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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 | Year: 2014

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.


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 | Year: 2010

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.


PubMed | University of L'Aquila, Instituto Oncologico Veneto IOV IRCCS and Azienda Unita Sanitaria Locale
Type: | Journal: Preventive medicine reports | Year: 2017

Offering self-sampling devices improves participation of under-screened women. We evaluated participation in routine screening following the self-sampling intervention in two organized population-based screening programmes located in North-East Italy. Data on participation at 3-years-interval after a randomized clinical trial assessing the response to two strategies offering self-samplers (sent at home or offered free at local pharmacy) with a control action (sending reminders for a cervical specimen taken at the clinic) in 30-64yr-old women non-respondent to the regular call-recall invitation were analyzed. Up to April 2016, 2300 women out of the 2995 recruited in the trial in 2011 were re-invited to perform a screening test at clinic; overall, 698 women adhered. Participation was similar in the three arms (29-32%), and highest (47-68%) among those who participated in the previous round. Over the two rounds, 44.6%, 32.3% and 30.3% women had at least one test in the self-sampling at home, self-sampling at pharmacy and test at the clinic arms, respectively. Our data indicate that the beneficial effect of offering self-sampling devices to nonparticipating women is maintained over time. Self-samplers are useful to increase overall coverage; their sporadic use does not seem to increase the proportion of women regularly repeating the test.


Benvenuti F.,Azienda Unita Sanitaria Locale 11 | Stuart M.,University of Maryland Baltimore County | Cappena V.,Azienda Unita Sanitaria Locale 11 | Gabella S.,Azienda Unita Sanitaria Locale 11 | And 5 more authors.
Neurorehabilitation and Neural Repair | Year: 2014

Background. Arm paresis remains a major impairment after stroke despite the best conventional rehabilitation. Randomized, controlled trials of intensive exercise programs have demonstrated improvements in arm function for patients with chronic stroke. However, the gains achieved have been relatively modest for the large investments in patient and therapist time. Objective. To evaluate the safety, acceptance, adherence, and effectiveness of a community-based exercise program for upper limb paresis in patients with chronic stroke and the effects of telerehabilitation monitoring in kiosks distributed through the community. Methods. Longitudinal cohort with geographic control group. The experimental group received devices needed for a home exercise program based on the Carr and Shepherd "Motor Learning Program" and were instructed to practice the exercises at least twice a week at the kiosk and at least 3 more days a week at home. The control group received usual care. Results. Compared with the control group, patients in the experimental group demonstrated significant gains in arm function as measured by the Wolf Motor Function Test, 9-Hole Peg Test, Motricity Index, and Nottingham Extended Activities of Daily Living Questionnaire. The intervention received high satisfaction ratings and produced no adverse events. Only 30% of the subjects attended kiosks regularly. Outcomes for this group did not differ significantly from those who only practiced at home. Conclusions. Home- and community-based exercise for arm paresis is safe and effective. Telerehabilitation interventions will need additional enhancements to improve effectiveness. The optimal upper extremity exercise prescription poststroke remains to be established. © The Author(s) 2014.


PubMed | CEDAF, Azienda Unita Sanitaria Locale, Hygeia Diagnostic and Therapeutic Center, Singularlogic and 3 more.
Type: Journal Article | Journal: International journal of geriatric psychiatry | Year: 2016

The aim of this paper was to assess the efficacy of process-based cognitive training (pb-CT) combined with reminiscence therapy (RT) in patients with mild Alzheimers disease (mAD) and mild cognitive impairment (MCI) and in healthy elderly (HE) subjects.This multicenter, randomized, controlled trial involved 348 participants with mAD, MCI, and HE from four European countries. Participants were randomly assigned to two arms of a crossover design: those in arm A underwent 3 months of computerized pb-CT for memory and executive functions combined with RT and 3 months of rest; those in arm B underwent the reverse. The primary outcome was the effect of the training on memory and executive functions performance. The secondary outcome was the effect of the training on functional abilities in mAD assessed with the instrumental activities of daily living.We found a significant effect of the training for memory in all three groups on delayed recall of the Rey Auditory Verbal Learning Test and for executive functions in HE on the phonological fluency test. MCI and HE participants maintained these effects at follow-up. MCI and mAD participants also showed a significant effect of the training on the Mini-mental state examination scale. Participants with mAD showed more stable instrumental activities of daily living during the training versus the rest period.Our results corroborate the positive effect of pb-CT and its maintenance primarily on memory in HE and MCI participants that did not seem to be potentiated by RT. Moreover, our results are very promising for the mAD participants.


