Pharmacoepidemiology and Drug Safety最新文献

{"title":"The Risk of Hypothyroidism With the Use of GLP-1 Receptor Agonists in Saudi Arabia.","authors":"Almaha Alfakhri, Ohoud Almadani, Raseel Alroba, Adel Alrwisan, Omar Alshaya, Yasser Albogami","doi":"10.1002/pds.70315","DOIUrl":"https://doi.org/10.1002/pds.70315","url":null,"abstract":"<p><strong>Aim: </strong>Preclinical studies have suggested that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may induce thyroid gland hyperplasia, raising concerns about potential thyroid-related risks. Given their increasing use and the limited evidence on thyroid safety, this study assessed the association between GLP-1RA use and the incidence of hypothyroidism using real-world data.</p><p><strong>Methods: </strong>We conducted an active-comparator, new-user cohort study using the Real-World Evidence Research Network (SRWEN) (2016-2023). Adults (≥ 18 years) initiating GLP-1RAs or dipeptidyl peptidase-4 inhibitors (DPP-4is) were followed from first prescription until hypothyroidism, treatment discontinuation, switching, death, or study end. Hypothyroidism was identified through ICD-10 codes or levothyroxine prescriptions. Inverse probability of treatment weighting was applied to adjust for confounding, and weighted Cox proportional hazards models were used to estimate hazard ratios (HRs). RStudio 4.4.0 was used for analyses.</p><p><strong>Results: </strong>A total of 47 017 patients were included (6800 GLP-1RA users; 40 217 DPP-4i users). GLP-1RA users were younger (mean age 50 vs. 58 years) and more often female. The incidence rate of hypothyroidism was 128 per 10 000 person-years in GLP-1RA users compared to 150 per 10 000 person-years in DPP-4i users. GLP-1RA use was not associated with a statistically significant risk of hypothyroidism (adjusted HR 1.04, 95% CI 0.69-1.57). Sensitivity analyses extending follow-up by 30 and 60 days yielded consistent findings.</p><p><strong>Conclusion: </strong>In this real-world analysis, GLP-1RA use was not associated with an increased incidence of hypothyroidism compared to DPP-4is. Findings were consistent across sensitivity and subgroup analyses. Although findings do not suggest a short-term risk, longer-term studies are warranted to further evaluate thyroid safety.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 1","pages":"e70315"},"PeriodicalIF":2.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906478","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 Challenges for Pharmacoepidemiologists Identifying Migraine in Electronic Healthcare Data Sources: A Systematic Literature Review.","authors":"Joan Forns, Alicia Abellan, Nuria Riera-Guàrdia, Andrea V Margulis, Elena Rivero-Ferrer","doi":"10.1002/pds.70278","DOIUrl":"https://doi.org/10.1002/pds.70278","url":null,"abstract":"<p><strong>Purpose: </strong>Ascertaining migraine in electronic healthcare data is challenging because of likely diagnosis underrecording and treatment with over-the-counter analgesics, which cannot be used as disease proxies. Algorithm-identified migraine prevalence may depend on algorithm characteristics and target population.</p><p><strong>Methods: </strong>To describe migraine-identifying algorithms implemented in electronic healthcare data sources and summarize validation results and observed migraine prevalence, we searched PubMed for peer-reviewed, English-language, original research articles that identified migraine in adults using electronic algorithms in electronic healthcare data. We summarized algorithms, validation results, and migraine prevalence (PROSPERO: CRD42023491279).</p><p><strong>Results: </strong>Of 360 unique titles and abstracts, 50 articles (14%) were selected for full-text review; of them, 41 articles (82%) were finally included: 16 were studies conducted in Europe, 13 in North America, and 12 in Asia. Sixteen studies (39%) identified migraine only using diagnosis codes, 5 (12%) only treatments, 9 (22%) diagnosis and/or treatment codes, and 11 (27%) diagnosis codes, treatments, and setting (e.g., primary care, specialist consultation). Reported migraine prevalence in the general population ranged between 4% and 17%. Only two studies reported validation results: one identified prevention-eligible patients with migraine (positive predictive value [PPV] = 97%), and one identified migraine on the basis of calculated probabilities with PPVs between 74% and 92%.</p><p><strong>Conclusion: </strong>Finding patients with migraine is feasible in various types of data sources; preferred algorithms vary; algorithm performance is mostly unknown. Identifying chronic migraine or other complex types of migraine requires combining diagnosis codes, treatments, and care settings, which is possible in only some data sources.