Anne Leach, Kristin J Murphy, Mandana Godard, Matthew Schwartz, Lori J Sokoll
{"title":"Proficiency Testing Customization in Clinical Trials: How the pSMILE Project Ensures High-Quality Proficiency Testing Coverage for International Laboratories.","authors":"Anne Leach, Kristin J Murphy, Mandana Godard, Matthew Schwartz, Lori J Sokoll","doi":"10.1093/jalm/jfae050","DOIUrl":"https://doi.org/10.1093/jalm/jfae050","url":null,"abstract":"","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jonathan J Tucci, Raeshun T Glover, Joesph R Wiencek
{"title":"A Pregnant Patient with a Positive Hepatitis C Antibody.","authors":"Jonathan J Tucci, Raeshun T Glover, Joesph R Wiencek","doi":"10.1093/jalm/jfae015","DOIUrl":"10.1093/jalm/jfae015","url":null,"abstract":"","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140319508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: Screening for Primary Aldosteronism by Mass Spectrometry Versus Immunoassay Measurements of Aldosterone: A Prospective Within-Patient Study.","authors":"","doi":"10.1093/jalm/jfae041","DOIUrl":"10.1093/jalm/jfae041","url":null,"abstract":"","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carlos Castillo Pérez, Laura Rodríguez Alonso, Marta Cebrián Ballesteros, Blanca Torrubia, M J Torrejón
{"title":"Persistent Mild Increase of Human Chorionic Gonadotropin in a Male Patient with Testicular Pain.","authors":"Carlos Castillo Pérez, Laura Rodríguez Alonso, Marta Cebrián Ballesteros, Blanca Torrubia, M J Torrejón","doi":"10.1093/jalm/jfae042","DOIUrl":"10.1093/jalm/jfae042","url":null,"abstract":"","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141307081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Breaking the Chain: Navigating the Pitfalls of Total Laboratory Automation.","authors":"Joe M El-Khoury","doi":"10.1093/jalm/jfae061","DOIUrl":"10.1093/jalm/jfae061","url":null,"abstract":"","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inappropriate Laboratory Testing: The Hidden Cost to the Environment-Time for a Database of Associated Costs.","authors":"Timothy F Lang","doi":"10.1093/jalm/jfae043","DOIUrl":"10.1093/jalm/jfae043","url":null,"abstract":"","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141082347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Caroline J Waddell, Gerald J Pellegrini, Neela Persad, Thomas D Filardo, Namrata Prasad, William C Carson, Terese Navarra, Michael B Townsend, Panayampalli S Satheshkumar, David Lowe, Deborah Borne, Nnenna Okoye, Julia Janssen, Anamaría Bejarano, Emily Mosites, Grace E Marx
Background: People experiencing homelessness (PEH) are underrepresented in public health and clinical research. Study methods that can improve participation by this group are needed.
Methods: In late 2022, the Centers for Disease Control and Prevention conducted an mpox serological survey using venipuncture among PEH in San Francisco, California. Blood collection by a minimally invasive device was offered if venipuncture was not possible or preferred. Participants who had a successful blood draw using the device were asked about device acceptability.
Results: Of the 209 successful blood collections, 137 (66%) were among participants who underwent venipuncture and 72 (34%) were among participants who used the device. Use of the device increased overall blood collection participation by 53%. Participants reported high acceptability and preference for the device over venipuncture.
Conclusions: Minimally invasive blood collection devices may increase participation and representation of PEH in serosurveys.
