Economic consequences of investing in anti-HCV antiviral treatment from the Italian NHS perspective : a real-world-based analysis of PITER data

OBJECTIVE: We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy. METHODS: A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered. RESULTS: The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively. CONCLUSIONS: This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV

Fracture of a polyethylene post in a 9-year-old posterior-stabilized knee prosthesis: light microscopy and SEM evaluation

Objective Aim of this study is to evaluate the surface of the TKA polyethylene liner, harvested after the breakage of the post nine years after the implant in a 63 years old female (BMI 39) after an hyperextension trauma. Methods During the revision we harvested sample of the periprosthetic tissue which was prepared for the light microscopy evaluation. The samples were stained using both haematoxylineosin and Von Kossa. The PE liner was prepared for the Scanning Electron Microscopy. Results The SEM evaluation revealed two different damage patterns considering the medial part and the lateral aspect of the sample. The medial part presented a fracture line laminated in front and smooth behind and with the tear lines with a medio-lateral and anterior posterior orientation. The lateral part presented a sharp fracture line that ends anteriorly with a laminated tear paralleled to the anterior edge of the polyethylene insert, and which implies that this area could be the terminal failure area of the fractured post. The medial part of the fracture edge appears to be smooth and with a different orientation of the fracture lines. Conclusions These features could be explained with a \u2018\u2018two stage\u2019\u2019 rupture of the polyethylene post. This could have been caused by a non-optimal ligamentous balance that weakened the post, which was finally broken by a postero-anterior stress

Development of various forms of lung injury with increasing tidal volume in normal rats

Background: Mechanical ventilation (MV) with large tidal volumes (VT) causes lung edema, mechanical alterations, tissue lesions, and release of inflammatory markers. Objective: The aim of the present study is to explore the dependence of these events on tissue strain-stress. Methods: Sixty-three, normal, open-chest, normal rats were ventilated for 2-4 hours with VT from 7.5 (baseline ventilation) to 39.5ml\uf0d7kg-1 and PEEP ~2.5cmH2. Arterial blood gasses and mean pressure, and lung mechanics were measured during baseline ventilation before and after test ventilation, when cytokine, von Willebrand Factor (vWF), and albumin concentration in serum and broncho-alveolar lavage fluid (BALF), lung wet-to-dry ratio (W/D), and histologic injury scores were assessed. Main results: Elevation of W/D and serum vWF and cytokine concentration occurred with VT>25ml\uf0d7kg-1 and peak inflation pressure (Ppeak) >25cmH2O, whereas with VT>30ml\uf0d7kg-1 and Ppeak>30cmH2O, cytokine and albumin concentration increased also in BALF, arterial oxygen tension decreased, and lung mechanics and histology deteriorated, while W/D and serum vWF and cytokine concentration increased further. Conclusions: In normal rats, lung injury occurs once a definite volume and/or pressure threshold is overcome. Microvascular stress-strain failure leading to interstitial edema is the initial manifestation of injurious MV, as shown by elevated vWF and cytokine levels in serum only. Failure of the epithelial barrier with alveolar flooding occurs only at higher stress-strain levels, with inflammatory reaction, mechanical and histologic damage proportional to the concomitant edema formation

Surgery in patients with testicular MGCT: compliance to surgical guidelines and results in the Italian Cooperative Study

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