Journal Article In Memoriam: Edward W. Bermes, Jr., PhD, FAACC (1932–2021) Get access Stephen E Kahn, Stephen E Kahn Pathology and Laboratory Medicine, Loyola University Health System—A Member of Trinity Health, Maywood, IL, USA Address correspondence to this author at: Department of Pathology and Laboratory Medicine, Loyola University of Chicago, Health Sciences Campus, Loyola Medicine, Regional Clinical Laboratory, EMS, Room 5220, 2160 South First Ave., Maywood, IL 60153. E-mail skahn@lumc.edu. https://orcid.org/0000-0001-7850-3773 Search for other works by this author on: Oxford Academic Google Scholar Jean C Joseph, Jean C Joseph JCJ Solutions, Seal Beach, CA, USA Search for other works by this author on: Oxford Academic Google Scholar Susan A Evans, Susan A Evans Bio Decisions Consulting, Los Gatos, CA, USA Search for other works by this author on: Oxford Academic Google Scholar Wendell R O’Neal Wendell R O’Neal The WHISK Group—Consultants, Cincinnati, OH, USA Search for other works by this author on: Oxford Academic Google Scholar The Journal of Applied Laboratory Medicine, Volume 8, Issue 2, March 2023, Pages 435–436, https://doi.org/10.1093/jalm/jfac138 Published: 06 March 2023 Article history Received: 18 October 2022 Accepted: 18 November 2022 Published: 06 March 2023

The ID NOW COVID-19 (IDNCOV) assay performed on the ID Now Instrument (Abbott Diagnostics, Scarborough, Inc. Scarborough, ME) is a rapid diagnostic test that can be performed in a point of care setting equivalent to CLIA waived testing.…

The ID Now COVID-19 (IDNCOV) assay performed on the ID Now instrument (Abbott Diagnostics, Inc., Scarborough, ME) is a rapid diagnostic test that can be performed in a point-of-care setting equivalent to Clinical Laboratory Improvement Amendments (CLIA)-waived testing. The assay utilizes isothermal amplification and can reportedly deliver results in approximately 5 to 13 min. As this assay could provide significant improvements to workflow in our hospital system, we sought to compare the performance of this test with our current coronavirus disease 2019 (COVID-19) assay, the Abbott RealTime SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) (ACOV) assay performed on the Abbott m2000 system (Abbott Molecular Inc., Des Plaines, IL).

Evidence-based laboratory medicine (EBLM) consists of asking a clinical question, then acquiring, appraising, and analyzing the evidence to apply the findings to address this clinical question and to be able to audit this overall process. Elements of a good clinical question include patient population, intervention, comparison, outcome, timing, and setting. To find the evidence to answer a clinical question, resources ranging from stronger study designs such as meta-analyses and systematic reviews to weaker case studies can be used to search for appropriate studies and determine the strength of the evidence. Appraisal of Guidelines for Research and Evaluation and Standards for Reporting of Diagnostic Accuracy are checklist tools used for critically appraising the evidence. Key metrics that provide objective data for evaluating laboratory tests include diagnostic accuracy, predictive value, receiver operating characteristic curves, and likelihood ratios. Taken together, all key elements of EBLM can aid in the development of clinical practice guidelines (CPGs), which are trustworthy. Resource tools have also been developed to overcome the barriers to adaptation and implementation of CPGs at the local level. EBLM continues to gain prominence in the practice of clinical laboratory medicine, particularly in the significant, but challenging, areas of addressing the quality of the evidence for optimizing laboratory test utilization and linking the results of laboratory tests to improved patient outcomes.

Major types of specimen labeling errors are associated with a small number of common causes. Specimen labeling errors have significant consequences for patient care, for healthcare management and for increasing costs that are often unaccounted for. Specimen labeling errors may be prevented by adhering to appropriate policies as well as unique educational programs, marketing strategies and other techniques.

