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  • Ovid Technologies (Wolters Kluwer Health)  (41)
  • Sprigg, Nikola  (41)
  • Medicine  (41)
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  • Ovid Technologies (Wolters Kluwer Health)  (41)
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  • Medicine  (41)
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  • 1
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 46, No. 11 ( 2015-11), p. 3194-3201
    Abstract: Nitric oxide donors are candidate treatments for acute stroke, potentially through hemodynamic, reperfusion, and neuroprotectant effects, especially if given early. Although the large Efficacy of Nitric Oxide in Stroke (ENOS) trial of transdermal glyceryl trinitrate (GTN) was neutral, a prespecified subgroup suggested that GTN improved functional outcome if administered early after stroke onset. Methods— Prospective analysis of subgroup of patients randomized into the ENOS trial within 6 hours of stroke onset. Safety and efficacy of GTN versus no GTN were assessed using data on early and late outcomes. Results— Two hundred seventy-three patients were randomized within 6 hours of ictus: mean (SD) age, 69.9 (12.7) years; men, 154 (56.4%); ischemic stroke, 208 (76.2%); Scandinavian Stroke Scale, 32.1 (11.9); and total anterior circulation syndrome, 86 (31.5%). When compared with no GTN, the first dose of GTN lowered blood pressure by 9.4/3.3 mm Hg ( P 〈 0.01, P =0.064) and shifted the modified Rankin Scale to a better outcome by day 90, adjusted common odds ratio, 0.51 (95% confidence interval, 0.32–0.80). Significant beneficial effects were also seen with GTN for disability (Barthel Index), quality of life (EuroQol-Visual Analogue Scale), cognition (telephone Mini-Mental State Examination), and mood (Zung Depression Scale). GTN was safe to administer with less serious adverse events by day 90 (GTN 18.8% versus no GTN 34.1%) and death (hazard ratio, 0.44; 95% confidence interval, 0.20–0.99; P =0.047). Conclusions— In a subgroup analysis of the large ENOS trial, transdermal GTN was safe to administer and associated with improved functional outcome and fewer deaths when administered within 6 hours of stroke onset. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00989716.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 1467823-8
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  • 2
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 51, No. 1 ( 2020-01), p. 209-215
    Abstract: Relative signal intensity of acute ischemic stroke lesions in fluid-attenuated inversion recovery (fluid-attenuated inversion recovery relative signal intensity [FLAIR-rSI]) magnetic resonance imaging is associated with time elapsed since stroke onset with higher intensities signifying longer time intervals. In the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke Trial), intravenous alteplase was effective in patients with unknown onset stroke selected by visual assessment of diffusion weighted imaging fluid-attenuated inversion recovery mismatch, that is, in those with no marked fluid-attenuated inversion recovery hyperintensity in the region of the acute diffusion weighted imaging lesion. In this post hoc analysis, we investigated whether quantitatively measured FLAIR-rSI modifies treatment effect of intravenous alteplase. Methods— FLAIR-rSI of stroke lesions was measured relative to signal intensity in a mirrored region in the contralesional hemisphere. The relationship between FLAIR-rSI and treatment effect on functional outcome assessed by the modified Rankin Scale (mRS) after 90 days was analyzed by binary logistic regression using different end points, that is, favorable outcome defined as mRS score of 0 to 1, independent outcome defined as mRS score of 0 to 2, ordinal analysis of mRS scores (shift analysis). All models were adjusted for National Institutes of Health Stroke Scale at symptom onset and stroke lesion volume. Results— FLAIR-rSI was successfully quantified in stroke lesions in 433 patients (86% of 503 patients included in WAKE-UP). Mean FLAIR-rSI was 1.06 (SD, 0.09). Interaction of FLAIR-rSI and treatment effect was not significant for mRS score of 0 to 1 ( P =0.169) and shift analysis ( P =0.086) but reached significance for mRS score of 0 to 2 ( P =0.004). We observed a smooth continuing trend of decreasing treatment effects in relation to clinical end points with increasing FLAIR-rSI. Conclusions— In patients in whom no marked parenchymal fluid-attenuated inversion recovery hyperintensity was detected by visual judgement in the WAKE-UP trial, higher FLAIR-rSI of diffusion weighted imaging lesions was associated with decreased treatment effects of intravenous thrombolysis. This parallels the known association of treatment effect and elapsing time of stroke onset.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1467823-8
