Impact of government-issued financial incentive to medical facilities on management of secondary dysmenorrhea.

AIM: In April 2020, the Japanese government introduced a Specific Medical Fee for managing secondary dysmenorrhea (SD). This initiative provided financial incentives to medical facilities that provide appropriate management of SD with hormonal therapies. We aimed to assess how this policy affects the management processes and outcomes of patients with SD. METHODS: Using a large Japanese administrative claims database, we identified outpatient visits of patients diagnosed with SD from April 2018 to March 2022. We used an interrupted time-series analysis and defined before April 2020 as the pre-introduction period and after April 2020 as the post-introduction period. Outcomes were the monthly proportions of outpatient visits due to SD and hormonal therapy among women in the database and the proportions of outpatient visits for hormonal therapy and continuous outpatient visits among patients with SD. RESULTS: We identified 815 477 outpatient visits of patients diagnosed with SD during the pre-introduction period and 920 183 outpatient visits during the post-introduction period. There were significant upward slope changes after the introduction of financial incentives in the outpatient visits due to SD (+0.29% yearly; 95% confidence interval, +0.20% to +0.38%) and hormonal therapies (+0.038% yearly; 95% confidence interval, +0.030% to +0.045%) among the women in the database. Similarly, a significant level change was observed after the introduction of continuous outpatient visits among patients with SD (+2.68% monthly; 95% confidence interval, +0.87% to +4.49%). CONCLUSIONS: Government-issued financial incentives were associated with an increase in the number of patients diagnosed with SD, hormonal therapies, and continuous outpatient visits.

Epidemiology of patients with lymphangioleiomyomatosis: A descriptive study using the national database of health insurance claims and specific health checkups of Japan.

BACKGROUND: Using patient registries or limited regional hospitalization data may result in underestimation of the incidence and prevalence of rare diseases. Therefore, we used the national administrative database to estimate the incidence and prevalence of lymphangioleiomyomatosis over six years (2014-2019) and describe changes in clinical practice and mortality. METHODS: We extracted data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan between January 2013 and December 2020. This database covers ≥99% of the population. We used the diagnostic code for lymphangioleiomyomatosis to estimate the incidence and prevalence from 2014 to 2019. Additionally, we examined the demographic characteristics, treatments, comorbidities, and mortality of the patients. RESULTS: In women, the incidence and prevalence of lymphangioleiomyomatosis in 2019 were approximately 3 per 1,000,000 person-years and 28.7 per 1,000,000 persons, respectively. While, in men, the incidence and prevalence of lymphangioleiomyomatosis were <0.2 per 1,000,000 person-years and 0.8 per 1,000,000 persons, respectively. From 2014 to 2019, the proportion of prescriptions of sirolimus and everolimus increased, while the use of home oxygen therapy, chest drainage, comorbid pneumothorax, and bloody phlegm decreased. The mortality rate remained stable at approximately 1%. CONCLUSIONS: The incidence and prevalence of lymphangioleiomyomatosis were higher in women than those reported previously. Although the incidence did not change during the 6-year period, the prevalence gradually increased. Moreover, lymphangioleiomyomatosis was observed to be rare in men. The practice of treating patients with lymphangioleiomyomatosis changed across the six years while mortality remained low, at approximately 1%.

Exploring the influence of a financial incentive scheme on early mobilization and rehabilitation in ICU patients: an interrupted time-series analysis.