The goals of this study were to assess the use of the I-STAT for blood creatinine measurement in oncology patients and to determine whether chemotherapy or other factors contributed to the discrepant point-of-care creatinine test results observed in specimens from patients in ambulatory oncology settings. Our studies led us to consider other possible causes of observed discrepancies beyond the effects of chemotherapeutic drugs, including lot-to-lot variation in I-STAT reagent cartridges.

From the Department of Pathology - Clinical Laboratories, Loyola University Health System, Maywood, IL. Reprints: Stephen Ellsworth Kahn, PhD, Department of Pathology - Clinical Laboratories, Loyola University Health System, 2160 South First Avenue, Maywood, IL 60153. E-mail: [email protected]. The author declares no conflict of interest.

The detection and quantification of monoclonal proteins (MCP) play an essential role in the diagnosis and management of plasma cell dyscrasias. As a follow‐up to an unusual case in which our SPEP method severely underestimated the size of an IgM monoclonal protein in a patient with a provisional diagnosis of amyloidosis, we investigated the linearity of the Sebia Hydrasys, Hydragel beta 1–2 method ( Sebia, Inc. Norcross, GA 30093) for the recovery of IgM(n=19) and IgG(n=9) MCP using the manufacturer's routine protocol both before and after pre‐dilution of the serum with saline (SAL) or a chaotropic diluent containing a mild reducing agent(DPD). MCP concentrations in SPEP patterns from amido black‐stained gels were quantitated by the routine Sebia protocol, and the recoveries of the albumin and MCP bands were directly measured as total RBG intensities by image analysis(IA) using Image Studio Lite, 4.0 (Li‐Cor, Lincoln NE 68504). Results are presented as mean (min to max). IA showed that the mean recoveries of the albumin and MCP bands of diluted samples containing IgM MCP were increased by factors of 3.0‐fold (1.6‐ to 10.6) and 4.1‐fold (1.5 to 24.6), respectively, over those measured in the undiluted samples. Moreover, the MCP/albumin recovery ratio was increased by 1.2‐fold (0.7 to 2.4) compared to the undiluted serum. This ratio was significantly increased compared to the ratio of 0.95‐fold (0.8 to 1.1) observed for the specimens that contained IgG MCP (p<0.001, KW). These results showed that the routine Sebia method, which specifies the analysis of undiluted serum, frequently under‐estimated the concentration of IgM MCP, possibly owing to flaws in the sample application and/or the protein staining steps of the procedure. Pre‐dilution with SAL prior to analysis increased IgM MCP concentrations by a mean of 9.4 % (0 to 22.0). Pre‐dilution with DPD provided similar increases except in one case in which the concentrations of two, relatively small, IgM MCP were increased by 22 and 52%. In addition to an under‐recovery of IgM MCP by SPEP, we found that band size estimates based on the quantitation of the total IgM concentration by rate nephelometry (Immage 800, Beckman Coulter Inc., Brea CA 92821) were 1.3‐ to 2.7‐fold greater than those measured by SPEP. Both of the major methods used for estimating the size of MCP appear to have analytical limitations that compromise their accuracy. While either method might be adequate for monitoring changes in tumor burden over time, the discrepancies we noted may be a source of confusion and error in scenarios in which fixed clinical decision thresholds based on MCP concentration are used as criteria for diagnosis, disease progression, and response to treatment.

