Assessing social and economic impact of subcutaneous mAbs in oncology

Background: Rituximab and trastuzumab were the first monoclonal antibodies (mAbs) approved for the treatment of cancer patients. Both antibodies are administered intravenously (EV), but subcutaneous (SC) formulations have recently been developed. SC formulations proved to be as safe and effective as EV and to offer substantial benefits to the patient. Objective: The aim of this study was to provide a multidimensional assessment of the impact of rituximab and trastuzumab SC compared to the EV formulation, providing a particular focus on expected social and economic benefits for the patient. Methods: The best established HTA methods were applied to gather and organize evidence concerning the clinical, economic, organizational, social and ethical impact of SC formulations of rituximab and trastuzumab. Social aspects were investigated applying regression methods to data collected with a previous research, while the potential savings associated with the use of SC formulations were estimated by a simple economic model applying the societal perspective. Results Patients undergoing subcutaneous formulation are significantly more satisfied with their treatment experience than those treated with intravenous formulation. Subcutaneous formulation reduces patient dosing times, with a positive effect on the care provider's autonomy and productivity. Potential savings associated with the use of rituximab SC were estimated in € 4,050 per patient per year on average. For trastuzumab SC the estimated potential savings amounted to € 3,400 per patient per year, on average. Conclusion Rituximab and trastuzumab are promising treatment options significantly improving patients qol and reducing the treatment burden in terms of societal costs

Advanced-Metastatic Non-Small-Cell Lung Cancer EGFR-mutated in Italy: patient management costs and potential productivity losses:

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are established therapies for previously untreated advanced/metastatic non-small cell lung cancer (NSCLC) EGFR-mutated patients. Osimertinib, a third-generation TKI, has recently received the same first-line indication. This study aims at investigating management costs and potential productivity losses in Italy in this patient setting, given all the available therapeutic options. Two analyses were performed. The first evaluates first-line yearly management costs and potential productivity losses per patient, for each first-line treatment. The second, performed nationally and regionally, models all lines of treatments and costs over a five-year period, through different market-share scenarios – considering osimertinib adoption as new therapy in 60% of patients as the most probable one – and line-switch/mortality probabilities. Using this model, patients' total months of treatment and development/progression of brain metastases were also analyzed. The first analysis shows that first-line management costs and potential productivity losses are minimized by osimertinib (first-line yearly expenditure of €25.942, 8%-12% less than TKIs). The second analysis, based on a five-year horizon and on all therapy lines, shows that total management costs and potential productivity losses decrease by increasing the adoption of osimertinib as a first-line therapy (€7.4m cumulative lower cost with osimertinib at 60% compared to 0%). Considering the average month of therapy, where results are not affected by the length of the therapy, with osimertinib at 60% on naïve patients, monthly management costs and productivity losses are 10% lower than in the non-osimertinib scenario. In advanced, metastatic EGFR-mutated NSCLC, the use of osimertinib as the first-line treatment could reduce patient management costs and potential productivity losses

Experimental and Numerical Analysis of a Non-Newtonian Fluids Processing Pump

Abstract Centrifugal pumps are used in many applications in which non-Newtonian fluids are involved: food processing industry, pharmaceutical and oil/gas applications. In addition to pressure and temperature, the viscosity of a non-Newtonian fluid depends on the shear rate and usually is several orders of magnitude higher than water. High values of viscosity cause a derating of pump performance with respect to water. Nowadays, pumping and mixing non-Newtonian fluids is a matter of increasing interest, but there is still lack of a detailed analysis of the fluid-dynamic phenomena occurring within these machines. A specific design process should take into account these effects in order to define the proper pump geometry, able to operate with non-Newtonian fluids with specific characteristics. Only few approaches are available for correcting the pump performance based on the Hydraulic Institute method. In this work, an experimental and numerical campaign is presented for a semi–open impeller centrifugal pump elaborating non-Newtonian fluids. An on-purpose test bench was built and used to investigate the influence on pump performance of three different non-Newtonian fluids. Each pump performance test was accompanied by the rheological characterization of the fluid, in order to detect modifications of the rheological phenomena and allow a proper Computation Fluid Dynamics (CFD) modeling. The performance of the machine handling both Newtonian and non-Newtonian fluids are highlighted in relation with the internal flow field

Geological and geomorphological analysis of a complex landslides system: the case of San Martino sulla Marruccina (Abruzzo, Central Italy)

This work deals with the landslides affecting the area surrounding the village of San Martino sulla Marrucina and involving the neighboring municipalities of Casacanditella and Filetto. The geological and geomorphological settings of this area are being discussed. The enclosed maps have been realized following a multidisciplinary approach, based on morphometric, geological, and geomorphological analyses and supported by air-photo interpretation, dendrochronology, and satellite SAR interferometry (InSAR). The map is organized in four sections: orography (on the upper part), geological map (on the upper right part), main geomorphological map (in the central left part, 1:7,500 scale), and multitemporal analysis (in the lower part). The aforementioned multi-temporal assessment of landslides was performed according to the geomorphological evidence-based criteria and the past ground displacement measurements were obtained by dendrochronology and InSAR. The aim of the study is to understand the evolution in time and space of this landslide area, focusing on the corresponding kinematics

