ogadro University

Novara, Italy

ogadro University

Novara, Italy

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PubMed | ogadro University, Palermo Local Health Unit, Unit of Clinical Pharmacology, Local Health Authority ULSS and 6 more.
Type: Journal Article | Journal: BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy | Year: 2016

Granulocyte colony-stimulating factors (G-CSFs) are biological products for which the main indication of use is chemotherapy-induced neutropenia. Biosimilars of G-CSFs have been available in Europe since 2007.The objective of this study was to investigate the prescribing pattern of G-CSFs in five Italian centres using different healthcare policy interventions to promote the use of biosimilars in routine care.This retrospective, population-based drug utilization study was conducted during the years 2009-2014 using the administrative databases of the Caserta, Treviso and Palermo Local Health Units (LHUs) and the Tuscany and Umbria regions. G-CSF users were characterized and the prevalence of use, proportion of biosimilar users and switching pattern of different G-CSFs were evaluated over time and across centres.Overall, 30,247 patients were treated with G-CSFs in the years 2009-2014, of which 29,083 (96.2%) were nave users. The overall prevalence of G-CSF use increased from 0.8 per 1000 inhabitants in 2009 to 1.1 per 1000 in 2014. An increase in the proportion of the use of the biosimilar filgrastim by the total G-CSF users was observed in all centres: from 0.2% (2009) to 66.2% (2014). However, heterogeneity across different centres was reported, with the largest increase in Treviso LHU (from 0 to 89.1% from 2009 to 2014). During the first year of treatment, switching between different G-CSFs was frequent (20.3%).Heterogeneity in the use of G-CSF and, in particular, biosimilar filgrastim across different Italian centres was observed, probably due to different regional healthcare policy interventions. During the first year of treatment, switching between different G-CSFs was frequent. Considering the impact of biological drugs on pharmaceutical expenses, it is necessary to harmonize healthcare policies promoting the use of biological drugs with the lowest cost.


Viana M.,National Science Foundation | Genazzani A.A.,ogadro University | Terrazzino S.,ogadro University | Nappi G.,National Science Foundation | Goadsby P.J.,University of California at San Francisco
Cephalalgia | Year: 2013

Background: Triptans represent the best treatment option for most migraine attacks, although this is not as well studied as it might be in controlled trials. Their efficacy and tolerability vary, both between agents, and from patient to patient, with about 30%-40% of patients not responding adequately to therapy. As yet unexplained, the failure of one triptan does not predict failure with another, and therefore triptan nonresponders cannot be defined as individuals who have failed a single triptan. Five clinical studies provide evidence that switching from a triptan that is ineffective to a second one can result in effective treatment in a proportion of patients. Systematic studies investigating whether there are patients who do not respond to all triptans in all formulations are lacking. Methods: Here we discuss the importance of identifying triptan nonresponders, the literature supporting their existence, and the issues to be resolved to design trials to investigate this. Conclusion: So far, no scientific data about the presence of a triptan nonresponder population are available.We propose a pragmatic study design to assess the existence of this subpopulation, recognizing the complexity of the question and the likelihood that more than one issue is at play in nonresponders. © 2013 International Headache Society.


Corrado L.,The Interdisciplinary Center | Del Bo R.,University of Milan | Castellotti B.,Fondazione IRCCS Instituto Neurologico Carlo Besta | Ratti A.,University of Milan | And 18 more authors.
Journal of Medical Genetics | Year: 2010

