A. Murali, F. Guyette, C. Martin-Gill, Marion Jones, M. Kravetsky, Sarah E. Wheeler
Abstract Objectives Ventilator management in prehospital settings using end-tidal CO2 can lead to inappropriate ventilation in the absence of point of care blood gas (POCBG) measurements. Implementation of POCBG testing in helicopter Emergency Medical Services (HEMS) is limited in part because of concern for preanalytical and analytical errors due to altitude, vibration, and other associated environmental factors and due to insufficient documentation of implementation challenges. Methods We performed accuracy and precision verification studies using standard materials tested pre-, in-, and post-flight (n=10) in a large HEMS agency. Quality assurance error log data were extracted and summarized for common POCBG errors during the first 31 months of use and air medical transport personnel were surveyed regarding POCBG use (n=63). Results No clinically significant differences were found between pre-, in-, and post-flight blood gas measurements. Error log data demonstrated a reduction in device errors over time. Survey participants found troubleshooting device errors and learning new clinical processes to be the largest barriers to implementation. Continued challenges for participants coincided with error log data including temperature and sampling difficulties. Survey participants indicated that POCBG testing improved patient management. Conclusions POCBG testing does not appear to be compromised by the HEMS environment. Temperature excursions can be reduced by use of insulated transport bags with heating and cooling packs. Availability of POCBG results in air medical transport appeared to improve ventilator management, increase recognition of ventilation-perfusion mismatch, and improve patient tolerance of ventilation.
{"title":"Implementation and challenges of portable blood gas measurements in air medical transport","authors":"A. Murali, F. Guyette, C. Martin-Gill, Marion Jones, M. Kravetsky, Sarah E. Wheeler","doi":"10.1515/cclm-2022-0011","DOIUrl":"https://doi.org/10.1515/cclm-2022-0011","url":null,"abstract":"Abstract Objectives Ventilator management in prehospital settings using end-tidal CO2 can lead to inappropriate ventilation in the absence of point of care blood gas (POCBG) measurements. Implementation of POCBG testing in helicopter Emergency Medical Services (HEMS) is limited in part because of concern for preanalytical and analytical errors due to altitude, vibration, and other associated environmental factors and due to insufficient documentation of implementation challenges. Methods We performed accuracy and precision verification studies using standard materials tested pre-, in-, and post-flight (n=10) in a large HEMS agency. Quality assurance error log data were extracted and summarized for common POCBG errors during the first 31 months of use and air medical transport personnel were surveyed regarding POCBG use (n=63). Results No clinically significant differences were found between pre-, in-, and post-flight blood gas measurements. Error log data demonstrated a reduction in device errors over time. Survey participants found troubleshooting device errors and learning new clinical processes to be the largest barriers to implementation. Continued challenges for participants coincided with error log data including temperature and sampling difficulties. Survey participants indicated that POCBG testing improved patient management. Conclusions POCBG testing does not appear to be compromised by the HEMS environment. Temperature excursions can be reduced by use of insulated transport bags with heating and cooling packs. Availability of POCBG results in air medical transport appeared to improve ventilator management, increase recognition of ventilation-perfusion mismatch, and improve patient tolerance of ventilation.","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":"5 1","pages":"859 - 866"},"PeriodicalIF":0.0,"publicationDate":"2022-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82188534","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}
Pub Date : 2022-04-01DOI: 10.1515/cclm-2022-frontmatter5
{"title":"Frontmatter","authors":"","doi":"10.1515/cclm-2022-frontmatter5","DOIUrl":"https://doi.org/10.1515/cclm-2022-frontmatter5","url":null,"abstract":"","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91293231","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 This tutorial gives an introduction into statistical methods for diagnostic medicine. The validity of a diagnostic test can be assessed using sensitivity and specificity which are defined for a binary diagnostic test with known reference or gold standard. As an example we use Procalcitonin with a cut off value ≥ 0.5 g/L as a test and Sepsis-2 criteria as a reference standard for the diagnosis of sepsis. Next likelihood ratios are introduced which combine the information given by sensitivity and specificity. For these measures the construction of confidence intervals is demonstrated. Then, we introduce predictive values using Bayes’ theorem. Predictive values are sometimes difficult to communicate. This can be improved using natural frequencies which are applied to our example. Procalcitonin is actually a continuous biomarker, hence we introduce the use of receiver operator curves (ROC) and the area under the curve (AUC). Finally we discuss sample size estimation for diagnostic studies. In order to show how to apply these concepts in practice we explain how to use the freely available software R.
