Faculty Bibliography

Stroke is a major public health issue, and stroke recurrence accounts for a quarter of all events. Antiplatelet therapy has been extensively studied for secondary stroke prevention and is established as effective in this high-risk population. Several agents have been evaluated in this setting, both in isolation and combination. The most widely used antiplatelet medications are aspirin, clopidogrel, and aspirin plus extended-release dipyridamole. However, new agents and combinations continue to be evaluated. A detailed review of the evidence supporting various antiplatelet regimens for secondary stroke prevention is outlined with special focus on recent developments that may impact clinical management of patients with stroke or TIA.

BACKGROUND AND PURPOSE: Hemodialysis patients are at high risk for ischemic stroke, and previous studies have noted a high rate of cardioembolism in this population. The aim of this study was to determine ischemic stroke causes among hemodialysis patients and elucidate specific cardioembolic stroke mechanisms. METHODS: This study is a retrospective cross-sectional study of hemodialysis patients admitted with acute stroke to the University of Pennsylvania Health System between 2003 and 2010. Strokes were classified using modified Trial of Org 10,172 in Acute Stroke Treatment (TOAST) criteria as large vessel, cardioembolism, small vessel, atypical, multiple causes, or cryptogenic. Cardioembolic strokes were further characterized for specific mechanism. RESULTS: We identified 52 patients hospitalized with acute stroke while receiving hemodialysis. Mean age was 64+/-13 years, 56% were female, and 67% were black. Stroke subtypes included 3 (6%) large vessel, 20 (38%) cardioembolism, 6 (11%) small vessel, 3 (6%) other, 4 (8%) with multiple causes, and 16 (31%) were unknown. Among patients who had an echocardiogram performed, 5 of 52 (10%; 95% confidence interval, 1%-18%) had a patent foramen ovale. Cardioembolic stroke mechanisms included 6 with infective endocarditis (accounting for 12% of all strokes). CONCLUSIONS: Cardioembolism and cryptogenic stroke are the predominant stroke mechanisms among hemodialysis patients. Infective endocarditis was identified frequently relative to other stroke cohorts, and a raised index of suspicion is warranted in the hemodialysis population.

OPINION STATEMENT: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme involved in the metabolism of Low-density lipoprotein (LDL) to pro-inflammatory mediators. Lp-PLA2 is highly expressed in the necrotic core of atherosclerotic plaques and has been associated with atherosclerotic plaque instability. Multiple studies have shown an association between elevated Lp-PLA2 levels and risk of both stroke and myocardial infarction, even after adjustment for standard vascular risk factors, and several professional organizations have recommended Lp-PLA2 as a potentially usefully tool to improve risk stratification for individual patients. Therapies directed at lowering Lp-PLA2 levels may represent a novel approach to reducing vascular risk, though direct clinical benefit from targeting treatment to Lp-PLA2 levels remains unproven. Statins appear to significantly lower Lp-PLA2 levels; fibrates and niacin may also lower Lp-PLA2 levels, though this is less well established. Darapladib, a potent, selective Lp-PLA2 inhibitor, is currently in phase III trials for prevention of recurrent vascular events in patients with coronary artery disease.

BACKGROUND AND PURPOSE: The ABCD(2) score is increasingly used for risk stratification of transient ischemic attack patients. We sought to determine the reliability and convergent validity of retrospective ABCD(2) score estimation from medical records. METHODS: We compared ABCD(2) scores that were prospectively determined by a vascular neurology attending to scores determined retrospectively from medical record review. Emergency department records and neurology consult notes for patients with acute transient ischemic attack were abstracted with explicit ABCD(2) scoring redacted. Scores were estimated by 2 independent raters using these records. Estimated ABCD(2) component scores, total scores, and risk category were compared both between retrospective raters and with prospectively obtained scores. Reliability was assessed using unweighted kappa statistics. RESULTS: Interrater reliability was substantial with 72% exact agreement in total score between retrospective raters (kappa=0.64) and nearly perfect with 82% agreement for ABCD(2) category (kappa=0.71). Interrater agreement was best for age and diabetes mellitus and poorest for clinical features and duration. Agreement between the retrospective raters and prospectively obtained score was >90% for age, blood pressure, and diabetes mellitus, but only approximately 70% for clinical features and duration. Retrospectively, estimated total ABCD(2) score exactly matched the prospective score in 58% of patients for rater 1 and 44% of patients for rater 2. Retrospectively, estimated ABCD(2) category matched the prospectively scored category in 67% of patients for rater 1 and 71% of patients for rater 2. CONCLUSIONS: The ABCD(2) score can be abstracted from medical records with substantial interrater reliability but limited convergent validity. This may lead to misclassification of risk category in more than one third of patients.

BACKGROUND: Improving handoff communications is a National Patient Safety Goal. Interns and residents are rarely taught how to safely handoff their patients. Our objective was to determine whether teaching safe handoff principles would improve handoff quality. METHODS: Our study was conducted on the inpatient services at 2 teaching hospitals. In this single-institution, randomized controlled trial, internal medicine interns (N = 44) and residents (N = 24) participated in a 45-minute educational session on safe handoff communication skills. Residents received additional education on effective feedback practices and were asked to provide each intern with structured feedback. Quality of interns' electronic and verbal handoffs was measured by using a Handoff Evaluation Tool created by the authors. The frequency of handoff communication failures was also assessed through semistructured phone interviews of postcall interns. RESULTS: Interns who received handoff education demonstrated superior verbal handoff skills than control interns (P < .001), while no difference was seen in electronic handoff skills. Communication failures related to code status (P < .001) and overnight tasks (P < .050) were less frequent in the intervention group. CONCLUSIONS: Interns' electronic handoff documentation skills did not improve with the intervention. This may reflect greater difficulty in changing physicians' electronic documentation habits.

A 70-year-old woman with a history of undifferentiated connective tissue disease was admitted for work-up of shortness of breath and progressive weakness over the course of 1 year. She had been treated with hydroxychloroquine (HCQ) for last 5 years. Her evaluation revealed diffuse muscle weakness and hyperpigmentation of the skin consistent with HCQ deposition, although this did not entirely explain the patient's dyspnea. The patient underwent cardiac evaluation because of occasional substernal chest pain and persistent elevation in serum troponin I, but her ECG and adenosine thallium study did not show any signs of ischemic heart disease. The diagnosis of HCQ-induced myopathy was made with electromyography and muscle biopsy. HCQ was discontinued, with improvement of the patient's signs and symptoms over the course of the next 18 months.We propose that this patient was experiencing myocardial toxicity as a consequence of HCQ deposition disease with her clinical picture of skeletal muscle myopathy and HCQ deposition in the skin. A Medline search yielded several case reports as well as a case series of patients with antimalarial-induced myopathy. HCQ-induced myopathy may be less recognized because of its presentation with signs, symptoms, and laboratory results which suggest other critical diseases. Moreover, this medication is often prescribed to treat illnesses whose clinical manifestations may include myopathy.