Pharmacoepidemiology and Drug Safety最新文献

{"title":"Methylphenidate and Long-Term Risk of Cardiovascular Diseases: A Nationwide Cohort Study.","authors":"Christelle Berthod, Thomas Loppinet, Marietou Ndiaye, Inesse Boussaha, Matthias Jacquet-Lagreze, Behrouz Kassaï-Koupai","doi":"10.1002/pds.70493","DOIUrl":"10.1002/pds.70493","url":null,"abstract":"<p><strong>Purpose: </strong>Cardiovascular safety of methylphenidate remains a matter of debate.</p><p><strong>Methods: </strong>To evaluate the long-term cardiovascular risk associated with methylphenidate use, a cohort study was conducted using the French National Health Data System. New users were defined by a first methylphenidate dispensation (index date) between January 1, 2014, and December 31, 2023. Each new user was matched with three nonusers by sex and by month and year of birth. Individuals with prior cardiovascular disease or relevant cardiovascular comorbidities were excluded. The primary outcome was cardiovascular disease, defined by International Classification of Diseases codes or antihypertensive drug use. Cox proportional hazards models estimated adjusted hazard ratios (HRs), accounting for demographic and clinical covariates. Negative control outcomes were used to assess residual confounding, allowing the derivation of calibrated HRs and confidence intervals.</p><p><strong>Results: </strong>A total of 212 216 new users and 636 648 matching nonusers were included. Mean age was 13.7 years and 72% were males. Over a follow-up of ~4 years, 3858 cardiovascular diseases occurred (0.45%): 1960 in new users (9.2 per 1000) and 1898 in nonusers (3 per 1000). The adjusted HR was 2.37 (95% CI [2.21; 2.54]), with a calibrated HR of 1.85 (95% CI [1.55; 2.21]).</p><p><strong>Conclusions: </strong>The results suggest that methylphenidate use may be associated with an increased risk of cardiovascular diseases. Although the calibrated estimates indicate attenuation due to residual confounding, the association remained statistically significant. This supports recommendations for cardiovascular monitoring during treatment.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 10","pages":"e70493"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168701","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":"Reported Dosing-Related Medication Errors Involving Systemic Antibiotics in the Brazilian Pharmacovigilance Database (2018-2025): Distribution Across the WHO AWaRe Classification.","authors":"Valcieny Sandes, Alice Ramos-Silva, Adriana Ivama-Brummell, Albert Figueras, Elisangela Costa Lima","doi":"10.1002/pds.70496","DOIUrl":"10.1002/pds.70496","url":null,"abstract":"<p><strong>Purpose: </strong>Appropriate antibiotic dosing is essential to minimise treatment failure and reduce selective pressure that may contribute to antimicrobial resistance. This study characterised antibiotic medication-error drug-event pairs (MEPs) reported to the medicines Individual Case Safety Reporting (ICSR) system, VigiMed and assessed the distribution of dosing-related error drug-event pairs (DEPs) across World Health Organization (WHO) AWaRe (Access, Watch, and Reserve) antibiotic classes.</p><p><strong>Methods: </strong>We conducted an exploratory cross-sectional analysis of reports involving systemic antibiotics (Anatomical Therapeutic Chemical, ATC Classification System as J01 - antibacterials for systemic use) from Brazil's open-access pharmacovigilance database (VigiMed) from 2018 to 2025. MEPs were identified using the Standardised MedDRA Query for Medication Error; within this group, Preferred Terms (PTs) related to dose amount, timing, frequency, duration, or rate of administration were classified as DEPs (32 PTs). Descriptive analyses and modified Poisson regression were used to examine demographic and reporting characteristics associated with MEP classification and, among MEPs, the association between AWaRe class and DEP classification.</p><p><strong>Results: </strong>The adjusted prevalence of MEP classification was higher among neonates (PR 3.90), infants (PR 1.78) and older adults (PR 1.70) than among adults. DEPs accounted for 31.7% of MEPs (n = 2587; 61 antibiotics), with dose omission (51.4%) and dosing regimen problems (16.7%) as the leading error subtypes. Among DEPs, 35.9% involved Access, 56.7% Watch and 7.1% Reserve antibiotics. In adjusted analyses, Watch (PR 1.14; 95% CI 1.07-1.22) and Reserve (PR 1.31; 95% CI 1.16-1.49) antibiotics showed a higher prevalence of DEPs than Access antibiotics.</p><p><strong>Conclusions: </strong>This study analyses pharmacovigilance data on antibiotic dosing-related medication errors, highlighting potential opportunities for antimicrobial stewardship.