Factors explaining the application of the law of patient autonomy by surgical staff

Objetivos: Explorar qué factores del contexto explican la aplicación de la Ley de autonomía del paciente (LAP) por parte de profesionales implicados en el proceso quirúrgico. Métodos: Estudio descriptivo transversal mediante encuesta en el Hospital Virgen Macarena de Sevilla con personal del área quirúrgica. Variable dependiente: aplicación de la LAP. Variables independientes: percepción de características socioestructurales, según modelo de Kanter, percepción de colaboración interprofesional y conocimiento de la LAP. Se realizó análisis exploratorio, bivariado con pruebas paramétricas y no paramétricas, y regresiones simples y múltiples. El nivel de confianza fue del 95%. Resultados: Participantes: 170 profesionales (tasa de respuesta: 60,28%). Los comportamientos acordes con la LAP se presentan entre un nivel medio y alto, en médicos y enfermeras. Respecto a la aplicación de la LAP según las variables sociolaborales, hay diferencias estadísticamente significativas, por parte del personal médico, en el área de trabajo y en la especialidad. El análisis de regresión múltiple muestra la relación de la aplicación de la LAP con la colaboración interprofesional, en el personal médico. Conclusiones: El modelo de Kanter y la escala de colaboración interprofesional pueden ayudarnos a explicar la influencia del contexto hospitalario en la aplicación de la LAP, y los resultados obtenidos podrían orientar el dise˜no de estrategias dirigidas a la implementación de la ley. Sería necesario superar estructuras tradicionales y generar condiciones descentralizadas y flexibles, que estimulen el trabajo en equipo y la toma de decisiones compartidas.Objective: To examine which contextual factors explain the implementation of the Patient Autonomy Law (LAP) by professionals involved in the surgical process. Methods: A descriptive cross sectional study survey. It was conducted at the Hospital Virgen Macarena in Seville with the surgical staff. Dependent variable: the application of LAP. Independent variables: the perception of socio-structural organizational characteristics according to Kanter’s model (organizational culture, sociopolitical support, access to information, and access to resources), the perception of interprofessional collaboration, and knowledge of the LAP. We performed exploratory analysis, bivariate with parametric and nonparametric tests depending on the nature of the distributions; simple regression to determine the weight of each explanatory variable on the application of the LAP and, multiples introducing in the models those variables that had obtained significant regression coefficients. The analysis performed with a confidence level of 95%. Results: Participants: 170 professionals (response rate: 60.28%). Behaviour according to the LAP is present in a medium-high level among physicians and nurses. Significant differences were observed in the application of the LAP according to the different sociolaboral variables and considering medical staff, the working environment and the specialty. Multiple regression analyses revealed the relationship between the application of the LAP and interprofessional collaboration, in physicians. Conclusions: Kanter’s model and the scale of interprofessional collaboration, may contribute to the explanation of the influence of the hospital context in the implementation of the LAP and the results may guide us when designing strategies to implement the law. It would be necessary to overcome the traditional structures and create decentralized and flexible conditions that encourage teamwork and shared decision making.Consejería de Salud de la Junta de Andalucía CS0117/20

A neurodegenerative disease landscape of rare mutations in Colombia due to founder effects

