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To estimate the medical costs related to Parkinson's disease (PD) by Hoehn and Yahr (HY) scale, we conducted a descriptive study by using a large-scale hospital based administrative claims database in Japan. Approximately 20,000 PD patients who had a diagnosis of PD with HY severity between April 2008 and December 2018 were included in the analysis. Estimated PD related outpatient costs, frequency of hospitalization, length of stay, and inpatient costs were increased with HY severity. Our estimates of the PD related medical costs are based on the large-scale claims database, despite limitations such as the reliability of HY severity in the claims data, could be used in future cost-effectiveness studies for treatment of PD.

Background and Aim Thrombocytopenia is a frequent hematological condition in chronic liver disease (CLD) patients increasing the risk of bleeding in patients undergoing invasive procedures. Without an alternative, clinical guidelines recommended the use of platelet transfusion (PT) prior to procedure to prevent this bleeding risk. Lusutrombopag (LUSU), an orally active, small‐molecule thrombopoietin receptor agonist, was developed as an alternative to PT. The objective of this study was to evaluate a cost‐effectiveness of LUSU as a potential alternative to PT in Japan. Methods A cost‐effectiveness analysis of LUSU relative to PT was conducted by a simulation model consisting of a decision tree combined to Markov model. Quality‐adjusted life years (QALYs) were used as an indicator of efficacy, and the analysis was conducted from the Japanese public healthcare payer's perspective. The time horizon of the analysis was 50 years (a lifetime) and the discount rate was set at 2%. Results LUSU gained 6.1803 QALYs with an expected lifetime costs of 2 380 219 JPY compared to PT with 6.1712 QALYs gained and expected lifetime costs of 2 382 908 JPY. Thus, LUSU was deemed dominant compared with PT. Based on probabilistic analyses, the chance of LUSU being dominant and the incremental cost‐effectiveness ratio being below 5 million JPY/QALY was estimated at 51.8% and 78.3%, respectively, demonstrating the robustness of the results. Conclusions LUSU was evaluated as an efficacious and cost‐saving treatment option for Japanese CLD patients with thrombocytopenia who required a planned invasive procedure compared with PT and economically should be considered as an alternative treatment., Thrombocytopenia is a frequent hematological condition in chronic liver disease (CLD) patients increasing the risk of bleeding in patients undergoing invasive procedures, and the use of platelet transfusion (PT) was recommended prior to procedure to prevent this bleeding risk. This study evaluated the cost‐effectiveness of lusutrombopag (LUSU) as a potential alternative to PT in Japan by using a simulation model consisting of a decision tree combined to Markov model. Compared with PT, LUSU was found to be an efficacious and cost‐saving treatment option for Japanese CLD patients with thrombocytopenia who required a planned invasive procedure.

The prevalence of primary axillary hyperhidrosis in Japan is 5.75% (males, 6.60%; females, 4.72%) in the population aged 5–64 years. No study on comprehensively evaluated direct medical costs, hygiene product costs, and productivity loss in axillary hyperhidrosis patients has been published in Japan. The aim of this study was to estimate the cost of illness for axillary hyperhidrosis in Japan by conducting a nationwide insurance claims database analysis and a cross‐sectional Web‐based survey. Among patients diagnosed with primary axillary hyperhidrosis at least once between November 2012 and October 2019, health insurance receipt data of 1447 patients were analyzed. A cross‐sectional Web‐based survey was conducted on 321 patients aged 16–59 years with axillary hyperhidrosis to calculate hygiene product costs and productivity loss using a Work Productivity and Activity Impairment questionnaire. Furthermore, nationwide estimation was performed for the hygiene product costs and productivity loss based on the number of patients estimated from the prevalence. The annual direct medical costs per axillary hyperhidrosis patient were ¥91 491 in 2016, ¥93 155 in 2017, and ¥75 036 in 2018. In all of these years, botulinum toxin type A injection accounted for approximately 90% of the total costs. The annual total cost of hygiene products per axillary hyperhidrosis patient was ¥9325. The overall work impairment (%) of working patients with axillary hyperhidrosis was 30.52%, and its monthly productivity loss was ¥120 593/patient. The activity impairment (%) of full‐time housewives with axillary hyperhidrosis was 49.05% and its monthly productivity loss was ¥176 368/patient. The annual hygiene product cost based on the nationwide estimation was ¥24.5 billion and the monthly productivity loss was ¥312 billion. The significant cost associated with axillary hyperhidrosis was clarified. If out‐of‐pocket expenses for treatments not covered by health insurance are included in the estimation, the cost will further increase.

