Drug Safety最新文献

{"title":"The Frequency of Drug-Induced Liver Injury Due to Antibiotics Among Hospitalised Patients.","authors":"Robert A Björnsson, Sigurdur Sölvi Sigurdsson, Dagur Tjörvi Arnarson, Egill Logason, Einar Stefan Björnsson","doi":"10.1007/s40264-025-01541-w","DOIUrl":"10.1007/s40264-025-01541-w","url":null,"abstract":"<p><strong>Introduction: </strong>Most epidemiological studies have found antibiotics to be the most common cause of drug-induced liver injury (DILI). It is unclear what the risk of DILI is associated with different antibiotics.</p><p><strong>Objective: </strong>The aim of the study was to assess the frequency of DILI due to the most commonly used antibiotics among inpatients, in a population-based setting.</p><p><strong>Methods: </strong>Patients who were treated with the 14 most-used antibiotics at Landspitali University Hospital Iceland 2012-2023, with concomitant: > 5 × upper limit of normal (ULN) of alanine aminotransferase (ALT) and/or > 2 × ULN of alkaline phosphatase (ALP), were identified. If DILI was a potential cause, the Revised Electronic Causality Assessment Method (RECAM) method was used to determine likelihood of DILI.</p><p><strong>Results: </strong>Overall 2292 patients fulfilled the inclusion criteria, 52 of whom were found to have DILI, median age 67 (range 21-93) years, 58% females, 17 (33%) with jaundice and three (5.8%) died of liver failure. The most commonly implicated agent was amoxicillin/clavulanate (n = 23) in 1:1327 users (0.075%), ceftriaxone (n = 8) 1:3779 (0.02%), cefazolin (n = 7) 1: 6363 (0.016%), cloxacillin 1:6024 (n = 4) (0.017%), piperacillin/tazobactam (n = 2) 1:1551 (0.097%), vancomycin (n = 2) 1:1966 (0.076%), trimethoprim-sulfamethoxazole (TMP/SMX) (n = 3) 1:1096 (0.091%) and ciprofloxacin (n = 1) 1:10,938 (0.009%). In two cases, more than one antibiotic was considered likely.</p><p><strong>Conclusions: </strong>Drug-induced liver injury was found to be a rare adverse effect of antibiotics in a population-based setting. Overall, 33% presented with jaundice but three died of liver failure, all due to amoxicillin/clavulanate, which was the most common cause occurring in around 1 in 1300 users. However, TMP/SMX was associated with the highest proportional risk of DILI.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"795-804"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Narrative Search Engine for Case Series Assessment Supported by Artificial Intelligence Query Suggestions.","authors":"Alem Zekarias, Eva-Lisa Meldau, Shachi Bista, Joana Félix China, Lovisa Sandberg","doi":"10.1007/s40264-025-01529-6","DOIUrl":"10.1007/s40264-025-01529-6","url":null,"abstract":"<p><strong>Introduction: </strong>Manual identification of case narratives with specific relevant information can be challenging when working with large numbers of adverse event reports (case series). The process can be supported with a search engine, but building search queries often remains a manual task. Suggesting terms to add to the search query could support assessors in the identification of case narratives within a case series.</p><p><strong>Objective: </strong>The aim of this study is to explore the feasibility of identifying case narratives containing specific characteristics with a narrative search engine supported by artificial intelligence (AI) query suggestions.</p><p><strong>Methods: </strong>The narrative search engine uses Best Match 25 (BM25) and suggests additional query terms from two word embedding models providing English and biomedical words to a human in the loop. We calculated the percentage of relevant narratives retrieved by the system (recall) and the percentage of retrieved narratives relevant to the search (precision) on an evaluation dataset including narratives from VigiBase, the World Health Organization global database of adverse event reports for medicines and vaccines. Exact-match search and BM25 search with the Relevance Model (RM3), an alternative way to expand queries, were used as comparators.</p><p><strong>Results: </strong>The gold standard included 55/750 narratives labelled as relevant. Our narrative search engine retrieved on average 56.4% of the relevant narratives (recall), which is higher when compared with exact-match search (21.8%), without a significant drop in precision  (54.5% to 43.1%). The recall is also higher as compared with RM3 (34.4%).</p><p><strong>Conclusions: </strong>Our study demonstrates that a narrative search engine supported by AI query suggestions can be a viable alternative to an exact-match search and BM25 search with RM3, since it can facilitate the retrieval of additional relevant narratives during signal assessments.