Average daily glucocorticoid dose, number of prescription days, and cumulative dose in the initial 90 days of glucocorticoid therapy are associated with subsequent hip and clinical vertebral fracture risk: a retrospective cohort study using a nationwide health insurance claims database in Japan.

PURPOSE: Fracture risk assessment is recommended at three months after glucocorticoid (GC) therapy initiation. This study aimed to assess whether GC exposure in the initial 90 days of GC therapy is associated with subsequent hip and clinical vertebral fracture risk using the nationwide health insurance claims database of Japan (NDBJ). METHODS: Patients aged ≥ 50 years who were prescribed GC (≥ 70 mg prednisolone or equivalent; PSL) in the initial 90 days of GC therapy and were followed for hip and clinical vertebral fracture incidences for the subsequent 1080 days were selected from NDBJ. Associations of GC exposure with hip or clinical vertebral fracture risk were evaluated by Cox regression analysis adjusted for potential confounders. RESULTS: We selected 316,396 women and 299,871 men for the GC-exposed group and 43,164 women and 33,702 men for the reference group. Higher GC doses and longer prescription days in the initial 90 days of GC therapy were significantly and dose-dependently associated with increased fracture risk relative to the reference group. Patients receiving GC ≥ 5 mg PSL/day had a significantly increased fracture risk in the stratum of 30-59 days of GC prescription. In addition, female patients who received GC (≥ 1 and < 2.5 mg PSL/day) for 90 days in the initial 90 days of GC therapy had a significantly increased fracture risk. CONCLUSIONS: GC exposure in the initial 90 days of GC therapy was dose-dependently associated with hip and clinical vertebral fracture risk. GC may increase fracture risk with lower doses for shorter durations than previously reported. Fracture risk assessment three months after glucocorticoid (GC) therapy initiation is recommended. We found that GC exposure in the initial 90 days of GC therapy at lower daily doses for shorter durations than previously reported were significantly and dose-dependently associated with fracture risk using a nationwide health insurance claims database.

Impact of preexisting interstitial lung disease on mortality in COVID-19 patients from the early pandemic to the delta variant epidemic: a nationwide population-based study.

BACKGROUND: COVID-19 patients with preexisting interstitial lung disease (ILD) were reported to have a high mortality rate; however, this was based on data from the early stages of the pandemic. It is uncertain how their mortality rates have changed with the emergence of new variants of concern as well as the development of COVID-19 vaccines and treatments. It is also unclear whether having ILD still poses a risk factor for mortality. As COVID-19 continues to be a major concern, further research on COVID-19 patients with preexisting ILD is necessary. METHODS: We extracted data on COVID-19 patients between January 2020-August 2021 from a Japanese nationwide insurance claims database and divided them into those with and without preexisting ILD. We investigated all-cause mortality of COVID-19 patients with preexisting ILD in wild-type-, alpha-, and delta-predominant waves, to determine whether preexisting ILD was associated with increased mortality. RESULTS: Of the 937,758 adult COVID-19 patients, 7,333 (0.8%) had preexisting ILD. The proportion of all COVID-19 patients who had preexisting ILD in the wild-type-, alpha-, and delta-predominant waves was 1.2%, 0.8%, and 0.3%, respectively, and their 60-day mortality was 16.0%, 14.6%, and 7.5%, respectively. The 60-day mortality significantly decreased from the alpha-predominant to delta-predominant waves (difference - 7.1%, 95% confidence intervals (CI) - 9.3% to - 4.9%). In multivariable analysis, preexisting ILD was independently associated with increased mortality in all waves with the wild-type-predominant, odds ratio (OR) 2.10, 95% CI 1.91-2.30, the alpha-predominant wave, OR 2.14, 95% CI 1.84-2.50, and the delta-predominant wave, OR 2.10, 95%CI 1.66-2.66. CONCLUSIONS: All-cause mortality rates for COVID-19 patients with preexisting ILD decreased from the wild-type- to the more recent delta-predominant waves. However, these patients were consistently at higher mortality risk than those without preexisting ILD. We emphasize that careful attention should be given to patients with preexisting ILD despite the change in the COVID-19 environment.

Evaluating the timing of triple therapy initiation for the treatment of asthma in Japan: prompt versus delayed.

