Therapeutic Advances in Drug Safety最新文献

{"title":"Machine learning studies of drug-induced nephrotoxicity: a scoping review.","authors":"Mawardi Ihsan, Shu-Ting Chang, Wei-Kai Chan, Hsiang-Yin Chen","doi":"10.1177/20420986261430234","DOIUrl":"10.1177/20420986261430234","url":null,"abstract":"<p><strong>Background: </strong>Machine learning methods have emerged as a promising approach to prevent drug-induced nephrotoxicity.</p><p><strong>Objective: </strong>This review evaluates the quality and highlights recent advances of machine learning algorithms for predicting drug-induced nephrotoxicity.</p><p><strong>Eligibility criteria: </strong>Studies on machine learning models to predict drug-induced acute kidney injury, acute kidney disease, or both published between January 2014 and August 2024 were eligible.</p><p><strong>Sources of evidence: </strong>A comprehensive search was conducted by using PubMed, Embase, Web of Science, Cochrane Library, and Scopus.</p><p><strong>Charting methods: </strong>A standardized charting form was developed based on CHARMS, TRIPOD+AI, and PROBAST tools to assess the quality and risk of bias across studies.</p><p><strong>Results: </strong>From the initial 5,179 articles searched, 24 studies were included in this review. All studies achieved good area under the receiver operating characteristic curves (AUROCs) above 0.75, with boosting machines being the most frequently outperforming algorithms (<i>n</i> = 7, 29.17%), and neural networks showed the highest median AUROC of 0.90 (0.86-0.92). Two-thirds of studies (<i>n</i> = 16; 66.67%) predicted acute kidney injury, whereas only 5 (20.83%) focused on acute kidney disease. Estimated glomerular filtration rate, blood urea nitrogen, serum creatinine, hemoglobin, and albumin emerged as the most utilized features by 10 (41.67%), 9 (37.5%), 9 (37.5%), 8 (33.33%), and 8 (33.33%) studies, respectively. Diabetes, heart failure, diuretics, and non-steroidal anti-inflammatory drugs were frequently selected features by 7 (29.17%), 5 (20.83%), 5 (20.83%), and 4 (16.67%) studies, respectively. The 2025 PROBAST+AI risk-of-bias assessment indicated that 7 (29.17%) studies had a low risk of bias. A high risk of bias was observed in 20 (83.33%), 18 (75%), and 17 (70.83%) studies due to insufficient performance evaluation, small sample sizes, and lack of external validation.</p><p><strong>Conclusion: </strong>Recent machine learning studies have demonstrated great performance using clinically obtainable features. Incorporating acute kidney injury and disease, methodological enhancement, and guideline adherence can facilitate clinical applicability in preventing drug-induced nephrotoxicity.</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"17 ","pages":"20420986261430234"},"PeriodicalIF":3.4,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147514984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of ciprofol versus propofol for sedation in hysteroscopy: a systematic review and meta-analysis.","authors":"Zoha Anwar, Hafsa Ahsun, Taha Iqbal, Muhammad Saad Khan, Sarah Rehan, Areej Fatima, Fawad Sarwar, Hafsa Haseen, Umaimah Naeem, Kalpana Singh, Aminath Waafira","doi":"10.1177/20420986261427077","DOIUrl":"10.1177/20420986261427077","url":null,"abstract":"<p><strong>Background: </strong>Hysteroscopy, a popular outpatient gynecological procedure, often requires sedation due to pain caused by endometrial manipulation and cervical dilation. Propofol, the current standard sedative, has adverse effects like respiratory depression, hypotension, and injection discomfort. Ciprofol, a novel GABA-A receptor agonist and structural analog of propofol, might be a safer choice while maintaining efficacy.</p><p><strong>Objectives: </strong>This systematic review and meta-analysis aims to compare the efficacy and safety of ciprofol versus propofol for sedation during hysteroscopy.</p><p><strong>Design: </strong>A systematic review and meta-analysis of randomized controlled trials (RCTs).</p><p><strong>Data sources and methods: </strong>This systematic review and meta-analysis adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RCTs comparing ciprofol and propofol for hysteroscopic sedation were sourced from PubMed, Cochrane, Scopus, Google Scholar, and ClinicalTrials.gov. Data extraction, quality assessment (ROB-2), and analysis were conducted independently. Outcomes included efficacy, safety, and recovery metrics.</p><p><strong>Results: </strong>Six RCTs with 1890 patients were met with inclusion. Ciprofol achieved similar sedative success as propofol (risk ratio (RR) = 1.00, 95% CI: 1.00-1.00) and surpassed propofol in important safety outcomes. It significantly reduced intraoperative body movements (RR = 0.53), injection pain (RR = 0.13), hypotension (RR = 0.58), and respiratory depression (RR = 0.67), while increasing eyelash reflex suppression (MD = 0.24). Ciprofol was also associated with a slightly longer recovery time compared to propofol (MD = 0.80 min). Bradycardia incidence and procedure duration did not differ significantly.