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The “chronicization” of HIV infection brings about a growing necessity to attentively evaluate current and potential complications when prescribing the individual therapeutic regimen. Starting from this need, we developed two HIV-comorbidity simulators that, basing on the evidence available in medical literature and starting from the current clinical and demographic features of the individual patient, project and compare the risks of developing and worsening of nephropathy and osteopathy associated with possible ARV regimens. These simulators are embedded in a desktop, user-friendly software thought to be used by the treating physician during prescription discussion with his/her patients, in order to highlight expected clinical outcomes and healthcare resource consumption that may differ according to the therapeutic strategy selected. In this article we present the sources and methods used in developing the mathematical models, alongside a set of examples and the results of cohort-level validation runs.

Introduction Dementia is one of the major causes of disability and dependency among older people worldwide, and hospitalization occurs frequently in demented patients. The present study examined the course of behavioural symptoms and functional conditions in hospitalised older people with dementia. Materials and methods Prospective cohort study of 179 demented patients (age > 64 years) admitted to four geriatric units, evaluated at admission, discharge and at 6 months after discharge. An analysis of predictors of functioning improvement was performed. Results Patients with no symptoms at NeuroPsychiatric Inventory baseline assessment did not show any changes at both discharge and follow-up, while patients with symptoms at baseline showed an improvement in every subscale from admission to discharge. Using Barthel Index as a measure of functioning, we found a significant improvement in both "admission-discharge" and "discharge-follow-up" timeframe for the most impaired patients. However, for the less impaired patients, no significant changes emerged from admission to discharge, while a significant worsening occurred from discharge to follow-up. The significant associated variables with improvement in Barthel Index from discharge to follow-up were age and Blaylock Risk Assessment Screening Score at admission. Conclusion Interesting trends in the course of hospitalized older patients with dementia have been found, and they were associated to different levels of functional impairment at admission. Further research is still needed to understand the predictors of improvement and worsening in such hospitalized patients.

Hepatitis C virus (HCV) infection is now considered a systemic disease due to the occurrence of extra-hepatic manifestations. Among these, the renal involvement is frequent. HCV infection, in fact, is strongly associated with proteinuria and chronic kidney disease (CKD) and negatively affects the prognosis of renal patients. In the last few years, availability of more specific and effective drugs against HCV has dramatically changed the clinical course of this disease. These drugs may provide further advantages in the CKD population as a whole by reducing progression of renal disease, mortality rate and by increasing the survival of graft in renal transplant recipients. The strict pathogenetic and prognostic link between HCV infection and CKD requires an ongoing relationship among the healthcare professionals involved in the treatment of both HCV infection and CKD. Therefore, Scientific Societies involved in the care of this high-risk population in Italy have organized a joint expert panel. The aim of the panel is to produce a position statement that can be used in daily clinical practice for the management of HCV infected patients across the whole spectrum of renal disease, from the conservative phase to renal replacement treatments (dialysis and transplantation). Sharing specific evidence-based expertise of different professional healthcare is the first step to obtain a common ground of knowledge on which to instate a model for multidisciplinary management of this high-risk population. Statements cover seven areas including epidemiology of CKD, HCV-induced glomerular damage, HCV-related renal risk, staging of liver disease in patients with CKD, prevention of transmission of HCV in hemodialysis units, treatment of HCV infection and management of HCV in kidney transplantation.

The aims of this study were (a) to investigate the presence of clinically significant personality traits and personality disorders (PD) in patients living in residential facilities, with or without a history of violence (69 and 46, respectively); and (b) to investigate any associations between clinically significant personality traits and PDs, aggression, impulsivity, hostility, and violent behavior during a 1-year follow-up. The most frequent primary diagnoses were schizophrenia (58.3%) and PD (20.9%). Those with a history of violence demonstrated more antisocial and alcohol dependence features and lower depressive PD symptoms than the control group. Hostility levels, antisocial symptoms, and drug dependence, as well as a Structured Clinical Interview for DSM-IV Axis II diagnosis of PD, predicted aggressive and violent behavior during follow-up. The study confirms the relevance of assessing PDs both to evaluate the risk of violent behavior and to plan appropriate preventive and treatment intervention.

The introduction of tenofovir (TFV) alafenamide (TAF) into clinical practice will be a further revolution in antiretroviral therapy. Currently available HIV-1 regimens are wide enough to allow diversified usage in different settings. Despite the fact that TAF is not capillary accessible, even in industrialized countries, ultimate International Guidelines have already included TAF in backbone or in single-tablet regimens. Due to a better safety profile, TAF will progressively replace TFV disoproxil fumarate, both in naïve and experienced patients. However, therapeutic innovations have to deal with budget constraints and different global spending-review patterns. The aim of this article is to give a comprehensive agenda of TAF use in naïve and experienced HIV-1 infected patients, providing a full review of the studies present in the literature and contextualizing these findings into daily clinical practice.

