Opioid prescriptions at the point of surgery, bone metastasis, or death among patients with breast cancer in Japanese acute care hospitals: a claims-based, retrospective, longitudinal study.

PURPOSE: Breast cancer is the most common cancer among Japanese women and often yields a better prognosis than other cancers. However, few studies have been conducted on pain control using opioids in Japan. In this study, we aimed to examine actual opioid use among breast cancer patients. METHODS: Breast cancer patients were defined as female patients with a first breast cancer diagnosis during the observational period in an acute care hospital database (April 2008 - February 2020). We examined the percentage of patients prescribed opioids, the opioid amount per patient, and the opioid dosage per day around surgery, bone metastasis diagnosis, or death. RESULTS: Overall, 217,722 breast cancer patients were identified. The percentage of patients prescribed opioids and the average amount of opioids per patient were highest in the month of surgery, 78% and 27 morphine milligram equivalents (MMEs), respectively. The average opioid dosage increased with time after surgery from 19 to 28 MMEs. Around bone metastasis, the percentage of patients prescribed opioids and the average opioid amount per patient peaked one month after the diagnosis, 31% and 371 MMEs, respectively. The average opioid dosage gradually increased from 22 to 35 MMEs in succeeding days after a bone metastasis diagnosis. The percentage of patients prescribed opioids and the average opioid amount per patient increased as the month of death approached. CONCLUSION: We investigated opioid prescription trends around clinical events in breast cancer patients on a large scale in Japan. These results may be useful to control cancer pain among breast cancer patients.

Prevalence of idiopathic pulmonary fibrosis in Japan based on a claims database analysis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a cryptogenic chronic interstitial pneumonia with progressive fibrosis and a poor prognosis. A substantial number of epidemiological studies have been conducted in Europe and the United States (US). In contrast, in Japan, only one study reported the prevalence of IPF (10.0 per 100,000 population) using clinical data (2003-2007) from one prefecture; thus, the nationwide prevalence of IPF remains unknown. This study aimed to estimate the nationwide prevalence of IPF in Japan using a nationwide claims database. METHODS: We extracted data from a Japanese claims database provided by Medical Data Vision (MDV database, April 2008-March 2019) containing data from approximately 28 million patients from 385 acute-care hospitals. Patients with IPF (those diagnosed with IPF at least once) from April 2017 to March 2018 were identified in the MDV database. The number of patients in the MDV database was extrapolated nationwide using the fourth NDB Open Data (April 2017-March 2018), and the prevalence was estimated using demographic data as denominators. The prevalence in the US, considering the same definition of IPF, was also calculated and compared with that in Japan. RESULT: The number of patients with IPF in the MDV database was 4278. The estimated nationwide number of patients in Japan was estimated to be 34,040 (mean age: 73 years, percentage of men: 73%), and the prevalence was 27 per 100,000 population. In comparison with that in the US, the prevalence was similar in men and relatively lower in women until the age of 75-79 years, and it was notably lower in both sexes aged ≥ 80 years. CONCLUSIONS: We report the nationwide IPF prevalence in Japan using data from claims databases for the first time. The prevalence estimated in this study was higher than that reported in a previous study. The difference might be due to differences in study settings and definitions of IPF. Further research should be performed to determine the prevalence more accurately and compare it with those in other countries.

Recent transition of medical cost and relapse rate of multiple sclerosis in Japan based on analysis of a health insurance claims database.

