Jesus Frías | Universidad Autónoma de Madrid (original) (raw)
Papers by Jesus Frías
Basic & Clinical Pharmacology & Toxicology, 2015
We conducted a prospective evaluation of nonchemotherapy-induced agranulocytosis (NIA) in a terti... more We conducted a prospective evaluation of nonchemotherapy-induced agranulocytosis (NIA) in a tertiary hospital in Spain. Through our Prospective Pharmacovigilance Program from Laboratory Signals at Hospital, we detected agranulocytosis cases over a period of 42 consecutive months. This report estimates incidence, drug causality, clinical features, outcomes of NIA cases, and assesses laboratory differences with respect to non-NIA. We detected 1,349 cases of agranulocytosis in 538 adult patients; of these, 43 cases in 40 patients were caused by non-chemotherapy drugs. The incidence rate for 10,000 patients during the study period was 2.75 (Poisson Confidence Interval (CI)-95%: 0.62-7.22). The mean (SD) age was 48 (21) years. All cases were categorized as serious, because they required hospitalization (28 cases) or prolongation of hospitalization (15 cases). The outcome was recovery without sequela (39 cases), recovery with sequela (1 case of toe amputation) or death (3 cases, 7%). The most frequent cause of NIA was antimicrobial drugs (19 cases). The highest incidence rate per 10,000 Defined Daily Doses was for cefepime (83.85; Poisson-CI 95%: 67-102.89). Automatic linear modelling (n=75, R(2) =77.9%) showed a significant inverse association with platelets, alkaline phosphatase, C reactive protein, fibrinogen, lactate dehydrogenase and direct to mean corpuscular hemoglobin, and hematocrit. A generalized linear model retained platelets, total serum proteins, creatinine and hemoglobin. The findings suggest an immune-mediated destruction or myeloid toxicity, possibly facilitated by an increase in drug exposure. There might be additional contributing factors, such nutritional deficiencies or chronic diseases, to develop NIA after exposure to a potentially causative drug. This article is protected by copyright. All rights reserved.
Regulatory Toxicology and Pharmacology, 2015
Paracetamol (Acetaminophen) poisoning data can reveal the potential deficiencies of paracetamol p... more Paracetamol (Acetaminophen) poisoning data can reveal the potential deficiencies of paracetamol poisoning management guidelines. We conducted a retrospective cohort study of patients >18years who were attended in the emergency department (ED) of a Spanish tertiary hospital, from 2005 to 2010 for suspected paracetamol overdose and who had measurable paracetamol concentrations. 208 patients suspected of paracetamol poisoning were identified. The annual incidence in the ED increased from 2.0 (95%-CI: 0.2-7.2) cases per 10,000 patients in 2005 to 3.4 (95%-CI: 1.1-8.8) in 2010. Only 7 of 98 patients (7.14%) with acute poisoning at toxic doses showed hepatotoxicity signs, 4 (57.1%) of whom presented acute liver failure (ALF) criteria, while 8 of 10 patients (80%) with chronic paracetamol poisoning at toxic doses presented hepatotoxicity and 3 (37.5%) with ALF criteria. The time required to find medical care was 9.0h for acute poisoning and 49.6h for chronic poisoning…
Clinical Pharmacology & Therapeutics, 2010
Current Therapeutic Research, 2000
Cancer Chemotherapy and Pharmacology, 2005
British Journal of Clinical Pharmacology, 2010
European Journal of Pharmacology, 2010
Frontiers in Pharmacology
Many factors have been described to contribute to voriconazole (VCZ) interpatient variability in ... more Many factors have been described to contribute to voriconazole (VCZ) interpatient variability in plasma concentrations, especially CYP2C19 genetic variability. In 2014, Hicks et al. presented data describing the correlation between VCZ plasma concentrations and CYP2C19 diplotypes in immunocompromised pediatric patients and utilized pharmacokinetic modeling to extrapolate a more suitable VCZ dose for each CYP2C19 diplotype. In 2017, in our hospital, a clinical protocol was developed for individualization of VCZ in immunocompromised patients based on preemptive genotyping of CYP2C19 and dosing proposed by Hicks et al., Clinical Pharmacogenetics Implementation Consortium (CPIC) clinical guidelines, and routine therapeutic drug monitoring (TDM). We made a retrospective review of a cohort of 28 immunocompromised pediatric patients receiving VCZ according to our protocol. CYP2C19 gene molecular analysis was preemptively performed using PharmArray®. Plasma trough concentrations were measur...
