Pharmacoepidemiology and Drug Safety最新文献

{"title":"Nexus: A Deterministic Linkage Framework for Constructing Longitudinal Real-World Data in Brazil's Public Health System.","authors":"Julio Cesar Barbour Oliveira, Tulio Tadeu Rocha Sarmento, Daniela Mayumi Usuda Prado Rocha, Erick Kazu Açakura, Gabriela Naomi Ishibe, Caroline Tianeze de Castro, Rodrigo Gonçalves Queijo, Giovanna Bertelli de Gouveia, João Gabriel Rego, Ana Luiza Bierrenbach","doi":"10.1002/pds.70391","DOIUrl":"10.1002/pds.70391","url":null,"abstract":"<p><strong>Background: </strong>Brazil's Unified Health System (SUS) does not provide a person identifier in the publicly available inpatient system (SIH) microdata, limiting longitudinal analyses. We propose a deterministic linkage framework (Nexus) designed to construct longitudinal real-world datasets under these structural constraints.</p><p><strong>Methods: </strong>We first established a cloud-based preprocessing pipeline using a Lakehouse architecture to ingest, standardize, and harmonize raw administrative data from the Ministry of Health's public repository of national databases, 2008-2024, into reproducible inpatient and outpatient tables. Auxiliary sources were integrated to enrich metadata. SIA records containing the encrypted National Health Card (CNS) were curated using internal consistency filters for sex, date of birth (DOB), and postal code (CEP). Linkage with SIH applied a quasi-identifier (CEP, DOB, sex) with an α-shrinkage rule to exclude ambiguous high-density cells, prioritizing specificity by retaining only unique matches. Candidate cohorts varying by α and start year were compared using data quality diagnostics.</p><p><strong>Results: </strong>From 224.7 M unique CNS in SIA (2008-2024), curation yielded 12.9 M patients. Exact-match linkage of SIH hospitalizations produced a final Nexus cohort of 9.2 M patients. Using α = 40 and a 2012 start was associated with improved temporal consistency and stable disease event fractions.</p><p><strong>Conclusions: </strong>Nexus demonstrates that a conservative, transparent deterministic linkage framework can be used to construct a longitudinal cohort under structural data constraints. Coverage is reduced-mainly because CEP is concentrated in high-complexity claims-resulting in a selected subpopulation enriched for specialized care. Accordingly, Nexus is suited for longitudinal analyses of treatment pathways and outcomes, but not for population-level inference or incidence estimation.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 6","pages":"e70391"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147964374","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":"Atypical Shoulder Pain and Dysfunction After Vaccinations Reported to the Vaccine Adverse Event Reporting System (VAERS) January 1, 2018, Through October 31, 2022.","authors":"Elaine R Miller, Paige Marquez, Getahun Aynalem, Charles Licata, Mary Nythel Rubin, Emma Freeborn, Shaeyla Davis, Amy Roberts, Manisha Poudyal, Sehwa S Kim, Heather Cooper, Monica Rounds, Liza Mozingo, Sandra Amouzou, Bicheng Zhang, Sara Dunbar, Valerie Caraballo, Aisha Barre, Rachel McVey, Caitlin Stibbe, Margaret Harris, Jennifer Davis, Vanessa Ramirez, Michael Lemperle, Pedro L Moro","doi":"10.1002/pds.70397","DOIUrl":"10.1002/pds.70397","url":null,"abstract":"<p><strong>Background: </strong>Shoulder injury related to vaccine administration (SIRVA) may result from improper vaccination technique when a vaccine is given into or near the subacromial bursa or synovium, which may result in shoulder pain, dysfunction, and long-lasting impairment.</p><p><strong>Methods: </strong>We searched the Vaccine Adverse Event Reporting System for reports received January 1, 2018, through October 31, 2022, describing atypical shoulder pain and dysfunction. We used the National Vaccine Injury Compensation Program's definition for SIRVA: onset within 48 h after vaccination, with pain and decreased range of motion in the vaccinated arm. We added the requirement that symptoms last ≥ 7 days.</p><p><strong>Results: </strong>Based on automated search, 26 061 (2.4%) were potential cases. In reviewing all 1819 serious and a random sample of 200 nonserious reports, 580 (32%) serious and 38 (19%) nonserious reports were potential SIRVA cases for a reporting rate of approximately 0.5%. SIRVA was rare in children and serious reports were most frequent among adult females (74%). A contributing factor was vaccine given \"too high\" in the arm in 68%. Interference/inability to perform activities of daily living and/or absenteeism from work was reported in 285 (64%) serious reports.</p><p><strong>Conclusions: </strong>SIRVA is a rarely reported but important vaccine adverse event; symptoms can impact activities of daily living and work. Its greater frequency in female sex, rarity in children, and the association with the vaccine administered too high in the arm are consistent with previous studies. Prevention strategies should be prioritized, including vaccinator training to adhere to proper vaccine administration techniques.