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Purpose: Higher education institutions draw up codes of ethics, but in several countries there are no standards to follow. Most universities have autonomy and can freely draw up their codes of ethics in terms of structure and content. The purpose of this paper is to understand the main ethics issues that universities identify in their codes of ethics and what activities they implement to respond to these issues toward appropriate educational management of their institutions in ethical terms. Design/methodology/approach: This study was performed through content analysis of codes of ethics of Italian public universities (64 codes), and may be considered a single in-depth case study. The main ethics issues and related activities were inductively codified in relation to the research purpose. The four constitutive aspects of business ethics (individual, managerial, organizational and societal ethics) proposed by Melé were chosen as the framework to investigate the main ethical needs and related activities implemented by universities to respond to these ethical issues. Findings: This research has identified nine main ethical issues and related activities that contribute to guarantee the ethical compliance of universities under the four interrelated aspects different individual behaviors, managerial initiatives, organization strategies and responsibilities toward society. The analysis shows some relevant differences among Italian universities that have important implications in the ethical vision of academic communities and of managerial role in universities. Practical implications: The research can help managers of higher education institutions to identify the main ethical issues to draw up codes of ethics and to formulate consistent development strategies that are able to improve the conditions of collaboration, work and productive participation in activities for all members of academic communities. Originality/value: To the best of the authors' knowledge, this is one of the first studies that connect codes of ethics and higher education. This research brings to light the main ethical issues and related activities that universities can consider to orient their strategic choices toward the public interest as well as educational management improvement.

Purpose: This paper aims to examine the content dimensions and methods of accelerating the entrepreneurial learning (EL) triggered by participating in learning events, such as factory tours. It particularly focuses on the Italian case of Open Factory -- an open-doors event of industrial manufacturing culture. Design/methodology/approach: This study adopted a qualitative approach using the "Gioia" methodology. Data were mainly collected through semi-structured interviews with firms participating in and organising Open Factory. Findings: The dimensions of EL are learning from critical reflection, experience and external sources, while the enablers of EL (factors that accelerate learning) are varied and connected to organisational learning in the form of individual-, team- and institutional-level learning. Based on these results, this paper proposes a model for developing EL triggered by participating in learning events. Practical implications: This research suggests developing appropriate organisational conditions inside firms, especially by entrepreneurs. These conditions are connected to sharing organisational values to foster learning, such as trust, commitment, involvement, awareness, sharing of experiences, exchange, autonomy and freedom. In addition, this study suggests ways that the EL model proposed in this research can be adapted to other learning events. Originality/value: This is the first study to connect factory tours to learning events and EL. It highlights the ways that participating in the Open Factory event created the chance to develop learning across organisational levels inside firms.

Family labor migration from South Asia to Europe is often framed as proceeding in a predictable pattern of "male first-time migrant, ethnic marriage and spouse reunion." Migration to Northern Italy is no exception. Primary data from recent ethnographic fieldwork reveal a slow rise in mixed South Asian–Italian couples, which might bring into question the quandaries they face in raising children. This article considers the daily struggles in conjugal and parental relations in mixed-culture households formed by spouses, one of whom is from a South Asian background, and the other is an Italian "native." Applying intersectional analysis to the life stories and aspirations of such cross-cultural new generations allows for revisiting the commonplace view of South Asia–Europe intimate links. [ABSTRACT FROM AUTHOR]

Objectives: The management of HIV disease is complicated by the incidence of a new spectrum of comorbid noncommunicable diseases (NCDs). It is important to document changes in the prevalence of NCDs over time. The aim of the study was to describe the impact of ageing on HIV markers and on the prevalence of NCDs in people living with HIV (PLWHIV) in the Italian Cohort of Individuals, Naïve for Antiretrovirals (ICONA) seen for care in 2004–2014. Methods: Analyses were conducted separately for a closed cohort (same people seen at both times) and an open cohort (all people under follow‐up). We used the χ2 test for categorical factors and the Wilcoxon test for quantitative factors to compare profiles over time. Results: The closed cohort included 1517 participants and the open cohort 3668 under follow‐up in 2004 and 6679 in 2014. The median age of the open cohort was 41 [interquartile range (IQR) 37–46] years in 2004 and 44 (IQR 36–52) years in 2014. Analysis of the closed cohort showed an increase in the prevalence of some NCDs [the prevalence of dyslipidaemia increased from 75% in 2004 to 91% in 2014, that of hypertension from 67 to 84%, and that of cardiovascular disease (CVD) from 18 to 32%] and a decrease in renal function (5% with eGFR < 60 mL/min per 1.73 m2 in 2004 versus 30% in 2014); the percentage of people in the high‐risk group for the Framingham CHD score more than tripled (from 13 to 45%). Results in the open cohort were similar. Conclusions: The burden of NCDs in our PLWHIV population markedly worsened over a 10‐year time‐span, which is likely to be a result of the effects of both ageing and HIV infection as well as their interaction. Special attention must be given to the management and prevention of NCDs. [ABSTRACT FROM AUTHOR]

Copyright of ALTER: European Journal of Disability Research, Journal Europeen de Erche sur le Handicap is the property of European Society for Disability Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: The first comprehensive geochemical data-set of the fluids circulating over a 14,000 km2-wide seismic-prone area of the Southern Apennines, Calabria Region (Italy), is presented here. The geochemical investigations were carried out with the twofold aim of constraining the origin and interactions of the circulating fluids and to investigate possible relationships with local faults. Sixty samples of both thermal and cold waters were collected, from which the dissolved gases were extracted. The geochemical features of the water samples display different types and degrees of water–rock interactions, irrespective of the outlet temperature. The calculated equilibrium temperatures of the thermal waters (60–160°C) and the low heat flow of the whole study area, are consistent with a heating process due to deep water circulation and rapid upflow through lithospheric structures. The composition of the dissolved gases reveals that crustal-originating gases (N2 and CO2-dominated) feed all the groundwaters. The 3He/4He ratios of the dissolved He, in the range of 0.03–0.22Rac for the thermal waters and 0.05–0.63Rac for the cold waters (Rac =He isotope ratio corrected for atmospheric contamination), are mainly the result of a two-component (radiogenic and atmospheric) mixing, although indications of mantle-derived He are found in some cold waters. As the study area had been hit by 18 of the most destructive earthquakes (magnitude ranging from 5.9 to 7.2) occurring over a 280-a time span (1626–1908) in the Southern Apennines, the reported results on the circulating fluids may represent the reference for a better inside knowledge of the fault-fluid relationships and for the development of long-term geochemical monitoring strategies for the area. [Copyright &y& Elsevier]

The article explores the prevalence and control of low pathogenicity avian influenza (LPAI) in 2007 and 2008 in Italy. From May to October 2007, 10 rural and hobby poultry farms were reported to be infected by LPAI virus H7N3 subtype. The same subtype was found in sex meat turkey farms between August and October 2007. In July 2007, hemagglutinin and neuraminidase genes were discovered to have a high level of homology with H5N2 subtype of LPAI virus among mallards. According to the authors, the implementation of avian influenza control, along with an emergency vaccination effort, eradicate LPAI infection.

