Search PubMed⌕ Search

Biomedical subjects

Steven R Levine

Publications and source records attributed to Steven R Levine.

At least 19 recordsLinked to original sources
PubMed2006

Association of serial biochemical markers with acute ischemic stroke: the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator Stroke Study.

BACKGROUND AND PURPOSE: Biochemical markers of acute neuronal injury may aid in the diagnosis and management of acute ischemic stroke. Serum samples from the National Institute for Neurological Disorders and Stroke (NINDS) recombinant tissue plasminogen activator Stroke Study were analyzed for the presence of 4 biochemical markers of neuronal, glial, and endothelial cell injury. These biochemical markers, myelin basic protein (MBP), neuron-specific enolase (NSE), S100beta, and soluble thrombomodulin, were studied for an association with initial stroke severity, infarct volume, and functional outcome. METHODS: In the original NINDS study, serum samples were drawn from all patients on presentation to the Emergency Department and at approximately 2 and 24 hours after initiation of study therapy. In this analysis, stored serum samples were available for 359 patients; 107 patients had samples for all 3 time points. Serum marker concentrations were measured by ELISA techniques. We examined the relation between serum concentrations of each marker and the degree of baseline neurological deficit, functional outcome, and infarct size on computed tomography at 24 hours and the effect of fibrinolytic therapy. RESULTS: Higher 24-hour peak concentrations of MBP, NSE, and S100beta were associated with higher National Institutes of Health Stroke Scale baseline scores (r=0.186, P<0.0001; r=0.117, P=0.032; and r=0.263, P<0.0001, respectively). Higher peak concentrations of MBP and S100beta (r=0.209, P<0.0001; r=0.239, P<0.0001) were associated with larger computed tomography lesion volumes. Patients with favorable outcomes had smaller changes in MBP and S100beta (P<0.05) concentrations in the first 24 hours. Soluble thrombomodulin was not associated with any severity or outcome measure. CONCLUSIONS: This study corroborates previous work demonstrating correlations of MBP, NSE, and S100beta with clinical and radiographic features in acute stroke. Despite significantly better outcomes in the tissue plasminogen activator-treated group, we found no difference in the early release of the 4 biomarkers between treatment groups. Further study will define the role of biomarkers in acute stroke management and prognostication.

Acute Disease↗
PubMed2006

Hemostatic activation and outcome after recombinant tissue plasminogen activator therapy for acute ischemic stroke.

BACKGROUND AND PURPOSE: Early thrombolytic therapy with intravenous recombinant tissue plasminogen activator (rtPA) improves clinical outcome in acute ischemic stroke (AIS), but impaired endogenous fibrinolysis, thrombin generation, and vascular injury may hamper the efficacy of thrombolysis. We investigated in an exploratory, post hoc analysis the relationship between hemostatic markers and clinical outcomes among patients included in the National Institute of Neurological Disorders and Stroke (NINDS) rtPA Stroke Study. METHODS: Tissue plasminogen activator (tPA) antigen, thrombin-antithrombin complex (TAT), soluble thrombomodulin, and fibrinogen levels were measured in patients with AIS included in the NINDS rtPA Stroke Study from plasma samples collected at baseline, at 2 hours after treatment, and after 24 hours. RESULTS: TAT and tPA antigen levels peaked at 2 hours selectively in the rtPA treatment group, whereas fibrinogen levels dropped at 2 hours and remained low after 24 hours (P<0.0001 for interaction effects between time and treatment). At 24 hours, higher levels of tPA antigen were associated with a lower chance of favorable outcome (odds ratio [OR]=0.34; 95% CI, 0.14 to 0.82) selectively in the rtPA group, and higher levels of TAT (OR=1.72; 95% CI, 1.26 to 2.34) in the entire cohort and of thrombomodulin selectively in the rtPA group (OR=4.45; 95% CI, 1.26 to 15.67) were associated with higher 3-month mortality. CONCLUSIONS: Hemostatic activation after AIS appears to be independently associated with clinical outcome in patients treated with rtPA. However, because we have tested for multiple associations, some may have been identified by chance alone and require further confirmatory studies. On the basis of this exploratory analysis, there is a rationale to investigate the safety and efficacy of protocols in which rtPA is complemented by agents that are antithrombotic and enhance fibrinolysis.

Acute Disease↗
PubMed2006

Predictors of ischemic stroke in the territory of a symptomatic intracranial arterial stenosis.

