scholarly journals European Biological Variation Study (EuBIVAS): within- and between-subject biological variation estimates for serum thyroid biomarkers based on weekly samplings from 91 healthy participants

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Michela Bottani ◽  
Aasne K. Aarsand ◽  
Giuseppe Banfi ◽  
Massimo Locatelli ◽  
Abdurrahman Coşkun ◽  
...  
Keyword(s):  
Large Scale ◽  
Thyroid Stimulating Hormone ◽  
Biological Variation ◽  
Healthy Individuals ◽  
Serum Samples ◽  
Free Triiodothyronine ◽  
Performance Specifications ◽  
Study Population ◽  
Variance Homogeneity ◽  
Healthy Participants

Abstract Objectives Thyroid biomarkers are fundamental for the diagnosis of thyroid disorders and for the monitoring and treatment of patients with these diseases. The knowledge of biological variation (BV) is important to define analytical performance specifications (APS) and reference change values (RCV). The aim of this study was to deliver BV estimates for thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroglobulin (TG), and calcitonin (CT). Methods Analyses were performed on serum samples obtained from the European Biological Variation Study population (91 healthy individuals from six European laboratories; 21–69 years) on the Roche Cobas e801 at the San Raffaele Hospital (Milan, Italy). All samples from each individual were evaluated in duplicate within a single run. The BV estimates with 95% CIs were obtained by CV-ANOVA, after analysis of variance homogeneity and outliers. Results The within-subject (CV I ) BV estimates were for TSH 17.7%, FT3 5.0%, FT4 4.8%, TG 10.3, and CT 13.0%, all significantly lower than those reported in the literature. No significant differences were observed for BV estimates between men and women. Conclusions The availability of updated, in the case of CT not previously published, BV estimates for thyroid markers based on the large scale EuBIVAS study allows for refined APS and associated RCV applicable in the diagnosis and management of thyroid and related diseases.

scholarly journals European Biological Variation Study (EuBIVAS): Within- and Between-Subject Biological Variation Data for 15 Frequently Measured Proteins

2019 ◽  
Vol 65 (8) ◽  
pp. 1031-1041 ◽  
Author(s):  
Anna Carobene ◽  
Aasne K Aarsand ◽  
Elena Guerra ◽  
William A Bartlett ◽  
Abdurrahman Coşkun ◽  
...  
Keyword(s):  
Acute Phase Proteins ◽  
Biological Variation ◽  
Complement Component ◽  
Serum Samples ◽  
Reactive Protein ◽  
Performance Specifications ◽  
Corrected Data ◽  
Specific Proteins ◽  
Variance Homogeneity ◽  
Complement Component 4

Abstract BACKGROUND The European Biological Variation Study (EuBIVAS) was established to deliver rigorously determined data for biological variation (BV). Here, EuBIVAS-based BV estimates are provided for α1-acid glycoprotein, α1-antitrypsin, albumin, β2-microglobulin, ceruloplasmin, complement component 3, complement component 4, C-reactive protein (CRP), cystatin C, haptoglobin, IgA, IgG, IgM, soluble transferrin receptor (sTfR), and transferrin (Trf), together with their associated analytical performance specifications (APSs) and reference change values (RCVs). METHOD Serum samples from weekly blood samplings of 91 healthy study participants (38 males and 53 females, ages 21–69 years old) over 10 consecutive weeks in 6 European laboratories were stored at −80 °C before duplicate analysis on a Roche Cobas c702. Outlier and variance homogeneity analyses were performed followed by CV-ANOVA on trend-corrected data if relevant, to determine BV and analytical variation estimates with CI and the associated RCV. RESULTS For the acute phase proteins, several participants experienced mild inflammatory episodes during the study, requiring exclusion of 7% of the 25290 results. Within-subject BV (CVI) estimates for specific proteins obtained in our study were lower than those available in the online 2014 BV database, except for Trf, whereas between-subject BV (CVG) estimates were similar. CVI and CVG estimates for sTfR, which have not previously been published, were 6.0% and 19.1%, respectively. CONCLUSIONS In addition to new BV estimates for sTfR, this EuBIVAS substudy generated more demanding APS for frequently requested plasma specific proteins. APS for CRP should not be calculated from BV data except when CRP is used as a risk factor for cardiovascular disease.

