Oral anticoagulation after atrial fibrillation catheter ablation: benefits and risks.

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.

Novel subgroups of obesity and their association with outcomes: a data-driven cluster analysis.

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/m2) 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.

Validity of Diagnostic Algorithms for Cardiovascular Diseases in Japanese Health Insurance Claims.

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.

The impact of hospital case volume on the outcomes after catheter ablation for atrial fibrillation according to the ablation technology.

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.

Contemporary use of SGLT2 inhibitors in heart failure patients with diabetes mellitus: a comparison of DPP4 inhibitors in a nationwide electric health database of the superaged society.

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 ß-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.

Rehabilitation services and related health databases, Japan.

The demographic transition towards an ageing population and the epidemiological transition from communicable to noncommunicable diseases have increased the demand for rehabilitation services globally. The aims of this paper were to describe the integration of rehabilitation into the Japanese health system and to illustrate how health information systems containing real-world data can be used to improve rehabilitation services, especially for the ageing population of Japan. In addition, there is an overview of how evidence-informed rehabilitation policy is guided by the analysis of large Japanese health databases, such as: (i) the National Database of Health Insurance Claims and Specific Health Checkups; (ii) the long-term care insurance comprehensive database; and (iii) the Long-Term Care Information System for Evidence database. Especially since the 1990s, the integration of rehabilitation into the Japanese health system has been driven by the country's ageing population and rehabilitation is today provided widely to an increasing number of older adults. General medical insurance in Japan covers acute and post-acute (or recovery) intensive rehabilitation. Long-term care insurance covers rehabilitation at long-term care institutions and community facilities for older adults with the goal of helping to maintain independence in an ageing population. The analysis of large health databases can be used to improve the management of rehabilitation care services and increase scientific knowledge as well as guide rehabilitation policy and practice. In particular, such analyses could help solve the current challenges of overtreatment and undertreatment by identifying strict criteria for determining who should receive long-term rehabilitation services.

Tant la transition démographique vers un vieillissement de la population que la transition épidémiologique des maladies transmissibles vers les maladies non transmissibles ont entraîné une augmentation de la demande en services de réadaptation dans le monde. Le présent document poursuit plusieurs objectifs: décrire l'intégration de la réadaptation dans le système de santé au Japon, et illustrer comment les systèmes de santé contenant des données réelles peuvent être utilisés en vue d'améliorer de tels services, en particulier pour une population nipponne vieillissante. En outre, il offre un aperçu de la manière dont la politique de réadaptation étayée par des faits s'inspire de l'analyse de vastes bases de données sanitaires japonaises, parmi lesquelles: (i) la base de données nationale des demandes de remboursement au titre de l'assurance-maladie et des bilans de santé spécifiques; (ii) la base de données complète de l'assurance pour les soins longue durée; et enfin, (iii) la base de données du système d'information relatif aux attestations de soins longue durée. Le vieillissement de la population a poussé le Japon à inclure la réadaptation dans son système de santé, surtout depuis les années 1990; aujourd'hui, un nombre croissant de personnes âgées ont aisément accès à des services de réadaptation. Au Japon, l'assurance-maladie globale prend en charge la réadaptation intensive aiguë et post-aiguë (ou de rétablissement). De son côté, l'assurance pour les soins longue durée couvre la réadaptation dans les établissements dédiés et les infrastructures collectives accueillant des personnes âgées, avec pour but de contribuer à préserver l'autonomie au sein d'une population vieillissante. L'analyse de vastes bases de données sanitaires peut favoriser une meilleure gestion des services de réadaptation et accroître les connaissances scientifiques, mais aussi orienter les politiques et pratiques en la matière. Ce type d'analyse peut surtout aider à s'attaquer aux enjeux actuels que représentent les traitements excessifs ou insuffisants, en identifiant des critères stricts permettant de déterminer qui doit faire l'objet d'une réadaptation sur le long terme.

