ORCID Profile
0000-0001-6557-6412
Current Organisations
Université de Sherbrooke
,
University of Helsinki
,
Helsinki University Central Hospital
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Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.JSTROKECEREBROVASDIS.2015.12.016
Abstract: There is increasing interest in the use of administrative data (incorporating comorbidity index) and stroke severity score to predict ischemic stroke mortality. The aim of this study was to determine the optimal timing for the collection of stroke severity data and the minimum clinical dataset to be included in models of stroke mortality. To address these issues, we chose the Virtual International Stroke Trials Archive (VISTA), which contains National Institutes of Health Stroke Scale (NIHSS) on admission and at 24 hours, as well as outcome at 90 days. VISTA was searched for patients who had baseline and 24-hour NIHSS. Improvement in regression models was performed by the net reclassification improvement (NRI) method. The clinical data among 5206 patients were mean age, 69 ± 13 comorbidity index, 3.3 ± .9 median NIHSS at baseline, 12 (interquartile range [IQR] 8-17) NIHSS at 24 hours, 9 (IQR 8-15) and death at 90 days in 15%. The baseline model consists of age, gender, and comorbidity index. Adding the baseline NIHSS to model 1 improved the NRI by 0.671 (95% confidence interval [CI] 0.595-0.747) [or 67.1% correct reclassification between model 1 and model 2]. Adding the 24 hour NIHSS term to model 1 (model 3) improved the NRI by 0.929 (95% CI 0.857-1.000) for model 3 versus model 1. Adding the variable thrombolysis to model 3 (model 4) improve NRI by 0.1 (95% CI 0.023-0.178) [model 4 versus model 3]. The optimal model for the prediction of mortality was achieved by adding the 24-hour NIHSS and thrombolysis to the baseline model.
Publisher: Oxford University Press (OUP)
Date: 09-2002
Abstract: The effectiveness of organized inpatient (stroke unit) care has been demonstrated in systematic reviews of clinical trials. However, the key components of stroke unit care are poorly understood. We conducted a survey of recent trials (published 1985-2000) of a stroke unit/ward which had demonstrated a beneficial effect consistent with the stroke unit systematic review. We identified 11 eligible stroke unit trials of which the majority described similar approaches to i) assessment procedures (medical, nursing and therapy assessments), ii) early management policies (e.g. early mobilization avoidance of urinary catheterization treatment of hypoxia, hyperglycaemia and suspected infection), iii) ongoing rehabilitation policies (e.g. co-ordinated multidisciplinary team care, early assessment for discharge). This survey provides a description of stroke unit care which can serve as a benchmark for general stroke patient care and future clinical research.
Publisher: Wiley
Date: 06-09-2010
Publisher: S. Karger AG
Date: 2002
DOI: 10.1159/000065683
Abstract: i Background: /i Trafermin (basic fibroblast growth factor) has been shown to reduce infarct volume in acute ischemic stroke models, and to promote functional recovery and new synapse formation when given to animals with completed cerebral infarction. A previous study in acute stroke patients suggested that trafermin was safe and well tolerated when given over a 3-hour period over a wide dose range. i Methods and Results: /i Double-blind, parallel group, placebo-controlled trial of a single 24-hour intravenous infusion of trafermin. Patients having onset of stroke symptoms within 6 h and a baseline score of ≧7 on the NIH Stroke Scale (≧2 motor) were randomized to receive 5 or 10 mg of trafermin or placebo intravenously infused over 24 h. The primary efficacy outcome was a categorized combination of the Barthel and Rankin scales assessed at 90 days. A total of 286 patients had been enrolled at 55 sites in 11 countries when the sponsor directed that enrollment be stopped because an interim analysis of efficacy data predicted too small a chance of demonstrating a statistically significant benefit after recruitment of the planned 900 patients. The 5-mg group showed a slight but nonsignificant advantage over placebo (OR 1.2, 95% CI 0.72–2.00, p = 0.48) the 10-mg group showed a nonsignificant disadvantage (OR 0.74, 95% CI 0.44–1.22, p = 0.24). Mortality rates at 90 days were 17% in the 5-mg group, 24% in the 10-mg group and 18% in the placebo group. Treatment with trafermin was associated with an increased leukocytosis and a decrease in blood pressure: mean decrease in systolic blood pressure from baseline was 19 mm Hg in the 5-mg group, 22 mm Hg in the 10-mg group and 8 mm Hg in the placebo group. In a post hoc subgroup analysis, patients in the 5-mg group treated more than 5 h after the onset of symptoms showed an apparent advantage over placebo (OR 2.1, 95% CI 1.00–4.41, p = 0.044 after age adjustment: OR 1.9, 95% CI 0.91–4.13, p = 0.08). i Conclusions: /i With the proper treatment regimen, trafermin can likely be given safely to stroke patients. The 5-mg dose showed a trend toward a treatment advantage. The ideal time window for this agent may exceed 5 h. This may open new avenues for acute stroke therapy, aiming at enhancing recovery mechanisms rather than immediate neuroprotection.
Publisher: SAGE Publications
Date: 10-11-2013
DOI: 10.1111/IJS.12178
Abstract: Clinical deficits from stroke are erse, prompting measurement in trials by a range of outcome scales. Statistical and clinical advantage can be gained by combining scales into a global outcome provided combinations are chosen with limited correlations. We aimed to clarify the interdependence of outcome scales by systematic review of published data and by novel analysis of data from completed acute trials. We systematically searched ScienceDirect and PubMed to summarize published data on correlations between stroke outcome scales. We generated new data on correlations among salient scales at 90 days poststroke in patients from the Virtual International Stroke Trials Archive (VISTA). We calculated Pearson and Spearman-Rank correlation coefficients for continuous and ordinal measures, respectively. We also assessed partial correlations, adjusted for baseline National Institute of Health Stroke Scale (NIHSS), and age. Published estimates of interdependence were limited to small single-trial cohorts and gave ergent results. From the more extensive VISTA dataset, we found that the modified Rankin Scale at 90 days poststroke explained 80.8% of the National Institute of Health Stroke Scale at 90 days poststroke and 86·5% of the European Stroke Scale. National Institute of Health Stroke Scale explained 75.9% of the Barthel Index and 81·2% of the Scandinavian Stroke Scale. After adjustment, modified Rankin Scale explained 56.6% of National Institute of Health Stroke Scale, 75.2% of Barthel Index. National Institute of Health Stroke Scale explained 60.2% of Barthel Index. Correlations and partial correlations among stroke outcome scales in trial datasets are higher than previously reported. The new estimates are more reliable for trial planning due to the s le size and ersity.
