Rainbow phlebotomy collection and urine aliquots for emergency department add-on testing in the era of pandemic-driven supply shortages.

BACKGROUND: Rainbow blood draws for add-on testing in the emergency department (ED) are a common practice at our institution. We sought to determine the prevalence of this practice among reference laboratory clients and characterize the impact of pandemic-driven supply shortages. METHODS: This cross-sectional study surveyed 354 client laboratories to understand specimen collection practices in specific clinical environments and how these practices may have been affected by supply chain shortages. Data analysis by descriptive statistics was performed in Qualtrics. RESULTS: A total of 138 laboratories took the survey (39% response rate) with 57% indicating that their ED performed rainbow draws. Of these, 16% have a formal policy regarding rainbow draws, and 76% of respondents indicated that their institution was required to modify practices due to pandemic-driven supply shortages. A total of 19% indicated they routinely collect multiple urine aliquots for add-on testing. CONCLUSION: Rainbow draws and collection of urine aliquots in the ED for add-on testing are relatively common practices, with few institutions maintaining formal policies regarding the practice. Pandemic-driven supply chain shortages affected a majority of respondent laboratories and local cost-benefit analysis regarding extra specimen collection is recommended to limit waste of laboratory resources.

Spirited away: Can ethanol testing in add-on orders provide meaningful results?

Ethanol is a volatile substance, and specimens need to be tightly capped prior to analysis to prevent evaporative loss. However, add-on requests in previously decapped tubes are commonly received, yet ethanol stability in this setting is unclear. We compared the stability of ethanol in capped vs decapped tubes in the context of routine laboratory automation, storage time, and specimen volumes. Serum specimens were pooled and spiked with ethanol followed by simulating an add-on scenario. Additionally, to evaluate ethanol stability at room temperature for extended times, ethanol concentrations were measured in capped or decapped tubes containing 0.5 mL or 0.1 mL samples over a 4 h time course. Finally, the risk of misclassification of ethanol results in decapped tubes was evaluated near the critical value threshold (∼54 mmol/L). The add-on tubes had a mean recovery of 101.5 % (95 % CI: 97.7-105.4 %) relative to the direct tubes. The time-course experiment showed an average recovery of 87.4 % (95 % CI: 81.8-94.0 %) at the 4 h time point in decapped 0.5 mL specimens. An average recovery of 85.4 % (95 % CI: 84.2-86.1 %) was observed for specimens spiked near the critical value threshold. Importantly, all measurements with 0.5 mL specimen volume were within 25 %, which is the total allowable error (TAE) of the assay.However, with a 0.1 mL volume, specimens cross the TAE threshold just after 1 h, and the percent recovery at 4 h dropped to 52.9 % (95 % CI: 50.2-55.7 %). In conclusion, ethanol testing in decapped tubes remains within the TAE for up to 4 h in specimens with a 0.5 mL volume. Therefore, add-on ethanol testing using routine laboratory automation and storage conditions can be successfully performed.

Reported Awareness and Adoption of 2021 Estimated Glomerular Filtration Rate Equations Among US Clinical Laboratories, March 2022.

This study includes clinical laboratories that participated in the first general chemistry proficiency testing survey in 2022 to assess awareness and adoption of new equations from the Chronic Kidney Disease Epidemiology Collaboration for estimated glomerular filtration rate (eGFR) that eliminated race-adjustment factors, including one based on creatinine and one based on creatinine and cystatin C.

The effect of the Covid-19 shutdown on glycemic testing and control.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused a halt to in-person ambulatory care. We evaluated how the reduction in access to care affected HbA1c testing and patient HbA1c levels. METHODS: HbA1c data from 11 institutions were extracted to compare testing volume and the percentage of abnormal results between a pre-pandemic period (January-June 2019, period 1) and a portion of the COVID-19 pandemic period (Jan-June 2020, period 2). HbA1c results greater than 6.4% were categorized as abnormal. RESULTS: HbA1C testing volumes decreased in March, April and May by 23, 61 and 40% relative to the corresponding months in 2019. The percentage of abnormal results increased in April, May and June (25, 23, 9%). On average, we found that the frequency of abnormal results increased by 0.31% for every 1% decrease in testing volume (p < 0.0005). CONCLUSION: HbA1c testing volume for outpatients decreased by up to 70% during the early months of the pandemic. The decrease in testing was associated with an increase in abnormal HbA1c results.

Side-Effects of COVID-19 on Patient Care: An INR Story.