OBJECTIVE: In Japan, the optimal initiation timing and efficacy of single-inhaler triple therapy (SITT) in asthma management remain unexplored. This study investigated SITT initiation timing following an asthma exacerbation, and examined patient demographics and clinical characteristics. METHODS: Observational, retrospective cohort study in patients with asthma aged ≥15 years who initiated SITT following their earliest observed asthma exacerbation (February-November 2021), using data from Japanese health insurance claims databases (JMDC and Medical Data Vision [MDV]). The study period ended May 2022 for JMDC and September 2022 for MDV. Descriptive analyses were performed independently by database. Variables evaluated included timing of SITT initiation post exacerbation (prompt, delayed and late, ≤30, 31-180 and >180 days post index, respectively), patient demographics, clinical characteristics, and pre-index treatment. RESULTS: Of patients in the JMDC and MDV databases, most initiated SITT promptly after an asthma exacerbation, 60.8% (n = 951/1565) and 44.4% (n = 241/543), respectively. Delayed initiation occurred in 22.6% (n = 354/1565) and 26.3% (n = 143/543) of patients, and late initiation occurred in 16.6% (n = 260/1565) and 29.3% (n = 159/543), respectively. Most patients were indexed on a moderate asthma-related exacerbation, 97.1% (n = 1519/1565) and 68.7% (n = 373/543), respectively. CONCLUSION: Most patients with asthma initiated SITT promptly following a moderate exacerbation, with delayed and late initiation more common among patients with complex clinical profiles. The findings underscore the necessity for future research to examine the interaction between patient characteristics, clinical outcomes, and the timing of SITT initiation to optimize treatment strategies, as clinical practice may vary by exacerbation severity.

Evaluation of Medication Adherence Among Prevalent Users in Hypertension, Dyslipidemia, and Diabetes Using Health Insurance Claims: A Population-Based Cohort Study in Japan.

PURPOSE: Hypertension (HT), dyslipidemia (DL), and diabetes mellitus (DM) are major risk factors for cardiovascular diseases. Despite the wide availability of medications to reduce this risk, poor adherence to medications remains an issue. The aim of this study is to evaluate medication adherence of prevalent users in these disease medications (HT, DL, DM) using claims data. Factors associated with non-adherence were also examined. METHODS: Of 7538 participants of the Tsuruoka Metabolomics Cohort Study, 3693 (HT: 2702, DL: 2112, DM: 661) were identified as prevalent users of these disease medications. Information on lifestyle was collected through a questionnaire. Adherence was assessed by a proportion of days covered (PDC) and participants with PDC ≥0.8 were defined as adherent. Predictors of non-adherence were determined by performing multivariable logistic regression. RESULTS: Medication adherence differed by treatment status. Among those without comorbidities, those with HT-only showed the highest adherence (90.2%), followed by those with DM-only (81.2%) and those with DL-only (80.8%). Factors associated with non-adherence in each medication group were skipping breakfast and poor understanding of medications among those with HT medications, females, having comorbidities, having a history of heart disease, and drinking habit among those with DL medications, and good sleep quality and skipping breakfast among those with DM medications. CONCLUSION: While participants showed high medication adherence, differences were observed across medication groups. The identified predictors of non-adherence could help target those in need of adherence support.

Regional Variation in End-of-Life Care just before Death among the oldest old in Japan : A descriptive study.

BACKGROUND: The use of life-sustaining treatment (LST) in the final stage of life is a major policy concern due to increased costs, while its intensity does not correlate with quality. Previous reports have shown declining trends in LST use in Japan. However, regional practice variations remain unclear. This study aims to describe regional variations in LST use before death among the oldest old in Japan. METHODS: A descriptive study was conducted among patients aged 85 or older who passed away between April 2013 and March 2014. The study utilized health insurance claims from Japan's National Database (NDB) to examine the use of cardiopulmonary resuscitation (CPR), mechanical ventilation (MV), and admission to the acute care ward (ACW) in the last 7 days of life. RESULTS: Among 224,391 patients, the proportion of patients receiving LST varied by region. CPR ranged from 8.6% (Chubu) to 12.9% (Shikoku), MV ranged from 7.1% (Chubu) to 12.3% (Shikoku), and admission to ACW ranged from 4.5% (Chubu) to 10.1% (Kyushu-Okinawa). The adjusted odds ratios (AOR) for regional variation compared with Kanto were as follows: CPR (in Shikoku, 1.85 [95% CI 1.73 - 1.98]), MV (in Shikoku, 1.75 [1.63 - 1.87]), and ACW admission (in Kyushu-Okinawa, 1.69 [1.52 - 1.88]). CONCLUSION: The study presents descriptive information regarding regional differences in the utilization of LST for the oldest old. Further research is necessary to identify the factors that contribute to these variations and to address the challenge of improving the quality of end-of-life care.

