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Summary A low count of CD4+ and CD8+ lymphocytes is a hallmark laboratory finding in the Coronavirus disease 2019 (COVID‐19). Using flow cytometry, we observed significantly higher CD95 (Fas) and PD‐1 expression on both CD4+ T and CD8+ T cells in 42 COVID‐19 patients when compared to controls. Higher CD95 expression in CD4+ cells correlated with lower CD4+ counts. A higher expression of CD95 in CD4+ and CD8+ lymphocytes correlated with a lower percentage of Naive events. Our results might suggest a shift to antigen‐activated T cells, expressing molecules increasing their propensity to apoptosis and exhaustion during COVID‐19 infection.

Background Infective endocarditis (IE) is characterized by high rates of in-hospital death, and Staphylococcus aureus infection predicts a worse prognosis. We aimed to assess if admission inflammatory biomarkers (white blood cell – WBC – count, C-reactive protein — CRP, and procalcitonin) are informative on microbiological etiology and short-term outcomes. Methods Data from 236 patients admitted for IE from January 2013 to June 2018 were retrieved from a multicenter registry. Results Fifty-two patients (22%) were infected by S. aureus. WBC, CRP and procalcitonin had area under the curve (AUC) values for S. aureus infection of 0.595, 0.675, and 0.727, respectively. Adding procalcitonin to WBC improved discrimination over WBC alone (p = 0.045), and procalcitonin predicted S. aureus infection independently from the other inflammatory biomarkers and patient characteristics. Patients with WBC ≥ 12,800/mm3, CRP ≥ 130 mg/L, and procalcitonin ≥ 1.7 ng/mL had an almost 20-fold higher risk of S. aureus infection than patients with all biomarkers Conclusions Among patients with IE, high levels of inflammatory biomarkers on admission, particularly procalcitonin, are associated with a higher likelihood of S. aureus infection, and a higher risk of in-hospital mortality.

To investigate the prognostic role of procalcitonin (PCT) assessment and blood culture (BC) acquisition in the emergency department (ED) in patients with urinary tract infection (UTI) or urosepsis. We enrolled patients admitted for UTI to our ED over a 10-year period. Mortality and in hospital length of stay (LOS) were compared between patients with UTI or urosepsis who had sampling for PCT levels and BC taken in the ED (ePCT group-eBC group) and those who had not (no-ePCT group-no-eBC group). 1029 patients were analyzed, 52.7% of which were female. Median age was 77 [65-83]; 139 patients (13.5%) had complicated UTI. Median LOS was 10 [7-17] days. In the ePCT group, LOS was 10 [7-16] days, vs. 10 [7-17] (p = 0.428) in the no-ePCT group. In the eBC group, LOS was 10 [6-16] days vs. 10 [7-17] days (p = 0.369) in the no-eBC group. The overall mortality rate was 6.6%. The mortality rate was not affected by early PCT determination (6% in the ePCT group vs. 6.9% in the no-ePCT group, p = 0.584). Similarly, the mortality rate was not different in the eBC group as compared to the no-eBC group (5.4% vs. 6.9%, p = 0.415). Performance of ePCT or eBC testing made no significant difference in terms of improvement of mortality rates in septic patients (11.4% vs. 7.2%; p = 0.397 and 8.8% vs. 9.8%; p = 0.845, respectively). The prognostic relevance of early evaluation of PCT and BC in the ED of patients with febrile UTI appears limited. In complicated UTI patients, PCT and BC testing may be more appropriate in the context of improving antibiotic stewardship, or as an integral component of PCT-guided standardized protocols.

Background and Objectives: Fever is one of the most common presenting complaints in the Emergency Department (ED). The role of serum procalcitonin (PCT) determination in the ED evaluation of adults presenting with fever is still debated. The aim of this study was to evaluate if, in adults presenting to the ED with fever and then hospitalized, the early PCT determination could improve prognosis. Materials and Methods. This is a retrospective, mono-centric study, conducted over a 10-year period (2009–2018). We analyzed consecutive patients ≥18 years admitted to ED with fever and then hospitalized. According to quick sequential organ failure assessment (qSOFA) at admission, we compared patients that had a PCT determination vs. controls. Primary endpoint was overall in-hospital mortality, secondary endpoints were in-hospital length of stay, and mortality in patients with bloodstream infection and acute respiratory infections. Results. The sample included 12,062 patients, median age was 71 years and 55.1% were men. In patients with qSOFA ≥ 2 overall mortality was significantly lower if they had a PCT-guided management in ED, (20.5% vs. 26.5%, p = 0.046). In the qSOFA &lt, 2 group the mortality was not significantly different in PCT patients, except for those with a final diagnosis of bloodstream infection. Conclusions. Among adults hospitalized with fever, the PCT evaluation at ED admission was not associated with better outcomes, with the possible exception of patients affected by bloodstream infections. However, in febrile patients presenting to the ED with qSOFA ≥ 2, the early PCT evaluation could improve the overall in-hospital survival.

Objectives Surgical antibiotic prophylaxis (SAP) represents a major indication of antibiotic consumption worldwide. The present study aims to report the results of an enabling, long-term AMS intervention conducted between 2013 and 2019 on an Italian University Hospital performing more than 40.000 surgical interventions per year. Methods SAP inappropriateness was defined according to the ASHP guidelines and divided in four main categories: indication, selection and dosing, duration, timing. Between 2013 and 2019, we conducted a continuative AMS intervention over 14 surgical departments that included enablement, review of selected clinical records and feedback. Results We collected a total of 789 SAP prescribed to 735 patients (mean age 56.7 ± 17.8y). Overall, guideline adherence improved from 36.6% (n = 149) at baseline to 57.9% (n = 221) post-intervention (P P indication (from 58.5 to 93.2%), selection and dosing (from 58.5 to 80.6%), timing (from 92.4 to 97.6%), duration (from 71 to 80.1%). Conclusions Though results cannot be generalized to all hospital populations, enabling AMS interventions may be effective in establishing a sustained improvement in SAP appropriateness rates. Once identified the main causes of SAP inappropriateness, tailored AMS interventions for each department may be beneficial. Further studies are needed to evaluate specific outcomes as incidence of surgical site infections and antimicrobial resistance.

Background and aims There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death. Methods and results Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6–14.7 for age ≥85 vs 18–44 y); HR = 4.7; 2.9–7.7 for estimated glomerular filtration rate levels, Highlights • Impaired renal function, elevated C-reactive protein and advanced age were major indicators of death in COVID-19 patients. • These associations were substantially homogenous across all sub-groups analysed. • No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. • Death rates were higher in the Northern as opposed to Central-Southern Italian regions.

