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

ObjectivesThe 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 methodsBased 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.ResultsIn 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.ConclusionsThis 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.     

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

BackgroundEvidence-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).MethodsBased 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.ResultsRIs 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.ConclusionsThis 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.     

Plasma total adiponectin levels in pediatrics: Reference intervals calculated as a continuous variable of age

Objective

Plasma total Adiponectin (tAN) is a novel biomarker with interesting potentialities in pediatrics. Age-related intervals are needed for the correct interpretation of results. In this study, we calculated the reference values for tAN using a large number of results derived from pediatric patients.

Design and methods

tAN was determined by ELISA in more than 4000 samples and the results collected in the Laboratory Information System were used for the calculation of reference intervals.

Results

tAN reference values for the different age intervals were obtained and age related tAN reference intervals were calculated. Some differences were observed in males and females. In obese children, no correlation between age and tAN could be observed. On the contrary, significant relations were observed in the total group of patients and in healthy control subjects. For this reason, the parameters of the equations to calculate tAN reference values using age as a continuous variable were defined.

Conclusion

The use of continuous tAN reference intervals, calculated on age, should be considered a useful laboratory tool, at least in the pediatric population, for those biomarkers whose reference values have been shown to change from birth to the late adolescence.     

Redefining normal bone and mineral clinical biochemistry reference intervals for healthy infants in Canada

Background

Few normative data exist for routine clinical chemistry in healthy term infants, that is, during a time of rapid development. Biochemical markers are significantly affected by these physiological changes and the lack of appropriate reference intervals may impede diagnostics in infants.

Objective

To define reference intervals for calcium, phosphate, creatinine, and alkaline phosphatase in infants from 1 to 12 months of age.

Design and methods

This was an unblinded secondary analysis of 132 breastfeeding infants participating in a vitamin D₃ supplementation trial (400–1600 IU/d) followed prospectively until 1 year of age (NCT00381914). Serial non-fasting capillary and spot urine samples were collected for the measurement of plasma calcium, phosphate, creatinine, and alkaline phosphatase; urinary calcium, phosphate and creatinine (DxC600 Beckman Coulter); and whole-blood ionized calcium (ABL 725 Radiometer). All visits were conducted at McGill University in Montréal, Canada.

Results

All analytes changed significantly over time (p < 0.05), but there was no effect of sex. From 1 to 12 months, values decreased for whole-blood ionized calcium; plasma calcium, phosphate, and alkaline phosphatase; and urinary calcium:creatinine. Plasma creatinine increased. For some analytes, particularly calcium and alkaline phosphatase, values were often above the ‘typical’ adult or older child reference limits. Smoothed centile curves (LMS method) were developed to fill existing gaps in normative data for these analytes.

Conclusions

Most analytes showed a significant change from 1 to 12 months, confirming the need for age-specific reference values. These data can assist in the generation of new reference intervals for healthy term infants and ultimately improve the care of children.     

Canadian Laboratory Initiative on Pediatric Reference Interval Database (CALIPER): Pediatric reference intervals for an integrated clinical chemistry and immunoassay analyzer, Abbott ARCHITECT ci8200

Objectives

A comprehensive set of age- and gender-specific pediatric reference intervals is essential for accurate interpretation of laboratory tests in a pediatric setting.

Design and methods

1459 serum/plasma from children attending select outpatient clinics and deemed to be metabolically stable, were collected from five age groups; 0-12 months, 1-5 years, 6-10 years, 11-14 years and 15-20 years. Samples were analyzed for 24 chemistries and 15 immunoassays on ARCHITECT ci8200.

Results

Reference intervals were established according to CLSI/IFCC C28-P3 guidelines by the Robust statistical method. The ranges reflect the central 95% confidence intervals for the population tested. Age and gender were partitioned using the Harris-Boyd method.

Conclusions

While these intervals are ci8200 method specific, they not only provide robust intervals for users of this system but are also useful for any laboratory requiring pediatric intervals if they can be shown to be transferable and if validated for the local patient population.     

