Impact of ANCA Type and Rituximab vs. Cyclophosphamide on Cardiovascular Risk, Mortality, and Quality-Adjusted Life Years inANCA-Associated Vasculitis

候选人：Zachary S.Wallace，医学博士，哈佛医学院(HMS)医学讲师 马萨诸塞州综合医院风湿科的医学助理。在他的 他在康奈尔大学获得历史学学士学位，在乔治敦大学获得医学博士学位。他 完成了他在麻省理工学院的医学实习和风湿病研究，在此期间，华莱士博士开始 与Hyon Choi，医学博士，DrPH合作。华莱士博士进行以患者为导向的多系统风湿病研究 病情，特别是ANCA相关性脉管炎(AAV)，已导致20个同行审查的原始 第一作者10篇，《大黄》和《安大黄》6篇。华莱士医生正在完成他的 哈佛大学流行病学理学硕士。他的目标是成为一名独立调查员 在以患者为导向的AAV和多系统风湿性疾病研究方面处于世界领先地位。 指导、培训活动和环境：华莱士博士将在麻省理工学院主持拟议的项目 在Hyon Choi，MD，DrPH的指导下，以及John Stone，MD，公共卫生硕士和Rochelle的共同指导下 沃伦斯基，医学博士，最高时速。崔医生是美国国立卫生研究院资助的高级临床领域的世界知名内科科学家。 风湿病的流行病学，从常见的疾病到罕见但严重的疾病(例如， AAV)。他已经断绝了之前几位K奖获得者的导师身份。斯通博士是一名临床研究员和专家。 在AAV中，世卫组织领导了AAV和其他脉管炎的里程碑式试验。瓦伦斯基博士是一位决策专家 科学、模拟建模和成本效益分析。华莱士博士的研究也将受益于 他的主要合作者的特定专业知识，包括协变量定义算法、血脂分析、生活质量 测量和外部验证。为了补充他导师的专业知识，他将获得新的技能 通过讲授高级临床流行病学、药物流行病学和模拟建模。 研究：尽管AAV护理取得了进步，但患心血管疾病的风险仍高出4倍 (CVD)，死亡风险是普通患者的2倍，生活质量显著下降 人口。这项研究的中心目标是通过确定影响改善AAV的长期结果 关键的潜在预测因素，如ANCA类型和初步治疗选择(美罗华(RTX)和环磷酰胺- 对心血管疾病风险、死亡率和质量调整寿命年(QALY)的影响。为了实现这一目标，他 将研究ANCA类型和初始治疗选择对心血管疾病和死亡率的影响 使用经过验证的算法评估电子病历中的协变量的AAV队列(目标1和2)。他会的 同时使用随机试验的冷冻样本来研究RTX和CyC对血脂的影响(目标2)。 最后，他将在模拟中预测与初始诱导治疗选择和ANCA类型相关的QALY 模型(目标3)。该提案和培训计划的完成将使华莱士博士获得至关重要的经验 成为AAV和类似情况下以患者为导向的研究的独立临床研究员。

Candidate: Zachary S. Wallace, MD is an Instructor in Medicine at Harvard Medical School (HMS) and an Assistant in Medicine in the Rheumatology Unit at Massachusetts General Hospital (MGH). After his undergraduate degree in History from Cornell University, he received his MD at Georgetown University. He completed his medicine residency and rheumatology fellowship at MGH, during which Dr. Wallace began working with Hyon Choi, MD, DrPH. Dr. Wallace conducts patient-oriented research of multi-system rheumatic conditions, especially ANCA-associated vasculitis (AAV), which has resulted in 20 peer-reviewed original papers, with 10 as the first author and 6 in Arthr Rheum and Ann Rheum Dis. Dr. Wallace is completing his Master of Science in Epidemiology at Harvard University. His goal is to become an independent investigator and world-class leader in patient-oriented research of AAV and multi-system rheumatic conditions. Mentorship, Training Activities, and Environment: Dr. Wallace will conduct the proposed project at MGH under the mentorship of Hyon Choi, MD, DrPH and co-mentorship of John Stone, MD, MPH and Rochelle Walensky, MD, MPH. Dr. Choi is a world-renowned, NIH-funded physician scientist in advanced clinical epidemiology of rheumatic conditions, ranging from common disorders to rare but serious disorders (e.g., AAV). He has severed as a mentor for several prior K awardees. Dr. Stone is a clinical investigator and expert in AAV who has led landmark trials in AAV and other vasculitides. Dr. Walensky is an expert in decision science, simulation modeling, and cost-effectiveness analysis. Dr. Wallace' research will also benefit from the specific expertise of his key collaborators, including covariate definition algorithms, lipid analysis, quality of life measures, and external validation. To complement the expertise of his mentors, he will acquire new skills through didactics on advanced clinical epidemiology, pharmacoepidemiology, and simulation modeling. Research: Despite advances in AAV care, it continues to carry a 4-fold higher risk of cardiovascular disease (CVD), a 2-fold higher risk of death, and a significant quality-of-life impairment compared to the general population. The central goal of this research is to improve long-term AAV outcomes by determining the impact of key potential predictors such as ANCA types and initial treatment choice (rituximab (RTX) & cyclo- phosphamide (CYC)) on CVD risk, mortality, and quality-adjusted life years (QALYs). To achieve this goal, he will examine the impact of ANCA type and initial treatment choice on CVD and mortality in a large longitudinal AAV cohort using validated algorithms to assess covariates in electronic medical records (Aims 1& 2). He will also study the effect of RTX and CYC on lipid profiles using frozen samples from a randomized trial (Aim 2). Finally, he will project QALYs associated with initial induction therapy choice and ANCA type in a simulation model (Aim 3). Completion of this proposal and training plan will position Dr. Wallace with the vital experience to become an independent clinical investigator in patient-oriented research of AAV and similar conditions.