Clinical efficacy of three assays for cardiac troponin I for risk stratification in acute coronary syndromes: a Thrombolysis In Myocardial Infarction (TIMI) 11B Substudy.

BACKGROUND: Significant analytic variability exists between the multiple assays for cardiac troponin I (cTnI) approved for clinical use. Until adequate cTnI standardization is possible, an evidence-based approach evaluating each assay at specific thresholds appears warranted. METHODS: We examined the efficacy of three cTnI assays for predicting death, myocardial infarction (MI), or the composite of death, MI, or urgent revascularization at 43 days among patients with non-ST-elevation acute coronary syndromes enrolled in the Thrombolysis In Myocardial Infarction (TIMI) 11B study. RESULTS: Six hundred eighty-one patients with serum samples obtained at baseline and/or 12-24 h had cTnI determined using all three assays. Baseline cTnI was > or = 0.1 microg/L for 368, 395, and 418 patients with the Bayer Immuno 1(TM), ACS:180, and Dimension RxL assays, respectively. Correlation coefficients for the RxL with the ACS:180 and Bayer Immuno 1 results were 0.89 (P = 0.0001) and 0.87 (P = 0.0001), with a coefficient of 0.92 (P = 0.0001) for the ACS:180 and Bayer Immuno 1 assays. Patients with cTnI > or = 0.1 microg/L were at increased risk fo death or MI by 43 days (relative risk, 2.2-3.0; P <0.0006), regardless of the assay used. This prognostic capacity persisted among those with creatine kinase MB isoenzyme concentrations within the reference interval. Moreover, cTnI was the strongest multivariate predictor of death, MI, or urgent revascularization with adjusted odds ratios of 2.1-2.9 (P <0. 0006). CONCLUSION: This study demonstrates the prognostic efficacy of three independently developed cTnI assays at a threshold of 0.1 microg/L for the prediction of adverse clinical outcomes among patients with non-ST-elevation acute coronary syndromes.

Myoglobin, creatine-kinase-MB and cardiac troponin-I 60-minute ratios predict infarct-related artery patency after thrombolysis for acute myocardial infarction: results from the Thrombolysis in Myocardial Infarction study (TIMI) 10B.

OBJECTIVES: We examined the diagnostic performance of serum myoglobin, creatine-kinase-MB (CK-MB) and cardiac troponin-I (cTnI) for predicting the infarct-related artery (IRA) patency in patients receiving TNK-tissue plasminogen activator (TNK-tPA) therapy for acute myocardial infarction (AMI) in the Thrombolysis in Myocardial Infarction (TIMI) 10B trial. BACKGROUND: A reliable noninvasive serum marker of IRA patency is desired to permit early identification of patients with a patent IRA after thrombolysis. METHODS: We measured myoglobin, CK-MB and cTnI concentrations in sera obtained just before thrombolysis (T0) and 60 min later (T60) in 442 patients given TNK-tPA and who underwent coronary angiography at 60 min. RESULTS: Angiography at 60 min showed a patent IRA (TIMI flow grade 2, 3) in 344 and occluded IRA (TIMI flow grade 0, 1) in 98 patients. The median serum T60 concentration, the ratio of the T60 and T0 serum concentration (60-min ratio) and the slope of increase over 60 min for each serum marker were significantly higher in patients with patent arteries compared with patients with occluded arteries. The area under the receiver-operating characteristic (ROC) curve for diagnosis of occlusion was 0.71, 0.70 and 0.71 for the 60-min ratio of myoglobin, cTnI and CKMB, respectively. The 60-min ratios of > or =4.0 for myoglobin, > or =3.3 for CK-MB and > or =2.0 for cTnI yielded a probability of patency of 90%, 88% and 87%, respectively. CONCLUSIONS: The diagnostic performance of serum myoglobin, CK-MB and cardiac troponin-I (cTnI) 60-min ratios was similar. The probability of a patent IRA was very high (90%) in patients with 60-min myoglobin ratio > or =4.0, and early invasive interventions to establish IRA patency may not be necessary in this group. Serum marker determinations at baseline and 60-min after thrombolysis may permit rapid triage of patients receiving thrombolytic therapy by ruling out IRA occlusion.

Myoglobin, creatine kinase MB, and cardiac troponin-I to assess reperfusion after thrombolysis for acute myocardial infarction: results from TIMI 10A.

