Cardiovascular Risks of Prescription Amphetamine Use in a National Veterans Study

全国退伍军人研究中使用处方安非他明的心血管风险

• 批准号: 8242489
• 负责人: Arthur Westover
• 金额: $ 17.12万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8242489
• 关键词: 18 year old; Accounting; Acute myocardial infarction; Address; Adult; Adverse event; Affect; Age; Alcohol or Other Drugs use; Amphetamines; Area; Attention deficit hyperactivity disorder; Award; Brain hemorrhage; Cardiovascular Diseases; Cardiovascular system; Caring; Cause of Death; Cessation of life; Clinical; Cohort Studies; Complex; Data; Dementia; Diagnosis; Disease; Disease Outcome; Dissection; Dose; Drug effect disorder; Elderly; Epidemiologic Studies; Epidemiologist; Epidemiology; Ethnic Origin; Event; Exposure to; Future; Grant; Health Services; Health Services Research; Ischemic Stroke; Knowledge; Label; Link; Logistic Regressions; Major Depressive Disorder; Measures; Medical; Medical center; Medicare; Mental Depression; Mentors; Methodology; Methods; Methylphenidate; Modeling; Myocardial Infarction; Observational Study; Outcome; Patients; Pattern; Pharmaceutical Preparations; Pharmacoepidemiology; Pharmacy facility; Physicians; Physiological; Population; Provider; Public Health; Publishing; Race; Research; Research Personnel; Risk; Risk Factors; Safety; Selection Bias; Staging; Statistical Methods; Stroke; Subgroup; Substance Use Disorder; System; Techniques; Time; Training; Uncertainty; United States; United States National Institutes of Health; Veterans; Work; cardiovascular disorder risk; cardiovascular risk factor; career; cohort; comparative effectiveness; design; effectiveness research; experience; human old age (65+); improved; innovation; multidisciplinary; novel; older patient; primary outcome; skills

DESCRIPTION (provided by applicant): Currently there are tremendous gaps in our knowledge of who is being prescribed amphetamines, for what indications, and their long term cardiovascular safety. Amphetamines are the 2nd fastest growing class of drugs in the US, driven in part by increasing diagnoses of Attention Deficit Hyperactivity Disorder (ADHD)-which is estimated to affect 1 in 20 adults. Their use for non-FDA approved conditions, like depression, is also expanding. Prior studies indicate that misuse of amphetamines (i.e. abuse) greatly increases the risk of heart attack, stroke, and aortic dissection. While there are physiological reasons to suspect that medical use of prescription amphetamines may increase risk of cardiovascular disease (CVD) outcomes, published epidemiological studies have not answered this question. This national retrospective cohort study of patients treated in the Veterans Affairs (VA) medical system (n=8,000,000; from 2000 to 2008) proposes to: 1) describe the pharmacoepidemiology of prescription amphetamine use, 2) determine which patients are most at risk to progress from medical use to abuse of prescription amphetamines, 3) address the extent to which the medical use of prescription amphetamines is related to CVD outcomes, and 4) if prescription amphetamine use does increase risk of CVD outcomes, describe what subgroups of patients are most at risk. The primary CVD endpoint is a composite outcome of stroke, myocardial infarction, and CVD death. Exposure to prescription amphetamines will be determined using cumulative dose, which accounts for time, dose, and type of amphetamine. Three traditional statistical analytical approaches that seek to adjust for important measured and unmeasured factors that can cause biases in observational studies will be employed: 1) multiple regression, 2) propensity scoring, and 3) instrumental variable estimation. We will also use a novel, more computationally complex and sophisticated statistical approach, called Robust Latent Variable technique (RLV) to adjust for potential biases. RLV is an innovative methodology that has been developed with NIH support over the past ten years which has a number of advantages over propensity scoring and instrumental variable approaches. It incorporates advances for: 1) adjusting for selection bias, 2) minimizing model misspecification, 3) accounting for missing data in the presence of model misspecification, and 4) performing most probable model building to address model uncertainty. These innovative techniques have the potential to broadly impact the analysis of observational studies and advance methods for future comparative effectiveness research. This career award includes a multidisciplinary training plan for obtaining advanced skills in epidemiology, health services research, substance use disorders, and advanced statistical methods. It also includes a multidisciplinary team of mentors with extensive experience in all of these areas with access to national VA data. The results will provide guidance to patients, clinicians, and policymakers regarding the use and safety of prescription amphetamines. PUBLIC HEALTH RELEVANCE: Use of prescription amphetamines is rapidly increasing among adults in the United States. Who is being prescribed amphetamines, for what conditions, and whether they increase the risk of adverse cardiovascular events (death, stroke, and heart attack), is poorly understood. This national retrospective cohort study of prescription amphetamine use among veterans (from 2000 to 2008) will provide guidance to patients, clinicians, and policymakers regarding the use and safety of prescription amphetamines.

