A Parametric Empirical Bayes Approach to Personalized Reference Intervals and Reference Change Values.

Background: Population-wide reference intervals (RIpop) are commonly used in laboratory medicine but may not reflect an individual's tightly regulated homeostatic interval. Personalized reference intervals (RIper) could enhance diagnostic precision by accounting for individual variability. A parametric empirical Bayes (PEB) framework stabilizes individual estimates using population parameters, enabling reliable RIper even from a limited number of individual results.

Cardiometabolic Biomarkers and Prediction of Kidney Disease Progression: The eGFR Cohort Study.

Background: Traditional markers modestly predict chronic kidney disease progression in Aboriginal and Torres Strait Islander people. Therefore, we assessed associations of cardiometabolic and inflammatory clinical biomarkers with kidney disease progression among Aboriginal and Torres Strait Islander people with and without diabetes.

Objectives: To identify cardiometabolic and inflammatory clinical biomarkers that predict kidney disease progression in Aboriginal and Torres Strait Islander people.

Aligning kidney function assessment in patients with cancer to global practices in internal medicine.

Unlabelled: The kidney disease: Improving Global Outcomes (KDIGO) guideline recommends assessing kidney function using glomerular filtration rate (GFR) either through direct measurement or through estimation (eGFR) and describes a standardised classification of reduced kidney function. KDIGO guidelines have been adopted by most internal medicine specialities for the assessment and classification of kidney function, but not by cancer medicine. The development of the International Consensus Guideline on Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) aims to overcome the perceived challenges with KDIGO recommendations by describing their utility in patients with cancer.

Estimating Reference Change Values Using Routine Patient Data: A Novel Pathology Database Approach.

Background: The reference change value (RCV) is calculated by combining the within-subject biological variation (CVI) and local analytical variation (CVA). These calculations do not account for the variation seen in preanalytical conditions in routine practice or CVI in patients presenting for treatment. As a result, the RCVs may not reflect routine practice or align with clinicians' experiences.

Outcome-based analytical performance specifications: current status and future challenges.

Analytical performance specifications (APS) based on outcomes refer to how 'good' the analytical performance of a test needs to be to do more good than harm to the patient. Analytical performance of a measurand affects its clinical performance. Without first setting clinical performance requirements, it is difficult to define how good analytically the test needs to be to meet medical needs.

Applying the Milan models to setting analytical performance specifications - considering all the information.

Analytical performance specifications (APS) are used for decisions about the required analytical quality of pathology tests to meet clinical needs. The Milan models, based on clinical outcome, biological variation, or state of the art, were developed to provide a framework for setting APS. An approach has been proposed to assign each measurand to one of the models based on a defined clinical use, physiological control, or an absence of quality information about these factors.

A New Concept for Reference Change Values-Regression to the Population Mean.

Background: Reference change values (RCV) are used to indicate a change in analyte concentration that is unlikely to be due to random variation in the patient or the measurement. Current theory describes RCV relative to a first measurement result (X1). We investigate an alternative view predicting the starting point for RCV calculations from X1 and its location in the reference interval.

Using analytical performance specifications in a medical laboratory.

Analytical performance specifications (APS) are used for the quantitative assessment of assay analytical performance, with the aim of providing information appropriate for clinical care of patients. One of the major locations where APS are used is in the routine clinical laboratory. These may be used to assess and monitor assays in a range of settings including method selection, method verification or validation, external quality assurance, internal quality control and assessment of measurement uncertainty.

Sharing reference intervals and monitoring patients across laboratories - findings from a likely commutable external quality assurance program.

Objectives: Laboratory results are increasingly interpreted against common reference intervals (CRIs), published clinical decision limits, or previous results for the same patient performed at different laboratories. However, there are no established systems to determine whether current analytical performance justifies these interpretations. We analysed data from a likely commutable external quality assurance program (EQA) to assess these interpretations.

Total bilirubin assay differences may cause inconsistent treatment decisions in neonatal hyperbilirubinaemia.

Objectives: To assess interlaboratory variability of total serum bilirubin (TSB) results in newborns. Initiated following a clinical incident in which a neonate was transferred to a tertiary hospital for treatment of severe hyperbilirubinemia but on arrival was reclassified into a lower risk category due to a 20% difference in TSB between laboratories.

Methods: Fresh residual plasma samples from hospital-born infants were pooled to obtain 11 samples across a range of total bilirubin concentrations.

The effect of acute changes in glomerular filtration rate on common biochemical tests.

Objectives: To characterise the effect of acute kidney injury on the concentration of common biochemical analytes.

Design: and methods: Pairs of serum or plasma samples from the same patients routinely submitted to the laboratory were subject to further analysis based on changes in serum creatinine within 72 h. Samples collected from patients on dialysis were excluded.

