Prevalence of biotin supplement usage in outpatients and plasma biotin concentrations in patients presenting to the emergency department.

BACKGROUND: Several cases of biotin interference with laboratory testing have been reported in the literature. However, there are no publications discussing the extent of biotin use or plasma concentrations observed among the patient population. The objective of this study was to determine the prevalence of biotin consumption using two distinct methods: surveying the outpatient population using a questionnaire and quantifying biotin in plasma samples collected from patients presenting to the Emergency Department (ED). METHODS: Survey questionnaires (n = 4000) were distributed to Mayo Clinic outpatients over one week (July 10-14, 2017). Biotin was quantified in residual waste plasma samples collected for physician-ordered electrolyte panels from patients presenting to the ED (March 6-12, 2017 and March 26-April 4, 2017, n = 1442 unique patient samples). RESULTS: 1944 patients (972 female, 963 male, 9 no answer) with a median (interquartile range) age of 62 (49-72) years returned completed questionnaires (48.6%). From the completed surveys, 7.7% (95% CI, 6.6-8.9%) indicated biotin use. Quantitation of biotin in plasma samples from ED patients (n = 1442) revealed that 7.4% (95% CI, 6.2-8.9%) had concentrations at or above the lowest known threshold (10 ng/mL) for biotin interference in Roche Diagnostics immunoassay tests. CONCLUSIONS: According to our survey results, reported use of biotin was common. The range of biotin concentrations in ED patient samples highlights the magnitude of the biotin interference problem and identifies a population at risk for potential harm. These findings should guide laboratorians and clinicians in developing effective strategies to mitigate safety risks and in assessing biotin usage trends within their own patient populations.

Effects of Rifaximin on Transit, Permeability, Fecal Microbiome, and Organic Acid Excretion in Irritable Bowel Syndrome.

OBJECTIVES: Rifaximin relieves irritable bowel syndrome (IBS) symptoms, bloating, abdominal pain, and loose or watery stools. Our objective was to investigate digestive functions in rifaximin-treated IBS patients. METHODS: In a randomized, double-blind, placebo-controlled, parallel-group study, we compared the effects of rifaximin, 550 mg t.i.d., and placebo for 14 days in nonconstipated IBS and no evidence of small intestinal bacterial overgrowth (SIBO). All subjects completed baseline and on-treatment evaluation of colonic transit by scintigraphy, mucosal permeability by lactulose-mannitol excretion, and fecal microbiome, bile acids, and short chain fatty acids measured on random stool sample. Overall comparison of primary response measures between treatment groups was assessed using intention-to-treat analysis of covariance (ANCOVA, with baseline value as covariate). RESULTS: There were no significant effects of treatment on bowel symptoms, small bowel or colonic permeability, or colonic transit at 24 h. Rifaximin was associated with acceleration of ascending colon emptying (14.9±2.6 h placebo; 6.9±0.9 h rifaximin; P=0.033) and overall colonic transit at 48 h (geometric center 4.0±0.3 h placebo; 4.7±0.2 h rifaximin; P=0.046); however, rifaximin did not significantly alter total fecal bile acids per g of stool or proportion of individual bile acids or acetate, propionate, or butyrate in stool. Microbiome studies showed strong associations within subjects, modest associations with time across subjects, and a small but significant association of microbial richness with treatment arm (rifaximin vs. treatment). CONCLUSIONS: In nonconstipated IBS without documented SIBO, rifaximin treatment is associated with acceleration of colonic transit and changes in microbial richness; the mechanism for reported symptomatic benefit requires further investigation.

Analytical and clinical validation of an LC-MS/MS method for urine leukotriene E4: A marker of systemic mastocytosis.

OBJECTIVES: Systemic mastocytosis (SM) is a disorder characterized by the excessive accumulation of clonally derived mast cells in various tissues. When triggered, mast cells release large amounts of histamine, prostaglandins and leukotrienes. Leukotriene E4 (LTE4) is the primary stable metabolite of total cysteinyl leukotrienes. We hypothesized that secretion of LTE4 would be increased in SM and could be used alone or in combination with current urinary biomarkers to optimize screening for SM. DESIGN AND METHODS: LTE4 was measured by liquid chromatography followed by tandem mass spectrometry (LC-MS/MS). Analytical assay validation was performed using residual urine specimens. LTE4 results were normalized to urine creatinine for clinical use. Reference interval was established using a healthy volunteer cohort. Clinical sensitivity and specificity for SM detection were determined by measuring urinary biomarkers (LTE4, N-methyl histamine [NMH] and 11ß-prostaglandin F2α [BPG]) in a cohort of 409 patients referred to allergy specialists, 66 (16%) of which were diagnosed with SM. RESULTS: Urinary LTE4 measurement was accurate, precise and linear across a range of 31-3020pg/mL. The 95th percentile of the reference interval population was <104pg/mg creatinine. Median urine LTE4 concentrations were significantly higher among patients with SM (97pg/mg cr. vs. 50pg/mg cr.; p<0.01). Elevated urinary LTE4 was 48% sensitive and 84% specific for SM. Clinical sensitivity was 53% for BPG (>1000ng/mL) and 71% for NMH (>200ng/mL). Incorporating all three urinary metabolites improved the SM diagnostic sensitivity to 97%, with minimal change in specificity. CONCLUSIONS: We have developed a sensitive and precise LC-MS/MS assay for quantitation of LTE4 in urine. Incorporating LTE4 into a panel including BPG and NMH provides a much-needed screening tool for a complicated disease with non-specific symptoms and invasive confirmatory testing.

Validation of a proposed novel equation for estimating LDL cholesterol.

BACKGROUND: Aggressive LDL cholesterol (LDL-C)-lowering strategies are recommended for primary and secondary prevention of cardiovascular events. A newly derived equation for LDL-C estimation was recently published that addressed limitations in the commonly used Friedewald LDL-C calculation method. The novel method was reported to classify patients with superior concordance to measured LDL-C compared to the Friedewald method, particularly in patients with LDL-C <70 mg/dL. METHODS: We evaluated the performance of the novel method within an independent cohort of 23 055 patients with LDL-C measured by the gold standard ß-quantification reference method. RESULTS: Overall Friedewald underestimated and the novel method overestimated measured LDL-C. Both estimations significantly deviated from the reference method when LDL-C was <70 mg/dL. Overall, the Friedewald and novel calculations correctly classified 77% and 78% of patients, respectively. The largest discrepancy in classification was observed in individuals with measured LDL-C <70 mg/dL. For this group the novel calculation would reclassify 8.7% of patients as >70 mg/dL compared to the Friedewald equation. CONCLUSIONS: We compared both novel and Friedewald estimated LDL-C against the LDL-C reference method; in contrast, the prior study relied on validation of a subset of samples by ß-quantification to allow the use of the vertical autoprofile method for LDL-C measurement. We conclude that the novel method has some benefits but it is unclear whether improvements over the Friedewald calculation are substantive enough to justify making the change in routine clinical practice and to improve patient outcomes.