Background Mutations in the FUS gene have recently been discovered to be a major cause of familial amyotrophic lateral sclerosis (FALS). Objective To determine the identity and frequency of FUS gene mutations in a large cohort of Italian patients enriched in sporadic cases (SALS). Methods Exons 5, 6, 14 and 15 of the FUS gene were screened for mutations in 1009 patients (45 FALS and 964 SALS). The genetic analysis was extended to the entire coding sequence of FUS in all the FALS and 293 of the SALS patients. Results Seven missense mutations (p.G191S, p.R216C, p.G225V, p.G230C, p.R234C, p.G507D and p.R521C) were identified in nine patients (seven SALS and two FALS), and none in 500 healthy Italian controls. All mutations are novel except for the p.R521C mutation identified in one SALS and one FALS case. Both patients showed a similar unusual presentation, with proximal, mostly symmetrical, upper limb weakness, with neck and axial involvement. With the exception of p.G507D and p.R521C, the mutations identified in SALS patients are all localised in the glycine-rich region encoded by exon 6. In addition, eight different in-frame deletions in two polyglycine motifs were detected, the frequency of which was not significantly different in patients and controls. Conclusions The results show that FUS missense mutations are present in 0.7% of Italian SALS cases, and confirm the previous mutational frequency reported in FALS (4.4%). An unusual proximal and axial clinical presentation seems to be associated with the presence of the p.R521C mutation.


PubMed | Science Farmaceutica Territoriale, University of Pavia, National Institute of Health, ogadro University and Headache Science Center ndino National Neurological Institute
Type: Journal Article | Journal: Cephalalgia : an international journal of headache | Year: 2015

In this drug utilization study, we aimed at assessing the pattern of triptan use in Italy by means of the drug prescription databases of two local health authorities, accounting for approximately 1 million citizens.The study population included all residents aged 18 to 84 years in the Vercelli province (about 175,000 inhabitants) and in the Umbria region (about 885,000 inhabitants), who had at least one dispensation for triptans in 2012. A frequent user, who might be at risk of medication-overuse headache (MOH), was defined as a patient being dispensed at least 10 defined daily doses (DDD) of triptans every month for at least three consecutive months.Triptans were used by 0.7%-1% of the population. While most patients were dispensed fewer than 60 DDDs per year, about 10% of all triptan users were classified as frequent users. In both areas, patients below the age of 29 were less likely to be frequent users while the 40- to 49-year-old population was the most affected, with no sex difference. About two-thirds of frequent users persisted in this behavior for an additional three-month period in the following six months.Our data indicate that approximately 10% of all triptan users in the Italian population are potentially at risk for MOH. An approach based on drug prescription databases could be useful to identify patients at risk for MOH.


Morani F.,ogadro University | Pagano L.,ogadro University | Prodam F.,ogadro University | Aimaretti G.,ogadro University | Isidoro C.,ogadro University
Panminerva Medica | Year: 2012

Aim. Molecular imaging diagnosis with FDG-PET ( 18F- fluorodeoxyglucose positron emission tomography with computed tomography) can reveal the presence of un-suspected thyroid cancer that are referred to as "incidentaloma" because of the incidental finding. The glucose analogue 18FDG is internalized in the cells by glucose transporters belonging to the GLUTs family. The surface expression of GLUT is under the control of the PI3k/Akt pathway. PTEN is an oncosuppressor frequently mutated or deleted in thyroid cancers. The lipid phosphatase activity of wild type PTEN switches off the Akt pathway. Here we tested the hypothesis that PTEN expression might affect the surface expression of GLUTI and therefore influence the possibility of "incidental" detection of thyroid cancer based on FDG-PET. Methods. The biopsy of 8 patients, who were incidentally diagnosed with PTC by 18F-fluorodeoxyglucose positron emission tomography with computed tomography, was assayed by immunofluorescence for the co-expression of the PTEN oncosuppressor and of GLUTI. Results. Loss of PTEN expression was detected in the majority of investigated cases (N.=6/8). Strikingly, while the two PTEN positive cases were negative for GLUTI expression, the PTEN negative cases showed intense expression of GLUTI at the cell surface. Conclusion. The present observations, though made in a limited number of cases, suggest that PTEN negative thyroid cancers have high chances to be revealed as incidentalomas at FDG-PET.


