ORCID Profile
0000-0003-3632-9433
Current Organisations
Aix-Marseille Université
,
Royal Australasian College of Physicians
,
University of Melbourne
,
Royal Melbourne Hospital
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Publisher: S. Karger AG
Date: 2010
DOI: 10.1159/000311080
Abstract: i Background: /i For MR perfusion-diffusion mismatch to be clinically useful as a means of selecting patients for thrombolysis, it needs to occur in real time at the MRI console. Visual mismatch assessment has been used clinically and in trials but has not been systematically validated. We compared the accuracy of visually rating console-generated images with offline volumetric measurements using data from the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET). i Methods: /i Perfusion time-to-peak (TTP) and diffusion-weighted images (DWI) (as generated by commercial MRI console software) and T sub max /sub perfusion maps (which required offline calculation) were visually rated. Perfusion-diffusion mismatch, defined as a ratio of perfusion:diffusion lesion volume of .2, was independently scored by 1 expert and 2 inexperienced raters blinded to calculated volumes and clinical information. Visual mismatch was compared with region-of-interest-based volumetric calculation, which was used as the gold standard. i Results: /i Volumetric calculation demonstrated perfusion-diffusion mismatch in 85/99 patients. Visual TTP-DWI mismatch was correctly classified by the experienced rater in 82% of the cases (sensitivity: 0.86 specificity: 0.54) compared to 73% for the inexperienced raters (sensitivity: 0.75 specificity: 0.57). The interrater reliability for TTP-DWI mismatch was moderate (ĸ = 0.50). Visual T sub max /sub -DWI mismatch performed better (agreement – 93 and 87%, sensitivity – 95 and 88%, specificity – 77 and 82% for the experienced and inexperienced raters, respectively). i Conclusions: /i The assessment of visual TTP-DWI mismatch at the MRI console is insufficiently reliable for use in clinical trials. Differences in perfusion analysis technique and visual inaccuracies combine to make visual TTP-DWI mismatch substantially different to volumetric T sub max /sub -DWI mismatch. Automated software that applies perfusion thresholds may improve the reproducibility of real-time mismatch assessment.
Publisher: Elsevier BV
Date: 03-2012
DOI: 10.1016/J.JOCN.2011.08.014
Abstract: Thrombolysis trials have recruited few patients aged ≥80 years, which has led to uncertainty about the likely risk-to-benefit profile in the elderly. Leukoaraiosis (LA) has been associated with hemorrhagic transformation (HT) and increases with advanced age. We tested whether there were any independent associations between age, LA and HT. Consecutive patients treated with intravenous (IV) tissue plasminogen activator (tPA) were identified from a prospective database. LA on baseline CT scans was assessed by two independent raters using the modified Van Swieten Score (mVSS) (maximum score 8, severe >4). HT was assessed on routine 24 hour to 48 hour CT /MRI scans using the European Cooperative Acute Stroke Study criteria for hemorrhagic infarct (HI) or parenchymal hematoma (PH) and judged symptomatic by the treating neurologist as per Safe Implementation of Thrombolysis in Stroke criteria. There were 206 patients treated with IV tPA (mean age: 71.0 years range: 24-92 years), of whom 65/206 (32%) were aged ≥80 years. Overall, HT occurred in 41/206 patients (20%), HI in 31, PH1 in four (one symptomatic) and PH2 in six (three symptomatic). Age was not associated with HT (any HT: odds ratio [OR]=1.01 95% confidence interval [CI]=0.5-2.08 p=0.99 PH: OR=0.53 95% CI=0.12-2.3 p=0.51). There was one patient with PH1 and one patient with PH2 in 65 patients ≥80 years, both asymptomatic. LA was present in 112/208 (54%), and severe in 16.5%. LA increased with age (p<0.001) but was not associated with PH (any LA: OR=0.83 95% CI=0.25-2.8 p=0.99 severe LA: OR=0.54, 95% CI=0.09-3.5 p=0.99). Age ≥80 years or LA did not increase the risk of HT (including PH) after thrombolysis, although LA increased with age. Neither factor should exclude otherwise eligible patients from tPA treatment.
Publisher: MDPI AG
Date: 31-01-2022
DOI: 10.3390/APP12031560
Abstract: Stroke is the second most common cause of death and remains a persistent health challenge globally. Due to its highly time-sensitive nature, earlier stroke treatments should be enforced for improved patient outcome. The mobile stroke unit (MSU) was conceptualized and implemented to deliver the diagnosis and treatment to a stroke patient in the ultra-early time window ( h) in the pre-hospital setting and has shown to be clinically effective. However, due to geographical challenges, most rural communities are still unable to receive timely stroke intervention, as access to specialized stroke facilities for optimal stroke treatment poses a challenge. Therefore, the aircraft counterpart (Air-MSU) of the conventional road MSU offers a plausible solution to this shortcoming by expanding the catchment area for regional locations in Australia. The implementation of Air-MSU is currently hindered by several technical limitations, where current commercially available CT scanners are still oversized and too heavy to be integrated into a conventional helicopter emergency medical service (HEMS). In collaboration with the Australian Stroke Alliance and Melbourne Brain Centre, this article aims to explore the possibilities and methodologies in reducing the weight and, effectively, the size of an existing CT scanner, such that it can be retrofitted into the proposed search and rescue helicopter—Agusta Westland AW189. The result will be Australia’s first-ever customized CT scanner structure designed to fit in a search-and-rescue helicopter used for Air-MSU.
Publisher: SAGE Publications
Date: 19-01-2015
DOI: 10.1111/IJS.12412
Publisher: SAGE Publications
Date: 21-03-2018
Abstract: Several stroke outcome and quality control projects have demonstrated the success in stroke care quality improvement through structured process. However, Chinese health-care systems are challenged with its overwhelming numbers of patients, limited resources, and large regional disparities. To improve quality of stroke care to address regional disparities through process improvement. The Shanghai Stroke Service System (4S) is established as a regional network for stroke care quality improvement in the Shanghai metropolitan area. The 4S registry uses a web-based database that automatically extracts data from structured electronic medical records. Site-specific education and training program will be designed and administrated according to their baseline characteristics. Both acute reperfusion therapies including thrombectomy and thrombolysis in the acute phase and subsequent care were measured and monitored with feedback. Primary outcome is to evaluate the differences in quality metrics between baseline characteristics (including rate of thrombolysis in acute stroke and key performance indicators in secondary prevention) and post-intervention. The 4S system is a regional stroke network that monitors the ongoing stroke care quality in Shanghai. This project will provide the opportunity to evaluate the spectrum of acute stroke care and design quality improvement processes for better stroke care. A regional stroke network model for quality improvement will be explored and might be expanded to other large cities in China. www.clinicaltrials.gov . Unique identifier: NCT02735226.
Publisher: SAGE Publications
Date: 23-02-2021
Abstract: Admission stroke severity is an important clinical predictor of stroke outcomes. Pre-stroke physical activity contributes to stroke prevention and may also be associated with reduced stroke severity. Summarizing the evidence to date will inform strategies to reduce burden after stroke. To summarize the published evidence for the relationship between pre-stroke physical activity and admission stroke severity and to provide recommendations for future research. MEDLINE, Embase, Emcare, CENTRAL, and gray literature databases were searched on 14 February 2020 using search terms related to stroke and pre-stroke physical activity in adult stroke survivors. We screened 8,152 references and assessed 172 full-text references for eligibility. We included seven studies ( Pre-stroke physical activity may be associated with reduced admission stroke severity. Lack of randomized controlled trials limited causality conclusions. Future research recommendations were provided.
Publisher: MDPI AG
Date: 04-09-2021
DOI: 10.3390/DIAGNOSTICS11091621
Abstract: Final lesion volume (FLV) is a surrogate outcome measure in anterior circulation stroke (ACS). In posterior circulation stroke (PCS), this relation is plausibly understudied due to a lack of methods that automatically quantify FLV. The applicability of deep learning approaches to PCS is limited due to its lower incidence compared to ACS. We evaluated strategies to develop a convolutional neural network (CNN) for PCS lesion segmentation by using image data from both ACS and PCS patients. We included follow-up non-contrast computed tomography scans of 1018 patients with ACS and 107 patients with PCS. To assess whether an ACS lesion segmentation generalizes to PCS, a CNN was trained on ACS data (ACS-CNN). Second, to evaluate the performance of only including PCS patients, a CNN was trained on PCS data. Third, to evaluate the performance when combining the datasets, a CNN was trained on both datasets. Finally, to evaluate the performance of transfer learning, the ACS-CNN was fine-tuned using PCS patients. The transfer learning strategy outperformed the other strategies in volume agreement with an intra-class correlation of 0.88 (95% CI: 0.83–0.92) vs. 0.55 to 0.83 and a lesion detection rate of 87% vs. 41–77 for the other strategies. Hence, transfer learning improved the FLV quantification and detection rate of PCS lesions compared to the other strategies.
Publisher: SAGE Publications
Date: 26-08-2013
DOI: 10.1111/IJS.12132
Abstract: No evidence-based acute therapies exist for intracerebral hemorrhage. Intracerebral hemorrhage growth is an important determinant of patient outcome. Tranexamic acid is known to reduce hemorrhage in other conditions. The study aims to test the hypothesis that intracerebral hemorrhage patients selected with computed tomography angiography contrast extravasation ‘spot sign’ will have lower rates of hematoma growth when treated with intravenous tranexamic acid within 4·5-hours of stroke onset compared with placebo. The Spot sign and Tranexamic acid On Preventing ICH growth – AUStralasia Trial is a multicenter, prospective, 1:1 randomized, double-blind, placebo-controlled, investigator-initiated, academic Phase II trial. Intracerebral hemorrhage patients fulfilling clinical criteria (e.g. Glasgow Coma Scale , intracerebral hemorrhage volume ml, no identified secondary cause of intracerebral hemorrhage, no thrombotic events within the previous 12 months, no planned surgery) and demonstrating contrast extravasation on computed tomography angiography will receive either intravenous tranexamic acid 1 g 10-min bolus followed by 1 g eight-hour infusion or placebo. A second computed tomography will be performed at 24 ± 3 hours to evaluate intracerebral hemorrhage growth and patients followed up for three-months. The primary outcome measure is presence of intracerebral hemorrhage growth by 24 ± 3 hours, defined as either % or ml increase from baseline, and will be adjusted for baseline intracerebral hemorrhage volume. Secondary outcome measures include growth as a continuous measure, thromboembolic events, and the three-month modified Rankin Scale score. This is the first trial to evaluate the efficacy of tranexamic acid in intracerebral hemorrhage patients selected based on an imaging biomarker of high likelihood of hematoma growth. The trial is registered as NCT01702636.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2011
DOI: 10.1161/STROKEAHA.111.613653
Abstract: Central retinal artery occlusion is caused by a platelet-fibrin thrombus or embolic occlusion and is a stroke of the eye. Observational studies suggest that thrombolytics may restore ocular perfusion and visual function. We hypothesized that intravenous tissue-type plasminogen activator (tPA) administered within 24 hours of symptom onset might restore ocular perfusion and visual function. A placebo-controlled, randomized trial of intravenous tPA versus intravenous saline was performed in patients with clinically defined central retinal artery occlusion within 24 hours of symptom onset. tPA was administered at a total dose of 0.9 mg/kg, with 10% given as a 1-minute bolus and the remainder over 1 hour. An improvement of visual acuity of 3 lines or more was considered significant. Twenty-five percent (2 of 8) of the tPA group experienced the primary outcome at 1 week after tPA versus none of the placebo group. One patient had an intracranial hemorrhage. The visual acuity improvement of these 2 patients was not sustained at 6 months. In both patients, tPA was administered within 6 hours of symptom onset. Although essentially a negative study, it does add to the evidence base of reperfusion in central retinal artery occlusion by showing that the time window for intervention is likely to be hours. Reocclusion is a potential problem and may require adjuvant anticoagulation. Future studies should concentrate on determining the efficacy of thrombolytics in the -hour time window. URL: www.anzctr.org.au . Unique identifier: 83102.
Publisher: Wiley
Date: 26-02-2013
DOI: 10.1002/ANA.23837
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2013
DOI: 10.1161/STROKEAHA.113.002396
Abstract: Intracerebral hemorrhage is a serious potential complication of stroke thrombolysis. We investigated the optimal computed tomography perfusion (CTP) parameter to predict cerebral parenchymal hematoma (PH) in acute ischemic stroke. Patients with hyperacute ischemic stroke had whole-brain CTP and follow-up computed tomography/MRI to identify hemorrhagic transformation. The association of the 3 parameters relative cerebral blood flow, relative cerebral blood volume, and time to maximum ( T max ) with PH was examined using receiver operating characteristic analysis and multivariate logistic regression. Of 132 patients, 70 were treated with thrombolysis, and 14 (10.6%) developed PH on follow-up imaging. Baseline National Institutes of Health Stroke Scale score ( P =0.033) and thrombolysis ( P =0.003) were both predictive of PH. Receiver operating characteristic analysis revealed that T max s (area under the curve=0.748 P =0.002) and relative cerebral blood flow % of contralateral mean (area under the curve=0.689, P =0.021) were the optimal thresholds, and the Bayesian information criterion (+2.6) indicated that T max was more strongly associated with PH than relative cerebral blood flow. T max s volumes of mL allowed prediction of PH with sensitivity of 79%, specificity of 68%, and negative likelihood ratio of 3.16. T max s volume and thrombolysis were both independently predictive of PH in a multivariate logistic regression model ( P .05). T max s was the CTP parameter most strongly associated with PH. This outperformed relative cerebral blood flow %, which closely equates to CTP estimates of ischemic core volume. Although ischemic core volume on CTP is useful in the pretreatment prediction of PH, severe hypoperfusion on T max is more strongly associated and may allow better prediction of the likely anatomic location of hemorrhage.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2010
DOI: 10.1161/STROKEAHA.109.562116
Abstract: Background and Purpose— Currently, diffusion-weighted imaging (DWI) lesion volume is the most useful magnetic resonance imaging predictor of hemorrhagic transformation (HT). Preliminary studies have suggested that very low cerebral blood volume (VLCBV) predicts HT. We compared HT prediction by VLCBV and DWI using data from the EPITHET study. Methods— Normal-percentile CBV values were calculated from the nonstroke hemisphere. Whole-brain masks with CBV thresholds of the , 2.5, 5, and 10th percentiles were created. The volume of tissue with VLCBV was calculated within the acute DWI ischemic lesion. HT was graded as per ECASS criteria. Results— HT occurred in 44 of 91 patients. Parenchymal hematoma (PH) occurred in 13 (4 symptomatic) and asymptomatic hemorrhagic infarction (HI) in 31. The median volume of VLCBV was significantly higher in cases with PH. VLCBV predicted HT better than DWI lesion volume and thresholded apparent diffusion coefficient lesion volume in receiver operating characteristic analysis and logistic regression. A cutpoint at 2 mL VLCBV with the .5th percentile had 100% sensitivity for PH and, in patients treated with tissue plasminogen activator, defined a population with a 43% risk of PH (95% CI, 23% to 66%, likelihood ratio=16). VLCBV remained an independent predictor of PH in multivariate analysis with traditional clinical risk factors for HT. Conclusions— VLCBV predicted HT after thrombolysis better than did DWI or apparent diffusion coefficient volume in this large patient cohort. The advantage was greatest in patients with smaller DWI volumes. Prediction was better in patients who recanalized. If validated in an independent cohort, the addition of VLCBV to prethrombolysis decision making may reduce the incidence of HT.
Publisher: American Society of Neuroradiology (ASNR)
Date: 16-03-2017
DOI: 10.3174/AJNR.A5135
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2021
DOI: 10.1161/STROKEAHA.120.033246
Abstract: Whether reperfusion into infarcted tissue exacerbates cerebral edema has treatment implications in patients presenting with extensive irreversible injury. We investigated the effects of endovascular thrombectomy and reperfusion on cerebral edema in patients presenting with radiological evidence of large hemispheric infarction at baseline. In a systematic review and in idual patient-level meta-analysis of 7 randomized controlled trials comparing thrombectomy versus medical therapy in anterior circulation ischemic stroke published between January 1, 2010, and May 31, 2017 (Highly Effective Reperfusion Using Multiple Endovascular Devices collaboration), we analyzed the association between thrombectomy and reperfusion with maximal midline shift (MLS) on follow-up imaging as a measure of the space-occupying effect of cerebral edema in patients with large hemispheric infarction on pretreatment imaging, defined as diffusion-magnetic resonance imaging or computed tomography (CT)-perfusion ischemic core 80 to 300 mL or noncontrast CT-Alberta Stroke Program Early CT Score ≤5. Risk of bias was assessed using the Cochrane tool. Among 1764 patients, 177 presented with large hemispheric infarction. Thrombectomy and reperfusion were associated with functional improvement (thrombectomy common odds ratio =2.30 [95% CI, 1.32–4.00] reperfusion common odds ratio =4.73 [95% CI, 1.66–13.52]) but not MLS (thrombectomy β=−0.27 [95% CI, −1.52 to 0.98] reperfusion β=−0.78 [95% CI, −3.07 to 1.50]) when adjusting for age, National Institutes of Health Stroke Score, glucose, and time-to-follow-up imaging. In an exploratory analysis of patients presenting with core volume mL or CT-Alberta Stroke Program Early CT Score ≤3 (n=76), thrombectomy was associated with greater MLS after adjusting for age and National Institutes of Health Stroke Score (β=2.76 [95% CI, 0.33–5.20]) but not functional improvement (odds ratio, 1.71 [95% CI, 0.24–12.08]). In patients presenting with large hemispheric infarction, thrombectomy and reperfusion were not associated with MLS, except in the subgroup with very large core volume ( mL) in whom thrombectomy was associated with increased MLS due to space-occupying ischemic edema. Mitigating cerebral edema-mediated secondary injury in patients with very large infarcts may further improve outcomes after reperfusion therapies.
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: BMJ
Date: 22-01-2023
Abstract: Surgical treatment of intracerebral hemorrhage (ICH) is unproven, although meta-analyses suggest that both early conventional surgery with craniotomy and minimally invasive surgery (MIS) may be beneficial. We aimed to demonstrate the safety, feasibility, and promise of efficacy of early MIS for ICH using the Aurora Surgiscope and Evacuator. We performed a prospective, single arm, phase IIa Simon’s two stage design study at two stroke centers (10 patients with supratentorial ICH volumes ≥20 mL and National Institutes of Health Stroke Scale (NIHSS) score of ≥6, and surgery commencing hours after onset). Positive outcome was defined as ≥50% 24 hour ICH volume reduction, with the safety outcome lack of significant ICH reaccumulation. From December 2019 to July 2020, we enrolled 10 patients at two Australian Comprehensive Stroke Centers, median age 70 years (IQR 65–74), NIHSS score 19 (IQR 19–29), ICH volume 59 mL (IQR 25–77), at a median of 227 min (IQR 175–377) post-onset. MIS was commenced at a median time of 531 min (IQR 437–628) post-onset, had a median duration of 98 min (IQR 77–110), with a median immediate postoperative hematoma evacuation of 70% (IQR 67–80%). A positive outcome was achieved in 5/5 first stage patients and in 4/5 second stage patients. One patient developed significant 24 hour ICH reaccumulation otherwise, 24 hour stability was observed (median reduction 71% (IQR 61–80), 5/9 patients mL residual). Three patients died, unrelated to surgery. There were no surgical safety concerns. At 6 months, the median modified Rankin Scale score was 4 (IQR 3–6) with 30% achieving a score of 0–3. In this study, early ICH MIS using the Aurora Surgiscope and Evacuator appeared to be feasible and safe, warranting further exploration. ACTRN12619001748101.
Publisher: Springer International Publishing
Date: 2020
Publisher: Wiley
Date: 07-01-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2023
DOI: 10.1161/STROKEAHA.122.041260
Abstract: Several methods for conducting power analysis of studies with outcomes across the full ordinal modified Rankin Scale are proposed in the literature. No systematic comparison of accuracy, agreement, and sensitivity to small changes in hypothesized effect sizes for these methods is available. Our aim is to conduct such a systematic comparative analysis and to introduce a comprehensive freely available online tool to facilitate appropriate power analyses for ordinal outcomes. We performed simulation studies utilizing the control arm modified Rankin Scale distributions from the AVERT (A Very Early Rehabilitation Trial), EXTEND (Extending the Time for Thrombolysis in Emergency Neurological Deficits), and HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) studies, as well as a uniform distribution, in combination with hypothetical treatment effects. We systematically evaluated published power formulas for Ordinal Logistic Regression and Tournament Methods (generalized odds ratio Win Probability Win Ratio and Wilcoxon-Mann-Whitney U test). We also developed an online and downloadable Shiny R app facilitating s le size calculation for, and ordinal analysis of, modified Rankin Scale data. Power formulas for Tournament Methods performed well, while the formula for ordinal logistic regression was inaccurate. Tang’s Wilcoxon-Mann-Whitney U test s le size formula exhibited the highest accuracy. All methods, including ordinal logistic regression, had almost identical empirical power for a given s le size. All power methods exhibited sensitivity to small changes in hypothesized effect size. The developed freely available online app supports analytical and visualization requirements for all investigated methods for power and statistical analyses of ordinal modified Rankin Scale outcomes. As Tournament Method s le size formulas are assumption-free and accurately calculate power, stroke researchers should use these methods when designing studies with outcomes measured on the full or partially collapsed modified Rankin Scale as well as other ordinal scales, even if they intend to use ordinal logistic regression for analysis. Conducting sensitivity analyses of the effect size assumptions are essential for appropriate s le size estimation. Our developed tool supports both of these recommendations ( www.thembc.com.au/tournamentmethods ).
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.REHAB.2021.101487
Abstract: To enable development of effective interventions, there is a need to complete systematic early-phase dose articulation research. This scoping review aimed to synthesize dose articulation research of behavioral motor interventions for stroke recovery. MEDLINE and EMBASE were systematically searched for dose articulation studies. Preclinical experiments and adult clinical trials were classified based on the discovery pipeline and analyzed to determine which dose dimensions were articulated (time, scheduling or intensity) and how they were investigated (unidimensional vs multidimensional approach). Reporting of dose, safety and efficacy outcomes were summarized. The intervention description, risk of bias, and quality was appraised. We included 41 studies: 3 of preclinical dose preparation (93 rodents), 2 Phase I dose ranging (21 participants), 9 Phase IIA dose screening (198 participants), and 27 Phase IIB dose finding (1879 participants). All studies adopted a unidimensional approach. Time was the most frequent dimension investigated (53%), followed by intensity (29%), and scheduling (18%). Overall, 95% studies reported an efficacy outcome however, only 65% reported dose and 45% reported safety. Across studies, 61% were at high risk of bias, and the average percentage reporting of intervention description and quality was 61% and 67%, respectively. This review highlights a need to undertake more high-quality, early-phase studies that systematically articulate intervention doses from a multidimensional perspective in the field of behavioral motor stroke recovery. To address this gap, we need to invest in adapting early phase trial designs, especially Phase I, to support multidimensional dose articulation.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-10-2022
DOI: 10.1212/WNL.0000000000201426
Abstract: Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020). We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1–6.9] p 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1–4.6] p 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4–5.8] p 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6–0.9] p = 0.49). Stroke was diagnosed in 1.3% [1.31–1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82–2.97], 5,656/195,539) of all stroke hospitalizations. There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year. This study is registered under NCT04934020 .
