Assessment of Failure Risks in Laboratories During the Pandemic

2022 ◽  
pp. 230-243
Author(s):  
Antonia Mourtzikou ◽  
Marilena Stamouli ◽  
Georgia Kalliora ◽  
Panagiotis Koumpouros ◽  
Ioanna Petraki ◽  
...  
Keyword(s):  
Failure Modes ◽  
False Negative ◽  
Patient Treatment ◽  
Acid Extraction ◽  
Test Results ◽  
Negative Results ◽  
Clinical Laboratories ◽  
False Negative Results ◽  
Pcr Technology ◽  
Analytical Phase

Clinical laboratories produce test results that support the diagnosis, prognosis, and patient treatment. Test results must be relevant, accurate, and reliable for patient care. International bibliographic data estimate that approximately 62.0% of the errors made in clinical laboratories are due to errors during the pre-analytical stage. This chapter presents a failure modes and effects analysis (FMEA) to analyze potential failure risks within the pre-analytical phase and classify them according to severity and likelihood. FMEA allows molecular laboratories to lower costs and drive better outcomes through high-quality nucleic acid extraction, sensitive detection, and accurate quantification. RT-PCR technology continues to be the gold standard for the clinical detection of SARS-CoV-2 RNA in individuals suspected of COVID-19. It is essential to use highly sensitive assays to detect active infections and reduce the likelihood of false-negative results.

Application of Failure Modes and Effects Analysis (FMEA) During the Pre-analytical Phase in a Greek Biochemistry Laboratory

2019 ◽  
Vol 8 (3) ◽  
pp. 22-35 ◽  
Author(s):  
Marilena Stamouli ◽  
Antonia Mourtzikou ◽  
Petros L Karkalousos ◽  
Zoe Athanasiadou ◽  
Evaggelia Marasidi ◽  
...  
Keyword(s):  
Failure Modes ◽  
Patient Treatment ◽  
Test Results ◽  
Clinical Laboratories ◽  
Bibliographic Data ◽  
Potential Failure ◽  
Analytical Phase ◽  
Fmea Analysis ◽  
Analytical Errors ◽  
Made In

It is well known that the results from clinical laboratories support diagnosis, prognosis and patient treatment. Thus, test results must be relevant, accurate and reliable for patient care. Despite all the automation, errors that are classified as pre-analytical, analytical and post-analytical, are still present. International bibliographic data estimates that approximately 62.0% of the errors made in clinical laboratories are due to errors during the pre-analytical stage. The effect of the pre-analytical errors on the laboratory results has consequences that in many cases can lead to reduction of laboratory quality. In this study, the authors run a failure modes and effects analysis (FMEA) to analyze potential failure risks within the pre-analytical phase, in order to classify them according to severity and likelihood, based on the experience. In the present article, the authors performed an FMEA analysis of the pre-analytical phase of the testing process of a biochemistry laboratory.

scholarly journals Towards Multitarget Testing in Molecular Microbiology

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Deborah Steensels ◽  
Anne Vankeerberghen ◽  
Hans De Beenhouwer
Keyword(s):  
False Negative ◽  
Lessons Learned ◽  
Patient Treatment ◽  
Culture Methods ◽  
Diagnostic Assays ◽  
Genome Variability ◽  
Negative Results ◽  
Conventional Culture ◽  
False Negative Results ◽  
Single Target

Advantages of PCR assays over more conventional culture-based diagnostics include significantly higher sensitivities and shorter turnaround times. They are particularly useful when patient treatment has already been initiated or for specimens that may contain microorganisms that are slow-growing, difficult to culture, or for which culture methods do not exist. However, due to genome variability, single target testing might lead to false-negative results. This paper focuses on examples from our own experiences and the literature to provide insight into the limitations of single target testing in molecular biology. Lessons learned from these experiences include the careful design of diagnostic assays, preferably multitargeted, the importance of investigating the incidence and epidemiology of infection in detail, the frequent participation in appropriate quality assurance schemes, and the importance of continuous attentiveness by investigators when confronted with inconsistent results. In conclusion, multitargeted testing in microbiological molecular assays should be a rule.

scholarly journals False Covid-19 Test Results – Could We Do Things Better? A Personal Opinion

2020 ◽  
Vol 8 (5) ◽  
Author(s):  
Suzanne Lisbeth Ekelund
Keyword(s):  
False Positive ◽  
False Negative ◽  
Test Results ◽  
Negative Results ◽  
False Negative Results ◽  
Personal Opinion ◽  
Potential Problems

