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Impact of combined hormonal contraceptives and metformin on metabolic syndrome in women with hyperandrogenic polycystic ovary syndrome and obesity: The COMET-PCOS randomized clinical trial. 联合激素避孕药和二甲双胍对高雄激素性多囊卵巢综合征和肥胖女性代谢综合征的影响:COMET-PCOS随机临床试验
IF 9.9 1区 医学 Q1 Medicine Pub Date : 2025-12-08 eCollection Date: 2025-12-01 DOI: 10.1371/journal.pmed.1004662
Anuja Dokras, Christos Coutifaris, Alan T Remaley, Nehal N Mehta, Martin P Playford, Allen R Kunselman, Christy C Stetter, William C Dodson, Richard S Legro
<p><strong>Background: </strong>The risk-to-benefit ratio of using combined oral contraceptive pills (COCPs) and/or metformin for comprehensive management of polycystic ovary syndrome (PCOS) in women with obesity is unclear. As there is a lack of robust evidence on the impact of these first-line medications on cardiovascular disease (CVD) risk, we compared the effect of COCPs, metformin or both on prevalence of metabolic syndrome (MetS) in participants with hyperandrogenic PCOS and hypothesized that COCPs would increase prevalence of MetS while metformin would decrease prevalence of MetS.</p><p><strong>Methods and findings: </strong>We conducted a multicenter, double-blind, double-dummy, randomized trial (COMET-PCOS) in participants between ages ≥18 and ≤40 years and body mass index (BMI) ≥25 kg/m2 and ≤ 48 kg/m2 with hyperandrogenic PCOS (defined by the Rotterdam criteria). Participants were randomized 1:1:1 to 24 weeks of low-dose COCPs (20 μg ethinyl estradiol/0.15 mg desogestrol), metforminXR (2,000 mg), or both (Combined). The primary outcome, assessed by intention-to-treat analysis, was the effect of the different treatment groups on the prevalence of MetS at the end of study. The analytical model included site, race, and the presence or absence of MetS at the screening visit as covariates. The secondary outcomes included changes in each component of MetS (TG, HDL-C, BP, WC, and fasting glucose levels) over the study period. Of the 240 participants randomly assigned, 20 out of 79 in the COCP group, 16 out of 81 in the metformin group, and 17 out of 80 in the combined group dropped out of the study. A total of 169 participants (70.4%) completed the trial between January 2018 and June 2023 (mean age: 29.5 years; mean BMI: 35.6 kg/m2; 70% were White and 23% were Black). The overall prevalence of MetS was 31% at baseline and comparable across groups. At the end of the study, the prevalence of MetS was 26.2% (17/65) in the metformin group, 28.6% (17/59) in the Combined group, and 28.8% (17/59) in COCP group with no significant difference in trend of MetS prevalence between groups (adjusted p = 0.26). Waist circumference (mean change (MC) -2.23 cm; 95% CI [-3.98, -0.49]; p = 0.01), BMI (MC -0.49 kg/m2; 95% CI [-0.88, -0.10]; p = 0.01), and android fat mass measured by DXA (MC -167 g; 95% CI [-264, -71[; p < 0.001) decreased in the COCP group over the study period whilst there was no statistically significant changes in these parameters in the metformin only group when compared to baseline.. In the metformin and Combined groups, the majority of participants (>64%) reported diarrhea, while 24.1% in the COCP group reported uterine bleeding. The main methodologic limitation of the study is the potential lack of power to detect differences in secondary outcomes.</p><p><strong>Conclusions: </strong>In participants with hyperandrogenic PCOS and overweight/obesity, low-dose COCPs effectively managed PCOS symptoms without increasing prevalence of MetS. Ou
