How Are Medium-Sized Cities Implementing Their Smart City Governance? Experiences from the Emilia-Romagna Region

Within the smart city debate, this paper aims to reflect on whether and how medium-sized Italian cities are organizing their smart transition technically as well as administratively. The smart city concept was developed in the 1990s when major European cities began a smart transition through widespread urban regeneration projects and the introduction of advanced technologies applied not only to the physical city but also to governance, policymaking, and communication, involving multiple sectors of city administrations. In the last decade, medium-sized cities have also started this transition process, although with lower emphasis than metropolitan cities. In most medium-sized Italian cities, this transition, in accordance with national and regional guidelines, has sometimes led to competencies reorganization within local governments. Within this framework, the paper examines the tools with which medium-sized Italian cities’ administrations address the smart transformation in their territories, comparing a sample of 10 cities in Emilia-Romagna and considering policymaking, governance structure, past and current projects, and communication transparency. The expected result is therefore a systematic review of experiences to reconstruct a complex picture of the political and administrative choices that have led to the implementation or setting in motion of smart transformation processes to draw some useful lessons

DECLINE OF PREVALENCE OF RESISTANCE ASSOCIATED SUBSTITUTIONS TO NS3 AND NS5A INHIBITORS AT DAA- FAILURE IN HEPATITIS C VIRUS IN ITALY OVER THE YEARS 2015 TO 2018

Background: A minority of patients fails to eliminate HCV and resistance-associated substitutions (RASs) are commonly detected at failure of interferon-free DAA regimens . Methods: Within the Italian network VIRONET-C, the prevalence of NS3/NS5A/NS5B RASs was retrospectively evaluated in patients who failed an EASL recommended DAA-regimen in 2015-2018 . The geno2pheno system and Sorbo MC et al. Drug Resistance Updates 2018 were used to infer HCV- genotype/subtype and predict drug resistance . The changes in prevalence of RASs over time were evaluated by chi-square test for trend, predictors of RASs at failure were analysed by logistic regression . Results: We included 386 HCV infected patients: 75% males, median age was 56 years (IQR 52-61), metavir fibrosis stage F4 in 76%; 106 (28%) were treatment- experienced: 91 (86%) with IFN-based treatments, 26 (25%) with DAAs. Patients with HIV and HBV coinfection were 10% (33/317) and 8% (6/72), respectively. HCV genotype was 1b in 122 pts (32%), 3 in 109 (28%), 1a in 97 (25%), 4 in 37 (10%), 2 in 21 (5%). DAA regimens were: LDV/SOF in 115 (30%), DCV/SOF in 103 (27%), 3D in 83 (21%), EBR/GRZ in 32 (8%), VEL/SOF in 29 (7%), GLE/PIB in 18 (5%) and 2D in 6 (2%); ribavirin was administered in 123 (32%) . The NS5A fasta-sequence was available for all patients, NS5B for 361 (94%), NS3 for 365 (95%) . According to the DAA failed the prevalence of any RASs was 90%, namely 80/135 (59%) in NS3, 313/359 (87%) in NS5A, 114/286 (40%) in NS5B . The prevalence of any RASs significantly declined from 2015 to 2018 (93% vs 70%, p=0.004): NS5A RASs from 90% to 72% (p=0 .29), NS3 RASs from 74% to 18% (p<0 .001), while NS5B RASs remained stable . Independent predictors of any RASs included advanced fibrosis (AOR 6.1, CI 95% 1.8-20.3, p=0 .004) and genotype (G2 vs G1a AOR 0 .03, CI 95% 0 .002- 0 .31, p=0 .004; G3 vs G1a AOR 0 .08, CI 95% 0 .01-0 .62, p=0 .02; G4 vs G1a AOR 0 .05, CI 95% 0 .006-0 .46, p=0 .008), after adjusting for age, previous HCV treatment and year of genotype . Notably, full activity was predicted for GLE/PIB in 75% of cases and for at least two components of VEL/SOF/VOX in 53% of cases, no case with full-resistance to either regimen was found . Conclusion: Despite decreasing prevalence over the years, RASs remain common at virological failure of DAA treatment, particularly in patients with the highest grade of liver fibrosis. The identification of RASs after failure could play a crucial role in optimizing retreatment strategies

Urban regeneration to enhance sustainable mobility

Urban regeneration processes represent an opportunity to pursue a sustainable city model. From a sustainable city perspective, the contribution to the redesign of public space and mobility infrastructures and to the improvement of pedestrian and cycle accessibility to local public services is undoubtedly significant. Within this framework, the Italian Region of Emilia-Romagna, promoted an Urban regeneration Call in 2018 to which cities submitted project proposals concerning the redevelopment of both architectural emergencies and public open spaces, paying particular attention to sustainable mobility issues. About 100 proposals have been submitted and several municipalities received funding. This paper analyses in particular the proposals submitted by the provincial capital cities, through a comparative approach, focusing on mobility, accessibility improvements and open space redevelopment. The aim is to highlight similarities and differences in order to identify some common guiding principles for enhancing sustainable urban mobility

Sustainable Mobility and Accessibility to Essential Services. An Assessment of the San Benedetto Neighbourhood in Cagliari (Italy)

