Jay L. Bock

Evaluation of a New Rapid Quantitative Immunoassay for Serum Myoglobin Versus CK-MB for Ruling Out Acute Myocardial Infarction in the Emergency Department

STUDY OBJECTIVE To compare the predictive values of serum myoglobin and creatine kinase (CK)-MB for ruling out acute myocardial infarction in the emergency department. DESIGN Prospective, observational study. SETTING University teaching hospital. PARTICIPANTS One hundred eighty nine consecutive patients aged 30 years and older who presented within 12 hours from onset of chest discomfort, dyspnea, syncope, congestive heart failure, symptomatic dysrhythmia, pulmonary edema, or epigastric pain were entered into the study. Patients with trauma or renal failure were excluded. INTERVENTIONS Standardized history and physical examination and blood sampling for serum myoglobin (S-Mgb) and CK-MB were done at the time of presentation (T0) and 1 hour later (T1). RESULTS Using World Health Organization criteria, 22 acute myocardial infarction patients were identified. Mean time from symptom onset to presentation was 3.2 hours. S-Mgb was more sensitive than CK-MB at T0 and T1, 55% versus 23% (P < .05) and 73% versus 41% (P < .05), respectively. Respective specificities of S-Mgb versus CK-MB were 98% versus 99% (P = NS) at T0 and 97% versus 99% (P = NS) at T1. Negative predictive values of S-Mgb versus CK-MB were 94% versus 91% (P = NS) at T0 and 96% versus 93% (P = NS) at T1. The S-Mgb assay yielded quantitative results allowing the difference between the T0 and T1 values to be analyzed. A difference of 40 or more ng/mL between T0 and T1 was considered positive. When using a positive result in either the T0 or T1 value or a difference between the two values of 40 or more ng/mL, the sensitivity of S-Mgb was 91% (P < .05 versus CK-MB), the specificity was 96% (P = NS versus CK-MB), and the negative predictive value was 99% (95% confidence interval for S-Mgb, 97.0 to 100 versus CK-MB, 95% confidence interval, 88.9 to 96.6). CONCLUSION In the first hour of presentation to the ED, the rapid quantitative assay for S-Mgb was statistically more sensitive than CK-MB and had an excellent negative predictive value for ruling out acute myocardial infarction in patients with typical or atypical symptoms. Due to the relatively small sample size, we could not exclude the possibility that differences in specificity might become statistically significant (beta error) with a larger sample size of acute myocardial infarction patients.

Biomarkers of vitamin B-12 status in NHANES: a roundtable summary

A roundtable to discuss the measurement of vitamin B-12 (cobalamin) status biomarkers in NHANES took place in July 2010. NHANES stopped measuring vitamin B-12–related biomarkers after 2006. The roundtable reviewed 3 biomarkers of vitamin B-12 status used in past NHANES—serum vitamin B-12, methylmalonic acid (MMA), and total homocysteine (tHcy)—and discussed the potential utility of measuring holotranscobalamin (holoTC) for future NHANES. The roundtable focused on public health considerations and the quality of the measurement procedures and reference methods and materials that past NHANES used or that are available for future NHANES. Roundtable members supported reinstating vitamin B-12 status measures in NHANES. They noted evolving concerns and uncertainties regarding whether subclinical (mild, asymptomatic) vitamin B-12 deficiency is a public health concern. They identified the need for evidence from clinical trials to address causal relations between subclinical vitamin B-12 deficiency and adverse health outcomes as well as appropriate cutoffs for interpreting vitamin B-12–related biomarkers. They agreed that problems with sensitivity and specificity of individual biomarkers underscore the need for including at least one biomarker of circulating vitamin B-12 (serum vitamin B-12 or holoTC) and one functional biomarker (MMA or tHcy) in NHANES. The inclusion of both serum vitamin B-12 and plasma MMA, which have been associated with cognitive dysfunction and anemia in NHANES and in other population-based studies, was preferable to provide continuity with past NHANES. Reliable measurement procedures are available, and National Institute of Standards and Technology reference materials are available or in development for serum vitamin B-12 and MMA.

