Una comparación de pruebas de igualdad de dos riesgos competitivos

Los estudios de confiabilidad y supervivencia buscan analizar por medio de un conjunto de técnicas la variable “tiempo hasta que ocurre un evento”, tales como el tiempo hasta la muerte o curación, la probabilidad de falla en cada instante de tiempo, el riesgo de falla, etc. El análisis de los modelos de riesgos competitivos es apropiado para estudiar el comportamiento de una unidad o sujeto que puede fallar por diferentes causas, donde se observa tanto el tiempo hasta la falla, como el tipo de falla. En este trabajo se abord´o la problem´atica de dos riesgos que están compitiendo para causar la falla de un sujeto; en particular determinar si los riesgos o probabilidad de falla asociada a cada tipo de falla son igualmente importantes o si un riesgo es más serio que el otro. Para este fin se hizo un estudio de la prueba de hipótesis para la igualdad de las dos funciones de incidencia acumulada asociadas a los riesgos. Se realizó un estudio de simulación donde se comparan algunos de los procedimientos de prueba que han sido propuestos para este fin; y así, poder determinar el comportamiento de estos procedimientos de prueba bajo varios escenarios que permitan evaluar el desempe˜no de los mismos. Se incluyen los procedimientos de prueba usando datos reales de pacientes con linfoma.Abstract: In survival and reliability studies the analysis is intended by means of a set of variable techniques studying “time until an event occurs”, for example, the time to death or cure, the probability of failure at each instant, risk of failure, etc. The analysis of competing risk models is appropriate to study the behavior of a unit that can fail for different causes, where the time and time to failure are observed. In this paper, it is tackled the problematic of the risks that are competing to cause the failure from the subject; in particular whether the risks or likelihood of failure associated with each type of failure are equally important or whether a risk is more serious than the other. For this purpose will be made a study of hypothesis tests for equality of cumulative incidence functions of associated with risks. A comparative study of some of the test procedures that have been proposed for this purpose, and thus able to determine the behavior of the different tests in various scenarios to evaluate the performance of the same will be made.Test procedures are included using real data of patients with lymphoma.Maestrí

A comparison test of equality of two competing risks

1 recurso en línea (páginas 97-111).En este artículo se abordó la problemática de dos riesgos que están compitiendo para causar la falla de un sujeto; en particular determinar si los riesgos o probabilidad de falla asociada a cada tipo de falla son igualmente importantes o si un riesgo es más serio que el otro. Para este fin se hizo un estudio de la prueba de hipótesis para la igualdad de las dos funciones de incidencia acumulada asociadas a los riesgos. Se realizó un estudio de simulación donde se comparan algunos de los procedimientos de prueba que han sido propuestos para este fin; y así, poder determinar el comportamiento de estos procedimientos de prueba bajo varios escenarios que permitan evaluar el desempeño de los mismos. Se incluye una aplicación de los procedimientos de prueba usando datos reales de pacientes con linfoma.In this paper, it is tackled the problematic of the risks that are competing to cause the failure from the subject; in particular whether the risks or likelihood of failure associated with each type of failure are equally important or whether a risk is more serious than the other. For this purpose will be made a study of hypothesis tests for equality of cumulative incidence functions of associated with risks. A comparative study of some of the test procedures that have been proposed for this purpose, and thus able to determine the behavior of the different tests in various scenarios to evaluate the performance of the same will be made. Test procedures are included using real data of patients with lymphoma.Bibliografía: páginas 110-111

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health (FIS; PI16/00425 and PI19/00321), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER, 06/07/0036), IIS-FJD BioBank (PT13/0010/0012), Comunidad de Madrid (CAM, RAREGenomics Project, B2017/BMD-3721), European Regional Development Fund (FEDER), the Organización Nacional de Ciegos Españoles (ONCE), Fundación Ramón Areces, Fundación Conchita Rábago and the University Chair UAM-IIS-FJD of Genomic Medicine. Irene Perea-Romero is supported by a PhD fellowship from the predoctoral Program from ISCIII (FI17/00192). Ionut F. Iancu is supported by a grant from the Comunidad de Madrid (CAM, PEJ-2017-AI/BMD7256). Marta del Pozo-Valero is supported by a PhD grant from the Fundación Conchita Rábago. Berta Almoguera is supported by a Juan Rodes program from ISCIII (JR17/00020). Pablo Minguez is supported by a Miguel Servet program from ISCIII (CP16/00116). Marta Corton is supported by a Miguel Servet program from ISCIII (CPII17/00006). The funders played no role in study design, data collection, data analysis, manuscript preparation and/or publication decisions

Soy Niña

Este libro pretende contribuir al reencuentro de la educación con esas finalidades que verdaderamente importan a una niña o un niño: ser feliz, jugar, vivir juntos y (no) aprender. Para ello hemos puesto el arte, nuestras experiencias y el saber acumulado al servicio del disfrute, el cuestionamiento, el análisis crítico y la construcción común de un presente deseable. Un texto colaborativo coordinado por Ignacio Calderón Almendros y realizado por alumnado de Educación y Cambio Social en el Grado en Educación Infantil de la Universidad de Málaga

Guía para el gerenciamiento de proyectos y programas escolares

Ubicación en Biblioteca USB Medellín (San Benito): CD-2672tLa Gerencia de Proyectos se constituye en una necesidad apremiante en el sector educativo, cuando de hacer Gerencia efectiva se trata. Todo el tiempo diseñamos e implementamos proyectos y programas escolares. Si lo hacemos desde una perspectiva gerencial, estamos seguros de que la productividad de la Organización escolar, no se hará esperar; en el presente trabajo se propone una guía para el gerenciamiento de proyectos y programas escolares, la cual servirá para que los agentes educativos se concienticen de realizar su función misional tratando de lograr efectividad con el manejo de los recursos y el mejoramiento de la calidad de la educación

Evolution over Time of Ventilatory Management and Outcome of Patients with Neurologic Disease∗

OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p < 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p < 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p < 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old