描述（由申请人提供）：目前，我们知道谁被开处方的苯丙胺，迹象及其长期心血管安全方面存在巨大差距。苯丙胺是美国第二快的药物类别，部分原因是增加注意力缺陷多动障碍（ADHD）的诊断，估计会影响20名成年人中的1个。它们用于非FDA批准的条件，例如抑郁症，也正在扩大。先前的研究表明，滥用苯丙胺（即滥用）大大增加了心脏病发作，中风和主动脉夹层的风险。尽管有生理原因怀疑处方苯丙胺的医疗使用可能会增加心血管疾病（CVD）结局的风险，但发表的流行病学研究尚未回答这个问题。这项国家回顾性队列研究对退伍军人事务（VA）医疗系统（n = 8,000,000;从2000年到2008年）的患者提出了：1）描述：1）描述处方药的药物epipidemiologicemiology of Perfercription Anpercipidemiology of Percription percription epipidemiology of哪些患者在哪些患者中确定哪些患者在滥用处方的范围内的医疗用途中最大程度地取得了最大的危险结果，以及4）如果处方苯丙胺的使用确实会增加CVD结局的风险，请描述哪些患者的亚组最有风险。主要CVD端点是中风，心肌梗塞和CVD死亡的综合结果。暴露于处方苯丙胺将使用累积剂量确定，该剂量解释了苯丙胺的时间，剂量和类型。将采用三种传统的统计分析方法，试图调整可能导致观察性研究中可能导致偏见的重要测量和未测量因素：1）多重回归，2）倾向评分，3）仪器变量估计。我们还将使用一种新颖，计算更复杂和复杂的统计方法，称为鲁棒潜在变量技术（RLV）来调整潜在偏见。 RLV是一种创新的方法，在过去十年中，它在NIH支持方面已经开发，其优势比倾向评分和仪器变量方法具有许多优势。它结合了以下方面的进步：1）调整选择偏差，2）最小化模型错误指定，3）在存在模型错误指定的情况下丢失数据，以及4）执行最可能的模型构建以解决模型不确定性。这些创新的技术有可能广泛影响观察研究的分析和进步方法，以实现未来的比较有效性研究。该职业奖包括一项多学科培训计划，用于获得流行病学，健康服务研究，药物使用障碍和高级统计方法的高级技能。它还包括一个多学科的导师团队，在所有这些领域都有丰富经验，可以使用国家VA数据。结果将为患者，临床医生和决策者提供有关处方苯丙胺的使用和安全性的指导。 公共卫生相关性：在美国成年人中使用处方苯丙胺的使用正在迅速增加。对谁被开处方的苯丙胺，在什么情况下以及是否增加了不良心血管事件（死亡，中风和心脏病发作）的风险。这项国家回顾性队列研究对退伍军人的处方苯丙胺使用研究（从2000年到2008年）将向患者，临床医生和决策者提供有关处方苯丙胺的使用和安全性的指导。