Cost-Effectiveness of Project ADAM

Public access defibrillation (PAD) in the adult population is thought to be both efficacious and cost-effective. Similar programs aimed at children and adolescents have not been evaluated for their cost-effectiveness. This study evaluates the potential cost-effectiveness of implementing Project ADAM, a program targeting children and adolescents in high schools in the Milwaukee Public School System. Project ADAM provides education about cardiopulmonary resuscitation (CPR) and the warning signs of sudden cardiac death (SCD) and training in the use and placement of automated external defibrillators (AEDs) in high schools. We developed decision analysis models to evaluate the cost-effectiveness of the decision to implement Project ADAM in public high schools in Milwaukee. We examined clinical model and public policy applications. Data on costs included estimates of hospital-based charges derived from a pediatric medical center where a series of patients were treated for SCD, educational programming, and the direct costs of one AED and training for 15 personnel per school. We performed sensitivity analyses to assess the variation in outputs with respect to changes to input data. The main outcome measures were Life years saved and incremental cost-effectiveness ratios. At an arbitrary societal willingness to pay $100,000 per life year saved, the policy to implement Project ADAM in schools is a cost-effective strategy at a threshold of approximately 5 patients over 5 years for the clinical model and approximately 8 patients over 5 years for the public policy model. Implementation of Project ADAM in high schools in the United States is potentially associated with an incremental cost-effectiveness ratio that is favorable.     

Radiology-Pathology Conference: Bilateral renal oncocytomas

Oncocytoma is an uncommon benign, typically solitary renal tumor first reported in 1942. Renal oncocytomas are rarely multiple and/or bilateral. Accurate preoperative diagnosis and differentiation from renal carcinoma is difficult. We report the radiology and pathology of a patient with bilateral renal oncocytomas and review the literature of this rare presentation.     

Human sympathetic activation by alpha2-adrenergic blockade with yohimbine: Bimodal, epistatic influence of cytochrome P450-mediated drug metabolism

BACKGROUND: alpha2-Adrenergic blockade responses suggest adrenergic dysfunction in hypertension. alpha2-Blockade is also used to treat autonomic dysfunction. However, pharmacokinetic determinants of yohimbine disposition are not understood. METHODS: We evaluated alpha2-blockade with intravenous yohimbine in 172 individuals. Specific cytochrome P450 (CYP) isoform-mediated metabolism was investigated. Results were evaluated by ANOVA and by maximum likelihood analysis for bimodality of response distributions. RESULTS: Yohimbine metabolism to 11-hydroxy-yohimbine displayed greater than 1000-fold variability, with 17 individuals showing no metabolism. Nonmetabolizers differed from others in ethnicity but not in age, sex, body habitus, blood pressure, heart rate, or family history of hypertension. Bimodality of metabolism was suggested by frequency histogram, as well as maximum likelihood and cluster analysis. Among ethnic groups, subjects of European ancestry had the highest frequency of nonmetabolism. In vitro oxidation suggested that the major route of metabolism (lowest Michaelis-Menten constant and greatest intrinsic clearance) was likely via CYP2D6 to 11-hydroxy-yohimbine. In vivo genotypes at both CYP2D6 and CYP3A4 were necessary to predict metabolism (overall F = 3.03, P =.005); an interaction of alleles at these 2 loci (interaction F = 3.05, P =.033) suggested an epistatic effect on drug metabolism in vivo. Nonmetabolizers had greater activation of sympathetic nervous system activity. Yohimbine increased blood pressure, an effect mediated hemodynamically by elevation of cardiac output rather than systemic vascular resistance. Blood pressure and cardiac output responses did not differ by metabolizer group. CONCLUSIONS: We conclude that heterogeneous, bimodally distributed yohimbine metabolism depends on common genetic variation in both CYP2D6 and CYP3A4 and contributes to differences in sympathetic neuronal response to alpha2-blockade. These results have implications for both diagnostic and therapeutic uses of this alpha2-antagonist.     

Effectiveness of a multidisciplinary quality improvement initiative in reducing door-to-balloon times in primary angioplasty

Primary angioplasty (PA) for acute myocardial infarction (AMI) has emerged as the standard of care in hospitals with cardiac interventional facilities. The benefits from the PA are time dependent, but recent data raise concerns regarding the timeliness of delivery of care in AMI and the level of benefit achieved by current standards. We assessed the effectiveness of an extensive multidisciplinary quality improvement initiative in reducing door-to-balloon (DTB) times in PA. The PA process was divided into six separate time periods, which were assessed individually. Subsequent quality initiatives resulted in a dramatic reduction in the mean DTB time (141.3 minutes preintervention compared to 95.1 minutes postintervention; P < 0.001).