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Pettoranello del Molise, Italy

Chinot O.L.,Aix - Marseille University | Wick W.,German Cancer Research Center | Mason W.,Princess Margaret Hospital | Henriksson R.,Regional Cancer Center | And 12 more authors.
New England Journal of Medicine

BACKGROUND: Standard therapy for newly diagnosed glioblastoma is radiotherapy plus temozolomide. In this phase 3 study, we evaluated the effect of the addition of bevacizumab to radiotherapy-temozolomide for the treatment of newly diagnosed glioblastoma. METHODS: We randomly assigned patients with supratentorial glioblastoma to receive intravenous bevacizumab (10 mg per kilogram of body weight every 2 weeks) or placebo, plus radiotherapy (2 Gy 5 days a week; maximum, 60 Gy) and oral temozolomide (75 mg per square meter of body-surface area per day) for 6 weeks. After a 28-day treatment break, maintenance bevacizumab (10 mg per kilogram intravenously every 2 weeks) or placebo, plus temozolomide (150 to 200 mg per square meter per day for 5 days), was continued for six 4-week cycles, followed by bevacizumab monotherapy (15 mg per kilogram intravenously every 3 weeks) or placebo until the disease progressed or unacceptable toxic effects developed. The coprimary end points were investigator-assessed progression-free survival and overall survival. RESULTS: A total of 458 patients were assigned to the bevacizumab group, and 463 patients to the placebo group. The median progression-free survival was longer in the bevacizumab group than in the placebo group (10.6 months vs. 6.2 months; stratified hazard ratio for progression or death, 0.64; 95% confidence interval [CI], 0.55 to 0.74; P<0.001). The benefit with respect to progression-free survival was observed across subgroups. Overall survival did not differ significantly between groups (stratified hazard ratio for death, 0.88; 95% CI, 0.76 to 1.02; P = 0.10). The respective overall survival rates with bevacizumab and placebo were 72.4% and 66.3% at 1 year (P = 0.049) and 33.9% and 30.1% at 2 years (P = 0.24). Baseline health-related quality of life and performance status were maintained longer in the bevacizumab group, and the glucocorticoid requirement was lower. More patients in the bevacizumab group than in the placebo group had grade 3 or higher adverse events (66.8% vs. 51.3%) and grade 3 or higher adverse events often associated with bevacizumab (32.5% vs. 15.8%). CONCLUSIONS: The addition of bevacizumab to radiotherapy-temozolomide did not improve survival in patients with glioblastoma. Improved progression-free survival and maintenance of baseline quality of life and performance status were observed with bevacizumab; however, the rate of adverse events was higher with bevacizumab than with placebo. Copyright © 2014 Massachusetts Medical Society. Source

Hicks G.E.,Delaware Rehabilitation Institute | Hicks G.E.,University of Delaware | Benvenuti F.,Azienda Unita Sanitaria Locale | Fiaschi V.,Unita Operativa Riabilitazione Funzionale Azienda Unita | And 6 more authors.
Clinical Journal of Pain

Objectives: To identify factors that were predictive of improved pain status among older adults with chronic back pain participating in the Adaptive Physical Activity (APA) program and to identify factors that were predictive of adherence to APA. Methods: An observational cohort study of 392 older adults (ages 50 to 88) with chronic back pain participating in APA for 12 months. APA was a community-based group exercise program given for 1-hour, twice weekly, in local gyms. Primary outcome measures were improved pain based on a global rating of change evaluation and adherence to the APA program (defined as participation in >75% of exercise sessions). Potential predictor variables were entered into multivariate logistic regression models to determine the most accurate set of variables for predicting improved pain and adherence. Results: Presence of depressive symptoms, poor self-rated health and adherence to APA were the best predictors of improved pain status, with adherence being the strongest predictor [odds ratio: 13.88 (95% confidence interval: 8.17, 23.59)]. Better physical function, longer pain duration, and positive rating of the trainer were all positively associated with adherence to APA; whereas poor self-rated health and further distance from the gym were inversely associated. Conclusions: Given that adherence to APA is the key predictor of improved back pain, future efforts should focus on strategies to improve adherence. Our data suggest that enhanced training of exercise trainers, development of separate classes for people with different functional levels, and use of psychosocial interventions to reduce health pessimism and depression may be potential targets for improving adherence. Copyright © 2012 by Lippincott Williams & Wilkins. Source

