Veronica Murray

Bio: Veronica Murray is an academic researcher from Karolinska Institutet. The author has contributed to research in topics: Stroke & Randomized controlled trial. The author has an hindex of 26, co-authored 47 publications receiving 4479 citations.

Thrombolysis for acute ischaemic stroke

Abstract: Background Most strokes are due to blockage of an artery in the brain by a blood clot. Prompt treatment with thrombolytic drugs can restore blood flow before major brain damage has occurred and improve recovery after stroke in some people. Thrombolytic drugs, however, can also cause serious bleeding in the brain, which can be fatal. One drug, recombinant tissue plasminogen activator (rt-PA), is licensed for use in selected patients within 4.5 hours of stroke in Europe and within three hours in the USA. There is an upper age limit of 80 years in some countries, and a limitation to mainly non-severe stroke in others. Forty per cent more data are available since this review was last updated in 2009. Objectives To determine whether, and in what circumstances, thrombolytic therapy might be an effective and safe treatment for acute ischaemic stroke. Search methods We searched the Cochrane Stroke Group Trials Register (last searched November 2013), MEDLINE (1966 to November 2013) and EMBASE (1980 to November 2013). We also handsearched conference proceedings and journals, searched reference lists and contacted pharmaceutical companies and trialists. Selection criteria Randomised trials of any thrombolytic agent compared with control in people with definite ischaemic stroke. Data collection and analysis Two review authors applied the inclusion criteria, extracted data and assessed trial quality. We verified the extracted data with investigators of all major trials, obtaining additional unpublished data if available. Main results We included 27 trials, involving 10,187 participants, testing urokinase, streptokinase, rt-PA, recombinant pro-urokinase or desmoteplase. Four trials used intra-arterial administration, while the rest used the intravenous route. Most data come from trials that started treatment up to six hours after stroke. About 44% of the trials (about 70% of the participants) were testing intravenous rt-PA. In earlier studies very few of the participants (0.5%) were aged over 80 years; in this update, 16% of participants are over 80 years of age due to the inclusion of IST-3 (53% of participants in this trial were aged over 80 years). Trials published more recently utilised computerised randomisation, so there are less likely to be baseline imbalances than in previous versions of the review. More than 50% of trials fulfilled criteria for high-grade concealment; there were few losses to follow-up for the main outcomes. Thrombolytic therapy, mostly administered up to six hours after ischaemic stroke, significantly reduced the proportion of participants who were dead or dependent (modified Rankin 3 to 6) at three to six months after stroke (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.78 to 0.93). Thrombolytic therapy increased the risk of symptomatic intracranial haemorrhage (OR 3.75, 95% CI 3.11 to 4.51), early death (OR 1.69, 95% CI 1.44 to 1.98; 13 trials, 7458 participants) and death by three to six months after stroke (OR 1.18, 95% CI 1.06 to 1.30). Early death after thrombolysis was mostly attributable to intracranial haemorrhage. Treatment within three hours of stroke was more effective in reducing death or dependency (OR 0.66, 95% CI 0.56 to 0.79) without any increase in death (OR 0.99, 95% CI 0.82 to 1.21; 11 trials, 2187 participants). There was heterogeneity between the trials. Contemporaneous antithrombotic drugs increased the risk of death. Trials testing rt-PA showed a significant reduction in death or dependency with treatment up to six hours (OR 0.84, 95% CI 0.77 to 0.93, P = 0.0006; 8 trials, 6729 participants) with significant heterogeneity; treatment within three hours was more beneficial (OR 0.65, 95% CI 0.54 to 0.80, P < 0.0001; 6 trials, 1779 participants) without heterogeneity. Participants aged over 80 years benefited equally to those aged under 80 years, particularly if treated within three hours of stroke. Authors' conclusions Thrombolytic therapy given up to six hours after stroke reduces the proportion of dead or dependent people. Those treated within the first three hours derive substantially more benefit than with later treatment. This overall benefit was apparent despite an increase in symptomatic intracranial haemorrhage, deaths at seven to 10 days, and deaths at final follow-up (except for trials testing rt-PA, which had no effect on death at final follow-up). Further trials are needed to identify the latest time window, whether people with mild stroke benefit from thrombolysis, to find ways of reducing symptomatic intracranial haemorrhage and deaths, and to identify the environment in which thrombolysis may best be given in routine practice.

