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Biomedical subjects

Stephen M Davis

Publications and source records attributed to Stephen M Davis.

At least 19 recordsLinked to original sources
PubMed2005

When to measure lipid profile after stroke?

BACKGROUND: Although acute decreases in total cholesterol (TC) are well documented in myocardial infarction, previous stroke studies have produced conflicting results. The timing of lipid estimation in ischemic stroke is becoming important with recent trial results indicating the benefits of statins. We therefore aimed to determine the optimal time for lipid measurements after stroke. We hypothesized that TC would acutely decrease after stroke and return to baseline by 12 weeks. METHODS AND RESULTS: We performed a prospective, observational study of 50 patients (age 68.5 +/- 11.2 years) who presented with acute ischemic stroke. Of these, 22 (44%) were HMG-CoA reductase (statin) naïve, 15 (30%) had already been on statins and 13 (26%) were commenced on statins. Of the 50 patients, 38 (76%) completed 12 weeks of follow-up, 5 died, and 7 were lost to follow-up. Fasting lipid profile (TC, low-density lipoprotein, high-density lipoprotein, triglyceride) was measured <48 h, 4 weeks and 12 weeks following ictus. In patients who were statin naïve, there was a significant increase in TC at the week 12 evaluation. CONCLUSIONS: Cholesterol levels in acute stroke are an unreliable measure of lipid status. Initiation of statins should ideally be based on measurements taken 12 weeks after stroke.

Acute Disease↗
PubMed2005

Selection of thrombolytic therapy beyond 3 h using magnetic resonance imaging.

PURPOSE OF REVIEW: Use of intravenous thrombolytic therapy in ischaemic stroke is restricted to a 3-h time window because of the proof of this time window in pivotal clinical trials. Thrombolysis is aimed at recanalization of occluded arteries and reperfusion of the ischaemic penumbra, a region of critically hypoperfused, functionally impaired, but potentially viable brain. There are a number of current prospective trials that are testing the hypothesis that the presence of the penumbra will predict thrombolytic responders beyond 3 h. RECENT FINDINGS: Using magnetic resonance imaging, a mismatch between a larger perfusion-weighted imaging lesion and smaller diffusion-weighted imaging lesion is considered to represent the ischaemic penumbra. Perfusion-weighted imaging provides semiquantitative cerebral blood flow imaging and diffusion-weighted imaging is an index of the largely irreversible ischaemic core. This definition has been modified with the recognition that the perfusion-weighted imaging lesion includes benign oligaemia and that a portion of the diffusion-weighted imaging core is potentially salvageable with rapid reperfusion. Most acute stroke patients have a magnetic resonance imaging-penumbral signature within 6 h of stroke onset. The penumbra is commonly, but not invariably, associated with proximal arterial occlusion and is time-dependent. Preliminary studies have shown benefit from thrombolytic therapy beyond the established 3-h window. SUMMARY: Penumbral imaging using magnetic resonance imaging with perfusion over diffusion weighted imaging mismatch can provide a physiological 'tissue clock' in individual patients. Based on this hypothesis, a number of prospective trials are being performed. These include EPITHET, DEFUSE, DIAS, MR RESCUE and ROSIE.

Brain↗
PubMed2004

Insular cortical ischemia is independently associated with acute stress hyperglycemia.

BACKGROUND AND PURPOSE: Acute poststroke hyperglycemia has been associated with larger infarct volumes and a cortical location, regardless of diabetes status. Stress hyperglycemia has been attributed to activation of the hypothalamic-pituitary-adrenal axis but never a specific cortical location. We tested the hypothesis that damage to the insular cortex, a site with autonomic connectivity, results in hyperglycemia reflecting sympathoadrenal dysregulation. METHODS: Diffusion-weighted MRI, glycosylated hemoglobin (HbA1c), and blood glucose measurements were obtained in 31 patients within 24 hours of ischemic stroke onset. Acute diffusion-weighted imaging (DWI) lesion volumes were measured, and involvement of the insular cortex was assessed on T2-weighted images. RESULTS: Median admission glucose was significantly higher in patients with insular cortical ischemia (8.6 mmol/L; n=14) compared with those without (6.5 mmol/L; n=17; P=0.006). Multivariate linear regression demonstrated that insular cortical ischemia was a significant independent predictor of glucose level (P=0.001), as was pre-existing diabetes mellitus (P=0.008). After controlling for the effect of insular cortical ischemia, DWI lesion volume was not associated with higher glucose levels (P=0.849). There was no association between HbA1c and glucose level (P=0.737). CONCLUSIONS: Despite the small sample size, insular cortical ischemia appeared to be associated with the production of poststroke hyperglycemia. This relationship is independent of pre-existing glycemic status and infarct volume. Neuroendocrine dysregulation after insular ischemia may be 1 aspect of a more generalized acute stress response. Future studies of poststroke hyperglycemia should account for the effect of insular cortical ischemia.

Acute Disease↗
PubMed2004

Multicenter comparison of processes of care between Stroke Units and conventional care wards in Australia.

