Global Outcome Assessment Life-long after stroke in young adults initiative-the GOAL initiative: study protocol and rationale of a multicentre retrospective individual patient data meta-analysis.

INTRODUCTION: Worldwide, 2 million patients aged 18-50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients. METHODS AND ANALYSIS: The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18-50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence. ETHICS AND DISSEMINATION: Ethical approval for the GOAL study has already been obtained from the Medical Review Ethics Committee region Arnhem-Nijmegen. Additionally and when necessary, approval will also be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of worldwide differences in risk factors, causes and outcome of young stroke patients.

Intensive blood pressure reduction with intravenous thrombolysis therapy for acute ischaemic stroke (ENCHANTED): an international, randomised, open-label, blinded-endpoint, phase 3 trial.

BACKGROUND: Systolic blood pressure of more than 185 mm Hg is a contraindication to thrombolytic treatment with intravenous alteplase in patients with acute ischaemic stroke, but the target systolic blood pressure for optimal outcome is uncertain. We assessed intensive blood pressure lowering compared with guideline-recommended blood pressure lowering in patients treated with alteplase for acute ischaemic stroke. METHODS: We did an international, partial-factorial, open-label, blinded-endpoint trial of thrombolysis-eligible patients (age ≥18 years) with acute ischaemic stroke and systolic blood pressure 150 mm Hg or more, who were screened at 110 sites in 15 countries. Eligible patients were randomly assigned (1:1, by means of a central, web-based program) within 6 h of stroke onset to receive intensive (target systolic blood pressure 130-140 mm Hg within 1 h) or guideline (target systolic blood pressure <180 mm Hg) blood pressure lowering treatment over 72 h. The primary outcome was functional status at 90 days measured by shift in modified Rankin scale scores, analysed with unadjusted ordinal logistic regression. The key safety outcome was any intracranial haemorrhage. Primary and safety outcome assessments were done in a blinded manner. Analyses were done on intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01422616. FINDINGS: Between March 3, 2012, and April 30, 2018, 2227 patients were randomly allocated to treatment groups. After exclusion of 31 patients because of missing consent or mistaken or duplicate randomisation, 2196 alteplase-eligible patients with acute ischaemic stroke were included: 1081 in the intensive group and 1115 in the guideline group, with 1466 (67·4%) administered a standard dose among the 2175 actually given intravenous alteplase. Median time from stroke onset to randomisation was 3·3 h (IQR 2·6-4·1). Mean systolic blood pressure over 24 h was 144·3 mm Hg (SD 10·2) in the intensive group and 149·8 mm Hg (12·0) in the guideline group (p<0·0001). Primary outcome data were available for 1072 patients in the intensive group and 1108 in the guideline group. Functional status (mRS score distribution) at 90 days did not differ between groups (unadjusted odds ratio [OR] 1·01, 95% CI 0·87-1·17, p=0·8702). Fewer patients in the intensive group (160 [14·8%] of 1081) than in the guideline group (209 [18·7%] of 1115) had any intracranial haemorrhage (OR 0·75, 0·60-0·94, p=0·0137). The number of patients with any serious adverse event did not differ significantly between the intensive group (210 [19·4%] of 1081) and the guideline group (245 [22·0%] of 1115; OR 0·86, 0·70-1·05, p=0·1412). There was no evidence of an interaction of intensive blood pressure lowering with dose (low vs standard) of alteplase with regard to the primary outcome. INTERPRETATION: Although intensive blood pressure lowering is safe, the observed reduction in intracranial haemorrhage did not lead to improved clinical outcome compared with guideline treatment. These results might not support a major shift towards this treatment being applied in those receiving alteplase for mild-to-moderate acute ischaemic stroke. Further research is required to define the underlying mechanisms of benefit and harm resulting from early intensive blood pressure lowering in this patient group. FUNDING: National Health and Medical Research Council of Australia; UK Stroke Association; Ministry of Health and the National Council for Scientific and Technological Development of Brazil; Ministry for Health, Welfare, and Family Affairs of South Korea; Takeda.

Regional variation in acute stroke care organisation.

BACKGROUND: Few studies have assessed regional variation in the organisation of stroke services, particularly health care resourcing, presence of protocols and discharge planning. Our aim was to compare stroke care organisation within middle- (MIC) and high-income country (HIC) hospitals participating in the Head Position in Stroke Trial (HeadPoST). METHODS: HeadPoST is an on-going international multicenter crossover cluster-randomized trial of 'sitting-up' versus 'lying-flat' head positioning in acute stroke. As part of the start-up phase, one stroke care organisation questionnaire was completed at each hospital. The World Bank gross national income per capita criteria were used for classification. RESULTS: 94 hospitals from 9 countries completed the questionnaire, 51 corresponding to MIC and 43 to HIC. Most participating hospitals had a dedicated stroke care unit/ward, with access to diagnostic services and expert stroke physicians, and offering intravenous thrombolysis. There was no difference for the presence of a dedicated multidisciplinary stroke team, although greater access to a broad spectrum of rehabilitation therapists in HIC compared to MIC hospitals was observed. Significantly more patients arrived within a 4-h window of symptoms onset in HIC hospitals (41 vs. 13%; P<0.001), and a significantly higher proportion of acute ischemic stroke patients received intravenous thrombolysis (10 vs. 5%; P=0.002) compared to MIC hospitals. CONCLUSIONS: Although all hospitals provided advanced care for people with stroke, differences were found in stroke care organisation and treatment. Future multilevel analyses aims to determine the influence of specific organisational factors on patient outcomes.

