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Pericardial effusion (PE) presentation varies from an incidental finding to a life-threatening situation; thus, its etiology and clinical course remain unknown. The aim of the present study was to retrospectively investigate these factors.We analyzed 171 patients (0.4%) who presented with PE among 34,873 patients who underwent echocardiography between 2011 and 2021 at our hospital. Clinical and prognostic information was retrieved from electronic medical records. The primary endpoints were all-cause death, hospitalization due to heart failure (HF), and other cardiovascular events such as cardiovascular death, acute coronary syndrome, elective percutaneous coronary intervention, and stroke.The etiologies of PE were as follows: idiopathic (32%), HF-related (18%), iatrogenic (11%), cardiac surgery-related (10%), radiation therapy-related (9%), malignancy (8%), pericarditis/myocarditis (8%), myocardial infarction-related (2%), and acute aortic dissection (2%). Patients with idiopathic/HF etiology were more likely to be older than the others.During a mean follow-up period of 2.5 years, all-cause death occurred in 21 patients (12.3%), cardiovascular events in 10 patients (5.8%), and hospitalization for HF in 24 patients (14.0%). All-cause death was frequently observed in patients with malignancy (44% per person-year). Cardiovascular events were mostly observed in patients with radiation therapy-related and malignancy (8.6% and 7.3% per person-year, respectively).The annual incidence of hospitalization for HF was the highest in patients with HF-related (25.1% per person-year), followed by radiation therapy-related (10.4% per person-year).This retrospective study is the first, to the best of our knowledge, to reveal the contemporary prevalence of PE, its cause, and outcome in patients who visited a cardiovascular hospital in an urban area of Japan.

The eye lens is responsible for focusing objects at various distances onto the retina and its refractive power is determined by its surface curvature as well as its internal gradient refractive index (GRIN). The lens continues to grow with age resulting in changes to the shape and to the GRIN profile. The present study aims to investigate how the ageing process may influence lens optical development. Murine lenses of accelerated senescence-prone strain (SAMP8) aged from 4 to 50 weeks; senescence-resistant strain (SAMR1) aged from 5 to 52 weeks as well as AKR strain (served as control) aged from 6 to 70 weeks were measured using the X-ray interferometer at the SPring-8 synchrotron Japan within three consecutive years from 2020 to 2022. Three dimensional distributions of the lens GRIN were reconstructed using the measured data and the lens shapes were determined using image segmentation in MatLab. Variations in the parameters describing the lens shape and the GRIN profile with age were compared amongst three mouse strains. With advancing age, both the lens anterior and posterior surface flattens and the lens sagittal thickness increase in all three mouse strains (Anterior radius of curvature increase at 0.008 mm/week, 0.007 mm/week and 0.002 mm/week while posterior radius of curvature increase at 0.002 mm/week, 0.007 mm/week and 0.003 mm/week respectively in AKR, SAMP8 and SAMR1 lenses). Compared with the AKR strain, the SAMP8 samples demonstrate a higher rate of increase in the posterior curvature radius (0.007 mm/week) and the thickness (0.015 mm/week), whilst the SAMR1 samples show slower increases in the anterior curvature radius (0.002 mm/week) and its thickness (0.013 mm/week). There are similar age-related trends in GRIN shape in the radial direction (in all three types of murine lenses nr2 and nr6 increase with age while nr4 decrease with age consistently) but not in the axial direction amongst three mouse strains (nz1 of AKR lens decrease while of SAMP8 and SAMR1 increase with age; nz2 of all three models increase with age; nz3 of AKR lens increase while of SAMP8 and SAMR1 decrease with age). The ageing process can influence the speed of lens shape change and affect the GRIN profile mainly in the axial direction, contributing to an accelerated decline rate of the optical power in the senescence-prone strain (3.5 D/week compared to 2.3 D/week in the AKR control model) but a retardatory decrease in the senescence-resistant strain (2.1 D/week compared to the 2.3D/week in the AKR control model)., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: In children in a metropolitan area of Tokyo, Japan, behavioral change and influenza infection associated with the frequency of nonpharmaceutical interventions (NPI) was assessed from the 2018-2019 season (Preseason) and the 2020-2021 season (coronavirus disease 2019 [COVID-19] season)., Methods: We conducted an exclusive survey among children attending preschool, elementary school, and junior high school in the Toda and Warabi regions, Japan, during the 2018-2019 (Preseason, distributed via mail) and 2020-2021 seasons (COVID-19 season, conducted online). The proportion of preventive activities (hand washing, face mask-wearing, and vaccination) was compared in the Preseason with that of the COVID-19 season. The multivariate logistic regression model was further applied to calculate the adjusted odds ratio (AOR) with 95% confidence intervals (CIs) for influenza infection associated with NPI frequency (hand washing and face mask wearing) in each Preseason and COVID-19 season., Results: The proportion of vaccinated children who carried out hand washing and face mask wearing was remarkably higher during the COVID-19 season (48.8%) than in the Preseason (18.2%). A significant influenza infection reduction was observed among children who washed hands and wore face masks simultaneously (AOR, 0.87; 95% CI, 0.76-0.99; P = 0.033)., Conclusions: A strong interest and performance in the intensive measures for the prevention of influenza under the COVID-19 pandemic was demonstrated. Positive association was observed from a combination of NPI, hand washing, and face mask-wearing and influenza infection. This study's findings could help in activities or preventive measures against influenza and other communicable diseases in children., (© 2023. The Author(s).)

This study investigated nurses' and patients' perceptions of hospital room environment and patient pajama design. Nurses working in a Japanese university hospital and patients aged 20 and older were surveyed. Over 75% of patients rated the hospital environment and hospital rooms as "very good" or "good," but less than one in three nurses rated them similarly. Patients were more likely than nurses to rate rental pajamas as "very good" or "good." Contrary to the nurses, only about one in four patients valued wearing well-designed pajamas. Nurses' and patients' perceptions differed regarding hospital pajamas, but not about improving hospital rooms.

Objective: We described the characteristics of children reported as having influenza across five consecutive influenza seasons and investigated the usefulness of setting influenza thresholds in two satellite cities of Tokyo, Japan., Methods: An annual survey was conducted among parents of children at preschools (kindergartens and nursery schools), elementary schools and junior high schools in Toda and Warabi cities, Saitama prefecture, at the end of the 2014-2018 influenza seasons. Using the World Health Organization method, we established seasonal, high and alert thresholds., Results: There were 64 586 children included in the analysis. Over the five seasons, between 19.1% and 22% of children annually were reported as having tested positive for influenza. Influenza type A was reported as the dominant type, although type B was also reported in more than 40% of cases in the 2015 and 2017 seasons. The median period of the seasonal peak was 3 weeks in mid-January, regardless of school level. Of the five surveyed seasons, the high threshold was reached in 2014 and 2018, with no season exceeding the alert threshold., Discussion: This study provides insights into the circulation of influenza in children in the study areas of Toda and Warabi, Japan, from 2014 to 2018. Although we were able to utilize these annual surveys to calculate influenza thresholds from five consecutive seasons, the prospective usefulness of these thresholds is limited as the survey is conducted at the end of the influenza season., ((c) 2022 The authors; licensee World Health Organization.)

