A Clinical Trial Comparing Smoking Cessation Interventions at Two Levels of Intensity in Stroke Patients, Stratified by the Presence of Insular Cortex Lesions.

INTRODUCTION: Smoking is a stroke risk factor but the most efficient way to promote cessation is unknown. The smoking behavior in patients during the first 2 years post-stroke is studied comparing brief advice and intensive behavioral counseling interventions, taking into consideration biological, psychological, and social factors. METHODS: Randomized clinical trial of 196 stroke patients, stratified by the presence or not of an insular cortex lesion, with two levels of smoking cessation intervention. RESULTS: The study retention rate was 85.2%. Abstinence point prevalence at three months after stroke was 50% in the brief advice group and 51.7% in the intensive behavioral counseling group (p = .82) and at 24 months, 48.3% in the brief group and 47.5% in the intensive group (p = .92). Most relapses occurred in the first weeks. After 3 months the curves separated with fewer events in the intensive group and at 24 months the Hazard Ratio was 0.91 (95% CI = 0.61 to 1.37; p = .67). Twenty-four months after stroke, patients with an insular lesion were more likely to be abstinent (OR 3.60, 95% CI = 1.27 to 10.14), as were those who lived with a partner (OR 2.31, 95% CI = 1.17 to 4.55) and those who were less dependent (OR 0.84, 95% CI = 0.73 to 0.97). CONCLUSIONS: A high percentage of patients gave up smoking in both intervention groups with no significant differences between the two. The effect of the insular lesion on smoking cessation, which is early and continued after two years, is particularly notable. IMPLICATIONS: This two-year clinical trial compares for the first time the efficacy of two different intensities of smoking cessation intervention in stroke patients, taking into consideration the effect of the insula. Good results are obtained both in the short and medium-term in people with stroke, especially when this is accompanied by an insular cortex lesion, but there is no evidence that better results are obtained with longer, more time-intensive, and possibly more costly follow-ups obtain better results than are obtained with briefer interventions.

Outcome assessment by central adjudicators in randomised stroke trials: Simulation of differential and non-differential misclassification.

INTRODUCTION: Adjudication of the primary outcome in randomised trials is thought to control misclassification. We investigated the amount of misclassification needed before adjudication changed the primary trial results.Patients (or materials) and methods: We included data from five randomised stroke trials. Differential misclassification was introduced for each primary outcome until the estimated treatment effect was altered. This was simulated 1000 times. We calculated the between-simulation mean proportion of participants that needed to be differentially misclassified to alter the treatment effect. In addition, we simulated hypothetical trials with a binary outcome and varying sample size (1000-10,000), overall event rate (10%-50%) and treatment effect (0.67-0.90). We introduced non-differential misclassification until the treatment effect was non-significant at 5% level. RESULTS: For the five trials, the range of unweighted kappa values were reduced from 0.89-0.97 to 0.65-0.85 before the treatment effect was altered. This corresponded to 2.1%-6% of participants misclassified differentially for trials with a binary outcome. For the hypothetical trials, those with a larger sample size, stronger treatment effect and overall event rate closer to 50% needed a higher proportion of events non-differentially misclassified before the treatment effect became non-significant. DISCUSSION: We found that only a small amount of differential misclassification was required before adjudication altered the primary trial results, whereas a considerable proportion of participants needed to be misclassified non-differentially before adjudication changed trial conclusions. Given that differential misclassification should not occur in trials with sufficient blinding, these results suggest that central adjudication is of most use in studies with unblinded outcome assessment. CONCLUSION: For trials without adequate blinding, central adjudication is vital to control for differential misclassification. However, for large blinded trials, adjudication is of less importance and may not be necessary.

Outcome Assessment by Central Adjudicators Versus Site Investigators in Stroke Trials: A Systematic Review and Meta-Analysis.

Background and Purpose- In randomized stroke trials, central adjudication of a trial's primary outcome is regularly implemented. However, recent evidence questions the importance of central adjudication in randomized trials. The aim of this review was to compare outcomes assessed by central adjudicators with outcomes assessed by site investigators. Methods- We included randomized stroke trials where the primary outcome had undergone an assessment by site investigators and central adjudicators. We searched MEDLINE, EMBASE, CENTRAL (Cochrane Central Register of Controlled Trials), Web of Science, PsycINFO, and Google Scholar for eligible studies. We extracted information about the adjudication process as well as the treatment effect for the primary outcome, assessed both by central adjudicators and by site investigators. We calculated the ratio of these treatment effects so that a ratio of these treatment effects >1 indicated that central adjudication resulted in a more beneficial treatment effect than assessment by the site investigator. A random-effects meta-analysis model was fitted to estimate a pooled effect. Results- Fifteen trials, comprising 69 560 participants, were included. The primary outcomes included were stroke (8/15, 53%), a composite event including stroke (6/15, 40%) and functional outcome after stroke measured on the modified Rankin Scale (1/15, 7%). The majority of site investigators were blind to treatment allocation (9/15, 60%). On average, there was no difference in treatment effect estimates based on data from central adjudicators and site investigators (pooled ratio of these treatment effects=1.02; 95% CI, [0.95-1.09]). Conclusions- We found no evidence that central adjudication of the primary outcome in stroke trials had any impact on trial conclusions. This suggests that potential advantages of central adjudication may not outweigh cost and time disadvantages in stroke studies if the primary purpose of adjudication is to ensure validity of trial findings.