BACKGROUND: Clinical guidelines recommend early mobilization and rehabilitation (EMR) for patients who are critically ill. However, various barriers impede its implementation in real-world clinical settings. In 2018, the Japanese universal healthcare coverage system announced a unique financial incentive scheme to facilitate EMR for patients in intensive care units (ICU). This study evaluated whether such an incentive improved patients' activities of daily living (ADL) and reduced their hospital length of stay (LOS). METHODS: Using the national inpatient database in Japan, we identified patients admitted to the ICU, who stayed over 48 hours between April 2017 and March 2019. The financial incentive required medical institutions to form a multidisciplinary team approach for EMR, development and periodic review of the standardized rehabilitation protocol, starting rehabilitation within 2 days of ICU admission. The incentive amounted to 34.6 United States Dollars per patient per day with limit 14 days, structured as a per diem payment. Hospitals were not mandated to provide detailed information on individual rehabilitation for government, and the insurer made payments directly to the hospitals based on their claims. Exposure was the introduction of the financial incentive defined as the first day of claim by each hospital. We conducted an interrupted time-series analysis to assess the impact of the financial incentive scheme. Multivariable radon-effects regression and Tobit regression analysis were performed with random intercept for the hospital of admission. RESULTS: A total of 33,568 patients were deemed eligible. We confirmed that the basic assumption of ITS was fulfilled. The financial incentive was associated with an improvement in the Barthel index at discharge (0.44 points change in trend per month; 95% confidence interval = 0.20-0.68) and shorter hospital LOS (- 0.66 days change in trend per month; 95% confidence interval = - 0.88 - -0.44). The sensitivity and subgroup analyses showed consistent results. CONCLUSIONS: The study suggests a potential association between the financial incentive for EMR in ICU patients and improved outcomes. This incentive scheme may provide a unique solution to EMR barrier in practice, however, caution is warranted in interpreting these findings due to recent changes in ICU care practices.

Optimal age to discontinue long-term surveillance of intraductal papillary mucinous neoplasms: comparative cost-effectiveness of surveillance by age.

OBJECTIVE: Current guidelines recommend long-term image-based surveillance for patients with low-risk intraductal papillary mucinous neoplasms (IPMNs). This simulation study aimed to examine the comparative cost-effectiveness of continued versus discontinued surveillance at different ages and define the optimal age to stop surveillance. DESIGN: We constructed a Markov model with a lifetime horizon to simulate the clinical course of patients with IPMNs receiving imaging-based surveillance. We calculated incremental cost-effectiveness ratios (ICERs) for continued versus discontinued surveillance at different ages to stop surveillance, stratified by sex and IPMN types (branch-duct vs mixed-type). We determined the optimal age to stop surveillance as the lowest age at which the ICER exceeded the willingness-to-pay threshold of US$100 000 per quality-adjusted life year. To estimate model parameters, we used a clinical cohort of 3000 patients with IPMNs and a national database including 40 166 patients with pancreatic cancer receiving pancreatectomy as well as published data. RESULTS: In male patients, the optimal age to stop surveillance was 76-78 years irrespective of the IPMN types, compared with 70, 73, 81, and 84 years for female patients with branch-duct IPMNs <20 mm, =20-29 mm, ≥30 mm and mixed-type IPMNs, respectively. The suggested ages became younger according to an increasing level of comorbidities. In cases with high comorbidity burden, the ICERs were above the willingness-to-pay threshold irrespective of sex and the size of branch-duct IPMNs. CONCLUSIONS: The cost-effectiveness of long-term IPMN surveillance depended on sex, IPMN types, and comorbidity levels, suggesting the potential to personalise patient management from the health economic perspective.

Machine Learning-based Models for Outpatient Prescription of Kampo Formulations: An Analysis of a Health Insurance Claims Database.

BACKGROUND: Despite the widespread practice of Japanese traditional Kampo medicine, the characteristics of patients receiving various Kampo formulations have not been documented in detail. We applied a machine learning model to a health insurance claims database to identify the factors associated with the use of Kampo formulations. METHODS: A 10% sample of enrollees of the JMDC Claims Database in 2018 and 2019 was used to create the training and testing sets, respectively. Logistic regression analyses with lasso regularization were performed in the training set to construct models with prescriptions of 10 commonly used Kampo formulations in 1 year as the dependent variable and data of the preceding year as independent variables. Models were applied to the testing set to calculate the C-statistics. Additionally, the performance of simplified scores using 10 or 5 variables were evaluated. RESULTS: There were 338,924 and 399,174 enrollees in the training and testing sets, respectively. The commonly prescribed Kampo formulations included kakkonto, bakumondoto, and shoseityuto. Based on the lasso models, the C-statistics ranged from 0.643 (maoto) to 0.888 (tokishakuyakusan). The models identified both the common determinants of different Kampo formulations and the specific characteristics associated with particular Kampo formulations. The simplified scores were slightly inferior to full models. CONCLUSION: Lasso regression models showed good performance for explaining various Kampo prescriptions from claims data. The models identified the characteristics associated with Kampo formulation use.

Cost-effectiveness analysis of prophylactic laser peripheral iridotomy for primary angle-closure suspect in Japan.

