PLoS Medicine最新文献

{"title":"Correction: Reassessing BMI-based access to joint replacement surgery.","authors":"","doi":"10.1371/journal.pmed.1005076","DOIUrl":"10.1371/journal.pmed.1005076","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1371/journal.pmed.1005003.].</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"23 4","pages":"e1005076"},"PeriodicalIF":9.9,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786711","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}

{"title":"The principles of Population-Level Approaches to Dementia Risk Reduction (PLADRR).","authors":"Sebastian Walsh, Susanne Röhr, Joaquin Mígeot, Yuliya Bodryzlova, Etuini Ma'u, Simone Salemme, Charles R Marshall, Timothy Daly, Gary Cheung, Blossom C M Stephan, Raj Kalaria, Kenneth M Langa, Naaheed Mukadam, Leslie Grasset, Sarah Cullum, Ishtar Govia, Nikki-Anne Wilson, Daniele Urso, Ruth Peters, Jingxuan Wang, Edo Richard, Giancarlo Logroscino, Stefano Giannoni-Luza, Nicola T Lautenschlager, Josephine E Prynn, Cleusa P Ferri, Susan Yates, Frank J Wolters, Lindsay Wallace, Carol Brayne, Kaarin J Anstey","doi":"10.1371/journal.pmed.1005059","DOIUrl":"https://doi.org/10.1371/journal.pmed.1005059","url":null,"abstract":"<p><p>Dementia is a leading health policy challenge, with cases expected to triple by 2050, particularly in low- and middle-income countries. Epidemiological evidence demonstrates falling age-specific incidence rates in high-income countries, suggesting risk can be lowered at the population level.The Population-Level Approaches to Dementia Risk Reduction (PLADRR) Research Group is a diverse, international network of researchers committed to investigating how structural, social, and environmental conditions can promote life course brain health and reduce dementia risk across the population.This Policy Forum article sets out the guiding principles of our approach, the building blocks required, our research priorities, and how PLADRR research can inform and translate into policy changes.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"23 4","pages":"e1005059"},"PeriodicalIF":9.9,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13123963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786785","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}

{"title":"Identifying novel prodromal symptoms of eclampsia: A two-country, case-control study.","authors":"Roxanne Hastie, Farhatulain Ahmed, Parinaz Mehdipour, Bernard Yan, Susan P Walker, Jacqui Visser, Anam Bashir, Lyle Gurrin, Anthea Lindquist, Jessica A Atkinson, Catherine Cluver, Lina Bergman, Stephen Tong","doi":"10.1371/journal.pmed.1004994","DOIUrl":"https://doi.org/10.1371/journal.pmed.1004994","url":null,"abstract":"<p><strong>Background: </strong>Magnesium sulphate halves the risk of eclampsia. There is no consensus on who to give magnesium sulphate prophylaxis because clinical tools are poor at identifying those at risk. Known prodromal symptoms such as headache, visual disturbance, or epigastric pain have modest associations with eclampsia. We set out to identify new prodromal symptoms of eclampsia.</p><p><strong>Methods and findings: </strong>This case-control study prospectively recruited participants in South Africa and Pakistan who had eclampsia, preeclampsia, or normotensive pregnancies. We asked whether they experienced 20 neurological symptoms, within 7 days of the seizure for those who had eclampsia. The primary analysis was the likelihood of symptoms occurring before eclampsia, compared to being present with preeclampsia. 341 participants were recruited with eclampsia, 1,355 with preeclampsia and 389 with normotensive pregnancies. When comparing symptoms among those who had eclampsia versus preeclampsia, the odds ratios (OR) were 2.56 (95% confidence interval (CI) [1.81,3.62]; p < 0.001) for headache, 5.73 (95% CI [4.44,7.39]; p < 0.001) for visual disturbances and 2.25 (95% CI [1.76,2.89]; p < 0.001) for epigastric pain. We identified 10 symptoms with odds ratios over 10 for eclampsia. Odds ratios were 42.03 (95% CI [23.66,74.68]; p < 0.001) for twitching/jerking limbs (30.5% eclampsia versus 1% preeclampsia); 36.00 (95% CI [18.34,70.65]; p < 0.001) for affected hearing (21.1% versus 0.7%)' 33.60 (95% CI [21.39,52.78]; p < 0.001) for affected mind state (38.7% versus 1.8%); 33.12 (95% CI [19.46, 54.37]; p < 0.001) for impaired speech; 23.71 (95% CI [16.49,34.10]; p < 0.001) for feelings of doom; 26.59 (95% CI [7.82,90.41]; p < 0.001) for severe vertigo; 20.52 (95% CI [14.22,29.63]; p < 0.001) for confusion; 18.16 (95% CI [10.76,30.66]; p < 0.001) for jitters; 15.18 (95% CI [11.34,20.33]; p < 0.001) for difficulty concentrating; and 10.49 (95% CI [6.76,16.27]; p < 0.001) for weakness/paralysis. These symptoms were rare among normotensive pregnancies. Only 2.4% of women with eclampsia did not experience any prodromal symptoms. This study is limited by the fact that we asked about prodromal symptoms after the seizure happened, and the potential for recall bias.</p><p><strong>Conclusions: </strong>Ten prodromal symptoms exhibit far stronger associations with eclampsia than headache, visual disturbances, or epigastric pain. Eclampsia is uncommon without any prodromal symptoms. It may be useful to screen these symptoms among women with preeclampsia as part of clinical history taking to guide management. They could help direct magnesium sulphate prophylaxis to those with a higher risk of eclampsia.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"23 4","pages":"e1004994"},"PeriodicalIF":9.9,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13123989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786760","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}

