Pharmacoutilization of epoetins in na\uc3\uafve patients with hematological malignancies in an unselected italian population under clinical practice setting: A comparative analysis between originator and biosimilars

Aim: The purpose of this study was to assess the prescription of epoetins and consumption of health care resources (in terms of drug treatments) in na\uc3\uafve patients with hematological malignancies in a real-world setting; in particular, we compared the results between reference product and biosimilar products. Methods: An observational retrospective study based on administrative and laboratory databases of three local health units was conducted. All adults diagnosed with hematological malignancies and who had received at least one epoetin (either reference product or biosimilars) prescription for the first time between 1 January 2010 and 30 April 2012 (enrollment period) were included. The date of the first prescription of epoetin within the enrollment period was defined as index date (ID). Patients were followed up for 4 weeks after ID (follow-up period) and were investigated for the 1-year period before the ID. The difference between the last hemoglobin (Hb) measurement after ID and the one prior to ID (\uce\u94Hb) was evaluated. The drug cost analysis was conducted from the perspective of the Italian National Health System. Results: Overall, 69 patients were included in the study; 48 of them received reference epoetin product and 21 received biosimilars as first prescription. Among reference product users, the mean \uc2\ub1 standard deviation (SD) age was 62.5\uc2\ub114.7 years; this cohort of patients was slightly significantly younger than the biosimilar users (71.8\uc2\ub111.8 years). The mean \uc2\ub1SD overall Hb level prior to treatment was lower among patients who started with biosimilar products (9.6\uc2\ub11.1 g/dL) compared to those who started with a reference product (10.1\uc2\ub12.1 g/dL). No significant differences in \uce\u94Hb were observed between biosimilar and originator groups during the followup period. The mean \uef\u82\u81\uef\u81\ubd\uef\u80 SD cost per patient was \ue2\u82\uac667.98\uc2\ub1573.93 and \ue2\u82\uac340.85\uc2\ub1235.73 for the reference product and biosimilar users, respectively (p=0.065). Conclusion: Our study showed that the use of biosimilar products might contribute to controlling health care costs (in terms of drug treatments) for patients with hematological malignancies being maintained by high-quality anemia therapy. Our findings also showed some discordances regarding the most appropriate therapeutic approach in daily clinical practice

The impact of different doses of indocyanine green on the sentinel lymph-node mapping in early stage endometrial cancer.

INTRODUCTION Aim of the study is to evaluate the impact of different doses of indocyanine green (ICG) on the sentinel lymph-node (SLN) mapping in endometrial cancer (EC). MATERIALS AND METHODS A retrospective analysis of EC patients undergoing a laparoscopic SLN mapping at two institutions was performed. Two different injection protocols were used (protocol # 1: 5 mg/ml and a volume of 8 ml; protocol # 2: 1.25 mg/ml and a volume of 4 ml). In every case, the injection was intracervical. The laparoscopic equipment adopted was the same among both institutions. Overall and bilateral detection rates (DR) and median number of retrieved SLNs were calculated. At uni- and multivariate analysis factors (including ICG dose) associated with DR and number of detected SLNs were investigated. RESULTS Overall, 168 patients were included. The overall and bilateral DR were 96.3 and 84.5%. Median number of removed SLNs was 3 (0-18). In 56% of the patients, a median number of 6 (1-93) non-SLNs (NSLNs) were removed. Seventeen (10.1%) patients had metastatic SLNs. At multivariate analysis, no factors were associated with bilateral DR. ICG dose was the only factor associated with number of removed SLNs at multivariate analysis. CONCLUSION A larger dose of ICG is associated with a higher number of retrieved SLNs but not with an increased bilateral DR

ajcr0000112d

Abstract: Epithelial ovarian cancer is a malignancy with high rate of death due to an advanced disease at diagnosis and frequent relapse after chemotherapy. Nowadays, there is a lack of knowledge for clear risk factors and predictive and/or prognostic genetic markers although genomic alterations such as mutations in p53, PTEN, BRCA1/BRCA2, HER2, KRAS and PI3K genes have been associated to this pathology. A genomic variant in the 3' untraslated region of cancer related gene KRAS, is able to disrupt the let-7 miRNA binding site. The SNP, commonly named KRAS-LCS6, determines the substitution of the more abundant T-allele to a G-allele which was observed to increase the KRAS expression and in turn to activate the downstream pathway at higher levels if compared to the T-allele. In this study we assessed the role of the KRAS-LCS6 polymorphism (rs61764370) in 97 early (stages I and II) and 232 advanced (stages III and IV) ovarian cancer patients in order to associate this SNP to any physiopathological characteristic of the patients cohort, including progression free survival and overall survival, with a follow up data longer than ten years. Our data indicate that KRAS-LCS6 polymorphism is not relevant in ovarian cancer, in fact, in our cohort of patients, is not associated to any outcome or physiopathological characteristic