Actualidad En Farmacologia Y Terapeutica, 2005
Resumen: El cefditoren es una cefalosporina de tercera generación que se administra por vía oral ... more Resumen: El cefditoren es una cefalosporina de tercera generación que se administra por vía oral en forma de pivoxilo, un profármaco que es hidrolizado por las esterasas intestinales liberando a la circulación la forma activa. El cefditoren posee un amplio ...
... Manejo de antibióticos en el paciente anciano. Información General. Autores: Jesús Frías Inie... more ... Manejo de antibióticos en el paciente anciano. Información General. Autores: Jesús Frías Iniesta; Editores: Madrid : Editores Médicos, DL 1996; Año de publicación: 1996; País: España; Idioma: Español; ISBN : 84-87054-40-4. Otros catálogos. ...
Revista Espanola De Pediatria Clinica E Investigacion, 2004
Información del artículo Bases farmacológicas para el uso de antibióticos en pediatría.
SEMERGEN - Medicina de Familia, 2012
Ibuprofeno; Codeína; Sinergismo Resumen Una de las principales características de una buena combi... more Ibuprofeno; Codeína; Sinergismo Resumen Una de las principales características de una buena combinación farmacológica es la sinergia. Existe en el mercado, desde hace relativamente poco tiempo, una nueva combinación analgésica de ibuprofeno, un antiinflamatorio no esteroideo (AINE) muy usado en la práctica médica diaria por su buen cociente de eficacia y seguridad, y codeína, un opiáceo menor muy utilizado como segundo escalón analgésico en combinación. Hemos realizado una revisión en MEDLINE de los principales estudios publicados en la literatura médica en cuanto a eficacia y seguridad de ambos principios activos por separado, para finalizar con una aproximación tanto de la experiencia clínica mostrada en estudios con combinaciones analgésicas en general, como en las hipótesis de un posible sinergismo entre AINE y opiáceos.
Progresos de Obstetricia y Ginecología, 2008
Técnicas de reproducción asistida. Gonadotropinas. Gonadotropina recombinante humana. Gonadotropi... more Técnicas de reproducción asistida. Gonadotropinas. Gonadotropina recombinante humana. Gonadotropinas urinarias. Metaanálisis.
The Open Ethics Journal, 2009
Objectives: The principal objective of the study was to conduct a descriptive review of 1.000 cli... more Objectives: The principal objective of the study was to conduct a descriptive review of 1.000 clinical trials (CT) evaluated by the Research Ethics Committee (REC) of a universitary hospital the Autonomous Region of Madrid, to define the map of current clinical research and its concordance with official priority lines of investigation in Spain. Methods: This is a prospective and analytic observational study of 1.000 CT, (980 with medicines), whose data were collected during a period of six years (May 1999-May 2005) in the Hospital Universitario La Paz of Madrid. It analyzes the intrinsic characteristics of the 1.000 CT evaluated over this period. Results: For this study, 621 CT are being conducted in the medical area, 99 in pharmacology, 90 in surgery, 87 in pediatrics, 42 in primary care centers, 28 in anesthesia and resuscitation, 25 in obstetrics and gynecology, 13 in central services, and 13 in external centers that are non-dependent on the public health system. Of them, 151 CT are uni-center and 849 multi-center, 490 of which are international. In terms of development phase, 103 are phase I, 128 phase II 468 phase III, and 215 phase IV. Sixty-six observational studies were evaluated, as well as 20 epidemiological studies. In 86%, the sponsor is the pharmaceutical industry. In 597 of the CT, the principal objectives of the study have been to evaluate efficacy and safety. The population in 913 of the CT is adult, and pediatric in the remaining 87. Conclusions: The CT with medicines were the most often evaluated, and the most frequent of those being phase III protocols, multi-centric and international, with primary objectives of efficacy and safety in adult patients, and sponsored almost exclusively by the pharmaceutical industry. The medical attending area of the hospital has the greatest prominence of studies and the priority research lines were infectious diseases, especially HIV infection, prevention of cardiovascular risk, rheumatological pathology, and studies of bioavailability. Genetic studies (pharmacogenetics and investigation of genes responsible for pathologies) have in recent years become an important component of CT.
