M. Fahie-Wilson, C. Cobbaert, A. Horvath, T. Smith
Abstract Cross reactivity with high molecular weight complexes of prolactin known as macroprolactin is a common cause of positive interference in assays for serum prolactin. All prolactin assays currently available are affected with 5–25% of results indicating hyperprolactinaemia falsely elevated due to macroprolactinaemia – hyperprolactinaemia due to macroprolactin with normal concentrations of bioactive monomeric prolactin. Macroprolactinaemia has no pathological significance but, if it is not recognised as the cause, the apparent hyperprolactinaemia can lead to clinical confusion, unnecessary further investigations, inappropriate treatment and waste of healthcare resources. Macroprolactinaemia cannot be distinguished from true hyperprolactinaemia on clinical grounds alone but can be detected by a simple laboratory test based on the precipitation of macroprolactin with polyethylene glycol. Laboratory screening of all cases of hyperprolactinaemia to exclude macroprolactinaemia has been advised as best practice but has not been implemented universally and reports of clinical confusion caused by macroprolactinaemia continue to appear in the literature. Information provided by manufacturers to users of assays for prolactin regarding interference by macroprolactin is absent or inadequate and does not comply with the European Union Regulation covering in vitro diagnostic medical devices (IVDR). As the IVDR is implemented notified bodies should insist that manufacturers of assays for serum prolactin comply with the regulations by informing users that macroprolactin is a source of interference which may have untoward clinical consequences and by providing an estimate of the magnitude of the interference and a means of detecting macroprolactinaemia. Laboratories should institute a policy for excluding macroprolactinaemia in all cases of hyperprolactinaemia.
{"title":"Interference by macroprolactin in assays for prolactin: will the In Vitro Diagnostics Regulation lead to a solution at last?","authors":"M. Fahie-Wilson, C. Cobbaert, A. Horvath, T. Smith","doi":"10.1515/cclm-2022-0460","DOIUrl":"https://doi.org/10.1515/cclm-2022-0460","url":null,"abstract":"Abstract Cross reactivity with high molecular weight complexes of prolactin known as macroprolactin is a common cause of positive interference in assays for serum prolactin. All prolactin assays currently available are affected with 5–25% of results indicating hyperprolactinaemia falsely elevated due to macroprolactinaemia – hyperprolactinaemia due to macroprolactin with normal concentrations of bioactive monomeric prolactin. Macroprolactinaemia has no pathological significance but, if it is not recognised as the cause, the apparent hyperprolactinaemia can lead to clinical confusion, unnecessary further investigations, inappropriate treatment and waste of healthcare resources. Macroprolactinaemia cannot be distinguished from true hyperprolactinaemia on clinical grounds alone but can be detected by a simple laboratory test based on the precipitation of macroprolactin with polyethylene glycol. Laboratory screening of all cases of hyperprolactinaemia to exclude macroprolactinaemia has been advised as best practice but has not been implemented universally and reports of clinical confusion caused by macroprolactinaemia continue to appear in the literature. Information provided by manufacturers to users of assays for prolactin regarding interference by macroprolactin is absent or inadequate and does not comply with the European Union Regulation covering in vitro diagnostic medical devices (IVDR). As the IVDR is implemented notified bodies should insist that manufacturers of assays for serum prolactin comply with the regulations by informing users that macroprolactin is a source of interference which may have untoward clinical consequences and by providing an estimate of the magnitude of the interference and a means of detecting macroprolactinaemia. Laboratories should institute a policy for excluding macroprolactinaemia in all cases of hyperprolactinaemia.","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":"23 1","pages":"1350 - 1355"},"PeriodicalIF":0.0,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86519722","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}
J. Cadamuro, Johannes Winzer, Lisa Perkhofer, A. von Meyer, J. M. Bauçà, O. Plekhanova, Anna‐Maria Linko‐Parvinen, J. Watine, Kathrin Maria Kniewallner, Martin H. Keppel, T. Šálek, Cornelia Mrazek, T. Felder, H. Oberkofler, E. Haschke-Becher, P. Vermeersch, A. Kristoffersen, Christoph Eisl
Abstract Objectives Although laboratory result presentation may lead to information overload and subsequent missed or delayed diagnosis, little has been done in the past to improve this post-analytical issue. We aimed to investigate the efficiency, efficacy and user satisfaction of alternative report formats. Methods We redesigned cumulative (sparkline format) and single reports (improved tabular and z-log format) and tested these on 46 physicians, nurses and medical students in comparison to the classical tabular formats, by asking standardized questions on general items on the reports as well as on suspected diagnosis and follow-up treatment or diagnostics. Results Efficacy remained at a very high level both in the new formats as well as in the classical formats. We found no significant difference in any of the groups. Efficiency improved in all groups when using the sparkline cumulative format and marginally when showing the improved tabular format. When asking medical questions, efficiency and efficacy remained similar between report formats and groups. All alternative reports were subjectively more attractive to the majority of participants. Conclusions Showing cumulative reports as a graphical display led to faster detection of general information on the report with the same level of correctness. Considering the familiarity bias of the classical single report formats, the borderline-significant improvement of the alternative tabular format and the non-inferiority of the z-log format, suggests that single reports might benefit from some improvements derived from basic information design.
