Adjunctive Intravenous Argatroban or Eptifibatide for Ischemic Stroke.

Background: Intravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear.

Methods: We conducted a phase 3, three-group, adaptive, single-blind, randomized, controlled clinical trial at 57 sites in the United States.

Impact of individual clinical outcomes on trial participants' perspectives on enrollment in emergency research without consent.

Background: Evidence suggests that patients are generally accepting of their enrollment in trials for emergency care conducted under exception from informed consent. It is unknown whether individuals with more severe initial injuries or worse clinical outcomes have different perspectives. Determining whether these differences exist may help to structure post-enrollment interactions.

A Novel Approach to the Treatment of Orolingual Angioedema After Tissue Plasminogen Activator Administration.

Orolingual angioedema is a rare adverse effect of tissue plasminogen activator (tPA), with an incidence of 1% to 5%. There are currently no published reports describing resolution of tPA-induced orolingual angioedema with complement inhibitor therapy. A 72-year-old man receiving home angiotensin-converting enzyme inhibitor therapy presented to the emergency department with newly developed orolingual angioedema after treatment with tPA for acute ischemic stroke.

Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue-Type Plasminogen Activator in Acute Ischemic Stroke-Full Dose Regimen Stroke Trial.

Background And Purpose: The Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue-Type Plasminogen Activator (r-tPA; CLEAR) in Acute Ischemic Stroke (AIS) and CLEAR-Enhanced Regimen (CLEAR-ER) trials demonstrated safety of reduced dose r-tPA plus the glycoprotein 2b/3a inhibitor, eptifibatide, in AIS compared with r-tPA alone. The objective of the CLEAR-Full Dose Regimen (CLEAR-FDR) trial was to estimate the rate of symptomatic intracerebral hemorrhage (sICH) in AIS patients treated with the combination of full-dose r-tPA plus eptifibatide.

Methods: CLEAR-FDR was a single-arm, prospective, open-label, multisite study.

Patients' perspectives of enrollment in research without consent: the patients' experiences in emergency research-progesterone for the treatment of traumatic brain injury study.

Objective: Research in acute illness often requires an exception from informed consent. Few studies have assessed the views of patients enrolled in exception from informed consent trials. This study was designed to assess the views of patients and their surrogates of exception from informed consent enrollment within the context of a randomized, placebo-controlled trial of an investigational agent for traumatic brain injury.

Recombinant tissue-type plasminogen activator plus eptifibatide versus recombinant tissue-type plasminogen activator alone in acute ischemic stroke: propensity score-matched post hoc analysis.

Background And Purpose: The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke-Enhanced Regimen (CLEAR-ER) trial demonstrated safety of recombinant tissue-type plasminogen activator (r-tPA) plus eptifibatide in acute ischemic stroke (AIS). CLEAR-ER randomized AIS patients (5:1) to 0.6 mg/kg r-tPA plus eptifibatide versus standard r-tPA (0.

Gene expression in peripheral immune cells following cardioembolic stroke is sexually dimorphic.

Aims: Epidemiological studies suggest that sex has a role in the pathogenesis of cardioembolic stroke. Since stroke is a vascular disease, identifying sexually dimorphic gene expression changes in blood leukocytes can inform on sex-specific risk factors, response and outcome biology. We aimed to examine the sexually dimorphic immune response following cardioembolic stroke by studying the differential gene expression in peripheral white blood cells.

ED disposition of the Glasgow Coma Scale 13 to 15 traumatic brain injury patient: analysis of the Transforming Research and Clinical Knowledge in TBI study.

Objective: Mild traumatic brain injury (mTBI) patients are frequently admitted to high levels of care despite limited evidence suggesting benefit. Such decisions may contribute to the significant cost of caring for mTBI patients. Understanding the factors that drive disposition decision making and how disposition is associated with outcomes is necessary for developing an evidence-base supporting disposition decisions.

