Andrew St John

Ion Selective Electrodes (ISEs) and interferences--a review.

Ion Selective Electrodes (ISEs) are used to measure some of the most critical analytes on clinical laboratory and point-of-care analysers. These analytes which include Na(+), K(+), Cl(-), Ca(2+), Mg(2+) and Li(+) are used for rapid patient care decisions. Although the electrodes are very selective, they are not free of interferences. It is important for laboratories to have an understanding of the type and extent of interferences in order to avoid incorrect clinical decisions and treatment.

The use of urinary dipstick tests to exclude urinary tract infection: a systematic review of the literature.

Several systematic reviews have examined the use of dipstick tests to diagnose or rule in urinary tract infection (UTI). We examined the evidence relating to the use of urine leukocyte esterase and nitrite tests in adults to exclude or rule out UTI. A search of the literature from 1966 to 2003 revealed 30 studies as containing relevant and suitable information and 23 of these, which used a cut-off of 108 colony-forming units per liter, were combined in a meta-analysis. The leukocyte esterase or nitrite test combination, with one or the other test positive, was used in 14 studies, showed the highest sensitivity and the lowest negative likelihood ratio. While there was significant heterogeneity between the studies, 7 of 14 demonstrated significant decreases in pretest to posttest probability with a pooled posttest probability of 5% for the negative result. In certain circumstances, there is evidence for the use of urinalysis as a rule-out test for UTI.

Determinants of Intact Parathyroid Hormone and Free 1,25-Dihydroxyvitamin D Levels in Mild and Moderate Renal Failure

Parameters of calcium and phosphate metabolism were measured in 27 patients with mild renal failure [glomerular filtration rate (GFR) 40-90 ml/min], 12 patients with moderate renal failure (GFR 20-39 ml/min) and in 12 healthy subjects. GFR was determined by technetium-99m diethylenetriamine penta-acetic acid clearance. Intact parathyroid hormone (PTH) was measured by a sensitive immunochemiluminometric assay and somatomedin-C was determined by radioimmunoassay. Both 1,25-dihydroxyvitamin D [1,25(OH)2D] and vitamin-D-binding protein were measured allowing calculation of the free 1,25(OH)2D index. By linear regression and multivariate analysis, PTH was negatively and independently correlated with GFR, plasma bicarbonate and 25-hydroxyvitamin D [25(OH)D] while free 1,25(OH)2D was positively correlated with GFR. Increased PTH secretion and reductions in 1,25(OH)2D were present in mild renal failure patients before any changes in plasma calcium, phosphate and bicarbonate were noted. Plasma alkaline phosphatase was significantly higher in mild chronic renal failure patients compared to normal subjects, possibly indicating early effects of the secondary hyperparathyroidism on the skeleton. Somatomedin-C did not correlate with the free 1,25(OH)2D index or a measure of 1,25(OH)2D production. It is concluded that the secondary hyperparathyroidism which occurs very early in the onset of chronic renal failure may be due to a reduction in the circulating concentration of 1,25(OH)2D consequent upon the renal failure. Low plasma bicarbonate and 25(OH)D also appear to be determinants of a raised PTH concentration. The compensatory increase in PTH presumably maintains extracellular calcium and phosphate levels constant but with possible deleterious effects on the skeleton.

Secondary hyperparathyroidism in patients from Western Australia with hip fracture: relationship to type of hip fracture, renal function, and vitamin D deficiency.

OBJECTIVES: To determine the frequency of vitamin D deficiency and secondary hyperparathyroidism in Australian hip fracture patients living in the community.

IFCC guideline for sampling, measuring and reporting ionized magnesium in plasma.

Abstract Analyzers with ion-selective electrodes (ISEs) for ionized magnesium (iMg) should yield comparable and unbiased results for iMg. This IFCC guideline on sampling, measuring and reporting iMg in plasma provides a prerequisite to achieve this goal [in this document, “plasma” refers to circulating plasma and the forms in which it is sampled, namely the plasma phase of anticoagulated whole blood (or “blood”), plasma separated from blood cells, or serum]. The guideline recommends measuring and reporting ionized magnesium as a substance concentration relative to the substance concentration of magnesium in primary aqueous calibrants with magnesium, sodium, and calcium chloride of physiological ionic strength. The recommended name is “the concentration of ionized magnesium in plasma”. Based on this guideline, results will be approximately 3% higher than the true substance concentration and 4% lower than the true molality in plasma. Calcium ions interfere with all current magnesium ion-selective electrodes (Mg-ISEs), and thus it is necessary to determine both ions simultaneously in each sample and correct the result for Ca2+ interference. Binding of Mg in plasma is pH-dependent. Therefore, pH should be measured simultaneously with iMg to allow adjustment of the result to pH 7.4. The concentration of iMg in plasma may be physiologically and clinically more relevant than the concentration of total magnesium. Furthermore, blood-gas analyzers or instruments for point-of-care testing are able to measure plasma iMg using whole blood (with intact blood cells) as the sample, minimizing turn-around time compared to serum and plasma, which require removal of blood cells. Clin Chem Lab Med 2008;46:21–6.

