Cost-Effectiveness Analysis of Nivolumab Plus Ipilimumab Combination Therapy as First-line Treatment for Advanced Renal Cell Carcinoma in Japan.

OBJECTIVES: The purpose of this study is to examine the cost-effectiveness of nivolumab (NIVO) plus ipilimumab (IPI) combination therapy (NIVO + IPI) compared with the sunitinib (SUN) therapy for Japanese patients with advanced renal cell carcinoma from the perspective of a Japanese health insurance payer. METHODS: A lifetime horizon was applied, and 2% per annum was set as the discount rate. The threshold was set as $ 75 000 per quality-adjusted life-year (QALY) gained. For the analytical method, we used a partitioned survival analysis model to estimate the incremental cost-effectiveness ratio (ICER), which is calculated by dividing incremental costs by incremental QALYs. Progression-free survival, progressive disease, and death were set as health states. Additionally, cost parameters and utility weights were set as key parameters. We set the intermediate/poor-risk population as the base case. Scenario analysis was conducted for the intention-to-treat population and the favorable risk population. Furthermore, one-way sensitivity analysis and probabilistic sensitivity analysis were conducted for each population. RESULTS: In the base-case analysis, the QALYs of NIVO + IPI and SUN were 4.32 and 2.99, respectively. NIVO + IPI conferred 1.34 additional QALYs. Meanwhile, the total costs in the NIVO + IPI and SUN were $692 288 and $475 481, respectively. As a result, the ICER of NIVO + IPI compared with SUN was estimated to be $162 243 per QALY gained. The parameter that greatly affected the ICER was the utility weight of progression-free survival in NIVO + IPI. CONCLUSIONS: NIVO + IPI for advanced renal cell carcinoma seems to be not cost-effective compared with the SUN in the Japanese healthcare system.

Cost-effective analysis of transcatheter aortic valve replacement in patients with severe symptomatic aortic stenosis: A prospective multicenter study.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) for severe symptomatic aortic stenosis (AS) does not benefit all patients. We performed a prospective multicenter study to investigate the cost-effectiveness of TAVR in a Japanese cohort. METHODS AND RESULTS: We prospectively enrolled 110 symptomatic patients with severe AS who underwent TAVR from five institutions. The quality of life measurement (QOL) was performed for each patient before and at 6 months after TAVR. Patients without an improvement in QOL at 6 months after TAVR were defined as non-responders. Pre-TAVR higher QOL, higher clinical frailty scale predicted the non-responders. Three models, 1) conservative treatment for all patients strategy, 2) TAVR for all patients strategy, and 3) TAVR for a selected patient strategy who is expected to be a responder, were simulated. Lifetime cost-effectiveness was estimated using incremental cost-effectiveness ratio (ICER) and cost per quality-adjusted life-year (QALY) gained. In comparison to conservative therapy for all patients, ICER was estimated to be 5,765,800 yen/QALY for TAVR for all patients and 2,342,175 yen/QALY for TAVR for selected patient strategy patients, which is less than the commonly accepted ICER threshold of 5,000,000 yen/QALY. CONCLUSIONS: TAVR for selected patient strategy model is more cost-effective than TAVR for all patient strategy without reducing QOL in the Japanese healthcare system. TAVR for selected patient strategy has potential benefit for optimizing the TAVR treatment in patients with high frailty and may direct our resources toward beneficial interventions.

Cost-effectiveness analysis of nivolumab plus chemotherapy vs chemotherapy for patients with unresectable advanced or metastatic HER2-negative gastric or gastroesophageal junction or esophageal adenocarcinoma in Japan.

