Healthy Canadian Research Articles

Cardiometabolic benefits of a non-industrialized-type diet are linked to gut microbiome modulation.

Industrialization adversely affects the gut microbiome and predisposes individuals to chronic non-communicable diseases. We tested a microbiome restoration strategy comprising a diet that recapitulated key characteristics of non-industrialized dietary patterns (restore diet) and a bacterium rarely found in industrialized microbiomes (Limosilactobacillus reuteri) in a randomized controlled feeding trial in healthy Canadian adults. The restore diet, despite reducing gut microbiome diversity, enhanced the persistence of L.reuteri strain from rural Papua New Guinea (PB-W1) and redressed several microbiome features altered by industrialization. The dietalso beneficially altered microbiota-derived plasma metabolites implicated in the etiology of chronic non-communicable diseases. Considerable cardiometabolic benefits were observed independently of L.reuteri administration, several of which could be accurately predicted by baseline and diet-responsive microbiome features. The findings suggest that a dietary intervention targeted toward restoring the gut microbiome can improve host-microbiome interactions that likely underpin chronic pathologies, which can guide dietary recommendations and the development of therapeutic and nutritional strategies.

Culture collection containing 1,240 isolates from healthy Canadian laying hens.

The pure culture of prokaryotes is essential to understanding their physiology. To facilitate research into better understanding the roles of individual bacteria in the gastric microbiome in chickens, we have established a culture collection of 1,240 isolates from fecal samples collected from healthy laying hens from across Canada.

Exposure to air pollutants and subclinical carotid atherosclerosis measured by magnetic resonance imaging: A cross-sectional analysis.

Long-term exposure to air pollution has been associated with higher risk of cardiovascular mortality. Less is known about the association of air pollution with initial development of cardiovascular disease. Herein, the association between low-level exposure to air pollutants and subclinical carotid atherosclerosis in adults without known clinical cardiovascular disease was investigated. Cross-sectional analysis within a prospective cohort study. The Canadian Alliance for Healthy Hearts and Minds Cohort Study; a pan-Canadian cohort of cohorts. Canadian adults (n = 6645) recruited between 2014-2018 from the provinces of British Columbia, Alberta, Ontario, Quebec, and Nova Scotia, were studied, for whom averages of exposures to nitrogen dioxide (NO2), ozone (O3), and fine particulate matter (PM2.5) were estimated for the years 2008-2012. Carotid vessel wall volume (CWV) measured by magnetic resonance imaging (MRI). In adjusted linear mixed models, PM2.5 was not consistently associated with CWV (per 5 μg/m3 PM2.5; adjusted estimate = -8.4 mm3; 95% Confidence Intervals (CI) -23.3 to 6.48; p = 0.27). A 5 ppb higher NO2 concentration was associated with 11.8 mm3 lower CWV (95% CI -16.2 to -7.31; p<0.0001). A 3 ppb increase in O3 was associated with 9.34 mm3 higher CWV (95% CI 4.75 to 13.92; p<0.0001). However, the coarse/insufficient O3 resolution (10 km) is a limitation. In a cohort of healthy Canadian adults there was no consistent association between PM2.5 or NO2 and increased CWV as a measure of subclinical atherosclerosis by MRI. The reasons for these inconsistent associations warrant further study.

Quantitative evidence of micro-/nanoplastics in placental tissue of healthy Canadians revealed through pyrolysis gas chromatography-cyclic ion mobility mass spectrometry

Quantitative evidence of micro-/nanoplastics in placental tissue of healthy Canadians revealed through pyrolysis gas chromatography-cyclic ion mobility mass spectrometry

A Comparison of the Effects of Dairy Products with their Plant-based Alternatives on Metabolic Responses in Healthy Young Canadian Adults: a randomized cross-over study.

