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Background: This study aimed to quantify the readability and quality of online patient resources on knee osteoarthritis and lumbar spinal stenosis in Japan., Methods: Three search engines (Google, Yahoo, and Bing) were searched for the terms knee osteoarthritis and lumbar spinal stenosis. The first 30 websites of each search were screened. Duplicate websites and those unrelated to the searched diseases were excluded. The remaining 125 websites (62 on knee osteoarthritis, 63 on lumbar spinal stenosis) were analyzed. The text readability was assessed using two web-based programs (Obi-3 and Readability Research Lab) and lexical density. Website quality was evaluated using the DISCERN score, Clear Communication Index, and Journal of American Medical Association benchmark criteria., Results: Readability scores were high, indicating that the texts were difficult to understand. Only 24 (19%) and six (5%) websites were classified as average difficulty readability according to Obi-3 and Readability Research Lab, respectively. The overall quality of information was low, with only four (3%) being rated as having sufficient quality based on the Clear Communication Index and Journal of American Medical Association benchmark criteria. None of the websites satisfied the DISCERN quality criteria., Conclusions: Patient information on Japanese websites regarding knee osteoarthritis and lumbar spinal stenosis were difficult to understand. Moreover, the quality of the websites was insufficient. Orthopaedic surgeons should contribute to the creation of high-quality easy-to-read websites to facilitate patient-physician communication., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Real-world data assessing characteristics of patients with asthma initiating inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β 2 -agonist (ICS/LAMA/LABA) triple therapy in Japan are limited., Methods: Descriptive, observational study of patients with asthma aged ≥15 years newly initiating single- or multiple-inhaler triple therapy (SITT: fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI], SITT: indacaterol/glycopyrronium bromide/mometasone furoate [IND/GLY/MF] or MITT) or ICS/LABA using JMDC/Medical Data Vision (MDV) health insurance databases from February 2021-February 2022 (first prescription date: index date). Patients were assigned to three non-mutually exclusive cohorts: A) new FF/UMEC/VI initiators; B) new FF/UMEC/VI, IND/GLY/MF, or MITT initiators; C) new FF/UMEC/VI, IND/GLY/MF, MITT or ICS/LABA initiators as initial maintenance therapy (IMT). Patient characteristics were assessed descriptively for 12-months pre-treatment initiation (baseline period)., Results: Cohort A: among new FF/UMEC/VI initiators, 12.8% and 0.1% (JMDC) and 21.7% and 0.9% (MDV) of patients had ≥1 moderate and severe exacerbation; 52.0% (JMDC) and 79.2% (MDV) had ICS/LABA use. Cohort B: most patients initiated FF/UMEC/VI and IND/GLY/MF over MITT (JMDC: 91.3% vs 8.7%; MDV: 67.8% vs 32.2%), with fewer exacerbations and lower rescue medication use. Cohort C: a greater proportion of FF/UMEC/VI initiators as IMT experienced a moderate exacerbation at index versus ICS/LABA initiators as IMT (JMDC: 17.8% vs 10.7%; MDV: 8.0% vs 5.1%)., Conclusions: Patient characteristics were generally similar between treatment groups; SITT initiators had fewer exacerbations and lower rescue medication use than MITT initiators, represented by the greater proportion of IMT among SITT versus MITT initiators. Physicians may have prescribed triple over dual therapy as IMT in response to an exacerbation., Competing Interests: Declaration of competing interest TO has received lecture fees from GSK K.K., Nippon Boehringer Ingelheim Co. Ltd, AstraZeneca K.K., Novartis Pharma K.K., and Teijin Healthcare Ltd. CM, RI, GR, KJR, SGN, LY, and MY are employees of GSK and may hold stocks/shares in GSK, or were at the time of the study. SGN is a PhD candidate at McMaster University, Hamilton, Ontario, Canada., (Copyright © 2024. Published by Elsevier B.V.)

Background: We analyzed the influence of the QRS duration (QRSd) to LV end-diastolic volume (LVEDV) ratio on cardiac resynchronization therapy (CRT) outcomes in heart failure patients classified as III/IV per the New York Heart Association (NYHA) and with small body size., Hypothesis: We proposed the hypothesis that the QRSd/LV size ratio is a better index of the CRT substrate., Methods: We enrolled 114 patients with advanced heart failure (NYHA class III/IV, and LV ejection fraction >35%) who received a CRT device, including those with left bundle branch block (LBBB) and QRSd ≥120 milliseconds (n = 60), non-LBBB and QRSd ≥150 milliseconds (n = 30) and non-LBBB and QRSd of 120-149 milliseconds (n = 24)., Results: Over a mean follow-up period of 65 ± 58 months, the incidence of the primary endpoint, a composite of all-cause death and hospitalization for heart failure, showed no significant intergroup difference (43.3% vs. 50.0% vs. 37.5%, respectively, p = .72). Similarly, among 104 patients with QRSd/LVEDV ≥ 0.67 (n = 54) and QRSd/LVEDV < 0.67 (n = 52), no significant differences were observed in the incidence of the primary endpoint (35.1% vs. 51.9%, p = .49). Nevertheless, patients with QRSd/LVEDV ≥ 0.67 showed better survival than those with QRSd/LVEDV < 0.67 (14.8% vs. 34.6%, p = .0024)., Conclusion: Advanced HF patients with a higher QRSd/LVEDV ratio showed better survival in this small-body-size population. Thus, the risk is concentrated among those with a larger QRSd, and patients with a relatively smaller left ventricular size appeared to benefit from CRT., (© 2024 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background: Since the Fukushima Daiichi nuclear power plant (FDNPP) accident in 2011, measures have been taken to address occupational health risks, such as heat illness and infectious diseases, and ensure fitness for duty with the Tokyo Electric Power Company and its contractors. However, with the decommissioning operations set to span several decades and an aging workforce, there arose a need for proactive occupational health strategies that not only addressed these risks but also promoted employee health and created a comfortable work environment. With the Japanese government's promotion of health and productivity management (HPM) for corporations, an HPM-based initiative was launched at the FDNPP in 2019., Case: We designed an HPM questionnaire tailored to the unique conditions at the FDNPP for contractors in 2019. Subsequently, we adjusted the questionnaire annually in light of evolving societal contexts and insights derived from contractors' feedback. This initiative also involved the annual recognition of outstanding contractors. These efforts have led to a steady increase in the number of contractors participating in the HPM survey, with respondents' scores continually improving. We also emphasized dissemination of HPM practices from contractors to their subcontractors due to the complex subcontracting structure at FDNPP, and our results showed that more contractors have been extending these efforts to their subcontractors., Conclusions: Our findings suggest that individual contractors are steadily enhancing their HPM efforts. We are committed to continually offering support to advance HPM throughout the FDNPP., (© The Author(s) [2024]. Published by Oxford University Press on behalf of Journal of Occupational Health.)

In 2020, the Japan Community Healthcare Organization (JCHO) Hoshigaoka Medical Center started providing information to community pharmacies about patients admitted to the acute care ward using discharge medication summaries (the summaries). We conducted an online self-recording survey of 149 pharmacies belonging to the Hirakata City Pharmacists Association to clarify the usability of the summaries, any related issues, and to further discuss future collaboration between hospitals and pharmacies. 46 pharmacies have received the summaries in the past, of which 44 pharmacies answered that they have utilized the summaries with patient instruction and prescription queries of doctors. However, two pharmacies responded they did not utilize the summaries, and the reasons were (a) the information was not timely and (b) patients whom the discharge medical summary was sent for did not come to the pharmacy. There were some requests regarding the summaries such as, "I would like to know what kind of information hospital pharmacists want from community pharmacists." Preference for sharing information other than the summaries (e.g., online tools) with hospital pharmacists was related to whether the pharmacy was providing home pharmaceutical visit services. The survey revealed that, in addition to the usability of the summaries, there are also events that prevent them from being utilized. Some of the challenges include the timing of sending the summaries, the accurate identification of the family pharmacy and the communication of follow-up after discharge from hospital. Collaborating with pharmacies providing home pharmaceutical visit services would be beneficial in creating new system of bidirectional information sharing.

