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Wearing dentures has been believed to decrease the instability of the postural sway using the total length of centre of pressure (CoP) trajectory or the magnitude of its variability. However, the physical aspects of the postural sway have not been taken into account while evaluating the CoP in patients who wear dentures. The CoP fluctuations are found to show a random walk process. Therefore, changes in the random movement of CoP caused by wearing dentures should be examined by nonlinear dynamics that enables analysis of the characteristics found in the random movement. We evaluated the effect of complete denture installation on CoP sway for twenty-six edentulous patients by performing the following steps. First, we excluded subjects who did not show crossover in spectral analyses. Then, we evaluated the spectral characteristics and phase shifts of the velocities of CoP sway for the subjects who showed crossover. We found that wearing complete dentures decreased the fluctuations in the high-frequency part of the power spectral density ( PSD) and the phase shift in the mediolateral direction. On the other hand, we also found that the use of complete dentures decreased the fluctuations of PSD amplitude in the anteroposterior direction. From the point of view of the kinetic energy of the musculoskeletal system, we suggested that the use of complete dentures could reduce the energy consumption for the standing posture. [ABSTRACT FROM AUTHOR]

Objectives: Introduction of a new grid-based method for analyzing speech functions which takes into account the related information of patients' data and the oral air flow with pronouncing analyzed by computational fluid dynamics.Methods: An on-line speech analyzer was developed for clinical use utilizing GridPort2.3.1 based on globus2.4.2, comprising several computational tools such as unified data storage, semantic data analysis, computational fluid dynamics analysis and three-dimensional visualization of calculated results from different hardware sources with various types of operation systems.Results: The power transportation layer between dental clinics and computational and storage resources could be provided by using a WWW-based portal. The backend data management system could be constructed using a storage resource broker (SRB) and extensible mark up language (XML).Conclusions: The new method allows the construction of a data warehouse through this grid-based speech function analysis in order to extract the principal factors related to speech disorders. [ABSTRACT FROM AUTHOR]

In this study, we examined the subsurface structure in the vicinity of the active Atera fault beneath at least one monogenetic volcano that forms the Sakashita body of the Ueno basalts, central Japan. Microgravity and seismic reflection surveys over an area of about 3×3 km (horizontal)×1 km (vertical from surface) revealed that (1) a low-density body interpreted as the damaged zone of the Atera fault reaches a depth more than 200 m below sea level; and (2) a weak zone of crust that may exist about 1.5 km southwest of the Atera fault in a direction parallel to it. By combining the shape of the Sakashita body and (2), we propose that a dyke extending in a NW–SE direction with several vent alignments in the same direction may exist along this weak zone. This suggests that the studied area was governed in the NW–SE compressional and NE–SW extensional stress field when the Sakashita body formed. [Copyright &y& Elsevier]

Introduction: This case study aimed to demonstrate how cooking class activities held in collaboration with the Ajinomoto Foundation (TAF) and a consumer cooperative after the Great East Japan Earthquake contributed to the resilience of the affected community., Methods: With reference to the logic model, evaluation indicators for the case study were established. We focused on the Iwate Seikatsu Kyodo Kumiai (Iwate Co-op). We organized 120 continuation cases out of the eight-and-a-half-year activity records of the project owned by TAF (April 2012 to March 2020). The Iwate Co-op was one of the 120 continuing cases and had special features, including awareness that its members were responsible for the community., Results: The collaboration revealed three effects. First, owing to the encounter and collaboration with TAF, the cooking class was continuously conducted even after TAF withdrew from the disaster-affected areas. Second, the Iwate Co-op trained some of its members as food support staff to run the cooking class independently and was actively involved in obtaining the necessary budget for the operation, consequently leading to the independent activation of member activities. Third, they developed a cooking class project in inland areas other than disaster-stricken areas, assuming that they could incorporate the project into their existing activities, as food problems affected people beyond disaster victims., Conclusion: The collaborative food support project of the Iwate Co-op and TAF contributed to the resilience of the affected people and communities by strengthening bonds and solidarity among residents and organizations. The key to success was the fusion of a traditional sense of independence in the co-op with TAF's mission and technical know-how. The partnership between the Iwate Co-op and TAF allowed the former to aim toward developing food support activities in the affected areas, accelerating the resilience of the community in the Iwate Prefecture., Competing Interests: KKo was employed by Miyako Co-op, Iwate Co-op. KN and KF were employed by Kamaishi Co-op, Iwate Co-op. KKa was employed by Kesen Co-op, Iwate Co-op. HK and YN were employed by Organization/Management Headquarters, Iwate Co-op. MY was employed by The Ajinomoto Foundation. Co-author YK has received research funding from TAF. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ito, Konno, Nozaki, Fukushi, Kanno, Kawamura, Nakamura, Yamada, Kuroda, Kuchii, Kinoshita, Nabetani and Fukuda.)

Both cancer and cardiovascular disease (CVD) cause skeletal muscle mass loss, thereby increasing the likelihood of a poor prognosis. We investigated the association between cancer history and physical function and their combined association with prognosis in patients with CVD. We retrospectively reviewed 3,796 patients with CVD (median age: 70 years; interquartile range [IQR]: 61-77 years) who had undergone physical function tests (gait speed and 6-minute walk distance [6MWD]) at discharge. We performed multiple linear regression analyses to assess potential associations between cancer history and physical function. Moreover, Kaplan-Meier curves and Cox regression analyses were used to evaluate prognostic associations in four groups of patients categorized by the absence or presence of cancer history and of high or low physical function. Multiple regression analyses showed that cancer history was significantly and independently associated with a lower gait speed and 6MWD performance. A total of 610 deaths occurred during the follow-up period (median: 3.1 years; IQR: 1.4-5.4 years). The coexistence of low physical function and cancer history in patients with CVD was associated with a significantly higher mortality risk, even after adjusting for covariates (cancer history/low gait speed, hazard ratio [HR]: 1.93, P < 0.001; and cancer history/low 6MWD, HR: 1.61, P = 0.002). Cancer history is associated with low physical function in patients with CVD, and the combination of both factors is associated with a poor prognosis., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Aims: The risk of developing heart failure (HF) after acute coronary syndrome (ACS) remains high. It is unclear whether skeletal muscle strength, in addition to existing risk factors, is a predictor for developing HF after ACS. We aimed to clarify the relationship between quadriceps isometric strength (QIS), a skeletal muscle strength indicator, and the risk of developing HF in patients with ACS., Methods and Results: We included 1053 patients with ACS without a prior HF or complications of HF during hospitalization. The median (interquartile range) age was 67 (57-74) years. The patients were classified into two groups-high and low QIS-using the sex-specific median QIS. The endpoint was HF admissions. During a mean follow-up period of 4.4 ± 3.7 years, 75 (7.1%) HF admissions were observed. After multivariate adjustment, a high QIS was associated with a lower risk of HF [hazard ratio: 0.52, 95% confidence interval (CI): 0.32-0.87]. Hazard ratio (95% CI) per 5% body weight increment increase of QIS for HF incidents was 0.87 (0.80-0.95). Even when competing risks of death were taken into account, the results did not change. The inclusion of QIS was associated with increases in net reclassification improvement (0.26; 95% CI: 0.002-0.52) and an integrated discrimination index (0.01; 95% CI: 0.004-0.02) for HF., Conclusion: The present study showed that a higher level of QIS was strongly associated with a lower risk of developing HF after ACS. These findings suggest that skeletal muscle strength could be one of the factors contributing to the risk of developing HF after ACS., Competing Interests: Conflict of interest: K.K. received funding outside of the submitted work from Eiken Chemical Co. Ltd and SoftBank Corporation. M.Y. has no conflict of interest related to the conduct of this study, but he holds company stock (<5% of the total) and receives a salary as one of the directors of an employer. All other authors have nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The Shiga Epidemiological Study of Subclinical Atherosclerosis was conducted in Kusatsu City, Shiga, Japan, from 2006 to 2008. Participants were measured for LDL-p through nuclear magnetic resonance technology. 740 men participated in follow-up and underwent 1.5 T brain magnetic resonance angiography from 2012 to 2015. Participants were categorized as no-ICAS, and ICAS consisted of mild-ICAS (1 to < 50%) and severe-ICAS (≥ 50%) in any of the arteries examined. After exclusion criteria, 711 men left for analysis, we used multiple logistic regression to examine the association between lipid profiles and ICAS prevalence. Among the study participants, 205 individuals (28.8%) had ICAS, while 144 individuals (20.3%) demonstrated discordance between LDL-c and LDL-p levels. The discordance "low LDL-c-high LDL-p" group had the highest ICAS risk with an adjusted OR (95% CI) of 2.78 (1.55-5.00) in the reference of the concordance "low LDL-c-low LDL-p" group. This was followed by the concordance "high LDL-c-high LDL-p" group of 2.56 (1.69-3.85) and the discordance "high LDL-c-low LDL-p" group of 2.40 (1.29-4.46). These findings suggest that evaluating LDL-p levels alongside LDL-c may aid in identifying adults at a higher risk for ICAS., (© 2024. The Author(s).)

