Richard S. Mackenzie

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.

Analysis of sex differences in preadmission management of ST-segment elevation (STEMI) myocardial infarction.

BACKGROUND Many reports suggest gender disparity in cardiac care as a contributor to the increased mortality among women with heart disease. OBJECTIVE We sought to identify gender differences in the management of Myocardial Infarction (MI) Alert-activated ST-segment elevation myocardial infarction (STEMI) patients that may have resulted from prehospital initiation. METHODS A retrospective database was created for MI Alert STEMI patients who presented to the emergency department (ED) of an academic community hospital with 74,000 annual visits from April 2000 through December 2008. Included were patients meeting criteria for an MI Alert (an institutional clinical practice guideline designed to expedite cardiac catheterization for STEMI patients). Data points (before and after initiation of a prehospital alert protocol) were compared and used as markers of therapy: time to ECG, receiving β-blockers, and time to the catheterization laboratory (cath lab). Differences in categorical variables by patient sex were assessed using the χ(2) test. Medians were estimated as the measure of central tendency. Quantile regression models were used to assess differences in median times between subgroups. RESULTS A total of 1231 MI Alert charts were identified and analyzed. The majority of the study population were male (70%), arrived at the ED via ambulance (60.1%), and were taking a β-blocker (67.8%) or aspirin (91.6%) at the time of the ED admission. Female patients were more likely than male patients to arrive at the ED via ambulance (65.9% vs 57.6%, respectively; P = 0.014). The median age of female patients was 68 years, whereas male patients were significantly younger (median age, 59 years; P < 0.001). The proportion of patients currently taking a β-blocker or low-dose aspirin did not vary by gender. Overall, 78.2% of the MI Alert patients arriving at the ED were MI2 (alert initiated by ED physician), and this did not vary by gender (P = 0.33). A total of 1064 MI Alert patients went to the cath lab: 766 male patients (88.9%) and 298 female patients (80.8%). Overall, the median time to cath lab arrival was 79 minutes for men and 81 minutes for women (P = 0.38). Overall, the median time to cath lab arrival significantly decreased from MI1 to MI3, (P(trend) < 0.001). For prehospital-initiated alerts (MI3), the median time to cath lab arrival was the same for men and women (64 minutes; P = 1.0). For hospital-initiated alerts, time to cath lab arrival was 82 minutes for male patients and 84 minutes for female patients (P = 0.38). Prehospital activation of the process decreased the time to the cath lab by 19 minutes (P < 0.001; 95% CI, 13.2-24.8). CONCLUSION No significant gender differences were apparent in the STEMI patients analyzed, whether the MI Alert was initiated in the ED or prehospital initiated. Initiating prehospital-based alerts significantly decreased the time to the cath lab.

Gender Differences in Neurologic Emergencies Part I: A Consensus Summary and Research Agenda on Cerebrovascular Disease

Cerebrovascular neurologic emergencies including ischemic and hemorrhagic stroke, subarachnoid hemorrhage (SAH), and migraine are leading causes of death and disability that are frequently diagnosed and treated in the emergency department (ED). Although sex and gender differences in neurologic emergencies are beginning to become clearer, there are many unanswered questions about how emergency physicians should incorporate sex and gender into their research initiatives, patient evaluations, and overall management plans for these conditions. After evaluating the existing gaps in the literature, a core group of ED researchers developed a draft of future research priorities. Participants in the 2014 Academic Emergency Medicine consensus conference neurologic emergencies working group then discussed and approved the recommended research agenda using a standardized nominal group technique. Recommendations for future research on the role of sex and gender in the diagnosis, treatment, and outcomes pertinent to ED providers are described for each of three diagnoses: stroke, SAH, and migraine. Recommended future research also includes investigation of the biologic and pathophysiologic differences between men and women with neurologic emergencies as they pertain to ED diagnoses and treatments.

Gender Disparity in Emergency Department Non-ST Elevation Myocardial Infarction Management

BACKGROUND Many studies have looked at differences between men and women with acute coronary syndrome. These studies demonstrate that women have worse outcomes, receive fewer invasive interventions, and experience delay in the initiation of established medical therapies. OBJECTIVE Using innovative technology, we set out to unveil and resolve any gender disparities in the evaluation and treatment of patients presenting with a positive troponin while in the emergency department. Our goal was to assess the feasibility of using a business management query system to create an automated data report that could identify deficiencies in standards of care and be used to improve the quality of treatment we provide our patients. METHODS Over a 12-month period, key markers for patients with non-ST elevation myocardial infarction (NSTEMI) were tracked (e.g., time to electrocardiogram, door to medications). During this time, educational endeavors were initiated utilizing McKessons Horizon Business Insight™ (McKesson Information Solutions, Alpharetta, GA) to illustrate gender differences in standard therapy. Subsequently, indicators were evaluated for improvement. RESULTS Substantial improvements in key indicators for management of NSTEMI were obtained and gender differences minimized where education was provided. CONCLUSION The integration of these information systems allowed us to create a successful performance improvement tool and, as an added benefit, nearly eliminated the need for manual retrospective chart reviews.

