Pharmacoepidemiology and Drug Safety最新文献

{"title":"Prenatal Exposure to Modafinil and the Risk of Major Congenital Anomalies and Other Adverse Neonatal and Pediatric Outcomes.","authors":"Melinda Kanoun, Naïm Bouazza, Jean-Marc Treluyer, Mathis Collier","doi":"10.1002/pds.70448","DOIUrl":"10.1002/pds.70448","url":null,"abstract":"<p><strong>Objective: </strong>To assess the risk of major congenital anomalies (MCAs) and other adverse outcomes following prenatal exposure to modafinil.</p><p><strong>Methods: </strong>This retrospective cohort study used the French national healthcare database (SNDS) to include singleton children born between January 2009 and September 2024 of women aged 15-55 years. Prenatal exposure to psychostimulants was defined as maternal dispensation during pregnancy. Children prenatally exposed to modafinil were compared with two control groups: children prenatally exposed to methylphenidate and children prenatally unexposed to any psychostimulant matched to the exposed group using propensity-score matching (PSM). Outcomes included MCAs, neurodevelopmental disorders (NDs), and specialized consultations. Analyses included descriptive statistics, survival analysis, regression models, and dose-response analyses.</p><p><strong>Results: </strong>Of 10 955 766 included children, 865 were prenatally exposed to modafinil and 950 to methylphenidate. Exposure to modafinil during the first trimester of pregnancy was statistically associated with increased risk of MCA compared to methylphenidate, although the confidence interval was wide and close to the null (aRR = 1.77 [1.01-3.07]). Comparison with PS-matched unexposed population indicated a possible modest increase in risk, albeit with a wide confidence interval crossing the null (aRR = 1.23 [0.76-1.99]), showing no clear association. Occurrence of NDs (aHR = 0.96 [0.56-1.65]), and specialized consultations (aHR = 1.08 [0.91-1.28]) were similar in the modafinil and PSM unexposed groups but were higher in the methylphenidate group (NDs: aHR = 0.48 [0.29-0.80]; specialized consultations: aHR = 0.71 [0.59-0.85]).</p><p><strong>Conclusion: </strong>This study shows no increase in neurodevelopmental risk, while a moderate MCA risk cannot be excluded.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 8","pages":"e70448"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148664307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological Therapy in Patients With Gender Dysphoria: A Cohort Study in the Lazio Region, Italy.","authors":"Valeria Belleudi, Sara Lopes, Michela Servadio, Arianna Bellini, Antonio Addis","doi":"10.1002/pds.70445","DOIUrl":"10.1002/pds.70445","url":null,"abstract":"<p><strong>Purpose: </strong>Individuals with gender dysphoria (GD) experience discomfort or distress related to gender incongruence. Management often requires pharmacological support for hormonal and psychological needs. This study aimed to identify a cohort of GD patients in the Lazio Region and analyze their medication use compared with the general population.</p><p><strong>Methods: </strong>Using regional health information systems, we identified individuals with incident hospitalizations for GD between 2011 and 2021. We assessed medication use in the year following discharge and compared it with an age- and sex-matched population sample (1:10 ratio). We calculated the proportion of individuals with at least one dispensed prescription in selected therapeutic classes, with 95% confidence intervals.</p><p><strong>Results: </strong>We identified 365 individuals with GD (median age 26 years), of whom 52.9% were assigned male at birth (AMAB) and 47.1% were assigned female at birth (AFAB). Within one year, 72.1% (67.5%-76.7%) of GD individuals received at least one medication, compared to 43.1% (41.5%-44.7%) in the general population. Medicine use was higher among AMAB (83.9%) than AFAB (58.7%). The most prescribed drug classes were anti-infectives (35%), sex hormones (35%), gastrointestinal/metabolic agents (28%), and nervous system drugs (18%). Patterns differed by sex assigned at birth: estrogens, anti-androgens, and vitamins were common in AMAB, while acid-related disorder drugs, psychotropics, and testosterone were more frequent in AFAB.</p><p><strong>Conclusions: </strong>GD patients showed higher medication use than the general population, with distinct patterns by sex assigned at birth. These findings highlight the importance of monitoring and evaluating long-term safety of pharmacological therapies.