Influenza vaccination is recommended for children. In particular, those aged 6 months to 12 years were recommended two vaccinations in Japan, whereas the recommended year range for the twice vaccination is 6 months to 8 years by the World Health Organization (WHO). This study assessed the effectiveness of influenza vaccination and whether the twice vaccinations enhanced preventive effects against influenza infection among children living in two satellite cities of a metropolitan area in Tokyo, Japan. During the influenza season of 2014-2018, parents of all preschool, elementary school, and junior high school children participated in an annual survey. Adjusted odds ratios (AOR) with 95% confidence intervals (CIs) were calculated via multivariate logistic regression analysis to evaluate influenza vaccination effectiveness and trends in the number of vaccinations. Among the 108,362 children who received the research questionnaire, 76,753 (70.8%) responded. After excluding responses without basic information, 64,586 children were included in the analysis. Vaccination was more effective in preschool and lower grade elementary school children given the increase in the number of vaccinations (test for trend: P < 0.001). The AOR of influenza for pre, grade 1 elementary, and grade 2 schoolchildren who received two vaccinations was 0.63 (95% CI, 0.59-0.69), 0.75 (0.67-0.83), and 0.81 (0.71-0.92), respectively, when compared to those without vaccination. However, no trend in vaccinations and their effectiveness was observed in the third and higher-grade school children. Our findings support the recommendation by the WHO, and could help guide influenza vaccination policies for children in Japan.

Glasgow prognostic score (GPS) has been used to evaluate inflammatory response and nutritional status. This study aimed to investigate the impact of nutritional status on cardiac prognosis by using GPS in patients after undergoing percutaneous coronary intervention (PCI). We included 862 patients who underwent PCI for stable angina pectoris between 2015 and 2018. We used the original cutoff values, which were an albumin (Alb) level of 3.5 g/dl and a C-reactive protein (CRP) level of 0.3 mg/dl. We categorized them into the three groups: originally defined GPS (od-GPS) 0 (high Alb and low CRP), 1 (low Alb or high CRP), and 2 (low Alb and high CRP). Major adverse clinical events (MACEs) included all-cause death, nonfatal myocardial infarction, revascularization, and hospitalization for heart failure. The median follow-up period was 398.5 days. During the follow-up, MACEs occurred in 136 patients. Od-GPS 2 had higher prevalence rates in terms of chronic kidney disease (CKD; 31.7% [229/722] vs. 44.9% [53/118] vs. 63.6% [14/22], p < 0.001), hemodialysis (6.4% [46/722] vs. 14.4% [17/118] vs. 31.8% [7/22], p < 0.001), and heart failure cases (HF; 9.1% [66/722] vs. 14.4% [17/118] vs. 27.3% [6/22], p = 0.007), with higher creatinine (1.17 ± 1.37 mg/dl vs. 1.89 ± 2.60 mg/dl vs. 3.49 ± 4.01 mg/dl, p < 0.001) and brain natriuretic peptide levels (104.1 ± 304.6 pg/ml vs. 242.4 ± 565.9 pg/ml vs. 668.1 ± 872.2 pg/ml, p < 0.001) and lower low-density lipoprotein cholesterol (101.5 ± 32.9 mg/dl vs. 98.2 ± 28.8 mg/dl vs. 77.1 ± 24.3 mg/dl, p = 0.002) than od-GPS 0 and 1.Od-GPS 2 (HR 2.42; 95% CI 1.16-5.02; p = 0.018), od-GPS 1 (HR 2.09; 95% CI 1.40-3.13; p < 0.001), diabetes (HR 1.41; 95% CI 1.00-1.99; p = 0.048), CKD (HR 2.10; 95% CI 1.49-2.96; p < 0.001), and HF (HR 1.64; 95% CI 1.05-2.56; p = 0.029) were independent predictors of MACEs. A scoring system using CRP and Alb levels with a milder definition than GPS suitably predicted the risk of MACEs in the patients who underwent PCI., (© 2021. Springer Japan KK, part of Springer Nature.)

Introduction: We investigated trends in the proportion of diabetes treatment and glycemic control, which may be altered by recent advances in insulin and non-insulin drugs, in Japanese patients with type 2 diabetes., Research Design and Methods: A serial cross-sectional study was performed using a multicenter large-population database from the Japan Diabetes Clinical Data Management study group. Patients with type 2 diabetes who attended clinics belonging to the study group between 2002 and 2018 were included to examine trends in glycated hemoglobin A1c (HbA1c) by treatment group using multivariable non-linear regression model., Results: The proportion of patients with insulin only decreased from 15.0% to 3.6%, patients with insulin+non-insulin drugs increased from 8.1% to 15.1%, patients with non-insulin drugs increased from 50.8% to 67.0%, and those with no drugs decreased from 26.1% to 14.4% from 2002 to 2018, respectively. The HbA1c levels of each group, except for no drugs, continued to decrease until 2014 (unadjusted mean HbA1c (%) from 2002 to 2014: from 7.89 to 7.45 for insulin only, from 8.09 to 7.63 for insulin+non-insulin, and from 7.51 to 6.98 for non-insulin) and remained unchanged thereafter. Among insulin-treated patients, use of human insulin decreased, use of long-acting analog insulin increased, and concomitant use of non-insulin drugs increased (from 35.1% in 2002 to 80.9% in 2018), which included increased use of dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide 1 receptor agonists, and the persistently high use of metformin., Conclusions: During the past two decades, combined use of insulin and non-insulin drugs increased and glycemic control improved and leveled off after 2014 in Japanese patients with type 2 diabetes. Further studies of the trend in association with age and factors related to metabolic syndrome are necessary to investigate strategies aiming at personalized medicine in diabetes care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims/introduction: Type 2 diabetes mellitus is caused by a relative imbalance between insulin secretion and sensitivity related to the body mass index (BMI). Seven categories of oral antidiabetic drugs (OADs) are available in Japan. It is important to assess the OAD utilization patterns based on patients' BMI levels., Materials and Methods: OAD prescribing patterns from 2002 to 2019 were analyzed using the data collected in the computerized diabetes care database provided by the Japan Diabetes Clinical Data Management Study Group; OAD utilization patterns in 25,751 OAD-treated type 2 diabetes mellitus patients registered in 2019 were analyzed after classifying them into five categories of BMI., Results: Comparing OAD usage between 2002 and 2019, sulfonylureas decreased from 44.5 to 23.2%, and biguanides (BGs) increased from 19.3 to 50.3%. Dipeptidyl peptidase-4 inhibitors (DPP4is) increased to 56.9% in 2019. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) increased to 23.6% in 2019. About 90% of type 2 diabetes mellitus patients had BMI < 30 kg/m 2 . DPP4is were the most used OADs in 2019. When BMI exceeded 30 kg/m 2 , use of BGs and sodium-glucose cotransporter 2 inhibitors increased, and use of sulfonylureas and DPP4is decreased. Although DPP4is were the most used OADs for patients with BMI <30 kg/m 2 , they were the third most prescribed OADs for patients with BMI >35 kg/m 2 after BGs and sodium-glucose cotransporter 2 inhibitors ., Conclusions: DPP4i usage was as high as that of BG in the analysis of Japanese type 2 diabetes mellitus patients with relatively low BMI. This was considered to be a treatment option appropriate for the pathophysiology in Japanese patients., (© 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Catheter ablation for atrial fibrillation (AF) has been an established and frequently utilized approach in a variety of clinical settings. Nevertheless, real-world data about the clinical course of AF patients after initial catheter ablation remain limited, and these are mainly derived from particular registries or selected high-volume centers.In this study, we used health check-ups and insurance claims database from a Japanese insurance organization. The study population was comprised of 1777 patients who underwent catheter ablation for AF before June 2016. During the 3-year follow-up period, 396 (22.3%) patients underwent at least one repeated AF ablation, while 74 (4.2%) underwent two or more repeated ablations. In multivariate Cox regression analysis, longer time after AF diagnosis (7-11 months and ≥12 months versus 1-6 months) (HR, 1.05; 95% CI, 1.01-1.08 and HR, 1.04; 95% CI 1.02-1.07) was independently associated with repeated ablation. The discontinuation rates of OACs and AADs after the first ablation were 26.7% and 63.0% at 3 months and 75.2% and 89.1% at 1 year after the initial ablation, respectively. The former was independently associated with shorter time after AF diagnosis and lower diastolic blood pressure, whereas the latter was independently associated with older age, smaller CHADS 2 score, and shorter time after AF diagnosis.We presented real-world data regarding the clinical course of young Japanese AF patients after initial catheter ablation based on a claims database in Japan.

