Opiod Analgesics and the Risk of Serious Infections in Seniors

描述（由申请人提供）：阿片类镇痛药是美国最常用的处方药类别之一。尽管这些药物已经用于医疗用途几十年，但其安全性和有效性仍不清楚。来自临床试验的可用数据仅限于高度选择的患者和短期疗效结局。 令人非常关切的是，关于这些药物安全性的信息甚至更少。几条体内实验证据表明，阿片类镇痛剂具有显著的免疫抑制特性，可能使阿片类药物使用者容易受到严重的、可能危及生命的感染。阿片类镇痛剂的免疫抑制作用对老年人来说可能特别麻烦，他们通常受到持续疼痛的影响，并且感染的风险已经增加。鉴于对替代镇痛药（例如NSAID和考克斯-2抑制剂）安全性的担忧，以及阿片类药物的日益广泛使用，确定和量化这种潜在风险具有重大的公共卫生意义。此外，目前有许多阿片类镇痛剂，但并非所有药物都具有相同的免疫抑制特性。确定那些具有最低倾向性的阿片类药物，以促进严重感染将是至关重要的，为老年人选择镇痛药。我们建议对参加TennCare（田纳西州医疗补助计划）的老年人进行一项回顾性研究，具体目的如下：1）检验使用阿片类镇痛药会增加严重感染风险的假设; 2）检验单个阿片类药物严重感染风险存在差异的假设。拟议的研究将使用自我对照病例系列设计，其中病例作为其自身对照，抵消固定测量和未测量混杂因素的影响，允许控制相关随时间变化的协变量;因此，允许对相对风险进行无偏估计。 公共卫生相关性：长期以来，人们一直担心阿片类药物会改变免疫系统反应并增加感染风险。这些问题与老年人特别相关，他们通常受到疼痛的影响，感染的风险增加。鉴于阿片类镇痛剂的广泛使用，确定和量化这一潜在风险具有重大的公共卫生意义。此外，确定那些阿片类药物的最低倾向，以促进感染将是至关重要的，以告知选择镇痛药的老年患者。

DESCRIPTION (provided by applicant): Opioid analgesics are one of the most commonly prescribed medication classes in the United States. Although these medications have been available for medical use for decades, their safety and effectiveness remain unclear. Available data from clinical trials are limited to highly selected patients and short term efficacy outcomes. Of great concern, information on the safety profile of these medications is even more scant. Several lines of in vivo experimental evidence indicate that opioid analgesics have significant immunosuppressive properties and could render opioid users susceptible to serious, potentially life-threatening infections. The immunosuppressive effects of opioid analgesics could be particularly troublesome for the elderly, who are commonly affected by persistent pain and are already at increased risk for infections. Given concerns about the safety of alternate analgesics (e.g. NSAIDs and COX-2 inhibitors), and the increasing widespread use of opioids, the determination and quantification of this potential risk is of great public health interest. Furthermore, there are a number of opioid analgesics currently available, but not all are expected to have the same immunosuppressive properties. Identifying those opioids with the lowest propensity to facilitate serious infections will be crucial to inform the selection of analgesics for the elderly. We propose to conduct a retrospective study of elderly persons enrolled in TennCare (Tennessee Medicaid) with the following specific aims: 1) To test the hypothesis that use of opioid analgesics increases the risk of serious infections; and, 2) To test the hypothesis that there is variation of the risk of serious infections for individual opioids. Th proposed studies will use a self-controlled case-series design, in which cases serve as their own controls, cancelling out the effects of fixed measured and unmeasured confounders, allowing control of relevant time-varying covariates; and, thus, allowing an unbiased estimation of the relative risk. PUBLIC HEALTH RELEVANCE: There is a long-standing concern that opioids can modify the immune system response and increase the risk of infections. These concerns are particularly relevant for elderly persons, who are commonly affected by pain and at increased risk for infections. Given the widespread use of opioid analgesics, the determination and quantification of this potential risk is of great public health interest. Moreover, identifying those opioids withthe lowest propensity to facilitate infections will be crucial to inform the selection of analgesics fo elderly patients.