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Clinical evidence of oral inotrope use for advanced heart failure (HF) is limited. This study investigated the contemporary use and association of oral inotropes with prognosis in the outpatient treatment of advanced HF using a nationwide administrative claims database in Japan. Patients hospitalized with acute HF between 2014 and 2021 were identified from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Associations of the drug use after discharge with the 2-year prognosis were examined in a propensity-matching cohort, and hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Of the 428,650 patients discharged with HF in 4433 hospitals, 14,374 (3.4%) had taken oral inotropes, most of whom (95.0%) took pimobendan. Patients taking oral inotropes were younger and more likely to receive HF drugs. Cardiomyopathy as the etiology and the use of intravenous inotropes during hospitalization were more frequently observed. In the 2-year prognosis, oral inotrope use was associated with higher all-cause mortality and HF rehospitalization rates (HR [95% CI]: 1.59 [1.51, 1.66] and 1.54 [1.48, 1.61], respectively). Concomitant use of pimobendan and β-blockers was associated with lower mortality and HF rehospitalization (0.81 [0.74, 0.88] and 0.85 [0.79, 0.92], respectively) compared with pimobendan without β-blockers. Although no association was found between oral inotrope use and favorable prognosis, concomitant use of β-blockers may be a better strategy for oral inotrope use in advanced HF., (© 2025, The American College of Clinical Pharmacology.)

Aim/introduction: Although immune checkpoint inhibitor-related type 1 diabetes mellitus (ICI-T1DM) is a rare condition, it is of significant concern globally. We aimed to elucidate the precise incidence, risk factors, and impact of ICI-T1DM on survival outcomes., Materials and Methods: The study is a large retrospective cohort study, performed using the DeSC Japanese administrative claims database comprising 11 million patients. The database population is reportedly similar to the entire population of Japan. Patients administered ICI between 2014 and 2022 were enrolled in the study, including 21,121 patients. The risk factors for ICI-T1DM development and their characteristics were evaluated by logistic regression analysis. Development of a new irAE after the day following the first administration of ICI was set as the study outcome., Results: ICI-T1DM was observed in 102 (0.48%) of the 21,121 patients after ICI initiation. PD-(L)1 and CTLA-4 combination therapy was associated with an increased risk of ICI-T1DM compared with PD-1 monotherapy (odds ratio [OR], 2.36; 95% confidence interval [CI], 1.21-4.58; P = 0.01). Patients with a prior diagnosis of diabetes mellitus (OR, 1.59; 95% CI, 1.03-2.46; P = 0.04) or hypothyroidism (OR, 2.48; 95% CI, 1.39-4.43; P < 0.01) also exhibited an increased risk of ICI-T1DM. The Kaplan-Meier analysis revealed that patients with ICI-T1DM showed higher survival rates than those without (log-lank test, P < 0.01). Multivariable Cox regression analysis demonstrated that ICI-T1DM development was associated with lower mortality (hazard ratio, 0.60; 95% CI, 0.37-0.99; P = 0.04)., Conclusions: Collectively, the results of this study demonstrate the precise incidence and risk factors of ICI-T1DM. The development of ICI-T1DM, like other irAEs, is associated with higher survival rates., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

No updated data on people living with HIV (PLHIV) in Japan have been available since 2015, leaving a critical gap in understanding the current status of care and treatment. Therefore, this study aimed to conduct a nationwide evaluation of the second and third goals of the "90-90-90 target" defined by UNAIDS between 2016 and 2020. The study utilized data from approximately 360 core hospitals through structured questionnaires and the National Database of Health Insurance Claims and Specific Health Checkups (NDB). Key findings revealed that over 95% of diagnosed outpatients were retained in care (second 90), and more than 99% achieved successful viral suppression (third 90). A significant transition to single-tablet regimens and newer, highly effective antiretroviral drugs was observed, optimizing treatment adherence and outcomes. These results underscore the efficacy of Japan's universal health insurance system in ensuring consistent access to HIV care and treatment, supporting both individual patient outcomes and national surveillance efforts., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Yokomaku et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The 5-aminosalicylic acid (5-ASA) agents are first-line drugs for ulcerative colitis (UC). However, intolerance as well as other issues have been reported for these drugs, making it difficult to sustain this treatment; accordingly, the persistence of 5-ASA is an important indicator of UC treatment strategy. We aimed to analyze the persistence of 5-ASA in patients with UC in Japan. This was a 1-year, nationwide, population-based cohort study using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. We identified patients who were assigned UC-related disease codes and newly prescribed 5-ASA between April 2015 and September 2019 and specified the number of days until 5-ASA prescriptions were interrupted during a follow-up of up to 365 days. Among the 137 million patients who were covered by the universal health insurance in Japan during the study period, 68,234 eligible patients were identified. The 5-ASA persistence in these patients were 87.2%, 65.6%, and 56.4% after 30, 180, and 365 days, respectively. The 5-ASA persistence by subtype at 365 days was 54.4%, 56.4%, and 57.6% for time-dependent, pH-dependent, and multi-matrix system types, respectively. The 5-ASA persistence rate after 365 days was 65.0% for those under 20 years of age, 51.0% for those 20-39 years old, 57.5% for those 40-64 years old, and 65.5% for those over 64 years of age. This study revealed the 1-year persistence of newly prescribed 5-ASA in patients with UC newly prescribed 5-ASA in Japan, based on a national claims database of more than 100 million individuals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Noda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Evidence of the effectiveness of β-blockers in heart failure (HF) and atrial fibrillation (AF) in a contemporary cohort is controversial. This study investigated the association between the use of β-blockers and prognosis in hospitalized HF patients with and without AF in Japan. Patients hospitalized with the first episode of acute HF were identified from the National Database of Health Insurance Claims and Specific Health Checkups of Japan between April 2014 and March 2021. Associations of β-blocker use and prognosis were compared by propensity score matching among the AF or non-AF group. A mixed-effects survival model was used, and hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Among 428,650 patients discharged with HF in 4,433 hospitals, 175,174 (40.9%) were ≥ 85 years old, 151,873 (35.4%) had complicated AF, and 236,457 (55.2%) were β-blocker users. In a matched AF group, β-blocker use was associated with a lower composite outcome of all-cause mortality or HF rehospitalization (HR [95% CI], 0.95 [0.93-0.97]). A similar result was obtained in a matched non-AF group (0.95 [0.94-0.96]). In addition, the HRs in patients aged ≥ 85 years and female patients were 1.00 [0.98-1.02] and 1.01 [0.98-1.03] in the AF group and 1.03 [1.01-1.05] and 0.98 [0.97-1.00] in the non-AF group, respectively. The favorable prognostic associations of β-blocker use were observed regardless of AF in patients across a broad spectrum of HF in a superaged society., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

