Racial, ethnic and socioeconomic disparities in diagnosis, treatment, and survival of patients with breast cancer.

BACKGROUND: The objective of this study was to determine the influence of race/ethnicity and socioeconomic status (SES) on breast cancer outcomes. METHODS: A retrospective analysis was performed of Non-Hispanic Black (NHB), Non-Hispanic White (NHW), and Hispanic patients with non-metastatic breast cancer in the SEER cancer registry between 2007 and 2016. RESULTS: A total of 382,975 patients were identified. On multivariate analysis, NHB (OR 1.18, 95%CI: 1.15-1.20) and Hispanic (OR 1.20, 95%CI: 1.17-1.22) patients were more likely to present with higher stage disease than NHW patients. There was an increased likelihood of not undergoing breast-reconstruction for NHB (OR 1.07, 95%CI: 1.03-1.11) and Hispanic patients (OR 1.60, 95%CI 1.54-1.66). NHB patients had increased hazard for all-cause mortality (HR: 1.13, 95%CI 1.10-1.16). All-cause mortality increased across SES categories (lower SES: HR 1.33, 95%CI 1.30-1.37, middle SES: HR 1.20, 95%CI 1.17-1.23). CONCLUSIONS: This population-based analysis confirms worse disease presentation, access to surgical therapy, and survival across racial, ethnic, and socioeconomic factors. These disparities were compounded across worsening SES and insurance coverage.

Delivery of Virtual Care in Oncology: Province-Wide Interprofessional Consensus Statements Using a Modified Delphi Process.

Virtual cancer care (i.e., teleoncology) was rapidly adopted during the COVID-19 pandemic to meet the needs of patients with cancer. However, there is a paucity of guidance for clinicians regarding virtual cancer care. We sought to develop consensus-based statements to guide the optimal provision of virtual care for clinicians caring for patients with cancer, using a modified Delphi consensus process with a 29-member panel consisting of an interprofessional group of clinicians caring for patients with cancer and patient representatives. The consensus process consisted of two rounds and one synchronous final consensus meeting. At the end of the modified Delphi process, 62 of 62 statements achieved consensus. Fifty-seven statements reached consensus in the first round of the process. Concerns regarding the ability to convey difficult news virtually and maintaining similar standards as in-person care without disproportionate strain on clinicians and patients were addressed in the consensus process. We achieved interprofessional consensus on virtual cancer care practices. Further research examining the impact of virtual cancer care on person-centred and clinical outcomes are needed to inform practices during the COVID-19 pandemic and beyond.

Cancer Treatment During COVID-19: A Qualitative Analysis of Patient-Perceived Risks and Experiences with Virtual Care.

During the COVID-19 pandemic, most cancer centers shifted from in-person to virtual cancer care to curb community spread and ensure care continuity. This qualitative descriptive study aimed to understand cancer patient-perceived risks related to COVID-19 and cancer treatment, as well as the patient-perceived and experienced value of virtual care. From June to August 2020, focus groups were conducted with patients under active management or observation for a diagnosed malignancy in Toronto, Canada. A thematic analysis of six focus groups found that most participants worried more about treatment delays than they did about COVID-19 infection. Despite some concern about COVID-19 exposure in the hospital, care delays contributed to increased anxiety among participants who already subscribed to strict safety measures in their everyday lives. Most participants accepted virtual care for some appointment types; however, preference for in-person care was found to sustain the humanistic and therapeutic aspects of cancer care that many participants valued. Nuances in the appropriateness and adequacy of virtual cancer care still need exploration. Preserving the humanistic aspects of care is of paramount importance.

SARS-CoV-2 Testing for Asymptomatic Patients with Cancer Prior and during Treatment: A Single Centre Experience.

