Biomedical subjects
J T Barr
Publications and source records attributed to J T Barr.
Using population-based serum drug concentration cutoff values to predict toxicity: test performance and limitations compared with Bayesian interpretation.
The use of population-based serum drug concentration cutoff values for several commonly monitored drugs as tests to distinguish toxicity from nontoxicity was studied. Serum drug concentration and response data published in studies of theophylline, digoxin, aminoglycosides, vancomycin, and procainamide were analyzed to determine the prevalence of toxicity in each group of patients. Serum drug concentration cutoff values were then varied, and the following performance characteristics of the cutoffs as tests for predicting toxicity were calculated for each value: sensitivity, specificity, likelihood ratio, predictive value, and ratio of net consequences. At commonly accepted cutoff values, sensitivity was lower than desirable, positive predictive values were less than negative values, and the ratio of net consequences indicated that false-negative errors are implicitly weighted as more risky than false-positive errors. As the cutoff for each drug was increased, specificity increased but sensitivity decreased, positive predictive values increased but negative predictive values decreased, and the ratio of net consequences increased. Therapeutic drug monitoring would improve if practitioners and laboratorians collaborated to (1) conduct prospective studies of the test performance characteristics of drug concentrations, (2) estimate the pretest probability of toxicity for each patient, (3) combine the pretest estimate with the test characteristics to make a posttest estimate, and (4) develop a more patient-specific, Bayesian approach.
Protein and elemental analysis of contact lenses of patients with superior limbic keratoconjunctivitis or giant papillary conjunctivitis.
Soft contact lenses worn by six patients (12 eyes) diagnosed as having contact lens-induced superior limbic keratoconjunctivitis (SLK) and from four patients (5 eyes) with giant papillary conjunctivitis (GPC) were analyzed for protein concentration and for elemental content. Fifty-five percent water content, ionic lenses containing methacrylic acid had high protein concentration. Calcium was not a common element found on protein-coated lenses. Sulfur and iron were found on used and new lenses. An elevated level of mercury was detected in one gray lens that had been disinfected in thimerosal-preserved saline with a high heat disinfection unit by a patient with SLK.
Making serum drug levels more meaningful.
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Increasing severity of illness among patients undergoing phase 1 trials. Implications for nursing resources.
To determine whether the severity of illness of hospitalized patients participating in Phase 1 trials has changed, a modified APACHE II (MA II) index was used to evaluate retrospectively each Phase 1 patient admitted during September through December 1983 and the same 4-month span in 1987. During the 1983 period, 28 patients were enrolled in 13 Phase 1 protocols. Their average length of stay (LOS) was 12.6 days (+/- 12.3 SD) with a mean MA II of 3.44 (+/- 2.69 SD). During the same 4 months in 1987, there were 37 patients enrolled in 18 Phase 1 trials with a mean LOS of 13.5 days (+/- 13.4 SD) and a mean MA II of 6.08 (+/- 3.33). As indicated by MA II scores, 1987 hospitalized patients enrolled in Phase 1 trials had a higher severity of illness than did 1983 Phase 1 patients (p = 0.01). The implications of an oncology patient population with an increasing severity of illness are examined in relation to nursing staff forecasting, resource allocation, and productivity.
Aspheric rigid gas permeable contact lenses: practitioner discrimination of base curve increments using fluorescein pattern evaluation.
Evaluation of the fluorescein pattern is the main clinical indicator of the fit of a rigid gas permeable (RGP) contact lens to the cornea. Traditionally, manufacturers inventory RGP lenses in 0.05-mm base curve increments. The objective of this study was to test the hypothesis that experienced practitioners are not able to discern base curve/cornea relations of aspheric design lenses correctly to within +/- 0.05 mm. Eleven clinicians with expertise in fitting rigid lenses were asked to interpret fluorescein patterns and lens fittings of the Bausch & Lomb Quantum aspheric RGP lens on five adapted rigid lens wearers. The results showed that the experienced practitioners used in this study were not able to discriminate cornea/base curve relations of Quantum aspheric lenses within +/- 0.05 mm more than 67% of the time (p less than 0.05). There were no patient-to-patient differences based on type of lens fit (interpalpebral or lid attachment) or degree of corneal toricity. Lenses fitted in 0.10-mm base curve steps were judged as being as acceptable as lenses fitted in 0.05 mm steps (p less than 0.05). It was concluded that Quantum aspheric design lenses need only be trial fitted in 0.10-mm base curve steps.
Evaluation of contact lenses by microbial enumeration and protein determination.
Contact lenses worn for varying periods of time (from 1 to 48 months) were subjected to microbiological examination by plate counts and protein determination. Seventy percent of the lenses displayed bacterial colony counts below 120 colony-forming units (CFU)/lens, 28 percent were in the range of 140 to 9060 CFU/lens, and one lens was contaminated with greater than 6 x 10(4) CFU/lens. Fungal contaminants were detected in three lens specimens in the range of 220 to 760 CFU/lens. Protein accumulation showed wide variation of up to 1.2 mg of protein per lens. Statistical analysis indicated highly significant associations (p less than 0.001) between the bacterial colony counts obtained with three different media. Some significant associations were found between the protein concentration and bacterial counts. The data did not indicate statistically significant relations between the above variables and either the water content or the length of wear of the contact lenses.
Design and interpretation of bioassays for carcinogenicity.
