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Background: Comparing patterns of resource utilization between hospitals is often complicated by biases in community and patient populations. Stroke patients treated with tissue plasminogen activator (tPA) provide a particularly homogenous population for comparison because of strict eligibility criteria for treatment. We tested whether resource utilization would be similar in this homogenous population between two hospitals located in a single Midwestern US community by comparing use of diagnostic testing and associated outcomes following treatment with t-PA., Methods: Medical records from 206 consecutive intravenous t-PA-treated stroke patients from two teaching hospitals (one university, one community-based) were reviewed. Patient demographics, clinical characteristics and outcome were analyzed, as were the frequency of use of CT, MRI, MRA, echocardiography, angiography, and EEG., Results: Seventy-nine and 127 stroke patients received t-PA at the university and community hospitals, respectively. The two patient populations were demographically similar. There were no differences in stroke severity. All outcomes were similar at both hospitals. Utilization of CT scans, and non-invasive carotid and cardiac imaging studies were similar at both hospitals; however, brain MR, TEE, and catheter angiography were used more frequently at the university hospital. EEG was obtained more often at the community hospital., Conclusions: Utilization of advanced brain imaging and invasive diagnostic testing was greater at the university hospital, but was not associated with improved clinical outcomes. This could not be explained on the basis of stroke severity or patient characteristics. This variation of practice suggests substantial opportunities exist to reduce costs and improve efficiency of diagnostic resource use as well as reduce patient exposure to risk from diagnostic procedures.

Introduction: The purpose of this study was to assess the agreement of Emergency Department (ED) attendings, ED residents, and neurology residents compared with stroke neurologists in the assessment of intravenous rt-PA eligibility., Methods: A convenience sample of patients presenting with possible stroke symptoms to the University of Michigan Hospital ED from June 2003 to July 2004 was identified. A physician from each of four groups: ED attending, ED resident, neurology resident, and stroke neurology attending independently evaluated each patient for eligibility for intravenous (i.v.) rt-PA. Accuracy, sensitivity, and positive predictive value (PPV) with 95% confidence intervals (CI) were calculated by physician type, compared with the stroke neurologist, for eligibility for i.v. rt-PA., Results: Exactly 36 (49%) out of the 73 evaluated patients were diagnosed with acute ischemic stroke and 11 were deemed eligible for treatment with i.v. tPA by the stroke neurologist. Agreement with the stroke neurologist for rt-PA eligibility was 93% [95% CI: 84%, 98%] (sensitivity = 82% [48%, 98%], PPV = 82% [48%, 99%]) for the ED attendings, 79% [65%, 90%] (sensitivity = 75% [35%, 97%], PPV = 43% [18% 71%]) for the ED residents, and 84% [73%, 92%] (sensitivity = 100% [74%, 100%], PPV = 52% [31%, 73%]) for the neurology residents. There were two false positive cases identified by ED attendings, eight, by ED residents, and 11 by neurology residents., Conclusions: This study suggests that the agreement between ED attendings and stroke neurologists for determination of rt-PA eligibility is good. There is room for improvement, however, in the determination of acute stroke therapy eligibility in the ED setting especially among trainees.

Background and Purpose: Obstructive sleep apnea (OSA) is common after acute ischemic stroke and predicts poor stroke recovery, but whether screening for OSA and treatment by continuous positive airway pressure (CPAP) improves neurological outcome is unknown. We used a cost-effectiveness model to estimate the magnitude of benefit that would be necessary to make polysomnography (PSG) and OSA treatment cost-effective in stroke patients., Methods: A decision tree modeled 2 alternative strategies: PSG followed by 3 months of CPAP for those found to have OSA versus no screening. The primary outcome was the utility gained through OSA screening and treatment in relation to 2 common willingness-to-pay thresholds of $50,000 and $100,000 per quality-adjusted life year (QALY)., Results: Screening resulted in an incremental cost-effectiveness ratio of $49,421 per QALY. Screening is cost-effective as long as the treatment of stroke patients with OSA by CPAP improves patient utilities by >0.2 for a willingness-to-pay of $50,000 per QALY and 0.1 for a willingness-to-pay of $100,000 per QALY., Conclusions: A clinical trial assessing the effectiveness of CPAP in improving stroke outcome is warranted from a cost-effectiveness standpoint.

