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The Australasian Association of Clinical Biochemists (AACB) has over the past 5 years been actively working to achieve harmonized reference intervals (RIs) for common clinical chemistry analytes using an evidence-based checklist approach where there is sound calibration and metrological traceability. It has now recommended harmonized RIs for 18 common clinical chemistry analytes which are performed in most routine laboratories and these have been endorsed by the Royal College of Pathologists of Australasia (RCPA). In 2017 another group of analytes including urea, albumin and arterial blood gas parameters were considered and suggested harmonized RIs proposed. This report provides an update of those harmonization efforts. [ABSTRACT FROM AUTHOR]

Reference Intervals (RIs) and clinical decision limits (CDLs) are a vital part of the information supplied by laboratories to support the interpretation of numerical clinical pathology results. RIs describe the typical distribution of results seen in a healthy reference population while CDLs are associated with a significantly higher risk of adverse clinical outcomes or are diagnostic for the presence of a specific disease. However, as the two concepts are sometimes confused, there is a need to clarify the differences between these terms and to ensure they are easily distinguished, especially because CDLs have a clinical association with specific diseases and risks, thereby implying that effective clinical interventions are available. It is important to note that, because population-based RIs are derived from the range of values expected in a typical community population, laboratory results that fall outside a RI do not necessarily indicate a disease but rather that additional medical follow-up and/or treatment may be warranted. In contrast, CDLs are associated with a risk of specific adverse outcomes, and are commonly used to interpret laboratory test results, including lipid parameters, glucose, hemoglobin A1c (HbA1c), and tumor markers, to determine risk of disease, to diagnose or to treat. In recent years, the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Committee on Reference Intervals and Decision Limits (C-RIDL) has focused primarily on RIs and has performed multicenter studies to obtain common RIs. However, the broader responsibility of the Committee, from its name, includes “decision limits”. C-RIDL now aims to emphasize the importance of the correct use of both RIs and CDLs and to encourage laboratories to specify the appropriate information to clinicians as needed. This review discusses RIs and CDLs in detail, describes the similarities and the differences between these two important tools in laboratory medicine, and clearly explains the processes used to define them. C-RIDL encourages the involvement of laboratory professionals in the establishment of both RIs and CDLs. [ABSTRACT FROM AUTHOR]

Background: Age-specific trends of serum testosterone and sex hormone-binding globulin across the full lifespan have not been reported.Methods: We deduced age-specific trends in serum testosterone and sex hormone-binding globulin in males and females between ages 10 and 90 from a large sample of consecutive results from a single large pathology laboratory. Coded results of 110,712 consecutive blood samples requesting serum testosterone over seven years (2007-2013) comprising blood testosterone, sex hormone-binding globulin and calculated free testosterone together with gender and age were analysed create smoothed age-specific centiles (2.5%, 5%, 25%, 50%, 75%, 95%, 97.5%) for males and females.Results: These identified the pubertal increases in serum testosterone in males peaking at 20 years of age and remaining stable thereafter until the eighth decade. In females, circulating testosterone peaked in late adolescence and declined gradually over the next two decades but remained stable across menopause and beyond. After early childhood, serum sex hormone-binding globulin declines to a nadir in males at the age of 20 years and remains stable till the sixth decade with a gradual, progressive rise thereafter. In females, the sex hormone-binding globulin nadir is reached earlier with levels rising gradually and progressively with age thereafter and accelerating after the age of 70 years. Females also exhibit a second sex hormone-binding globulin peak during reproductive ages reflected only in upper centiles due to effects of pregnancy and oral contraceptive use in a significant minority of females.Conclusions: This large sample of clinical data provides a comprehensive profile of androgen status across the lifespan from early adolescence to late old age. [ABSTRACT FROM AUTHOR]

The authors discuss changes in maternal physiology which cause changes in electrolyte and acid-base status of pregnant women and the factors to consider in adopting pregnancy-specific reference intervals. Topics discussed include the role of pregnancy reference intervals in clinical biochemistry, pregnancy dating and defining partitions, and vascular and renal physiology changes during pregnancy. It also discusses analytes such as sodium, potassium and chloride.

