Barriers and Facilitators to the Outpatient Management of Low-risk Pulmonary Embolism From the Emergency Department.

STUDY OBJECTIVE: Although recommended by professional society guidelines, outpatient management of low-risk pulmonary embolism (PE) from emergency departments (EDs) in the US remains uncommon. The objective of this study was to identify barriers and facilitators to the outpatient management of PE from the ED using implementation science methodology. METHODS: We conducted semistructured interviews with a purposeful sample of emergency physicians using maximum variation sampling, aiming to recruit physicians with diverse practice patterns regarding the management of low-risk PE. We developed an interview guide using the implementation science frameworks-the Consolidated Framework for Implementation Research and the Theoretical Domains Framework. Interviews were recorded, transcribed, and analyzed in an iterative process. RESULTS: We interviewed 26 emergency physicians from 11 hospital systems, and the participants were diverse with regard to years in practice, practice setting, and engagement with outpatient management of PE. Although outer setting determinants, such as medicolegal climate, follow-up, and insurance status were universal, our participants revealed that the importance of these determinants were moderated by individual-level and inner setting determinants. Prominent themes included belief in consequences, belief in capabilities, and institutional support and culture. Inertia of clinical practice and complexity of the process were important subthemes. CONCLUSION: In this qualitative study, clinicians reported common barriers and facilitators that initially focused on outer setting and external barriers but centered on clinician beliefs, fear, and local culture. Efforts to increase outpatient treatment of select patients with acute PE should be informed by these barriers and facilitators, which are aligned with the deimplementation theory.

Sensitivity of depression-like behavior to glucocorticoids and antidepressants is independent of forebrain glucocorticoid receptors.

The location of glucocorticoid receptors (GR) implicated in depression symptoms and antidepressant action remains unclear. Forebrain glucocorticoid receptor deletion on a C57B/6×129×CBA background (FBGRKO-T50) reportedly produces increased depression-like behavior and elevated glucocorticoids. We further hypothesized that forebrain GR deletion would reduce behavioral sensitivity to glucocorticoids and to antidepressants. We have tested this hypothesis in mice with calcium calmodulin kinase IIα-Cre-mediated forebrain GR deletion derived from a new founder on a pure C57BL/6 background (FBGRKO-T29-1). We measured immobility in forced swim or tail suspension tests after manipulating glucocorticoids or after dose response experiments with tricyclic or monoamine oxidase inhibitor antidepressants. Despite forebrain GR deletion that was at least as rapid and more extensive than reported in the mixed-strain FBGRKO-T50 mice (Boyle et al. 2005), and possibly because of their different founder, our FBGRKO-T29-1 mice did not exhibit increases in depression-like behavior or adrenocortical axis hormones. Nevertheless, FBGRKO-T29-1 mice were at least as sensitive as floxed GR controls to the depressive effects of glucocorticoids and the effects of two different classes of antidepressants. FBGRKO-T29-1 mice also unexpectedly exhibited increased mineralocorticoid receptor (MR) gene expression. Our results reinforce prior evidence that antidepressant action does not require forebrain GR, and suggest a correlation between the absence of depression-like phenotype and combined MR up-regulation and central amygdala GR deficiency. Our findings demonstrate that GR outside the areas targeted in FBGRKO-T29-1 mice are involved in the depressive effects of glucocorticoids, and leave open the possibility that these GR populations also contribute to antidepressant action.