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Biomedical subjects

R W Jenny

Publications and source records attributed to R W Jenny.

10 recordsLinked to original sources
PubMed2000

Causes of unsatisfactory performance in proficiency testing.

BACKGROUND: Proficiency testing (PT) provides a measure of the effectiveness of laboratory quality assurance programs. Test reports are released from processes that the laboratory judges to be in conformance with quality specifications; an evaluation of unsatisfactory performance (UNSAT) by a PT provider is an unexpected outcome for the laboratory. An understanding of the root cause(s) of testing errors provides an opportunity for the continuous improvement of laboratory services. METHODS: We used participant data from the New York State Department of Health PT program to characterize the quality of testing in the toxicology specialty. Outcomes from laboratory investigations into causes of UNSAT and information on quality control practices collected from all program participants were used to identify the root causes of error. RESULTS: Two classes of error were encountered: spurious test results caused by lapses in standard operating procedures and instrument malfunctions (300 per million assays) and common-cause analytic error (7000 per million assays or 0.7% rate of UNSAT). Causes of spurious results included inaccurate mathematical correction for specimen dilution, misinterpretation of instrument codes, and instrument sampling errors. Calibration drift was most frequently cited as the common-cause analytic error. Approximately one-half of the laboratories used an allowable error for the quality control of analytical systems that exceeded the threshold error specified by manufacturers for stable instrument performance. CONCLUSIONS: The causes of spurious results suggest the need for ongoing competency testing of analysts where analyst intervention is required in an otherwise automated process, and for continued diligence in mistake-proofing instrument design. The intrinsic quality of laboratory testing is unlikely to improve until the allowable error in quality control is consistent with manufacturer specifications for stable system performance.

Clinical Chemistry Tests↗
PubMed1997

Clinical significance of methohexital, meperidine, and diazepam in breast milk.

Concentrations in breast milk of medications used during general anesthesia were measured to determine whether interruption of breast-feeding was indicated. Breast milk and maternal blood samples were obtained from nine women undergoing tubal sterilization under general anesthesia. Concentrations of methohexital, meperidine, diazepam, and nordiazepam were determined for each sample by gas chromatography. Methohexital levels declined rapidly after the first hour and were undetectable at 24 hours. Meperidine was present in both milk and blood during the recovery period but not at 24 hours. Infant-exposure indices for methohexital were less than 1% and ranged from 1.2% to 3.5% for meperidine. The maximum doses of methohexital and meperidine to an infant, in a 100 mL feeding 1 hour after induction of anesthesia were estimated to be 0.04 mg and 0.06 mg, respectively. Diazepam and nordiazepam were not detectable in any sample of milk or blood. The maximum possible infant-exposure index for diazepam would be 3%. The amounts of methohexital, meperidine and diazepam excreted into breast milk do not warrant interruption of breast-feeding.

Adult↗
PubMed1994

Process capability and stability of analytical systems assessed from proficiency testing data.

Participation in a proficiency testing (PT) program is a valuable adjunct to laboratory activities dedicated to the maintenance of reliable analytical methods. The PT program may facilitate continuous quality improvement if laboratory performance is presented in the context of expectations espoused by healthcare professionals for optimal patient care. Statistical process control (SPC) and capability analysis are tools used by industry in a Total Quality Management environment to characterize and monitor the performance of its processes relative to performance specifications. I conceptualized the use of an analytical system by many laboratories as a process that periodically produces results from the analysis of PT specimens. I treated a set of five PT results (theophylline) reported by a laboratory as a process sample and subjected the samples collected from many laboratories to SPC and capability analysis. The control charts--mean-(X-bar) and s-charts--produced by the analysis readily identify significant analytical errors in the context of peer performance and performance specifications provided by the regulatory program and analytical goal setting. The capability index (desirable Cp > 1.0) determined from clinical specification limits for the three analytical systems evaluated suggests an opportunity for improvement of laboratory performance.

Chemistry, Clinical↗
PubMed1993

Proficiency test performance as a predictor of accuracy of routine patient testing for theophylline.

Proficiency testing (PT) is pivotal in assessing laboratory qualifications for certification and licensure. PT is expected to typify routine assay performance and determine whether the laboratory is producing clinically useful test results. Conventional schemes use mail-distributed test specimens and are often criticized as measuring the best possible laboratory performance, principally because of special practices associated with processing PT specimens. We used on-site proficiency tests and split samples to evaluate the ability of conventional PT schemes to accurately characterize routine laboratory performance. Using 412 assays of theophylline, performed routinely by 200 laboratories and subsequently in a reference laboratory, we found that the predictive value of PT performance in assessing quality of routine testing was high (100% for predicting substandard reliability of routine patient testing and 94% for excluding substandard reliability of patient testing). The imprecision of interlaboratory PT results was equivalent whether testing was observed (hand-carried specimens) or unobserved (mail-distributed specimens). Many methods used for determining theophylline concentration in serum were highly automated, closed, and precise analytical systems. The performance characteristics of these analytical systems are not easily manipulated by the analyst for purposes of improving PT outcome, and PT by use of mail-distributed test specimens is effective for assessing intralaboratory performance.

Chemistry, Clinical↗
PubMed1992

Evaluation of the rigor and appropriateness of CLIA '88 toxicology proficiency testing standards.

