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Background: Limited national-level information on temporal trends in comprehensive stroke center (CSC) capabilities and their effects on acute ischemic stroke (AIS) patients exists. Aims: To examine trends in in-hospital outcomes of AIS patients and the prognostic influence of temporal changes in CSC capabilities in Japan. Methods: This retrospective study used the J-ASPECT Diagnosis Procedure Combination database and identified 372,978 AIS patients hospitalized in 650 institutions between 2010 and 2016. Temporal trends in patient outcomes and recombinant tissue plasminogen activator (rt-PA) and mechanical thrombectomy (MT) usage were examined. Facility CSC capabilities were assessed using a validated scoring system (CSC score: 1-25 points) in 2010 and 2014. The prognostic influence of temporal CSC score changes on in-hospitalmortality and poor outcomes (modified Rankin Scale: 3-6) at discharge were examined using hierarchical logistic regression models. Results: Over time, stroke severity at admission decreased, whereas median age, sex ratio, and comorbidities remained stable. During the study period, usage of rt-PA and MT in rural areas remained lower than that of urban areas, but in 2016, the differences in their use were within 1%. The median CSC score increased from 16 to 17 points. After adjusting for age, sex, comorbidities, consciousness level, and facility CSC score, proportion of in-hospitalmortality and poor outcomes at discharge decreased (from 7.6% to 5.0%, and from 48.7% to 43.1%, respectively). The preceding CSC score increase (in 2010-2014) was independently associated with reduced in-hospital mortality and poor outcomes, and increased rt-PA and MT use (odds ratio (95% confidence interval): 0.97(0.95-0.99), 0.97(0.95-1.00), 1.07(1.04-1.10), and 1.21(1.14-1.28) , respectively). Conclusions: This nationwide study revealed six-year trends in better patient outcomes and increased use of rt-PA and MT in AIS. In addition to lesser stroke severity, preceding improvement of CSC capabilities was an independent factor associated with such trends, suggesting importance of CSC capabilities as a prognostic indicator of acute stroke care.

Background and Purpose: Heart disease is a common comorbid condition among patients undergoing carotid endarterectomy (CEA) and carotid artery stent placement (CAS). However, the outcomes of patients with heart disease who were treated with CEA/CAS have not been fully examined. We investigated the impact of heart disease on outcomes of CEA and CAS in general practice using the Japanese nationwide data from J-ASPECT study. Methods: We analyzed data from 23,366 patients of CEA or CAS (CEA 8,514, CAS 14,809) who had been hospitalized in the period from April 2012 to March 2017. We extracted data from the Japanese nationwide DPC database for patients who underwent CEA or CAS which were identified from procedural coding with Japanese original K-codes (CEA: K6092, CAS: K609-2). For further categorization of carotid artery stenosis patients with or without heart disease, we used the ICD-10 code (ischemic heart disease, valvular disease cardiomyopathy, conduction disturbance, cardiac arrhythmia, atrial fibrillation/atrial flutter and heart failure) to identify the presence of heart disease. Outcome (death within 30days) was compared between the patient who underwent CEA or CAS and patient with or without heart disease after adjustment for patient characteristics by using the logistic regression analysis. Results: Of the patients who underwent CAS or CEA, 2495 (29.3%) in CEA and 3930 (26.5%) in CAS were complicated with heart disease. Heart disease was not associated with the risk of death within 30days in both patients undergoing CEA (OR, 1.38; 95% CI, 0.54-3.55, p=0.5) or CAS (OR, 1.42; 95% CI, 0.93-2.16, p=0.099). Among heart disease, valvular disease was associated with increased the risk of death within 30days in patients undergoing CEA (OR, 6.71; 95% CI, 1.89-23.77, p=0.0032) and CAS (OR, 2.94; 95% CI, 1.05-8.20, p=0.004) after adjustment for potential confounders. Especially of the patients with valvular disease, aortic valve disease was significantly increased the risk of death within 30days (CEA: OR, 11.2; 95% CI, 3.13-39.8, p=0.0002, CAS: OR, 3.53; 95% CI, 1.07-11.6, p=0.038). Conclusion: Patients who were complicated with valvular disease, especially aortic valve disease had a high risk of death within 30 days after CEA or CAS.

Objectives: To examine whether hospital case volume and comprehensive stroke centre(CSC) capabilities affect patient outcomes of clipping and coiling for subarachnoid haemorrhage (SAH). Methods: We conducted a nationwide retrospective cohort study. Using the J-ASPECT Diagnosis Procedure Combination database, we identified 27,490 SAH patients who underwent clipping or coiling in 621 institutions between 2010 and 2015. The CSC capabilities of each hospital were assessed using a validated scoring system (CSC score: 1-25 points). We classified the hospitals into quartiles based on CSC score and case volume of clipping or coiling for SAH. Results: In clipped patients, a high case volume ( > 14 cases / year) was significantly associated with reduced in-hospital mortality (Q1 as control, Q4 odds ratios (ORs) 0.71 [95% confidence interval 0.55 - 0.90]) but not poor outcome. In coiled patients, a high case volume ( > 9 cases / year) was associated with reduced in-hospital mortality (Q4 0.69 [0.53 - 0.90]) and poor outcomes (Q3 ( > 5 cases / year) 0.75 [0.59 - 0.96], Q4 0.65 [0.51 - 0.82]). A high CSC score ( > 19 points) was significantly associated with reduced in-hospital mortality of clipped (0.68 [0.54 - 0.86]) but not coiled patients. There was no association between CSC capabilities and poor outcomes. Conclusions: The effect of case volume and CSC capabilities on in-hospital mortality and short-term functional outcomes in SAH patients was different between clipping and coiling. In the modern endovascular era, better outcomes of clipping may be achieved in facilities with high CSC capabilities.

