Valutazione del management del paziente affetto da leucemia mieloide cronica nella pratica clinica dell'Azienda ULSS 2 marca trevigiana, distretto di Treviso Evaluation of the management of patients affected by chronic myeloid leukemia in the clinical practice of the Health Authority n.2 Marca Trevigiana, Distric of Treviso

Introduction Chronic myeloid leukemia (CML) is a myelodysplastic neoplasia accounting for around 15% of all cases of leukemia in adults. CML treatment is mainly based on tyrosine kinase inhibitors (TKIs). Current TKIs approved as first line treatments are imatinib or second-generation TKIs such as dasatinib and nilotinib. Overall, TKIs have modified the natural progression of CML, prolonging survival. As CML has progressively switched from a fatal to a âchronicâ pathology, time-limited clinical trials may not evaluate such long-term outcomes adequately. On the brink of the commercialization of generic imatinib, this thesis examines a decade of CML management in the real clinical practice, focusing on treatment effectiveness, therapeutic switches, and adverse effects (AEs). Methods A retrospective cohort study was performed on all CML patients followed up in the Local Health Authority of Treviso (Region of Veneto, Italy) between 2005 and 2015. Data were captured integrating both administrative databases and physicians' patient record. The therapeutic pattern was evaluated separately according to CML phase at diagnosis, considering frontline treatments, occurrence of treatment switches and their causes. For patients diagnosed in chronic phase (CP), the effectiveness of different frontline TKIs was assessed using an intention-to-treat approach, considering the achievement of complete hematologic, cytogenetic and molecular response. Occurrence of AEs among different frontline TKIs treatments was compared. All data and statistical analysis were performed using the software STATA version 14. Results A total cohort of 119 CML patients was examined; the majority of them were diagnosed in CP (n=97). 60% of subjects were asymptomatic at diagnosis; even when present, symptoms were mainly unspecific. Imatinib was the most common first line treatment for CP subjects (n=73); among second generation TKIs, only nilotinib was used as first line. Nilotinib proved more effective than imatinib, both considering achievement of responses and treatment switches; 28 CP-CML patients with frontline imatinib needed to switch, mainly due to intolerance but there were no therapeutic switches in patients with frontline nilotinib. AEs were common; in particular, osteoarticular pain was significantly more frequent for imatinib compared to nilotinib (50 out of 73 vs 2 out of 8, respectively; p=0.02). Conclusion Although based on a small population, this study shows the importance of choosing the most appropriate frontline treatment, in order to allow rapid disease control. Results indicate a superiority of nilotinib as first line therapy for CP-CML, both in terms of effectiveness and of treatment switches and AEs occurrence. While this might be seen as an argument to use nilotinib first line, it might also argue strongly for the continued use of imatinib first line, reserving nilotinib for imatinib intolerant or resistant patients. AEs remain a major concern, highlighting the importance of close monitoring of patients. A full health economic evaluation is required to determine the most cost effective care pathways using these expensive drugs

Behçet's Syndrome as a Model of Thrombo-Inflammation: The Role of Neutrophils

Behçet's syndrome (BS) is a systemic vasculitis, clinically characterized by different organ involvement and often complicated by thrombosis which occurs in vessels of all sizes. Thrombosis is more frequent in male patients with active disease and represents an important cause of morbidity and mortality. Neutrophil involvement in BS has been repeatedly suggested in the last few years. Indeed, neutrophils have been shown to be hyperactivated in BS patients, probably with a HLAB51 related contribution, and represent the main cells infiltrating not only oral and genital ulcers or erythema nodosum, but also other sites. Besides being deputed to host defense against micro-organisms, neutrophils display fundamental roles both in inflammation and tissue damage becoming inappropriately activated by cytokines, chemokines and autoantibodies and subsequently producing large amounts of superoxide anion (O2.) via NADPH oxidase (NOX2). The strict relationship between inflammation and hemostasis has been already demonstrated. Indeed, inflammation and immune-mediated disorders increase the risk of thrombosis, but the pathways that link these processes have not been completely elucidated. In this regard, we recently demonstrated, in a large population of BS patients, a new neutrophil-dependent pathogenetic mechanism of thrombosis. In particular, it was shown that neutrophils, mainly through NADPH oxidase, produce excessive amounts of reactive oxygen species (ROS), which are able to markedly modify the secondary structure of fibrinogen and hence the overall architecture of the fibrin clot that becomes less susceptible to plasmin-induced lysis. These data point out that BS represents “per se” a model of inflammation-induced thrombosis and suggest that neutrophils specifically contribute to thrombo-inflammation in this rare disease. In particular, it is suggested that an alteration in fibrinogen structure and function are associated with enhanced ROS production via neutrophil NADPH oxidase. Altogether, these findings improve our understanding of the intricate pathogenetic mechanisms of thrombo-inflammation and may indicate potential new therapeutic targets

