A Stress and Pain Self-management m-Health App for Adult Outpatients with Sickle Cell Disease

适用于镰状细胞病成人门诊患者的压力和疼痛自我管理移动健康应用程序

• 批准号: 10286055
• 负责人: Miriam Omelebele Ezenwa
• 金额: $ 38.13万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-07 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10286055
• 关键词: Administrative Supplement; Adult; Affect; Affinity; Age; Age-Years; Alzheimer' s Disease; Alzheimer' s disease related dementia; Automobile Driving; Binding; Biological Markers; Blood; Blood Vessels; Brain; Brain hemorrhage; Cerebral Infarction; Child; Childhood stroke; Cognitive; Cognitive deficits; Complex; Data; Dementia; Diagnosis; Emotional; Employment Status; Endothelium; Future; Genetic; Genotype; Goals; Haptoglobins; Heme; Hemoglobin; Human; Incidence; Individual; Inflammatory; Intervention Studies; Mediating; Mobile Health Application; Nervous System Trauma; Neurocognitive; Neuropsychological Tests; Nociception; Outcome; Outpatients; Oxidation-Reduction; Pain; Pathway interactions; Patients; Prevention trial; Property; Protein Isoforms; Proteins; Quality of life; Recording of previous events; Regulation; Reporting; Research; Risk; Risk Assessment; Risk Factors; Role; Sampling; Sensory; Severities; Sickle Cell; Sickle Cell Anemia; Stress; Stroke; Stroke prevention; Structure; TLR2 gene; TLR4 gene; Testing; Time; Toll-like receptors; Toxic effect; United States National Institutes of Health; Vascular Cognitive Impairment; dementia risk; design; executive function; extracellular; functional outcomes; insight; mHealth; mortality; mutant; neurocognitive test; novel; pain perception; pain processing; pain self-management; painful neuropathy; personalized medicine; potential biomarker; prevent; protein aggregation; receptor; response; scavenger receptor; vascular contributions; vascular injury; virtual

Project Summary/Abstract In response to PA-18-591-NOT-AG-20-034, our long-term goal is to understand the potential influence of unrecognized vascular cognitive impairment (VCI)/dementia on pain perception among adults with sickle cell disease (SCD) who are referred to a mHealth pain intervention study (1R01NR018848-01A1). The most typical reason for permanent neurological damage in patients with SCD is silent cerebral infarct, which occurs in approximately 39% of children by 18 years1 of age and over 50% of adults by 30 years of age.1 Vascular injury to the brain can directly modify pain processing by affecting ascending and descending nociceptive pathways2 and indirectly modify pain processing by affecting cognitive and emotional pathways.2 However, in patients with SCD, the effect of VCI/dementia on pain reports are virtually unknown because studies rarely include comprehensive neurocognitive testing or assessment of biomarker indicators of risk for dementia from vaso- occlusion-related silent cerebral infarcts and stroke, such as haptoglobin. The haptoglobin genotype (Hp1-1, Hp2-1, or Hp2-2) results in proteins with different structures, resulting in a differential ability to protect against and clear extracellular toxic hemoglobin (Hb). Understanding the biomarker indicators/genetic basis for VCI/dementia that may alter pain perceptions is pertinent for driving personalized therapies for patients, including those with SCD, Alzheimer's disease, or Alzheimer's disease-related dementia (AD/ADRD). In 90 adults with SCD who are referred to the m-Health study, the specific aims of this administrative supplement are to: Aim 1: Compare the proportion with VCI/dementia (neurocognitive status) among patients with Hp2-2 and patients with HP2-1 or Hp1-1. Aim 2: Compare (a) sensory pain perception (intensity, quality, neuropathic pain) and (b) concentrations of proinflammatory molecules among Hp2-2 genotype and Hp2-1 or Hp1-1 genotypes. We expect that more than half of the sample will have previously undetected VCI/dementia and that a larger proportion of patients with the Hp2-2 genotype will have VCI/dementia than those with the HP2-1 or Hp1-1 genotype. We also expect that the patients with HP2-2 will have worse pain and more pro- inflammatory molecules as compared to patients with HP2-1 or Hp1-1. These preliminary data will lead to an NIH-R01 focused on testing the hypothesis that Hp2-2 patients with SCD who have VCI/dementia will have worse pain and more pro-inflammatory molecules as compared to HP2-1 or Hp1-1 patients. Future studies will be designed to tease out the contributions of haptoglobin genotype and its regulation of pro-oxidative and pro- inflammatory properties of free hemoglobin to VIC/dementia in adult outpatients with SCD and pain. Other studies will be designed to test effects of transfusing the right Hp-typed blood (or isoform) on mitigation of many, if not all, the toxicity mediated by free hemoglobin and sickled cells. The impact of our findings would be enormous because they could be extrapolated to patients with AD/ADRD that currently affects 50 million individuals worldwide, with 10 million new cases diagnosed annually.3

项目摘要/摘要 为了回应PA-18-591-NOT-AG-20-034，我们的长期目标是了解 未识别的血管认知障碍（VCI）/痴呆症对镰状细胞的疼痛感知 疾病（SCD）被称为MHealth疼痛干预研究（1R01NR01NR018848-01A1）。最典型的 SCD患者的永久神经系统损害的原因是无声的脑梗塞，发生在 大约39％的儿童到18岁，到30岁的成年人中的50％以上。1血管损伤 大脑可以通过影响上升和下降伤害感途径直接改变疼痛处理2 并通过影响认知和情感途径间接修改疼痛处理。2然而，患者 使用SCD，VCI/痴呆症对疼痛报告的影响几乎是未知的，因为研究很少包括 全面的神经认知测试或评估生物标志物的痴呆风险指标 与闭塞有关的无声脑梗塞和中风，例如触觉。 Haptoglobin基因型（HP1-1， HP2-1或HP2-2）导致具有不同结构的蛋白质，从而具有差异的能力来防止 并清除细胞外有毒血红蛋白（HB）。了解生物标志物指标/遗传基础 可能会改变疼痛感知的VCI/痴呆症与为患者驾驶个性化疗法有关， 包括患有SCD，阿尔茨海默氏病或​​阿尔茨海默氏病有关的患者（AD/ADRD）。在90中 具有SCD的成年人被转诊为M-Health研究，此行政补充的具体目的是 到：AIM 1：将HP2-2患者和VCI/痴呆症（神经认知状况）进行比较 患有HP2-1或HP1-1的患者。目标2：比较（a）感觉疼痛感知（强度，质量，神经性疗法 疼痛）和（b）HP2-2基因型和HP2-1或HP1-1之间促炎分子的浓度 基因型。我们预计，以前有一半以上的样本将没有发现的VCI/痴呆症和 HP2-2基因型的患者比例更大，比患有HP2-1的患者将具有VCI/痴呆症 或HP1-1基因型。我们还期望HP2-2患者的疼痛更严重，并且会更加亲切 与HP2-1或HP1-1患者相比，炎症分子。这些初步数据将导致 NIH-R01的重点是检验以下假设：患有VCI/痴呆的SCD患者将具有 与HP2-1或HP1-1患者相比，疼痛和更多促炎分子。未来的研究将 设计旨在取消触觉蛋白基因型的贡献及其对促氧化和促氧化的调节 SCD和疼痛的成年门诊患者中游离血红蛋白与VIC/痴呆症的炎症特性。其他 研究将旨在测试右HP型血液（或同工型）对缓解的影响的影响 许多（如果不是全部）毒性是由游离血红蛋白和镰状细胞介导的。我们发现的影响将是 巨型 全球个人，每年诊断出1000万例新病例。3