Estimated glomerular filtration rate (eGFR) variation is associated with end-stage kidney disease (ESKD) development in patients with chronic kidney disease; whether annual variations in eGFR at health check-ups is associated with ESKD risk in the general population is unclear. We conducted a retrospective cohort study using Japanese national medical insurance claims from 2013 to 2020. Individuals who had their eGFR levels measured three times in annual health check-ups were included (N = 115,191), and the coefficient of variation of eGFR (CVeGFR) was calculated from 3-point eGFR. The end-point was ESKD as reported in the claims data. We analyzed the association between CVeGFR and ESKD incidence after adjusting for conventional ESKD risk factors. The CVeGFR median distribution was 5.7% (interquartile range: 3.5-8.5%). During a median follow-up period of 3.74 years, 164 patients progressed to ESKD. ESKD incidence was significantly higher in the highest quartile group (CVeGFR ≥ 8.5%) than in the other groups (P < 0.0001). After adjusting for risk factors, individuals with CVeGFR ≥ 8.5% had a significantly high ESKD incidence (adjusted hazard ratio: 3.01; 95% CI 2.14-4.30). High CVeGFR in annual health check-ups was associated with high ESKD incidence, independent of its other conventional risk factors, in the general population., (© 2024. The Author(s).)

Introduction: A well-established association exists between health and neighborhood land use patterns, including parks, roads, and other physical environments, also called the built environment. Previous studies have demonstrated that the built environment influences health, particularly among older populations, because the scope of activities in such populations is limited. Herein, we investigated the association between specific neighborhood environments and the healthy life expectancy of older individuals., Methods: Data at two time points (2013 and 2019) from the Japan Gerontological Evaluation Study were used in this study. The study comprised a sample of 8,956 residents aged ≥65 years who were not certified for long-term care. Information on the presence or absence of eight types of neighborhood environments was collected using a questionnaire. A multistate life table analysis was conducted to determine the association between perceived neighborhood environments and healthy life expectancy., Results: Significant differences were observed in the "parks and sidewalks suitable for exercise and walking" category. The group that perceived "parks and sidewalks suitable for exercise and walking" had an approximately 1.2-year longer healthy life expectancy than the group that did not perceive such parks and sidewalks. In addition, individuals who lived within walking distance of a park were more physically active than those who did not., Conclusions: Safe, walkable neighborhoods with excellent parks may encourage physical activity among older adults and extend their healthy lifespan. Future research is warranted to identify the underlying mechanisms., Competing Interests: None, (Copyright © Japan Medical Association.)

Background and Aims: Few recent large-scale studies have evaluated the risks and benefits of continuing oral anticoagulant (OAC) therapy after catheter ablation (CA) for atrial fibrillation (AF). This study evaluated the status of continuation of OAC therapy and the association between continuation of OAC therapy and thromboembolic and bleeding events according to the CHADS2 score., Methods: This retrospective study included data from the Japanese nationwide administrative claims database of patients who underwent CA for AF between April 2014 and March 2021. Patients without AF recurrence assessed by administrative data of the treatment modalities were divided into two groups according to continuation of OAC therapy 6 months after the index CA. The primary outcomes were thromboembolism and major bleeding after a landmark period of 6 months. After inverse probability of treatment weighting analysis, the association between OAC continuation and outcomes was determined according to the CHADS2 score., Results: Among 231 374 patients included, 69.7%, 21.6%, and 8.7% had CHADS2 scores of ≤1, 2, and ≥3, respectively. Of these, 71% continued OAC therapy at 6 months. The OAC continuation rate was higher in the high CHADS2 score group than that in the low CHADS2 score group. Among all patients, 2451 patients (0.55 per 100 person-years) had thromboembolism and 2367 (0.53 per 100 person-years) had major bleeding. In the CHADS2 score ≤1 group, the hazard ratio of the continued OAC group was 0.86 [95% confidence interval (CI): 0.74-1.01, P = .06] for thromboembolism and was 1.51 (95% CI: 1.27-1.80, P < .001) for major bleeding. In the CHADS2 score ≥3 group, the hazard ratio of the continued OAC group was 0.61 (95% CI: 0.46-0.82, P = .001) for thromboembolism and was 1.05 (95% CI: 0.71-1.56, P = 0.81) for major bleeding., Conclusions: This observational study suggests that the benefits and risks of continuing OAC therapy after CA for AF differ based on the patient's CHADS2 score. The risk of major bleeding due to OAC continuation seems to outweigh the risk reduction of thromboembolism in patients with lower thromboembolic risk., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: Although mortality and disability are known to be associated with health expectancy (LE), few studies have assessed the extent to which a reduction in their prevalence can extend a person's LE. Moreover, differences in this relationship based on gender have not been established. Thus, in this study, we constructed a regression model using the rate of mortality and prevalence of disability to predict LE in older adults (≥65 years) and assess the relationships between LE, mortality rate, and disability prevalence based on gender., Methods: Data were collected from Japan's population registry and long-term insurance records (N = 344). Multiple linear regression was used to analyze the relationship between LE, mortality rate, and disability prevalence, stratified by gender., Results: Age-adjusted mortality rate and disability prevalence significantly predicted LE and were significantly correlated with the measured LE index for both genders. For every 1% annual decrease in age-adjusted mortality, LE increased by 1.54 years for men and 2.15 years for women. Similarly, a 1% annual decrease in age-adjusted disability prevalence increased LE by 0.22 years for men and 0.32 years for women. The regression model coefficients indicated that the strength of the association between LE, mortality rate, and disability prevalence differed between genders. Our model accurately predicted LE (men: adjusted R 2 = 0.968, women: adjusted R 2 = 0.994)., Conclusions: Health promotion policies that are geared toward increasing health expectancy can be evaluated using mortality rate and disability prevalence as prognostic indicators. The strength of the association between LE, mortality, and disability differed between genders, suggesting the need for gender-specific policy planning to increase LE for both genders., Competing Interests: None, (Copyright © Japan Medical Association.)

Background: Obesity is associated with various complications and decreased life expectancy, and substantial heterogeneity in complications and outcomes has been observed. However, the subgroups of obesity have not yet been clearly defined. This study aimed to identify the subgroups of obesity especially those for target of interventions by cluster analysis., Methods: In this study, an unsupervised, data-driven cluster analysis of 9,494 individuals with obesity (body mass index ≥ 35 kg/m 2 ) was performed using the data of ICD-10, drug, and medical procedure from the healthcare claims database. The prevalence and clinical characteristics of the complications such as diabetes in each cluster were evaluated using the prescription records. Additionally, renal and life prognoses were compared among the clusters., Results: We identified seven clusters characterised by different combinations of complications and several complications were observed exclusively in each cluster. Notably, the poorest prognosis was observed in individuals who rarely visited a hospital after being diagnosed with obesity, followed by those with cardiovascular complications and diabetes., Conclusions: In this study, we identified seven subgroups of individuals with obesity using population-based data-driven cluster analysis. We clearly demonstrated important target subgroups for intervention as well as a metabolically healthy obesity group., (© 2024. The Author(s).)

