Background Stroke thrombolysis with alteplase is currently recommended 0-4•5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4•5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis.Methods In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4•5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. FindingsWe identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1•86, 95% CI 1•15-2•99, p=0•011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9•7, 95% CI 1•23-76•55, p=0•031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1•55, 0•81-2•96, p=0•66).Interpretation Patients with ischaemic stroke 4•5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis.

the Taiwan Stroke Registry InvestigatorsBackground-Stroke is a leading cause of death around the world. Improving the quality of stroke care is a global priority, despite the diverse healthcare economies across nations. The American Heart Association/American Stroke Association Get With the Guidelines-Stroke program (GWTG-Stroke) has improved the quality of stroke care in 790 US academic and community hospitals, with broad implications for the rest of the country. The generalizability of GWTG-Stroke across national and economic boundaries remains to be tested. 2,3 This was followed by the implementation of the American Heart Association/American Stroke Association Get With the Guidelines-Stroke program (GWTG-Stroke). 4 GWTG-Stroke was the first large-scale nationwide assessment of the quality of stroke care based on a set of predefined performance measures. The 790 participating hospitals showed substantial and sustained improve- Clinical Perspective on p 1123Stroke is the second leading cause of death globally, 5 with nations with diverse health care systems facing a similar medical and economic burden. 6 Whether the successful GWTG-Stroke is applicable beyond the United States remains to be tested. A key determinant that may hamper broad application of GWTG-Stroke around the world is the diversity of healthcare economies. It could be difficult for nations spending substantially less in healthcare dollars to apply GWTG-Stroke standards. To examine whether GWTGStroke is workable across nations with substantial disparities in health expenditures, we applied GWTG-Stroke to assess the quality of stroke care in Taiwan. Like the United States, stroke is the third leading cause of death in Taiwan. In 2008, the total cost of stroke in the United States, with 780 000 new or recurrent stroke cases, was estimated to be $65.5 billion, with direct (medical) costs constituting two thirds or $43.6 billion. 5 Taiwan, with a population of 23 million (1/13 of that of the United States), with Ϸ80 000 new or recurrent strokes a year, spent a total of US $375 million in medical costs for stroke in 2007. 7 The total medical costs per new or recurrent stroke patient were Ϸ1/10 of those spent in the United States. 5 The Taiwan Stroke Registry (TSR) is an appropriate program to assess the generalizability of GWTG-Stroke across national as well as economic boundaries. TSR, sponsored by the Department of Health (DOH), was launched in 2006. With the exception of anticoagulation for deep vein thrombosis (DVT) and measures for smoking cessation, all the parameters adapted by GWTG-Stroke for assessing quality of stroke care have been included in TSR. Methods TSR Design and the Criteria for Hospital SelectionTSR is the first nationwide effort in Taiwan to establish a reliable national stroke database for assessing the quality of stroke care and identifying areas that require improvement. TSR was designed and a TSR operation manual developed after a series of consensus conferences attended by an expert panel (16 stroke neurologists and 2 epi...

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CHADS2 and CHA2DS2-VASc scores were predictive of postoperative atrial fibrillation after cardiac surgery and may be helpful for identifying high-risk patients.

Background and Purpose-Of few prospective studies that have focused on the relationship between fibrinogen and ischemic stroke (IS) in Asian populations, the findings were inconsistent with those conducted in Western countries. Therefore, we aimed to investigate the temporal relationship between fibrinogen levels (plus several related parameters) and IS in a community-based study in Taiwan. Methods-Baseline data from 3281 adults (Ն20 years of age) in the Cardiovascular Diseases Risk Factor Two-Township Study were linked to incidental IS status derived from insurance claims and death certificate records. Hazard ratios and 95% CIs of clotting factors (fibrinogen, factor VII, factor VIII, and antithrombin-III) for IS events were estimated using Cox proportional hazard models. Results-With 10.4 years (average) follow-up, 128 persons developed IS (3.75 per 1000 person-years). As expected, elevated blood pressure and diabetes were independent predictors of IS events. A dose-response relationship was found in univariate analysis between IS risk and tertiles of fibrinogen (hazard ratio, 3.73; 2.19 to 1.00), factor VII (hazard ratio, 1.86; 1.35 to 1.00), and factor VIII (2.97; 1.70 to 1.00), respectively, but not for antithrombin-III. After adjusting for confounding and known risk factors, fibrinogen independently predicted IS events. A 72% increase (hazard ratio,

