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Atypical femoral fracture (AFF) is a rare complication related to the use of bisphosphonates (BPs). Herein, we analyzed the risk factors and onset patterns of AFF using the Japanese Adverse Drug Event Report database and reported the findings. First, the independent risk factors for AFF were gender (female), high body mass index, and medical history of osteoporosis, arthritis, and systemic lupus erythematosus (SLE). Drug-related risk factors for AFF included BPs (i.e., alendronic acid, ibandronic acid, etidronic acid, zoledronic acid, minodronic acid, risedronic acid), denosumab, prednisolone, lansoprazole, rabeprazole, exemestane, letrozole, eldecalcitol, and menatetrenone. Therefore, it appears that AFF is influenced by a combination of patient backgrounds and drugs, and that the risk of developing AFF is particularly high in patients with fragile bones (e.g., osteoporosis, arthritis, and SLE). Second, in the analysis of AFF onset patterns, the onset of AFF from BPs and denosumab took a long time (>1 year) to develop. Analysis using a Weibull distribution showed wear-out failure-type AFF onset for BPs and denosumab, and both osteoporosis and cancer patients with long-term administration of these drugs showed a tendency to have an increased risk of onset. AFF developed earlier in osteoporosis patients with long-term administration of BPs and denosumab than in cancer patients.

Background: Although some sepsis cases were reported with immune checkpoint inhibitors (ICIs) in clinical trials, the link between pulmonary sepsis and ICIs remains mostly unknown. We aim to investigate the association between pulmonary sepsis and ICIs, and to describe the clinical features. Methods: A disproportionality analysis was performed using FAERS data and compared rates of pulmonary sepsis in cancer patients receiving ICIs vs. other drug regimens (such as chemotherapy and targeted therapy). Associations between ICIs and sepsis were assessed using reporting odds ratios (ROR) and information component (IC). We also detected drug interaction signals based on the Ω shrinkage measure. Age and gender distribution were compared between pulmonary sepsis and all adverse events associated with ICIs. Results: We identified 120 reports of pulmonary sepsis associated with ICIs between Q1, 2011 to Q3, 2021. A total of 82 of 120 (68.3%) patients on ICIs suffered from pulmonary sepsis and progressed to death. In addition, there is no significant difference in age and gender in the occurrence of pulmonary sepsis in cancer patients on ICIs. Overall ICIs, nivolumab, and atezolizumab still have a significant signal of pulmonary sepsis (ROR025 > 1, IC025 > 0, p < 0.001) compared with targeted therapy (such as tyrosine kinase inhibitors) or chemotherapy. Co-administration of ICIs and glucocorticoids or proton pump inhibitors synergistically increased the risk of pulmonary sepsis (Ω025 > 0). Conclusions: Our study suggested ICIs, especially nivolumab and atezolizumab, tended to increase the risk of pulmonary sepsis more than other anticancer regimens. Clinicians should be vigilant in the prevention and management of pulmonary sepsis during ICIs therapy.

BackgroundMosunetuzumab is a CD20×CD3 bispecific antibody approved for adult relapsed or refractory follicular lymphoma. Post-marketing evidence on its safety profile remains scarce. This pharmacovigilance study used the Food and Drug Administration Adverse Event Reporting System (FAERS)to characterize real-world adverse event (AE) signals associated with mosunetuzumab.MethodsWe performed disproportionality analysis using reports from the FAERS database spanning from the first quarter of 2004 to the fourth quarter of 2025. The primary analysis set encompassed reports wherein mosunetuzumab was coded as the Primary Suspect (PS). Disproportionality analyses were performed using four algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma poisson shrinker (MGPS). After excluding implausible records, the time to onset (TTO)for AEs was summarized using the median and interquartile range.ResultsOverall, 1154 FAERS reports mentioning mosunetuzumab were included in the primary analysis. 3 positive signals were identified at the System Organ Class (SOC)level. Cytokine release syndrome (CRS), neutropenia, tumour flare and infection-related events were frequently reported signals at the Preferred Term (PT)level. Additional disproportionate reporting signals were noted for cardiac events and eye disorders, including atrial fibrillation, uveitis. Of 310 reports with valid dates, most AEs occurred within 30 days following treatment initiation, whereas a nontrivial proportion was reported at ≥180 days.ConclusionThis study offers real-world evidence for guiding the clinical use of mosunetuzumab. It highlights the necessity for clinicians to monitor for AEs during treatment by recognizing potential adverse reaction signals beyond those documented in the current prescribing information.