Background: The association between physician volume and the death rate for patients who are hospitalized for ischemic and hemorrhagic stroke remains unclear. It is unknown whether a volume threshold for such an association exists. We aimed to analyze the correlation between in-hospital stroke mortality and physician volume considering board certification status. Methods: For this cross-sectional study, data on patients hospitalized for ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) between 2010 and 2016[MOU1] [KN2] were obtained from the Diagnosis Procedure Combination database in Japan using International Classification of Diseases-10 diagnosis codes. The numbers of stroke care physicians and relevant board-certified physicians were asked. Odd ratios (ORs) of 30 day in-hospital mortality were estimated after adjustment for institutional differences, age, sex, comorbidities, and level of consciousness using generalized mixed logistic regressions. Findings: In a total of 295,150, 98,657 and 36,1741 patients with ischemic stroke, ICH and SAH, 30 day in-hospital mortality rates were 4.4,16 and 26.6 %. For all types of stroke, the number of stroke care physicians was associated with reduced in-hospital mortality (all p for trend Interpretation: The number of stroke care physicians was associated with reduced in-hospital mortality for all types of stroke. The volume threshold of board-certified physicians depends on specialty and stroke types.

Background: Improving the quality of stroke care is an urgent issue worldwide. To facilitate the measurement of quality of stroke care in Japan, we aimed to develop the Close The Gap-Stroke initiative in the J-ASPECT Study. Methods and Results: Quality indicators (QIs) were developed by a multidisciplinary board between 2015 and 2017. The process involved a systematic review of domestic and international studies related to primary and comprehensive stroke care. Adherence rates for the defined QIs were calculated for 8,826 patients with acute ischemic stroke from 227 hospitals between 2013 to 2015. Seventeen and 12 measures were identified as QIs for primary and comprehensive stroke care (PSC and CSC), respectively. We analyzed adherence rates of all 17 QIs for PSC and 8 QIs for CSC related with acute ischemic stroke. We found NIHSS documentation (91.0 %), CT/MRI performed within 25min and 24hr (80.9 % and 99.1 %), evaluation of extracranial vascular imaging (90.4 %), treated in stroke unit (57.4 %), tPA administration (89.5 %), tPA performed within 1hr (37.4 %), early and discharge antithrombotics medication (75.1 % and 49.0 %), discharge anticoagulation for atrial fibrillation patients (76.2 %), discharge statin medication (32.7 %), discharge antihypertensive agents (54.3 %), deep vein thrombosis prophylaxis (34.5 %), early rehabilitation (57.0 %), dysphagia screening (76.6 %), smoking cessation (59.8 %) and stroke education (71.4 %) for primary stroke care; and median time to multimodal CT or MR brain and vascular imaging (33 min), proper endovascular recanalization (81.7 %), tPA before endovascular recanalization (65.7 %), TICI grade 2b/3 after endovascular recanalization (73.0 %), median time of door to puncture (105 min), symptomatic intracranial hemorrhage after thrombolytic or endovascular therapy (7.45 %), 90 days mRS documentation after thrombolytic or endovascular therapy (60.8 %), occurrence of complication within 24 hours of diagnostic neuroangiography (7.27 %) for comprehensive stroke care. Conclusion: This is a promising first step to measure the QIs related to primary and comprehensive stroke care at a national level in Japan.

Background and purpose: In the rapidly aging society of Japan, improvement of the emergency medical care system for stroke is an urgent concern. In prehospital care for stroke, appropriate triage, selection of the delivery facility, and decreased transport time contribute directly to prognosis. The standard treatment for acute ischemic stroke (AIS) has changed dramatically. With the introduction of new thrombectomy devices, proper placement of comprehensive stroke centers (CSCs) should be reconsidered. Accordingly, a nationwide survey is needed to develop an efficient prehospital care system. The aim of this study was to elucidate problems in prehospital care for stroke in Japan, using a nationwide fire department (FD) questionnaire survey. Materials and methods: We conducted a questionnaire survey of 733 FDs in Japan with the cooperation of the Japanese Society of Emergency Medicine and the Emergency Planning Office of the Fire and Disaster Management Agency. The questionnaires evaluated utilization status of the Prehospital Stroke Life Support (PSLS) protocol and prehospital stroke scale (PSS), awareness of standard treatment with new devices, information on delivery facilities and transportation, use of information and communication technology (ICT), and the retraining system for paramedics. Results: Data obtained from 664 FDs (91%) were analyzed. The PSLS protocol and PSS were used by 47.2% and 59.6%, respectively. Surprisingly, only 35.6% of FDs had knowledge about the latest treatment for AIS, and half of the FDs did not have an opportunity to learn about treatment. The proportion of FDs with a CSC in their jurisdictions was decreased in rural areas compared with urban areas (19.2% vs. 49.8%). However, helicopter transportation and ICT were not adequately utilized even in rural areas. Only half of the FDs urged paramedics to attend a PSLS course. Conclusion: We demonstrated problems with prehospital care for stroke in Japan using a nationwide FD questionnaire survey. Placement of CSCs, adequacy of the transportation system, and communication between physicians and paramedics should be reevaluated.