Background: Biologics are increasingly being used in patients with severe uncontrolled asthma. However, the trends in their use for treating severe asthma in Japan remain unclear., Methods: The number of patients with asthma prescribed omalizumab or mepolizumab between April 2017 and March 2018 was estimated according to sex, age, and geographical region using data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan., Results: Overall, 5,014, 3,449 and 7,977 patients were prescribed omalizumab, mepolizumab, or either combination, respectively. The total number of patients prescribed biologics displayed a bimodal distribution with peaks in their early teens and seventies. Biologics were most commonly used by male and female patients in their seventies. Prescription was 1.24 times higher in males than in females up to the teenage years, whereas it was 1.95 times higher in females than in males from their twenties onwards. Omalizumab was prescribed 1.45 times more frequently than mepolizumab, especially in pediatric patients, and was prescribed 1.96 times more often to female patients than to male patients. Regional differences were observed in the proportion of patients prescribed biologics. Correlation analysis suggested a weak relationship (r = 0.3226, p = 0.0270) between the proportion of patients prescribed biologics and board-certified allergists according to the geographic region., Conclusions: In Japan, biologics are prescribed more often to older patients with severe asthma compared to those in other countries. Thus, eliminating the regional disparities in asthma treatment by specialists is necessary to provide appropriate medical care to patients with severe asthma., Competing Interests: Declaration of competing interest YN received consulting fees and an honorarium for speakers bureaus from Novo Nordisk, Daiichi Sankyo, and Sanofi. TM received consulting fees from the Health Insurance Claims Review & Reimbursement services. HM received a research grant from GlaxoSmithKline Japan that was unrelated to the submitted work. TIno received a research grant from Johnson & Johnson Vision Care, SEED Co., Ltd., Novartis Pharma K·K., and Kowa Company, Ltd that was unrelated to the submitted work, consulting fees from Santen Pharmaceutical Co., Ltd. and InnoJin, Inc., and stock or stock options from InnoJin, Inc. MF received an honorarium for speakers bureaus from Sanofi K·K., Kyorin Pharmaceutical Co., Ltd., and Novartis Pharma Co., Ltd. The other authors have no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Although antithyroid drug (ATD)-induced agranulocytosis is a significant concern, its risks associated with long-term use and re-administration are not fully elucidated. Therefore, we performed this study to determine the incidence of ATD-induced leukopenia and G-CSF administration using administrative claims database. Retrospective cohort study. This study was performed using the DeSC Japanese administrative claims database. A total of 12,491 patients with newly diagnosed Graves' disease (GD) who received methimazole or propylthiouracil between April 2014, and February 2021 among 3.44 million patients in the database were included in the study. We measured the six-year incidence of leukopenia and granulocyte colony-stimulating factor (G-CSF) administration. The incidence of leukopenia and G-CSF administration was 1.34% (168 patients) and 0.30% (38 patients), respectively. Leukopenia had a dose-dependent and biphasic incidence. The incidence of leukopenia and G-CSF administration was 37.2 (0.7%) and 8.0 (0.2%) per 1000 person-years during the first 72 days of ATD initiation, whereas it was 3.1 and 0.7 per 1000 person-years during the subsequent 6 years, respectively. The incidence of both outcomes was comparable between first administration and re-administration of ATD. The incidence of ATD-induced leukopenia and G-CSF administration was high in the first 72 days, with a reduced risk for at least 6 years thereafter. The incidence was similar between first administration and re-administration. ATD, a standard therapy, is often administered for a long period; therefore, our findings can guide the treatment of GD., (© 2023. The Author(s).)

Aims: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) improves clinical outcomes in patients with heart failure (HF), but has limited evidence of SGLT2i use in early-phase acute coronary syndrome (ACS). We determined association of early SGLT2i use compared with either non-SGLT2i or dipeptidyl peptidase 4 inhibitor (DPP4i) use in hospitalized patients with ACS., Methods and Results: This retrospective cohort study that used the Japanese nationwide administrative claims database included patients hospitalized with ACS aged ≥20 years between April 2014 and March 2021. The primary outcome was a composite of all-cause mortality or HF/ACS rehospitalization. Using 1:1 propensity score matching, the association with outcomes of the early SGLT2i use (≤14 days after admission) compared with non-SGLT2i or DPP4i use was determined according to the HF treatment. Among 388 185 patients included 115 612 and 272 573 with and without severe HF, respectively. Compared to non-SGLT2i users, the SGLT2i users had a lower hazard ratio (HR) with the primary outcome [HR: 0.83, 95% confidence interval (CI): 0.76-0.91; P < 0.001] in the severe HF group; however, there was no significant difference in the non-severe HF group (HR: 0.92, 95% CI: 0.82-1.03; P = 0.16). SGLT2i use showed a lower risk of the outcome in patients with severe HF and diabetes compared with DPP4i use (HR: 0.83, 95% CI: 0.69-1.00; P = 0.049)., Conclusion: SGLT2i use in patients with early-phase ACS showed a lower risk of primary outcome in patients with severe HF, but the effect was not apparent in patients without severe HF., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

We investigated the risk factors for mortality of hip fracture in the elderly using the National Database of Health Insurance Claims in Japan, and survival was significantly related to sex, age, fracture type, surgical procedure, delayed operative date, comorbidities, blood transfusions, and pulmonary embolism., Purpose: Hip fracture is the most common fracture in the elderly and is known to have a high mortality rate. In Japan, to the best of our knowledge, no studies have reported on mortality risk factors for hip fracture using nationwide registry databases. This study aimed to determine the number of occurrences of hip fracture and factors that increase mortality using the National Database of Health Insurance Claims and Specific Health Checkups of Japan., Methods: This study included extracted data from patients who were hospitalized and underwent surgical treatment for hip fracture between 2013 and 2021, using a nationwide health insurance claims database in Japan. Patient characteristics, such as sex, age, fracture type, surgical procedure, delayed operative date, comorbidities, blood transfusions, and pulmonary embolism, were tabulated to obtain 1-year and in-hospital mortality rates., Results: Both 1-year and in-patient survival were significantly lower in men, older patients, patients who underwent surgery after 3 days of admission, and patients with trochanteric and subtrochanteric fractures, internal fixation, more preoperative comorbidities, blood transfusions, and pulmonary embolism., Conclusions: Survival was significantly related to sex, age, fracture type, surgical procedure, delayed operative date, comorbidities, blood transfusions, and pulmonary embolism. As the number of male patients with hip fracture will increase with the aging of society, medical staff must provide sufficient information before surgery to avoid postoperative mortality., (© 2023. The Author(s).)

