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Biomedical subjects

Keith W Muir

Publications and source records attributed to Keith W Muir.

15 recordsLinked to original sources
PubMed2006

Insular cortex hypoperfusion and acute phase blood glucose after stroke: a CT perfusion study.

BACKGROUND AND PURPOSE: Insular cortex ischemia is proposed to mediate a sympathetic stimulus that leads to acute hyperglycemia after stroke. METHODS: We retrospectively analyzed insular perfusion on perfusion CT (median 180 minutes after onset) in 35 patients. RESULTS: We found no association of hypoperfusion (relative cerebral blood flow <0.51) with early (<6 hours) or delayed (<72 hours) hyperglycemia, or hemispheric lateralization. CONCLUSIONS: Insular cortex hypoperfusion <6 hours after stroke onset was not associated with hyperglycemia.

Aged↗
PubMed2006

Effect of smoking status on outcome after acute ischemic stroke.

BACKGROUND: The status of smoking as a risk factor for the occurrence of stroke is well established. However, there is a paucity of data on the relationship between smoking status and acute stroke outcomes. We evaluated the role of recent smoking as a prognostic factor following acute ischemic stroke. METHODS: We analyzed data from patients enrolled in the Intravenous Magnesium Efficacy in Stroke (IMAGES) trial. Outcome measures studied included change in IMAGES stroke score, poor functional outcomes at day 30 and 90 (defined as Rankin Scale >1 and Barthel Index <95), and survival over the first 3 months after stroke. The independent effect of smoking status (subjects who had smoked in the past year) on outcome was evaluated by logistic regression analysis and Cox's proportional hazards model, adjusting for variables known to predict outcome after ischemic stroke. RESULTS: There were 2,386 subjects in the IMAGES efficacy dataset, including 615 recent or current smokers and 1,771 nonsmokers, among whom smokers were younger (p < 0.0001). After adjusting for covariates, smokers had increased odds of poor 90-day functional outcome independently of other statistically significant predictor variables, as assessed by Rankin Scale (odds ratio 1.38; 95% confidence interval 1.09-1.75) and Barthel Index (odds ratio 1.42; 95% confidence interval 1.13-1.79) at day 90. Smoking status did not affect survival at day 90. CONCLUSIONS: Current or recent smokers experience poorer functional outcomes than nonsmokers 3 months after acute ischemic stroke.

Aged↗
PubMed2006

Imaging of acute stroke.

Thrombolytic therapy has led to a higher proportion of patients presenting to hospital early, and this, with parallel developments in imaging technology, has greatly improved the understanding of acute stroke pathophysiology. Additionally, MRI, including diffusion-weighted imaging (DWI) and gradient echo, or T2*, imaging is important in understanding basic structural information--such as distinguishing acute ischaemia from haemorrhage. It has also greatly increased sensitivity in the diagnosis of acute cerebral ischaemia. The pathophysiology of the ischaemic penumbra can now be assessed with CT or MRI-based perfusion imaging techniques, which are widely available and clinically applicable. Pathophysiological information from CT or MRI increasingly helps clinical trial design, may allow targeted therapy in individual patients, and may extend the time scale for reperfusion therapy.

Animals↗
PubMed2005

Glutamate-based therapeutic approaches: clinical trials with NMDA antagonists.

The majority of clinical trials of N-methyl d-aspartate antagonists have been conducted in the fields of stroke, traumatic brain injury (TBI) and dementia. Stroke and TBI trials have involved more than 9000 patients, but have yielded no therapeutically useful agents, with the possible exception of magnesium for treatment of subarachnoid haemorrhage. Several of the synthetic N-methyl D-aspartate antagonist development programmes have been abandoned owing to concerns about drug toxicity, particularly in stroke. Systematic reviews in stroke and TBI have shown that definitive conclusions cannot be drawn for most agents owing to early termination of trials. In dementia, memantine has shown some benefit in moderate-to-severe Alzheimer's disease, with no clear benefit to date for milder stages of Alzheimer's disease or for vascular dementia. Other therapeutic areas of promise remain inadequately explored at present.

