The ERM experience of the Lombardy Region as a tool for improving the safety of the regional health care system.

The Regional Center for Healthcare Risk Management and Patient Safety of the Lombardy Region, with the technical partnership of Aon, designed an innovative Healthcare Enterprise Risk Management Model (hereafter HERM) to meet the following objectives: 1) Improve the safety of the Regional Healthcare System through the implementation of methods and tools aimed to identify, analyze and mange in an integrated way all the risks to which are exposed the healthcare companies. 2) Preserve the creation of social value in the medium-long term and the sustainable achievement of strategic and operational objectives. 3) Optimize risk management costs. 4) Reduce/mitigate adverse events in all business processes. 5) Enable the ability to anticipate and react to changes. 6) Establish sound long-term and risk-based strategies. This paper describes the structuring of the overall HERM Model Framework, and the related information flows, the tools supporting the Healthcare Enterprise Risk Management Methodology (such as the Risk Model and the Assessment Metrics) and presents the preliminary result of first experience of Healthcare ERM in Italy.

A novel truncated form of eNOS associates with altered vascular function.

AIMS: Nitric oxide (NO) plays a key role in vascular homeostasis and is produced by endothelial NO synthase (eNOS), encoded by NOS3 gene. We previously reported the genetic association between NOS3 rs753482-A>C polymorphism on intron 19 and coronary artery disease (CAD). In the attempt of conferring functional implication to the rs753482-A>C polymorphism, we investigated its influence on transcript maturation. METHODS AND RESULTS: A transcript variant skipping exons 20-21 is prevalent in carriers of the rs753482-C allele and is translated in a novel truncated form of eNOS. The truncated eNOS displays increased basal NO production, is insensitive to calcium stimulation, and, upon heterodimerization with the full-length eNOS protein, exerts a dominant-negative effect on NO production. CAD patients and healthy subjects' carriers of the rs753482-C genotype are characterized by increased NO basal levels in peripheral blood and platelets, and negatively respond to oral glucose load by failing to increase NO synthesis following insulin wave. Furthermore, forearm vasodilation after reactive hyperaemia is dramatically impaired in rs753482-C carriers. CONCLUSIONS: We demonstrated that subjects carrying the rs753482-C genotype express a novel stable truncated form of eNOS with altered enzymatic activity that influences NO production and endothelial function. These findings open to new intriguing perspectives to several diseases involving vascular response to NO.

Mid-term results of tricuspid annuloplasty with a three-dimensional remodelling ring.

OBJECTIVE: To assess the results of tricuspid annuloplasty performed with the Edwards MC3 remodeling ring. METHODS: From 2005 to 2007, 140 patients with tricuspid regurgitation (TR) secondary to left-sided valve disease (mean age 63.8 ± 11.6, permanent pacemaker in 7.8%, LVEF 56.4 ± 10.1%, LVEDD 54.1 ± 8 mm, SPAP 52.5 ± 14.4 mmHg) underwent tricuspid annuloplasty using the MC3 ring. Dilatation of the tricuspid annulus was present in all patients. Other concomitant mechanisms of TR (moderate leaflet prolapse, pacemaker wires, leaflets' retraction) were documented in 21 cases (15%). All patients underwent concomitant left-sided valve surgery. Ring size was between 28 and 32 in 84.3% of patients. RESULTS: Hospital mortality was 3.5% and actuarial survival at 3 years 94.8 ± 2.1%. Mean follow-up of the 135 hospital survivors was 22 ± 9.5 months (median 23 months). Echocardiography at hospital discharge documented no or mild TR in 119 patients (87%), moderate TR (2+/4+) in 15 (11%) and moderate-to-severe (3+/4+) in 1 patient (0.7%). At echocardiographic follow-up moderate TR was present in 14 patients (10.3%) and moderate-to-severe TR in 2 (1.4%). At 3 years freedom from TR ≥ 2+ was 88.1 ± 2.78% and freedom from TR ≥ 3+ was 94.3 ± 4.89. Predictors of TR ≥ 2+ at hospital discharge and at follow-up were preoperative LVEF (OR:0.8; p = 0.001 at discharge; HR:0.9; p = 0.003 at follow-up) and the presence of other mechanisms of TR besides annular dilatation (OR:10.8; p = 0.007 at discharge; HR:6.1; p = 0.003 at follow-up). CONCLUSION: Tricuspid annuloplasty with the MC3 ring provides satisfactory early results which remain stable at mid-term follow-up. The presence of other mechanisms besides annular dilatation leads to residual valve insufficiency after ring annuloplasty alone.

