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  • Ovid Technologies (Wolters Kluwer Health)  (114)
  • 1
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 42, No. 6 ( 2011-06), p. 1596-1601
    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). Methods— 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. Results— 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 〈 0.001) and cortical infarct location ( P =0.036). Infarct growth, clinical outcome, and the efficacy of t-PA were not statistically different between patterns. Conclusions— 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.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2011
    detail.hit.zdb_id: 1467823-8
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  • 2
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 43, No. suppl_1 ( 2012-02)
    Abstract: Background and purpose: The ECASS 3 study demonstrated efficacy of intravenous thrombolysis up to 4.5h after stroke onset. It has been hypothesized that some patients have tissue at risk and an acceptably low hemorrhage risk beyond 4.5h. Imaging based selection may help identify these patients for late reperfusion therapies. No randomized data have shown efficacy of tPA or reperfusion later than 4.5h after onset. We analysed the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) data to assess the effect of treatment and reperfusion on attenuation of infarct growth in the 4.5 to 6 hour time window. Methods: Patients were randomized to placebo or tissue plasminogen activator (tPA) between 4.5-6h from stroke onset (without using imaging selection criteria). Pre-treatment DWI and day 90 T2-weighted lesion volumes (average of manually outlined lesions by 2 independent raters) were compared to assess the influence of tPA and reperfusion on absolute and relative infarct growth. Day 3 volume was used when day 90 data was missing. The effect of tPA on reperfusion was also assessed. Good clinical outcome was defined as a National Institute of Health Stroke Scale (NIHSS) at day 90 0-1 or improvement ≥ 8 from baseline. Good functional outcome was defined as modified Rankin Scale (mRS) 0-2. Results: Of 69 patients treated 4.5-6hrs hours after stroke onset, infarct growth could be assessed in 63. The median relative growth was significantly lower in the tPA group compared to placebo (0.94 vs 1.68, p=0.025). There was a nonsignificant trend towards lower absolute growth (-0.17mL vs 9.56mL, p=0.069). Reperfusion markedly reduced relative (0.80 vs 1.89, p 〈 0.001) and absolute infarct growth (-2.49mL vs 39.50mL, p 〈 0.001). Reperfusion was more likely in the tPA group (57.7 vs 25.0% p=0.026) and was associated with better clinical and functional outcomes (86.4% vs 28.1% p 〈 0.001 and 72.7 vs 34.4% p=0.012). Conclusion: Thrombolysis after 4.5 hours reduced infarct growth and increased the rate of reperfusion. The strong positive effect of reperfusion on clinical and functional outcomes in this later time window is evidence of persisting salvageable ischemic penumbra. This supports continuing efforts to extend the treatment window for reperfusion therapies.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
    detail.hit.zdb_id: 1467823-8
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  • 3
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 1 ( 2021-01), p. 70-79
    Abstract: Severity-based assessment tools may assist in prehospital triage of patients to comprehensive stroke centers (CSCs) for endovascular thrombectomy (EVT), but criticisms regarding diagnostic inaccuracy have not been adequately addressed. This study aimed to quantify the benefits and disadvantages of severity-based triage in a large real-world paramedic validation of the Ambulance Clinical Triage for Acute Stroke Treatment (ACT-FAST) algorithm. Methods: Ambulance Victoria paramedics assessed the prehospital ACT-FAST algorithm in patients with suspected stroke from November 2017 to July 2019 following an 8-minute training video. All patients were transported to the nearest stroke center as per current guidelines. ACT-FAST diagnostic accuracy was compared with hospital imaging for the presence of large vessel occlusion (LVO) and need for CSC-level care (LVO, intracranial hemorrhage, and tumor). Patient-level time saving to EVT was modeled using a validated Google Maps algorithm. Disadvantages of CSC bypass examined potential thrombolysis delays in non-LVO infarcts, proportion of patients with false-negative