Fasudil hydrochloride and ozagrel sodium combination therapy for patients with aneurysmal subarachnoid hemorrhage: a cross-sectional study using a nationwide inpatient database.

BACKGROUND: Fasudil and ozagrel are drugs with the same indications for the treatment of cerebral vasospasm in Japan. However, there have been no definitive conclusions on the clinical efficacy of fasudil hydrochloride and ozagrel sodium monotherapy or their combination. Therefore, we aimed to investigate the effectiveness of the combined administration of fasudil hydrochloride and ozagrel sodium in Japanese patients with subarachnoid hemorrhage (SAH). METHODS: This cross-sectional study used Diagnosis Procedure Combination data to assess patients who were hospitalized with SAH and received fasudil hydrochloride or ozagrel sodium between April 2016 and March 2020 (n = 17,346). The participants were divided into three groups based on the treatment received: fasudil hydrochloride monotherapy (F group, n = 10,484), ozagrel sodium monotherapy (O group, n = 465), and fasudil hydrochloride and ozagrel sodium combination therapy (FO group, n = 6,397). The primary outcome was in-hospital mortality. Multivariable adjusted logistic regression analysis (significance level, 5%) was used for data analyses. RESULTS: The results of the multivariable analysis, adjusted for factors considered to impact prognosis, showed that the adjusted odds ratio (OR) with the F group as the reference for in-hospital mortality was 0.94 in the FO group (95% confidence interval [CI]: 0.81-1.08, p = 0.355), with no differences compared to the F group. CONCLUSION: Fasudil hydrochloride and ozagrel sodium had different mechanisms of action, suggesting a synergistic effect of combination therapy. However, a comparison of fasudil hydrochloride monotherapy and combination therapy of fasudil hydrochloride and ozagrel sodium showed no difference in the prognostic effect. Therefore, it was suggested that fasudil hydrochloride monotherapy may be sufficient.

[Analysis of the Effect of Nutritional Status on Pain Treatment in Cancer Patients Using Oral Opioid Analgesics].

In cancer patients, pain control is reportedly affected by the quality of their nutritional status as the disease progresses. We conducted a study of patients who were continuously using oral opioid analgesics for the treatment of cancer pain at Chibaken Saiseikai Narashino Hospital from September 2020 to August 2022. Patient characteristics and pain treatments were compared between the well-nourished group(mGPS 0 or 1, n=20)and poorly nourished group(mGPS 2, n=47). Univariate analysis revealed significant differences between the 2 groups in terms of sex and the presence or absence of concomitant analgesic adjuvant(p<0.05). According to the multivariate analysis, the presence or absence of concomitant analgesic adjuvant was a significant related factor, with an odds ratio of 11.409(95% confidence interval: 2.645-49.217, p=0.001). For patients in the poorly nourished group who were able to maintain a general condition that allowed for oral administration, treatment was continued without affecting pain control. In the well-nourished group, most patients used gabapentinoids as an analgesic adjuvant, whereas in the poorly nourished group, avoidable side effects, such as dizziness and lightheadedness, might affect the patient's quality of life.

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.

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.

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.

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.

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.

Characteristics and in-hospital mortality of patients with COVID-19 from the first to fifth waves of the pandemic in 2020 and 2021 in the Japanese Medical Data Vision database.

Objectives: We aimed to describe patient characteristics, healthcare utilization, and in-hospital mortality among patients with COVID-19 in Japan across waves. Methods: Using a large-scale hospital-based database, we identified patients hospitalized for COVID-19 in the first (January-June 2020), second (June-October 2020), third (October 2020-February 2021), fourth (March-June 2021), and fifth (June-December 2021) waves. We summarized patient characteristics, healthcare utilization, and in-hospital mortality during each wave and performed multivariable logistic regression analyses for in-hospital mortality. Results: From the first to fifth waves, the number of patients (mean age ± standard deviation, years) was 2958 (61.2 ± 22.8), 7981 (55.6 ± 25.3), 18,788 (63.6 ± 22.9), 17,729 (60.6 ± 22.6), and 23,656 (51.2 ± 22.3), respectively. There were 190 (6.4%), 363 (4.5%), 1261 (6.7%), 1081 (6.1%), and 762 (3.2%) in-hospital deaths, respectively. The adjusted odds ratios for in-hospital deaths (95% confidence interval) were 0.78 (0.65-0.95), 0.94 (0.79-1.12), 0.99 (0.84-1.18), 0.77 (0.65-0.92), in the second to fifth waves, respectively, compared with the first wave. Conclusions: In-hospital COVID-19 mortality improved from the first to the second wave; however, during the third and fourth waves, mortality was as serious as in the first wave. Although in-hospital mortality during the fifth wave improved, careful monitoring is needed for upcoming waves, considering changing patient and viral characteristics.