Continuous reference intervals for 38 biochemical markers in healthy children and adolescents: Comparisons to traditionally partitioned reference intervals

BackgroundReference intervals have traditionally been partitioned by age based on statistical significance and physiological relevance. However, analyte concentration does not change abruptly with age, but rather dynamically. In this study, we establish biochemical marker continuous reference intervals for a Canadian population using healthy pediatric reference individuals and compare these to partitioned reference intervals.MethodsContinuous reference intervals spanning 1–18.5 years of age were established using data from healthy CALIPER children and adolescents aged 6 months- < 19 years. Continuous reference intervals (i.e. 2.5th and 97.5th quantiles) were generated by nonparametric quantile regression via penalized splines with non-crossing constraints. Abnormal flagging rates of established continuous reference intervals were compared to previously established age-partitioned CALIPER reference intervals for five biochemical markers using internal (CALIPER) and external (i.e. Canadian Health Measures Survey (CHMS)) datasets.ResultsContinuous reference intervals were determined for 38 biochemical markers, with 21 markers requiring sex-specific reference intervals. Despite similar total flagging rates to partitioned reference intervals, continuous reference intervals appeared to provide a more consistent and accurate estimation of reference limits for biomarkers with more complex age-related changes, including alkaline phosphatase and phosphate.ConclusionsThis is the first report of continuous biochemical marker reference intervals based on a healthy Canadian pediatric population. Reference limit point estimates based on continuous reference intervals are provided to aid clinical implementation. Continuous reference intervals offer a better estimation of dynamic changes in biochemical marker reference values with age, resulting in improved laboratory test result interpretation and clinical decision making in pediatrics.     

Reference intervals for serum creatinine levels in the healthy geriatric population

Background

There are few reliable reference values of enzymatically assayed serum creatinine (Scr) levels categorized within a small age interval in the healthy geriatric population. The aim of this study was to establish the reference intervals (RIs) for Scr in the elderly population.

Methods

Healthy, elderly Chinese Han ethnic individuals aged between 60 and 89 years old were recruited for this study. We stratified the reference individuals by gender and age (60–69, 70–79 and 80–89 years), and the Scr values were measured by an enzymatic method. The central 95 percentile RIs were determined using non-parametric statistical methods.

Results

The Scr values in the elderly population show a Gaussian distribution and age/sex related differences. The RIs for Scr in the reference population with respect to age (ranges of 60–69, 70–79 and 80–89 years) were 52.9–94.5, 57.3–106.2 and 59.0–110.8 μmol/L for males, respectively, and 44.3–75.4, 47.1–85.5 and 45.1–90.9 μmol/L for females, respectively.

Conclusions

We have established the RIs for Scr measured with an enzymatic method in the healthy Chinese Han ethnic elderly population, which can provide a reference for both clinical and laboratory studies.     

Establishment of hormone reference intervals for infants born < 30 weeks' gestation

Objective

Preterm infants, especially those born very preterm (< 32 weeks' gestation), suffer a number of morbidities. Immaturity of the endocrine system and its potential impact on morbidity is the subject of numerous studies. Hormone concentrations are sometimes measured in very preterm infants, however there are little normative data available to be able to interpret the results. The aim of this study was to describe age appropriate hormone reference intervals for babies born less than 30 weeks' gestation.

Study design

Samples were collected at 1, 4, 7, 14, 21, 28 and 42 days after birth from babies born 23–29 weeks' gestation. The serum was analyzed for seven hormones by automated chemiluminescent immunoassay (Siemens Immulite 2000). Results from the 107 infants who survived beyond 40 weeks' corrected gestational age were included in the data analysis.

Results

Cortisol, dehydroepiandrosterone sulfate, growth hormone and progesterone levels were highest during the first seven days with levels up to 10,801 nmol/L; 26.6 μmol/L; 343 mU/L; and > 63.6 nmol/L respectively. Free thyroxine levels were as low as < 2.6 pmol/L for the first 28 days with the nadir at 7 days. Estradiol levels ranged from < 73 to 1626 pmol/L over the six weeks. Reference intervals for IGF-1 could not be established as the levels were below the analyzer's sensitivity. There were no differences in reference intervals between male and female infants.

Conclusions

We describe gestation appropriate reference intervals for six hormones measured in babies born < 30 weeks' gestation. Utilization of these reference intervals permits the correct and timely interpretation of results to the clinician.     

Incomplete pediatric reference intervals for the management of patients with inborn errors of metabolism

OBJECTIVES: To evaluate the status of pediatric reference intervals for several biomarkers of inborn errors of metabolism (IEM). INTRODUCTION: There are several biomarkers that are used in many laboratories that specialize in biochemical genetics. Among them, there are acylcarnitines, total carnitine, amino acids, essential fatty acids, phytanic acid and very long chain fatty acids. These tests are key to exclusion or inclusion of an IEM, therefore appropriate age-related references intervals are crucial. A detailed review of each selected analyte is given. RESULTS: Published reference intervals do not always address the dependency of age, gender, or ethnic background; they are not established for newer laboratory methodologies and are derived from a limited number of healthy controls for most markers. CONCLUSIONS: To address the gap in pediatric reference intervals, the Canadian research project (CALIPER database) will establish comprehensive reference intervals for acylcarnitines, total carnitine, amino acids, essential fatty acids, phytanic acid, and very long chain fatty acids. All the tests will be limited to whole blood, plasma and serum samples.     

