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

ANCA 类型和利妥昔单抗与环磷酰胺对 ANCA 相关性血管炎的心血管风险、死亡率和质量调整生命年的影响

• 批准号: 9886161
• 负责人: Zachary Scott Wallace
• 金额: $ 17.84万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9886161
• 关键词: Address; Affect; Algorithms; Antineutrophil Cytoplasmic Antibodies; Apolipoproteins B; Bachelor' s Degree; Blood Vessels; Blood specimen; Cardiovascular Diseases; Caring; Cessation of life; Classification; Clinical; Clinical Investigator; Complement; Computerized Medical Record; Cost Effectiveness Analysis; Cyclophosphamide; Data; Data Sources; Disease; Disease remission; Endothelium; Environment; Epidemiology; Fellowship; Flare; Foundations; Freezing; Funding; Future; General Hospitals; General Population; Genetic; Glucocorticoids; Goals; Grant; High Density Lipoprotein Cholesterol; Impairment; Infection; Inflammation; K-Series Research Career Programs; Kidney; Kidney Diseases; Knowledge; Lead; Life Expectancy; Lipids; Literature; Lung; Maintenance; Massachusetts; Master of Science; Mathematical Model Simulation; Measures; Mediating; Mediation; Medicine; Mentors; Mentorship; Methodology; Methods; Modeling; Monte Carlo Method; Neoadjuvant Therapy; Organ; Outcome; PRTN3 gene; Paper; Pathogenesis; Pathology; Patients; Peer Review; Pharmacoepidemiology; Physicians; Positioning Attribute; Quality of life; Quality-Adjusted Life Years; Randomized; Randomized Controlled Trials; Recommendation; Recording of previous events; Remission Induction; Research; Research Personnel; Residencies; Rheumatoid Arthritis; Rheumatology; Rhubarb food; Risk; Risk Factors; Role; Running; SF-36; Sampling; Science; Scientist; Scoring Method; Subgroup; Survival Analysis; Training; Training Activity; Translating; United States National Institutes of Health; Universities; Validation; Vasculitis; arm; base; cardiovascular disorder risk; cardiovascular risk factor; clinical epidemiology; cohort; comparative effectiveness; evidence base; expectation; experience; high risk; improved; instructor; markov model; medical schools; models and simulation; mortality; mortality risk; patient oriented; patient oriented research; randomized trial; rituximab; simulation; skills; treatment choice; treatment response; treatment strategy

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.

候选人：扎卡里·S·华莱士 (Zachary S. Wallace) 医学博士是哈佛医学院 (HMS) 的医学讲师和 马萨诸塞州总医院 (MGH) 风湿病科医学助理。在他之后 他在康奈尔大学获得历史学学士学位，在乔治城大学获得医学博士学位。他 华莱士博士在麻省总医院完成了医学住院医师培训和风湿病学研究金，在此期间，华莱士博士开始了 与 Hyon Choi（医学博士、公共卫生博士）合作。 Wallace博士进行以患者为中心的多系统风湿病研究 条件，特别是 ANCA 相关血管炎 (AAV)，这导致了 20 项经过同行评审的原始研究 其中第一作者论文 10 篇，Arthr Rheum 和 Ann Rheum Dis 论文 6 篇。华莱士博士即将完成他的 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 以及以患者为导向的 AAV 和多系统风湿病研究领域的世界级领导者。 指导、培训活动和环境：华莱士博士将在麻省总医院开展拟议项目 在 Hyon Choi（医学博士、公共卫生博士）的指导下以及 John Stone（医学博士、公共卫生硕士）和 Rochelle 的共同指导下 瓦伦斯基，医学博士，公共卫生硕士。 Choi 博士是世界知名的高级临床医学科学家，获得 NIH 资助 风湿病的流行病学，从常见疾病到罕见但严重的疾病（例如， 腺病毒）。他曾担任过几位 K 获奖者的导师。 Stone 博士是一名临床研究者和专家 在 AAV 领域，他领导了 AAV 和其他血管炎的里程碑式试验。 Walensky 博士是决策专家 科学、仿真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、脂质分析、生活质量 措施和外部验证。为了补充导师的专业知识，他将获得新技能 通过高级临床流行病学、药物流行病学和模拟建模的教学。 研究：尽管 AAV 护理取得了进步，但其患心血管疾病的风险仍然高出 4 倍 (CVD)，与一般人相比，死亡风险高出 2 倍，并且生活质量显着受损 人口。这项研究的中心目标是通过确定 AAV 的影响来改善长期 AAV 结果 关键潜在预测因素，例如 ANCA 类型和初始治疗选择（利妥昔单抗 (RTX) 和环 磷酰胺（CYC））对CVD风险、死亡率和质量调整生命年（QALY）的影响。为了实现这个目标，他 将在大型纵向研究中检查 ANCA 类型和初始治疗选择对 CVD 和死亡率的影响 AAV 队列使用经过验证的算法来评估电子病历中的协变量（目标 1 和 2）。他会 还使用随机试验的冷冻样本研究 RTX 和 CYC 对血脂谱的影响（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）。完成此提案和培训计划将使华莱士博士获得重要的经验 成为以患者为导向的 AAV 和类似疾病研究的独立临床研究者。