The relationship between hepatic tolerance and hepatitis C virus (HCV) co-infection has not been extensively studied in clinical practice. We assessed the efficacy and safety of raltegravir-based therapy in an Italian cohort of HIV/HCV co-infected patients. One hundred and forty patients with HIV/HCV co-infection initiating raltegravir from SCOLTA project (Surveillance Cohort Long-Term Toxicity Antiretrovirals) were examined. Of them, 43 were women, with mean age of 45.4. ±. 6.4. years; 65 (46%) had undetectable HIV-RNA. < 50. copies/mL and 75 (54%) HIV-RNA. ≥. 50. copies/mL. According to CDC classification, 49 (35%) were in stage C. Based on Fib4 score at the time of starting raltegravir, patients were classified in class I in 41 cases, class II in 68 and in class III in 31 cases. Globally, the Fib4 score slightly decreased during 24. months follow-up, from 2.2 to a value of 1.8. Hepatic adverse events of any grade were observed in 67 patients, of which only 2 cases (3%) had severe liver toxicity (grade 3-4). Only one patient had to discontinue the therapy because of adverse events. According to univariate analysis, being in CDC stage C represented a risk for the development of liver toxicity, with a hazard ratio (HR) of 2.27 (95% CI 1.06-4.84, P= 0.033). None of the other variables considered (age, sex, years since detection of HIV and HCV-RNA detectable, years of previous HIV therapy, concomitant therapy with PI or NRTI, CD4+ cell count, Fib4, and transaminases level at baseline) resulted statistically correlated to the outcome. In conclusion, raltegravir-based regimens can be safely used in HCV infected patients; in this study, the hepatic toxicity has been found to be more frequent in patients with an advanced HIV disease (CDC stage C), independently of HIV-RNA suppression at raltegravir initiation.

Background and aims PREVALEAT (PREmature VAscular LEsions and Antiretroviral Therapy) II is a multicenter, longitudinal cohort study aimed at the evaluation of cardiovascular risk among advanced HIV-positive, treatment-naive patients starting their first therapy. We hypothesized that these patients, present a higher cardiovascular (CV) risk. Methods The study included all consecutive naive patients with less than 200 CD4 cells/ml starting antiretroviral therapy. Our primary objective was to evaluate changes in carotid intima- media thickness (IMT). Secondary endpoints included changes in flow mediated vasodilation (FMD), inflammatory markers, triglycerides and cholesterol. Patients were evaluated at time 0, and after 3, 6 and 12 months. Results We enrolled 119 patients, stratified into three different groups: patients receiving atazanavir/ritonavir boosted (ATV/r) based regimens, efavirenz (EFV) based regimens and darunavir/ritonavir boosted (DRV/r) based regimens. At baseline, advanced naive patients showed a relevant deterioration of CV conditions in terms of traditional CV risk factors, endothelial dysfunction and serum biomarkers. During the 12-month follow up period, mean blood lipids significantly increased: total cholesterol from 159 to 190 mg/dL, HDL-C from 31 to 41 mg/dL, and LDL-C from 99 to 117 mg/dL. D-dimers steadily decreased (median level 624 at baseline and 214 at T3), whereas ICAM and VCAM consistently raised. DRV/r and ATV/r determined a more marked decrease of D-dimers as compared to EFV. Regarding the epi-aortic changes (IMT >1 mm or presence of atherosclerotic plaques), patients in the DRV/r group were at risk of developing pathological IMT during the study (OR 6.0, 95% CI 0.9–36.9), as compared to EFV ones. Conclusions CV risk was elevated in advanced naive patients and tended to remain high in the first year of therapy.

Background Aim of this review is to focus the attention on people living with HIV infection at risk of developing a cardiovascular event. What is or what would be the most suitable antiretroviral therapy? Which statin or fibrate to reduce the risk? How to influence behavior and lifestyles? Discussion Prevention of cardiovascular disease (CVD) risk remains the first and essential step in a medical intervention on these patients. The lifestyle modification, including smoking cessation, increased physical activity, weight reduction, and the education on healthy dietary practices are the main instruments. Statins are the cornerstone for the treatment of hypercholesterolemia. They have been shown to slow the progression or promote regression of coronary plaque, and could also exert an anti-inflammatory and immunomodulatory effect. However the current guidelines for the use of these drugs in general population are dissimilar, with important differences between American and European ones. The debate between American and European guidelines is still open and, also considering the independent risk factor represented by HIV, specific guidelines are warranted. Ezetimibe reduces the intestinal absorption of cholesterol. It is effective alone or in combination with rosuvastatin. It does not modify plasmatic concentrations of antiretrovirals. A number of experimental new classes of drugs for the treatment of hypercholesterolemia are being studied. Fibrates represent the first choice for treatment of hypertriglyceridemia, however, the renal toxicity of fibrates and statins should be considered. Omega 3 fatty acids have a good safety profile, but their efficacy is limited. Another concern is the high dose needed. Other drugs are acipimox and tesamorelin. Current antiretroviral therapies are less toxic and more effective than regimens used in the early years. Lipodistrophy and dyslipidemia are the main causes of long-term toxicities. Not all antiretrovirals have similar toxicities. Protease Inhibitors may cause dyslipidemia and lipodystrophy, while integrase inhibitors have a minimal impact on lipids profile, and no evidence of lipodystrophy. There is still much to be written with the introduction of new drugs in clinical practice. Conclusions Cardiovascular risk among HIV infected patients, interventions on behavior and lifestyles, use of drugs to reduce the risk, and switch in antiretroviral therapy, remain nowadays major issues in the management of HIV-infected patients.

