Burden of Antimicrobial Resistance in Japan: A Systematic Literature Review and Meta-Analysis.

INTRODUCTION: Antimicrobial resistance (AMR) is one of the most serious public health challenges worldwide, including in Japan. However, there is limited evidence assessing the AMR burden in Japan. Thus, this systematic literature review (SLR) and meta-analysis (MA) were conducted to assess the clinical and economic burden of AMR in Japan. METHODS: Comprehensive literature searches were performed on EMBASE, MEDLINE, the Cochrane Library, and ICHUSHI between 2012 and 2022 following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. MA estimated a pooled effect between the two comparative arms (AMR vs. non-AMR). The results were reported in measures of odds ratios (ORs) for in-hospital mortality and in standardized mean differences (SMDs) for length of stay (LOS) and direct medical costs. RESULTS: Literature searches identified 1256 de-duplicated records, of which 56 observational studies (English, n = 35; Japanese, n = 21) were included. Of note, twenty-two studies (39.3%) compared the AMR group with non-AMR group. In the SLR, in-hospital mortality, LOS, and direct medical costs were higher in the AMR group compared to the non-AMR group. Eight studies were selected for the MA. In the AMR group, the pooled estimate showed a statistically higher in-hospital mortality [random effect (RE)-OR 2.25, 95% CI 1.34-3.79; I2 = 89%; τ2 = 0.2257, p < 0.01], LOS (RE-SMD 0.37, 95% CI - 0.09-0.84; I2 = 99%; τ2 = 0.3600, p < 0.01), and direct medical cost (RE-SMD 0.53, 95% CI 0.43-0.62; I2 = 0.0%; τ2 = 0.0, p = 0.88) versus the non-AMR group. CONCLUSION: Our study presents an overview of the clinical and economic burden of AMR in Japan. Patients with AMR infections experience significantly higher in-hospital mortality, LOS, and direct medical costs compared with patients without AMR infections.

Exploring Current Practice, Knowledge, and Challenges of Sexually Transmitted Infection/HIV Management and Pre-Exposure Prophylaxis Among Japanese Health Care Professionals: A Cross-Sectional Web Survey.

We conducted a web-based survey targeting physicians in specialties of treating sexually transmitted infection (STI) and/or human immunodeficiency virus (HIV) patients to understand the current STI/HIV care practices and their acceptability of and barriers to the prescription of pre-exposure prophylaxis (PrEP) in Japan. A descriptive analysis was used to summarize survey responses. Univariate and multivariable logistic regression were performed to identify factors associated with willingness to prescribe PrEP. Of 316 survey respondents, 57 were specialized in HIV, 90 STI/Urology/Proctology, 55 Obstetrics/Gynecology, and 114 General Practice/Internal Medicine/Dermatology. Proportion of HIV-specialized physicians who interview the patients about risk behaviors tended to be higher than other physician groups (84.2% vs. 54.8%, 47.3%, and 50.9%, respectively), and 53 - 75% of non-HIV-specialized physicians reported that they were incapable of making decisions on HIV medications. Higher PrEP knowledge enhanced the willingness to recommend and prescribe PrEP drugs (odds ratio: 2.31, 95% confidence interval: 1.30-4.10, p = 0.0044), and 45.4% physicians with no PrEP knowledge raised the concern of incapability to respond and manage when an individual is infected with HIV. Educational opportunities on management and prevention measures for both STI and HIV may encourage non-HIV-specialized physicians to be involved in HIV care and to enhance initiation of HIV tests and adoption of PrEP.

Healthcare resource utilization and economic burden of antifungal management in patients with hematologic malignancy in Japan: a retrospective database study.

OBJECTIVE: To examine treatment patterns of real-world antifungal management of patients at high risk of invasive fungal infections (IFI) and evaluate healthcare resource utilization and costs associated with antifungal management of IFIs in Japan. METHODS: This retrospective, observational study extracted data from a hospital-based claims database for patients in Japan who either (a) underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), or (b) were hospitalized with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) and received chemotherapy during the study period of January 2010 to January 2019. RESULTS: 863 patients were included in the allo-HSCT cohort and 4498 patients were included in the AML/MDS cohort. In the allo-HSCT cohort, 91% received more than one antifungal drug during the index hospitalization. In the AML/MDS cohort, approximately 50% received more than one antifungal drug during the index hospitalization. For both the allo-HSCT and AML/MDS cohorts, about 90% of the total cost was attributed to inpatient costs. Of note, both the total cost (the total inpatient and outpatient cost) and the index hospitalization costs were higher in patients treated with multiple antifungal drugs than in those treated with a single antifungal drug during the index hospitalization. Despite being at high IFI risk, 12% of the patients in the AML/MDS cohort did not receive antifungal drugs during the index hospitalization. CONCLUSIONS: Most patients with hematologic malignancy and high IFI risk underwent complicated antifungal management requiring use of multiple drugs, and accounted for high healthcare resource utilization and costs.