Major ion content of 37 wet-only rainwater samples collected on the southern flank of Mount Etna volcano was investigated. Measured pH values range from 3.80 to 7.22 and display a positive correlation with Ca2 + and an inverse correlation with NO3-, suggesting that anthropogenic NOx are the most effective acidifying agents while Ca, likely as solid CaCO3, is the prevailing proton acceptor. Na/Cl ratios indicate a dominant marine origin for both species, while K, mg and Ca contents point to additional sources (soil dust, fertilisers etc.). Nitrate and sulphate concentrations display a nearly constant ratio indicating a common anthropogenic origin, and only a few samples are characterised by sulphate excess. The analysis of time series reveals a good correlation between the excess sulphate in rainwater and SO2 fluxes from the summit craters plume. Non sea salt chloride contents show also a significant correlation with volcanic activity indicating a magmatic sulphur and chloride contribution to rainwater. Meteoric flux estimations point to a prevailing magmatic origin for sulphur in the collected rainwaters while sea spray is the main source of chlorine. [ABSTRACT FROM AUTHOR]

As glyphosate-based herbicides, sold under the commercial name Roundup®, represent the most used herbicides in the world, contamination of the freshwater environment by glyphosate has become a widespread issue. In Italy, glyphosate was detected in half of the surface waters monitoring sites and its concentrations were higher than environmental quality standards in 24.5% of them. It can last from days to months in water, leading to exposure for aquatic organisms and specifically to amphibians' larvae that develop in shallow water bodies with proven effects to development and behaviour. In this study, we tested the effects of a 96 h exposure during embryonic development of marsh frog's tadpoles to three ecologically relevant Roundup® Power 2.0 concentrations. As expected, given the low concentrations tested, no mortality was observed. Morphological measurements highlighted a reduction in the total length in tadpoles exposed to 7.6 mg a.e./L, while an increase was observed at lower concentrations of 0.7 and 3.1 mg a.e./L compared to control group. Tadpoles raised in 7.6 mg a.e./L also showed a smaller tail membrane than those raised in the control solution. Regarding behaviour, we tested tadpoles in two different sessions (Gosner stages 25 and 28/29) for lateralization, antipredator response and basal activity. Lower intensity of lateralization was detected in tadpoles raised at the highest Roundup® concentration in the first session of observation, while no significant difference among treatments was observed in the second one. In both sessions, effects of Roundup® Power 2.0 embryonic exposure on antipredator response, measured as the proportional change in activity after the injection of tadpole-fed predator (Anax imperator) cue, were not detected. Tadpoles exposed during embryonic development to Roundup® exhibited lower basal activity than the control group, with the strongest reduction for the 7.6 mg a.e./L treatment. Our results reinforce the concern of Roundup® contamination impact on amphibians. Image 1 • Marsh frog's embryos were exposed to three Roundup® Power 2.0 concentrations. • Tadpole's morphology was negatively affected by the highest RU-PW treatment. • Hatched tadpoles exposed to the highest RU-PW showed a low lateralization index. • Tadpoles basal activity was strongly reduced by RU-PW exposures. [ABSTRACT FROM AUTHOR]

The article presents a study focusing on metabolic syndrome (MS) as a primary risk factor for diabetes and cardiovascular disease among HIV-infected patients. The measurement of waist circumference (WC) was recommended by the European Clinical Society as it is an essential component of MS, based on the correlation between central obesity and insulin resistance. Researchers proposed that the measurement of MS should be properly assessed to determine the prevalence and characteristics of MS.

Background: The coexistence of HIV infection and latent tuberculosis infection (LTBI) presents a significant public health concern due to the increased risk of tuberculosis (TB) reactivation and progression to active disease. The multicenter observational cohort study, TUBHIVIT, conducted in Italy from 2017 to 2023, aimed to assess the prevalence of LTBI among people living with HIV (PLHIV) and their outcomes following LTBI screening and therapy initiation., Methods: We performed a prospective study in five referral centers for HIV care in Italy. PLHIV who consented Tto participate underwent QuantiFERON-TB Gold Plus and clinical, microbiological, and radiological assessments to exclude subclinical tuberculosis, as opportune. PLHIV diagnosed with LTBI who started chemoprophylaxis were followed until the end of therapy., Results: A total of 1105 PLHIV were screened for LTBI using the QuantiFERON-TB Gold Plus test, revealing a prevalence of 3.4% of positive results (38/1105). Non-Italy-born individuals exhibited a significantly higher likelihood of testing positive. Thirty-one were diagnosed with LTBI, 1 showed active subclinical TB, and 6 were lost to follow-up before discriminating between latent and active TB. Among the PLHIV diagnosed with LTBI, 83.9% (26/31) started chemoprophylaxis. Most individuals received 6-9 months of isoniazid-based therapy. Of the 26 PLHIV commencing chemoprophylaxis, 18 (69.2%) completed the therapy, while 3 discontinued it and 5 were still on treatment at the time of the analysis. Adverse events were observed in two cases, while in one case the patient refused to continue the treatment.

Background: Mpox virus (MPXV) has recently spread outside of sub-Saharan Africa. This large multicentre study was conducted in Lombardy, the most densely populated Italian region accounting for more than 40% of Italian cases. The present study aims to: i) evaluate the presence and the shedding duration of MPXV DNA in different body compartments correlating the MPXV viability with the time to onset of symptoms; ii) provide evidence of MPXV persistence in different body compartment as a source of infection and iii) characterize the MPXV evolution by whole genome sequencing (WGS) during the outbreak occurred in Italy., Material and Methods: The study included 353 patients with a laboratory-confirmed diagnosis of MPXV infection screened in several clinical specimens in the period May 24th - September 1st, 2022. Viral isolation was attempted from different biological matrices and complete genome sequencing was performed for 61 MPXV strains., Results: MPXV DNA detection was more frequent in the skin (94.4%) with the longest median time of viral clearance (16 days). The actively-replicating virus in cell culture was obtained for 123/377 (32.6%) samples with a significant higher viral quantity on isolation positive samples (20 vs 31, p < 0.001). The phylogenetic analysis highlighted the high genetic identity of the MPXV strains collected, both globally and within the Lombardy region., Conclusion: Skin lesion is gold standard material and the high viral load and the actively-replicating virus observed in genital sites confirms that sexual contact plays a key role in the viral transmission., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Injectable cabotegravir and rilpivirine long-acting therapy is a revolutionary new antiretroviral treatment (ART) option for HIV infection in virologically suppressed adults on a stable ART. The aim of this study from SCOLTA multicenter observational prospective database is to describe the first people living with HIV (PWH) who started this regimen in Italy, assessing adherence to eligibility criteria, describing clinical-epidemiological characteristics compared to registration trials-population and describe early treatment-discontinuations., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Understanding the cause of sex disparities in COVID-19 outcomes is a major challenge. We investigate sex hormone levels and their association with outcomes in COVID-19 patients, stratified by sex and age. This observational, retrospective, cohort study included 138 patients aged 18 years or older with COVID-19, hospitalized in Italy between February 1 and May 30, 2020. The association between sex hormones (testosterone, estradiol, progesterone, dehydroepiandrosterone) and outcomes (ARDS, severe COVID-19, in-hospital mortality) was explored in 120 patients aged 50 years and over. STROBE checklist was followed. The median age was 73.5 years [IQR 61, 82]; 55.8% were male. In older males, testosterone was lower if ARDS and severe COVID-19 were reported than if not (3.6 vs. 5.3 nmol/L, p =0.0378 and 3.7 vs. 8.5 nmol/L, p =0.0011, respectively). Deceased males had lower testosterone (2.4 vs. 4.8 nmol/L, p =0.0536) and higher estradiol than survivors (40 vs. 24 pg/mL, p = 0.0006). Testosterone was negatively associated with ARDS (OR 0.849 [95% CI 0.734, 0.982]), severe COVID-19 (OR 0.691 [95% CI 0.546, 0.874]), and in-hospital mortality (OR 0.742 [95% CI 0.566, 0.972]), regardless of potential confounders, though confirmed only in the regression model on males. Higher estradiol was associated with a higher probability of death (OR 1.051 [95% CI 1.018, 1.084]), confirmed in both sex models. In males, higher testosterone seems to be protective against any considered outcome. Higher estradiol was associated with a higher probability of death in both sexes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Beltrame, Salguero, Rossi, Conesa, Moro, Bettini, Rizzi, D’Angió, Deiana, Piubelli, Rebora, Duranti, Bonfanti, Capua, Tarazona and Valsecchi.)