A matched comparison of eptifibatide plus rt-PA versus rt-PA alone in acute ischemic stroke.

Background: The Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue Plasminogen Activator (rt-PA) in Acute Ischemic Stroke-Enhanced Regimen (CLEAR-ER) trial found that intravenous rt-PA plus eptifibatide (combination arm) in acute ischemic stroke (AIS) was safe and had a direction of effect that would justify a phase III trial. CLEAR-ER had unanticipated imbalances between treatment groups. We compared the rates of symptomatic intracranial hemorrhage (sICH) and good outcomes for combination therapy patients in the CLEAR-ER trial to a matched cohort of rt-PA patients from the National Institute of Neurological Disorders and Stroke (NINDS) trial.

Combined approach to lysis utilizing eptifibatide and recombinant tissue plasminogen activator in acute ischemic stroke-enhanced regimen stroke trial.

Background And Purpose: In a previous study, 0.3 and 0.45 mg/kg of intravenous recombinant tissue plasminogen activator (rt-PA) were safe when combined with eptifibatide 75 mcg/kg bolus and a 2-hour infusion (0.

Enrollment in research under exception from informed consent: the Patients' Experiences in Emergency Research (PEER) study.

Background: Resuscitation research requires an exception from informed consent (EFIC). Despite concerns that patients may find EFIC unacceptable, the views and experiences of patients enrolled in an EFIC study are largely unknown.

Methods: The Patients' Experience in Emergency Research (PEER) study was nested within the Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) for pre-hospital treatment of status epilepticus.

RNA in blood is altered prior to hemorrhagic transformation in ischemic stroke.

Objective: Hemorrhagic transformation (HT) is a major complication of ischemic stroke that worsens outcomes and increases mortality. Disruption of the blood-brain barrier is a central feature of HT pathogenesis, and leukocytes may contribute to this process. We sought to determine whether ischemic strokes that develop HT have differences in RNA expression in blood within 3 hours of stroke onset prior to treatment with thrombolytic therapy.

Y chromosome gene expression in the blood of male patients with ischemic stroke compared with male controls.

Background: Sex is suggested to be an important determinant of ischemic stroke risk factors, etiology, and outcome. However, the basis for this remains unclear. The Y chromosome is unique in males.

Intramuscular versus intravenous therapy for prehospital status epilepticus.

Background: Early termination of prolonged seizures with intravenous administration of benzodiazepines improves outcomes. For faster and more reliable administration, paramedics increasingly use an intramuscular route.

Methods: This double-blind, randomized, noninferiority trial compared the efficacy of intramuscular midazolam with that of intravenous lorazepam for children and adults in status epilepticus treated by paramedics.

Effects of gender on gene expression in the blood of ischemic stroke patients.

This study examined the effects of gender on RNA expression after ischemic stroke (IS). RNA obtained from blood of IS patients (n=51; 153 samples at < or =3, 5, and 24 hours) and from matched controls (n=52) were processed on Affymetrix microarrays. Analyses of covariance for stroke versus control samples were performed separately for both genders and the regulated genes for females compared with males.

The X-chromosome has a different pattern of gene expression in women compared with men with ischemic stroke.

Background And Purpose: Differences in ischemic stroke between men and women have been mainly attributed to hormonal effects. However, sex differences in immune response to ischemia may exist. We hypothesized that differential expression of X-chromosome genes in blood immune cells contribute to differences between men and women with ischemic stroke.

Efficiency of enrollment in a successful phase II acute stroke clinical trial.

Background: Recruitment challenges are common in acute stroke clinical trials. In a population-based study, we determined eligibility and actual enrollment for a successful, phase II acute stroke clinical trial. We hypothesized that missed opportunities for enrollment of eligible patients occurred frequently, despite the success of the trial.

Inter-hospital communications and transport: turning one-way funnels into two-way networks.

