Changes in surgery rates among hospitalized patients with inflammatory bowel disease in Japan from 2015 to 2019: A nationwide administrative database analysis.

BACKGROUND AND AIM: Treatment of inflammatory bowel disease (IBD), consisting of ulcerative colitis (UC) and Crohn's disease (CD), has advanced with the application of biologics or Janus kinase inhibitor (JAKi); however, some patients still need surgery. We assessed time trends of surgery and biologics or JAKi variety in Japan. METHODS: Patients hospitalized due to IBD were analyzed using Diagnosis Procedure Combination data between 2015 and 2019. Longitudinal trend analysis was performed for demographics, and interrupted time-series analysis was performed to examine the association between surgery rates and an increase in the types of biologics or JAKi. RESULTS: Totally, 37 867 cases with UC and 35 493 cases with CD were analyzed. Over 5 years, the surgery rate decreased in both UC and CD. The proportion of biologics and JAKi usage increased in UC and stabilized in CD. Between decreasing surgery and expanding treatment options of biologic or JAKi, interrupted time-series analysis results showed no significant correlation (level change in UC, -1.13, 95% confidence interval [CI]: -2.11 to -0.16, P = 0.0235; slope change in UC, -0.05, 95% CI: -0.26 to 0.16, P = 0.6372; level change in CD, -0.55, 95% CI: -1.82 to 0.71, P = 0.3815; slope change in CD, -0.22, 95% CI: -0.63 to 0.19, P = 0.2892). CONCLUSIONS: In Japan, from 2015 to 2019, the use of biologics or JAKi increased for UC and slightly decreased for CD, while the number of surgeries decreased in both. Our findings suggest that more widespread use of biologics or JAKi therapy could reduce surgeries in patients with IBD.

Inventory of real-world data sources in Japan: Annual survey conducted by the Japanese Society for Pharmacoepidemiology Task Force.

PURPOSE: The Database Task Force of the Japan Society for Pharmacoepidemiology began its annual surveys of databases available for clinico and pharmacoepidemiological studies in 2010. In this report, we summarize the characteristics of the databases available in Japan based on the results of our 2021 survey to illustrate the recent developments in the infrastructure for database research in Japan. METHODS: We included 20 major databases from the academia, government, or industry that were accessible to third parties. We used a web-based questionnaire to ask the database providers about their characteristics, such as their organization, data source(s), numbers of individuals enrolled, age distribution, code(s) used, and average follow-up periods. RESULTS: We received responses from all 20 databases approached: eight hospital-based databases, six insurer-based databases, four pharmacy-based databases, and two in the "other" category. Among them, 17 contained information from medical claims, pharmacy claims, and/or Diagnosis Procedure Combination data. Most insurer databases contained health check-up data that could be attached to the claims component. Some hospital-based databases had data from electronic medical records. Most insurer-based databases collected data from the insurers of working-age employees and therefore had limited coverage of older people. Most databases coded their medication data using the Japanese reimbursement codes, and many provided Anatomical Therapeutic Chemical Classification codes. CONCLUSIONS: The number of databases available for clinico and pharmacoepidemiological research and the proportion of the population they cover are increasing in Japan. The differences in their characteristics mean that the appropriate database must be selected for a particular study purpose.

Differences in asthma-related outcomes by anti-IL-5 biologics, omalizumab, and dupilumab based on blood eosinophil counts.

BACKGROUND: Selecting optimal biologics based on type 2 biomarkers has been of interest in severe asthma treatment. However, few direct biomarker stratification-based comparisons have been made. OBJECTIVE: To compare the effectiveness of anti-IL-5 (mepolizumab, benralizumab), omalizumab, and dupilumab in reducing the number of hospitalizations from asthma and exacerbations across all and eosinophil-stratified subgroups. METHODS: A retrospective cohort study using the National Hospital Organization database (2016-2020) was performed. Asthmatic patients using biologics were selected, and the baseline backgrounds of the groups were balanced using inverse probability treatment weighting for propensity scores. Weighted rate ratios (RRs) were obtained using a Poisson regression model. RESULTS: Among the 320 patients with asthma using biologics, 205 (64.1%), 75 (23.4%), and 40 (12.5%) were categorized into the anti-IL-5, omalizumab, and dupilumab groups, respectively. After weighting, there were 47.1, 30.0, and 62.6 hospitalizations per 100 person-years [omalizumab vs. anti-IL-5: weighted RR, 0.61 (0.34-1.08); dupilumab vs. anti-IL-5: 1.48 (0.81-2.72)], and 117.0, 134.6, and 287.3 exacerbations per 100 person-years [omalizumab vs. anti-IL-5: 1.13 (0.83-1.54); dupilumab vs. anti-IL-5: 2.69 (1.91-3.78)] in these respective groups. In patients with eosinophil of ≥ 300/µL, the dupilumab group had more exacerbations compared with the anti-IL-5 group [weighted RR, 2.85 (1.82-4.46)]. In patients with eosinophil of < 300/µL, the omalizumab group had fewer hospitalizations compared with the anti-IL-5 group [weighted RR, 0.32 (0.13-0.51)]. CONCLUSION: Anti-IL-5 biologics may be more effective than dupilumab in patients with high blood eosinophil counts, while less effective than omalizumab in patients with low eosinophil counts.

