Many studies have assessed the biological variation (BV) of cardiac-specific troponins (cTn), reporting widely varying within-subject BV (CVI) estimates. The aim of this study was to provide ...meta-analysis-derived BV estimates for troponin I (cTnI) and troponin T (cTnT) for different sampling intervals and states of health.
Relevant studies were identified by a systematic literature search. Studies were classified according to their methodological quality by the Biological Variation Data Critical Appraisal Checklist (BIVAC). Meta-analyses of BIVAC-compliant studies were performed after stratification by cTn isoform, exclusion of results below the limit of detection, states of health, and sampling interval to deliver reference change values (RCV), index of individuality (II) and analytical performance specifications (APS) for these settings.
Sixteen and 15 studies were identified for cTnI and cTnT, respectively, out of which 6 received a BIVAC grade A. Five studies had applied contemporary cTnI assays, but none contemporary cTnT. High-sensitivity (hs-) cTnI and cTnT delivered similar estimates in all settings. Long-term CVI estimates (15.1; 11.3%) derived from healthy individuals were higher than short-term (4.3%; 5.3%) for hs-cTnI and hs-cTnT, respectively, although confidence intervals overlapped. Estimates derived from diseased subjects were similar to estimates in healthy individuals for all settings.
This study provides robust estimates for hs-cTnI and hs-cTnT applicable for different clinical settings and states of health, allowing for the use of RCV both to aid in the diagnosis of myocardial injury and for prognosis. BV-based APS appear too strict for some currently available technologies.
Abstract Objectives Reference intervals of total cholesterol concentrations in plasma and of their fractions low-density lipoprotein (LDL)-, high-density lipoprotein (HDL)-and non-HDL concentrations ...are seldom studied with respect to the relevance of age and sex. Therefore, the effect of age and sex on the reference intervals was reinvestigated with 2 indirect procedures. Methods As an indirect approach, the truncated minimum chi-square method was applied. All analyses were performed by computer programs available. The script published on the homepage of the German Society of Clinical Chemistry and Laboratory Medicine (DGKL) allows to derive a continuous age dependency of reference intervals together with their confidence and equivalence limits. The results of this approach were compared with those obtained by an indirect method developed more recently, the refineR algorithm. Results In the present study, the upper reference limits of total cholesterol varied from 5.1 to 7.8 mmol/L (197–302 mg/dL) depending on various biological variables (as age, sex, inpatients versus outpatients). These upper limits increased with age. Differences between sexes can be neglected except for the age above 80 years. The pattern of reference limits of LDL cholesterol and non-HDL cholesterol paralleled those of total cholesterol. The reference limits of HDL cholesterol were higher in women than in men but were independent of age. Conclusions Reference limits for the concentrations of total cholesterol and their fractions LDL-, HDL-and non-HDL concentrations should be stratified for age and sex.
Abstract
Laboratory measurement values require interpretative assistance e.g. so-called guide limits (GL), as an interpretative aid. Legal and normative requirements for medical laboratories do not ...provide specific information for their implementation and verification. A German Society for Clinical Chemistry and Laboratory Medicine (DGKL) Working Group GL (WG-GL) has, therefore, developed recommendations to support medical laboratories in the management of GL. A specific objective was to create a framework that mainly takes into account those aspects that can be realistically implemented by routine laboratories and that should improve the management of GL of frequently requested quantitative measurement procedures in clinical chemistry. Thus, the focus of these recommendations is on the distinction between reference interval limits and clinical decision limits as well as the determination and verification of reference interval limits. Indirect approaches are highlighted, as they enable routine laboratories with a broad analytical spectrum but limited resources to evaluate or to establish reference limits.
Abstract Objectives Indirect methods for the estimation of Reference Limits (RLs) use large data pools stored in modern laboratory information’s systems. To avoid correlation between observations ...repeated results from each patient should be excluded. Some data pools obtained are anonymized, and thereafter the data cannot be re-identified. The effect of the procedure of data selection on the estimations is not investigated yet. Methods We considered four parameters. Data sets were enclosed from two sources: a university hospital and a laboratory primarily reflecting a patient population from medical practitioners. Four algorithms were used for data selection, which generate first, last, all and non-repeated values. RLs were estimated through these data sets and compared. Results This study showed the broader reference range estimated by indirect methods if using the whole data set compared to first/last values or non-repeated values. Conclusions The use of all data without a filtering step results in a significant bias whereas the choice of first or last values has nearly no impact. The exclusion of repeated measurements results in narrower RLs. This influence confine the use of anonymous data sets where filtering is impossible for the estimation of RLs by indirect methods.