Background: Direct oral anticoagulants (DOACs) are widely used for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). We investigated the adherence of DOACs for years known to be associated with the effectiveness in Japanese NVAF patients, using a claim database., Method: We performed a retrospective evaluation of NVAF patients in a claims database in Japan, who initiated dabigatran, rivaroxaban, and apixaban between April 2011 and June 2016. Drug persistence was assessed by Kaplan-Meier method for the initially-prescribed DOAC and all DOACs including switched ones. Proportion of days covered (PDC) was also evaluated in patients with persistent prescription and compared among DOACs., Results: In the total of 671 patients, rivaroxaban (47%) was more prescribed than dabigatran (28%) and apixaban (25%). Drug persistence at 3 years was higher in rivaroxaban (69%) than dabigatran (57%) and apixaban (67%). Including switching to other DOACs, persistence of DOACs was 72% at 3 years without significant differences between index-DOACs. In multivariate Cox regression analysis, absence of hypertension, and prior history of cancer were significantly associated with the drug discontinuation of all DOACs. The mean PDC was ~ 95% and the frequency of high-adherent patients (PDC ≥0.80) was more than 90%, which similarly persisted at 3 years and showed no significant differences between index DOACs., Conclusion: In a real-world Japanese claim data analysis, about 70% of patients under DOAC showed persistence with anticoagulation therapy at 3 years. High adherence to DOACs assessed by PDC (over 90%) persisted to 3 years regardless of the types of DOACs., Competing Interests: Declaration of Competing Interest Dr Suzuki received research fund from Daiichi Sankyo and Mitsubishi Tanabe Pharm and lecture fees from Daiichi Sankyo and Bristol-Myers Squibb. Dr Yamashita has received research funds and/or lecture fees from Daiichi Sankyo, Bayer Yakuhin, Bristol-Myers Squibb, Pfizer, Ono Pharmaceutical, and Toa Eiyo., (Copyright © 2021. Published by Elsevier Ltd.)

Aims: To evaluate the safety, pharmacokinetics and pharmacodynamics of BI 655064 in healthy Chinese and Japanese subjects after administration of single doses of 80-240 mg and multiple dosing of 240 mg once weekly over 4 weeks., Methods: Two phase 1, double-blind, placebo-controlled studies were conducted (single-rising doses of BI 655064 in Chinese/Japanese male subjects [n = 12 per BI 655064 dose group] or repeated 240 mg BI 655064 in Chinese male subjects [n = 9]). Plasma samples were collected to investigate BI 655064 pharmacokinetics, pharmacodynamics (CD40 receptor occupancy [RO]) and immunogenicity, along with the safety and tolerability of BI 655064., Results: BI 655064 showed good overall tolerability following single-dose administration of 80-240 mg and repeated administration of 240 mg BI 655064 over 4 weeks. More Chinese subjects reported adverse events compared with Japanese subjects following single-dose administration (59.4% vs 3.1%). BI 655064 exhibited nonlinear, saturable kinetics, with higher doses resulting in slower apparent clearance (0.514-0.713 mL min -1 ), and disproportionately higher total exposure (AUC 0-inf ; 5610-7780 μg·h mL -1 ) and maximum plasma concentration (15 700-21 300 ng mL -1 ) with 240 mg BI 655064. Ninety percent inhibition of CD40 RO was achieved with doses ≥120 mg, and a direct relationship between BI 655064 plasma concentration and inhibition of CD40 RO was observed. Most subjects had a positive treatment-emergent antidrug antibody response., Conclusions: BI 655064 pharmacokinetic and safety profiles in East Asian male subjects were consistent with those observed in a Western population. No adjustments in the BI 655064 dosing recommendations are warranted for future clinical trials., (© 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Continuous-flow left ventricular assist device (CF-LVAD) substantially improves survival in endstage heart failure patients. However, bleeding complications are common after CF-LVAD implantation and in some cases, re-exploration for bleeding is needed. We aimed to investigate the incidence, timing, and risk factors of bleeding requiring re-exploration after CF-LVAD implantation., Methods and results: We retrospectively reviewed 162 consecutive patients (age 43±13 years, 71% men) who underwent CF-LVAD implantation (HeartMateII 119, Jarvik2000 15, HVAD 13, EVAHEART 10, DuraHeart 5) from January 2012 to June 2019. During follow-up [median 662 days, interquartile range (IQR) 364-1,116 days], 35 (21.6%) experienced re-exploration for bleeding. The median timing of re-exploration was 6 (IQR 1-10) days. In the multivariate logistic regression analysis, postoperative platelet count was an independent predictor for re-exploration for bleeding after CF-LVAD implantation (per 10 4 /μL: odds ratio 0.83, 95% confidence interval 0.74-0.93, P=0.002). Patients who experienced re-exploration for bleeding had a significantly worse survival rate than patients who did not (at 4 years, 73.6% vs. 90.1%, P=0.039)., Conclusions: Re-exploration for bleeding is prevalent after CF-LVAD implantation, especially in patients with low postoperative platelet counts. As bleeding requiring re-exploration is associated with poor prognosis, risk stratification using the postoperative platelet count may be beneficial for these patients.

