Mentoring and Patient Oriented Research in Juvenile Spondyloarthritis

青少年脊柱关节炎的指导和以患者为导向的研究

• 批准号: 10370698
• 负责人: Pamela Fitch Weiss
• 金额: $ 13.27万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10370698
• 关键词: Accounting; Address; Adolescent; Adult; Advisory Committees; Anatomy; Ankylosing spondylitis; Arthritis; Bone Marrow; Caring; Child; Child Care; Childhood; Chronic Childhood Arthritis; Classification; Clinical; Clinical Research; Clinical Trials; Data; Data Sources; Diagnostic Imaging; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Disease remission; Early Diagnosis; Edema; Ensure; Environment; Faculty; Funding; Goals; Image; Image Analysis; Imaging Techniques; Inflammation; Inflammatory; Interleukin-17; International; Joints; Lesion; Location; Magnetic Resonance Imaging; Mentors; Methodology; NIH Program Announcements; Outcome; Pathologic; Pathology; Pathway interactions; Pelvis; Physicians; Population; Predictive Value; Public Health; Recommendation; Research; Research Methodology; Research Personnel; Rheumatology; Risk; Sacroiliac joint structure; Scientist; Societies; Specificity; Spondylarthritis; Suggestion; Techniques; Testing; Time; Training; Work; base; career development; clinical care; design; diagnostic accuracy; diagnostic biomarker; effectiveness study; efficacy study; epidemiology study; experience; functional disability; imaging biomarker; imaging study; improved; indexing; inhibitor; innovation; interleukin-23; next generation; novel; patient oriented research; peer; prevent; programs; quantitative imaging; rheumatologist; skills; subchondral bone; success; targeted treatment; tertiary care; tool

PROJECT SUMMARY Dr. Pamela Weiss, with the support of this proposal, seeks to expand and improve her research program and her training, mentoring, and career development of greatly needed physician scientists pursuing patient- oriented research (POR) in pediatric rheumatology. Successful mentoring requires both an effective mentee and a skilled mentor, both of which are reflected in the training goals of this application and include building skills to 1) train junior faculty and peers to build and effectively manage their mentoring relationships, and 2) teach trainees how to effectively work with their mentoring team and navigate the research environment. The premise of this application is to leverage existing studies to improve the everyday clinical care of children with spondyloarthritis and to contribute to the design of studies of emerging targeted therapies. Three major obstacles block advancements in juvenile spondyloarthritis care. First, there is variability in the interpretation of diagnostic imaging studies because distinguishing immature structural bone from subchondral bone marrow edema at the sacroiliac joints in children is challenging. The apparent diffusion coefficient (ADC) from diffusion- weighted imaging (DWI) holds unique promise for the pediatric population as a tool to distinguish maturational changes from pathologic inflammation. Second, there are no pediatric diagnostic imaging criteria for sacroiliitis. Improved criteria is needed not only in the clinical setting to prevent overdiagnosis, but also in the research setting to accurately identify those who would benefit from clinical trials. Third, although there is a juvenile spondyloarthritis disease activity (JSpADA) index that is widely used in clinical research, the cut-off values for defining clinically important disease states are unknown. Since inactive disease remains unattainable for many with juvenile spondyloarthritis, there is a critical need to determine minimal clinically important improvement (MCII) and well-defined states of disease activity using the JSpADA index for use not only in clinical care but also studies of emerging therapies. The proposed research addresses these challenges and leverages existing studies conducted by the candidate at a world-renowned pediatric tertiary care center with expertise in spondyloarthritis and innovative imaging. Aim 1 will test ADC from DWI as a diagnostic biomarker for the presence of sacroiliitis in children. Aim 2 will determine candidate lesion-based criteria for defining a positive sacroiliac joint MRI. Aim 3 will determine the MCII and cut-off values for defining minimal disease activity and high disease activity for the JSpADA index. These aims will simultaneously provide significant added value to ongoing studies, aid the applicant to develop new research and mentoring skills, and offer a clinical research platform in which to mentor young physician scientists in POR and promote their transition to independence.

项目摘要 博士帕梅拉韦斯，与支持这一建议，寻求扩大和改善她的研究计划， 她的培训，指导，和职业发展的迫切需要的医生科学家追求病人， 小儿风湿病学的定向研究（POR）。成功的辅导需要有效的学员 和一个熟练的导师，这两个都反映在本申请的培训目标，包括建立 技能1）培训初级教师和同行建立和有效地管理他们的指导关系，以及2） 教导学员如何有效地与他们的指导团队合作，并浏览研究环境。的 本申请的前提是利用现有的研究，以改善儿童的日常临床护理 脊柱关节炎，并有助于新兴的靶向治疗研究的设计。三大 阻碍青少年脊柱关节炎治疗进展的障碍。第一，在解释上存在差异， 诊断成像研究，因为区分未成熟的结构骨和软骨下骨髓 儿童骶髂关节处的水肿是具有挑战性的。表观扩散系数（ADC）从扩散- 磁共振加权成像（DWI）作为一种区分成熟期和非成熟期的工具， 病理性炎症的变化。其次，骶髂关节炎没有儿科影像学诊断标准。 不仅在临床环境中需要改进标准以防止过度诊断，而且在研究中也需要改进标准。 以准确识别那些将从临床试验中受益的人。第三，虽然有一个少年 脊柱关节炎疾病活动度（JSpADA）指数广泛用于临床研究， 定义临床重要疾病状态是未知的。由于非活动性疾病对许多人来说仍然无法实现， 对于幼年脊柱关节炎，迫切需要确定最小的临床重要改善 （MCII）和使用JSpADA指数的明确定义的疾病活动状态，不仅用于临床护理， 也是新兴疗法的研究拟议的研究解决了这些挑战，并利用现有的 由候选人在世界知名的儿科三级护理中心进行的研究， 脊柱关节炎和创新成像。目标1将测试DWI的ADC作为诊断生物标志物， 儿童骶髂关节炎。目标2将确定用于定义阳性的基于病变的候选标准。 骶髂关节MRI。目标3将确定MCII和临界值，用于定义最小疾病活动性， JSpADA指数的高疾病活动性。这些目标将同时为 正在进行的研究，帮助申请人发展新的研究和指导技能，并提供临床研究 在这个平台上，指导POR的年轻医生科学家，并促进他们向独立过渡。