Introduction: There is limited information regarding multidimensional relationships between asthma control and health-related quality of life (HRQoL), work productivity, and asthma symptom burden in Japan. Furthermore, systematic qualitative investigations about asthma burden have not been performed., Methods: This cross-sectional, mixed-methods study included Japanese patients (≥ 20 years) with asthma adherent to inhaled corticosteroids/long-acting β 2 -agonists (ICS/LABA). The primary endpoint was impact of asthma on HRQoL, measured using the Asthma Health Questionnaire-33 (AHQ-33). Secondary endpoints were cough burden (Japanese-adapted Leicester Cough Questionnaire [J-LCQ]) and impact of asthma on work/activities (asthma-specific Work Productivity and Activity Impairment Questionnaire [WPAI:Asthma]). Quantitative data were assessed for the overall population and for well-controlled (WC) and not well-controlled (NWC) asthma subgroups. Qualitative verbal interviews further assessed the impact of NWC asthma on patients' HRQoL; emergent themes were extracted using thematic analyses., Results: Of 454 patients, 45.2% (n = 205) had NWC asthma. Patients with NWC asthma had significantly worse asthma- and cough-related HRQoL across all AHQ-33 and J-LCQ domains and significantly greater work and activity impairment versus patients with WC asthma, across all assessed WPAI:Asthma domains. AHQ-33 total score was highly correlated with J-LCQ total and domain scores (r = - 0.8132 to r = - 0.7407). Nine themes emerged from qualitative interviews and confirmed that patients with NWC asthma had considerable HRQoL impairment due to asthma symptoms., Conclusions: Patients with NWC asthma had higher symptom burden and worse HRQoL than patients with WC asthma, despite ICS/LABA adherence. Cough burden correlated with HRQoL, suggesting cough may be one of the key markers to inform treatment strategy for patients with asthma., (© 2023. The Author(s).)

The proportion of pediatric cases with severe acute hepatitis of unknown etiology in the coronavirus disease 2019 era was higher than that in the pre-coronavirus disease 2019 era in Japan's largest pediatric transplant center. Further research and monitoring are essential., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: The COVID-19 pandemic has drastically changed global lifestyles. Some reports about lifestyle changes during this pandemic have been published. However, these studies have not assessed gender differences. Thus, we analyzed three lifestyle changes to determine gender differences., Methods: We analyzed physical activity, snacking habits, and drinking habits in 323 patients with diabetes. Gender differences in lifestyle habits were analyzed using the ꭓ 2 test, and comparisons of HbA1c between 2019 and 2020 were analyzed using the paired t-test. The factors that influenced the deterioration of HbA1c were determined using multivariate logistic regression analyses., Results: Of the 323 patients, 212 were male and 111 were female. When examined by quarter, the HbA1c values increased significantly in 2020 compared with that in 2019 in the July-September period. In terms of gender differences in the changes of lifestyle habits, decreased physical activity was higher in women. The factors that affected deterioration in HbA1c were snacking habits for the overall and the male populations., Conclusions: The lifestyle changes differed between the genders during the pandemic. A balanced diet is important for all patients with diabetes. Additionally, more attention should be paid to physical inactivity in women., (Copyright © 2022 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Objective In this study, we investigated whether and how the COVID-19 pandemic affected glycemic control and blood pressure (BP) control in patients with diabetes mellitus (DM). Methods DM patients whose HbA1c level was measured regularly before and after the declaration of a state of emergency were included in this study. Some patients were given questionnaires about changes in their lifestyle to determine the factors affecting glycemic control and BP control. Results The median HbA1c level of the 804 patients increased significantly from 6.8% before the state of emergency to 7.1% and 7.0% during and after the state of emergency, respectively. This was in contrast to the decrease one year earlier due to seasonal variations. In the 176 patients who responded to the questionnaire, the HbA1c level also increased significantly during and after the state of emergency. The worsening of glycemic control was more pronounced in the group that had achieved HbA1c of <7% before the state of emergency than in those with higher values. Unlike the rise in HbA1c, the BP did not rise during the state of emergency but did rise significantly afterwards. There was no marked decrease in HbA1c or BP after the state of emergency, even in patients who responded that they were much more careful with their diet, ate less, or exercised more. Conclusions The COVID-19 pandemic worsened glycemic control and BP control, even in patients who perceived no marked change in their diet or exercise, suggesting that more active lifestyle guidance is necessary for good treatment of DM patients.

Objectives: This study sought to examine differences in the economic losses due to presenteeism and costs of medical and dental treatment between high-stress workers and non-high-stress workers using the stress check survey., Methods: We conducted a cross-sectional study from April 1, 2018 to March 31, 2019 in a pharmaceutical company. High-stress workers were classified with the Brief Job Stress Questionnaire using two methods: the sum method and the score converted method. The incidence of presenteeism and its costs were determined using a questionnaire. The costs of medical and dental treatment were calculated according to claims. We compared the costs between high-stress and non-high-stress workers using Wilcoxon's rank-sum test., Results: Of 3910 workers, 6.3% were classified as high-stress using the sum method and 6.6% were classified as high-stress using the score converted method. The costs associated with presenteeism and medical treatment among high-stress workers were higher than the costs among non-high-stress workers, whereas the costs associated with dental treatment were not., Conclusions: To motivate employers to improve stressful work environments, it is recommended that presenteeism measurement items be added to the stress check survey, and that the methods used in this study be used to calculate the loss associated with high-stress workers in Japanese companies. However, we must be careful in interpreting absolute presenteeism loss amounts because they are poorly reliable and valid., (© 2022 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.)

We conducted a risk-adapted upfront docetaxel (DOC) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Here, we reported an interim analysis of the study. The study enrolled 68 patients with newly diagnosed mHSPC between 2016 and 2018. According to the presence of visceral metastasis, an EOD score ≥ 3, or prostate-specific antigen (PSA) level at 3 months of ≥ 1 ng/mL, patients were divided into low- and high-risk groups. Patients were treated with androgen deprivation therapy (ADT) with or without bicalutamide; those in the high-risk group received upfront treatment involving six cycles of DOC (70 mg/m 2 ). Short-term treatment effect, adverse events, and quality of life (QOL) were evaluated. Fifty (73.5%) were classified in the high-risk group, and 46 (67%) received upfront ADT + DOC. In the ADT + DOC group, 43.5% (20/46) patients achieved a PSA level ≤ 0.2 ng/mL. PSA nadir and time to PSA nadir were 0.291 ng/mL and 288 days, respectively. In the ADT + DOC group, 76.1% (35/42) patients had adverse events (AEs) of grade ≥ 3. During a median follow-up of 18.5 months, 36.4% (8/22) patients in the ADT group and 43.5% (20/46) in the ADT + DOC group had CRPC. Two QOL scores including the physical status and appetite loss at 6 months significantly worsened in the ADT + DOC group but was resolved by 12 months. Upfront DOC achieved high PSA responses without long-term QOL deterioration. However, the short-term outcomes were limited. Longer follow-up is needed to determine the survival advantage.

A patient in Japan with coronavirus disease and hypervirulent Klebsiella pneumoniae K2 sequence type 86 infection died of respiratory failure. Bacterial and fungal co-infections caused by region-endemic pathogens, including hypervirulent K. pneumoniae in eastern Asia, should be included in the differential diagnosis of coronavirus disease patients with acutely deteriorating condition.

Objectives: The health effects of telework, which was introduced extensively in the immediate context of the COVID-19 pandemic crisis in Japan, on teleworkers, their families, and non-teleworkers, are unknown. Accordingly, we developed a rapid health impact assessment (HIA) to evaluate positive and negative health effects of telework on these groups and recommended easily implementable countermeasures., Methods: Immediately after an emergency was declared in Japan, we implemented a rapid, five-step HIA. We screened and categorized health effects of telework for the three above-mentioned groups, extracting their content, directionality, and likelihood. Following a scoping exercise to determine the HIA's overall implementation, five experienced occupational health physicians appraised and prioritized the screened items and added new items. We outlined specific countermeasures and disseminated the results on our website. A short-term evaluation was conducted by three external occupational health physicians and three nurses., Results: Following screening and appraisal, 59, 29, and 27 items were listed for teleworkers, non-teleworkers, and family members of teleworkers, respectively, covering work, lifestyle, disease and medical care, and home and community. Targeted countermeasures focused on the work environment, business management, communications, and lifestyles for teleworkers; safety and medical guidelines, work prioritization, and regular communication for non-teleworkers; and shared responsibilities within families and communication outside families for family members of teleworkers., Conclusion: The HIA's validity and the countermeasures' practical applicability were confirmed by the external evaluators. They can be easily applied and adapted across diverse industries to mitigate the wider negative effects of telework and enhance its positive effects., (© 2021 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.)

