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Utilizing a range of ethnographic data from an AIDS hotline, a women's shelter, a night club, AIDS campaigns, news articles, and interviews with health bureaucrats, this paper explores the history of AIDS in Japan and the ways in which official practices reproduce systems of domination. This paper examines the official categories of "foreign woman" and "prostitution" as discursive strategies of containment, and argues that nationalist discourses and representations of sexuality are closely linked in maintaining relations of power. [ABSTRACT FROM AUTHOR]

Health care expenditure studies of the Organization for Economic Cooperation and Development (OECD) countries remain important because their findings often suggest cost containment and other policy initiatives. This paper focuses on the compatibility of OECD health data with the "expenditure inertia" (or lagged adjustments) hypothesis, by modeling individual country time-series data of 21 nations for the 1960-1993 period. Maximum likelihood estimates of the Box-Cox transformation regression models reveal that: (a) the hypothesized impact of health "expenditure inertia" is both pervasive and strong, averaging 0.64 across the countries; (b) the real GDP elasticities of health care expenditures vary widely among the countries and average 0.34 in the short run--implying that health care is a necessity; (c) the long run GDP elasticities are less than 1 in 8 countries, unitary elastic in 8 countries and elastic in 5 countries--suggesting that health care is not universally a necessity or a luxury commodity for the OECD countries; (d) physician-inducement effects (dis-inducement in a few countries) are weak, with a mean elasticity estimate of 0.17; and (e) no unique functional form approximation model is globally compatible with the data across the countries. Health care cost containment policy implications of these findings are explored. [ABSTRACT FROM AUTHOR]

Introduction: Rotarix™, GSK's live attenuated rotavirus vaccine, was introduced in Japan in 2011. A recent trend in reduction of rotavirus gastroenteritis (RVGE) due to this vaccine was described. However, an observed/expected analysis showed a temporal association with intussusception within 7 days post dose 1.Objective: In this paper, we compare the benefit and risk of vaccination side-by-side in a benefit-risk analysis.Methods: The number of vaccine-preventable RVGE-associated hospitalizations and deaths (benefit) and intussusception-associated hospitalizations and deaths (risk) following two doses of Rotarix™ in Japan was compared using simulations. Source data included peer-reviewed clinical and epidemiological publications, Japanese governmental statistics (Statistics Bureau, Ministry of Internal Affairs and Communications), and market survey data.Results: For a birth cohort of 1 million vaccinated Japanese children followed for 5 years, the benefit-risk analysis suggested that the vaccine would prevent ~17,900 hospitalizations and ~6.3 deaths associated with RVGE. At the same time, vaccination would be associated with about ~50 intussusception hospitalizations and ~0.017 intussusception deaths. Therefore, for every intussusception hospitalization caused by vaccination and for one intussusception-associated death, 350 (95 % CI 69-2510) RVGE-associated hospitalizations and 366 (95 % CI 59-3271) RVGE-associated deaths are prevented, respectively, by vaccination.Conclusions: The benefit-risk balance for Rotarix™ is favorable in Japan. From a public health perspective, the benefits in terms of prevented RVGE hospitalizations and deaths for the vaccinated population far exceed the estimated risks due to intussusception. [ABSTRACT FROM AUTHOR]

We examine the length of time between when an individual feels sick and when he/she visits a doctor using survival analysis to capture the dynamic aspects of this behavior. If the disease is light, actions such as OTC medicine or sick leave are alternatives to visiting a clinic or a hospital immediately. The timing of the visit depends only the person's decision, not on a doctor's, so we can limit discussion to the effect of ex-post moral hazard excluding physician induced demand. Participants were asked to keep a log of illness-related behavior such as dates of episodes, subjective symptoms, sick leaves, and medical treatment at hospitals. Neither the copayment rate nor access cost had a significant effect on the behavior of visiting a doctor, whereas available alternatives delay the timing of a visiting. Severe symptoms and fever hastened the time. The results suggest that the traditional argument about ex-post moral hazard is somewhat misleading. [ABSTRACT FROM AUTHOR]

This paper is an attempt to explore the socio-cultural significance of deliberately disguising schizophrenia as neurasthenia, neurosis or malfunction of autonomic nervous system. To understand its significance, the socio-cultural background of Japanese attitudes toward mental illness and Japan's mental health care system is also examined from a non-Western standpoint. [ABSTRACT FROM AUTHOR]

Introduction: This MONONOFU trial subgroup analysis evaluates the efficacy of lasmiditan across patient and migraine characteristics in Japanese patients with migraine.Methods: MONONOFU trial was a multicenter, randomized, double-blind, placebo-controlled study. The patients were randomly assigned in a 3:7:6:7 ratio to receive lasmiditan 50 mg, 100 mg, 200 mg, or placebo for a single migraine attack within 4 h of pain onset. Efficacy of lasmiditan vs placebo was evaluated at 2 h post dose for proportion of patients with headache pain freedom. Efficacy was assessed across patient characteristics (age, sex, body weight, cardiovascular risk factors (CVRF), and comorbidity of tension-type headache), migraine disease characteristics (history of migraine with aura, migraine prevention therapy, triptan response, and triptan use or nonuse), and migraine attack characteristics (headache severity, aggressive headache, attack during perimenstrual period, time to dosing, time of dosing, experienced treatment-emergent adverse event (TEAE) of dizziness, and experienced TEAE of somnolence). Logistic regression was used; all subgroup analyses were not analyzed with multiplicity-adjusted statistical tests.Results: Treatment-by-subgroup interactions (by each arm) were not significant (p ≥ 0.05) for pain freedom at 2 h post dose across all patient subgroups and lasmiditan doses, except for CVRF (100 mg and 200 mg), migraine with aura (50 mg), triptan response (50 mg), and time to dosing (200 mg). Treatment-by-subgroup interactions (by overall) were not significant (p ≥ 0.05) for pain freedom at 2 h post dose across all patient subgroups, except for CVRFs. Higher proportions of patients were pain free at 2 h post dose when treated with lasmiditan (50 mg, 100 mg, and 200 mg) versus placebo, irrespective of most patient characteristics, migraine disease characteristics, and migraine attack characteristics.Conclusion: Although few interactions were observed, lasmiditan could be a promising acute treatment option in a wide range of Japanese patients with migraine, as efficacy is not generally influenced by patient and migraine characteristics. [ABSTRACT FROM AUTHOR]

Background: Endocytoscope systems (ECS) can visualize cellular nuclei of the mucosa of the gastrointestinal tract and are predicted to provide real-time microscopic diagnosis. However, their practical diagnostic performance remains unclear. Therefore, we conducted a multicenter prospective study to evaluate the visualization of superficial esophageal neoplasm in vivo using an ECS, and its diagnostic capability.Methods: The study target was histologically confirmed squamous cell carcinoma (SCC) and high-grade intraepithelial neoplasia (HGIN). An integrated ECS was used to obtain ECS images. In each patient, three ECS images of cancerous and corresponding noncancerous regions were selected for evaluation. A pathological review board of five certified pathologists made the final diagnosis of the images. The primary endpoint was the sensitivity of ECS diagnosis by pathologists.Results: ECS images of 68 patients were assessed: 42 lesions were mucosal SCC, 13 were submucosal SCC, and 13 were HGIN. The rate of assessable images was 96% (95% CI 87.6-99.1). The sensitivity of ECS diagnosis by pathologists was 88% (95% CI 77.2-94.5).Conclusions: ECS can provide high-quality images of cancerous lesions and a high diagnostic accuracy by pathologists, and could be useful for real-time endoscopic histological diagnosis of SCC and HGIN.Trial Registration: The UMIN Clinical Trials Registry Identification Number: 000004218. [ABSTRACT FROM AUTHOR]

This study examined the association of green tea consumption with influenza among Japanese workers in the Kanto and Tokai areas. We conducted a case-control study in a cohort of 4302 workers. Consumption frequency of green tea in 2011 and physician-diagnosed influenza that occurred over the winter season from November 2011 through April 2012 were ascertained using a self-administered questionnaire. Two controls matched by company, sex, and age (and checkup date in one company) were randomly selected for each case. Odds ratio of influenza were estimated by conditional logistic regression. One hundred and seventy-nine cases and 353 controls with complete data were included in the analysis. Green tea consumption was significantly associated with decreased odds of developing influenza; the multivariable-adjusted odds ratio for green tea consumption of ≥5 cups/week was 0.61 (95% CI 0.39-0.95) compared with <1 cup/week (P for trend = 0.028). When analysis was restricted to cases confirmed using a diagnostic kit, the corresponding value was 0.68 (95% CI 0.39-1.18; P for trend = 0.16). Our data suggest that green tea consumption is associated with a lower risk of influenza. The present findings require confirmation in large-scale prospective studies using diagnostic tool for influenza infection. [ABSTRACT FROM AUTHOR]

