HEAL Initiative: Integrative Management of chronic Pain and OUD for Whole Recovery (IMPOWR): Research Centers

HEAL 计划：慢性疼痛和 OUD 整体康复综合管理 (IMPOWR)：研究中心

• 批准号: 10652027
• 负责人: WILLIAM C BECKER
• 金额: $ 16.36万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10652027
• 关键词: Aging; Agonist; Buprenorphine; Case Series; Case Study; Characteristics; Clinical; Cohort Studies; Collaborations; Cox Proportional Hazards Models; Data; Decision Making; Dental; Dental caries; Dose; Helping to End Addiction Long-term; High Prevalence; Hypogonadism; Impairment; Individual; Medicine; Methodology; Methods; Moods; Opioid; Opioid agonist; Oral cavity; Osteoporosis; Outcome; Patients; Pattern; Pharmaceutical Preparations; Pharmacoepidemiology; Policies; Positioning Attribute; Property; Provider; Recording of previous events; Recovery; Relative Risks; Reporting; Research; Retrospective cohort; Risk; Sampling; Societies; Time; Tooth Loss; United States Dept. of Health and Human Services; United States Food and Drug Administration; Ventilatory Depression; Veterans; Work; Xerostomia; antagonist; base; chronic pain; chronic pain management; clinical care; cohort; comparison group; data warehouse; design; experience; high risk; immune function; innovation; kappa receptors; opioid agonist therapy; opioid exposure; opioid therapy; oral infection; patient subsets; primary outcome; receptor; response; sociodemographics

Background & Significance: Chronic pain is a high prevalence problem for which full agonist opioids are commonly prescribed. Harm of full agonist opioids may outweigh benefit in which case switch to buprenorphine is often recommended. To make decisions about switching from full agonists to buprenorphine, patients and providers need valid information about benefits and harms. The FDA recently issued a warning about the use of transmucosal buprenorphine and dental problems based on an accumulated case series of approximately 315 cases without control patients. Therefore, there is a significant gap in understanding of the relative risk of dental problems between full agonist opioids and buprenorphine Innovation & Impact: Our study will harness the “Full VA” sample of the Veterans Aging Cohort Study (VACS) containing ~8 million individuals to assess the relative risk of transmucosal buprenorphine vs. full opioid agonists vs. no opioid therapy for dental problems using a rigorous cohort design, adjusting for hypothesized confounders. This innovative work will examine various patterns of opioid exposure (full agonist vs. switch to partial agonist) that reflect real-world clinical comparisons to inform risk discussions with patients. Specific Aims: 1. To determine the association between incident long-term opioid agonist (full and partial) receipt and tooth decay, cavities, oral infections, and loss of teeth (here forward referred to as composite adverse dental outcome: CADO) compared to no long-term opioid agonist receipt, adjusting for relevant sociodemographic and clinical factors. 2. Among individuals with incident long-term full agonist opioid receipt, to examine the association between patterns (stay on full opioid agonists vs. switch to buprenorphine vs. stop) of opioid receipt and CADO. 3. Among individuals with incident long term opioid receipt who do not switch, to examine the association between greater opioid exposure (mg MEDD x time = total mg MEDD) and CADO, stratified by immunosuppressive properties of individual opioids. Methodology: Based on our previous methods using VA's Corporate Data Warehouse (CDW), we will identify a large retrospective cohort of all Veterans with incident long-term opioid therapy (LTOT) over the period of 2010-2019, matched 1:2 with Veterans who lack LTOT receipt and observe the cohort over time for patterns of opioid receipt—both full and partial agonist--and adverse dental outcomes. For the primary outcome (CADO), a Cox proportional hazards model will be our primary approach to assessing pattern of opioid receipt, demographic and treatment characteristics in relation to time to outcome. In the subset of patients who receive full agonist opioids exclusively (i.e. lack partial agonist receipt), we will examine the association between total quantity of opioid exposure, immunosuppressive properties of the opioids and adverse dental outcomes. Next Steps/Implementation: Results of this study will help inform risk discussions with patients considering a switch to buprenorphine from full opioid agonists.

背景和意义：慢性疼痛是一个高患病率的问题，完全激动剂阿片类药物是 一般规定的。完全激动剂阿片类药物的危害可能超过获益，在这种情况下，改用丁丙诺啡 经常被推荐。为了决定从完全激动剂转换为丁丙诺啡，患者和 提供者需要关于益处和危害的有效信息。FDA最近发布了一项警告， 基于累积的病例系列， 315例无对照组。因此，在理解相对风险方面存在重大差距， 完全激动剂阿片类药物和丁丙诺啡之间的牙科问题 创新与影响：我们的研究将利用退伍军人老龄化队列研究（VACS）的“全VA”样本 包含约800万人，以评估经粘膜丁丙诺啡与全阿片类药物的相对风险 使用严格的队列设计，调整假设的 混杂因素。这项创新性的工作将研究阿片类药物暴露的各种模式（完全激动剂vs. 部分激动剂），反映真实世界的临床比较，为与患者的风险讨论提供信息。 具体目标：1。确定事件长期阿片类激动剂（完全和部分）之间的相关性 收据和蛀牙、蛀牙、口腔感染和牙齿脱落（此处称为复合 不良牙科结局：CADO）与未长期接受阿片类激动剂相比，调整相关 社会人口学和临床因素。2.在发生长期完全接受激动剂阿片类药物的个体中， 检查模式之间的关联（继续使用全阿片类激动剂vs.改用丁丙诺啡vs.停止） 阿片类药物和CADO 3.在长期接受阿片类药物但未转换的个体中， 检查更大的阿片类药物暴露（mg MEDD x时间=总mg MEDD）与CADO之间的关联， 根据单个阿片类药物的免疫抑制特性分层。 方法：基于我们以前使用VA公司数据仓库（CDW）的方法，我们将确定 一项大型回顾性队列研究，研究对象为在2009年至2010年期间接受过长期阿片类药物治疗（LTOT）的所有退伍军人。 2010-2019年，与缺乏LTOT接收的退伍军人1：2匹配，并随时间推移观察队列的 接受阿片类药物--包括完全和部分激动剂--和不良的牙科结果。对于主要结局（CADO），a 考克斯比例风险模型将是我们评估阿片类药物接受模式的主要方法， 与至结局时间相关的人口统计学和治疗特征。在接受了 完全激动剂阿片类药物（即缺乏部分激动剂治疗），我们将检查总阿片类药物 阿片类药物暴露量，阿片类药物的免疫抑制特性和不良牙科结果。 后续步骤/实施：本研究的结果将有助于与考虑 从完全阿片类激动剂改为丁丙诺啡。