Publisher: SAGE Publications
Date: 19-07-2012
DOI: 10.1111/J.1747-4949.2012.00787.X
Abstract: The appropriateness of a software platform for rapid MRI assessment of the amount of salvageable brain tissue after stroke is critical for both the validity of the Extending the Time for Thrombolysis in Emergency Neurological Deficits (EXTEND) Clinical Trial of stroke thrombolysis beyond 4.5 hours and for stroke patient care outcomes. The objective of this research is to develop and implement a methodology for selecting the acute stroke imaging software platform most appropriate for the setting of a multi-centre clinical trial. A multi-disciplinary decision making panel formulated the set of preferentially independent evaluation attributes. Alternative Multi-Attribute Value Measurement methods were used to identify the best imaging software platform followed by sensitivity analysis to ensure the validity and robustness of the proposed solution. Four alternative imaging software platforms were identified. RApid processing of Perfusion and Diffusion (RAPID) software was selected as the most appropriate for the needs of the EXTEND trial. A theoretically grounded generic multi-attribute selection methodology for imaging software was developed and implemented. The developed methodology assured both a high quality decision outcome and a rational and transparent decision process. This development contributes to stroke literature in the area of comprehensive evaluation of MRI clinical software. At the time of evaluation, RAPID software presented the most appropriate imaging software platform for use in the EXTEND clinical trial. The proposed multi-attribute imaging software evaluation methodology is based on sound theoretical foundations of multiple criteria decision analysis and can be successfully used for choosing the most appropriate imaging software while ensuring both robust decision process and outcomes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-11-2020
DOI: 10.1212/WNL.0000000000011212
Abstract: To describe sex differences in the presentation, diagnosis, and revision of diagnosis after early brain MRI in patients who present with acute transient or minor neurologic events. We performed a secondary analysis of a prospective multicenter cohort study of patients referred to neurology between 2010 and 2016 with a possible cerebrovascular event and evaluated with brain MRI within 8 days of symptom onset. Investigators documented the characteristics of the event, initial diagnosis, and final diagnosis. We used multivariable logistic regression analyses to evaluate the association between sex and outcomes. Among 1,028 patients (51% women, median age 63 years), more women than men reported headaches and fewer reported chest pain, but there were no sex differences in other accompanying symptoms. Women were more likely than men to be initially diagnosed with stroke mimic (54% of women vs 42% of men, adjusted odds ratio (OR) 1.60, 95% confidence interval [CI] 1.24–2.07), and women were overall less likely to have ischemia on MRI (10% vs 17%, OR 0.52, 95% CI 0.36–0.76). Among 496 patients initially diagnosed with mimic, women were less likely than men to have their diagnosis revised to minor stroke or TIA (13% vs 20%, OR 0.53, 95% CI 0.32–0.88) but were equally likely to have acute ischemia on MRI (5% vs 8%, OR 0.56, 95% CI 0.26–1.21). Stroke mimic was more frequently diagnosed in women than men, but diagnostic revisions were common in both. Early brain MRI is a useful addition to clinical evaluation in diagnosing transient or minor neurologic events.
Publisher: Wiley
Date: 03-12-2021
DOI: 10.1002/ANA.26272
Abstract: Perfusion imaging identifies anterior circulation stroke patients who respond favorably to endovascular thrombectomy (ET), but its role in basilar artery occlusion (BAO) is unknown. We hypothesized that BAO patients with limited regions of severe hypoperfusion (time to reach maximum concentration in seconds [Tmax] 10) would have a favorable response to ET compared to patients with more extensive regions involved. We performed a multicenter retrospective cohort study of BAO patients with perfusion imaging prior to ET. We prespecified a Critical Area Perfusion Score (CAPS 0–6 points), which quantified severe hypoperfusion (Tmax 10) in cerebellum (1 point/hemisphere), pons (2 points), and midbrain and/or thalamus (2 points). Patients were dichotomized into favorable (CAPS ≤ 3) and unfavorable (CAPS 3) groups. The primary outcome was a favorable functional outcome 90 days after ET (modified Rankin Scale = 0–3). One hundred three patients were included. CAPS ≤ 3 patients (87%) had a lower median National Institutes of Health Stroke Scale score (NIHSS 12.5, interquartile range [IQR] = 7–22) compared to CAPS 3 patients (13% 23, IQR = 19–36 p = 0.01). Reperfusion was achieved in 84% of all patients, with no difference between CAPS groups ( p = 0.42). Sixty‐four percent of reperfused CAPS ≤ 3 patients had a favorable outcome compared to 8% of nonreperfused CAPS ≤ 3 patients (odds ratio [OR] = 21.0, 95% confidence interval [CI] = 2.6–170 p 0.001). No CAPS 3 patients had a favorable outcome, regardless of reperfusion. In a multivariate regression analysis, CAPS ≤ 3 was a robust independent predictor of favorable outcome after adjustment for reperfusion, age, and pre‐ET NIHSS (OR = 39.25, 95% CI = 1.34– , p = 0.04). BAO patients with limited regions of severe hypoperfusion had a favorable response to reperfusion following ET. However, patients with more extensive regions of hypoperfusion in critical brain regions did not benefit from endovascular reperfusion. ANN NEUROL 2022 :23–32
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2022
DOI: 10.1161/STROKEAHA.121.038364
Abstract: Recent reports raise the possibility of cerebral amyloid angiopathy (CAA) leading to intracerebral hemorrhage in young adults following childhood neurosurgery, suggesting transmission of amyloid-β (Aβ) through neurosurgical procedures including dura mater grafting. Parenchymal Aβ deposition, and to a lesser extent tau aggregation, similar to that seen in Alzheimer disease, have also been described. We conducted a database review of 634 consecutive intracerebral hemorrhage patients aged years at a tertiary stroke center over 20 years to identify such patients. We identified 3 patients aged in their thirties who presented with spontaneous lobar intracerebral hemorrhage, with imaging or neuropathology consistent with CAA, and a history of childhood neurosurgery. Two of these patients had undergone a dural repair using cadaveric dura mater (Lyodura). In addition to CAA, both patients had neuropathologically confirmed parenchymal Aβ and tau deposits, characteristic of Alzheimer disease. Our findings support the concept of neurosurgical Aβ transmission but suggest that such cases are rare in standard clinical practice.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Springer International Publishing
Date: 2020
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: 17-07-2014
DOI: 10.1111/IJS.12302
Abstract: We are entering a challenging but exciting period when many new interventions may appear for stroke based on the use of devices. Hopefully these will lead to improved outcomes at a cost that can be afforded in most parts of the world. Nevertheless, it is vital that lessons are learnt from failures in the development of pharmacological interventions (and from some early device studies), including inadequate preclinical testing, suboptimal trial design and analysis, and underpowered studies. The device industry is far more disparate than that seen for pharmaceuticals companies are very variable in size and experience in stroke, and are developing interventions across a wide range of stroke treatment and prevention. It is vital that companies work together where sales and marketing are not involved, including in understanding basic stroke mechanisms, prospective systematic reviews, and education of physicians. Where possible, industry and academics should also work closely together to ensure trials are designed to be relevant to patient care and outcomes. Additionally, regulation of the device industry lags behind that for pharmaceuticals, and it is critical that new interventions are shown to be safe and effective rather than just feasible. Phase IV postmarketing surveillance studies will also be needed to ensure that devices are safe when used in the ‘real-world’ and to pick up uncommon adverse events.
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: Wiley
Date: 13-02-2023
DOI: 10.1111/JON.13084
Abstract: Two early basilar artery occlusion (BAO) randomized controlled trials did not establish the superiority of endovascular thrombectomy (EVT) over medical management. While many providers continue to recommend EVT for acute BAO, perceptions of equipoise in randomizing patients with BAO to EVT versus medical management may differ between clinician specialties. We conducted an international survey (January 18, 2022 to March 31, 2022) regarding management strategies in acute BAO prior to the announcement of two trials indicating the superiority of EVT, and compared responses between interventionalists (INTs) and non‐interventionalists (nINTs). Selection practices for routine EVT and perceptions of equipoise regarding randomizing to medical management based on neuroimaging and clinical features were compared between the two groups using descriptive statistics. Among the 1245 respondents (nINTs = 702), INTs more commonly believed that EVT was superior to medical management in acute BAO (98.5% vs. 95.1%, p .01). A similar proportion of INTs and nINTs responded that they would not randomize a patient with BAO to EVT (29.4% vs. 26.7%), or that they would only under specific clinical circumstances ( p = .45). Among respondents who would recommend EVT for BAO, there was no difference in the maximum prestroke disability, minimum stroke severity, or infarct burden on computed tomography between the two groups ( p .05), although nINTs more commonly preferred perfusion imaging (24.2% vs. 19.7%, p = .04). Among respondents who indicated they would randomize to medical management, INTs were more likely to randomize when the National Institutes of Health Stroke Scale was ≥10 (15.9% vs. 6.9%, p .01). Following the publication of two neutral clinical trials in BAO EVT, most stroke providers believed EVT to be superior to medical management in carefully selected patients, with most indicating they would not randomize a BAO patient to medical treatment. There were small differences in preference for advanced neuroimaging for patient selection, although these preferences were unsupported by clinical trial data at the time of the survey.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2022
DOI: 10.1161/STROKEAHA.122.036929
Abstract: Intravenous thrombolytics and endovascular thrombectomy for ischemic stroke have evolved in parallel. However, the best approach to combine these reperfusion therapies in patients eligible for both strategies remains uncertain. Initial randomized trials of endovascular thrombectomy included administration of intravenous thrombolytics to all eligible patients. However, whether that is of net benefit has been questioned and parallels drawn with treatment of ST-segment–elevation myocardial infarction, where intravenous thrombolytics are only given if first medical contact to percutaneous intervention is expected to be minutes. Six randomized trials of a direct thrombectomy approach versus intravenous thrombolytics followed by endovascular thrombectomy have now reported their results. With exception of a minority of patients in one trial, the trials all used alteplase rather than potentially more effective tenecteplase. This review examines the current state of evidence and implications for clinical practice. Importantly, these trials only apply to patients who present to a hospital with immediate access to endovascular thrombectomy and are not relevant to patients who receive thrombolytic and are then transferred to an endovascular-capable hospital. Although 2 of the 6 randomized trials met their prespecified noninferiority margin, these margins were large compared with the absolute benefit of alteplase. Overall, functional outcome was similar, with slight trends favoring bridging thrombolytics and a significant increase in final reperfusion. Symptomatic hemorrhage was increased by ≈1.8% in the bridging group but death was nonsignificantly lower. The workflow in direct thrombectomy trials involved delaying thrombolytic administration until eligibility for thrombectomy and the trials was established and randomization completed. This reduced the time available for thrombolytics to occur prethrombectomy compared with standard practice. We conclude that, pending in idual-patient data meta-analyses, intravenous thrombolytics retain an important role alongside endovascular thrombectomy. Further efforts to accelerate and enhance reperfusion with thrombolytics and perform in idual patient-level pooled subgroup analyses are warranted.
Publisher: Massachusetts Medical Society
Date: 09-05-2019
Publisher: Informa UK Limited
Date: 06-02-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2021
DOI: 10.1161/STROKEAHA.120.030661
Abstract: Distal clot migration is a recognized event following intravenous thrombolysis (IVT) in the setting of acute ischemic stroke. Of note, clots that were initially retrievable by endovascular thrombectomy may migrate to a distal nonretrievable location and compromise clinical outcome. We investigated the incidence of clot migration leading to clot inaccessibility following IVT in the time window of 4.5 to 9 hours. We performed a retrospective analysis of the EXTEND trial (Extending the Time for Thrombolysis in Emergency Neurological Deficits) data. Baseline and 12- to 24-hour follow-up clot location was determined on computed tomography angiogram or magnetic resonance angiogram. The incidence of clot migration leading to a change from retrievable to nonretrievable location was identified and compared between the two treatment groups (IVT versus placebo). Two hundred twenty patients were assessed. Clot migration from a retrievable to nonretrievable location occurred in 37 patients: 21 patients (19.3%) in the placebo group and 16 patients (14.4%) in the IVT group. No significant difference was identified in the incidence of clot migration leading to inaccessibility between groups ( P =0.336). Our results did not show increased clot migration leading to clot inaccessibility in patients treated with IVT.
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: S. Karger AG
Date: 2015
DOI: 10.1159/000381105
Abstract: b i Background: /i /b Remote structural and functional changes have been previously described after stroke and may have an impact on clinical outcome. We aimed to use multimodal MRI to investigate contralesional subcortical structural and functional changes 3 months after anterior circulation ischemic stroke. b i Methods: /i /b Fifteen patients with acute ischemic stroke had multimodal MRI imaging (including high resolution structural T1-MPRAGE and resting state fMRI) within 1 week of onset and at 1 and 3 months. Seven healthy controls of similar age group were also imaged at a single time point. Contralesional subcortical structural volume was assessed using an automated segmentation algorithm in FMRIB's Integrated Registration and Segmentation Tool (FIRST). Functional connectivity changes were assessed using the intrinsic connectivity contrast (ICC), which was calculated using the functional connectivity toolbox for correlated and anticorrelated networks (Conn). b i Results: /i /b Contralesional thalamic volume in the stroke patients was significantly reduced at 3 months compared to baseline (median change -2.1%, interquartile range [IQR] -3.4-0.4, p = 0.047), with the predominant areas demonstrating atrophy geometrically appearing to be the superior and inferior surface. The difference in volume between the contralesional thalamus at baseline (mean 6.41 ml, standard deviation [SD] 0.6 ml) and the mean volume of the 2 thalami in controls (mean 7.22 ml, SD 1.1 ml) was not statistically significant. The degree of longitudinal thalamic atrophy in patients was correlated with baseline stroke severity with more severe strokes being associated with a greater degree of atrophy (Spearman's rho -0.54, p = 0.037). There was no significant difference between baseline contralesional thalamic ICC in patients and control thalamic ICC. However, in patients, there was a significant linear reduction in the mean ICC of the contralesional thalamus over the imaging time points (p = 0.041), indicating reduced connectivity to the remainder of the brain. b i Conclusions: /i /b These findings highlight the importance of remote brain areas, such as the contralesional thalamus, in stroke recovery. Similar methods have the potential to be used in the prediction of stroke outcome or as imaging biomarkers of stroke recovery.
Publisher: SAGE Publications
Date: 19-06-2023
DOI: 10.1177/17474930231182018
Abstract: Following reperfusion treatment in ischemic stroke, computed tomography (CT) imaging at 24 h is widely used to assess radiological outcomes. Even without visible hyperattenuation, occult angiographic contrast may persist in the brain and confound Hounsfield unit-based imaging metrics, such as net water uptake (NWU). We aimed to assess the presence and factors associated with retained contrast post-thrombectomy on 24-h imaging using dual-energy CT (DECT), and its impact on the accuracy of NWU as a measure of cerebral edema. Consecutive patients with anterior circulation large vessel occlusion who had post-thrombectomy DECT performed 24-h post-treatment from two thrombectomy stroke centers were retrospectively studied. NWU was calculated by interside comparison of HUs of the infarct lesion and its mirror homolog. Retained contrast was quantified by the difference in NWU values with and without adjustment for iodine. Patients with visible hyperdensities from hemorrhagic transformation or visible contrast retention and bilateral infarcts were excluded. Cerebral edema was measured by relative hemispheric volume (rHV) and midline shift (MLS). Of 125 patients analyzed (median age 71 (IQR = 61–80), baseline National Institutes of Health Stroke Scale (NIHSS) 16 (IQR = 9.75–21)), reperfusion (defined as extended-Thrombolysis-In-Cerebral-Infarction 2b–3) was achieved in 113 patients (90.4%). Iodine-subtracted NWU was significantly higher than unadjusted NWU (17.1% vs 10.8%, p 0.001). In multivariable median regression analysis, increased age (p = 0.024), number of passes (p = 0.006), final infarct volume (p = 0.023), and study site (p = 0.021) were independently associated with amount of retained contrast. Iodine-subtracted NWU correlated with rHV (rho = 0.154, p = 0.043) and MLS (rho = 0.165, p = 0.033) but unadjusted NWU did not (rHV rho = –0.035, p = 0.35 MLS rho = 0.035, p = 0.347). Angiographic iodine contrast is retained in brain parenchyma 24-h post-thrombectomy, even without visually obvious hyperdensities on CT, and significantly affects NWU measurements. Adjustment for retained iodine using DECT is required for accurate NWU measurements post-thrombectomy. Future quantitative studies analyzing CT after thrombectomy should consider occult contrast retention.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2014
DOI: 10.1161/STROKEAHA.113.003352
Abstract: Preclinical and retrospective clinical data indicate that glyburide, a selective inhibitor of sulfonylurea receptor 1-transient receptor potential melastatin 4, is effective in preventing edema and improving outcome after focal ischemia. We assessed the feasibility of recruiting and treating patients with severe stroke while obtaining preliminary information on the safety and tolerability of RP-1127 (glyburide for injection). We studied 10 patients with acute ischemic stroke, with baseline diffusion-weighted imaging lesion volumes of 82 to 210 cm 3 , whether treated with intravenous recombinant tissue-type plasminogen activator, age 18 to 80 years, and time to RP-1127 ≤10 hours. Recruitment was completed within 10 months. The mean age was 50.5 years, and baseline diffusion-weighted image lesion volume was 102±23 cm 3 . There were no serious adverse events related to drug and no symptomatic hypoglycemia. The increase in ipsilateral hemisphere volume was 50±33 cm 3 . The proportion of 90-day modified Rankin Scale ≤4 was 90% (40% modified Rankin Scale, ≤3). RP-1127 at a dose of 3 mg/d was well tolerated and did not require any dose reductions. A clinical trial of RP-1127 is feasible. URL: www.clinicaltrials.gov . Unique identifier: NCT01268683.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2014
DOI: 10.1161/STROKEAHA.114.006884
Abstract: In malignant infarction, brain edema leads to secondary neurological deterioration and poor outcome. We sought to determine whether swelling is associated with outcome in smaller volume strokes. Two research cohorts of acute stroke subjects with serial brain MRI were analyzed. The categorical presence of swelling and infarct growth was assessed on diffusion-weighted imaging (DWI) by comparing baseline and follow-up scans. The increase in stroke volume (ΔDWI) was then sub ided into swelling and infarct growth volumes using region-of-interest analysis. The relationship of these imaging markers with outcome was evaluated in univariable and multivariable regression. The presence of swelling independently predicted worse outcome after adjustment for age, National Institutes of Health Stroke Scale, admission glucose, and baseline DWI volume (odds ratio, 4.55 95% confidence interval, 1.21–18.9 P .02). Volumetric analysis confirmed that ΔDWI was associated with outcome (odds ratio, 4.29 95% confidence interval, 2.00–11.5 P .001). After partitioning ΔDWI into swelling and infarct growth volumetrically, swelling remained an independent predictor of poor outcome (odds ratio, 1.09 95% confidence interval, 1.03–1.17 P .005). Larger infarct growth was also associated with poor outcome (odds ratio, 7.05 95% confidence interval, 1.04–143 P .045), although small infarct growth was not. The severity of cytotoxic injury measured on apparent diffusion coefficient maps was associated with swelling, whereas the perfusion deficit volume was associated with infarct growth. Swelling and infarct growth each contribute to total stroke lesion growth in the days after stroke. Swelling is an independent predictor of poor outcome, with a brain swelling volume of ≥11 mL identified as the threshold with greatest sensitivity and specificity for predicting poor outcome.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2022
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-08-2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2022
DOI: 10.1161/STROKEAHA.121.036104
Abstract: Factors contributing to cerebral edema in the post-hyperacute period of ischemic stroke (first 24–72 hours) are poorly understood. Blood-brain barrier (BBB) disruption and postischemic hyperperfusion reflect microvascular dysfunction and are associated with hemorrhagic transformation. We investigated the relationships between BBB integrity, cerebral blood flow, and space-occupying cerebral edema in patients who received acute reperfusion therapy. We performed a pooled analysis of patients treated for anterior circulation large vessel occlusion in the EXTEND-IA TNK and EXTEND-IA TNK part 2 trials who had MRI with dynamic susceptibility contrast-enhanced perfusion-weighted imaging 24 hours after treatment. We investigated the associations between BBB disruption and cerebral blood flow within the infarct with cerebral edema assessed using 2 metrics: first midline shift (MLS) trichotomized as an ordinal scale of negligible ( mm), mild (≥1 to mm), or severe (≥5 mm), and second relative hemispheric volume (rHV), defined as the ratio of the 3-dimensional volume of the ischemic hemisphere relative to the contralateral hemisphere. Of 238 patients analyzed, 133 (55.9%) had negligible, 93 (39.1%) mild, and 12 (5.0%) severe MLS at 24 hours. The associated median rHV was 1.01 (IQR, 1.00–1.028), 1.03 (IQR, 1.01–1.077), and 1.15 (IQR, 1.08–1.22), respectively. MLS and rHV were associated with poor functional outcome at 90 days ( P .002). Increased BBB permeability was independently associated with more edema after adjusting for age, occlusion location, reperfusion, parenchymal hematoma, and thrombolytic agent used (MLS cOR, 1.12 [95% CI, 1.03–1.20], P =0.005 rHV β, 0.39 [95% CI, 0.24–0.55], P .0001), as was reduced cerebral blood flow (MLS cOR, 0.25 [95% CI, 0.10–0.58], P =0.001 rHV β, −2.95 [95% CI, −4.61 to −11.29], P =0.0006). In subgroup analysis of patients with successful reperfusion (extended Treatment in Cerebral Ischemia 2b-3, n=200), reduced cerebral blood flow remained significantly associated with edema (MLS cOR, 0.37 [95% CI, 0.14–0.98], P =0.045 rHV β, −2.59 [95% CI, −4.32 to −0.86], P =0.004). BBB disruption and persistent hypoperfusion in the infarct after reperfusion treatment is associated with space-occupying cerebral edema. Further studies evaluating microvascular dysfunction during the post-hyperacute period as biomarkers of poststroke edema and potential therapeutic targets are warranted.