La transición demográfica hacia el envejecimiento de la población y la transición epidemiológica de las enfermedades transmisibles a las no transmisibles han aumentado la demanda de servicios de rehabilitación en todo el mundo. Los objetivos de este artículo son describir la integración de la rehabilitación en el sistema sanitario japonés e ilustrar cómo los sistemas de información sanitaria que contienen datos del mundo real se pueden utilizar para mejorar los servicios de rehabilitación, en especial para la población que envejece en Japón. Además, se ofrece una visión general de cómo la política de rehabilitación fundamentada en la evidencia se guía por el análisis de las grandes bases de datos sanitarias japonesas, como: (i) la Base de Datos Nacional de Reclamaciones al Seguro de Enfermedad y Chequeos Médicos Específicos; (ii) la base de datos integral del seguro de cuidados de larga duración; y (iii) la base de datos del Sistema de Información de Cuidados de Larga Duración para la Evidencia. En particular, desde la década de 1990, la integración de la rehabilitación en el sistema sanitario japonés se ha visto impulsada por el envejecimiento de la población del país y, en la actualidad, la rehabilitación se ofrece de forma generalizada a una cantidad cada vez mayor de adultos mayores. El seguro médico general de Japón cubre la rehabilitación intensiva aguda y posaguda (o de recuperación). El seguro de cuidados de larga duración cubre la rehabilitación en instituciones de larga estancia y centros comunitarios para adultos mayores con el objetivo de ayudar a mantener la independencia en una población que envejece. El análisis de las grandes bases de datos sanitarias puede servir para mejorar la gestión de los servicios de atención a la rehabilitación y aumentar los conocimientos científicos, así como para orientar la política y la práctica de la rehabilitación. En concreto, estos análisis podrían ayudar a resolver los problemas actuales de sobretratamiento y subtratamiento, al identificar criterios estrictos para determinar quién debe recibir servicios de rehabilitación de larga duración.

Trends and Factors Associated With Cardiac Rehabilitation Participation　- Data From Japanese Nationwide Databases.

BACKGROUND: Few studies have comprehensively evaluated the trends and factors associated with CR participation across major cardiovascular diseases in Japan.Methods and Results: This study performed a nationwide cross-sectional study using the National Database of Health Insurance Claims and Specific Health Checkups of Japan and the Japanese Registry of All Cardiac and Vascular Diseases and the Diagnosis Procedure Combination database. This study described the nationwide trends and evaluated patient- and hospital-level associated factors of CR participation for patients with acute heart failure (AHF), acute coronary syndrome (ACS), acute aortic dissection (AAD), peripheral artery disease (PAD), and after cardiovascular surgery using mixed-effect logistic regression analysis. Although the annual number of patients who underwent CR has increased during the study period, the total number of patients participating in outpatient CR was lower than that of inpatient CR. The outpatient CR participation rate was lower for patients with AHF (3.5%), AAD (3.2%), and PAD (1.7%), compared with ACS (7.9%) and after surgery (9.4%). Age, sex, body mass index, Barthel index, Charlson comorbidity index, and institutional capacity were identified as significant associated factors of CR participation in inpatient and outpatient settings. CONCLUSIONS: Participation in outpatient CR was still low, and higher age, multi-comorbidity, and low institutional capacity contributed to the lower outpatient CR participation rate. Identification of the associated factors may help cardiologists to increase CR participation.

Tracing all patients who received insured dialysis treatment in Japan and the present situation of their number of deaths.

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.

Evaluation of adrenaline auto-injector prescription profiles: A population-based, retrospective cohort study within the National Insurance Claims Database of Japan.

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.

Factors associated with viral clearance periods from patients with COVID-19: A retrospective observational cohort study.

INTRODUCTION: Knowledge is limited on the virologic course of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, particularly the time taken for viral clearance and the optimal time to discontinue isolation. This study aims to identify the clinical and demographic factors influencing the time taken for viral clearance in patients with COVID-19 to determine the optimal isolation period. METHODS: This two-center retrospective observational cohort study was conducted between March 1 and June 31, 2020. Patients with COVID-19, which was confirmed by real-time reverse transcription polymerase chain reaction, were included. Data were extracted from medical records. The positive duration, which was defined as the period from the day of symptom onset to the negative conversion day, was assessed using a generalized linear model. RESULTS: We included 63 patients. The mean positive duration was 20 days. The positive duration was significantly shorter for patients younger than 30 years of age and those between 30 and 60 years of age than for patients older than 60 years of age. We observed a more scattered distribution of the positive duration in older patients than in younger patients. CONCLUSIONS: Younger patients who recovered from COVID-19 took less time to clear SARS-CoV-2 than older patients; thus, a classification of the isolation periods based on age could be considered. A uniform viral clearance period for older patients may be difficult to determine because of biases such as underlying medical conditions. Further surveillance measures are recommended to determine the viral clearance time and the optimal isolation period.

Long-term prognosis of enteral feeding and parenteral nutrition in a population aged 75 years and older: a population-based cohort study.