Importance: Convalescent plasma (CP) has been generally unsuccessful in preventing worsening of respiratory failure or death in hospitalized patients with COVID-19 pneumonia., Objective: To evaluate the efficacy of CP plus standard therapy (ST) vs ST alone in preventing worsening respiratory failure or death in patients with COVID-19 pneumonia., Design, Setting, and Participants: This prospective, open-label, randomized clinical trial enrolled (1:1 ratio) hospitalized patients with COVID-19 pneumonia to receive CP plus ST or ST alone between July 15 and December 8, 2020, at 27 clinical sites in Italy. Hospitalized adults with COVID-19 pneumonia and a partial pressure of oxygen-to-fraction of inspired oxygen (Pao2/Fio2) ratio between 350 and 200 mm Hg were eligible., Interventions: Patients in the experimental group received intravenous high-titer CP (≥1:160, by microneutralization test) plus ST. The volume of infused CP was 200 mL given from 1 to a maximum of 3 infusions. Patients in the control group received ST, represented by remdesivir, glucocorticoids, and low-molecular weight heparin, according to the Agenzia Italiana del Farmaco recommendations., Main Outcomes and Measures: The primary outcome was a composite of worsening respiratory failure (Pao2/Fio2 ratio <150 mm Hg) or death within 30 days from randomization., Results: Of the 487 randomized patients (241 to CP plus ST; 246 to ST alone), 312 (64.1%) were men; the median (IQR) age was 64 (54.0-74.0) years. The modified intention-to-treat population included 473 patients. The primary end point occurred in 59 of 231 patients (25.5%) treated with CP and ST and in 67 of 239 patients (28.0%) who received ST (odds ratio, 0.88; 95% CI, 0.59-1.33; P = .54). Adverse events occurred more frequently in the CP group (12 of 241 [5.0%]) compared with the control group (4 of 246 [1.6%]; P = .04)., Conclusions and Relevance: In patients with moderate to severe COVID-19 pneumonia, high-titer anti-SARS-CoV-2 CP did not reduce the progression to severe respiratory failure or death within 30 days., Trial Registration: ClinicalTrials.gov Identifier: NCT04716556.

Type-I interferons (IFNs) mediate antiviral activity and have emerged as important immune mediators during coronavirus disease 19 (COVID-19). Several lines of evidence suggest that impaired type-I IFN signaling may predispose to severe COVID-19. However, the pathophysiologic mechanisms that contribute to illness severity remain unclear. In this study, our goal was to gain insight into how type-I IFNs influence outcomes in patients with COVID-19. To achieve this goal, we compared clinical outcomes between 26 patients with neutralizing type-I IFN autoantibodies (AAbs) and 192 patients without AAbs who were hospitalized for COVID-19 at three Italian hospitals. The presence of circulating AAbs to type-I IFNs was associated with an increased risk of admission to the intensive care unit and a delayed time to viral clearance. However, survival was not adversely affected by the presence of type-I IFN AAbs. Our findings provide further support for the role of type-I IFN AAbs in impairing host antiviral defense and promoting the development of critical COVID-19 pneumonia in severe acute respiratory syndrome coronavirus 2-infected individuals., (© 2021 Australian and New Zealand Society for Immunology, Inc. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Introduction: A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality., Aim: We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients., Methods: In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores., Results: Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio = 0.60; 95% confidence interval: 0.49-0.74; E-value = 2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation., Conclusion: In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations., Competing Interests: None declared., (Thieme. All rights reserved.)

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February-May 2020). Patients' characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction ( p < 0.001). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Augusto Di Castelnuovo et al.)

Objectives: The aims of this study are to report the prevalence of delirium on admission to the unit in patients hospitalized with SARS-CoV-2 infection, to identify the factors associated with delirium, and to evaluate the association between delirium and in-hospital mortality., Design: Multicenter observational cohort study., Settings: Acute medical units in four Italian hospitals., Participants: A total of 516 patients (median age 78 years) admitted to the participating centers with SARS-CoV-2 infection from February 22 to May 17, 2020., Measurements: Comprehensive medical assessment with detailed history, physical examinations, functional status, laboratory and imaging procedures. On admission, delirium was determined by the Diagnostic and Statistical Manual of Mental Disorders (5th edition) criteria, 4AT, m-Richmond Agitation Sedation Scale, or clinical impression depending on the site. The primary outcomes were delirium rates and in-hospital mortality., Results: Overall, 73 (14.1%, 95% confidence interval (CI) = 11.0-17.3%) patients presented delirium on admission. Factors significantly associated with delirium were dementia (odds ratio, OR = 4.66, 95% CI = 2.03-10.69), the number of chronic diseases (OR = 1.20, 95% CI = 1.03; 1.40), and chest X-ray or CT opacity (OR = 3.29, 95% CI = 1.12-9.64 and 3.35, 95% CI = 1.07-10.47, for multiple or bilateral opacities and single opacity vs no opacity, respectively). There were 148 (33.4%) in-hospital deaths in the no-delirium group and 43 (58.9%) in the delirium group (P-value assessed using the Gray test <.001). As assessed by a multivariable Cox model, patients with delirium on admission showed an almost twofold increased hazard ratio for in-hospital mortality with respect to patients without delirium (hazard ratio = 1.88, 95% CI = 1.25-2.83)., Conclusion: Delirium is prevalent and associated with in-hospital mortality among older patients hospitalized with SARS-CoV-2 infection., (© 2020 The American Geriatrics Society.)

Background: During the Coronavirus disease 2019 (COVID-19) pandemic, advanced health systems have come under pressure by the unprecedented high volume of patients needing urgent care. The impact on mortality of this "patients' burden" has not been determined., Methods and Findings: Through retrieval of administrative data from a large referral hospital of Northern Italy, we determined Aalen-Johansen cumulative incidence curves to describe the in-hospital mortality, stratified by fixed covariates. Age- and sex-adjusted Cox models were used to quantify the effect on mortality of variables deemed to reflect the stress on the hospital system, namely the time-dependent number of daily admissions and of total hospitalized patients, and the calendar period. Of the 1225 subjects hospitalized for COVID-19 between February 20 and May 13, 283 died (30-day mortality rate 24%) after a median follow-up of 14 days (interquartile range 5-19). Hospitalizations increased progressively until a peak of 465 subjects on March 26, then declined. The risk of death, adjusted for age and sex, increased for a higher number of daily admissions (adjusted hazard ratio [AHR] per an incremental daily admission of 10 patients: 1.13, 95% Confidence Intervals [CI] 1.05-1.22, p = 0.0014), and for a higher total number of hospitalized patients (AHR per an increase of 50 patients in the total number of hospitalized subjects: 1.11, 95%CI 1.04-1.17, p = 0.0004), while was lower for the calendar period after the peak (AHR 0.56, 95%CI 0.43-0.72, p<0.0001). A validation was conducted on a dataset from another hospital where 500 subjects were hospitalized for COVID-19 in the same period. Figures were consistent in terms of impact of daily admissions, daily census, and calendar period on in-hospital mortality., Conclusions: The pressure of a high volume of severely ill patients suffering from COVID-19 has a measurable independent impact on in-hospital mortality., Competing Interests: The authors have declared that no competing interests exist.

