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Evidences on the absence of risk of sexual transmission of HIV by persons living with HIV/AIDS (PLWHA) with undetectable plasma HIV-RNA (HIV-RNA200 copies/ml) led to the worldwide campaign "U = U" (undetectable = untransmittable). The purpose of this study was to evaluate the perceived accuracy of this message among PLWHA, HIV-negative people having unprotected sex (PHUS) and infectious diseases' (ID) physicians in Italy. A nationwide survey has been conducted using three different anonymous questionnaires (for ID physicians, PLWHA and PHUS). A total of 1121 participants filled the questionnaires: 397 PLWHA; 90 physicians; 634 PHUS. Awareness of U = U message has been reported in 74%, 92% and 47% of PLWHA, ID physicians and PHUS, respectively. The perception of accuracy of the U = U message among those aware was reported as high in 80.4%, 79.5% and 67.3% of PLWHA, ID physicians and PHUS, respectively. Physicians perceived that 11% of PLWHA have a high rate of perception of U = U, whereas among PLWHA, only 34% reported definitive positive messages from physicians. Discrepancies between awareness and perception of accuracy of the message U = U in PLWHA and physicians have been found, suggesting still low confidence in the community regarding the message itself.

ObjectivesTo assess the effectiveness of tecovirimat (TPOXX) for treating mpox in terms of difference in healing time and extent of viral clearance.DesignEmulation of a target trial based on observational data.SettingItalyParticipantsForty-one men hospitalized for mpox as of September 29th, 2022.Main outcome measuresMain outcome was the time to clinical recovery. Secondary outcome was the variation in viral load in the upper respiratory tract (URT) after treatment.ResultsThe median time from symptoms onset to hospital admission and to initiation of TPOXX was 4 days (IQR 2-6) and 10 days (IQR 8-11), respectively. Fifteen patients completed a course of therapy. No deaths were observed; the overall median healing time was 21 days (IQR 17-26). We found no evidence for a significant improvement in recovery time in treated vs. untreated patients, with an estimated mean of 14.7 days for both groups. A subset of 13 patients had URT samples at T1 (median of 5 days (IQR 3-7) from symptoms onset) and T2 (median 7 days (IQR 7-9) from T1). Overall, mean viral load was 4.65 (0.30) vs. 4.91 (0.35) (log2 scale of cycle threshold) at T1 and T2, respectively. In the unadjusted analysis, variation over T1-T2 was lower in the treated 0.13 log2 (SD=0.53) vs. untreated 0.37 (0.50), although not statistically significant (unpaired t-test p=0.41). After controlling for confounding, there was no evidence for a difference in the potential changes over T1-T2 by treatment arm, and our estimate of the average treatment effect (ATE) was consistent with no difference by treatment group, although with large 95% CI around these estimates.ConclusionsOur analysis seems to exclude a clinically important effect of TPOXX in hospitalized mpox patients when compared to no treatment. These data are one of the valuable currently available sources of evidence to guide treatment decisions in patients hospitalized with TPOXX. Pending more robust data from randomized comparisons, the use of TPOXX should be restricted to the clinical trials setting.Trial registration“MpoxCohort” observational study protocol: approval number 40z, Register of Non-Covid Trials 2022.

Background WHO defines Post–Acute Sequelae of SARS–CoV–2 (PASC) as a condition that occurs several weeks after the infection, which persists for at least 8 weeks and cannot be explained by alternative diagnoses. Symptoms of PASC are: palpitations, dyspnoea, chest pain. These symptoms require an initial cardiological investigation, but also a cardiological follow–up that could be carried out with telemedicine. Principal aim: To assess the feasibility of cardiological televisit and its socio–economic impact in patients with PASC. Secondary aims: 1) To describe the clinical, laboratory and instrumental characteristics of patients with PASC and to define the possible role of cardiovascular risk factors in the development of the disease; 2) To correlate the symptoms reported by the patients with any clinical objectivity or instrumental alterations; 3) To assess the patient‘s perception of the use of specialist televisit and its possible economic and social impact. Methods Prospective observational study. All patients with previous COVID–19 with suspected PASC will be screened. After the first cardiological face–to–face visit, patients with suspected PASC who require follow–up will be consecutively enrolled and assigned in a 1:1 ratio to the televised study group (GT) and the standard of care (GC) control group. Patients in the GT group will perform the control cardiology examination in televisit, while patients in the GC group will perform the cardiological control according to the current standard of care. The specialist televisit (booking mode, use of freeware platform) will be provided as indicated by the latest regional directives. Exclusion criteria: Failure to sign informed consent; inadequate computer literacy (of the patient or his/her caregiver). Evaluation: Patients in the GT and GC group will take a questionnaire with specific questions on how the specialist check–up will be delivered. Expected results: The use of televisit for the follow–up of patients with PASC, as defined in this protocol, play a key role for the digital transition in our operational context and, above all, for the optimisation of healthcare resources.