Previous studies have shown that the sudden cardiac death (SCD) prediction model proposed by the 2014 European Society of Cardiology (ESC) guideline (5-Year Risk-SCD) was validated in European patients with hypertrophic cardiomyopathy (HCM). However, there are limited data on Asian patients with HCM. We assessed the validity of the estimated 5-Year Risk-SCD in Japanese HCM patients with an implantable cardioverter-defibrillator (ICD) using the2014 ESC guidelines. We retrospectively examined data of 492 consecutive Japanese patients with an ICD. Sixty-two Japanese HCM patients with an ICD were enrolled in this study, and 50 patients (81%) were followed up for ≥ 5 years. We analyzed the characteristics and outcomes of these 50 patients. We investigated the incidence of appropriate ICD therapy as categorized by the ESC guideline and compared the 5-Year Risk-SCD with the 5-year rate of appropriate shock therapies. Based on the 2012 Japanese Circulation Society guideline and the 2011guidelines of the American Heart Association and American College of Cardiology Foundation, 10 and 40 patients met classes I and IIa of the ICD recommendation, respectively. However, only 18 (36%) patients were classified into class I or IIa of the ESC guideline. Among 50 patients followed up for ≥ 5 years after ICD implantation, the incidences of appropriate ICD therapies for classes I, IIa, IIb, and III indications based on the 2014 ESC guideline were 50%, 38%, 17%, and 0%, respectively. Risk stratification for SCD using 5-Year Risk-SCD is valid in Japanese HCM patients with an ICD, and the 2014 ESC guideline might be useful for the indication of ICD implantation in Japan.

Objectives: To follow up arising occupational health (OH) issues, measures taken, and their performances in the Fukushima Daiichi Nuclear Power Plant since 2014, and thus share experiences and extend the contribution of OH to long-term decommissioning work and preparation for future disasters., Methods: Necessary information from official reports and through the OH-related activities involved was collected and analyzed., Results: The issues were categorized into establishment of the OH management system, three individual issues, and others. During the 6 years until end 2019, the OH management system has been strengthened and OH measures have been enriched gradually by visualizing the broader picture, even though some resistance and problems have been encountered., Conclusions: Improvement in the autonomy of contractors and their ability to respond to environmental changes is necessary.

Background: Leads are often considered the weakest link in implantable cardioverter-defibrillator (ICD) systems, and lead dysfunction is a major concern for ICD recipients. The aim of this study was to compare the lead performance from three different manufacturers., Methods: We retrospectively reviewed consecutive patients who underwent ICD system implantation at Chiba University Hospital, Japan, between March 2008 and September 2017. The following leads were implanted in our center: Durata (St. Jude Medical, St. Paul, MN, USA, now Abbott) (n = 105), Linox and Linox Smart (Biotronik, Berlin, Germany) (n = 66), and Sprint Quattro (Medtronic, Minneapolis, MN, USA) (n = 126)., Results: A total of 297 ICD leads were analyzed. Failure rates for Durata, Linox/Linox Smart , and Sprint Quattro were 0.20%/patient year, 0.95%/patient year, and 1.84%/patient year, respectively, during a mean follow-up of 4.8, 6.4, and 3.0 years, respectively. The cumulative ICD lead survival probability was 98.9%, 100%, and 87.5%, after 5 years, respectively. The survival probability over the entire follow-up time as measured by the log-rank test was lower for Sprint Quattro leads than for either Durata (p = 0.011) or Linox/Linox Smart (p = 0.028). The difference between Durata and Linox/Linox Smart was not significant (p = 0.393)., Conclusions: In this single-center retrospective study, the performance of Sprint Quattro was lower than the performance of Linox/Linox Smart and Durata leads. Large-scale, multi-center studies or manufacturer-independent registries may be necessary to confirm or reject self-reported survival probabilities from manufacturers' product performance reports.

Objectives: This study aimed to consider the appropriate occupational health system for Japanese enterprises in the Philippines based on information on the regulations and development of specialists., Methods: We collected information using an information-gathering checklist. Along with literature and internet surveys, we conducted interviews by visiting local business sites, central government agencies in charge of medical and health issues, and educational institutions with specialized occupational physician training curricula., Results: Occupational health administration in the Philippines is managed by the Department of Labor and Employment, which issues the Occupational Safety and Health Standards that specify the legal requirements for occupational health. A new law(Republic Act 11058),enacted in 2018 to strengthen the Occupational Safety and Health Standards, has newly established a penalty provision in case of violations. Professional personnel responsible for occupational health are grouped as safety officers and occupational health personnel, including occupational physicians and occupational nurses; training is conducted at the Occupational Safety and Health Center of the Department of Labor and Employment and educational institutions. The basic medical insurance system and the workers' compensation system are operated by the Philippine Health Insurance Corporation and Social Security Committee, respectively, both of which are government agencies., Conclusions: We confirmed that occupational health activities in the Philippines are based on government regulations, namely, the Occupational Safety and Health Standards. In addition, the enactment of a new law calls for strict compliance with corporate occupational health activities. To manage proper occupational health activities at overseas workplaces, Japanese corporations should clarify corporate-wide policies and support local employers in complying with regulations and utilizing highly specialized personnel.

Background: Hepatocerebral mitochondrial DNA depletion syndrome (MTDPS) is a disease caused by defects in mitochondrial DNA maintenance and leads to liver failure and neurological complications during infancy. Liver transplantation (LT) remains controversial due to poor outcomes associated with extrahepatic symptoms. The purposes of this study were to clarify the current clinical and molecular features of hepatocerebral MTDPS and to evaluate the outcomes of LT in MTDPS patients in Japan., Results: We retrospectively assessed the clinical and genetic findings, as well as the clinical courses, of 23 hepatocerebral MTDPS patients from a pool of 999 patients who were diagnosed with mitochondrial diseases between 2007 and 2019. Causative genes were identified in 18 of 23 patients: MPV17 (n = 13), DGUOK (n = 3), POLG (n = 1), and MICOS13 (n = 1). Eight MPV17-deficient patients harbored c.451dupC and all three DGUOK-deficient patients harbored c.143-307&#95;170del335. The most common initial manifestation was failure to thrive (n = 13, 56.5%). The most frequent liver symptom was cholestasis (n = 21, 91.3%). LT was performed on 12 patients, including nine MPV17-deficient and two DGUOK-deficient patients. Among the 12 transplanted patients, five, including one with mild intellectual disability, survived; while seven who had remarkable neurological symptoms before LT died. Five of the MPV17-deficient survivors had either c.149G > A or c.293C > T., Conclusions: MPV17 was the most common genetic cause of hepatocerebral MTDPS. The outcome of LT for MTDPS was not favorable, as previously reported, however, patients harboring MPV17 mutations associated with mild phenotypes such as c.149G > A or c.293C > T, and exhibiting no marked neurologic manifestations before LT, had a better prognosis after LT.

Background and Aim: Endoscopic diagnosis of advanced histology in colorectal lesions sized <10 mm is essential for appropriate selection of resection methods. The Japan Narrow-band imaging Expert Team (JNET) classification has been recently validated for the evaluation of colorectal lesions. Our objective was to investigate the diagnostic value of the JNET classification for advanced histology in colorectal lesions sized <10 mm., Methods: We enrolled 680 patients with 1472 colorectal lesions sized <10 mm diagnosed according to the JNET classification and who subsequently underwent endoscopic or surgical resection between January and December 2017. We retrospectively examined the relationship between the JNET findings and pathological histology. Multivariate analysis was carried out to assess the predictive power of the JNET findings and clinical characteristics of lesions., Results: Advanced histology was present in 29 (2.0%) lesions. Advanced histology was absent in 68 lesions diagnosed as JNET type 1, whereas 1389 lesions diagnosed as JNET type 2A included 19 lesions of advanced histology (1.4%) with high-grade dysplasia alone. Eleven lesions diagnosed as JNET type 2B comprised eight lesions of advanced histology (72.7%) with four high-grade dysplasia and four submucosal invasive cancer, and two lesions diagnosed as JNET type 3 were submucosal invasive cancer. Multivariate analysis showed that JNET type 2B + 3 was a stronger predictive factor for advanced histology than other clinical risk factors., Conclusion: Narrow-band imaging with magnification according to the JNET classification may be a useful modality for identification of advanced histology in colorectal lesions sized <10 mm., (© 2019 Japan Gastroenterological Endoscopy Society.)