Background & Aims: Coronavirus disease 2019 (COVID-19) poses a major health threat to healthy individuals and those with comorbidities, but its impact on patients with cirrhosis is currently unknown. Herein, we aimed to evaluate the impact of COVID-19 on the clinical outcome of patients with cirrhosis., Methods: In this multicentre retrospective study, patients with cirrhosis and a confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection were enrolled between 1 st and 31 th March 2020. Clinical and biochemical data at diagnosis of COVID-19 and at the last outpatient visit were obtained through review of medical records., Results: Fifty patients with cirrhosis and confirmed SARS-CoV-2 infection were enrolled (age 67 years, 70% men, 38% virus-related, 52% previously compensated cirrhosis). At diagnosis, 64% of patients presented fever, 42% shortness of breath/polypnea, 22% encephalopathy, 96% needed hospitalization or a prolonged stay if already in hospital. Respiratory support was necessary in 71%, 52% received antivirals, 80% heparin. Serum albumin significantly decreased, while bilirubin, creatinine and prothrombin time significantly increased at COVID-19 diagnosis compared to last available data. The proportion of patients with a model for end-stage liver disease (MELD) score ≥15 increased from 13% to 26% (p = 0.037), acute-on-chronic liver failure and de novo acute liver injury occurred in 14 (28%) and 10 patients, respectively. Seventeen patients died after a median of 10 (4-13) days from COVID-19 diagnosis, with a 30-day-mortality rate of 34%. The severity of lung and liver (according to CLIF-C, CLIF-OF and MELD scores) diseases independently predicted mortality. In patients with cirrhosis, mortality was significantly higher in those with COVID-19 than in those hospitalized for bacterial infections., Conclusion: COVID-19 is associated with liver function deterioration and elevated mortality in patients with cirrhosis., Lay Summary: Coronavirus disease 2019 (COVID-19) poses a major health threat to healthy individuals and those with comorbidities. Herein, we assessed its impact on patients with cirrhosis. Infection with COVID-19 was associated with liver function deterioration and elevated mortality in patients with cirrhosis., Competing Interests: Conflict of interest Massimo Iavarone: Speaking/Teaching, consultant and advisory board for Bayer, Gilead Sciences, BMS, Janssen, Ipsen, MSD, BTG-Boston Scientific, AbbVie, Guerbet, EISAI; Roberta D'Ambrosio: teaching and speaking for AbbVie, Gilead, MSD; Advisory Board for AbbVie, MSD, Research Grant from Gilead; Alessandro Soria: Speaking/Teaching, consultant and advisory board for AbbVie, MSD, Gilead; Mauro Viganò: speaking and teaching for Fujirebio, Intercept, Gilead; Alessio Aghemo: Advisory Board/Speaker Bureau for: Gilead, AbbVie, Intercept, MSD, Mylan and Alfasigma, Research grants from Gilead and Abbvie; Stefano Fagiuoli: Advisory Board/Speaker Bureau for Gilead, AbbVie, Novartis, MSD, Bayer, Intercept, Kedrion; Pietro Invernizzi: Advisory Board/Speaker Bureau for Gilead, Intercept, Bruschettini, AbbVie, MSD; Pietro Lampertico: Advisory Board/Speaker Bureau for BMS, Roche, Gilead, GSK, AbbVie, MSD, Arrowhead, Alnylam, Janssen, Spring Bank, MYR, Eiger. The other authors declare no conflict of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients., Methods: A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival., Results: In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P = 0.52) and 22.4% (97.5% CI: 17.2-28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline., Conclusions: Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

Background: Tobacco use is a leading cause of preventable diseases and death for all individuals, even more so for people living with HIV (PLWH), due to their status of chronic inflammation. To date, in Italy no study was performed to compare smoking habits in PLWH and the general population. We aimed to investigate smoking habits in PLWH, as compared to the general population., Methods: Multi-center cross-sectional study. Smoking habits were compared between PLWH and the general population. PLWH were enrolled in the STOPSHIV Study. The comparison group from the general population was derived from a survey performed by the National Statistics Institute (ISTAT), with a stratified random sampling procedure matching 2:1 general population subjects with PLWH by age class, sex, and macro-area of residence., Results: The total sample consisted of 1087 PLWH (age 47.9 ± 10.8 years, male 73.5%) and 2218 comparable subjects from the general population. Prevalence of current smokers was 51.6% vs 25.9% (p < 0.001); quitting smoking rate was 27.1% vs. 50.1% (p < 0.001) and the mean number of cigarettes smoked per day was 15.8 vs. 11.9 (p < 0.001), respectively for PLWH and the general population. Smoking and heavy smoking rates amongst PLWH were significantly higher even in subjects who reported diabetes, hypertension and extreme obesity (p < 0.001). Logistic regressions showed that PLWH were more likely current smokers (adjusted Odds Ratio, aOR = 3.11; 95% Confidence Interval (CI) =2.62-3.71; p < 0.001) and heavy smokers (> 20 cigarettes per day) (aOR = 4.84; 95% CI = 3.74-6.27; p < 0.001). PLWH were less likely to have quitted smoking (aOR = 0.36; 95% CI = 0.29-0.46; p < 0.001)., Conclusion: HIV-infected patients showed a higher rate of current smokers, a larger number of cigarettes smoked and a lower quitting rate than the general population. Our findings emphasize the need for smoking cessation strategies targeting HIV persons.

In a nationwide Italian sample of people living with HIV (PLWH), the prevalence of smoking, nicotine dependence, propensity to stop smoking, and cardiovascular profile were investigated. The nicotine dependence by Fagerström test and the propensity to stop according to the stages of change were evaluated. Associations between smoking habits and patients' characteristics were analyzed using an unconditional logistic regression model. Among 1,087 PLWH (age 47.9 ± 10.8 years, men 73.5%), the prevalence of current smokers was 51.6%. The median of Fagerström test was 4 (interquartile range 2-6); 60.1% of the smokers were in precontemplation, 17.6% in contemplation, 18.7% in preparation, and 3.6% in action. In a logistic multivariate model, current smoking was associated with male sex, being divorced/widowed, Caucasian ethnicity, dyslipidemia, atherosclerotic cardiovascular disease risk, psychiatric comorbidity, hepatitis C virus infection, and alcohol abuse. Low high-density lipoprotein cholesterol level was associated with high nicotine dependence. More than 50% of PLWH were current smokers, one-third of them showed a high or very high degree of dependence. Our findings draw attention to the need of smoking cessation strategies for PLWH.

