Method Verification Shows a Negative Bias between 2 Procalcitonin Methods at Medical Decision Concentrations.

BACKGROUND: Procalcitonin (PCT) concentration increases as a result of systemic inflammation owing to bacterial infection. Many PCT algorithms and medical decision concentrations (MDCs) have been clinically validated using the B·R·A·H·M·S PCT™ sensitive Kryptor™ assay. Alternative PCT assays have recently been approved by the Food and Drug Administration for clinical use in the US and require method verification before clinical implementation. METHODS: Precision, sensitivity, linearity, reportable range, and reference intervals were verified for the Architect B·R·A·H·M·S PCT assay. Accuracy of the Architect B·R·A·H·M·S PCT assay was evaluated by comparison with the B·R·A·H·M·S PCT sensitive Kryptor assay. RESULTS: The Architect B·R·A·H·M·S PCT assay was found to be precise (CV, ≤4.6%), sensitive (limit of blank, 0.001 ng/mL; limit of quantitation, ≤0.01 ng/mL), and linear according to the manufacturer's claims. The analytical measurement range (0.20-100.00 ng/mL) and the reference interval (≤0.07 ng/mL) were also verified. Patient result comparisons indicated high agreement at 0.10 ng/mL and 0.25 ng/mL and reduced positive agreement at 0.50 ng/mL and 2.00 ng/mL MDCs owing to negative bias compared with the B·R·A·H·M·S PCT sensitive Kryptor assay. CONCLUSIONS: The Architect B·R·A·H·M·S PCT assay meets most performance specifications claimed by the manufacturer; however, negative bias at 0.50 ng/mL and 2.00 ng/mL PCT concentrations is evident.

Peritoneal and Pleural Fluid Chemistry Measurements Performed on Three Chemistry Platforms.

BACKGROUND: Chemistry testing is requested for body fluid (BF) specimens despite the lack of assays approved by the US Food and Drug Administration (FDA). The criteria for categorizing fluids as transudate or exudate are not validated across analyzers. OBJECTIVE: To compare BF chemical analysis and classification by different analyzers. METHODS: We analyzed 10 pleural and 18 peritoneal fluids with corresponding plasma specimens using the Vitros 5,1 FS; Abbott ARCHITECT ci8200; and Roche Modular P platforms. Total protein (TP) and lactate dehydrogenase (LDH) were measured for pleural fluids. Light's criteria were applied. Albumin was measured for peritoneal specimens, and the plasma-ascites-albumin gradient was calculated. RESULTS: TP results showed agreement. The Vitros LDH assay produced higher fluid:plasma ratios. Classification by Light's criteria resulted in 1 discrepancy (ARCHITECT). Albumin results showed agreement. There were 2 discrepant gradient interpretations (Vitros). CONCLUSIONS: These data suggest that analyses of pleural and peritoneal fluids using these platforms are diagnostically interchangeable.

A Reflex Protocol for Creatinine Testing Reduces Costs and Maintains Patient Safety.

BACKGROUND: The Jaffe and enzymatic methods are the 2 most common methods for creatinine measurement. The Jaffe method is less expensive but subject to interferences. Some laboratory scientists have called for the Jaffe method to be retired. OBJECTIVE: To determine the most cost-effective and safe protocol for creatinine measurement. METHOD: We performed a retrospective database review of all outpatient creatinine measurements for 1 year, testing the risk-based reflex testing protocol we had implemented for creatinine measurement. Samples were first measured using the Jaffe method and were reflexed to the enzymatic method if the estimated glomerular filtration rate (eGFR) was between 55 and 65 mL per min per 1.73 m2. RESULTS: There were 104,530 creatinine measurements, of which 11,420 (10.9%) were reflexed to the enzymatic method. The Jaffe method had a positive bias of 0.08 mg per dL (-6.14 mL/min/1.73 m2 eGFR). A total of 3.4% of the paired reflexed specimens were discordant. Also, 133 (1.2%) of the Jaffe results were classified as false negatives and 3411 (29.9%) were classified as false positives. None of the false-negative results and 5 of the false-positive results were considered clinically significant. Using the reflex protocol saved approximately $40,000 per year. CONCLUSIONS: The reflex protocol for creatinine measurement can reduce costs with acceptable risk.

