Fondazione Mario Negri Sud

Santa Maria Imbaro, Italy

Fondazione Mario Negri Sud

Santa Maria Imbaro, Italy
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Macchia A.,Fondazione Mario Negri Sud | Mariani J.,Fundacion GESICA Grupo de Estudio de Investigacion Clinica en Argentina | Romero M.,Fondazione Mario Negri Sud | Robusto F.,Fondazione Mario Negri Sud | And 3 more authors.
European Journal of Clinical Pharmacology | Year: 2015

Purpose: Recent guidelines expand indications for statins. However, research on practical economic feasibility and cost-effectiveness in low-risk people is lacking. We aimed to describe the incidence of cardiovascular events (CVE), their total direct costs and the hypothetical effects of wide provision of statins on those rates and expenditures. Methods: We conducted a population-based cohort study using administrative data among low risk individuals. Estimators of effects of statins were taken from Cholesterol Treatment trialist metaanalysis and from Heart Protection Study trial. Two statin prices were used for analyses: National Italian Health System (€ 0.36) and the International Drug Price Indicator (€ 0.021). Results: Overall, 920,067 persons at low risk were identified and 14,849 CVE were registered (incidence rate 27.3 per 10,000 person-years). Direct costs for hospitalizations for CVE were 143 M €. Universal provision of statins would result in a significant decrease in CVE rates, from 27.3 to 17.5 per 10,000 person-years (PY) (95 % confidence interval (CI): 15.8-19.4). Universal prescription of simvastatin 20 mg would cost 802 M €. Otherwise, provision of simvastatin at International Drug Price Indicator's prices would be both clinically effective and cost saving in men older than age 44 (observed expenditures 120 M €, expected 97.4 M €) but not in women (observed expenditures 22.7 M €, expected 36.5 M €). Conclusions: Among a low-risk population, hypothetical universal provision of low-cost simvastatin to men over 44 years could be both clinically effective and a cost-saving strategy. © 2015 Springer-Verlag Berlin Heidelberg.


Cherubini V.,Salesi Hospital | Pintaudi B.,Fondazione Mario Negri Sud | Rossi M.C.,Fondazione Mario Negri Sud | Lucisano G.,Fondazione Mario Negri Sud | And 8 more authors.
Nutrition, Metabolism and Cardiovascular Diseases | Year: 2014

Background and aims: Evaluation of incidence and correlates of severe hypoglycemia (SH) and diabetes ketoacidosis (DKA) in children and adolescents with T1DM. Methods and results: Retrospective study conducted in 29 diabetes centers from November 2011 to April 2012. The incidence of SH and DKA episodes and their correlates were assessed through a questionnaire administered to parents of patients aged 0-18 years. Incidence rates and incident rate ratios (IRRs) were estimated through multivariate Poisson regression analysis and multilevel analysis. Overall, 2025 patients were included (age 12.4±3.8 years; 53% males; diabetes duration 5.6±3.5 years; HbA1c 7.9±1.1%). The incidence of SH and DKA were of 7.7 and 2.4events/100py, respectively. The risk of SH was higher in females (IRR=1.44; 95%CI 1.04-1.99), in patients using rapid acting analogues as compared to regular insulin (IRR=1.48; 95%CI 0.97-2.26) and lower for patients using long acting analogues as compared to NPH insulin (IRR=0.40; 95%CI 0.19-0.85). No correlations were found between SH and HbA1c levels. The risk of DKA was higher in patients using rapid acting analogues (IRR=4.25; 95%CI 1.01-17.86) and increased with insulin units needed (IRR=7.66; 95%CI 2.83-20.74) and HbA1c levels (IRR=1.63; 95%CI 1.36-1.95). Mother's age was inversely associated with the risk of both SH (IRR=0.95; 95%CI 0.92-0.98) and DKA (IRR=0.94; 95%CI 0.88-0.99). When accounting for center effect, the risk of SH associated with the use of rapid acting insulin analogues was attenuated (IRR=1.48; 95%CI 0.97-2.26); 33% and 16% of the residual variance in SH and DKA risk was explained by center effect. Conclusion: The risk of SH and DKA is mainly associated with treatment modalities and strongly depends on the practice of specialist centers. © 2013 Elsevier B.V.