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 6","pages":"e70397"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147942319","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":"Trajectories of Treatment Disruption for Chronic Outpatient Medications for U.S. Veterans During Drug Shortages.","authors":"Katie J Suda, Xinhua Zhao, Sherrie L Aspinall, Yaming Li, Katherine Callaway Kim, Francesca E Cunningham, Taylor L Boyer, Tate W Miner, Clara Kima, Walid F Gellad, Peter A Glassman, Chester B Good, Felicia Skelton, Mina Tadrous, Carolyn T Thorpe","doi":"10.1002/pds.70393","DOIUrl":"10.1002/pds.70393","url":null,"abstract":"<p><strong>Introduction: </strong>Although drug shortages for outpatient chronic conditions commonly occur, population-level data on how they impact patients' ability to refill prescriptions is scarce. We sought to identify distinct patterns of refill adherence following drug shortages and patient- and prescription-level factors associated with adherence trajectories reflecting potential shortage-related treatment disruption.</p><p><strong>Methods: </strong>We retrospectively analyzed panel data assembled from 2017 to 2020 Veterans Health Administration (VHA) electronic health record data. Patients were included if they were baseline users of medications subject to a shortage within VHA. Group-based trajectory modeling was applied to users' monthly proportion of days covered (PDC) values from 6-months before to 6-months after the reported drug supply chain disruption. Patient demographics and medication characteristics were compared between identified trajectory groups using multivariable logistic regression.</p><p><strong>Results: </strong>Among 1.5 million episodes of medication use (representing 1.3 million unique Veterans) for 29 medications in shortage in VHA, 6.3% were for female patients and the mean age was 66.4 ± 12.8 years. A 4-group trajectory model had the best fit: High Adherence (69.2% of observations), Moderate Adherence (14.1%), Potential Shortage-Related Disruption (8.5%), and Pre-Shortage Disruption (8.3%). Drug characteristics (drug class, number of manufacturers) were more strongly associated than patient characteristics with having Potential Shortage-Related Treatment Disruption vs. High Adherence.</p><p><strong>Conclusions: </strong>We identified 4 trajectories of refill adherence for medications subject to VHA drug shortages, with 8.5% of users of affected drugs exhibiting a trajectory consistent with shortage-related treatment disruption. Drug characteristics may modify whether drug shortages lead to treatment disruption in VHA.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 6","pages":"e70393"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147974420","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":"The Association Between MOG-IgG Positivity and mRNA SARS-CoV-2 Vaccination in Denmark: A Self-Controlled Case Series Study.","authors":"Tine Iskov Kopp, Anne Katrine Andreasen, Viktoria Papp, Mette Hjorslev Knudgaard, Heidi Jeannet Graff, Michelle S Clement, Nicklas Hasselblad Lundstrøm, Stine Ulsø, Mona El-Sayed Hervig, Charlotte Wessel Skovlund","doi":"10.1002/pds.70403","DOIUrl":"10.1002/pds.70403","url":null,"abstract":"<p><strong>Purpose: </strong>Spontaneous reporting of a possible link between myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) and mRNA SARS-CoV-2 vaccination warrants further examination. Hence, the objective of this study was to investigate the association between MOG-IgG positivity as a proxy for MOGAD and mRNA SARS-CoV-2 vaccination in the Danish population.</p><p><strong>Methods: </strong>We applied the self-controlled case series study using Danish nationwide health registers. The study population consisted of all Danish residents who were offered an mRNA COVID-19 vaccination and had a first positive MOG-IgG test result between November 1, 2020 to December 31, 2023.</p><p><strong>Results: </strong>Among 5.9 million individuals eligible for SARS-CoV-2 vaccination, we identified 111 incident events of MOG-IgG positivity in the study period of which 28 (25%) occurred in children. We found no association between mRNA SARS-CoV-2 vaccination and MOG-IgG positivity in adults, but an increased risk-although based on small numbers-was found in children below 18 years of age (incidence rate ratio = 8.07, 95% confidence intervals: 3.07-21.21). If the observed association reflects a causal effect, the estimated number of excess MOG-IgG positive events attributable to mRNA COVID-19 vaccination in Denmark was 4.38 per 1 000 000 exposed children.</p><p><strong>Conclusions: </strong>These results suggest an increased risk of MOG-IgG positivity after mRNA SARS-CoV-2 vaccination in children, but not in adults. The number of additional MOGAD events attributable to mRNA SARS-CoV-2 vaccination in children is very low and further studies are needed to confirm these findings.