Comparación de curvas de supervivencia con datos censurados

El análisis de supervivencia es una rama de la Estadística que tiene como objetivo analizar o modelizar el tiempo que tarda en ocurrir uno o más eventos de interés como la muerte de un paciente con cáncer o los fallos en los motores de unas máquinas de una industria textil. Para conseguir dicho objetivo, existe una extensa gama de herramientas entre las que se encuentra la comparación de curvas de supervivencia. El propósito de este trabajo es describir la teoría y la metodología de diversas técnicas de comparación de curvas de supervivencia con datos censurados. Además, con objeto de ilustrar la utilidad de estas técnicas se usarán librerías de R que contienen funciones que llevan a cabo dichas técnicas y se aplicarán sobre datos reales. Palabras clave: análisis de supervivencia, datos censurados por intervalos, datos censurados a la derecha, función de supervivencia, prueba de tendencia, test log-rank ponderado, test de permutación, procesos de conteo.Survival analysis is a branch of Statistics that aims to analyse or model the time it takes for one or more events of interest to occur, such as the death of a cancer patient or the failure of machine motors in a textile industry. In order to achieve this goal, a wide range of tools are available, including the comparison of survival curves. The purpose of this dissertation is to describe the theory and methodology of tests for comparing survival curves with censored data. Furthermore, in order to illustrate the usefulness of these techniques, R libraries containing functions that perform these techniques will be used and applied on real data.Universidad de Sevilla. Doble Grado en Matemáticas y Estadístic

Proanthocyanidins Maintain Cardiac Ionic Homeostasis in Aldosterone-Induced Hypertension and Heart Failure

Excess aldosterone promotes pathological remodeling of the heart and imbalance in cardiac ion homeostasis of sodium, potassium and calcium. Novel treatment with proanthocyanidins in aldosterone-treated rats has resulted in downregulation of cardiac SGK1, the main genomic aldosterone-induced intracellular mediator of ion handling. It therefore follows that proanthocyanidins could be modulating cardiac ion homeostasis in aldosterone-treated rats. Male Wistar rats received aldosterone (1 mg kg−1 day−1) +1% NaCl for three weeks. Half of the animals in each group were simultaneously treated with the proanthocyanidins-rich extract (80% w/w) (PRO80, 5 mg kg−1 day−1). PRO80 prevented cardiac hypertrophy and decreased calcium content. Expression of ion channels (ROMK, NHE1, NKA and NCX1) and calcium transient mediators (CAV1.2, pCaMKII and oxCaMKII) were reduced by PRO80 treatment in aldosterone-treated rats. To conclude, our data indicate that PRO80 may offer an alternative treatment to conventional MR-blockade in the prevention of aldosterone-induced cardiac pathology

A Murine Model of falciparum-Malaria by In Vivo Selection of Competent Strains in Non-Myelodepleted Mice Engrafted with Human Erythrocytes

To counter the global threat caused by Plasmodium falciparum malaria, new drugs and vaccines are urgently needed. However, there are no practical animal models because P. falciparum infects human erythrocytes almost exclusively. Here we describe a reliable falciparum murine model of malaria by generating strains of P. falciparum in vivo that can infect immunodeficient mice engrafted with human erythrocytes. We infected NODscid/β2m−/− mice engrafted with human erythrocytes with P. falciparum obtained from in vitro cultures. After apparent clearance, we obtained isolates of P. falciparum able to grow in peripheral blood of engrafted NODscid/β2m−/− mice. Of the isolates obtained, we expanded in vivo and established the isolate Pf3D70087/N9 as a reference strain for model development. Pf3D70087/N9 caused productive persistent infections in 100% of engrafted mice infected intravenously. The infection caused a relative anemia due to selective elimination of human erythrocytes by a mechanism dependent on parasite density in peripheral blood. Using this model, we implemented and validated a reproducible assay of antimalarial activity useful for drug discovery. Thus, our results demonstrate that P. falciparum contains clones able to grow reproducibly in mice engrafted with human erythrocytes without the use of myeloablative methods

Importance of Timely Treatment Initiation in Infantile-Onset Pompe Disease, a Single-Centre Experience

Abstract Classic infantile Pompe disease (IPD) is a rare lysosomal storage disorder characterized by severe hypertrophic cardiomyopathy and profound muscle weakness. Without treatment, death occurs within the first 2 years of life. Although enzyme replacement therapy (ERT) with alglucosidase alfa has improved survival, treatment outcome is not good in many cases and is largely dependent on age at initiation. The objective of the study was (a) to analyse the different stages in the diagnosis and specific treatment initiation procedure in IPD patients, and (b) to compare clinical and biochemical outcomes depending on age at ERT initiation (<1 month of age vs. <3 months of age). Here, we show satisfactory clinical and biochemical outcomes in two IPD patients after early treatment initiation before 3 months of life with immunomodulatory therapy in the ERT-naïve setting, with a high ERT dose from the beginning. Despite the overall good evolution, the patient who initiated treatment <1 month of life presented even better outcomes than the patient who started treatment <3 months of life, with an earlier normalization of hypertrophic cardiomyopathy, along with CK normalization, highlighting the importance of early treatment initiation in this progressive disease before irreversible muscle damage has occurred.This work was partially funded by the Basque Department of Education (IT1281-19)