</p><p><strong>Conclusion: </strong>Ciprofol displays a better safety profile, including enhanced hemodynamic and respiratory stability and decreased injection discomfort, and is just as effective as propofol for sedation during hysteroscopy. According to these results, ciprofol is a safe alternative to propofol for hysteroscopy. It is advised that further multicenter studies are required to confirm its effectiveness across broader populations.</p><p><strong>Trial registration: </strong>The meta-analysis has been registered with PROSPERO. The registration number is CRD420251091116.</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"17 ","pages":"20420986261427077"},"PeriodicalIF":3.4,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin-associated lactic acidosis in an elderly diabetic patient without classical risk factors: a case report.","authors":"Yali Zheng, Jia Sun, Peng Zhang, Quanfeng Zhu","doi":"10.1177/20420986261428996","DOIUrl":"https://doi.org/10.1177/20420986261428996","url":null,"abstract":"<p><p>Metformin is a cornerstone medication and first-line therapy for type 2 diabetes mellitus (T2DM), with a well-established safety profile and widespread use over many years. Its most common adverse effects are gastrointestinal in nature. However, the drug carries a rare but serious risk of lactic acidosis. Recognized risk factors for metformin-associated lactic acidosis (MALA) include renal or hepatic impairment, excessive alcohol consumption, poorly controlled diabetes, ketosis, prolonged fasting, and conditions predisposing to hypoxia. This paper presents a case of MALA in a 75-year-old patient with T2DM and schizophrenia who lacked any typical risk factors. This case underscores the importance of maintaining a high index of suspicion for this potentially fatal complication in all patients taking metformin. Early recognition and prompt intervention are critical to improving clinical outcomes.</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"17 ","pages":"20420986261428996"},"PeriodicalIF":3.4,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The magnitude of drug-related problems, typology, and predictors among patients admitted to the pediatric intensive care unit: impact of pharmacist-led interventions in Northwest Ethiopia.","authors":"Abel Temeche Kassaw, Getachew Yitayew Tarekegn, Tigabu Eskeziya Zerihun, Abaynesh Fentahun Bekalu, Samuel Agegnew Wondm, Tilaye Arega Moges, Woretaw Sisay Zewdu, Fasil Bayafers Tamene, Desalegn Addis Mussie, Samuel Berihun Dagnew","doi":"10.1177/20420986261422800","DOIUrl":"https://doi.org/10.1177/20420986261422800","url":null,"abstract":"<p><strong>Background: </strong>Drug-related problems (DRPs) are a significant concern in hospitalized patients. In Ethiopia, DRPs occur at a rate of 9.2 per 100 admissions and 9.4 per 1,000 patient days; however, pediatric-specific data are limited.</p><p><strong>Objective: </strong>This study assessed the magnitude, types, and predictors of DRPs and evaluated the acceptability of pharmacist-led interventions in pediatric intensive care units (PICUs) in Northwest Ethiopia.</p><p><strong>Design: </strong>A multicenter prospective interventional study.</p><p><strong>Methods: </strong>All pediatric patients admitted to the PICU during the study period were consecutively enrolled. The study was conducted from January 1, 2025 to March 31, 2025 across four specialized hospitals, resulting in a total of 394 participants. DRPs were identified through medical record reviews, caregiver interviews, and direct bedside assessment by a clinical pharmacist. Each DRP was classified according to the Pharmaceutical Care Network Europe (PCNE) classification system version 8.01. Binary logistic regression was performed to identify independent predictors of DRPs.</p><p><strong>Results: </strong>Of the patients, 251 (63.7%) experienced at least one DRP, with 522 DRPs identified (mean 1.3 ± 0.8 per patient). The dominant domains were treatment effectiveness (54.6%) and treatment safety (30.3%), and 97.7% were deemed preventable. Drug and dose selection were the main causes (46.0% and 43.8%, respectively). Independent predictors included age 29 days-1 year (AOR = 2.2, 95% CI: 1.0-4.8), polypharmacy (⩾5 medications; AOR = 1.7, 95% CI: 1.0-2.8), multiple prescribers (AOR = 1.8, 95% CI: 1.1-2.9), prolonged ICU stay (⩾10 days; AOR = 2.4, 95%CI: 1.2-4.7), circulatory system disease (AOR = 3.5, 95% CI: 1.4-9.0), the use of anti-infectives (AOR = 5.0, 95% CI: 2.0-13.7), and antiepileptics medications (AOR = 2.1, 95% CI: 1.0-4.3) were independent predictors of DRPs.