ORCID Profile
0000-0002-3545-6927
Current Organisations
University of South Australia
,
Flinders University
,
Stanford University
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2011
DOI: 10.1161/STROKEAHA.110.601609
Abstract: To refine the definition of the malignant magnetic resonance imaging profile in acute stroke patients using baseline diffusion-weighted magnetic resonance imaging (DWI) and perfusion-weighted magnetic resonance imaging (PWI) findings from the pooled DEFUSE/EPITHET database. Patients presenting with acute stroke within 3 to 6 hours from symptom onset were treated with tissue plasminogen activator or placebo. Baseline and follow-up DWI and PWI images from both studies were reprocessed using the same software program. A receiver operating characteristic curve analysis was used to identify Tmax and DWI volumes that optimally predicted poor outcomes (modified Rankin Scale 5–6) at 90 days in patients who achieved reperfusion. Sixty-five patients achieved reperfusion and 46 did not reperfuse. Receiver operating characteristic analysis identified a PWI (Tmax s) volume of mL as the optimal definition of the malignant profile. Eighty-nine percent of malignant profile patients had poor outcome with reperfusion versus 39% of patients without reperfusion ( P =0.02). Parenchymal hematomas occurred more frequently in malignant profile patients who experienced reperfusion versus no reperfusion (67% versus 11%, P .01). DWI analysis identified a volume of 80 mL as the best DWI threshold, but this definition was less sensitive than were PWI-based definitions. Stroke patients likely to suffer parenchymal hemorrhages and poor outcomes following reperfusion can be identified from baseline magnetic resonance imaging findings. The current analysis demonstrates that a PWI threshold (Tmax s) of approximately 100 mL is appropriate for identifying these patients. Exclusion of malignant profile patients from reperfusion therapies may substantially improve the efficacy and safety of reperfusion therapies. URL: www.clinicaltrials.gov . Unique identifier: NCT00238537.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 24-05-2022
DOI: 10.1212/WNL.0000000000200269
Abstract: To assess the accuracy of baseline CT perfusion (CTP) ischemic core estimates. From SELECT (Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke), a prospective multicenter cohort study of imaging selection, patients undergoing endovascular thrombectomy who achieved complete reperfusion (modified Thrombolysis In Cerebral Ischemia score 3) and had follow-up diffusion-weighted imaging (DWI) available were evaluated. Follow-up DWI lesions were coregistered to baseline CTP. The difference between baseline CTP core (relative cerebral blood flow [rCBF] %) volume and follow-up infarct volume was classified as overestimation (core ≥10 mL larger than infarct), adequate, or underestimation (core ≥25 mL smaller than infarct) and spatial overlap was evaluated. Of 101 included patients, median time from last known well (LKW) to imaging acquisition was 138 (82–244) minutes. The median baseline ischemic core estimate was 9 (0–31.9) mL and median follow-up infarct volume was 18.4 (5.3–68.7) mL. All 6/101 (6%) patients with overestimation of the subsequent infarct volume were imaged within 90 minutes of LKW and achieved rapid reperfusion (within 120 minutes of CTP). Using rCBF % threshold to estimate ischemic core in patients presenting within 90 minutes eliminated overestimation. Volumetric correlation between the ischemic core estimate and follow-up imaging improved as LKW time to imaging acquisition increased: Spearman ρ minutes 0.33 ( p = 0.049), 90–270 minutes 0.63 ( p 0.0001), minutes 0.86 ( p 0.0001). Assessment of the spatial overlap between baseline CTP ischemic core lesion and follow-up infarct demonstrated that a median of 3.2 (0.0–9.0) mL of estimated core fell outside the subsequent infarct. These regions were predominantly in white matter. Significant overestimation of irreversibly injured ischemic core volume was rare, was only observed in patients who presented within 90 minutes of LKW and achieved reperfusion within 120 minutes of CTP acquisition, and occurred primarily in white matter. Use of a more conservative (rCBF %) threshold for estimating ischemic core in patients presenting within 90 minutes eliminated all significant overestimation cases. ClinicalTrials.gov: NCT03876457.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2016
DOI: 10.1161/STROKEAHA.115.012364
Abstract: The Stroke Imaging Research (STIR) group, the Imaging Working Group of StrokeNet, the American Society of Neuroradiology, and the Foundation of the American Society of Neuroradiology sponsored an imaging session and workshop during the Stroke Treatment Academy Industry Roundtable (STAIR) IX on October 5 to 6, 2015 in Washington, DC. The purpose of this roadmap was to focus on the role of imaging in future research and clinical trials. This forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), industry representatives, and members of the US Food and Drug Administration to discuss STIR priorities in the light of an unprecedented series of positive acute stroke endovascular therapy clinical trials. The imaging session summarized and compared the imaging components of the recent positive endovascular trials and proposed opportunities for pooled analyses. The imaging workshop developed consensus recommendations for optimal imaging methods for the acquisition and analysis of core, mismatch, and collaterals across multiple modalities, and also a standardized approach for measuring the final infarct volume in prospective clinical trials. Recent positive acute stroke endovascular clinical trials have demonstrated the added value of neurovascular imaging. The optimal imaging profile for endovascular treatment includes large vessel occlusion, smaller core, good collaterals, and large penumbra. However, equivalent definitions for the imaging profile parameters across modalities are needed, and a standardization effort is warranted, potentially leveraging the pooled data resulting from the recent positive endovascular trials.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2013
