Investigating strategies to reduce fluid-related complications among hemodialysis patients

研究减少血液透析患者液体相关并发症的策略

• 批准号: 9507849
• 负责人: Jennifer E Flythe
• 金额: $ 19.81万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9507849
• 关键词: Achievement; Advisory Committees; Anuria; Award; Biometry; Blood Pressure; Blood Vessels; Cardiac; Cardiovascular system; Chronic; Clinical; Clinical Research; Clinical Trials; Clinical and Translational Science Awards; Cross-Over Studies; Data; Databases; Development; Development Plans; Dialysis patients; Dialysis procedure; Diuretics; Doctor of Philosophy; Double-Blind Method; Echocardiography; Educational workshop; Elderly; Environment; Epidemiologic Methods; Epidemiology; Excision; Excretory function; Failure; Fluid Balance; Fluid overload; Funding; Future; Gills; Goals; Health Care Costs; Health Services Research; Hemodialysis; Home environment; Hospitalization; Hydration status; Hypotension; Intake; Intervention Studies; K-Series Research Career Programs; Kidney; Leadership; Liquid substance; Maintenance; Medicare; Medicine; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Morbidity - disease rate; Myocardial Ischemia; Myocardial Stunning; Nephrology; North Carolina; Organ; Outcome; Outcomes Research; Outpatients; Output; Pathway interactions; Patient Preferences; Patient Selection; Patients; Pennsylvania; Pharmaceutical Preparations; Pharmacoepidemiology; Pharmacologic Substance; Pharmacotherapy; Physician Executives; Process; Productivity; Provider; Public Health; Randomized; Recording of previous events; Reflex action; Regimen; Renal function; Research; Research Personnel; Residual state; Resources; Risk; Risk Reduction; Role; Schools; Series; Sodium; Techniques; Time; Training; Troponin T; Ultrafiltration; United States; Universities; Urine; Weight; Weight Gain; Work; adverse outcome; base; cardiovascular risk factor; career development; cohort; comparative; comparative effectiveness; design; dietary restriction; effectiveness research; epidemiology study; experience; health economics; health related quality of life; hemodynamics; improved; improved outcome; indexing; innovation; medical schools; mid-career faculty; mortality; patient oriented; patient population; pressure; professor; risk mitigation; skills; treatment strategy; ventricular hypertrophy

PROJECT SUMMARY/ ABSTRACT The purpose of this K23 Mentored Career Development Award proposal is to provide Jennifer E. Flythe, MD, MPH with the protected time and resources to allow her to pursue the additional training needed to reach her long-term goal of becoming an independent patient-oriented investigator. Dr. Flythe is a board-certified nephrologist at the University of North Carolina (UNC) at Chapel Hill. Her research focuses on fluid management among maintenance hemodialysis (HD) patients. Dialysis patients experience exceedingly high rates of cardiovascular complications that contribute to both poor health-related quality of life and high healthcare costs. Fluid-related factors are critical contributors to these adverse outcomes. Greater fluid gain between treatments obligates faster fluid removal (ultrafiltration, UF) during dialysis. Rapid UF rates are associated with intradialytic hypotension, chronic volume expansion due to reactive fluid boluses and failure to achieve target weight, and other adverse clinical outcomes. Innovative and patient-acceptable approaches to reducing UF-related harm are needed to improve outcomes. The support of the K23 Award will allow Dr Flythe to achieve the following objectives: 1) investigate the comparative cardiovascular risks of diuretic cessation (versus continuation) among patients initiating HD; 2) investigate the comparative effectiveness of UF profiling vs. conventional dialysis in reducing cardiovascular- related HD complications; 3) gain new epidemiology and clinical trials research skills; and 4) acquire expertise in cardiovascular outcomes. To accomplish these objectives, Dr. Flythe will investigate the comparative risks of diuretic cessation (vs. continuation) after HD initiation in a cohort of incident HD patients with histories of pre- dialysis diuretic use (Aim 1). Second, she will perform a crossover study of 30 maintenance HD patients with histories of elevated UF rates to investigate whether UF profiling vs. conventional HD reduces hypotension and cardiac ischemia (Aim 2). Additionally, she will complete formal coursework in advanced epidemiology and clinical trials and participate in targeted workshops and seminar series to broaden her comparative effectiveness research skillset. She will leverage a unique dialysis cohort of merged large dialysis organization and Medicare administrative claims data as well as UNC-owned outpatient dialysis facilities to accomplish these aims. The proposed work has high potential to make a significant clinical impact, as completion of the project aims will not only advance the current understanding of strategies to reduce UF-related harm but also provide preliminary data on strategies to target in future, larger trials. Importantly, the proposed work is realistic and feasible within the award period and will allow Dr. Flythe to build research skills, generate preliminary data, create collaborative relationships, and compete for R01 funding. Dr. Flythe will be closely guided by her co-primary mentors, M. Alan Brookhart, PhD, Professor of Epidemiology at the UNC Gillings School of Global Public Health, and Ronald J. Falk, MD, Professor of Medicine at the UNC School of Medicine. Doctors Brookhart and Falk’s complementary strengths in epidemiology and biostatistics (Brookhart) and national nephrology leadership (Falk) will be augmented by Dr. Flythe’s scientific advisory committee: 1) Alan Hinderliter, MD, Associate Professor of Medicine at UNC, cardiologist and echocardiography and cardiovascular outcomes expert; 2) Steven M. Brunelli, MD, MSCE, Vice President and Medical Director of Health Economics and Outcomes Research at DaVita Clinical Research and expert in dialysis outcomes research and HD hemodynamics; and 3) Laura Dember, MD, Professor of Medicine at the University of Pennsylvania Perelman School of Medicine and dialysis clinical trial expert. Dr. Flythe will also draw upon the wealth of resources available in UNC’s research environment that include the UNC Schools of Medicine and Public Health, UNC Kidney Center, NC TraCS (home to UNC’s Clinical and Translational Science Award), Cecil G. Sheps Center for Health Services Research, and the UNC- owned Carolina dialysis units. Dr. Flythe’s proposed K23 research aims, mentorship team, career development plan, and collaborative research environment will catalyze her scientific productivity and provide her with the necessary skills and experience in epidemiology and clinical trials to become an independent investigator and future leader in dialysis research.

