Insights into Sickle Cell Trait and Sickle Cell Disease

镰状细胞性状和镰状细胞病的见解

• 批准号: 10267118
• 负责人: Vence L Bonham
• 金额: $ 28.45万
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10267118
• 关键词: Accounting; Address; Affect; African; African American; American; Anemia; Animals; Arabs; Behavior Therapy; Bibliography; COVID-19 pandemic; Cardiomyopathies; Case Series; Case Study; Cells; Cessation of life; Childhood; Chronic Kidney Failure; Clinical; Codon Nucleotides; Complication; Cross-Sectional Studies; Data; Data Set; Deep Vein Thrombosis; Diabetic Foot Ulcer; Disease; Erythrocyte Membrane; Ethnography; Etiology; Exertion; Frequencies; Genes; Genetic; Genetic study; Genomic approach; Genomics; Goals; Guidelines; Health; Health behavior; Heart failure; Height; Hemolysis; Hemolytic Anemia; Hispanics; Hospitalization; Impairment; In Vitro; Incidence; Individual; Internal Medicine; Interview; Laboratories; Leg; Leg Ulcer; Low income; Mutation; Nature; Organ; Outcome; Pain; Participant; Patients; Personal Satisfaction; Physical environment; Physiological; Point Mutation; Population; Predisposition; Prevalence Study; Procedures; Process; Proteinuria; Psychosocial Factor; Public Policy; Published Comment; Publishing; Pulmonary Embolism; Quality of life; Recording of previous events; Recurrence; Reporting; Research; Resistance; Resources; Rhabdomyolysis; Risk; Role; Sampling; Severities; Severity of illness; Sickle Cell; Sickle Cell Anemia; Sickle Cell Trait; Sleep disturbances; Social Environment; Social Functioning; Social Sciences; Stress; Stroke; Surveys; Symptoms; Thromboembolism; Time; Ulcer; Underinsured; United States; Variant; Weight; Well in self; behavioral health; beta Globin; carrier testing; clinical care; comorbidity; design; editorial; emotional distress; genome sequencing; healing; health care quality; health care service; health care service utilization; improved; inclusion criteria; insight; interest; meeting abstracts; microbial; microbial community; microbiome; microbiome research; nonEnglish language; offspring; pandemic disease; patient population; perceived stress; premature; programs; psychosocial; recruit; research study; resilience; screening program; skin microbiome; social; southeast Asian; stress resilience; systematic review; whole genome; working group

GOAL: SYSTEMATIC REVIEW OF CLINICAL COMPLICATIONS OF SICKLE CELL TRAIT (SCT) For Aim 1: A systematic review of published original research articles between January 1970 and June 30, 2018 that reported an association between SCT and clinical outcomes of interest were reviewed by an expert working group. We followed standard procedures for systematic reviews and reported results according to Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines. The study excluded: 1) non-English language research articles; 2) research articles that reported exclusively on patients with sickle cell disease, in vitro cells, or nonhuman animals; 3) research articles that solely examined physiological mechanisms, laboratory parameters, or had no information on clinical outcomes; 4) prevalence studies, case reports, case series, meeting abstracts, editorials and commentaries; and 5) systematic reviews and review articles after their bibliographies had been reviewed for previously unidentified articles.) Of 7,083 screened studies, 41 met inclusion criteria. There was strong evidence for a positive association between SCT and risk for pulmonary embolism, proteinuria, and chronic kidney disease. There was moderately strong evidence for a positive association between SCT and exertional rhabdomyolysis and for a null association between SCT and deep venous thrombosis, heart failure/cardiomyopathy, stroke, and pediatric height/weight. Absolute risks for the thromboembolism and rhabdomyolysis complications were small. There were either insufficient data or low strength of evidence regarding associations for the remaining 15 clinical outcomes reported in these studies. See Naik RP. et al., Clinical Outcomes Associated With Sickle Cell Trait, Annals of Internal Medicine. 169, 619 (2018). GOAL: EXPLORING THE GENOMIC AND ENVIRONMENTAL CONTRIBUTIONS TO SICKLE CELL DISEASE AND LEG ULCERS Aim 2: The study of leg ulcers in sickle cell disease is ongoing. As of September 1, 2019, we have recruited 235 participants. We have increased our accrual goal for the skin microbiome study up to 250 participants. We will recruit and sample participants with active ulcers, currently with a healed leg ulcer, and those with no previous history of leg ulcers. Additionally, we will compare a previously published microbiome dataset from diabetic foot ulcers to SCD leg ulcers to identify microbial signatures (similarities or differences) that exist in the microbial communities present in the different ulcers, which may be important in the healing process. Aim 3: We will conduct a cross-sectional study to investigate, resilience, stress, social function, health behaviors, and quality of life indicators for each participant with the goal of identifying environmental (i.e. social, physical, and psychosocial) factors that may impact sickle cell disease and the formation and healing of leg ulcers. Aim 4: We will conduct genomic sequencing to seek to identify the role of genetic modifiers in patients with and without leg ulcers. Specifically, we will conduct whole genome sequencing in the participants to study the genetic factors responsible for variation in leg ulceration in our patient population. Aim 5: We will develop and evaluate a return of genomic results program for INSIGHTS study participants. We will conduct an ethnographic study to collect longitudinal data to examine study participants that receive genomics results and assess health behaviors and treatment decisions over time. We predict that the population of study participants that are most in need of support in addressing unexpected genomic results will be low-income and under-insured individuals. GOAL: EXAMINE COVID-19 PANDEMIC IMPACTS INDIVIDUALS LIVING with SICKLE CELL DISEASE Aim 6 and 7: We will survey and conduct interviews to understand how the COVID-19 pandemic impacts individuals living with SCD, with a focus on the major physical and psychosocial facets of their disease referenced above including the presentation of pain, health care utilization, and social and behavioral health. We are particularly interested in how disease severity, pain frequency and severity, frequency and quality of healthcare services, emotional distress, sleep disturbance, perceived stress, and resilience affect the overall psychosocial well-being of individuals living with SCD during this current pandemic.

