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Biomedical subjects

Thomas G Brott

Publications and source records attributed to Thomas G Brott.

18 recordsLinked to original sources
PubMed2004

Carotid revascularization for prevention of stroke: carotid endarterectomy and carotid artery stenting.

Carotid endarterectomy (CEA) has been used for the past several decades in patients with carotid occlusive disease. Large randomized controlled trials have documented that CEA is a highly effective stroke preventive among patients with carotid stenosis and recent transient ischemic attack or cerebral infarction. In asymptomatic patients with carotid stenosis, clinical trial data suggest that the degree of stroke prevention from CEA is less than among symptomatic patients. However, otherwise healthy men and women with an asymptomatic carotid stenosis of 60% or greater have a lower risk of future cerebral infarction, including disabling cerebral infarction, if treated with CEA compared with those treated with medical management alone. More recently, carotid artery stenting has been performed Increasingly for patients with carotid occlusive disease. As technology has improved, procedural risks have declined and are approaching those reported for CEA. The benefits and durability of CEA compared with carotid artery stenting are still unclear and are being studied in ongoing randomized controlled trials.

Aged↗
PubMed2003

Reliability of the questionnaire for verifying stroke-free status.

BACKGROUND: The Questionnaire for Verifying Stroke-Free Status (QVSS) is a practical instrument for confirming absence of previous symptomatic stroke or transient ischemic attack in control subjects participating in stroke research. METHODS: We tested reliability of telephone administration of the QVSS in stroke patients and healthy volunteers aged >/=50 years. For intrarater reliability, one interviewer administered the QVSS twice to the same subjects 8 weeks apart (115 subjects). For interrater reliability, one interviewer administered the QVSS and a different interviewer readministered the QVSS 8 weeks later (107 subjects). Both interviewer and interviewee were masked to responses from the first interview. RESULTS: Intrarater agreement for overall classification of stroke-free status was 0.90 [95% confidence interval (CI), 0.82-0.94], with a kappa of 0.78 (95% CI, 0.67-0.90). Interrater agreement for overall classification was 0.94 (95% CI, 0.88-0.98), with a kappa of 0.89 (95% CI, 0.80-0.97). CONCLUSION: The QVSS is a reliable instrument for telephone interviews in stroke research when applied to adult populations without severe deficits of cognition or verbal communication.

Aged↗
PubMed2003

The Ischemic Stroke Genetics Study (ISGS) Protocol.

BACKGROUND: The molecular basis for the genetic risk of ischemic stroke is likely to be multigenic and influenced by environmental factors. Several small case-control studies have suggested associations between ischemic stroke and polymorphisms of genes that code for coagulation cascade proteins and platelet receptors. Our aim is to investigate potential associations between hemostatic gene polymorphisms and ischemic stroke, with particular emphasis on detailed characterization of the phenotype. METHODS/DESIGN: The Ischemic Stroke Genetic Study is a prospective, multicenter genetic association study in adults with recent first-ever ischemic stroke confirmed with computed tomography or magnetic resonance imaging. Patients are evaluated at academic medical centers in the United States and compared with sex- and age-matched controls. Stroke subtypes are determined by central blinded adjudication using standardized, validated mechanistic and syndromic classification systems. The panel of genes to be tested for polymorphisms includes beta-fibrinogen and platelet glycoprotein Ia, Iba, and IIb/IIIa. Immortalized cell lines are created to allow for time- and cost-efficient testing of additional candidate genes in the future. DISCUSSION: The study is designed to minimize survival bias and to allow for exploring associations between specific polymorphisms and individual subtypes of ischemic stroke. The data set will also permit the study of genetic determinants of stroke outcome. Having cell lines will permit testing of future candidate risk factor genes.

Academic Medical Centers↗
PubMed2003

Familial clustering of stroke according to proband age at onset of presenting ischemic stroke.

BACKGROUND AND PURPOSE: The magnitude of inherited risk of stroke may lessen with age, and this would have implications for optimizing genomic approaches to identifying genetic risk factors for stroke. We investigated the relationship between age and inherited risk of stroke. METHODS: Family histories of stroke were obtained in systematic interviews with 310 adult men and women with recent CT- or MR-confirmed ischemic stroke. Probability of stroke in first-degree relatives was analyzed by logistic regression, adjusting for sibship size. RESULTS: The probability of having a sibling with stroke increased as proband age at stroke presentation increased. Per decade increase in proband age, the odds ratio was 1.65 (95% confidence interval [CI], 1.20 to 2.28; P=0.002) for a concordant sibling and 1.69 (95% CI, 1.15 to 2.49; P=0.008) for >or=2 first-degree relatives with a history of stroke. CONCLUSIONS: Clustering of stroke was not greater in families with probands manifesting symptoms of stroke in earlier than later adulthood. The relationship between proband age and positive family history of stroke does not suggest an upper age-limit cutoff for genomewide linkage studies.

