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Sofia Silvola,1,2 Umberto Restelli,1,3 Marzia Bonfanti,1 Davide Croce1 1LIUC - Università Cattaneo, Castellanza, VA, Italy; 2Department of Public Health Medicine, School of Health System & Public Health, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa; 3School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaCorrespondence: Sofia Silvola, Tel +39 0331 572 509, Email silvola.sofia@gmail.comAbstract: Service design and in particular co-design are approaches able to align with the need of healthcare contexts of value-based and patient-centered processing through a participatory design of services. The purpose of this study is to identify the characteristics of co-design and its applicability to the reengineering of healthcare services, as well as to detect the peculiarities of the application of this approach in different geographical contexts. The methodology applied for the review, Systematic Literature Network Analysis (SLNA), combines qualitative and quantitative perspectives. In detail, the analysis applied the paper citation networks and the co-word network analysis to detect the main research trends over time and to identify the most relevant publications. The results of the analysis highlight the backbone of literature on the application of co-design in healthcare as well as the advantages and the critical factors of the approach. Three main literature streams emerged concerning the integration of the approach at meso and micro level, the implementation of co-design at mega and macro level, and the impacts on non-clinical related outcomes. Moreover, the findings underline differences in co-design in terms of impacts and success factors in developed countries and economies in transition or developing countries. The analysis shows the potentially added value of the application of a participatory approach to the design and redesign of healthcare services both at different levels of the healthcare organization and in the contexts of developed countries and economies in transition or developing countries. The evidence also highlights potentialities and critical success factors of the application of co-design in healthcare services redesign.Keywords: co-creation, co-production, systematic literature network analysis, healthcare services

Umberto Restelli,1,2 Giuliano Rizzardini,3,4 Andrea Antinori,5 Adriano Lazzarin,6 Marzia Bonfanti,1 Paolo Bonfanti,7 Davide Croce1,2 1Centre for Research on Health Economics, Social and Health Care Management, LIUC – Università Cattaneo, Castellanza, Varese, Italy; 2School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 3First and Second Divisions of Infectious Diseases, “Luigi Sacco” Hospital, Milan, Italy; 4School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 5National Institute for Infectious Diseases “L Spallanzani”, Rome, 6Department of Infectious Diseases, San Raffaele Scientific Institute, 7Department of Infectious and Tropical Diseases, A Manzoni Hospital, Lecco, Italy Background: In January 2014, the European Medicines Agency issued a marketing authorization for dolutegravir (DTG), a second-generation integrase strand transfer inhibitor for HIV treatment. The study aimed at determining the incremental cost-effectiveness ratio (ICER) of the use of DTG+backbone compared with raltegravir (RAL)+backbone, darunavir (DRV)+ritonavir(r)+backbone and efavirenz/tenofovir/emtricitabine (EFV/TDF/FTC) in HIV-positive treatment-naïve patients and compared with RAL+backbone in treatment-experienced patients, from the Italian National Health Service’s point of view.Materials and methods: A published Monte Carlo Individual Simulation Model (ARAMIS-DTG model) was used to perform the analysis. Patients pass through mutually exclusive health states (defined in terms of diagnosis of HIV with or without opportunistic infections [OIs] and cardiovascular disease [CVD]) and successive lines of therapy. The model considers costs (2014) and quality of life per monthly cycle in a lifetime horizon. Costs and quality-adjusted life years (QALYs) are dependent on OI, CVD, AIDS events, adverse events and antiretroviral therapies.Results: In treatment-naïve patients, DTG dominates RAL; compared with DRV/r, the ICER obtained is of 38,586 €/QALY (6,170 €/QALY in patients with high viral load) and over EFV/TDF/FTC, DTG generates an ICER of 33,664 €/QALY. In treatment-experienced patients, DTG compared to RAL leads to an ICER of 12,074 €/QALY.Conclusion: The use of DTG+backbone may be cost effective in treatment-naïve and treatment-experienced patients compared with RAL+backbone and in treatment-naïve patients compared with DRV/r+backbone and EFV/TDF/FTC considering a threshold of 40,000 €/QALY. Keywords: antiretroviral therapy, costs, economic evaluation, cost-utility analysis

Davide Croce,1,2 Marzia Bonfanti,1 Umberto Restelli1,2 1Center for Research on Health Economics, Social and Health Care Management, Università Cattaneo, Castellanza, Italy; 2School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa Background: Hepatitis C virus (HCV) affects an estimated number of people between 130 million and 210 million worldwide. In the next few years, the Italian National Health Service will face a growing trend of patients requiring HCV antiviral treatments. The aim of the analysis was to estimate the time horizon in which it would be possible to treat HCV-infected patients and the related direct medical costs (antiviral treatment and monitoring activities) from the Italian National Health Service point of view.Methodology: In order to estimate the number of HCV-infected patients in Italy, we considered a top-down (considering published data) and a bottom-up approach. The number of years needed for treatment and related direct costs were estimated through the development of a static deterministic model.Results: The estimated number of HCV-infected patients in Italy varies from 2.7 (estimated through a top-down approach) to 0.6 million (estimated through a bottom-up approach) and 0.3 million (measured through a bottom-up approach). Considering the last two scenarios and the use of interferon-free therapies for 50,000 patients per year, treatment for HCV-infected patients could be at a cost of €13.7 billion and €7.0 billion by 2030 and 2023, respectively.Conclusion: The treatment for HCV-infected patients in Italy is a challenging target for the financial implications of patient care. HCV infection could be controlled or eliminated in a 10- to 15-year time horizon. The cost of treatment can hardly be dealt with using the traditional economic tools but should be faced through multiyear investments, as health benefits are expected in the long period. National Health Service stakeholders (industry, government, insurance, and also patients) will have to identify suitable financial instruments to face the new expenditure required. Keywords: sustainability, financial disease scenario, budget impact model

