Neurocognitive Disorder after Appendectomy in the Elderly: A Natural Experiment

摘要 手术和麻醉后长期认知障碍的担忧一直存在 在过去的二十年里，部分原因是没有确凿的证据;大规模的研究没有 明确证明麻醉暴露与手术暴露以及随后的 阿尔茨海默病和相关疾病（ADRD）的发生，也没有表现出强烈的 有证据表明风险增加。该建议旨在更好地探讨 通过对现有医疗保险数据的新分析， 克服以往研究局限性的潜力。这项研究使用了一种新的解决方案， 分析医疗保险索赔（虚拟研究数据中心（VRDC）），让研究人员，在一个经济， 通过一个安全的远程服务器，以一种完全可行的方式分析自1999年以来的所有CMS数据。（1）利用 自然实验，反映了暴露于手术（阑尾切除术的事件），但与 生活方式或疾病相关治疗本身可能与认知的长期变化有关， 和（2）通过使用多变量匹配来解释队列中潜在的可观察差异，我们 有能力将80，000例阑尾切除术病例的暴露队列与匹配的对照进行比较， 密切平衡可观察和潜在不可观察的风险因素。这使我们能够更好 进行一项大规模的研究，确定手术暴露和手术后的疼痛之间是否存在长期联系。 随后的神经认知下降率。目标1将完善基于索赔的诊断定义， 通过对收集的神经认知测试结果验证Medicare索赔数据， 对医疗保险受益人的样本，由健康和退休研究，国家健康和老龄化 趋势研究和长期护理最小数据集中的临床评估数据。目标2将使用这些 定义进行多变量匹配队列研究，以比较神经认知功能障碍的风险。 发生阑尾炎随机事件导致阑尾切除术的患者减少， 未做阑尾切除术的对照组。我们假设阑尾切除术的病例 与对照组相比，神经认知能力下降的风险升高。我们会找出所有 年龄在68至77岁之间的阑尾切除术，并将每个病例与5名年龄相同且非常 对神经认知能力下降的危险因素，如糖尿病、中风和高血压，以及 广泛的合并症列表，在同一时间点的情况下发展阑尾炎，而正是 匹配那些已经显示出神经认知异常诊断代码的患者， 在比赛前进行麻醉。将通过研究以下风险比来检查结果： 暴露于对照组将包括：神经认知能力下降的诊断，疗养院入院，神经- 在疗养院进行认知测试，使用专门指示神经认知能力下降的药物，以及死亡率。 1

ABSTRACT Concern about long-term cognitive impairment following exposure to surgery and anesthesia has persisted over the past two decades, in part because there is no conclusive evidence; large-scale studies have not definitively demonstrated a lack of association between exposures to anesthesia and surgery and subsequent occurrences of Alzheimer’s disease and related disorders (ADRD), nor have they demonstrated strong evidence suggesting there is increased risk. This proposal seeks to better explore the association between operative exposure and neurocognitive decline through a new analysis of existing Medicare data that has the potential to overcome limitations of previous studies. This study uses a new solution for accessing and analyzing Medicare claims (the Virtual Research Data Center (VRDC)), allowing researchers, in an economi- cally feasible manner, to analyze all CMS data since 1999 through a secure remote server. By (1) utilizing a natural experiment that reflects an exposure to surgery (the event of appendectomy) but is not associated with lifestyle or disease related treatments that may themselves be associated with long-term changes in cognition, and (2) through the use of multivariate matching to account for potential observable differences in cohorts, we have the ability to compare an exposed cohort of 80,000 appendectomy cases with matched controls that are closely balanced for both observable and potentially unobservable risk factors. This enables us to better conduct a large-scale study determining if there is a long-term association between operative exposure and the rate of subsequent neurocognitive decline. Aim 1 will refine claims-based definitions of diagnoses that identify neurocognitive decline through validation of Medicare claims data against neurocognitive test results collected on samples of Medicare beneficiaries by the Health and Retirement Study, the National Health and Aging Trends Study, and clinical assessment data in the Long Term Care Minimum Data Set. Aim 2 will use these definitions to conduct a multivariate matched cohort study to compare the hazard for developing neurocognitive decline in patients who experienced the random event of appendicitis leading to an appendectomy versus controls who did not undergo an appendectomy. We hypothesize that cases with appendectomy will have an elevated hazard of neurocognitive decline as compared to controls. We will identify all patients who underwent appendectomy between ages 68 to 77 and match each case to 5 controls who were the same age and very similar on risk factors for neurocognitive decline such as diabetes, stroke and hypertension, as well as an extensive list of comorbidities, at the same point in time as the case developed appendicitis, while exactly matching patients who already show diagnostic codes for neurocognitive abnormalities and also controlling for anesthesia exposure prior to the match. Outcomes that will be examined by studying the hazard ratio of exposed to control groups will include: diagnoses of neurocognitive decline, nursing home admission, neuro- cognitive testing at the nursing home, drugs that specifically indicate neurocognitive decline, and mortality. 1