This study investigated young Japanese adults' attitudes toward suicide and factors affecting them. Results revealed that 28.78% of respondents had serious suicidal ideation history; 18.53% knew suicidal others; and 15.29% took suicide-prevention training. A t-test showed that respondents' "Right to suicide" and "Common occurrence" scores were higher with suicidal ideation history, but "Unjustified behavior" was lower than in those without history. Results indicated that certain young adults were unsupportive by being permissive of suicide due to their suicidal ideation or becoming bystanders due to inexperience. For young Japanese adults, enhancing preventive education to alter permissive/bystander attitudes is crucial., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Although differences in the incidence of chronic graft-versus-host disease (GVHD) across the races have been suggested, these have not been systematically investigated. This study compared the incidence, sites, severity, and outcomes of late acute GVHD and chronic GVHD according to National Institutes of Health (NIH) consensus criteria between Japanese (n = 413) and white (n = 708) patients after first allogeneic hematopoietic cell transplantation. Analysis was stratified according to bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT). Japanese patients, compared with white patients, had a similar incidence of late acute GVHD (BMT, 19% vs 16%; PBSCT, 19% vs 16%) but experienced more frequent liver late acute GVHD as defined by transaminase elevation (BMT, 79% vs 8%; PBSCT, 92% vs 33%) and less frequent gastrointestinal late acute GVHD (BMT, 11% vs 58%; PBSCT, 20% vs 68%). Japanese patients were more likely to discontinue systemic immunosuppression after late acute GVHD than white patients (hazard ratio, 3.68; 95% confidence interval, 1.96-6.94; P < .001). Japanese patients, compared with white patients, had a lower incidence of chronic GVHD (BMT, 15% vs 30% [ P = .002]; PBSCT, 37% vs 45% [ P < .001]) and experienced more frequent chronic GVHD of the mouth, eyes, and liver and less frequent gastrointestinal chronic GVHD. The duration of immunosuppressive treatment of NIH chronic GVHD was similar between the races. These differences could not be entirely attributed to practice variation between the centers. This study shows that the incidence, affected sites, severity, and clinical outcomes of late acute GVHD and NIH chronic GVHD differ between Japanese and white patients., (© 2019 by The American Society of Hematology.)

Background: Atrial fibrillation (AF) is the most common type of arrhythmia. The definition of AF in patients with cardiac implantable electronic devices (CIEDs) is not clear, and the appropriate treatment guideline for patients with episodes of AF has not been established yet. Additionally, little is known about the incidence of AF and embolic stroke events in Japanese patients with CIEDs. The purposes of this study were to identify the incidence of embolic stroke events in Japanese patients with and without AF events detected by CIEDs and to examine the risk factors of embolic stroke events., Methods: We retrospectively analyzed the database of our CIED clinic. Every 6 months, episodes of AF were checked by CIEDs. Using univariate (Student's t-test and Fisher's exact test) and multivariate analyses, we examined the characteristics and incidence of embolic stroke events and investigated the relationship between episodes of AF and the incidence of embolic stroke events., Results: In this study, we enrolled 348 consecutive patients who had no prior history of AF and were not administering anticoagulants (follow-up period, 65±58 months; age, 70±16 years; male sex, 64%; implantable cardioverter defibrillator, 55%). The mean CHADS 2 and CHA 2 DS 2 -VASc scores were 1.7±1.1 and 2.8±1.5 points, respectively. Fifty-five patients (16%) had AF events detected by CIEDs that lasted for ≥30s, and 23 patients (6.6%) had embolic stroke during the follow-up period. Multivariate analysis demonstrated that independent predictors for embolic stroke were a left atrial diameter ≥40mm [odds ratio (OR) 3.1, 95% confidence interval (CI) 1.2-7.9, p=0.016] and episodes of AF (OR 5.3, 95% CI 2.2-13, p=0.0003)., Conclusions: Embolic stroke events are common in Japanese patients with CIEDs. AF events lasting ≥30s and an enlarged left atrium are the risk factors of embolic stroke in this population., (Copyright © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Objectives: This study sought to assess the safety and long-term efficacy of drug-coated balloons (DCB) following aggressive intracoronary image-guided rotational atherectomy (iRA) for severe coronary artery calcification (CAC), and to compare this strategy with new generation drug-eluting stents (nDES) following iRA., Background: Ischemic events following the treatment of CAC is still relatively high. Thus, more innovative strategies are required., Methods: We evaluated 123 consecutive patients (166 lesions) with de novo CAC undergoing an iRA (burr size; 0.7 of the mean reference diameter by intracoronary imaging) followed by DCB (DCB-iRA; 54 patients, 68 lesions) or nDES (nDES-iRA; 69 patients, 98 lesions). Follow-up angiography was obtained at > 6 months., Results: The target vessels (right coronary and circumflex), bifurcation (67.6% versus 47.9%), reference diameter (2.28mm versus 2.49mm), and lesion length (11.89mm versus 18.78mm) were significantly different between the two groups. The median follow-up was 732 days. TLR and TVR in DCB-iRA and nDES-iRA at 3 years were similar: 15.6% versus 16.3% ( P =0.99) and 15.6% versus 23.3% ( P =0.38). In 41 well-matched lesion pairs after propensity score analysis, the cumulative incidence of TLR and TVR in DCB-iRA and nDES-iRA at 3 years was 12.9% versus 16.3% (P=0.70) and 12.9% versus 26.1% (P=0.17), respectively. On QCA analysis, although the acute gain was smaller in DCB-iRA (0.85 mm versus 1.53 mm, P<0.001), the minimum lumen diameter at follow-up was similar (1.69 mm versus 1.87 mm, P=0.29). The late lumen loss was lower (0.09 mm versus 0.52 mm, P=0.009) in DCB-iRA., Conclusions: DCB-iRA is feasible for CAC., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2019 Katsumi Ueno et al.)

To characterize the incidences and outcomes of late acute (LA) and chronic graft-versus-host disease (GVHD) in East Asians according to the 2014 National Institutes of Health criteria, we retrospectively analyzed 506 consecutive Japanese patients who had a first allogeneic hematopoietic cell transplantation (HCT) at our center between 2006 and 2013. According to manifestations at onset 91 patients (60%) had LA GVHD and 60 (40%) had chronic GVHD. The cumulative incidences of LA and chronic GVHD were 20% and 17%, respectively, at 48 months after HCT. The involved sites at the onset of LA GVHD included the skin (71%), gut (13%), and liver (8%). The cumulative incidences of relapse, nonrelapse mortality (NRM), transition to chronic GVHD, and discontinued systemic treatment were 11%, 6%, 22%, and 46%, respectively, at 48 months after onset of LA GVHD. Cox models showed that prior acute GVHD was associated with NRM, and HCT from a female donor to a male patient, myeloablative conditioning, and low Karnofsky performance status were associated with a longer duration of systemic treatment after LA GVHD. The most frequently involved sites at the onset of chronic GVHD included the mouth (83%), liver (75%), skin (69%), and eyes (62%). Cox models showed that use of antithymocyte globulin in conditioning regimens was associated with a higher risk of discontinued systemic treatment after the onset of chronic GVHD. The cumulative incidences of relapse, NRM, and discontinued systemic treatment were 16%, 11%, and 41%, respectively, at 48 months after the onset of chronic GVHD. Our results suggested several potential differences between Japanese patients and those of other ethnicities. A direct comparison is needed to formally investigate ethnic differences., (Copyright © 2018. Published by Elsevier Inc.)

Background: It remains controversial whether coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) should be optimized to treat coronary artery disease in patients on chronic hemodialysis (HD). Recently, further refinement of drug-eluting stents, such as the everolimus-eluting stent (EES), has led to marked development in this field. We compared long-term clinical outcomes after CABG versus PCI with EES implantation in patients on chronic HD., Patients and Methods: We compared 138 patients undergoing CABG and 187 patients treated with EES implantation. The endpoint was major adverse cardiac events (MACE) as a composite outcome, including any revascularization, nonfatal myocardial infarction, or mortality. To reduce the selection bias for the two procedures, propensity score-matching was performed., Results: During the follow-up period (43 months), 95 (29.2%) MACEs, including 43 (13.2%) revascularizations, 14 (4.3%) nonfatal myocardial infarctions, and 63 (19.4%) deaths, occurred. The freedom rate from MACE and mortality at 5 years were comparable between groups (69.7 vs. 66.7%, P=0.82 and 75.0 vs. 80.6%, P=0.10, respectively); however, those from revascularization at 5 years was higher in the CABG group than the EES group (89.4 vs. 81.0%, P=0.030). In propensity score-matched patients (n=92), the freedom rate from revascularization at 5 years was still higher in the CABG group than in the EES group (93.4 vs. 79.1%, P=0.013). Similarly, the freedom rates from MACE and mortality were comparable (70.0 vs. 66.3%, P=0.69 and 73.8 vs. 79.7%, P=0.30, respectively)., Conclusion: Even in the second-generation drug-eluting stent era, CABG is still superior for preventing revascularization in patients on chronic HD. However, PCI with EES implantation might not have disadvantages compared with CABG in terms of MACE.