BACKGROUND AND PURPOSE: Approximately 23% of Australian hospitals provide Stroke Units (SUs). Evidence suggests that clinical outcomes are better in SUs than with conventional care. Reasons may include greater adherence to processes of care (PoC). The primary hypothesis was that adherence to selected PoC is greater in SUs than in other acute care models. METHODS: Prospective, multicenter, single-blinded design. Models of care investigated: SUs, mobile services, and conventional care. Selected PoC were related to care models and participant outcomes. Data were collected at acute hospitalization (median 9 days) and at medians of 8 and 28 weeks after stroke. RESULTS: 1701 patients were screened from 8 hospitals, 823 were eligible, and 468 participated. Response rate was 96% at final follow-up. Mean age was 73 years (SD 14). Overall PoC adherence rates for individual care models were SU 75%, mobile service 65%, and conventional care 52% (P<0.001). The adjusted odds of participants being alive at discharge if adhering to all or all but 1 PoC was significant (aOR 3.63; 95% CI: 1.04 to 12.66; P=0.043). Important trends at 28 weeks were found for being at home (aOR 3.09; 95% CI: 0.96 to 9.87; P=0.058) and independent (aOR 2.61; 95% CI: 0.96 to 7.10; P=0.061), with complete PoC adherence. CONCLUSIONS: Adherence to key PoC was higher in SUs than in other models. For all patients, adherence to PoC was associated with improved mortality at discharge and trends found with independence at home, providing support for the need to increase access to stroke units.

Aged↗
PubMed2004

Atheroma of the aortic arch: an important and poorly recognised factor in the aetiology of stroke.

Atrial fibrillation and severe carotid-artery stenosis are well-characterised risk factors for stroke; each is present in about a fifth of patients. The identification of such risk factors in patients is important because their presence calls for specific secondary prevention strategies. One region of the circulation that has received limited attention as a source of thrombus is the aortic arch. However, aortic arch atheroma is a common post-mortem finding, and it seems reasonable to speculate that atheroma might give rise to thrombi with distal embolism to the arterial tree, including the cerebral circulation. Here we review the evidence for aortic-arch atheroma as an important independent risk factor for stroke, and show that studies of the risk of stroke indicate a four times greater odds of stroke in patients with severe arch atheroma.

Aorta, Thoracic↗
PubMed2004

Advances in penumbra imaging with MR.

The concept of the ischaemic penumbra as critically hypoperfused and functionally impaired, but potentially viable brain, was introduced over 25 years ago. Recent studies have used a combination of perfusion-weighted magnetic resonance imaging (PWI) and diffusion-weighted imaging (DWI) to delineate the putative penumbra. PWI provides semiquantitative cerebral blood flow imaging and DWI is an index of the largely irreversible ischaemic core. PWI > DWI mismatch is an operational definition of the penumbra that was introduced in the late 1990s. This definition has been modified in recent years with the recognition that the PWI boundary includes a region of benign oligaemia and that a portion of the DWI core is potentially salvageable with rapid reperfusion. An MRI penumbral signature is present in the majority of patients within 6 h of stroke onset, often but not invariably associated with proximal arterial occlusion on magnetic resonance angiography, and is strictly time dependent. It has been postulated that penumbral imaging using MRI can provide a physiological 'tissue clock' and be used to predict benefit from thrombolytic therapy beyond the established 3-hour window. This has been suggested by pilot studies, but confirmation will rely on ongoing, prospective, randomized trials. The presence and extent of the penumbra may also predict the opportunity for tissue salvage with neuroprotection strategies. DWI and PWI parameters are being used in proof-of-principle stroke trials. Such trials can be performed with 100-200 patients randomized between treated and control groups and provide a biological signal of efficacy with only 10% of the sample size required for a Phase III study.

Brain Ischemia↗
PubMed2004

The use of PWI and DWI measures in the design of "proof-of-concept" stroke trials.

BACKGROUND AND PURPOSE: The authors used serial magnetic resonance perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) to determine whether major reperfusion and the attenuation of infarct expansion are associated with improved stroke outcome. METHODS: Forty-nine patients were studied with serial magnetic resonance imaging within 6 hours of stroke onset and again at 4 days (subacute studies) and 3 months (outcome studies). Two imaging parameters were examined: infarct expansion between acute and outcome studies and major reperfusion between acute and subacute studies. RESULTS: Patients with major reperfusion (45% of those with acute PWI lesions) were more likely to have little or no disability at outcome (National Institutes of Health Stroke Scale [NIHSS] score < or = 4, P = .0176; Barthel Index [BI] score > or = 90, P = .0547) after adjustment for baseline differences. In contrast, patients with infarct expansion (48%) were more likely to be dead or dependent at outcome (BI < 90, P = .0414; NIHSS score P = .082; modified Rankin Scale score > 2, P < .0001). These measures were used to generate sample size calculations based on hypothetical treatment effects. Therapies postulated to double the proportion of patients with major reperfusion from one third to two thirds would require 41 patients in each group (treated and untreated) to be sufficiently powered to show a difference. Interventions postulated to halve the number of patients with infarct expansion from 50% to 25% would require 66 patients in each group to show a difference. CONCLUSIONS: Infarct expansion and major reperfusion are associated with clinically meaningful changes in stroke outcome. These measures could be used as surrogate markers of outcome in late phase II proof-of-concept stroke studies designed to provide efficacy signals before embarking on large phase III studies with definitive clinical endpoints.

Adult↗