Reference intervals for serum cystatin C in neonates and children 30 days to 18 years old.

BACKGROUND: Serum cystatin C (CysC) is a promising biomarker of kidney function, which has higher accuracy and sensitivity when compared with creatinine. To better utilize serum CysC in clinical practice, this study aimed to establish continuous paediatric reference intervals (RIs) for serum CysC. METHODS: The study subjects consisted of healthy term neonates and children aged 30 days to 18 years. Venous blood samples were collected and serum CysC levels were measured using the immunoturbidimetric measurement principle. Fractional polynomial regression model and quantile regression was applied in the statistical analysis to generate continuous RIs. RESULTS: A total of 378 samples with equal numbers of males and females were analysed for serum CysC. No outliers were found in this analysis. The continuous RIs are presented as equations and graphical scatterplots. CONCLUSIONS: This study established continuous paediatric reference intervals (RIs) for serum CysC in healthy term neonates and children. The continuous RIs generated from this study show age-based dynamic changes as well as blood group and gender-specific differences for serum CysC. Graphical abstract.

Reference Values for 30 Common Biochemistry Analytes Across 5 Different Analyzers in Neonates and Children 30 Days to 18 Years of Age.

BACKGROUND: Age-specific reference intervals (RIs) have been developed for biochemistry analytes in children. However, the ability to interpret results from multiple laboratories for 1 individual is limited. This study reports a head-to-head comparison of reference values and age-specific RIs for 30 biochemistry analytes for children across 5 analyzer types. METHODS: Blood was collected from healthy newborns and children 30 days to <18 years of age. Serum aliquots from the same individual were analyzed on 5 analyzer types. Differences in the mean reference values of the analytes by the analyzer types were investigated using mixed-effect regression analysis and by comparing maximum variation between analyzers with analyte-specific allowable total error reported in the Westgard QC database. Quantile regression was used to estimate age-specific RIs using power variables in age selected by fractional polynomial regression for the mean, with modification by sex when appropriate. RESULTS: The variations of age-specific mean reference values between analyzer types were within allowable total error (Westgard QC) for most analytes, and common age-specific reference limits were reported as functions of age and/or sex. Analyzer-specific reference limits for all analytes on 5 analyzer types are also reported as functions of age and/or sex. CONCLUSIONS: This study provides quantitative and qualitative measures of the extent to which results for individual children can or cannot be compared across analyzer types, and the feasibility of RI harmonization. The reported equations enable incorporation of age-specific RIs into laboratory information systems for improving evidence-based clinical decisions in children.

Validation of the HAPPI Kids Continuous Age-Specific Pediatric Reference Intervals.

INTRODUCTION: To facilitate best possible patient care, reference intervals (RIs) adopted by a laboratory must be appropriate for the population demographics and, where applicable, the analytical principle and/or the analytical instrument used. While guidelines from the Clinical and Laboratory Standard Institute (CLSI) recommend a validation process for discrete RIs, there are no current recommendations for the validation process for continuous RIs. This study aimed to validate recently published, HAPPI Kids continuous RIs, in a routine laboratory. METHODS: Initially, the difference in test results between the primary study laboratory that contributed to previous RIs development and a routine laboratory was assessed using specimens from 77 children tested in both laboratories using the Siemens ADVIA 1800 or Centaur/XP/XPT. Later, validation of the HAPPI Kids RIs was undertaken using 279 pediatric samples tested on the same analyzer type in the routine laboratory. The previously published RIs were validated if more than 90% of results in the routine laboratory were within the RIs. RESULTS: There was minimal evidence of clinically significant differences in test results between the primary and routine laboratories. The continuous RIs were validated after initial analysis for 16 of the 18 biochemistry analytes tested, and after secondary analysis for the remaining 2 analytes. CONCLUSION: This study validates the HAPPI Kids RIs in a routine laboratory, satisfying the laboratory accreditation requirements for evaluation, implementation, and sourcing of RIs. In addition, this study presents a modification of the current CLSI method for validation of continuous RIs that will benefit routine laboratories in general.

Point-of-care monitoring of oral anticoagulation therapy in children. Comparison of the CoaguChek XS system with venous INR and venous INR using an International Reference Thromboplastin preparation (rTF/95).

Point-of-care (POC) monitoring of oral anticoagulation has been widely adopted in both paediatric and adult patients. A new POC system, the CoaguChek XS has recently been developed to measure the international normalised ratio (INR) and may offer significant advantages. The CoaguChek XS utilises a new method of electrochemical clot detection based on thrombin generation. This system has not been previously evaluated in children with reference to the laboratory gold standard, the prothrombin time using reference thromboplastin. It was the objective to compare values obtained by the CoaguChek XS system with both the venous INR and the gold standard for anticoagulant monitoring, prothrombin time with reference thromboplastin (rTF/95). To evaluate the impact of testing using the CoaguChek XS on clinical anticoagulant dosing decisions. Fifty paired venous INR and capillary CoaguChek XS results were obtained from 31 children (aged up to 16 years). The laboratory gold standard, a manual prothrombin time with reference thromboplastin (rTF/95) was additionally performed on 26 samples. Correlation between the CoaguChek XS result and the venous INR was r = 0.810. Agreement between the CoaguChek XS result and the reference INR was shown to be higher (r=0.95), in the subset analysed by this method. Correlation between the venous INR and reference INR was r=0.90. Despite changes to the methodology of testing with the CoaguChek XS POC monitoring system, the accuracy of this method when compared with both the venous INR and gold standard reference INR was satisfactory. This resulted in infrequent changes to clinical decision making regarding anticoagulation.