The increased risk of violence in schizophrenia has been linked to several environmental, clinical and neuropsychological factors, including executive dysfunction. However, data about the nature of these effects are mixed and controversial. The main aim of this study was to investigate the relationship between clinical and neuropsychological factors with violence risk in patients with schizophrenia, taking into account current psychopathology and lifetime alcohol use. We compared a sample of patients living in Residential Facilities (RFs) with schizophrenia and a past history of interpersonal violence (vSZ, N = 50) to patients with schizophrenia matched on age, gender and alcohol abuse/dependence but with no violence history (nvSZ, N = 37). We then established the association between the clinical and neuropsychological factors that predicted violence over a 1 year follow-up period. The results revealed that vSZ patients living in RFs were characterized by greater compulsory hospital admissions, higher anger and less negative symptoms as compared to nvSZ patients. vSZ patients performed better on executive and motor tasks than nvSZ; however, these differences appeared to be explained by the lower negative psychotic symptom in the vSZ group. Both groups were involved in episodes of violence during the follow-up period; among the two, the vSZ patients were more likely to be violent. Negative symptoms predicted less verbal aggression at 1 year follow-up. Overall, these findings support a key role of negative rather than positive symptoms in driving violence risk among SZ patients living in RFs, in a manner that negative symptoms are linked to a lower risk of violence.

Background: Hypertension control is often inadequate in HIV patients. In a contemporary, nationwide cohort of Italian HIV-infected adults, we assessed time trends in hypertension prevalence, awareness, treatment, and control. We also evaluated predictors of cardiovascular events and of new-onset hypertension. Methods: Multicenter prospective cohort study, sampling 961 consecutive HIV patients (71% men, mean age 46 ± 9 years, 30% hypertensive) examined in 2010-2014 and after a median follow-up of 3.4 years. Results: Among hypertensive patients, hypertension awareness (63% at baseline and 92% at follow-up), treatment (54 vs. 79%), and control (35 vs. 59%) all improved during follow-up. The incidence of new-onset hypertension was 50.1/1000 person-years (95% confidence interval, 41.2-60.3). Multivariable-adjusted predictors of hypertension were age, BMI, estimated cardiovascular risk, blood pressure, and advanced HIV clinical stage. In total, 35 new cardiovascular events were reported during follow-up (11.1/1000 person-years). In a multivariate model, baseline cardiovascular risk and hypertensive status predicted incident cardiovascular events, whereas a higher CD4 cell count had a protective role. In treated hypertensive patients, the use of integrase strand transfer inhibitors at follow-up was associated with a lower SBP (average yearly change,-3.8 ± 1.6 vs.-0.9 ± 0.5 mmHg in integrase strand transfer inhibitor users vs. nonusers, respectively, P = 0.02). Conclusion: Hypertension awareness, treatment, and control rates all improved in adult Italian HIV patients over the last few years, although hypertension remains highly prevalent (41%) in middle-aged HIV patients, and significantly impacts cardiovascular morbidity. Traditional risk factors and advanced HIV disease predict new-onset hypertension, whereas CD4 cell count favorably affects future cardiovascular events.

Objectives- To investigate common carotid intima-media thickness in a cohort of patients who were vertically infected with human immunodeficiency virus 1 (HIV-1). Methods- We conducted a cross-sectional observational study. Human immunodeficiency virus 1-infected patients were compared with age-, sex-, and body mass index-matched healthy participants. Common carotid intima-media thickness was measured in all participants on both sides of the neck, and the mean intima-media thickness was calculated. Metabolic parameters and markers of inflammation were measured only in HIV-1-infected patients. Statistical analysis was performed by multiple regression and by a matrix of Pearson correlation coefficients. The Student t test was used to compare mean common carotid intima-media thickness values between groups. Results- Forty patients (21 female) with HIV-1 infection acquired from birth with a mean age ± SD of 16.3 ± 4.7 years and 27 healthy participants (11 female) with a mean age of 17.7 ± 4.6 years were included in the study. Mean common carotid intima-media thickness in the HIV-1-infected group (0.450 ± 0.088 mm) was significantly higher (P < .05) than in the control group (0.407 ± 0.079 mm). No significant association was found between intima-media thickness and a specific antiretroviral regimen, exposure to combined antiretroviral agents, and HIV status. In multiple regression analyses, higher levels of insulin (P= .007) and elevated levels of glycated hemoglobin (P= .01) were associated with intima-media thickness changes. Conclusions- Patients perinatally infected with HIV have increased common carotid intima-media thickness compared with healthy individuals. These changes were more pronounced with increasing age and inflammation markers. Interventions that improve cardiovascular risk profiles should be considered in HIV-infected young adults.

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 Chi2 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. © 2013 Elsevier Masson SAS.

Objective: HIV infection has been associated with increased cardiovascular risk. Twenty-four-hour ambulatory blood pressure (BP) is a more accurate and prognostically relevant measure of an individual's BP load than office BP, and the ambulatory BP-derived ambulatory arterial stiffness index (AASI) and symmetric AASI (s-AASI) are established cardiovascular risk factors. Methods: In the setting of the HIV and HYpertension (HIV-HY) study, an Italian nationwide survey on high BP in HIV infection, 100 HIV-infected patients with high-normal BP or untreated hypertension (72% men, age 48 ± 10 years, BP 142/91 ± 12/7 mmHg) and 325 HIV-negative individuals with comparable age, sex distribution, and office BP (68% men, age 48 ± 10 years, BP 141/90 ± 11/8mmHg) underwent 24-h ambulatory BP monitoring. Results: Despite having similar office BP, HIV-infected individuals had higher 24-h SBP (130.6 ± 14 vs. 126.4 ± 10 mmHg) and pulse pressure (49.1 ± 9 vs. 45.9 ± 7mmHg, both P < 0.001), and a lower day-night reduction of mean arterial pressure (14.3 ± 9 vs. 16.3 ± 7%, P = 0.025). Both s-AASI and AASI were significantly higher in HIV patients (s-AASI, 0.22 ± 0.18 vs. 0.11 ± 0.15; AASI, 0.46 ± 0.22 vs. 0.29 ± 0.17; both P