Initial blood pressure is associated with stroke severity and is predictive of admission cost and one-year outcome in different stroke subtypes: a SRICHS registry study.

BACKGROUND: To investigate if initial blood pressure (BP) on admission is associated with stroke severity and predictive of admission costs and one-year-outcome in acute ischemic (IS) and hemorrhagic stroke (HS). METHODS: This is a single-center retrospective cohort study. Stroke patients admitted within 3 days after onset between January 1st and December 31st in 2009 were recruited. The initial BP on admission was subdivided into high (systolic BP ≥ 211 mmHg or diastolic BP ≥ 111 mmHg), medium (systolic BP 111-210 mmHg or diastolic BP 71-110 mmHg), and low (systolic BP ≤ 110 mmHg or diastolic BP ≤ 70 mmHg) groups and further subgrouped with 25 mmHg difference in systole and 10 mmHg difference in diastole for the correlation analysis with demographics, admission cost and one-year modified Rankin scale (mRS). RESULTS: In 1173 IS patients (mean age: 67.8 ± 12.8 years old, 61.4% male), low diastolic BP group had higher frequency of heart disease (p =0.001), dehydration (p =0.03) and lower hemoglobin level (p <0.001). The extremely high and low systolic BP subgroups had worse National Institutes of Health Stroke Scale (NIHSS) score (p =0.03), higher admission cost (p <0.001), and worse one-year mRS (p =0.03), while extremely high and low diastolic BP subgroups had higher admission cost (p <0.01). In 282 HS patients (mean age: 62.4 ± 15.4 years old, 60.6% male), both low systolic and diastolic BP groups had lower hemoglobin level (systole: p =0.05; diastole: p <0.001). The extremely high and low BP subgroups had worse NIHSS score (p =0.01 and p <0.001, respectively), worse one-year mRS (p =0.002 and p =0.001, respectively), and higher admission cost (diastole: p <0.002). CONCLUSIONS: Stroke patients with extremely high and low BP on admission have not only worse stroke severity but also higher admission cost and/or worse one-year outcome. In those patients with low BP, low admission hemoglobin might be a contributing factor.

Readmission, mortality, and first-year medical costs after stroke.

BACKGROUND: Stroke is the leading cause of adult disability and mortality in Taiwan, resulting in a tremendous burden on the healthcare system. The purpose of this study was to characterize disease burden by evaluating readmissions, mortality, and medical cost during the first year after acute stroke under the National Health Insurance (NHI) program. METHODS: This retrospective cohort study extracted information about patients hospitalized with acute stroke from claims data of 200,000 randomly sampled NHI enrollees in Taiwan, with a 1-year follow-up duration. The incidence of the first-year adverse events (AEs) indicated by readmissions or mortality, and the amount of the first-year medical cost (FYMC) were assessed with predictive factors explored. Additionally, we also estimated the cost per life and life-year saved. RESULTS: There were 2368 first-ever stroke patients in our study, including those with subarachnoid hemorrhage (SAH) 3.3%, intracerebral hemorrhage (ICH) 17.9%, ischemic stroke (IS) 49.8%, and transient ischemic attack/other ill-defined cerebrovascular diseases (TIA/unspecified) 29.0%; each stroke type was identified with an all-cause AE of 59.0%, 63.0%, 48.6%, and 46.8%, respectively. Readmissions were mainly because of acute recurrent stroke or the late effects of previous stroke, respiratory disease/infections, heart/circulatory disease, and diseases of the digestive system. Advanced age, hemorrhagic stroke type, respiratory distress/infections, and greater comorbidities were predictive of increased AE risk. Admission to neurology/rehabilitation wards, undertaking neurosurgery, or use of inpatient/outpatient rehabilitation was less likely to incur AEs. Initial hospitalization, readmission, and ambulatory care constituted 44%, 29%, and 27%, respectively, of FYMC with the initial length of stay being the most reliable predictor. The FYMCs were NT $217,959, $246,358, $168,003, and $122,084 for SAH, ICH, IS, and TIA/unspecified, respectively. The cost per life saved were estimated to be NT $435,919, $384,028, $196,281, and $138,888, whereas cost per life-year saved were estimated to be NT$43,926, $48,019, $97,830, and $188,770 for SAH, ICH, IS, and TIA/unspecified, respectively. CONCLUSION: Half of the patients encountered readmission or death during the first year after stroke. Patients with advanced age, more complications, or comorbidities during initial stay tended to be highly vulnerable to AE occurrence, whereas TIA/unspecified stroke carried no less risk for AEs. FYMC or estimated cost per life saved for IS or TIA/unspecified was lower relative to SAH or ICH; however, their estimated cost per life-year saved became higher because of reduced life expectancy.

