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ABSTRACT Aims/Introduction We assessed the modification effect of adherence to diabetes care on the association between HbA1c levels and the risk of coronavirus disease 2019 (COVID‐19) among individuals with diabetes using a population‐based database. Material and Methods We retrospectively identified individuals with diabetes during routine health checkups performed in 2019 in Japan using a population‐based claims database (JMDC, Tokyo, Japan). We assessed the risk of COVID‐19 infection in 2020 in relation to HbA1c levels during routine checkups, stratified by the presence/absence of follow‐up for diabetes care in 2019. Several sensitivity analyses were performed. Results We identified 65,956 individuals with an HbA1c ≥6.5% and fasting glucose ≥126 mg/dL in routine checkups, including 52,637 and 13,319 with and without at least one physician consultation for diabetes care in 2019, respectively. Although high HbA1c levels were associated with an increased risk of COVID‐19 infection in a dose‐dependent manner among individuals without diabetes care in 2019 (odds ratios, 1.53 and 2.17 in individuals with HbA1c of 7.0–7.9% and ≥8.0%, respectively) with a reference to HbA1c of 6.5–6.9%, individuals with diabetes care had no such trend in 2019 (odds ratios, 0.99 and 0.97 among individuals with HbA1c of 7.0–7.9% and ≥8.0%, respectively). Sensitivity analyses yielded consistent results when the variable definitions were changed and after multivariable adjustment with multiple imputation. Conclusions This population‐based study suggests that adherence to diabetes care may modify the association between HbA1c levels and the risk of COVID‐19 infection.

Abstract Background The risk of subsequent cardiovascular disease (CVD) is high in cancer survivors. Although metabolic syndrome is an established risk factor for CVD, its association with cancer survivors has not yet been established. This study aimed to clarify whether metabolic syndrome is associated with subsequent CVD risk in patients with cancer using a nationwide epidemiological dataset. Methods We retrospectively analysed 53 510 patients with a history of breast, colorectal, or stomach cancer, which is reportedly a major site for developing cancer in Japan. Study participants were categorized into two groups based on the presence of metabolic syndrome, defined using the Japanese criteria (high waist circumference and ≥2 metabolic parameters including elevated blood pressure, elevated triglycerides, reduced high‐density lipoprotein cholesterol, or elevated fasting plasma glucose). The clinical outcomes were collected between 2005 and 2021. The primary endpoint was defined as the composite CVD outcome, including myocardial infarction, angina pectoris, stroke, and heart failure. Results The median patient age was 54 years, and 37.5% of the patients were men. Metabolic syndrome was observed in 5558 (10.4%) patients. Over a mean follow‐up period of 973 ± 791 days, 3085 composite CVD outcomes were recorded. Multivariable Cox regression analyses showed that metabolic syndrome was associated with a greater risk of developing CVD events (HR = 1.29, 95% CI = 1.15–1.45). Metabolic syndrome was also associated with an increased risk of CVD in patients with a follow‐up period ≥1 year (HR = 1.33, 95% CI = 1.15–1.53). This relationship was also observed when metabolic syndrome was defined according to the International Diabetes Federation criteria (HR = 1.34, 95% CI = 1.21–1.49) and the National Cholesterol Education Program Adult Treatment Panel III criteria (HR = 1.32, 95% CI = 1.19–1.46). Subgroup analyses showed that the relationship between metabolic syndrome and incident CVD was more pronounced in the non‐obese participants than in the obese participants. Conclusions Metabolic syndrome is associated with a greater risk of developing CVD, even among cancer survivors.

Background Observational studies have reported associations between primary aldosteronism (PA) and cardiovascular outcomes, including coronary artery diseases (CAD), congestive heart failure (CHF), and stroke. However, establishing causality remains a challenge due to the lack of randomized controlled trial data on this topic. We thus aimed to investigate the causal relationship between PA and the risk of developing CAD, CHF, and stroke. Methods and Results Cross‐ancestry meta‐analysis of genome‐wide association studies combining East Asian and European ancestry (1560 PA cases and 742 139 controls) was conducted to identify single‐nucleotide variants that are associated with PA. Then, using the identified genetic variants as instrumental variables, we conducted the 2‐sample Mendelian randomization analysis to investigate the causal relationship between PA and incident CAD, CHF, and stroke among both East Asian and European ancestry. Summary association results were extracted from large genome‐wide association studies consortia. Our cross‐ancestry meta‐analysis of East Asian and European populations identified 7 genetic loci significantly associated with the risk of PA, for which the genes nearest to the lead variants were CASZ1, WNT2B, HOTTIP, LSP1, TBX3, RXFP2, and NDP. Among the East Asian population, the pooled odds ratio estimates using these 7 genetic instruments of PA were 1.07 (95% CI, 1.03–1.11) for CAD, 1.10 (95% CI, 1.01–1.20) for CHF, and 1.13 (95% CI, 1.09–1.18) for stroke. The results were consistent among the European population. Conclusions Our 2‐sample Mendelian randomization study revealed that PA had increased risks of CAD, CHF, and stroke. These findings highlight that early and active screening of PA is critical to prevent future cardiovascular events.

