41 research outputs found
Cohort profile: The Observational cohort for the study of DOlutegravir in Antiretroviral Combination REgimens (ODOACRE)
The Observational cohort for the study of DOlutegravir in Antiretroviral Combination REgimens (ODOACRE) cohort was established in Italy in 2016 to evaluate the overall efficacy and tolerability of dolutegravir (DTG)-based antiretroviral (ARV) regimens in clinical practice
Treatment of Low-Blast Count AML using Hypomethylating Agents
In 2002, the WHO classification reduced the proportion of blasts in the bone marrow (BM) necessary for the diagnosis of acute myeloid leukemia (AML) from 30% to 20%, eliminating the RAEB-t subtype of myelodysplastic syndromes (MDS). However, this AML subtype, defined as low-blast count AML (LBC-AML, with 20-30% BM-blasts) is characterized by peculiar features, as increased frequency in elderly individuals and after cytotoxic treatment for a different primary disease (therapy-related), poor-risk cytogenetics, lower white blood cell counts, and less frequent mutations of NPM1 and FLT3 genes. The clinical course of this entity is often similar to MDS with 10-19% BM-blasts. The hypomethylating agents azacitidine and decitabine have been shown to induce responses and prolong survival both in MDS and LBC-AML. The role of these agents has been also demonstrated in AML with >30% BM-blasts, particularly in patients with poor-risk cytogenetics and in AML with myelodysplasia related changes. Most recent studies are evaluating strategies to improve outcome, including combinations of hypomethylating agents with immune-response checkpoint inhibitors, which have a role in cancer immune surveillance. Efforts are also ongoing to identify mutations which may predict response and survival in these patients
Clinical features and comorbidity pattern of HCV infected migrants compared to native patients in care in Italy: A real-life evaluation of the PITER cohort
Background: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. Methods: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. Results: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both groups, whereas genotype 4 was more prevalent in migrants (p < 0.05). Liver disease severity and sustained virologic response (SVR) were similar. A higher prevalence of comorbidities was reported for natives compared to migrants (p < 0.05). Liver disease progression cofactors (HBsAg, HIV coinfection, alcohol abuse, potential metabolic syndrome) were present in 39.1% and 47.1% (p > 0.05) of migrants and natives who eradicated HCV, respectively. Conclusion: Compared to natives, HCV-infected migrants in care have different demographics, HCV genotypes, viral coinfections and comorbidities and similar disease severity, SVR and cofactors for disease progression after HCV eradication. A periodic clinical assessment after HCV eradication in Italians and migrants with cofactors for disease progression is warranted
Economic consequences of investing in anti-HCV antiviral treatment from the Italian NHS perspective : a real-world-based analysis of PITER data
OBJECTIVE:
We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy.
METHODS:
A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered.
RESULTS:
The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal âŹ25 million, âŹ15 million, and âŹ9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were âŹ50.13 and âŹ55.50 million for 1000 patients treated in 2016 and 2017, respectively.
CONCLUSIONS:
This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV
L'Italia come modello per l'Europa e per il mondo nelle politiche sanitarie per il trattamento dell'epatite cronica da HCV
The World Health Organization foresees the
elimination of HCV infection by 2030. In light of this and the curre
nt, nearly worldwide, restriction in direct-acting agents
(DAA) accessibility due to their high price, we aimed to evaluate
the cost-effectiveness of two alternative DAA treatment
policies: Policy 1 (universal): treat all patients, regardless of the fibrosis stage; Policy 2 (prioritized): treat only priori
tized
patients and delay treatment of the
remaining patients until reaching stage F3. T
he model was based on patientâs data
from the PITER cohort. We demonstrated that extending HC
V treatment of patients in any fibrosis stage improves health
outcomes and is cost-effective
Quantification of the HIV-1 total reservoir in the peripheral blood of naĂŻve and treated patients by a standardised method derived from a commercial HIV-1 RNA quantification assay.