BACKGROUND: In this study, we aimed to understand the trends in total and itemized medical expenses, especially of disease-modifying therapy (DMT), for multiple sclerosis (MS) in Japan through an analysis of health insurance claims data. METHODS: We analyzed a database containing health insurance claims data from hospitals that have adopted the Diagnosis Procedure Combination/Per-Diem Payment System in Japan. According to an algorithm based on diagnosis codes, data for all patients diagnosed with MS from April 2008 to July 2016 were extracted. Medical costs, rate of each medical treatment, and rate of relapses were analyzed by calendar-year. Medical costs in the month of relapse were compared with average medical costs per month of all MS patients by a cross-sectional analysis. RESULTS: Four thousand three hundred seventy-four MS patients were identified in the database. Total medical cost per patient per month (PPPM) increased from ¥87,640 (US$787.7 or €723.0 as of May 2017) to ¥102,846 (US$924.4 or €848.4) during the study period. This increment was mainly attributed to the growth in cost of outpatient DMT prescriptions, which increased from ¥23,039 (US$207.1 or €190.1) to ¥51,351 (US$461.5 or €423.6). In contrast, the rate of hospitalizations and relapses PPPM decreased during the study period (from 0.053 to 0.030, and 0.032 to 0.019, respectively). Medical costs in the month of relapse (¥424,661, US$3816.8 or €3503.1) were 3.57 times higher than the average monthly costs for all MS patients (¥119,021, US$1069.8 or €981.8), with the majority comprising hospitalization cost. CONCLUSION: Concomitant with the increased usage of DMT, the total medical cost for treating MS is increasing in Japan. However, rates of relapse and hospitalization have shown a decreasing trend. Although this study does not show the direct causality between DMT and reduction of relapse rates/fewer hospitalizations among MS patients, a reduction in hospital costs has been revealed concomitantly with the increasing prevalence of DMT.

Persistence of oral antidiabetic treatment for type 2 diabetes characterized by drug class, patient characteristics and severity of renal impairment: A Japanese database analysis.

AIM: To evaluate the persistence with oral antidiabetic drug (OAD) treatment characterized by drug class, patient characteristics and severity of renal impairment (RI) in patients with type 2 diabetes (T2DM) in Japan. MATERIALS AND METHODS: This retrospective, observational study extracted data from a large-scale hospital database (April 2008 to September 2016). Patients with T2DM aged ≥40 years on the day of their first prescription (index date) of any OAD (biguanides [BGs], thiazolidinediones [TZDs], sulphonylureas [SUs], glinides, dipeptidyl peptidase-4 [DPP-4] inhibitors, or α-glucosidase inhibitors [α-GIs]) available between January 1, 2014 and September 30, 2016 were identified. Sodium-glucose co-transporter-2 inhibitors were not available at study initiation. Treatment persistence was assessed by Kaplan-Meier survival curves. Patients were also categorized by RI status using estimated glomerular filtration rate: ≥90 mL/min/1.73 m2 (G1); 60 to <90 mL/min/1.73 m2 (G2); 30 to <60 mL/min/1.73 m2 (G3); and <30 mL/min/1.73 m2 (G4+). RESULTS: We identified 206 406 index dates from 162 116 eligible patients. The largest number of index dates (91634) was observed for DPP-4 inhibitors, followed by BGs, SUs, α-GIs, glinides and TZDs. Treatment persistence was longest for DPP-4 inhibitors (median 17.0 months, 95% confidence interval [CI] 16.4-17.5) and BGs (median 17.3 months, 95% CI 16.6-18.2), and shortest for α-GIs (median 5.6 months, 95% CI 5.4-5.9) and SUs (median 4.3 months, 95% CI 4.2-4.6). Persistence was longest with DPP-4 inhibitors at all RI stages (G1-G4+), followed by BGs at stages G1/G2. CONCLUSIONS: The longest OAD persistence was observed for BGs and DPP-4 inhibitors at RI stages G1/G2, and for DPP-4 inhibitors at RI stages G3/G4+.

Persistence rates and medical costs of biological therapies for psoriasis treatment in Japan: a real-world data study using a claims database.