Background We aimed to evaluate cost-effectiveness of enzalutamide in chemotherapy-naïve metastatic castration-resistant prostate cancer patients in Japan. Methods A Markov model was developed to capture time spent by patients in various health states: stable, progression and death. Abiraterone acetate and docetaxel were set as active comparators. Clinical outcomes were obtained from the PREVAIL, COU-AA-302 and TAX327 trials. Treatment sequence, concomitant drugs and therapies for adverse events were estimated from responses to a survey by 14 Japanese prostate cancer experts. The analytic perspective was public healthcare payer, with a 10-year time horizon. The incremental cost-effectiveness ratio was estimated from quality-adjusted life-years and Japanese public healthcare costs. Probabilistic sensitivity analysis was performed to assess the robustness of the findings. Results According to the survey, the most common treatment sequences were (i) enzalutamide → docetaxel → cabazitaxel (enzalutamide-first sequencing), (ii) abiraterone → enzalutamide → docetaxel (abiraterone-first sequencing) and (iii) docetaxel→ enzalutamide → cabazitaxel (docetaxel-first sequencing). In the base-case analysis, enzalutamide-first sequencing saved 1.74 million Japanese Yen versus abiraterone-first sequencing, with a 0.129 quality-adjusted life-year gain (dominant). Enzalutamide-first sequencing had a cost increase of 4.44 million Japanese Yen over docetaxel-first sequencing, with a 0.371 quality-adjusted life-years gain. The incremental cost-effectiveness ratio of enzalutamide-first sequencing versus docetaxel-first sequencing was estimated as 11.94 million Japanese Yen/quality-adjusted life-years. Probabilistic sensitivity analyses demonstrated that, compared with abiraterone-first sequencing, enzalutamide-first sequencing had an 87.4% probability of being dominant. Conclusions Results modeled herein suggest that the enzalutamide-first sequencing is more cost-effective than the abiraterone-first sequencing, but less cost-effective than docetaxel-first sequencing for chemotherapy-naïve patients with metastatic castration-resistant prostate cancer., As a result of a cost-effectiveness analysis, enzalutamide is suggested to be cost-saving versus abiraterone, but less cost-effective than docetaxel, for chemotherapy-naïve patients with metastatic castration-resistant prostate cancer in Japan.

Background The aim of this study was to evaluate the cardio-metabolic risk in schizophrenia patients treated by atypical antipsychotic drugs compared with that in those treated without atypical antipsychotic drugs using a nationwide insurance claims database and medical examination database in Japan. Methods Eligible patients were defined as those meeting the following two criteria: (i) A diagnosis of schizophrenia (ICD-10 code: F20) was made between 1 January 2005 and 31 December 2017, with data available for at least 6 months before the diagnosis was made (index month), and (ii) health check-up data were available within ±3 months of the index month. The primary endpoint was changes in cardio-metabolic risk based on the Suita score at 1 year, and the secondary endpoints were changes in medical examination data related to cardio-metabolic risk (total cholesterol [TC], triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, body mass index [BMI], and hemoglobin A1c) at 1 year. The primary endpoint was evaluated by multivariate analysis, with the cumulative chlorpromazine equivalent amount and the baseline Suita score added as covariates. Results One-hundred eighty five pairs of propensity score (PS)-matched patients were evaluated. Patients receiving atypical antipsychotic drugs exhibited a greater change in the Suita score and a risk of coronary heart disease based on the Suita score of 0.530 and 0.098%, respectively, than patients not receiving atypical antipsychotic drugs, but there was no significant difference (p = 0.412 and 0.610). The significant changes in TC and BMI were determined as 6.525 mg/dL and 0.380 kg/m2 greater, respectively, in patients treated with atypical antipsychotic drugs (p = 0.037 and 0.011). Conclusions There were no significant increases in changes in the Suita score at 1 year by treatment with atypical antipsychotic drugs compared with treatment without atypical antipsychotic drugs. However, the TC and BMI were significantly higher in patients treated with atypical antipsychotic drugs.