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 6","pages":"e70403"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148138631","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":"Exploring Opioid Prescriber Decision-Making: A Qualitative Study.","authors":"Jamie L Smith, Molly M Jeffery, Jason S Egginton, Kim Adams, Sey V Oloyede, Jessica J McCoy, Kathleen J Yost, Blair Coleman, Sara Eggers, Katherine Hyatt Hawkins Shaw, Megan Moncur, W Michael Hooten, Jennifer L Ridgeway","doi":"10.1002/pds.70402","DOIUrl":"10.1002/pds.70402","url":null,"abstract":"<p><strong>Purpose: </strong>To explore the opioid decision-making process of prescribers in primary care, surgery, and subspecialty pain management.</p><p><strong>Methods: </strong>This was a multistage qualitative-qualitative study with clinicians involved in opioid prescribing and management from a single healthcare organization with locations in Minnesota, Florida, Arizona, and Wisconsin. Clinicians in this study included physicians, nurse practitioners (NPs), and physician assistants (PAs) practicing in primary care, surgery, or pain medicine. The interview guide was organized in three domains of a conceptual model for opioid use: (1) prescriber characteristics, (2) patient characteristics, and (3) practice environment characteristics. Individual interviews (N = 20) were performed first, and data were summarized using a rapid template-based approach. Subsequently, focus groups (FGs) (N = 4) were conducted with an additional 21 clinicians to confirm and explore interview results. Data from interviews and FGs were analyzed using a common codebook.</p><p><strong>Results: </strong>Findings were organized as decision factors into the three domains. Factors in the prescriber domain included characteristics such as formal pain management training, as well as factors that influenced knowledge and beliefs (e.g., advice from or observation of supervising clinicians and expert colleagues). Decision factors in the patient domain included patient pain etiology, comorbid medical or mental health conditions, and demographic characteristics. Clinicians' perceptions of these factors, such as viewing older age as having lesser risk for opioid misuse, influenced prescribing decisions. Clinicians also described challenges associated with \"legacy patients\" whose therapy was previously managed by a different clinician. Primary care clinicians, in particular, expressed difficulties managing post-surgical or trauma-related pain after care transition. Relevant decision factors reported by prescribers in the practice environment domain included guidelines and practice oversight. Most participants reported practicing in an environment that promoted conservative opioid use and having access to standardized institutional guidelines that reduced perceived decision-making burden. Clinicians described how they used prescribing guidelines to help them communicate with patients about opioid use and prescribing decisions.</p><p><strong>Conclusions: </strong>Intersecting prescriber, patient, and practice environment factors shape opioid analgesic prescribing decisions. Available resources in the practice environment, including peer input and institutional guidelines, may support clinician decision-making and conversations with patients at the point of care, including in cases where patients have complex histories or personal characteristics that influence decision making.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 6","pages":"e70402"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148055197","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":"Optimizing Use of Real-World Data in Regulatory Decision Making for Medical Devices Used in Surgical Procedures.","authors":"Guy Cafri, Florence Bourgeois, Paul Coplan","doi":"10.1002/pds.70407","DOIUrl":"10.1002/pds.70407","url":null,"abstract":"<p><strong>Purpose: </strong>In the United States, the Food and Drug Administration has provided guidance on the contexts in which real-world evidence (RWE) can be used to support regulatory decisions for medical devices.</p><p><strong>Methods: </strong>In this paper, we review different sources of real-world data (RWD) for medical devices used in surgical procedures and how to optimize the design and analysis features of RWD studies to maximize the strength of RWE. The design and analysis of a study are critical to ensuring that the RWE generated from the RWD can ultimately be used to support a regulatory decision or fulfill a commitment for a medical device. We consider several topics relevant to medical device RWE in our review: misclassification and measurement error, causal inference, and incomplete follow-up.</p><p><strong>Results: </strong>Some key challenges include indication and outcome misclassification in non‑registry data, tenuous assumptions of single‑arm designs, device‑ and surgeon‑level confounding in comparative studies, and potentially informative loss to follow‑up from censoring (e.g., insurance termination).</p><p><strong>Conclusion: </strong>The review is intended as a guide to researchers and regulators interested in generating or evaluating medical device RWE for regulatory purposes.