本教程介绍了诊断医学的统计方法。诊断测试的有效性可以用已知参考或金标准的二元诊断测试定义的敏感性和特异性来评估。以降钙素原(cut off value≥0.5 g/L)为例，以脓毒症-2标准作为脓毒症诊断的参考标准。接下来，引入了似然比，它结合了灵敏度和特异性给出的信息。对于这些测度，给出了置信区间的构造方法。然后，利用贝叶斯定理引入预测值。预测值有时很难传达。这可以使用应用于我们的例子的固有频率来改善。降钙素原实际上是一个连续的生物标志物，因此我们引入了接收算子曲线(ROC)和曲线下面积(AUC)的使用。最后我们讨论了诊断研究的样本量估计。为了展示如何在实践中应用这些概念，我们解释了如何使用免费的软件R。
{"title":"Statistics in diagnostic medicine","authors":"P. Schlattmann","doi":"10.1515/cclm-2022-0225","DOIUrl":"https://doi.org/10.1515/cclm-2022-0225","url":null,"abstract":"Abstract This tutorial gives an introduction into statistical methods for diagnostic medicine. The validity of a diagnostic test can be assessed using sensitivity and specificity which are defined for a binary diagnostic test with known reference or gold standard. As an example we use Procalcitonin with a cut off value ≥ 0.5 g/L as a test and Sepsis-2 criteria as a reference standard for the diagnosis of sepsis. Next likelihood ratios are introduced which combine the information given by sensitivity and specificity. For these measures the construction of confidence intervals is demonstrated. Then, we introduce predictive values using Bayes’ theorem. Predictive values are sometimes difficult to communicate. This can be improved using natural frequencies which are applied to our example. Procalcitonin is actually a continuous biomarker, hence we introduce the use of receiver operator curves (ROC) and the area under the curve (AUC). Finally we discuss sample size estimation for diagnostic studies. In order to show how to apply these concepts in practice we explain how to use the freely available software R.","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":"36 1","pages":"801 - 807"},"PeriodicalIF":0.0,"publicationDate":"2022-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77067035","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. Huf, Mike Mohns, Zoe Bünning, Rebecca Lister, T. Garmatiuk, C. Buchta, Brigitte Ettl
Abstract Objectives Medical laboratory performance is a relative concept, as are quality and safety in medicine. Therefore, repetitive benchmarking appears to be essential for sustainable improvement in health care. The general idea in this approach is to establish a reference level, upon which improvement may be strived for and quantified. While the laboratory community traditionally is highly aware of the need for laboratory performance and public scrutiny is more intense than ever due to the SARS-CoV-2 pandemic, few initiatives span the globe. The aim of this study was to establish a good practice approach towards benchmarking on a high abstraction level for three key dimensions of medical laboratory performance, generate a tentative snapshot of the current state of the art in the region of Europe, Middle East, and Africa (EMEA), and thus set the stage for global follow-up studies. Methods The questionnaire used and previously published in this initiative consisted of 50 items, roughly half relating to laboratory operations in general with the other half addressing more specific topics. An international sample of laboratories from EMEA was approached to elicit high fidelity responses with the help of trained professionals. Individual item results were analyzed using standard descriptive statistics. Dimensional reduction of specific items was performed using exploratory factor analysis and assessed with confirmatory factor analysis, resulting in individual laboratory scores for the three subscales of “Operational performance”, “Integrated clinical care performance”, and “Financial sustainability”. Results Altogether, 773 laboratories participated in the survey, of which 484 were government hospital laboratories, 129 private hospital laboratories, 146 commercial laboratories, and 14 were other types of laboratories (e.g. research laboratories). Respondents indicated the need for digitalization (e.g. use of IT for order management, auto-validation), automation (e.g. pre-analytics, automated sample transportation), and establishment of formal quality management systems (e.g. ISO 15189, ISO 9001) as well as sustainably embedding them in the fabric of laboratory operations. Considerable room for growth also exists for services provided to physicians, such as “Diagnostic pathways guidance”, “Proactive consultation on complex cases”, and “Real time decision support” which were provided by less than two thirds of laboratories. Concordantly, the most important kind of turn-around time (TAT) for clinicians, sample-to-result TAT, was monitored by only 40% of respondents. Conclusions Altogether, the need for stronger integration of laboratories into the clinical care process became apparent and should be a main trajectory of future laboratory management. Factor analysis confirmed the theoretical constructs of the questionnaire design phase, resulting in a reasonably valid tool for further benchmarking activities on the three aimed-for key dimensions.