Since the beginning of COVID-19 pandemic, clinical, radiological and histopathological features consistent with viral-induced organizing pneumonia (OP) have been reported as hallmark characteristics of the disease. Here, we describe the case of ten patients with severe COVID-19 pneumonia treated with methylprednisolone 1mg/kg for showing clinical and radiological features suggestive of OP at least 20 days after symptom onset and despite standard treatment for COVID-19.

The Fungitell assay (FA) and the Wako β-glucan test (GT) are employed to measure the serum/plasma 1,3-β-D-glucan (BDG), a well-known invasive fungal disease biomarker. Data to convincingly and/or sufficiently support the GT as a valuable alternative to the FA are yet limited. In this study, we evaluated the FA and the GT to diagnose invasive aspergillosis (IA), invasive candidiasis (IC), and Pneumocystis jirovecii pneumonia (PJP). The FA and GT performances were compared in sera of patients with IA (n = 40), IC (n = 78), and PJP (n = 17) with respect to sera of control patients (n = 187). Using the manufacturer's cutoff values of 80 pg/mL and 11 pg/mL, the sensitivity and specificity for IA diagnosis were 92.5% and 99.5% for the FA and 60.0% and 99.5% for the GT, respectively; for IC diagnosis were 100.0% and 97.3% for the FA and 91.0% and 99.5% for the GT, respectively; for PJP diagnosis were 100.0% and 97.3% for the FA and 88.2% and 99.5% for the GT, respectively. When an optimized cutoff value of 7.0 pg/mL for the GT was used, the sensitivity and specificity were 80.0% and 97.3% for IA diagnosis, 98.7% and 97.3% for IC diagnosis, and 94.1% and 97.3% for PJP diagnosis, respectively. At the 7.0-pg/mL GT cutoff, the agreement between the assays remained and/or became excellent for IA (95.1%), IC (97.3%), and PJP (96.5%), respectively. In conclusion, we show that the GT performed as well as the FA only with a lowered cutoff value for positivity. Further studies are expected to establish the equivalence of the two BDG assays.

Coronavirus disease 2019 (COVID-19) has afflicted tens of millions of people, fostering and unprecedent effort in vaccine development and distribution. Healthcare workers (HCW) play a key role in vaccine promotion and patient guidance, and it is likely that hesitancy among this population will have a major impact on the adoption of a successful immunization policy. To investigate HCW attitudes towards anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccination, we developed an anonymous online cross-sectional survey. 1723 Italian HCW responded. Overall, 1155 (67%) intended to be vaccinated, while 443 (26%) were not sure and 125 (7%) declared refusal. In multivariate analysis, factors associated with hesitancy were using Facebook as the main information source and being a non-physician HCW, while predictors of acceptance included younger age, being in close contact with high-risk groups and having received flu vaccination during the 2019–2020 season. Reasons for hesitancy included lack of trust in vaccine safety (85%) and receiving little (78%) or conflicting (69%) information about vaccines. According to our results, adequate investment in vaccine education for healthcare personnel appears to be urgently needed, prioritizing non-physicians and information quality spread through social media. We hope that our data could help governments and policy-makers to target communication in the ongoing COVID-19 vaccination campaign.

Objective Antibiotic prophylaxis (AP) is useful to prevent antimicrobial overuse, misuse and abuse, as well against the occurrence of surgical site infections (SSIs). This study aimed to describe the implementation of a quality improvement intervention on AP for elective surgery, as informal interviews showed a lower than expected compliance with internal recommendations, and to evaluate intervention's effect in terms of main drug consumption. Design A quality improvement intervention on all elective cases within 14 main surgical departments was performed. SQUIRE 2.0 guidelines were used in designing and reporting. Setting The intervention was implemented in an Italian Teaching Hospital 2 years after the adoption of internal evidence-based AP recommendations. Participants Professionals involved in elective surgery. Intervention(s) The intervention was structured into two phases: a survey was conducted during two non-consecutive weeks period (April–May 2013) to assess the adherence to the international guidelines in AP; survey's results were presented and discussed with all the surgical teams (December 2013–April 2014). Main outcome measure(s) Impact on cefazolin consumption (in defined daily doses per 100 procedures). Results Data of AP for 653 surgical procedures in terms of type, timing, duration, excess and defect were analyzed. An optimal AP rate resulted in 48.1% cases. Reduction in cefazolin use (−21.5%) and cost (−22.9%) was registered. Conclusions Though results cannot be generalized to all hospital populations, the implemented intervention is likely to improve AP consequently improving quality of care and reducing costs. Further studies are needed to evaluate specific outcomes such as rate of SSIs and antibiotic resistance.

The Raltegravir Switch for Toxicity or Adverse Events (RASTA) Study is a 2-arm randomized pilot study exploring the safety and efficacy at 48 weeks of a treatment switch to raltegravir associated with tenofovir/emtricitabine or abacavir/lamivudine in patients with regimens with optimal virological control.Patients treated with stable protease inhibitor (PI)-, non-nucleoside reverse transcriptase inhibitor (NNRTI)-, or nucleoside reverse transcriptase inhibitor (NRTI)-based regimens, with HIV-RNA levels50 copies/ml for ≥ 3 months and a CD4 cell count200 cells/μl were eligible. Enrollment of 40 patients was planned: at baseline patients were randomized 1:1 to switch to raltegravir plus tenofovir/emtricitabine (arm A) or abacavir/lamivudine (arm B). Laboratory parameters, raltegravir plasma levels, self- reported adherence, quality of life parameters, neurocognitive performance, bone composition, and body fat distribution were monitored. Virological failure was defined as HIV-RNA50 copies/ml on 2 consecutive determinations.After 48 weeks, 5/40 (12.5%) regimen discontinuations occurred: 2 were for low-level viremia virological failure (both in arm A, at weeks 24 and 48) and 3 were for adverse events (neurological disturbances and skin rash in arm B; proximal tubulopathy in arm A). Overall, a significant CD4 increase was observed at weeks 36 and 48, and a significant decrease in total cholesterol, non-high density lipoprotein cholesterol, and triglycerides was observed at each study visit. Physical health/satisfaction in therapy scores and neuropsychological performance improved. The lumbar column Z-score improved, with no modification in other bone composition and fat distribution parameters.The investigated switch strategy was associated with rare virological failure. Improvements in lipid levels, quality of life measures, neuropsychological performance, and bone composition suggest good tolerability of raltegravir-based regimens.

In order to analyze the clinical relevance of the pharmacokinetic interactions between vinblastine and antiretrovirals described in literature, we evaluated all HIV-infected patients with Hodgkin's lymphoma treated with vinblastine-containing regimens and combination antiretroviral therapy, in a single clinical center. The use of protease inhibitors was independently associated with WHO grade III-IV neutropenia. Moreover, an inverse correlation between dosage of ritonavir and mean nadir neutrophil count was found. The concomitant administration of vinblastine-containing chemotherapy regimens with protease inhibitors can lead to higher levels of neutropenia than those of different classes of drugs such as nonnucleoside reverse transcriptase inhibitors or integrase inhibitors.

