Sex Disparities in Access to Acute Stroke Care: Can Telemedicine Mitigate this Effect?

Background: Women have more frequent and severe ischemic strokes than men, and are less likely to receive treatment for acute stroke. Primary stroke centers (PSCs) have been shown to utilize treatment more frequently. Further, as telemedicine (TM) has expanded access to acute stroke care we sought to investigate the association between PSC, TM and access to acute stroke care in the state of Texas. Methods: Texas hospitals and resources were identified from the 2009 American Hospital Association Annual Survey. Hospitals were categorized as: (1) stand-alone PSCs not using telemedicine for acute stroke care, (2) PSCs using telemedicine for acute stroke care (PSC-TM), (3) non-PSC hospitals using telemedicine for acute stroke care, or (4) non-PSC hospitals not using telemedicine for acute stroke care. The proportion of the population who could reach a PSC within 60 minutes was determined for stand-alone PSCs, PSC-TM, and non-PSCs using TM for stroke care. Results: Overall, women were as likely to have 60-minute access to a PSC or PSC-TM as their male counterparts (POR 1.02, 95% CI 1.02-1.03). Women were also just as likely to have access to acute stroke care via PSC or PSC-TM or TM as men (POR 1.03, 95% CI 1.02-1.04). Discussion: Our study found no sex disparities in access to stand alone PSCs or to hospitals using TM in the state of Texas. The results of this study suggest that telemedicine can be used as part of an inclusive strategy to improve access to care equally for men and women

Enhancing the development and approval of acute stroke therapies: Stroke Therapy Academic Industry roundtable

BACKGROUND: Previous Stroke Therapy Academic Industry Roundtable (STAIR) meetings focused on preclinical evidence of drug efficacy and enhancing acute stroke trial design and performance. A fourth (STAIR-IV) was held to discuss relevant issues related to acute stroke drug development and regulatory approval. SUMMARY OF REVIEW: The STAIR-IV meeting had 3 main focus areas. The first topic was novel approaches to statistical design of acute stroke trials and appropriate outcome measures. The second focus was the need for better cooperation among participants in stroke therapy development that may be addressed through a national consortium of stroke trial centers in the United States and elsewhere. Lastly, regulatory issues related to the approval of novel mono and multiple acute stroke therapies were discussed. CONCLUSIONS: The development of additional acute stroke therapies represents a large unmet need with many remaining challenges and also opportunities to incorporate novel approaches to clinical trial design that will lead to regulatory approval. The STAIR-IV meeting explored new concepts of trial methodology and data analysis, initiatives for implementing a US clinical trialist consortium, and pertinent regulatory issues to expedite approval of novel therapies

Endovascular thrombectomy in patients with large core ischemic stroke: a cost-effectiveness analysis from the SELECT study

Background It is unknown whether endovascular thrombectomy (EVT) is cost effective in large ischemic core infarcts. Methods In the prospective, multicenter, cohort study of imaging selection study (SELECT), large core was defined as computed tomography (CT) ASPECTS(CTP) ischemic core volume (rCBF Results From 361 patients enrolled in SELECT, 105 had large core on CT or CTP (EVT 62, MM 43). 19 (31%) EVT vs 6 (14%) MM patients achieved modified Rankin Scale (mRS) score 0–2 (OR 3.27, 95% CI 1.11 to 9.62, P=0.03) with a shift towards better mRS (cOR 2.12, 95% CI 1.05 to 4.31, P=0.04). Over the projected lifetime of patients presenting with large core, EVT led to incremental costs of $33 094 and a gain of 1.34 QALYs per patient, resulting in ICER of$24 665 per QALY. EVT has a higher NMB compared with MM at lower (EVT -$42 747, MM -$76 740) and upper (EVT $155 041, MM$57 134) WTP thresholds. PSA confirmed the results and CEAC showed 77% and 92% acceptability of EVT at the WTP of $50 000 and$100 000, respectively. EVT was associated with an increment of $29 225 in societal costs. The pivotal EVT trials (HERMES, DAWN, DEFUSE 3) were dominant in a sensitivity analysis at the same inputs, with societal cost-savings of$37 901, $86 164 and$22 501 and a gain of 1.62, 2.36 and 2.21 QALYs, respectively. Conclusions In a non-randomized prospective cohort study, EVT resulted in better outcomes in large core patients with higher QALYs, NMB and high cost-effectiveness acceptability rates at current WTP thresholds. Randomized trials are needed to confirm these results. Clinical trial registration NCT0244658

No Consensus on Definition Criteria for Stroke Registry Common Data Elements

www.karger.com/cee This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License (www.karger.com/OA-license), applicable to the online version of the article only. Distribution for non-commercial purposes only

Endovascular Thrombectomy for Mild Strokes: How Low Should We Go? A Multicenter Cohort Study