Objective: We performed a nationwide study to evaluate the effectiveness of stent-retriever in addition to intravenous thrombolysis in acute ischemic stroke patients in the ‘‘real-world’’ settings. Methods: This was a retrospective cohort study using the Diagnosis Procedure Combination nationwide inpatient database in Japan. Patients with acute ischemic stroke who were admitted to hospitals between April 1, 2013, and March 31, 2014 were identified. The rate of functional independence (modified Rankin scale score, 0 to 2) at discharge and mortality at 30 days were compared between patients who received intravenous thrombolysis alone (IVT group) and those who received stent-retriever after intravenous thrombolysis (IVET group) using 1:1 propensity score-matching. Results: In total, 71,519 acute ischemic patients were identified in a year. Among those, 3,367 patients were eligible (3,110 in IVT group and 257 in IVET group). Post-matching, 134 pairs of patients were analysed. The rate of functional independence at discharge was higher in IVET group than in IVT group (odds ratio 1.96, 95% CI 1.16-3.35; p=0.012). In addition, there was no significant differences in mortality at 30 days between the two groups (odds ratio 1.80, 95% CI 0.81-4.23; p=0.153). Conclusion: This nationwide study revealed that mechanical thrombectomy with stent-retriever in addition to intravenous thrombolysis improves functional outcomes in patients with acute ischemic stroke, and with no evidence of increased mortality. A randomized clinical trial seems warranted.

Background: Many studies have reported that high-volume center was associated with the favorable outcomes in subarachnoid hemorrhage (SAH) patients with treatment. However, in Japan, the effect of the case volume of the hospital in SAH patients remains elusive. The aim of this study is to investigate the associations between case volume and outcomes of clipping or coiling using data obtained from the Japanese Diagnosis Procedure Combination [DPC]-based Payment System. Methods: Of the 847 certified training institutions of the Japan Neurosurgical Society, 327 institutions agreed to participate in this DPC discharge database study. Data on patients hospitalized for SAH between April 1, 2012 and March 31, 2013 were obtained from the DPC database. Patients hospitalized because of SAH were identified using International Classification of Diseases-10 diagnosis codes (I60.0-9). The case volumes of clipping and coiling in each hospital were divided into quintiles (Q1-Q4). Odd ratios (ORs) of in-hospital mortality and modified Rankin Scale (mRS) at discharge were estimated after adjustment for age, sex, comorbidities, and SAH severity. The category of Q1 was assigned a reference for OR. Results: A total of 5214 patients with SAH (3624 clipping, 1590 coiling) were analyzed. Mortality was 9.8%, and proportion of discharge mRS3-6 was 44.0%. No significant associations were found between case volume and in-hospital mortality in both the clipping (Q2, Q3, and Q4; OR = 0.97, 0.69, and 0.77; P = 0.902, 0.148, and 0.263) and coiling group (Q2, Q3, and Q4; OR = 0.94, 1.62, and 0.84; P = 0.864, 0.140, and 0.586). No significant associations were found between case volume and discharge mRS3-6 in both the clipping (Q2, Q3, and Q4; OR = 1.28, 1.27, and 1.09; P = 0.194, 0.189, and 0.619) and coiling group (Q2, Q3, and Q4; OR = 0.89, 1.15, and 0.78; P = 0.691, 0.599, and 0.315). Conclusion: In Japan, case volume did not show the correlation with outcomes in SAH patients. This nationwide database study reflects the real-world practice.

Introduction: Certification system of the primary and comprehensive stroke center (PSC and CSC) is still under discussion in Japan. This study attempts to examine associations between the variation of stroke center capabilities and the improvement of outcomes for acute ischemic stroke on a national scale. Hypothesis: Improvements in hospital stroke center capabilities leads to better outcome of acute ischemic stroke patients. Methods: Using a validated score for evaluating CSC capabilities, which consists of 5 categories (personnel, diagnostic techniques, specific expertise, infrastructure, and education) on a 25 point scale, we assessed CSC capabilities for 137 certified training hospitals in 2011 and 2015 (Kada et al. BMC Neurol 2017). A consecutive health insurance claims data known as the Japanese Diagnosis Procedure Combination/Per Diem Payment Systems of 2011 and 2015 was obtained from the hospitals. The proportion of favorable outcome—score 0 to 1 on the modified Rankin Scale (mRS)—at discharge was quantified as the primary outcome. The change in CSC score with more than two points over time was quantified as an independent variable. We regressed the change of CSC score on morbidity with adjustment of average age and sex in the hospitals. Results: In total, 18,658 in 2011 and 29,999 in 2015 ischemic stroke patients were admitted to 137 hospitals. Median annual number of ischemic stroke patients per hospital increased from 115 to 183 over time. Mean age (74.5 year vs 74.2 years) and proportions of men (56.8% vs 58.2%) were almost the same. The mean CSC scores increased from 15.9±4.0/25 to 17.2±4.2/25 point. The mean hospital mortality decreased from 6.1% to 4.3%. The mean proportion of patients with the favorable outcome at discharge increased from 39.2% to 45.5%. We selected random-effect model based on Housman test. In regression analyses, the increase of CSC score over time was significantly associated with the increasing proportion of the favorable outcome at discharge (coefficient, 2.76; 95% CI, 0.04-5.47; p-value, 0.047). Conclusions: Improvements in CSC capabilities overtime was significantly related to the improvement of functional outcome at discharge in ischemic stroke patients.