BACKGROUND/OBJECTIVES: This study aimed to compare the cost-effectiveness of prophylactic laser peripheral iridotomy (LPI) with that of observation for primary angle-closure suspect (PACS) in Japan. SUBJECTS/METHODS: A Markov model was developed to compare the costs and utilities of prophylactic LPI with those of observation of 40-year-old patients with PACS. In the model with a yearly cycle over a 20-year time horizon, the disease was postulated to irreversibly progress from PACS to primary angle closure, followed by primary angle-closure glaucoma, unilateral blindness, and bilateral blindness. The parameters were estimated mainly based on a recent randomised controlled trial and analyses of Japanese claims data. The incremental cost-effectiveness ratio was estimated from the healthcare payer's perspective and evaluated at the willingness-to-pay 5 million Japanese Yen per quality-adjusted life-year. The observation period and the age at entry into the cohort was changed to account for a variety of clinical courses in sensitivity analyses. We conducted one-way deterministic sensitivity analysis and probabilistic sensitivity analysis with Monte Carlo simulations with 10 000 iterations. RESULTS: The incremental cost-effectiveness ratio of LPI was 2,287,662 Japanese Yen (14,298 pounds sterling) per quality-adjusted life-year, which was below the willingness-to-pay threshold. The ratios were approximately 4 and 8 million in the 15-year and 10-year time horizons, respectively. Increasing the age at entry had little influence on the incremental cost-effectiveness ratio. The deterministic and probabilistic sensitivity analyses indicated that the results were robust. CONCLUSIONS: Our results indicate that prophylactic LPI for middle-aged patients with PACS is cost-effective in Japan.

Incidence, management, and prognostic impact of arrhythmias in patients with Takotsubo syndrome: a nationwide retrospective cohort study.

AIMS: Arrhythmia is a major complication of Takotsubo syndrome (TTS). However, its incidence, management, and prognostic impact remain to be elucidated in a large cohort. METHODS AND RESULTS: We retrospectively identified 16 713 patients hospitalized for TTS between July 2010 and March 2021 from the Japanese Diagnosis Procedure Combination database. Serious arrhythmias were defined as ventricular tachycardia/fibrillation (VT/VF), 2nd-/3rd-degree atrioventricular block (AVB), sick sinus syndrome (SSS), or unspecified arrhythmias requiring device treatment. Patient characteristics and outcomes were compared based on the occurrence of serious arrhythmias. The overall incidence proportion of serious arrhythmias was 6.2% (n = 1036; 449 VT/VF, 283 2nd-/3rd-degree AVB, 133 SSS, 55 multiple arrhythmias, 116 others), which remained stable over 11 years. The arrhythmia group was younger, more often male, and exhibited greater impairment in activities of daily living (ADLs) and consciousness than the non-arrhythmia group. Although crude in-hospital mortality was higher in the arrhythmia group (9.6% vs. 5.0%, P < 0.001), the significant association between arrhythmias and mortality disappeared after adjustment for confounders (odds ratio = 1.15, 95% confidence interval = 0.90-1.49). Meanwhile, age, sex, ADLs, consciousness level, and Charlson comorbidity index were significantly associated with mortality. In the arrhythmia group, 254 (24.5%) patients received pacemakers (18.4%) or defibrillators (6.1%), which were implanted at a median of 8 and 19 days after admission, respectively. CONCLUSION: Arrhythmias are not uncommon in TTS. Patients' background characteristics, rather than arrhythmia itself, may be associated with in-hospital mortality. Given the reversibility of cardiac dysfunction in TTS, there may be unnecessary device implantations for arrhythmias occurring as sequelae to TTS, warranting further investigations.

Impact of a financial incentive scheme for team-based palliative care in patients with heart failure in Japan: A nationwide database study.

