Adult Outcomes of Juvenile Idiopathic Arthritis

描述(由申请人提供)：拟议的职业发展奖旨在支持Aimee O.Hersh博士转变为独立的内科科学家，致力于改善青少年特发性关节炎(JIA)患者的预后。赫什医生是 犹他大学的一位儿科风湿病专家。她以前接受过卫生服务研究方面的培训，并将研究生涯的重点放在了解儿童发病的风湿病的成人后果上。这一奖项将使赫什博士能够完成对JIA自然历史的独特研究，并描述JIA基因和疾病表型之间的关系。为了实现这一目标，赫什博士的职业发展计划是获得结果研究方面的高级方法技能，并通过完成犹他大学的个性化医疗证书计划，获得关于基因对疾病和结果的贡献的培训。赫什博士的指导团队由约翰·本萨克博士和萨姆帕特·普拉哈拉德博士领导，他们是儿科风湿病专家，在青少年特发性关节炎的结局和这种疾病的遗传决定因素方面拥有专业知识。此外，她还组建了一个在人口和遗传流行病学方面具有专业知识的多学科咨询团队，包括复杂自身免疫性疾病的遗传学，以及JIA的结果，包括关节炎患者的残疾和生活质量的衡量。赫什博士的主要职业目标是确定儿童期风湿病患者长期预后的生物学/遗传学和非生物学预测因素，并改善这类患者的预后。她的短期职业目标是成为青少年特发性关节炎成人结局领域的专家，包括遗传易感性和预后之间的关系。赫什博士的长期职业目标是成为一名成功的内科科学家，他将：1.成为一名首席研究员，能够领导多学科研究团队并与其合作，开发最佳方法来衡量儿童期风湿病和其他儿科慢性病患者的成人结局。2.成为设计干预措施的国家专家和领导者，以改善儿童发病的风湿病患者的预后。3.成为不同学科的初级调查人员的导师。环境：犹他大学有几个独特的资源，Hersh博士将在她的研究提案和培训中利用这些资源，包括儿童风湿病山间各州数据库(ISDCRD)和犹他州人口数据库(UPDB)。她将通过完成个性化医疗证书课程获得基本的研究技能。犹他大学和儿科系拥有卓越的资源，致力于临床研究方面的指导和早期职业发展和培训，包括该大学的临床和翻译中心 科学，NIH资助的翻译和比较有效性研究的培训计划，以及儿科临床和翻译学者计划。赫什博士目前有75%的受保护时间，这将在整个获奖期内得到保证，以利用这些资源实现她的职业发展目标。研究：赫什博士的研究提案包含了三个相关的研究项目，重点描述了JIA的长期结果。幼年特发性关节炎(JIA)是最常见的儿科风湿病；大多数JIA儿童在成年后仍有持续性关节炎。贾樟柯与关节损伤、生长障碍、心血管疾病和死亡率等早产儿有关；然而，人们对这种慢性风湿病的长期后果知之甚少。这一提议的中心假设是存在不可修改的(例如，遗传)和可改变的(例如，治疗、行为)危险因素，如果被发现，将导致改善JIA儿童的治疗和结果的目标。在目标1中，赫什博士将把ISDCRD与UPDB联系起来，检查JIA的重要结果，包括整形外科手术、心血管事件和恶性肿瘤的发生率，以及不孕不育和早期死亡的风险。在目标2中，她将开发一个成年JIA患者的纵向队列，以描述该队列的残疾和生活质量结果，以及这些结果的预测因素。在目标3中，她将探索遗传易感基因与JIA治疗反应之间的关系。 这项研究的初步数据将被用于开发干预措施，以改善儿童期发病的风湿病患者的健康结果。这项建议旨在促进赫什博士作为一名独立调查员的职业生涯，致力于改善对患有慢性风湿病的儿科患者的护理。

DESCRIPTION (provided by applicant): The proposed career development award is designed to support the transition of Dr. Aimee O. Hersh into an independent physician-scientist dedicated to improving outcomes for patients with juvenile idiopathic arthritis (JIA). Dr. Hersh is a pediatric rheumatologist at the University of Utah. She has prior training in health services research and has focused her research career on understanding the adult outcomes of childhood-onset rheumatic disease. This award would allow Dr. Hersh to complete a unique study of the natural history of JIA, as well as to describe the relationship between JIA genotype and disease phenotype. To achieve this, Dr. Hersh's career development plan is to gain advanced methodological skills in outcomes research, and to obtain training in the genetic contribution to disease and outcomes through completion of the Certificate Program in Personalized Health Care at the University of Utah. Dr. Hersh's mentoring team is led by Drs. John Bohnsack and Sampath Prahalad, pediatric rheumatologists with expertise in the outcomes of juvenile idiopathic arthritis and the genetic determinants of this condition. Additionally, she has assembled a multidisciplinary advisory team with expertise in population and genetic epidemiology, including the genetics of complex autoimmune disease, as well as the outcomes of JIA, including the measurement of disability and quality of life for patients with arthritis. Dr. Hersh's overarching career goal is to determine the biologic/genetic and non-biologic predictors of long- terms outcomes of patients with childhood-onset rheumatic disease, and to improve outcomes for this patient population. Her short-term career goal is to become an expert in the area of adult-outcomes of juvenile idiopathic arthritis, including the relationship between genetic susceptibility and outcomes. Dr. Hersh's long-term career goal is to become a successful physician-scientist who will: 1. Be a principal investigator able to lead and collaborate with multidisciplinary teams of researchers to develop the best methodology to measure adult outcomes for patients with childhood-onset rheumatic disease and other pediatric-onset chronic illnesses. 