Appropriateness of Plasma Transfusion: A College of American Pathologists Q-Probes Study of Guidelines, Waste, and Serious Adverse Events.

CONTEXT: - Plasma transfusion guidelines support patient care and safety, management of product wastage, and compliance; yet, there is little information across multiple institutions about use of and adherence to plasma transfusion guidelines. OBJECTIVE: - To survey multiple institutions regarding their plasma transfusion guidelines and compliance, plasma wastage rates, and incidence of transfusion reactions associated with plasma transfusion. DESIGN: - The College of American Pathologists Q-Probes model was used to collect data from 89 participating institutions. Each site was asked to provide data relevant to its most recent 40 adult patient plasma transfusion episodes, and complete a questionnaire regarding plasma transfusion guidelines, utilization and wastage of plasma, and transfusion reactions related to plasma transfusion. RESULTS: - The participating institutions reported a total of 3383 evaluable plasma transfusion episodes with transfusion of 9060 units of plasma. Compliance with institution-specific guidelines was seen in 3018 events (89%). Pretransfusion and posttransfusion coagulation testing was done in 3281 (97%) and 3043 (90%) of these episodes, respectively. Inappropriate criteria were noted for more than 100 transfusion episodes. Thirty-two plasma transfusion episodes (1%) were associated with a transfusion reaction. Serious and fatal reactions were reported. Median plasma wastage rate for the year preceding the study was 4.5%. CONCLUSIONS: - Most participating institutions are compliant with plasma transfusion guidelines based on published references, supported by appropriate testing. With transfusions for indications that lack evidence of efficacy and incidence of transfusion reactions, there is an ongoing role for transfusion service leaders to continue to update and monitor plasma transfusion practices.

Process Optimization to Improve Immunosuppressant Drug Testing Turnaround Time.

OBJECTIVES: Timely reporting of immunosuppressant (ISP) drug level results is needed for transplant patient management. This study characterized the local ISP testing process, identified bottlenecks and implemented process improvements to meet turnaround time requirements. METHODS: Laboratory information time stamps, direct observation and discussion with staff were used to construct a value stream map of the ISP testing process to identify process bottlenecks. Improvements were implemented to attain the required turnaround time. RESULTS: Baseline performance of the existing ISP process (seven weeks, n = 272 samples) indicated that only 28% of samples were reported by 2:00 pm Major bottlenecks were identified to be the analytical run schedule, instrument delays, difficulty identifying ISP samples at intake, and difficulty collecting specimens. Process changes resulted in a median of 76% samples reported by 2:00 pm CONCLUSIONS: : Adjusting ISP collection and analysis processes improved the laboratory's ability to meet physician requested result reporting time of 2:00 pm.

A Risk Assessment of the Jaffe vs Enzymatic Method for Creatinine Measurement in an Outpatient Population.

BACKGROUND: The Jaffe and enzymatic methods are the two most common methods for measuring serum creatinine. The Jaffe method is less expensive than the enzymatic method but is also more susceptible to interferences. Interferences can lead to misdiagnosis but interferences may vary by patient population. The overall risk associated with the Jaffe method depends on the probability of misclassification and the consequences of misclassification. This study assessed the risk associated with the Jaffe method in an outpatient population. We analyzed the discordance rate in the estimated glomerular filtration rate based on serum creatinine measurements obtained by the Jaffe and enzymatic method. METHODS: Method comparison and risk analysis. Five hundred twenty-nine eGFRs obtained by the Jaffe and enzymatic method were compared at four clinical decision limits. We determined the probability of discordance and the consequence of misclassification at each decision limit to evaluate the overall risk. RESULTS: We obtained 529 paired observations. Of these, 29 (5.5%) were discordant with respect to one of the decision limits (i.e. 15, 30, 45 or 60 ml/min/1.73m2). The magnitude of the differences (Jaffe result minus enzymatic result) were significant relative to analytical variation in 21 of the 29 (72%) of the discordant results. The magnitude of the differences were not significant relative to biological variation. The risk associated with misclassification was greatest at the 60 ml/min/1.73m2 decision limit because the probability of misclassification and the potential for adverse outcomes were greatest at that decision limit. CONCLUSION: The Jaffe method is subject to bias due to interfering substances (loss of analytical specificity). The risk of misclassification is greatest at the 60 ml/min/1.73m2 decision limit; however, the risk of misclassification due to bias is much less than the risk of misclassification due to biological variation. The Jaffe method may pose low risk in selected populations if eGFR results near the 60 ml/min/1.73m2 decision limit are interpreted with caution.

