Genetic parameters for repeatedly recorded enteric methane concentrations of dairy cows.

Animal breeding techniques offer potential to reduce enteric emissions of ruminants to lower the environmental impact of dairy farming. The aim of this study was to estimate the heritability and repeatability of methane (CH4) concentrations, using the largest data set from long-term repeatedly recorded CH4 on cows to date, and to evaluate (1) the accuracy of breeding values for different CH4 traits, including using visits or weekly means, and (2) recording strategies (with varying numbers of records and recorded daughters per sire). The data comprised of long-term recording of CH4 and carbon dioxide (CO2), from 1,746 Holstein Friesian cows, on 14 commercial dairy farms throughout the Netherlands. Emissions were recorded in 10- to 35-s intervals, between 64 and 436 d, depending on farms. From each robot visit, CH4 and CO2 concentrations were summarized into various traits, averaged per visit and per week: mean, median, mean log, and mean CH4/CO2 ratio. Genetic parameters were estimated with animal repeatability models, using a restricted maximum likelihood procedure, and a relationship matrix based on genotypes and pedigree. The heritability was equal for mean and median CH4 per visit (0.13) but lower for logCH4 and CH4/CO2 (0.07 and 0.01, respectively). Phenotypic and genetic correlations were high (≥0.78) between the CH4 traits, apart from the genetic correlations with the CH4/CO2 trait, which were negative. To achieve a minimum reliability of 50% for the estimated breeding value of a bull, 25 records on mean CH4, measured on 10 different daughters, were sufficient. Although the heritability and repeatability were higher for weekly (0.32 and 0.68, respectively) than for visit mean CH4 (0.13 and 0.30, respectively), the reliabilities of estimated breeding values from visit or weekly means were equal; thus, we found no advantage in averaging records to weekly means for genetic evaluations.

Fenofibrate and warfarin interaction.

A 79-year-old man with atrial fibrillation and coronary heart disease who was taking warfarin (Coumadin) was converted to fenofibrate from gemfibrozil therapy for persistently elevated triglyceride levels. The patient took fenofibrate for 1 month and subsequently experienced rectal bleeding that required a visit to the emergency room. Before starting fenofibrate therapy, his coagulation values were within therapeutic range, but when measured in the emergency room the international normalized ratio (INR) was grossly elevated. The patient denied any changes in diet, alcohol ingestion, compliance with therapy, or use of other new drugs except for fenofibrate. His drug therapy profile consisted of digoxin, fosinopril, and furosemide for chronic heart failure, allopurinol for gout, and potassium supplementation. To minimize the risk of supratherapeutic INR values and/or hemorrhagic events, clinicians should perform serial monitoring of INR when initiating fenofibrate therapy in a patient previously stabilized on a coumarin anticoagulant.

The relationship between low-density lipoprotein cholesterol goal attainment and prevention of coronary heart disease--related events.

BACKGROUND: According to the National Cholesterol Education Program (NCEP) treatment guidelines, patients with preexisting coronary heart disease (CHD) or other atherosclerotic vascular disease should lower low-density lipoprotein (LDL) cholesterol to < or = 100 mg/dL. Recent statin trials document the benefit of cholesterol lowering on CHD events but do not address the optimal goal of LDL cholesterol. METHODS: The pravastatin to simvastatin conversion-lipid optimization program (PSCOP) at the VA San Diego Healthcare System (VASDHS) was a formulary-conversion program designed to increase the percentage of patients who meet their recommended NCEP LDL cholesterol goal. We compared the incidence of clinical outcome and mortality between CHD patients from the original PSCOP cohort with postconversion LDL cholesterol greater than and < or = 100 mg/dL. A total of 524 patients were stratified by postconversion LDL cholesterol levels (greater than [N=183]) or < or = 100 mg/dL [N=341]) and observed for a mean duration of 27.7 months. Patients' VASDHS records were reviewed for postconversion mortality from any cause and CHD-related events. Patients were mailed a questionnaire to capture similar events that may have occurred outside of VASDHS, which might not be present in the patient's VASDHS record. RESULTS: Lipid-lowering therapy < or = 100 mg/dL was associated with a significantly lower percentage of total deaths and CHD-related events (40% vs 61%, P=0.008). In patients with LDL cholesterol >100 mg/dL, the relative risk of unstable angina (relative risk, 2.2; 95% confidence interval, 1.3 to 3.8; P=0.004) and stroke (relative risk, 3.0; 95% confidence interval, 1.04 to 8.6; P=0.04) were significantly greater compared to patients meeting their LDL cholesterol goal. CONCLUSIONS: Our study results support reducing LDL cholesterol to at least 100 mg/dL in the patient with CHD.

Addressing non-adherence to antipsychotic medication: a harm-reduction approach.

This paper discusses the evidence base for interventions addressing non-adherence to prescribed antipsychotics. A case study approach is used, and the extent to which adherence improvement interventions might be used in collaboration with a specific patient is considered. The principles and application of harm-reduction philosophy in mental health are presented in a planned non-adherence harm-reduction intervention. This intervention aims to acknowledge the patient's ability to choose and learn from experience and to reduce the potential harm of antipsychotic withdrawal. The intervention evaluation method is outlined.

Colesevelam hydrochloride: a novel bile acid-binding resin.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and adverse effects of colesevelam hydrochloride, a bile acid-binding resin. METHODS: MEDLINE searches (1966-June 2000) and manufacturer prescribing literature were employed to find articles on colesevelam. Additional studies and abstracts were identified from the bibliographies of reviewed literature. STUDY SELECTION AND DATA EXTRACTION: All articles identified from data sources were evaluated, and all information deemed relevant was included in this review. Priority was given to randomized, double-blind, placebo-controlled studies. FINDINGS: Colesevelam HCl is a nonabsorbed hydrogel with bile acid sequestrant properties. Monotherapy using colesevelam in once-daily or two divided daily doses of 1.5-4.5 g has produced significant reductions in total cholesterol and low-density lipoprotein (LDL) cholesterol. Mean LDL cholesterol decreases to 20% have been noted when the patient is on 3.75-4.5 g/d. Increases in high-density lipoprotein (HDL) cholesterol have been observed (up to 9%), whereas triglycerides (TG) have increased significantly to 25% in some studies. In unpublished studies, combined use of colesevelam plus hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor have produced greater reductions in LDL cholesterol than either the statin or colesevelam administered alone. The efficacy of colesevelam monotherapy is slightly less than or similar to cholestyramine or colestipol in decreasing LDL cholesterol, although colesevelam is more potent on a gram-to-gram basis. Adverse effects have been minimal with colesevelam in published studies; this suggests an advantage over cholestyramine or colestipol therapy. Colesevelam appears to be more cost-effective than the packet dosage form of the brand formulation of the older bile acid resins. Care in selection of an appropriate agent should be exercised when considering the issues of adverse effects and palatability. CONCLUSIONS: Colesevelam alone or combined with an HMG-CoA reductase inhibitor is effective in the reduction of total and LDL cholesterol. Since colesevelam is formulated as a tablet, problems with palatability such as with the powder formulation of the bile acid-binding resins are likely to be eliminated.