A Snapshot of Lipid-Reporting Practices in Canadian Clinical Laboratories: An Urgent Need for Harmonisation.

To effectively implement the Canadian Cardiovascular Society (CCS) guidelines for dyslipidemia management into clinical laboratories, clear recommendations for lipid reporting are essential. In this study, the Canadian Society of Clinical Chemists Working Group on Reference Interval Harmonisation surveyed Canadian laboratories on adult lipid reporting practices to set a foundation for the development and implementation of harmonised lipid reporting across Canada. Key aspects of the survey asked laboratories: what reporting parameters were in place to assess lipid results; what interpretative comments were provided; whether nonfasting lipids were permitted and, if so, what strategy was used to document fasting status; and whether there was interest in implementing a harmonised lipid report. A total of 101 laboratories were represented by 24 respondents, as many responses were submitted by laboratory networks that included more than 1 laboratory. There was at least 1 response from 9 Canadian provinces and representation across 5 testing platforms. Upper and lower limits for lipid parameters and referenced source of limits varied substantially across laboratories, with only 56% of laboratories (9 respondents) referencing the 2016 CCS guidelines. Eighty-six percent of laboratories (19 respondents) report nonfasting lipids, although the method of documenting nonfasting status varied. Overall, 36% of laboratories (8 respondents) reported interest in implementing a harmonised lipid report. Assessment of current lipid-reporting practices supports the need for harmonised lipid reporting across Canada. Development of a harmonised lipid report for the adult population, consistent with up-to-date Canadian guidelines, will improve continuity of lipid test interpretation across Canada and improve clinical decision making.

Operational considerations and challenges of biochemistry laboratories during the COVID-19 outbreak: an IFCC global survey.

Objectives: The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on COVID-19 conducted a global survey to understand how biochemistry laboratories manage the operational challenges during the coronavirus disease 2019 (COVID-19) pandemic. Materials and methods: An electronic survey was distributed globally to record the operational considerations to mitigate biosafety risks in the laboratory. Additionally, the laboratories were asked to indicate the operational challenges they faced. Results: A total of 1210 valid submissions were included in this analysis. Most of the survey participants worked in hospital laboratories. Around 15% of laboratories restricted certain tests on patients with clinically suspected or confirmed COVID-19 over biosafety concerns. Just over 10% of the laboratories had to restrict their test menu or services due to resource constraints. Approximately a third of laboratories performed temperature monitoring, while two thirds of laboratories increased the frequency of disinfection. Just less than 50% of the laboratories split their teams. The greatest reported challenge faced by laboratories during the COVID-19 pandemic is securing sufficient supplies of personal protective equipment (PPE), analytical equipment, including those used at the point of care, as well as reagents, consumables and other laboratory materials. This was followed by having inadequate staff, managing their morale, anxiety and deployment. Conclusions: The restriction of tests and services may have undesirable clinical consequences as clinicians are deprived of important information to deliver appropriate care to their patients. Staff rostering and biosafety concerns require longer-term solutions as they are crucial for the continued operation of the laboratory during what may well be a prolonged pandemic.

Laboratory practices to mitigate biohazard risks during the COVID-19 outbreak: an IFCC global survey.

Objectives: A global survey was conducted by the IFCC Task Force on COVID-19 to better understand how general biochemistry laboratories manage the pre-analytical, analytical and post-analytical processes to mitigate biohazard risks during the coronavirus disease 2019 (COVID-19) pandemic. Methods: An electronic survey was developed to record the general characteristics of the laboratory, as well as the pre-analytical, analytical, post-analytical and operational practices of biochemistry laboratories that are managing clinical samples of patients with COVID-19. Results: A total of 1210 submissions were included in the analysis. The majority of responses came from hospital central/core laboratories that serve hospital patient groups and handle moderate daily sample volumes. There has been a decrease in the use of pneumatic tube transport, increase in hand delivery and increase in number of layers of plastic bags for samples of patients with clinically suspected or confirmed COVID-19. Surgical face masks and gloves are the most commonly used personal protective equipment (PPE). Just >50% of the laboratories did not perform an additional decontamination step on the instrument after analysis of samples from patients with clinically suspected or confirmed COVID-19. A fifth of laboratories disallowed add-on testing on these samples. Less than a quarter of laboratories autoclaved their samples prior to disposal. Conclusions: The survey responses showed wide variation in pre-analytical, analytical and post-analytical practices in terms of PPE adoption and biosafety processes. It is likely that many of the suboptimal biosafety practices are related to practical local factors, such as limited PPE availability and lack of automated instrumentation.

Postprandial Dyslipidemia: Pathophysiology and Cardiovascular Disease Risk Assessment.