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 10","pages":"e70496"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128431","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":"High Risk of Metabolic Side Effects Among New Paediatric Antipsychotic Users in Sweden-A Register-Based Study.","authors":"Elin Eyfells Kimland, Anders Sundström, Sverre Wikström, Håkan Jarbin, Elin Dahlén","doi":"10.1002/pds.70482","DOIUrl":"10.1002/pds.70482","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to assess the risk of metabolic side effects among paediatric new users of antipsychotics in Sweden, focusing on differences between substances and sexes.</p><p><strong>Methods: </strong>Children aged 5-17 years, who were new users of antipsychotics between 2014 and 2021, were identified using Swedish national health registers. Cox' models were fitted for children during first treatment with an antipsychotic, excluding those with eating disorders, yielding hazard ratios (HRs) for metabolic side effects with 95% confidence intervals (CIs).</p><p><strong>Results: </strong>A total of 5441 children were new users of antipsychotics. Of these, 399 (7.3%; 42% girls) received a new diagnosis or new treatment indicating a metabolic side effect, of which 139 cases during first-line treatment and without an eating disorder diagnosis. Obesity was the most common metabolic side effect, accounting for 69% of the cases. In girls, significantly increased risks were observed for aripiprazole (HR 3.52, 95% CI 1.58-7.80), olanzapine (HR 6.99, 95% CI 2.34-20.93) and quetiapine (HR 4.87, 95% CI 1.97-12.04), compared with risperidone. Younger girls had higher risks. In boys, a significantly increased risk was found for aripiprazole (HR 2.21, 95% CI 1.37-3.56).</p><p><strong>Conclusion: </strong>The overall risk of metabolic side effects is considerable, with higher relative risks in girls, especially younger girls. These findings highlight the need for carefully considered treatment and attentive monitoring when initiating antipsychotics in children.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 10","pages":"e70482"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017516","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":"Validation of Claims-Based Algorithms for Intussusception Identification in Japanese Hospitals: A Multicenter Analysis From the CLEAR Study.","authors":"Kumiko Saito, Chieko Ishiguro, Kazuki Sato, Masahiro Nakatochi, Haruhisa Fukuda","doi":"10.1002/pds.70488","DOIUrl":"10.1002/pds.70488","url":null,"abstract":"<p><strong>Purpose: </strong>Intussusception is a serious condition and a rare adverse event of rotavirus vaccination. While health insurance claims data are increasingly used for epidemiological research, claims-based algorithms for identifying intussusception have not been validated in Japan. This study aimed to validate multiple claims-based algorithms for intussusception identification against ultrasound findings as the reference standard.</p><p><strong>Methods: </strong>This validation study used claims data and ultrasound findings from three Japanese hospitals between 2011 and 2024. The study population comprised all patients who received care during each hospital's data period. We developed 10 algorithms combining an intussusception diagnostic code (ICD-10: K56.1), hospitalization status, ultrasound imaging codes, and surgery codes. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each algorithm. Age- and sex-stratified analyses were also performed.</p><p><strong>Results: </strong>Among 701 263 patients (mean age: 41.8 years; 52.0% female), 79 true intussusception cases (mean age: 8.3 years; 41.8% female) were identified (prevalence: 0.0113%). While sensitivity (54.4%-77.2%) and PPV (8.9%-28.1%) varied according to definition stringency, all algorithms achieved near-perfect specificity and NPV (≥ 99.9%). The algorithm that only used the diagnostic code yielded the highest sensitivity, while the algorithm that incorporated all four criteria achieved the highest PPV. Algorithm validity varied by age, with higher sensitivity and PPV for children aged ≤ 5 years.</p><p><strong>Conclusion: </strong>The algorithms demonstrated a trade-off between sensitivity and PPV, and researchers should select algorithms according to their study objectives. Our findings provide a robust foundation to guide algorithm selection for intussusception research using Japanese claims data.