BACKGROUND: Biological therapies (BTs) including infliximab (IFX), adalimumab (ADL), secukinumab (SCK) and ustekinumab (UST) are approved in Japan for the treatment of psoriasis. Although the persistence rates and medical costs of BTs treatment have been investigated in multiple foreign studies in recent years, few such studies have been conducted in Japan and the differences between patients who adhered to treatment and those who did not have not been reported. This study is aimed at investigating the persistence rates and medical costs of BTs in the treatment of psoriasis in Japan, using the real-world data from a large-scale claims database. METHODS: Claims data from the JMDC database (August 2009 to December 2016) were used for this analysis. Patient data were extracted using the ICD10 code for psoriasis and claims records of BT injections. Twelve-month and 24-month persistence rates of BTs were estimated by Kaplan-Meier methodology, and 12-month-medical costs before and after BT initiation were compared between persistent and non-persistent patient groups at 12 months. RESULTS: A total of 205 psoriasis patients treated with BTs (BT-naïve patients: 177) were identified. The 12-month/24-month persistence rates for ADL, IFX, SCK, and UST in BT-naïve patients were 46.8% ± 16.6%/46.8 ± 16.6%, 53.0% ± 14.9%/41.0% ± 15.5%, 55.4%/55.4% (95% CI not available) and 79.4% ± 9.9%/71.9% ± 12.2%, respectively. Statistically significant differences in persistence were found among different BT treatments, and UST was found to have the highest persistence rate. The total medical costs during the 12 months after BT initiation in BT-naïve patients were (in 1000 Japanese Yen): 2218 for ADL, 3409 for IFX, 465 for SCK, 2824 for UST (average: 2828). Compared with the 12-month persistent patient group, the total medical costs in the persistent group was higher (Δ:+ 118), but for some medications such as IFX or UST cost increases were lower for persistent patients. CONCLUSIONS: UST was found to have the highest persistence rate among all BTs for psoriasis treatment in Japan. The 12-month medical costs after BT initiation in the persistent patient group may not have increased as much as in the non-persistent patient group for some medications.

Selective carboxylation of reactive benzylic C-H bonds by a hypervalent iodine(III)/inorganic bromide oxidation system.

An oxidation system comprising phenyliodine(III) diacetate (PIDA) and iodosobenzene with inorganic bromide, i.e., sodium bromide, in an organic solvent led to the direct introduction of carboxylic acids into benzylic C-H bonds under mild conditions. The unique radical species, generated by the homolytic cleavage of the labile I(III)-Br bond of the in situ-formed bromo-λ3-iodane, initiated benzylic carboxylation with a high degree of selectivity for the secondary benzylic position.

Patterns of anti-vascular endothelial growth factor treatment for chorioretinal vascular diseases: Analysis of a nationwide claims database in Japan.

BACKGROUND: Although intravitreal anti-vascular endothelial growth factor therapy is currently considered the first-line treatment for chorioretinal vascular diseases in Japan, information regarding its treatment pattern is scarce. This study investigated the patterns of anti-vascular endothelial growth factor treatment for chorioretinal vascular diseases. METHODS: A health insurance claims database from acute care hospitals was used to estimate treatment intervals and continuation and drop-out rates regarding the anti-vascular endothelial growth factor. Patients aged ≥50 years diagnosed with neovascular age-related macular degeneration or aged ≥18 years diagnosed with diabetic macular edema or retinal vein occlusion were analyzed. RESULTS: Data were included for 76,535, 49,704, and 37,681 patients with neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion, respectively; exactly 8,111, 2,283, and 6,896 received the treatment, respectively. The mean and median interval ranges during the maintenance phase by treatment initiation year were 94-100 and 73-80, 111-120 and 98-102, and 97-103 and 87-93 days for neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion, respectively, without any trend over time. A tendency to increase the treatment continuation rate was indicated in later years by Kaplan-Meier curves. The drop-out rate in the treatment initiation year (2016) was 32% from 63% (2009), 53% from 69% (2014), and 36% from 47% (2013) for neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion, respectively. CONCLUSIONS: For all these diseases, the treatment intervals did not change remarkably, and a tendency toward improved treatment continuation was suggested.

Estimation of the utilities of attributes of intravenous iron infusion treatment for patients with iron-deficiency anemia: a conjoint analysis in Japan.

