First data on the biological variation and quality specifications for plasma ammonia concentrations in healthy subjects

2016 ◽  
Vol 54 (5) ◽  
Author(s):  
Fatma Ucar ◽  
Gonul Erden ◽  
Seyda Ozdemir ◽  
Nurgul Ozcan ◽  
Erdem Bulut ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Plasma Sample ◽  
Biological Variation ◽  
Test Results ◽  
Healthy Individuals ◽  
Variation Data ◽  
Quality Specifications ◽  
Collection Period ◽  
First Time ◽  
Analytical Variation

AbstractBackground:Most of the factors causing preanalytical and analytical variation in ammonia measurement have been identified. Biological variation data for ammonia is still lacking. We therefore estimated the components of biological variation (within-subject=CVMethods:Blood samples from 20 healthy subjects were collected in K2EDTA tubes daily over a period of 4 consecutive days from each subject. Each plasma sample was split into two aliquots; one was immediately analyzed as the samples were collected and the other was stored –80 °C until testing at the end of the collection period and analyzed at once in one analytical run. All samples were analyzed in duplicate. Estimations were calculated according to Fraser and Harris methods.Results:CVConclusions:The present study for the first time described the components of biological variation for ammonia in healthy individuals. These data regarding biological variation of ammonia could be useful for a better evaluation of ammonia test results in clinical interpretation and for determining quality specifications based on biological variation.

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 Critical appraisal and meta-analysis of biological variation studies on glycosylated albumin, glucose and HbA1c

2020 ◽  
Vol 1 (3) ◽  
Author(s):  
Carmen Ricós ◽  
Pilar Fernández-Calle ◽  
Elisabet Gonzalez-Lao ◽  
Margarida Simón ◽  
Jorge Díaz-Garzón ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Critical Appraisal ◽  
Meta Analysis ◽  
Biological Variation ◽  
Evidence Based ◽  
Literature Searches ◽  
Variation Data ◽  
Global Estimates ◽  
Systematic Literature Searches

AbstractObjectivesNumerous biological variation (BV) studies have been performed over the years, but the quality of these studies vary. The objectives of this study were to perform a systematic review and critical appraisal of BV studies on glycosylated albumin and to deliver updated BV estimates for glucose and HbA1c, including recently published high-quality studies such as the European Biological Variation study (EuBIVAS).MethodsSystematic literature searches were performed to identify BV studies. Nine publications not included in a previous review were identified; four for glycosylated albumin, three for glucose, and three for HbA1c. Relevant studies were appraised by the Biological Variation Data Critical Appraisal Checklist (BIVAC). Global BV estimates were derived by meta-analysis of BIVAC-compliant studies in healthy subjects with similar study design.ResultsOne study received BIVAC grade A, 2B, and 6C. In most cases, the C-grade was associated with deficiencies in statistical analysis. BV estimates for glycosylated albumin were: CVI=1.4% (1.2–2.1) and CVG=5.7% (4.7–10.6), whereas estimates for HbA1c, CVI=1.2% (0.3–2.5), CVG=5.4% (3.3–7.3), and glucose, CVI=5.0% (4.1–12.0), CVG=8.1% (2.7–10.8) did not differ from previously published global estimates.ConclusionsThe critical appraisal and rating of BV studies according to their methodological quality, followed by a meta-analysis, generate robust, and reliable BV estimates. This study delivers updated and evidence-based BV estimates for glycosylated albumin, glucose and HbA1c.

Methylphenidate reduces orienting bias in healthy individuals

2021 ◽  
pp. 026988112199688
Author(s):  
Leehe Peled-Avron ◽  
Hagar Gelbard Goren ◽  
Noa Brande-Eilat ◽  
Shirel Dorman-Ilan ◽  
Aviv Segev ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Asymmetric Effect ◽  
Healthy Individuals ◽  
Double Blind ◽  
Spatial Orienting ◽  
Individual Trait ◽  
Neurological Patients ◽  
Dopamine Signaling ◽  
First Time ◽  
Neural Effect