The first clinical case of the YG1 strain of the severe fever with thrombocytopenia syndrome virus (SFTSV) has been isolated in Japan. We found that only some of the cells underwent low pH-dependent cell fusion, although all of the cells were confirmed to have been infected with the virus. This suggested that the YG1 strain consists of a heterogeneous mixture of related viruses. Here, we established 3 subclones (termed E3, A4, and B7) from the YG1 strain, using the limiting dilution method with the pH-dependent cell fusion activity. Subclone E3 showed weak fusion activity and cytopathic effects (CPE) in Vero E6 cells. The amino acid sequence of E3 was identical to the published sequence for the YG1 strain, and it likely comprises a subpopulation of the YG1 strain. Subclone A4 displayed strong fusion activity under acidic conditions. In contrast, subclone B7 showed strong fusion activity and CPE under neutral and acidic conditions. Two amino acid differences shared between B7 and A4 were found in the envelope glycoproteins. In addition, an amino acid variant of the RNA-dependent RNA polymerase was found only in B7. These subclones will be valuable tools to elucidate cell fusion mechanisms of SFTSV and the relationship between viral proteins and their functions.

Objective: Increasing evidence has suggested a protective role of vitamin D on metabolic syndrome (MetS). However, studies addressing this issue are limited in Asia and it remains unclear whether calcium could modify the association. We examined the association of serum 25-hydroxyvitamin D (25(OH)D) status with MetS, and the potential effect modification by calcium intake in a Japanese working population., Methods: Study subjects were 1790 workers, ages 18 to 69 y, who participated in a health survey at the time of periodic checkup. MetS was defined according to the joint interim statement. Serum 25(OH)D was measured by a protein binding assay. Multilevel logistic regression was used to estimate the odds ratio (OR) with adjustment for potential confounding variables., Results: An inverse trend was observed between 25(OH)D and MetS. Compared with those with a 25(OH)D of <20 ng/mL, multivariable adjusted OR (95% confidence interval) for MetS was 0.79 (0.55-1.15) and 0.52 (0.25-1.04) for those with a 25(OH)D of 20 to 29 ng/mL and ≥30 ng/mL, respectively (P for trend = 0.051). Similar association was observed in the analysis using quartile categories of 25(OH)D; the OR in the highest quartile of 25(OH)D compared with the lowest quartile was 0.61 (0.36-1.01) (P for trend = 0.046). This association was noted only in older subjects (≥44 y). The inverse association between serum 25(OH)D and MetS was more pronounced in subjects with high calcium intake. The inverse association between 25(OH)D and MetS appears to be linear according to restricted cubic spline regression. There was inverse, but statistically nonsignificant, associations between 25(OH)D and each component of MetS., Conclusion: Our results suggest that higher circulating vitamin D is associated with decreased likelihood of having MetS among Japanese adults., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Dietary fiber may play a favorable role in mood through gut microbiota, but epidemiologic evidence linking mood to dietary fiber intake is scarce in free-living populations. We investigated cross-sectionally the associations of dietary intakes of total, soluble, insoluble, and sources of fiber with depressive symptoms among Japanese workers., Methods: Participants were 1977 employees ages 19-69 y. Dietary intake was assessed via a validated, brief self-administered diet history questionnaire. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Logistic regression was used to estimate odds ratios of depressive symptoms adjusted for a range of dietary and non-dietary potential confounders., Results: Dietary fiber intake from vegetables and fruits was significantly inversely associated with depressive symptoms. The multivariable-adjusted odds ratios (95% confidence intervals) for the lowest through the highest tertile of vegetable and fruit fiber were 1.00 (reference), 0.80 (0.60-1.05), and 0.65 (0.45-0.95), respectively (P for trend = 0.03). Dietary intake of total, soluble, insoluble, and cereal fiber was not associated with depressive symptoms., Conclusions: Higher dietary fiber intake from vegetables and fruits may be associated with lower likelihood of having depressive symptoms., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: To ascertain a molecular genetic diagnosis for subjects with neonatal/infantile intrahepatic cholestasis (NIIC) by the use of next-generation sequencing (NGS) and to perform a genotype-phenotype correlation., Study Design: We recruited Japanese subjects with NIIC who had no definitive molecular genetic diagnosis. We developed a diagnostic custom panel of 18 genes, and the amplicon library was sequenced via NGS. We then compared clinical data between the molecular genetically confirmed subjects with NIIC., Results: We analyzed 109 patients with NIIC ("genetic cholestasis," 31 subjects; "unknown with complications" such as prematurity, 46 subjects; "unknown without complications," 32 subjects), and a molecular genetic diagnosis was made for 28 subjects (26%). The rate of positive molecular genetic diagnosis in each category was 22 of 31 (71%) for the "genetic cholestasis" group, 2 of 46 (4.3%) for the "unknown with complications" group, and 4 of 32 (12.5%) for the "unknown without complications" group. The grouping of the molecular diagnoses in the group with genetic cholestasis was as follows: 12 with Alagille syndrome, 5 with neonatal Dubin-Johnson syndrome, 5 with neonatal intrahepatic cholestasis caused by citrin deficiency, and 6 with progressive familial intrahepatic cholestasis or benign recurrent intrahepatic cholestasis with low gamma-glutamyl transpeptidase levels. Several clinical datasets, including age of onset, direct bilirubin, and aminotransferases, were significantly different between the disorders confirmed using molecular genetic diagnosis., Conclusion: Targeted NGS can be used for molecular genetic diagnosis in subjects with NIIC. Clinical diagnosis should be accordingly redefined in the view of molecular genetic findings., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The purpose of this study was to describe the beliefs of Japanese mothers caring for a child with disabilities to advance knowledge about beliefs of Japanese families experiencing illness. A semistructured interview was conducted with eight mothers who had a child with disabilities (physical, intellectual, and/or developmental). The interview invited their reflections about "mutual thoughts of family members" and family relationships in the context of daily life of caring for a child with disabilities. Data were qualitatively analyzed inductively and deductively and compared with the Common Tentative Framework of Japanese Family Beliefs developed from previous research. The analyses highlighted new understandings of the influence of Japanese cultural and societal beliefs on the family's experience of having a child with disabilities. Clinical implications are discussed and directions for future research suggested., (© The Author(s) 2015.)