{"title":"Efficiency, efficacy and subjective user satisfaction of alternative laboratory report formats. An investigation on behalf of the Working Group for Postanalytical Phase (WG-POST), of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)","authors":"J. Cadamuro, Johannes Winzer, Lisa Perkhofer, A. von Meyer, J. M. Bauçà, O. Plekhanova, Anna‐Maria Linko‐Parvinen, J. Watine, Kathrin Maria Kniewallner, Martin H. Keppel, T. Šálek, Cornelia Mrazek, T. Felder, H. Oberkofler, E. Haschke-Becher, P. Vermeersch, A. Kristoffersen, Christoph Eisl","doi":"10.1515/cclm-2022-0269","DOIUrl":"https://doi.org/10.1515/cclm-2022-0269","url":null,"abstract":"Abstract Objectives Although laboratory result presentation may lead to information overload and subsequent missed or delayed diagnosis, little has been done in the past to improve this post-analytical issue. We aimed to investigate the efficiency, efficacy and user satisfaction of alternative report formats. Methods We redesigned cumulative (sparkline format) and single reports (improved tabular and z-log format) and tested these on 46 physicians, nurses and medical students in comparison to the classical tabular formats, by asking standardized questions on general items on the reports as well as on suspected diagnosis and follow-up treatment or diagnostics. Results Efficacy remained at a very high level both in the new formats as well as in the classical formats. We found no significant difference in any of the groups. Efficiency improved in all groups when using the sparkline cumulative format and marginally when showing the improved tabular format. When asking medical questions, efficiency and efficacy remained similar between report formats and groups. All alternative reports were subjectively more attractive to the majority of participants. Conclusions Showing cumulative reports as a graphical display led to faster detection of general information on the report with the same level of correctness. Considering the familiarity bias of the classical single report formats, the borderline-significant improvement of the alternative tabular format and the non-inferiority of the z-log format, suggests that single reports might benefit from some improvements derived from basic information design.","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":"108 1","pages":"1356 - 1364"},"PeriodicalIF":0.0,"publicationDate":"2022-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77284023","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}
Riccardo Lucis, D. Poz, Monica Poletto, Liliana Puzzolante, A. Sartor, F. Curcio
{"title":"Early detection of Candida parapsilosis in peripheral blood as a result of a peripheral blood smear performed after cytographic changes on the Beckman Coulter UniCel DxH 800 hematology","authors":"Riccardo Lucis, D. Poz, Monica Poletto, Liliana Puzzolante, A. Sartor, F. Curcio","doi":"10.1515/cclm-2022-0448","DOIUrl":"https://doi.org/10.1515/cclm-2022-0448","url":null,"abstract":"","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":"5 1","pages":"e207 - e209"},"PeriodicalIF":0.0,"publicationDate":"2022-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86290541","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}
Sebastian Hörber, Christoph Drees, T. Ganzenmueller, Kristina Schmauder, S. Peter, D. Biskup, Andreas Peter
Abstract Objectives Antigen tests are an essential part of SARS-CoV-2 testing strategies. Rapid antigen tests are easy to use but less sensitive compared to nucleic acid amplification tests (NAT) and less suitable for large-scale testing. In contrast, laboratory-based antigen tests are suitable for high-throughput immunoanalyzers. Here we evaluated the diagnostic performance of the laboratory-based Siemens Healthineers SARS-CoV-2 Antigen (CoV2Ag) assay. Methods In a public test center, from 447 individuals anterior nasal swab specimens as well as nasopharyngeal swab specimens were collected. The nasal swab specimens were collected in sample inactivation medium and measured using the CoV2Ag assay. The nasopharyngeal swab specimens were measured by RT-PCR. Additionally, 9,046 swab specimens obtained for screening purposes in a tertiary care hospital were analyzed and positive CoV2Ag results confirmed by NAT. Results In total, 234/447 (52.3%) participants