K R Lees

..Glucose-potassium-insulin infusion or adjusted insulin infusions each have their proponents: both are effective but both carry a small risk of hypoglycaemia. Use of a suitable locally approved regimen seems advisable...

..NXY-059 is a free-radical-trapping agent that is neuroprotective in animal models of stroke. We tested whether it would reduce disability in humans after acute ischemic stroke...

..The Rankin scale may have advantages over the Barthel index. By combining these various approaches, acute stroke trials can be much more efficient...

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..The aim is to identify an approach that will be universally accepted and that should be included in most acute trials, without seeking to restrict options for special circumstances...

..GV150526 was generally well tolerated in patients with a clinical diagnosis of acute stroke and formal efficacy studies were considered justified...

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..This will lead to greater confidence in our ability to identify a successful treatment and to discount worthless approaches...

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..The purposes of this study were to evaluate the safety and tolerability of UK-279,276 and to examine its pharmacokinetics and pharmacodynamics (binding to neutrophil CD11b) in patients with acute stroke...

..In this review, we look at the designs and results of all controlled trials of treatments for ischaemic stroke, and try to identify opportunities to improve future treatment assessment...

..Early neurosurgery has a role limited to decompression of lesions in the posterior fossa but is under trial for large hemispheric infarcts and moderate intracerebral bleeds...

..NXY-059 is a free radical-trapping neuroprotectant demonstrated to reduce disability from ischemic stroke. We conducted analyses on additional end points and sensitivity analyses to confirm our findings...

..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...

..Early treatment may improve acute ischaemic stroke outcome. Gavestinel is a selective antagonist at the glycine site of the N-methyl-D-aspartate (NMDA) receptor, and is neuroprotective in animal models of ischaemic stroke...

..This study aimed to establish the highest safe and tolerated loading and maintenance dosing regimen of AR-R15896AR in acute ischemic stroke patients and to determine the associated plasma concentrations of AR-R15896AR...

..Confounding imbalance may also be limited by controlling or adjusting for concomitant conditions and their management. Recent trials have not yet identified a neuroprotectant, but have greatly assisted the prospects of success...

..We re-examined the effect of time to treatment with intravenous rt-PA (alteplase) on therapeutic benefit and clinical risk by adding recent trial data to the analysis...

..Population pharmacokinetic analysis estimated clearance to be 4.6 L/h. CONCLUSIONS: NXY-059 was well tolerated in patients with an acute stroke. The testing of higher doses in future trials may be justified...

..We examined whether the presence of complications 'unrelated' to index stroke at later time-points could confound outcome, and if this could be minimised through altering study end-points...

..We examined patients ≤ 80 and ≥ 81 years separately and then each age decile...

..To examine the influence of diabetes and prior stroke on outcomes, we compared data on thrombolysed patients with nonthrombolysed comparators...

..To present the preliminary experience of implementing intravenous thrombolytic therapy for acute ischaemic stroke in three UK stroke centres...

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..Previous small clinical trials in stroke patients have explored the safety and tolerability of different infusion regimens. This study was undertaken to optimize the regimen for a multicenter trial...

..The purpose of this study was to assess the safety, tolerability, and pharmacokinetics of loading and maintenance infusions of GV150526 in patients with acute stroke...

..09-0.67] and during the follow-up period (hazard ratio 0.57; 95% CI 0.35-0.93). The use of statins prior to stroke onset is associated with improved stroke survival within this cohort study with matched controls...

..To describe the United Kingdom (UK) experience with thrombolytic therapy with intravenous alteplase (rt-PA) for stroke, as captured by the Implementation of Thrombolysis in Stroke (SITS) project...

..This observation is consistent with the elevated cerebrovascular risk reported in this population, and may represent a future therapeutic target in stroke prevention...

..This study assessed the safety and tolerability of non-weight-adjusted doses of aptiganel in patients with acute ischemic stroke...

..Hyperglycaemia on presentation with acute ischaemic stroke (AIS) is associated with poor outcome, but intervention is unproven. We investigated the safety and tolerability of one method of glycaemic control...

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..It has demonstrated neuroprotective efficacy in experimental models of stroke and tolerability in healthy volunteers. We tested the safety and tolerability of ZK 200775 in patients with acute ischaemic stroke...