Plant-based food demand is rapidly increasing. However, the metabolic responses of plant proteins within their commercially available form remains unclear. Two randomized crossover experiments compared plant-based alternatives to dairy on postprandial glycemia, metabolic hormones, and appetite before and after a fixed size (12 kcal/kg body weight) pasta meal in sixteen healthy young adults (eight males and eight females). In experiment one, participants (22.8±2.3y) consumed one-serving of Greek yogurt (175g), cheddar cheese (30g), plant-based cheese (30g), or plant-based yogurt (175g). In experiment two, participants (22.3±2.4y) consumed one-serving (250 mL) of cow's milk, vanilla soy beverage or vanilla almond beverage, and (30 g) of cheddar cheese or plant-based cheese. Blood glucose, insulin, and appetite were measured at baseline, post-treatment, and following a fixed-size pasta meal (post-meal) within 15-30 min. In experiment two, C-peptide, GLP-1, and ghrelin were measured. Greek yogurt and cheddar cheese lowered post-meal blood glucose more than their plant-based alternatives (p <0.01) and post-treatment blood glucose was higher following almond beverage than cheddar cheese and plant-based cheese (p <0.01). In experiment 1, post-treatment insulin was higher after Greek yogurt than cheddar cheese and plant-based cheese and all treatments post-meal (p <0.02). Post-meal appetite was lower after plant-based yogurt than cheddar cheese and plant-based cheese (p <0.01). In experiment 2, post-treatment insulin was higher after almond beverage compared to all treatments (p <0.01) and post-meal GLP-1 was higher after milk than almond beverage (p =0.03). We conclude that the physiological functionality of plant-based alternatives as measured by blood glucose, insulin, C-peptide, and GLP-1 did not replicate the metabolic functions of dairy products.

Total sulfur amino acid requirements are higher during late gestation compared with early gestation in healthy Canadian pregnancies in a repeated-measures trial

BackgroundDietary Reference Intake (DRI) Recommendations for total sulfur amino acids (TSAAs; methionine + cysteine) during pregnancy are based on factorial calculations using data from adult males. To date, no data exist on TSAA requirements obtained directly during pregnancy. ObjectivesThe objective of this study was to examine whether TSAA requirements during early (11–20 wk) and late (31–40 wk) gestation in healthy females with singleton pregnancies are different than current recommendations, and different between early and late gestation using the indicator amino acid oxidation (IAAO) technique. MethodsTwenty-five females 20–40 y with a healthy singleton pregnancy were studied using the IAAO technique in a repeated measures design for a total of 70, 8-h d. On each study day a methionine test intake (range: 0–40 mg⋅kg−1⋅d−1) was provided in 8 hourly, isonitrogenous and isocaloric meals with cysteine excluded from the diet. Breath samples were collected at baseline and isotopic steady state of orally provided L-1-13C-Phenylalanine for measurement of phenylalanine oxidation. The requirement was determined using biphasic linear regression crossover analysis to identify a breakpoint in 13CO2 production, representing the estimated average requirement (EAR). ResultsThe TSAA requirement in healthy pregnant participants in early gestation was 11.1 mg⋅kg−1⋅d−1 {R2m = 0.79, R2c = 0.79; 95% confidence interval [CI] (8.9, 13.3 mg⋅kg−1⋅d−1)} and 15.0 mg⋅kg−1⋅d−1 (R2m = 0.72, R2c = 0.79; 95% CI [13.0, 17.0 mg⋅kg−1⋅d−1]) in late gestation. The difference between confidence intervals of the 2 breakpoints was = −3.9 ± 3.0, and statistically different. ConclusionsWe directly measured TSAA requirements in healthy pregnant mothers, and our findings suggest that requirements are lower than current DRI recommendations of 20 and 25 mg⋅kg−1⋅d−1, as the EAR, and Recommended Dietary Allowance, respectively. Late gestation TSAA needs are significantly different and increased 35% compared with early gestation. Recommendations for TSAA intake need to be tailored for gestational stage.This clinical trial was registered at clinicaltrials.gov as NCT04326322.

