older women, reoperation rates were lowest with cemented polished taper stems made of stainless steel. These results prompt a review of the current implant guidance for hip replacements in older patients.

Level of evidence: III (Retrospective cohort study).

The discovery of insulin transformed type 1 diabetes from an acutely lethal illness to a chronic disease that is managed with insulin dependence. Now, exciting developments in preventive treatments and stem cell-based therapies bring the prospects of arresting the disease and achieving insulin independence for type 1 diabetics closer to reality.