Initial screening for proteinuria by urine dipstick test (UDT) may be useful for predicting clinical outcomes. The Shinken Database includes all the new patients visiting the Cardiovascular Institute Hospital in Tokyo, Japan. Patients for whom UDT was performed at their initial visit between 2004 and 2010 (n = 7131) were divided into three groups according to the test results: negative, trace, and positive (1+ to 4+) proteinuria. During the mean follow-up period of 3.4 years, 233 (3.1%) deaths, 255 (3.6%) heart failure (HF) events, and 106 (1.5%) ischemic stroke (IS) events occurred. Prevalence of atherothrombotic risks increased with an increase in the amounts of proteinuria. The incidence of all-cause death, HF and IS events increased significantly from negative to trace to positive proteinuria groups (log rank test, P for trend < 0.001). Multivariate analysis revealed independent association between proteinuria and all-cause death [hazard ratio (HR): 1.50, 95% confidence interval (CI) 1.07-2.10], HF (HR: 1.55, 95% CI 1.14-2.12), and IS (HR: 2.08, 95% CI 1.26-3.45). Even trace proteinuria was independently associated with HF (HR: 1.64, 95% CI 1.07-2.53) and IS (HR: 2.17, 95% CI 1.14-4.11) and with all-cause death (HR: 1.56, 95% CI 0.99-2.47). In conclusions, dipstick proteinuria was independently associated with cardiovascular events and death, suggesting that the UDT is a useful tool for evaluating patients' risk for such adverse events.

Treatment and prognosis of elderly patients with atrial fibrillation (AF) may differ by the experience of fall or bone fracture. However, their current status is still unclear. From our institute database between 2010 and 2015, 674 AF patients with age ≥ 70 years were selected and were divided into those who experienced fall or fracture during the observation period (F/F group; n = 49) and those who did not (non-F/F group; n = 625). We compared the treatment and prognosis between the 2 groups. Patients in the F/F group were older (79 vs 76 years, P < 0.001) and had more comorbidities compared with those in the non-F/F group. The prescription rate of oral anticoagulant was similar between the two groups (77.6% vs 68.2%, P = 0.201), where warfarin was predominant. The F/F group was not associated with higher incidence of ischemic stroke. The F/F group was associated with a higher incidence of heart failure events (adjusted odds ratio (OR) 3.88; 95% confidence intervals (Cl) 1.70-8.85; P = 0.001), and cardiovascular events (OR 3.43; 95% Cl 1.71-6.85; P < 0.001). In elderly AF patients in a cardiovascular hospital, the experience of fall or fracture did not affect the prescription of oral anticoagulants and the incidence of ischemic stroke, but it was significantly associated with increase of heart failure.

Background: The association between cytochrome P450 (CYP) 2C19 genotypes and adverse events in patients treated with clopidogrel or prasugrel after percutaneous coronary intervention (PCI) in the Japanese population is unclear., Methods and results: This study consisted of 1,580 patients whoseCYP2C19genotypes were assessed at Shiga University of Medical Science Hospital, and 193 clopidogrel-treated and 217 prasugrel-treated patients who were followed more than 1 year after receiving PCI were analyzed. Among 1,580 patients, the prevalence of normal, intermediate, and poor metabolizers was 32%, 49%, and 17%, respectively. Overall incidence of the primary outcome, defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, ischemic stroke, or major bleeding was not significantly different between the clopidogrel and prasugrel groups (adjusted hazard ratio [HR] 1.98, 95% confidence interval [CI] 0.85-4.61, P=0.12). Among patients with theCYP2C19loss-of-function (LOF) allele, however, the incidence of the primary outcome was significantly higher in the clopidogrel group (adjusted HR 3.19, 95% CI 1.10-9.24, P=0.03), whereas no difference was observed among patients without theCYP2C19LOF allele (adjusted HR 0.67, 95% CI 0.14-3.26, P=0.62)., Conclusions: Among patients with theCYP2C19LOF allele, the use of clopidogrel was significantly associated with increased adverse events. Thus, further investigation is needed to establish the practical use ofCYP2C19genotyping.

Direct oral anticoagulants, including edoxaban, primarily do not need routine monitoring of the anticoagulant effect. However, extremely high/low plasma concentrations of edoxaban (PC-Ed) should be properly evaluated, especially when patients under anticoagulation therapy are at an emergency state. For this purpose, PC-Ed determined by an anti-Xa assay (indirect PC-Ed) is more convenient and, therefore, more useful compared with PC-Ed determined by an LC-MS/MS (direct PC-Ed) in daily clinical practice. Consecutive 97 patients with non-valvular atrial fibrillation (NVAF) under edoxaban therapy were evaluated, in whom edoxaban 60/30 mg doses were prescribed for 48/49 patients, 71 (73.2%) were men, and the average age was 69 years. CHADS 2 score 0, 1, and ≥ 2 were 26.8%, 44.3%, and 28.9%, while CHA 2 DS 2 -VASc score 0, 1, and ≥ 2 were 14.4%, 16.5%, and 69.1%, respectively. Median values of direct and indirect PC-Ed by LC-MS/MS and anti-Xa assay were 187.1 and 176.1 ng/mL at peak (2-4 h post-dose) and 14.4 and 17.5 ng/mL at trough (pre-dose), respectively. The PC-Ed at peak and trough by two methods were significantly correlated, and the correlation coefficients were r = 0.973 and 0.963 (both, p < 0.0001), respectively. By a Bland-Altman plot, mean differences between the direct and indirect PC-Ed [lower to upper percent limit of agreement] were - 4.87 [- 46.71 to 36.98] and 4.66 [- 1.37 to 10.69] ng/mL at peak and trough, respectively. Moreover, mean % error for difference between the direct and indirect PC-Ed [lower to upper percent limit of agreement] was - 1.22 [- 20.59 to 18.14] and 31.75 [- 14.03 to 77.53] % at peak and trough, respectively, where the % error extremely increased around the lower limit of detection (LLOD) in the anti-Xa assay. Strong similarity was observed between the direct and indirect PC-Ed, especially at peak. The indirect PC-Ed was higher than the direct PC-Ed, especially around the LLOD, suggesting the need for caution when we use the anti-Xa assay for measurement of trough PC-Ed (UMIN 000032492).

