Medical Data Vision Research Articles

Risk of non-hypoglycemic agents for hypoglycemia-related hospitalization in patients with type 2 diabetes: a large-scale medical receipt database analysis

IntroductionHypoglycemia is listed as an adverse effect in the package inserts of not only hypoglycemic agents but also many other drugs. We aimed to clarify real-world factors related to an...

Comparison of Nutrition Indices for Prognostic Utility in Patients with Sepsis: A Real-World Observational Study.

Nutritional status of critically ill patients is an important factor affecting complications and mortality. This study aimed to investigate the impact of three nutritional indices, the Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), and Controlling Nutritional Status (CONUT), on mortality in patients with sepsis in Japan. This retrospective observational study used the Medical Data Vision database containing data from 42 acute-care hospitals in Japan. We extracted data on baseline characteristics on admission. GNRI, PNI, and CONUT scores on admission were also calculated. To evaluate the significance of these three nutritional indices on mortality, we used logistic regression to fit restricted cubic spline models and constructed Kaplan-Meier survival curves. We identified 32,159 patients with sepsis according to the inclusion criteria. Of them, 1804 patients were treated in intensive care units, and 3461 patients were non-survivors. When the GNRI dropped below 100, the risk of mortality rose sharply, as did that when the PNI dropped below about 40. An increased CONUT score was associated with increased mortality in an apparent linear manner. In sepsis management, GNRI and PNI values may potentially be helpful in identifying patients with a high risk of death.

Valvular heart disease in Japan: Characteristics and treatment of patients in acute care hospitals in 2019

BackgroundValvular heart disease (VHD) is one of the commonest causes of cardiovascular morbidity and mortality worldwide, with acquired VHD especially prevalent in countries with aging populations. The scope and pattern of disease are not well understood, as some patients are asymptomatic and available options for invasive treatment vary by affected valve. We sought to understand the burden of VHD in Japan including the distribution of patients by valve disease type and age, using administrative claims data from acute care hospitals. MethodsThis was a retrospective descriptive study of patients with VHD diagnosis and at least one record of echocardiography in 2019 documented in the Medical Data Vision database. Affected valve(s) and type of valve disease were characterized using ICD-10 codes; patients undergoing invasive treatment for VHD at the same facility and during the same year as their diagnosis were assessed using procedure codes. ResultsOf 203,398 patients with VHD diagnosis and a record of echocardiography in 2019, 49.0 % had a mitral valve disorder, 44.9 % aortic valve, 22.9 % tricuspid valve, and 2.2 % pulmonic valve (14.9 % of patients had more than one disordered valve). A total of 7201 patients (<4 % of the total diagnosed population) received invasive treatment for VHD in 2019 at the diagnosing hospital. Patients with aortic stenosis (AS) had the highest mean age, at 79 years. Although mitral regurgitation was the most common VHD among diagnosed patients, AS predominated in the cohort of treated patients. A substantial portion of patients undergoing treatment for AS were age 85 years or older (27.2 %). ConclusionsThe cohort of treated patients in 2019 was a small fraction of the total population with a VHD diagnosis in that year. Wide availability of transcatheter treatment for AS in Japan may be allowing more elderly patients to receive intervention than in other types of VHD.

Risk of hospitalized infections in older elderly patients with rheumatoid arthritis treated with tocilizumab or other biological/targeted synthetic disease-modifying antirheumatic drugs: Evaluation of data from a Japanese claims database.

We compared the incidence rates of hospitalized infections (HIs) between tocilizumab (TCZ) and other biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in adults aged ≥75 years with rheumatoid arthritis (RA). We used a Japanese claims database from Medical Data Vision Co., Ltd (Tokyo, Japan) to perform a retrospective longitudinal population-based study in patients with RA who were prescribed b/tsDMARDs between 2014 and 2019. We calculated adjusted risk ratios (aRRs) for HIs in three age groups (<65, ≥65 and <75, and ≥75 years). Of 5506 patients, 2265 (41.1%) were <65 years, 1709 (31.0%) were 65-74 years, and 1532 (27.8%) were ≥75 years. Crude incidence rates (/100 person-years) of HIs were 3.99, 7.27, and 10.77, respectively. In the oldest group, aRRs (95% confidence interval) for HIs (b/tsDMARDs versus TCZ) were as follows: etanercept, 2.40 (1.24-4.61); adalimumab, 1.90 (0.75-4.83); golimumab, 1.21 (0.66-2.23); and abatacept, 0.89 (0.49-1.62). In the other age groups, the noticeable difference was a lower aRR of etanercept versus TCZ in the youngest group (0.30, 0.11-0.85). In patients with RA aged ≥75 years, b/tsDMARDs have a similar risk of HIs to tocilizumab except for etanercept.