Background: Healthy individuals show subtle orienting bias, a phenomenon known as pseudoneglect, reflected in a tendency to direct greater attention toward one hemispace. Accumulating evidence indicates that this bias is an individual trait, and attention is preferentially directed contralaterally to the hemisphere with higher dopamine signaling. Administration of methylphenidate (MPH), a dopamine transporter inhibitor, was shown to normalize aberrant spatial attention bias in psychiatric and neurological patients, suggesting that the reduced orienting bias following administration of MPH reflects an asymmetric effect of the drug, increasing extracellular dopamine in the hemisphere with lower dopamine signaling. Aim: We predicted that, similarly to its effect on patients with brain pathology, MPH will reduce the orienting bias in healthy subjects. Methods: To test this hypothesis, we examined the behavioral effects of a single dose (20 mg) of MPH on orienting bias in 36 healthy subjects (18 females) in a randomized, double-blind placebo-controlled, within-subject design, using the greyscales task, which has been shown to detect subtle attentional biases in both patients and healthy individuals. Results/outcomes: Results demonstrate that healthy individuals vary in both direction and magnitude of spatial orienting bias and show reduced magnitude of orienting bias following MPH administration, regardless of the initial direction of asymmetry. Conclusions/interpretations: Our findings reveal, for the first time in healthy subjects, that MPH decreases spatial orienting bias in an asymmetric manner. Given the well-documented association between orienting bias and asymmetric dopamine signaling, these findings also suggest that MPH might exert a possible asymmetric neural effect in the healthy brain.

Factors contributing to intra-individual variation of serum constituents: Physiological day-to-day variation in concentrations of 10 specific proteins in sera of healthy subjects.

1976 ◽  
Vol 22 (10) ◽  
pp. 1635-1638 ◽  
Author(s):  
B E Statland ◽  
P Winkel ◽  
L M Killingsworth
Keyword(s):  
Data Analysis ◽  
Individual Variation ◽  
Healthy Subjects ◽  
Interindividual Variation ◽  
Complement C3 ◽  
Variation Data ◽  
Human Sera ◽  
Specific Proteins ◽  
Alpha1 Antitrypsin ◽  
Analytical Variation

Abstract Using an automated immunoprecipitin method, we assayed human sera for 10 proteins: haptoglobin, orosomucoid, transferrin, alpha1 antitrypsin, alpha2-macroglobulin, IgG, IGa, IgM, complement C3, and complement C4. Blood from 14 healthy subjects (25-40y) was sampled on six separate days. From each venipuncture serum was divided into four eliquots; two were assayed on the day of venipuncture and two were frozen and kept until the end of the study, when all of the frozen samples were analyzed in one batch. With this experimental design, batch-to-batch analytical variation could be estimated, and we avoided confounding it with the biological variation. Data analysis was based on the analysis of variance technique. The average physiological intra-individual coefficient of variation ranged from 2.5% for transferrin to 11.1% for orosomucoid. THe interindividual variation ranged from 9.5% for transferrin to 70.5% for haptoglobin and the ratio between intra-individual variation and interindividual variation ranged from 0.66 for IgM to 0.26 for orosomucoid and transferrin.

scholarly journals Within-day biological variation and hour-to-hour reference change values for hematological parameters

2017 ◽  
Vol 55 (7) ◽  
Author(s):  
Judith M. Hilderink ◽  
Lieke J.J. Klinkenberg ◽  
Kristin M. Aakre ◽  
Norbert C.J. de Wit ◽  
Yvonne M.C. Henskens ◽  
...  
Keyword(s):  
Hematological Parameters ◽  
Biological Variation ◽  
Natural Fluctuation ◽  
Sample Collection ◽  
Blood Samples ◽  
Variation Data ◽  
Random Fluctuations ◽  
Analytical Variation ◽  
Variability Data

