Canadian society of clinical chemists (CSCC) interim consensus guidance for testing and reporting of SARS-CoV-2 serology.

Clinical laboratories across the world are working to validate and perform testing for SARS-CoV-2 antibodies. Herein, we present interim consensus guidance for Canadian clinical laboratories testing and reporting SARS-CoV-2 serology, with emphasis on the capabilities and limitations of these tests and recommendations for interpretative comments in an effort to achieve harmonized laboratory practices. The consensus document provides a broad overview of topics including sample type and contamination risk; kinetics of antibody response to COVID-19 and the impact on serology testing; clinical utility of SARS-CoV-2 serology testing; clinical performance of commercial laboratory-based assays commonly deployed in North America; recommendations for interim reporting; utility of SARS-CoV-2 antibody testing for pediatric patients; and utility of point-of-care testing. The information is based on the current literature and is subject to change as additional information becomes available.

Comparison of Glycated Hemoglobin Results Based on At-Home and In-Lab Dried Blood Spot Sampling to Routine Venous Blood Sampling In-Lab in Adult Patients With Type 1 or Type 2 Diabetes.

OBJECTIVES: Regular measurement of glycated hemoglobin (A1C) is logistically demanding. Home blotter-paper collection offers an alternative. This study tested the viability of at-home blotter-paper A1C measurement. METHODS: Objective: compare accuracy of A1C levels collected on blotter paper at home (home-blotter) and blotter-paper collection in laboratory (lab-blotter) with venous A1C (routine measurement). Agreement was assessed by Pearson correlation, Lin concordance correlation coefficient (CCC), positive and negative predictive values (PPVs, NPVs) and Bland-Altman plots and associated statistics. RESULTS: Home-blotter, lab-blotter and venous A1C correlated strongly (0.93, 0.93). Home- and lab-blotter results were upwardly biased (0.387%, 0.1%). Bias increased with time. Bias correction provided agreement for both blotters (CCC >0.9); blotters correctly identifying levels above 7% (53 mmol/mol) were 100% for corrected home-blotters and 87% (95% confidence interval) for corrected lab-blotters. NPVs (% blotters correctly identifying levels of 7% or lower [53 mmol/mol]) were 100% for corrected home-blotters and 83% for corrected lab-blotters. After correction, >92% of corrected blotters had errors of 8% or less. Of our subjects, 88.5% found home sampling preferable to routine laboratory sampling. CONCLUSIONS: Home-blotter collection is an alternative to routine collection.

Effect of domperidone on the composition of preterm human breast milk.

OBJECTIVE: Domperidone is increasingly prescribed to improve breast milk volume despite a lack of evidence regarding its effects on breast milk composition. We examined the effect of domperidone on the nutrient composition of breast milk. PATIENTS AND METHODS: Forty-six mothers who had delivered infants at <31 weeks' gestation, who experienced lactation failure, were randomly assigned to receive domperidone or placebo for 14 days. Protein, energy, fat, carbohydrate, sodium, calcium, and phosphate levels in breast milk were measured on days 0, 4, 7, and 14, serum prolactin levels were measured on days 0, 4, and 14, and total milk volume was recorded daily. Mean within-subject changes in nutrients and milk volumes were examined. RESULTS: Maternal and infant characteristics, serum prolactin level, and breast milk volume and composition were not significantly different between domperidone and placebo groups on day 0. By day 14, breast milk volumes increased by 267% in the domperidone-treated group and by 18.5% in the placebo group (P = .005). Serum prolactin increased by 97% in the domperidone group and by 17% in the placebo group (P = .07). Mean breast milk protein declined by 9.6% in the domperidone group and increased by 3.6% in the placebo group (P = .16). Changes in energy, fat, carbohydrate, sodium, and phosphate content were also not significantly different between groups. Significant increases were observed in breast milk carbohydrate (2.7% vs -2.7%; P = .05) and calcium (61.8% vs -4.4%; P = .001) in the domperidone versus placebo groups. No significant adverse events were observed among mothers or infants. CONCLUSION: Domperidone increases the volume of breast milk of preterm mothers experiencing lactation failure, without substantially altering the nutrient composition.

Bone turnover markers in the management of postmenopausal osteoporosis.

Osteoporosis is the most common cause of fragility fractures. Bone remodelling is essential for repairing damaged areas within bone to preserve bone strength and for assisting in mineral homeostases. In young adults, bone remodelling is usually balanced with approximately as much bone replaced as is removed during each remodelling cycle. However, when remodelling becomes accelerated in combination with an imbalance that favours bone resorption over formation, such as during menopause, precipitous losses in bone mass occur. Bone turnover markers (BTMs) measure the rate of bone remodelling allowing for a dynamic assessment of skeletal status and hold promise in identifying those at highest risk of rapid bone loss and subsequent fracture. Further, the use of BTMs to monitor individuals administered osteoporosis therapy is attractive as monitoring anti-fracture efficacy with bone mineral density has significant limitations. This review details remodelling biology, pre-analytical and analytical sources of variability for BTMs, describes the most commonly used resorption and formation markers, and offers some guidelines for their use and interpretation in the laboratory and the clinic.