Risk of bone fractures among users of oral anticoagulants: An administrative database cohort study

Occurrence of osteoporotic fracture in patients treated with oral anticoagulants was investigated. •Risk of fractures was comparable for warfarin and non vitamin K oral anticoagulants. •Independently from which OAC is used, female and elderly subjects were at higher risk of fractures

Real-practice thromboprophylaxis in atrial fibrillation

This retrospective observational study was based on databases of the Local Health Authority of Treviso, Italy. It evaluated the prevalence and the effectiveness of oral anticoagulation treatment (OAT) for the management of nonvalvular atrial fibrillation (NVAF) in everyday clinical practice. Out of 6,138 NVAF patients, only 3,024 received Vitamin K antagonist (VKA). Potential barriers decreasing the probability of being treated with VKA were female sex, older age, antiplatelet treatment and history of bleeding. In addition, VKA-treatment was not in line with current ESC and AIAC guidelines, since the patients at high or low risk of stroke were under-or over-treated, resp. Among VKAtreated patients, 73 % of subjects were not at target with anticoagulation. OAT resulted to be effective in reducing stroke risk. However, stroke events were significantly influenced also by previous stroke or transient ischemic attack (hazard ratio, HR = 2.99, p < 0.001) and by previous bleeding events (HR = 1.60, p < 0.001)

cost of illness study of diabetes mellitus focus on patients with type 2 diabetes

ObjectiveThe aim of the study was to assess the cost of management of diabetic patients; moreover, for type 2 not insulin-dependent patients, also the durability of treatments was evaluated, in ord..

dapagliflozin as add on to metformin network meta analysis and budget impact analysis

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The new era of anticoagulation: factor XI and XII inhibitors

The two last decades have witnessed a revolution in the field of anticoagulation, mainly due to the advent of direct anticoagulant with targeted action against single coagulation proteins. However, the residual risk of cardio- and cerebrovascular events, particularly in some critical settings, and the risk of major bleeding still represent unmet medical needs. Preclinical studies and experience from families with genetic deficiencies of factor XI or XII (FXI and FXII) allowed to identify these factors involved in the contact pathway of coagulation as potential targets for new anticoagulant approaches. To date, several pharmacological classes of FXI and FXII inhibitors have been developed, including antisense oligonucleotides, monoclonal antibodies, small molecules, natural inhibitors, and aptamers, and various molecules are currently under phase 2 or 3 clinical investigation. Particularly, promising results have been obtained in patients undergoing major orthopedic surgery, in those with end-stage kidney disease, atrial fibrillation and acute coronary syndrome. This review summarizes current knowledge on FXI and FXII inhibitors, with a particular focus on their pharmacological properties and potential clinical indications

Galenic Preparations of Therapeutic Cannabis sativa Differ in Cannabinoids Concentration: A Quantitative Analysis of Variability and Possible Clinical Implications

Introduction: Magistral preparations of therapeutic cannabis are extracted from standardized products imported from Holland or from the Florence Military Pharmaceutical Chemical Works, but extraction protocols differ among galenic laboratories. This study assessed the inter-laboratory variability in concentrations of cannabidiol (CBD), cannabinol (CBN), tetrahydrocannabinol (THC), and tetrahydrocannabinolic acid (THCA) among different magistral oil preparations.Methods: 219 samples of Bediol, Bedrobinol, Bedrolite or FM-2 70 or 100 mg/ml in oil were collected from 3 laboratories. Concentrations of CBD, CBN, THC, and THCA were quantified by high-pressure liquid chromatography; inter-laboratories variability was assessed using the Kruskal–Wallis test.Results: A significant variability in CBD and THC concentrations was found for Bediol 70 mg/ml samples from 2 laboratories [for CBD: median 5.4 (range 4.8–6.6) vs. 6.1 (4.9–7.2) mg/ml, p = 0.033; for THC: 3.6 (3.1–3.9) vs. 4.0 (2.6–5.1) mg/ml, p = 0.020]. As for Bediol 100 mg/ml, a significant variability emerged in THC concentrations among the three considered laboratories [5.7 (-) vs. 4.2 (1.5–4.8) vs. 5.2 (4.2–6.9), p = 0.030]. No significant inter-laboratory variability emerged for Bedrocan and Bedrolite. Concentrations of CBD, CBN, and THC were &lt;LOQ in all Bedrocan samples, and CBN and THCA were &lt;LOQ in all Bedrolite samples. As for FM-2, a significant inter-laboratories variability was found for CBD concentrations.Conclusion: Quantitative variability of cannabinoids in magistral preparations might impact on the efficacy and safety of therapeutic cannabis. A standardized protocol is needed to guarantee a homogeneous product and patients’ therapeutic continuity