Umberto Restelli,1,2 Massimo Andreoni,3 Andrea Antinori,4 Marzia Bonfanti,2 Giovanni Di Perri,5 Massimo Galli,6 Adriano Lazzarin,7 Giuliano Rizzardini,8,9 Davide Croce1,2 1Department of Community Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 2Centro di Ricerca in Economia e Management in Sanità e nel Sociale (CREMS), Università Carlo Cattaneo – LIUC, Castellanza (VA), Italy; 3Clinical Infectious Diseases, Tor Vergata University (PTV), Rome, Italy; 4Clinical Department, National Institute for Infectious Diseases "L. Spallanzani," Rome, Italy; 5Department of Medical Sciences, Infectious Diseases, Amedeo di Savoia Hospital, Turin, Italy; 6Third Division of Infectious Diseases, "Luigi Sacco" Hospital, Milan, Italy; 7Department of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy; 8First and Second Divisions of Infectious Diseases, "Luigi Sacco" Hospital, Milan, Italy; 9School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa Background: Deintensification and less drug regimen (LDR) antiretroviral therapy (ART) strategies have proved to be effective in terms of maintaining viral suppression in human immunodeficiency virus (HIV)-positive patients, increasing tolerability, and reducing toxicity of antiretroviral drugs administered to patients. However, the economic impact of these strategies have not been widely investigated. The aim of the study is to evaluate the economic impact that ART LDR could have on the Italian National Health Service (INHS) budget. Methods: A budget impact model was structured to assess the potential savings for the INHS by the use of ART LDR for HIV-positive patients with a 3 year perspective. Data concerning ART cost, patient distribution within different ARTs, and probabilities for patients to change ART on a yearly basis were collected within four Italian infectious diseases departments, providing ART to 13.7% of the total number of patients receiving ART in Italy. Results: The LDR investigated (protease inhibitor-based dual and monotherapies) led to savings for the hospitals involved when compared to the "do nothing" scenario on a 3 year basis, between 6.7% (23.11 million €) and 12.8% (44.32 million €) of the total ART expenditures. The mean yearly cost per patient is reduced from 9,875 € in the do nothing scenario to a range between 9,218 € and 8,615 €. The use of these strategies within the four departments involved would have led to a reduction of ART expenditures for the INHS of between 1.1% and 2.1% in 3 years. Conclusion: ART LDR simplification would have a significant impact in the reduction of ART-related costs within the hospitals involved in the study. These strategies could therefore be addressed as a sustainable answer to the public financing reduction observed within the INHS in the last year, allowing therapies to be dispensed without affecting the quality of the services provided. Keywords: antiretroviral therapy, Italy, budget impact model, monotherapy, dual therapy, cost

We investigated binding of hydrogen atoms to small polycyclic aromatic hydrocarbons (PAHs)-i.e., graphene dots with hydrogen-terminated edges-using density functional theory and correlated wavefunction techniques. We considered a number of PAHs with three to seven hexagonal rings and computed binding energies for most of the symmetry unique sites, along with the minimum energy paths for significant cases. The chosen PAHs are small enough to not present radical character at their edges, yet show a clear preference for adsorption at the edge sites which can be attributed to electronic effects. We show how the results, as obtained at different levels of theory, can be rationalized in detail with the help of a few simple concepts derivable from a tight-binding model of the π electrons. [ABSTRACT FROM AUTHOR]

We report an experimental study on the recombination kinetics of single strain-free GaAs quantum dots (QDs) grown by modified droplet epitaxy. The different bands composing the single quantum dot emission line at high temperature show identical dynamics, proving the common origin of all contributions. Our results thus agree with the interpretation of the broad pedestal band appearing when increasing the temperature as originated from the phonon replica. Finally, the relative weight of the phonon replicas depends both on temperature and on the QD size, in agreement with the theoretical predictions. [ABSTRACT FROM AUTHOR]

A detailed spectroscopic and morphological study of GaAs epitaxial layers grown by molecular beam epitaxy on Ge buffer layers deposited by low energy plasma enhanced chemical vapor deposition on Si is presented. The aim is to understand the nature of thermal strain relaxation induced by crack formation in the epilayers. The comparison of the experimental data on the spatial strain relaxation pattern with the theoretical prediction from a purely elastic model indicates that strain relaxation around cracks arises from two contributions. At short distances the main contribution is essentially plastic, due to the presence of extended defects. At large distances, on the contrary, elastic relaxation seems to dominate. It is also shown that GaAs grown on Ge/Si substrates is in a state of metastable strain as a consequence of the fact that cracks relax the thermal tensile strain only locally. [ABSTRACT FROM AUTHOR]

Tissue equivalent proportional counter (TEPC) is the most accurate device for measuring the microdosimetric properties of a particle beam, nevertheless no detailed information on the track structure of the impinging particles can be obtained, since the lower operation limit of common TEPCs is ~0.3 μm. On the other hand, the pattern of particle interactions at the nanometer level is measured by only three different nanodosimeters worldwide: practical instruments are not yet available. In order to partially fill the gap between microdosimetry and track-nanodosimetry, a low-pressure avalanche-confinement TEPC was recently designed and constructed for simulating tissue-equivalent sites down to the nanometric region. The present article aims at describing the response of this newly developed TEPC in the range 0.3 μm–25 nm against a fast neutron field from a 241Am–Be source and a quasi-monoenergetic neutron beam. The experimental results are in good agreement with Monte Carlo simulations carried out with the FLUKA code. [ABSTRACT FROM AUTHOR]