A description is presented of the difficulties often met in developing meaningful scientific discussions regarding regulatory policy, with examples. In particular, the design and interpretation of rodent bioassays evoke strong emotional responses in many areas. It is suggested that interested parties engage in a scientific debate on some of the more important issues in the appropriate journals, with the purpose of seeking consensus whenever that may be found.
Rodent carcinogenicity testing.
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Applying decision analysis in therapeutic drug monitoring: using receiver-operating characteristic curves in comparative evaluations.
In the first of a three-part series, decision-analysis techniques were applied to the evaluation, comparison, and selection of analytic systems for the purpose of improving the information content of serum drug concentration determinations. Receiver-operating characteristic (ROC) curves that graphically compare true-positive and false-positive rates at selected drug concentrations were developed and used to evaluate the clinical performance of analytic systems. Decision matrices were constructed using simulated toxicity and serum-concentration data from 150 subjects. These decision matrices were used to construct ROC curves and the curves were compared with prototype curves representing ideal, useful, useless, and hazardous test systems. The ROC curves were used to determine the analytic method (e.g., enzyme-multiplied immunoassay technique versus nephelometric assay) and analyte (e.g., free versus total drug concentration) that conveyed the most information and yielded the fewest errors in classifying patients as toxic or nontoxic. The use of ROC curves to compare new or modified analytic test systems, to monitor use of a given analytic method within an institution over time, and to compare the clinical performance of a given assay method in the therapeutic drug monitoring practices of various institutions is discussed. Decision-analysis techniques can assist practitioners in selecting the optimal analytic test system for reducing analytic variation as well as improving the quality and predictive ability of the serum drug concentration.
Applying decision analysis in therapeutic drug monitoring: using decision trees to interpret serum theophylline concentrations.
In the second of a three-part series, decision analysis is applied to therapeutic drug monitoring decisions that affect individual patients, using theophylline concentration and toxicity data to illustrate general concepts. Likelihood ratios and conditional probability curves were developed. The curves were used to determine the probability of toxicity based on the clinician's assessment of patient status and a measured serum theophylline concentration. A decision tree to "rule in" or "rule out" toxicity was constructed. Selection of a serum concentration cutoff level for classifying patients as toxic or nontoxic depends on the probabilities of the possible outcomes of the decision process and the clinician's assessment of the value of each possible outcome; therefore, no single concentration value is best for classifying patients. A decision tree was also constructed for evaluating therapeutic options when the clinician is confronted with adverse effects that may be drug related. In three prototype cases, the expected utility for discontinuing theophylline, continuing the drug at the same dosage, or lowering the dosage was determined and used to evaluate the relative worth of each therapeutic option. A more comprehensive interpretation of the serum theophylline concentration is provided by decision-analysis techniques than by observation of pharmacologic effect alone, because other factors such as merit, risk, and consequences of alternative decisions are considered.
The calculation and use of carcinogenic potency: a review.
Six methods of estimating carcinogenic potency now in use to some extent by regulatory agencies are examined. It is concluded that none of these methods is adequate for regulatory decision making when used alone, as is usually the case, but that all are useful as a contribution to the whole risk assessment process. The needs for further development and improvement of these methods, where appropriate to human risk, are identified and discussed in view of the growing use of potency estimates in regulatory decision making.
Comparing nonphysician and physician laboratory administrative responsibilities.
When the ASMT Board of Directors approved the conduct of a new laboratory management survey, they believed that the data from the survey would have value to the Society and its constituents. Indeed, it did. These data illustrated to federal health policy makers just how much of a role nonphysician clinical laboratory practitioners play in laboratory administration and day-to-day management. The results of this survey were extremely valuable to ASMT during recent federal regulatory and legal proceedings regarding the role of clinical laboratory scientists in laboratory services delivery and medicare payment policy for hospital clinical laboratory services.
A priori considerations when using laboratory determinations in cost-effectiveness and clinical decision analyses.
The incorporation of laboratory determinations into cost-effectiveness and clinical decision analyses can be weakened by failure to consider various sources of error in the generation and utilization of laboratory data. To improve these analyses, three phases in the process that converts a patient specimen into patient treatment are identified. Phase I examines quality of methodology and laboratory performance and identifies possible errors in generation of the analyte value. Phase II considers the process by which this value is compared to normal values; possible errors involved in normal value selection and the problem of false positives and false negatives are discussed. Phase III involves the interpretation of the values; possible errors in this phase are discussed. Recommendations are made to explicitly identify sources of error in all phases and thus strengthen decision analysis involving laboratory data.
Flatter than "K," on "K," steeper than "K": does the cornea know the difference?
Twenty-nine subjects were fitted with PMMA contact lenses of equal overall diameter, optical zone diameter, and z-value in a double-masked clinical trial. Five different treatment groups were analyzed and a one-way analysis of variance was used to determine whether significant differences in corneal thickness change existed between the treatment groups. Lenses fitted 1 D flatter than "K" caused the least amount of corneal thickness change.
Academic affiliation of medical laboratory science and pharmacy programs: Advantages for growth and recognition.
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Corneal endothelial observation techniques.
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Corneal endothelial response to rigid contact lenses.
Through modifications of the Nikon slitlamp, a system for repeatable central corneal endothelial photography was devised using the Holden-Zantos technique. The time course of the endothelial bleb response was charted for rigid contact lens wear and was found to reach a maximum at 10 to 50 min after lens insertion in the unadapted eye.