{"title":"Subsequent primary cancer incidence among cancer survivors in the United States, 1975-2019: An age-period-cohort analysis.","authors":"Hui G Cheng, Livingstone Aduse-Poku, Chelsey McGill, Oxana Palesh, Susan Hong","doi":"10.1371/journal.pmed.1005034","DOIUrl":"https://doi.org/10.1371/journal.pmed.1005034","url":null,"abstract":"<p><strong>Background: </strong>The growing population of cancer survivors faces elevated risks of subsequent primary cancers (SPCs), yet temporal patterns in SPC incidence remain poorly understood. This study aims to characterize age-, period-, and cohort-specific patterns in SPC incidence among US cancer survivors using population-based data.</p><p><strong>Methods and findings: </strong>We conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) 8 registries, identifying 3.36 million individuals diagnosed with a first primary cancer between 1975 and 2019. Survivors were followed through 2022 to estimate the incidence of SPCs. We used age-period-cohort analysis to estimate longitudinal age curves, cohort and period rate ratios, and annual percent changes in SPC incidence. Analyses were stratified by sex and the five most common index cancer sites. During 29.5 million person‑years of follow‑up, 510,340 SPCs were observed. SPC incidence increased with age at index cancer diagnosis, rising among females from 915 per 100,000 person‑years at ages 35-39 years to 1,980 per 100,000 at ages 75-79 years, and among males from 1,228 per 100,000 to 2,945 per 100,000 across the same age groups, demonstrating steeper rises in men. Cohort-specific SPC risk peaked in the 1935-1945 birth cohorts and declined in later cohorts, except among female survivors of lung cancer and male survivors of bladder cancer, where risks continued to rise. Period patterns showed overall declines in SPC incidence, particularly among survivors diagnosed at a younger age, but increasing risks among survivors diagnosed at an older age and survivors of specific index cancer sites. Notably, SPC incidence rose by 60% among female lung cancer survivors between 1975-1979 and 2015-2019 (incidence rate ratio = 1.60, 95% CI [1.22, 2.09]; p < 0.001). Main limitations include the descriptive nature of age-period-cohort analyses and the absence of treatment, genetic, and lifestyle data in SEER.</p><p><strong>Conclusions: </strong>SPC risk is shaped by complex, site- and sex-specific temporal patterns. These findings underscore the need for tailored survivorship care strategies that incorporate age, cohort, and index cancer site to mitigate future SPC burden.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"23 4","pages":"e1005034"},"PeriodicalIF":9.9,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13123941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786765","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}

