Stacy E.F. Melanson

Multicenter analytical evaluation of a high-sensitivity troponin T assay.

BACKGROUND High-sensitivity cardiac troponin assays are being introduced clinically for earlier diagnosis of acute myocardial infarction (AMI). We evaluated the analytical performance of a high-sensitivity cardiac troponin T assay (hscTnT, Roche Diagnostics) in a multicenter, international trial. METHODS Three US and 5 European sites evaluated hscTnT on the Modular® Analytics E170, cobas® 6000, Elecsys 2010, and cobas® e 411. Precision, accuracy, reportable range, an inter-laboratory comparison trial, and the 99th percentile of a reference population were assessed. RESULTS Total imprecision (CVs) were 4.6-36.8% between 3.4 and 10.3 ng/L hscTnT. Assay linearity was up to 10,000 ng/L and the limit of blank and detection were 3 and 5 ng/L, respectively. The 99th percentile reference limit was 14.2 ng/L (n=533). No significant differences between specimen types, assay incubation time, or reagent lots existed. A substantial positive bias (76%) exists between the 4th generation and hscTnT assays at the low end of the measuring range (<50 ng/L). hscTnT serum pool concentrations were within 2SD limits of the mean of means in the comparison trial, indicating comparable results across multiple platforms and laboratories. CONCLUSION The Roche hscTnT assay conforms to guideline precision requirements and will likely identify additional patients with myocardial injury suspicious for AMI.

Measurement of Organochlorines in Commercial Over-the-Counter Fish Oil Preparations: Implications for Dietary and Therapeutic Recommendations for Omega-3 Fatty Acids and a Review of the Literature

CONTEXT The consumption of fish high in omega-3 fatty acids is advocated by the American Heart Association to decrease the risk of coronary artery disease. However, fish contain environmental toxins such as mercury, polychlorinated biphenyls, and organochlorine pesticides, which may negate the beneficial cardiovascular effects of fish meals. Toxin levels vary depending on both the fish source and the specific toxin, and neither farm-raised nor wild fish are toxin free. Fish oil supplements also prevent the progression of coronary artery disease and reduce cardiovascular mortality. However, only sparse data exist on the level of toxins in fish oil. In a previous study we showed that the amount of mercury in 5 over-the-counter brands of fish oil was negligible. OBJECTIVE To determine the concentrations of polychlorinated biphenyls and other organochlorines in 5 over-the-counter preparations of fish oil. DESIGN The contents of 5 commercial fish oil brands were sent for organochlorine analysis. RESULTS The levels of polychlorinated biphenyls and organochlorines were all below the detectable limit. CONCLUSIONS Fish oil supplements are more healthful than the consumption of fish high in organochlorines. Fish oils provide the benefits of omega-3 fatty acids without the risk of toxicity. In addition, fish oil supplements have been helpful in a variety of diseases, including bipolar disorder and depression.

Applying Lean/Toyota Production System Principles to Improve Phlebotomy Patient Satisfaction and Workflow

Our goals were to improve the overall patient experience and optimize the blood collection process in outpatient phlebotomy using Lean principles. Elimination of non-value-added steps and modifications to operational processes resulted in increased capacity to handle workload during peak times without adding staff. The result was a reduction of average patient wait time from 21 to 5 minutes, with the goal of drawing blood samples within 10 minutes of arrival at the phlebotomy station met for 90% of patients. In addition, patient satisfaction increased noticeably as assessed by a 5-question survey. The results have been sustained for 10 months with staff continuing to make process improvements.

Cardiac troponin assays: a view from the clinical chemistry laboratory.