Aphasia in acute stroke and relation to outcome

Abstract: . Laska AC, Hellblom A, Murray V, Kahan T, von Arbin M (Danderyd Hospital, Danderyd, Sweden). Aphasia in acute stroke and relation to outcome. J Intern Med 2001; 249: 413–422. Objectives. The natural course of aphasia in unselected, consecutive stroke patients is not well established. We investigated morbidity, mortality and recovery for different types of aphasia in consecutive unselected aphasic patients with acute stroke. Setting and subjects. In 119 aphasic patients, the type and degree of aphasia were assessed acutely and at 3, 6 and 18 months after stroke onset, using Reinvang’s ‘Grunntest for afasi’ and Amsterdam-Nijmegen-Everyday-Language-Test. Results. About one-third of patients with acute stroke had presented with aphasia. Mortality among the aphasic patients during the 18-month follow-up was twice that in non-aphasics (36 vs. 16%). Presence of atrial fibrillation was associated with poorer prognosis. At 18 months, 24% of the 119 aphasic patients had recovered completely, 43% still had significant aphasia, and 21% had died. The proportion with global aphasia decreased from almost 25% acutely to a few per cent after 18 months, that with Wernicke’s aphasia from 25% to less than 10%, whereas conduction aphasia increased from 13 to 23% during follow-up. Among those with initial mild aphasia, 70% recovered completely. Great improvement was observed in patients with initial low degree of speech function. Younger patients recovered to a greater extent than older patients. Conclusion. The high long-term mortality among aphasics may be seen as an indirect sign of advanced cardiovascular disease. A combination of different and adjusted aphasia tests provided the possibility to assess almost all acute aphasic patients. Irrespective of type and degree of aphasia, great improvements were seen in almost all aphasic patients. Even patients with severe speech impairment have a considerable potential for recovery, particularly in the first 3 months after stroke.

Thrombolysis for Acute Ischemic Stroke

Abstract: Graeme J. Hankey MD, FRACP, FRCP Section Editor: Recombinant tissue plasminogen activator (rtPA) is licensed for thrombolytic therapy in ischemic stroke if administered within 3 hours of stroke onset in selected patients (to be extended to 4.5 hours in some countries). However, many patients who could benefit from rtPA are not offered it and there is evidence that rtPA could benefit many patients who do not meet current license criteria. Furthermore, the patient characteristics that might assist in stratifying risk and benefit and the latest time at which thrombolysis may be effective remain unknown. The objectives of this study were to assess the safety and efficacy of thrombolytic agents used in acute treatment of ischemic stroke, factors that might influence risk or benefit, and estimate if current data can identify the latest time window for treatment. We used the Cochrane Stroke Group Trials Register, MEDLINE, and EMBASE; contact with trialists, and hand-searching of pertinent journals (all to October 2008). Selection criteria were randomized trials of any thrombolytic agent compared with a control in patients with definite ischemic stroke. Two reviewers applied the inclusion criteria, extracted the data (published and unpublished), and assessed trial quality. We calculated ORs and 95% CIs for all main outcomes using fixed effects methods (additionally by random effects methods where significant between-trial heterogeneity was present), calculated the effect per 1000 patients …

Guidelines for the Early Management of Patients With Acute Ischemic Stroke A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

Abstract: Background and Purpose—The authors present an overview of the current evidence and management recommendations for evaluation and treatment of adults with acute ischemic stroke. The intended audienc...