This paper describes the problems with false covid-19 test results, both false positive and false negative results. The problems are related to the quality of tests, test sampling and the currently limited follow-up procedures. A test and follow-up strategy that could decrease the potential problems is suggested.

scholarly journals Comparative study of Allergy Explorer (ALEX) versus ImmunoCAP platforms

2020 ◽  
Vol 17 (1) ◽  
pp. 66-84
Author(s):  
C Nerelius ◽  
M Andersson ◽  
L Sogaard ◽  
M Schwanbeck ◽  
S Kofler ◽  
...  
Keyword(s):  
Dynamic Range ◽  
False Negative ◽  
Specific Ige ◽  
Test Results ◽  
Technical Performance ◽  
Negative Results ◽  
Allergen Components ◽  
False Negative Results ◽  
Low Dynamic Range ◽  
Immunocap Isac

Objective. In this study, technical performance of the new multiplex ALEX test was compared with results from ImmunoCAP single tests (tIgE, sIgE) and the multiplex platform ImmunoCAP ISAC sIgE 112. Materials and methods. Eleven whole allergen extracts and corresponding allergen components from different allergen groups were used for the analysis of 64-66 patients’ sera by all three platforms. Results. For the whole allergens, 55% false negative results were obtained with the ALEX test comparing to the ImmunoCAP sIgE tests while for allergen components the ALEX test gives 33% false negative results when compared to ImmunoCAP sIgE test results. Additionally, the ALEX test is characterized by a low dynamic range - the platform demonstrated no results above 36 kUA/L for samples giving >100 kUA/L using ImmunoCAP Specific IgE tests in the analysis of sIgE response to the whole allergens. For the allergen components, ALEX showed no results above 38 kUA/L for samples of up to 150 kUA/L according to ImmunoCAP Specific IgE test results. Comparing to ImmunoCAP single plex tests, ALEX show low dynamic range and poor agreement in quantitative results for tIgE and sIgE both for whole allergens and allergen components, while in the comparison with ImmunoCAP ISAC sIgE 112 platform, the agreement is better, but the sensitivity and dynamic range are still low._ Conclusions. The ALEX test has some serious limitations in its performance comparing to both types of ImmunoCAP platforms.

scholarly journals Comparative study of Allergy Explorer (ALEX) versus ImmunoCAP platforms

2020 ◽  
Vol 17 (1) ◽  
pp. 66-84
Author(s):  
C Nerelius ◽  
M Andersson ◽  
L Sogaard ◽  
M Schwanbeck ◽  
S Kofler ◽  
...  
Keyword(s):  
Dynamic Range ◽  
False Negative ◽  
Specific Ige ◽  
Test Results ◽  
Technical Performance ◽  
Negative Results ◽  
Allergen Components ◽  
False Negative Results ◽  
Low Dynamic Range ◽  
Immunocap Isac

Objective. In this study, technical performance of the new multiplex ALEX test was compared with results from ImmunoCAP single tests (tIgE, sIgE) and the multiplex platform ImmunoCAP ISAC sIgE 112. Materials and methods. Eleven whole allergen extracts and corresponding allergen components from different allergen groups were used for the analysis of 64-66 patients sera by all three platforms. Results. For the whole allergens, 55% false negative results were obtained with the ALEX test comparing to the ImmunoCAP sIgE tests while for allergen components the ALEX test gives 33% false negative results when compared to ImmunoCAP sIgE test results. Additionally, the ALEX test is characterized by a low dynamic range - the platform demonstrated no results above 36 kUA/L for samples giving 100 kUA/L using ImmunoCAP Specific IgE tests in the analysis of sIgE response to the whole allergens. For the allergen components, ALEX showed no results above 38 kUA/L for samples of up to 150 kUA/L according to ImmunoCAP Specific IgE test results. Comparing to ImmunoCAP single plex tests, ALEX show low dynamic range and poor agreement in quantitative results for tIgE and sIgE both for whole allergens and allergen components, while in the comparison with ImmunoCAP ISAC sIgE 112 platform, the agreement is better, but the sensitivity and dynamic range are still low._ Conclusions. The ALEX test has some serious limitations in its performance comparing to both types of ImmunoCAP platforms.

scholarly journals Development and application of a canine endogenous internal positive control for use in real-time PCR assays

