Long-term effect of HCV eradication in patients with mixed cryoglobulinemia: A prospective, controlled, open-label, cohort study

Limited data are available about the efficacy of antiviral treatment in hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC), especially concerning the long-term effects of HCV eradication. The aim of this study was to evaluate the influence of MC on the virological response and the long-term effects of viral eradication on MC. We prospectively enrolled 424 HCV+ patients belonging to the following groups: MCS-HCV (121 patients with symptomatic MC); MC-HCV (132 patients with asymptomatic MC); HCV group (158 patients without MC). Peg-IFN+RBV treatment was administered according to standard protocols. Post-treatment follow-up ranged from 35 to 124 months (mean: 92.5 months). A significant difference was observed in the rate of sustained virological response (SVR) between HCV and both MC-HCV (p=0.009) and MC-HCV+MCS-HCV (p=0.014) groups. Multivariate logistic regression analysis identified cryoglobulinemia as an independent prognostic factor of non-response. The clinical-immunological response in MCS-HCV correlated with the virological one. All patients with SVR also experienced a sustained clinical response, either complete or partial. In the majority of SVR patients all MCS symptoms persistently disappeared (36 patients, 57%); in only 2 (3%) did definite MCS persist. All virological non-responders were also clinical non-responders, in spite of a transient improvement in some cases. No evolution to lymphoma was observed. For the first time we have evaluated both the effects of IFN-based therapy on HCV patients with or without MC, and with or without symptoms, and the long-term effects of viral eradication on MC. MC was shown to be a negative prognostic factor of virological response. HCV clearance led to persistent resolution or improvement of MC syndrome, strongly suggesting the need for a next generation of highly effective antiviral drugs

Phase II Randomized Study of Vandetanib Plus Gemcitabine or Gemcitabine Plus Placebo as First-Line Treatment of Advanced Non–Small-Cell Lung Cancer in Elderly Patients

Introduction:The aim of the present study was to evaluate the efficacy and tolerability of vandetanib plus gemcitabine (V/G) compared with gemcitabine alone in elderly patients with untreated advanced non–small-cell lung cancer.Methods:This was a phase II, randomized, double-blind study. A total of 124 elderly patients (mean age, 75 yr; age range, 70–84 yr; 73% men) received V/G (n = 61) or placebo plus gemcitabine (n = 63). Progression-free survival (PFS) was the primary endpoint. Secondary endpoints were overall survival, objective response rate, duration of response, disease control rate, time to deterioration of performance status, and safety outcomes.Results:PFS was significantly prolonged with V/G (median, 183 days; 95% confidence interval, 116–214) compared with placebo plus gemcitabine (median, 169 days; 95% confidence interval, 95–194; p = 0.047). No statistically significant differences between arms were observed in all secondary endpoints, including overall survival. The addition of vandetanib to gemcitabine was well tolerated. The rate of patients with ≥1 treatment-related adverse event was comparable in the two arms, pyrexia, dyspnea, and neutropenia being the most common adverse events.Conclusions:V/G combination was associated with a statistically significant prolongation of PFS compared with gemcitabine alone in untreated elderly patients with advanced non–small-cell lung cancer, with an acceptable safety profile

Cytopenias during treatment of HIV–HCV-coinfection with pegylated interferon and ribavirin: safety analysis of the OPERA study

