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1.  Cost of HAART in Italy: multicentric evaluation and determinants from a large HIV outpatient cohort 
Background
As HIV infection turned into a chronic treatable disease, now ranking as one of the most costly in medicine, long-term sustainability of highly active antiretroviral treatment (HAART) expenses became a major issue, especially in countries with universal access to care. Identification of determinants of higher HAART costs may therefore help in controlling costs of care, while keeping high levels of retention in care and viral suppression.
Methods
With this aim, we enrolled a large multicentric sample of consecutive unselected human immunodeficiency virus (HIV) patients followed at five sites of care in Italy, and evaluated annual individual HAART costs in relation to a number of sociodemographic, clinical, and laboratory variables.
Results
We enrolled 2,044 patients, including 1,902 on HAART. Mean HAART costs were €9,377±€3,501 (range 782–29,852) per year, with remarkable site-based differences, possibly related to the different composition of local assisted populations. Percentages of patients on viral suppression were homogeneously high across all study sites. The factors identified by cross-validation were line of HAART, diagnosis of acquired immune deficiency syndrome, current CD4 T-cell count, and detectable HIV viremia >50 copies/mL. In the final multivariable model, HAART costs were independently directly associated with more advanced HAART line (P<0.001) and inversely correlated with current CD4 T-cell count (P=0.024). Site of care held independent prediction of higher costs, with marked control of expenses at sites 2 (P=0.001) and 5 (P<0.001).
Conclusion
Higher costs of HAART were strongly associated with previous treatment failures, detectable HIV viremia, and lower CD4 T-cell count at the time of evaluation, with no correlation at all with sex, age, hepatitis C virus coinfection, and nadir CD4 T-cell counts. Newer drugs, which are typically those associated with high prices, at the time of the analysis were still prevalently prescribed to rescue and maintain viral suppression in patients with more complex treatment history. Further analyses of the contribution of the single drug/regimen to the estimated cost are warranted.
doi:10.2147/CEOR.S69183
PMCID: PMC4278727  PMID: 25565872
highly active antiretroviral treatment; human immunodeficiency virus; costs; treatment failures; viremia; current CD4 count
2.  Small Colony Variant of Methicillin-Resistant Staphylococcus pseudintermedius ST71 Presenting as a Sticky Phenotype 
Journal of Clinical Microbiology  2014;52(4):1225-1227.
We first observed the phenomenon of small colony variants (SCVs) in a Staphylococcus pseudintermedius sequence type 71 (ST71) strain, isolated from a non-pet owner. Although we found that small-sized colonies share main features with Staphylococcus aureus SCVs, they nevertheless show a novel, particular, and sticky phenotype, whose expression was extremely stable, even after subcultivation.
doi:10.1128/JCM.02861-13
PMCID: PMC3993511  PMID: 24452163
3.  Five-Year Retrospective Italian Multicenter Study of Visceral Leishmaniasis Treatment 
The treatment of visceral leishmaniasis (VL) is poorly standardized in Italy in spite of the existing evidence. All consecutive patients with VL admitted at 15 Italian centers as inpatients or outpatients between January 2004 and December 2008 were retrospectively considered; outcome data at 1 year after treatment were obtained for all but 1 patient. Demographic characteristics, underlying diseases, diagnostic procedures, treatment regimens and outcomes, as well as side effects were recorded. A confirmed diagnosis of VL was reported for 166 patients: 120 (72.3%) immunocompetent, 21 (12.6%) patients with immune deficiencies other than HIV infection, and 25 (15.1%) coinfected with HIV. Liposomal amphotericin B (L-AmB) was the drug almost universally used for treatment, administered to 153 (92.2%) patients. Thirty-seven different regimens, including L-AmB were used. The mean doses were 29.4 ± 7.9 mg/kg in immunocompetent patients, 32.9 ± 8.6 mg/kg in patients with non-HIV-related immunodeficiencies, and 40.8 ± 6.7 mg/kg in HIV-infected patients (P < 0.001). The mean numbers of infusion days were 7.8 ± 3.1 in immunocompetent patients, 9.6 ± 3.9 in non-HIV-immunodeficient patients, and 12.0 ± 3.4 in HIV-infected patients (P < 0.001). Mild and reversible adverse events were observed in 12.2% of cases. Responsive patients were 154 (93.3%). Successes were 98.4% among immunocompetent patients, 90.5% among non-HIV-immunodeficient patients, and 72.0% among HIV-infected patients. Among predictors of primary response to treatment, HIV infection and age held independent associations in the final multivariate models, whereas the doses and duration of L-AmB treatment were not significantly associated. Longer treatments and higher doses of L-AmB were not able to significantly modify treatment outcomes either in the immunocompetent or in the immunocompromised population.
