Estudio de magnitudes bioquímicas y polimorfismos genéticos en la evolución ósea del hiperparatiroidismo primario tras paratiroidectomía

Consultable des del TDXTítol obtingut de la portada digitalitzadaEl hiperparatiroidismo primario es una enfermedad cuya prevalencia oscila entre el 1 y el 3 en la población adulta. Su incidencia anual es de 250 nuevos casos por millón de habitantes y año. Afecta sobre todo a adultos (el 85 % de los casos tienen más de 30 años), siendo mayor su frecuencia en la séptima década y en mujeres postmenopáusicas. Es dos veces más frecuente en las mujeres que en los varones. Es conocido que no tratar el hiperparatiroidismo primario puede provocar, con el tiempo, enfermedades como la osteopenia y osteoporosis, entre otras. Por ello, siempre que es factible y se cumplen una serie de requisitos, el tratamiento de elección para erradicar esta enfermedad es la paratiroidectomía. Para valorar la respuesta al tratamiento y la evolución de esta enfermedad, podría ser útil estudiar diversas magnitudes biológicas relacionadas con el hueso y la realización de densitometrías óseas, antes y después de la paratiroidectomía, así como llevar a cabo estudios de asociación de diversos polimorfismos genéticos relacionados con el hueso

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

Multicenter evaluation of a new electrochemiluminescence immunoassay for everolimus concentrations in whole blood

Background: The precise monitoring of everolimus, an immunosuppressant drug, is vital for transplant recipients due to its narrow therapeutic range. This study evaluated the analytical performance of a new electrochemiluminescence immunoassay (ECLIA) for everolimus concentrations in whole blood. Methods: Accuracy, imprecision, and sensitivity studies for the Roche Elecsys everolimus ECLIA were performed at 5 European laboratories. The ECLIA was compared with liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods, as well as the Quantitative Microsphere System everolimus assay. Results: Everolimus ECLIA accuracies were within the range 100% +/- 9%. Coefficients of variation (CVs) across the target range were <= 4.8% for repeatability and <= 8.4% for intermediate imprecision, whereas multisite reproducibility at lower (2.71 mcg/L) and higher everolimus concentrations (3.0-30.0 mcg/L) resulted in CVs of <= 13.7% and <= 12.4%, respectively. The CV at the assay's lower limit of quantification without considering bias was excellent, estimated as <= 9.3% at 0.5 mcg/L. The weighted Deming regression analysis, used for comparison of the results obtained by everolimus ECLIA and by LC-MS/MS methods, yielded a slope of 1.21 [95% confidence interval (CI): 1.15-1.26], intercept of 0.478 mcg/L (95% CI: 0.241-0.716), and a Pearson correlation coefficient (r) of 0.91. A single-site comparison between the ECLIA and the Quantitative Microsphere System assay revealed a slope of 1.05 (95% CI: 0.917-1.17), intercept of 1.03 mcg/L (95% CI: 0.351-1.70), and r of 0.91. Conclusions: Based on these results, the Roche Elecsys everolimus ECLIA can be considered suitable for routine therapeutic drug monitoring. A positive bias was observed with respect to LC-MS/MS methods, suggesting that it may be necessary to rebaseline individual patients when switching from LC-MS/MS to the ECLIA; however, this must also be considered for any change of method for everolimus measurement

Predictive Factors of Piperacillin Exposure and the Impact on Target Attainment after Continuous Infusion Administration to Critically Ill Patients

Critically ill patients undergo significant pathophysiological changes that affect antibiotic pharmacokinetics. Piperacillin/tazobactam administered by continuous infusion (CI) improves pharmacokinetic/pharmacodynamic (PK/PD) target attainment. This study aimed to characterize piperacillin PK after CI administration of piperacillin/tazobactam in critically ill adult patients with preserved renal function and to determine the empirical optimal dosing regimen. A total of 218 piperacillin concentrations from 106 patients were simultaneously analyzed through the population PK approach. A two-compartment linear model best described the data. Creatinine clearance (CLCR) estimated by CKD-EPI was the covariate, the most predictive factor of piperacillin clearance (CL) interindividual variability. The mean (relative standard error) parameter estimates for the final model were: CL: 12.0 L/h (6.03%); central and peripheral compartment distribution volumes: 20.7 L (8.94%) and 62.4 L (50.80%), respectively; intercompartmental clearance: 4.8 L/h (26.4%). For the PK/PD target of 100% fT(>1xMIC), 12 g of piperacillin provide a probability of target attainment > 90% for MIC 100 mL/min. For 100% fT(>4xMIC), the highest dose (24 g/24 h) was not sufficient to ensure adequate exposure, except for MICs of 1 and 4 mg/L. Our model can be used as a support tool for initial dose guidance and during therapeutic drug monitoring

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

Multicenter Evaluation of a New Electrochemiluminescence Immunoassay for Everolimus Concentrations in Whole Blood.

