Un examen actualizado de la percepción de las barreras para la implementación de la farmacogenómica y la utilidad de los pares fármaco/gen en América Latina y el Caribe

La farmacogenómica (PGx) se considera un campo emergente en los países en desarrollo. La investigación sobre PGx en la región de América Latina y el Caribe (ALC) sigue siendo escasa, con información limitada en algunas poblaciones. Por lo tanto, las extrapolaciones son complicadas, especialmente en poblaciones mixtas. En este trabajo, revisamos y analizamos el conocimiento farmacogenómico entre la comunidad científica y clínica de ALC y examinamos las barreras para la aplicación clínica. Realizamos una búsqueda de publicaciones y ensayos clínicos en este campo en todo el mundo y evaluamos la contribución de ALC. A continuación, realizamos una encuesta regional estructurada que evaluó una lista de 14 barreras potenciales para la aplicación clínica de biomarcadores en función de su importancia. Además, se analizó una lista emparejada de 54 genes/fármacos para determinar una asociación entre los biomarcadores y la respuesta a la medicina genómica. Esta encuesta se comparó con una encuesta anterior realizada en 2014 para evaluar el progreso en la región. Los resultados de la búsqueda indicaron que los países de América Latina y el Caribe han contribuido con el 3,44% del total de publicaciones y el 2,45% de los ensayos clínicos relacionados con PGx en todo el mundo hasta el momento. Un total de 106 profesionales de 17 países respondieron a la encuesta. Se identificaron seis grandes grupos de obstáculos. A pesar de los continuos esfuerzos de la región en la última década, la principal barrera para la implementación de PGx en ALC sigue siendo la misma, la "necesidad de directrices, procesos y protocolos para la aplicación clínica de la farmacogenética/farmacogenómica". Las cuestiones de coste-eficacia se consideran factores críticos en la región. Los puntos relacionados con la reticencia de los clínicos son actualmente menos relevantes. Según los resultados de la encuesta, los pares gen/fármaco mejor clasificados (96%-99%) y percibidos como importantes fueron CYP2D6/tamoxifeno, CYP3A5/tacrolimus, CYP2D6/opioides, DPYD/fluoropirimidinas, TMPT/tiopurinas, CYP2D6/antidepresivos tricíclicos, CYP2C19/antidepresivos tricíclicos, NUDT15/tiopurinas, CYP2B6/efavirenz y CYP2C19/clopidogrel. En conclusión, aunque la contribución global de los países de ALC sigue siendo baja en el campo del PGx, se ha observado una mejora relevante en la región. La percepción de la utilidad de las pruebas PGx en la comunidad biomédica ha cambiado drásticamente, aumentando la concienciación entre los médicos, lo que sugiere un futuro prometedor en las aplicaciones clínicas de PGx en ALC.Pharmacogenomics (PGx) is considered an emergent field in developing countries. Research on PGx in the Latin American and the Caribbean (LAC) region remains scarce, with limited information in some populations. Thus, extrapolations are complicated, especially in mixed populations. In this paper, we reviewed and analyzed pharmacogenomic knowledge among the LAC scientific and clinical community and examined barriers to clinical application. We performed a search for publications and clinical trials in the field worldwide and evaluated the contribution of LAC. Next, we conducted a regional structured survey that evaluated a list of 14 potential barriers to the clinical implementation of biomarkers based on their importance. In addition, a paired list of 54 genes/drugs was analyzed to determine an association between biomarkers and response to genomic medicine. This survey was compared to a previous survey performed in 2014 to assess progress in the region. The search results indicated that Latin American and Caribbean countries have contributed 3.44% of the total publications and 2.45% of the PGx-related clinical trials worldwide thus far. A total of 106 professionals from 17 countries answered the survey. Six major groups of barriers were identified. Despite the region’s continuous efforts in the last decade, the primary barrier to PGx implementation in LAC remains the same, the “need for guidelines, processes, and protocols for the clinical application of pharmacogenetics/pharmacogenomics”. Cost-effectiveness issues are considered critical factors in the region. Items related to the reluctance of clinicians are currently less relevant. Based on the survey results, the highest ranked (96%–99%) gene/drug pairs perceived as important were CYP2D6/tamoxifen, CYP3A5/tacrolimus, CYP2D6/opioids, DPYD/fluoropyrimidines, TMPT/thiopurines, CYP2D6/tricyclic antidepressants, CYP2C19/tricyclic antidepressants, NUDT15/thiopurines, CYP2B6/efavirenz, and CYP2C19/clopidogrel. In conclusion, although the global contribution of LAC countries remains low in the PGx field, a relevant improvement has been observed in the region. The perception of the usefulness of PGx tests in biomedical community has drastically changed, raising awareness among physicians, which suggests a promising future in the clinical applications of PGx in LAC

Ecological vulnerability of the chondrichthyan fauna of southern Australia to the stressors of climate change, fishing and other anthropogenic hazards

We develop a potentially widely applicable framework for analysing the vulnerability, resilience risk and exposure of chondrichthyan species to all types of anthropogenic stressors in the marine environment. The approach combines the three components of widely applied vulnerability analysis (exposure, sensitivity and adaptability) (ESA) with three components (exposure, susceptibility and productivity) (ESP) of our adaptation of productivity–susceptibility analysis (PSA). We apply our 12-step ESA‒ESP analysis to evaluate the vulnerability (risk of a marked reduction of the population) of each of 132 chondrichthyan species in the Exclusive Economic Zone of southern Australia. The vul nerability relates to a species’ resilience to a spatial (or suitability) reduction of its habitats from exposure to up to eight climate change stressors. Vulnerability also relates to anthro pogenic mortality added to natural mortality from exposure to the stressors of five types of fishing and seven other types of anthropogenic hazards. We use biological attributes as risk factors to evaluate risk related to resilience at the species or higher taxonomic level. We evaluate each species’ exposure to anthropogenic stressors by assigning it to one of six ecological groups based on its lifestyle (demersal versus pelagic) and habitat, defined by bathymetric range and substrates. We evaluate vulnerability for 11 scenarios: 2000– 2006 when fishing effort peaked; 2018 following a decade of fisheries management reforms; low, medium and high standard future carbon dioxide equivalent emissions sce narios; and their six possible climate–fishing combinations. Our results demonstrate the value of refugia from fishing and how climate change exacerbates the risks from fishing.Fil: Walker, Terence I.. Monash University; Australia. The University of Melbourne; AustraliaFil: Day, Robert W.. The University of Melbourne; AustraliaFil: Awruch, Cynthia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Tasmania; AustraliaFil: Bell, Justin D.. Institute For Marine And Antarctic Studies; AustraliaFil: Braccini, Juan Matias. Wa Fisheries And Marine Research Laboratories; AustraliaFil: Dapp, Derek R.. Monash University; AustraliaFil: Finotto, Licia. Monash University; AustraliaFil: Frick, Lorenz H.. Monash University; AustraliaFil: Garcés-García, Karla C.. Universidad Veracruzana; México. The University of Melbourne; AustraliaFil: Guida, Leonardo. Monash University; AustraliaFil: Huveneers, Charlie. Flinders University; AustraliaFil: Martins, Camila L.. Monash University; AustraliaFil: Rochowski, Bastien E.A.. The University of Melbourne; AustraliaFil: Tovar-Ávila, Javier. Inapesca; MéxicoFil: Trinnie, Fabian I.. Wa Fisheries And Marine Research Laboratories; AustraliaFil: Reina, Richard D.. Monash University; Australi