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R H Laessig

Publications and source records attributed to R H Laessig.

At least 19 recordsLinked to original sources
PubMed1992

Health Care Financing Administration's new proficiency testing rules. Use of a statistical approach to predict long-term performance using the categories 'successful,' 'probation,' and 'suspended'.

Under the Clinical Laboratory Improvement Act of 1967 (CLIA-67) and the Medicare Act, the Health Care Financing Administration's proficiency testing rules apply uniformly to all hospital and reference laboratories. We examined the relationship between internal laboratory performance as characterized by bias and coefficient of variation and proficiency testing performance, categorized as "successful," "probation," and "suspended." Under the March 14, 1990, final rule, a laboratory with suspended testing for even one analyte may be required to cease testing in the entire subspecialty, eg, routine chemistry, unless it ceases testing for that analyte. Analyzing this regimen as a Markov process, we obtained the steady-state solution for performance for one to 27 analytes. While 1.1% of laboratories testing for five analytes with internal or day-to-day coefficients of variation at 50% of the CLIA-67 proficiency testing limit would be suspended, 19.5% of laboratories having biases of 50% and coefficients of variation of 33% would be suspended. We conclude that after eight events, there will be an unacceptably high rate of suspensions.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed1992

The effect of dentures and denture adhesives on mouth alcohol retention.

A total of 24 alcohol-free, denture-wearing subjects were tested for mouth-alcohol retention times with an Intoxilyzer 5000. The subjects were given 30 mL doses of 80 proof brandy to swish in their mouths without swallowing for 2 min prior to expectorating the dose. Subjects were tested under three conditions: 1) with dentures removed, 2) with dentures held loosely in place without an adhesive, and 3) with dentures plus an adhesive. Beyond 20 min following expectoration, mouth alcohol made no significant contribution to the apparent breath alcohol concentration (BrAC), with trace (less than or equal to 0.01 g/210 L) readings found in only two of the subjects. Denture use, both with and without the concurrent use of adhesives does not significantly affect BrAC as long as a pretest alcohol deprivation period of 20 min is observed.

Adhesives↗
PubMed1992

Are clinical laboratory proficiency tests as good as they can be?

Present proficiency test services that use the peer group mean and statistically derived ranges of acceptability are not serving us optimally and are even counterproductive in some respects. We recommend that the target value be determined by a widely accepted reference method and that acceptable ranges be based on criteria related to clinical need. This approach was adopted several years ago in Germany and has already eliminated the use of several unsatisfactory analytical methods. Because the transition would probably take many years, we propose an interim solution to allow instrument manufacturers and laboratorians to adapt to these changes. The current peer group means and acceptable ranges should be supplemented by reference method values and acceptable ranges, based on clinical need, so that manufacturers and laboratorians can judge their performance against these new criteria and make the necessary adjustment in instrumentation and methodology. These processes should be paralleled by efforts to produce proficiency test materials that will not exhibit the matrix problems of present-day preparations.

Chemistry, Clinical↗
PubMed1992

Intralaboratory performance requirements necessary to pass proficiency testing: CAP-1990 vs CLIA-1967 (March 14, 1990) formats compared.

The pre-1990 College of American Pathologists' (CAP) Proficiency Testing (PT) program used a two samples per analyte/four challenges per year format with performance or pass-fail grading criteria determined by the program. On Jan. 1, 1991, the Clinical Laboratory Improvement Act of 1967 (CLIA-67) final rules (March 14, 1990) mandated a revised PT format of five samples per analyte/four challenges per year, with the regulations specifying minimum performance criteria. Extending our previous analysis, we compare the maximum permissible intralaboratory imprecision at low bias compatible with passing external PT in the former CAP and current CLIA-67 formats. If a laboratory is able to reduce its internal coefficient of variation (CV) to less than 44% of the PT criterion for each analyte, its overall chance of adverse action for any of the 27 routine chemistry analytes specified in CLIA-67 will be less than 1% in a two-year (eight PT challenges or events) period. Consideration of actual interlaboratory CVs from CAP surveys suggest that a reduction of this magnitude may be difficult for the analytes total cholesterol and blood urea nitrogen, where intralaboratory imprecision comparable with the group standard deviation (SD) from 1990 CAP surveys would yield individual adverse action (PT failure) rates of 5% and 1%, respectively. Five other analytes have CLIA-67 performance limits dangerously close to CAP interlaboratory CVs.

Chemistry, Clinical↗
PubMed1992

Limitations of proficiency testing under CLIA '67.