Brain Injuries↗
PubMed2005

Evaluation of C-reactive protein measurement for assessing the risk and prognosis in ischemic stroke: a statement for health care professionals from the CRP Pooling Project members.

BACKGROUND AND PURPOSE: Several studies have shown, in different populations, that modest elevation of plasma C-reactive protein (CRP) in the range seen in apparently healthy individuals is a strong predictor of future vascular events. Elevated plasma CRP concentrations are also associated with an increased risk of cerebrovascular events and an increased risk of fatal and nonfatal cardiovascular events in ischemic stroke patients. These epidemiological and clinical observations suggest that determination of plasma CRP concentrations could be used as an adjunct for risk assessment in primary and secondary prevention of cerebrovascular disease and be of prognostic value. The aim of this review is to summarize the evidence for CRP as an independent predictor of cerebrovascular events in at-risk individuals and ischemic stroke patients and to consider its usefulness in evaluating prognosis after stroke. SUMMARY OF REVIEW: CRP fulfils most of the requirements of a new risk and prognostic predictor, but several issues await further confirmation and clarification before this marker can be included in the routine evaluation of stroke patients and subjects at risk for cerebrovascular disease. Potentially important associations have been established between elevated plasma CRP concentrations and increased efficacy of established therapies, particularly lipid-lowering therapy with statins. CONCLUSIONS: At present, there is not sufficient evidence to recommend measurement of CRP in the routine evaluation of cerebrovascular disease risk in primary prevention, because there is insufficient evidence as to whether early detection, or intervention based on detection, improves health outcomes, although shared risk of cardiovascular disease indicates this may be of value. In secondary prevention of stroke, elevated CRP adds to existing prognostic markers, but it remains to be established whether specific therapeutic options can be derived from this.

Aged↗
PubMed2005

Reliability of the modified Rankin Scale across multiple raters: benefits of a structured interview.

BACKGROUND AND PURPOSE: The modified Rankin Scale (mRS) is widely used to assess global outcome after stroke. The aim of the study was to examine rater variability in assessing functional outcomes using the conventional mRS, and to investigate whether use of a structured interview (mRS-SI) reduced this variability. METHODS: Inter-rater agreement was studied among raters from 3 stroke centers. Fifteen raters were recruited who were experienced in stroke care but came from a variety of professional backgrounds. Patients at least 6 months after stroke were first assessed using conventional mRS definitions. After completion of initial mRS assessments, raters underwent training in the use of a structured interview, and patients were re-assessed. In a separate component of the study, intrarater variability was studied using 2 raters who performed repeat assessments using the mRS and the mRS-SI. The design of the latter part of the study also allowed investigation of possible improvement in rater agreement caused by repetition of the assessments. Agreement was measured using the kappa statistic (unweighted and weighted using quadratic weights). RESULTS: Inter-rater reliability: Pairs of raters assessed a total of 113 patients on the mRS and mRS-SI. For the mRS, overall agreement between raters was 43% (kappa=0.25, kappa(w)=0.71), and for the structured interview overall agreement was 81% (kappa=0.74, kappa(w)=0.91). Agreement between raters was significantly greater on the mRS-SI than the mRS (P<0.001). Intrarater reliability: Repeatability of both the mRS and mRS-SI was excellent (kappa=0.81, kappa(w) > or =0.94). CONCLUSIONS: Although individual raters are consistent in their use of the mRS, inter-rater variability is nonetheless substantial. Rater variability on the mRS is thus particularly problematic for studies involving multiple raters. There was no evidence that improvement in inter-rater agreement occurred simply with repetition of the assessment. Use of a structured interview improves agreement between raters in the assessment of global outcome after stroke.

Adult↗
PubMed2004

Basilar artery occlusion.