of the public test center were positive for SARS-CoV-2-RNA. Viral lineage B1.1.529 was dominant during the study. Sensitivity and specificity of the CoV2Ag assay were 88.5% (95%CI: 83.7–91.9%) and 99.5% (97.4–99.9%), respectively. Sensitivity increased to 93.7% (97.4–99.9%) and 98.7% (97.4–99.9%) for swab specimens with cycle threshold values <30 and <25, respectively. Out of 9,046 CoV2Ag screening tests from hospitalized patients, 21 (0.2%) swab specimens were determined as false-positive by confirmatory NAT. Conclusions Using sample tubes containing inactivation medium the laboratory-based high-throughput CoV2Ag assay is a very specific and highly sensitive assay for detection of SARS-CoV-2 antigen in nasal swab specimens including the B1.1.529 variant. In low prevalence settings confirmation of positive CoV2Ag results by SARS-CoV-2-RNA testing is recommended.
{"title":"Evaluation of a laboratory-based high-throughput SARS-CoV-2 antigen assay","authors":"Sebastian Hörber, Christoph Drees, T. Ganzenmueller, Kristina Schmauder, S. Peter, D. Biskup, Andreas Peter","doi":"10.1515/cclm-2022-0360","DOIUrl":"https://doi.org/10.1515/cclm-2022-0360","url":null,"abstract":"Abstract Objectives Antigen tests are an essential part of SARS-CoV-2 testing strategies. Rapid antigen tests are easy to use but less sensitive compared to nucleic acid amplification tests (NAT) and less suitable for large-scale testing. In contrast, laboratory-based antigen tests are suitable for high-throughput immunoanalyzers. Here we evaluated the diagnostic performance of the laboratory-based Siemens Healthineers SARS-CoV-2 Antigen (CoV2Ag) assay. Methods In a public test center, from 447 individuals anterior nasal swab specimens as well as nasopharyngeal swab specimens were collected. The nasal swab specimens were collected in sample inactivation medium and measured using the CoV2Ag assay. The nasopharyngeal swab specimens were measured by RT-PCR. Additionally, 9,046 swab specimens obtained for screening purposes in a tertiary care hospital were analyzed and positive CoV2Ag results confirmed by NAT. Results In total, 234/447 (52.3%) participants of the public test center were positive for SARS-CoV-2-RNA. Viral lineage B1.1.529 was dominant during the study. Sensitivity and specificity of the CoV2Ag assay were 88.5% (95%CI: 83.7–91.9%) and 99.5% (97.4–99.9%), respectively. Sensitivity increased to 93.7% (97.4–99.9%) and 98.7% (97.4–99.9%) for swab specimens with cycle threshold values <30 and <25, respectively. Out of 9,046 CoV2Ag screening tests from hospitalized patients, 21 (0.2%) swab specimens were determined as false-positive by confirmatory NAT. Conclusions Using sample tubes containing inactivation medium the laboratory-based high-throughput CoV2Ag assay is a very specific and highly sensitive assay for detection of SARS-CoV-2 antigen in nasal swab specimens including the B1.1.529 variant. In low prevalence settings confirmation of positive CoV2Ag results by SARS-CoV-2-RNA testing is recommended.","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":"52 1","pages":"1478 - 1485"},"PeriodicalIF":0.0,"publicationDate":"2022-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76961121","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":"Platelet phagocytosis by monocytes","authors":"M. Khedmati, M. J. Sharifi","doi":"10.1515/cclm-2022-0343","DOIUrl":"https://doi.org/10.1515/cclm-2022-0343","url":null,"abstract":"","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":"41 1","pages":"e204 - e206"},"PeriodicalIF":0.0,"publicationDate":"2022-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88731102","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}