Comparison of the performance and clinical utility of a carboxy-terminal assay and an intact assay for parathyroid hormone

A comparison of the performance of a two-site immunochemiluminometric assay for intact parathyroid hormone with that of an in-house radioimmunoassay for carboxy terminal parathyroid hormone has been performed on samples from unselected patients being investigated for hypercalcaemia. The intact parathyroid hormone assay was found to be a simple and robust technique with a broad working assay range (CV less than 10% between 1.8-212 pmol/l) and a detection limit of 0.2 pmol/l. Clinically it is superior to the carboxy terminal assay in its ability to distinguish between patients with hyperparathyroidism from those with other causes of hypercalcaemia especially in the presence of impaired renal function.

Innovation in healthcare. The challenge for laboratory medicine

The delivery of healthcare is the product of a complex organization and it is not entirely surprising that innovation is not always considered to deliver on the expectations generated by invention. As policymakers and payers seek to improve the quality and value-for-money of healthcare, more attention is being directed at the barriers to innovation, and the challenges of translating inventions into outcomes. Laboratory medicine is one facet of healthcare that has generated considerable levels of invention but, while showing increasing volumes of activity over the past decades, it has not been recognized for generating the benefit in outcomes that might have been expected. One of the major reasons for this position has been the poor quality of evidence available to demonstrate the impact of laboratory investigations on health outcomes. Consequently an absence of evidence stifles the opportunity to develop the business case that demonstrates the link between test result and improved outcome. This has a major influence on the success of innovation in laboratory medicine. This review explores the process of innovation applied to laboratory medicine and offers an insight into how the impact of laboratory medicine on health outcomes can be improved.

Secondary hyperparathyroidism, vitamin D deficiency and hip fracture: importance of sampling times after fracture

There is controversy about how often elevated parathyroid hormone (PTH) levels are found in hip fracture patients. The aim of this study was to determine whether changes in PTH levels after fracture and surgery could explain some of the variation in published data. Blood samples were obtained from 24 elderly patients with hip fracture before surgery, immediately after surgery and at 2 weeks and 3 months after fracture. PTH levels were elevated (> 5.5 pmol) in 33% initially and then fell significantly at 2 weeks in virtually all subjects (P < 0.001) and remained significantly lower after 3 months (n = 17). Although 25-hydroxyvitamin D levels were low (< 30 nmol) in 44% of the patients, the fall in PTH was not explained by alterations in vitamin D metabolites or other measured parameters. The cause of the variation in PTH levels is unknown but measurements immediately after fracture could overestimate the incidence of secondary hyperparathyroidism. Vitamin D deficiency is common in our hip fracture population and is not influenced by hospitalisation.

Setting analytical performance specifications based on outcome studies – is it possible?

Abstract The 1st Strategic Conference of the European Federation of Clinical Chemistry and Laboratory Medicine proposed a simplified hierarchy for setting analytical performance specifications (APS). The top two levels of the 1999 Stockholm hierarchy, i.e., evaluation of the effect of analytical performance on clinical outcomes and clinical decisions have been proposed to be replaced by one outcome-based model. This model can be supported by: (1a) direct outcome studies; and (1b) indirect outcome studies investigating the impact of analytical performance of the test on clinical classifications or decisions and thereby on the probability of patient relevant clinical outcomes. This paper reviews the need for outcome-based specifications, the most relevant types of outcomes to be considered, and the challenges and limitations faced when setting outcome-based APS. The methods of Model 1a and b are discussed and examples are provided for how outcome data can be translated to APS using the linked evidence and simulation or decision analytic techniques. Outcome-based APS should primarily reflect the clinical needs of patients; should be tailored to the purpose, role and significance of the test in a well defined clinical pathway; and should be defined at a level that achieves net health benefit for patients at reasonable costs. Whilst it is acknowledged that direct evaluations are difficult and may not be possible for all measurands, all other forms of setting APS should be weighed against that standard, and regarded as approximations. Better definition of the relationship between the analytical performance of tests and health outcomes can be used to set analytical performance criteria that aim to improve the clinical and cost-effectiveness of laboratory tests.

Guidelines for sampling, measuring and reporting ionized magnesium in undiluted serum, plasma or blood: International Federation of Clinical Chemistry and Laboratory Medicine (IFCC): IFCC Scientific Division, Committee on Point of Care Testing.

Abstract All analyzers with ion-selective electrodes for ionized magnesium (iMg) should yield comparable and unbiased results. The prerequisite to achieve this goal is to reach consensus on sampling, measurement and reporting. The recommended guidelines for sampling, measurement and reporting iMg in plasma (“plasma” refers to circulating plasma and the forms in which it is sampled: the plasma phase of anticoagulated whole blood, plasma separated from blood cells, or serum) or blood, referring to the substance concentration of iMg in the calibrants, will provide results for iMg that are approximately 3% greater than its true concentration, and 4% less than its true molality. Binding of magnesium to proteins and ligands in plasma and blood is pH-dependent. Therefore, pH should be simultaneously measured to allow adjustment of iMg concentration to pH7.4. The substance concentration of iMg may be physiologically and consequently clinically more relevant than the substance concentration of total magnesium.