A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke

Abstract: Methods We randomly assigned eligible patients to either intraarterial treatment plus usual care or usual care alone. Eligible patients had a proximal arterial occlusion in the anterior cerebral circulation that was confirmed on vessel imaging and that could be treated intraarterially within 6 hours after symptom onset. The primary outcome was the modified Rankin scale score at 90 days; this categorical scale measures functional outcome, with scores ranging from 0 (no symptoms) to 6 (death). The treatment effect was estimated with ordinal logistic regression as a common odds ratio, adjusted for prespecified prognostic factors. The adjusted common odds ratio measured the likelihood that intraarterial treatment would lead to lower modified Rankin scores, as compared with usual care alone (shift analysis). Results We enrolled 500 patients at 16 medical centers in the Netherlands (233 assigned to intraarterial treatment and 267 to usual care alone). The mean age was 65 years (range, 23 to 96), and 445 patients (89.0%) were treated with intravenous alteplase before randomization. Retrievable stents were used in 190 of the 233 patients (81.5%) assigned to intraarterial treatment. The adjusted common odds ratio was 1.67 (95% confidence interval [CI], 1.21 to 2.30). There was an absolute difference of 13.5 percentage points (95% CI, 5.9 to 21.2) in the rate of functional independence (modified Rankin score, 0 to 2) in favor of the intervention (32.6% vs. 19.1%). There were no significant differences in mortality or the occurrence of symptomatic intracerebral hemorrhage. Conclusions In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation, intraarterial treatment administered within 6 hours after stroke onset was effective and safe. (Funded by the Dutch Heart Foundation and others; MR CLEAN Netherlands Trial Registry number, NTR1804, and Current Controlled Trials number, ISRCTN10888758.)

Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.

Abstract: Background and Purpose- The purpose of these guidelines is to provide an up-to-date comprehensive set of recommendations in a single document for clinicians caring for adult patients with acute arterial ischemic stroke. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators. These guidelines supersede the 2013 Acute Ischemic Stroke (AIS) Guidelines and are an update of the 2018 AIS Guidelines. Methods- Members of the writing group were appointed by the American Heart Association (AHA) Stroke Council's Scientific Statements Oversight Committee, representing various areas of medical expertise. Members were not allowed to participate in discussions or to vote on topics relevant to their relations with industry. An update of the 2013 AIS Guidelines was originally published in January 2018. This guideline was approved by the AHA Science Advisory and Coordinating Committee and the AHA Executive Committee. In April 2018, a revision to these guidelines, deleting some recommendations, was published online by the AHA. The writing group was asked review the original document and revise if appropriate. In June 2018, the writing group submitted a document with minor changes and with inclusion of important newly published randomized controlled trials with >100 participants and clinical outcomes at least 90 days after AIS. The document was sent to 14 peer reviewers. The writing group evaluated the peer reviewers' comments and revised when appropriate. The current final document was approved by all members of the writing group except when relationships with industry precluded members from voting and by the governing bodies of the AHA. These guidelines use the American College of Cardiology/AHA 2015 Class of Recommendations and Level of Evidence and the new AHA guidelines format. Results- These guidelines detail prehospital care, urgent and emergency evaluation and treatment with intravenous and intra-arterial therapies, and in-hospital management, including secondary prevention measures that are appropriately instituted within the first 2 weeks. The guidelines support the overarching concept of stroke systems of care in both the prehospital and hospital settings. Conclusions- These guidelines provide general recommendations based on the currently available evidence to guide clinicians caring for adult patients with acute arterial ischemic stroke. In many instances, however, only limited data exist demonstrating the urgent need for continued research on treatment of acute ischemic stroke.

SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials

Abstract: High quality protocols facilitate proper conduct, reporting, and external review of clinical trials. However, the completeness of trial protocols is often inadequate. To help improve the content and quality of protocols, an international group of stakeholders developed the SPIRIT 2013 Statement (Standard Protocol Items: Recommendations for Interventional Trials). The SPIRIT Statement provides guidance in the form of a checklist of recommended items to include in a clinical trial protocol. This SPIRIT 2013 Explanation and Elaboration paper provides important information to promote full understanding of the checklist recommendations. For each checklist item, we provide a rationale and detailed description; a model example from an actual protocol; and relevant references supporting its importance. We strongly recommend that this explanatory paper be used in conjunction with the SPIRIT Statement. A website of resources is also available (www.spirit-statement.org). The SPIRIT 2013 Explanation and Elaboration paper, together with the Statement, should help with the drafting of trial protocols. Complete documentation of key trial elements can facilitate transparency and protocol review for the benefit of all stakeholders.