In line with the leading European directives, i.e. the Sustainable Goals of the 2030 Agenda, concerning urban development and emissions reduction, the authors find in the 15-min city a model that prioritises active mobility as the main way to reach services within a neighbourhood. The paper is based on the concept of the Smart City (SC), which is defined as a city capable of serving and integrating the demands of individual citizens while concentrating on sustainability and hence on environmentally friendly lifestyles. In this context, the paper highlights pedestrian and bicycle accessibility in relation to essential services, by considering the San Benedetto neighbourhood in the city of Cagliari as a case study. The pedestrian accessibility to essential services is measured in a range of influences based on home-service travel times between 5 and 15 min, using a GIS tool. The contribution aims at identifying action plans for implementing local mobility strategies

Ribavirin transporter [Ent1] polymorphism is a pretreatment predictor of virologic response. the specific role of donor liver transporter

The genetic polymorphism of Equilibrative Nucleoside Transporter 1 [ENT1] is involved in ribavirin cellular uptake and it could positively enhance antiviral treatment response. The liver transplant setting offers the unique opportunity to selectively observe the effect(s) of the donor liver ENT1 gene on HCV treatment outcome. We aimed at studying donor polymorphism of ENT1 and HCV therapy outcome in transplanted patients. The role of ribavirin plasma concentration was evaluated. 39 patients after HCV recurrence were included. Genotyping of donor ENT1 and of IL-28B was performed in donor liver samples by RNA PCR. Allelic frequencies of liver ENT1 were: AA 43.6%; AG 28.2%; GG 28.2%. GG genotype was associated with rapid [RR=8; 95% CI 1.6-38; p=0.01] and sustained virological response [RR=9.5; 95% CI 1.6-53; p=0.01]. In multivariate analysis, GG genotype and a ribavirin plasma concentration >2.0 ng/mL at week 12 were independently associated with sustained virological response. In conclusion, the genetic polymorphism of ENT influences treatment response and a pre-treatment determination of its activity could help to predict treatment response in HCV patients

Impact of new DAA therapy on real clinical practice: a multicenter region-wide cohort study

Abstract Background Management of chronic hepatitis C (CHC) has significantly accelerated in the last few years. Currently, second generation direct acting antivirals (DAAs) promise clearance of infection in most of patients. Here we present the results of the first analysis carried out on data of Lazio clinical network for DAAs. Methods The study was designed as a multicenter cohort: a) to assess the evolution of treatment during the first 24 months of the activity of the Clinical Network; b) to report overall efficacy of treatments; c) to analyze potential factors associated with lack of virological response at 12 weeks after therapy (SVR12); d) to evaluate the variation of ALT at baseline and 12 weeks after therapy in those who achieved SVR12 in comparison to those who did not. Analyses of efficacy were carried out with multilevel mixed effect logistic regression model. ALT temporal variation was assessed by mixed effect model mixed models with random intercept at patient’s level and random slope at the level of the time; i.e. either before or after therapy. Results Between 30 December 2014 and 31 December 2016 5279 patients started a DAA treatment; of those, 5127 (in 14 clinical centers) had completed the 12-week follow-up. Overall proportion of SVR12 was 93.41% (N = 4780) with no heterogeneity between the 14 clinical centers. Interruption as the consequence of severe side effect was very low (only 23 patients). Unadjusted analysis indicates that proportion of SVR12 significantly changes according to patient’s baseline characteristics, however after adjusting for potential confounders only adherence to current guidelines, stage of liver diseases, gender, transplant and HIV status were independently associated with the response to therapy. Analysis of ALT temporal variation showed that ALT level normalized in most, but not, all patients who achieved SVR12. Conclusion Our study confirmed the extraordinary efficacy of DAAs outside clinical trials. The advantage of DAAs was particularly significant for those patients who were previously considered as difficult-to-treat and did not have treatment options before DAAs era. Intervention based on network of select centers and prioritization of patients according to diseases severity was successful. Further studies are needed to establish whether clearance of HCV after DAAs therapy can arrest or even revert liver fibrosis in non-cirrhotic patients and/or improve life quality and expectancy in those who achieve SVR12 with cirrhosis

Hepatitis C virus RNA levels at week-2 of telaprevir/boceprevir administration are predictive of virological outcome

Background: Triple therapy with telaprevir/boceprevir + pegylated-interferon + ribavirin can achieve excellent antiviral efficacy, but it can be burdened with resistance development at failure. Aims: To evaluate kinetics of hepatitis C virus (HCV) RNA decay and early resistance development, in order to promptly identify patients at highest risk of failure to first generation protease inhibitors. Methods: HCV-RNA was prospectively quantified in 158 patients receiving pegylatedinterferon + ribavirin + telaprevir (N = 114) or + boceprevir (N = 44), at early time-points and during per protocol follow-up. Drug resistance was contextually evaluated by population sequencing. Results: HCV-RNA at week-2 was significantly higher in patients experiencing virological failure to triple-therapy than in patients with sustained viral response (2.3 [1.9–2.8] versus 1.2 [0.3–1.7] log IU/mL, p < 0.001). A 100 IU/mL cut-off value for week-2 HCV-RNA had the highest sensitivity (86%) in predicting virological success. Indeed, 23/23 (100%) patients with undetectable HCV-RNA reached success, versus 26/34 (76.5%) patients with HCV-RNA < 100 IU/mL, and only 11/31 (35.5%) with HCV-RNA > 100 IU/mL (p < 0.001). Furthermore, differently from failing patients, none of the patient with undetectable HCV-RNA at week-2 had baseline/early resistance. , Giuliano Rizzardinil, Mario Angelicob