Publisher: SAGE Publications
Date: 06-07-2015
DOI: 10.1111/IJS.12551
Abstract: The 2015 update of the Canadian Stroke Best Practice Recommendations Hyperacute Stroke Care guideline highlights key elements involved in the initial assessment, stabilization, and treatment of patients with transient ischemic attack (TIA), ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and acute venous sinus thrombosis. The most notable change in this 5th edition is the addition of new recommendations for the use of endovascular therapy for patients with acute ischemic stroke and proximal intracranial arterial occlusion. This includes an overview of the infrastructure and resources required for stroke centers that will provide endovascular therapy as well as regional structures needed to ensure that all patients with acute ischemic stroke that are eligible for endovascular therapy will be able to access this newly approved therapy recommendations for hyperacute brain and enhanced vascular imaging using computed tomography angiography and computed tomography perfusion patient selection criteria based on the five trials of endovascular therapy published in early 2015, and performance metric targets for important time-points involved in endovascular therapy, including computed tomography-to-groin puncture and computed tomography-to-reperfusion times. Other updates in this guideline include recommendations for improved time efficiencies for all aspects of hyperacute stroke care with a movement toward a new median target door-to-needle time of 30 min, with the 90th percentile being 60 min. A stronger emphasis is placed on increasing public awareness of stroke with the recent launch of the Heart and Stroke Foundation of Canada FAST signs of stroke c aign reinforcing the public need to seek immediate medical attention by calling 911 further engagement of paramedics in the prehospital phase with prehospital notification to the receiving emergency department, as well as the stroke team, including neuroradiology updates to the triage and same-day assessment of patients with transient ischemic attack updates to blood pressure recommendations for the hyperacute phase of care for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. The goal of these recommendations and supporting materials is to improve efficiencies and minimize the absolute time lapse between stroke symptom onset and reperfusion therapy, which in turn leads to better outcomes and potentially shorter recovery times.
Publisher: Public Library of Science (PLoS)
Date: 09-02-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2014
DOI: 10.1161/STROKEAHA.113.002910
Abstract: Stroke thrombolysis is highly time-critical, but data on long-term effects of small reductions in treatment delays have not been available. Our objective was to quantify patient lifetime benefits gained from faster treatment. Observational prospective data of consecutive stroke patients treated with intravenous thrombolysis in Australian and Finnish centers (1998–2011 n=2258) provided distributions of age, sex, stroke severity, onset-to-treatment times, and 3-month modified Rankin Scale in daily clinical practice. Treatment effects derived from a pooled analysis of thrombolysis trials were used to model the shift in 3-month modified Rankin Scale distributions with reducing treatment delays, from which we derived the expected lifetime and level of long-term disability with faster treatment. Each minute of onset-to-treatment time saved granted on average 1.8 days of extra healthy life (95% prediction interval, 0.9–2.7). Benefit was observed in all groups: each minute provided 0.6 day in old severe (age, 80 years National Institutes of Health Stroke Scale [NIHSS] score, 20) patients, 0.9 day in old mild (age, 80 years NIHSS score, 4) patients, 2.7 days in young mild (age, 50 years NIHSS score, 4) patients, and 3.5 days in young severe (age, 50 years NIHSS score, 20) patients. Women gained slightly more than men over their longer lifetimes. In the whole cohort, each 15 minute decrease in treatment delay provided an average equivalent of 1 month of additional disability-free life. Realistically achievable small reductions in stroke thrombolysis delays would result in significant and robust average health benefits over patients’ lifetimes. The awareness of concrete importance of speed could promote practice change.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2015
DOI: 10.1161/STROKEAHA.114.006837
Abstract: National Institutes of Health Stroke Scale (NIHSS) item profiles that were recently proposed may prove useful both clinically and for research studies. We aimed to validate the NIHSS item profiles in an acute cohort. We conducted a retrospective analysis on pooled data from randomized clinical trials. We applied the latent class analysis probabilities of profile membership developed from the derivation study to obtain symptom grouping, a -NIHSS item profiles. We implemented an independent latent class analysis to derive secondary symptom grouping, b -NIHSS item profiles. Validation was performed by assessing the associations with outcomes and evaluating both sets of NIHSS item profiles’ discrimination and calibration to the data. The outcomes evaluated included modified Rankin Scale (mRS using the full distribution and dichotomized, mRS, 0–1) at day 90 and mortality by 90 days. We identified 10 271 patients. Ordinal analysis of mRS confirmed increased odds of better outcome across the profiles in a stepwise manner, adjusted for age and thrombolysis treatment, for each set of NIHSS item profiles. Similar patterns were observed for mRS 0 to 1, and inverse patterns were seen for mortality. The c -statistics of a -NIHSS and b -NIHSS item profiles for mRS 0 to 1 were similar at 0.71 (95% confidence interval, 0.70–0.72) and for mortality, 0.74 (0.73–0.75) and 0.75 (0.73–0.76), respectively. Calibration was good. These NIHSS item profiles identified using latent class analysis offer a reliable approach to capture the true response patterns that are associated with functional and outcome and mortality post stroke. This approach has the potential to enhance the clinical value of the overall NIHSS score.
