cost per response remission in biologics available in italy for the treatment of tnf α inhibitors naive patients with ulcerative colitis

Objective: This study compares the cost of a sustained response or remission (at 52 weeks' follow-up) across biologics approved in Italy for the treatment of moderately to severely active ulcerative colitis (UC), specifically among anti-TNF-α-naïve patients. The analysis is from the perspective of the national healthcare provider (SSN) for one year of treatment. Methods: Efficacy data about the induction of response/remission probabilities at 52 weeks and the number needed to treat (NNT) were derived from a network meta-analysis of randomized controlled clinical trials of the following drugs: infliximab (originator and biosimilar), adalimumab, golimumab and vedolizumab. It included the acquisition and administration costs of biologics, based on an activity-based costing analysis performed in 3 Italian centers of excellence for UC treatment. Results: The costs per patient in sustained response at 52 weeks were, in increasing order: vedolizumab €47,772 (95% CI €29,869 - €101,055), biosimilar infliximab €48,657 (95% CI €31,488 - €95,523), golimumab (100 mg every 4 weeks at maintenance) €57,940 (95% CI €38,00 - €106,206), golimumab (50 mg every 4 weeks at maintenance) €62,504 (95% CI €39,976 - €120,477), adalimumab €101,181 (95% CI €49,635 - €422,334). The costs per patient in sustained remission at 52 weeks were: vedolizumab €86,220 (95% CI €47,015 - €206,652), biosimilar infliximab €92,562 (95% CI €52,954 - €203,619). Conclusions: In patients with moderate to severe UC not previously treated with TNF-α inhibitors, treatment needed with vedolizumab to obtain a response or remission at 52 weeks of follow-up is less costly to the SSN compared with the other UC-approved biologics available in Italy

Indagine tramite questionari sull'influenza di stress ed esposizioni ambientali nell'insorgenza della Miastenia Gravis

La Miastenia Gravis è una patologia autoimmune che colpisce la giunzione neuromuscolare. In questa malattia il normale meccanismo di trasmissione degli impulsi dai nervi ai muscoli risulta alterato, provoca debolezza e affaticamento muscolare, facendo perdere progressivamente tono e forza. Si tratta di una patologia relativamente rara che colpisce entrambi i sessi e tutte le etnie. In molti casi è difficile da diagnosticare ed è necessario un trattamento personalizzato, a causa della sintomatologia poco specifica e del coinvolgimento di diversi autoanticorpi che influiscono sullo sviluppo di timomi o iperplasia timica. La Miastenia Gravis è una malattia multifattoriale, dovuta all’interazione tra fattori genetici e ambientali; ad oggi sono stati identificati polimorfismi genici correlati sia alla Miastenia Gravis che ad altre patologie autoimmuni, indizi patogenetici specifici della malattia potrebbero essere forniti dal gene CHRNA1, tuttavia si ipotizza che tra le cause scatenanti vi siano stress ed agenti tossici. L’obiettivo di questa tesi è di indagare fattori ambientali e variabili psicologiche legate alle stress coinvolti nell’insorgenza della Miastenia Gravis. Attraverso l’utilizzo di questionari sono state indagate diverse variabili, tra cui: esposizione ambientale, familiarità e associazione con altre patologie autoimmuni, somministrazione di vaccini, e fattori di rischio prenatali. La dimensione dello stress è stata studiata mediante i seguenti questionari: COPE-NVI, STAI, SRRS. Sono stati confrontati pazienti affetti da Miastenia Gravis con un gruppo di controllo costituito da pazienti sani, il presente studio non conferma le ipotesi formulate relativamente all’implicazione dell’ambiente sull’insorgenza della malattia, tuttavia sono stati ottenuti dati significativi relativamente ad eventi stressanti vissuti, strategie di coping e livello ansia. Dallo studio emerge che i soggetti più a rischio di sviluppare una malattia da adattamento appartenengono al gruppo di controllo (p-value<0,01), nei pazienti si osserva però maggiore tendenza all’utilizzo di strategie di coping non correlate con il benessere (p-value<0,01) e livelli superiori di ansia di tratto (p-value<0,05). Confrontando i pazienti non affetti da timoma con coloro che hanno sviluppato patologia timica si osservano differenze significative relativamente all’utilizzo di strategie di coping e livelli di ansia. Oltre a livelli di ansia più elevati (p-value<0,01), i soggetti affetti da tumore al timo tendono a mettere in atto strategie di coping disadattive più frequentemente rispetto agli altri pazienti (p-value<0,01)

A GIS-based assessment of the Byzantine water supply system of Constantinople

Despite the extensive archaeological surveys carried out in the last decades, little attention has been paid to one of the longest water supply systems of ancient times - the Byzantine water infrastructure which fed Constantinople from the mid-late fourth century AD. This work uses modern satellite terrain data and Global Positioning System (GPS) data to assess this system and provide an improved description of its route, total length and gradient profile. 44 validated GPS Control Points were correlated with ASTER GDEM V2 digital satellite data and archaeological information in a Geographic Information System (GIS) environment. We concluded that the total length of the water supply system was 426 km, and possibly even 565 km if the fifth-century aqueduct continued in parallel all the way to Constantinople rather than merging with the fourth-century aqueduct. The gradient of the channels varied across their length, being steepest near the spring sources, with gradient mostly in the region of 5 m/km, and flattest at around 0.4 m/km in the most downstream section nearest the City. This reconstruction of the gradient profile provides valuable insight into the physical characteristics of the system, allowing future study of its hydraulic function

Building renovation : Which kind of guidelines could be proposed for policy makers and professional owners?