EVT, and CSC overburdening. Results: Of 517 prehospital assessments, 168/517 (32.5%) were ACT-FAST positive and 132/517 (25.5%) had LVO. ACT-FAST sensitivity and specificity for LVO was 75.8% and 81.8%, respectively. Positive predictive value was 58.8% for LVO and 80.0% when intracranial hemorrhage and tumor (CSC-level care) were included. Within the metropolitan region, 29/55 (52.7%) of ACT-FAST-positive patients requiring EVT underwent a secondary interhospital transfer. Prehospital bypass with avoidance of secondary transfers was modeled to save 52 minutes (95% CI, 40.0–61.5) to EVT commencement. ACT-FAST was false-positive in 8 patients receiving thrombolysis (8.1% of 99 non-LVO infarcts) and false-negative in 4 patients with EVT requiring secondary transfer (5.4% of 74 EVT cases). CSC bypass was estimated to over-triage 1.1 patients-per-CSC-per-week in our region. Conclusions: The overall benefits of an ACT-FAST algorithm bypass strategy in expediting EVT and avoiding secondary transfers are estimated to substantially outweigh the disadvantages of potentially delayed thrombolysis and over-triage, with only a small proportion of EVT patients missed.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 4
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 11 ( 2022-11), p. 3295-3303
    Abstract: Although chronic kidney disease (CKD) is associated with worse stroke outcomes, data regarding the influence of CKD on intravenous thrombolysis outcomes are scarce. We sought to assess the efficacy and safety of intravenous thrombolysis for acute ischemic stroke with unknown onset time in patients with CKD. Methods: Patients with an acute stroke of unknown onset time from the EOS trials (Evaluation of Unknown Onset Stroke Thrombolysis) collaboration were evaluated using an individual patient-level database of randomized controlled trials comparing intravenous thrombolysis with placebo/standard treatment. CKD was defined as baseline estimated glomerular filtration rate of 〈 60 ml/min/1.73m 2 Mixed-effect logistic-regression analysis was performed to evaluate treatment effects. A favorable outcome was defined as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes were symptomatic intracranial hemorrhage at 22 to 36 hours and 90-day mortality. Results: Baseline data on renal function were available for 688 of 843 patients. Of these, CKD was present in 146 (21%), including 69 of 351 patients receiving alteplase and 77 of 337 patients receiving placebo/standard treatment. Overall, treatment with alteplase was associated with higher odds of favorable outcome, and CKD did not modify the treatment effect ( P interaction =0.834). A favorable outcome was observed in 31 of 69 (46%) patients with CKD in the alteplase group and in 28 of 77 (36%) patients with CKD in the control group (adjusted odds ratio, 1.19 [95% CI, 0.55–2.58] ). Among patients with CKD, symptomatic intracranial hemorrhage occurred in 2 patients (3%) in the alteplase group but in none of the controls ( P =0.133). At 90 days, death was reported in 3 patients (4%) in the alteplase group compared with 2 patients (3%) in the controls ( P =0.539). Conclusions: The present analysis indicates that the benefit of alteplase does not differ between stroke patients with unknown onset time with and without CKD, although the statistical power was lacking to confirm the efficacy in subgroups. This study only applies to mild-to-moderate or predialysis CKD.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 5
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Stroke Vol. 54, No. 7 ( 2023-07), p. 1750-1760
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 7 ( 2023-07), p. 1750-1760
    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. METHODS: 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 sample size calculation for, and ordinal analysis of, modified Rankin Scale data. RESULTS: Power formulas for Tournament Methods performed well, while the formula for ordinal logistic regression was inaccurate. Tang’s Wilcoxon-Mann-Whitney U test sample size formula exhibited the highest accuracy. All methods, including ordinal logistic regression, had almost identical empirical power for a given sample 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. CONCLUSIONS: As Tournament Method sample 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 sample size estimation. Our developed tool supports both of these recommendations ( https://www.thembc.com.au/tournamentmethods ).
