Efficacy and Safety of Hydrocortisone, Ascorbic Acid, and Thiamine Combination Therapy for the Management of Sepsis and Septic Shock: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

INTRODUCTION: This systematic review aimed to assess the efficacy and safety of hydrocortisone, ascorbic acid, and thiamine (HAT) combination therapy in patients with sepsis and septic shock. METHODS: We conducted a database search in MEDLINE, Embase, CENTRAL, Web of Science, and CNKI for randomised controlled trials (RCTs) comparing HAT against placebo/standard of care or against hydrocortisone in sepsis/septic shock patients. Outcomes included mortality, ICU/hospital length of stay (LOS), vasopressor durations, mechanical ventilation durations, change in SOFA at 72 h, and adverse events. RCT results were pooled in random-effects meta-analyses. Quality of evidence was assessed using GRADE. RESULTS: Fifteen RCTs (N = 2,594) were included. At 72 h, HAT reduced SOFA scores from baseline (mean difference [MD] -1.16, 95% confidence interval [CI]: -1.58 to -0.74, I2 = 0%) compared to placebo/SoC, based on moderate quality of evidence. HAT also reduced the duration of vasopressor use (MD -18.80 h, 95% CI: -23.67 to -13.93, I2 = 64%) compared to placebo/SoC, based on moderate quality of evidence. HAT increased hospital LOS (MD 2.05 days, 95% CI: 0.15-3.95, I2 = 57%) compared to placebo/SoC, based on very low quality of evidence. HAT did not increase incidence of adverse events compared to placebo/SoC. CONCLUSIONS: HAT appears beneficial in reducing vasopressor use and improving organ function in sepsis/septic shock patients. However, its advantages over hydrocortisone alone remain unclear. Future research should use hydrocortisone comparators and distinguish between sepsis-specific and comorbidity- or care-withdrawal-related mortality.

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.

[A CASE OF ANAPHYLAXIS INDUCED BY VITAMIN B1 DERIVATIVE IN VITAMIN B INFUSION FORMULATION FOR INTRAVENOUS INJECTION].

A woman in her 20s presented to our clinic with a lower gastrointestinal infection. When we administered intravenous antibacterial and vitamin infusions, she developed anaphylaxis. We performed skin tests to investigate the cause, and an intradermal test was positive for a 1% intravenous vitamin complex. We then performed a component-specific test, which was positive for thiamine disulfide phosphate, a vitamin B1 derivative. We therefore diagnosed anaphylaxis due to thiamine disulfide phosphate. No previous reports have described cross-reactivity between vitamin B1 derivatives. In our case, however, the patient tested positive for fluthiamine hydrochloride, suggesting cross-reactivity. Intravenous vitamin complexes are used in daily clinical practice and should be administered with caution because of the possibility of anaphylaxis, although it occurs infrequently.

Furosemide-related thiamine deficiency in hospitalized hypervolemic patients with renal failure and heart failure.

BACKGROUND: We aimed to describe the thiamine status in hospitalized hypervolemic heart failure (HF) and/or renal failure (RF) patients treated with furosemide and to investigate whether there was a difference in furosemide-related thiamine deficiency between patients with RF and HF. METHODS: Patients who were diagnosed as hypervolemia and treated with intravenous furosemide (at least 40mg/day) were included in this prospective observational study. Whole blood thiamine concentrations were measured 3 times during hospital follow-up of patients. RESULTS: We evaluated 61 hospitalized hypervolemic patients, of which 22 (36%) were men and 39 (64%) were women, with a mean age of 69.00±10.39 (45-90) years. The baseline and post-hospital admission days 2 and 4 mean thiamine levels were 51.71±20.66ng/ml, 47.64±15.43ng/ml and 43.78±16.20ng/ml, respectively. Thiamine levels of the hypervolemic patients decreased significantly during the hospital stay while furosemide treatment was continuing (p=0.029). There was a significant decrease in thiamine levels in patients who had HF (p=0.026) and also, thiamine was significantly lower in HF patients who had previously used oral furosemide before hospitalization. However, these findings were not present in patients with RF. CONCLUSIONS: Thiamine substantially decreases in most hypervolemic patients receiving intravenous furosemide treatment during the hospital stay. Thiamine levels were significantly decreased with furosemide treatment in especially HF patients, but the decrease in thiamine levels did not detected at the same rate in RF patients. Diuretic-induced thiamine loss may be less likely in RF patients, probably due to a reduction in excretion.