Patients with cancer are more vulnerable to severe COVID-19. As a result, routine SARS-CoV-2 testing of asymptomatic patients with cancer is recommended prior to treatment. However, there is limited evidence of its clinical usefulness. The objective of this study is to evaluate the value of routine testing of asymptomatic patients with cancer. Asymptomatic patients with cancer attending Odette Cancer Centre (Toronto, ON, Canada) were tested for SARS-CoV-2 prior to and during treatment cycles. Results were compared to positivity rates of SARS-CoV-2 locally and provincially. All 890 asymptomatic patients tested negative. Positivity rates in the province were 1.5%, in hospital were 1.0%, and among OCC's symptomatic cancer patients were 0% over the study period. Given our findings and the low SARS-CoV-2 community positivity rates, we recommend a dynamic testing model of asymptomatic patients that triggers testing during increasing community positivity rates of SARS-CoV-2.

Complex biological patterns of hematology parameters in childhood necessitating age- and sex-specific reference intervals for evidence-based clinical interpretation.

INTRODUCTION: Hematology laboratory parameters are among the most routinely ordered tests in support of adult and pediatric care. However, appropriate interpretation of test results has been a challenge in pediatrics since accurate and up-to-date reference intervals that reflect the dynamic physiological changes associated with growth and development have not been available. Critical gaps continue to exist in pediatric hematology reference intervals for modern laboratory platforms. To address this gap, this study establishes age- and sex-specific reference intervals for 25 hematology parameters in the CALIPER cohort of healthy children and adolescents using a common platform, the Sysmex XN-3000 analytical system. METHODS: Fresh whole blood samples collected from a total of 641 healthy children and adolescents (birth to <21 years) with informed consent were analyzed for 25 hematological parameters on the Sysmex XN-3000 Hematology Analyzer. Age- and sex-specific reference standards were calculated based on Clinical and Laboratory Standards Institute guidelines. RESULTS: Of the 25 analytes assessed, 19 required age-partitioning and seven required sex-partitioning (ie, red blood cell count, hemoglobin, hematocrit, mean corpuscular volume, red blood cell distribution width-SD, red blood cell distribution width-CV, and monocyte percentage). Age- and sex-specific differences mostly coincided with the onset of puberty. CONCLUSION: This study establishes a comprehensive database of pediatric reference intervals for hematology parameters in the CALIPER cohort using the widely used Sysmex XN-3000 analytical platform. These data highlight the dynamic hematological profile observed in healthy children and adolescents and the need for reference interval stratification by age and sex.

CALIPER Hematology Reference Standards (I).

OBJECTIVES: Accurate hematologic test interpretation based on normative reference standards is critical to ensure appropriate clinical decision making. However, healthy pediatric reference data for most hematology parameters are lacking. To address this gap, this study establishes age- and sex-specific hematologic reference standards in the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort of healthy children and adolescents. METHODS: Fresh whole blood samples collected from a total of 566 healthy children and adolescents (birth to <21 years) with informed consent were analyzed for 47 hematologic parameters on the Beckman Coulter DxH 900. Age- and sex-specific reference standards were calculated based on the Clinical and Laboratory Standards Institute guidelines. RESULTS: Reference value distributions for most hematology parameters demonstrated dynamic changes across the pediatric age range with significant age-specific differences observed for 39 of the 47 parameters examined. Sex-specific differences were also observed for eight hematologic parameters, primarily during and after puberty. CONCLUSIONS: This study establishes a robust database of pediatric reference standards for 47 hematologic parameters in the CALIPER cohort for the first time. These comprehensive reference value data sets report potentially important and physiologically relevant trends in hematologic markers, clearly demonstrating the need for pediatric reference standards for hematologic test interpretation.

CALIPER Hematology Reference Standards (II).

OBJECTIVES: The objective of this study was to establish comprehensive age- and sex-specific reference intervals for hematologic parameters in the CALIPER cohort of healthy children and adolescents. METHODS: A total of 536 healthy children and adolescents (birth to 21 years) were recruited with informed consent, and whole blood samples were analyzed for 27 hematologic parameters on the Beckman Coulter DxH 520 system. Age- and sex-specific pediatric reference standards were established. Reference values obtained on the DxH 520 were also compared with data obtained on a larger laboratory-based instrument (DxH 900). RESULTS: Most hematologic parameters showed significant age- and/or sex-specific changes during growth and development. Of the 27 hematologic parameters, all except four (mean corpuscular hemoglobin concentration, basophil percentage, low hemoglobin density, immature cell percentage) required age partitioning, and eight required sex partitioning. CONCLUSIONS: This study establishes a robust pediatric hematology reference database that will assist in more accurate test result interpretation. Our data clearly demonstrate significant variation in hematologic parameter concentrations in children and adolescents, necessitating the use of pediatric-specific reference standards.

