Phillip A. Scott

Guidelines for the Early Management of Patients With Acute Ischemic Stroke A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

Background and Purpose— The authors present an overview of the current evidence and management recommendations for evaluation and treatment of adults with acute ischemic stroke. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators responsible for the care of acute ischemic stroke patients within the first 48 hours from stroke onset. These guidelines supersede the prior 2007 guidelines and 2009 updates. Methods— Members of the writing committee were appointed by the American Stroke Association Stroke Council’s Scientific Statement Oversight Committee, representing various areas of medical expertise. Strict adherence to the American Heart Association conflict of interest policy was maintained throughout the consensus process. Panel members were assigned topics relevant to their areas of expertise, reviewed the stroke literature with emphasis on publications since the prior guidelines, and drafted recommendations in accordance with the American Heart Association Stroke Council’s Level of Evidence grading algorithm. Results— The goal of these guidelines is to limit the morbidity and mortality associated with stroke. The guidelines support the overarching concept of stroke systems of care and detail aspects of stroke care from patient recognition; emergency medical services activation, transport, and triage; through the initial hours in the emergency department and stroke unit. The guideline discusses early stroke evaluation and general medical care, as well as ischemic stroke, specific interventions such as reperfusion strategies, and general physiological optimization for cerebral resuscitation. Conclusions— Because many of the recommendations are based on limited data, additional research on treatment of acute ischemic stroke remains urgently needed.

National Trends in Use of Computed Tomography in the Emergency Department

STUDY OBJECTIVE The role of computed tomography (CT) in acute illnesses has increased substantially in recent years; however, little is known about how CT use in the emergency department (ED) has changed over time. METHODS A retrospective study was performed with the 1996 to 2007 National Hospital Ambulatory Medical Care Survey, a large nationwide survey of ED services. We assessed changes during this period in CT use during an ED visit, CT use for specific ED presenting complaints, and disposition after CT use. Main outcomes were presented as adjusted risk ratios (RRs). RESULTS Data from 368,680 patient visits during the 12-year period yielded results for an estimated 1.29 billion weighted ED encounters, among which an estimated 97.1 million (7.5%) patients received at least one CT. Overall, CT use during ED visits increased 330%, from 3.2% of encounters (95% confidence interval [CI] 2.9% to 3.6%) in 1996 to 13.9% (95% CI 12.8% to 14.9%) in 2007. Among the 20 most common complaints presenting to the ED, there was universal increase in CT use. Rates of growth were highest for abdominal pain (adjusted RR comparing 2007 to 1996=9.97; 95% CI 7.47 to 12.02), flank pain (adjusted RR 9.24; 95% CI 6.22 to 11.51), chest pain (adjusted RR 5.54; 95% CI 3.75 to 7.53), and shortness of breath (adjusted RR 5.28; 95% CI 2.76 to 8.34). In multivariable modeling, the likelihood of admission or transfer after a CT scan decreased over the years but has leveled off more recently (adjusted RR comparing admission or transfer after CT in 2007 to 1996=0.42; 95% CI 0.32 to 0.55). CONCLUSION CT use in the ED has increased significantly in recent years across a broad range of presenting complaints. The increase has been associated with a decline in admissions or transfers after CT use, although this effect has stabilized more recently.

Initial clinical experience with IV tissue plasminogen activator for acute ischemic stroke: A multicenter survey

Article abstract We assessed initial clinical experience with IV tissue plasminogen activator (t-PA) treatment of acute ischemic stroke in a standardized retrospective survey of hospitals with experienced acute stroke treatment systems. The incidence of symptomatic intracerebral hemorrhage (ICH) was 6% (11 of 189 patients; 95% CI 3 to 11%), similar to that in the National Institute of Neurological Disorders and Stroke (NINDS) t-PA Stroke Study. Deviations from the NINDS protocol guidelines were identified in 30% of patients (56 of 189). The incidence of symptomatic ICH was 11% among patients with protocol deviations as compared with 4% in patients who were treated according to the NINDS protocol guidelines, suggesting that strict adherence to protocol guidelines is prudent.