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 10","pages":"e70488"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075353","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":"Applying a Pareto-Based Efficiency Frontier to Inform Value-Based Pricing for Gaucher Disease Therapies in Brazil.","authors":"Marcus Carvalho Borin, Ludmila Peres Gargano, Francisco de Assis Acurcio, Juliana Álvares-Teodoro, Augusto Afonso Guerra","doi":"10.1002/pds.70497","DOIUrl":"10.1002/pds.70497","url":null,"abstract":"<p><strong>Purpose: </strong>Gaucher disease (GD) requires lifelong high-cost treatment within the Brazilian Unified Health System (SUS). In Brazil, treatment eligibility and monitoring are defined by Clinical Protocol and Therapeutic Guidelines (PCDT), while pharmaceutical prices are regulated by the Drug Market Regulation Chamber (CMED). Exploratory price-value approaches may help make explicit the relationship between drug prices and measurable clinical benefit. We explored the applicability of a Pareto-based Efficiency Frontier (EF) as a descriptive hematologic price-value framework for GD therapies in Brazil.</p><p><strong>Methods: </strong>An exploratory Pareto-based EF analysis compared annual drug acquisition prices with standardized hematologic benefits, defined as hemoglobin and platelet improvements, derived from a published systematic review. Annual prices were obtained from CMED, Maximum Price of Sale to the Government (PMVG), and median public procurement prices from the Health Price Database (BPS). Prices are presented in Brazilian reais and USD adjusted by purchasing power parity. Directly dominated technologies were excluded, and all remaining directly non-dominated therapies were connected by linear interpolation to form a Pareto-based 12-month reference EF. This construction retains alternatives that would be excluded by extended dominance under a conventional convex EF. The analysis was restricted to treatment-naïve patients.</p><p><strong>Results: </strong>Annual costs ranged from approximately USD-PPP 94900 to 763 200. Under the primary 12-month analysis, imiglucerase was directly dominated across all three pricing scenarios, whereas taliglucerase alfa, velaglucerase alfa, and miglustat defined the Pareto-based frontier. In the BPS hemoglobin analysis and in all three platelet analyses, taliglucerase alfa would be subject to extended dominance under a conventional convex EF but was retained as a directly non-dominated therapy. This classification was conditional on indirect comparisons from heterogeneous evidence and the selected 12-month hematologic point estimates. In the descriptive scenario analysis, direct dominance of imiglucerase was less stable when maximum effects across longer follow-up durations were considered.</p><p><strong>Conclusion: </strong>This exploratory application of a Pareto-based Efficiency Frontier describes the relationship between current price scenarios and comparative hematologic benefit for GD therapies. Findings should not be interpreted as definitive comparative value evidence, an ICER-based optimization rule, or a stand-alone pricing instrument. The approach may complement broader value-based assessment alongside QALY-based modeling, long-term outcomes, formal uncertainty analysis, and non-hematologic clinical dimensions.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 10","pages":"e70497"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148748","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":"Letter to the Editor.","authors":"Byeong Yeob Choi","doi":"10.1002/pds.70500","DOIUrl":"10.1002/pds.70500","url":null,"abstract":"","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 10","pages":"e70500"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Active and Non-Active Comparators Yield Different Estimates of the Association Between Proton Pump Inhibitor Use and Recorded Mortality During Immune Checkpoint Inhibitor Therapy for Advanced Non-Small Cell Lung Cancer.","authors":"Yasutaka Ihara, Naoto Okada, Megumi Mizutani, Yukihiro Nakamura, Yuki Shimomura, Shoichiro Yamamoto","doi":"10.1002/pds.70478","DOIUrl":"10.1002/pds.70478","url":null,"abstract":"<p><strong>Purpose: </strong>Proton pump inhibitor (PPI) use has been associated with poorer outcomes in patients receiving immune checkpoint inhibitors (ICIs), but most previous studies have compared PPI users with non-users, which may differ in their underlying need for acid-suppressive therapy. We evaluated the association between PPI use and mortality using histamine-2 receptor antagonist (H2RA) users as an active comparator among patients with advanced non-small cell lung cancer (NSCLC) receiving ICIs.