Pharmacoepidemiology and Drug Safety最新文献

{"title":"A Plasmode Simulation-Based Bias Analysis for Residual Confounding by Unmeasured Variables Leveraging Information-Rich Subsets.","authors":"Rishi J Desai, Shirley V Wang, Haritha S Pillai, Mufaddal Mahesri, Bowen Gu, Joyce Lii, Sarah Dutcher, Chanelle Jones, Fatma M Shebl, Marie C Bradley, Wei Hua, Hana Lee, Gerald J Dal Pan, Sebastian Schneeweiss, Robert Ball","doi":"10.1002/pds.70383","DOIUrl":"10.1002/pds.70383","url":null,"abstract":"<p><strong>Aim: </strong>To develop a quantitative bias analysis approach based on realistic assumptions reflective of the complexities of healthcare data.</p><p><strong>Methods: </strong>We describe a 'plasmode' simulation-based bias analysis for residual confounding from unmeasured variables by leveraging granular information from a subset of cohort members. We generated 500 simulated cohorts based on individual-level claims and linked electronic health record (EHR) data identifying new users of varenicline and bupropion from the Mass General Brigham site of the FDA Sentinel Real World Evidence Data Enterprise. Two adverse outcomes were simulated: (1) neuropsychiatric hospitalizations and (2) major adverse cardiovascular events (MACE), and measured confounding factors, identified from information available in claims including demographics, comorbid conditions, and comedications, were tailored to each outcome. Residual confounding was simulated using potential confounders measured in EHRs but unmeasured in claims including suicidal ideation for the neuropsychiatric outcomes and body mass index (BMI), blood pressure (BP), and smoking pack-years for the MACE outcome. These simulations retained the correlation between claims and EHR-based confounders observed in empirical data for realistic reflection of proxy adjustment of unmeasured confounders. Analyses were conducted in simulated data with and without adjustment for the EHR-based covariates to evaluate the extent of residual confounding in claims-only analyses.</p><p><strong>Results: </strong>After 500 simulations, the median absolute standardized mean difference (ASMD) between treatment groups in the unadjusted sample was 0.16 for suicidal ideation; while < 0.1 for BMI, BP, and smoking pack-years. For both outcomes, adjustment using claims-based variables provided relative bias close to 0, leading to the conclusion that EHR-measured confounders that were unmeasured in claims were unlikely to result in strong residual confounding within realistic simulations informed by empirical data.</p><p><strong>Conclusion: </strong>The proposed approach provides a method for quantifying bias in non-randomized studies threatened by the unavailability of potentially important confounding variables.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 5","pages":"e70383"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841294","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":"Methodological Characteristics in Economic Evaluations of Health Technology Assessment Reports Submitted for Drug Reimbursement in Brazilian Public Health.","authors":"Gilson Pires Dorneles, Cintia Pereira de Araujo, Suena Parahiba, Bruna Marmett, Ana Paula Blankenheim, Marina Guahnon, Cinara Stein, Maicon Falavigna","doi":"10.1002/pds.70371","DOIUrl":"https://doi.org/10.1002/pds.70371","url":null,"abstract":"<p><strong>Objectives: </strong>To characterize methodological aspects and the quality reporting of economic evaluation in HTA reports of drugs submitted to the Brazilian public health system.</p><p><strong>Methods: </strong>An electronic search for HTA reports focusing on drug incorporation into the public health system published between 2020 and June 2024 was conducted in the Conitec database. The study selection and data extraction were performed to obtain bibliographic data, base case characteristics, and methodological features. Furthermore, the quality reporting of economic evaluation was verified by the Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022). Descriptive statistics summarize the data extracted from the documents.</p><p><strong>Results: </strong>We included 188 economic evaluations of HTA reports about drug reimbursement; the great majority submitted to private companies or public institutions. Most economic evaluations adopted cost-utility or cost-effectiveness analysis using a comparator in the public system. Economic evaluation studies presented frequent inconsistent reports of cost and health outcomes and in the deterministic and probabilistic sensitivity analyses. Markov, decision tree, and partitioned survival model were the main mathematical models applied. Cost-effectiveness analysis mainly adopted QALY or QALY plus life-years gained as health outcomes, but there was a lack of clarity in the methods to incorporate health utilities in the cost-utility analysis. Finally, we identified that the quality reporting of economic evaluation needs to be improved.