Yoshiteru Takekita,1 Sachie Inoue,2 Kenji Baba,3 Tadashi Nosaka3 1Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan; 2CRECON Medical Assessment Inc, Tokyo, Japan; 3Sumitomo Dainippon Pharma Co, Ltd, Tokyo, JapanCorrespondence: Yoshiteru TakekitaDepartment of Neuropsychiatry, Kansai Medical University, 10-15 Fumizono-Cho, Moriguchi, Osaka 570-8506, JapanTel +81-6-6992-1001Fax +81-6-6992-4846Email takekity@takii.kmu.ac.jpPurpose: The aim of this study was to examine whether there is a difference in the risk of rehospitalization when antipsychotics are classified into two groups treated using drugs with a higher or lower affinity to H1 or α 1 receptors than to D2 receptors (histamine H1 receptors, adrenaline α 1 receptors [HA] high- and HA low-affinity drug group, respectively) based on affinity to receptors related to sedation using a nationwide insurance claims database in Japan.Patients and Methods: We identified eligible patients by the following two criteria: (i) hospitalization due to schizophrenia (International Classification of Disease [ICD]-10 code: F20 or F25) in psychiatric wards between January 1st, 2005 and August 31st, 2017, and (ii) administration of HA high- or HA low-affinity drugs in the next month after discharge from the earliest hospitalization due to schizophrenia (index month). The primary endpoint was rehospitalization due to schizophrenia. The secondary endpoints were (i) involuntary rehospitalization, (ii) concomitant use of anxiolytics/hypnotics, mood stabilizers, and antiparkinsonian drugs, (iii) all-cause death, and (iv) medication discontinuation. Propensity score (PS) matching analysis was applied, and the hazard ratio (HR) of the event rate in the HA high-affinity drug group relative to the HA low-affinity drug group was calculated using Cox’s proportional hazards model.Results: Two thousand nine hundred and forty patients were identified as eligible patients. Among PS-matched patients (819 in each group), the HR in the HA high-affinity drug group compared with the HA low-affinity drug group was 1.018 (0.822– 1.260, P = 0.870). Other outcomes did not differ significantly between the two groups.Conclusion: No significant difference was observed in the rehospitalization risk due to schizophrenia associated with HA high-affinity antipsychotic drugs. Although this study was a retrospective PS-matched cohort study, the possibility of masking of the rehospitalization risk cannot be excluded because more than 80% of the patients were administered an anxiolytic/hypnotic at the time of admission.Keywords: schizophrenia, antipsychotics, sedative effect, rehospitalization, claim database, propensity score matching

Atopic dermatitis is a pruritic, eczematous dermatitis, the symptoms of which chronically fluctuate with remissions and relapses. Although a high psychosomatic and economic burden caused by atopic dermatitis is expected, few studies have been conducted estimating the cost of illness, including the self‐medication costs and productivity loss due to atopic dermatitis. The aim of this study was to conduct a cross‐sectional, Web‐based survey of the direct medical costs, self‐medication costs and productivity loss for adult atopic dermatitis patients, and estimate the burden of Japanese adult atopic dermatitis patients by disease severity. In a physician survey, the medical resource consumption related to medical treatments was surveyed by disease severity. The direct medical costs were calculated by multiplying the medical resource consumption and medical fee corresponding to each treatment. Based on the results of a patient survey, the self‐medication costs and productivity loss were estimated by sex and disease severity. Atopic dermatitis‐related productivity loss was calculated based on absenteeism, presenteeism, overall work impairment for employed workers and activity impairment for housewives. The nationwide estimations were calculated based on the estimated number of atopic dermatitis patients, employed workers with atopic dermatitis, and housewives with atopic dermatitis in their 20s–50s in Japan. Based on the surveys, all costs per patient and the scores increased with disease severity. The cost of illness for adult atopic dermatitis patients in Japan was estimated to be approximately JPY 3 trillion/year. Considering the physical and mental burdens, the burden of illness for adult atopic dermatitis was demonstrated to be vast.

In this study, the effects of ion-pair interaction energy and the alkyl chain length of acryl-ionic copolymers on the dispersion state of supergrowth single-walled carbon nanotubes (SG-SWCNTs) in c...

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.

Aims: The objective of the study is to evaluate the cost-effectiveness of percutaneous mitral valve repair (TMVr) with the MitraClip NT system (MitraClip procedure) for patients with sympto...