Mossello E.,University of Florence | Pieraccioli M.,University of Florence | Nesti N.,University of Florence | Bulgaresi M.,University of Florence | And 11 more authors.
JAMA Internal Medicine | Year: 2015

IMPORTANCE: The prognostic role of high blood pressure and the aggressiveness of blood pressure lowering in dementia are not well characterized. OBJECTIVE: To assess whether office blood pressure, ambulatory blood pressure monitoring, or the use of antihypertensive drugs (AHDs) predict the progression of cognitive decline in patients with overt dementia and mild cognitive impairment (MCI). DESIGN, SETTING, AND PARTICIPANTS: Cohort study between June 1, 2009, and December 31, 2012, with a median 9-month follow-up of patients with dementia and MCI in 2 outpatient memory clinics. MAIN OUTCOMES AND MEASURES: Cognitive decline, defined as a Mini-Mental State Examination (MMSE) score change between baseline and follow-up. RESULTS: We analyzed 172 patients, with a mean (SD) age of 79 (5) years and a mean (SD) MMSE score of 22.1 (4.4). Among them, 68.0% had dementia, 32.0% had MCI, and 69.8% were being treated with AHDs. Patients in the lowest tertile of daytime systolic blood pressure (SBP) (≤128 mm Hg) showed a greater MMSE score change (mean [SD], -2.8 [3.8]) compared with patients in the intermediate tertile (129-144 mm Hg) (mean [SD], -0.7 [2.5]; P = .002) and patients in the highest tertile (≥145 mm Hg) (mean [SD], -0.7 [3.7]; P = .003). The association was significant in the dementia and MCI subgroups only among patients treated with AHDs. In a multivariable model that included age, baseline MMSE score, and vascular comorbidity score, the interaction term between low daytime SBP tertile and AHD treatment was independently associated with a greater cognitive decline in both subgroups. The association between office SBP and MMSE score change was weaker. Other ambulatory blood pressure monitoring variables were not associated with MMSE score change. CONCLUSIONS AND RELEVANCE: Low daytime SBP was independently associated with a greater progression of cognitive decline in older patients with dementia and MCI among those treated with AHDs. Excessive SBP loweringmay be harmful for older patients with cognitive impairment. Ambulatory blood pressure monitoring can be useful to help avoid high blood pressure overtreatment in this population. Copyright 2015 American Medical Association. All rights reserved.


Bartolotti M.,Azienda Unita Sanitaria Locale | Franceschi E.,Azienda Unita Sanitaria Locale | Brandes A.A.,Azienda Unita Sanitaria Locale
Expert Review of Anticancer Therapy | Year: 2012

The incidence of brain metastasis (BM) is high in patients with non-small-cell lung cancer. Available standard therapeutic options, such as whole-brain radiation therapy and systemic chemotherapy, provide a slight improvement in local control, overall survival and symptom relief. Novel agents, such as EGF receptor (EGFR) tyrosine kinase inhibitors (TKIs), have now been included in standard non-small-cell lung cancer treatments. In a small subset of patients harboring EGFR-activating mutations, erlotinib and gefitinib administration was followed by a response rate of 70-80%, and a longer progression-free and overall survival than those obtained with standard chemotherapeutic regimens. However, since most of the larger studies on these agents have excluded BM patients from their series, few prospective data are available on the efficacy of these agents in this setting. In recent years, however, several authors have reported a growing number of cases of partial and complete response in BM patients treated with EGFR TKIs. Data from retrospective series and Phase II studies also suggest that a response can be obtained using EGFR TKI treatment for patients with BM, especially those harboring EGFR mutations. © 2012 2012 Expert Reviews Ltd.


Bartolotti M.,Azienda Unita Sanitaria Locale | Franceschi E.,Azienda Unita Sanitaria Locale | Poggi R.,Azienda Unita Sanitaria Locale | Tosoni A.,Azienda Unita Sanitaria Locale | And 2 more authors.
Future Oncology | Year: 2014

Angiogenesis is a key process for tumoral growth, which has become a main target for anticancer treatments. A wide number of agents targeting both VEGF and its receptor have recently become standard treatments for different tumor types. Unfortunately, most of the tumors become resistant to these agents after few months of treatment. Different mechanisms of resistance to antiangiogenic drugs have been proposed and investigated; some agents demonstrated to be able to restore sensitivity to antiangiogenic drugs by blocking pathways or molecules involved in the resistance in preclinical models. Biomarkers for the prediction of response or resistance to antiangiogenic agents are under evaluation. © 2014 Future Medicine Ltd.


Situs viscerum inversus totalis is a rare defect with a genetic predisposition, which can present difficulties in the management of abdominal pathology, especially in laparoscopic surgery (mirror-image anatomy). We report the case of a 52-year-old female with situs viscerum inversus totalis, known from pediatric age, with a medical history of colic pain in the epigastrium radiating to the right abdominal quadrant. Laparoscopic cholecistectomy was safely performed with a three trocar technique. To the best of our knowledge this is the first time that laparoscopic cholecistectomy by three trocars was performed in a patient with situs viscerum inversus. We also review the relevant literature concerning this issue.


Manuguerra R.,University of Parma | Callegari S.,Azienda Unita Sanitaria Locale | Corradi D.,University of Parma
Journal of Cardiovascular Electrophysiology | Year: 2016

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.

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