Publisher: SAGE Publications
Date: 22-10-2013
DOI: 10.1111/IJS.12131
Abstract: Clinical trials for acute ischemic stroke treatment require large numbers of participants and are expensive to conduct. Methods that enhance statistical power are therefore desirable. We explored whether this can be achieved by a measure incorporating both early and late measures of outcome (e.g. seven-day NIH Stroke Scale combined with 90-day modified Rankin scale). We analyzed sensitivity to treatment effect, using proportional odds logistic regression for ordinal scales and generalized estimating equation method for global outcomes, with all analyses adjusted for baseline severity and age. We ran simulations to assess relations between s le size and power for ordinal scales and corresponding global outcomes. We used R version 2·12·1 (R Development Core Team. R Foundation for Statistical Computing, Vienna, Austria) for simulations and SAS 9·2 (SAS Institute Inc., Cary, NC, USA) for all other analyses. Each scale considered for combination was sensitive to treatment effect in isolation. The mRS90 and NIHSS90 had adjusted odds ratio of 1·56 and 1·62, respectively. Adjusted odds ratio for global outcomes of the combination of mRS90 with NIHSS7 and NIHSS90 with NIHSS7 were 1·69 and 1·73, respectively. The smallest s le sizes required to generate statistical power ≥80% for mRS90, NIHSS7, and global outcomes of mRS90 and NIHSS7 combined and NIHSS90 and NIHSS7 combined were 500, 490, 400, and 380, respectively. When data concerning both early and late outcomes are combined into a global measure, there is increased sensitivity to treatment effect compared with solitary ordinal scales. This delivers a 20% reduction in required s le size at 80% power. Combining early with late outcomes merits further consideration.
Publisher: Elsevier BV
Date: 07-2018
Publisher: Elsevier BV
Date: 10-1998
DOI: 10.1016/S0140-6736(98)08020-9
Abstract: Thrombolysis for acute ischaemic stroke has been investigated in several clinical trials, with variable results. We have assessed the safety and efficacy of intravenous thrombolysis with alteplase (0.9 mg/kg bodyweight) within 6 h of stroke onset. This non-angiographic, randomised, double-blind, trial enrolled 800 patients in Europe, Australia, and New Zealand. Computed tomography was used to exclude patients with signs of major infarction. Alteplase (n=409) and placebo (n=391) were randomly assigned with stratification for time since symptom onset (0-3 h or 3-6 h). The primary endpoint was the modified Rankin scale (mRS) at 90 days, dichotomised for favourable (score 0-1) and unfavourable (score 2-6) outcome. Analyses were by intention to treat. 165 (40.3%) alteplase-group patients and 143 (36.6%) placebo-group patients had favourable mRS outcomes (absolute difference 3.7%, p=0.277). In a posthoc analysis of mRS scores dichotomised for death or dependency, 222 (54.3%) alteplase-group and 180 (46.0%) placebo-group patients had favourable outcomes (score 0-2 absolute difference 8.3%, p=0.024). Treatment differences were similar whether patients were treated within 3 h or 3-6 h. 85 (10.6%) patients died, with no difference between treatment groups at day 90+/-14 days (43 alteplase, 42 placebo). Symptomatic intracranial haemorrhage occurred in 36 (8.8%) alteplase-group patients and 13 (3.4%) placebo-group patients. The results do not confirm a statistical benefit for alteplase. However, we believe the trend towards efficacy should be interpreted in the light of evidence from previous trials. Despite the increased risk of intracranial haemorrhage, thrombolysis with alteplase at a dose of 0.9 mg/kg in selected patients may lead to a clinically relevant improvement in outcome.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2013
DOI: 10.1161/STROKEAHA.113.001564
Abstract: Patients with any type of stroke managed in organized inpatient (stroke unit) care are more likely to survive, return home, and regain independence. However, it is uncertain whether these benefits apply equally to patients with intracerebral hemorrhage and ischemic stroke. We conducted a secondary analysis of a systematic review of controlled clinical trials comparing stroke unit care with general ward care, including only trials published after 1990 that could separately report outcomes for patients with intracerebral hemorrhage and ischemic stroke. We performed random-effects meta-analyses and tested for subgroup interactions by stroke type. We identified 13 trials (3570 patients) of modern stroke unit care that recruited patients with intracerebral hemorrhage and ischemic stroke, of which 8 trials provided data on 2657 patients. Stroke unit care reduced death or dependency (risk ratio [RR], 0.81 95% confidence interval [CI], 0.471–0.92 P =0.0009 I 2 =60%) with no difference in benefits for patients with intracerebral hemorrhage (RR, 0.79 95% CI, 0.61–1.00) than patients with ischemic stroke (RR, 0.82 95% CI, 0.70–0.97 P interaction =0.77). Stroke unit care reduced death (RR, 0.79 95% CI, 0.64–0.97 P =0.02 I 2 =49%) to a greater extent for patients with intracerebral hemorrhage (RR, 0.73 95% CI, 0.54–0.97) than patients with ischemic stroke (RR, 0.82 95%, CI 0.61–1.09), but this difference was not statistically significant ( P interaction =0.58). Patients with intracerebral hemorrhage seem to benefit at least as much as patients with ischemic stroke from organized inpatient (stroke unit) care.