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 6","pages":"e70407"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13243975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199721","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":"Prevalent-New User Design for Biosimilar Safety Using Saudi Real-World Data.","authors":"Ohoud Almadani, Almaha Alfakhri, Ibrahim Asiri, Abdulrahman Alturaiki, Abdulrahman Alrashid, Turki Althunian","doi":"10.1002/pds.70388","DOIUrl":"10.1002/pds.70388","url":null,"abstract":"<p><strong>Objective: </strong>Incidents of infections associated with biosimilar biological disease-modifying antirheumatic drugs (bDMARDs) have been communicated to the Saudi Food and Drug Authority (SFDA). This study aimed to evaluate the infection risk related to biosimilar bDMARDs and assess the applicability of the prevalent new-user design within a Saudi cohort.</p><p><strong>Methods: </strong>Using the Saudi Real-World Evidence Network (SRWEN), patients aged ≥ 14 years who initiated or switched to biosimilar versus reference bDMARDs between 2016 and 2025 were identified. A prevalent new-user design that accounted for prior exposure to reference bDMARDs was implemented. Time-conditional propensity score (TCPS) matching (1:1 and 1:3) balanced baseline covariates. The study outcome was the risk of any infection, identified via ICD-10 codes in the main analysis, in addition to laboratory results and antimicrobial prescriptions in the sensitivity analyses. Hazard ratios (HRs) were estimated using Cox proportional hazards models with robust sandwich estimators.</p><p><strong>Results: </strong>Among 5721 patients contributing 59 856 treatment episodes, 2178 were biosimilar initiators and 2909 were switchers (from the reference product). Adalimumab accounted for 69.5% of use. Over a median 1.6-year follow-up, infection incidence rates were comparable between reference and biosimilar groups (456.7 vs. 422.0 per 1000 person-years). Adjusted HRs showed no significant difference in infection risk (HR 0.89; 95% CI 0.57-1.39, p-value: 0.61), with consistent findings across sensitivity and disease-matched analyses where the adjusted HR was 0.87 (95% CI 0.51-1.50, p-value: 0.62).</p><p><strong>Conclusion: </strong>In this real-world Saudi cohort, no statistically significant difference in infection risk was observed between biosimilar and reference bDMARD. Larger studies and further evaluation of the prevalent new-user design are needed to enhance post-marketing biosimilar surveillance in the region.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 6","pages":"e70388"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148034163","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 Feasibility Assessment of the FDA Adverse Event Reporting System for the Detection of Cannabis-Related Safety Signals.","authors":"Priscilla O M V Lopes, Cory S Harris, Christopher A Gravel","doi":"10.1002/pds.70392","DOIUrl":"10.1002/pds.70392","url":null,"abstract":"<p><strong>Background: </strong>The applicability of spontaneous reporting systems such as the US Food and Drug Administration Adverse Event Reporting System (FAERS) to detect cannabis-related safety signals remains unclear due to the potential for discrepant reporting patterns between pharmaceutical and non-pharmaceutical cannabis-derived products (CDPs).</p><p><strong>Methods: </strong>We conducted a descriptive analysis of seven groups of CDP reports submitted to FAERS between 1999 and 2023 to investigate product definitions and reporting patterns. We then performed hypothesis-free disproportionality analyses using reporting odds ratio, proportional reporting ratio, and information component for pharmaceutical cannabidiol (CBD) and non-pharmaceutical CBD reports to assess differences in signal detection profiles, potential exposure misclassification, and the influence of reporting context.</p><p><strong>Results: </strong>We identified 42 530 reports related to CDPs, characterized by highly heterogeneous terminology and variable reporting patterns by product type, reflecting the real-world CDP usage. Epidiolex reports often involved pediatric patients, whereas non-pharmaceutical CBD reports were more frequently associated with older adults and concomitant product use. Disproportionality analysis showed divergent signal profiles, with strong seizure-related events predominating for Epidiolex and a broader range of signals, including neoplasm-related and neurological events, observed for non-pharmaceutical CBD. These differences likely reflected variations in CDP indication and utilization and reporting behaviors.</p><p><strong>Conclusions: </strong>This study showed that signal detection using FAERS has potential feasibility for CDP safety surveillance. However, unique challenges related to exposure definitions, reporting patterns, motivation for utilization, and the need for a robust study design must be addressed to ensure reliable safety signal detection.