Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Monthly characterization of the tropospheric circulation over the euro-atlantic area in relation with the timing of stratospheric final warmings

In recent decades, there has been a growing interest in the study of a possible active role of the stratosphere on the tropospheric climate. However, most studies have focused on this connection in wintertime. This paper deals with the possible relationship between variations in the timing of stratospheric final warmings (SFWs, observed in springtime) and monthly averaged changes in the Euro-Atlantic climate. On the basis of the date on which the SFW occurs, two sets of years have been selected for the period of study (1958–2002): “early years” and “late years,” reflecting a very early or a very late breakup of the polar vortex. The statistical significance of the early-minus-late differences in the analyzed fields has been established by applying a nonparametric test based on a Monte Carlo–like technique. Using data from 40-yr European Centre for Medium-Range Weather Forecasts Re-Analysis (ERA-40), a dynamical study for March and April has shown important differences between both sets of years in stationary waves, especially ultralong ones (waves with k = 1 in March and k = 2 in April). Furthermore, the interannual variations in the stratospheric zonal wind seem to propagate downward as the spring progresses, in such a way that they reach tropospheric levels in April. Relevant differences between “early” and “late” years have been found in tropospheric monthly fields in the Euro-Atlantic area (geopotential, zonal wind, and storm-track activity), being at their most extensive in April.Ministerio de Educación y Ciencia (España)Consejeria de Educacion de la Comunidad de MadridEuropean Social FundDepto. de Física de la Tierra y AstrofísicaFac. de Ciencias FísicasTRUEpu

Tropospheric forcing of the stratosphere: A comparative study of the two different major stratospheric warmings in 2009 and 2010

In January 2009 and 2010, two major stratospheric warmings (MSWs) took place in the boreal polar stratosphere. Both MSWs were preceded by nearly the strongest injection of tropospheric wave activity on record since 1958 and their central date was almost coincident. However, the typical external factors that influence the occurrence of MSWs (the Quasi‐Biennial Oscillation, sunspot cycle, or El Niño) were dissimilar in the two midwinters: favorable in 2010 but unfavorable in 2009. In this study, the driving mechanisms of these two different MSWs were investigated focusing on the amplification of upward wave activity injection into the stratosphere before the MSW onset. By decomposing the total wave flux injection into contributions from the climatological planetary waves and from deviations from the latter we found clear differences in this amplification between both MSWs. The pre‐MSW period in 2009 was characterized by a peak in the 100 hPa eddy heat flux with a predominance of wave number 2 activity. This was due to strong anomalies associated with Rossby wave packets originating from a deep ridge over the eastern Pacific. In contrast, the amplification of the upward wave propagation prior to the 2010 MSW was equally due to Rossby wave packets and to the interaction between the latter and the climatological waves. This amplification enhanced wave number 1 stationary waves in January 2010, which seemed at least partially due to the 2009/2010 El Niño event. Our results show the relevance of the internal tropospheric variability in generating MSWs, particularly when the external factors do not play any role.Ministerio de Educación y CienciaDepto. de Física de la Tierra y AstrofísicaFac. de Ciencias FísicasTRUEpu

La fotografía en Educación Infantil

Proyecto destinado a elaborar materiales didácticos para los niños-as de Educación Infantil. Los objetivos son ayudarles a descrubrir y controlar su propio entorno, enriquecer sus posibilidades expresivas mediante el uso de imágenes cercanas, incentivarles por medio de materiales en los que ellos sean los propios protagonistas, y potenciar su desarrollo espacial y visual. La metodología consiste en elaborar murales, libros, puzzles, fichas de trabajo, etc, mediante la utilización de fotografías que traen los niños de casa o bien se hacen en el propio colegio. Las actividades están relacionadas con las vivencias cotidianas de los niños-as. En la evaluación del proyecto se ha utilizado un cuestionario para alumnos, familias y profesores. La motivación e interés ha sido grande y la participación en cuanto a uso de materiales y desarrollo de actividaees ha sido alta. Se recogen fotografías sobre las actividades realizadas..Madrid (Comunidad Autónoma). Consejería de Educación y CulturaMadridMadrid (Comunidad Autónoma). Subdirección General de Formación del Profesorado. CRIF Las Acacias; General Ricardos 179 - 28025 Madrid; Tel. + 34915250893ES

