Telemedicine Support for Primary Care Providers versus Usual Care in Patients with Heart Failure: Protocol of a Pragmatic Cluster Randomised Trial within the Brazilian Heart Insufficiency with Telemedicine (BRAHIT) Study.

Heart failure is a prevalent condition and a frequent cause of hospital readmissions and poor quality of life. Teleconsultation support from cardiologists to primary care physicians managing patients with heart failure may improve care, but the effect on patient-relevant outcomes is unclear. We aim to evaluate whether collaboration through a novel teleconsultation platform in the Brazilian Heart Insufficiency with Telemedicine (BRAHIT) project, tested on a previous feasibility study, can improve patient-relevant outcomes. We will conduct a parallel-group, two-arm, cluster-randomised superiority trial with a 1:1 allocation ratio, with primary care practices from Rio de Janeiro as clusters. Physicians from the intervention group practices will receive teleconsultation support from a cardiologist to assist patients discharged from hospitals after admission for heart failure. In contrast, physicians from the control group practices will perform usual care. We will include 10 patients per each of the 80 enrolled practices (n = 800). The primary outcome will be a composite of mortality and hospital admissions after six months. Secondary outcomes will be adverse events, symptoms frequency, quality of life, and primary care physicians' compliance with treatment guidelines. We hypothesise that teleconsulting support will improve patient outcomes.

C/EBPα is required for long-term self-renewal and lineage priming of hematopoietic stem cells and for the maintenance of epigenetic configurations in multipotent progenitors.

Transcription factors are key regulators of hematopoietic stem cells (HSCs) and act through their ability to bind DNA and impact on gene transcription. Their functions are interpreted in the complex landscape of chromatin, but current knowledge on how this is achieved is very limited. C/EBPα is an important transcriptional regulator of hematopoiesis, but its potential functions in HSCs have remained elusive. Here we report that C/EBPα serves to protect adult HSCs from apoptosis and to maintain their quiescent state. Consequently, deletion of Cebpa is associated with loss of self-renewal and HSC exhaustion. By combining gene expression analysis with genome-wide assessment of C/EBPα binding and epigenetic configurations, we show that C/EBPα acts to modulate the epigenetic states of genes belonging to molecular pathways important for HSC function. Moreover, our data suggest that C/EBPα acts as a priming factor at the HSC level where it actively promotes myeloid differentiation and counteracts lymphoid lineage choice. Taken together, our results show that C/EBPα is a key regulator of HSC biology, which influences the epigenetic landscape of HSCs in order to balance different cell fate options.