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Measurement uncertainties in clinical chemistry are commonly regarded as heteroscedastic - having a constant relative standard deviation irrespective of the concentration of the measurand. The uncertainty is usually determined at two concentrations using stabilized control materials and assumed to represent the analytical goal. The purpose of the present study was to use duplicates of unselected patient samples to calculate the absolute and relative repeatability component of the intra-laboratory measurement uncertainty from duplicates, using the Dahlberg formula and analysis of variance components. Estimates were made at five different concentration intervals of ALT, AST, Calcium, Cholesterol, Creatinine, CRP, Triglycerides and TSH covering the entire concentration interval of the patient cohort. This partioning allows detailing their repeatability profiles. The calculations of the profiles were based on randomly selected results from sets of duplicates ranging from 12,000 to 65,000 pairs. The repeatability of the measurands showed substantial variability within the measuring interval. Therefore, characterizing imprecision profiles as purely homo- or heteroscedastic or by a single number may not be optimal for the intended use. The present data make a case for nuancing the evaluation of analytical goals and minimal differences of measurement results by establishing uncertainty profiles under repeatability conditions, using natural patient samples. Funding Agencies|Karolinska university laboratory; County council of Ostergotland

Measurement uncertainty (MU) can be estimated and calculated by different procedures, representing different aspects and intended use. It is appropriate to distinguish between uncertainty determined under repeatability and reproducibility conditions, and to distinguish causes of variation using analysis of variance components. The intra-laboratory MU is frequently determined by repeated measurements of control material(s) of one or several concentrations during a prolonged period of time. We demonstrate, based on experimental results, how such results can be used to identify the repeatability, pure reproducibility and intra-laboratory variance as the sum of the two. Native patient material was used to establish repeatability using the Dahlberg formula for random differences between measurements and an expanded Dahlberg formula if a non-random difference, e.g. bias, was expected. Repeatability and reproducibility have different clinical relevance in intensive care compared to monitoring treatment of chronic diseases, comparison with reference intervals or screening. Funding Agencies|Karolinska university laboratory; County council of Ostergotland

Dr. Sadler has very kindly commented our report ‘Measurement repeatability profiles of eight frequently requested measurands in clinical chemistry determined by duplicate measurements of patient sa...

The majority of subarachnoid hemorrhage (SAH) is diagnosed using imaging techniques. The sensitivity of computed tomography scans decreases with increasing time after the bleeding event which can lead to false negative CT scans. Spectrophotometry and microscopic investigations of the cerebrospinal fluid (Csf) can provide additional diagnostic support, but may not be available for emergency diagnoses. Csf-Ferritin has been suggested as an alternative additional marker for SAH that present late and has a potency to be measured in a routine laboratory.A routine Ferritin chemiluminescent assay (Dimension Vista) was compared with a branded and CE-marked Csf-Ferritin nephelometric assay (BN ProSpec) using surplus routine patient samples. We calculated imprecision at pertinent concentrations, compared patient samples, and established reference intervals.The standard deviation was about a third for the Dimension Vista assay compared to that of the BN ProSpec assay at the three tested concentrations. The correlation showed a systematic difference between the methods but the correlation was high (r = 0.955). Accordingly, the reference intervals were higher for the BN ProSPec (2.7-16.8 μg/L) than for the Dimension Vista (2.0-12.6 μg/L).The precision of the Dimension Vista measurements was considerably better than that of the BN ProSpec. The Dimension Vista results correlated well with those of the comparative method, yielding slightly lower values. This is reflected in the reference intervals. These findings permit the use of the routinely available Ferritin assay of the Dimension Vista for measuring Csf-Ferritin and complementing the late diagnosis of SAH outside office hours of specialized Csf laboratories.

Results of measurements of quantities in laboratory medicine are used for diagnosis, prediction and monitoring of disease. Evaluation of results is based on evidence and practical experience. In both cases consistency and transferability of results is needed. For diagnosis and prediction a result is compared to a reference value or reference interval whereas in monitoring it is more important to compare results of measurements with previous results. The analytical goals may therefore vary depending on the intended use of the results and both trueness and precision will need to be considered. The analytical goals may also be influenced by the disease characteristics. A brief review of available methods and principles will be given.

Pre-eclampsia is associated with both maternal and foetal complications. Several studies have shown increased trophoblast apoptosis in the placenta of women with this condition. The aim of this study was to investigate whether increased apoptosis can be detected as elevated levels of an apoptotic product in serum samples from women with pre-eclampsia. For this purpose, we used the M30-Apoptosense ELISA assay, which measures a neo-epitope of cytokeratin 18 that is exposed after cleavage by caspases during apoptosis of epithelial cells (M30 antigen). The M30-antigen concentrations were measured in the sera of 15 healthy pregnant women and 15 patients with pre-eclampsia (gestation weeks 24-34). Patients with pre-eclampsia had significantly higher serum M30-antigen concentrations, median 120 U/L, compared to 15 healthy pregnant women matched for pregnancy length, median 104 U/L (p = 0.01). This is consistent with previous findings of increased trophoblast apoptosis in women with pre-eclampsia and raises the possibility that M30-antigen can be used as a serum marker for the severeness of this condition for the mother and child.