Background and Purpose:Endovascular thrombectomy (EVT) is effective for acute ischemic stroke with large vessel occlusion (LVO) and NIHSS ≥6. However, EVT benefit for mild deficits LVOs (NIHSS Methods: A retrospective cohort of patients with anterior circulation LVO and NIHSSoutcome; mRS=0–2 was the secondary. Symptomatic intracerebral hemorrhage (sICH) was the safety outcome. Clinical outcomes were compared through a multivariable logistic regression after adjusting for age, presentation NIHSS, time-last-seen-normal-to-presentation, center, IV-alteplase, ASPECTS, and thrombus location. We then performed propensity score matching as a sensitivity analysis. Results were also stratified by thrombus location. Results: 214 patients (EVT-124, medical management-90) were included from 8 US and Spain centers between January/2012 and March/2017. The groups were similar in age, ASPECTS, IValteplase rate and time-last-seen-normal-to-presentation. There was no difference in mRS=0–1 between EVT and medical management (55.7% versus 54.4%, respectively, aOR=1.3, 95%CI=0.64–2.64, p=0.47). Similar results were seen for mRS=0–2 (63.3% EVT versus 67.8% medical management, aOR=0.9, 95%CI=0.43–1.88, p=0.77). In a propensity matching analysis, there was no treatment effect in 62 matched pairs (53.5%EVT, 48.4% medical management; OR=1.17, 95%CI=0.54–2.52, p=0.69). There was no statistically significant difference when stratified by any thrombus location; M1 approached significance (p=0.07). sICH rates were higher with thrombectomy (5.8% EVT versus 0% medical management, p=0.02). Conclusions: Our retrospective multicenter cohort study showed no improvement in excellent and independent functional outcomes in mild strokes (NIHS

Nitric Oxide Facilitates Delivery and Mediates Improved Outcome of Autologous Bone Marrow Mononuclear Cells in a Rodent Stroke Model

Bone marrow mononuclear cells (MNC) represent an investigational treatment for stroke. The objective of this study was to determine the relevance of vasoactive mediators, generated in response to MNC injection, as factors regulating cerebral perfusion (CP), the biodistribution of MNC, and outcome in stroke.Long Evans rats underwent transient middle cerebral artery occlusion. MNC were extracted from the bone marrow at 22 hrs and injected via the internal carotid artery or the femoral vein 2 hours later. CP was measured with MRI or continuous laser Doppler flowmetry. Serum samples were collected to measure vasoactive mediators. Animals were treated with the Nitric Oxide (NO) inhibitor, L-NAME, to establish the relevance of NO-signaling to the effect of MNC. Lesion size, MNC biodistribution, and neurological deficits were assessed.CP transiently increased in the peri-infarct region within 30 min after injecting MNC compared to saline or fibroblast control. This CP increase corresponded temporarily to serum NO elevation and was abolished by L-NAME. Pre-treatment with L-NAME reduced brain penetration of MNC and prevented MNC from reducing infarct lesion size and neurological deficits.NO generation in response to MNC may represent a mechanism underlying how MNC enter the brain, reduce lesion size, and improve outcome in ischemic stroke

Safety and efficacy of sonothrombolysis for acute ischaemic stroke: a multicentre, double-blind, phase 3, randomised controlled trial

Background: Pulsed-wave ultrasound increases the exposure of an intracranial thrombus to alteplase (recombinant tissue plasminogen activator), potentially facilitating early reperfusion. We aimed to ascertain if a novel operator-independent transcranial ultrasound device delivering low-power high-frequency ultrasound could improve functional outcome in patients treated with alteplase after acute ischaemic stroke. Methods: We did a multicentre, double-blind, phase 3, randomised controlled trial (CLOTBUST-ER) at 76 medical centres in 14 countries. We included patients with acute ischaemic stroke (National Institutes of Health Stroke Scale score ≥10) who received intravenous thrombolysis (alteplase bolus) within 3 h of symptom onset in North America and within 4·5 h of symptom onset in all other countries. Participants were randomly allocated (1:1) via an interactive web response system to either active ultrasound (2 MHz pulsed-wave ultrasound for 120 min [sonothrombolysis]; intervention group) or sham ultrasound (control group). Ultrasound was delivered using an operator-independent device, which had to be activated within 30 min of the alteplase bolus. Participants, investigators, and those assessing outcomes were unaware of group assignments. The primary outcome was improvement in the modified Rankin Scale score at 90 days in patients enrolled within 3 h of symptom onset, assessed in the intention-to-treat population as a common odds ratio (cOR) using ordinal logistic regression shift analysis. This trial is registered with ClinicalTrials.gov, number NCT01098981. The trial was stopped early by the funder after the second interim analysis because of futility. Findings: Between August, 2013, and April, 2015, 335 patients were randomly allocated to the intervention group and 341 patients to the control group. Compared with the control group, the adjusted cOR for an improvement in modified Rankin Scale score at 90 days in the intervention group was 1·05 (95% CI 0·77–1·45; p=0·74). 51 (16%) of 317 patients in the intervention group and 44 (13%) of 329 patients in the control group died (unadjusted OR 1·24, 95% CI 0·80–1·92; p=0·37) and 83 (26%) and 79 (24%), respectively, had serious adverse events (1·12, 0·79–1·60; p=0·53). Interpretation: Sonothrombolysis delivered by an operator-independent device to patients treated with alteplase after acute ischaemic stroke was feasible and most likely safe, but no clinical benefit was seen at 90 days. Sonothrombolysis could be further investigated either in randomised trials undertaken in stroke centres that are dependent on patient transfer for endovascular reperfusion therapies or in countries where these treatments cannot yet be offered as the standard of care