Effect of prednisolone and saireito co-administration on T-cells of rheumatoid arthritis patients.

OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune disease. Methotrexate (MTX) and prednisolone (PSL) are used in combination for severe RA therapy. However, it can increase the risk of osteoporosis and osteonecrosis. Saireito (114) can be used to reduce PSL dose owing to its immunosuppressive effects. However, the effect of combination therapy of PSL+114 on the immune system of RA patients remains unknown. This study compared the effect of PSL alone and PSL+114 on peripheral blood mononuclear cell (PBMC) proliferation, T-cell subsets, and cytokine production in adult RA patients receiving MTX monotherapy. METHODS: We isolated PBMCs from 14 consenting RA patients, and cultured them with PSL (0.0001-1.0 µM) in combination with or without 114 (300 µg/mL) for 96 h in the presence of concanavalin A. We measured the proliferation rates of PBMC, proportions of CD4+, CD8+, and CD4+CD25+Foxp3+T-cells (induced T-regulatory cells), and concentrations of interferon-γ, interleukin (IL)-6, IL-10, IL-17A, and tumour necrosis factor in the culture supernatant. RESULTS: Compared to the blank, the PBMC proliferation rate significantly decreased at a reduced PSL concentration after 114 administration. The 50% inhibition concentration was 0.43 µM PSL for the PSL-only group as compared to 0.29 µM PSL for the PSL+114 co-administration group. The PSL+114 co-administration group had a significantly higher concentration of IL-6 compared to the PSL-only group. CONCLUSIONS: The use of 114 in combination with low-concentration PSL intensified its immunosuppressive effect. However, the concentration of IL-6 was elevated in the co-administration group, suggesting exacerbation of RA activity.

Prescription Trends for the Antidiabetic Agents Used to Treat Type 2 Diabetes Mellitus in Japan from 2012-2020: a Time-Series Analysis.

In April 2014, sodium-glucose cotransporter 2 inhibitor (SGLT-2i) was introduced in Japan. In May 2015, the prescription limitation for SGLT-2i was lifted. Subsequently, SGLT-2i was shown to reduce cardiovascular events in patients with type 2 diabetes mellitus (T2DM). SGLT-2i prescription is expected to increase and consequently affect the prescription trends for other antidiabetic agents. Therefore, we evaluated the trends for antidiabetic agent prescriptions in Japan from April 2012 to March 2020. In this study, a dynamic cohort consisting of patients with T2DM derived from the Japan Medical Data Center health insurance database and with at least one antidiabetic agent prescription was investigated. The prescription rates were calculated monthly (/1000 person-months) for each class of antidiabetic agent. The eligible cohort comprised 34333 patients. The prescription rate for dipeptidyl peptidase-4 inhibitor increased from 424.0 in April 2012 to 656.3 in May 2015, and slightly decreased to 635.4 in March 2020. The prescription rate for biguanide consistently increased from 347.2 in April 2012 to 500.1 in March 2020. The prescription rate for sulfonylurea consistently decreased from 393.8 in April 2012 to 172.5 in March 2020. The prescription rate for SGLT-2i consistently increased from 4.1 in April 2014 to 363.1 in March 2020. SGLT-2i prescription increased and may affect the prescription trends for dipeptidyl peptidase-4 inhibitor and sulfonylurea after May 2015, when the prescription limitation for SGLT-2i was lifted. Biguanide prescriptions increased regardless of the introduction of SGLT-2i. The treatment of T2DM in Japan is clearly changing, with a focus on SGLT-2i and biguanide.

