A Randomized Control Trial of Dexketoprofen/Vitamin B (Thiamine, Pyridoxine and Cyanocobalamin) Fixed-Dose Combination in Post-Traumatic Grade I-II Cervical Sprains.

BACKGROUND: Musculoskeletal disorders are an important cause of work absence. Clinical practice guidelines recommend nonsteroidal anti-inflammatory drugs (NSAIDs) for grade I-II cervical sprains. The combination of thiamine + pyridoxine + cyanocobalamin vitamins has been used, alone and in combination with NSAIDs, for pain and inflammation in musculoskeletal disorders. OBJECTIVE: The objective of this study was to demonstrate the analgesic synergy of dexketoprofen, and the combination of vitamins thiamine + pyridoxine + cyanocobalamin in a fixed-dose combination (FDC) for the treatment of acute pain caused by grade I-II cervical sprains. METHODS: We conducted a multicentre, prospective, randomized, double-blind, phase IIIb clinical study comparing two treatment groups: (1) dexketoprofen 25 mg/vitamin B (thiamine 100 mg, pyridoxine 50 mg and cyanocobalamin 0.50 mg) in an FDC (two or more active ingredients combined in a single dosage form) versus (2) dexketoprofen 25 mg monotherapy (single drug to treat a particular disease), one capsule or tablet orally, every 8 h for 7 days. Final mean, average change, and percentage change in pain perception (measured using a visual analogue scale [VAS]) were compared with baseline between groups. A p value < 0.05 was considered statistically significant. Analyses were conducted using SPSS software, v.29.0. RESULTS: A statistically significant reduction in pain intensity was observed from the third day of treatment with the FDC compared with monotherapy (- 3.1 ± - 1.5 and - 2.6 ± - 1.1 cm, respectively) measured using the VAS (p = 0.011). Regarding the degree of disability, using the Northwick Park Neck Pain Questionnaire (NPQ), statistical difference was observed for the final measurement (7.5%, interquartile range [IQR] 2.5, 10.5; vs. 7.9%, IQR 5.0, 13.8; p = 0.028). A lower proportion of adverse events was reported when using the FDC. CONCLUSIONS: The FDC of dexketoprofen/thiamine + pyridoxine + cyanocobalamin vitamins demonstrated superior efficacy and a better safety profile compared with dexketoprofen monotherapy for pain treatment in patients with grade I-II cervical sprains. CLINICAL TRIALS REGISTRATION: NCT05001555, registered 29 July 2021 ( https://clinicaltrials.gov/study/NCT05001555 ).

Role of Thiamine Supplementation in the Treatment of Chronic Heart Failure: An Updated Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Chronic heart failure (CHF) has always posed a significant threat to human survival and health. The efficacy of thiamine supplementation in CHF patients remains uncertain. HYPOTHESIS: Receiving supplementary thiamine may not confer benefits to patients with CHF. METHODS: A comprehensive search was conducted across the Cochrane Library, PubMed, EMBASE, ClinicalTrials.gov, and Web of Science databases up until May 2023 to identify articles investigating the effects of thiamine supplementation in CHF patients. Predefined criteria were utilized for selecting data on study characteristics and results. RESULTS: Seven randomized, double-blind, controlled trials (five parallel trials and two crossover trials) involving a total of 274 patients were enrolled. The results of the meta-analysis pooling these studies did not reveal any significant effect of thiamine treatment compared with placebo on left ventricular ejection fraction (WMD = 1.653%, 95% CI:  -1.098 to 4.405, p = 0.239, I2 = 61.8%), left ventricular end-diastolic volume (WMD = -6.831 mL, 95% CI:  -26.367 to 12.704, p = 0.493, I2 = 0.0%), 6-min walking test (WMD = 16.526 m, 95% CI:  -36.582 to 69.634, p = 0.542, I2 = 66.3%), N-terminal pro-B type natriuretic peptide (WMD = 258.150 pg/mL, 95% CI:  -236.406 to 752.707, p = 0.306, I2 = 21.6%), or New York Heart Association class (WMD = -0.223, 95% CI:  -0.781 to 0.335, p = 0.434, I2 = 87.1%). However, it effectively improved the status of thiamine deficiency (TD). CONCLUSIONS: Our meta-analysis indicates that thiamine supplementation does not have a direct therapeutic effect on CHF, except for correcting TD.