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 12","pages":"e70278"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145661326","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":"National Trends and Disparities in Herpes Zoster Vaccination Among US Older Adults With Diabetes, 2008-2023.","authors":"Chun-Tse Hung, Li-Min Wang, Ding-Cheng Liu, Yu-Chien Hung","doi":"10.1002/pds.70301","DOIUrl":"10.1002/pds.70301","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate trends and disparities in herpes zoster vaccination among US older adults with diabetes.</p><p><strong>Methods: </strong>Data from the 2008 to 2023 National Health Interview Survey were used. Joinpoint regression analysis was performed to analyze trends in herpes zoster vaccination. A multivariable logistic regression model was used to identify factors associated with herpes zoster vaccination.</p><p><strong>Results: </strong>A total of 42 377 participants with diabetes were included, representing approximately 18 million US older adults with diabetes. From 2008 to 2023, the prevalence of herpes zoster vaccination increased nearly tenfold, from 4.2% in 2008 to 42.2% in 2023 (average annual percent change = 14.09, p < 0.01), with similar overall trends observed in adults without diabetes (p = 0.08). Upward trends were also observed across age groups and diabetes types. Several factors, including age, race/ethnicity, region, educational level, health insurance, income, perceived health status, flu and pneumococcal vaccination, comorbid atherosclerotic cardiovascular disease and cancer, were associated with herpes zoster vaccination.</p><p><strong>Conclusion: </strong>Herpes zoster vaccine coverage has surged among US older adults with diabetes over the past 16 years. However, disparities in vaccination remain, underscoring the need for targeted policies and interventions to improve coverage.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 12","pages":"e70301"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12701292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743330","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":"All Lines Is the Right Approach: Selecting Patient Lines of Therapy for an External Comparator Arm.","authors":"Daniel Backenroth, Laura Hester, Stijn Vansteelandt","doi":"10.1002/pds.70262","DOIUrl":"10.1002/pds.70262","url":null,"abstract":"<p><strong>Purpose: </strong>To identify the best method for selecting index dates when constructing external comparator arms (ECAs) from real-world data for comparison with single-arm trials (SATs).</p><p><strong>Methods: </strong>We evaluated four approaches for index date selection-first eligible line, last eligible line, random eligible line, and all eligible lines-using causal inference reasoning, numerical examples and a simulation study. Simulations modeled survival across multiple lines of therapy under scenarios with varying eligibility patterns and treatment effects. Overall survival (OS) estimates comparing SAT and ECA populations were obtained using stratified Cox models and propensity-weighted Cox models, adjusted for line of therapy and patient state.</p><p><strong>Results: </strong>Including all eligible lines produced unbiased OS estimates across scenarios. Selecting the last eligible line introduced substantial bias, while random selection led to moderate bias.</p><p><strong>Conclusions: </strong>Using all eligible lines of therapy for each patient when constructing ECAs minimizes bias and preserves the SAT target population. Alternative methods can lead to biased estimates or, in the case of the first eligible line method, require changes to the clinical question that may shrink the SAT population. We recommend adopting the all eligible lines method with variance correction and adjustment for line of therapy to ensure valid comparative effectiveness analyses.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 12","pages":"e70262"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145637202","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":"Efficacy and Safety of All Monoclonal Antibodies in Moderate-to-Severe Atopic Dermatitis: A Systematic Review and Network Meta-Analysis.","authors":"Wenting Cai, Linlin Fu, Yan Wu, Yao Yao, Jinping Zhang","doi":"10.1002/pds.70268","DOIUrl":"10.1002/pds.70268","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to compare the efficacy and safety of monoclonal antibodies (mAb) for moderate-to-severe atopic dermatitis (AD).</p><p><strong>Methods: </strong>The randomized controlled trials (RCTs) of monoclonal antibodies in the treatment of moderate-to-severe AD were searched in the database of PubMed, Embase, Web of Science and Cochrane Library, up to November 2024. The control group included placebo. The efficacy indicators were the percentage of patients achieving 50%, 75%, 90% improvement in Eczema Area and Severity Index score (EASI-50, EASI-75, EASI-90) and the percentage of patients with an Investigator Global Assessment (IGA) Score of 0 or 1 from baseline until the time of efficacy observation, and the percent change in Pruritus Numerical Rating Scale (NRS), EASI score, SCORing Atopic Dermatitis (SCORAD), and change in Percent Body Surface Area (BSA), Dermatology Life Quality Index (DLQI). The statistical analysis was performed by Stata14 and RevMan5.4. Data processing, network evidence plots, surface under the cumulative ranking curve (SUCRA) ranking, league plots and funnel plots were generated. Risk ratio (RR) and 95% confidence interval (95% CI) were used as effect sizes to analyze binary categorical variables.