BACKGROUND: Palliative care provided to patients with heart failure (HF) are reported to be inadequate. Herein, we examined the impact of the recently introduced financial incentive scheme for team-based palliative care for patients with HF in acute care hospitals in Japan. METHODS: Using a nationwide inpatient database, we identified patients aged ≥65 years with HF who had died between April 2015 and March 2021. Interrupted time-series analyses were used to compare practice patterns in end-of-life care (symptom management and invasive medical procedures within one week before death) before and after the financial incentive scheme issuance in April 2018. RESULTS: Overall, 53,857 patients in 835 hospitals were eligible. The adoption of the financial incentive was 1.10 to 1.22% after the introduction. There were upward pre-trends in opioid use (+0.11% per month; 95% confidence interval [CI], 0.06 to 0.15) and antidepressant use (+0.06% per month; 95% CI, 0.04 to 0.09). Opioid use showed a downward slope change during the post-period (-0.07% change in trend; 95% CI, -0.13 to -0.01). Intensive care unit stay showed a downward pre-trend (-0.09% per month; 95% CI, -0.14 to -0.04) and upward slope changes during the post-period (+0.12% change in trend; 95% CI, 0.04 to 0.19). Invasive mechanical ventilation showed downward slope changes during the post-period (-0.11% change in trend; 95% CI, -0.18 to -0.04). CONCLUSIONS: The financial incentive scheme for team-based palliative care was rarely adopted and not associated with changes in end-of-life care. Further multifaceted strategies to promote palliative care for HF are warranted.

Practice patterns and costs of glaucoma treatment in Japan.

PURPOSE: Understanding the practice patterns and costs of glaucoma care in real-world clinical settings is important for optimizing medical expenses. However, glaucoma treatment trends and associated costs in Japan are unknown. We aimed to unveil glaucoma treatment trends and costs using a large administrative claims database in Japan. STUDY DESIGN: Retrospective cohort study. METHODS: We included patients diagnosed with glaucoma between April 2014 and March 2021 using the DeSC database. We calculated the frequencies and costs of antiglaucoma eyedrops, incisional or laser procedures, and ophthalmic examinations stratified by fiscal year and age. In the year-by-year analyses, the age distribution was standardized based on the 2020 distribution. RESULTS: A total of 841,747 patient-years (429,051 patients) were included. The number of prescribed eyedrops significantly increased and the fixed-combination eyedrops proportion decreased with age. Trabeculectomy frequency decreased, and that of laser trabeculoplasty increased during the observation period. The frequencies of both incisional and laser procedures peaked in the 75-79 age group. In 2020, 16.1 bottles of eyedrops per patient-year were prescribed, and 15.9 incisional surgeries and 11.3 laser therapies were performed per 1000 patient-years. Intraocular pressure measurement and visual field testing were performed 6.5 times and 2.0 times per patient-year, respectively. The total direct cost of glaucoma treatment was 55,139 yen (US $399.5) per patient-year, of which medications accounted for 44.2%, ophthalmic examinations for 47.4%, and incisional or laser procedures for 8.4%. CONCLUSION: These results may be useful for understanding glaucoma treatment trends and costs in Japan.

Effectiveness of medical fee revisions for psychotropic polypharmacy in patients with mood disorders in Japan: An interrupted time-series analysis using a nationwide inpatient database.

BACKGROUND: This study aimed to evaluate the effects of medical fee revisions aimed to reduce psychotropic polypharmacy in Japan on the proportion of psychotropic polypharmacy in discharge prescriptions for patients with major depressive disorder (MDD) or bipolar disorder (BD) using a nationwide inpatient database. METHODS: In this retrospective cohort study, we used the Diagnosis Procedure Combination database to identify patients with MDD or BD discharged between April 2012 and March 2021. We targeted medical fee revisions in October 2014, April 2016, and April 2018. The major outcome was the monthly proportion of psychotropic polypharmacy in prescription at discharge using the criteria following the April 2018 revision (antidepressants ≥3, antipsychotics ≥3, anxiolytics ≥3, hypnotics ≥3, or sum of anxiolytics and hypnotics ≥4). We performed interrupted time series analyses to evaluate the changes in level and trend between pre- and post-revisions. RESULTS: We identified 63,289 and 33,780 patients with MDD and BD respectively in the entire study period. In both the patient groups, there were significant decreases in the proportion of psychotropic polypharmacy at revision in October 2014, and no significant trend and level change at revision were observed in April 2016 and April 2018, with a few exceptions. CONCLUSIONS: The medical fee revisions aimed to reduce psychotropic polypharmacy in Japan might have had a limited impact on discharge prescriptions for patients with MDD and BD.

Association Between Levels of Intensive Care and In-Hospital Mortality in Patients Hospitalized for Sepsis Stratified by Sequential Organ Failure Assessment Scores.