Background: This study aimed to evaluate the effects of orthogeriatric co-management of hip fractures at a regional core hospital., Methods: This study included patients with proximal hip fracture. Patients were divided into two groups, conventional multidisciplinary group I including patients attending the hospital between April 2015 and March 2016 and orthogeriatric group II including patients attending the hospital between April 2016 and March 2017, which were compared retrospectively. In the control group, the conventional multidisciplinary team treated patients as whole-body controls. In the intervention group, the newly recruited geriatricians performed physical examinations, laboratory tests, radioactive imaging, and physiological tests. Furthermore, they consulted ward pharmacists, rigorously conducted positive polypharmacy interventions , and evaluated the type and number of mediated drugs on admission., Results: The number of medicated drugs significantly decreased from 6.03 ± 4.3 on admission to 5.50 ± 3.59 on discharge in group II, whereas group I did not show a significant decrease. Despite the more number of hospitalized patients in group II (166 patients) than in group I (126 patients), the recovery rate from postoperative urinary retention increased significantly from 57.8% (19/30) in group I to 84.3% (32/59) in group II (p = 0.049), while the incidence of aspiration pneumonia decreased from 7.1% (9/126) in group I to 2.49% (4/166) in group II (p = 0.08). The patients received six or more prescribed drugs on admission, and the number remained constant. However, the number of medicated drugs on discharge showed a marginally significant decrease from 6.03 ± 4.3 in group I to 5.50 ± 3.59 in group II (p < 0.05)., Conclusions: Compared to the conventional multidisciplinary group, the orthogeriatric team contributed to reducing the number of multi-effect drugs and perioperative complications without negatively affecting mortality despite the increased number of patients. The in-hospital mortality rate did not change between the groups. The orthogeriatric program succeeded in preventing and treating perioperative complications., Competing Interests: Declaration of competing interest None., (Copyright © 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Aim: To investigate the incidence and in-hospital mortality of acute myocardial infarction (AMI) by conforming to the Universal Definition of Myocardial Infarction (UDMI) in a population-based registry., Methods: The Shiga Stroke and Heart Attack Registry is a multicenter, population-based registry in the Shiga Prefecture, designed to evaluate the incidence and prognosis of acute cerebro-cardiovascular diseases. We registered patients with AMI as defined by the UDMI, who developed AMI from January 2014 to December 2015 in the Shiga Prefecture. The incidence rate of AMI was calculated and standardized for age by a direct method using the 2015 Japanese population. We also evaluated the in-hospital mortality among hospitalized patients with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI)., Results: A total of 1,587 patients were diagnosed with AMI, and the age-adjusted incidence rate was 61.9 per 100,000 person-years. The proportions of patients with STEMI, NSTEMI, and type 3 myocardial infarction were 57%, 30%, and 12%, respectively. The incidence rates of AMI increased with age regardless of sex, which was the highest in those 85 years and older, with 389.7 per 100,000 person-years in men and 221.8 per 100,000 person-years in women. Age-adjusted in-hospital mortality among hospitalized patients with STEMI and NSTEMI was 12.3% and 5.8%, respectively., Conclusions: This population-based registry clarified the age-adjusted incidence rate of AMI under the application of the UDMI, highlighting that in-hospital mortality is still high among patients with STEMI in Japan.

Background: Acute aortic dissection (AAD) is a life-threatening cardiovascular disease, with a reported incidence rate ranging from 2.5 to 7.2 per 100,000 person-years in several population-based registries in Western countries, but epidemiological data are lacking in Japan., Methods and results: The Shiga Stroke and Heart Attack Registry is an ongoing multicenter population-based registry of cerebro-cardiovascular diseases. We enrolled patients who developed AAD, defined by any imaging examination method from 2014 to 2015 in Shiga Prefecture. Death certificates were used to identify cases that were not registered at acute care hospitals. The incidence rates of AAD were calculated by age categories and adjusted using standard populations for comparison. We evaluated differences in patient characteristics between Stanford type A-AAD and type B-AAD subtypes. A total of 402 incident cases with AAD were analyzed. The age-adjusted incidence rates using the 2015 Japanese population and the 2013 European Standard Population were 15.8 and 12.2 per 100,000 person-years, respectively. Compared with cases of type B-AAD, those with type A-AAD were older (75.0 vs. 69.9 years, P=0.001) and more likely to be women (62.3% vs. 28.6%, P<0.001)., Conclusions: Population-based incidence rates of AAD in Japan appear to be higher than in previous reports from Western countries. Incident cases with type A-AAD were older and female predominance.

Objectives: To examine the national, 6-year trends in in-hospital clinical outcomes of patients with subarachnoid haemorrhage (SAH) who underwent clipping or coiling and the prognostic influence of temporal trends in the Comprehensive Stroke Center (CSC) capabilities on patient outcomes in Japan., Design: Retrospective study., Setting: Six hundred and thirty-one primary care institutions in Japan., Participants: Forty-five thousand and eleven patients with SAH who were urgently hospitalised, identified using the J-ASPECT Diagnosis Procedure Combination database., Primary and Secondary Outcome Measures: Annual number of patients with SAH who remained untreated, or who received clipping or coiling, in-hospital mortality and poor functional outcomes (modified Rankin Scale: 3-6) at discharge. Each CSC was assessed using a validated scoring system (CSC score: 1-25 points)., Results: In the overall cohort, in-hospital mortality decreased (year for trend, OR (95% CI): 0.97 (0.96 to 0.99)), while the proportion of poor functional outcomes remained unchanged (1.00 (0.98 to 1.02)). The proportion of patients who underwent clipping gradually decreased from 46.6% to 38.5%, while that of those who received coiling and those left untreated gradually increased from 16.9% to 22.6% and 35.4% to 38%, respectively. In-hospital mortality of coiled (0.94 (0.89 to 0.98)) and untreated (0.93 (0.90 to 0.96)) patients decreased, whereas that of clipped patients remained stable. CSC score improvement was associated with increased use of coiling (per 1-point increase, 1.14 (1.08 to 1.20)) but not with short-term patient outcomes regardless of treatment modality., Conclusions: The 6-year trends indicated lower in-hospital mortality for patients with SAH (attributable to better outcomes), increased use of coiling and multidisciplinary care for untreated patients. Further increasing CSC capabilities may improve overall outcomes, mainly by increasing the use of coiling. Additional studies are necessary to determine the effect of confounders such as aneurysm complexity on outcomes of clipped patients in the modern endovascular era., Competing Interests: Competing interests: KI reports grant support from Idorsia Pharmaceuticals Japan Limited. The other authors report no conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We assessed risk factors for postoperative urinary retention (UR) in elderly males with femoral bone fractures: 169 Japanese males (mean age 81.95 ± 1.19 years) who had undergone hip surgery at a municipal hospital (Toyama, Japan). A multiple logistic regression analysis was used to test possible risk factors for UR: age, body mass index, serum albumin, cognitive impairment, activities of daily living (ADL), and history of diabetes mellitus (DM). UR occurred in 24 (14.2%) of the 169 patients. A multivariate logistic regression analysis with age adjustment showed that ADL (odds ratio [OR] 3.88; 95% confidence interval [CI]: 1.2-12.5, p=0.023) was significantly associated with the development of UR, and a history of DM showed marginal significance for UR occurrence (OR 0.36, 95%CI: 0.11-10, p=0.064). These results suggests that ADL is a risk factor for UR development in elderly males who have undergone surgery for femoral neck or trochanter fractures., Competing Interests: No potential conflict of interest relevant to this article was reported.

Aim: The relationship of blood pressure (BP) indexes (systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse pressure [PP], mean arterial pressure [MAP]) to subclinical cerebrovascular diseases (SCVDs) remains unclear. This study aimed to elucidate the relationship of four BP indexes measured at two visits on SCVDs assessed by magnetic resonance imaging (MRI) in general Japanese men., Methods: In general Japanese men aged 40-79 years (N=616), office BP indexes were measured at two visits (Visits 1 [2006-2008] and 2 [2010-2014]). MRI images obtained on the third visit (2012-2015) were examined for prevalent SCVDs: lacunar infarction, periventricular hyperintensity (PVH), deep subcortical white matter hyperintensity (DSWMH), microbleeds, and intracranial artery stenosis (ICAS). Using a multivariable logistic regression analysis, we computed and estimated the odds ratio of each prevalent SCVD for one standard deviation higher BP indexes. The same analyses were performed using home BP., Results: All four office BP indexes at both visits associated with lacunar infarction. Visit 1 and 2 DBP and Visit 1 MAP associated with PVH and DSWMH, and Visit 1 SBP associated with DSWMH. All Visit 2 BP indexes appear to show stronger association with microbleeds than Visit 1 indexes, and Visit 1 and 2 SBP, PP, and MAP showed similar associations with ICAS. Additional analyses using home BP indexes revealed similar relationships; however, the significance of some relationships decreased., Conclusion: In general Japanese men, BP indexes were associated with most of SCVDs, and BP indexes measured at different periods associated with different SCVDs assessed by MRI.