DOI: 10.1161/STROKEAHA.112.668301
Abstract: Two phase 2 studies of alteplase in acute ischemic stroke 3 to 6 hours after onset, Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET a randomized, controlled, double-blinded trial), and Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study (DEFUSE open-label, treatment only) using MR imaging-based outcomes have been conducted. We have pooled in idual patient data from these to assess the response to alteplase. The primary hypothesis was that alteplase would significantly attenuate infarct growth compared with placebo in mismatch-selected patients using coregistration techniques. The EPITHET–DEFUSE study datasets were pooled while retaining the original inclusion and exclusion criteria. Significant hypoperfusion was defined as a Tmax delay seconds), and coregistration techniques were used to define MR diffusion-weighted imaging erfusion-weighted imaging mismatch. Neuroimaging, parameters including reperfusion, recanalization, symptomatic intracerebral hemorrhage, and clinical outcomes were assessed. Alteplase and placebo groups were compared for the primary outcome of infarct growth as well for secondary outcome measures. From 165 patients with adequate MR scans in the EPITHET–DEFUSE pooled data, 121 patients (73.3%) were found to have mismatch. For the primary outcome analysis, 60 patients received alteplase and 41 placebo. Mismatch patients receiving alteplase had significantly attenuated infarct growth compared with placebo ( P =0.025). The reperfusion rate was also increased (62.7% vs 31.7% P =0.003). Mortality and clinical outcomes were not different between groups. The data provide further evidence that alteplase significantly attenuates infarct growth and increases reperfusion compared with placebo in the 3- to 6- hour time window in patients selected based on MR penumbral imaging. URL: www.clinicaltrials.gov . Unique identifier: NCT00238537
Publisher: Frontiers Media SA
Date: 13-05-2017
Publisher: SAGE Publications
Date: 31-12-2015
Abstract: Recent trials have shown a clear benefit of endovascular therapy for stroke patients presenting within 6 h after stroke onset. Imaging-based selection may identify a cohort with a favorable response to endovascular therapy, in an even later time window. We performed an indirect comparison between outcomes seen in DEFUSE 2, a prospective cohort study of patients who received a baseline MRI before endovascular therapy, and a control group from AXIS 2 receiving standard medical care up to 12 h after symptom onset. Patients from AXIS 2 with a confirmed large vessel occlusion were selected as a control group for DEFUSE 2-patients. The primary endpoint was good functional outcome at day 90 (Modified Rankin Score 0–2). We performed a stratified analysis based on the presence of the target mismatch for both studies and reperfusion status in DEFUSE 2. We compared good functional outcome in 108 patients from AXIS 2 and 99 patients from DEFUSE 2. In DEFUSE 2-patients with the target mismatch profile in whom reperfusion was achieved, the rate of good functional outcome was increased compared to target mismatch patients in AXIS 2, 54% versus 29% (OR 3.2, 95% CI 1.1–9.4). In target mismatch patients treated between 6 and 12 h after stroke onset, this association between study and good functional outcome remained present (OR 9.0, 95% CI 1.1–75.8). This indirect comparison suggests that endovascular treatment resulting in substantial reperfusion is associated with improved outcome in target mismatch patients even beyond 6 h after stroke onset. Confirmation is needed from future clinical trials that randomize patients beyond the 6 h time window.
Publisher: SAGE Publications
Date: 23-12-2013
DOI: 10.1111/IJS.12230
Abstract: Reperfusion is associated with good functional outcome after stroke. However, minimal data are available regarding the effect of reperfusion on clinical outcome and infarct growth in patients with distal MCA branch occlusions. The aim of this study was to evaluate this association and to determine the impact of the perfusion-diffusion mismatch. In idual patient data from three stroke studies (EPITHET, DEFUSE and DEFUSE 2) with baseline MRI profiles and reperfusion status were pooled. Patients were included if they had a single cortical perfusion lesion on their baseline MRI that was consistent with a distal MCA branch occlusion. Good functional outcome was defined as a score of 0–2 on the modified Rankin Scale at day 90 and infarct growth was defined as change in lesion volume between the baseline DWI and the final T2/FLAIR. Thirty patients met inclusion criteria. Eighteen (60%) had a good functional outcome and twenty (67%) had reperfusion. Reperfusion was not associated with good functional outcome in the overall cohort (OR: 1·0, 95% CI 0·2–4·7) and also not in the subset of patients with a PWI-DWI mismatch ( n = 17 OR: 0·7, 95% CI 0·1–5·5). Median infarct growth was modest and not significantly different between patients with (0 ml) and without reperfusion (6 ml) P = 0·2. The overall high rate of good outcomes in patients with distal MCA perfusion lesions might obscure a potential benefit from reperfusion in this population. A larger pooled analysis evaluating the effect of reperfusion in patients with distal MCA branch occlusions is warranted as confirmation of our results could have implications for the design of future stroke trials.