Primary intrahepatic lithiasis is defined by the presence of gallstones at the level of cystic dilatations of the intrahepatic biliary tree. Liver resection is considered the treatment of choice, with the purpose of removing stones and atrophic parenchyma, also reducing the risk of cholangiocarcinoma. However, in consequence of the considerable incidence of infectious complications, postoperative morbidity remains high. The current study was designed to evaluate the impact of preoperative bacterial colonization of the bile ducts on postoperative outcome. The clinical records of 73 patients treated with liver resection were reviewed and clinical data, operative procedures, results of bile cultures, and postoperative outcomes were examined. Left hepatectomy (38 patients) and left lateral sectionectomy (19 patients) were the most frequently performed procedures. Overall morbidity was 38.3 %. A total of 133 microorganisms were isolated from bile. Multivariate analysis identified previous endoscopic or percutaneous cholangiography (p = 0.043) and preoperative cholangitis (p = 0.003) as the only two independent risk factors for postoperative infectious complications. Postoperative morbidity was strictly related to the preoperative biliary infection. An effective control of infections should be always pursued before liver resection for intrahepatic stones and an aggressive treatment of early signs of sepsis should be strongly emphasized.

To assess the risk of clinical progression (CP) according to the duration of time spent without complete viral load (VL) suppression compared with that associated with periods of stably suppressed viremia in HIV-infected people who started highly active antiretroviral therapy (HAART) when previously naïve to antiretrovirals.A cohort study of patients having started HAART after enrollment in the Italian Cohort of Antiretroviral-Naive Patients (ICoNA) and being followed for at least 6 months.Person-years spent in different categories according to the VL level and the change in VL from the most recent value before the initiation of HAART were calculated. A multivariable Poisson regression model, including potential confounders, was constructed.A total of 3023 patients were studied. The overall rate of CP was 13.4 per 1000 person-years. Evidence for a higher risk of CP was observed for people with a current VL10,000 copies/mL. For each year longer spent on HAART with a VL100,000 copies/mL, a 5-fold increased risk was observed (relative risk [RR] = 5.34, 95% confidence interval [CI]: 2.83 to 1.08; P = 0.0001). An increased risk of CP in patients with current suppression1.5 log10 copies/mL (RR = 2.34, 95% CI: 1.16 to 4.74; P = 0.02) and in those with no suppression or a VL higher than their set point (RR = 2.39, 95% CI: 1.17 to 4.89; P = 0.02) was observed compared with those with suppression of3 log10 copies/mL, although it was not significant. Longer duration on HAART with a VL suppressed below set point seemed to confer protection against CP.Virologic failure to antiretroviral drugs is common. The risk of CP may remain low despite a low but detectable level of HIV viremia.

The association of depressive symptoms, neurocognitive impairment, and adherence to highly active antiretroviral therapy (HAART) was evaluated in 135 HIV-infected persons. Thirty percent reported nonadherence to HAART. Depressive symptoms (assessed with the Montgomery-Asberg Depression Rating Scale) and neurocognitive impairment (assessed with a neuropsychological test battery) were documented in 24% and 12%, respectively, of the study participants. Nonadherence to HAART was independently associated with worse depression rating scale scores (odds ratio=1.05, 95% confidence interval [CI]=1.00-1.10), acquisition of HIV through injection of drugs (odds ratio=2.59, 95% CI=1.05-6.39), and complaints about impairment of sexual activity (odds ratio=6.62, 95% CI=1.16-37.6). The presence of depressive symptoms, but not neurocognitive impairment, was associated with nonadherence.

The objective of the study was to determine the association of neurocognitive impairment with health-related quality of life (HRQoL) in patients receiving highly active antiretroviral therapy (HAART). Seventy subjects were cross-sectionally analysed with a standardized neuropsychological test battery and a questionnaire including an Italian translation of the MOS-HIV Health Survey. The presence of neurocognitive impairment was significantly associated with lower HRQoL scores: pain ( P = 0.03), physical functioning ( P = 0.01), role functioning ( P = 0.01), social functioning ( P = 0.029), mental health ( P = 0.001), energy ( P = 0.036), health distress ( P = 0.002), cognitive functioning ( P = 0.05), current health perception ( P Neurocognitive impairment in patients receiving HAART was associated with reduced HRQoL. Identifying cognitive impairment may provide motivation for additional treatment to help patients to compensate for deficits in functioning.

The alterations occurring in the intestinal flora during Clostridium difficile infection (CDI) may promote the translocation of Candida to the blood and the development of candidaemia. The aim of our study was to analyse clinical findings of these patients to determine the risk factors associated with the development of candidaemia subsequent to CDI. We compared 35 patients with candidaemia subsequent to CDI with 105 patients with CDI. Patients with candidaemia showed more severe infections and higher mortality. The ribotype 027 strain and vancomycin treatment at ≥1000 mg/day were prevalent in patients developing candidaemia. CDI may predispose to the translocation of Candida .

To analyze the clinical efficacy of cidofovir combined with highly active anti-retroviral therapy (HAART) in AIDS-related progressive multifocal leukoen-cepalopathy (PML), a multicenter observational study was performed. Consecutive HIV-positive patients with histologically or virologically proven PML and at least 4 weeks of treatment after diagnosis were examined: 27 patients were treated with HAART, whereas 16 patients were treated with HAART plus cidofovir 5 mg/kg intravenously per week for the first 2 weeks and every other week thereafter. JC virus DNA was quantified in cerebrospinal fluid (CSF) by PCR. Baseline virologic, immunologic, and clinical characteristics as well as HIV RNA and CD4 responses to HAART were homogeneous between the groups. The median follow-up was 132 weeks. In one case (6%), cidofovir was permanently discontinued because of severe proteinuria. One-year cumulative probability of survival was 0.61 with cidofovir and 0.29 without (log rank test P = 0.02). After adjusting for baseline CD4 counts, JC viral load in CSF, Karnofsky, and use of HAART prior to the onset of PML, the use of cidofovir was independently associated with a reduced risk of death (hazard ratio, 0.21, 95% confidence interval, 0.07–0.65; P = 0.005). A randomized study will definitively establish whether cidofovir confers significant advantage over HAART alone in AIDS-related PML.