A Logical Verification Methodology for Service-Oriented Computing

We introduce a logical verification methodology for checking behavioural properties of service-oriented computing systems. Service properties are described by means of SocL, a branching-time temporal logic that we have specifically designed to express in an effective way distinctive aspects of services, such as, e.g., acceptance of a request, provision of a response, and correlation among service requests and responses. Our approach allows service properties to be expressed in such a way that they can be independent of service domains and specifications. We show an instantiation of our general methodology that uses the formal language COWS to conveniently specify services and the expressly developed software tool CMC to assist the user in the task of verifying SocL formulae over service specifications. We demonstrate feasibility and effectiveness of our methodology by means of the specification and the analysis of a case study in the automotive domain

MicroRNAs distribution in different phenotypes of Aortic Stenosis

Aortic valve stenosis (AVS) represents a cluster of different phenotypes, considering gradient and flow pattern. Circulating micro RNAs may reflect specific pathophysiological processes and could be useful biomarkers to identify disease. We assessed 80 patients (81, 76.7-84 years; 46, 57.5%females) with severe AVS. We performed bio-humoral evaluation (including circulating miRNA-1, 21, 29, 133) and 2D-echocardiography. Patients were classified according to ACC/AHA groups (D1-D3) and flow-gradient classification, considering normal/low flow, (NF/LF) and normal/high gradient, (NG/HG). Patients with reduced ejection fractionwere characterized by higher levels of miRNA1 (p = 0.003) and miRNA 133 (p = 0.03). LF condition was associated with higher levels of miRNA1 (p = 0.02) and miRNA21 (p = 0.02). Levels of miRNA21 were increased in patients with reduced Global longitudinal strain (p = 0.03). LF-HG and LF-LG showed higher levels of miRNA1 expression (p = 0.005). At one-year follow-up miRNA21 and miRNA29 levels resulted significant independent predictors of reverse remodeling and systolic function increase, respectively. Different phenotypes of AVS may express differential levels and types of miRNAs, which may retain a pathophysiological role in pro-hypertrophic and pro-fibrotic processes

Micro‑RNA‑21 (biomarker) and global longitudinal strain (functional marker) in detection of myocardial fibrotic burden in severe aortic valve stenosis: a pilot study

Aims: Myocardial fibrosis (MF) is a deleterious consequence of aortic valve stenosis (AVS). Global longitudinal strain (GLS) is a novel left ventricular (LV) functional parameter potentially useful to non-invasively estimate MF. MicroRNAs (miRNAs) are non-coding small ribonucleic acids (RNA) modulating genes function, mainly through RNA degradation. miRNA-21 is a biomarker associated with MF in pressure overload. The aim of the present study was to find an integrated algorithm for detection of MF using a combined approach with both bio- and functional markers. Methods: Thirty-six patients (75.2±8 y.o.; 63% Female) with severe AVS and preserved LV ejection fraction (EF), candidate to surgical aortic valve replacement (sAVR) were enrolled. Clinical, bio-humoral evaluation (including plasmatic miRNA-21 collected using specific tubes, PAXgene, for stabilization of peripheral RNA) and a complete echocardiographic study, including GLS and septal strain, were performed before sAVR. Twenty-eight of those patients underwent sAVR and, in 23 of them, an inter-ventricular septum biopsy was performed. Tissues were fixed in formalin and embedded in paraffin. Sections were stained with Hematoxylin and Eosin for histological evaluation and with histochemical Masson trichrome for collagen fibers. The different components were calculated and expressed as micrometers2. To evaluate tissue miRNA components, sections2-μm thick were cut using a microtome blade for each slide. Regression analysis was performed to test association between dependent variable and various predictors included in the model. Results: Despite a preserved EF (66±11%), patients presented altered myocardial deformation parameters (GLS -14,02±3.8%; septal longitudinal strain, SSL -9.63±2.9%; septal longitudinal strain rate, SL-Sr -0.58±0.17 1/s; Septal Longitudinal early-diastolic strain rate, SL-SrE 0.62±0.32 1/s). The extent of MF showed an inverse association with both GLS and septal longitudinal deformation indices (GLS: R2=0.30; p=0.02; SSL: R2=0.36; p=0.01; SL-Sr: R2=0.39; p<0.001; SL-SrE: R2=0.35; p=0.001). miRNA-21 was mainly expressed in fibrous tissue (p<0.0001). A significant association between MF and plasmatic miRNA-21, alone and weighted for measures of structural (LVMi R2=0.50; p=0.0005) and functional (SSL R2=0.35; p=0.006) remodeling, was found. Conclusions: In AVS, MF is associated with alterations of regional and global strain. Plasmatic miRNA-21 is directly related to MF and associated with LV structural and functional impairment. © 2016 The Author(s)

Metabolic-imaging of human glioblastoma live tumors: A new precision-medicine approach to predict tumor treatment response early

Glioblastoma (GB) is the most severe form of brain cancer, with a 12-15 month median survival. Surgical resection, temozolomide (TMZ) treatment, and radiotherapy remain the primary therapeutic options for GB, and no new therapies have been introduced in recent years. This therapeutic standstill is primarily due to preclinical approaches that do not fully respect the complexity of GB cell biology and fail to test efficiently anti-cancer treatments. Therefore, better treatment screening approaches are needed. In this study, we have developed a novel functional precision medicine approach to test the response to anticancer treatments in organoids derived from the resected tumors of glioblastoma patients