Biomarkers of folate status in NHANES: a roundtable summary

A roundtable to discuss the measurement of folate status biomarkers in NHANES took place in July 2010. NHANES has measured serum folate since 1974 and red blood cell (RBC) folate since 1978 with the use of several different measurement procedures. Data on serum 5-methyltetrahydrofolate (5MTHF) and folic acid (FA) concentrations in persons aged ≥60 y are available in NHANES 1999–2002. The roundtable reviewed data that showed that folate concentrations from the Bio-Rad Quantaphase II procedure (Bio-Rad Laboratories, Hercules, CA; used in NHANES 1991–1994 and NHANES 1999–2006) were, on average, 29% lower for serum and 45% lower for RBC than were those from the microbiological assay (MA), which was used in NHANES 2007–2010. Roundtable experts agreed that these differences required a data adjustment for time-trend analyses. The roundtable reviewed the possible use of an isotope-dilution liquid chromatography–tandem mass spectrometry (LC-MS/MS) measurement procedure for future NHANES and agreed that the close agreement between the MA and LC-MS/MS results for serum folate supported conversion to the LC-MS/MS procedure. However, for RBC folate, the MA gave 25% higher concentrations than did the LC-MS/MS procedure. The roundtable agreed that the use of the LC-MS/MS procedure to measure RBC folate is premature at this time. The roundtable reviewed the reference materials available or under development at the National Institute of Standards and Technology and recognized the challenges related to, and the scientific need for, these materials. They noted the need for a commutability study for the available reference materials for serum 5MTHF and FA.

Educating medical students in laboratory medicine: a proposed curriculum.

As the 100th anniversary of the Flexner report nears, medical student education is being reviewed at many levels. One area of concern, expressed in recent reports from some national health care organizations, is the adequacy of training in the discipline of laboratory medicine (also termed clinical pathology). The Academy of Clinical Laboratory Physicians and Scientists appointed an ad hoc committee to review this topic and to develop a suggested curriculum, which was subsequently forwarded to the entire membership for review. The proposed medical student laboratory medicine curriculum defines goals and objectives for training, provides guidelines for instructional methods, and gives examples of how outcomes can be assessed. This curriculum is presented as a potentially helpful outline for use by medical school faculty and curriculum committees.

Introduction of a Stat Laboratory Reduces Emergency Department Length of Stay

OBJECTIVES Emergency department (ED) length of stay (LOS) impacts patient satisfaction and overcrowding. Laboratory turnaround time (TAT) is a major determinant of ED LOS. The authors determined the impact of a Stat laboratory (Stat lab) on ED LOS. The authors hypothesized that a Stat lab would reduce ED LOS for admitted patients by 1 hour. METHODS This was a before-and-after study conducted at an academic suburban ED with 75,000 annual patient visits. All patients presenting to the ED during the months of August and October 2006 were considered. A Stat lab located within the central laboratory was introduced in September 2006 to reduce laboratory TAT. The test TATs and ED LOS before (August 2006) and after (October 2006) implementing the Stat lab for all ED patients were the data of interest. ED LOS before and after the Stat lab was introduced was compared with the Mann-Whitney U-test. A sample size of 5,000 patients in each group had 99% power to detect a 1-hour difference in ED LOS. RESULTS There were 5,631 ED visits before and 5,635 visits after implementing the Stat lab. Groups were similar in age (34 years vs. 36 years) and gender (51% males in both). The percentages of patients with laboratory tests before and after Stat lab implementation were 68.7 and 71.3%, respectively. Test TATs for admitted patients were significantly improved after the Stat lab introduction. Implementation of the Stat lab was associated with a significant reduction in the median ED LOS from 466 (interquartile range [IQR] = minutes before to 402 (IQR = 296-553) minutes after implementing the Stat lab. The effects of the Stat lab on ED LOS were less marked for discharged patients. CONCLUSIONS Introduction of a Stat lab dedicated to the ED within the central laboratory was associated with shorter laboratory TATs and shorter ED LOS for admitted patients, by approximately 1 hour.

Effects of commonly prescribed nonsteroidal anti-inflammatory drugs on thyroid hormone measurements

PURPOSE To assess the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on thyroid function tests. PATIENTS AND METHODS Eighty-nine patients receiving NSAIDs and 22 control subjects not taking NSAIDs were studied in a cross-sectional survey at Veterans Affairs and University hospitals. Measurements of serum thyroxine (T4), free T4 index, triiodothyronine (T3), and thyrotropin (thyroid-stimulating hormone [TSH]) were obtained for all subjects. RESULTS Serum T4 measurements were lowered only in salsalate-treated patients, while serum T3 was depressed in patients receiving salsalate, diclofenac sodium, and naproxen. Serum T4 and T3 were unchanged in patients treated with diflunisal, ibuprofen, indomethacin, piroxicam, or sulindac. Serum TSH was normal in all subjects. CONCLUSIONS Several NSAIDs can lower serum thyroid hormone concentrations, principally by interfering with the binding of T4 and T3 to serum carrier proteins; patients taking these drugs remain euthyroid. Awareness of these interactions may prevent unnecessary diagnostic or therapeutic interventions.

