Statistical Methods of Cardiotoxicity Studies in Aids

艾滋病心脏毒性研究的统计方法

• 批准号: 7161481
• 负责人: Stuart R. Lipsitz
• 金额: $ 26.54万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7161481
• 关键词: AIDS; AIDS /HIV diagnosis; AIDS therapy; antiAIDS agent; blood pressure; cardiovascular disorder epidemiology; children; cytotoxicity; disease /disorder onset; disease /disorder proneness /risk; heart dimension /size; heart disorder; heart disorder diagnosis; heart function; human data; longitudinal human study; mathematical model; medical complication; method development; model design /development; pediatric AIDS; statistics /biometry; therapy adverse effect; vertical transmission

DESCRIPTION (provided by applicant): Data from longitudinal studies have suggested that patients infected with HIV-1 might have cardiovascular abnormalities. These abnormalities may be the result of the treatments (AZT, etc.) or the HIV-1 virus itself. In this grant, we will develop methods to analyze longitudinal and survival studies of heart function in AIDS patients. Cardiotoxicity in AIDS patients could be a leading cause of morbidity and mortality. Development of methods leading to increased understanding of the cardiotoxicity could prove invaluable in determining the appropriate time to give cardioprotective therapies. The developed methods will be applied to the Pediatric Pulmonary and Cardiac Complications (P2C2) of Vertically Transmitted HIV Infection Study, which was a large, prospective longitudinal study designed to monitor heart disease and the progression of cardiac abnormalities in children born to HIV-infected women. To truly understand the change in heart function over time, new models and methods need to be developed that take into account multiple measures of heart function (LV mass, end-diastolic dimension, end-systolic dimension, fractional shortening, etc.). The models and associated statistical methods should be such that biases do not result because of higher rates of clinic visits by sicker patients, higher chance of dropout for sicker patients, missed clinic visits due to patients' health conditions, etc. In this grant, we develop appropriate models and methods to deal with these situations. We will examine the following six Specific Aims. Regression models for Longitudinal Discrete and Continuous Outcomes; A likelihood method for Longitudinal Studies with Informative Dropout; A Protective Estimator for Mixed Discrete and Continuous Outcomes Subject to Nonignorable Non-monotone Missingness; Methods for Estimation in Longitudinal Studies with Outcome-Dependent Follow-Up; and Prediction in Multivariate Survival Models; Sensitivity Analysis for the previous six aims.

描述（由申请人提供）：来自纵向研究的数据表明，感染HIV-1的患者可能有心血管异常。这些异常可能是治疗（AZT等）或HIV-1病毒本身的结果。在这项资助中，我们将开发方法来分析艾滋病患者心功能的纵向和生存研究。艾滋病患者的心脏毒性可能是发病和死亡的主要原因。方法的发展导致对心脏毒性的了解增加，在确定给予心脏保护治疗的适当时间方面可以证明是无价的。所开发的方法将应用于儿童肺部和心脏并发症（P2C2）垂直传播艾滋病毒感染研究，这是一项大型前瞻性纵向研究，旨在监测艾滋病毒感染妇女所生儿童的心脏病和心脏异常进展。为了真正了解心功能随时间的变化，需要开发新的模型和方法，考虑多种心功能测量（左室质量、舒张末期尺寸、收缩末期尺寸、分数缩短等）。模型和相关的统计方法应该是这样的，即偏差不会因为病情较重的患者就诊率较高、病情较重的患者退学的机会较高、因患者健康状况而错过的门诊就诊等而产生。在这项资助中，我们开发了适当的模型和方法来处理这些情况。我们将研究以下六个具体目标。纵向离散和连续结果的回归模型信息性退出纵向研究的似然方法具有不可忽略非单调缺失的离散与连续混合结果的保护估计结果相关随访纵向研究的估计方法多变量生存模型的预测；前六个目标的敏感性分析。