Dentali F.,University of Insubria |
Mumoli N.,Ospedale Civile di Livorno |
Prisco D.,University of Florence |
Fontanella A.,Ospedale Fatebenefratelli |
Di Minno M.N.D.,University of Naples Federico II
Thrombosis and Haemostasis | Year: 2017
Compelling evidence suggests that the risk of pulmonary embolism (PE) and deep-vein thrombosis (DVT) persists after hospital discharge in acutely-ill medical patients. However, no studies consistently supported the routine use of extended-duration thromboprophylaxis (ET) in this setting. We performed a meta-analysis to assess efficacy and safety of ET in acutely-ill medical patients. Efficacy outcome was defined by the prevention of symptomatic DVT, PE, venous thromboembolism (VTE) and VTE-related mortality. Safety outcome was the occurrence of major bleeding (MB) and fatal bleeding (FB). Pooled odds ratios (ORs) and 95 % confidence intervals (95 %CI) were calculated for each outcome using a random effects model. Four RCTs for a total of 28,105 acutely-ill medical patients were included. ET was associated with a significantly lower risk of DVT (0.3 % vs 0.6 %, OR 0.504, 95 %CI: 0.287-0.885) and VTE (0.5 % vs 1.0 %, OR: 0.544, 95 %CI: 0.297-0.997); a non-significantly lower risk of PE (0.3 % vs 0.4 %, OR 0.633, 95 %CI: 0.388-1.034) and of VTE-related mortality (0.2 % vs 0.3 %, OR 0.687, 95 %CI: 0.445-1.059) and with a significantly higher risk of MB (0.8 % vs 0.4 %, OR 2.095, 95 %CI: 1.333-3.295). No difference in FB was found (0.06 % vs 0.03 %, OR 1.79, 95 %CI: 0.384-8.325). The risk benefit analysis showed that the NNT for DVT was 339, for VTE was 239, and the NNH for MB was 247. Results of our meta-analyses focused on clinical important outcomes did not support a general use of antithrombotic prophylaxis beyond the period of hospitalization in acutely-ill medical patients. © Schattauer 2017.
Ferreri F.,Kuopio University Hospital |
Ferreri F.,Biomedical University of Rome |
Ponzo D.,Biomedical University of Rome |
Hukkanen T.,Kuopio University Hospital |
And 7 more authors.
Journal of Neurophysiology | Year: 2012
When linking in time electrical stimulation of the peripheral nerve with transcranial magnetic stimulation (TMS), the excitability of the motor cortex can be modulated to evoke clear inhibition, as reflected by the amplitude decrement in the motor-evoked potentials (MEPs). This specific property, designated short-latency afferent inhibition (SAI), occurs when the nerve-TMS interstimulus interval (ISI) is approximately 25 ms and is considered to be a corticothalamic phenomenon. The aim of the present study was to use the electroencephalographic (EEG) responses to navigated-TMS coregistration to better characterize the neuronal circuits underlying SAI. The present experimental set included magnetic resonance imaging (MRI)-navigated TMS and 60- channel TMS-compatible EEG devices. TMS-evoked EEG responses and MEPs were analyzed in eight healthy volunteers; ISIs between median nerve and cortical stimulation were determined relative to the latency of the individual N20 component of the somatosensoryevoked potential (SEP) obtained after stimulation of the median nerve. ISIs from the latency of the N20 plus 3 ms and N20 plus 10 ms were investigated. In all experimental conditions, TMS-evoked EEG responses were characterized by a sequence of negative deflections peaking at approximately 7, 44, and 100 ms alternating with positive peaks at approximately 30, 60, and 180 ms post-TMS. Moreover, ISI N20+3 ms modulated both EEG-evoked activity and MEPs. In particular, it inhibited MEP amplitudes, attenuated cortical P60 and N100 responses, and induced motor cortex beta rhythm selective decrement of phase locking. The findings of the present experiment suggest the cortical origin of SAI that could result from the cortico- cortical activation of GABAergic-mediated inhibition onto the corticospinal neurons modulated by cholinergic activation able to reducing intralaminar inhibition and promoting intracolumnar inhibition. © 2012 by the American Physiological Society.
