Suchergebnisse

<i>Objective:</i> The purpose of our study was to evaluate the evidence on the prevalence of cytochrome P450 enzyme polymorphisms as potential genetic factors influencing drug efficacy and safety in the indigenous populations of the American hemispheres. <i>Methods:</i> We conducted a systematic review of studies published between 1985 and 2006 using the Pubmed database. <i>Results:</i> We identified only 10 original research studies on <i>CYP2A6, CYP2D6, CYP2C9, CYP2C19 </i>and <i>CYP2E1</i> in 13 indigenous American populations. Interethnic differences in the frequency of <i>CYP450</i> genetic variants existed both among the examined indigenous populations and in comparison with African, Asian and European populations. <i>Conclusions:</i> There are surprisingly few data on <i>CYP450 </i>enzyme polymorphisms in indigenous American populations, and it is difficult to draw any clear inferences about how these populations might be expected to respond to drugs in relation to other racial or ethnic groups. This lack of information could create a barrier to the use of pharmacogenetic testing in these populations. Collaborative partnerships between indigenous communities and researchers are needed to avail the clinical benefits of <i>CYP450</i> enzyme polymorphism testing to indigenous populations.

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.

Abstract Background The demand for induced abortions in Uganda is high despite legal and moral proscriptions. Abortion seekers usually go to illegal, hidden clinics where procedures are performed in unhygienic environments by under-trained practitioners. These abortions, which are usually unsafe, lead to a high rate of severe complications and use of substantial, scarce healthcare resources. This study was performed to estimate the costs associated with induced abortions in Uganda. Methods A decision tree was developed to represent the consequences of induced abortion and estimate the costs of an average case. Data were obtained from a primary chart abstraction study, an on-going prospective study, and the published literature. Societal costs, direct medical costs, direct non-medical costs, indirect (productivity) costs, costs to patients, and costs to the government were estimated. Monte Carlo simulation was used to account for uncertainty. Results The average societal cost per induced abortion (95% credibility range) was $177 ($140-$223). This is equivalent to $64 million in annual national costs. Of this, the average direct medical cost was $65 ($49-86) and the average direct non-medical cost was $19 ($16-$23). The average indirect cost was $92 ($57-$139). Patients incurred $62 ($46-$83) on average while government incurred $14 ($10-$20) on average. Conclusion Induced abortions are associated with substantial costs in Uganda and patients incur the bulk of the healthcare costs. This reinforces the case made by other researchers--that efforts by the government to reduce unsafe abortions by increasing contraceptive coverage or providing safe, legal abortions are critical.