Although the fed state predominates over the course of a day, the fasting lipid profile has traditionally been used to assess cardiovascular disease (CVD) risk. The nonfasting lipid profile may be more reflective of the daily circulating plasma lipids and simplifies lipid monitoring for patients, laboratories, and clinicians. Nonfasting triglyceride levels are also independently associated with cardiovascular events, leading to several clinical guidelines (e.g. in Denmark, the UK, Europe, and Canada) now recommending nonfasting lipid testing in the primary prevention setting. Obese and insulin resistant states are associated with intestinal chylomicron overproduction and subsequent remnant lipoprotein accumulation, leading to development of postprandial dyslipidemia in the fed state. Postprandial dyslipidemia is thought to be a major contributor of atherogenesis and shown to be an important CVD risk factor. As intestinal peptides (e.g. glucagon-like-peptide 1; GLP-1) have been shown to regulate chylomicron output, alterations in these signaling pathways in insulin resistant states may play a role in the development and/or progression of postprandial dyslipidemia. Although several advances have been made in understanding postprandial dyslipidemia in insulin resistance and its association with CVD, several limitations remain. Although nonfasting lipid measurements (i.e. random blood sampling) are now recommended in some countries, a more functional assessment of postprandial lipemia involves ingestion of a high-fat meal with subsequent blood collection over a specified time period (i.e. oral fat tolerance test). However, oral fat tolerance test methodology remains largely unstandardized and reference values to interpret postprandial values remain to be accurately established. Development of standardized methodologies and biomarker profiles for assessment of postprandial dyslipidemia in clinical practice will enable early and accurate identification of those at risk for CVD.

Pediatric Metabolic Syndrome: Pathophysiology and Laboratory Assessment.

Pediatric overweight and obesity is an emerging public health priority as rates have rapidly increased worldwide. Obesity is often clustered with other metabolic abnormalities including hypertension, dyslipidemia, and insulin resistance, leading to increased risk of cardiovascular disease. This cluster of risk factors, termed the metabolic syndrome, has traditionally been reported in adults. However, with the increased prevalence of pediatric obesity, the metabolic syndrome is now evident in children and adolescents. This complex cluster of risk factors is the result of the pathological interplay between several organs including adipose tissue, muscle, liver, and intestine with a common antecedent - insulin resistance. The association of the metabolic syndrome with several systemic alterations that involve numerous organs and tissues adds to the complexity and challenge of diagnosing the metabolic syndrome and identifying useful clinical indicators of the disease. The complex physiology of growing and developing children and adolescents further adds to the difficulties in standardizing laboratory assessment, diagnosis, and prognosis for the diverse pediatric population. However, establishing a consensus definition is critical to identifying and managing children and adolescents at high risk of developing the metabolic syndrome. As a result, the examination of novel metabolic syndrome biomarkers which can detect these metabolic abnormalities early with high specificity and sensitivity in the pediatric population has been of interest. Understanding this complex cluster of risk factors in the pediatric population is critical to ensure that this is not the first generation where children have a shorter life expectancy than their parents. This review will discuss the pathophysiology, consensus definitions and laboratory assessment of pediatric metabolic syndrome as well as potential novel biomarkers.

Laboratory reference intervals in the assessment of iron status in young children.

OBJECTIVES: The primary objective was to establish reference intervals for laboratory tests used to assess iron status in young children using the Clinical and Laboratory Standards Institute guidelines. A secondary objective was to compare the lower limit of the reference interval with the currently recommended cut-off value for haemoglobin and serum ferritin in children 1-3 years of age. METHODS: Blood samples were obtained from healthy children recruited during scheduled health supervision visits with their primary care physician. For our primary objective, outliers were removed; age partitions were selected and analysis of variance and pairwise comparisons were made between adjacent partitions; reference intervals and 90% CIs were calculated. For our secondary objective, we determined the proportion of children misclassified using the lower limit reference interval compared with the cut-off value. RESULTS: Samples from 2305 male and 2029 female participants (10 days to 10.6 years) were used to calculate age and sex-specific reference intervals for laboratory tests of iron status. There were statistically significant differences between adjacent age partitions for most analytes. Approximately 10% of children 1-3 years of age were misclassified (underestimated) using the lower limit of the reference intervals rather than the currently recommended cut-off values for haemoglobin and serum ferritin. IMPLICATIONS AND RELEVANCE: Clinical laboratories may consider adopting published paediatric reference intervals. Reference intervals may misclassify (underestimate) children with iron deficiency as compared with currently recommended cut-off values. Future research on decision limits derived from clinical studies of outcomes is a priority.

CLSI-based transference of the CALIPER database of pediatric reference intervals from Abbott to Beckman, Ortho, Roche and Siemens Clinical Chemistry Assays: direct validation using reference samples from the CALIPER cohort.

