Coronary artery disease (CAD) with associated myocardial infarction (MI) is the most common cause of morbidity and mortality in the United States.¹ Often MI is the first symptom of CAD, suggesting the need for more effective screening of high-risk, asymptomatic patients.^1,2

Background—: Warfarin is characterized by marked variations in individual dose requirements and a narrow therapeutic window. Pharmacogenetics (PG) could improve dosing efficiency and safety, but clinical trials evidence is meager. Methods and Results—: A Randomized and Clinical Effectiveness Trial Comparing Two Pharmacogenetic Algorithms and Standard Care for Individualizing Warfarin Dosing (CoumaGen-II) comprised 2 comparisons: (1) a blinded, randomized comparison of a modified 1-step (PG-1) with a 3-step algorithm (PG-2) (N=504), and (2) a clinical effectiveness comparison of PG guidance with use of either algorithm with standard dosing in a parallel control group (N=1866). A rapid method provided same-day CYP2C9 and VKORC1 genotyping. Primary outcomes were percentage of out-of-range international normalized ratios at 1 and 3 months and percentage of time in therapeutic range. Primary analysis was modified intention to treat. In the randomized comparison, PG-2 was noninferior but not superior to PG-1 for percentage of out-of-range international normalized ratios at 1 month and 3 months and for percentage of time in therapeutic range at 3 months. However, the combined PG cohort was superior to the parallel controls (percentage of out-of-range international normalized ratios 31% versus 42% at 1 month; 30% versus 42% at 3 months; percentage of time in therapeutic range 69% versus 58%, 71% versus 59%, respectively, all P <0.001). Differences persisted after adjustment for age, sex, and clinical indication. There were fewer percentage international normalized ratios ≥4 and ≤1.5 and serious adverse events at 3 months (4.5% versus 9.4% of patients, P <0.001) with PG guidance. Conclusions—: These findings suggest that PG dosing should be considered for broader clinical application, a proposal that is being tested further in 3 major randomized trials. The simpler 1-step PG algorithm provided equivalent results and may be preferable for clinical application. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00927862.

Objective: To examine the epidemiology of pediatric patient visits to emergency departments (ED). Methods: We conducted a cross-sectional study of pediatric ED visits at the participating Pediatric Emergency Care Applied Research Network (PECARN) hospitals in 2002. We provide descriptive characteristics of pediatric ED visits and a comparison of the study database to the National Hospital Ambulatory Medical Care Survey (NHAMCS). Bivariate analyses were calculated to assess characteristics associated with hospital admission, death in the ED, and length of ED visit. We also performed multivariate regression to model the likelihood of admission to the hospital. Results: Mean patient age was 6.2 years; 53.5% were boys; 47.5% black; and 43.2% had Medicaid insurance. The most common ED diagnoses were fever, upper respiratory infection, asthma, otitis media, and viral syndromes. The inpatient admission rate was 11.6%. The most common diagnoses requiring hospitalization were asthma, dehydration, fever, bronchiolitis, and pneumonia. In multivariate analysis, patients who were black or Hispanic, had Medicaid insurance or were uninsured, or were older than 1 year were less likely to be hospitalized. Demographics of the PECARN population were similar to NHAMCS, with notable exceptions of a larger proportion of black patients and of admitted patients from the PECARN EDs. Conclusion: We describe previously unavailable epidemiological information about childhood illnesses and injuries that can inform development of future studies on the effectiveness, outcomes, and quality of emergency medical services for children. Most pediatric ED patients in our study sought care for infectious causes or asthma and were discharged from the ED. Hospital admission rate differed according to age, payer type, race/ethnicity, and diagnosis.

High-density lipoprotein (HDL) is highly heterogeneous and the link of its subclasses to prognosis remains controversial. We aimed to rigorously examine the associations of HDL subclasses with prognosis in secondary prevention. We collaboratively analysed data from two, complementary prospective cohorts: the TRIUMPH study of 2465 acute myocardial infarction patients, and the IHCS study of 2414 patients who underwent coronary angiography. All patients had baseline HDL subclassification by vertical-spin density gradient ultracentrifugation. Given non-linearity, we stratified by tertiles of HDL-C and its two major subclasses (HDL₂-C, HDL₃-C), then compared multivariable-adjusted hazard ratios for mortality and mortality/myocardial infarction. Patients were middle-aged to elderly (TRIUMPH: 58.2 ± 12.2 years; IHCS: 62.6 ± 12.6 years), and the majority were men (TRIUMPH: 68.0%; IHCS: 65.5%). IHCS had lower mean HDL-C levels (34.6 ± 10.1 mg/dL) compared with TRIUMPH (40 ± 10.6 mg/dL). HDL₃-C accounted for >3/4 of HDL-C (mean HDL₃-C/HDL-C 0.78 ± 0.05 in both cohorts). During 2 years of follow-up in TRIUMPH, 226 (9.2%) deaths occurred, while death/myocardial infarction occurred in 401 (16.6%) IHCS patients over 5 years. No independent associations with outcomes were observed for HDL-C or HDL₂-C. In contrast, the lowest tertile of HDL₃-C was independently associated with >50% higher risk in each cohort (TRIUMPH: with middle tertile as reference, fully adjusted HR for mortality of HDL₃-C, 1.57; 95% CI, 1.13–2.18; IHCS: fully adjusted HR for mortality/myocardial infarction, 1.55; 95% CI, 1.20–2.00). In secondary prevention, increased risk for long-term hard clinical events is associated with low HDL₃-C, but not HDL₂-C or HDL-C, highlighting the potential value of subclassifying HDL-C.