Adaptive immune responses to two-dose COVID-19 vaccine series in healthy Canadian adults ≥ 50 years: a prospective, observational cohort study

To evaluate immune responses to COVID-19 vaccines in adults aged 50 years and older, spike protein (S)-specific antibody concentration, avidity, and function (via angiotensin-converting enzyme 2 (ACE2) inhibition surrogate neutralization and antibody dependent cellular phagocytosis (ADCP)), as well as S-specific T cells were quantified via activation induced marker (AIM) assay in response to two-dose series. Eighty-four adults were vaccinated with either: mRNA/mRNA (mRNA-1273 and/or BNT162b2); ChAdOx1-S/mRNA; or ChAdOx1-S/ChAdOx1-S. Anti-S IgG concentrations, ADCP scores and ACE2 inhibiting antibody concentrations were highest at one-month post-second dose and declined by four-months post-second dose for all groups. mRNA/mRNA and ChAdOx1-S/mRNA schedules had significantly higher antibody responses than ChAdOx1-S/ChAdOx1-S. CD8+ T-cell responses one-month post-second dose were associated with increased ACE2 surrogate neutralization. Antibody avidity (total relative avidity index) did not change between one-month and four-months post-second dose and did not significantly differ between groups by four-months post-second dose. In determining COVID-19 correlates of protection, a measure that considers both antibody concentration and avidity should be considered.

Determining cardiovascular fitness normative reference values in a university aged Canadian population using maximal exercise testing

Abstract Study aim: Maximal oxygen uptake (VO2max) is the greatest rate at which the body can use oxygen and is an indicator of aerobic power. Although aerobic fitness is such a valuable determinant of health, there is limited research with established normative values for a healthy young adult Canadian population. The purpose of the study was to develop normative reference values for a Canadian young-adult population. Material and methods: 550 undergraduate student (280 male and 270 female) participants, with a mean body mass (BM) of 72.08 ± 15.05 kg, mean age of 21.16 ± 1.26 years old and mean height of 171.95 ± 10.25 cm completed a VO2max test using the Bruce treadmill protocol. Male and female classifications were established for the total exercise time in minutes and for the measured VO2max using percentiles and a seven-category classification system. Results: There were statistically significant differences between the sexes for VO2max values (p &lt; 0.001). The measured assessment for the healthy young Canadian adults showed a mean VO2max value of 40.90 ± 7.50 mL/kg/min for females and 49.89 ± 9.20 mL/kg/min for males. Females were able to withstand the exercise protocol for a mean of 11.92 ± 1.97 minutes, while males exercised for an average of 14.33 ± 2.40 minutes before the test was terminated. Conclusions: This study provides specific normative values for the aerobic fitness of a university aged Canadian population which can be used as reference values for cardiovascular health and fitness assessments.

Normative Reference Equations for Breathlessness Intensity during Incremental Cardiopulmonary Cycle Exercise Testing.

Rationale: Cardiopulmonary exercise testing (CPET) is the gold standard to evaluate exertional breathlessness, a common and disabling symptom. However, the interpretation of breathlessness responses to CPET is limited by a scarcity of normative data. Objectives: We aimed to develop normative reference equations for breathlessness intensity (Borg 0-10 category ratio) response in men and women aged ⩾40 years during CPET, in relation to power output (watts), oxygen uptake, and minute ventilation. Methods: Analysis of ostensibly healthy people aged ⩾40 years undergoing symptom-limited incremental cycle CPET (10 W/min) in the CanCOLD (Canadian Cohort Obstructive Lung Disease) study. Participants had smoking histories <5 pack-years and normal lung function and exercise capacity. The probability of each Borg 0-10 category ratio breathlessness intensity rating by power output, oxygen uptake, and minute ventilation (as an absolute or a relative value [percentage of predicted maximum]) was predicted using ordinal multinomial logistic regression. Model performance was evaluated by fit, calibration, and discrimination (C statistic) and externally validated in an independent sample (n = 86) of healthy Canadian adults. Results: We included 156 participants (43% women) from CanCOLD; the mean age was 65 (range, 42-91) years, and the mean body mass index was 26.3 (standard deviation, 3.8) kg/m2. Reference equations were developed for women and men separately, accounting for age and/or body mass. Model performance was high across all equations, including in the validation sample (C statistic for men = 0.81-0.92, C statistic for women = 0.81-0.96). Conclusions: Normative reference equations are provided to compare exertional breathlessness intensity ratings among individuals or groups and to identify and quantify abnormal breathlessness responses (scores greater than the upper limit of normal) during CPET.