The Modification of Diet in Renal Disease Study equation-estimated glomerular filtration rate (MDRD-eGFR) as a marker for chronic kidney disease, with a single decision level for both genders and all adult ages, requires that the calculated quantity is independent of gender and age. In a retrospective study of S-Creatinine concentrations from laboratory information systems of hospitals in the UK and Sweden, comprising about 140,000 results in total, it was found that the MDRD-eGFR indeed differs between genders and that it varies with age more than the S-Creatinine concentration does. If the age compensation is deleted from the algorithm, the relative changes in the MDRD-eGFR decrease and become almost the same as those for S-Creatinine concentrations. The difference between the genders could probably be overcome by increasing the "if female factor". We used Pt-Iohexol and S-Creatinine concentrations measured simultaneously to estimate the performance of the MDRD-eGFR in relation to Pt-Iohexol clearance. The Pt-Iohexol varies considerably between patients with the same S-Creatinine concentrations, a difference that is not reflected in the MDRD-eGFR. It is concluded that the mathematical transformation of S-Creatinine concentrations does not add any diagnostic value. On the contrary, an increased measurement uncertainty is unavoidable with the use of factors and exponents. The uncertainty is greater than any difference between age and gender in adjacent age groups. There is no compensation for the individual relation between S-Creatinine and Iohexol clearance, and the equation does not consider the individual body surface area; it is therefore inadvisable to use the MDRD-eGFR values as the basis for administration of drugs excreted by the kidneys.

Objectives To characterize dynamics of changes of serum levels of TGF-β1 and TNF-α in rats with cardiac fibrosis (CF) occurring during chronic renal failure (CRF), and to reveal the character pf correlations of these factors with amounts of cardiac collagen. Design and Methods. CRF was induced by unilateral nephrectomy and by electrocoagulation of 25% of the cortex of remnant kidney. Post-operative checkpoints were 2, 4, and 6 months. Serum TGF-β1 and TNF-α levels were measured by ELISA. Results. CF became pronounced only at 6 months of CRF, while serum TGF-β1 concentrations reached maximum at 4 months, i.e., at the checkpoint preceding the development of CF. Multiple regression showed cardiac collagen to correlate with both serum TGF-β1 levels and time from the onset of CRF. Sensitivity and specificity of TGF-β1 as serum marker of CF were 86% and 75%.

A comparison of the performance, at two concentrations, of the measurement procedures for 23 common components is presented. For each component the within-, pure between- and total variations have been calculated and an imprecision profile indicated. Thus a pragmatic, readily and generally applicable method is advised to describe the performance of laboratories under repeatability and reproducibility conditions. The calculated total variation is compared with the results estimated from the biological variation of the properties. In most cases the within-laboratory variation is better than that given by the reference database, whereas in about half of the procedures the total variation exceeds that of the reference database. The outcome illustrates the transferability problems that multicentre studies and the diagnosis of patients face by measuring samples using a conglomerate of instruments/laboratories that are not aligned. The calculation procedures are detailed in an appendix and the calculation and presentation of the results are made with a custom-made worksheet program.

Development of quality manuals is a means for the promotion of quality in clinical laboratories by describing the total quality system. It also provides opportunity of checking whether the quality system is implemented in reality and demonstrates to the hospital administration and the clinicians that the laboratory is committed to quality. The intention of these guidelines is to describe the elements of the quality system for a large clinical laboratory, and to presentate such a system in the form of a quality manual. The proposed guidelines comply, where relevant, with ISO/IEC guide 25 ‘General requirements for the technical competence of testing laboratories’ and EN 45001 ‘General criteria for the operation of testing laboratories’. The document may be used as an aid for laboratories wishing to be accredited according to EN 45001, or intending to apply for formal certification of their quality systems, according to ISO 9001 ‘Quality systems - Model for quality assurance in design/development, production...

A study of psychosocial job factors and physiological states was conducted using 150 men, aged between 25 and 60, working in six widely different occupations—freight handlers, aircraft mechanics, air traffic controllers, physicians, waiters and symphony musicians. The aim of the study was to characterize any differences in physiological parameters in relation to differences in psychosocial job characteristics. Analyses of variance were used to test differences between groups. The results indicated that waiters, the group reporting the most unfavourable working conditions, tended to have many cardiovascular risk factors. Physicians, who had relatively few cardiovascular risk factors, reported high decision latitude and many emotional reactions in their daily life and had relatively high cortisol and low prolactin levels in plasma.

Reagent strips are frequently used in the practice of laboratory medicine as well as outside the professional laboratories. In the present report, a scheme is presented which allows a reproducible description of the performance of reagent strips. This is exemplified using strips intended for estimation of urinary albumin and glucose. Experimental conditions that are particularly important for these components are given. Suitable and necessary items which should be included in the protocol presenting results of an evaluation are listed. The guidelines might have general applicability in evaluation and description of tests with a limited number of possible results.

Serum from patients was pooled, filtered, dispensed and frozen. The serum pool obtained was used for accuracy control in twenty-one participating laboratories in the Stockholm area. Mean values (state of art values) were obtained for creatinine, cholesterol, glucose, urea and uric acid. These values were compared with values obtained with highly accurate reference methods, based on isotope dilution--mass fragmentography. The most marked difference was found in the case of determination of creatinine. It is suggested that immediate access to such a well-defined human serum might decrease the need for conventional interlaboratory control programmes.

In the present study, 58 relatives of cancer patients (50 women and 8 men, mean age 53) who experienced the grief and tension induced by severe illness in the family were followed. The aim of the study was to examine possible associations between anxiety, depression, and mental exhaustion, on one hand, and glycosylated hemoglobin (HbAlC) level and changes in HbAlC level on the other hand. The relatives were studied approximately once a month during part of the patient's period of illness. On each occasion their psychiatric state was evaluated by means of a standardized observation and interview technique. A blood sample in the nonfasting state was taken for HbAlC assay. The main finding is that a high level of anxiety during the course of a close relative's cancer illness is associated with increasing HbAlC levels (p < .01).

Cholesterol was determined by a two-step method. The modification allows accurate analysis of about 100 samples per hour. A cholesterol standard dissolved in TRITON X-100 is described. This composition gives a colour development which more closely resembles that of serum than the conventional standard of cholesterol in glacial acetic acid.