BACKGROUND: The availability of a reliable, noninvasive serum marker of reperfusion may permit early identification of patients with occlusion after thrombolysis who might benefit from further interventions. METHODS: We measured myoglobin, creatine kinase MB (CK-MB), and cardiac troponin-I (cTnI) concentrations in sera obtained just before thrombolysis (T0) and 60 minutes later (T60) in 30 patients given TNK-tPA for acute myocardial infarction as part of the Thrombolysis in Myocardial Infarction (TIMI) 10A trial. RESULTS: Angiography at T60 showed reperfusion (TIMI flow grade 2 to 3; n = 19) or occlusion (TIMI flow grade 0 to 1; n = 8). The median serum T60 concentration, the ratio of the T60 and T0 serum concentration, and the slope of increase over a 60-minute period for each serum marker were significantly higher in patients with patent arteries compared with patients with occluded arteries. The areas under the receiver operator characteristics curve for diagnosis of occlusion were 0.96, 0.91, and 0.87 for the T60 concentration of myoglobin, CK-MB and cTnI, respectively. Although the T60 levels of <469 ng/ml for myoglobin, <11.5 ng/ml for CK-MB, and < 1.1 ng/ml for cTnI identified all patients with occlusion, the specificity of myoglobin (94%) was higher than that of CK-MB (61%) and cTnI (67%). Similar results were obtained for the 60-minute ratios and 60-minute slopes for each marker, with indexes for myoglobin having the highest specificity. CONCLUSIONS: In this pilot study, noninvasive diagnosis of occlusion 60 minutes after thrombolysis was achieved with a high degree of sensitivity and specificity with the myoglobin, CK-MB, and cTnI concentrations measured at that time point. These preliminary findings may permit a new strategy for assessment of the success of reperfusion, with triage to rescue angioplasty for patients in whom the 60-minute cardiac marker values or indexes are consistent with occlusion of the infarct-related artery.

How fast is fast enough for clinical laboratory turnaround time? Measurement of the interval between result entry and inquiries for reports.

We measured the time interval from result entry by the clinical laboratory to inquiry for reports by clinicians as a proxy for the actual turnaround time required to meet current patient care needs and to determine whether different patterns of report inquiry occur among clinical departments. The study included 4,004 complete blood cell (CBC) count reports that were sought by the clinical services using the hospital information system. The median time to report inquiry was 90 minutes for routine inpatient tests, 35 minutes for stat inpatient tests, and 30 minutes for the stat outpatient CBC counts. Most reports (range, 86%-94%) from these three subgroups were requested within 4 hours from entry of the results in the hospital information system. Of the routine outpatient test reports, 14%, 23%, and 31% were requested within the first 2 hours, 4 hours, and 8 hours, respectively. Although the interdepartmental variations in the median time for report inquiry were statistically significant for routine inpatient tests, stat inpatient tests, and stat outpatient tests, inquiries for the preponderance of reports for all three groups were within the first 1.5 to 3 hours from entry of the results in the hospital information system. We conclude that the majority of CBC counts and other tests with effects on immediate patient care management must be performed very rapidly on site and cannot be moved off site without compromising current standards of medical practice.

Prediction of fetal lung maturity in infants of diabetic mothers using the FLM S/A and disaturated phosphatidylcholine tests.

The authors evaluated the performance of the amniotic fluid surfactant to albumin ratio (FLM S/A), and disaturated phosphatidylcholine (DSPC) tests in assessing fetal lung maturity in infants of mothers with insulin-dependent diabetes mellitus antedating pregnancy. The distribution of the study population (n = 180) by class of diabetes was class B (27%); class C (28%); class D (29%); class F, FR and T (8%); and class R patients (8%). The diagnosis of respiratory distress syndrome (RDS) was the standard for evaluating the performance of FLM S/A and DSPC. The mean estimated gestational age was 37.4 weeks. Three infants (1.7%) were diagnosed with RDS. All three were delivered before 36 weeks. FLM S/A at the cut-off for "maturity" of > or = 70 mg/g, had a sensitivity of 66.6%, specificity of 94.9%, positive predictive value (PPV) of 18.2%, and negative predictive value (NPV) of 99.4%. DSPC at the cut-off for "maturity" of 1,000 micrograms/dL, had identical sensitivity and NPV, but lower specificity (89.2%) and PPV (9.5%) than FLM S/A. Both tests mispredicted maturity in the same case of RDS. The false "mature" rate of FLM S/A was 0.6% (95% confidence interval 0.0%-3.2%). The FLM S/A result of > or = 70 mg/g, obtained at or near-term, is a reliable predictor of the absence of RDS in infants of mothers with diabetes mellitus antedating pregnancy.

Total serum calcium reference intervals in postmenopausal outpatients.

