Study of the Stability of Creatine Kinase in Control Materials

Peer Reviewe

Com millorar l'impacte clínic del seguiment terapèutic dels antibiòtics mitjançant la incertesa de mesura

En infeccions osteoarticulars, per subministrar el tractament antibiòtic adequat, evitant de retruc la resistència a aquests, es precisa obtenir resultats de mesura dels antibiòtics el més exactes possible. Entre les estratègies, el Laboratori de Referència d'Enzimologia Clínica (LREC) de la UAB i el Grup d'Infeccions de difícil tractament i ús d'antimicrobians de l'Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), proposen un model per a calcular la incertesa de mesura i avaluar l'impacte del seu coneixement sobre les decisions clíniques.En infecciones osteoarticulares, para suministrar el tratamiento antibiótico adecuado, evitando de rebote la resistencia a estos, se precisa obtener resultados de medida de los antibióticos lo más exactos posible. Entre las estrategias, el Laboratorio de Referencia de Enzimología Clínica (LREC) de la UAB y el grupo de "Infecciones de difícil tratamiento y uso de antimicrobianos" del Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), proponen un modelo para calcular la incertidumbre de medida y evaluar el impacto de su conocimiento sobre las decisiones clínicas.Antibiotic measurement results need to be as accurate as possible in order to provide the proper antibiotic treatment of osteoarticular infections, while avoiding their resistance. Among the strategies, the Clinical Enzymology Reference Laboratory (LREC) of the UAB and the group of "Infections with difficult treatment and use of antimicrobials" of the Bellvitge Biomedical Research Institute (IDIBELL) propose a model for calculating measurement uncertainty and assessing the impact of their knowledge on clinical decisions

Estimation of the measurement uncertainty and practical suggestion for the description of the metrological traceability in clinical laboratories

Clinicians request a large part of measurements of biological quantities that clinical laboratories perform for diagnostic, prognostic or diseases monitoring purposes. Thus, laboratories need to provide patient's results as reliable as possible. Metrological concepts like measurement uncertainty and metrological traceability allow to know the accuracy of these results and guarantee their comparability over time and space. Such is the importance of these two parameters that the estimation of measurement uncertainty and the knowledge of metrological traceability is required for clinical laboratories accredited by ISO 15189:2012. Despite there are many publications or guidelines to estimate the measurement uncertainty in clinical laboratories, it is not entirely clear what information and which formulae they should use to calculate it. On the other hand, unfortunately, there are a small number of clinical laboratories that know and describe the metrological traceability of their results, even though they are aware of the lack of comparability that currently exists for patient's results. Thus, to try to facilitate the task of clinical laboratories, this review aims to provide a proposal to estimate the measurement uncertainty. Also, different suggestions are shown to describe the metrological traceability. Measurement uncertainty estimation is partially based on the ISO/TS 20914:2019 guideline, and the metrological traceability described using the ISO 17511:2020. Different biological quantities routinely measured in clinical laboratories are used to exemplify the proposal and suggestions

Measurement uncertainty of β-lactam antibiotics results: estimation and clinical impact on therapeutic drug monitoring

Background: Despite that measurement uncertainty data should facilitate an appropriate interpretation of measured values, there are actually few reported by clinical laboratories. We aimed to estimate the measurement uncertainty of some β-lactam antibiotics (β-LA), and to evaluate the impact of reporting the measurement uncertainty on clinicians' decisions while guiding antibiotic therapy. Methods: Measurement uncertainty of β-LA (aztreonam [ATM], cefepime [FEP], ceftazidime [CAZ], and piperacillin [PIP]) values, obtained by an UHPLC-MS/MS based-method, was estimated using the top-down approach called the single laboratory validation approach (EUROLAB guidelines). Main uncertainty sources considered were related to calibrators' assigned values, the intermediate precision, and the bias. As part of an institutional program, patients with osteoarticular infections are treated with β-LA in continuous infusion and monitored to assure values at least 4 times over the minimal inhibitory concentration (4×MIC). We retrospectively evaluated the impact of two scenarios of laboratory reports on clinicians' expected decisions while monitoring the treatment: reports containing only the β-LA values, or including the β-LA coverage intervals (β-LA values and their expanded measurement uncertainties). Results The relative expanded uncertainties for ATM, FEP, CAZ and PIP were lower than 26.7%, 26.4%, 28.8%, and 25.5%, respectively. Reporting the measurement uncertainty, we identified that clinicians may modify their decision especially in cases where 4×MIC values were within the β-LA coverage intervals. Conclusions: This study provides a simple method to estimate the measurement uncertainty of β-LA values that can be easily applied in clinical laboratories. Further studies should confirm the potential impact of reporting measurement uncertainty on clinicians' decision-making while guiding antibiotic therapy

