Inhibition of prostacyclin and thromboxane biosynthesis in healthy volunteers by single and multiple doses of acetaminophen and indomethacin.

This double-blind, randomized crossover study assessed the effect of acetaminophen (1000 mg every 8 hours) versus indomethacin (50 mg every 8 hours) versus placebo on cyclooxygenase enzymes (COX-1 and COX-2). Urinary excretion of 2,3-dinor-6-keto-PGF1α, (prostacyclin metabolite, PGI-M; COX-2 inhibition) and 11-dehydro thromboxane B2 (thromboxane metabolite, Tx-M; COX-1 inhibition) were measured after 1 dose and 5 days of dosing. Peak inhibition of urinary metabolite excretion across 8 hours following dosing was the primary end point.

Lipid-altering efficacy of switching to ezetimibe/simvastatin 10/20 mg versus rosuvastatin 10 mg in high-risk patients with and without metabolic syndrome.

Metabolic syndrome (MetS) is a clustering of atherosclerotic coronary heart disease risk factors. This post-hoc analysis compared the effects of switching to ezetimibe/simvastatin 10/20 mg or rosuvastatin 10 mg in a cohort of 618 high-risk hypercholesterolaemic patients with (n=368) and without (n=217) MetS who had previously been on statin monotherapy. Patients were randomised 1:1 to double-blind ezetimibe/simvastatin 10/20 mg or rosuvastatin 10 mg for 6 weeks.

Influence of simvastatin, fenofibrate and/or ezetimibe on correlation of low-density lipoprotein and nonhigh-density lipoprotein cholesterol with apolipoprotein B in mixed dyslipidemic patients.

Objectives: Correlations between low-density lipoprotein cholesterol (LDL-C), or nonhigh-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (Apo B) change after statin therapy has been initiated in hypercholesterolemic patients. This post-hoc analysis studied the correlation between these parameters in patients with mixed dyslipidemia before and after receiving lipid-lowering treatment.

Results: Data from two randomized, double-blind studies of 1112 patients with mixed dyslipidemia receiving treatment (ezetimibe 10 mg, ezetimibe/simvastatin 10/20 mg, fenofibrate 160 mg, ezetimibe + fenofibrate 10/160 mg, or ezetimibe/simvastatin + fenofibrate 10/20/160 mg) were pooled.

Assessment of potential pharmacokinetic interactions of ezetimibe/simvastatin and extended-release niacin tablets in healthy subjects.

Background: Efforts to lower plasma lipid levels sometimes require multiple agents with different mechanisms of action to achieve results specified by national treatment guidelines.

Methods: This was an open-label, randomized, three-period, multiple-dose crossover study that assessed the potential for pharmacokinetic interaction between extended-release niacin and ezetimibe/simvastatin and their major metabolites. Eighteen adults received three randomized treatments: (A) extended-release (ER) niacin 1000 mg/day for 2 days, followed by 2000 mg/day for 5 days; (B) ezetimibe/simvastatin 10 mg/20 mg/day; (C) coadministration of Treatments A and B.

Effects of coadministered ezetimibe plus fenofibrate in mixed dyslipidemic patients with metabolic syndrome.

Objective: Patients with metabolic syndrome are at increased risk of atherosclerotic coronary heart disease, often have mixed dyslipidemia, and may thus require more aggressive treatment of multiple lipid parameters. The objective of this investigation was to compare the treatment response of ezetimibe co-administered with fenofibrate in mixed dyslipidemic patients with and without metabolic syndrome.

Methods: This post hoc analysis evaluated 625 patients 18-75 years of age with mixed dyslipidemia, defined as elevated low-density lipoprotein cholesterol (LDL-C) levels (130-220 mg/dL) and elevated triglycerides (TG) levels (200-500 mg/dL).

Team training in the neonatal resuscitation program for interns: teamwork and quality of resuscitations.

Objective: Poor communication and teamwork may contribute to errors during neonatal resuscitation. Our objective was to evaluate whether interns who received a 2-hour teamwork training intervention with the Neonatal Resuscitation Program (NRP) demonstrated more teamwork and higher quality resuscitations than control subjects.

Methods: Participants were noncertified 2007 and 2008 incoming interns for pediatrics, combined pediatrics and internal medicine, family medicine, emergency medicine, and obstetrics and gynecology (n = 98).

Changes in cholesterol absorption and cholesterol synthesis caused by ezetimibe and/or simvastatin in men.

