Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Variations in blood transfusions among newborn intensive care units. SNAP II Study Group

OBJECTIVES: Very low birth weight (\u3c 1500 g) infants frequently require packed red blood cell transfusions, and transfusion rates vary among neonatal intensive care units (NICUs). We analyzed transfusions and compared outcomes among NICUs. STUDY DESIGN: In a 6-site prospective study, we abstracted all newborns weighing \u3c 1500 g (total = 825) born between October 1994 and September 1995. Transfusion frequency and volume and phlebotomy number were analyzed by site and adjusted for birth weight and illness severity. We compared rates of intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, growth, and length of stay between the high and low transfuser NICUs. RESULTS: Sites differed significantly in mean birth weight, illness severity, number of transfusions, pretransfusion hematocrit, blood draws, and donor number. Multivariate adjustment for these risks showed that the highest transfusing NICU transfused an additional 24 cc/kg per baby during the first 14 days and 47 cc/kg per baby after 15 days, relative to the lowest transfusing NICU. The presence of arterial catheters increased the frequency of blood transfusions. The rates of intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia were not higher in the 2 lowest transfusing NICUs, nor were there differences in 28-day weight gain or length of stay. CONCLUSIONS: Major differences in transfusion practices for very low birth weight infants exist among NICUs. Because clinical outcomes were no different in lower transfuser NICUs, it is likely that transfusion and phlebotomy guidelines could result in fewer transfusions, fewer complications, and reduced cost

Inter-NICU variation in rates and management of thrombocytopenia among very low birth-weight infants

OBJECTIVES: To investigate variation among neonatal intensive care units (NICUs) in prevalence and management of thrombocytopenia in infants and(SNAP). Platelet counts in the first 12 hours after birth and on day 3 of life were abstracted from the infants\u27 medical records. Thrombocytopenia was determined from the lowest platelet count in each of these time periods. RESULTS: There was variability in rates of thrombocytopenia among NICUs, even after controlling for risk factors (e.g., SNAP, small for gestational (SGA) age and maternal hypertension). One site had a high prevalence of thrombocytopenia, but the lowest percentage of infants with thrombocytopenia who received platelet transfusions. After controlling for SNAP, GA, SGA, Apgar score and incidence of thrombocytopenia, the odds of receiving platelets at this site, relative to the site with the highest transfusion rate, was 0.10 (95% CI 0.02 to 0.43). CONCLUSIONS: This multicenter study finds a 10-fold variation among NICU in the administration of platelets to their thrombocytopenic infants that cannot be explained by presence of thrombocytopenia or illness severity

Farmer perspectives on benefits of and barriers to extended crop rotations in Iowa, USA

Abstract The highly specialized maize (Zea mays L.) and soybean [Glycine max (L.) Merr.] production system that dominates midwestern U.S. agriculture has led to widespread on‐farm and off‐farm degradation of and damage to natural resources. The practice of extending maize–soybean rotations with small grains and forages has great potential to balance production and environmental goals, but adoption of these practices is low. Because little is known about farmers’ perspectives on extended rotations, we conducted social survey research with Iowa farmers to address this knowledge gap. Results show that farmers understand the potential benefits of extended rotations using small grains, but they perceive major barriers to use. The highest‐rated barriers were structural, such as lack of markets. Structural barriers cannot be easily addressed by individual farmers, indicating that efforts to address negative impacts of specialized commodity production through extended rotations with small grains will require transformative changes in agri‐food policies, programs, and ultimately markets