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 8","pages":"e70445"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13426041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148631098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on 'Comparative Effectiveness and Safety of Three Oral Antihypertensive Therapies on Maternal and Infant Outcomes in a California Medicaid Population, 2016-2020'.","authors":"Maajid Mohi Ud Din Malik, Rajesh Prasad Jayaswal","doi":"10.1002/pds.70444","DOIUrl":"10.1002/pds.70444","url":null,"abstract":"","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 8","pages":"e70444"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13406910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148606157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population-Based Trends in Antidepressant Dispensing Among Children and Adolescents in Manitoba, Canada.","authors":"Amani F Hamad, Kevin J Friesen, Yejin Cha, Cara Katz, Abdullah Maruf","doi":"10.1002/pds.70455","DOIUrl":"10.1002/pds.70455","url":null,"abstract":"<p><strong>Purpose: </strong>This study quantified temporal trends in antidepressant dispensing among children and adolescents and described patterns by antidepressant class, drug, and demographic subgroups.</p><p><strong>Methods: </strong>This population-based cohort study used administrative health data from Manitoba, Canada and included individuals aged 6-18 years between 2000 and 2024. Antidepressant dispensing was identified in prescription dispensing records using the Anatomical Therapeutic Chemical code N06A. Annual prevalence was defined as the proportion of individuals dispensed antidepressants in a given year; annual incidence rate was defined as the rate of new antidepressant dispensing following a 2-year washout period. Analyses were stratified by antidepressant class, drug, age group (6-12, 13-18), sex and neighborhood income quintiles.</p><p><strong>Results: </strong>The cohort included 699 526 individuals; 66 895 (9.6%) had an antidepressant dispensing, of which most were dispensed selective serotonin reuptake inhibitors (n = 49 219, 73.6%). The prevalence of antidepressant dispensing increased from 14.9 (95% confidence interval [CI] 14.5-15.5) to 48.7 (95% CI 47.9-49.6) per 1000 individuals in 2000 and 2024, respectively. The incidence increased from 9.2 (95% CI 8.8-9.6) to 17.4 (95% CI 16.8-17.9) per 1000 person-years. A decline in dispensing between 2003 and 2005, and a sharp rise beginning in 2020, were observed. Subgroup analyses showed a temporal increase in antidepressant dispensing across all subgroups, particularly among females and adolescents aged 13-18 years.</p><p><strong>Conclusions: </strong>This study found a marked increase in antidepressant dispensing in children and adolescents over time, particularly in females and adolescents. Future studies are needed to evaluate appropriateness, clinical outcomes and long-term safety of antidepressant use in this population.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 8","pages":"e70455"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13459037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Pharmaco-Epidemiological Research Program Leveraging a Nationwide Database of Kidney Transplantation.","authors":"Pierre Marquet, Antoine Humeau, Sabrina Crépin, Clément Benoist, Sylvain Couderc, Caroline Monchaud, Marc Labriffe, Franck Saint-Marcoux","doi":"10.1002/pds.70442","DOIUrl":"10.1002/pds.70442","url":null,"abstract":"<p><strong>Objectives: </strong>The pharmaco-epidemiological research program in kidney transplantation (PERP-KT) aims to evaluate, for the principal maintenance immunosuppressive drugs (MISDs): the influence of model-informed precision dosing on graft and patient survival; long-term exposure-effects relationships; and the benefit-harm balance of their combinations and time sequences in patient groups or clinical settings not adequately evaluated in comparative randomized clinical trials. It also aims to develop a hybrid, dynamic, deep learning model capable of predicting the rate of renal graft function decline, thereby providing a platform for individualized prediction of the benefits and risks associated with MISDs.</p><p><strong>Patients and methods: </strong>After obtaining all regulatory andd ethical approvals, de-identified extracts of three national databases were linked to create the nationwide PERP-KT dataset, which is hosted within the highly secure environment of the French Health Data Hub.</p><p><strong>Results: </strong>CRISTAL (the exhaustive registry of the French Agence de la Biomédecine) comprises data from 49 886 kidney donors and the corresponding 47 842 transplant recipients between 2005 and 2020. Following iterative deterministic matching and extensive quality control procedures, CRISTAL data were successfully linked to: the French national Health Data System (SNDS), which records reimbursed healthcare utilization, for 30 782 kidney transplant recipients; and to ISBA, a web-based platform for Bayesian dose adjustment of MISDs that contains pharmacological data, for 17 700 kidney grafts and 17 576 recipients.