Article abstract-Objective: To identify disease patterns in AIDS-related focal brain lesions (FBL) and to design a decision-making strategy for differential diagnosis. Design: Prospective study. Probabilities of CNS disorders were calculated using Bayes' theorem according to clinical variables (mass effect at CT or MRI, Toxoplasma serology, anti-Toxoplasma prophylaxis) and to the results of polymerase chain reaction (PCR) assays. Patients: 136 consecutive HIV-infected patients with a definitive diagnosis of FBL-causing disorder observed from 1991 to 1995 in a single clinical setting. Interventions: Patients underwent empiric anti-Toxoplasma therapy. After 3 weeks, patients with progressive/stable disease underwent brain biopsy. In 66 patients Epstein-Barr virus (EBV)-DNA, JC virus (JCV)-DNA, and T gondii-DNA amplification was performed by PCR in CSF. Diagnostic criteria were histopathologic examination of bioptic or autoptic tissue specimens for all disorders and complete/partial resolution of FBL after empiric therapy for toxoplasmic encephalitis (TE). Results: Neuroradiologic characteristics did not discriminate between TE and primary CNS lymphoma (PCNSL). Probability of TE was 0.87 in Toxoplasma-seropositive patients with mass effect who were not receiving anti-Toxoplasma prophylaxis, but only 0.59 if prophylaxis was performed. In seronegative patients with mass effect, the likelihood of PCNSL was 0.74. If EBV-DNA or T gondii-DNA tests were positive, the probability of PCNSL or TE increased to more than 0.96. The absence of T gondii-DNA did not exclude the possibility of a TE diagnosis. Among FBL without mass effect, the probability of progressive multifocal leukoencephalopathy (PML) was 0.81; this increased to 0.99 if JCV-DNA testing was positive. Sensitivity of brain biopsy was 93%, with a perioperative morbidity of 12% and a mortality of 2%. Conclusions: Due to the low diagnostic capability of clinical variables, PCR amplifications in CSF, especially for EBV-DNA and for JCV-DNA, represent, in most cases, an essential step in the differential diagnosis of AIDS-related FBL. This is particularly true in patients with FBL without mass effect or with mass effect and who are either seronegative or undergoing anti-Toxoplasma prophylaxis. Brain biopsy remains a necessary procedure in EBV-DNA-positive cases and in seronegative patients with FBL displaying a mass effect. Positive JCV-DNA testing may obviate the need for brain biopsy in patients with FBL without mass effect. An advanced diagnostic strategy based on combined clinical criteria and PCR tests may allow rapid and accurate identification of patients for prompt brain biopsy or specific therapy.NEUROLOGY 1997;48: 687-694

OBJECTIVES To explore 48 week safety and efficacy of treatment simplification to atazanavir/ritonavir + lamivudine in HIV-infected patients with virological suppression on a stable atazanavir/ritonavir-based standard triple regimen. METHODS This was a single-arm pilot study, enrolling 40 patients on atazanavir/ritonavir + two nucleos(t)ide reverse transcriptase inhibitors (NRTIs), without previous treatment failure, with HIV-RNA 3 months and CD4 >200 cells/mm(3). At baseline, patients were switched to 300/100 mg of atazanavir/ritonavir + 300 mg of lamivudine once daily. Laboratory parameters, atazanavir plasma levels, self-reported adherence, quality of life, neurocognitive performance, bone composition and body fat distribution were monitored. Virological failure was defined as HIV-RNA >50 copies/mL on two consecutive determinations or a single level >1000 copies/mL. RESULTS After 48 weeks, 4/40 (10%) regimen discontinuations occurred: 1 death (brain haemorrhage), 1 study withdrawal (inadequate atazanavir plasma levels), 1 re-induction with two NRTIs due to pregnancy and 1 virological failure without development of resistance. Seven moderate to severe adverse events were recorded (including four renal colics, possibly treatment-related) in six patients. At week 48, increases in total (mean change +17 mg/dL, P = 0.001), high-density lipoprotein (+6 mg/dL, P

Background The objective of our study was to compare two different central nervous system penetration- effectiveness (CPE) scores for the prediction of cognitive dysfunction in HIV-infected patients. Methods We performed a cross-sectional single cohort study, consecutively enrolled during routine outpatient visits. HIV-infected subjects on antiretroviral therapy with plasma HIV RNAResults A total of 101 patients were enrolled (66% male, median age 47 years, median education 13 years); mean adherence was 81%. orCPE rank ≥1.5 and revCPE rank ≥6 were observed in 85.0% and 78.2% of patients, respectively ( P=0.31). Asymptomatic neurocognitive impairment (ANI) was diagnosed in 50 (49.5%) subjects. In a multivariable model, after adjusting for nationality, adherence and nadir CD4+ T-cell count, orCPE rank did not show an association with cognitive performance ( P=0.704). By contrast, patients with revCPE rank ≥6 (OR 0.32, 95% CI 0.11, 0.95; P=0.039) and adherence ≥80% (OR 0.39, 95% CI 0.15, 0.99; P=0.047) showed a decreased risk of cognitive impairment. Conclusions A high prevalence of ANI was observed in virologically suppressed HIV-infected individuals. The revCPE rank showed improved association with neurocognitive dysfunction over the orCPE rank. Moreover, a relationship between cognitive impairment and adherence to antiretroviral therapy was found.

Summary Background Whether people living with HIV who have not received antiretroviral therapy (ART) and have high CD4 cell counts have higher mortality than the general population is unknown. We aimed to examine this by analysis of pooled data from industrialised countries. We merged data on demographics, CD4 cell counts, viral-load measurements, hepatitis C co-infection status, smoking status, date of death, and whether death was AIDS-related or not from 23 European and North American cohorts. We calculated standardised mortality ratios (SMRs) standardised by age, sex, and year, stratifying by risk group. Data were included for patients aged 20-59 years who had at least one CD4 count greater than 350 cells per μL while ART naive. All pre-ART CD4 counts greater than 350 cells per μL from January, 1990, to December, 2004, were included. We investigated mortality for four risk groups - men who have sex with men, heterosexual people, injecting drug users, and those at other or unknown risk. The association between CD4 cell count and death rate was investigated by use of Poisson regression methods. Data were analysed for 40 830 patients contributing 80 682 person-years of follow-up. Of 419 deaths, 401 were used in the SMR analysis: 100 men who have sex with men (SMR 1·30, 95 CI 1·06-1·58); 68 heterosexual people (2·94, 2·28-3·73); 203 injecting drug users (9·37, 8·13-10·75); and 30 in the other or unknown risk category (4·57, 3·09-6·53). Compared with CD4 counts of 350-499 cells per μL, death rate was lower in patients with counts of 500-699 cells per μL (adjusted rate ratio 0·77, 95 CI 0·61-0·95) and counts of 700 cells per μL (0·66, 0·52-0·85). In HIV-infected ART-naive patients with high CD4 cell counts, death rates were raised compared with the general population. In men who have sex with men this was modest, suggesting that a substantial proportion of the increased risk in other groups is due to confounding by other factors. Even though the increased risk is small, new studies of potential benefits of ART in this group are merited. European Commission, FP6. European AIDS Treatment Network (NEAT). Project number LSHP-CT-2006-037570.

