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E A Robertson

Publications and source records attributed to E A Robertson.

At least 37 records · Page 2Linked to original sources

Why we need better test evaluations.

A laboratory test is clinically useful only if it successfully answers a question of consequence to patient management. Unfortunately, the results and conclusions of many published test evaluations are misleading or of uncertain validity because common-sense principles of study design are overlooked. This is illustrated by examples from recent literature. We suggest that tests should be evaluated with prospective studies of patients representative of the population for which the test will ultimately be used. The clinical question to be addressed by the test should be clearly stated, and then answered for each patient by means independent of the test being evaluated. When comparing tests with each other, decision levels should be chosen to give either the same sensitivity or specificity for each. The use of soundly designed protocols for the clinical evaluation of tests provides the information needed to select the most effective tests.

Adult↗

Comparison of the effectiveness of four clinical chemical assays in classifying patients with chest pain.

We compared the usefulness of four serum assays for classifying patients originally suspected of having an acute myocardial infarction. One of these is the long-used measurement of total creatine kinase (CK) activity. The other three are relatively new immunoassays: myoglobin by RIA, CK-BB by RIA, and CK-MB by immunoinhibition. When we evaluated test effectiveness with use of conventionally derived reference ranges, the results were misleading. However, by using receiver operating characteristic curves, we were able to effectively compare the four tests at all possible decision levels, rather than at only one. Multiple closely sequential serum specimens were obtained during the first four days after the onset of chest pain. Total CK, CK-MB, and CK-BB all behaved similarly, reaching peak diagnostic effectiveness at 18-20 h, when all three correctly classified 95% of the infarct patients, with a zero false-positive rate. However, total CK was more useful in identifying infarcts later in their courses than were the two CK isoenzyme tests. Myoglobin assay was most effective earlier in the course, at about 7 to 8 h. Our results indicate (a) that the tests for myoglobin and for CK or its isoenzymes are complementary and (b) that of the three CK tests, measurement of total CK activity provides the most information over the broadest segment of a patient's course.

Creatine Kinase↗

Lactate dehydrogenase activity as measured by the SMAC is related to flow-cell energy.

Determination of lactate dehydrogenase (LDH) activity in the SMAC (Technicon) is based on the change in NADH absorbance between two flow cells. We noted that results for patients' specimens and controls changed when the fiber optic terminations for the two LDH channel flow cells were adjusted or "peaked" at the colorimeter chopper assembly. The energy (intensity) of light reaching the flow cells was varied by adjusting the fiber optic terminations, and the absorbance readings for a series of solutions containing NADH and patients' specimens were recorded. For both flow cells, when the fiber optic terminations were adjusted to increase the zero absorbance light intensity from 20 lines to 60 lines, a significant (p less than 0.0001) proportional change was seen in the absorbance readings. Evidently the difference in absorbance between the two flow cells is related not only to the NADH concentrations but also to the difference in the light intensity at the two flow cells. Consequently, changes in the adjustment of the fiber optic terminations produce systematic changes in results for LDH in patients' sera. These systematic changes in LDH results may be minimized by maintaining equivalent settings of the fiber optic terminations for the two flow cells and by using the calibration material with an absorbance most similar to that of patients' specimens.

Autoanalysis↗

Departmental resources and statistics of academic pathology.

The resources needed to operate an academic pathology department have not been evaluated for several years. Fifty academic pathology departments in this country returned a 14-page questionnaire that included information about procedures, personnel, space, and patient load. These data were summarized using means, percentiles, ratios, and linear regression analyses. The average academic pathology department performed more than 5,000 procedures for 1,200 inpatients and outpatients per day and produced 42 publications per year. The results of this study may assist members of the academic pathology community in assessing current and future needs.

Pathology↗

Evaluation of five gentamicin assay procedures for clinical microbiology laboratories.