Introduction: In recent years, the treatment of the acute phase of cerebral infarction such as tPA and endovascular thrombectomy has been rapidly changing, and development of a medical system for acute cerebral infarction is desired. Objective: To examine the effect of tPA and endovascular thrombectomy on mortality in patients with acute ischemic stroke in the nationwide 5 years hospital cohort in Japan. Methods: We conducted annual nationwide survey from 2011 to 2015 using data from the Japanese Diagnosis Procedure Combination database on patients hospitalized with ischemic and hemorrhagic stroke in a nationwide hospital cohort in Japan (J-ASPECT Study). The effect of tPA or endovascular thrombectomy on stroke mortality was analyzed by mixed effect model with years (from 2011 to 2015), age, gender, Japan Coma Scale (JCS), and Comprehensive stroke care (CSC) score as a fixed effect, and hospital as a random effect. CSC score was developed by our study group based on the institutional survey conducted in 2011. Results: The total numbers of patients were 292,230 in ischemic stroke. In 5 years, the proportion of tPA or endovascular thrombectomy has increased from 7.2% to 8.4%, while the mortality has decreased from 7.6% to 5.5%. The mortality varied by JCS, which was 37.5% for JCS 3 digit, 15.4% for JCS 2 digit, 4.8% for JCS 1 digit and 1.4% for JCS 0 in 2015. In the analysis of subjects with severe JCS 3 digit, years (OR = 0.97, 95% CI = 0.94 - 1.00), CSC score increase (0.98, 95% CI = 0.97 - 0.99), and tPA or endovascular thrombectomy (OR = 0.75, 95% CI = 0.67 - 0.84) were found to reduce the risk of death. Conclusion: According to the analysis of patients with acute ischemic stroke for 5 years, tPA or endovascular thrombectomy was related to reduced mortality in subjects with high severity.

Objective: We previously demonstrated comprehensive stroke care (CSC) capabilities of the hospitals affect in-hospital mortality of patients with acute stroke. With the advent of unprecedented aging society, proper implementation of stroke centers requires understanding of geographical disparity of patient characteristics as well as stroke care capabilities. The aim of this study was to elucidate such geographical disparity regarding acute stroke care in Japan using a nationwide database. Materials and methods: We analyzed the data obtained from the Japanese Diagnosis Procedure Combination-based Payment System in 445 institutions between 2010 and 2012. Patients hospitalized emergently for ischemic stroke(IS), non-traumatic intracerebral hemorrhage(ICH) and non-traumatic subarachnoid hemorrhage(SAH) were identified using International Classification of Diseases-10 diagnosis codes. We classified the location of the hospitals into 4 areas, “Metropolitan Employment Area-Central (MEA-C)”, “ Metropolitan Employment Area-Outlying (MEA-O)”, “Micropolitan Employment Area-Central (McEA-C)”, and “ Micropolitan Employment Area-Outlying (McEA-O)”. We investigated patient characteristics, medical backgrounds, interventions and outcomes for each area. Results: Data obtained from a total of 214,910 patients with acute strokes (136,753 IS, 60,379 ICH and 17,778 SAH) were analyzed. As for patient characteristics, elderly patients and those with hypertension were more common in McEA-C and McEA-O, and stroke severity was more severe in McEA-C in all stroke types. As for hospital characteristics, proportion of admission by ambulance and CSC capabilities of the hospitals were smaller in all stroke types. Moreover, emergent interventions such as intravenous rt-PA infusion were performed at a lesser extent and in-hospital mortality was higher in McEA-C and McEA-O, and severe disability with mRS 3-6 was more often noted in McEA-C in all stroke types. Conclusion: We demonstrated geographical disparity of acute stroke care in Japan from a nationwide database. For proper implementation of stroke centers, centralization of acute stroke care capabilities should be considered in the rural areas to improve outcomes of acute stroke.

Objective: This study aimed to investigate recent nationwide trends in the epidemiology of acute ischemic stroke (AIS) in Japan. Methods: We analyzed 328,147 acute ischemic stroke patients in 350 certified training hospitals in Japan using data obtained from the Japanese Diagnosis Procedure Combination Database. Data between the period April 1, 2010 and May 31, 2014 were used. We divided patients into three treatment groups: medical treatment only (group M), intravenous t-PA infusion only (group IVT), and endovascular treatment (group ET). Outcome was assessed by in-hospital mortality and modified Rankin Scale (mRS) score at discharge, and poor outcome was defined as a mRS score of 3-6. Results: The patient proportion in groups M, IVT, and ET changed from 94.3%, 3.2%, and 1.6% in 2010 to 90.9%, 4.3%, and 3.7% in 2014, respectively (P Conclusion: In Japan, during the 5-year period before the guidelines concerning proper use of ET for AIS were revised in 2015, a significant improvement in in-hospital mortality and functional outcomes of AIS patients undergoing medical treatment and intravenous rt-PA infusion was observed. This was probably due to a gradual increase in the proportion of patients undergoing IVT; the outcomes of ET, however, remained the same.

Introduction: Reports on hospital-specific, risk-standardized outcomes using claims data on acute ischemic stroke are increasing. However, these reports sometimes fail to account for stroke severity. Hypothesis: Hospital-specific, risk-adjusted mortality rating without accounting for stroke severity are altered after including initial severity for ischemic strokes. Methods: The health insurance claims data known as the Japanese Diagnosis Procedure Combination/Per Diem Payment Systems between April 1, 2013 and May 31, 2014 was obtained from 332 certified training institutions in Japan. The hospital-specific, risk-adjusted 30-day mortality rate was calculated using a hierarchical logistic regression model. We developed two models, with and without initial levels of consciousness (LOC), and compared them to assess the impact of stroke severities on hospital-specific mortalities. The hospital-specific mortalities with and without LOC were ranked and groped into 3 categories (top 20%, middle 60%, and bottom 20%), and then compared across the two models. We used an integrated discrimination improvement (IDI) index to measure how the model with LOC reclassified patients compared with the model without LOC. Patients with deep comas were excluded from the analyses. Results: We analyzed 64,569 acute ischemic stroke patients. Crude 30-day mortality was 3.9% , the mean age was 74.1±1.3 years, 41.2% were women, 70.8% had hypertension, 29.2% had diabetes mellitus, 79.9% had a Charlson comorbidity index score greater than 5, 3.7% had severe LOC (coma/semi-coma) and 8.1% had modestly impaired LOC. Among hospitals ranked in the top 20% of performers without LOC, 26.9% were ranked in the middle 60% when LOC was adjusted. Among the bottom 20% of performers without LOC, 21.2% were ranked in the middle 60% when LOC was adjusted. The hospital-specific, risk-adjusted 30-days mortality model with LOC had a significantly better IDI index score than the model without LOC (IDI, 0.09; P Conclusions: Adding the metric of stroke severity to a hospital-specific, risk-adjusted 30-day mortality model based on claims data was associated with model improvement and changes of mortality-based performance rankings.