Abstract Epidemiological and clinical studies show a causal association between serum triglyceride (TG) level, the number of triglyceride-rich lipoproteins (TRLs) and their remnants, and the increased risk of atherosclerosis and cardiovascular disease (CVD) development. In light of current guidelines for dyslipidemia management, the laboratory parameters reflecting TRL content are recommended as part of the routine lipid analysis process and used for CVD risk assessment, especially in people with hypertriglyceridemia (HTG), diabetes mellitus, obesity and low levels of low-density lipoprotein cholesterol (LDL-C), in which high residual CVD risk is observed. The basic routinely available laboratory parameters related with TRL are serum TG and non-high-density lipoprotein cholesterol (non-HDL-C) levels, but there are also other biomarkers related to TRL metabolism, the determination of which can be helpful in identifying the basis of HTG development or assessing CVD risk or can be the target of pharmacological intervention. In this review, we present the currently available laboratory parameters related to HTG. We summarise their link with TRL metabolism and HTG development, the determination methods as well as their clinical significance, the target values and interpretation of the results in relation to the current dyslipidemia guidelines.
{"title":"Hypertriglyceridemia, a causal risk factor for atherosclerosis, and its laboratory assessment","authors":"Ewa Wieczorek, Agnieszka Ćwiklińska, M. Jankowski","doi":"10.1515/cclm-2022-0189","DOIUrl":"https://doi.org/10.1515/cclm-2022-0189","url":null,"abstract":"Abstract Epidemiological and clinical studies show a causal association between serum triglyceride (TG) level, the number of triglyceride-rich lipoproteins (TRLs) and their remnants, and the increased risk of atherosclerosis and cardiovascular disease (CVD) development. In light of current guidelines for dyslipidemia management, the laboratory parameters reflecting TRL content are recommended as part of the routine lipid analysis process and used for CVD risk assessment, especially in people with hypertriglyceridemia (HTG), diabetes mellitus, obesity and low levels of low-density lipoprotein cholesterol (LDL-C), in which high residual CVD risk is observed. The basic routinely available laboratory parameters related with TRL are serum TG and non-high-density lipoprotein cholesterol (non-HDL-C) levels, but there are also other biomarkers related to TRL metabolism, the determination of which can be helpful in identifying the basis of HTG development or assessing CVD risk or can be the target of pharmacological intervention. In this review, we present the currently available laboratory parameters related to HTG. We summarise their link with TRL metabolism and HTG development, the determination methods as well as their clinical significance, the target values and interpretation of the results in relation to the current dyslipidemia guidelines.","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":"53 1","pages":"1145 - 1159"},"PeriodicalIF":0.0,"publicationDate":"2022-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76270388","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}
Abstract Objectives Accurate measurement of serum folate is essential for the diagnosis and management of various disorders. This study aims to investigate the between-method differences of four immunoassays and a rapid isotope-dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) method. Methods Roche Cobas (USA), Abbott Alinity i2000 (USA), Beckman Coulter Access (USA), Mindray CL-6000i (China), and the ID-LC-MS/MS method were compared using 46 human serum samples. The results were analysed by Passing–Bablok regressions and Bland–Altman plots. A bias of 13.31% based on biological variation was used as the bias criterion. Results All the within-run and total coefficients of variation (CVs) met the specification. The folate concentrations determined by all the assays were significantly different (p=0.0028). All assays had correlation coefficients over 0.97 with each other. The 95% confidence intervals (CIs) for the slope seldom contained 1 and few 95% CIs for the intercept contained 0 in the regression equations. Compared to ID-LC-MS/MS, the biases of all assays ranged from −20.91 to 13.56 nmol/L, and the mean relative biases ranged from −9.85 to 40.33%. The predicted mean relative biases at the medical decision levels rarely met the criterion. Conclusions Assays for serum folate had good correlations with each other but lacked good agreement. The accuracy and consistency of assays for serum folate should be measured and assessed routinely. Standardization work to improve the accuracy of serum folate assays, such as the extension of traceability to reference methods or materials, calibration standardization efforts, and assay-adjusted cut-offs should be promoted.
