Re-evaluating the utility of iron indices in hereditary hemochromatosis genotyping: A retrospective study.

Introduction: Hereditary hemochromatosis (HH), associated with C282Y or H63D mutations in the HFE gene, is the commonest genetic disorder in Canada. The majority of HH cases are attributable to C282Y homozygosity which can precipitate iron overload and organ damage, but with low penetrance. Elevated transferrin saturation (TSat) and ferritin levels are key biochemical indicators of iron overload in C282Y homozygotes.

Canadian guidance for diagnosis and management of acute hepatic porphyrias.

Acute hepatic porphyrias (AHP) comprise four rare monogenic autosomal conditions. Each is linked to a deficiency of heme metabolizing enzymes. Common manifestations include severe abdominal pain, nausea, confusion, hyponatremia, hypertension, tachycardia, and neuropathy.

Effective stewardship strategies to enhance appropriateness of refer-out test requests in a Canadian tertiary centre laboratory.

Objectives: Specialized testing conducted in reference laboratories is costly and often not optimally directed. Since 2016, our institution has worked to ensure the appropriateness of refer-out (RO) tests. We examine the impact of utilization initiatives on the patterns of requests and completed tests.

Off-road vehicle crashes: dangers of alcohol and drug impairment.

Background: Impaired driving is a public health issue, yet little is known concerning the prevalence of substance use in drivers involved in off-road vehicle crashes. The goal of the present study was to describe the demographics and prevalence of alcohol and drug use in drivers of off-road vehicle crashes.

Methods: In this observational substudy, we collected clinical and toxicological data on all moderately or severely injured off-road vehicle drivers who had blood samples obtained within 6 h of the crash.

The analytical performance of six urine drug screens on cobas 6000 and ARCHITECT i2000 compared to LC-MS/MS gold standard.

Background: Immunoassays provide a rapid tool for the screening of drugs-of-abuse (DOA). However, results are presumptive and confirmatory testing is warranted. To reduce associated cost and delay, laboratories should employ assays with high positive and negative predictive values (PPVs and NPVs).

Multiple pre- and post-analytical lean approaches to the improvement of the laboratory turnaround time in a large core laboratory.

Background: Core laboratory (CL), as a new business model, facilitates consolidation and integration of laboratory services to enhance efficiency and reduce costs. This study evaluates the impact of total laboratory automation system (TLA), electric track vehicle (ETV) system and auto-verification (AV) of results on overall turnaround time (TAT) (phlebotomy to reporting TAT: PR-TAT) within a CL setting.

Methods: Mean, median and percentage of outlier (OP) for PR-TAT were compared for pre- and post-CL eras using five representative tests based on different request priorities.

Evaluation of the impact of a total automation system in a large core laboratory on turnaround time.

Background: Growing financial and workload pressures on laboratories coupled with user demands for faster turnaround time (TAT) has steered the implementation of total laboratory automation (TLA). The current study evaluates the impact of a complex TLA on core laboratory efficiency through the analysis of the In-lab to Report TAT (IR-TAT) for five representative tests based on the different requested priorities.

Methods: Mean, median and outlier percentages (OP) for IR-TAT were determined following TLA implementation and where possible, compared to the pre-TLA era.

An effective utilization management strategy by dual approach of influencing physician ordering and gate keeping.

Objectives: There is increasing recognition of the importance of appropriate laboratory test utilization. We investigate the effect of a multifaceted educational approach that includes physician feedback on individual test ordering, in conjunction with targeted restriction, on the utilization of selected laboratory tests.

Design And Methods: Scientific evidence was compiled on the usefulness and limitations of tests suspected of being over utilized in our laboratories.

Pushing the limits of chemistry point-of-care testing for the management of patients under investigation for Ebola virus disease.

Background: With the recent outbreak in West Africa, hospitals worldwide have been developing protocols for suspect of cases of Ebola virus disease. Patients with Ebola virus disease present with a severe gastroenteritis leading to dehydration and electrolyte abnormalities and as such, routine chemistry analysis is essential for patient management. While point-of-care testing can be used with additional precautions for rapid chemistry analyses in a laboratory setting, significant delays could ensue before specimens arrive to the laboratory.

Loss of expression of DNA mismatch repair proteins is rare in pancreatic and small intestinal neuroendocrine tumors.