In Japanese surveillance in an early phase after the approval of rivaroxaban, inappropriate underdose was frequently utilized. The aim of this study was to describe the prevalence and predictors of the inappropriate usage of rivaroxaban in a single-center, cardiovascular-specialized hospital. Consecutive 661 non-valvular atrial fibrillation (NVAF) patients treated with rivaroxaban between 2012 and 2017 were recruited. After excluding 30 patients without assessment of creatinine clearance (CCr), the proportion and predictors of inappropriate underdose were analyzed. Additionally, patient outcomes, including thromboembolism (ischemic stroke or systemic embolism) and major bleeding, were determined. In patients with CCr ≥ 50 mL/min (n = 532) and < 50 mL/min (n = 98), inappropriate underdose and overdose were used in 123 (23%) and 8 (8%), respectively. The predictors of inappropriate underdose (in patients with CCr ≥ 50 mL/min) were CCr [50-63 mL/min (the lowest tertile) compared to ≥ 64 mL/min], age ( ≥ 75 years), female gender, prescription of antiplatelet, and coexistence of heart failure. Although PT under rivaroxaban was lower in patients with inappropriate underdose than in those with an appropriate dose, no significant increase in the incidence of thromboembolism or major bleeding was observed within the mean follow-up of 683 days. Inappropriate underdose of rivaroxaban was frequently observed for NVAF patents even in a cardiovascular hospital, particularly in patients with CCr adjacent to the dose reduction criteria. The responses of PT and the incidence of adverse outcomes under an inappropriate dose of rivaroxaban should be further investigated.

The aims of this study were to determine the distribution of plasma concentration of edoxaban (PC-Ed) with their 90% interval (on therapy range) and its correlation with anticoagulation markers in patients with non-valvular atrial fibrillation (NVAF). Consecutive 97 NVAF patients under edoxaban therapy were evaluated (60/30 mg dose, n = 48/49; men/women, n = 71/26; age, 69 years). CHADS 2 score 0, 1, and ≥ 2 were 27%, 44%, and 29%, respectively. The mean (90% interval) of PC-Ed by LC-MS/MS was 194.3 (49.4-345.3) and 17.0 (4.8-40.7) ng/mL at peak (2-4 h post-dose) and trough (pre-dose), respectively. Correlation of prothrombin time (PT) with PC-Ed was higher than that of activated partial thromboplastin time (aPTT). Among 6 PT reagents, Coagupia PT-N and Simplastin Excel S (both PT reagents) showed the highest predictive capability for the upper outlier of PC-Ed at peak and trough. Among 4 aPTT reagents, only Thrombocheck APTT measured at peak had a significant predictive capability. When using PT reagents, both peak and trough sampling showed a similar predictive capability for the upper outliers of PC-Ed with a high sensitivity, but a relatively low specificity. We demonstrated the distributions of plasma concentration, PT with 6 reagents, and aPTT with 4 reagents under edoxaban therapy in Japanese patients with NVAF, showing their 90% intervals. For predicting the upper outlier of PC-Ed, PT was more sensitive compared with aPTT, whereas predicting capability for the outliers of PC-Ed was mostly similar between peak and trough samplings among PT reagents (UMIN 000032492).

Objectives: Several studies have suggested a possible relationship between atrial fibrillation (AF) and falls. However, whether the relationship depends on AF types is unclear. We investigated the relationship between sustaining AF and falls., Design: Single hospital-based cohort study with a follow-up of falls within 3 years after baseline., Setting and Participants: A total of 14,056 patients from our cohort between February 2010 and March 2016., Measures: Incidence of falls within 3 years by baseline cardiac rhythm was measured, and we investigated the effects of AF types on incidence of falls., Results: The study population was divided into younger (<75 years old; n = 11,808) and older (≥75 years old; n = 2248) groups, and then divided into 3 groups according to the baseline cardiac rhythm: sinus rhythm (SR), paroxysmal AF (PAF), and persistent AF (PeAF). There were more male patients in the PeAF group; these patients had more comorbidities both in the younger and older groups. The cumulative incidence rates of falls at 1 year in patients with SR, PAF, and PeAF were similar in the younger group (0.4%, 0.4%, and 0.6%, respectively; P = .496), whereas those were significantly different in the older group (2.3%, 2.7%, and 5.0%, respectively; P = .024). In multivariate analysis, both PAF [hazard ratio (HR) 1.179; 95% confidence interval (CI) 0.553-2.511, reference SR] and PeAF (HR 1.502; 95% CI 0.635-3.556) were not associated with falls in the younger group. In the older group, PeAF was independently associated with incidence of falls (HR 2.257; 95% CI 1.262-4.037), but PAF was not (HR 1.317; 95% CI 0.673-2.574)., Conclusions/implications: PeAF, not PAF, was associated independently with falls in older patients, suggesting the possible effect of irregular beats on physical frailty in the older population., (Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Despite the increasing incidence of acute coronary syndrome (ACS) in Japan, its prognosis has improved. However, there is a paucity of longitudinal registry data providing trends of in-hospital care and prognosis of ACS in Japan. ACS patients undergoing percutaneous coronary intervention (PCI) included in the Shinken Database 2004-2014 were divided into two groups according to admission year (2004-2009, n = 390; 2010-2014, n = 328). Patient characteristics, lesion/procedure characteristics, medications at discharge, all-cause mortality, cardiovascular death, acute myocardial infarction (AMI), target lesion revascularization (TLR), re-PCI to new lesion, and coronary artery bypass graft (CABG) within 2 years after discharge were compared between the groups. Prevalence of hypertension, dyslipidemia, and dual antiplatelet/statin prescription increased significantly between periods. Usage of second-generation drug-eluting stents (DES) increased markedly between the two periods (2.6, 66.8%), while those of bare metal stents (64.4, 26.5%) and first-generation DES (25.6, 1.5%) decreased (all, p < 0.01). Two-year event-free survival rate increased for all-cause mortality (94.6-98.3%, p = 0.01), TLR (79.4-96.1%, p < 0.01), and re-PCI to new lesion (87.3-95.1%, p < 0.01). There were no significant differences in cardiovascular death, AMI, or CABG between the two periods. The event-free rates for TLR and re-PCI to new lesion in ACS patients have increased over the last decade in Japan. These observations should be confirmed in larger, longitudinal, multicenter registries.

Over the past decade, the cause of sociality has been much debated. Inclusive fitness [ br in Hamilton's rule ( br - c > 0)] has been criticized but is still useful in the organization of a framework by elucidating mechanisms through which br (benefit × relatedness) becomes larger than c (cost). The bee Lasioglossum baleicum is suitable for investigation of this issue because of the sympatric occurrence of both social and solitary nesting in its populations. We show that a large part (approximately 92%) of the inclusive fitness of a eusocial worker can be attributed to the benefits of grouping. A 1.5-fold relatedness asymmetry benefit in singly mated haplo-diploids explains a small part (approximately 8.5%) of the observed inclusive fitness. Sociality enables this species to conduct foraging and nest defense simultaneously, which is not the case in solitary nests. Our results indicate that this benefit of grouping is the main source of the increased inclusive fitness of eusocial workers.