BackgroundOmicron variant questioned the efficacy of the approved therapies for the early COVID-19. I In vitro data show retained neutralizing activity against BA.1 and BA.2 for remdesivir (RDV), molnupiravir (MLN), and nirmatrelvir/ritonavir (NRM/r), while poor efficacy for Sotrovimab (STR) against BA.2. No data about the risk of clinical failure and in vivo antiviral activity are available.Material and methodsSingle-center observational comparison study enrolling all consecutive patients with a confirmed SARS-CoV-2 Omicron (BA.1 or BA.2) diagnosis and who met eligibility criteria for treatment with RDV, MLN, NRM/r, or STR. Treatment allocation was subject to drug availability, time from symptoms onset, and comorbidities. Patients were followed through day 30. Nasopharyngeal swab (NPS) VL was measured on day 1 (D1) and D7 and was expressed by log2 cycle threshold (CT) scale. Comparisons between groups were made by Chi-square and Wilcoxon paired-test. Primary endpoint was D1-D7 VL variation. Potential decrease in VL and average treatment effect (ATE) were calculated from fitting marginal linear regression models weighted for calendar month of infusion, duration of symptoms, and immunodeficiency. Secondary endpoints were the proportion of D7 undetectable VL in NPS and clinical outcomes compared by treatment groups using a Chi-square test.ResultsA total of 521 pts received treatments (STR 202, MLN 117, NRM/r 84, and RDV 118): female 250 (48%), median age 66 yrs (IQR 55-76), 90% vaccinated; 15% with negative baseline serology. At D1, median time from symptoms onset was 3 days (2,4). 378 (73%) pts were infected with BA.1 and 143 (27%) with BA.2. D1 mean viral load was 4.12 log2 (4.16 for BA.1 and 4.01 for BA.2). The adjusted analysis showed that NRM/r significantly reduced VL compared to all the other drugs in pts infected with BA.1 while no evidence for a difference vs. MLP was seen in those infected with BA.2. MLN had comparable activity to STR against BA.1 and to NRM/r against BA.2. There was no significant difference between STR and RDV for BA.2.At D7, 35/521 (6.7%) pts had undetectable VL. Of these, 31 were infected with BA.1 [9 (9%) MLN, 7 (14%) NRM/r, 7 (8%) RDV, and 8 (5%) STR)], and only 4 with BA.2, all treated with NRM/r. After 30 days of follow-up, 9/568 pts experienced COVID-19-related clinical failure [7/226 STR (5 BA.1) and 2/87 NRM /r (2 BA.1)].ConclusionsIn this analysis of in vivo early VL reductions, NRM/r appears to be the drug showing the greatest antiviral activity regardless of the VoC, together with MLN, although the latter limited to people with BA.2. In the Omicron era, due to the high prevalence of vaccinated people and the lower probability of hospital admission, VL decrease can be a valuable surrogate of drug activity.

Background Due to the total lockdown during COVID–19 pandemic, clinicians were forced to organize telephone visits or tele–monitoring. We developed a standardized multiparametric questionnaire, suitable for telephone administration to older heart failure (HF) patients and/or their caregivers. Purpose To compare clinical characteristics of the three groups (green, yellow, red) of patients classified by baseline TeleHFCovid19–Score and evaluate its ability to predict one–month in elderly patients with chronic HF. Methods The TeleHFCovid–19 score was obtained from a multiparametric questionnaire administered, from April 2020, during televisits to patients (or caregivers), which were divided in progressively increasing risk groups: green (0–3), yellow (4–8) and red (≥9). The primary study outcome was a composite of death from cardiovascular causes and/or hospitalization for HF, which individually were secondary outcomes. Results We enrolled 146 patients. Mean age was 81±9 years, females were 40%. In all the study population there was a high prevalence of self–reported adherence to guidelines–recommended drug treatments and behavioural measures, as well as a broad intake of diuretic therapy. Patients in green group had lower use of high dose loop diuretic (p Conclusions The TeleHFCovid19–Score score was able to correctly recognize a low risk, green group. Therefore, the score could be used to identify low risk patients which could be followed remotely, reserving a tighter on–site clinical follow–up to higher events risk patients.

Background A multidisciplinary heart team and continuum care approach seems to be the most appropriate clinical strategy in order to reduce mortality, functional decline and disability of frail and clinical complex oldest old patients affected by heart failure (HF). We analysed the independent predictors of 1 year–total mortality in our cohort of oldest old HF patients. Methods All patients aged > 85 years referred to our Heart Failure Unit of a Tertiary teaching hospital were consecutively enrolled in the study and were evaluated at first visit with a comprehensive assessment recording cardiological, geriatric and bio–humoral variables. Then we assessed with a multivariable Cox regression analysis the independent predictors of 1–year all–cause mortality. Results 87 patients were enrolled (mean age 89 ± 2.7 years, range 86–96 years); 48.9% were females, 57.9% were in NYHA class III or IV, 43.2% had HFpEF, 36.4% had an ischemic aethiology, 69.3% had a history of atrial fibrillation, 19.3% were living alone, the mean number of prescribed drugs was 8.8 ± 2.2, EVEREST congestion score was 5.2 ± 2.6, mean NT–proBNP was 8187 ± 11170 pg/ml. In the year after enrolment, 25 patients (34.1%) had more than one HF hospitalisation and 17 patients (19%) died. Among all clinical variables, living alone, having had one or more HF hospitalisation and HF–type (HFpEF, HFmrEF, HFrEF), EVEREST congestion score, trans–tricuspid gradient and tricuspid annular plane systolic excursion were significantly (p Conclusions In a cohort of HF oldest old patients tightly managed in a dedicated cardiologic and geriatric Heart Failure Unit, 1–year all–cause mortality was independently predicted by a clinical score of congestion and by living alone status.