Background: This study aimed to clarify the variations in the quality of care provided to patients with acute coronary syndrome (ACS) and to investigate the association between quality of care and mortality at both hospital and patient levels with the use of a nationwide database., Methods: Patients with ACS who underwent percutaneous coronary intervention (PCI) from April 2014 to March 2018 were included from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Twelve quality indicators (QIs) available from administrative data and the association of the QIs with all-cause mortality were investigated., Results: From the analysis of 216,436 patients from 1215 hospitals, adherence to PCI on admission day, aspirin use on arrival, P2Y12 inhibitor use, and left ventricular function assessment were high (median proportion > 90%), and adherence to outpatient cardiac rehabilitation was low (median proportion < 10%). At the hospital level, acute-phase composite QI score was associated with reduced risk-adjusted 30-day mortality (β = -0.92 [95% confidence interval -1.19 to -0.65]; P < 0.001). At the patient level, all acute-phase and subacute-phase QIs were inversely associated with 30-day and 2-year mortalities, respectively (all P < 0.001)., Conclusions: Substantial variations in ACS care were observed in the current nationwide database. High adherence to the QI sets was associated with significant survival gains at both hospital and patient levels. Multilevel approach in QI assessment may be effective for improvement of survival in this population., (Copyright © 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Patient data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) are used to assess the effect of biguanide administration on rates of lactic acidosis (LA) in hospitalized diabetes mellitus (DM) patients. In this retrospective cohort study (from April 2013 to March 2016), we compare DM inpatients prescribed biguanides to DM inpatients who were not prescribed biguanides to quantify the association between biguanides and incidence of LA. In total, 8,111,848 DM patient records are retrieved from the NDB. Of the 528,768 inpatients prescribed biguanides, 782 develop LA. Of the 1,967,982 inpatients not prescribed biguanides, 1310 develop LA. The rate ratio of inpatients who develop LA and are administered biguanides to those who developed LA without receiving biguanides is 1.44 (95% CI, 1.32-1.58). Incidence rates and rate ratios for both sexes are elevated in the group prescribed biguanides for patients aged 70 years and older, markedly in those 80 years and older: 40.12 and 6.31 (95% CI, 4.75-8.39), respectively, for men and 34.96 and 5.40 (95% CI, 3.91-7.46), respectively, for women. Biguanides should be used conservatively in patients older than 70 years, particularly for those with comorbidities, and with caution in patients 80 years and older.

Background: We aimed to validate a claims-based diagnostic algorithm to identify hospitalized patients with acute major cardiovascular diseases (CVDs) from health insurance claims in Japan., Methods and results: This retrospective multicenter validation study was conducted at 4 institutes, including Japanese Circulation Society-certified and uncertified hospitals in Japan. Data on patients with CVDs in departmental lists or with International Classification of Diseases, 10th Revision (ICD-10) codes for CVDs hospitalized between April 2018 and March 2019 were extracted. We examined the sensitivity and positive predictive value of a diagnostic algorithm using ICD-10 codes, medical examinations, and treatments for acute coronary syndrome (ACS), acute heart failure (HF), and acute aortic disease (AAD). We identified 409 patients with ACS (mean age 70.6 years; 24.7% female), 615 patients with acute HF (mean age 77.3 years; 46.2% female), and 122 patients with AAD (mean age 73.4 years; 36.1% female). The respective sensitivity and positive predictive value for the algorithm were 0.86 (95% confidence interval [CI] 0.82-0.89) and 0.95 (95% CI 0.92-0.97) for ACS; 0.74 (95% CI 0.70-0.77) and 0.79 (95% CI 0.76-0.83) for acute HF; and 0.86 (95% CI 0.79-0.92) and 0.83 (95% CI 0.76-0.89) for AAD., Conclusions: The validity of the diagnostic algorithm for Japanese claims data was acceptable. Our results serve as a foundation for future studies on CVDs using nationwide administrative data.

While many types of genetically modified (GM) food have become more available worldwide, the acceptance of GM food continues to be low. To increase this acceptance, various educational interventions have been conducted; however, conflicts remain about the safety and acceptability of GM food among laypeople, experts, and policymakers in several countries. Thus, this study aimed to clarify whether basic biology education influences Japanese people's acceptance of GM food. We examined this idea by comparing individual experiences of high school biology education based on curriculum and proficiency level. We distributed online questionnaires to 1,594 people in Japan; 1,122 valid responses (70.4%) were obtained. Results showed that the acceptance rates of GM vegetables, fish, and meat were 33.6%, 29.0%, and 29.1%, respectively. Comparing the biology knowledge test scores according to different high school biology education levels (i.e., non-learners, basic, and advanced levels) showed no significant differences between the three age groups (20s, 30s, and 40s), which corresponded to different curricula (p = 0.90); however, there were significant differences between the high school biology education levels (p<0.01). Using logistic regression analysis, we then examined the effect of high school biology education on acceptance of GM food. The results showed no significant differences between different high school biology education levels but significantly lower acceptance by the 30s and 40s groups compared with the 20s group (p<0.05). This suggests that basic biology education alone is not sufficient to change people's attitudes toward GM foods. These generational differences suggest factors other than high school biology curriculum affect different generations' acceptance of GM foods. Overall, high school biology education did not directly affect acceptance of GM foods, although those who received a higher level of education had an increased knowledge of GM foods., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mine et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Healthy life expectancy (HLE) remains the principal target of various health plans. We aimed to identify the areas of priority and determinants of mortality to extend HLE across local governments in Japan., Methods: HLE according to secondary medical areas was calculated using the Sullivan method. People requiring long-term care of level 2 or higher were considered unhealthy. Standardized mortality ratios (SMRs) for major causes of death were calculated using vital statistics data. The association between HLE and SMR was analyzed using simple and multiple regression analyses., Results: The average (standard deviation) HLE values were 79.24 (0.85) and 83.76 (0.62) years for men and women, respectively. A comparison of HLE revealed regional health gaps of 4.46 (76.90-81.36) and 3.46 (81.99-85.45) years for men and women, respectively. The coefficients of determination for the SMR of malignant neoplasms with HLE were the highest and were 0.402 and 0.219 among men and women, respectively, followed by those of cerebrovascular diseases, suicide, and heart diseases among men and those of heart disease, pneumonia, and liver disease among women. When all major preventable causes of death were analyzed simultaneously in a regression model, the coefficients of determination were 0.738 and 0.425 among men and women, respectively., Conclusions: Our findings suggest that local governments should prioritize preventing cancer deaths via cancer screening and smoking cessation measures in health plans, with a special focus on men., Competing Interests: None, (Copyright © Japan Medical Association.)