Background: The effectiveness of comprehensive stroke center (CSC) capabilities on outcome of carotid endarterectomy (CEA) and carotid artery stenting (CAS) remains uncertain. We performed a nationwide study to examine whether CSC capabilities influenced in-hospital outcome of CEA and CAS. Methods: We analyzed 12,943 carotid artery stenosis patients treated with CEA or CAS in 350 certified training hospitals in Japan. Data between April 1, 2013 and May 31, 2015 was obtained from Japanese Diagnosis Procedure Combination Database. Among the institutions that responded, outcome was assessed by in-hospital mortality, ischemic stroke and myocardial infarction. CSC capabilities were evaluated from the 749 certified training institutions in Japan, which responded to a questionnaire survey regarding CSC capabilities that queried the availability of personnel, diagnostic techniques, specific expertise, infrastructure, and educational components recommended for CSCs. Total CSC scores of the participating hospitals were classified into quartiles (Q1: 0-15, Q2: 16-17, Q3: 18-19, Q4: 20-24). Results: The proportion of CEA and CAS were 5068 and 7875 (2013: 1685 and 2590, 2014: 1668 and 2564, 2015: 1715 and 2721). Between CEA and CAS, mortality rates were 0.24% and 0.75%, ischemic stroke were 8.41% and 7.56% and myocardial infarction were 0.76% and 0.17%. These outcomes had no differences among the years. There was tendency that mortality rates were lower with high total CSC scores in patients with CEA (Q1: 0.42%, Q2: 0.26%, Q3: 0.12%, Q4: 0%, P=0.16), but there were no differences with CAS (Q1: 1.0%, Q2: 0.74%, Q3: 0.63%, Q4: 0.83%, P=0.73). Ischemic stroke were significantly lower with high CSC scores in CEA (Q1: 9.76%, Q2: 10.77%, Q3: 9.14%, Q4: 6.59%, P Conclusion: It is reported using the data of Nationwide Inpatient Sample that operator volume was an important predictor of postprocedural outcomes in CAS. We demonstrated that CSC capabilities were associated with reduced in-hospital ischemic stroke in patients with CEA and CAS.

Background and purpose: The incidence of non-traumatic intracranial hemorrhage (ICH) during treatment with direct oral anticoagulants (DOACs) is lower than that during warfarin treatment. The characteristics of intracranial hemorrhage during DOAC therapy, however, remain unclear. Therefore, we performed a nationwide survey in Japan to examine the clinical characteristics and outcomes of DOAC-associated ICH using data obtained from the Japanese Diagnosis Procedure Combination (DPC)-based Payment System. Methods: We analyzed the data of 1,567 patients with ICH (DOAC-associated ICH, 88; warfarin-associated ICH, 1,479) who were urgently hospitalized at 575 institutions across Japan from April 2010 to March 2013 for whom prescription data before admission were available. Results: The annual number of patients with all anticoagulant (DOAC or warfarin)- associated ICH in each year from 2010 to 2013 was 226, 252, 426, and 663, representing 15.7%, 15.4%, 16.1%, and 16.1% of all ICH cases in the same period, respectively. There was an increase in the proportion of patients who presented with DOAC-associated ICH in all anticoagulant-associated ICH in each year from 2010 to 2013 (0%→0.4%→3.8%→10.7%). The proportion of patients with impaired consciousness (three-digit score on Japan Coma Scale) at admission (DOAC, 19.3%; Warfarin, 25.4%; P=0.20), in-hospital mortality within 7 days (DOAC, 11.4%; Warfarin, 19.5%; P=0.06), and mRS score of 5-6 at discharge (DOAC, 27.3%; Warfarin, 37.4%; P=0.06) were lower in the patients with DOAC-associated ICH. The rates of surgery for hematoma removal were significantly lower in the patients with DOAC-associated ICH (NOAC, 2.3%; Warfarin, 9.7%; P=0.019). Conclusions: This is the largest nationwide study of DOAC-associated ICH in a real-world situation in Japan, revealing that the patients with DOAC-associated ICH had better clinical outcomes compared with warfarin-associated ICH, probably due to milder hemorrhage at admission.

Background and purpose: The outcomes of subarachnoid hemorrhage (SAH) in aged patients are more severe than those in non-aged patients. There are few reports about the relationship between the age and the effect of perioperative care for SAH patients. We performed a nationwide survey in Japan to determine the relationship between perioperative care and SAH outcomes in aged and non-aged patients. Methods: We analyzed 17,343 subarachnoid hemorrhage (SAH) patients treated with clipping or coiling in 579 hospitals who participated in the J-ASPECT study. Data between 2010 and 2013 were obtained from the Japanese Diagnosis Procedure Combination Database. We stratified patients into two groups according to their age (aged group >75 y.o., n=3885; non-aged group < 75 y.o., n=13,458) and analyzed the association between perioperative care and poor outcome (modified Rankin Scale score 3-6 at the time of discharge). With respect to perioperative care, we evaluated time from onset to surgery (days), treatment (clipping or coiling), and drugs delivered after surgery (fasudil hydrochloride, ozagrel sodium, cilostazol, statin, EPA, edaravone). Results: In the non-aged group, coiling (OR=0.84; P Conclusion: Coiling and treatment with fasudil hydrochloride, statins, and EPA improved outcomes of non-aged patients. Although perioperative care did not improve the outcome of aged SAH patients, in cases of relatively mild SAH, perioperative care had the potential to improve the outcome.