PURPOSE:Screening of patients with sepsis is needed to increase recognition and allow for earlier interventions. There is no consensus on whether the addition of lactate to the critical result laboratory's call list should be a standard practice.MATERIALS AND METHODS:This was a retrospective cohort study that compared management and outcomes of patients with sepsis having lactate ≥4 mmol/L before (group 1) and after (group 2) the addition of a critical result threshold of lactate of ≥4 mmol/L to the critical result laboratory's call list and its effects on time to antibiotics and intravenous fluids (IVFs).RESULTS:One hundred twenty-one patients were included. Lactate was higher in group 1 (7.0 ± 4.3 vs 5.6 ± 2.0, P = 0.03). More patients in group 2 received hydrocortisone (1.9% vs 22.4%, P = .001). Hospital mortality, 30-day mortality, and 90-day mortality were significantly lower in group 2 (59.3% vs 32.8%, P = .003; 68.5% vs 37.3%, P ≤ .001; 68.5% vs 41.8%, P = .002). There were no significant differences in total volume of IVFs (2400.8 ± 1720.0 vs 2483.7 ± 2155.7, P = 0.83), time to start IVFs (184.0 ± 283.2 vs 115.6 ± 190.5, P = 0.27), or antibiotics (184.8 ± 187.1 vs 133.7 ± 137.4, P = 0.16).CONCLUSION:Addition of lactate to the critical result laboratory's call list did not lead to a statistically significant improvement in time to IVFs or antibiotics, although the average time to antibiotics and IVFs decreased by 51.1 and 68.4 minutes, respectively. Hospital mortality, 30-day mortality, and 90-day mortality were lower in group 2, which may be, in part, due to increased recognition of severe sepsis by critical result notification and earlier intervention.

In the US, the roles and responsibilities, as well as the education and degree requirements for laboratory directors, are well defined by the CLIA 1988 regulations and in the requirements of private and governmental accreditation bodies. Focusing on doing the right test on the right patient at the right time is nothing new for laboratory directors. But in the current healthcare environment, it is more important than ever for laboratory directors to be actively engaged in effective laboratory stewardship. One aspect of that stewardship is seeking to identify opportunities for improving laboratory test utilization and working to make productive contributions toward progress in these areas. For laboratory directors and other stakeholders, improving laboratory test utilization is a quality goal that must have a high priority. Over the past 2 decades, reports from the Institute of Medicine have progressively focused on key quality issues in healthcare including reducing medical errors, recognizing diagnostic errors, and improving patient safety. The Institute of Medicine advocates provision of healthcare that is safe, timely, efficient, effective, equitable, and patient-centered (STEEEP)2 (1). Laboratory utilization must also focus on these goals. Opportunities to improve laboratory test utilization are numerous and often complex. They can differ from one laboratory to the next, as can any resulting process improvement changes intended …

The National Academy of Clinical Biochemistry (NACB) has developed consensus-based guidelines for the laboratory evaluation and monitoring of patients with specified disorders for two decades. In 1997, the NACB recognized the need to standardize the process of guideline development and promulgated its first Standard Operating Procedure (SOP) for this purpose. In 2010, the American Association of Clinical Chemistry (AACC) and NACB created the Evidence-Based Laboratory Medicine Committee (EBLMC). Among other roles, this group was given responsibility to provide oversight of clinical practice guideline development in accordance with SOP guidance and using currently accepted good practices. In 2011, the U.S. Institute of Medicine (IOM) published two reports of relevance: 'Clinical Practice Guidelines We Can Trust' and 'Finding What Works in Health Care - Standards for Systematic Reviews.' These reports were created as part of a response to a legislative mandate from the U.S. Congress requesting that steps be taken to implement recommendations from lOM's report on 'Knowing What Works in Health Care' (2008). The latest revision of the laboratory medicine practice guidelines (LMPG) SOP was in part driven by these reports. NACB continues to develop LMPGs at a rate of roughly one per year through standard processes detailed in its 2014 revision of the SOP. This article describes the NACB and EBLMC experience in developing LMPGs with a focus on the evolution and use of the latest SOP. AACC and NACB have established a solid track record in collaboratively working with many clinical societies and professional organizations on clinical practice guideline development. Presently, three LMPG's are in various stages of development and all with the collaboration of other clinical/professional groups. The practices and tools being used for current LMPGs in progress are also highlighted in the context of the challenges that presently exist for effective clinical practice guideline development in the U.S.