Cost-Utility Analysis of Magnetic Resonance Imaging Management of Patients with Acute Ischemic Stroke in a Spanish Hospital.

INTRODUCTION: Stroke has a high rate of long-term disability and mortality and therefore has a significant economic impact. The objective of this study was to determine from a social perspective, the cost-utility of magnetic resonance imaging (MRI) compared to computed tomography (CT) as the first imaging test in acute ischemic stroke (AIS). METHODS: A cost-utility analysis of MRI compared to CT as the first imaging test in AIS was performed. Economic evaluation data were obtained from a prospective study of patients with AIS ≤12 h from onset in one Spanish hospital. The measure of effectiveness was quality-adjusted life-years (QALYs) calculated from utilities of the modified Rankin Scale. Both hospital and post-discharge expenses were included in the costs. The incremental cost-effectiveness ratio (ICER) was calculated and sensitivity analysis was carried out. The costs were expressed in Euros at the 2004 exchange rate. RESULTS: A total of 130 patients were analyzed. The first imaging test was CT in 87 patients and MRI in 43 patients. Baseline variables were similar in the two groups. The mean direct cost was €5830.63 for the CT group and €5692.95 for the MRI group (P = not significant). The ICER was €11,868.97/QALY. The results were sensitive when the indirect costs were included in the analysis. CONCLUSION: Total direct costs and QALYs were lower in the MRI group; however, this difference was not statistically significant. MRI was shown to be a cost-effective strategy for the first imaging test in AIS in 22% of the iterations according to the efficiency threshold in Spain.

Neurological tests for functional outcome assessment in rodent models of ischaemic stroke.

A critical aspect in all models is the assessment of the final outcome of the modelling procedure. In the case of a focal ischaemic brain injury, apart from the determination of the size of the lesion, another valuable tool is the evaluation of the final functional deficit. Indeed, ischaemic damage leads to the appearance of different degrees of sensoriomotor and cognitive impairments, which may yield useful information on location and size of the lesion and on the efficacy of neuroprotective treatments after the acute injury. In addition, the magnitude of these impairments may also be useful to predict final outcome and to evaluate neuro-restorative therapies in a long-term scenario. To this aim, a wide range of tests has been developed which allow the quantification of all these neurological symptoms. This review intends to compile the most useful behavioural tests designed to assess neurological symptoms in studies of focal experimental cerebral ischemia in rodents induced by middle cerebral artery occlusion, the most commonly used model of ischaemic stroke.

Perfusion-CT assessment of infarct core and penumbra: receiver operating characteristic curve analysis in 130 patients suspected of acute hemispheric stroke.

BACKGROUND AND PURPOSE: Different definitions have been proposed to define the ischemic penumbra from perfusion-CT (PCT) data, based on parameters and thresholds tested only in small pilot studies. The purpose of this study was to perform a systematic evaluation of all PCT parameters (cerebral blood flow, volume [CBV], mean transit time [MTT], time-to-peak) in a large series of acute stroke patients, to determine which (combination of) parameters most accurately predicts infarct and penumbra. METHODS: One hundred and thirty patients with symptoms suggesting hemispheric stroke < or =12 hours from onset were enrolled in a prospective multicenter trial. They all underwent admission PCT and follow-up diffusion-weighted imaging/fluid-attenuated inversion recovery (DWI/FLAIR); 25 patients also underwent admission DWI/FLAIR. PCT maps were assessed for absolute and relative reduced CBV, reduced cerebral blood flow, increased MTT, and increased time-to-peak. Receiver-operating characteristic curve analysis was performed to determine the most accurate PCT parameter, and the optimal threshold for each parameter, using DWI/FLAIR as the gold standard. RESULTS: The PCT parameter that most accurately describes the tissue at risk of infarction in case of persistent arterial occlusion is the relative MTT (area under the curve=0.962), with an optimal threshold of 145%. The PCT parameter that most accurately describes the infarct core on admission is the absolute CBV (area under the curve=0.927), with an optimal threshold at 2.0 ml x 100 g(-1). CONCLUSIONS: In a large series of 130 patients, the optimal approach to define the infarct and the penumbra is a combined approach using 2 PCT parameters: relative MTT and absolute CBV, with dedicated thresholds.