Proficiency testing (PT), recognized as a quality-assurance (QA) and quality-improvement tool, also has become the cornerstone of the Health Care Financing Administration's (HCFA) regulatory strategy under the revised Clinical Laboratory Improvement Act of 1967 (CLIA '67) and the proposed Clinical Laboratory Improvement Amendments of 1988 (CLIA '88). Use of PT as a regulatory tool corrupts it for things it can do better. PT as a primary regulatory strategy has severe limitations. We explore the nature of these limitations and their implications for clinical laboratories as they impact on the long-term success of HCFA's approved regulatory PT programs in 1991 and beyond, and CLIA '88 PT, which is to be implemented in 1994.

Chemistry, Clinical↗
PubMed1992

Review of actual proficiency-testing performance under CLIA '67 (March 14, 1990) rules: perspective from the first year's data.

Under the Clinical Laboratory Improvement Act of 1967 the Health Care Financing Administration's proficiency-testing requirement applies to approximately 12,000 hospital, reference, and large-clinic laboratories in the United States. The Wisconsin State Laboratory of Hygiene is approved by the Health Care Financing Administration to provide proficiency testing in all specialties and subspecialties. The focus of the program is to provide highly specialized service and support to a limited number of participants in order to assess intralaboratory performance correctly. We report the findings over the four proficiency-testing events in 1991 for the subspecialty of routine chemistry, which serves approximately 470 participants. Failure rates for individual analytes on single proficiency testing events ranged from 0% to 13%. After four events or one year, if the mandated evaluation criteria and failure rules were strictly applied, as many as 11% of the laboratories could have found themselves involuntarily suspended from offering all routine chemistry testing.

Chemistry, Clinical↗
PubMed1992

Comparison of plastic vs. glass evacuated serum-separator (SST) blood-drawing tubes for common clinical chemistry determinations.

We evaluated a plastic evacuated blood-drawing tube containing an integral serum-separating barrier gel, by direct comparison with a glass counterpart. The plastic tube demonstrated no differences when compared for common clinical chemistry analytes with multiple types of instruments and systems. A total of 260 such different combinations were studied with emphasis on tests sensitive to drawing and handling indexes such as lactate dehydrogenase and potassium. A total of six separate blood drawings were tested with no significant differences noted in these tests. The total study included subjective evaluations of the plastic tube's use as a blood-drawing device and objective studies based on quantitative test results from normal and hospitalized patients and use of the primary sampling tubes (both plastic and glass) for 48-h storage.

Blood Specimen Collection↗
PubMed1991

Current issues in neonatal screening for cystic fibrosis and implications of the CF gene discovery.

Many questions remain regarding the efficacy, toxicity, and costs of CF neonatal screening. It would be premature, in our opinion, to implement mass population screening of newborns for CF until the benefits and risks have been fully defined, and an adequate and logistically feasible testing system developed and/or highly effective therapy for CF lung disease becomes available. In addition, the ethical issues described herein need to be resolved. This pertains not only to the CF patient but also the heterozygote carrier. These reservations notwithstanding, the discovery of the CF gene should have a favorable impact both directly and indirectly on neonatal screening for the disease. Mutation analysis coupled to IRT testing seems most attractive at this time, at least on a research basis, but primary molecular diagnostic procedures might supervene in the future, particularly if they are financially feasible.

Chromosome Mapping↗
PubMed1991

Laboratory quality control issues related to screening newborns for cystic fibrosis using immunoreactive trypsin.

We have incorporated the IRT assay for CF to our newborn screening program, relying heavily on electronic data processing to optimize the test results in order to provide the most reliable data possible from the specimen at hand. We have established an internal cut-off of 100 ng/mL and an external referral of 180 ng/mL; this virtually eliminates the possibility that analytical imprecision will result in misidentifying a positive patient specimen. The relationship between IRT levels and various mutant forms of CF are not well established, and it is possible that various forms of CF may exhibit different levels of IRT in the first few days of life. We believe that IRT screening for CF could be a useful procedure for early identification of potential CF. However, by comparison with other newborn screening tests, its sensitivity, 90%, presents a concern. The expectation for PKU, hypothyroidism, MSUD, and galactosemia screening is 100% sensitivity. A false-negative usually results in litigation. The use of IRT in routine newborn screening will require considerable education of the general public and physicians receiving test results. Our program, along with many others, is anxiously watching the developments in the area of gene testing. We feel the relatively inexpensive IRT, used for mass screening can be successfully coupled with the more definitive (and expensive) gene test on a selected population to identify CF at the earliest possible age in a more effective manner. It is possible that in the near future gene probe tests will be applied in a cost effective manner to the initial filter paper specimen.

