Assessment of plasma voriconazole concentrations in clinical practice

Introducción: Voriconazol presenta una alta variabilidad interindividual en sus concentraciones plasmáticas (Cp). Los objetivos son: (i) describir sus Cp en una cohorte adulta, (ii) estudiar sus potenciales causas de variabilidad y (iii) relacionarlas con las recomendaciones de monitorización farmacocinética actuales. Método: Estudio observacional retrospectivo, incluyendo pacientes con ≥1 determinación de Cp mínima (Cmin) de voriconazol durante 2017. Resultados: Se analizaron 165 Cmin correspondientes a 51 pacientes. La mediana de Cmin fue de 2,4μg/mL (IQR:1,4-3,6), siendo 4μg/mL en 34. Se observaron Cmin significativamente superiores en >65 años (p=0,006) y en pacientes con albúmina <27g/L (p<0,001). Siguiendo las recomendaciones de monitorización de las Cp de voriconazol según la guía ESCMID-ECMM-ERS, se detectarían el 91,1% de Cmin que resultaron fuera de inter¬valo. Conclusiones: Observamos un 36,4% de las Cmin de voriconazol fuera del intervalo óptimo. Identificamos la edad y la concentración de albúmina como factores que influencian las Cp.Introduction: Voriconazole presents a high interindividual variability in plasma concentrations. We aimed to: (i) describe plasma voriconazole concentrations (PVC) of an adult cohort, (ii) identify potential causes of variability and (iii) relate them with current pharmacokinetic monitoring recommendations. Method: Observational retrospective study. All patients with at least one determination of PVC during 2017 were included. Results: A total of 165 trough concentrations (Ctrough) were analyzed from 51 patients. The median Ctrough was 2.4μg/mL (IQR:1.4-3.6). Ctrough were 4 μg/mL in 34. Significantly higher concentrations were ob¬served in patients older than 65 years (p=0.006) and in patients with albumin levels <27g/L (p<0.001). Following PVC’s monitoring recommendation from ESCMID-ECMM-ERS’s guideline, we would detect the 91.1% of Ctrough out of the interval. Conclusions: We observed 36.4% of PVC outside of its optimal range. We identified age and albumin concentration as factors that influence PV

Espacio de Formación Integral «Mentorías Intergeneracionales»: una estrategia de educación integral y colaborativa

En el ámbito universitario, la extensión y las prácticas integrales son ejes fundamentales de la formación actual. En enseñanza primaria y media el desarrollo de proyectos de investigación y el pensamiento computacional son efectivos en promover el aprendizaje incorporando la creatividad. En esta propuesta combinamos estas aproximaciones en ámbitos de trabajo colaborativo entre estudiantes y docentes, para potenciar los procesos de aprendizaje. Con esta meta, docentes de la Universidad de la República (Facultad de Ciencias, Centro Universitario Regional del Este y Centro Universitario Regional Rivera) junto a docentes del Plan Ceibal generaron un Espacio de Formación Integral (EFI) denominado «Mentorías intergeneracionales». El objetivo fue contribuir a la formación integral de los y las estudiantes universitarios y enriquecer los proyectos de investigación de los estudiantes de educación primaria y media desarrollados en el marco del Programa Ceilab. Estudiantes universitarios actuaron como mentores y mentoras de proyectos de niños, niñas y adolescentes de educación pública participantes del Programa Ceilab con asesoría de los y las docentes. Se abordaron temas vinculados a las ciencias ambientales y patrimoniales, utilizando tecnologías digitales (ej. sensores fisicoquímicos, placas programables Micro:bit). El desarrollo del EFI permitió el intercambio entre estudiantes y docentes universitarios, de educación media y del Plan Ceibal, así como el desarrollo de recursos educativos y diversas actividades emergentes. Se describen aquí los resultados obtenidos, los avances y dificultades, así como las formas de trabajar con ellas. Se incluye el análisis de resultados de cuestionarios realizados a estudiantes y docentes participantes. En términos generales, la experiencia enriqueció a los y las participantes. Los desafíos estuvieron asociados principalmente a la figura de mentor/a y a la dificultad de acompasar las dinámicas de los grupos de niños, niñas y adolescentes