背景:使用联合口服避孕药和/或二甲双胍综合治疗肥胖女性多囊卵巢综合征(PCOS)的风险-效益比尚不清楚。由于缺乏关于这些一线药物对心血管疾病(CVD)风险影响的有力证据,我们比较了COCPs、二甲双胍或两者对高雄激素性PCOS患者代谢综合征(MetS)患病率的影响,并假设COCPs会增加MetS的患病率,而二甲双胍会降低MetS的患病率。方法和研究结果:我们对年龄≥18岁至≤40岁、体重指数(BMI)≥25 kg/m2和≤48 kg/m2伴有高雄激素性PCOS(由鹿特丹标准定义)的参与者进行了一项多中心、双盲、双虚拟、随机试验(COMET-PCOS)。参与者以1:1:1的比例随机分配至24周的低剂量cocp (20 μg炔雌醇/0.15 mg地孕酮)、二甲双胍xr (2,000 mg)或两者(联合)。通过意向治疗分析评估的主要结果是研究结束时不同治疗组对MetS患病率的影响。分析模型包括地点、种族和筛查时是否存在MetS作为协变量。次要结果包括研究期间代谢当量(TG、HDL-C、BP、WC和空腹血糖水平)各组成部分的变化。在随机分配的240名参与者中,COCP组的79人中有20人,二甲双胍组的81人中有16人,联合组的80人中有17人退出了研究。在2018年1月至2023年6月期间,共有169名参与者(70.4%)完成了试验(平均年龄:29.5岁;平均BMI: 35.6 kg/m2; 70%为白人,23%为黑人)。基线时met的总体患病率为31%,各组间具有可比性。研究结束时,二甲双胍组MetS患病率为26.2%(17/65),联合用药组为28.6% (17/59),COCP组为28.8%(17/59),组间MetS患病率趋势无显著差异(调整p = 0.26)。腰围(平均变化(MC) -2.23 cm;95% ci [-3.98, -0.49];p = 0.01), BMI (MC -0.49 kg/m2; 95% CI [-0.88, -0.10]; p = 0.01)和DXA测量的android脂肪量(MC -167 g; 95% CI [-264, -71]; p 64%)报告腹泻,而COCP组有24.1%报告子宫出血。该研究的主要方法学局限性是可能缺乏检测次要结局差异的能力。结论:在高雄激素性多囊卵巢综合征和超重/肥胖的参与者中,低剂量的cocp可以有效地控制多囊卵巢综合征症状,而不会增加MetS的患病率。我们的研究结果挑战了目前单独使用二甲双胍或与cocp一起使用以降低心脏代谢风险的做法。试验注册:临床试验。政府标识符:NCT03229057。
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引用次数: 0
Wildfire-related PM2.5 and respiratory transmitted disease among Chinese children and adolescents from 2008 to 2019: A retrospective study. 2008 - 2019年中国儿童和青少年野火相关PM2.5与呼吸道传播疾病的回顾性研究
IF 9.9 1区 医学 Q1 Medicine Pub Date : 2025-12-05 eCollection Date: 2025-12-01 DOI: 10.1371/journal.pmed.1004613
Li Chen, Rongbin Xu, Junqing Xie, Yi Xing, Bo Wen, Yao Wu, Binbin Su, Mengjie Geng, Xiang Ren, Yi Zhang, Jieyu Liu, Xinli Song, Yang Qin, RuoLin Wang, Jianuo Jiang, Tongjun Guo, Wen Yuan, Yinghua Ma, Yanhui Dong, Yi Song, Jun Ma, Shanshan Li, Yuming Guo
<p><strong>Background: </strong>Exposure to fine particles (PM2.5) from wildfires is known to cause deaths and chronic diseases, but its effect on respiratory infections, especially in children and adolescents, is not well characterized. We aimed to comprehensively assess the association between short-term exposure to wildfire-related PM2.5 and the incidence and mortality of respiratory transmitted diseases in children and adolescents.</p><p><strong>Methods and findings: </strong>Data on daily counts of incident and mortality cases of respiratory transmitted diseases in persons aged 4-24 years old were collected from China Information System for Disease Control and Prevention, covering 501 cities from 2008 to 2019. Daily concentrations of wildfire-related PM2.5 were estimated using machine learning and chemical transport models at a 0.25°×0.25° spatial resolution. We used time-stratified case-crossover design with conditional logistic regression to estimate the association between short-term exposures to wildfire-related PM2.5 and incidence and mortality of respiratory transmitted diseases, adjusting for temperature, relative humidity, precipitation, and total PM2.5. There were 6,089,271 incident cases and 1,034 mortality cases of 10 respiratory transmitted diseases included in our analyses. Each 5 μg/m3 increase in the lag 0-28-day (average of current day and previous 28 days) for wildfire-related PM2.5 was associated with a 6.8% (95%CI: 5.0%, 8.7%) increase in the daily incidence rate of respiratory transmitted diseases, which is greater than that of a 1.2% (1.0%, 1.4%) increase associated with the same increase of non-wildfire-related PM2.5. A 5 μg/m3 increase in wildfire-related PM2.5 was associated with a 28.6% (21.0%, 36.8%), 5.2% (2.3%, 8.3%), 12.6% (9.5%, 15.8%), and 13.6% (5.6%, 22.2%) increase in the incidence of seasonal influenza, scarlet fever, rubella, and measles, respectively. Although wildfire-related PM2.5 constitutes only 2.7% of the total PM2.5, it contributes significantly to respiratory transmitted diseases, accounting for 10.8% of all PM2.5-associated cases. In areas where the annual concentration of wildfire-related PM2.5 is lower than 1.5 μg/m3, the proportion of cases associated with wildfire-related PM2.5 reached 29.7%. Study limitations include potential exposure misclassification from using city-average wildfire PM2.5 as a proxy for individual exposure and an inability to adjust for some potential confounders.