Background: We investigated the relationship between characteristic geriatric symptoms and healthy life expectancy in older adults in Japan. Additionally, we determined relationship predictors that would help formulate effective approaches toward promoting healthy life expectancy., Methods: The Kihon Checklist was used to identify older people at high risk of requiring nursing care in the near future. We evaluated the association of geriatric symptoms with healthy life expectancy while considering risk factors (frailty, poor motor function, poor nutrition, poor oral function, confinement, poor cognitive function, and depression). Data from the 2013 and 2019 Japan Gerontological Evaluation Studies were used. Healthy life expectancy was assessed using the multistate life table method., Results: Overall, 8,956 individuals were included. For both men and women, healthy life expectancy was shorter in the symptomatic group than in the asymptomatic group for several domains of the Kihon Checklist. For men, the difference between individuals with risk factors and those with no risk factors was the maximum for confinement (3.83 years) and the minimum for cognitive function (1.51 years). For women, the difference between individuals with risk factors and those with no risk factors was the maximum for frailty (4.21 years) and the minimum for cognitive function (1.67 years). Healthy life expectancy tended to be shorter when the number of risk factors was higher. Specifically, the difference between individuals with ≥3 risk factors and those with no risk factors was 4.46 years for men and 5.68 years for women., Conclusions: Healthy life expectancy was negatively associated with characteristic geriatric symptoms, with strong associations with frailty, physical functional decline, and depression. Therefore, comprehensive assessment and prevention of geriatric symptoms may increase healthy life expectancy.

Objective: Cardiac rehabilitation (CR) is effective in patients with acute coronary syndrome (ACS); however, CR programmes have not been fully implemented. This study aimed to reveal the current practice of outpatient CR and the dose-effect relationship of CR in real-world settings., Methods: We performed a nationwide retrospective cohort study using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Patients with ACS who underwent percutaneous coronary intervention between April 2014 and March 2018 were included. We analysed the implementation rate and dose of outpatient CR and the association between dose and outcomes., Results: Out of 202 320 patients who underwent percutaneous coronary intervention for ACS, a total of 20 444 (10%) underwent outpatient CR. The median (IQR) number of total CR sessions was 9 (3-17), and the median (IQR) duration for each session was 60 (42-60) min. Patients were divided into four groups according to the total number of sessions (≤9 times or ≥10 times) and the duration per session (<50 min or ≥50 min). Compared with the low-number/short-duration group, the adjusted HR for all-cause mortality was 1.00 (95% CI 0.80 to 1.24, p=0.97) in the low-number/long-duration group, 0.63 (95% CI 0.46 to 0.87, p=0.005) in the high-number/short-duration group and 0.74 (95% CI 0.60 to 0.92, p=0.008) in the high-number/long-duration group, respectively., Conclusion: We found that the participation rate for outpatient CR after ACS was low and the doses of sessions vary in real-world settings. A higher number of total sessions of outpatient CR is associated with a better prognosis irrespective of the session's duration., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: Although cardiac rehabilitation (CR) is a strongly recommended therapy, no large study has assessed the effects of outpatient CR in patients with heart failure (HF) in real-world settings. Therefore, this study aimed to investigate the multifactorial effects of outpatient CR in patients with HF using a nationwide database., Methods and Results: This nationwide retrospective cohort study was performed using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Patients with acute HF who underwent inpatient CR between April 2014 and March 2020 were included. The association between outpatient CR participation and all-cause mortality, rehospitalisation for HF, use of medical resources, and medical costs was analysed using propensity score matching analysis. Of 250,528 patients, 17,884 (7.1%) underwent outpatient CR. After propensity score matching, the CR (+) group was associated with a reduction in the risk of all-cause mortality (hazard ratio [HR]: 0.64, 95% confidence interval [CI]: 0.60-0.68, p < 0.001) and rehospitalisation for HF compared to the CR (-) group (HR: 0.87, 95% CI: 0.82-0.92, p < 0.001). The proportion of guideline-based medication use for HF at 1 year was higher in the CR (+) group than in the CR (-) group. The total medical costs from the index hospitalisation to 1.5 years after admission were similar between the groups., Conclusion: Outpatient CR participation after discharge from HF was associated with reduced mortality and rehospitalisation for HF without increasing medical costs., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Real-world evidence about heart failure (HF) medical care for elderly patients is limited. The aim of this study was to clarify the age-dependent associations of HF medications at discharge with clinical outcomes in a super-aged society using a real-world big database., Methods and Results: Patients hospitalized with a first episode of acute HF in 2013-2019 were identified in a nationwide claims database in Japan and were analyzed based on the HF medications at discharge. Hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) for clinical outcomes were calculated after adjustment. Among 325,468 patients from 4351 hospitals, 130,230 (40.0 %) were aged ≥ 85 years. All-cause mortality and HF readmission rate within 1 year were 14 % and 23 %, respectively. β-Blockers and angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers (ACEI/ARB) uses were associated with lower mortality (HR [95 %CI]: 0.84 [0.83,0.86] and 0.73 [0.71,0.74], respectively) and HF readmission (0.98 [0.97,0.99] and 0.89 [0.88,0.90], respectively). The associations were attenuated as the age increased and, in β-blockers use, the favorable associations with mortality and HF readmission were not observed in patients with ≥ 95 years and ≥ 80 years, respectively. In contrast, mineralocorticoid receptor antagonists (MRA) use was associated only with lower HF readmission (0.83 [0.82,0.84]), which was not attenuated with increased age., Conclusions: The favorable associations of β-blockers and ACEI/ARB uses with mortality and HF readmission were age-dependently attenuated in patients across a broad spectrum of HF in a super-aged society. In contrast, positive impact of MRA use on HF readmission was not attenuated with aging., Competing Interests: Conflict of interest statement The authors have no competing interests to declare., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: There is a lack of recent data reflecting the actual use of sodium-glucose cotransporter-2 (SGLT2) inhibitors for heart failure (HF) and type 2 diabetes (DM) in the superaged society. The present study investigated the association between the use of SGLT2 inhibitors and one-year prognosis in patients hospitalized across a broad spectrum of HF patients with DM in the superaged society using the Nationwide Electric Health Database in Japan., Methods: The patients hospitalized with the first episode of acute HF were identified from the National Database of Health Insurance Claims and Specific Health Checkups of Japan between April 2014 and March 2019. A cohort of 2,277 users of SGLT2 inhibitors and 41,410 users of the active comparator, dipeptidyl peptidase-4 (DPP4) inhibitors were compared. A propensity score-matched cohort study of 2,101 users of each inhibitor was also conducted. A multivariable multilevel mixed-effects survival model was conducted with adjustments, and hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated., Results: Among 300,398 patients discharged with HF in 4,176 hospitals, 216,016 (71.9%) were 75 years or older, and 60,999 (20.3%) took antidiabetic medications. Among them, the patients treated with SGLT2 inhibitors were younger and had a more severe status than those treated with DPP4 inhibitors. Kaplan-Meier analysis showed that patients treated with SGLT2 inhibitors had a lower mortality risk and HF readmission. In propensity-matched cohorts, SGLT2 inhibitor use was associated with a lower risk of mortality and HF readmission than DPP-4 inhibitor use (HR [95% CI]; 0.70 [0.56, 0.89] and 0.52 [0.45, 0.61], respectively). Very elderly (≥ 75 years) patients showed similar results. Favorable effects were also observed across all age groups, including ≥ 75 years, in patients with coronary artery disease or atrial fibrillation and with concomitant β-blocker, diuretics, or insulin., Conclusion: The use of SGLT2 inhibitors at discharge was associated with a lower risk of one-year mortality and HF readmission in patients across a broad spectrum of HF with DM in the superaged society. The findings further support the benefits of using SGLT2 inhibitors in very elderly HF care and complement the current evidence., (© 2022. The Author(s).)