Association between volume of patients undergoing stroke rehabilitation at acute care hospitals and improvement in activities of daily living.

BACKGROUND: This study aimed to determine the relationship between the annual volume of patients undergoing rehabilitation per hospital and the outcomes of patients admitted for acute stroke. METHODS: This observational study used nationwide administrative data. Data on stroke patients aged ≥ 20 years who underwent rehabilitation were extracted from 1,182 acute care hospitals in Japan. The exclusion criteria were extended hospital stay exceeding 180 days and death during hospitalization. Hospital volumes were divided into four quartiles of total patients per hospital. The primary outcome was an improvement in activities of daily living from admission to discharge measured using the Barthel index. Poisson regression analysis of activities of daily living improvement was performed using inverse probability of treatment weighting. RESULTS: High rehabilitation volume was significantly correlated with improvements in activities of daily living using the "very low group" as a reference (risk ratio [95% confidence interval]): 1.06 [1.05-1.08], P<0.001). Low volume was also significantly associated with activities of daily living improvement (risk ratio [95% confidence interval]: 1.04 [1.03-1.06], P<0.001). CONCLUSIONS: The annual volume of stroke patients undergoing multidisciplinary rehabilitation at a specific hospital may be a factor in the degree of patient improvement in activities of daily living.

Economic and clinical burden from carbapenem-resistant bacterial infections and factors contributing: a retrospective study using electronic medical records in Japan.

BACKGROUND: Antimicrobial resistance is a major threat to global health and the world economy. The economic burden of carbapenem-resistant infections has not previously been evaluated. We aimed to compare the potential economic burden and clinical outcomes between carbapenem-resistant infections and carbapenem-susceptible infections in Japan. METHODS: We conducted a retrospective cohort study using electronic medical records. Patients aged 15 years or older and with the diagnosis of pneumonia, urinary tract infection, biliary infection, and sepsis were included. Multivariable regression models with random effects were used to estimate the impact of carbapenem resistance on cost, length of hospital stay, and in-hospital mortality. RESULTS: Among the 9,517 patients, 86 (0.9%) had carbapenem-resistant (CR) infections. Compared to carbapenem-susceptible (CS) infections, the patients with the CR infections were significantly more likely to receive mechanical ventilation (37.2 vs. 21.2%, P-value = 0.003), antibiotics (88.4 vs. 63.0%, P-value < 0.001), and especially carbapenem (31.4 vs. 8.3%, P-value < 0.001), before the bacterial culture test positive. Significantly higher median costs were found for the CR infections than the CS infections in the categories of medications (3477 US dollars vs. 1609 US dollars), laboratory tests (2498 US dollars, vs. 1845 US dollars), and hospital stay (14,307 US dollars vs. 10,560 US dollars). In the multivariable regression analysis, the length of stay was 42.1% longer and the cost was 50.4% higher in the CR infections than in the CS infections. The risk of in-hospital mortality did not differ between the two groups (odds ratio 1.24, 95% CI 0.72-2.11), due to the small sample size. The result was robust with a similar trend in the analysis using the inverse probability treatment weighting method. CONCLUSIONS: Compared to carbapenem-susceptible infections, carbapenem-resistant infections were associated with a higher cost and a longer length of stay. Detailed cost analysis showed significant differences in the categories of medication, laboratory tests, and hospital stay. To our knowledge, this study is the first to assess the potential economic burden of carbapenem-resistant infections using a large hospital-based database.

Association between pre-admission anticoagulation and in-hospital death, venous thromboembolism, and major bleeding among hospitalized COVID-19 patients in Japan.