Introduction Chronic pain assessment and post-treatment evaluation continues to be challenging due to a lack of validated, objective tools to measure patient outcomes. Validation of mechanistic pain biomarkers would allow clinicians to objectively identify abnormal biochemistry contributing to painful symptoms. Methods We describe the clinical validation of a multi-biomarker assay with algorithmic analysis known as the Foundation Pain Index (FPI) in diverse cohorts of chronic pain patients in a prospective, cross-sectional, observational validation study. Levels of 11 urinary pain biomarkers were measured and tabulated using a proprietary algorithm to generate FPI scores for chronic pain subjects (N = 153) and age- and sex-matched pain-free controls (N = 334). Results FPI scores were significantly correlated with the 36-Item Short Form Health Survey (SF-36) scores among chronic pain subjects (P value

The new variant Omicron (B.1.1.529) of SARS-CoV-2, first identified in November 2021, is rapidly spreading all around the world. The Omicron becomes the dominant variant of SARS-CoV-2. There are many ongoing studies evaluating the effectiveness of existing vaccines. Studies on neutralizing activity of vaccinated sera against Omicron variant are currently being carried out in many laboratories.In this study, we have shown the neutralizing activity of sera against SARS-CoV-2 Omicron (B.1.1.529) variant compared to the reference Wuhan D614G (B.1) variant in individuals vaccinated with 2 doses of Sputnik V or BNT162b2 in different time points up to 6 months after vaccination. We performed analysis on sample pools with comparable NtAb to Wuhan D614G variant. The decrease in neutralizing antibody (NtAb) to the Omicron variant was 8.1 folds for group of Sputnik V-vaccinated and 21.4 folds for group of BNT162b2-vaccinated. Analysis showed that 74.2% of Sputnik V- and 56.9% of BNT162b2-vaccinated sera had detectable NtAb to SARS-CoV-2 Omicron variant.The decrease in NtAb to SARS-CoV-2 Omicron variant compared to Wuhan variant has been shown for many COVID-19 vaccines in use, with some showing no neutralization at all. Today the necessity of third booster vaccination is obvious. And the most effective approach, already shown in several studies, is the use of heterologous booster vaccination pioneered in COVID-19 vaccines by Sputnik V.

The objective of this study is to identify a simplified rapid screening and linkage-to-care model for HCV among PWUD.The study stems from a collaborative project bringing together two local Italian Centers for Drug Addiction and the Hepatology-Infectious Diseases Department of Lazzaro Spallanzani. A research physician analyzed the available medical records seeking to identify HCV and HIV infected patients in care in the addiction centers. Between March 2018 and January 2020 subjects were selected from among a cohort of 720 PWUD in the two Centers' care. The study comprises three steps: first, screening for HCVAb; second, the linkage to care; third, clinical assessment to treatment. The research physician recruited patients for the first two steps directly in their local addiction center. The third step was conducted in the Spallanzani. The characteristics of those subjects who adhered to the three-step study program were then compared to those of the non-adhering PWUD.194 were known HCVAb positive patients. Of the 505 PWUD in the care of the two Centers eligible for screening, 364 were enrolled in the study. 144 resulted HCVAb positive. 269 were tested for HCVRNA. 101 underwent a full assessment. 96 patients started antiviral therapy with DAA. Patients who refused first step screening were older patients and mainly heroin users; in the second step, almost all the HIV/HCV co-infected patients agreed to a viremia test; in the third step all the HIV/HCV co-infected patients refused HCV treatment.The study suggests an on-site specialist approach conducted directly in the addiction centers themselves starting from screening; it can bring the goal of HCV PWUD microelimination closer.

Purpose Multidrug-resistant tuberculosis (MDR-TB) is a major burden to public health in low incidence countries in Europe. The aim of this study was to attempt to have a better insight into the trends of MDR-TB in the metropolitan area of Rome, within the Italian and the foreign-born population, based on microbiological and demographic data. Patients and methods We performed a prospective study, collecting microbiological data based on phenotypic drug-resistant testing (DST) of TB strains consecutively isolated in a referral hospital in Rome, the capital city of a low TB incidence country, over a 6-year period, and correlated them to the geographical origin of patients. This study was carried out in a referral hospital for patients with drug-resistant TB from the whole region. Results Drug-resistance data from 926 patients with a microbiological diagnosis of TB from 2011 to 2016 show a 5.5% rate of MDR-TB, mostly occurring in patients born in a single East European country, that has a high incidence of MDR-TB. The strains isolated from these patients frequently carry additional resistances, leading to an increased risk of developing extensively drug-resistant (XDR) TB. Conclusion In the great metropolitan area of Rome, MDR-TB more frequently occurs in patients who were born in a single country from Eastern Europe known to have high rates of MDR-TB and long-time residents in Italy. Recent immigrants from non-European countries do not appear to contribute to the rates of MDR-TB reported in this article. This knowledge of local TB trends could help improve the measures of surveillance and prevention of disease.