This study clarified the age of death in patients with or without diabetes using the largest health insurance database in Japan. This population-based retrospective cohort study was performed using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) data. The ages of death between people with and without diabetes were compared. A total of 142,277,986 patients (74,488,962 women and 67,789,024 men) over 6 years, including 4,647,016 females, and 6,507,817 males with diabetes, were included. 2,786,071 females and 2,975,876 males died over 6 years, including 652,699 females and 954,655 males with diabetes. The average age of death in patients with diabetes was 2.6 years less than that of patients without diabetes. This descriptive epidemiological study illustrated the difference in age at death of patients with and without diabetes., (© 2022 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: Adrenaline is the first-line medication for managing anaphylaxis. A better understanding of prescription trends for adrenaline auto-injectors (AAIs) is important to improving patient care as well as information on health education interventions and medical guidelines. However, it has been difficult to gather comprehensive data in a sustainable manner. Thus, we aimed to investigate trends in AAI prescriptions in Japan., Methods: We searched the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), a unique and comprehensive database of health insurance claims, and investigated prescriptions for AAIs for all ages (April 2017 to March 2018). We assessed the annual number of prescriptions per person as well as prescription rates per 100,000 population per year by age, sex, and geographic region., Results: A total of 88,039 subjects (56,109 males, 31,930 female) and 116,758 devices (1.33 AAIs per patient per year) were prescribed AAIs at least once a year for all ages. The prescription rate for AAIs was 69.5 per 100,000 population-years. Patients aged 0-9 years were prescribed AAIs at the rate of 278.9 per 100,000 population-years. Patients aged 0-19 years were 6.4 times more likely to be prescribed AAIs than those over 20 years of age. Males were more frequently prescribed AAIs than females in all age groups, except for those aged 20-24 years. We also evaluated differences in prescription rates by geographic region., Conclusions: This comprehensive evaluation revealed trends in AAI prescriptions, thus helping develop preventive strategies with respect to anaphylaxis in Japan., (Copyright © 2022 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Introduction: The appropriate hospital case volume for catheter ablation (CA) in patients with atrial fibrillation (AF) according to the ablation technology has not been fully examined. This study aimed to investigate the association between the hospital case volume for AF and periprocedural complications and AF recurrence., Methods: In this retrospective cohort study, we used data from the National Database of Health Insurance Claims and Specific Health Checkups, which covers almost all healthcare insurance claims data in Japan. We included patients with AF who underwent first-time CA from April 2014 to March 2020. Using mixed-effect logistic regression, we analyzed the effect of the annual case volume for AF ablation on acute periprocedural complications and 1-year success rate off antiarrhythmic drugs according to the ablation technology (radiofrequency ablation or cryoballoon ablation)., Results: Among 270 116 patients, 207 839 (77%) patients underwent radiofrequency ablation and 56 648 (21%) patients underwent cryoballoon ablation. Of all patients, acute complications occurred in 5411 (2.0%) patients, and the recurrence at 1 year was 71 511 (27%). In the radiofrequency ablation group, acute complications and 1-year AF recurrence according to case volume decreased as the annual case volume increased to up to 150-200 cases/year. However, in the cryoballoon ablation group, these outcomes were similar regardless of the case volumes., Conclusion: The case-volume effect was noted in the radiofrequency ablation group, but not in the cryoballoon ablation group. Our results may affect the selection of ablation technology, especially in smaller case-volume hospitals., (© 2022 Wiley Periodicals LLC.)

Severe UV exposure induces skin inflammation, causing erythema. Lycii Fructus ( Lycium barbarum and Lycium chinense ) is a potential antioxidant agent with a high content of polyphenols, including rutin and chlorogenic acid. This study examined the effects of Lycii Fructus extract (LFE) on UVB-induced skin erythema in humans. Healthy volunteers were randomly assigned to one of two groups and received UVB irradiation at 1.5 minimal erythemal dose (MED) on day 0 at three designated sites on their backs, and the skin color was measured until day 7. After an 8-week treatment with LFE (900 mg/day) or placebo, UVB irradiation (l.5 MED) was applied again at different sites on day 63. Skin color was continuously measured in each group until day 69. LFE tablet administration for 8 weeks significantly inhibited UVB-induced erythema formation and increased the MED by 13%. Erythema formation peaked on the first day after UVB irradiation, but gradually dissipated over the next several days. LFE tended to accelerate erythema disappearance. To determine the polyphenol responsible for the protection against UVB-induced skin damage, the effects of LFE-derived polyphenols and their metabolites on UVB-induced cytotoxicity were examined in vitro . The major intestinal metabolite of rutin and LFE significantly attenuated phototoxicity and in human keratinocyte HaCaT cells. Quercetin enhanced intracellular glutathione levels in HaCaT cells, even though LFE did not increase it. Together, the results showed that LFE inhibited erythema formation and accelerated erythema dissipation, possibly through its direct antioxidative action., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Tsunenaga et al.)

