A multicenter analytical performance evaluation of a multiplexed immunoarray for the simultaneous measurement of biomarkers of micronutrient deficiency, inflammation and malarial antigenemia.

A lack of comparative data across laboratories is often a barrier to the uptake and adoption of new technologies. Furthermore, data generated by different immunoassay methods may be incomparable due to a lack of harmonization. In this multicenter study, we describe validation experiments conducted in a single lab and cross-lab comparisons of assay results to assess the performance characteristics of the Q-plex™ 7-plex Human Micronutrient Array (7-plex), an immunoassay that simultaneously quantifies seven biomarkers associated with micronutrient (MN) deficiencies, inflammation and malarial antigenemia using plasma or serum; alpha-1-acid glycoprotein, C-reactive protein, ferritin, histidine-rich protein 2, retinol binding protein 4, soluble transferrin receptor, and thyroglobulin. Validations included repeated testing (n = 20 separately prepared experiments on 10 assay plates) in a single lab to assess precision and linearity. Seven independent laboratories tested 76 identical heparin plasma samples collected from a cohort of pregnant women in Niger using the same 7-plex assay to assess differences in results across laboratories. In the analytical validation experiments, intra- and inter-assay coefficients of variation were acceptable at <6% and <15% respectively and assay linearity was 96% to 99% with the exception of ferritin, which had marginal performance in some tests. Cross-laboratory comparisons showed generally good agreement between laboratories in all analyte results for the panel of 76 plasma specimens, with Lin's concordance correlation coefficient values averaging ≥0.8 for all analytes. Excluding plates that would fail routine quality control (QC) standards, the inter-assay variation was acceptable for all analytes except sTfR, which had an average inter-assay coefficient of variation of ≥20%. This initial cross-laboratory study demonstrates that the 7-plex test protocol can be implemented by users with some experience in immunoassay methods, but familiarity with the multiplexed protocol was not essential.

Vincristine-induced peripheral neurotoxicity: A prospective cohort.

Vincristine-induced peripheral neuropathy (VIPN) is a serious and pervasive problem, affecting 12-78% of pediatric patients, based on retrospective studies. The study objective was to prospectively collect a cohort of well-phenotyped patients receiving vincristine in order to accurately classify and grade their neurotoxicity. All children in British Columbia with leukemia or lymphoma requiring vincristine between 2013 and 2016 were approached for consent. Those recruited were assessed by occupational and physiotherapists at baseline, mid and endpoint of their treatment. Assessments included the Bruininks-Oseretsky Test of Motor Proficiency - 2nd ed. (BOT-2), strength, "Timed up and go" test and vibration sensibility. Seventy-two patients consented (age: 2.0-18.7 years). The majority were below average for age on one or more BOT-2 domains at midpoint (N = 32/45, 71%), which decreased by the endpoint (N = 19/41, 46%, p = .049). Six patients showed severe VIPN throughout treatment (N = 6/53, 11%), defined as a BOT-2 score well below average. Muscle strength for wrist extension/flexion, anterior tibialis and peronei decreased significantly between baseline (Median = 5) and midpoint (Median = 4), with no significant change noted by endpoint. Most patients had normal vibration sensibility in lower (N = 30/60, 50%) and upper limbs (N = 26/38, 68%). In conclusion, with no differences between time points. VIPN is highly prevalent among patients with pediatric cancer, causing significant morbidity and functional deficits. Identification of risk factors would allow for resource appropriation to patients at higher risk, as well as potentially permitting dose escalation in patients with low toxicity to improve survival.

Menstrual blood losses and body mass index are associated with serum ferritin concentrations among female varsity athletes.

Preventing and treating iron deficiency are important components in the nutritional care of female varsity athletes, as these interventions may improve aerobic endurance and athletic performance. We examined the factors associated with ferritin concentration in 30 female varsity athletes (18-30 years) at the University of British Columbia in Vancouver, Canada. Biochemical indicators of iron and inflammation status, dietary intake, supplementation practices, weight, height, and menstrual blood losses were assessed. Iron deficiency prevalence was 20% (n = 6/30; inflammation-adjusted ferritin <15 µg/L). Multiple linear regression was used to assess the associations of a number of independent explanatory variables with log-transformed serum ferritin (µg/L) as the continuous outcome variable. A 1-unit increase in body mass index (BMI; kg/m2) was associated with 22% (95% CI: 9%-37%) higher mean ferritin concentrations, and a 1-point increase in menstrual loss score was associated with 1% (95% CI: 1%-2%) lower ferritin concentrations. Hemoglobin and hepcidin concentrations, inflammation biomarkers, consumption of iron supplements in any form or dose for ≥3 days/week, and age were not significantly associated with ferritin concentrations in the final adjusted model. Novelty Estimated monthly menstrual losses and BMI were associated with serum ferritin concentrations in female athletes in our study. These are easy-to-measure, noninvasive measurements that should be considered in the assessment of risk of iron deficiency in female athletes.

Diet and cardiometabolic side effects in children treated with second-generation antipsychotics.