scholarly journals Within-subject and between-subject biological variation estimates of 21 hematological parameters in 30 healthy subjects

2018 ◽  
Vol 56 (8) ◽  
pp. 1309-1318 ◽  
Author(s):  
Abdurrahman Coşkun ◽  
Anna Carobene ◽  
Meltem Kilercik ◽  
Mustafa Serteser ◽  
Sverre Sandberg ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Complete Blood Count ◽  
Hematological Parameters ◽  
Hemoglobin Concentration ◽  
Biological Variation ◽  
Mean Corpuscular Hemoglobin ◽  
Mean Values ◽  
Performance Specifications ◽  
The Mean ◽  
Variance Homogeneity

Abstract Background: The complete blood count (CBC) is used to evaluate health status in the contexts of various clinical situations such as anemia, infection, inflammation, trauma, malignancies, etc. To ensure safe clinical application of the CBC, reliable biological variation (BV) data are required. The study aim was to define the BVs of CBC parameters employing a strict protocol. Methods: Blood samples, drawn from 30 healthy subjects (17 females, 13 males) once weekly for 10 weeks, were analyzed using a Sysmex XN 3000 instrument. The data were assessed for normality, trends, outliers and variance homogeneity prior to coefficient of variation (CV)-analysis of variance (ANOVA). Sex-stratified within-subject (CVI) and between-subjects (CVG) BV estimates were determined for 21 CBC parameters. Results: For leukocyte parameters, with the exception of lymphocytes and basophils, significant differences were found between female/male CVI estimates. The mean values of all erythrocyte-, reticulocyte- and platelet parameters differed significantly between the sexes, except for mean corpuscular hemoglobin concentration, mean corpuscular volume and platelet numbers. Most CVI and CVG estimates appear to be lower than those previously published. Conclusions: Our study, based on a rigorous protocol, provides updated and more stringent BV estimates for CBC parameters. Sex stratification of data is necessary when exploring the significance of changes in consecutive results and when setting analytical performance specifications.

scholarly journals The EuBIVAS Project: Within- and Between-Subject Biological Variation Data for Serum Creatinine Using Enzymatic and Alkaline Picrate Methods and Implications for Monitoring

2017 ◽  
Vol 63 (9) ◽  
pp. 1527-1536 ◽  
Author(s):  
Anna Carobene ◽  
Irene Marino ◽  
Abdurrahman Coşkun ◽  
Mustafa Serteser ◽  
Ibrahim Unsal ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Clinical Chemistry ◽  
Biological Variation ◽  
European Federation ◽  
Healthy Individuals ◽  
Homogeneity Analysis ◽  
Variation Data ◽  
Performance Specifications ◽  
Age Range ◽  
Analytical Variation

Abstract BACKGROUND The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) European Biological Variation Study (EuBIVAS) has been established to deliver rigorously determined biological variation (BV) indices. EuBIVAS determined BV for serum creatinine using the enzymatic and alkaline picrate measurement methods. METHOD In total, 91 healthy individuals (38 males, 53 females; age range, 21–69 years) were bled for 10 consecutive weeks at 6 European laboratories. An equivalent protocol was followed at each center. Sera were stored at −80 °C before analysis. Analyses for each patient were performed in duplicate within a single run on an ADVIA 2400 system (San Raffaele Hospital, Milan). The data were subjected to outlier and homogeneity analysis before performing CV-ANOVA to determine BV and analytical variation (CVA) estimates with confidence intervals (CI). RESULTS The within-subject BV estimates [CVI (95% CI)] were similar for enzymatic [4.4% (4.2–4.7)] and alkaline picrate [4.7% (4.4–4.9)] methods and lower than the estimate presently available online (CVI = 5.9%). No significant male/female BV differences were found. Significant differences were observed in mean creatinine values between men and women and between Turkish individuals and those of other nationalities. Between-subject BV (CVG) estimates, stratified accordingly, produced CVG values similar to historical BV data. CVA was 1.1% for the enzymatic and 4.4% for alkaline picrate methods, indicating that alkaline picrate methods fail to fulfill analytical performance specifications for imprecision (CVAPS). CONCLUSIONS The serum creatinine CVI obtained by EuBIVAS specifies a more stringent CVAPS than previously identified. The alkaline picrate method failed to meet this CVAPS, raising questions regarding its future use.