Comparison of Emergency Department Patient Classification by Point-of-Care and Central Laboratory Methods for Cardiac Troponin I

For patients admitted to the emergency department (ED) with suspected acute coronary syndrome, we compared results of a rapid, point-of-care whole blood assay for cardiac troponin I (Abbott i-STAT, Abbott Point-of-Care, East Windsor, NJ) (Tn-P) with an automated central laboratory plasma assay (Siemens TnI-Ultra, Siemens Medical Solutions Diagnostics, Tarrytown, NY) (Tn-U). Clinical data were obtained during a 6-month period during which ED patients were screened by Tn-P, with retesting of elevated results by Tn-U. Of 5,909 Tn-P results, 573 (9.7%) were elevated; these and a random selection of 137 negative specimens were retested by Tn-U. Of the specimens with elevated results, 4.5% retested negative by Tn-U, even though Tn-U typically gave about 50% higher results and had a lower manufacturer-specified 99th percentile cutoff. Of the negatives, 5.8% retested as elevated by Tn-U, but with levels no higher than 0.1 ng/mL (0.1 microg/L). Rapid whole blood testing for cardiac troponin I gave generally reliable patient classifications compared with plasma testing in the central laboratory, but besides missing small elevations, produced some apparent false-positives.

How Sensitive Is a Prostate-Specific Antigen Measurement?: How Sensitive Does It Need to Be?

Assays are now available that can measure very low concentrations of prostate-specific antigen (PSA), but their analytic performance and clinical utility are not well defined. This brief article highlights some of the clinical issues related to the limited prognostic significance of small changes in PSA concentrations in men with prostate cancer who have been treated with prostate ablation therapy. College of American Pathologists proficiency survey data are presented, illustrating the performance of commercial PSA assays with low PSA concentration survey samples tested between 1998 and 2002. The performance of the assays appears to be improving, but many of the currently used assays have intralaboratory coefficients of variation greater than 20% for PSA concentrations less than 0.4 ng/mL. Also, there are major differences in the level of PSA reported by various assays in these low concentration samples. These level differences (if they are also seen in clinical samples) may cause clinical problems when fixed serum PSA thresholds (eg, 0.2 ng/mL) are used to make clinical decisions related to prostate tumor recurrence.

Evaluation of CK-MB isoform analysis for early diagnosis of myocardial infarction.

Measurement of CK-MB and its isoforms by high-voltage electrophoresis has been proposed as a sensitive test for early detection of myocardial infarction (MI). We performed a prospective study of this test in 231 patients presenting to the Emergency Department with symptoms consistent with ischemic chest pain. Blood specimens were obtained at 0, 1, and 3 h following presentation, and plasma was immediately frozen and analyzed within 1 week by high-voltage electrophoresis for total CK-MB and isoforms. The test was considered positive whenever total CK-MB was elevated (>6 U/L) or the cardiac isoform MB2 was relatively increased (MB2 > 2 U/L and MB2/MB1 > 1.7). This test had a sensitivity of 68% overall and 55% for specimens collected within 3 h of symptom onset. It was positive within 3 h of presentation in 36/39 (92%) of patients with confirmed MI. Specificity was 92% overall and did not vary with time after symptoms. The CK-MB alone, at the cutoff of 6 U/L, had lower sensitivity overall (56%; p = 0.01) and within 3 h of onset (39%; p = 0.03), and higher specificity overall (98%; p < 0.001). Lowering the cutoff for CK-MB alone to match the sensitivity of the isoform test caused a greater loss of specificity. It is concluded that analysis of CK-MB by high-voltage electrophoresis is an effective method for rapid diagnosis of MI, with the isoform analysis enhancing early sensitivity.

25Mg NMR studies of magnesium binding to erythrocyte constituents

The binding of Mg2+ ion to ATP, ADP, AMP, 2,3-bisphosphyoglycerate (DPG), and hemoglobin has been studied by 25Mg NMR spectroscopy at 9.4 T. Addition of any of these ligands to a solution of 2 mM 25MgCl2 at pH 7.2 caused a progressive increase in linewidth, with no discernible chemical shift. ATP and ADP, which form tight 1:1 complexes with Mg2+, did not cause maximal broadening until present in several-fold excess, implying that bis(nucleotide) complexes also form. The studies showed progressively weaker Mg2+ binding to ATP, ADP, DPG, and AMP, consistent with published binding constants. Hemoglobin cause fairly little broadening, consistent with its known weak affinity for Mg2+. Competition studies determined ATP affinities for Ca2+ and H+ that were also in good agreement with published values. 25Mg NMR spectra of 2 mM bound 25Mg2+ were obtained with good signal to noise in less than 1 hr. The technique may now be a practical means for studying the binding of Mg2+ within erythrocytes and other cells.