</p><p><strong>Conclusion: </strong>The methods and reporting quality of economic evaluations submitted to Conitec exhibit heterogeneity characteristics. Strengthening and standardizing guidance for preparing health economic evaluations is needed to ensure greater consistency, transparency, and decision-making reliability.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 5","pages":"e70371"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819271","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":"Identifying the Initiation of a New Line of Therapy for Metastatic Lung, Breast, and Colorectal Cancer in Real-World Data: A Scoping Review.","authors":"Oluwadamilola Onasanya, Seyed Hamidreza Mahmoudpour, Benjamin Bates, Irene M Shui, Geoffrey Liu, Eng Hooi Tan, Yi-Hsin Yang, Maribel Salas, Joseph Fadare, Dimitri Bennett, Paula Lana de M Drummond, Judy Ju-Young Shin, Sonia Guleria, Jocelyn R Wang, Manila Hada, Helene Denis, Soko Setoguchi, Ilse Truter, Luciane C Lopes, Ruth Wangia Dixon","doi":"10.1002/pds.70370","DOIUrl":"https://doi.org/10.1002/pds.70370","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to identify and synthesize published algorithms for identifying the initiation of a new line of therapy (LOT) for metastatic lung, breast, and colorectal cancer in real-world data (RWD).</p><p><strong>Methods: </strong>We conducted a scoping review of published, English-language studies describing algorithms for identifying any LOTs with systemic anti-cancer therapy (SACT) for either non-metastatic or metastatic lung, breast, or colorectal cancer in RWD between January 1, 2014, and April 29, 2024. Dual reviewers independently screened titles, abstracts, and full-text articles, with disagreements resolved by a third reviewer. Data were extracted, categorized, synthesized, and summarized in narrative and tabular formats.</p><p><strong>Results: </strong>The review identified 25 studies, mainly (64%) from the United States. Electronic health/medical records (EHRs) were the most frequently utilized (72%) RWD source. Twenty-four studies (96%) described RWD algorithms for identifying the initiation of a new LOT for metastatic lung, breast, or colorectal cancer. In 23 studies, algorithms required observing a new, adjuvant, SACT after an \"incident\" metastatic diagnosis code, which had been preceded by a metastasis-free lookback period of varied duration. Three studies' algorithms required observation of the completion of non-metastatic LOTs before initiation of a new LOT for metastatic cancer. Three studies validated their algorithms.</p><p><strong>Conclusions: </strong>Different algorithms are being used to identify LOT initiation for metastatic cancer. Most algorithms require an incident diagnosis of metastasis before considering subsequent SACT as newly initiated LOT for metastatic cancer. However, definitions of metastasis onset and gap duration to therapy initiation vary.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 5","pages":"e70370"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147778008","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":"Time Windows Used When Identifying Current Drug Use and Polypharmacy.","authors":"Sabrina Giometto, Mette Reilev, Martin Thomsen Ernst, Henrik Støvring, Anton Pottegård","doi":"10.1002/pds.70384","DOIUrl":"https://doi.org/10.1002/pds.70384","url":null,"abstract":"<p><strong>Purpose: </strong>The length of the time window used to assess \"current drug use\" or \"number of medications used\" will influence the estimates hereof; however, no consensus exists on the optimal width of such time windows. We aimed to explore how the estimated prevalence of drug use in general, and of polypharmacy in particular, is affected by definitions used.</p><p><strong>Methods: </strong>We conducted a drug-utilization study divided into two parts. In the first part, we focused on current drug use. Using population-based registries from Denmark, we identified adults (i.e., individuals aged ≥ 18) during 2020-2022, and among them, current use of different drugs, including those with typically chronic or episodic patterns of use. The second part of the study focused on polypharmacy. We estimated its prevalence, based on different definitions, using population-based registries from Denmark in a cohort of older adults (i.e., individuals aged ≥ 65) in 2022. We also evaluated the accuracy of different criteria for predicting polypharmacy using simulations.