Computer-Based Reminder System Effectively Impacts Physician Documentation

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Achieving succession planning and implementation: One healthcare network's story

Frequent transitions in leadership can cause inefficiency, inconsistency, and lack of alignment with priorities and strategy. Retaining management talent and collaboratively planning their succession can help ensure organizational survival. Succession planning, in healthcare and other industries, addresses some of these concerns; however, there is a dearth of descriptive articles emphasizing “how to.” This article demonstrates one healthcare networks comprehensive system for succession planning and implementation. Leaders looking to plan their human resource processes for organizational sustainability would be able to emulate and adapt practices for their networks.

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

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.

Triple setup airway—simultaneous oropharyngeal, surgical, and ECMO preparation

Extracorporeal membrane oxygenation is increasingly used in the intensive care unit for refractory cardiopulmonary diseases [1]. There has been little application at this time of its use in the emergency department (ED) and none for its use in high-risk airways. We present a case of a patient with supraglottitis and large parapharyngeal abscesses causing an unstable airway that would be difficult to manage with traditional “double setup” (oropharyngeal and surgical) methodology. We highlight the potential use of extracorporeal membrane oxygenation in the management of her airway. Extracorporeal membrane oxygenation (ECMO) is used in intensive care medicine for treating refractory cardiopulmonary diseases. While traditionally, ECMO has been used to support patients suffering from ARDS, there has been increased interest in exploring the use of EMO for various diseases [1,2]. For instance, the use of ECMO as a bridge to treatment and recovery in cardiac arrest has been studied [1,3,4]. Additionally, reports have appeared in the literature concerning the use of ECMO in severe accidental hypothermia [5,6]. There are few documented reports of ECMObeing used for difficult airways and none specifically in the ED [7–9]. We report a case of ECMO as a management option in the ED for a woman with extensive parapharyngeal abscesses. A 58-year-old woman with a history of GERD presented to the ED complaining of throat pain. She had previously been seen at an urgent care facility three days prior, and diagnosed with viral pharyngitis. Her symptoms worsened, which prompted her ED visit. On arrival, she complained of fevers, chest tightness, neck swelling and dysphagia. Initial vitals included blood pressure, 106/58 mmHg; pulse, 77 beats/minute; temperature, 96.7°F; respirations, 14; and oxygen saturation, 100%. The patient was awake and alert. She had mild pharyngeal erythema, a midline uvula and no obvious peritonsillar swelling or abscess. Remarkable blood chemistries measured: WBCs, 19.2 (4-10.0 thou/cmm) with left shift; and creatinine, 1.32 (0.53-1.20 mg/dL). A CT of the patients neck with contrast showed extensive supraglottic edema with narrowing of the airway at the level of the false vocal cords (Figs. 1,2). In addition, there were multiple abscesses in the neck with extension into the retropharynx and mediastinum. She was treated with broad-spectrum antibiotics and steroids. Definitive surgical care was anticipated to be difficult. While the patient was not in acute airway obstruction at that time, the rapid progression of this disease raised the possibility of an imminent airway collapse. ☆ The authors have no outside support information, conflicts or financial interest to

Using Medical Student Quality Improvement Projects to Promote Evidence-Based Care in the Emergency Department

Introduction The Association of American Medical Colleges’ (AAMC) initiative for Core Entrustable Professional Activities for Entering Residency includes as an element of Entrustable Professional Activity 13 to “identify system failures and contribute to a culture of safety and improvement.” We set out to determine the feasibility of using medical students’ action learning projects (ALPs) to expedite implementation of evidence-based pathways for three common patient diagnoses in the emergency department (ED) setting (Atrial fibrillation, congestive heart failure, and pulmonary embolism). Methods These prospective quality improvement (QI) initiatives were performed over six months in three Northeastern PA hospitals. Emergency physician mentors were recruited to facilitate a QI experience for third-year medical students for each project. Six students were assigned to each mentor and given class time and network infrastructure support (information technology, consultant experts in lean management) to work on their projects. Students had access to background network data that revealed potential for improvement in disposition (home) for patients. Results Under the leadership of their mentors, students accomplished standard QI processes such as performing the background literature search and assessing key stakeholders’ positions that were involved in the respective patient’s care. Students effectively developed flow diagrams, computer aids for clinicians and educational programs, and participated in recruiting champions for the new practice standard. They met with other departmental clinicians to determine barriers to implementation and used this feedback to help set specific parameters to make clinicians more comfortable with the changes in practice that were recommended. All three clinical practice guidelines were initiated at consummation of the students’ projects. After implementation, 86% (38/44) of queried ED providers felt comfortable with medical students being a part of future ED QI initiatives, and 84% (26/31) of the providers who recalled communicating with students on these projects felt they were effective. Conclusion Using this novel technique of aligning small groups of medical students with seasoned mentors, it is feasible for medical students to learn important aspects of QI implementation and allows for their engagement to more efficiently move evidence-based medicine from the literature to the bedside.

The C ombined Approach to L ysis Utilizing E ptifibatide a nd r t-PA in Acute Ischemic Stroke

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.