Publisher: Informa UK Limited
Date: 19-08-2016
DOI: 10.1080/14739879.2016.1219236
Abstract: A competency-based approach to family medicine (FM) post graduate (PG) training falls short of a holistic process if it focuses only on patients' needs without eliciting those of trainees. To identify perceived competency deficits of trainees and challenges hindering achievement of learning outcomes. PG FM programmes in sub-Saharan Africa. We conducted a cross-sectional survey using a web-based questionnaire with a list of competency items and challenges. Common Factor Analysis was used to ascertain which competency items and challenges accounted for the highest shared variability. A perceived competency deficit was assumed for any item with a component loading of <0.5. For challenges, higher component loadings denoted higher levels of agreement with the annotated item. Data were analysed using SPSS (version 16). A total of 150 trainees took the survey. Appraising and utilising scientific knowledge was the item with a perceived competency deficit, while poor mentor-mentee relationship was considered the foremost challenge that hindered learning outcomes. Critical appraisal and utilisation of scientific knowledge should be part of every stage of the African FM trainee's learning experience. To achieve this and other learning outcomes, improving mentor-mentee relationships are essential.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2023
DOI: 10.1161/STROKEAHA.121.038407
Abstract: The clinical and economic benefit of endovascular treatment (EVT) in addition to best medical management in patients with stroke with mild preexisting symptoms/disability is not well studied. We aimed to investigate cost-effectiveness of EVT in patients with large vessel occlusion and mild prestroke symptoms/disability, defined as a modified Rankin Scale score of 1 or 2. Data are from the HERMES collaboration (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials), which pooled patient-level data from 7 large, randomized EVT trials. We used a decision model consisting of a short-run model to analyze costs and functional outcomes within 90 days after the index stroke and a long-run Markov state transition model (cycle length of 12 months) to estimate expected lifetime costs and outcomes from a health care and a societal perspective. Incremental cost-effectiveness ratio and net monetary benefits were calculated, and a probabilistic sensitivity analysis was performed. EVT in addition to best medical management resulted in lifetime cost savings of $2821 (health care perspective) or $5378 (societal perspective) and an increment of 1.27 quality-adjusted life years compared with best medical management alone, indicating dominance of additional EVT as a treatment strategy. The net monetary benefits were higher for EVT in addition to best medical management compared with best medical management alone both at the higher (100 000$/quality-adjusted life years) and lower (50 000$/quality-adjusted life years) willingness to pay thresholds. Probabilistic sensitivity analysis showed decreased costs and an increase in quality-adjusted life years for additional EVT compared with best medical management only. From a health-economic standpoint, EVT in addition to best medical management should be the preferred strategy in patients with acute ischemic stroke with large vessel occlusion and mild prestroke symptoms/disability.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 14-08-2013
Publisher: Elsevier BV
Date: 09-2017
Publisher: Elsevier BV
Date: 05-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-04-2021
Publisher: SAGE Publications
Date: 04-11-2020
Abstract: Currently there are multiple variations of imaging-based patient selection mismatch methods in ischemic stroke. In the present study, we sought to compare the two most common mismatch methods and identify if there were different effects on the outcome of a randomized clinical trial depending on the mismatch method used. Investigate the effect of clinical and imaging-based mismatch criteria on patient outcomes of a pooled cohort from randomized trials of intravenous tenecteplase versus alteplase. Baseline clinical and imaging scores were used to categorize patients as meeting either the DAWN mismatch (baseline NIHSS ≥ 10, and age cut-offs for ischemic core volume) or DEFUSE 2 mismatch criteria (mismatch volume 15 mL, mismatch ratio 1.8 and ischemic core 70 mL). We then investigated whether tenecteplase-treated patients had favorable odds of less disability (on modified Rankin scale, mRS) compared to those treated with alteplase, for clinical and imaging mismatch, respectively. From 146 pooled patients, 71 received alteplase and 75 received tenecteplase. The overall pooled group did not show improved patient outcomes when treated with tenecteplase (mRS 0-1 OR 1.77, 95% CI 0.89–3.51, p = 0.102) compared with alteplase. A total of 39 (27%) patients met both clinical and imaging mismatch criteria, 25 (17%) patients met only imaging criteria, 36 (25%) met only clinical mismatch criteria and, finally, 46 (31%) did not meet either of imaging or mismatch criteria. Patients treated with tenecteplase had more favorable outcomes when they met either imaging mismatch (mRS 0–1, OR 2.33, 95% CI 1.13–5.94, p = 0.032) or clinical mismatch criteria (mRS 0–1, OR 2.15, 95% CI 1.142, 8.732, p = 0.027) but with differing proportions. Target mismatch selection was more inclusive and exhibited in a larger treatment effect between tenecteplase and alteplase.
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1SC03368A
Abstract: Electron delocalization in contorted polycyclic aromatic hydrocarbon (PAH) molecules was examined through 3D isotropic magnetic shielding (IMS) contour maps built around the molecules using pseudo-van der Waals surfaces.
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.JCLINEPI.2021.11.020
Abstract: Maintaining clinical guideline currency has been one challenge to traditional guideline development. This paper describes the methods used to maintain a large national guideline for stroke management. The Australian Stroke Clinical Guidelines are developed to meet Australian National Health and Medical Research Council (NHMRC) standards. Monthly surveillance is conducted for new systematic reviews and randomised controlled studies. Included studies undergo data extraction followed by preparation of updated evidence-to-decision frameworks which are used to inform updates, or development of new recommendations. Small writing groups made up of clinical experts and those with lived experience review and agree on changes, which are finally reviewed by a multidisciplinary Guidelines Steering Group. Draft changes are developed and published using the online MAGICapp platform, with dissemination and promotion via traditional methods as well as social media. Each month approximately 350 abstracts are considered, covering 96 clinical topics and taking on average 16 h to review. There have been four major guideline updates covering 34 new and updated recommendations. It is feasible to use 'living' methods to maintain the Australian Clinical Guidelines for Stroke Management. Further work is now needed to understand the impact of living guidelines.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-10-2022
Publisher: Elsevier BV
Date: 10-2021
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: 11-2020
DOI: 10.1161/STROKEAHA.120.030157
Abstract: In patients undergoing mechanical thrombectomy, achieving complete (Thrombolysis in Cerebral Infarction 3) rather than incomplete successful reperfusion (Thrombolysis in Cerebral Infarction 2b) is associated with better functional outcome. Despite technical improvements, incomplete reperfusion remains the final angiographic result in 40% of patients according to recent trials. As most incomplete reperfusions are caused by distal vessel occlusions, they are potentially amenable to rescue strategies. While observational data suggest a net benefit of up to 20% in functional independence of incomplete versus complete reperfusions, the net benefit of secondary improvement from Thrombolysis in Cerebral Infarction 2b to 3 reperfusion might differ due to lengthier procedures and delayed reperfusion. Current strategies to tackle distal vessel occlusions consist of distal (microcatheter) aspiration, small adjustable stent retrievers, and administration of intra-arterial thrombolytics. While there are promising reports evaluating those techniques, all available studies show relevant limitations in terms of selection bias, single-center design, or nonconsecutive patient inclusion. Besides an assessment of risks associated with rescue maneuvers, we advocate that the decision-making process should also include a consideration of potential outcomes if complete reperfusion would successfully be achieved. These include (1) a futile angiographic improvement (hypoperfused territory is already infarcted), (2) an unnecessary angiographic improvement (the patient would not have developed infarction if no rescue maneuver was performed), and (3) a successful rescue maneuver with clinical benefit. Currently there is paucity of data on how these scenarios can be predicted and the decision whether to treat or to stop in a patient with incomplete reperfusion involves many unknowns. To advance the status quo, we outline current knowledge gaps and avenues of potential research regarding this clinically important question.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 22-02-2022
DOI: 10.1212/WNL.0000000000013210
Abstract: The relevance of impaired microvascular tissue-level reperfusion despite complete upstream macrovascular angiographic reperfusion (no-reflow) in human stroke remains controversial. We investigated the prevalence and clinical-radiologic features of this phenomenon and its associations with outcomes in 3 international randomized controlled thrombectomy trials with prespecified follow-up perfusion imaging. In a pooled analysis of the Extending the Time for Thrombolysis in Emergency Neurological Deficits–Intra-Arterial (EXTEND-IA ClinicalTrials.gov NCT01492725), Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK NCT02388061), and Determining the Optimal Dose of Tenecteplase Before Endovascular Therapy for Ischaemic Stroke (EXTEND-IA TNK Part 2 NCT03340493) trials, patients undergoing thrombectomy with final angiographic expanded Treatment in Cerebral Infarction score of 2c to 3 score for anterior circulation large vessel occlusion and 24-hour follow-up CT or MRI perfusion imaging were included. No-reflow was defined as regions of visually demonstrable persistent hypoperfusion on relative cerebral blood volume or flow maps within the infarct and verified quantitatively by % asymmetry compared to a mirror homolog in the absence of carotid stenosis or reocclusion. Regions of no-reflow were identified in 33 of 130 patients (25.3%), encompassed a median of 60.2% (interquartile range 47.8%–70.7%) of the infarct volume, and involved both subcortical (n = 26 of 33, 78.8%) and cortical (n = 10 of 33, 30.3%) regions. Patients with no-reflow had a median 25.2% (interquartile range 16.4%–32.2%, p 0.00001) relative cerebral blood volume interside reduction and 19.1% (interquartile range 3.9%–28.3%, p = 0.00011) relative cerebral blood flow reduction but similar mean transit time (median −3.3%, interquartile range −11.9% to 24.4%, p = 0.24) within the infarcted region. Baseline characteristics were similar between patients with and those without no-reflow. The presence of no-reflow was associated with hemorrhagic transformation (adjusted odds ratio [aOR] 1.79, 95% confidence interval [CI] 2.32–15.57, p = 0.0002), greater infarct growth (β = 11.00, 95% CI 5.22–16.78, p = 0.00027), reduced NIH Stroke Scale score improvement at 24 hours (β = −4.06, 95% CI 6.78–1.34, p = 0.004) and being dependent or dead at 90 days as assessed by the modified Rankin Scale (aOR 3.72, 95% CI 1.35–10.20, p = 0.011) in multivariable analysis. Cerebral no-reflow in humans is common, can be detected by its characteristic perfusion imaging profile using readily available sequences in the clinical setting, and is associated with posttreatment complications and being dependent or dead. Further studies evaluating the role of no-reflow in secondary injury after angiographic reperfusion are warranted. This study provides Class II evidence that cerebral no-reflow on CT/MRI perfusion imaging at 24 hours is associated with posttreatment complications and poor 3-month functional outcome.
Publisher: Wiley
Date: 20-08-2012
DOI: 10.1111/J.1468-1331.2012.03841.X
Abstract: Absence of FLAIR hyperintensity within an acute infarct is associated with stroke onset <4.5 h. However, some patients rapidly develop FLAIR hyperintensity within this timeframe. We hypothesized that development of early infarct FLAIR hyperintensity would predict hemorrhagic transformation (HT) in patients treated with tissue plasminogen activator (tPA) < 4.5 h after onset. Consecutive acute stroke patients treated with intravenous tPA <4.5 h after onset who had MRI before and 1 day after thrombolysis were included. Two raters (blind to HT) independently identified FLAIR hyperintensity with reference to the diffusion-weighted image (DWI) lesion. HT was assessed using T2* MRI at 24 h. Hemorrhagic infarction (HI) was defined as petechial HT without mass effect, and parenchymal hematoma (PH) as HT with mass effect. Multivariable logistic regression analysis for HT included FLAIR status, baseline National Institutes of Health Stroke Scale and DWI lesion volume, leukoaraiosis (Wahlund score), serum glucose and reperfusion. Of 109 patients, 33 (30%) had acute FLAIR hyperintensity. HT occurred in 17 patients (15.6% 15 HI, 2 PH). HT was more common in FLAIR-positive patients than FLAIR-negative patients (33.3% vs. 9.2%, P = 0.009). Median time-to-scan and median time-to-thrombolysis did not differ significantly between patients with HT and without [97 IQR(68, 155) vs. 90 IQR(73, 119), P = 0.5 120 IQR(99, 185) vs. 125 IQR(95, 150), P = 0.6, respectively]. In multivariable analysis, only FLAIR hyperintensity was independently associated with HT after thrombolysis (OR 18 95% CI 2-175, P = 0.013). Early development of FLAIR hyperintensity within the area of diffusion restriction is associated with increased risk of HT after thrombolysis in acute stroke patients.
Publisher: American Society of Neuroradiology (ASNR)
Date: 12-12-2013
DOI: 10.3174/AJNR.A3733
Publisher: Cold Spring Harbor Laboratory
Date: 07-06-2023
DOI: 10.1101/2023.06.05.23291002
Abstract: Patients with large vessel occlusion (LVO) stroke of milder baseline clinical severity are often missed by pre-hospital severity-based triage tools. We examined whether these patients had differences in 1) markers of collateral circulation and 2) the relative harm of transfer delays on outcome, compared to patients with clinically more severe baseline deficits. Registry data from two large Australian thrombectomy centers was used to identify all directly presenting and transferred LVO patients undergoing endovascular thrombectomy, ided into those with milder baseline deficits (NIHSS ) and severe baseline deficits (NIHSS ≥10). Baseline CT-perfusion markers of collateral circulation and the association between transfer status and functional outcome (using the 90-day modified Rankin Scale) were compared. Of 1210 included LVO patients, 273 (22.6%) had milder severity. Milder LVO patients showed smaller median ischemic core volumes (12.6 [IQR 0.0-17.9] vs 27.5 [IQR 6.5-37.1] mL, p .001)), higher median perfusion mismatch ratio (148.3 [IQR 5.0-500.0] vs 66.2 [IQR 3.6-17.2], p .001) and lower median hypoperfusion intensity ratio (0.25 [IQR 0.18-0.38] vs 0.40 [IQR 0.22-0.57], p .001). Transferred patients had a lower odd of excellent outcome than primary presenters, when deficits were severe deficits (aOR 0.759 [95% CI 0.576-0.999]) but not when deficits were milder (aOR 1.357 [95% CI 0.764-2.409], pinteraction=0.122). Patients with LVO stroke of milder clinical severity have significantly better imaging markers of collateral circulation compared to high-severity patients. Despite high rates of thrombolytics, secondary transfer to thrombectomy-center was only associated with poorer 90-day functional outcomes in higher-severity patients. Failure of pre-hospital screening tools to detect lower-severity LVO patients for immediate pre-hospital bypass to a thrombectomy center may not deleteriously affect their outcome.
Publisher: Wiley
Date: 17-03-2022
DOI: 10.1002/ANA.26331
Abstract: The objective of this study was to evaluate functional and safety outcomes of endovascular thrombectomy (EVT) versus medical management (MM) in patients with M2 occlusion and examine their association with perfusion imaging mismatch and stroke severity. In a pooled, patient-level analysis of 3 randomized controlled trials (EXTEND-IA, EXTEND-and IA-TNK parts 1 and 2) and 2 prospective nonrandomized studies (INSPIRE and SELECT), we evaluated EVT association with 90-day functional independence (modified Rankin Scale [mRS] = 0-2) in isolated M2 occlusions as compared to medical management overall and in subgroups by mismatch profile status and stroke severity. We included 517 patients (EVT = 195 and MM = 322), baseline median (interquartile range [IQR]) National Institutes of Health Stroke Scale (NIHSS) was 13 (8-19) in EVT versus 10 (6-15) in MM, p < 0.001. Pretreatment ischemic core did not differ (EVT = 10 [0-24] ml vs MM = 9 [3-21] ml, p = 0.59). Compared to MM, EVT was more frequently associated with functional independence (68.3 vs 61.6%, adjusted odds ratio [aOR] = 2.42, 95% confidence interval [CI] = 1.25-4.67, p = 0.008, inverse probability of treatment weights [IPTW]-OR = 1.75, 95% CI = 1.00-3.75, p = 0.05) with a shift toward better mRS outcomes (adjusted cOR = 2.02, 95% CI:1.23-3.29, p = 0.005), and lower mortality (5 vs 10%, aOR = 0.32, 95% CI = 0.12-0.87, p = 0.025). EVT was associated with higher functional independence in patients with a perfusion mismatch profile (EVT = 70.7% vs MM = 61.3%, aOR = 2.29, 95% CI = 1.09-4.79, p = 0.029, IPTW-OR = 2.02, 1.08-3.78, p = 0.029), whereas no difference was found in those without mismatch (EVT = 43.8% vs MM = 62.7%, p = 0.17, IPTW-OR: 0.71, 95% CI = 0.18-2.78, p = 0.62). Functional independence was more frequent with EVT in patients with moderate or severe strokes, as defined by baseline NIHSS above any thresholds from 6 to 10, whereas there was no difference between groups with milder strokes below these thresholds. In patients with M2 occlusion, EVT was associated with improved clinical outcomes when compared to MM. This association was primarily observed in patients with a mismatch profile and those with higher stroke severity. ANN NEUROL 2022 :629-639.
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.JSTROKECEREBROVASDIS.2014.07.018
Abstract: Large vessel occlusion (LVO) is associated with poor functional outcome in acute ischemic stroke. Given the uncertainty whether LVO has the same significance in mild and severe stroke, we compared functional outcomes after intravenous thrombolysis, based on severity and LVO. Ischemic stroke patients were thrombolyzed in less than 4.5 hours after onset between 2007 and 2013. LVO was defined as occlusion of one of the following arteries: internal carotid, middle cerebral (M1/M2), anterior cerebral (A1), posterior cerebral (P1), basilar, or vertebral (V4) arteries on prethrombolysis computed tomography angiography. Mild stroke was defined as baseline National Institutes of Health Stroke Scale (NIHSS) score 0-6. Favorable outcome was defined as modified Rankin Scale (mRS) score 0-1 at 3 months or equal to the prestroke mRS. There were 175 acute stroke patients, median age 74 years (interquartile range [IQR], 64-83), median baseline NIHSS = 11 (IQR, 5-16), and 63 of 175 patients (36%) with mild stroke. LVO was associated with worse outcome in severe stroke (age-adjusted odds ratio [OR] of favorable outcome, .42 95% confidence interval [CI], .19-.93 P = .033) and mortality (age-adjusted OR, 3.52 95% CI, 1.08-11.48 P = .037). Although the difference in favorable outcome between mild stroke patients with and without LVO was not significant (55.6% vs. 74.1%, P = .262 age-adjusted OR of favorable outcome, .42 95% CI, .1-1.84 P = .251), the similarity of effects across both subgroups cannot be excluded (LVO-by-stroke severity interaction test, P = .906). LVO is associated with worse functional outcome and mortality in severe stroke after intravenous thrombolysis. Although significant association between LVO and outcome in mild stroke was not found, there were similar effects on outcome and a larger study might well confirm a relationship.
Publisher: SAGE Publications
Date: 05-01-2018
Abstract: Clinical practice guidelines are essential for driving evidence-based clinical care to patients. In an era of ever-increasing research evidence, keeping guidelines up to date is a challenging and resource-intensive process. Advances in technological platforms provide opportunities to develop new models of guideline development that will allow for continuous, rapid updates to recommendations as new evidence emerges. As Australia and other countries begin to develop these models, we have an opportunity to work more closely together to ensure the most efficient use of resources.
Publisher: Elsevier BV
Date: 09-2007
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2022
DOI: 10.1161/STROKEAHA.121.037770
Abstract: Observational studies have shown endovascular treatment (EVT) for acute ischemic stroke to be effective in the elderly, despite resulting in poorer outcomes and higher rates of mortality compared with younger patients. Randomized data on the effect of advanced age on outcomes following EVT are, however, lacking. Our aim was to assess the EVT effect for ischemic stroke in patients aged ≥85 years and the influence of age on outcome in a large, randomized trial dataset. Data were from the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration, a meta-analysis of 7 randomized trials published between January 1, 2010, and May 31, 2017, that tested the efficacy of EVT. A possible multiplicative interaction effect of age on the relationship between treatment and outcome was investigated. Ordinal logistic regression tested the association between EVT and 90-day functional outcome (modified Rankin Scale, primary outcome) in patients ≥85 years. Multivariable binary logistic regression was performed to compare primary and secondary outcomes (modified Rankin Scale score of 0–2/5–6) of patients ≥85 years versus those years. We included 1764 patients in the analysis, of whom 77 (4.4%) were ≥85 years old. A significant interaction of age and treatment on poor outcome (modified Rankin Scale score of 5–6, P =0.020) and mortality ( P =0.031) was observed, with older adults having worse functional outcomes at 90 days compared with younger patients (adjusted common odds ratio, 0.20 [95% CI, 0.13–0.33]). However, a benefit of EVT was observed in the ≥85-year-old patient subgroup (common odds ratio, 4.20 [95% CI, 1.56–11.32]). Age ≥85 years was not significantly associated with differing rates of symptomatic intracerebral hemorrhage or reperfusion (adjusted odds ratio, 1.92 [95% CI, 0.71–5.15] and adjusted odds ratio, 0.91 [95% CI, 0.40–2.06], respectively). Patients ≥85 years old with independent premorbid function more often achieve good functional outcomes and have lower rates of mortality when treated with EVT compared with conservative management, with an observed treatment effect modification of age on outcome. EVT should therefore not be withheld in this subgroup.
Publisher: SAGE Publications
Date: 21-11-2013
DOI: 10.1111/IJS.12209
Abstract: The currently proven time window for thrombolysis in ischemic stroke is 4·5 h. Beyond this, the risks and benefits of thrombolysis are uncertain. To determine whether thrombolysis and reperfusion were beneficial after 4·5 h, we examined clinical and radiological outcomes in patients treated with tissue plasminogen activator or placebo within 4·5–6 h, using data from the Echoplanar Imaging Thrombolytic Evaluation Trial. In the Echoplanar Imaging Thrombolytic Evaluation Trial, ischemic stroke patients presenting three to six-hours after stroke onset were randomized to tissue plasminogen activator or placebo, without knowledge of magnetic resonance imaging results. This analysis was restricted to patients treated between 4·5 and 6 h. The effect of tissue plasminogen activator and reperfusion on infarct growth between baseline diffusion-weighted imaging and day 90 T2 imaging was assessed, along with good neurological outcome (⩾8 point reduction or reaching 0–1 at 90 days on National Institutes of Health Stroke Scale) and functional outcome (modified Rankin scale). The effect of tissue plasminogen activator on reperfusion was also analyzed. Sixty-nine patients were treated 4·5–6 h after onset, and infarct growth was assessed in 63. Tissue plasminogen activator was associated with lower relative growth (94% vs. 168%, P = 0·03) and a trend to lower absolute growth (−0·17 ml versus 9·6 ml, P = 0·07). Reperfusion was increased in the tissue plasminogen activator group (58% versus 25%, P = 0·03) and was associated with increased rates of good neurological (86% versus 28% P 0·001) and functional (modified Rankin scale 0–2 73% versus 34%, P = 0·01) outcomes. Reperfusion was strongly associated with lower relative (80% versus 189%, P 0·001) and absolute (−2·5 ml versus 40 ml, P 0·001) infarct growth. Thrombolysis 4·5–6 h after stroke onset reduced infarct growth and increased the rate of reperfusion, which was associated with good neurological and functional outcome.
Publisher: SAGE Publications
Date: 11-03-2014
DOI: 10.1111/IJS.12203
Abstract: In acute ischemic stroke perfusion/diffusion-weighted image, mismatch using magnetic resonance imaging approximates the ischemic penumbra. For early time windows, mismatch salvage improves clinical outcomes, but uncertainty exists at later time epochs. We hypothesized that (a) mismatch may exist up to 48 h (b) the proportion of mismatch salvage is time independent and (c) when salvaged, it improves clinical outcomes. Magnetic resonance imaging was performed within 48 h of ischemic stroke. Perfusion-weighted image was defined by relative T max two-second delay. Perfusion/diffusion-weighted image mismatch was the perfusion-weighted image not overlapped by the diffusion-weighted image when coregistered. Infarct volume and disability (modified Rankin Score) were assessed at three-months. Mismatch salvage was the region not overlapped by final infarction. Favorable outcome was defined as modified Rankin Score 0–1. Sixty-six patients were studied [mean age 69·9 years (standard deviation 13·1), initial median National Institute of Health Stroke Scale 9·0 (interquartile range 6·0, 18·3)]. There was no relationship between time of stroke onset and the proportion of mismatch salvaged ( P = 0·73). Age (adjusted odds ratio = 0·92, 95% confidence interval 0·86–0·98, P = 0·01), initial National Institute of Health Stroke Scale (adjusted odds ratio = 0·80, 95% confidence interval 0·70–0·92, P 0·01), mismatch volume (adjusted odds ratio = 0·98, 95% confidence interval 0·968–0·1, P = 0·05), and percentage of mismatch salvage (adjusted odds ratio = 1·04, 95% confidence interval 0·99–1·07, P = 0·05) were independently associated with favorable outcome. Using coregistered perfusion/diffusion-weighted image criteria, mismatch persists up to 48 h post stroke. For the whole group, the proportion of mismatch salvage remains independent of time and, although the effect is small, its salvage is independently associated with improved clinical outcomes at three-months. Larger s le sizes are needed to determine the time limit for mismatch salvage.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-09-2020
DOI: 10.1212/WNL.0000000000010867
Abstract: To determine public health and cost consequences of time delays to endovascular thrombectomy (EVT) for patients, health care systems, and society, we estimated quality-adjusted life-years (QALYs) of EVT-treated patients and associated costs based on times to treatment. The Markov model analysis was performed from US health care and societal perspectives over a lifetime horizon. Contemporary data from 7 trials within the Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) collaboration served as data source. Aside from cumulative lifetime costs, we calculated the net monetary benefit (NMB) to determine the economic value of care. We used a contemporary willingness-to-pay threshold of $100,000 per QALY for NMB calculations. Every 10 minutes of earlier treatment resulted in an average gain of 39 days (95% prediction interval 23–53 days) of disability-free life. Overall, the cumulative lifetime costs for patients with earlier or later treatment were similar. Patients with later treatment had higher morbidity-related costs but over a shorter time span due to their shorter life expectancy, resulting in similar lifetime costs as in patients with early treatment. Regarding the economic value of care, every 10 minutes of earlier treatment increased the NMB by $10,593 (95% prediction interval $5,549–$14,847) and by $10,915 (95% prediction interval $5,928–$15,356) taking health care and societal perspectives, respectively. Any time delay to EVT reduces QALYs and decreases the economic value of care provided by this intervention. Health care policies to implement efficient prehospital triage and to accelerate in-hospital workflow are urgently needed.