2. Be a national expert and leader designing interventions to improve outcomes for patients with childhood-onset rheumatic disease. 3. Be a mentor for junior investigators across various disciplines. Environment: The University of Utah has several unique resources which Dr. Hersh will utilize for her research proposal and training, including the Intermountain States Database of Childhood Rheumatic Diseases (ISDCRD) and the Utah Population Database (UPDB). She will gain essential research skills through completion of the Certificate Program in Personalized Healthcare. The University of Utah and Department of Pediatrics have outstanding resources dedicated to mentorship and early career development and training in clinical research, including the University's Center for Clinical and Translational Science, the NIH-funded training program in translational and comparative-effectiveness research and a Pediatric Clinical and Translational Scholars Program. Dr. Hersh currently has 75% protected time which will be ensured throughout the award period to utilize these resources in achieving her career development goals. Research: Dr. Hersh's research proposal incorporates three related research projects focused on describing the long-term outcomes of JIA. Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease; the majority of children with JIA have persistent arthritis into adulthood. JIA is associated with premature morbidities including joint damage, growth impairment, cardiovascular disease and mortality; yet, little is known about the long-term outcomes of this chronic rheumatic disease. The central hypothesis of this proposal is that there are non-modifiable (eg. genetic) and modifiable (eg, treatment, behavioral) risk factors that, if identified, lead to targets for improvd treatment and outcomes for children with JIA. In Aim 1, Dr. Hersh will link the ISDCRD to the UPDB to examine important outcomes of JIA including the incidence of orthopedic procedures, cardiovascular events and malignancy as well as risk of infertility and early mortality. In Aim 2, she will develop a longitudinal cohort of adult patients with JIA to characterize disability and quality of life outcomes for this cohort, as well as predictors for these outcomes. In Aim 3, she will explore the relationship between genetic susceptibility loci and response to treatment in JIA. Preliminary data from this research will be used to develop interventions to improve health outcomes for patients with childhood-onset rheumatic disease. This proposal is designed to facilitate Dr. Hersh's career as an independent investigator devoted to improving care for pediatric patients with a chronic rheumatic disease.