Aliskiren, enalapril, or aliskiren and enalapril in heart failure

BACKGROUND Among patients with chronic heart failure, angiotensin-converting–enzyme (ACE) inhibitors reduce mortality and hospitalization, but the role of a renin inhibitor in such patients is unknown. We compared the ACE inhibitor enalapril with the renin inhibitor aliskiren (to test superiority or at least noninferiority) and with the combination of the two treatments (to test superiority) in patients with heart failure and a reduced ejection fraction. METHODS After a single-blind run-in period, we assigned patients, in a double-blind fashion, to one of three groups: 2336 patients were assigned to receive enalapril at a dose of 5 or 10 mg twice daily, 2340 to receive aliskiren at a dose of 300 mg once daily, and 2340 to receive both treatments (combination therapy). The primary composite outcome was death from cardiovascular causes or hospitalization for heart failure. RESULTS After a median follow-up of 36.6 months, the primary outcome occurred in 770 patients (32.9%) in the combination-therapy group and in 808 (34.6%) in the enalapril group (hazard ratio, 0.93; 95% confidence interval [CI], 0.85 to 1.03). The primary outcome occurred in 791 patients (33.8%) in the aliskiren group (hazard ratio vs. enalapril, 0.99; 95% CI, 0.90 to 1.10); the prespecified test for noninferiority was not met. There was a higher risk of hypotensive symptoms in the combination-therapy group than in the enalapril group (13.8% vs. 11.0%, P=0.005), as well as higher risks of an elevated serum creatinine level (4.1% vs. 2.7%, P=0.009) and an elevated potassium level (17.1% vs. 12.5%, P<0.001). CONCLUSIONS In patients with chronic heart failure, the addition of aliskiren to enalapril led to more adverse events without an increase in benefit. Noninferiority was not shown for aliskiren as compared with enalapri

Reasoning About a Service-oriented Programming Paradigm

This paper is about a new way for programming distributed applications: the service-oriented one. It is a concept paper based upon our experience in developing a theory and a language for programming services. Both the theoretical formalization and the language interpreter showed us the evidence that a new programming paradigm exists. In this paper we illustrate the basic features it is characterized by

Shared mental models and intra-team psychophysiological patterns: A test of the juggling paradigm

We explored implicit coordination mechanisms underlying the conceptual notion of "shared mental models" (SMM) through physiological (i.e., breathing and heart rates) and affective-cognitive (i.e., arousal, pleasantness, attention, self-efficacy, other's efficacy) monitoring of two professional jugglers performing a real-time interactive task of increasing difficulty. There were two experimental conditions: "individual" (i.e., solo task) and "interactive" (i.e., two jugglers established a cooperative interaction by juggling sets of balls with each other). In both conditions, there were two task difficulties: “easy” and “hard”. Descriptive analyses revealed that engaging in a dyadic cooperative motor task (interactive condition) required greater physiological effort (Median Cohen’s d = 2.13) than performing a solo motor task (individual condition) of similar difficulty. Our results indicated a strong positive correlation between the jugglers’ heart rate for the easy (r = .87) and hard tasks (r = .77). The relationship between the jugglers’ breathing rate was significant for the easy task (r = .73) but non-significant for the hard task. The findings are interpreted based on research on SMM and Theory of Mind. Practitioners should advance the notion of “shared-regulation” in the context of team coordination through the use of biofeedback training

Guidelines for pre-operative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery : the Task Force for Preoperative Cardiac Risk Assessment and Perioperative Cardiac Management in Non-cardiac Surgery of the European Society of Cardiology (ESC) and endorsed by the European Society of Anaesthesiology (ESA)

Non-cardiac surgery; Pre-operative cardiac risk assessment; Pre-operative cardiac testing; Pre-operative coronary artery revascularization; Perioperative cardiac management; Renal disease; Pulmonary disease; Neurological disease; Anaesthesiology; Post-operative cardiac surveillanc

Use of biologics for the management of Crohn's disease: IG-IBD clinical guidelines based on the GRADE methodology

A cure for Crohn's disease (CD), a chronic inflammatory disease of the gastrointestinal tract of unknown etiology, is not available, so patients require lifelong management to keep inflammation under control. The therapeutic armamentarium has expanded with approval of several biological drugs, including in-fliximab, adalimumab, vedolizumab and ustekinumab - monoclonal antibodies that target different in-flammatory pathways - and darvadstrocel, a suspension of expanded human allogeneic, adipose-derived, mesenchymal stromal cells for the treatment of refractory complex perianal fistula. Notwithstanding ex-isting practice guidelines on medical therapy for CD, the Italian Group for the Study of Inflammatory Bowel Disease felt the need to issue new guidelines focused on the use of biologics for managing the intestinal manifestations of CD and based on the GRADE methodology. This document presents recom-mendations regarding six clinical settings, from the induction to the maintenance of clinical remission, and from optimization and de-escalation of treatments to dealing with perianal CD and post-operative recurrence. The 19 evidence-based statements are supported by information on the quality of the evi-dence, agreement rate among panel members, and panel comments mainly based on evidence from real world studies

The Complex Relationship Between Serum Uric Acid, Endothelial Function and Small Vessel Remodeling in Humans

Aims: The relationship between serum uric acid (SUA) and microvascular remodeling in humans remains largely unexplored. We assessed whether SUA provides additional information on the severity of microvascular remodeling than that obtained from the European Heart Score (HS), the patterns of microvascular remodeling associated with changes in SUA levels and the mediation by endothelial function and nitric oxide (NO) availability on this relationship. Methods: A total of 162 patients included in the microvascular dataset of the Italian Society of Hypertension with available information on SUA, media-to-lumen (M/L) ratio, media cross-sectional area (MCSA), endothelial function, NO availability and HS were included in the analysis. The top tertile of M/L ratio and MCSA were used to define severe microvascular remodeling. Results: A U-shaped association was observed between SUA and both M/L ratio and MCSA. Adjustment for HS did not affect these associations. SUA was able to reclassify a significant number of subjects without, and with, severe M/L ratio and MCSA remodeling over the HS alone. The microvascular remodeling associated with SUA levels presented a predominant hypertrophic pattern. SUA was inversely associated with endothelial function and NO availability. Structural equation modeling analysis controlling for the HS suggested that the association of SUA with M/L ratio and MCSA was mediated through changes in endothelial function and NO availability. Conclusions: The addition of SUA to the HS improves the identification of subjects with greater microvascular remodeling. The relationship between SUA and microvascular remodeling is mediated by endothelial function and NO availability