Laboratory assay reproducibility of serum estrogens in umbilical cord blood samples.
We evaluated the reproducibility of laboratory assays for umbilical cord blood estrogen levels and its implications on sample size estimation. Specifically, we examined correlation between duplicate measurements of the same blood samples and estimated the relative contribution of variability due to study subject and assay batch to the overall variation in measured hormone levels. Cord blood was collected from a total of 25 female babies (15 Caucasian and 10 Chinese-American) from full-term deliveries at two study sites between March and December 1997. Two serum aliquots per blood sample were assayed, either at the same time or 4 months apart, for estrone, total estradiol, weakly bound estradiol, and sex hormone-binding globulin (SHBG). Correlation coefficients (Pearson's r) between duplicate measurements were calculated. We also estimated the components of variance for each hormone or protein associated with variation among subjects and variation between assay batches. Pearson's correlation coefficients were >0.90 for all of the compounds except for total estradiol when all of the subjects were included. The intraclass correlation coefficient, defined as a proportion of the total variance due to between-subject variation, for estrone, total estradiol, weakly bound estradiol, and SHBG were 92, 80, 85, and 97%, respectively. The magnitude of measurement error found in this study would increase the sample size required for detecting a difference between two populations for total estradiol and SHBG by 25 and 3%, respectively. (+info)
Comparison of European and North American malignant hyperthermia diagnostic protocol outcomes for use in genetic studies.
BACKGROUND: Halothane and caffeine diagnostic protocols and an experimental ryanodine test from the North American Malignant Hyperthermia (MH) Group (NAMHG) and the European MH Group (EMHG) have not been compared in the same persons until now. METHODS: The outcomes of the NAMHG and EMHG halothane and caffeine contracture tests were compared in 84 persons referred for diagnostic testing. In addition, the authors assessed the experimental ryanodine protocol in 50 of these persons. RESULTS: Although the NAMHG and EMHG halothane protocols are slightly different methodologically, each yielded outcomes in close (84-100%) agreement with diagnoses made by the other protocol. Excluding 23 persons judged to be equivocal (marginally positive responders) by the EMHG protocol resulted in fewer persons classified as normal and MH susceptible (42 and 19, respectively) than those classified by the NAMHG protocol (48 and 34, respectively). For the 61 persons not excluded as equivocal, the diagnoses were identical by both protocols, with the exception of one person who was diagnosed as MH susceptible by the NAMHG protocol and as "normal" by the EMHG protocol. The NAMHG protocol produced only two equivocal diagnoses. Therefore, a normal or MH diagnosis by the NAMHG protocol was frequently associated with an equivocal diagnosis by the EMHG protocol. The time to 0.2-g contracture after the addition of 1 microM ryanodine completely separated populations, which was in agreement with the EMHG protocol and, except for one person, with the NAMHG protocol. CONCLUSIONS: Overall, the NAMHG and EMHG protocols and the experimental ryanodine test yielded similar diagnoses. The EMHG protocol reduced the number of marginal responders in the final analysis, which may make the remaining diagnoses slightly more accurate for use in genetic studies. (+info)
European interlaboratory comparison of breath 13CO2 analysis.
The BIOMED I programme Stable Isotopes in Gastroenterology and Nutrition (SIGN) has focused upon evaluation and standardisation of stable isotope breath tests using 13C labelled substrates. The programme dealt with comparison of 13C substrates, test meals, test conditions, analysis techniques, and calculation procedures. Analytical techniques applied for 13CO2 analysis were evaluated by taking an inventory of instrumentation, calibration protocols, and analysis procedures. Two ring tests were initiated measuring 13C abundances of carbonate materials. Evaluating the data it was found that seven different models of isotope ratio mass spectrometers (IRMS) were used by the participants applying both the dual inlet system and the continuous flow configuration. Eight different brands of certified 13C reference materials were used with a 13C abundance varying from delta 13CPDB -37.2 to +2.0/1000. CO2 was liberated from certified material by three techniques and different working standards were used varying from -47.4 to +0.4/1000 in their delta 13CPDB value. The standard deviations (SDs) found for all measurements by all participants were 0.25/1000 and 0.50/1000 for two carbonates used in the ring tests. The individual variation for the single participants varied from 0.02 /1000 (dual inlet system) to 0.14/1000 (continuous flow system). The measurement of the difference between two carbonates showed a SD of 0.33/1000 calculated for all participants. Internal precision of IRMS as indicated by the specifications of the different instrument suppliers is < 0.3/1000 for continuous flow systems. In this respect it can be concluded that all participants are working well within the instrument specifications even including sample preparation. Increased overall interlaboratory variation is therefore likely to be due to non-instrumental conditions. It is possible that consistent differences in sample handling leading to isotope fractionation are the causes for interlaboratory variation. Breath analysis does not require sample preparation. As such, interlaboratory variation will be less than observed for the carbonate samples and within the range indicated as internal precision for continuous flow instruments. From this it is concluded that pure analytical interlaboratory variation is acceptable despite the many differences in instrumentation and analytical protocols. Coordinated metabolic studies appear possible, in which different European laboratories perform 13CO2 analysis. Evaluation of compatibility of the analytical systems remains advisable, however. (+info)
Effects of a computerised protocol management system on ordering of clinical tests.
