375 research outputs found
Analisi agli elementi distinti e possibile evoluzione di un fronte di cava in calcari fratturati e carsificati.
No full textApixaban, Dabigatran, and Rivaroxaban Versus Warfarin for Stroke Prevention in Non-Valvular Atrial Fibrillation: A Cost-Effectiveness Analysis
No full textBackground and objective
Non-valvular atrial fibrillation (NVAF) increases the risk of systemic thromboembolic events; therefore, anticoagulant treatment with vitamin K antagonists is widely prescribed. Recently, new oral anticoagulants (NOAs) directly inhibiting thrombin (dabigatran) or factor Xa (rivaroxaban and apixaban) demonstrated their non-inferiority with respect to warfarin in reducing the thromboembolic risk. The aim of this study was to estimate the cost effectiveness of NOAs in an Italian setting.
Methods
A Markov decision model including ten health states and death was developed, and a 3-month Markov cycle and lifetime horizon were adopted. Transition probabilities and quality of life were estimated from three randomized trials and from additional reports in the literature. Analysis was performed in the context of the Italian National Health System. First- and second-order sensitivity analyses were made to test the robustness of the results. The mean European cost of dabigatran (€2.58/day) was assigned to each NOA.
Results
The incremental cost-utility ratio was below €25,000/quality-adjusted life-year (QALY) gained for each NOA and each CHADS2 level, but differences among drugs were found. This result was sensitive to the time in (warfarin) therapeutic range and time horizon.
Conclusions
Our analysis suggests that NOAs are a cost-effective treatment for the prevention of stroke in patients with NVAF in the Italian healthcare setting
Comparative Clinical Value of Pharmacologic Therapies for B-Cell Chronic Lymphocytic Leukemia: An Umbrella Analysis
No full textSeveral new drugs are progressively improving the life span of patients with B-cell chronic lymphocytic leukemia (CLL). However, the rapidly evolving standard of care precludes robust assessments of the incremental clinical value of further innovative drugs. Therefore, we systematically reviewed comparative evidence on newly authorized CLL drugs, as reported by standard and network meta-analyses (MA) published since 2016. Overall, 17 MAs addressed the relative survival or safety of naïve and/or refractory/relapsed (R/R) CLL patients. In R/R patients, therapies including BTK- and BCL2-inhibitors reported progression free survival (PFS) hazard ratios ranging from 0.08 to 0.24 (versus chemotherapy) and a significant advantage in overall survival (OS). In naïve patients, the PFS hazard ratios associated with four recent chemo-free therapies (obinutuzumab- and/or acalabrutinib-based) ranged from 0.11 to 0.61 versus current standard treatments (STs), without a significant OS advantage. Ten MAs addressed the risk of cardiovascular, bleeding, and infective events associated with BTK inhibitors, with some reporting a different relative safety in naïve and R/R patients. In conclusion, last-generation therapies for CLL consistently increase PFS, but not OS, and minimally decrease safety, as compared with STs. Based on available evidence, the patient-customized adoption of new therapies, rather than universal recommendations, seems desirable in CLL patients
Edoxaban versus warfarin for stroke prevention in non-valvular atrial fibrillation: a cost-effectiveness analysis
No full textEdoxaban, an oral direct factor Xa inhibitor, has been found non-inferior to warfarin for preventing stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF), with a lower rate of intracranial bleeding. The aim of our investigation was to assess the cost-effectiveness of edoxaban versus warfarin from the perspective of the Italian health-care system. A Markov decision model was used to evaluate lifetime cost and quality-adjusted life expectancy of NVAF patients treated with warfarin or edoxaban. Transition probabilities were obtained from the ENGAGE AF-TIMI 48 trial, cost estimates were based on Italian prices and tariffs, utilities were obtained from the literature. One-way and second-order sensitivity analyses were performed. In the base case, lifetime costs were €18,658 for edoxaban and €14,060 for warfarin. Discounted quality-adjusted survival was 9.022 years for edoxaban and 8.425 years for warfarin, leading to an incremental cost-utility ratio of €7,713 per quality-adjusted life year (QALY) gained. Results were sensitive to time horizon, time in therapeutic range of warfarin and to the relative impact of warfarin versus edoxaban therapy onto quality of life. Probabilistic sensitivity analysis showed edoxaban to be cost-effective versus warfarin in 92.3 % of the simulations at a willingness-to-pay threshold of €25,000 per QALY. In conclusion, edoxaban proved to be a cost-effective alternative to warfarin in patients with moderate-to-high-risk NVAF
ROCK SLOPE ANALYSIS ON THE COMPLEX LIVORNO COASTAL CLIFF (TUSCANY, ITALY)
No full textThe landscape of the south coast of Livorno city (Tuscany, Italy) is
characterized by sandstone headlands and sandy pocket beaches affected
by serious stability problems. Lithological features and physical-chemical
processes involve many slope failures concerning the sandstone cliff and
extending all over the cliff height; these failures often threaten people
and facilities. The most prominent positive relief landform is structurally
controlled by three main closely spaced joint sets. The presence of leaning
and collapsed rock blocks suggests that erosion and mass wasting
maintain the cliff steepness and elevate risk conditions. The sandstone
mechanical properties and discontinuity pattern have been investigated
in order to determine the response of the rock mass to subaerial and marine
stresses. The sandstone outcrops were characterized according to the
Rock Mass Rating (Bieniawski, 1989) and the Slope Mass Rating (Romana,
1985; 1993). Such data has been reported in a GIS system in order
to determine the landslide susceptibility of the cliff. Some numerical
modelling, with a code at Distinct Element Method model, were carried
out to evaluate stresses and displacement distribution near the free surface