Type 2 diabetes in the employed population: do rates and trends differ among nine occupational sectors? An analysis using German health insurance claims data.

BACKGROUND: Socioeconomic inequalities in type 2 diabetes (T2D) are well established in the literature. However, within the background of changing work contexts associated with digitalization and its effect on lifestyle and sedentary behavior, little is known on T2D prevalence and trends among different occupational groups. This study aims to examine occupational sector differences in T2D prevalence and trends thereof between 2012 and 2019. METHODS: The study was done on 1.683.644 employed individuals using data from the German statutory health insurance provider in Lower Saxony, the "Allgemeine Ortskrankenkasse Niedersachsen" (AOKN). Predicted probabilities for T2D prevalence in four two-year periods between 2012 and 2019 were estimated based on logistic regression analyses for nine occupational sectors. Prevalence ratios were calculated to illustrate the effect of time period on the prevalence of T2D among the nine occupational sectors. Analyses were stratified by gender and two age groups. RESULTS: Results showed differences among occupational sectors in the predicted probabilities for T2D. The occupational sectors "Transport, logistics, protection and security" and "Health sector, social work, teaching & education" had the highest predicted probabilities, while those working in the sector "Agriculture" had by far the lowest predicted probabilities for T2D. Over all, there appeared to be a rising trend in T2D prevalence among younger employed individuals, with gender differences among occupational sectors. CONCLUSION: The study displayed different vulnerability levels among occupational sectors with respect to T2D prevalence overall and for its rising trend among the younger age group. Specific occupations within the vulnerable sectors need to be focused upon in further research to define specific target groups to which T2D prevention interventions should be tailored.

Trends in inpatient orthopedic surgery during the COVID-19 pandemic in Japan: a nationwide data study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has resulted in substantial morbidity and mortality globally. The National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) covers 99.9% of health insurance claim receipts by general practitioners. The purpose of this study is to investigate the nationwide number of inpatient orthopedic surgeries in Japan during the effect of state of emergency (SoE) due to COVID-19. METHOD: The NDB has been publicly available since 2014. We retrospectively reviewed the NDB from April 2019 to March 2022. We gathered the monthly number of all inpatient orthopedic surgeries. We also classified orthopedic surgeries into the following 11 categories by using K-codes, Japanese original surgery classification: fracture, arthroplasty, spine, arthroscopy, hardware removal, hand, infection/amputation, ligament/tendon, tumor, joint, and others. By using the average number from April to December 2019 as the reference period, we investigated the increase or decrease orthopedic surgeries during the pandemic period. RESULTS: The NDB showed that the average number of total inpatient orthopedic surgeries during the reference period was 115,343 per month. In May 2020, monthly inpatient orthopedic surgeries decreased by 29.6% to 81,169 surgeries, accounting for 70.3% of the reference period. The second SoE in 2021 saw no change, while the third and fourth SoEs showed slight decreases compared to the reference period. Hardware removal and tumor surgeries in May 2020 decreased to 45.3% and 45.5%, respectively, while fracture surgeries had relatively small decreases. CONCLUSION: According to NDB, approximately 1.3 million orthopedic inpatient surgeries were performed or claimed in a year in Japan. In May 2020, the first SoE period of the COVID-19 pandemic, the number of inpatient orthopedic surgeries in Japan decreased by 30%. Meanwhile, the decrease was relatively small during the SoE periods in 2021.

Annual numbers of diagnoses and medical expenses for obstetric diseases in Japan: A report from the National Database of Health Insurance Claims.