</p><p><strong>Conclusions: </strong>Short-term exposure to wildfire-related PM2.5 was associated with increased incidence of respiratory transmitted diseases, surpassing the impact observed with non-wildfire-related PM2.5. This phenomenon is not restricted to regions with high pollutant concentrations; even populations residing in areas with lower concentrations of wildfire-related PM2.5 are at an increased risk of these respiratory conditions. Consequently, there emerges a pressing global imperative to confront
背景:已知暴露于野火产生的细颗粒物(PM2.5)会导致死亡和慢性疾病,但其对呼吸道感染的影响,特别是对儿童和青少年的影响尚未得到很好的描述。我们的目的是全面评估短期暴露于野火相关PM2.5与儿童和青少年呼吸道传播疾病的发病率和死亡率之间的关系。方法与结果:收集中国疾病预防控制信息系统2008 - 2019年501个城市4-24岁人群呼吸道传播疾病日发病和死亡病例数数据。利用机器学习和化学传输模型,在0.25°×0.25°空间分辨率下估算了与野火相关的PM2.5的日浓度。我们采用时间分层病例交叉设计和条件logistic回归来估计短期暴露于野火相关PM2.5与呼吸道传播疾病发病率和死亡率之间的关系,调整温度、相对湿度、降水和PM2.5总量。10种呼吸道传播疾病共6089271例,死亡1034例。在0-28天(当日和前28天的平均值)内,与野火相关的PM2.5每增加5 μg/m3,呼吸道传播疾病的日发病率就会增加6.8% (95%CI: 5.0%, 8.7%),高于与非野火相关的PM2.5同样增加1.2%(1.0%,1.4%)。与野火相关的PM2.5浓度每增加5 μg/m3,季节性流感、猩红热、风疹和麻疹的发病率分别增加28.6%(21.0%、36.8%)、5.2%(2.3%、8.3%)、12.6%(9.5%、15.8%)和13.6%(5.6%、22.2%)。虽然野火相关的PM2.5仅占PM2.5总量的2.7%,但它对呼吸道传播疾病的贡献很大,占所有PM2.5相关病例的10.8%。在林火相关PM2.5年浓度低于1.5 μg/m3的地区,林火相关PM2.5病例占比达到29.7%。研究的局限性包括使用城市平均野火PM2.5作为个人暴露的代表而对潜在的暴露进行错误分类,以及无法调整一些潜在的混杂因素。结论:短期暴露于野火相关的PM2.5与呼吸道传播疾病的发病率增加相关,超过了非野火相关的PM2.5所观察到的影响。这种现象并不局限于污染物浓度高的地区;即使是居住在与野火有关的PM2.5浓度较低地区的人群,患这些呼吸系统疾病的风险也会增加。因此,全球迫切需要应对气候变化带来的不断升级的挑战和日益加剧的野火威胁。
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引用次数: 0
Ultrasensitive quantification of serum IFN-α and IFN-γ in systemic lupus erythematosus: A cross-sectional observational study. 系统性红斑狼疮患者血清IFN-α和IFN-γ的超灵敏定量测定:一项横断面观察研究。
IF 9.9 1区 医学 Q1 Medicine Pub Date : 2025-12-05 eCollection Date: 2025-12-01 DOI: 10.1371/journal.pmed.1004841
Miguel Á González-Gay, Fuensanta Gómez-Bernal, Juan C Quevedo-Abeledo, Cristina Almeida-Santiago, Elena Heras-Recuero, Arantxa Torres-Roselló, Antonia de Vera-González, Beatriz Tejera-Segura, Enrique García-Barrera, Teresa Blázquez-Sánchez, Luisa M Villar, Javier Gonzalo Ocejo-Vinyals, Raquel Largo, Iván Ferraz-Amaro
<p><strong>Background: </strong>Interferon (IFN) has been implicated in the pathogenesis of patients with systemic lupus erythematosus (SLE). However, its measurement in serum has been limited by low circulating levels that fall below the detection threshold of standard laboratory assays. In this study, we measured serum levels of IFN-alpha (IFN-α) and IFN-gamma (IFN-γ) using a novel ultrasensitive assay. We then aimed to analyze the relationship between these IFN levels and a broad spectrum of disease characteristics, including indices of disease activity and remission, and autoantibodies profiles.