BACKGROUND: Numerous studies have documented reduced access to patient care due to the COVID-19 pandemic, including access to diagnostic or screening tests, prescription medications, and treatment for an ongoing condition. In the context of clinical management for venous thromboembolism, this could result in suboptimal therapy with warfarin. We aimed to determine the impact of the pandemic on utilization of International Normalized Ratio (INR) testing and the percentage of high and low results. METHODS: INR data from 11 institutions were extracted to compare testing volume and the percentage of INR results ≥3.5 and ≤1.5 between a pre-pandemic period (January-June 2019, period 1) and a portion of the COVID-19 pandemic period (January-June 2020, period 2). The analysis was performed for inpatient and outpatient cohorts. RESULTS: Testing volumes showed relatively little change in January and February, followed by a significant decrease in March, April, and May, and then returned to baseline in June. Outpatient testing showed a larger percentage decrease in testing volume compared to inpatient testing. At 10 of the 11 study sites, we observed an increase in the percentage of abnormal high INR results as test volumes decreased, primarily among outpatients. CONCLUSION: The COVID-19 pandemic impacted INR testing among outpatients which may be attributable to several factors. Increased supratherapeutic INR results during the pandemic period when there was reduced laboratory utilization and access to care is concerning because of the risk of adverse bleeding events in this group of patients. This could be mitigated in the future by offering drive-through testing and/or widespread implementation of home INR monitoring.

Performance Characteristics of BinaxNOW COVID-19 Antigen Card for Screening Asymptomatic Individuals in a University Setting.

We compared the performance of the Abbott BinaxNOW COVID-19 antigen card to that of a standard reverse transcription-PCR (RT-PCR) assay (Thermo Fisher TaqPath COVID-19 Combo kit) for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2,645 asymptomatic students presenting for screening at the University of Utah. SARS-CoV-2 RNA was detected in 1.7% of the study participants by RT-PCR. BinaxNOW identified 24 infections but missed 21 infections that were detected by RT-PCR. The analytical sensitivity (positive agreement) and analytical specificity (negative agreement) for the BinaxNOW were 53.3% and 100%, respectively, compared to the RT-PCR assay. The median cycle threshold (CT ) value in the specimens that had concordant positive BinaxNOW antigen results was significantly lower than that of specimens that were discordant (CT of 17.6 versus 29.6; P < 0.001). In individuals with presumably high viral loads (CT of <23.0), a 95.8% positive agreement was observed between the RT-PCR assay and BinaxNOW. Due to the possibility of false-negative results, caution must be taken when utilizing rapid antigen testing for screening asymptomatic individuals.

Reliability of Total Nucleated Cell Counts in the Setting of Hip Arthroplasty.

BACKGROUND: Total nucleated cell (TNC) count and differential are used to classify joint effusions as inflammatory or noninflammatory. Further diagnostic evaluation and management is contingent on this classification. TNC count can be measured by automated analyzers or by manual assessment using a hemocytometer. Studies have raised concerns regarding the accuracy of TNC counts measured by automated instruments, particularly in the setting of joint arthroplasty. The objective of this study was to determine whether metallosis, a complication of total hip arthroplasty in which metal debris accumulates in periprosthetic tissues and synovial fluid, is associated with inaccurate TNC counts in synovial fluid. METHODS: We compared the accuracy of cell counts measured by the Sysmex XN-1000 and Beckman Coulter Iris iQ200 with the gold standard of manual assessment using a hemocytometer in synovial fluid from patients with suspected metallosis and in fluid obtained from controls from patients with native joints and a history of arthroplasty for other indications. RESULTS: TNC counts produced by automated analyzers were associated with increased levels of discordance (relative to manual counts) in patients with metallosis. Metallosis was not associated with increased levels of discordance for RBC counts or WBC differentials. The Sysmex XN flagged all but 1 metallosis sample for manual verification of the results. CONCLUSIONS: Automated methods are generally reliable for analysis of synovial fluid. TNC counts can be inaccurate in the context of metallosis following total hip arthroplasty. Laboratories should correlate automated cell counts with a microscopic assessment of the specimen, as recommended by instrument manufacturers.

D-Dimer Varies Widely Across Instrument Platforms and is Not a Reliable Indicator of Periprosthetic Joint Infections.

The D-dimer test is a component of the modified scoring criteria for periprosthetic joint infection (PJI). The performance of the D-dimer test varies greatly among laboratories because of the lack of standardization. Laboratories may use different assays and will produce widely varying results for the same sample. This study used published proficiency testing data from 3903 laboratories to demonstrate the variability in D-dimer results and estimate the misclassification rate of patients using the proposed cutoff for the test as a component of PJI criteria. Given the variability in D-dimer results, a clinically significant percentage of patients are likely to be misclassified. The data illustrate that a universal cutoff for this marker in the context of assessment for PJI is not appropriate. Each site must conduct a study to determine an appropriate cutoff for their unique testing platform.