Abstract P4-01-26: Real-world treatment duration of subsequent therapy after palbociclib (PAL) in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) in Japan

Abstract Background: PAL is a first-in-class cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) for the treatment of HR+/HER2− ABC. Two CDK4/6is are currently available in Japan; PAL and abemaciclib (ABE). CDK4/6i+endocrine therapy (ET) has shown significant clinical benefits compared to ET alone in clinical trials. CDK4/6i combination therapy is strongly recommended as a first-line (1L) treatment in global and Japanese treatment guidelines. However, no optimal subsequent treatment has been established after discontinuing treatment with CDK4/6i+ET. Substantial data are required to determine whether the available treatment options remain effective after CDK4/6i treatment. Here, we report the treatment pattern of subsequent therapy after PAL in a real-world setting in Japan to provide insights into the optimal subsequent therapy. Methods: This retrospective, observational study utilized a nationwide hospital-based medical claims database managed by Medical Data Vision (MDV). The MDV database, one of the largest medical databases in Japan, covers 26% of acute-care hospitals across Japan, including 226 cancer therapeutic facilities. We evaluated the data of patients who received PAL from September 2017 to June 2021 and subsequently received therapy. Any treatment for ABC initiated within 30 days was considered part of one regimen. The median time-to-treatment failure (TTF) of subsequent therapy was estimated using the Kaplan–Meier method. Results: From the database, we identified 1,170 patients with HR+/HER2− ABC who received PAL, among which 398 (34%) received combination therapy as 1L treatment. The median age at PAL initiation was 64 years (range 53–72), and 13.0% of the patients were pre-/peri-menopausal. Among the 398 patients, 224 (56.3%) received therapy after PAL+ET. Endocrine-based therapy was commonly used as the first subsequent therapy (n=136; 60.7%), including CDK4/6i+ET (n=70; 31.2%), ET alone (n=39; 17.4%), and everolimus+ET (n=27; 12.1%). Among the 81 (36.2%) patients who received chemotherapy as the first subsequent therapy, 27 (12.1%) received bevacizumab+chemotherapy. The median TTF (95% confidence interval [CI]) of the first subsequent therapy was 7.5 months (6.5–8.4), and that of each subsequent regimen is listed in Table 1. The median TTF (95% CI) for patients received CDK4/6i+ET as first subsequent therapy after PAL+ET was the longest among the regimens, 10.9 months (6.5–15.6). Among the 70 patients, 36 changed only CDK4/6i type, 17 changed only ET type, and 12 changed both CDK4/6i and ET types. The median TTF (95% CI) was 20.1 months (6.5– not reached [NR]), 8.7 months (2.9–11.2), and 7.7 months (2.6–NR), respectively. No obvious trend was observed between the TTF of PAL+ET as a 1L treatment and the TTF of subsequent ABE after the PAL+ET treatment. Conclusion: More than half the patients received endocrine-based therapy after PAL+ET as a 1L treatment, and the observed treatment duration was comparable to the results of clinical trials reported to date, even after PAL treatment. ET+targeted therapy and chemotherapy represent acceptable treatment options after PAL+ET. One-third of patients received CDK4/6i+ET after PAL+ET in Japanese clinical practice; however, further investigation is warranted to confirm that this treatment strategy is effective. Table 1. Median TTF of each subsequent therapy after PAL+ET Citation Format: Masataka Sawaki, Yasuaki Muramatsu, Kanae Togo, Hiroji Iwata. Real-world treatment duration of subsequent therapy after palbociclib (PAL) in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) in Japan [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-26.

Proton Pump Inhibitors and Rhabdomyolysis: Analysis of Two Different Cross-Sectional Databases.

It is unclear whether use of a proton pump inhibitors (PPIs) increases the risk of rhabdomyolysis. To clarify whether use of PPIs increases the risk of rhabdomyolysis. This cross-sectional study analyzed data entered into the Medical Data Vision (MDV) database in Japan and into the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). The MDV data were analyzed to evaluate the association between use of PPIs and rhabdomyolysis. Then, the FAERS data were analyzed to evaluate whether the risk of rhabdomyolysis was increased further when a statin or fibrate was used concomitantly with a PPI. In both analyses, histamine-2 receptor antagonist was set as a comparator because it is used to treat gastric disease. In the MDV analysis, Fisher's exact test and multiple logistic regression analysis were performed. In the FAERS analysis, a disproportionality analysis using Fisher's exact test and multiple logistic regression analysis were performed. Multiple logistic regression analysis of both databases showed a significant association between use of PPIs and an increased risk of rhabdomyolysis (odds ratio [OR] = 1.74-1.95, P ≤ 0.01). However, use of a histamine-2 receptor antagonist was not significantly associated with increased risk of rhabdomyolysis. In the sub-analysis of the FAERS data, use of a PPI did not increase the risk of rhabdomyolysis in patients receiving a statin. The data in 2 separate databases consistently suggest that PPIs may increase the risk of rhabdomyolysis. The evidence for this association should be assessed in further drug safety studies.

Risk of a second cancer and infection in patients with indolent B-cell lymphoma exposed to first-line bendamustine plus rituximab: A retrospective analysis of an administrative claims database.