Publisher: Wiley
Date: 26-02-2013
DOI: 10.1002/ANA.23837
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2021
DOI: 10.1161/STROKEAHA.120.030696
Abstract: The ISLES challenge (Ischemic Stroke Lesion Segmentation) enables globally erse teams to compete to develop advanced tools for stroke lesion analysis with machine learning. Detection of irreversibly damaged tissue on computed tomography perfusion (CTP) is often necessary to determine eligibility for late-time-window thrombectomy. Therefore, the aim of ISLES-2018 was to segment infarcted tissue on CTP based on diffusion-weighted imaging as a reference standard. The data, from 4 centers, consisted of 103 cases of acute anterior circulation large artery occlusion stroke who underwent diffusion-weighted imaging rapidly after CTP. Diffusion-weighted imaging lesion segmentation was performed manually and acted as a reference standard. The data were separated into 63 cases for training and 40 for testing, upon which quality metrics (dice score coefficient, Hausdorff distance, absolute lesion volume difference, etc) were computed to rank methods based on their overall performance. Twenty-four different teams participated in the challenge. Median time to CTP was 185 minutes (interquartile range, 180–238), the time between CTP and magnetic resonance imaging was 36 minutes (interquartile range, 25–79), and the median infarct lesion size was 15.2 mL (interquartile range, 5.7–45). The best performance for Dice score coefficient and absolute volume difference were 0.51 and 10.1 mL, respectively, from different teams. Based on the ranking criteria, the top team’s algorithm demonstrated for average Dice score coefficient and average absolute volume difference 0.51 and 10.2 mL, respectively, outperforming the conventional threshold-based method (dice score coefficient, 0.3 volume difference, 15.3). Diverse algorithms were used, almost all based on deep learning, with top-ranked approaches making use of the raw perfusion data as well as methods to synthetically generate complementary information to boost prediction performance. Machine learning methods may predict infarcted tissue from CTP with improved accuracy compared with threshold-based methods used in clinical routine. This dataset will remain public and can be used to test improvement in algorithms over time.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2011
DOI: 10.1161/STROKEAHA.110.609008
Abstract: The aim of this study was to determine if automated MRI analysis software (RAPID) can be used to identify patients with stroke in whom reperfusion is associated with an increased chance of good outcome. Baseline diffusion- and perfusion-weighted MRI scans from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution study (DEFUSE n=74) and the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET n=100) were reprocessed with RAPID. Based on RAPID-generated diffusion-weighted imaging and perfusion-weighted imaging lesion volumes, patients were categorized according to 3 prespecified MRI profiles that were hypothesized to predict benefit (Target Mismatch), harm (Malignant), and no effect (No Mismatch) from reperfusion. Favorable clinical response was defined as a National Institutes of Health Stroke Scale score of 0 to 1 or a ≥8-point improvement on the National Institutes of Health Stroke Scale score at Day 90. In Target Mismatch patients, reperfusion was strongly associated with a favorable clinical response (OR, 5.6 95% CI, 2.1 to 15.3) and attenuation of infarct growth (10±23 mL with reperfusion versus 40±44 mL without reperfusion P .001). In Malignant profile patients, reperfusion was not associated with a favorable clinical response (OR, 0.74 95% CI, 0.1 to 5.8) or attenuation of infarct growth (85±74 mL with reperfusion versus 95±79 mL without reperfusion P =0.7). Reperfusion was also not associated with a favorable clinical response (OR, 1.05 95% CI, 0.1 to 9.4) or attenuation of lesion growth (10±15 mL with reperfusion versus 17±30 mL without reperfusion P =0.9) in No Mismatch patients. MRI profiles that are associated with a differential response to reperfusion can be identified with RAPID. This supports the use of automated image analysis software such as RAPID for patient selection in acute stroke trials.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-01-2022
DOI: 10.1212/WNL.0000000000201384
Abstract: The effect of anesthesia choice on endovascular thrombectomy (EVT) outcomes is unclear. Collateral status on perfusion imaging may help identify the optimal anesthesia choice. In a pooled patient-level analysis of EXTEND-IA, EXTEND-IA TNK, EXTEND-IA TNK part II, and SELECT, EVT functional outcomes (modified Rankin Scale score distribution) were compared between general anesthesia (GA) vs non-GA in a propensity-matched s le. Furthermore, we evaluated the association of collateral flow on perfusion imaging, assessed by hypoperfusion intensity ratio (HIR) – Tmax 10 seconds/Tmax 6 seconds (good collaterals – HIR 0.4, poor collaterals – HIR ≥ 0.4) on the association between anesthesia type and EVT outcomes. Of 725 treated with EVT, 299 (41%) received GA and 426 (59%) non-GA. The baseline characteristics differed in presentation National Institutes of Health Stroke Scale score (median [interquartile range] GA: 18 [13–22], non-GA: 16 [11–20], p 0.001) and ischemic core volume (GA: 15.0 mL [3.2–38.0] vs non-GA: 9.0 mL [0.0–31.0], p 0.001). In addition, GA was associated with longer last known well to arterial access (203 minutes [157–267] vs 186 minutes [138–252], p = 0.002), but similar procedural time (35.5 minutes [23–59] vs 34 minutes [22–54], p = 0.51). Of 182 matched pairs using propensity scores, baseline characteristics were similar. In the propensity score–matched pairs, GA was independently associated with worse functional outcomes (adjusted common odds ratio [adj. cOR]: 0.64, 95% CI: 0.44–0.93, p = 0.021) and higher neurologic worsening (GA: 14.9% vs non-GA: 8.9%, aOR: 2.10, 95% CI: 1.02–4.33, p = 0.045). Patients with poor collaterals had worse functional outcomes with GA (adj. cOR: 0.47, 95% CI: 0.29–0.76, p = 0.002), whereas no difference was observed in those with good collaterals (adj. cOR: 0.93, 95% CI: 0.50–1.74, p = 0.82), p interaction : 0.07. No difference was observed in infarct growth overall and in patients with good collaterals, whereas patients with poor collaterals demonstrated larger infarct growth with GA with a significant interaction between collaterals and anesthesia type on infarct growth rate ( p interaction : 0.020). GA was associated with worse functional outcomes after EVT, particularly in patients with poor collaterals in a propensity score–matched analysis from a pooled patient-level cohort from 3 randomized trials and 1 prospective cohort study. The confounding by indication may persist despite the doubly robust nature of the analysis. These findings have implications for randomized trials of GA vs non-GA and may be of utility for clinicians when making anesthesia type choice. This study provides Class III evidence that use of GA is associated with worse functional outcome in patients undergoing EVT. EXTEND-IA: ClinicalTrials.gov (NCT01492725) EXTEND-IA TNK: ClinicalTrials.gov (NCT02388061) EXTEND-IA TNK part II: ClinicalTrials.gov (NCT03340493) and SELECT: ClinicalTrials.gov (NCT02446587).