AbstractBackground:Middle- and long-term biological variation data for hematological parameters have been reported in the literature. Within-day 24-h variability profiles for hematological parameters are currently lacking. However, comprehensive hour-to-hour variability data are critical to detect diurnal cyclical rhythms, and to take into account the ‘time of sample collection’ as a possible determinant of natural fluctuation. In this study, we assessed 24-h variation profiles for 20 hematological parameters.Methods:Blood samples were collected under standardized conditions from 24 subjects every hour for 24 h. At each measurement, 20 hematological parameters were determined in duplicate. Analytical variation (CVResults:All parameters showed higher CVConclusions:We present complete 24-h variability profiles for 20 hematological parameters. Hour-to-hour reference changes values may help to better discriminate between random fluctuations and true changes in parameters with rhythmic diurnal oscillations.

scholarly journals Biological Variation of Vitamins in Blood of Healthy Individuals

2005 ◽  
Vol 51 (11) ◽  
pp. 2145-2150 ◽  
Author(s):  
Dinesh K Talwar ◽  
Mohammed K Azharuddin ◽  
Cathy Williamson ◽  
Yee Ping Teoh ◽  
Donald C McMillan ◽  
...  
Keyword(s):  
Whole Blood ◽  
Total Error ◽  
Reference Intervals ◽  
Biological Variation ◽  
Reference Change Value ◽  
Objective Quality ◽  
Variation Data ◽  
Quality Specifications ◽  
Index Of Individuality ◽  
Apparently Healthy

Abstract Background: Components of biological variation can be used to define objective quality specifications (imprecision, bias, and total error), to assess the usefulness of reference values [index of individuality (II)], and to evaluate significance of changes in serial results from an individual [reference change value (RCV)]. However, biological variation data on vitamins in blood are limited. The aims of the present study were to determine the intra- and interindividual biological variation of vitamins A, E, B1, B2, B6, C, and K and carotenoids in plasma, whole blood, or erythrocytes from apparently healthy persons and to define quality specifications for vitamin measurements based on their biology. Methods: Fasting plasma, whole blood, and erythrocytes were collected from 14 healthy volunteers at regular weekly intervals over 22 weeks. Vitamins were measured by HPLC. From the data generated, the intra- (CVI) and interindividual (CVG) biological CVs were estimated for each vitamin. Derived quality specifications, II, and RCV were calculated from CVI and CVG. Results: CVI was 4.8%–38% and CVG was 10%–65% for the vitamins measured. The CVIs for vitamins A, E, B1, and B2 were lower (4.8%–7.6%) than for the other vitamins in blood. For all vitamins, CVG was higher than CVI, with II <1.0 (range, 0.36–0.95). The RCVs for vitamins were high (15.8%–108%). Apart from vitamins A, B1, and erythrocyte B2, the imprecision of our methods for measurement of vitamins in blood was within the desirable goal. Conclusions: For most vitamin measurements in plasma, whole blood, or erythrocytes, the desirable imprecision goals based on biological variation are obtainable by current methodologies. Population reference intervals for vitamins are of limited value in demonstrating deficiency or excess.

Biological variation of serum neurofilament light chain

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Claus Vinter Bødker Hviid ◽  
Anne Tranberg Madsen ◽  
Anne Winther-Larsen
Keyword(s):  
Light Chain ◽  
Reference Intervals ◽  
Biological Variation ◽  
Healthy Individuals ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Linear Mixed Effects ◽  
Serial Measurements ◽  
Analytical Variation ◽  
Apparently Healthy

Abstract Objectives The neurofilament light chain (NfL) has emerged as a versatile biomarker for CNS-diseases and is approaching clinical use. The observed changes in NfL levels are frequently of limited magnitude and in order to make clinical decisions based on NfL measurements, it is essential that biological variation is not confused with clinically relevant changes. The present study was designed to evaluate the biological variation of serum NfL. Methods Apparently healthy individuals (n=33) were submitted to blood draws for three days in a row. On the second day, blood draws were performed every third hour for 12 h. NfL was quantified in serum using the Simoa™ HD-1 platform. The within-subject variation (CVI) and between-subject variation (CVG) were calculated using linear mixed-effects models. Results The overall median value of NfL was 6.3 pg/mL (range 2.1–19.1). The CVI was 3.1% and the CVG was 35.6%. An increase in two serial measurements had to exceed 24.3% to be classified as significant at the 95% confidence level. Serum NfL levels remained stable during the day (p=0.40), whereas a minute variation (6.0–6.6 pg/mL) was observed from day-to-day (p=0.02). Conclusions Serum NfL is subject to tight homeostatic regulation with none or neglectable semidiurnal and day-to-day variation, but considerable between-subject variation exists. This emphasizes serum NfL as a well-suited biomarker for disease monitoring, but warrants caution when interpreting NfL levels in relation to reference intervals in a diagnosis setting. Furthermore, NfL’s tight regulation requires that the analytical variation is kept at a minimum.