AIM: The present study aimed to estimate the total numbers of obstetric diseases diagnosed, total amounts of medical expenses claimed for obstetric diseases, their averages per livebirth, and yearly trends in Japan. METHODS: This is a secondary analysis of the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) (data from 2015 to 2019). The target population was women of reproductive age (15-49 years old) with diseases in pregnancy, childbirth, and the puerperium, defined by having O codes according to the International Classification of Diseases 10th Revision. We calculated the numbers of obstetric diseases diagnosed, amounts of medical expenses claimed for obstetric diseases marked with the "main injury/disease decision flag," and the totals divided by the annual numbers of livebirths, by year and women's age group. RESULTS: From 2015 to 2019, both the numbers of obstetric diseases diagnosed and amounts of medical expenses claimed for obstetric diseases per livebirth were on an upward trend, whereas the total numbers of obstetric diseases diagnosed were decreased. Women in advanced age groups had a higher number of diagnoses and a higher amount of medical expenses for obstetric diseases per livebirth. "Preterm labour without delivery" had the highest amounts of medical expenses claimed for and the second highest numbers of diagnoses throughout the study period. CONCLUSIONS: This study suggests that pregnant women in Japan would have an increasing number of obstetric complications and necessary medical expenses year by year. Further study is warranted to elucidate these trends and identify possible mitigation measures.

[Healthier at work for longer? Trends in life years free of cardiovascular and musculoskeletal diseases in the employed and general population based on health insurance claims data]. / Länger gesund im Beruf? Trends in den Lebensjahren frei von Herz-Kreislauf- und Muskel-Skelett-Erkrankungen in GKV-Daten für die Erwerbstätigen- und Allgemeinbevölkerung.

BACKGROUND: Our study focuses on the development of disease-free life years of two disease groups with high public health relevance: musculoskeletal diseases (MSD) and cardiovascular diseases (CVD). Against the backdrop of prolonged working lives, the development of disease-free life years in the working-age population is compared with the trend in the employed population. Differences between occupational groups are also examined. METHODS: The study is based on data from the statutory health insurance provider AOK Lower Saxony (N = 2,001,225). Incident cases were identified based on the diagnosis data. The expected years free of MSD and CVD were calculated using multistate life table analysis for three periods between 2006 and 2018. The occupational group is identified via the occupational key. Three groups are distinguished: unskilled and semi-skilled workers, skilled workers and specialists, and highly skilled workers. RESULTS: Life years free of MSD clearly decreased in the general population and among the employed population. The decrease was strongest in the higher-skilled occupational groups. Life years free of CVD increased in the general population. The increase was weaker among the employed population. The only occupational group showing increases were men in unskilled and semi-skilled occupations. DISCUSSION: The study shows that disease-free life years among employed persons developed in some cases worse than in the general population. For the analysed disease groups MSD and CVD, there are clear inequalities between occupational groups, which decreased somewhat over time. The inequalities and the decrease in years free of MSD highlight the high public health relevance and the need for effective prevention strategies to prevent CVD and MSD in working age.

Cholesterol and breast cancer risk: a cohort study using health insurance claims and health checkup databases.

PURPOSE: This study aimed to investigate the association between serum cholesterol and triglyceride levels and breast cancer risk in Japanese women. METHODS: We retrospectively evaluated the association between the levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs) and the incidence of breast cancer in a cohort study by using the health insurance claims and health checkup data from a database provided by JMDC Inc. We included 956,390 women who were insured between April 2008 and June 2019, identified breast cancer cases by using validated definitions, and estimated the risk of breast cancer by using multivariable Cox proportional hazards regression models adjusted for potential confounders. RESULTS: During the 2,832,277 person-years observation period (median 2.4 years), 6284 participants were diagnosed with breast cancer. There was marginally significant association between LDL-C and breast cancer risk when comparing the highest and lowest quintiles and at the clinical cutoff values for diagnosing hyperlipidemia. HDL-C was not associated with breast cancer. However, when stratified by age groups (< 50 and ≥ 50), HDL-C was inversely associated with breast cancer risk in women over 50 years old. TG was not associated with breast cancer risk. CONCLUSION: In this population, there was a modest association of LDL-C at the clinical cutoff values for diagnosing hyperlipidemia (140 mg/mL), and there were no associations of HDL-C and TG with breast cancer risk.