AIMS: This study aimed to estimate the utility values of the factors associated with intravenous (IV) iron infusion treatment in Japanese patients with iron-deficiency anemia (IDA) from the patient's perspective. METHODS: A conjoint analysis based on online survey data was conducted in May 2022 (registration number: UMIN000047756). Respondents in the main group were selected from the general population (20-69 years). Seven attributes were included in this analysis: waiting time before receiving an IV infusion, pain due to IV infusion, time required for IV infusion, number of IV infusions required to achieve treatment effect, frequency of hypophosphatemia as a side effect of IV infusion, frequency of skin discoloration by the drug solution, and out-of-pocket cost for one IV infusion visit. The utility of each level for each attribute was estimated using a logistic regression model as the difference from non-treatment. RESULTS: The responses were collected from 1,026 people. The utilities decreased with higher pain (-0.189 for pain level of 3.05), longer time for the IV infusion (-0.145 or -0.212 for 5 or 15 min), greater number of required IV infusions (-0.773 or -1.899 for 3 or 25 times), and higher frequency of adverse events (-0.373 or -0.385 for 13.0% or 14.2% of hypophosphatemia incidences; -0.502 for 2.3% of skin discoloration per one infusion). LIMITATIONS: Since this study was based on an online survey, the reliability of the results depends on whether the respondents understood the questions accurately. Further, the respondents were selected from an online panel, potentially affecting finding generalizability. CONCLUSIONS: The results indicate that utilities differ depending on the factors associated with IV iron infusion treatment. The findings of this study may be useful for informing future treatments or improving current treatment regimes, supporting the achievement of complete iron repletion for Japanese patients with IDA.

Prescription patterns and therapeutic effects of second-line drugs in Japanese patients with type 2 diabetes mellitus: Analysis of claims data for metformin and dipeptidyl peptidase-4 inhibitors as the first-line hypoglycemic agents.

BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP4is) and metformin are the most frequently prescribed first-line drugs for Japanese patients with type 2 diabetes (T2D). We investigated the risk of cardiovascular events by second-line treatment type in these patients. RESEARCH DESIGN AND METHODS: Patients with T2D, prescribed either metformin or DPP4i as a first-line drug, were identified in claims data from Japanese acute care hospitals. The primary and secondary outcomes were cumulative risks of MI or stroke and of death, respectively, from second-line treatment initiation. RESULTS: Patients prescribed first-line metformin or DPP4i was 16,736 and 74,464, respectively. In patients receiving first-line DPP4i, the death incidence was lower in those receiving second-line metformin than in those receiving second-line sulfonylurea (p < 0.001), whereas the primary outcome was not significantly different. No significant differences were observed for either outcome when DPP4is and metformin were used as first- and second-line drugs or vice versa. CONCLUSIONS: Metformin was suggested to have larger effect to reduce death than sulfonylurea in patients receiving first-line DPP4i. The order of first- and second-line for the DPP4i and metformin combination did not affect the outcomes. Given the nature of the study design, certain limitations, including potential under-adjustment for confounders, should be considered.

Estimation of Intangible Costs for Factors Associated with Oral Antiviral Drugs for COVID-19 Treatment: A Conjoint Analysis in Japan.

INTRODUCTION: During the recent coronavirus disease 2019 (COVID-19) pandemic, preferences for factors associated with vaccines have been evaluated. Three oral antiviral drugs have been approved in Japan for patients with mild-to-moderate I COVID-19 symptoms. Although preferences for the drugs may also depend on various factors, these have not been fully evaluated. METHODS: A conjoint analysis was performed based on an online survey in August 2022 to estimate the intangible costs of factors associated with oral antiviral drugs for COVID-19. Respondents were individuals aged 20-69 across Japan. The attributes included the company (Japanese/foreign) that developed the drug, formulation and size of the drug, frequency of administration per day, number of tablets/capsules per dose, number of days until no longer infectious to others, and out-of-pocket expenses. A logistic regression model was applied to estimate the utility of each level for each attribute. The intangible costs were calculated by comparing the utility to the out-of-pocket attribute. RESULTS: Responses were collected from 11,303 participants. The difference between levels was the largest for companies that developed a drug; the intangible costs were JPY 5390 higher for the foreign company than for the Japanese company. The next largest difference was in the number of days until one is no longer infectious. For the same formulation, the intangible cost was lower for small sizes than large sizes. For similar-sized tablets and capsules, the intangible cost was lower for tablets than capsules. These tendencies were similar regardless of COVID-19 infection history and the presence of risk factors for severe COVID-19 in the respondents. CONCLUSION: Intangible costs for factors associated with oral antiviral drugs among the Japanese population were estimated. The results may change as the number of people with a history of COVID-19 infection increases and significant progress is made regarding treatments.

Preferences and values for government policies on infectious disease outbreaks and epidemics for the Japanese population: a conjoint analysis.