Objective: Although intake of minerals has been suggested to be beneficial against depression, epidemiologic data from free-living settings are limited. The aim of this study was to determine the cross-sectional associations between the intake of magnesium, calcium, iron, and zinc and the prevalence of depressive symptoms in Japanese employees., Methods: Participants were 1792 men and 214 women ages 19 to 69 y. Dietary intake was assessed using a validated, brief self-administered diet history questionnaire. Participants with depressive symptoms were defined as those with a scale score of ≥16 on the Center for Epidemiologic Studies Depression Scale., Results: The prevalence of depressive symptoms was 27.8%. Intakes of magnesium, calcium, iron, and zinc were inversely associated with the prevalence of depressive symptoms. The multivariate adjusted odds ratios (95% confidence interval) of having depressive symptoms were 0.63 (0.44-0.91), 0.64 (0.47-0.88), 0.59 (0.40-0.87), and 0.63 (0.45-0.87) in the highest versus lowest tertiles of magnesium, calcium, iron, and zinc, respectively., Conclusion: Results suggest that higher dietary intake of magnesium, calcium, iron, and zinc is associated with lower prevalence of depressive symptoms in Japanese employees., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Some important virulence factors have been elucidated in Klebsiella pneumoniae infections. We investigated the relationship between virulence factors and multilocus sequence types (STs) and assessed the risk factors for bacteremia in patients with pneumonia due to K. pneumoniae. From April 2004 through April 2012, a total of 120 K. pneumoniae isolates from patients with pneumonia (23 with bacteremia and 97 without bacteremia) were collected from 10 medical institutions in Japan. Additionally, 10 strains of K. pneumoniae serotype K2 that were isolated >30 years ago were included in this study. These isolates were characterized using multilocus sequence typing (MLST), and the characteristics of their virulence factors, such as hypermucoviscosity phenotype and RmpA and aerobactin production between patients with and without bacteremia, were examined. MLST analysis was performed on the 120 isolates from patients with pneumonia, and some sequence type groups were defined as genetic lineages (GLs). GL65 was more prevalent among patients with bacteremia (21.7%) than in those without bacteremia (7.2%). The majority of the strains with serotype K2 were classified into GL14 or GL65, and rmpA and the gene for aerobactin were present in all GL65-K2 strains but absent in all GL14-K2 strains. In a multivariate analysis, the independent risk factors for bacteremia included GL65 (adjusted odds ratio [AOR], 9.46; 95% confidence interval [CI], 1.81 to 49.31), as well as neoplastic disease (AOR, 9.94; 95% CI, 2.61 to 37.92), immunosuppression (AOR, 17.85; 95% CI, 1.49 to 214.17), and hypoalbuminemia (AOR, 4.76; 95% CI, 1.29 to 17.61). GL65 was more prevalent among patients with bacteremia and was associated with the virulence factors of K. pneumoniae., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Background: Accumulating evidence suggests a protective role of vitamin D against mood disorders; however, epidemiologic studies are scarce in working populations., Objective: We investigated cross-sectionally the association of serum vitamin D status and depressive symptoms among Japanese workers., Methods: Participants were 1786 employees (9% women), aged 19-69 y, who received health check-ups and participated in a nutrition and health survey. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured with the use of a competitive protein binding assay. Depressive symptoms were assessed by using the Center for Epidemiologic Studies Depression (CES-D) scale. Logistic regression was used to estimate ORs with adjustment for potential confounding variables including dietary factors., Results: Overall, 92% of study participants had suboptimal vitamin D status [25(OH)D <30 μg/L]. Depressive symptoms were inversely associated with 25(OH)D. Compared with those with a 25(OH)D concentration of <20 μg/L, multivariable-adjusted ORs (95% CIs) for depressive symptoms (CES-D scale score ≥16) were 0.75 (0.59, 0.95) and 0.66 (0.41, 1.06) for those with a 25(OH)D concentration of 20-29 μg/L and ≥30 μg/L, respectively (P-trend = 0.01). After further adjustment for leisure-time physical activity and shift work (factors closely related to photo-initiated vitamin D production), the OR (95% CI) for the highest category of 25(OH)D was 0.70 (0.43, 1.14). The association between 25(OH)D and depressive symptoms appears to be linear, according to restricted cubic spline regression., Conclusion: Results suggest that lower concentrations of circulating vitamin D are associated with increased likelihood of having depressive symptoms among apparently healthy workers., (© 2015 American Society for Nutrition.)

Objective: Experimental studies have shown that some nutrients are involved in initiating and maintaining sleep, but epidemiological evidence on overall dietary patterns and insomnia is scarce. We investigated the relationship between dietary patterns and sleep symptoms in a Japanese working population., Methods: The participants were 2025 workers, aged 18-70 years, who participated in a health survey during a periodic checkup in 2012 and 2013. Dietary intake was assessed with a self-administered diet history questionnaire. Dietary patterns were extracted by principal component analysis on the basis of the energy-adjusted intake of 52 food and beverage items. Sleep duration, difficulty initiating and maintaining sleep, and poor quality of sleep were self-reported. Logistic regression was used to estimate the odds ratios of each sleep symptom according to quartile categories of each dietary pattern with adjustment for potential confounding variables., Results: We identified three major dietary patterns. A healthy pattern, characterized by a high intake of vegetables, mushrooms, potatoes, seaweeds, soy products, and eggs, was associated with a decreased prevalence of difficulty initiating sleep once or more a week (P for trend = 0.03); the multivariate adjusted odds ratio in the highest quartile of this score compared with the lowest was 0.75 (95% CI: 0.57-0.99). This association persisted after the exclusion of individuals with severe depressive symptoms. However, there was no significant association with difficulty initiating sleep at least three times a week., Conclusions: Our findings suggest that a healthy dietary pattern may be associated with difficulty initiating sleep at least once a week., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: Acid-base status has been suggested to influence blood pressure, but there is a paucity of epidemiologic evidence linking dietary acid load to hypertension. We examined cross-sectionally the association between dietary acid load and hypertension in a Japanese working population., Methods: Data were derived from health surveys from 2028 employees, ages 18 to 70 y, in two workplaces in Japan. A validated brief diet history questionnaire was used to assess diet. Two measures were used to characterize dietary acid load: potential renal acid load and estimated net endogenous acid production, which were derived from nutrient intakes. Multilevel logistic regression was used to examine the association between dietary acid load and hypertension with adjustment of potential confounding variables., Results: High dietary acid load was suggestively associated with increased prevalence of hypertension. The multivariable adjusted odds ratios (95% confidence interval) of hypertension for the lowest through highest tertiles of net endogenous acid production were 1.00 (reference), 1.07 (0.80-1.42), and 1.33 (0.998-1.78), respectively (P for trend = 0.053). This positive association was statistically significant among normal-weight (body mass index <23 kg/m(2); P for trend = 0.03) and non-shift workers (P for trend = 0.04). Similar positive associations were observed between potential renal acid load and hypertension., Conclusions: The present findings suggest that high dietary acid load may be associated with increased prevalence of hypertension among those who were normal weight and non-shift workers., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The aim of this study is to determine which indicator of chronic kidney disease most closely correlates with 10-year Framingham coronary heart disease (CHD) risk among serum creatinine, serum cystatin C (S-CysC), urine albumin-creatinine ratio (UACR), estimated creatinine-based GFRs (eGFRcre), and estimated CysC-based GFRs (eGFRcys) in patients with obesity and diabetes. Serum creatinine, S-CysC, UACR, and cardio-ankle vascular index (CAVI) were examined in 468 outpatients with obesity and type 2 diabetes, free of severe renal dysfunction or previous history of cardiovascular disease, as a cross-sectional survey using baseline data from the multi-centered Japan Diabetes and Obesity Study. S-CysC and eGFRcys had significantly stronger correlations with the 10-year Framingham CHD risk than serum creatinine, eGFRcre, and UACR (creatinine, ρ = 0.318; S-CysC, ρ = 0.497; UACR, ρ = 0.174; eGFRcre, ρ = -0.291; eGFRcys, ρ = -0.521; P < 0.01 by Fisher's z-test). S-CysC and eGFRcys had significantly stronger correlations with CAVI than serum creatinine, eGFRcre, and UACR (creatinine, ρ = 0.198; S-CysC, ρ = 0.383; UACR, ρ = 0.183; eGFRcre, ρ = -0.302; eGFRcys, ρ = -0.444; P < 0.05 by Fisher's z-test). The receiver operating characteristic curves to distinguish the high-risk patients for CHD revealed significantly larger areas under the curve of S-CysC and eGFRcys than those of serum creatinine, UACR, and eGFRcre (serum creatinine, 0.64; S-CysC, 0.75; UACR, 0.56; eGFRcre, 0.63; eGFRcys, 0.76; P < 0.01). The data suggested that eGFRcys can be more predictive of the 10-year CHD risk than eGFRcre in Japanese patients with obesity and diabetes.

The tick is a well-known vector for arthropod-borne pathogens, such as tick-borne encephalitis, Lyme disease, Japanese spotted fever and severe fever with thrombocytopenia syndrome. It is therefore important to know the tick population and distribution in our environment and wild animals in order to prevent tick-borne diseases. Here, we report the results of tick surveillance from May to September 2011 at 14 geographical points and in 5 wild boars in Kyoto City, Kyoto prefecture, Japan. We collected 3,198 ticks comprising 5 tick species, Haemaphysalis (H.) longicornis, H. flava, H. kitaokai, Amblyomma testudinarium and Dermacentor taiwanensis. Interestingly, the proportion of tick species varied according to geographical region within the city. The ticks collected in the city were reported as potential vectors of pathogens, such as rickettsiosis. We detected rickettsial DNA by PCR in 71.1% of 201 ticks investigated. The ticks that carried rickettsiae were distributed across the whole the city. The sequences of PCR-amplified DNA fragments were determined and showed similarities to spotted fever group rickettsiae. Although their pathogenicity for animals including humans is still unclear, it is important to stay alert and pay attention to tick-borne diseases in order to ensure the safety of the citizens of the city as well as that of visitors.