Introduction: Higher hospital volumes have been related to better outcomes in previous researches. However, the mechanisms of the volume-outcome relationships in stroke have not been sufficiently figured out. The aim of this study is to uncover the roles of processes in acute phase stroke care among the volume-outcome relationships. Hypothesis: Processes of care mediate the volume-outcome relationships in stroke patients. Methods: We analyzed 45,598 acute ischemic stroke patients in 267 certified training hospitals in Japan. Data between April 1,2011 and May 31, 2012 was obtained from Japanese Diagnosis Procedure Combination Database. We divided annual hospital case volumes into two groups: high-volume and low-volume. Main outcome was 30-day mortality. We set following process of care as mediators: early initiation of aspirin prescription (less than 24 hours) and early initiation of stroke rehabilitation (less than 3 days). Multilevel mediation models were performed adjusting for age, gender, comorbidities, Charlson comorbidity index to examine the relationships among hospital volume, processes of care and outcome. Results: The early initiation of aspirin increased from 19.4% to 24.1%, the early initiation of rehabilitations increased from 59.6% to 65.6% and 30-day mortality decreased from 6.1% to 4.2%, for low-volume and high-volume hospitals. In the multilevel logistic regression analyses, admission to high-volume hospitals had 38% increased odds (OR = 1.38; 95% CI, 1.02-1.88) and 118% increased odds (OR = 2.18; 95% CI, 1.59-2.98) of early aspirin and rehabilitation initiation, compared with low-volume hospitals. Before adjusting for processes of care, admissions to high-volume hospitals had 30% decreased odds of death compared with admission to low-volume hospitals (OR = 0.70; 95% CI, 0.61-0.81). When processes of care were further adjusted, the volume-mortality relationship became non-significant. The early initiation of aspirin and rehabilitation accounted for 71% of the relationship (the regression coefficient was reduced from -0.355 to -0.102 when adjusted for processes of care). Conclusions: Processes of care mediated the volume-outcome relationships in stroke patients.

Introduction: Organized stroke care is an integrated approach to managing stroke to improve outcomes. However, the effectiveness of organized stroke care on mortality and morbidity remains uncertain. This study aimed to examine whether Organized stroke care index (OCI), which graded 0-3 based on the presence of rehabilitation, stroke team assessment, and admission to a stroke unit, developed to assess the accessibility to stroke care by Saposnik (Neurology 2010) influenced stroke outcomes in a nation wide hospital cohort. Hypothesis: OCI influenced mortality and morbidity of patients with ischemic and hemorrhagic stroke. Methods: Of the 1369 certified training institutions in Japan, 749 hospitals responded to a questionnaire survey regarding comprehensive stroke care capacities. Among the institutions that responded, data on patients hospitalized between April 1, 2010 and March 31, 2014, because of stroke were obtained from the Japanese Diagnosis Procedure Combination database. In-hospital mortality morbidity was analyzed using hierarchical logistic regression analysis adjusted for age, sex, level of consciousness on admission, Charson Score and the number of OCI fulfilled in each component and in total. Results: Data from 265 institutions and 220,027 emergency-hospitalized patients were analyzed. Patients fulfilled the criteria for admission to a SCU, stroke team assessment and the presence of rehabilitation were 29.9%, 41.2% and 66.5%, respectively. Mortality adjusted for age, sex, Charson score and level of consciousness was significantly correlated with admission to a SCU (OR=0.83, p Conclusion: A strong association between organized stroke care and lower mortality was apparent. These data suggest that organized stroke care should be provided to stroke patients regardless of stroke subtype.

Objective: Recommendations for comprehensive stroke centers (CSC) have been launched, but evaluations of these with respect to accessibility and mortality have not been clear. We thus examined the relationship between stroke centers and transfer time on mortality of subarachnoid hemorrhage (SAH) from a nationwide survey: J-ASPECT Study in Japan. Methods: We approached 1,369 certified training institutions in Japan with a survey regarding acute stroke care capabilities, and 749 hospitals responded. The CSC score was generated to evaluate the capabilities of CSC (Iihara K et al. PLOS One 2014). Data for patients hospitalized with stroke were gathered from the Japanese Diagnosis Procedure Combination database from April 1, 2010 to May 31, 2012. Transfer time was measured using an electronic mapping system based on patients’ postal addresses and hospitals. We examined the effects of CSC scores on mortality using instrumental variable analysis with log-transferred transfer time as an instrumental variable, adjusted by age, gender, and scores of the Japan coma scale (JCS) which was grading with the 1-, 2-, and 3-digit codes (Iihara K et al. PLOS One 2014). Results: Data from 265 institutions and 9,648 emergency-hospitalized patients with SAH were analyzed. Mortality rate was 28.8% and median transfer time was 22 min. Longer transfer times were associated with high CSC scores (p < 0.001). Adjusting for log-transformed transfer time, high CSC scores corresponded to lower mortality in patients with SAH, and the adjusted difference between high and low scores was 25.6% (95%CI= 8.5 - 42.6%). The severe SAH patients with JCS of 2- or 3-digit code showed more influence of CSC score on mortality, and the difference was 33.5% (95%CI= 21.5 - 45.5%). Conclusion: Longer transfer times were associated with the choice of highly qualified stroke centers measured by CSC scores, and highly qualified stroke centers were associated with lower mortality of SAH.