{"title":"Benchmarking medical laboratory performance: survey validation and results for Europe, Middle East, and Africa","authors":"W. Huf, Mike Mohns, Zoe Bünning, Rebecca Lister, T. Garmatiuk, C. Buchta, Brigitte Ettl","doi":"10.1515/cclm-2021-1349","DOIUrl":"https://doi.org/10.1515/cclm-2021-1349","url":null,"abstract":"Abstract Objectives Medical laboratory performance is a relative concept, as are quality and safety in medicine. Therefore, repetitive benchmarking appears to be essential for sustainable improvement in health care. The general idea in this approach is to establish a reference level, upon which improvement may be strived for and quantified. While the laboratory community traditionally is highly aware of the need for laboratory performance and public scrutiny is more intense than ever due to the SARS-CoV-2 pandemic, few initiatives span the globe. The aim of this study was to establish a good practice approach towards benchmarking on a high abstraction level for three key dimensions of medical laboratory performance, generate a tentative snapshot of the current state of the art in the region of Europe, Middle East, and Africa (EMEA), and thus set the stage for global follow-up studies. Methods The questionnaire used and previously published in this initiative consisted of 50 items, roughly half relating to laboratory operations in general with the other half addressing more specific topics. An international sample of laboratories from EMEA was approached to elicit high fidelity responses with the help of trained professionals. Individual item results were analyzed using standard descriptive statistics. Dimensional reduction of specific items was performed using exploratory factor analysis and assessed with confirmatory factor analysis, resulting in individual laboratory scores for the three subscales of “Operational performance”, “Integrated clinical care performance”, and “Financial sustainability”. Results Altogether, 773 laboratories participated in the survey, of which 484 were government hospital laboratories, 129 private hospital laboratories, 146 commercial laboratories, and 14 were other types of laboratories (e.g. research laboratories). Respondents indicated the need for digitalization (e.g. use of IT for order management, auto-validation), automation (e.g. pre-analytics, automated sample transportation), and establishment of formal quality management systems (e.g. ISO 15189, ISO 9001) as well as sustainably embedding them in the fabric of laboratory operations. Considerable room for growth also exists for services provided to physicians, such as “Diagnostic pathways guidance”, “Proactive consultation on complex cases”, and “Real time decision support” which were provided by less than two thirds of laboratories. Concordantly, the most important kind of turn-around time (TAT) for clinicians, sample-to-result TAT, was monitored by only 40% of respondents. Conclusions Altogether, the need for stronger integration of laboratories into the clinical care process became apparent and should be a main trajectory of future laboratory management. Factor analysis confirmed the theoretical constructs of the questionnaire design phase, resulting in a reasonably valid tool for further benchmarking activities on the three aimed-for key dimensions.","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":"15 1","pages":"830 - 841"},"PeriodicalIF":0.0,"publicationDate":"2022-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82829382","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 Immunoassays are currently the methods of choice for the measurement of a large panel of complex and heterogenous molecules owing to full automation, short turnaround time, high specificity and sensitivity. Despite remarkable performances, immunoassays are prone to several types of interferences that may lead to harmful consequences for the patient (e.g., prescription of an inadequate treatment, delayed diagnosis, unnecessary invasive investigations). A systematic search is only performed for some interferences because of its impracticality in clinical laboratories as it would notably impact budget, turnaround time, and human resources. Therefore, a case-by-case approach is generally preferred when facing an aberrant result. Hereby, we review the current knowledge on immunoassay interferences and present an algorithm for interference workup in clinical laboratories, from suspecting their presence to using the appropriate tests to identify them. We propose an approach to rationalize the attitude of laboratory specialists when faced with a potential interference and emphasize the importance of their collaboration with clinicians and manufacturers to ensure future improvements.