Creatine Kinase Elevation in Autosomal Dominant Polycystic Kidney Disease Patients on Tolvaptan Treatment

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cause of end-stage kidney disease. Currently, tolvaptan is the only treatment that has proven to delay disease progression. The most notable side effect of this therapy is drug-induced liver injury; however, recently, there have been two reports of creatine kinase (CK) elevation in ADPKD patients on tolvaptan treatment. We set out to monitor and determine the actual incidence of CK elevation and evaluate its potential association with other clinical factors. Methods: This is an observational retrospective multicenter study performed in rapidly progressive ADPKD patients on tolvaptan treatment from Barcelona, Spain. Laboratory tests, demographics, treatment dose, and reported symptoms were collected from October 2018 to March 2021. Results: Ninety-five patients initiated tolvaptan treatment during follow-up. The medication had to be discontinued in 31 (32.6%) patients, primarily due to aquaretic effects (12.6%), elevated liver enzymes (8.4%), and symptomatic or persistently elevated CK levels (3.2%). Moreover, a total of 27 (28.4%) patients had elevated CK levels, with most of them being either transient (12.6%), mild and asymptomatic (4.2%), or resolved after dose reduction (3.2%) or temporary discontinuation (2.1%). Conclusion: We pre-sent the largest cohort that has monitored CK levels in a real-life setting, finding them elevated in 28.4% of patients. More research and monitoring will help us understand the clinical implications and the pathophysiological mechanism of CK elevation in this population

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Serviço/trabalho social com meninos e meninas com necessidades educativas especiais na Espanha

The article presents the reality of the Service/Social Work in the educational field in Spain with respect to the centers/services in which it is integrated, needs it serves, functions performed and future expectations. In order to achieve the planned objectives, an empirical research was carried out with a mixed methodology (quantitative and qualitative), through document analysis, the administration of questionnaires to professionals, the conduct of individual and group interviews with experts. A total of 30 Labor/Social Service professionals participated in the research and work in the educational field in the southeast of Spain (provinces of Almería, Alicante and Murcia). The results achieved allow us to approach the reality of the Work / Social Service in the educational field in the Southeast of Spain. The research shows that the professional profile is characterized by a feminization of the population with an average age of between 31 and 51 years; the centers and services in which they are integrated are in their majority of public dependence, mainly in Educational Guidance Teams; they attend needs such as school absenteeism, family orientation, attention to diversity and special educational needs; its functions are intended to prevent and address individual problems of the students, in relation to the family and school context; There is a scarce presence of social workers in the education system, as well as a lack of recognition of this professional figure in education.El articulo presente la realidad del Servicio /Trabajo Social en el ámbito educativo en España respecto de los centros/servicios en los que se integra, necesidades que atiende, funciones desempeñadas y expectativas de futuro. Para la consecución de los objetivos previstos se ha realizado una investigación empírica con una metodología mixta (cuantitativa y cualitativa), mediante el análisis documental, la administración de cuestionarios a profesionales, la realización de entrevistas individuales y grupales a expertos. En la investigación han participado un total de 30 profesionales del Trabajo/Servicio Social que desempeñan su labor en el ámbito educativo en el sureste de España (provincias de Almería, Alicante y Murcia). Los resultados alcanzados permiten aproximarnos a la realidad del Trabajo/Servicio Social en el ámbito educativo en el Sureste de España. De la investigación se constata que el perfil profesional se caracteriza por una feminización de la población con un edad promedio de entre 31 y 51 años; los centros y servicios en los que se integran son en su mayoría de dependencia pública, principalmente en Equipos de Orientación Educativa; atienden necesidades como el absentismo escolar, orientación familiar, atención a la diversidad y necesidades educativas especiales; sus funciones van destinadas a prevenir y atender problemáticas individuales de los/as alumnos/as, en relación a los contexto familiar y escolar; existe una escasa presencia de trabajadores/as sociales en el sistema educativo, así como una falta de reconocimiento de esta figura profesional en educación.O artigo apresenta a realidade do Serviço/Trabalho Social na área educacional da Espanha no que diz respeito aos centros/serviços que os integram, as necessidades que atendem, as funções desempenhadas e as expectativas de futuro. Para atingir os objetivos planejados, foi realizada uma pesquisa empírica com metodologia mista (quantitativa e qualitativa), por meio de análise documental, aplicação de questionários e a realização de entrevistas individuais e coletivas com especialistas. Participaram da pesquisa um total de 30 profissionais do Serviço/Trabalho Social que desempenham suas atividades no campo educacional no sudeste da Espanha (municípios de Almería, Alicante e Múrcia). Os resultados alcançados nos permitem aproximar da realidade do Serviço/Trabalho Social, no campo educacional revelando um perfil profissional caracterizado pela feminização, com idade média entre 31 e 51 anos; os centros e serviços nos quais estes profissionais estão integrados são, em sua maioria, de dependência pública, principalmente as equipes de orientação educacional; atendem necessidades como evasão escolar, orientação familiar, atenção à diversidade e necessidades educacionais especiais; suas funções visam prevenir e abordar problemas individuais dos alunos, em relação ao contexto familiar e escolar; há uma escassa presença de assistentes sociais no sistema educacional, bem como a falta de reconhecimento dessa figura profissional na educação