Meteolab as an educational tool for Meteorology in the Classroom

El Presente proyecto es una continuación de proyectos anteriores dentro de la plataforma de divulgación Meteolab. Meteolab es un proyecto de divulgación de Meteorología y Clima que tiene su origen en 2002, cuando se comenzaron a diseñar experimentos de bajo coste con materiales caseros para la Semana de la Ciencia de la Comunidad de Madrid (CAM). Con los años, se generó un conocimiento que se materializó en 2010 con la concesión de un Proyecto de Innovación Educativa (PIE) financiado por la Universidad Complutense de Madrid (UCM), dirigido por Belén Rodríguez de Fonseca. Gracias a este primer proyecto en el que trabajaron muchos profesores y alumnos de ciencias de la atmósfera, se gestó un portal web (meteolab.fis.ucm.es) en el que los experimentos se explicaban y se grababan para impulsar su difusión. Más adelante, en un segundo proyecto de Innovación Educativa, dirigido por la profesora Maria Luisa Montoya, los contenidos fueron traducidos al inglés. En concreto, los experimentos que componen Meteolab tienen como principal objetivo entender los principios y variables que determinan el comportamiento de las masas de aire en la atmósfera y de agua en el océano. La idea consiste en visualizar con experimentos sencillos las leyes físicas que gobiernan la atmósfera y el océano: movimientos horizontales y verticales, cambios de estado, mezcla y equilibrio, así como la interacción entre componentes. Se persigue observar los procesos meteorológicos familiares, como son la formación de una nube, los tornados, la convección, la formación de borrascas o la lluvia, entendiendo los procesos físicos que los producen. Finalmente, Meteolab permite también visualizar fenómenos climáticos como el efecto invernadero, el fenómeno de El Niño, el deshielo del Ártico, la influencia de los volcanes en el clima o la subida del nivel del mar. Existe un catálogo de experimentos, la mayoría de los cuales pueden consultarse a través del portal meteolab.fis.ucm.es, encontrándose todos ellos físicamente localizados en el Laboratorio Elvira Zurita de la Facultad de Ciencias Físicas. Tras la experiencia acumulada durante los 18 años de existencia de Meteolab, en los que se han adecuado las explicaciones de los experimentos a distintos niveles de dificultad (infantil, primaria, secundaria, bachillerato y Universidad de mayores), se ha sugerido la idoneidad de adaptar los contenidos a los estudiantes del Grado en Física y del Máster en Meteorología y Geofísica de la UCM. Así, por ejemplo, cuando se explica la formación de una nube, se puede ir complicando el discurso dependiendo de los diferentes ciclos de la enseñanza. De esta manera, para un nivel de escuela primaria uno sólo tiene que explicar que el aire se enfría al ascender, y al enfriarse se forman gotas de agua que forman las nubes. Al llegar a secundaria, los estudiantes aprenden el concepto de presión atmosférica y la relación entre la temperatura, la presión y el volumen de una parcela de aire. Más adelante, en el Grado en Física, se estudia la tensión de vapor, la expansión adiabática y la existencia de núcleos de condensación. Finalmente, en el Máster en Meteorología se aprenden los distintos procesos de nucleación y tipos de nubes. Todos estos conceptos van complicando la explicación, por lo que un mismo experimento puede explicarse tanto en una escuela infantil como en una Universidad. Es por ello, que, aprovechando la plataforma de divulgación Meteolab, hemos decidido dar un paso adelante y adaptar y ampliar los contenidos de Meteolab, para así poder integrarlos en los currícula del Grado en Física y del Máster en Meteorología y Geofísica de la UCM. Con todo ello, los objetivos del presente proyecto han sido: -Implementar los experimentos de Meteolab en el Aula, tanto en las asignaturas de Grado como en las de Máster. -Adaptar los contenidos existentes del portal web Meteolab (meteolab.fis.ucm.es) a las asignaturas relacionadas con Meteorología del Grado en Física y del Máster en Meteorología y Geofísica, con el fin de visualizar procesos físicos que se explican en el aula. -Añadir a Meteolab nuevos contenidos en relación con la dinámica de la atmósfera y el cambio climático. -Evaluar la mejora de la comprensión por parte del alumnado de los procesos que tienen lugar principalmente en la atmósfera y el océano, y su relación con el clima y su variabilidad.This project is a continuation of previous projects within the Meteolab outreach platform. Meteolab is a Meteorology and Climate outreach project that has its origins in 2002, when low-cost experiments with homemade materials were designed for the Science Week of the Community of Madrid (CAM). Over the years, knowledge was generated and materialized in 2010 with the award of an Educational Innovation Project (PIE) funded by the Complutense University of Madrid (UCM), directed by Belén Rodríguez de Fonseca. Thanks to this first project, in which many teachers and students of atmospheric sciences worked, a web portal was created (meteolab.fis.ucm.es) in which the experiments were explained and recorded to promote their dissemination. Later, in a second Educational Innovation project, directed by Professor Maria Luisa Montoya, the contents were translated into English. Specifically, the main objective of the experiments that make up Meteolab is to understand the principles and variables that determine the behavior of air masses in the atmosphere and water masses in the ocean. The idea is to visualize with simple experiments the physical laws that govern the atmosphere and the ocean: horizontal and vertical movements, state changes, mixing and equilibrium, as well as the interaction between components. The aim is to observe meteorological processes, such as cloud formation, tornadoes, convection, squall formation or rain, understanding the physical processes that produce them. Finally, Meteolab also allows to visualize climatic phenomena such as the greenhouse effect, the El Niño phenomenon, the melting of the Arctic ice, the influence of volcanoes on the climate or the rise in sea level. There is a catalog of experiments, most of which can be consulted through the portal meteolab.fis.ucm.es, all of which are physically located in the Elvira Zurita Laboratory of the Faculty of Physical Sciences. After the experience accumulated during the 18 years of existence of Meteolab, in which the explanations of the experiments have been adapted to different levels of difficulty ( primary, secondary, high school and senior university), it has been suggested the suitability of adapting the contents to the students of the Degree in Physics and the Master in Meteorology and Geophysics of the UCM. Thus, for example, when explaining the formation of a cloud, the discourse can be complicated depending on the different teaching cycles. Thus, for an elementary school level, one only has to explain that the air cools as it rises, and as it cools, water droplets form and form clouds. By high school, students learn the concept of atmospheric pressure and the relationship between temperature, pressure and volume of a parcel of air. Later, in the Bachelor's Degree in Physics, vapor tension, adiabatic expansion and the existence of condensation nuclei are studied. Finally, in the Master's Degree in Meteorology, the different processes of nucleation and types of clouds are learned. All these concepts complicate the explanation, so that the same experiment can be explained both in a kindergarten and in a university. That is why, taking advantage of the Meteolab dissemination platform, we have decided to take a step forward and adapt and expand the contents of Meteolab, in order to integrate them into the curricula of the Degree in Physics and the Master in Meteorology and Geophysics of the UCM. With all this, the objectives of the present project have been: -Implement Meteolab experiments in the classroom, both in undergraduate and master's degree courses. -To adapt the existing contents of the Meteolab web portal (meteolab.fis.ucm.es) to the subjects related to Meteorology of the Degree in Physics and the Master in Meteorology and Geophysics, in order to visualize physical processes that are explained in the classroom. -Add to Meteolab new contents related to atmospheric dynamics and climate change. -To evaluate the improvement of the students' understanding of the processes that take place mainly in the atmosphere and the ocean, and their relationship with climate and its variability.Depto. de Física de la Tierra y AstrofísicaFac. de Ciencias FísicasFALSEsubmitte