The costs and benefits of cross-level quality control rules.

BACKGROUND: Quality is often monitored by multi-rule schemes that are applied at each level of QC material. Cross Level (CL) quality control rules have been proposed but have not been investigated. METHODS: We used computer simulation to study the impact of CL rules on time to detection and the false positive rate in a system using multirules (3-1s, 2-2s, 4-1s, and 10x) with 2 levels of QC material We also studied the effect of correlation between shifts at each level. The performance of QC policies was compared using simulation analysis. We also compared the detection rates of QC policies (with and without QC rules) using laboratory QC data. RESULTS: Implementing the CL rule increased the false positive rate and increased the detection rate for small shifts (around 1 standard deviation). CL rules had a greater impact when the correlation of shifts between levels was high. CONCLUSIONS: CL rules have the potential to increase detection rates, but also increase false positive rates. It is difficult to identify the circumstances where the benefits of increased detection outweigh the costs of false positives. Alternative approaches to QC should be explored.

An Analysis of Multirules for Monitoring Assay Quality Control.

BACKGROUND: Multirules are often employed to monitor quality control (QC). The performance of multirules is usually determined by simulation and is difficult to predict. Previous studies have not provided computer code that would enable one to experiment with multirules. It would be helpful for analysts to have computer code to analyze rule performance. OBJECTIVE: To provide code to calculate power curves and to investigate certain properties of multirule QC. METHODS: We developed computer code in the R language to simulate multirule performance. Using simulation, we studied the incremental performance of each rule and determined the average run length and time to signal. RESULTS: We provide R code for simulating multirule performance. We also provide a Microsoft Excel spreadsheet with a tabulation of results that can be used to create power curves. We found that the R4S and 10x rules add very little power to a multirule set designed to detect shifts in the mean. CONCLUSION: QC analysts should consider using a limited-rule set.

Detection and Quantification of FLT3 Internal Tandem Duplication Mutations Do Not Vary Significantly Between Whole Blood and Blast-Enriched Samples.

OBJECTIVES: Many commonly used FLT3 mutational assay protocols require a tedious blast enrichment step. We investigated whether elimination of this step would still give equivalent results and compared the accuracy of variant allele fraction (VAF) between polymerase chain reaction/capillary electrophoresis (PCR/CE) vs next-generation sequencing (NGS) methods. METHODS: Total leukocyte vs blast-enriched whole-blood aliquots were tested for FLT3 internal tandem duplication (ITD) and tyrosine kinase domain mutations by PCR/CE. VAF of the ITD mutations was also compared with NGS VAF. RESULTS: Blast-enriched vs total leukocyte specimens showed 100% concordance in the 25 positive specimens. VAF was consistently lower by NGS, with poorer fidelity to PCR/CE VAF as the ITD size increased. CONCLUSIONS: Our study supports elimination of the blast enrichment step without compromising results or sensitivity. In addition, since NGS shows a loose correlation with PCR/CE quantitative results, NGS VAF should not be reported for FLT3 ITDs.

Quality control optimization part I: Metrics for evaluating predictive performance of quality control.

BACKGROUND: Quality control (QC) policies are usually designed using power curves. This type of analysis reasons from a cause (a shift in the assay results) to an effect (a signal from the QC monitoring process). End users face a different problem: they must reason from an effect (QC signal) to a cause. It would be helpful to have metrics that evaluated QC policies from an end-user perspective. METHODS: We developed a simple dichotomous model based on classification of assay errors. Errors are classified as important or unimportant based on a critical shift size, defined as Sc. Using this scheme, we show how QC policies can be analyzed using common accuracy metrics such as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). We explore the impact of design choices (QC limits, number of repeats) on these performance measures in a number of different contexts. RESULTS: PPV varies widely (1% to 100%) depending on context. NPV also varies (40% to 100%) but is less sensitive to context than PPV. There are many contexts in which QC policies have low predictive values. In such cases, performance (PPV, NPV) can be improved by adjusting the QC limits or the number of repeats at each QC event. CONCLUSION: The effectiveness of QC can be improved by considering the context in which the QC policy will be applied. Using simple assumptions, common accuracy metrics can be used to evaluate QC policy performance.

Estimating the cost of quality of errors in the analytical phase.