doi:10.1128/AAC.00840-13
PMCID: PMC3910784  PMID: 24189252
4.  Surgical wound infection by mannitol-nonfermenting Staphylococcus aureus after lumbar microdiscectomy 
Purulent infection of a surgical wound developed after discectomy, and a mannitol-nonfermenting Staphylococcus aureus isolate was cultivated as the etiologic agent. Nonfermenting S. aureus strains are exceedingly rare and may be erroneously mistaken and dismissed as contaminants. This report then emphasizes that pure and massive cultures must be carefully evaluated, even if preliminary examination does not suggest a pathogenic organism. Also, although mannitol-negative, the studied strain was correctly detected as S. aureus by both the-FISH test (AdvanDx, USA) and the Liofilchem ‘Chromatic Staph aureus’, highlighting that additional diagnostic methods may support recognition of uncommon, nonfermenting S. aureus strains in the daily practice.
PMCID: PMC4069970  PMID: 24966984
Mannitol; Staphylococcus aureus; surgical wound
6.  Methicillin-Resistant Staphylococcus pseudintermedius Infection in a Bone Marrow Transplant Recipient 
Journal of Clinical Microbiology  2013;51(5):1636-1638.
Staphylococcus pseudintermedius is a veterinary pathogen that has seldom been described as an agent of human disease. Features of this probably underreported coagulase-positive Staphylococcus species are depicted here through the description of a graft-versus-host disease-related wound infection caused by a multidrug-resistant strain.
doi:10.1128/JCM.03310-12
PMCID: PMC3647946  PMID: 23486715
7.  Preliminary Evaluation of the Safety and Efficacy of Standard Intravenous Immunoglobulins in Pregnant Women with Primary Cytomegalovirus Infection 
Clinical and Vaccine Immunology : CVI  2012;19(12):1991-1993.
Hyperimmune globulins were reported to prevent and treat fetal cytomegalovirus (CMV) infection during pregnancy. Here, we report that infusions of standard human intravenous immunoglobulin significantly increase CMV IgG titers and avidity indexes in pregnant women, paving the way to their use for passive transfer of maternal CMV humoral immunity to fetuses. Preliminary data on perinatal outcomes of the first 67 newborns are encouraging.
doi:10.1128/CVI.00509-12
PMCID: PMC3535874  PMID: 23100477
8.  Post-herpetic neuralgia 
Background
In spite of the large body of evidence available in the literature, definition and treatment of Post-Herpetic Neuralgia (PHN) are still lacking a consistent and universally recognized standardization. Furthermore, many issues concerning diagnosis, prediction and prevention of PHN need to be clarified in view of recent contributions.
Objectives
To assess whether PHN may be better defined, predicted, treated and prevented in light of recent data, and whether available alternative or adjunctive therapies may improve pain relief in treatment recalcitrant PHN.
Methods
Systematic reviews, meta-analyses, randomized controlled trials, cohort studies and protocols were searched; the search sources included PubMed, Cochrane Library, NICE, and DARE. More than 130 papers were selected and evaluated.