Citro R.,University of Salerno |
Rigo F.,DellAngelo Hospital |
Previtali M.,University of Pavia |
Ciampi Q.,Ospedale Fatebenefratelli |
And 8 more authors.
Journal of the American Geriatrics Society | Year: 2012
Objectives To describe the clinical characteristics and in-hospital outcomes of older adults with tako-tsubo cardiomyopathy (TTC). Design Partially retrospective, partially prospective observational study. Setting Eleven Italian referral cardiac centers included in the Tako-tsubo Italian Network. Participants One hundred ninety consecutive individuals with TTC (92.1% female, mean age 66) were divided into three groups according to age (<65, n = 78; 65-74, n = 61; ≥75, n = 51). Measurements Clinical findings and in-hospital outcomes were evaluated in each group. Results Participants aged 65 and older had a greater prevalence of hypertension (P =.001) and a lower glomerular filtration rate (P <.001), and those aged 65 to 74 had a greater prevalence of psychiatric disorders (P =.01), ST-segment elevation on admission (P =.01) and a cerebrovascular disease (P =.003) than those younger than 65. Despite similar left ventricular ejection fraction (LVEF) on admission (P =.26), the oldest group had a lower LVEF at discharge (P =.03). Inotropic agents were used more frequently in older adults (P =.03). In-hospital composite adverse events (all-cause death, acute heart failure, life-threatening arrhythmias, stroke, and cardiogenic shock; P =.03) and overall complications (P =.004) were more common in participants aged 75 and older. Overall in-hospital mortality was low (2.8%) but was more prevalent in participants aged 75 and older (6.3%). On multivariate analysis, age of 75 and older (hazard ratio (HR) = 2.45, 95% confidence interval (CI) = 1.28-5.82, P =.04) and LVEF on admission (HR = 0.874, 95% CI = 0.81-0.95, P <.001) were the only independent predictors of in-hospital adverse events. Conclusion The clinical profile of participants aged 75 and older with TTC was different from that of those younger than 75 with TTC, and they had a higher in-hospital complication rate. © 2011, The American Geriatrics Society.
Valgimigli M.,University of Bern |
Valgimigli M.,Erasmus Medical Center |
Frigoli E.,EUSTRATEGY Association |
Leonardi S.,Unita Operativa Complessa Cardiologia |
And 33 more authors.
New England Journal of Medicine | Year: 2015
BACKGROUND Conflicting evidence exists on the efficacy and safety of bivalirudin administered as part of percutaneous coronary intervention (PCI) in patients with an acute coronary syndrome. METHODS We randomly assigned 7213 patients with an acute coronary syndrome for whom PCI was anticipated to receive either bivalirudin or unfractionated heparin. Patients in the bivalirudin group were subsequently randomly assigned to receive or not to receive a post-PCI bivalirudin infusion. Primary outcomes for the comparison between bivalirudin and heparin were the occurrence of major adverse cardiovascular events (a composite of death, myocardial infarction, or stroke) and net adverse clinical events (a composite of major bleeding or a major adverse cardiovascular event). The primary outcome for the comparison of a post-PCI bivalirudin infusion with no post-PCI infusion was a composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events. RESULTS The rate of major adverse cardiovascular events was not significantly lower with bivalirudin than with heparin (10.3% and 10.9%, respectively; relative risk, 0.94; 95% confidence interval [CI], 0.81 to 1.09; P = 0.44), nor was the rate of net adverse clinical events (11.2% and 12.4%, respectively; relative risk, 0.89; 95% CI, 0.78 to 1.03; P = 0.12). Post-PCI bivalirudin infusion, as compared with no infusion, did not significantly decrease the rate of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events (11.0% and 11.9%, respectively; relative risk, 0.91; 95% CI, 0.74 to 1.11; P = 0.34). CONCLUSIONS In patients with an acute coronary syndrome, the rates of major adverse cardiovascular events and net adverse clinical events were not significantly lower with bivalirudin than with unfractionated heparin. The rate of the composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events was not significantly lower with a post-PCI bivalirudin infusion than with no post-PCI infusion. (Funded by the Medicines Company and Terumo Medical; MATRIX ClinicalTrials.gov number, NCT01433627.) Copyright © 2015 Massachusetts Medical Society. All rights reserved.