Abstract: Although we are in the era of evidence-based medicine, there is still a substantial gap between theory and current practice with the application of reference intervals as decision making tools. Different laboratories may have different reference intervals for the same tests using the same analytical methods and platforms. These differences have the potential to confuse physicians making the assessment and monitoring of patients more difficult by providing discordant information. This paper attempts to demonstrate how to use evidence-based approach for harmonising reference intervals. In order to consider harmonisation we must first have an appreciation of the various factors that influence the determination of that reference interval such as the choice of individuals within the population studied, biological variability of the analyte studied, partitioning, sample collection, analytical aspects such as bias and statistical models. An a priori approach for determining reference intervals, whilst recommended, may be beyond the scope of most laboratories and consideration should be given to the use of a validated indirect a posteriori approach. Regardless of method used, the continuing application of an evidence-based approach in harmonised reference intervals to meet the quality expectations of physicians should be pursued. [Copyright &y& Elsevier]

The concentration of prostate specific antigen in the blood can help in the assessment and management of early prostate cancer. However, it is important to understand the biology underlying the test. recent refinements have addressed some of the weaknesses of the test. These include age-related prostate specific antigen reference limits, the free to total prostate specific antigen ratio and prostate specific antigen rates of change including velocity or doubling time. Measuring prostate specific antigen without understanding the underlying biology or without applying these refinements may result in more harm than good. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "More on Biotin Treatment Mimicking Graves' Disease" by Sebastian Kummer and colleagues that was published in the August 18, 2016 issue; and also presents a response from the author of the same.

Objective: To compare the performance of two anti‐Mullerian (AMH) assays over a range of concentrations, in samples collected from young women. Design: A cross‐sectional method‐comparison study of 168 non‐healthcare‐seeking women. Participants: Included women were aged 18–39 years, not recently pregnant, breast feeding or using systemic hormones. Measurements: Serum AMH levels were analysed with the Beckman Coulter Access 2 assay from fresh samples and the Ansh picoAMH assay using samples stored at −80°C, in a parallel setting. Comparisons between the two assays were examined using Bland‐Altman plots. Results: Participants had a mean ± SD age of 32.6 ± 5.4 years and body mass index of 28.1 ± 7.9 kg/m2, and 60.1% were parous. Although the assay results were highly correlated (Spearman correlation.982, P <.001), the relationship between the assays was nonlinear. Serum AMH values below 4 pmol/L were lower with the picoAMH assay compared with the Access AMH assay (mean difference in this range was −0.49 pmol/L), but for samples with a mean value above 10 pmol/L, the picoAMH assay consistently measured higher than the Access AMH assay (mean difference in this range was +8.2 pmol/L). As AMH concentrations increased the absolute discrepancy between the assays also increased. Conclusions: This study demonstrates that despite the high correlation between two commercially available AMH assays, the assays performed in a discordant manner at high and low concentrations. Hence, the results of these assays are not interchangeable, highlighting the need to establish specific reference limits for individual assays to guide clinical decision‐making and the challenge of establishing future universal cut‐offs for the application of AMH levels in clinical practice. [ABSTRACT FROM AUTHOR]

Reference intervals are established either by direct or indirect approaches. Whereas the definition of direct is well established, the definition of indirect is still a matter of debate. In this paper, a general definition that covers all indirect models presently in use is proposed. With the upcoming popularity of indirect models, it has become evident that further partitioning strategies are required to minimize the risk of patients' false classifications. With indirect methods, such partitions are much easier to execute than with direct methods. The authors believe that the future of reference interval estimation belongs to indirect models with big data pools either from one laboratory or combined from several regional centres (if necessary). Independent of the approach applied, the quality assurance of the pre-analytical and analytical phase, considering biological variables and other confounding factors, is essential. [ABSTRACT FROM AUTHOR]

The natriuretic hormones have been discovered as mediators of the cardiac response to volume overload and mechanical dysfunction. Although there are some physiological differences between atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), it is BNP that has been found to be most useful as a clinical test. BNP is secreted along with an N terminal proBNP cleavage product (NT-proBNP). The similarities between these two tests are far greater than the differences. They are both probably useful in the diagnosis of high-risk patients (e.g. dyspnoeic) and may be useful in monitoring cardiac failure treatment. Although BNP levels in the normal range predict the risk of cardiac events and mortality, there is little evidence to promote their use as a screening test. In such an important condition as cardiac failure we should consider any messages that are likely to be of value, particularly those that are heartfelt. [Copyright &y& Elsevier]

The article presents information on a study aimed at establishing reference intervals (RIs) for thyroid stimulating hormone (TSH), free thyroxine (fT4). It also aimed to track intraindividual changes in thyroid function during pregnancy in 130 women without antithyroid peroxidase antibodies. It has been concluded that the use of trimester-specific RIs would prevent thyroid function misclassification during pregnancy.

The article reports a study which was conducted to determine the incidence and risk factors for exercise-associated hyponatremia (EAH) in cyclists completing a long-distance bike ride and whether it is associated with Higher NT-proBNP concentration (brain natriuretic protein precursor). EAH was found to occur in 4.5 percent cyclists after 10 hours of cycling, these riders gained body weight during the ride and reported greater fluid intake. Three riders had significant elevations of NT-proBNP.