of a steep slope face, as a function of steepness, dip direction and
rock mass quality. Then some fall simulations were carried out, to make a
back analysis of previous events and to obtain a more general outline of
possible movements. The results showed that rock mechanics and computer
modelling can be effective tools in predicting the rock-mass stability,
determining the mechanism by which blocks fall from steep slopes
and their possible trajectorie
FRONTLINE THERAPY FOR NON-TRANSPLANT ELIGIBLE MULTIPLE MYELOMA: A CRITICAL APPRAISAL OF PUBLISHED NETWORK META-ANALYSES
No full textNewly diagnosed multiple myeloma (MM) who are transplant ineligible (NTE NDMM) are usually treated with multiple-drug combinations including proteasome inhibitors, immunomodulatory drugs and alkylating agents. Recently approved combo therapies including anti-CD38 monoclonal agents and/or lenalidomide improve progression-free survival (PFS) as compared with one of the standard treatments. We thus aimed at assessing the relative efficacy of novel daratumumab-based and lenalidomide based triplets/quadruplets as compared with overall standard treatments for NTE NDMM, namely Rd and VMP. Network meta-analyses (NMA) are accepted evidence-based tools for conducting indirect comparisons among treatments, however, the scientific community is still skeptical regarding their robustness. We, therefore conducted an umbrella review: fully published NMAs were retrieved by standard searches (EBMASE, Cochrane Library, MEDLINE/PubMed) and appraised by AMSTAR-2 and ROBIS tools. Three indirect comparisons of PFS were targeted: 1) VRD versus VMP, 2) DaraRd versus VMP, 3) DaraVMP versus Rd. Overall 17 NMA addressing NDMM were published since Jan 2017: 6 fully published ones including both daratumumab- and lenalidomide-based novel treatments were appraised. The overall quality of the NMAs was poor to moderate according to AMSTAR-2 and ROBIS. Each NMA analyzed 6 to 27 trials and 2 ones were company sponsored. 1) VRD was compared to VMP by 3 moderate-quality NMAs, which consistently reported a significant amelioration of PFS or higher SUCRA of VRD, while OS-HR was not conclusive. 2) DaraRd was compared to VMP by 4 NMAs and the pooled PFSHR ranged from 0.39 to 0.61. A significant amelioration of OS was also reported by the unique NMA assessing this endpoint. 3) DaraVMP was compared versus Rd by 4 NMAs. Pooled HR ranged from 0.35 to 0.71, which was statistically significant in two ones. DaraVMP achieved the highest SUCRA (0.960) in the latest and largest NMA (Giri et al 2020). Only one NMA compared OS of the two regimens and did not report a significant advantage of DaraVMP. In conclusion, Dara-VMP, VRD and Dara-Rd show mostly a favorable PFS profile as both directly and indirectly compared with standard frontline treatments for NTE NDMM. NMAs are valuable evidence-based tools, however, their quality needs to be appraised before using their result to support clinical recommendations. Future NMAs are expected to incorporate also safety endpoints in order to allow benefit to risk assessments
Slope stability modeling of a sandstone cliff south of Livorno (Tuscany, Italy).
No full textThe landscape of the coast south of the town of Livorno (Tuscany, Italy) is characterized by sandstone headlands and sandy pocket beaches. Lithological features and physical-chemical processes favour many slope failures (mainly rock slides and rock falls) involving the sandstone cliffs and extending all over the cliff height; these failures often threaten people and facilities. The most prominent positive relief landform is structurally controlled by three main, closely spaced orthogonal joint sets. The presence of leaning and collapsed rock
blocks suggests that continuous sea erosion and mass wasting maintain the cliff slopes steepness and risk conditions. The sandstone mechanical properties and fracture pattern have been investigated in order to determine the response of the rock mass to subaerial and marine stress. Hardness and weathering of the rocks were assessed using a Schmidt hammer and the Point Load Test, and statistical analysis was undertaken to remove outlying values. The sandstone outcrops were characterized according to the Bieniawski’s RMR and Romana’s Slope Mass Rating. Such data have been reported in a GIS system in order to determine the landslide susceptibility of the cliff. A series of stability analyses, with a Distinct Element Method (DEM) model, were carried out to evaluate stress and displacement distribution near the free surface of a vertical slope face, as a function of steepness, dip direction and rock mass quality. The results showed that assessing block geometry could provide an effective tool in predicting the rock-mass stability, determining the mechanism by which blocks fail from a vertical slope, and the consequent repetitive slope failures through time
Graphical models of marginal independencies for categorical variables
No full textUndirected graphical models for categorical data represent a set of conditional independencies
between pairs of variables given all the remaining variables. These models can be fitted by
classical log-linear models. In this paper we discuss instead models of marginal independence between
categorical variables. These models have a graphical representation as bi-directed graphs called
also covariance graphs (Cox and Wermuth, 1993; Richardson, 2003). We discuss a parameterization
of marginal independence models for discrete variables based on the marginal log-linear models by
Bergsma and Rudas (2002). This allows the encoding of any marginal independence model for a set of
categorical variables associated with a given bi-directed graph. We develop an algorithm for maximum
likelihood estimation of bi-directed graph models presenting a simple illustration
Cancer-related fatigue in Italian cancer patients: validation of the Italian version of the Brief Fatigue Inventory (BFI)
No full textCancer-related fatigue (CRF) is one of the most common symptoms experienced by cancer patients (CPs). The Brief Fatigue Inventory (BFI) is a reliable instrument to assess CRF in CPs. The aim of this study was to evaluate the psychometric properties of the Italian version of the BFI (BFI-I)
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