Randomised trial of intravenous thiamine and/or magnesium sulphate administration on erythrocyte transketolase activity, lactate concentrations and alcohol withdrawal scores.

Alcohol withdrawal syndrome (AWS) occurs in 2% of patients admitted to U.K. hospitals. Routine treatment includes thiamine and benzodiazepines. Laboratory studies indicate that thiamine requires magnesium for optimal activity, however this has not translated into clinical practice. Patients experiencing AWS were randomized to three groups: (group 1) thiamine, (group 2) thiamine plus MgSO4 or (group 3) MgSO4. Pre- and 2-h post-treatment blood samples were taken. AWS severity was recorded using the Glasgow Modified Alcohol Withdrawal Score (GMAWS). The primary outcome measure was 15% change in erythrocyte transketolase activity (ETKA) in group 3. Secondary outcome measures were change in plasma lactate concentrations and time to GMAWS = 0. 127 patients were recruited, 115 patients were included in the intention-to-treat analysis. Pre-treatment, the majority of patients had normal or high erythrocyte thiamine diphosphate (TDP) concentrations (≥ 275-675/> 675 ng/gHb respectively) (99%), low serum magnesium concentrations (< 0.75 mmol/L) (59%), and high plasma lactate concentrations (> 2 mmol/L) (67%). Basal ETKA did not change significantly in groups 1, 2 or 3. Magnesium deficient patients (< 0.75 mmol/L) demonstrated less correlation between pre-treatment basal ETKA and TDP concentrations than normomagnesemic patients (R2 = 0.053 and R2 = 0.236). Median plasma lactate concentrations normalized (≤ 2.0 mmol/L) across all three groups (p < 0.001 for all groups), but not among magnesium deficient patients in group 1 (n = 22). The median time to achieve GMAWS = 0 for groups 1, 2 and 3 was 10, 5.5 and 6 h respectively (p < 0.001). No significant difference was found between groups for the primary endpoint of change in ETKA. Co-administration of thiamine and magnesium resulted in more consistent normalization of plasma lactate concentrations and reduced duration to achieve initial resolution of AWS symptoms.ClinicalTrials.gov: NCT03466528.

A prospective evaluation of thiamine and magnesium status in relation to clinicopathological characteristics and 1-year mortality in patients with alcohol withdrawal syndrome.

BACKGROUND: Alcohol withdrawal syndrome (AWS) is routinely treated with B-vitamins. However, the relationship between thiamine status and outcome is rarely examined. The aim of the present study was to examine the relationship between thiamine and magnesium status in patients with AWS. METHODS: Patients (n = 127) presenting to the Emergency Department with AWS were recruited to a prospective observational study. Blood samples were drawn to measure whole blood thiamine diphosphate (TDP) and serum magnesium concentrations. Routine biochemistry and haematology assays were also conducted. The Glasgow Modified Alcohol Withdrawal Score (GMAWS) measured severity of AWS. Seizure history and current medications were also recorded. RESULTS: The majority of patients (99%) had whole blood TDP concentration within/above the reference interval (275-675 ng/gHb) and had been prescribed thiamine (70%). In contrast, the majority of patients (60%) had low serum magnesium concentrations (< 0.75 mmol/L) and had not been prescribed magnesium (93%). The majority of patients (66%) had plasma lactate concentrations above 2.0 mmol/L. At 1 year, 13 patients with AWS had died giving a mortality rate of 11%. Male gender (p < 0.05), BMI < 20 kg/m2 (p < 0.01), GMAWS max ≥ 4 (p < 0.05), elevated plasma lactate (p < 0.01), low albumin (p < 0.05) and elevated serum CRP (p < 0.05) were associated with greater 1-year mortality. Also, low serum magnesium at time of recruitment to study and low serum magnesium at next admission were associated with higher 1-year mortality rates, (84% and 100% respectively; both p < 0.05). CONCLUSION: The prevalence of low circulating thiamine concentrations were rare and it was regularly prescribed in patients with AWS. In contrast, low serum magnesium concentrations were common and not prescribed. Low serum magnesium was associated more severe AWS and increased 1-year mortality.

Development, initial validation and reliability testing of a web-based, generic feline health-related quality-of-life instrument.

OBJECTIVES: The objective of this study was to develop a valid, reliable, web-based generic feline health-related quality-of-life (HRQoL) questionnaire instrument to measure the affective impact of chronic disease. METHODS: A large initial item pool, obtained through interviews with cat owners, was reduced using predetermined criteria, survey scores for relevance and clarity, and the ability of individual items to discriminate between healthy and sick cats when owners completed a prototype questionnaire. Using these data, factor analysis was used to derive a scoring algorithm and provide evidence for factorial validity. Validity was demonstrated further in a field trial using a 'known groups' approach (sick vs healthy cats will have a different HRQoL profile, and the HRQoL profile of cats will deteriorate as comorbidities increase). Test-retest reliability was assessed using intra-class correlation coefficients (ICCs). RESULTS: In total, 165 items were reduced to 20 and, on the basis of a factor analysis that explained 72.3% of the variation in scores input by 71 owners of 30 healthy and 41 sick cats using the prototype, these were allocated to three domains (vitality, comfort and emotional wellbeing [EWB]) with a scoring algorithm derived using item loadings. Subsequently, the owners of 36 healthy and 58 sick cats completed one or two (n = 48) assessments. Median scores (healthy vs sick) for all domains were significantly different ( P <0.001), 78% of cats were correctly classified as healthy or sick and for comorbidities the correlation coefficients were moderate (vitality 0.64; comfort 0.63; EWB 0.50). Test-retest reliability was good (ICC vitality 0.635; comfort 0.716; EWB 0.853). CONCLUSIONS AND RELEVANCE: This study provides initial evidence for the validity and reliability of a novel HRQoL instrument to aid the assessment and management of chronic diseases of cats.

Cytogenetics in pediatric low-grade astrocytomas.

BACKGROUND: Cytogenetic analysis in certain tumors is a vital part of classification and assignment of prognosis. Few studies have examined the value of cytogenetic analysis in pediatric brain tumors. This is especially true of low-grade astrocytomas (LGA) of childhood. This study examines the correlation between cytogenetic abnormalities and survival in children with low-grade astrocytomas. The literature on adults with LGA suggest better survival for those whose tumors have normal cytogenetics compared to those with abnormal. We hypothesized this would also be true of children with low-grade astrocytomas. PROCEDURE: A retrospective study was performed of children presenting between 1980 and 1998 to The Children's Hospital, Denver, who had LGA and on whose tumors informative cytogenetics had obtained. RESULTS: One hundred and forty-nine children were diagnosed with histologically proven LGA. Twenty-nine had successful cytogenetic analysis. One or more chromosomal abnormalities were observed in eight tumors while normal karyotypes were observed in 21 tumors. Actuarial progression-free survival at 5 years was 87.5% for the eight children with abnormal cytogenetics and 43% for those with normal (P=0.56). Overall survival at 5 years was 83% for those with abnormal cytogenetics and 78% for those with normal (P=0.8). The differences in progression-free survival and overall survival between these two groups were not significant. Those children with WHO Grade I tumors had significantly superior progression-free and overall survival than those with Grade II tumors. CONCLUSIONS: It appears unlikely that, for children with LGA, those with normal cytogenetics have a better prognosis than those with abnormal. Histologic grade is a better predictor of outcome than cytogenetics.