Bendamustine has a potent immunosuppressive effect because it causes T-cell lymphopenia, which might lead to a second primary malignancy (SPM) and would increase the risk of infection. Using the Medical Data Vision administrative claims database, we compared the cumulative incidence of SPM, infections within 6months, and overall survival (OS) among untreated patients with indolent B-cell lymphomas (iBCL) who received rituximab-based chemotherapy between 2009 and 2020. Patients with grade 3b follicular lymphoma or a previous history of malignancy were excluded. Eligible 5234 patients were assigned to three cohorts: rituximab monotherapy (N=780), RCHOP/RCVP/RTHPCOP (doxorubicin replaced with pirarubicin) (N=2298), or bendamustine/rituximab (BR) (N=2156). There were 589 recorded SPMs, of which myelodysplastic syndromes were the most common (1.7%). The cumulative incidence of SPM was significantly higher in patients treated with BR than in those treated with rituximab monotherapy (p<0.01) or RCHOP/RCVP/RTHPCOP (p<0.0001): the 5-year cumulative incidence function was 18.1%, 12.5%, and 12.9%, respectively. In the Fine-Gray subdistribution hazards model, BR showed a significantly higher cumulative incidence of SPM than RCHOP/RCVP/RTHPCOP (subhazard ratio, 1.33; 95% confidence interval [CI], 1.10-1.61). Furthermore, in sensitivity analysis, a nested case-control study using an entire cohort showed consistent results: the SPM odds ratios (95% CI) of first-line bendamustine, bendamustine after first-line, and any-line bendamustine were 1.43 (1.14-1.78), 1.26 (0.96-1.64), and 1.33 (1.09-1.62), respectively. Regarding infections, adjusted odds ratios (95% CI) of BR compared to RCHOP/RCVP/RTHPCOP were as follows: cytomegalovirus infection, 13.7 (4.88-38.4); bacterial pneumonia, 0.63 (0.50-0.78); and pneumocystis pneumonia, 0.24 (0.11-0.53). There was no significant difference in OS between RCHOP/RCVP/RTHPCOP and BR in patients with follicular, mantle cell, marginal zone, or lymphoplasmacytic lymphomas. In conclusion, treatment strategies that consider the risk of SPM and infections after chemotherapy are warranted in patients with iBCL.

Real-world effectiveness and safety of trifluridine/tipiracil plus bevacizumab in metastatic colorectal cancer: A retrospective observational study using an administrative database.

44 Background: Trifluridine/tipiracil (FTD/TPI) and regorafenib (REG) are standard of care for refractory metastatic colorectal cancer (mCRC). Several phase II trials of FTD/TPI plus bevacizumab (BEV) have been conducted, showing promising efficacy with manageable safety, and it is widely used for patients with refractory mCRC in Japan. No result has been reported for large-scale real-world data directly comparing FTD/TPI plus BEV with FTD/TPI or REG monotherapy. Here, we evaluated the efficacy and safety of FTD/TPI plus BEV in real-world clinical practice. Methods: We used a nationwide claims database provided by Medical Data Vision Co., Ltd. (Tokyo, Japan) in Japan. Eligible patients were aged 20 years or older in mCRC who received their first dose of FTD/TPI or REG between May 2014 and January 2021. The primary outcome was overall survival (OS) in a propensity score matching (PSM) population that was performed matching using a 1:1 ratio for FTD/TPI plus BEV and control group (FTD/TPI or REG) by propensity score. To enhance robustness, sensitivity analyses of OS were performed using the inverse probability treatment weighted (IPTW) approach and the analysis in all eligible population. Main secondary outcomes were OS for subgroups, time to treatment discontinuation (TTD), adverse events (assessed in all eligible population), and post-treatment. Results: The eligible population was 2,369 for FTD/TPI plus BEV and 9,318 for control group (FTD/TPI: 6,500 and REG: 2,818). The PSM population was 1,787 for FTD/TPI plus BEV and 1,787 for control group (FTD/TPI: 1,252 and REG: 535). Median OS (mOS) was 17.0 months for FTD/TPI plus BEV and 11.6 months for control group (HR: 0.70; 95% CI: 0.63–0.78; P &lt; 0.001) in PSM population. Similarly, mOS was longer for FTD/TPI plus BEV compared to that for control group in IPTW analyses (HR: 0.68; 95% CI: 0.65–0.71; P &lt; 0.001) and in all eligible population (HR: 0.68; 95% CI: 0.63–0.73; P &lt; 0.001). In all eligible population, mOS were 17.6 months for FTD/TPI plus BEV and 12.6 months for control group (FTD/TPI: 12.9 months and REG: 12.1 months). Median TTD was 101 days for FTD/TPI plus BEV and 56 days for control group in PSM population (Wilcoxon rank-sum test P &lt; 0.001). The incidence of hand-foot syndrome was significantly higher in REG compared with that in FTD/TPI plus BEV (Fisher's Exact test P &lt; 0.001. Leukopenia incidence was significantly higher in FTD/TPI plus BEV than that in REG (Fisher's Exact test P &lt; 0.001. Granulocyte colony-stimulating factor was administered to 20.6%, 16.5%, and 1.1% of patients in FTD/TPI plus BEV, FTD/TPI, and REG, respectively. Conclusions: The real-world data showed that FTD/TPI plus BEV had significantly longer OS and TTD than FTD/TPI or REG in mCRC. Thus, FTD/TPI plus BEV may be a favorable regimen for refractory mCRC in clinical practice.