Publisher: SAGE Publications
Date: 10-11-2013
DOI: 10.1111/IJS.12206
Abstract: Thrombolysis with tissue plasminogen activator is proven to reduce disability when given within 4.5 h of ischemic stroke onset. However, tissue plasminogen activator only succeeds in recanalizing large vessel arterial occlusion in a minority of patients. We hypothesized that anterior circulation ischemic stroke patients, selected with ‘dual target’ vessel occlusion and evidence of salvageable brain using computed tomography or magnetic resonance imaging ‘mismatch’ within 4.5 h of onset, would have improved reperfusion and early neurological improvement when treated with intra-arterial clot retrieval after intravenous tissue plasminogen activator compared with intravenous tissue plasminogen activator alone. EXTEND-IA is an investigator-initiated, phase II, multicenter prospective, randomized, open-label, blinded-endpoint study. Ischemic stroke patients receiving standard 0.9 mg/kg intravenous tissue plasminogen activator within 4.5 h of stroke onset who have good prestroke functional status (modified Rankin Scale , no upper age limit) will undergo multimodal computed tomography or magnetic resonance imaging. Patients who also meet dual target imaging criteria: vessel occlusion (internal carotid or middle cerebral artery) and mismatch (perfusion lesion: ischemic core mismatch ratio .2, absolute mismatch ml, ischemic core volume ml) will be randomized to either clot retrieval with the Solitaire FR device after full dose intravenous tissue plasminogen activator, or tissue plasminogen activator alone. The coprimary outcome measure will be reperfusion at 24 h and favorable clinical response (reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0–1) at day 3. Secondary outcomes include modified Rankin Scale at day 90, death, and symptomatic intracranial hemorrhage.
Publisher: American Chemical Society (ACS)
Date: 25-05-2022
Abstract: The BenzAI program can automatically generate benzenoids with defined structural constraints, like the number of hexagons, the number of carbon and/or hydrogen atoms, the existence of symmetries, the number of Kekulé structures, their diameter, or more elaborate criteria like their irregularity. BenzAI allows both automatic generation and manual building of benzenoids including or excluding defined patterns. For all benzenoids with less than 10 rings, it can extract IR spectra from a database that we generated. It computes local aromaticity for closed-shell and monoradical species using circuit-based algorithms. We present practical ex les of what can be done with BenzAI for a ersity of cases.
Publisher: Massachusetts Medical Society
Date: 20-06-2013
DOI: 10.1056/NEJMC1304759
Publisher: S. Karger AG
Date: 2013
DOI: 10.1159/000353670
Abstract: b i Background: /i /b CHADS sub /sub and CHA sub /sub DS sub /sub -VASc scores are validated tools for assessing stroke risk in patients with atrial fibrillation (AF). We investigated whether these scores are associated with 3-month stroke outcomes and evaluated the utility of these scores in stratifying 3-month stroke outcomes in both patients with and without AF. b i Methods: /i /b We analysed 6,612 acute ischaemic stroke patients from the Virtual International Stroke Trials Archive who received either placebo or ineffective active treatments not associated with significant cardiac complications. Outcomes included 3-month mortality, good functional outcomes defined as modified Rankin Scale score ≤1 and serious cardiac adverse events (SCAEs) defined as one of acute coronary syndrome, symptomatic heart failure, cardiopulmonary arrest, life-threatening arrhythmia and cardiac death. The association between the pre-stroke CHADS sub /sub and CHA sub /sub DS sub /sub -VASc scores and 3-month stroke outcomes was assessed using binary logistic regression. The utility of the two scores in estimating 3-month stroke outcomes was assessed using area under the receiver operator characteristic curves (AUC) and compared using the & #x03C7 sup /sup test. b i Results: /i /b In this cohort, 26.5% had AF, 35.3% received IV tissue plasminogen activator (tPA), 17.7% died, 25.1% achieved good functional outcomes and 9.5% had ≥1 SCAE at 3 months. High-risk (≥2) pre-stroke CHADS sub /sub and CHA sub /sub DS sub /sub -VASc scores are both associated with 3-month mortality (CHADS sub /sub : odds ratio, OR, 2.33, 95% confidence interval 1.81-3.00 CHA sub /sub DS sub /sub -VASc: OR 3.01, 2.00-4.80), good functional outcomes (CHADS sub /sub : OR 0.47, 0.39-0.57 CHA sub /sub DS sub /sub -VASc: OR 0.55, 0.42-0.71) and SCAEs (CHADS sub /sub : OR 1.76, 1.28-2.42 CHA sub /sub DS sub /sub -VASc: OR 2.69, 1.53-4.73) after adjusting for baseline differences in neurological impairment, tPA use and AF. The pre-stroke CHA sub /sub DS sub /sub -VASc score is better than the CHADS sub /sub score in estimating 3-month stroke outcomes in both patients with and without AF (p ≤ 0.005 in all AUC comparisons). High-risk pre-stroke CHA sub /sub DS sub /sub -VASc score has high sensitivity for mortality (AF: 0.96, 0.94-0.98 no AF: 0.88, 0.86-0.91) and negative predictive value for SCAE (AF: 0.93, 0.87-0.96 no AF: 0.96, 0.95-0.97) within 3 months. Low risk pre-stroke CHA sub /sub DS sub /sub -VASc score has high specificity for good functional outcome (AF: 0.99, 0.98-0.994 no AF: 0.94, 0.93-0.95) at 3 months. b i Conclusions: /i /b The pre-stroke CHA sub /sub DS sub /sub -VASc score appears to be a simple tool for identifying patients at lower risk of poor outcomes and serious cardiac complications within 3 months following ischaemic stroke in patients with and without AF.
Publisher: Whitehouse Publishing
Date: 11-2020
DOI: 10.47795/UPYU3565
Abstract: The field of stroke has rapidly advanced in recent years with more effective reperfusion therapies (thrombolysis and endovascular thrombectomy) applied to a broader range of patients, including using imaging-based selection to treat beyond standard time windows. Recent trials have provided signals that neuroprotection and specific treatments for intracerebral haemorrhage may be achievable. The range of targeted secondary prevention strategies has also expanded, particularly with direct oral anticoagulants, more potent lipid lowering agents and patent foramen ovale closure.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-06-2023
DOI: 10.1212/WNL.0000000000207536
Abstract: There is growing evidence for endovascular thrombectomy (EVT) in patients with large ischemic core infarct and large vessel occlusion (LVO). The objective of this study was to compare the efficacy and safety of EVT vs medical management (MM) using a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs). We searched the PubMed, Embase, Cochrane Library, and Web of Science databases to obtain articles related to mechanical thrombectomy for large ischemic core from inception until February 10, 2023. The primary outcome was independent ambulation (modified Rankin Scale [mRS] 0–3). Effect sizes were computed as risk ratio (RR) with random-effect or fixed-effect models. The quality of articles was evaluated through the Cochrane risk assessment tool and the Newcastle-Ottawa Scale. This study was registered in PROSPERO (CRD42023396232). A total of 5,395 articles were obtained through the search and articles that did not meet the inclusion criteria were excluded by review of the title, abstract, and full text. Finally, 3 RCTs and 10 cohort studies met the inclusion criteria. The RCT analysis showed that EVT improved the 90-day functional outcomes of patients with large ischemic core with high-quality evidence, including independent ambulation (mRS 0–3: RR 1.78, 95% CI 1.28–2.48, p 0.001) and functional independence (mRS 0–2: RR 2.59, 95% CI 1.89–3.57, p 0.001), but without significantly increasing the risk of symptomatic intracranial hemorrhage (sICH: RR 1.83, 95% CI 0.95–3.55, p = 0.07) or early mortality (RR 0.95, 95% CI 0.78–1.16, p = 0.61). Analysis of the cohort studies showed that EVT improved functional outcomes of patients without an increase in the incidence in sICH. This systematic review and meta-analysis indicates that in patients with LVO stroke with a large ischemic core, EVT was associated with improved functional outcomes over MM without increasing sICH risk. The results of ongoing RCTs may provide further insight in this patient population.
Publisher: Oxford University Press (OUP)
Date: 07-12-2011
DOI: 10.1093/JNCI/DJR381
Abstract: Fine needle aspiration cytology (FNAC) is usually used to evaluate palpable nodes in patients with melanoma. The goal of our study is to review the sensitivity and specificity of this technique when applied to palpable but also to nonpalpable nodes. FNAC was performed during 1984-2007 in 1279 patients with suspicious lesions and/or lymph nodes. Indications for biopsy included increased size and/or palpability of nodes or abnormal ultrasound findings such as increased perfusion or focal lesions within the lymph nodes. The sensitivity, specificity, and positive and negative predictive values of FNACs guided by palpation or ultrasound were calculated for all patients and for subgroups of patients with palpable nodes or nonpalpable but sonomorphologically suspicious nodes. A total of 2446 FNACs were performed in 1279 melanoma patients, of which 2011 (82.2%) FNACs had clinically or histologically confirmed results. Increased size and/or palpability of nodes was observed in 376 (29.4%) of 1279 patients, and abnormal ultrasound findings occurred for 903 (70.6%), indicating that a biopsy was needed. FNACs guided by palpation had sensitivity, specificity, and positive and negative predictive values similar to that of FNACs guided by ultrasound (sensitivity = 98.4% vs 97.2%, specificity = 100% vs 99.8%, positive predictive value = 100% vs 99.9%, and negative predictive value = 95.2% vs 96.4%, for palpation-guided FNACs vs ultrasound-guided FNACs, respectively). Results did not differ between patients with the palpable nodes and patients with nonpalpable but sonomorphologically suspicious nodes. Ultrasound-guided FNAC of suspicious lymph nodes and lesions in melanoma patients has a high sensitivity and specificity, and FNAC should not be limited to palpable nodes. FNAC of normal-sized nodes and/or lymph nodes with abnormal ultrasound findings can be used to identify early metastatic disease.
Publisher: BMJ
Date: 30-11-2021
Abstract: Haematoma growth is common early after intracerebral haemorrhage (ICH), and is a key determinant of outcome. Tranexamic acid, a widely available antifibrinolytic agent with an excellent safety profile, may reduce haematoma growth. Stopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units (STOP-MSU) is a phase II double-blind, randomised, placebo-controlled, multicentre, international investigator-led clinical trial, conducted within the estimand statistical framework. In patients with spontaneous ICH, treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with placebo. A s le size of 180 patients (90 in each arm) would be required to detect an absolute difference in the primary outcome of 20% (placebo 39% vs treatment 19%) under a two-tailed significance level of 0.05. An adaptive s le size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 patients. Participants will receive 1 g intravenous tranexamic acid over 10 min, followed by 1 g intravenous tranexamic acid over 8 hours or matching placebo. The primary efficacy measure is the proportion of patients with haematoma growth by 24±6 hours, defined as either ≥33% relative increase or ≥6 mL absolute increase in haematoma volume between baseline and follow-up CT scan. We describe the rationale and protocol of STOP-MSU, a phase II trial of tranexamic acid in patients with ICH within 2 hours from onset, based in participating mobile stroke units and emergency departments.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-05-2023
DOI: 10.1212/WNL.0000000000207138
Abstract: The safety and efficacy of tenecteplase (TNK) in patients with tandem lesion (TL) stroke is unknown. We performed a comparative analysis of TNK and alteplase in patients with TLs. We first compared the treatment effect of TNK and alteplase in patients with TLs using in idual patient data from the EXTEND-IA TNK trials. We evaluated intracranial reperfusion at initial angiographic assessment and 90-day modified Rankin scale (mRS) with ordinal logistic and Firth regression models. Because 2 key outcomes, mortality and symptomatic intracranial hemorrhage (sICH), were few in number among those who received alteplase in the EXTEND-IA TNK trials, we generated pooled estimates for these outcomes by supplementing trial data with estimates of incidence obtained through a meta-analysis of studies identified in a systematic review. We then calculated unadjusted risk differences to compare the pooled estimates for those receiving alteplase with the incidence observed in the trial among those receiving TNK. Seventy-one of 483 patients (15%) in the EXTEND-IA TNK trials possessed a TL. In patients with TLs, intracranial reperfusion was observed in 11/56 (20%) of TNK-treated patients vs 1/15 (7%) alteplase-treated patients (adjusted odds ratio 2.19 95% CI 0.28–17.29). No significant difference in 90-day mRS was observed (adjusted common odds ratio 1.48 95% CI 0.44–5.00). A pooled study-level proportion of alteplase-associated mortality and sICH was 0.14 (95% CI 0.08–0.21) and 0.09 (95% CI 0.04–0.16), respectively. Compared with a mortality rate of 0.09 (95% CI 0.03–0.20) and an sICH rate of 0.07 (95% CI 0.02–0.17) in TNK-treated patients, no significant difference was observed. Functional outcomes, mortality, and sICH did not significantly differ between patients with TLs treated with TNK and those treated with alteplase. This study provides Class III evidence that TNK is associated with similar rates of intracranial reperfusion, functional outcome, mortality, and sICH compared with alteplase in patients with acute stroke due to TLs. However, the CIs do not rule out clinically important differences. t2/show/NCT02388061 t2/show/NCT03340493.
Publisher: Wiley
Date: 17-01-2023
DOI: 10.1002/ANA.26587
Abstract: Reperfusion therapy is highly beneficial for ischemic stroke. Reduction in both infarct growth and edema are plausible mediators of clinical benefit with reperfusion. We aimed to quantify these mediators and their interrelationship. In a pooled, patient‐level analysis of the EXTEND‐IA trials and SELECT study, we used a mediation analysis framework to quantify infarct growth and cerebral edema (midline shift) mediation effect on successful reperfusion (modified Treatment in Cerebral Ischemia ≥ 2b) association with functional outcome (modified Rankin Scale distribution). Furthermore, we evaluated an additional pathway to the original hypothesis, where infarct growth mediated successful reperfusion effect on midline shift. A total 542 of 665 (81.5%) eligible patients achieved successful reperfusion. Baseline clinical and imaging characteristics were largely similar between those achieving successful versus unsuccessful reperfusion. Median infarct growth was 12.3ml (interquartile range [IQR] = 1.8–48.4), and median midline shift was 0mm (IQR = 0–2.2). Of 249 (37%) demonstrating a midline shift of ≥1mm, median shift was 2.75mm (IQR = 1.89–4.21). Successful reperfusion was associated with reductions in both predefined mediators, infarct growth (β = −1.19, 95% confidence interval [CI] = −1.51 to −0.88, p 0.001) and midline shift (adjusted odds ratio = 0.36, 95% CI = 0.23–0.57, p 0.001). Successful reperfusion association with improved functional outcome (adjusted common odds ratio [acOR] = 2.68, 95% CI = 1.86–3.88, p 0.001) became insignificant (acOR = 1.39, 95% CI = 0.95–2.04, p = 0.094) when infarct growth and midline shift were added to the regression model. Infarct growth and midline shift explained 45% and 34% of successful reperfusion effect, respectively. Analysis considering an alternative hypothesis demonstrated consistent results. In this mediation analysis from a pooled, patient‐level cohort, a significant proportion (~80%) of successful reperfusion effect on functional outcome was mediated through reduction in infarct growth and cerebral edema. Further studies are required to confirm our findings, detect additional mediators to explain successful reperfusion residual effect, and identify novel therapeutic targets to further enhance reperfusion benefits. ANN NEUROL 2023 :793–804
Publisher: SAGE Publications
Date: 08-05-2013
Abstract: Changes in collateral blood flow, which sustains brain viability distal to arterial occlusion, may impact infarct evolution but have not previously been demonstrated in humans. We correlated leptomeningeal collateral flow, assessed using novel perfusion magnetic resonance imaging (MRI) processing at baseline and 3 to 5 days, with simultaneous assessment of perfusion parameters. Perfusion raw data were averaged across three consecutive slices to increase leptomeningeal collateral vessel continuity after subtraction of baseline signal analogous to digital subtraction angiography. Changes in collateral quality, Tmax hypoperfusion severity, and infarct growth were assessed between baseline and days 3 to 5 perfusion-diffusion MRI. Acute MRI was analysed for 88 patients imaged 3 to 6 hours after ischemic stroke onset. Better collateral flow at baseline was associated with larger perfusion-diffusion mismatch (Spearman's Rho 0.51, P 0.001) and smaller baseline diffusion lesion volume (Rho − 0.70, P 0.001). In 30 patients without reperfusion at day 3 to 5, deterioration in collateral quality between baseline and subacute imaging was strongly associated with absolute ( P = 0.02) and relative ( P 0.001) infarct growth. The deterioration in collateral grade correlated with increased mean Tmax hypoperfusion severity (Rho − 0.68, P 0.001). Deterioration in Tmax hypoperfusion severity was also significantly associated with absolute ( P = 0.003) and relative ( P = 0.002) infarct growth. Collateral flow is dynamic and failure is associated with infarct growth.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2011
DOI: 10.1161/STROKEAHA.110.609016
Abstract: The ischemic penumbra may be classical, with complete annular configuration around the infarct core, or nonclassical with a more fragmented pattern. We tested the hypotheses that these penumbral patterns may: be associated with specific predictive factors, influence infarct growth and clinical outcome, and influence the effect of tissue plasminogen activator (t-PA). Using the EPITHET/DEFUSE data set, in which patients received alteplase or placebo 3 to 6 hours poststroke, perfusion-weighted imaging and diffusion-weighted imaging images were analyzed. These mismatch patterns were defined as “classical” or “nonclassical.” Multivariate analysis was used to identify variables associated with mismatch patterns, the effect of t-PA, as well as the relationship between mismatch patterns, infarct growth, and clinical outcomes. We included 158 patients (median age, 74 years median National Institute of Health Stroke Scale score, 12). Multivariate analysis indicated that the factors associated with classical mismatch pattern type were large mismatch volume ( P .001) and cortical infarct location ( P =0.036). Infarct growth, clinical outcome, and the efficacy of t-PA were not statistically different between patterns. Coregistered mismatch volume and cortical location of infarction were the important factors associated with presence of the classical mismatch pattern. The lack of effect of the type of mismatch patterns on infarct growth, clinical outcomes, or the benefit of t-PA would suggest that mismatch topography is less important during the hyperacute phase of ischemic stroke than during subacute phase.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2022
DOI: 10.1161/STROKEAHA.121.036670
Abstract: Emerging data suggest tissue within the infarct lesion is not homogenously damaged following ischemic stroke but has a gradient of injury. Using blood-brain-barrier (BBB) disruption as a marker of tissue injury, we tested whether therapeutic reperfusion improves clinical outcome by reducing the severity of tissue injury within the infarct in patients with ischemic stroke. In a pooled analysis of patients treated for anterior circulation large vessel occlusion in the EXTEND-IA TNK (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke) and EXTEND-IA part-2 (Determining the Optimal Dose of Tenecteplase Before Endovascular Therapy for Ischaemic Stroke) trials, post-treatment BBB permeability at 24 hours was calculated based on the extent of T1-brightening by extravascular gadolinium on T2* perfusion-weighted imaging and measured within the diffusion-weighted-imaging lesion. First, to determine the clinical significance of BBB disruption as a marker of severity of tissue injury, we examined the association between post-treatment BBB permeability and functional outcome. Second, we performed an exploratory (reperfusion, BBB permeability, functional outcome) mediation analysis to estimate the proportion of the reperfusion-outcome relationship that is mediated by change in BBB permeability. In the 238 patients analyzed, an increased BBB permeability measured within the infarct at 24 hours was associated with a reduced likelihood of favorable outcome (90-day modified Rankin Scale score of ≤2) after adjusting for age, baseline National Institutes of Health Stroke Scale, premorbid modified Rankin Scale, infarct topography, laterality, thrombolytic agent, sex, parenchymal hematoma, and follow-up infarct volume (adjusted odds ratio, 0.86 [95% CI, 0.75–0.98] P =0.023). Mediation analysis suggested reducing the severity of tissue injury (as estimated by BBB permeability) accounts for 18.2% of the association between reperfusion and favorable outcome, as indicated by a reduction in the regression coefficient of reperfusion after addition of BBB permeability as a covariate. In patients with ischemic stroke, reduced severity of tissue injury within the infarct, as determined by assessing the integrity of the BBB, is independently associated with improved functional outcome. In addition to reducing diffusion-weighted imaging-defined infarct volume, reperfusion may also improve clinical outcome by reducing tissue injury severity within the infarct.