Background & Aims: Sofosbuvir/velpatasivr/voxilaprevir (SOF/VEL/VOX) is approved for retreatment of patients with HCV and a previous failure on direct-acting antivirals (DAAs), however real-life data are limited. The aim of this study was to assess the effectiveness and safety of SOF/VEL/VOX in a real-life setting., Methods: All consecutive patients with HCV receiving SOF/VEL/VOX between May-October 2018 in 27 centers in Northern Italy were enrolled. Bridging fibrosis (F3) and cirrhosis (F4) were diagnosed by liver stiffness measurement: >10 and >13 kPa respectively. Sustained virological response (SVR) was defined as undetectable HCV-RNA 4 (SVR4) or 12 (SVR12) weeks after the end-of-treatment., Results: A total of 179 patients were included: median age 57 (18-88) years, 74% males, median HCV-RNA 1,081,817 (482-25,590,000) IU/ml. Fibrosis stage was F0-F2 in 32%, F3 in 21%, F4 in 44%. HCV genotype was 1 in 58% (1b 33%, 1a 24%, 1nc 1%), 2 in 10%, 3 in 23% and 4 in 9%; 82% of patients carried resistance-associated substitutions in the NS3, NS5A or NS5B regions. Patients received SOF/VEL/VOX for 12 weeks, ribavirin was added in 22% of treatment schedules. Undetectable HCV-RNA was achieved by 74% of patients at week 4 and by 99% at week 12. Overall, 162/179 (91%) patients by intention to treat analysis and 162/169 (96%) by per protocol analysis achieved SVR12, respectively; treatment failures included 6 relapsers and 1 virological non-responder. Cirrhosis (p = 0.005) and hepatocellular carcinoma (p = 0.02) were the only predictors of treatment failure. Most frequent adverse events included fatigue (6%), hyperbilirubinemia (6%) and anemia (4%)., Conclusions: SOF/VEL/VOX is an effective and safe retreatment for patients with HCV who have failed on a previous DAA course in a real-life setting., Lay Summary: This is the largest European real-life study evaluating effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) in a large cohort of consecutive patients with hepatitis C virus infection and a prior direct-acting antiviral failure, who were treated within the NAVIGATORE Lombardia and Veneto Networks, in Italy. This study demonstrated excellent effectiveness (98% and 96% sustained virological response rates at week 4 and 12, respectively) and an optimal safety profile of SOF/VEL/VOX. Cirrhosis and hepatocellular carcinoma onset were the only features associated with treatment failure., (Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

The aim of the study is to propose a multidimensional second-level diagnostic assessment to allow follow- up in the event physicians observe the presence of risk factors and/or active co-morbidities in HIV-infected patients. To develop our proposal, we chose the Delphi method that has been used for about 30 years in the healthcare field. The CISAI Group (Coordinamento Italiano per lo Studio dell'Allergia in Infezione da HIV) conducted this study. The first phase of the study provided identification of the questionnaire for second-level diagnostic assessment of HIV-infected patients. From March to July 2018 the questionnaire was submitted to 48 experts from 10 Italian HIV-dedicated sites. The questionnaire consisted of 102 items divided into 7 survey areas. The results can be summarized as follows: infectious disease diagnostics, 18 items reached agreement in 9 cases; osteoporosis diagnostics 12 items with 3 agreements; metabolic and cardiovascular diagnostics 13 items with 4 agreements; nephrology diagnostics 19 items with 8 agreements; hepatology diagnostics 12 items with 9 agreements; CNS diagnostics: 18 items with 7 agreements; psychological diagnostics and quality of life assessment (QoL) 10 items with no agreement. If these considerations are confirmed in required discussions and in-depth analyses, they will be able to produce an important indication in the drafting of national guidelines.

Background: Among people living with HIV (PLWH), the prevalence of non-HIV related co-morbidities is increasing. Aim of the present study is to describe co-morbidity and multi-morbidity, their clustering mode and the potential disease-disease interactions in a cohort of Italian HIV patients., Methods: Cross-sectional analysis conducted by the Coordinamento Italiano per lo Studio di Allergia e Infezioni da HIV (CISAI) on adult subjects attending HIV-outpatient facilities. Non-HIV co-morbidities included: cardiovascular disease, diabetes mellitus, hypertension, oncologic diseases, osteoporosis, probable case of chronic obstructive pulmonary disease (COPD), hepatitis C virus (HCV) infection, psychiatric illness, kidney disease. Multi-morbidity was defined as the presence of two or more co-morbidities., Results: One thousand and eighty-seven patients were enrolled in the study (mean age 47.9 ± 10.8). One hundred-ninety patients (17.5%) had no co-morbidity, whereas 285 (26.2%) had one condition and 612 (56.3%) were multi-morbid. The most recurrent associations were: 1) dyslipidemia + hypertension (237, 21.8%); 2) dyslipidemia + COPD (188, 17.3%); 3) COPD + HCV-Ab+ (141, 12.9%). Multi-morbidity was associated with older age, higher body mass index, current and former smoking, CDC stage C and longer ART duration., Conclusions: More than 50% of PLHW were multi-morbid and about 30% had three or more concurrent comorbidities. The identification of common patterns of comorbidities address the combined risks of multiple drug and disease-disease interactions.