scholarly journals Effects of a Single Venous Dose of Zinc on Thyroid Status in Healthy Individuals and Patients With Graves' Disease

2000 ◽  
Vol 7 (3) ◽  
pp. 151-155 ◽  
Author(s):  
Lubna Farooqi ◽  
Gláucia M. F. S. Mazeto ◽  
Tadao Shuhama ◽  
José Brandão-Neto
Keyword(s):  
Thyroid Function ◽  
Plasma Levels ◽  
Thyroid Stimulating Hormone ◽  
Graves Disease ◽  
Zinc Metabolism ◽  
Healthy Individuals ◽  
Free Triiodothyronine ◽  
Hormone Synthesis ◽  
Hyperthyroid Patients ◽  
Tsh Levels

Zinc metabolism may regulate thyroid function acting at TRH (thyrotropin-releasing hormone) synthesis, peripheral deiodination of T4 (tetraiodothyronine), and binding of thyroid hormones to nuclear receptors. The aim of this study was to investigate the effect of acute zinc administration on TSH (thyroid-stimulating hormone), FT3 (free triiodothyronine), and FT4 (free tetraiodothyronine) in 10 healthy individuals and 12 hyperthyroid patients with Graves' disease. All these individuals were studied following 25 mg Zn++ administered intravenously, at 7:00 a.m. after 12 h fast. Blood samples collected at 0, 3, 30, 60, 90, and 120 min after zinc administration showed no significant alteration in the plasma levels of TSH, FT3, and FT4 in hyperthyroid patients. There were no changes in the plasma levels of FT3 and FT4 in the control subjects, but TSH levels were acutely depressed by zinc administration. This study suggests that zinc given acutely and in pharmacological doses does not affect thyroid function in hyperthyroid subjects, but affect plasma TSH levels in healthy individuals.

scholarly journals METHODOLOGICAL ISSUES OF DETERMINING CONCENTRATIONS OF SOME CYTOKINES IN PERIPHERAL MBLOOD FROM HEALTHY INDIVIDUALS

2018 ◽  
Vol 20 (5) ◽  
pp. 763-774
Author(s):  
N. A. Arsentieva ◽  
Areg A. Totolian
Keyword(s):  
Blood Serum ◽  
Large Scale ◽  
Human Peripheral Blood ◽  
Biological Fluids ◽  
Control Group ◽  
Healthy Individuals ◽  
Serum Samples ◽  
Normal Ranges ◽  
Number Of Patients ◽  
Cytokine Levels

Cytokines are the most important factors in pathogenesis of infectious, allergic, autoimmune, lymphoproliferative diseases and immunopathological processes. Many cytokines are very useful therapeutic targets for immunodiagnostics of different human diseases. Measurement of the cytokine levels by immunochemical methods in various biological fluids is usually used for diagnostic evaluation. Content analysis of research articles from two Russian immunological journals, “Meditsinskaya Immunologiya” = “Medical Immunology (Russia)” and “Infektsiya i immunitet” = “Russian Journal of Infection and Immunity,”, shows that ELISA, xMAP multiplex immunoassay, and CBA technologies are the most common methods used in clinical and immunological studies aimed for determination of cytokine contents in blood serum/plasma. Normal ranges of some plasma/serum cytokines in healthy individuals were subject to wide variations when using different methods and specific reagents from various manufacturers. The normal ranges applied by the CBA-technology, are significantly higher than appropriate values obtained by ELISA or xMAP-technologies. Most studies included a small control group, usually limited by 15-20 persons. In most of these works, blood serum samples were used for assays, whereas EDTA-conserved plasma was taken only in few studies. It has been concluded that the results of cytokine measurements in blood serum/plasma in healthy individuals vary in wide ranges, and depend on many factors, e.g., initial sampling material, mode of technology, type of test systems, and characteristics of the group under study: number of patients, age, gender, geographical factor, etc. The mentioned data demonstrate a need for large-scale multicenter clinical studies, in order to standardize measurements of the cytokine levels in human peripheral blood and to specify their normal values.

scholarly journals First Estimation of Reference Intervals for Thyroid-Stimulating Hormone and Thyroid Hormones in Slovenian Population