IMMULITE 2000 age and sex-specific reference intervals for alpha fetoprotein, homocysteine, insulin, insulin-like growth factor-1, insulin-like growth factor binding protein-3, C-peptide, immunoglobulin E and intact parathyroid hormone

Objectives

To determine age and sex-specific pediatric reference intervals for serum alpha fetoprotein, homocysteine, insulin, insulin-like growth factor-I, insulin-like growth factor binding protein-3, C-peptide, immunoglobulin E and parathyroid hormone.

Design and methods

The study was conducted at both Children's National Medical Center and Georgetown University, Washington D.C. Results for the above analytes were obtained from the Children's National Medical Center laboratory information system over the period of 1/5/2001-3/8/2007.Patient results using the IMMULITE 2000® were accessed and used to establish reference intervals for the analytes studied. All patient identifiers were removed except age and sex. Analysis of the data was performed at Georgetown University in the Bioanalytical Core Laboratory. The data was analyzed using the Hoffmann approach, and was computer adapted. The number of patient samples studied varied with each analyte and were: Alpha fetoprotein (557), homocysteine (924), insulin-like growth factor-1 (1352), insulin-like growth factor binding protein-3 (711), insulin (3239), C-peptide (267), immunoglobulin E (2691) and parathyroid hormone (513).

Results and conclusions

This study provides pediatric reference intervals for the eight analytes for children from birth to 18 years of age. All the analytes exhibited at least some age dependence. Sex differences between early and late childhood and adolescence were also frequently found.     

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.     

Pediatric reference values for urine particle quantification by using automated flow cytometer: Results of a multicenter study of Italian urinalysis group

Objectives

The purpose of this Italian multicenter study was to define pediatric upper reference values for urine particle quantification by using automated flow cytometry.

Design and methods

Four hospital-based clinical laboratories participated in this multicenter investigation, which included a total study population of 161 Italian children aged from 1 to 12 years. Two laboratories used Sysmex UF-100 and analyzed 86 children, whereas the other two used Sysmex UF-1000i and analyzed 75 subjects. Particle quantification included the analysis of white blood cells (WBC), red blood cells (RBC), squamous epithelial cells (EC), transitional epithelial cells (TC), casts (CAST) and bacteria (BACT).

Results

The upper reference values in subjects tested with the Sysmex UF-100 were 9.7 WBC/μL, 10.1 RBC/μL, 7.5 EC/μL, 2.5 TC/μL, 0.7 CAST/μL and 3090 BACT/μL, whereas the upper reference values in subjects tested with the Sysmex UF-1000i were 10.5 WBC/μL, 8.3 RBC/μL, 7.2 EC/μL, 2.9 TC/μL, 0.7 CAST/μL and 48 BACT/μL. No statistically significant differences between genders were found in the value distribution of any of the parameters tested. Similarly, no statistically significant differences were observed between the two urine analyzers, except for BACT.

Conclusions

Automated analysis of urine particles appears a suitable means to optimize the workflow of routine urinalysis of children specimens. The upper reference limits for pediatric subjects obtained in this study were comparable to those previously reported in the literature, with no significant differences between genders and analyzers.     

Age- and sex-specific reference values for fasting serum insulin levels and insulin resistance/sensitivity indices in healthy Iranian adults: Tehran Lipid and Glucose Study

Objectives

Increased insulin concentration is a surrogate for insulin resistance and early assessment of fasting insulin may help in identifying those who are potentially at high risk of type 2 diabetes, hypertension, and cardiovascular disease. The aim of this study was to determine age- and sex-related reference values for serum insulin and insulin resistance/sensitivity indices in Iranian subjects.

Design and methods

Serum insulin levels were measured by electrochemiluminescence immunoassay in 5786 participants of the Tehran Lipid and Glucose Study. After application of exclusion criteria, 309 non-obese healthy subjects (124 men and 185 women), aged 24–83 y, were included. The International Federation of Clinical Chemistry guidelines (non-parametric method) and the robust method were used for determining reference values.