AIMS: To investigate the preferences of the Japanese population for government policies expected to address infectious disease outbreaks and epidemics. METHODS: We performed a conjoint analysis based on survey data in December 2022 (registration number: UMIN000049665). The attributes for the conjoint analysis were policies: tests, vaccines, therapeutic drugs, behavior restrictions (e.g. self-restraint or restrictions on the gathering or travel of individuals and the hours of operation or serving of alcoholic beverages in food/beverage establishments), and entry restrictions (from abroad), and monetary attribute: an increase in the consumption tax from the current 10%, to estimate the monetary value of the policies. A logistic regression model was used for the analysis. RESULTS: Data were collected from 2,185 respondents. The accessibility of tests, vaccines, and therapeutic drugs was preferred regardless of the accessibility level. The value for accessibility of drugs to anyone at any medical facility was estimated at 4.80% of a consumption tax rate, equivalent to JPY 10.5 trillion, which was the highest among the policies evaluated in this study. The values for implementing behavior or entry restrictions were negative or lower than those for tests, vaccines, and drugs. LIMITATIONS: Respondents chosen from an online panel were not necessarily representative of the Japanese population. Because the study was conducted in December 2022, a period during the coronavirus disease 2019 (COVID-19) pandemic, the results may reflect the situation at that time and potentially be subject to rapid change. CONCLUSIONS: Among the policy options evaluated in this study, the most preferred option was easily accessible therapeutic drugs and their monetary value was substantial. Wider accessibility of tests, vaccines, and drugs was preferred over behavior and entry restrictions. We believe that the results provide information for policymaking to prepare for future infectious disease epidemics and for assessing the response to COVID-19 in Japan.

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

BACKGROUND: Valvular 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. METHODS: This 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. RESULTS: Of 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 %). CONCLUSIONS: The 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.

In-Hospital Outcomes of Heart Failure Patients with Valvular Heart Disease: Insights from Real-World Claims Data.

Purpose: Heart failure (HF) is a serious public health burden that is rapidly increasing in the aging population. Valvular heart disease (VHD) is a known etiology of heart failure (HF); however, the impact of VHD on outcomes of patients with HF has not been well-studied in Japan. This study aimed to determine the rates of VHD in Japanese patients admitted for HF and explore associations of VHD with in-hospital outcomes through a claim-based analysis. Patients and methods: We analyzed claims data from 86,763 HF hospitalizations (January 2017 through December 2019) from the Medical Data Vision database. Common etiologies of HF were examined, then hospitalizations were categorized into those with VHD and those without. Covariate-adjusted models were used to explore the association of VHD with in-hospital mortality, length of stay, and medical cost. Results: Of 86,763 hospitalizations for HF, 13,183 had VHD and 73,580 did not. VHD was the second most frequent etiology of HF (15.2%). The most frequent type of VHD was mitral regurgitation (36.4% of all hospitalizations with VHD), followed by aortic stenosis (33.7%) and aortic regurgitation (16.4%). There was no significant difference in in-hospital mortality between hospitalizations with VHD vs those without (9.0% vs 8.9%; odds ratio [95% CI]: 1.01 [0.95-1.08]; p=0.723). Hospitalizations with VHD were associated with significantly longer length of stay (26.1 vs 24.8 days; incident rate ratio [95% CI]: 1.05 [1.03-1.07]; p<0.001) and higher medical costs (1536 vs 1195 thousand yen; rate ratio [95% CI]: 1.29 [1.25-1.32]; p<0.001). Conclusion: VHD was a frequent etiology of HF that was associated with significant medical resource use. Future studies are needed to investigate whether timely VHD treatment could reduce HF progression and its associated healthcare resource utilization.

Prevalence, treatment status, medical costs, quality of life, and productivity loss in Japanese adult patients with anemia: a real-world database study.