OBJECTIVES: The CALIPER program recently established a comprehensive database of age- and sex-stratified pediatric reference intervals for 40 biochemical markers. However, this database was only directly applicable for Abbott ARCHITECT assays. We therefore sought to expand the scope of this database to biochemical assays from other major manufacturers, allowing for a much wider application of the CALIPER database. DESIGN AND METHODS: Based on CLSI C28-A3 and EP9-A2 guidelines, CALIPER reference intervals were transferred (using specific statistical criteria) to assays performed on four other commonly used clinical chemistry platforms including Beckman Coulter DxC800, Ortho Vitros 5600, Roche Cobas 6000, and Siemens Vista 1500. The resulting reference intervals were subjected to a thorough validation using 100 reference specimens (healthy community children and adolescents) from the CALIPER bio-bank, and all testing centers participated in an external quality assessment (EQA) evaluation. RESULTS: In general, the transferred pediatric reference intervals were similar to those established in our previous study. However, assay-specific differences in reference limits were observed for many analytes, and in some instances were considerable. The results of the EQA evaluation generally mimicked the similarities and differences in reference limits among the five manufacturers' assays. In addition, the majority of transferred reference intervals were validated through the analysis of CALIPER reference samples. CONCLUSIONS: This study greatly extends the utility of the CALIPER reference interval database which is now directly applicable for assays performed on five major analytical platforms in clinical use, and should permit the worldwide application of CALIPER pediatric reference intervals.

Toxicological assessment of industrial solvents using human cell bioassays: assessment of short-term cytotoxicity and long-term genotoxicity potential.

There is an increasing demand for simple toxicological screening methods to assess the human health risk associated with exposure to environmental toxicants. Such screening tools should allow for risk evaluation in terms of both short-term/acute toxicity and longer-term genetic damage, which may lead to mutagenicity and carcinogenicity. We employed a battery of human cell bioassays using the human hepatoma cell-line, HepG2, to assess the cytotoxic and genotoxic potential of environmental pollutants. Here, we demonstrate direct application of these human cell bioassays to the toxicological assessment of a number of industrial solvents that are in common use worldwide. HepG2 cells were exposed to various solvents at concentrations ranging from 25 to 500 ppm. The cells were then analysed using specific protocols for four different adverse effects: cell death/acute cytotoxicity using a neutral red uptake assay, altered enzyme function (often an indicator of cell stress) using the ethoxyresorufin O-deethylase (EROD) bioassay, DNA single strand breaks (SSB), and DNA repair induction, which evaluates mutagenic activity. Using the positive controls, linear dose-response curves were achieved for all four bioassays. The high sensitivity of the tests allowed for environmentally meaningful assessments, and precision studies showed excellent reproducibility for all four bioassays. Comparing the results of the four bioassays on each of 16 industrial solvents allowed for ranking of the anticipated relative human toxicity of these solvents, which were comparable with data from standard toxicity tests and human occupational data. Overall, the study clearly supports the application of the HepG2 cell bioassay system for rapid toxicological screening of many candidate toxicants for both short- and long-term toxicity potential.

The relationship between homeostasis model assessment and cardiovascular risk factors in Iranian subjects with normal fasting glucose and normal glucose tolerance.

BACKGROUND: Insulin resistance is a complex problem which may not always correlate with all its cardiovascular risk factors in various populations. We investigated the relationship between homeostasis model assessment of insulin resistance (HOMA-IR) with cardiovascular risk factors in Iranian subjects with normal fasting glucose (NFG) and normal glucose tolerance (NGT). METHODS: Of the 605 subjects aged 25-79 y enrolled in this study, after the oral glucose tolerance test, 366 subjects aged 25-50 y and 135 aged >50 y were classified as NFG and NGT. Insulin resistance was estimated by the HOMA-IR. RESULTS: Women had higher values of body mass index (BMI), insulin and HOMA-IR than men in both age groups. The prevalence of insulin resistance, general and abdominal obesity, low HDL-C and physical inactivity was higher in women than men in the 2 age groups. Men had a higher prevalence of hypertension and hypertriglyceridemia in the group with age 25-50 y. The Pearson correlation controlled for age, BMI, waist circumference and physical activity showed that HOMA-IR had significant correlation with triglyceride and inversely associated with HDL-C in both sexes. In addition, the results of HOMA-IR quartiles demonstrated that the prevalence of hypertension, obesity, and low HDL-C was particular high in women with HOMA-IR >2.39. Multiple regression indicated that log HOMA-IR was independently predicted by BMI, triglyceride and HDL-C in men and BMI, HDL-C and waist-to-hip (WHR) ratio in women. CONCLUSIONS: HOMA-IR is associated with the features of metabolic syndrome with a sex difference in the degree and predictors of HOMA-IR and the frequency of cardiovascular risk factors.