OBJECTIVES: To assess the association between levels of intensive care and in-hospital mortality in patients hospitalized for sepsis, stratified by Sequential Organ Failure Assessment (SOFA) score at admission. DESIGN: A nationwide, propensity score-matched, retrospective cohort study. SETTING: A Japanese national inpatient database with data on 70-75% of all ICU and high-dependency care unit (HDU) beds in Japan. PATIENTS: Adult patients hospitalized for sepsis with SOFA scores greater than or equal to 2 on their day of admission between April 1, 2018, and March 31, 2021, were recruited. Propensity score matching was performed to compare in-hospital mortality, and patients were stratified into 10 groups according to SOFA scores. INTERVENTIONS: Two exposure and control groups according to treatment unit on day of admission: 1) ICU + HDU versus general ward and 2) ICU versus HDU. MEASUREMENTS AND MAIN RESULTS: Of 97,070 patients, 19,770 (20.4%), 23,066 (23.8%), and 54,234 (55.9%) were treated in ICU, HDU, and general ward, respectively. After propensity score matching, the ICU + HDU group had significantly lower in-hospital mortality than the general ward group, among cohorts with SOFA scores greater than or equal to 6. There were no significant differences in in-hospital mortality among cohorts with SOFA scores 3-5. The ICU + HDU group had significantly higher in-hospital mortality than the general ward among cohorts with SOFA scores of 2. The ICU group had lower in-hospital mortality than the HDU group among cohorts with SOFA scores greater than or equal to 12. There were no significant differences in in-hospital mortality among cohorts with SOFA scores 5-11. The ICU group had significantly higher in-hospital mortality than the general ward group among cohorts with SOFA scores less than or equal to 4. CONCLUSIONS: Patients hospitalized for sepsis with SOFA scores greater than or equal to 6 in the ICU or HDU had lower in-hospital mortality than those in the general ward, as did those with SOFA scores greater than or equal to 12 in the ICU versus HDU.

Development and validation of genome-wide polygenic risk scores for predicting breast cancer incidence in Japanese females: a population-based case-cohort study.

PURPOSE: This study aimed to develop an ancestry-specific polygenic risk scores (PRSs) for the prediction of breast cancer events in Japanese females and validate it in a longitudinal cohort study. METHODS: Using publicly available summary statistics of female breast cancer genome-wide association study (GWAS) of Japanese and European ancestries, we, respectively, developed 31 candidate genome-wide PRSs using pruning and thresholding (P + T) and LDpred methods with varying parameters. Among the candidate PRS models, the best model was selected using a case-cohort dataset (63 breast cancer cases and 2213 sub-cohorts of Japanese females during a median follow-up of 11.9 years) according to the maximal predictive ability by Harrell's C-statistics. The best-performing PRS for each derivation GWAS was evaluated in another independent case-cohort dataset (260 breast cancer cases and 7845 sub-cohorts of Japanese females during a median follow-up of 16.9 years). RESULTS: For the best PRS model involving 46,861 single nucleotide polymorphisms (SNPs; P + T method with PT = 0.05 and R2 = 0.2) derived from Japanese-ancestry GWAS, the Harrell's C-statistic was 0.598 ± 0.018 in the evaluation dataset. The age-adjusted hazard ratio for breast cancer in females with the highest PRS quintile compared with those in the lowest PRS quintile was 2.47 (95% confidence intervals, 1.64-3.70). The PRS constructed using Japanese-ancestry GWAS demonstrated better predictive performance for breast cancer in Japanese females than that using European-ancestry GWAS (Harrell's C-statistics 0.598 versus 0.586). CONCLUSION: This study developed a breast cancer PRS for Japanese females and demonstrated the usefulness of the PRS for breast cancer risk stratification.

Recent Trends in Treatment and Associated Costs of Primary Angle-Closure Glaucoma: A Retrospective Cohort Study.