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  • 3
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 48, No. 5 ( 2017-05), p. 1412-1415
    Abstract: Repeated episodes of limb ischemia and reperfusion (remote ischemic conditioning [RIC]) may improve outcome after acute stroke. Methods— We performed a pilot blinded placebo-controlled trial in patients with acute ischemic stroke, randomized 1:1 to receive 4 cycles of RIC within 24 hours of ictus. The primary outcome was tolerability and feasibility. Secondary outcomes included safety, clinical efficacy (day 90), putative biomarkers (pre- and post-intervention, day 4), and exploratory hemodynamic measures. Results— Twenty-six patients (13 RIC and 13 sham) were recruited 15.8 hours (SD 6.2) post-onset, age 76.2 years (SD 10.5), blood pressure 159/83 mm Hg (SD 25/11), and National Institutes of Health Stroke Scale (NIHSS) score 5 (interquartile range, 3.75–9.25). RIC was well tolerated with 49 out of 52 cycles completed in full. Three patients experienced vascular events in the sham group: 2 ischemic strokes and 2 myocardial infarcts versus none in the RIC group ( P =0.076, log-rank test). Compared with sham, there was a significant decrease in day 90 NIHSS score in the RIC group, median NIHSS score 1 (interquartile range, 0.5–5) versus 3 (interquartile range, 2–9.5; P =0.04); RIC augmented plasma HSP27 (heat shock protein 27; P 〈 0.05, repeated 2-way ANOVA) and phosphorylated HSP27 ( P 〈 0.001) but not plasma S100-β, matrix metalloproteinase-9, endocannabinoids, or arterial compliance. Conclusions— RIC after acute stroke is well tolerated and appears safe and feasible. RIC may improve neurological outcome, and protective mechanisms may be mediated through HSP27. A larger trial is warranted. Clinical Trial Registration— URL: http://www.isrctn.com . Unique identifier: ISRCTN86672015.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
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  • 4
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 5 ( 2021-05), p. 1905-1914
    Abstract: This invited special report is based on an award presentation at the World Stroke Organization/European Stroke Organization Conference in November of 2020 outlining progress in the acute management of intracerebral hemorrhage (ICH) over the past 35 years. ICH is the second most common and the deadliest type of stroke for which there is no scientifically proven medical or surgical treatment. Prospective studies from the 1990s onward have demonstrated that most growth of spontaneous ICH occurs within the first 2 to 3 hours and that growth of ICH and resulting volumes of ICH and intraventricular hemorrhage are modifiable factors that can improve outcome. Trials focusing on early treatment of elevated blood pressure have suggested a target systolic blood pressure of 140 mm Hg, but none of the trials were positive by their primary end point. Hemostatic agents to decrease bleeding in spontaneous ICH have included desmopressin, tranexamic acid, and rFVIIa (recombinant factor VIIa) without clear benefit, and platelet infusions which were associated with harm. Hemostatic agents delivered within the first several hours have the greatest impact on growth of ICH and potentially on outcome. No large Phase III surgical ICH trial has been positive by primary end point, but pooled analyses suggest that earlier ICH removal is more likely to be beneficial. Recent trials emphasize maximization of clot removal and minimizing brain injury from the surgical approach. The future of ICH therapy must focus on delivery of medical and surgical therapies as soon as possible if we are to improve outcomes.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1467823-8
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  • 5
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Stroke Vol. 49, No. 7 ( 2018-07), p. 1784-1790
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 49, No. 7 ( 2018-07), p. 1784-1790
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 1467823-8
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  • 6
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 9 ( 2023-09), p. 2223-2234