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"767-779"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on \"Drug-Induced Cognitive Impairment\".","authors":"Chaker Ben Salem","doi":"10.1007/s40264-025-01567-0","DOIUrl":"10.1007/s40264-025-01567-0","url":null,"abstract":"","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"839-840"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"REMS Logic Model: A Pragmatic Framework for Incorporating Drug Safety into Clinical Practice.","authors":"Gita A Toyserkani, Suzanne B Robottom, Elaine H Morrato","doi":"10.1007/s40264-025-01542-9","DOIUrl":"10.1007/s40264-025-01542-9","url":null,"abstract":"","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"715-718"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the Work of the Pharmacovigilance Risk Assessment Committee (PRAC): A Quantitative Review of the Post-Authorisation Safety Evaluation of Antidiabetic Drugs from 2012 to 2022.","authors":"Haoxin Le, Per Sindahl, Morten Andersen, Christine E Hallgreen","doi":"10.1007/s40264-025-01536-7","DOIUrl":"10.1007/s40264-025-01536-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The Pharmacovigilance Risk Assessment Committee (PRAC) plays a central role in the European Union's pharmacovigilance system, evaluating drug safety through several procedures and activities. Despite its central role, few studies have quantitatively investigated the PRAC's activities from a system's perspective.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aims to map PRAC's evaluation of safety signals and concerns using antidiabetic products as a case. It characterises the drugs and adverse events involved, analyses the PRAC-led regulatory procedures where the safety signals and concerns were evaluated, and provides a comprehensive review of PRAC meeting minutes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;From PRAC meeting minutes, we retrieved information on all antidiabetic drug-related adverse events discussed from 2012 to 2022. We identified drug-adverse event evaluations based on the discussion content. These were described by drug classes, System Organ Classes, PRAC procedures, and the evaluation outcomes corresponding to recommendations for regulatory actions. We also analysed the sequence of PRAC-led procedures and activities addressing drug-adverse event pairs across meeting minutes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 321 drug-adverse event pairs were identified, with 14 pairs associated with drug classes. Second-generation antidiabetic agents, including sodium-glucose transport protein-2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase 4 inhibitors, were the most frequently discussed. Of these, 62 pairs underwent multiple evaluations, resulting in a total of 413 evaluations. In 48% of evaluations, no regulatory action was required. Most evaluations (97%) were concluded in a single procedure, and 66% were concluded in one meeting. Periodic safety update reports accounted for 54% of drug-adverse event evaluations and updates to product information were the most frequent outcome. Signal assessment and prioritisation procedures, while less common, resulted in more diverse recommendations for regulatory action. Referrals were infrequent (N = 5) and were often triggered by the signal assessment and prioritisation procedure.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Periodic safety update reports are the primary source for PRAC evaluations of safety signals although they are not intended for notification of new urgent safety information. Compared with periodic safety update reports, the signal assessment and prioritisation procedure evaluates fewer signals but leads to a wider range of regulatory actions, from risk minimisation measures to referrals. This difference may be attributed to the fact that signals detected in periodic safety update reports are not intended for urgent safety issues, these should be assessed through the signal assessment and prioritisation procedure, as the latter involves real-time signal management, whereas the periodic safety update reports are conducted at pr","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"781-794"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Authors' reply to Chaker Ben Salem's comment on: \"Drug-Induced Cognitive Impairment\".","authors":"Arne Reimers, Per Odin, Hanna Ljung","doi":"10.1007/s40264-025-01568-z","DOIUrl":"10.1007/s40264-025-01568-z","url":null,"abstract":"","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"841"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of