The results of implementation of different clinical laboratory techniques are to be equal in clinically significant limits to be optimally applied in diagnostics of diseases and treatment of patients. When the results of laboratory tests are not standardized and harmonized for the very same clinical assay the results can be expressed by unmatched numbers. Unfortunately, in some handbooks the values are presented based on the results of application of specific laboratory techniques without considering possibility or likelihood of differences between various techniques. When this is a case, accumulation of data of diferent clinical research studies and working out of clinical handbooks on this basis will be inconsistent. Inadequate understanding of issue that the results of laboratory tests are not standardized and harmonized can lead to incorrect clinical, financial, managerial or technical decisions. The standardization of clinical laboratory techniques was applied to many measurands related to primary referent techniques (standard specimen of pure substance) or/and developed referent measurement techniques. However, harmonization of clinical laboratory techniques for those measurands which are not related any developed measurement techniques is quite problematic due to inadequate determination of measurand, its inadequate analytical specificity, insufficient attention to commutability of referent materials and poor systematic approach to harmonization. To overcome these issues an infrastructure is to be developed to support systematic approach to identification and prioritization of measurands which are to be harmonized on the basis of clinical importance and technical applicability. The management of technical implementation harmonization process for specific measurands.

To the Editor: We commend Don-Wauchope et al., who assessed 11 National Academy of Clinical Biochemistry (NACB)1 laboratory medicine practice guidelines (LMPGs) with the AGREE II (Appraisal of Guidelines for Research and Evaluation II) instrument (1), and we thank Bossuyt for his accompanying editorial (2). The results of this study are helpful but are not unexpected. These LMPGs were developed over several years. The 8 nonarchived LMPGs published in the past 5 years used 4 different systems for grading and weighting practice recommendations. One system that several LMPG committees have used is a modified US Preventive Services Task Force (USPSTF) system. A second system used for 2 LMPGs was that of the American College of Cardiology and the American Heart Association. At times, NACB LMPG committees have used clinical societies' systems when these groups are primary collaborators in LMPG development, as well as significant end users of the LMPG. A third system created by the authors of 3 LMPGs focused on tumor marker tests. This unique system was developed by LMPG members who felt that considerable heterogeneity in clinical oncology practice guidelines failed to indicate a preference in any clinical society's system. Finally, authors of the most recent diabetes …