Hip and vertebral fracture risk after initiating antidiabetic drugs in Japanese elderly: a nationwide study.

INTRODUCTION: We aimed to clarify the risks of initiating antidiabetic drugs for fractures using a nationwide health insurance claims database (NDBJ). MATERIALS AND METHODS: Patients aged ≥ 65 years initiating antidiabetic drugs at the outpatient department were enrolled after a 180-day period without prescribed antidiabetic drugs and followed with during 2012-2018 using NDBJ. The adjusted hazard risks (HRs) of each antidiabetic drug (thiazolidine, alpha-glucosidase inhibitor, dipeptidyl peptidase-4 [DPP-4] inhibitor, sulfonylurea, glinide, and insulin) for fractures compared with biguanide were obtained adjusting for age, gender, polypharmacy, dementia, and the other antidiabetic drugs. RESULTS: The DPP-4 inhibitor was the most often prescribed antidiabetic drug followed by biguanide with prescribed proportions of 71.7% and 12.9%. A total of 4,304 hip fractures and 9,388 vertebral fractures were identified among the 966,700 outpatient participants. Compared with biguanide, insulin, alpha-glucosidase inhibitor, and DPP-4 inhibitor were related to increased hip fracture risks. Vertebral fracture risk was higher in outpatients prescribed with insulin, thiazolidine, and DPP-4 inhibitor compared with biguanide. Patients prescribed insulin for hip and vertebral fractures' adjusted HRs were 2.17 (95% CI 1.77-2.66) and 1.45 (95% CI 1.24-1.70), respectively. Those prescribed DPP-4 inhibitor for hip and vertebral fractures' adjusted HRs were 1.27 (95% CI 1.15-1.40) and 1.20 (95% CI 1.12-1.28), respectively. CONCLUSIONS: Initiating insulin increased the risk of not only hip fractures but also vertebral fractures. Patients initiating antidiabetic drugs had increased risks of hip and vertebral fractures compared with those initiating biguanide independently for age, gender, polypharmacy, and dementia in the Japanese elderly.

Association between pharmacotherapy and secondary hip fracture in a real-world setting: a nationwide database study.

INTRODUCTION: This study aimed to assess the association between pharmacotherapy and secondary hip fracture incidence. MATERIALS AND METHODS: The correlation between secondary hip fracture incidence and the presence, type, and medication possession ratio (MPR) of pharmacotherapy was investigated using medical insurance data acquired from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. RESULTS: Data collected from female patients (n = 1,435,347) were analyzed. The 2-year secondary hip fracture incidence was 3.48% (n = 49,921). Secondary hip fracture was significantly more common in patients without medications (3.80%) than in those with medications (3.00%). Patients receiving selective estrogen receptor modulators (SERMs) had the lowest average age. The crude incidence of secondary hip fracture was the lowest in patients receiving SERMs (n = 2088 [2.52%]), followed by those taking bisphosphonates (n = 11,355 [2.88%]), denosumab (n = 1118 [2.90%]), no medications (n = 32,747 [3.80%]), and parathyroid hormone (PTH: n = 2163 [4.55%]), whereas the age-adjusted incidence was the lowest in patients administered denosumab (2.27%), followed by those taking bisphosphonates (2.47%), SERMs (2.55%), PTH (3.67%), and no medications (3.80%). The mean MPR was the highest in patients taking denosumab (64.9%), followed by those receiving bisphosphonates (58.7%), SERMs (58.2%), and PTH (40.6%) in the no hip fracture group. CONCLUSION: Secondary hip fractures were less likely to occur with medication versus no medication. Differences in the crude incidence of secondary hip fracture based on medications usage might be attributed to background characteristics.

[Methotrexate treatment before use of biologics in rheumatoid arthritis : Analysis of guideline compliance]. / Methotrexat-Versorgung vor dem Einsatz von Biologika bei rheumatoider Arthritis : Eine Analyse der Leitliniengerechtigkeit.