Medicina Clínica, 2009
La magnitud del problema y sus consecuencias La hipertensió n arterial presenta una prevalencia c... more La magnitud del problema y sus consecuencias La hipertensió n arterial presenta una prevalencia considerable en los países desarrollados, donde afecta a casi el 40% de los
Thrombosis Research, 2014
To estimate the incidence and predictors of symptomatic arterial and venous thromboembolic events... more To estimate the incidence and predictors of symptomatic arterial and venous thromboembolic events (TEE) from intravenous immunoglobulin (IVIg) therapy according to its indications. Methods: We performed a retrospective cohort study of patients seen at our institution and treated with IVIg over a 36-month period. Indications, comorbility and comedication associated with TEE were identified by a stepwise logistic regression analysis. Results: Of 303 patients included with at least one infusion of IVIg over three years, TEE were identified in a total of 50 patients treated with IVIg, for an incidence of 16.9% (CI 95%: 13.0-21.6); 27 (54%) arterial (9.1%;CI 95%: 6.3-13.0%) and 23 (46%) venous TEE (7.8%; CI95%: 5.2-11.4%), overall mortality was 32%. Per indication there were more patients with autoimmune conditions, secondary immunodeficiency, dysimmune neuropathies, acute rejection of solid organ transplantation and sepsis. Patients with TEE were significantly older, were more likely to be men, they had more comorbid conditions; the doses of IVIg were high (589.4 mg/kg/day vs 387.0 mg/kg/day, p b 0.001) and differences in comedication were found. The stepwise logistic regression analysis retained high doses of IVIg (OR 3.03; CI 95%: 1.49-5.67) and diuretics therapy (OR 1.69; CI 95%: 1.06-3.97) when combined with the usual comorbid confounders. Conclusions: The incidence of TEE from IVIg therapy remains high at one in six patients treated. The most remediable factor is a high daily IVIg load. Decreasing the daily IVIg dose together with carefully weighing diuretics therapy and comorbid risk factors may be the keys to saving lives.
Journal of Antimicrobial Chemotherapy, 1994
Journal of Antimicrobial Chemotherapy, 1995
... was performed for theophylline by other authors, reaching a limit of sensitivity of 0.1 mg/L ... more ... was performed for theophylline by other authors, reaching a limit of sensitivity of 0.1 mg/L (Whitehead, Grigurinovich & ... CARLOS GOVANTES-ANTONIO J. CARCAS-JOSE L. GARClA-SATUE* PEDRO ZAPATER' JESUS FRJASrt 'Servicio de Farmacologia Clinica, bServicio ...
Journal of Antimicrobial Chemotherapy, 1994
Progresos de Obstetricia y Ginecología, 2008
In Spain, several different gonadotrophins are available for assisted reproductive techniques. Th... more In Spain, several different gonadotrophins are available for assisted reproductive techniques. The present review aims to determine the differences between these gonadotrophins and to establish the advantages and limitations of each in terms of their ...
Basic & Clinical Pharmacology & Toxicology, 2015
We conducted a prospective evaluation of nonchemotherapy-induced agranulocytosis (NIA) in a terti... more We conducted a prospective evaluation of nonchemotherapy-induced agranulocytosis (NIA) in a tertiary hospital in Spain. Through our Prospective Pharmacovigilance Program from Laboratory Signals at Hospital, we detected agranulocytosis cases over a period of 42 consecutive months. This report estimates incidence, drug causality, clinical features, outcomes of NIA cases, and assesses laboratory differences with respect to non-NIA. We detected 1,349 cases of agranulocytosis in 538 adult patients; of these, 43 cases in 40 patients were caused by non-chemotherapy drugs. The incidence rate for 10,000 patients during the study period was 2.75 (Poisson Confidence Interval (CI)-95%: 0.62-7.22). The mean (SD) age was 48 (21) years. All cases were categorized as serious, because they required hospitalization (28 cases) or prolongation of hospitalization (15 cases). The outcome was recovery without sequela (39 cases), recovery with sequela (1 case of toe amputation) or death (3 cases, 7%). The most frequent cause of NIA was antimicrobial drugs (19 cases). The highest incidence rate per 10,000 Defined Daily Doses was for cefepime (83.85; Poisson-CI 95%: 67-102.89). Automatic linear modelling (n=75, R(2) =77.9%) showed a significant inverse association with platelets, alkaline phosphatase, C reactive protein, fibrinogen, lactate dehydrogenase and direct to mean corpuscular hemoglobin, and hematocrit. A generalized linear model retained platelets, total serum proteins, creatinine and hemoglobin. The findings suggest an immune-mediated destruction or myeloid toxicity, possibly facilitated by an increase in drug exposure. There might be additional contributing factors, such nutritional deficiencies or chronic diseases, to develop NIA after exposure to a potentially causative drug. This article is protected by copyright. All rights reserved.