Background: The predictive role of E/e' on ischemic stroke (IS) and atrial fibrillation (AF) in Japanese patients without AF are unclear., Methods and Results: Shinken database includes all the new patients visiting the Cardiovascular Institute Hospital in Tokyo, Japan. E/e' has been routinely measured since 2007. Patients without AF for whom E/e' was measured at the initial visit between 2007 and 2014 (n=11 477, mean age 57.2 years old, men 59.5%) were divided into E/e' tertiles (<8.04, 8.04-11.00, >11.00). During the mean follow-up period of 1.8 years, 58 IS and 140 new appearances of AF were observed. High E/e' tertile was associated with more prevalence of atherothrombotic risks. The cumulative incidence of IS events and new appearance of AF at 6 years in low, middle, and high E/e' tertiles were 0.5%, 1.4%, and 3.0%/year (log-rank test, p<0.001), and 2.5%, 2.9%, and 4.2%/year (log-rank test, p=0.007), respectively. In multivariate analysis, high E/e' tertile was independently associated with IS (HR, 2.857, 95%CI 1.257-6.495, p=0.012). Although high E/e' tertile was independently associated with new appearance of AF when adjusted for coexistence of atherothrombotic risk factors (HR, 1.694, 95%CI, 1.097-2.616, p=0.017), the association was attenuated after adjustment for left atrial dimension., Conclusions: E/e' was significantly associated with incidence of IS and new appearance of AF in non-AF patients., (Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: The relationship between mutation locations in KCNQ1 which is a major gene in long QT syndrome (LQTS) and phenotype has been analyzed and used for risk stratification. Mutations in the transmembrane region (TM) or cytoplasmic-loop (C-loop) are associated with more frequent cardiac events than those in other regions. However, accumulation of LQTS type 1 (LQT1) patients poses the question of whether the location specific risk stratification is really effective., Methods: The study cohort consisted of 67 KCNQ1 mutation carriers and 13 family members who were suspected as having LQTS due to sudden cardiac death or syncope from 36 unrelated families. The KCNQ1 mutations were L250H, V254M, H258P, and R259C located in segment 4-5 linker (C-loop), G269S, and S277L in segment 5 (TM)., Results: More than half of the patients with V254M or S277L suffered sudden cardiac death or syncope. In contrast, those with other mutations showed mild phenotype. In these two mutations related to severe phenotype, gender frequency and the age of onset were contrasting, 14 out of 23 patients with V254M were male, 19 out of 22 patients with S277L were female. In the patients we could confirm the age of onset, all of the patients with V254M showed symptoms at less than 15 years old, while 5 out of 12 patients with S277L suffered symptoms after 16 years old., Conclusion: Clinical characteristics were not specific for mutation locations but specific for respective mutations in our LQT1 patients. Patients should be evaluated by their own mutations to prevent severe cardiac events., (Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Variability in the international normalized ratio (INR) of prothrombin time has been suggested to be related to outcome in patients with atrial fibrillation (AF) under warfarin therapy, but its determinants remain unclear.Methods and Results:The study population consisted of 626 AF patients under warfarin therapy in the Shinken Database (n=22,230). INR variability was calculated by Fihn's method. Determinants of high log INR variability (defined as over mean+standard deviation) were determined by logistic regression analyses. Symptomatic heart failure (odds ratio [OR] 3.974, 95% confidence interval [CI] 2.510-6.292), older age (≥75 years old; OR 2.984, 95% CI 1.844-4.826) and severe renal dysfunction (eGFR <30 mL/min/1.73 m 2 ; OR 3.918, 95% CI 1.742-8.813) were identified as independent predictors of high INR variability on multivariate logistic regression analysis., Conclusions: The determinants of INR variability in AF patients under warfarin therapy could assist Japanese clinicians in identifying patients likely to show unstable warfarin control irrespective of the definition of the target INR range.

Background/aims: Early-stage gastric cancer (EGC) is detected even after successful Helicobacter pylori eradication. This study is aimed at clarifying the clinicopathological characteristics of EGC detected after successful H. pylori eradication., Methods: This retrospective study analyzed 57 cases of EGC detected after successful H. pylori eradication and resected endoscopically at Kyoto Prefectural University of Medicine, between January 2009 and June 2014. Clinicopathological findings of 57 cases (H. pylori-eradicated group) were investigated, and compared with those in active H. pylori infection resected in the same period (H. pylori-positive group)., Results: Most EGCs were detected in patients with severe atrophic mucosa, both in H. pylori-eradicated and H. pylori-positive groups, while the percentage of EGC detected in patients with mild atrophic mucosa gradually increased over time from successful eradication (H. pylori-positive: 7%, up to the fourth year since eradication: 11%, after the fifth year since eradication: 32%). The percentage of EGC detected in patients with mild atrophic mucosa after the fifth year since eradication was significantly higher than that in patients with active H. pylori infection (p = 0.004)., Conclusion: After the fifth year following eradication, we should be alert to the incidence of EGC, irrespective of the severity of mucosal atrophic change., (© 2017 S. Karger AG, Basel.)

Background and Aim: Generally, colorectal endoscopic submucosal dissection (ESD) cannot be carried out with severe lens cloudiness. We examined the occurrence of lens cloudiness during ESD as well as the efficacy of a novel cleaner for it., Methods: This study was a prospective study compared to historical control. First, we analyzed 103 ESD cases using standard cleaner at the Kyoto Prefectural University of Medicine in 2012. Relationship between lens cloudiness and clinical characteristics of lesions was analyzed. Lens cloudiness was recorded as grade 0 (clear) to grade 2 (very unclear). Then, we recruited 92 consecutive patients who underwent colorectal ESD using the novel cleaner from August 2013 to July 2014. The cleaner was applied on top of the lens before procedure and ability to prevent lens cloudiness was tested. Additionally, the novel cleaner was injected from endoscopic channel into a space created by endoscopic hood and colonic wall in seven cases with grade 1 or 2 of lens cloudiness and the ability to clean lens cloudiness inside the colon was tested., Results: Rate of severe lens cloudiness was 8.7%. Multivariate analysis showed that severe lens cloudiness was related with severe submucosal fatty tissue (P < 0.001). The novel cleaner had significantly less cloudiness cases compared to the standard cleaner (14.1% vs 33.0%, P = 0.002). Additionally, the novel cleaner enabled us to clean lens cloudiness in all seven cases., Conclusion: Lens cloudiness during ESD was associated with submucosal fatty tissue. Effective lens cleaner should be used to prevent and clean lens cloudiness., (© 2015 The Authors. Digestive Endoscopy © 2015 Japan Gastroenterological Endoscopy Society.)