Background: Serum free testosterone (FT) concentrations are commonly requested, but because reference FT methods are too laborious various calculational algorithms for FT based on total testosterone (TT) and sex hormone-binding globulin (SHBG) are frequently used. This study provides the first large-scale evaluation of the predictive accuracy and sources of variability for different FT formulae compared with direct laboratory measurements. Methods: Using a large data-set of direct FT measurements by centrifugal ultrafiltration, the predictive accuracy of five different formulas for cFT (four existing plus a new formula) is evaluated in 3975 consecutive blood samples. In a second dataset of 124 samples from a reference panel of healthy eugonadal young men, we estimate the relative influence of the five algorithms and eight different TT and two SHBG assays including all available commercial total TT and SHBG assays together with a gas chromatography/mass spectrometry T reference method. Results: cFT formulae show wide discrepancies with equilibrium-binding algorithms showing systematic overestimation relative to direct FT measurements, whereas two empirical cFT methods were more concordant. Variations between commercially available TT immunoassays have a strong impact on calculation of FT with TT assays contributing 82.2% of overall variance compared with 13.7% for the cFT algorithms and 4.1% for the SHBG assays. Conclusions: If FT measurements are requested and direct measurement impractical, cFT formulae using TT and SHBG immunoassays provide an approximation to direct FT measurement that is strongly dependent on the TT, cFT formula used and, to a lesser extent, SHBG immunoassays. [ABSTRACT FROM AUTHOR]

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. This is known as the indirect approach. This paper from a working group of the International Federation of Clinical Chemistry (IFCC) Committee on Reference Intervals and Decision Limits (C-RIDL) aims to summarize current thinking on indirect approaches to reference intervals. The indirect approach has some major potential advantages compared with direct methods. The processes are faster, cheaper and do not involve patient inconvenience, discomfort or the risks associated with generating new patient health information. Indirect methods also use the same preanalytical and analytical techniques used for patient management and can provide very large numbers for assessment. Limitations to the indirect methods include possible effects of diseased subpopulations on the derived interval. The IFCC C-RIDL aims to encourage the use of indirect methods to establish and verify reference intervals, to promote publication of such intervals with clear explanation of the process used and also to support the development of improved statistical techniques for these studies. [ABSTRACT FROM AUTHOR]

Objective: Gestational Diabetes Mellitus (GDM) increases the risk of type 2 diabetes. A register can be used to follow-up high risk women for early intervention to prevent progression to type 2 diabetes. We evaluate the performance of the world’s first national gestational diabetes register. Research design and methods: Observational study that used data linkage to merge: (1) pathology data from the Australian states of Victoria (VIC) and South Australia (SA); (2) birth records from the Consultative Council on Obstetric and Paediatric Mortality and Morbidity (CCOPMM, VIC) and the South Australian Perinatal Statistics Collection (SAPSC, SA); (3) GDM and type 2 diabetes register data from the National Gestational Diabetes Register (NGDR). All pregnancies registered on CCOPMM and SAPSC for 2012 and 2013 were included–other data back to 2008 were used to support the analyses. Rates of screening for GDM, rates of registration on the NGDR, and rates of follow-up laboratory screening for type 2 diabetes are reported. Results: Estimated GDM screening rates were 86% in SA and 97% in VIC. Rates of registration on the NGDR ranged from 73% in SA (2013) to 91% in VIC (2013). During the study period rates of screening at six weeks postpartum ranged from 43% in SA (2012) to 58% in VIC (2013). There was little evidence of recall letters resulting in screening 12 months follow-up. Conclusions: GDM Screening and NGDR registration was effective in Australia. Recall by mail-out to young mothers and their GP’s for type 2 diabetes follow-up testing proved ineffective. [ABSTRACT FROM AUTHOR]

Background Biotin interference in streptavidin-based immunoassays causes widespread analytical distortions that may lead to clinical confusion, inappropriate patient management and, ultimately, adverse events. Its prevalence has increased recently due to the increased use of high-dose biotin therapy in specific patient groups (notably multiple sclerosis) and possibly the general community. Methods We have developed a method to deplete biotin from samples using the streptavidin-coated magnetic microparticles that are a component of most susceptible assays. Results We show that high concentrations of spiked biotin can be adequately depleted from serum using this approach, and that gross biochemical derangements can be restored to normality. We also show that biotin in samples derived from multiple sclerosis patients receiving 300 mg biotin daily can be adequately depleted to remove associated analytical interference and restore normal results. The method is applicable to competitive and sandwich immunoassays and importantly, because it does not change the volume of the sample, suitable for the measurement of free thyroid hormone assays. Application of the method does not significantly change the precision of measurement, and for the majority of analytes, the accuracy is not substantially altered. Conclusions Adopting this method enables laboratories to confirm biotin interference in the appropriate clinical setting. Moreover, it enables laboratories to remove the interference and report accurate and reliable results, without the need for patients to withhold beneficial therapy prior to blood tests. Until the biotin tolerance of susceptible assays is improved, our method gives laboratories a safe alternative for reporting results using streptavidin-based methods. [ABSTRACT FROM AUTHOR]