2018 ◽  
Vol 30 (5) ◽  
pp. 789-792 ◽  
Author(s):  
Joseph J. Modarelli ◽  
Pamela J. Ferro ◽  
Maria D. Esteve-Gasent
Keyword(s):  
Real Time ◽  
Real Time Pcr ◽  
False Negative ◽  
Positive Control ◽  
Acid Extraction ◽  
Nucleic Acid Extraction ◽  
Negative Results ◽  
False Negative Results ◽  
Internal Positive Control ◽  
Pcr Assays

Real-time PCR (rtPCR) tests have become a method of choice in many diagnostic settings, both animal and human. A concern remains, however, regarding rtPCR assay inhibition during nucleic acid extraction and/or rtPCR reaction process that may result in false-negative results. The use of an internal positive control, either endogenous or exogenous, to mitigate this issue has become more commonplace. We identified and standardized an endogenous internal positive control that can be utilized in rtPCR assays targeting canine-specific pathogens in either a singleplex or multiplex format. The target chosen for the endogenous internal positive control (EIPC-K9) was a highly conserved region in canine mitochondrial DNA. Samples from 240 dogs and 11 other species were screened with EIPC-K9; all canine samples were detected, and no cross-amplification with other species tested was observed. Additionally, no inhibition was noted when comparing singleplex to multiplex rtPCR formats.

scholarly journals Limitations of a Commercial Assay as Diagnostic Test of Autoimmune Encephalitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Raquel Ruiz-García ◽  
Guillermo Muñoz-Sánchez ◽  
Laura Naranjo ◽  
Mar Guasp ◽  
Lidia Sabater ◽  
...  
Keyword(s):  
False Negative ◽  
Autoimmune Encephalitis ◽  
Clinical Syndrome ◽  
The Other ◽  
Transfected Cells ◽  
Negative Results ◽  
Clinical Laboratories ◽  
False Negative Results ◽  
Number Of Patients ◽  
Separate Cohort

Detection of neuronal surface antibodies (NSAb) is important for the diagnosis of autoimmune encephalitis (AE). Although most clinical laboratories use a commercial diagnostic kit (Euroimmun, Lübeck, Germany) based on indirect immunofluorescence on transfected cells (IIFA), clinical experience suggests diagnostic limitations. Here, we assessed the performance of the commercial IIFA in serum and CSF samples of patients with suspected AE previously examined by rat brain immunohistochemistry (Cohort A). Of 6213 samples, 404 (6.5%) showed brain immunostaining suggestive of NSAb: 163 (40%) were positive by commercial IIFA and 241 (60%) were negative. When these 241 samples were re-assessed with in-house IIFA, 42 (18%) were positive: 21 (9%) had NSAb against antigens not included in the commercial IIFA and the other 21 (9%) had NSAb against antigens included in the commercial kit (false negative results). False negative results occurred more frequently with CSF (29% vs 10% in serum) and predominantly affected GABABR (39%), LGI1 (17%) and AMPAR (11%) antibodies. Results were reproduced in a separate cohort (B) of 54 AE patients with LGI1, GABABR or AMPAR antibodies in CSF which were missed in 30% by commercial IIFA. Patients with discordant GABABR antibody results (positive in-house but negative commercial IIFA) were less likely to develop full-blown clinical syndrome; no significant clinical differences were noted for the other antibodies. Overall, NSAb testing by commercial IIFA led to false negative results in a substantial number of patients, mainly those affected by anti-LG1, GABABR or AMPAR encephalitis. If these disorders are suspected and commercial IIFA is negative, more comprehensive antibody studies are recommended.

Recommendations for Validating Estrogen and Progesterone Receptor Immunohistochemistry Assays

2010 ◽  
Vol 134 (6) ◽  
pp. 930-935 ◽  
Author(s):  
Patrick L. Fitzgibbons ◽  
Douglas A. Murphy ◽  
M. Elizabeth H. Hammond ◽  
D. Craig Allred ◽  
Paul N. Valenstein
Keyword(s):  
Estrogen Receptor ◽  
Progesterone Receptor ◽  
Hormonal Therapy ◽  
False Negative ◽  
Test Results ◽  
Negative Results ◽  
False Negative Results ◽  
Technical Validation ◽  
Invasive Breast Carcinomas ◽  
Assessment Procedures