{"title":"Interferences in immunoassays: review and practical algorithm","authors":"L. Wauthier, M. Plebani, J. Favresse","doi":"10.1515/cclm-2021-1288","DOIUrl":"https://doi.org/10.1515/cclm-2021-1288","url":null,"abstract":"Abstract Immunoassays are currently the methods of choice for the measurement of a large panel of complex and heterogenous molecules owing to full automation, short turnaround time, high specificity and sensitivity. Despite remarkable performances, immunoassays are prone to several types of interferences that may lead to harmful consequences for the patient (e.g., prescription of an inadequate treatment, delayed diagnosis, unnecessary invasive investigations). A systematic search is only performed for some interferences because of its impracticality in clinical laboratories as it would notably impact budget, turnaround time, and human resources. Therefore, a case-by-case approach is generally preferred when facing an aberrant result. Hereby, we review the current knowledge on immunoassay interferences and present an algorithm for interference workup in clinical laboratories, from suspecting their presence to using the appropriate tests to identify them. We propose an approach to rationalize the attitude of laboratory specialists when faced with a potential interference and emphasize the importance of their collaboration with clinicians and manufacturers to ensure future improvements.","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":"11 1","pages":"808 - 820"},"PeriodicalIF":0.0,"publicationDate":"2022-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79479576","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}
G. Salvagno, B. Henry, L. Pighi, S. De Nitto, Gianluca Gianfilippi, G. Lippi
Abstract Objectives We provide here an updated analysis of an ongoing serosurveillance study, presenting data on the effect of a third dose of Pfizer/BioNTech BNT162b2 vaccine on serum anti-SARS-CoV-2 IgG antibodies. Methods We tested baseline SARS-CoV-2 seronegative healthcare workers undergoing primary vaccination with the mRNA-based COVID-19 Comirnaty vaccine, followed by administration of homologous vaccine booster (third dose). Venous blood was collected before either dose of primary vaccination, at 1, 3 and 6 months afterwards, as well as before and 1 month after receiving the vaccine booster. The serum concentration of anti-SARS-CoV-2 IgG was assayed with DiaSorin Trimeric spike IgG immunoassay. Results The final study population included 53 SARS-CoV-2 seronegative healthcare workers (median age 46 years; 60% females). A first peak of anti-SARS-CoV-2 spike trimeric IgG values was reached 1 month after completing primary vaccination, after which the levels gradually declined until before receiving the vaccine booster. A second peak of anti-SARS-CoV-2 spike trimeric IgG concentration was observed 1 month after receiving the vaccine booster dose (8,700 kBAU/L), which was 39-fold higher than before receiving the vaccine booster (221 kBAU/L; p<0.001), but was also nearly threefold higher compared to values seen at the first peak (2,990 kBAU/L; p<0.001). The rate of subjects with protective anti-SARS-CoV-2 spike trimeric IgG values (i.e., >264 kBAU/L) increased from 47.2% to 100% after 1 month from vaccine booster. Conclusions These results support current policies fostering COVID-19 vaccine boosters to reinforce humoral immunity against SARS-CoV-2.
