Biosimilar filgrastim vs filgrastim: a multicenter nationwide observational bioequivalence study in patients with chemotherapy-induced neutropenia

Background: We studied the comparative effectiveness of biosimilar filgrastim vs original filgrastim in patients with chemotherapy-induced neutropenia.Patients and methods: This multicenter, observational study was conducted at 14 centers. The study included 337 patients experiencing neutropenia under chemotherapy. Patients were given either filgrastim 30 MIU or 48 MIU (Neupogen (R)) or biosimilar filgrastim 30 MIU (Leucostim (R)). Data regarding age, chemotherapeutic agents used, number of chemotherapy courses, previous diagnosis of neutropenia, neutrophil count of patients after treatment, medications used for the treatment of neutropenia, and duration of neutropenia were collected. Time to absolute neutrophil count (ANC) recovery was the primary efficacy measure.Results: Ambulatory and hospitalized patients comprised 11.3% and 45.1% of the enrolled patients, respectively, and a previous diagnosis of neutropenia was reported in 49.3% of the patients, as well. Neutropenia occurred in 13.7% (n=41), 45.5% (n=136), 27.4% (n=82), 11.4% (n=34), and 2.0% (n=6) of the patients during the first, second, third, fourth, and fifth cycles of chemotherapy, respectively. While the mean neutrophil count was 0.53 +/- 0.48 before treatment, a significant increase to 2.44 +/- 0.66 was observed after treatment (p=0.0001). While 90.3% of patients had a neutrophil count,1.49 before treatment, all patients had a neutrophil count >= 1.50 after treatment. Neutropenia resolved within <= 4 days of filgrastim therapy in 60.1%, 56.7%, and 52.6% of the patients receiving biosimilar filgrastim 30 MIU, original filgrastim 30 MIU, and original filgrastim 48 MIU, respectively. However, there was no significant difference between the three arms (p=0.468). Similarly, time to ANC recovery was comparable between the treatment arms (p=0.332).Conclusion: The results indicate that original filgrastim and biosimilar filgrastim have comparable efficacy in treating neutropenia. Biosimilar filgrastim provides a valuable alternative; however, there is need for further studies comparing the two products in different patient subpopulations

A Survival Analysis of Islamic and Conventional Banks

Are Islamic banks inherently more stable than conventional banks? We address this question by applying a survival analysis based on the Cox proportional hazard model to a comprehensive sample of 421 banks in 20 Middle and Far Eastern countries from 1995 to 2010. By comparing the failure risk for both bank types, we find that Islamic banks have a significantly lower risk of failure than that of their conventional peers. This lower risk is based both unconditionally and conditionally on bank-specific (microeconomic) variables as well as macroeconomic and market structure variables. Our findings indicate that the design and implementation of early warning systems for bank failure should recognize the distinct risk profiles of the two bank types

From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways

The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut-brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies.GB Rogers, DJ Keating, RL Young, M-L Wong, J Licinio, and S Wesseling

Comparison of uroprotective efficacy of mesna and amifostine in Cyclophosphamide- induced hemorrhagic cystitis in rats

Background:Hemorrhagic cystitis (HC) is a dose limiting side effect of cyclophosphamide (CYP). AIM: In this study, we aimed to investigate the role of amifostine in the protection of CYP-induced HC and compare its efficacy with mesna. SETTING AND DESIGN: This animal study was conducted in the Experimental Animals Breeding and Research Center of the Medical Faculty of Uludag University. MATERIALS AND METHODS: Male Wistar rats (150-200 g; 10 rats per group) were randomly assigned to four groups. Group I (control group) received no drugs, group II received CYP (200 mg/kg, i.p.) alone, group III received amifostine (200 mg/kg, i.p.) and CYP, and group IV received CYP and mesna (40 mg/kg, i.p.) immediately and 4 and 8 h after administration of CYP. Bladders of animals were assessed macroscopically and histologically 24 h later. Gross assessment for presence of edema and hemorrhage and histological evaluation of damage to the bladder were scored according to Gray's criteria. STATISTICAL ANALYSIS USED: For macroscopic and microscopic data, we used statistical evaluation by Kruskal-Wallis nonparametric analysis of variance followed by the Mann-Whitney U-test. RESULTS: All the animals in group II had evidence of HC. Significant histological damage and macroscopic changes were present in this group compared to control group ( P &lt; 0.001). The median scores for bladder damage in group III and IV were significantly lower compared to group II ( P &lt; 0.001). When the median scores for bladder damage of group I, III, and IV were compared, there was no significant difference among these groups. CONCLUSION: This study demonstrated the efficacy of amifostine in prevention of cyclophosphamide-induced hemorrhagic cystitis

The evaluation of the protective effect of venlafaxine against chemotherapy induced neuropathy

Objective: Taxanes are widely used chemotherapeutic agents in the treatment of several malignancies including breast, non-small cell lung, ovarian and head and neck cancers. Toxicity of these agents includes bone marrow suppression (principally neutropenia), hypersensitivity reactions, cutaneous reactions, edema and neurotoxicity. Neurotoxicity develops cumulatively and is among the most important and dose limiting toxicity of these agents. The most prominent neurotoxicity is sensory neuropathy. The precise mechanism for taxane-induced neuropathy is still unknown. The taxanes are known to promote aggregation of intracellular microtubules. Abnormal aggregation of microtubules in the neuronal cells may cause this neuropathy. Recently, a novel antidepressant agent venlafaxine was reported to have a preventive role in the chemotherapy-induced neurotoxicity. In this study, we aimed to investigate the protective effect of venlafaxine against paclitaxel- and docetaxel-induced neurotoxicity while using it with paclitaxel and docetaxel. Material and Methods: Between January 2004 and September 2004 in the Department of Oncology, School of Medicine, Uludag University, 22 patients with solid tumors planned to receive paclitaxel or docetaxel based chemotherapy were enrolled in the study. 12 patients in group A were treated with chemotherapy alone while 10 patients in group B were treated with chemotherapy plus venlafaxine (75 mg/day). Total neuropathy scores (TNS) and pain scores (VAS) were determined for all patients before chemotherapy and after the last course of chemotherapy. Results: There was no statistically significant difference in terms of TNS and VAS scores between groups A and B. Conclusion: As a result, we decided that venlafaxine had no protective effect on neuropathy induced by taxane-dependent chemotherapy regimes. Copyright © 2008 by Türkiye Klinikleri