Reference Interval Harmonization: Harnessing the Power of Big Data Analytics to Derive Common Reference Intervals across Populations and Testing Platforms.

Harmonization in laboratory medicine is essential for consistent and accurate clinical decision-making. There is significant and unwarranted variation in reference intervals (RIs) used by laboratories for assays with established analytical traceability. The Canadian Society of Clinical Chemists (CSCC) Working Group on Reference Interval Harmonization (hRI-WG) aims to establish harmonized RIs (hRIs) for laboratory tests and support implementation. Harnessing the power of big data, laboratory results were collected across populations and testing platforms to derive common adult RIs for 16 biochemical markers. A novel comprehensive approach was established, including: (a) analysis of big data from community laboratories across Canada; (b) statistical evaluation of age, sex, and analytical differences; (c) derivation of hRIs using the refineR method; and (d) verification of proposed hRIs across 9 laboratories with different instrumentation using serum and plasma samples collected from healthy Canadian adults. Harmonized RIs were calculated for all assays using the refineR method, except free thyroxine. Derived hRIs met proposed verification criterion across 9 laboratories and 5 manufacturers for alkaline phosphatase, albumin (bromocresol green), chloride, lactate dehydrogenase, magnesium, phosphate, potassium (serum), and total protein (serum). Further investigation is needed for some analytes due to failure to meet verification criteria in one or more laboratories (albumin [bromocresol purple], calcium, total carbon dioxide, total bilirubin, and sodium) or concern regarding excessively wide hRIs (alanine aminotransferase, creatinine, and thyroid stimulating hormone). We report a novel data-driven approach for RI harmonization. Findings support feasibility of RI harmonization for several analytes; however, some presented challenges, highlighting limitations that need to be considered in harmonization and big data analytics.

Pediatric reference interval verification for 16 biochemical markers on the Alinity ci system in the CALIPER cohort of healthy children and adolescents.

Special chemistry parameters are useful in the diagnosis and management of inherited disorders, liver disease, and immunopathology. Evidence-based pediatric reference intervals (RIs) are required for appropriate clinical decision-making and need to be verified as new assays are developed. This study aimed to evaluate the applicability of pediatric RIs established for biochemical markers on the ARCHITECT for use on newer Alinity assays. An initial method validation was completed for 16 assays, including precision, linearity, and method comparison. Sera collected from approximately 100 healthy children and adolescents as part of the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) were also analyzed on the Alinity c system. Percentage of results within established ARCHITECT RIs were calculated and considered verified if≥90 % fell within established limits. New RIs were established for three electrolytes, glucose, and lactate wherein no data were previously reported. Of the 11 assays for which CALIPER pediatric RIs were previously established on ARCHITECT assays, 10 met the verification criteria. Alpha-1-antitrypsin did not meet verification criterion and a new RI was established. For the other 5 assays, de novo RIs were derived following analysis of 139-168 samples from healthy children and adolescents. None required age- and sex-partitioning. Herein, pediatric RIs were verified or established for 16 chemistry markers in the CALIPER cohort on Alinity assays. Findings support excellent concordance between ARCHITECT and Alinity assays with one exception (alpha-1-antitrypsin) as well as robustness of age- and sex-specific patterns originally reported by CALIPER in healthy Canadian children and adolescents.

Comprehensive Pediatric Reference Limits for High-Sensitivity Cardiac Troponin I and NT-proBNP in the CALIPER Cohort.