Basilar artery occlusion is assumed to carry a grave prognosis, with mortality rates of up to 90%. Diagnosis is often delayed, or even missed, as a result of the variety of clinical presentations seen with this condition. The pathogenesis of occlusion can be secondary to both local atherothrombosis or cardioembolism. The use of noninvasive imaging such as magnetic resonance imaging and computed tomography angiography has improved recognition of clinical syndromes associated with occlusion. Although no randomized studies have been performed, recanalization of the vascular occlusion, particularly with thrombolytic agents, appears to result in improved outcomes in selected patients. However, the optimum timing for therapy is unclear, and reperfusion therapy may need to be combined with definitive vascular treatment of underlying vascular stenosis. Increasing awareness of this condition may reveal the natural history to be more diverse than previously recognized.

Arterial Occlusive Diseases↗
PubMed2002

Heterogeneity of stroke pathophysiology and neuroprotective clinical trial design.

BACKGROUND AND PURPOSE: Tissue substrates for action of neuroprotective agents may be absent in a significant proportion of strokes. Pathophysiological heterogeneity is a possible contributor to negative neuroprotective trials. METHODS: Stroke subtypes and their individual outcomes in neuroprotective trial control populations were used to derive models incorporating accuracy of clinical classification and probability of an ischemic penumbra. With the use of treatment effect sizes from successful trials (predominantly of reperfusion therapies), sample sizes for neuroprotective trials were calculated. The potential influence of altered recruitment strategies was explored. RESULTS: The proportion of informative patients in 2 large neuroprotective trials was probably only 27% to 30%. Optimistically, this proportion may be 50%; pessimistically, it may be only 17%. These figures necessitate a sample size of 3700 to 4500 subjects per group; at best, 1800 to 2200 are needed per group with optimistic assumptions about treatment effect. Strategies to enhance the proportion with tissue substrate for neuroprotection could reduce sample size to 500 per group and simultaneously reduce the total number of patients screened compared with inclusive trials. CONCLUSIONS: Population heterogeneity alone may be sufficient to explain negative neuroprotective trials because even in the largest trials to date sample size is inadequate to detect effect size equivalent to those with thrombolysis, and it is possible that they have been severely underpowered. Reliable trials with inclusive entry criteria may be too large to be commercially feasible for novel compounds. Both sample size and total number of patients needing to be screened should be reduced by restricting entry to patients more likely to have a tissue target.

Clinical Trials as Topic↗
PubMed2002

Improving the assessment of outcomes in stroke: use of a structured interview to assign grades on the modified Rankin Scale.

BACKGROUND AND PURPOSE: The modified Rankin Scale is widely used to assess changes in activity and lifestyle after stroke, but it has been criticized for its subjectivity. The purpose of the present study was to compare conventional assessment on the modified Rankin Scale with assessment through a structured interview. METHODS: Sixty-three patients with stroke 6 to 24 months previously were interviewed and graded independently on the modified Rankin Scale by 2 observers. These observers then underwent training in use of a structured interview for the scale that covered 5 areas of everyday function. Eight weeks after the first assessment, the same observers reassessed 58 of these patients using the structured interview. RESULTS: Interrater reliability was measured with the kappa statistic (weighted with quadratic weights). For the scale applied conventionally, overall agreement between the 2 raters was 57% (kappa(w)=0.78); 1 rater assigned significantly lower grades than the other (P=0.048). On the structured interview, the overall agreement between raters was 78% (kappa(w)=0.93), and there was no overall difference between raters in grades assigned (P=0.17). Rankin grades from the conventional assessment and the structured interview were highly correlated, but there was significantly less disagreement between raters when the structured interview was used (P=0.004). CONCLUSIONS: Variability and bias between raters in assigning patients to Rankin grades may be reduced by use of a structured interview. Use of a structured interview for the scale could potentially improve the quality of results from clinical studies in stroke.

Activities of Daily Living↗