Background: Metformin had been recommended as the first-line treatment for type 2 diabetes since 2006 because of its low cost, high efficacy, and potential to reduce cardiovascular events, and thus death. However, dipeptidyl peptidase-4 (DPP-4) inhibitors are the most commonly prescribed first-line agents for patients with type 2 diabetes in Japan. Therefore, it is necessary to clarify the effect of DPP-4 inhibitors on preventing cardiovascular events, taking into consideration the actual prescription of antidiabetic drugs in Japan. Methods: This study examined the effect of DPP-4 inhibitors on preventing cardiovascular events. The Japanese Adverse Drug Event Report (JADER) database, a spontaneous reporting system in Japan, and the Japanese Medical Data Center (JMDC) Claims Database, a Japanese health insurance claims and medical checkup database, were used for the analysis. Metformin was used as the DPP-4 inhibitor comparator. Major cardiovascular events were set as the primary endpoint. Results: In the analysis using the JADER database, a signal of major cardiovascular events was detected with DPP-4 inhibitors (IC: 0.22, 95% confidence interval: 0.03–0.40) but not with metformin. In the analysis using the JMDC Claims Database, the hazard ratio of major cardiovascular events for DPP-4 inhibitors versus metformin was 1.01 (95% CI: 0.84–1.20). Conclusions: A comprehensive analysis using two different databases in Japan, the JADER and the JMDC Claims Database, showed that DPP-4 inhibitors, which are widely used in Japan, have a non-inferior risk of cardiovascular events compared to metformin, which is used as the first-line drug in the United States and Europe.

In pharmacovigilance, disproportionality analyses based on individual case safety reports are widely used to detect safety signals. Unfortunately, publishing disproportionality analyses lacks specific guidelines, often leading to incomplete and ambiguous reporting, and carries the risk of incorrect conclusions when data are not placed in the correct context. The REporting of A Disproportionality analysis for drUg Safety signal detection using individual case safety reports in PharmacoVigilance (READUS-PV) statement was developed to address this issue by promoting transparent and comprehensive reporting of disproportionality studies. While the statement paper explains in greater detail the procedure followed to develop these guidelines, with this explanation paper we present the 14 items retained for READUS-PV guidelines, together with an in-depth explanation of their rationale and bullet points to illustrate their practical implementation. Our primary objective is to foster the adoption of the READUS-PV guidelines among authors, editors, peer reviewers, and readers of disproportionality analyses. Enhancing transparency, completeness, and accuracy of reporting, as well as proper interpretation of their results, READUS-PV guidelines will ultimately facilitate evidence-based decision making in pharmacovigilance.

Background and aim Disproportionality analyses using reports of suspected adverse drug reactions are the most commonly used quantitative methods for detecting safety signals in pharmacovigilance. However, their methods and results are generally poorly reported in published articles and existing guidelines do not capture the specific features of disproportionality analyses. We here describe the development of a guideline (REporting of A Disproportionality analysis for drUg Safety signal detection using individual case safety reports in PharmacoVigilance [READUS-PV]) for reporting the results of disproportionality analyses in articles and abstracts. Methods We established a group of 34 international experts from universities, the pharmaceutical industry, and regulatory agencies, with expertise in pharmacovigilance, disproportionality analyses, and assessment of safety signals. We followed a three-step process to develop the checklist: (1) an open-text survey to generate a first list of items; (2) an online Delphi method to select and rephrase the most important items; (3) a final online consensus meeting. Results Among the panel members, 33 experts responded to round 1 and 30 to round 2 of the Delphi and 25 participated to the consensus meeting. Overall, 60 recommendations for the main body of the manuscript and 13 recommendations for the abstracts were retained by participants after the Delphi method. After merging of some items together and the online consensus meeting, the READUS-PV guidelines comprise a checklist of 32 recommendations, in 14 items, for the reporting of disproportionality analyses in the main body text and four items, comprising 12 recommendations, for abstracts. Conclusions The READUS-PV guidelines will support authors, editors, peer-reviewers, and users of disproportionality analyses using individual case safety report databases. Adopting these guidelines will lead to more transparent, comprehensive, and accurate reporting and interpretation of disproportionality analyses, facilitating the integration with other sources of evidence.

Introduction: Linezolid is an oxazolidinone antibiotic that is active against drug-resistant Gram-positive bacteria and multidrug-resistant Mycobacterium tuberculosis . Real-world studies on the safety of linezolid in large populations are lacking. This study aimed to determine the adverse events associated with linezolid in real-world settings by analyzing data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Methods: We retrospectively extracted reports on adverse drug events (ADEs) from the FAERS database from the first quarter of 2004 to that of 2023. By using disproportionality analysis including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), along with the multi-item gamma Poisson shrinker (MGPS), we evaluated whether there was a significant association between linezolid and ADE. The time to onset of ADE was further analyzed in the general population and within each age, weight, reporting population, and weight subgroups. Results: A total of 11,176 reports of linezolid as the “primary suspected” drug and 263 significant adverse events of linezolid were identified, including some common adverse events such as thrombocytopenia ( n = 1,139, ROR 21.98), anaemia ( n = 704, ROR 7.39), and unexpected signals that were not listed on the drug label such as rhabdomyolysis ( n = 90, ROR 4.33), and electrocardiogram QT prolonged ( n = 73, ROR 4.07). Linezolid-induced adverse reactions involved 27 System Organ Class (SOC). Gender differences existed in ADE signals related to linezolid. The median onset time of all ADEs was 6 days, and most ADEs ( n = 3,778) occurred within the first month of linezolid use but some may continue to occur even after a year of treatment ( n = 46). Conclusion: This study reports the time to onset of adverse effects in detail at the levels of SOC and specific preferred term (PT). The results of our study provide valuable insights for optimizing the use of linezolid and reducing potential side effects, expected to facilitate the safe use of linezolid in clinical settings.