Background/objectives: The association of fermented soy products, separately from total soy products, with cardiovascular disease (CVD) and total cancer has not been reported. We examined this association in a population-based prospective cohort study in Japan.Subjects/methods: We studied 79,648 participants (42,788 women; 36,860 men) aged 45-74 years without a history of cancer, myocardial infarction, or stroke. Participants completed a food frequency questionnaire (1995-1998) and were followed to 2009-2012. Cox proportional hazards regression analysis was used to calculate the hazard ratios (HR) and 95% confidence intervals (CI) of incidence of CVD and total cancer according to quartiles of total soy products, nonfermented soy products, fermented soy products, miso soup, natto, total isoflavones from soy products, isoflavones from nonfermented soy products, and isoflavones from fermented soy products.Results: In women, we observed a significant inverse association between fermented soy product intake and the risk of CVD (multivariate HR in the highest compared with the lowest quartile of fermented soy product intake: 0.80; 95% CI: 0.68, 0.95; P for trend = 0.010), and also found significant inverse associations for natto and isoflavones among fermented soy products. In site-specific analysis, we observed a similar, significant inverse association between fermented soy product intake and the risk of stroke in women. We found no significant association between any soy product and risk of CVD in men or total cancer in both sexes.Conclusions: Intake of fermented soy products such as natto was inversely associated with the risk of CVD in women. [ABSTRACT FROM AUTHOR]

Texture-modified diets (TMD) is often used in clinical practices for the treatment and prevention of pneumonia. However, it is unclear how stages of TMD affect the swallowing ability and nutritional status in patients with pneumonia. This study aimed to investigate the relationship between the various stages of TMD and swallowing ability and nutritional status in older inpatients with pneumonia. In this retrospective cohort study, data for patients aged ≥ 65 years with pneumonia were obtained from the Japan Rehabilitation Nutrition Database. We performed coarsened exact matching with Mini Nutritional Assessment Short Form (MNA-SF) on admission. Ultimately, 218 patients (mean age 82.9 ± 9.8 years) were included and divided into two groups based on the stages of TMD in the facility: multiple TMD (M-TMD) group (stages of TMD ≥ 6) and control group (stages of TMD < 6). The main outcome was the rate of improvement in the Food Intake Level Scale (FILS) and the maintenance or improvement in the MNA-SF score. We used the within-hospital correction with generalized estimation equations that are commonly used to analyze clustered data while correcting for confounding factors by clustering. Multivariate multiple logistic analysis showed that M-TMD was independently associated with FILS improvement rate and the maintenance or improvement in the MNA-SF score (odds ratio [OR] 3.252; 95% confidence interval [CI] 1.602-6.601; p = 0.001 and OR 1.873; 95% CI 1.054-3.330; p = 0.032, respectively). M-TMD in the facility was associated with the maintenance or improvement in swallowing ability and the nutritional status of patients with pneumonia. [ABSTRACT FROM AUTHOR]

Hypophosphatasia (HPP) is highly variable in clinical expression and is generally classified into six subtypes. Although it would be beneficial to be able to predict the clinical course from the ALPL genotype, studies on this issue are limited. Here, we aimed to clarify the features of Japanese HPP and the relationships between genotype and clinical manifestations. We analyzed 98 unrelated Japanese patients to investigate the percentage of each clinical form, frequently detected mutations, and the relationship between the genotype and phenotype. Some of the identified mutants were characterized by transfection experiments. Perinatal severe form was the most frequent (45.9%), followed by perinatal benign form (22.4%). Among the 196 alleles, p.Leu520ArgfsX86 (c.1559delT) was detected in 89 alleles, and p.Phe327Leu (c.979T>C) was identified in 23 alleles. All of the homozygotes for p.Leu520ArgfsX86 were classified into perinatal severe form, and patients carrying p.Phe327Leu in one of the alleles were classified into perinatal benign or odonto HPP. Twenty of the 22 patients with perinatal benign HPP were compound heterozygous for p.Phe327Leu and another mutation. Most patients with odonto HPP were found to be monoallelic heterozygotes for dominant-negative mutations or compound heterozygotes with mutants having residual activity. The high prevalence of p.Leu520ArgfsX86 and p.Phe327Leu mutations might underlie the high rate of perinatal severe and perinatal benign forms, respectively, in Japanese HPP. Although ALPL genotyping would be beneficial for predicting the clinical course to an extent, the observed phenotypical variability among patients sharing the same genotypes suggests the presence of modifiers. [ABSTRACT FROM AUTHOR]

Background: Continuous regional arterial infusion (CRAI) of protease inhibitor nafamostat mesilate (NM) is used in the context of predicted severe acute pancreatitis (SAP) to prevent the development of pancreatic necrosis. Although this therapy is well known in Japan, its efficacy and safety remain unclear.Methods: This investigator-initiated and -driven, multicenter, open-label, randomized, controlled trial (UMIN000020868) enrolled 39 patients with predicted SAP and low enhancement of the pancreatic parenchyma on computed tomography (CT). Twenty patients were assigned to the CRAI group, while 19 served as controls and were administered NM at the same dose intravenously (IV group). The primary endpoint was the development of pancreatic necrosis as determined by CT on Day 14, judged by blinded central review.Results: There was no difference between the CRAI and IV groups regarding the percentages of participants who developed pancreatic necrosis (more than 1/3 of the pancreas: 25.0%, range 8.7-49.1% vs. 15.8%, range 3.4-39.6%, respectively, P = 0.694; more than 2/3 of the pancreas: 20%, range 5.7-43.7% vs. 5.3%, range 0.1-26.0%, respectively, P = 0.341). The early analgesic effect was evaluated based on 24-h cumulative fentanyl consumption and additional administration by intravenous patient-controlled analgesia. The results showed that the CRAI group used significantly less analgesic. There were two adverse events related to CRAI, namely bleeding and splenic infarction.Conclusions: CRAI with NM did not inhibit the development of pancreatic necrosis although early analgesic effect of CRAI was superior to that of IV. Less-invasive IV therapy can be considered a viable alternative to CRAI therapy. [ABSTRACT FROM AUTHOR]

When children around 2-year-old show leg bowing without lower-limb radiographic abnormalities for rickets, the leg bowing is classified as "physiologic" genu varum without conducting a blood test. However, it has recently been suggested that toddlers who are diagnosed with physiologic genu varum may in fact have some form of bone metabolic disorder. In this 1:2 case-control study, blood samples were obtained from 33 toddlers with genu varum without radiographic abnormalities for rickets and 66 age- and gender-matched healthy children. Serum alkaline phosphatase (sALP), intact parathyroid hormone (siPTH), 25-hydroxy vitamin D [s25(OH)D], calcium (sCa), and inorganic phosphate (sP) were measured. s25(OH)D of the subjects with genu varum (24.8 ng/ml) were significantly lower than those of the control (33.6 ng/ml) (p < 0.001). The frequency of vitamin D insufficiency/deficiency (< 20 ng/ml) of the subjects with genu varum (39%) was significantly higher than that in the control (14%) (p = 0.004) (odds ratio by vitamin D insufficiency/deficiency: 4.1 [1.5-11.1, p = 0.004]). sCa in subjects with genu varum (10.2 ng/ml) were significantly higher than in control (9.8 ng/ml) (p < 0.001), as were sALP (1057 IU/l) and siPTH (28.4 pg/ml) (740 IU/l and 8.8 pg/ml in control, respectively; p < 0.001). siPTH levels were associated with s25(OH)D levels in subjects with genu varum (r = - 0.57, p < 0.001), while no association was observed in the control (r = 0.11, p = 0.36). Genu varum without radiographic abnormalities of rickets was associated with both vitamin D and bone-metabolic disorders in toddlers, indicating that physiologic genu varum is not a physiologic condition in toddlers. [ABSTRACT FROM AUTHOR]

Background: The McMaster Health Utilities Index Mark 3 (HUI3) is a generic multi-attribute, preference-based system for assessing health-related quality of life (HRQOL). This study describes the translation procedures and cultural adaptation of the Japanese HUI3 and its measurement properties in a community sample. Methods: The Japanese HUI3 was developed through forward and back translations in cooperation with the developers of the HUI. Acceptability, comprehensibility of questionnaires, and test-retest reliability were assessed. In a community survey of a total of 3860 people (age: 41 ± 14.3, male/female: 2651/1209), the Canadian scoring function was used to calculate utility scores. Construct validity was assessed by examining the relationship between 20 personal characteristics and utility scores. Results: Linear regression estimates demonstrated a significant negative relation between HUI3 utility score and low education, male gender, poor interpersonal relationships, older age, and a higher number of chronic diseases. Single-attribute utility scores were associated with chronic conditions in the manner expected. The community samples were relatively healthy. More than 90% of the respondents were distributed in levels 1 and 2 in all attributes except cognition. Interpretability of utility score was assessed by estimation of the relationship between visual analogue scale (VAS) and the self-rated health and utility score. Independence of attributes was assessed. For only 3 of the 28 possible cross-comparisons among the 8 attributes were correlations coefficients greater than 0.25. Conclusion: Translation and adaptation of the HUI3 questionnaire into Japanese was successful, but the sample size and selection bias limit the interpretation of our study conclusions. [ABSTRACT FROM AUTHOR]