BACKGROUND: Antithrombotic therapy for intracranial arterial stenosis was recently evaluated in the Warfarin versus Aspirin for Symptomatic Intracranial Disease (WASID) trial. A prespecified aim of WASID was to identify patients at highest risk for stroke in the territory of the stenotic artery who would be the target group for a subsequent trial comparing intracranial stenting with medical therapy. METHODS AND RESULTS: WASID was a randomized, double-blinded, multicenter trial involving 569 patients with transient ischemic attack or ischemic stroke due to 50% to 99% stenosis of a major intracranial artery. Median time from qualifying event to randomization was 17 days, and mean follow-up was 1.8 years. Multivariable Cox proportional hazards models were used to identify factors associated with subsequent ischemic stroke in the territory of the stenotic artery. Subsequent ischemic stroke occurred in 106 patients (19.0%); 77 (73%) of these strokes were in the territory of the stenotic artery. Risk of stroke in the territory of the stenotic artery was highest with severe stenosis > or =70% (hazard ratio 2.03; 95% confidence interval 1.29 to 3.22; P=0.0025) and in patients enrolled early (< or =17 days) after the qualifying event (hazard ratio 1.69; 95% confidence interval 1.06 to 2.72; P=0.028). Women were also at increased risk, although this was of borderline significance (hazard ratio 1.59; 95% confidence interval 1.00 to 2.55; P=0.051). Location of stenosis, type of qualifying event, and prior use of antithrombotic medications were not associated with increased risk. CONCLUSIONS: Among patients with symptomatic intracranial stenosis, the risk of subsequent stroke in the territory of the stenotic artery is greatest with stenosis > or =70%, after recent symptoms, and in women.

Aged↗
PubMed2006

National Stroke Association guidelines for the management of transient ischemic attacks.

OBJECTIVE: Transient ischemic attacks are common and important harbingers of subsequent stroke. Management varies widely, and most published guidelines have not been updated in several years. We sought to create comprehensive, unbiased, evidence-based guidelines for the management of patients with transient ischemic attacks. METHODS: Fifteen expert panelists were selected based on objective criteria, using publication metrics that predicted nomination by practitioners in the field. Prior published guidelines were identified through systematic review, and recommendations derived from them were rated independently for quality by the experts. Highest quality recommendations were selected and subsequently edited by the panelists using a modified Delphi approach with multiple iterations of questionnaires to reach consensus on new changes. Experts were provided systematic reviews of recent clinical studies and were asked to justify wording changes based on new evidence and to rate the final recommendations based on level of evidence and quality. No expert was allowed to contribute to recommendations on a topic for which there could be any perception of a conflict of interest. RESULTS: Of 257 guidelines documents identified by systematic review, 13 documents containing 137 recommendations met all entry criteria. Six iterations of questionnaires were required to reach consensus on wording of 53 final recommendations. Final recommendations covered initial management, evaluation, medical treatment, surgical treatment, and risk factor management. INTERPRETATION: The final recommendations on the care of patients with transient ischemic attacks emphasize the importance of urgent evaluation and treatment. The novel approach used to develop these guidelines is feasible, allows for rapid updating, and may reduce bias.

Health Planning Guidelines↗
PubMed2006

Detection of carotid stenosis in African Americans with ischemic heart disease.

OBJECTIVES: This study was conducted to define the frequency of internal carotid stenosis in African American patients with ischemic heart disease (IHD). METHODS: We recruited 101 African American patients with IHD from a university medical center for carotid duplex examination. RESULTS: The frequency of >30%, >50%, and >70% stenosis was 21%, 11%, and 5%, respectively. Age >60 years (21% vs 3%, P < .01) and diabetes mellitus (22% vs 5%, P < .01) were predictors of unilateral stenosis of >50% and remained significant on multivariate testing. CONCLUSION: African American patients with established IHD have higher rates of extracranial carotid stenosis than community dwelling African American subjects and comparable rates with other populations.

Black or African American↗
PubMed2006

Lessons from adult stroke trials.

