AGING AND THE HUMAN ANTIBODY RESPONSE TO C. DIFFICILE

申请者Lorraine Kyne，医学博士，公共卫生硕士，将在贝丝以色列女执事医学中心(BIDMC)老年病学部进行一项研究计划。该奖项将提供五年的指导培训和研究，使她能够发展自己的潜力，成为一名专注于以患者为中心的研究的独立临床调查员。BIDMC老年科主任、哈佛医学院老年科主任Jeanne Y.魏博士和BIDMC消化科副医生Ciaran P.Kelly博士将担任导师。研究部分将侧重于影响主要老年患者的一种重要的医源性医院条件：艰难梭菌相关性疾病(CDAD)。由于这种疾病的常规抗生素治疗与高复发率和出现抗菌素耐药性有关，该项目的长期目标是开发免疫生物学产品来预防或改善艰难梭菌引起的疾病，并在干预研究中测试其在‘高危’老年人中的有效性。该项目的具体目标是：1)确定针对严重、长期或复发的艰难梭菌腹泻的免疫保护的替代标记物，以用于未来的艰难梭菌主动或被动免疫试验；2)探索艰难梭菌、艰难梭菌引起的疾病的免疫反应与年龄之间的相互关系；以及3)确定CDAD的临床相关性，以开发临床预测规则，用于识别可能受益于免疫或其他预防策略的高危个体。除了这个项目以及与魏博士和凯利博士的预定会面之外，该奖项还将包括一个正式的研究课程，包括1)研究伦理学、2)临床流行病学、3)统计分析、4)临床试验、5)衰老研究和5)实验室技术。哈佛老年学部和BIDMC老年学和胃肠病学部将为申请者提供非常丰富的研究、教育和临床资源，以确保成功实现该奖项的目标。

A research program will be undertaken by the applicant, Lorraine Kyne, MD, MPH in the Division of Gerontology at the Beth Israel Deaconess Medical Center (BIDMC). The award will provide five years of mentored training and research enabling her to develop her potential to become an independent clinical investigator focusing on patient-oriented research. Dr Jeanne Y. Wei, Chief of Gerontology at BIDMC, Director of the Division on Aging at Harvard Medical School and Dr. Ciaran P. Kelly, Associate Physician in the Division of Gastroenterology, BIDMC, will serve as mentors. The research component will focus on an important iatrogenic, nosocomial condition which affects predominantly older patients: Clostridium difficile-associated disease (CDAD). As the conventional antibiotic therapy of this condition is associated with a high relapse rate and the emergence of antimicrobial resistance, the long term goals of this project are to develop immunobiological products to prevent or ameliorate disease due to C. difficile and to test their efficacy in intervention studies in 'high risk' older persons. The specific aims of this project are; 1) to identify surrogate markers of immune protection against severe, prolonged or recurrent C. difficile diarrhea for use in future C. difficile active or passive immunization trials; 2) to explore the inter- relationship between the immune response to C. difficile, disease due to C. difficile and aging; and 3) to determine the clinical correlates of CDAD, in order to develop a clinical prediction rule which may be used to identify high risk individuals who may benefit from immunization or other preventative strategies. In addition to this project and scheduled meetings with Drs. Wei and Kelly, this award will include a formal research curriculum, including 1) Research ethics, 2) Clinical epidemiology, 3) Statistical analysis, 4) Clinical trials, 5) Aging research and 5) Laboratory techniques. The very substantial research, educational, and clinical resources of the Harvard Division on Aging and the BIDMC Gerontology and Gastroenterology Divisions will be committed to the applicant to ensure successful attainment of the goals of this award.