- Calculated Chemistry Parameters - do they need to be harmonised? [Review]
- CBClin Biochem Rev 2016; 37(3):131-134
- In clinical chemistry, harmonisation of the testing process is a global initiative with the purpose of improving patient safety, allowing better integration of research data and enabling the use of n...
In clinical chemistry, harmonisation of the testing process is a global initiative with the purpose of improving patient safety, allowing better integration of research data and enabling the use of national electronic heath records. In Australia, as in other countries, the initial focus has been on the harmonisation of the more commonly measured analytes. There are also a number of calculated parameters, derived from these measured analytes, which could also be considered for harmonisation. Calculated parameters that are reported by laboratories and used for clinical decision-making should undergo the same robust process of harmonisation as is the case for the measured analytes. Aspects that should be considered for harmonisation are: terminology, the formulae used and where possible the use of common reference intervals. To investigate pathways towards the harmonisation of calculated parameters, three commonly reported parameters are considered. Calculated osmolality, the anion gap and albumin-adjusted calcium are all derived from common analytes which have individually been considered for harmonisation. They present different methodological, measurement uncertainty and terminological hurdles to harmonisation and are likely to require different pathways and solutions.
- Harmonising Adult Reference Intervals in Australia and New Zealand - the Continuing Story. [Review]
- CBClin Biochem Rev 2016; 37(3):121-129
- Reference intervals (RIs) are used to help clinicians determine if a patient can be classified as being in a diseased or healthy state and there are often sound scientific and clinical reasons for di...
Reference intervals (RIs) are used to help clinicians determine if a patient can be classified as being in a diseased or healthy state and there are often sound scientific and clinical reasons for differences in RIs. One of the current strategic priorities for the Australasian Association of Clinical Biochemists is to encourage and assist laboratories to achieve harmonisation of RIs for common clinical chemistry analytes where sound calibration and traceability are in place. This need is based on good laboratory practice, providing the clinician with results that allow appropriate and reliable clinical interpretation and progression further toward the national e-health framework and a single electronic health record. After reviewing and considering studies related to bias as well as both a priori and a posteriori RI studies nationally and internationally and the consideration of flagging rates and clinical relevance, an initial group of 12 harmonised RIs were endorsed by the Royal College of Pathologists of Australasia in 2014. In 2015, after further stakeholder consultation, a second group of six harmonised RIs for common chemistry analytes has been proposed for adults which includes ALT and AST where methods do not use pyridoxal-5'-phosphate as an activator and lipase excluding the Ortho Clinical Diagnostics and Siemens Dimension assays.
- Harmonisation of Osmolal Gap - Can We Use a Common Formula? [Review]
- CBClin Biochem Rev 2016; 37(3):113-119
- Osmolal gap is the difference between the measured osmolality and a calculated osmolality based on the major commonly measured osmotically active particles. The perceived gap indicates the presence o...
Osmolal gap is the difference between the measured osmolality and a calculated osmolality based on the major commonly measured osmotically active particles. The perceived gap indicates the presence of unmeasured osmotically active particles. The major use of osmolal gap today is to screen for the possible presence of exogenous toxic substances in patients in an emergency department or intensive care unit. There is a long history of osmolal gap calculations and it needs to be appreciated that the uncertainty of the osmolal gap will be determined by the sum of errors in the calculated osmolality, error in measured osmolality and variability in unmeasured analytes. Since 1958 there has been a constant trickle of papers proposing both simple and sophisticated formulae to calculate the 'ultimate' osmolal gap. A gap as close to zero as possible and with a low coefficient of variation across multiple clinical conditions and analytical platforms are also determinants of 'fitness for purpose' of any osmolal gap calculations. The Smithline-Gardner formula for calculated osmolality [2(Na) + Glu + Urea] is fit for purpose in both normal people and general hospital patients. It also performs well across different analytical platforms. This simple formula can be used for rapid mental calculation at the bedside and automated laboratory information system reporting whenever a measured osmolality is requested. In this era of harmonisation, we propose that this formula be adopted by all clinicians and laboratories.
- Harmonising Reference Intervals for Three Calculated Parameters used in Clinical Chemistry. [Review]
- CBClin Biochem Rev 2016; 37(3):105-111
- For more than a decade there has been a global effort to harmonise all phases of the testing process, with particular emphasis on the most frequently utilised measurands. In addition, it is recognise...
For more than a decade there has been a global effort to harmonise all phases of the testing process, with particular emphasis on the most frequently utilised measurands. In addition, it is recognised that calculated parameters derived from these measurands should also be a target for harmonisation. Using data from the Aussie Normals study we report reference intervals for three calculated parameters: serum osmolality, serum anion gap and albumin-adjusted serum calcium. The Aussie Normals study was an a priori study that analysed samples from 1856 healthy volunteers. The nine analytes used for the calculations in this study were measured on Abbott Architect analysers. The data demonstrated normal (Gaussian) distributions for the albumin-adjusted serum calcium, the anion gap (using potassium in the calculation) and the calculated serum osmolality (using both the Bhagat et al. and Smithline and Gardner formulae). To assess the suitability of these reference intervals for use as harmonised reference intervals, we reviewed data from the Royal College of Pathologists of Australasia/Australasian Association of Clinical Biochemists (RCPA/AACB) bias survey. We conclude that the reference intervals for the calculated serum osmolality (using the Smithline and Gardner formulae) may be suitable for use as a common reference interval. Although a common reference interval for albumin-adjusted serum calcium may be possible, further investigations (including a greater range of albumin concentrations) are needed. This is due to the bias between the Bromocresol Green (BCG) and Bromocresol Purple (BCP) methods at lower serum albumin concentrations. Problems with the measurement of Total CO2 in the bias survey meant that we could not use the data for assessing the suitability of a common reference interval for the anion gap. Further study is required.
