波多野 正和

Background/Objectives: The risk of fractures associated with immune checkpoint inhibitors (ICIs) is increasing; however, the relationship between fracture risk and potential factors, such as osteoporosis and hyperthyroidism, remains unclear. Methods: Using VigiBase, the World Health Organization's global pharmacovigilance database, we investigated the signals for osteoporosis, hyperthyroidism, and fractures associated with ICIs (nivolumab, pembrolizumab, atezolizumab, durvalumab, ipilimumab, and tremelimumab) by calculating information components (ICs) and their 95% confidence intervals (CIs). Furthermore, we estimated the association between the occurrence of fractures in patients receiving ICIs and osteoporosis or hyperthyroidism. Results: Signals of hyperthyroidism (IC = 4.66, 95% CI: 4.58–4.73), but not osteoporosis (IC = −1.79, 95% CI: −2.22 to −1.36) or fractures (IC = −0.21, 95% CI: −0.36 to −0.06), were detected in patients using ICIs. Osteoporosis (odds ratio: 118.00, 95% CI: 61.00–230.00) was associated with an increased reporting frequency of fractures related to ICIs, whereas hyperthyroidism (odds ratio: 0.60, 95% CI: 0.19–1.87) was not associated with such an increase. Conclusions: The VigiBase analysis indicates that the use of ICIs does not increase the reporting frequency of osteoporosis or fractures. Additionally, hyperthyroidism did not increase the reporting frequency of fractures associated with ICIs.

The United States Food and Drug Administration approved the xanomeline-trospium combination in September 2024 for treating schizophrenia, based in part on three double-blind, randomized placebo-controlled trials in adults with schizophrenia experiencing acute psychosis. This random-effects model pairwise meta-analysis of those three trials found that xanomeline-trospium was comparable to placebo in terms of all-cause discontinuation, discontinuation rate due to adverse events, Simpson-Angus Scale score change, Barnes Akathisia Rating Scale score change, body weight change, body mass index change, blood pressure change, serum total cholesterol change, blood glucose change, QTc interval changes, and the incidence of headache, somnolence, insomnia, dizziness, akathisia, agitation, tachycardia, gastroesophageal reflux disease, diarrhea, increased weight, and decreased appetite. However, xanomeline-trospium was associated with a higher incidence of at least one adverse event, dry mouth, hypertension, nausea, vomiting, dyspepsia, and constipation, and increased serum triglyceride compared with placebo. Notably, xanomeline-trospium demonstrated superior efficacy than placebo in improving the Positive and Negative Syndrome Scale (PANSS) total score, PANSS positive subscale score, and PANSS negative subscale score.

Dummy.

BACKGROUND/AIM: The use of hypnotic drugs can lead to accidents and injuries. However, few reports have shown their association with these events after adjusting for many concomitant medications. This study aimed to determine whether the use of hypnotic drugs was associated with accidents and injuries. PATIENTS AND METHODS: Using the Japanese Adverse Event Reporting Database, 772,387 reports published between September 2023 and April 2004 were analyzed. Reporting odds ratios (RORs) and 95% confidence intervals (CIs) for accidents and injuries associated with each hypnotic drug were calculated after adjusting for potential confounders. RESULTS: Of the total, 12,484 reports indicated association of hypnotic drugs with accidents and injuries. The use of each hypnotic drug was associated with accidents, injuries, and other adverse events. However, a multivariate analysis adjusted for age, sex, reporting year, and concomitant medications showed a considerable decrease in ROR for melatonin receptor agonists (adjusted ROR=1.26; 95%CI=1.03-1.55) and dual orexin receptor antagonists (DORAs) (adjusted ROR=1.04; 95%CI=0.86-1.25). Particularly in DORAs, a loss of signal for accidents and injuries was observed. CONCLUSION: The risk of accidents and injuries may vary with hypnotic drug use; however, DORAs may be less frequently associated with these events. The results of this study provide useful information for the selection of hypnotic drugs.