Aim To evaluate, in human immunodeficiency virus-hepatitis C virus co-infected patients, the impact of C-C chemokine receptor type 5 (CCR5) antagonist maraviroc-based antiretroviral therapy on the carotid intima media thickness and on atheromasic plaques. Patients and methods In this pilot prospective study, 12 HIV-HCV co-infected patients underwent color-Doppler ultrasonography before and 48 weeks after switching to a dual therapy based on maraviroc plus protease inhibitors boosted with ritonavir. Changes of intima media thickness, inflammatory and endothelial adhesion biomarkers levels, Veterans Aging Cohort Study index and Framingham risk score were evaluated. Results At baseline 11 (91.6%) patients showed pathological ultrasonographic findings. After 48 weeks, two patients showed an amelioration of intima media thickness. Of the remaining patients with plaques, four showed a reduction of the previously diagnosed plaque; no patients worsened. Conclusion Our data suggest that CCR5 inhibition could reduce the development of atherosclerosis especially in the non-calcific stage and could play an important role in the blockade of atheromasic plaque progression.

Background and Aim Tenofovir disoproxil fumarate (TDF) is recommended as first-line monotherapy for nucleos(t)ide (NA)-naive chronic hepatitis B (CHB) patients and as a second-line rescue therapy for NA-experienced patients with a previous treatment failure. However, data regarding the efficacy of TDF monotherapy in patients with lamivudine resistance (LAM-R) successfully treated with LAM + adefovir (ADV) are limited. Herein, the efficacy and safety of switching from LAM + ADV to TDF monotherapy in clinical practice have been evaluated. Methods Sixty LAM-R HBeAg-negative CHB patients treated with ADV add-on therapy and stable viral suppression, were switched to TDF monotherapy and prospectively evaluated for virological response, liver and renal function, and bone mineral density. Results During a median period of 57 months of TDF monotherapy, all patients maintained a virological response, four of whom cleared HBsAg (6.6%) and discontinued treatment. Monitoring of renal function showed no case of the Fanconi syndrome, no significant alterations of median serum creatinine, eGFR and phosphate levels, although a reduction of TDF dosage was required in five patients (8.3%). Despite the stable virological suppression, five cirrhotic patients and one CHB patient developed hepatocellular carcinoma. Conclusions Our results demonstrate the efficacy of switching to TDF monotherapy in virologically suppressed CHB patients receiving long-term LAM + ADV therapy, with a low rate of adverse events.

Objectives: To investigate the use of statins and acetylsalicylic acid (ASA) in HIV people in clinical practice. Design: A multicenter, nationwide, prospective cohort study, including 1182 consecutive HIV patients was conducted. Methods: Statin and ASA prescription was evaluated in primary and secondary cardiovascular disease prevention, according to the European AIDS Clinical Society (EACS) guidelines. Results: Followed-up patients (998) were mostly males (70.9%) with a mean age at enrolment of 46.5years (SD 9.5). The mean time of follow-up was 3.3years (SD 0.8). At the last follow-up visit, statins would have been recommended for 31.2% and ASA for 16% by EACS guidelines. Conversely, only 15.6 and 7.6% of patients were on statin and ASA treatment, respectively; only 50.3% of patients treated with statins achieved recommended low-density lipoprotein cholesterol (LDL-c) levels. At the last follow-up visit, agreement between statin therapy and EACS recommendation was 0.58 (95% CI 0.52–0.63). The corresponding figure for ASA therapy was 0.50 (95% CI 0.42–0.58), whereas the agreement for ASA therapy in secondary prevention was 0.59 (95% CI 0.50–0.68). Conclusions: The prescription of statins and ASA in HIV-infected patients remains largely suboptimal, as only about 50% of patients requiring statins and ASA are properly treated. Higher attention on this relevant issue and further investigation are warranted in this at risk population.

HIV infection has been associated with increased risk of osteoporosis and fragility fractures. Dual-energy X-ray absorptiometry (DXA) is the reference standard to assess bone mineral density (BMD); however, it is not easily accessible in several settings. Heel Quantitative ultrasound (QUS) is a radiation-free, easy-to-perform technique, which may help reducing the need for DXA. In this cross-sectional study, we used heel QUS (Hologic Sahara®) to assess bone status in a cohort of HIV-infected patients. A QUS stiffness index (QUI) threshold >83 was used to identify patients with a low likelihood of osteoporosis. Moreover, we compared QUS results with those of 36 sex- and age-matched HIV-negative controls. 244 HIV-positive patients were enrolled. Median heel QUI value was 83 (73–96) vs. 93 (IQR 84–104) in the control group (p = 0.04). 110 patients (45 %) had a QUI value ≤83. Risk factors for low QUI values were age (OR 1.04 per year, 95 % CI 1.01–1.07, p = 0.004), current use of protease inhibitors (OR 1.85, CI 1.03–3.35, p = 0.039), current use of tenofovir (OR 2.28, CI 1.22–4.27, p = 0.009) and the number of risk factors for secondary osteoporosis (OR 1.46, CI 1.09–1.95, p = 0.01). Of note, QUI values were significantly correlated with FRAX score (r = −0.22, p = 0.004). According to EACS guidelines, 45 % of patients had risk factors for osteoporosis which make them eligible for DXA. By using QUS, we may avoid DXA in around half of them. As HIV-positive patients are living longer, the prevalence of osteoporosis is expected to increase over time. Appropriate screening, prevention and treatment are crucial to preserve bone health in this population. The use of screening techniques, such as heel QUS, may help reducing the need for DXA. Further studies are needed to define the diagnostic accuracy of this promising technique in the setting of HIV.

