Biobehavioral mechanisms underlying symptoms and healing outcomes in older individuals with CVLU

老年 CVLU 患者症状和治愈结果的生物行为机制

• 批准号: 10092225
• 负责人: DEBRA E LYON
• 金额: $ 58.59万
• 依托单位: UNIVERSITY OF FLORIDA
• 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 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10092225
• 关键词: Address; Adherence; Affect; Age; Age-Years; Aging; Amputation; Antibiotics; Anxiety; Area; Bayesian Modeling; Biological; Biology; Biometry; Body mass index; C-reactive protein; Characteristics; Chronic; Chronic Disease; Complex; Debridement; Detection; Development; Disease; Distress; Elderly; Enzymes; Epigenetic Process; Ethnic Origin; Fatigue; Foundations; Goals; Habits; Health; Health Expenditures; Immune; Impaired cognition; Impaired healing; Incidence; Individual; Infection; Inflammation; Inflammatory; Integration Host Factors; Intervention; Knowledge; Label; Leg; Leg Ulcer; Life Style; Longitudinal Studies; Matrix Metalloproteinases; Mental Depression; MicroRNAs; Microbe; Microbial Biofilms; Minority; Modeling; Molecular; Molecular Biology; Morbidity - disease rate; Nutritional status; Odors; Outcome; Pain; Pathogenicity; Patients; Persons; Population; Prevalence; Pruritus; Public Health; Quality of life; Race; Research; Science; Self Management; Severities; Standardization; Sterile coverings; Symptoms; Technology; Testing; Time; Translational Research; Ulcer; United States; United States National Institutes of Health; Venous; Vulnerable Populations; aging population; anxiety symptoms; biobehavior; comorbidity; cytokine; depressive symptoms; disability; functional status; healing; human old age (65+); immune activation; innovation; microbial; multidisciplinary; non-healing wounds; pain symptom; patient oriented; pressure; prevent; programs; public health relevance; sex; symptom cluster; symptom science; systemic inflammatory response; targeted treatment; wound; wound bed; wound healing; wound treatment

ABSTRACT Our long-term goal is to elucidate the complex biobehavioral mechanisms responsible for symptoms and healing outcomes for older adults’ with venous leg ulcers (VLUs) for the development of targeted therapies that address both the patient-oriented outcomes and healing outcomes in this growing group of affected individuals. VLUs, which account for 70–90% of ulcers found in the lower leg, affect 2 million persons annually, including nearly 4% of people over age 65 years. To date, the basic biology underlying the development and persistence of VLUs and the influence of aging and multiple disease conditions on wound healing are generally not well understood. Individuals living with chronic VLU (CVLU) have a high symptom burden of both wound-related symptoms and symptoms of pain, depression, anxiety, fatigue and cognitive dysfunction, collectively labeled as “psychoneurologic symptoms (PNS).” Guided by the National Institutes of Health Symptom Science Model (NIH-SSM) framework, the central hypothesis of this application is that there are interrelated molecular mechanisms by which the immune activation that contributes to the development and persistence of CVLU also leads to the development, persistence and severity of PNS. The specific aims of the proposed study are to: (1) Characterize the strength of the associations at baseline among patient-host factors, systemic inflammation, and wound microenvironment with wound area and symptoms (PNS and wound-related); and, (2) Test associations and models over time for: (a) Patient-host factors and systemic inflammation with wound microenvironment; (b) Patient-host factors and wound microenvironment with systemic inflammation; (c) Patient-host factors, systemic inflammation, and wound microenvironment with wound healing; (d) Patient-host factors, systemic inflammation, and wound microenvironment with symptoms (PNS and wound-related) and (e) Patient-host factors, systemic inflammation, wound microenvironment and wound healing with symptoms (PNS and wound-related). To achieve the specific aims, we will longitudinally examine 200 older adults (age >60) who are receiving state of the art, standardized wound treatment biweekly across eight weeks time. We will fully characterize patient-host characteristics (age, comorbidities, sex, race/ethnicity, BMI, nutritional status, lifestyle habits, and wound treatment [pressure therapy, debridement, antibiotics]); systemic inflammatory activation (C-reactive protein and cytokines); wound microenvironment factors (local inflammation [Matrix metalloproteinase (MMP) enzymes C-reactive protein, cytokines], biofilm, and micro RNAs); symptoms (PNS [cognitive dysfunction, pain, fatigue, and depressive/anxiety symptoms] and wound-related); and wound characteristics and healing trajectory at the five timepoints. This knowledge is critical to provide a foundation for developing targeted interventions to address this critical health problem from a holistic perspective and to provide a basis for preventing or reversing the adverse health outcomes of CVLUs, a condition that differentially affects older and minority individuals.

摘要 我们的长期目标是阐明导致症状的复杂生物行为机制， 老年下肢静脉溃疡（VLU）患者的愈合结果，以开发靶向治疗， 解决这一日益增长的受影响个体群体中以患者为导向的结果和愈合结果。 VLU占小腿溃疡的70-90%，每年影响200万人，包括 近4%的人超过65岁。到目前为止，发展和持续的基础生物学 以及年龄和多种疾病条件对伤口愈合的影响通常不好 明白患有慢性VLU（CVLU）的个体具有高的创伤相关症状负担， 疼痛、抑郁、焦虑、疲劳和认知功能障碍的症状和症状，统称为 精神神经症状（PNS）由美国国立卫生研究院症状科学模型指导 （NIH-SSM）框架，该应用的中心假设是存在相互关联的分子 免疫激活有助于CVLU的发展和持续的机制 也导致PNS的发展、持续和严重性。拟议研究的具体目标是 目的：（1）描述基线时患者-宿主因素、系统性 炎症和伤口微环境与伤口面积和症状（PNS和伤口相关）;以及， (2)测试随时间推移的相关性和模型：（a）患者-宿主因素和全身炎症与伤口 （B）患者-宿主因素和具有全身性炎症的伤口微环境;（c） 患者-宿主因素、全身性炎症和伤口愈合的伤口微环境;（d）患者-宿主因素 因素、全身性炎症和伤口微环境与症状（PNS和伤口相关）和（e） 患者-宿主因素、全身炎症、伤口微环境和伤口愈合伴症状（PNS 与伤口有关）。为了实现特定的目标，我们将纵向研究200名老年人（年龄>60岁） 他们正在接受最先进的标准化伤口治疗，每两周一次，为期八周。我们将 充分表征患者-宿主特征（年龄、合并症、性别、人种/种族、BMI、营养状况， 生活习惯和伤口治疗[压力疗法、清创术、抗生素]）;全身炎症 活化（C-反应蛋白和细胞因子）;伤口微环境因子（局部炎症[基质 金属蛋白酶（MMP）酶C反应蛋白、细胞因子]、生物膜和微RNA）;症状（PNS [认知功能障碍、疼痛、疲劳和抑郁/焦虑症状]和伤口相关）;和伤口 在五个时间点的特征和愈合轨迹。这些知识对于提供基础至关重要 制定有针对性的干预措施，从整体角度解决这一关键的健康问题， 为预防或逆转CVLU的不良健康结果提供基础，CVLU是一种 对老年人和少数民族的影响不同。