Cystic Fibrosis↗
PubMed1990

1990 Medicare/CLIA final rules for proficiency testing: minimum intralaboratory performance characteristics (CV and bias) needed to pass.

On March 14, 1990, the Centers for Disease Control and the Health Care Financing Administration published criteria for defining minimum performance in proficiency testing (PT). Using our previously described computer modeling technique, we determined the likelihood of passing PT under the new rules. The model relates combinations of intralaboratory CV and bias to PT performance criteria. For example, a laboratory with a bias of zero and an internal CV of 5% will pass a 10% fixed-limit PT criterion (i.e., the criterion for glucose analyses) 98% of the time when five samples are used. The model provides similar analyses for all PT criteria and all relevant combinations of CV and bias. The probability of passing PT decreases as the number of analytes tested increases, i.e., from 98% to 37% as the number of analytes increases from 1 to 20. A laboratory's internal CV has a greater effect on the outcome of PT than do the corresponding bias values. We conclude that a laboratory that operates with methods that have internal CVs less than or equal to 33% and biases less than or equal to 20% of the PT criteria will have a greater than 99% chance of passing PT.

Centers for Disease Control and Prevention, U.S.↗
PubMed1990

Newborn screening for cystic fibrosis is complicated by age-related decline in immunoreactive trypsinogen levels.

Detection of elevated levels of immunoreactive trypsinogen (IRT) in dried neonatal blood spots has been used as a screening test for cystic fibrosis. In other cystic fibrosis newborn-screening studies, a sweat chloride test is generally performed only if an infant has a persistent IRT level above a selected cutoff value on both the initial and subsequent specimens. Neither the timing of the second specimen nor the value of the cutoff point for the second specimen has been comprehensively evaluated. In this randomized, controlled study, 145,024 infants were screened in the neonatal period for cystic fibrosis using the 99.8 percentile (180 ng/mL) as the neonatal cutoff point. A total of 129 infants had elevated neonatal IRT levels and had negative results on sweat tests (false-positive by IRT screening). A total of 54 children with cystic fibrosis were identified in the screened and comparison groups. Excluding patients with meconium ileus, 4 infants with cystic fibrosis had neonatal IRT values less than 180 ng/mL, and an additional 9 infants with cystic fibrosis had values decline to less than 180 ng/mL within the first 2 1/2 months of age. The IRT values of infants with and without cystic fibrosis overlapped considerably beyond 30 days of age. These findings suggest that further refinement of cystic fibrosis screening methodology will be necessary to achieve an acceptable sensitivity and specificity.

Aging↗
PubMed1990

Field performance of the Intoxilyzer 5000: a comparison of blood- and breath-alcohol results in Wisconsin drivers.

Intoxilyzer 5000 and blood-alcohol results from drivers arrested for operating a motor vehicle while intoxicated and for related offenses were compared during a two-year period. Three hundred and ninety-five pairs of results were studied. The breath- and blood-alcohol specimens in this study were collected within 1 h of each other. The mean blood-alcohol concentration obtained was 0.180 g/dL, with a range from zero to 0.338 g/dL. By comparison, the mean Intoxilyzer 5000 result was 0.16 g/210 L with a range from zero to 0.32 g/210 L. Compared with the blood-alcohol result, Intoxilyzer 5000 results were lower by more than 0.01 g/210 L 67% of the time, within 0.01 g/210 L 31% of the time, and higher by more than 0.01 g/210 L 2% of the time.

Alcoholic Intoxication↗
PubMed1989

Immunoreactive trypsinogen screening for cystic fibrosis: characterization of infants with a false-positive screening test.

Blood immunoreactive trypsinogen (IRT) is elevated in newborns with cystic fibrosis (CF) and has been used as a neonatal screening test. However, not only is the benefit of early diagnosis unknown, but also the sensitivity, specificity, and time related decline of IRT values have yet to be comprehensively evaluated. This report describes the characteristics of infants with a false-positive IRT in our experience with CF screening of 87,000 infants. The IRT value was elevated in 92 newborns; 13 had a confirmed diagnosis of CF by quantitative pilocarpine iontophoresis sweat testing, and 79 infants did not have CF and were therefore classified as false positives by IRT screening. In order to test the hypothesis that perinatal stress factors are associated with high neonatal IRT values, we evaluated Apgar scores at 1 and 5 minutes. We found that the scores of false-positive infants were significantly lower (P = 0.0004 and P = 0.0102 at 1 and 5 minutes, respectively), compared with infants in the general population. While perinatal asphyxia as reflected by low Apgar scores is an associated factor accounting for an elevated IRT value, the majority of non-CF newborns with an elevated IRT have normal Apgar scores.

