RESUMEN
Importance: The association of guideline-based decision support with the quality of care in patients with non-small cell lung cancer (NSCLC) is not known. Objective: To evaluate the association of exposure to the National Comprehensive Cancer Center (NCCN) guidelines with guideline-concordant care and patients' decisional conflict. Design, Setting, and Participants: A nonrandomized clinical trial, conducted at a tertiary care academic institution, enrolled patients from February 23, 2015, to September 28, 2017. Data analysis was conducted from July 19, 2019, to April 22, 2020. A cohort of 76 patients with NSCLC seen at diagnosis or disease progression and a retrospective cohort of 157 patients treated before the trial were included. Adherence to 6 NCCN recommendations were evaluated: (1) smoking cessation counseling, (2) adjuvant chemotherapy for patients with stage IB to IIB NSCLC after surgery, (3) pathologic mediastinal staging in patients with stage III NSCLC before surgery, (4) pathologic mediastinal staging in patients with stage III NSCLC before nonsurgical treatment, (5) definitive chemoradiotherapy for patients with stage III NSCLC not having surgery, and (6) molecular testing for epidermal growth factor receptor and anaplastic lymphoma kinase alterations for patients with stage IV NSCLC. Subgroup analysis was conducted to compare the rates of guideline concordance between the prospective and retrospective cohorts. Secondary end points included decisional conflict and satisfaction. Interventions: An online tool customizing the NCCN guidelines to patients' clinical and pathologic features was used during consultation, facilitated by a trained coordinator. Main Outcomes and Measures: Concordance of practice with 6 NCCN treatment recommendations on NSCLC and patients' decisional conflict. Results: Of the 76 patients with NSCLC, 44 were men (57.9%), median age at diagnosis was 68 years (interquartile range [IQR], 41-87 years), and 59 patients (77.6%) had adenocarcinoma. In the retrospective cohort, 91 of 157 patients (58.0%) were men, median age at diagnosis was 66 years (IQR, 61-65 years), and 105 patients (66.9%) had adenocarcinoma. After the intervention, patients received more smoking cessation counseling (4 of 5 [80.0%] vs 1 of 24 [4.2%], P < .001) and less adjuvant chemotherapy (0 of 7 vs 7 of 11 [63.6%]; P = .012). There was no significant change in mutation testing of non-squamous cell stage IV disease (20 of 20 [100%] vs 48 of 57 [84.2%]; P = .10). There was no significant change in pathologic mediastinal staging or initial chemoradiotherapy for patients with stage III disease. After consultation with the tool, decisional conflict scores improved by a median of 20 points (IQR, 3-34; P < .001). Conclusions and Relevance: The findings of this study suggest that exposure to the NCCN guidelines is associated with increased guideline-concordant care for 2 of 6 preselected recommendations and improvement in decisional conflict. Trial Registration: ClinicalTrials.gov Identifier: NCT03982459.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Sistemas de Apoyo a Decisiones Clínicas , Neoplasias Pulmonares , Calidad de Vida , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/psicología , Adenocarcinoma del Pulmón/terapia , Anciano , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/psicología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Atención Integral de Salud/métodos , Atención Integral de Salud/normas , Técnicas de Apoyo para la Decisión , Femenino , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/psicología , Neoplasias Pulmonares/terapia , Masculino , Estadificación de Neoplasias/métodos , Satisfacción del Paciente , Guías de Práctica Clínica como Asunto , Pronóstico , Calidad de la Atención de Salud/normas , Evaluación de Síntomas/métodosRESUMEN
The POU domain transcription factors Oct-1 and Oct-2 interact with the octamer element, a motif conserved within Ig promoters and enhancers, and mediate transcription from the Ig loci. Inactivation of Oct-2 by gene targeting results in normal B cell development and Ig transcription. To study the role of Oct-1 in these processes, the lymphoid compartment of RAG-1(-/-) animals was reconstituted with Oct-1-deficient fetal liver hematopoietic cells. Recipient mice develop B cells with levels of surface Ig expression comparable with wild type, although at slightly reduced numbers. These B cells transcribe Ig normally, respond to antigenic stimulation, undergo class switching, and use a normal repertoire of light chain variable segments. However, recipient mice show slight reductions in serum IgM and IgA. Thus, the Oct-1 protein is dispensable for B cell development and Ig transcription.