{"title":"Effect of BNT162b2 booster dose on anti-SARS-CoV-2 spike trimeric IgG antibodies in seronegative individuals","authors":"G. Salvagno, B. Henry, L. Pighi, S. De Nitto, Gianluca Gianfilippi, G. Lippi","doi":"10.1515/cclm-2022-0212","DOIUrl":"https://doi.org/10.1515/cclm-2022-0212","url":null,"abstract":"Abstract Objectives We provide here an updated analysis of an ongoing serosurveillance study, presenting data on the effect of a third dose of Pfizer/BioNTech BNT162b2 vaccine on serum anti-SARS-CoV-2 IgG antibodies. Methods We tested baseline SARS-CoV-2 seronegative healthcare workers undergoing primary vaccination with the mRNA-based COVID-19 Comirnaty vaccine, followed by administration of homologous vaccine booster (third dose). Venous blood was collected before either dose of primary vaccination, at 1, 3 and 6 months afterwards, as well as before and 1 month after receiving the vaccine booster. The serum concentration of anti-SARS-CoV-2 IgG was assayed with DiaSorin Trimeric spike IgG immunoassay. Results The final study population included 53 SARS-CoV-2 seronegative healthcare workers (median age 46 years; 60% females). A first peak of anti-SARS-CoV-2 spike trimeric IgG values was reached 1 month after completing primary vaccination, after which the levels gradually declined until before receiving the vaccine booster. A second peak of anti-SARS-CoV-2 spike trimeric IgG concentration was observed 1 month after receiving the vaccine booster dose (8,700 kBAU/L), which was 39-fold higher than before receiving the vaccine booster (221 kBAU/L; p<0.001), but was also nearly threefold higher compared to values seen at the first peak (2,990 kBAU/L; p<0.001). The rate of subjects with protective anti-SARS-CoV-2 spike trimeric IgG values (i.e., >264 kBAU/L) increased from 47.2% to 100% after 1 month from vaccine booster. Conclusions These results support current policies fostering COVID-19 vaccine boosters to reinforce humoral immunity against SARS-CoV-2.","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":"56 1","pages":"930 - 933"},"PeriodicalIF":0.0,"publicationDate":"2022-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85247251","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}
L. Wieten, J. Damoiseaux, Bram Lestrade, L. Bakker‐Jonges
{"title":"Diagnostic performance characteristics of the Quanta Flash Rheumatoid Factor assay in a consecutive Dutch patient cohort","authors":"L. Wieten, J. Damoiseaux, Bram Lestrade, L. Bakker‐Jonges","doi":"10.1515/cclm-2022-0101","DOIUrl":"https://doi.org/10.1515/cclm-2022-0101","url":null,"abstract":"","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":"42 1","pages":"e142 - e145"},"PeriodicalIF":0.0,"publicationDate":"2022-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80169316","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}
Ayato Yamada, N. Hattori, Takeshi Matsuda, Norito Nishiyama, A. Shimatsu
{"title":"Clearance of macro-TSH from the circulation is slower than TSH","authors":"Ayato Yamada, N. Hattori, Takeshi Matsuda, Norito Nishiyama, A. Shimatsu","doi":"10.1515/cclm-2022-0131","DOIUrl":"https://doi.org/10.1515/cclm-2022-0131","url":null,"abstract":"","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":"98 1","pages":"e132 - e135"},"PeriodicalIF":0.0,"publicationDate":"2022-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91141157","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}