Apgar Score↗
PubMed1988

Testing cholesterol accuracy. Performance of several common laboratory instruments.

The national emphasis on assessing coronary risk by cholesterol testing mandates that analytical determinations be as accurate and precise as is medically necessary. One goal of the National Cholesterol Education Program is to improve the quality of laboratory tests. Currently, 5% limits of imprecision and 5% of bias vs the nationally accepted Abell-Kendall reference method is recommended, with a goal of reducing these limits to 3% by 1992. Clinicians must be aware of how the cholesterol values are obtained, and especially whether the laboratory's method meets the performance goals. We assayed patients' serum samples for cholesterol using several commercially available, routinely used enzymatic methods and by the Abell-Kendall reference method. Precision of these methods was also assessed using serum-based controls. All instruments were operated precisely according to the manufacturers' instructions. Performance was objectively judged based on the National Cholesterol Education Program goals and on medically allowable total error. In all cases, the DuPont aca, the Kodak Ektachem, the Hitachi 737, and the Cobas FARA determined cholesterol levels acceptably. The precision and accuracy goals of 3% are achievable by these methods.

Adult↗
PubMed1988

The relationship of intralaboratory bias and imprecision on laboratories' ability to meet medical usefulness limits.

The previously described computer modeling technic empirically develops quantitative relationships between intralaboratory performance, as characterized by individual laboratories' coefficients of variation (CVs) and biases, and clinical "medical usefulness limits." These limits determine the magnitude of total analytic error, the combined effects of CV and bias that can be tolerated by the clinician. The computer model delineates all combinations of CV and bias compatible with specified medical usefulness limits. Both CV and bias are critical in determining a laboratory's ability to meet medical usefulness limits. For example, a laboratory with a 6% CV and zero bias will meet the +/- 10% or less total analytic error (medical usefulness limit) 90% of the time. If the medical usefulness limit is expanded to +/- 15%, a laboratory with a 6% CV can tolerate coexisting relative biases of up to 4% and still meet this limit 95% of the time. Plots of the limiting values for combinations of intralaboratory CV and bias are given that allow the laboratory's results to fall within medical usefulness limits of 2, 5, 10, 15, and 20%.

Clinical Laboratory Techniques↗
PubMed1988

Use of computer modeling to predict the magnitude of intralaboratory error tolerated by proposed CDC interlaboratory proficiency testing performance criteria.

In December 1987, the Centers for Disease Control (CDC) proposed to the Health Care Financing Administration revised criteria for evaluating participating laboratories' performance in proficiency-testing programs. If these criteria are accepted, they will become the minimum standard for all regulatory proficiency-testing programs. To evaluate a laboratory's performance in a clinical chemistry proficiency-testing program, the CDC proposed a combination of the use of fixed limits, multiples of the interlaboratory group standard deviations, and absolute values. In addition, laboratories would be required to meet 70% of the most recent proficiency-testing challenges. Because the purpose of regulatory proficiency testing is to identify poorly performing laboratories, it is essential that regulators be aware of the relationship between the regulatory criteria and the actual magnitude of intralaboratory error they tolerate. Through computer simulation, we determined for 21 chemistry analytes the amount of intralaboratory error tolerated by the CDC-proposed criteria. We evaluated the effectiveness of the proposed criteria by comparing the levels of total intralaboratory error permitted by a proficiency-testing program by using the CDC criteria with actual currently achievable levels of performance and defined medical usefulness needs. The proposed CDC criteria were too lenient for six analytes, about correct for seven, and too stringent on two; no medical usefulness limits were available for six.

Blood Chemical Analysis↗
PubMed1988

Use of alternative rules (other than the 1(2)s) for evaluating interlaboratory performance data.

Previous studies have documented the ineffectiveness of using either the group mean +/- 2 group standard deviations (SD) or the 1(2)s rule as the standard of acceptable performance in evaluating interlaboratory proficiency testing (PT) data. Using computer simulation of PT data, we evaluated the efficiency of 244 alternatives to the 1(2)s rule, all based on the PT population's mean and SD. Using the traditional interlaboratory PT format, we determined the ability of each rule to correctly identify both good and deficient intralaboratory performance. The rules are based on results from one to five PT samples "analyzed" at the same time. Because the effectiveness of the criteria set for acceptable performance in a PT program is influenced by the population SD, each rule's capabilities were examined for PT populations with interlaboratory SDs ranging from 1% through 10% of the population mean value. All rules achieve their maximum efficiency over a narrow range of interlaboratory SDs. For PT evaluations of intralaboratory performance to be optimally effective, selection of the rule must be based on the SD of the PT population.

Computers↗