AIMS: To investigate the prevalence, treatment status, and effect of anemia on medical costs, quality of life (QOL), and productivity loss in Japan. METHODS: This cross-sectional study used a database containing claims, health check-ups, and questionnaire data. Adults with hemoglobin data at 2020 check-ups were included. QOL and productivity loss were evaluated using EuroQol 5-Dimension (EQ-5D) and Work Productivity and Activity Impairment questionnaire data available for a subset of the population. Nationwide anemia prevalence, including both diagnosed as having anemia and undiagnosed but with low hemoglobin levels, were estimated. Treatment status was described by hemoglobin levels. Differences in medical costs, QOL, and productivity loss were compared between individuals with and without anemia. Subgroup analyses were performed using the Charlson Comorbidity Index (CCI). RESULTS: The study population included 554,798 individuals. Anemia prevalence was estimated at 15.1% with 55.3% undiagnosed. In patients with anemia, 85.3% were untreated; 79.5% of the treated patients received only oral iron drugs. In patients with anemia, monthly medical costs were ¥17,766 higher, EQ-5D score was 0.0118 lower, and productivity loss was 2.6% higher than in those without anemia. The trends were consistent even in limited patients with CCI = 0. Nationwide annual excess medical costs, deficit QOL, and productivity loss in patients with anemia were estimated at ¥3.32 trillion, 138,000 quality-adjusted life-years, and ¥1.13 trillion, respectively. LIMITATIONS: As the study population only included individuals who underwent health check-ups, they may be healthier than general population. Whether the differences in medical costs, QoL, and productivity loss are caused by anemia or other underlying differences in patient characteristics is unclear, given the likelihood of residual confounding. CONCLUSIONS: The results suggest that more than half of patients with anemia were undiagnosed and untreated. Patients with anemia had higher medical costs, lower QOL, and greater productivity loss than those without anemia.

Comparison of the effects on cardiovascular events between use of metformin and dipeptidyl peptidase-4 inhibitors as the first-line hypoglycaemic agents in Japanese patients with type 2 diabetes mellitus: a claims database analysis.

OBJECTIVES: To compare the risk of cardiovascular events from the initiation of therapy between metformin and dipeptidyl peptidase-4 inhibitors (DPP-4i) as first-line therapy. DESIGN: Retrospective cohort study using two claims databases. SETTING: The MDV database (provided by Medical Data Vision) comprised data from acute care hospitals, and the JMDC database (provided by JMDC) comprised data from individuals covered by health insurance societies. PARTICIPANTS: Those who were diagnosed with type 2 diabetes at ≥18 years, prescribed metformin or DPP-4i as the first-line hypoglycaemic agent, had medical records of ≥6 months before the index prescription and had available glycated haemoglobin (HbA1c) data for the period, including the index date and 30 days before it (defined as the baseline) were included. Those diagnosed with type 1 diabetes and/or a history of myocardial infarction (MI) or cerebrovascular diseases were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcomes were cumulative risks from Kaplan-Meier curves or HRs of patients prescribed metformin compared with DPP-4i. The primary endpoint was the diagnosis of MI or stroke associated with hospitalisation. Patient demographics, prescribed drugs and laboratory test values of HbA1c and estimated glomerular filtration rate at baseline were adjusted. The study period starting from the index included treatment after initial monotherapy. RESULTS: Overall, 2089 and 6686 patients in the MDV database and 1506 and 3635 in the JMDC database were prescribed metformin and DPP-4i, respectively. The HR of the primary endpoint was 0.879 with no statistical significance (95% CI 0.534 to 1.448, p=0.613) in the MDV database, while it was significantly lower, 0.398 (95% CI 0.213 to 0.742, 0.004) in the JMDC database. CONCLUSIONS: Patients who received metformin as first-line therapy may have reduced cardiovascular events than those receiving DPP-4i. This study conforms to previous Japanese database studies, despite the consideration of its limitation being an observational design.

Efficacy and Safety of Metformin Versus the Other Oral Antidiabetic Drugs in Japanese Type 2 Diabetes Patients: A Network Meta-analysis.