</p><p><strong>Conclusion: </strong>DRPs were common in PICU but predominantly preventable. Despite a modest mean number of DRPs per patient, the type and causes identified indicate opportunities for optimizing medication use. Younger age, polypharmacy, multiple prescribers, prolonged PICU stays, circulatory system disease, and specific drug classes were independent predictors. The high acceptance and effectiveness of pharmacist-led interventions underscore their crucial role in improving medication safety and optimizing pharmacotherapy in resource-limited intensive care settings.</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"17 ","pages":"20420986261422800"},"PeriodicalIF":3.4,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12923928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disparities and trends in drug-related adverse reaction mortality in the United States, 1999-2020.","authors":"Liwei Guo, Xiuxun Dong","doi":"10.1177/20420986261421278","DOIUrl":"10.1177/20420986261421278","url":null,"abstract":"<p><strong>Background: </strong>Adverse drug reactions (ADRs) are a leading cause of morbidity and mortality worldwide. Despite advances in pharmacovigilance, population-level evidence on long-term trends and disparities in ADR-related mortality in the United States remains limited.</p><p><strong>Objectives: </strong>This study aimed to characterize national temporal trends and demographic, geographic, and drug-class disparities in ADR-related mortality.</p><p><strong>Design: </strong>Population-based, cross-sectional analysis of US death certificate data using age-adjusted mortality rates (AAMRs) and log-linear estimated annual percentage changes (EAPCs) to assess temporal trends.</p><p><strong>Methods: </strong>ADR-related deaths were identified using International Classification of Diseases, Tenth Revision (ICD-10) codes Y40-Y59. AAMRs and EAPCs were calculated to assess temporal trends. Frontier analysis evaluated the relationship between AAMR and the Socio-Demographic Index (SDI) across states, and the leading drug categories contributing to ADR-related deaths were identified.</p><p><strong>Results: </strong>A total of 8425 ADR-related deaths were recorded over the study period. The national AAMR increased from 0.086 per 100,000 in 1999 to 0.140 in 2020 (EAPC: 1.49). Men, older adults, Black individuals, and rural residents experienced disproportionately high AAMRs. The West and Midwest regions exhibited steeper increases than other regions. Frontier analysis identified high-SDI states performing comparatively better. Among specific drug classes, anticoagulants were the leading contributors to ADR-related deaths, followed by immunosuppressive agents, antineoplastic drugs, and opioids.</p><p><strong>Conclusion: </strong>ADR-related mortality in the United States rose steadily, with pronounced disparities by sex, age, race, geography, and rurality. These findings should be interpreted with caution, given the observational study design and reliance on death certificate-based data.</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"17 ","pages":"20420986261421278"},"PeriodicalIF":3.4,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12905101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Donor and recipient genetic polymorphisms modulate tacrolimus pharmacokinetics during voriconazole co-therapy: a drug-drug interaction study in liver transplant recipients.","authors":"Jieling Li, Liubing Li, Yanzhe Xia, Jie Chen, Jiali Li, Xiaobin Lin, Xiao Chen, Ke-Jing Tang, Pan Chen, Xiaoman Liu","doi":"10.1177/20420986261420282","DOIUrl":"10.1177/20420986261420282","url":null,"abstract":"<p><strong>Background: </strong>While recipient cytochrome P450 (CYP) genetic polymorphisms are established modulators of tacrolimus (TAC) pharmacokinetics, the combined effects of donor-derived hepatic and recipient intestinal <i>CYP3A4/5</i> and <i>CYP2C19</i> genotypes during voriconazole (VRC)-mediated CYP3A inhibition remain inadequately elucidated in liver transplantation.</p><p><strong>Objectives: </strong>This study evaluated the impact of donor and recipient <i>CYP3A4/5</i> and <i>CYP2C19</i> polymorphisms on TAC pharmacokinetics during VRC co-therapy in liver transplant recipients.</p><p><strong>Design: </strong>A retrospective study was conducted on 139 liver transplant patients receiving TAC-based immunosuppressive therapy at the First Affiliated Hospital of Sun Yat-sen University from December 2016 to June 2025.</p><p><strong>Methods: </strong>The liver transplant recipients were stratified into a VRC co-therapy group (<i>n</i> = 33) and a non-VRC control group (<i>n</i> = 106). TAC dose-corrected trough concentrations (C₀/D) were analyzed in relation to donor and recipient genotypes of <i>CYP3A4*1G</i> (rs2242480), <i>CYP3A5*3</i> (rs776746), <i>CYP2C19*2</i> (rs4244285), and <i>CYP2C19*3</i> (rs4986893).