International journal of stroke : official journal of the International Stroke Society
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The publication of the updated individual patient data meta-analysis of the larger randomised trials of intravenous rt-PA for acute ischaemic stroke has re-opened the debate about how the treatment should be used in routine practice, and what information can be expected to emerge in the next 2-3 years from the ongoing trials [the largest of which is the Third International Stroke Trial (IST-3)].
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Randomized Controlled Trial Multicenter Study
The URICO-ICTUS study, a phase 3 study of combined treatment with uric acid and rtPA administered intravenously in acute ischaemic stroke patients within the first 4.5 h of onset of symptoms.
Oxidative stress is a major contributor to brain damage in patients with ischaemic stroke. Uric acid (UA) is a potent endogenous antioxidant molecule. In experimental ischaemia in rats, the exogenous administration of uric acid is neuroprotective and enhances the effect of rtPA. Moreover, in acute stroke patients receiving rtPA within 3 h of stroke onset, the intravenous administration of uric acid is safe, prevents an early decline in uric acid levels and reduces an early increase in oxidative stress markers and in active matrix metalloproteinase nine levels. ⋯ The primary outcome measure is the proportion of patients achieving an modified Rankin Scale of 0 to 1 at 3 months after treatment or two in those patients with a prior qualifying modified Rankin Scale of 2. Secondary outcome measures include the final infarction volume measured at 72 h and the proportion of patients with symptomatic intracranial haemorrhage (> or =4 points of increase in the National Institute of Health Stroke Scale score).
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The 'penumbra' is a concept coined in animal experiments suggesting that functionally impaired tissue can survive and recover if sufficient reperfusion is re-established within a limited time period, which depends on the level of residual flow. In an ischaemic territory, irreversible damage progresses over time from the centre of the most severe flow reduction to the periphery with less disturbed perfusion. This centrifugal progression of irreversible tissue damage is characterised by a complex cascade of interconnected electrophysiological, molecular, metabolic and perfusion disturbances. ⋯ As a widely applicable clinical tool, diffusion/perfusion-weighted magnetic resonance imaging is used; the 'mismatch' between perfusion and diffusion changes serves as a surrogate marker of the penumbra. However, in comparative studies of magnetic resonance imaging and positron emission tomography, diffusion-weighted imaging showed a high false-positive rate of irreversible damage, and the perfusion-weighted-diffusion-weighted mismatch overestimated the penumbra as defined by positron emission tomography. Advanced analytical procedures of magnetic resonance imaging data may improve the reliability of these surrogate markers but should be validated with quantitative procedures.
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Disease registries assist with clinical practice improvement. The Australian Stroke Clinical Registry aims to provide national, prospective, systematic data on processes and outcomes for stroke. We describe the methods of establishment and initial experience of operation. ⋯ Australian Stroke Clinical Registry has been well established, but further refinements and broad roll-out are required before realising its potential of improving patient care through clinician feedback and allowance of local, national, and international comparative data.