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.

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.

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.

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.

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.

Rehabilitation of Patients With Acute Ischemic Stroke Who Required Assistance Before Hospitalization Contributes to Improvement in Activities of Daily Living: A Nationwide Database Cohort Study.

OBJECTIVE: To assess the effect of early implementation of and longer daily duration of rehabilitation on patients with acute ischemic stroke who require assistance with activities of daily living (ADL) before hospital admission. DESIGN: Nationwide, cohort, observational study from April 2018 to March 2019. SETTING: Acute care hospitals in Japan. PARTICIPANTS: The Japanese national Diagnosis Procedure Combination database was searched for the period between April 2018 and March 2019. Of the 330,672 patients with ischemic strokes identified, 53,523 met the inclusion criteria of being older than 20 years, having a prehospital modified Rankin Scale score of 3, 4, or 5, and having undergone rehabilitation (N=53,523). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Improvement in ADL from admission to discharge using the Barthel Index. The effects of the following 3 rehabilitation variables on ADL improvement were evaluated: (1) average daily duration of rehabilitation; (2) rehabilitation started within 3 days after admission (early rehabilitation); and (3) rehabilitation started 1 day after admission (very early rehabilitation). RESULTS: Early rehabilitation was significantly associated with improvements in ADL (odds ratio, 1.19; 95% confidence interval, 1.10-1.28; P≤.001). A longer duration of rehabilitation was also significantly associated with ADL improvement (≥2.0 hours: odds ratio, 2.49; 95% confidence interval, 2.26-2.75; P≤.001) compared with a ≤1 hour of rehabilitation (1.1-2.0 hours: odds ratio, 1.35; 95% confidence interval, 1.29-1.42; P≤.001). CONCLUSIONS: Early implementation of rehabilitation and a longer duration of rehabilitation per day improved the ADL of patients who required assistance before the onset of cerebral infarction.

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.

Longer Daily Duration of Supervised Rehabilitation after Laparoscopic Surgery for Colorectal Cancer Improves Activities of Daily Living.

OBJECTIVE: To evaluate the effect of a supervised rehabilitation programme with longer hours per day on activities of daily living after laparoscopic surgery for colorectal cancer. DESIGN: This study represents retrospective observational use of nationwide administrative data. PATIENTS: Eligible patients (n = 8,633) were first diagnosed with colorectal cancer between 1 April 2017 and 31 March 2018, underwent laparoscopicassisted colorectal resection, and began rehabilitation within 3 days of surgery. METHODS: Patients underwent a long (40 min or more) or short (less than 40 min) supervised rehabilitation programme, defined as rehabilitation under physiotherapist and occupational therapist supervision. The main outcome measure was improvement in activities of daily living from postoperative day 0 to day 14 using Nursing Need Degree. RESULTS: Patients who underwent longer daily supervised rehabilitation (n = 7,173) showed greater improvements in activities of daily living at 14 days after laparoscopic surgery than patients who underwent shorter daily supervised rehabilitation (n = 1,460) (odds ratio (95% confidence interval; 95% confidence interval): 1.42 (1.22-1.64), p < 0.001). The rate of postoperative complications did not differ between groups. CONCLUSION: Longer daily supervised rehabilitation for colorectal cancer improves activities of daily living after laparoscopic surgery.

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.

Influence of inpatient rehabilitation after crisis in patients with myasthenia gravis: A retrospective cohort study using a nationwide administrative database in Japan.

BACKGROUND: Growing evidence indicates that carefully programmed rehabilitation can improve symptoms in patients with myasthenia gravis (MG). However, evidence on rehabilitation to aid in recovery from a myasthenic crisis is lacking. This study aimed to examine the association between inpatient rehabilitation and recovery in the activities of daily living (ADL) after a myasthenic crisis. METHODS: We retrospectively identified patients hospitalized due to myasthenic crisis in a nationwide administrative database in Japan. Patients were divided into two groups based on the intensity of rehabilitation after weaning from mechanical ventilation. We evaluated the influence of rehabilitation on recovery in the ADL by comparing the two groups in Kaplan-Meier and Cox proportional hazard model analyses. RESULTS: We extracted the data of 437 cases treated from April 1, 2016 to March 31, 2020. High-intensity rehabilitation was associated with delayed recovery in the ADL on Kaplan-Meier analysis (p = 0.024, log-rank test). A similar result was obtained after adjusting for covariates in the Cox proportional hazard model analysis (hazard ratio: 0.69; 95% confidence interval: 0.48-0.99; p = 0.043). CONCLUSIONS: High-intensity rehabilitation performed in current inpatient settings may not contribute to recovery in the ADL after a myasthenic crisis in patients with MG. Despite this study's large sample size, further research is necessary to reach firm conclusions.