PURPOSE: The coagulation activation leads to thrombotic complications such as venous thromboembolism (VTE) in patients with coronavirus disease-2019 (COVID-19). Prophylactic anticoagulation therapy has been recommended for hospitalized COVID-19 patients in clinical guidelines. This retrospective cohort study aimed to examine the association between pre-admission anticoagulation treatment and three outcomes: in-hospital death, VTE, and major bleeding among hospitalized COVID-19 patients in Japan. METHODS: Using a large-scale claims database built by the Medical Data Vision Co. in Japan, we identified patients hospitalized for COVID-19 who had outpatient prescription data at least once within 3 months before being hospitalized. Exposure was set as pre-admission anticoagulation treatment (direct oral anticoagulant or vitamin K antagonist), and outcomes were in-hospital death, VTE, and major bleeding. We conducted multivariable logistic regression analyses, adjusting for a single summarized score (a propensity score of receiving pre-admission anticoagulation) for VTE and major bleeding, due to the small number of outcomes. RESULTS: Among the 2612 analytic patients, 179 (6.9%) had pre-admission anticoagulation. Crude incidence proportions were 13.4% versus 8.5% for in-hospital death, 0.56% versus 0.58% for VTE, and 2.2% versus 1.1% for major bleeding among patients with and without pre-admission anticoagulation, respectively. Adjusted odds ratios (95% confidence intervals) were 1.25 (0.75-2.08) for in-hospital death, 0.21 (0.02-1.97) for VTE, and 2.63 (0.80-8.65) for major bleeding. Several sensitivity analyses did not change the results. CONCLUSIONS: We found no evidence that pre-admission anticoagulation treatment was associated with in-hospital death. However, a larger sample size may be needed to conclude its effect on VTE and major bleeding.

Impact of breakthrough trials on prescription trends of sodium-glucose cotransporter-2 inhibitors in Japan: An interrupted time-series analysis.

WHAT IS KNOWN AND OBJECTIVE: Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) have been increasingly prescribed for the treatment of type 2 diabetes mellitus (T2DM). We aimed to investigate the impact of clinical trials presenting remarkable results on the prescription of SGLT-2is and the relationship between the impact and generalisability of the breakthrough trials on SGLT-2is. METHODS: This retrospective cohort study involved 32,949 patients with T2DM who were prescribed at least one antidiabetic agent in the Japan Medical Data Center health insurance database. Prescription rates of SGLT-2is were calculated monthly from April 2014 to March 2020. We evaluated the impact of the EMPA-REG OUTCOME study for an Asian subgroup on the prescription rate of empagliflozin and the impact of the CANVAS/CANVAS-R study on the prescription rate of canagliflozin. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated using the quasi-Poisson regression model in the overall population, subgroup with a history of cardiovascular disease (high-risk group), and subgroup without a history and risk factors of cardiovascular disease (low-risk group). RESULTS AND DISCUSSION: The EMPA-REG OUTCOME study for the Asian subgroup led to increased prescription rates of empagliflozin 3 months after its publication in the overall population and high-risk group but not in low-risk group (IRR [95% CI]: 1.40 [1.17-1.66], 1.39 [1.05-1.84], and 1.00 [0.79-1.27], respectively). The increase in high-risk group may be appropriate because this study included patients with a history of cardiovascular disease only. The CANVAS/CANVAS-R study led to increased prescription rates of canagliflozin 3 months after its publication in the overall population, high-risk group, and low-risk group (IRR [95% CI]: 1.52 [1.06-2.19], 1.39 [1.06-1.83], and 1.81 [1.20-2.75], respectively). The increase in low-risk group may not be appropriate because this study did not include patients without a history or risk factors of cardiovascular disease. WHAT IS NEW AND CONCLUSION: The breakthrough trials increased prescription rates not only for patients to whom the trial results could be extrapolated but also for those in whom trial benefits were not certain. Our findings suggest that information about breakthrough trials may need to be provided along with data on trial result generalisability.

[Analysis the Selection of Opioid Analgesics with Mild and Moderate Cancer Pain Patients for Opioid Naïve].

In 2018, the World Health Organization revised its cancer pain therapy, abolishing the three-step pain relief ladder and recommending the use of opioid analgesics(OA)according to the pain intensity. Of opioid naive patients who were admitted to Chibaken Saiseikai Narashino Hospital from July 2015 to June 2017, treatment with weak OA was initiated in 13 patients(WOA group)and low-dose strong OA in 12 patients(SOA group). The numerical rating scale values immediately before the start of OA and 3, 7 and 14 days later were not significantly different between the 2 groups. As for adverse events, the frequency of occurrence(p=0.01)and the prolongation of the last onset date(p=0.02)were significant in the WOA group for constipation. When the factors related to OA selection were analyzed using logistic regression analysis, there was no significance. We reported the analysis results regarding OA selection in OA naive patients.

Prognosis of patients with liver cirrhosis: A multi-center retrospective observational study.