Publisher: Elsevier BV
Date: 11-2014
Publisher: SAGE Publications
Date: 03-11-2010
DOI: 10.1111/J.1747-4949.2010.00485.X
Abstract: Stroke rehabilitation is a complex intervention. Many factors influence the interaction between the patient and the elements of the intervention. Rehabilitation interventions are aimed at altering different domains of patient outcome including body functions, activity and participation. As a consequence, randomised clinical trials in this area are difficult to design. We developed an archive of stroke rehabilitation trials (VISTA-Rehab) to act as a resource to help trialists model and design future rehabilitation studies. We developed specific eligibility criteria for the entry of stroke rehabilitation trials into the archive. We established a Steering Committee to oversee projects and publications and commenced the recruitment of rehabilitation trials into this resource. As of August 2009, VISTA-Rehab contains data from 23 stroke rehabilitation trials ( patients). Demographic data, including age [median=73, interquartile range (63,79)], gender (male=53%) and initial dependency [median baseline Barthel index score=6, interquartile range ( 9 , 19 )], are available for all patients. Outcome measures include the modified Rankin Scale, Barthel Index, Rivermead Motor Assessment, Fugl-Meyer Assessment, General Health Questionnaire and Nottingham Extended Activities of Daily Living Scale. VISTA-Rehab expands the Virtual International Stroke Trials Archive to include rehabilitation trials. Anonymised data can be used to examine questions specific to stroke rehabilitation and to generate novel hypotheses.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2014
DOI: 10.1161/STROKEAHA.113.004251
Abstract: Severe atherosclerosis in the aortic arch is associated with a high risk of recurrent vascular events, but the optimal antithrombotic strategy is unclear. This prospective randomized controlled, open-labeled trial, with blinded end point evaluation (PROBE design) tested superiority of aspirin 75 to 150 mg/d plus clopidogrel 75 mg/d (A+C) over warfarin therapy (international normalized ratio 2–3) in patients with ischemic stroke, transient ischemic attack, or peripheral embolism with plaque in the thoracic aorta mm and no other identified embolic source. The primary end point included cerebral infarction, myocardial infarction, peripheral embolism, vascular death, or intracranial hemorrhage. Follow-up visits occurred at 1 month and then every 4 months post randomization. The trial was stopped after 349 patients were randomized during a period of 8 years and 3 months. After a median follow-up of 3.4 years, the primary end point occurred in 7.6% (13/172) and 11.3% (20/177) of patients on A+C and on warfarin, respectively (log-rank, P =0.2). The adjusted hazard ratio was 0.76 (95% confidence interval, 0.36–1.61 P =0.5). Major hemorrhages including intracranial hemorrhages occurred in 4 and 6 patients in the A+C and warfarin groups, respectively. Vascular deaths occurred in 0 patients in A+C arm compared with 6 (3.4%) patients in the warfarin arm (log-rank, P =0.013). Time in therapeutic range (67% of the time for international normalized ratio 2–3) analysis by tertiles showed no significant differences across groups. Because of lack of power, this trial was inconclusive and results should be taken as hypothesis generating. URL: www.clinicaltrials.gov . Unique identifier: NCT00235248.
Publisher: SAGE Publications
Date: 12-2009
DOI: 10.1111/J.1747-4949.2009.00348.X
Abstract: Poststroke complications such as pulmonary embolism, deep vein thrombosis and pneumonia can impact outcome by causing deterioration in general health, delaying or preventing rehabilitation. While stroke carries a direct risk of complications, some events may be unrelated to index stroke severity and could confound outcome. We examined whether the presence of complications ‘unrelated’ to index stroke at later time-points could confound outcome, and if this could be minimised through altering study end-points. We analysed 531 placebo-treated patients from the Virtual International Stroke Trials Archive who had experienced an acute ischaemic stroke and at least one poststroke complication during the 90-day follow-up period. We categorised complications into those deemed ‘related’ or ‘unrelated’ to index stroke severity. We examined modified Rankin Scale at 30 and 90 days, stratified by type of complication and assessed the impact of eliminating ‘unrelated’ complications on functional outcome (modified Rankin Scale) at 30 and 90 days using logistic regression (accounting for age and baseline National Institutes of Health Stroke Scale). The majority of complications in the early acute period after index stroke were ‘stroke related’ (30·2%). Patients did not have a better modified Rankin Scale profile at 30 days when compared with 90 days, regardless of the type of complications experienced. The absence of ‘stroke unrelated’ complications was associated with a worse outcome at 30 days [ P = 0·04, adjusted odds ratio for good functional outcome = 0·54, 95% confidence interval (0·3, 0·96)], and had no significant effect on outcome at 90 days. We identified complications, which we deemed not to have occurred as a direct consequence of index stroke, but found that the absence of these events did not beneficially alter outcome at either short-term (30 days) or long-term (90 days) follow-up periods. Our analyses did not support the shortening of trial follow-up periods with the aim of minimising the risk of stroke-unrelated complications.
Publisher: SAGE Publications
Date: 06-07-2010
DOI: 10.1111/J.1747-4949.2010.00442.X
Abstract: The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke. Preliminary work was performed by seven working groups of stroke leaders followed by a synergium (a forum for working synergistically together) with approximately 100 additional participants. The resulting draft document had further input from contributors outside the synergium. Recommendations of the Synergium are: : There is a need to develop: ( 1 ) New systems of working together to break down the prevalent ‘silo’ mentality ( 2 ) New models of vertically integrated basic, clinical, and epidemiological disciplines and ( 3 ) Efficient methods of identifying other relevant areas of science. : ( 1 ) Establish a global chronic disease prevention initiative with stroke as a major focus. ( 2 ) Recognize not only abrupt clinical stroke, but subtle subclinical stroke, the commonest type of cerebrovascular disease, leading to impairments of executive function. ( 3 ) Develop, implement and evaluate a population approach for stroke prevention. ( 4 ) Develop public health communication strategies using traditional and novel (eg, social media/marketing) techniques. : Continue the establishment of stroke centers, stroke units, regional systems of emergency stroke care and telestroke networks. : ( 1 ) Translate best neuroscience, including animal and human studies, into poststroke recovery research and clinical care. ( 2 ) Standardize poststroke rehabilitation based on best evidence. ( 3 ) Develop consensus on, then implementation of, standardized clinical and surrogate assessments. ( 4 ) Carry out rigorous clinical research to advance stroke recovery. :( 1 ) Work toward global unrestricted access to stroke-related information. ( 2 ) Build centralized electronic archives and registries. (large stroke organizations, nongovernmental organizations, governments, patient organizations and industry) to enhance stroke care. by using a ***‘Brain Health’ concept that enables promotion of preventive measures. To accelerate progress in stroke, we must reach beyond the current status scientifically, conceptually, and pragmatically. Advances can be made not only by doing, but ceasing to do. Significant savings in time, money, and effort could result from discontinuing practices driven by unsubstantiated opinion, unproven approaches, and financial gain. Systematic integration of knowledge into programs coupled with careful evaluation can speed the pace of progress.