PubMed | Johannes Gutenberg University Mainz, University of Insubria, Ospedale Maggiore della Carita, Ospedale Civile di Livorno and Ospedale Fatebenefratelli
Type: | Journal: Internal and emergency medicine | Year: 2016
The decision concerning the introduction of primary and secondary prophylaxis of venous thromboembolism (VTE) in patients with solid brain neoplasms and brain metastases is often challenging due to the concomitant increasedrisk of intracranial hemorrhage and to limited evidence from available literature. A standardized questionnaire composed of nine multiple-choice questions regarding primary VTE prevention in non-surgical patients during high-risk conditions and VTE secondary prevention in patients with a solid brain neoplasm or cerebral metastases was sent via electronic mail to all the members (n=2420) of the Italian Federation of the Internal Medicine Hospital Executives Associations (FADOI) in June 2015. Three hundred and fifty two physicians (14.5%) returned it (participants median age 51years; females 46.9%). The majority of respondents prescribe primary thromboprophylaxis (usually with heparin) in non-surgical patients with solid brain neoplasms and brain metastases in concomitance with high-risk conditions. Full-dose anticoagulation with either low-molecular-weight heparin or fondaparinux is the preferred option for acute VTE (69.6%), while a reduced dose is chosen by 21.0% of physicians. The presence of a highly vascular brain neoplasm histotype mandates the prescription of a reduced-dose antithrombotic regimen in a minority of respondents. Vena cava filter placement is an option for the treatment of acute VTE in more than 6% of respondents. Anticoagulants are often prescribed for both VTE primary prevention and treatment. In conclusion, physicians managements are partially in contrast to recent guidelines, reinforcing the need for educational programs and other studies in this setting.
PubMed | Ospedale S. Chiara, Ospedale Cannizzaro, Ospedale S. Giovanni Calibita Fatebenefratelli, Fondazione IRCCS Instituto Nazionale dei Tumori and 10 more.
Type: Journal Article | Journal: Oncotarget | Year: 2016
No biomarker is available to predict prognosis of patients with advanced ovarian cancer (AOC) and guide the choice of chemotherapy. We performed a prospective-retrospective biomarker study within the MITO2 trial on the treatment of AOC.MITO2 is a randomised multicentre phase 3 trial conducted with 820 AOC patients assigned carboplatin/paclitaxel (carboplatin: AUC5, paclitaxel: 175 mg/m, every 3 weeks for 6 cycles) or carboplatin/PLD-pegylated liposomal doxorubicin (carboplatin: AUC5, PLD: 30 mg/m, every 3 weeks for 6 cycles) as first line treatment. Sixteen biomarkers (pathways of adhesion/invasion, apoptosis, transcription regulation, metabolism, and DNA repair) were studied in 229 patients, in a tissue microarray. Progression-free and overall survival were analysed with multivariable Cox model.After 72 months median follow-up, 594 progressions and 426 deaths were reported; there was no significant difference between the two arms in the whole trial. No biomarker had significant prognostic value. Statistically significant interactions with treatment were found for DNA-dependent protein kinase (DNA-PK) and phosphorylated acetyl-coenzymeA carboxylase (pACC), both predicting worse outcome for patients receiving carboplatin/paclitaxel.These data show that in presence of DNA-PK or pACC overexpression, carboplatin/paclitaxel might be less effective than carboplatin/PLD as first line treatment of ovarian cancer patients. Further validation of these findings is warranted.
Acute kidney injury after percutaneous coronary intervention: Rationale of the AKI-MATRIX (acute kidney injury-minimizing adverse hemorrhagic events by TRansradial access site and systemic implementation of angioX) sub-study
Ando G.,Messina University |
Cortese B.,Ospedale Fatebenefratelli |
Frigoli E.,EUSTRATEGY Association |
Gagnor A.,Cardiology Unit |
And 5 more authors.