Unanswered questions on the use of hydrocortisone, ascorbic acid, and thiamine therapy in sepsis and septic shock.

PURPOSE: To evaluate current evidence on the utility of hydrocortisone, ascorbic acid, and thiamine (HAT) therapy for the management of septic shock. SUMMARY: The following keyword search terms were utilized in PubMed to identify relevant articles: ascorbic acid, thiamine, hydrocortisone, shock, and critical care. Articles relevant to HAT therapy in patients with septic shock were selected. Retrospective cohorts and randomized controlled trials were included in this review; case reports/series were excluded. Data from included studies illustrating the use of HAT therapy for the management of sepsis and septic shock, including data on time to HAT therapy initiation, severity of illness at baseline, duration of vasopressor therapy, progression of organ failure, and mortality, were evaluated. CONCLUSION: The utilization of HAT therapy for the management of sepsis and septic shock remains controversial. Hemodynamic benefits have been shown to be most pronounced when HAT therapy is initiated earlier. Future studies directed at earlier initiation may be necessary to confirm this theory.

Evaluation of the safety of 500 mg intravenous push thiamine at a tertiary academic medical center.

Background: Thiamine, also known as vitamin B1, is an essential water-soluble micronutrient. Although thiamine has minimal safety concerns, parenteral administration has been associated with rare cases of anaphylactic shock, cardiac arrest, and injection site reaction. The objective of this analysis is to evaluate the incidence of anaphylaxis and injection site reactions associated with the administration of thiamine 500 mg as an intravenous (IV) push in adult patients. Method: This single-center, retrospective analysis was performed at Brigham and Women's Hospital in Boston, Massachusetts. Electronic health records were used to identify all adult patients who were ordered for thiamine 500 mg IV push between July 1, 2020, and December 31, 2020. For the major and minor endpoints, anaphylaxis and injection site reactions were assessed, respectively. Descriptive statistics were used as appropriate. Results: A total of 463 doses of thiamine in 69 patients were evaluated. Thiamine was administered peripherally for 392 (84.7%) doses and centrally for 68 (14.7) doses. No anaphylactic reactions were observed. A total of 4 injection site reactions (0.86%) were noted with 4 unique doses. All reactions were classified as low-grade based on our institutional grading system. All injection site reactions were classified as "possible" (Naranjo score of 1-4). Conclusion: Administration of IV push 500 mg thiamine was not associated with anaphylactic events and was associated with a low rate of injection site reactions.

Evaluation of the Safety of Intravenous Thiamine Administration in a Large Academic Medical Center.

BACKGROUND/OBJECTIVE: Previous literature describes increased incidence of infusion-related reactions when administering thiamine doses greater than 100 mg as an intravenous (IV) push. The purpose of this evaluation was to assess the safety of administering higher doses of thiamine as IV push compared to infusion. METHODS: A single-center, retrospective review was performed from June to October 2017. Included patients were aged 18 years or older and received 1 dose of IV thiamine 200 mg or greater. Patients were divided into 2 groups: group 1 included patients who received 200-mg IV push and, group 2 included patients who received any dose greater than 200 mg. The primary objective was to quantify and compare rate of adverse reactions between the 2 groups. Institutional thiamine prescribing practices were examined. Wilcoxon Rank Sum and Fischer exact tests were performed. RESULTS: Sixty-six percent of patients were male, and the median age was 55 years (interquartile range [IQR]: 44-63). Fifty percent received 200-mg IV push, 20% received a combination of IV infusion and IV push, and 30% received IV infusion. Adverse reactions possibly due to thiamine administration occurred in 4 (2.0%) patients. One patient received 200 mg via IV infusion, while 3 received 200 mg via IV push. There was no significant difference in adverse reaction rate between IV push and IV infusion administrations (P = .640). CONCLUSION: Our results support administering thiamine doses of 200 mg or less as an IV push. Given lack of robust safety data, it is recommended to continue to dilute doses greater than 200 mg and infuse over 30 minutes.

Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Organ Injury in Septic Shock: The ACTS Randomized Clinical Trial.

