Prevalence of Thiamine Deficiency in Hospitalized Non-Alcoholic Veterans

住院非酗酒退伍军人硫胺素缺乏症的患病率

• 批准号: 10655567
• 负责人: Elisabeth Mates
• 金额: --
• 依托单位: VA SIERRA NEVADA HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10655567
• 关键词: Activities of Daily Living; Acute; Address; Alcohols; Ataxia; Autopsy; Awareness; Biological Assay; Biological Markers; Blood; Cachexia; Caring; Categories; Chronic; Chronic Disease; Chronically Ill; Clinical; Confusion; Country; Diagnosis; Dialysis procedure; Diarrhea; Diet Habits; Disease; Diuretics; Economics; Elderly; Encephalopathies; Etiology; Exhibits; Face; Fatigue; Food; General Population; Goals; Health; Heart failure; High Prevalence; Hospitalists; Hospitalization; Hospitals; Hypertension; Incidence; Income; Individual; Inflammation; Inflammatory; Intake; Kidney Failure; Knowledge; Laboratories; Lead; Left; Leg; Malabsorption Syndromes; Malnutrition; Measures; Medical; Medicine; Metabolic; Mission; Mood Disorders; Morbidity - disease rate; Nervous System Physiology; Nested Case-Control Study; Neurologic; Normal Range; Nutrient; Outcome; Oxidative Stress; Patient Admission; Patients; Plasma; Polyneuropathy; Population; Populations at Risk; Predisposing Factor; Predisposition; Prevalence; Probability; Prospective, cohort study; Publishing; Quality of life; Rehabilitation therapy; Reporting; Research Design; Risk; Risk Factors; SARS-CoV-2 infection; Sepsis; Signs and Symptoms; Stress; Swelling; Symptoms; Syndrome; Testing; Thiamine; Thiamine Deficiency; Time; Toxin; United States; Veterans; Vitamins; Vomiting; Wernicke Encephalopathy; Whole Blood; alcohol abuser; care costs; clinically relevant; cofactor; experience; falls; food insecurity; functional loss; gastrointestinal; healthy volunteer; improved; loss of function; low and middle-income countries; micronutrient deficiency; neuropsychiatry; non-alcoholic; open label; post stroke; response; severe COVID-19; social; symptomatic improvement; treatment planning

Background: Thiamine deficiency (TD) causes a variety of thiamine deficiency disorders (TDDs) such as neuropsychiatric disturbances, polyneuropathy, ataxia, weakness and falling, and non-ischemic heart failure. Left untreated, TD can be associated with poor quality of life, loss of independence, and inability to complete activities of daily living. The prevalence of TD in non-alcohol using hospitalized Veterans is not known but is probably much higher than the general population. Loss of functional ability leads to increased need for rehabilitation. The objective of this proposal is to measure the prevalence of TDDs in Veterans who do not use excess alcohol who are ill enough to require hospitalization, determine if inflammation increases the risk of developing TD, and determine the optimal cutoff points for two biomarkers of TD to diagnose of TDDs. The central hypothesis is that TD prevalence is as high as 25% in hospitalized non-alcoholic Veterans, far greater than the historically reported prevalence of 3% or less, and that TDD’s occur in the “low normal” range of current cutoff values for available thiamine bioassays. A secondary hypothesis is that inflammatory conditions, which are known to cause cachexia and malnutrition, put hospitalized Veterans at increased risk as they often present with acute inflammatory conditions. The rationale underlying this proposal is that hospital practitioners currently underdiagnose and undertreat TDDs which leads to continued morbidity and loss of function. If our hypothesis is correct that the prevalence is as high as 25%, this knowledge will increase awareness of the problem and lead practitioners to diagnose and treat them more often. In addition, clarifying the “abnormally low” biomarker cutoff levels by measuring them in Veterans with TDDs is very important as the current “normal” ranges were determined in healthy volunteers. The central hypothesis will be tested by pursuing three specific aims: 1) determine the prevalence of TD, as defined by whole blood and plasma thiamine levels together with symptom responsive disease in consecutively hospitalized medicine patients who do not use excessive alcohol; 2) define TDDs as cases with low or “low normal” thiamine levels and symptoms that improve with thiamine replenishment; 3) determine if acute and chronic inflammatory conditions with elevated biomarkers of inflammation increase the risk of developing TDD. We expect to find the prevalence of TD is closer to 25% and that the low end of “normal” biomarker levels as published by reference laboratories is too low, missing a percentage of TDDs. Research design: To accomplish these aims, we will utilize a prospective cohort study design to determine the prevalence of TD in consecutively hospitalized non-alcoholic medicine patients, as defined by low or “low normal” thiamine biomarker levels and thiamine responsive symptoms. Nested within this we will conduct an open label treatment study with those exhibiting symptoms and define TDDs as cases with low or “low normal” thiamine levels and symptoms of TD that improve with thiamine administration. Lastly, utilizing a nested case control study design with cases being those with a TDD and controls being asymptomatic Veterans with normal biomarkers, determine if acute and chronic inflammatory conditions with elevated biomarkers of inflammation increase the risk of developing TDDs. Impact to the VA mission: Determining the prevalence of TDDs in Veterans who don’t use excessive alcohol and require hospital admission will increase awareness of these conditions and improve the rate of diagnosis and treatment to mitigate the consequences. This would address some Veterans who experience persistent loss of function after the primary condition has been treated leading to improved quality of life, independence, and function. This could also reduce the cost of care by improving their response to rehabilitation efforts.