Results
Diagnosis of PHN is essentially clinical, but it can be improved by resorting to the many tools available, including some practical and accessible questionnaires. Prediction of PHN can be now much more accurate, taking into consideration a few well validated clinical and anamnestic variables. Treatment of PHN is presently based on a well characterized array of drugs and drug associations, including, among others, tricyclic antidepressants, gabapentinoids, opioids and many topical formulations. It is still unsatisfactory, however, in a substantial proportion of patients, especially those with many comorbidities and intense pain at herpes zoster (HZ) presentation, so that this frequent complication of HZ still strongly impacts on the quality of life of affected patients.
Conclusion
Further efforts are needed to improve the management of PHN. Potentially relevant interventions may include early antiviral therapy of acute HZ, prevention of HZ by adult vaccination, as well as new therapeutic approaches for patients experiencing PHN.
doi:10.2147/IJGM.S10371
PMCID: PMC3479946  PMID: 23109810
pain relief; PHN treatment; PHN predictors; PHN prevention
9.  Successful salvage therapy with Daptomycin for osteomyelitis caused by methicillin-resistant Staphylococcus aureus in a renal transplant recipient with Fabry-Anderson disease 
Daptomycin is licensed in adults for the management of Staphylococcus aureus methicillin-resistant infections, including bone and skin complicated infections. We describe for the first time its use in a renal transplant recipient for Fabry-Anderson Disease with right heel osteomyelitis. The patient was unresponsive to first-line Teicoplanin and second-line Tigecycline, whereas he was successfully treated with third-line Daptomycin monotherapy at 4 mg/Kg/qd for 4 weeks. Local debridement was performed in advance of each line of treatment.
doi:10.1186/1476-0711-11-6
PMCID: PMC3324387  PMID: 22404900
Methicillin-resistant Staphylococcus aureus; Osteomyelitis; Daptomycin; Salvage therapy; Antibiotic therapy
10.  Acupuncture for the treatment of severe acute pain in Herpes Zoster: results of a nested, open-label, randomized trial in the VZV Pain Study 
Background
Data on the potential efficacy of acupuncture (AC) in controlling intense or very intense pain in patients with Herpes Zoster (HZ) has not been so far adequately assessed in comparison with standard pharmacological treatment (ST) by a controlled trial design.
Methods
Within the VZV Pescara study, pain was assessed in HZ patients on a Visual Analogue Scale (VAS) and by the McGill Pain Questionnaire (MPQ) both at the beginning and at the end of treatment. Response rates, mean changes in pain intensity, differences in total pain burden with an area-under-the-curve (AUC) method over a 1-year follow-up and differences in the incidence of Post-Herpetic Neuralgia (PHN) were evaluated.
Results
One hundred and two patients were randomized to receive either AC (n = 52) or ST (n = 50) for 4 weeks. Groups were comparable regarding age, sex, pain intensity at presentation and missed antiviral prescription. Both interventions were largely effective. No significant differences were observed in response rates (81.6% vs 89.2%, p = 0.8), mean reduction of VAS (4.1 +/- 2.3 vs 4.9 +/- 1.9, p = 0.12) and MPQ scores (1.3 +/- 0.9 vs 1.3 +/- 0.9, p = 0.9), incidence of PHN after 3 months (48.4% vs 46.8%, p = 0.5), and mean AUC during follow-up (199 +/- 136 vs 173 +/- 141, p = 0.4). No serious treatment-related adverse event was observed in both groups.
Conclusions
This controlled and randomized trial provides the first evidence of a potential role of AC for the treatment of acute herpetic pain.
Trial registration
ChiCTR-TRC-10001146.
doi:10.1186/1472-6882-11-46
PMCID: PMC3125389  PMID: 21639941
11.  Tinea incognito Caused by Microsporum gypseum in a Patient with Advanced HIV Infection: A Case Report 
Case Reports in Dermatology  2011;3(1):55-59.