Publisher: Elsevier BV
Date: 11-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2006
DOI: 10.1161/01.STR.0000239696.61545.4B
Abstract: Background and Purpose— Since the failure of a number of phase III trials of neuroprotection in ischemic stroke, the need for smaller phase II studies with MRI surrogates has emerged. There is, however, little information available about s le size requirements for such phase II trials and rarely enough patients in single studies to make robust estimates. We have formed an international collaborative group to assemble larger datasets and from these have generated s le size tables for MRI-based infarct expansion as the outcome measure. Methods— Twelve centers from Australia, Europe, and North America contributed data from patients with hemispheric ischemic stroke. Infarct expansion was defined from initial diffusion-weighted images and later fluid-attenuated inversion recover or T 2 images. S le size estimates were calculated from data on infarct expansion ratios treated as dichotomous or continuous variables. A nonparametric approach was used because the distribution of infarct expansion was resistant to all forms of transformation. Results— As an ex le, a 20% absolute reduction in infarct expansion ratio (≤1), 80% power, and α=0.05 requires 99 patients in each arm. To achieve an equivalent effect size with a continuous approach requires 61 patients. Conclusions— These tables will be useful in planning phase II trials of therapy with the use of MRI outcome measures. For positive studies, biologically plausible surrogates such as these may provide a rationale for proceeding to phase III trials.
Publisher: SAGE Publications
Date: 18-01-2016
Abstract: For the STroke Imaging Research (STIR) and VISTA-Imaging Investigators The purpose of this study was to collect precise information on the typical imaging decisions given specific clinical acute stroke scenarios. Stroke centers worldwide were surveyed regarding typical imaging used to work up representative acute stroke patients, make treatment decisions, and willingness to enroll in clinical trials. STroke Imaging Research and Virtual International Stroke Trials Archive-Imaging circulated an online survey of clinical case vignettes through its website, the websites of national professional societies from multiple countries as well as through email distribution lists from STroke Imaging Research and participating societies. Survey responders were asked to select the typical imaging work-up for each clinical vignette presented. Actual images were not presented to the survey responders. Instead, the survey then displayed several types of imaging findings offered by the imaging strategy, and the responders selected the appropriate therapy and whether to enroll into a clinical trial considering time from onset, clinical presentation, and imaging findings. A follow-up survey focusing on 6 h from onset was conducted after the release of the positive endovascular trials. We received 548 responses from 35 countries including 282 in idual centers 78% of the centers originating from Australia, Brazil, France, Germany, Spain, United Kingdom, and United States. The specific onset windows presented influenced the type of imaging work-up selected more than the clinical scenario. Magnetic Resonance Imaging usage (27–28%) was substantial, in particular for wake-up stroke. Following the release of the positive trials, selection of perfusion imaging significantly increased for imaging strategy. Usage of vascular or perfusion imaging by Computed Tomography or Magnetic Resonance Imaging beyond just parenchymal imaging was the primary work-up (62–87%) across all clinical vignettes and time windows. Perfusion imaging with Computed Tomography or Magnetic Resonance Imaging was associated with increased probability of enrollment into clinical trials for 0–3 h. Following the release of the positive endovascular trials, selection of endovascular only treatment for 6 h increased across all clinical vignettes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2010
Publisher: Massachusetts Medical Society
Date: 06-04-2023
Publisher: Elsevier BV
Date: 08-2009
Publisher: Wiley
Date: 18-06-2014
DOI: 10.1111/JON.12130
Abstract: The posterior circulation Acute Stroke Prognosis Early CT Score (pc-APECTS) applied to CT angiography source images (CTA-SI) predicts the functional outcome of patients in the Basilar Artery International Cooperation Study (BASICS). We assessed the diagnostic and prognostic impact of pc-ASPECTS applied to perfusion CT (CTP) in the BASICS registry population. We applied pc-ASPECTS to CTA-SI and cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) parameter maps of BASICS patients with CTA and CTP studies performed. Hypoattenuation on CTA-SI, relative reduction in CBV or CBF, or relative increase in MTT were rated as abnormal. CTA and CTP were available in 27/592 BASICS patients (4.6%). The proportion of patients with any perfusion abnormality was highest for MTT (93% 95% confidence interval [CI], 76%-99%), compared with 78% (58%-91%) for CTA-SI and CBF, and 46% (27%-67%) for CBV (P < .001). All 3 patients with a CBV pc-ASPECTS < 8 compared to 6/23 patients with a CBV pc-ASPECTS ≥ 8 had died at 1 month (RR 3.8 95% CI, 1.9-7.6). CTP was performed in a minority of the BASICS registry population. Perfusion disturbances in the posterior circulation were most pronounced on MTT parameter maps. CBV pc-ASPECTS < 8 may indicate patients with high case fatality.