IMPORTANCE: The combination of ascorbic acid, corticosteroids, and thiamine has been identified as a potential therapy for septic shock. OBJECTIVE: To determine whether the combination of ascorbic acid, corticosteroids, and thiamine attenuates organ injury in patients with septic shock. DESIGN, SETTING, AND PARTICIPANTS: Randomized, blinded, multicenter clinical trial of ascorbic acid, corticosteroids, and thiamine vs placebo for adult patients with septic shock. Two hundred five patients were enrolled between February 9, 2018, and October 27, 2019, at 14 centers in the United States. Follow-up continued until November 26, 2019. INTERVENTIONS: Patients were randomly assigned to receive parenteral ascorbic acid (1500 mg), hydrocortisone (50 mg), and thiamine (100 mg) every 6 hours for 4 days (n = 103) or placebo in matching volumes at the same time points (n = 102). MAIN OUTCOMES AND MEASURES: The primary outcome was change in the Sequential Organ Failure Assessment (SOFA) score (range, 0-24; 0 = best) between enrollment and 72 hours. Key secondary outcomes included kidney failure and 30-day mortality. Patients who received at least 1 dose of study drug were included in analyses. RESULTS: Among 205 randomized patients (mean age, 68 [SD, 15] years; 90 [44%] women), 200 (98%) received at least 1 dose of study drug, completed the trial, and were included in the analyses (101 with intervention and 99 with placebo group). Overall, there was no statistically significant interaction between time and treatment group with regard to SOFA score over the 72 hours after enrollment (mean SOFA score change from 9.1 to 4.4 [-4.7] points with intervention vs 9.2 to 5.1 [-4.1] points with placebo; adjusted mean difference, -0.8; 95% CI, -1.7 to 0.2; P = .12 for interaction). There was no statistically significant difference in the incidence of kidney failure (31.7% with intervention vs 27.3% with placebo; adjusted risk difference, 0.03; 95% CI, -0.1 to 0.2; P = .58) or in 30-day mortality (34.7% vs 29.3%, respectively; hazard ratio, 1.3; 95% CI, 0.8-2.2; P = .26). The most common serious adverse events were hyperglycemia (12 patients with intervention and 7 patients with placebo), hypernatremia (11 and 7 patients, respectively), and new hospital-acquired infection (13 and 12 patients, respectively). CONCLUSIONS AND RELEVANCE: In patients with septic shock, the combination of ascorbic acid, corticosteroids, and thiamine, compared with placebo, did not result in a statistically significant reduction in SOFA score during the first 72 hours after enrollment. These data do not support routine use of this combination therapy for patients with septic shock. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03389555.

Safety of intravenous push thiamine administration at a tertiary academic medical center.

OBJECTIVES: Intravenous (IV) thiamine, administered using both diluted solution for infusion and undiluted solution for IV push, is used to correct low levels of thiamine. Although thiamine has a good safety profile, its IV administration is associated with rare cases of anaphylaxis. The objective of this analysis was to evaluate the incidence of anaphylaxis and IV site reactions associated with IV push thiamine. DESIGN: A single-center, retrospective chart review was performed using electronic health records. SETTING AND PARTICIPANTS: All adult patients who received undiluted IV push thiamine between June 1, 2015, and July 31, 2017, were included. Patient demographics, IV access site, allergy history, and antihistaminic medication use before thiamine administration were collected. OUTCOME MEASURES: Anaphylaxis was assessed while infiltration and phlebitis were evaluated using a standardized institutional grading system. All documented adverse events were adjudicated with the Naranjo Nomogram for adverse drug reaction assessment. RESULTS: A total of 8606 administrations in 2595 patients were evaluated; 5560 doses were administered peripherally, 1643 doses were administered centrally, and the line of administration was not documented for the remaining doses. Administrations included 7605 doses of 100 mg, 433 of 200 mg, 549 of 250 mg, and 19 of 500 mg. No anaphylactic or anaphylactoid reactions were observed. A total of 26 injection site reactions (0.30%) were noted in 19 patients (phlebitis, 12 events and infiltration, 14 events). Assessment with the Naranjo Nomogram classified 18 reactions to have a possible likelihood and 8 reactions to have a probable likelihood of being caused by IV push thiamine administration. CONCLUSION: Administration of IV push thiamine was not associated with any anaphylactic event and had a low incidence of IV site reactions. IV push thiamine in doses up to 250 mg appeared to be safe. There may be an indication for its safe administration with doses up to 500 mg, although more research is needed.