Asunto(s)
Linfocitos B/citología , Linfocitos B/metabolismo , Proteínas de Unión al ADN/deficiencia , Regulación de la Expresión Génica/genética , Inmunoglobulinas/genética , Factores de Transcripción/deficiencia , Transcripción Genética/genética , Traslado Adoptivo , Animales , Linfocitos B/inmunología , División Celular , Línea Celular Transformada , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Embrión de Mamíferos/embriología , Embrión de Mamíferos/metabolismo , Eliminación de Gen , Genes RAG-1/genética , Factor C1 de la Célula Huésped , Cadenas Pesadas de Inmunoglobulina/biosíntesis , Cadenas Pesadas de Inmunoglobulina/genética , Cadenas Ligeras de Inmunoglobulina/biosíntesis , Cadenas Ligeras de Inmunoglobulina/genética , Inmunoglobulinas/biosíntesis , Inmunoglobulinas/sangre , Ratones , Ratones Noqueados , Factor 1 de Transcripción de Unión a Octámeros , Fenotipo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Oct-1 is a sequence-specific DNA binding transcription factor that is believed to regulate a large group of tissue-specific and ubiquitous genes. Both Oct-1 and the related but tissue-restricted Oct-2 protein bind to a DNA sequence termed the octamer motif (5'-ATGCAAAT-3') with equal affinity in vitro. To address the role of Oct-1 in vivo, an Oct-1-deficient mouse strain was generated by gene targeting. Oct-1-deficient embryos died during gestation, frequently appeared anemic, and suffered from a lack of Ter-119-positive erythroid precursor cells. This defect was cell intrinsic. Fibroblasts derived from these embryos displayed a dramatic decrease in Oct-1 DNA binding activity and a lack of octamer-dependent promoter activity in transient transfection assays. Interestingly, several endogenous genes thought to be regulated by Oct-1 showed no change in expression. When crossed to Oct-2(+/-) animals, transheterozygotes were recovered at a very low frequency. These findings suggest a critical role for Oct-1 during development and a stringent gene dosage effect with Oct-2 in mediating postnatal survival.
Asunto(s)
Proteínas de Unión al ADN/deficiencia , Pérdida del Embrión/genética , Eritropoyesis/genética , Genes Letales , Regiones Promotoras Genéticas , Factores de Transcripción/deficiencia , Animales , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Eritropoyesis/fisiología , Marcación de Gen , Globinas/biosíntesis , Globinas/genética , Heterocigoto , Factor C1 de la Célula Huésped , Ratones , Mutación , Factor 1 de Transcripción de Unión a Octámeros , Factor 2 de Transcripción de Unión a Octámeros , Análisis de Secuencia de ADN , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Expression of the herpes simplex virus (HSV) immediate early (IE) genes is regulated by a multiprotein complex that is assembled on the TAATGARAT enhancer core element. The complex contains the cellular POU domain protein Oct-1, the viral transactivator VP16, and the cellular cofactor host cell factor 1. The current model suggests that the assembly depends on recognition of the core element by Oct-1. Here, HSV infection of Oct-1-deficient mouse embryonic fibroblast cells demonstrates that Oct-1 is critical for IE gene expression at low multiplicities of infection (moi). However, the protein is not essential for IE gene expression at high moi, indicating that VP16-mediated transcriptional induction through other IE regulatory elements is also important. This induction depends, at least in part, on the GA-binding protein binding elements that are present in each IE enhancer domain. Surprisingly, whereas the viral IE genes are expressed after high moi infection of Oct-1-deficient cells, the assembly of viral replication factories is severely impaired, revealing a second critical role for Oct-1 in HSV replication. The results have implications for both the HSV lytic and latency-reactivation cycles.