A Novel, Single Algorithm Approach to Predict Acenocoumarol Dose Based on CYP2C9 and VKORC1 Allele Variants

The identification of CYP2C9 and VKORC1 genes has strongly stimulated the research on pharmacogenetics of coumarins in the last decade. We assessed the combined influence of CYP2C9 *2 and *3, and VKORC1 c.-1639G>A, 497C>G, and 1173C>T variants, on acenocoumarol dosage using a novel algorithm approach, in 193 outpatients who had achieved stable anticoagulation. We constructed an “acenocoumarol-dose genotype score” (AGS, maximum score = 100) based on the number of alleles associated with higher acenocoumarol dosage carried by each subject for each polymorphism. The mean AGS was higher in the high-dose (>28mg/week) compared with the low-dose (<7mg/week) group (mean(SEM) of 84.1±3.4 vs. 62.2±4.8, P = 0.008). An AGS>70 was associated with an increased odds ratio (OR) of requiring high acenocoumarol dosage (OR: 3.347; 95%CI: 1.112–10.075; P = 0.032). In summary, although more research is necessary in other patient cohorts, and this algorithm should be replicated in an independent sample, our data suggest that the AGS algorithm could be used to help discriminating patients requiring high acenocoumarol doses to achieve stable anti-coagulation

Population ecology of the sea lamprey (Petromyzon marinus) as an invasive species in the Laurentian Great Lakes and an imperiled species in Europe

The sea lamprey Petromyzon marinus (Linnaeus) is both an invasive non-native species in the Laurentian Great Lakes of North America and an imperiled species in much of its native range in North America and Europe. To compare and contrast how understanding of population ecology is useful for control programs in the Great Lakes and restoration programs in Europe, we review current understanding of the population ecology of the sea lamprey in its native and introduced range. Some attributes of sea lamprey population ecology are particularly useful for both control programs in the Great Lakes and restoration programs in the native range. First, traps within fish ladders are beneficial for removing sea lampreys in Great Lakes streams and passing sea lampreys in the native range. Second, attractants and repellants are suitable for luring sea lampreys into traps for control in the Great Lakes and guiding sea lamprey passage for conservation in the native range. Third, assessment methods used for targeting sea lamprey control in the Great Lakes are useful for targeting habitat protection in the native range. Last, assessment methods used to quantify numbers of all life stages of sea lampreys would be appropriate for measuring success of control in the Great Lakes and success of conservation in the native range

A Review of Public Policy Issues in Promoting the Development and Commercialization of Pharmacogenomic Applications: Challenges and Applications

This article reviews the regulatory, social, policy, and other issues that will shape the development of pharmacogenomics applications. We identify and analyze 19 key public policy issues, ranging from the economic incentives for linked diagnostic-drug development, to the regulation of tests and drugs, and to privacy and informed consent. Challenging technical, business, and policy-related issues might either hinder progress in the field of pharmacogenomics or potentially accelerate it, depending on how they are addressed and resolved. How well the numerous important stakeholders - both private and public - address these issues will be critical for pharmacogenomics to deliver on its promise

Stakeholder Perspectives on a Risk-Benefit Framework for Genetic Testing

A key to accelerating the appropriate integration of genomic applications into healthcare in the coming decades will be the ability to assess the tradeoffs between clinical benefits and clinical risks of genetic tests in a timely manner. Several factors limit the ability of stakeholders to achieve this objective, including the lack of direct evidence, the lack of a framework to quantitatively assess risk and benefit, and the lack of a formal analytic approach to assess uncertainty. We propose that a formal, quantitative risk-benefit framework may be particularly useful for assessing genetic tests intended to influence health outcomes, and communicating the potential clinical benefits, harms, and uncertainty to stakeholders. As part of the development process for such a framework, a stakeholder meeting was held in Seattle (Wash., USA) in December of 2008, with the objective of discussing a risk-benefit framework, using warfarin pharmacogenomics as a case study. Participants engaged in focused discussion to elucidate the potential role of genetic test risk-benefit analysis in informing decision-making, categorizing genetic tests and directing research prioritization. This research investigation focuses on qualitative analysis of responses elicited from workshop participants during the proceedings of the workshop session. The major findings of the workshop were: (1) stakeholder support for risk-benefit modeling as a tool to structure discussion of the clinical utility of genetic tests; (2) desire for the modeling process to be iterative, transparent, and parsimonious in its presentation to stakeholders, and (3) some concern with the use of quality-adjusted life-years in the evaluation process. The meeting's findings emphasize the potential utility of risk-benefit analysis in genetic test evaluation, and highlight key areas for future research and stakeholder consensus-building