BACKGROUND: Enteral feeding and parenteral nutrition (PN) using gastrostomy (GS) and a nasogastric tube feeding (NGT) and PN should be initiated for older patients based on their prognoses. This study aimed to investigate the long-term prognosis of patients aged ≥75 years who underwent enteral feeding via GS and NGT as well as PN. METHODS: A population-based cohort study was conducted using Japan's universal health insurance claims in the Nara Prefecture. This study enrolled 3,548 patients aged ≥75 years who received GS (N=770), NGT (N=2,370), and PN (N=408) during hospital admissions between April 2014 and March 2016. The GS group was further categorized into secondary GS (N=400) with preceding NGT or PN within 365 days and primary GS (N=370) without preceding NGT or PN groups. In the secondary GS group, 356 (96%) patients received NGT (versus PN). The outcome was mortality within 730 days after receiving GS, NGT, and PN. Cox regression analyses in cases with or without malignant diseases, adjusted for sex, age, comorbidity, and hospital type, were performed to compare mortality in the groups. RESULTS: Of the 3,548 participants, 2,384 (67%) died within 730 days after the initiation of GS and NGT and PN. The 2-year mortality rates in the secondary GS, primary GS, NGT, and PN groups were 58%, 66%, 68%, and 83% in patients without malignancies and 67%, 71%, 74%, and 87% in those with malignancies, respectively. In the non-malignant group, Cox regression analysis revealed that secondary GS (hazard ratio (HR) = 0.43, 95% CI: 0.34-0.54), primary GS (HR = 0.51, 95% CI: 0.40-0.64), and NGT (HR = 0.71, 95% CI: 0.58-0.87) were statistically significantly associated with lower mortality compared with PN. CONCLUSIONS: Approximately 58% to 87% patients aged ≥75 years died within 730 days after initiation of nutrition through GS, NGT, or PN. Patients with non-malignant diseases who received secondary GS exhibited better 2-year prognosis than those who received NGT or PN. Healthcare professionals should be aware of the effectiveness and limitations of enteral feeding and PN when considering their initiation.

Evaluation of Public Health Expenditure by Number of Teeth among Outpatients with Diabetes Mellitus.

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.

Discontinuation of etanercept after achievement of sustained remission in patients with rheumatoid arthritis who initially had moderate disease activity-results from the ENCOURAGE study, a prospective, international, multicenter randomized study.

OBJECTIVES: To investigate the efficacy and safety of etanercept (ETN) in patients with rheumatoid arthritis (RA) with moderate disease activity and the possibility to discontinue ETN after achieving remission. METHODS: Multicenter, randomized, and open-label study was conducted in Japan and Korea. RA patients (disease duration <5 years) with moderate disease activity despite methotrexate (MTX) treatment were allocated to either MTX or ETN + MTX (Period 1) for 12 months. Patients who achieved sustained remission defined as DAS28 < 2.6 at both 6 and 12 months in the ETN + MTX group, were randomized to either continue or discontinue ETN for 12 months (Period 2). RESULTS: A total of 222 patients were enrolled in Period 1 and clinical remission was achieved in 106/157 (67.5%) and 5/28 (17.9%) patients in the ETN + MTX and MTX groups, respectively. In Period 2, sixty-seven patients were randomized and finally 28/32 (87.5%) and 15/28 (53.6%) patients who continued or discontinued ETN maintained clinical remission. Baseline disease activity and the presence of comorbid diseases influenced the maintenance of remission after ETN discontinuation. CONCLUSIONS: ETN + MTX was efficient for RA patients with moderate disease activity into remission. After achieving sustained remission, a half of the patients who discontinued ETN could maintain remission for 1 year.

Web-based questionnaire survey for exploring engagement characteristics of advance care planning in Japan: a cross-sectional study.

OBJECTIVE: Definitive promotion of advance care planning (ACP) practices will require policy interventions tailored to the characteristics of the Japanese population and society. However, effective policies for promoting ACP are currently lacking in Japan. This study aimed to explore the characteristics of Japanese people who engaged in ACP activities through a web-based questionnaire survey, which was administered to individuals aged 25-64 years and classified into four occupational categories (non-medical/non-caregiving professionals [general population], physicians, nurses, and caregivers). RESULTS: The total sample size was 1,648, with equal occupational category and age group distributions. Respondents in the general population group were less likely to discuss or document ACP than those in the other groups. Stepwise logistic regression analysis showed a significant difference in the adjusted odds ratio (aOR) of the independent variables of "attended cardiopulmonary resuscitation (CPR) training session(s)" (aOR: 1.93; 95% confidence interval [CI]: 1.18-3.15) and "having experience in performing CPR" (aOR: 2.61; 95% CI: 1.51-4.54) for respondents who discussed ACP with their families. A significant difference was observed in the aOR of the independent variable of "having experience in performing CPR" (aOR: 4.58; 95% CI: 2.30-9.13) for respondents who documented a written record of ACP.