</p><p><strong>Methods and findings: </strong>From an initial cohort of 400 patients, a total of 313 patients with SLE were recruited in this cross-sectional study from September 2023 to February 2024. A comprehensive characterization of the patients was performed, including autoantibody profiles and indices of disease activity (SLE-DAS, SLEDAI-2K, and LLDAS), damage (SLICC-DI), and remission (DORIS). IFN-α and IFN-γ serum levels were measured using Simoa (Single Molecule Array) technique. A multivariable linear regression analysis was performed to examine the associations between the disease characteristics and circulating IFN-α and IFN-γ as the dependent variables. Besides, the diagnostic capacity of serum IFN levels to discriminate between high and low disease activity was studied using area under the curve analysis and determination of optimal cutoff points. Serum levels of IFN-α and IFN-γ showed a significant, albeit weak, correlation (Pearson's r = 0.369, p < 0.001). Both IFNs exhibited minimal associations with demographic characteristics (such as age, sex, and body mass index) and traditional cardiovascular risk factors (including hypertension, diabetes, dyslipidemia, smoking status, obesity, and metabolic syndrome). After multivariable adjustment, IFN-α-but not IFN-γ-was significantly and positively associated with acute-phase reactants (C-reactive protein and interleukin-6), disease activity indices (SLEDAI-2K, beta coefficient: 0.20 [95% confidence interval 0.09, 0.32] log pg/ml, p < 0.001 and SLE-DAS, beta coefficient: 0.15 [95% confidence interval 0.05, 0.25] log pg/ml, p = 0.003) and the presence of antinuclear antibodies. In contrast, remission (as defined by DORIS) and low disease activity (LLDAS) were negatively and significantly associated with IFN-α levels after adjustment for covariates. However, when attempts were made to define IFN cutoff values to discriminate between active and inactive disease or remission, they exhibited a poor balance between sensitivity and specificity. The cross-sectional design of this study limits our ability to infer causality and raises the possibility of reverse causation.</p><p><strong>Conclusions: </strong>In this study, we observed that IFN-α, but not IFN-γ, significantly associates with inflammation, indices of disease activity and remission, and autoantibody status in SLE. Investigating the potent
背景:干扰素(IFN)与系统性红斑狼疮(SLE)患者的发病机制有关。然而,其在血清中的测量受到低循环水平的限制,低于标准实验室测定的检测阈值。在这项研究中,我们使用一种新的超灵敏检测方法测量了血清中IFN-α (IFN-α)和IFN-γ (IFN-γ)的水平。然后,我们旨在分析这些IFN水平与广泛的疾病特征之间的关系,包括疾病活动性和缓解指数,以及自身抗体谱。方法和发现:从最初的400例患者队列中,在2023年9月至2024年2月的横断面研究中共招募了313例SLE患者。对患者进行了全面的表征,包括自身抗体谱和疾病活动性指数(sledi - das、SLEDAI-2K和LLDAS)、损伤(SLICC-DI)和缓解(DORIS)。采用Simoa(单分子阵列)技术检测血清中IFN-α和IFN-γ水平。进行多变量线性回归分析,以检验疾病特征与循环IFN-α和IFN-γ作为因变量之间的关系。此外,通过曲线下面积分析和最佳截断点的确定,研究了血清IFN水平对疾病活动性高低的诊断能力。血清中IFN-α和IFN-γ水平显示出显著的相关性,尽管相关性较弱(Pearson’s r = 0.369, p)。结论:在本研究中,我们观察到IFN-α,而非IFN-γ,与SLE的炎症、疾病活动性和缓解指标以及自身抗体状态显著相关。研究IFN-α作为治疗反应和长期结果的生物标志物的潜力是有必要的。
{"title":"Ultrasensitive quantification of serum IFN-α and IFN-γ in systemic lupus erythematosus: A cross-sectional observational study.","authors":"Miguel Á González-Gay, Fuensanta Gómez-Bernal, Juan C Quevedo-Abeledo, Cristina Almeida-Santiago, Elena Heras-Recuero, Arantxa Torres-Roselló, Antonia de Vera-González, Beatriz Tejera-Segura, Enrique García-Barrera, Teresa Blázquez-Sánchez, Luisa M Villar, Javier Gonzalo Ocejo-Vinyals, Raquel Largo, Iván Ferraz-Amaro","doi":"10.1371/journal.pmed.1004841","DOIUrl":"10.1371/journal.pmed.1004841","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Interferon (IFN) has been implicated in the pathogenesis of patients with systemic lupus erythematosus (SLE). However, its measurement in serum has been limited by low circulating levels that fall below the detection threshold of standard laboratory assays. In this study, we measured serum levels of IFN-alpha (IFN-α) and IFN-gamma (IFN-γ) using a novel ultrasensitive assay. We then aimed to analyze the relationship between these IFN levels and a broad spectrum of disease characteristics, including indices of disease activity and remission, and autoantibodies profiles.