Publisher: SAGE Publications
Date: 15-12-2022
DOI: 10.1177/17474930211035032
Abstract: Randomized evidence for endovascular thrombectomy safety and efficacy in patients with large core strokes is lacking. To demonstrate endovascular thrombectomy efficacy and safety in patients with large core on non-contrast CT or perfusion imaging (CT/MR) and determine if there is heterogeneity of treatment effect in large cores based on the imaging modality. SELECT2 is a prospective, randomized, multi-center, assessor-blinded controlled trial with adaptive enrichment design, enrolling up to 560 patients. Patients who meet the clinical criteria and have anterior circulation large vessel occlusions with large core on either NCCT (ASPECTS 3-5) or perfusion imaging (CTP [rCBF < 30%] and/or MRI [ADC < 620] ≥ 50 cc) will be randomized in a 1:1 ratio to undergo endovascular thrombectomy or medical management (MM) only up to 24 h of last known well. The distribution of 90-day mRS scores is the primary outcome. Functional independence (mRS = 0-2) rate is a secondary outcome. Other secondary outcomes include safety (symptomatic ICH, neurological worsening, mortality) and imaging outcomes. A normal approximation of the Wilcoxon-Mann-Whitney test (the generalized likelihood ratio test) to assess the primary outcome. Functional independence rates, safety and imaging outcomes will also be compared. The SELECT2 trial will evaluate endovascular thrombectomy safety and efficacy in large cores on either CT or perfusion imaging and may provide randomized evidence to extend endovascular thrombectomy eligibility to larger population.
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: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2021
DOI: 10.1161/STROKEAHA.121.035132
Abstract: The Stroke Treatment Academic Industry Roundtable (STAIR) sponsored an imaging session and workshop during the Stroke Treatment Academic Industry Roundtable XI via webinar on October 1 to 2, 2020, to develop consensus recommendations, particularly regarding optimal imaging at primary stroke centers. This forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke, industry representatives, and members of the US Food and Drug Administration to discuss imaging priorities in the light of developments in reperfusion therapies, particularly in an extended time window, and reinvigorated interest in brain cytoprotection trials. The imaging session summarized and compared the imaging components of recent acute stroke trials and debated the optimal imaging strategy at primary stroke centers. The imaging workshop developed consensus recommendations for optimizing the acquisition, analysis, and interpretation of computed tomography and magnetic resonance acute stroke imaging, and also recommendations on imaging strategies for primary stroke centers. Recent positive acute stroke clinical trials have extended the treatment window for reperfusion therapies using imaging selection. Achieving rapid and high-quality stroke imaging is therefore critical at both primary and comprehensive stroke centers. Recommendations for enhancing stroke imaging research are provided.
Publisher: SAGE Publications
Date: 04-2022
DOI: 10.1177/17474930221088400
Abstract: While thrombolysis is standard of care for patients with acute ischemic stroke (AIS) within 4.5 h of symptom onset, the benefit of tenecteplase beyond this time window is less certain. The TIMELESS trial (NCT03785678) aims to determine if treatment with tenecteplase increases the proportion of good clinical outcomes among patients with stroke due to a large vessel occlusion who present beyond 4.5 h after symptom onset. A total of 456 patients will provide ⩾90% power to detect differences in the distribution of modified Rankin Scale scores at Day 90 at the two-sided 0.049 significance level. TIMELESS is a Phase III, double-blind, randomized, placebo-controlled trial of tenecteplase with or without endovascular thrombectomy in patients with AIS and evidence of salvageable tissue via imaging who present within the 4.5- to 24-h time window with an internal carotid artery (ICA) or middle cerebral artery (MCA) (M1/M2) occlusion. The primary efficacy objective of tenecteplase compared with placebo will be evaluated with ordinal modified Rankin Scale scores at Day 90. Safety will be evaluated via incidence of symptomatic intracranial hemorrhage, incidence and severity of adverse events, and mortality rate. Results from TIMELESS will contribute to understanding of the safety and efficacy of tenecteplase administered 4.5–24 h following symptom onset for patients with an ICA or MCA occlusion.