Background: Alzheimer’s disease dementia (ADD) is the leading cause of long-term care in Japan. Objective: This study estimates the annual healthcare and long-term care costs in fiscal year 2018 for adults over 65 years of age with ADD in Japan and the informal care costs and productivity loss for their families. Methods: Healthcare and long-term care costs for ADD were estimated according to the disease severity classified by the clinical dementia rating (CDR) score, using reports from a literature review. For the costs of time spent on caregiving activities, productivity loss for ADD family caregivers aged 20–69 and informal care costs for all ADD family caregivers were estimated. Results: The total healthcare cost of ADD was JPY 1,073 billion, of which 86% (JPY 923 billion) was attributed to healthcare costs other than ADD drug costs (JPY 151 billion). The healthcare costs other than ADD drug costs by severity were less than JPY 200 billion for CDR 0.5, CDR 1, and CDR 2, respectively, but increased to JPY 447 billion (48%) for CDR 3. The public long-term care costs were estimated to be JPY 4,783 billion, which increased according to the severity. Total productivity loss for ADD family caregivers aged 20–69 was JPY 1,547 billion and the informal care cost for all ADD family caregivers was JPY 6,772 billion. Conclusion: ADD costs have a significant impact on public-funded healthcare, long-term care systems, and families in Japan. To minimize the economic burden of ADD, prolonging healthy life expectancy is the key factor to address.

Koji Nitta,1,2 Gaku Tachibana,1,2 Ryotaro Wajima,1,2 Sachie Inoue,3 Tatsuya Ohigashi,4 Naomi Otsuka,4 Hiroaki Kurashima,4 Kazunori Santo,4 Masayo Hashimoto,4 Hidetoshi Shibahara,3 Mai Hirukawa,3 Kazuhisa Sugiyama2 1Department of Ophthalmology, Fukui-Ken Saiseikai Hospital, Fukui, Japan; 2Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan; 3CRECON Medical Assessment Inc., Tokyo, Japan; 4Japan Medical Affairs Group, Santen Pharmaceutical Co., Ltd., Osaka, JapanCorrespondence: Koji Nitta Email nitta.koji7001@fukui.saiseikai.or.jpPurpose: To maintain visual fields and quality of life over a lifetime, medical practice must be conducted taking into consideration not only visual field progression but also future visual field changes that occur over the patients’ expected lifespan. The purpose of this study is to investigate the feasibility of establishing a model that predicts prognosis, estimating the proportion of glaucoma patients with severe visual field defects.Patients and Methods: The data of 191 patients with primary open-angle glaucoma, with a predominance of normal-tension glaucoma, were used for this study. The model was developed based on patients’ backgrounds and risk factors, using Monte Carlo simulation. A “severe visual field defect” was defined as ≤-20 dB. The mean deviation (MD) value for 10,000 virtual patients in each simulation pattern (144 patterns) was calculated using a predictive formula to estimate the MD slope, and the effects of risk factors and intraocular pressure (IOP) reduction on the proportion of patients with severe visual field defects were evaluated.Results: Younger age, later-stage disease, more severe glaucomatous structural abnormalities and the presence of disc hemorrhage were associated with an increase in the progression rate of patients with severe visual field defects. Conversely, lower IOP was associated with a decrease in this rate.Conclusion: Combining regression analysis with Monte Carlo simulation could be a useful method for developing predictive models of prognosis in glaucoma patients.Keywords: glaucoma, epidemiology, prognosis, risk factors, simulation

Background Transcatheter aortic valve implantation (TAVI) is an innovative and effective treatment in high-surgical-risk (HR) and inoperable patients with symptomatic severe aortic stenosis. Objectives This cost-effectiveness analysis of transfemoral TAVI (TF-TAVI) compared with surgical aortic valve replacement (SAVR) conforms with the methodological guidelines for cost-effectiveness evaluation by the Ministry of Health, Labor, and Welfare in Japan. Methods The cost-effectiveness of TF-TAVI using SAPIEN XT was evaluated using a lifetime Markov simulation from the national payer perspective. Comparators were SAVR for HR patients and standard of care (SOC) for inoperable patients. A systematic literature review for clinical evidence of TF-TAVI and comparators was conducted. The evidence for TF-TAVI was derived from the SOURCE XT registry and Japanese post marketing surveillance. Because there was no literature directly or indirectly comparing TF-TAVI using SAPIEN XT with comparators, the comparator data were selected from relevant published studies, considering the similarity of study eligibility criteria and patient backgrounds (eg, age and surgical risk scores). Sensitivity analyses were used to validate the robustness of results. Results The incremental cost-effectiveness ratio of TF-TAVI versus SAVR for HR patients was ¥1.3 million/quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio of TF-TAVI versus SOC for inoperable patients was ¥3.5 million/QALY. Conclusions TF-TAVI was cost-effective when compared with SAVR for HR patients and when compared with SOC for inoperable patients, using a threshold of ¥5 million/QALY.