目标：系统评价镰状细胞性状 (SCT) 的临床并发症 目标 1：对 1970 年 1 月至 2018 年 6 月 30 日期间发表的原始研究文章进行系统回顾，这些文章报告了 SCT 与感兴趣的临床结果之间的关联，并由专家工作组进行了审查。我们遵循系统评价的标准程序，并根据系统评价的首选报告项目 (PRISMA) 指南报告结果。 该研究排除：1）非英语研究文章； 2) 专门报道镰状细胞病患者、体外细胞或非人类动物的研究文章； 3）仅考察生理机制、实验室参数或没有临床结果信息的研究文章； 4) 患病率研究、病例报告、病例系列、会议摘要、社论和评论； 5) 系统综述和在对之前未确定的文章进行审查后对参考书目进行综述。）在 7,083 项筛选研究中，有 41 项符合纳入标准。 有强有力的证据表明 SCT 与肺栓塞、蛋白尿和慢性肾脏病的风险呈正相关。 有中等强度的证据表明，SCT 与劳力性横纹肌溶解症之间存在正相关，而 SCT 与深静脉血栓形成、心力衰竭/心肌病、中风和儿童身高/体重之间则无相关性。血栓栓塞和横纹肌溶解并发症的绝对风险很小。这些研究中报告的其余 15 项临床结果的相关性要么数据不足，要么证据强度低。 参见奈克·RP。等人，与镰状细胞性状相关的临床结果，内科医学年鉴。 169、619（2018）。 目标：探索基因组和环境对镰状细胞病和腿部溃疡的影响 目标 2：镰状细胞病引起的腿部溃疡的研究正在进行中。截至2019年9月1日，我们已招募了235名参与者。我们已将皮肤微生物组研究的招募目标增加至 250 名参与者。我们将招募患有活动性溃疡、目前已治愈腿部溃疡以及以前没有腿部溃疡病史的参与者并进行抽样。此外，我们将比较之前发布的糖尿病足溃疡和 SCD 腿部溃疡的微生物组数据集，以确定不同溃疡中存在的微生物群落中存在的微生物特征（相似性或差异），这在愈合过程中可能很重要。 目标 3：我们将进行一项横断面研究，调查每个参与者的适应力、压力、社会功能、健康行为和生活质量指标，目的是确定可能影响镰状细胞病以及腿部溃疡形成和愈合的环境（即社会、身体和心理）因素。 目标 4：我们将进行基因组测序，以确定基因修饰剂在患有和不患有腿部溃疡的患者中的作用。具体来说，我们将对参与者进行全基因组测序，以研究导致患者群体腿部溃疡变异的遗传因素。 目标 5：我们将为 INSIGHTS 研究参与者制定和评估基因组结果返回计划。我们将进行一项人种学研究，收集纵向数据，以检查接收基因组学结果的研究参与者，并评估一段时间内的健康行为和治疗决策。 我们预测，在解决意外基因组结果方面最需要支持的研究参与者群体将是低收入和保险不足的个人。 目标：检查 COVID-19 大流行对镰状细胞病患者的影响 目标 6 和 7：我们将进行调查和访谈，以了解 COVID-19 大流行如何影响 SCD 患者，重点关注上述疾病的主要身体和心理社会方面，包括疼痛的表现、医疗保健利用以及社会和行为健康。我们特别感兴趣的是，在当前的大流行期间，疾病的严重程度、疼痛的频率和严重程度、医疗服务的频率和质量、情绪困扰、睡眠障碍、感知压力和恢复能力如何影响 SCD 患者的整体心理社会健康。