Purpose: Patient-level data from two large studies of the Zilver PTX drug-eluting stent (DES) with long-term follow-up and concurrent non-drug comparator groups were analyzed to determine whether there was an increased mortality risk due to paclitaxel.Methods: Data from the Zilver PTX randomized controlled trial (RCT) and Zilver PTX and bare metal stent (BMS) Japan post-market surveillance studies were analyzed. Five-year follow-up is complete in both DES studies; follow-up for the BMS study was limited to 3 years and is complete. Kaplan-Meier analyses assessed mortality. A Cox proportional hazards model identified significant factors related to mortality.Results: In the RCT, there were 336 patients treated with the DES and 143 patients treated with percutaneous transluminal angioplasty (PTA) or BMS. In Japan, there were 904 DES patients and 190 BMS patients. There was no difference in all-cause mortality for the DES compared to PTA/BMS in the RCT (19.1% DES versus 17.1% PTA/BMS through 5 years, p = 0.60) or Japan (15.8% DES versus 15.3% BMS through 3 years, p = 0.89). Cox proportional hazard models revealed that age, tissue loss, and congestive heart failure were significantly associated with mortality in the RCT, and critical limb ischemia, age, renal failure, and gender were significantly associated with mortality in Japan (all p < 0.05). Neither treatment with Zilver PTX (p = 0.46 RCT, p = 0.49 Japan) nor paclitaxel dose (p = 0.86 RCT, p = 0.07 Japan) was associated with mortality.Conclusion: Analyses of the Zilver PTX patient-level data demonstrated no increase in long-term all-cause mortality.Level Of Evidence: Zilver PTX RCT: Level 1, randomized controlled trial; Japan PMS studies: Level 3, post-market surveillance study. [ABSTRACT FROM AUTHOR]

Background: Vedolizumab (VDZ) was approved by the Japanese Ministry of Health, Labor and Welfare in 2018 for the treatment of patients with moderate-to-severe active ulcerative colitis (UC). The comparative cost-effectiveness of VDZ compared with other biologics is unknown in Japan. This information could be useful for decision makers at the time of repricing biologics for the treatment of patients with moderate-to-severe UC.Objective: The aim was to assess the cost-effectiveness of VDZ versus other branded biologics for the treatment of patients with moderate-to-severe UC who were anti-tumor necrosis factor (TNF)-naïve, from the Japanese public healthcare payer perspective.Methods: A hybrid decision tree/Markov model was developed to predict the number of patients who achieved response and remission at the end of the induction phase and sustained it during the maintenance phase, translating this into quality-adjusted life-years (QALYs) and costs. Treatment-related adverse events, discontinuation and surgery, and their impact on QALYs and costs were also modeled. A systematic literature review and network meta-analysis were conducted to estimate the comparative efficacy of each treatment versus placebo. Rates of adverse events, surgery, surgery complications, and utilities were from the literature. Costs (2018 Japanese yen) were obtained from the Japanese National Health Insurance drug price list and medical fee table and local claims databases. Clinical and economic outcomes were projected over a lifetime and discounted at 2% annually.Results: Over a lifetime, VDZ yielded greater QALYs and cost savings compared with golimumab and was cost-effective compared with adalimumab and infliximab (incremental cost-effectiveness ratios ¥4,821,940 and ¥4,687,692, respectively). Deterministic and probabilistic analyses supported the robustness of the findings in the base-case analysis, indicating that VDZ was either dominant or cost-effective in most scenarios and replications. The main limitations of this analysis include excluding tofacitinib and infliximab biosimilar as comparators, health-state utility estimates were obtained from population studies in the United Kingdom, and the impact of subsequent (i.e., second-line) biologic treatment was not evaluated.Conclusion: Our analysis suggests that VDZ is dominant or cost-effective compared with other branded biologics for the treatment of anti-TNF-naïve patients with moderate-to-severe UC in Japan. [ABSTRACT FROM AUTHOR]

Background: Gastroesophageal reflux disease (GERD) can be treated using a vonoprazan-first strategy (first-line treatment with vonoprazan), or esomeprazole-first/rabeprazole-first strategies (first-line treatment with proton-pump inhibitors [PPIs], esomeprazole/rabeprazole, followed by a switch to vonoprazan). This cost-utility analysis used long-term simulation modeling to evaluate the cost-effectiveness of a vonoprazan-first strategy compared with the esomeprazole-first and rabeprazole-first strategies.Methods: A Markov simulation model was developed to evaluate the cost-effectiveness of vonoprazan-first, esomeprazole-first, and rabeprazole-first strategies, comprising healing and maintenance therapies, over 5 years (4-week cycles). Healing therapy began with the administration of a normal dose of drug per real-world practice. If patients were not healed endoscopically, either a longer duration of healing therapy was provided (vonoprazan), the dose was increased (rabeprazole), or patients were switched to vonoprazan (immediately for esomeprazole, and after dose-escalation for rabeprazole, respectively). Healed patients received maintenance (lower/same dose as healing therapy). Recurrence resulted in re-challenge with healing therapy. Transition probabilities were derived from the results of indirect comparisons (network meta-analysis) and costs calculated from the Japanese payer perspective. Outcomes were defined as quality-adjusted life years (QALYs), with utilities based on published values.Results: Expected costs of the vonoprazan-, esomeprazole-, and rabeprazole-first strategies were ¥36,194, ¥76,719, and ¥41,105, respectively, over 5 years. QALY gains for vonoprazan-first strategy versus the esomeprazole- and rabeprazole-first strategies were 0.014 and 0.003, respectively. Both estimated incremental cost-effectiveness ratios were dominant and robust to two sensitivity analyses.Conclusions: Vonoprazan-first strategy increased QALYs and appeared to be cost-effective for GERD patients compared with the esomeprazole- or rabeprazole-first strategies. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested that a healthy lifestyle (HL) may prolong the years of life spent in good health. However, the impact of HL on disability-free survival (DFS) among the elderly is still uncertain.Objective: To investigate the relationship between HL and DFS in the general elderly population.Design: Prospective cohort study with a 10-year follow-up (2006-2016).Participants: 9910 community-dwelling elderly people (≥ 65 years).Main Measures: A HL index derived by summing the number of HL behaviors. Data on incident disability were retrieved from the public Long-term Care Insurance database. Multivariate-adjusted 50th percentile differences (PDs) in age at disability or death (months) and their 95% CIs were estimated with the Laplace regression model.Key Results: During the 10 years, 4562 disability or death events occurred. Participants who adhered to all three HL behaviors lived 17.1 (95% CI 12.7, 21.5) months longer without disability than those who adhered to zero or one. Each 1-point increase of the index score conferred 8.8 months additional life without disability. The tendency for the 50th PDs to increase with a higher HL index score did not differ according to age (< 75 or ≥ 75 years), sex, or the presence of chronic conditions (none, or ≥ 1 chronic condition).Conclusions: A combination of HL behaviors may substantially increase DFS, even for late-elderly (≥ 75 years), or elderly people with chronic conditions. [ABSTRACT FROM AUTHOR]

Purpose: A prospective, multicenter post-market surveillance study in Japan evaluated the 2-year safety and effectiveness of the DES in real-world patients with complex femoropopliteal artery lesions.Methods: There were no exclusion criteria, and consecutive symptomatic patients with femoropopliteal lesions treated with the DES were enrolled in the study. Clinically driven target lesion revascularization (TLR) was defined as reintervention performed for > 50% diameter stenosis after recurrent clinical symptoms of peripheral arterial disease. Clinical benefit was defined as freedom from persistent or deteriorating ischemic symptoms. Patency was evaluated by duplex ultrasound where physicians considered this standard of care.Results: In this study, 905 patients were enrolled at 95 institutions in Japan. There were numerous comorbidities including a high incidence of diabetes (58.8%) and chronic kidney disease (43.6%). Additionally, 21.4% of patients were classified with critical limb ischemia. Lesions were complex, with an average length of 14.6 ± 9.6 cm (range 0.5-40 cm), 41.5% total occlusions, and 18.7% in-stent restenosis. In total, 1861 DES were placed in 1080 lesions. Two-year follow-up was obtained for > 90% of eligible patients. Freedom from TLR was 83.7%, and clinical benefit was 80.0% through 2 years. The 2-year primary patency rate was 70.3%. Rutherford classification significantly improved (p < 0.01), with approximately 80% of patients classified as Rutherford class 0 or 1 at 2 years.Conclusion: Despite more challenging lesion characteristics, 2-year results from the current study are similar to outcomes from the previous Zilver PTX studies, confirming the efficacy of the Zilver PTX DES in a complicated femoropopliteal lesion (Zilver PTX Post-Market Study in Japan; NCT02254837).Level Of Evidence: Post-market surveillance study, Level III. [ABSTRACT FROM AUTHOR]