ObjectivesJapan 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.MethodsThe 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.ResultsInitiating 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.ConclusionsThere 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.

Pulmonary arterial hypertension (PAH) is a disease that imposes a significant burden on patients. Although multiple treatment options for PAH are available, head-to-head comparisons are difficult to conduct. Network meta-analysis (NMA) can be a useful alternative for direct comparison to estimate the relative effectiveness of multiple treatments. The objective of the present study was to conduct a systematic review and NMA to evaluate the relative effectiveness among oral PAH medications.Data collection was performed by searching the Cochrane Central Register of Controlled Trials (CENTRAL) and Ichushi-Web. Randomized controlled trials (RCTs) assessing at least 1 of the following 3 outcome measurements; 6-minute walk distance test (6MWD), WHO functional class (WHOFC), and mean pulmonary artery pressure (mPAP) were included (PROSPERO registration number: CRD42015016557). Outcomes were evaluated by estimating the differences in the mean change from baseline or by estimating the odds ratios. Analyses were performed using WinBUGS 1.4.3.Seven double-blind RCTs were eligible. NMA results showed similar improvements in 6MWD for all medications assessed. Bosentan and sildenafil caused a statistically significant improvement in WHOFC compared to other medications.The relative effectiveness of oral PAH medications could be compared using NMA, which suggested the superiority of bosentan and sildenafil in the improvement of WHOFC.

An objective method to predict individual visual field progression will contribute to realise personalised medication. The purpose of this study was to establish a predictive formula for glaucomatous visual field progression in patients with Primary open-angle glaucoma, mainly including normal tension glaucoma. This study was a large-scale, longitudinal and retrospective study including 498 eyes of 312 patients visiting from June 2009 to May 2015. In this analysis, 191 eyes of 191 patients meeting all eligible criteria were used. A predictive formula to calculate the rate of glaucomatous visual field progression (mean deviation slope) was obtained through multivariate linear regression analysis by adopting “Angle of Retinal Nerve Fibre Layer Defect” at the baseline, “Vertical Cup-Disc ratio” at the baseline, “Presence or absence of Disc Haemorrhage” during the follow-up period, and “Mean IOP change (%)” during the follow-up period as predictors. Coefficient of determination of the formula was 0.20. The discriminative ability of the formula was evaluated as moderate performance using receiver operating characteristic analysis, and the area under the curve was approximately 0.75 at all cut-off values. Internal validity was confirmed by bootstrapping. The predictive formula established by this type of approach might be useful for personalised medication.

Background The free radical scavenger edaravone has been reported useful for improvement in activities of daily living and for prevention of recurrent stroke in the edaravone versus sodium ozagrel in acute noncardioembolic ischemic stroke (EDO) trial. The aim of this report was to evaluate the cost-effectiveness of edaravone compared to the intravenous antiplatelet drug ozagrel sodium (ozagrel) for noncardioembolic stroke (non-CES) based on the EDO trial data. Methods A cost-effectiveness analysis was performed using the Markov model, which also incorporated the long-term course after the acute stage of non-CES. From the perspective of a health care payer, direct medical costs and nursing care costs were taken into account in the cost analysis. The quality-adjusted life year (QALY) served as an indicator of effectiveness. Simulation at 5 and 10 years after the onset of non-CES was carried out. The study involved 68-year-old patients with non-CES, selected against the EDO trial subject selection criteria. A 14-day treatment with edaravone 60 mg/day or ozagrel 160 mg/day was assumed as acute treatment for non-CES. Results The use of edaravone was associated with a reduction in total costs (0.51 million yen [$6,374] at 5 years and 0.64 million yen [$8,039]) at 10 years after the onset of non-CES) and improvement in QALYs (0.23 at 5 years and 0.38 at 10 years). Compared to ozagrel therapy, edaravone therapy was a cost-saving strategy for treating non-CES. Conclusions Compared to ozagrel therapy, edaravone therapy for non-CES is not only useful from a clinical viewpoint, but also valuable from a socioeconomic perspective.