{"title":"Optimizing dengue vaccination strategies.","authors":"Annelies Wilder-Smith","doi":"10.1371/journal.pmed.1005068","DOIUrl":"https://doi.org/10.1371/journal.pmed.1005068","url":null,"abstract":"<p><p>Dengue is a rapidly expanding global health threat driven by urbanization, climate change, and complex transmission dynamics. Modeling and tailored vaccination programs will be critical to developing effective, context-specific strategies to reducing disease burden.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"23 4","pages":"e1005068"},"PeriodicalIF":9.9,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786840","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}

{"title":"Obesity and cancer: Methodological frontiers for mechanistic discoveries.","authors":"Steven C Moore, Patrick J Ryan","doi":"10.1371/journal.pmed.1005081","DOIUrl":"10.1371/journal.pmed.1005081","url":null,"abstract":"<p><p>It has long been a biological mystery why obesity increases cancer risk. Rapid advances in statistical and analytical methods are now opening the door to mechanistic discoveries that may finally resolve this question.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"23 4","pages":"e1005081"},"PeriodicalIF":9.9,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13128105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786827","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}

{"title":"Tobacco control policies on cancer prevention in the Eastern Mediterranean Region, 2025-2050: A modeling study.","authors":"Saeed Nemati, Mojtaba Vand Rajabpour, Xiaoshuang Feng, Negar Taheri, Harriet Rumgay, Farrokh Heidari, Ebrahim Karimi, Sepideh Abdi, Mattias Johansson, Mahdi Sheikh","doi":"10.1371/journal.pmed.1005032","DOIUrl":"https://doi.org/10.1371/journal.pmed.1005032","url":null,"abstract":"<p><strong>Background: </strong>Despite the implementation of control policies, smoking prevalence remains high in Eastern Mediterranean Region (EMR), and the impact of tobacco control efforts on cancer prevention is unclear. We assessed the potential impact of key policy interventions on tobacco-related cancer incidence in EMR countries from 2025 to 2050.</p><p><strong>Methods and findings: </strong>We conducted a modeling study using a country-level historical data to project tobacco smoking prevalence in EMR countries under four scenarios: (i) full implementation of the MPOWER (Monitor, Protection, Offer, Warn, Enforce, and Raise) policy package, (ii) a 10-unit increase in the cigarette affordability index (Higher values of the affordability index indicate that cigarettes are less affordable) (iii) maximized literacy rates (100% adult literacy), and (iv) combined implementation of all three policies. For each scenario, we estimated the Population Attributable Fraction (PAF) of tobacco smoking for 13 cancer types causally linked to tobacco use. The number of preventable cancer cases was calculated using the difference in PAFs between the current and alternative scenarios, referred to as the Potential Impact Fraction (PIF). An estimated 14.3 million tobacco-related cancer cases will occur in the EMR between 2025 and 2050, with over 3 million attributable to current smoking prevalence (PAF = 21.3%; [95% CI: 18.4, 24.6]). Combined implementation of all assessed policies could prevent 442,292 cases (95% CI: 226,987, 660,045) (3.1% of all projected cases; [95% CI: 1.6, 4.6]). The greatest impact was observed in low HDI (Human Development Index) countries, where up to 291,425 (95% CI: 198,186, 388,546) cases could be averted. Maximizing literacy showed the highest preventive potential in low (n = 224,463; [95% CI: 149,521, 307,386]) and medium HDI (n = 84,569; [95% CI: [2,801, 177,317]) countries, while full implementation of MPOWER had the greatest effect in high HDI countries (n = 11,890; [95% CI: 8,397, 15,378]). As our main limitation, we assumed a causal relationship between previously implemented policies and concurrent changes, while other potential causes of these changes have not been considered in the current study.</p><p><strong>Conclusion: </strong>Strengthening tobacco control policies particularly improving literacy in low HDI countries may potentially contribute to reductions in future cancer burden in EMR.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"23 4","pages":"e1005032"},"PeriodicalIF":9.9,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786848","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}