Objective HIV/hepatitis C virus (HCV) coinfected patients are usually considered a difficult-to-treat population. The aim of this study was to assess the effectiveness of telaprevir-based and boceprevir-based treatments with respect to the HIV status. Methods A prospective multicentre study was conducted among 22 Infectious Disease centres in Italy. Demographic, HIV and HCV related variables were collected, as well as data on HCV viral decay, sustained virologic response (SVR12) and grade 3-4 adverse events. Results Overall, 162 patients (24.7% HIV/HCV coinfected) received HCV treatment. Out of 145 evaluable patients, 57.2% achieved SVR12 (49.5% monoinfected, 78.9% coinfected). HIV coinfection was associated with a slight increase in the probability of SVR12 (adjusted odds ratio 1.66, 95% confidence interval 0.59-4.64, P =0.33). Premature discontinuation rates and adverse events were similar irrespective of HIV status, with the exception of skin reactions, which were more frequently in the HIV group. Conclusion In a real-life setting, with a high proportion of cirrhotic and treatment-experienced patients, the overall SVR12 rate was 57.2%. HIV coinfection was not associated with impaired outcome. Eur J Gastroenterol Hepatol 28:37-41.

Tenofovir disoproxil fumerate (TDF) is an effective nucleoside reverse transcriptase inhibitor for HIV infection but it is potentially nephrotoxic. A selective mithochondrial toxicity has been hypothesized. To assess early markers of renal toxicity, we evaluated a cohort of antiretroviral (ARV)-experienced HIV patients who had been switched from a thymidinic backbone to either a TDF/emtricitabine regimen (TDF; 73 patients) or an abacavir/lamivudine (ABV) regimen (28 patients). Markers of mitochondrial toxicity (cytochrome c, Cyc) or cytosolic (α-glutathione S transferase, α-GST) together with common indicators of renal damage were assessed at baseline (T0) and after 1 (T1), 3 (T2), 6 (T3), and 12 (T4) months of patient exposure to therapy. Clinical features of both groups were comparable at T0. There was no significant variation in estimated glomerular filtration rate (eGRF), median urine protein excretion, or microalbuminuria and serum phosphate levels in both groups during the study period. There was a significant increase in urinary excretion of phosphate in patients on TDF compared to those on ABV at T3 and T4. Fractional excretion of uric acid was also altered in the two treatment groups; there was no change in the ABV (constantly less than 0.10), but a progressive increase in TDF patients. Serum potassium levels were significantly lower in ABV than in TDF treated patients. Urine concentrations of α-GST showed a nonsignificant variation in both groups, while Cyc excretion was significantly higher at T1 and T3 in TDF-treated compared to ABV-treated patients. In conclusion, TDF may be associated with subclinical mitochondrial damage, inducing at a later stage increased urinary excretion of phosphate and uric acid, as markers of incipient tubular injury.

OBJECTIVE The purpose of this article is to assess the differences, if any, in the values of carotid artery stiffness parameters between HIV-infected subjects without known cardiovascular disease (CVD) or carotid artery plaques and HIV-uninfected control subjects matched for sex, age, body mass index, and other CVD risk factors (i.e., hypertension, hypercholesterolemia, diabetes, and cigarette smoking). Arterial stiffness is emerging as a predictor of CVD risk. By recording the blood pressure, an automated echo-tracking system implemented in ultrasound equipment allows evaluation of arterial stiffness. SUBJECTS AND METHODS Fifty-four HIV-infected patients without a history of CVD were closely matched for sex, age, body mass index, and CVD risk factors to 54 HIV-uninfected control subjects on an individual basis. Ultrasound studies of carotid artery stiffness parameters were performed using ultrasound equipment with a linear broadband high-frequency transducer. Carotid intima-media thickness was also measured. Repeatability between operators was assessed. Nonparametric Mann-Whitney U test, chi-square statistics, Fisher exact test, Pearson correlation coefficient, and intraclass correlation coefficient were used for statistical analysis. A p value less than 0.05 was considered statistically significant. RESULTS Except for arterial compliance in HIV-infected subjects, arterial stiffness parameters were correlated with age in both groups. Compared with matched control subjects, HIV-infected subjects showed lower arterial compliance parameter values (0.95 [interquartile range, 0.78-1.23] vs 0.76 [interquartile range, 0.62-1.00]; p = 0.0009), whereas other parameters were similar. Repeatability between operators was good. CONCLUSION HIV-infected subjects have an arterial compliance significantly lower than that of control subjects. The impairment of carotid artery distensibility may contribute to subclinical atherosclerosis.

To investigate skin blood flux and microvascular functional changes by laser Doppler flowmetry (LD) in patients with systemic sclerosis (SSc) at baseline and following dynamic stimulations.Skin blood flux of the dorsal hands was recorded by LD at baseline and after the cold test and the post-occlusive hyperemia test in 59 SSc patients (49 limited cutaneous, 10 diffuse cutaneous). Twenty-five patients with primary Raynaud's phenomenon (PRP), and 31 healthy donors (HD) were studied as controls.After the cold test, SSc patients had a significantly higher reduction of the blood flux (-38.4%+/-28) than PRP (-21.1%+/-37) and HD (-22.1%+/-23) subjects (p0.05). Within the SSc group, the cold test flux was significantly reduced in limited-SSc (-399%+/-28, p0.05), but not in diffuse-SSc (-31.2%+/-29), whereas, the time needed to recover the basal flux after the occlusive/ischemic test was significantly longer in diffuse-SSc (18.8s+/-21)than in limited-SSc (4.5s+/-4, p0.01) or HD (2.2s+/-2, p0.01) or PRP (0.4s+/-0.7, p0.01).These data clearly indicate an impairment of vascular tone regulatory mechanisms in SSc and suggest that a peculiar pathogenic mechanism may be involved in different SSc subset. Nevertheless, it has clear that PRP and SSc-associated RP have a distinct pattern at LD evaluation, and monitoring patients with PRP could be helpful to understand whether a change in the LD pattern might predict the development of SSc.