Masson S.,Irccs Instituto Of Ricerche Farmacologiche Mario Negri | Caironi P.,University of Milan | Fanizza C.,Fondazione Mario Negri Sud | Caricato A.,University Cattolica Policlinico Universitario melli | And 6 more authors.
Critical Care Medicine | Year: 2016

Objectives: Myocardial dysfunction is a frequent complication in patients with severe sepsis and can worsen the prognosis. We investigated whether circulating biomarkers related to myocardial function and injury predicted outcome and were associated with albumin replacement. Design: A multicenter, randomized clinical trial about albumin replacement in severe sepsis or septic shock (the Albumin Italian Outcome Sepsis trial). Setting: Forty ICUs in Italy. Patients: Nine hundred and ninety-five patients with severe sepsis or septic shock. Interventions: Randomization to albumin and crystalloid solutions or crystalloid solutions alone. Measurements and Main Results: Plasma concentrations of N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin T were measured 1, 2, and 7 days after enrolment. We tested the relationship of single marker measurements or changes over time with clinical events, organ dysfunctions, albumin replacement, and ICU or 90-day mortality in the overall population and after stratification by shock. N-terminal pro-B-type natriuretic peptide levels were abnormal in 97.4% of the patients and high-sensitivity cardiac troponin T in 84.5%, with higher concentrations in those with shock. After extensive adjustments, N-terminal pro-B-type natriuretic peptide concentrations predicted ICU or 90-day mortality, better than high-sensitivity cardiac troponin T. Early changes in N-terminal pro-B-type natriuretic peptide or high-sensitivity cardiac troponin T concentrations were independently associated with subsequent mortality in patients with shock. Patients given albumin had significantly higher N-terminal pro-B-type natriuretic peptide levels; in addition, early rise in N-terminal pro-B-type natriuretic peptide was associated with a better outcome in this subgroup. Conclusions: Circulating N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin T are frequently elevated in severe sepsis or septic shock and have relevant prognostic value, which may be important in monitoring the clinical efficacy of supporting therapy. © 2016 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.


Degirolamo C.,IRCCS Instituto Oncologico Giovanni Paolo II | Rainaldi S.,Fondazione Mario Negri Sud | Bovenga F.,IRCCS Instituto Oncologico Giovanni Paolo II | Murzilli S.,Fondazione Mario Negri Sud | And 2 more authors.
Cell Reports | Year: 2014

Gut microbiota influences host health status by providing trophic, protective, and metabolic functions, including bile acid (BA) biotransformation. Microbial imprinting on BA signature modifies pool size and hydrophobicity, thus contributing to BA enterohepatic circulation. Microbiota-targeted therapies are now emerging as effective strategies for preventing and/or treating gut-related diseases. Here, we show that gut microbiota modulation induced by VSL#3 probiotics enhances BA deconjugation and fecal excretion in mice. These events are associated with changes in ileal BA absorption, repression of the enterohepatic farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) axis, and increased hepatic BA neosynthesis. Treatment with a FXR agonist normalized fecal BA levels in probiotic-administered mice, whereas probiotic-induced alterations in BA metabolism are abolished upon FXR and FGF15 deficiency. Our data provide clear invivo evidence that VSL#3 probiotics promote ileal BA deconjugation with subsequent fecal BA excretion and induce hepatic BA neosynthesis via downregulation of the gut-liver FXR-FGF15 axis. © 2014 The Authors.


Rossignol P.,French Institute of Health and Medical Research | Rossignol P.,University of Lorraine | Masson S.,Irccs Instituto Of Ricerche Farmacologiche Mario Negri | Barlera S.,Irccs Instituto Of Ricerche Farmacologiche Mario Negri | And 13 more authors.
European Journal of Heart Failure | Year: 2015

Aims Uncertainties remain on the biological and prognostic significance and therapeutic implications of loss in body weight (W-LOSS) in chronic heart failure (HF) patients. We assessed whether W-LOSS added additional prognostic value to classical clinical risk factors in two separate and large cohorts of patients with chronic HF. The factors associated with W-LOSS were studied. Methods and results W-LOSS and estimated plasma volume changes were measured serially in the GISSI-HF (n = 6820) and Val-HeFT trials (n = 4892). In both studies, experiencing at least one episode of ≥5% W-LOSS during the first year of follow-up was considered a sign of wasting. In GISSI-HF, self-reported unintentional W-LOSS ≥2 kg between two consecutive clinical visits within 1 year was also considered a sign of wasting. W-LOSS occurred in 16.4% and 15.7% of the patients enrolled in GISSI-HF and Val-HeFT, respectively (unintentional ≥2 kg W-LOSS occurred in 18.9% in GISSI-HF). In multivariable analyses adjusting for a number of baseline covariates as well as for plasma volume changes, W-LOSS was found to be independently associated with mortality and adverse cardiovascular and non-cardiovascular outcomes, with a significant net reclassification improvement (cfNRI) and an increase in integrated discrimination improvement (IDI). W-LOSS was independently associated with several features representing the severity of HF, including baseline NT-proBNP and high sensitivity C-reactive protein (hsCRP) in Val-HeFT. Conclusions W-LOSS was a frequent finding in the GISSI-HF and Val-HeFT trials, associated with multiple patient features, and added additional prognostic information beyond clinical variables of HF severity, including estimated plasma volume changes. © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.