    Abstract: Evidence-based hemostatic treatment for intracerebral hemorrhage (ICH) associated with non–vitamin K antagonist oral anticoagulants (NOACs) is lacking. Tranexamic acid (TXA) is an antifibrinolytic drug potentially limiting hematoma expansion. We aimed to assess the efficacy and safety of TXA in NOAC-ICH. METHODS: We performed a double-blind, randomized, placebo-controlled trial at 6 Swiss stroke centers. Patients with NOAC-ICH within 12 hours of symptom onset and 48 hours of last NOAC intake were randomized (1:1) to receive either intravenous TXA (1 g over 10 minutes followed by 1 g over 8 hours) or matching placebo in addition to standard medical care via a centralized Web-based procedure with minimization on key prognostic factors. All participants and investigators were masked to treatment allocation. Primary outcome was hematoma expansion, defined as ≥33% relative or ≥6 mL absolute volume increase at 24 hours and analyzed using logistic regression adjusted for baseline hematoma volume on an intention-to-treat basis. RESULTS: Between December 12, 2016, and September 30, 2021, we randomized 63 patients (median age, 82 years [interquartile range, 76–86]; 40% women; median hematoma volume, 11.5 [4.8–27.4] mL) of the 109 intended sample size before premature trial discontinuation due to exhausted funding. The primary outcome did not differ between TXA (n=32) and placebo (n=31) arms (12 [38%] versus 14 [45%] ; adjusted odds ratio, 0.63 [95% CI, 0.22–1.82]; P =0.40). There was a signal for interaction with onset-to-treatment time ( P interaction =0.024), favoring TXA when administered within 6 hours of symptom onset. Between the TXA and placebo arms, the proportion of participants who died (15 [47%] versus 13 [42%] ; adjusted odds ratio, 1.07 [0.37–3.04]; P =0.91) or had major thromboembolic complications within 90 days (4 [13%] versus 2 [6%] ; odds ratio, 1.86 [0.37–9.50]; P =0.45) did not differ. All thromboembolic events occurred at least 2 weeks after study treatment, exclusively in participants not restarted on oral anticoagulation. CONCLUSIONS: In a smaller-than-intended NOAC-ICH patient sample, we found no evidence that TXA prevents hematoma expansion, but there were no major safety concerns. Larger trials on hemostatic treatments targeting an early treatment window are needed for NOAC-ICH. REGISTRATION: URL: https://clinicaltrials.gov ; Unique identifier: NCT02866838.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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  • 7
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 51, No. 4 ( 2020-04), p. 1333-1338
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1467823-8
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  • 8
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2013
    In:  Stroke Vol. 44, No. 12 ( 2013-12), p. 3458-3462
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 44, No. 12 ( 2013-12), p. 3458-3462
    Abstract: Health-related quality of life, a key outcome after stroke, plays a role in the analysis of treatment cost-effectiveness. Some measures of health-related quality of life allow for a quality of life worse than death; the characteristics of such patients have not been well described. Methods— Data from the Efficacy of Nitric Oxide in Stroke (ENOS) trial were used to explore health-related quality of life after stroke. The EuroQol questionnaire (EQ-5D) was performed at day 90, and a health utility score (HUS) was calculated. HUS was defined as follows: poor-good HUS 〉 0, death HUS=0, and very poor HUS 〈 0. The characteristics and outcomes of patients with HUS 〈 0 were then explored. Results— Of the 2569 patients, 303 (11.8%) died, and of the 2238 with quality of life data available, of whom 724 (32.3%) were completed by a proxy, 1959 (87.5%) had an HUS 〉 0 and 279 (12.5%) had an HUS 〈 0. Patients with HUS 〈 0 were more likely to be older, women, have severe stroke, have proxy responders, and be institutionalized. Dominant hemisphere strokes were more likely to have proxy responders but not HUS 〈 0. HUS was strongly correlated with dependency (modified Rankin Scale, r =−0.78) and disability (Barthel index, r =0.84) and moderately correlated with mood (Zung depression score, r =−0.59) and baseline severity ( r =0.51). All but 1 patient with modified Rankin Scale of 5 had an HUS 〈 0. Conclusions— Very low health-related quality of life is relatively common after stroke, particularly in patients with mobility problems or who are dependent on help for usual activities, and is related to poor functional outcome measures. Clinical Trial Registration— URL: http://www.controlled-trials.com/ . Unique identifier: ISRCTN99414122.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 1467823-8