Regulatory Toxicology and Pharmacology, 2015
Paracetamol (Acetaminophen) poisoning data can reveal the potential deficiencies of paracetamol p... more Paracetamol (Acetaminophen) poisoning data can reveal the potential deficiencies of paracetamol poisoning management guidelines. We conducted a retrospective cohort study of patients >18years who were attended in the emergency department (ED) of a Spanish tertiary hospital, from 2005 to 2010 for suspected paracetamol overdose and who had measurable paracetamol concentrations. 208 patients suspected of paracetamol poisoning were identified. The annual incidence in the ED increased from 2.0 (95%-CI: 0.2-7.2) cases per 10,000 patients in 2005 to 3.4 (95%-CI: 1.1-8.8) in 2010. Only 7 of 98 patients (7.14%) with acute poisoning at toxic doses showed hepatotoxicity signs, 4 (57.1%) of whom presented acute liver failure (ALF) criteria, while 8 of 10 patients (80%) with chronic paracetamol poisoning at toxic doses presented hepatotoxicity and 3 (37.5%) with ALF criteria. The time required to find medical care was 9.0h for acute poisoning and 49.6h for chronic poisoning…
Clinical Pharmacology & Therapeutics, 2010
Current Therapeutic Research, 2000
Cancer Chemotherapy and Pharmacology, 2005
British Journal of Clinical Pharmacology, 2010
European Journal of Pharmacology, 2010
Frontiers in Pharmacology
Many factors have been described to contribute to voriconazole (VCZ) interpatient variability in ... more Many factors have been described to contribute to voriconazole (VCZ) interpatient variability in plasma concentrations, especially CYP2C19 genetic variability. In 2014, Hicks et al. presented data describing the correlation between VCZ plasma concentrations and CYP2C19 diplotypes in immunocompromised pediatric patients and utilized pharmacokinetic modeling to extrapolate a more suitable VCZ dose for each CYP2C19 diplotype. In 2017, in our hospital, a clinical protocol was developed for individualization of VCZ in immunocompromised patients based on preemptive genotyping of CYP2C19 and dosing proposed by Hicks et al., Clinical Pharmacogenetics Implementation Consortium (CPIC) clinical guidelines, and routine therapeutic drug monitoring (TDM). We made a retrospective review of a cohort of 28 immunocompromised pediatric patients receiving VCZ according to our protocol. CYP2C19 gene molecular analysis was preemptively performed using PharmArray®. Plasma trough concentrations were measur...
Actualidad En Farmacologia Y Terapeutica, 2005
Resumen: El cefditoren es una cefalosporina de tercera generación que se administra por vía oral ... more Resumen: El cefditoren es una cefalosporina de tercera generación que se administra por vía oral en forma de pivoxilo, un profármaco que es hidrolizado por las esterasas intestinales liberando a la circulación la forma activa. El cefditoren posee un amplio ...
... Manejo de antibióticos en el paciente anciano. Información General. Autores: Jesús Frías Inie... more ... Manejo de antibióticos en el paciente anciano. Información General. Autores: Jesús Frías Iniesta; Editores: Madrid : Editores Médicos, DL 1996; Año de publicación: 1996; País: España; Idioma: Español; ISBN : 84-87054-40-4. Otros catálogos. ...
Revista Espanola De Pediatria Clinica E Investigacion, 2004
Información del artículo Bases farmacológicas para el uso de antibióticos en pediatría.
SEMERGEN - Medicina de Familia, 2012
Ibuprofeno; Codeína; Sinergismo Resumen Una de las principales características de una buena combi... more Ibuprofeno; Codeína; Sinergismo Resumen Una de las principales características de una buena combinación farmacológica es la sinergia. Existe en el mercado, desde hace relativamente poco tiempo, una nueva combinación analgésica de ibuprofeno, un antiinflamatorio no esteroideo (AINE) muy usado en la práctica médica diaria por su buen cociente de eficacia y seguridad, y codeína, un opiáceo menor muy utilizado como segundo escalón analgésico en combinación. Hemos realizado una revisión en MEDLINE de los principales estudios publicados en la literatura médica en cuanto a eficacia y seguridad de ambos principios activos por separado, para finalizar con una aproximación tanto de la experiencia clínica mostrada en estudios con combinaciones analgésicas en general, como en las hipótesis de un posible sinergismo entre AINE y opiáceos.
Progresos de Obstetricia y Ginecología, 2008
Técnicas de reproducción asistida. Gonadotropinas. Gonadotropina recombinante humana. Gonadotropi... more Técnicas de reproducción asistida. Gonadotropinas. Gonadotropina recombinante humana. Gonadotropinas urinarias. Metaanálisis.
