Comparison of Treatment Goals between Users of Biological and Non-Biological Therapies for Treatment of Psoriasis in Japan.

BACKGROUND: Previously, our cross-sectional observational study in Japan revealed high (68%) discordance within treatment goals between psoriasis patients and their physicians. OBJECTIVE: This secondary analysis aimed to determine whether patient and physician users of biologics have higher treatment goals than users of non-biologics. METHODS: A survey for both patients and physicians on background characteristics, disease severity, treatment goals, treatment satisfaction, and health-related quality of life was conducted at 54 sites. Association between treatment goals and biologic/non-biologic users was assessed using ordinal logistic regression models. RESULTS: In total, 449 patient-physician pairs agreed to participate; 425 completed the survey and were analyzed. More biologic users than non-biologic users reported complete clearance (Psoriasis Area and Severity Index 100) as a treatment goal (patient-reported: 23.6% vs. 16.1%; physician-reported: 26.9% vs. 2.2%). Biologic users were significantly associated with higher treatment goals than non-biologic users (patient-reported: 1.8 (1.15-2.87) (odds ratio (9 5% CI)), p = 0.01; physician-reported: 11.0 (5.72-21.01), p < 0.01). Among biologic users, higher treatment goals were associated with higher treatment satisfaction (patient- and physician-rated); lower treatment goals were associated with back lesions and increasing patient age (patient-rated) and higher disease severity (physician-rated). CONCLUSION: Use of biologics among patients with psoriasis was associated with higher treatment goals. Further use of biologics contributed to treatment satisfaction. Appropriate treatment goals that are shared among patients and their physicians may improve treatment outcomes.

The Use of patient Reported Outcome Measures for Rheumatoid Arthritis in Japan: A Systematic Literature Review.

BACKGROUND: Patient-reported outcomes (PRO) obtained through routine medical care may identify patients' day-to-day burden and help tackle the disease from the patients' perspective. However, there is a paucity of information regarding the availability of PRO data and PRO tools for rheumatoid arthritis (RA) in Japan. OBJECTIVE: We reviewed the literature on PRO data availability and to identify PRO measures implemented in Japan for RA patients. METHOD: We conducted a systematic literature review using ICHUSHI and the PubMed databases on PRO measures for RA published from January 2011 to August 2015 in Japan. RESULTS: After removing duplicates, 2423 manuscripts were found. From these, 100 manuscripts were included for review and analysis. We found 29 PRO tools that were used to assess various domains of health such as general well-being, pain, functionality, and fatigue. More than 90% of the studies utilized PRO tools for research purpose. Only one study reported PRO tool implementation in the routine medical care. CONCLUSION: The importance of PROs is recognized in Japan. PRO tools varied significantly and were mostly used for research purposes, while reports on the use of PRO measures in routine medical care were limited. Despite the awareness of PROs in the research community, unmet needs remain among RA patients in Japan. Further work is needed to investigate ways in which PROs can better reflect these unmet needs and be utilized in routine medical care.

Estimating the cost-effectiveness of daclatasvir plus asunaprevir in difficult to treat Japanese patients chronically infected with hepatitis C genotype 1b.

AIM: Standard of care for chronic hepatitis C in Japan is currently a pegylated interferon (IFN)-α + ribavirin (PR)-based regimen, notably associated with efficacy and tolerability issues. The advent of novel direct-acting antivirals (DAA) has provided more efficacious and better tolerated treatments. This study investigated the cost-effectiveness of the daclatasvir + asunaprevir (DCV + ASV) DAA regimen in patients infected with hepatitis C virus (HCV) genotype 1b who had previously not responded to or were ineligible for IFN-containing regimens. METHODS: A cost-utility analysis using an established Markov model compared DCV + ASV with simeprevir + PR (SMV + PR), telaprevir + PR (TVR + PR) and no treatment using Japanese-specific model inputs, with costs and utility values discounted at 2%. A cohort of patients was simulated until death and predicted quality-adjusted life-years (QALY) and costs were estimated. A subgroup analysis of patients with no DCV resistance was conducted. RESULTS: In all scenarios, DCV + ASV was predicted to be dominant over the comparator; namely, DCV + ASV was associated with increased QALY gains and decreased cost. In patients treated during the chronic hepatitis C stage, cost reductions were ¥1 057 288-2 619 206, and in patients treated during the compensated cirrhosis (CC) stage, reductions were ¥1 032 224-2 531 930. QALY gains were 0.749-2.609 and 0.874-3.043, respectively. Results improved when considering the subgroup of patients without DCV resistance. CONCLUSION: Cost-effectiveness conclusions are similar for patients treated in the chronic hepatitis C and CC disease stages, with DCV + ASV expected to be cost-saving versus standard of care in Japan for patients with HCV genotype 1b patients who have failed prior therapy or are IFN-ineligible/intolerant.

Cost-effectiveness Analysis of Apixaban against Warfarin for Stroke Prevention in Patients with Nonvalvular Atrial Fibrillation in Japan.

