Abstract
Objectives
The estimates of biological variation (BV) have traditionally been determined using direct methods, which present limitations. In response to this issue, two papers have been ...published addressing these limitations by employing indirect methods. Here, we present a new procedure, based on indirect methods that analyses data collected within a multicenter pilot study. Using this method, we obtain CV
I
estimates and calculate confidence intervals (CI), using the EFLM-BVD CV
I
estimates as gold standard for comparison.
Methods
Data were collected over a 18-month period for 7 measurands, from 3 Spanish hospitals; inclusion criteria: patients 18–75 years with more than two determinations. For each measurand, four different strategies were carried out based on the coefficient of variation ratio (rCoeV) and based on the use of the bootstrap method (OS1, RS2 and RS3). RS2 and RS3 use symmetry reference change value (RCV) to clean database.
Results
RS2 and RS3 had the best correlation for the CV
I
estimates with respect to EFLM-BVD. RS2 used the symmetric RCV value without eliminating outliers, while RS3 combined RCV and outliers. When using the rCoeV and OS1 strategies, an overestimation of the CV
I
value was obtained.
Conclusions
Our study presents a new strategy for obtaining robust CV
I
estimates using an indirect method together with the value of symmetric RCV to select the target population. The CV
I
estimates obtained show a good correlation with those published in the EFLM-BVD database. Furthermore, our strategy can resolve some of the limitations encountered when using direct methods such as calculating confidence intervals.
ObjectivesNumerous 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.
A lo largo de los años se han publicado numerosos artículos sobre variación biológica (VB) de diferente calidad. Los objetivos de este trabajo fueron realizar una revisión sistemática y una ...evaluación crítica de los estudios de VB para albúmina glicosilada y proporcionar datos actualizados de VB para glucosa y HbA1c, incluyendo prestigiosos estudios recientemente publicados como el Estudio de Variación Biológica Europea (EuBIVAS).
Background Interpretation of the complete blood count (CBC) parameters requires reliable biological variation (BV) data. The aims of this study were to appraise the quality of publications reporting ...BV data for CBC parameters by applying the BV Data Critical Appraisal Checklist (BIVAC) and to deliver global BV estimates based on BIVAC compliant studies. Methods Relevant publications were identified by a systematic literature search and evaluated for their compliance with the 14 BIVAC criteria, scored as A, B, C or D, indicating decreasing compliance. Global CVI and CVG estimates with 95% CI were delivered by a meta-analysis approach using data from BIVAC compliant papers (grades A-C). Results In total, 32 studies were identified; four received a BIVAC grade A, 2 B, 20 C and 6 D. Meta-analysis derived CVI and CVG estimates were generally lower or in line with those published in a historical BV database available online. Except for reticulocytes, CVI estimates of erythrocyte related parameters were below 3%, whereas platelet (except MPV and PDW) and leukocyte related parameters ranged from 5% to 15%. Conclusions A systematic review of CBC parameters has provided updated, global estimates of CVI and CVG that will be included in the newly published European Federation of Clinical Chemistry and Laboratory Medicine BV Database.
Resumen
Introducción
El objetivo de este estudio es comprobar la evolución de las especificaciones de la prestación analítica (EPA) utilizadas en programas de garantía externa de la calidad (EQA) y ...el papel de un programa de categoría 1 en la vigilancia de la estandarización de la prestación de los laboratorios clínicos en España.
Métodos
Se ha revisado la bibliografía sobre tipos de especificaciones de la calidad usados en programas de otros países y se ha comprobado su evolución; se ha comparado el posible impacto de distintas EPA empleadas en ocho países en la toma de decisiones clínicas con tres ejemplos de magnitudes: sodio, tirotropina (TSH) y tiempo de tromboplastina parcial activado (TTPA).
Resultados
Se ha evidenciado la estandarización entre métodos analíticos comprobando si los resultados medios se desvían respecto al valor de referencia certificado del control dentro de las EPA derivadas de la variación biológica (VB). Las EPA usadas en EQA han evolucionado desde el estado del arte hacia la VB. Si se aplican los resultados que se aceptarían con algunas EPA se podrían producir decisiones clínicas erróneas.
Conclusiónes
En España, solo 2 de las 18 magnitudes biológicas estudiadas se pueden considerar bien estandarizadas. Sería necesaria una colaboración más estrecha entre los laboratorios y proveedores de sistemas analíticos para resolver las discrepancias.
Stability of a measurand in a specimen is a function of the property variation over time in specific storage conditions, which can be expressed as a stability equation, and is usually simplified to ...stability limits (SLs). Stability studies show differences or even inconsistent results due to the lack of standardized experimental designs and heterogeneity of the chosen specifications. Although guidelines for the validation of sample collection tubes have been published recently, the measurand stability evaluation is not addressed. This document provides an easy guideline for the development of a stability test protocol based on a two-step process. A preliminary test is proposed to evaluate the stability under laboratory habitual conditions. The loss of stability is assessed by comparing measurement values of two samples obtained from the same patient and analyzed at different time points. One of them is analyzed under optimal conditions (basal sample). The other is stored under specific stability conditions for a time set by the laboratory (test sample). Differences are expressed using percentage deviation (PD%) to facilitate comparison with specifications. When the preliminary test demonstrates instability, a comprehensive test is proposed in order to define the stability equation and to specify SLs. Several samples are collected from a set of patients. The basal sample is analyzed under optimal conditions, whereas analysis of test samples is delayed at time intervals. For each patient PD% is calculated as the difference between measurements for every test sample and its basal one and represented in a coordinate graph versus time.