</p><p><strong>Results: </strong>This study included 32 RCTs with 7588 patients. Spesolimab, Rademikibart, Dupilumab, Amlitelimab were more effective than placebo in EASI-50 (RRs ranging between 1.31 and 22.65), EASI-75(RRs ranging between 1.51 and 36.58), EASI-90(RRs ranging between 3.72 and 5.49), and the percentage of patients in IGA score of 0 or 1 (RRs ranging between 1.78 and 13.36). Dupilumab showed relatively good efficacy according to SUCRA ranking on percent change in NRS, EASI, SCORAD. Dupilumab exhibited a lower incidence of serious adverse events than placebo, and the difference was statistically significant (RR = 0.43, 95% CI 0.30-0.63). Other safety analysis results showed no statistical difference.</p><p><strong>Conclusions: </strong>Through the analysis of the primary efficacy indicators, this network meta-analysis (NMA) study indicated that all monoclonal antibodies performed better than placebo. Based on the results of this study, Spesolimab, Rademikibart, Dupilumab, Amlitelimab were recommended treatment options with relatively good efficacy and safety.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 12","pages":"e70268"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145678436","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":"Measuring Exposure to Opioids Using Self-Reported Medication Use Data Versus General Practitioner Prescription Records in the UK Biobank Study.","authors":"Allison Domingues, Yue Zhai, Marie-Odile Parat, Vivian Viallon, Louisa Degenhardt, Sallie-Anne Pearson, Jifang Zhou, Mahdi Sheikh","doi":"10.1002/pds.70280","DOIUrl":"10.1002/pds.70280","url":null,"abstract":"<p><strong>Purpose: </strong>The ongoing global increase in opioid use necessitates studies examining long-term health impacts. Prospective cohorts frequently rely on self-reported medication use data which may be subject to several types of bias compared to more objective measurements. We evaluated the agreement between two opioid exposure measures in the UK Biobank (UKBB)-self-reported regular use and prescription-based indicators using linked general practitioner (GP) records.</p><p><strong>Methods: </strong>Our analysis included 171 813 UKBB participants with linked prescription records. At baseline, participants reported medications taken regularly (weekly, monthly, every 3 months). We assessed agreement between self-reported regular opioid use and opioid prescription records prior to enrollment across various look-back periods and prescription counts. Logistic regressions assessed factors associated with omission and commission.</p><p><strong>Results: </strong>Agreement was moderate to substantial between self-reported opioid use and prescription records. The strongest agreement was observed for ≥ 3 prescriptions in the past 365 days (Cohen's Kappa = 0.66). Subgroup analysis showed better agreement for analgesic opioids (Kappa = 0.43-0.63) than for non-analgesic opioids (Kappa = 0.25-0.34). Omission odds were highest with increasing months since the last record and lowest for individuals with chronic pain. Commission odds were highest for individuals with chronic pain and lowest in married/partnered individuals.</p><p><strong>Conclusions: </strong>This analysis indicates that self-reported regular opioid use in the UKBB could be a valid indicator for identifying individuals with repeated prescriptions for analgesic opioids in the past year, while also capturing opioid use from non-linked sources. However, agreement was low for non-analgesic opioids, suggesting limited utility of self-report for capturing use of these medications.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 12","pages":"e70280"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12833912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701423","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":"Cardiovascular Effectiveness of Semaglutide Versus Dulaglutide in Type 2 Diabetes.","authors":"Kasper Bonnesen, Uffe Heide-Jørgensen, Diana H Christensen, Timothy L Lash, Lars Pedersen, Reimar W Thomsen, Anthony A Matthews, Morten Schmidt","doi":"10.1002/pds.70276","DOIUrl":"10.1002/pds.70276","url":null,"abstract":"<p><strong>Objective: </strong>Randomized clinical trials show that subcutaneous semaglutide is modestly superior to dulaglutide in reducing HbA1c and body weight, but no trial has compared their effectiveness on hard cardiovascular outcomes. This study aimed to examine whether semaglutide and dulaglutide differ in cardiovascular effectiveness.