Abstract It has been observed that the estimation of reference intervals of leukocytes in whole venous blood leads to higher upper reference limits (uRLs) with indirect methods than has been reported ...in the literature determined by direct approaches. This phenomenon was reinvestigated with a newer, more advanced indirect method, and could be confirmed. Furthermore, a diurnal variation was observed with lower values during the morning and higher values in the late afternoon and at night. This observation can explain why indirect approaches using samples collected during 24 h lead to higher uRLs than direct methods applied on samples collected presumably in the morning.
Abstract Objectives Plasma glucose concentrations exhibit a pronounced daytime-dependent variation. The oscillations responsible for this are currently not considered in the determination of ...reference limits (RL) and decision limits. Methods We characterized the daily variation inherent in large-scale laboratory data from two different university hospitals (site 1 n=513,682, site 2 n=204,001). Continuous and distinct RL for daytime and night were estimated. Diurnal characteristics of glucose concentrations were further investigated by quantile regression analyses introducing age and cosinor-functions as predictors in the model. Results Diurnal variations expressed as amplitude/Midline Estimating Statistic of Rhythm (MESOR) ratio, averaged 7.7% (range 5.9–9.3%). The amplitude of glucose levels decreased with increasing concentrations. Between 06:00 and 10:00 h an average decrease of 4% has to be considered. Nocturnal glucose samples accounted for only 5% of the total amount but contributed to 19.5% of all findings over 11.1 mmol/L. Partitioning of RL between day and night is merely justified for the upper reference limit. The nocturnal upper RLs for both genders differed from those obtained during the day by 11.0 and 10.6% at site 1 and by 7.6 and 7.5% at site 2. Conclusions We conclude that indirect approaches to estimate upper RL of random plasma glucose concentrations require stratification concerning the time of sample collection.
The glucose concentration in plasma or serum is one of the most often requested analytical values in laboratory medicine. Whereas the analytical part of the glucose determination is well ...standardised, the standardisation of the pre-examination part (pre-analytical phase) is not sufficiently solved, yet. In view of the present controversial discussion regarding the most efficient prevention of pre-analytical glycolysis, the question arises whether the economical and logistic expenses for inhibiting glycolysis determining random glucose concentration are justified. In hospitals with adequate logistics (e.g. pneumatic tube systems for blood tubes) to guarantee a blood sample transport time of about 1 – 2 h, plasma or serum without prevention of glycolysis can be applied for random glucose concentrations if the reference limits are estimated by the laboratory. If such logistics are not available, especially in primary care services, either plasma or serum samples or whole blood in special tubes with anti-glycolytic additives may be sent to the laboratory.
Assessment of SARS-CoV-2 rapid antigen tests Özcürümez, Mustafa; Katsounas, Antonios; Holdenrieder, Stefan ...
Journal of laboratory medicine,
06/2021, Volume:
45, Issue:
3
Journal Article
Peer reviewed
Open access
Abstract Objectives Point-of-care antigen tests (PoC-AgTs) for the rapid detection of SARS-CoV-2 infection enable screening of additional populations with less effort, independent of laboratories and ...at a low cost. PoC-AgTs have therefore been included in national testing strategies with additional quality requirements to address limitations in specificity and sensitivity. Information given in the package inserts of the test providers should enable the user to evaluate the performance of a PoC-AgT in advance. The quality of this information has been independently assessed since the Corona Test Ordinance came into force in Germany in October 2020. Methods The completeness of analytical and diagnostic performance specifications was assessed for all package inserts publicly available via the Paul Ehrlich Institute (PEI). It was ascertained whether the minimum criteria, recommendations, and extended criteria of the PEI were comprehensibly fulfilled. The number of tests removed from the list by March 2021 was determined. Results By the closing date of the survey (17.11.2020), the PEI had listed 165 PoC-AgTs that formally fulfilled the minimum criteria and were thus reimbursed. A total of 78 identical systems were identified. Almost all providers were found to have gaps in the information on the validation results of their tests, meaning that an evaluation of performance is only possible to a limited extent. Until March 2021, 25 non-identical PoC-AgTs have been removed from the list. Conclusions Many PoC-AgTs could not be comprehensively evaluated based on the information provided by the provider. Users are therefore dependent on provider-independent sources of information.