PURPOSE: To describe recent trends in the treatment for primary angle-closure glaucoma (PACG) and its associated costs in a clinical setting. DESIGN: A retrospective cohort study. SUBJECTS: We included patients with PACG from 2011 to 2020 using a large-scale administrative claims database in Japan. METHODS: We calculated the frequencies and costs of antiglaucoma drugs, ophthalmic examinations, and glaucoma-related surgeries, stratified by fiscal years and age groups. MAIN OUTCOME MEASURES: Frequencies and costs of antiglaucoma drugs, ophthalmic examinations, and glaucoma-related surgeries. RESULTS: We identified 5654 patients with PACG (15 338 patient-years). Prostanoid FP receptor agonist, nonselective ß-blocker, and topical carbonic anhydrase inhibitor use decreased, whereas prostanoid EP2 receptor agonist, α-2 adrenergic agonist, Rho-associated protein kinase inhibitor, and fixed-combination eyedrops use increased. The total amount of drug per patient-year significantly decreased. In recent years, the frequency of cataract surgery increased, whereas that of laser peripheral iridotomy decreased. Visual field testing, slit-lamp examination, intraocular pressure measurement, and funduscopy were performed 0.83, 6.65, 5.15, and 4.61 times/patient-year, respectively. The total cost of drugs, examinations, and surgeries was 60 338 yen per patient-year. Patients with PACG spent more than twice the money on surgeries and examinations than they did on antiglaucoma drugs. CONCLUSION: The amount of antiglaucoma drugs dispensed decreased, and the proportion of fixed-combination and newly introduced eyedrops increased. Frequency of cataract surgery increased whereas that of laser peripheral iridotomy decreased in recent years. Surgeries and examinations were the major cost drivers for PACG treatment. The current results would be valuable information for future economic analyses and policy making. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Short-term effects of reduced cost sharing on childhood dental care utilization and dental caries prevention in Japan.

OBJECTIVES: Generous dental insurance coverage can improve oral health among children. However, most previous studies were from the United States, and the results may not be applicable to countries with universal healthcare systems. The purpose of the present study was to examine the effect of dental subsidy on dental service utilization and oral health among school-aged children. METHODS: An administrative claims database in Kumamoto Prefecture, Japan, between 2014 and 2015 was used for the study. Municipalities in which the upper age limit of qualification for the dental subsidy was either 9 years of age or older were selected. The difference-in-differences approach was used to investigate the impact of subsidy discontinuation on dental care utilization and dental caries prevention. Dental care utilization was measured by number of first visits, number of total visits, and dental care cost per visit. Failure in dental caries prevention was determined by identifying treatment for acute severe dental conditions. RESULTS: During the study period, 1108 eligible children made a total of 6276 visits to the 455 selected dental clinics. Among the dental clinics, 230 (50.5%) were located in municipalities in which the dental subsidy was discontinued when children reached age 10. After adjusting for area income and minimal user charges, there were no significant differences in subsequent dental care utilization (mean ratio 1.01, 95% confidence interval [CI] 0.97-1.04 for first visits; mean ratio 1.01, 95% CI 0.98-1.05 for total visits), acute severe dental conditions (mean ratio 1.06, 95% CI 0.90-1.24) or cost (coefficient 0.7 US dollars; 95%CI -0.2-1.6) during the 12-month period following the policy change. CONCLUSION: The current dental subsidy policy may have limited value for promoting dental care utilization and improving oral health among school-aged children in Japan.

One-year costs of incisional glaucoma surgery and laser therapy.

BACKGROUND: This study aimed to calculate one-year total costs of incisional glaucoma surgery and laser therapy in a real-world clinical setting. METHODS: We conducted a retrospective cohort study from July 2010 to March 2021 using the Diagnosis Procedure Combination database. We included patients hospitalized for incisional glaucoma surgery (trabeculectomy, trabeculotomy, tube shunt surgery, Ex-PRESS surgery, or iStent implantation) or laser therapy (laser peripheral iridotomy, surgical iridectomy, laser trabeculoplasty, cyclocryotherapy, or cyclophotocoagulation). The outcomes were total costs, including costs of hospitalization, re-admissions, antiglaucoma drugs, ophthalmic examinations, and outpatient visits for incisional glaucoma surgery and laser therapy within one year. RESULTS: We identified 49,202 eligible hospitalizations. The one-year median total cost was 707,497 yen [interquartile range: 546,887-944,664 yen]. The median total cost was the highest in patients undergoing tube shunt surgery, followed by Ex-PRESS surgery, iStent implantation, and trabeculectomy. The number and cost of postoperative outpatient visits and length of hospital stay were higher in patients who underwent trabeculectomy and Ex-PRESS surgery than in those after tube shunt surgery. The total costs of laser therapies were lower than those of incisional glaucoma surgeries. The total cost was the highest in the 0-19 age group (856,398 [649,419-1,258,844] yen). CONCLUSIONS: Tube shunt surgery was the costliest in terms of total one-year costs. Trabeculectomy and Ex-PRESS surgery were associated with long hospital stays and incurred high postoperative costs. The costs of laser therapies were relatively low. However, cost-effectiveness of laser therapies compared with incisional surgeries needs to be analyzed in future research.