BACKGROUND: This study aimed to evaluate the cost-effectiveness of nivolumab plus chemotherapy (NIVO + Chemo) compared with chemotherapy monotherapy (Chemo) for patients with advanced or metastatic HER2-negative gastric or gastroesophageal junction or esophageal adenocarcinoma (GC/GEJC/EAC) in Japan from the perspective of healthcare payer. METHODS: A partitioned survival analysis model was developed to predict costs and quality-adjusted life years (QALYs) for NIVO + Chemo and Chemo. The time horizon of the model was set to 38 years. An annual discount rate of 2% for both costs and QALYs was applied. Data on overall survival and progression-free survival were derived from the CheckMate649 trial. Cost parameters were estimated from a Japanese medical claims database. The incremental cost-effectiveness ratio (ICER) of NIVO + Chemo compared with Chemo was estimated. A subgroup analysis on the level of PD-L1 CPS expression was conducted. In addition, sensitivity analysis was performed to assess the uncertainty in the parameter settings. RESULTS: The incremental cost and QALY of NIVO + Chemo compared with Chemo were USD99,416 and 0.30 QALY, respectively. The ICER of NIVO + Chemo was estimated to be USD327,161 per QALY gained. The results of the subgroup analysis showed that ICER was USD247,403/QALY and USD302,183/QALY for PD-L1 CPS ≧ 5 and ≧ 1, respectively. Sensitivity analyses showed a relatively robust result that the ICER remained higher than the Japanese cancer threshold of USD75,000-150,000/QALY. CONCLUSIONS: Applying the Japanese cancer threshold of USD75,000-150,000/QALY, NIVO + Chemo was not cost-effective for patients with advanced or metastatic HER2-negative GC/GEJC/EAC in Japan from the perspective of healthcare payer.

Cost-Effectiveness Analysis of Universal Screening for Biliary Atresia in Japan.

OBJECTIVE: To evaluate the cost-effectiveness of universal newborn screening using stool color card or direct bilirubin (DB) testing when comparing with no screening for biliary atresia in Japanese setting. STUDY DESIGN: A decision analytic Markov microsimulation model was developed to evaluate the universal screening for biliary atresia. Our screening strategies included stool color card, DB, or no screening. The outcomes of all newborns undergoing 3 strategies were simulated to analyze event-free life-years defined as liver transplant-free survival, costs, and incremental cost-effectiveness ratio (ICER) over a 25-year period with an annual discount rate of 2% applied for both costs and outcomes. A 1-way sensitivity analysis was performed to assess the uncertainty. RESULTS: There were 941 000 newborn infants in our cohort and 114 cases of biliary atresia. The base case analysis showed that the stool color card strategy was $14 927 337 higher than no screening with an increase in 44 more event-free life-years gained, resulting in an ICER of $339 258 per event-free life-year gained. The DB screening strategy compared with stool color card was $138 994 060 higher with an increase in 271 more event-free life-years gained and an ICER of $512 893 per event-free life-year gained. The DB screening strategy compared with no screening resulted in an ICER of $488 639 per event-free life-year gained. The DB screening resulted in 16 fewer liver transplants than stool color card and stool color card had 2 fewer liver transplants than no screening. CONCLUSIONS: Universal screening for biliary atresia could be cost-effective depending on the willingness to pay thresholds for health benefits.

Clinical impact of cardiac magnetic resonance in patients with suspected coronary artery disease associated with chronic kidney disease (AQUAMARINE-CKD study): study protocol for a randomized controlled trial.

BACKGROUND: Although screening for coronary artery disease (CAD) using computed tomography coronary angiography in patients with stable chest pain has been reported to be beneficial, patients with chronic kidney disease (CKD) might have limited benefit due to complications of contrast agent nephropathy and decreased diagnostic accuracy as a result of coronary artery calcifications. Cardiac magnetic resonance (CMR) has emerged as a novel imaging modality for detecting coronary stenosis and high-risk coronary plaques without contrast media that is not affected by coronary artery calcification. However, the clinical use of this technology has not been robustly evaluated. METHODS: AQUAMARINE-CKD is an open parallel-group prospective multicenter randomized controlled trial of 524 patients with CKD at high risk for CAD estimated based on risk factor categories for a Japanese urban population (Suita score) recruited from 6 institutions. Participants will be randomized 1:1 to receive a CMR examination that includes non-contrast T1-weighted imaging and coronary magnetic angiography (CMR group) or standard examinations that include stress myocardial scintigraphy (control group). Randomization will be conducted using a web-based system. The primary outcome is a composite of cardiovascular events at 1 year after study examinations: all-cause death, death from CAD, nonfatal myocardial infarction, nonfatal ischemic stroke, and ischemia-driven unplanned coronary intervention (percutaneous coronary intervention or coronary bypass surgery). DISCUSSION: If the combination of T1-weighted imaging and coronary magnetic angiography contributes to the risk assessment of CAD in patients with CKD, this study will have major clinical implications for the management of patients with CKD at high risk for CAD. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) 1,052,210,075. Registered on September 10, 2021.