Background and Aims: The efficacy and safety of glecaprevir/pibrentasvir (G/P) for patients infected with hepatitis C virus (HCV) have only been investigated in clinical trials, with no real-world data currently available. The aim of our study was to investigate the effectiveness and safety of G/P in a real-world setting., Methods: All patients with HCV consecutively starting G/P between October 2017 and January 2018 within the NAVIGATORE-Lombardia Network were analyzed. G/P was administered according to drug label (8, 12 or 16 weeks). Fibrosis was staged either histologically or by liver stiffness measurement. Sustained virological response (SVR) was defined as undetectable HCV-RNA 12 weeks after the end of treatment., Results: A total of 723 patients (50% males) were treated with G/P, 89% for 8 weeks. The median age of our cohort was 58 years, with a median body mass index of 23.9 kg/m 2 , and median liver stiffness measurement of 6.1 kPa; 84% were F0-2 and 16% were interferon-experienced. Median HCV-RNA was 1,102,600 IU/ml, and 49% of patients had HCV genotype 1 (32% 1b), 28% genotype 2, 10% genotype 3 and 13% genotype 4. The median estimated glomerular filtration rate was 90.2 ml/min, platelet count 209x10 3 /mm 3 and albumin 4.3 g/dl. The SVR rates were 94% in intention-to-treat and 99.3% in per protocol analysis (8-week vs. 12 or 16-week: 99.2% vs. 100%). Five patients failed therapy because of post-treatment relapse; a post-treatment NS5A resistance-associated substitution was detected in 1 case. SVR rates were lower in males (p = 0.002) and in HCV genotype-3 (p = 0.046) patients treated for 8 weeks, but independent of treatment duration, fibrosis stage, baseline HCV-RNA, HIV co-infection, chronic kidney disease stage and viral kinetics. Mild adverse events were reported in 8.3% of the patients, and 0.7% of them prematurely withdrew treatment. Three patients died of drug-unrelated causes., Conclusions: In a large real-world cohort of Italian patients, we confirmed the excellent effectiveness and safety of G/P administered for 8, 12 or 16 weeks., Lay Summary: A large number of patients with hepatitis C virus have been treated with glecaprevir/pibrentasvir (G/P) within the NAVIGATORE-Lombardia Network, in Italy. This is the first real-world study evaluating effectiveness and safety of G/P in patients with hepatitis C virus treated according to international recommendations. This study demonstrated excellent effectiveness (with sustained virological response rates of 99.3%) and safety profiles., (Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Social determinants are known to be a driving force of health inequalities, even in high income countries. Aim of our study was to determine if these factors can limit antiretroviral therapy (ART) access, outcome and retention in care of people living with HIV (PLHIV) in Italy., Methods: All ART naïve HIV+ patients (pts) of Italian nationality enrolled in the ICONA Cohort from 2002 to 2016 were included. The association of socio-demographic characteristics (age, sex, risk factor for HIV infection, educational level, occupational status and residency area) with time to: ART initiation (from the first positive anti-HIV test), ART regimen discontinuation, and first HIV-RNA < 50 cp/mL, were evaluated by Cox regression analysis, Kaplan Meier method and log-rank test., Results: A total of 8023 HIV+ pts (82% males, median age at first pos anti-HIV test 36 years, IQR: 29-44) were included: 6214 (77.5%) started ART during the study period. Women, people who inject drugs (PWID) and residents in Southern Italy presented the lowest levels of education and the highest rate of unemployment compared to other groups. Females, pts aged > 50 yrs., unemployed vs employed, and people with lower educational levels presented the lowest CD4 count at ART initiation compared to other groups. The overall median time to ART initiation was 0.6 years (yrs) (IQR 0.1-3.7), with a significant decrease over time [2002-2006 = 3.3 yrs. (0.2-9.4); 2007-2011 = 1.0 yrs. (0.1-3.9); 2012-2016 = 0.2 yrs. (0.1-2.1), p < 0.001]. By multivariate analysis, females (p < 0.01) and PWID (p < 0.001), presented a longer time to ART initiation, while older people (p < 0.001), people with higher educational levels (p < 0.001), unemployed (p = 0.02) and students (p < 0.001) were more likely to initiate ART. Moreover, PWID, unemployed vs stable employed, and pts. with lower educational levels showed a lower 1-year probability of achieving HIV-RNA suppression, while females, older patients, men who have sex with men (MSM), unemployed had higher 1-year risk of first-line ART discontinuation., Conclusions: Despite median time to ART start decreased from 2002 to 2016, socio-demographic factors still contribute to disparities in ART initiation, outcome and durability.

Background: The wide offer of information on pharmaceuticals does not often fulfill physicians' needs: problems of relevance, access, quality and applicability are widely recognized, and doctors often rely on their own experience and expert opinions rather than on available evidence. A quali-quantitative research was carried out in Italy to provide an overview on information seeking behavior and information needs of doctors, in particular of infectious disease specialists, and to suggest an action plan for improving relevance, quality and usability of scientific information., Methods: We did a quantitative survey and three focus groups. Two hundred infectious disease specialists answered a 24-item questionnaire aimed at investigating features of scientific information they receive and their ratings about its completeness, quality and usability. Subsequent focus groups, each involving eight specialists, investigated their opinions on information sources and materials, and their suggestions on how these could better support their information needs., Results: The quantitative survey indicated doctors' appreciation of traditional channels (especially drug representatives) and information materials (brochures), but also their attitude to autonomous search of information and their wish to have more digital channels available. Focus groups provided more depth and, not surprisingly, revealed that physicians consider critical to get complete, comparative and specific information quickly, but also that they would like to discuss their doubts with expert colleagues. Quite strikingly, limited concerns were expressed on information validity, potential biases and conflicts of interests, as scientific validity seems to be related to the perceived authoritativeness of information sources rather than to the availability of a transparent evaluation framework. Although this research investigated views of infectious disease specialists, we believe that their opinions and perceived needs should not substantially differ from those of other clinicians, either in primary or in secondary care., Conclusions: In participants' view, the ideal information framework should provide quick and tailored answers through available evidence and favor the exchange of information between practitioners and trusted experts. The general consensus existing within the scientific and medical community on the need for integrating available evidence and experience is confirmed, although the issues of information validity and conflicts of interests seem definitely overlooked.

Whilst renal dysfunction, especially mild impairment (6090, 60-89, <60 ml/min, was 2.91 (95% CI 2.30-3.67), 4.63 (95% CI 3.51-6.11) and 11.9 (95% CI 6.19-22.85) per 1,000 PYFU respectively, with an unadjusted hazard ratio (HR) of 4.14 (95%CI 2.07-8.29) for patients with eGFR <60 ml/min and 1.58 (95%CI 1.10-2.27) for eGFR 60-89 compared to those with eGFR ≥90. Of note, these estimates are adjusted for traditional cardio-vascular risk factors (e.g. smoking, diabetes, hypertension, dyslipidemia). Incidence of AIDS-related events was 9.51 (95%CI 8.35-10.83), 6.04 (95%CI 4.74-7.71) and 25.0 (95%CI 15.96-39.22) per 1,000 PYFU, among patients with eGFR >90, 60-89, <60 ml/min, respectively, with an unadjusted HR of 2.49 (95%CI 1.56-3.97) for patients with eGFR <60 ml/min and 0.68 (95%CI 0.52-0.90) for eGFR 60-89. The risk of AIDS events was significantly lower in mild renal dysfunction group even after adjustment for HIV-related characteristics. Our data confirm that impaired renal function is an important risk marker for CCVD events in the HIV-population; importantly, even those with mild renal impairment (90

The efficacy data obtained with boceprevir and telaprevir for persons with hepatitis C virus (HCV) genotype 1 infection raise the question of whether HCV protease inhibitors should be used in human immunodeficiency virus (HIV)/HCV co-infected persons. The Italian Association for the Study of Infectious and Tropical Diseases has made these recommendations to provide the rationale and practical indications for the use of triple anti-HCV therapy in persons living with HIV (PLWHIV). A Writing Committee of experts indicated by the President of the Association and a Consulting Committee con- tributed to the document. The final draft was submitted to the evaluation of external experts and the text modified according to their suggestions and comments. Treatment of HCV co-infection should be considered for all HCV RNA positive PLWHIV. Response-guided therapy with pegylated interferon and ribavirin is the standard treatment of PLWHIV with infection by HCV genotype 2, 3, 4, 5 and 6. Boceprevir and telaprevir should be used to treat HCV genotype 1 infection in HIV/HCV co-infected patients for 48 weeks on an individual basis, with close monitoring of their efficacy and tolerability with concur- rent antiretroviral therapy, taking into account potential drug-drug interactions. The decision to treat a patient or to wait for better treatment options, or to discontinue treatment should be made on an individual basis taking into account pre-treatment variables and the on-treatment HCV RNA kinetics.