INTRODUCTION: Although metformin is recommended as a first-line treatment for patients with type 2 diabetes (T2D) in Western countries, no specific treatment is recommended in Japan, and various agents are used. Metformin has long been used at low doses in Japan, and information regarding its effect at the maximum maintenance dose is lacking. Here, we compared the efficacy and safety of metformin at 1500 mg/day with those of the other oral anti-diabetic drugs (OADs) approved in Japan. METHODS: Randomized controlled trials comparing a change in hemoglobin A1c (HbA1c) from baseline at 12 weeks or later (ΔHbA1c) among OADs (including placebo) as a first-line treatment in adult patients with T2D were selected by systematic review with comprehensive searching of CENTRAL, MEDLINE, Ichushi Web, and EMBASE and manual searching of clinical trial registries. The ΔHbA1c and incidence of hypoglycemia were compared among OAD treatments using Bayesian network meta-analysis (NMA). The relative risk (RR) of the incidence of hypoglycemia was determined relative to that of placebo. RESULTS: Forty-six randomized controlled trials were identified in the systematic review, and 37 studies, comprising 38 different types of treatments, including placebos, were selected for the NMA of ΔHbA1c. Compared with metformin 1500 mg/day, 20 OAD treatments were significantly less effective in reducing HbA1c from baseline (differences from metformin 1500 mg/day: 0.40-0.96%). Two treatments (glimepiride 2 mg/day and pioglitazone 45 mg/day) showed greater mean reductions in HbA1c from baseline than metformin 1500 mg/day (- 0.38% and - 0.03%), although these differences were not significant. Regarding the incidence of hypoglycemia, only pioglitazone 30 mg/day among 31 treatments showed a lower RR (< - 0.01), whereas 23 treatments showed a significantly higher RR (1.02-66.71) than metformin 1500 mg/day. CONCLUSION: The NMA suggested a preferable efficacy and safety profile of metformin 1500 mg/day compared with the other OADs approved in Japan.

Treatment Status and Healthcare Cost Trends for Patients with Multiple Sclerosis in Japan: A Claims Database Analysis.

INTRODUCTION: The healthcare situation of multiple sclerosis (MS) and its course are not being thoroughly investigated in Japan. We aimed to examine the current healthcare situation, including treatment and healthcare costs, of MS according to duration since its first diagnosis using Japanese real-world data to determine unidentified healthcare issues at each disease stage. METHODS: This retrospective, non-comparative, non-interventional study used a Japanese nationwide claims database (April 2008-August 2018) comprising 20 million patients from 329 acute care hospitals (as of June 2018). Treatment patterns, comorbidities, healthcare resource utilization, and healthcare costs were analyzed using longitudinal analyses of patients with MS according to duration since the first diagnosis. The time from diagnosis to first treatment was examined using Kaplan-Meier analysis. RESULTS: We identified 7067 patients with MS [mean (standard deviation) age at first diagnosis 45.0 (16.2) years]. About 70% of the patients did not receive disease-modifying therapy (DMT) within the first year of diagnosis. The frequency of DMT use decreased in patients with a longer duration since the first diagnosis. MS treatment costs tended to increase with a longer duration from the first diagnosis until 9 years, followed by a tendency to decrease; contrastingly, other healthcare costs tended to increase with duration after decreasing from the year of the first diagnosis to the next year. The frequencies of hospitalizations and hospital visits, healthcare costs-excluding those for MS treatment and tests-and prevalence of comorbidities tended to be higher in patients with a longer duration since the first diagnosis. CONCLUSION: A considerable proportion of patients did not receive DMT, suggesting that patients with early-stage MS may lose the opportunity to improve their prognosis through early intervention with DMT. Among patients with a longer duration since the first diagnosis, fewer treatment choices may be available despite the larger clinical and treatment burden.

A Principal Component Analysis Approach to Estimate the Disability Status for Patients with Multiple Sclerosis Using Japanese Claims Data.

INTRODUCTION: Claims databases are preferred for research on multiple sclerosis (MS) as this condition is characterized by low prevalence and long disease course. However, Japanese claims databases contain no information on disease severity or disability status of MS. Here, we aimed to explore the possibility of utilizing a principal component analysis (PCA) to estimate MS severity using a Japanese claims database. METHODS: An MS severity score was developed using a PCA. Factors related to functional systems for Expanded Disability Status Scale (EDSS) and higher disease severity (74 diagnoses, 68 drug prescriptions, and 77 procedures) were extracted from the claims database (April 2008-August 2018). The score (PC1 score) was developed for each patient-year-each year from the first diagnosis (excluding the year of the first diagnosis), based on the first principal component of the included factors. Finally, the patient-years were classified into quartiles based on the PC1 score, and demographic information and medical status were analyzed. RESULTS: The database contained 7067 patients with MS. The highest score group had a higher mean age (55.4 ± 0.2 [mean ± standard error] years), lower percentage of women (64.4 ± 0.7%), and longer mean disease duration from first diagnosis (8.1 ± 0.1 years) than the lowest score group (43.3 ± 0.2 years, 68.4 ± 0.8%, and 6.0 ± 0.1 years, respectively). In addition, the PC1 score of each patient positively correlated with disease duration from diagnosis. CONCLUSION: We developed a PC1 score to indicate MS severity using information from a Japanese claims database. Since changes in demographic features we observed are consistent with findings of previous research, this score might represent MS severity to some extent. Further research is necessary to validate this score with clinical measurement of disability such as the EDSS.

