Improving Heart Failure Outcomes in Ambulatory and Community Care: A Scoping Study.

Despite a large body of literature testing interventions to improve heart failure care, care is often suboptimal. This scoping study assesses organizational interventions to improve heart failure outcomes in ambulatory settings. Fifty-two studies and systematic reviews assessing multicomponent, self-management support, and eHealth interventions were included. Studies dating from the 1990s demonstrated that multicomponent interventions could reduce hospitalizations, readmissions, mortality, and costs and improve quality of life. Self-management support appeared more effective when included in multicomponent interventions. The independent contribution of eHealth interventions remains unclear. No studies addressed management of comorbidities, geriatric syndromes, frailty, or end of life care. Few studies addressed risk stratification or vulnerable populations. Limited reporting about intervention components, implementation methods, and fidelity presents challenges in adapting this literature to scale interventions. The use of standardized reporting guidelines and study designs that produce more contextual evidence would better enable application of this work in health system redesign.

Luman/CREB3 recruitment factor regulates glucocorticoid receptor activity and is essential for prolactin-mediated maternal instinct.

The hypothalamic-pituitary-adrenal (HPA) axis is a major part of the neuroendocrine system in animal responses to stress. It is known that the HPA axis is attenuated at parturition to prevent detrimental effects of glucocorticoid secretion including inhibition of lactation and maternal responsiveness. Luman/CREB3 recruitment factor (LRF) was identified as a negative regulator of CREB3 which is involved in the endoplasmic reticulum stress response. Here, we report a LRF gene knockout mouse line that has a severe maternal behavioral defect. LRF(-/-) females lacked the instinct to tend pups; 80% of their litters died within 24 h, while most pups survived if cross-fostered. Prolactin levels were significantly repressed in lactating LRF(-/-) dams, with glucocorticoid receptor (GR) signaling markedly augmented. In cell culture, LRF repressed transcriptional activity of GR and promoted its protein degradation. LRF was found to colocalize with the known GR repressor, RIP140/NRIP1, which inhibits the activity by GR within specific nuclear punctates that are similar to LRF nuclear bodies. Furthermore, administration of prolactin or the GR antagonist RU486 restored maternal responses in mutant females. We thus postulate that LRF plays a critical role in the attenuation of the HPA axis through repression of glucocorticoid stress signaling during parturition and the postpartum period.