BACKGROUND: Cost of quality (COQ) can be defined as the difference between the current cost of providing laboratory services and the cost that would be incurred if there were no errors in the measurement process. Errors due to analytical imprecision and bias are not traditionally included in COQ. The objective of this study was to develop methods to estimate the COQ due to errors in the analytical phase. METHODS: We consider 2 types of error events: errors in patient results and run failures due to violation of a quality control (QC) rule. We provide a general and a simplified model for estimating the cost of analytical errors in patient results and a separate model for estimating costs due to QC failures. RESULTS: An example calculation is provided. The COQ for 12 mass spectrometry assays using the simplified cost model for estimating analytical errors and the cost model for run failures is presented. CONCLUSIONS: The models provide a way to estimate COQ associated with analytical error, which have not been previously incorporated into clinical laboratory standards or published literature. Estimating COQ and using those data to prioritize improvement efforts can be challenging for laboratories but are important for value-driven patient care.

Quality control optimization part II: A method to optimize the accuracy of laboratory quality control.

BACKGROUND: Quality control (QC) can be viewed as a diagnostic test that is used to determine whether an assay is in statistical control. Using this framework, QC performance can be evaluated using familiar metrics associated with diagnostic tests. QC plan parameters can be adjusted to optimize performance metrics. METHODS: We developed a simple dichotomous model based on classification of assay errors. Errors are classified as important or unimportant based on a critical shift size, defined as Sc. Using this scheme, we show how QC policies can be analyzed using common accuracy metrics such as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). We conducted computer experiments to determine the QC plan that optimizes QC accuracy under a wide range of scenarios. RESULTS: In general, traditional QC plans (based on2 or 3 standard deviation limits) are approximately 90% as accurate as optimized QC limits in the scenarios that were tested. There are special circumstances when traditional QC plans do not perform well. CONCLUSION: QC performance can be optimized for specific contexts.

Combined Pathology-Driven Algorithmic Testing and Integrated Reporting for Bone Marrow Examination.

CONTEXT.­: The College of American Pathologists published guideline recommending bone marrow synoptic reporting for hematologic neoplasms. OBJECTIVE.­: To evaluate the impact of pathology-driven algorithmic testing (PDAT) with integrated reporting for bone marrow examination on test utilization, ability to render a specific World Health Organization diagnosis, and clinician satisfaction 1 year after implementation. DESIGN.­: We reviewed the hematopathology reports, integrated synoptic reports, and ancillary test results generated during a 12-month period. The initial diagnosis from the hematopathology report was compared with the final diagnosis on the integrated synoptic reports. Test utilization data were compared with a previous year in which ancillary testing was ordered at clinician discretion. Clinicians were anonymously surveyed to assess their satisfaction with PDAT and integrated reporting. RESULTS.­: Integrated reporting resulted in a World Health Organization diagnosis for 80 of 85 cases (94%) compared with 54 (64%) for the hematopathology report alone. Unnecessary testing decreased from 45% pre-PDAT (124 of 274 cases) to 0.7% PDAT (2 of 268 cases), and PDAT resulted in fewer omissions of necessary tests. Clinicians preferred PDAT and valued integrated reporting for a variety of reasons, including the ease of finding relevant prognostic information. CONCLUSIONS.­: Pathology-driven algorithmic testing with integrated reporting improves the pathologist's ability to render a specific World Health Organization diagnosis and improves test utilization. Clinicians prefer PDAT to clinician-ordered testing. This is the first study to examine how synoptic reporting can modify hematologic diagnoses.

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.

Adoption of Evidence-Based Medicine in Clinical Laboratory Science: A Survey of the Prevalence of Systematic and Narrative Reviews.

BACKGROUND: Systematic reviews (SRs) play a critical role in evidence-based medicine. OBJECTIVE: To determine the publication trends of SRs in clinical laboratory science (CLS). METHODS: We searched Scopus to identify all reviews published in the top 20 CLS journals during the past 10 years (2008-2017). We determined year of publication, review type (systematic vs narrative), citations, and whether the review was accompanied by a meta-analysis (MA). RESULTS: We identified 2934 reviews. Of these, 2833 (96.6%) were narrative reviews, and 98 (3.3%) were SRs. A total of 67 (66.3%) of the SRs were accompanied by a MA. Three journals accounted for 68 of 98 (69.4%) SRs. The percentage of SRs (relative to all reviews) has increased during the past decade (P = .01). SRs were more frequently published in high-impact journals (P <.001). CONCLUSION: The publication rate of SRs in CLS journals has increased during the past decade.