Prevalence of Thiamine Deficiency in Hospitalized Non-Alcoholic Veterans

背景：硫胺素缺乏症(TD)可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任务有关 日常生活活动。住院退伍军人中非酒精性精神障碍的患病率尚不清楚，但 可能比一般人要高得多。功能能力的丧失导致对 康复。 这项建议的目的是测量不使用过量药物的退伍军人中TDDS的患病率 酗酒者病情严重需要住院，确定炎症是否会增加发病风险 中环 假设在住院的非酒精性退伍军人中TD患病率高达25%，远远高于 可用硫胺素生物测定的截止值。第二个假设是炎症条件，这是 出现急性炎症状态。这项建议背后的理由是，医院从业者 目前对TDDS的诊断和治疗不足，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 并引导从业者更频繁地诊断和治疗这些问题。此外，澄清“非正常” 在患有TDDS的退伍军人中，通过测量生物标志物的低截止水平非常重要，因为目前 健康志愿者的“正常”范围被确定。核心假设将通过追求三个方面来检验 具体目标：1)根据全血和血浆硫胺素水平确定TD的患病率 连续住院的不使用药物的患者合并症状反应性疾病 过量饮酒；2)将TDDS定义为硫胺素水平低或“低正常”的病例，症状为 通过补充硫胺素改善；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生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记物水平的低端也是 低，缺少一定百分比的TDDS。 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 连续住院的非酒精类药物患者中TD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。嵌套在其中的我们将进行一个 对有症状的患者进行开放标签治疗研究，并将TDDS定义为低或“低正常”病例 硫胺素水平和TD症状随着硫胺素的应用而改善。最后，利用嵌套案例 生物标志物，确定急性和慢性炎症条件下炎症生物标志物是否升高 增加了罹患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 并要求入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。这将解决一些退伍军人的问题，他们经历了 原发病治疗后功能丧失，导致生活质量提高，独立性， 和功能。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。

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.