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;From an initial cohort of 400 patients, a total of 313 patients with SLE were recruited in this cross-sectional study from September 2023 to February 2024. A comprehensive characterization of the patients was performed, including autoantibody profiles and indices of disease activity (SLE-DAS, SLEDAI-2K, and LLDAS), damage (SLICC-DI), and remission (DORIS). IFN-α and IFN-γ serum levels were measured using Simoa (Single Molecule Array) technique. A multivariable linear regression analysis was performed to examine the associations between the disease characteristics and circulating IFN-α and IFN-γ as the dependent variables. Besides, the diagnostic capacity of serum IFN levels to discriminate between high and low disease activity was studied using area under the curve analysis and determination of optimal cutoff points. Serum levels of IFN-α and IFN-γ showed a significant, albeit weak, correlation (Pearson's r = 0.369, p &lt; 0.001). Both IFNs exhibited minimal associations with demographic characteristics (such as age, sex, and body mass index) and traditional cardiovascular risk factors (including hypertension, diabetes, dyslipidemia, smoking status, obesity, and metabolic syndrome). After multivariable adjustment, IFN-α-but not IFN-γ-was significantly and positively associated with acute-phase reactants (C-reactive protein and interleukin-6), disease activity indices (SLEDAI-2K, beta coefficient: 0.20 [95% confidence interval 0.09, 0.32] log pg/ml, p &lt; 0.001 and SLE-DAS, beta coefficient: 0.15 [95% confidence interval 0.05, 0.25] log pg/ml, p = 0.003) and the presence of antinuclear antibodies. In contrast, remission (as defined by DORIS) and low disease activity (LLDAS) were negatively and significantly associated with IFN-α levels after adjustment for covariates. However, when attempts were made to define IFN cutoff values to discriminate between active and inactive disease or remission, they exhibited a poor balance between sensitivity and specificity. The cross-sectional design of this study limits our ability to infer causality and raises the possibility of reverse causation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;In this study, we observed that IFN-α, but not IFN-γ, significantly associates with inflammation, indices of disease activity and remission, and autoantibody status in SLE. Investigating the potent","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 12","pages":"e1004841"},"PeriodicalIF":9.9,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12680241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Setting the standard for high-quality studies using open health datasets. 制定使用开放卫生数据集进行高质量研究的标准。
IF 9.9 1区 医学 Q1 Medicine Pub Date : 2025-12-04 eCollection Date: 2025-12-01 DOI: 10.1371/journal.pmed.1004854
Andreia Cunha, Suzanne de Bruijn, Alison Farrell, Helen Lumbard, Alexandra Tosun, Daniel Routledge

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.

大型开放卫生数据集为研究提供了独特的机会,如果设计、实施和报告良好,可以为卫生和医学提供宝贵的贡献。然而,近年来出现了大量缺乏可靠或新颖发现的分析。在这篇社论中,我们为作者使用这些数据集进行和报告高质量的二次分析提供指导。
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引用次数: 0
Association of hydralazine use with risk of hematologic neoplasms in patients with hypertension: A nationwide population-based cohort study in Taiwan. 高血压患者使用肼嗪与血液肿瘤风险的关系:台湾一项全国性人群队列研究。
IF 9.9 1区 医学 Q1 Medicine Pub Date : 2025-12-04 eCollection Date: 2025-12-01 DOI: 10.1371/journal.pmed.1004646
Li-Tzu Wang, Wu-Chien Chien, Kevin Sheng-Kai Ma, Chi-Hsiang Chung, Yeu-Chin Chen, Wei-Che Tsai, Bing-Heng Yang

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.