..Outcome following stroke is thus related more strongly to triglyceride-rich than to cholesterol-rich lipoprotein concentrations. The mechanisms explaining this require further investigation...

..Further studies to elucidate the mechanism of this observation are required...

..9; 1.2-2.9), NIHSS (2.2; 1.2-4.0) and Rankin scale (3.1; 1.6-4.9). Pneumonia and UTI are independently associated with stroke poor outcome. Patients with identified risk factors must be closely monitored for infection...

..Numerous trials of haemostatic and neuroprotective agents for intracerebral haemorrhage (ICH) have failed. We characterized the risk of complications after ICH in a trial-eligible patient population, to inform safety in future trials...

..This study confirms the association between recovery and subsequent neurological deterioration and is the first to indicate the greater importance of acute recovery at day 1 in comparison with later recovery...

..Previous clinical experience found neuropsychiatric effects attributed to sipatrigine that may have been related to peak plasma concentrations of the drug...

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..Until further trial data are available, consensus guidelines may be followed, which are generally conservative for blood glucose levels below 10 mM (180 mg/dl)...

..Induction of a hypoestrogenic state does not appear to influence cerebral vasodilatory capacity in the short term...

..To assess effect of age on response to alteplase in acute ischaemic stroke...

..The duration of treatment in recent phase 3 trials ranges from a single bolus injection to 12 weeks of oral therapy...

..Post hoc analysis indicated that this effect was seen in lacunar clinical syndromes (LACS), interaction P=0.005. We have now examined whether this interaction could be explained by confounding baseline factors...

..Previous estimates of the properties of the mRS have used diverse methodologies and may not apply to contemporary trial populations. We used a mock clinical trial design to explore inter- and intraobserver variability of the mRS...

..We sought to investigate whether allopurinol alters expression of inflammatory markers after acute ischemic stroke...

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..An ex vivo assay of 20S proteasome activity allows monitoring of the drug effect in blood. PS-519 is protective in multiple animal models of cerebral ischaemia over a range of doses that achieve 20S inhibition of 40%-80%...

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..We examined the relationship between CRP and outcome after acute ischemic stroke...

..Scoring systems exist to assist rapid identification of acute stroke but not for the more challenging diagnosis of transient ischaemic attack (TIA)...

..Certain stroke assessment scales can be derived from a review of a patient's case-record alone. We hypothesized that mRS could be successfully derived from the narrative within patient case-records...

..One promising strategy is uric acid reduction and xanthine oxidase inhibition with allopurinol. We sought to investigate whether allopurinol improves cerebrovascular reactivity (CVR) following subcortical stroke...

..Clinical trials of neuroprotective drugs have had limited success. We investigated whether selecting patients according to prognostic features would improve the statistical power of a trial to identify an efficacious treatment...

..We hypothesized that patients with low ABCD2 score predominantly have noncerebrovascular diagnoses...

..Type 2 diabetes increases risk of stroke, perhaps because of impaired cerebrovascular basal nitric oxide (NO) activity. We investigated whether this activity is improved by a 2-week course of the xanthine oxidase inhibitor allopurinol...

..We examined whether differences in index stroke severity, stroke risk factors, mortality, and stroke outcome across geographical locations remain after adjusting for case mix...

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..Video training has previously improved application of the National Institutes of Health Stroke Scale in clinical research. We developed an mRS training resource in an attempt to minimize interobserver variability...

..We examined mRS variability across a large cohort of international observers using data from a video training resource...

..Thus, while novel approaches to lysis administration are welcome, strategies to improve lay-public and medical awareness of acute stroke and potential treatments are also required...

..In the United Kingdom, area-based deprivation measures are available routinely through links with postal codes. We hypothesized that deprivation is associated with ischemic stroke risk factors, severity, subtype, and outcome...

..However, the burden of caring for stroke survivors usually rests with family members who have neither chosen nor volunteered for the role of 'carer'...

..We evaluated the degree of NIHSS improvement at 7 days (recovery) as a predictor of subsequent neurological deterioration from day 7 to day 90...

..We tested the hypotheses that baseline mean arterial BP [MAP=(2xdiastolic BP+systolic BP)/3], weighted average MAP, and an increase or decrease of >30% from baseline MAP are independently associated with stroke outcome...