Clinical impact of suboptimal RAASi therapy following an episode of hyperkalemia

BackgroundHyperkalemia (HK) is a barrier to optimization of renin-angiotensin-aldosterone system inhibitor (RAASi) therapy in heart failure (HF) and chronic kidney disease (CKD). We investigated cardiorenal risk associated with changes in RAASi regimen after an episode of HK in patients with HF and/or CKD.MethodsThis observational study utilized data from hospital records, claims, and health registers from the US (Optum’s de-identified Market Clarity Data) and Japan (Medical Data Vision). Included patients had an index episode of HK between July 2019 and September 2021 (US), or May 2020 and September 2021 (Japan), with prior diagnosis of HF or CKD (stage 3 or 4), and RAASi use. Risk of a cardiorenal composite outcome (HF emergency visit, HF hospitalization, or progression to end-stage kidney disease) was determined in patients who discontinued RAASi, down-titrated their dose by > 25%, or maintained or up-titrated their dose following the HK episode.ResultsA total of 15,488 and 6020 patients were included from the US and Japan, respectively. Prior to the episode of HK, 59% (US) and 27% (Japan) of patients had achieved > 50% target RAASi dose. Following the episode of HK, 33% (US) and 32% (Japan) of patients did not fill a new RAASi prescription. Risk of the cardiorenal outcome at 6 months was higher in patients who discontinued or down-titrated versus maintained or up-titrated RAASi treatment both in the US (17.5, 18.3, and 10.6%; p < 0.001) and in Japan (19.7, 20.0, and 15.1%; p < 0.001).ConclusionHK-related RAASi discontinuation or down-titration was associated with higher risk of cardiorenal events versus maintained or up-titrated RAASi.

Association of white blood cell count after operative vaginal delivery with maternal adverse outcome: A retrospective cohort study.

The white blood cell count is often used to assess the maternal condition after an operative vaginal delivery. However, it remains unknown whether the maternal white blood cell count on the day after delivery is associated with sequential maternal adverse outcomes, especially infectious complications. The aim of this study was to investigate the association between maternal white blood cell count on the day after operative vaginal delivery and sequential maternal adverse events. The study was a retrospective cohort study using the Medical Data Vision claims database containing administrative claims data, discharge abstracts, and laboratory values in Japan. We identified all patients who underwent operative vaginal delivery with data on maternal white blood cell count from December 2011 to November 2020. The main composite outcome was maternal adverse outcomes, comprising additional treatment for maternal injuries, postpartum intravenous antibiotic use, and intensive care unit use during hospitalization. We conducted a restricted cubic spline analysis to investigate the nonlinear association between white blood cell count and the primary outcome. There were 485 eligible patients including 73 patients with occurrence of the primary outcome. The median (interquartile range) white blood cell count on the day after delivery in all eligible women was 15,170 (12,610-18,300)/mL. In the restricted cubic spline analysis, there was no significant association of white blood cell count with the primary outcome. White blood cell count on the day after operative vaginal delivery was not significantly associated with maternal adverse outcomes during hospitalization.

Real-world evidence on disseminated intravascular coagulation from Japan.

Many descriptive epidemiological and comparative studies using big data have been reported recently from outside Japan. Within Japan, diagnosis procedure combination (DPC) data and medical receipt data are being stored in electronic media, and real-world evidence in various fields has started to be reported. We reviewed clinical studies on disseminated intravascular coagulation (DIC) using DPC data obtained from an insurance database with large numbers of cases and a related commercially available dataset including DPC and laboratory data. After DPC was introduced in 2003, 19 studies on DIC using Japanese national DPC data and two studies using the Medical Data Vision database were reported. Epidemiological findings in seven studies showed that the proportion of drugs administered for each underlying disease differed, with antithrombin and recombinant thrombomodulin (rTM) being used more frequently in clinical settings. In 14 comparative studies on anti-DIC agents, antithrombin for severe pneumonia, postoperative intestinal perforation, and severe burn, and rTM for acute cholangitis were associated with improved survival rates. Large-scale observational studies using big data can show results similar to those of randomized control trials if the quality of individual research is high. Real-world data analysis will be increasingly necessary to complement the evidence gap unfilled by randomized control trials.