OBJECTIVE: To assess the effects of a computerised protocol management system on the number, cost, and appropriateness of laboratory investigations requested. DESIGN: A before and after intervention. SETTING: A supraregional liver unit in a teaching hospital. PATIENTS: 1487 consecutive patients admitted during 1990 and 1991 (one year before and one year after introduction of the system). INTERVENTION: Introduction of a computerised protocol management system on 1 January 1991. MAIN MEASURES: The number and cost of clinical chemistry tests requested per patient day. RESULTS: The total number of clinical chemistry tests requested per patient day by the unit declined 17% (p < 0.001, Student's t test) and of out of hours tests requested per patient day from 0.31 to 0.16, 48% (p < 0.001; Mann-Whitney U test), resulting in a 28% reduction (p < 0.001) in direct laboratory expenditure per patient-day. Overall, the number of tests per admission decreased by 24% (p < 0.001; Mann-Whitney U test). CONCLUSION: Use of the computerised protocol management system resulted in closer compliance with the protocols and a significant reduction in the overall level of requesting. IMPLICATIONS: Although similar systems need to be tested in other clinical settings, computerised protocol management systems may be important in providing appropriate and cost effective health care. (+info)
The diagnosis, classification, and management of asthma according to severity.
This activity is designed for primary care and specialist physicians. GOAL: To provide prompt and appropriate treatment for asthma of all levels of severity resulting in improved level of activity and decreased need for urgent care and hospitalization with a possible reduction in the annual decline of lung function, degree of permanent airway damage, and mortality. OBJECTIVES: 1. To provide a framework on the basis of history, physical findings, and laboratory results for the diagnosis of asthma. 2. To improve the ability to classify asthma by degree of severity. 3. To describe an incremental therapeutic approach to asthma by degree of severity. 4. To provide a systematic approach with regard to periodic reevaluation of asthma severity and modification of the treatment plan. (+info)
A cost/efficacy analysis of oral antifungals indicated for the treatment of onychomycosis: griseofulvin, itraconazole, and terbinafine.
This analysis was conducted at HIP Health plan of New Jersey (a Northeastern group model health maintenance organization) to determine the most cost-effective therapy among the three currently available oral antifungal drugs that are indicated for the treatment of onychomycosis: griseofulvin, itraconazole, and terbinafine. Costs of an appropriate and complete treatment regimen were calculated for each of the three drugs based on average wholesale price. Efficacy was determined by meta-analysis of the published literature for those studies where appropriate treatment regimens for onychomycosis were put to use. Efficacy outcome measures were limited to mycologic cure rates in the more recalcitrant cases of toenail onychomycosis. From these measures of cost and efficacy, a cost/efficacy ratio was calculated for each drug by dividing the cost per treatment by the weighted average mycological cure rate. This ratio represents the cost per mycologically cured infection. The final outcome measure (the cost per mycologically cured infection) was $2,721.28, $1,845.05, and $648.96, for griseofulvin, itraconazole, and terbinafine continuous therapies, respectively. For itraconazole and terbinafine pulse therapy, the costs were $855.88 and $388.50, respectively. For both continuous and pulse therapy, terbinafine is apparently the most cost-effective drug, followed by itraconazole and then by griseofulvin. Terbinafine has the fewest drug interactions and the highest treatment success rate. (+info)
Affinity chromatography: a review of clinical applications.
Affinity chromatography is a type of liquid chromatography that makes use of biological-like interactions for the separation and specific analysis of sample components. This review describes the basic principles of affinity chromatography and examines its use in the testing of clinical samples, with an emphasis on HPLC-based methods. Some traditional applications of this approach include the use of boronate, lectin, protein A or protein G, and immunoaffinity supports for the direct quantification of solutes. Newer techniques that use antibody-based columns for on- or off-line sample extraction are examined in detail, as are methods that use affinity chromatography in combination with other analytical methods, such as reversed-phase liquid chromatography, gas chromatography, and capillary electrophoresis. Indirect analyte detection methods are also described in which immunoaffinity chromatography is used to perform flow-based immunoassays. Other applications that are reviewed include affinity-based chiral separations and the use of affinity chromatography for the study of drug or hormone interactions with binding proteins. Some areas of possible future developments are then considered, such as tandem affinity methods and the use of synthetic dyes, immobilized metal ions, molecular imprints, or aptamers as affinity ligands for clinical analytes. (+info)
Genetic testing and the clinical laboratory improvement amendments of 1988: present and future.
CLIA '88 superseded CLIA '67. CLIA '88 set standards designed to improve quality and expanded federal oversight to virtually all clinical laboratories in the United States. Presumably because genetics testing was then in its infancy, CLIA '88 did not devote a special section to genetics testing. Biochemical and immunochemical tests used to evaluate inborn errors of metabolism and other genetic entities were categorized as analytes in the Clinical Chemistry section, and DNA probes used primarily in infectious disease were included in Microbiology. The legal, social, economic, and ethical implications of genetic testing and the rapid commercialization of these tests led to recommendations that genetic testing be defined as a laboratory specialty with a subsection in CLIA. The advisory committee created under CLIA was assigned to review these recommendations. The committee agreed that genetics testing was sufficiently different from other areas already included in CLIA to warrant a separate section. Two definitions were adopted. The more clear-cut one is for molecular genetic and cytogenic tests. This includes the analysis of human DNA/RNA in evaluating genetic diseases. The second definition is not as clear-cut and is for the analysis of proteins and metabolites used predominantly to detect inborn errors of metabolism. Many of these analytes already are categorized according to their uses for other purposes. The recommendations for genetic testing include detailed and specific proposals concerning personnel, confidentiality and informed consent, quality control, contamination, proficiency testing, validation of tests, special reporting, retention of records, and reuse of tested specimens. (+info)