Background Biotin interference is a significant problem to which at-risk laboratories must now be attuned. We sought to systematically characterize the nature of this interference in Roche immunoassays. Methods Known concentrations of biotin were titrated into serum samples and the effects on competitive and sandwich immunoassays were analysed. The maximum and minimum concentrations examined reflect those likely to be achieved in individuals on 5 to 10 mg supplements at the lower end, and 100 to 300 mg biotin at the high end. Results A high variability in biotin tolerance was observed. Some assays, such as troponin T, TSH and antithyroid antibodies, were extremely sensitive to the lower concentrations of biotin (15.6 and 31.3 ng/mL), whereas the majority of assays were relatively resistant. At concentrations ≥500 ng/mL, all assays showed significant interference from biotin but, again, the magnitude of the interference was variable. The more sensitive assays showed profound analytical bias at biotin concentrations that occur with high-dose therapy. Conclusion Our data demonstrate high variability in biotin tolerance across Roche immunoassays. The shape of the dose-response curves provides more detailed information than the single manufacturer-quoted figure for biotin tolerance. Accordingly, these data may be used by laboratories for more accurate risk assessment in predicting the effects of biotin. Our data may also be extrapolated to guide timing of blood tests in patients on high-dose biotin therapy: it demonstrates the number of half-lives required to withhold biotin in order to decrease its concentration to below a given assay tolerance. [ABSTRACT FROM AUTHOR]

Background: The determination of reliable, practical Quality Indicators (QIs) from presentation of the patient with a pathology request form through to the clinician receiving the report (the Total Testing Process or TTP) is a key step in identifying areas where improvement is necessary in laboratories. Methods: The Australasian QIs programme Key Incident Monitoring and Management System (KIMMS) began in 2008. It records incidents (process defects) and episodes (occasions at which incidents may occur) to calculate incident rates. KIMMS also uses the Failure Mode Effects Analysis (FMEA) to assign quantified risk to each incident type. The system defines risk as incident frequency multiplied by both a harm rating (on a 1-10 scale) and detection difficulty score (also a 1-10 scale). Results: Between 2008 and 2016, laboratories participating rose from 22 to 69. Episodes rose from 13.2 to 43.4 million; incidents rose from 114,082 to 756,432. We attribute the rise in incident rate from 0.86% to 1.75% to increased monitoring. Haemolysis shows the highest incidence (22.6% of total incidents) and the highest risk (26.68% of total risk). "Sample is suspected to be from the wrong patient" has the second lowest frequency, but receives the highest harm rating (10/10) and detection difficulty score (10/10), so it is calculated to be the 8th highest risk (2.92%). Similarly, retracted (incorrect) reports QI has the 10th highest frequency (3.9%) but the harm/difficulty calculation confers the second highest risk (11.17%). Conclusions: TTP incident rates are generally low (less than 2% of observed episodes), however, incident risks, their frequencies multiplied by both ratings of harm and discovery difficulty scores, concentrate improvement attention and resources on the monitored incident types most important to manage. [ABSTRACT FROM AUTHOR]

It is unknown if high prolactin levels during pregnancy contribute to the development of gestational diabetes. We hypothesized that higher prolactin levels are associated with reduced glucose tolerance, as determined by higher 2-h glucose level from an oral glucose tolerance test in pregnancy. The 75-g oral glucose tolerance test was carried out at 28 weeks of gestation in 69 participants. A multiple regression analysis was used to determine the relationship between serum prolactin and 2-h glucose levels. Multivariable regression analysis showed an independent and significant relationship between third trimester prolactin and 2-h glucose levels post oral glucose tolerance test. Higher prolactin levels were associated with higher glucose levels independent of age, body mass index, gravidity and parity. Higher prolactin levels associated with reduced glucose tolerance in the third trimester of pregnancy suggests the possible independent role of prolactin in the pathogenesis of gestational diabetes. [ABSTRACT FROM AUTHOR]