Practices for Identifying and Rejecting Hemolyzed Specimens Are Highly Variable in Clinical Laboratories.

CONTEXT: Hemolysis is an important clinical laboratory quality attribute that influences result reliability. OBJECTIVE: To determine hemolysis identification and rejection practices occurring in clinical laboratories. DESIGN: We used the College of American Pathologists Survey program to distribute a Q-Probes-type questionnaire about hemolysis practices to Chemistry Survey participants. RESULTS: Of 3495 participants sent the questionnaire, 846 (24%) responded. In 71% of 772 laboratories, the hemolysis rate was less than 3.0%, whereas in 5%, it was 6.0% or greater. A visual scale, an instrument scale, and combination of visual and instrument scales were used to identify hemolysis in 48%, 11%, and 41% of laboratories, respectively. A picture of the hemolysis level was used as an aid to technologists' visual interpretation of hemolysis levels in 40% of laboratories. In 7.0% of laboratories, all hemolyzed specimens were rejected; in 4% of laboratories, no hemolyzed specimens were rejected; and in 88% of laboratories, some specimens were rejected depending on hemolysis levels. Participants used 69 different terms to describe hemolysis scales, with 21 terms used in more than 10 laboratories. Slight and moderate were the terms used most commonly. Of 16 different cutoffs used to reject hemolyzed specimens, moderate was the most common, occurring in 30% of laboratories. For whole blood electrolyte measurements performed in 86 laboratories, 57% did not evaluate the presence of hemolysis, but for those that did, the most common practice in 21 laboratories (24%) was centrifuging and visually determining the presence of hemolysis in all specimens. CONCLUSIONS: Hemolysis practices vary widely. Standard assessment and consistent reporting are the first steps in reducing interlaboratory variability among results.

Clinical Laboratory Quality Practices When Hemolysis Occurs.

CONTEXT: Hemolyzed specimens delay clinical laboratory results, proliferate unnecessary testing, complicate physician decisions, injure patients indirectly, and increase health care costs. OBJECTIVE: To determine quality improvement practices when hemolysis occurs. DESIGN: We used the College of American Pathologists (CAP) Survey Program to distribute a Q-Probes-type questionnaire about hemolysis practices to CAP Chemistry Survey participants. RESULTS: Of 3495 participants sent the questionnaire, 846 (24%) responded. Although 85%, 69%, and 55% of participants had written hemolysis policies for potassium, lactate dehydrogenase, and glucose, respectively, only a few (46%, 40%, and 40%) had standardized hemolysis reports between their primary and secondary chemistry analyzers for these 3 analytes. Most participants (70%) had not attempted to validate the manufacturers' hemolysis data for these 3 analytes; however, essentially all who tried, succeeded. Forty-nine percent of participants had taken corrective action to reduce hemolysis during the past year and used, on average, 2.4 different actions, with collection and distribution of hemolysis data to administrative leadership (57%), troubleshooting outliers (55%), retraining phlebotomist (53%), and establishment of quality improvement teams among the laboratory and at problem locations (37%) being the most common actions. When asked to assess their progress in reducing hemolysis, 70% noted slow to no progress, and 2% gave up on improvement. Upon measuring potassium, lactate dehydrogenase, and glucose, approximately 60% of participants used the same specimen flag for hemolysis as for lipemia and icterus. CONCLUSIONS: Hemolysis decreases the quality and increases the cost of health care. Practices for measuring, reporting, and decreasing hemolysis rates need improvement.

Red blood cell transfusion practices: a College of American Pathologists Q-Probes study of compliance with audit criteria in 128 hospitals.