Visual loss and encephalopathy in a pregnant patient with hyperemesis gravidarum.

A pregnant woman in her 20s at 17 weeks of gestation, presented with symptoms of painless diminution of vision preceded by 8 weeks history of hyperemesis gravidarum. On examination, she was confused, disoriented and had gait ataxia with complete loss of vision in both eyes. Fundus examination revealed grade 4 disc oedema with superficial retinal haemorrhages. Possibilities kept were cerebral venous sinus thrombosis, neuromyelitis optica spectrum disorder, posterior reversible encephalopathy syndrome and Wernicke's encephalopathy (WE). Thiamine levels were low. MRI brain with MR venography revealed symmetrical areas of hyperintensities in bilateral medial thalami, hypothalamus, mammillary body and area postrema. She was managed as a case of WE with intravenous thiamine with complete clinical and radiological resolution within 2 weeks of treatment. Therefore, we conclude that a high index of suspicion of WE in appropriate clinical settings leading to early treatment can potentially reverse its grave clinical symptoms and complications.

Neurologic complications of thiamine (B1) deficiency following bariatric surgery in adolescents.

BACKGROUND: The prevalence of obesity among children and adolescents is rising and poses a major health concern. Bariatric surgery is well established in adults and has become an option for adolescents. Thiamine (B1) deficiency is common following bariatric surgery in adults. It may present as Beri-Beri, Wernicke encephalopathy, or Korsakoff psychosis. OBJECTIVE: Our aim was to describe the clinical features, diagnosis, and treatment of adolescents who presented with B1 deficiency after bariatric surgery at one center, and to summarize the data from the literature. PATIENTS: Three adolescents with morbid obesity (two boys and one girl, aged 15.5 to- 17-years-old), presented at Schneider Children's Medical Center of Israel with progressive lower limb pain and weakness 2-3 month following a bariatric procedure (sleeve gastrectomy or narrowing of a bariatric band). The girl also had upper limb involvement and cerebellar signs. All three were non-compliant with micronutrient supplementation. After admission, they received intravenous B1 and oral multivitamin supplementation, and their symptoms improved considerably. CONCLUSIONS: Micronutrient supplementation following bariatric surgery is crucial to prevent deficiencies. In adolescents, compliance with micronutrient supplementation should be assessed before and after such surgery. Thiamine deficiency may cause polyneuropathy, among other symptoms. Treatment reduces the severity of neurological complications.

Protocol for a seamless phase 2A-phase 2B randomized double-blind placebo-controlled trial to evaluate the safety and efficacy of benfotiamine in patients with early Alzheimer's disease (BenfoTeam).

BACKGROUND: Benfotiamine provides an important novel therapeutic direction in Alzheimer's disease (AD) with possible additive or synergistic effects to amyloid targeting therapeutic approaches. OBJECTIVE: To conduct a seamless phase 2A-2B proof of concept trial investigating tolerability, safety, and efficacy of benfotiamine, a prodrug of thiamine, as a first-in-class small molecule oral treatment for early AD. METHODS: This is the protocol for a randomized, double-blind, placebo-controlled 72-week clinical trial of benfotiamine in 406 participants with early AD. Phase 2A determines the highest safe and well-tolerated dose of benfotiamine to be carried forward to phase 2B. During phase 2A, real-time monitoring of pre-defined safety stopping criteria in the first approximately 150 enrollees will help determine which dose (600 mg or 1200 mg) will be carried forward into phase 2B. The phase 2A primary analysis will test whether the rate of tolerability events (TEs) is unacceptably high in the high-dose arm compared to placebo. The primary safety endpoint in phase 2A is the rate of TEs compared between active and placebo arms, at each dose. The completion of phase 2A will seamlessly transition to phase 2B without pausing or stopping the trial. Phase 2B will assess efficacy and longer-term safety of benfotiamine in a larger group of participants through 72 weeks of treatment, at the selected dose. The co-primary efficacy endpoints in phase 2B are CDR-Sum of Boxes and ADAS-Cog13. Secondary endpoints include safety and tolerability measures; pharmacokinetic measures of thiamine and its esters, erythrocyte transketolase activity as blood markers of efficacy of drug delivery; ADCS-ADL-MCI; and MoCA. CONCLUSION: The BenfoTeam trial utilizes an innovative seamless phase 2A-2B design to achieve proof of concept. It includes an adaptive dose decision rule, thus optimizing exposure to the highest and best-tolerated dose. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06223360, registered on January 25, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT06223360.