Insights from the trends of omalizumab and mepolizumab utilization in patients with asthma: A population-based cohort study using the National Database in Japan.

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.

Clinical impact of the intensity of follow-up cystoscopy in patients with high-risk non-muscle-invasive bladder cancer.

PURPOSE: There is significant lack on evidence regarding the effect of non-adherence to a recommended protocol in follow-up of high-risk non-muscle-invasive bladder cancer (NMIBC), or the impact of delaying detection of recurrent lesion. Here, we aimed to investigate the optimal frequency of follow-up cystoscopy of high-risk NMIBC with respect to oncological safety in the Japanese real-world clinical practice. METHODS: This retrospective single-center study included 206 patients with primary high-risk NMIBC. The intensity (%) of follow-up cystoscopy was calculated based on actual visits for cystoscopy and guideline-recommended frequency in the first 24-month follow-up period. Inverse probability of treatment weighting analyses was used to reduce the risk of bias between groups. We performed a restricted cubic spline analysis with knots at intensity of follow-up cystoscopy ≤ 100% group to examine the possible association of progression risk with the intensity of follow-up as a continuous exposure. RESULTS: The median intensity was 87.5% (interquartile range, 75-100). Adjusted multivariate analysis for MIBC-free and progression-free survival demonstrated no significant difference between adjusted ≤ 75% and > 75% intensity groups. A restricted cubic spline analysis suggested no significant effect of the intensity of follow-up on progression risk, and hazard ratios of patients of < 100% intensity were equivalent to those of patients of 100% intensity. CONCLUSION: Our finding suggested decreased intensity of follow-up cystoscopy did not affect oncological outcomes in patients with high-risk NMIBC. Further prospective trials directly aimed at investigating optimized follow-up schedules for NMIBC are mandatory before substantial changes to existing clinical guidelines.

Annual variation of estimated glomerular filtration rate in health check-ups associated with end-stage kidney disease.

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.

Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis.

Individuals with rheumatoid arthritis frequently have autoantibodies to citrullinated peptides, suggesting the involvement of the peptidylarginine deiminases citrullinating enzymes (encoded by PADI genes) in rheumatoid arthritis. Previous linkage studies have shown that a susceptibility locus for rheumatoid arthritis includes four PADI genes but did not establish which PADI gene confers susceptibility to rheumatoid arthritis. We used a case-control linkage disequilibrium study to show that PADI type 4 is a susceptibility locus for rheumatoid arthritis (P = 0.000008). PADI4 was expressed in hematological and rheumatoid arthritis synovial tissues. We also identified a haplotype of PADI4 associated with susceptibility to rheumatoid arthritis that affected stability of transcripts and was associated with levels of antibody to citrullinated peptide in sera from individuals with rheumatoid arthritis. Our results imply that the PADI4 haplotype associated with susceptibility to rheumatoid arthritis increases production of citrullinated peptides acting as autoantigens, resulting in heightened risk of developing the disease.

Research note changes in the number of outpatient visits in Japan during the COVID-19 pandemic.

OBJECTIVE: This study aimed to determine the change in the number of outpatient visits in Japan since the beginning of the COVID-19 pandemic, using data on the outpatient claims submitted by medical institutions to insurers in 2019 and 2020, from the National Database of Health Insurance Claims and Specific Health Check-ups. We calculated the total number of outpatient visits, and number of visits for individual diseases according to the International Classification of Diseases-10 codes on the claim form. RESULTS: The number of outpatient visits per million people decreased by 9.98% in 2020 compared to 2019. Of the diseases included in the analysis, 71 showed a decrease in the number of visits by ≥ 1%. There were significant decreases in the number of visits related to infectious diseases (influenza, acute bronchitis, and acute laryngitis, etc.), and chronic diseases (hemorrhoids, cystic kidney disease, dyspepsia, and chronic sinusitis, etc.). The observed decreased rate of outpatient visit might have been due to, a decrease in the incidence of disease, a decreased frequency of visit by patients with the disease, or both. Our analysis method using actual health insurance claim data can be applied worldwide, where researchers have access to national information on health insurance claims.

Antithyroid drug-induced leukopenia and G-CSF administration: a long-term cohort study.

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.