Before designing epidemiologic, genetic, or treatment trials in pediatric stroke, we should learn from adult trials which preceded. Adult trialists state that there is a need for improved animal models to mimic human disease. Dose-response curves with blinded outcome measures would improve preclinical data. Functional and histologic outcome measures would improve the animal model. In regard to human Phase 2 medication trials, safety, delivery, end points, and surrogate markers are necessary. The detection of biologic activity can be defined in Phase 2B trials. For Phase 3 trials, the experiment needs to be simple with global outcome measures as end points. New statistical designs such as futility analysis may improve and streamline trials in both adults and children. Clinical trials are a long process, and care needs to be incorporated at every step. Why is there a propensity of failed studies for acute ischemic stroke in adults? The reasons include (a) the animal model fails us, (b) the Phase 2 trials are ineffective in defining dose, and (c) the Phase 3 trials are poorly done. Because clinical trials, more often than not, fail to give positive (effective treatment) results, it seems reasonable to attempt to learn from others' past experiences before initiating pediatric stroke trials.

Adult↗
PubMed2006

Postpartum eclampsia complicated by reversible cerebral herniation.

BACKGROUND: Preeclampsia and eclampsia have been associated with significant morbidity and mortality. Posterior reversible encephalopathy syndrome is a neuroradiologic entity that has been previously reported to occur in patients with preeclampsia and eclampsia. We present, to our knowledge, the first reported case of late postpartum eclampsia complicated by posterior reversible encephalopathy syndrome and reversible cerebral herniation. CASE: A 39-year-old woman (para 1) presented with late postpartum preeclampsia on postpartum day 4. She developed eclampsia and posterior reversible encephalopathy syndrome, which was diagnosed by magnetic resonance imaging. She subsequently developed clinical and radiologic evidence of reversible cerebral herniation. CONCLUSION: Postpartum preeclampsia and eclampsia that is complicated by posterior reversible encephalopathy syndrome can result in cerebral herniation. Neuroradiologic imaging may be a useful adjunctive diagnostic tool in the setting of preeclampsia and eclampsia to predict disease severity.

Adult↗
PubMed2006

A web-based interactive database system for a transcranial Doppler ultrasound laboratory.

BACKGROUND: Variations in transcranial Doppler (TCD) examination performance techniques and interpretive paradigms between individual laboratories are a common challenge in the practice of TCD. Demand for rapid access to patient ultrasound examination data and report for use in intensive care settings has necessitated a more flexible approach to data management. Both of these issues may benefit from a computerized approach. METHODS: We describe the application of a World Wide Web-based database system for use in an ultrasound laboratory. Results. Databasing information while generating a TCD report is efficient. Web accessibility allows rapid and flexible communication of time-sensitive report information and interpretation for more expeditious clinical decision making. CONCLUSIONS: Web-based applications can extend the reach and efficiency of traditionally structured medical laboratories.

Cerebrovascular Disorders↗
PubMed2006

Neuropsychiatric disorders following vascular brain injury.

Several neuropsychiatric disorders such as mood, anxiety and psychotic disorders occur following cerebrovascular lesions. Post-stroke depression is the most common of these disorders and, along with post-stroke anxiety, has been shown to inhibit physical and cognitive recovery. Antidepressants have been shown to effectively treat post-stroke depression and to have a positive impact on rehabilitation efforts in patients suffering from this disorder. Much less is known about the potential impact of psychiatric conditions on recovery after stroke. Controlled trials will be able to adequately determine the effectiveness of treatment for these disorders.

Activities of Daily Living↗
PubMed2005

Importance of early ischemic computed tomography changes using ASPECTS in NINDS rtPA Stroke Study.

BACKGROUND AND PURPOSE: The importance of early ischemic change (EIC) on baseline computed tomography (CT) in the decision to thrombolyze the patient with acute ischemic stroke has been controversial. ASPECTS is a semiquantitative scale that scores the extent of EIC within the middle cerebral artery territory. We examined whether ASPECTS could be a treatment modifier by systematically reviewing the CT scans in the NINDS rtPA Stroke Study. METHODS: Six hundred eight of the 624 CT scans were available and of sufficient quality. One of 2 teams (n=3 each) of expert ASPECTS readers evaluated each scan for an ASPECTS value using a consensus score approach. Each team was blind to all clinical information except symptom side and blind to follow-up imaging and outcome information. ASPECTS values were stratified before analysis. Multivariable logistic regression was used to determine if an ASPECTS by treatment interaction existed on treatment response, outcome, and intracerebral hemorrhage risk. RESULTS: A total of 57.2% (348 of 608) of scans showed EIC with an ASPECTS <10. ASPECTS dichotomized into 8 to 10 and <8 did not have a treatment-modifying effect on good outcome but showed a trend to lower mortality at 90 days with tPA (relative risk 0.67, 95% confidence interval 0.41 to 1.06, P=0.10). ASPECTS 8 to 10 were associated with a trend to larger benefit of tPA with a number needed to treat (NNT) of 5 versus ASPECTS 3 to 7 with a NNT of 8. CONCLUSIONS: There was no evidence of treatment effect modification by the baseline ASPECTS value in the NINDS rtPA Stroke Study. Therefore, exclusion of patients for thrombolysis within 3 hours of symptom onset based on EIC is not supported by our data. There is a trend to reduced mortality and increased benefit to rtPA if the baseline CT scan is favorable (ASPECTS >7).