Cost-Effectiveness of First-Line Nivolumab Plus Ipilimumab Combination Therapy in Advanced Non-Small-Cell Lung Cancer in Japan.

BACKGROUND AND OBJECTIVE: In Japan, indications for nivolumab have been expanded to include the combination therapy with ipilimumab in various cancers. This study aimed to evaluate the cost-effectiveness of combination therapy of nivolumab plus ipilimumab (NIV + IPI) for patients with advanced non-small-cell lung cancer (NSCLC), comparing it with platinum-doublet chemotherapy in Japanese settings. METHODS: A partitioned survival model was developed to predict costs and quality-adjusted life-years (QALYs) in a NIV + IPI arm and a chemotherapy arm. Data on overall survival and progression-free survival were derived from the CheckMate 227 trial. Cost estimates were based on a Japanese healthcare system perspective using real-world data from the JMDC claims database. Utilities were derived from published sources outside Japan. The incremental cost-effectiveness ratio (ICER) of NIV + IPI therapy compared with chemotherapy was estimated. A scenario analysis on the level of programmed death-ligand 1 (PD-L1) expression was conducted. In addition, sensitivity analyses were performed to assess the uncertainty in parameter settings. RESULTS: Compared with chemotherapy, NIV + IPI therapy incurred an additional cost of USD102,623 and conferred an additional 1.007 QALY, which resulted in an ICER of USD101,950/QALY gained. Contrary to prior expectations, the ICER of patients with a PD-L1 expression level ≥ 1% was higher than that of patients with a PD-L1 expression level < 1% (USD145,868/QALY and USD127,737/QALY, respectively). Sensitivity analyses showed a relatively robust result with the ICERs remaining higher than a Japanese price adjustment threshold of USD75,000/QALY with a few exceptions. CONCLUSIONS: The combination of NIV + IPI as first-line therapy would not be cost effective under a willingness-to-pay threshold of USD75,000/QALY from the perspective of the Japanese healthcare system.

Parathyroidectomy vs Cinacalcet Among Patients Undergoing Hemodialysis.

CONTEXT: Parathyroidectomy (PTx) and cinacalcet are both effective treatments for secondary hyperparathyroidism in hemodialysis patients, but limited data exist comparing the long-term outcomes of these interventions. OBJECTIVE: We aimed to compare the risk of mortality among hemodialysis patients who underwent PTx and those who started treatment with cinacalcet. METHODS: In this prospective cohort study, comprising patients from the Japanese Society for Dialysis Therapy Renal Data Registry, patients who had intact parathyroid hormone (PTH) levels ≥ 300 pg/mL in late 2007 and underwent PTx or started treatment with cinacalcet in 2008 to 2009 were matched by propensity score at 1:3. PTx and cinacalcet were compared for all-cause mortality within 6 years. RESULTS: Among eligible patients, 894 patients who underwent PTx were matched with 2682 patients who started treatment with cinacalcet. The median baseline intact PTH levels were 588 pg/mL and 566 pg/mL in the PTx and cinacalcet groups, respectively. PTx resulted in greater reductions in intact PTH, calcium, and phosphorus levels compared with cinacalcet. During the 6-year follow-up period, 201 patients (22.5%) in the PTx group and 736 patients (27.4%) in the cinacalcet group died. PTx was associated with a lower risk of mortality compared with cinacalcet (hazard ratio, 0.78 [95% CI, 0.67-0.91]; P = 0.002). This association was more pronounced in patients with intact PTH levels ≥ 500 pg/mL and in patients with serum calcium levels ≥ 10.0 mg/dL (both P for interaction < 0.001). CONCLUSION: PTx compared with cinacalcet is associated with a lower risk of mortality, particularly among patients with severe secondary hyperparathyroidism.