Influence of ethnicity on biochemical markers of health and disease in the CALIPER cohort of healthy children and adolescents.

Background Accurate pediatric reference intervals (RIs) for laboratory tests determined in a healthy pediatric population are essential for correct laboratory test interpretation and clinical decision-making. In pediatrics, RIs require partitioning by age and/or sex; however, the need for partitioning based on ethnicity is unclear. Here, we assessed the influence of ethnicity on biomarker concentrations in the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort of healthy children and adolescents and compared the results with the National Health and Nutrition Examination Survey (NHANES). Methods A total of 52 biomarkers were measured in a multiethnic population of 846-1179 healthy children (aged 5 to <19 years) upon informed consent. Biomarker concentrations were retrospectively compared between four major ethnic groups (i.e. Black, Caucasian, East Asian, and South Asian, determined by parental ethnicity). Retrospective results were verified prospectively using an additional 500 healthy pediatric samples with equal sample size across ethnicities. Ethnic-specific differences were assessed based on statistical significance and biological and analytical variations. Appropriate age-, sex-, and ethnic-specific RIs were calculated. Results Ethnic-specific differences were not observed for 34 biomarkers examined in the retrospective analysis, while 18 demonstrated statistically significant ethnic differences. Among these, seven analytes demonstrated ethnic-specific differences in the prospective analysis: vitamin D, amylase, ferritin, follicle-stimulating hormone (FSH), immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM). Analysis of select NHANES data confirmed CALIPER findings. Conclusions This is the first comprehensive Canadian pediatric study examining ethnic-specific differences in common biomarkers. While the majority of biomarkers did not require ethnic partitioning, ethnic-specific RIs were established for seven biomarkers showing marked differences. Further studies in other populations are needed to confirm our findings.

Marked Influence of Adiposity on Laboratory Biomarkers in a Healthy Cohort of Children and Adolescents.

BACKGROUND: The prevalence of pediatric obesity is increasing worldwide and strongly associates with metabolic abnormalities, including inflammation, insulin resistance, and dyslipidemia. This study assessed the influence of 3 measures of adiposity on levels of routinely assessed biochemical markers in apparently healthy children and adolescents. METHODS: The influence of adiposity on 35 biochemical markers was examined in the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort of healthy children and adolescents by comparing serum biomarker levels between subjects with a normal weight, overweight, and obese body mass index (BMI). The cohort comprised 1332 subjects 5.1 to 19.0 years of age with a BMI ranging from 13.4 to 65.0 kg/m2. The association between each biochemical marker and BMI, waist circumference, and waist-to-height ratio z-scores was assessed, while adjusting for age and sex. Reference intervals were established for all biochemical markers before and after removing overweight/obese subjects. RESULTS: In children and adolescents, levels of 13 routinely assessed biochemical markers, including alanine aminotransferase, apolipoprotein B, complement components 3 and 4, cholinesterase, high sensitivity C-reactive protein, gamma-glutamyl transferase, haptoglobin, high-density lipoprotein cholesterol, iron, transferrin, triglycerides, and uric acid, were significantly different between BMI categories. BMI, waist circumference, and/or waist-to-height ratio were significantly associated with the serum concentration of 24 of the 35 markers examined, after adjusting for age and sex. CONCLUSIONS: Excess adiposity significantly influences circulating levels of routinely assessed laboratory markers, most notably liver enzymes, lipids/lipoproteins, inflammatory markers, and uric acid in children and adolescents. Although it is unknown whether altered biochemical marker levels in subjects with overweight/obesity reflect health or indolent disease, clinicians should be aware of the effect of weight status on several laboratory tests.

Pediatric reference intervals for clinical chemistry assays on Siemens ADVIA XPT/1800 and Dimension EXL in the CALIPER cohort of healthy children and adolescents.