ObjectivesOur aim was to investigate the durability of different initial regimens in patients starting ART with CD4+ counts 5 log10 copies/mL.MethodsThis was a retrospective study of HIV-infected patients prospectively followed in the ICONA cohort. Those who started ART with boosted protease inhibitors (bPIs), NNRTIs or integrase strand transfer inhibitors (InSTIs), with CD4+ 5 log10 copies/mL, were included. The primary endpoint was treatment failure (TF), a composite endpoint defined as virological failure (VF, first of two consecutive HIV-RNA >50 copies/mL after 6 months of treatment), discontinuation of class of the anchor drug or death. Independent associations were investigated by Poisson regression analysis in a model including age, gender, mode of HIV transmission, CDC stage, HCV and HBV co-infection, pre-treatment HIV-RNA, CD4+ count and CD4+/CD8+ ratio, ongoing opportunistic disease, fibrosis FIB-4 index, estimated glomerular filtration rate, haemoglobin, platelets, neutrophils, calendar year of ART initiation, anchor drug class (treatment group) and nucleos(t)ide backbone.ResultsA total of 1195 patients fulfilled the inclusion criteria: 696 started ART with a bPI, 315 with an InSTI and 184 with an NNRTI. During 2759 person-years of follow up, 642 patients experienced TF. Starting ART with bPIs [adjusted incidence rate ratio (aIRR) (95% CI) 1.62 (1.29–2.03) versus starting with NNRTIs; P ConclusionsIn patients starting ART with 5 log10 HIV-RNA copies/mL, the durability of regimens based on InSTIs was longer than that of NNRTI- and bPI-based regimens.

Item does not contain fulltext BACKGROUND: The sympathetic nervous system (SNS) is important in the regulation of perfusion. Dorsal root ganglion stimulation (DRG-S) modulates sympathetic tone and is approved to treat complex regional pain syndrome, a disorder related to SNS dysfunction. We herein present 3 cases of DRG-S therapy to improve blood flow and symptoms of ischemia in peripheral arterial disease (PAD). METHODS: Patient 1 is a 44-year-old female with dry gangrene of the third and fourth digits of her right hand due to Raynaud's syndrome who was scheduled for amputation of the affected digits. DRG-S leads were placed at the right C6, 7, and 8 DRG. Pulse volume recordings (PVR) were measured at baseline and after DRG-S. Patient 2 is a 55-year-old female with a non-healing ulcer of her left foot secondary to PAD scheduled for a below the knee amputation who underwent a DRG-S trial with leads placed at the left L4 and L5 DRG followed by a spinal cord stimulation trial with leads placed at the T9-T10 spinal levels for comparison. Transcutaneous oximetry (TcPO2) was measured at baseline and after 3 days of each therapy. Patient 3 is a 69-year-old female with persistent left foot pain at rest secondary to PAD with DRG-S leads placed at the left L4 and S1 levels. RESULTS: All 3 patients experienced a significant reduction in pain with DRG-S, along with improvements in blood flow of the involved extremities, avoiding or limiting amputation. PVR improved dramatically with DRG-S in patient 1. A greater improvement in TcPO2 was seen with the DRG-S trial compared to spinal cord stimulation trial in patient 2. Patient 3 experienced an increase in walking distance and demonstrated long term efficacy and limb salvage at 32 months postimplantation. CONCLUSIONS: Modulation of SNS output from DRG-S through orthodromic and antidromic autonomic pathways is likely responsible for improving blood flow. DRG-S may be a treatment option for PAD.

BACKGROUND: Using 2004–2007 TB:HIV Study data from Europe and Latin America, we previously generated a health care index (HCI) for TB and HIV co-infected people. With improvements in diagnostic and management practices, we have now updated the HCI with new data.METHODS: We evaluated nine aspects of health care in Cox proportional hazards models on time from TB diagnosis to death. Kaplan-Meier methods were used to estimate the probability of death by HCI quartile.RESULTS: Of 1396 eligible individuals (72% male, 59% from Eastern Europe), 269 died within 12 months. Use of rifamycin/isoniazid/pyrazinamide-based treatment (HR 0.67, 95% CI 0.50–0.89), TB drug susceptibility testing (DST) and number of active TB drugs (DST + . Lower HCI was associated with an increased probability of death; 30% (95% CI 26–35) vs. 9% (95% CI 6–13) in the lowest vs. the highest quartile.CONCLUSION: We found five potentially modifiable health care components that were associated with mortality among TB-HIV positive individuals. Validation of our HCI in other TB cohorts could enhance our findings.

Purpose Multidrug-resistant tuberculosis (MDR-TB) is a major burden to public health in low incidence countries in Europe. The aim of this study was to attempt to have a better insight into the trends of MDR-TB in the metropolitan area of Rome, within the Italian and the foreign-born population, based on microbiological and demographic data. Patients and methods We performed a prospective study, collecting microbiological data based on phenotypic drug-resistant testing (DST) of TB strains consecutively isolated in a referral hospital in Rome, the capital city of a low TB incidence country, over a 6-year period, and correlated them to the geographical origin of patients. This study was carried out in a referral hospital for patients with drug-resistant TB from the whole region. Results Drug-resistance data from 926 patients with a microbiological diagnosis of TB from 2011 to 2016 show a 5.5% rate of MDR-TB, mostly occurring in patients born in a single East European country, that has a high incidence of MDR-TB. The strains isolated from these patients frequently carry additional resistances, leading to an increased risk of developing extensively drug-resistant (XDR) TB. Conclusion In the great metropolitan area of Rome, MDR-TB more frequently occurs in patients who were born in a single country from Eastern Europe known to have high rates of MDR-TB and long-time residents in Italy. Recent immigrants from non-European countries do not appear to contribute to the rates of MDR-TB reported in this article. This knowledge of local TB trends could help improve the measures of surveillance and prevention of disease.