Long-Term Maintenance of Normal Serum Vitamin B1 Levels Is Associated with Better Outcomes in Patients with Heart Failure.

Deficiency of vitamin B1 (VB1), an essential micronutrient, causes heart failure (HF). A recent randomized controlled trial failed to show any improvement in HF prognosis after short-term VB1 supplementation. In the current study, we investigated the efficacy of long-term maintenance of normal blood VB1 levels in preventing adverse outcomes in patients with HF.This study included 88 consecutive patients with HF who received guideline-directed medical therapy at Arida Municipal Hospital. The patients were divided into 3 groups: a control group with normal VB1 levels and no VB1 supplementation (normal group, n = 25), and those presenting with VB1 deficiency, who either required short-term VB1 supplementation (short-term supplementation group, n = 25), or long-term maintenance of normal blood VB1 levels (long-term maintenance group, n = 38). The time to the first appearance of composite outcomes, including cardiovascular death and hospitalization for HF, was compared between the 3 groups.VB1 deficiency was observed in 63 (72%) patients. The Kaplan-Meier curve showed that the long-term maintenance group had better outcomes than the other 2 groups. In the multivariate analysis, long-term maintenance of normal blood VB1 levels and age were independent predictors of composite outcomes.VB1 deficiency is frequently observed, and the long-term maintenance of normal blood VB1 levels may result in better outcomes in patients with HF. Our results suggest that the detection of VB1 deficiency and long-term restoration of VB1 levels may be part of the overall therapeutic strategy for HF.

Vitamin B1 Deficiency Identified from Incidental Detection of Hyperlactatemia: A Case Report.

Introduction: Vitamin B1 deficiency poses a significant risk of impaired consciousness, with manifestations ranging from anorexia and fatigue to severe neurological and cardiovascular disturbances. Wernicke's encephalopathy, a neurological disorder stemming from vitamin B1 deficiency, presents as the triad of ophthalmoplegia, altered mental state, and cerebellar ataxia. However, these symptoms are not consistently present, complicating the diagnosis. In addition, subclinical vitamin B1 deficiency can progress unnoticed until severe complications arise. Studies indicate a high rate of undiagnosed cases, emphasizing the need for early detection and intervention. Case presentation: We present the case of a 65-year-old man in whom hyperlactatemia was incidentally detected, leading to the diagnosis of vitamin B1 deficiency. The patient, presenting with vertigo and vomiting, had been eating boxed lunches bought from convenience stores following the death of his wife 3 years earlier. Vertigo gradually improved with rest, but the persistence of hyperlactatemia prompted further investigation, revealing low vitamin B1 levels and high pyruvate levels. Treatment with dietary adjustments and supplements significantly improved his symptoms. Discussion: In this case, hyperlactatemia was found in a vertigo patient, revealing asymptomatic vitamin B1 deficiency. Elevated lactate is often linked with conditions like sepsis but can also stem from overlooked factors such as low vitamin B1 levels due to poor diet habits like consuming fried foods. Conclusion: This case highlights the importance of considering vitamin B1 deficiency in patients with unexplained hyperlactatemia, even in high-income countries. Early detection can prevent progression to the severe complications associated with Wernicke's encephalopathy. Proactive measurement of lactate levels in at-risk populations may facilitate early diagnosis and intervention, ultimately improving patient outcomes.

Wernicke Encephalopathy After Roux-en-Y Gastric Bypass Presenting with Altered Mental Status-A Video Case Report.