PURPOSE: The aim of this study was to evaluate the cost-effectiveness of apixaban compared with to warfarin, current standard of care, for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) in Japan. METHODS: A previously published lifetime Markov model was adapted to evaluate the cost-effectiveness of apixaban compared with warfarin in patients with NVAF in Japan. In the same model, the costs associated with each clinical event and background mortality were replaced with Japanese data. Whenever available, some of the utility parameters were derived from Japanese published literature. Lifetime horizon was selected to evaluate the value of the treatment benefit (stroke prevention) against potential risks (such as major bleedings) among patients with NVAF. Direct medical cost, long-term care cost, and quality-adjusted life years (QALYs) were calculated from the payers' perspective. FINDINGS: Compared with warfarin, treatment with apixaban was estimated to increase life expectancy by 0.231 year or 0.240 QALYs while treatment cost increased by ¥511,692 (US $5117 at an exchange rate of US $1 = ¥100). The incremental cost-effectiveness ratio was ¥2,135,743 per QALY (US $21,357 per QALY). On the basis of the results of the probabilistic sensitivity analysis, when the willingness-to-pay threshold was set at approximately ≥¥2,250,000 (US $22,500) per QALY, the probability of apixaban being cost-effective was ≥50%. Assuming a willingness-to-pay threshold of ¥5,000,000 (US $50,000) and ¥6,700,000 (US $67,000) in Japan, the probability of apixaban being cost-effective was 85% and 91%, respectively. CONCLUSION: Although most participants in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial used for the efficacy data of apixaban in the model were non-Japanese patients, the impact of the limitations on our results was considered small, and our results were deemed robust because of the additional effect in Japanese patients compared with that in the global population according to the subanalysis of Japanese patients in the trial. Therefore, based on an adaptation of a published Markov model, apixaban is a cost-effective alternative to warfarin in Japan for stroke prevention among patients with NVAF.

Induction of autophagy supports the bioenergetic demands of quiescent muscle stem cell activation.

The exit of a stem cell out of quiescence into an activated state is characterized by major metabolic changes associated with increased biosynthesis of proteins and macromolecules. The regulation of this transition is poorly understood. Using muscle stem cells, or satellite cells (SCs), we found that autophagy, which catabolizes intracellular contents to maintain proteostasis and to produce energy during nutrient deprivation, was induced during SC activation. Inhibition of autophagy suppressed the increase in ATP levels and delayed SC activation, both of which could be partially rescued by exogenous pyruvate as an energy source, suggesting that autophagy may provide nutrients necessary to meet bioenergetic demands during this critical transition from quiescence to activation. We found that SIRT1, a known nutrient sensor, regulates autophagic flux in SC progeny. A deficiency of SIRT1 led to a delay in SC activation that could also be partially rescued by exogenous pyruvate. These studies suggest that autophagy, regulated by SIRT1, may play an important role during SC activation to meet the high bioenergetic demands of the activation process.

Estimating the Long-Term Clinical and Economic Outcomes of Daclatasvir Plus Asunaprevir in Difficult-to-Treat Japanese Patients Chronically Infected with Hepatitis C Genotype 1b.

OBJECTIVES: Japan has one of the highest endemic rates of hepatitis C virus (HCV) infection. Treatments in Japan are currently limited to interferon-alfa-based regimens, which are associated with tolerability and efficacy issues. A novel regimen combining two oral HCV therapies, daclatasvir and asunaprevir (DCV + ASV), has shown favorable results in Japanese patients with chronic genotype 1b HCV infection. Comparisons of clinical and economic outcomes associated with DCV + ASV treatment and current standards of care were investigated. METHODS: The MOdelling the NAtural histoRy and Cost-effectiveness of Hepatitis cost-effectiveness model projected outcomes in 1000 patients aged 70 years with either chronic hepatitis C or compensated cirrhosis over a lifetime simulation. Japanese-specific disease transition rates were used, and discounting was applied annually at a rate of 2%. Efficacy data for DCV + ASV and telaprevir triple therapy (telaprevir + pegylated interferon-alfa + ribavirin [TVR + pegIFN-α/RBV]) were obtained from a Japanese subgroup analysis found within a global meta-analysis: sustained virological response rates of 74%, 85%, and 87% were reported for null responders (NRs), partial responders (PRs), and interferon-alfa-ineligible/intolerant patients, respectively, treated with DCV + ASV, and rates of 42% and 59% were reported for NRs and PRs, respectively, treated with TVR + pegIFN-α/RBV. RESULTS: Initiating DCV + ASV treatment in patients in the chronic hepatitis C disease stage resulted in quality-adjusted life-year gains of 0.96 and 0.77 over TVR + pegIFN-α/RBV for NRs and PRs, respectively, and a gain of 2.61 in interferon-alfa-ineligible/intolerant patients over no treatment. Similarly, quality-adjusted life-year gains of 1.11, 0.90, and 3.05 were observed when initiating treatment in patients in the compensated cirrhosis stage. Cumulative lifetime events of decompensated cirrhosis, hepatocellular carcinoma, and liver-related mortality were reduced by up to 66, 115, and 128, respectively, with DCV + ASV treatment. CONCLUSIONS: There is a lack of successful therapies for patients with HCV who have previously failed to achieve sustained virological response or are ineligible for interferon-alfa-based therapies. Results demonstrate that the provision of an alternative, interferon-alfa-free regimen, such as DCV + ASV, offers significant value in terms of avoiding life-threatening liver complications and increasing patients' quality of life.