CONTEXT: Most information on compliance with audit criteria for red blood cell (RBC) transfusions comes from single institutions; few studies have compared practices among many hospitals. OBJECTIVE: To survey a cross-section of hospitals in 2008 for criteria and compliance with RBC transfusion guidelines, using the College of American Pathologists Q-Probes format. DESIGN: One hundred twenty-eight hospitals, representing about 4.5% (724,332 of 16,212,000) of all annual RBC usage in the United States, provided information on their RBC audit practices and their recent rates of compliance. They also each examined 50 RBC transfusion episodes for compliance with their guidelines. RESULTS: The participants' median, pretransfusion hemoglobin thresholds for audit review were 8.0 to 8.9 g/dL for most clinical settings and 9.0 to 9.9 g/dL for patients with underlying cardiopulmonary disease. For the transfusion episodes examined, 60% (2063 of 6518) were for a single unit. The median of the institutional averages for pretransfusion hemoglobin was 8.1 g/dL, and the median rate of compliance was 69% (range, 0%-100%). Involvement by a pathologist or transfusion medicine expert in the audit system was associated with more-strict audit criteria and better compliance. CONCLUSIONS: Median hemoglobin thresholds for RBC transfusion audits were somewhat higher than currently evolving recommendations, but opportunities for improvement were provided by expert involvement and by the growing frequency of 1-unit transfusions.

A mathematical procedure to estimate the impact of a change in method on discordance or misclassification at a decision limit in laboratory method comparison studies.

BACKGROUND: Laboratories often adopt new methods. It would be useful to have a statistical procedure to estimate the incremental impact of a change in assay. METHODS: Mathematical modeling, statistical analysis, and case example. RESULTS: We derived equations to estimate the proportion of discordant results that can be attributed to the new laboratory method. The calculations were demonstrated by comparing eGFR values based on creatinine values determined using the enzymatic method (existing method) and Jaffe method (new method). The discordance rate at the 60 ml/min eGFR decision limit was 3.15%. In this example, we estimated that 60% of the discordant results could be attributed to the Jaffe method. CONCLUSION: The sources of discordance in a laboratory method comparison study can be divided into three categories: The baseline discordance due to imprecision in the established method, the incremental discordance due to imprecision in the new method, and lack of analytical specificity. Discordance due to imprecision can be attributed to each individual method. Discordance due to bias can be attributed to individual methods if information is available to estimate the rate of biased observations in either method. Such information can be used to estimate the incremental cost effectiveness associated with the adoption of a new method.

Clinical consequences of specimen rejection: a College of American Pathologists Q-Probes analysis of 78 clinical laboratories.

CONTEXT: Clinical laboratory specimens may be rejected as unsuitable for analysis for a variety of reasons and specimen rejection may have significant clinical consequences. OBJECTIVE: To quantify the clinical consequences of specimen rejection and determine the impact of laboratories' policies and practices on these consequences. DESIGN: Participants prospectively reviewed consecutive blood and urine specimens submitted to the chemistry and/or hematology laboratories to identify rejected specimens. For each rejected specimen, the patient's age, specimen type, testing priority, rejection reason, time from specimen receipt to receipt of recollected/relabeled specimen, recollection method, and test result time were recorded. Specimen/test abandonment was determined by failure to recollect or relabel a rejected specimen. Each laboratory's policy regarding relabeling of incorrectly labeled specimens was recorded, along with how many relabeled specimens were subsequently discovered to be mislabeled. RESULTS: Specimen rejection led to a (1) high rate of specimen recollection, (2) delay in result availability (median of 65 minutes), and (3) high rate of specimen/test abandonment. Longer test result delay was associated with higher hospital bed size; and higher test abandonment rate, with failure of the laboratory to request specimen recollection. Relabeling of incorrectly labeled specimens was found to be of little benefit and was associated with a substantial percentage of subsequently mislabeled specimens. CONCLUSION: Specimen rejection has significant clinical consequences, including patient discomfort, significant delay in result availability, and high rate of specimen/test abandonment. Allowing routine relabeling of incorrectly labeled specimens is a dangerous practice, with little measureable benefit and with an increased risk to patient safety.

Utility of repeat testing of critical values: a Q-probes analysis of 86 clinical laboratories.