Objectives: Evaluate gender differences with regard to baseline characteristics and outcome of therapy in cohorts of the SCOLTA (surveillance cohort long-term toxicity of antiretrovirals) project., Methods: The SCOLTA project is an active pharmacovigilance system for new antiretroviral drugs. Since 2002, patients were enrolled in nine cohorts (lopinavir, tenofovir, atazanavir, fosamprenavir, enfuvirtide, tipranavir, darunavir, raltegravir and maraviroc)., Results: Two thousand one hundred and fifty-four patients were included in 5 PI cohorts; 607 (28.2%) were female. Women were younger and less frequently HCV-coinfected than men. At study entry, they were less frequently in CDC stage C, but CD4+ cells/mm(3) and detectable HIV-RNA were not different by gender. Women had triglycerides alterations less frequently than men, but showed a higher proportion of low HDL-cholesterol. Women were protected from incident grade 2-4 triglycerides increase (odds ratio=0.39, 95% confidence interval 0.18-0.88; P=0.02). Mean CD4+ cell count increased in both men and women; despite a non-significantly lower initial CD4+ level, women had a better immunological recovery. Women discontinued PI treatment for adverse events and their own will more frequently., Conclusions: In these cohorts, gender distribution mirrored the Italian HIV population. Women were younger than men when they started their first ARV therapy and when they entered our cohorts. On the same treatment, they had a better immune response, though no significant difference emerged on virologic control and treatment durability. As compared to men, women appeared at lower risk of hypertriglyceridaemia. They stopped PI-based treatment of their own will more frequently than men, suggesting the need for a focused effort on adherence., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Cardiovascular risk profile was compared in 765 Italian HIV-infected outpatients enrolled in 2005 and in 765 individually age-matched and sex-matched patients enrolled in 2011. Median Framingham risk score was 8.6% in 2005 vs. 7.9% in 2011 (P = 0.04); metabolic syndrome was present in 40.3% vs. 33.4% (P = 0.006). Blood glucose, triglycerides, prevalence of smokers, and lipodystrophy were all significantly lower in 2011 (all P < 0.0001). Cardiovascular risk improved over a 6-year period in Italian HIV-infected patients.

Objective: To evaluate safety and durability of once-daily and twice-daily darunavir/ritonavir (DRV/r)-based treatment in HIV patients in clinical practice., Methods: The Surveillance Cohort Long-Term Toxicity Antiretrovirals (SCOLTA) project is a prospective, observational, multicenter cohort created to assess the incidence of adverse events in patients receiving new antiretroviral drugs. Twenty-five Italian infectious diseases centers enroll patients and collect their data through this on-line system. Periodical evaluations of these patients, including physical examination and laboratory tests, were performed at baseline and every 6 months., Results: Four hundred and twenty-nine patients were enrolled since May 2006. Eighty-five patients (19.8%) were prescribed once-daily DRV/r; 31 of them were treatment-naïve (36.5%). Among 54 (63.5%) treatment-experienced patients, 21 (38.9%) had undetectable viral load and started once-daily DRV/r as a simplification regimen. Patients on twice-daily regimen were older, more frequently lipodystrophic, HCV-coinfected, and in CDC stage C. In the following 24 months of follow-up, the viral load steadily decreased as well as the CD4 cell count rose. The reason for discontinuation did not significantly differ between groups. Mean blood glucose (BG) change from baseline did not show significant difference between groups, as well as high density lipoprotein cholesterol (HDL-C), triglycerides (TGL) and alanine transaminase (ALT). The survival curve shows that patients in the once-daily regimen withdrew treatment more frequently than those on twice-daily regimen (Log Rank Chi(2)P=0.009)., Conclusion: Our study showed that DRV/r administrated both once daily or twice daily was safe and well tolerated with few discontinuations due to adverse events., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Objective: To estimate the lifetime cost utility of two antiretroviral regimens (once-daily atazanavir plus ritonavir [ATV+r] versus twice-daily lopinavir/ritonavir [LPV/r]) in Italian human immunodeficiency virus (HIV)-infected patients naïve to treatment., Design: With this observational retrospective study we collected the clinical data of a cohort of HIV-infected patients receiving first-line treatment with LPV/r or ATV+r., Methodology: A Markov microsimulation model including direct costs and health outcomes of first- and second-line highly active retroviral therapy was developed from a third-party (Italian National Healthcare Service) payer's perspective. Health and monetary outcomes associated with the long-term use of ATV+r and LPV/r regimens were evaluated on the basis of eight health states, incidence of diarrhoea and hyperbilirubinemia, AIDS events, opportunistic infections, coronary heart disease events and, for the first time in an economic evaluation, chronic kidney disease (CKD) events. In order to account for possible deviations between real-life data and randomised controlled trial results, a second control arm (ATV+r 2) was created with differential transition probabilities taken from the literature., Results: The average survival was 24.061 years for patients receiving LPV/r, 24.081 and 24.084 for those receiving ATV+r 1 and 2 respectively. The mean quality-adjusted life-years (QALYs) were higher for the patients receiving LPV/r than those receiving ATV+r (13.322 vs. 13.060 and 13.261 for ATV+r 1 and 2). The cost-utility values were 15,310.56 for LPV/r, 15,902.99 and 15,524.85 for ATV+r 1 and 2., Conclusions: Using real-life data, the model produced significantly different results compared with other studies. With the innovative addition of an evaluation of CKD events, the model showed a cost-utility value advantage for twice-daily LPV/r over once-daily ATV+r, thus providing evidence for its continued use in the treatment of HIV.

The polycyclic synthetic musks (PCMs) such as galaxolide (HHCB), tonalide (AHTN) and celestolide (ABDI) are important ingredients in fragrances for consumer products because of their typical musky scent. In EU, PCMs are classified as HPVC (High Production Volume Chemicals). Furthermore, it has been recognized that these substances are only partially degraded in domestic sewers. For both reasons these chemicals are considered ubiquitous contaminants of aquatic systems. Monitoring data are available for the Northern region of the EU, but it is not known whether they are also representative for the Southern EU countries. The lack of data upon the environmental exposure in Southern EU can be significant, since use patterns and volumes differ from country to country. This is particularly true for Italy that has the largest detergent consumption per capita in EU. Due to this, the objective of the present study was to investigate the occurrence of selected PCMs in the Molgora River (Lombardia region, Italy). To our knowledge it represents the first overview of PCM occurrence in the Italian water bodies. Water samples were collected seasonally in seven sampling stations located before and after the 3 sewage treatment plants present along the river, which serve about 300,000 inhabitants. The spatial and temporal profiles of contamination are described. A comparison of the results with existing monitoring data of other European regions indicated a significant higher level of PCM pollution of the Molgora River and the need to extend the monitoring campaigns to other Italian water bodies, in order to achieve a better knowledge of the levels of PCM contamination in this country., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Healthcare expenditures incurred by the Health Service for HIV-infected patients have not been reported in Italy., Objective: To present health care costs for HIV-infected patients in the Lombardy Region, in 2004-2007, to determine the clinical characteristics of HIV infection associated with costs., Methods: Retrospective, observational, budget impact study, based on information collected for the period 2004-2007, including hospitalizations, outpatient services, highly active antiretroviral therapy (HAART) and non-HAART drug utilization. Inclusion criteria includes: confirmed HIV infection, age ≥18 years, resident in Lombardy Region, and followed at the "L. Sacco" Hospital in Milan from 2004 to 2007., Results: The mean total cost per year to provide healthcare to HIV-positive patients was rather stable (€ 9658.36 in 2004 and € 9745.65 in 2007 (+0.90%)); HAART represented more than 60% of the total cost. We found that hepatitis C virus coinfection was related to higher costs (€ 11,003.45 vs. € 8896.06), as well as CD4 cell count <200 cells/mm (€ 12,681.36 vs. € 9594.11 and € 9450.36 in 200-499 and ≥500 cells/mm, respectively). The mean total cost of HIV health care was higher in patients who initiated antiretroviral treatment before 1997 than in those who started after 1996., Conclusions: The mean total cost per year to provide health care to HIV-positive patients was stable during the period 2004-2007, with an increase of HAART percentage impact on the total cost. Several clinical characteristics of HIV-infected patients were significantly associated with cost variation.