AIM: Despite advances in the management of liver diseases and changes in the etiology of cirrhosis, few studies have updated the prognosis of cirrhosis. This study aimed to clarify the recent prognosis of cirrhosis and identify risk factors for death. METHODS: In this retrospective observational study by the Hepatic Disease Network of the National Hospital Organization in Japan, chart reviews were performed to follow patients with cirrhosis beginning in 2011. We conducted Kaplan-Meier survival time analyses stratified by Child-Pugh classification and albumin-bilirubin grade. Cox regression analysis was used to identify risk factors for death. RESULTS: We identified 444 eligible patients from 25 hospitals, including 303 (68%), 110 (25%), and 31 (7%) patients with Child-Pugh classes A, B, and C, respectively. Hepatitis C virus infection was the cause of cirrhosis for 63% of the patients. The 1-year and 5-year cumulative survival rates of patients with Child-Pugh classes A, B, and C were 90% and 61%, 78% and 42%, and 65% and 25%, respectively. The 1-year and 5-year cumulative survival rates of patients with albumin-bilirubin grades 1, 2, and 3 were 98% and 80%, 91% and 56%, and 58% and 23%, respectively. Cirrhosis classification (Child-Pugh and albumin-bilirubin), age, liver cancer, and untreated esophageal varices were associated with increased hazard of death. CONCLUSIONS: Little improvement was observed in the prognosis of cirrhosis compared with previous reports, and the prognosis of Child-Pugh class C cirrhosis remained poor. Untreated esophageal varices were identified as a risk factor for death.

Healthcare utilization associated with adherence to antibiotics for abdominal surgeries in Japan: cross-sectional analysis of administrative database.

BACKGROUND: Since patients receiving surgery may experience surgical site infections, therapeutic guidelines for reducing hospitalization time and cost include appropriate antibiotic use. However, the association between adherence to therapeutic guidelines and healthcare utilization is currently unclear. OBJECTIVES: This study aimed to confirm the positive association between the adherence to guidelines of antibiotic therapy and a reduction in the length of stay and cost of hospitalization, especially considering the high infection rates in abdominal surgery. METHODS: This cross-sectional study used administrative data (diagnosis procedure combination data) collected using the case-mix system implemented in acute-care hospitals in Japan. We assessed the length of hospital stay and cost of hospitalization for patients who received prophylactic antibiotic for abdominal surgeries consistent with therapeutic guidelines. The data of patients aged 15 years or older who received appendectomy, laparoscopic cholecystectomy or inguinal hernia repair were extracted. The appropriateness of antibiotic prophylaxis was evaluated in terms of the Japanese guidelines for antibiotic selection and treatment duration. To assess the mean difference in antibiotic costs and length of stay, we performed the propensity score matching by confounding factors. Furthermore, we assessed the progress in healthcare utilization of this therapy over a decade. RESULTS: Of the 302 233 patients who received single general surgery from April 2014 to March 2016, 198 885 were eligible for analysis after applying the exclusion criteria (143 975 in the adherence and 54 910 in the non-adherence group). Each group comprised 48 439 patients after propensity score matching. Inappropriate antibiotic selection and duration were observed in 9294 (9.8%) and 687 (0.7%) of inguinal hernia repairs, 6431 (25.3%) and 311 (1.2%) of appendectomies and 38 134 (48.5%) and 391 (0.5%) of laparoscopic cholecystectomy cases, respectively. After propensity score matching by operation type, average hospitalization length (6.5 [SD 3.8] and 7.3 [SD 4.8] days) and costs (536 000 [SD 167 000] JPY and 573 000 [SD 213 000] JPY) differed significantly between adherence and non-adherence groups. CONCLUSION: The results revealed that unnecessary healthcare utilization was associated with failure to adhere to therapeutic guidelines for prophylactic antibiotic therapy in elective general surgeries. We concluded that the progress of reduction in length of hospitalization over the decade was successful. Notably, adherence to treatment duration was better than that was 10 years ago. In this decade, administrators in hospitals have attempted to reduce the duration of hospitalization by developing various clinical pathways for surgical procedures and quality indicators. However, 15 877 patients (8.7%) were prescribed oral antibiotics the day after surgery. These observations should be evaluated further.

Validity of administrative database detection of previously resolved hepatitis B virus in Japan.