Introduction: Patients with cluster headache (CH), the most common trigeminal autonomic cephalalgia, often face delayed diagnosis, misdiagnosis and mismanagement.Objectives: To identify, appraise and synthesise clinical studies on the delays in diagnosis and misdiagnosis of CH in order to determine its causes and help the management of this condition.Methods: The systematic review was prepared, conducted and reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis. It was registered with International Prospective Register of Systematic Reviews. A systematic search of different electronic databases (Medline, EMBASE, PsycINFO, PubMed, CINAHL, BNI, HMIC, AMED, HBE and Cochrane Library) was carried out in May 2017. Reference lists of relevant articles were hand searched.Results: The search identified 201 unique studies. Fifteen studies met the inclusion criteria of which 13 case series studies and two survey studies. Nine studies assessed the delays in diagnosis and misdiagnosis of CH, five studies the delays in diagnosis and one study the misdiagnosis of CH. The studies included 4661 patients. Delays in diagnosis, misdiagnosis and mismanagement have been reported in many European countries, Japan and in the USA with well-developed health services. The patients with CH often visited many different clinicians, surgeons and dentists and received multiple diagnosis prior to being correctly diagnosed.Conclusion: This systematic review shows that the delays in the diagnosis of CH are a widespread problem, the time to diagnosis still vary from country to country and both patients and physicians are responsible for the delays in diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: There is little knowledge about how hospitals can best handle disruptions that reduce post-anesthesia care unit (PACU) capacity. Few hospitals in Japan have any PACU beds and instead have the anesthesiologists recover their patients in the operating room. We compared postoperative recovery times between a hospital with (University of Iowa) and without (Shin-yurigaoka General Hospital) a PACU.Methods: This historical cohort study included 16 successive patients undergoing laparoscopic gynecologic surgery with endotracheal intubation for general anesthesia, at each of the hospitals, and with the hours from OR entrance until the last surgical dressing applied ≥ two hours. Postoperative recovery times, defined as the end of surgery until leaving for the surgical ward, were compared between the hospitals.Results: The median [interquartile range] of recovery times was 112 [94-140] min at the University of Iowa and 22 [18-29] min at the Shin-yurigaoka General Hospital. Every studied patient at the University of Iowa had a longer recovery time than every such patient at Shin-yurigaoka General Hospital (Wilcoxon-Mann-Whitney, P < 0.001). The ratio of the mean recovery times was 4.90 (95% confidence interval [CI], 4.05 to 5.91; P < 0.001) and remained comparable after controlling for surgical duration (5.33; 95% CI, 3.66 to 7.76; P < 0.001). The anesthetics used in the Iowa hospital were a volatile agent, hydromorphone, ketorolac, and neostigmine compared with the Japanese hospital where bispectral index monitoring and target-controlled infusions of propofol, remifentanil, acetaminophen, and sugammadex were used.Conclusions: This knowledge can be generally applied in situations at hospitals with regular PACU use when there are such large disruptions to PACU capacity that it is known before a case begins that the anesthesiologist likely will need to recover the patient (i.e., when there will not be an available PACU bed and/or nurse). The Japanese anesthesiologists have no PACU labour costs but likely greater anesthesia drug/monitor costs. [ABSTRACT FROM AUTHOR]

Background: Sporadic nonampullary duodenal epithelial tumors (NADETs) are uncommon, and thus their clinicopathological features have not been fully assessed.Aims: In this study, we have analyzed a series of early sporadic NADETs, focusing on various immunohistological features.Methods: We conducted a multicenter retrospective analysis of 68 patients with endoscopically resected sporadic NADETs. Associations between immunohistological features and clinicopathological features were statistically analyzed.Results: The 68 patients consisted of 46 men (68%) and 22 women (32%) with a mean age of 60.7 ± 12.2 years (range 37-85 years). The 68 tumors were composed of 39 adenomas (57%) and 29 early-stage adenocarcinomas (43%). Duodenal adenocarcinomas were larger in size than adenomas and had papillary architecture in their pathological diagnosis with statistical significance. Duodenal adenocarcinomas also demonstrated a significantly higher expression of gastric markers (MUC5AC and MUC6) and a higher MIB-1 index. Duodenal adenomas were contrastively apt to express intestinal markers (MUC2, CDX1 and CDX2). Of the 68 cases analyzed, there were only 3 tumors positive for p53 staining, all of which were adenocarcinoma. When 7 submucosal invasive cancers and 21 intramucosal cancers were compared, submucosal invasion was positively associated with expression of MUC5AC. Also, submucosal invasion showed strong association with double-positivity of MUC5AC and MUC6.Conclusions: Our results indicate that immunohistochemical evaluation is useful for predicting malignant potential of NADETs, especially focusing on the expression of gastrointestinal markers. [ABSTRACT FROM AUTHOR]

Purpose: The Soave procedure (SO) is performed most commonly for Hirschsprung disease. SO reduces the risk of injury to the pelvic structures; however, a residual aganglionic muscle cuff could interfere with bowel movement and lead to obstructive enterocolitis. The Swenson procedure is considered ideal in terms of peristalsis. Currently, laparoscopic surgery provides better visualization and facilitates precise dissection, possibly leading to feasible performance of the laparoscopic modified Swenson procedure (SW). We present our operative technique and the efficacy of the SW compared with that of SO.Methods: We retrospectively reviewed the records of 16 and 27 patients who underwent SW and SO, respectively, between 2012 and 2017.Results: Operative time, blood loss, length of stay, and frequency of bowel movements showed no significant difference between the two groups. In the SW group, temporary dysuria occurred in one patient, postoperative enterocolitis in two, wound infection in one, and severe perianal excoriation in four, whereas in the SO group, obstructive symptoms occurred in three patients, small-bowel obstruction in one, and severe perianal excoriation in three. The complications and outcomes were comparable between both groups.Conclusion: Laparoscopic SW was safe and feasible for the short-term follow-up outcomes. [ABSTRACT FROM AUTHOR]

Background/objectives: We studied the ecologic relationships of food groups, macronutrients, eating patterns, and an a priori food pattern score (Mediterranean Adequacy Index: MAI) with long-term CHD mortality rates in the Seven Countries Study.Subjects/methods: Sixteen cohorts (12,763 men aged 40-59 years) were enrolled in the 1960s in seven countries (US, Finland, The Netherlands, Italy, Greece, former Yugoslavia: Croatia/Serbia, Japan). Dietary surveys were carried out at baseline and only in a subsample of each cohort. The average food consumption of each cohort was chemically analyzed for individual fatty acids and carbohydrates.Results: Ecologic correlations of diet were computed across cohorts for 50-year CHD mortality rates; 97% of men had died in cohorts with 50-year follow-up. CHD death rates ranged 6.7-fold among cohorts. At baseline, hard fat was greatest in northern Europe, olive oil in Greece, meat in the US, sweet products in northern Europe and the US, and fish in Japan. The MAI was high in Mediterranean and Japanese cohorts. The 50-year CHD mortality rates of the cohorts were closely positively ecologically correlated (r = 0.68-0.92) with average consumption of hard fat, sweet products, animal foods, saturated fat, and sucrose, but not with naturally occurring sugars. Vegetable foods, starch, and the a priori pattern MAI were inversely correlated (r = -0.59 to -0.91) with CHD mortality rates.Conclusions: Long-term CHD mortality rates had statistically significant ecologic correlations with several aspects of diet consumed in the 1960s, the traditional Mediterranean and Japanese patterns being rich in vegetable foods, and low in sweet products and animal foods. [ABSTRACT FROM AUTHOR]

Background: Controversy persists regarding the technical feasibility of laparoscopic total gastrectomy (LTG), and to our knowledge, no prospective study with a sample size sufficient to investigate its safety has been reported. We aimed to compare the postoperative morbidity and mortality rates in patients undergoing LTG and open total gastrectomy (OTG) for gastric cancer in prospectively enrolled cohort using nationwide web-based registry.Methods: From August 2014 to July 2015, consecutive patients undergoing LTG or OTG (925 and 1569 patients, respectively) at the participating institutions were enrolled prospectively into the National Clinical Database registration system. We constructed propensity score (PS) models separately in four facility yearly case-volume groups, and evaluated the postoperative morbidity and mortality in PS-matched 1024 patients undergoing LTG or OTG.Results: The incidence of overall morbidity were 84 (16.4%) in the OTG and 54 (10.3%) in the LTG groups (p = 0.01).The incidence of anastomotic leakage and pancreatic fistula grade B or above were not significantly different between the two groups (LTG 5.3% vs. OTG 6.1%, p = 0.59, LTG 2.7% vs. OTG 3.7%, p = 0.38, respectively). There were also no significant differences in the 30-day and in-hospital mortality rates between the two groups (LTG 0.2% vs. OTG 0.4%, p = 0.56; LTG 0.4% vs. OTG 0.4%, p = 1.00, respectively).Conclusion: The results from our nationally representative data analysis showed that LTG could be a safe procedure to treat gastric cancer compared to OTG. The indication for LTG should be considered carefully in a clinical setting. [ABSTRACT FROM AUTHOR]