Age-Related Serum Biochemical Reference Intervals Established for Unweaned Calves and Piglets in the Post-weaning Period

The purpose of the present study is to establish the influence of age on serum biochemistry reference intervals (RIs) for unweaned calves and recently-weaned piglets using large number of animals sampled at different ages from populations under different season trials. Specifically, milk replacer (MR)-fed calves from April–July 2017 (n = 60); from December 2016–March 2017 (n = 76) and from April–August 2018 (n = 57) and one group of healthy weaned piglets (n = 72) were subjected to the study. Serum enzymes and metabolites of calves at age of 24 h (24 h after colostrum intake), 2, 5, and 7 weeks from merged trials and piglets at 0, 7, and 14 days post-weaning (at 21, 28, and 35 days of age) were studied. The main variable is age whereas no major trial- or sex-biased differences were noticed. In calves, ALT, AST, GGT, GPx, SOD, NEFAs, triglycerides, glucose, creatinine, total protein, and urea were greatly elevated (p < 0.001) at 24 h compared with other ages; glucose, creatinine, total protein, and urea constantly decreased through the age; cholesterol's lowest level (p < 0.001) was found in 24 h compared with other ages and the levels of haptoglobin remained unchanged (p > 0.1) during the study. In comparison with the adult RIs, creatinine from 24 h, NEFAs from 2 w, GGT from 5 w, and urea from 7 w are fully comparable with RIs or lie within RIs determined for adult. In piglets, no changes were noticed on glucose (p > 0.1) and haptoglobin (p > 0.1) and there were no major changes on hepatic enzymes (ALT, AST, and GGT), total protein, creatinine and urea even though several statistical differences were noticed on 7 days post-weaning. Cholesterol, triglycerides, NEFAs, cortisol and PigMAP were found increased (p < 0.05) while TNF-alpha was found less concentrated (p < 0.001) at 0 days post-weaning compared with other times. Moreover, the RIs of creatinine and GGT are fully comparable with RIs or lie within RIs determined for adult. In conclusion, clinical biochemistry analytes RIs were established for unweaned calves and recently-weaned piglets and among them some can vary at different ages

Com millorar l'impacte clínic del seguiment terapèutic dels antibiòtics mitjançant la incertesa de mesura

En infeccions osteoarticulars, per subministrar el tractament antibiòtic adequat, evitant de retruc la resistència a aquests, es precisa obtenir resultats de mesura dels antibiòtics el més exactes possible. Entre les estratègies, el Laboratori de Referència d'Enzimologia Clínica (LREC) de la UAB i el Grup d'Infeccions de difícil tractament i ús d'antimicrobians de l'Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), proposen un model per a calcular la incertesa de mesura i avaluar l'impacte del seu coneixement sobre les decisions clíniques.En infecciones osteoarticulares, para suministrar el tratamiento antibiótico adecuado, evitando de rebote la resistencia a estos, se precisa obtener resultados de medida de los antibióticos lo más exactos posible. Entre las estrategias, el Laboratorio de Referencia de Enzimología Clínica (LREC) de la UAB y el grupo de "Infecciones de difícil tratamiento y uso de antimicrobianos" del Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), proponen un modelo para calcular la incertidumbre de medida y evaluar el impacto de su conocimiento sobre las decisiones clínicas.Antibiotic measurement results need to be as accurate as possible in order to provide the proper antibiotic treatment of osteoarticular infections, while avoiding their resistance. Among the strategies, the Clinical Enzymology Reference Laboratory (LREC) of the UAB and the group of "Infections with difficult treatment and use of antimicrobials" of the Bellvitge Biomedical Research Institute (IDIBELL) propose a model for calculating measurement uncertainty and assessing the impact of their knowledge on clinical decisions

State of affairs and future challenges in laboratory medicine in Spain : an analysis of the Spanish Society of Laboratory Medicine (SEQC ML)