Current status of health technology assessment research in Japan.

Health technology assessment (HTA) is implemented in the decision-making process for the reimbursement and pricing of drugs and medical devices around the world. This study presented the trend and characteristics of HTA research in Japan and worldwide. HTA research increased since the 2010s. Cancer was a prominent subject and the Markov model was a major analytical model in HTA research both globally and in Japan. In Japan, osteoporosis was a more popular topic, but there were fewer surgical research and review articles compared to the global trend. Since Japanese articles on HTA were much fewer than those from the United States, the United Kingdom, and China, various types of HTA research should be encouraged in Japan to promote product innovation and optimize medical expenditures.

A post-marketing safety assessment of COVID-19 mRNA vaccination for serious adverse outcomes using administrative claims data linked with vaccination registry in a city of Japan.

INTRODUCTION: The safety profiles of COVID-19 vaccines are incompletely evaluated in Japan. OBJECTIVES: To examine the risk of serious adverse effects after COVID-19 mRNA vaccination (BNT162b2 and mRNA-1273) in cohort studies and self-controlled case series (SCCS). METHODS: Using an administrative claims database linked with the COVID-19 vaccination registry in a city in Japan between September 2020 and September 2021, we identified health insurance enrolees aged ≥ 18 years. We evaluated the risk of acute myocardial infarction, appendicitis, Bell's palsy, convulsions/seizures, disseminated intravascular coagulation, immune thrombocytopenia, pulmonary embolism, haemorrhagic or ischemic stroke, venous thromboembolism, and all-cause mortality, 21 days following any COVID-19 mRNA vaccination, compared with non-vaccination periods. For the cohort studies, we estimated incidence rate ratios (IRRs) by Poisson regression and rate differences (IRDs) by weighted least-squares regression, adjusting for sex, age, and Charlson comorbidity index. We applied a modified SCCS design to appropriately treat outcome-dependent exposures. For the modified SCCS, we estimated within-subject IRRs by weighted conditional Poisson regression. Subgroup analyses stratified by sex and age were also conducted. RESULTS: We identified 184,491 enrolees [male: 87,218; mean (standard deviation) age: 64.2 (19.5) years] with 136,667 first and 127,322 s dose vaccinations. The risks of any outcomes did not increase in any analyses, except for the fact that the modified SCCS indicated an increased risk of pulmonary embolism after the first dose in women (within-subject IRR [95%CI]: 3.97 [1.18-13.32]). CONCLUSION: The findings suggested that the COVID-19 mRNA vaccine was generally safe, whilst a signal of pulmonary embolism following the first dose of the COVID-19 mRNA vaccine was observed.

Cost-effectiveness analysis of termination-of-resuscitation rules for patients with out-of-hospital cardiac arrest.

AIM: To evaluate the cost-effectiveness of practices with and without termination-of-resuscitation (TOR) rules for out-of-hospital cardiac arrest (OHCA), using an analytic model based on a nationwide population-based registry in Japan. METHODS: A combined model using a decision tree and Markov model was developed to compare costs and treatment effectiveness of three scenarios: basic life support (BLS) TOR rules (BLS-rule scenario), advanced life support (ALS) TOR rules (ALS-rule scenario), and no TOR rules (No-rule scenario). A nationwide population-based OHCA registry from January 1 to December 31, 2019 and published data were used. Analyses were performed from healthcare payers' perspectives. Life-time incremental cost-effectiveness ratio (ICER) was determined by the difference in cost between two scenarios, divided by the difference in quality adjusted life year (QALY). RESULTS: The OHCA registry included 126,271 patients (57.3% men; median age, 80 years). The BLS-rule scenario yielded lower cost and less QALY than the ALS-rule scenario and No-rule scenario. With reference to the BLS-rule scenario, the ICERs for the ALS-rule scenario and No-rule scenario were 81,000 and 98,762 USD per QALY, respectively. The BLS-rule scenario was cost-effective in 100% of simulations at the willingness-to-pay threshold in Japan (5 million JPY = 45,455 USD). The willingness-to-pay threshold higher than 80,000 and 204,000 USD were required for the ALS-rule scenario and No-rule scenarios, respectively, to be cost-effective. CONCLUSION: No-rule scenario was not cost-effective compared with BLS-rule scenario within acceptable willingness-to-pay thresholds. Further research on health economics of TOR rules is warranted to support constructive discussion on implementing TOR rules.

