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Principal Investigator: Elisabeth Mates
Organization: VA SIERRA NEVADA HEALTH CARE SYSTEM
Fiscal Year: 2024
Funding agency: Veterans Affairs
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.
Terms: <Activities of Daily Living><Activities of everyday life><Acute><Address><Affective Disorders><Alcohol Chemical Class><Alcohols><Aneurin><Assay><Ataxia><Ataxy><Autopsy><Awareness><Beri Beri><Beriberi><Bioassay><Biological Assay><Biological Markers><Blood><Blood Plasma><Blood Reticuloendothelial System><COVID-19 infection><COVID-19 virus infection><COVID19 infection><Cachectic><Cachexia><Caring><Categories><Causality><Cerebral Beriberi><Chronic><Chronic Disease><Chronic Illness><Chronically Ill><Clinical><Confusion><Confusional State><Coordination Impairment><Country><Debility><Diagnosis><Diagnostic Findings><Dialysis><Dialysis procedure><Diarrhea><Diet Habits><Dietary Habits><Disease><Disorder><Diuretics><Dyssynergia><Economic Income><Economical Income><Economics><Elderly><Emesis><Encephalopathies><Etiology><Exhibits><Face><Fatigue><Food><Gayet-Wernicke Encephalopathy><General Population><General Public><Goals><Groups at risk><Health><Heart failure><High Prevalence><Hospital Admission><Hospitalists><Hospitalization><Hospitals><Hypertension><Incidence><Income><Individual><Inflammation><Inflammatory><Intake><Kidney Failure><Kidney Insufficiency><Knowledge><LMIC><Laboratories><Lack of Energy><Lead><Left><Leg><Malabsorption Syndromes><Malnutrition><Measures><Medical><Medical Rehabilitation><Medicine><Mental Confusion><Metabolic><Mission><Mood Disorders><Morbidity><Morbidity - disease rate><Nervous System Physiology><Nested Case-Control Study><Neurologic><Neurologic function><Neurological><Neurological function><Normal Range><Normal Values><Nutrient><Nutritional Deficiency><Outcome><Oxidative Stress><Patient Admission><Patients><Pb element><People at risk><Persons at risk><Plasma><Plasma Serum><Polyneuropathy><Population><Populations at Risk><Predisposing Factor><Predisposition><Prevalence><Probability><Prospective, cohort study><Publishing><QOL><Quality of life><Rehabilitation><Rehabilitation therapy><Renal Failure><Renal Insufficiency><Reporting><Research Design><Reticuloendothelial System, Serum, Plasma><Risk><Risk Factors><SARS-CoV-2 infection><SARS-CoV2 infection><Sepsis><Severe acute respiratory syndrome coronavirus 2 infection><Signs and Symptoms><Stress><Study Type><Susceptibility><Swelling><Symptoms><Syndrome><Testing><Thiamine><Thiamine Deficiency><Time><Toxin><Undernutrition><United States><Vascular Hypertensive Disease><Vascular Hypertensive Disorder><Veterans><Vit B1><Vitamin B 1><Vitamin B1><Vitamins><Vomiting><Wernicke Encephalopathy><Wernicke Syndrome><Wernicke's Disease><Wernicke's Superior Hemorrhagic Polioencephalitis><Whole Blood><advanced age><after stroke><alcohol abuser><bio-markers><biologic marker><biomarker><blood infection><bloodstream infection><cardiac failure><care costs><causation><chronic disorder><clinical relevance><clinically relevant><cofactor><coronavirus disease 2019 infection><daily living function><daily living functionality><dialysis therapy><dietary deficiency><disease causation><eating habit><economic><experience><faces><facial><falls><food insecurity><functional ability><functional capacity><functional loss><gastrointestinal><gastrointestinal absorption disorder><geriatric><healthy volunteer><heavy metal Pb><heavy metal lead><high blood pressure><hyperpiesia><hyperpiesis><hypertensive disease><hypertensive disorder><improve symptom><improved><incomes><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><intestinal malabsorption><life-threatening COVID><life-threatening COVID-19><life-threatening SARS-CoV-2><life-threatening coronavirus disease><life-threatening coronavirus disease 2019><life-threatening severe acute respiratory syndrome coronavirus 2><loss of function><low and middle-income countries><malabsorption><malnourished><micronutrient deficiency><necropsy><nervous system function><neuropsychiatric><neuropsychiatry><non-alcoholic><nonalcoholic><nutrition deficiency><nutrition deficiency disorder><nutritional deficiency disorder><open label><open label study><post stroke><postmortem><poststroke><rehab therapy><rehabilitative><rehabilitative therapy><response><senior citizen><serious COVID><serious COVID-19><serious SARS-CoV-2><serious coronavirus disease><serious coronavirus disease 2019><serious severe acute respiratory syndrome coronavirus 2><severe COVID><severe COVID-19><severe COVID19><severe SARS-CoV-2><severe coronavirus disease><severe coronavirus disease 19><severe coronavirus disease 2019><severe severe acute respiratory syndrome coronavirus 2><social><study design><symptom improvement><symptomatic improvement><thiamin><treatment planning>