</p><p><strong>Results: </strong>Evaluating current drug use, the proportion of individuals classified as exposed increased with the length of the time window for all drugs, reaching a plateau considering a 120-150-day window for statins, glucose-lowering drugs, and selective serotonin reuptake inhibitors, and a 180-300-day window for opioids, whereas no plateau was reached for non-steroidal anti-inflammatory drugs within 360 days. The prevalence of polypharmacy ranged from 21% (10 different 4th level Anatomical Therapeutic Chemical (ATC) groups in 1 year) to 92% (two different 4th level ATC groups in 1 year) depending on the applied definition. In the simulation, the best criterion for identifying polypharmacy required at least two dispensations during the one-year study period for each of at least five drugs, with sensitivity ranging between 0.93 and 1.0, and specificity between 0.72 and 1.0.</p><p><strong>Conclusions: </strong>Time windows up to 120 days are too short to identify baseline drug use in the Danish setting. How polypharmacy is defined significantly influences its estimate, suggesting a need to use multiple definitions in each study.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 5","pages":"e70384"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856978","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":"A Systematic Review to Summarize and Critically Appraise Existing Phenotype Libraries Using Electronic Health Records.","authors":"Sima Mohammadi, Cori Campbell, Miriam C J M Sturkenboom, Tiago A Vaz","doi":"10.1002/pds.70378","DOIUrl":"https://doi.org/10.1002/pds.70378","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;Pharmacoepidemiology and population health studies using electronic health care records (EHRs) must define study variables through available electronic data. These variables are operationalized through phenotypes, which are a defined set of criteria used to identify specific traits or medical conditions. There is diversity across phenotype libraries (collections of code lists or algorithms) which intend to standardize these sets of criteria. This review aimed to characterize the landscape of phenotype libraries and how phenotypes are constructed, validated, managed, and reused across research settings.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a systematic review of existing phenotype libraries to appraise their attributes. We systematically searched three databases (Scopus, PubMed, and Web of Science) up to November 2025 to identify studies on key characteristics of phenotype libraries. The search combined Medical Subject Headings (MeSH) terms related to \"electronic health record,\" \"phenotype algorithm,\" and \"phenotype library\". A structured hand search was performed to identify relevant web-based resources without accompanying publications to ensure comprehensive inclusion of libraries available to date. We extracted information on library size, vocabularies, phenotype construction methods, validation practices, management, and portability.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Of 336 articles, 37 met eligibility criteria for full-text review, of which 25 were excluded because they were not EHR-based phenotype libraries (representing single algorithms, genomic resources, or study-specific phenotypes rather than reusable libraries), leaving 10 unique libraries described across 12 articles. A structured hand search identified seven more libraries. In total, 17 phenotype libraries met the inclusion criteria, including Education and Child Health Insights from Linked Data (ECHILD) Phenotype Code List Repository, Centralized Interactive Phenomics Resource (CIPHER), Chronic Condition Data Warehouse (CCW), ClinicalCodes Library, Clinical Classifications Software Refined (CCSR), ComPLy, CALIBER (Health Data Research UK (HDR UK) Phenotype Library or CALIBER), Jigsaw Algorithm Repository (JAR), Manitoba Centre for Health Policy (MCHP) Concept Dictionary, Open CodeLists, Observational Health Data Sciences and Informatics (OHDSI) ATLAS, PheCode, Phenotype KnowledgeBase (PheKB), Phenotype Execution and Modeling Architecture (PhEMA) Workbench, PheMap, Sharing and Reusing Computable Phenotype Definitions (SharePhe), Value Set Authority Center (VSAC). Libraries varied substantially in scope, size, and phenotype representation, including rule-based algorithms, probabilistic phenotypes, and standardized code groupings. Validation practices were heterogeneous and reported only for a subset of libraries. All the libraries utilized a web-based platform and met at least the minimum requirements for library management, including phenotype def","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 5","pages":"e70378"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13110926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777973","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":"The EUROmediCAT Network and Databases: A Resource for Pharmacovigilance in Pregnancy.","authors":"Helen Dolk, Christine Damase-Michel, Joan Morris, Amanda Neville, Ester Garne, Sue Jordan, Anke Rissmann, Alessio Coi, Deirdre Folan, Dieuwke Broekstra, Jennifer M Broughan, Lea Bruneau, Clara Cavero-Carbonell, Elly den Hond, Miriam Gatt, Mika Gissler, Babak Khoshnood, Anna Latos Bielenska, Hedvig Nordeng, Ljubica Odak, Mary O'Mahony, Isabelle Perthus, J Luke Richardson, Florence Rouget, Joanna Sichitiu, David Tucker, Natalya Zymak-Zakutnya, Maria Loane","doi":"10.1002/pds.70360","DOIUrl":"10.1002/pds.70360","url":null,"abstract":"<p><strong>Background: </strong>The evidence gap relating to the risk of congenital anomalies (CA) associated with first trimester medication exposure in pregnancy is well recognized.