Objective: To evaluate deaths from AIDS-defining malignancies (ADM) and non-AIDS-defining malignancies (nADM) in the D:A:D Study and to investigate the relationship between these deaths and immunodeficiency. Design: Observational cohort study. Methods: Patients (23 437) were followed prospectively for 104 921 person-years. We used Poisson regression models to identify factors independently associated with deaths from ADM and nADM. Analyses of factors associated with mortality due to nADM were repeated after excluding nADM known to be associated with a specific risk factor. Results: Three hundred five patients died due to a malignancy, 298 prior to the cutoff for this analysis (ADM: n = 110; nADM: n = 188). The mortality rate due to ADM decreased from 20.1/1000 person-years of follow-up [95% confidence interval (CI) 14.4, 25.9] when the most recent CD4 cell count was

The impact of lipodystrophy (LD) on quality of life is high, but it has not been demonstrated in literature. The objective of the study was to assess the impact of LD on the health-related quality of life (HRQOL) in HIV-infected people on highly active antiretroviral therapy (HAART). Patients with LD phenotype defined by the Multicenter AIDS Cohort Study (MACS) were included. Three different methods were used to define LD severity: both patient and physician evaluation using the HIV Outpatient Study (HOPS) severity scales and the Lipodystrophy Case Definition (LDCD). The HRQOL was evaluated by MOS-HIV Health Survey. Four hundred one patients on HAART for a mean of 108 +/- 52 months were evaluated for LD at the Metabolic Clinic of Modena and Reggio Emilia University were enrolled from January 2003 to July 2006. According to self-perceived or physician-based HOPS, 106 (26.5%) and 122 (30.4%) patients had severe LD. Females had significantly more severe LD. Few HRQOL scores correlated to LD severity using the physician-based score (both HOPSph and LDCD), while all the HRQOL scores correlated with LD severity when a patient-based score was used (HOPSpt). In multiple linear regression analysis, Mental Health HRQOL score, gender, body mass index, age, body image satisfaction were independent predictors of patient-based (HOPSpt) LD, while none of the HRQOL scores, but female gender, age, waist-to-hip ratio, limb fat, and body image satisfaction were correlated with physician-estimated HOPSph LD severity. HRQOL was strongly correlated with LD severity when a patient-based score was used. For an overall assessment of the impact of LD on HIV-infected people, both patient-based and physician-based measures are required.

Background Both psychological and organic factors have been recognized to be associated with sexual dysfunction in HIV-infected individuals. Methods In this cross-sectional study we evaluated the prevalence and factors associated with sexual dysfunction in a cohort of HIV-infected adult men. Evaluation tools included: the International Index of Erectile Function (erectile dysfunction [ED], desire, orgasm, intercourse satisfaction, overall satisfaction), the Assessment of Body Change and Distress (body image satisfaction), the Medical Outcomes Study HIV Health Survey (mental and physical health-related quality of life), and plasma free and total testosterone level (hypogonadism). Results Three-hundred and fifty-seven men were enrolled. Among 336 patients reporting sexual activities in the 4 weeks before, 94 (29.6%) had mild, 30 (9.4%) moderate and 34 (10.1%) severe dysfunction. The Mental Health Summary score was 2.28 units (95% confidence interval [CI] 1.51, 3.06) lower for each unit higher of body image dissatisfaction and 0.31 units (95% CI 0.27, 0.36) higher for each unit higher of the score for body change interference with habits. At regression analysis, ED was independently related to the body mass index (B=0.31, 95% CI 0.08, 0.62). Desire, orgasm and overall satisfaction domains were associated with mental health score (B=0.87, 95% CI 0.47, 1.27; B=0.75, 95% CI 0.23, 1.26; B=0.86, 95% CI 0.45, 1.28, respectively). An improved intercourse satisfaction domain was associated with a lower interference of body changes with habits and social life (B=0.39, 95% CI 0.05, 0.73). Testosterone, metabolic alterations and HAART were not associated with sexual function domains. Conclusions Body image and mental health but not HAART or hypogonadism were associated with sexual function domains.

Objective: To design a Health-related Quality of Life (HRQoL) instrument for HIV-infected people in the era of highly active antiretroviral therapy (HAART). Methods: The self-administered questionnaire was developed by an Italian network including researchers, physicians, people living with HIV, national institutions and community-based organizations (CBO) through several steps: (1) review of existing HRQoL literature and questionnaires for HIV-infected people; (2) selection of relevant domains measuring HRQoL in HIV-infected people, and identification of new domains related to new aspects of HRQoL concerning HAART-treated individuals; (3) conduction of two pre-test analyses in independent groups of Italian HIV-positive people (n≌100) distributed throughout the country. The objectives of the first pre-test were to verify the usefulness of the questionnaire, to construct a form easily understandable by everyone, to define the domains and their significance; the second pre-test aimed at evaluating and reshaping the questionnaire based on a statistical analysis of the outcomes of first pre-test; (4) validation analysis. A large cohort of people with HIV infection was recruited for the last step.Results: The internal consistence reliability (Cronbach’s α) was ≥0.70 for all domains. Most domains had Cronbach’s coefficient >0.80. All domains demonstrated convergent and discriminant validity. The final version of ISSQoL includes two sections: HRQoL Core Evaluation Form (9 domains) and Additional Important Areas for HRQoL (6 domains). The ISSQoL was administered together with two additional forms: a Daily Impact of Symptoms Form and a Demographic Information Form. The Additional Important Areas for HRQoL include social support, interaction with medical staff, treatment impact, body changes, life planning, and motherhood/fatherhood.Conclusion: The data reported in the present paper provide preliminary evidence of the reliability and validity of the ISSQoL questionnaire for the measurement of HRQoL in HIV-infected people. The direct involvement of HIV-positive people in all the phases of the project was a key aspect of our work.

Lipodystrophy (LD) includes morphologic changes that are distressing to patients with HIV. We tested the validity of an Italian version of the Assessment of Body Change and Distress (ABCD) questionnaire and analysed its relationship to physical and mental aspects of Health-Related Quality of Life. Two hundred and fifty-two patients completed the questionnaires. Construct validity of the ABCD was tested against the MOS-HIV Health Survey, body mass-index (BMI) and CD4+ T-lymphocyte counts. Cronbach's alpha for the ABCD total score was 0.94. The ABCD showed the hypothesized moderate correlations to MOS-HIV scales and clinical variables. Preliminary evidence supports the reliability and validity of the Italian version of the ABCD in people with HIV and LD. This questionnaire may be useful to identify people experiencing greater impact of LD, or to evaluate the impact of interventions to treat LD such as plastic surgery.