Real-World Treatment Patterns, Outcomes and Disease Burden of Japanese Patients with High-Risk Myelodysplastic Syndrome: A Claims Database Study

Introduction Inherent complex pathophysiology of myelodysplastic syndrome (MDS) along with its higher occurrences in elderly population often limits available treatment options. In Japan, azacitidine (AZA) is the only first-line (1L) treatment, which is not cytarabine-based, available for patients (pts) with high-risk MDS (HR-MDS) ineligible for hematopoietic stem cell transplantation (HSCT). Prior autoimmune diseases have been associated with susceptibility of MDS. However, durability of AZA treatment and data on MDS-specific comorbidities, especially immune-driven events are currently lacking in Japanese pts. This study aimed to answer clinical questions on AZA real-world treatment outcomes in Japan, the epidemiology of autoimmune diseases in this specific pt cohort, as well as treatment cost. Methods This was a retrospective, longitudinal study utilizing hospital-based administrative claims for MDS patients in the Medical Data Vision (MDV) database in Japan. Data on pt demographics, clinical characteristics, treatments, procedures and hospitalization records were collected. Adult pts with first a confirmed MDS diagnosis either as an inpatient or twice in outpatient setting during the identification period (1October 2008 - 30 September 2017), who had a bone marrow biopsy in ±3 months from index date and at least 1 MDS-related treatment post-index date, were included in this real-world study. Pts with confirmed acute myeloid leukemia (AML) diagnosis or who had any history of HSCT, graft-versus-host-disease or transplant-related disorder/complications were excluded. As IPSS/R scoring is unavailable in MDV, pts were classified as HR-MDS if they had either AZA treatment or HSCT within 6 months post-index date, or pancytopenia diagnosis within 6 months post-index date and initiated AZA within 12 months. Results Of 6204 pts who met the eligibility criteria (main cohort), 2138 pts were assigned as HR-MDS. The median age of pts in the main cohort was 74.0 years (range: 18.0 - 100.0 years, ≥60 years old: 87.8%) vs 73.0 years (range: 20.0 - 95.0 years; ≥60 years old: 88.6%) in the HR-MDS cohort. Mean Charlson Comorbidity Index was 1.7 (± 1.66) and 1.6 (± 1.47) for the main cohort and HR-MDS cohort respectively. The proportion of transfusion-dependent pts in the main cohort was 9.4% vs 7.1% of patients in the HR-MDS cohort. Among 2138 pts with HR-MDS, 251 pts reported having concomitant autoimmune disease with rheumatoid arthritis (32.3%), glomerulonephritis (26.7%) and seronegative arthritis (23.1%) being the most common. More pts in the main cohort (53.2%) compared to pts with HR-MDS (38.9%) received anti-anemic drugs, G-CSF and iron chelators as supportive therapy at 1L. Compared to 39.5% pts in main cohort, 88.3% pts with HR-MDS received antineoplastic agents at 1L therapy. In HR-MDS cohort, 2078 pts received AZA in different cycles (1-3 cycles: 40.5%, 4-6 cycles: 21.1%, 7-9 cycles: 11.5%, >9 cycles: 26.9%) but only 121 pts received intensive chemotherapy (1 cycle: 90.1%, 2 cycles: 9.1%, >2 cycles: 0.8%). Median duration of MDS-specific treatment for patients with HR-MDS was 9.8 months. Significantly higher median OS (P<0.001) was achieved in pts with HR-MDS who received more cycles of AZA (Fig. 1: 1-3 cycles: 14.6 months, 4-6 cycles: 21.4 months, 7-9 cycles: 22.8 months, >9 cycles 40.8 months). After controlling for death as a competing risk, the cumulative incidence function (CIF) of HSCT and AML transformation was not affected by the number of cycles of AZA received. Although more cycles of AZA treatment increased the total treatment cost, median cost per pt per month was inversely affected with the lowest cost for pts receiving >9 cycles (Fig. 2). Conclusion Our findings based on the real-world data analysis in Japanese pts follow the similar trend of elderly pts with HR-MDS mostly receiving AZA as 1L treatment. Despite higher median OS being associated with higher number of AZA cycles, only ~27% pts with HR-MDS received >9 cycles of AZA. Autoimmune disease was reported by 11.7% of pts with HR-MDS. Although treatment cost increased with number of cycles of AZA received, median cost per pt per month was lowest in patients receiving >9 cycles. The cost per pt per month for other MDS-related treatment as well as costs for blood transfusions and infection related treatments were lower as increasing cycles of AZA were given which contributed to lower cost per pt per month. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

ORIHIME II Study: Background, Treatment Status, and Outcomes of Patients with Acquired Hemophilia A with Low Activities of Daily Living Scores or Undergoing Rehabilitation - a Japanese Health Claims Database Analysis