The Open Ethics Journal, 2009
Objectives: The principal objective of the study was to conduct a descriptive review of 1.000 cli... more Objectives: The principal objective of the study was to conduct a descriptive review of 1.000 clinical trials (CT) evaluated by the Research Ethics Committee (REC) of a universitary hospital the Autonomous Region of Madrid, to define the map of current clinical research and its concordance with official priority lines of investigation in Spain. Methods: This is a prospective and analytic observational study of 1.000 CT, (980 with medicines), whose data were collected during a period of six years (May 1999-May 2005) in the Hospital Universitario La Paz of Madrid. It analyzes the intrinsic characteristics of the 1.000 CT evaluated over this period. Results: For this study, 621 CT are being conducted in the medical area, 99 in pharmacology, 90 in surgery, 87 in pediatrics, 42 in primary care centers, 28 in anesthesia and resuscitation, 25 in obstetrics and gynecology, 13 in central services, and 13 in external centers that are non-dependent on the public health system. Of them, 151 CT are uni-center and 849 multi-center, 490 of which are international. In terms of development phase, 103 are phase I, 128 phase II 468 phase III, and 215 phase IV. Sixty-six observational studies were evaluated, as well as 20 epidemiological studies. In 86%, the sponsor is the pharmaceutical industry. In 597 of the CT, the principal objectives of the study have been to evaluate efficacy and safety. The population in 913 of the CT is adult, and pediatric in the remaining 87. Conclusions: The CT with medicines were the most often evaluated, and the most frequent of those being phase III protocols, multi-centric and international, with primary objectives of efficacy and safety in adult patients, and sponsored almost exclusively by the pharmaceutical industry. The medical attending area of the hospital has the greatest prominence of studies and the priority research lines were infectious diseases, especially HIV infection, prevention of cardiovascular risk, rheumatological pathology, and studies of bioavailability. Genetic studies (pharmacogenetics and investigation of genes responsible for pathologies) have in recent years become an important component of CT.
Medicina Clínica, 2009
La magnitud del problema y sus consecuencias La hipertensió n arterial presenta una prevalencia c... more La magnitud del problema y sus consecuencias La hipertensió n arterial presenta una prevalencia considerable en los países desarrollados, donde afecta a casi el 40% de los
Thrombosis Research, 2014
To estimate the incidence and predictors of symptomatic arterial and venous thromboembolic events... more To estimate the incidence and predictors of symptomatic arterial and venous thromboembolic events (TEE) from intravenous immunoglobulin (IVIg) therapy according to its indications. Methods: We performed a retrospective cohort study of patients seen at our institution and treated with IVIg over a 36-month period. Indications, comorbility and comedication associated with TEE were identified by a stepwise logistic regression analysis. Results: Of 303 patients included with at least one infusion of IVIg over three years, TEE were identified in a total of 50 patients treated with IVIg, for an incidence of 16.9% (CI 95%: 13.0-21.6); 27 (54%) arterial (9.1%;CI 95%: 6.3-13.0%) and 23 (46%) venous TEE (7.8%; CI95%: 5.2-11.4%), overall mortality was 32%. Per indication there were more patients with autoimmune conditions, secondary immunodeficiency, dysimmune neuropathies, acute rejection of solid organ transplantation and sepsis. Patients with TEE were significantly older, were more likely to be men, they had more comorbid conditions; the doses of IVIg were high (589.4 mg/kg/day vs 387.0 mg/kg/day, p b 0.001) and differences in comedication were found. The stepwise logistic regression analysis retained high doses of IVIg (OR 3.03; CI 95%: 1.49-5.67) and diuretics therapy (OR 1.69; CI 95%: 1.06-3.97) when combined with the usual comorbid confounders. Conclusions: The incidence of TEE from IVIg therapy remains high at one in six patients treated. The most remediable factor is a high daily IVIg load. Decreasing the daily IVIg dose together with carefully weighing diuretics therapy and comorbid risk factors may be the keys to saving lives.
Journal of Antimicrobial Chemotherapy, 1994
Journal of Antimicrobial Chemotherapy, 1995
... was performed for theophylline by other authors, reaching a limit of sensitivity of 0.1 mg/L ... more ... was performed for theophylline by other authors, reaching a limit of sensitivity of 0.1 mg/L (Whitehead, Grigurinovich & ... CARLOS GOVANTES-ANTONIO J. CARCAS-JOSE L. GARClA-SATUE* PEDRO ZAPATER' JESUS FRJASrt 'Servicio de Farmacologia Clinica, bServicio ...
Journal of Antimicrobial Chemotherapy, 1994
Progresos de Obstetricia y Ginecología, 2008
In Spain, several different gonadotrophins are available for assisted reproductive techniques. Th... more In Spain, several different gonadotrophins are available for assisted reproductive techniques. The present review aims to determine the differences between these gonadotrophins and to establish the advantages and limitations of each in terms of their ...