Methotrexate (MTX), i.e., MTX-polygluatmate 1 (MTX-PG(1)), exerts its antirheumatic effects mainly byor = 6 (MTX-PG(2-7)) via folypolyglutamyl synthase in cells. The authors developed a new method using fluorescence polarization immunoassay to determine MTX-PG(1-7) concentrations in erythrocytes (RBC). MTX-PG(2-7) in RBC of rheumatoid arthritis (RA) patients receiving MTX was converted to MTX in the presence of plasma gamma-glutamyl hydrolase and mercaptoethanol at 37 degrees C. The MTX in RBC was extracted in a perchloric acid deproteinization step then on a solid-phase extraction column. The concentration of MTX was measured by TDX analyzer. The mean MTX recovery rate was 76.1% (n=8). The intraday and interday coefficients of variation were11.3% (n=8) and12.4% (n=3), respectively, at low and high concentrations (30-300 nmol/l). The calibration curve was linear over the range 30-300 nmol/l. The total concentration of MTX-PGs (mean+/-S.D.) in RBC obtained from 95 Japanese RA patient blood samples was 97.3+/-8.1 nmol/l for the MTX dose of 0.13+/-0.05 mg/week/kg. This newly developed method for the quantification of MTX-PGs in RBC is sensitive and accurate and can be applied for routine monitoring of MTX therapy in RA patients.

Objectives Overactive bladder (OAB) is characterized by involuntary contractions of the detrusor muscles of the bladder. The primary symptoms of OAB include urinary urgency and frequency, with or without urge incontinence. Despite the growing awareness of OAB as a chronic medical condition, little is known about the disease's economic burden. Therefore, in the present study, the costs associated with the management of OAB symptoms in Japan were estimated, and the potential cost saving by increasing the rate of physician visits in OAB population was analyzed. Methods To estimate the costs of OAB symptoms in Japan, we collected a variety of epidemiologic and economic literatures about OAB or urinary incontinence published by June, 2007. Three types of costs were considered in this estimation: 1. OAB treatment cost (pharmacological treatment cost, diagnostic cost and cost for physician visits), 2. direct cost (OAB-related cost [urinary tract infections, skin infections and fractures] and incontinence care cost [costs of pads, diapers and cleaning]), and 3. indirect cost (work loss due to absence from work and decrease in productivity). The analysis was conducted on community dwelling Japanese persons aged > or = 40 years, and assumed that OAB patients visited a hospital or a clinic once every four weeks. For the estimation of pharmacological treatment cost, four anticholinergic drugs (immediate-release oxybutynin (Pollakisu), propiverine (BUP-4), extended-release tolterodine (Detrusitol) and solifenacin (Vesicare)) were referred. Potential cost saving was estimated on the assumption that the hospital visit rate would increase from the current 22.7% to 35% and 50%, respectively. Results The number of persons with OAB symptoms and OAB patients was estimated at 8.6 million (4.6 million men, 4.0 million women) and 2.0 million (1.7 million men, 0.3 million women), respectively. The annual cost for OAB was estimated to be 956.2 billion yen (112,000 yen per one person with OAB symptoms). This cost included 180.9 billion yen (19%) for OAB treatment cost (including medication of 159.1 billion yen), 62 billion yen (6%) for OAB-related cost, 28.7 billion yen (3%) for incontinence care cost and 684.6 billion yen (72%) for work loss. Therefore, the cost for work loss accounted for the majority of OAB cost. The potential annual cost saving was estimated at 92.7 billion yen and 205.8 billion yen for the assumed hospital visit rate of 35% and 50%, respectively, and 88,000 yen per newly visiting OAB patient. Conclusion It was revealed that the economic impact imposed by OAB was enormous. It might be possible to reduce the cost for OAB by appropriate treatment for OAB population.

1, 1'-Carbonyldiimidazole (1) is a useful reagent for the preparation of arylacetonitriles (9) from 3-aryl-2-hydroxyiminopropionic acids (8), and 2, 2'-oxalyldi (o-sulfobenzimide) (2) can also be used for this purpose under essentially neutral conditions.