We read with interest the recent article of Ren et al. [1], who described the accuracy of an ultrasensitive electrochemiluminescence immunoassay for saliva-based Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) nucleocapsid protein (N) detection based on the S-PLEX platform (S-PLEX SARS-CoV-2 N Kit; Meso Scale Discovery, Rockville, MD, United States). This method has been specifically developed for detecting and quantifying the SARS-CoV-2 N antigen in a variety of human specimens, including serum, plasma, saliva and nasopharyngeal swabs (NPS). Briefly, either S-PLEX 96-Well SECTOR or QuickPlex plates coated with streptavidin for binding biotin-conjugated capture anti-SARS-CoV-2 N antibodies are challenged with human samples. After this step, “TURBO-BOOST”-labeled detection antibodies react with the N antigen bound to the solid phase and, after addiction of a specific reagent, an electrochemiluminescent signal is generated and read by the specific instrument. The signal produced is proportional to the concentration of N antigen present in the test sample. A preliminary evaluation of this assay revealed that the limit of detection is 0.16 pg/mL, with a diagnostic threshold set at 0.32 pg/mL and a total imprecision ranging between 7.0 and 7.7% [2]. The sample volume is only 25 μL, with total turnaround time between 4–5 h. Since this novel technique displayed remarkable diagnostic performance in saliva samples in the hands of Ren and colleagues, exhibiting up to 100% specificity with 92% sensitivity [1], we provide here a critical literature review and pooled analysis of studies which addressed the accuracy of S-PLEX SARS-CoV-2 N Kit for diagnosing acute SARS-CoV-2 infections. We carried out a digital search in the two scientific databases Medline (PubMed interface) and Scopus, using the following keywords: “S-PLEX” AND “COVID-19” OR “SARS-CoV-2”, without no language or date (i.e., up to February 17, 2022) restrictions. The initial screening of documents was conducted by G.L. and M.M., aimed at selecting studies were the diagnostic accuracy of S-PLEX SARS-CoV-2 N Kit was assessed against a reference molecular technique for diagnosing acute SARS-CoV-2 infections, and with sufficient extrapolable information for construction of a 2×2 table. A pooled analysis, based on the Mantel-Haenszel method and random effects model, was employed for estimating the diagnostic sensitivity, specificity and accuracy (reported as Summary Receiver Operating Characteristic Curve [SROC] and agreement) of this method. The inter-study heterogeneity was also assessed with χ test and I statistic. The statistical analysis was performed with Meta-DiSc 1.4 (Unit of Clinical Biostatistics team of the Ramón y Cajal Hospital, Madrid, Spain) [3]. The analysis was carried out in accordance with the Declaration of Helsinki and within the terms of Martina Montagnana and Mario Plebani share senior authorship of this work.
我们饶有兴趣地阅读了Ren等人最近的一篇文章[1]，他们描述了基于S-PLEX平台(S-PLEX SARS-CoV-2 N Kit;中尺度发现，洛克维尔，马里兰州，美国)。该方法专门用于检测和定量血清、血浆、唾液和鼻咽拭子等多种人体标本中的SARS-CoV-2 N抗原。简单地说，将S-PLEX 96-Well SECTOR或涂有链亲和素的QuickPlex板用于结合生物素偶联捕获的抗sars - cov - 2n抗体，用人类样本进行挑战。在这一步之后，“TURBO-BOOST”标记的检测抗体与固相结合的N抗原反应，在特定试剂成瘾后，产生电化学发光信号并由特定仪器读取。产生的信号与测试样品中存在的N抗原浓度成正比。对该方法的初步评估显示，检测限为0.16 pg/mL，诊断阈值设定为0.32 pg/mL，总不精密度范围为7.0至7.7%[2]。样品体积仅为25 μL，总周转时间在4-5小时之间。由于这项新技术在Ren及其同事手中的唾液样本中显示出出色的诊断性能，具有高达100%的特异性和92%的灵敏度[1]，我们在这里提供了一篇重要的文献综述和研究汇总分析，这些研究解决了S-PLEX SARS-CoV-2 N Kit诊断急性SARS-CoV-2感染的准确性。我们在两个科学数据库Medline (PubMed界面)和Scopus中进行了数字检索，使用以下关键词:“S-PLEX”和“COVID-19”或“SARS-CoV-2”，不受语言或日期(即截至2022年2月17日)的限制。文件的初步筛选由G.L.和m.m.进行，目的是选择研究，根据诊断急性SARS-CoV-2感染的参考分子技术评估S-PLEX SARS-CoV-2 N Kit的诊断准确性，并提供足够的可推断信息以构建2×2表。采用Mantel-Haenszel方法和随机效应模型进行汇总分析，评估该方法的诊断敏感性、特异性和准确性(报告为总受者工作特征曲线[SROC]和一致性)。采用χ检验和I统计量评估研究间异质性。采用Meta-DiSc 1.4(西班牙马德里Ramón y Cajal医院临床生物统计学组)进行统计分析[3]。这项分析是根据《赫尔辛基宣言》进行的，并在Martina Montagnana和Mario Plebani共同担任这项工作的高级作者的条件下进行的。