Del Bo R.,University of Milan | Del Bo R.,IRCCS Foundation CaGranda Ospedale Maggiore Policlinico | Tiloca C.,IRCCS Instituto Auxologico Italiano | Pensato V.,Fondazione IRCCS Instituto Neurologico Carlo Besta | And 16 more authors.
Journal of Neurology, Neurosurgery and Psychiatry | Year: 2011

Background: Optineurin (OPTN), a causative gene of hereditary primary open-angle glaucoma, has been recently associated with amyotrophic lateral sclerosis (ALS) with mainly autosomal recessive, but also dominant, traits. To further define the contribution of OPTN gene in ALS, we performed a mutational screening in a large cohort of Italian patients. Methods: A group of 274 ALS patients, including 161 familial (FALS) and 113 sporadic (SALS) cases, were screened for OPTN mutations by direct sequencing of its coding sequence. All patients fulfilled the El Escorial criteria for probable or definite ALS and were negative for mutations in SOD1, ANG, TARDBP and FUS/TLS genes. Results: The genetic analysis revealed six novel variants in both FALS and SALS patients, all occurring in an heterozygous state. We identified three missense (c.844A→C p.T282P, c.941A→T p.Q314L, c.1670A→C p.K557T), one nonsense (c.67G→T p. G23X) and two intronic mutations (c.552+1delG, c.1401 +4A→G). The intronic c.552+1delG variant determined a splicing defect as demonstrated by mRNA analysis. All mutations were absent in 280 Italian controls and over 6800 worldwide glaucoma patients and controls screened so far. The clinical phenotype of OPTN-mutated patients was heterogeneous for both age of onset and disease duration but characterised by lower-limb onset and prevalence of upper motor neuron signs. Conclusion: In this cohort, OPTN mutations were present both in FALS (2/161), accounting for 1.2% cases, and in SALS patients (4/113), thereby extending the spectrum of OPTN mutations associated with ALS. The study further supports the possible pathological role of optineurin protein in motor neuron disease.


Chio A.,University of Turin | Calvo A.,University of Turin | Mazzini L.,University of Piemonte Orientale | Cantello R.,University of Piemonte Orientale | And 14 more authors.
Neurology | Year: 2012

Objective: To assess the frequency and clinical characteristics of patients with mutations of major amyotrophic lateral sclerosis (ALS) genes in a prospectively ascertained, population-based epidemiologic series of cases. Methods: Thestudy population includes allALScases diagnosed in Piemonte, Italy, from January2007to June 2011. Mutations of SOD1, TARDBP, ANG, FUS, OPTN, andC9ORF72have been assessed. Results: Out of the 475 patients included in the study, 51 (10.7%) carried a mutation of an ALS-related gene (C9ORF72, 32; SOD1, 10; TARDBP, 7; FUS, 1; OPTN, 1; ANG, none). A positive family history for ALS or frontotemporal dementia (FTD) was found in 46 (9.7%) patients. Thirty-one (67.4%) of the 46 familial cases and 20 (4.7%) of the 429 sporadic cases had a genetic mutation. According to logistic regression modeling, besides a positive family history for ALS or FTD, the chance to carry a genetic mutation was related to the presence of comorbid FTD (odds ratio 3.5; p = 0.001), and age at onset ≤54 years (odds ratio 1.79; p = 0.012). Conclusions: We have found that ̃11% of patients with ALS carry a genetic mutation, with C9ORF72 being the commonest genetic alteration. Comorbid FTD or a young age at onset are strong indicators of a possible genetic origin of the disease. © 2012 American Academy of Neurology.


Navalesi P.,ogadro University | Colombo D.,ogadro University | Dellacorte F.,ogadro University
Minerva Anestesiologica | Year: 2010

Neurally adjusted ventilatory assist (NAVA) is a form of partial ventilatory support wherein the machine applies positive pressure to the airway opening throughout each inspiration. In contrast to all other modes of ventilation, which adopt conventional pneumatic signals (flow, volume, and airway pressure) to drive and control the ventilator operation, NAVA utilizes the electrical activity of the diaphragm, which is the best available signal to estimate the respiratory drive and to trigger on and cycle off the delivery of the mechanical assistance and regulate its amount and intrabreath profile. With NAVA, therefore, the patient retains full control of the breathing pattern. Following the first description of NAVA ten years ago, various studies have been performed on this mode of ventilation, either in animal models, healthy subjects, or in adult and pediatric critically ill patients. These investigations indicate that this novel mode is efficient in unloading the respiratory muscles and maintaining adequate gas exchange while improving the patientventilator interaction. This review article aims to summarize the results of the studies published to date on this topic.