To identify the major factors predicting the response to Methotrexate (MTX) therapy in rheumatoid arthritis (RA) patients, we evaluated the relationship between the response to MTX and factors such as the concentration of MTX-polyglutamates (MTX-PGs) in erythrocytes (RBCs), genotypes of thymidylate synthase (TYMS) 5'-UTR (2R/3R) and 3'-UTR (-6/+6), 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, and other patient-related factors. Thirty-six Japanese RA patients were enrolled in this cohort study. The concentrations of MTX-PGs in RBCs were measured, and polymorphisms were determined using PCR-RFLP method. As an indicator of the accumulated capacity of MTX-PGs in the RBCs of each patient, the MTX dose/MTX-PGs (AC-MPG, l/week) was calculated. The response to MTX therapy was assessed using the MTX dose for a>or=50% decrease in CRP level (MTX dose for 50%CRP, mg/week), and the relationships between MTX dose for 50%CRP and various other factors were evaluated using multiple linear regression analysis. The MTX dose was 6.9+/-0.3 mg/week and the MTX-PGs concentration in RBCs was 97.3+/-8.1 nmol/l (n=36, blood samples=95, mean+/-S.D.). The range of MTX dose for 50%CRP was 2.0-13.0 mg/week. Most individual AC-MPG levels showed no change during the evaluation period (coefficient of variation=5.9%). Based on the results of multiple linear regression analysis, AC-MPG, TYMS 3'-UTR (-6/+6), and ESR at the start of MTX therapy were associated with the MTX dose for 50%CRP. AC-MPG, TYMS 3'-UTR (-6/+6), and ESR might be the major predictive factors for the response to MTX therapy in Japanese RA patients.

1, 1'-Carbonyldiimidazole (1) is a useful reagent for the preparation of arylacetonitriles (9) from 3-aryl-2-hydroxyiminopropionic acids (8), and 2, 2'-oxalyldi (o-sulfobenzimide) (2) can also be used for this purpose under essentially neutral conditions.

Objectives: We investigated the four polymorphisms of the 5,10-methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TYMS) genes that are related to the pharmacologically active sites of methotrexate for the treatment of rheumatoid arthritis in 102 healthy Japanese adults and assessed the possibility of ethnic and gender differences. Methods: Polymorphisms of MTHFR C677T, A1298C, the two or three 28-bp tandem repeats in the TYMS 5´-untranslated regions (UTR), and the 6-bp deletion/insertion in the TYMS 3´-UTR were measured using polymerase chain reaction with restriction fragment length polymorphism method. Published data on allelic frequencies by ethnic group and gender were collected from Medline. Results: Allelic frequencies in healthy Japanese adults were: MTHFR 677T allele 41%, MTHFR 1298C allele 22%, TYMS 5´-UTR 3R allele 84%, and TYMS 3´-UTR-6-bp allele 59%. Significant differences were found in the distribution of MTHFR C677T between black and Japanese populations, of TYMS 5´-UTR alleles between Caucasian or black and Japanese populations, and of TYMS 3´-UTR alleles between Caucasian and Japanese populations (p

Gln-Val-Val-Ala-Gly is a sequence which is common in cysteine protease inhibitors. Poly(ethylene glycol) hybrids of Gln-Val-Val-Ala-Gly analogs were prepared by the solid phase method by fluorenylmethyloxycarbonyl chemistry. The hybrid formation of Gln-Val-Val-Ala-Gly resulted in improvement of the solubility and also in enhancement of the inhibitory effect of the peptide on papain. In addition, the hybrid formation of Gln-Val-Val-Ala-Gly analogs resulted in the enhancement of the inhibitory effect of the peptide analogs.

Laminin-related peptide poly(ethylene glycol) hybrid, Tyr-Ile-Gly-Ser-Arg-aminopoly(ethylene glycol) was prepared by the solution method and carboxylated poly(ethylene glycol)-Tyr-Ile-Gly-Ser-Arg was prepared by the solid phase method. Their inhibitory effects on experimental tumor metastasis were examined in mice. The inhibitory effect of Tyr-Ile-Gly-Ser-Arg was significantly potentiated by hybrid formation with poly(ethylene glycol) either at amino- or carboxyl terminals of the peptide. Of the hybrids, Tyr-Ile-Gly-Ser-Arg-amino(polyethylene glycol) #6000 hybrid exhibited about 10 times more potent anti-metastatic effect than the peptide itself. The inhibitory effect of a mixture of the carboxylated poly(ethylene glycol) hybrid and Arg-Gly-Asp-aminopoly(ethylene glycol) hybrid also exhibited an inhibitory effect.