Wernicke encephalopathy (WE) is a seldom encountered yet significant neuropsychiatric ailment resulting from a deficiency in thiamine (vitamin B1). While commonly linked with chronic alcoholism or insufficient dietary intake, instances of WE following bariatric and metabolic surgeries, notably laparoscopic Roux-en-Y gastric bypass (RYGB), have been sporadically documented. This case study elucidates the condition of a male patient who, 3 months after undergoing RYGB to address severe obesity, displayed abrupt alterations in mental status, swiftly ameliorated by immediate administration of intravenous high-dose thiamine.

Thiamine as a metabolic resuscitator after out-of-hospital cardiac arrest.

INTRODUCTION: Thiamine is a key cofactor for aerobic metabolism, previously shown to improve mortality and neurological outcomes in a mouse model of cardiac arrest. We hypothesized that thiamine would decrease lactate and improve outcomes in post-arrest patients. METHODS: Single center, randomized, blinded, placebo-controlled, Phase II trial of thiamine in adults within 4.5 hours of return of spontaneous circulation after out-of-hospital cardiac arrest (OHCA), with coma and lactate ≥ 3 mmol/L. Participants received 500 mg IV thiamine or placebo twice daily for 2 days. Randomization was stratified by lactate > 5 or ≤ 5 mmol/L. The primary outcome of lactate was checked at baseline, 6, 12, and 24 hours, and compared using a linear mixed model to account for repeated measures. Secondary outcomes included SOFA score, pyruvate dehydrogenase, renal injury, neurological outcome, and mortality. RESULTS: Of 93 randomized patients, 76 were enrolled and included in the analysis. There was no difference in lactate over 24 hours (mean difference 0.34 mmol/L (95% CI: -1.82, 2.50), p = 0.43). There was a significant interaction between randomization lactate subgroup and the effect of the intervention on mortality (p = 0.01) such that mortality was higher with thiamine in the lactate > 5 mmol/L group and lower with thiamine in the < 5 mmol/L group. This subgroup difference prompted the Data and Safety Monitoring Board to recommend the study be terminated early. PDH activity increased over 72 hours in the thiamine group. There were no differences in other secondary outcomes. CONCLUSION: In this single-center randomized trial, thiamine did not affect lactate over 24 hours after OHCA.

Thiamine as a metabolic resuscitator after in-hospital cardiac arrest.

INTRODUCTION: Elevated lactate is associated with mortality after cardiac arrest. Thiamine, a cofactor of pyruvate dehydrogenase, is necessary for aerobic metabolism. In a mouse model of cardiac arrest, thiamine improved pyruvate dehydrogenase activity, survival and neurologic outcome. AIM: To determine if thiamine would decrease lactate and increase oxygen consumption after in-hospital cardiac arrest. METHODS: Randomized, double-blind, placebo-controlled phase II trial. Adult patients with arrest within 12 hours, mechanically ventilated, with lactate ≥ 3 mmol/L were included. Randomization was stratified by lactate > 5 or ≤ 5 mmol/L. Thiamine 500 mg or placebo was administered every 12 hours for 3 days. The primary outcome of lactate was checked at baseline, 6, 12, 24, and 48 hours, and compared using a linear mixed model, accounting for repeated measures. Secondary outcomes included oxygen consumption, pyruvate dehydrogenase, and mortality. RESULTS: Enrollments stopped after 36 patients due Data Safety and Monitoring Board concern about potential harm in an unplanned subgroup analysis. There was no overall difference in lactate (mean difference at 48 hours 1.5 mmol/L [95% CI -3.1-6.1], global p = 0.88) or any secondary outcomes. In those with randomization lactate > 5 mmol/L, mortality was 92% (11/12) with thiamine and 67% (8/12) with placebo (p = 0.32). In those with randomization lactate ≤ 5 mmol/L mortality was 17% (1/6) with thiamine and 67% (4/6) with placebo (p = 0.24). There was a significant interaction between randomization lactate and the effect of thiamine on survival (p = 0.03). CONCLUSIONS: In this single center trial thiamine had no overall effect on lactate after in-hospital cardiac arrest.

High-dose oral thiamine versus placebo for chronic fatigue in patients with primary biliary cholangitis: A crossover randomized clinical trial.