Instagram y gamificación para incorporar los procesos fisiológicos al día a día de los estudiantes de Fisiología

El presente proyecto de innovación docente se basa en la utilización de la red social Instagram para incentivar el estudio diario y el aprendizaje cooperativo de una forma lúdica, autónoma y divertida. Se aplicó en la docencia de la Fisiología Humana en distintos grados en los que participa el Departamento de Fisiología. La metodología consiste en que los alumnos, trabajando en grupo, publiquen contenidos en Instagram, para repasar, sintetizar y compartir información de la asignatura. Los objetivos alcanzados fueron: motivación en el estudio continuado, implicación en el proceso de aprendizaje, trabajo en equipo y adquisición de competencias transversales como creatividad, liderazgo y compromiso. La participación en el proyecto fue muy alta (94%), así como la satisfacción de los alumnos, sobre todo en aspectos motivacionales (interés y curiosidad por la asignatura) y de integración, gracias al trabajo en equipo. En conclusión, la red Instagram es una herramienta útil como complemento de las clases, con objeto de incentivar el estudio diario, sintetizar la información y transmitirla mediante trabajo cooperativo

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

A murine model of falciparum-malaria by in vivo selection of competent strains in non-myelodepleted mice engrafted with human erythrocytes.

To counter the global threat caused by Plasmodium falciparum malaria, new drugs and vaccines are urgently needed. However, there are no practical animal models because P. falciparum infects human erythrocytes almost exclusively. Here we describe a reliable falciparum murine model of malaria by generating strains of P. falciparum in vivo that can infect immunodeficient mice engrafted with human erythrocytes. We infected NOD(scid/beta2m-/-) mice engrafted with human erythrocytes with P. falciparum obtained from in vitro cultures. After apparent clearance, we obtained isolates of P. falciparum able to grow in peripheral blood of engrafted NOD(scid/beta2m-/-) mice. Of the isolates obtained, we expanded in vivo and established the isolate Pf3D7(0087/N9) as a reference strain for model development. Pf3D7(0087/N9) caused productive persistent infections in 100% of engrafted mice infected intravenously. The infection caused a relative anemia due to selective elimination of human erythrocytes by a mechanism dependent on parasite density in peripheral blood. Using this model, we implemented and validated a reproducible assay of antimalarial activity useful for drug discovery. Thus, our results demonstrate that P. falciparum contains clones able to grow reproducibly in mice engrafted with human erythrocytes without the use of myeloablative methods

Proyecto de mejora del estilo cognitivo

Trata el desarrollo de habilidades que ayuden al alumnado a mejorar su rendimiento a través de ejercicios que potencian la habilidad cognitiva. Pretende fomentar la reflexión e investigación individual y colectiva del profesorado en el aula, modificar en el alumnado el estilo cognitivo impulsivo haciéndoles más reflexivos e influir en la dinámica del aula fomentando las interacciones del alumnado-profesorado. La dinámica de trabajo tiene cuatro fases: identificar el problema y toma de conciencia de lo que exige, centrar la atención en la respuesta que se da a esa pregunta autoformulada, eliminar las alternativas no válidas hasta encontrar la correcta y autoevaluarse y autoesforzarse. Evalua el grado de consecución de los objetivos a partir de la observación y fichas de control.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

Therapeutic efficacy of diamidine derivatives against <i>P. berghei</i>, <i>P. vinckei</i> and <i>P. falciparum</i>.

<p>(A, B, C) Therapeutic efficacy of pentamidine (40 mg·Kg⁻¹, u.i.d., s.c.), DB75 (10 mg·Kg⁻¹, u.i.d., s.c.) or DB289 (100 mg·Kg^-1, u.i.d., p.o.) against <i>P. berghei</i>, <i>P. vinckei</i> and <i>P. falciparum</i>, respectively. We started treatment when parasitemias where comparable and administered compounds for 4 days. (D, E) Giemsa-stained blood smears from mice infected with <i>P. berghei</i> obtained 48 h after starting treatment with vehicle or DB75 at 10 mg·Kg⁻¹, respectively (×1000 magnification). Neither relevant cellular damage nor significant inhibition of parasitemia were observed at the time of sampling. (F, G) Giemsa-stained blood smears from mice infected with <i>P. vinckei</i> obtained 48 h after starting treatment with vehicle or DB75 at 10 mg·Kg⁻¹, respectively (×1000 magnification). Parasites from treated mice were mostly abnormal late trophozoites. (H, I) Giemsa-stained blood smears from mice infected with <i>P. falciparum</i> obtained 48 h after starting treatment with vehicle or DB75 at 10 mg·Kg⁻¹, respectively (×1000 magnification). Parasites from treated mice were mostly abnormal late trophozoites.</p