{"title":"Identification of lipid quantitative trait loci linked with cardiometabolic disease in Asian Indians and Europeans: A genome-wide association study and Mendelian randomization.","authors":"Madhusmita Rout, Christopher E Aston, Ravindranath Duggirala, Harald H Goring, Oliver Fiehn, Dharambir K Sanghera","doi":"10.1371/journal.pmed.1005039","DOIUrl":"10.1371/journal.pmed.1005039","url":null,"abstract":"<p><strong>Background: </strong>Genetic mechanisms that predispose people to type 2 diabetes (T2D) and cardiovascular disease (CVD) remain poorly understood, partly because of a lack of sufficient data on non-European ethnic groups. Extending these evaluations to diverse cohorts is essential for gaining insights into the molecular pathways involved in disease development among human populations. In this study, we aimed to evaluate the genetic connection between the human lipidome and cardiometabolic disorders. We conducted a metabolite genome-wide association study (mGWAS) in a Punjabi population from India, along with multi-layer replication studies using the UK Biobank and other independent European and non-European cohorts.</p><p><strong>Methods and findings: </strong>We performed mGWAS using 516 lipid metabolites in 3,000 Punjabi Sikh individuals, and validation was performed in 1.13M Europeans and 15K individuals from Asian Indian ancestry using independent cohorts of the UK Biobank, GeneRISK, DIAMANT, PROMIS, and other studies. We identified 609 SNP-metabolite associations representing 236 SNP-metabolite pairs that attained genome-wide significance (p </= 5 × 10-8). Of the 36 SNP-lipid metabolite signals that survived multiple testing correction (p </= 1.92 × 10-10), 33 associations were not reported before, and 3 associations were confirmed to be ancestry-specific. Using colocalization analysis, polygenic risk scores, and Mendelian randomization approaches, we identified a causal association of LPC O-16:0 with T2D, represented by a lead variant in CD45, a key regulator of T- and B-cell antigen receptor signaling, and is already used as a therapeutic target. Another possible causal relationship of PC 38:4 (C) in protecting against coronary artery disease risk in Asian Indians, attributed to a variant in the untranslated region in the FADS1/2 genes, may be specific to ancestry and/or could not be confirmed in Europeans because of extensive pleiotropy in this region. The main limitation of this study was the absence of an independent validation cohort of Asian Indians from India.</p><p><strong>Conclusions: </strong>The mGWAS of Asian Indians offers new insights into the diverse molecular origins of cardiometabolic diseases and suggests potential pathways for innovative treatments. Our findings highlight the need for additional research on human lipidomics to better understand the downstream effects of the genome and its impact on cardiometabolic health.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"23 4","pages":"e1005039"},"PeriodicalIF":9.9,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786843","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}

{"title":"Quality of antenatal and delivery care and postnatal care use: A multi-country observational study of 400,000 births.","authors":"Jan E Cooper, Hwa-Young Lee, Katherine Wright, Prashant Jaryan, Margaret E Kruk","doi":"10.1371/journal.pmed.1005055","DOIUrl":"https://doi.org/10.1371/journal.pmed.1005055","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Postnatal care (PNC) plays a crucial role in averting newborn mortality, yet its use remains low, particularly in regions with the highest mortality. While demographic and social determinants of PNC use have been well studied and have informed current strategies focused on changing care-seeking behaviors, the stagnating decline in neonatal mortality highlights the need for upstream and system-wide approaches to increase PNC uptake. Limited evidence exists to guide system-level reforms; therefore, we investigated whether health systems that ensure high-quality perinatal care are associated with increased use of PNC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;We performed a cross-sectional observational study using Demographic and Health Survey data from 38 countries that had not met SDG neonatal mortality targets by 2020. The study population comprised women aged 15-49 years whose most recent live birth occurred within five years preceding the survey. We employed logistic regression models with country fixed effects to examine associations between: (1) perinatal service utilization, (2) service quality; and their relationship with postnatal checkups for newborns within 28 days. We analyzed utilization-quality interactions to determine how the effects of service coverage on PNC use varied by care quality and conducted wealth-stratified analyses to assess how quality effects on PNC use differed across socioeconomic groups. High-quality perinatal care was associated with a 2-fold increase in the probability of postnatal checkups within 28 days (0.406 in the highest quality tertile versus 0.221 in the lowest quality tertile). For mothers who received the lowest tertile of service quality, full utilization of perinatal services yielded negligible changes in postnatal checkup probability (0.217 to 0.216). Conversely, for mothers who received the highest quality of antenatal and perinatal care, full access to perinatal care improved the probability of postnatal check-ups (0.392 to 0.428). Notably, women in the lowest wealth quintile experienced a substantial increase in postnatal checkup probability from 0.224 to 0.481 between low and high-quality care cohorts, while this differential was less pronounced in the highest wealth quintile (0.236 to 0.450). Key limitations include restricted quality indicators, potential recall bias from self-reported measures, limited information on follow-up care, and the cross-sectional nature of the data, which limits causal interpretation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Our interaction analysis reveals a critical insight: high-quality care substantially enhanced the magnitude of the association between expanded perinatal service use and PNC use, whereas increased utilization alone was not linked to higher PNC uptake. Notably, the impact of improved care quality was most pronounced among the lowest wealth groups, highlighting its potential as a mechanism for promoting equity. By demo","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"23 4","pages":"e1005055"},"PeriodicalIF":9.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786822","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}