Resumen
Objetivos
A lo largo de los años se han publicado numerosos artículos sobre variación biológica (VB) de diferente calidad. Los objetivos de este trabajo fueron realizar una revisión ...sistemática y una evaluación crítica de los estudios de VB para albúmina glicosilada y proporcionar datos actualizados de VB para glucosa y HbA
1c
, incluyendo prestigiosos estudios recientemente publicados como el Estudio de Variación Biológica Europea (EuBIVAS).
Métodos
Se hizo una búsqueda bibliográfica sistemática para identificar estudios sobre VB, encontrándose 9 estudios no incluidos en la primera revisión: 4 para albúmina glicosilada, 3 para glucosa y 3 para HbA
1c
. Se realizó una evaluación crítica de los estudios relevantes, utilizando la herramienta
Biological Variation Data Critical Appraisal Checklist
(BIVAC). Se obtuvieron los estimados globales de VB mediante meta-análisis de los estudios que cumplían los requisitos BIVAC, realizados en individuos sanos con estudios de diseño similar.
Resultados
Un estudio recibió el grado A, dos el B y 6 el C. en la mayoría de los casos el grado C se asoció a deficiencias en el análisis estadístico de los datos. Los estimados de VB para albúmina glicosilada fueron: CV
I
= 1,4%(1,2–2,1) y CV
G
= 5,7%(4,7–10,6); para HbA
1c
, CV
I
= 1,2%(0,3–2,5), CV
G
= 5,4%(3,3–7,3) y para glucosa, CV
I
= 5,0%(4,1–12,0), CV
G
= 8,1%(2,7–10,8) no difirieron de los estimados globales previamente descritos.
Conclusiones
La evaluación crítica y clasificación de los estudios de VB a tenor de su calidad metodológica, seguido de un meta-análisis, genera estimados de VB robustos y fiables. Este estudio proporciona datos de VB para albúmina glicolisada, glucosa y HbA
1c
actualizados y basados en la evidencia científica.
Numerous 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 HbA
, including recently published high-quality studies such as the European Biological Variation study (EuBIVAS).
Systematic 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 HbA
. 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.
One 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: CV
=1.4% (1.2-2.1) and CV
=5.7% (4.7-10.6), whereas estimates for HbA
, CV
=1.2% (0.3-2.5), CV
=5.4% (3.3-7.3), and glucose, CV
=5.0% (4.1-12.0), CV
=8.1% (2.7-10.8) did not differ from previously published global estimates.
The 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 HbA
.
The objective of the present study was to examine the evolution of the analytical performance specifications (APS) used in External Quality Assurance (EQA) schemes, as well as the efficacy of a ...category 1 EQA scheme in monitoring the harmonization of clinical laboratory results in Spain.
A review of the literature on the types of quality specifications used in schemes in other countries and their evolution was performed. In addition, a comparative analysis of the potential impact that different APS from eight countries had on clinical decision-making was made based on three measurands: sodium, thyroid-stimulating hormone (TSH), and activated partial thromboplastin time (aPTT).
Harmonization of analytical methods was demonstrated by assessing whether average results deviated from the certified reference value of control materials within the APS derived from biological variation (BV). The APS used in EQA have evolved from state-of-the-art models to BV. Poor clinical decision-making would occur if the results accepted by some APS were applied.
In Spain, only 2 of the 18 measurands studied are considered to be well harmonized. Closer collaboration between laboratories and analytical system providers would be required to resolve discrepancies.
To assess the frequency of class 1 integrons among isolates of Salmonella enterica producing different types of beta-lactamases from the health region of Tortosa, and to attempt to establish the ...resistance genes located within their variable regions.
The presence of class 1 integrons and of aadA1, aadA2, dfrA1, tem-1, oxa-1 and pse-1 resistance genes within their variable regions was investigated by PCR in 100 ampicillin-resistant isolates of S. enterica (30 S. enteritidis, 56 S. Typhimurium and 14 from other serotypes) consecutively recovered in our laboratory between 2000 and 2001. Beta-lactamases were characterized by isoelectric focusing and PCR.
a) 6/57 TEM-1 producing isolates carried integrons: 1 S. ser Panama, 2 S. ser Enteritidis and 1 S. ser Typhimurium (1600 pb/aadA1-dfrA1); 1 S. ser Panama (1600 pb/aadA2-dfrA1); 1 S. ser Grumpensis (1500 pb 1 1700 pb; aadA2 and ??) b) All OXA-1 producing isolates (20 S. ser Typhimurium) bore an integron of 2000 pb/aadA1-oxa-1; c) All PSE-1 producing isolates (22 S. ser Typhimurium, most of them 104 phage type, and 1 S. enterica immobile 4,12:-:-) harbored 2 integrons (1000 pb/aadA1 and 1,00 pb/pse-1).
The presence of class 1 integrons carrying oxa-1 or pse-1 resistance genes in all the OXA-1-producing and PSE-1-producing isolates investigated could have contributed to their spread and explain the increase in frequency of multiresistant S. ser Typhimurium isolates harboring these enzymes seen in the health region of Tortosa. In addition, we report the first isolate of S. ser enterica serotype Grumpensis harboring integrons.
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