Association of Operative Day of the Week with the Length of Stay and Total Hospitalization Costs in Patients with Partial Mastectomy: A Nationwide Database Study in Japan.

Introduction: Length of stay (LOS) is a major concern while optimizing medical resources and costs. Hence, factors influencing LOS should be investigated. In Japan, breast cancer surgery generally involves several days of hospitalization for observation, despite few complications. We hypothesized that the day of surgery (weekday; Monday-Friday) affects LOS. Methods: Using a Japanese nationwide database, we retrospectively identified 146,610 patients who underwent partial mastectomy for stage 0-III breast cancer from July 2010 to March 2017. We conducted multivariable linear and logistic regression analyses adjusting for background characteristics (such as comorbidities and hospital characteristics) with a generalized estimating equation for within-hospital clustering to compare postoperative and total LOS, total hospitalization costs, and postoperative complications between the groups for whom the surgery was performed on different days of the week. Results: In total, whereas the median postoperative LOS was 4 days (interquartile range, 3-6 days), the median total LOS was 6 days (5-8 days). The median total hospitalization cost was 6,189 US dollars (5,609-6,668 US dollars), and postoperative complications occurred in 3.3% of cases. Despite no significant difference in postoperative complications, Monday-Wednesday surgeries showed significantly shorter postoperative LOS than Friday surgeries (-0.11 days [95% confidence interval, -0.14 to -0.07] on Monday with reference to Friday). Nevertheless, Monday surgeries showed significantly increased total LOS (0.69 days [0.64-0.74]) and hospitalization costs (93 US dollars [71-116]) in comparison with Friday surgeries. Conclusions: The operative day of the week was associated with increased LOS and cost, with no difference in postoperative complications after partial mastectomy. Surgeries on Monday involved longer preoperative hospital stays and higher total hospitalization costs than those on other weekdays.

Cost-effectiveness analysis of trastuzumab monotherapy versus adjuvant chemotherapy plus trastuzumab in elderly patients with HER2-positive early breast cancer.

BACKGROUND: In elderly patients with human epidermal growth factor 2-positive breast cancer, adjuvant chemotherapy was associated with decreased quality of life, with relatively small benefits for prognosis. We examined the cost-effectiveness of trastuzumab monotherapy versus adjuvant chemotherapy plus trastuzumab in elderly patients with human epidermal growth factor 2-positive breast cancer. METHODS: A Markov model was developed to evaluate the costs and benefits of trastuzumab monotherapy over adjuvant chemotherapy plus trastuzumab for elderly patients with human epidermal growth factor 2-positive breast cancer. We built the model with a yearly cycle over a 20-year time horizon and five health states: disease-free, relapse, post-relapse, metastasis and death. The parameters in the model were based on a previous randomized controlled trial and a nationwide administrative database in Japan. The incremental cost-effectiveness ratio, expressed as Japanese yen per the quality-adjusted life-years, was estimated from the perspective of health care payers. One-way deterministic sensitivity analysis and probabilistic sensitivity analysis with Monte-Carlo simulations of 10 000 samples were conducted. RESULTS: The incremental cost-effectiveness ratio of trastuzumab monotherapy over adjuvant chemotherapy plus trastuzumab was $\sim$1.8 million Japanese yen /quality-adjusted life-year. The one-way deterministic sensitivity analysis showed that transition probability from disease-free to metastasis status and cost of metastasis status had the greatest influence on the incremental cost-effectiveness ratio. More than half the estimates in the probabilistic sensitivity analysis were located below a threshold of willingness-to-pay of 5 million Japanese yen /quality-adjusted life-year. CONCLUSION: In this first comparative cost-effectiveness analysis of adjuvant chemotherapy plus trastuzumab versus trastuzumab monotherapy in the elderly, the latter was found favorable for elderly patients with human epidermal growth factor 2-positive breast cancer.