The distribution of values of serum calcium has been studied in the following four outpatient populations: premenopausal (n = 411) and postmenopausal women (n = 399), men less than 50 years old (n = 365) and men over 55 years old (n = 361). Their respective average total serum calcium values (mg/dl) were 9.42, 9.56, 9.53, and 9.45. The reference intervals derived for total serum calcium (mg/dl) were 8.4-10.3 (premenopausal women), 8.4-10.7 (postmenopausal women), 8.6-10.5 (men less than 50 years old), and 8.4-10.4 (men over 55 years old). Increased total serum calcium levels were observed in the postmenopausal women as compared with both premenopausal women (p < 0.001) and with men over 55 years old (p < 0.003). Eight percent of the values obtained in postmenopausal women were above the current reference interval, as compared to 1.7% in premenopausal women, and 3.3% in men over 55 years old. In conclusion, the age-related increase in total serum calcium in postmenopausal female outpatients warrants a higher upper limit of the reference interval for this subpopulation.

A predictive model for fetal lung maturity employing gestational age and test results.

Most laboratory tests for fetal lung maturity (FLM) are optimized to exclude false-negative predictions of absence of respiratory distress syndrome (RDS), with a reciprocal low predictive value for maturity. The authors employed FLM Surfactant/Albumin Ratio (FLM S/A) test results to construct a predictive model for FLM that included the obstetric estimates of gestational age. The charts of 388 newborns were abstracted and reviewed. The clinical outcome was the gold standard of the multivariate logistic analysis. Both the obstetric estimates of gestational age and the test result were significant predictors of the clinical outcome (P values of < .0002 and .001, respectively). The prediction rule for RDS as a function of both of these variables allows for adjustment of the test cutoffs, so that there is a consistent probability of RDS at the cutoff FLM S/A result for different gestational ages. Fetal lung maturity probability reporting may facilitate clinical decision-making.

The fiscal consequences of central vs distributed testing of glucose.

We have compared the operational, medical, and fiscal consequences of performing urgent glucose testing at the bedside vs in the central laboratory. The turnaround time (TAT) with bedside testing was only 1-2 min shorter than that from the central laboratory, to which specimens are sent by pneumatic tube and from which results are automatically broadcast by computer to the originating site. No significant adverse medical outcomes were associated with this difference in TAT. The cost of bedside testing is approximately twice that of central laboratory testing.

Quantification of medical and operational factors determining central versus satellite laboratory testing of blood gases.

Blood gas measurements performed at the central laboratory and at a satellite laboratory of Brigham and Women's Hospital were studied to determine the differences in quality, turnaround time (TAT), and cost. The quality in both laboratories, as determined by results on proficiency and quality control samples, satisfactorily met current standards for patient care. The central laboratory receives specimens for blood gas measurements through a pneumatic tube system and broadcasts results to computer terminals at the originating site, with a mean TAT of 6 minutes. The satellite laboratory, which is within the neonatal intensive care unit that it serves, has a mean TAT of 4.5 minutes. The difference is attributable to transit time in the pneumatic tube and accessioning time in the central laboratory. The total cost per reportable result was substantially higher for the satellite laboratory than for the central laboratory. The minor difference in TAT can be considered in a cost-benefit analysis that weighs medical utility criteria against cost.

Cost savings in a hospital clinical laboratory with a pay-for-performance incentive program for supervisors.

A pay-for-performance incentive program for clinical laboratory supervisors was developed and implemented at Brigham and Women's Hospital (Boston, Mass). It provides monetary rewards to personnel who directly produce cost savings in their area of responsibility. This reward system is new to the hospital laboratory but is commonly used in industry. Substantial true cost savings over and above previously established stringent budgets were achieved, 11% of which was returned to first-line supervisors in the form of a bonus. The program expanded the scope of professionalism for supervisors to include fiscal management.

Determination of ionized calcium in serum that has been exposed to air.

We examined changes in ionized calcium concentration in serum after its exposure to air. Samples with total protein concentrations ranging from 50 to 90 g/liter were equilibrated with CO2 in nitrogen (5/95, by vol) or CO2 alone, to produce pH values of 7.0 to 8.0. Ionized calcium was then measured with an Orion flow-through electrode system. Curves relating pH and ionized calcium concentration had statistically identical slopes regardless of protein concentration. A factor was derived, based on pH change, for correcting values for ionized calcium in serum exposed to air, and its validity was confirmed by comparing corrected values for samples allowed to stand at ambient temperature (23 degrees C) without anaerobic precautions with values initially obtained on anaerobic aliquots of the same samples.