•Design specification induces large variation in disproportionality analyses results.•Risks from meta-analyses and disproportionality analyses correlate in most cases.•Objective adverse reactions not linked to the underlying pathology better correlate.•Pharmacovigilance databases could be used to hierarchize a risk among a drug class.•Agreement between methods is poor and relative bias important. We aimed at testing if a correlation between adverse drug reactions relative risks estimated from meta-analyses and disproportionality analyses calculated from pharmacovigilance spontaneous reporting systems databases exist, and if methodological choices modify this correlation. We extracted adverse drug reactions (ADR) odds ratios (ORs) from meta-analyses used as reference and calculated corresponding Reporting Odds Ratios (RORs) from the WHO pharmacovigilance database according to five different designs. We also calculated the relative bias and agreement of ROR compared to ORs. We selected five meta-analyses which displayed a panel of 13 ADRs. A significant correlation for 7 out of the 13 ADRs studied in the primary analysis was found. The methods for ROR calculation impacted the results but none systematically improved the correlations. Whereas correlation was found between OR and ROR, agreement was poor and relative bias was important. Despite the large variation in disproportionality analyses results due to design specification, this study provides further evidence that relative risks obtained from meta-analyses and from disproportionality analyses correlate in most cases, in particular for objective ADR not associated with the underlying pathology.

BackgroundPulmonary aspiration remains a major perioperative patient safety issue. Drug-related impaired gastric emptying (IGE) is a recognized yet underappreciated risk factor for aspiration. With the increasing use of medications such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), concerns have grown regarding their potential to delay gastric emptying and thereby elevate aspiration risk. However, real-world data on drug-related IGE remain limited.ObjectiveTo identify risk factors for drug-related IGE using real-world pharmacovigilance data from the FDA Adverse Event Reporting System (FAERS).MethodsA retrospective pharmacovigilance study was conducted using FAERS data from Q1 2004 through Q2 2025. Disproportionality analysis, logistic regression, LASSO regression and time-to-onset analysis were performed to investigate the association between drugs and IGE from different perspectives.ResultsA total of 731 drugs related to IGE. Six of the top 10 most frequently reported drugs associated with IGE were antidiabetic agents, including five GLP-1RAs: semaglutide, dulaglutide, tirzepatide, exenatide, and liraglutide. Multi-factor analysis identified female sex, age <63 years, and exposure to any of nine specific drugs—including GLP-1RAs, insulin lispro, sodium oxybate, olmesartan, and esomeprazole—as independent risk factors for drug-related IGE. The model achieved an ROC-AUC of 0.739, indicating good discriminatory capability. Time-to-onset analysis revealed an early-failure pattern for all nine drugs.ConclusionOur study shows that female sex, younger age, and use of specific medications are associated with an increased risk of drug-related IGE. These findings may provide valuable evidence to support the early recognition of drug-related IGE and for optimizing anaesthetic plans and perioperative personalized fasting strategies.

BackgroundThe relationship between antidiabetic drugs and thromboembolic events remains unclear. The FDA Adverse Event Reporting System (FAERS) data was used to systematically assess safety signals and polypharmacy-related drug–drug interactions of antidiabetic medications.MethodsBy analyzing FAERS reports from 2004 to 2025 that included antidiabetic drugs, the Reporting Odds Ratio (ROR), the Proportional Reporting Ratio (PRR), the Information Component (IC), and the Empirical Bayes Geometric Mean (EBGM) were used to assess disproportionality. Factors such as the main suspected drug, event seriousness, age, sex, US origin, and the recent reporting period were examined in sensitivity analyses. Drug–drug interactions (DDIs) were evaluated using the Ω shrinkage measure and adjusted for false discovery rate.ResultsWe analyzed 81,280,515 FAERS reports from 2004–2025, of which 498,750 (0.61%) involved at least one of 30 antidiabetic drugs, revealing strong arterial thromboembolic signals for rosiglitazone (IC = 4.68), gliclazide (IC = 1.55), linagliptin (IC = 1.56), dapagliflozin (IC = 1.25), and several DPP-4 inhibitors. Only insulin degludec (IC = 0.73, IC025 = 0.61) and insulin aspart (IC = 0.28, IC025 = 0.21) showed nominal venous thromboembolic signals. For GLP-1 agonists, no thromboembolic signals were detected. These observations were confirmed by sensitivity analyses across all subgroups. Moreover, 257 significant drug–drug interactions were identified, particularly between insulin analogues and simvastatin, acetaminophen, or gabapentin.ConclusionDPP-4 inhibitors, SGLT2 inhibitors, and certain insulins showed positive arterial thromboembolic signals. No positive thromboembolic signals were detected for GLP-1 agonists, consistent with their favorable cardiovascular safety profile observed in randomized controlled trials. Numerous significant drug–drug interactions were also detected, particularly for insulin analogues with other drugs. Further research is necessary to understand the clinical importance of these interactions.