Introduction: Modern management of acute stroke, including the use of tissue plasminogen activator (t-PA), requires hospitals to be better prepared for rapid diagnosis and treatment., Methods: Surveillance of practice of acute stroke treatment by Michigan hospitals was performed in 1998. We determined variation in hospital preparedness for treatment by number of emergency department visits. Factors associated with hospital use of t-PA were analyzed using logistic regression., Results: Surveys were returned by 97 (55%) hospitals. Hospitals with a greater number of emergency department visits were significantly more likely to have a clinical pathway, to have given t-PA, and to be better prepared for stroke treatment. After multivariate analysis, greater number of stroke patients per year (P < .001) and availability of skilled intensive care department staff (P = .056) were associated with hospital t-PA use., Conclusions: Specific hospital characteristics are associated with t-PA use. Consideration of these may be used to devise new strategies for improved delivery of acute stroke treatment.

Background: Menses is a theoretical contraindication to intravenous tissue plasminogen activator (tPA) treatment. We sought to establish the safety of intravenous tPA in the treatment of acute ischemic stroke in women who are actively menstruating., Summary of Report: We provide a case report and review of the National Institute of Neurological Disorders and Stroke (NINDS) database for women coded as actively menstruating. Nine subjects were coded as actively menstruating in the NINDS trial (4 placebo and 5 in the treatment). One subject in the treatment group who had a 1-year history of dysfunctional uterine bleeding required emergent uterine artery ligation. We also report a case of a woman requiring transfusion after intravenous tPA administration for acute ischemic stroke., Conclusions: Intravenous tPA may be administered relatively safely in women who are menstruating and should be used with caution in women with a history of dysfunctional uterine bleeding. Potential patients should be advised that they might require transfusion for increased menstrual flow.

Delayed patient presentation to the emergency department plays a major role in the underuse of tissue plasminogen activator (t-PA) for acute ischemic stroke, and multiple studies have been performed to examine factors that contribute to patient delay. Although many have hypothesized that educational interventions could increase the number of patients presenting in time to receive acute stroke therapy, only a handful of studies have examined the impact of such intervention on patient behavior. This article proposes that behavioral interventions for acute stroke can and should be designed and evaluated scientifically.

Background: No proven neuroprotective treatment exists for ischemic brain injury after cardiac arrest. Mild-to-moderate induced hypothermia (MIH) is effective in animal models., Methods and Results: A safety and feasibility trial was designed to evaluate mild-to-moderate induced hypothermia by use of external cooling blankets after cardiac arrest. Inclusion criteria were return of spontaneous circulation within 60 minutes of advanced cardiac life support, hypothermia initiated within 90 minutes, persistent coma, and lack of acute myocardial infarction or unstable dysrhythmia. Hypothermia to 33 degrees C was maintained for 24 hours followed by passive rewarming. Nine patients were prospectively enrolled. Mean time from advanced cardiac life support to return of spontaneous circulation was 11 minutes (range 3 to 30); advanced cardiac life support to initiation of hypothermia was 78 minutes (range 40 to 109); achieving 33 degrees C took 301 minutes (range 90 to 690). Three patients completely recovered, and 1 had partial neurological recovery. One patient developed unstable cardiac dysrhythmia. No other unexpected complications occurred., Conclusions: Mild-to-moderate induced hypothermia after cardiac arrest is feasible and safe. However, external cooling is slow and imprecise. Efforts to speed the start of cooling and to improve the cooling process are needed.

Acute ischemic stroke is a medical emergency that requires rapid evaluation and treatment. Prehospital and emergency department care can be streamlined to meet those goals. Intravenous rt-PA therapy improves outcome in selected patients with ischemic stroke if given within 3 hours of stroke onset, but offers no benefit beyond that time window. Intra-arterial thrombolytic therapy and intravenous defibrogenating agents may also be beneficial in selected patients. Newer thrombolytic agents such as aspirin and heparin in acute ischemic stroke treatment have been clarified by recent trials.