Introduction: The purpose of this study was to investigate seasonal variation in stroke incidence using data from a large-scale stroke registry of general population in current Japan., Methods: Shiga Stroke Registry (SSR) is an ongoing population-based registry of stroke that occurred in the Shiga Prefecture in central Honshu, Japan. A total 6,688 cases of first-ever stroke, with onset dates ranging from 1 January 2011 to 31 December in 2013 were included in this study. Incidence rates of first-ever stroke in each season were estimated using the person-year approach and adjusted for age and sex using the Poisson regression models., Results: From 2011 to 2013, we identified a total of 6,688 stroke cases (3,570 men, 3,118 women), of which 4,480 cases had ischemic stroke (2,518 men, 1,962 women), 1,588 had intracerebral hemorrhage (857 men, 731 women) and 563 had subarachnoid hemorrhage (166 men, 397 women). Age- and sex-adjusted incidence rates of total stroke were 151 (95% confidence interval [CI] 144-160, p = <0.001 vs. summer) in spring, 130 (95% CI 122-137) in summer, 141 (95% CI 133-149, p = 0.020 vs. summer) in autumn and 170 (95% CI 161-179, p = <0.001 vs. summer) in winter. Seasonal variation was more pronounced in intracerebral hemorrhage than in ischemic stroke., Conclusion: In the present large-scale stroke registry of general population, incidence rates of stroke were highest in winter and lowest in summer in current Japan., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Each year, the Japan Neurosurgical Society (JNS) reports up-to-date statistics from the Japan Neurosurgical Database regarding case volume, patient demographics, and in-hospital outcomes of the overall cohort and neurosurgical subgroup according to the major classifications of main diagnosis. We hereby report patient demographics, in-hospital mortality, length of hospital stay, purpose of admission, number of medical management, direct surgery, endovascular treatment, and radiosurgery of the patients based on the major classifications and/or main diagnosis registered in 2018 and 2019 in the overall cohort (523283 and 571143 patients, respectively) and neurosurgical subgroup (177184 and 191595 patients, respectively). The patient demographics, disease severity, proportion of purpose of admission (e.g., operation, 33.9-33.5%) and emergent admission (68.4-67.8%), and in-hospital mortality (e.g., cerebrovascular diseases, 6.3-6.5%; brain tumor, 3.1-3%; and neurotrauma, 4.3%) in the overall cohort were comparable between 2018 and 2019. In total, 207783 and 225217 neurosurgical procedures were performed in the neurosurgical subgroup in 2018 and 2019, respectively, of which endovascular treatment comprised 19.1% and 20.3%, respectively. Neurosurgical management of chronic subdural hematoma (19.4-18.9%) and cerebral aneurysm (15.4-14.8%) was most common. Notably, the proportion of management of ischemic stroke/transient ischemic attack, including recombinant tissue plasminogen activator infusion and endovascular acute reperfusion therapy, increased from 7.5% in 2018 to 8.8% in 2019. The JNS statistical update represents a critical resource for the lay public, policy makers, media professionals, neurosurgeons, healthcare administrators, researchers, health advocates, and others seeking the best available data on neurosurgical practice.

Background: This study was performed to test the hypothesis that low quadriceps isometric strength (QIS) is associated with greater risk of mortality and has the additive prognostic significance to the severity of heart failure (HF) and gait speed in older patients with HF., Methods: A retrospective cohort study was performed in 1273 patients ≥ 60 years of age with HF (mean age 75 ± 8 years, 59.1% men); all of whom were evaluated during hospitalization for usual gait speed and maximal QIS. The QIS was expressed relative to body mass (% BM). The endpoint was all-cause mortality., Results: Over a median follow-up period of 1.59 years (interquartile range, 0.58 to 3.42 years), 224 patients died. The cutoff value based on the Youden index for the QIS discriminating those at high risk of mortality was 36.2% BM for overall, and we defined less than this cutoff point of QIS as low QIS. After adjustment for the HF risk score, the hazard ratio in low QIS was 1.55 for overall (95% confidence interval [CI], 1.17-2.06). The addition of low QIS to the HF risk score and gait speed was associated with significant increases in both net reclassification improvement (NRI, 0.239 for overall; 95% CI, 0.096-0.381) and integrated discrimination improvement (IDI, 0.004 for overall; 95% CI, 0.001-0.009) for all-cause mortality., Conclusion: Low QIS was strongly associated with poor prognosis and showed complementary prognostic predictive capability to the HF risk score and gait speed in older patients with HF., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Cerebral small vessel disease (CSVD) is a common subclinical feature of the aging brain. Steps per day may contribute to its prevention. We herein investigated the association between step counts and CSVD in a healthy Japanese male population., Methods: We analyzed data from 680 men who were free of stroke and participated in this observational study. Seven-day step counts were assessed at baseline (2006-2008) using a pedometer. CSVD was assessed at follow-ups (2012-2015) based on deep and subcortical white matter hyperintensities (WMHs), periventricular hyperintensities, lacunar infarcts, and cerebral microbleeds on magnetic resonance imaging. Using a logistic regression analysis, we computed the adjusted odds ratios, with 95% CIs, of prevalent CSVD according to quartiles of step counts (reference: Q1). We also investigated the association between step counts and WMH volumes using a quantile regression., Results: Steps per day were significantly associated with lower odds ratios, with the lowest at Q3 (8175-10 614 steps/day), of higher (versus low or no burden) deep and subcortical WMHs (odds ratio, 0.52 [95% CI, 0.30-0.89]), periventricular hyperintensities (0.50 [95% CI, 0.29-0.86]), and lacunar infarcts (0.52 [95% CI, 0.30-0.91]) compared with Q1 (≤6060 steps/day) but not cerebral microbleeds. An inverse linear association was observed between step counts and WMH volumes. These associations were independent of age and smoking and drinking status and remained consistent when adjusted for vascular risk factors., Conclusions: We found a J-shaped relationship between step counts and prevalent CSVD in healthy Japanese men, with the lowest risk being observed among participants with ≈8000 to 10 000 steps/day. Higher steps were also associated with lower WMH volumes.

Background: The international Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the EfficaCy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate versus Acetylsalicylic Acid in Patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS) trial did not demonstrate superiority of dabigatran over aspirin for reduction of recurrent strokes in patients with embolic strokes of undetermined source (ESUS). Based on pre-defined subanalyses, the safety and efficacy of dabigatran vs. aspirin in Japanese patients was assessed., Methods and results: ESUS patients were randomized to receive either dabigatran (150 or 110 mg twice daily) or aspirin (100 mg once daily). Of 5,390 patients randomized, 594 were Japanese. Most Japanese patients (99.8%) underwent brain magnetic resonance imaging for trial screening, compared to 76.8% of non-Japanese (P<0.0001). In the Japanese cohort, over a 19.4-month median follow-up period, recurrent stroke as the primary outcome occurred in 20/294 patients (4.3%/year) in the dabigatran group and 38/300 (8.3%/year) in the aspirin group (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.32-0.94). Major bleeding occurred in 12 patients (2.5%/year) and 17 patients (3.5%/year), respectively (HR, 0.72; 95% CI, 0.34-1.52). In contrast, in the non-Japanese cohort, recurrent stroke occurred in 4.1%/year and 4.3%/year, respectively, showing no apparent difference in recurrent stroke for dabigatran vs. aspirin (HR, 0.91; 95% CI, 0.74-1.14). The P-interaction for treatment and region did not reach statistical significance (P=0.09)., Conclusions: Dabigatran was putatively associated with a lower relative risk of recurrent stroke compared with aspirin in Japanese ESUS patients.