The proposed rule for the Clinical Laboratory Improvement Amendments of 1988 (CLIA '88) describes uniform standards for the design of proficiency testing (PT) challenges and for the evaluation of laboratory performance. Successful performance on PT is a condition for laboratory certification by the federal Department of Health and Human Services. We conducted a retrospective evaluation of PT data collected from laboratories participating in the New York State therapeutic substance monitoring/quantitative toxicology PT program to determine how well laboratories performed by proposed PT standards. We found that the unsuccessful performance rate is very low (less than 0.4%) and that laboratories providing limited services are more susceptible to program sanctions than are full-service laboratories. The performance criteria are empirically fixed limits that are not consistent with either the state of practice or the analytical goals based on clinical requirements for good patient care. We suggest that the performance standards, if adopted, would be a weak challenge to the capability of today's therapeutic drug monitoring service and will not provide the impetus to bring analytical performance characteristics into full compliance with analytical goals.

Laboratories↗
PubMed1992

How good are clinical laboratories? An assessment of current performance.

The Clinical Laboratory Improvement Act of 1967 and Amendments of 1988 (CLIA '67 and CLIA '88) were enacted to ensure that clinical laboratories within the U.S. provide a quality of service that meets clinical needs for good patient care. Approved proficiency-testing programs are to judge the quality of laboratory testing by promulgated performance criteria. We examine the quality of analytical results reported in 1991 to the New York State Department of Health Proficiency Testing program in light of these criteria and analytical goals, based on medical usefulness. Analytical performance is examined for cholesterol, potassium, sodium, calcium, glucose, aspartate aminotransferase, digoxin, and theophylline. In general, proposed CLIA '88 performance standards are compatible with the current state of practice for the population of laboratories examined. Exceptions appear to be digoxin and sodium (failure rate exceeding average) and most therapeutic substances (low failure rate). Sources of analytical bias relative to an accuracy-based target value must be characterized as method-, laboratory-, or matrix-dependent if regulatory programs are to achieve the objective of improving analytical accuracy across all testing sites.

Chemistry, Clinical↗
PubMed1991

Analytical goals for determinations of theophylline concentration in serum.

Statistical principles for analytical goal-setting were applied to two medical applications of drug-monitoring data: (a) individualizing dosage requirements by reference to a population-based therapeutic range or to a patient-specific decision value determined by Bayesian decision analysis, and (b) prospective dosing by using pharmaco-kinetic principles. For application a, the analytical goal for total allowable analytical error (TE) was defined as the amount of error that does not decrease by more than 5% either the sensitivity (probability) for detecting dosage regimens that may require modification or the specificity for detecting appropriately dosed patients. The limiting factor in achievable sensitivity and specificity was the intra-individual variation of peak steady-state concentration (Css), with the TE determined to be a CV of 4%. For application b, error-propagation rules were applied to a proposed prospective dosing scheme (J Pharmacokinet Biopharm 1978;6:135-51). The TE was determined to depend on the rate of theophylline clearance. For clearance rates less than or equal to 0.6 mL/(kg.min), the TE (CV) must not exceed 3% if the predicted infusion rate is to produce, with 95% confidence, a concentration within the therapeutic range.

Humans↗
PubMed1985

Interlaboratory evaluation of salicylate interference in colorimetric acetaminophen methods and its clinical significance.

Serum specimens with concentrations simulating an overdose of salicylate and acetaminophen were submitted to laboratories participating in an external quality-control program, to evaluate both the magnitude of salicylate interference in colorimetric acetaminophen methods and the clinical significance of the interference. The apparent acetaminophen concentration determined by nitration methods was increased by about 0.70 mg/L per milligram of salicylate per deciliter. Of those laboratories using nitration procedures, 25% do not routinely correct for salicylate and 66% use the (incorrect) correction factor provided by a kit manufacturer. Laboratory data, as they would have been reported to physicians, were used to estimate the acetaminophen half-life and were also applied to a nomogram used to assess the probability of hepatotoxicity. Interference by salicylate in the simulated overdose of 10 g (total dose) of each drug falsely indicated impending hepatic necrosis unless the appropriate correction factor was used. Laboratories using nitration procedures should screen samples submitted for acetaminophen assay for the presence of salicylate and, if present, either use a method specific for acetaminophen or utilize a correction factor determined in-house.

Acetaminophen↗
PubMed1981

Measurement of alkaline phosphatase activity: characterization and identification of an inactivator in 2-amino-2-methyl-1-propanol.

An inactivator of alkaline phosphatase (EC 3.1.3.1) in 2-amino-2-methyl-1-propanol is demonstrated and characterized. This time-dependent inactivation results from chelation of enzyme-bound Zn2+; it is reversed by addition of Zn2+ and, to a lesser extent, other divalent metal ions. Cu2+ is an effective spectral indicator and can be used to determine the presence and quantity of inactivator. Data obtained from enzyme inactivation, Cu2+ absorbance spectra, "high-performance" liquid chromatography, thin-layer chromatography, Fourier-transform infrared spectroscopy, and mass spectroscopy indicate that the inactivator is 5-amino-3-aza-2,2,5-trimethylhexanol. This compound, even in trace amounts (less than 0.05% on a molar basis), shown to inactivate alkaline phosphatase.

Alkaline Phosphatase↗