ObjectiveTo investigate whether gallstone disease (GD) increases the risk of developing cardiovascular disease (CVD) in a large population-based cohort.MethodsA study population including 6,981 patients with GD was identified from The Taiwan National Health Insurance Research Database between 2004 and 2005. GD patients were defined as patients with principal discharge diagnoses of cholelithiasis using the ICD-9-CM code 574. 27,924 patients without GD were randomly selected and matched for age and gender. All patients were followed for 6 years or until diagnosis for CVD. Cox proportional hazards regression model was used to assess the risk of developing CVD with adjustment for age, gender and co-morbid conditions.ResultsDuring the six years follow-up period, 935 patients with GD and 2,758 patients without GD developed CVD. Patients with GD had an elevated risk of CVD (HR, 1.32; 95% CI, 1.22-1.43) when compared with those without GD. Similar relationship was observed when CVD was categorized i.e. stroke (HR, 1.15; 95% CI, 1.01-1.32), coronary heart disease (HR, 1.42; 95% CI, 1.28-1.58) and heart failure (HR, 1.31; 95% CI, 1.00-1.73). When GD was classified according to the level of severity, using patients without GD as reference, the risks of CVD were elevated in patients with non-severe GD (HR, 1.34; 95% CI, 1.24-1.46) as well as those with severe GD (HR, 1.20, 95% CI, 1.02-1.40), after adjusting for age, gender and comorbidities. In age-stratified analysis, patients aged 18-40 years with GD were at higher risk of developing CVD (HR, 1.42; 95% CI, 1.09-1.84) than older GD patients.ConclusionThis study found an increased risk of CVD in patients diagnosed with GD. The excess risk was particularly high in younger GD patients. Prevention of GD could help reduce the risk of developing CVD, and the better effect could be achieved for the younger age groups.

ObjectiveFeatures of cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy ( CADASIL) caused by NOTCH3 mutations vary between ethnicities and regions. In Taiwan, more than 70% of CADASIL patients carry the mutation hot spot of p.R544C. We investigated the prevalence of NOTCH3 p.R544C mutation in stroke patients in Taiwan.MethodsThis prospective, multicenter study recruited acute stroke patients within 10 days of symptom onset. The p.R544C mutation was identified by polymerase chain reaction with confronting two‐pair primers and sequencing. Clinical parameters, vascular risk factors, stroke subtypes, and stroke outcomes were analyzed.ResultsOf the 1970 stroke patients (mean age 61.1 ± 13.6 years, male 69.5%) included, 1705 (86.5%) had ischemic stroke and 265 (13.5%) had intracerebral hemorrhage. The prevalence of p.R544C in the study population was 2.8% (95% confidence interval [CI] = 2.1–3.5%). The prevalence was highest in patients with small vessel occlusion type of ischemic stroke (5.6%), followed by intracerebral hemorrhage (5.3%), and infarct of undetermined etiology (2.7%), and was low in patients with cardioembolism (0.8%) and large artery atherosclerosis (0.7%). All p.R544C patients with intracerebral hemorrhage were nonlobar hemorrhage. Sibling history of stroke (odds ratio [OR] = 4.50, 95% CI = 1.67–12.14 in ischemic stroke; OR = 6.03, 95% CI = 1.03–35.47 in intracerebral hemorrhage, respectively) and small vessel occlusion (OR, 4.03, 95% CI, 1.26–12.92) were significantly associated with p.R544C.Interpretationp.R544C NOTCH3 mutation is underdiagnosed in stroke patients in Taiwan, especially in those with small vessel occlusion and sibling history of stroke.

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