Results

Overall 95% reference values for fasting insulin were 1.61–11.37, 2.34–11.98, and 2.11–12.49 μU/mL in men, women, and total population respectively. Mean fasting insulin concentration showed a decreasing trend with age in both genders (p for trend ≤ 0.001). Age, waist circumference, and systolic blood pressures were biological determinants of fasting insulin in both genders; in addition, insulin was modulated by triglycerides in men and fasting glucose in women. Reference intervals for HOMA1-IR, HOMA2-IR, and QUICKI were 0.63–2.68, 0.40–1.80, and 0.33–0.42, respectively.

Conclusion

This study presents the first set of reference values for fasting serum insulin to be 2–12 μU/mL for both genders in a healthy sample of Iranian adults along with the reference values for insulin resistance/sensitivity indices. These values could be used for identifying subjects with insulin resistance in epidemiological and clinical research.     

Reference intervals for whole blood viscosity using the analytical performance-evaluated scanning capillary tube viscometer

Objectives

This study was performed to establish the reference intervals for whole blood viscosity (WBV) using the analytical performance-evaluated scanning capillary tube viscometer (SCTV).

Design and methods

The analytical performance of the SCTV was evaluated using three different levels of QC materials and sixty human EDTA-blood samples. To establish the reference intervals for WBV, 297 healthy individuals (123 men and 174 women) were selected from 1083 subjects.

Results

Within-day precisions with QC materials and human whole blood and between-day precisions with QC materials were below 5.0%, 6.6% and 8.0% in CVs at all shear rates, respectively. Comparison tests between the SCTV and the Brookfield viscometer showed a significant correlation (R² = 0.972, p < 0.001). The reference intervals for WBV in healthy men were 3.66–5.41 cP at 300 s^− 1 and 23.15–36.45 cP at 1 s^− 1 while those in women were 3.27–4.32 cP at 300 s^− 1 and 18.20–27.36 cP at 1 s^− 1, respectively.

Conclusions

Using the analytical performance-evaluated SCTV, the reference intervals for WBV were established in healthy adults, which could be beneficial to the clinical utility of WBV in the aspect of appropriate modalities for the improvement of blood viscosity.     

Reference values for fasting insulin in 75 year old females and males

Objectives

Reference intervals for insulin are often based on fairly small study groups with unknown body mass index (BMI). They are also much younger than most patients seeking care. These values are not optimal for elderly patients, as many biological markers change over time and adequate reference intervals are important for correct clinical decisions.

Design and methods

We studied fasting insulin (f-insulin) values in a cohort of 698 75-year old non-diabetic males and females. The 2.5th and 97.5th percentiles for all individuals, males and females were calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference intervals.

Results

There was a strong positive correlation between BMI and f-insulin, which led to the calculation of separate reference intervals for individuals with BMI ≤ 30.

Conclusions

The reference interval for f-insulin for all study subjects was 1.74–18.27 mIU/L and for individuals with BMI ≤ 30 (n = 574) the reference interval was 1.66–15.05 mIU/L.     

Age-dependent reference intervals for measured bioavailable testosterone on the Siemens Advia Centaur: Ethnicity-specific values not necessary for South Asians

Objectives

To determine reference intervals for bioavailable testosterone for the Siemens Centaur analyzer and to assess the need for ethnicity-specific ranges for total testosterone and/or bioavailable testosterone in South Asians.

Design and methods

Testosterone was measured before and after ammonium sulphate precipitation on specimens collected from a small cohort of healthy male South Asians and Europeans.

Results

Inter-ethnicity differences in BioT and TT were not significant. Age-specific BioT reference intervals are reported.

Conclusions

Ethnicity-specific TT and BioT reference intervals for South Asians do not appear necessary.     

Clinical laboratory reference intervals in pediatrics: The CALIPER initiative

Objective and rationaleReference intervals provided on laboratory reports are essential for appropriate interpretation of test results, and can significantly impact clinical decision-making and the quality of patient care. Careful determination and/or validation of reference intervals by the laboratory for use in the patient population it serves are therefore important to ensure their proper utility. Unfortunately, critical gaps currently exist in accurate and up-to-date pediatric reference intervals for accurate interpretation of laboratory tests performed in children and adolescents. These critical gaps in the available pediatric laboratory reference intervals have the clear potential of contributing to erroneous diagnosis or misdiagnosis of many diseases of childhood and adolescence. Most of the available “normal” ranges for laboratory tests were determined over 2 decades ago on older instruments and technologies, and are no longer relevant considering the current testing technology used by clinical laboratories. It is thus critical and of utmost urgency that a more acceptable and comprehensive database be established.Discussion and conclusionIn the present review, we discuss the considerations and challenges faced when generating and validating reference intervals in accordance to the current guidelines published by the Clinical Laboratory Standards Institute (CLSI). We raise particular attention to the present-day deficiencies in available pediatric reference intervals, and highlight the special issues and unique difficulties that are additionally faced when establishing reference intervals in children. Finally, we highlight a recent Canadian initiative, the CALIPER project, whose mandate is to establish and maintain a database of comprehensive and up-to-date pediatric reference intervals to be eventually made available to all clinical laboratories worldwide.     