Oral L-arginine supplementation improves endothelial function and ameliorates insulin sensitivity and inflammation in cardiopathic nondiabetic patients after an aortocoronary bypass.

It is known that L-arginine treatment can ameliorate endothelial dysfunction and insulin sensitivity in type 2 diabetes mellitus patients, but little is known on L-arginine effects on these variables in nondiabetic patients with stable cardiovascular disease (coronary artery disease). We evaluated the effects of long-term oral L-arginine treatment on endothelial dysfunction, inflammation, adipokine levels, glucose tolerance, and insulin sensitivity in these patients. Sixty-four patients with cardiovascular disease previously submitted to an aortocoronary bypass and not known for type 2 diabetes mellitus had an oral glucose load to define their glucose tolerance. Thirty-two patients with nondiabetic response were eligible to receive, in a double-blind randomized parallel order, L-arginine (6.4 g/d) or placebo for 6 months. An evaluation of insulin sensitivity index during the oral glucose load, markers of systemic nitric oxide bioavailability and inflammation, and blood flow was performed before and at the end of the treatment in both groups. Compared with placebo, L-arginine decreased asymmetric dimethylarginine levels (P < .01), indices of endothelial dysfunction, and increased cyclic guanosine monophosphate (P < .01), L-arginine to asymmetric dimethylarginine ratio (P < .0001), and reactive hyperemia (P < .05). Finally, L-arginine increased insulin sensitivity index (P < .05) and adiponectin (P < .01) and decreased interleukin-6 and monocyte chemoattractant protein-1 levels. In conclusion, insulin resistance, endothelial dysfunction, and inflammation are important cardiovascular risk factors in coronary artery disease patients; and L-arginine seems to have anti-inflammatory and metabolic advantages in these patients.

A randomized clinical trial of trimetazidine, a partial free fatty acid oxidation inhibitor, in patients with heart failure.

OBJECTIVES: This study sought to assess whether the long-term addition of trimetazidine to conventional treatment could improve functional class, exercise tolerance, and left ventricular function in patients with heart failure (HF). BACKGROUND: Previous small studies have shown that trimetazidine may be beneficial in terms of left ventricular function preservation and control of symptoms in patients with post-ischemic HF. METHODS: Fifty-five patients with HF were randomly allocated in an open-label fashion to either conventional therapy plus trimetazidine (20 mg three times daily) (28 patients) or conventional therapy alone (27 patients). Mean follow-up was 13 +/- 3 months. At study entry and at follow-up, all patients underwent exercise testing and two-dimensional echocardiography. Among the others, New York Heart Association (NYHA) functional class and ejection fraction (EF) were evaluated. RESULTS: In the trimetazidine group, NYHA functional class significantly improved compared with the conventional therapy group (p < 0.0001). Treatment with trimetazidine significantly decreased left ventricular end-systolic volume (from 98 +/- 36 ml to 81 +/- 27 ml, p = 0.04) and increased EF from 36 +/- 7% to 43 +/- 10% (p = 0.002). On the contrary, in the conventional therapy group, both left ventricular end-diastolic and -systolic volumes increased from 142 +/- 43 ml to 156 +/- 63 ml, p = 0.2, and from 86 +/- 34 ml to 104 +/- 52 ml, p = 0.1, respectively; accordingly, EF significantly decreased from 38 +/- 7% to 34 +/- 7% (p = 0.02). CONCLUSIONS: In conclusion, long-term trimetazidine improves functional class and left ventricular function in patients with HF. This benefit contrasts with the natural history of the disease, as shown by the decrease of EF in patients on standard HF therapy alone.