In order to verify whether fluconazole has a prophylactive effect against the occurrence of cryptococcosis in HIV-infected patients and to identify other factors capable of increasing or reducing the risk of this infection, we arranged a case-control study of 17 patients with cryptococcal infection. 34 controls were selected, matched by presence of an AIDS-defining event, CD4 cell count, and date of T-cell phenotyping. No significant difference in exposure to fluconazole, in total days of treatment, or in total dose administered was observed between cases and controls. However, control patients took a significantly higher average daily dosage of fluconazole and a linear tendency in risk reduction (p = 0.04) in relation to increasing dosage was observed. Antiretroviral therapy and an average daily fluconazole dose exceeding 150 mg both each reduced the risk of a cryptococcal infection.

In the era of new antiretroviral treatments that have dramatically reduced both morbidity and mortality, a primary goal is to maximize function and wellbeing in the everyday life of HIV-infected patients. To be able to do so, it would be important for clinicians and policy makers to identify factors that influence health-related quality of life (HRQoL). The objective of this multicentre prospective cohort study was to identify determinants of HRQoL in a cohort of Italian HIV-infected patients, the majority of whom were taking highly active antiretroviral therapy (HAART). A total of 809 patients were enrolled. The MOS-HIV Health Survey (summarized using two scores, physical health (PHS) and mental health (MHS)), and an HIV-related symptom scale were administered at enrolment and six months later. At baseline, low CD4+ cell count, hospitalization during the three months before the enrollment and symptoms were independently related to poor PHS; hospitalization during the three months before the enrollment, symptoms and poor satisfaction with information from providers were independently related to MHS. Predictors of PHS at six months included the stage of HIV infection, baseline CD4+ cells count, PHS and symptom score; while age, baseline MHS, symptom score and education predicted six-month MHS. Among these factors, symptoms, recent hospitalization and satisfaction with information are most amenable to clinical intervention.

We examined the relationship of HIV-related cognitive impairment and health-related quality of life (QoL). Subjects were administered measures of cognitive function (a battery of 17 neuropsychological tests) and of QoL (the MOS-HIV questionnaire). Study measures also included comprehensive clinical and neurological evaluation, laboratory testing, and brain imaging studies in patients with impaired neuropsychological evaluation. One-hundred and eleven subjects were examined. Cognitively impaired patients (33.3%) reported poorer QoL scores in all domains (p < 0.05): physical health summary score (PHS) (44.6 vs. 49.9), mental health summary score (MHS) (37.7 vs. 44.4), pain (67.6 vs. 79.4), physical functioning (75.9 vs. 87.7), role functioning (32.4 vs. 41.5), social functioning (70.3 vs. 83.5), mental health (48.2 vs. 61.0), energy (53.1 vs. 63.0), health distress (60.8 vs. 75.5), cognitive functioning (CF) (60.5 vs. 71.8), general health perceptions (29.2 vs. 43.4), and QoL (36.5 vs. 47.0). The number of altered neuropsychological tests correlated significantly with MHS (p < 0.001), PHS (p < 0.03), CF (p < 0.02), and QoL (p < 0.02) scores. A correlation between seven of seven neuropsychological measures exploring speed of mental processing, three of four exploring mental flexibility, four of six exploring memory, and two of two exploring fine motor functioning and MHS, PHS, CF, or QoL scores was also found. Poor performance on the Digit Symbol test was most strongly associated with poor MHS (OR 1.04, 95% CI 1.01-1.08, p < 0.009) and PHS (OR 1.04, 95% CI 1.01-1.08, p < 0.01) scores, controlling for CD4 count, previous AIDS diagnosis, receiving HAART, and drug abuse. Cognitive impairment is associated with poor QoL. People with more severe cognitive impairment have the highest probability of having a poor QoL. Cognitive impairment in any cognitive domain explored in our battery is also associated with poor QoL. Poor performance on the Digit Symbol Test is the strongest predictor of poor QoL.

To evaluate the association between adherence to drugs and morphologic alterations (MOA) in a cohort of HIV-infected patients on HAART.This was a cross-sectional multicenter cohort study in eight tertiary Clinical Centers of Northern and Central Italy. Consecutive outpatients taking HAART were enrolled from August 2000 to March 2001. They completed a self-administered questionnaire for the evaluation of signs of MOA and the self-reported adherence to drugs. Main outcome measures were MOA according to the Multicenter AIDS Cohort Study (MACS) definition and adherence to drugs.One hundred seventy-five persons were enrolled into the study. Median CD4 cell count was 522 (interquartile range [IQR] 306-720); 35% of people had undetectable HIV RNA. Patients had been taking HAART for a median of 53 months (IQR 33-62). Among enrolled patients, 83 (47%) had a diagnosis of self-reported MOA; 57 of them reported body changes of more than 12 months duration. Forty persons (23%) self-reported nonadherence in the previous week. Mean time on HAART was 48.7 months (SD = 19.7) for people with MOA and 42.1 months (SD = 21.8) for those without MOA (p =.043). The odds of adherence for people with MOA was 2.36 times (95% CI 1.11-5.00) higher than for people without MOA. On multivariate analysis, being older and female, having an undetectable HIV RNA, longer duration on HAART, and self-reported adherence were independently associated with the presence of MOA. In people with MOA, adherence seems to decrease over time.Longer time on HAART and self-reported adherence were correlated to MOA. MOA was also associated with older age and female gender.

To identify factors associated with cutaneous rash, we performed a retrospective multicentre analysis of HIV outpatients starting a highly active antiretroviral therapy regimen containing nevirapine. A total of 62 cutaneous adverse events were observed in 429 patients. Rash hazard was increased in women, by the prophylactic use of glucocorticoids or antihistaminics, and was reduced by escalating the initial dose of nevirapine. Women receiving glucocorticoids had a 3 month cumulative probability of rash of 0.41.

To assess rates of prescriptions of protease inhibitors (PI) and determinants of not being prescribed PIs in a cohort of HIV-infected people eligible (according to published guidelines) for highly active antiretroviral therapy (HAART).Cross-sectional survey.A total of 684 patients with CD4+ counts500 cells/microl were enrolled from seven Italian HIV treatment centers from October 1997 to April 1998. A questionnaire on health-related quality of life (MOS-HIV) and patient ratings of the quality of care was administered. Sociodemographic variables, HIV disease-related factors, and prescribed antiretroviral therapy were also recorded.61% of those enrolled were prescribed PI (median, 7.5 months). In addition, 75% of patients had previously received antiretroviral therapy. Fewer than 1% were prescribed nonnucleoside reverse transcriptase inhibitors (NNRTIs). Using multivariable logistic regression considering those with CD4+ counts500 cells/microl, patients reporting the least information received (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.23-2.58), injecting drug users (IDUs; OR, 1.73; 95% CI, 1.18-2.54), people with CD4+ counts200 cells/microl (OR, 1.76; 95% CI, 1.19-2.61), and patients with early stage disease (OR, 2.24; 95% CI, 1.73-2.90) were less likely to have be prescribed PIs.Of patients eligible for HAART, only 61% were prescribed PIs. People who wanted more information, IDUs, and patients in earlier disease stages are significantly less likely to be prescribed PIs. Access to HAART remains a critical issue in the management of HIV disease.