Publisher: Wiley
Date: 22-04-2019
DOI: 10.1111/PHP.13100
Abstract: Zinc pyrithione is ubiquitous in commercial products particularly antidandruff sh oos. For the efficacy of zinc pyrithione therapeutic cleansers to be assessed accurately, the distribution of particles on the scalp needs to be visualized. Currently, no technique is available which provides the chemical specificity and sensitivity required. Here, we report application of fluorescence-lifetime imaging microscopy (FLIM) for high-contrast mapping of zinc pyrithione distribution on the scalp. Characterization of the zinc pyrithione emission by using both one-photon excitation at five specific wavelengths and two-photon excitation in the range of 740-820 nm revealed its FLIM fingerprint-a characteristic short average time-weighted emission lifetime of Τ
Publisher: Wiley
Date: 25-08-2014
DOI: 10.1111/ENE.12548
Abstract: There are concerns that systemic thrombolysis might not achieve clinically important outcome amongst chronic heart failure (CHF) patients with acute ischaemic stroke. Our aim was to investigate the relevance of CHF on the outcome of acute stroke patients who received thrombolysis. A non-randomized cohort analysis was conducted using data obtained from the Virtual International Stroke Trials Archive. The association of outcome amongst CHF patients with thrombolysis treatment was described using the modified Rankin scale (mRS) distribution at day 90, stratified by the presence of atrial fibrillation. Dichotomized outcomes were considered as a secondary end-point. 5677 patients were identified, of whom 2366 (41.7%) received thombolysis. Five hundred and three (8.9%) patients had CHF, of whom 209 (41.6%) received thrombolysis. The presence of CHF was associated with a negative impact on overall stroke outcome [odds ratio (OR) 0.73 (95% confidence interval (CI) 0.62-0.87), P < 0.001]. However, thrombolysis treatment was associated with favourable functional outcome using ordinal mRS, irrespective of CHF status, after adjustment for age and baseline National Institutes of Health Stroke Scale [OR 1.44 (95% CI 1.04-2.01, P = 0.029) for CHF patients versus OR 1.50 (95% CI 1.36-1.66, P < 0.001) for non-CHF patients]. CHF patients had higher mortality at day 90 than non-CHF patients. There was no significant difference for recurrent stroke or symptomatic intracerebral haemorrhage within 7 days of the initial stroke between CHF and thrombolysis groups. Chronic heart failure was associated with a worse outcome with or without thrombolysis. However, acute stroke patients who received thrombolysis had more favourable outcome regardless of CHF status, compared with their untreated peers. Our findings should reassure clinicians considering systemic thrombolysis treatment in hyperacute ischaemic stroke patients with CHF.
Publisher: Elsevier BV
Date: 07-2019
Publisher: S. Karger AG
Date: 16-12-2015
DOI: 10.1159/000442532
Abstract: b i Background: /i /b This study aimed at identifying the determinants and prognostic significance of a sedimentation level (fluid-blood level) in the hematoma among patients with acute intracerebral hemorrhage (ICH) who participated in the main Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). b i Methods: /i /b Post-hoc analysis of the INTERACT2 dataset, a randomized controlled trial of patients with acute ICH with elevated systolic blood pressure (SBP), randomly assigned to intensive (target SBP mm Hg) or guideline-based ( mm Hg) BP management. Patients with a sedimentation level at baseline assessment on CT, and modified Rankin Scale score at 90-day, were included in these analyses. Factors associated with a sedimentation level and its significance in relation to 90-day clinical outcomes were assessed in univariable and multivariable logistic regression models. b i Results: /i /b Of 2,065 participants, 19 (1%) had sedimentation level on baseline CT, which was independently associated with warfarin use (p = 0.006) and lobar ICH (p = 0.025). Sedimentation level was also associated with death or major disability at 90-day in both crude (84 vs. 53% p = 0.014) and multivariable analyses adjusted for age, gender, Chinese region, warfarin use, baseline National Institutes of Health Stroke Scale score, onset to CT time, volume and location of ICH, intraventricular extension, and randomized intensive BP lowering (OR 3.94, 95% CI 1.01-15.37 p = 0.049). b i Conclusions: /i /b The presence of hematoma sedimentation level on baseline CT is associated with warfarin use and lobar location of ICH, and predicts a worse outcome. Although uncommon, sedimentation level is an easily detectable prognostic factor in acute ICH.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2016
DOI: 10.1161/STROKEAHA.116.013644
Abstract: Thrombolytic therapy with intravenous alteplase within 4.5 hours of ischemic stroke onset increases the overall likelihood of an excellent outcome (no, or nondisabling, symptoms). Any improvement in functional outcome distribution has value, and herein we provide an assessment of the effect of alteplase on the distribution of the functional level by treatment delay, age, and stroke severity. Prespecified pooled analysis of 6756 patients from 9 randomized trials comparing alteplase versus placebo/open control. Ordinal logistic regression models assessed treatment differences after adjustment for treatment delay, age, stroke severity, and relevant interaction term(s). Treatment with alteplase was beneficial for a delay in treatment extending to 4.5 hours after stroke onset, with a greater benefit with earlier treatment. Neither age nor stroke severity significantly influenced the slope of the relationship between benefit and time to treatment initiation. For the observed case mix of patients treated within 4.5 hours of stroke onset (mean 3 hours and 20 minutes), the net absolute benefit from alteplase (ie, the difference between those who would do better if given alteplase and those who would do worse) was 55 patients per 1000 treated (95% confidence interval, 13–91 P =0.004). Treatment with intravenous alteplase initiated within 4.5 hours of stroke onset increases the chance of achieving an improved level of function for all patients across the age spectrum, including the over 80s and across all severities of stroke studied (top versus bottom fifth means: 22 versus 4) the earlier that treatment is initiated, the greater the benefit.
