Biomarkers Associated with Regorafenib First-Line Treatment Benefits in Metastatic Colorectal Cancer Patients: REFRAME Molecular Study.

First-line treatment with regorafenib in frail metastatic colorectal cancer (mCRC) patients has shown some benefit. To accurately identify such patients before treatment, we studied blood biomarkers and primary tumor molecules. We unveiled serum microRNAs (miRNAs), single-nucleotide polymorphisms (SNPs) in angiogenic-related genes, and Notch 1 expression as biomarkers associated with response or toxicity. MicroRNA array profiling and genotyping of selected SNPs were performed in the blood of fragile mCRC patients treated with regorafenib. Notch 1 and CRC-associated miRNA expression was also analyzed in tumors. High levels of miR-185-5p in serum, rs7993418 in the vascular endothelial growth factor receptor 1 (VEGFR1) gene, and Notch 1 expression in biopsies were associated with a favorable response to treatment. Serum levels of miR-126-3p and miR-152-3p and tumor expression of miR-92a-1-5p were associated with treatment toxicity, particularly interesting in patients exhibiting comorbidities, and high levels of miR-362-3p were associated with asthenia. Additionally, several miRNAs were associated with the presence of metastasis, local recurrence, and peritoneal metastasis. Besides, miRNAs determined in primary tumors were associated with tumor-node-metastasis (TNM) staging. The rs2305948 and rs699947 SNPs in VEGFR2 and VEGFA, respectively, were markers of poor prognosis correlating with locoregional relapse, a higher N stage, and metastatic shedding. In conclusion, VEGF and VEGFR SNPs, miRNAs, and Notch 1 levels are potential useful biomarkers for the management of advanced CRC under regorafenib treatment.

[Usefulness of failure mode and effects analysis to improve patient safety during the process of incorporating new nurses in an intensive care unit]. / Utilidad del análisis modal de fallos y efectos para la mejora de la seguridad de los pacientes, en el proceso de incorporación de nuevo personal de enfermería a un servicio de medicina intensiva.

OBJECTIVE: To analyze proactively the process of incorporating new nurses in the intensive care unit (ICU) in order to detect risk areas and establish improvements that increase critical patient safety. MATERIAL AND METHODS: Once the risk area was defined, the different phases of failure mode and effects analysis (FMEA) were applied: work team selection; process design; process phases definition; failure modes, possible causes and effects analysis; risk priority for each failure, and development of ameliorating and corrective actions. The proposed actions consisted of an orientation and training program (theoretical and practical) for new nurses, a supervision plan, a progressive responsibility program and ICU participation in personnel recruitment. RESULTS: Twelve nurses began to work in the ICU during the first 18 months of the program's implementation. Of these, only one nurse had full experience in critical care and three had partial experience. Participation of the ICU in personnel recruitment was nil. All the nurses with no or partial experience followed the orientation program (nursing supervisor interview, test of previous knowledge, handing over of the employee handbook, etc.), the theoretical and practical training program (supervision and tutorship) and the progressive responsibility program. More than half (63.6%) of the new nurses had another nurse duplicating their jobs during the training period and 54.5% of the new nurses attended the critical care course for nurses. Nurses participating in the orientation and training program expressed a high level of satisfaction. These measures helped nurses to decrease their stress and anxiety, increase and consolidate their knowledge, and provide safer care to critical patients. CONCLUSIONS: FMEA is a useful tool for improving ICU processes, even those involving human resources. The improvements implemented to decrease clinical risk related to the incorporation of new nurses in the ICU, based on previous training, will increase the safety of critical patient care by decreasing human errors due to inexperience.

Utilidad del análisis modal de fallos y efectos para la mejora de la seguridad de los pacientes, en el proceso de incorporación de nuevo personal de enfermería a un servicio de medicina intensiva / Usefulness of failure mode and effects analysis to improve patient safety during the process of incorporating new nurses in an intensive care unit

Objetivo: Analizar proactivamente el proceso de incorporación laboral del personal de enfermería a un servicio de medicina intensiva (SMI) para detectar áreas de riesgo y establecer acciones de mejora que aumenten la seguridad de los pacientes críticos. Material y métodos: Tras detectar el área de riesgo, se aplicó la metodología AMFE en sus diferentes fases: selección del grupo de trabajo, diseño del proceso, identificación de las fases, análisis de fallos, posibles causas y efectos, priorización del riesgo de cada fallo y desarrollo de las acciones de prevención y mejora. Las acciones propuestas fueron: plan de acogida y formación (teórico-práctica), tutela y supervisión, plan de responsabilidad progresiva (PRP) y participación del SMI en la selección del personal. Resultados: Se incorporaron 12 enfermeras en los primeros 18 meses de funcionamiento del plan; de ellas, sólo 1 tenía experiencia plena en UCI y 3, experiencia parcial. La participación del SMI en la selección de personal fue nula. El 100% de las enfermeras sin experiencia o con experiencia parcial siguieron el plan de acogida (entrevista con la supervisora, evaluación de conocimientos previos, entrega del Manual de Acogida), el plan de formación teórico-práctico (tutela y supervisión) y el PRP. El 63,6% de las incorporaciones tuvo “doblaje” de su puesto durante su incorporación. El 54,5% asistió al Curso de Cuidados Críticos para enfermería. Las enfermeras que recibieron el plan de acogida manifiestan un alto grado de satisfacción, y estas medidas contribuyeron a disminuir su estrés y su ansiedad, ampliar y afianzar conocimientos y practicar una asistencia más segura a los pacientes críticos. Conclusiones: El AMFE es una herramienta útil en la mejora de los procesos de los SMI que se puede aplicar también a aquellos en los que están implicados los recursos humanos. Las mejoras implantadas para disminuir el riesgo asistencial en relación con la incorporación laboral de nuevas enfermeras, basadas en la formación previa, contribuirán a dar una asistencia más segura a los enfermos, al disminuir los errores humanos derivados de la inexperiencia (AU)

Objective: To analyze proactively the process of incorporating new nurses in the intensive care unit (ICU) in order to detect risk areas and establish improvements that increase critical patient safety. Material and methods: Once the risk area was defined, the different phases of failure mode and effects analysis (FMEA) were applied: work team selection; process design; process phases definition; failure modes, possible causes and effects analysis; risk priority for each failure, and development of ameliorating and corrective actions. The proposed actions consisted of an orientation and training program (theoretical and practical ) for new nurses, a supervision plan, a progressive responsibility program and ICU participation in personnel recruitment. Results: Twelve nurses began to work in the ICU during the first 18 months of the program’s implementation. Of these, only one nurse had full experience in critical care and three had partial experience. Participation of the ICU in personnel recruitment was nil. All the nurses with no or partial experience followed the orientation program (nursing supervisor interview, test of previous knowledge, handing over of the employee handbook, etc.), the theoretical and practical training program (supervision and tutorship) and the progressive responsibility program. More than half (63.6%) of the new nurses had another nurse duplicating their jobs during the training period and 54.5% of the new nurses attended the critical care course for nurses. Nurses participating in the orientation and training program expressed a high level of satisfaction. These measures helped nurses to decrease their stress and anxiety, increase and consolidate their knowledge, and provide safer care to critical patients. Conclusions: FMEA is a useful tool for improving ICU processes, even those involving human resources. The improvements implemented to decrease clinical risk related to the incorporation of new nurses in the ICU, based on previous training, will increase the safety of critical patient care by decreasing human errors due to inexperience (AU)