CONTEXT: A common laboratory practice is to repeat critical values before reporting the test results to the clinical care provider. This may be an unnecessary step that delays the reporting of critical test results without adding value to the accuracy of the test result. OBJECTIVES: To determine the proportions of repeated chemistry and hematology critical values that differ significantly from the original value as defined by the participating laboratory, to determine the threshold differences defined by the laboratory as clinically significant, and to determine the additional time required to analyze the repeat test. DESIGN: Participants prospectively reviewed critical test results for 4 laboratory tests: glucose, potassium, white blood cell count, and platelet count. Participants reported the following information: initial and repeated test result; time initial and repeat results were first known to laboratory staff; critical result notification time; if the repeat result was still a critical result; if the repeat result was significantly different from the initial result, as judged by the laboratory professional or policy; significant difference threshold, as defined by the laboratory; the make and model of the instrument used for primary and repeat testing. RESULTS: Routine, repeat analysis of critical values is a common practice. Most laboratories did not formally define a significant difference between repeat results. Repeated results were rarely considered significantly different. Median repeated times were at least 17 to 21 minutes for 10% of laboratories. Twenty percent of laboratories reported at least 1 incident in the last calendar year of delayed result reporting that clinicians indicated had adversely affected patient care. CONCLUSION: Routine repeat analysis of automated chemistry and hematology critical values is unlikely to be clinically useful and may adversely affect patient care.

Utilization of stat test priority in the clinical laboratory: a College of American Pathologists q-probes study of 52 institutions.

CONTEXT: Utilization of stat testing priority is a balance between safe, efficient patient management and resource expenditure. OBJECTIVE: To determine the rate of stat testing, compare rates among institutions, and determine the distribution of turnaround time expectations for different turnaround time priorities. DESIGN: During a 7-day period, participants prospectively determined the total number of chemistry, hematology, and coagulation billable tests from inpatients and emergency department patients. Among these, the total numbers of billable tests performed stat were identified. Laboratories also reported the levels of test priority they offered and turnaround expectations for each level of test priority. RESULTS: Fifty institutions submitted data for the study, with 2 additional participants submitting partial results. Participants identified 639 589 chemistry, hematology, and coagulation billable tests, with 229 896 (35.9%) performed stat. The stat rate varied from 21.3% at the 10th percentile to 55.4% at the 90th percentile, with a median of 37.0% of participants' tests performed stat. Laboratories include a mean of 206 tests in chemistry, hematology, and coagulation test menus, with 67% of these tests offered stat. The fraction of the test menu offered stat varied from 29.0% at the 10th percentile to 97.8% at the 90th percentile, with a median of 73.3% of tests on the menu offered stat. The most common number of testing priorities offered by participating laboratories was 3 (44.2%). CONCLUSIONS: Among the 52 participating laboratories, the median stat testing rate was 37.0% and a median 73.3% of the test menu was offered stat.

Method comparison of the Ortho Vitros Fusion 5,1 chemistry analyzer and the Roche COBAS Integra 400 for urine drug screen testing in the emergency department.

Exposure to drugs and toxins is a major cause for the rising number of emergency department visits each year. Immunoassays are commonly used in the emergency department to provide rapid turnaround time for acute care. The purpose of this study was to compare two automated immunoassay chemistry analyzers to determine which platform produced the fewest number of false positive/negative results. Residual patient urine samples were were collected for each of the following drugs/drug classes: cocaine (n = 40), opiates (n = 45), and amphetamines (n = 54) and confirmed either positive or negative by mass spectrometry. Split sample analyses of these specimens were performed on both the Roche COBAS INTEGRA 400 plus and Ortho Vitros 5,1 FS instruments. The results from the two chemistry analyzers were compared to confirmed results. Both immunoassays were prone to false positive results for cocaine and false negative results for opiates and amphetamines. The Vitros Fusion analyzer generated fewer false positive and false negative results for opiate and amphetamine testing than the Roche Integra, but the platforms performed comparably for cocaine.

Should the qualitative serum pregnancy test be considered obsolete?