</p><p><strong>Aims: </strong>We describe the EUROmediCAT network and databases, and the methodological approach to pregnancy pharmacovigilance.</p><p><strong>Material and methods: </strong>Multidisciplinary expertise includes CA diagnosis and epidemiology, pharmacoepidemiology, pharmacology and teratology. The EUROmediCAT central database comprises standardized data from 19 EUROCAT CA registries in 14 countries, including more than 40 000 CA cases 1995-2021 with first trimester medication exposure data recorded, and a population coverage of 14.6 million births, growing by more than 650 000 births per year. The distributed database enables federated data analysis across eight countries which can link data from CA registries to electronic healthcare data, with population coverage of up to 900 000 births per year for linkage to maternal prescriptions, of which 300 000 births per year for linkage also to data on all births.</p><p><strong>Results: </strong>The databases have enabled a variety of study designs: case-malformed control studies, cohort studies, disease cohort studies, signal detection studies, prevalence and ecological studies, and medication utilization studies.</p><p><strong>Discussion: </strong>A key strength is that studies of CA risk can address accurately the specificity of risk by type of CA.</p><p><strong>Conclusion: </strong>EUROmediCAT presents a unique data and expert resource for tackling the enormous evidence gap regarding the safety of medication during pregnancy.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 5","pages":"e70360"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13129265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147778002","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":"Comparative Analysis of Potential Side Effects of Targeted Oral Hypoglycemic Agents Using Spontaneous Adverse Event Reports and Social Media Data.","authors":"Se-Hoon Oh, Dong-Young Park, Yun-Kyoung Song","doi":"10.1002/pds.70386","DOIUrl":"https://doi.org/10.1002/pds.70386","url":null,"abstract":"<p><strong>Aim: </strong>Adverse events (AEs) detected in tweets and in the FDA Adverse Event Reporting System (FAERS) provide valuable insights into patient experiences with oral hypoglycemic agents including sodium-glucose transporter 2 (SGLT2) and dipeptidyl peptidase-4 (DPP4) inhibitors. This study compared the side effects identified from tweets with those in the FAERS to identify the AEs associated with each drug.</p><p><strong>Materials and methods: </strong>We collected AE data through tweet and the FAERS during 2017-2021. Relevant sentences in the tweets were annotated and manually labeled to identify AE terms. The data obtained from both sources were categorized according to the System Organ Class (SOC) of the Medical Dictionary for Regulatory Activities. Renal and urinary disorders were defined as the index comparator with a value of 1.0. The relative frequency of a side effect compared with the index comparator was obtained.</p><p><strong>Results: </strong>Both drugs showed similarities in high-frequency SOCs. The largest difference between the two datasets for DPP4 inhibitors was observed for the Cardiac disorders category. It ranked 12th in FAERS but 1st in tweets data, showing a marked difference in index values (FAERS 0.75, Tweet 10.80). For the SGLT2 inhibitor, the most evident difference was in the Surgical and medical procedures category. In this category, the index from FAERS was 0.26, while that from tweets was 3.49, ranking 12th and 1st, respectively.</p><p><strong>Conclusions: </strong>Despite the differences in the quantity and types of side effects between the two sources, we were able to identify which clinically significant side effects patients were concerned about and worried about.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 5","pages":"e70386"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841270","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":"Analysis of Mandatory Post-Marketing Surveillance Studies Supports Revised Regulatory Requirements in Korea.","authors":"Kevin Wolter, Seung-Hee Jeong, Ju-Won Woo, Eunsol Kim, Yoosun Lee, Sera Cha, Evelyn Moy, Rod Junor","doi":"10.1002/pds.70382","DOIUrl":"https://doi.org/10.1002/pds.70382","url":null,"abstract":"<p><strong>Purpose: </strong>The objective of this analysis was to determine the contribution to the understanding of product benefit/risk made by non-randomized, observational post-marketing surveillance (PMS) studies previously required by the Ministry of Food and Drug Safety (MFDS) re-examination system and conducted by Pfizer in Korea over 2000-2024.