INTRODUCTION: Accurate reference intervals (RIs) are essential for clinical interpretation of laboratory test results; however, major gaps exist in pediatric RIs. The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has established age- and sex-specific pediatric RIs on various analytical platforms. The current study expands the CALIPER database by establishing age- and sex-specific RIs for biochemical assays on Siemens ADVIA XPT/1800 and Dimension EXL Systems. METHODS: Serum samples from a total of 909 and 867 healthy children and adolescents (ages 0-<19 y) were tested on ADVIA XPT/1800 and Dimension EXL systems, respectively. Age- and/or sex-specific RIs were calculated for a total of 54 biochemical assays. RESULTS: Serum concentrations of several biomarkers remained relatively constant across the pediatric age range and similar between sexes, including sodium and triglycerides. Other biomarkers, such as alkaline phosphatase and creatinine showed both age and sex differences. Furthermore, immunoglobulin A and iron showed only age differences. DISCUSSION: We established RIs for creatine kinase, random glucose, total iron binding capacity, and several electrolytes for the first time using the CALIPER cohort. Overall, pediatric RIs established in the current study will allow for more accurate laboratory test interpretation worldwide using Siemens chemistry assays.

Influence of ethnicity on population reference values for biochemical markers.

Reference intervals (RIs) for biochemical and hematological markers determined using healthy adult and/or pediatric populations are vital for clinical interpretation of laboratory test results. Most clinical laboratories commonly use age- and sex-specific RIs, but the effect of ethnicity as a covariate is often overlooked. Ethnic differences in serum biomarker concentrations can occur as a result of genetic and environmental factors, while the degree to which each factor influences serum levels depends on the specific biomarker. Numerous studies have investigated ethnic differences in routine chemistry, fertility, endocrine, cancer, and hematological markers, as well as in vitamins and carotenoids, in children, adolescents and adults. In the present review, we summarize and discuss ethnic-specific differences observed for these laboratory markers and their potential impact on the clinical interpretation of laboratory test results. We categorized the available data into seven major ethnic groups (i.e. Black, Caucasian, East Asian, Hispanic, South Asian, South East Asian, and West Asian) for ease of comparison. While certain biomarkers could not be compared between ethnic groups because of insufficient information or contradictory results between studies, significant differences between ethnic groups were reported by one or more studies for most of the biomarkers included in this review. The clinical significance of these differences and the potential need for ethnic-specific RIs for certain biochemical markers are also discussed.

CLSI-based transference and verification of CALIPER pediatric reference intervals for 29 Ortho VITROS 5600 chemistry assays.

BACKGROUND: Evidence-based reference intervals (RIs) are essential to accurately interpret pediatric laboratory test results. To fill gaps in pediatric RIs, the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) project developed an age- and sex-specific pediatric RI database based on healthy pediatric subjects. Originally established for Abbott ARCHITECT assays, CALIPER RIs were transferred to assays on Beckman, Roche, Siemens, and Ortho analytical platforms. This study provides transferred reference intervals for 29 biochemical assays for the Ortho VITROS 5600 Chemistry System (Ortho). METHODS: Based on Clinical Laboratory Standards Institute (CLSI) guidelines, a method comparison analysis was performed by measuring approximately 200 patient serum samples using Abbott and Ortho assays. The equation of the line of best fit was calculated and the appropriateness of the linear model was assessed. This equation was used to transfer RIs from Abbott to Ortho assays. Transferred RIs were verified using 84 healthy pediatric serum samples from the CALIPER cohort. RESULTS: RIs for most chemistry analytes successfully transferred from Abbott to Ortho assays. Calcium and CO2 did not meet statistical criteria for transference (r2<0.70). Of the 32 transferred reference intervals, 29 successfully verified with approximately 90% of results from reference samples falling within transferred confidence limits. Transferred RIs for total bilirubin, magnesium, and LDH did not meet verification criteria and are not reported. CONCLUSIONS: This study broadens the utility of the CALIPER pediatric RI database to laboratories using Ortho VITROS 5600 biochemical assays. Clinical laboratories should verify CALIPER reference intervals for their specific analytical platform and local population as recommended by CLSI.