Administration of Corticosteroids, Ascorbic Acid, and Thiamine Improves Oxygenation after Thoracoscopic Esophagectomy.

PURPOSE: The activity of corticosteroids, ascorbic acid, and thiamine against oxidative and inflammatory responses was evaluated in patients undergoing esophagectomy. This study was undertaken to investigate the effect of this combined therapy on lung dysfunction following esophagectomy. METHODS: In this retrospective before-after study, we compared the clinical course of consecutive patients undergoing thoracoscopic esophagectomy treated with the combination of corticosteroids, ascorbic acid, and thiamine between June and December 2018 with a control group treated with corticosteroids alone between January 2016 and May 2018. Outcomes included oxygenation (arterial partial pressure of oxygen (PaO2)/fractional concentration of inspired oxygen (FiO2) ratios), duration of mechanical ventilation and intensive care unit (ICU) length of stay. RESULTS: In all, 17 patients were included in this study (6 in the combination therapy group and 11 patients in the control group). Mean PaO2/FiO2 ratios in the combined therapy group were significantly higher than in the control group at all points during the observation period (p <0.001). In the combined therapy group, the duration of mechanical ventilation and ICU stay were significantly shorter (p <0.001, p = 0.009). CONCLUSIONS: This study suggests that combined therapy including corticosteroids, ascorbic acid, and thiamine may be effective in improving oxygenation after esophagectomy. Additional studies are required to confirm these preliminary findings.

Incidence of Adverse Reactions to Parenteral Thiamine in the Treatment of Wernicke's Encephalopathy, and Recommendations.

AIM: To offer an estimate of the incidence of anaphylactic reactions to parenteral products containing thiamine used in the treatment of Wernicke's encephalopathy (WE) and make recommendations. METHOD: Review of previously released data on some older products and parenteral thiamine use in some other countries; analysis of sales and adverse incident data on anaphylaxis for a contemporary parenteral product used in the UK, Pabrinex. RESULTS: It was difficult to estimate the incidence of related anaphylactic reactions to Pabrinex in the UK because the number of doses given is unknown. Sales data are only an approximation to doses given because for products with a limited shelf life not all product sold is administered. However, available data indicate that there have been 10 anaphylactic reactions to Pabrinex from between 5,431,235-6,651,947 patient-days (14,880-16,080 years) of treatment. CONCLUSION: It is reasonable to assume that the risk of anaphylaxis is low, and lower than for many other drugs. The risk-benefit ratio for administration is favourable given the potential severity of brain damage in Wernicke-Korsakoff (WK) syndrome. There is a need for international agreement on the reporting of anaphylaxis and on the optimum thiamine therapy for the treatment of WK syndrome. We make recommendations on how this might be achieved.

Mechanisms of Non-coenzyme Action of Thiamine: Protein Targets and Medical Significance.

Thiamine (vitamin B1) is a precursor of the well-known coenzyme of central metabolic pathways thiamine diphosphate (ThDP). Highly intense glucose oxidation in the brain requires ThDP-dependent enzymes, which determines the critical significance of thiamine for neuronal functions. However, thiamine can also act through the non-coenzyme mechanisms. The well-known facilitation of acetylcholinergic neurotransmission upon the thiamine and acetylcholine co-release into the synaptic cleft has been supported by the discovery of thiamine triphosphate (ThTP)-dependent phosphorylation of the acetylcholine receptor-associated protein rapsyn, and thiamine interaction with the TAS2R1 receptor, resulting in the activation of synaptic ion currents. The non-coenzyme regulatory binding of thiamine compounds has been demonstrated for the transcriptional regulator p53, poly(ADP-ribose) polymerase, prion protein PRNP, and a number of key metabolic enzymes that do not use ThDP as a coenzyme. The accumulated data indicate that the molecular mechanisms of the neurotropic action of thiamine are far broader than it has been originally believed, and closely linked to the metabolism of thiamine and its derivatives in animals. The significance of this topic has been illustrated by the recently established competition between thiamine and the antidiabetic drug metformin for common transporters, which can be the reason for the thiamine deficiency underlying metformin side effects. Here, we also discuss the medical implications of the research on thiamine, including the role of thiaminases in thiamine reutilization and biosynthesis of thiamine antagonists; molecular mechanisms of action of natural and synthetic thiamine antagonists, and biotransformation of pharmacological forms of thiamine. Given the wide medical application of thiamine and its synthetic forms, these aspects are of high importance for medicine and pharmacology, including the therapy of neurodegenerative diseases.