Background: We evaluate differences in timing of cART (combined antiretroviral treatment) initiation by geographical origin in male and female HIV-positive patients in the Collaboration of Observational HIV Epidemiological Research Europe, a large European Collaboration of HIV Cohorts. Methods: We included individuals recruited in Western Europe between January 1997 and March 2013, with known geographical origin and at least 1 CD4(+) cell countmeasurement while cART-naive. Timing of cART was assessed through modified time-to-eventmethods, in which a scale of CD4(+) cell counts was used instead of time, with cART being the outcome. We estimated the median CD4(+) cell count at cART initiation (estimated CD4(+) levels at which the probability of having started cART is 50%) using Kaplan-Meier and adjusted hazard ratios of cART initiation using Cox regression. Results: Of 151 674 individuals, 110 592 (72.9%) were men. Median (95% confidence interval) CD4(+) cell count falls far below 250 cells/ml in all groups and was lowest in sub-Saharan African [SSA: 161 (158-167)], Caribbean men [161 (150-174)] and in Asian women [Asian Continent and Oceania: 185 (165-197)]. Among men, the adjusted probability of cART initiation was lower in migrants compared with natives, but differences depended on initial CD4(+) cell count. For example, in the group with more than 500 CD4(+) at recruitment, they were 45% (36-53%), 30% (17-40%) and 25% (19-30%) lower for Caribbean, Eastern European and SSA men, respectively. In women, no meaningful differences were observed between natives and most migrant groups. However, SSA women had a 31% (24-38%) higher probability of cART initiation when recruited at a CD4(+) more than 500 cells/ml and 9% (4-14%) lower when recruited at CD4(+) less than 100 cells/ml. Conclusion: Most migrant men initiate cART at lower CD4(+) cell count than natives, whereas this does not hold for migrant women.

Summary Objectives Mortality among HIV patients with tuberculosis (TB) remains high in Eastern Europe (EE), but details of TB and HIV management remain scarce. Methods In this prospective study, we describe the TB treatment regimens of patients with multi-drug resistant (MDR) TB and use of antiretroviral therapy (ART). Results A total of 105 HIV-positive patients had MDR-TB (including 33 with extensive drug resistance) and 130 pan-susceptible TB. Adequate initial TB treatment was provided for 8% of patients with MDR-TB compared with 80% of those with pan-susceptible TB. By twelve months, an estimated 57.3% (95%CI 41.5–74.1) of MDR-TB patients had started adequate treatment. While 67% received ART, HIV-RNA suppression was demonstrated in only 23%. Conclusions Our results show that internationally recommended MDR-TB treatment regimens were infrequently used and that ART use and viral suppression was well below the target of 90%, reflecting the challenging patient population and the environment in which health care is provided. Urgent improvement of management of patients with TB/HIV in EE, in particular for those with MDR-TB, is needed and includes widespread access to rapid TB diagnostics, better access to and use of second-line TB drugs, timely ART initiation with viral load monitoring, and integration of TB/HIV care.

Objective The Epiducer lead delivery system is a novel lead delivery device that can be used to percutaneously implant S-Series paddle leads (St. Jude Medical, Plano, TX, USA) as well as multiple percutaneous leads obviating the need for laminectomy and/or multiple needle sticks, respectively. This study evaluates the safety and usage of the Epiducer lead delivery system. Methods An Institutional Review Board-approved observational data collection study was conducted to evaluate usage patterns of the Epiducer system. In addition to the number and frequency of different lead configurations, the following procedural aspects of the surgery were recorded during the evaluation: angle of entry, distance from entry to final lead placement, and physician feedback. Descriptive statistics on adverse events, procedural aspects, and patient outcomes were compiled. Results Data were collected from 163 patients across 25 investigational sites. Physicians successfully implanted patients using the Epiducer during 89% of the procedures. Seven possible lead configurations were implanted. There were 96% and 92% of physicians “satisfied” or “very satisfied” with accessing the epidural space and placing multiple leads with the Epiducer delivery system, respectfully. Eighty-nine percent of physicians were “satisfied” or “very satisfied” with implanting an S-Series paddle lead using the Epiducer delivery system. Ninety-five percent of physicians were “satisfied” or “very satisfied” with the Epiducer delivery system overall. Ten patients (6%) experienced adverse events. Conclusion Results suggest that the Epiducer delivery system allows for the safe and successful percutaneous implantation of paddle leads and/or multiple lead configurations. Furthermore, physicians are satisfied with the Epiducer delivery system.

Combination antiretroviral therapy (cART) has become the main driver of total costs of caring for persons living with HIV (PLHIV). The present study estimated the short/medium-term cost trends in response to the recent evolution of national guidelines and regional therapeutic protocols for cART in Italy.We developed a deterministic mathematical model that was calibrated using epidemic data for Lazio, a region located in central Italy with about six million inhabitants.In the Base Case Scenario, the estimated number of PLHIV in the Lazio region increased over the period 2012-2016 from 14 414 to 17 179. Over the same period, the average projected annual cost for treating the HIV-infected population was €147.0 million. An earlier cART initiation resulted in a rise of 2.3% in the average estimated annual cost, whereas an increase from 27% to 50% in the proportion of naïve subjects starting cART with a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen resulted in a reduction of 0.3%. Simplification strategies based on NNRTIs co-formulated in a single tablet regimen and protease inhibitor/ritonavir-boosted monotherapy produced an overall reduction in average annual costs of 1.5%. A further average saving of 3.3% resulted from the introduction of generic antiretroviral drugs.In the medium term, cost saving interventions could finance the increase in costs resulting from the inertial growth in the number of patients requiring treatment and from the earlier treatment initiation recommended in recent guidelines.