Cardiac biomarkers have increasing application in pediatric populations, including congenital heart disease, myocarditis, and heart failure. Clinical practice is limited by evidence gaps in pediatric reference limits to inform clinical decision-making. The current study aimed to establish comprehensive pediatric reference limits for N-terminal (NT)-pro hormone brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI) in the CALIPER cohort of healthy children and adolescents. Analytical immunoassay performance was assessed through precision, linearity, and method comparison (Abbott Alinity ci system). Subsequently, approximately 200 serum samples collected from apparently healthy children (birth to 18 years) were analyzed for hs-cTnI and NT-proBNP. Reference limits (2.5th, 97.5th, and 99th percentiles) were established as per Clinical and Laboratory Standards Institute EP-28A3c guidelines with associated 90% confidence intervals. Of all pediatric serum samples analyzed, 46% had detectable hs-cTnI concentrations (limit of detection: 1.3 ng/L). Both hs-cTnI and NT-proBNP demonstrated markedly elevated neonatal concentrations with 99th percentiles of 55.8 and 1785 ng/L, respectively. No statistically significant age-specific differences were observed beyond 1 year of age across all cardiac biomarkers examined. No sex-specific association was observed between hs-cTnI and NT-proBNP concentration and adolescence. We report age-specific reference limits for hs-cTnI and NT-proBNP in a healthy Canadian cohort of children and adolescents measured using Alinity immunoassays for the first time. These data support the need for pediatric-specific interpretation to reduce misinformed clinical decision-making and calls to action larger cohort studies such that reference limits can be more robustly defined.

Association Between Insulin Resistance and the Inflammatory Marker C-reactive Protein in a Representative Healthy Adult Canadian Population: Results From the Canadian Health Measures Survey

ObjectivesInsulin resistance (IR) leads to type 2 diabetes mellitus. Multiple IR causes have been identified, including inflammation. This study determines the association between IR and the inflammatory marker C-reactive protein (CRP) in a healthy Canadian population and examines potential differences by sex and age. MethodsParticipants were adults with no self-reported history of diabetes, a glycated hemoglobin (A1C) of <6.5%, and a fasting blood glucose of <7 mmol/L, and who had participated in the Canadian Health Measures Survey, cycles 1 to 4 (2007–2015). IR was calculated using the Homeostasis Model of Insulin Resistance (HOMA-IR) assessment. The crude geometric mean HOMA-IR was calculated using a one-way analysis of variance. The association between CRP levels and HOMA-IR was examined using multivariate linear regression. ResultsA total of 4,024 eligible nondiabetic adults (1,994 [49.5%] men and 2,030 [50.4%] women) were identified. Eighty percent of the subjects were Caucasian. Among all subjects, 36% had a CRP of ≥2 mg/L. The crude geometric mean HOMA-IR was 1.33 in men and 1.24 in women. Participants with a CRP of <0.7 mg/L had a crude geometric mean HOMA-IR of 1.15 (1.13 to 1.16), compared with 1.41 (1.39 to 1.43) for those with a CRP of ≥2 mg/L. After adjusting for sex, age, race, high-density lipoprotein cholesterol, triglycerides, body mass index, smoking, and diastolic blood pressure, the HOMA-IR–CRP association remained significant. A positive trend for CRP values in men with increasing values of HOMA-IR was observed. However, this trend was not consistent with the increase in women’s CRP levels. ConclusionsElevated CPR levels are independently associated with IR in men. Prospective cohort studies can confirm the causal relationship between high CRP levels and IR and identify the underlying mechanisms.

LMS-based continuous reference percentiles for 14 laboratory parameters in the CALIPER cohort of healthy children and adolescents.

Marked physiological changes in growth and development present challenges in defining pediatric reference intervals for biomarkers of health and disease. Lambda, Mu, and Sigma (LMS)-based statistical modeling provides a continuous normal distribution by negating skewness and variation, and is commonly used to establish growth charts. Such LMS reference curves are suggested toenhance laboratory test result interpretation. The currentstudy establishes LMS-based continuous reference percentiles for 14 biomarkers in the CALIPER cohort of healthy children and adolescents. Data from healthy children and adolescents aged 1-<19years were used to establish continuous reference percentiles using a novel LMS-based statistical method, including 2.5th, 25th, 50th, 75th, and 97.5th percentiles. The LMS approach applies a Box-Cox data transformation and summarizes continuous distributions by age via three curves: skewness (Lambda), median (Mu), and coefficient of variation (Sigma). LMS-based percentiles and z-scores were generated for 14 common pediatric biomarkers that demonstrate dynamic concentration patterns with age (e.g., alkaline phosphatase) and/or wherein the magnitude of difference fromthe population mean may be clinically relevant (e.g.,triglycerides). The LMS model captured age- and sex-specific distributions accurately and was not substantially influenced by outlying points. This is the first study to establish LMS-based continuous reference percentiles for biochemical markers in a healthy Canadian pediatric population. The current LMS-based approach builds upon previous continuous reference interval models by providing graded percentiles toimprove test result interpretation, particularly with repeated measures over time. This method may assist infacilitating a patient-centered approach to laboratory medicine.