BACKGROUND & AIMS: Fatigue has high negative impact on many patients with primary biliary cholangitis (PBC) and treatment options are limited. Recently we showed favorable effects of four weeks of high-dose thiamine treatment on fatigue in patients with inflammatory bowel disease. We aimed to investigate the effect and safety of high-dose (600-1800 mg daily) oral thiamine treatment on chronic fatigue in patients with PBC. METHODS: Randomized, double-blinded, placebo-controlled crossover trial including patients with severe PBC-related fatigue. Participants were allocated 1:1 to either group 1) 4 weeks of high-dose thiamine, 4 weeks of washout, and 4 weeks of placebo; or group 2) 4 weeks of placebo, washout, and high-dose thiamine, respectively. Fatigue severity was quantified using the fatigue subscale of the PBC-40 questionnaire. The primary outcome was a fatigue reduction of ≥ 5 points after 4 weeks of high-dose thiamine treatment. RESULTS: We enrolled 36 patients; 34 completed the study. The overall mean reduction in fatigue was 5.0 points (95% CI: 2.5 to 7.5; p < 0.001) for the combined group 1 and group 2. Crossover analysis showed a mean increase in fatigue of 0.3 points (95% CI: -4.2 to 3.8) after high-dose thiamine treatment compared to a 1.4 points (95% CI: 6.2 to -3.4) mean reduction after placebo (p = 0.55). Only mild and transient adverse events were recorded. CONCLUSION: Four weeks of high-dose oral thiamine treatment in patients with PBC was well tolerated and safe. However, high-dose thiamine was not superior to placebo in reducing PBC-related fatigue. TRIAL REGISTRATION: The trial was registered in the ClinicalTrials.gov (NCT04893993) and EudraCT (2020-004935-26).

Use of Thiamine Supplementation in Pregnant Women Diagnosed With Hyperemesis Gravidarum and Wernicke Encephalopathy.

Hyperemesis gravidarum is the most common condition requiring hospital care for women during the first 20 weeks of pregnancy and may lead to malnutrition, dehydration, and vitamin deficiencies. Depletion of vitamins such as thiamine may result in the development of Wernicke encephalopathy, a severe neurological disorder that can increase the risk for mortality and morbidity for the mother and fetus. A lack of awareness regarding the relationship of hyperemesis gravidarum and Wernicke encephalopathy may result in delayed treatment and disease management. Glucose administration in the presence of thiamine deficiency may induce Wernicke encephalopathy; protocols are needed to ensure dextrose is used for women with hyperemesis gravidarum in times of prolonged vomiting and poor oral intake only after first administering thiamine. This article includes a discussion of best practices for thiamine supplementation with hyperemesis gravidarum and Wernicke encephalopathy.

Presentation of Wernicke encephalopathy in patient secondary to one anastomosis gastric bypass. Case report and literature review.

Wernicke encephalopathy, which is caused by a thiamine deficiency, occurs in 0.8-2% of the population. Only 16% present the typical triad of this disease: nystagmus, confusion and ataxia. We present the case of a postoperative patient with a one anastomosis gastric bypass with reoperation undergoing a Roux-en-Y gastric bypass that begins with confusion and nystagmus on her third postoperative day. The diagnosis of Wernicke encephalopathy is made by imaging, and vitamin B1 is administered with total improvement of nystagmus and altered state of consciousness (lethargy, bradypsychia, bradylalia).

La encefalopatía de Wernicke se produce por una deficiencia de tiamina se presenta en un 0.8-2% de la población. Solo el 16% de los casos presentan la tríada típica de esta enfermedad: nistagmo, confusión y ataxia. Presentamos el caso de una paciente operada de bypass gástrico de una anastomosis con reintervención convirtiendo a bypass gástrico en Y de Roux que en su tercer día de posoperatorio comienza con confusión y nistagmo. Se realiza por imagen el diagnóstico de encefalopatía de Wernicke se administra vitamina B1 con mejoría total del nistagmo y alteración del estado de consciencia (letargia, bradipsiquia, bradilalia).

Clinical Features and Outcomes of Shoshin Beriberi.