Various studies have been conducted to evaluate the role of antiretroviral therapy in the onset of cardiovascular risk among HIV-1-infected patients, while fewer data are available regarding antiretroviral-naïve patients. Our objective was to evaluate the cardiovascular risk among naïve subjects examining traditional risk factors, immunovirologic parameters, assessing the Framingham risk score (FRS), and detecting the presence of subclinical carotid lesions by means of color Doppler ultrasonography. One hundred seventy-two antiretroviral-naïve patients underwent color Doppler ultrasonography. An intima-media thickness (IMT) greater than 0.9 mm and/or atherosclerotic plaques were considered pathologic findings. Demographic, immunovirologic data, and risk factors for cardiovascular disease were collected. The 10-year probability of acute coronary events was assessed by the FRS. The statistical analysis was performed using t test and χ2, Fisher's test, and conditional multiple logistic. Thirty-six patients (20.9%) had lesions at ultrasonographic investigation. The presence of lesions was significantly related to male gender (p = 0.005), age (p = 0.003), sedentary life (p = 0.05), Centers for Disease Control and Prevention (CDC) group C or CD4+ less than 150 cells/mm3, and viral load (VL) > 100,000 copies per milliliter (p = 0.04). The presence of subclinical carotid lesions showed a highly significant direct association with the estimated FRS (p < 0.002). The presence of subclinical atheromasic lesion results was also high among antiretroviral- naïve patients. FRS is highly predictive of the lesions, but also an advanced stage of disease plays a significant role. Our data support the hypothesis that HIV infection per se is a risk factor for atherosclerosis. We recommend an ultrasonographic assessment both among patients with FRS 6% or more and among those in advanced stage of disease. © 2009 Mary Ann Liebert, Inc.

Several reports have indicated that patients with low CD4+ cell count could be at a higher risk for arterial lesions or cardiovascular disease (CVD). Recently, current use of abacavir has been associated with an excess risk of CVD. High sensitivity-C-reactive protein and interleukin-6 levels were high for patients receiving the drug. These data lead to the hypothesis that alternative mechanisms may be at work other that those linked to lipid changes and "classic" risk factors for atheroma. Consequently, we investigated the ultrasound characteristics of carotid plaques in HIV-positive patients comparing the results with those obtained from patients affected by atherosclerosis and patients with arteritis. The study population included 110 HIV-positive patients and 91 HIV-negative patients (61 atherosclerotic patients and 30 with arteritis). All patients were subjected to ultrasonography of the epi-aortic vessels. When compared to atherosclerotic patients, there was a significantly higher proportion of HIV-positive patients with hypoechogenic and homogeneous lesions, uniform in their parietal and endoluminal portions with a smooth or slightly irregular surface. No significant differences were found between HIV-positive and arteritis patients. This ultrasonographic study confirms that inflammatory mechanisms could play a major role in the onset of vascular damage in HIV-1 positive patients.

In modern factories, personal computers are starting to replace traditional programmable logic controllers, due to cost and flexibility reasons, and also because their operating systems now support programming environments even suitable for demanding real-time applications. These characteristics, as well as the ready availability of many software packages covering any kind of needs, have made the introduction of PC-based devices at the factory field level especially attractive. However, this approach has a profound influence on the extent of threats that a factory computing infrastructure shall be prepared to deal with. In fact, industrial personal computers share the same kinds of vulnerabilities with their office automation counterparts. Then, their introduction increases the risk of cyber-attacks. As the complexity of the network grows, the problem rapidly becomes hard to tackle by hand, due to the subtle and unforeseen interactions that may occur among apparently unrelated vulnerabilities, thus bearing the focus on the full automation of the analysis. Going into this direction, this paper presents a software tool that, given an accurate and machine-readable description of vulnerabilities, detects whether or not they are of concern and evaluates consequences in the context of a factory network.

Aim: To investigate the prevalence of tropical infections in immigrated patients hospitalized in 48 Italian operative units of infectious diseases during 2002. Patients and Methods: Each participating center was requested to fill a questionnaire regarding the type of discharge diagnosis, the country of origin, and demographic features (age, sex, resident status, and inscription in the National Health Service) of each hospitalized immigrant. Data were received from 48 Italian infectious disease clinics, with a total of 2255 immigrants hospitalized during 2002. Among this population, we have evaluated the prevalence of patients affected by imported tropical diseases. Results: Imported tropical diseases were found in 120 patients, representing 6% of the total of immigrated hospitalized patients. The prevalent disease was malaria (95 cases, 79.2%), followed by schistosomiasis (15 cases, 12.5%), amebiasis (8 cases, 6.6%), and dengue (2 cases, 1.6%). The patients affected by malaria (90 cases of infection by Plasmodium falciparum, 4 by Plasmodium vivax, and one by Plasmodium malaria) come principally from Africa (90%). Conclusions: The range of health problems in immigrants often became broad after their arrival in Italy and included infectious diseases, such as human immunodeficiency virus infection, tuberculosis, and viral hepatitis, which reflect their poor conditions in life.

