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Encephalopathy is the most severe complication of various common infections, including influenza and herpes, and it often results in death or severe neurological disability. The risk factors for viral encephalopathy include non-steroidal anti-inflammatory drug (NSAID) use; however, studies on NSAID-related encephalopathy are limited. In this study, we aimed to investigate the characteristics of NSAID-related encephalopathy. We investigated the incidence of NSAID-related encephalopathy using data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases containing reports on spontaneous adverse effects (AEs) published by the Pharmaceuticals and Medical Devices Agency. We used these databases to detect AEs based on reported odds ratios. By separating suspicious drugs, concomitant drugs, and drug interactions involving NSAIDs, we investigated the relationship between encephalopathy pathology and AEs of NSAIDs. Significant encephalopathy signals were detected for loxoprofen and etodolac in the FAERS database and loxoprofen in the JADER database. In the JADER database, significant encephalopathy signals in loxoprofen-treated patients were detected in 70-79-year-old, ≥80-year-old, influenza viral infection, and herpes virus infection groups. Significant encephalopathy signals in patients with herpes virus infection were detected in the ≥80-year-old and loxoprofen-treated groups. Regarding the involvement of loxoprofen in the development of encephalopathy, the JADER database listed loxoprofen as a suspect drug, without indicating any concomitant drug interactions. In conclusion, our findings suggest that loxoprofen and etodolac may be associated with viral encephalopathy. Accordingly, prudence is recommended when using loxoprofen in older individuals with viral infections.

Background: We aimed to assess whether the United States-developed Claims-based Frailty Index (CFI) can be implemented in Japanese older adults using claims data., Methods: We used the monthly claims data and certification of long-term care (LTC) insurance data of residents from 12 municipalities from April 2014 to March 2019. The 12 months from first recording was defined as the "baseline period," and the time thereafter as the "follow-up period". Participants aged ≥65 years were included, and those with no certified LTC insurance or who died at baseline were excluded. New certification of LTC insurance and all-cause mortality during the follow-up period were defined as outcome events. CFI categorization consisted of three steps including: 1) using 12 months deficit-accumulation approach that assigned different weights to each of the 52 items; 2) the accumulated score to derive the CFI; and 3) categorizing the CFI as "robust" (<0.15), "prefrail" (0.15-0.24), and "frail" (≥0.25). Kaplan-Meier survival curves and Cox proportional hazard models were used to determine the association between CFI and outcomes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated., Results: There were 519,941 participants in total. After adjusting for covariates, the severe CFI category had a high risk of certification of LTC insurance (prefrail: HR 1.33; 95% CI, 1.27-1.39 and frail: HR 1.60; 95% CI, 1.53-1.68) and all-cause mortality (prefrail: HR 1.44; 95% CI, 1.29-1.60 and frail: HR 1.84; 95% CI, 1.66-2.05)., Conclusion: This study suggests that CFI can be implemented in Japanese claims data to predict the certification of LTC insurance and mortality.

The protective effect of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) against cardiovascular disease has been investigated in the United States and Europe; however, its effect has not been fully established. This study aimed to investigate the protective effect of PPSV23 on cardiovascular events in adults aged ≥ 65 years. This population-based nested case-control study was conducted using the claims data and vaccine records between April 2015 and March 2020 from the Vaccine Effectiveness, Networking, and Universal Safety (VENUS) Study. PPSV23 vaccination was identified using vaccination records in each municipality. The primary outcome was acute myocardial infarction (AMI) or stroke. The adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for PPSV23 vaccination were calculated using conditional logistic regression. Among 383,781 individuals aged ≥ 65 years, 5,356 and 25,730 individuals with AMI or stroke were matched with 26,753 and 128,397 event-free controls, respectively. Individuals who were PPSV23 vaccinated, compared with the unvaccinated individuals, had significantly lower odds of AMI or stroke events (aOR, 0.70 [95% CI, 0.62-0.80] and aOR, 0.81 [95% CI, 0.77-0.86], respectively). More recent PPSV23 vaccination was associated with lower odds ratios (AMI, aOR 0.55 [95% CI, 0.42-0.72] for 1-180 days and aOR 1.11 [95% CI, 0.84-1.47] for 720 days or longer; stroke, aOR 0.83 [95% CI, 0.74-0.93] for 1-180 days and aOR 0.90 [95% CI, 0.78-1.03] for 720 days or longer). Among Japanese older adults, individuals who were PPSV23 vaccinated, compared with unvaccinated individuals, had significantly lower odds of AMI or stroke events., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Haruhisa Fukuda reports financial support was provided by Japan Agency for Medical Research and Development. Haruhisa Fukuda reports financial support was provided by Japan Society for the Promotion of Science. Haruhisa Fukuda reports financial support was provided by Japan Science and Technology Agency]., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Delays in reporting of medical errors may signal deficiencies in the performance of hospital-based incident reporting. We sought to understand the characteristics of hospitals, providers and patient injuries that affect such delays., Setting and Methods: All incident reports filed between May 2004 and August 2005 at the Kyoto University Hospital (KUH) in Japan and the Brigham and Women's Hospital (BWH) in the USA were evaluated. Lag time between each event and the submission of an incident report were computed. Multivariable Poisson regression with overdispersion, to control for previously described confounding factors and identify independent predictors of delays, was used., Results: Unadjusted lag times were significantly longer for physicians than other reporters (3.6 vs 1.8 days, p < 0.0001), longer for major than minor events (4.1 vs 1.9 days, p = 0.0006) and longer at KUH than at BWH (3.1 vs 1.0 days, p < 0.0001). In multivariable analysis, lag times at KUH remained nearly three times longer than at BWH (incidence-rate ratio 2.95, 95% CI 2.84 to 3.06, p < 0.0001)., Conclusions: Lag time provides a novel and useful metric for evaluating the performance of hospital-based incident reporting systems. Across two very different health systems, physicians reported far fewer events, with significant delays compared with other providers. Even after controlling for important confounding factors, lag times at KUH were nearly triple those at BWH, suggesting significant differences in the performance of their reporting systems, potentially attributable to either the ease of online reporting at BWH or to the greater attention to patient safety reporting in that hospital.