{"title":"Association between gabapentinoid treatment, concurrent use with opioid or benzodiazepine and the risk of drug poisoning: A self-controlled case series study.","authors":"Andrew S C Yuen, Boqing Chen, Adrienne Y L Chan, Joseph F Hayes, David P J Osborn, Frank M C Besag, Wallis C Y Lau, Ian C K Wong, Li Wei, Kenneth K C Man","doi":"10.1371/journal.pmed.1005035","DOIUrl":"10.1371/journal.pmed.1005035","url":null,"abstract":"<p><strong>Background: </strong>Consumption of gabapentinoids has increased worldwide in recent years, and the association between its use and drug poisoning is of public health concern. This study aimed to investigate the association between gabapentinoid treatment and the risk of drug poisoning.</p><p><strong>Methods and findings: </strong>In this within-individual study, we utilised data from the United Kingdom (UK) Clinical Practice Research Datalink (CPRD) Aurum database linked to the Hospital Episode Statistics (HES) and Office for National Statistics (ONS). The analysis included individuals aged 18 or above who were prescribed gabapentinoids and had an incident all-cause drug poisoning event between 1st January 2010 and 31st December 2020. Using the self-controlled case series (SCCS) design, we assessed the risk of drug poisoning incidence in predefined risk periods: 90 days before treatment initiation, first 28, 29-56, 57-84 days, and the remaining treatment time. Concomitant use with opioids/benzodiazepines was also evaluated. Adjusted incidence rate ratios (aIRRs) were calculated using conditional Poisson regression. A case-case-time-control (CCTC) analysis was also conducted, with adjusted odds ratio (aOR) calculated to validate the findings from the main SCCS analysis. All analyses have adjusted for key time-varying confounders, including age, season, and concomitant use of opioids, antiseizure medications, psychotropic medications, and non-steroidal anti-inflammatory drugs (NSAIDs). 16,827 individuals met the inclusion criteria and were included in the SCCS analysis. The risk of drug poisoning, compared with the reference periods, increased during the first 28 days of gabapentinoid treatment (aIRR = 1.81, 95% confidence interval [CI] [1.66, 1.99]; p < 0.001), eventually dropped to 1.11 (95% CI [1.05, 1.17]; p < 0.001) in the remainder of the treatment period. Notably, the risk was doubled during the 90-day preceding treatment initiation (aIRR = 2.09, 95% CI [1.98, 2.21]; p < 0.001). Co-administration with opioids elevated the risk by 30%, while benzodiazepines increased it 2-fold. The CCTC analysis also detected an increased aOR of 1.36 (95% CI [1.12, 1.65]; p = 0.002) of receiving gabapentinoid treatment within 30 days prior to a drug poisoning event. The SCCS approach cannot completely exclude the effect of unmeasured time-varying confounders, such as transient changes in socioeconomic status, major life events, or illicit drug use, although the negative control analysis did not suggest meaningful residual confounding.</p><p><strong>Conclusions: </strong>The results suggest that gabapentinoid is associated with an increased risk of drug poisoning. Close monitoring throughout gabapentinoid treatment journey for drug poisoning is needed, especially at the initial phase. Concomitant use with opioid or benzodiazepines should be avoided.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"23 4","pages":"e1005035"},"PeriodicalIF":9.9,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13086301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147700454","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}