Cindolo L.,S Pio Da Pietrelcina Hospital | Pirozzi L.,Fondazione Mario Negri Sud | Fanizza C.,Fondazione Mario Negri Sud | Romero M.,Fondazione Mario Negri Sud | And 4 more authors.
European Urology | Year: 2015

Background Little is known about drug adherence in men treated for lower urinary tract symptoms (LUTS). Benign prostatic hyperplasia (BPH) is one of the causes of LUTS. Objective To examine adherence to pharmacological therapy and its clinical value in men with LUTS. Design, setting, and participants Population-based cohort study using an administrative prescription database and hospital discharge codes for 1.5 million men aged ≥40 yr treated with alpha blockers (ABs) and 5-alpha reductase inhibitors (5ARIs) alone or in combination (CT). Interventions Therapy with ABs and/or 5ARIs. Outcome measurements and statistical analysis The 1-yr and long-term adherence; hospitalization rates for BPH and BPH surgery. Multivariate Cox proportional hazards regression model, propensity score matching, and sensitivity analyses. Results and limitations The 1-yr adherence was 29% in patients exposed to at least 6-mo therapy. Patients on CT had a higher discontinuation rate in the first 2 yr compared to those on monotherapy (p < 0.0001). Overall hospitalization rates for BPH and BPH surgery were 9.04 and 12.6 per 1000 patient-years, respectively. A lower risk of hospitalization was observed for 5ARI compared to AB therapy (hazard ratio [HR] 0.46 and 0.23; p < 0.0001). CT was associated with a reduced risk of hospitalization for BPH surgery (HR 0.94; p < 0.0001) compared to AB. Discontinuation of drug treatment was an independent risk factor for hospitalization for BPH and BPH surgery (HR 1.65 and 2.80; p < 0.0001) regardless of therapeutic group. Limitations include the paucity of clinical measures and the absence of patient-reported outcomes. Conclusions Adherence to pharmacological therapy for BPH is low and could affect clinical outcomes. Long-term 5ARI and CT use was associated with an independent reduced risk of hospitalization for BPH surgery. Our findings suggest the need for new strategies to increase patient adherence to prescribed treatment and more appropriate prescribing by physicians. Patient summary Our research shows that adherence to prescribed pharmacological therapy is crucial in the management of patients suffering from lower urinary tract symptoms. Moreover, pharmacological therapy can prevent disease progression. © 2014 European Association of Urology.


MacChia A.,Fundacion GESICA | Grancelli H.,Fundacion GESICA | Varini S.,Fundacion GESICA | Nul D.,Fundacion GESICA | And 8 more authors.
Journal of the American College of Cardiology | Year: 2013

Objectives: The aim of this study was to evaluate the efficacy of polyunsaturated fatty acids (n-3 PUFA) for the prevention of recurrent atrial fibrillation (AF) in patients with normal sinus rhythm. Background: Current pharmacological treatments to limit recurrent AF in patients with previous AF have limited efficacy and high rates of adverse events. Results of trials that tested the efficacy of n-3 PUFA provided heterogeneous results. Methods: This was a prospective, randomized, double-blind, placebo-controlled, multicenter trial involving 586 outpatient participants with confirmed symptomatic paroxysmal AF that required cardioversion (n = 428), at least 2 episodes of AF in the 6 months before randomization (n = 55), or both (103). Patients were randomly allocated to n-3 PUFA (1 g/day) or placebo for 12 months. The primary endpoint was symptomatic recurrence of AF. Results: There were no significant differences between patients allocated to placebo and those who received n-3 PUFA for the main outcome. At 12 months, 56 of 297 participants (18.9%) in the placebo group and 69 of 289 participants (24.0%) in the n-3 PUFA group had a recurrent symptomatic AF (hazard ratio: 1.28, 95% confidence interval: 0.90 to 1.83, p = 0.17). There was no difference between treatment with placebo and n-3 PUFA for any of the other pre-specified endpoints, including the composite of all-cause mortality, nonfatal stroke, nonfatal acute myocardial infarction, systemic embolism, heart failure development, or severe bleeding that occurred in 20 (6.7%) and 16 (5.5%) of patients randomized to placebo or n-3 PUFA, respectively (hazard ratio: 0.86, 95% confidence interval: 0.44 to 1.66, p = 0.65). Conclusions: Pharmacological supplementation with 1 g of n-3 PUFA for 1 year did not reduce recurrent AF. (Randomized Trial to Assess Efficacy of PUFA for the Maintenance of Sinus Rhythm in Persistent Atrial Fibrillation [FORWARD]; NCT00597220) © 2013 American College of Cardiology Foundation.