Background: A nationwide survey was performed to clarify the recent status of acute liver failure (ALF) and late-onset hepatic failure (LOHF) in Japan.Methods: Two-step surveys for patients with ALF and LOHF meeting the Japanese diagnostic criteria were performed annually in 782 hospitals. The clinical features of the patients were then compared to those reported in previous surveys.Results: In total, 1554 and 49 patients with ALF and LOHF, respectively, who were seen between 2010 and 2015 were enrolled. The subjects were classified into 1280 patients with hepatitis (642 non-comatose and 638 comatose) and 323 patients without hepatitis (190 non-comatose and 133 comatose). Compared with patients seen between 1998 and 2009, an older patient age and a higher percentage of underlying extrahepatic disease were observed. Although hepatitis virus infection was the most frequent etiology, the percentage of patients with this etiology had decreased, compared with previous cohorts, while the percentages of patients with drug-induced liver injuries, autoimmune hepatitis, and an indeterminate etiology had increased. Liver transplantation was performed in 170 patients (10.6%), whereas artificial liver support with plasmapheresis and/or hemodiafiltration were performed for most of the comatose patients. The outcomes of comatose patients were unfavorable, similar to previous surveys, especially the outcomes of hepatitis B virus carriers, including those with de novo hepatitis B (survival rate of 5.4% without liver transplantation).Conclusion: Although the clinical features, including the etiologies, of patients with ALF and LOHF have changed, the outcomes of patients have not improved in recent years. [ABSTRACT FROM AUTHOR]

Background: Despite recent developments in surgical education, obstacles including inadequate budget, limited human resources, and a scarcity of time have limited its widespread adoption. To provide systematic training for laparoscopic inguinal hernia repair, we had previously developed and validated a checklist to evaluate the recorded performance of transabdominal preperitoneal (TAPP) repair. We had also developed an educational system that included didactic materials based on the TAPP checklist and incorporated remote evaluation and feedback system. The aim of this study was to evaluate the educational impact of the TAPP education system on novice surgeons.Methods: Residents and surgeons from participating hospitals, who had performed 0 or 1 TAPP procedure, were randomly assigned to the intervention group (IG), who trained using this new educational tool, and the control group (CG), who trained using the conventional system. Their surgical videos were rated by blinded raters. All participants performed their first case prior to randomization. The primary outcome was improvement of TAPP checklist score from the first to the third case.Results: Eighteen participants from 9 institutes were recruited for this study. Seven participants in the IG and 5 participants in the CG were included in the final analysis. The participants in the IG demonstrated significant improvement in their TAPP performance (p = 0.044) from their first case to their third case, whereas their counterparts in the CG failed to make any significant progress during the same period (p = 0.581).Conclusion: The new TAPP educational system was effective in improving the TAPP performance of novice surgeons. [ABSTRACT FROM AUTHOR]

Purpose: Favorable long-term outcomes of the Zilver PTX drug-eluting stent (DES) in femoropopliteal lesions have been demonstrated. Chronic renal failure (CRF) has been shown to be a risk factor for restenosis and decreased limb salvage. The results of the DES in patients with CRF have not previously been reported. This study compares the results with the DES in patients with CRF and those without CRF.Methods: This retrospective analysis from the Zilver PTX Japan Post-Market Surveillance Study included 321 patients with CRF and 584 patients without CRF. Outcomes included freedom from target lesion revascularization (TLR) and patency.Results: Of the patients included in this subgroup analysis, 2-year data were available for 209 patients in the CRF group and 453 patients in the non-CRF group. The two groups were similar in terms of lesion length and the frequency of in-stent restenosis. Critical limb ischemia, severe calcification, and diabetes were more common in patients with CRF, whereas total occlusion was more common in patients without CRF. Freedom from TLR rates were 81.4 versus 84.9% (p = 0.24), and patency rates were 70.7 versus 70.3% (p = 0.95) in patients with and without CRF at 2 years, respectively.Conclusion: This is the first comparative study of the DES in femoropopliteal artery lesions in patients with and without CRF. These results indicate that the DES placed in femoropopliteal artery lesions of CRF patients is safe and effective with similar patency and TLR rates to patients without CRF.Level Of Evidence: Level 3, Post-Market Surveillance Study. [ABSTRACT FROM AUTHOR]

The Japanese National Research Group on Idiopathic Bone Marrow Failure Syndromes has been conducting prospective registration, central review, and follow-up study for patients with aplastic anemia and myelodysplastic syndrome (MDS) since 2006. Using this database, we retrospectively analyzed the prognosis of patients with MDS. As of May 2016, 351 cases were registered in this database, 186 of which were eligible for the present study. Kaplan-Meier analysis showed that overall survival (OS) curves of the five risk categories stipulated by the revised international prognostic scoring system (IPSS-R) were reasonably separated. 2-year OS rates for the very low-, low-, intermediate-, high-, and very high-risk categories were 95, 89, 79, 35, and 12%, respectively. In the same categories, incidence of leukemic transformation at 2 years was 0, 10, 8, 56, and 40%, respectively. Multivariate analysis revealed that male sex, low platelet counts, increased blast percentage (>2%), and high-risk karyotype abnormalities were independent risk factors for poor OS. Based on these data, we classified Japanese MDS patients who were classified as intermediate-risk in IPSS-R, into the lower risk MDS category, highlighting the need for careful assessment of treatments within low- and high-risk treatment protocols. [ABSTRACT FROM AUTHOR]

Introduction: The superiority of tiotropium/olodaterol is demonstrated in improvement of lung function, dyspnea, lung hyperinflation, and quality of life compared with either monotherapy in patients with chronic obstructive pulmonary disease (COPD). Japanese Respiratory Society Guidelines for COPD management include improvement of exercise tolerance and daily physical activity as the treatment goals; however, there is limited evidence in Japanese patients with COPD.Methods: A protocol is developed for the VESUTO® study that investigates the efficacy of tiotropium/olodaterol fixed-dose combination (FDC) compared with tiotropium alone on inspiratory capacity (IC, volume from functional residual capacity to total lung capacity), exercise capacity, and daily physical activity in Japanese patients with COPD.Results: A total of 180 Japanese patients with COPD, aged ≥40 years will be enrolled into the double-blind, multicenter, active-controlled, crossover study (NCT02629965) and will be randomized to receive either tiotropium/olodaterol FDC or tiotropium for 6 weeks each [two puffs via RESPIMAT® (Boehringer Ingelheim, Ingelheim, Germany) inhaler in the morning]. The primary endpoint is IC at rest measured at 60 min post-dose after 6 weeks treatment. The secondary endpoints include the 6-min walk distance (6MWD) at 90 min post-dose and physical activity measured by the activity monitor in the last 2 weeks of the 6-week treatment periods. Lung function tests will also be assessed after 6 weeks treatment. A mixed-effects model repeated measures approach will be used for the primary and secondary endpoints.Conclusion: The VESUTO® study is the first randomized interventional study to investigate exercise capacity (6MWD) and physical activity measured by a 3-axis accelerometer in Japanese patients with COPD. The study could provide additional evidence of long-acting muscarinic antagonist (LAMA) + long-acting β2-agonist (LABA) combination therapy on patients' physical activities as well as lung function.Trial Registration: ClinicalTrials.gov: NCT02629965 (registered on December 1, 2015).Funding: The VESUTO study was funded by Nippon Boehringer Ingelheim Co., Ltd., Tokyo, Japan. [ABSTRACT FROM AUTHOR]

Purpose: We conducted a multi-institutional prospective study on accelerated partial breast irradiation (APBI) using interstitial brachytherapy. The clinical results over a minimum follow-up period of 30 months are presented here.Materials and Methods: Forty-six patients with breast cancer were treated with breast-conserving surgery and postoperative APBI. After confirmation of negative surgical margins and negative lymph nodes, a high-dose-rate brachytherapy protocol of 36 Gy/6 fractions was carried out. All clinical data were prospectively collected using the Common Terminology Criteria for Adverse Events ver. 3.0.Results: No recurrence was observed. Cumulative rates of grade 2 or higher late sequelae were 25% for fibrosis, 2% for fractures, 9% for pain, and 9% for soft tissue necrosis. Rates of excellent or good cosmetic results as assessed by the physician and patient were 93 and 89% at the 12-month follow-up and 76 and 74% at the 30-month follow-up, respectively. Large volumes of resected tissue in small breasts were associated with fibrosis of grade 2 or higher.Conclusion: APBI in Japanese women provides satisfactory clinical results except for cosmetic outcomes. There is some difficulty with the assessment of fibrosis and cosmetic outcomes, especially in patients with small breasts.Clinical Trial Registration Number: UMIN000001677. [ABSTRACT FROM AUTHOR]

Introduction: Most asthma patients have mild disease, although the burden of mild asthma is not well understood nor studied. Some evidence suggests that many patients with mild asthma experience suboptimal symptom control and exacerbations. This study characterizes the burden of illness and treatment patterns among patients with a confirmed diagnosis of mild asthma, defined as GINA Step 1 or Step 2, and residing in China, France, Germany, Italy, Japan, Spain, the United Kingdom, or the United States.Methods: The Respiratory Disease-Specific Programme prospective cross-sectional survey was conducted with primary care and specialty physicians in each of the eight countries. Physician and patient surveys assessed demographic and clinical characteristics, frequency and timing of asthma symptoms, exacerbations, and rescue inhaler usage, the most recent FEV1% predicted, and healthcare utilization. GINA Step was determined by prescribed treatment regimen. GINA Step 1 patients were prescribed as-needed reliever medication and Step 2 required treatment with a low-dose inhaled corticosteroid, leukotriene receptor antagonist, or theophylline. Treatment adherence was assessed with the Morisky Medication Adherence scale, disease control with the Asthma Control Test, and work and activity impairments with the Work Productivity and Activity Impairment scale.Results: The sample included 1115 GINA Step 1 and 2 patients, with 53% classified as Step 2. Overall asthma control was suboptimal, with reports of nocturnal symptoms (40.6%), symptom worsening (10.5%), and rescue inhaler usage in the last 4 weeks (33.6%). 25% of patients were uncontrolled. The overall mean number of exacerbations in the last 12 months was 0.4, with a higher frequency of exacerbations in Step 2 patients who also experienced more exacerbations requiring treatment intensification, an emergency department visit, or hospitalization.Conclusion: Mild asthma imposes a substantial burden on patients, establishing the need for comprehensive management plans and ongoing support for treatment adherence.Funding: AstraZeneca. [ABSTRACT FROM AUTHOR]