Publisher: SAGE Publications
Date: 22-10-2013
DOI: 10.1111/IJS.12148
Abstract: Benzodiazepines have been proposed both as a neuroprotectant and risk factor for pneumonia in acute stroke. Aims We assessed the impact of benzodiazepine exposure on the modified Rankin scale score distribution at 90 days as well as pneumonia rates among patients registered in a trials archive. We used an age, baseline National Institutes of Health Stroke Score, and thrombolysis-rate adjusted Cochran–Mantel–Haenszel test to test significance ( P) followed by proportional odds logistic regression analysis to estimate the odds ratios for improved modified Rankin scale score, and binary logistic regression to estimate the odds ratio for developing pneumonia. Data were available for 5938 patients, of whom 1800 received benzodiazepines. No association of benzodiazepine use and overall stroke outcome could be found (odds ratio 0·90, 95% confidence interval 0·82–1·00, P = 0·121). Pneumonia occurred in 12·8% of patients treated with benzodiazepines and in 13·6% of the controls (odds ratio 0·99, 95% confidence interval 0·83–1·18, P = 0·904). In this nonrandomized comparison, treatment with benzodiazepines as a concomitant medication had no independent impact on stroke outcome.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 18-01-2008
Abstract: The evolutionary changes that occur over a small number of generations in natural populations often run counter to what is expected on the basis of the heritability of traits and the selective forces acting upon them. In Soay sheep, dark coat color is associated with large size, which is heritable and positively correlated with fitness, yet the frequency of dark sheep has decreased. This unexpected microevolutionary trend is explained by genetic linkage between the causal mutation underlying the color polymorphism and quantitative trait loci with antagonistic effects on size and fitness. As a consequence, homozygous dark sheep are large, but have reduced fitness relative to phenotypically indistinguishable dark heterozygotes and light sheep. This result demonstrates the importance of understanding the genetic basis of fitness variation when making predictions about the microevolutionary consequences of selection.
Publisher: S. Karger AG
Date: 2010
DOI: 10.1159/000315099
Publisher: SAGE Publications
Date: 05-09-2013
DOI: 10.1111/IJS.12123
Abstract: Reliable estimates of intracluster correlation coefficients (ICCs) for specific outcome measures are crucial for s le size calculations of future cluster randomized trials. ICCs indicate the proportion of data variability that is explained by defined levels of clustering. In this manuscript, we present potentially valuable and reliable estimates of ICCs for specific baseline and follow-up data. ICCs were estimated from linear and generalized linear mixed models using maximum likelihood estimation for common measures used in stroke research, including modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), and Barthel Index (BI). Data were available for 11 841 patients with ischemic stroke from 11 randomized trials. After adjusting for age, thrombolysis, and baseline NIHSS, the median ICC for follow-up data, using center as the level of clustering, ranged from 0·007 to 0·041. The ICCs using trial, continent or year of enrollment as level of clustering were distinctly lower. Less than 1% of the variability of mRS, NIHSS, and BI was explained by any of these three cluster levels. This compendium of relevant ICC estimates should assist trial planning. For ex le, the s le size for a cluster trial with 150 patients per center using ordinal analysis of mRS should be inflated by 2·0 due to the ICC of 0·007 whereas the ICC of 0·031 using mRS dichotomized above mRS 0–1, requires inflation by 5·6. The low contribution of trials, year or continent of enrollment to overall variation in outcome offers reassurance that analyses using pooled data from multiple trials in VISTA are unlikely to suffer from bias from these sources.
Publisher: S. Karger AG
Date: 2008
DOI: 10.1159/000131083
Abstract: This article represents the update of the European Stroke Initiative Recommendations for Stroke Management. These guidelines cover both ischaemic stroke and transient ischaemic attacks, which are now considered to be a single entity. The article covers referral and emergency management, Stroke Unit service, diagnostics, primary and secondary prevention, general stroke treatment, specific treatment including acute management, management of complications, and rehabilitation.
Publisher: SAGE Publications
Date: 22-10-2013
DOI: 10.1111/IJS.12162
Abstract: The National Institutes of Neurological Disorders and Stroke and the European Co-operative Acute Stroke III trials enrolled a largely Caucasian population, but the results are often extrapolated onto non-Caucasians. A limited number of nonrandomized studies have proposed that non-Caucasian patients show differential response to tissue plasminogen activator. We examined if non-Caucasian patients of mixed national origin within the Virtual International Stroke Trials Archives neuroprotection trials responded differently to tissue plasminogen activator compared with Caucasians. We matched patients within each race-subtype for age, baseline National Institutes of Health Stroke Scales, and diabetes status, and excluded outliers. We tested for an interaction of race ethnicity with tissue plasminogen activator on predicting outcomes at α = 0·05. We compared 90-day ordinal outcome (modified Rankin Scale primary analysis) and dichotomized outcomes (modified Rankin Scale 0–1 modified Rankin Scale 0–2 survival) within in idual race ethnicity. One thousand nine hundred forty-six thrombolysed patients (125 Blacks, 39 Asians, and 1821 Caucasians) were matched with 1946 non-thrombolysed patients in each race ethnicity group. Postmatching, there were no imbalances in baseline National Institutes of Health Stroke Scales and age between the groups ( P 0·05). The interaction of tissue plasminogen activator with race ethnicity was nonsignificant in ordinal ( P = 0·4) and in dichotomized outcome models ( P 0·05). Ordinal odds for improved outcomes were 1·5 for all patients ( P 0·05). Ordinal odds for Caucasians were 1·5 ( P 0·05) for Blacks, 2·1 ( P 0·05) and for Asians, 1·2 ( P 0·05 1·6 after 1:2 matching with nonthrombolysed, because of small numbers). Dichotomized functional outcomes improved after thrombolysis overall, in Caucasians, in Blacks (modified Rankin Scale 0–2 only), and in Asians (after 1:2 matching P 0·05). Odds for survival were consistent across all groups. These results do not suggest a differential response to tissue plasminogen activator based on race ethnicity. Among Asians, data were particularly sparse, and results should be interpreted with caution.