Many clinical chemistry laboratories perform troponin testing to aid in the diagnosis of acute coronary syndrome (ACS). Laboratories must interact with clinicians to establish diagnostic cut points, achieve acceptable assay performance, and troubleshoot questionable findings. Here we present 3 hypothetical scenarios related to troponin testing in the clinical chemistry laboratory. Case Presentation 1: J.P. is an obese 55-year-old male with a history of gastroesophageal reflux disease who presents to the emergency department with substernal chest pain that he attributes to a “large meal.” J.P. is pale and diaphoretic. An ECG shows tachycardia with normal sinus rhythm. J.P.’s troponin levels (decision limit >0.04 μg/L) at presentation and at 6 and 12 hours after presentation are 0.09, 4.41, and 19.62 μg/L, respectively. Cardiac troponin (cTn) has established itself firmly as the “gold standard” in the diagnosis of ACS. cTn should be measured in all patients presenting with symptoms suggestive of ACS, in conjunction with physical examination and ECG.1 Because of the specificity of cTn for myocardial damage, a single cTn above the decision limit, along with clinical evidence, is indicative of myocardial injury. However, serial testing can be useful, depending on clinical presentation and onset of symptoms. cTn is a protein complex, located along the thin filaments of myofibrils, that regulates the contraction of cardiac muscle. It is composed of 3 distinct gene products. cTnC binds calcium, cTnT attaches to tropomyosin on thin filaments, and cTnI inhibits actomyosin ATPase. Expression of each subunit is cardiac restricted. The cardiac isoforms of cTnI and cTnT have additional unique N-terminal amino acid sequences, which allows for specific antibody and assay development and detection of each component in the bloodstream. The diagnostic utilities of cTnI and cTnT are comparable. Most cTn assays are sandwich immunoassays that use either monoclonal or polyclonal antibodies. It is essential …

Selecting automation for the clinical chemistry laboratory.

CONTEXT Laboratory automation proposes to improve the quality and efficiency of laboratory operations, and may provide a solution to the quality demands and staff shortages faced by todays clinical laboratories. Several vendors offer automation systems in the United States, with both subtle and obvious differences. Arriving at a decision to automate, and the ensuing evaluation of available products, can be time-consuming and challenging. Although considerable discussion concerning the decision to automate has been published, relatively little attention has been paid to the process of evaluating and selecting automation systems. OBJECTIVE To outline a process for evaluating and selecting automation systems as a reference for laboratories contemplating laboratory automation. DESIGN Our Clinical Chemistry Laboratory staff recently evaluated all major laboratory automation systems in the United States, with their respective chemistry and immunochemistry analyzers. Our experience is described and organized according to the selection process, the important considerations in clinical chemistry automation, decisions and implementation, and we give conclusions pertaining to this experience. RESULTS Including the formation of a committee, workflow analysis, submitting a request for proposal, site visits, and making a final decision, the process of selecting chemistry automation took approximately 14 months. We outline important considerations in automation design, preanalytical processing, analyzer selection, postanalytical storage, and data management. CONCLUSIONS Selecting clinical chemistry laboratory automation is a complex, time-consuming process. Laboratories considering laboratory automation may benefit from the concise overview and narrative and tabular suggestions provided.

Implementation of a highly sensitive cardiac troponin I assay : Test volumes, positivity rates and interpretation of results

BACKGROUND While more sensitive cardiac troponin (cTn) assays may overcome current limitations in diagnosing acute coronary syndrome (ACS), clinicians and laboratorians are concerned about the clinical impact of higher rates of cTn positivity. METHODS We collected statistics on test volume and positivity rates before and after the implementation of a more sensitive assay. We divided patients into 6 groups based on their cardiac troponin I (cTnI) results and utilized additional laboratory test results to determine the impact of the new assay. In addition, we assessed the clinical significance of low-positive cTnI results (0.05-0.10 microg/l). RESULTS Lowering the diagnostic cutoff from 0.10 to 0.04 microg/l increased the number of positive test results by 44.2% hospital-wide and 114.4% in the emergency department without significantly changing test volume. In some patients, low-positive results were part of the typical rise and fall of cTnI consistent with myocardial damage. Diagnosis was more challenging in patients with consistently low-positive results. Patients in this group were significantly more likely to have impaired renal function than those with cTnI elevations >0.10 microg/l. CONCLUSIONS More sensitive cTn assays will increase the number of positive results and allow for earlier detection of cardiac injury while also detecting non-ACS related pathologies.