</p><p><strong>Research design and methods: </strong>This new-user, active-comparator cohort study used nationwide population-based Danish healthcare data to emulate a target trial of adults with type 2 diabetes receiving standard care who initiated subcutaneous semaglutide compared with dulaglutide. Up to five semaglutide initiators were matched to one dulaglutide initiator on a propensity score estimated from 52 variables. The outcome was a major adverse cardiovascular event (MACE), including myocardial infarction, ischemic stroke, heart failure, coronary revascularization, and cardiovascular death. In per-protocol analyses, Aalen-Johansen estimates were used to calculate risks, risk differences, and risk ratios at 3 years, accounting for informative censoring at nonadherence to the assigned treatment via time-varying inverse probability of censoring weights.</p><p><strong>Results: </strong>The semaglutide group included 2535 individuals, and the dulaglutide group 569 (median age [IQR], 61 [52-71] years; 1105 female individuals [36%]). Within 3 years, the risk of MACE was 6.0% (95% CI, 4.5%-7.8%) in the semaglutide group and 6.2% (95% CI, 4.0%-8.9%) in the dulaglutide group, corresponding to a risk difference of -0.2% (95% CI, -3.2% to 2.8%) and a risk ratio of 0.97 (95% CI, 0.59-1.61).</p><p><strong>Conclusions: </strong>This target trial emulation did not provide evidence for a substantial difference in cardiovascular outcomes between individuals with type 2 diabetes initiating semaglutide and dulaglutide.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 12","pages":"e70276"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668461","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":"Concurrent Alcohol Use and the Relative Risk of Community-Acquired Pneumonia Associated With Anticholinergic and Non-Anticholinergic Neurocognitively Active Medication Receipt: A National Nested Case-Control Study Among US Veterans.","authors":"William H Wang, Kristina Crothers, Kathleen M Akgün, Kirsha S Gordon, Maria C Rodriguez-Barradas, Julie A Womack, Jennifer Thompson, Amy C Justice, Christopher T Rentsch","doi":"10.1002/pds.70279","DOIUrl":"10.1002/pds.70279","url":null,"abstract":"<p><strong>Purpose: </strong>Anticholinergic medications and alcohol each independently increase the risk of community-acquired pneumonia (CAP). Whether non-anticholinergic neurocognitively active medications also increase risk, and if alcohol modifies these associations, remains unclear.</p><p><strong>Methods: </strong>We conducted a nested case-control study using Veterans Aging Cohort Study (VACS)-National data. We identified 157 185 incident CAP cases requiring hospitalization between 2010 and 2022. Cases were matched 1:5 to controls without CAP on demographics, cohort entry date, and dwell time in the underlying cohort study using incidence density (risk-set) sampling. CAP index date was hospital admission for cases and the equivalent follow-up date for controls. Primary exposures were receipt of anticholinergic and non-anticholinergic neurocognitively active medications within 90 days prior to the index date. Concurrent alcohol use was based on self-reported measures in the year prior to the index date. We estimated odds ratios (ORs) for associations between medication use, alcohol consumption, and CAP using logistic regression, adjusting for confounders.</p><p><strong>Results: </strong>Median age was 69 years (interquartile range 62-78); 97% were male. Both medication types were independently associated with increased odds of CAP (anticholinergic: OR 1.62, 95% CI 1.57-1.67; non-anticholinergic: OR 1.61, 95% CI 1.57-1.66). Concurrent alcohol use modified these associations. For anticholinergics, ORs were 1.74 (95% CI 1.66-1.83) for at-risk consumption and 2.13 (95% CI 1.96-2.31) for hazardous/binge consumption. For non-anticholinergics, ORs were 1.74 (95% CI 1.67-1.81) and 2.20 (95% CI 2.06-2.34), respectively.</p><p><strong>Conclusions: </strong>Non-anticholinergic neurocognitively active medications showed similar CAP association patterns as anticholinergics, with the highest odds among those consuming alcohol. These findings highlight the need for caution when prescribing these medications and incorporating alcohol use into risk-benefit assessments.