Vespasiani G.,Madonna del Soccorso Hospital | Rossi M.C.,Fondazione Mario Negri Sud
Frontiers in Diabetes | Year: 2015

A flexible therapy for type 1 diabetes based on carbohydrate counting and insulin dose adjustment can promote glycemic control and quality of life without worsening severe hypoglycemia or cardiovascular risk. The complexity of the standard education required by the flexible therapy can be managed with the 'Diabetes Interactive Diary (DID)', a carbohydrate/bolus calculator for mobile phones. It also works as a telemedicine system based on communication between patient and physician via text messages (SMS). The efficacy and safety of the DID have been tested in 3 main studies. The DID was demonstrated to be effective in improving metabolic control as well as standard education while ensuring several additional benefits. First, it halved the time dedicated to education and simplified the calculation of carbohydrates content and insulin doses, allowing more individuals with type 1 diabetes to adopt the flexible regimen. Second, the use of the DID was also associated with an 86% decrease in risk of grade 2 hypoglycemia. Additionally, several quality of life scales were significantly improved, suggesting that the use of telemedicine can increase the acceptance of insulin treatment and help patients cope with the disease. Currently, the DID is available as a free app for smartphones. © 2015 S. Karger AG, Basel.


PubMed | Fondazione Mario Negri Sud and University of Bari
Type: | Journal: Scientific reports | Year: 2016

The proliferative-crypt compartment of the intestinal epithelium is enriched in phospholipids and accumulation of phospholipids has been described in colorectal tumors. Here we hypothesize that biliary phospholipid flow could directly contribute to the proliferative power of normal and dysplastic enterocytes. We used Abcb4


Benvenga S.,Messina University | Pintaudi B.,Fondazione Mario Negri Sud | Vita R.,Messina University | Di Vieste G.,Messina University | Di Benedetto A.,Messina University
Journal of Clinical Endocrinology and Metabolism | Year: 2015

Context: Autoimmune thyroid diseases (AITDs) can be associated with type 1 diabetes (DM1). The prevalence of serum antibodies against thyroid hormones (THAb) in subjects with autoimmune diseases other than DM1 is increasing. No data are available for DM1. Objective: The objectives were evaluate the rate of associated AITD; the rate of positiveness for serum THAb; the panel of THAb based on thyroid hormone interaction and on Ig class; and the association of AITD alone, THAb alone, or AITD plus THAb with diabetes-related complications. Design: This was an observational, prospective study with 6-year (2005-2011) follow-up. Setting: The setting was an outpatient diabetes clinic. Patients: Fifty-two consecutive subjects (53.8% males; mean age, 37.4 ± 7.4 y; diabetes duration, 19.9 ± 8.2 y) with DM1. All participants completed the study. Main Outcome Measures: Main outcome measures were AITD rate; THAb positivity according to hormone interaction and Ig class; association of AITD and THAb with diabetes-related complications. Results: AITD rate increased from baseline (34.6%) to follow-up (38.5%). Subjects with DM1 had a high prevalence of THAb (92.3%). The presence of AITD at baseline was associated with subsequent development of macroangiopathy (0 vs 33% at baseline and follow-up, respectively; P = .029). Some THAb patterns, the majority having T3 binding in common, were associated with the progression and development of diabetes-related complications. Conclusions: THAb synthesis in DM1 might be driven by increased glycosylation of thyroglobulin. Anti T3-THAb may cause a relative "tissue hypothyroidism" by sequestering thyroid hormone, this at least partially contributing to worsening diabetes-related vascular complications. In a clinical setting THAb positivity could identify subjects more likely to develop diabetes complications. Copyright © 2015 by the Endocrine Society.

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