BACKGROUND: With the introduction of biologics the treatment landscape for patients with rheumatoid arthritis (RA) has rapidly expanded; however, according to German and European treatment guidelines the use of biologic disease-modifying antirheumatic drugs (bDMARD) is only indicated after insufficient response under methotrexate (MTX) doses of at least 20 mg/week (first-line treatment). The aim of the study was to analyze the guideline compliance of MTX prescription in the outpatient sector prior to treatment with biologics. MATERIAL AND METHODS: Claims data from the AOK Lower Saxony from 2013 to 2016 were provided for all insured patients with a diagnosis of RA and bDMARD prescription during the study period. Within a patient-specific observational period of 180 days prior to the first bDMARD prescription, the maximum prescribed MTX dosage was examined. RESULTS: Data from 90 incident and 315 prevalent RA patients were analyzed. A maximum MTX prescription of < 20 mg/week was observed in 60.0% of incident patients and in 67.0% of prevalent patients. Men had a higher mean MTX maximum dose (17.1 ± 4.8 mg) than women (14.9 ± 5.0 mg; p < 0.0001). Of the study population 29.6% received oral only prescriptions during the observational period. In 12.4% of patients a switch to parenteral administration was made. DISCUSSION: Targeted use of the full spectrum of therapies provided prior to initiation of bDMARD treatment may contribute to cost-effective RA care. This study showed indications for potential deficits in outpatient MTX prescription practice and can raise awareness for efficient treatment.

Longitudinal changes in the prevalence of adult asthma: An epidemiological survey among Japanese salaried employees and their dependents using healthcare insurance claim from 1999 to 2019.

BACKGROUND: Information on changes in asthma prevalence and the treatment status for asthma is used as basic information for taking medical and administrative measures against asthma. However, this information among adults is relatively limited. METHODS: To elucidate changes in the prevalence of asthma and treatment status over time among Japanese adults, health insurance claim data from some health insurance societies covering salaried employees and their dependents were studied longitudinally. Claim data from FY1999 to 2007 were obtained from two health insurance societies, and data from FY 2011 to 2019 were obtained from three different health insurance societies, and changes in standardized asthma prevalence among subjects aged 20-59 years, proportion of asthma patients prescribed ICS, leukotriene receptor antagonist (LTRA), and LABA, and the mean number of acute asthma exacerbations per year were analyzed. RESULTS: The prevalence of asthma increased from 1.6% in 1999 to 3.0% in 2007 and 2.9% in 2011 to 4.6% in 2019. Increased trends in asthma prevalence from 2011 to 2019 were more noticeable in subjects in their 50s than those in their 20s for both sexes. The number of emergency visits related to asthma was 1.5 per year in 1999, which decreased to 0.8 per year in 2019. The proportion of people prescribed all anti-asthma medications (ICS, LTRA, and LABA) increased over time. CONCLUSIONS: The prevalence of adult asthma among Japanese salaried employees and their dependents has increased over the last 20 years, suggesting more attention should be paid to the prevention of this disease in adults.

Comorbidities and co-medications among 28 089 people living with HIV: A nationwide cohort study from 2009 to 2019 in Japan.

OBJECTIVES: Comorbidities are associated with a high burden of disease in people living with HIV (PLWH). The objective was to investigate the prevalence of chronic comorbidities and use of co-medications in PLWH in Japan. METHODS: This study retrospectively analysed clinical information from PLWH receiving antiretroviral therapy (ART) between April 2009 and March 2019. Demographic characteristics, numbers and types of chronic comorbidities, and numbers and types of non-ART co-medications, were described by age groups. The source of data was the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). RESULTS: Overall, 28 089 PLWH (male 91.9%) who used ART were identified. Out of 28 089 PLWH, 81.5% had at least one chronic comorbidity. The numbers of AIDS-defining cancers and non-AIDS-defining cancers in this Japanese cohort were 2432 (8.7%) and 2485 (8.8%), respectively. The cumulative burden of comorbidities including non-AIDS-defining cancer increased with age. Changes in trend between 2009 and 2019 were observed, including a higher proportion of PLWH diagnosed at ≥ 70 years old [2019 (4.7%) vs. 2009 (2.4%)] and a decreasing percentage of patients with AIDS-defining cancers (down from 6.3% to 4.8% between 2009 and 2019). The most common co-medications during the most recent 3-month period were lipid-regulating/anti-atheroma preparations (11.3%), antacids, antiflatulents and anti-ulcerants (9.6%), and agents acting on the renin-angiotensin system (8.1%). The three most common therapeutic categories of co-medications during the study period were antacids, antiflatulents and anti-ulcerants (35.0%), systemic antihistamines (33.7%) and psycholeptics (27.1%). More than 30% of PLWH aged > 40 years used at least one co-medication in a 3-month period, while more than half of PLWH aged > 30 years had at least one co-medication prescribed concomitantly for a total of ≥ 90 days during the study period, and the numbers of co-medications used were greater in the older age groups. CONCLUSIONS: The burden of chronic comorbidities and co-medication were found to be greater in older, as compared to younger patients, among 28 089 PLWH in a nationwide study in Japan. This finding suggests the need to identify elderly PLWH and to appropriately manage their HIV and comorbidities.