Background: Despite the widespread practice of Japanese traditional Kampo medicine, the characteristics of patients receiving various Kampo formulations have not been documented in detail. We applied a machine learning model to a health insurance claims database to identify the factors associated with the use of Kampo formulations. Methods: A 10% sample of enrollees of the JMDC Claims Database in 2018 and 2019 was used to create the training and testing sets, respectively. Logistic regression analyses with lasso regularization were performed in the training set to construct models with prescriptions of 10 commonly used Kampo formulations in 1 year as the dependent variable and data of the preceding year as independent variables. Models were applied to the testing set to calculate the C-statistics. Additionally, the performance of simplified scores using 10 or 5 variables were evaluated. Results: There were 338,924 and 399,174 enrollees in the training and testing sets, respectively. The commonly prescribed Kampo formulations included kakkonto, bakumondoto, and shoseityuto. Based on the lasso models, the C-statistics ranged from 0.643 (maoto) to 0.888 (tokishakuyakusan). The models identified both the common determinants of different Kampo formulations and the specific characteristics associated with particular Kampo formulations. The simplified scores were slightly inferior to full models. Conclusion: Lasso regression models showed good performance for explaining various Kampo prescriptions from claims data. The models identified the characteristics associated with Kampo formulation use.

Background There are few data on sex differences in the association between schizophrenia and the development of cardiovascular disease (CVD). We sought to clarify the relationship of schizophrenia with the risk of developing CVDs and to explore the potential modification effect of sex differences. Methods and Results We conducted a retrospective analysis using the JMDC Claims Database between 2005 and 2022. The study population included 4 124 508 individuals aged 18 to 75 years without a history of CVD or renal replacement therapy. The primary end point is defined as a composite end point that includes myocardial infarction, angina pectoris, stroke, heart failure, atrial fibrillation, and pulmonary thromboembolism. During a mean follow‐up of 1288±1001 days, we observed 182 158 composite end points. We found a significant relationship of schizophrenia with a greater risk of developing composite CVD events in both men and women, with a stronger association observed in women. The hazard ratio for the composite end point was 1.63 (95% CI, 1.52–1.74) in women and 1.42 (95% CI, 1.33–1.52) in men after multivariable adjustment (P for interaction=0.0049). This sex‐specific difference in the association between schizophrenia and incident CVD was consistent for angina pectoris, heart failure, and atrial fibrillation. Conclusions Our analysis using a large‐scale epidemiologic cohort demonstrated that the association between schizophrenia and subsequent CVD events was more pronounced in women than in men, suggesting the clinical importance of addressing schizophrenia and tailoring the CVD prevention strategy based on sex‐specific factors.

The 3 Screen ICA ELISA is a novel assay capable of simultaneously measuring autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A), making it a valuable tool for screening type 1 diabetes. Despite its advantages, it cannot specify which individual autoantibodies are positive or negative. This study aimed to estimate individual positive autoantibodies based on the 3 Screen ICA titer. Six hundred seventeen patients with type 1 diabetes, simultaneously measured for 3 Screen ICA and three individual autoantibodies, were divided into five groups based on their 3 Screen ICA titer. The sensitivities and contribution rates of the individual autoantibodies were then examined. The study had a cross-sectional design. Sixty-nine percent (424 of 617) of patients with type 1 diabetes had 3 Screen ICA titers exceeding the 99th percentile cut-off level (20 index). The prevalence of GADA ranged from 80% to 100% in patients with a 3 Screen ICA over 30 index and 97% of patients with a 3 Screen ICA ≥300 index. Furthermore, the prevalence of all individual autoantibodies being positive was 0% for ≤80 index and as high as 92% for ≥300 index. Significant associations were observed in specific titer groups: the 20–29.9 index group when all the individual autoantibodies were negative, the 30–79.9 index group when positive for GADA alone or IA-2A alone, the 30–299.9 index group when positive for ZnT8A alone, the 80–299.9 index group when positive for both IA-2A and ZnT8A, the 300–499.9 index group when positive for both GADA and ZnT8A, and the ≥300 index group when positive for all individual autoantibodies. These results suggest that the 3 Screen ICA titer may be helpful in estimating individual positive autoantibodies.

NTT's laboratories are engaged in a wide range of research and development from basic research to applications, and divided into four laboratory groups. As one of those laboratory groups, NTT Science and Core Technology Laboratory Group carries out research and development with three missions in mind: "Conduct research and development on cutting-edge technologies to expand NTT's business domains," "Create new principles and concepts that will revolutionize society," and "Research and develop technologies that are friendly to the global environment and people." We asked Akira Okada, senior vice president of R&D, head of NTT Science and Core Technology Laboratory Group, about the technology strategy of the laboratory group and his mindset as a top manager. [ABSTRACT FROM AUTHOR]

Background: The Late-Stage Elderly Questionnaire has been incorporated into health assessments for older adults in Japan, encompassing three self-administered questions on subjective physical function: subjective gait speed decline, recent fall history, and exercise habits. Nevertheless, its efficacy in predicting new fracture occurrences remains uncertain. Methods: This retrospective cohort study utilized Japan's DeSC database, a large commercially available claims database. Participants were older adults aged =75 years and provided complete responses to the Late-Stage Elderly Questionnaire at health check-ups. We performed two Cox regression analyses for new fractures based on the responses to the three questions (Model 1) and on age, sex, and responses to the three questions (Model 2). The predictive abilities of the 1-year occurrence of new fractures were compared between the two models. Results: Of 11 683 eligible older adults, 927 (7.93%) experienced new fractures. Model 1 revealed significant associations between new fractures and subjective gait speed decline (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.40-1.89), recent fall history (HR, 2.03; 95% CI, 1.77-2.33), and absence of exercise habits (HR, 1.29; 95% CI, 1.13-1.47). Model 2 demonstrated superior predictive ability (area under the curve, 0.677; 95% CI, 0.659-0.695) compared with Model 1 (area under the curve, 0.633; 95% CI, 0.614-0.652), with a net reclassification improvement of 0.383 (95% CI, 0.317-0.449). Conclusion: Three subjective physical well-being factors were significantly associated with new fracture development in older adults. These results suggest that the three-question assessment may be a valuable screening tool for identifying new fractures. [ABSTRACT FROM AUTHOR]