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

项目概要/摘要 作为对PA-18-591-NOT-AG-20-034的回应，我们的长期目标是了解 未被识别的血管性认知障碍（VCI）/痴呆对镰状细胞病成人疼痛感知的影响 参与mHealth疼痛干预研究（1 R 01 NR 018848 - 01 A1）的SCD患者。最典型的 SCD患者永久性神经损伤的原因是无症状性脑梗死， 约39%的18岁儿童1和超过50%的30岁成人1血管损伤 可以通过影响上行和下行伤害性通路直接改变疼痛处理2 并通过影响认知和情感途径间接改变疼痛处理。2然而，在患者中， 对于SCD，VCI/痴呆对疼痛报告的影响实际上是未知的，因为研究很少包括 全面的神经认知测试或评估血管性痴呆风险的生物标志物指标， 闭塞相关的无症状脑梗死和中风，如触珠蛋白。结合珠蛋白基因型（Hp 1 -1， Hp 2 -1或Hp 2 -2）导致蛋白质具有不同的结构，从而导致不同的保护能力， 并清除细胞外毒性血红蛋白（Hb）。了解生物标志物指标/遗传基础 可能改变疼痛感知的VCI/痴呆症与推动患者个性化治疗有关， 包括患有SCD、阿尔茨海默病或阿尔茨海默病相关痴呆（AD/ADRD）的那些。在90 成人SCD谁是转介到移动健康研究，这一行政补充的具体目标是 目的：目的1：比较Hp 2 -2和Hp 2 - 3患者中VCI/痴呆（神经认知状态）的比例， HP 2 -1或HP 1 -1患者。目的2：比较（a）感觉疼痛感知（强度、质量、神经性疼痛） 疼痛）和（B）Hp 2 -2基因型和Hp 2 -1或Hp 1 -1之间的促炎分子浓度 基因型我们预计，超过一半的样本将有以前未检测到的VCI/痴呆， 具有Hp 2 -2基因型的患者比具有HP 2 -1基因型的患者更大比例患有VCI/痴呆。 或Hp 1 -1基因型。我们还预计HP 2 -2患者的疼痛更严重， 与HP 2 -1或Hp 1 -1患者相比，这些初步数据将导致 NIH-R 01集中于检验假设，即患有VCI/痴呆的Hp 2 -2 SCD患者将有 与HP 2 -1或Hp 1 -1患者相比，更严重的疼痛和更多的促炎分子。未来的研究将 旨在梳理出结合珠蛋白基因型及其对促氧化和促- 在患有SCD和疼痛的成人门诊患者中游离血红蛋白对维克/痴呆的炎症特性其他 研究将被设计为测试使用正确的Hp型血（或同种型）对缓解 许多（如果不是全部）毒性由游离血红蛋白和镰状细胞介导。我们的发现的影响将是 因为它们可以外推到目前影响5000万的AD/ADRD患者 全世界有1000万人，每年有1 000万新病例被诊断出来。

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