HIV-1 DNA can persist in host cells, establishing a latent reservoir. This study was aimed to develop an extraction and amplification protocol for HIV-1 DNA quantification by modifying a quantitative commercial assay. HIV-1 DNA was extracted on an Abbott m2000sp instrument, using an open-mode protocol. Two calibrators, spiked with a plasmid containing HIV-1 genome (103 and 105 cps/mL), were extracted and amplified to generate a master calibration curve. Precision, accuracy, linear dynamic range, limit of quantification (LOQ) and limit of detection (LOD) were determined. A cohort of patients, naĂŻve or chronically infected, was analysed. Calibration curve was obtained from 42 replicates of standards (stds); precision was calculated (coefficients of variability [CVs] below 10%); accuracy was higher than 90%. Linearity covered the entire range tested (10-104 copies per reaction), and LOD (95%) was 12 copies per reaction. HIV-1 DNA was significantly higher (p < 0.0001) in drug-naĂŻve (62) than in chronically treated patients (50), and proviral loads correlated with lymphocytes (p = 0.0002) and CD4+ (p < 0.0001) counts only in naĂŻve patients. Both groups displayed a significant inverse correlation between CD4+ nadir and proviral loads. A significant correlation (p < 0.0001) between viraemia and HIV-1 reservoir was disclosed. No significant difference was obtained from the comparison between proviral loads on whole blood and peripheral blood mononuclear cells (PBMCs) from the same patient. The novelty of our approach relies on the selection of appropriate reference standard extracted and amplified as clinical specimens avoiding any underestimation of the reservoir. Results confirm HIV-1 DNA as a marker of disease progression, supporting the relationship between the width of latent reservoir and the immunological status of the patient
Candidemia in Internal Medicine: Facing the New Challenge
Candidemia is an alarming problem in critically ill patients including those admitted in Internal Medicine Wards (IMWs). Here, we analyzed all cases of candidemia in adult patients hospitalized over nine years (2010â2018) in IMWs of a 980-bedded University Hospital of Ancona, Italy. During the study period, 218/505 (43%) episodes of candidemia occurred in IMWs patients. The cumulative incidence was 2.5/1000 hospital admission and increased significantly over time (p = 0.013). Patients were predominantly male, with a median age of 68Â years. Cardiovascular diseases and solid tumors were the most frequent comorbidities. Candida albicans accounted for 51% of the cases, followed by C. parapsilosis (25%), C. tropicalis (9%) and C. glabrata (7%). Thirty-day mortality was 28% and did not increased significantly over time. By multivariate logistic regression analysis, the presence of neutropenia (OR 7.247 [CI95% 1,368â38,400; p = 0.020]), pneumonia (OR 2.323 [CI95% 1,105â4,884; p = 0.026]), and being infected with C. albicans (OR 2.642 [95% CI 1,223â5,708; p = 0.013) emerged as independent predictors of mortality. The type of antifungal therapy did not influence the outcome. Overall, these data indicate that patients admitted to IMWs are increasingly at higher risk of developing candidemia. Mortality rate remains high and significantly associated with both microbiologic- and host-related factors
Characterisation of candidemia in patients with recent surgery: A 7-year experience
Candidemia can complicate major surgical procedures. However, literature data are scanty on this topic. In this study, we evaluated the epidemiology, clinical and microbiologic characteristics and outcome of candidemia in adult patients with recent surgery hospitalised in a single University Hospital in Central Italy from 2010 to 2016. Of the 304 episodes of candidemia, 160 (53%) occurred in surgical patients (SPs) while the remaining 144 (47%) in patients without history of recent surgery (non-SPs). Although either underlying chronic comorbidities (ie haematological malignancies, neurological and gastrointestinal diseases) or acute complications (ie pneumonia and septic shock) were less likely to occur in SPs than in non-SPs, 30-day mortality did not differ between groups being 38% and 42%, respectively. The specific risk factors significantly more common in SPs who died within 30 days were as follows: male gender, older age, being hospitalised in ICU rather than in other wards, having a higher Charlson's score, undergoing previous invasive procedures, haemodialysis, the presence of pneumonia, septic shock, acute kidney failure and the type of surgery. In particular, either gastrointestinal or cardiovascular surgeries were characterised by the highest mortality rates. Multivariate analysis showed that the occurrence of septic shock (HR 10.3131 [CI95% 1.176-90.466; P = .035] and ICU stay (HR 2.016 [CI95% 1.178-3.448; P = .011] was independently associated with higher mortality in SPs. Overall, these data show that candidemia in SPs is characterised by significant mortality and distinctive features
Therapy with direct-acting antiviral agents in transplanted patients with HCV recurrence: a retrospective analysis
The recurrence of HCVinfection after liver transplantation was the main cause of mortality and loss of graft in transplanted patients until the use of direct-acting antivirals (DAAs).We performed amonocentric retrospective study from November 2014 to September 2017 at âOspedali Riunitiâ, Ancona, Italy, to evaluate the outcome and tolerability of DAAs after liver transplantation. In total, 55 patients with HCV recurrence after liver transplantation treated with DAAs were included. The most frequent genotype was genotype 1a (36%), followed by genotype 3a (27%). The majority of the patients presented a mild or moderate hepatic fibrosis (METAVIR score of F0 - F1 in 20% and F2 in 27%). The patients received sofosbuvir + daclatasvir, sofosbuvir + ribavirin, sofosbuvir + simeprevir, sofosbuvir + ledipasvir, and sofosbuvir + velpatasvir in 54%, 18%, 13%, 13%, and 2% of the cases, respectively, for 12 or 24 weeks. The SVR 12 rate was 89% overall, without a statistically significant relationship with genotypes, fibrosis stage, and therapy. Moreover, 52% of the patients modified the dosage of tacrolimus in the first three months of therapy with DAAs, without statistical significance compared to the group that not changed tacrolimus dosage. The most frequent adverse events were anemia associated with ribavirin. IFN-free treatment with DAAs is highly effective for HCV relapse after liver transplantation and it showed high tolerability in our patients