GLP1-Receptor Agonists with Risk of Hepatocellular Carcinoma: A Retrospective Cohort Study.","authors":"Joane Titus, Vinay Katukuri, Moheb Boktor, Ishak A Mansi","doi":"10.1007/s40264-025-01558-1","DOIUrl":"https://doi.org/10.1007/s40264-025-01558-1","url":null,"abstract":"<p><strong>Background: </strong>The use of glucagon-like peptide-1 receptor agonists (GLP-1RA) has exponentially increased owing to their favorable cardio-renal-metabolic effects. Some studies have raised concerns about a potential association between GLP-1RA use and malignancy. This study aimed to examine the association between GLP-1RA use and risk of hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>This retrospective propensity score (PS)-matched cohort study used data from the Veterans Health Administration (years 2006-2021). Using a new-user active comparator design, the study included adults who initiated a GLP-1RA or dipeptidyl peptidase-4 inhibitor (DPP4i) as an active comparator and had no prior history of HCC or liver transplantation. The primary outcome was incident HCC. We developed a PS that included 133 variables encompassing diabetes severity, hepatic conditions, liver disease scores, vital signs, laboratory investigations, comorbidity scores, and use of other medication classes.</p><p><strong>Results: </strong>Of 147,969 GLP-1RA and 263,664 DPP4i users, 100,248 pairs of GLP-1RA and DPP4i users were PS-matched. Hepatocellular carcinoma occurred in 302 (0.30%) GLP-1RA users and in 230 (0.23%) DPP4i users (odds ratio [OR]: 1.31, 95% confidence interval [95% CI]: 1.11-1.56). Secondary analysis, which stratified patients by duration of medication use, showed an increased risk of HCC in association with GLP-1RA use > 6 months, but similar HCC risk if medication use was < 6 months (OR: 0.96; 95% CI 0.68-1.35).</p><p><strong>Conclusions: </strong>Glucagon-like peptide-1 receptor agonists use was associated with a modest but statistically significant increase in HCC risk versus DPP4i use. Although the reported benefits of GLP-1RA seem to far exceed this modest increased risk, further studies are warranted due to exponentially increasing GLP-1RA use and their broadening indications.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of Drug-RElated Hospitalizations for Nursing HOme Residents: Cross-Sectional RENHO Study.","authors":"Alice Lopez, Chiara Alfarano, Marianne Lepetit, Leila Chebane, Nassima Redjimi, Anaïs Couret, Didier Fabre, Virginie Gardette, Driss Berdaï, Maryse Lapeyre-Mestre, Haleh Bagheri","doi":"10.1007/s40264-025-01556-3","DOIUrl":"https://doi.org/10.1007/s40264-025-01556-3","url":null,"abstract":"<p><strong>Background: </strong>Nursing home residents with advancing age are often exposed to polypharmacy, a well-known risk factor for adverse drug reactions (ADRs), which increases the risk of hospitalization. Therefore, we assessed the characteristics of and factors associated with ADR-related emergency department (ED) admissions among nursing home residents.</p><p><strong>Methods: </strong>We carried out a cross-sectional study using the Toulouse University Hospital discharge database to identify nursing home residents ED admissions from 1 April, 2019 to 31 March, 2020. Information was updated for 2 years after inclusion (re-admissions). Emergency department medical files were analyzed to identify factors associated with these admissions (including demographics, functional dependency level, comorbidities, body mass index, ED admission in the previous 12 previous months, and number of drugs).</p><p><strong>Results: </strong>We identified 1514 patients (corresponding to 2024 ED admissions), 409 of whom (27.0%) were admitted at least once for an ADR. Thirty-six nursing home residents were re-admitted in 2020 and/or 2021 for ADRs, half of whom were for the same ADR. The most frequent ADRs were falls (114, 24.3%), hemorrhagic events (106, 22.6%), and constipation (47, 10.0%) involving benzodiazepines and Z-drugs (170, 16.0%), antidepressants (125, 11.9%), antithrombotic drugs (110, 10.3%), and opioids (82, 7.7%). About 12% of ADRs were assessed as avoidable. Factors significantly associated with ADR-related ED admissions were the number of drugs (odds ratio 1.09; 95% confidence interval 1.05-1.13), previous ED admissions (odds ratio 3.47; 95% confidence interval 2.46-4.90), and overweight (odds ratio 1.54; confidence interval 1.15-2.06).