UGI HEMORRHAGE AND BARRETTS EPITHELIUM

我与这一奖项相关的主要职业目标是：1)在消化系统疾病专业领域追求一个由研究人员发起、假设驱动、高质量以患者为导向的研究计划；2)指导几乎没有研究经验的年轻临床医生以患者为导向的职业发展；以及3)继续指导其他临床研究人员，并与他们合作，这些研究人员超出了临床研究人员的入门水平。美国国立卫生研究院的两项研究和几项新的合作研究支持这项研究和指导建议。美国国立卫生研究院的第一项拨款“UGI出血和内窥镜止血研究”评估了因消化性溃疡、Dieulafoy病变或Mallory Weiss泪水引起的严重上消化道出血(UGIB)患者。在三个连续的多中心随机双盲试验中，我们的假设是，联合治疗(肾上腺素和凝血)在初始止血、降低早期再出血率和降低医院护理费用方面将显著优于热疗。美国国立卫生研究院的第二项拨款“通过根除幽门螺杆菌预防溃疡出血”是一项多中心、双盲、随机比较两种不同药物治疗方法以防止十二指肠溃疡(DU)和胃溃疡(GU)出血复发的研究。要测试的总体假设是：1)仅根除幽门螺杆菌(H.Pylori)感染就可以治愈大多数慢性消化性溃疡患者，在预防复发溃疡出血方面基本上相当于根除Hp+全量维持H2 RA；2)长期随访期间，服用阿司匹林或其他非类固醇抗炎药或Hp感染复发将导致溃疡出血的所有复发。还提出了巴雷特上皮的新合作研究，以及静脉曲张和非静脉曲张出血的前瞻性试验。在指导计划中，新的研究人员将接受培训，以执行随机前瞻性试验、内窥镜技术评估研究和以患者为导向的研究。这种指导将被生物统计学的教学课程、研究设计的研讨会和其他关于数据管理、前瞻性试验的表格设计和方案编写的指导相补充。重点将放在计划、设计和进行实际的前瞻性随机研究上。这一奖项将提高申请者的研究生产力，并为年轻研究人员提供熟练的指导，使他们能够成为消化系统疾病方面独立的、以患者为中心的研究人员。

My primary career goals related to this award are: 1) to pursue a program of investigator-initiated, hypothesis driven, high quality patient-oriented research in the specialty of digestive diseases, 2) to mentor young clinicians, with little or no research experience, in their career development as patient-oriented researchers, and 3) to continue to mentor and collaborate with other clinical researchers who are beyond the entry level as clinical investigators. Two NIH studies and several new collaborative studies support this research and mentoring proposal. The first NIH Grant, "Studies of UGI Hemorrhage and Endoscopic Hemostasis" evaluates patients with severe upper gastrointestinal bleeding (UGIB) from peptic ulcers, Dieulafoy's lesions, or Mallory Weiss tears. In three consecutive blinded, multicenter randomized trials, our hypothesis is that combination therapy (epinephrine and coagulation) will be significantly better than thermal therapy for initial hemostasis, reduction in early rebleeding rates, and reduction in hospital costs of care. The second NIH Grant, "Prevention of Ulcer Hemorrhage by H.pylori Eradication" is a multicenter, double-blind, randomized comparison of two different medical treatments to prevent recurrence of duodenal ulcer (DU) and gastric ulcer (GU) bleeding. The overall hypotheses to be tested are that 1) eradication of Helicobacter pylori (H. pylori) infection alone will cure most patients of their chronic peptic ulcers and will be substantially equivalent to H.pylori eradication plus full-dose H2RA maintenance in preventing recurrent ulcer hemorrhage and 2) ingestion of aspirin or other non-steroidal anti-inflammatory drugs or recurrence of H.pylori infection will account for all recurrences of ulcer hemorrhage during long-term follow-up. New collaborative studies are also proposed of Barrett's epithelium and prospective trials of variceal and non-variceal hemorrhage. In the mentoring program, new investigators will be trained to perform randomized prospective trials, endoscopic technology assessment studies, and patient-oriented research. This mentoring will be supplemented by didactic courses in biostatistics, seminars in study design, and other instruction in data management, form design for prospective trials, and protocol writing. Emphasis will be placed on planning, designing, and conducting actual prospective randomized studies. This award will enhance the applicant's research productivity and provide skilled mentoring for young investigators, so they can become independent patient-oriented investigators in digestive diseases.