Guideline adherence by physicians for management of glucocorticoid-induced osteoporosis in Japan: a nationwide health insurance claims database study.

Risk of fracture due to glucocorticoid-induced osteoporosis (GIO) can be reduced by anti-osteoporosis (OP) medications. The proportion of patients on long-term glucocorticoid therapy who received anti-OP medications according to the GIO management guidelines has increased in recent years, but is still suboptimal. INTRODUCTION: Adherence of physicians to guidelines for glucocorticoid (GC)-induced osteoporosis (GIO) management is currently unclear. This study aimed to clarify the state of guideline adherence by physicians in Japan and identify factors associated with guideline adherence using a nationwide health insurance claims database (NDBJ). METHODS: Patients aged ≥ 50 years who were prescribed GC for ≥ 90 days after 180 days without a GC prescription and who were followed up for osteoporosis (OP) management for the subsequent 360 days during the period spanning 2012-2018 were selected from the NDBJ. Guideline adherence was evaluated with the proportion of patients who received OP management as recommended by the Japanese guidelines. Information on previous vertebral and hip fractures, dementia, and polypharmacy was obtained. Factors associated with OP management were evaluated by logistic regression analysis. RESULTS: A total of 512,296 patients were considered to be at high risk of fracture according to the guidelines. Proportions of patients receiving OP management (BMD testing or anti-OP medications) have increased in recent years. In 2017, 33.7% of men and 55.3% of women received OP management in the initial 90 days of GC therapy. Female sex, previous anti-OP medications, polypharmacy, and higher GC dose were significantly associated with receiving OP management, while dementia showed an inverse association. A prior history of hip fracture, a strong risk factor for future fracture, was not significantly associated with receiving OP management. CONCLUSIONS: Although guideline adherence by physicians has increased in recent years, it remains suboptimal. Further efforts to improve guideline adherence are necessary. TRIAL REGISTRATION NUMBER: The present study is not registered.

The intended purpose and regional patterns of use of antibiotics for managing Clostridioides (Clostridium) difficile infections: An analysis of the National Database of Health Insurance Claims and Specific Health Checkups data of Japan.

INTRODUCTION: We previously showed the trend of antimicrobial use (AMU) for Clostridioides (Clostridium) difficile infection (CDI) using sales data. However, the details of the prescribing medical institutions and regional characteristics are unknown. Therefore, the purpose of this study was to clarify the details of the medical institutions where antibiotics for CDI were prescribed, and evaluate the AMU for CDI and the regional characteristics. METHODS: Antibiotics for CDI, including oral vancomycin (VCM), oral metronidazole (MNZ), and intravenous (IV) MNZ, were collected from the National Database of Health Insurance Claims and Specific Health Checkups (NDB) between 2013 and 2016. The PID (patients/1000 inhabitants/day) was used as an evaluation index for AMU. The PID was calculated using the claim types: inpatient, outpatient, dental, and pharmacy. The PID of each prefecture was calculated for inpatient claims in 2016. RESULTS: The AMU of oral VCM and IV MNZ were observed mainly in the inpatient claims. For oral MNZ, the total AMU in the outpatient and pharmacy claims accounted for approximately 80% per year throughout the study period. For inpatient claims of each prefecture in 2016, the PID of the antibiotics used for CDIs was approximately 3.5 times the difference between the highest and lowest prefectures. CONCLUSIONS: The AMU for CDI that takes into account the purpose of use was clarified by using the information of the prescribed medical institutions that were included in the NDB. Oral MNZ was used frequently in outpatients, and attention should be paid to the acquisition of resistance.

