Biological Markers of System Burden in Symptomatic Knee OA: A Prospective Study

有症状的膝关节 OA 系统负担的生物标志物：一项前瞻性研究

• 批准号: 8510154
• 负责人: Kimberly Theresa Sibille
• 金额: $ 11.89万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8510154
• 关键词: Acute Pain; Address; Adult; Affect; African American; American; Area; Arthritis; Biological; Biological Factors; Biological Markers; Biological Process; Cardiovascular system; Cell Aging; Chromosomes; Chronic; Chronic stress; Clinical; Clinical Sciences; Communities; Complex; DNA; Degenerative polyarthritis; Dentistry; Development; Discrimination; Disease; Disease Progression; Doctor of Medicine; Doctor of Philosophy; Education; Elderly; Environment; Equilibrium; Ethnic group; Florida; Funding; Genetic; Goals; Grant; Hyperalgesia; Immune; Immunology; Individual; Individual Differences; Inflammation; Institutes; Interest Group; Intervention; Investigation; Journals; Knee; Knee Osteoarthritis; Laboratories; Length; Leukocytes; Literature; Manuscripts; Measures; Medical; Medical Research; Mentored Patient-Oriented Research Career Development Award; Mentors; Metabolic; Metabolism; Modeling; Musculoskeletal Diseases; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Neurosecretory Systems; Not Hispanic or Latino; Pain; Pain Measurement; Pain Research; Patient Self-Report; Persistent pain; Physiological; Prevention; Prospective Studies; Proxy; Psychosocial Factor; Psychosocial Stress; Quality of life; Reporting; Research; Research Personnel; Research Support; Research Training; Resources; Role; Scholarship; Severities; Severity of illness; Stress; Symptoms; System; Telomere Shortening; Time; Training; Translational Research; United States; Universities; Work; allostatic load; behavioral/social science; biological systems; biopsychosocial; career; career development; chronic pain; clinical efficacy; college; coping; cytokine; design; disability; ethnic difference; experience; field study; follow-up; functional decline; health application; improved; indexing; interest; knowledge base; meetings; multidisciplinary; novel; optimism; pain inhibition; patient oriented research; programs; public health relevance; research and development; research study; resilience; skills; skin disorder; statistics; stressor; symposium; telomere; treatment response

DESCRIPTION (provided by applicant): Osteoarthritis (OA) is a leading cause of pain and functional limitation in the United States. There are significant individual and ethnic group differences in the experience of OA. An improved understanding of factors contributing to the disparities and a biomarker reflecting the variability is needed. The research goals and career development training objectives identified in this K23 Mentored Patient-Oriented Research Career Development Award application have been developed to obtain the training and experience to pursue investigations of the biological interface of chronic pain and psychosocial stress in knee OA. Entitled Biological Markers of System Burden in Symptomatic Knee OA: A Prospective Study, the proposed study expands on current research supported in part through the Basic Behavioral and Social Science Opportunity Network (OppNet) specific to Dr. Sibille's research interests and career ambitions. Additionally, the proposed research aligns with the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Long Range Plan for Fiscal Years 2010-2014 and the 2010 NIAMS Roundtable Summary. My career goals are to: 1) excel in an academic medical setting as a clinical/translational pain investigator with expertise in osteoarthritis involved in patient-oriented research and 2) contribute to the research and medical community through scholarship and education with an overall goal of improving the management, functioning, and quality of life for individuals with osteoarthritis and other pain-related conditions. My career development training objectives incorporate activities and experiences pertinent to my research goals and necessary to obtain R01 funding by 2016. Objective 1: Develop a comprehensive knowledge-base in osteoarthritis Objective 2: Broaden skills in multi-modal assessment of pain and functional limitations Objective 3: Increase understanding of genetics and stress-related biological systems Objective 4: Enhance management skills necessary to function as an independent researcher Objective 5: Strengthen skills in clinical/translational research, statistics, and scholarship My career development research and training efforts will be guided by an exceptional mentoring team, Roger Fillingim, Ph.D., Primary Mentor, will provide guidance and oversight in the multi-modal assessment of pain and functional limitations; the integration of biological and psychosocial factors; and my overall career development. Roland Staud, M.D., will oversee the development of a comprehensive knowledge-base in osteoarthritis. Christiaan Leeuwenburgh, Ph.D., Co-Mentor, will provide direction in areas related to metabolic processes, evaluating biological markers, and developing the skills necessary for translational investigation. Taimour Langaee, Ph.D., Co-Mentor, will assist with training and development in the areas of immunology, genetics, and telomere measures. Bruce McEwen, Ph.D., Consultant/Co-Mentor, will direct my training specific to neuroendocrine functioning, the effects of stress on health, and the application of the allostatic load model in the study of knee osteoarthritis. My transition to research independence will also be benefited by relationships developed in the OA Network, an advisory and collaborative group of clinician/researchers. A comprehensive training plan has been developed that includes didactic coursework, clinical and laboratory experience, directed study; individual and group mentoring meetings; involvement in lab meetings, research interest groups, journal clubs; attendance and presentations at professional conferences; manuscript and grant development; research responsibilities; and academic/department contributions. Completion of the proposed training plan will include obtaining a Certificate of Clinical Translational Research by 2014 through the University of Florida Clinical and Translational Science Institute (CTSI). The training environment at the University of Florida is outstanding. In addition to the educational programs and resources available through the CTSI, I have the opportunity to train and work with accomplished basic and clinical researchers through the Comprehensive Center for Pain Research, the College of Dentistry, the Pain Research and Intervention Center of Excellence, and the Claude D. Pepper Older Americans Independence Center. The proposed research study is novel, multidisciplinary, and translational. The objectives of the study are to prospectively evaluate associations of pain and functional limitations with a developing measure of system burden in ethnically diverse older adults with and without knee OA and explore the role of various biopsychosocial factors that may be protective or increase vulnerability for pain and functional decline. There are numerous opportunities with significant clinical implications to extend the translational research efforts proposed. Long-term goals are to elucidate biological markers of system burden in knee OA, delineate resilience and vulnerability factors for prevention and treatment, and establish a composite of biomarkers for evaluating the efficacy of clinical interventions. Importantly, the information generated by this research will make a significant scientific contribution as this represents the first study to prospectively examine biological markers of system burden, knee OA status, pain severity, and functional limitations among ethnically diverse older adults with and without knee OA.