Combination therapy of vitamin C and thiamine for septic shock in a multicentre, double-blind, randomized, controlled study (ATESS): study protocol for a randomized controlled trial.

BACKGROUND: Septic shock is a life-threatening condition with underlying circulatory and cellular/metabolic abnormalities. Vitamin C and thiamine are potential candidates for adjunctive therapy; they are expected to improve outcomes based on recent experimental and clinical research. The aim of the Ascorbic Acid and Thiamine Effect in Septic Shock (ATESS) trial is to evaluate the effects of early combination therapy with intravenous vitamin C and thiamine on recovery from organ failure in patients with septic shock. METHODS: This study is a randomized, double-blind, placebo-controlled, multicentre trial in adult patients with septic shock recruited from six emergency departments in South Korea. Patients will be randomly allocated into the treatment or control group (1:1 ratio), and we will recruit 116 septic shock patients (58 per group). For the treatment group, vitamin C (50 mg/kg) and thiamine (200 mg) will be mixed in 50 ml of 0.9% saline and administered intravenously every 12 h for a total of 48 h. For the placebo group, an identical volume of 0.9% saline will be administered in the same manner. The primary outcome is the delta Sequential Organ Failure Assessment (SOFA) score (ΔSOFA = initial SOFA at enrolment - follow-up SOFA after 72 h). DISCUSSION: This trial will provide valuable evidence about the effectiveness of vitamin C and thiamine therapy for septic shock. If effective, this therapy might improve survival and become one of the main therapeutic adjuncts for patients with septic shock. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03756220 . Registered on 5 December 2018.

The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) Protocol: a prospective, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial.

BACKGROUND: Sepsis accounts for 30% to 50% of all in-hospital deaths in the United States. Other than antibiotics and source control, management strategies are largely supportive with fluid resuscitation and respiratory, renal, and circulatory support. Intravenous vitamin C in conjunction with thiamine and hydrocortisone has recently been suggested to improve outcomes in patients with sepsis in a single-center before-and-after study. However, before this therapeutic strategy is adopted, a rigorous assessment of its efficacy is needed. METHODS: The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) trial is a prospective, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled trial. It will enroll patients with sepsis causing respiratory or circulatory compromise or both. Patients will be randomly assigned (1:1) to receive intravenous vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) every 6 h or matching placebos until a total of 16 administrations have been completed or intensive care unit discharge occurs (whichever is first). Patients randomly assigned to the comparator group are permitted to receive open-label stress-dose steroids at the discretion of the treating clinical team. The primary outcome is consecutive days free of ventilator and vasopressor support (VVFDs) in the 30 days following randomization. The key secondary outcome is mortality at 30 days. Sample size will be determined adaptively by using interim analyses with pre-stated stopping rules to allow the early recognition of a large mortality benefit if one exists and to refocus on the more sensitive outcome of VVFDs if an early large mortality benefit is not observed. DISCUSSION: VICTAS is a large, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled trial that will test the efficacy of vitamin C, thiamine, and hydrocortisone as a combined therapy in patients with respiratory or circulatory dysfunction (or both) resulting from sepsis. Because the components of this therapy are inexpensive and readily available and have very favorable risk profiles, demonstrated efficacy would have immediate implications for the management of sepsis worldwide. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03509350 . First registered on April 26, 2018, and last verified on December 20, 2018. Protocol version: 1.4, January 9, 2019.

The role of thiamine dependent enzymes in obesity and obesity related chronic disease states: A systematic review.