Publisher: Elsevier BV
Date: 04-2023
Publisher: AMPCo
Date: 07-04-2020
DOI: 10.5694/MJA2.50570
Publisher: SAGE Publications
Date: 02-02-2023
DOI: 10.1177/17474930231154390
Abstract: Alteplase is the only approved thrombolytic agent for acute stroke. An alternative plasminogen activator, tenecteplase, has been previously shown to increase early biological effectiveness (reperfusion) resulting in early clinical recovery in acute stroke patients with target mismatch on perfusion imaging however, phase III data are lacking. In this study, we assess the efficacy and safety of tenecteplase compared to alteplase in acute stroke patients with target mismatch on perfusion imaging. Tenecteplase (0.25 mg/kg) versus alteplase (0.9 mg/kg) for Stroke Thrombolysis Evaluation (TASTE) is a multicentre, prospective, randomized, open-label, blinded-endpoint (PROBE), controlled phase III non-inferiority trial (2 arms with 1:1 randomization) with an adaptive s le size re-estimation in patients with acute ischemic stroke meeting target mismatch criteria on perfusion imaging. Recruiting 728 patients (1:1 tenecteplase vs alteplase) would yield 90% power (two-sided alpha 0.05) to detect a treatment effect of 8% (26% modified Rankin scale (mRS) 0–1 in alteplase arm and 34% mRS 0–1 in tenecteplase arm), with an absolute non-inferiority margin of 3%. Following the pre-planned “promising zone” adaptive s le size re-estimation, the final s le size was set at 832 patients. The primary outcome measure is the proportion of patients with an mRS score of 0–1 at 3 months. Secondary outcomes include the categorical shift in mRS at 3 months the proportion of patients with: mRS 0–2, 5–6, and 6 reduction of the National Institutes of Health Stroke Scale (NIHSS) by 8 or more points or reaching 0–1 at 24 h symptomatic intracerebral hemorrhage within 36 h and death. This pivotal trial will provide important data on the role of tenecteplase in acute ischemic stroke, and the use of imaging-based treatment decision-making for stroke thrombolysis. Trial Registration: ACTRN12613000243718, EudraCT 2015-002657-36
Publisher: Wiley
Date: 18-03-2022
DOI: 10.1111/ENE.15322
Publisher: Massachusetts Medical Society
Date: 12-03-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-01-2023
DOI: 10.1161/CIRCULATIONAHA.122.063366
Abstract: Despite the well-established potent benefit of mechanical thrombectomy (MT) for large vessel occlusion (LVO) stroke, access to MT has not been studied globally. We conducted a worldwide survey of countries on 6 continents to define MT access (MTA), the disparities in MTA, and its determinants on a global scale. Our survey was conducted in 75 countries through the Mission Thrombectomy 2020+ global network between November 22, 2020, and February 28, 2021. The primary end points were the current annual MTA, MT operator availability, and MT center availability. MTA was defined as the estimated proportion of patients with LVO receiving MT in a given region annually. The availability metrics were defined as ([current MT operators×50/current annual number of estimated thrombectomy-eligible LVOs]×100 = MT operator availability) and ([current MT centers×150/current annual number of estimated thrombectomy-eligible LVOs]×100= MT center availability). The metrics used optimal MT volume per operator as 50 and an optimal MT volume per center as 150. Multivariable-adjusted generalized linear models were used to evaluate factors associated with MTA. We received 887 responses from 67 countries. The median global MTA was 2.79% (interquartile range, 0.70–11.74). MTA was .0% for 18 (27%) countries and 0 for 7 (10%) countries. There was a 460-fold disparity between the highest and lowest nonzero MTA regions and low-income countries had 88% lower MTA compared with high-income countries. The global MT operator availability was 16.5% of optimal and the MT center availability was 20.8% of optimal. On multivariable regression, country income level (low or lower–middle versus high: odds ratio, 0.08 [95% CI, 0.04–0.12]), MT operator availability (odds ratio, 3.35 [95% CI, 2.07–5.42]), MT center availability (odds ratio, 2.86 [95% CI, 1.84–4.48]), and presence of prehospital acute stroke bypass protocol (odds ratio, 4.00 [95% CI, 1.70–9.42]) were significantly associated with increased odds of MTA. Access to MT on a global level is extremely low, with enormous disparities between countries by income level. The significant determinants of MT access are the country’s per capita gross national income, prehospital LVO triage policy, and MT operator and center availability.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2020
Publisher: Springer Science and Business Media LLC
Date: 18-04-2012
DOI: 10.1007/S12975-012-0167-8
Abstract: The mismatch between a larger perfusion lesion and smaller diffusion lesion on magnetic resonance imaging is a validated signal of the ischemic penumbra, namely the region at risk in acute ischemic stroke that is critically hypoperfused and the target of reperfusion therapies. Clinical trials have shown strong correlations between reperfusion in mismatch patients and improved clinical outcomes. Attenuation of infarct growth is associated with reperfusion and corresponding clinical gains. Using computed tomography perfusion, the mismatch between relative cerebral blood flow or cerebral blood volume and perfusion delay is a comparable penumbral marker. Automated techniques allow rapid quantitative assessment of mismatch with thresholding to exclude benign oligemia. The penumbra is often present beyond the current 4.5-h time window, defined for the use of intravenous tPA. Treatment beyond this time point remains investigational. Although the efficacy of thrombolysis in mismatch patients requires further validation in randomized trials, there is now sufficient evidence to recommend that advanced neuroimaging of mismatch should be used for selection of delayed therapies in phase 3 trials.
Publisher: BMJ
Date: 25-01-2013
Abstract: CT perfusion (CTP) is rapid and accessible for emergency ischaemic stroke diagnosis. The feasibility of introducing CTP and diagnostic accuracy versus non-contrast CT (NCCT) in a tertiary hospital were assessed. All patients presenting <9 h from stroke onset or with wake-up stroke were eligible for CTP (Siemens 16-slice scanner, 2×24 mm slabs) unless they had estimated glomerular filtration rate (eGFR)<50 ml/min or diabetes with unknown eGFR. NCCT was assessed by a radiologist and stroke neurologist for early ischaemic change and hyperdense arteries. CTP was assessed for prolonged time to peak and reduced cerebral blood flow. Technical adequacy was defined as 2 CTP slabs of sufficient quality to diagnose stroke. Between January 2009 and September 2011, 1152 ischaemic stroke patients were admitted, 475 (41%) were <9 h/wake-up onset. Of these, 276 (58%) had CTP. Reasons for not performing CTP were diabetes with unknown eGFR (48 (10%)), known kidney disease (36 (8%)), established infarct on NCCT (27 (6%)), posterior circulation syndrome (25 (5%)) and patient motion/instability (16 (3%)). Clinician discretion excluded a further 47 (10%). CTP was more frequently diagnostic than NCCT (80% vs 50%, p<0.001). Non-diagnostic CTP was due to lacunar infarction (28 (10%)), infarct outside slab coverage (21 (8%)), technical failure (4 (1%)) and reperfusion (2 (0.7%)). Normal CTP in 86/87 patients with stroke mimics supported withholding tissue plasminogen activator. CTP technical adequacy improved from 56% to 86% (p<0.001) after the first 6 months. Median time for NCCT/CTP/arch-vertex CT angiogram (including processing and interpretation) was 12 min. No clinically significant contrast nephropathy occurred. CTP in suspected stroke is widely applicable, rapid and increases diagnostic confidence.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2010
DOI: 10.1161/STROKEAHA.109.563767
Abstract: Background and Purpose— Reliable predictors of hemorrhagic transformation (HT) after stroke thrombolysis have not been identified. We analyzed hemorrhage in a randomized trial of tissue plasminogen activator (t-PA) vs placebo in ischemic stroke patients. We hypothesized that acute diffusion-weighted imaging (DWI) lesion volumes would be larger and blood pressures would be higher in patients with HT. Methods— HT was assessed 2 to 5 days after treatment in 97 patients. Hemorrhage was assessed by using susceptibility-weighted imaging sequences and was classified as petechial hemorrhagic infarction (HI) or parenchymal hematoma (PH). Results— PH was more frequent in t-PA– (11/49) than in placebo- (4/48) treated patients ( P =0.049). Patients with PH had larger DWI lesion volumes (63.1±56.1 mL) than did those without HT (27.6±39.0 mL, P =0.033). There were no differences in baseline systolic blood pressure (SBP) between patients with and without hemorrhage. Weighted average SBP 24 hours after treatment was higher in patients with PH (159.4±18.8 mL, P .011) relative to those without HT (143.1±20.0 mL). Multinomial logistic regression indicated that PH was predicted by DWI lesion volume (odds ratio=1.16 per 10 mL 95% CI, 1.03 to 1.30), atrial fibrillation (odds ratio=9.33 95% CI, 2.30 to 37.94), and 24-hour weighted average SBP (odds ratio=1.59 per 10 mm Hg 95% CI, 1.14 to 2.23). Conclusions— Pretreatment DWI lesion volume and postthrombolysis BP are both predictive of HT. Consideration should be given to excluding patients with very large baseline DWI volumes from t-PA therapy and to more stringent BP control after stroke thrombolysis.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2021
DOI: 10.1161/STROKEAHA.120.030859
Abstract: In ischemic stroke, intravenous tenecteplase is noninferior to alteplase in selected patients and has some practical advantages. Several stroke centers in New Zealand changed to routine off-label intravenous tenecteplase due to improved early recanalization in large vessel occlusion, inconsistent access to thrombectomy within stroke networks, and for consistency in treatment protocols between patients with and without large vessel occlusion. We report the feasibility and safety outcomes in tenecteplase-treated patients. We performed a retrospective analysis of consecutive patients thrombolyzed with intravenous tenecteplase at 1 comprehensive and 2 regional stroke centers from July 14, 2018, to February 29, 2020. We report the baseline clinical characteristics, rates of symptomatic intracranial hemorrhage, and angioedema. These were then compared with patient outcomes with those treated with intravenous alteplase at 2 other comprehensive stroke centers. Multivariable mixed-effects logistic regression models were performed assessing the association of tenecteplase with symptomatic intracranial hemorrhage and independent outcome (modified Rankin Scale score, 0–2) at day 90. There were 165 patients treated with tenecteplase and 254 with alteplase. Age (75 versus 74 years), sex (56% versus 60% male), National Institutes of Health Stroke Scale scores (8 versus 10), median door-to-needle times (47 versus 48 minutes), or onset-to-needle time (129 versus 130 minutes) were similar between the groups. Symptomatic intracranial hemorrhage occurred in 3 (1.8% [95% CI, 0.4–5.3]) tenecteplase patients compared with 7 (2.7% [95% CI, 1.1–5.7]) alteplase patients ( P =0.75). There were no differences between tenecteplase and alteplase in the rates of angioedema (4 [2.4% 95% CI, 0.7–6.2] versus 1 [0.4% 95% CI, 0.01–2.2], P =0.08) or 90-day functional independence (100 [61%] versus 140 [57%], P =0.47), respectively. In mixed-effects logistic regression models, there was no significant association between thrombolytic choice and symptomatic intracranial hemorrhage (odds ratio tenecteplase, 0.62 [95% CI, 0.14–2.80], P =0.53) or functional independence (odds ratio tenecteplase, 1.20 [95% CI, 0.74–1.95], P =0.46). Routine use of tenecteplase for stroke thrombolysis was feasible and had comparable safety profile and outcome to alteplase.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2023
DOI: 10.1161/STROKEAHA.122.041061
Abstract: Intracranial occlusion site, contrast permeability, and clot burden are thrombus characteristics that influence alteplase-associated reperfusion. In this study, we assessed the reperfusion efficacy of tenecteplase and alteplase in subgroups based on these characteristics in a pooled analysis of the EXTEND-IA TNK trial (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke). Patients with large vessel occlusion were randomized to treatment with tenecteplase (0.25 or 0.4 mg/kg) or alteplase before thrombectomy in hospitals across Australia and New Zealand (2015–2019). The primary outcome, early reperfusion, was defined as the absence of retrievable thrombus or % reperfusion on first-pass angiogram. We compared the effect of tenecteplase versus alteplase overall, and in subgroups, based on the following measured with computed tomography angiography: intracranial occlusion site, contrast permeability (measured via residual flow grades), and clot burden (measured via clot burden scores). We adjusted for covariates using mixed effects logistic regression models. Tenecteplase was associated with higher odds of early reperfusion (75/369 [20%] versus alteplase: 9/96 [9%], adjusted odds ratio [aOR], 2.18 [95% CI, 1.03–4.63]). The difference between thrombolytics was notable in occlusions with low clot burden (tenecteplase: 66/261 [25%] versus alteplase: 5/67 [7%], aOR, 3.93 [95% CI, 1.50–10.33]) when compared to high clot burden lesions (tenecteplase: 9/108 [8%] versus alteplase: 4/29 [14%], aOR, 0.58 [95% CI, 0.16–2.06] P interaction =0.01). We did not observe an association between contrast permeability and tenecteplase treatment effect (permeability present: aOR, 2.83 [95% CI, 1.00–8.05] versus absent: aOR, 1.98 [95% CI, 0.65–6.03] P interaction =0.62). Tenecteplase treatment effect was superior with distal M1 or M2 occlusions (53/176 [30%] versus alteplase: 4/42 [10%], aOR, 3.73 [95% CI, 1.25–11.11]), but both thrombolytics had limited efficacy with internal carotid artery occlusions (tenecteplase 1/73 [1%] versus alteplase 1/19 [5%], aOR, 0.22 [95% CI, 0.01–3.83] P interaction =0.16). Tenecteplase demonstrates superior early reperfusion versus alteplase in lesions with low clot burden. Reperfusion efficacy remains limited in internal carotid artery occlusions and lesions with high clot burden. Further innovation in thrombolytic therapies are required.
Publisher: S. Karger AG
Date: 2011
DOI: 10.1159/000332028
Abstract: i Background: /i Atrial fibrillation (AF) is associated with worse outcomes following ischemic stroke and more frequent cardiac complications in the general population. We aimed to establish whether early cardiac complications contribute to the poorer ischemic stroke outcomes in patients with AF, independent of baseline differences in age, stroke severity and cardiovascular risk factors. This might have important implications for acute stroke management in patients with AF. i Methods: /i We searched VISTA-Acute, an academic database containing standardized data for 28,131 patients from 30 randomized-controlled acute stroke trials and 1 stroke registry, for imaging-confirmed placebo-treated patients with complete documentation of baseline demographics, cardiovascular risk factors, presence or absence of AF, neurologic impairment [National Institutes of Health Stroke Scale (NIHSS)], cardiac complications and 3-month outcome (modified Rankin Scale). A total of 2,865 patients from 6 randomized-controlled trials met the selection criteria, of whom 819 had AF. Binary logistic regression modeling was used to determine the independent effect of AF on stroke outcome and serious cardiac adverse events (SCAE), a composite end point including acute coronary syndrome, symptomatic heart failure, cardiopulmonary arrest, ventricular tachycardia, ventricular fibrillation and cardiac mortality. i Results: /i All patients were enrolled into the source trials within 24 h of stroke onset. At baseline, patients with AF were older (mean 75 vs. 67 years, p 0.001) and had greater neurologic impairment (median NIHSS 15 vs. 13, p 0.001). The median time to first cardiac adverse event was 3 days [median difference 0, 95% confidence interval (CI) 0–1, p = 0.06] for both patients with and without AF. SCAE occurred more frequently [14.2 vs. 6%, odds ratio (OR) = 2.58, 95% CI 1.97–3.37] in patients with AF, particularly cardiac mortality (4.9 vs. 2.6%, OR = 1.89, 95% CI 1.25–2.88), symptomatic heart failure (6.5 vs. 2.2%, OR = 3.01, 95% CI 2.01–4.50), and ventricular tachycardia and/or fibrillation (2.4 vs. 0.8%, OR = 3.18, 95% CI 1.64–6.16). At 3 months, AF was independently associated with SCAE (OR = 2.14, 95% CI 1.61–2.86) and early mortality (OR = 1.44, 95% CI 1.14–1.81) after adjusting for all baseline imbalances. i Conclusion: /i Early SCAE are common after stroke and are independently associated with the presence of AF. Given that many cardiac complications are potentially remediable, these results highlight the need for more rigorous surveillance for cardiac complications in acute ischemic stroke patients with AF.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2022
DOI: 10.1161/STROKEAHA.120.034019
Abstract: The National Institutes of Health Stroke Scale (NIHSS) underestimates clinical severity in posterior circulation stroke and patients presenting with low NIHSS may be considered ineligible for reperfusion therapies. This study aimed to develop a modified version of the NIHSS, the Posterior NIHSS (POST-NIHSS), to improve NIHSS prognostic accuracy for posterior circulation stroke patients with mild-moderate symptoms. Clinical data of consecutive posterior circulation stroke patients with mild-moderate symptoms (NIHSS ), who were conservatively managed, were retrospectively analyzed from the Basilar Artery Treatment and Management registry. Clinical features were assessed within 24 hours of symptom onset dysphagia was assessed by a speech therapist within 48 hours of symptom onset. Random forest classification algorithm and constrained optimization were used to develop the POST-NIHSS in the derivation cohort. The POST-NIHSS was then validated in a prospective cohort. Poor outcome was defined as modified Rankin Scale score ≥3 at 3 months. We included 202 patients (mean [SD] age 63 [14] years, median NIHSS 3 [interquartile range, 1–5]) in the derivation cohort and 65 patients (mean [SD] age 63 [16] years, median NIHSS 2 [interquartile range, 1–4]) in the validation cohort. In the derivation cohort, age, NIHSS, abnormal cough, dysphagia and gait/truncal ataxia were ranked as the most important predictors of functional outcome. POST-NIHSS was calculated by adding 5 points for abnormal cough, 4 points for dysphagia, and 3 points for gait/truncal ataxia to the baseline NIHSS. In receiver operating characteristic analysis adjusted for age, POST-NIHSS area under receiver operating characteristic curve was 0.80 (95% CI, 0.73–0.87) versus NIHSS area under receiver operating characteristic curve, 0.73 (95% CI, 0.64–0.83), P =0.03. In the validation cohort, POST-NIHSS area under receiver operating characteristic curve was 0.82 (95% CI, 0.69–0.94) versus NIHSS area under receiver operating characteristic curve 0.73 (95% CI, 0.58–0.87), P =0.04. POST-NIHSS showed higher prognostic accuracy than NIHSS and may be useful to identify posterior circulation stroke patients with NIHSS at higher risk of poor outcome.
Publisher: Elsevier BV
Date: 06-2000
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2011
DOI: 10.1161/STROKEAHA.111.618355
Abstract: CT perfusion (CTP) is widely and rapidly accessible for imaging acute ischemic stroke but has limited validation. Cerebral blood volume (CBV) has been proposed as the best predictor of infarct core. We tested CBV against other common CTP parameters using contemporaneous diffusion MRI. Patients with acute ischemic stroke hours after onset had CTP and diffusion MRI hour apart, before any reperfusion therapies. CTP maps of time to peak (TTP), absolute and relative CBV, cerebral blood flow (CBF), mean transit time (MTT), and time to peak of the deconvolved tissue residue function (Tmax) were generated. The diffusion lesion was manually outlined to its maximal visual extent. Receiver operating characteristic (ROC) analysis area under the curve (AUC) was used to quantify the correspondence of each perfusion parameter to the coregistered diffusion-weighted imaging lesion. Optimal thresholds were determined (Youden index). In analysis of 98 CTP slabs (54 patients, median onset to CT 190 minutes, median CT to MR 30 minutes), relative CBF performed best (AUC, 0.79 95% CI, 0.77–81), significantly better than absolute CBV (AUC, 0.74 95% CI, 0.73–0.76). The optimal threshold was % of mean contralateral CBF. Specificity was reduced by low CBF/CBV in noninfarcted white matter in cases with reduced contrast bolus intensity and leukoaraiosis. In contrast to previous reports, CBF corresponded with the acute diffusion-weighted imaging lesion better than CBV, although no single threshold avoids detection of false-positive regions in unaffected white matter. This relates to low signal-to-noise ratio in CTP maps and emphasizes the need for optimized acquisition and postprocessing.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2023
DOI: 10.1161/STROKEAHA.122.042200
Abstract: Infarct in a new territory (INT) is a known complication of endovascular stroke therapy. We assessed the incidence of INT, outcomes after INT, and the impact of concurrent treatments with intravenous thrombolysis and nerinetide. Data are from ESCAPE-NA1 trial (Safety and Efficacy of Nerinetide [NA-1] in Subjects Undergoing Endovascular Thrombectomy for Stroke), a multicenter, international randomized study that assessed the efficacy of intravenous nerinetide in subjects with acute ischemic stroke who underwent endovascular thrombectomy within 12 hours from onset. Concurrent treatment and outcomes were collected as part of the trial protocol. INTs were identified on core lab imaging review of follow-up brain imaging and defined by the presence of infarct in a new vascular territory, outside the baseline target occlusion(s) on follow-up brain imaging (computed tomography or magnetic resonance imaging). INTs were classified by maximum diameter ( , 2–20, and mm), number, and location. The association between INT and clinical outcomes (modified Rankin Scale and death) was assessed using standard descriptive techniques and adjusted estimates of effect were derived from Poisson regression models. Among 1092 patients, 103 had INT (9.3%, median age 69.5 years, 49.5% females). There were no differences in baseline characteristics between those with versus without INT. Most INTs (91/103, 88.3%) were not associated with visible occlusions on angiography and 39 out of 103 (37.8%) were mm in maximal diameter. The most common INT territory was the anterior cerebral artery (27.8%). Almost half of the INTs were multiple (46 subjects, 43.5%, range, 2–12). INT was associated with poorer outcomes as compared to no INT on the primary outcome of modified Rankin Scale score of 0 to 2 at 90 days (adjusted risk ratio, 0.71 [95% CI, 0.57–0.89]). Infarct volume in those with INT was greater by a median of 21 cc compared with those without, and there was a greater risk of death as compared to patients with no INT (adjusted risk ratio, 2.15 [95% CI, 1.48–3.13]). Infarcts in a new territory are common in in iduals undergoing endovascular thrombectomy for acute ischemic stroke and are associated with poorer outcomes. Optimal therapeutic approaches, including technical strategies, to reduce INT represent a new target for incremental quality improvement of endovascular thrombectomy. URL: www.clinicaltrials.gov Unique identifier: NCT02930018.
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: SAGE Publications
Date: 20-06-2013
DOI: 10.1111/IJS.12101
Abstract: In this issue of the journal, Sakamoto et al. present an analysis of diffusion lesion evolution in acute ischemic stroke patients first imaged less than three-hours from stroke onset. Although temporary lesion volume reduction was observed following reperfusion, the affected regions were generally abnormal on follow-up fluid attenuated inversion recovery imaging, indicating lack of tissue salvage. Taken in conjunction with other recent articles, it seems that temporary postreperfusion ‘reversal’ of diffusion lesions is quite common but usually does not translate to permanent tissue salvage. A minority of patients demonstrate permanent reversibility of a component of the acute diffusion lesion. This is dependent on early reperfusion and is more frequent when patients are treated within three-hours. Early reperfusion is clearly associated with a reduction in infarct growth through salvage of ischemic penumbra, and this probably contributes more to the favorable neurological outcomes in these patients than the relatively small volumes of diffusion reversal. It is currently unknown whether future therapeutic advances that increase the speed and success rates of reperfusion will increase the proportion of reversibility further and lead to clinically relevant salvage within the diffusion lesion. For the present, it appears that intravenous tissue plasminogen activator rarely achieves substantial permanent reversal of diffusion lesions, even when administered within three-hours.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2022
DOI: 10.1161/STROKEAHA.121.037073
Abstract: Cerebral edema after large hemispheric infarction is associated with poor functional outcome and mortality. Net water uptake (NWU) quantifies the degree of hypoattenuation on unenhanced-computed tomography (CT) and is increasingly used to measure cerebral edema in stroke research. Hemorrhagic transformation and parenchymal contrast staining after thrombectomy may confound NWU measurements. We investigated the correlation of NWU measured postthrombectomy with volumetric markers of cerebral edema and association with functional outcomes. In a pooled in idual patient level analysis of patients presenting with anterior circulation large hemispheric infarction (core 80–300 mL or Alberta Stroke Program Early CT Score ≤5) in the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke trials) data set, cerebral edema was defined as the volumetric expansion of the ischemic hemisphere expressed as a ratio to the contralateral hemisphere(rHV). NWU and midline-shift were compared with rHV as the reference standard on 24-hour follow-up CT, adjusted for hemorrhagic transformation and the use of thrombectomy. Association between edema markers and day 90 functional outcomes (modified Rankin Scale) was assessed using ordinal logistic regression. Overall (n=144), there was no correlation between NWU and rHV (r s =0.055, P =0.51). In sub-group analyses, a weak correlation between NWU with rHV was observed after excluding patients with any degree of hemorrhagic transformation (r s =0.211, P =0.015), which further improved after excluding thrombectomy patients (r s =0.453, P =0.001). Midline-shift correlated strongly with rHV in all sub-group analyses (r s .753, P =0.001). Functional outcome at 90 days was negatively associated with rHV (adjusted common odds ratio, 0.46 [95% CI, 0.32–0.65] P .001) and midline-shift (adjusted common odds ratio, 0.85 [95% CI, 0.78–0.92] P .001) but not NWU (adjusted common odds ratio, 1.00 [95% CI, 0.97–1.03] P =0.84), adjusted for age, baseline National Institutes of Health Stroke Scale, and thrombectomy. Prognostic performance of NWU improved after excluding patients with hemorrhagic transformation and thrombectomy (adjusted odds ratio, 0.90 [95% CI, 0.80–1.02] P =0.10). NWU correlated poorly with conventional markers of cerebral edema and was not associated with clinical outcome in the presence of hemorrhagic transformation and thrombectomy. Measuring NWU postthrombectomy requires validation before implementation into clinical research. At present, the use of NWU should be limited to baseline CT, or follow-up CT only in patients without hemorrhagic transformation or treatment with thrombectomy.