Catheterization and Cardiovascular Interventions | Year: 2015
Acute kidney injury (AKI) is an important complication of both diagnostic cardiac catheterization and percutaneous coronary intervention (PCI). A large body of evidence supports that AKI is related to volume of contrast used. Despite several measures are available to reduce the impact of contrast media on AKI, its incidence remains significant as other mechanisms of renal damage are involved. A new paradigm is established according to which bleeding prevention is at least as important as preventing recurrent ischemic events in the management of patients with acute coronary syndromes (ACS) undergoing an invasive approach. Periprocedural bleeding, which is consistently reduced by radial approach, is emerging as a risk factor for the development of AKI. Therefore, the role of vascular access as a measure to prevent AKI needs to be systematically assessed in randomized studies. To date, no prospective comparison on renal outcomes has been carried out in randomized trials between radial and femoral approach. The Minimizing Adverse hemorrhagic events by TRansradial access site and systemic Implementation of AngioX (MATRIX) trial (ClinicalTrials.gov identifier: NCT01433627) has been designed to test whether to minimize bleeding events by using radial access and bivalirudin, across the whole spectrum of patients with ACS undergoing PCI, will result in improved outcomes with respect to both ischemic and bleeding complications. The AKI-MATRIX sub-study will provide a unique opportunity to assess whether the advantages of radial approach may even contribute to the reduction of the risk of AKI in patients with ACS. © 2015 Wiley Periodicals, Inc.
Fiorino C.,San Raffaele Scientific Institute |
Rancati T.,Fondazione IRCCS Instituto Nazionale Dei Tumori |
Fellin G.,Ospedale Santa Chiara |
Vavassori V.,Cliniche Humanitas Gavazzeni |
And 8 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2012
Purpose: To model late fecal incontinence after high-dose prostate cancer radiotherapy (RT) in patients accrued in the AIROPROS (prostate working group of the Italian Association of Radiation Oncology) 0102 trial using different endpoint definitions. Methods and Materials: The self-reported questionnaires (before RT, 1 month after RT, and every 6 months for ≤3 years after RT) of 586 patients were available. The peak incontinence (P-INC) and two longitudinal definitions (chronic incontinence [C-INC], defined as the persistence of Grade 1 or greater incontinence after any Grade 2-3 event; and mean incontinence score [M-INC], defined as the average score during the 3-year period after RT) were considered. The correlation between the clinical/dosimetric parameters (including rectal dose-volume histograms) and P-INC (Grade 2 or greater), C-INC, and M-INC of ≥1 were investigated using multivariate logistic analyses. Receiver operating characteristic curves and the area under the curve were used to assess the predictive value of the different multivariate models. Results: Of the 586 patients, 36 with a Grade 1 or greater incontinence score before RT were not included in the present analysis. Of the 550 included patients, 197 (35.8%) had at least one control with a Grade 1 or greater incontinence score (M-INC >0). Of these 197 patients, 37 (6.7%), 22 (4.0%), and 17 (3.1%) were scored as having P-INC, M-INC ≥1, and C-INC, respectively. On multivariate analysis, Grade 2 or greater acute incontinence was the only predictor of P-INC (odds ratio [OR], 5.9; p =.0009). Grade 3 acute incontinence was predictive of C-INC (OR, 9.4; p =.02), and percentage of the rectal volume receiving >40 Gy of ≥80% was predictive of a M-INC of ≥1 (OR, 3.8; p =.008) and of C-INC (OR, 3.6; p =.03). Previous bowel disease, previous abdominal/pelvic surgery, and the use of antihypertensive (protective factor) correlated highly with both C-INC and M-INC ≥1. The predictive values of the models for C-INC (area under the curve, 0.83) and M-INC ≥1 (area under the curve, 0.73) were greater than the ones for P-INC (area under the curve, 0.62) and more reliable (p =.0001-.0003 against p =.02). Nomograms for the two longitudinal definitions were derived. Conclusions: The longitudinal definitions of fecal incontinence (C-INC and M-INC ≥1) were helpful in accounting for both the persistence and the severity of the incontinence. A significant fraction of peak events was consequential to acute incontinence, and a longer duration of symptoms mainly depended on the rectal dose bath (percentage of rectal volume receiving >40 Gy), and pretreatment clinical factors. © 2012 Elsevier Inc. All rights reserved.