</p><p><strong>Perspectives: </strong>More than 20 pharmaco-epidemiological studies will leverage the database's extensive follow-up, large population size and richness of clinical, healtcare-utilization, and pharmacological data.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 8","pages":"e70442"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Active Safety Surveillance Using Real-World Evidence (ASSURE) Implementation: Transparent and Reproducible Real-World Evidence Standardized Framework to Support Safety Signal Evaluation.","authors":"Kevin Haynes, Jenna Reps, Jill Hardin, Eva-Maria Didden, James Gilbert, Joel Swerdel, Justin Bohn, Mitchell M Conover, Amir Sarayani, Anthony G Sena, Emily Yost, Valerie van Baalen, Kourtney Davis, Patrick Ryan, Martijn Schuemie","doi":"10.1002/pds.70435","DOIUrl":"10.1002/pds.70435","url":null,"abstract":"<p><strong>Purpose: </strong>To summarize experience with Johnson & Johnson's novel Active Safety Surveillance Using Real-world Evidence (ASSURE) program for producing efficient, transparent, applicable, and impactful RWE to support routine pharmacovigilance processes.</p><p><strong>Methods: </strong>ASSURE follows a stepwise framework that encompasses database diagnostics to assess fit-for-purpose real-world data (RWD) sources in the US, France, Germany, Australia, and Japan, phenotype development, query specification, and analytic implementation, objective study validity diagnostics, and standardized reporting. Licensed RWD sources are transformed into the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM), from which we generate evidence for safety signal evaluation questions using a suite of open-source analytic tools made publicly available through the OHDSI community. For each signal evaluation request involving a medication exposure and outcome(s), we conducted population characterization and population-level causal effects estimation. Target medication, comparator medication, and indication cohorts utilize predefined phenotypes, when available, for rapid analytics. We provide an evaluation of the initial implementation of this framework, including results from database diagnostics, phenotype development, and objective study validity diagnostics applied prior to unblinding evidence to prevent exposing biased estimates. We defined efficiency as the time from query to results and integration of results into safety decisions.</p><p><strong>Results: </strong>The initial 19 months of the ASSURE program supported 110 safety signal evaluations across 24 unique products that arose from 47 requests. 74 evaluations (67%) passed study diagnostics and yielded effect estimation results with 62 (54%) providing propensity-score adjusted comparative cohort method results and 40 (36%) providing self-controlled case series results. Many analyses failed one or more diagnostics, preventing the generation and unblinding of potentially biased results: database (7 evaluations), phenotype specification (3 evaluations), or the requisite objective study validity diagnostics (26 evaluations). These 26 evaluations (24%) all provided population characterizations of exposure, indication, and outcome, including incidence rates.</p><p><strong>Conclusions: </strong>The ASSURE framework and implementation process, in collaboration with safety management teams, enables rapid response to medical product safety signals under evaluation and produces actionable RWE that supports pharmacovigilance decision making within regulatory timeframes.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 8","pages":"e70435"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DU-Vigilance; Capturing Unsuspected Problems in Drug Utilization.","authors":"Jesper Hallas, Hanin Harbi, Thomas Delvin, Lotte Rasmussen","doi":"10.1002/pds.70423","DOIUrl":"10.1002/pds.70423","url":null,"abstract":"","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 8","pages":"e70423"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13419929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148621044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug-Drug Interaction Signals for Major Bleeding in Nursing Home Residents: High-Throughput Screening of Clopidogrel and Oral Anticoagulants.","authors":"Adam M D'Amico, Melissa R Riester, Charles E Leonard, Daniel A Harris, Lori A Daiello, Yu-Chia Sam Hsu, Douglas P Kiel, Meghan A Cupp, Kaleen N Hayes, Andrew R Zullo","doi":"10.1002/pds.70441","DOIUrl":"10.1002/pds.70441","url":null,"abstract":"<p><strong>Purpose: </strong>Nursing home (NH) residents are at high risk for major bleeding and are frequently exposed to complex medication regimens that may increase the likelihood of clinically important drug-drug interactions (DDIs). However, DDI evidence from community-dwelling populations may not generalize to NH residents, and real-world signals involving clopidogrel and oral anticoagulants remain incompletely characterized in this setting. We aimed to identify and interpret candidate DDI signals for major bleeding involving clopidogrel and oral anticoagulants among NH residents.