{"title":"Comparison of four different immunoassays and a rapid isotope-dilution liquid chromatography-tandem mass spectrometry assay for serum folate","authors":"Lizi Jin, You-li Lu, Xilian Yi, Meiwei Zhang, Jiangtao Zhang, Weiyan Zhou, J. Zeng, Tianjiao Zhang, Chuanbao Zhang","doi":"10.1515/cclm-2021-1283","DOIUrl":"https://doi.org/10.1515/cclm-2021-1283","url":null,"abstract":"Abstract Objectives Accurate measurement of serum folate is essential for the diagnosis and management of various disorders. This study aims to investigate the between-method differences of four immunoassays and a rapid isotope-dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) method. Methods Roche Cobas (USA), Abbott Alinity i2000 (USA), Beckman Coulter Access (USA), Mindray CL-6000i (China), and the ID-LC-MS/MS method were compared using 46 human serum samples. The results were analysed by Passing–Bablok regressions and Bland–Altman plots. A bias of 13.31% based on biological variation was used as the bias criterion. Results All the within-run and total coefficients of variation (CVs) met the specification. The folate concentrations determined by all the assays were significantly different (p=0.0028). All assays had correlation coefficients over 0.97 with each other. The 95% confidence intervals (CIs) for the slope seldom contained 1 and few 95% CIs for the intercept contained 0 in the regression equations. Compared to ID-LC-MS/MS, the biases of all assays ranged from −20.91 to 13.56 nmol/L, and the mean relative biases ranged from −9.85 to 40.33%. The predicted mean relative biases at the medical decision levels rarely met the criterion. Conclusions Assays for serum folate had good correlations with each other but lacked good agreement. The accuracy and consistency of assays for serum folate should be measured and assessed routinely. Standardization work to improve the accuracy of serum folate assays, such as the extension of traceability to reference methods or materials, calibration standardization efforts, and assay-adjusted cut-offs should be promoted.","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":"110 1","pages":"1393 - 1402"},"PeriodicalIF":0.0,"publicationDate":"2022-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82694459","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}
W. Coucke, C. Charlier, K. Croes, B. Mahieu, Hugo Neels, C. Stove, J. Tytgat, André Vanescote, A. Verstraete, Sarah Wille, Arnaud Capron
Abstract Objectives Fast and reliable ethanol assays analysis are used in a clinical context for patients suspected of ethanol intoxication. Mostly, automated systems using an enzymatic reaction based on ethanol dehydrogenase are used. The manuscript focusses on the evaluation of the performance of these assays. Methods Data included 30 serum samples used in the Belgian EQA scheme from 2019 to 2021 and concentrations ranged from 0.13 to 3.70 g/L. A regression line between target concentrations and reported values was calculated to evaluate outliers, bias, variability and measurement uncertainty. Results A total of 1,611 results were taken into account. Bias was the highest for Alinity c over the whole concentration range and the lowest for Vitros for low concentrations and Cobas 8000 using the c702 module for high concentrations. The Architect and Cobas c501/c502 systems showed the lowest variability over the whole concentration range. Highest variability was observed for Cobas 8000 using the 702 module, Thermo Scientific and Alinity c. Cobas 8000 using the c702 module showed the highest measurement uncertainty for lower concentrations. For higher concentrations, Alinity c, Thermo Scientific and Vitros were the methods with the highest measurement uncertainty. Conclusions The bias of the enzymatic techniques is nearly negligible for all methods except Alinity c. Variability differs strongly between measurement procedures. This study shows that the Alinity c has a worse measurement uncertainty than other systems for concentrations above 0.5 g/L. Overall, we found the differences in measurement uncertainty to be mainly influenced by the differences in variability.