描述（由申请人提供）：骨关节炎（OA）是美国疼痛和功能受限的主要原因。OA的经历存在显著的个体和种族差异。需要更好地理解导致差异的因素和反映变异性的生物标志物。在K23指导的以患者为导向的研究职业发展奖申请中确定的研究目标和职业发展培训目标已经开发，以获得培训和经验，以研究膝关节OA中慢性疼痛和心理社会压力的生物学界面。该研究名为《膝关节OA系统负担的生物学标志物：一项前瞻性研究》，该研究扩展了目前的研究，部分研究是通过基本行为和社会科学机会网络（OppNet）支持的，具体针对Sibille博士的研究兴趣和职业抱负。此外，拟议的研究符合国家关节炎和肌肉骨骼和皮肤疾病研究所（NIAMS）2010-2014财年长期计划和2010年NIAMS圆桌会议摘要。 我的职业目标是：1）在学术医疗环境中表现出色，是一名临床/翻译疼痛研究者，具有参与以患者为导向的研究的骨关节炎方面的专业知识，2）为研究做出贡献 通过奖学金和教育与医学界的总体目标是改善管理，功能和生活质量的个人与骨关节炎和其他疼痛相关的条件。我的职业发展培训目标包括与我的研究目标相关的活动和经验，以及到2016年获得R 01资助所必需的活动和经验。 目标一：发展全面的骨关节炎知识库目标2：疼痛和功能限制多模式评估的Brochure技能目标3：增加对遗传学和压力相关生物系统的理解目标4：提高作为独立研究者所需的管理技能目标5：加强临床/转化研究，统计学和奖学金的技能我的职业发展研究和培训工作将由一个特殊的指导团队，罗杰Fillingim，博士，主要导师，将在疼痛和功能限制的多模式评估中提供指导和监督;生物和心理社会因素的整合;以及我的整体职业发展。医学博士罗兰·斯托德将监督骨关节炎综合知识库的发展。Christiaan Leeuwenburgh博士，共同导师，将提供方向，在相关领域的代谢过程，评估生物标志物，并发展必要的翻译研究的技能。Taimour Langaee博士，共同导师，将协助在免疫学，遗传学和端粒措施领域的培训和发展。布鲁斯·麦克尤恩博士，顾问/共同导师，将指导我的培训，特别是神经内分泌功能，压力对健康的影响，以及非稳态负荷模型在膝关节骨关节炎研究中的应用。我向研究独立性的转变也将受益于OA网络中发展的关系，OA网络是一个由临床医生/研究人员组成的咨询和协作小组。 已经制定了一个全面的培训计划，包括教学课程，临床和实验室经验，指导研究;个人和小组辅导会议;参与实验室会议，研究兴趣小组，期刊俱乐部;出席和专业会议的演讲;手稿和赠款开发;研究责任;和学术/部门的贡献。完成拟议的培训计划将包括通过佛罗里达大学临床和转化科学研究所（CTSI）在2014年获得临床转化研究证书。佛罗里达大学的培训环境非常出色。除了通过CTSI提供的教育计划和资源外，我还有机会通过疼痛研究综合中心，牙科学院，疼痛研究和干预卓越中心以及Claude D.佩珀老年美国人独立中心。 拟议的研究是新颖的，多学科的，和翻译。本研究的目的是前瞻性地评估疼痛和功能限制与发展中的系统负担的措施在不同种族的老年人与膝关节骨性关节炎和探讨各种生物心理社会因素的作用，可能是保护或增加脆弱性的疼痛和功能下降。 有许多具有重大临床意义的机会来扩展所提出的转化研究工作。长期目标是阐明膝关节OA系统负荷的生物学标志物，描述预防和治疗的弹性和脆弱性因素，并建立一个生物标志物的复合物，用于评估临床干预措施的有效性。重要的是，本研究产生的信息将做出重大的科学贡献，因为这是第一项前瞻性研究，在患有和不患有膝关节OA的不同种族老年人中检查系统负荷、膝关节OA状态、疼痛严重程度和功能限制的生物标志物。