Publisher: SAGE Publications
Date: 24-11-2017
Abstract: The recommended maximum age and time window for intravenous alteplase treatment of acute ischemic stroke differs between the Europe Union and United States. We compared the effects of alteplase in cohorts defined by the current Europe Union or United States marketing approval labels, and by hypothetical revisions of the labels that would remove the Europe Union upper age limit or extend the United States treatment time window to 4.5 h. We assessed outcomes in an in idual-patient-data meta-analysis of eight randomized trials of intravenous alteplase (0.9 mg/kg) versus control for acute ischemic stroke. Outcomes included: excellent outcome (modified Rankin score 0–1) at 3–6 months, the distribution of modified Rankin score, symptomatic intracerebral hemorrhage, and 90-day mortality. Alteplase increased the odds of modified Rankin score 0–1 among 2449/6136 (40%) patients who met the current European Union label and 3491 (57%) patients who met the age-revised label (odds ratio 1.42, 95% CI 1.21−1.68 and 1.43, 1.23−1.65, respectively), but not in those outside the age-revised label (1.06, 0.90−1.26). By 90 days, there was no increased mortality in the current and age-revised cohorts (hazard ratios 0.98, 95% CI 0.76−1.25 and 1.01, 0.86–1.19, respectively) but mortality remained higher outside the age-revised label (1.19, 0.99–1.42). Similarly, alteplase increased the odds of modified Rankin score 0-1 among 1174/6136 (19%) patients who met the current US approval and 3326 (54%) who met a 4.5-h revised approval (odds ratio 1.55, 1.19−2.01 and 1.37, 1.17−1.59, respectively), but not for those outside the 4.5-h revised approval (1.14, 0.97−1.34). By 90 days, no increased mortality remained for the current and 4.5-h revised label cohorts (hazard ratios 0.99, 0.77−1.26 and 1.02, 0.87–1.20, respectively) but mortality remained higher outside the 4.5-h revised approval (1.17, 0.98–1.41). An age-revised European Union label or 4.5-h-revised United States label would each increase the number of patients deriving net benefit from alteplase by 90 days after acute ischemic stroke, without excess mortality.
Publisher: SAGE Publications
Date: 03-05-2013
DOI: 10.1111/IJS.12040
Abstract: Thrombolysis with intravenous alteplase is both effective and safe when administered to particular types of patient within 4·5 hours of having an ischemic stroke. However, the extent to which effects might vary in different types of patient is uncertain. We describe the protocol for an updated in idual patient data meta-analysis of trials of intravenous alteplase, including results from the recently reported third International Stroke Trial, in which a wide range of patients enrolled up to six-hours after stroke onset were randomized to alteplase vs. control. This protocol will specify the primary outcome for efficacy, specified prior to knowledge of the results from the third International Stroke Trial, as the proportion of patients having a ‘favorable’ stroke outcome, defined by modified Rankin Score 0–1 at final follow-up at three- to six-months. The primary analysis will be to estimate the extent to which the known benefit of alteplase on modified Rankin Score 0–1 diminishes with treatment delay, and the extent to which it is independently modified by age and stroke severity. Key secondary outcomes include effect of alteplase on death within 90 days analyses of modified Rankin Score using ordinal, rather than dichotomous, methods and effects of alteplase on symptomatic intracranial hemorrhage, fatal intracranial hemorrhage, symptomatic ischemic brain edema and early edema, effacement and/or midline shift. This collaborative meta-analysis of in idual participant data from all randomized trials of intravenous alteplase vs. control will demonstrate how the known benefits of alteplase on ischemic stroke outcome vary across different types of patient.
Publisher: Public Library of Science (PLoS)
Date: 11-05-2015
Publisher: SAGE Publications
Date: 02-2008
Publisher: SAGE Publications
Date: 07-01-2013
DOI: 10.1111/J.1747-4949.2012.00943.X
Abstract: Approved use of intravenous alteplase for ischemic stroke offers net benefit. Pooled randomized controlled trial analysis suggests additional patients could benefit but others be harmed with treatment initiated beyond 4·5 h after stroke onset. We proposed prognostic scoring methods to identify a strategy for patient selection. We selected 500 patients treated by intravenous alteplase and 500 controls from Virtual International Stroke Trials Archive, matching modified Rankin score outcomes to those from pooled randomized controlled trial 4·5–6 h data. We ranked patients by prognostic score. We chose limits to optimize our s le for a net treatment benefit significant at P = 0·01 by Cochran–Mantel–Haenszel test and by ordinal regression. For validation, we had these applied to the pooled randomized controlled trial data for 4·5–6 h, testing for net benefit by Cochran–Mantel–Haenszel test, ordinal regression, and also by dichotomized outcomes: modified Rankin score 0–1, mortality and parenchymal hemorrhage type 2 bleeds. All analyses were adjusted for age and National Institutes of Health Stroke Scale. In the training dataset, limits of 56–95 on a prognostic score retained 714 patients in whom there was net benefit significant at P = 0·01. When applied to the 1120 patients in the pooled randomized controlled trial 4·5–6 h dataset, score limits of 56–95 retained 711 patients and gave odds ratio for improved modified Rankin score distribution of 1·13, 95% confidence interval 0·87–1·47, Cochran–Mantel–Haenszel P = 0·89. More patients achieved modified Rankin score 0–1 (odds ratio 1·44, 1·02–2·05, P = 0·04) but mortality and parenchymal hemorrhage type 2 bleeds were increased: odds ratio 1·56, 1·01–2·40, P = 0·04 odds ratio 15·6, 3·7–65·8, P = 0·0002, respectively. Selection of patients between 4·5 and 6 h based on simple clinical measures failed to deliver a population in whom the alteplase effect would be safe and effective.