Objectives: Laboratory Medicine is a crucial discipline that contributes to the diagnosis, management and monitoring of patients. This branch of medicine faces two major challenges: New technologies and increased demand. There is limited information available of the state of affairs in Laboratory Medicine in Spain. This study provides a picture of clinical laboratories and clinical laboratory professionals. Methods: The Spanish Society of Laboratory Medicine distributed a questionnaire among the 250 most representative centers (the ones with the largest volume of determinations and training programs), of which 174 (69.6%) returned the questionnaire providing data for 2019. Results :Laboratories were classified according to the number of determinations. In total, 37% identified themselves as small (5 million determinations). The level of specialization of laboratory physicians and laboratory performance were higher in large laboratories. Most requests (87%) and determinations (93%) corresponded to biochemistry and hematology. As many as 63% of physicians had an indefinite contract, and 23% were older than 60 years. Conclusions: Laboratory medicine is a consolidated discipline that is gaining relevance in Spain. It adds value to the diagnosis, prognosis and follow-up of diseases, and to treatment response monitoring. The results of this study will help us address challenges such as the need for specialized training for laboratory professionals; the emergence of technological innovations; exploitation of Big Data; optimization of quality management systems and patient safety

Desarrollo de un sistema para el control de la plausibilidad relacionado con las magnitudes bioquímicas

En la revisión de los resultados de medida de las magnitudes bioquímicas de laboratorio clínico se decide si estos pueden ser entregados al solicitante, es decir "validados", o bien deben ser retenidos y sometidos a una revisión más detallada. Los resultados de medida que no pueden ser entregados durante este proceso se consideran resultados de medida sospechosos. El objetivo de esta tesis es el desarrollo de un sistema para la revisión de resultados de medida de algunas magnitudes bioquímicas de laboratorio clínico, con la finalidad de establecer una forma estandarizada para llevar a cabo esta revisión. El conjunto de procedimientos utilizados para realizar esta revisión se denomina control de la plausiblidad. En esta tesis se desarrollan las herramientas para el control de la plausibilidadque permiten detectar los resultados de medida que se consideran sospechosos debido a que: (a) quedan fuera de unos límites de alerta, que definen un intervalo dentro del que se espera encontrar una gran proporción de resultados de medida de pacientes, (b) no concuerdan con el resultado de medida previo del paciente en cuestión (límites de cambio o deltacheck) (c) o no concuerdan con los resultados de medida de otras magnitudes bioquímicas obtenidos en la misma muestra (límites de predicción). Las magnitudes bioquímicas estudiadas son la concentración en el plasma de: creatininio, urea, albúmina, proteína, alanina-aminotransferasa, aspartato-aminotransferasa, fosfatasa alcalina, γ-glutamiltransferasa, glucosa, ion potasio, ion sodio, tirotropina, tiroxina (libre), ferritina y hierro (II + III). Para la estimación de los límites de alerta, de cambio y de predicción se han utilizado todos los datos correspondientes a los resultados de medida, de las magnitudes bioquímicas seleccionadas, obtenidos en el laboratorio clínico durante un año. Los límites de alerta se han estimado a partir de los percentiles que corresponden a los resultados de medida que excluyen el 10 %, 1 % y el 0,1 % de los resultados de medida. Los límites de cambio se han estimado a partir de los percentiles que corresponden a las diferencias relativas entre dos resultados de medida de un mismo paciente que excluyen el 10 %, 1 % y el 0,1 % de las diferencias relativas calculadas. Los límites de predicción se han estimado a partir de ecuaciones de regresión por el método de mínimos cuadrados para los resultados de medida de las magnitudes bioquímicas relacionadas fisiopatológicamente, estableciendo diferentes intervalos de confianza (90 %, 99 % y 99,9 %). Para asegurar que el modelo de estimación de los límites de alerta, de cambio y de predicción es reproducible en el tiempo, se han aplicado los límites estimados a otro conjunto de datos (resultados de medida de otro año diferente) y se ha verificado que el porcentaje de resultados de medida sospechosos obtenido es similar al porcentaje esperado. Se ha realizado la separación de los límites de alerta y de cambio en dos subgrupos, según la procedencia de los resultados de media sea de pacientes ingresados o ambulatorios, permitiendo adecuar estos límites a cada población a la que se apliquen. Se ha realizado la aplicación simultánea de los límites de alerta, de cambio y de predicción para estudiar el porcentaje de resultados de medida que son considerados como sospechosos por cada límite, observándose que, en general, cada uno de estos límites es útil para detectar resultados de medida sospechosos. Al aplicar los límites de alerta, de cambio y de predicción a los resultados de medida de las magnitudes bioquímicas contenidas en los informes de laboratorio clínico, al aumentar el número de magnitudes bioquímicas incluidas en estos, aumenta la probabilidad de que el resultado de medida de alguna de las magnitudes bioquímicas supere alguno de los límites de alerta, de cambio y de predicción. La aplicación de cada una de las combinaciones de los límites de alerta, cambio y predicción, proporciona un porcentaje diferente de informes de