Carole L. White

The Secondary Prevention of Small Subcortical Strokes (SPS3) study.

Background Small subcortical strokes, also known as lacunar strokes, comprise more than 25% of brain infarcts, and the underlying vasculopathy is the most common cause of vascular cognitive impairment. How to optimally prevent stroke recurrence and cognitive decline in S3 patients is unclear. The aim of the Secondary Prevention of Small Subcortical Strokes study (Trial registration: NCT00059306) is to define strategies for reducing stroke recurrence, cognitive decline, and major vascular events. Methods Secondary Prevention of Small Subcortical Strokes is a randomised, multicentre clinical trial (n=3000) being conducted in seven countries, and sponsored by the US NINDS/NIH. Patients with symptomatic small subcortical strokes in the six-months before and an eligible lesion on magnetic resonance imaging are simultaneously randomised, in a 2 × 2 factorial design, to antiplatelet therapy – 325 mg aspirin daily plus 75 mg clopidogrel daily, vs. 325 mg aspirin daily plus placebo, double-blind – and to one of two levels of systolic blood pressure targets –‘intensive’ (<130 mmHg) vs. ‘usual’ (130–149 mmHg). Participants are followed for an average of four-years. Time to recurrent stroke (ischaemic or haemorrhagic) is the primary outcome and will be analysed separately for each intervention. The secondary outcomes are the rate of cognitive decline and major vascular events. The primary and most secondary outcomes are adjudicated centrally by those unaware of treatment assignment. Conclusions Secondary Prevention of Small Subcortical Strokes will address several important clinical and scientific questions by testing two interventions in patients with recent magnetic resonance imaging-defined lacunar infarcts, which are likely due to small vessel disease. The results will inform the management of millions of patients with this common vascular disorder.

Localizing value of α-methyl-L-tryptophan PET in intractable epilepsy of neocortical origin

Background: [11C] α-methyl-l-tryptophan (α-MTrp) has been developed as a tracer for the study of the synthesis of serotonin in the brain with PET. However, it has been shown that in pathologic conditions the tracer may reflect the activation of kynurenine metabolism. Increased levels of serotonin and quinolinic acid have been described in resected epileptogenic cortex, raising the possibility that α-MTrp can localize seizure foci in patients with intractable partial epilepsy. The authors assessed the uptake of α-MTrp in 18 patients (11 men, mean ± SD age 27.1 ± 10.1 years, range 13 to 54) with intractable partial epilepsy to correlate the PET findings with the epileptogenic area defined by electroclinical and neuroimaging data. Method: Seven patients with cortical dysplasia (CD) and 11 with partial epilepsy in which conventional MRI and fluorine-18-deoxyglucose (18FDG)-PET studies failed to detect any abnormality were studied. All underwent scalp EEG monitoring during the PET scan to exclude ictal events and estimate the interictal epileptic activity. Results: In seven patients (39%; CD four and cryptogenic partial epilepsy three), PET showed focal increased uptake of α-MTrp corresponding to the epileptogenic area. α-MTrp uptake in the epileptic focus correlated with the frequency of interictal spikes (r = 0.7, p < 0.05). Conclusions: α-MTrp-PET may be of value in the localization of the epileptogenic area not only in patients with visible dysplastic lesions, but also in those with cryptogenic partial epilepsy.

Toward a model of quality of life for family caregivers of stroke survivors.

The important role of family caregivers in maintaining their disabled and elderly members in the community is becoming increasingly recognized. Caregiver research, for the most part, has explored burden and emotional distress as outcomes of the caregiving experience. Although there is a growing consensus among health-care researchers concerning the importance of quality of life (QoL) as an outcome, there is little research examining QoL of family caregivers. The purpose of this paper, therefore, was to construct a conceptual framework from which to study the QoL of family caregivers of stroke survivors. Findings from a review of studies addressing the QoL of these caregivers guided the development of the model. The components of the model include the caregiving situation, characteristics of the caregiver, and environmental factors, and their proposed relationships with QoL. This model provides a framework for investigating how the caregiving experience impacts on the caregivers QoL.

Long-term caregiving after stroke: the impact on caregivers' quality of life.

This study examined the health-related quality of life (HRQL) and overall quality of life (QOL) of family caregivers of stroke survivors to determine changes over time and to identify QOL predictors. Caregivers were interviewed after 1.5 and 2 years of caregiving. The scores on the mental subscales were significantly lower than on the age- and sex-matched population norms. The most important predictors of QOL were the stroke survivors behavioral disturbances and reintegration into normal patterns of living. Caregivers who reported fewer stroke-survivor behavioral disturbances and well-adjusted reintegration also reported a higher personal QOL. These results highlight the impact of a stroke on the caregivers HRQL and QOL, even after 2 years, and the importance of interventions for caregivers.