Engagement Analysis of Canadian Public Health and News Media Facebook Posts and Sentiment Analysis of Corresponding Comments during COVID-19

During the COVID-19 pandemic, key stakeholders have used social media to rapidly disseminate essential information to the public to help them make informed health-related decisions. Our research examined how the public responded to official actors’ Facebook posts during COVID-19 and examined the comment sentiment and post engagement rates. CBC News and CTV News received a greater proportion of negative comments and a lower average post engagement rate compared with Healthy Canadians. Additionally, the proportion of negative and positive comments varied over time for all sources; however, over 30% of the comments for all three actors were consistently negative. Key stakeholders should monitor the public’s response to their social media posts and adapt their messages to increase the effectiveness of their crisis communication efforts to encourage the adoption of protective measures.

Medical student wellness in Canada: time for a national curriculum framework.

There is substantial evidence showing that medical student wellness is a worsening problem in Canada. It is apparent that medical students’ wellness deteriorates throughout their training. Medical schools and their governing bodies are responding by integrating wellness into competency frameworks and accreditation standards through a combination of system- and individual-level approaches. System-level strategies that consider how policies, medical culture, and the “hidden curriculum” impact student wellness, are essential for reducing burnout prevalence and achieving optimal wellness outcomes. Individual-level initiatives such as wellness programming are widespread and more commonly used. These are often didactic, placing the onus on the student without addressing the learning environment. Despite significant progress, there is little programming consistency across schools or training levels. There is no wellness curriculum framework for Canadian undergraduate medical education that aligns with residency competencies. Creating such a framework would help align individual- and system-level initiatives and smooth the transition from medical school to residency. The framework would organize goals within relevant wellness domains, allow for local adaptability, consider basic learner needs, and be learner-informed. Physicians whose wellness has been supported throughout their training will positively contribute to the quality of patient care, work environments, and in sustaining a healthy Canadian population.

P.031 A Rare Canadian Case of Cervical Pyomyosistis Presenting as Occipital Neuralgia

Background: Pyomyositis is an infectious disease usually encountered in tropical regions. It typically occurs in immunocompromised hosts and most commonly affects lower limb muscles. Our patient was a healthy Canadian with an atypical presentation of cervical pyomyositis. Methods: We report a case of a healthy 22-year old woman presenting to the emergency department with unprovoked severe bilateral cervico-occipital pain and nuchal rigidity. She remained afebrile. Review of the literature was conducted to search for similar presentations. Results: A Computed Tomography scan of the head and neck demonstrated the presence of a ring enhancing lesion in the semispinalis capitis muscle extending from the occiput to the C4 level. The abscess was surgically drained and cultures grew staphylococcus aureus. The patient rapidly improved on intravenous antibiotics. Literature review revealed this to be the first Canadian case of cervical pyomyositis. Conclusions: Cervical pyomyositis can be complicated by local destruction of the vertebrae, septic shock, endocarditis, septic emboli, brain abscess or rhabdomyolysis. Early diagnosis and source control is necessary to reduce the risk of morbidity. Therefore, it is important to consider this rare disease in the differential diagnosis of cervicalgia even in healthy immunocompetent patients.

Continuous reference curves for common hematology markers in the CALIPER cohort of healthy children and adolescents on the Sysmex XN-3000 system.

