Within-subject biological variation estimates using an indirect data mining strategy. Spanish multicenter pilot study (BiVaBiDa).

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 CVI estimates and calculate confidence intervals (CI), using the EFLM-BVD CVI 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 CVI 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 CVI value was obtained. CONCLUSIONS: Our study presents a new strategy for obtaining robust CVI estimates using an indirect method together with the value of symmetric RCV to select the target population. The CVI 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.

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

Objectives: 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 HbA1c, including recently published high-quality studies such as the European Biological Variation study (EuBIVAS). Methods: 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 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. Results: 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: 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. Conclusions: 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 HbA1c.

Impact of implementing a category 1 external quality assurance scheme for monitoring harmonization of clinical laboratories in Spain.

Background: 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. Methods: 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). Results: 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. Conclusions: 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.

Systematic review and meta-analysis of within-subject and between-subject biological variation estimates of 20 haematological parameters.

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.

[Class 1 integrons among Salmonella enterica isolates producing different types of beta-lactamases from the health region of Tortosa (Spain)]. / Integrones de clase 1 en aislados de Salmonella enterica productores de diferentes tipos de betalactamasas recogidos en la región sanitaria de Tortosa.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Integrones de clase 1 en aislados de Salmonella enterica productores de diferentes tipos de betalactamasas recogidos en la región sanitaria de Tortosa / Class 1 integrons among Salmonella enterica isolates producing different types of beta-lactamases from the health region of Tortosa (Spain)

Objetivo. Estudiar la frecuencia de integrones de clase 1 en aislados de Salmonella enterica productores de diferentes tipos de betalactamasas recogidos en la región sanitaria de Tortosa e intentar determinar los genes de resistencia que llevan insertados. Métodos. Se investigó mediante reacción en cadena de la polimerasa (PCR) la presencia de integrones de clase 1 y de los genes aadA1, aadA2, dfrA1, tem-1, oxa-1 y pse-1 en la región variable de éstos, en 100 aislados de S. enterica (30 S. enteritidis, 56 S. ser Typhimurium y 14 de otros serotipos) resistentes a ampicilina recuperados consecutivamente en nuestro laboratorio entre 2000 y 2001. Las betalactamasas se caracterizaron por isoelectroenfoque y PCR. Resultados. a) 6/57 aislados productores de TEM-1 presentaban integrones: 1 S. ser Panama, 2 S. ser Enteritidis y 1 S. ser Typhimurium (1.600 pb/aadA1-dfrA1); 1 S. ser Panama (1.600 pb/aadA2-dfrA1); 1 S. ser Grumpensis (1.500 pb 1 1.700 pb; aadA2 y ??); b) todos los aislados productores de OXA-1 (20 S. ser Typhimurium) transportaban un integrón de 2.000 pb/aadA1-oxa-1. c) todos los aislados productores de PSE-1 (22 S. ser Typhimurium, la mayoría fagotipo 104, y 1 S. enterica inmóvil [4,12:-:-]) contenían 2 integrones (1.000 pb/aadA1 y 1.200 pb/pse-1). Conclusión. La presencia de integrones que transportaban los genes oxa-1 o pse-1 en todos los aislados estudiados productores de OXA-1 y PSE-1 podría haber facilitado su diseminación y explicar el incremento de aislados multirresistentes de S. ser Typhimurium portadores de estas enzimas en la región sanitaria de Tortosa. Se describe, asimismo, por primera vez la presencia de integrones en un aislado del serotipo Grumpensis (AU)

Objective. 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. Methods. 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. Results. 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). Conclusion. 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 (AU)