Oseltamivir Use and Risk of Serious Neuropsychiatric Adverse Events in Children

奥司他韦的使用和儿童严重神经精神不良事件的风险

基本信息

批准号：
10576415
负责人：
James W Antoon
金额：
$ 18.53万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-01 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10576415
关键词：
ABCB1 gene Active Learning Address Adverse drug event Adverse effects Adverse event Algorithms Anti-Arrhythmia Agents Antibiotics Antiviral Agents Award Biological Blood Brain Caregivers Case Series Child Childhood Chronic Clinical Investigator Clinical Pharmacology Collaborations Communicable Diseases Consensus Coupled Data Databases Diffusion Disease Drug Interactions Drug Modulation Drug usage Ensure Evaluation Event Exposure to Family Feeling suicidal Glucocorticoids Goals High Prevalence Hospitalization Hospitals Incidence Infection Infectious Disease Epidemiology Influenza Kidney Diseases Knowledge Laboratories Leadership Life Literature Medicaid Medical Mental disorders Mentors Methodology Methods Morbidity - disease rate N-Methylaspartate Neurologic Observational Study Oseltamivir Outcome Outpatients Patients Pediatric Hospitals Pediatrics Pharmaceutical Preparations Pharmacoepidemiology Pharmacology Pharmacy facility Population Population Study Proton Pump Inhibitors Provider Psychoses Recommendation Recording of previous events Reporting Research Research Design Research Infrastructure Research Training Retrospective Studies Retrospective cohort study Risk Safety Schizophrenia Seizures Signal Transduction Suicide Surveys Symptoms System Tennessee Testing Training United States Food and Drug Administration Viral Vital Statistics Work career career development clinical care clinical practice design experience gamma-Aminobutyric Acid high risk improved influenza infection inhibitor lipophilicity medication safety mortality multidisciplinary neuropsychiatric symptom neuropsychiatry population based programs psychiatric comorbidity randomized trial secondary analysis shared decision making skills socioeconomic disadvantage

项目摘要

PROJECT SUMMARY/ABSTRACT Oseltamivir (Tamiflu) is the only Food and Drug Administration (FDA) approved influenza medication for children < 12 years. Yet, oseltamivir is under prescribed, including in children at high risk for influenza complications. One key barrier is parental and provider concern about the safety of oseltamivir. Potential adverse drug events related to oseltamivir, especially neuropsychiatric adverse effects (NPAEs), are frequently reported in the medical liter- ature and in the media. Oslemativir may cause NPAEs through direct effects on NDMA/GABA signaling in the brain, which is known to cause neurospcyahitric symptoms in diseases such as schizophrenia. Oseltamivir passively diffuses into the brain and is then rapidly exported out of the brain by the P-gp transport system. There several mechanisms that might result in high concentrations in the brain, such as through alterations in this P- gp transport. However, there is no consensus on a causal relationship between oseltamivir and NPAEs. This is in part because of the background incidence of influenza associated neuropsychiatric symptoms is not known. There is a critical need to define the true risk of NPAE in children exposed to oseltamivir to best inform clinical practice and clarify the concerns of patients, their caregivers, and providers. The aims of this project are to: 1) to define the population-based incidence of influenza associated serious neuropsychiatric symptoms in children, 2) to test the hypothesis that oseltamivir is associated with serious NPAE and 3) to test the hypothesis that concurrent use of drugs modulating P-gp modifies the risk of oseltamivir associated serious NPAE. The pro- posed studies leverage data from the Tennessee Medicaid (TennCare) program comprising vital statistics, phar- macy claims data, and hospital administrative data from more than 750,000 children per year, representing 50% of Tennessee’s children. The TennCare database overrespresents vulnerable children, including those with chronic conditions and socioeconomic disadvantages. The large number of children in this database, and long history of successful, high-impact research conducted using these data are major strengths of the current pro- posal. The results of these studies will fill an important knowledge gap regarding serious adverse drug events in children and will inform treatment for influenza. The candidate’s career goal is to emerge as an independent clinical investigator with expertise in pharmacoepidemiology and drug safety. To accomplish this goal, in addition to completion of the proposed scientific aims, the candidate will augment his prior research training with ad- vanced coursework in pharmacoepidemiology methods, training in leadership and mentoring, and practical ex- periences with the FDA and Children's Hospital Association focused on observational studies to improve pedi- atric drug safety. Throughout this award, the candidate will work closely with a multidisciplinary team of mentors and advisors-including experts in pediatrics, pharmacoepidemiology, clinical pharmacology, infectious disease and epidemiology to carry out his stated career objectives and specific aims.

项目摘要/摘要 Oseltamivir（tamiflu）是唯一获得儿童批准的影响力的食品药物管理局（FDA） <12年。然而，奥斯塔米维尔的处方不足，包括患有影响并发症的高风险的儿童。一主要障碍是父母对奥斯塔米维尔安全的关注。潜在的不良药物事件与在医学文献中经常报道oseltamivir，尤其是神经精神上的不良反应（NPAE）在媒体和媒体中。 Oslemativir可能会通过对NDMA/GABA信号的直接影响引起NPAE 大脑，已知在精神分裂症等疾病中引起神经囊肿症状。奥斯塔米维尔被动地扩散到大脑中，然后通过P-gp传输系统迅速从大脑中出口。那里几种可能导致大脑浓度高的机制，例如通过改变该p- GP运输。但是，Oseltamivir和NPAE之间的因果关系尚无共识。这是在某种程度上是由于影响型神经精神症状的背景事件的背景事件。在暴露于奥斯塔米维尔的儿童中，迫切需要定义NPAE的真正风险，以最好地告知临床实践并阐明患者，护理人员和提供者的担忧。该项目的目的是：1）为了定义与儿童的严重神经精神症状相关的基于人群的发病率， 2）检验Oseltamivir与严重NPAE相关的假设和3）检验以下假设。调节P-gp的药物的并发使用会改变奥斯塔米韦相关的严重NPAE的风险。专业人士提出的研究利用田纳西州医疗补助计划（TENNCARE）计划的数据编写了重要统计数据，梅西百货（Macy）索赔数据和每年750,000多名儿童的医院行政数据，占50％田纳西州的孩子。 Tenncare数据库过于责备的儿童，包括慢性病和社会经济障碍。该数据库中的大量儿童和长期使用这些数据进行的成功，高影响研究的历史是当前攻击的主要优势波斯。这些研究的结果将填补有关严重不良药物事件的重要知识差距儿童，并将告知影响力的治疗。候选人的职业目标是成为独立的临床研究者具有药物ePidemiology and Drug Safety的专业知识。为了实现这一目标，此外为了完成拟议的科学目的，候选人将在AD- 药物ePidemiology方法，领导力和心理培训以及实践的培训方面的课程工作与FDA和儿童医院协会的期间着重于观察性研究，以改善脚步阿特里克药物安全。通过该奖项，候选人将与多学科的导师团队紧密合作以及顾问 - 包括儿科，药物电子学，临床药理学，传染病的专家和流行病学，以实现他既定的职业目标和具体目标。