In this paper, in an attempt to reveal possible changes connected to natural or anthropogenic causes, the main results of hydrogeochemical monitoring carried out at Mount Etna are evaluated. We report on the salinity contents of the groundwaters that flow in fractured volcanics, which make up the flanks of the volcano. These waters, analyzed for major ion chemistry, were sampled regularly from 1994 to 2004. Basing on nonparametric Sen's slope estimator, time series of groundwater composition reveal that the salinity of most of the Etnean aquifers increased by 0.5% to 3.5% each year during this period. This change in the water chemistry is clearly referable to the overexploitation of the aquifers. This increasing trend needs to be inverted urgently; otherwise, it will cause a shortage of water in the near future, because the maximum admissible concentration of salinity for drinking water will be exceeded.

Objective: To identify and characterize HIV-infected patients at higher cardiovascular risk in ordinary clinical settings., Design: Multicenter, nationwide cross-sectional study., Methods: Consecutive HIV-patients, attending scheduled visits at facilities involved in the Italian coordination group for the study of allergies and HIV infection (CISAI), were included between February and April, 2005. Their 10-year probability of acute coronary events was calculated using the Framingham Risk Score (FRS) as well as 3 other cardiovascular algorithms ("PROCAM", "PROGETTO CUORE", "SCORE"); Metabolic Syndrome (MS) was diagnosed according to the National Cholesterol Education Program definitions. An estimated 10-year CVD >or=10% and/or MS led to the diagnosis of high CV risk. We compared selected clinical features between high- and low-risk patients., Results: A total of 1230 HIV infected patients (72% males, mean age of 43+/-9 years), 185 of whom treatment-naive, were evaluated. FRS gave the highest estimate of CV risk. The mean 10-year risk for acute coronary events according to FRS was 7.4+/-7.0. MS was present in 22% of the observed patients. Accordingly, 443 patients (36%) were classified at high risk. Twelve percent of the patients (n=142) had both a FRS >or=10% and a diagnosis of MS. The main single predictor of increased cardiovascular risk was smoking (60% of whole sample). A higher prevalence of clinically evident lipodystrophy and a higher CD4 T-cell counts were found both in patients with higher FRS and in patients with high FRS and MS (both p<0.001)., Conclusions: The worst estimation of CV risk was obtained with the FRS algorithm. Clinical evidence of lipodystrophy and higher CD4 T-cell counts were closely associated to a worse cardiovascular risk profile.

Objective: To evaluate the prevalence and incidence of nephrotoxicity in HIV-infected patients enrolled in the SCOLTA Project tenofovir cohort and to identify possible risk factors., Design: The SCOLTA Project is a prospective, observational, multicenter study involving 25 infectious disease departments in Italy created to assess the incidence of severe adverse events in patients receiving new antiretroviral drugs., Patients: The SCOLTA Project tenofovir cohort includes a total of 754 HIV infected patients., Results: Data including grade II-IV creatinine elevations according to ACTG scale were available in 354 patients, 237 (67%) males with a mean age of 40.1+/-7.6 years enrolled in the SCOLTA Project tenofovir cohort. During a mean follow up of 19.5+/-11.5 months creatinine elevations were reported in 9/354 (2.5%) patients, all males. Mean duration of tenofovir therapy at the event was 9.5+/-5 months. The overall incidence was 1.6 (95% CI 1.5-1.7) per 100 person-years (p-y) and 0.5 (95% CI 0.4-0.6) p-y for grade III. No grade IV creatinine elevations were reported. Patients with nephrotoxicity were older and more frequently male, HCV infected, in CDC stage C and their CD4 cell count was significantly lower than those without nephrotoxicity. No significant difference was found between tenofovir co-administered antiretroviral drugs., Conclusions: Both prevalence and incidence of nephrotoxicity were low in patients receiving tenofovir in a non-selected clinical setting. Renal injury in patients receiving tenofovir seems associated with the presence of co-morbidities and with advanced HIV infection.

The present document contains recommendations for assessment, prevention and treatment of cardiovascular risk for HIV-infected patients. All recommendations were graded according to the strength and quality of the evidence and were voted on by 73 members of the Italian Cardiovascular Risk Guidelines Working Group which includes both experts in HIV/AIDS care and in cardiovascular and metabolic medicine. Since antiretroviral drug exposure represents only one risk factor, continued emphasis on an integrated management is given. This should include prevention and treatment of known cardiovascular risk factors (such as dyslipidaemia, diabetes, insulin resistance, healthy diet, physical activity, avoidance of smoking), but also rational switch of antiretroviral drugs. A rational switch strategy should consider both metabolic and anthropometric disturbances and effectiveness of antiretroviral regimens.

The SCOLTA project (Surveillance Cohort Long-term Toxicity Antiretrovirals) is a system for online surveying of adverse reactions to recently commercialized antiretroviral drugs and a "sentinel" for unexpected and late adverse reactions arising during any antiretroviral treatment (available at: http://www.cisai.info). To date, 25 Italian departments of infectious diseases have participated at the project. The New Drugs Project is a prospective, multicenter, observational pharmacovigilance study involving 1 cohort of patients for each new drug. All patients who were consecutively started on lopinavir (LPV), tenofovir (TDF), peginterferon (IFN), atazanavir (ATZ), enfuvirtide (T-20), and tipranavir (TPV) were enrolled. All grade III or IV adverse events (according to the AIDS Clinical Trials Group definitions) are reported on the web site. The Unexpected Events Project identifies unexpected adverse reactions during treatment and reports them. This paper presents the preliminary findings for the New Drugs Project. Between October 1, 2002, and March 30, 2004, 1184 patients were enrolled. The lopinavir/ritonavir (LPV/r) cohort comprises 703 patients, the TDF cohort 585, IFN 35, ATZ 95, T-20 10, and TPV 8. So far 100 grades III and IV adverse events have been reported, 73 in the LPV/r group. In this cohort the rate of adverse events per 100 person-years was 14.2 on the basis of all patients treated, 9.8 for treatment-naive patients, and 15 for treatment-experienced patients. These findings, though preliminary, show that this data collection method gives timely real-life information from which to assess the impact of short- and long-term toxicity of new antiretroviral drugs.

Hepatitis C virus common transmission routes and HCV coinfection is frequent in persons living with HIV. Liver enzyme elevation following the initiation of antiretroviral therapy is frequently seen in HIV-infected patients with chronic liver disease, particularly those with chronic hepatitis C. This complication may lead to treatment discontinuation, complicating HIV therapeutic management. Multiple factors influence the risk of liver toxicity under antiretroviral therapy, including the specific drug in use (e.g. use of full doses of ritonavir), and environmental factors (e.g. alcohol abuse). However a beneficial effect of antiretroviral therapy on liver disease has been supported by some studies. Despite increasing knowledge of HCV/HIV coinfection, there is no clear consensus on how to treat HIV in HCV-coinfected patients An Italian group of experts were invited to discuss in detail the current risks and implications of antiretroviral treatment in HIV-infected persons with chronic hepatitis C, and their main conclusions are summarized in this consensus document.