Shoshin beriberi is a fulminant form of wet beriberi, but there are no large-scale studies detailing the clinical features of this disease. We investigated the clinical features and outcomes of Shoshin beriberi using data from a nationwide database in Japan.Using the Diagnosis Procedure Combination database, we identified patients with Shoshin beriberi between July 2010 and March 2021. We retrospectively investigated the characteristics, comorbidities, treatment, and in-hospital mortality of patients with Shoshin beriberi. The chi-square test or Fisher's exact test was used for categorical variables, and the Mann-Whitney U-test was used for continuous variables.We identified 62 patients with Shoshin beriberi. The median (interquartile range) age was 63 (48-69) years. Furthermore, 54 patients were male (87%). The most common comorbidity was alcohol-related disorder (34%). The median (interquartile range) length of hospital and intensive care unit stays were 17 (range, 10-35) and 5 (range, 1-9) days, respectively. The proportion of patients who received venoarterial extracorporeal membrane oxygenation, intra-aortic balloon pump, continuous renal replacement therapy, and mechanical ventilation was 11, 5, 29, and 63%, respectively. Among the patients with Shoshin beriberi, 53% received 2 or more catecholamines or inotropes. The in-hospital mortality was 23%. Impaired consciousness at admission was significantly related to in-hospital death (P < 0.001).The present study is the first and largest to describe the clinical features of patients with Shoshin beriberi using a nationwide database. Impaired consciousness at admission was significantly associated with in-hospital death.

Diagnosis and treatment of Wernicke's encephalopathy: A systematic literature review.

BACKGROUND: Wernicke's encephalopathy (WE) is a serious neurological disorder that is underdiagnosed. Despite limited clinical guidelines, the standard use of intravenous (IV) thiamine is underutilized and remains an area of research deserving much attention. OBJECTIVES: We conducted a systematic review using Medline, Embase, and CENTRAL databases to identify and summarize the literature on IV thiamine treatment in WE. Human studies with WE patients who received ≥100 mg of thiamine IV met inclusion criteria. Randomized controlled trials, cross-sectional studies, and case reports were included. RESULTS: A total of 27 studies were included: 20 case reports, five retrospective studies, one prospective study and one randomized control trial. Of the case reports, 11 (55%) cases were female, and the average age of all cases was 45 years (SD = 15). The other seven studies included 688 patients; the average age was 52 years (SD = 9), and 266 (38.7%) were female. Among the case reports, neurological and clinical findings were used to diagnose WE in 16 (80%) cases. MRI was utilized to diagnose 15 (75%) cases. 500 mg IV thiamine TID was reported in 12 case reports (60%). 18 (90%) of case reports had partial or complete resolution of symptoms following IV thiamine. CONCLUSION: IV thiamine can alleviate neurological symptoms, cognitive dysfunction, and brain imaging lesions associated with WE. We found key limitations in the evidence for IV thiamine and diagnostic standards for WE. Future targeted research should establish clear diagnostic and treatment guidelines for WE to prevent this serious condition from being underdiagnosed or undertreated.

Thiamine administration in septic shock: a post hoc analysis of two randomized trials.

BACKGROUND: This is a post hoc analysis of combined cohorts from two previous Phase II clinical trials to assess the effect of thiamine administration on kidney protection and mortality in patients with septic shock. METHODS: Patient-level data from the Thiamine in Septic Shock Trial (NCT01070810) and the Thiamine for Renal Protection in Septic Shock Trial (NCT03550794) were combined in this analysis. The primary outcome for the current study was survival without the receipt of renal replacement therapy (RRT). Analyses were performed on the overall cohort and the thiamine-deficient cohort (thiamine < 8 nmol/L). RESULTS: Totally, 158 patients were included. Overall, thiamine administration was associated with higher odds of being alive and RRT-free (adjusted odds ratio [aOR]: 2.05 [95% confidence interval (CI) 1.08-3.90]) and not needing RRT (aOR: 2.59 [95% CI 1.01-6.62]). In the thiamine-deficient group, thiamine administration was associated with higher odds of being alive and RRT-free (aOR: 8.17 [95% CI 1.79-37.22]) and surviving to hospital discharge (aOR: 6.84 [95% CI 1.54-30.36]). There was a significant effect modification by baseline thiamine deficiency for alive and RRT-free (interaction, p = 0.016) and surviving to hospital discharge (p = 0.019). CONCLUSION: In the combined analysis of two previous randomized trials, thiamine administration was associated with higher odds of being alive and RRT-free at hospital discharge in patients with septic shock. This signal was stronger in patients with thiamine deficiency.