</p><p><strong>Results: </strong>During VRC co-therapy, dual donor-recipient <i>CYP3A4*1G</i> CC carriers exhibited a 73% increase in TAC C₀/D compared with TT/TC genotypes (6.83 vs 3.95, <i>p</i> = 0.0031). Recipients grafted from CYP3A5 non-expresser donors exhibited 34% higher TAC C₀/D than those from CYP3A5 expressers (6.35 vs 4.75, <i>p</i> = 0.0196). Recipient CYP2C19 poor metabolizers demonstrated 36% elevated TAC C₀/D compared to extensive or intermediate metabolizers (6.47 vs 4.76, <i>p</i> = 0.0401). The magnitude of TAC-VRC interaction was modulated by both donor and recipient genotypes. Comparing with the control group, VRC co-therapy increased TAC C₀/D by 3.80- and 2.75-fold increases in CYP3A5 expresser and non-expresser recipients, respectively, and by 3.44- and 3.53-fold in recipients grafted from CYP3A5 expresser and non-expresser donors, respectively. Post-VRC discontinuation, TAC C₀/D remained significantly elevated for 5 days before returning to baseline level by day 6 (<i>p</i> < 0.0001).</p><p><strong>Conclusion: </strong>In summary, Donor and recipient <i>CYP3A4/5</i> and <i>CYP2C19</i> genotypes jointly influence TAC pharmacokinetics during VRC co-therapy. Genotype-guided dosing strategies integrating both donor and recipient genotypes may improve TAC dosing precision. TAC dose reinstatement may be deferred until day six following VRC discontinuation to avoid overexposure.</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"17 ","pages":"20420986261420282"},"PeriodicalIF":3.4,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12901897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges and future perspectives of enhanced passive safety surveillance of influenza vaccines in Europe.","authors":"Marina Amaral de Avila Machado, Sonja Gandhi-Banga, Laurence Serradell, Sophie Gallo, Sophie Wagué, Tamala Mallett Moore, Alena Khromava","doi":"10.1177/20420986261416017","DOIUrl":"10.1177/20420986261416017","url":null,"abstract":"<p><p>Postmarketing surveillance is critical for confirming the safety profile of vaccines following regulatory approval. This article contributes to the ongoing discussion on safety surveillance strategies for seasonal influenza vaccines in Europe. We examine the implementation of enhanced passive safety surveillance (EPSS) for seasonal influenza vaccines from season 2015/16 through season 2023/24, as conducted by a Marketing Authorization Holder in accordance with European Medicines Agency guidelines. We describe the evolution of data collection methods of EPSS studies conducted across nine seasons in Finland, United Kingdom, Republic of Ireland, Denmark, and Germany with different influenza vaccine formulations. Exposure data were prospectively collected in vaccination cards at the time of vaccination, while safety data collection evolved from telephone calls to electronic reporting systems. The use of an electronic system in recent seasons facilitated adverse drug reaction reporting by the vaccinees and improved real-time monitoring and accurate data collection. Operational challenges included country and site selection constraints and difficulty achieving target sample sizes and age group representation within short recruitment windows. Reporting rates varied across seasons, countries, and vaccine formulations, potentially influenced by factors such as vaccine reactogenicity, population demographics, and reporting behaviors. Future perspectives suggest the need for a unified Europe-wide safety surveillance system to enhance collaboration among regulatory bodies, public health agencies, and vaccine manufacturers, ultimately contributing to a more robust and reliable safety framework for influenza vaccines.</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"17 ","pages":"20420986261416017"},"PeriodicalIF":3.4,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12858733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146107410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How is AI developing in pharmacovigilance?","authors":"Andrew Bate, Philip Michael Tregunno","doi":"10.1177/20420986251412773","DOIUrl":"10.1177/20420986251412773","url":null,"abstract":"","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"17 ","pages":"20420986251412773"},"PeriodicalIF":3.4,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12858747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146107376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the patterns of use and safety of lenalidomide treatment in myelodysplastic syndromes: a European, observational multi-registry study.","authors":"Iris Kim, Aidan Makwana, Victoria Ezenma, Stefania Navarcikova, Muskan Mittal, Quinn Ho, Hannah Borda, Stefan Kaehler","doi":"10.1177/20420986251407181","DOIUrl":"10.1177/20420986251407181","url":null,"abstract":"<p><strong>Background: </strong>Lenalidomide is an immunomodulatory agent thought to inhibit the growth of del(5q) haematopoietic progenitors in myelodysplastic syndromes (MDS) that was approved for use in Europe for certain forms of these conditions in 2013.