Publisher: SAGE Publications
Date: 12-03-2013
DOI: 10.1111/IJS.12007
Abstract: Atrial fibrillation is associated with greater baseline neurological impairment and worse outcomes following ischemic stroke. Previous studies suggest that greater volumes of more severe baseline hypoperfusion in patients with history of atrial fibrillation may explain this association. We further investigated this association by comparing patients with and without atrial fibrillation on initial examination following stroke using pooled multimodal magnetic resonance imaging and clinical data from the Echoplanar Imaging Thrombolytic Evaluation Trial and the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution studies. Echoplanar Imaging Thrombolytic Evaluation Trial was a trial of 101 ischemic stroke patients randomized to intravenous tissue plasminogen activator or placebo, and Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution was a prospective cohort of 74 ischemic stroke patients treated with intravenous tissue plasminogen activator at three to six hours following symptom onset. Patients underwent multimodal magnetic resonance imaging before treatment, at three to five days and three-months after stroke in Echoplanar Imaging Thrombolytic Evaluation Trial before treatment, three to six hours after treatment and one-month after stroke in Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution. Patients were assessed with the National Institutes of Health Stroke Scale and the modified Rankin scale before treatment and at three-months after stroke. Patients were categorized into definite atrial fibrillation (present on initial examination), probable atrial fibrillation (history but no atrial fibrillation on initial examination), and no atrial fibrillation. Perfusion data were reprocessed with automated magnetic resonance imaging analysis software (RAPID, Stanford University, Stanford, CA, USA). Hypoperfusion volumes were defined using time to maximum delays in two-second increments from to s. Hemorrhagic transformation was classified according to the European Cooperative Acute Stroke Studies criteria. Of the 175 patients, 28 had definite atrial fibrillation, 30 probable atrial fibrillation, 111 no atrial fibrillation, and six were excluded due to insufficient imaging data. At baseline, patients with definite atrial fibrillation had more severe hypoperfusion (median time to maximum s, volume 48 vs. 29 ml, P = 0·02) compared with patients with no atrial fibrillation. At outcome, patients with definite atrial fibrillation had greater infarct growth (median volume 47 vs. 8 ml, P = 0·001), larger infarcts (median volume 75 vs. 23 ml, P = 0·001), more frequent parenchymal hematoma grade hemorrhagic transformation (30% vs. 10%, P = 0·03), worse functional outcomes (median modified Rankin scale score 4 vs. 3, P = 0·03), and higher mortality (36% vs. 16%, P = 0·03) compared with patients with no atrial fibrillation. Definite atrial fibrillation was independently associated with increased parenchymal hematoma (odds ratio = 6·05, 95% confidence interval 1·60–22·83) but not poor functional outcome (modified Rankin scale 3–6, odds ratio = 0·99, 95% confidence interval 0·35–2·80) or mortality (odds ratio = 2·54, 95% confidence interval 0·86–7·49) three-months following stroke, after adjusting for other baseline imbalances. Atrial fibrillation is associated with greater volumes of more severe baseline hypoperfusion, leading to higher infarct growth, more frequent severe hemorrhagic transformation and worse stroke outcomes.
Publisher: SAGE Publications
Date: 22-07-2016
Abstract: Differences in research methodology have h ered the optimization of Computer Tomography Perfusion (CTP) for identification of the ischemic core. We aim to optimize CTP core identification using a novel benchmarking tool. The benchmarking tool consists of an imaging library and a statistical analysis algorithm to evaluate the performance of CTP. The tool was used to optimize and evaluate an in-house developed CTP-software algorithm. Imaging data of 103 acute stroke patients were included in the benchmarking tool. Median time from stroke onset to CT was 185 min (IQR 180-238), and the median time between completion of CT and start of MRI was 36 min (IQR 25-79). Volumetric accuracy of the CTP-ROIs was optimal at an rCBF threshold of % at this threshold, the mean difference was 0.3 ml (SD 19.8 ml), the mean absolute difference was 14.3 (SD 13.7) ml, and CTP was 67% sensitive and 87% specific for identification of DWI positive tissue voxels. The benchmarking tool can play an important role in optimizing CTP software as it provides investigators with a novel method to directly compare the performance of alternative CTP software packages.