The WHO 2016 report indicates that worldwide obesity is rising, with over 600 million people in the obese range (BMI>30). The recommended daily calorie intake for adults is 2000 kcal and 2500 kcal for women and men respectively. The average American consumes 3770 kcal/day and the average person in the UK consumes 3400 kcal/day. With such increased caloric intake, there is an increased load on metabolic pathways, in particular glucose metabolism. Such metabolism requires micronutrients as enzyme co-factors. The recommended daily allowance (RDA) for thiamine is 1.3 mg/day and 0.5 mg thiamine is required to process 1000 kilocalories (kcal). Therefore, despite the appearance of being overfed, there is now increasing evidence that the obese population may nutritionally depleted of essential micronutrients. Thiamine deficiency has been reported to be in the region of 16-47% among patients undergoing bariatric surgery for obesity. Thiamine, in turn, requires magnesium to be in its active form thiamine diphosphate, (TDP). TDP also requires magnesium to achieve activation of TDP dependent enzymes, including transketolase (TK), pyruvate dehydrogenase (PDH) and alpha-keto glutaric acid dehydrogenase (AKGDH), during metabolism of glucose. Thiamine and magnesium therefore play a critical role in glucose metabolism and their deficiency may result in the accumulation of anaerobic metabolites including lactate due to a mismatch between caloric burden and function of thiamine dependent enzymes. It may therefore be postulated that thiamine and magnesium deficiency are under-recognized in obesity and may be important in the progress of obesity and obesity related chronic disease states. The aim of the present systematic review was to examine the role of thiamine dependent enzymes in obesity and obesity related chronic disease states.

[Evaluation of efficiency and safety of adding neuromultivit to basic therapy of vertebrogenic radiculopathy]. / Éffektivnost' i bezopasnost' neiromul'tivita pri vertebrogennykh radikulopatiiakh.

AIM: To evaluate the efficacy and safety of neuromultivit (valiant, Russia) as add-on to the basic therapy of vertebrogenic radiculopathy (VR) L5-S1. MATERIAL AND METHODS: The open clinical trial included 100 patients with VR L5-S1 randomized into 2 groups. In group 1, patients received neuromultivit and basic therapy; in group 2 only basic therapy. Treatment efficacy was assessed by the dynamics of regression of pain intensity on the visual analogue scale (VAS), McGill pain questionnaire (MGPQ), Aberdeen back pain scale (ABPS), the Quebec Back Pain Disability Scale (QBPDS), the dynamics of neurologic symptoms, the need for additional treatment with NSAID. Safety was assessed by evaluation of vital functions, laboratory tests, ECG, registration of adverse events (AE). RESULTS: In both groups, a significant positive changes on VAS, MGPQ, ABPS, QBPDS were observed. Nevertheless, the positive effect of therapy was more pronounced in group 1 p<0.05). The AE spectrum between two groups did not differ significantly (p<0.05). CONCLUSION: Addition of neuromultivit to basic therapy increased the efficacy of treatment of VR L5-S1.

Thiamine, cobalamin, locally injected alone or combination for herpetic itching: a single-center randomized controlled trial.

OBJECTIVES: The present study was designed to explore the efficacy of locally injected thiamine or cobalamin in relieving itch or pain and improving the daily living activities among patients with herpetic itching. METHODS: Eighty eligible patients with herpetic itching with a worst itching score of ≥ 4 were randomized to receive locally injected thiamine (B1 group), cobalamin (B12 group), lidocaine (LD group), or combination of thiamine and cobalamin (COB group) for 4 weeks. The treatment efficacy was assessed based on the patients' pruritus and pain severity, global impression of change, and activities of daily living and quality of life. RESULTS: After 7 days, thiamine yielded a significant itch relief, cobalamin yielded a significant pain relief, and their combination significantly relieved both pain and itch; which all continued till the endpoint (all Ps<0.001). However, lidocaine did not provide significant itch or pain relief than the other groups. Sixteen patients in the thiamine group achieved ≥ 30% itch reduction; 18 patients in the cobalamin group obtained ≥ 30% pain reduction; and 18 patients achieved ≥ 30% itch reduction and 19 patients obtained ≥ 30% pain reduction in the combination group. The activities of daily living and quality of life data at the endpoint were consistent with a significant benefit in the thiamine (P<0.05), cobalamin, and combination groups (both Ps<0.001). DISCUSSION: Locally injected thiamine had a significant antipruritic effect, cobalamin had an analgesic effect, and their combination had the dual effect with no obvious synergies. This intervention was efficacious, tolerable, and safe for herpetic itching.