{"title":"Diagnostic accuracy of the ultrasensitive S-PLEX SARS-CoV-2 N electrochemiluminescence immunoassay","authors":"G. Lippi, B. Henry, M. Montagnana, M. Plebani","doi":"10.1515/cclm-2022-0155","DOIUrl":"https://doi.org/10.1515/cclm-2022-0155","url":null,"abstract":"We read with interest the recent article of Ren et al. [1], who described the accuracy of an ultrasensitive electrochemiluminescence immunoassay for saliva-based Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) nucleocapsid protein (N) detection based on the S-PLEX platform (S-PLEX SARS-CoV-2 N Kit; Meso Scale Discovery, Rockville, MD, United States). This method has been specifically developed for detecting and quantifying the SARS-CoV-2 N antigen in a variety of human specimens, including serum, plasma, saliva and nasopharyngeal swabs (NPS). Briefly, either S-PLEX 96-Well SECTOR or QuickPlex plates coated with streptavidin for binding biotin-conjugated capture anti-SARS-CoV-2 N antibodies are challenged with human samples. After this step, “TURBO-BOOST”-labeled detection antibodies react with the N antigen bound to the solid phase and, after addiction of a specific reagent, an electrochemiluminescent signal is generated and read by the specific instrument. The signal produced is proportional to the concentration of N antigen present in the test sample. A preliminary evaluation of this assay revealed that the limit of detection is 0.16 pg/mL, with a diagnostic threshold set at 0.32 pg/mL and a total imprecision ranging between 7.0 and 7.7% [2]. The sample volume is only 25 μL, with total turnaround time between 4–5 h. Since this novel technique displayed remarkable diagnostic performance in saliva samples in the hands of Ren and colleagues, exhibiting up to 100% specificity with 92% sensitivity [1], we provide here a critical literature review and pooled analysis of studies which addressed the accuracy of S-PLEX SARS-CoV-2 N Kit for diagnosing acute SARS-CoV-2 infections. We carried out a digital search in the two scientific databases Medline (PubMed interface) and Scopus, using the following keywords: “S-PLEX” AND “COVID-19” OR “SARS-CoV-2”, without no language or date (i.e., up to February 17, 2022) restrictions. The initial screening of documents was conducted by G.L. and M.M., aimed at selecting studies were the diagnostic accuracy of S-PLEX SARS-CoV-2 N Kit was assessed against a reference molecular technique for diagnosing acute SARS-CoV-2 infections, and with sufficient extrapolable information for construction of a 2×2 table. A pooled analysis, based on the Mantel-Haenszel method and random effects model, was employed for estimating the diagnostic sensitivity, specificity and accuracy (reported as Summary Receiver Operating Characteristic Curve [SROC] and agreement) of this method. The inter-study heterogeneity was also assessed with χ test and I statistic. The statistical analysis was performed with Meta-DiSc 1.4 (Unit of Clinical Biostatistics team of the Ramón y Cajal Hospital, Madrid, Spain) [3]. The analysis was carried out in accordance with the Declaration of Helsinki and within the terms of Martina Montagnana and Mario Plebani share senior authorship of this work.","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":"26 1","pages":"e121 - e124"},"PeriodicalIF":0.0,"publicationDate":"2022-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81848395","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 The National Institute for Health and Care Excellence recommends faecal calprotectin (f-cal) to help differentiate inflammatory bowel diseases from irritable bowel syndrome. Faecal samples for calprotectin have historically been collected at home by patients into screw-top pots and sent to laboratories where calprotectin is extracted and analysed. Faecal haemoglobin (f-Hb) samples are collected at home into specific collection devices containing stabilising buffer. We evaluated the OC-FCa method for f-cal, developed by Eiken Chemical Co., Ltd. (Japan) that uses the same collection device and analyser as f-Hb. Methods OC-FCa was assessed for limit of blank (LOB), limit of detection (LOD), limit of quantification (LOQ), within and between-run imprecision, linearity, prozone, recovery and carryover. A method comparison against the BÜHLMANN fCAL® turbo (BÜHLMANN Laboratories AG, Switzerland) was performed using patient samples and EQA. Results The LOB was 3 µg calprotectin/g faeces (µg/g), LOD 8 μg/g and LOQ 20 μg/g. Within and between-run imprecision was <5%; linearity was good (R2 > 0.99); prozone was appropriately detected; recovery was 99.6%; no observed carryover. OC-FCa showed a strong positive bias compared with BÜHLMANN fCAL® turbo (Z=−5.3587, p < 0.001). When categorised using our local pathway, which interprets calprotectin concentrations and need for further investigation, Cohen’s Kappa demonstrates substantial agreement at <50 μg/g (κ=0.80) and >150 μg/g (κ=0.63) and fair agreement (κ=0.22) in the borderline category 50–150 μg/g. Conclusions The OC-FCa method performed well in the evaluation. With the lack of standardisation for f-cal a clinical study is required to evaluate the positive bias and establish suitable cut-off levels.
{"title":"Evaluation of a faecal calprotectin method using the OC-SENSOR PLEDIA","authors":"S. O’Driscoll, C. Piggott, S. Benton","doi":"10.1515/cclm-2022-0126","DOIUrl":"https://doi.org/10.1515/cclm-2022-0126","url":null,"abstract":"Abstract Objectives The National Institute for Health and Care Excellence recommends faecal calprotectin (f-cal) to help differentiate inflammatory bowel diseases from irritable bowel syndrome. Faecal samples for calprotectin have historically been collected at home by patients into screw-top pots and sent to laboratories where calprotectin is extracted and analysed. Faecal haemoglobin (f-Hb) samples are collected at home into specific collection devices containing stabilising buffer. We evaluated the OC-FCa method for f-cal, developed by Eiken Chemical Co., Ltd. (Japan) that uses the same collection device and analyser as f-Hb. Methods OC-FCa was assessed for limit of blank (LOB), limit of detection (LOD), limit of quantification (LOQ), within and between-run imprecision, linearity, prozone, recovery and carryover. A method comparison against the BÜHLMANN fCAL® turbo (BÜHLMANN Laboratories AG, Switzerland) was performed using patient samples and EQA. Results The LOB was 3 µg calprotectin/g faeces (µg/g), LOD 8 μg/g and LOQ 20 μg/g. Within and between-run imprecision was <5%; linearity was good (R2 > 0.99); prozone was appropriately detected; recovery was 99.6%; no observed carryover. OC-FCa showed a strong positive bias compared with BÜHLMANN fCAL® turbo (Z=−5.3587, p < 0.001). When categorised using our local pathway, which interprets calprotectin concentrations and need for further investigation, Cohen’s Kappa demonstrates substantial agreement at <50 μg/g (κ=0.80) and >150 μg/g (κ=0.63) and fair agreement (κ=0.22) in the borderline category 50–150 μg/g. Conclusions The OC-FCa method performed well in the evaluation. With the lack of standardisation for f-cal a clinical study is required to evaluate the positive bias and establish suitable cut-off levels.","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":"23 1","pages":"901 - 906"},"PeriodicalIF":0.0,"publicationDate":"2022-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87936766","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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