项目概要/摘要 K23 指导职业发展奖提案的目的是为 Jennifer E. Flythe 提供： MD、MPH 拥有受保护的时间和资源，使她能够接受达到目标所需的额外培训 她的长期目标是成为一名独立的以患者为导向的研究者。 Flythe 博士是经过董事会认证的 北卡罗来纳大学教堂山分校 (UNC) 的肾脏病学家。她的研究重点是流体 维持性血液透析（HD）患者的管理。透析患者的体验非常高 心血管并发症的发生率导致健康相关的生活质量差和高 医疗费用。液体相关因素是导致这些不良后果的关键因素。更大的液体增益 治疗之间需要在透析过程中更快地去除液体（超滤，UF）。快速超滤率是 与透析中低血压、反应性液体推注导致的慢性容量扩张以及未能 达到目标体重和其他不良临床结果。创新且患者可接受的方法 需要减少与超滤相关的危害以改善结果。 K23 奖的支持将使 Flythe 博士实现以下目标：1）调查 开始 HD 的患者中停止利尿剂（与继续使用利尿剂）的心血管风险的比较； 2） 研究超滤分析与传统透析在减少心血管疾病方面的比较效果 相关 HD 并发症； 3）获得新的流行病学和临床试验研究技能； 4）获得专业知识 心血管结局。为了实现这些目标，Flythe 博士将调查以下各项的比较风险： 在一组有 HD 病史的突发 HD 患者中，开始 HD 后停止利尿剂（与继续使用） 透析利尿剂的使用（目标 1）。其次，她将对 30 名患有以下疾病的维持性 HD 患者进行交叉研究： UF 率升高的历史，以研究 UF 分析与传统 HD 相比是否可以降低低血压和 心脏缺血（目标 2）。此外，她还将完成高级流行病学和 临床试验并参加有针对性的研讨会和研讨会系列，以扩大她的比较范围 有效性研究技能。她将利用合并后的大型透析组织的独特透析队列 和医疗保险行政索赔数据以及北卡罗来纳大学拥有的门诊透析设施来完成 这些目标。随着这项工作的完成，拟议的工作很有可能产生重大的临床影响 项目目标不仅将增进目前对减少UF相关危害的战略的理解，而且 提供有关未来更大规模试验目标策略的初步数据。重要的是，拟议的工作是现实的 并且在奖励期内可行，并且将使 Flythe 博士能够培养研究技能，生成初步数据， 建立合作关系，并争夺 R01 资金。 Flythe 博士将受到她的共同主要导师、M. Alan Brookhart 博士、教授的密切指导。 北卡罗来纳大学吉林斯全球公共卫生学院流行病学教授 Ronald J. Falk 医学博士 北卡罗来纳大学医学院的医学。布鲁克哈特医生和福尔克医生在以下方面的优势互补 流行病学和生物统计学（Brookhart）以及国家肾脏病学领导（Falk）将由 Dr. Flythe 的科学顾问委员会：1) Alan Hinderliter，医学博士，北卡罗来纳大学医学副教授， 心脏病专家、超声心动图和心血管结果专家； 2) 史蒂文·M·布鲁内利（Steven M. Brunelli），医学博士，理学硕士， DaVita Clinical 健康经济学和结果研究副总裁兼医学总监 透析结果研究和HD血流动力学研究和专家； 3）劳拉·登伯（Laura Dember）医学博士， 宾夕法尼亚大学佩雷​​尔曼医学院医学教授及透析临床试验 专家。 Flythe 博士还将利用北卡罗来纳大学研究环境中的丰富资源， 包括北卡罗来纳大学医学院和公共卫生学院、北卡罗来纳大学肾脏中心、北卡罗来纳大学 TraCS（北卡罗来纳大学 临床和转化科学奖）、塞西尔·谢普斯卫生服务研究中心和北卡罗来纳大学 拥有卡罗莱纳州透析单位。 Flythe博士提出的K23研究目标、导师团队、职业发展 计划和协作研究环境将促进她的科学生产力并为她提供 成为独立研究者所需的流行病学和临床试验技能和经验 透析研究的未来领导者。