</p><p><strong>Conclusions: </strong>Drug-induced iatrogenic disease could lead to ED admission for nursing home residents in approximately one-quarter of cases, 12% of which were assessed as avoidable. A previous history of ED admission and polypharmacy remain key associated factors. The awareness-raising campaigns for health professionals should be strengthened to prevent avoidable drug-induced ADRs.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal Trends of Anticholinergic Drug Exposure Among Older Adults: A 25-Year Population-Based Study.","authors":"Amanda Evelo, Silvan Licher, Bruno H Stricker, Loes E Visser, Rikje Ruiter","doi":"10.1007/s40264-025-01562-5","DOIUrl":"https://doi.org/10.1007/s40264-025-01562-5","url":null,"abstract":"<p><strong>Background: </strong>Exposure to anticholinergic drugs is associated with adverse outcomes, particularly among older adults. Limiting the anticholinergic burden (ACB) among older patients has been advocated for decades, but reliable population-level data on temporal trends are lacking. Here, we estimated the cumulative incidence and incidence rates (IRs) of a cumulative ACB score of three or more (cACB ≥ 3) among older adults in a community-dwelling population and described the changes in IR over the past 25 years.</p><p><strong>Methods: </strong>Within the population-based Rotterdam Study, pharmacy dispensing records were obtained from 11,038 individuals aged 65+ years from 1996 to 2020. The cACB score was calculated with the Anticholinergic Cognitive Burden Scale and supplemented with drugs on the ACB scale by the Expertisecentre PHarmacotherapy in OldeR people (EPHOR). Age- and sex-specific IRs were calculated, and non-overlapping 5-year episodes were defined to determine time trends in IRs.</p><p><strong>Results: </strong>The cumulative incidence of a cACB ≥ 3 was 25.3% between 1996 and 2020. Compared with 1996-2000, the IR of cACB ≥ 3 had declined by 54% between the 2016-2022 episode (IR ratio: 0.46, 95% confidence interval (CI): 0.41-0.52). Participants aged 86-90 years had more than 1.5 times the rate of a cACB ≥ 3 compared with participants aged 66-70 years (IR ratio: 1.67, 95% CI 1.46-1.91).</p><p><strong>Conclusions: </strong>Exposure to anticholinergic drugs has decreased by over 50% between 1996 and 2020 in this population of community-dwelling adults. However, the oldest old had and remained to have the highest risk of a cACB ≥ 3 during our study period. Thus, prescribers and pharmacists should continue to regularly review the prescription of drugs with an ACB, especially among those vulnerable to adverse outcomes.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex Differences in Electrolyte Disturbances Among Diuretic Users According to Renal Function and Age.","authors":"Narumi Maida, Shingo Kondo, Naoko Hayashi, Hiroki Iwata, Noriko Kobayashi, Katsunori Yamaura","doi":"10.1007/s40264-025-01564-3","DOIUrl":"https://doi.org/10.1007/s40264-025-01564-3","url":null,"abstract":"<p><strong>Introduction: </strong>Diuretics are widely used in Japan for the treatment of hypertension and heart failure. Electrolyte disturbance is a common adverse reaction to diuretics and may be life-threatening. Previous studies have shown that diuretic-induced electrolyte disturbance is more common in women. Electrolyte balance is regulated by the kidneys, and renal function tends to decline with advancing age.</p><p><strong>Objective: </strong>The aim of this study was to identify patients at high risk of adverse reactions to diuretics, considering the effects of sex, renal function, and age on susceptibility to diuretic-induced electrolyte disturbance.</p><p><strong>Methods: </strong>Claims data for 67,135 patients on diuretics in Japan were sourced from DeSC Healthcare, Inc. The data covered the period from April 2020 to March 2021.</p><p><strong>Results: </strong>Analysis of patient numbers using the chi-squared test showed that hyperkalemia was more common in men than in women (326 vs. 271; p = 0.003) and that hypokalemia was more common in women than in men (413 vs. 285; p < 0.001). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for women considering age and renal function (estimated glomerular filtration rate [eGFR]). In elderly patients aged ≥ 75 years, the odds of developing hypokalemia in women compared to men were 1.47 (95% CI 1.13-1.91) for eGFR 60-30 mL/min/1.73 m² and 2.05 (95% CI 1.08-4.10) for eGFR < 30 mL/min/1.73 m².</p><p><strong>Conclusion: </strong>Among women aged ≥ 75 years, those in lower eGFR groups (60-30 and < 30) had higher odds of hypokalemia compared to men. These data highlight the importance of monitoring for adverse reactions to diuretics, particularly hypokalemia, in elderly women with low eGFR.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}