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E K Harris

Publications and source records attributed to E K Harris.

At least 37 records · Page 2Linked to original sources
PubMed1979

Statistical principles underlying analytic goal-setting in clinical chemistry.

The Survey programs of the College of American Pathologists (CAP) have assessed current levels of analytic variance in many biochemical measurements, and a number of clinical chemists have proposed analytic goals. The practical importance of further reductions in analytic variance depends on the specific use of the laboratory test. Three general areas of application are described: 1) surveying a population to detect disease, 2) determining whether a particular individual's level of a given analyte is above or below a predefined alarm point, 3) monitoring an individual over a period of time to detect trends. Within each of these different contests, statistical methods are proposed for judging the practical effect of improvements in current levels of analytic precision, taking into account recent estimates of biological variation within the average individual and between individuals. As might be expected, reductions in analytic variance have greatest impact in those applications where biological variance is minimal. Such reductions will generally have little effect on the efficiency of a population survey but may be extremely valuable in decision-making concerning a particular hospital patient.

Analysis of Variance↗
PubMed1978

Gallium-67 citrate scanning in the staging of idiopathic pulmonary fibrosis: Correlation and physiologic and morphologic features and bronchoalveolar lavage.

Idiopathic pulmonary fibrosis is a fatal disorder characterized by interstitial fibrosis and parenchymal inflammation. Current concepts of this disease suggest that the inflammation precedes and probably induces the fibrotic state. To evaluate the extent and relative activity of the inflammatory process, we scanned patients with idiopathic pulmonary fibrosis using gallium-67, a radionuclide known to concentrate in regions of inflammation. To quantify the amount of isotope in the lung parenchyma, the 67Ga-index was developed, a parameter derived from estimates of the size of regional pulmonary uptake, the uptake intensity, and its texture. Evaluation of 67Ga scans in 30 patients with idiopathic pulmonary fibrosis and 19 control subjects demonstrated that the 67Ga-index in the group with idiopathic pulmonary fibrosis was significantly higher (P less than 0.001) than that in the control group. When compared with lung biopsy morphologic studies in 22 patients with idiopathic pulmonary fibrosis, the 67Ga-index correlated with the degree of interstitial cellularity (P less than 0.05) and the degree of alveolar cellularity (P less than 0.005). When compared with cellular analysis of bronchoalveolar lavage fluid in 17 patients with idiopathic pulmonary fibrosis, the 67Ga-index correlated with the differential percentage of neutrophils (P less than 0.05), but not lymphocytes, eosinophils, or macrophages. These studies indicate that 67Ga accumulates in the lungs of patients with idiopathic pulmonary fibrosis and is probably associated with the active inflammatory state. The associations of the 67Ga-index with morphologic features and bronchoalveolar lavage analysis suggest that quantitative evaluation of these scans may be useful in staging the activity of idiopathic pulmonary fibrosis and following responses to therapy.

Adult↗
PubMed1977

Comparison of estimates of long-term analytical variation derived from subject samples and control serum.

Variation in the assays of uniform control serum commonly are assumed to represent day-to-day analytical variation. To test this assumption, we compared the differences between results of serum aliquots assayed immediately for 12 constituents and frozen aliquots accumulated and assayed on a single day with the results of control serum variation from the same period. One aliquot of each weekly sample was stored frozen. Eleven subjects were sampled for 12 weeks. Storage at --20 degrees C for 15 weeks had a mild destructive effect on two enzymes in serum. The control serum data revealed significant linear trends in magnesium (upwards) and alkaline phosphatase (downwards) that substantially increased the respective variances. In the other 10 constituents tested, comparison of variances indicated that long-term (weeks) variation in control serum assays is similar to the difference of variation between aliquots assayed immediately and those frozen and assayed at the same time. For these constituents, this finding justifies the use of control serum to estimate long term analytical variation.

Adult↗
PubMed1977

Intra-individual variation of some serum constituents and its relevance to population-based reference ranges.

The advent of high-capacity multi-channel analyzers allows estimation of long-term variability in serum constituents of large numbers of subjects. By frozen storage of specimens with subsequent analysis in a single machine run, long-term analytical variation may be eliminated, thus sharpening the estimates of intra-individual variation. In the present study we used the Vickers M-300 analyzer to obtain the data for such estimates from 37 male volunteers, each bled once a week for 22 weeks. Secimens were analyzed in random order to eliminate any biasing effect of analytical drift during the 4-h machine run. Ten serum constituents were measured. Storage-induced linear trends were small or negligible during the period of specimen collection. Using the ratio of average within-subject variance to the variance among subjects as a guide, serum alkaline phosphatase was found to show the greatest individuality, sodium and potassium the least. Other constitutents showed varying degrees of individuality, but for all these analytes, the usual population-based reference ranges were found to be either insensitive or irrelevant to the study of concentration changes over time within most healthy subjects. Our results generally confirmed those of smaller but comparable earlier studies.

Adult↗
PubMed1976

Some theory of reference values. II. Comparison of some statistical models of intraindividual variation in blood constituents.

Three models of intraindividual variation are reviewed, and statistical methods for distinguishing among them are discussed. Application of these methods to short series of observations from healthy individuals indicates that, in the large majority of cases, a strictly homeostatic model is appropriate for such constituents as serum calcium and magnesium. In less closely controlled variables, e.g., serum cholesterol and uric acid, a nonstationary, "rndom walk" model appears moresuitable in most cases. A more general autoregressive model, which includes the other models as extreme cases, could be used to describe all degrees of homeostatic control. This model is more complex, however, and requires at least 10 observations to yield estimates of acceptable precision. Moreover, it is sensitive to fluctuations in within-batch analytical variance. When biological variance is small relative to analytical variance, all three models yield essentially the same predicated values. To illustrate their use, these models have been applied to four short individual series of cholesterol observations showing increasing amounts of intrapersonal variation over long periods of time. I suggest that when less than 10 observations over time are available, the strictly homeostatic model and the nonstationary model be used to derive a "critical range" for assessing future changes. When longer series are available, the more general model might replace the other two for this purpose, if analytical variation has remained reasonably stable (within +/- 20% of its average value) during the period of observation. Much more experience with the use of all three models in health monitoring programs would be highly desirable.

Analysis of Variance↗
PubMed1975

Some theory of reference values. I. Stratified (categorized) normal ranges and a method for following an individual's clinical laboratory values.

The conventional population-based normal range has recently been shown to be a generally defective reference criterion for assessing individual laboratory test results. Applying a previously derived formula to published data, we find that the use of age-, sex-specific normal ranges may fail to produce a substantial improvement in sensitivity over nonspecific ranges, even when age-sex differences in mean values are statistically significant. This occurs when the difference in means is not accompanied by a sufficient reduction in the variation among individuals within a given class. Turning therefore to comparison of an individual's current measurement with his own previous value(s), I suggest a simple statistical model that leads to sequential testing of each new observation against an exponentially weighted moving average of previous results. Estimates of biological and analytical components of variance are required. The ability of this method to detect trends in very short series is explored with the aid of computer-simulated laboratory data. A sample of these data is also used to illustrate the application of these estimation and testing procedures by means of a graph.

Adult↗