Opiod Analgesics and the Risk of Serious Infections in Seniors

描述(申请人提供)：阿片类止痛药是美国最常见的处方药物类别之一。尽管这些药物已经用于医疗用途几十年了，但它们的安全性和有效性仍不清楚。临床试验的可用数据仅限于高度精选的患者和短期疗效结果。 令人高度关注的是，关于这些药物的安全性概况的信息甚至更少。几条体内实验证据表明，阿片类止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、潜在威胁生命的感染。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，他们通常受到持续性疼痛的影响，感染的风险已经增加。鉴于对替代镇痛剂(如非甾体类抗炎药和环氧合酶-2抑制剂)安全性的担忧，以及阿片类药物日益广泛的使用，确定和量化这一潜在风险具有重大的公共卫生利益。此外，目前有一些阿片类止痛药可用，但并不是所有的都具有相同的免疫抑制特性。确定那些倾向于促进严重感染的阿片类药物对于为老年人选择止痛药至关重要。我们建议对参加田纳西州医疗补助计划(Tennessee Medicaid)的老年人进行一项回顾性研究，具体目的如下：1)测试使用阿片类止痛剂会增加严重感染风险的假设；以及2)测试个别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身对照的病例系列设计，抵消固定的测量和未测量的混杂因素的影响，从而控制相关的时变协变量；因此，可以对相对风险进行公正的估计。

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.