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：硫胺素缺乏症（TD）引起多种硫胺素缺乏障碍（TDD），例如 神经精神灾难，多神经病，共济失调，无力和下降以及非缺血性心力衰竭。 剩下的未治疗，TD可能与生活质量差，独立性丧失以及无法完成有关 日常生活的活动。使用住院的退伍军人在非酒精中的TD患病率尚不清楚，但IS 可能比一般人口高得多。功能能力的丧失导致对 康复。 该提案的目的是衡量不使用不使用的退伍军人中TDD的患病率 足以需要住院的酒精，确定炎症是否增加了发展的风险 TD，并确定两个TD生物标志物的最佳截止点以诊断TDD。中央 假设是TD患病率高达住院的非酒精老兵25％，远远大于 历史上报告的患病率为3％或以下，而TDD发生在“低正常”电流范围内 可用硫胺生物测定的截止值。次要假设是炎症条件， 众所周知会导致病原体和营养不良，使住院的退伍军人处于增加的风险，因为他们经常 存在急性炎症条件。该提议的基本原理是医院医生 目前，诊断不足的TDD和未经处理的TDD导致持续发病和功能丧失。如果我们 假设是正确的，即患病率高达25％，这种知识将提高人们对 问题并导致从业人员更频繁地诊断和对待他们。另外，澄清“异常 低“生物标志物截止水平通过在具有TDD的退伍军人中测量它们非常重要，因为电流非常重要 在健康志愿者中确定“正常”范围。中心假设将通过追求三个 具体目的：1）确定TD的患病率，如全血和血浆硫胺素水平所定义 连续住院的药物患者的症状反应性疾病，不使用 过多的酒精； 2）将TDD定义为低或“低正常”硫胺素水平和符号的病例 通过硫胺素补充改善； 3）确定急性和慢性炎症条件是否升高 炎症的生物标志物增加了发展TDD的风险。我们希望发现TD的流行是 参考实验室发布的“正常”生物标志物水平的低端也接近25％ 低，缺少TDD的百分比。 研究设计：为了实现这些目标，我们将利用潜在的队列研究设计来确定 不断住院的非酒精药物患者TD的患病率是低或低的“ 正常”硫胺素生物标志物水平和硫胺素反应症状。在此内嵌套 用那些表现出符号并将TDD定义为低或“低正常”的病例的开放标签治疗研究 硫胺素给药的硫胺素水平和TD的症状。最后，使用嵌套的情况 对照研究设计的案例是患有TDD的病例，对照是不对称的退伍军人 生物标志物，确定急性和慢性炎症条件是否具有炎症的生物标志物升高 增加开发TDD的风险。 对VA任务的影响：确定不使用多余酒精的退伍军人中TDD的患病率 并需要住院入院将提高对这些状况的认识并提高诊断率 和治疗以减轻后果。这将解决一些经历持久的退伍军人 主要状况后的功能丧失已得到治疗，从而改善了生活质量，独立性， 和功能。这也可以通过改善他们对康复工作的反应来降低护理成本。