A multicenter analysis of 57 consecutive human immunodeficiency virus-positive patients with progressive multifocal leukoencephalopathy (PML) was performed, to identify correlates of longer survival. JC virus (JCV) DNA was quantified in the cerebrospinal fluid (CSF) by polymerase chain reaction. Two months after therapy, 4% of the patients without highly active antiretroviral therapy (HAART) and 26% with HAART showed neurologic improvement or stability (P=.03), and 8% and 57%, respectively, reached undetectable JCV DNA levels in the CSF (P=.04). One-year probability of survival was.04 without HAART and.46 with HAART. HAART and lack of neurologic progression 2 months after diagnosis were independently associated with longer survival. Among HAART-treated patients, a baseline JCV DNA

Objectives: To analyse the virological and clinical efficacy of cidofovir combined with highly active antiretroviral therapy (HAART) in AIDS-related progressive multifocal leukoencephalopathy (PML). Design: Multicentre observational study of consecutive HIV-positive patients with histologically or virologically-proven PML. Group A, 26 patients treated with HAART; group B, 14 patients treated with HAART plus cidofovir 5 mg/kg intravenously per week for the first 2 weeks and alternate weeks thereafter. JC virus DNA was quantified in cerebrospinal fluid (CSF) by PCR. Results: Baseline virological, immunological and clinical characteristics were homogeneous between the groups. In one case cidofovir was discontinued because of severe proteinuria. There was no significant difference in HIV RNA responses and changes in the number of CD4 cells between group A and B. After 2 months of therapy, five out of 12 (42%) patients from group A and seven out of eight (87%) from group B reached undetectable JC virus DNA in the CSF (Chi-square P= 0.04); moreover, 24% of group A and 57% of group B patients showed neurological improvement or stability (P= 0.038). One-year cumulative probability of survival was 0.67 with cidofovir and 0.31 without (log-rank test, P = 0.01). Variables independently associated with longer survival were the use of cidofovir, HAART prior to the onset of PML, a baseline JC virus DNA load in CSF < 4.7 log 10 copies/ml, and a baseline Karnofsky performance status ≥ 60. Conclusions: In AIDS-related PML, cidofovir added to HAART is associated with a more effective control of JCV replication, with improved neurological outcome and survival compared with HAART alone.

Detection and quantification of different Pneumocystis carinii (PC) life cycle forms were performed by polymerase chain reaction (PCR) and by morphological stains on bronchoalveolar lavage fluids (BALF) from HIV-infected patients with P. carinii pneumonia (PCP). The number of PC trophozoites was higher in patients with PCP who were receiving prophylaxis than in those not receiving prophylaxis. Also the cyst: trophozoite ratio was lower in the first group. No difference was observed between patients receiving different prophylactic medications. The imbalance between PC forms in BALF from patients with PCP receiving anti-PC prophylaxis may hamper the sensitivity of cyst stains. Multiple stains or PCR examination should be performed on BALF from patients with clinically suspected PCP who are receiving prophylaxis.

To evaluate whether the detection of Toxoplasma gondii DNA in CSF could contribute to the differential diagnosis of AIDS-related focal brain lesions, CSF samples from 88 HIV-infected patients (56 with focal brain lesions and 32 without) were tested prospectively by a nested PCR for the B1 gene of T. gondii. The assay had a detection limit of 10 trophozoite equivalents. Six of 18 patients with toxoplasmic encephalitis, but none of the 70 patients with other disorders, were PCR-positive (33.3% sensitivity and 100% specificity). Considering only those patients with cerebral toxoplasmosis from whom CSF was collected before or during the first week of antitoxoplasmic therapy, sensitivity rose to 50%. This was higher than the sensitivity in patients whose CSF was collected after the first week of treatment (odds ratio (OR) of 7.0; 95% CI: 0.46-218.2). The administration of antitoxoplasmic prophylaxis did not affect the PCR results. Patients with a poor response to therapy had a higher probability of detectable T. gondii DNA in their CSF (OR of 5.0; 95% CI: 0.37-86.6). All patients with other central nervous system disorders were PCR-negative. Despite the moderate sensitivity, the high specificity and positive predictive value (100%) make this assay a useful tool in the differential diagnosis of AIDS-related focal brain lesions as part of a series of CSF and neuroradiological examinations.

To investigate the efficacy and safety of three regimens for primary prophylaxis of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis (TE) and to evaluate their effect on survival in patients with HIV infection.Randomized, open label, prospective trial.A single Infectious Diseases Department in Italy.HIV-infected patients (n = 197) with a CD4 count200 x 10(6)/l and without previous PCP or TE.Patients were randomly assigned to receive (1) aerosolized pentamidine (AP; 300 mg monthly), (2) cotrimoxazole (CTX; 160 mg trimethoprim and 800 mg sulfamethoxazole every other day), or (3) dapsone-pyrimethamine (DP; 100 mg weekly dapsone and 25 mg biweekly pyrimethamine).PCP, TE, death, and drug-limiting toxicity. Considering difference in PCP occurrence the trial was interrupted on June 1992. Observation was prolonged until June 1994 for TE and survival.Intention-to-treat analysis yielded PCP rates of 10.2 per 100 person-years in the AP, 2.0 in the CTX, and 32.1 in the DP group [adjusted relative risk of DP versus CTX: 17.5; 95% confidence interval (CI), 2.2-139.6; P = 0.007]. TE rates in patients with positive Toxoplasma serology were 25.6 per 100 person-years in the AP, 8.9 in the CTX and 9.4 in the DP group. In 'on treatment' analysis, no episode of TE developed in the DP group, and rates were 34.7 per 100 person-years in the AP and 2.5 in the CTX group (AP versus CTX: P = 0.01; AP versus DP: P = 0.004). The adjusted risk of mortality for the DP group was 2.8 times that of the CTX group in the first part of the study (95% CI, 1.1-7.3; P = 0.037), and 1.8 times (95% CI, 1.1-2.9; P = 0.02) in the prolonged follow-up. No significant difference in the occurrence of serious adverse reactions was observed between the three treatment groups.Intermittent CTX was more effective than low-dose DP and showed a slight but not significant advantage on AP for primary PCP prophylaxis. DP was associated with a shorter survival. Both CTX and DP resulted in a significant reduction in the risk of TE.