Objective: This Phase 2 study assessed the performance of positron emission tomography (PET) brain images made with Flutemetamol F 18 Injection in detecting β-amyloid neuritic plaques in Japanese subjects.Methods: Seventy subjects (25 with probable Alzheimer's disease (pAD), 20 with amnestic mild cognitive impairment (aMCI), and 25 cognitively normal healthy volunteers[HVs]) underwent PET brain imaging after intravenous Flutemetamol F 18 Injection (185 MBq). Images were interpreted as normal or abnormal for neuritic plaque density by each of five non-Japanese and five Japanese readers who were blinded to clinical data. The primary efficacy analysis (based on HV and pAD data) was the agreement of the non-Japanese readers' image interpretations with the clinical diagnosis, resulting in estimates of positive percent agreement (PPA; based on AD subjects; similar to sensitivity) and negative percent agreement (NPA; based on HVs; similar to specificity). Secondary analyses included PPA and NPA for the Japanese readers; inter-reader agreement (IRA); intra-reader reproducibility (IRR); quantitative image interpretations (standardized uptake value ratios [SUVRs]) by diagnostic subgroup; test-retest variability in five pAD subjects; and safety.Results: PPA was 92% for all non-Japanese readers and ranged from 88 to 92% for the Japanese readers. NPA ranged from 96 to 100% for both the non-Japanese readers and the Japanese readers. The majority image interpretations (the interpretations made independently by ≥3 of 5 readers) resulted in PPA values of 92 and 92% and NPA values of 100 and 96% for the non-Japanese and Japanese readers, respectively. IRA and IRR were strong. Composite SUVR values (mean of multiple regional values) allowed clear differentiation between pAD subjects and HVs. Test-retest variability ranged from 1.14 to 2.27%, and test-retest agreement of the blinded visual interpretations was 100% for all readers. Flutemetamol F 18 Injection was generally well tolerated.Conclusions: The detection of brain neuritic plaques in Japanese subjects using [18F]Flutemetamol PET images gave results highly consistent with clinical diagnosis, with non-Japanese and Japanese readers giving similar results. Inter-reader agreement and intra-reader reproducibility were high for both sets of readers. Visual delineation of abnormal and normal scans was corroborated by quantitative assessment, with low test-retest variability.Trial Registration: Clinicaltrials.gov registration number NCT02813070. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to investigate the clinical characteristics and practice pattern of patients with dry eye disease (DED) in eye clinics across Japan.Methods: A multi-center, cross-sectional study was conducted among patients with DED who visited eye clinics in Japan. Subjective symptoms, patient's background, ocular surface features, and tear function were evaluated. Main outcome measures were tear break-up time (TBUT), Schirmer I value, kerato-conjunctival staining score, and dry eye symptom questionnaire score.Results: Initially, 463 subjects were enrolled, and 449 cases (63 male and 386 female; mean age, 62.6 ± 15.7 years) were included in the final analysis. Overall, 94.9% of patients had a shortened TBUT (≤5 s), and 54.6% had an aqueous tear deficiency (Schirmer I value ≤5 mm). The most prevalent subtype of dry eye was aqueous-deficient dry eye, which was present in 35.0% of all patients, followed by short-BUT-type dry eye, which was seen in 26.7%.Conclusion: The two most common DED subtypes were aqueous-deficient and short-BUT-type dry eye. Shortened TBUT is the most common feature of dry eye, regardless of subtype. The current treatment choice mainly consisted of hyaluronic acid, two novel mucin secretagogues, diquafosol and rebamipide, and steroidal eye drops.Trial Registration: University Hospital Medical Information Network: UMIN (registries no. UMIN 000015890).Funding: Japan Dry Eye Society, Tokyo, Japan, and Santen Pharmaceutical Co., Ltd., Osaka, Japan. [ABSTRACT FROM AUTHOR]

Introduction: Sodium glucose co-transporter 2 (SGLT2) inhibitors exhibit diuretic activity, which is a possible mechanism underlying the cardiovascular benefit of these inhibitors. However, the osmotic diuresis-induced increase in urine volume, and the risk of dehydration have been of concern with SGLT2 inhibitor treatment. This study aimed to investigate the mechanism underlying SGLT2 inhibitor canagliflozin-induced diuresis in Japanese type 2 diabetes mellitus (T2DM) patients.Methods: Thirteen T2DM patients received a daily oral dose of 100 mg canagliflozin before breakfast for 6 days. Blood and urine samples were collected at predetermined time points. The primary endpoint was evaluation of correlations between changes from baseline in urine volume and factors that are known to affect urine volume and between actual urine volume and these factors.Results: Canagliflozin transiently increased urine volume and urinary sodium excretion on Day 1 with a return to baseline levels thereafter. Canagliflozin administration increased urinary glucose excretion, which was sustained during repeated-dose administration. Plasma atrial natriuretic peptide (ANP) and N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels decreased, while plasma renin activity increased. On Day 1 of treatment, changes in sodium and potassium excretion were closely correlated with changes in urine output. A post hoc multiple regression analysis showed changes in sodium excretion and water intake as factors that affected urine volume change at Day 1. Furthermore, relative to that at baseline, canagliflozin decreased blood glucose throughout the day and increased plasma total GLP-1 after breakfast.Conclusion: Canagliflozin induced transient sodium excretion and did not induce water intake at Day 1; hence, natriuresis rather than glucose-induced osmotic diuresis may be a major factor involved in the canagliflozin-induced transient increase in urine output. In addition, canagliflozin decreased plasma ANP and NT-proBNP levels and increased plasma renin activity, which may be a compensatory mechanism for sodium retention, leading to subsequent urine output recovery.Clinical Trial Registration: UMIN000019462.Funding: Mitsubishi Tanabe Pharma Corporation. [ABSTRACT FROM AUTHOR]

Purpose: To describe how we performed a protocol review, analyzed data, identified opportunities to reduce radiation exposure, and then implemented a new imaging protocol for non-contrast adult head CT at our institution with reduced radiation exposure, using the Japanese diagnostic reference levels (DRLs) as the reference.Methods: After analyzing the CT dose index (CTDIvol) and dose length product (DLP) in all non-contrast adult head CT examinations performed during a 3-month period (September to November 2015) in order to identify a specific protocol that contributed to the above-DRL-level radiation exposure observed for non-contrast adult head CT at our institution, phantom studies with objective and subjective image quality analyses were performed to develop a new imaging protocol. After implementing the new protocol, its feasibility was evaluated in terms of radiation exposure, prevalence of significant disease detection, and subjective image quality.Results: The review of 2040 examinations revealed that a helical protocol (CTDIvol = 93.4 mGy) with one of four CT scanners mainly contributed to the above-DRL-level radiation exposure (mean DLP at this scanner = 1401.2 mGy cm) in non-contrast adult head CT at our institution. To replace this protocol, the phantom study identified a wide-volume scan using 120 kVp, 350 mAs, a 4-cm detector, a slice thickness of 5 mm, and a CTDIvol of 69.8 mGy as a new protocol that yielded comparable image quality to the existing protocol. After the implementation of the new protocol, the overall mean DLP reduced to 1365 mGy cm without any apparent degradation of image quality. No significant decrease in the prevalence of significant findings after protocol revision was noted.Conclusion: We report the successful implementation of a new protocol with reduced radiation exposure for non-contrast head CT examinations. [ABSTRACT FROM AUTHOR]

Hypobaric hypoxic brain injury results in elevated peripheral S100B levels which may relate to blood-brain barrier (BBB) dysfunction. A period of acclimatisation or dexamethasone prevents altitude-related illnesses and this may involve attenuation of BBB compromise. We hypothesised that both treatments would diminish the S100B response (a measure of BBB dysfunction) on re-ascent to the hypobaric hypoxia of high altitude, in comparison to an identical ascent completed 48 h earlier by the same group. Twelve healthy volunteers, six of which were prescribed dexamethasone, ascended Mt Fuji (summit 3700 m) and serial plasma S100B levels measured. The S100B values reduced from a baseline 0.183 µg/l (95 % CI 0.083-0.283) to 0.145 µg/l (95 % CI 0.088-0.202) at high altitude for the dexamethasone group (n = 6) and from 0.147 µg/l (95 % CI 0.022-0.272) to 0.133 µg/l (95 % CI 0.085-0.182) for the non-treated group (n = 6) [not statistically significant (p = 0.43 and p = 0.82) for the treated and non-treated groups respectively]. [These results contrasted with the statistically significant increase during the first ascent, S100B increasing from 0.108 µg/l (95 % CI 0.092-0.125) to 0.216 µg/l (95 % CI 0.165-0.267) at high altitude]. In conclusion, an increase in plasma S100B was not observed in the second ascent and this may relate to the effect of acclimatisation (or hypoxic pre-conditioning) on the BBB. An exercise stimulated elevation of plasma S100B levels was also not observed during the second ascent. The small sample size and wide confidence intervals, however, precludes any statistically significant conclusions and a larger study would be required to confirm these findings. [ABSTRACT FROM AUTHOR]