Qualitative and quantitative serum human chorionic gonadotropin (hCG) tests are used to diagnose pregnancy. We assessed physicians' perceptions and compared turnaround times (TATs) and performance characteristics of both tests. We surveyed 1,058 physicians about their perceptions of hCG tests. Seven months of TAT data were analyzed. hCG was measured in all qualitative samples. Pregnancy status was determined by chart review. Of the physicians surveyed, 183 responded. Forty-nine percent preferred qualitative over quantitative serum tests for determining pregnancy status. Physicians were willing to wait 45 minutes for results from either test. Qualitative tests are performed faster than quantitative tests, but TATs were not significantly different when sample transport time was considered. The negative predictive value of both tests was 99.9%. Qualitative serum hCG testing could be replaced by quantitative hCG tests, but there is no clear advantage to doing so.

Managing transfusion service quality.

CONTEXT: Providing blood products for transfusions is a complex process subject to errors both within and outside the transfusion service. Transfusion-related errors can have grave consequences for the patient undergoing transfusion. As with many processes performed within health care systems, there is an expectation of error-free practice. Although this is an unobtainable goal, a focused quality-management plan, employing a medical event reporting system in a just working environment, can effect measurable system-quality improvement. OBJECTIVE: To illustrate the intrinsic value of quality-improvement activities through discussion of examples of quality misadventures from our transfusion service during the past 20 years. DATA SOURCES: Examples of quality-improvement activities were extracted from our quality-system archives. The published literature on transfusion quality was reviewed. CONCLUSIONS: Active reporting, structured investigation, and systematic resolution of transfusion-related errors are effective methods for improving and maintaining transfusion quality.

Evaluation of the integrated E-Z split key(®) cup II for rapid detection of twelve drug classes in urine.

The availability of point-of-care (POC) medical devices for drug testing has surged. Reduction in turnaround time, and hence, rapid results are attractive, particularly to acute care facilities, rehabilitation facilities and specialized clinics such as pain management clinics. Here we describe our validation results for the Integrated E-Z Split Key Cup II, a low-cost, rapid urine test that utilizes competitive immunoassay technology to detect 12 drugs or drug classes of commonly abused drugs. Positivity is based on the absence of a colored band at a labeled portion of the detection strip; a negative result produces a distinct, colored band. Using reagent-grade standards, the apparent cut-off for each of the drugs was challenged. The stability of the results was monitored over time. Five urine samples known to be negative for all drug categories and 24 patient samples confirmed positive for a total of 95 drugs and/or drug metabolites claimed to be detected by the device were tested. Adulterants and potential cross-reacting compounds were also evaluated. One false-positive result for benzodizepines was observed. One false-negative result for barbiturates was observed, but was resolved. Overall, the cups demonstrated excellent sensitivity, specificity, and diagnostic efficiency for all drugs represented.

Blood bank safety practices: mislabeled samples and wrong blood in tube--a Q-Probes analysis of 122 clinical laboratories.

CONTEXT: Although a rare occurrence, ABO incompatible transfusions can cause patient morbidity and mortality. Up to 20% of all mistransfusions are traced to patient misidentification and/or sample mislabeling errors that occur before a sample arrives in the laboratory. Laboratories play a significant role in preventing mistransfusion by identifying wrong blood in tube and rejecting mislabeled samples. OBJECTIVES: To determine the rates of mislabeled samples and wrong blood in tube for samples submitted for ABO typing and to survey patient identification and sample labeling practices and sample acceptance policies for ABO typing samples across a variety of US institutions. DESIGN: One hundred twenty-two institutions prospectively reviewed inpatient and outpatient samples submitted for ABO typing for 30 days. Labeling error rates were calculated for each participant and tested for associations with institutional demographic and practice variable information. Wrong-blood-in-tube rates were calculated for the 30-day period and for a retrospective 12-month period. A concurrent survey collected institution-specific sample labeling requirements and institutional policies regarding the fate of mislabeled samples. RESULTS: For all institutions combined, the aggregate mislabeled sample rate was 1.12%. The annual and 30-day wrong-blood-in-tube aggregate rates were both 0.04%. Patient first name, last name, and unique identification number were required on the sample by more than 90% of participating institutions; however, other requirements varied more widely. CONCLUSIONS: The rates of mislabeled samples and wrong blood in tube for US participants in this study were comparable to those reported for most European countries. The survey of patient identification and sample labeling practices and sample acceptance policies for ABO typing samples revealed both practice uniformity and variability as well as significant opportunity for improvement.