Adult↗
PubMed2002

The Siblings With Ischemic Stroke Study (SWISS) protocol.

BACKGROUND: Family history and twins studies suggest an inherited component to ischemic stroke risk. Candidate gene association studies have been performed but have limited capacity to identify novel risk factor genes. The Siblings With Ischemic Stroke Study (SWISS) aims to conduct a genome-wide scan in sibling pairs concordant or discordant for ischemic stroke to identify novel genetic risk factors through linkage analysis. METHODS: Screening at multiple clinical centers identifies patients (probands) with radiographically confirmed ischemic stroke and a family history of at least 1 living full sibling with stroke. After giving informed consent, without violating privacy among other family members, the proband invites siblings concordant and discordant for stroke to participate. Siblings then contact the study coordinating center. The diagnosis of ischemic stroke in potentially concordant siblings is confirmed by systematic centralized review of medical records. The stroke-free status of potentially discordant siblings is confirmed by validated structured telephone interview. Blood samples for DNA analysis are taken from concordant sibling pairs and, if applicable, from 1 discordant sibling. Epstein-Barr virus-transformed lymphoblastoid cell lines are created, and a scan of the human genome is planned. DISCUSSION: Conducting adequately powered genomics studies of stroke in humans is challenging because of the heterogeneity of the stroke phenotype and the difficulty of obtaining DNA samples from clinically well-characterized members of a cohort of stroke pedigrees. The multicentered design of this study is intended to efficiently assemble a cohort of ischemic stroke pedigrees without invoking community consent or using cold-calling of pedigree members.

Journal Article↗
PubMed2002

Relative edema volume is a predictor of outcome in patients with hyperacute spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Little is known about the relationship between perihematomal edema in spontaneous intracerebral hemorrhage (ICH) and outcome. The purpose of this study was to determine whether absolute or relative edema volume (edema volume divided by hematoma volume) predicts mortality or functional outcome in patients with hyperacute spontaneous ICH. We hypothesized that increasing baseline relative edema volume is associated with greater probability of poor functional outcome. METHODS: This was a secondary analysis of a prospective, population-based study of hematoma growth in 142 patients with spontaneous ICH. Patients were imaged within 3 hours of onset, then 1 and 20 hours later. Our primary analysis excluded patients with anticoagulant use (n=7), underlying aneurysm/vascular malformation (n=9), trauma (n=1), incomplete data (n=20), infratentorial ICH (n=17), intraventricular extension (n=38), and no consent (n=2). We analyzed whether associations existed between baseline edema volumes or other clinical/radiological variables and either 12-week modified Rankin Scale score >2 or 30-day mortality. Secondary analyses used 20-hour CT scan data, all patients with supratentorial ICH, and 12-week Barthel Index score <85. RESULTS: By multivariable logistic regression analysis, baseline relative edema was the strongest independent predictor of functional outcome and was associated with lesser odds of poor 3-month functional outcome (odds ratio, 0.09 per 1.0-unit [100%] increase; 95% CI, 0.01 to 0.64; P=0.016) and 12-week Barthel Index score <85 (odds ratio, 0.12; 95% CI, 0.02 to 0.91; P=0.039) but did not predict mortality. Secondary analyses confirmed this result. Absolute edema volume predicted neither mortality nor functional outcome. CONCLUSIONS: Relative edema is strongly predictive of functional outcome in patients with hyperacute supratentorial spontaneous ICH without intraventricular extension.