A systematic review of statistical methods used in constructing pediatric reference intervals

ObjectivesThis study aims to investigate current medical literature with focus on statistical methods used to construct pediatric reference intervals and identify potential gaps within the process of reference interval estimation.Design and methodsA systematic review of methods was performed. Extensive search criteria were developed and search was conducted on Embase, Medline, and PubMed databases to identify relevant articles. The articles were further screened using predefined inclusion and exclusion criteria. The selected articles were then included in our final systematic review.ResultsOur review reveals that there are gaps within current methodology and reporting of pediatric reference intervals. Not all publications followed the Clinical and Laboratory Standards Institute (CLSI) guidelines, and there is a large variation in the methods used. Discrepancies particularly arose when reference intervals were calculated for partitions with small sample sizes. In addition, the dynamic nature of pediatric data was not mostly captured when certain partitioning techniques were used.ConclusionsThere are areas within the pediatric reference interval development process that need attention. Partitioning methods particularly need to be explored with the goals of reducing subjectivity and enabling researchers to capture the best representative partitions possible. Moreover, the complicated nature of pediatric data often limits the sample size available for each partition and appropriate methods need to be considered in such cases. Researchers are also strongly encouraged to accompany their reference limits with confidence intervals to show sampling variability and demonstrate precision of their limits. These issues exemplify the need for a pediatric specific guideline that outlines a standardized way of establishing reference intervals.     

Robust features of knee osteoarthritis in joint moments are independent of reference frame selection

Background

Changes in lower-limb joint moments are important outcome measures for treatment and prevention of knee osteoarthritis. However, it is known that both the magnitude and amplitude of joint moments are affected by the choice of anatomical reference frame. The purpose of this study was to identify features of joint moment waveforms that, regardless of the choice of reference frame, are different for subjects with knee osteoarthritis as compared to asymptomatic control subjects.

Methods

External joint moments during the stance phase of gait were calculated for 44 subjects with moderate knee osteoarthritis and 44 asymptomatic subjects. Moments were then expressed using four anatomical reference frames: Joint Coordinate System, Plane of Progression, Proximal, and Distal. Principal component analysis was used to extract features of the moment waveforms that differed between control and osteoarthritis groups across all reference frames.

Findings

Principal component analysis revealed that, regardless of the choice of reference frame, subjects with knee osteoarthritis exhibited significantly decreased overall hip adduction moment magnitudes, increased overall knee adduction moment magnitudes, decreased knee internal rotation moment amplitudes, and increased early-stance ankle adduction magnitudes.

Interpretation

The four robust features identified in this study are sensitive to the effect of knee osteoarthritis, but independent of changes in the anatomical reference frame. These features can be solely attributed to the pathogenesis of the disease, and not to the artifact of reference frame selection.     

Analytical evaluation of the VITROS® 5600 Integrated System in a pediatric setting and determination of pediatric reference intervals

ObjectivesTo evaluate the VITROS^® 5600 Integrated System in a pediatric setting and to determine age- and gender-specific pediatric reference intervals for several common analytes.Design and methodsThe instrument was evaluated using QC material and patient samples. Reference intervals were determined using samples obtained from children attending select outpatient clinics.ResultsImprecision analysis for 25 analytes and serum indices, the turnaround time for a simulated workload, and MicroSensor performance were assessed in our pediatric laboratory. Pediatric reference intervals for 25 analytes were also determined according to the CLSI/IFCC C28-A3 guidelines using 770 samples and over 15,000 analyses.ConclusionThe VITROS 5600 Integrated System is suitable for use in a pediatric setting. Age- and gender-partitioned pediatric reference intervals for 25 common analytes were also determined as a pilot to the ongoing CALIPER project. These reference intervals are valuable for all VITROS^® users as well as any laboratory assessing these analytes once they demonstrate the acceptability of transference to their laboratory.