Abstract Context.—Estrogen receptor and progesterone receptor status is assessed on all newly diagnosed, invasive breast carcinomas and in recurrences to determine patient eligibility for hormonal therapy, but 10% to 20% of estrogen receptor and progesterone receptor test results are discordant when tested in multiple laboratories. Objective.—To define the analytic (technical) validation requirements for estrogen receptor and progesterone receptor immunohistochemistry assays used to select patients for hormonal therapy. Data Sources.—Literature review and expert consensus. Conclusions.—A standardized process for initial test validation is described. We believe adoption of this process will improve the accuracy of hormone-receptor testing, reduce interlaboratory variation, and minimize false-positive and false-negative results. Required ongoing assay assessment procedures are also described.

scholarly journals Negative Immunodiffusion Test Results Obtained with Sera of Paracoccidioidomycosis Patients May Be Related to Low-Avidity Immunoglobulin G2 Antibodies Directed against Carbohydrate Epitopes

2003 ◽  
Vol 10 (5) ◽  
pp. 802-807 ◽  
Author(s):  
Andréia R. Neves ◽  
Ronei L. Mamoni ◽  
Cláudio L. Rossi ◽  
Zoilo P. de Camargo ◽  
Maria Heloísa S. L. Blotta
Keyword(s):  
Paracoccidioides Brasiliensis ◽  
False Negative ◽  
Enzyme Linked Immunosorbent Assay ◽  
Test Results ◽  
Sodium Metaperiodate ◽  
Negative Results ◽  
Carbohydrate Epitopes ◽  
False Negative Results ◽  
Specific Igg

ABSTRACT Immunodiffusion (ID) is the serologic test most frequently used for the diagnosis and posttherapy follow-up of patients with paracoccidioidomycosis (PCM). The ID test is highly specific (100%), but its sensitivity is relatively low (90%), leading to false-negative results. The aim of this study was to determine the profiles of antibodies in sera from patients with proven PCM and with negative results in the ID test (IDneg) versus positive results in the ID test (IDpos). We analyzed 46 sera from patients with active PCM for total immunoglobulin G (IgG) and IgG subclass responses to Paracoccidioides brasiliensis gp43 antigen (treated or not treated with sodium metaperiodate) by enzyme-linked immunosorbent assay and immunoblotting. Immunoblotting showed that both IDneg and IDpos sera recognized predominantly the gp43 fraction of the P. brasiliensis antigen used in the ID test. IDneg sera contain low-avidity antibodies, low levels of specific IgG (total) and IgG1, and high levels of IgG2 compared with IDpos sera. The antibodies present in IDneg sera were predominantly directed against carbohydrate epitopes, since treatment with sodium metaperiodate resulted in a significant decrease in antibody reactivity. These data suggest that the lack of reactivity of sera from PCM patients in the ID test may be related to the production of low-avidity IgG2 antibodies directed against carbohydrate epitopes.

Diagnosis ofClostridium difficileassociated diarrhea: comparison of three rapid methods employing different markers for detection

1995 ◽  
Vol 41 (1) ◽  
pp. 88-91 ◽  
Author(s):  
Kathleen M. Riederer ◽  
Patrick Lawson ◽  
Marilyn S. Held ◽  
Karen Petrylka ◽  
Laurence E. Briski ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
False Negative ◽  
Latex Agglutination ◽  
Cytotoxicity Assay ◽  
Test Results ◽  
Negative Results ◽  
False Negative Results ◽  
Hands On ◽  
Rapid Tests ◽  
Clostridium Difficile Associated Diarrhea

Latex agglutination and the enzyme immunoassays Cytoclone (EIA-C) and VIDAS (EIA-V) were compared with a cytotoxicity assay for the diagnosis of Clostridium difficile associated diarrhea. Among patients with discrepant results, the cytotoxicity assay and clinical assessment were used to evaluate the performance of the latex agglutination and EIA tests. Clostridium difficile associated diarrhea was documented in 30/149 samples (20.1%) from 130 patients. All test results matched in 113 instances. Latex agglutination, EIA-C, and EIA-V yielded false positive results in 10, 4, and 7 samples and false negative results in 8, 9, and 14 samples, respectively. Latex agglutination demonstrated 87.8% efficiency compared with 91.3% for EIA-C and 85.7% for EIA-V and 3 min hands-on time compared with 4.5 min for EIA-V and 10 min for EIA-C. On the basis of these findings and given the fact that all rapid tests have their shortcomings, we believe that latex agglutination is the most practical method.Key words: Clostridium difficile, diarrhea, colitis.

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