Thiamine as adjunctive therapy for diabetic ketoacidosis (DKAT) trial protocol and statistical analysis plan: a prospective, single-centre, double-blind, randomised, placebo-controlled clinical trial in the USA.

INTRODUCTION: Diabetic ketoacidosis (DKA) is a potentially life-threatening diabetic complication. Despite the high prevalence of DKA and the substantial associated healthcare burden, limited research on strategies to improve outcomes currently exists.Thiamine (vitamin B1) is a cofactor of pyruvate dehydrogenase, which plays a key role in aerobic glucose metabolism. Thiamine deficiency is common in patients with DKA, resulting in a shift to anaerobic metabolism and hyperlactatemia, which can prolong and complicate recovery. Therefore, we hypothesise that thiamine administration will improve aerobic metabolism and lead to faster resolution of acidemia in patients with DKA. METHODS AND ANALYSIS: In this single centre, double-blind, randomised, placebo-controlled, parallel group interventional trial, 100 patients admitted to the hospital with DKA will be randomised to receive either intravenous thiamine (200 mg in 50 mL 0.9% saline) or placebo (0.9% saline identical in appearance and volume) two times per day for 2 days. The primary outcome will be the change in bicarbonate level over 24 hours as compared between the two treatment groups. Additional secondary outcomes include the change over time in anion gap, lactate levels, oxygen consumption by circulating mononuclear cells, intensive care unit and hospital length-of-stay and hospital resource usage when comparing the two study arms. ETHICS AND DISSEMINATION: This trial was approved by the Committee on Clinical Investigations, the institutional review board of Beth Israel Deaconess Medical Center (protocol number 2018P000475). Findings will be disseminated through peer-reviewed publications and professional conference presentations. TRIAL REGISTRATION NUMBER: NCT03717896; clinicaltrials.gov.

A Predictive Model for Thiamine Responsive Disorders Among Infants and Young Children: Results from a Prospective Cohort Study in Lao People's Democratic Republic.

OBJECTIVE: To develop a predictive model for thiamine responsive disorders (TRDs) among infants and young children hospitalized with signs or symptoms suggestive of thiamine deficiency disorders (TDDs) based on response to therapeutic thiamine in a high-risk setting. STUDY DESIGN: Children aged 21 days to <18 months hospitalized with signs or symptoms suggestive of TDD in northern Lao People's Democratic Republic were treated with parenteral thiamine (100 mg daily) for ≥3 days in addition to routine care. Physical examinations and recovery assessments were conducted frequently for 72 hours after thiamine was initiated. Individual case reports were independently reviewed by three pediatricians who assigned a TRD status (TRD or non-TRD), which served as the dependent variable in logistic regression models to identify predictors of TRD. Model performance was quantified by empirical area under the receiver operating characteristic curve. RESULTS: A total of 449 children (median [Q1, Q3] 2.9 [1.7, 5.7] months old; 70.3% exclusively/predominantly breastfed) were enrolled; 60.8% had a TRD. Among 52 candidate variables, those most predictive of TRD were exclusive/predominant breastfeeding, hoarse voice/loss of voice, cyanosis, no eye contact, and no diarrhea in the previous 2 weeks. The area under the receiver operating characteristic curve (95% CI) was 0.82 (0.78, 0.86). CONCLUSIONS: In this study, the majority of children with signs or symptoms of TDD responded favorably to thiamine. While five specific features were predictive of TRD, the high prevalence of TRD suggests that thiamine should be administered to all infants and children presenting with any signs or symptoms consistent with TDD in similar high-risk settings. The usefulness of the predictive model in other contexts warrants further exploration and refinement. TRIAL REGISTRATION: Clinicaltrials.gov NCT03626337.