The Patient-Related Burden of Pegylated-Interferon-α Therapy and Adverse Events among Patients with Viral Hepatitis C in Japan.

OBJECTIVES: Pegylated-interferon-α (IFN-α)-based therapies for viral hepatitis C (HCV) are effective, but they are associated with several adverse events (AEs). The primary objectives of this study were to quantify the burden of IFN-α-based treatment and to measure the prevalence and burden of IFN-α-related AEs in Japan. METHODS: A cross-sectional survey was administered online to patients with HCV in 2013. Patients who were currently taking IFN-α-based therapy (n = 188) were compared with patients who were taking a liver protectant but not IFN-α-based therapy (n = 180) and with patients who were untreated (n = 365) on measures of health-related quality of life (using the Hepatitis Quality of Life Questionnaire, version 2), work productivity, and health care resource use, controlling for sociodemographic characteristics and health history. Among patients taking IFN-α-based therapy, the prevalence and burden of AEs was examined on the same set of health outcomes as noted above along with treatment satisfaction and adherence. RESULTS: Compared with untreated patients, patients using IFN-α reported poorer health-related quality of life (physical component summary score, 50.13 vs. 52.04; mental component summary score, 44.12 vs. 47.97), more overall work impairment (32.73 vs. 25.64), more physician visits in the past 6 months (14.51 vs. 8.36), and an increased likelihood of an emergency room visit (odds ratio = 7.25) and hospitalization (odds ratio = 4.05) (all P < 0.05). The mean number of AEs was 6.05 for patients using IFN-α. All AEs were associated with poorer health outcomes (particularly the mental component summary score), and most were also associated with lower treatment satisfaction and medication adherence. CONCLUSIONS: A significant patient burden for IFN-α treatment itself and various AEs was observed. The results suggest that effective, non-IFN-α-based treatments may reduce the societal burden.

Characteristics of medical school graduates who underwent problem-based learning.

INTRODUCTION: In this study, we compared the choice of medical specialty and subspecialty interest among problem-based-learning (PBL) graduates and non-PBL graduates. MATERIALS AND METHODS: Questionnaires were mailed to a total of 1398 female doctors who graduated from Tokyo Women's Medical University (TWMU) between 1989 and 2003. The response rate was over 30%, giving 248 respondents who had undergone a PBL curriculum (PBL+) and 220 subjects who had not (PBL-). Current specialty of the graduates were compared between the PBL+ and PBL-, and also compared with the general Japanese female doctors (Control 1 and 2) of similar age groups. Respondents were analysed in terms of their interests in subspecialty medical care or general medical practise, which includes comprehensive medical care, primary care and basic medicine. Internal medicine doctors working in the university hospitals were compared with those working outside the university hospitals. Internal medicine doctors were also compared with specialists in ophthalmology, otolaryngology, dermatology and psychiatry. Subjects were compared by odds ratio (OR) to examine group difference in the field of interest. OR >2.0 was considered statistically significant. RESULTS: Most doctors in all groups chose internal medicine. More PBL+ internal medicine doctors showed interests in comprehensive medical care and primary care; more PBL+ internal medicine doctors working outside university hospitals showed interest in comprehensive medical care and primary care when compared with those who were working in the university hospitals. The PBL- graduates did not show such a characteristic. CONCLUSIONS: More PBL+ graduates who chose internal medicine showed interest in holistic medical practices such as primary care and community medicine and more PBL+ specialists showed sustained interest in their respective fields.

Facilitation of problem finding among first year medical school students undergoing problem-based learning.

BACKGROUND: Adaptation to problem-based learning (PBL) is a difficult process for high school graduates who are not used to self-directed learning, especially in the freshmen year of medical school. The difficulty includes finding problems from a given case. PURPOSE: Evaluate the effect of an intervention to facilitate case-based problem finding among medical school freshmen undergoing a PBL tutorial. METHODS: Medical school freshmen in 2000 (nonintervened group) and 2001 (intervened group) participated in the study. The intervened group received the modified problem-based program by (a) having briefings on the importance of problem finding, (b) encouragement by the tutors in problem finding, and (c) reinforcement using a self-assessment sheet. At the end of the year, the ability of students to extract problems from a short case was evaluated and compared with the nonintervened students. RESULTS: The intervened group extracted a significantly greater number of problems than the nonintervened group. When extracted problems were categorized, the intervened group was able to generate more questions in a greater number of specified categories. CONCLUSIONS: Interventions to foster problem finding significantly facilitated acquisition of problem extraction skills among young medical students.