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博士是哈佛医学院（HMS）的医学讲师， 马萨诸塞州总医院（MGH）流变学部门的医学助理。后 他在康奈尔大学获得历史学本科学位，在乔治敦大学获得医学博士学位。他 在MGH完成了他的医学住院医师和风湿病学奖学金，在此期间，华莱士博士开始 与Hyon Choi，MD，DrPH一起工作。华莱士博士进行以患者为导向的多系统风湿性关节炎研究 条件，特别是ANCA相关血管炎（AAV），这导致了20个同行评审的原始 论文，10作为第一作者，6在Arthr Rheum和Ann Rheum Dis。 哈佛大学流行病学硕士。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， 导师，培训活动和环境：华莱士博士将在MGH进行拟议的项目 在Hyon Choi，MD，DrPH和John Stone，MD，MPH和罗谢尔的共同指导下 Walensky，MD，MPH. Choi博士是一位世界知名的，NIH资助的高级临床医学科学家。 风湿性疾病的流行病学，范围从常见疾病到罕见但严重的疾病（例如， AAV）。他曾担任过几位K奖获得者的导师。斯通博士是一位临床研究者和专家 他领导了AAV和其他血管炎的里程碑式试验。瓦伦斯基博士是决策专家 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 他的主要合作者的具体专业知识，包括协变量定义算法，血脂分析，生活质量 措施和外部验证。为了补充导师的专业知识，他将获得新的技能 通过先进的临床流行病学，药物流行病学和模拟建模教学。 研究：尽管AAV治疗取得了进展，但它仍然具有4倍的心血管疾病风险 (CVD)，死亡风险高出2倍，与一般情况相比， 人口这项研究的中心目标是通过确定AAV对患者的影响， 关键的潜在预测因素，如ANCA类型和初始治疗选择（利妥昔单抗（RTX）和环， 环磷酰胺（CYC））对CVD风险、死亡率和质量调整生命年（QGR）的影响。为了实现这一目标，他 将在一个大的纵向研究中研究ANCA类型和初始治疗选择对CVD和死亡率的影响， 使用经验证的算法评估电子医疗记录中的协变量的AAV群组（目的1和2）。他将 还研究了RTX和CYC对血脂谱的影响，使用来自随机试验的冷冻样本（目的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Qs 模型（目标3）。完成本建议书和培训计划将使华莱士博士获得重要的经验 成为一名独立的临床研究者，从事以患者为导向的AAV和类似疾病的研究。

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.