Publisher: SAGE Publications
Date: 11-11-2013
DOI: 10.1111/IJS.12186
Abstract: Magnetic resonance imaging has tremendous potential to illuminate ischemic stroke pathophysiology and guide rational treatment decisions. Clinical applications to date have been largely limited to trials. However, recent analyses of the major clinical studies have led to refinements in selection criteria and improved understanding of the potential implications for the risk vs. benefit of thrombolytic therapy. In parallel, preclinical studies have provided complementary information on the evolution of stroke that is difficult to obtain in humans due to the requirement for continuous or repeated imaging and pathological verification. We review the clinical and preclinical advances that have led to perfusion–diffusion mismatch being applied in phase 3 randomized trials and, potentially, future routine clinical practice.
Publisher: Massachusetts Medical Society
Date: 22-03-2012
Publisher: SAGE Publications
Date: 29-04-2022
DOI: 10.1177/17474930221092262
Abstract: The THRIVE score and the THRIVE-c calculation are validated ischemic stroke outcome prediction tools based on patient variables that are readily available at initial presentation. Randomized controlled trials (RCTs) have demonstrated the benefit of endovascular treatment (EVT) for many patients with large vessel occlusion (LVO), and pooled data from these trials allow for adaptation of the THRIVE-c calculation for use in shared clinical decision making regarding EVT. To extend THRIVE-c for use in the context of EVT, we extracted data from the Virtual International Stroke Trials Archive (VISTA) from 7 RCTs of EVT. Models were built in a randomly selected development cohort using logistic regression that included the predictors from THRIVE-c: age, NIH Stroke Scale (NIHSS) score, presence of hypertension, diabetes mellitus, and/or atrial fibrillation, as well as randomization to EVT and, where available, the Alberta Stroke Program Early CT Score (ASPECTS). Good outcome was achieved in 366/787 (46.5%) of subjects randomized to EVT and in 236/795 (29.7%) of subjects randomized to control (P < 0.001), and the improvement in outcome with EVT was seen across age, NIHSS, and THRIVE-c good outcome prediction. Models to predict outcome using THRIVE elements (age, NIHSS, and comorbidities) together with EVT, with or without ASPECTS, had similar performance by ROC analysis in the development and validation cohorts (THRIVE-EVT ROC area under the curve (AUC) = 0.716 in development, 0.727 in validation, P = 0.30 THRIVE-EVT + ASPECTS ROC AUC = 0.718 in development, 0.735 in validation, P = 0.12). THRIVE-EVT may be used alongside the original THRIVE-c calculation to improve outcome probability estimation for patients with acute ischemic stroke, including patients with or without LVO, and to model the potential improvement in outcomes with EVT for an in idual patient based on variables that are available at initial presentation. Online calculators for THRIVE-c estimation are available at www.thrivescore.org and hrive-score-for-stroke-outcome.
Publisher: S. Karger AG
Date: 2020
DOI: 10.1159/000505847
Abstract: b i Aim: /i /b To evaluate the degree of variability in microstructural injury within and adjacent to regions identified as infarcted tissue using diffusion tensor imaging (DTI). b i Methods: /i /b In this prospective longitudinal study, 18 patients presenting within 12 h of anterior circulation acute ischemic stroke who underwent CT perfusion (CTP) at baseline followed by fluid-attenuated inversion recovery (FLAIR) and DTI 1-month were analyzed. Four regions of interest (ROI) corresponding to the severity of hypoperfusion on CTP within and beyond the radiological infarct lesion defined on FLAIR were segmented. Fractional anisotropy (FA) and mean diffusivity (MD) were quantified for each ROI and compared to a mirror homologue in the contralateral hemisphere. Ipsilateral to contralateral FA and MD ratios were compared across ROIs. b i Results: /i /b Lower FA and higher MD values were observed within both the infarct lesion and the peri-infarct tissue compared with their homologous contralateral brain regions (all comparisons i /i ≤ 0.01). No difference was observed in FA and MD between remote nonhypoperfused tissue and its contralateral homologous region (FA i /i = 0.42, MD i /i ≥ 0.99). The magnitude of asymmetry (ipsilateral/contralateral ratios) of FA and MD was greater with increasing severity of hypoperfusion in a dose-response pattern. Asymmetry greatest in the area of infarction with severe hypoperfusion, followed by infarction with moderate hypoperfusion, the peri-infarct hypoperfused tissue, and lastly the remote nonhypoperfused normal tissue (median on clustered quantile regression i /i ≤ 0.01). b i Conclusion: /i /b A gradient of microstructural injury corresponding to the severity of ischemic insult is present within and beyond conventionally defined infarct boundaries. The traditional dichotomized notion of infarcted versus noninfarcted tissue widely adopted in clinical research and in practice warrants reexamination.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2014
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: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2022
DOI: 10.1161/STROKEAHA.122.039717
Abstract: Leptomeningeal collateral status on baseline computed tomographic angiography (CTA) is associated with clinical outcome after acute ischemic stroke treatment. However, assessment of collateral status is not uniform. To compare 3 different CTA collateral scores (CS) and imaging techniques about their association with clinical outcome. Pooled analysis of patient-level data from the Highly Effective Reperfusion Using Multiple Endovascular Devices collaboration. Patients with large vessel occlusion from 7 randomized controlled trials that compared endovascular thrombectomy with standard medical care were included. Three different CS (Tan CS, regional CS [rCS], and regional Alberta Stroke Program Early CT Score CS) and 2 imaging techniques (single-phase [sCTA] and multiphase/dynamic CTA) were evaluated. Functional independence (modified Rankin Scale score 0–2) at 3 months poststroke was the primary outcome. Furthermore, we assessed the effect of sCTA image acquisition time on collateral status assessment using an adjusted ordinal logistic regression model to obtain predicted values for the trichotomized rCS. Among 1147 pooled patients, 948 (82.7%) had sCTA and 199 (17.3%) multiphase/dynamic CTA as baseline angiography. With all 3 collateral scales, better CSs were associated with better 3-month functional outcome. With sCTA images, the rCS (area under the curve [AUC] 0.63) and regional Alberta Stroke Program Early CT Score CS (AUC 0.62) better predicted functional outcome than the Tan CS (AUC 0.60, respectively P .001 and P =0.02). With multiphase/dynamic CTA images, all collateral scales performed similarly in predicting functional outcome (rCS [AUC 0.61] regional Alberta Stroke Program Early CT Score CS [AUC 0.61] versus Tan CS [AUC 0.61], respectively P =0.93 and P =0.91). Overall, no endovascular thrombectomy treatment effect modification by collateral status (rCS) was demonstrated ( P =0.41). sCTA timing independently influenced CS assessment. On earlier timed sCTA, the predicted proportions of scans with poor collaterals was higher and vice versa. In this data set of highly selected patients with stroke, using a regional CS on sCTA likely allows for the most accurate prediction of functional outcome while on time-resolved CTA, the type of CS did not matter. Patients across all collateral grades benefit from endovascular thrombectomy. sCTA timing independently influenced CS assessment.
Publisher: SAGE Publications
Date: 27-09-2018
Abstract: Intravenous thrombolysis with alteplase remains standard care prior to thrombectomy for eligible patients within 4.5 h of ischemic stroke onset. However, alteplase only succeeds in reperfusing large vessel arterial occlusion prior to thrombectomy in a minority of patients. We hypothesized that tenecteplase is non-inferior to alteplase in achieving reperfusion at initial angiogram, when administered within 4.5 h of ischemic stroke onset, in patients planned to undergo endovascular therapy. EXTEND-IA TNK is an investigator-initiated, phase II, multicenter, prospective, randomized, open-label, blinded-endpoint non-inferiority study. Eligibility requires a diagnosis of ischemic stroke within 4.5 h of stroke onset, pre-stroke modified Rankin Scale≤3 (no upper age limit), large vessel occlusion (internal carotid, basilar, or middle cerebral artery) on multimodal computed tomography and absence of contraindications to intravenous thrombolysis. Patients are randomized to either IV alteplase (0.9 mg/kg, max 90 mg) or tenecteplase (0.25 mg/kg, max 25 mg) prior to thrombectomy. The primary outcome measure is reperfusion on the initial catheter angiogram, assessed as modified treatment in cerebral infarction 2 b/3 or the absence of retrievable thrombus. Secondary outcomes include modified Rankin Scale at day 90 and favorable clinical response (reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0–1) at day 3. Safety outcomes are death and symptomatic intracerebral hemorrhage. ClinicalTrials.gov NCT02388061
Publisher: Wiley
Date: 20-01-2016
DOI: 10.1002/JCC.24267
Abstract: A method is proposed to obtain coefficients and weights of valence bond (VB) determinants from multi configurational wave functions. This reading of the wave functions can apply to ground states as well as excited states. The method is based on projection operators. Both energetic and overlap-based criteria are used to assess the quality of the resulting VB wave function. The approach gives a simple access to a VB rewriting for low-lying states, and it is applied to the allyl cation, to the allyl radical and to the ethene (notably to the V-state). For these states, large overlap between VB and multi reference wave functions are easily obtained. The approach proves to be useful to propose an interpretation of the nature of the V-state of ethene.
Publisher: SAGE Publications
Date: 16-06-2009
DOI: 10.1177/17474930221135730
Abstract: Broadening eligibility criteria has been a focus to increase the generalizability of trial findings. Using upper-limb motor trials conducted early post-stroke as the illustrative domain, we sought to (1) investigate whether the published aim and conclusion statements adequately reflect the generalizability of findings and (2) explore internal validity and feasibility as constraints to achieving generalizability. We systematically applied a conceptual model of a trial s ling process to published literature from systematic review and prospective cross-sectional data. The eligibility criteria reported and used to exclude patients were classified by consensus as related to safety, internal validity, feasibility, or a combination thereof. Categorical data were reported as counts roportions, and continuous data were reported as median (interquartile range (IQR)). Thirty trials ( n = 1638 participants) were included in the published literature and 1013 patients in the prospective data set. Thirty-seven percent of trials did not describe their target population in the aim and conclusion, and 80% did not report all trial screening data. Eligibility criteria related to internal validity were the most common type reported and applied to exclude patients across both data sets. In the prospective data set, 70% of patients were excluded for more than one reason. Key information to support the generalizability of trial findings was insufficiently reported in published upper-limb motor research conducted early post-stroke. Broadening eligibility criteria alone is unlikely to sufficiently improve trial inclusivity due to internal validity constraints. Trials could achieve inclusivity through targeting multiple sub-populations, that in combination, produce clinically relevant results that are applicable to a broader population.
Publisher: Oxford University Press (OUP)
Date: 25-08-2015
Publisher: Georg Thieme Verlag KG
Date: 06-2022
DOI: 10.1055/A-1867-0674
Abstract: Visualization of electron delocalization and aromaticity in some selected arynes, including nonplanar ex les, and their Diels–Alder or dimerization reactions was achieved through multidimensional isotropic magnetic shielding contour maps. These maps showed that arynes are generally less aromatic than the corresponding arenes, and that aromaticity peaks during their reactions when approaching the transition state.
Publisher: BMJ
Date: 02-2022
DOI: 10.1136/BMJOPEN-2021-055461
Abstract: Stroke reperfusion therapies, comprising intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT), are best practice treatments for eligible acute ischemic stroke patients. In Australia, EVT is provided at few, mainly metropolitan, comprehensive stroke centres (CSC). There are significant challenges for Australia’s rural and remote populations in accessing EVT, but improved access can be facilitated by a ‘drip and ship’ approach. TACTICS (Trial of Advanced CT Imaging and Combined Education Support for Drip and Ship) aims to test whether a multicomponent, multidisciplinary implementation intervention can increase the proportion of stroke patients receiving EVT. This is a non-randomised controlled, stepped wedge trial involving six clusters across three Australian states. Each cluster comprises one CSC hub and a minimum of three primary stroke centre (PSC) spokes. Hospitals will work in a hub and spoke model of care with access to a multislice CT scanner and CT perfusion image processing software (MIStar, Apollo Medical Imaging). The intervention, underpinned by behavioural theory and technical assistance, will be allocated sequentially, and clusters will move from the preintervention (control) period to the postintervention period. Proportion of all stroke patients receiving EVT, accounting for clustering. Proportion of patients receiving IVT at PSCs, proportion of treated patients (IVT and/or EVT) with good (modified Rankin Scale (mRS) score 0–2) or poor (mRS score 5–6) functional outcomes and European Quality of Life Scale scores 3 months postintervention, proportion of EVT-treated patients with symptomatic haemorrhage, and proportion of reperfusion therapy-treated patients with good versus poor outcome who presented with large vessel occlusion at spokes. Ethical approval has been obtained from the Hunter New England Human Research Ethics Committee (18/09/19/4.13, HREC/18/HNE/241, 2019/ETH01238). Trial results will be disseminated widely through published manuscripts, conference presentations and at national and international platforms regardless of whether the trial was positive or neutral. ACTRN12619000750189 UTNU1111-1230-4161.
Publisher: SAGE Publications
Date: 23-07-2018
Abstract: Alteplase has been the mainstay of thrombolytic treatment since the National Institutes of Neurological Disorders and Stroke trial was published in 1995. Over recent years, several trials have investigated alternative thrombolytic agents. Tenecteplase, a genetically engineered mutant tissue plasminogen activator, has a longer half-life, allowing single intravenous bolus administration without infusion, is more fibrin specific, produces less systemic depletion of circulating fibrinogen, and is more resistant to plasminogen activator inhibitor compared to alteplase. Tenecteplase is established as the first-line intravenous thrombolytic drug for myocardial infarction, where it has been shown to achieve comparable reperfusion with reduced risk of systemic bleeding in comparison to alteplase. We review the literature on tenecteplase for the treatment of acute ischemic stroke, with a focus on the major completed and ongoing trials. Overall, tenecteplase shows promise for treatment of acute ischemic stroke, both in populations currently eligible for alteplase and also in groups not currently treated with thrombolysis.
Publisher: SAGE Publications
Date: 30-09-2019
Abstract: Intravenous thrombolysis with tenecteplase is more effective than alteplase in achieving substantial reperfusion at initial angiographic assessment and improves functional outcome. However, the optimal dose of tenecteplase remains uncertain. We hypothesized that 0.40 mg/kg tenecteplase is superior to 0.25 mg/kg tenecteplase in achieving reperfusion at initial angiogram, when administered within 4.5 h of ischemic stroke onset, in patients planned to undergo endovascular therapy. EXTEND-IA TNK part 2 is an investigator-initiated, phase II, multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) study. Eligibility requires a diagnosis of ischemic stroke within 4.5 h of stroke onset, pre-stroke modified Rankin Scale (mRS)≤3 (no upper age limit), absence of contraindications to intravenous thrombolysis, and large vessel occlusion (internal carotid, basilar, or middle cerebral artery) on multimodal CT. Patients are randomized to IV tenecteplase at either 0.40 mg/kg (max 40 mg) or 0.25 mg/kg (max 25 mg) prior to thrombectomy. The primary outcome measure is reperfusion on the initial catheter angiogram, assessed as modified Treatment In Cerebral Infarction (mTICI) 2b/3, or the absence of retrievable intracranial thrombus. Secondary outcomes include mRS at day 90 and early neurological improvement (reduction in National Institutes of Health Stroke Scale (NIHSS) by ≥8 points or reaching 0–1) at day 3. Safety outcomes are death and symptomatic intracerebral hemorrhage. Trial registration: ClinicalTrials.gov NCT03340493
Publisher: Wiley
Date: 10-09-2022
DOI: 10.1002/ANA.26491
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: American Chemical Society (ACS)
Date: 05-10-2022
Abstract: Pyrazine-fused 1,2,6,6a-tetrazapentalenes (PyTeAP) are zwitterionic tricyclic compounds exhibiting an original pattern with four consecutive nitrogen atoms. They were obtained by a challenging cyclization through the formation of a N-N bond under thermolytic conditions. Ten derivatives were synthesized, and the original scaffold of PyTeAP was confirmed by single-crystal X-ray diffraction analysis of one derivative. Examination of their photophysical properties in solution revealed blue fluorescence with λ
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2022
DOI: 10.1097/JNN.0000000000000632
Abstract: BACKGROUND: Mobile stroke units (MSUs) are ambulance-based prehospital stroke care services. Through immediate roadside assessment and onboard brain imaging, MSUs provide faster stroke management with improved patient outcomes. Mobile stroke units have enabled the development of expanded scope of practice for stroke nurses however, there is limited published evidence about these evolving prehospital acute nursing roles. AIMS: The aim of this study was to explore the expanded scope of practice of nurses working on MSUs by identifying MSUs with onboard nurses describing the roles and responsibilities, training, and experience of MSU nurses, through a search of the literature and describing 2 international MSU services incorporating nurses from Memphis, Tennessee, and Melbourne, Australia. METHODS: We searched PubMed, CINAHL, and the Joanna Briggs Institute Evidence-Based Practice database using the terms “mobile stroke unit” and “nurse.” Existing MSUs were identified through the PRE-hospital Stroke Treatment Organization to determine models that involved nurses. We describe 2 MSUs involving nurses: one in Memphis and one in Melbourne, led by 2 of our authors. RESULTS: Ninety articles were found describing 15 MSUs however, staffing details were lacking, and it is unknown how many employ nurses. Nine articles described the role of the nurse, but role specifics, training, and expertise were largely undocumented. The MSU in Memphis, the only unit to be staffed exclusively by onboard nurse practitioners, is supported by a neurologist who consults via telephone. The Melbourne MSU plans to trial a nurse-led telemedicine model in the near future. CONCLUSION: We lack information on how many MSUs employ nurses, and the nurses' scope of practice, training, and expertise. Expert stroke nurse practitioners can safely perform many of the tasks undertaken by the onboard neurologist, making a nurse-led telemedicine model an effective and potentially cost-effective model that should be considered for all MSUs.
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: SAGE Publications
Date: 29-03-2021
Abstract: The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide. We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March–31 May 2020) compared with two control three-month periods (immediately preceding and one year prior). Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers. The hospitalization volumes for any stroke, intracranial hemorrhage, and mechanical thrombectomy were 26,699, 4002, and 5191 in the three months immediately before versus 21,576, 3540, and 4533 during the first three pandemic months, representing declines of 19.2% (95%CI, −19.7 to −18.7), 11.5% (95%CI, −12.6 to −10.6), and 12.7% (95%CI, −13.6 to −11.8), respectively. The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/mechanical thrombectomy centers. High-volume COVID-19 centers (−20.5%) had greater declines in mechanical thrombectomy volumes than mid- (−10.1%) and low-volume (−8.7%) centers (p 0.0001). There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions. The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospitalizations, mechanical thrombectomy procedures, and intracranial hemorrhage admission volumes. Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/mechanical thrombectomy volumes.
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: Wiley
Date: 08-01-2020
Abstract: We report a molecular design and concept using π-system elongation and steric effects from helicenes surrounding a triphenylene core toward stable chiral polycyclic aromatic hydrocarbons (PAHs) with a maximal π-distortion to tackle their aromaticity, supramolecular and molecular properties. The selective syntheses, and the structural, conformational and chiroptical properties of two diastereomeric large multi-helicenes of formula C
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.NEUROIMAGE.2014.04.056
Abstract: Understanding structure-function relationships in the brain after stroke is reliant not only on the accurate anatomical delineation of the focal ischemic lesion, but also on previous infarcts, remote changes and the presence of white matter hyperintensities. The robust definition of primary stroke boundaries and secondary brain lesions will have significant impact on investigation of brain-behavior relationships and lesion volume correlations with clinical measures after stroke. Here we present an automated approach to identify chronic ischemic infarcts in addition to other white matter pathologies, that may be used to aid the development of post-stroke management strategies. Our approach uses Bayesian-Markov Random Field (MRF) classification to segment probable lesion volumes present on fluid attenuated inversion recovery (FLAIR) MRI. Thereafter, a random forest classification of the information from multimodal (T1-weighted, T2-weighted, FLAIR, and apparent diffusion coefficient (ADC)) MRI images and other context-aware features (within the probable lesion areas) was used to extract areas with high likelihood of being classified as lesions. The final segmentation of the lesion was obtained by thresholding the random forest probabilistic maps. The accuracy of the automated lesion delineation method was assessed in a total of 36 patients (24 male, 12 female, mean age: 64.57±14.23yrs) at 3months after stroke onset and compared with manually segmented lesion volumes by an expert. Accuracy assessment of the automated lesion identification method was performed using the commonly used evaluation metrics. The mean sensitivity of segmentation was measured to be 0.53±0.13 with a mean positive predictive value of 0.75±0.18. The mean lesion volume difference was observed to be 32.32%±21.643% with a high Pearson's correlation of r=0.76 (p<0.0001). The lesion overlap accuracy was measured in terms of Dice similarity coefficient with a mean of 0.60±0.12, while the contour accuracy was observed with a mean surface distance of 3.06mm±3.17mm. The results signify that our method was successful in identifying most of the lesion areas in FLAIR with a low false positive rate.
Publisher: American Association for Cancer Research (AACR)
Date: 08-2015
DOI: 10.1158/1055-9965.EPI-15-0094
Abstract: Background: Microsatellite instability (MSI) and BRAF mutation status are associated with colorectal cancer survival, whereas the role of body mass index (BMI) is less clear. We evaluated the association between BMI and colorectal cancer survival, overall and by strata of MSI, BRAF mutation, sex, and other factors. Methods: This study included 5,615 men and women diagnosed with invasive colorectal cancer who were followed for mortality (maximum: 14.7 years mean: 5.9 years). Prediagnosis BMI was derived from self-reported weight approximately one year before diagnosis and height. Tumor MSI and BRAF mutation status were available for 4,131 and 4,414 persons, respectively. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) were estimated from delayed-entry Cox proportional hazards models. Results: In multivariable models, high prediagnosis BMI was associated with higher risk of all-cause mortality in both sexes (per 5-kg/m2 HR, 1.10 95% CI, 1.06–1.15), with similar associations stratified by sex (Pinteraction: 0.41), colon versus rectum (Pinteraction: 0.86), MSI status (Pinteraction: 0.84), and BRAF mutation status (Pinteraction: 0.28). In joint models, with MS-stable/MSI-low and normal BMI as the reference group, risk of death was higher for MS-stable/MSI-low and obese BMI (HR, 1.32 P value: 0.0002), not statistically significantly lower for MSI-high and normal BMI (HR, 0.86 P value: 0.29), and approximately the same for MSI-high and obese BMI (HR, 1.00 P value: 0.98). Conclusions: High prediagnosis BMI was associated with increased mortality this association was consistent across participant subgroups, including strata of tumor molecular phenotype. Impact: High BMI may attenuate the survival benefit otherwise observed with MSI-high tumors. Cancer Epidemiol Biomarkers Prev 24(8) 1229–38. ©2015 AACR.
