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 对接受手术和儿童麻醉后神经毒性的担忧几乎持续 二十年，部分原因是没有结论性证据证明它存在，也没有足够的证据 证明事实并非如此。评估神经行为结局的大规模观察性研究 在暴露于麻醉和手术后产生了可变结果，但没有证明 可行的，无关的证据表明风险增加。该建议旨在更好地定义 暴露于麻醉和手术以及随后的神经行为疾病之间的关联（定义 作为行为破坏性疾病，情绪障碍和焦虑症），通过对现有的新分析 有可能克服先前研究局限性的医疗补助数据。这项研究使用了新的 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 手术（控制年龄，性别和种族后，近来随机的阑尾切除术）与无关 与生活方式或疾病相关的治疗，可能与长期神经行为有关 结果，（2）通过使用多元匹配技术来解释潜在的可观察 我们的队列基线差异，我们有能力比较大约68,000的裸露队列 340,000例匹配对照的儿科阑尾切除术患者，两者都可以观察到紧密平衡 并可能无法观察到的风险因素。如果存在长期关联，这使我们能够更好地学习 在全身麻醉的手术暴露与随后的不良神经行为结局之间 孩子们。最后，（3）我们还将检查一个具有急性医疗状况的68​​,000名患者的医疗对照组 例如胃肠炎，纤维炎和社区获得性肺炎，以检查神经行为疾病是否存在 在这组中不接受手术或麻醉的升高。该研究将检查多动症的结果 进行疾病，焦虑，抑郁和躁郁症，以进行多元匹配的队列研究 比较医疗补助中暴露的儿童与未暴露儿童之间的研究结果危害。我们 假设阑尾切除术患者将对这些研究结果的危害升高，因为 与对照组相比。我们将确定所有接受阑尾切除术的患者3至15岁，并且 将每个患者与5个患者相同的对照组匹配，省略任何暴露或控制患者 主要分析中神经行为疾病的基线历史或具有复杂慢性的证据 疾病，并在阑尾切除术治疗组与儿童之间进行第二个1：1的匹配 接受急性医疗状况。这项研究的结果将在阑尾切除术之外推广 正是因为阑尾炎随机发生（与年龄，性别和种族匹配之后），并且应该有助于 告知护理人员与全身麻醉和手术有关的潜在神经行为风险。