Publisher: SAGE Publications
Date: 27-06-2013
DOI: 10.1111/IJS.12068
Abstract: MRI-based selection of patients for acute stroke interventions requires rapid accurate estimation of the infarct core on diffusion-weighted MRI. Typically used manual methods to delineate restricted diffusion lesions are subjective and time consuming. These limitations would be overcome by a fully automated method that can rapidly and objectively delineate the ischemic core. An automated method would require predefined criteria to identify the ischemic core. The aim of this study is to determine apparent diffusion coefficient-based criteria that can be implemented in a fully automated software solution for identification of the ischemic core. Imaging data from patients enrolled in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) study who had early revascularization following intravenous thrombolysis were included. The patients' baseline restricted diffusion and 30–day T 2 -weighted fluid-attenuated inversion recovery lesions were manually delineated after coregistration. Parts of the restricted diffusion lesion that corresponded with 30-day infarct were considered ischemic core, whereas parts that corresponded with normal brain parenchyma at 30 days were considered noncore. The optimal apparent diffusion coefficient threshold to discriminate core from noncore voxels was determined by voxel-based receiver operating characteristics analysis using the Youden index. 51 045 diffusion positive voxels from 14 patients who met eligibility criteria were analyzed. The mean DWI lesion volume was 24 (± 23) ml. Of this, 18 (± 22) ml was ischemic core and 3 (± 5) ml was noncore. The remainder corresponded to preexisting gliosis, cerebrospinal fluid, or was lost to postinfarct atrophy. The apparent diffusion coefficient of core was lower than that of noncore voxels ( P 0·0001). The optimal threshold for identification of ischemic core was an apparent diffusion coefficient ≤620 × 10 −6 mm 2 /s (sensitivity 69% and specificity 78%). Our data suggest that the ischemic core can be identified with an absolute apparent diffusion coefficient threshold. This threshold can be implemented in image analysis software for fully automated segmentation of the ischemic core.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Australian College of Perioperative Nurses
Date: 03-2017
Publisher: Wiley
Date: 11-05-2023
DOI: 10.1111/JOCN.16746
Abstract: To systematically identify, appraise and synthesise qualitative studies investigating Registered Nurse students' (RNS) experiences of workplace violence (WPV) while on clinical placement. It is expected that the literature review findings will guide the development of targeted programs and policies to address WPV against RNS. WPV affects RNS during clinical placements as they are vulnerable to violence due to their limited experience and skills to challenge abusive behaviour. In this review, RNS are students enrolled in a Bachelor of Nursing program to become registered nurses and exclude students who are enrolled in nursing program that does not lead to registration as a registered nurse. For ex le, enrolled in nursing programs and postgraduate nursing programs. RNS are chosen for their scope of practice and the training requirements. RNS reported experiencing WPV mainly from colleagues, staff, teachers, doctors and supervisors, which resulted in leaving nursing practice, impacting students' progression and healthcare systems. This review examines all types of violence RNS face irrespective of the abuser. A qualitative systematic review of existing literature was conducted through a comprehensive database search of eight databases MEDLINE, CINAHL, Web of Science, Scopus, Embase, Cochrane Central and ProQuest. Furthermore, reference lists of included studies were searched to identify further research. English language qualitative primary studies of any study design were searched from inception to 6th June 2022 and included if they met the inclusion criteria. Double review process utilised from screening until data synthesis reported according to PRISMA. JBI critical appraisal tools were used to assess the studies, and data extraction utilised JBI QARI tool and screened for credibility and confidence in findings. A total of 18 studies met the inclusion criteria, and the studies were conducted in nine countries. Five main themes relating to RNS experiences of WPV while on clinical placement were identified, including: ‘Types of workplace violence’, ‘Perpetrators’, ‘Causes’, ‘Consequences’ and ‘Management of workplace violence’. This qualitative systematic review provides new and significant knowledge in understanding the phenomenon of WPV experienced by RNS while on clinical placement. This review highlights the unwillingness of RNS to reach out to instructors or clinical placement leaders in many situations and identifies avenues of support and awareness that are crucial to empower and enabling students to seek support.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Informa UK Limited
Date: 06-02-2014
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: SAGE Publications
Date: 16-10-2014
DOI: 10.1111/IJS.12381
Abstract: Advanced imaging may refine patient selection for ischemic stroke treatment but delays to acquire and process the imaging have limited implementation. We examined the feasibility of imaging selection in clinical practice using fully automated software in the EXTEND trial program. CTP and perfusion-diffusion MRI data were processed using fully-automated software to generate a yes/no ‘mismatch’ classification that determined eligibility for trial therapies. The technical failure/mismatch classification error rate and time to image and treat with CT vs. MR-based selection were examined. In a consecutive series of 776 patients from five sites over six-months the technical failure rate of CTP acquisition rocessing (uninterpretable maps) was 3·4% (26/776, 95%CI 2·2–4·9%). Mismatch classification was overruled by expert review in an additional 9·0% (70/776, 95%CI 7·1–11·3%) due to artifactual ‘perfusion lesion’. In 154 consecutive patients at one site, median additional time to acquire CTP after noncontrast CT was 6·5 min. Subsequent RAPID processing time varied from 3–10 min across 20 trial centers (median 5 min 20 s). In the EXTEND trial, door-to-needle times in patients randomized on the basis of CTP ( n = 47) were median 78 min shorter than MRI-selected ( n = 16) patients ( P 0·001). Automated CTP-based mismatch selection is rapid, robust in clinical practice, and associated with faster treatment decisions than MRI. This technological advance has the potential to improve the standardization and reproducibility of interpretation of advanced imaging and extend use to practice settings beyond highly specialized academic centers.