背景:Onco-hypertension认识到良好控制的血压是高血压和实体肿瘤(包括血液肿瘤)患者生存的有利预后因素。然而,与其他降压药相比,持续使用肼嗪(一种具有显著抗肿瘤活性的降压药)是否与较低的血液病肿瘤风险相关尚不清楚。​高血压患者根据肼嗪处方持续时间分为两组:暴露组(肼嗪≥180天;n = 59,786)和参照组(肼嗪)。结论:在本研究中,我们观察到高血压患者长期使用肼嗪与较低的、持续时间依赖的血液肿瘤风险相关。这些发现需要前瞻性研究来证实这种关联及其潜在的临床意义。
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引用次数: 0
Social and health system factors associated with maternal mortality in Eastern and Western China: Population health estimates using provincial-level data. 与中国东部和西部孕产妇死亡率相关的社会和卫生系统因素:使用省级数据的人口健康估算
IF 9.9 1区 医学 Q1 Medicine Pub Date : 2025-12-04 eCollection Date: 2025-12-01 DOI: 10.1371/journal.pmed.1004837
Xiaojing Zeng, Dongjian Yang, Shiyang Li, Xiaolin Hua, Yanlin Wang, Jun Zhang, Zhiwei Liu

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.

背景:在全球范围内,孕产妇死亡率偏离了到2030年实现可持续发展目标的轨道。在过去的二十年里,中国大大降低了较发达(东部)和欠发达(西部)地区的孕产妇死亡率。了解与中国孕产妇死亡率相关的社会和卫生系统因素可能有助于各国实现2030年及以后的目标。方法与结果:分析2004 - 2020年《国家卫生统计年鉴》和《中国统计年鉴》中各省孕产妇死亡率和社会卫生系统因素数据。我们调查了2013年前后与孕产妇死亡率相关的因素,2013年是一个历史性的国家项目“降低孕产妇死亡率和消除新生儿破伤风”结束的一年。采用贝叶斯核机回归分析社会卫生系统因素(城镇化率、人均可支配收入、平均受教育年限、妇幼保健卫生技术人员数量、妇产科医院床位数、地方财政卫生保健支出、产前预约率、产前保健率、和住院分娩率)作为混合物,并确定具有较大后验包含概率和较高的暴露-反应关系值的因素对总和原因特异性产妇死亡率。在东部地区,2013年前住院分娩率的提高与孕产妇总死亡率的降低相关[后验均值和标准差(SD): -14.8(1.5)], 2013年后城镇化率与孕产妇总死亡率呈负相关[后验均值和标准差:-3.9(0.6)]。在东方,医院分娩、城市化、地方财政保健支出和产前保健是降低特定原因产妇死亡率的相关因素。在西方,产前保健率的增加与孕产妇总死亡率的降低相关,2013年前后的后验均值和标准差分别为-33.8(6.8)和-11.5(4.1)。在西方,医院分娩和产前护理是降低特定原因产妇死亡率的相关因素。本研究的主要局限性是国家统计数据的限制。结论:2004-2020年期间,孕产妇保健覆盖、卫生筹资和城市化是中国东部和西部孕产妇死亡率大幅下降的相关因素。提高产前保健和住院分娩的数量和质量可能是全世界欠发达地区的一项可行的优先政策。
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引用次数: 0
Hospital-based care for hallucinogens and risk of mania and bipolar disorder: A population-based cohort study. 致幻剂的医院护理与躁狂症和双相情感障碍的风险:一项基于人群的队列研究
IF 9.9 1区 医学 Q1 Medicine Pub Date : 2025-12-02 eCollection Date: 2025-12-01 DOI: 10.1371/journal.pmed.1004805
Daniel T Myran, Rachael MacDonald-Spracklin, Michael Pugliese, Maya Gibb, Jess G Fiedorowicz, Tyler S Kaster, Marco Solmi

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.