Aims Uncertainties about the role of cystatin C-based estimated glomerular filtration rate (eGFR) in the prediction of cardiovascular disease (CVD) beyond traditional CVD risk factors remain. We assessed contributions of eGFR to CVD and mortality in the general population. Methods Using 14 year follow-up data on 9353 adults without a reported history of CVD from the Australian Diabetes, Obesity and Lifestyle study, we assessed the contributions of eGFR (assessed by cystatin C (eGFRcysC) and serum creatinine (eGFRcr) and albuminuria (uACR) to total and CVD mortality. Results After adjusting for age, sex, CVD risk factors and uACR, compared with an eGFRcysC >90 mL/min per 1.73 m2, eGFRcysC <60 mL/min per 1.73 m2 was associated with 56% and 73% increases in the risks for all-cause and CVD mortality, respectively. The respective changes for the c-statistic when eGFRcysC was added to a risk prediction model were 0.003 (95% confidence interval: 0.001 to 0.005) and 0.002 (95% confidence interval: −0.001 to 0.006). The net proportion of non-events assigned a lower-risk category significantly improved with the addition of eGFR (non-event net reclassification index eGFRcr: 1.0% and eGFRcysC: 1.5%) for all-cause mortality, but for CVD mortality, improvements were only significant when eGFR was combined with uACR. The net proportion of events assigned a higher-risk category was not significantly improved. Conclusion In our community-based cohort, reduced eGFRcysC was associated with all-cause and CVD mortality. The addition of chronic kidney disease measures to risk prediction models improved overall risk stratification among those at low risk as opposed to those at high baseline risk of mortality. [ABSTRACT FROM AUTHOR]

The article provides an analysis of the management and reporting of haemolysed specimens. Topics discussed include impact of haemolysis of blood samples on laboratory test results, interference with immunoassays, and guidelines from Australasian Association of Clinical Biochemists (AACB) including correct collection techniques from laboratories, need to provide education and training to staff involved in collection of blood samples, and impact of H-Index levels.

Objectives: To examine whether combined vitamin D and calcium supplementation improves insulin sensitivity, insulin secretion, β-cell function, inflammation and metabolic markers. Design: 6-month randomized, placebo-controlled trial. Participants: Ninety-five adults with serum 25-hydroxyvitamin D [25(OH)D] ≤55 nmol/L at risk of type 2 diabetes (with prediabetes or an AUSDRISK score ≥15) were randomized. Analyses included participants who completed the baseline and final visits (treatment n = 35; placebo n = 45). Intervention: Daily calcium carbonate (1,200 mg) and cholecalciferol [2,000–6,000 IU to target 25(OH)D >75 nmol/L] or matching placebos for 6 months. Measurements: Insulin sensitivity (HOMA2%S, Matsuda index), insulin secretion (insulinogenic index, area under the curve (AUC) for C-peptide) and β-cell function (Matsuda index x AUC for C-peptide) derived from a 75 g 2-h OGTT; anthropometry; blood pressure; lipid profile; hs-CRP; TNF-α; IL-6; adiponectin; total and undercarboxylated osteocalcin. Results: Participants were middle-aged adults (mean age 54 years; 69% Europid) at risk of type 2 diabetes (48% with prediabetes). Compliance was >80% for calcium and vitamin D. Mean serum 25(OH)D concentration increased from 48 to 95 nmol/L in the treatment group (91% achieved >75 nmol/L), but remained unchanged in controls. There were no significant changes in insulin sensitivity, insulin secretion and β-cell function, or in inflammatory and metabolic markers between or within the groups, before or after adjustment for potential confounders including waist circumference and season of recruitment. In a post hoc analysis restricted to participants with prediabetes, a significant beneficial effect of vitamin D and calcium supplementation on insulin sensitivity (HOMA%S and Matsuda) was observed. Conclusions: Daily vitamin D and calcium supplementation for 6 months may not change OGTT-derived measures of insulin sensitivity, insulin secretion and β-cell function in multi-ethnic adults with low vitamin D status at risk of type 2 diabetes. However, in participants with prediabetes, supplementation with vitamin D and calcium may improve insulin sensitivity. Trial Registration: Australian New Zealand Clinical Trials Registry [ABSTRACT FROM AUTHOR]

Background: There has been recent evidence suggesting the presence of anti-thyroid peroxidase antibodies (TPOAb) increases the risk of miscarriage, and levothyroxine can rescue miscarriages associated with TPOAb. We propose the most clinically pragmatic cohort to screen for TPOAb are women presenting for management of a missed miscarriage and have never birthed a liveborn. We measured serum TPOAb among nulliparous women presenting for management of miscarriage, and compared levels with women who have had 2 or more livebirths (and never miscarried). Given its potential role in immunomodulation, we also measured Vitamin D levels. Methods: We performed a prospective descriptive cohort study at a tertiary hospital (Mercy Hospital for Women, Victoria, Australia). We measured TPOAb and Vitamin D levels in serum obtained from 118 nulliparous women presenting for management of miscarriage, and 162 controls with 2 or more livebirths (and no miscarriages). Controls were selected from a serum biobank prospectively collected in the first trimester at the same hospital. Results: Nulliparous women with 1 or more miscarriages had higher thyroid peroxidase antibody (TPOAb) levels than those with 2 or more livebirths; TPOAb in miscarriage group was 0.3 mIU/L (interquartile range [IR]: 0.2-0.7) vs 0.2 mIU/L among controls (IR 0.0-0.5; p < 0.0001). We confirmed TPOAb levels were not correlated with serum human chorionic gonadotrophin (hCG) concentrations in either the miscarriage or control groups. In contrast, thyroid stimulating hormone, fT3 and fT4 levels (thyroid hormones) either trended towards a correlation, or were significantly correlated with serum hCG levels in the two groups. Of the entire cohort that was predominantly caucasian, only 12% were Vitamin D sufficient. Low Vitamin D levels were not associated with miscarriage. Conclusions: We have confirmed the association between miscarriage and increased TPOAb levels. Furthermore, it appears TPOAb levels in maternal blood are not influenced by serum hCG levels. Therefore, we propose the day nulliparous women present for management for miscarriage is a clinically relevant, and pragmatic time to screen for TPOAb. [ABSTRACT FROM AUTHOR]