Delayed diagnosis of human immunodeficiency virus infection in people diagnosed with syphilis: A nationwide cohort study from 2011 to 2018 in Japan.

Early treatment of HIV infection depends on timely diagnosis, but many persons living with HIV/AIDS (PLWHA) are unaware of their infection. Though many patients seeking medical attention for sexually transmitted diseases have HIV, many patients' HIV co-infection is undiagnosed in Japan. This is the first report to analyze the timing of syphilis infection in PLWHA of all ages through the use of the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), containing clinical data of the largest group of HIV-positive patients available in Japan. Overall, 1521 PLWHA (male 93.2%) newly diagnosed and started on antiretroviral therapy were identified in 2016, and 646 (42.5%) patients had a diagnosis of syphilis between 2011 and 2018. Although 100 patients were diagnosed with syphilis before their HIV diagnosis, only 17 (17.0%) had been tested for HIV. Over 50 patients per year became infected with syphilis even after their HIV diagnosis (2017, n = 65 (4.3%); 2018, n = 58 (3.8%)). Although early diagnosis of HIV infection is important, most syphilis patients in Japan had not been properly tested for HIV infection. Since a certain number of HIV patients developed syphilis after HIV diagnosis, education for newly diagnosed HIV patients is important.

Syphilis in people living with HIV does not account for the syphilis resurgence in Japan.

OBJECTIVES: This study aimed to determine whether the current syphilis resurgence in Japan is attributable to incident syphilis in people living with HIV (PLWH). METHODS: This observational, retrospective, population-based study used data from the Japanese National Database. Data were extracted for PLWH who received antiretroviral treatment between January 2009 and December 2018. Using these data, along with the annual number of PLWH and syphilis diagnoses in the total population of Japan acquired from the National Institute of Infectious Diseases, the fraction of PLWH with syphilis compared to the total number of syphilis patients reported each year was calculated. RESULTS: There was a dramatic increase in syphilis cases during the study period. However, the incidence of syphilis in PLWH was stable during 2010-2018; the fraction of PLWH with newly diagnosed syphilis remaining at approximately 2% of the total PLWH cases in Japan each year. The proportion of newly diagnosed syphilis cases in PLWH decreased during the study period and accounted for <10% of the total syphilis cases in Japan since 2016 (14.9% in 2015 to 9.5% in 2016 and 5.9% in 2018). An increasing trend in the number of newly diagnosed syphilis cases in PLWH aged >50 years was observed (7.4% in 2010 to 10.4% in 2014 and 14.9% in 2018). CONCLUSIONS: The recent dramatic increase in syphilis cases in Japan was not seen in PLWH. Thus, the resurgence of syphilis in Japan cannot be attributed to its transmission in the PLWH population.

Large-scale health insurance study showed that antibiotic use in infancy was associated with an increase in atopic dermatitis.

AIM: This retrospective large-scale study examined the association between prescribing antibiotics for infants and subsequent atopic dermatitis (AD). METHODS: The data covered the period from 1 January 2005 to 31 December 2014 and were extracted from a Japanese health insurance claims database. The exposure was being prescribed antibiotics at less than 12 months of age and the outcome was a subsequent diagnosis of AD. The primary analysis method was multivariable Cox proportional hazard regression analysis. A sibling-matched analysis was also performed to adjust for shared familial and environmental confounders. RESULTS: This study comprised 85 954 infants: 8654 (10.1%) who had received antibiotics and 77 300 who had not. AD was diagnosed in 1183 (13.7%) and 10 325 (13.4%) infants respectively. The exposed group was more likely to develop AD than the non-exposed group, but this association disappeared when we carried out the secondary, sibling-matched analysis of the two groups. Other risk factors for AD were macrolides, aminoglycosides, food allergies and histamine H1 receptor antagonists. CONCLUSION: Antibiotic use in infancy was associated with a subsequent increase in the incidence of AD. This association should be considered when prescribing antibiotics, but antibiotic use may not be a critical factor for the development of AD.