{"title":"Minimally Invasive Blood Collection for an Mpox Serosurvey among People Experiencing Homelessness.","authors":"Caroline J Waddell, Gerald J Pellegrini, Neela Persad, Thomas D Filardo, Namrata Prasad, William C Carson, Terese Navarra, Michael B Townsend, Panayampalli S Satheshkumar, David Lowe, Deborah Borne, Nnenna Okoye, Julia Janssen, Anamaría Bejarano, Emily Mosites, Grace E Marx","doi":"10.1093/jalm/jfae035","DOIUrl":"10.1093/jalm/jfae035","url":null,"abstract":"<p><strong>Background: </strong>People experiencing homelessness (PEH) are underrepresented in public health and clinical research. Study methods that can improve participation by this group are needed.</p><p><strong>Methods: </strong>In late 2022, the Centers for Disease Control and Prevention conducted an mpox serological survey using venipuncture among PEH in San Francisco, California. Blood collection by a minimally invasive device was offered if venipuncture was not possible or preferred. Participants who had a successful blood draw using the device were asked about device acceptability.</p><p><strong>Results: </strong>Of the 209 successful blood collections, 137 (66%) were among participants who underwent venipuncture and 72 (34%) were among participants who used the device. Use of the device increased overall blood collection participation by 53%. Participants reported high acceptability and preference for the device over venipuncture.</p><p><strong>Conclusions: </strong>Minimally invasive blood collection devices may increase participation and representation of PEH in serosurveys.</p>","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: To evaluate diagnostic tests for low prevalence conditions, classification accuracy metrics such as sensitivity, specificity, and positive likelihood ratio (PLR) and negative likelihood ratio (NLR) are advantageous because they are prevalence-independent and thus estimable in studies enriched for the condition. However, classification accuracy goals are often chosen without a clear understanding of whether they are clinically meaningful. Pennello (2021) proposed a risk stratification framework for determining classification accuracy goals. A software application is needed to determine the goals and provide data analysis.
Methods: We introduce DxGoals, a freely available, R-Shiny software application for determining, visualizing, and analyzing classification accuracy goals for diagnostic tests. Given prevalence p for the target condition and specification that a test's positive and negative predictive values PPVand NPV=1-cNPV should satisfy PPV>PPV* and cNPV
Results: We illustrate DxGoals on tests for penicillin allergy, ovarian cancer, and cervical cancer. The inputs cNPV*,p, and PPV* were informed by clinical management guidelines.
Conclusions: DxGoals facilitates determination, visualization, and analysis of clinically meaningful standalone and comparative classification accuracy goals. It is a potentially useful tool for diagnostic test evaluation.
{"title":"DxGoals: A Software Tool for Determining and Analyzing Clinically Meaningful Classification Accuracy Goals for Diagnostic Tests.","authors":"Ngoc-Ty Nguyen, Gene A Pennello","doi":"10.1093/jalm/jfae054","DOIUrl":"https://doi.org/10.1093/jalm/jfae054","url":null,"abstract":"<p><strong>Background: </strong>To evaluate diagnostic tests for low prevalence conditions, classification accuracy metrics such as sensitivity, specificity, and positive likelihood ratio (PLR) and negative likelihood ratio (NLR) are advantageous because they are prevalence-independent and thus estimable in studies enriched for the condition. However, classification accuracy goals are often chosen without a clear understanding of whether they are clinically meaningful. Pennello (2021) proposed a risk stratification framework for determining classification accuracy goals. A software application is needed to determine the goals and provide data analysis.</p><p><strong>Methods: </strong>We introduce DxGoals, a freely available, R-Shiny software application for determining, visualizing, and analyzing classification accuracy goals for diagnostic tests. Given prevalence p for the target condition and specification that a test's positive and negative predictive values PPVand NPV=1-cNPV should satisfy PPV>PPV* and cNPV<cNPV*, DxGoals uses Bayes Theorem to determine equivalent goals for PLR and NLR and implied goals for sensitivity and specificity. When study data are provided, DxGoals analyzes whether the determined goals are met with statistical significance. When comparing 2 tests, DxGoals translates a superiority or noninferiority goals for the differences PPV-p and p-cNPV to equivalent goals for PLR and NLR and analyzes the goals when data are provided.</p><p><strong>Results: </strong>We illustrate DxGoals on tests for penicillin allergy, ovarian cancer, and cervical cancer. The inputs cNPV*,p, and PPV* were informed by clinical management guidelines.</p><p><strong>Conclusions: </strong>DxGoals facilitates determination, visualization, and analysis of clinically meaningful standalone and comparative classification accuracy goals. It is a potentially useful tool for diagnostic test evaluation.</p>","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mark Griffiths, Pow Lee Cheng, Xiao Yan Wang, Randal Schneider, Vathany Kulasingam
Background: The objective of this study was to compare The Binding Site's Freelite on Optilite and Diazyme's Kappa/Lambda free light chains (K/L FLC) on Abbott Architect c8000 with healthy and renal insufficient populations and to evaluate their respective reference intervals for serum free light chains (sFLCs).