Background: The survival rate of chronic dialysis patients in Japan remains the highest worldwide, so there is value in presenting Japan's situation internationally. We examined whether aggregate figures on dialysis patients in the National Database of Health Insurance Claims and Special Health Checkups of Japan (NDB), which contains data on insured procedures of approximately 100 million Japanese residents, complement corresponding figures in the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR)., Methods: Subjects were patients with medical fee points for dialysis recorded in the NDB during 2014-2018. We analyzed annual numbers of dialysis cases, newly initiated dialysis cases- and deaths., Results: Compared with the JRDR, the NDB had about 6-7% fewer dialysis cases but a similar number of newly initiated dialysis cases. In the NDB, the number of deaths was about 6-10% lower, and the number of hemodialysis cases was lower, while that of peritoneal dialysis cases was higher. The cumulative survival rate at dialysis initiation was approximately 6 percentage points lower in the NDB than in the JRDR, indicating that some patients die at dialysis initiation. Cumulative survival rate by age group was roughly the same between the NDB and JRDR in both sexes., Conclusion: The use of the NDB enabled us to aggregate data of dialysis patients. With the definition of dialysis patients used in this study, analyses of concomitant medications, comorbidities, surgeries, and therapies will become possible, which will be useful in many future studies., (© 2021. The Author(s).)

Aims/introduction: We assessed the association between dipeptidyl peptidase-4 inhibitors (DPP-4is) and bullous pemphigoid (BP) and time-dependent changes in the risk for developing BP after DPP-4i initiation., Materials and Methods: The present population-based, real-world study was carried out using the Japanese National Database dataset collected between 2013 and 2018. To assess independent correlations between DPP-4is and the development of BP, the self-controlled case series method was used., Results: Among the cohort followed up for a median of 1,540 days, 53,027 patients were likely to develop BP. The possible incidence rate of BP in all 150,328,339 patients was 10.4/100,000 person-years. Among the 9,705,814 patients with type 2 diabetes, 15,634 were likely to develop BP. The possible incidence rate of BP in patients with type 2 diabetes was 38.1/100,000 person-years, whereas that in patients with type 2 diabetes who did and did not use DPP-4is was 40.7 and 30.0/100,000 person-years, respectively. Analysis of the 28,705 patients with type 2 diabetes likely to develop BP after initial DPP-4i use showed a risk ratio of 2.15 (95% confidence interval [CI] 1.75-2.63), 1.70 (95% CI 1.37-2.11), 1.44 (95% CI 1.15-1.82), 1.25 (95% CI 0.98-1.59), 0.84 (95% CI 0.63-1.10), 0.84 (95% CI 0.64-1.11) and 1.05 (95% CI 0.92-1.20), for the risk period of ≤30, 31-60, 61-90, 91-120, 121-150, 151-180 and 181-365 days, respectively., Conclusions: Although DPP-4is were associated with increased risk for BP, the risk was particularly significant within 3 months from first use., (© 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Aldehyde dehydrogenases (ALDHs) are the major enzyme superfamily for the aldehyde metabolism. Since the ALDH polymorphism leads to the accumulation of acetaldehyde, we considered that the enhancement of the liver ALDH activity by certain food ingredients could help prevent alcohol-induced chronic diseases. Here, we evaluated the modulating effects of 3-hydroxyphenylacetic acid (OPAC), the major metabolite of quercetin glycosides, on the ALDH activity and acetaldehyde-induced cytotoxicity in the cultured cell models. OPAC significantly enhanced the total ALDH activity not only in mouse hepatoma Hepa1c1c7 cells, but also in human hepatoma HepG2 cells. OPAC significantly increased not only the nuclear level of aryl hydrocarbon receptor (AhR), but also the AhR-dependent reporter gene expression, though not the nuclear factor erythroid-2-related factor 2 (Nrf2)-dependent one. The pretreatment of OPAC at the concentration required for the ALDH upregulation completely inhibited the acetaldehyde-induced cytotoxicity. Silencing AhR impaired the resistant effect of OPAC against acetaldehyde. These results strongly suggested that OPAC protects the cells from the acetaldehyde-induced cytotoxicity, mainly through the AhR-dependent and Nrf2-independent enhancement of the total ALDH activity. Our findings suggest that OPAC has a protective potential in hepatocyte models and could offer a new preventive possibility of quercetin glycosides for targeting alcohol-induced chronic diseases.

Aims/introduction: The purpose of the present study was to quantify errors in the diagnosis of diabetes for use in the national database, using a sufficient population size., Materials and Methods: A claims database constructed by the JMDC (Tokyo, Japan), using standardized disease classifications and anonymous record linkage, was used in this validation study. We included patients with health insurance claims data from April 2005 to March 2019 in the JMDC claims database. We excluded patients without a record of specific health checkups in Japan. Sample size calculation was based on a 5% prevalence of diabetes and 0.4% absolute accuracy (i.e., 1,250,000 individuals), to calculate the sensitivity, specificity, positive predictive value and negative predictive value., Results: In total, 2,999,152 patients were included in this study, of which 165,515 were classified as having diabetes based on specific health checkups (validation cohort prevalence of 5.5%). The newly devised algorithm had three elements - the diagnosis-related codes for diabetes without suspected flag, the medication codes for diabetes and then these two codes on the same record - and yielded a sensitivity of 74.6%, positive predictive value of 88.4% and Kappa Index of 0.80 (the highest values)., Conclusions: In future claims database studies, our validated algorithms will be useful as diagnostic criteria for diabetes., (© 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Importance: Although research has shown that centenarians tend to experience shorter periods of serious illness compared with other age groups, few studies have focused on the medical expenditures of centenarians as a potential indicator of the scale of medical resources used in their last year of life., Objective: To compare Japanese centenarians' and noncentenarians' monthly medical expenditures during the year before death according to age and sex., Design, Setting, and Participants: This retrospective cohort study used linked national health and long-term care insurance data collected from April 2013 to March 2018 in Nara Prefecture, Japan, for residents aged 75 years or older who were insured under the Medical Care System for older adults and died between April 2014 and March 2018. Data were analyzed from April 2013 to March 2018., Exposures: Age of 100 years or older (centenarians) vs 75 to 99 years (noncentenarians)., Main Outcomes and Measures: The numbers of unique inpatients and outpatients and medical expenditures related to decedents' hospitalization and outpatient care were extracted and analyzed based on sex and age group. The Jonckheere-Terpstra test was used to identify trends in unadjusted medical expenditures by age group, and generalized estimating equations were used to estimate monthly median expenditures by age group with adjustment for comorbidity burden and functional status., Results: Of 34 317 patients aged 75 to 109 years (16 202 men [47.2%] and 18 115 women [52.8%]) who died between April 2014 and March 2018, 872 (2.5%) were aged 100 to 104 years (131 men [15.0%] and 741 women [85.0%]) and 78 (0.2%) were aged 105 to 109 years (fewer than 10 were men). The analysis of unadjusted medical expenditures in the last year of life showed a significant trend of lower expenditures for the older age groups; the median adjusted total expenditures during the 30 days before death by age group were $6784 (IQR, $4884-$9703) for ages 75 to 79 years, $5894 (IQR, $4292-$8536) for 80 to 84 years, $5069 (IQR, $3676-$7150) for 85 to 89 years, $4205 (IQR, $3085-$5914) for 90 to 94 years, $3522 (IQR, $2626-$4861) for 95 to 99 years, $2898 (IQR, $2241-$3835) for 100 to 104 years, and $2626 (IQR, $1938-$3527) for 105 to 109 years. The proportion of inpatients among all patients in the year before death also decreased with increasing age: 4311 of all 4551 patients aged 75 to 79 years (94.7%); 43 of all 78 patients aged 105 to 109 years (55.1%); 2831 of 2956 men aged 75 to 79 years (95.8%); 50.0% of men aged 105 to 109 years (the number is not reported owing to the small sample size); 1480 of 1595 women aged 75 to 79 years (92.8%); and 55.7% of women aged 105 to 109 years (the number of women is not reported to prevent back-calculation of the number of men). Specifically, 274 of 872 patients aged 100 to 104 years (31.4%) and 35 of 78 patients aged 105 to 109 years (44.9%) had not been admitted to a hospital in the year before death., Conclusions and Relevance: This cohort study found that medical expenditures in the last year of life tended to be lower for centenarians than for noncentenarians aged 75 years or older in Japan. The proportion of inpatients also decreased with increasing age. These findings may inform future health care services coverage and policies for centenarians.