Aim: Coronary artery calcification (CAC) is an independent predictor of stroke and dementia, in which subclinical cerebrovascular diseases (SCVDs) play a vital pathogenetic role. However, few studies have described the association between CAC and SCVDs. Therefore, the aim of this study was to assess the clinical relationship between CAC and SCVDs in a healthy Japanese male population., Methods: In this observational study, 709 men, free of stroke, were sampled from a city in Japan from 2010 to 2014. CAC was scored using the Agatston method. The following SCVDs were assessed using magnetic resonance imaging: intracranial arterial stenosis (ICAS), lacunar infarction, deep and subcortical white matter hyperintensity (DSWMH), periventricular hyperintensity (PVH), and microbleeds. The participants were categorized according to CAC scores as follows: no CAC (0), mild CAC (1-100), and moderate-to-severe CAC (＞100). The adjusted odds ratios of prevalent SCVDs were computed in reference to the no-CAC group using logistic regression., Results: The mean (standard deviation) age of the participants was 68 (8.4) years. Participants in the moderate-to-severe CAC category showed significantly higher odds of prevalent lacunar infarction, DSWMH, and ICAS in age-adjusted and risk-factor-adjusted models. Microbleeds and PVH, in contrast, did not show any significant associations. The trends for CAC with lacunar infarction, DSWMH, and ICAS were also significant (all P-values for trend ≤ 0.02)., Conclusions: Higher CAC scores were associated with higher odds of lacunar infarction, DSWMH, and ICAS. The presence and degree of CAC may be a useful indicator for SCVDs involving small and large vessels.

Compared to the general population, elderly patients with cardiovascular disease have a higher prevalence of sarcopenia, and it shows an association with increased mortality risk. Although several studies have indicated that atherosclerosis may cause sarcopenia in community dwelling elderly subjects, the association between sarcopenia and atherosclerosis is not clear in patients with ischemic heart disease (IHD). The present study was performed to examine the association between muscle function and atherosclerosis in elderly patients with IHD. We reviewed the findings of 321 consecutive patients ≥ 65 years old with IHD. Three measures of muscle function were examined, i.e., gait speed, quadriceps isometric strength, and handgrip strength, just before hospital discharge. In addition, we measured intima-media thickness (IMT) as a parameter of arteriosclerosis. To investigate the association between sarcopenia and atherosclerosis, patients were divided into Group H (high), Group M (middle), and Group L (low) according to the tertiles of muscle function, and IMT was compared between the three groups. In addition, we considered the association between IMT thickening and muscle function. The mean age of the study population was 74.1 ± 6.0 years and 73.2% of the patients were men. IMT was compared between groups stratified according to gait speed and quadriceps isometric strength, and the results indicated that IMT was significantly lower in Group H than in Groups L and M (p < 0.05). In addition, gait speed and quadriceps isometric strength were associated with IMT thickening (p < 0.05). Parameters reflecting muscle function of the lower limbs are associated with atherosclerosis in patients with IHD.

The simplified frailty scale is a simple frailty assessment tool modified from Fried's phenotypic frailty criteria, which is easy to administer in hospitalized patients. The applicability of the simplified frailty scale to indicate prognosis in elderly hospitalized patients with cardiovascular disease (CVD) was examined.This cohort study was performed in 895 admitted patients ≥ 65 years (interquartile range, 71.0-81.0, 541 men) with CVD. Patients were classified as robust, prefrail, or frail based on the five components of the simplified frailty scale: weakness, slowness, exhaustion, low activity, and weight loss. The primary endpoint was the composite outcome of all-cause mortality and unplanned readmission for CVD.Patients positive for greater numbers of frailty components showed higher risk of all-cause mortality or unplanned CVD-related readmission (P for trend < 0.001). Classification as both frail (adjusted HR: 3.27, 95% confidence interval [CI]: 1.49-7.21, P = 0.003) and prefrail (adjusted HR: 2.19, 95% CI: 1.00-4.79, P = 0.049) independently predicted the composite endpoint compared with robust after adjusting for potential confounding factors. The inclusion of prefrail, frail, and number of components of frailty increased both continuous net reclassification improvement (0.113, P = 0.049; 0.426, P < 0.001; and 0.321, P < 0.001) and integrated discrimination improvement (0.007, P = 0.037; 0.009, P = 0.038; and 0.018, P = 0.002) for the composite endpoint.Higher scores on the simplified frailty scale were associated with increased risk of mortality or readmission in elderly patients hospitalized for CVD.

Background: Despite many effective strategies for the prevention of recurrent stroke, individuals who survive an initial stroke have been shown to be at high risk of recurrent stroke. The aim of this study was to investigate the current status of stroke recurrence after first-ever stroke using a population-based stroke registry in Japan., Methods and results: As part of the Shiga Stroke and Heart Attack Registry, the Shiga Stroke Registry is an ongoing population-based stroke registry study that covers approximately 1.4 million residents of Shiga Prefecture, Japan. A total of 1,883 first-ever stroke survivors at 28 days was registered in 2011 and followed-up until the end of 2013. Recurrence was defined as any type of stroke after 28 days from the onset of an index event. Two-year cumulative recurrence rates were estimated using cumulative incidence function methods. Over a mean 2.1-year follow-up period, 120 patients experienced recurrent stroke and 389 patients died without recurrence. The 2-year cumulative recurrence rate was higher in patients with index ischemic stroke (6.8%) than in those with index hemorrhagic stroke (3.8%)., Conclusions: Two-year cumulative recurrence rate after first-ever stroke remained high, particularly among patients with ischemic stroke, in the present population-based registry study in a real-world setting in Japan. Further intensive secondary prevention strategies are required for these high-risk individuals.

The Japan Neurosurgical Database (JND) is a prospective observational study registry established in 2017 by the Japan Neurosurgical Society (JNS) to visualize real-world clinical practice, promote science, and improve the quality of care and neurosurgery board certification in Japan. We summarize JND's aims and methods, and describes the 2018 survey results. The JND registered in-hospital patients' clinical data mainly from JNS training institutions in 2018. Caseload, patient demographics, and in-hospital outcomes of the overall cohort and a neurosurgical subgroup were examined according to major classifications of main diagnosis. Neurosurgical caseload per neurosurgeon in training in core hospitals in 2018 was calculated as an indicator of neurosurgical training. Of 523,283 cases (male 55.3%) registered from 1360 participating institutions, the neurosurgical subgroup comprised of 33.9%. Among the major classifications, cerebrovascular diseases comprised the largest proportion overall and in the neurosurgical subgroup (53.1%, 41.0%, respectively), followed by neurotrauma (19.1%, 25.5%), and brain tumor (10.4%, 12.8%). Functional neurosurgery (6.4%, 3.7%), spinal and peripheral nerve disorders (5.1%, 10.1%), hydrocephalus/developmental anomalies (2.9%, 5.3%), and encephalitis/infection/inflammatory and miscellaneous diseases (2.9%, 1.6%) comprised smaller proportions. Most patients were aged 70-79 years in the overall cohort and neurosurgical subgroup (27.8%, 29.4%). Neurotrauma and cerebrovascular diseases in the neurosurgical subgroup comprised a higher and lower proportion, respectively, than in the overall cohort in elderly patients (e.g. 80 years, 46.9% vs. 33.5%, 26.8% vs. 54.4%). The 2018 median neurosurgical caseload per neurosurgeon in training was 80.7 (25-75th percentile 51.5-117.5). These initial results from 2018 reveal unique aspects of neurosurgical practice in Japan.

Objective: Japan has been reported to have the highest (and increasing) incidence of subarachnoid hemorrhage (SAH) in the world. However, there has never been a report on the nationwide incidence rate and recent trends for SAH in Japan. In this register-based study, the authors aimed to clarify the estimated nationwide SAH incidence rate and the recent trend in SAH incidence in Japan and the reasons for any changes in this trend., Methods: The authors compiled data from the Japanese Ministry of Health, Labour and Welfare and from the records of the Japan Neurosurgical Society. They reviewed the age-standardized nationwide SAH mortality rate, the estimated age-standardized SAH incidence rate according to the age-standardized SAH mortality rate, and the estimated crude SAH incidence rate, including the 95% confidence intervals, from 2003 to 2015. The trends in the number of treatments for unruptured and ruptured cerebral aneurysms, as well as the prevalence of hypertension, current smoking status, and use of cholesterol-lowering drugs, were assessed. The estimated treatment rate for unruptured cerebral aneurysms (UCAs) was also calculated along with the 95% confidence interval., Results: The estimated age-standardized nationwide SAH incidence rate significantly declined from 31.34 cases (95% CI 31.32-31.34) to 27.63 (95% CI 27.59-27.63; decrease by 11.8%) per 100,000 person-years. This decline was based on the 2010 population as the reference from 2003 through 2015 and a case-fatality rate of SAH that was assumed to decrease by 1% annually from 44% in 2003 to 32% in 2015. According to sensitivity analysis, the change rate of the estimated age-standardized SAH incidence rate ranged from -56.69% to 23.27%, with a mean of -30.91% (SD 20.52%), and there were decline trends in 92% of all trends. The estimated nationwide crude SAH incidence rate also showed a significant decline from 23.79 (95% CI 23.78-23.79) to 20.25 (95% CI 20.24-20.25; decrease by 14.9%) per 100,000 person-years. The trend in treatment numbers for UCAs increased significantly (p < 0.0001) from 2003 through 2015; however, the estimated treatment rate for UCAs was only 0.19 (95% CI 0.19-0.20) to 0.51 (95% CI 0.50-0.51) among all UCA patients. The prevalence of hypertension (males, p = 0.0003; females, p < 0.0001) and current smoking status (males, p < 0.0001; females, p = 0.0002) declined significantly from 2003 through 2015, while the use of cholesterol-lowering drugs increased significantly (males, p < 0.0001; females, p = 0.0005) during the same period., Conclusions: The estimated nationwide SAH incidence rate in Japan was higher than rates in other countries, although it has declined recently. An improving lifestyle may have contributed to the declining rate of SAH incidence in Japan.

