[Results of urinary control analyses of narcotic addicts on methadone therapy. An evaluation in the county of ]rhus in 1993].

Urinary control results were evaluated for 230 drug addicts in methadone therapy in the county of Arhus for 1993. Nine point nine percent of the initial samples were positive for opiates, dropping to 5.9% for subsequent samples, suggesting that urinary control has consequences.

An HPLC-GC/MS reference method for serum total cholesterol with control for ester hydrolysis.

Currently used isotope-dilution mass spectrometry methods for serum total cholesterol are performed without control in each sample for completeness of hydrolysis of cholesterol esters. In order to monitor this step in the analysis, we developed a method based on both high-pressure liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS). 13C3-cholesterol and cholesteryl [1-14C] oleate were added to serum that was saponified and extracted into hexane.

Effect of the biological matrix on the urinary testosterone/epitestosterone ratio measured by gas chromatography/mass spectrometry in doping analysis.

Testosterone doping in sport is detected by measurement of an increased testosterone/epitestosterone (T/E) ratio in urine. The critical limit is 6. The present study concerns calibration curves for the T/E ratio measured by gas chromatography/mass spectrometry (electron impact) according to the guidelines of the International Olympic Committee.

[Paraclinical examination programs in Danish hospitals prior to minor surgical procedures].

Using a questionnaire, paraclinical test programs prior to minor surgery were recorded for Danish hospitals. Sixty-one out of 66 departments of surgery completed the questionnaire. Most of the departments used a basic test program for younger subjects and an extended one for elderly subjects.

Analytical goals for P-bilirubins.

Analytical goals for P-Bilirubins (total) were assessed on the basis of biological variation and "medical needs". Goals for analytical accuracy were from 0.01 to 0.

Analytical goals for accuracy and precision of plasma creatinine determinations evaluated by reference method measurements.

Using approaches based on "medical needs" and biological variation, goals for analytical accuracy were assessed to 0.072-0.15 expressed as relative deviations, and goals for analytical precision were estimated to 0.

HPLC with enzymatic detection as a candidate reference method for serum creatinine.

We present a candidate Reference Method for determining the concentration of serum creatinine. The method is based on HPLC combined with enzymatic determination. Creatinine plus 14[C]creatinine is extracted by cation-exchange chromatography, subjected to reversed-phase HPLC, and finally quantified enzymatically.

Mean and variance rules are more powerful or selective than quality control rules based on individual values.

Quality control rules based on individual values are compared with mean and variance rules using theoretical computations and simulations. Simple (1(3)s) and combined individual value rules, e. g.

Estimation of the linear relationship between the measurements of two methods with proportional errors.

The linear relationship between the measurements of two methods is estimated on the basis of a weighted errors-in-variables regression model that takes into account a proportional relationship between standard deviations of error distributions and true variable levels. Weights are estimated by an interative procedure. As shown by simulations, the regression procedure yields practically unbiased slope estimates in realistic situations.

The between-run component of variation in internal quality control.

Design of control charts for the mean, the within-run component of variance, and the ratio of between-run to within-run components of variance is outlined. The between-run component of variation is the main source of imprecision for analytes determined by an enzymo- or radioimmunoassay principle; accordingly, explicit control of this component is especially relevant for these types of analytes. Power curves for typical situations are presented.

Assessing diagnostic tests by a strictly proper scoring rule.

Evaluation of univariate quantitative diagnostic tests by strictly proper scoring rules is considered as an alternative to the traditional error rate measures. In principle, the posterior probability of disease as a function of the test value is estimated from training observations, and subsequently the score is assessed on a set of test samples. The same subjects may serve as training and test samples when the bootstrap procedure is applied for estimation of standard errors and correction of bias.

Choosing quality-control systems to detect maximum clinically allowable analytical errors.

Critical systematic and random analytical errors for 17 common clinical chemical components were estimated from published values for analytical imprecision, biological variation, and "medically important changes." Appropriate quality-control systems for these analytes are discussed on the basis of power considerations. The simple rule 1(3)s, with one control per run, is minimally sufficient for the analytes (about one quarter of those considered here) for which the magnitude of critical error is at least 3 analytical standard deviations.

A review on the methodology for assessing diagnostic tests.

Evaluation of diagnostic tests by the following principles are reviewed: error rates, scores based on posterior probabilities, and the excess loss considered in a decision theoretic context. Error rates or the complementary non-error rates, specificity and sensitivity, are simple measures which provide a rough indication of the discriminative value. In clinical practice, where a test serves as a decision support together with other information, conversion of test results to posterior probabilities is recommended.

On the sensitivity of linear discriminant analysis to sampling variation and analytical errors.

The influence of analytical inaccuracy and imprecision on the linear discriminant function is considered. Analytical shifts occurring between the analysis of samples from each of two groups give spuriously low error rates if the function is evaluated on the training set, notably at high dimensions. Inaccuracy arising after the establishment of a discriminant function may change considerably the individual group error rates whereas the overall error rate is moderately affected.

Two-stage transformation systems for normalization of reference distributions evaluated.

In two-stage transformation systems for normalization of reference distributions, the asymmetry is first corrected, and any deviation of kurtosis is then adjusted. The simulation studies reported here show that these systems have previously been assessed too optimistically because the sample variation of the transformation parameters was neglected. Applying a goodness-of-fit test to transformed values shows that one should accept gaussianity only for p-values greater than 0.

Comparison of quantitative diagnostic tests: type I error, power, and sample size.

For a quantitative laboratory test the 0.975 fractile of the distribution of reference values is commonly used as a discrimination limit, and the sensitivity of the test is the proportion of diseased subjects with values exceeding this limit. A comparison of the estimates of sensitivity between two tests without taking into account the sampling variation of the discrimination limits can increase the type I error to about seven times the nominal value of 0.

Assessing diagnostic tests once an optimal cutoff point has been selected.

The specificity and sensitivity of a quantitative diagnostic test depends on the chosen cutoff point. The common practice of selecting a cutoff point that maximizes the specificity plus the sensitivity, as judged from the observed test results, is studied here by simulation. Test performance is on average assessed too optimistically by this procedure--a phenomenon of importance when sample sizes are small.

Analysis of insulin receptors on heterogeneous eukaryotic cell populations with fluorochrome-conjugated insulin and fluorescence-activated cell sorter. Advantages and limitations to the 125I-labelled insulin methodology.

The diversity in insulin receptor expression within eukaryotic cell populations can be studied with fluorochrome conjugated reagents with high affinity to the insulin receptor in combination with flow cytometry. We studied the optimal conditions for application of fluorescein isothiocyanate (FITC) conjugated insulin in combination with the fluorescence activated cell sorter (FACS) to analyse insulin receptor expression, and also studied the feasibility of this method for identifying and isolating viable subsets with differences in insulin receptor expression within a cell population. Semisynthetic human insulin was conjugated to FITC, which resulted in at least four types of FITC-insulin molecules with different affinities to the insulin receptor.

Precision of sensitivity estimations in diagnostic test evaluations. Power functions for comparisons of sensitivities of two tests.

The precision of estimates of the sensitivity of diagnostic tests is evaluated. "Sensitivity" is defined as the fraction of diseased subjects with test values exceeding the 0.975-fractile of the distribution of control values.