Although manufacturers are compelled by the European IVD Directive, 98/79/EC, to have traceability of the values assigned to their calibrators if suitable higher order reference materials and/or procedures are available, there is still no equivalence of results for many measurands determined in clinical laboratories. The adoption of assays with metrological traceable results will have a significant impact on laboratory medicine in that results will be equivalent across different laboratories and different analytical platforms. The IFCC WG on Allowable Errors for Traceable Results has been formed to define acceptable limits for metrological traceability chains for specific measurands in order to promote the equivalence of patient results. These limits are being developed based on biological variation for the specific measurands. Preliminary investigations have shown that for some measurands, it is possible for manufacturers to assign values to assay calibrators with a measurement uncertainty that allows the laboratory enough combined uncertainty for their routine measurements. However, for other measurands, e.g., plasma sodium, current assays are too imprecise to fulfil limits based on biological variation. Although an alternative approach based on probability theory is being investigated, the most desirable approach would be for industry to improve measurement methods so that they meet clinical requirements. [ABSTRACT FROM AUTHOR]

Objective Vitamin D deficiency is recognized as a global public health problem, but the population-based prevalence of deficiency and its determinants in Australian adults is not known. This study evaluated the vitamin D status of Australian adults aged ≥25 years and risk factors associated with vitamin D deficiency in this population. Design and Patients We studied a national sample of 11 247 Australian adults enrolled in the 1999/2000 Australian Diabetes, Obesity and Lifestyle (AusDiab) study drawn from 42 randomly selected districts throughout Australia. Measurements Serum concentrations of 25-hydroxyvitamin D [25(OH)D] were measured by immunoassay. Vitamin D deficiency was defined as a concentration <50 nmol/l. Information on demographic and lifestyle factors was derived from interview-administered questionnaires. Results The mean serum 25(OH)D concentration was 63 nmol/l (95% CI: 59-67 nmol/l). Only 4% of the population had a level <25 nmol/l, but the prevalence of vitamin D deficiency (<50 nmol/l) was 31% (22% men; 39% women); 73% had levels <75 nmol/l. The prevalence of vitamin D deficiency increased significantly with age, was greater in women, in those of non-Europid origin, in the obese and those who were physically inactive and with a higher level of education. Deficiency was also more common during winter and in people residing in southern Australia (latitude >35°S); 42% of women and 27% of men were deficient during summer-autumn, which increased to 58% and 35%, respectively, during winter-spring. Conclusion Vitamin D deficiency is common in Australia affecting nearly one-third of adults aged ≥25 years. This indicates that strategies are needed at the population level to improve vitamin D status of Australians. [ABSTRACT FROM AUTHOR]

Laboratory diagnostics (i.e., the total testing process) develops conventionally through a virtual loop, originally referred to as 'the brain to brain cycle' by George Lundberg. Throughout this complex cycle, there is an inherent possibility that a mistake might occur. According to reliable data, preanalytical errors still account for nearly 60%-70% of all problems occurring in laboratory diagnostics, most of them attributable to mishandling procedures during collection, handling, preparing or storing the specimens. Although most of these would be 'intercepted' before inappropriate reactions are taken, in nearly one fifth of the cases they can produce inappropriate investigations and unjustifiable increase in costs, while generating inappropriate clinical decisions and causing some unfortunate circumstances. Several steps have already been undertaken to increase awareness and establish a governance of this frequently overlooked aspect of the total testing process. Standardization and monitoring preanalytical variables is of foremost importance and is associated with the most efficient and well-organized laboratories, resulting in reduced operational costs and increased revenues. As such, this article is aimed at providing readers with significant updates on the total quality management of the preanalytical phase to endeavour further improvement for patient safety throughout this phase of the total testing process. [ABSTRACT FROM AUTHOR]