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 12","pages":"e70279"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12676203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668549","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":"Risk of Major Congenital Malformations Associated With First-Trimester Exposure to Topical Antifungal Medications: A Large Claims Database Study.","authors":"Tadaharu Kunitoki, Takamasa Sakai, Tomofumi Ishikawa, Ryo Obara, Kei Morishita, Azusa Hara, Motohiko Adomi, Haruto Watanabe, Kaya Hayasaka, Yuna Yoshida, Aki Shimizu, Genki Shinoda, Aoi Noda, Mami Ishikuro, Masatsugu Orui, Noriyuki Iwama, Seiko Yamakoshi, Emiko Sato, Nariyasu Mano, Shinichi Kuriyama, Nobuyuki Takahashi, Taku Obara","doi":"10.1002/pds.70274","DOIUrl":"https://doi.org/10.1002/pds.70274","url":null,"abstract":"<p><strong>Purpose: </strong>Vulvovaginal candidiasis is highly prevalent among pregnant women, and its treatment is crucial. However, there is a lack of evidence regarding the risks on fetal outcomes associated with the use of antifungal medications during the first trimester of pregnancy in Japan. This study examined the association between topical antifungal use during the first trimester of pregnancy and the risk of major congenital malformations (MCMs) in infants using a Japanese database.</p><p><strong>Methods: </strong>We conducted a cohort study using a pregnancy cohort nested in the JMDC Claims Database from Japan. This dataset included 12 472 women who gave birth between 2010 and 2019 and were diagnosed with vulvovaginal candidiasis. Among the antifungal medications frequently dispensed or prescribed during the first trimester of pregnancy in this cohort, miconazole, oxiconazole, and isoconazole were assessed for the risk of MCMs, using clotrimazole, an antifungal medication with established safety during pregnancy, as a reference.</p><p><strong>Results: </strong>Among 12 472 women, the overall prevalence of MCMs was 5.8% (n = 249) in women exposed to topical antifungals, while unexposed were 6.2% (n = 508). Using propensity score overlap weight (wOR), no increased risk of MCMs in infants was observed in pregnancies exposed to oxiconazole, isoconazole, and miconazole compared to clotrimazole (overlap weighted odds ratio [95% confidence interval]: 0.875 [0.599-1.277], 1.001 [0.611-1.640], and 0.887 [0.497-1.581], respectively).</p><p><strong>Conclusion: </strong>There was no significant association between topical antifungal use during the first trimester of pregnancy and the risk of MCMs in infants in Japan.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 12","pages":"e70274"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687728","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":"Performance of the Self-Controlled Case Series With Active Comparators for Drug Safety Signal Detection Using the Clinical Practice Research Datalink (CPRD).","authors":"Astrid Coste, Angel Y S Wong, Francois Haguinet, Andrew Bate, Ian J Douglas","doi":"10.1002/pds.70243","DOIUrl":"10.1002/pds.70243","url":null,"abstract":"<p><strong>Background: </strong>There is little evidence about signal detection using UK primary care electronic health records (EHRs). The self controlled case series (SCCS) is one of the most promising methods for drug safety signal detection using real world data, and incorporating active comparators could potentially improve its performance by addressing confounding by indication.</p><p><strong>Objectives: </strong>This study aims to evaluate the performance of the SCCS with and without active comparators for signal detection using the UK Clinical Practice Research Datalink (CPRD) Aurum.</p><p><strong>Methods: </strong>We applied the SCCS to macrolide and fluoroquinolone antibiotics, using amoxicillin and cefalexin as active comparators. In total seven drugs, and 30 outcomes from all organ classes were selected. We developed a reference set of 104 positive controls and 58 negative controls, using a taxonomy framework to ensure the selected drug outcome pairs are theoretically well suited to the SCCS design. Two-year observation periods with a 30-day risk window after each dispensing were used. Diagnostic performance was measured using sensitivity and specificity with respect to the product labels.</p><p><strong>Results: </strong>The sensitivity and specificity of the SCCS without active comparator in the 2017/2018 observation period were 0.57 and 0.77 when limited to pairs with satisfactory power. Specificity increased up to 0.89 with active comparators, however sensitivity decreased to 0.18. Five drug-outcome pairs were signals of disproportionality before they were present on labels.</p><p><strong>Conclusions: </strong>Using a carefully designed reference set of drug-outcome pairs well suited to the study design, the SCCS performed moderately well for signal detection in CPRD. Whilst active comparators effectively reduced confounding by indication, they also reduced the number of correctly identified positive controls, due to a reduction in power. We showed some evidence that SCCS is able to highlight SDRs before they were present on labels.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 12","pages":"e70243"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12699507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743493","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}