Budget impact analysis of Jivi (damoctocog alfa pegol, Bay 94-9027) in severe hemophilia A in Japan.

OBJECTIVE: Hemophilia A (HA) is a genetic bleeding disorder characterized by a deficiency of clotting factor VIII (FVIII) requiring lifelong prophylactic treatment typically with conventional standard half-life recombinant FVIII (rFVIII). Lifelong prophylaxis impacts budget, patient adherence, and long-term outcomes. The consequent economic and treatment burden may be reduced by using novel extended half-life rFVIII. The objective of this analysis was to estimate the budget impact of introducing Jivi (damoctocog alfa pegol, BAY 94-9027), hereafter referred to as BAY 94-9027, as an on-demand and prophylactic treatment for severe HA from a Japanese payer's perspective. METHODS: A global budget impact model was adapted to the Japanese setting using data obtained via a targeted literature review of Japanese sources. The model considered a five-year time horizon for a market without and with BAY 94-9027. Using annual per-patient costs, the total cost of on-demand and prophylactic treatment of adolescent and adult patients with severe HA (without inhibitors) were analyzed. The model used summary of product characteristics (SmPC) and clinical trial dosing, and unit costs from the National Health Insurance (NHI) drug price database. Comparators considered in the model comprised of currently available products in Japan. Projected BAY 94-9027 uptake ranged from 4% to 9% over the five years (2020-2024). RESULTS: Introduction of BAY 94-9027 for the treatment of severe HA is estimated to decrease the overall budget by 1.5%, with a cost saving of approximately $67 million USD (¥7.4 billion JPY) over five years. Estimated cost savings associated with BAY 94-9027 ranged from $1.4 million USD (¥156 million JPY) in 2020 to $23 million USD (¥2.6 billion JPY) in 2024 for the Japanese healthcare system. LIMITATIONS: There were limitations associated with the study. The Japanese guidelines consulted during the targeted literature review of national data sources in Japan were based on global data as reference sources. Also, studies reporting the bleeding rate, dosing guidelines, and economic burden in the Japanese population identified by the targeted literature review were limited hence global studies were used and may not have been representative of the Japanese population. CONCLUSIONS: BAY 94-9027 can reduce total severe HA treatment costs, driven by lower annual rFVIII utilization, and a narrow weekly dosing range compared to competitor products in the Japanese market.

The disease burden of mucormycosis in Japan: results from a systematic literature review and retrospective database study.

OBJECTIVE: To evaluate outcomes, healthcare resource utilization, and costs associated with mucormycosis in inpatient settings in Japan. METHODS: We performed a systematic literature review, followed by a retrospective database study using hospital health claims for patients in Japan hospitalized with a diagnosis of mucormycosis between January 2010 and January 2019. Outcomes assessed included duration of index hospitalization; index stay mortality; hospital readmission within 30, 60, and 90 days after index hospitalization discharge; drug/treatment utilization and patterns; number of patients examined for mucormycosis during the index hospitalization; and index stay inpatient costs. RESULTS: From our systematic literature review of articles describing 133 patients with mucormycosis, mortality in the index hospitalization was 55.6%. From our database study of 126 patients hospitalized for mucormycosis, mortality during the index hospitalization was 35.7% and mean index stay duration was 94 days. Hematologic malignancies were the most common risk factor in the literature review and the most common comorbidity in the database study. During the index stay, 39 patients (31.0%) received liposomal amphotericin B (L-AMB) treatment and 74 patients (58.7%) received other antifungal treatments. Median total inpatient costs for the index hospitalization were equivalent to approximately US$60,945, including US$29,283 in drug costs. CONCLUSIONS: This study investigated the healthcare resource utilization and cost of medical resources caused by mucormycosis in Japan. The drug costs for antifungal treatments comprised about half of total inpatient costs. Mucormycosis leads to high mortality, high healthcare resource utilization, and high costs.