Intravenous tissue plasminogen activator for acute ischemic stroke in patients aged 80 years and older: The tPA stroke survey experience

BACKGROUND AND PURPOSE Intravenous tissue plasminogen activator (tPA) administered within 3 hours of symptom onset is the first available effective therapy for acute ischemic stroke (AIS). Few data exist, however, on its use in very elderly patients. We examined the characteristics, complications, and short-term outcome of AIS patients aged >/=80 years treated with tPA. METHODS Patients aged >/=80 years (n=30) were compared with counterparts aged <80 years (n=159) included in the tPA Stroke Survey, a US retrospective survey of 189 consecutive AIS patients treated with intravenous tPA at 13 hospitals. RESULTS Risk of intracerebral hemorrhage (fatal, symptomatic, and total) was 3%, 3%, and 7% in the elderly age group and 2%, 6%, and 9%, respectively, in their younger counterparts (P=NS for all comparisons). Likelihood of favorable outcome, defined as modified Rankin score 0 to 1, National Institutes of Health Stroke Scale score </=5, or marked improvement by hospital discharge, was comparable between groups (37%, 54%, and 43% versus 30%, 54%, and 43%, respectively; P=NS for all comparisons). Elderly patients were more likely to be treated by stroke specialists (87% versus 60%; P=0.005) and less likely to have an identified protocol deviation (13% versus 33%; P=0.03). Elderly patients were discharged more often to nursing care facilities (17% versus 5%; P=0.003). In logistic regression models there were no differences in odds ratio for favorable or poor outcome, other than tendency for higher in-hospital mortality in elderly patients (odds ratio, 2.8; 95% CI, 0.81 to 9.62; P=0.10). CONCLUSIONS Among AIS patients treated with intravenous tPA, age-related differences in characteristics and disposition were identified. No evidence for withholding tPA treatment for AIS in appropriately selected patients aged >/=80 years was identified.

The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke The CLEAR Stroke Trial

Background and Purpose— Multiple approaches are being studied to enhance the rate of thrombolysis for acute ischemic stroke. Treatment of myocardial infarction with a combination of a reduced-dose fibrinolytic agent and a glycoprotein (GP) IIb/IIIa receptor antagonist has been shown to improve the rate of recanalization versus fibrinolysis alone. The combined approach to lysis utilizing eptifibatide and recombinant tissue-type plasminogen activator (rt-PA) (CLEAR) stroke trial assessed the safety of treating acute ischemic stroke patients within 3 hours of symptom onset with this combination. Methods— The CLEAR trial was a National Institutes of Health/National Institute of Neurological Disorders and Stroke–funded multicenter, double-blind, randomized, dose-escalation and safety study. Patients were randomized 3:1 to either low-dose rt-PA (tier 1=0.3 mg/kg, tier 2=0.45 mg/kg) plus eptifibatide (75 &mgr;g/kg bolus followed by 0.75 &mgr;g/kg per min infusion for 2 hours) or standard-dose rt-PA (0.9 mg/kg). The primary safety end point was the incidence of symptomatic intracerebral hemorrhage within 36 hours. Secondary analyses were performed regarding clinical efficacy. Results— Ninety-four patients (40 in tier 1 and 54 in tier 2) were enrolled. The combination group of the 2 dose tiers (n=69) had a median age of 71 years and a median baseline National Institutes of Health Stroke Scale (NIHSS) score of 14, and the standard-dose rt-PA group (n=25) had a median age of 61 years and a median baseline NIHSS score of 10 (P=0.01 for NIHSS score). Fifty-two (75%) of the combination treatment group and 24 (96%) of the standard treatment group had a baseline modified Rankin scale score of 0 (P=0.04). There was 1 (1.4%; 95% CI, 0% to 4.3%) symptomatic intracranial hemorrhage in the combination group and 2 (8.0%; 95% CI, 0% to 19.2%) in the rt-PA–only arm (P=0.17). During randomization in tier 2, a review by the independent data safety monitoring board demonstrated that the safety profile of combination therapy at the tier 2 doses was such that further enrollment was statistically unlikely to indicate inadequate safety for the combination treatment group, the ultimate outcome of the study. Thus, the study was halted. There was a trend toward increased clinical efficacy of standard-dose rt-PA compared with the combination treatment group. Conclusions— The safety of the combination of reduced-dose rt-PA plus eptifibatide justifies further dose-ranging trials in acute ischemic stroke.

