Treatment Approaches and Outcomes in Pouch-related Disorders after Colectomy for Ulcerative Colitis

项目总结 这个以患者为导向的导师研究职业发展奖的总体目标是改善我们的 对修复性回肠直肠切除术后膀胱炎等炎症情况的认识 袋肛门吻合术(IPAA)。巴恩斯博士是诺斯大学积极进取的临床研究人员 在北卡罗来纳州教堂山(北卡罗来纳州大学)，对炎症性肠道疾病的研究特别感兴趣。超过了 在接下来的五年里，巴恩斯博士将与他的指导委员会合作，继续他在 独立的目标。他的指导委员会成员包括胃肠道流行病学专家和 比较有效性(Kappelman)、患者报告的结果[(Pros)DeWalt]和精确医学 (科索沃)。每个成员都有指导初级教员的既定记录，并得到一致的同行评审 支持，以及较高的研究效率。巴恩斯博士的职业发展目标如下：1)发展 使用真实世界数据进行比较有效性研究的新技能；2)获取知识和 开发专业评估的经验；3)获得机器学习和精确度方面的新技能 医学原则，将允许将临床和微生物区系数据纳入新的风险建模 对于接受修复性直肠切除合并IPAA的患者，以及4)过渡到独立。要实现 他的职业发展目标是，巴恩斯博士将参加结构化的课程工作，进行指导 研究，并将参加通过北卡罗来纳州翻译和临床科学的研讨会 研究所，包括R-Writing Group。北卡罗来纳大学的研究和培训环境已经建立起来。为 2019财年，北卡罗来纳大学在全国私立和公立大学中排名第十 卫生研究所(NIH)向国内高等教育机构提供研究资金。这样做的具体目的是 研究项目是1)评估特定生物疗法对 IPAA术后眼袋慢性炎症状态的治疗；2)建立评估指标 IPAA术后患者的生活质量和特定症状领域。PRO开发的技术将 包括使用定性研究方法确定与IPAA后患者相关的症状领域， 在适当的情况下，使用现有的PRO工具选择IPAA特定PRO的候选项目，以及 对IPAA后的患者进行认知访谈，以确保内容有效性；以及3)展示新奇 使用机器学习方法识别慢性膀胱炎预测因子的方法。扩展AN 现有的预期队列，巴恩斯博士将利用粪便微生物组、实验室数据和临床变量来 创建签名以确定慢性膀胱炎的预测因素。良师益友、授课和 通过这项K23计划提供的研究经验将使巴恩斯博士开发出一种独特的技能集， 将有助于他作为临床研究员和研究科学家最终过渡到独立。

PROJECT SUMMARY This overall goal of this mentored patient-oriented research career development award is to improve our understanding of pouchitis and other inflammatory conditions after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). Dr. Barnes is a motivated clinical researcher at the University of North Carolina at Chapel Hill (UNC), with a specific interest in the study of inflammatory bowel diseases. Over the next five years, Dr. Barnes will work with his mentorship committee to continue his progression towards his goal of independence. His mentorship committee includes experts in gastrointestinal epidemiology and comparative effectiveness (Kappelman), patient reported outcomes [(PROs) DeWalt], and precision medicine (Kosorok). Each member has an established track record of mentoring junior faculty, consistent peer-reviewed support, and high research productivity. Dr. Barnes’s career development objectives are as follows: 1) develop a new skillset in comparative effectiveness research using real-world data; 2) obtain knowledge and experience in the development of PRO assessments; 3) acquire new skills in machine learning and precision medicine principles which will allow for the incorporation of clinical and microbiota data into new risk modeling for patients undergoing restorative proctocolectomy with IPAA, and 4) transition to independence. To achieve his career development objectives, Dr. Barnes will participate in structured coursework, conduct mentored research, and will participate in workshops through the North Carolina Translational and Clinical Sciences Institute, including the R-Writing Group. The research and training environment at UNC is well established. For fiscal year 2019, UNC ranked tenth among both private and public universities nationwide for National Institutes of Health (NIH) research funding to domestic institutions of higher education. The specific aims of this research project are 1) to evaluate the comparative effectiveness of specific biologic therapies for the treatment of chronic inflammatory conditions of the pouch after IPAA; 2) to develop PRO items for evaluating quality of life and specific symptom domains among patients after IPAA. Techniques for PRO development will include identifying symptom domains relevant to patients after IPAA using qualitative research methods, selecting candidate items for IPAA-specific PROs using existing PRO instruments where appropriate, and performing cognitive interviews with patients after IPAA to ensure content validity; and 3) to demonstrate novel methods for identifying predictors of chronic pouchitis using a machine learning approach. Expanding an existing prospective cohort, Dr. Barnes will utilize the stool microbiome, laboratory data and clinical variables to create signatures for identifying predictors of chronic pouchitis. The combination of mentorship, didactics, and research experiences offered through this K23 proposal will allow Dr. Barnes to develop a unique skillset that will aid in his ultimate transition to independence as a clinical investigator and research scientist.