Clinicians and healthcare professionals rely heavily on health-associated standards, such as reference intervals (RIs), for appropriate laboratory test result interpretation. RIs are commonly partitioned into discrete age/sex bins based on statistical and/or clinical significance. In pediatric hematology, such partitioning does not adequately represent complex variation in analyte concentrations throughout maturation. The objective of this study was to establish continuous RIs for common hematological parameters in the healthy pediatric Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort. Data from healthy CALIPER children and adolescents (6months-<19years) were used to generate continuous RIs (ie, 2.5th and 97.5th quantiles) for 19 hematological parameters. Continuous curves were statistically established with nonparametric quantile regressions. Flagging rate analysis was completed for the established continuous upper and lower reference limits and subsequently compared to previously published discrete CALIPER reference intervals for all parameters. Continuous RIs were established for 19 hematology parameters, where seven required sex-specific reference curves. Based on flagging rate assessment, continuous RIs appear to more accurately estimate hematological reference limits over the pediatric age range, especially for analytes with complex age- and sex-specific reference value patterns. This is the first study to generate continuous RIs for a breadth of hematological markers in a healthy pediatric Canadian population. The increased power of continuous reference intervals to accurately estimate the complex relationship between hematological analyte concentration and age during a time of extensive growth and development is expected to improve laboratory test result interpretation and, subsequently, pediatric clinical decision-making.

Continuous reference intervals for 19 endocrine, fertility, and immunochemical markers in the CALIPER cohort of healthy children and adolescents

BackgroundReference intervals are traditionally partitioned into discrete ranges by major covariates such as age and sex. However, discrete reference intervals often oversimplify the complex relationship between analyte concentration and age. Continuous reference intervals have been suggested to more accurately represent this complex relationship, particularly in pediatrics. The objective of this study was to establish continuous reference intervals for endocrine, fertility, and additional immunochemical parameters in the CALIPER cohort of healthy children and adolescents. MethodsContinuous reference intervals from 1 to 18.5 years of age were established using retrospective CALIPER data collected from healthy Canadian children and adolescents. Continuous reference intervals (2.5th and 97.5th percentiles) were determined for 19 parameters by nonparametric quantile regression. Total and yearly flagging rates were calculated for the upper and lower continuous reference limits and compared to previously published partitioned reference limits. ResultsContinuous reference intervals were established for 19 endocrine, fertility, and additional immunochemical parameters, with 11 requiring sex-specific reference curves. Continuous reference intervals assessed both visually and by flagging rate analysis more accurately represented the relationship between analyte concentration and age, particularly for parameters with complex reference value patterns. ConclusionThis is the first comprehensive report to establish continuous reference intervals for several immunochemical parameters including endocrine and fertility markers in a healthy paediatric Canadian cohort. The ability of continuous reference intervals to provide a better estimate of age-related changes in reference values suggest their potential to improve paediatric laboratory test result interpretation and clinical decision-making.

The impact of publicly funded rotavirus immunization programs on Canadian children.

In 2008, the National Advisory Committee on Immunization recommended routine rotavirus immunizations in healthy Canadian infants. Over the following seven years, eight provinces and two territories introduced the rotavirus vaccine into their publicly funded immunization programs. Assess the burden of rotavirus infections before and after implementation of publicly funded immunization programs. We analyzed laboratory-confirmed community cases of rotavirus reported to the National Enteric Surveillance Program and hospitalizations of children younger than three years old from 2007 to 2017 with rotavirus diagnosis-specific ICD-10 codes. Rates of illness were calculated for each province for the two years prior to and after implementation of public funding of the vaccine. The year of implementation was not included to accommodate the uptake period of the vaccine. Age-specific rates were assessed in jurisdictions where five years of data were available the year after the vaccine was publicly funded. The pre-post and difference-in-difference (DID) methodologies were applied to hospital discharge data to evaluate changes between the funding and non-funding jurisdictions. Community cases of laboratory-confirmed rotavirus infection reported to the National Enteric Surveillance Program declined by 54% between 2010 and 2017. Rates of hospital discharges decreased significantly among children in six provinces after the adoption of the rotavirus vaccine. Hospital discharge rates in Alberta, Manitoba, Ontario and Prince Edward Island dropped between 53% and 71%, and by 75% for British Columbia and Saskatchewan. Public funding of the rotavirus vaccine appeared to lead to significant reductions in laboratory-confirmed rotavirus cases reported to the National Enteric Surveillance Program and in the rates of rotavirus gastroenteritis-related hospital discharges.