Exploring the Biomechanics of Joint Bleeding in Persons with Hemophilia to Better

更好地探索血友病患者关节出血的生物力学

• 批准号: 10356156
• 负责人: Beth Boulden Warren
• 金额: $ 18.83万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-19 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10356156
• 关键词: Acceleration; Ankle; Biomechanics; Biomedical Engineering; Blood; Blood Coagulation Disorders; Blood Coagulation Factor; Blood coagulation; Clinical Research; Collection; Colorado; Data; Data Analyses; Dose; Dyskinetic syndrome; Event; F8 gene; Factor IX; Factor VIII; Faculty; Financial Hardship; Frequencies; Future; Gills; Goals; Gold; Health; Hematology; Hemophilia A; Hemophilic Arthritis; Hemorrhage; Hemostatic Agents; Infrastructure; Inherited; Injections; Interruption; Intravenous; Joints; Knee; Knowledge; Lead; Leg; Life; Linear Regressions; Lower Extremity; Measurement; Measures; Mental Health; Mentored Patient-Oriented Research Career Development Award; Mentors; Methods; Modeling; Motion; Movement; Muscle; Outcome; Participant; Pattern; Persons; Pharmaceutical Preparations; Physical activity; Physical therapy; Prevention; Prophylactic treatment; Prospective cohort; Regimen; Regression Analysis; Research; Research Personnel; Research Training; Risk; Risk Factors; Rotation; Running; Science; Scientist; Secure; Severities; Signal Transduction; Social Functioning; Statistical Models; Stress; Techniques; Technology; Testing; Therapeutic Intervention; Thrombosis; Time; Tissues; Training; Universities; Variant; Walking; Weight; arthropathies; base; career; career development; cohort; cost; experience; improved; joint biomechanics; joint injury; joint loading; member; movement analysis; novel strategies; obesity prevention; patient oriented; predictive modeling; prevent; prophylactic; prospective; research and development; signal processing; skills; smartphone Application; tool; wearable device

PROJECT SUMMARY/ABSTRACT Hemophilia is an inherited deficiency of clotting factor VIII or IX, which causes joint bleeding and crippling arthropathy, along with muscle bleeding. Prophylactic factor medication administered intravenously several times per week decreases but does not eliminate bleeding. Most efforts to eliminate breakthrough bleeding on prophylaxis alter medication regimens to increase factor levels; however, this is often not successful and comes with increased financial burden and/or more frequent injections. The effort to eliminate breakthrough bleeding is limited by an incomplete understanding of bleeding biomechanics. This knowledge gap also constrains choices for safe and effective physical activity, which is important in persons with hemophilia (PwH) to prevent obesity, improve social functioning, and decrease mental health concerns. This study develops methods to objectively measure forces related to lower extremity joint and muscle bleeding in PwH, in order to fulfill the long-term goal of decreasing bleeding risk. This long-term goal will be accomplished in a future study that will collect data to build a time-dependent statistical model of bleeding risk that includes hemostatic, joint fragility, and biomechanical bleeding risk components. The objectives of the current study are to determine how past joint bleeding influences asymmetry in lower extremity joint loading, measured in a Motion Lab using motion capture and force plate technology (aim 1); to determine the influence of motion lab asymmetry on future lower extremity joint and muscle bleeding (aim 2); and to develop tools to collect motion data outside the Motion Lab using inertial measurement units (IMUs) (aim 3). The immediate goals of the candidate for this K23 award, Dr. Beth Warren, are to add new skills to her bioengineering and hematology background. These include motion measurement techniques inside and outside the Motion Lab, including signal processing techniques; hemophilia joint outcome measurement and meaning; and statistical model planning for future studies. Achieving these goals will support her long-term career goal to become a leading expert in hemophilia joint outcomes and activity-associated bleeding risk. Dr. Warren will accomplish her research and training aims with the support of her mentors, Dr. Marilyn Manco-Johnson (hemophilia clinical research) and Dr. James Carollo (biomechanics, movement analysis). The University of Colorado Hemophilia and Thrombosis Center (UC-HTC) will provide world-class infrastructure to support Dr. Warren’s career development and research objectives, including facilities and research staff with extensive experience and expertise in hemophilia clinical research. The University of Colorado provides junior faculty members with numerous opportunities to facilitate the transition to research career independence. By completing her research and training aims, Dr. Warren will advance the science of objective measurement of bleeding biomechanics, while also obtaining experience and training necessary to begin her career as an independent investigator.

项目摘要/摘要 血友病是闭合因子VIII或IX的遗传缺陷，导致关节出血和残废 关节病，以及肌肉出血。预防性因子药物静脉注射几个 每周的时间减少，但不会消除出血。消除突破性出血的最多努力 预防改变药物方案以提高因子水平；但是，这通常不成功，并且来了 随着财务燃烧和/或更频繁的注射。消除突破出血的努力 受到出血生物力学的不完全理解的限制。这个知识差距也限制了 选择安全有效的体育锻炼，这在血友病（PWH）的人中很重要，以防止 肥胖，改善社会功能并减少心理健康问题。这项研究开发了方法 与下肢关节和PWH中的肌肉出血有关的客观测量的力量，以实现 降低出血风险的长期目标。这个长期目标将在以后的研究中实现 将收集数据以建立一个时间依赖性的出血风险统计模型，其中包括止血，关节脆弱性， 和生物力学出血风险成分。当前研究的对象是确定过去 关节出血影响下肢关节载荷中的不对称性，在运动实验室中使用运动测量 捕获和强制板技术（AIM 1）；确定运动实验室不对称对未来下部的影响 肢体和肌肉出血（AIM 2）；并开发工具以在运动实验室之外收集运动数据 使用惯性测量单元（IMU）（AIM 3）。 该K23奖候选人的直接目标贝丝·沃伦（Beth Warren）博士是为她增添新技能 生物工程和血液学背景。这些包括运动测量技术内部和外部 运动实验室，包括信号处理技术；血友病联合结局测量和意义； 以及未来研究的统计模型计划。实现这些目标将支持她长期职业目标 成为血友病联合结局和活动相关的出血风险的领先专家。 沃伦博士将在导师玛丽莲博士的支持下完成她的研究和培训目标 Manco-Johnson（血友病临床研究）和James Carollo博士（生物力学，运动分析）。这 科罗拉多大学血友病与血栓形成中心（UC-HTC）将为世界一流的基础设施提供 支持沃伦博士的职业发展和研究目标，包括设施和研究人员 血友病临床研究的丰富经验和专业知识。科罗拉多大学提供初中 有很多机会促进过渡到研究职业独立性的教职员工。经过 完成她的研究和培训目标，沃伦博士将进步 流血生物力学，同时还获得了必要的经验和培训，以开始她的职业生涯 独立研究者。