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study using a Japanese administrative claims database. Patients with advanced NSCLC who initiated first-line ICI-based therapy and received either a PPI or an H2RA within 30 days before or on the day of ICI initiation were included. The index date was defined as the initiation date of the first-line ICI-based regimen. The primary outcome was all-cause mortality within 3 years. Propensity score overlap weighting was used to balance baseline characteristics, and weighted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).</p><p><strong>Results: </strong>Among 6360 eligible patients, 5409 received conventional PPIs and 951 received H2RAs. After overlap weighting, mortality did not clearly differ between PPI and H2RA users (HR, 1.06; 95% CI, 0.93-1.20). In contrast, PPI users had higher mortality than patients receiving neither PPIs nor H2RAs (HR, 1.13; 95% CI, 1.05-1.20).</p><p><strong>Conclusion: </strong>PPI use was not clearly associated with higher mortality when H2RA users were used as an active comparator, whereas a higher mortality estimate was observed when PPI users were compared with patients receiving neither PPI nor H2RA therapy. These findings highlight the importance of comparator selection in observational studies evaluating PPI use during ICI therapy.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 9","pages":"e70478"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13574716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148970685","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 Catalogue of Dispensation Lengths for Building Treatment Episodes-Application of the Waiting Time Distribution to All Commonly Prescribed Drugs in Denmark.","authors":"Mette Reilev, Lotte Rasmussen, Jonas Kanstrup Olsen, Martin Thomsen Ernst, Saad Hanif Abbasi, Rikke Wesselhoeft, Mette Bliddal, Jesper Hallas, Henrik Støvring","doi":"10.1002/pds.70443","DOIUrl":"10.1002/pds.70443","url":null,"abstract":"<p><strong>Background: </strong>In pharmacoepidemiologic research, correct assignment of the length of single dispensation is critical to build treatment episodes. The parametric reverse waiting time distribution (rWTD) is a particularly attractive data-driven method to estimate dispensation lengths.</p><p><strong>Aim: </strong>To provide an easily accessible resource of estimated dispensation lengths covering all commonly used drugs for use in treatment episode building in applied pharmacoepidemiologic research.</p><p><strong>Methods: </strong>We used a random 20% sample of the Danish population alive after 1st January 2000 and identified all their prescriptions filled between 2010 and 2022. We applied the rWTD with five random index dates for each individual to estimate parameters that allow calculation of dispensation length estimates. Parameters were estimated with and without age, sex, and dispensed amount as covariates.</p><p><strong>Results: </strong>We present estimated dispensation lengths for the 20 most prescribed drugs and drug classes in Denmark. Estimated dispensation lengths for all drugs are provided online, and in a spreadsheet. The most prescribed drug was paracetamol with an estimated dispensation length of 194 days, while atorvastatin was the most commonly used drug indicated for long-term use with an estimated dispensation length of 165 days. The dispensation lengths for drugs varied according to age, dispensed volume, sex, and over time.</p><p><strong>Conclusions: </strong>This is a comprehensive overview of dispensation lengths for all commonly prescribed drugs registered in the Danish National Prescription Registry. Data presented in an online resource can be utilized and modified by other researchers providing optimal conditions for high quality pharmacoepidemiologic research.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 9","pages":"e70443"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13498435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796357","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":"Temporal Changes in Dispensing of Methylphenidate During Attention Deficit Hyperactivity Disorder Shortages in Australia: An Interrupted Time Series and Descriptive Analysis of National Dispensing Patterns.","authors":"George Gadalla, Wern Chai, Lisa Kalisch Ellett, Jack Janetzki","doi":"10.1002/pds.70475","DOIUrl":"10.1002/pds.70475","url":null,"abstract":"<p><strong>Purpose: </strong>To describe nationwide dispensing patterns of methylphenidate in Australia before and during recent prolonged supply shortages, and to assess the extent to which Section 19A (S19A) overseas substitutes contributed to population-level utilisation during the shortage period. Secondary aims were to compare methylphenidate dispensing with other ADHD medicines, examine changes in dispensing across individual strengths and formulations and quantify delays between S19A approval and Pharmaceutical Benefits Scheme (PBS) listing.