Although the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC) is useful to assess decline of instrumental activities of daily living (IADL) in Japanese individuals, limited data are available in patients with heart failure (HF). This study was performed to investigate the prognostic value of IADL evaluated by TMIG-IC in initial HF hospitalization patients aged ≥ 65 years. We reviewed 297 elderly HF patients with independent basic ADL before hospitalization. Patients with prior HF were excluded. Five TMIG-IC items were investigated as IADL parameters. Patients with full IADL scores were defined as "independent" and others were defined as "dependent". The endpoint was all-cause mortality, and multivariable analysis was performed to identify IADL risk. The median age was 76 years, and 55% of the patients were male. Forty-one deaths occurred over a median follow-up period of 1.01 years. After adjusting for existing risk factors, including Seattle Heart Failure Score, dependent patients had higher mortality risk than independent patients [hazard ratio 3.64, 95% confidence interval (CI) 1.57-8.43], and mortality risk decreased by 16% for each 1-point increase in IADL score (hazard ratio 0.84, 95% CI 0.71-0.99). In conclusion, limited IADL indicated by TMIG-IC was associated with poorer long-term mortality rate in elderly patients with HF. This inexpensive and easily applicable tool will support decision making in cardiac rehabilitation.

Purpose: The purpose of this study was to determine whether gait speed affects the obesity paradox in older patients with cardiovascular disease., Methods: The study population consisted of 2224 patients ≥60 years old with cardiovascular disease admitted to hospital between May 1, 2006, and January 31, 2018. Body mass index (BMI) and gait speed before hospital discharge were determined, and patients were divided into two groups: slow and preserved gait speed (≤0.8 and >0.8 m/s, respectively), according to the algorithm for sarcopenia diagnosis. The slow and preserved gait speed groups were also further subdivided according to BMI: <18.5 kg/m 2 , 18.5-24.9 kg/m 2 , and BMI ≥25.0 kg/m 2 . The study endpoint was all-cause mortality., Results: The study population (male: 66.7%) had a mean age of 73.1 ± 7.6 years. Over a median follow-up period of 1.69 years (interquartile range 0.67-3.67 years), 283 patients died. Higher BMI was associated with favorable prognosis in the group with preserved gait speed but not in the group with slow gait speed after adjusting for other prognostic factors. Adding BMI to the clinical model significantly increased the area under the receiver operating characteristic curve in the group with preserved gait speed (0.744 vs 0.726, P = 0.028) but not in the group with slow gait speed (0.716 vs 0.716, P = 0.789)., Conclusions: Higher BMI was consistently associated with favorable prognosis in patients with cardiovascular disease and preserved gait speed but not in those with slow gait speed. These findings indicated that physical frailty influences the obesity paradox in older patients with cardiovascular disease., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The characteristics of cerebral aneurysms in Japan differ from other countries in the higher incidence of unruptured cerebral aneurysm detected by brain check-up screening, higher rupture rate of unruptured cerebral aneurysm, higher incidence of subarachnoid hemorrhage, and superior outcome after subarachnoid hemorrhage based on meta-analysis. Head shape, genetic features, environmental factors, demographics, and medical system in Japan are also different from other countries. Unruptured cerebral aneurysms are 2.8 times more likely to rupture in Japanese than western aneurysms, resulting in the highest incidence of subarachnoid hemorrhage in the world. The exact and specific mechanisms of de novo, growth, and rupture of cerebral aneurysms have not been elucidated. Investigations will contribute to the understanding of cerebral aneurysms and subarachnoid hemorrhage worldwide. Some features of cerebral aneurysm in Japan are discussed for possible research guidance in the elucidation of the predominance of subarachnoid hemorrhage in Japan.

Background and Purpose- Few community-based studies have reported the prevalence of intracranial artery stenosis (ICAS) assessed with magnetic resonance angiography. The aim was to determine the prevalence of ICAS using magnetic resonance angiography in a general population of Japanese men and to investigate the associations between ICAS and conventional cardiovascular risk factors. Methods- The Shiga Epidemiological Study of Subclinical Atherosclerosis randomly recruited and examined participants from Kusatsu City, Shiga, Japan, in 2006 to 2008 (baseline); 740 men returned for follow-up and underwent 1.5 T brain magnetic resonance angiography in 2012 to 2015. Participants were categorized as having no-ICAS, mild-ICAS (1 to <50%), or severe-ICAS (≥50%) in any of the arteries examined. After excluding the men with a history of stroke, 709 men were analyzed using multivariable logistic regression to assess independent associations of conventional cardiovascular risk factors with reference to the no-ICAS group. Results- The participants' mean age was 68.0 years. The age-standardized prevalences of mild and severe-ICAS were 20.7% and 4.5%, respectively (with the population of the 2010 Japanese vital statistics as the reference). Age, hypertension, diabetes mellitus, and dyslipidemia were associated with a higher prevalence of severe-ICAS after simultaneous adjustment for conventional cardiovascular risk factors. Conclusions- In a community-based sample of Japanese men, ICAS was estimated to be present in 25.2%, and related to metabolic risk factors, in addition to hypertension and age. These results support the importance of comprehensive management of conventional cardiovascular risk factors for stroke prevention.

Background: Home-visiting nurses are expected to enhance their ability to provide adequate nursing care in a relatively isolated work environment. However, the isolated work environment leads to less opportunity to share patient information. We investigated factors relevant to better patient information sharing among home-visiting nurses, which would contribute to the improved care performance of these nurses., Methods: A cross-sectional study with anonymous self-administered questionnaire was conducted between June 2015 and September 2015 in two districts of Japan. Home-visiting nurses who were working at home health care agencies were recruited. The questionnaires consisted of items on demographic data, job-related variables, communication in the workplace, the current state of patient information sharing, opportunities (or measures) of patient information sharing in the workplace, and job satisfaction. Descriptive analyses were performed on all variables, using the Chi-square test, Fisher's exact test, or Mann-Whitney U-test. Logistic regression analyses were conducted to identify the factors associated with better information sharing, adjusting the years of home-visiting nursing experience as the control variable., Results: Of 762 anonymous self-administered questionnaires were mailed, data from 482 participants who consented to this study and had no missing answer were analyzed. Of the total, 77.2% shared the patients' information. Having a friendly adviser (OR = 2.51, 95% CI = 1.14-5.55, p = 0.023), attending some conferences (OR = 2.32, 95% CI = 1.12-4.82, p = 0.024), joining workshops (OR = 1.89, 95% CI = 1.15-3.10, p = 0.012), and years of home-visiting nursing experience (OR = 1.27, 95% CI = 1.03-1.57, p = 0.025) were significantly associated with sufficient sharing of the information. Nurses sufficiently sharing the information were well satisfied with their job (OR = 5.38, 95% CI =3.19-9.09, p < 0.001) and highly preferred a career in home-visiting nursing care (OR = 5.62, 95% CI =3.41-9.27, p < 0.001)., Conclusions: The results suggested that having opportunities to discuss face-to-face such as at conferences and workshops as well as promoting good relationships among colleagues in the workplace will contribute to better information sharing among home-visiting nurses. Home-visiting nurses with less years of experience need to be supported in order to share the information sufficiently. Additionally, sufficient information sharing was also associated with job satisfaction and preference for home-visiting nursing care, which might lead to job retention for home-visiting nurses.

Background: The detection of impaired physical performance in older adults with cardiovascular disease is essential for clinical management and therapeutic decision-making. There is a requirement for an assessment tool that can be used conveniently, rapidly, and securely in clinical practice for screening decreased physical performance., Objective: The present study was performed to evaluate the association of office-based physical assessments with decreased physical performance and to compare the prognostic capability of these assessments in older adults with cardiovascular disease., Methods: A total of 1,040 patients aged 75 years and older with cardiovascular disease were included in this analysis. One-leg standing time (OLST) and handgrip strength were measured as office-based physical assessment tools, and short physical performance battery (SPPB), 6-min walk distance, and usual gait speed were also measured at hospital discharge as measurements of physical performance. All-cause mortality was assessed by death registry at the hospital. We examined the association of office-based measures with physical performance and all-cause mortality., Results: The areas under the curve of OLST for SPPB < 10, 6-min walk distance < 300 m, and usual gait speed < 1.0 m/s were 0.87 (95% CI 0.83-0.91), 0.83 (95% CI 0.80-0.86), and 0.81 (95% CI 0.78-0.85), respectively. The discrimination abilities of OLST for decreased physical performance were significantly higher than those of handgrip strength. After adjusting for the effects of patient characteristics, the hazard ratio for all-cause mortality in the < 3 s group for OLST was 1.68 (95% CI 1.06-2.67, p = 0.03). Handgrip strength, however, was not significantly associated with mortality risk in these participants., Conclusion: Short OLST, in particular < 3 s, is associated with decreased physical performance and elevated mortality risk in elderly patients with cardiovascular disease. OLST can be conveniently measured in the clinician's office as a screening tool for impaired physical performance., (© 2019 S. Karger AG, Basel.)