The risk of hepatitis B virus (HBV) reactivation has increased owing to advances in the immunosuppressive therapy field. However, the HBV reactivation incidence among patients with previously resolved HBV (prHBV) infection during immunosuppressive therapy for rheumatoid arthritis (RA) remains unclear. The objective of this work is to describe the validity of detecting prHBV infection from administrative data through comparisons with chart abstraction and determine the incidence of HBV reactivation during immunosuppressive therapy for RA in Japan. In this retrospective cohort study, data on selected patients were extracted from administrative claims data. To identify patients with prHBV infection and de novo hepatitis, and HBsAg carriers, we conducted chart abstraction. The incidence rate of de novo hepatitis was 1.23 of 100 person-years. The positive predictive value (PPV) and its 95% confidence interval (CI) of administrative data for the identification of suspected prHBV infections was 85.8% (95% CI: 81.7%-89.3%). This study evaluated the PPV of the algorithm of HBV-DNA testing with immunosuppressive therapy performed four times or more per year for the detection of prHBV infection from administrative data. Additionally, we determined the incidence rate of HBV reactivation among preHBV infections during immunosuppressive therapy for RA to be 1.23 of 100 person-years.

Factors associated with 30-day readmission of patients with heart failure from a Japanese administrative database.

BACKGROUND: Numerous studies have been conducted in many countries to identify the factors associated with readmission of patients with heart failure (HF). However, there have been no such studies utilizing a large-scale administrative database in Japan. This study aimed to establish the factors associated with 30-day readmission of patients with HF using a Japanese nationwide administrative database. METHODS: Data of the index admissions of 68,257 patients discharged from 1057 participating hospitals between April 1, 2012 and March 31, 2013 were analyzed. Patients were divided into the 30-day readmission group and no readmission group according to whether unplanned HF readmission occurred within 30 days after discharge. Study variables included age, sex, New York Heart Association functional class (NYHA) at admission, Charlson Comorbidity Index (CCI), length of stay in hospital (LOS), body mass index (BMI) at admission, hospital volume reflected by the number of cases hospitalized with HF, and medical treatment at discharge. RESULTS: The 30-day readmission and no readmission groups included 4479 and 63,778 patients, respectively. The independent factors associated with the increase in 30-day readmission were older age, higher NYHA, higher CCI, and use of the following drugs at discharge: beta blockers, loop diuretics, thiazide, and nitrates. In contrast, the independent factors associated with the decrease in 30-day readmission were longer LOS, higher BMI, and the use of angiotensin converting enzyme inhibitors (ACEs) or angiotensin II receptor blockers (ARBs), calcium channel blockers, and spironolactone. CONCLUSIONS: The results suggest that, especially during the first few weeks after discharge, careful management of HF outpatients with advanced age, high disease severity, multiple comorbidities, or taking beta blockers, loop diuretics, thiazide, and nitrates at discharge may be crucial for reducing the 30-day readmission rate.

Association of Antipsychotic Drugs with the Risk of Recurrent Venous Thromboembolism: A Retrospective Study of Data from a Japanese Inpatient Database.

BACKGROUND: Approximately a decade has passed since the addition of venous thromboembolism to the list of significant adverse reactions of antipsychotic drugs. However, only a few studies have investigated the relationship between antipsychotic use and venous thromboembolism in the Japanese population. PURPOSE: We aimed to evaluate the risk of recurrent venous thromboembolism in users of antipsychotic drugs and update the evidence on venous thromboembolism in the Japanese population. METHODS: A cross-sectional retrospective analysis of data from a large Japanese claims database, managed by Medical Data Vision Co. Ltd., was conducted. Adult patients who experienced venous thromboembolism between October 2014 and September 2018 in acute care hospitals were identified. The risk of recurrent venous thromboembolism was evaluated with logistic regression using demographic variables. The data of patients using antipsychotic drugs within specific therapeutic classes were also evaluated. RESULTS: We included 8960 patients (mean age, 69 years; 59.2% female). Recurrent venous thromboembolism was observed in 686 patients (7.7%). The risk of recurrent venous thromboembolism was significantly higher in younger patients [< 65 years: reference; 65-74 years: odds ratio (OR) 0.81, 95% confidence interval (CI) 0.66-0.99, p = 0.04; ≥ 75 years: OR 0.77, 95% CI 0.64-0.94, p = 0.01], those with history of surgery (OR 1.39, 95% CI 1.18-1.65, p = 0.01), and anticoagulant users (OR 2.25, 95% CI 1.46-3.48, p = 0.01) and was significantly lower in the presence of comorbidities (OR 0.68, 95% CI 0.58-0.81, p< 0.01) and fractures (OR 0.49, 95% CI 0.26-0.94, p = 0.03). Long-term antipsychotic drug prescriptions (> 14 days) were associated with a higher risk of venous thromboembolism than short-term prescriptions (≤ 14 days) (OR 1.56, 95% CI 1.04-2.34, p = 0.03). CONCLUSIONS: In patients with a history of venous thromboembolism, particular attention should be paid to recurrence in younger patients. If antipsychotic drugs are prescribed for > 14 days to patients with a history of venous thromboembolism, they should be administered carefully, guided by reported findings. Further evaluations using different databases or populations are required to generalize the findings of this study.