Five gentamicin assay procedures (a bioassay, an enzyme immunoassay, a latex agglutination inhibition test, a fluorescence immunoassay, and a radioimmunoassay) were evaluated to determine which was optimal for our laboratory. The evaluation was based on recovery and precision studies and results of analyses of patient samples, as well as technical assay performance factors. The latex agglutination inhibition test appears useful for laboratories performing only occasional assays for gentamicin; however, the fact that some rheumatoid factor-positive sera, as well as some other sera for unknown reasons, may give falsely low values is a potential drawback to this procedure. Because of its accuracy, precision, rapid turn-around time, and relative simplicity of performance, we selected the enzyme immunoassay procedure for routine use for gentamicin assays in our laboratory.

Biological Assay↗

Use of receiver operating characteristic curves to evaluate the clinical performance of analytical systems.

The usefulness of an analytical system in patient care is ultimately judged not by its analytical performance but by its clinical performance, i.e., its ability to separate apparently similar patients into two subgroups, one of which has a particular clinically important condition and another subgroup which does not. This clinical performance can be studied with the tools of signal detectability theory, originally developed to analyze the performance of radar and data-transmission systems. Each classification made by an analytical system may be categorized as a true-positive, true-negative, false-positive, or false-negative decision. For laboratory tests the proportion of decisions in each category depends on the biological overlap between the two subgroups, the analytical performance of the system, and the decision level chosen. The clinical performance of the analytical system for all possible decision levels is represented by the receiver operating characteristic curve, which plots the true-positive rate against the false-positive rate. The use of these curves permits comparison of alternative analytical techniques at equal true-positive rates and at all possible decision levels. These comparisons show the effect of analytical improvements on clinical performance.

Chemistry, Clinical↗

Low results for inorganic phosphorus with the SMAC continuous-flow analyzer.

Serum inorganic phosphorus concentrations as measured with the SMAC are lower than those found with other methods. To resolve this problem we analyzed patients' specimens and performed analytical recovery studies with four different systems (SMAC, AutoAnalyzer II, aca, and the Fiske--SubbaRow method). With the SMAC, results for patients' specimens are significantly lower (p less than 0.0001) than with any of the other three methods. The SMAC recovered only about 87% of the added inorganic phosphorus. The value assigned to SMAC Reference I for inorganic phosphorus was 0.876 of the value obtained when the material was analyzed by the reference method. Thus there is a significant systematic error in the SMAC method for inorganic phosphorus determination, attributable to an erroneous inorganic phosphorus concentration assigned the SMAC calibration material by the supplier (Technicon).

Autoanalysis↗

Computer analysis of Staphylococcus aureus phage typing data from 1957 to 1975, citing epidemiological trends and natural evolution within the phage typing system.

Computer analysis of Staphylococcus aureus phage ty ping data collected for over 18 years in a large research hospital showed a drastic decrease in the number of hospital epidemic strains. Phage lysis patterns gradually modified from those of earlier years and were a reflection of changes within the S. aureus reservoir, and not within the typing phages, since the typing phages were used from stable lyophilized stocks. There was increasing cross-lysis of S. aureus strains by phages of lytic groups I, II, and III, such that this grouping was no longer epidemiologically valid. A 61% increase in unique strains occurred from the period 1957 to 1975. Disappearance of the widely recognized epidemic strains was followed by a proliferation of unique strains with individual phage patterns. These increased from 38% in the period 1957 to 1962 to 62% in the period 1969 to 1975, indicating a trend toward a "one patient-one strain" situation. Nontypable strains decreased in more recent years from 16% (1957 to 1975) to 7% in 1978, following introduction of phages 94, 96, 292, and D-11. Pandemic S. aureus strain 80/81 first appeared in this hospital in 1959, 5 years after it was first reported in the United States. Strain 80/81 disappeared from the hospital in 1963, partly due to the advent of methicillin.

Bacteriophage Typing↗

Lot-to-lot variation in three thyroid-related radioimmunoassay kits.