The ontogeny of the γ-aminobutyric acid (GABA)-positive neurons in the brain of Xenopus laevis tadpoles was investigated by means of immunohistochemistry, using specific antibodies both against GABA and its biosynthetic enzyme, glutamate decarboxylase (GAD). The results obtained with the two antisera were comparable. The GABA system differentiates very early during development. At stages 35/36, numerous GABA-positive neurons were seen throughout the prosencephalon and formed two main bilateral clusters within the lateral walls of the forebrain that ran caudally toward the hindbrain. Other GABA-immunolabeled cell bodies, together with a conspicuous network of GABAergic fibers, were seen in the posterior hypothalamus. In the spinal cord, the lateral marginal zone was GABA-positive, as were Rohon-Beard neurons, interneurons, and Kolmer-Agdhur cells. A very rich GABA innervation was observed in the pars intermedia of the pituitary. At stage 50, plentiful immunopositive neurons and fibers were found in the telencephalic hemispheres, the diencephalon, and the mesencephalon (optic tectum and tegmentum). By stage 54, the number of GABA-immunoreactive neurons in the posterior hypothalamus had decreased, so that, at stage 58, there were very few GABA-labeled cell bodies in the dorsolateral walls of the infundibulum, despite a strong GABAergic innervation within the median eminence and the pars intermedia. From stage 58 to stage 66, the distribution pattern was very similar to that described in the adult X. laevis and in other amphibian species. These results point to transient GABA expression within the hypothalamus, possibly related to either 1) a naturally occurring cell death or 2) a phenotypic switch. © 1996 Wiley-Liss, Inc.

Introduction : Criteria of cART initiation after a first ADE have been modified over time based on evidence suggesting that treatment should be initiated earlier. The impact of these changes on clinical practice is unknown. Objective of this analysis was to evaluate temporal changes of time of starting cART after a first diagnosis of ADE in ART-naive patients (pts). Methods : All HIV+ enrolled in ICONA Foundation Study who presented with a diagnosis of ADE while cART-naive regardless of CD4 cell count were included. Pts were grouped according to have ADE for which additional medications that may have interactions with cART are required (Tb, atypical mycobacteriosis, non-Hodgkin lymphoma) [group A], ADE treatable only by cART (PML, isosporidiasis/cryptosporidiasis, KS, wasting syndrome) [group B] and ADE treatable with specific drugs (PCP, toxoplasmic encephalitis, CMV disease, esoph candidiasis, bacterial pneumonia, cervical cancer, cryptococcosis) [group C]. Standard survival analysis by KM was used to estimate the cumulative percentage of pts starting cART, overall and after stratification for calendar period of diagnosis (1996-2000, 2001-2008, 2009-2011) and type of ADE (groups A, B, C). Multivariable Cox regression was used to investigate association between calendar year of ADE and time to cART initiation after controlling for demographics. Summary of results : A total of 715 pts with a first ADE were observed over 1996-2011 (group A, n=187; B, n=123; C, n=405). 519 (73%) male, median age 38 (IQR:33-45), median CD4+ 64 (23-187)/mm 3 and HIV/RNA 5.25 (4.57-5.70) log 10 cps/mL, with no differences by calendar period. By 30 days from ADE, 23% (95% CI: 19-27) of those diagnosed in 1996-2000 have started cART vs. 32% (95% CI: 25-39) in 2001-2008 and 36% (28-44) after 2009 (log-rank p=0.001). After stratifying by CD4 at ADE, 45% of pts with CD4 201/mm 3 had started cART by 30 days (p

Dry-phase oxidation of two subbituminous coals and a lignite was carried out in a fluidized bed reactor at 200 °C, at different oxygen partial pressures and reaction times up to 4 h. The formation and evolution of various oxygenated functional groups (ester, carboxyl, ketone and hydroxyl) was investigated by FT-i.r. spectroscopy using a curve-resolving procedure and acetylation of coal samples. The development of alkali solubility of the coal as a function of reaction time was studied and the average molecular weight of regenerated humic acids (RHA) extracted from the oxidized coal was determined. The lower molecular weight of RHA extracted from highly oxidized coal samples suggests that besides the build-up of various oxygenated functional groups, the development of alkali solubility also results from concomitant ‘depolymerization’ of the coal network. The latter may occur through oxidation of aliphatic cross-links and formation of ester groups hydrolysable in basic solution. The FT-i.r. results were correlated with the development of alkali solubility. Some oxidation pathways are proposed.

Across Europe, almost a third of individuals infected with HIV do not enter health care until late in the course of their infection. Surveillance to identify the extent to which late presentation occurs remains inadequate across Europe and is further complicated by the lack of a common clinical definition of late presentation. The objective of this article is to present a consensus definition of late presentation of HIV infection.Over the past year, two initiatives have moved towards a harmonized definition. In spring 2009, they joined efforts to identify a common definition of what is meant by a 'late-presenting' patient.Two definitions were agreed upon, as follows. Late presentation: persons presenting for care with a CD4 count below 350 cells/μL or presenting with an AIDS-defining event, regardless of the CD4 cell count. Presentation with advanced HIV disease: persons presenting for care with a CD4 count below 200 cells/μL or presenting with an AIDS-defining event, regardless of the CD4 cell count.The European Late Presenter Consensus working group believe it would be beneficial if all national health agencies, institutions, and researchers were able to implement this definition (either on its own or alongside their own preferred definition) when reporting surveillance or research data relating to late presentation of HIV infection.