Background: Acquired hemophilia A (AHA) is a rare disease in which autoantibodies (inhibitors) develop against blood coagulation factor (F)VIII, resulting in significantly reduced FVIII activity, with onset of bleeding symptoms such as sudden subcutaneous hemorrhage and muscular hemorrhage. The database-based study, 'Obtain Real-World Insights of Acquired Hemophilia A Patients in Japan' (the ORIHIME study) first reported data on rehabilitation and activities of daily living (ADL) scores for patients with AHA in Japan, which had previously been scarce (Ogawa et al. Blood 2021). The need to clarify the clinical experience of patients undergoing rehabilitation and patients with low ADL scores, who are considered to have relatively poor treatment and prognosis among AHA patients, has become apparent. This study evaluated the association between patient background, medication use, and outcomes among patients with AHA who underwent rehabilitation or had low ADL scores between April 1, 2008, and October 31, 2021. Methods: The study was conducted using the Medical Data Vision Co., Ltd. database. Patients with a diagnosis of AHA who were hospitalized and were administered immunosuppressants following admission were included. The primary endpoint examined the association of actual rehabilitation practices and total ADL score (measured using the Barthel Index) at discharge with patient background, medication use, and clinical outcomes. Total ADL score was calculated by adding together the scores for each of the following activities: eating, transferring (e.g. from bed to chair and back), ambulating, toilet use, bathing, mobility, stairs, dressing, and control of bladder and bowel movement. A score of 85 or higher corresponds with 'independence with minimal assistance' in the Barthel Index, therefore, in this analysis, participants are categorized by scores of <85 and ≥85 (Sulter et al. Stroke 1999). The risk of infection due to immunosuppressive therapy was a secondary endpoint. Results: Overall, 427 patients were included in this study. The mean (standard deviation [SD]) age of the patients was 76.3 (11.3) years, and 264 (61.8%) were male. A total of 249 patients underwent rehabilitation following admission to hospital. The median (range) time to the start of rehabilitation from the date of admission to hospital was 10.0 (1.0-133.0) days, and a high proportion of patients had a period of <2 weeks between admission to hospital and the start of rehabilitation (n=142/249 [57.0%]). Hemostatic agents used during rehabilitation were bypassing agents in 44 cases, FVIII in two cases, and tranexamic acid in 50 cases. Of the patients who received hemostatic agents, 36/44 (81.8%) patients who received bypassing agents, 2/2 (100.0%) patients who received FVIII, and 38/50 (76.0%) patients who received tranexamic acid started rehabilitation <2 weeks after the date of admission (Table 1). The ADL score at discharge was ≥85 points in 192 patients (45.0%) and <85 points in 186 patients (43.6%). Most patients with an ADL score at discharge of ≥85 (n=144/192 [75.0%]) were discharged from the hospital to home (attending outpatient visits at the same hospital), and for patients with ADL scores of <85 at discharge, the highest proportion of patients were transferred to other hospitals (n=92/186 [49.5%]; Table 2). Conclusions: Hemostatic agents may be necessary to start rehabilitation earlier. Post-discharge outcomes may be related to ADL scores at discharge. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Epidemiology and Treatment Patterns of Venous Thromboembolism: an Observational Study of Nationwide Time-Series Trends in Japan.

Previous studies on anticoagulation treatment trends have mostly focused on hospitalized patients. This study aimed to clarify the treatment status of patients with venous thromboembolism (VTE) in Japan from 2011 to 2018, including outpatients, and to assess adherence with current guidelines. Data of inpatients and outpatients who were treated for VTE were extracted from a nationwide claims database (Medical Data Vision Co., Ltd., Tokyo, Japan) and analyzed. The study included 79,330 patients with VTE; half were diagnosed during hospitalization for diseases other than VTE. The proportion of outpatient treatment increased significantly from 2015 to 2018 (Cochran-Armitage trend test, P < 0.0001), while 80% were anticoagulated in hospital after pulmonary embolism (PE) diagnosis. The proportion of patients with VTE treated as outpatients was no lower than the proportion of inpatients, even in the presence of active cancer, and there were no clear differences in anticoagulant choices. Treatment with direct oral anticoagulants (DOACs) did not always include the recommended initial intensification therapy. There was wide variation in the duration of DOAC treatment and the median duration of use was shorter than that recommended in VTE treatment guidelines. While the gradual increase in VTE outpatient treatment appears to be in line with guideline recommendations, PE outpatient treatment could be further facilitated. The large proportion of patients diagnosed with VTE during hospitalization for other conditions suggests the importance of further utilizing in-hospital manuals for thrombosis prevention. The presence or absence of cancer did not appear to affect the basic treatment strategy of anticoagulation for VTE. Future studies are expected to better define the characteristics of patients who can be safely and effectively treated in an outpatient setting, and to examine whether anticoagulation for a shorter treatment period than recommended by the guidelines or DOAC therapy without initial intensification would improve patient outcomes.

Practice patterns and outcomes for triple-class exposed patients with relapsed/refractory multiple myeloma in Japan.