laboratorio sospechosos, y para la selección de los percentiles utilizados en la estimación de estos límites, cada laboratorio clínico ha de establecer que carga de trabajo, derivada de la aplicación de este control de la plausibilidad, puede asumir. Se ha realizado también, un experimento de revisión por inspección visual de los resultados de medida por facultativos especialistas, que pone en evidencia la elevada variabilidad interindividual existente cuando se realiza este proceso de esta forma.In the review of patients' measured results of clinical laboratory quantities, specialists decide if measured results can be delivered to the petitioner, (commonly known validated) or by the contrary, measured results must be retained and reviewed in a more detailed way. The measured results that can not be delivered during this process are considered as doubtful measured results. The objective of this thesis is to develop a system to review measured results of some biochemical quantities commonly measured at clinical laboratories, in order to establish a standardized way to perform this review. The set of procedures used for this review is called plausibility control. In this thesis are developed the main tools in the plausibility control, which allows professionals to detect doubtful measured results because: (a) exceed some alert limits, which define an interval where a large proportion of such measured results can be expected to be found, (b) are not in agreement with the corresponding preceding one using a change limit (change limits or deltacheck), (c) are not in agreement with measured results of other quantities obtained in the same sample (prediction limits). The biochemical quantities studied in this work were the concentration in plasma of the following compounds: creatininium, urea, albumin, protein, alanine-aminotransferase, γ-glutamyltransferase, aspartate-aminotransferase, alkaline phosphatase, glucose, potassium ion, sodium ion, thyrotropin, thyroxine (free), ferritin and iron (II + III). To estimate the alert, change and prediction limits data corresponding to measured results of the biochemical quantities obtained in one year have been used. Alert limits have been estimated through the percentiles corresponding to the results that exclude the 10 %, 1 % and 0,1 % of the measured results. Change limits have been estimated based on the percentiles corresponding to the relative differences between two measured results from the same patient that exclude 10 %, 1 % and 0,1 % of relative differences calculated. Prediction limits have been estimated from regression equations adjusted by the least square method using the measured results of the biochemical quantities related pathophysiology, establishing different confidence intervals (90 %, 99 % and 99,9 %). To assure that the model performed to estimate alert, change and prediction limits was reproducible over time, these limits have been applied to another set of data (measured results of a different year) and it was verified that the percentage of doubtful measured results obtained was similar to the expected one. A separation of the alert and change limits in two subgroups was performed, according to the origin of the measured results: inpatient or outpatient. This separation allowed us to adjust these limits for each group in which they apply. Finally, a simultaneous application of the alert, change and prediction limits was performed in order to study the percentage of doubtful measured results for each limit; once it was performed, we could note that these limits were useful to detect doubtful measured results. The application of alert, change and prediction limits to the measured results of biochemical quantities that are usually included in the laboratory reports, provide an increase of the number of doubtful results, the greater is the number of biochemical quantities included in the report, since the probability of one measured result exceeds any of the these limits is higher. The application of each combination of the alert, change and prediction limits, provides a different percentage of doubtful laboratory reports; therefore, in order to select the percentiles used in the estimation of these limits, each clinical laboratory must decide what workload resulting from the application of the plausibility control, could assume. In addition, an experiment based on reviewing reports by visual inspection of the measured results was performed by laboratory specialists. The experiment demonstrated a high interindividual variability of the process

Estado actual y retos futuros de la medicina de laboratorio en España: un análisis de la Sociedad Española de Medicina de Laboratorio (SEQCML)

La medicina de laboratorio es una disciplina clave que contribuye al diagnóstico, terapia y seguimiento adecuado de los pacientes. Actualmente se enfrenta a grandes retos debido a la innovación tecnológica y al aumento de la demanda. Desafortunadamente hay una información limitada para comprender la situación actual en España. Este estudio pretende mostrar la situación de los laboratorios clínicos y de los profesionales de la medicina laboratorio

State of affairs and future challenges in laboratory medicine in Spain: an analysis of the Spanish Society of Laboratory Medicine (SEQCML)

Laboratory Medicine is a crucial discipline that contributes to the diagnosis, management and monitoring of patients. This branch of medicine faces two major challenges: New technologies and increased demand. There is limited information available of the state of affairs in Laboratory Medicine in Spain. This study provides a picture of clinical laboratories and clinical laboratory professionals