ChGn-2 Plays a Cardioprotective Role in Heart Failure Caused by Acute Pressure Overload.

Background Cardiac extracellular matrix is critically involved in cardiac homeostasis, and accumulation of chondroitin sulfate glycosaminoglycans (CS-GAGs) was previously shown to exacerbate heart failure by augmenting inflammation and fibrosis at the chronic phase. However, the mechanism by which CS-GAGs affect cardiac functions remains unclear, especially at the acute phase. Methods and Results We explored a role of CS-GAG in heart failure using mice with target deletion of ChGn-2 (chondroitin sulfate N-acetylgalactosaminyltransferase-2) that elongates CS chains of glycosaminoglycans. Heart failure was induced by transverse aortic constriction in mice. The role of CS-GAG derived from cardiac fibroblasts in cardiomyocyte death was analyzed. Cardiac fibroblasts were subjected to cyclic mechanical stretch that mimics increased workload in the heart. Significant CS-GAGs accumulation was detected in the heart of wild-type mice after transverse aortic constriction, which was substantially reduced in ChGn-2-/- mice. Loss of ChGn-2 deteriorated the cardiac dysfunction caused by pressure overload, accompanied by augmented cardiac hypertrophy and increased cardiomyocyte apoptosis. Cyclic mechanical stretch increased ChGn-2 expression and enhanced glycosaminoglycan production in cardiac fibroblasts. Conditioned medium derived from the stretched cardiac fibroblasts showed cardioprotective effects, which was abolished by CS-GAGs degradation. We found that CS-GAGs elicits cardioprotective effects via dual pathway; direct pathway through interaction with CD44, and indirect pathway through binding to and activating insulin-like growth factor-1. Conclusions Our data revealed the cardioprotective effects of CS-GAGs; therefore, CS-GAGs may play biphasic role in the development of heart failure; cardioprotective role at acute phase despite its possible unfavorable role in the advanced phase.

Direct health care cost of treatment and medication of biliary atresia patients using the National Database of Health Insurance Claims and Specific Health Checkups.

BACKGROUND: Treatment of biliary atresia (BA), which typically requires an initial surgical intervention called the Kasai procedure (KP) and possible liver transplant (LT) afterwards, is quite resource-intensive and would affect patients and families for a lifetime; yet a comprehensive view of the economic burden has not been reported. We estimated direct health care costs from the public payer perspective using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. METHODS: Children newly diagnosed at ages 0 days to 4 years between April 2010 and September 2019 were identified. Costs of treatment were estimated for six phases of care: prediagnosis, KP and inpatient hospitalization, follow-up after KP, pre-transplant checkup, LT and inpatient hospitalization, and follow-up after LT. RESULTS: Mean total prediagnosis medical cost was $6847 (USD) and KP and inpatient hospitalization was $42,157 per year. Follow-up after KP was $15,499, and pre-transplant checkup after KP was $36,015 per year. Mean cost for LT and inpatient hospitalization was $105,334, and follow-up after liver transplant was $25,459 per year. CONCLUSIONS: Treatment of BA requires extensive medical resource consumption. The use of the comprehensive national database allowed us to estimate the costs which will be useful for health service planning and cost-effectiveness analysis.

Cost-Effectiveness of Nab-Paclitaxel and Gemcitabine Versus Gemcitabine Monotherapy for Patients with Unresectable Metastatic Pancreatic Cancer in Japan.