Context: Two recent studies have identified a high rate of microsatellite instability (MSI) in pancreatic neuroendocrine tumors (pNETs). Microsatellite instability is rare in small intestinal neuroendocrine tumors (NETs). It is unclear why there is discordance in the frequency of MSI in the 2 studies of pNETs and why this mechanism is comparatively rare in small intestinal tumors.

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.

Apolipoprotein E-polymorphism, frailty and mortality in older adults.

Although apolipoprotein E (ApoE) polymorphism is associated with variable risks of several illnesses, and with mortality, no persuasive relationship has been demonstrated with frailty. Here, the clinical examination cohort (n=1452 older adults, aged 70+ years at baseline) of the Canadian Study of Health and Aging was evaluated, with 5-year follow-up data. Frailty was defined using both the phenotypic definition from the Cardiovascular Health Study (Frailty-CHS) and the 'Frailty Index', from which age-specific trajectories of deficit accumulation can be estimated.

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.

Folic acid improves endothelial dysfunction in type 2 diabetes--an effect independent of homocysteine-lowering.

Diabetes is associated with endothelial dysfunction, which in part may be related to uncoupling of the endothelial nitric oxide (NO) synthase enzyme, thus reducing the availability of NO. As folates may potentially reverse the uncoupling of NO synthase, we wanted to determine whether folic acid supplementation could modulate endothelial function and markers of inflammation in patients with type 2 diabetes without vascular disease. Nineteen patients with type 2 diabetes were treated with folic acid (10mg/day for 2 weeks) versus placebo in a randomized, placebo-controlled, cross-over study with an 8-week washout period between treatments.

Improved prediction of early-onset coronary artery disease using APOE epsilon4, BChE-K, PPARgamma2 Pro12 and ENOS T-786C in a polygenic model.

Objectives: Coronary artery disease (CAD) is often polygenic due to multiple mutations that contribute small effects to susceptibility. Since most prior studies only evaluated the contribution of single candidate genes, we therefore looked at a combination of genes in predicting early-onset CAD [apolipoprotein E (APOE) epsilon4, butyrylcholinesterase (BChE) K, peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala and endothelial nitric oxide synthase (ENOS) T-786C].

Design And Methods: We examined the frequencies, individually and in combination, of all four alleles among patients with early-onset CAD (n = 150; <50 years), late-onset CAD (n = 150; >65 years) and healthy controls (n = 150, age range 47-93 years).

Effect of cyclooxygenase-2 inhibition with rofecoxib on endothelial dysfunction and inflammatory markers in patients with coronary artery disease.

Objectives: The aim of this study was to determine whether selective cyclooxygenase-2 (COX-2) inhibition with rofecoxib can modulate endothelial dysfunction and levels of circulating inflammatory markers in patients with established coronary artery disease (CAD).

Background: Expression of COX-2 is upregulated in atherosclerosis. Thus, it has been hypothesized that COX-2 may contribute to atherogenesis by producing eicosanoids, which mediate vascular inflammation and endothelial dysfunction.

Microsatellite instability in multifocal urothelial carcinoma and effect on BAX and AXIN2.

Objectives: Urothelial carcinomas have a synchronous or metachronous multifocal pattern of occurrence, questioning their clonal origin. Genetic alterations such as microsatellite instability (MSI) affect various tumors including urothelial cancers. These alterations can affect repeat sequences and cause mutations in coding regions of genes involved in transformation, tumor suppression and apoptosis.

Relation between butyrylcholinesterase K variant, paraoxonase 1 (PON1) Q and R and apolipoprotein E epsilon 4 genes in early-onset coronary artery disease.

Objectives: The common K variant of butyrylcholinesterase (BChE-K), an enzyme which metabolizes acetylcholine and organophosphates, has been associated with Alzheimer's disease, especially in the presence of the apolipoprotein E epsilon 4 allele (APOE-epsilon 4). Although APOE-epsilon 4 has been associated with the development of coronary artery disease (CAD), an association between the BChE-K variant and CAD has not been explored. Paraoxonase 1 (PON1), located within HDL, is an enzyme which also metabolizes organophosphates and may be antiatherogenic.

Stability of the Bax (G)8 microsatellite in localized prostatic adenocarcinoma.

OBJECTIVES: Microsatellite instability has been found in a variety of tumors including prostate cancer. Bax, a pro-apoptotic protein from the Bcl-2 family of proteins, has a microsatellite composed of an eight deoxyguanine [(G)8] tract located in exon 3. Prostate carcinoma cells have increased proliferation indices and lower levels of apoptosis when compared to benign tissue.