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.

项目总结 Pamela Weiss博士在这项提议的支持下，寻求扩大和改进她的研究计划和 她对急需的内科科学家进行的培训、指导和职业发展-- 儿童风湿病的定向研究(POR)。成功的辅导需要有效的被辅导者 和熟练的导师，这两者都反映在此应用程序的培训目标中，并包括构建 具备以下技能：1)培训初级教员和同事建立并有效管理他们的指导关系；2) 教学员如何有效地与他们的指导团队合作，并在研究环境中驾驭。这个 这一应用的前提是利用现有的研究来改善儿童的日常临床护理 它还将帮助设计新出现的靶向治疗方法。三大 障碍阻碍了青少年脊柱炎护理的进步。首先，在解释上存在差异 诊断影像研究，因为区分未成熟的结构骨和软骨下骨髓 儿童骶骨关节的浮肿是具有挑战性的。来自扩散的表观扩散系数(ADC)- 加权成像(DWI)为儿科人群提供了独特的希望，将其作为区分成熟性别的工具。 病理性炎症引起的变化。其次，目前尚无儿科诊断标准。 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 设置以准确识别那些将从临床试验中受益的人。第三，虽然有一个青少年 在临床研究中广泛使用的脊柱关节炎疾病活动度(JSpADA)指数，其临界值为 定义临床上重要的疾病状态是未知的。由于非活动性疾病对许多人来说仍然遥不可及 对于幼年型脊柱炎，迫切需要确定临床上最小的重要改善。 (MCII)和明确定义的疾病活动状态，使用JSpADA索引，不仅用于临床护理，而且用于 还有对新兴疗法的研究。拟议的研究解决了这些挑战，并利用现有的 应聘者在世界知名的儿科三级护理中心进行的研究 脊椎炎和创新成像。AIM 1将测试来自DWI的ADC作为诊断生物标志物 儿童中存在的骶髂炎。目标2将确定基于病变的候选标准来定义阳性 骶骨关节核磁共振。目标3将确定定义最低疾病活跃度的MCII和分界值 JSpADA指数的疾病活跃度较高。这些目标将同时为 正在进行的研究，帮助申请者发展新的研究和指导技能，并提供临床研究 指导POR的年轻内科科学家并促进他们向独立过渡的平台。