Aim: Treatment options for triple-class exposed (TCE) patients with multiple myeloma (MM) in Japan are limited. Materials & methods: Retrospective observational study using the Medical Data Vision database (April 2008-April 2021). Eligible adults with MM received a new post-TCE treatment. Treatments, healthcare resource utilization (HCRU)and costs (per patient per month [PPPM]) were analyzed with subgroup analyses by prior stem cell transplantation (SCT vs No SCT). Results: Of 459 TCE patients, 216 (47%) had post-TCE treatment of whom 194 (90%) had no prior SCT. Median duration of the first post-TCE line of therapy (LOT) was 2months; 49% of No SCT patients received a subsequent LOT. Total healthcare costs were comparable between No SCT and SCT groups (¥1.3million PPPM each; US$12,328 and $12,391, respectively), driven by treatment costs. Median post-index overall survival(n=216) was 15.8months (95% CI: 10.5, 22.3). Conclusion: New treatments with better effectiveness are needed for patients with TCE MM in Japan.

Treatment pattern and clinical outcomes in portopulmonary hypertension: A database study in Japan.

Portopulmonary hypertension (PoPH) is a complication associated with portal hypertension. Since the epidemiological study in Japan was limited, this study aimed to investigate the characteristics, treatment patterns, and prognosis of PoPH patients in real-world data. The characteristics and treatment patterns of PoPH (n=386) and portal hypertension without pulmonary arterial hypertension (portal hypertension w/o PAH) (n=96 463) were analyzed based on the Medical Data Vision (MDV) dataset from April 2008 to September 2020. Survival-time analyses of emergency hospitalization and mortality were also conducted between matched pair cohorts of PoPH (n=210) and portal hypertension w/o PAH (n=840). Among 386 PoPH patients, the Child-Pugh classification of PoPH group comprised patients with Class A (59 [15.3%]), B (109 [28.2%]), and C (42 [10.9%]), and missing (176 [45.6%]). Regarding the feature of PoPH group, the proportion of primary biliary cholangitis (PBC) (13.7%) and splenomegaly (9.8%) was higher compared with portal hypertension w/o PAH group. The survival time of all-cause hospitalization in PoPH group was shorter than portal hypertension w/o PAH group in matched pair cohort (P < 0.001 by log-rank test). Of PoPH patients, the frequency of PAH-specific medicine usage within 90 days was monotherapy of 79 patients (20.5%), combination therapy of 64 patients (16.6%), and PAH-specific medicine usage of 243 patients (63.0%). This was the first study demonstrating that high proportion of PBC and splenomegaly and a greater risk of hospitalization were observed in PoPH patients based on the analysis using administrative claim database.

Clinical features of Japanese patients with acute hepatic porphyria.

Acute hepatic porphyria (AHP) is a family of rare genetic diseases of heme biosynthesis characterized by severe neurovisceral attacks. The clinical characteristics of patients with AHP as well as the prevalence of AHP in Japan are not well understood. The objectives of this study were to describe clinical characteristics of AHP at time of diagnosis in Japanese patients and to estimate the prevalence of AHP. Patients with porphyria were selected from Japan's Medical Data Vision health care claims database between April 2008 and June 2020. Patient characteristics before and at time of AHP diagnosis were evaluated. Prevalence per 100 000 was estimated during the study period. A total of 391 cases of AHP were included. At time of AHP diagnosis, mean age was 44 years, and the most common type was acute intermittent porphyria. Median time to diagnosis was 3months, but some patients remained undiagnosed for several years. The most common complications included metabolic disorders (54%) and diabetes mellitus (39%). In addition, the well-known complications of AHP, including hypertension (22%) and malignant neoplasms of digestive organs (22%), were observed. About 10% of patients received medications that may have aggravated porphyria attacks. The estimated prevalence of AHP in Japan during the study period was 1.18 cases per 100 000 population. At time of diagnosis, many patients with AHP in Japan are already experiencing a high burden of disease-related complications. Raising AHP awareness may aid physicians in providing an earlier diagnosis and reducing lifetime disease burden.

Estimating the prevalence, clinical characteristics, and treatment patterns of hypertrophic cardiomyopathy in Japan: A nationwide medical claims database study

BackgroundLimited data are available regarding therapies for hypertrophic cardiomyopathy (HCM). This study assessed the prevalence, clinical characteristics, and treatment patterns of HCM in Japan. MethodsThis retrospective database study analyzed data from 438 hospitals in the Japan Medical Data Vision database from 2016 to 2020. We identified 3913 patients (15 %) with obstructive HCM (oHCM) and 21,714 patients (85 %) with nonobstructive HCM (nHCM). ResultsThe estimated total number of patients with oHCM and nHCM in 2020 among Japanese hospitals was 8500 and 43,500, respectively. The prevalence of oHCM and nHCM steadily increased by 27 % and 12 %, respectively, from 2016 to 2020, with a 1:5.2 ratio of oHCM to nHCM in 2020. The mean age of the oHCM and nHCM populations was 72 and 70 years, respectively, and comorbidities included atrial fibrillation (AF) (oHCM, 33.8 %; nHCM, 32.2 %), other arrythmia (30.1 %; 27.6 %), and stroke (16.6 %; 16.4 %). Furthermore, 45.0 % of oHCM and 37.7 % of nHCM patients had undergone at least one hospitalization. A substantial number of HCM patients aged between 20 and 59 years reported AF (oHCM, 17–37 %; nHCM, 4–24 %) and stroke (oHCM, 0–12 %; nHCM, 3–10 %). β-blockers (oHCM, 64.0 %; nHCM, 42.1 %) were the most frequently prescribed treatment, followed by Na channel blockers (29.5 %; 5.7 %), calcium channel blockers (18.1 %; 8.8 %), direct oral anticoagulants (14.5 %; 15.2 %), and warfarin (11.0 %; 11.4 %). ConclusionsThis study provides important information on the current epidemiological and clinical characteristics of HCM in Japan.