To obtain data on the evolution of carotid lesions, we evaluated 133 patients at their first antiretroviral regimen, followed for at least 2 years; 77 treated with protease inhibitors (PIs): Group A and 56 with non-nucleosidic reverse transcriptase inhibitors (NNRTIs): Group B. All patients were subjected to carotid ultrasonography. In Group A, among the previously normal patients 22.5% developed lesions, 40% remained normal, 37.5% shifted to other antiretroviral regimens. Among the 37 previously pathologic patients, 46% worsened, 19% were stable, in 8% the lesions had disappeared, 27% shifted. In Group B, among the previously normal patients, 12.7% developed lesions, 80.8% remained unaltered, 6.5% shifted. Among the previously pathologic patients, 12.5% worsened, lesions reversed in 25%, remained stable in 50% and 12.5% shifted to PI. At statistical analysis, in Group A both the percentage of patients developing new lesions and the percentage of patients who worsened was significantly higher. In conclusion, we evidenced a more rapid onset of lesions in patients treated with PIs with respect to patients treated with NNRTIs and towards a more rapid evolution of the previous lesions. The shift from PIs to NNRTI/3 NRTI seems related to a lower rate of evolution. Interestingly, a disappearance of lesions was detected in both groups.

Grading programming assignments of courses on distributed programming can greatly benefit from extensive testing, especially if quality aspects such as portability, robustness, security, and performance have to be evaluated. This paper presents a framework that was developed at the Turin Polytechnic, Turin, Italy, to enable seamless and fast implementation of Web portals for automated management of student programming assignments. By using a computational grid facility to schedule testing jobs on different hosts, the framework offers high flexibility and scalability, thus enabling computationally intensive tests and some kinds of distributed tests, such as portability tests and field tests, which otherwise would be difficult to automate. The grid can be made of ordinary and even nondedicated or dismissed PCs, which, according to the authors' experience, is enough to offer students online extensive testing services. The framework was successfully used in two courses on distributed programming, located at different sites, partially overlapped in time, and attended by a total of 60 students. However, the framework should be scalable enough to work with increasing numbers of students and courses

People with severe mental disorders and a history of violence are often seen as a difficult-to-manage segment of the population. In addition, this group is usually characterized by a high risk of crime recidivism, and poor compliance with community and aftercare programs. To investigate a sample of male patients living in Residential Facilities (RFs) with a history of violent behavior against people and to compare their characteristics with those of never-violent residents; to analyze the associations between aggressive behaviors in the last two years and a history of previous violence; and, to assess the predictors of aggressive behaviors. This study is part of a prospective observational cohort study which involved 23 RFs in Northern Italy. A comprehensive set of sociodemographic, clinical, and treatment-related information was gathered, and standardized assessments were administered to each participant. Also a detailed assessment of aggressive behaviors in the past two years was carried out. The study involved 268 males: 81 violent and 187 never-violent. Compared to never-violent patients, violent patients were younger, with a higher proportion of personality disorders, and have displayed an increased number of aggressive behaviors in the last two years. The presence of a history of violent behavior in the past significantly increases the probability of committing aggressive acts in the future.

Objectives Nucleotide analogues may promote renal and bone toxicity. The aim of the present study was to evaluate markers of osteorenal toxicity in patients affected by hepatitis B virus-related chronic hepatitis treated with lamivudine plus adefovir who were switched to tenofovir. Patients and methods We evaluated 60 consecutive patients at the time of the switch of treatment and after 1, 3, 6, 9 and 12 months. The mean baseline estimated glomerular filtration rate (eGFR) was 89.3 ± 19.0 mL/min/1.73 m2. Results During the study period we observed a reduction in mean eGFR up to 6 months after switching to tenofovir, and this remained stable for the last two timepoints. At the end of study, the mean eGFR was 82.6 ± 21.5 mL/min/1.73 m2, a reduction of 7.5%. The mean baseline proteinuria was 202.6 ± 237.6 mg/24 h. Microhaematuria was observed in 22.6% of patients and hypophosphataemia in 18.6%. After 1 month of tenofovir, we observed a worsening of serum phosphate and parathyroid hormone levels, haemoglobinuria and 24 h proteinuria. After 3 and 12 months of tenofovir, these data tended to recover to baseline levels. A total of 92.6% of patients at baseline had hypovitaminosis D. After supplementation with cholecalciferol, this percentage decreased significantly. We observed a reduced bone mineral density (BMD) in 52.7% of patients at baseline; this increased to 77.8% after 6 months of tenofovir, but at the last timepoint the percentage of patients with a reduced BMD had fallen to a level above the baseline. Conclusions In conclusion, patients exposed to lamivudine plus adefovir showed relevant osteorenal damage. The switch to tenofovir provoked a slight reduction in eGFR that stabilized after 6 months. The reduced BMD at baseline did not worsen under tenofovir treatment.

The paper shows how secure telecommunication services supporting user and terminal mobility and service personalization can be designed using the SCARAB architecture, developed within the EU ACTS SCARAB project. The most important aspects of this architecture are the combined use of smart cards and mobile code technologies to solve the mobility and personalization issues, and the ability to support different types of terminals, ranging from powerful PC terminals to mobile personal digital assistants. These features are illustrated through the design of a demonstrative service.