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 1467823-8
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  • 6
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 43, No. 5 ( 2012-05), p. 1341-1346
    Abstract: Conflicting evidence exists as to whether focal cerebral ischemia contributes to cerebral amyloid deposition. We aimed to look at Aβ deposits, detected by N-methyl-2-(4′-methylaminophenyl)-6-hydroxybenzothiazole (PiB) positron emission tomography, in patients with recent ischemic stroke. Specifically, we hypothesized that patients with recent ischemic stroke have higher local and neocortical PiB positron emission tomography retention and that this may be associated with major vascular risk factors. Methods— Ischemic stroke patients were studied using PiB positron emission tomography within 30 days and compared to age-matched controls. Distribution volume ratio maps were created using Logan graphical analysis with the cerebellar cortex as a reference. Results— Among the 21 ischemic stroke patients (median age, 76 years; interquartile range, 68–77), the ipsilateral peri-infarct region PiB retention was higher compared to the contralateral mirror region, with a PiB distribution volume ratio difference of 0.29 (95% CI, 0.2–0.44; P =0.001) at median 10 (interquartile range, 7–14) days after stroke. Two patients also had higher PiB retention within the infarct compared to the contralateral side. There was no difference in the neocortical PiB retention elsewhere in the brain among ischemic stroke patients compared with 22 age-matched normal controls ( P =0.22). Among the risk factors in the ischemic stroke patients, diabetes was associated with a higher neocortical PiB retention (Spearman Rho=0.48; 95% CI, 0.28–0.72). Conclusions— PiB retention was higher in the peri-infarct region among patients with recent ischemic stroke. This did not translate into a higher global neocortical PiB retention except possibly in patients with diabetes. The cause of the focal PiB retention is uncertain and requires further investigation.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
    detail.hit.zdb_id: 1467823-8
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  • 7
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 44, No. 1 ( 2013-01), p. 87-93
    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 individual 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. Methods— The EPITHET–DEFUSE study datasets were pooled while retaining the original inclusion and exclusion criteria. Significant hypoperfusion was defined as a Tmax delay 〉 6 seconds), and coregistration techniques were used to define MR diffusion-weighted imaging/perfusion-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. Results— 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. Conclusions— 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. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00238537
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
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  • 8
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Stroke Vol. 47, No. 10 ( 2016-10), p. 2638-2640
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 47, No. 10 ( 2016-10), p. 2638-2640
    Abstract: Taking appropriate action in the prehospital setting is important for rapid stroke diagnosis in adults. Data are lacking for children. We aimed to describe parental care–seeking behavior and prehospital timelines of care in childhood arterial ischemic stroke. Methods— A structured questionnaire was developed, using value-focused event-driven conceptual modeling techniques, to interview parents of children presenting to the emergency department with arterial ischemic stroke from 2008 to 2014. Results— Twenty-five parents (median age 41 years, interquartile range 36–45) were interviewed. Twenty-four children were awake, and 1 child was asleep at stroke onset; 23 had sudden onset symptoms. Location at stroke onset included home (72%), school (8%), or other setting (20%). Carergivers present included parent (76%), another child (8%), teacher (4%), or alone (8%). Eighty-four percent of parents thought symptoms were serious, and 83% thought immediate action was required, but only 48% considered the possibility of stroke. Initial actions included calling an ambulance (36%), wait and see (24%), calling a general practitioner (16%) or family member (8%), and driving to the emergency department or family physician (both 8%). Median time from onset to emergency department arrival was 76 minutes (interquartile range 53–187), being shorter for ambulance-transported patients. Conclusions— Stroke recognition and care-seeking behavior are suboptimal, with less than half the parents considering stroke or calling an ambulance. Initiatives are required to educate parents about appropriate actions to facilitate time-critical interventions.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
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  • 9
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 1 ( 2021-01), p. 339-343
    Abstract: Lacunar syndromes correlate with a lacunar stroke on imaging in 50% to 60% of cases. Computed tomography perfusion (CTP) is becoming the preferred imaging modality for acute stroke triage. We aimed to estimate the sensitivity, specificity, and predictive values for noncontrast computed tomography and CTP in lacunar syndromes, and for cortical, subcortical, and posterior fossa regions. Methods: A retrospective analysis of confirmed ischemic stroke patients who underwent acute CTP and follow-up magnetic resonance imaging between 2010 and 2018 was performed. Brain noncontrast computed tomography and CTP were assessed independently by 2 stroke neurologists. Receiver operating characteristic curve analysis was performed to estimate sensitivity, specificity, and area under the curve (AUC) for the detection of strokes in patients with lacunar syndromes using different CTP maps. Results: We found 106 clinical lacunar syndromes, but on diffusion-weighted imaging, these consisted of 59 lacunar, 33 cortical, and 14 posterior fossa strokes. The discrimination of ischemia identification was very poor using noncontrast computed tomography in all 3 regions, but good for cortical (AUC, 0.82) and poor for subcortical and posterior regions (AUCs, 0.55 and 0.66) using automated core-penumbra maps. The addition of delay time and mean transient time maps substantially increased subcortical (AUC, 0.80) and slightly posterior stroke detection (AUC, 0.69). Conclusions: Analysis of mean transient time and delay time maps in combination with core-penumbra maps improves detection of subcortical and posterior strokes.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 10
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 3 ( 2023-03), p. 706-714
    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). Methods: 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 〉 50% 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. Results: 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). Conclusions: 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.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 1467823-8
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