Observational studies from national and international registries with large volumes of patients are commonly performed to identify superior strategies for hematopoietic stem cell transplantation. Major international and national stem cell transplant registries collect outcome data using electronic data capture systems, and a systematic study support process has been developed. Statistical support for studies is available from some major international registries, and international and national registries also mutually collaborate to promote stem cell transplant outcome studies and transplant-related activities. Transplant registries additionally take measures to improve data quality to further improve the quality of outcome studies by utilizing data capture systems and manual data management. Data auditing can potentially even further improve data quality; however, human and budgetary resources can be limiting factors in system construction and audits of the Japanese transplant registry are not currently performed. [ABSTRACT FROM AUTHOR]

Introduction: Although hyperlipidemia is a well known adverse event of atypical antipsychotic (AAP) medication, there are few studies that have quantitatively compared the risks of various AAPs.Objective: Our aim was to comparatively evaluate the risk of hyperlipidemia associated with the use of AAPs approved in Japan through a consecutive epidemiological study.Methods: We conducted a sequence symmetry analysis (SSA) using health insurance claims data to analyze the following nine AAPs approved for use in Japan: risperidone, paliperidone, perospirone hydrochloride hydrate, blonanserin, clozapine, olanzapine, quetiapine fumarate, aripiprazole, and zotepine. Exposed cases were identified from drug dispensing records as those who had been administered both AAPs and antihyperlipidemic drugs. The adjusted sequence ratio (ASR) and 95 % confidence interval (CI) for each individual AAP and for all AAPs were calculated while controlling for time trends in dispensing patterns.Results: Olanzapine was significantly associated with increased hyperlipidemia occurrence (ASR 1.56; 95 % CI 1.25-1.95). The ASRs obtained for risperidone (1.01; 95 % CI 0.80-1.27), perospirone hydrochloride hydrate (0.93; 95 % CI 0.63-1.39), blonanserin (0.83; 95 % CI 0.52-1.33), quetiapine fumarate (0.93; 95 % CI 0.73-1.18), and aripiprazole (1.02; 95 % CI 0.82-1.26) were approximately 1.0. Unstable estimates (wide CIs) were obtained for paliperidone and zotepine due to the small sample sizes.Conclusions: Among the AAPs used in Japan, only olanzapine was found to have an elevated risk of hyperlipidemia. In contrast, risperidone, perospirone hydrochloride hydrate, blonanserin, quetiapine fumarate, and aripiprazole had relatively low risks. [ABSTRACT FROM AUTHOR]

We comprehensively compared all available questionnaires for measuring quantitative autistic traits (QATs) in terms of reliability and construct validity in 3,147 non-clinical and 60 clinical subjects with normal intelligence. We examined four full-length forms, the Subthreshold Autism Trait Questionnaire (SATQ), the Broader Autism Phenotype Questionnaire, the Social Responsiveness Scale2-Adult Self report (SRS2-AS), and the Autism-Spectrum Quotient (AQ). The SRS2-AS and the AQ each had several short forms that we also examined, bringing the total to 11 forms. Though all QAT questionnaires showed acceptable levels of test-retest reliability, the AQ and SRS2-AS, including their short forms, exhibited poor internal consistency and discriminant validity, respectively. The SATQ excelled in terms of classical test theory and due to its short length. [ABSTRACT FROM AUTHOR]

We previously found that forest environments reduced stress hormones such as adrenaline and noradrenaline and showed the relaxing effect both in male and female subjects. In the present study, we investigated the effects of walking under forest environments on cardiovascular and metabolic parameters. Sixteen healthy male subjects (mean age 57.4 ± 11.6 years) were selected after obtaining informed consent. The subjects took day trips to a forest park in the suburbs of Tokyo and to an urban area of Tokyo as a control in September 2010. On both trips, they walked for 2 h in the morning and afternoon on a Sunday. Blood and urine were sampled on the morning before each trip and after each trip. Blood pressure was measured on the morning (0800) before each trip, at noon (1300), in the afternoon (1600) during each trip, and on the morning (0800) after each trip. The day trip to the forest park significantly reduced blood pressure and urinary noradrenaline and dopamine levels and significantly increased serum adiponectin and dehydroepiandrosterone sulfate (DHEA-S) levels. Walking exercise also reduced the levels of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and urinary dopamine. Taken together, habitual walking in forest environments may lower blood pressure by reducing sympathetic nerve activity and have beneficial effects on blood adiponectin and DHEA-S levels, and habitual walking exercise may have beneficial effects on blood NT-proBNP levels. [ABSTRACT FROM AUTHOR]

Background: Acid suppression induced by rabeprazole 5 mg in patients with NERD has not been reported in the literature.Aims: The objective of this study was to investigate gastroesophageal acid suppression in NERD patients by rabeprazole 5 mg and 10 mg/day.Methods: Subjects were grade M (minimal changes) NERD patients. Twenty-two patients not responding to open label antacid therapy entered a double-blind treatment phase in which rabeprazole 5 mg or 10 mg/day for four weeks were compared. Twenty-four-hour esophageal pH monitoring was performed before and on treatment (at week 4) to assess the pharmacodynamic effect of these doses of rabeprazole.Results: The frequency of heartburn episodes and the number of acid reflux episodes in the esophagus corresponded well in grade M NERD patients (r=0.44, P=0.042). Median percentage of time at pH<4 was 4.3% before treatment and 1.1% on treatment with rabeprazole 5 mg (change from baseline; -2.5%), whereas the median percentage of time at pH<4 in the rabeprazole 10 mg group was 7.4% before treatment and 0.5% on treatment (change from baseline; -6.6%). Likewise, treatment-related changes of median number of reflux episodes were -18.0 with rabeprazole 5 mg and -44.0 with rabeprazole 10 mg. For each esophageal pH data, no significant differences were observed between the two groups (P=0.377, P=0.077).Conclusions: Administration of 5 mg and 10 mg rabeprazole sufficiently inhibited pathological gastroesophageal acid reflux and relieved heartburn episodes in NERD patients who did not respond to an antacid. Further investigation would be necessary to determine proper usage of the two doses. [ABSTRACT FROM AUTHOR]

Objective: To investigate how birthplace influences the incidence of papillary thyroid cancer among Asian American women.Methods: Birthplace- and ethnic-specific age-adjusted and age-specific incidence rates were calculated using data from the California Cancer Registry for the period 1988-2004. Birthplace was statistically imputed for 30% of cases using a validated imputation method based on age at Social Security number issuance. Population estimates were obtained from the US Census. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were estimated for foreign-born vs. US-born women.Results: Age-adjusted incidence rates of papillary thyroid cancer among Filipina (13.7 per 100,000) and Vietnamese (12.7) women were more than double those of Japanese women (6.2). US-born Chinese (IRR = 0.48, 95% CI: 0.40-0.59) and Filipina women (IRR = 0.74, 95% CI: 0.58-0.96) had significantly higher rates than those who were foreign-born; the opposite was observed for Japanese women (IRR = 1.55, 95% CI: 1.17-2.08). The age-specific patterns among all foreign-born Asian women and US-born Japanese women showed a slow steady increase in incidence until age 70. However, among US-born Asian women (except Japanese), substantially elevated incidence rates during the reproductive and menopausal years were evident.Conclusions: Ethnic- and birthplace-variation in papillary thyroid cancer incidence can provide insight into the etiology of this increasingly common and understudied cancer. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the associations between hsMAD2 mRNA expression in tumor cells and sensitivity to paclitaxel or patient prognosis in neuroblastoma.Methods: Fifty-one formalin-fixed paraffin-embedded tumor samples were manually microdissected to collect tumor cells, and RNA was purified. Nineteen clinical samples of advanced neuroblastoma showed appropriate quality of the isolated RNA for real-time reverse transcription-polymerase chain reaction (RT-PCR) analyses. The hsMAD2 expression levels were determined by real-time RT-PCR in 4 neuroblastoma cell lines and 19 clinical samples. The sensitivity to paclitaxel was assessed by WST-8 colorimetric assays and flow cytometry. HsMAD2 expression of the clinical samples was investigated for its association with prognosis in advanced neuroblastoma patients.Results: There was a significant positive correlation between hsMAD2 mRNA expression and the sensitivity to paclitaxel in four neuroblastoma cell lines. High hsMAD2 expression may be correlated with paclitaxel-induced apoptosis. Kaplan-Meier survival curves were stratified by hsMAD2 expression using the median value as a cut-off point and analyzed for prognostic significance by the log-rank test (P = 0.0467). Furthermore, multivariate survival analysis revealed that only hsMAD2 expression had a significant impact on the overall survival rate.Conclusions: Our results may warrant clinical application of paclitaxel in neuroblastoma treatment for poor prognosis patients. [ABSTRACT FROM AUTHOR]

