预测术后恶心和吐的多基因评分:回顾性衍生和验证队列研究
Nicholas J Douville1, Lisa Bastarache2, Jing He2
1Department of Anesthesiology, Michigan Medicine, Ann Arbor, Michigan; and Institute of Healthcare Policy and Innovation and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan.
Anesthesiology
|September 9, 2024
概括
遗传因素有助于术后恶心和吐 (PONV) 风险,但临床因素仍然更为重要. 多基因风险评分显示与PONV的小关联,并没有有意义地改善临床预测.
科学领域:
- 麻醉学 麻醉学
- 遗传学 是一个遗传学.
- 药物基因组学 药物基因组学
背景情况:
- 手术后恶心和吐 (PONV) 显著影响患者满意度和意外入院.
- 传统的风险因素不能完全解释PONV的变异性,这表明潜在的遗传成分.
- 这项研究调查了遗传学在PONV风险中的作用.
研究的目的:
- 为PONV.进行全基因组关联研究 (GWAS).
- 开发和验证PONV.的多基因风险评分 (PRS).
- 将遗传风险的预测值与已知的PONV临床风险因素进行比较.
主要方法:
- 来自两个大型队列 (密歇根医学和范德比尔特大学医学中心) 的GWAS数据的元分析.
- 使用衍生队列 (Vanderbilt) 的数据开发PRS.
- 在独立队列 (密歇根医学) 中验证PRS,通过c统计和净重新分类指数评估预测改进.
主要成果:
- 确定了46种与PONV相关的遗传变异 (P < 1×10-5).
- 在所有模型中,标准化的多基因分数与PONV相关,每SD增加的赔率比为1.027 (P=0.044).
- 该PRS略有改善了模型歧视 (c-统计0.616对比0.613,P=0.028) 和重新分类 (4.6%).
结论:
- 虽然多基因风险评分显示了与PONV的统计学上显著的关联,但其预测影响远远小于已知的临床风险因素.
- 对PONV风险的遗传贡献在临床上不足以显著地改善对现有临床评估的预测.
- 目前的临床风险因素仍然是预测和管理PONV的主要决定因素.
相关概念视频
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists
154
Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy. SP binds and activates...
154
Sensitivity, Specificity, and Predicted Value
220
In healthcare diagnostics, laboratory tests play a crucial role in identifying and diagnosing a wide range of medical conditions. However, interpreting test results is not always straightforward. An abnormal test result does not always confirm the presence of a disease, just as a normal result does not guarantee its absence. To assess the reliability of these diagnostic tools, healthcare practitioners rely on two key statistical indicators: sensitivity and specificity.
Sensitivity is the...
Sensitivity is the...
220
Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches
124
Biopharmaceutical studies constitute a vital field aiming to enhance drug delivery methods and refine therapeutic approaches, drawing upon diverse interdisciplinary knowledge. In research methodologies, the choice between controlled and non-controlled studies significantly influences the study's reliability and accuracy.
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast,...
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast,...
124
Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists
181
5-HT3 receptor antagonists, such as dolasetron, granisetron (Kytril), ondansetron (Zofran), and palonosetron (Axoli), are crucial in managing chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea. These drugs selectively block 5-HT3 receptors in the visceral vagal and spinal afferent nerves, chemoreceptor trigger zone, and the vomiting center. They have a rapid onset of action and can be given as a single dose before chemotherapy. Ondansetron and granisetron, in particular,...
181