Serviço/trabalho social com meninos e meninas com necessidades educativas especiais na Espanha

The article presents the reality of the Service/Social Work in the educational field in Spain with respect to the centers/services in which it is integrated, needs it serves, functions performed and future expectations. In order to achieve the planned objectives, an empirical research was carried out with a mixed methodology (quantitative and qualitative), through document analysis, the administration of questionnaires to professionals, the conduct of individual and group interviews with experts. A total of 30 Labor/Social Service professionals participated in the research and work in the educational field in the southeast of Spain (provinces of Almería, Alicante and Murcia). The results achieved allow us to approach the reality of the Work / Social Service in the educational field in the Southeast of Spain. The research shows that the professional profile is characterized by a feminization of the population with an average age of between 31 and 51 years; the centers and services in which they are integrated are in their majority of public dependence, mainly in Educational Guidance Teams; they attend needs such as school absenteeism, family orientation, attention to diversity and special educational needs; its functions are intended to prevent and address individual problems of the students, in relation to the family and school context; There is a scarce presence of social workers in the education system, as well as a lack of recognition of this professional figure in education.O artigo apresenta a realidade do Serviço/Trabalho Social na área educacional da Espanha no que diz respeito aos centros/serviços que os integram, as necessidades que atendem, as funções desempenhadas e as expectativas de futuro. Para atingir os objetivos planejados, foi realizada uma pesquisa empírica com metodologia mista (quantitativa e qualitativa), por meio de análise documental, aplicação de questionários e a realização de entrevistas individuais e coletivas com especialistas. Participaram da pesquisa um total de 30 profissionais do Serviço/Trabalho Social que desempenham suas atividades no campo educacional no sudeste da Espanha (municípios de Almería, Alicante e Múrcia). Os resultados alcançados nos permitem aproximar da realidade do Serviço/Trabalho Social, no campo educacional revelando um perfil profissional caracterizado pela feminização, com idade média entre 31 e 51 anos; os centros e serviços nos quais estes profissionais estão integrados são, em sua maioria, de dependência pública, principalmente as equipes de orientação educacional; atendem necessidades como evasão escolar, orientação familiar, atenção à diversidade e necessidades educacionais especiais; suas funções visam prevenir e abordar problemas individuais dos alunos, em relação ao contexto familiar e escolar; há uma escassa presença de assistentes sociais no sistema educacional, bem como a falta de reconhecimento dessa figura profissional na educação.El articulo presente la realidad del Servicio /Trabajo Social en el ámbito educativo en España respecto de los centros/servicios en los que se integra, necesidades que atiende, funciones desempeñadas y expectativas de futuro. Para la consecución de los objetivos previstos se ha realizado una investigación empírica con una metodología mixta (cuantitativa y cualitativa), mediante el análisis documental, la administración de cuestionarios a profesionales, la realización de entrevistas individuales y grupales a expertos. En la investigación han participado un total de 30 profesionales del Trabajo/Servicio Social que desempeñan su labor en el ámbito educativo en el sureste de España (provincias de Almería, Alicante y Murcia). Los resultados alcanzados permiten aproximarnos a la realidad del Trabajo/Servicio Social en el ámbito educativo en el Sureste de España. De la investigación se constata que el perfil profesional se caracteriza por una feminización de la población con un edad promedio de entre 31 y 51 años; los centros y servicios en los que se integran son en su mayoría de dependencia pública, principalmente en Equipos de Orientación Educativa; atienden necesidades como el absentismo escolar, orientación familiar, atención a la diversidad y necesidades educativas especiales; sus funciones van destinadas a prevenir y atender problemáticas individuales de los/as alumnos/as, en relación a los contexto familiar y escolar; existe una escasa presencia de trabajadores/as sociales en el sistema educativo, así como una falta de reconocimiento de esta figura profesional en educación

