Asunto(s)
Sulfato de Atazanavir/farmacocinética , Infecciones por VIH/genética , Inhibidores de la Proteasa del VIH/farmacocinética , Farmacogenética/métodos , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Sulfato de Atazanavir/uso terapéutico , Sinergismo Farmacológico , Glucuronosiltransferasa/genética , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Transportador 1 de Anión Orgánico Específico del Hígado/genética , Receptor X de Pregnano/genética , Ritonavir/farmacocinética , Ritonavir/uso terapéuticoRESUMEN
Since the first sequencing of the human genome, associated sequencing costs have dramatically lowered, leading to an explosion of genomic data. This valuable data should in theory be of huge benefit to the global community, although unfortunately the benefits of these advances have not been widely distributed. Much of today's clinical-genomic data is siloed and inaccessible in adherence with strict governance and privacy policies, with more than 97% of hospital data going unused, according to one reference. Despite these challenges, there are promising efforts to make clinical-genomic data accessible and useful without compromising security. Specifically, federated data platforms are emerging as key resources to facilitate secure data sharing without having to physically move the data from outside of its organizational or jurisdictional boundaries. In this perspective, we summarize the overarching progress in establishing federated data platforms, and highlight critical considerations on how they should be managed to ensure patient and public trust. These platforms are enabling global collaboration and improving representation of underrepresented groups, since sequencing efforts have not prioritized diverse population representation until recently. Federated data platforms, when combined with advances in no-code technology, can be accessible to the diverse end-users that make up the genomics workforce, and we discuss potential strategies to develop sustainable business models so that the platforms can continue to enable research long term. Although these platforms must be carefully managed to ensure appropriate and ethical use, they are democratizing access and insights to clinical-genomic data that will progress research and enable impactful therapeutic findings.
Asunto(s)
Hipertermia Maligna/genética , Músculo Esquelético/metabolismo , Canal Liberador de Calcio Receptor de Rianodina/genética , Predisposición Genética a la Enfermedad , Variación Genética , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Hipertermia Maligna/epidemiología , Enfermedades Musculares/inducido químicamente , Enfermedades Musculares/genética , Farmacogenética , Canal Liberador de Calcio Receptor de Rianodina/metabolismoAsunto(s)
Fármacos Anti-VIH/farmacocinética , Benzoxazinas/farmacocinética , Inhibidores de la Transcriptasa Inversa/farmacocinética , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Alquinos , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/efectos adversos , Benzoxazinas/administración & dosificación , Benzoxazinas/efectos adversos , Ciclopropanos , Citocromo P-450 CYP2A6/genética , Citocromo P-450 CYP2A6/metabolismo , Citocromo P-450 CYP2B6/genética , Citocromo P-450 CYP2B6/metabolismo , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Interacciones Farmacológicas , Glucuronosiltransferasa/genética , Glucuronosiltransferasa/metabolismo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , Infecciones por VIH/metabolismo , VIH-1 , Humanos , Redes y Vías Metabólicas , Polimorfismo de Nucleótido Simple , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Inhibidores de la Transcriptasa Inversa/efectos adversosAsunto(s)
Fármacos Neuromusculares Despolarizantes/farmacocinética , Succinilcolina/farmacocinética , Apnea/inducido químicamente , Apnea/genética , Butirilcolinesterasa/deficiencia , Butirilcolinesterasa/genética , Canales de Calcio/genética , Canales de Calcio Tipo L , Humanos , Hiperpotasemia/inducido químicamente , Hiperpotasemia/genética , Hipertermia Maligna/etiología , Hipertermia Maligna/genética , Errores Innatos del Metabolismo/inducido químicamente , Errores Innatos del Metabolismo/genética , Fármacos Neuromusculares Despolarizantes/efectos adversos , Fármacos Neuromusculares Despolarizantes/farmacología , Farmacogenética , Polimorfismo de Nucleótido Simple/genética , Canal Liberador de Calcio Receptor de Rianodina/genética , Succinilcolina/efectos adversos , Succinilcolina/farmacologíaRESUMEN
The identification in a patient of 1 of the 50 variants in the RYR1 or CACNA1S genes reviewed here should lead to a presumption of malignant hyperthermia susceptibility (MHS). MHS can lead to life-threatening reactions to potent volatile anesthetic agents or succinylcholine. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for the use of these agents in patients with these RYR1 or CACNA1S variants (updates at https://cpicpgx.org/guidelines and www.pharmgkb.org).