16 research outputs found
Comparative Effectiveness of Biosimilar, Reference Product and Other Erythropoiesis-Stimulating Agents (ESAs) Still Covered by Patent in Chronic Kidney Disease and Cancer Patients: An Italian Population-Based Study
Background 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. Aim 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. Methods 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 (ÎHb)] were evaluated. Based on Hb changes, ESA users were classified as non-responders (ÎHbâ¤0 g/dl), responders (0Delta;Hbâ¤2 g/dl), and highly responders (ÎHb>2 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. Results 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 ÎHb 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. Conclusions 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
Myeloperoxidase-dependent oxidation of etoposide in human myeloid progenitor CD34+ cells
ABSTRACT Etoposide is a widely used anticancer drug successfully utilized for treatment of many types of cancer in children and adults. Its use, however, is associated with an increased risk of development of secondary acute myelogenous leukemia (t-AML) involving MLL gene MOL #68718
Vaccination coverage in healthcare workers: a multicenter cross-sectional study in Italy
IntroductionIn recent years, a phenomenon known as "vaccine hesitancy" has spread throughout the world, even among health workers, determining a reduction in vaccination coverage (VC). A study aimed at evaluating VC among healthcare workers (HCWs) in 10 Italian cities (L'Aquila, Genoa, Milan, Palermo, Sassari, Catanzaro, Ferrara, Catania, Naples, Messina) was performed.Materials and methodsAnnex 3 of the Presidential Decree n. 445 of 28 December 2000 was used to collect information on the vaccination status of HCWs. The mean and standard deviation (SD) were calculated with regard to the quantitative variable (age), while absolute and relative frequencies were obtained for categorical data (sex, professional profile, working sector, vaccination status). The connection between VC and the categorical variables was evaluated by chi-square method (statistical significance at p<0.05). The statistical analyses were performed by SPSS and Stata software.ResultsA total of 3,454 HCWs participated in the project: 1,236 males and 2,218 females. The sample comprised: physicians (26.9%), trainee physicians (16.1%), nurses (17.2%) and other professional categories (9.8%). Low VC was generally recorded. Higher VC was found with regard to polio, hepatitis B, tetanus and diphtheria, while coverage was very low for measles, mumps, rubella, pertussis, chickenpox and influenza (20-30%). ConclusionsThis study revealed low VC rates among HCWs for all the vaccinations. Measures to increase VC are therefore necessary in order to prevent HCWs from becoming a source of transmission of infections with high morbidity and/or mortality both within hospitals and outside
Sintesi e reattivitĂ di complessi piridinimminici di platino (II) funzionalizzati
Nel presente lavoro di tesi, inquadrato in una linea di ricerca che da anni si occupa dello sviluppo di composti di platino con potenziale attivitĂ antiproliferativa nei confronti di cellule tumorali, sono stati sintetizzati nuovi complessi imminopiridinici di platino (II) di formula generale cis-[PtCl2 (NâNâ)]. Questi composti sono stati caratterizzati mediante spettroscopia 1H, 13C e 195Pt NMR, spettroscopia IR-ATR e ne è stato determinato il contenuto di C, H ed N.
Come precursori per la sintesi del legante sono state scelte delle diammine simmetriche con catene idrocarburiche a diversa lunghezza (C3, C6, C8): la presenza della funzionalitĂ amminica consente lâintroduzione di opportuni frammenti (ad esempio arilici) , nell'ottica di spostarci verso sistemi con effetti sinergici determinati dalla cooperazione del centro metallico e dei residui aggiunti. La presenza di una catena idrocarburica piuttosto lunga conferisce un'opportuna mobilitĂ conformazionale facilitando le interazioni non covalenti sul DNA da parte dei frammenti arilici.
La sintesi delle imminopiridine utilizzate come leganti chelanti del platino, ha richiesto lâiniziale mono protezione delle diammine utilizzate come precursore, seguita dalla condensazione con la piridin-2-carbaldeide. Lâagente protettore utilizzato è stato (BOC)2O (di-tert-butil dicarbonato) e tale procedura richiede diversi passaggi sintetici nonchĂŠ di purificazione. I nuovi sistemi di platino(II), ottenuti per reazione delle imminopiridine con cis-[PtCl2(DMSO)2] (DMSO= dimetilsolfossido), sono stati successivamente trattati con CF3COOH per rimuovere il gruppo protettivo dalla funzionalitĂ amminica; diversi sono stati i tentativi eseguiti al fine di liberare tale funzionalitĂ prima di ottenere lâesito desiderato.
La deprotezione porta ad avere un gruppo amminico nella forma salificata per cui sono state investigate diverse basi al fine di deprotonare lâazoto amminico; sono state testate basi come la piridina e NaHCO3. Questâultima ha dato risultati promettenti tanto da poter testare (mediante una prova preliminare) la reattivitĂ nei confronti dellâalchilazione; lâalchilante utilizzato è stato il bromuro di benzile. Lâidea di riuscire ad alchilare lâazoto amminico con residui aromatici di diversa dimensione offre (come giĂ detto in precedenza) lâopportunitĂ a questi nuovi sistemi di agire sul DNA mediante una doppia azione: platinazione e intercalazione.