Publisher: SAGE Publications
Date: 20-01-2012
DOI: 10.1111/J.1747-4949.2011.00735.X
Abstract: Analysis of reliable registry data can direct future research to influence clinical care. Data from the Virtual International Stroke Trials Archive have been used to test hypotheses and inform trial design. We sought to expand Virtual International Stroke Trials Archive into a broader stroke resource with new opportunities for research and international collaboration. Using procedures initially developed for an acute stroke trial archive, we invited trialists to lodge data on rehabilitation, secondary prevention, intracerebral haemorrhage, imaging, and observational stroke studies. We have extended Virtual International Stroke Trials Archive into six subsections: Virtual International Stroke Trials Archive-Acute ( n = 28 190 patients’ data), Virtual International Stroke Trials Archive-Rehab ( n = 10 194), Virtual International Stroke Trials Archive-intracerebral haemorrhage ( n = 1829), Virtual International Stroke Trials Archive-Prevention, Virtual International Stroke Trials Archive-Imaging ( n = 1300), and Virtual International Stroke Trials Archive-Plus ( n = 6573). Enrollment continues, with commitments for the contribution of six further trials to Virtual International Stroke Trials Archive-Prevention, 13 trials to Virtual International Stroke Trials Archive-Rehab, and one registry to Virtual International Stroke Trials Archive-Plus. Data on age, type of stroke, medical history, outcomes by modified Rankin scale and Barthel Index (BI), mortality, and adverse events are available for analyses. The Virtual International Stroke Trials Archive network encourages the development of young investigators and provides opportunities for international peer review and collaboration. Application of the original Virtual International Stroke Trials Archive concepts beyond acute stroke trials can extend the value of clinical research at low cost, without threatening commercial or intellectual property interests. This delivers valuable research output to inform the efficiency of future stroke research. We invite stroke researchers to participate actively in Virtual International Stroke Trials Archive and encourage the extension of Virtual International Stroke Trials Archive principles to other disease areas.
Publisher: Wiley
Date: 16-10-2014
DOI: 10.1111/ENE.12577
Abstract: Ischaemic stroke patients with atrial fibrillation (AF) are at risk of early recurrent stroke (RS). However, antithrombotics commenced at the acute stage may exacerbate haemorrhagic transformation, provoking symptomatic intracerebral haemorrhage (SICH). The relevance of antithrombotics on the patterns and outcome of the cohort was investigated. A non-randomized cohort analysis was conducted using data obtained from VISTA (Virtual International Stroke Trials Archive). The associations of antithrombotics with the modified Rankin Scale (mRS) outcome and the occurrence of RS and SICH (each as a combined end-point of fatal and non-fatal events) at 90 days for post-stroke patients with AF were described. Dichotomized outcomes were also considered as a secondary end-point (i.e. mortality and good outcome measure at 90 days). In all, 1644 patients were identified 1462 (89%) received antithrombotics, 157 (10%) had RS and 50 (3%) sustained SICH by day 90. Combined antithrombotic therapy (i.e. anticoagulants and antiplatelets), 782 (48%), was associated with favourable outcome on ordinal mRS and a significantly lower risk of RS, SICH and mortality by day 90, compared with the no antithrombotics group. The relative risk of RS and SICH appeared highest in the first 2 days post-stroke before attenuating to become constant over time. The risks and benefits of antithrombotics in recent stroke patients with AF appear to track together. Early introduction of anticoagulants (2-3 days post-stroke), and to a lesser extent antiplatelet agents, was associated with substantially fewer RS events over the following weeks but with no excess risk of SICH. More evidence is required to guide clinicians on this issue.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2003
DOI: 10.1161/01.STR.0000063142.39828.67
Abstract: Background— As increasing numbers of clinical trials are being conducted worldwide, there has been concern about the relationship between the sponsors and investigators. Both parties need benchmarks or recommendations to act as a reference point when trials are initiated and conducted. These recommendations are designed to fulfill this role. Summary of Comment— A series of meetings of the International Trial Subcommittee of the International Stroke Liaison Committee, American Stroke Association, were conducted to review a series of draft recommendations that were then modified on the basis of the experience of the committee in the conduct of clinical trials. Consensus was reached on all points of the final document. The recommendations represent the opinions of the authors and do not necessarily reflect the views of the American Stroke Association. The document contains sensible recommendations concerning required sponsor company qualities, trial management structure, protocol development, trial conduct, data management, blinding, data analyses, publication, remuneration, and conflict of interest issues. Conclusions— The recommendations should provide a simple and practical benchmark for both investigators and sponsors in the conduct of clinical trials. Although designed for trials involving therapies for stroke, the framework allows generalization to other disciplines.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2007
DOI: 10.1161/STROKEAHA.106.473579
Abstract: Background and Purpose— Stroke has global importance and it causes an increasing amount of human suffering and economic burden, but its management is far from optimal. The unsuccessful outcome of several research programs highlights the need for reliable data on which to plan future clinical trials. The Virtual International Stroke Trials Archive aims to aid the planning of clinical trials by collating and providing access to a rich resource of patient data to perform exploratory analyses. Methods— Data were contributed by the principal investigators of numerous trials from the past 16 years. These data have been centrally collated and are available for anonymized analysis and hypothesis testing. Results— Currently, the Virtual International Stroke Trials Archive contains 21 trials. There are data on 000 patients with both ischemic and hemorrhagic stroke. Ages range between 18 and 103 years, with a mean age of 69±12 years. Outcome measures include the Barthel Index, Scandinavian Stroke Scale, National Institutes of Health Stroke Scale, Orgogozo Scale, and modified Rankin Scale. Medical history and onset-to-treatment time are readily available, and computed tomography lesion data are available for selected trials. Conclusions— This resource has the potential to influence clinical trial design and implementation through data analyses that inform planning.
No related grants have been discovered for Markku Kaste.