Repeated hospitalization due to acute decompensated heart failure (HF) is a pandemic health problem in Japan. However, it is difficult to predict rehospitalization after discharge for acute decompensated HF. We used a single hospital-based cohort from the Shinken Database 2004-2012, comprising all new patients (n = 19,994) who visited the Cardiovascular Institute Hospital. A total of 282 patients discharged after their first acute HF admission were included in the analysis. The median follow-up period was 908 ± 865 days. Of these patients, rehospitalization due to worsening HF occurred in 55 patients. The cumulative rate of rehospitalization was 17.5% at 1 year, 21.4% at 2 years, and 25.5% at 3 years. Patients with rehospitalization were older than those without rehospitalization. Prevalence of diabetes mellitus (DM) was more common in patients with rehospitalization. Average heart rate (HR) tended to be higher in patients with rehospitalization. Loop diuretics were more commonly used at hospital discharge in patients with rehospitalization. Multivariate Cox regression analysis revealed that age ≥ 75 years, DM, HR ≥ 75 bpm at discharge, and use of loop diuretics at discharge were independent predictors for rehospitalization. The number of these independent risk factors could be used to clearly discriminate between the HF rehospitalization low-, middle- and high-risk patients. HF rehospitalization commonly occurred in patients who were discharged after their first acute HF admission. Older age, DM, increased HR, and loop diuretics use at discharge were independently associated with HF rehospitalization. By simply counting these risk factors, we might be able to predict the risk of HF rehospitalization after discharge.

Background: Transnasal esophagogastroduodenoscopy (EGD) without sedation has been reported to be safe and tolerable. It has recently been used widely in Japan for the detection of upper gastrointestinal disease. Alternatively, transoral examination using a thin endoscope has also been reported to be highly tolerable., Objective: To examine the cardiocirculatory effects of transoral versus transnasal EGD in an attempt to determine the most suitable endoscopic methods for patients ≥75 years of age., Methods: Subjects who underwent monitoring of respiratory and circulatory dynamics without sedation during endoscopic screening examinations were enrolled at the New Ooe Hospital (Kyoto, Japan) between April 2008 and March 2009. A total of 165 patients (age ≥75 years) provided written informed consent and were investigated in the present study. Patients were randomly divided into three subgroups: UO group--thin endoscope; SO group--standard endoscope; and UT group--transnasal EGD. Percutaneous arterial blood oxygen saturation, heart rate and blood pressure were evaluated just before EGD and at five time points during EGD. After transnasal EGD, patients who had previously been examined using transoral EGD with a standard endoscope were asked about preferences for their next examination., Results: There were no statistical differences in the characteristics among the groups. Percutaneous oxygen saturation in the UT group showed a transient drop compared with the SO and UO groups at the beginning of the endoscopic procedure. Heart rate showed no significant differences among the SO, UO and UT groups; Systolic blood pressure in the UO group was lower immediately after insertion compared with the SO and UT groups. The rate pressure product in the UO group was comparable with that in the UT group during endoscopy, and the SO group showed a continuously higher level than the UO and UT groups. More than one-half (54.4%) of patients were 'willing to choose transnasal EGD for next examination'., Conclusions: For elderly patients, unsedated transnasal EGD failed to show an advantage over unsedated standard endoscopy. Transoral thin EGD was estimated to be safe and tolerable.

Background: An electronic system for salt intake assessment using a 24-h dietary recall method has been developed in Japan. We evaluated the validity of this salt intake system for assessing salt intake., Methods: We prospectively obtained data on estimated salt intake using 24-hour urinary sodium excretion (24-hUNaCl) and salt intake by the salt intake assessment system from 203 consecutive outpatients with essential hypertension (age: 67.8 ± 10.7 years; 53.7% men)., Results: Mean values were 9.7 ± 2.9 g/day for 24-hUNaCl and 9.1 ± 2.9 g/day for the salt intake assessment system before corrections. The salt intake estimated by the present system was significantly correlated with 24-hUNaCl (r = 0.66, p < 0.0001). After corrections for habitual use of discretionary seasonings, habitual intake of salty foods, and physical activity, correlation coefficients between salt intake and 24-hUNaCl increased from 0.60 to 0.66 in men <65 years, from 0.80 to 0.81 in men ≥ 65 years, from 0.64 to 0.75 in women <65 years, and from 0.52 to 0.59 in women ≥ 65 years. After further correction for regional differences in average salt intake, the correlation coefficient reached 0.72 in all patients., Conclusion: After correction for dietary habits, lifestyle factors, and differences in average salt intake by region, this system may be a useful tool in Japan to encourage salt restriction in the clinical treatment of hypertension and improve public health in terms of salt restriction overall.

We examined whether the rate of eating was associated with the body mass index and glycemic control status in Japanese patients with type 2 diabetes (50% women, mean±SD age 59.4±7.5 years). Rapid eating was significantly associated with body mass index (p=0.047). The body mass index of those who reported eating quickly was 0.8 kg/m² higher than in individuals who reported eating at medium speed even after adjustment for known confounders. No significant association was observed between the rate of eating and HbA(1c). Our findings suggest an association between self-reported rapid eating and an elevated body mass index in patients with type 2 diabetes., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background and Aim: Adequate mucosal elevation by submucosal injection is important for definitive en bloc resection and prevention of perforation during endoscopic mucosal resection (EMR). The objective of this study is to determine the efficacy of 0.13% hyaluronic acid (HA) solution for high and sustained mucosal elevation during colorectal EMR., Methods: The study was a prospective randomized controlled trial; a total of 196 patients with colon polyps of < 20 mm diameter were enrolled and randomized in a 1:1 ratio to undergo EMR using either 0.13% HA or normal saline (NS). The primary outcome of the study was histopathologically confirmed complete resection. The secondary outcomes such as maintenance of high mucosal elevation and development of complications were also evaluated. Moreover, the relationship between complete resection and the experience of the endoscopist (veteran vs less experienced) was analyzed., Results: Compete resection was achieved in 74 of 93 polyps (79.5%) in the 0.13% HA group and 63 of 96 polyps (65.6%) in the NS group (P < 0.05). High mucosal elevation was maintained in 83.9% of procedures in the 0.13% HA group and 54.1% in the NS group (P < 0.01). The frequency of complete resection achieved by less-experienced endoscopists was higher in the 0.13% HA group (79.3%) than in the NS group (62.1%; P < 0.05)., Conclusions: Endoscopic mucosal resection using 0.13% HA to colon polyps of less than 20 mm diameter is more effective than NS for complete resection and maintenance of mucosal elevation., (© 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Introduction: This study examined the clinical profile of cluster headaches in Japan and the potential presence of features peculiar to Japan. Most previous studies of cluster headaches have focused on Caucasian populations., Methods: Subjects comprised 86 consecutive new cluster headache patients (68 males, 18 females; mean age, 38.4 ± 12.2 years; range, 17-73 years). Mean age at onset was 31.0 years and the ratio of males to females was 3.8:1., Results: Chronic cluster headache was observed in 3.5% of patients. More than half of patients (68.9%) reported feelings of restlessness during headache episodes and 42.9% reported restless behaviour. Patients with uncoupling of feelings of restlessness and restless behaviour forced themselves to keep still. Similar findings were reported in a Taiwanese study., Conclusion: Japanese patients in this study showed a relatively low prevalence of chronic cluster headaches, and uncoupling of a sense of restlessness and restless behaviour. These features of cluster headache may be more common in Japanese and Taiwanese patients than in Caucasian patients.