Successivamente sono state condotte altre prove di reattivitĂ preliminari in cui è stato studiato il comportamento e la stabilitĂ in condizioni ossidanti di tali sistemi di Pt(II) contenenti leganti piridinimminici; lâossidante utilizzato è stato lo iodobenzene dicloruro. La reazione di ossidazione è stata seguita attraverso spettroscopia 195Pt- NMR e il sistema si è dimostrato stabile per cui la funzionalitĂ imminica coordinata al centro metallico viene mantenuta. Tale prova è fondamentale al fine di testare lâattivitĂ antiproliferativa e citotissica associabile a complessi di Pt(IV) i quali, essendo piĂš inerti, possono raggiungere lâambiente intracellulare senza subire prima trasformazioni chimiche e una volta nel citoplasma possono sfruttare lâambiente riducente e piĂš acido tipico delle cellule tumorali per ridursi a Pt(II) e attivarsi successivamente per idrolisi.
Un altro approccio sintetico è stato quello di preparare complessi dinucleari di Pt(II) ottenuti per reazione tra
cis-[PtCl2 (DMSO)2 ] e imminopiridine ottenute dalla stessa reazione di condensazione aldolica eseguita per la realizzazione dei complessi mononucleari di Pt(II), ma con un rapporto stechiomentrico differente, di 2:1 tra aldeide e complesso metallico. Anche in questo caso si può pensare ad una doppia strategia di attacco sul DNA in cui vi è una doppia platinazione
Analgesic hypnotic treatment in a post-stroke patient
: In recent years, hypnotic suggestions have been used in several clinical conditions. This treatment is often used for anxiety treatment, somatization, and post-traumatic stress disorder. Hypnotic analgesia is one of the most clinically useful phenomena of hypnosis. The article describes the case of a patient who underwent hypnotic treatments for hypersensitivity and chronic pain. Results showed an improvement of pain control and a decrease of pain hypersensibility. In addition, during rehabilitative treatments, the patient reported a high level of compliance with the multidisciplinary team. These findings suggest that hypnosis could be a useful treatment for post-stroke pain management
Myeloperoxidase-dependent oxidation of etoposide in human myeloid progenitor CD34+ cells
ABSTRACT Etoposide is a widely used anticancer drug successfully used for the treatment of many types of cancer in children and adults. Its use, however, is associated with an increased risk of development of secondary acute myelogenous leukemia involving the mixed-lineage leukemia (MLL) gene (11q23) translocations. Previous studies demonstrated that the phenoxyl radical of etoposide can be produced by action of myeloperoxidase (MPO), an enzyme found in developing myeloid progenitor cells, the likely origin for myeloid leukemias. We hypothesized, therefore, that one-electron oxidation of etoposide by MPO to its phenoxyl radical is important for converting this anticancer drug to genotoxic and carcinogenic species in human CD34 ĎŠ myeloid progenitor cells. In the present study, using electron paramagnetic resonance spectroscopy, we provide conclusive evidence for MPO-dependent formation of etoposide phenoxyl radicals in growth factor-mobilized CD34 ĎŠ cells isolated from human umbilical cord blood and demonstrate that MPO-induced oxidation of etoposide is amplified in the presence of phenol. Formation of etoposide radicals resulted in the oxidation of endogenous thiols, thus providing evidence for etoposide-mediated MPO-catalyzed redox cycling that may play a role in enhanced etoposide genotoxicity. In separate studies, etoposide-induced DNA damage and MLL gene rearrangements were demonstrated to be dependent in part on MPO activity in CD34 ĎŠ cells. Together, our results are consistent with the idea that MPO-dependent oxidation of etoposide in human hematopoietic CD34 ĎŠ cells makes these cells especially prone to the induction of etoposide-related acute myeloid leukemia
Myeloperoxidase-Dependent Oxidation of Etoposide in Human Myeloid Progenitor CD34+ Cells
Etoposide is a widely used anticancer drug successfully used for the treatment of many types of cancer in children and adults. Its use, however, is associated with an increased risk of development of secondary acute myelogenous leukemia involving the mixed-lineage leukemia (MLL) gene (11q23) translocations. Previous studies demonstrated that the phenoxyl radical of etoposide can be produced by action of myeloperoxidase (MPO), an enzyme found in developing myeloid progenitor cells, the likely origin for myeloid leukemias. We hypothesized, therefore, that one-electron oxidation of etoposide by MPO to its phenoxyl radical is important for converting this anticancer drug to genotoxic and carcinogenic species in human CD34+ myeloid progenitor cells. In the present study, using electron paramagnetic resonance spectroscopy, we provide conclusive evidence for MPO-dependent formation of etoposide phenoxyl radicals in growth factor-mobilized CD34+ cells isolated from human umbilical cord blood and demonstrate that MPO-induced oxidation of etoposide is amplified in the presence of phenol. Formation of etoposide radicals resulted in the oxidation of endogenous thiols, thus providing evidence for etoposide-mediated MPO-catalyzed redox cycling that may play a role in enhanced etoposide genotoxicity. In separate studies, etoposide-induced DNA damage and MLL gene rearrangements were demonstrated to be dependent in part on MPO activity in CD34+ cells. Together, our results are consistent with the idea that MPO-dependent oxidation of etoposide in human hematopoietic CD34+ cells makes these cells especially prone to the induction of etoposide-related acute myeloid leukemia
Mean strength of ESA treatment during the whole follow-up, stratified by indication for use and type of ESA.
<p>CKD = Chronic kidney disease; ESAs = Erythropoiesis-stimulating agents.</p
Responsiveness to ESA treatment, assessed as delta Hb (ÎHb) between follow-up and baseline Hb value, stratified by indication for use and type of ESA.
<p>Hb = hemoglobin; CKD = Chronic kidney disease; ESAs = Erythropoiesis-stimulating agents; Ref. Product = Reference Product.</p
Effect of ESAs on Hb measurements within the follow-up Hb value from the start of the treatment, stratified by indication for use.
<p>Hb = hemoglobin; CKD = Chronic kidney disease; ESAs = Erythropoiesis-stimulating agents.</p