OBJECTIVES: The purpose of this study was to evaluate the cost-effectiveness of nab-paclitaxel and gemcitabine (GnP) compared with gemcitabine monotherapy (G) for patients with unresectable metastatic pancreatic cancer in Japan from the perspective of healthcare payer. METHODS: A partitioned survival analysis model was developed to predict costs and quality-adjusted life years (QALYs) for GnP and G. The time horizon of the model was set at 20 years. An annual discount rate of 2% for both costs and QALYs was applied. Data on overall survival and progression-free survival were derived from the Metastatic Pancreatic Adenocarcinoma Clinical Trial. Cost parameters were estimated from a Japanese medical claims database. The incremental cost-effectiveness ratio (ICER) of GnP compared with G was estimated. One-way sensitivity analysis was performed to assess the uncertainty in the parameter settings. In addition, scenario and probability sensitivity analyses were performed. RESULTS: The incremental cost and QALY of GnP compared with G were US$25 089 and 0.13 QALY, respectively. The ICER of GnP was estimated to be US$192 992 per QALY gained. Although the ICER was influenced by utility parameters and the survival curves, the ICERs remained higher than the willingness to pay (WTP) threshold of US$68 000 (JPY 7.5 million). The probability that GnP becomes cost-effective compared with G was estimated to be 29.2%. CONCLUSIONS: Applying the WTP threshold of US$68 000 per QALY, GnP was not cost-effective for patients with unresectable metastatic pancreatic cancer in Japan from the perspective of healthcare payer. Further research is needed to obtain utility data from Japanese patients with pancreatic cancer.

Proton beam therapy for children and adolescents and young adults (AYAs): JASTRO and JSPHO Guidelines.

Children and adolescents and young adults (AYAs) with cancer are often treated with a multidisciplinary approach. This includes use of radiotherapy, which is important for local control, but may also cause adverse events in the long term, including second cancer. The risks for limited growth and development, endocrine dysfunction, reduced fertility and second cancer in children and AYAs are reduced by proton beam therapy (PBT), which has a dose distribution that decreases irradiation of normal organs while still targeting the tumor. To define the outcomes and characteristics of PBT in cancer treatment in pediatric and AYA patients, this document was developed by the Japanese Society for Radiation Oncology (JASTRO) and the Japanese Society of Pediatric Hematology/Oncology (JSPHO).

Cost-effectiveness analysis for HbA1c test intervals to screen patients with type 2 diabetes based on risk stratification.

BACKGROUND: The best HbA1c test interval strategy for detecting new type 2 diabetes mellitus (T2DM) cases in healthy individuals should be determined with consideration of HbA1c test characteristics, risk stratification towards T2DM and cost effectiveness. METHODS: State transition models were constructed to investigate the optimal screening interval for new cases of T2DM among each age- and BMI-stratified health individuals. Age was stratified into 30-44-, 45-59-, and 60-74-year-old age groups, and BMI was also stratified into underweight, normal, overweight and obesity. In each model, different HbA1c test intervals were evaluated with respect to the incremental cost-effectiveness ratio (ICER) and costs per quality-adjusted life year (QALY). Annual intervals (Japanese current strategy), every 3 years (recommendations in US and UK) and intervals which are tailored to each risk stratification group were compared. All model parameters, including costs for screening and treatment, rates for complications and mortality and utilities, were taken from published studies. The willingness-to-pay threshold in the cost-effectiveness analysis was set to US $50,000/QALY. RESULTS: The HbA1c test interval for detecting T2DM in healthy individuals varies by age and BMI. Three-year intervals were the most cost effective in obesity at all ages-30-44: $15,034/QALY, 45-59: $11,849/QALY, 60-74: $8685/QALY-compared with the other two interval strategies. The three-year interval was also the most cost effective in the 60-74-year-old age groups-underweight: $11,377/QALY, normal: $18,123/QALY, overweight: $12,537/QALY-and in the overweight 45-59-year-old group; $18,918/QALY. In other groups, the screening interval for detecting T2DM was found to be longer than 3 years, as previously reported. Annual screenings were dominated in many groups with low BMI and in younger age groups. Based on the probability distribution of the ICER, results were consistent among any groups. CONCLUSIONS: The three-year screening interval was optimal among elderly at all ages, the obesity at all ages and the overweight in 45-59-year-old group. For those sin the low-BMI and younger age groups, the optimal HbA1c test interval could be longer than 3 years. Annual screening to detect T2DM was not cost effective and should not be applied in any population.