Burden of Repeated Hospitalizations on Patients with Heart Failure: An Analysis of Administrative and Claims Data in Japan.

BACKGROUND: Repeated hospitalization is a predictor of outcomes in heart failure, indicating the presence of symptoms, a deteriorated condition at pre-admission, and worsened prognosis. OBJECTIVES: The current database study aimed to understand the clinical and economic burden of repeated hospitalizations among patients with heart failure in Japan. The effect of repeated hospitalizations on the subsequent in-hospital mortality was the primary objective; economic burden of heart failure after discharge was investigated as a secondary outcome. METHODS: Between 2013 and 2018, administrative claims and discharge summary data of patients aged ≥ 20 years and diagnosed with heart failure were obtained from a Diagnosis Procedure Combination database maintained by Medical Data Vision. Hospitalization, mortality, and economic burden data were analyzed. RESULTS: This study included 49,094 patients. The mean length of the first hospital stay was 22.9 days. The in-hospital mortality rate was approximately 10%, with one to five repeated hospitalizations. The time interval between repeated hospitalizations for heart failure decreased with an increasing number of hospitalizations. In-hospital mortality did not increase even with an increasing number of hospitalizations. The mean heart failure-related healthcare cost per patient was ¥564,281 ± 990,447 (US$5178 ± 9,088), 67.3% of which was hospitalization costs. Among hospitalization costs, other costs were high, mainly for basic hospitalization fees (71.7%; ¥233,146/person-year). CONCLUSIONS: Repeated hospitalization did not increase in-hospital mortality; however, it may shorten the intervals between heart failure-related hospitalizations, potentially caused by deterioration of the patient's condition, and increase the clinical and economic burden on patients.

Comparison of Inconvenience Costs Between Influenza Antivirals for Japanese Pediatric Patients: A Conjoint Analysis of Parental Responses.

INTRODUCTION: Certain drug characteristics, including dosage and form, are associated with either convenience or inconvenience for the patients taking them, and any inconvenience can be considered as a "cost" in disease treatment. Multiple antivirals are available for influenza in Japan, with various dosages and forms. This study evaluated the inconvenience costs associated with influenza antivirals for pediatric patients by using conjoint analysis on responses from their parents. METHODS: An online survey (May 2021) was conducted for parents whose child took antivirals for influenza at 6-11 years during the 3 years until March 2021. Attributes of the conjoint analysis were administration routes and formulation (tablet, capsule, dry syrup, or inhalant), duration of administration, frequency of administration per day, and out-of-pocket expenses. We assumed the efficacy and safety to be equivalent among the antivirals. A logistic regression model was applied to the analysis. We also asked parents about their recent experiences with antiviral treatment for their child. RESULTS: We collected responses from 3161 eligible individuals. The mean age (standard deviation) of the children when taking the antivirals and percentage of female children were 8.27 (1.63) years old and 53.2%, respectively. The tablet was the most preferred formulation; the inconvenience costs for each administration route and formulation, relative to the tablet as zero, were Japanese yen (JPY) 515 (US dollar 4.61, as of October 2021) for the inhalant, JPY 775 for the capsule, and JPY 804 for the dry syrup. The inconvenience costs for 5 days relative to 1 day and for twice a day relative to once a day were JPY 2150 and JPY 399, respectively. CONCLUSION: Based on the conjoint analysis, a single-dose tablet antiviral was suggested to have the lowest inconvenience cost for pediatric patients. TRIAL REGISTRATION: UMIN000044243.