Gerra G.,Health and Human Development Section | Zaimovic A.,Azienda Unita Sanitaria Locale | Gerra M.L.,University of Parma | Ciccocioppo R.,University of Camerino | Cippitelli A.,University of Camerino
Recent Patents on CNS Drug Discovery

For centuries Cannabis sativa and cannabis extracts have been used in natural medicine. △9-tetrahydrocannabinol (THC) is the main active ingredient of Cannabis. THC seems to be responsible for most of the pharmacological and therapeutic actions of cannabis. In a few countries THC extracts (i.e. Sativex® ) or THC derivatives such as nabilone, and dronabinol are used in the clinic for the treatment of several pathological conditions like chemotherapy-induced nausea and vomiting, multiple sclerosis and glaucoma. On the other hand the severe side effects and the high abuse liability of these agents represent a serious limitation in their medical use. In addition, diversion in the use of these active ingredients for recreational purpose is a concern. Over recent years, alternative approaches using synthetic cannabinoid receptor agonists or agents acting as activators of the endocannabinoid systems are under scrutiny with the hope to develop more effective and safer clinical applications. Likely, in the near future few of these new molecules will be available for clinical use. The present article reviews recent study and patents with focus on the cannabinoid system as a target for the treatment of central nervous system disorders with emphasis on agonists. © 2010 Bentham Science Publishers Ltd. Source

Ferreri A.J.M.,San Raffaele Scientific Institute | Ciceri F.,San Raffaele Scientific Institute | Brandes A.A.,Azienda Unita Sanitaria Locale | Montanari M.,Ospedale di Ancona | And 9 more authors.

Objective: We report updated results at a median follow-up of 12 years of a phase II trial assessing first-line MATILDE chemotherapy and response-tailored radiotherapy in patients with primary CNS lymphomas (PCNSL). Methods: Forty-one HIV-negative patients (18-70 years; Eastern Cooperative Oncology Group performance status ≤3) with histologically confirmed PCNSL received 3 courses of MATILDE chemotherapy followed by whole-brain radiotherapy (WBRT). Chemotherapy activity was the primary endpoint. Results: Overall response rate was 76% (95% confidence interval [CI] 63%-89%) after chemotherapy and 83% (95% CI 71%-95%) after chemotherapy ± radiotherapy. At a median follow-up of 144 months (range 47-153), 31 patients experienced an event: relapse in 24, progressive disease in 3, and toxic death in 4, with a 5-year progression-free survival of 24% ± 8%. Two patients experienced a late relapse (100 and 101 months). Nine patients are alive and disease-free, 8 of whom are alive at >10 years, with a 5-year overall survival of 30% ± 7%. At 10 years from diagnosis, no patient showed chronic hematologic and nonhematologic toxicities, with a Mini-Mental State Examination score of ≥29 in all cases but one. Conclusions: At a median follow-up of 12 years, MATILDE regimen followed by WBRT confirmed the previously reported survival plateau, which further proves its long-lasting efficacy with acceptable neurologic deficits. Classification of evidence: This study provides Class IV evidence that in patients with PCNSL, MATILDE chemotherapy followed by response-tailored radiotherapy increases the probability of disease remission at 12 years. © 2014 American Academy of Neurology. Source

Manuguerra R.,University of Parma | Callegari S.,Azienda Unita Sanitaria Locale | Corradi D.,University of Parma
Journal of Cardiovascular Electrophysiology

AF in Inherited Structural Heart Diseases Inherited cardiac diseases inducing structural remodeling of the myocardium sometimes develop arrhythmias of various kinds. Among these rhythm disturbances, atrial fibrillation is well known to frequently worsen the prognosis of the primary disorder by increasing morbidity and mortality, especially because of a higher rate of heart failure. In this manuscript, we have reviewed the literature on the most important inherited structural cardiac diseases in whose clinical history atrial fibrillation may occur fairly often. © 2015 Wiley Periodicals, Inc. Source

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