Economic Evaluation of First-Line Pertuzumab Therapy in Patients with HER2-Positive Metastatic Breast Cancer in Japan.

OBJECTIVE: The purpose of this analysis was to evaluate the cost effectiveness of the combination of pertuzumab, trastuzumab, and docetaxel (PTD) for the treatment of patients with human epidermal growth factor receptor-2 (HER2)-positive breast cancer in Japan. METHODS: A partitioned survival analysis model was developed to predict costs and quality-adjusted life-years (QALYs) in a PTD arm and a trastuzumab plus docetaxel (TD) arm. Direct medical costs were considered from the perspective of the Japanese healthcare system. The time horizon of the model was set to 20 years. Data on overall survival and progression-free survival were derived from the CLEOPATRA trial. Cost parameters were estimated using a real-world claims database. Utilities were derived from published sources outside Japan. The incremental cost-effectiveness ratio (ICER) of PTD therapy compared with TD therapy was estimated. Sensitivity analysis was conducted to assess the uncertainty in parameter settings. RESULTS: Compared with TD therapy, PTD therapy incurred an additional cost of $US174,479 and conferred an additional 0.949 QALYs. This resulted in an ICER of $US183,901 per QALY gained. Utility weights for progression-free survival and progressed disease had a relatively large impact on the base-case result, but the ICERs remained higher than $US75,000 per QALY over the full range of model parameters. Based on a probabilistic sensitivity analysis, the probability that PTD is cost effective was estimated to be 3.3%. CONCLUSIONS: Applying a willingness-to-pay threshold of $US75,000 per QALY, PTD therapy as first-line therapy would not be cost effective. Further research is required on utilities and clinical benefits for Japanese patients with breast cancer.

Cost-effectiveness of a hybrid emergency room system for severe trauma: a health technology assessment from the perspective of the third-party payer in Japan.

BACKGROUND: Hybrid emergency room (ER) systems, consisting of an angiography-computed tomography (CT) machine in a trauma resuscitation room, are reported to be effective for reducing death from exsanguination in trauma patients. We aimed to investigate the cost-effectiveness of a hybrid ER system in severe trauma patients without severe traumatic brain injury (TBI). METHODS: We conducted a cost-utility analysis comparing the hybrid ER system to the conventional ER system from the perspective of the third-party healthcare payer in Japan. A short-term decision tree and a long-term Markov model using a lifetime time horizon were constructed to estimate quality-adjusted life years (QALYs) and associated lifetime healthcare costs. Short-term mortality and healthcare costs were derived from medical records and claims data in a tertiary care hospital with a hybrid ER. Long-term mortality and utilities were extrapolated from the literature. The willingness-to-pay threshold was set at $47,619 per QALY gained and the discount rate was 2%. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: The hybrid ER system was associated with a gain of 1.03 QALYs and an increment of $33,591 lifetime costs compared to the conventional ER system, resulting in an ICER of $32,522 per QALY gained. The ICER was lower than the willingness-to-pay threshold if the odds ratio of 28-day mortality was < 0.66. Probabilistic sensitivity analysis indicated that the hybrid ER system was cost-effective with a 79.3% probability. CONCLUSION: The present study suggested that the hybrid ER system is a likely cost-effective strategy for treating severe trauma patients without severe TBI.

Factors influencing the prescribed dose of opioid analgesics in cancer patients.