Effect of homocysteine concentration in early pregnancy on gestational hypertensive disorders and other pregnancy outcomes.

BACKGROUND: Increased total homocysteine (tHcy) may be associated with placental-mediated adverse pregnancy outcomes, but few prospective studies have measured tHcy before pregnancy outcome. This study was undertaken to determine whether increased tHcy measured in early pregnancy is associated with pregnancy loss, gestational hypertension (GH), preeclampsia, or small for gestational age (SGA) infants. METHODS: We conducted a prospective cohort study between 2002 and 2005. We measured tHcy and serum folate in blood samples from pregnant women (<20 weeks' gestation) and collected detailed pregnancy information through a questionnaire and medical record review. RESULTS: Of the 2119 women included in the study, 103 had a pregnancy loss, 115 had gestational hypertension, 65 had preeclampsia, and 129 had an SGA infant. Subjects with increased tHcy concentrations were at increased risk of pregnancy loss [relative risk (RR) 2.1, 95% CI 1.2-3.6] or preeclampsia (RR 2.7, 95% CI 1.4-5.0) than subjects with lower tHcy concentrations, but increased tHcy concentration was not associated with increased risk of developing GH or having an SGA infant. CONCLUSION: The finding of high tHcy in early pregnancy as a risk factor for pregnancy loss and preeclampsia is consistent with a hypothesis that increased tHcy results in abnormalities of the placental vasculature.

Study protocol: a double blind placebo controlled trial examining the effect of domperidone on the composition of breast milk [NCT00308334].

BACKGROUND: Domperidone, a drug that enhances upper gastric motility, is an anti-dopaminergic medication that also elevates prolactin levels. It has been shown to safely increase the milk supply of lactating women. To date, researchers have analyzed the effects of domperidone on lactating woman with respect to the quantity of their milk production, adverse effects, and drug levels in the breast milk. However, the effect of domperidone on the macronutrient composition of breast milk has not been studied and current guidelines for fortification of human milk for premature infants do not distinguish between those women using or those not using domperidone. The purpose of this study is to evaluate the effect of domperidone (given to lactating mothers of very preterm infants) on the macronutrient composition of breast milk. METHODS/DESIGN: Mothers of infants delivered at less than 31 weeks gestation, who are at least 3 weeks postpartum, and experiencing lactational failure despite non-pharmacological interventions, will be randomized to receive domperidone (10 mg three times daily) or placebo for a 14-day period. Breast milk samples will be obtained the day prior to beginning treatment and on days 4, 7 and 14. The macronutrient (protein, fat, carbohydrate and energy) and macromineral content (calcium, phosphorus and sodium) will be analyzed and compared between the two groups. Additional outcome measures will include milk volumes, serum prolactin levels (measured on days 0, 4, and 10), daily infant weights and breastfeeding rates at 2 weeks post study completion and at discharge. Forty-four participants will be recruited into the study. Analysis will be carried out using the intention to treat approach. DISCUSSION: If domperidone causes significant changes to the nutrient content of breast milk, an alteration in feeding practices for preterm infants may need to be made in order to optimize growth, nutrition and neurodevelopment outcomes.

Things we have learned from tilapia islet xenotransplantation.

An islet xenotransplantation model has been developed using tilapia (Oreochromis niloticus) as the donors. Studies using this model for the treatment of experimental type 1 diabetes in mice have produced promising results including the maintenance of long-term normoglycemia and mammalian-like glucose tolerance profiles in islet graft recipients. Islet encapsulation has also provided a promising method for the prevention of graft rejection, and strains of transgenic tilapia expressing a [desThrB30] human insulin molecule have been produced. In addition to studying islet transplantation for the treatment of type 1 diabetes, these studies have also produced insights into piscine glucose homeostasis. Studies demonstrating the glucose responsiveness of tilapia islets are described. In addition, work performed by our group and by others pertaining to presence and nature of piscine glucose transporters is reviewed. Finally, studies addressing some of the broader challenges of islet xenotransplantation are discussed with particular attention paid to the post-transplantation fate of the various islet cell populations and the proteins they produce.

Tandem mass spectrometry in the clinical chemistry laboratory.

Tandem mass spectrometry is becoming an increasingly important analytical technology in the clinical laboratory environment. Applications in toxicology and therapeutic drug monitoring have opened the door for tandem mass spectrometry and now we are seeing a vast array of new applications being developed. It has been the combination of tandem mass spectrometry with sample introduction techniques employing atmospheric pressure ionization that has enabled this technology to be readily implemented in the clinical laboratory. Although its major research applications started with pharmacology and proteomics, tandem mass spectrometry is being used for a great variety of analyses from steroids to catecholamines to peptides. As with chromatographic methods, tandem mass spectrometry is most cost effective when groups of compounds need to be measured simultaneously. However as the price/performance of this technology continues to improve, it will become even more widely utilized for clinical laboratory applications.