The impact factors on the cost and length of stay among acute ischemic stroke.

BACKGROUND: Understanding hospital costs and length of stay (LOS) can optimize the in-hospital management of acute stroke. We investigated cost and LOS in first-ever and recurrent stroke patients in Taiwan. METHODS: Data were examined in patients at Chang Gung Memorial Hospital in Chiayi County of Taiwan from April 1, 2008, to March 31, 2010 [corrected]. Predictors of hospital cost and LOS in these patients were studied. RESULTS: The study included 1021 patients with 1084 stroke episodes. Mean age was 68.1 ± 10.8 years (range: 32-93). The average cost was NTD$45,709.30 ± NTD$66,697.40 (US$1408.70 ± US$2084.30; US$1 = NTD$32) and average LOS was 13.9 ± 14.1 days (range: 1-129). After multivariate regression analysis, the significant predictive factors for cost were LOS, smoking, and medication for secondary prevention. The significant predictive factors for LOS were diabetes mellitus, atrial fibrillation, recurrence, and stroke subtype. CONCLUSIONS: Age 65 and over, atrial fibrillation, stroke treatment, and subtypes were the significant predictive factors affecting hospital costs and LOS. Compared to other countries, Taiwan spent the least while Canada had the highest expense. The United States had the shortest LOS (6 days) in contrast to Canada with the longest LOS (34-47 days). Regarding mean daily cost of stroke, the United States had the highest cost per day while China spent the least.

Cost-effectiveness analysis of stroke management under a universal health insurance system.

OBJECTIVE: Cost-effectiveness analysis (CEA) of stroke management was evaluated in three care models: Neurology/Rehabilitation wards (NW), Neurosurgery wards (NS), and General/miscellaneous wards (GW) under a universal health insurance system. METHODS: From 1997 to 2002, subjects with first-ever acute stroke were sampled from claims data of a nationally representative cohort in Taiwan, categorized as hemorrhage stroke (HS) including subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH); or, ischemic stroke (IS), including cerebral infarction (CI), transient ischemic attack/ unspecified stroke (TIA/unspecified); with mild-moderate and severe severity. All-cause readmissions or mortality (AE) and direct medical cost during first-year (FYMC) after stroke were explored. CEA was performed by incremental cost-effectiveness ratios. RESULTS: 2368 first-ever stroke subjects including SAH 3.3%, ICH 17.9%, CI 49.8%, and TIA/unspecified 29.0% were identified with AE 59.0%, 63.0%, 48.6%, 46.8%, respectively. There were 50.8%, 13.5%, 35.6% of stroke patients served by NW, NS and GW with AE 44.9%, 60.6%, 56.0%, and medical costs of US$ 5,031, US$ 8,235, US$ 4,350, respectively. NW was cost-effective for both mild-moderate and severe IS. NS was the dominant care model in mild-moderate HS, while NW appeared to be a cost-minimization model for severe HS. CONCLUSIONS: TIA/unspecified stroke carried substantial risk of AE. NS performed better in serving mild-moderate HS, whereas NW was the optimal care model in management of IS.

Association of nucleophosmin/B23 with bladder cancer recurrence based on immunohistochemical assessment in clinical samples.

AIM: To investigate the possible correlation of nucleophosmin/B23 expression with bladder carcinoma recurrence. METHODS: Surgically-resected bladder tumors staged pTa to pT4 were examined for nucleophosmin/B23 expression by immuno-histochemistry. The study group consisted of 132 consecutive patients surgically treated at Chang Gung Memorial Hospital between December 1998 and November 1999. The mean follow up was 72 months (range: 48-84 months). RESULTS: Nuclear nucleophosmin/B23 staining was detected in 96% of advanced stage and poorly-differentiated tumors. Higher nucleophosmin/B23 levels were linked to more advanced tumor stages, grades, poor prognosis, and likelihood of recurrence (P<0.05). The Cox multivariate analysis indicated the nucleophosmin/B23 expression as an independent indicator for tumor recurrence (P=0.009). CONCLUSION: The results suggest that nucleophosmin/B23 is a favorable prognostic indicator for bladder cancer. Nucleophosmin/B23 could be a useful molecular tumor marker for predicting bladder cancer recurrence.