Background: : Individuals with advanced HIV infection naïve to antiretroviral therapy represent a special population of patients frequently encountered in clinical practice. They are at high risk of disease progression and death, and their viroimmunologic response following the initiation of highly active antiretroviral therapy may be more incomplete or slower than that of other patients. Infection management in such patients can also be complicated by underlying conditions, comorbidities, and the need for concomitant medications. Aim: : To provide practical guidelines to those clinicians providing care to HIV-infected patients in terms of diagnostic assessment, monitoring, and treatment. Conclusions: : The principals of antiretroviral treatment in asymptomatic naïve patients with advanced HIV infection are the same as those applicable to the general population with asymptomatic HIV infection. Naïve patients with advanced HIV infection and a history of AIDS-defining illnesses urgently need antiretroviral treatment, with the choice of antiretroviral regimen and timetable based on such factors as concomitant treatment and prophylaxis, drug interactions, and potential concomitant drug toxicity. Finally, an adequate counseling program - both before and after HIV-testing - that includes aspects other than treatment adherence monitoring is a crucial step in disease management. © 2009 Springer.

The objective of this study was to examine the effectiveness of using synthesis gas and water as reacting atmosphere for the catalytic conversion of coal/oil mixtures (coprocessing) to distillable material. Results of this work show that the presence of conventional supported hydrogenation catalysts can promote direct hydrogenation reactions as well as in situ hydrogen generation via water-gas shift reaction thus enhancing the process performances. The quality of the conversion products was not modified by changing the reacting gas from hydrogen to synthesis gas.

The prevalence of HIV/AIDS among people in midlife and late adulthood has been increasing in Western countries over the last decade. We analyzed data from a prospective, observational multi-centre study on individuals newly diagnosed with HIV between January 2004 and March 2007 in 10 public counselling and testing sites in Latium, Italy. At diagnosis, routine demographic, epidemiological, clinical and laboratory data are recorded, and patients are asked to complete a questionnaire investigating socio-demographic and psycho-behavioural aspects. To analyze the association of individual characteristics with age, we compared older adults (> or = 50 years) with their younger counterpart (18-49 years). To adjust for potential confounding effect of the epidemiological, clinical and behavioural characteristics, to identify factors associated with older age at HIV diagnosis, multivariate logistic regression analysis was performed. Overall, 1073 individuals were identified, 125 of whom (11.6%) were aged 50 years or above. The questionnaire was completed by 41% (440/1073). Compared with their younger counterparts, a higher proportion of older patients were males, born in Italy, reported heterosexual or unknown HIV risk exposure, were never tested for HIV before and were in a more advanced stage of HIV infection at diagnosis. In addition, older adults had a lower educational level and were more frequently living with their partners or children. With respect to psycho-behavioural characteristics, older patients were more likely to have paid money for sex and have never used recreational drugs. Interestingly, no differences were found regarding condom use, which was poor in both age groups. These findings may have important implications for the management of older adults with HIV, who should be targeted by appropriate public health actions, such as opportunistic screening and easier access to healthcare. Moreover, strategies including information on HIV and prevention of risk behaviours are needed.

Cellular immunity has a pivotal role in the pathogenesis of chronic pancreatitis (CP), resulting in pancreas infiltration by T-cells. Studies on systemic immunity are few and contradictory. One study reported a decrease of naive CD45RA+ cells. The presence of naive T cells, detected as recent thymic emigrants (RTEs), is evaluated with a new molecular technique by using real-time PCR to detect the T-cell receptor excision circles (TREC). To elucidate the role of naive T-cells in the pathogenesis of CP, we investigated the percentage of sj-TREC in CP patients.Thirty CP patients were studied and compared to 30 sex- and age-matched healthy volunteers.Genomic DNA was isolated from peripheral blood mononuclear cells (PBMC) of each patient. RTEs were evaluated by measuring sj-TREC by real-time PCR.The mean percentage of sj-TREC+ cells present in CP was not significantly different from that of control group (0.02319% vs 0.02338%, respectively).Our data show that naive TREC+ cells are normally represented in CP. The presence of active thymopoiesis may be the underlying mechanism resulting in continuous production of T-cells, responsible of maintaining the inflammatory process.

Liquefaction experiments were carried out on an Italian subbituminous coal under CO-steam conditions, and yields of coal conversion were correlated to the extent of carbon monoxide conversion and hydrogen consumption at various reaction times to obtain information about the chemistry of coal solubilization and oil production. The results indicate that oil generation is a consequence of the slow and progressive transformation of preasphaltenes and asphaltenes that are produced in the first steps of the reaction. The oxygen and sulphur functionalities are particularly involved in this process, which requires continuous hydrogen generation via the water-gas shift reaction.

