Thrombolysis is associated with consistent functional improvement across baseline stroke severity: a comparison of outcomes in patients from the Virtual International Stroke Trials Archive (VISTA)

<p><b>Background and Purpose:</b> Baseline stroke severity predicts outcomes among thrombolysed patients. The baseline National Institutes of Health Stroke Scale (NIHSS) thresholds are sometimes used to select patients for thrombolysis, clinical trial enrollment, or both. Using data lodged with Virtual International Stroke Trials Archive, we compared adjusted outcomes between thrombolysed and nonthrombolysed patients enrolled in neuroprotection trials (1998-2007) to assess the influence of various levels of baseline NIHSS.</p> <p><b>Method:</b> We assessed the association of treatment with outcome, measured across the modified Rankin scale score distribution, in patients categorized by baseline NIHSS in increments of 4. We used an age and baseline NIHSS adjusted Cochran-Mantel-Haenszel test followed by proportional odds logistic regression analysis. We report the Cochran-Mantel-Haenszel P values and estimated odds ratios (OR) for improved modified Rankin scale score distribution with treatment for patients within each baseline NIHSS category.</p> <p><b>Results:</b> Data were available for 5817 patients (1585 thrombolysed and 4232 nonthrombolysed). Baseline severity was greater among thrombolysed than nonthrombolysed (median baseline NIHSS, 14 vs 13; P<0.05). An association of treatment with outcome was seen independently and was of similar magnitude within each of the baseline NIHSS categories 5 to 8 (P=0.04; OR, 1.25; 95% confidence interval [CI], 1.0-1.6; N=278/934 thrombolysed/nonthrombolysed), 9 to 12 (P=0.01; OR, 1.3; 95% CI, 1.1-1.6; N=404/942), 13 to 16 (P<0.05; OR, 1.6; 95% CI, 1.3-2.1; N=342/814), 17 to 20 (P<0.05; OR, 1.7; 95% CI, 1.3-2.1; N=311/736), and 21 to 24 (P<0.05; OR, 1.6; 95% CI, 1.1-2.1; N=178/466). No association was observed within baseline NIHSS categories 1 to 4 (P=0.8; OR, 1.1; 95% CI, 0.3-4.4; N=8/161) or >= 25 (P=0.08; OR, 1.1; 95% CI, 0.7-1.9; N=64/179).</p> <p><b>Conclusions:</b> In this nonrandomized comparison, outcomes after thrombolysis were significantly better than in untreated comparators across baseline NIHSS 5 to 24. The significant association was lost only at extremes of baseline NIHSS when sample sizes were small and confidence limits were wide.</p&gt

Safety and tolerability of NXY-059 for acute intracerebral hemorrhage: the CHANT trial

<p><b>Background and Purpose:</b> NXY-059 is a free radical-trapping neuroprotectant developed for use in acute ischemic stroke. To facilitate prompt administration of treatment, potentially before neuroimaging, we investigated the safety of NXY-059 in patients with intracerebral hemorrhage (ICH).</p> <p><b>Methods:</b> We randomized 607 patients within 6 hours of acute ICH to receive 2270 mg intravenous NXY-059 over 1 hour and then up to 960 mg/h over 71 hours, or matching placebo, in addition to standard care. The primary outcome was safety: the mortality and the frequency of adverse events, and the change from baseline for a variety of serum, imaging, and electrophysiological measurements. We also studied the overall distribution of disability scores on the modified Rankin Scale (mRS) and the Barthel index.</p> <p><b>Results:</b> We treated 300 patients with NXY-059 and 303 with placebo. Treatment groups were well matched for prognostic variables including Glasgow Coma Scale, risk factors, and age. The mean National Institute of Health Stroke Scale score on admission was 14 in both groups. The baseline hemorrhage volume was 22.4±20.1 mL in the NXY-059 group and 23.3±22.8 mL in the placebo group (mean±SD). Most hemorrhages were related to hypertension or anticoagulant use. Mortality was similar in both groups: 20.3% for NXY-059 and 19.8% for placebo-treated patients. The proportion of patients who experienced an adverse event was the same for both groups, whereas for serious adverse events the proportion was slightly higher in the NXY-059 group. However, no pattern emerged to indicate a safety concern. Serum potassium fell transiently in both groups, lower in the NXY-059 group. There were no differences in 3-month function, disability, or neurological deficit scores. The odds ratio for an improved outcome in 3-month mRS scores in the NXY-059 group was 1.01 (95% CI 0.75, 1.35).</p> <p><b>Conclusions:</b> NXY-059 given within 6 hours of acute ICH has a good safety and tolerability profile, with no adverse effect on important clinical outcomes.</p&gt

NEOTROPICAL XENARTHRANS: a data set of occurrence of xenarthran species in the Neotropics

Xenarthrans – anteaters, sloths, and armadillos – have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with 24 domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, ten anteaters, and six sloths. Our dataset includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data-paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the south of the USA, Mexico, and Caribbean countries at the northern portion of the Neotropics, to its austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n=5,941), and Cyclopes sp. has the fewest (n=240). The armadillo species with the most data is Dasypus novemcinctus (n=11,588), and the least recorded for Calyptophractus retusus (n=33). With regards to sloth species, Bradypus variegatus has the most records (n=962), and Bradypus pygmaeus has the fewest (n=12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other datasets of Neotropical Series which will become available very soon (i.e. Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans dataset

Triage imaging and outcome measures for large core stroke thrombectomy - A systematic review and meta-analysis