Background: The impact of frailty on long-term prognosis in patients with heart failure (HF) remains unclear, and there is no simple and objective assessment for it. This study was performed to examine the association between frailty score and clinical outcome in elderly patients hospitalized for HF., Methods and Results: A retrospective cohort study was performed with 603 elderly patients with HF (mean age 75 ± 6 years, 378 [62.7%] men). Frailty was measured by a composite of 4 markers combined into a frailty score (possible range 0-12): gait speed, handgrip strength, serum albumin, and activities of daily living status. The patient population was divided into 2 groups with frailty score <5 (non-frail) or ≥5 (frail). The end point was all-cause mortality. Over a mean follow-up period of 1.7 ± 0.5 years, 89 patients died. After adjustment for several preexisting factors associated with prognosis, the frailty score (hazard ratio [HR] 1.11; P = .014) and frailty (HR 1.75; P = .036) were independently associated with all-cause mortality. The inclusion of frailty score significantly increased both continuous net reclassification improvement (0.341; P = .002) and integrated discrimination improvement (0.016; P = .039) for all-cause mortality., Conclusions: A simple and objective frailty score was associated with health outcome in elderly patients hospitalized for HF., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aim: We aimed to investigate the association between reduced lung function and cerebral small vessel diseases via cranial magnetic resonance imaging (MRI) in the cross-sectional study of the general Japanese population., Methods: We recruited participants aged ≥40 years from the general population of a single city in Japan. We clarified the comorbidities and treatments, smoking habits, second-hand smoke exposure, current alcohol consumption, education level, exercise habits, and occupation. The pulmonary function test was performed to assess the forced expiratory volume in 1 second (FEV 1 ) % predicted and forced vital capacity (FVC) % predicted values. Cranial MRI was performed to evaluate the white matter lesions (WMLs) and lacunar infarcts. We examined the association of the WMLs and lacunar infarcts with a 1-standard deviation (SD) lower in the FEV 1 % predicted and FVC % predicted, on the basis of the smoking status., Results: A total of 473 men were examined. The association of WMLs and lacunar infarcts with the spirometry-based indices were significant only in never smokers. The association between lung function impairment and cerebral small vessel disease did not change after further adjusting for second-hand smoke exposure., Conclusion: In a community-based sample of Japanese men, we found an association between reduced lung function and WMLs and lacunar infarcts in never smokers.

Background: Stroke is one of the leading causes of disability and mortality in Japan. The aim of the present analysis was to determine the non-acute survival rate after first-ever stroke using data from a large-scale population-based stroke registry in Japan., Methods and results: Shiga Stroke Registry is an ongoing population-based registry of stroke, which covers approximately 1.4 million residents of Shiga Prefecture in central Japan. A total of 2,176 first-ever stroke patients, who were registered in 2011, were followed up until December 2013. The 2-year cumulative survival rates were estimated using Kaplan-Meier method according to index stroke subtype. Cox proportional hazards models were used to assess predictors of all-cause death. During a 2-year follow-up period, 663 patients (30.5%) died. The 2-year cumulative survival rate after first-ever stroke was 69.5%. There was heterogeneity in 2-year cumulative survival according to stroke subtype: lacunar infarction, 87.2%; large artery infarction, 76.1%; cardioembolic infarction, 55.4%; intracerebral hemorrhage, 65.9%; and subarachnoid hemorrhage, 56.7%. Older age, male sex, medical history, higher Japan coma scale score on admission, and stroke subtype were associated with risk of all-cause death in ≤2 years., Conclusions: In the present population-based stroke registry with a real-world setting in Japan, 2-year cumulative mortality after first-ever stroke is still high (>30%), particularly for cardioembolic infarction, subarachnoid hemorrhage and intracerebral hemorrhage.

Background Although gait speed and six-minute walk distance are used to assess functional capacity in older patients with cardiovascular disease, their prognostic capabilities have not been directly compared. Methods The study population was identified from the Kitasato University Cardiac Rehabilitation Database and consisted of 1474 patients ≥60 years old with a mean age of 72.2 ± 7.1 years that underwent evaluation of both usual gait speed and six-minute walk distance in routine geriatric assessment between 1 June 2008-30 September 2015. Both gait speed and six-minute walk distance were determined on the same day at hospital discharge. Results Mean gait speed and six-minute walk distance in the whole population were 1.04 m/s and 381 m, respectively, and were strongly positively correlated ( r = 0.80, p < 0.001). A total of 180 deaths occurred during a follow-up of 2.3 ± 1.9 years. After adjusting for confounding factors, both gait speed (adjusted hazard ratio per 0.1 m/s increase: 0.87, 95% confidence interval: 0.81-0.93, p < 0.001) and six-minute walk distance (adjusted hazard ratio per 10-metre increase: 0.96, 95% confidence interval: 0.94-0.97, p < 0.001) were independent predictors of all-cause mortality. There was no significant difference in prognostic capability between gait speed and six-minute walk distance (c-index: 0.64 (95% confidence interval: 0.60-0.69) and 0.66 (95% confidence interval: 0.61-0.70), respectively, p = 0.357). Conclusions Gait speed and six-minute walk distance showed similar prognostic predictive ability for all-cause mortality in older cardiovascular disease patients, indicating the potential utility of gait speed as a simple risk stratification tool in older cardiovascular disease patients.

Objective: The purpose of this study is to assess the validity and feasibility of macrophage imaging using an ultrasmall superparamagnetic iron oxide nanoparticle, ferumoxytol, in the cerebral aneurysmal wall in an animal model and in humans., Materials and Methods: Engulfment of ferumoxytol by primary culture of macrophages and RAW264.7 cells was assessed. Uptake of ferumoxytol was evaluated histologically in a cerebral aneurysmal model in rats. In an exploratory clinical study of magnetic resonance macrophage imaging, 17 unruptured aneurysms in 17 patients were imaged using thin-slice gapless magnetic resonance images of 2D-gradient-recalled echo (2D-GRE) and 3D-T1-fast-spin echo sequences on day 0 and of the same sequences with infusion of ferumoxytol 24 hours after the first imaging. Pre- and postinfusion images were evaluated independently by 2 medical doctors., Results: Engulfment of ferumoxytol was confirmed in vitro, but the amount of ferumoxytol uptake was independent of the activation state or the differentiation state. Ferumoxytol uptake in CD68-positive cells was observed in the cerebral arterial walls of 4 out of 15 (26.7%) experimentally induced aneurysms in rats. In a clinical study, 17 aneurysms were enrolled and 2 aneurysms were not assessed because of incomplete images. Eleven aneurysms without oral intake of recent anti-inflammatory agents of the remaining 15 aneurysms showed ferumoxytol uptake on 2D-GRE subtraction images, and the size of the aneurysms was significantly related to positive images., Conclusions: Ferumoxytol uptake was confirmed in cultured macrophages and in the cerebral aneurysmal wall in rats. Thin-slice gapless magnetic resonance imaging with ferumoxytol in human cerebral aneurysmal walls may reflect macrophages in the cerebral aneurysmal wall, but its application to small-sized lesions may be restricted., (Copyright © 2017. Published by Elsevier Inc.)