scholarly journals Estimation and Application of Biological Variation of Urinary δ-Aminolevulinic Acid and Porphobilinogen in Healthy Individuals and in Patients with Acute Intermittent Porphyria

2006 ◽  
Vol 52 (4) ◽  
pp. 650-656 ◽  
Author(s):  
Aasne K Aarsand ◽  
Per Hyltoft Petersen ◽  
Sverre Sandberg
Keyword(s):  
Aminolevulinic Acid ◽  
Acute Intermittent Porphyria ◽  
Fold Increase ◽  
Biological Variation ◽  
Test Results ◽  
Healthy Individuals ◽  
Short Term ◽  
Real Change ◽  
Previous Sample

Abstract Background: Diagnosis of an attack of acute intermittent porphyria (AIP) is based on the demonstration of increased concentrations of porphobilinogen (PBG) and δ-aminolevulinic acid (ALA) in urine, but many AIP patients also have high baseline concentrations in remission. The aim of this study was to estimate the biological variations of ALA, PBG, and porphyrins in healthy individuals and AIP patients to improve interpretation of test results. Methods: Fifteen healthy individuals and 15 AIP patients were included, and biological variations were calculated based on urine samples collected weekly for 10 consecutive weeks. For the AIP patients, long-term variations were also estimated based on 7 samples collected through a 2-year period. Results: The porphyrin variances were inhomogeneously distributed; biological variations of porphyrins were therefore not calculated. The within-subject biological variations of ALA and PBG were 16%–20% in the short-term settings and for PBG, 25% in the long-term setting, giving reference change values of ∼50% and 70%, respectively. The probability of detecting a 100% real change in PBG was 97% in the short-term setting and 80% in the long-term setting. Conclusions: In an AIP patient, a 2-fold increase in PBG, independent of the baseline concentration, will be detected with a probability >80% and is most likely related to the patient’s disease and not caused only by analytical and biological variation. When PBG is used in the assessment of AIP-related symptoms, both the PBG concentration in remission and the length of time since the previous sample must be considered.

Within-subject biological variation in disease: collated data and clinical consequences

2007 ◽  
Vol 44 (4) ◽  
pp. 343-352 ◽  
Author(s):  
Carmen Ricós ◽  
Natalia Iglesias ◽  
José-Vicente García-Lario ◽  
Margarita Simón ◽  
Fernando Cava ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Quantitative Data ◽  
Clinical Applications ◽  
Biological Variation ◽  
Healthy Individuals ◽  
Set Point ◽  
Disease States ◽  
Reference Change Value ◽  
Clinical Consequences ◽  
Disease Specific

Quantitative data on the components of biological variation (BV) are used for several purposes, including calculating the reference change value (RCV) required for the assessment of the significance of changes in serial results in an individual. Pathology may modify the set point in diseased patients and, more importantly, the variation around that set-point. Our aim was to collate all published BV data in situations other than health. We report the within-subject coefficient of variation (CVI) for 66 quantities in 34 disease states. We compared the results with the CVI determined in healthy individuals and examined whether the data derived in specific diseases could be useful for clinical applications. For the majority of quantities studied, CVI values are of the same order in disease and health: thus the use of RCV derived from healthy subjects for monitoring patients would be reasonable. However, for a small number of quantities considered to be disease specific markers, the CVI differed from those in health. This could mean that RCV derived from healthy CVI may be inappropriate for monitoring patients in certain diseases. Hence, disease-specific RCVs may be clinically useful.

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