Background Trials of endovascular thrombectomy (EVT) mostly excluded patients with large core strokes so the safety and efficacy of EVT is not well established in such patients. Moreover, the definition of large core and its measurement differ between semi-quantitative (ASPECTS) and quantitative (core volume) imaging modalities. We evaluated functional and safety outcomes in studies reporting large core stroke patients treated with EVT and compared them with patients treated with medical management (MM) only. Methods A systemic search using three large databases was performed to identify studies evaluating functional and safety outcomes in patients with large core strokes (ASPECTS<6 or core volume ≥50 cc) on CT, MRI, and Perfusion imaging according to PRISMA guidelines. A random-effect meta-analysis model was used to pool reported outcomes. Results Twelve studies reporting outcomes for patients treated with EVT compared with MM in large core strokes were included. A pooled random-effect meta-analysis of large core patients by either definition (ASPECTS <6 or ischemic core volume ≥50 cc or both) demonstrated increased functional independence (mRS-scores 0-2) rates with EVT (EVT: 122/491 (25%), MM: 45/691 (7%), pooled OR: 4.39 [95% CI: 2.53 to 7.64], overall effect Z-score: 5.25, P<0.00001, I 2 =37%, P for Cochran Q:0.15) and decreased mortality (EVT: 101/439 (23%), MM: 215/645 (33%), pooled OR:0.53 [95% CI: 0.40 to 0.71], overall effect Z-score:4.32, P<0.0001, I 2 =0%, P for Cochran Q:0.78) at 90 days, without significant increase in symptomatic intracranial hemorrhage (ICH) (EVT: 42/462 (9%), MM: 35/663 (5%), pooled OR: 1.68 [95% CI: 0.92 to 3.09], overall effect Z-score:1.68, P=0.09, I 2 =26%, P for Cochran Q:0.24). Similar effects were observed in studies reporting large core outcomes based on ASPECTS <6 and ischemic core volume ≥50 cc. We observed no heterogeneity between quantitative vs semi-quantitative large core definitions, different ischemic core thresholds, and studies reporting outcomes over different time windows in subgroup analyses. Conclusion In large core stroke patients, EVT is associated with improved functional independence and lower mortality at 90 days without significant increase in symptomatic ICH across various definitions, thresholds of large core size, and time windows. Further randomized evidence is warranted to establish EVT efficacy and safety in this population.

HeadPoST: Rightly positioned, or flat out wrong?

ObjectiveTo critique the Head Positioning in Stroke Trial (HeadPoST) study methods in relation to preceding research findings in an aim to clarify the potential efficacy of positioning interventions and direction for future research.MethodsHead positioning research prior to the conduct of HeadPoST was reviewed by a team of international stroke experts, and methods and findings were compared to HeadPoST.ResultsMethods used to select HeadPoST patients differ substantially from those used in original head positioning studies, in particular enrollment of all types of stroke. HeadPoST enrolled primarily minor strokes (median NIH Stroke Scale 4, interquartile range [IQR] 2-8) without vascular imaging confirmation of subtype; elapsed time from stroke symptom onset to the initiation of intervention was late (median 14 hours, IQR 5-35), and time from hospital admission to enrollment was delayed (median 7 hours, IQR 2-26). Intervention integrity was not reported, including ability to achieve/maintain 30° head elevation in beds lacking head elevation capabilities. Deterioration or improvement associated with the intervention is unknown as serial assessments were not completed, and the trial's 3-month outcome was powered using unrelated study data.ConclusionsThe design of HeadPoST was suboptimal to measure differences produced by the intervention. Future head positioning trials in discrete patient cohorts (in particular, large vessel occlusion) with endpoints supported by pilot work are required to understand the efficacy of this simple yet potentially important intervention. © 2018 American Academy of Neurology

Thrombolysis in stroke despite contraindications or warnings?

<p>Background and Purpose - Intravenous thrombolysis with alteplase is approved for acute ischemic stroke, but its use is limited by numerous contraindications and warnings arising from trial selection criteria or expert opinions. We examined outcomes from alteplase-treated versus untreated patients, registered in a trials archive, according to presence or absence of specified contraindications and warnings.</p> <p>Methods: We analyzed 90-day modified Rankin Scale across the whole distribution of scores using the Cochran–Mantel–Haenszel test, with adjustment for age and baseline National Institutes of Health Stroke Score, followed by proportional odds logistic regression analysis to estimate the odds ratios for preferred outcome.</p> <p>Results: We used data from 9613 ischemic stroke patients of whom 2755 were treated with thrombolysis. Adjusted odds ratios showed a broad trend of more favorable 3-month outcome associated with alteplase treatment versus no treatment in various subgroups of patients with contraindications and warnings; for example, 1.40 (95% confidence interval [CI], 1.14–1.70) in patients aged >80 (n=1805), 1.50 (95% CI, 1.03–2.18) in patients with combined history of prior stroke and diabetes mellitus (n=672), 1.42 (95% CI, 1.19–1.70) in patients on prior single antiplatelet agent (n=1626), 2.20 (95% CI, 1.12–4.32) in patients on oral anticoagulation, and International Normalized Ratio≤1.7 (n=157), 1.50 (95% CI, 1.15–1.97) in patients with baseline glucose >180 (n=879), and 1.57 (95% CI, 1.12–2.18) in patients with pretreatment National Institutes of Health Stroke Score >22 (n=620).</p> <p>Conclusions: This comprehensive retrospective analysis of various contraindications and warnings provides reassurance about benefits and risks of intravenous alteplase treatment in common clinical situations.</p&gt