2021 ◽  
Vol 68 (2) ◽  
pp. 488-493
Author(s):  
Adrijana Oblak ◽  
Ajda Biček ◽  
Edvard Pirnat ◽  
Katja Zaletel ◽  
Simona Gaberšček
Keyword(s):  
Thyroid Hormones ◽  
Thyroid Disease ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Reference Intervals ◽  
Thyroid Stimulating Hormone ◽  
Healthy Individuals ◽  
Free Triiodothyronine ◽  
Percentile Method ◽  
Stimulating Hormone

For thyroid function estimation and clinical decision making, use of appropriate reference intervals for thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) is crucial. For each laboratory, establishment of own reference intervals is advised. For the first Slovenian estimation of reference intervals for thyroid hormones a large group of 1722 healthy individuals without thyroid disease was established retrospectively. Hormone analyses were performed on automated analyser Advia Centaur XP Immunoassay System (Siemens Healthineers), which reference intervals for TSH, fT4 and fT3 were 0.55–4.78 mIU/L, 11.5–22.7 pmol/L, and 3.5–6.5 pmol/L, respectively. Statistical analysis followed non-parametric percentile method. Our laboratory reference intervals for TSH, fT4 and fT3 are mostly narrower than intervals given by manufacturer. Median value, lower and upper limit for TSH, fT4 and fT3 were 1.98 (0.59–4.23) mIU/L, 14.5 (11.3–18.8) pmol/L and 4.82 (3.79–6.05) pmol/L, respectively. Most likely, an inclusion of a high number of healthy individuals without thyroid disease was a reason for such results.

scholarly journals Biological Variation of Cardiac Troponins in Health and Disease: A Systematic Review and Meta-analysis

2020 ◽  
Author(s):  
Jorge Diaz-Garzon ◽  
Pilar Fernandez-Calle ◽  
Sverre Sandberg ◽  
Mustafa Özcürümez ◽  
William A Bartlett ◽  
...  
Keyword(s):  
Troponin I ◽  
Limit Of Detection ◽  
Troponin T ◽  
Meta Analysis ◽  
High Sensitivity ◽  
Sampling Interval ◽  
Biological Variation ◽  
Healthy Individuals ◽  
Performance Specifications ◽  
Meta Analyses

Abstract Background 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. Methods 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. Results 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. Conclusions 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.

scholarly journals Second-Trimester Reference Intervals for Thyroid Tests: The Role of Ethnicity

2007 ◽  
Vol 53 (9) ◽  
pp. 1658-1664 ◽  
Author(s):  
Sonia L La’ulu ◽  
William L Roberts
Keyword(s):  
Thyroid Function ◽  
Thyroid Function Test ◽  
Reference Interval ◽  
Reference Intervals ◽  
Thyroid Stimulating Hormone ◽  
Adverse Outcomes ◽  
Thyroid Peroxidase ◽  
Serum Samples ◽  
Free Triiodothyronine ◽  
Thyroglobulin Autoantibodies

Abstract Background: Thyroid function changes during pregnancy, complicating the diagnosis of thyroid disorders. Maternal thyroid dysfunction has been associated with a variety of adverse outcomes. We evaluated thyroid function test results by ethnicity and week of gestation during the 2nd trimester of pregnancy. Methods: We collected 3064 blood specimens in serum tubes from Asians (13%), blacks (22%), Hispanics (23%), and whites (42%). We measured thyroid-stimulating hormone (TSH), total and free thyroxine (TT4 and FT4), total and free triiodothyronine (TT3 and FT3), thyroglobulin autoantibodies (TgAb), and thyroid peroxidase autoantibodies (TPOAb) by use of an ARCHITECT i2000SR (Abbott Diagnostics). The TSH reference interval was calculated for samples negative for both TgAb and TPOAb and reference intervals for TT4, FT4, TT3, and FT3 in antibody-negative samples with normal TSH. Results: Serum samples were positive for TgAb in 10.6%, 1.8%, 6.2%, 6.5%, and 5.9% of Asian, black, Hispanic, white, and combined groups, respectively. Samples were positive for TPOAb in 12.4%, 4.1%, 11.8%, 12.3%, and 10.4% of the same groups, respectively. The nonparametric reference intervals for all participants were 0.15–3.11 mIU/L (TSH), 9.3–15.2 pmol/L (0.72–1.18 ng/dL; FT4), 89.0–176.3 nmol/L (6.90–13.67 μg/dL; TT4), 3.82–5.96 pmol/L (2.48–3.87 pg/mL; FT3), and 1.82–3.68 nmol/L (118–239 ng/dL; TT3). Conclusions: Blacks had lower prevalences of TgAb and TPOAb positivity and of increased serum TSH. The prevalence of TgAb and TPOAb positivity was highest in Asians. Whites had the highest prevalence of increased TSH. The lower and upper reference limits of TT3 were significantly lower for Asians. Reference intervals for women in the 2nd trimester were different from those of nonpregnant individuals.