Early progression of traumatic cerebral contusions: characterization and risk factors.

BACKGROUND Traumatic intracerebral contusions carry a high rate of early progression and are associated with morbidity and mortality. Our objectives were to better characterize the prevalence of progression of traumatic contusions, risk factors, and the association with outcome. METHODS Participants were 46 patients with traumatic intracerebral contusion who underwent a repeat computed tomography (CT) scan within 24 hours of injury. Hemorrhage volume on the CT scan was quantified using the ABC/2 technique. Univarite and multivariate statistics were used to define growth (percentage increase and absolute volume increase), to examine the relationship between the risk factors of interest and hemorrhage expansion, and with neurologic function and discharge destination. RESULTS Sixty-five percent of the patients experienced progression in the size of the lesion in the initial 24 hours postinjury. The international normalized ratio was significantly higher in the group that demonstrated progression. Deterioration on the Glasgow Coma Score was associated with a threefold risk of hemorrhage expansion being found on the CT as defined by percentage increase (odds ratio [OR] = 3.43; 95% confidence interval [CI]: 0.90 to 13.10) and similarly when defined as absolute increase in volume (OR = 3.32; 95% CI: 0.96 to 11.41). Controlling for injury severity, there was an association between hemorrhage growth and death with those displaying progression more likely to die during hospitalization (OR = 1.08; 95% CI: 0.97 to 1.20). CONCLUSION A high proportion of intracerebral contusions evolve in size very early in the postinjury period and are associated with negative outcomes. There is still not a proven therapy for limiting the expansion although the association of an elevated international normalized ratio with expansion suggests that coagulation abnormalities must be actively corrected.

Changing pain management practice and impacting on patient outcomes.

Concerns about acute pain management prompted the development of a pain management program. The program, with assessment, intervention, and evaluation components, was introduced by the clinical nurse specialist (CNS) in collaboration with a multidisciplinary team. The assessment phase included a descriptive study of postoperative pain and a baseline audit of nursing documentation related to pain assessment and management. Interventions, including a focused educational program and new routes for postoperative analgesia, were then introduced. Evaluations at 3 months and 2 years indicated improvements in documentation of pain assessments and improved management of pain. Additionally, at each follow-up evaluation, patients reported decreased postoperative pain. The assessment and management of pain is an important domain of nursing practice. The CNS is in a unique position to influence nursing practice and to impact on patient outcomes in this area of pain management.

Strategies to increase research-based practice: interplay with unit culture.

Purpose: A major focus of clinical nurse specialist nursing practice is the integration of research findings into practice. The purpose of this study was to describe strategies used to facilitate research utilization (RU) by nurses in a practice setting. Design: This multiple-case study identified the strategies that clinical nurse specialists and masters degree-prepared nurse educators, working collaboratively, used to facilitate RU. Setting/Sample: The setting included 8 units in 4 sites of a university hospital with all willing nurses participating. Methods: Open-ended focus groups and individual interviews and observational sessions were conducted using investigator-designed interview guides. Comprehensive qualitative analysis led to identification of categories and themes related to RU and the unit culture that supported it. Findings: Findings demonstrated that strategies to facilitate RU by staff at the unit level included conducting original research, supporting nurses participating in research, assessing and meeting staff learning needs, promoting staff attendance at conferences, stimulating goal-setting for presentations and publications, encouraging and responding to new ideas, questioning practice and stimulating inquiry, capitalizing on expertise in research knowledge and skills, and generating information and material resources. Characteristics of unit culture were linked to varying degrees of success with these strategies. The interplay of strategies with unit culture and research-based practice is described. Conclusion: A wide repertoire of strategies is needed to facilitate RU, and the outcome of these strategies is influenced by the unit culture. Implications for Practice: Consideration of the findings and the scope of the strategies used by nurses in the study can help clinical nurse specialist and other nursing leaders facilitate the building of practice on research.

C-Reactive Protein as a Prognostic Marker After Lacunar Stroke Levels of Inflammatory Markers in the Treatment of Stroke Study