</p><p><strong>Methods: </strong>Using linked Minimum Data Set assessments and Medicare fee-for-service claims (2013-2020), we conducted high-throughput, self-controlled case series (SCCS) screening analyses for four object drugs (clopidogrel, apixaban, rivaroxaban, and warfarin) paired with candidate precipitant medications. We estimated rate ratios (RRs) and 95% confidence intervals (CIs) comparing periods of concomitant use versus object drug use alone, applying semi-Bayes shrinkage to reduce false-positive signals. To aid interpretation, we incorporated two negative controls: a negative-control object drug (pravastatin) and a negative-control outcome (fall-related injury). A panel of experts evaluated signals for biological plausibility and potential bias.</p><p><strong>Results: </strong>After semi-Bayes adjustment, 5/40 clopidogrel, 1/29 apixaban, 2/15 rivaroxaban, and 6/22 warfarin signals remained significant, and none did for pravastatin. Signals were also observed for fall-related injury. Experts identified only clopidogrel/sertraline and warfarin with cephalexin, sulfamethoxazole-trimethoprim, and furosemide as biologically plausible signals.</p><p><strong>Conclusion: </strong>SCCS screening for DDIs in NH residents identified bleeding signals for clopidogrel and oral anticoagulants, but few were mechanistically coherent and fall-related injury signals suggested residual bias.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 8","pages":"e70441"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Data for Safety Studies: Challenges and Opportunities From the Italian Multiple Sclerosis and Related Disorders Register.","authors":"Marco Salivetto, Tommaso Guerra, Pasquale Paletta, Vito Lepore, Paola Mosconi, Pietro Iaffaldano, Michela Ponzio","doi":"10.1002/pds.70432","DOIUrl":"10.1002/pds.70432","url":null,"abstract":"<p><strong>Introduction: </strong>Information on the safety profile of disease-modifying therapies (DMTs) in multiple sclerosis (MS) is often lacking in routine clinical practice. Real-world data sources, such as patient registries, support pharmacovigilance to characterise safety signals, as recently recognised by regulatory agencies. In Italy, the \"Italian Multiple Sclerosis and Related Disorders Register\" (RISM) was officially launched in 2015 to collect demographic and clinical data from patients with MS.</p><p><strong>Purpose: </strong>To describe the main characteristics of RISM as a research platform supporting the safety evaluation of MS therapies.</p><p><strong>Methods: </strong>RISM enables the systematic characterisation of clinical events occurring in treated patients and, over the years, has implemented procedures to ensure high-quality data collection. A study cohort including subjects who initiated a DMT between 2016 and 2025 is analysed using descriptive statistics. Clinical events recorded during the study period are reported as absolute numbers and frequencies.</p><p><strong>Results: </strong>Between 2016 and 2025, a total of 24 259 subjects received at least one DMT, and 4419 of them (18.2%) experienced one or multiple clinical events. For descriptive purposes, the occurrence of infections and malignancies, which accounted for 29.4% and 3.7% of all the clinical events collected in RISM respectively, are reported and categorised.</p><p><strong>Conclusions: </strong>This article outlines the strengths and limitations of RISM in conducting safety studies and highlights the methodological and legal challenges associated with such platforms. Routinely collected healthcare data within RISM provide a comprehensive, patient-centred perspective for the long-term evaluation of DMT safety and can address relevant questions on drug policies and public health.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 8","pages":"e70432"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13420742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Hierarchical Risk Assessment Framework for Population-Specific Statin Safety Labelling.","authors":"Leo Tsui","doi":"10.1002/pds.70440","DOIUrl":"10.1002/pds.70440","url":null,"abstract":"","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 8","pages":"e70440"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}