RESUMEN
NOTCH4 has long been identified as a candidate susceptibility gene for schizophrenia, but the collective body of genetic association studies of this gene has been less than conclusive. Recently a variant in NOTCH4 was implicated as one of the most reliably associated polymorphisms observed in a genome-wide association scan of the disorder, and the collective evidence for this polymorphism now surpasses criteria for genome-wide significance. To place these developments in context, we now summarize the initial work identifying NOTCH4 as a candidate gene for schizophrenia. The results of the genome-wide association studies that have confirmed this as a risk gene, and novel bioinformatics analyses that reveal potential functional profiles of the most likely risk-conferring polymorphisms. These analyses suggest that the NOTCH4 polymorphisms most strongly associated with schizophrenia exert their effects on susceptibility by altering the efficiency and/or alternative splicing of Notch4 transcripts. Further experimental evidence should be pursued to clarify the NOTCH4-regulated molecular and cellular phenotypes of relevance to the disorder, and the functional consequences of the implicated polymorphisms in the gene.
Asunto(s)
Estudios de Asociación Genética , Sitios Genéticos/genética , Predisposición Genética a la Enfermedad , Proteínas Proto-Oncogénicas/genética , Receptores Notch/genética , Esquizofrenia/genética , Humanos , Polimorfismo de Nucleótido Simple/genética , Receptor Notch4RESUMEN
BACKGROUND: Providing adequate psychiatry consultation capacity on a 24/7 basis is an intrinsic challenge throughout many multihospital health care systems. At present, implementation research has not adequately defined the effectiveness and feasibility of a centralized telepsychiatry consultation service within a multihospital health care system. OBJECTIVE: To demonstrate feasibility of a hub and spoke model for provision of inpatient consult telepsychiatry service from an academic medical center to 2 affiliated regional hospital sites, to reduce patient wait time, and to develop best practice guidelines for telepsychiatry consultations to the acutely medically ill. METHODS: The implementation, interprofessional workflow, process of triage, and provider satisfaction were described from the first 13 months of the service. RESULTS: This pilot study resulted in 557 completed telepsychiatry consults over the course of 13 months from 2018 to 2019. A range of psychiatric conditions commonly encountered by consultation-liaison services were diagnosed and treated through the teleconferencing modality. The most common barriers to successful use of telepsychiatry were defined for the 20% of consult requests that were retriaged to face-to-face evaluation. The average patient wait time from consult request to initial consultation was reduced from >24 hours to 92 minutes. CONCLUSIONS: This study demonstrated the feasibility of a centralized telepsychiatry hub to improve delivery of psychiatry consultation within a multihospital system with an overall reduction in patient wait time. This work may serve as a model for further design innovation across many health care settings and new patient subpopulations.