Methods: Two hundred sixty serum samples were measured for creatinine and sFLCs by both assays and a subset by immunofixation electrophoresis. Verification of manufacturer-defined reference intervals was assessed.
Results: Kappa free light chains (KFLC) showed excellent correlation of 0.998 R2 with a slope of 0.73. For Lambda free light chains (LFLC), an acceptable correlation of 0.953 R2 was found with a slope of 1.50 as well as a skewness-based difference with a -12.70 intercept. Healthy estimated glomerular filtration rate (eGFR) ≥60 reference interval verification of central 95% could not be confirmed for either Freelite or Diazyme although LFLC was much closer than KFLC for both assays with Freelite KFLC recovering only 37% of values within reference interval claims. The K/L FLC ratio did not meet 100% claim for both Freelite (91%) and Diazyme (95%) among those with eGFR ≥60. Samples with eGFR ≤59 had increasingly higher levels of KFLC and LFLC for both assays. When comparing worsening eGFR status, Freelite recovered increasingly higher ratios while Diazyme recovered increasingly lower ratios.
Conclusions: Healthy reference intervals could not be verified for either Freelite or Diazyme. Renal reference intervals for Freelite are currently warranted while they are not recommended for Diazyme. The differences between these 2 assays can be minimized by standardization efforts such as recalibration.
{"title":"Comparison of 2 Serum Free Light Chain Assays with Creatinine Normal and Abnormal Populations Demonstrates the Need for Standardization.","authors":"Mark Griffiths, Pow Lee Cheng, Xiao Yan Wang, Randal Schneider, Vathany Kulasingam","doi":"10.1093/jalm/jfae065","DOIUrl":"10.1093/jalm/jfae065","url":null,"abstract":"<p><strong>Background: </strong>The objective of this study was to compare The Binding Site's Freelite on Optilite and Diazyme's Kappa/Lambda free light chains (K/L FLC) on Abbott Architect c8000 with healthy and renal insufficient populations and to evaluate their respective reference intervals for serum free light chains (sFLCs).</p><p><strong>Methods: </strong>Two hundred sixty serum samples were measured for creatinine and sFLCs by both assays and a subset by immunofixation electrophoresis. Verification of manufacturer-defined reference intervals was assessed.</p><p><strong>Results: </strong>Kappa free light chains (KFLC) showed excellent correlation of 0.998 R2 with a slope of 0.73. For Lambda free light chains (LFLC), an acceptable correlation of 0.953 R2 was found with a slope of 1.50 as well as a skewness-based difference with a -12.70 intercept. Healthy estimated glomerular filtration rate (eGFR) ≥60 reference interval verification of central 95% could not be confirmed for either Freelite or Diazyme although LFLC was much closer than KFLC for both assays with Freelite KFLC recovering only 37% of values within reference interval claims. The K/L FLC ratio did not meet 100% claim for both Freelite (91%) and Diazyme (95%) among those with eGFR ≥60. Samples with eGFR ≤59 had increasingly higher levels of KFLC and LFLC for both assays. When comparing worsening eGFR status, Freelite recovered increasingly higher ratios while Diazyme recovered increasingly lower ratios.</p><p><strong>Conclusions: </strong>Healthy reference intervals could not be verified for either Freelite or Diazyme. Renal reference intervals for Freelite are currently warranted while they are not recommended for Diazyme. The differences between these 2 assays can be minimized by standardization efforts such as recalibration.</p>","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wim H M Vroemen, Ellen J S Denessen, William P T M van Doorn, Kelly E J M Pelzer, Tilman M Hackeng, Elisabeth J R Litjens, Yvonne M C Henskens, Frank M van der Sande, Will K W H Wodzig, Jeroen P Kooman, Otto Bekers, Douwe de Boer, Alma M A Mingels
Background: Cardiac troponin T (cTnT) is key in diagnosing myocardial infarction (MI) but is also elevated in end-stage renal disease (ESRD) patients. Specific larger cTnT proteoforms were identified for the acute phase of MI, while in serum of ESRD patients solely small cTnT fragments were found. However, others allocated this to a pre-analytic effect due to abundant thrombin generation in serum. Therefore, we investigated the effect of various anticoagulation methods on cTnT composition and concentration and compared the cTnT composition of MI and ESRD patients.