..We have investigated the effect of the angiotensin-converting enzyme inhibitor perindopril on blood pressure, global and focal cerebral blood flow (CBF) and glomerular filtration rate (GFR) in a normotensive acute stroke population...

..Instead, a variable end point that takes severity or likely prognosis into account may be more informative...

..The Barthel Index (BI) and Rankin Scale (RS) have been widely used and analyzed in various ways. We sought to investigate the most powerful end point for use in acute stroke trials...

..We explored the association of admission urate level with mortality, placement, and risk of further vascular events after acute stroke...

..We aimed to compare a range of potential NIHSS end points with modified Rankin Scale (mRS) and Barthel Index (BI) end points...

..Four outcome measures of carer stress and coping at one year post-stroke were identified: carer general health, anxiety, depression and perception of stress...

..Finally, we considered the importance of the method of analysis in realizing the gain in power which may potentially be achieved by allocating treatments using stratified random blocks or adaptive stratification...

..TIA outpatient clinics may see a selective group of patients who have not had an early stroke but may be at raised risk in the medium to long term and therefore benefit from preventive treatment...

..There is greater doubt over efficacy in early prevention of proximal DVT...

..Its objectives were to investigate the haemodynamic effects of the compound, to assess its safety and tolerability in healthy male volunteers, and to provide some preliminary human pharmacokinetic data...

..The GCS verbal component may be misleading in acute stroke: a focal neurological deficit leading to dysphasia could affect the score, independently of level of consciousness...

..Trialists continue to use poorly validated approaches to outcome assessment. Given the potential effects on data quality, explicit description of methodology should be mandatory for all trials and rigour is desirable...

..Impaired CVR is associated with elevated risk of stroke. We performed a randomized, double-blind placebo-controlled trial to investigate the effect of two HRT preparations upon CVR...

..Under the aegis of the European Stroke Organisation a select committee was assembled to collate and appraise the evidence base for rehabilitation interventions...

..We hypothesized that elevated pulse pressure (PP), the difference between systolic BP (SBP) and diastolic BP (DBP), is independently associated with poor stroke outcome at 3 months...

..6% of all stroke presentations), they are most strongly predicted by the presence of other functional somatic syndromes, headache and the absence of symptoms of vertebrobasilar dysfunction...

..To examine the association between patent foramen ovale (PFO) and atrial septal aneurysm (ASA) and stroke...

..Some experimental data indicate that the binding affinity and time course of ACE inhibition can vary from one tissue to another, and among individual agents.(ABSTRACT TRUNCATED AT 250 WORDS)..

..03) after adjusting for baseline NIH stroke scale (p = 0.00001) and partial thromboplastin time ratio (p = 0.01). Relative anticoagulation does not fully explain the survival advantage in epsilon4-carrying ischemic stroke patients...

..The study aim was to assess the effects of magnesium sulfate (MgSO(4)) administration on white matter damage in vivo in spontaneously hypertensive rats...

..The Virtual International Stroke Trials Archive aims to aid the planning of clinical trials by collating and providing access to a rich resource of patient data to perform exploratory analyses...

..CONCLUSION: TCD-detectable turbulence predominantly developed at a moderate arterial stenosis and its acoustic signature with TCD is different from that caused by air bubbles and platelet-rich clots...

..We undertook a meta-analysis of relevant trials to examine whether present evidence supports delayed thrombolysis among patients selected according to mismatch criteria...

..BP-lowering is likely to be one of the most effective and generalizable strategies across a variety of major vascular events including stroke and myocardial infarction...

..The prime objective was to determine the dose that gave a clinically relevant effect in patients...

..The present article summarizes these recommendations and examines practical steps to achieve them...

..This study evaluated safety and efficacy of intravenous (IV) desmoteplase in patients with perfusion/diffusion mismatch on MRI 3 to 9 hours after onset of acute ischemic stroke...

..Both trials reported that gavestinel was ineffective in ischemic stroke. This analysis reports the results in those with primary intracerebral hemorrhage...

..Had the study not achieved a recruitment rate that far exceeded expectation, the advantages of the sequential design would have been much greater. Sequential designs appear to be an attractive option for trials in stroke...