Background: Until recently, recommendations for HCV treatment in HIV-coinfected patients have been combination therapy with pegylated interferon (PEG-IFN) and ribavirin (RBV). However, this treatment is often accompanied with cytopenias which lead to drug-dose reduction/discontinuation, therefore influencing sustained virological response (SVR). This study aimed at evaluating incidence and predictors of cytopenias and to define their impact on SVR in Italian HIV–HCV-coinfected patients undergoing PEG-IFN/RBV treatment. Methods: OPERA was a multicentric, observational study conducted in 98 Italian centres. Patients with HIV–HCV coinfection were administered with PEG-IFN/RBV combination treatment for 48 weeks. Incidence and time of onset of cytopenias and multiple bone marrow toxicity (mBMT) was monitored. Logistic regression analysis assessed factors associated with SVR, anaemia, neutropenia, thrombocytopenia and mBMT. Results: Between 2005 and 2011, 1,523 patients were enrolled. Anaemia (haemoglobin <10 g/dl) occurred in 197 (12.9%) patients and a haemoglobin drop ≥3 g/dl was recorded in 796 (52.3%). Anaemia did not impact on SVR, its rate being 42.1% and 38.1%, respectively, in patients with and without anaemia (P=0.31). Therapy discontinuation due to anaemia occurred in 47 patients (3.1%). Neutropenia (<1,000 neutrophils/mm3) occurred in 652 (42.8%) patients, and SVR was higher (P<0.001) for patients with neutropenia (44.8%) compared to without neutropenia (34%). Patients developing neutropenia did not have an increased risk of developing infections. Thrombocytopenia (<100,000 platelets/mm3) occurred in 595 (39.1%) patients, SVR was not influenced by it (38.2% versus 38.9% in patients with and without thrombocytopenia, respectively; P=0.79), and 16 patients (1.1%) discontinued therapy due to it. Cirrhosis was found in 148/734 evaluated patients (20.2%) and was significantly associated with thrombocytopenia (P<0.0001). mBMT was found in 417 patients (27.4%). Conclusions: Cytopenias are frequent side effects of PEG-IFN/RBV combination therapy in HIV–HCV-coinfected patients. However, SVR is not negatively affected by their presence, nor is there an increased risk of infections in patients developing neutropenia. Several predicting factors for the onset of cytopenias have been unravelled, which will help to identify early those patients at high risk of developing cytopenia

Effectiveness of budesonide MMX (Cortiment) for the treatment of mild-to-moderate active ulcerative colitis: study protocol for a prospective multicentre observational cohort study

INTRODUCTION: A study has been developed to assess the use and effectiveness of budesonide MMX for mild-to-moderate active ulcerative colitis (UC) in routine clinical practice. METHODS AND ANALYSIS: A prospective, multicentre, observational, cohort study of 300 patients prescribed budesonide MMX for the treatment of mild-to-moderate active UC will be conducted in Europe, Israel and Canada. Patients will be treated with budesonide MMX9 mg daily for induction of remission for ≤8 weeks. Data on effectiveness, including patient-reported outcomes, tolerability and use will be recorded at the end of treatment and at ≥2 weeks after. The primary outcome (improvement ≥3 point in the clinical subscores of the UC Disease Activity Index score at the end of treatment) will be compared in: patients who receive budesonide MMX added to mesalazine >2 weeks after increased/optimised mesalazine dose for the treatment of flare (late add-on); patients who receive budesonide MMX added to mesalazine ≤2 weeks since mesalazine increased/optimised for the treatment of flare, or without mesalazine dose modification (early add-on); and patients who receive budesonide MMX as monotherapy for the treatment of flare (mono). Propensity scoring will be used to minimise bias and confounding inherent in observational studies. ETHICS AND DISSEMINATION: First ethical approval: Ethikkommission der Ärztekammer Hamburg (12/22/2015). The results will be published in full. DISCUSSION: Completion of primary data collection is expected in December 2017. Our results will provide further evidence on the effectiveness of budesonide MMX to support clinicians in their daily practice and inform therapeutic guidelines. TRIAL REGISTRATION NUMBER: NCT02586259

Populatieanalyse Groninger Paard

We prijzen Nederlandse paardenrassen zoals het Groninger paard niet alleen omdat ze onderdeel van ons cultuurhistorisch erfgoed zijn maar ook vanwege hun veelzijdigheid en betrouwbare karakter. Helaas is de populatie klein. Dan is een goed doordacht fokbeleid nodig voor het behoud van genetische diversiteit en een gezonde populati

Validation of a stopping rule at week 12 using HBsAg and HBV DNA for HBeAg-negative patients treated with peginterferon alfa-2a

Background & Aims: It was recently demonstrated that none of the hepatitis B e antigen (HBeAg)-negative patients without any serum hepatitis B surface antigen (HBsAg) decline and with <2 log hepatitis B virus (HBV) DNA decline at week 12 of a 48-week peginterferon alfa-2a (PEG-IFN) treatment course achieved a sustained response (SR). We aimed at validating this stopping rule in two independent trials