The dose of opioids prescribed for cancer pain does not always correlate with the actual pain severity. However, there is little evidence to explain this observation. In the present study, we sought to determine factors that influence the dose of opioid analgesics. A total of 227 patients who were administered opioids between August 2012 and May 2016 and later expired within the Department of Palliative Care at Ashiya Municipal Hospital were included, and the following variables were examined: age, sex, type of cancer, Verbal Rating Scale before and after the administration of the maximum pre-scribed dose of opioids, type of opioids and route of administration, blood test results, pain severity, and use of adju-vants. Data were analyzed using step-wise multiple linear regression. Median of the maximum prescribed dose of opioids, expressed in oral morphine equivalent, was 68.6, 60.0, and 39.2 mg for patients aged <65, 65-74, and ≥75 years, respectively. Step-wise multiple linear regression analysis further demonstrated that an increase in age by 1 year decreased the maximum prescribed dose of opioids by 0.98-fold (p = 0.006). Other factors that influenced the maximum prescribed dose of opioids included the use of analgesic adjuvants (1.91-fold, p = 0.001), oral administration (0.54-fold, p = 0.016), and elevated level of bilirubin (0.95-fold by 0.1 mg/dL increase, p = 0.013). Opioids examined in the study are metabolized in the liver by cytochromes P450 or by glucuronidation. Thus, if reduced drug metabolism causes the reduction in the maximum prescribed dose of opioids, liver function may contribute to this effect. Based on our findings that old age is associated with a lower prescribed dose of opioids, future studies should examine additional variables included in laboratory tests in more detail and measure hepatic blood flow to determine the cause of this as-sociation.

Differences in healthcare expenditure estimates according to statistical approach: A nationwide claims database study on patients with hepatocellular carcinoma.

AIM: Disease-associated healthcare expenditures are generally calculated using matched comparisons or regression-based analyses, but little is known about their differences in estimates. This aim of this study was to compare the differences between disease-associated healthcare expenditures estimated using these 2 methods. METHODS: In this retrospective cohort study, a matched comparison was first conducted by matching cases with controls using sex, age, and comorbidities to estimate disease-associated expenditures. The cases were then used in a fixed-effects analysis that compared expenditures before and after disease occurrence. The subjects were adults (≥20 years) with primary hepatocellular carcinoma (HCC) who underwent treatment (including surgical resection, locoregional therapy, transcatheter arterial chemoembolization, and transarterial embolization) at a Japanese hospital between April 2010 and March 2018. We calculated the total healthcare expenditures per patient per month according to treatment and disease phase (initial, continuing, and terminal). RESULTS: There were 14,923 cases in the initial/continuing phases and 15,968 cases in the terminal phase. In the initial/continuing phases, 3,552 patients underwent surgical resection only, with HCC-associated expenditures of $5,555 according to the matched comparison and $5,889 according to the fixed-effects analysis (proportional difference: 94.3%). The initial phase expenditures were approximately 9% higher in the fixed-effects analysis, whereas the continuing phase expenditures were approximately 7% higher in the matched comparison. The expenditures in the terminal phase were 93.1% higher in the fixed-effects analysis. CONCLUSIONS: The 2 methods produced similar estimates of HCC-associated healthcare expenditures in the initial/continuing phases. However, terminal phase expenditures were substantially different between the methods.

The relationship between preference-based health-related quality of life and lifestyle behavior: a cross-sectional study on a community sample of adults who had undergone a health check-up.

BACKGROUND: Preference-based Health-Related Quality of Life (HRQL) is one of the most important indicators for calculating QALY (Quality-Adjusted Life Years) in a cost-effectiveness analysis. This study aimed to collect data on healthy individuals' HRQL based on the preferences of Japanese people who had undergone a comprehensive health check-up, and to examine the influence of relevant factors, such as blood biochemical data and lifestyle behavior. METHODS: We conducted a cross-sectional study targeting people who had undergone a comprehensive health check-up in 2015. Participants were asked to respond to a medical interview sheet. We then examined the utility value, as well as lifestyle habits such as alcohol intake, smoking, and exercise. HRQL was examined using EQ-5D-5L. Using a multiple regression analysis, we examined the influence of related factors, such as lifestyle and biochemical test data. RESULTS: We collected 2037 responses (mean age = 54.98 years; 55.0% female). The average preference-based health-related HRQL was 0.936 ± 0.087. A total of 1167 people (57.2%) responded that they were completely healthy. The biochemical test data that were recognized to correlate with HRQL were hemoglobin, total cholesterol, creatinine, all of which were weak (r = - 0.045-0.113). The results of multiple regression analysis showed that significant facts were: being female, age (≧70 year-old), drinking alcohol (sometimes), activity (very often), and lack of sleep. CONCLUSIONS: The HRQL of participants who had undergone a comprehensive health check-up was generally high, and only declined for those over 70 years of age. It is suggested that preference-based HRQL is related to physical activity, and that decrease of activity and lack of sleep leads to a decrease in HRQL.