Real-world assessment of anti-platelet therapies for recurrent stroke prevention in non-atrial fibrillation Japanese patients after recent ischemic stroke or transient ischemic attack

Abstract Background Stroke is one of the leading causes of cardiovascular-related deaths and disability for adults in Japan and is more commonly seen among the elderly. The risks of developing a secondary stroke resulting in permanent damage after the incident ischemic stroke (IS)/transient ischemic stroke (TIA) are very high. It is critical to understand the treatment landscape for the secondary stroke prevention (SSP) and unmet needs of patients with prior IS/ TIA events. Purpose To evaluate the antiplatelet therapy (APT) treatment patterns for SSP after first hospitalization for IS/TIA events among the Japanese population. Methods Japan's Medical Data Vision (MDV) from Q12011 to Q22021 was used for this study. MDV is a hospital-based claims database covering approximately 35.5 million individuals in the inpatient and outpatient settings among 438 hospitals. Adult patients with an inpatient primary diagnosis of IS/TIA during the index period were identified. Patients require at least one medical claim each quarter within the 1 year before and after index date to ensure longitudinal analysis. Atrial fibrillation patients or patients on oral anticoagulant use were excluded. Patients' characteristics, treatment pattern and duration were evaluated. Results Of 18,948 patients in this study, the mean age was 75 years and 36.7% were female; 91.5% were treated with APT and 8.5% were untreated within 90 days of hospital discharge. Among 17,332 APT treated patients, 76.9% were initiated on single APT (SAPT), 22.7% were initiated on dual APT (DAPT), and &amp;lt;1% were initiated on multiple APT (MAPT). The most used SAPT were aspirin (ASA; 33.2%), clopidogrel (28.7%) or cilostazol (14.8%) and the most used DAPT were ASA+clopidogrel (15.1%), ASA+cilostazol (4.2%) or cilostazol+clopidogrel (2.7%). The median duration of APT was 320, 414 and 411 days for patients who initiated ASA, clopidogrel and cilostazol, respectively. The median duration of APT for patients who initiated ASA+clopidogrel, ASA+cilostazol and cilostazol+clopidogrel was 298, 359 and 473 days respectively. Of patients initiated on ASA+clopidogrel, 52.4% were de-escalated to SAPT (71% clopidogrel, 29% ASA; median duration of 20 days); 36.2% of patients initiated on ASA+cilostazol were de-escalated to SAPT within a median of 19 days (84% cilostazol, 16% ASA); lastly, 54.4% of patients initiated on cilostazol+clopidogrel de-escalated to SAPT within a median of 35 days (76% cilostazol, 24% clopidogrel). Two years after initial hospitalization of IS/TIA, 52%-56% discontinued APT treatments among those previously receiving SAPT while 46%-57% of patients receiving DAPT discontinued treatment. Conclusion Majority of patients at risk of secondary stroke received APT. Further analyses are needed to explore reasons for early APT discontinuation, for no APT use, and to evaluate outcomes of patients in this study. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This study was sponsored by Bristol Myers Squibb and Janssen Research &amp; Development, LLC. – Anonymised and used for statistical purposes only

A Review of Research Studies Using Data from the Administrative Claims Databases in Japan

In Japan, several research studies have used administrative claims databases. However, no study has compared the studies conducted in each database. We assessed the type, design, and research area of each research study using the administrative databases in Japan to illustrate the suitability of the database used for the types of research studies. We reviewed studies from four administrative claims databases (the Japanese National Database of Health Insurance Claims and Specific Health Checkups [NDB]; the DPC Study Group database [DPC]; Japan Medical Data Center [JMDC]; and Medical Data Vision [MDV]). The PubMed database was searched from January 2015 to October 2020. We assessed the type, design, and research area of the abstract or full text of each research study. Overall, 643 studies were included. The number of studies increased from 59 in 2015 to 171 in 2020. Descriptive studies accounted for 62.7% (42 studies) of the studies from the NDB, while the treatment effectiveness studies accounted for 81.7% (211 studies) of the studies from the DPC database and were the most common in the JMDC and MDV. Cohort studies accounted for only 17.9% of the studies on NDB but 45.5% on DPC. The most common research area was medicine, general, and internal medicine (53 studies, 8.4%). The type and design of the studies conducted differed in each database and were influenced by the characteristics of the database used. In the future, it may be necessary to integrate various real-world data databases to increase their comprehensiveness.