La farmacoutilizzazione delle statine nella pratica clinica: risultati di uno studio di popolazione condotto su database amministrativi e di medici di medicina generale

In spite of findings of large-scale clinical trials which showed an overall reduction of morbidity and mortality from coronary heart disease in patients treated with 3-hydroxy-3-metylglutaryl coenzyme-A reductase inhibitors (statins), relatively little is still known about the real prevalence of treatment in general practice setting, particularly in patients with a high cardiovascular risk. The objective of this study was to investigate among patients with cardiovascular risk profile estimated according to the Framingham Heart Prediction Risk Study, the percentage of those exposed to statins, and the proportion of patients reaching total cholesterol (TC) target levels. A cross-sectional analysis was conducted on a large cohort of patients listed in the administrative databases of the Local Health Unit of Ravenna (total resident population of 356,000). In 2001, every single patient who received a prescription for a statin, and/or with a recorded plasma TC level, and/or with a hospital admission for cardiovascular reasons (identified by ICD-9 code), and/or with a clinical appraisal based on the presence of cardiovascular risk factors, was defined eligible. Sebsequently, pharmaceutical, and nosocomial databases, were cross-linked with that of 50 general practitioners in order to assess the pharmacoutilization of statins on a patient-by-patient basis. A cohort of 9,208 patients with a well documented cardiovascular risk profile were analyzed. The mean age of those patients was 57 (SD=17) years and 42% of them was male. On the basis of raised TC levels and cardiovascular risk profiles, patients for whom a statin treatment was suggested amounted to 7,233. However, the number of those who received statins was significantly lower (n = 1,343), corresponding to 18.6%. In those exposed to statins, just a small group of patients reached a level of TC below 190 mg/dl (n = 271), equivalent to 20.2%. In the group of treated who did not achieve recommended TC target levels, 31.7% (n = 340) of patients was at very high cardiovascular risk. Moreover, among all patients with high plasma TC levels (n=5,890), there was a 45.7% (n = 2,690) who did not received any lipid lowering drug even though they had a high cardiovascular risk profile. Results from large population-based administrative databases suggest a remarkable level of undertreatment among patients with cardiovascular risk factors. Furthermore, many patients did not achieve recommended TC target levels with their statin treatment. Pharmacoutilization of statins in general practice reveals the need of a more careful pursuing of therapeutic goals

Room temperature chiral magnetic skyrmion in ultrathin magnetic nanostructures

Magnetic skyrmions are chiral spin structures with a whirling configuration. Their topological properties, nanometer size and the fact that they can be moved by small current densities have opened a new paradigm for the manipulation of magnetisation at the nanoscale. To date, chiral skyrmion structures have been experimentally demonstrated only in bulk materials and in epitaxial ultrathin films and under external magnetic field or at low temperature. Here, we report on the observation of stable skyrmions in sputtered ultrathin Pt/Co/MgO nanostructures, at room temperature and zero applied magnetic field. We use high lateral resolution X-ray magnetic circular dichroism microscopy to image their chiral N\'eel internal structure which we explain as due to the large strength of the Dzyaloshinskii-Moriya interaction as revealed by spin wave spectroscopy measurements. Our results are substantiated by micromagnetic simulations and numerical models, which allow the identification of the physical mechanisms governing the size and stability of the skyrmions.Comment: Submitted version. Extended version to appear in Nature Nanotechnolog

Genetics and molecular epidemiology of multiple myeloma : the rationale for the IMMEnSE consortium (review)