Objectives: This is the first systematic review of the effectiveness of barcoding practices for reducing patient specimen and laboratory testing identification errors.Design and methods: The CDC-funded Laboratory Medicine Best Practices Initiative systematic review methods for quality improvement practices were used.Results: A total of 17 observational studies reporting on barcoding systems are included in the body of evidence; 10 for patient specimens and 7 for point-of-care testing. All 17 studies favored barcoding, with meta-analysis mean odds ratios for barcoding systems of 4.39 (95% CI: 3.05-6.32) and for point-of-care testing of 5.93 (95% CI: 5.28-6.67).Conclusions: Barcoding is effective for reducing patient specimen and laboratory testing identification errors in diverse hospital settings and is recommended as an evidence-based "best practice." The overall strength of evidence rating is high and the effect size rating is substantial. Unpublished studies made an important contribution comprising almost half of the body of evidence.Disclaimer: The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry (CDC/ATSDR). (C) 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Abstract Abstract 3363 Recently, several of the newer oral anticoagulants such as Rivaroxaban (Bayer Healthcare) (R) Apixaban (BMS/Pfizer) (A) and Dabigatran (Boehringer Ingleheim) (D) have been approved for different indications in the US and European countries. Although the monitoring is not required or promoted to manage the approved dosages of these drugs in different indications, population based bleeding complications with some of these agents have been reported warranting the monitoring of these drugs to optimize therapy. Conventionally the Xa based drugs such as Rivaroxaban and Apixaban are monitorable by following the anti-Xa activity whereas the dabigatran can be followed by anti-IIa activity. The pharmacokinetics of these drugs is reportedly monitored by such sophisticated methods as the liquid chromatographic – mass spectrometric methods. The conventional clotting methods such the PT/INR and APTT assays provide widely variable results which are dependent on the type of reagents used. Heptest exhibits a higher sensitivity to the anti-IIa agents in comparison to the anti-Xa agents. Prothrombinase activated clotting time (PiCT) is a Xa/IIa based clotting assay which can be performed in using a 1 stage and 2 stage method. The 1 stage method is highly sensitive to newer anticoagulants in contrast to the 2 stage PiCT and other tests. For the routine monitoring of these newer oral anticoagulant drugs a simple and rapid assay with the linear sensitivity range of 0–500 ng/ml is optimal for various patient populations. The current study is designed to determine the relative sensitivity of the one stage PiCT test in comparison to 4 PT, 4 APTT, Heptest and thrombin generation assays. Normal human pooled plasma was supplemented with R, A and D at a concentration range of 0–10 μg/ml. PT/INR analysis was carried using Thromboplasin C+, Innovin, Neoplastin and Simplastin reagents. The APTT assays were carried out using Actin FS, Actin FSL, Stago APTT and Platelin reagents. Heptest and one stage and two stage PiCT assays were also performed. All of the clot-based assays were carried out on the ACL analyzer with the exception of Heptest and PiCT tests. The thrombin generation assay was carried out using a flourogenic substrate method (Technoclone). In the PT assay, all reagents showed assay based variabilities in the clotting times and were relatively insensitive to A, however R and D produced a concentration dependent anticoagulant effect. Which were relatively insensitive at concentrations below 1 μg/ml. Similarly in the APTT assays, while R and D produced a concentration dependent anticoagulant effect all 4 reagents were relatively insensitive to A. The Actin FSL reagent was found to be sensitive to both the R and D and concentrations of less than 100 ng/ml were measurable. D produced the strongest anticoagulant effects in both the PT and APTT assays. Heptest was relatively insensitive to R and A, however at concentrations of greater than 1 μg/ml it produced concentration dependent anticoagulant effects. In the one stage PiCT assay, all agents including A prolonged the anticoagulant effect which produced a linear response at submicrogram levels and was found to be highly sensitive to D. The two stage PiCT also exhibited a linear sensitivity in the 0–100 ng/ml range. In the thrombin generation generation assay, R exhibited the strongest inhibitory effect with an IC50 of 160 ng/ml, D at 310 ng/ml and A produced a relatively weaker inhibitory effects with an IC50 >1000 ng/ml. These studies clearly demonstrate the limitations of various laboratory assays in the monitoring of newer oral anticoagulant agents with the exception of 1 stage PiCT test which can be universally used in the monitoring of these agents in the projected clinical ranges. Furthermore the one stage PiCT test can be performed in such matrices as whole blood, PRP and PPP. Moreover this test can also be carried out in point of care settings. Additional results on the assay performance and the clinical utility of some of these tests will be presented with a recommendation for the monitoring of newer oral anticoagulant drugs in such clinical settings as the extended prophylaxis of DVT and atrial fibrillation. Disclosures: No relevant conflicts of interest to declare.

Results between different clinical laboratory measurement procedures (CLMP) should be equivalent, within clinically meaningful limits, to enable optimal use of clinical guidelines for disease diagnosis and patient management. When laboratory test results are neither standardized nor harmonized, a different numeric result may be obtained for the same clinical sample. Unfortunately, some guidelines are based on test results from a specific laboratory measurement procedure without consideration of the possibility or likelihood of differences between various procedures. When this happens, aggregation of data from different clinical research investigations and development of appropriate clinical practice guidelines will be flawed. A lack of recognition that results are neither standardized nor harmonized may lead to erroneous clinical, financial, regulatory, or technical decisions. Standardization of CLMPs has been accomplished for several measurands for which primary (pure substance) reference materials exist and/or reference measurement procedures (RMPs) have been developed. However, the harmonization of clinical laboratory procedures for measurands that do not have RMPs has been problematic owing to inadequate definition of the measurand, inadequate analytical specificity for the measurand, inadequate attention to the commutability of reference materials, and lack of a systematic approach for harmonization. To address these problems, an infrastructure must be developed to enable a systematic approach for identification and prioritization of measurands to be harmonized on the basis of clinical importance and technical feasibility, and for management of the technical implementation of a harmonization process for a specific measurand.