Objective: The nation-wide mortality and morbidity of carotid endarterectomy (CEA) and carotid artery stenting (CAS) on asymptomatic internal carotid artery stenosis in Japanese have not been clear. We thus examined the comparison of CEA and CAS from a nationwide survey in Japan. Methods: Certified neurosurgical training institutions in Japan provided data from the DPC database on patients hospitalized with neurosurgical diseases between April 1, 2012 and March 31, 2013. Patients hospitalized owing to asymptomatic internal carotid artery stenosis (ICS) for male patients were identified from the DPC database based on the International Classification of Diseases (ICD)-10 diagnosis code (I65). We excluded patients with emergency admissions. We compared the mortality rates, modified Rankin Scale (mRS) scores, and postoperative complications who underwent CEA and CAS based on propensity score matching. A propensity-matched cohort was constructed with CEA group and CAS group matched on a 1:1 basis by a nearest neighbor matching method within a caliper 0.05 SD of the propensity score for age, Charlson score, BMI and admission conscious level. Result: We identified 2216 patients with asymptomatic ICS (1381 CAS and 835 CAS cases). After propensity matching, Patient characteristics (age, hypertension, DM , hyperlipidemia, smoking and Charlson score) were well balanced between two groups. Patients who underwent CAS had a significantly lower number of complications than patients who underwent CEA (delta= -9.74; P < 0.001).Length of hospital stay was significantly shorter for CAS group. (delta= -9.90; P < 0.001). 30 day mortality and mRS at discharge were not significantly different between two groups. Conclusions: Our results estimate the baseline national rates of outcomes in patients with asymptomatic ICS that were treated with CAS or CEA in Japan. CAS treated group showed lower complication rates compared to CEA treated group.

Warfarin is an efficacious anticoagulant because it can be tailored for therapy using PT-INR. However, highly variable interindividual dosing requirement becomes a problem in empirical dosing or dosing using only clinical characteristics. Thus, several pharmacogenetics-guided algorithms (PGAs) have been proposed. We aimed to establish a PGA including factors of renal impairment and vitamin K (VK) intake and to evaluate its efficacy for more accurately predicting individual warfarin dose in genetically homogeneous population. We studied a single-center prospective cohort study of 176 Japanese patients on stable, therapeutic doses of warfarin to establish a PGA in which VK intake and renal impairment were considered to predict individual maintenance dose. We used another data set of 157 Japanese patients obtained from a multicenter prospective cohort study and compared our results with the results of 2 previously proposed PGAs applied to the same database; one, from the International Warfarin Pharmacogenetic Consortium (IWPC) (N Engl J Med, 2009), which considered race (but not renal function or VK intake), and the other reported by Limdi et al. (Am J Kidney Dis, 2010), which considered renal function (but not race or VK intake). Genotyping results showed that 80% patients had the homozygotes of CYP2C9 wild-type allele and VKORC1 -1639A variant, indicating the high genetic homogeneity in Japanese population. The mean observed maintenance doses (3.17 ± 1.09 mg/day) was compatible with that estimated by our algorithm (O: 3.13 ± 0.97) but was higher or lower than that by IWPC (I: 2.65 ± 0.71) or Limdi (L: 5.36 ± 0.92), respectively, although all algorithms showed similar coefficients of determination (O: 0.62, I: 0.67, L: 0.61). Our algorithm also revealed excellent results compared with others in terms of mean absolute error (O: 0.67 ± 0.63 mg/day, I: 0.75 ± 0.60, L: 2.19 ± 0.88) and the percent of patients whose doses were estimated within ±1.0 mg/day of the observed maintenance dose (O: 77.5%, I: 73.3%, L: 9.0%).Race seemed to be one of the most critical factors for PGA, and PGA including VK intake and renal impairment as factors appeared to be more accurate to predict individual warfarin dose in a genetically homogenous population such as Asians.

Background and Purpose: The effectiveness of organized stroke care on stroke mortality and morbidity remains uncertain. We examined whether organized stroke care index (OCI), which graded 0-3 based on the presence of rehabilitation, stroke team assessment, and admission to a stroke unit developed by Saposnik (Neurology 2010) influence in-hospital mortality and morbidity of patients with ischemic and hemorrhagic stroke in a nationwide study. Methods: Of the 1369 certified training institutions in Japan, 749 hospitals responded to a questionnaire survey regarding comprehensive stroke care capacities. Among the institutions that responded, data on patients hospitalized between April 1, 2010 and March 31, 2011, because of stroke were obtained from the Japanese Diagnosis Procedure Combination database. In-hospital mortality morbidity was analyzed using hierarchical logistic regression analysis adjusted for age, sex, level of consciousness on admission, and the number of OCI fulfilled in each component and in total.It was supported by Grants-in-Aid from the Ministry of Health, Labour and Welfare of Japan Results: Data from 265 institutions and 53,170 emergency-hospitalized patients were analyzed. Patients fulfilled the criteria for admission to a SCU, stroke team assessment and the presence of rehabilitation were 28.9%, 42.1% and 95.1%, respectively. Mortality adjusted for age, sex, and level of consciousness was significantly correlated with admission to a SCU (OR=0.87, p=0.039), SCU team assessment (OR=0.88,p=0.029), and OCI ( OR=0.93, p=0.031). Modified ranking scale 0 to 2 rate were also associated with significantly SCU admission (p=0.003) .These association holds for ischemic stroke and subarachnoid hemorrhage. Conclusion: A strong association between organized stroke care and lower mortality was apparent. These data suggest that organized stroke care should be provided to stroke patients regardless of stroke subtype.

