Neurobehavioral Disorders after Appendectomy in Childhood

儿童期阑尾切除术后的神经行为障碍

• 批准号: 10159944
• 负责人: JEFFREY H SILBER
• 金额: $ 71.12万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-06 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10159944
• 关键词: 3 year old; Accounting; Acute; Address; Admission activity; Age; Anesthesia procedures; Anesthetics; Animals; Anxiety; Anxiety Disorders; Appendectomy; Appendicitis; Attention; Attention deficit hyperactivity disorder; Benefits and Risks; Bipolar Disorder; Caregivers; Cellulitis; Child; Childhood; Chronic Disease; Clinical Research; Code; Cohort Studies; Communities; Complex; Control Groups; Counseling; Data; Data Set; Diagnosis; Diagnostic; Disease; Disruptive Behavior Disorder; Drug Prescriptions; Event; Executive Dysfunction; Exposure to; Future; Gastroenteritis; General Anesthesia; General Population; Health; Heterogeneity; Hospitalization; Human; Incidence; Inflammation; Knowledge; Lead; Life Style; Mechanical ventilation; Medicaid; Medical; Mental Depression; Mood Disorders; Natural experiment; Nature; Neurocognitive; Neurodevelopmental Deficit; Neurotoxins; Observational Study; Operative Surgical Procedures; Outcome; Outcome Measure; Outcome Study; Parents; Patients; Pediatrics; Pneumonia; Population; Race; Recording of previous events; Research; Retrospective Studies; Risk; Risk Factors; Same-sex; Sample Size; Selection Bias; Stress; Techniques; Time; Work; adverse outcome; cohort; community acquired pneumonia; complex chronic conditions; hazard; lifestyle factors; neurobehavioral; neurobehavioral disorder; neurotoxic; neurotoxicity; novel strategies; primary outcome; psychological trauma; residence; sex; surgical risk

ABSTRACT Concern about neurotoxicity following exposure to surgery and anesthesia in childhood has persisted for nearly two decades, in part because there is no conclusive evidence to prove that it exists, nor is there adequate evidence to prove that it does not. Large-scale observational studies evaluating neurobehavioral outcomes after exposures to anesthesia and surgery have generated variable results, but none have demonstrated actionable, un-confounded evidence suggesting increased risk. This proposal seeks to better define the association between exposure to anesthesia and surgery and subsequent neurobehavioral disorders (defined as behavioral disruptive disorders, mood disorders, and anxiety disorders) through a new analysis of existing Medicaid data that has the potential to overcome limitations of previous studies. This study uses a new approach for examining the question by: (1) using a natural experiment that reflects a stochastic exposure to surgery (the near random event of appendectomy after controlling for age, sex and race) that is not associated with lifestyle or disease-related treatments that may themselves be associated with long-term neurobehavioral outcomes, and (2) through the use of multivariate matching techniques to account for potential observable baseline differences in cohorts, we have the ability to compare an exposed cohort of approximately 68,000 pediatric appendectomy patients with 340,000 matched controls that are closely balanced for both observable and potentially unobservable risk factors. This enables us to better study if there is a long-term association between operative exposure with general anesthesia and subsequent adverse neurobehavioral outcomes in children. Finally, (3) we will also examine a 68,000-patient medical control group with acute medical conditions such as gastroenteritis, cellulitis and, community-acquired pneumonia to examine if neurobehavioral disorders are elevated in this group not exposed to surgery or anesthesia. The study will examine outcomes of ADHD, conduct disorders, anxiety, depression and bipolar disorder, to conduct a multivariate matched cohort study to compare the hazard of study outcomes between exposed and unexposed children in Medicaid. We hypothesize that patients with appendectomy will have an elevated hazard of these study outcomes as compared to controls. We will identify all patients who underwent appendectomy from ages 3 to 15 years, and match each patient to 5 controls who were the same age, omitting any exposed or control patient with a baseline history of neurobehavioral disorders in the primary analysis or with evidence of complex chronic disease, and perform a second 1:1 match between the appendectomy treated group and children who were admitted for acute medical conditions. The results of this study will be generalizable beyond appendectomy precisely because appendicitis occurs randomly (after matching on age, sex, and race) and should aid in informing caregivers about potential neurobehavioral risks associated with general anesthesia and surgery.

抽象的 对儿童时期接受手术和麻醉后神经毒性的担忧一直持续了近 二十年，部分原因是没有确凿的证据证明它存在，也没有足够的证据 有证据证明事实并非如此。评估神经行为结果的大规模观察性研究 在接受麻醉和手术后，产生了不同的结果，但没有一个证明 可操作的、无混淆的证据表明风险增加。该提案旨在更好地定义 麻醉和手术暴露与随后的神经行为障碍（定义 （如行为破坏性障碍、情绪障碍和焦虑障碍）通过对现有的新分析 医疗补助数据有可能克服先前研究的局限性。这项研究使用了一种新的 通过以下方式检查问题的方法：（1）使用反映随机暴露的自然实验 不相关的手术（在控制年龄、性别和种族后进行阑尾切除术的近乎随机事件） 与生活方式或疾病相关的治疗，这些治疗本身可能与长期神经行为有关 结果，以及（2）通过使用多元匹配技术来解释潜在的可观察结果 队列中的基线差异，我们有能力比较大约 68,000 名暴露队列 儿科阑尾切除术患者有 340,000 名匹配的对照，这些对照在可观察到的两个方面都非常平衡 以及潜在的不可观察的风险因素。这使我们能够更好地研究是否存在长期关联 全身麻醉手术暴露与随后的不良神经行为结果之间的关系 孩子们。最后，(3) 我们还将检查 68,000 名患有急性疾病的医疗对照组 例如胃肠炎、蜂窝组织炎和社区获得性肺炎，以检查是否有神经行为障碍 在未接受手术或麻醉的这一组中，该值升高。该研究将检查多动症的结果， 进行障碍、焦虑、抑郁和双相情感障碍，进行多变量匹配队列研究 比较医疗补助中暴露和未暴露儿童之间研究结果的风险。我们 假设接受阑尾切除术的患者这些研究结果的风险会增加，因为 与对照相比。我们将识别所有 3 至 15 岁接受阑尾切除术的患者，并且 将每个患者与 5 个年龄相同的对照患者进行匹配，忽略任何具有相同年龄的暴露患者或对照患者 初步分析中神经行为障碍的基线病史或有复杂慢性病证据 并在阑尾切除治疗组和接受阑尾切除治疗的儿童之间进行第二次 1:1 匹配 因急性医疗状况入院。这项研究的结果将推广到阑尾切除术之外 正是因为阑尾炎是随机发生的（在匹配年龄、性别和种族后）并且应该有助于 告知护理人员与全身麻醉和手术相关的潜在神经行为风险。