New in vitro test, the Interferon-γ assay, has now emerged for diagnosis of latent tuberculosis infection (LTBI). Newer assays based on the immune response to ESAT-6 and CFP-10 antigens from the RD1 of M. tuberculosis may have advantages over TST, in terms of higher specificity, better correlation with exposure to M. tuberculosis and less cross-reactivity due to BCG vaccination and non-TB mycobacterial infection.Two commercially available tests have been approved for the diagnosis of TB infection, the QuantiFERON® TB-Gold and the T Spot.TB. These assays are based on overlapping peptides of ESAT-6 and CFP-10; however, they do not discriminate between A-TB and LTBI. Differently, using multiepitopic peptides from ESAT-6 and CFP-10 proteins selected by quantitative implemented HLA peptide-binding motifs analysis, it has bee shown a positive response to RD1 selected peptides only in patients with A-TB.Aim of this study is to evaluate the test TB-Gold as a tool to identify TB infection in a population enrolled with suspicious active TB. Agreement between TST and Interferon-γ assay (80%), rather then sensivity and specifity was reported. Moreover the assay based on RD1 selected peptides was used to evaluate whether it would allow a discrimination between active TB and LTBI. Our study suggest, that TB-Gold is useful tool to identify TB infection in a population enrolled with suspicious active TB. Moreover the assay based on RD1 selected peptides is a useful tool to discriminate between active TB and LTBI with a positive predictive value of 100% and a negative predictive value of 76%.

Division of respiratory medicine in a specialised infectious disease hospital in Rome, Italy.Retrospective evaluation of tuberculosis (TB) care associated costs in an integrated in- and out-patient management programme.Review of the medical records of 92 human immunodeficiency virus negative TB cases admitted between September 2000 and May 2003.Length of in-hospital stay (45 +/- 35 days) was the major cost determinant, as hospitalisation accounted for almost 80% of the total costs of the case, with fixed bed-per-day charges amounting to 76% of hospital costs. Factors associated with higher costs were chest X-ray score, fever, sputum bacterial load and multidrug resistance (P0.05). Cure/treatment completion was achieved in 82% of patients entering the out-patient programme (63% of all cases). Homelessness, age and comorbidities were associated with unfavourable outcomes.A closely followed hospital-centred protocol carried out in a high-resource setting may produce acceptable cure/completion treatment rates. As a too high fraction of resources invested in TB control goes toward hospital costs, out-patient treatment strategies should be implemented.

Although more than two decades has passed since the first clinical description of the acquired immunodeficiency syndrome (AIDS) and the identification of its causative agent, the human immunodeficiency virus (HIV), the number of people living with this infection continues to rise. Today there is no part of the world that has not been affected by the HIV/AIDS epidemic. The extent of the infection throughout the world, however, varies greatly. The worst of the epidemic is now centred in developing countries, especially sub-Saharan Africa, accounting for around three-quarters of the overall HIV-related deaths, and two-thirds of all people living with HIV/AIDS. In addition, the incidence of new infections is growing in other areas such as Eastern Europe and parts of Asia. The dynamics of the pandemic also varies in the different parts of the world, and to date, only in sub-Saharan Africa has a pattern of spread to the general population been recorded.1

Our research aimed to describe infectious disease mortality in Italy between 1969 and 1999, with particular emphasis on sex, age, and geographic differences. Using mortality data provided by the Italian Central Institute for Statistics (ISTAT), we evaluated all codes of the ICD8 and ICD9 classifications to identify each cause of death attributable to infectious agents. Deaths for HIV/AIDS were excluded. Infectious diseases accounted for 1.7% of overall mortality between 1969-1999, and our approach identified 57.5% of all deaths from infections not included in the ICD8 and ICD9 infectious disease codes. Up to 1994, the mortality for all infectious diseases showed a very strong downward trend, with a 6-fold decline. This trend levelled off in 1995-1999, mainly due to increasing deaths due to septicaemias, heart infections and hepatitis. An increasing proportion of deaths due to infectious diseases occurred in the elderly, from 48.1% in 1969-1979 to 77.3% in 1990-1999. Mortality rates were consistently higher in men than in women and showed a substantial geographic heterogeneity. In the newborn, mortality rates declined 10-fold and an inverse north-south geographic gradient persisted during the study period. This exhaustive methodological approach to identifying infectious causes of deaths allows us to better define the burden of infections on mortality and register downward trends similar to those found in other industrialized countries.

As Mycobacterium tuberculosis isolation rates in tuberculous effusions are relatively low, several biochemical and immunological markers have been proposed to diagnose tuberculous pleurisy including adenosine deaminase (ADA) and interferon-gamma (IFN-gamma). Here we summarise the literature on ADA and IFN-gamma as predictors of tuberculous pleurisy.After a systematic review of English language studies, we used summary receiver operating characteristic curve (SROC) analysis to determine the cumulative diagnostic accuracy of both markers and Bayes' theorem to calculate post-test probability of disease in settings with different prevalences of tuberculous pleurisy, assessed and reported the quality of primary studies.From 1978 to November 2000, studies containing sufficient data for the determination of both sensitivity and specificity were 31 on ADA, including 4738 patients, and 13 on IFN-gamma, including 1189 patients. SROC curve yielded a maximum joint sensitivity and specificity of 93% for ADA and 96% for IFN-gamma. In the setting of tuberculous effusion prevalence of 5%, 25% and 85%, post-test probability of a negative ADA test were 0.4%, 2.4% and 24%, and 0.22%, 1.2% and 17% for a negative IFN-gamma test.With the caveat that limitations in the design of the studies summarised here may distort estimates of test performance, ADA and IFN-gamma appear to be reasonably accurate at detecting TB pleurisy.