BACKGROUND: The precise monitoring of everolimus, an immunosuppressant drug, is vital for transplant recipients due to its narrow therapeutic range. This study evaluated the analytical performance of a new electrochemiluminescence immunoassay (ECLIA) for everolimus concentrations in whole blood. METHODS: Accuracy, imprecision, and sensitivity studies for the Roche Elecsys everolimus ECLIA were performed at 5 European laboratories. The ECLIA was compared with liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods, as well as the Quantitative Microsphere System everolimus assay. RESULTS: Everolimus ECLIA accuracies were within the range 100% ± 9%. Coefficients of variation (CVs) across the target range were ≤4.8% for repeatability and ≤8.4% for intermediate imprecision, whereas multisite reproducibility at lower (2.71 mcg/L) and higher everolimus concentrations (3.0-30.0 mcg/L) resulted in CVs of ≤13.7% and ≤12.4%, respectively. The CV at the assay's lower limit of quantification without considering bias was excellent, estimated as ≤9.3% at 0.5 mcg/L. The weighted Deming regression analysis, used for comparison of the results obtained by everolimus ECLIA and by LC-MS/MS methods, yielded a slope of 1.21 [95% confidence interval (CI): 1.15-1.26], intercept of 0.478 mcg/L (95% CI: 0.241-0.716), and a Pearson correlation coefficient (r) of 0.91. A single-site comparison between the ECLIA and the Quantitative Microsphere System assay revealed a slope of 1.05 (95% CI: 0.917-1.17), intercept of 1.03 mcg/L (95% CI: 0.351-1.70), and r of 0.91. CONCLUSIONS: Based on these results, the Roche Elecsys everolimus ECLIA can be considered suitable for routine therapeutic drug monitoring. A positive bias was observed with respect to LC-MS/MS methods, suggesting that it may be necessary to rebaseline individual patients when switching from LC-MS/MS to the ECLIA; however, this must also be considered for any change of method for everolimus measurement

Multicenter analytical evaluation of the automated electrochemiluminescence immunoassay for cyclosporine

BACKGROUND:: Cyclosporine A (CsA) is used as a posttransplantation immunosuppressant drug, and careful monitoring of CsA concentration in whole blood is essential. A new automated electrochemiluminescence immunoassay (ECLIA) for CsA measurement has been assessed in a multicenter evaluation. METHODS:: Residual EDTA whole blood samples from patients undergoing CsA therapy after organ transplant were used in assay evaluation at 5 clinical laboratories in Europe. Experiments included imprecision according to CLSI EP5-A2 (within-run and intermediate), lower limit of quantification, linearity according to CLSI EP6-A, and recovery of commercial external quality control samples. In addition, comparisons to liquid chromatography-tandem mass spectrometry methods in routine use at each investigational site and to commercial chemiluminescent microparticle immunoassay and antibody-conjugated magnetic immunoassay methods were performed. RESULTS:: Imprecision testing gave coefficients of variation of less than 9% in the 30-2000 mcg/L range for both within-run and intermediate imprecision. Lower limit of quantification of 6.8 mcg/L at one investigational site and 1.8 mcg/L at a second site at 20% coefficient of variation were observed. Linearity was measured over the concentration range 0-2000 mcg/L, yielding a deviation of less than ±12%. External quality control sample recovery by ECLIA was 93%-114% of LC-MS/MS sample recovery. Deming regression analysis of ECLIA method comparison to combined LC-MS/MS results yielded a slope of 1.04 [95% confidence interval (CI), 1.03-1.06] and intercept of 2.8 mcg/L (95% CI, 1.5-4.1 mcg/L). Comparison to chemiluminescent microparticle immunoassay yielded a slope of 0.87 (95% CI, 0.85-0.89) and intercept of 1.4 mcg/L (95% CI, -0.89 to 3.7 mcg/L); comparison to antibody-conjugated magnetic immunoassay yielded a slope of 0.96 (95% CI, 0.93-0.98) and intercept of -4.2 mcg/L (95% CI, -7.1 to -1.2 mcg/L). CONCLUSIONS:: The data from this multicenter evaluation indicate that the new ECLIA-based cyclosporine assay is fit for its purpose, the therapeutic monitoring of CsA