There is strong evidence suggesting the presence of a genetic component in the aetiology of multiple myeloma (MM). However no genetic risk factors have been unequivocally established so far. To further our understanding of the genetic determinants of MM risk, a promising strategy is to collect a large set of patients in a consortium, as successfully done for other cancers. In this article, we review the main findings in the genetic susceptibility and pharmacogenetics of MM and present the strategy of the IMMEnSE (International Multiple Myeloma rESEarch) consortium in contributing to determine the role of genetic variation in pharmacogenetics and in MM risk.We acknowledge support by the recruiting hospitals and physicians of the study regions as well as their collaborating nurses and technicians. Collection of blood samples from Spain, patients from Granada area and DNA extraction was partially supported by grants P08-CVI-4116 from Consejeria de Salud de la Junta de Andalucia (Sevilla, Spain) and PI081051 from Fondo de Investigaciones Sanitarias (Madrid, Spain). Collection of blood samples from Polish patients and controls from Lodz area and DNA extraction was supported by a grant from Polish Ministry of Science and Higher Education (No. N N402178334)

Analisi della persistenza e delle risorse allocate nel trattamento farmacologico dell’ipertensione arteriosa

In this study, the persistence with treatment and resources allocated in antihypertensive pharmacotherapy has been evaluated. Administrative databases of the Local Health Unit of Ravenna listing patients baseline characteristics, drug prescriptions and hospital admissions were used to perform a population-based retrospective study. All new users 20 years old or over receiving a first prescription for diuretics, beta-blockers, calcium channel-blockers, ACE inhibitors or AII-Antagonists between January 1st, 1997 and December 31st, 1997 were included. A one-year follow-up for prescriptions of anti-hypertensive drugs were considered. According to duration of therapy, treated population was divided in persistent patients (continuers and switchers) and non-persistent patients. A total of 16,783 patients was included in the study of whom 64.9% were non-persistents. Persistence with treatment seems to be associated with the class of anti-hypertensive drug initially prescribed, and with patient-related factors. Patients initially prescribed for AII-Antagonists were more likely to persist than those starting on the other antihypertensive classes. Annual antihypertensive treatment cost accounted for • 1,076,053.55 of which 25.4% for non-persistent patients. An appropriate use of claims data may be considered as a powerful tool, providing detailed epidemiological and economic information concerning the antihypertensive treatment

Management of Patients Diagnosed with Endometrial Cancer: Comparison of Guidelines

: Endometrial cancer is the most common gynecological malignancy in Europe and its management involves a variety of health professionals. In recent years, big discoveries were made concerning the management of patients diagnosed with endometrial cancer, particularly in the field of molecular biology and minimally invasive surgery. This requires the continuous updating of guidelines and protocols over the years. In this paper, we aim to summarize and compare common points and disparities among protocols for management of patients diagnosed with endometrial cancer by leading international gynecological oncological societies. We therefore systematically report the parallel among the guidelines based on the various steps patients with endometrial cancer usually undergo. The comparison between American and European protocols revealed some relevant disparities, in particular regarding surgical staging, molecular biology application as a prognostic tool and follow up regimens. This could possibly cause differences in interpreting and applying protocols in clinical practice in small centers, leading to a lack of adherence to guidelines or even prompting a confusing mix of them

Carfilzomib, lenalidomide, and dexamethasone in relapsed refractory multiple myeloma: a prospective real-life experience of the Regional Tuscan Myeloma Network

IntroductionCarfilzomib, a potent, irreversible, selective proteasome inhibitor has demonstrated consistent results in relapsed/refractory multiple myeloma (RRMM) combined with lenalidomide and dexamethasone (KRd). No prospective studies are yet available that analyzed the efficacy of the KRd combination.MethodsHerein, we report a multicenter prospective observational study on 85 patients who were treated with KRd combination as the second or third line of treatment, according to standard practice.ResultsThe median age was 61 years; high-risk cytogenetic was found in 26% and renal impairment (estimated glomerular filtration rate (eGFR) <60 ml/min) in 17%. After a median follow-up of 40 months, patients received a median number of 16 cycles of KRd, with a median duration of treatment (DoT) of 18 months (range, 16.1–19.2 months). The overall response rate was 95%, with a high-quality response (≥very good partial remission [VGPR]) in 57% of the patients. The median progression-free survival (PFS) was 36 months (range, 29.1–43.2 months). Achievement of at least VGPR and a previous autologous stem cell transplantation (ASCT) were associated with longer PFS. The median overall survival (OS) was not reached (NR); the 5-year OS rate was 73%. Nineteen patients underwent KRd treatment as a bridge to autologous transplantation, obtaining a post-transplant minimal residual disease (MRD) negativity in 65% of cases. The most common adverse events were hematological, followed by infection and cardiovascular events, rarely G3 or higher, with a discontinuation rate for toxicities of 6%. Our data confirmed the feasibility and safety of the KRd regimen in real life