Background and Purpose— Inflammatory biomarkers predict incident and recurrent cardiac events, but their relationship to stroke prognosis is uncertain. We hypothesized that high-sensitivity C-reactive protein (hsCRP) predicts recurrent ischemic stroke after recent lacunar stroke. Methods— Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) was an international, multicenter, prospective ancillary biomarker study nested within Secondary Prevention of Small Subcortical Strokes (SPS3), a phase III trial in patients with recent lacunar stroke. Patients were assigned in factorial design to aspirin versus aspirin plus clopidogrel, and higher versus lower blood pressure targets. Patients had blood samples collected at enrollment and hsCRP measured using nephelometry at a central laboratory. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for recurrence risks before and after adjusting for demographics, comorbidities, and statin use. Results— Among 1244 patients with lacunar stroke (mean age, 63.3±10.8 years), median hsCRP was 2.16 mg/L. There were 83 recurrent ischemic strokes (including 45 lacunes) and 115 major vascular events (stroke, myocardial infarction, and vascular death). Compared with the bottom quartile, those in the top quartile (hsCRP >4.86 mg/L) were at increased risk of recurrent ischemic stroke (unadjusted HR, 2.54; 95% CI, 1.30–4.96), even after adjusting for demographics and risk factors (adjusted HR, 2.32; 95% CI, 1.15–4.68). hsCRP predicted increased risk of major vascular events (top quartile adjusted HR, 2.04; 95% CI, 1.14–3.67). There was no interaction with randomized antiplatelet treatment. Conclusions— Among recent lacunar stroke patients, hsCRP levels predict the risk of recurrent strokes and other vascular events. hsCRP did not predict the response to dual antiplatelets. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

Rationale, Design, and Implementation of Aggressive Risk Factor Management in the Stenting and Aggressive Medical Management for Prevention of Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) Trial

The value of comprehensive intensive atherosclerotic risk factor control in patients with coronary artery disease is well established. In 2007, the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial demonstrated that among patients with stable coronary disease, intensive management of vascular risk factors was as good as endovascular intervention plus intensive medical management for preventing cardiac ischemic events.1 Yet, despite the fact that atherosclerotic risk factor control in patients with stroke or transient ischemic attack is recommended by guidelines,2 a multimodal approach to prevention has not previously been tested in patients with atherosclerotic stroke. Older atherosclerotic stroke prevention trials comparing carotid revascularization with medical therapy, such as North American Symptomatic Carotid Endarterectomy Trial (NASCET)3 and Asymptomatic Carotid Atherosclerosis Study (ACAS),4 were performed in an era before statins and angiotensin converting enzyme inhibitors became standard of care, and therefore risk factor control was not adequate by today’s standards. Even recent trials comparing carotid revascularization procedures5,6 had little emphasis on risk factor control in their design and therefore had little impact on blood pressure and cholesterol measures at 1 year.7,8 Among stroke prevention trials in patients with heterogeneous causes of stroke, several trials have studied the effects of specific risk factor medications9–11 or of intensive control of a particular risk factor, such as blood pressure,12 but no stroke prevention trials have used a mutimodal aggressive risk factor approach. Among patients with intracranial atherosclerosis, which may be the most common cause of stroke worldwide,13 risk factor control is also believed to be important for stroke prevention. The Warfarin Aspirin Symptomatic Intracranial Disease (WASID) trial, in which patients with symptomatic intracranial stenosis were managed with either warfarin or aspirin and usual risk factor management,14 showed that …

The correlates and course of depression in patients with lacunar stroke: Results from the secondary prevention of small subcortical strokes (SPS3) study

Background: Little is known about post-stroke depression in patients with lacunar stroke due to cerebral small vessel disease. Our objectives were to describe the prevalence of depression, its correlates and to examine the course of depression over time in a cohort of patients with lacunar stroke, the majority of whom had mild functional disability. Methods: Depression was determined in participants in the international Secondary Prevention of Small Subcortical Strokes (SPS3) trial which is testing antiplatelet therapies and targets of blood pressure control in patients with lacunar strokes and assessing stroke recurrence and cognitive decline. Depression was evaluated using the Patient Health Questionnaire. Multivariable logistic regression models were fitted to examine the relationship between the covariates of interest and depression. Generalized estimating equations were used to examine the likelihood of depression over time, while accounting for the multiple measurements within each subject. Results: The prevalence of depression in 2,477 participants at approximately 4 months after stroke was 19%. Older age (OR 0.97; 95% CI 0.96–0.99), male gender (OR 0.62; 95% CI 0.48–0.80) and less cognitive impairment (OR 0.99; 95% CI 0.98–1.00) were independently associated with a lower risk of depression. Functional disability (OR 1.8; 95% CI 1.3–2.4), living with a spouse/family (OR 1.6; 95% CI 1.1–2.3) and risk factors for stroke (OR 1.2; 95% CI 1.0–1.3) were each independently associated with a higher risk of depression. Longitudinal modeling indicated that the likelihood of depression decreased by 1.12 times (95% CI 1.06–1.17) for each 1-year increase in time. Conclusions: One fifth of those in the SPS3 trial cohort reported depression that is sustained over time. Although this is lower than the prevalence reported for stroke in general, these results underscore the importance of early screening for post-stroke depression, treatment and follow-up to minimize the negative consequences associated with depression.