A prospective, cross-sectional study to establish age-specific reference intervals for neonates and children in the setting of clinical biochemistry, immunology and haematology: the HAPPI Kids study protocol.

INTRODUCTION: The clinical interpretation of laboratory tests is reliant on reference intervals. However, the accuracy of a reference interval is dependent on the selected reference population, and in paediatrics, the ability of the reference interval to reflect changes associated with growth and age, as well as sex and ethnicity. Differences in reagent formulations, methodologies and analysers can also impact on a reference interval. To date, no direct comparison of reference intervals for common analytes using different analysers in children has been published. The Harmonising Age Pathology Parameters in Kids (HAPPI Kids) study aims to establish age-appropriate reference intervals for commonly used analytes in the routine clinical care of neonates and children, and to determine the feasibility of paediatric reference interval harmonisation by comparing age-appropriate reference intervals in different analysers for multiple analytes. METHODS AND ANALYSIS: The HAPPI Kids study is a prospective cross-sectional study, collecting paediatric blood samples for analysis of commonly requested biochemical, immunological and haematological tests. Venous blood samples are collected from healthy premature neonates (32-36 weeks of gestation), term neonates (from birth to a maximum of 72 hours postbirth) and children aged 30 days to ≤18 years (undergoing minor day surgical procedures). Blood samples are processed according to standard laboratory procedures and, if not processed immediately, stored at -80°C. A minimum of 20 samples is analysed for every analyte for neonates and then each year of age until 18 years. Analytical testing is performed according to the standard operating procedures used for clinical samples. Where possible, sample aliquots from the same patients are analysed for an analyte across multiple commercially available analysers. ETHICS AND DISSEMINATION: The study protocol was approved by The Royal Children's Hospital, Melbourne, Ethics in Human Research Committee (34183 A). The study findings will be published in peer-reviewed journals and shared with clinicians, laboratory scientists and laboratories.

Effective role redesign: an audit of outcomes following the introduction of a new nurse-led service.

Genitourinary medicine services have had to modernize to try to meet the growth in demand. Changes should be audited to ensure standards remain high. We introduced a 'comprehensive care nurse-led service' for patients presenting for asymptomatic screening and as asymptomatic contacts (partners of known positive patients). Following implementation we audited outcomes and patient satisfaction. During the audit period (01/07/2005 to 30/11/2005), 446 patients were seen. A sexual health screen was performed in 433 (216 females: 217 males). Forty-one patients (9.5%) were chlamydia-positive by enzyme-linked immunosorbent assay testing (background clinic rate 8.5%). Forty-six (10.6%) were treated epidemiologically as chlamydia-negative contacts of chlamydia-positive index patients and 18 (4.1%) were treated as chlamydia-negative urethritis/cervicitis. Uptake of HIV testing was 71.2% (311/433). Average wait-to-appointment was three days (background clinic wait 2-3 weeks). Nurse-led clinics were judged successful in terms of outcomes, improving access and patient satisfaction.

Point of care monitoring of oral anticoagulant therapy in children: comparison of CoaguChek Plus and Thrombotest methods with venous international normalised ratio.

This paper reports the outcome of a research protocol aimed at optimising warfarin monitoring in a tertiary pediatric centre. The Thrombotest INR was the standard monitoring test employed to manage oral anticoagulant therapy in children at the Royal Children's Hospital (RCH), Melbourne. This study compares the results of this standard method to the novel CoaguChek INR monitor and the "gold standard" technique of venous INR sampling. The objectives were to determine 1) if point-of-care techniques of measuring the INR (Thrombotest and CoaguChek) are accurate and reliable compared to INR results obtained from venous sampling, processed in an accredited laboratory, and 2) if INR results generated by POC devices can be safely used to manage oral anticoagulant therapy in children. 18 children (10 females and 8 males) participated in the study. Ages ranged from 9 months to 21 years (Mean 11.9 years; SD 5.03 years). The agreement between CoaguChek and venous INR measurements (r = 0.885) was shown to be higher compared to Thrombotest and venous INR (r = 0.700). Compared to the venous INR, values obtained with Coaguchek and Thrombotest crossed into or out of the therapeutic range in 25% and 36% of cases respectively. In 88% of the CoaguChek cases and 57% Thrombotest cases, the difference from the venous result was less than 0.5. The CoaguChek method of INR monitoring is a more accurate and reliable method compared to Thrombotest, in the pediatric population tested, and can be safely used to manage oral anticoagulant therapy in children.