Objectives: To evaluate the correlation between antiretroviral therapy (ART) and lesions of the carotid vessels using an ultrasound colour-Doppler technique. Design: A total of 293 HIV-1 infected patients underwent epiaortic vessel ultrasonogrdphy: 105 on treatment with protease inhibitors (PI) (group I), 125 PI-naive patients treated with a non-nucleoside reverse transcriptase inhibitor-including regimen (group II), and 63 patients treated with two nucleoside reverse transcriptase inhibitors or naive to ART (group III). Methods: Intima characteristics, pulsation and resistance indexes, and minimal, peak and mean speed were evaluated using a colour power doppler. Atherosclerotic plaques were described. Independent risk factors and values for glycaemia, cholesterolaemia and triglyceridaemia were considered. Statistical analysis included the Wilcoxon tests, the X 2 test, the Cochran Armitage trend test and the Mantel-Haenszel test and, when necessary, logistic regression analysis. Results: Of the 150 group I patients, 55 (52.4%) presented acquired lesions of the vascular wall at ultrasonography, whereas similar lesions were found in 19 out of 125 (15.2%) patients in group II and in nine of 63 (14.3%) in group III. ART, age, smoking and CD4 T-cell count were the main predictive risk factors for vascular lesions. However, the highest significance was with the use of PI. Conclusions: These data confirm the higher prevalence of premature carotid lesions in the PI-treated patients. A periodic ultrasonographic study of the vascular wall should be included in the follow-up of HIV infected patients.

Objective Enfuvirtide is the first of a new class of antiretroviral agents. The drug is safe and well tolerated; injection site reactions are the most common adverse events. The aim of this study was the clinical and histopathological evaluation of injection site reactions in patients treated for 80 weeks. Materials and methods Six patients were evaluated. Five of them underwent cutaneous biopsies using a 4 mm punch. Sections were stained with haematoxylin-eosin, periodic acid-Schiff stain and Verhoeff's stain. Moreover, immunohistochemical studies were carried out using CD20, CD45Ro and CD34 antibodies. Results Four different macroscopic patterns were presented: (a) no evidence of cutaneous lesions; (b) transient infiltrative lesions which auto-resolved within 24 h; (c) transient nodular lesions which auto-resolved within 7-15 days; and (d) stable lesions after more than 30 days with a scleroderma-like aspect. Histological examination showed three patterns: (1) an acute urticaria/vasculitis-like pattern with inflammation of the fat tissue; (2) a sub-acute pattern with an initial dermal sclerosis; (3) a chronic scleroderma-like pattern with connective tissue disposed around the adnexa, whose structure was intact. The immunohistochemical study evidenced a prevalence of T lymphocytes and a moderate neoangiogenesis. Conclusions In our experience, after a rather long period of treatment, cutaneous reactions comprised a variety of features largely independent of the virological and immunological outcome. The adnexa was unaltered in all patients, this indicating a tendency to a possible regression of the sclerotic lesions. Therefore, patients should be encouraged to rotate the sites of injection thus permitting the tissues to regenerate.

The purpose of this study was to compare the performance of a rapid immunochromatographic dipstick test for the qualitative detection of circulating antibodies to the leishmanial recombinant antigen K39 with that of a classical immunofluorescent antibody test for serodiagnosis of visceral leishmaniasis. Sera from 143 Italian subjects, including 69 patients with clinically suspected visceral leishmaniasis, 23 patients with hypergammaglobulinemia and 51 healthy controls, were tested. The immunochromatographic test was performed according to the manufacturer's instructions, using antigen-impregnated nitrocellulose paper strips. The immunofluorescent antibody test was performed according to an established method, using promastigotes of Leishmania infantum zymodeme Montpellier 1 as antigen. In 11 patients, diagnosis of active Leishmania infection was established by microscopic examination of biopsy samples and/or clinical response to meglumine antimoniate. Results of the two tests correlated for all but two sera examined. In two patients, one with proven infectious mononucleosis and one with bacterial pneumonia, the immunofluorescent antibody test was positive and the dipstick test was negative. In the restricted sample of patients in whom a definitive diagnosis was established, the immunochromatographic test was positive in 11 of 11 patients with confirmed Leishmania infection and negative in 103 of 103 subjects who either had other documented diseases or were healthy controls, showing 100% sensitivity and 100% specificity.

Introduction PREVALEAT II (PREmature VAscular LEsions and Antiretroviral Therapy II) is an ongoing multicenter, longitudinal cohort study aimed to the evaluation of cardiovascular (CV) risk in advanced HIV-infected antiretroviral (ARV) naïve patients starting their first antiretroviral therapy (ART). Patients and methods All consecutive naïve patients with CD4 cell count 200. Conclusions Our data evidence at baseline has a relevant deterioration of CV conditions in terms of ultrasonographic data, FMD, inflammation and cytokine markers among advanced naïves. During follow-up epi-aortic lesions tend to worsen but not significantly, percentage of pathologic FMD remains stable. Regarding markers of endothelial activation ICAM-1 significantly worsens during the period of observation; also VCAM-1 has a trend towards the worsening while not significantly. Conversely, a significant improvement was observed for the markers of inflammation D-dimers and high sensitivity C-reactive protein (hsCRP). IL-6 improved but not significantly. Serum lipid profile shows an increase of HDLc and total cholesterol, but not of LDLc. In conclusion, after a twelve-month follow-up period, CV risk of the patients remains high. ARV therapy seems in fact to improve only non-specific and poor sensitive inflammation biomarkers and HDLc; markers of endothelial activations tend to worsen, intima-media ultrasonography and FMD do not show relevant modifications. Further data are warranted to better understand the role of the different ARV regimens.