Objective: To examine whether serum 25-hydroxyvitamin D (25OHD) and dietary calcium predict incident type 2 diabetes and insulin sensitivity.Research Design and Methods: A total of 6,537 of the 11,247 adults evaluated in 1999-2000 in the Australian Diabetes, Obesity and Lifestyle (AusDiab) study, returned for oral glucose tolerance test (OGTT) in 2004-2005. We studied those without diabetes who had complete data at baseline (n = 5,200; mean age 51 years; 55% were women; 92% were Europids). Serum 25OHD and energy-adjusted calcium intake (food frequency questionnaire) were assessed at baseline. Logistic regression was used to evaluate associations between serum 25OHD and dietary calcium on 5-year incidence of diabetes (diagnosed by OGTT) and insulin sensitivity (homeostasis model assessment of insulin sensitivity [HOMA-S]), adjusted for multiple potential confounders, including fasting plasma glucose (FPG).Results: During the 5-year follow-up, 199 incident cases of diabetes were diagnosed. Those who developed diabetes had lower serum 25OHD (mean 58 vs. 65 nmol/L; P < 0.001) and calcium intake (mean 881 vs. 923 mg/day; P = 0.03) compared with those who remained free of diabetes. Each 25 nmol/L increment in serum 25OHD was associated with a 24% reduced risk of diabetes (odds ratio 0.76 [95% CI 0.63-0.92]) after adjusting for age, waist circumference, ethnicity, season, latitude, smoking, physical activity, family history of diabetes, dietary magnesium, hypertension, serum triglycerides, and FPG. Dietary calcium intake was not associated with reduced diabetes risk. Only serum 25OHD was positively and independently associated with HOMA-S at 5 years.Conclusions: Higher serum 25OHD levels, but not higher dietary calcium, were associated with a significantly reduced risk of diabetes in Australian adult men and women. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To examine whether serum 25-hydroxyvitamin D (25OHD) and dietary calcium predict incident type 2 diabetes and insulin sensitivity. RESEARCN DESIGN AND METHODS--A total of 6,537 of the 11,247 adults evaluated in 1999--2000 in the Australian Diabetes, Obesity and Lifestyle (AusDiab) study, returned for oral glucose tolerance test (OGTT) in 2004-2005. We studied those without diabetes who had complete data at baseline (n = 5,200; mean age 51 years; 55% were women; 92% were Europids). Serum 25OHD and energy-adjusted calcium intake (food frequency questionnaire) were assessed at baseline. Logistic regression was used to evaluate associations between serum 25OHD and dietary calcium on 5-year incidence of diabetes (diagnosed by OGTT) and insulin sensitivity (homeostasis model assessment of insulin sensitivity [HOMA-S]), adjusted for multiple potential confounders, including fasting plasma glucose (FPG). RESULTS--During the 5-year follow-up, 199 incident cases of diabetes were diagnosed. Those who developed diabetes had lower serum 25OHD (mean 58 vs. 65 nmol/L; P < 0.001) and calcium intake (mean 881 vs. 923 mg/day; P = 0.03) compared with those who remained free of diabetes. Each 25 nmol/L increment in serum 25OHD was associated with a 24% reduced risk of diabetes (odds ratio 0.76 [95% CI 0.63-0.92]) after adjusting for age, waist circumference, ethnicity, season, latitude, smoking, physical activity, family history of diabetes, dietary magnesium, hypertension, serum triglycerides, and FPG. Dietary calcium intake was not associated with reduced diabetes risk. Only serum 25OHD was positively and independently associated with HOMA-S at 5 years. CONCLUSIONS--Higher serum 25OHD levels, but not higher dietary calcium, were associated with a significantly reduced risk of diabetes in Australian adult men and women. [ABSTRACT FROM AUTHOR]

Objective Recent studies report an association between maternal thyroid auto-antibodies and preterm birth. None have made the important distinction between spontaneous and iatrogenic preterm birth. We investigated the association between spontaneous preterm birth before 35-week gestation and both thyroid function and auto-antibody status. Design Retrospective nested case–control study, samples retrieved from a biobank of around 8000 samples. Patients Forty-six cases of spontaneous preterm birth <35-weeks gestation compared with 124 cases who delivered at 40 weeks gestation, matched for maternal age and duration of serum storage. All resulted in a singleton liveborn. Measurements First trimester serum levels of TSH, free T4, free T3, anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies. Results Women who had a preterm birth delivered at a median gestational age of 33 (+1 day) weeks gestation (controls 40 + 3 weeks) and had significantly lower birthweight infants [mean (range) weight 1965 (581–3117) grams compared with controls 3526 (2685–4760) grams]. Median levels of anti-thyroglobulin and anti-TPO antibodies were similar in the two groups (Anti-Tg: 3 IU/ml (Range 1–316) v 3 IU/ml (1–691); Anti-TPO 8 IU/ml (3–73) v 9 IU/ml (3–499); P ≥ 0·18 for both comparisons, compared using three statistical models). In the preterm group, the median TSH level was 0·70 mIU/l (range 0·04–3·84), similar to controls (0·88 (0·01–2·87), P = 0·1). Free T3 and T4 levels were also similar in both groups. Conclusions Thyroid function and thyroid autoantibody status among women who have a spontaneous preterm delivery before 35 weeks gestation are not different from women delivering at term. [ABSTRACT FROM AUTHOR]