This study was aimed to examine the cross-sectional association of protein, carbohydrate, and fat intake with depressive symptoms among 1794 Japanese male workers aged 18-69 years who participated in a health survey. Dietary intake was assessed with a validated self-administered diet history questionnaire. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. Odds ratio of depressive symptoms (CES-D scale of ≥16) was estimated by using multiple logistic regression with adjustment for covariates including folate, vitamin B6, vitamin B12, polyunsaturated fatty acid, magnesium, and iron intake. Multivariable-adjusted odds ratio of depressive symptoms for the highest quartile of protein intake was 26%, albeit not statistically significant, lower compared with the lowest. The inverse association was more evident when a cutoff value of CES-D score ≥19 was used. The multivariable-adjusted odds ratios (95% confidence intervals) for the highest through lowest quartile of protein intake were 1.00 (reference), 0.69 (0.47-1.01), 0.69 (0.44-1.09), and 0.58 (0.31-1.06) (P for trend=0.096). Neither carbohydrate nor fat intake was associated with depressive symptoms. Our findings suggest that low protein intake may be associated with higher prevalence of depressive symptoms in Japanese male workers., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Rationale: Identification of patients with drug-resistant pathogens at initial diagnosis is essential for treatment of pneumonia., Objectives: To elucidate clinical features of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP), and to clarify risk factors for drug-resistant pathogens in patients with CAP and HCAP., Methods: A prospective observational study was conducted in hospitalized patients with pneumonia at 10 institutions in Japan. Pathogens identified as not susceptible to ceftriaxone, ampicillin-sulbactam, macrolides, and respiratory fluoroquinolones were defined as CAP drug-resistant pathogens (CAP-DRPs)., Measurements and Main Results: In total, 1,413 patients (887 CAP and 526 HCAP) were analyzed. CAP-DRPs were more frequently found in patients with HCAP (26.6%) than in patients with CAP (8.6%). Independent risk factors for CAP-DRPs were almost identical in patients with CAP and HCAP. These included prior hospitalization (adjusted odds ratio [AOR], 2.06; 95% confidence interval [CI], 1.23-3.43), immunosuppression (AOR, 2.31; 95% CI, 1.05-5.11), previous antibiotic use (AOR, 2.45; 95% CI, 1.51-3.98), use of gastric acid-suppressive agents (AOR, 2.22; 95% CI, 1.39-3.57), tube feeding (AOR, 2.43; 95% CI, 1.18-5.00), and nonambulatory status (AOR, 2.45; 95% CI, 1.40-4.30) in the combined patients with CAP and HCAP. The area under the receiver operating characteristic curve for counting the number of risk factors was 0.79 (95% CI, 0.74-0.84)., Conclusions: The clinical profile of HCAP was different from that of CAP. However, physicians can predict drug resistance in patients with either CAP or HCAP by taking account of the cumulative number of the risk factors. Clinical trial registered with https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000004001&language=E ; number UMIN000003306.

Background/aims: Type B and C hepatic cirrhosis are main causes of hepatocellular carcinoma (HCC). In resected cases of HCC, residual liver function of type B cirrhotic patients tend to be better compared to type C cirrhotic patients. We compared clinical data of patients with type B hepatic cirrhosis with type C hepatic cirrhosis who underwent hepatic resection for HCC., Methodology: Subjects were 16 patients with type B hepatic cirrhosis and 20 patients with type C hepatic cirrhosis who underwent hepatic resection for HCC at Jikei University Hospital. Perioperative findings including age, gender, preoperative laboratory data including ICGR15, Child's classification, model for end-stage liver disease (MELD) score, tumor factor, type of resection, duration of operation, blood loss and incidence of post-operative complications, as well as disease-free and overall survival were analyzed., Results: In type B cirrhotic patients, the age was younger (p<0.001), pre-operative ICGR15 (p=0.004), hemoglobin (p=0.032), albumin (p=0.006), Child's classification (p=0.008), and MELD score (p=0.011) were better, and incidence of postoperative pulmonary complications were fewer (p=0.039) than type C cirrhotic patients. Preoperative ICG, in 11 of 16 type B cirrhotic patients were normal (<10%)., Conclusions: Residual liver function of type B cirrhotic patients were better than type C cirrhotic patients.

Objectives: To determine the characteristics of health behaviors related to higher-level functional decline in older community-dwelling adults., Design: Prospective., Setting: Ohasama Town, Japan., Participants: One thousand fifty residents (mean age: 67.5) free of functional decline at baseline., Measurements: Health behaviors including smoking status, alcohol consumption, frequency of exercise, sleep duration, dietary habits (supplement use, breakfast, late-night snacking, eating regularly, and eating out), and self-rated health were obtained from a self-administered questionnaire at baseline. Higher-level functional decline was examined using the subscales of the Tokyo Metropolitan Institute of Gerontology Index of Competence., Results: During the 7-year follow-up, 27.5% of eligible participants reported decline in higher-level functional capacity. After adjustment for putative confounding factors, health behaviors that were significant predictors for declines in higher-level functional capacity at the 7-year follow-up were current smoking (odds ratio (OR) = 1.58, 95% confidence interval (CI) = 1.06-2.36), sleep duration of 9 hours or longer (OR = 2.15, 95% CI = 1.49-3.11), and poor self-rated health (OR = 1.93, 95% CI = 1.40-2.67)., Conclusion: Several modifiable health behaviors contribute to higher-level functional decline., (© 2011, Copyright the Authors Journal compilation © 2011, The American Geriatrics Society.)

Background: In March 2009, pandemic influenza A(H1N1) (A(H1N1)pdm) emerged in Mexico and the United States. In Japan, since the first outbreak of A(H1N1)pdm in Osaka and Hyogo Prefectures occurred in the middle of May 2009, the virus had spread over 16 of 47 prefectures as of June 4, 2009., Methods/principal Findings: We analyzed all-segment concatenated genome sequences of 75 isolates of A(H1N1)pdm viruses in Japan, and compared them with 163 full-genome sequences in the world. Two analyzing methods, distance-based and Bayesian coalescent MCMC inferences were adopted to elucidate an evolutionary relationship of the viruses in the world and Japan. Regardless of the method, the viruses in the world were classified into four distinct clusters with a few exceptions. Cluster 1 was originated earlier than cluster 2, while cluster 2 was more widely spread around the world. The other two clusters (clusters 1.2 and 1.3) were suggested to be distinct reassortants with different types of segment assortments. The viruses in Japan seemed to be a multiple origin, which were derived from approximately 28 transported cases. Twelve cases were associated with monophyletic groups consisting of Japanese viruses, which were referred to as micro-clade. While most of the micro-clades belonged to the cluster 2, the clade of the first cases of infection in Japan originated from cluster 1.2. Micro-clades of Osaka/Kobe and the Fukuoka cases, both of which were school-wide outbreaks, were eradicated. Time of most recent common ancestor (tMRCA) for each micro-clade demonstrated that some distinct viruses were transmitted in Japan between late May and early June, 2009, and appeared to spread nation-wide throughout summer., Conclusions: Our results suggest that many viruses were transmitted from abroad in late May 2009 irrespective of preventive actions against the pandemic influenza, and that the influenza A(H1N1)pdm had become a pandemic stage in June 2009 in Japan.

We analyzed the antibiotic resistant genes, metallo-beta-lactamase and extended-spectrum beta-lactamase (ESBL), in highly resistant Enterobacter cloacae isolated at Showa University Hospital from April to June 2008. Thirty eight strains of E. cloacae were isolated. Of these strains, 35 demonstrating resistant to either cefotaxime (Minimum inhibitory concentration: MIC > or = 32 microg/ml), ceftadizime (MIC > or = 16 microg/ml), or aztreonam (MIC > or = 16 microg/ml) were selected for the analysis. The strains were subjected to a Double-disk synergy test (DDST) using sodium mercaptoacetic acid (SMA) and ceftadizime. As a result, 7 strains showed an enlargement of inhibition zone diameter by SMA. Among 7 SMA responded strains, 6 strains carried the bla(IMP-1) or bla(IMP-11) gene. There were 2 strains sensitive to imipenem (MIC < 1 microg/ml) in SMA responded strains, and one carried bla(IMP-11) gene. ESBL genes were detected in 5 strains, bla(CTX-M3) gene from 3 strains, and bla(CTX-M14) gene from 2 strains. All of the ESBL harboring strains showed an enlargement of inhibition zone diameter in DDST using clavulanic acid and ceftadizime, cefotaxime, aztreonam or cefepime. Among 35 strains, one strain carried both bla(IMP-1) and bla(CTX-M3) genes. In addition to the AmpC beta-lactamase, increase of the E. cloacae strains carrying these resistant genes cause the complex antibiotic resistant patterns. Especially, strains carrying bla(IMP) gene, which exhibit low imipenem MIC value may be induced to be resistant strains under the existence of imipenem. Analysis of resistant genes would be a beneficial for the measure the spread of drug-resistant E. cloacae.