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 6","pages":"e70392"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13172948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147932442","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":"Early Identification of Differentiation Syndrome During ATRA and Arsenic Therapy in Pediatric NHR-APL: Insights From a 14-Year Multicenter Cohort.","authors":"Zhong Fan, Liang-Chun Yang, Yi-Qiao Chen, Wu-Qing Wan, Hui-Rong Mai, Li-Hua Yang, He-Kui Lan, Dun-Hua Zhou, Wan-Li Li, Bi-Yun Guo, Fei He, Liu-Hua Liao, Hui-Qin Chen, Zi-Jun Zhen, Xiang-Ling He, Xiao-Qin Feng, Guo-Hua Chen, Xun-Qi Ji, Mo Chen, Qiao-Ru Li, Xing-Jiang Long, Chuan Tian, Ying Fu, Xiu-Ya Huang, Jie-Si Luo, Dan-Ping Huang, Li-Na Wang, Yu Li, Bin Li, Xue-Qun Luo, Li-Bin Huang, Yan-Lai Tang, Xiao-Li Zhang","doi":"10.1002/pds.70390","DOIUrl":"10.1002/pds.70390","url":null,"abstract":"<p><strong>Background: </strong>The combination of all-trans retinoic acid (ATRA) with arsenic trioxide (ATO) has dramatically improved the cure rate of acute promyelocytic leukemia (APL). However, differentiation syndrome (DS) remains a significant cause of early mortality in APL patients. This severe complication typically occurs during induction therapy with ATRA and/or ATO. Early prediction and timely intervention are crucial to reducing DS-related mortality. This study aimed to identify risk factors for DS and develop a predictive model tailored to children with non-high-risk (NHR) APL.</p><p><strong>Methods: </strong>We conducted a multicenter retrospective analysis of 166 pediatric NHR-APL patients treated between 2011 and 2024. Clinical characteristics were compared between DS and non-DS groups. Logistic regression was used to identify independent predictors, and a nomogram was developed based on these variables. The model was evaluated using the area under the curve (AUC) and decision curve analysis (DCA).</p><p><strong>Results: </strong>Seventeen patients (10.2%) developed DS during induction. Multivariate analysis identified five independent risk factors: female sex, non-chemotherapy group, BCR subtype 3, elevated peripheral promyelocyte proportion (≥ 44%), and platelet count (≥ 20 × 10⁹/L). The predictive nomogram achieved an AUC of 0.89 in the training set and 0.75 in the validation set. DCA demonstrated favorable clinical utility of the model.</p><p><strong>Conclusions: </strong>We developed and validated the first nomogram for predicting DS in pediatric NHR-APL. This tool enables early risk stratification and may guide clinical decision-making to reduce early mortality.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 6","pages":"e70390"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148212159","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":"Use Patterns of Novel Janus Kinase Inhibitors After the First Safety Alerts: A Nationwide Register-Based Time Series Analysis.","authors":"Jarno Rutanen, Pekka Heino, Kati Sarnola, Terhi Kurko","doi":"10.1002/pds.70389","DOIUrl":"10.1002/pds.70389","url":null,"abstract":"<p><strong>Purpose: </strong>Janus kinase inhibitors (JAKi) are medicines used to treat inflammatory rheumatic musculoskeletal diseases (IRMDs) and inflammatory bowel diseases (IBDs). In Europe, JAKis received marketing authorisation in 2017 for rheumatoid arthritis. Subsequently, the European Medicines Agency (EMA) issued multiple safety alerts concerning this drug class. We aimed to examine how the use of JAKis developed in Finland.</p><p><strong>Methods: </strong>We conducted a retrospective time series analysis on the initiations and use of JAKis in the treatment of IRMD and IBD, utilising the national medicines reimbursement registry 2018-2023, including nearly all JAKi prescriptions. We assessed the initiators' age, line of treatment and atherosclerotic risk factors.</p><p><strong>Results: </strong>Between 2018 and 2023, the prevalence of JAKi use increased from 0.14 to 0.43/1000 inhabitants, from 756 to 1740 among IRMD patients and from 11 to 672 among IBD patients. In IRMD, JAKis were rapidly adopted with 677 initiations in 2018, declining to 328 initiations in 2023. The corresponding numbers in IBD were 11 in 2018 and 358 in 2023. The mean age of IRMD patients initiating JAKis decreased from 54 years in 2021 to 41 years in 2023, while IBD patients' mean age changed from 42 to 39 years. In 2020, 52% of IRMD Patients Initiated JAKi in second-line of treatment but by 2023, this decreased to 31%. Prevalence of atherosclerotic risk factors declined.</p><p><strong>Conclusions: </strong>The uptake of JAKis among IRMD patients were initially fast. After safety alerts, initiation rates declined and shifted towards younger patients with fewer atherosclerotic risk factors. In contrast, the uptake of JAKis among IBD patients increased steadily.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 6","pages":"e70389"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147974401","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}