背景:用于娱乐和医疗目的的致幻剂在全球范围内迅速增加,引起了对潜在副作用的关注。本研究调查了突发躁狂症或双相情感障碍(BD)诊断与急诊室(ED)就诊或使用致幻剂住院相关的风险。方法和研究结果:我们采用了一项基于人群的队列研究,所有年龄在14-65岁之间,没有基线BD病史,并在加拿大安大略省的安大略省健康保险计划中登记,时间为2008-2022年。使用重叠倾向评分加权Cox比例风险模型,比较使用致幻剂的急性护理(急诊科就诊或住院)个体和一般人群的偶发性躁狂症(主要结局)和偶发性双相障碍(次要结局)。模型根据年龄、性别、农村住所、收入五分位数、最近无家可归的记录以及过去五年因精神健康或其他物质使用而就诊的医疗记录进行了调整。该研究包括9,311,844人,其中7,285人(0.08%)接受过涉及致幻剂的急性护理。在使用致幻剂的3年内,1.43% (n = 104)的个体出现了需要急性治疗的躁狂发作,而在年龄性别匹配的普通人群中,这一比例为0.06% (n = 41),风险增加了25倍。加权后,服用致幻剂的急性护理与没有服用致幻剂的个体相比,发生躁狂的风险增加了6倍(加权风险比[HR] 5.97, 95% CI 3.29, 10.82),而这些个体在其他方面具有相似的人口统计学和精神健康史。相关的双相障碍诊断风险也增加(HR 3.75 95%CI 2.49, 5.65,绝对比例2.50%对0.11%)。该研究的主要局限性是,与本研究中所检查的暴露相关的风险可能不会推广到大多数不需要急性护理的致幻剂使用者。结论:这些发现提示有双相情感障碍风险的个体使用致幻剂需要持续谨慎。它们还对临床实践、研究和公共卫生政策具有潜在影响,包括在致幻剂使用不断增加的背景下对高危人群进行物质管制和有针对性的教育。
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引用次数: 0
Treatment and prevention of HIV/AIDS: Unfinished business. 艾滋病毒/艾滋病的治疗和预防:未完成的事业。
IF 9.9 1区 医学 Q1 Medicine Pub Date : 2025-12-01 DOI: 10.1371/journal.pmed.1004806
Anthony S Fauci, Gregory K Folkers

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.

自1988年设立世界艾滋病日以来,抗逆转录病毒药物的进展彻底改变了艾滋病毒/艾滋病治疗和预防的格局。在2025年,我们回顾已取得的进展,强调有希望的治疗进展,并展望终结艾滋病流行所需的工作。
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引用次数: 0
The impact of adherence on colorectal cancer screening cost-effectiveness: A modeling study. 依从性对结直肠癌筛查成本-效果的影响:一项模型研究。
IF 9.9 1区 医学 Q1 Medicine Pub Date : 2025-11-26 eCollection Date: 2025-11-01 DOI: 10.1371/journal.pmed.1004807
Jiaxin Xie, Xuesi Dong, Zilin Luo, Chenran Wang, Yadi Zheng, Xiaolu Chen, Zeming Guo, Xiaoyue Shi, Fei Wang, Wei Cao, Yongjie Xu, Le Wang, Weimiao Wu, Dong Hang, Lingbin Du, Ni Li
<p><strong>Background: </strong>Adherence to colorectal cancer (CRC) screening remains suboptimal in many countries, reducing its cost-effectiveness. This study aimed to evaluate how multistage uptake rates influence the health benefit and cost-effectiveness of various CRC screening strategies in the Chinese population, incorporating both traditional and emerging screening methods.</p><p><strong>Methods and findings: </strong>We developed a multistate Markov model (CRC-SIM) to evaluate the impact of multistep uptake on CRC screening. A hypothetical cohort of 100,000 individuals aged 40 was simulated and followed until 79 or death. Two-step screening strategies were modeled: initial screening followed by colonoscopy after a positive result. Traditional initial screening methods include: questionnaire-based risk assessment, fecal immunochemical test (FIT), and questionnaire combined with FIT; Non-invasive biomarker-based initial strategies include a hypothetical test meeting the minimum standards of China National Medical Products Administration (NMPAmin), multitarget stool DNA (mt-sDNA) test, and blood-based strategies. All strategies were modeled as one-time screenings, with outcomes projected for CRC cases, deaths, quality-adjusted life years (QALYs), and lifetime costs. Incremental cost-effectiveness ratios (ICERs) were calculated, and a cost-effectiveness heatmap was conducted to assess the impact of multistep uptake (modeled in 10% steps) on economic outcomes. All