</p><p><strong>Methods: </strong>An interrupted time series (ITS) and descriptive analysis of population-level dispensing patterns was conducted using publicly available monthly dispensing data from the Pharmaceutical Benefits Scheme (PBS) and Repatriation PBS (January 2020-March 2026). Data were standardised to dispensings and defined daily doses (DDD) per 100 000 population. Methylphenidate shortages were identified using the Therapeutic Goods Administration Medicines Shortages database and shortage months were designated where there was at least 1 day of shortage in a month. S19A approvals, PBS listing and lapse dates were obtained from the S19A approvals database to determine delays to subsidised access.</p><p><strong>Results: </strong>Dispensing of ADHD medicines increased substantially from 2020 to 2025. Methylphenidate dispensing increased overall but plateaued from late 2024 onward, coinciding with widespread supply disruptions affecting multiple strengths and formulations. DDD ITS analysis demonstrated abrupt reductions in methylphenidate strengths (particularly 36 and 54 mg) during shortages, with partial compensatory increases for some other strengths. Fifteen overseas-registered methylphenidate products received S19A approval; however, of the 14 listed on the PBS, time to PBS listing ranged from 83 to 166 days (median 162 days). After PBS listing, S19A products contributed to 1.3% of all methylphenidate dispensings between July 2025 and March 2026.</p><p><strong>Conclusion: </strong>Methylphenidate dispensing in Australia became unstable during extensive supply shortages from late 2024. Although numerous S19A products were approved, there was minimal uptake of S19A PBS-listed products at the population level. As ADHD medicine utilisation continues to rise, strengthened national strategies to improve supply chain resilience, transparency and responsiveness are required.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 9","pages":"e70475"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906626","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":"Endothelial and Vascular Toxicity Signals Associated With Doxorubicin: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System (FAERS) Database.","authors":"Emelith Florendo Cerbito, Lana Kattan, Hevna Dhulkifle, Hesham M Korashy, Zaid H Maayah","doi":"10.1002/pds.70474","DOIUrl":"10.1002/pds.70474","url":null,"abstract":"<p><strong>Purpose: </strong>Doxorubicin (DOX), an effective anticancer agent, is associated with dose-dependent cardiovascular toxicity. Understanding its mechanisms and risk factors will facilitate novel interventions to minimize DOX-induced cardiovascular toxicity. Thus, this study performed data mining of the FDA Adverse Event Reporting System (FAERS) to detect and analyze DOX-induced cardiac-related adverse events (AEs).</p><p><strong>Methods: </strong>Data from 2004 to 2025, where DOX was the primary suspect, were extracted from FAERS via OpenVigil. Using the Medical Dictionary for Regulatory Activities, AEs were categorized into preferred terms (PTs) and system organ classes (SOCs). This study used descriptive analysis and signal detection algorithms including Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), Multi-item Gamma Poisson Shrinker (MGPS), and Bayesian Confidence Propagation Neural Network (BCPNN).</p><p><strong>Results: </strong>A total of 2421 reports of DOX-associated AEs were extracted in FAERS. Reports primarily involved female cancer patients (55.02%) between 18and 65 years (48.12%) from the United States. Most signals were of moderate to strong signal intensity, with cardiotoxicity, cardiac failure, and cardiomyopathy being the most reported. Interestingly, while cardiac disorders were mainly found to be strongly linked to DOX, novel vascular AEs like endothelial dysfunction were also among the top signals strongly associated with DOX. Out of the six serious AEs associated with DOX-induced cardiotoxicities, \"Death\" and \"Initial/prolonged hospitalization\" were the most commonly reported.</p><p><strong>Conclusion: </strong>This study provides valuable insights into DOX-induced cardiovascular toxicity using real-world data from FAERS. Vascular events like endothelial dysfunction were shown to be significant novel AEs experienced by cancer patients undergoing treatment with DOX. Thus, careful monitoring of potential DOX-AEs associations will help improve the risk-benefit ratio of DOX-treated patients.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 9","pages":"e70474"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13549743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906670","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}