Background The Colombian population, as well as those in other Latin American regions, arose from a recent tri-continental admixture among Native Americans, Spanish invaders, and enslaved Africans, all of whom passed through a population bottleneck due to widespread infectious diseases that left small isolated local settlements. As a result, the current population reflects multiple founder effects derived from diverse ancestries. Methods We characterized the role of admixture and founder effects on the origination of the mutational landscape that led to neurodegenerative disorders under these historical circumstances. Genomes from 900 Colombian individuals with Alzheimer’s disease (AD) [n = 376], frontotemporal lobar degeneration-motor neuron disease continuum (FTLD-MND) [n = 197], early-onset dementia not otherwise specified (EOD) [n = 73], and healthy participants [n = 254] were analyzed. We examined their global and local ancestry proportions and screened this cohort for deleterious variants in disease-causing and risk-conferring genes. Results We identified 21 pathogenic variants in AD-FTLD related genes, and PSEN1 harbored the majority (11 pathogenic variants). Variants were identified from all three continental ancestries. TREM2 heterozygous and homozygous variants were the most common among AD risk genes (102 carriers), a point of interest because the disease risk conferred by these variants differed according to ancestry. Several gene variants that have a known association with MND in European populations had FTLD phenotypes on a Native American haplotype. Consistent with founder effects, identity by descent among carriers of the same variant was frequent. Conclusions Colombian demography with multiple mini-bottlenecks probably enhanced the detection of founder events and left a proportionally higher frequency of rare variants derived from the ancestral populations. These findings demonstrate the role of genomically defined ancestry in phenotypic disease expression, a phenotypic range of different rare mutations in the same gene, and further emphasize the importance of inclusiveness in genetic studies.Q2Q2Antecedentes La población colombiana, así como la de otras regiones latinoamericanas, surgió de una mezcla tricontinental reciente entre los nativos americanos, los invasores españoles y los africanos esclavizados, todos los cuales pasaron por un cuello de botella poblacional debido a enfermedades infecciosas generalizadas que dejaron a pequeños aislados. asentamientos locales. Como resultado, la población actual refleja múltiples efectos fundadores derivados de diversas ascendencias. Métodos Caracterizamos el papel de la mezcla y los efectos fundadores en el origen del paisaje mutacional que condujo a trastornos neurodegenerativos en estas circunstancias históricas. Genomas de 900 individuos colombianos con enfermedad de Alzheimer (EA) [n = 376], continuo degeneración lobar frontotemporal-enfermedad de la motoneurona (FTLD-MND) [n = 197], demencia de inicio temprano no especificada (EOD) [n = 73 ], y participantes sanos [n = 254] fueron analizados. Examinamos sus proporciones de ascendencia global y local y examinamos esta cohorte en busca de variantes nocivas en los genes que causan enfermedades y confieren riesgos. Resultados Identificamos 21 variantes patogénicas en genes relacionados con AD-FTLD, y PSEN1 albergaba la mayoría (11 variantes patogénicas). Se identificaron variantes de las tres ascendencias continentales. Las variantes heterocigotas y homocigotas de TREM2 fueron las más comunes entre los genes de riesgo de EA (102 portadores), un punto de interés porque el riesgo de enfermedad conferido por estas variantes difería según la ascendencia. Varias variantes genéticas que tienen una asociación conocida con MND en poblaciones europeas tenían fenotipos FTLD en un haplotipo nativo americano. De acuerdo con los efectos del fundador, la identidad por descendencia entre portadores de la misma variante fue frecuente. Conclusiones La demografía colombiana con múltiples mini-cuellos de botella probablemente mejoró la detección de eventos fundadores y dejó una frecuencia proporcionalmente más alta de variantes raras derivadas de las poblaciones ancestrales. Estos hallazgos demuestran el papel de la ascendencia definida genómicamente en la expresión fenotípica de la enfermedad, un rango fenotípico de diferentes mutaciones raras en el mismo gen, y enfatizan aún más la importancia de la inclusión en los estudios genéticos.https://orcid.org/0000-0001-6529-7077https://scholar.google.com/citations?hl=es&user=kaGongoAAAAJ&view_op=list_works&sortby=pubdatehttps://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0000055000&lang=esRevista Internacional - Indexad

A neurodegenerative disease landscape of rare mutations in Colombia due to founder effects.

Background: The Colombian population, as well as those in other Latin American regions, arose from a recent tri-continental admixture among Native Americans, Spanish invaders, and enslaved Africans, all of whom passed through a population bottleneck due to widespread infectious diseases that left small isolated local settlements. As a result, the current population reflects multiple founder effects derived from diverse ancestries. Methods: We characterized the role of admixture and founder effects on the origination of the mutational landscape that led to neurodegenerative disorders under these historical circumstances. Genomes from 900 Colombian individuals with Alzheimer's disease (AD) [n = 376], frontotemporal lobar degeneration-motor neuron disease continuum (FTLD-MND) [n = 197], early-onset dementia not otherwise specified (EOD) [n = 73], and healthy participants [n = 254] were analyzed. We examined their global and local ancestry proportions and screened this cohort for deleterious variants in disease-causing and risk-conferring genes. Results: We identified 21 pathogenic variants in AD-FTLD related genes, and PSEN1 harbored the majority (11 pathogenic variants). Variants were identified from all three continental ancestries. TREM2 heterozygous and homozygous variants were the most common among AD risk genes (102 carriers), a point of interest because the disease risk conferred by these variants differed according to ancestry. Several gene variants that have a known association with MND in European populations had FTLD phenotypes on a Native American haplotype. Consistent with founder effects, identity by descent among carriers of the same variant was frequent. Conclusions: Colombian demography with multiple mini-bottlenecks probably enhanced the detection of founder events and left a proportionally higher frequency of rare variants derived from the ancestral populations. These findings demonstrate the role of genomically defined ancestry in phenotypic disease expression, a phenotypic range of different rare mutations in the same gene, and further emphasize the importance of inclusiveness in genetic studies

Genetic associations with age at dementia onset in the PSEN1 E280A Colombian kindred

INTRODUCTION: Genetic associations with Alzheimer's disease (AD) age at onset (AAO) could reveal genetic variants with therapeutic applications. We present a large Colombian kindred with autosomal dominant AD (ADAD) as a unique opportunity to discover AAO genetic associations. METHODS: A genetic association study was conducted to examine ADAD AAO in 340 individuals with the PSEN1 E280A mutation via TOPMed array imputation. Replication was assessed in two ADAD cohorts, one sporadic early-onset AD study and four late-onset AD studies. RESULTS: 13 variants had p<1x10(-7) or p<1x10(-5) with replication including three independent loci with candidate associations with clusterin including near CLU. Other suggestive associations were identified in or near HS3ST1, HSPG2, ACE, LRP1B, TSPAN10, and TSPAN14. DISCUSSION: Variants with suggestive associations with AAO were associated with biological processes including clusterin, heparin sulfate, and amyloid processing. The detection of these effects in the presence of a strong mutation for ADAD reinforces their potentially impactful role