Number Needed to Treat to Benefit and to Harm for Intravenous Tissue Plasminogen Activator Therapy in the 3- to 4.5-Hour Window. Joint Outcome Table Analysis of the ECASS 3 Trial

Background and Purpose— Measures of a therapy’s effect size are important guides to clinicians, patients, and policy-makers on treatment decisions in clinical practice. The ECASS 3 trial demonstrated a statistically significant benefit of intravenous tissue plasminogen activator for acute cerebral ischemia in the 3- to 4.5-hour window, but an effect size estimate incorporating benefit and harm across all levels of poststroke disability has not previously been derived. Methods— Joint outcome table specification was used to derive number needed to treat to benefit (NNTB) and number needed to treat to harm (NNTH) values summarizing treatment impact over the entire outcome range on the modified Rankin scale of global disability, including both expert-dependent and expert-independent (algorithmic and repeated random sampling) array generation. Results— For the full 7-category modified Rankin scale, algorithmic analysis demonstrated that the NNTB for 1 additional patient to have a better outcome by ≥1 grades than with placebo must lie between 4.0 and 13.0. In bootstrap simulations, the mean NNTB was 7.1. Expert joint outcome table analyses indicated that the NNTB for improved final outcome was 6.1 (95% CI, 5.6–6.7) and the NNTH 37.5 (95% CI, 34.6–40.5). Benefit per 100 patients treated was 16.3 and harm per 100 was 2.7. The likelihood of help to harm ratio was 6.0. Conclusions— Treatment with tissue plasminogen activator in the 3- to 4.5-hour window confers benefit on approximately half as many patients as treatment <3 hours, with no increase in the conferral of harm. Approximately 1 in 6 patients has a better and 1 in 35 has a worse outcome as a result of therapy.

Cost-effectiveness of helicopter transport of stroke patients for thrombolysis

OBJECTIVES Treatment with intravenous (IV) or intra-arterial (IA) thrombolysis in patients with acute ischemic stroke demands careful patient selection and specialized institutional capabilities. Physicians at hospitals without these resources may prefer patient transfer for acute treatment. Helicopter transport for these patients has been described but without analysis of the effects of its additional cost. The authors examined the cost-effectiveness of helicopter transport for patients with acute stroke. METHODS Costs per additional good outcome and per quality-adjusted life-year (QALY) were calculated using a computer model. Input variables included flight, thrombolytic agent, and angiography costs; annual cost per patient for long-term care of symptomatic stroke; percentage of transported patients treated; percentage of patients receiving IV versus IA therapy; discount rate; absolute probability of good outcome; annual mortality with and without treatment; and quality-of-life modifier. Sensitivity analysis was performed. RESULTS Helicopter transport of acute stroke patients to tertiary care centers for thrombolytic therapy costs

Recovery of Cognitive Function After Surgery for Aneurysmal Subarachnoid Hemorrhage

35,000 per additional good outcome and

Analysis of Canadian Population With Potential Geographic Access to Intravenous Thrombolysis for Acute Ischemic Stroke

3,700 per QALY for the reference case. Cost-effectiveness was sensitive to the effectiveness of thrombolysis but minimally sensitive to most other input values. Cost per QALY ranged from

Prevalence of Atrial Fibrillation and Antithrombotic Prophylaxis in Emergency Department Patients

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