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  • 9
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 51, No. 1 ( 2020-01), p. 121-128
    Abstract: Blend, black hole, island signs, and hypodensities are reported to predict hematoma expansion in acute intracerebral hemorrhage. We explored the value of these noncontrast computed tomography signs in predicting hematoma expansion and functional outcome in our cohort of intracerebral hemorrhage. Methods— The TICH-2 (Tranexamic acid for IntraCerebral Hemorrhage-2) was a prospective randomized controlled trial exploring the efficacy and safety of tranexamic acid in acute intracerebral hemorrhage. Baseline and 24-hour computed tomography scans of trial participants were analyzed. Hematoma expansion was defined as an increase in hematoma volume of 〉 33% or 〉 6 mL on 24-hour computed tomography. Poor functional outcome was defined as modified Rankin Scale of 4 to 6 at day 90. Multivariable logistic regression was performed to identify predictors of hematoma expansion and poor functional outcome. Results— Of 2325 patients recruited, 2077 (89.3%) had valid baseline and 24-hour scans. Five hundred seventy patients (27.4%) had hematoma expansion while 1259 patients (54.6%) had poor functional outcome. The prevalence of noncontrast computed tomography signs was blend sign, 366 (16.1%); black hole sign, 414 (18.2%); island sign, 200 (8.8%); and hypodensities, 701 (30.2%). Blend sign (adjusted odds ratio [aOR] 1.53 [95% CI, 1.16–2.03] ; P =0.003), black hole (aOR, 2.03 [1.34–3.08]; P =0.001), and hypodensities (aOR, 2.06 [1.48–2.89]; P 〈 0.001) were independent predictors of hematoma expansion on multivariable analysis with adjustment for covariates. Black hole sign (aOR, 1.52 [1.10–2.11]; P =0.012), hypodensities (aOR, 1.37 [1.05–1.78]; P =0.019), and island sign (aOR, 2.59 [1.21–5.55]; P =0.014) were significant predictors of poor functional outcome. Tranexamic acid reduced the risk of hematoma expansion (aOR, 0.77 [0.63–0.94]; P =0.010), but there was no significant interaction between the presence of noncontrast computed tomography signs and benefit of tranexamic acid on hematoma expansion and functional outcome ( P interaction all 〉 0.05). Conclusions— Blend sign, black hole sign, and hypodensities predict hematoma expansion while black hole sign, hypodensities, and island signs predict poor functional outcome. Noncontrast computed tomography signs did not predict a better response to tranexamic acid. Clinical Trial Registration— URL: https://www.isrctn.com . Unique identifier: ISRCTN93732214.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1467823-8
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  • 10
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 37, No. 12 ( 2006-12), p. 2979-2983
    Abstract: Background and Purpose— Loss of motor function is common after stroke and leads to significant chronic disability. Stem cells are capable of self-renewal and of differentiating into multiple cell types, including neurones, glia, and vascular cells. We assessed the safety of granulocyte-colony–stimulating factor (G-CSF) after stroke and its effect on circulating CD34+ stem cells. Methods— We performed a 2-center, dose-escalation, double-blind, randomized, placebo-controlled pilot trial (ISRCTN 16784092) of G-CSF (6 blocks of 1 to 10 μg/kg SC, 1 or 5 daily doses) in 36 patients with recent ischemic stroke. Circulating CD34+ stem cells were measured by flow cytometry; blood counts and measures of safety and functional outcome were also monitored. All measures were made blinded to treatment. Results— Thirty-six patients, whose mean±SD age was 76±8 years and of whom 50% were male, were recruited. G-CSF (5 days of 10 μg/kg) increased CD34+ count in a dose-dependent manner, from 2.5 to 37.7 at day 5 (area under curve, P =0.005). A dose-dependent rise in white cell count ( P 〈 0.001) was also seen. There was no difference between treatment groups in the number of patients with serious adverse events: G-CSF, 7/24 (29%) versus placebo 3/12 (25%), or in their dependence (modified Rankin Scale, median 4, interquartile range, 3 to 5) at 90 days. Conclusions— G-CSF is effective at mobilizing bone marrow CD34+ stem cells in patients with recent ischemic stroke. Administration is feasible and appears to be safe and well tolerated. The fate of mobilized cells and their effect on functional outcome remain to be determined.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2006
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