We previously reported identifying SOX6 as a glioma antigen by serological screening using a testis cDNA library. Its preferential expression and frequent IgG responses in glioma patients indicate that SOX6 may be a useful target for immunotherapy. To examine whether cytotoxic T-lymphocyte (CTL) responses specific for SOX6 to destroy glioma can be generated in vivo, we treated glioma-bearing mice by vaccination with a plasmid DNA encoding murine full-length SOX6 protein. Following SOX6-DNA vaccination, CTLs specific for SOX6-expressing glioma cells were induced, while normal autologous-cells that had restrictedly expressed SOX6 during embryogenesis were not destroyed. Furthermore, DNA vaccination with SOX6 exerted protective and therapeutic antitumor responses in the glioma-bearing mice. This antitumor activity was abrogated by the depletion of CD4 positive T cells and/or CD8 positive T cells. These results suggest that the SOX6 protein has multiple CTL and helper epitopes to induce antitumor activity and the effectiveness of SOX6-DNA vaccine for the prevention and treatment of glioma., ((c) 2008 Wiley-Liss, Inc.)

Background/aims: Pancreatic intraepithelial neoplasms (PanINs) have been considered as age-related lesions as well as precancerous lesions. However, we do not know their true relationship with age because the former studies did not deal with all age groups. Moreover, the numbers of the patients in each age group were not the same. This study was done to examine the "true relationship" between PanINs and age., Methodology: Ninety autopsied normal appearing pancreases from all age groups (from under 10s to 80s) were examined. Each group had 10 patients. The relationship between PanINs and age was studied. The sexual difference was also studied., Results: Both the incidence of PanIN positive patients and the number of PanINs increased with age from under 10s to 40s, but they did not correlate with patient age after 40s. The number of PanIN positive patients in the under 10s, 40s and 80s were 2, 10 and 9, respectively. The number of PanINs in the under 10s, 40s and 80s were 11, 127 and 130, respectively. A sexual difference was not seen., Conclusions: The relationship between PanINs and age showed a biphasic correlation pattern before and after 40s. The presence of PanIN positive patients in their first year of age was also a new finding.

In papillary thyroid carcinogenesis, the constitutively activated mitogen-activated protein (MAP) kinase signaling pathway caused by a genetic alteration such as RET/PTC rearrangement or mutation of RAS and BRAF genes, is thought to be a major early event. Among these, the recently identified BRAF(V600E) mutation has been found at high frequency in adult patients with papillary thyroid carcinoma (PTC). However, the association between this mutation and radiation exposure in adult PTC is still unknown. In this study, we examined the BRAF(V600E) mutation in 64 PTCs among adult atomic bomb survivors in Hiroshima, Japan, comprising 17 nonexposed (0 mGy) and 47 exposed patients who developed the carcinoma after the bombing, and assessed the association of BRAF(V600E) mutation with clinico-pathological and epidemiological variables. The median radiation dose in PTCs with the BRAF(V600E) mutation was significantly lower than that without the mutation (18.5 vs.156.9 mGy, Wilcoxon rank-sum test, P=0.022). A significant difference was found in the median latency period (years elapsed from atomic bombing to diagnosis) between exposed patients with and without BRAF(V600E) mutation (29 vs. 21 yr, Wilcoxon rank-sum test, P=0.014). These findings were further confirmed by logistic regression analysis with BRAF(V600E) mutation status as a dependent variable and taking into account possible interactions between the variables. We found that the log-transformed radiation dose and latency period were independently associated with the BRAF(V600E) mutation (P=0.039 and P=0.010, respectively). These results suggest that involvement of BRAF mutation in thyroid carcinogenesis in exposed people may differ from that in the nonexposed people., ((c) 2006 Wiley-Liss, Inc.)

A C/A single nucleotide polymorphism (SNP) in the E-cadherin gene promoter has been shown to affect transcriptional efficiency in vitro. In this study, we analyzed the C/A SNP in 106 gastric carcinoma cases and 90 cancer-free controls compared with clinicopathological parameters. The genotype of C/C, C/A, and A/A was found in 61 (58%), 34 (32%) and 11 (10%) of 106 gastric carcinoma cases and in 32 (36%), 52 (58%) and 6 (6%) of 90 cancer-free controls, respectively. The genotype of C/C was significantly more frequent in gastric carcinoma cases than in cancer-free controls (p<0.05). The E-cadherin protein expression level in non-neoplastic gastric mucosa was higher in the C/C genotype than in the C/A. In gastric carcinoma cases, the genotype of C/C was significantly more frequent in the cases of poorly differentiated adenocarcinoma (31/44; 70%) than in well differentiated type (30/62; 48%). The C/C genotype was also significantly more frequent in the cases with deep invasion (51/74; 69%) and with lymph node metastasis (38/54; 70%) than in those confined superficially (10/32; 31%) and without lymph node metastasis (23/52; 44%), respectively (p<0.05). These results suggest that the C/A SNP in the E-cadherin promoter may be a good marker for malignancy of gastric carcinomas.

Emergence of Influenza A H1N2 viruses was documented worldwide during the 2001-2002 influenza season. In Japan, H1N2 viruses were isolated from two students of a junior high school in an influenza outbreak in Yokohama City, February 2001. Genetic and antigenic analyses demonstrated that the H1N2 viruses isolated in Japan shared common features with those isolated in other countries.

Background: Food-dependent, exercise-induced anaphylaxis (FEIAn) is classified among the physical allergies. The pathophysiology of FEIAn remains unknown, as does the frequency of FEIAn in the general population., Objective: We sought to study the epidemiology of FEIAn, especially its frequency in junior-high-school students in Yokohama, Japan., Methods: A questionnaire asking about the occurrence of FEIAn in school students was sent to all 145 public junior-high-school nurses in Yokohama., Results: One hundred thirty-two junior-high-school nurses responded to the questionnaire, and 13 (11 boys and 2 girls) cases of FEIAn among 76,229 junior-high-school students were reported. In addition, 24 (12 boys and 12 girls) subjects with exercise-induced anaphylaxis (EIAn) were detected. From this survey, the frequency of FEIAn was 0.017% in this population, and its frequency was significantly higher in boys than in girls (P < .05). The frequency of EIAn was 0.031%, and there was no difference according to sex. Only one third of junior-high-school nurses had any knowledge of FEIAn. We also performed provocation tests in 5 of the 13 cases with FEIAn after obtaining informed consent from the students and their parents and were able to confirm the diagnosis., Conclusion: This study showed that FEIAn and EIAn are relatively rare diseases among junior-high-school students in Yokohama. To avoid serious outcomes, we believe it is important that not only physicians but also school nurses and teachers of physical education be aware of these diseases.

To analyze the epidemiology of out-of-hospital cardiac arrests and to elucidate modifiable factors affecting survival, we conducted a prospective cohort study in a middle-sized urban city served by a single emergency medical service (EMS) system in which emergency medical technicians use an automated external defibrillator. Data were collected from out-of-hospital cardiac arrests occurring between 1 January, 1994 and 31 December, 1998 by applying the Utstein style. The main outcome measure was survival at 1 year after hospital discharge. The overall incidence of out-of-hospital cardiac arrest was 71.7/100 000 inhabitants/year. Resuscitations were attempted in 762 of 1118 patients with confirmed cardiac arrest. Of the 762 patients, 37 (4.86%) survived. The cause of cardiac arrest was presumed to be cardiac in 340 (44.6%). Of the 340 cardiac arrests, 180 (52.9%) were witnessed by bystanders. Ventricular fibrillation (VF) was recorded as an initial rhythm in 56 (31.1%) of the 180 patients, and cardiopulmonary resuscitation (CPR) was performed by bystanders in 89 (49.4%). The survival rate was 39.2% (22/56) when cardiac arrest was bystander-witnessed and of cardiac origin with VF as an initial rhythm. VF as an initial rhythm, age of the patients and intervals of call-to-first CPR attempt and collapse-to-arrival at patient's side were major factors relating to survival in the witnessed cardiac arrests of cardiac origin. The age, and gender of the patients, place of collapse and intervals of collapse-to-first CPR and collapse-to-arrival at patient's side were representative factors affecting the incidence of VF as an initial rhythm. The survival rate in Akita-City from bystander-witnessed cardiac arrests of cardiac origin with VF as an initial rhythm was comparable to those in other regions with advanced EMS systems. However, the incidence of VF as an initial rhythm is extremely low. Reduction of intervals of call (collapse)-to-first CPR attempt and collapse-to-arrival at patient's side or authorization of use of automated external defibrillator in basic life support may increase the incidence of VF as an initial rhythm and improve the survival from witnessed cardiac arrests with cardiac origin.