Publisher: American Chemical Society (ACS)
Date: 21-11-2008
DOI: 10.1021/JP803813E
Abstract: A new approach to extract the coefficients and weights of Lewis structures from the Hückel wave function is designed: Hückel-Lewis projection (HL-P). The weights are obtained by projection on overlapping Lewis structures. This straightforward alternative to ab initio approaches is detailed and used on typical cases, including acrolein, allyl radical, pyrrole-like systems, and imidazolylidene. A trust parameter is defined and shown as a guide to retrieve the most important Lewis structures. The emblematic ex les of butadiene and benzene are chosen to illustrate the use of this parameter.
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: 15-05-2022
DOI: 10.5694/MJA2.51520
Publisher: Wiley
Date: 25-07-2022
DOI: 10.1002/ANA.26418
Abstract: This study was undertaken to evaluate functional and safety outcomes for endovascular thrombectomy (EVT) versus medical management (MM) in patients with large vessel occlusion (LVO) and mild neurological deficits, stratified by perfusion imaging mismatch. The pooled cohort consisted of patients with National Institutes of Health Stroke Scale (NIHSS) < 6 and internal carotid artery (ICA), M1, or M2 occlusions from the Extending the Time for Thrombolysis in Emergecy Neurological Deficits - Intra-Arterial (EXTEND-IA) Trial, Tenecteplase vs Alteplase before Endovascular Thrombectomy in Ischemic Stroke (EXTEND-IA TNK) trials Part I/II and prospective data from 15 EVT centers from October 2010 to April 2020. RAPID software estimated ischemic core and mismatch. Patients receiving primary EVT (EVT Of 540 patients, 286 (53%) received EVT Overall, EVT was not associated with improved clinical outcomes in mild strokes due to LVO, and sICH was increased. However, in patients with target mismatch profile, EVT was associated with increased functional independence. Perfusion imaging may be helpful to select mild stroke patients for EVT. ANN NEUROL 2022 :364-378.
Publisher: SAGE Publications
Date: 15-03-2018
Abstract: This review summarizes the current state of knowledge regarding the use of imaging to guide stroke treatment. Brain imaging plays a central role in the diagnosis of stroke and identification of the mechanism of stroke, which is relevant to acute treatment, prognosis, and secondary prevention. The chief potential modalities are computed tomography (CT) and magnetic resonance imaging (MRI). Currently, most imaging occurs in hospital but mobile stroke units have expanded CT brain imaging into the prehospital field. The proven therapies for ischemic stroke are based on achieving reperfusion and the DAWN and DEFUSE 3 trials have now firmly established a need for imaging selection based on estimated ischemic core volume to guide reperfusion decisions in patients beyond 6 h of stroke onset. However, data also indicate that estimated ischemic core volume, in conjunction with patient factors and expected time delay to reperfusion, forms one of the most useful prognostic assessments that could alter decision-making for patients within 6 h. Current trials are also investigating agents that aim to achieve neuroprotection, reduction in edema or prevention of hemorrhagic transformation. Imaging may play a role in identifying patients likely to benefit from this next generation of interventions for stroke patients.
Publisher: Wiley
Date: 2001
DOI: 10.1046/J.1471-4159.2001.00021.X
Abstract: Intracellular inclusions containing alpha-synuclein (alpha SN) are pathognomonic features of several neurodegenerative disorders. Inclusions occur in oligodendrocytes in multiple system atrophy (MSA) and in neurons in dementia with Lewy bodies (DLB) and Parkinson's disease (PD). In order to identify disease-associated changes of alpha SN, this study compared the levels, solubility and molecular weight species of alpha SN in brain homogenates from MSA, DLB, PD and normal aged controls. In DLB and PD, substantial amounts of detergent-soluble and detergent-insoluble alpha SN were detected compared with controls in grey matter homogenate. Compared with controls, MSA cases had significantly higher levels of alpha SN in the detergent-soluble fraction of brain s les from pons and white matter but detergent-insoluble alpha SN was not detected. There was an inverse correlation between buffered saline-soluble and detergent-soluble levels of alpha SN in in idual MSA cases suggesting a transition towards insolubility in disease. The differences in solubility of alpha SN between grey and white matter in disease may result from different processing of alpha SN in neurons compared with oligodendrocytes. Highly insoluble alpha SN is not involved in the pathogenesis of MSA. It is therefore possible that buffered saline-soluble or detergent-soluble forms of alpha SN are involved in the pathogenesis of other alpha SN-related diseases.
Publisher: Springer Berlin Heidelberg
Date: 2004
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.JOCN.2012.10.013
Abstract: Haemorrhagic transformation (HT) is an infrequent but serious complication of intravenous thrombolysis therapy (IVT) for acute ischemic stroke. The hyperdense middle cerebral artery sign (HMCAS) is a possible radiological predictor. We aimed to assess the association between HMCAS and HT in a retrospective study. We included all patients with acute anterior circulation ischaemic stroke who received IVT between October 2007 and December 2011. Baseline characteristics were collected, including demographics, stroke risk factors and stroke type. Presence of HMCAS on baseline CT scans was evaluated. Follow-up CT scans were examined for HT, categorised according to the European Australasian Acute Stroke Study (ECASS) classification. The presence of symptomatic intracerebral haemorrhage (sICH) was defined according to Safe Implementation of Thrombolysis in Stroke Monitoring Study (SITS-MOST) criteria. The association between HT and HMCAS was assessed by univariate and multivariate logistic regression analysis. We included 182 consecutive patients treated with IVT in this study. HMCAS was present in 70 patients (38.5%). Patients with HMCAS had higher baseline National Institutes of Health Stroke Scale scores (p<0.001) and more frequent early ischaemic changes on baseline CT scan (p<0.001) than those without HMCAS. We identified 49 instances (26.9%) of HT in 182 follow-up CT scans. HMCAS was associated with HT in univariate analysis (unadjusted odds ratio [OR]=4.151, 95% confidence interval [CI]: 2.081-8.279, p<0.001) and remained an independent risk factor of HT in multivariate analysis (adjusted OR=2.691, 95% CI: 1.231-5.882, p=0.013). There was no statistically significant difference in the frequency of sICH between the HMCAS group and the non-HMCAS group. We concluded that HMCAS is common in anterior circulation infarction and is independently predictive of HT after thrombolytic therapy.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2021
DOI: 10.1161/STROKEAHA.120.032496
Abstract: Dose articulation is a universal issue of intervention development and testing. In stroke recovery, dose of a nonpharmaceutical intervention appears to influence outcome but is often poorly reported. The challenges of articulating dose in nonpharmacological stroke recovery research include: (1) the absence of specific internationally agreed dose reporting guidelines (2) inadequate conceptualization of dose, which is multidimensional and (3) unclear and inconsistent terminology that incorporates the multiple dose dimensions. To address these challenges, we need a well-conceptualized and consistent approach to dose articulation that can be applied across stroke recovery domains to stimulate critical thinking about dose during intervention development, as well as promote reporting of planned intervention dose versus actually delivered dose. We followed the Design Research Paradigm to develop a framework that guides how to articulate dose, conceptualizes the multidimensional nature and systemic linkages between dose dimensions, and provides reference terminology for the field. Our framework recognizes that dose is multidimensional and comprised of a duration of days that contain in idual sessions and episodes that can be active (time on task) or inactive (time off task), and each in idual episode can be made up of information about length, intensity, and difficulty. Clinical utility of this framework was demonstrated via hypothetical application to preclinical and clinical domains of stroke recovery. The suitability of the framework to address dose articulation challenges was confirmed with an international expert advisory group. This novel framework provides a pathway for better articulation of nonpharmacological dose that will enable transparent and accurate description, implementation, monitoring, and reporting, in stroke recovery research.
Publisher: SAGE Publications
Date: 07-12-2018
Abstract: EXtending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND) is a randomized, multicenter, double-blinded, placebo-controlled phase 3 trial to test the hypothesis of extending the thrombolysis time window to 9 h from stroke onset and in wake-up stroke (WUS) patients. To formulate the detailed statistical analysis plan for the EXTEND trial prior to database lock. This statistical analysis plan is based on the published and registered EXTEND trial protocol and is developed by the blinded steering committee and management team. The developed EXTEND statistical analysis plan is transparent, verifiable, and predetermined before the database lock. It is consistent with reporting standards for clinical trials and provides for clear and open reporting. Publication of a statistical analysis plan serves to reduce potential trial analysis and reporting bias and outlines pre-specified analyses to quantify the benefits and harms of extending the thrombolysis time window to 9 h from stroke onset and in wake-up stroke patients. Trial registration: ClinicalTrials.gov number NCT00887328 registered 23/Apr/2009 and NCT01580839 (EXTEND International) registered 19/Apr/2012
Publisher: American Society of Neuroradiology (ASNR)
Date: 17-04-2014
DOI: 10.3174/AJNR.A3931
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2014
DOI: 10.1161/STROKEAHA.114.006694
Abstract: Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) has been used to estimate diffusion-weighted imaging (DWI) lesion volume in acute stroke. We aimed to assess correlations of DWI-ASPECTS with lesion volume in different middle cerebral artery (MCA) subregions and reproduce existing ASPECTS thresholds of a malignant profile defined by lesion volume ≥100 mL. We analyzed data of patients with MCA stroke from a prospective observational study of DWI and fluid-attenuated inversion recovery in acute stroke. DWI-ASPECTS and lesion volume were calculated. The population was ided into subgroups based on lesion localization (superficial MCA territory, deep MCA territory, or both). Correlation of ASPECTS and infarct volume was calculated, and receiver-operating characteristics curve analysis was performed to identify the optimal ASPECTS threshold for ≥100-mL lesion volume. A total of 496 patients were included. There was a significant negative correlation between ASPECTS and DWI lesion volume ( r =–0.78 P .0001). With regards to lesion localization, correlation was weaker in deep MCA region ( r =–0.19 P =0.038) when compared with superficial ( r =–0.72 P .001) or combined superficial and deep MCA lesions ( r =–0.72 P .001). Receiver-operating characteristics analysis revealed ASPECTS≤6 as best cutoff to identify ≥100-mL DWI lesion volume however, positive predictive value was low (0.35). ASPECTS has limitations when lesion location is not considered. Identification of patients with malignant profile by DWI-ASPECTS may be unreliable. ASPECTS may be a useful tool for the evaluation of noncontrast computed tomography. However, if MRI is used, ASPECTS seems dispensable because lesion volume can easily be quantified on DWI maps.
Publisher: Massachusetts Medical Society
Date: 26-04-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2021
DOI: 10.1161/STROKEAHA.120.032935
Abstract: Benefit of early endovascular treatment (EVT) for ischemic stroke varies considerably among patients. The MR PREDICTS decision tool, derived from MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), predicts outcome and treatment benefit based on baseline characteristics. Our aim was to externally validate and update MR PREDICTS with data from international trials and daily clinical practice. We used in idual patient data from 6 randomized controlled trials within the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration to validate the original model. Then, we updated the model and performed a second validation with data from the observational MR CLEAN Registry. Primary outcome was functional independence (defined as modified Rankin Scale score 0–2) 3 months after stroke. Treatment benefit was defined as the difference between the probability of functional independence with and without EVT. Discriminative performance was evaluated using a concordance (C ) statistic. We included 1242 patients from HERMES (633 assigned to EVT, 609 assigned to control) and 3156 patients from the MR CLEAN Registry (all of whom underwent EVT within 6.5 hours). The C -statistic for functional independence was 0.74 (95% CI, 0.72–0.77) in HERMES and, after model updating, 0.80 (0.78–0.82) in the Registry. Median predicted treatment benefit of routinely treated patients (Registry) was 10.3% (interquartile range, 5.8%–14.4%). Patients with low ( %) predicted treatment benefit (n=135/3156 [4.3%]) had low rates of functional independence, irrespective of reperfusion status, suggesting potential absence of treatment benefit. The updated model was made available online for clinicians and researchers at www.mrpredicts.com . Because of the substantial treatment effect and small potential harm of EVT, most patients arriving within 6 hours at an endovascular-capable center should be treated regardless of their clinical characteristics. MR PREDICTS can be used to support clinical judgement when there is uncertainty about the treatment indication, when resources are limited, or before a patient is to be transferred to an endovascular-capable center.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2012
DOI: 10.1161/STROKEAHA.112.660548
Abstract: Perfusion imaging has the potential to select patients most likely to respond to thrombolysis. We tested the correspondence of computed tomography perfusion (CTP)-derived mismatch with contemporaneous perfusion-diffusion magnetic resonance imaging (MRI). Acute ischemic stroke patients 3 to 6 hours after onset had CTP and perfusion-diffusion MRI within 1 hour, before thrombolysis. Relative cerebral blood flow (relCBF) and time to peak of the deconvolved tissue residue function (Tmax) were calculated. The diffusion lesion (diffusion-weighted imaging) was registered to the CTP slabs and manually outlined to its maximal visual extent. Volumetric accuracy of CT-relCBF infarct core (compared with diffusion-weighted imaging) was tested. To reduce false-positive low CBF regions, relCBF core was restricted to voxels within a relative time-to-peak (relTTP) seconds for lesion region of interest. The MR-Tmax seconds perfusion lesion was automatically segmented and registered to CTP. Receiver-operating characteristic analysis determined the optimal CT-Tmax threshold to match MR-Tmax seconds. Agreement of these CT parameters with MR perfusion-diffusion mismatch in coregistered slabs was assessed (mismatch ratio .2, absolute mismatch mL, infarct core mL). In analysis of 49 patients (mean onset to CT, 213 minutes mean CT to MR, 31 minutes), constraining relCBF % within the automated relTTP perfusion lesion region of interest reduced the median magnitude of volumetric error (vs diffusion-weighted imaging) from 47.5 mL to 15.8 mL ( P .001). The optimal CT-Tmax threshold to match MR-Tmax seconds was 6.2 seconds (95% confidence interval, 5.6–7.3 seconds sensitivity, 91% specificity, 70% area under the curve, 0.87). Using CT-Tmax seconds “penumbra” and relTTP-constrained relCBF “core,” CT-based and MRI-based mismatch status was concordant in 90% (kappa=0.80). Quantitative CTP mismatch classification using relCBF and Tmax is similar to perfusion-diffusion MRI. The greater accessibility of CTP may facilitate generalizability of mismatch-based selection in clinical practice and trials.
Publisher: American Medical Association (AMA)
Date: 2012
DOI: 10.1001/ARCHNEUROL.2011.232
Abstract: Imaging is used as a surrogate for clinical outcome in early-phase stroke trials. Assessment of infarct growth earlier than the standard 90 days used for clinical end points may be equally accurate and more practical. To compare assessment of the effect of reperfusion therapies using 24-hour vs day 90 magnetic resonance imaging. Infarct volume was assessed on diffusion-weighted imaging (DWI) at baseline and 24 hours after stroke onset and on fluid-attenuated inversion recovery images at day 90. The DWI and fluid-attenuated inversion recovery lesions were manually outlined by 2 independent raters, and the volumes were averaged. Interrater consistency was assessed using the median difference in lesion volume between raters. Referral center. Patients Imaging data were available for 83 patients 77 of these patients received thrombolysis. Infarct volume at 24 hours and 90 days. The 24-hour DWI infarct volume had a strong linear correlation with day 90 fluid-attenuated inversion recovery infarct volume (r = 0.98, 95% confidence interval, 0.97-0.99). Recanalization had a significant effect on infarct evolution between baseline and 24 hours but not between 24 hours and day 90. Infarct growth from baseline was significantly reduced by recanalization, whether assessed at 24 hours or day 90. Infarct volume at either time point predicted functional outcome independent of age and baseline stroke severity. Interrater agreement was better for DWI than fluid-attenuated inversion recovery (1.4 mL [8%] vs 1.8 mL [17%] P = .002). Assessment of final infarct volume using DWI at 24 hours captures the effect of reperfusion therapies on infarct growth and predicts functional outcome similarly to imaging at day 90. This has the potential to reduce loss to follow-up in trials and may add early prognostic information in clinical practice.
Publisher: Massachusetts Medical Society
Date: 06-04-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2021
DOI: 10.1161/STROKEAHA.121.036537
Abstract: The coronavirus disease 2019 (COVID-19) pandemic has presented unique challenges to stroke care and research internationally. In particular, clinical trials in stroke are vulnerable to the impacts of the pandemic at multiple stages, including design, recruitment, intervention, follow-up, and interpretation of outcomes. A carefully considered approach is required to ensure the appropriate conduct of stroke trials during the pandemic and to maintain patient and participant safety. This has been recently addressed by the International Council for Harmonisation which, in November 2019, released an addendum to the Statistical Principles for Clinical Trials guidelines entitled Estimands and Sensitivity Analysis in Clinical Trials. In this article, we present the International Council for Harmonisation estimand framework for the design and conduct of clinical trials, with a specific focus on its application to stroke clinical trials. This framework aims to align the clinical and scientific objectives of a trial with its design and end points. It also encourages the prospective consideration of potential postrandomization intercurrent events which may occur during a trial and either impact the ability to measure an end point or its interpretation. We describe the different categories of such events and the proposed strategies for dealing with them, specifically focusing on the COVID-19 pandemic as a source of intercurrent events. We also describe potential practical impacts posed by the COVID-19 pandemic on trials, health systems, study groups, and participants, all of which should be carefully reviewed by investigators to ensure an adequate practical and statistical strategy is in place to protect trial integrity. We provide ex les of the implementation of the estimand framework within hypothetical stroke trials in intracerebral hemorrhage and stroke recovery. While the focus of this article is on COVID-19 impacts, the strategies and principles proposed are well suited for other potential events or issues, which may impact clinical trials in the field of stroke.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2022
DOI: 10.1161/STROKEAHA.122.039774
Abstract: Age and infarct volume are strong predictors of outcome in patients with ischemic stroke who underwent endovascular therapy (EVT). We aimed to investigate the impact of ischemic core volume (ICV) on stroke outcome after EVT in elderly. Using the HERMES (Highly Effective Reperfusion Using Multiple Endovascular Devices) collaboration, a patient-level meta-analysis of 7 randomized trials in which patients were enrolled from December 2010 to April 2015) dataset, we categorized patients into those aged and ≥75 years. ICV was calculated on computed tomography perfusion or magnetic resonance diffusion-weighted imaging. The association between ICV and the benefit of EVT over best medical treatment on outcome (modified Rankin Scale [mRS] at 90 days) and an ICV threshold for high likelihood (≥90%) of very poor outcome (mRS score ≥5) after EVT were investigated. A total of 899 patients who had baseline ICV data, 247 patients aged ≥75 years, of which 118 were randomized in the EVT arm. Patients aged ≥75 years required smaller ICV to achieve mRS score ≤3 than those aged years in the EVT arm (median 10.7 mL versus 23.9 mL, P .001). In patients aged ≥75 years, modeling of outcome in both treatment arms revealed potential loss of effect for EVT at ICV of ≥50 mL or ≥85 mL for achieving mRS score ≤3 or ≤4, respectively. Treatment effect of EVT was significant in ICV mL for mRS ≤3 (odds ratio 2.38, 95% confidence interval 1.35–4.22). ICV ≥132 mL was a threshold for high likelihood of very poor outcome after EVT. However, EVT still predicted at least 30% rate of mRS ≤3 at 150 mL ICV if near-complete or complete reperfusion was achieved. Baseline ICV has an impact on stroke outcome after EVT in the elderly, but elderly patients with large ICV may still benefit from EVT if near-complete or complete reperfusion is achieved. Young patients seem to benefit from EVT regardless of ICV status.
Publisher: SAGE Publications
Date: 24-08-2022
DOI: 10.1177/17474930221120345
Abstract: Uncertainty exists over the optimal level of blood pressure (BP) after mechanical thrombectomy (MT) for acute ischemic stroke (AIS). We aim to determine the effectiveness and safety of intensive BP-lowering following MT reperfusion of large-vessel occlusion (LVO)-related AIS. The second ENhanced Control of Hypertension ANd Thrombolysis strokE stuDy (ENCHANTED2) is an investigator-initiated, multicenter, prospective, randomized, open, blinded-endpoint (PROBE) trial of intensive systolic BP (SBP) control in reperfused (extended treatment in cerebral infarction (eTICI) classification 2b/2c/3) LVO-AIS patients with persistent hypertension (SBP ⩾ 140 mmHg) at 60+ sites in China, and Australia and the United Kingdom. Eligible patients are centrally randomly allocated to more- (target SBP ⩽ 120 mmHg within 1 h) or less-intensive (target SBP 140–180 mmHg) BP management, to be maintained for 72 h. Primary outcome is an ordinal shift analysis of scores on the modified Rankin scale (mRS) at 90 days. S le size of 2257 patients provides 90% power to detect a 6.5% absolute reduction in poor outcome from more-intensive BP-lowering using ordinal logistic regression. Recruitment started in China in July 2020. At a meeting of the independent Data and Safety Monitoring Board in March 2022 to review primary outcome data available for 347 patients, they recommended suspension of recruitment due to safety concerns in the more-intensive group which was implemented by the Trial Steering Committee (TSC) with 817 randomized patients only in China. The TSC then stopped recruitment after the safety concerns persisted on further review of the data in June 2022. The TSC will make a decision on restarting the trial with modification of the protocol when the results are made public. ENCHANTED2 will provide further randomized evidence on the role of intensive BP-lowering after reperfusion in MT-treated AIS patients. ClinicalTrials.gov NCT04140110 registered 25 October 2019.
Publisher: SAGE Publications
Date: 14-06-2020
Abstract: The Melbourne Mobile Stroke Unit (MSU) is the first Australian service to provide prehospital acute stroke treatment, including thrombolysis and facilitated triage for endovascular thrombectomy. To estimate the cost-effectiveness of the MSU during the first full year of operation compared with standard ambulance and hospital stroke care pathways (standard care). The costs and benefits of the Melbourne MSU were estimated using an economic simulation model. Operational costs and service utilization data were obtained from the MSU financial and patient tracking reports. The health benefits were estimated as disability-adjusted life years (DALYs) avoided using local data on reperfusion therapy and estimates from the published literature on their effectiveness. Costs were presented in Australian dollars. The robustness of results was assessed using multivariable (model inputs varied simultaneously: 10,000 Monte Carlo iterations) and various one-way sensitivity analyses. In 2018, the MSU was dispatched to 1244 patients during 200 days of operation. Overall, 167 patients were diagnosed with acute ischemic stroke, and 58 received thrombolysis, endovascular thrombectomy, or both. We estimated 27.94 DALYs avoided with earlier access to endovascular thrombectomy (95% confidence interval (CI) 15.30 to 35.93) and 16.90 DALYs avoided with improvements in access to thrombolysis (95% CI 9.05 to 24.68). The MSU was estimated to cost an additional $30,982 per DALY avoided (95% CI $21,142 to $47,517) compared to standard care. There is evidence that the introduction of MSU is cost-effective when compared with standard care due to earlier provision of reperfusion therapies.
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.JOCN.2014.03.029
Abstract: The risk of thrombolysis in patients taking novel anticoagulants remains unclear. We describe a patient with a large acute ischaemic stroke, who had a low calibrated anti-factor Xa level, who safely received thrombolysis 15-17 hours after standard dose rivaroxaban without subsequent intracerebral haemorrhage.
