Prevalence of Thiamine Deficiency in Hospitalized Non-Alcoholic Veterans

背景：硫胺素缺乏症（TD）引起多种硫胺素缺乏症（TDDs），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。 如果不进行治疗，TD可能与生活质量差、丧失独立性和无法完成学业有关。 日常生活活动。TD在非酒精使用住院退伍军人中的患病率尚不清楚， 可能比一般人群高得多。功能丧失导致需要增加 康复活动. 本提案的目的是测量不过量使用TDDs的退伍军人的患病率。 酒精谁生病到需要住院治疗，确定炎症是否会增加发展的风险， TD，并确定TD的两个生物标志物诊断TDDs的最佳截止点。中央 假设TD患病率在住院的非酒精性退伍军人中高达25%，远高于 历史上报道的患病率为3%或更低，TDD发生在当前的“低正常”范围内， 可利用的硫胺素生物测定的截止值。第二个假设是， 已知会导致恶病质和营养不良，使住院的退伍军人面临更大的风险，因为他们经常 出现急性炎症。提出这项建议的基本理由是， 目前对TDDs诊断不足和治疗不足，这导致持续的发病率和功能丧失。如果我们的 假设是正确的，即患病率高达25%，这一知识将提高人们对 问题，并导致从业人员诊断和治疗他们更频繁。此外，澄清“非正常” 通过测量患有TDDs的退伍军人的“低”生物标志物截止水平是非常重要的， 在健康志愿者中确定“正常”范围。中心假设将通过追求三个测试 具体目标：1）确定TD的患病率，如全血和血浆硫胺素水平所定义 与不使用药物的连续住院患者的症状反应性疾病一起 过量饮酒; 2）将TDDs定义为低或“低正常”硫胺素水平和症状的病例， 补充硫胺素可改善病情; 3）确定急性和慢性炎症是否伴有升高的 炎症的生物标志物增加了发展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”生物标志物水平的低端也是如此。 低，缺少百分比的TDDs。 研究设计：为了实现这些目标，我们将采用前瞻性队列研究设计，以确定 TD在连续住院的非酒精性药物患者中的患病率，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。在此基础上，我们将进行 对表现出症状的患者进行开放标签治疗研究，并将TDDs定义为低或“正常值低”的病例 硫胺素水平和症状的TD改善与硫胺素管理。最后，利用嵌套的情况 对照研究设计，病例为TDD患者，对照为无症状退伍军人， 生物标志物，确定急性和慢性炎症性疾病是否具有升高的炎症生物标志物 增加发展TDDs的风险。 对退伍军人事务部使命的影响：确定不过量饮酒的退伍军人中TDDs的患病率 并要求住院将增加对这些情况的认识，提高诊断率 以及减轻后果的治疗这将解决一些退伍军人谁经历持久的 原发性疾病治疗后功能丧失，导致生活质量改善，独立性， 和功能这也可以通过改善他们对康复努力的反应来减少护理费用。

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.