IEA IBC Annex 56 methodology provides the basis for the assessment and evaluation of energy related renovation options of residential building stock, first and foremost with respect to cost, energy use and carbon emissions. Furthermore, it allows also for a broader approach going beyond cost effective reduction of carbon emissions and energy use by taking into account co-benefits achieved in a renovation process. Besides impact indicators for primary energy use, carbon emissions and costs it also provides a methodological framework for integrating at least embodied energy use for renovation measures as part of a lifecycle impact assessment. The methodology and resulting fundamentals for renovation standards have to be applicable to different climatic and country specific situations. The Guideline for policy makers proposed by the Annex 56 gives useful information and suggestions to the drafting of legislative and administrative measures, at the national or local level, for reducing the amount of energy consumption and greenhouse gas emissions in renovation of residential buildings. The reachable saving targets must be defined in agreement with the actors in the energy market, as the owners and / or the managers of buildings, but policy makers must be aware of their responsibility in defining cost effective levels for nearly zero energy or emissions building renovation, using a life cycle perspective, and the relevance of preparing adequate financial packages to support ambitious levels for building renovation. Furthermore, the Guideline for professional owners shall report outlines key drivers for building retrofit and use and the resulting impacts on energy consumption. This Guideline shall describe building and energy efficiency trends specific to the residential building sectors

Repurposing Tempeh Fermentation: a Promising Protein Source Using Food Residues and Edible Filamentous Fungi

Brewers' spent grains (BSG) are the main by-product of the brewery industry, accounting for more than 80 % of total produced by-products. Although this matrix is primarily composed of hemicellulose, cellulose, protein and lignin, the current end-of-life scenario for BSG is as livestock feed. In the present study, a valorisation approach for BSG that uses an edible fungus (Rhizopus oligosporus) in solid state fermentations (SSF) is proposed. First, a microbiological characterization is performed, to shed light on the indigenous microorganisms that are present in the BSG matrix. Then, an appropriate technology approach is used for the SSF that can be conducted both at laboratory and household levels. In the SSF experiments, different temperature (30-35 °C), mass of BSG substrate, inoculum ratio (10 and 15 % v/m) and drilling patters for the aeration of the systems are investigated. The fermentation products were characterized by preparing homogenized samples; it was registered an increase in protein content (5-64%), a slight acidification (ΔpH=0.1-1.2), a decrease of °Brix and the loss of organic matter (and water). The formation of the tempeh cakes was variable, and the differences are analyzed in terms of the operational parameters of each studied batch

Measurements of Protein Content in Aqueous and Alkaline Extracts from Brewer's Spent Grains (bsg): Insights Into the Extraction Kinetics and Energy Consumption

The brewers’ spent grain (BSG) is a rich biomass matrix containing several compounds of interest that require urgent and suitable valorisation strategies, due to its high production volume in the brewing industry. Among the most widespread approaches is the preparation of extracts, targeting particular compounds or soluble and/or insoluble fractions, after operating pre-treatment processes. In the present study, extraction experiments are carried out with fresh untreated BSG, under very gentle extraction conditions (room temperature and moderate agitation, in the 0-5 h interval), and using different solvents: deionized water, 0.1 M NaOH and 0.5 M NaOH in a 1:5 m/v solid-to-solvent ratio. The extraction dynamics were followed by monitoring the dry matter (DM) content obtained in the extracts after a centrifugation step. The protein content is estimated in each case by means of two different methods: direct measurements of absorbance at 280 nm (using bovine serum albumin, BSA, and commercial whey protein isolate as standards) as well as using the Bradford colorimetric method and BSA standard; the consistency of these measurements is contrasted against the DM values. The apparent extraction kinetics were studied, using a saturation model; the coefficients and their range of uncertainty were obtained. Extraction efficiencies in the range 14.24%-53.60% gDM ext/gDM BSG are achieved, which correspond to extraction yields of 38.88-150.09 gDM ext/kg fresh BSG. In addition, the energy footprint of the process is estimated at laboratory scale

Thoracoscopic Approach for Congenital Diaphragmatic Hernia: A Useful Tool in Diagnosis and Treatment of Unexpected Associated Lung Lesion

We report the case of a neonate affected by prenatally diagnosed congenital diaphragmatic hernia (CDH), treated by thoracoscopy. During the procedure, we detected an associated extralobar pulmonary sequestration (EPS), which was preoperatively undiagnosed, and we removed it. EPS has been shown to be associated with CDH in up to 15 to 40% of cases. A possible explanation hypothesized is that pulmonary sequestration, which develops at 4 to 5 weeks of gestation, can disturb the fusion of the diaphragm and closure of the pleuroperitoneal canal. The thoracoscopic approach permitted us to identify the thoracic EPS that probably would have been otherwise missed

Rational-approximation-based model order reduction of Helmholtz frequency response problems with adaptive finite element snapshots

We introduce several spatially adaptive model order reduction approaches tailored to non-coercive elliptic boundary value problems, specifically, parametric-in-frequency Helmholtz problems. The offline information is computed by means of adaptive finite elements, so that each snapshot lives in a different discrete space that resolves the local singularities of the analytical solution and is adjusted to the considered frequency value. A rational surrogate is then assembled adopting either a least squares or an interpolatory approach, yielding a function-valued version of the standard rational interpolation method (V-SRI) and the minimal rational interpolation method (MRI). In the context of building an approximation for linear or quadratic functionals of the Helmholtz solution, we perform several numerical experiments to compare the proposed methodologies. Our simulations show that, for interior resonant problems (whose singularities are encoded by poles on the V-SRI and MRI work comparably well. Instead, when dealing with exterior scattering problems, whose frequency response is mostly smooth, the V-SRI method seems to be the best performing one