Switching TNF antagonists in patients with chronic arthritis: An observational study of 488 patients over a four-year period

The objective of this work is to analyze the survival of infliximab, etanercept and adalimumab in patients who have switched among tumor necrosis factor (TNF) antagonists for the treatment of chronic arthritis. BIOBADASER is a national registry of patients with different forms of chronic arthritis who are treated with biologics. Using this registry, we have analyzed patient switching of TNF antagonists. The cumulative discontinuation rate was calculated using the actuarial method. The log-rank test was used to compare survival curves, and Cox regression models were used to assess independent factors associated with discontinuing medication. Between February 2000 and September 2004, 4,706 patients were registered in BIOBADASER, of whom 68% had rheumatoid arthritis, 11% ankylosing spondylitis, 10% psoriatic arthritis, and 11% other forms of chronic arthritis. One- and two-year drug survival rates of the TNF antagonist were 0.83 and 0.75, respectively. There were 488 patients treated with more than one TNF antagonist. In this situation, survival of the second TNF antagonist decreased to 0.68 and 0.60 at 1 and 2 years, respectively. Survival was better in patients replacing the first TNF antagonist because of adverse events (hazard ratio (HR) for discontinuation 0.55 (95% confidence interval (CI), 0.34-0.84)), and worse in patients older than 60 years (HR 1.10 (95% CI 0.97-2.49)) or who were treated with infliximab (HR 3.22 (95% CI 2.13-4.87)). In summary, in patients who require continuous therapy and have failed to respond to a TNF antagonist, replacement with a different TNF antagonist may be of use under certain situations. This issue will deserve continuous reassessment with the arrival of new medications. © 2006 Gomez-Reino and Loreto Carmona; licensee BioMed Central Ltd