Aim: This study aimed to determine whether there is an association between influenza and new-onset type 1 diabetes., Materials and Methods: This population-based retrospective cohort study used data from the National Database of Health Insurance Claims and Specific Health Check-ups of Japan. Influenza was defined based on drug prescriptions and the onset of type 1 diabetes was defined using specific medical codes indicating a diagnosis of type 1 diabetes. The incidence rate ratio of new-onset type 1 diabetes within 180 days after an influenza diagnosis was calculated and it was compared with that at other times using Poisson regression and generalized estimating equations. Sensitivity analyses were performed to confirm the robustness of this finding., Results: The data of 10,400 patients with new-onset type 1 diabetes were analyzed, including 2,196 (952 male 1,244 female) patients diagnosed with influenza between 1 September 2014 and 31 August 2017. Although only patients with type 1 diabetes were included, adjusted analysis showed that individuals had a 1.3-fold (95% confidence interval: 1.15-1.46) higher risk of developing type 1 diabetes in the first 180 days after influenza diagnosis than that at other times., Conclusions: In this Japanese population-based cohort, the risk of new-onset type 1 diabetes may increase after the diagnosis of influenza. These results, which must be confirmed in other populations, suggest that influenza may be a causal factor for new-onset type 1 diabetes. The molecular mechanisms underlying the potential etiological relationship between influenza and type 1 diabetes should be elucidated., (© 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Introduction: This study was conducted to investigate the incidence and time trend of lower limb amputation (LLA) among people with and without diabetes., Research Design and Methods: This retrospective population-based cohort study was based on the national claims data in Japan, comprising a total population of 150 million. Data of all individuals who had LLA from April 2013 to March 2018 were obtained. We analysed the sex-adjusted and age-adjusted annual LLA rate (every fiscal year) in people with and without diabetes for major and minor amputation. To test for time trend, Poisson regression models were fitted., Results: In the 5-year period, 30 187 major and 29 299 minor LLAs were performed in Japan. The sex-adjusted and age-adjusted incidence of major and minor LLAs was 9.5 (people with diabetes, 21.8 vs people without diabetes, 2.3, per 100 000 person-years) and 14.9 (people with diabetes, 28.4 vs people without diabetes, 1.9, per 100 000 person-years) times higher, respectively, in people with diabetes compared with those without. A significant decline in the annual major amputation rate was observed (p<0.05) and the annual minor amputation rate remained stable (p=0.63) when sex, age and people with and without diabetes were included as dependent variables., Conclusions: This is the first report of the national statistics of LLAs in Japan. The incidence of major and minor LLAs was 10 and 15 times higher, respectively, in people with diabetes compared with those without. A significant decline in the major amputation rate was observed, and the annual minor amputation rate remained stable during the observation period. This information can help to create an effective national healthcare strategy for preventing limb amputations, which affect the quality of life of patients with diabetes and add to the national healthcare expenditure., Competing Interests: Competing interests: YN received consultant fees from Novo Nordisk. SO received speaker fees from Novo Nordisk, Mitsubishi Tanabe, Sumitomo Dainippon, Arkray, Bayer, Eli Lilly, Boehringer Ingelheim, Ono, AstraZeneca, Sanofi and Takeda, outside of the submitted work. YA received lecture fees and consultant fees from MSD KK, Ono, Otsuka, Sumitomo Dainippon, Daiichi Sankyo, Eli Lilly, Sanofi S.A., Chugai, Novo Nordisk, Kissei, Nippon Boehringer Ingelheim, Astellas, Kyowa Hakko Kirin, Pfizer, Takeda, Mitsubishi Tanabe, Novartis, Janssen Pharmaceutical K.K, Japanese Red Cross Society Nara Red Cross Blood Center, Sumitomo Dainippon, Kissei. HI received lecture fees and consultant fees from Takeda, Eli Lilly Japan, Sanofi, Merck & Co., Astellas, Mitsubishi Tanabe, Daiichi Sankyo, Ono, AstraZeneca, Taisho Toyama, Shionogi, Kowa, Boehringer Ingelheim, Novo Nordisk, Sumitomo Dainippon, and Kyowa Hakko Kirin. YT received consultant fees from Novo Nordisk, Otsuka, and Recordati and speaker fees from Novo Nordisk, Sumitomo Dainippon, Eli Lilly, Ono, Novartis, Nippon Boehringer Ingelheim, AstraZeneca and Kyowa Kirin. The other authors declare that they have no conflict of interest., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The relationship between public health expenditure and number of teeth was investigated in patients with diabetes mellitus using data obtained from the Japanese National Database of Health Insurance Claims and Specific Health Checkups. Data on medical, dental, and pharmacy claims generated between April 2015 and March 2016 were analyzed in patients with diabetes mellitus aged 50-74 years who used outpatient services during this period. Patients initiating medical and pharmacy claims related to diabetes mellitus were defined as having diabetes mellitus. Number of teeth was defined as number of teeth in conjunction with periodontitis due to the nature of the data source. Descriptive statistics were used to investigate the association between number of teeth and public health expenditure. Data on a total of 1,017,758 patients with diabetes mellitus were analyzed. Patients with the fewest teeth incurred higher medical expenses. The largest mean difference in medical expenditure was observed between patients with 5-9 teeth and those with over 28 teeth. The results of this study suggest that public health expenditure on patients with diabetes mellitus differs based on number of teeth.