{"title":"Analytical performance of eight enzymatic assays for ethanol in serum evaluated by data from the Belgian external quality assessment scheme","authors":"W. Coucke, C. Charlier, K. Croes, B. Mahieu, Hugo Neels, C. Stove, J. Tytgat, André Vanescote, A. Verstraete, Sarah Wille, Arnaud Capron","doi":"10.1515/cclm-2022-0285","DOIUrl":"https://doi.org/10.1515/cclm-2022-0285","url":null,"abstract":"Abstract Objectives Fast and reliable ethanol assays analysis are used in a clinical context for patients suspected of ethanol intoxication. Mostly, automated systems using an enzymatic reaction based on ethanol dehydrogenase are used. The manuscript focusses on the evaluation of the performance of these assays. Methods Data included 30 serum samples used in the Belgian EQA scheme from 2019 to 2021 and concentrations ranged from 0.13 to 3.70 g/L. A regression line between target concentrations and reported values was calculated to evaluate outliers, bias, variability and measurement uncertainty. Results A total of 1,611 results were taken into account. Bias was the highest for Alinity c over the whole concentration range and the lowest for Vitros for low concentrations and Cobas 8000 using the c702 module for high concentrations. The Architect and Cobas c501/c502 systems showed the lowest variability over the whole concentration range. Highest variability was observed for Cobas 8000 using the 702 module, Thermo Scientific and Alinity c. Cobas 8000 using the c702 module showed the highest measurement uncertainty for lower concentrations. For higher concentrations, Alinity c, Thermo Scientific and Vitros were the methods with the highest measurement uncertainty. Conclusions The bias of the enzymatic techniques is nearly negligible for all methods except Alinity c. Variability differs strongly between measurement procedures. This study shows that the Alinity c has a worse measurement uncertainty than other systems for concentrations above 0.5 g/L. Overall, we found the differences in measurement uncertainty to be mainly influenced by the differences in variability.","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":"77 1","pages":"1211 - 1217"},"PeriodicalIF":0.0,"publicationDate":"2022-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85730494","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}
Yuan-Jessica Zhuang, Yeukai T. M. Mangwiro, M. Wake, R. Saffery, R. Greaves
Abstract Newborn screening (NBS) programs operate in many countries, processing millions of dried bloodspot (DBS) samples annually. In addition to early identification of various adverse health outcomes, these samples have considerable potential as a resource for population-based research that could address key questions related to child health. The feasibility of archival DBS samples for emerging targeted and untargeted multi-omics analysis has not been previously explored in the literature. This review aims to critically evaluate the latest advances to identify opportunities and challenges of applying omics analyses to NBS cards in a research setting. Medline, Embase and PubMed databases were searched to identify studies utilizing DBS for genomic, proteomic and metabolomic assays. A total of 800 records were identified after removing duplicates, of which 23 records were included in this review. These papers consisted of one combined genomic/metabolomic, four genomic, three epigenomic, four proteomic and 11 metabolomic studies. Together they demonstrate that the increasing sensitivity of multi-omic analytical techniques makes the broad use of NBS samples achievable for large cohort studies. Maintaining the pre-analytical integrity of the DBS sample through storage at temperatures below −20 °C will enable this important resource to be fully realized in a research capacity.