The prevalence and the clinical relevance of dermatophytoses in HIV-infected patients are poorly documented, particularly for those caused by tinea incognito. Here, we report a case of widespread facial tinea incognito occurring in an Italian patient with advanced HIV infection, showing both skin and brain lesions. Second-line treatment with liposomal amphotericin B and cotrimoxazole, administered after a microbiological characterization of the skin scrapings, led to complete clearance of all lesions.
doi:10.1159/000326055
PMCID: PMC3073754  PMID: 21487462
HIV infection; Tinea incognito; Microsporum gypseum
12.  Predictors of pain intensity and persistence in a prospective Italian cohort of patients with herpes zoster: relevance of smoking, trauma and antiviral therapy 
BMC Medicine  2010;8:58.
Background
Herpes zoster (HZ) is a common disease, characterized by rash-associated localized pain. Its main complication, post-herpetic neuralgia (PHN), is difficult to treat and may last for months to years in the wake of rash resolution. Uncertainties remain as to the knowledge of predictors of HZ-related pain, including the role of antiviral therapy in preventing PHN in ordinary clinical practice. This prospective cohort study was aimed at investigating pain intensity at HZ presentation and its correlates, as well as the incidence of PHN and its predictors.
Methods
Patients diagnosed with HZ were consecutively enrolled by a network of Italian General Practitioners and Hospital Units in the health district of Pescara, Italy, over two years. Uncertain cases were referred for microbiological investigation. Data were collected through electronic case report form (e-CRFs) at enrolment and at 1, 3, 6 and 12 months after enrolment. Pain intensity was coded on a five-degree semi-quantitative scale at each time point. PHN was defined as pain of any intensity during follow-up and quantified using an area-under-the-curve (AUC) method.
Results
Four hundred and forty-one patients composed the final sample. Mean age was 58.1 years (SD = 20.4 years); 43.5% of patients were males; 7.9% did not receive prescription of antivirals. Intense/very intense pain at presentation was reported by 25.2% of patients and was significantly associated with female gender, older age, cigarette smoking, trauma and/or surgery at HZ site (logistic regression). PHN was diagnosed in 51.2% of patients at one month and in 30.0% of patients at three months. PHN was significantly associated with pain intensity at presentation, age, smoking, trauma and missed antiviral prescription (generalized estimating equations model). The same factors were also independent predictors of the overall pain burden as described by the AUC method (linear regression).
Conclusions
Smoking, traumas and surgery at the HZ site emerged as new predictors of both HZ-related pain intensity and persistence, opening new perspectives in the prevention of HZ-related pain. An independent line of evidence was provided for the efficacy of antiviral therapy in preventing PHN and reducing total pain burden.
doi:10.1186/1741-7015-8-58
PMCID: PMC2964549  PMID: 20937086
13.  Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature 
Introduction
Selection of the K103N mutation is associated with moderately reduced in vitro fitness of HIV. Strains bearing K103N in vivo tend to persist, even in the absence of additional drug pressure, as minority quasispecies, often undetectable in genotyping resistance testing assays, performed at standard conditions. Here, we report on the rapid and long lasting selection of a K103N bearing strain as the dominant quasispecies after very short exposure to efavirenz in vivo.
Case presentation
A 55-year-old Caucasian man was switched to efavirenz, zidovudine and lamivudine in February 2003, while on viral suppression in his first-line highly active anti-retroviral treatment regimen. One month later, he reported inconsistent adherence and his viremia level was 5700 c/mL. He did not attend further checkups until September 2005, when his viral load was 181,000 c/mL. The patient reported interrupting his medications approximately three weeks after simplification. The genotyping resistance testing assay was performed both on HIV RNA and HIV DNA from plasma, yielding an identical pattern with the isolate presence of the K103N mutation in the prevalent strain.
Conclusion
Persistence of the K103N mutation as a majority quasispecies may ensue after a very short exposure to efavirenz. Our case would therefore suggest that the presence of the K103N mutation should always be ruled out by genotyping resistance testing assays, even after minimal exposures to efavirenz.
doi:10.4076/1752-1947-3-9132
PMCID: PMC2827172  PMID: 21092074

Results 1-13 (13)