strategies reduced CRC cases, deaths and increased QALYs compared to no screening, with biomarker-based strategies outperforming the traditional methods at the same uptake level (e.g., questionnaire combined with FIT prevented 224 (95% confidence interval (CI) [157, 292]) CRC cases and 151 (95% CI [109, 195]) deaths, whereas NMPAmin prevented 312 (95% CI [257, 360]) cases and 210 (95% CI [175, 241]) deaths at 100% uptake). The cost-effectiveness heatmap indicated that each 10% increase in initial and follow-up colonoscopy uptake improved ICERs in a non-linear pattern. The questionnaire combined with FIT was the most cost-effective strategy (ICER = $2,413 per QALY gained). Non-invasive biomarker-based tests were not cost-effective compared with the combined questionnaire and FIT strategy under current assumptions of test costs and identical uptake rate. Threshold analysis showed that non-invasive biomarker-based screening would become cost-effective if test costs fell below $131.7 or colonoscopy uptake increased to at least 70% for NMPAmin and 50% for blood-based tests and mt-sDNA. Limitations include the assumption of a one-time screening scenario; future iterations of the model and merging evidence in repeated screening will address these limitations.</p><p><strong>Conclusion: </strong>Improving screening participation could enhance health benefits and cost-efficiency in CRC screening. Questionnaire-based risk assessment combined with FIT was a cost-effective strategy in China, whe
背景:在许多国家,对结直肠癌(CRC)筛查的依从性仍然不够理想,降低了其成本效益。本研究旨在评估多阶段摄取率如何影响中国人群中各种CRC筛查策略的健康效益和成本效益,包括传统和新兴筛查方法。方法和发现:我们建立了一个多状态马尔可夫模型(CRC- sim)来评估多步骤摄取对CRC筛查的影响。研究人员对10万名年龄在40岁的人进行了模拟,并对他们进行了随访,直到79岁或死亡。模拟两步筛查策略:初步筛查,阳性结果后进行结肠镜检查。传统的初步筛查方法包括:基于问卷的风险评估、粪便免疫化学试验(FIT)、问卷与FIT相结合;基于非侵入性生物标志物的初始策略包括符合中国国家药品监督管理局(NMPAmin)最低标准的假设测试、多靶点粪便DNA (mt-sDNA)测试和基于血液的策略。所有策略均以一次性筛查为模型,预测结直肠癌病例、死亡、质量调整生命年(QALYs)和终生成本的结果。计算了增量成本效益比(ICERs),并进行了成本效益热图,以评估多步骤吸收(以10%的步骤建模)对经济结果的影响。与没有筛查相比,所有策略都减少了CRC病例、死亡和增加了QALYs,在相同摄取水平下,基于生物标志物的策略优于传统方法(例如,问卷结合FIT预防了224例(95%置信区间(CI) [157, 292]) CRC病例和151例(95% CI[109, 195])死亡,而NMPAmin在100%摄取时预防了312例(95% CI[257, 360])和210例(95% CI[175, 241])死亡)。成本-效果热图显示,初次和随访结肠镜检查每增加10%,ICERs均呈非线性模式改善。问卷结合FIT是最具成本效益的策略(ICER = $2,413 / QALY)。在目前的测试成本和相同的吸收率假设下,与联合问卷和FIT策略相比,基于非侵入性生物标志物的测试不具有成本效益。阈值分析表明,如果检测成本降至131.7美元以下,或者结肠镜检查NMPAmin的使用率至少提高到70%,血液检测和mt-sDNA的使用率至少提高到50%,基于生物标志物的非侵入性筛查将具有成本效益。局限性包括假设一次性筛选方案;模型的未来迭代和在重复筛选中合并证据将解决这些局限性。结论:提高筛查参与率可提高CRC筛查的健康效益和成本效益。在中国,基于问卷的风险评估与FIT相结合是一种具有成本效益的策略,而基于非侵入性生物标志物的方法需要降低成本和提高采用率来证明采用的合理性。这些发现为决策者优化CRC筛查方案提供了依据。
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引用次数: 0
Global Burden of Disease 2023: Challenges and opportunities for a growing collaboration. 《2023年全球疾病负担:加强合作的挑战和机遇》。
IF 9.9 1区 医学 Q1 Medicine Pub Date : 2025-11-26 eCollection Date: 2025-11-01 DOI: 10.1371/journal.pmed.1004838
Zulfiqar A Bhutta

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.

《2023年全球疾病负担》是自1993年首次报告以来同类报告中最全面的一次。尽管改进了健康监测、数据获取和分析方法,但其扩展为提高其准确性、完整性、外部有效性和政策相关性带来了新的挑战和机遇。
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引用次数: 0
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