This study evaluates changes in cholesterol balance in hypercholesterolemic subjects following treatment with an inhibitor of cholesterol absorption or cholesterol synthesis or coadministration of both agents. This was a randomized, double blind, placebo-controlled, four-period crossover study to evaluate the effects of coadministering 10 mg ezetimibe with 20 mg simvastatin (ezetimibe/simvastatin) on cholesterol absorption and synthesis relative to either drug alone or placebo in 41 subjects. Each treatment period lasted 7 weeks.

Pharmacokinetics of digoxin in healthy subjects receiving taranabant, a novel cannabinoid-1 receptor inverse agonist.

Introduction: Interaction studies with digoxin (Lanoxin; GlaxoSmithKline, Research Triangle Park, NC, USA), a commonly prescribed cardiac glycoside with a narrow therapeutic index and a long half-life, are typically required during the development of a new drug, particularly when it is likely that digoxin may be given to patients also treated with the new agent, taranabant--a cannabinoid-1 receptor inverse agonist--for weight loss. This study was designed to establish if this combination of therapy has the potential of a significant pharmacokinetic interaction.

Methods: This open-label, fixed-sequence, two-period study investigated whether taranabant, administered to steady state, affects the well-described single-dose pharmacokinetics of digoxin.

Respiratory syncytial virus outbreak in a long-term care facility detected using reverse transcriptase polymerase chain reaction: an argument for real-time detection methods.

Objectives: To report an outbreak of respiratory synctyial virus (RSV) in a long-term care facility (LTCF) during ongoing routine respiratory illness surveillance.

Design: Rapid antigen testing, viral culture, direct fluorescent antibody (DFA) testing, and reverse transcriptase polymerase chain reaction (RT-PCR) testing for up to 15 viruses in symptomatic residents and chart review.

Setting: A 120-bed LTCF.

Long-term (48-week) safety of ezetimibe 10 mg/day coadministered with simvastatin compared to simvastatin alone in patients with primary hypercholesterolemia.

Objective: This study evaluated the long-term safety and tolerability of ezetimibe/simvastatin coadministration therapy compared to simvastatin monotherapy in patients with primary hypercholesterolemia.

Research Design And Methods: After completing a 12-week randomized, double-blind, placebo-controlled, factorial, 10-armed study comparing ezetimibe 10 mg/simvastatin 10, 20, 40, or 80 mg; simvastatin 10, 20, 40, or 80 mg; ezetimibe 10 mg; or placebo, 768 patients entered a 48-week extension, with randomized, blinded, reassignment of the simvastatin 10 mg, ezetimibe, and placebo groups to one of the ezetimibe/simvastatin groups. Patients previously receiving ezetimibe/simvastatin combination therapy, or simvastatin 20, 40, and 80 mg monotherapy continued the same therapies in this 7-arm extension study.

VAP II analysis of lipoprotein subclasses in mixed hyperlipidemic patients on treatment with ezetimibe/simvastatin and fenofibrate.

This analysis evaluates the effects on lipoprotein subfractions and LDL particle size of ezetimibe/simvastatin with or without coadministration of fenofibrate in patients with mixed hyperlipidemia. This multicenter, double-blind, placebo-controlled, parallel-group study included 611 patients aged 18-79 years randomized in 1:3:3:3 ratios to one of four 12 week treatment groups: placebo; ezetimibe/simvastatin 10/20 mg/day; fenofibrate 160 mg/day; or ezetimibe/simvastatin 10/20 mg/day + fenofibrate 160 mg/day. At baseline and study endpoint, cholesterol associated with VLDL, intermediate density lipoprotein (IDL), LDL, and HDL subfractions was quantified using the Vertical Auto Profile II method.

Diagnosis and outcomes of enterovirus infections in young infants.

Background: Enterovirus (EV) infections commonly cause fever in infants younger than 90 days of age. The polymerase chain reaction (PCR) has improved our ability to diagnose EV infections.

Objective: To evaluate the utility of blood and cerebrospinal fluid (CSF) specimens for the diagnosis of EV infections by PCR and to describe a large cohort of EV-infected infants.

Serious bacterial infections in febrile infants 1 to 90 days old with and without viral infections.

Objective: The risk of serious bacterial infection (SBI) in febrile infants who are classified as low risk (LR) or high risk (HR) by the Rochester criteria has been established. LR infants average a 1.4% occurrence of SBI, whereas HR infants have an occurrence of 21%.

Human herpesvirus 6 infection in febrile infants ninety days of age and younger.

Background: The importance of human herpesvirus 6 (HHV-6) as a pathogen in febrile infants
Objective: To determine whether febrile infants 90 days of age and younger evaluated for sepsis have evidence of HHV-6 DNA in plasma or cerebrospinal fluid (CSF).

Methods: Febrile infants View Article and Find Full Text PDF