{"title":"Multi-omics analysis from archival neonatal dried blood spots: limitations and opportunities","authors":"Yuan-Jessica Zhuang, Yeukai T. M. Mangwiro, M. Wake, R. Saffery, R. Greaves","doi":"10.1515/cclm-2022-0311","DOIUrl":"https://doi.org/10.1515/cclm-2022-0311","url":null,"abstract":"Abstract Newborn screening (NBS) programs operate in many countries, processing millions of dried bloodspot (DBS) samples annually. In addition to early identification of various adverse health outcomes, these samples have considerable potential as a resource for population-based research that could address key questions related to child health. The feasibility of archival DBS samples for emerging targeted and untargeted multi-omics analysis has not been previously explored in the literature. This review aims to critically evaluate the latest advances to identify opportunities and challenges of applying omics analyses to NBS cards in a research setting. Medline, Embase and PubMed databases were searched to identify studies utilizing DBS for genomic, proteomic and metabolomic assays. A total of 800 records were identified after removing duplicates, of which 23 records were included in this review. These papers consisted of one combined genomic/metabolomic, four genomic, three epigenomic, four proteomic and 11 metabolomic studies. Together they demonstrate that the increasing sensitivity of multi-omic analytical techniques makes the broad use of NBS samples achievable for large cohort studies. Maintaining the pre-analytical integrity of the DBS sample through storage at temperatures below −20 °C will enable this important resource to be fully realized in a research capacity.","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":"219 1","pages":"1318 - 1341"},"PeriodicalIF":0.0,"publicationDate":"2022-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75492399","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}
C. Markus, Rui Zhen Tan, Chun Yee Lim, W. Rankin, S. Matthews, T. P. Loh, W. Hague
Abstract Objectives One approach to assessing reference material (RM) commutability and agreement with clinical samples (CS) is to use ordinary least squares or Deming regression with prediction intervals. This approach assumes constant variance that may not be fulfilled by the measurement procedures. Flexible regression frameworks which relax this assumption, such as quantile regression or generalized additive models for location, scale, and shape (GAMLSS), have recently been implemented, which can model the changing variance with measurand concentration. Methods We simulated four imprecision profiles, ranging from simple constant variance to complex mixtures of constant and proportional variance, and examined the effects on commutability assessment outcomes with above four regression frameworks and varying the number of CS, data transformations and RM location relative to CS concentration. Regression framework performance was determined by the proportion of false rejections of commutability from prediction intervals or centiles across relative RM concentrations and was compared with the expected nominal probability coverage. Results In simple variance profiles (constant or proportional variance), Deming regression, without or with logarithmic transformation respectively, is the most efficient approach. In mixed variance profiles, GAMLSS with smoothing techniques are more appropriate, with consideration given to increasing the number of CS and the relative location of RM. In the case where analytical coefficients of variation profiles are U-shaped, even the more flexible regression frameworks may not be entirely suitable. Conclusions In commutability assessments, variance profiles of measurement procedures and location of RM in respect to clinical sample concentration significantly influence the false rejection rate of commutability.
{"title":"Performance of four regression frameworks with varying precision profiles in simulated reference material commutability assessment","authors":"C. Markus, Rui Zhen Tan, Chun Yee Lim, W. Rankin, S. Matthews, T. P. Loh, W. Hague","doi":"10.1515/cclm-2022-0205","DOIUrl":"https://doi.org/10.1515/cclm-2022-0205","url":null,"abstract":"Abstract Objectives One approach to assessing reference material (RM) commutability and agreement with clinical samples (CS) is to use ordinary least squares or Deming regression with prediction intervals. This approach assumes constant variance that may not be fulfilled by the measurement procedures. Flexible regression frameworks which relax this assumption, such as quantile regression or generalized additive models for location, scale, and shape (GAMLSS), have recently been implemented, which can model the changing variance with measurand concentration. Methods We simulated four imprecision profiles, ranging from simple constant variance to complex mixtures of constant and proportional variance, and examined the effects on commutability assessment outcomes with above four regression frameworks and varying the number of CS, data transformations and RM location relative to CS concentration. Regression framework performance was determined by the proportion of false rejections of commutability from prediction intervals or centiles across relative RM concentrations and was compared with the expected nominal probability coverage. Results In simple variance profiles (constant or proportional variance), Deming regression, without or with logarithmic transformation respectively, is the most efficient approach. In mixed variance profiles, GAMLSS with smoothing techniques are more appropriate, with consideration given to increasing the number of CS and the relative location of RM. In the case where analytical coefficients of variation profiles are U-shaped, even the more flexible regression frameworks may not be entirely suitable. Conclusions In commutability assessments, variance profiles of measurement procedures and location of RM in respect to clinical sample concentration significantly influence the false rejection rate of commutability.","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":"39 1","pages":"1164 - 1174"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86664536","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}
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