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: Springer Science and Business Media LLC
Date: 28-05-2022
Publisher: SAGE Publications
Date: 17-07-2019
Abstract: Administration of intravenous idarucizumab to reverse dabigatran anticoagulation prior to thrombolysis for patients with acute ischemic stroke has been previously described, but not in the prehospital setting. The speed and predictability of idarucizumab reversal is well suited to prehospital treatment in a mobile stroke unit and allows patients with recent dabigatran intake to access reperfusion therapy. To describe feasibility of prehospital idarucizumab administration prior to thrombolysis on the Melbourne mobile stroke unit. The Melbourne mobile stroke unit is a specialized stroke ambulance servicing central metropolitan Melbourne, Australia and provides prehospital assessment, scanning and treatment with an integrated CT scanner and multidisciplinary stroke team. All cases were identified through the mobile stroke unit treatment registry since launch in November 2017. Of a total of n = 20 thrombolysis cases in the first 4 months of operation, three patients (15%) received intravenous idarucizumab 5 g for dabigatran reversal prior to thrombolysis. Mean time between idarucizumab administration and thrombolysis was approximately 10 minutes. Two of the three patients were shown to have large vessel occlusion on CTA in the mobile stroke unit and proceeded to endovascular thrombectomy. At 24 hours, only one patient had a small amount of asymptomatic petechial hemorrhage on follow-up imaging. All patients demonstrated substantial neurological recovery and were discharged to inpatient rehabilitation. Rapid treatment with prehospital administration of idarucizumab prior to thrombolysis using a mobile stroke unit is feasible and facilitates hyperacute treatment.
Publisher: Wiley
Date: 13-01-2023
DOI: 10.1111/IMJ.15999
Abstract: Cerebral amyloid angiopathy (CAA) is a disease with several clinical manifestations. It is characterised by amyloid‐beta deposition in cerebral blood vessels, making them prone to bleeding. The incidence of CAA increases with age and may be associated or co‐exist with intraparenchymal neurodegenerative proteinopathies, which makes it an increasingly relevant condition for adult physicians in all areas of medical practice. The vast majority of cases of CAA are sporadic with a small minority of familial cases. CAA is asymptomatic in many older adults but increases the risk of fatal intracerebral or subarachnoid haemorrhage. We review the existing literature on CAA and summarise the key findings. We specifically explore clinical challenges relevant to CAA, particularly in diagnosis, management of intracranial haemorrhage and management of concurrent medical conditions.
Publisher: American Chemical Society (ACS)
Date: 10-07-2023
DOI: 10.1021/JACS.3C05415
Publisher: Springer Science and Business Media LLC
Date: 27-03-2014
Publisher: SAGE Publications
Date: 04-09-2014
DOI: 10.1111/IJS.12364
Abstract: : Developing improved methods for analysis of the modified Rankin Scale (mRS) remains a critical issue for the stroke research community. A recently proposed permutation-based approach is assumption-free and easily interpretable but computationally intensive and does not provide confidence intervals to quantify the precision of the effect size estimate. We aimed to develop a method to overcome these limitations. : We propose a procedure using generalized odds ratios to estimate the odds that a patient who received the investigational treatment will have a better outcome than a patient receiving standard treatment. This approach was validated against the permutation method using hypothetical clinical trial scenarios of neuroprotective effect, early recanalization effect, late recanalization effect, and random benefit. : The generalized odds ratio approach had strong agreement with the permutation approach provided s le size was patients per treatment arm. Simulation established that the confidence intervals generated were accurate. Ignoring patient pairs with tied mRS scores overestimates the treatment effect compared with splitting tied mRS scores. : In addition to all the advantages of the recently proposed permutation-based approach, our method generates confidence intervals without the need for intensive computational power. The resulting generalized odds ratios are particularly suitable for inclusion in meta-analyses and have a simple and intuitive connection with the number-needed-to-treat measure.
Publisher: S. Karger AG
Date: 2017
DOI: 10.1159/000479707
Abstract: b i Background: /i /b Alberta Stroke Program Early CT Score (ASPECTS) assesses early ischemic change on non-contrast CT (NCCT). We hypothesised that assessing ASPECTS regions on CT Perfusion (CTP) rather than NCCT would improve inter-rater agreement and prognostic accuracy, particularly in patients presenting early after stroke onset. b i Methods: /i /b Ischemic stroke patients treated with intravenous alteplase from 2009 to 2014 at our institution were included in this study. Inter-rater agreement and prognostic accuracy of ASPECTS across modalities were analysed by the time between stroke onset and initial NCCT, dichotomized 1st quartile versus quartiles 2-4, referred to as epochs. ASPECTS was assessed by 2 independent raters, blinded to stroke onset time, with agreement determined by weighted kappa (& #x03BA sub w /sub ). Prognostic accuracy for favourable outcome (modified Rankin Scale 0-2) was assessed using the receiver-operating characteristic analysis. b i Results: /i /b A total of 227 participants were included. There was significant time-by-CT modality interaction for ASPECTS, i /i 0.0001. The inter-rater agreement of ASPECTS on NCCT significantly increased as onset to CT time increased (& #x03BA sub w /sub epoch 1 = 0.76 vs. & #x03BA sub w /sub epoch 2-4 = 0.89, i /i = 0.04), whereas agreement using CTP parameters was stable across epochs. Inter-rater agreement for CTP-ASPECTS was significantly higher than NCCT in early epoch: Tmax & #x03BA sub w /sub = 0.96, i /i = 0.002 cerebral blood volume (CBV) & #x03BA sub w /sub = 0.95, i /i = 0.003 cerebral blood flow (CBF) & #x03BA sub w /sub = 0.94, i /i = 0.006, with no differences in the later epochs. Prognostic accuracy of ASPECTS on NCCT in epoch 1 were (area under the ROC curves [AUC] = 0.52, 95% CI 0.48-0.56), CBV (AUC = 0.55, 95% CI 0.42-0.69, CBF (AUC = 0.58, 95% CI 0.46-0.71) and Tmax (AUC = 0.62, 95% CI 0.49-0.75), i /i = 0.46 between modalities. b i Conclusions: /i /b CTP can improve reliability when assessing the extent of ischemic changes, particularly in patients imaged early after stroke onset.
Publisher: Wiley
Date: 15-10-2013
DOI: 10.1111/CNS.12168
Publisher: SAGE Publications
Date: 15-10-2022
DOI: 10.1177/17474930221125993
Abstract: In China, disparities in the quality of stroke care still exist and implementing quality improvement is still a challenge. The aim of the study was to determine whether the intervention by Shanghai Stroke Service System (4S) has helped improve adherence to stroke care guidelines and patient outcome. The 4S is a regional stroke network with real-time data extraction among its 61 stroke centers in Shanghai. A total of 11 key performance indicators (KPIs) were evaluated. The primary outcomes were a composite measure and an all-or-none measure of adherence to 11 KPIs. The secondary outcomes were length of hospital stay and in-hospital mortality. The study enrolled 92,395 patients (mean age 69.0 ± 12.5 years, 65.2% men) with acute ischemic stroke hospitalized within 7 days of onset in Shanghai from January 2015 to December 2020. More patients received guideline recommended care between 2018 and 2020 than those between 2015 and 2017 (composite measure 87.1% vs 83.6% absolute difference 2.9%, 95% confidence interval (CI) = [2.7%, 3.2%], p 0.001 all-or-none measure 49.2% vs 44.8% patients absolute difference 3.5%, 95% CI = [2.7%, 4.2%], p 0.001). Further analysis of in idual KPIs showed an absolute increase in six KPIs ranging from 3.4% to 8.9% (p 0.001 for all comparisons). Compared with 2015–2017, hospital length of stay was shorter (10.95 vs 11.90 days absolute difference –1.08, 95% CI = [–1.18, –0.99], p 0.001), and in-hospital mortality was significantly reduced (risk ratio (RR) = 0.88, 95% CI = [0.79, 0.98], p = 0.01) in 2018–2020. The 4S intervention was associated with increased adherence to the stroke care guidelines, which further translated to improved clinical outcomes. ClinicalTrials.gov identifier: NCT02735226.
Publisher: SAGE Publications
Date: 04-01-2011
DOI: 10.1111/J.1747-4949.2010.00545.X
Abstract: Central retinal artery occlusion is a stroke of the eye caused by a blockage of its main blood supply by platelet-fibrin clot. Systemic thrombolysis has been successful in restoring perfusion to ischaemic tissue by fibrin-platelet clot lysis in ischaemic stroke and myocardial infarction. Several open-label studies have demonstrated efficacy of thrombolysis in the treatment of central retinal artery occlusion, with up to 60–70% of treated subjects experiencing an improvement in visual acuity. Most of these are given intraarterially, which is an invasive procedure and not widely applicable to all treatment centres. An alternative is the intravenous infusion of tissue plasminogen activator using existing stroke thrombolysis protocols. A systematic review of all observational studies of intravenous tissue plasminogen activator in acute central retinal artery occlusion showed that 48·5% of subjects had a four line or more visual acuity improvement with an acceptable rate of haemorrhagic complications, creating the equipoise necessary to conduct a randomised controlled trial. To determine the efficacy of intravenous thrombolysis in acute treatment of central retinal artery occlusion. A phase II, placebo-controlled, double-blind, randomised controlled trial comparing intravenous tissue plasminogen activator at 0·9 mg/kg to placebo (normal saline) 100 ml in a 1 : 1 block randomisation. The primary outcome measure is an improvement of three lines or more on the Snellen visual acuity chart, which signifies a doubling of the visual angle.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2020
DOI: 10.1161/STROKEAHA.120.029666
Abstract: Tenecteplase improved functional outcomes and reduced the requirement for endovascular thrombectomy in ischemic stroke patients with large vessel occlusion in the EXTEND-IA TNK randomized trial. We assessed the cost-effectiveness of tenecteplase versus alteplase in this trial. Post hoc within-trial economic analysis included costs of index emergency department and inpatient stroke hospitalization, rehabilitation/subacute care, and rehospitalization due to stroke within 90 days. Sources for cost included key study site complemented by published literature and government websites. Quality-adjusted life-years were estimated using utility scores derived from the modified Rankin Scale score at 90 days. Long-term modeled cost-effectiveness analysis used a Markov model with 7 health states corresponding to 7 modified Rankin Scale scores. Probabilistic sensitivity analyses were performed. Within the 202 patients in the randomized controlled trial, total cost was nonsignificantly lower in the tenecteplase-treated patients (40 997 Australian dollars [AUD]) compared with alteplase-treated patients (46 188 AUD) for the first 90 days( P =0.125). Tenecteplase was the dominant treatment strategy in the short term, with similar cost (5412 AUD [95% CI, −13 348 to 2523] P =0.181) and higher benefits (0.099 quality-adjusted life-years [95% CI, 0.001–0.1967] P =0.048), with a 97.4% probability of being cost-effective. In the long-term, tenecteplase was associated with less additional lifetime cost (96 357 versus 106 304 AUD) and greater benefits (quality-adjusted life-years, 7.77 versus 6.48), and had a 100% probability of being cost-effective. Both deterministic sensitivity analysis and probabilistic sensitivity analyses yielded similar results. Both within-trial and long-term economic analyses showed that tenecteplase was highly likely to be cost-effective for patients with acute stroke before thrombectomy. Recommending the use of tenecteplase over alteplase could lead to a cost saving to the healthcare system both in the short and long term. URL: www.clinicaltrials.gov . Unique identifier: NCT02388061.
Publisher: Wiley
Date: 30-11-2023
DOI: 10.1002/ANA.26547
Abstract: Tenecteplase improves reperfusion compared to alteplase in patients with large vessel occlusions. To determine whether this improvement varies across the spectrum of thrombolytic agent to reperfusion assessment times, we performed a comparative analysis of tenecteplase and alteplase reperfusion rates. Patients with large vessel occlusion and treatment with thrombolysis were pooled from the Melbourne Stroke Registry, and the EXTEND‐IA and EXTEND‐IA TNK trials. The primary outcome, thrombolytic‐induced reperfusion, was defined as the absence of retrievable thrombus or % reperfusion at imaging reassessment. We compared the treatment effect of tenecteplase and alteplase, accounting for thrombolytic to assessment exposure times, via Poisson modeling. We compared 90‐day outcomes of patients who achieved reperfusion with a thrombolytic to patients who achieved reperfusion via endovascular therapy using ordinal logistic regression. Among 893 patients included in the primary analysis, thrombolytic‐induced reperfusion was observed in 184 (21%) patients. Tenecteplase was associated with higher rates of reperfusion (adjusted incidence rate ratio [aIRR] = 1.50, 95% confidence interval [CI] = 1.09–2.07, p = 0.01). Findings were consistent in patient subgroups with first segment (aIRR = 1.41, 95% CI = 0.93–2.14) and second segment (aIRR = 2.07, 95% CI = 0.98–4.37) middle cerebral artery occlusions. Increased thrombolytic to reperfusion assessment times were associated with reperfusion (tenecteplase: adjusted risk ratio [aRR] = 1.08 per 15 minutes, 95% CI = 1.04–1.13 vs alteplase: aRR = 1.06 per 15 minutes, 95% CI = 1.00–1.13). No significant treatment‐by‐time interaction was observed ( p = 0.87). Reperfusion via thrombolysis was associated with improved 90‐day modified Rankin Scale scores (adjusted common odds ratio = 2.15, 95% CI = 1.54–3.01) compared to patients who achieved reperfusion following endovascular therapy. Tenecteplase, compared to alteplase, increases prethrombectomy reperfusion, regardless of the time from administration to reperfusion assessment. Prethrombectomy reperfusion is associated with better clinical outcomes. ANN NEUROL 2023 :489–499
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 22-10-2020
DOI: 10.1212/WNL.0000000000011083
Abstract: To investigate whether certain patient, acute care, or primary care factors are associated with medication initiation and discontinuation in the community after stroke or TIA. This is a retrospective cohort study using prospective data on adult patients with first-ever acute stroke/TIA from the Australian Stroke Clinical Registry (April 2010 to June 2014), linked with nationwide medication dispensing and Medicare claims data. Medication users were those with ≥1 dispensing in the year postdischarge. Discontinuation was assessed among medication users and defined as having no medication supply for ≥90 days in the year postdischarge. Multivariable competing risks regression, accounting for death during the observation period, was conducted to investigate factors associated with time to medication discontinuation. Among 17,980 registry patients with stroke/TIA, 91.4% were linked to administrative datasets. Of these, 9,817 adults with first-ever stroke/TIA were included (45.4% female, 47.6% aged ≥75 years, and 11.4% intracerebral hemorrhage). While most patients received secondary prevention medications (79.3% antihypertensive, 81.8% antithrombotic, and 82.7% lipid-lowering medication), between one-fifth and one-third discontinued treatment over the subsequent year postdischarge (20.9% antihypertensive, 34.1% antithrombotic, and 28.5% lipid-lowering medications). Prescription at hospital discharge (sub–hazard ratio [SHR] 0.70 95% confidence interval [CI] 0.62–0.79), quarterly contact with a primary care physician (SHR 0.62 95% CI 0.57–0.67), and prescription by a specialist physician (SHR 0.87 95% CI 0.77–0.98) were all inversely associated with antihypertensive discontinuation. Patterns of use of secondary prevention medications after stroke/TIA are not optimal, with many survivors discontinuing treatment within 1 year postdischarge. Improving postdischarge care for patients with stroke/TIA is needed to minimize unwarranted discontinuation.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2022
DOI: 10.1161/STROKEAHA.122.040480
Abstract: Endovascular thrombectomy (EVT) access in remote areas is limited. Preliminary data suggest that long distance transfers for EVT may be beneficial however, the magnitude and best imaging strategy at the referring center remains uncertain. We hypothesized that patients transferred miles would benefit from EVT, achieving rates of functional independence (modified Rankin Scale [mRS] score of 0–2) at 3 months similar to those patients treated at the comprehensive stroke center in the randomized EVT extended window trials and that the selection of patients with computed tomography perfusion (CTP) at the referring site would be associated with ordinal shift toward better outcomes on the mRS. This is a retrospective analysis of patients transferred from 31 referring hospitals miles (measured by the most direct road distance) to 9 comprehensive stroke centers in Australia and New Zealand for EVT consideration (April 2016 through May 2021). There were 131 patients the median age was 64 [53–74] years and the median baseline National Institutes of Health Stroke Scale score was 16 [12–22]. At baseline, 79 patients (60.3%) had noncontrast CT+CT angiography, 52 (39.7%) also had CTP. At the comprehensive stroke center, 114 (87%) patients underwent cerebral angiography, and 96 (73.3%) proceeded to EVT. At 3 months, 62 patients (48.4%) had an mRS score of 0 to 2 and 81 (63.3%) mRS score of 0 to 3. CTP selection at the referring site was not associated with better ordinal scores on the mRS at 3 months (mRS median of 2 [1–3] versus 3 [1–6] in the patients selected with noncontrast CT+CT angiography, P =0.1). Nevertheless, patients selected with CTP were less likely to have an mRS score of 5 to 6 (odds ratio 0.03 [0.01–0.19] P .01). In selected patients transferred miles, there was a benefit for EVT, with outcomes similar to those treated in the comprehensive stroke center in the EVT extended window trials. Remote hospital CTP selection was not associated with ordinal mRS improvement, but was associated with fewer very poor 3-month outcomes.
Publisher: Springer International Publishing
Date: 2013
Publisher: S. Karger AG
Date: 2010
DOI: 10.1159/000316886
Abstract: i Background: /i The reasons for worse outcome following ischemic stroke in patients with atrial fibrillation (AF) remain unclear. We aimed to elucidate the pathophysiological determinants of poorer stroke outcome in patients with AF using systematic MRI data from the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET). i Methods: /i Comparisons of infarct size, hypoperfusion volume, infarct growth, arterial occlusion, recanalization, reperfusion, hemorrhagic transformation and stroke severity were made between patients with and without AF enrolled in the EPITHET study. i Results: /i AF was present in 42 of 101 patients. At baseline, AF patients were older (79 vs. 73 years, p = 0.02), had more severe neurological impairment (National Institutes of Health Stroke Scale score 16 vs. 11, p = 0.006), larger infarcts (29 vs. 15 ml, p = 0.04) and greater volumes of more severe hypoperfusion (T sub max /sub ≧8 s, perfusion-weighted imaging volume 70 vs. 43 ml, p = 0.01) compared to patients without AF. There were no significant differences in arterial occlusion site, infarct growth, recanalization or reperfusion. At outcome, AF patients had larger infarcts (52 vs. 16 ml, p = 0.05), more severe hemorrhagic transformation (29 vs. 5%, p = 0.002 for parenchymal hematomas), greater disability (modified Rankin Scale score 4 vs. 3, p = 0.03) and higher mortality rates (31 vs. 12%, p = 0.04). AF was an independent predictor of parenchymal hematoma (OR = 6.90, 95% CI = 1.57–30.25), but not mortality (OR = 2.56, 95% CI = 0.83–7.85). i Conclusions: /i Patients with AF have worse clinical and imaging outcomes following ischemic stroke. This study suggests that the adverse effect of AF is due to greater volumes of more severely hypoperfused tissue, leading to larger infarct size and greater risk of severe hemorrhagic transformation.
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.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-03-2021
DOI: 10.1212/WNL.0000000000011520
Abstract: To investigate the efficacy of tenecteplase (TNK), a genetically modified variant of alteplase with greater fibrin specificity and longer half-life than alteplase, prior to endovascular thrombectomy (EVT) in patients with basilar artery occlusion (BAO). To determine whether TNK is associated with better reperfusion rates than alteplase prior to EVT in BAO, clinical and procedural data of consecutive patients with BAO from the Basilar Artery Treatment and Management (BATMAN) registry and the Tenecteplase vs Alteplase before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK) trial were retrospectively analyzed. Reperfusion % or absence of retrievable thrombus at the time of the initial angiogram was evaluated. We included 110 patients with BAO treated with IV thrombolysis prior to EVT (mean age 69 [SD 14] years median NIH Stroke Scale score 16 [interquartile range (IQR) 7–32]). Nineteen patients were thrombolysed with TNK (0.25 mg/kg or 0.40 mg/kg) and 91 with alteplase (0.9 mg/kg). Reperfusion % occurred in 26% (n = 5/19) of patients thrombolysed with TNK vs 7% (n = 6/91) thrombolysed with alteplase (risk ratio 4.0, 95% confidence interval 1.3–12 p = 0.02), despite shorter thrombolysis to arterial puncture time in the TNK-treated patients (48 [IQR 40–71] minutes) vs alteplase-treated patients (110 [IQR 51–185] minutes p = 0.004). No difference in symptomatic intracranial hemorrhage was observed (0/19 [0%] TNK, 1/91 [1%] alteplase p = 0.9). TNK may be associated with an increased rate of reperfusion in comparison with alteplase before EVT in BAO. Randomized controlled trials to compare TNK with alteplase in patients with BAO are warranted. NCT02388061 and NCT03340493. This study provides Class III evidence that TNK leads to higher reperfusion rates in comparison with alteplase prior to EVT in patients with BAO.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 22-03-2022
DOI: 10.1212/WNL.0000000000013302
Abstract: Detailed study of tenecteplase (TNK) in patients older than 80 years is limited. The objective of our study was to assess the safety and efficacy of TNK at 0.25 and 0.40 mg/kg doses in patients older than 80 years with large vessel occlusion. We performed a pooled analysis of the EXTEND-IA TNK randomized controlled trials (n = 502). Patients were adults presenting with ischemic stroke due to occlusion of the intracranial internal carotid, middle cerebral, or basilar artery presenting within 4.5 hours of symptom onset. We compared the treatment effect of TNK 0.25 mg/kg, TNK 0.40 mg/kg, and alteplase 0.90 mg/kg, stratifying for patient age ( years). Outcomes evaluated include 90-day modified Rankin Scale (mRS) score, all-cause mortality, and symptomatic ICH. Treatment effect was adjusted for baseline NIH Stroke Score, age, and time from symptom onset to puncture via mixed effects proportional odds and logistic regression models. In patients years (n = 137), TNK 0.25 mg/kg was associated with improved 90-day mRS (median 3 vs 4, adjusted common odds ratio (acOR) 2.70, 95% CI 1.23–5.94) and reduced mortality (acOR 0.34, 95% CI 0.13–0.91) vs 0.40 mg/kg. TNK 0.25 mg/kg was associated with improved 90-day mRS (median 3 vs 4, acOR 2.28, 95% CI 1.03–5.05) vs alteplase. No difference in 90-day mRS or mortality was detected between alteplase and TNK 0.40 mg/kg. Symptomatic ICH was observed in 4 patients treated with TNK 0.40 mg/kg, 1 patient treated with alteplase, and 0 patients treated with TNK 0.25 mg/kg. In patients ≤80 years, no differences in 90-day mRS, mortality, or symptomatic ICH were observed among TNK 0.25 mg/kg, alteplase, and TNK 0.40 mg/kg. TNK 0.25 mg/kg was associated with improved 90-day mRS and lower mortality in patients older than 80 years. No differences among the doses were observed in younger patients. NCT02388061, NCT03340493. This study provides Class II evidence that tenecteplase 0.25 mg/kg given before endovascular therapy in patients years old with large vessel occlusion stroke is associated with better functional outcomes at 90 days and reduced mortality when compared to tenecteplase 0.40 mg/kg or alteplase 0.90 mg/kg.
Location: Australia
Start Date: 2015
End Date: 2019
Funder: National Health and Medical Research Council
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