Elevation of Myeloperoxidase in Conjunction With Cardiac-Specific Markers After Marathon Running

Cardiac-related death has been reported following strenuous exercise, and biochemical markers predicting adverse outcomes would be useful. Despite the fact the myeloperoxidase (MPO) release may precede myocardial injury and identify at-risk patients earlier than traditional markers, information on the effects of marathon running on MPO levels is lacking. We measured MPO in conjunction with the creatine kinase MB fraction (CK-MB), myoglobin, troponin T (TnT), and N-terminal B-type natriuretic peptide (NT-proBNP) in 24 athletes before and after a marathon race. Of the 24 athletes, 22 (92%) had an increased MPO level, and the mean MPO level increased from 281.44 pmol/L to 785.21 pmol/L (P < .0001). Results for 14 (58%) of the athletes reached or exceeded the manufacturers recommended clinical threshold. The increases in CK-MB, myoglobin, TnT, and NT-proBNP also reached statistical significance. Although the elevation in MPO most likely represents a systemic inflammatory response, the concurrent elevations in TnT and NT-proBNP suggest that myocardial injury cannot be excluded.

The Utility of Immunoassays for Urine Drug Testing

Substance abuse is a significant problem in the United States, with cocaine, marijuana, alcohol and heroin as the most commonly abused drugs. This article focuses on urine drug testing to evaluate potential drug abuse or overdose in the emergent care setting using qualitative immunoassays. Discussion is included regarding the principles of how to validate qualitative immunoassays; how to decide on appropriate specimen type, test menu and cutoff; the limitations of immunoassays; how to communicate test results to clinicians; and use of urine drug testing at point of care.

Utilization of Arterial Blood Gas Measurements in a Large Tertiary Care Hospital

We describe the patterns of utilization of arterial blood gas (ABG) tests in a large tertiary care hospital. To our knowledge, no hospital-wide analysis of ABG test utilization has been published. We analyzed 491 ABG tests performed during 24 two-hour intervals, representative of different staff shifts throughout the 7-day week. The clinician ordering each ABG test was asked to fill out a utilization survey. The most common reasons for requesting an ABG test were changes in ventilator settings (27.6%), respiratory events (26.4%), and routine (25.7%). Of the results, approximately 79% were expected, and a change in patient management (eg, a change in ventilator settings) occurred in 42% of cases. Many ABG tests were ordered as part of a clinical routine or to monitor parameters that can be assessed clinically or through less invasive testing. Implementation of practice guidelines may prove useful in controlling test utilization and in decreasing costs.

Optimizing Urine Drug Testing for Monitoring Medication Compliance in Pain Management

BACKGROUND It can be challenging to successfully monitor medication compliance in pain management. Clinicians and laboratorians need to collaborate to optimize patient care and maximize operational efficiency. The test menu, assay cutoffs, and testing algorithms utilized in the urine drug testing panels should be periodically reviewed and tailored to the patient population to effectively assess compliance and avoid unnecessary testing and cost to the patient. OBJECTIVE Pain management and pathology collaborated on an important quality improvement initiative to optimize urine drug testing for monitoring medication compliance in pain management. METHODS We retrospectively reviewed 18 months of data from our pain management center. We gathered data on test volumes, positivity rates, and the frequency of false positive results. We also reviewed the clinical utility of our testing algorithms, assay cutoffs, and adulterant panel. In addition, the cost of each component was calculated. RESULTS The positivity rate for ethanol and 3,4-methylenedioxymethamphetamine were <1% so we eliminated this testing from our panel. We also lowered the screening cutoff for cocaine to meet the clinical needs of the pain management center. In addition, we changed our testing algorithm for 6-acetylmorphine, benzodiazepines, and methadone. For example, due the high rate of false negative results using our immunoassay-based benzodiazepine screen, we removed the screening portion of the algorithm and now perform benzodiazepine confirmation up front in all specimens by liquid chromatography-tandem mass spectrometry. CONCLUSION Conducting an interdisciplinary quality improvement project allowed us to optimize our testing panel for monitoring medication compliance in pain management and reduce cost.