The Inter-hospital Communications and Transport workgroup was charged with exploring the current status, barriers, and data necessary to optimize the initial destination and subsequent transfer of patients between and among acute care settings. The subtitle, "Turning Funnels Into Two-way Networks," is descriptive of the approach that the workgroup took by exploring how and when smaller facilities in suburban, rural, and frontier areas can contribute to the daily business of caring for emergency patients across the lower-acuity spectrum-in some instances with consultant support from academic medical centers. It also focused on the need to identify high-acuity patients and expedite triage and transfer of those patients to facilities with specialty resources.

Signatures of cardioembolic and large-vessel ischemic stroke.

Objective: The cause of stroke remains unknown or cryptogenic in many patients. We sought to determine whether gene expression signatures in blood can distinguish between cardioembolic and large-vessel causes of stroke, and whether these profiles can predict stroke etiology in the cryptogenic group.

Methods: A total of 194 samples from 76 acute ischemic stroke patients were analyzed.

Making the right choice: optimizing rt-PA and eptifibatide lysis, an in vitro study.

Introduction: Recombinant tissue plasminogen activator (rt-PA) is the only FDA approved lytic therapy for acute ischemic stroke. However, there can be complications such as intra-cerebral hemorrhage. This has led to interest in adjuncts such as GP IIb-IIIa inhibitors.

Gene expression profiling of blood for the prediction of ischemic stroke.

Background And Purpose: A blood-based biomarker of acute ischemic stroke would be of significant value in clinical practice. This study aimed to (1) replicate in a larger cohort our previous study using gene expression profiling to predict ischemic stroke; and (2) refine prediction of ischemic stroke by including control groups relevant to ischemic stroke.

Methods: Patients with ischemic stroke (n=70, 199 samples) were compared with control subjects who were healthy (n=38), had vascular risk factors (n=52), and who had myocardial infarction (n=17).

Midazolam versus diazepam for the treatment of status epilepticus in children and young adults: a meta-analysis.

Background: Rapid treatment of status epilepticus (SE) is associated with better outcomes. Diazepam and midazolam are commonly used, but the optimal agent and administration route is unclear.

Objectives: The objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam, by any route, in terminating SE seizures in children and adults.

Time-critical neurological emergencies: the unfulfilled role for point-of-care testing.

Background: Neurological emergencies are common and frequently devastating. Every year, millions of Americans suffer an acute stroke, severe traumatic brain injury, subarachnoid hemorrhage, status epilepticus, or spinal cord injury severe enough to require medical intervention.

Aims: Full evaluation of the diseases in the acute setting often requires advanced diagnostics, and treatment frequently necessitates transfer to specialized centers.

Ancrod in acute ischemic stroke: results of 500 subjects beginning treatment within 6 hours of stroke onset in the ancrod stroke program.

Background And Purpose: Previous studies of multiple-day dosing with the defibrinogenating agent, ancrod, in acute ischemic stroke yielded conflicting results but suggested that a brief dosing regimen might improve efficacy and safety. The Ancrod Stroke Program was designed to test this concept in subjects beginning ancrod or placebo within 6 hours of the onset of acute ischemic stroke.

Methods: Five hundred subjects with acute ischemic stroke who could begin receiving study material within 6 hours of symptom onset were infused intravenously with either ancrod (0.

Do either corticosteroids or antiviral agents reduce the risk of long-term facial paresis in patients with new-onset Bell's palsy?

Background: The cause of Bell's palsy remains uncertain, although accumulating evidence suggests a viral etiology. To date, treatment to minimize long-term deficits from this disorder typically includes anti-inflammatory or antiviral medication.

Clinical Question: Do corticosteroids or antiviral agents, either alone or in combination, reduce the risk of long-term facial paresis in patients with new-onset Bell's palsy?

Evidence Review: Three multicenter, randomized, controlled trials enrolled over 1,500 adult patients with paroxysmal, unilateral paresis of cranial nerve VII and treated them with varying regimens and combinations of prednisolone, antiviral agents, and placebo, and evaluated complete recovery up to 12 months later.