Corrado L.,The Interdisciplinary Center | Mazzini L.,ogadro University | Oggioni G.D.,ogadro University | Luciano B.,The Interdisciplinary Center | And 4 more authors.
Human Genetics | Year: 2011

It has recently been suggested that short expansions of CAG repeat in the gene ATXN-2 causing SCA2 (spinocerebellar ataxia type 2) are associated with an increased risk of amyotrophic lateral sclerosis (ALS) in the populations of the USA and northern Europe. In this study, we investigated the role of ATXN-2 in Italian patients clinically diagnosed with ALS and characterized the molecular structure of ATXN-2 expansions. We assessed the size of the CAG repeat in ATXN-2 exon 1 in 232 Italian ALS patients and 395 matched controls. ATXN-2 expanded alleles containing[30 repeats have been observed in seven sporadic ALS patients (3.0%), while being absent in the controls (p = 0.00089). Four out of the seven patients had an ATXN-2 allele in the intermediate-fully pathological range: one with 32 repeats, 2 with 33 repeats and 1 with 37 repeats, accounting for 1.7% of the ALS cohort. Sequencing of expanded ([32) alleles showed that they were all interrupted with at least one CAA triplet. ATXN-2 alleles with the same length and structure have been reported in SCA2 patients with parkinsonism or in familial and sporadic Parkinson. Conversely, the phenotype of the present patients was typically ALS with no signs or symptoms of ataxia or parkinsonism. In conclusion, the findings of ATXN-2 expansions in pure ALS cases suggest that ALS may be a third phenotype (alongside ataxia/parkinsonism and pure Parkinson) associated with ATXN-2 interrupted alleles. © Springer-Verlag 2011.


PubMed | Unit of Biostatistics, Treviso Local Health Unit, Unit of Clinical Pharmacology, Messina University and ogadro University
Type: Journal Article | Journal: PloS one | Year: 2016

Since 2007 biosimilars of erythropoiesis-stimulating agents (ESAs) are available on the Italian market. Very limited post-marketing data exist on the comparative effectiveness of biosimilar and originator ESAs.This population-based study was aimed to compare the effects of biosimilars, reference product and other ESAs still covered by patent on hemoglobinemia in chronic kidney disease (CKD) and cancer patients in a Local Health Unit (LHU) from Northern Italy.A retrospective cohort study was conducted during the years 2009-2014 using data from Treviso LHU administrative database. Incident ESA users (no ESA dispensing within 6 months prior to treatment start, i.e. index date (ID)) with at least one hemoglobin measurement within one month prior to ID (baseline Hb value) and another measurement between 2nd and 3rd month after ID (follow-up Hb value) were identified. The strength of the consumption (as total number of defined daily dose (DDD) dispensed during the follow-up divided by days of follow-up) and the difference between follow-up and baseline Hb values [delta Hb (Hb)] were evaluated. Based on Hb changes, ESA users were classified as non-responders (Hb0 g/dl), responders (02 g/dl). A multivariate ordinal logistic regression model to identify predictors for responsiveness to treatment was performed. All analyses were stratified by indication for use and type of dispensed ESA at ID.Overall, 1,003 incident ESA users (reference product: 252, 25.1%; other ESAs covered by patent: 303, 30.2%; biosimilars: 448, 44.7%) with CKD or cancer were eligible for the study. No statistically significant difference in the amount of dose dispensed during the follow-up among biosimilars, reference product and other ESAs covered by patent was found in both CKD and cancer. After three months from treatment start, all ESAs increased Hb values on average by 2g/dl. No differences in Hb as well as in frequency of non-responders, responders and highly responders among different types of ESAs were observed in both indications of use. Overall, around 15-20% of ESA users were non-responders. Strength of treatment, but no type of dispensed ESAs was found to be predictor of responsiveness to treatment.No difference on the effects on hemoglobinemia among users of either biosimilars or reference product or ESAs covered by patent was observed in a general population from Northern Italy, despite a comparable dispensed dose of the different ESAs during the first three months of treatment.

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