Background: The use of a statistical approach to analyze cumulative adverse event (AE) reports has been encouraged by regulatory authorities. However, data variations affect statistical analyses (eg, signal detection). Further, differences in regulations, social issues, and health care systems can cause variations in AE data. The present study examined similarities and differences between two publicly available databases, ie, the Japanese Adverse Drug Event Report (JADER) database and the US Food and Drug Administration Adverse Event Reporting System (FAERS), and how they affect signal detection. Methods: Two AE data sources from 2010 were examined, ie, JADER cases (JP) and Japanese cases extracted from the FAERS (FAERS-JP). Three methods for signals of disproportionate reporting, ie, the reporting odds ratio, Bayesian confidence propagation neural network, and Gamma Poisson Shrinker (GPS), were used on drug-event combinations for three substances frequently recorded in both systems. Results: The two databases showed similar elements of AE reports, but no option was provided for a shareable case identifier. The average number of AEs per case was 1.6±1.3 (maximum 37) in the JP and 3.3±3.5 (maximum 62) in the FAERS-JP. Between 5% and 57% of all AEs were signaled by three quantitative methods for etanercept, infliximab, and paroxetine. Signals identified by GPS for the JP and FAERS-JP, as referenced by Japanese labeling, showed higher positive sensitivity than was expected.
Conclusion: The FAERS-JP was different from the JADER. Signals derived from both datasets identified different results, but shared certain signals. Discrepancies in type of AEs, drugs reported, and average number of AEs per case were potential contributing factors. This study will help those concerned with pharmacovigilance better understand the use and pitfalls of using spontaneous AE data.

Background: Suicide amidst the coronavirus disease (COVID-19) pandemic is an important issue. In Japan, the number of suicides in April 2020 decreased by nearly 20% from that in 2019. To assess the impact of an infectious disease pandemic, excess mortality is often discussed. Our main purpose was evaluating excess mortality from suicide in Japan during the early pandemic period.Methods: We used data on suicides collected by the National Police Agency of Japan until June 2020. We estimated excess mortality during the early pandemic period (March–June 2020) using a time-series model of the number of suicides before the pandemic. A quasi-Poisson model was employed for the estimation. We evaluated excess mortalities by the categories of age and sex, and prefectures.Results: No significant excess mortality was observed throughout the early pandemic; instead, a downward trend in the number of suicides for both sexes was noted. For males, negative values of excess mortalities below the lower bound of the 95% prediction interval were observed in April and May. All numbers of females during the period were included in the interval, and the excess mortalities in June were positive and higher than those in April and May. In Tokyo, the number of suicides was below the lower bound throughout the period.Conclusion: Our results suggest that various changes such as communication, and social conditions amid the early COVID-19 pandemic induced a decrease in suicides in Japan. However, continuous monitoring is needed to evaluate the long-term effects of the pandemic on suicides.

Purpose: This study evaluated the efficacy of tiotropium/olodaterol vs tiotropium on lung function, exercise capacity, and physical activity in patients with COPD. Patients and methods: A total of 184 patients aged ≥40 years with COPD (Global Initiative for Chronic Obstructive Lung Disease stage II–IV) received tiotropium/olodaterol for 6 weeks, then tiotropium for 6 weeks, or vice versa. The primary endpoint was inspiratory capacity (IC) at peak post-dose. Results: Adjusted mean IC after 6-week treatment was 1.990 L with tiotropium/olodaterol vs 1.875 L with tiotropium (difference: 115 mL; 95% CI: 77, 153; p<0.0001). Forced expiratory volume in 1 s (difference: 105 mL; 95% CI: 88, 123), forced vital capacity (difference: 163 mL; 95% CI: 130, 197), and slow vital capacity (difference: 134 mL; 95% CI: 91, 176) improved with tiotropium/olodaterol (all p<0.0001). Adjusted mean 6-min walk distance was similar between treatments in the overall population but was significantly increased with tiotropium/olodaterol in the subgroup with Global Initiative for Chronic Obstructive Lung Disease stage III/IV at baseline (difference: 18.1 m; 95% CI: 2.3, 33.9; p=0.0254). In a post hoc analysis, tiotropium/olodaterol improved the values for ≥2.0 metabolic equivalents (difference: 5.0 min; 95% CI: 0.4, 9.7; p=0.0337). Conclusion: Tiotropium/olodaterol significantly improved IC compared with tiotropium and potentially enhanced the exercise capacity in COPD patients. A slight improvement in physical activity of relatively more than moderate intensity was also seen with tiotropium/olodaterol.

Although the economic burden of multimorbidity is a growing global challenge, the contribution of multimorbidity in patients with high medical expenses remains unclear. We aimed to clarify multimorbidity patterns that have a large impact on medical costs in the Japanese population. We conducted a cross-sectional study using health insurance claims data provided by the Japan Health Insurance Association. Latent class analysis (LCA) was used to identify multimorbidity patterns in 1,698,902 patients who had the top 10% of total medical costs in 2015. The present parameters of the LCA model included 68 disease labels that were frequent among this population. Moreover, subgroup analysis was performed using a generalized linear model (GLM) to assess the factors influencing annual medical cost and 5-year mortality. As a result of obtaining 30 latent classes, the kidney disease class required the most expensive cost per capita, while the highest portion (28.6%) of the total medical cost was spent on metabolic syndrome (MetS) classes, which were characterized by hypertension, dyslipidemia, and type 2 diabetes. GLM applied to patients with MetS classes showed that cardiovascular diseases or complex conditions, including malignancies, were powerful determinants of medical cost and mortality. MetS was classified into 7 classes based on real-world data and accounts for a large portion of the total medical costs. MetS classes with cardiovascular diseases or complex conditions, including malignancies, have a significant impact on medical costs and mortality.

Background: Japan has witnessed an unusual increase in the number of suicides among women during the coronavirus disease 2019 pandemic. An analysis is required to identify the influencing factors during the pandemic and develop new measures for preventing suicides.Methods: Data on the number of monthly suicides were collected from the National Police Agency of Japan. The expected number of suicides among women during the pandemic was estimated using a time-series model based on pre-pandemic data, considering year-to-year trends. The observation-to-expectation (O/E) ratio of suicides was estimated from March 2020 to October 2021 using job status, suicide motive, and age.Results: The number of suicides among women in Japan increased beyond the expected number until October 2021. The O/E ratio based on job status, suicide motive, and age (except self-employed, unknown job status, and women ≥80 years) was significantly above 1.0 from March–December 2020, and the increase in suicides continued in almost all categories in 2021.Conclusion: Although several reasons were reported for increased suicides among women in Japan during the pandemic (e.g., economic downturn, financial instability, and loneliness), suicides increased irrespective of job status, suicide motive, or age. The preventive measures for suicide without omission might have been important during the pandemic, as opposed to limiting interventions to the reported specific aspects.