Methods: The agreement of cTnT concentrations between simultaneously collected serum, lithium-heparin (LH) plasma, and ethylenediaminetetraacetic acid (EDTA) plasma was studied using the high-sensitivity (hs-)cTnT immunoassay. cTnT proteoform composition was investigated in a standardized time-dependent manner through spike experiments and in simultaneously collected blood matrixes of MI and ESRD patients.
Results: Excellent hs-cTnT concentration agreements were observed across all blood matrixes (slopes > 0.98; 95% CI, 0.96-1.04). Time-dependent degradation (40 kDa intact:29 kDa fragment:15 to 18 kDa fragments) was found in LH plasma and EDTA plasma, and serum in ratios (%) of 90:10:0, 0:5:95, and 0:0:100, respectively (48 h after blood collection). Moreover, gel filtration chromatography (GFC) profiles illustrated mainly larger cTnT proteoforms in MI patients, while in ESRD patients mainly 15 to 18 kDa fragments were found for all matrices.
Conclusions: The extent of cTnT degradation in vitro is dependent on the (anti)coagulation method, without impacting hs-cTnT concentrations. Furthermore, mainly larger cTnT proteoforms were present in MI patients, while in ESRD patients mainly small 15 to 18 kDa cTnT fragments were found. These insights are essential when developing a novel hs-cTnT assay targeting larger cTnT proteoforms.
{"title":"Differences in Cardiac Troponin T Composition in Myocardial Infarction and End-Stage Renal Disease Patients: A Blood Tube Effect?","authors":"Wim H M Vroemen, Ellen J S Denessen, William P T M van Doorn, Kelly E J M Pelzer, Tilman M Hackeng, Elisabeth J R Litjens, Yvonne M C Henskens, Frank M van der Sande, Will K W H Wodzig, Jeroen P Kooman, Otto Bekers, Douwe de Boer, Alma M A Mingels","doi":"10.1093/jalm/jfae052","DOIUrl":"10.1093/jalm/jfae052","url":null,"abstract":"<p><strong>Background: </strong>Cardiac troponin T (cTnT) is key in diagnosing myocardial infarction (MI) but is also elevated in end-stage renal disease (ESRD) patients. Specific larger cTnT proteoforms were identified for the acute phase of MI, while in serum of ESRD patients solely small cTnT fragments were found. However, others allocated this to a pre-analytic effect due to abundant thrombin generation in serum. Therefore, we investigated the effect of various anticoagulation methods on cTnT composition and concentration and compared the cTnT composition of MI and ESRD patients.</p><p><strong>Methods: </strong>The agreement of cTnT concentrations between simultaneously collected serum, lithium-heparin (LH) plasma, and ethylenediaminetetraacetic acid (EDTA) plasma was studied using the high-sensitivity (hs-)cTnT immunoassay. cTnT proteoform composition was investigated in a standardized time-dependent manner through spike experiments and in simultaneously collected blood matrixes of MI and ESRD patients.</p><p><strong>Results: </strong>Excellent hs-cTnT concentration agreements were observed across all blood matrixes (slopes > 0.98; 95% CI, 0.96-1.04). Time-dependent degradation (40 kDa intact:29 kDa fragment:15 to 18 kDa fragments) was found in LH plasma and EDTA plasma, and serum in ratios (%) of 90:10:0, 0:5:95, and 0:0:100, respectively (48 h after blood collection). Moreover, gel filtration chromatography (GFC) profiles illustrated mainly larger cTnT proteoforms in MI patients, while in ESRD patients mainly 15 to 18 kDa fragments were found for all matrices.</p><p><strong>Conclusions: </strong>The extent of cTnT degradation in vitro is dependent on the (anti)coagulation method, without impacting hs-cTnT concentrations. Furthermore, mainly larger cTnT proteoforms were present in MI patients, while in ESRD patients mainly small 15 to 18 kDa cTnT fragments were found. These insights are essential when developing a novel hs-cTnT assay targeting larger cTnT proteoforms.</p>","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}