Background and Purpose: Nuclear factor-kappaB (NF-kappaB) is a ubiquitous transcription factor that, when activated, translocates to the nucleus, binds to DNA, and promotes transcription of many target genes. Its activation has been demonstrated in chronic inflammatory conditions, cerebral ischemia, and apoptotic cell death. The present study evaluated the presence and activation of NF-kappaB in relation to cell death surrounding intracerebral hemorrhage (ICH)., Methods: Striatal ICH was induced in rats by the double blood injection method. Animals were killed 2, 8, and 24 hours and 4 days after ICH. To examine changes in NF-kappaB protein, Western blot was performed on brain extract. We determined NF-kappaB activity using electrophoretic mobility shift assay (EMSA) and immunohistochemistry, using an antibody that only recognizes active NF-kappaB. DNA fragmentation was detected with terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL) staining., Results: Western blot analysis of the NF-kappaB p65 subunit showed that there was no difference in p65 protein levels in the control, 2-hour, 8-hour, or 24-hour groups. However, ipsilateral perilesional samples from the 4-day group revealed a 1.8- to 2.5-fold increase compared with the contralateral hemisphere. Western blotting showed no differences in the inhibitor of NF-kappaB, IkappaBalpha, in any group. EMSA showed 1.3-, 2.1-, and 3.6-fold increased NF-kappaB activation in the ipsilateral striatum from the 8-hour, 24-hour, and 4-day groups, respectively, compared with the contralateral hemisphere. Immunohistochemistry, in which an activation-dependent anti-NF-kappaB antibody was used, demonstrated perivascular NF-kappaB activation as early as 2 hours after ICH with more generalized activation at 8 hours, in agreement with the EMSA results. NF-kappaB activation colocalized to cells containing fragmented DNA measured by TUNEL., Conclusions: The present study suggests a relationship between NF-kappaB and the pathobiology of perilesional cell death after ICH.

Stroke is the leading cause of long term disability and the third leading cause of death in the US. Nearly $US40.9 billion (1997 values) are spent each year on direct and indirect stroke-related costs in the US alone. Length of hospital stay, hospital overheads and nursing-related and rehabilitation costs account for the majority of stroke-related expenditures. Intravenous recombinant tissue plasminogen activator (rt-PA) therapy for patients presenting within 3 hours from onset of ischaemic stroke was shown to improve outcome at 3 months by the National Institute of Neurological Disease and Stroke (NINDS) investigators using a dosage of 0.9 mg/kg. When the NINDS rt-PA Stroke Study results were examined using a Markov model, savings of $US4 to $US5 million (1996 values) per 1000 patients treated with rt-PA were projected. These savings were predicted to result from decreases in length of hospital stay, inpatient rehabilitation and nursing home costs, increases in the number of patients discharged directly to home and improvements in quality-adjusted life-years. Furthermore, a recent meta-analysis has documented that the institution of stroke units, consisting of multidisciplinary specialised stroke teams, also decreased length of hospital stay, death and dependency. Because only a minority of patients who have a stroke are currently eligible for thrombolysis, implementation of specialised and standardised stroke care may further enhance cost benefits and improve patient outcomes.

The concept of neuroprotection relies on the principle that delayed neuronal injury occurs after ischemia. The phenomenon of the "ischemic cascade" has been described, and each step along this cascade provides a target for therapeutic intervention. In animal models of global and focal cerebral ischemia, numerous preclinical studies have demonstrated various agents to be neuroprotective at different steps along this cascade. A wide variety of drugs has also been studied in humans. Ten classes of neuroprotective agents have reached phase III efficacy trials but have shown mixed results. They include calcium channel antagonists, NMDA receptor antagonists, lubeluzole, CDP-choline, the free radical scavenger tirilizad, anti-intercellular adhesion molecule-1 (ICAM-1) antibody, GM-1 ganglioside, clomethiazole, the sodium channel antagonist fosphenytoin, and piracetam. In the future, clinicians may have an armamentarium of treatments for acute ischemic stroke at their disposal, with a combination of agents directed at different sites in the ischemic cascade being the ultimate goal.