Multicentric survey on dose reduction/interruption of cancer drug therapy in 12.472 patients: Indicators of suspected adverse reactions

Antiblastic drugs have a high number of potential side-effects. Paradoxically, according to the National Network of Pharmacovigilance, the number of reported adverse reactions to these agents is proportionally lower than that registered for non antiblastic drugs. Critical phenomena such as treatment interruptions and significant dose reductions within the first two months of use may be indicators of adverse drug reactions. The aim of the present study was to increase our knowledge of pharmacovigilance to facilitate the actions taken to improve the risk-benefit profile of cancer drugs and, consequently, their safety. This retrospective observational survey was carried out on prescriptions from 1st January 2012 to 31st December 2012.Dose reductions of more than 10% during the first 90 days of therapy were considered as a surrogate indicator of an adverse reaction. Dose interruptions during the first 60 days of therapy were taken into consideration. Of the12,472 patients 1,248 underwent a dose reduction. The drugs that most often required a dose reduction were paclitaxel and oxaliplatin (17.4% and 17.3%, respectively), docetaxel (14.8%), carboplatin (15%), fluorouracil (10.7%) and, among oral medications, capecitabine (6.9%). Of the 1896 patients treated with the same drugs, 9.7% interrupted treatment. Patients required a lower dose reduction than that reported by other authors. Around 15% of cases underwent a 30% dose reduction within three months of starting therapy, indicating a possible adverse reaction. Constant monitoring of dose prescription and continuous training of medical and nursing staff are clearly needed to increase awareness of the importance of reporting adverse events.Antiblastic drugs have a high number of potential side-effects. Paradoxically, according to the National Network of Pharmacovigilance, the number of reported adverse reactions to these agents is proportionally lower than that registered for non antiblastic drugs. Critical phenomena such as treatment interruptions and significant dose reductions within the first two months of use may be indicators of adverse drug reactions. The aim of the present study was to increase our knowledge of pharmacovigilance to facilitate the actions taken to improve the risk-benefit profile of cancer drugs and, consequently, their safety. This retrospective observational survey was carried out on prescriptions from 1st January 2012 to 31st December 2012. Dose reductions of more than 10% during the first 90 days of therapy were considered as a surrogate indicator of an adverse reaction. Dose interruptions during the first 60 days of therapy were taken into consideration. Of the12,472 patients 1,248 underwent a dose reduction. The drugs that most often required a dose reduction were paclitaxel and oxaliplatin (17.4% and 17.3%, respectively), docetaxel (14.8%), carboplatin (15%), fluorouracil (10.7%) and, among oral medications, capecitabine (6.9%). Of the 1896 patients treated with the same drugs, 9.7% interrupted treatment. Patients required a lower dose reduction than that reported by other authors. Around 15% of cases underwent a 30% dose reduction within three months of starting therapy, indicating a possible adverse reaction. Constant monitoring of dose prescription and continuous training of medical and nursing staff are clearly needed to increase awareness of the importance of reporting adverse events

Nosocomial acquisition of methicillin-resistant Staphyloccocus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL) Enterobacteriaceae in hospitalised patients: a prospective multicenter study

The risk of acquisition of antibiotic resistant-bacteria during or shortly after antibiotic therapy is still unclear and it is often confounded by scarce data on antibiotic usage.Primary objective of the study is to compare rates of acquisition of methicillin-resistant Staphylococcus aureus and extended spectrum beta-lactamase-producing Enterobacteriaceae in hospitalised patients, after starting antibiotic therapy

VIVO: a Secure, Privacy-Preserving, and Real-Time Crowd-Sensing Framework for the Internet of Things

Smartphones are a key enabling technology in the Internet of Things (IoT) for gathering crowd-sensed data. However, collecting crowd-sensed data for research is not simple. Issues related to device heterogeneity, security, and privacy have prevented the rise of crowd-sensing platforms for scientific data collection. For this reason, we implemented VIVO, an open framework for gathering crowd-sensed Big Data for IoT services, where security and privacy are managed within the framework. VIVO introduces the enrolled crowd-sensing model, which allows the deployment of multiple simultaneous experiments on the mobile phones of volunteers. The collected data can be accessed both at the end of the experiment, as in traditional testbeds, as well as in real-time, as required by many Big Data applications. We present here the VIVO architecture, highlighting its advantages over existing solutions, and four relevant real-world applications running on top of VIVO

Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P < 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P < 0.001), sNox2-dp (r(s), -0.57; P < 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P < 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation

Capecitabine in elderly patients with metastatic breast cancer

Aims and background Capecitabine is the reference treatment for anthracycline-and/or taxane-pretreated metastatic breast cancer (MBC). This study examined its efficacy, tolerability and impact on the quality of life of elderly patients with MBC. Materials and methods Between January 2002 and December 2009, 75 consecutive elderly patients with MBC received first-line chemotherapy with capecitabine 1000 mg/m2 twice daily for 14 days every 3 weeks. Endpoints were efficacy, tolerability and clinical-benefit response measured every 3 cycles. Results Median age was 76 years (range 65–88); median ECOG performance status was 1 (range 0–2); 51 patients (68%) had received adjuvant chemotherapy and all patients had received hormonal therapy. Median exposure was 6 cycles. After 3 cycles, 11 patients (14.7%) had a partial response, one patient experienced a complete response, and 49 patients (65.3%) had stable disease, amounting to a disease control rate of 81.3%. Stable disease was maintained in 45 patients (60%) after 6 cycles, in 21 patients (28%) after 9 cycles, and in 13 patients (17.3%) after 12 cycles. A clinical-benefit response was experienced by 42 patients (56%), indicating a positive impact on quality of life. Treatment was well tolerated, the most common grade 3 events being diarrhea (12%) hand-foot syndrome (8%), and mucositis (8%). Adverse events were managed with dose adjustments and supportive therapy when required. Conclusions Our results indicate that capecitabine is active and well tolerated in elderly patients with MBC. This dosing regimen warrants further study in the first-line setting for patients with less aggressive MBC who are not candidates for combination therapy. </jats:sec

Biostimulants for Sustainable Food Production: Effects of Wood Distillate to Fortify Chickpea Flour for Development of Functional Bakery Products

In recent years, chickpea flour has been incorporated into various food products for improving their protein content and nutritional values. Based on the ‘Farm to Fork’ strategy, the need for the reduction of chemical pesticides is pushing the use of biobased products for cultivation. Wood distillate (WD), a byproduct of woody biomass pyrolysis, has emerged as a biostimulant with positive effects on crop yield and quality. To achieve functional bakery products with improved antioxidant capacity enriched with proteins, we use flour from WD-treated chickpeas. WD treatment significantly increases the content of polyphenols and proteins, such as vicilin- and legumin-like proteins. After a simulated gastrointestinal digestion of the biscuits, the released peptides are analyzed. An improved number of peptides (460) released by WD-treated chickpea flour cookies has been detected compared with the control (286). Chickpea flour from a biostimulated plant offers a new perspective for the production of nutritionally enriched bakery products

Amyloid aggregates accumulate in melanoma metastasis modulating YAP

By exploring human biopsies from melanoma patients, we found the presence of protein aggregates specifically spread in metastasis compared to primitive lesions. Secretome analysis of metastatic melanoma cell lines revealed the release of amyloidogenic proteins as PMEL, APLP2, APLP1 and APP into the extracellular space. Proteins involved in amyloid maturation as APOE, QPCT, SORT1, VLDLR and DCT were also detected, attesting the presence of an active amyloidogenic machinery. Herein, we demonstrated that BACE activity regulates aggregates production, and its inhibition affects the shedding of the amyloid related proteins. We showed that BACE sheddome regulates extracellular matrix and activates mechanosignaling i.e. by impacting on YAP nuclear localization. Moreover, BACE inhibition impairs cells proliferation and enhances sensitivity to doxorubicin. These results suggest the importance of amyloids production for tumor survival, highlighting the potential of BACE inhibitor as adjuvant melanoma treatments in the development of novel therapeutic approaches