Involvement of the central nervous system (CNS) in patients with acquired immune deficiency syndrome (AIDS) is an increasing clinical problem. The most common brain complications are toxoplasmosis (50–70 per cent), primary CNS lymphoma (20–30 per cent) and progressive multifocal leucoencephalopathy (10–20 per cent). Almost two-thirds of these conditions can be treated, early diagnosis and therapy leading to survival with a good quality of life. Although clinical and neuroradiological criteria alone may have high predictive value, they are not sufficient to distinguish the broad spectrum of diseases reliably. Consequently, biopsy appears necessary for definite diagnosis in some cases. The potential role and timing of brain biopsy have been assessed. Twenty-four of 50 human immunodeficiency virus-seropositive patients with focal cerebral lesions were considered for biopsy between October 1991 and December 1992. Twelve underwent brain biopsy, seven stereotactic and five ultrasonographically guided. A diagnosis was achieved in 11 patients: six primary lymphoma, three progressive multifocal leucoencephalopathy, and one mycotic and one tuberculous abscess. Both techniques proved to be safe and reliable, with a 92 per cent diagnostic rate. These data confirm the usefulness of biopsy in patients with AIDS with its wide range of associated cerebral lesions that require different aggressive treatments. On the basis of this preliminary experience and reports in the literature, it is considered that brain biopsy is indicated for patients with focal enhancing cerebral mass lesions seen on computed tomography and magnetic resonance imaging who do not respond to an appropriate trial of empirical antitoxoplasmosis therapy and for those showing rapid clinical deterioration in whom imaging and serology do not suggest toxoplasmosis.

Fifty-five episodes of Pneumocystis carinii pneumonia (PCP) in AIDS patients were evaluated to assess clinical and laboratory risk factors predicting the probability of surviving the acute episode of PCP and the long-term survival after PCP. Age45 yrs, PaO250 mmHg, AaPO250 mmHg, and LDH800 IU/L correlated strongly with early mortality; patients who needed mechanical ventilation had a significantly lower PaO2 and serum albumin, and higher AaPO2 and LDH compared to the patients who did not. Neither age nor PaO2, AaPO2, LDH, albumin, days from onset, time for recovery, CD4+ cell count correlated with long-term survival of AIDS patients with PCP. Informations obtained at initial presentation of PCP may predict early outcome and influence therapeutic approach, improving chances for survival.

Background Health-related quality of life (QoL) has become a crucial outcome in medical care. However, few studies have assessed physician knowledge of QoL and rate of physicians adopting QoL measures in clinical practice. The present study aimed at assessing the level of knowledge of QoL and the perceived importance of incorporating QoL assessment in clinical practice among physicians of a tertiary level academic hospital in Rome, Italy. Materials and methods A survey study performed through the distribution of a questionnaire assessing knowledge of QoL studies that used the SF-36 scale, participation in studies evaluating QoL as well as knowledge of journals publishing articles on QoL Physicians and residents at the hospital Policlinico Gemelli, Catholic University of Rome. Results Three-hundred nine physicians completed the questionnaire. Thirty-eight percent % reported knowing studies on QoL and using their results in clinical practice or for research purposes; 29% reported knowing the SF-36 questionnaire; 30% stated that at least one study assessing QoL had been conducted in their department. Fourty-six percent % stated that QoL must influence much or very much diagnostic choices and an even higher percentage reported that QoL must influence much or very much therapeutic and palliative strategies (70.8% and 91.3%, respectively). Reported barriers to the use of QoL measures in clinical practice were related to time constraints (8.7%) but also to doubts on methodological issues of QoL (30.7%). The large majority of physicians (94.3%) would have used more expensive drugs if these could improve QoL. Conclusions The present study shows that in a tertiary level academic italian hospital one third of the physicians, reported to know QoL measures and that more than 80% of them would like to use QoL in their daily clinical practice. Future studies are needed to identify the best strategies to implement the use of QoL measures in clinical practice.

The records of 49 consecutive AIDS patients with Kaposi's sarcoma were analysed retrospectively to assess the prognostic value of the four staging systems proposed for epidemic Kaposi's sarcoma. The classifications by Krigel and Mitsuyasu do not describe exactly the characteristics of the disease, and do not give enough information on survival. Our study confirms that CD4+ cell depletion, systemic symptoms and opportunistic infections at diagnosis are the major prognostic factors and influence survival to a great extent, as shown by Krown and Chachoua.

This study was intended to present evidence for the reliability and validity of an Italian version of the MOS-HIV Health Survey and to identify important disease-related factors associated with health-related quality of life (HRQoL) in people with nonadvanced HIV.In this cross-sectional study, HRQoL was measured using an Italian version of the MOS-HIV Health Survey questionnaire in 213 HIV-infected people without previous opportunistic infections or neoplasms attending an outpatient clinic in a university hospital. Distribution of scores, reliability, and validity were calculated, and presence and frequency of HIV-related symptoms were recorded and transformed into a score. The relation of HRQoL values to sociodemographic, epidemiologic, and clinical data was assessed.The level of internal consistency of the Italian version of the MOS-HIV Health Survey was high (Cronbach's alpha, 0.80-0.93), and items demonstrated acceptable discrimination across scales. At linear regression analysis, all domains of HRQoL correlated with symptom score (r2 range, 0.07-0.41), but only the pain and physical-functioning scores showed a significant correlation with CD4 cell count. A weighted sum of single domains of HRQoL, TOTQoL, is also strongly correlated with symptom score (r2 = 0.57; p.0001) but not with CD4 cell count (r2 = 0.01; p = .1). Using multivariate analysis, only symptom score (p.0001) and total number of daily pills (p = .03) showed significant association with HRQoL. The same results were observed when analysis was performed only on people with CD4 levels200/microl.This study presents the first evidence for the reliability and validity of a HRQoL instrument in Italian for people with HIV. Results also suggest a strong impact of symptoms on all measured dimensions of health status. The number of pills required to be taken daily is the only other significant factor associated with a lower HRQoL, whereas no relations were found with CD4 cell count or Karnofsky performance status values. To improve HRQoL in persons with nonadvanced HIV disease, symptom control could be a crucial element of medical treatment.

To determine the variability of genotypic human immunodeficiency virus (HIV) type 1 drug-resistance interpretation by available expert systems and its clinical implications, 261 subjects for whom a potent antiretroviral regimen was failing who were starting salvage therapy were evaluated. The association of the genotypic susceptibility score (GSS) of the salvage regimen, according to 11 interpretation systems, with HIV RNA outcomes for 6 months was examined. GSS was highly variable, as determined by the different interpretation systems, and showed independent correlation with changes from baseline HIV RNA levels at 6 months with 5 systems--Stanford hivdb, GuideLines 3.0, Retrogram 1.4, HIVresistanceWeb, and São Paulo University. Most GSSs predicted virologic response in regimens containing stavudine, lamivudine, efavirenz, or indinavir. Selected systems predicted response in regimens containing didanosine, abacavir, or nelfinavir, and no system predicted outcome of boosted protease inhibitors. GSSs predicted changes in HIV RNA levels better in adherent patients than in nonadherent individuals. Interpretation may be improved, and knowledge should be used uniformly throughout different expert systems.