Background and Aims: Radioembolization (RE) has recently demonstrated a non-inferior survival outcome compared to systemic therapy for advanced hepatocellular carcinoma (HCC). Therefore, current ...guidelines recommend RE for patients with advanced HCC and preserved liver function who are unsuitable for transarterial chemoembolization (TACE) or systemic therapy. However, despite the excellent safety profile of RE, post-therapeutic hepatic decompensation remains a serious complication that is difficult to predicted by standard laboratory liver function parameters or imaging modalities. LiMAx® is a non-invasive test for liver function assessment, measuring the maximum metabolic capacity for 13C-Methacetin by the liver-specific enzyme CYP 450 1A2. Our study investigates the potential of LiMAx® for predicting post-interventional decompensation of liver function. Patients and methods: In total, 50 patients with HCC with or without liver cirrhosis and not amenable to TACE or systemic treatments were included in the study. For patients prospectively enrolled in our study, LiMAx® was carried out one day before RE (baseline) and 28 and 90 days after RE. Established liver function parameters were assessed at baseline, day 28, and day 90 after RE. The relationship between baseline LiMAx® and pre-and post-interventional liver function parameters, as well as the ability of LiMAx® to predict hepatic decompensation, were analyzed. Results: We observed a strong association between baseline LiMAx® and bilirubin, albumin, ALBI grade, and MELD score. Patients presenting with Child–Pugh score B 28 days after RE or with a deterioration in Child–Pugh score by at least one point had a significantly lower baseline LiMAx® compared to those with Child–Pugh score A or with stable Child–Pugh score. The ability of LiMAx® to predict hepatic decompensation after RE was determined using ROC curve analysis and was compared to MELD score and ALBI grade. LiMAx® achieved a substantial AUC of 0.8117, comparable to MELD score and ALBI grade. Conclusion: Patients with lower LiMAx® values at baseline have a significantly increased risk for hepatic decompensation after RE, despite being categorized as Child–Pugh A. Therefore, LiMAx® can be used as an additional tool to identify patients at high risk of post-interventional hepatic failure.
Objectives Assessment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection prevalence and immunity is cornerstones in the fight against COVID-19 pandemic. For pandemic control, ...reliable assays for the detection of anti-SARS-CoV-2 antibodies are required. This pilot external quality assessment (EQA) scheme aimed to independently assess the participants' clinical performance of anti-SARS-CoV-2 testing, to identify shortcomings in clinical practice and to evaluate the suitability of the scheme format. Methods The EQA scheme consisted of eight serum samples with variable reactivity against SARS-CoV-2 intended for the analysis of anti-SARS-CoV-2 immunoglobulin (Ig)G, IgA, and IgM antibodies. Laboratories reported: (1) results for each sample and the respective method, (2) raw data from replicate testing of each sample. Results The 16 selected pilot EQA participants reported 294 interpreted results and 796 raw data results from replicate testing. The overall error rate for the anti-SARS-CoV-2 IgG, IgA, and IgM tests was 2.7, 6.9, and 16.7%, respectively. While the overall diagnostic specificity was rated as very high, sensitivity rates between 67 and 98% indicate considerable quality differences between the manufacturers, especially for IgA and IgM. Conclusions Even the results reported by the small number of participants indicate a very heterogeneous landscape of anti-SARS-CoV-2 serological testing. Differences of available tests and the individual performance of laboratories result in a success rate of 57.1% with one laboratory succeeding for all three antibody-classes. These results are an incentive for laboratories to participate in upcoming open EQA schemes that are needed to achieve a harmonization of test results and to improve serological testing.
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