Metrological traceability and clinical traceability of laboratory results - the role of commutability in External Quality Assurance.

The role of an External Quality Assurance (EQA) program is generally seen as providing a service to routine laboratories that their analytical performance is satisfactory and stimulating corrective action in the event of poor results. It is recognised that an ideal EQA program uses materials that are commutable with patient samples and have values assigned by higher-order reference methods. Despite this, most routine EQA programs use materials without verified commutability and use consensus means (based on either peer group or all laboratories) as target values.

Variability in insulin pharmacokinetics following high-dose insulin therapy.

Introduction: High dose insulin (HDI) therapy for cardiogenic shock from acute poisoning can be complicated by treatable hypoglycemia which persists following poisoning recovery. Glucose requirements post-HDI reflect supraphysiological insulin plasma concentration. A publication reported a patient treated with HDI with plasma insulin concentrations >1000 µU/mL and elimination half-life 10-18 h requiring intravenous glucose replacement for >5 days.

AACC Guidance Document on Laboratory Investigation of Acute Kidney Injury.

Background: Acute kidney injury (AKI) is a sudden episode of kidney damage or failure affecting up to 15% of hospitalized patients and is associated with serious short- and long-term complications, mortality, and health care costs. Current practices to diagnose and stage AKI are variable and do not factor in our improved understanding of the biological and analytical variability of creatinine. In addition, the emergence of biomarkers, for example, cystatin C, insulin-like growth factor binding protein 7, and tissue inhibitor of metalloproteinases 2, and electronic notification tools for earlier detection of AKI, highlights the need for updated recommendations to address these developments.

Thyroid Peroxidase Antibody Positivity is Associated With Relapse-Free Survival Following Antithyroid Drug Treatment for Graves Disease.

Objective: Graves' disease is an autoimmune disease characterized by production of autoantibodies directed against the thyroid gland. Thyrotropin-receptor antibodies (TRAbs) are clearly pathogenic, but the role of thyroidperoxidase antibodies (TPOAbs) in Graves disease is unknown.

Methods: We retrospectively studied whether TPOAb positivity reduced risk of relapse following antithyroid drug (ATD) treatment in newly diagnosed Graves disease.

Effects of Allopurinol on the Progression of Chronic Kidney Disease.

Background: Elevated serum urate levels are associated with progression of chronic kidney disease. Whether urate-lowering treatment with allopurinol can attenuate the decline of the estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease who are at risk for progression is not known.

Methods: In this randomized, controlled trial, we randomly assigned adults with stage 3 or 4 chronic kidney disease and no history of gout who had a urinary albumin:creatinine ratio of 265 or higher (with albumin measured in milligrams and creatinine in grams) or an eGFR decrease of at least 3.

Is hyperfiltration associated with higher urine albumin-to-creatinine ratio at follow up among Indigenous Australians? The eGFR follow-up study.

Background: Glomerular hyperfiltration is not able to be detected in clinical practice. We assessed whether hyperfiltration is associated with albuminuria progression among Indigenous Australians at high risk of diabetes and kidney disease to determine its role in kidney disease progression.

Methods: Longitudinal observational study of Indigenous Australians aged ≥18 years recruited from >20 sites, across diabetes and/or kidney function strata.

Estimates of Within-Subject Biological Variation Derived from Pathology Databases: An Approach to Allow Assessment of the Effects of Age, Sex, Time between Sample Collections, and Analyte Concentration on Reference Change Values.

Background: Within-subject biological variation data (CV) are used to establish quality requirements for assays and allow calculation of the reference change value (RCV) for quantitative clinical laboratory tests. The CV is generally determined using a large number of samples from a small number of individuals under controlled conditions. The approach presented here is to use a small number of samples (n = 2) that have been collected for routine clinical purposes from a large number of individuals.

An evaluation of risk factors to predict target concentration non-attainment in critically ill patients prior to empiric β-lactam therapy.

To determine whether target concentration non-attainment can be anticipated in critically ill patients prior to initiating empiric β-lactam antibiotic therapy based on readily available clinical factors. Retrospective review of consecutive patients treated with piperacillin or meropenem and who underwent therapeutic drug monitoring (TDM) at St Vincent's Hospital (Sydney, Australia) between January 2013 and December 2015 was performed. Predefined subgroups were patients who received continuous renal replacement therapy (CRRT) and those who did not (non-CRRT).

Indirect methods for reference interval determination - review and recommendations.

Reference intervals are a vital part of the information supplied by clinical laboratories to support interpretation of numerical pathology results such as are produced in clinical chemistry and hematology laboratories. The traditional method for establishing reference intervals, known as the direct approach, is based on collecting samples from members of a preselected reference population, making the measurements and then determining the intervals. An alternative approach is to perform analysis of results generated as part of routine pathology testing and using appropriate statistical techniques to determine reference intervals.