We present the case of a patient who was referred to our hospital after she reported having passed a long, whitish object per rectum. Accordingly, capsule endoscopy was performed using the PillCam(®) SB video capsule. A tapeworm of the species Diphyllobothrium nihonkaiense was detected; it appeared to be freely floating and unfolded in the jejunum and sometimes tangled or irregularly folded in the ileum. The stretching of the strobila by strong peristalsis in the ileum may have resulted in the separation of the caudal portion of the strobila, which descended into the colon and was eventually passed per rectum., (© 2011 The Japanese Society of Internal Medicine)

Aim: To evaluate a new hemostatic method using hemostatic forceps to prevent perforation and perioperative hemorrhage during colonic endoscopic submucosal dissection (ESD)., Methods: We studied 250 cases, in which ESD for colorectal tumors was performed at the Kyoto Prefectural University of Medicine or Nara City Hospital between 2005 and 2010. We developed a new hemostatic method using hemostatic forceps in December 2008 for the efficient treatment of submucosal thick vessels. ESD was performed on 126 cases after adoption of the new method (the adopted group) and the new method was performed on 102 of these cases. ESD was performed on 124 cases before the adoption of the new method (the unadopted group). The details of the new method are as follows: firstly, a vessel was coagulated using the hemostatic forceps in the soft coagulation mode according to the standard procedure, and the coagulated vessel was removed using the forceps in the "endocut" mode without perioperative hemorrhage. Secondly, the partial surrounding submucosa was dissected using the forceps in the endocut mode. In the current study, we evaluated the efficacy of this method., Results: Coagulated vessels were successfully removed using the hemostatic forceps in all 102 cases without severe perioperative hemorrhage. Moderate perioperative hemorrhage occurred in five cases (4.9%); however, it was stopped by immediately reuse of the hemostatic forceps. The partial surrounding submucosa was dissected using the forceps in all 102 cases. In the adopted group, the median operation time was 105 min. The proportion of endoscopic en bloc resection was 92.8% (P < 0.01) compared to 80.6% in the unadopted group. The postoperative hemorrhage and perforation rates were 2.3% and 2.3%. The rate of perforation was significantly lower than that in the unadopted group (9.6%, P < 0.01). We evaluated the ease of use of this method by allowing our three trainees to performed ESD on 46 cases, which were accomplished without any severe hemorrhage., Conclusion: The new method effectively treated submucosal thick vessels and shows promise for the prevention of perforation and perioperative hemorrhage in colonic ESD.

Background: Optimal treatment strategies for restenosis of sirolimus-eluting stents (SES) have not been adequately addressed yet., Methods and Results: During the 3-year follow-up of 12 824 patients enrolled in the j-Cypher registry, 1456 lesions in 1298 patients underwent target-lesion revascularization (TLR). Excluding 362 lesions undergoing TLR for stent thrombosis or TLR using treatment modalities other than SES or balloon angioplasty (BA), 1094 lesions with SES-associated restenosis in 990 patients treated with either SES (537 lesions) or BA (557 lesions) constituted the study population for the analysis of recurrent TLR and stent thrombosis after the first TLR. Excluding 24 patients with both SES- and BA-treated lesions, 966 patients constituted the analysis set for the mortality outcome. Cumulative incidence of recurrent TLR in the SES-treated restenosis lesions was significantly lower than that in the BA-treated restenosis lesions (23.8% versus 37.7% at 2 years after the first TLR; P<0.0001). Among 33 baseline variables evaluated, only hemodialysis was identified to be the independent risk factor for recurrent TLR by a multivariable logistic regression analysis. After adjusting for confounders, repeated SES implantation was associated with a strong treatment effect in preventing recurrent TLR over BA (odds ratio, 0.44; 95% confidence interval, 0.32 to 0.61; P<0.0001). The 2-year mortality and stent thrombosis rates between the SES- and the BA-treated groups were 10.4% versus 10.8% (P=0.4) and 0.6% versus 0.6%, respectively., Conclusions: Repeated implantation of SES for SES-associated restenosis is more effective in preventing recurrent TLR than treatment with BA, without evidence of safety concerns.

Patients with severe primary headache may benefit from consultation with headache specialists, but doctor attendance rates in Japan are very low. More headache patients might consult headache specialists if these specialists were more widely recognized by the public. To determine what information prompted patients to seek consultation with a headache specialist, we questioned 256 primary headache patients about the source of the helpful information concerning consultation with headache specialists. From 191 patients, a total of 235 responses to the questionnaire were obtained. The most common response was 'websites' (33.2%), followed by 'professionals' (23.8%), 'acquaintances' (20.9%), 'print media' (6.8%) and 'TV/radio' (3.4%). Patients who indicated websites showed the most severe pain and highest impact of headache, and accounted for 52.4% of those with cluster headaches. Development of websites concerning headache specialists would seem likely to increase doctor attendance rates for patients with primary headache.

Marked differences have been reported in the prevalence of glutamic acid decarboxylase (GAD) antibodies between Caucasian (63-84%) and Japanese (30-50%) or Asian (5-50%) IDDM patients. Using a new immunoprecipitation assay based on 125I-labelled recombinant human GAD65 we have reassessed prevalence of GAD65 antibodies in Japanese patients. We also assessed prevalence of IA-2 antibodies. GAD65 antibodies were detected in 83.3% of sera taken within 1 year of onset, comparable to the prevalence reported in Caucasian patients. Positivity decreased to 66.7% after 2 to 3 years and to 54.3% after 3 years from onset, still higher than previously reported Asian prevalence. Except in one patient, high antibody levels persisted chronically, up to 12 years. There was no difference in the prevalence of GAD65 antibodies between Japanese IDDM patients with and without autoimmune thyroid disease (AITD). IA-2 antibodies were detected in 64.7% of sera taken within 1 year of onset. Prevalence of IA-2 antibodies was lower than that of GAD65 antibodies. The difference in positivity in Asian IDDM patients between present and previous reports arose from the sensitivity of our assay for GAD65 antibodies. Additionally, the patients we studied had classic IDDM with a well-defined onset. We conclude that prevalence of GAD65 antibodies in Japanese IDDM patients is comparable to that in Western studies. There was no relationship of GAD65 antibody positivity to coexistence of AITD. Our results suggest that autoimmunity is the most significant cause of Japanese IDDM.