We examined lot-to-lot variation in triiodothyronine, thyroxine, and thyrotropin radioimmunoassay kits over 14-20 months. For the thyroxine assay, less than 20% of the overall variation was attributable to lot-to-lot changes. In contrast, for the triiodothyronine and thyrotropin assays half to two-thirds of the overall variation was attributable to lot-to-lot differences. The shifts seen in control results were also observed in results for patients. These shifts produced disturbing deviations on quality-control charts but did not appear to compromise the clinical utility of the results. We conclude that lot-to-lot variation can account for a major part of the long term variability of radioimmunoassay kit results and should be considered in evaluating kits and monitoring their performance.

Humans↗

Biochemical individuality and the recognition of personal profiles with a computer.

Multitest analysis of an individual's blood provides a biochemical profile that reflects his identity and pathophysiological state. During a six-week period we repeatedly profiled 10 volunteers for 22 different analytes, using continuous-flow and discrete analyzers (SMAC, KA 150 enzyme analyzer, ABA-100, AutoAnalyzers) and manual procedures. Two years later, we obtained multiple follow-up profiles. Using linear discriminant functions derived from the first five (or first 10) specimens from each subject, we were able correctly to identify 96% (or 100%) of the specimens collected during the remainder of the six-week testing period. Ninety percent of the two-year follow-up specimens were correctly identified when we used all the original profiles to calculate the discriminant functions. Deliberately mislabeled specimens were also correctly identified by discriminant analysis. Profiles of individual samples (and average profiles for each subject) were graphically displayed as computer-drawn faces and non-linear maps. Covariances between pairs of tests on repeated profiles differed significantly for different subjects. Inter-test relationships were graphically displayed by nonlinear mapping.

Autoanalysis↗

Distribution of serum concentrations of creatine kinase MM and BB isoenzymes measured by radioimmunoassay.

Because of the recent interest in measuring serum enzyme concentration as opposed to catalytic activity, we measured the serum concentration of creatine kinase isoenzymes BB and MM by radioimmunoassay and the total creatine kinase enzymatic activity in healthy adults. For sex-race subgroups we report mean values and the 2.5, 5, 25, 50, 75, 90, 95 and 97.5 percentiles. Differences among average values of the subgroups were highly significant. Results within subgroups frequently departed from a gaussian distribution.

Black People↗

Is antiglycolysis required for routine glucose analysis?

We obtained -68 pairs of simultaneously drawn serum and fluoride-oxalate plasma samples from patients and analyzed them by a continuous-flow (AutoAnalyzer II) glucose oxidase method. Glucose concentrations ranged from 370 to 3530 mg/L. Glucose concentrations for samples obtained in the fluoride-oxalate preservative averaged 42 +/- 35 mg/L (mean +/- SD) higher than serum. The magnitude of this difference was independent of glucose concentration. Linear-regression analysis of 270 pairs for which the time from collection to separation was recorded indicated that the difference between serum and plasma increased by 0.32 mg/L per minute of delay over a time span of 15 to 295 min. These differences are smaller than those described in standard textbooks. We conclude that, with the specimen-handling process used in our hospital, serum glucose determinations are clinically acceptable.

Blood Chemical Analysis↗

Evaluation of a dispensing instrument (Dynatech MIC-2000) for preparing microtiter antibiotic plates and testing their potency during storage.

The MIC-2000 96-channel dispenser was evaluated for accuracy and repeatability of dispensing 50-mul volumes of water. It was found to perform within the manufacturer's specifications for accuracy of +/-5%, but not within the limits for repeatability of +/-1%. Overall, instrument performance was found to be satisfactory for the antimicrobial susceptibility testing technique which has been implemented in this laboratory. A method is suggested for simple evaluation of the volumes dispensed. A variety of antibiotics may be stored in Trypticase soy broth in Microtiter plates without loss of potency for periods of at least 2 weeks at -20 degrees C and 4 months at -70 degrees C.

Anti-Bacterial Agents↗