Aims: Cardiac troponin levels predict mortality and cardiovascular events in asymptomatic patients receiving dialysis and may be a useful clinical tool to stratify high-risk asymptomatic individuals. Methods: The present study examined levels of troponins I (cTnI) and T (cTnT) in patients with chronic renal impairment, patients receiving dialysis and renal transplant recipients. Patients receiving dialysis on the renal transplant waiting list were compared with those excluded from the list based on medical criteria. Median levels were compared using the Kruskal–Wallis test and proportions compared by chi-squared. Results: Median troponin levels were higher in patients on dialysis than transplant recipients. Comparing patients receiving dialysis not listed compared with those listed for renal transplant, median cTnI levels were significantly higher (0.03 versus 0.02 µg/L, P < 0.01) whereas median cTnT levels were not. Patients listed for transplantation were younger, had less clinical cardiovascular disease and lower C-reactive protein than those awaiting renal transplantation. The proportion of patients with elevated cTnT was not substantially different between patients awaiting renal transplantation (38%) and those excluded (52%). Levels of cTnI and cTnT were inversely related to renal function in predialysis and transplant patients, but were not related to time on dialysis for those receiving dialysis therapy. Conclusion: As patients awaiting renal transplantation are clinically screened for cardiovascular disease but have frequently elevated cardiac troponin levels, troponin may be a useful clinical tool to identify high-risk asymptomatic patients on dialysis prior to renal transplantation. The influence of renal function on the interpretation of cardiac troponin and risk prediction requires further evaluation. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical usefulness for the measurement of testosterone (T) values in the “low” female range with a direct radioimmunoassay (RIA) for total T by comparing total T values measured by this assay with values determined by conventional RIA after organic solvent extraction/column chromatography. Design: Cross-sectional study. Setting: Victoria, Australia. Patient(s): Two hundred fifty-nine healthy women, aged 18–75 years, recruited from the community. Intervention(s): Fasting serum samples were obtained and stored at −80°C. Main Outcome Measure(s): Total T measurement. Total T was measured by the direct RIA method using antibody-coated tubes and iodine-labeled T tracer. For comparison, total T levels were also measured using the conventional RIA method after organic solvent (ethyl acetate:hexane [3:2]) extraction and celite column partition chromatography before RIA. Result(s): The mean T level by direct RIA was 0.76 nmol/L (median, 0.70; SD, 0.54; minimum, 0.10; maximum, 3.2). The mean difference between the two measurements (direct RIA − conventional RIA) was −0.28 (SD, 0.3). The direct RIA value was 63% (95% confidence interval, 26%–155%) of the conventional RIA estimate. For the classification of values at the lower end of the range, there was very good agreement beyond chance (kappa = 0.68–0.74) for values in approximately the lowest 10th–40th percentiles. Conclusion(s): The direct RIA is a clinically useful assay for the study of the issue of “low” T within the female population. [Copyright &y& Elsevier]

The article highlights the revision of the original hierarchy established by the Stockholm Conference on Quality Specifications in Laboratory Medicine, presented at the 1st Strategic Conference of the European Federation of Clinical Chemistry and Laboratory Medicine on November 24-25, 2014. The revision includes the three different models to set analytical performance specifications and performance specifications for pre- and post-analytical phases.

OBJECTIVE -- To evaluate A1C for screening and diagnosis of undiagnosed type 2 diabetes defined by oral glucose tolerance testing in clinical and general populations. RESEARCH DESIGN AND METHODS-- A1C cut offs (≤5.5% to rule out diabetes; ≥7.0% to rule in diabetes) were derived from a clinical group (Melbourne Pathology [MP] group: n = 2,494; undiagnosed diabetes 34.6%) and then evaluated in a population-based sample (AusDiab group: n = 6,015; undiagnosed diabetes 4.6%). RESULTS -- For diabetes in the MP and AusDiab groups, A1C at 5.5% gave sensitivities of 98.7 and 83.5%, while A1C at 7.0% gave specificities of 98.2 and 100%, respectively. Many (61.9-69.3%) with impaired A1C (5.6-6.9%) in both populations had abnormal glucose status. CONCLUSIONS -- A1C ≤5.5% and ≥7.0% predicts absence or presence of type 2 diabetes, respectively, while at A1C 6.5-6.9% diabetes is highly probable in clinical and population settings. A high proportion of people with impaired A1C have abnormal glucose status requiring follow-up. [ABSTRACT FROM AUTHOR]