Valgimigli M.,Erasmus University Rotterdam |
Calabro P.,The Second University of Naples |
Cortese B.,Ospedale FatebeneFratelli |
Frigoli E.,Cardiostudy |
And 12 more authors.
Journal of Cardiovascular Translational Research | Year: 2014
Early invasive management and the use of combined antithrombotic therapies have decreased the risk of recurrent ischaemia in patients with acute coronary syndrome (ACS) but have also increased the bleeding risk. Transradial intervention (TRI) and bivalirudin infusion compared to transfemoral intervention (TFI) or unfractionated heparin (UFH) plus glycoprotein IIb/IIIa inhibitors (GPI) decrease bleeding complications in patients with ACS. To what extent, a bleeding preventive strategy incorporating at least one of these two treatment options translates into improved outcomes is a matter of debate. The Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX study is a large-scale, multicenter, prospective, open-label trial, conducted at approximately 100 sites in Europe aiming to primarily assess whether TRI and bivalirudin infusion, as compared to TFI and UFH plus provisional GPI, decrease the 30-day incidence of death, myocardial infarction or stroke across the whole spectrum of ACS patients. © 2014 Springer Science+Business Media New York.
Mencacci C.,Ospedale Fatebenefratelli |
Di Sciascio G.,Azienda Ospedaliera Universitaria |
Katz P.,CSD Medical Research Srl |
Ripellino C.,CSD Medical Research Srl
ClinicoEconomics and Outcomes Research | Year: 2013
Background: Depression has a lifetime prevalence of 10%-25% among women and 5%-12% among men. Selective serotonin reuptake inhibitors (SSRIs) are the most used and the most cost-effective treatment for long-term major depressive disorder. Since the introduction of generic SSRIs, the costs of branded drugs have been questioned. The objective of this study was to assess the cost-effectiveness (€ per quality-adjusted life year [QALY]) of escitalopram (which is still covered by a patent) compared with paroxetine, sertraline, and citalopram, the patents for which have expired. Methods: A decision analytic model was adapted from the Swedish Dental and Pharmaceutical Benefits agency model to reflect current clinical practice in the treatment of depression in Italy in collaboration with an expert panel of Italian psychiatrists and health economists. The population comprised patients with a first diagnosis of major depressive disorder and receiving for the first time one of the following SSRIs: escitalopram, sertraline, paroxetine, and citalopram. The time frame used was 12 months. Efficacy and utility data for the original model were validated by our expert panel. Local data were considered for resource utilization and for treatment costs based on the Lombardy region health service perspective. Several scenario simulations, one-way sensitivity analyses, and Monte Carlo simulations were performed to test the robustness of the model. Results: The base case scenario showed that escitalopram had an incremental cost-effectiveness ratio (ICER) of €4395 and €1080 per QALY compared with sertraline and paroxetine, respectively. Escitalopram was dominant over citalopram, which was confirmed by most one-way sensitivity analyses. The escitalopram strategy gained 0.011 QALYs more than citalopram, 0.008 more than paroxetine, and around 0.007 more than sertraline. Monte Carlo simulations indicated that ICER values for escitalopram were centered around €1100 and €4400 per QALY compared with paroxetine and sertraline, respectively. Although there is no official cost-effectiveness threshold in Italy, the value of €25,000 per QALY could be acceptable. All ICER values retrieved in all analyses were lower than this threshold. Conclusion: The findings from this cost-effectiveness analysis indicate that escitalopram could be accepted as a cost-effective strategy for the Lombardy region health service compared with the other SSRIs studied. The present assessment is based on ICER values resulting from this analysis, which are lower than the thresholds proposed by health care authorities in other European Union countries. These benefits are driven by the effectiveness of escitalopram, which result in an improved health-related quality of life, a higher probability of sustained remission, and better utilization of health care resources. The study results are robust and in line with other pharmacoeconomic analyses comparing escitalopram with other SSRIs. © 2013 Mencacci et al, publisher and licensee Dove Medical Press Ltd.