Age-related differences in the effectiveness of rehabilitation to improve activities of daily living in patients with stroke: A cross-sectional study.

Background: This study aimed to reveal differences in the effectiveness of rehabilitation in improving activities of daily living (ADL) in patients with acute stroke across age groups and propose age-appropriate rehabilitation strategies. Methods: This observational study analyzed nationwide administrative data of inpatients admitted to hospitals with acute stroke between April 1, 2018, and March 31, 2020. The data included the average length of daily rehabilitation sessions, weekly frequency of rehabilitation sessions, and initiation of rehabilitation within three days. The primary outcome was the improvement in the Barthel Index (BI) score from admission to discharge. We classified the patients based on age and analyzed improvements in ADL according to rehabilitation characteristics. Results: An increased daily rehabilitation dose was associated with improved ADL, except in patients aged <65 years (risk ratios and 95% confidence intervals [CIs] in the 65-74, 75-85, and ≥85 age groups: 1.20 [1.14‒1.27], 1.21 [1.15‒1.27], and 1.43 [1.34‒1.53], respectively; all p <0.001 vs. <65 years: 1.05 [0.98-‒1.12]; p=0.18). A rehabilitation frequency of seven sessions per week was associated with improved ADL in the 75-85-year and ≥85-year age groups (1.06 [1.02‒1.10] and 1.08 [1.03‒1.13], respectively; both p <0.001). The effects of initiating rehabilitation within three days on ADL post-admission did not differ across age groups. Conclusions: Increasing the daily dose of rehabilitation was significantly associated with improved ADL in all age groups while increasing the frequency of rehabilitation per week improved ADL in older and very old patients.

Association between Cognitive Impairment Severity and Polypharmacy in Older Patients with Atrial Fibrillation: A Retrospective Study Using Inpatient Data from a Specialised Geriatric Hospital.

This study aimed to investigate the association between cognitive impairment and polypharmacy in patients with atrial fibrillation prone to cognitive decline, and to elucidate if the Dementia Assessment Sheet for Community-based Integrated Care System 21-Items (DASC-21) severity classification indicates drug adjustment. This retrospective cohort study used the DASC-21 and Diagnosis Procedure Combination data at a specialised geriatric hospital with patients hospitalised between April 2019 and March 2022. The association between cognitive severity evaluated using the DASC-21 and polypharmacy was investigated using a multivariate logistic regression model. Data of 1191 inpatients (44.3% aged ≥85 years, 49.0% male) were analysed. Compared with severe cognitive impairment, mild (odds ratio [OR]: 3.33, 95% confidence interval [CI]: 1.29-8.57) and moderate (OR: 2.46, 95% CI: 1.06-5.72) impairments were associated with concurrent use of ≥6 medications. Antithrombotics were related to polypharmacy. The ORs did not change with 6, 8, or 10 medications (2.11 [95% CI: 1.51-2.95, p < 0.001], 2.42 [95% CI: 1.79-3.27, p < 0.001], and 2.01 [95% CI: 1.46-2.77, p < 0.001], respectively). DASC-21 severity was associated with polypharmacy in patients with atrial fibrillation, with a trend toward decreased polypharmacy from moderate to severe. The DASC-21 may serve as an indicator for drug adjustment in clinical practice.

Epidemiology of progressive multifocal leukoencephalopathy in Japan and effectiveness of mefloquine: A retrospective analysis of a nationwide inpatient database.