背景：硫胺素缺乏 (TD) 会导致多种硫胺素缺乏症 (TDD)，例如 神经精神障碍、多发性神经病、共济失调、虚弱和跌倒以及非缺血性心力衰竭。 如果不及时治疗，TD 可能会导致生活质量差、丧失独立性和无法完成任务 住院退伍军人中不酗酒的 TD 患病率尚不清楚，但确实存在。 可能远高于一般人群的功能能力丧失导致对药物的需求增加。 康复。 该提案的目的是衡量不使用过多药物的退伍军人中 TDD 的患病率 对于病情严重需要住院治疗的饮酒者，确定炎症是否会增加患病风险 TD，并确定 TD 的两种生物标志物诊断 TDD 的最佳截止点。 假设住院的非酗酒退伍军人中 TD 患病率高达 25%，远高于 历史报告的患病率为 3% 或更低，并且 TDD 发生在当前的“低正常”范围内 可用硫胺素生物测定的临界值第二个假设是炎症状况。 已知会导致恶病质和营养不良，使住院退伍军人面临更大的风险，因为他们经常 该建议的基本原理是医院医生患有急性炎症。 目前，TDD 的诊断和治疗不足，导致持续发病和功能丧失。 流行率高达 25% 的假设是正确的，这一知识将提高人们对这一疾病的认识 并引导医生更经常地诊断和治疗他们，此外，澄清“异常”。 通过在患有 TDD 的退伍军人中测量“低”生物标志物截止水平非常重要，因为当前 “正常”范围是在健康志愿者中确定的，中心假设将通过三个方面进行检验。 具体目标：1) 根据全血和血浆硫胺素水平确定 TD 的患病率 与连续住院药物但不使用药物的患者发生症状反应性疾病 2) 将 TDD 定义为硫胺素水平低或“正常水平低”且出现下列症状的病例： 补充硫胺素可改善；3) 确定急性和慢性炎症状况是否升高； 炎症的生物标志物会增加患 TDD 的风险，我们预计 TD 的患病率是 接近 25%，参考实验室公布的“正常”生物标志物水平的下限也太低 低，缺少一定比例的 TDD。 研究设计：为了实现这些目标，我们将利用前瞻性队列研究设计来确定 连续住院的非酒精药物患者的 TD 患病率，定义为低或“低” 正常的”硫胺素生物标志物水平和硫胺素反应症状在此范围内，我们将进行一项检查。 对那些表现出症状的人进行开放标签治疗研究，并将 TDD 定义为低或“低正常”病例 服用硫胺素可改善硫胺素水平和 TD 症状 最后，利用嵌套案例。 对照研究设计，病例为 TDD 患者，对照为无症状退伍军人，且病情正常 生物标志物，确定炎症生物标志物是否升高的急性和慢性炎症状况 增加开发 TDD 的风险。 对退伍军人事务部使命的影响：确定不过度饮酒的退伍军人中 TDD 的患病率 并要求住院将提高对这些情况的认识并提高诊断率 以及减轻后果的治疗，这将解决一些经历持续的退伍军人的问题。 原发疾病治疗后功能丧失，生活质量、独立性、 这还可以通过改善他们对康复工作的反应来降低护理成本。