Present developments in reaching an international consensus for a model-based approach to particle beam therapy.

Particle beam therapy (PBT), including proton and carbon ion therapy, is an emerging innovative treatment for cancer patients. Due to the high cost of and limited access to treatment, meticulous selection of patients who would benefit most from PBT, when compared with standard X-ray therapy (XRT), is necessary. Due to the cost and labor involved in randomized controlled trials, the model-based approach (MBA) is used as an alternative means of establishing scientific evidence in medicine, and it can be improved continuously. Good databases and reasonable models are crucial for the reliability of this approach. The tumor control probability and normal tissue complication probability models are good illustrations of the advantages of PBT, but pre-existing NTCP models have been derived from historical patient treatments from the XRT era. This highlights the necessity of prospectively analyzing specific treatment-related toxicities in order to develop PBT-compatible models. An international consensus has been reached at the Global Institution for Collaborative Research and Education (GI-CoRE) joint symposium, concluding that a systematically developed model is required for model accuracy and performance. Six important steps that need to be observed in these considerations include patient selection, treatment planning, beam delivery, dose verification, response assessment, and data analysis. Advanced technologies in radiotherapy and computer science can be integrated to improve the efficacy of a treatment. Model validation and appropriately defined thresholds in a cost-effectiveness centered manner, together with quality assurance in the treatment planning, have to be achieved prior to clinical implementation.

Enhancing Study Motivation and Efficacy among First-year Students Using Minute Papers in the Interdisciplinary Subject of Yakugaku Nyumon.

Active learning in higher education is important for learning efficacy and motivation. Accordingly, lectures that integrate strategies toward active learning, such as minute papers, debates, and collaborative learning, have become widely adopted. Minute papers facilitate communication among both teachers and students, and can be used as a tool for reviewing lectures. In the present study, we examined the effect of using minute papers on learning efficacy and motivation. To enhance the curriculum of the interdisciplinary course Yakugaku Nyumon, which consists of an omnibus lecture series and problem-based learning, minute papers with exercises were provided to applicants. In a follow-up questionnaire, students who used minute papers (S-USE) responded that they had a better understanding of the relationships, ranging from basic to clinical subject matter, than students who did not use such papers (S-NON). Using the Attention, Relevance, Confidence, and Satisfaction (ARCS) model questionnaire to measure study motivation, S-USE scored higher for some questionnaires than S-NON. This finding indicates that minute papers promoted learning motivation among students taking the Yakugaku Nyumon course. In regular examinations, the average score of S-USE was also statistically higher than that of S-NON. These results demonstrate that minute papers possibly encouraged students to actively review the lectures, thereby increasing both learning efficacy and motivation. This study shows that through promoting active, self-learning, minute papers are suitable for improving curricular strategies in subjects that rely on passive learning methods.

[Cost-effectiveness of implementing Osteoporosis Liaison Service program.]

Facing with swelling medical expenses, bringing a viewpoint of cost-effectiveness to disease management of osteoporosis has become important. Previous economic evaluations from the UK and the USA have reported that implementing a Fracture Liaison Service program reduces refracture rates and results in healthcare cost-savings. In recent years, a model-based cost-effectiveness analysis has been performed in Japan and reported Secondary fracture prevention by Osteoporosis Liaison Service program is cost-effective in Japanese women with osteoporosis who have suffered a hip fracture. In addition, secondary fracture prevention is less expensive than no therapy in high-risk patients with multiple risk factors.