INTRODUCTION: Progressive multifocal leukoencephalopathy (PML) is an infrequent yet devastating neurological infection that arises in immunocompromised patients. The epidemiological features of PML in Japan and its evolution in recent years remain unclear. There are no established treatments that directly target PML. Although mefloquine has shown in vitro activity against JC virus, its clinical effectiveness has not been confirmed in population-level studies. METHODS: We retrospectively analyzed the admission data of patients with PML recorded in the Diagnosis Procedure Combination (DPC) database from fiscal year 2010 to 2020 (11 years). Descriptive statistics were used to illustrate the epidemiological features. Changes in the frequency of PML admission, underlying diseases, and in-hospital mortality over time were also examined. Furthermore, we evaluated the effectiveness of mefloquine in improving activities of daily living at discharge using propensity score matching. RESULTS: We identified 610 PML cases diagnosed by the treating physicians, which may include possible PML. Among them, 419 were first-time admissions. The median age at admission was 62.0 years, and 62.8% were men. HIV was the most common underlying condition, accounting for 22.9% of cases, followed by hematologic malignancies (18.4%), and autoimmune diseases (17.9%). Over the study period, the frequency of PML admissions showed an increasing trend, whereas the in-hospital mortality rate showed a decreasing trend. The effectiveness of mefloquine was not confirmed. CONCLUSIONS: The results of this study will help clarify and update the clinical picture of PML in Japan. The DPC database was shown to be useful tool for epidemiological research on rare infectious disease such as PML.

Increasing daily duration of rehabilitation for inpatients with sporadic inclusion body myositis may contribute to improvement in activities of daily living: A nationwide database cohort study.

OBJECTIVE: To analyse the association between the daily duration of rehabilitation for inpatients with sporadic inclusion body myositis and improvement in activities of daily living, using a Japanese nationwide inpatient administrative claims database. METHODS: Data were extracted regarding inpatients with sporadic inclusion body myositis who had undergone rehabilitation between 1 April 2018 and 31 March 2021. The mean daily duration of rehabilitation was categorized into 2 groups: > 1.0 h (longer rehabilitation) and ≤ 1.0 h (shorter rehabilitation). The main outcome was improvement in activities of daily living from admission to discharge, measured using the Barthel Index. For the main analysis, a generalized linear model was used. RESULTS: In total, 424 patients with sporadic inclusion body myositis met the eligibility criteria for inclusion in the study. The main analysis found a significant difference in improvement in activities of daily living between the longer rehabilitation and shorter rehabilitation groups after adjusting for confounders (risk ratio (95% confidence interval), 1.37 (1.06-1.78)). CONCLUSION: A longer daily duration of rehabilitation results in improved activities of daily living for inpatients with sporadic inclusion body myositis.

Bevacizumab-induced proteinuria and its association with antihypertensive drugs: A retrospective cohort study using a Japanese administrative database.

Proteinuria is a major side-effect of the anti-tumor drug bevacizumab, although its incidence and risk factors in the real world are still unclear. Although renin-angiotensin-aldosterone system inhibitors are used clinically to prevent proteinuria, their efficacy remains unclear. The aim of the present study was to reveal the incidence and risk factors of bevacizumab-induced proteinuria and examine the effectiveness of antihypertensive drugs in preventing proteinuria. We conducted a retrospective cohort study using the National Hospital Organization Clinical Data Archives and Medical Information Analysis Databank. Hospitalized patients who received bevacizumab between January 1, 2016, and June 30, 2019, were included. The study outcome was proteinuria within 12 months of bevacizumab administration. Patient characteristics, laboratory tests, and medications were compared between patients with and without proteinuria using multivariable logistic regression analysis. Among the 2,458 patients, 27% developed proteinuria after bevacizumab administration. Nursing dependence (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.89-3.05; P<0.001) and systolic blood pressure ≥140 mmHg (OR, 1.44; 95% CI, 1.17-1.79; P<0.001) were identified as risk factors. Patients with an estimated glomerular filtration rate (eGFR) of 60-89, 45-59, and <45 mL/min/1.73 m2 had 29.7%, 76.8%, and 66.0% higher odds of proteinuria, respectively, than those with an eGFR ≥90 mL/min/1.73 m2. No significant relationship was observed between antihypertensive drugs and the occurrence of proteinuria. More patients may suffer from proteinuria after bevacizumab administration than previously reported. Nursing dependence and systolic blood pressure are predictive risk factors for bevacizumab-induced proteinuria. Patients at risk of proteinuria should be closely monitored.