Genetic population structure in Nacella magellanica: evidence of rapid range expansion throughout the entire species distribution on the Atlantic coast

Nacella magellanica, the most abundant limpet in the Magellanic biogeographic Province of Argentina and Chile, is characterized by a noticeable variability in shell morphology and color patterns. Ecological as well as evolutionary features make this limpet an interesting species for evolutionary and population genetic studies. Here, arbitrary nuclear molecular markers, inter-simple sequence repeat-PCR, are used to analyze the population genetic structure in 14 localities of N. magellanica along 2900 km on the Atlantic coast of the Magellanic Province. We compare the present results, based on nuclear markers, with previous findings of a phylogeographic study that used the mitochondrial COI gene. All the results presented here suggest little genetic structure within N. magellanica, with moderate to high genetic connectivity among populations. The short time elapsed since the expansion of this species plus a possible long larval lifespan and the oceanographic and environmental conditions of the Magellanic Province might explain the lack of genetic structuring and the low levels of genetic differentiation in the species throughout its distribution range along the Argentine coast.Fil: de Aranzamendi, Maria Carla. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Diversidad y Ecologia Animal; ArgentinaFil: Bastida, Ricardo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Gardenal, Cristina Noemi. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Diversidad y Ecologia Animal; Argentin

Exposure-response modeling of tocilizumab in rheumatoid arthritis using continuous composite measures and their individual components

Aims: Tocilizumab has a direct effect on inflammatory markers. Therefore, composite measures for disease activity assessment in rheumatoid arthritis (RA) using these inflammatory markers may not be suitable for tocilizumab treatment. We used a modelling approach to describe the tocilizumab exposure-response relationship and to investigate the different dynamics of the individual components of the routinely used continuous composite measures. Methods: Pharmacokinetic (PK), clinical and laboratory data were obtained from a prospective, observational, single-centre study involving 35 subjects with RA treated with intravenous tocilizumab. A population PK/pharmacodynamic analysis was performed using nonlinear mixed effects models. Results: The population for model development comprised 1086, 1083 and 1082 observations calculated with the disease activity score based on 28 joint (DAS28) and the simplified and clinical disease activity scores (SDAI, CDAI). The tocilizumab exposure-response relationship was described with an indirect-response model. Two main groups of individual components were identified based on their different dynamics under tocilizumab treatment: (i) tender and swollen joint counts and patient and evaluator global assessment showed a slower decrease of their baseline value (half-life: 4.6 weeks, RSE: 24%) and the need for higher serum drug concentration (EC 50: 4.60 μg/mL, RSE: 103%, IIV: 359%) than (ii) C-reactive protein and erythrocyte sedimentation rate (half-life: 2.3 weeks, RSE 19%; EC 50: 0.878 μg/mL, RSE: 41%, IIV: 238%). Conclusion: Our study confirms a different dynamics of the individual components of the most frequently used continuous composite measures under tocilizumab treatment which should be taken into account to avoid misassessment of disease activity