Acute Disease↗
PubMed2002

Natural history of perihematomal edema in patients with hyperacute spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: The natural history of perihematomal edema in human hyperacute spontaneous intracerebral hemorrhage (ICH) has not been well described. METHODS: This study was a secondary analysis of a previously reported prospective, population-based study of hematoma growth in 142 patients with spontaneous ICH. Patients were first imaged within 3 hours of onset, then 1 and 20 hours later. We excluded patients with anticoagulant use (n=7), underlying aneurysm/vascular malformation (n=9), trauma (n=1), incomplete data (n=20), infratentorial ICH (n=17), and no consent (n=2), leaving an overall study population of 86 patients. From this overall group we further excluded patients with intraventricular extension (n=38), subsequent surgery (n=5), or death (n=2) before 20-hour postbaseline CT. This second, "restricted" analysis group of 41 patients was relatively devoid of clinical or radiological variables likely to confound edema measurement. Absolute and relative edema volumes (edema volume divided by hematoma volume) were descriptively summarized. Correlations between baseline edema volumes and relevant clinical and radiological variables were then performed. RESULTS: Overall, median absolute edema volume increased from 6.93 to 14.4 cm(3) during the first 24 hours after ICH, and median relative edema volume increased from 0.47 to 0.81. In the restricted group, median absolute edema volume was 7.4 cm(3) at baseline and 11.0 cm(3) at 24 hours after ICH, and median relative edema volume increased from 0.55 to 0.81. Baseline relative edema volume was significantly negatively correlated with subsequent change in relative edema volume from baseline to 20-hour CT (r=0.57, P=0.0002) but was not significantly correlated with other clinical and radiological variables, including hematoma volume or change in hematoma volume. CONCLUSIONS: Perihematomal edema volume increases by approximately 75% during the first 24 hours after hyperacute spontaneous ICH. Patients with the least amounts of baseline relative edema volume were most likely to develop significant additional amounts of edema during the first 24 hours after spontaneous ICH.

Acute Disease↗
PubMed2002

Thrombolytic treatment of acute ischemic stroke.

Intravenous recombinant tissue-type plasminogen activator is approved by the US Food and Drug Administration for treating acute ischemic stroke within 3 hours of onset of symptoms. Initiation of thrombolysis within 90 minutes of onset of symptoms is a treatment goal supported by current studies. Postmarketing data suggest that the risk of intracranial hemorrhage may be unacceptably high when recombinant tissue-type plasminogen activator is given to patients who would not have been eligible for enrollment in the pivotal phase 3 clinical trials. Further studies of local intra-arterial thrombolysis and improved selection of patients with advanced brain imaging are expected in the future, but the emphasis at present should be on rapid identification, evaluation, and treatment of appropriate patients with intravenous therapy.

Acute Disease↗
PubMed2001

Organizing the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST): National Institutes of Health, Health Care Financing Administration, and industry funding.

The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) is a prospective, randomized, multicenter clinical trial of carotid endarterectomy (CEA) versus carotid artery stenting (CAS) as prevention for stroke in patients with symptomatic stenosis greater than or equal to 50%. CREST is sponsored by the US National Institute of Neurological Disorders and Stroke (NINDS) of the US National Institutes of Health (NIH), with additional support by a device manufacturer, and will provide data to the US Food and Drug Administration (FDA) for evaluation of a stent device. Because of budget constraints for CREST, Health Care Financing Administration (HCFA) reimbursement for hospital costs incurred by CREST patients will be essential. The involvement of academic scientists, industry, and three separate government agencies (NIH, FDA, HCFA) has presented many challenges in conducting the trial. A review of the pathways followed to meet these challenges may be helpful to others seeking to facilitate sharing of the costs and burdens of conducting innovative clinical research.

Editorial↗
PubMedDate not supplied

Spouses and unrelated friends of probands as controls for stroke genetics studies.

To plan a multisite, ischemic stroke genetic study, stroke patients were surveyed about the availability and characteristics of a convenience sample of spouse/friend controls. 65% of all stroke-affected probands reported a living spouse. A more detailed survey was conducted at the University of Virginia, Charlottesville, Va., USA: 51% of stroke patients reported a living, stroke-free spouse who would be willing to serve as a control, and 49% reported having a stroke-free friend who would be willing to serve as a control. Overall, 75% of stroke patients reported at least 1 individual willing to participate as a control. Cases without an identified control were more likely to be non-white (48%) than were cases with a control (13%; p = 0.00004). Cases were older than controls (67.3 vs. 59.2 years; p = 0.000002), and a greater proportion of cases than controls were male (57 vs. 33%; p = 0.0002). Without proper attention to matching, the use of a spouse/friend convenience sample would result in imbalances in basic demographic characteristics.

Adult↗
PubMedDate not supplied

Creation of a bilingual Spanish-English version of the Questionnaire for Verifying Stroke-free Status.

Spanish-language versions of standardized questionnaires are important for facilitating inclusion of Hispanic populations in epidemiologic, genetic, and clinical studies. We aimed at producing a culturally adapted Spanish translation of the Questionnaire for Verifying Stroke-free Status (QVSS), an instrument used to screen for cerebrovascular end points and to ensure that subjects serving as controls in studies on stroke are indeed stroke free. Five professional translators and ten bilingual physicians independently translated the English-language version of the QVSS into Spanish. Blinded back-translation confirmed conceptual equivalence of the original English-language and final Spanish-language versions.

Concept Formation↗