</p><p><strong>Objectives: </strong>This study aimed to identify the distribution of lenalidomide treatment and safety outcomes in patients with MDS in Europe among those treated within (on-label) and outside (off-label) of the European Commission-approved indication.</p><p><strong>Design: </strong>This observational, retrospective study of prospectively collected disease registry data (13 June 2013 to 1 May 2023) summarised lenalidomide treatment patterns and safety outcomes by on- and off-label treatment in 11 European countries.</p><p><strong>Methods: </strong>Safety outcomes included progression to acute myeloid leukaemia (AML), second primary malignancies (SPMs), adverse events (AEs) and all-cause mortality. Hazard ratios (HRs) and 95% CI were reported for progression to AML comparing on- to off-label treatment.</p><p><strong>Results: </strong>Among 523 qualifying patients, more were prescribed lenalidomide off-label (<i>n</i> = 345) than on-label (<i>n</i> = 157); label status was unknown in 21 patients prescribed lenalidomide. Progression to AML occurred in 10.2% of on-label patients and 13.0% of off-label patients (HR: 0.9; 95% CI: 0.4, 1.7). Solid tumours were the most common SPM (7.0% on-label, 1.7% off-label). Neutropenia (38.9% on-label, 33.3% off-label) and thrombocytopenia (36.9% on-label, 28.1% off-label) were the most common AEs. Death occurred in 53 on-label and 75 off-label patients. The most common causes of death were unknown (19.1% on-label, 4.3% off-label) or due to AML (3.2% on-label, 6.1% off-label).</p><p><strong>Conclusion: </strong>Analysis of real-world registry data indicated that off-label lenalidomide use in patients treated for MDS was common. Across the registries studied, the overall incidence of safety events of lenalidomide in patients with MDS was consistent in both on-label and off-label use, highlighting the importance of researching off-label use of lenalidomide in MDS.</p><p><strong>Trial registration: </strong>This study was registered with the EU Post-Authorisation Studies (PAS) Register: EUPAS22604.</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"17 ","pages":"20420986251407181"},"PeriodicalIF":3.4,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12847667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146087119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug-induced intestinal obstruction: insights from the FDA Adverse Event Reporting System.","authors":"He Li, Yingjie Li, Lu Liu, Bing Zeng, Sihui Su, Jianjian Liu, Chun Pan, Tianlong Li","doi":"10.1177/20420986251414836","DOIUrl":"https://doi.org/10.1177/20420986251414836","url":null,"abstract":"<p><strong>Background: </strong>Intestinal obstruction is a severe abdominal condition that can be triggered by various medications; however, the drugs most strongly and frequently linked to this adverse event (AE) remain insufficiently defined in the current medical literature.</p><p><strong>Objectives: </strong>This study sought to systematically identify and evaluate medications most strongly and consistently associated with intestinal obstruction by analyzing real-world evidence from a large pharmacovigilance database.</p><p><strong>Design: </strong>We conducted a retrospective, observational pharmacovigilance study.</p><p><strong>Methods: </strong>Reports submitted to the U.S. FDA Adverse Event Reporting System (FAERS) between January 2004 and June 2024 were analyzed. Disproportionality analyses using the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Empirical Bayesian Geometric Mean, and Information Component were conducted to identify significant safety signals associated with drug-induced intestinal obstruction.</p><p><strong>Results: </strong>Among 21,433,114 AE reports, 60,814 (0.28%) involved intestinal obstruction. Humira (10,356 cases) was the most frequently reported drug, followed by Remicade (2223 cases), Avastin (1580 cases), Vedolizumab (1385 cases), Clozaril (1229 cases), and Accutane (1088 cases). Disproportionality analysis revealed that the top five drugs with the highest ROR and PRR were Accutane, Teduglutide, Lonsurf, Avastin, and Lynparza. Among the top 50 drugs, 47 lacked clear labeling in their drug packaging.</p><p><strong>Conclusion: </strong>Our findings, derived from FAERS signal detection, identify drug-event pairs that warrant further clinical evaluation. These results should not be interpreted as evidence of causality. The high volume of reports associated with certain drugs may reflect usage patterns, underlying disease conditions, or reporting behaviors. Caution should be exercised in clinical translation.</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"17 ","pages":"20420986251414836"},"PeriodicalIF":3.4,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12835516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146094224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}