Publisher: SAGE Publications
Date: 02-2018
Abstract: Mechanical thrombectomy within 6 h after stroke onset improves the outcome in patients with large vessel occlusions. The aim of our study was to establish a model based on diffusion weighted and perfusion weighted imaging to provide an accurate prediction for the 6 h time-window in patients with unknown time of stroke onset. A predictive model was designed based on data from the DEFUSE 2 study and validated in a subgroup of patients with large vessel occlusions from the AXIS 2 trial. We constructed the model in 91 patients from DEFUSE 2. The following parameters were independently associated with h time-window and included in the model: interquartile range and median relative diffusion weighted imaging, hypoperfusion intensity ratio, core volume and the interaction between median relative diffusion weighted imaging and hypoperfusion intensity ratio as predictors of the 6 h time-window. The area under the curve was 0.80 with a positive predictive value of 0.90 (95%CI 0.79–0.96). In the validation cohort (N = 90), the area under the curve was 0.73 ( P for difference = 0.4) with a positive predictive value of 0.85 (95%CI 0.69–0.95). After validation in a larger independent dataset the model can be considered to select patients for endovascular treatment in whom stroke onset is unknown. In patients with large vessel occlusion and unknown time of stroke onset an automated multivariate imaging model is able to select patients who are likely within the 6 h time-window.
Publisher: Wiley
Date: 10-2011
DOI: 10.1002/ANA.22444
Publisher: SAGE Publications
Date: 20-07-2011
Abstract: Diffusion-weighted imaging (DWI) is commonly used to assess irreversibly infarcted tissue but its accuracy is challenged by reports of diffusion lesion reversal (DLR). We investigated the frequency and implications for mismatch classification of DLR using imaging from the EPITHET (Echoplanar Imaging Thrombolytic Evaluation Trial) and DEFUSE (Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution) studies. In 119 patients (83 treated with IV tissue plasminogen activator), follow-up images were coregistered to acute diffusion images and the lesions manually outlined to their maximal visual extent in diffusion space. Diffusion lesion reversal was defined as voxels of acute diffusion lesion that corresponded to normal brain at follow-up (i.e., final infarct, leukoaraiosis, and cerebrospinal fluid (CSF) voxels were excluded from consideration). The appearance of DLR was visually checked for artifacts, the volume calculated, and the impact of adjusting baseline diffusion lesion volume for DLR volume on perfusion-diffusion mismatch analyzed. Median DLR volume reduced from 4.4 to 1.5 mL after excluding CSF/leukoaraiosis. Visual inspection verified 8/119 (6.7%) with true DLR, median volume 2.33 mL. Subtracting DLR from acute diffusion volume altered perfusion—diffusion mismatch ( T max seconds, ratio .2) in 3/119 (2.5%) patients. Diffusion lesion reversal between baseline and 3 to 6 hours DWI was also uncommon (7/65, 11%) and often transient. Clinically relevant DLR is uncommon and rarely alters perfusion—diffusion mismatch. The acute diffusion lesion is generally a reliable signature of the infarct core.
Publisher: S. Karger AG
Date: 2011
DOI: 10.1159/000331467
Abstract: i Background: /i Fluid-attenuated inversion recovery (FLAIR) hyperintensity within an acute cerebral infarct may reflect delayed onset time and increased risk of hemorrhage after thrombolysis. Given the important implications for clinical practice, we examined the prevalence of FLAIR hyperintensity in patients 3–6 h from stroke onset and its relationship to parenchymal hematoma (PH). i Methods: /i Baseline DWI and FLAIR imaging with subsequent hemorrhage detection (ECASS criteria) were prospectively obtained in patients 3–6 h after stroke onset from the pooled EPITHET and DEFUSE trials. FLAIR hyperintensity within the region of the acute DWI lesion was rated qualitatively (dichotomized as visually obvious or subtle (i.e. only visible after careful windowing)) and quantitatively (using relative signal intensity (RSI)). The association of FLAIR hyperintensity with hemorrhage was then tested alongside established predictors (very low cerebral blood volume (VLCBV) and diffusion (DWI) lesion volume) in logistic regression analysis. i Results: /i There were 49 patients with pre-treatment FLAIR imaging (38 received tissue plasminogen activator (tPA), 5 developed PH). FLAIR hyperintensity within the region of acute DWI lesion occurred in 48/49 (98%) patients, was obvious in 18/49 (37%) and subtle in 30/49 (61%). Inter-rater agreement was 92% (ĸ = 0.82). The prevalence of obvious FLAIR hyperintensity did not differ between studies obtained in the 3–4.5 h and 4.5–6 h time periods (40% vs. 33%, p = 0.77). PH was poorly predicted by obvious FLAIR hyperintensity (sensitivity 40%, specificity 64%, positive predictive value 11%). In univariate logistic regression, VLCBV (p = 0.02) and DWI lesion volume (p = 0.03) predicted PH but FLAIR lesion volume (p = 0.87) and RSI (p = 0.11) did not. In ordinal logistic regression for hemorrhage grade adjusted for age and baseline stroke severity (NIHSS), increased VLCBV (p = 0.002) and DWI lesion volume (p = 0.003) were associated with hemorrhage but FLAIR lesion volume (p = 0.66) and RSI (p = 0.35) were not. i Conclusions: /i Visible FLAIR hyperintensity is almost universal 3–6 h after stroke onset and did not predict subsequent hemorrhage in this dataset. Our findings question the value of excluding patients with FLAIR hyperintensity from reperfusion therapies. Larger studies are required to clarify what implications FLAIR-positive lesions have for patient selection.
No related grants have been discovered for Maarten Lansberg.