BACKGROUND: Second-generation antipsychotic (SGA) treatment in children is associated with metabolic side effects including weight gain, dyslipidemia, and insulin resistance. The objective of this study is to determine if SGA treatment in children affects dietary intakes and relationship to metabolic side effects. METHODS: Three-day food records assessed dietary energy and macronutrient intakes in a cross-sectional population of SGA-treated (n = 35) and SGA-naïve (n = 29) children. RESULTS: SGA-treated children had more overweight/obesity (BMI ≥ 85th percentile for age and sex, p = 0.001); waist circumference (WC) ≥ 90th percentile for age and sex (p = 0.007); waist:height ratio (WHtR) ≥ 85th percentile for age and sex (p = 0.004), greater HOMA-IR, (p = 0.001) and plasma triglycerides (p = 0.017), and lower plasma HDL (p = 0.029). Dietary energy intakes were not different between SGA-naïve and SGA-treated children [1734 ± 486 vs 1971 ± 649 (-135, 408) kcal/day, mean ± SD (95% CI)] after adjustments for sex, age, Tanner stage, psychostimulant use, and height. Similarly, no differences in macronutrient intakes were observed. In models adjusted for SGA treatment and physical activity, no relationships between dietary intakes and BMI were found, but dietary total energy intakes were positively associated with waist circumference z-scores (p = 0.019), systolic blood pressure z-scores (p = 0.028, also adjusted for BMI) and HOMA-IR (p = 0.013, also adjusted for age, sex, BMI). All of the children had poor diets with 87.5% having >7% of daily energy from saturated fat; 62.5% having >20% of daily energy from sugar; and almost 60% having sodium intakes above the tolerable upper intake level. CONCLUSIONS: SGA treatment is not associated with greater dietary energy intakes in children. However, dietary energy intakes are associated with greater waist circumference and systolic blood pressure z-scores and HOMA-IR in children with mental health conditions.

Serum Soluble Transferrin Receptor Concentrations Are Elevated in Congolese Children with Glucose-6-Phosphate Dehydrogenase Variants, but Not Sickle Cell Variants or α-Thalassemia.

Background: Anemia is common in Congolese children, and inherited blood disorders may be a contributing cause. The presence of sickle cell variants, X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency and α-thalassemia, has been previously reported. G6PD A- deficiency is characterized by the co-inheritance of G6PD 376 and 202 variants and is common in sub-Saharan Africa.Objective: We aimed to measure the associations between inherited blood disorders and hemoglobin, ferritin, and soluble transferrin receptor (sTfR) concentrations in Congolese children.Methods: Venous blood was collected from 744 children aged 6-59 mo from 2 provinces. We measured biomarkers of nutritional and inflammation status and malaria. Pyrosequencing was used to detect sickle cell variants. Polymerase chain reaction was used to detect G6PD variants and α-thalassemia deletions.Results: Overall, 11% of children had a sickle cell variant, 19% of boys were G6PD A- hemizygotes, 12% and 10% of girls were G6PD A- hetero- or homozygotes, respectively, and 12% of children had α-thalassemia. Multivariable linear regression models (adjusted for age, province, altitude, malaria, and biomarkers of nutritional and inflammation status) showed that G6PD A- hemizygous boys and G6PD 376 homozygous girls had higher sTfR concentrations [geometric mean ratios (95% CIs): 1.20 (1.03, 1.39) and 1.25 (1.02, 1.53), respectively] than children with no G6PD variants. Hemoglobin and ferritin concentrations were not independently associated with any of the inherited blood disorder genotypes.Conclusions: We found that 2 G6PD variant genotypes were associated with elevated sTfR concentrations, which limits the accuracy of sTfR as a biomarker of iron status in this population.

The effect of oral iron with or without multiple micronutrients on hemoglobin concentration and hemoglobin response among nonpregnant Cambodian women of reproductive age: a 2 x 2 factorial, double-blind, randomized controlled supplementation trial.

Background: Despite a high prevalence of anemia among nonpregnant Cambodian women, current reports suggest that iron deficiency (ID) prevalence is low. If true, iron supplementation will not be an effective anemia reduction strategy.Objective: We measured the effect of daily oral iron with or without multiple micronutrients (MMNs) on hemoglobin concentration in nonpregnant Cambodian women screened as anemic.Design: In this 2 × 2 factorial, double-blind, randomized trial, nonpregnant women (aged 18-45 y) with hemoglobin concentrations ≤117 g/L (capillary blood) were recruited from 26 villages in Kampong Chhnang province and randomly assigned to receive 12 wk of iron (60 mg; Fe group), MMNs (14 other micronutrients; MMN group), iron plus MMNs (Fe+MMN group), or placebo capsules. A 2 × 2 factorial intention-to-treat analysis with the use of a generalized mixed-effects model was used to assess the effects of iron and MMNs and the interaction between these factors. Results: In July 2015, 809 women were recruited and 760 (94%) completed the trial. Baseline anemia prevalence was 58% (venous blood). Mean (95% CI) hemoglobin concentrations at 12 wk in the Fe, MMN, Fe+MMN, and placebo groups were 121 (120, 121), 116 (116, 117), 123 (122, 123), and 116 (116, 117) g/L, with no iron × MMN interaction (P = 0.66). Mean (95% CI) increases in hemoglobin were 5.6 g/L (3.8, 7.4 g/L) (P < 0.001) among women who received iron (n = 407) and 1.2 g/L (-0.6, 3.0 g/L) (P = 0.18) among women who received MMNs (n = 407). The predicted proportions (95% CIs) of women with a hemoglobin response (≥10 g/L at 12 wk) were 19% (14%, 24%), 9% (5%, 12%), 30% (24%, 35%), and 5% (2%, 9%) in the Fe, MMN, Fe+MMN, and placebo groups, respectively.Conclusions: Daily iron supplementation for 12 wk increased hemoglobin in nonpregnant Cambodian women; however, MMNs did not confer additional significant benefit. Overall, ∼24% of women who received iron responded after 12 wk; even fewer would be likely to respond in the wider population. This trial was registered at clinicaltrials.gov as NCT02481375.