Pediatric Reference Intervals for Biochemical Markers: Gaps and Challenges, Recent National Initiatives and Future Perspectives.

Reference intervals provide valuable information to medical practitioners in their interpretation of quantitative laboratory test results, and are critical in the assessment of patient health and in clinical decision-making. The reference interval serves as a health-associated benchmark with which to compare an individual test result. While the concept of reference intervals and their utility appear straightforward, the process of establishing accurate and reliable reference intervals is considerably complex and involved. Currently, many pediatric laboratory tests are inappropriately interpreted using reference intervals derived from either adult populations, hospitalized pediatric populations, or from outdated and/or inaccurate technology. Thus, many pediatric reference intervals used in diagnostic laboratories are incomplete and may be inappropriate for clinical use. The use of inappropriate reference intervals impacts clinical decision-making and has potential detrimental effects on the quality of patient healthcare including misdiagnosis, delayed diagnosis, inappropriate treatments, and patient risk. These are critical gaps in pediatric healthcare and it is imperative to update and establish appropriate reference intervals for pediatric populations based on specific age- and sex-stratifications. In the present review, specific issues, challenges and deficiencies in pediatric reference intervals for biochemical markers will be discussed. Early studies using hospitalized patients will be examined, followed by a review of recent national and global initiatives on establishing reference intervals from healthy pediatric population. We will highlight the achievements and milestones of the Canadian CALIPER project, including the establishment of a comprehensive biobank and database which has addressed several of these critical gaps. CALIPER's mandate is to establish and provide comprehensive, up-to-date pediatric reference intervals to all biochemical markers of pediatric disease. CALIPER has also begun knowledge translation initiatives to disseminate its data via peer-reviewed publication, an online database, and a smartphone application to allow greater access to CALIPER pediatric reference interval data. Finally, limitations, future perspectives and harmonization of pediatric reference intervals to improve pediatric diagnostics in Canada and worldwide will be discussed.

Mitochondrial Bioenergetics and Fiber Type Assessments in Microbiopsy vs. Bergstrom Percutaneous Sampling of Human Skeletal Muscle.

Microbiopsies of human skeletal muscle are increasingly adopted by physiologists for a variety of experimental assays given the reduced invasiveness of this procedure compared to the classic Bergstrom percutaneous biopsy technique. However, a recent report demonstrated lower mitochondrial respiration in saponin-permeabilized muscle fiber bundles (PmFB) prepared from microbiopsies vs. Bergstrom biopsies. We hypothesized that ADP-induced contraction (rigor) of smaller length microbiopsy PmFB causes a greater reduction in maximal respiration vs. Bergstrom, such that respiration could be increased by a myosin II ATPase-inhibitor (Blebbistatin; BLEB). Eleven males and females each received a 2 mm diameter percutaneous microbiopsy and a 5 mm diameter Bergstrom percutaneous biopsy in opposite legs. Glutamate/malate (5/0.5 mM)-supported respiration in microbiopsy PmFB was lower than Bergstrom at submaximal concentrations of ADP. 5 µM BLEB reduced this impairment such that there were no differences relative to Bergstrom ± BLEB. Surprisingly, pyruvate (5 mM)-supported respiration was not different between either biopsy technique ±BLEB, whereas BLEB increased succinate-supported respiration in Bergstrom only. H2O2 emission was lower in microbiopsy PmFB compared to Bergstrom PmFB in the presence of BLEB. Microbiopsies contained fewer type I fibers (37 vs. 47%) and more type IIX fibers (20 vs. 8%) compared to Bergstrom possibly due to sampling site depth and/or longitudinal location. These findings suggest that smaller diameter percutaneous biopsies yield lower glutamate-supported mitochondrial respiratory kinetics which is increased by preventing ADP-induced rigor with myosin inhibition. Microbiopsies of human skeletal muscle can be utilized for assessing mitochondrial respiratory kinetics in PmFB when assay conditions are supplemented with BLEB, but fiber type differences with this method should be considered.