Aged↗
PubMed2005

Improved quality of stroke care for hospitalized Medicare beneficiaries in Michigan.

BACKGROUND AND PURPOSE: We reported previously that acute ischemic stroke patients encountered delays in obtaining neuroimaging and receiving thrombolysis, and that deep venous thrombosis prophylaxis was used only in a minority of eligible patients. We investigated whether these and other measures improved after a quality improvement initiative. METHODS: Medicare fee-for-service ischemic stroke and transient ischemic attack discharges in 136 acute care hospitals in Michigan were identified by International Classification of Diseases, 9th Revision, Clinical Modification codes. Only patients with stroke symptoms persisting for >1 hour and present on arrival were included in the analysis. Seven quality indicators were abstracted from chart review at baseline (discharges between July 1, 1998, and June 30, 1999) and at remeasurement (discharges between January 1, 2001, and June 30, 2001) after an intensive quality improvement initiative throughout Michigan hospitals. Quality indicators were compared at baseline and remeasurement. RESULTS: Indicators of care were determined in 5146 patients at baseline and 4980 patients on remeasurement. Four quality-of-care indicators showed significant improvement on remeasurement: antithrombotic prescribed at discharge (81.9 baseline versus 83.7% remeasurement; P=0.026), avoidance of sublingual nifedipine in patients with acute ischemic stroke (97.1 versus 99.7%; P<0.0001), documentation of a computed tomography (CT)/MRI during hospitalization (98.0 versus 99.1%; P=0.024), and appropriate deep venous thrombosis prophylaxis (13.8 versus 26.9%; P<0.0001). Time to CT/MRI did not significantly change, but time to thrombolysis improved (113 versus 88.5 minutes; P=0.045). CONCLUSIONS: Improvement occurred in several indicators of quality of care in Michigan Medicare beneficiaries presenting with acute stroke symptoms.

Administration, Sublingual↗
PubMed2005

Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis.

BACKGROUND: Atherosclerotic intracranial arterial stenosis is an important cause of stroke. Warfarin is commonly used in preference to aspirin for this disorder, but these therapies have not been compared in a randomized trial. METHODS: We randomly assigned patients with transient ischemic attack or stroke caused by angiographically verified 50 to 99 percent stenosis of a major intracranial artery to receive warfarin (target international normalized ratio, 2.0 to 3.0) or aspirin (1300 mg per day) in a double-blind, multicenter clinical trial. The primary end point was ischemic stroke, brain hemorrhage, or death from vascular causes other than stroke. RESULTS: After 569 patients had undergone randomization, enrollment was stopped because of concerns about the safety of the patients who had been assigned to receive warfarin. During a mean follow-up period of 1.8 years, adverse events in the two groups included death (4.3 percent in the aspirin group vs. 9.7 percent in the warfarin group; hazard ratio for aspirin relative to warfarin, 0.46; 95 percent confidence interval, 0.23 to 0.90; P=0.02), major hemorrhage (3.2 percent vs. 8.3 percent, respectively; hazard ratio, 0.39; 95 percent confidence interval, 0.18 to 0.84; P=0.01), and myocardial infarction or sudden death (2.9 percent vs. 7.3 percent, respectively; hazard ratio, 0.40; 95 percent confidence interval, 0.18 to 0.91; P=0.02). The rate of death from vascular causes was 3.2 percent in the aspirin group and 5.9 percent in the warfarin group (P=0.16); the rate of death from nonvascular causes was 1.1 percent and 3.8 percent, respectively (P=0.05). The primary end point occurred in 22.1 percent of the patients in the aspirin group and 21.8 percent of those in the warfarin group (hazard ratio, 1.04; 95 percent confidence interval, 0.73 to 1.48; P=0.83). CONCLUSIONS: Warfarin was associated with significantly higher rates of adverse events and provided no benefit over aspirin in this trial. Aspirin should be used in preference to warfarin for patients with intracranial arterial stenosis.

Adult↗