Background: Surgical embolectomy is the most promising therapy for physically removing emboli from major cerebral arteries. However, it requires an experienced surgical team, time-consuming steps, and is not incorporated into acute stroke therapy., Methods: We established seamless collaboration between services, refined surgical techniques, and conducted a prospective trial of emergency surgical embolectomy. Surgical indications included the presence of acute hemispheric symptoms, absence of low-density area on computed tomography, evidence of internal carotid artery terminus or proximal middle cerebral artery occlusion, and availability of resources to start surgery within 3 hours of symptom onset. The indications were confirmed by an interdisciplinary team. We assessed revascularization rates, time from admission to surgery and from surgery to recanalization, procedural complications, and clinical outcomes., Results: Between 2005 and 2014, 14 consecutive patients with acute proximal middle cerebral artery or internal carotid artery terminus occlusion underwent emergency surgical embolectomy. All patients showed complete recanalization. Twelve patients survived and 7 had fair functional outcome (Rankin Scale score, ≤3). No significant procedural adverse events occurred. The mean times from admission to start of surgery, from surgery to recanalization, and from onset to recanalization were 14 minutes, 79 minutes, and 223 minutes, respectively., Conclusions: Our results suggest that microsurgical embolectomy can rapidly, safely, and effectively retrieve clots and deserves reappraisal, although the choice largely depends on local institutional expertise., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: We investigated the impact of reduced renal function on 24-h glucose variability in Japanese patients with type 2 diabetes mellitus (T2DM) treated with luseogliflozin., Methods: In this double-blind, placebo-controlled, crossover study, 37 Japanese patients with T2DM [glycated hemoglobin (HbA1c) 7.0-10.0%] and estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m(2) were randomized into two groups in which patients first received luseogliflozin then placebo, or vice versa, for 7 days each. Twenty-four-hour glucose variability was measured on day 7 in each period and was compared among patients divided into three groups according to their baseline eGFR (mL/min/1.73 m(2)): normal (≥90; n = 13; normal group), normal-to-mildly reduced renal function (≥75 to <90; n = 12; normal-mild group), and mild-to-moderately reduced renal function (<75; n = 9; mild-moderate group)., Results: The mean [95% confidence interval (CI)] placebo-subtracted 24-h cumulative urinary glucose excretion (g) was 82.1 (72.7, 91.5), 82.5 (73.4, 91.5), and 62.2 (51.2, 73.3); the placebo-subtracted 24-h mean glucose concentration (mg/dL) was -24.39 (-32.53, -16.26), -28.28 (-39.35, -17.22), and -11.53 (-23.93, 0.86); and the placebo-subtracted peak postprandial glucose (mg/dL) was -26.9 (-46.9, -6.9), -38.1 (-59.6, -16.6), and 1.5 (-25.5, 28.4) in the normal, normal-mild, and mild-moderate groups, respectively. The mean lowest glucose concentrations (placebo vs. luseogliflozin, mg/dL) decreased to similar levels in the normal (115.4 vs. 93.4), normal-mild (121.0 vs. 97.9), and mild-moderate (104.0 vs. 91.1) groups., Conclusion: This post hoc subanalysis revealed that although mild-to-moderately reduced renal function attenuated the glucose-lowering effects of luseogliflozin on peak postprandial glucose, it did not attenuate the effects of luseogliflozin on fasting glucose. These findings may explain the smaller increase in urinary glucose excretion in these patients relative to patients with normal renal function or normal-to-moderately reduced renal function. Further studies may be needed to examine these findings in large populations of patients with T2DM and reduced renal function., Trial Registration: JapicCTI-142548., Funding: Taisho Pharmaceutical Co., Ltd.

Objectives: The aim of this study was to identify risk factors for rupture of unruptured cerebral aneurysms (UCAs) in elderly Japanese patients aged 70 years or older., Methods: The participants included all patients 70 years of age or older in 3 prospective studies in Japan (the Unruptured Cerebral Aneurysm Study of Japan [UCAS Japan], UCAS II, and the prospective study at the Jikei University School of Medicine). A total of 1,896 patients aged 70 years or older with 2,227 UCAs were investigated. The median and mean follow-up periods were 990 and 802.7 days, respectively., Results: The mean aneurysm size was 6.2 ± 3.9 mm. Sixty-eight patients (3.6%) experienced subarachnoid hemorrhage during the follow-up period. Multivariable analysis per patient revealed that in patients aged 80 years or older (hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.16-3.49, p = 0.012), aneurysms 7 mm or larger (HR, 3.08; 95% CI, 1.35-7.03, p = 0.007 for 7-9 mm; HR, 7.82; 95% CI, 3.60-16.98, p < 0.001 for 10-24 mm; and HR, 43.31; 95% CI, 12.55-149.42, p < 0.001 for ≥25 mm) and internal carotid-posterior communicating artery aneurysms (HR, 2.45; 95% CI, 1.23-4.88, p = 0.011) were independent predictors for UCA rupture in elderly patients., Conclusions: In our pooled analysis of prospective cohorts in Japan, patient age and aneurysm size and location were significant risk factors for UCA rupture in elderly patients., (© 2015 American Academy of Neurology.)

Objective: To build a prediction model that estimates the 3-year rupture risk of unruptured saccular cerebral aneurysms., Methods: Survival analysis was done using each aneurysm as the unit for analysis. Derivation data were from the Unruptured Cerebral Aneurysm Study (UCAS) in Japan. It consists of patients with unruptured cerebral aneurysms enrolled between 2000 and 2004 at neurosurgical departments at tertiary care hospitals in Japan. The model was presented as a scoring system, and aneurysms were classified into 4 risk grades by predicted 3-year rupture risk: I, < 1%; II, 1 to 3%; III, 3 to 9%, and IV, >9%. The discrimination property and calibration plot of the model were evaluated with external validation data. They were a combination of 3 Japanese cohort studies: UCAS II, the Small Unruptured Intracranial Aneurysm Verification study, and the study at Jikei University School of Medicine., Results: The derivation data include 6,606 unruptured cerebral aneurysms in 5,651 patients. During the 11,482 aneurysm-year follow-up period, 107 ruptures were observed. The predictors chosen for the scoring system were patient age, sex, and hypertension, along with aneurysm size, location, and the presence of a daughter sac. The 3-year risk of rupture ranged from <1% to >15% depending on the individual characteristics of patients and aneurysms. External validation indicated good discrimination and calibration properties., Interpretation: A simple scoring system that only needs easily available patient and aneurysmal information was constructed. This can be used in clinical decision making regarding management of unruptured cerebral aneurysms., (© 2015 American Neurological Association.)

Objective: Blonanserin is a novel atypical antipsychotic drug that has efficacy equal to risperidone. We investigated the effects of aripiprazole and blonanserin on clinical symptoms and plasma levels of homovanillic acid (pHVA) and 3-methoxy-4hydroxyphenylglycol in the switching strategy of schizophrenia., Methods: Twenty two Japanese patients with schizophrenia were enrolled into this open study. The antipsychotics of all patients were switched to aripiprazole or blonanserin for the improvement of clinical symptoms or side effects. Plasma monoamine metabolites levels were analyzed with high-performance liquid chromatography., Results: There were no significant effects for time (p = 0.346) or time × group interaction (p = 0.27) on the changes of positive and negative syndrome scale (PANSS) total score, although blonanserin decreased PANSS scores. We observed negative correlation between pHVA at baseline and the change in PANSS total score (rs = -0.450, p = 0.046). We also found positive correlation between the changes in pHVA and the changes in PANSS total (rs = 0.536, p = 0.015) and positive (rs = 0.572, p = 0.008) scores., Conclusions: There were no differences between blonanserin and aripiprazole in the improvement of clinical symptoms. Our results suggest that pHVA may be useful indicator for the switching strategy to aripiprazole or blonanserin in schizophrenia., (Copyright © 2014 John Wiley & Sons, Ltd.)

Background: Recent reports have showed that some statins have protective effects in experimental cerebral aneurysm models. We conducted a case-control study to investigate an association between statin use and the rupture risk of cerebral aneurysm in Japanese population., Methods: This was a multihospital case-control study; cases and controls were collected from 15 hospitals in Japan. Cases consisted of patients with aneurysmal subarachnoid hemorrhage hospitalized from April 2009 to March 2011. Controls were selected from patients who had newly diagnosed unruptured saccular aneurysms from April 2006 to March 2011. The primary exposure of interest was statin use. Multivariable logistic regression was used to assess the relationship between stain use and the rupture risk of cerebral aneurysm., Results: A total of 117 cases and 304 controls were included in the analyses. Statin was used in 9.4% of cases and 26.0% of controls. Controls had a significantly higher rate of use of statin. The use of any statin was associated with cerebral aneurysm rupture after adjustment of potential confounders (adjusted odds ratio: .30, 95% confidence interval: .14-.66). The association was similar in each stratum of total cholesterol level., Conclusions: This observation from a hospital-based case-control study in Japan suggested that there is inverse relationship between use of statins and cerebral aneurysm rupture. Future clinical studies are needed., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background/aim: There have been many reports on the discomfort of speech when wearing oral appliances. Fricatives articulated in an oral cavity can be difficult to pronounce when oral appliances are worn, because the oral cavity is partially changed by their installation. Sibilant /s/, one fricative, is especially difficult to pronounce when wearing oral appliances. This study investigates the effect of the difference in the setting positions of the palatal margin of custom-made mouthguards on the aeroacoustic characteristics of sibilant /s/., Materials and Methods: Eighteen subjects (11 women and seven men) participated. The palatal margin of mouthguards was set at the gingival line for nine subjects and 4 mm from the line for another nine subjects. Acoustical analyses examined the difference of the palatal margins of the mouthguards on the autocorrelation coefficient, the zero crossing count, and the spectral peaks of sibilant /s/., Results: The results showed that the zero crossing count of the waveforms and the spectral peaks of sibilant /s/ were significantly broadened and shifted toward the low-frequency range with the mouthguard whose palatal margin extended 4 mm from the gingival line than the mouthguard whose palatal margin was set at the gingival line., Conclusion: We believe that a more appropriate palatal mouthguard design for custom-made mouthguards can be made by considering the aeroacoustical effects. Our study supported the mouthguard whose palatal margin was set at the gingival line by considering the influence on pronouncing sibilant /s/. We believe that a more appropriate palatal mouthguard design for custom-made mouthguards can be made based on the balance of aeroacoustical effects and mechanical requirements., (© 2012 John Wiley & Sons A/S.)