</p><p><strong>Methods: </strong>A retrospective analysis of all Pfizer Korea PMS studies during 2000-2024 was performed, covering a wide range of therapy areas. Available Pfizer clinical study reports and re-examination reports were reviewed for sample sizes, study periods, and key safety and effectiveness findings.</p><p><strong>Results: </strong>Twenty-four studies that enrolled 21 179 Korean participants were identified. Original sample sizes assigned by MFDS were typically either 600 or 3000 participants, but enrollment challenges were common and approximately half of the PMS studies were permitted to reduce sample size. Mean study duration (FSFV-LSLV) was 3.8 years. Safety findings were consistent with existing global safety data, with no clinically significant new safety information being generated from the PMS studies.</p><p><strong>Conclusions: </strong>PMS conducted by Pfizer in Korea were often challenging to recruit and generated data that were consistent with prior global data, with no evidence of clinically meaningful differences in Korean patients. These findings support MFDS's recent transition to a risk management plan (RMP) framework, with PMS only as needed, reducing mandatory requirements for newly approved drug products. Furthermore, when a PMS study is necessary to address a specific scientific uncertainty, MFDS allows individual determination of the sample size, which will improve the feasibility of conducting the study.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 5","pages":"e70382"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147778029","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 Safety: Being Vigilant… or Proactive?","authors":"Alain Braillon","doi":"10.1002/pds.70385","DOIUrl":"https://doi.org/10.1002/pds.70385","url":null,"abstract":"","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 5","pages":"e70385"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147778049","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":"Beta Blocker Use and Total Knee Arthroplasty Among United States Medicare Beneficiaries.","authors":"Shailina Keshwani, Haesuk Park, Wei-Hsuan Lo-Ciganic, Roger B Fillingim, Steven M Smith","doi":"10.1002/pds.70387","DOIUrl":"https://doi.org/10.1002/pds.70387","url":null,"abstract":"<p><strong>Background/objectives: </strong>Preclinical evidence suggests beta blockers may reduce cartilage degradation and delay knee osteoarthritis (OA) progression. While beta blockers are widely used in patients with hypertension, their potential role in preventing total knee arthroplasty (TKA) is unclear. Therefore, we assessed the association between beta blocker use and TKA in knee OA patients with hypertension.</p><p><strong>Methods: </strong>We conducted a nested case-control study using a nationally representative sample of Medicare beneficiaries with newly diagnosed knee OA and prevalent hypertension from 2011 to 2020. Beneficiaries who underwent TKA were defined as cases, while those without TKA were defined as controls. Cases and controls were matched at a 1:4 ratio based on pre-specified criteria using incident density sampling. We measured binary (exposed/unexposed) and cumulative exposure of beta blockers during 6 months before TKA using total standardized daily doses (TSDD) for each patient, categorized as unexposed (0), < 1-200, 201-400, 401-600, 601-900, > 900. Confounding was addressed using propensity score adjustment and stratification for the binary exposure and direct covariate adjustment for cumulative exposure in conditional logistic regression models.</p><p><strong>Results: </strong>We included 30 338 beneficiaries with TKA and 106 145 matched controls. The mean age (SD) was 74.4 (5.5) years, and 67.1% were women in both groups. There was no significant association between beta blocker use and odds of TKA (adjusted OR [aOR] 1.01; 95% CI, 0.97-1.02) compared with unexposed individuals. Smilarly, no cumulative exposure category was associated with TKA risk (TSDD: < 1-200 [aOR, 1.01; 95% CI,0.97-1.04]; TSDD: 201-400 [aOR 1.00; 95% CI, 0.96-1.05]; TSDD: 401-600 [aOR, 1.02; 95% CI, 0.96-1.08]; TSDD: 601-900 [aOR 0.94; 95% CI, 0.87-1.00]; and, TSDD: > 900 [aOR 0.99; 95% CI, 0.91-1.08]), compared with the unexposed group.</p><p><strong>Conclusion: </strong>We found no evidence to support that beta blocker exposure reduces the likelihood of TKA.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 5","pages":"e70387"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841284","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}