- Harmonisation and What's in a Unit? [Editorial]
- CBClin Biochem Rev 2016; 37(3):103-104
- Fat-Soluble Vitamins: Clinical Indications and Current Challenges for Chromatographic Measurement. [Review]
- CBClin Biochem Rev 2016; 37(1):27-47
- Fat-soluble vitamins, including vitamins A, D and E, are required for a wide variety of physiological functions. Over the past two decades, deficiencies of these vitamins have been associated with in...
Fat-soluble vitamins, including vitamins A, D and E, are required for a wide variety of physiological functions. Over the past two decades, deficiencies of these vitamins have been associated with increased risk of cancer, type II diabetes mellitus and a number of immune system disorders. In addition, there is increasing evidence of interactions between these vitamins, especially between vitamins A and D. As a result of this enhanced clinical association with disease, translational clinical research and laboratory requests for vitamin measurements have significantly increased. These laboratory requests include measurement of 25-OHD (vitamin D), retinol (vitamin A) and α-tocopherol (vitamin E); the most accepted blood indicators for the assessment of body fat-soluble vitamin (FSV) status. There are significant obstacles to precise FSV measurement in blood. These obstacles include their physical and chemical properties, incomplete standardisation of measurement and limitations in the techniques that are currently used for quantification. The aim of this review is to briefly outline the metabolism and interactions of FSV as a prelude to identifying the current challenges for the quantification of blood vitamins A, D and E.
- An Age-Calibrated Definition of Chronic Kidney Disease: Rationale and Benefits. [Journal Article]
- CBClin Biochem Rev 2016; 37(1):17-26
- Defining chronic kidney disease (CKD) is the subject of intense debate in the current nephrology literature. The debate concerns the threshold value of estimated glomerular filtration rate (eGFR) use...
Defining chronic kidney disease (CKD) is the subject of intense debate in the current nephrology literature. The debate concerns the threshold value of estimated glomerular filtration rate (eGFR) used to make the diagnosis of CKD. Current recommendations argue that a universal threshold of 60 mL/min/1.73m(2) should be used. This threshold has been defended by epidemiological studies showing that the risk of mortality or end-stage renal disease increases with an eGFR below 60 mL/min/1.73m(2). However, a universal threshold does not take into account the physiologic decline in GFR with ageing nor does it account for the risk of mortality and end-stage renal disease being trivial with isolated eGFR levels just below 60 mL/min/1.73m(2) in older subjects and significantly increased with eGFR levels just above 60 mL/min/1.73m(2) among younger patients. Overestimation of the CKD prevalence in the elderly (medicalisation of senescence) and underestimation of CKD (potentially from treatable primary nephrologic diseases) in younger patients is of primary concern. An age-calibrated definition of CKD has been proposed to distinguish age-related from disease-related changes in eGFR. For patients younger than 40 years, CKD is defined by eGFR below 75 mL/min/1.73m(2). For patients with ages between 40 and 65 years, CKD is defined by 60 mL/min/1.73m(2). For subjects older than 65 years without albuminuria or proteinuria, CKD is defined by eGFR below 45 mL/min/1.73m(2).
- Androgen Receptor Structure, Function and Biology: From Bench to Bedside. [Review]
- CBClin Biochem Rev 2016; 37(1):3-15
- The actions of androgens such as testosterone and dihydrotestosterone are mediated via the androgen receptor (AR), a ligand-dependent nuclear transcription factor and member of the steroid hormone nu...
The actions of androgens such as testosterone and dihydrotestosterone are mediated via the androgen receptor (AR), a ligand-dependent nuclear transcription factor and member of the steroid hormone nuclear receptor family. Given its widespread expression in many cells and tissues, the AR has a diverse range of biological actions including important roles in the development and maintenance of the reproductive, musculoskeletal, cardiovascular, immune, neural and haemopoietic systems. AR signalling may also be involved in the development of tumours in the prostate, bladder, liver, kidney and lung. Androgens can exert their actions via the AR in a DNA binding-dependent manner to regulate target gene transcription, or in a non-DNA binding-dependent manner to initiate rapid, cellular events such as the phosphorylation of 2(nd) messenger signalling cascades. More recently, ligand-independent actions of the AR have also been identified. Given the large volume of studies relating to androgens and the AR, this review is not intended as an extensive review of all studies investigating the AR, but rather as an overview of the structure, function, signalling pathways and biology of the AR as well as its important role in clinical medicine, with emphasis on recent developments in this field.
- Variation in Laboratory Reporting of Haemolysis - a Need for Harmonisation. [Journal Article]
- CBClin Biochem Rev 2015; 36(4):133-7
- CONCLUSIONS: There is a need to harmonise the way laboratories report analytes in the presence of haemolysis. This would involve adopting a uniform definition of HI and a protocol for laboratories to confirm for themselves the level of HI at which each analyte is no longer reported, as this is method dependent and so will vary from laboratory to laboratory.
New Search Next
- Aspects to Consider in Adopting Pregnancy-Specific Reference Intervals. [Journal Article]
- CBClin Biochem Rev 2015; 36(4):127-32