Investigator-initiated clinical trials are essential for improving the standard of care for cancer patients, because pharmaceutical companies do not conduct trials that evaluate combination chemotherapy using drugs from different companies, surgery, radiotherapy or multimodal treatments. Government-sponsored cooperative groups have played a vital role in developing cancer therapeutics since the 1950s in the USA; however, the establishment of these groups in Japan did not take place until 30 years later. Methodological standards for multicenter cancer clinical trials were established in the 1980s by the National Cancer Institute and cooperative groups. The Japan Clinical Oncology Group, one of the largest cooperative groups in the country, was instituted in 1990. Its data center and operations office, formed during the 1990s, applied the standard methods of US cooperative groups. At present, the Japan Clinical Oncology Group consists of 14 subgroups, a Data Center, an Operations Office, nine standing committees and an Executive Committee represented by the Japan Clinical Oncology Group Chair. Quality control and quality assurance at the Japan Clinical Oncology Group, including regular central monitoring, statistical methods, interim analyses, adverse event reporting and site visit audit, have complied with international standards. Other cooperative groups have also been established in Japan since the 1980s; however, nobody figures out all of them. A project involving the restructuring of US cooperative groups has been ongoing since 2005. Learning from the success of this project will permit further progress of the cancer clinical trials enterprise in Japan.

Since the mid-1990s, lethal infections of koi herpesvirus (KHV) have been spreading, threatening the worldwide production of common carp and koi (both Cyprinus carpio). The complete genome sequences of three KHV strains from Japan, the United States, and Israel revealed a 295-kbp genome containing a 22-kbp terminal direct repeat. The finding that 15 KHV genes have clear homologs in the distantly related channel catfish virus (ictalurid herpesvirus 1) confirms the proposed place of KHV in the family Herpesviridae, specifically in the branch with fish and amphibian hosts. KHV thus has the largest genome reported to date for this family. The three strains were interpreted as having arisen from a wild-type parent encoding 156 unique protein-coding genes, 8 of which are duplicated in the terminal repeat. In each strain, four to seven genes from among a set of nine are fragmented by frameshifts likely to render the encoded proteins nonfunctional. Six of the affected genes encode predicted membrane glycoproteins. Frameshifts or other mutations close to the 3' ends of coding sequences were identified in a further six genes. The conclusion that at least some of these mutations occurred in vivo prompts the hypothesis that loss of gene functions might be associated with emergence of the disease and provides a basis for further investigations into the molecular epidemiology of the virus.

Efforts for international harmonization have made it clear that Japan is far behind in Western countries in all aspects of infrastructure for clinical trials. The introduction of ICH-GCP, 1998, has promoted the rapid growth of infrastructure for investigational new drug (IND) trials; however, the infrastructure for academic cancer trials has shown no remarkable progress. There is still no governmental regulation, no agency for quality control, and no quality assurance audit system even in government-sponsored trials. The author introduces the quality control systems in cooperative groups in Western countries, such as the Southwest Oncology Group (SWOG), National Surgical Adjuvant Breast and Bowel Project (NSABP) and European Organization for Research and Treatment of Cancer (EORTC), and the quality assurance systems by the National Cancer Institute-Cancer Therapy Evaluation Program (NCI-CTEP). Key activities for quality control in cooperative groups are in-house monitoring, site visit audits, institutional performance evaluations and case report form review by study coordinators. NCI-CTEP oversees cooperative group activities through protocol review, supervision of site visit audits and a monitoring committee. Cancer cooperative groups in Western countries have taken the initiatives in advancement of trial methodology and establishment of clinical trial infrastructure. In order to improve the quality of clinical trials, there is need to invest cancer cooperative groups, thus strengthening the activities for overall clinical trials.