[Background] The patients with penetrating artery territory infarction (PATI) sometimes show progressive motor deficits during the acute stage with poor prognosis. Although some predicting factors are suggested concerning symptomatic progression (SP), there have been no established predicting indices and medical therapy to suppress SP. In this study, we investigated the clinical factors including medical therapy related with SP in PATI . [Methods] We retrospectively examined acute stroke patients with PATI for recent two years in collaborative hospitals. SP was defined as the increase of at least one point on the National Institutes of Health Stroke Scale (NIHSS). The influence of factors including age, sex, medical history, vital signs and laboratory data on admission, and medical therapies, on SP were determined by multivariable logistic regression. [Result] Five hundreds and eight patients (320 men with a mean age of 70 years) with PATI were consecutively enrolled. The mean modified Rankin scale (mRS) before the onset was 0, and average NIHSS score on admission (adNIHSS) was 3. Sixty six patients (13%) exhibited SP. On univariable analysis, the following factors were risk factors of SP: adNIHSS, systolic blood presseure on admission (adsBP), BUN, HbA1c, LDL-C. Dual antiplatelet therapy (DAPT) was administered to more patients with SP than to those without SP within 24 hours after admission. Outcome measure using mRS at 3 months after ictus was worse in patients with SP than in those without SP (3 vs 1, p [Conclusions] In our retrospective study, more than 10% of patients with PATI showed progressive course in the acute stage with poor prognosis despite the best available therapy. Initial high blood pressure, diabetic and dehydration tendency on admission influenced the early progression in penetrating artery territory cerebral infarction with poor outcome.

Background: Vitamin K epoxide reductase (VKORC1) and cytochrome p450 isoform (CYP2C9) genotypes contribute to basal therapeutic warfarin doses. Although safe introduction of warfarin is possible, prothrombin time-international normalized ratio (PT-INR) fluctuations requiring continuous adjustment of warfarin doses have been observed in the same patient. Of late, nongenetic factors, in particular renal function, have been associated with warfarin maintenance dose and decreased anticoagulation stability; however, the mechanism of decreased anticoagulation stability has not been identified. This study aimed to elucidate the factors that affect basal and fluctuating warfarin maintenance doses. Methods: This study was a prospective, multicenter, observational study. Patients who were prescribed warfarin for thromboembolism were enrolled. Patient characteristics and CYP2C9 and VKORC1 genotypes were recorded. To evaluate anticoagulation stability and patient management, we measured PT-INR, estimated creatinine-based GFR (eGFR), and vitamin K intake and examined the warfarin maintenance doses and requirement of warfarin dose change four times a year (seasonally). Vitamin K intake was assessed by a semi-quantitative food frequency questionnaire. Multivariate logistic regression analysis was used to determine the factors affecting basal warfarin doses and PT-INR fluctuations or the necessity of adjustment of warfarin dose. Results: We analyzed the data of 327 patients. Genotyping results of CYP2C9 and VKORC1 showed that 80% patients had wild type CYP2C9 and the AA genotype of VKORC1 . eGFR was 63.2 ± 18.0 ml/min/1.73 m 2 . Vitamin K intake was 100.0 ± 60.9 μg/day in spring, 91.5 ± 53.8 μg/day in summer, 98.5 ± 69.1 μg/day in autumn, and 108.3 ± 67.0 μg/day in winter. Multivariate analysis showed that age, body surface area, eGFR, and genetic subtypes affected basal warfarin maintenance dose (p < 0.05). Furthermore, except seasonal variation in vitamin K intake, no other factor affected PT-INR fluctuation or the necessity of adjustment of warfarin dose. Conclusion: Age, body surface area, eGFR, and genetic subtypes affected basal maintenance warfarin dose; however, except vitamin K intake, no other factor affected warfarin dose fluctuation.

Objective Weekend disparities in stroke care were well known. The aim of this study is to examine the association between day of admission and the mortality of Stroke in Japan. Moreover, we examine if comprehensive stroke center (CSC) could overcome the weekend effect. Methods We analyzed the Nationwide registry of claim data(J-ASPECT study) in 378 certified training institutions of the Japan Neurosurgical Society and/or the Japan Stroke Society, which included patients discharged with a primary diagnosis of cerebral infarction in 2011. The definition of CSC was followed by the article of McKinney et al. (Stroke. 2011;42:2403-2409.) Results A total of 68,718 patients were admitted with a primary diagnosis of cerebral infarction during the study period while 10,141 patients were admitted to comprehensive stroke centers. As a result, thirty-day mortality was statistically greater in patients admitted on weekends compared to weekdays (9.1% versus 8.3%; P = 0.0004). The age and sex adjusted risk of death at 30 days which derived from multivariate logistic regression were also significantly greater for weekend admission (odds ratio, OR= 1.11; 95% CI, 1.04 to 1.18). This association was robust using hierarchical logistic regression which adjusted for institute difference. (OR= 1.06, 95% CI, 1.01 to 1.12) .The mortality of patients in hospitals with stroke care units showed no difference between weekends and weekdays (p=0.398) while the difference was significant for patients, not in a stroke care unit (p=0.046).Furthermore, there was no significant difference in 30-day mortality for patients admitted to CSCs between weekends and weekdays (p=0.418) while patients who were not admitted to CSCs showed the significant mortality difference between weekends and weekdays (p=0.041). The risk of mortality was 2% decreased with the satisfaction of every one criterion for comprehensive stroke care unit. (OR=0.98, 95% CI 0.97 to 0.99) adjusted for weekend effect. Conclusions Patients with stroke admitted on weekends in Japan had a significantly higher risk of death than weekdays within 30 days. There was no significant weekend difference of stroke mortality at hospitals with stroke care units and comprehensive stroke centers.