Benefits and harms of wellness initiatives

2019 ◽  
Vol 57 (10) ◽  
pp. 1494-1500 ◽  
Author(s):  
Clare Fiala ◽  
Jennifer Taher ◽  
Eleftherios P. Diamandis
Keyword(s):  
Health Care ◽  
Systems Biology ◽  
Large Scale ◽  
Whole Genome ◽  
Healthy Individuals ◽  
Therapeutic Measures ◽  
Limited Health ◽  
Wellness Initiatives ◽  
Healthy Participants ◽  
Selection Of

Abstract Wellness projects are large scale studies of healthy individuals through extensive laboratory and other testing. The “Hundred Person Wellness Study”, was one of the first to report results and lessons from its approach and these lessons can be applied to other wellness projects which are being undertaken by major companies and other organizations. In the “Hundred Person Wellness Study”, investigators from the Institute for Systems Biology (ISB) sequenced the genome, and analyzed the blood, saliva, urine and microbiome of 108 healthy participants every 3 months, for 9 months, to look for subtle changes signifying the transition to disease. We discuss some of the possible shortcomings of this approach; questioning the need to “improve” biomarker levels, excessive testing leading to over-diagnosis and over-treatment, expected results and improvements, selection of tests, problems with whole genome sequencing and speculations on therapeutic measures. We hope this discussion will lead to a continued evaluation of wellness interventions, leading to strategies that truly benefit patients within the constraint of limited health care resources.

scholarly journals Within- and between-subject biological variation data for serum zinc, copper and selenium obtained from 68 apparently healthy Turkish subjects

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Abdurrahman Coşkun ◽  
Anna Carobene ◽  
Aasne K. Aarsand ◽  
Fehime B. Aksungar ◽  
Mustafa Serteser ◽  
...  
Keyword(s):  
Inductively Coupled Plasma ◽  
Serum Zinc ◽  
Population Based ◽  
Biological Variation ◽  
Serum Samples ◽  
Inductively Coupled ◽  
Essential Components ◽  
Serum Zn ◽  
Males And Females ◽  
Variance Homogeneity

Abstract Objectives Trace elements (TrEL) are nutritionally essential components in maintaining health and preventing diseases. There is a lack of reliable biological variation (BV) data for TrELs, required for the diagnosis and monitoring of TrEL disturbances. In this study, we aimed to provide updated within- and between-subject BV estimates for zinc (Zn), copper (Cu) and selenium (Se). Methods Weekly serum samples were drawn from 68 healthy subjects (36 females and 32 males) for 10 weeks and stored at −80 °C prior to analysis. Serum Zn, Cu and Se levels were measured using inductively-coupled plasma mass spectrometry (ICP-MS). Outlier and variance homogeneity analyses were performed followed by CV-ANOVA (Røraas method) to determine BV and analytical variation estimates with 95% CI and the associated reference change values (RCV) for all subjects, males and females. Results Significant differences in mean concentrations between males and females were observed, with absolute and relative (%) differences for Zn at 0.5 μmol/L (3.5%), Cu 2.0 μmol/L (14.1%) and Se 0.06 μmol/L (6.0%). The within-subject BV (CVI [95% CI]) estimates were 8.8% (8.2–9.3), 7.8% (7.3–8.3) and 7.7% (7.2–8.2) for Zn, Cu and Se, respectively. Within-subject biological variation (CVI) estimates derived for male and female subgroups were similar for all three TrELs. Marked individuality was observed for Cu and Se. Conclusions The data of this study provides updated BV estimates for serum Zn, Cu and Se derived from a stringent protocol and state of the art methodologies. Furthermore, Cu and Se display marked individuality, highlighting that population based reference limits should not be used in the monitoring of patients.

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