In 2010, the first Japanese edition of guidelines for the management of cutaneous lymphoma was published jointly by the Japanese Dermatological Association (JDA) and the Japanese Skin Cancer Society (JSCS) - Lymphoma Study Group. Because the guidelines were revised in 2011 based on the most recent data, we summarized the revised guidelines in English for two reasons: (i) to inform overseas clinicians about our way of managing common types of cutaneous lymphomas such as mycosis fungoides/Sézary syndrome; and (ii) to introduce Japanese guidelines for lymphomas peculiar to Asia, such as adult T-cell leukemia/lymphoma and extranodal natural killer/T-cell lymphoma, nasal type. References that provide scientific evidence for these guidelines have been selected by the JSCS - Lymphoma Study Group. These guidelines, together with the degrees of recommendation, have been made in the context of limited medical treatment resources, and standard medical practice within the framework of the Japanese National Health Insurance system., (© 2012 Japanese Dermatological Association.)

Communication between patients with cerebral aneurysms and consulting neurosurgeons remains unstudied in Japan. The present clinical study surveyed patients with unruptured cerebral aneurysms and their neurosurgeons after explanation of the disease and its treatment options and expected outcomes in clinic visits using a one-page written questionnaire about treatment options and decisions given to patients and their neurosurgeons. The numbers of participating patients and neurosurgeons were 42 and 9, respectively, and 42 paired patient-neurosurgeon responses were obtained. Agreement was quite low (κ = 0.17-0.31 for 6-point Likert scale and κ = 0.44-0.67 for 2 category scale) regarding the "best" treatment for each patient as agreed on by the patient and neurosurgeon. Agreement in the understanding of treatment options and general application was unexpectedly low (κ = 0.12 and 0.01 for 6-point Likert scale and κ = not applicable and -0.03, respectively, for 2 category scale). Agreement tended to be higher between experienced neurosurgeons and patients than non-experienced neurosurgeons and patients. Patients estimated much higher risks of stroke or death after surgical intervention (p < 0.001) or no intervention (p = 0.006) compared with the estimates offered by their neurosurgeons.

Background: Decision-making during the management of unruptured cerebral aneurysms is a delicate process for both neurosurgeons and patients. Guidelines are evidence-based references that can aid in making decisions. However, neurosurgeons do not always follow guidelines in clinical practice. The purpose of this study is to verify the hypothesis that there is substantial dissociation between treatment guidelines and practical decision-making due to a bias in treatment selection for unruptured cerebral aneurysms. This bias is dependent upon clinician-driven factors such as experience and specialty, and patient-driven factors such as patient preference., Methods: This study was performed using internet questionnaires. A total of 282 randomly selected, qualified Japanese neurosurgeons (out of approx. 6,000 registered neurosurgeons), including 45 endovascular specialists, participated in this study. Radiological and demographic data from 88 cases of unruptured cerebral aneurysm were opened on the Web. Participating neurosurgeons decided on the treatment for each case (clipping, coiling or observation)., Results: Variations in treatment selection were not significant between neurosurgeons and endovascular specialists, except for aneurysms such as anterior choroidal artery aneurysm. However, contrary to the guidelines, aneurysms larger than 10 mm tended to be treated conservatively because the risk of treatment is high, while aneurysms smaller than 5 mm in diameter were often selected for intervention (clipping or coiling)., Conclusions: This study revealed that in real-world clinical practice, physicians are not always faithful to the current guidelines. In making practical treatment decisions for unruptured cerebral aneurysms, the patient's will and the recognition of unavoidable, treatment-related risks seriously influence neurosurgeons' decisions., (Copyright © 2010 S. Karger AG, Basel.)

Background: Moyamoya disease (MMD) is an idiopathic steno-occlusive cerebrovascular disease that represents an important cause of stroke. However, etiology of the disease has remained largely unknown., Methods: We previously showed that the inheritance pattern of MMD is autosomal dominant with incomplete penetrance. Here, we report the genome-wide parametric linkage analysis for MMD in 15 extended Japanese families. We conducted linkage analyses under two diagnostic classifications: narrow and broad. Affected member-only analysis was applied due to incomplete and age-dependent penetrance of the disease., Results: Under both classifications, significant evidence of linkage was only observed on chromosome 17q25.3, with maximum multipoint logarithm of odds (lod) scores of 6.57 (under the narrow classification) and 8.07 (under the broad classification) at D17S704. Haplotype analysis revealed segregation of a disease haplotype in all families but one, and informative crossovers enabled mapping of the MMD locus to a 3.5-Mb region between D17S1806 and the telomere of 17q, encompassing 94 annotated genes., Conclusions: Our data suggest that there is a major gene locus for autosomal dominant moyamoya disease on chromosome 17q25.3.

Previous linkage analyses of intracranial aneurysm (IA) have proposed several genetic susceptibility loci; however, some loci remain contradictory. The objective of this study was to confirm these loci in a Japanese population using allelic and haplotype association analyses. We set high-density single nucleotide polymorphism markers in previously suggested IA loci and conducted an association analysis in 29 cases and 35 controls from a small community in Akita, Japan. Genotyping was carried out using the GeneChip 10 K mapping array, and the association analysis was performed using GeneSpring GT2 software. The result was confirmed in a replication cohort consisting of 237 cases and 253 controls from all over Japan. Only one variant, rs767603, at chromosome 14q23, was significantly associated with IA, both in allelic analysis (p=0.00017, Bonferroni-corrected p=0.021) and haplotype analysis (p=0.00178, Bonferroni-corrected p=0.048). This association was confirmed in the replication cohort (p=0.0046 for allelic association, p=0.0060 for haplotype association). Our findings confirm 14q23 to be a susceptibility locus for intracranial aneurysm.

Background and Purpose: In previous studies of familial intracranial aneurysm (IA), parametric linkage analyses have been undertaken for five unrelated families, four providing maximum logarithm of odds (LOD) scores with dominant models and one with a recessive model. Each family was linked to a distinct locus, indicating locus heterogeneity. This study aimed to examine whether Japanese IA families consistent with autosomal-dominant mode of inheritance support linkage to these loci., Methods: We performed genomewide linkage analysis using the GENEHUNTER program. Affected-only parametric linkage analysis was used for 41 affected members in nine unrelated IA families with dominant models, which were selected from 29 families used for a nonparametric (model-free) linkage analysis in our previous study., Results: We failed to support the linkage to previously reported autosomal-dominant loci. Instead, we found linkage to chromosome 19q13.3 with a maximum multipoint LOD score of 4.10. The LOD-1 interval (regions with LOD scores of >1) was 8.0 cM between D19S198 and D19S902., Conclusions: A genomewide scan for IA families with dominant models in Japan confirmed the locus at chromosome 19q13.3, which has also been reported as a candidate locus in a Finnish population.

Background and Purpose: Previous studies have shown positive evidence of linkage of the intracranial aneurysm (IA) at chromosome 7q11, 17cen, 19q13, and Xp22. These regions contain elastin (ELN), nitric oxide synthetase 2A (NOS2A), apolipoprotein E (APOE), and angiotensin-I converting enzyme 2 (ACE2), which are considered to be promising candidate genes for IA. We aimed to examine the association of single-nucleotide polymorphisms (SNPs) with IA in these candidate genes., Methods: To identify polymorphisms in NOS2A and ACE2, all exons and exon-intron boundaries were screened by direct sequencing in 30 randomly selected controls. The program tagSNPs was used to select an optimal set of haplotype-tagging SNPs. For ELN and APOE, SNPs were selected from previous reports. These selected SNPs were then genotyped in 362 cases with IA and 332 residential area matched controls. THESIAS software was used to investigate the association of alleles and haplotypes with IA by adjusting with covariates., Results: We genotyped 8 SNPs in ELN, 8 SNPs in NOS2A, 3 epsilon alleles in APOE and 1 SNP in ACE2. No alleles or haplotypes of 4 candidate genes revealed any significant association with IA., Conclusions: Investigated polymorphisms in this study were not associated with IA.