The aim of osteoporosis treatment is to prevent future fractures. Although concurrent treatment has been used very frequently for osteoporosis in clinical practice, there are no data on accurate and verified effectiveness of concurrent treatment for fracture prevention in patients with osteoporosis. To clarify the clinical usefulness of concurrent treatment, the Japan Osteoporosis Society has authorized the establishment of the A-TOP (Adequate Treatment of Osteoporosis) research group. The objective of this research is to establish a design for a clinical trial to prove whether concurrent treatment using both alfacalcidol (1-alpha-hydroxycholecalciferol) and alendronate is more effective as compared to treatment using alendronate alone in terms of fracture prevention. The present study was named JOINT (Japanese Osteoporosis Intervention Trial) and is based on a method using national, prospective, randomized, open-labeled, blinded endpoints focusing on postmenopausal osteoporosis with a high risk for fracture. The patients were mainly selected by practitioners and allocated randomly by a central registration system into two groups, of which one received 5 mg/day of alendronate alone, and the other received 1 μg/day of 1-alpha-hydroxycholecalciferol (alfacalcidol) in addition to the alendronate. The endpoints focused primarily on fracture prevention, and the patients' quality of life (QOL) and change in body height, as well as adherence and the adverse events of the treatments were evaluated secondarily. To obtain sufficient statistical power in the events during a 2-year observation period, the patients who are expected to have higher risk were selected to participate in this study, and it was decided that the final plan would involve 890 patients per group (two-sided alpha = 0.05, power = 0.8). Data collection began in November 2003. Correspondence regarding the registration of the investigator and the progress of the study was conducted through a web system from the Public Health Research Foundation to practitioners. [ABSTRACT FROM AUTHOR]

Background and Objective: Clinical characteristics of human bocavirus (HBoV) infection have been studied worldwide, but their importance of those characteristics remains unknown. We investigated distinctive clinical features of HBoV-positive children with lower respiratory tract infection (LRTI).Methods and Results: During April 2007-July 2009, for 402 hospitalized children younger than 2 years with LRTI, we prospectively examined virus genomes in nasopharyngeal swabs for HBoV, respiratory syncytial virus (RSV), rhinovirus, metapneumovirus, parainfluenzavirus, and adenovirus. The HBoV genomes were identified in 34 patients (8.5%). Clinical and laboratory data of HBoV-positive and other virus/bacteria-negative patients (n = 18) were analyzed and compared with data of RSV-single positive patients (n = 99). The seasonal distribution of HBoV exhibits a concentration of cases during March-September, with most RSV cases occurring during winter in Japan. The minimum age of HBoV-positive patients was 5 months, although 44 patients (44%) with RSV were younger than 6 months. The main clinical features were respiratory distress and hypoxia. Hypoxia advances within 3 days after onset. The mean oxygen saturation on arrival was 92.8%, which was significantly lower than that in patients with RSV (p < 0.001). White blood cell counts were similar among groups. However, the percentage of neutrophils in white blood cells were significantly higher in HBoV-positive patients (62 vs. 45%, p < 0.001). Their prognoses were good. Their hospital stays were 6.6 days.Conclusions: HBoV-single positive patients show several clinical characteristics, such as seasonality, age, hypoxia, and neutrophilia, which differ from those with RSV infection. [ABSTRACT FROM AUTHOR]

To prevent falls in Japan, both gait and resistance training of the lower extremities are recommended. However, resistance training for the elderly induces muscle damage. Recently, aquatic exercise using water buoyancy and resistance have commonly been performed by the elderly. We have now produced new water-resistance equipment. The purpose of the present study was to evaluate the efficacy of aquatic exercise training using the new equipment for the elderly. Subjects were divided into two groups: a resistance group of 12 subjects (using water-resistance equipment) and a non-resistance group of eight subjects (without the equipment). The aquatic exercise training was 90 min, three times per week for 8 weeks, and mostly consisted of walking. All subjects underwent anthropometric measurements, physical performance testing, and profile of mood states (POMS). Significant improvements were observed in muscle strength in plantar flexion, and the timed up and go test (TUG) in both groups. Additionally, 10-m obstacle walking and 5-m maximum walking speed and length with eye-open were significantly improved in the resistance group. Also, a low negative correlation was found between the degree of change in TUG and POMS (tension and anxiety) scores in the resistance group. As it became easier to maintain posture, stand, and move, tension and anxiety in everyday life were alleviated with improvement of strength of the lower extremities and balance function. The present aquatic exercise training using water-resistance equipment may be used by the elderly to improve balance and walking ability, which are associated with the prevention of falls. [ABSTRACT FROM AUTHOR]

Human Bocavirus (HBoV) as a newly discovered parvovirus has been commonly detected in respiratory tract infections. However, its role in acute otitis media (AOM) has not been well studied. We examined HBoV in Japanese children with AOM and evaluated the virus prevalence together with clinical manifestations and bacterial findings. Overall, 222 nasopharyngeal swabs and 176 middle ear fluids (MEF) samples were collected from 222 children with AOM (median age, 19 months) between May 2006 and April 2007. HBoV detection was performed by PCR and bacterial isolation by standard culture methods. HBoV was found in the nasopharyngeal aspirates of 14 children (6.3%) and in the MEF of six children (2.7%). When HBoV detection results were evaluated with clinical characteristics of children, resolution time of AOM was significantly longer (p=0.04), and rate of fever symptom was also higher in HBoV-positive group (p=0.04). Furthermore, we found positive correlation between detection of HBoV and Streptococcus pneumoniae in the MEF (p=0.004). Nevertheless, nasopharyngeal proportion of S. pneumoniae was similar between virus positive and negative groups. Furthermore, S. pneumoniae was detected as a single pathogen in all MEF of HBoV-positive cases but one, while it presents mixed with other pathogenic bacteria in nasopharynx. In conclusion, HBoV may worsen the clinical symptoms and prolong the clinical outcome of AOM in pediatric population. Finally, HBoV may prime the secondary bacterial infection in the middle ear in favor of S. pneumoniae. [ABSTRACT FROM AUTHOR]

A nationwide survey was conducted for identifying ataxia-telangiectasia (AT) patients in Japan. Eighty-nine patients were diagnosed between 1971 and 2006. Detailed clinical and laboratory data of 64 patients including affected siblings were collected. Analyses focused on malignancy, therapy-related toxicity, infection, and hematological/immunological parameters. The phenotypic variability of AT was assessed by comparing 26 affected siblings from 13 families. Malignancy developed in 22% of the cases and was associated with a high rate of severe therapy-related complications: chemotherapy-related cardiac toxicity in 2 children, and severe hemorrhagic cystitis requiring surgery in 2 patients. The frequency of serious viral infections correlated with the T cell count. Hypogammaglobulinemia with hyper-IgM (HIGM) was recorded in 5 patients, and 3 patients developed panhypogammaglobulinemia. Differences in immunological parameters were noted in siblings. Four patients showed an HIGM phenotype, in contrast to their siblings with normal IgG and IgM levels. The patients with HIGM phenotype showed reduced levels of TRECs and CD27+CD20+ memory B cells. The findings suggest that hitherto unidentified modifier genes or exogenous environmental factors can influence the overall immune responses. Our data along with future prospective study will lead to better understanding of the hematological/immunological phenotypes and to better care of the patients. [ABSTRACT FROM AUTHOR]

The primary objective of this study was to investigate the tolerability, efficacy and pharmacokinetic profile of gemtuzumab ozogamicin (GO) in patients with relapsed and/or refractory CD33-positive acute myeloid leukemia (AML). Patients received 2-h infusions of GO twice with an interval of approximately 14 days. Tolerability was assessed using the National Cancer Institute Common Toxicity Criteria Version 2.0. Samples for pharmacokinetics were taken on day 1 and day 8 of the first treatment cycle. The dose was increased stepwise and, in each cohort, patients were treated at the same dose. Forty patients, median age 58 years (range 28-68) were treated; 20 and 20 patients were enrolled to the phase I and II parts, respectively. In the phase I part, dose-limiting toxicities (DLTs) were hepatotoxicities, and the recommended dose was established as 9 mg/m2 given as two intravenous infusions separated by approximately 14 days. The pharmacokinetic study revealed that Cmax and AUC were equivalent to those of non-Japanese patients. In the phase II part, complete remission was observed in 5 patients, and one patient had complete remission without platelet recovery. Four of these 6 in remission and one in the phase I are long-term survivors (alive for at least 44 months). GO is safe and effective as a single agent among Japanese CD33-positive AML patients. Remission lasted longer in a subset of patients than in non-Japanese patients in earlier studies. Further studies of this agent are warranted to establish standard therapy. [ABSTRACT FROM AUTHOR]