Evaluation of the cost saving potential of introducing Benepali® and Flixabi® on the European and Italian markets

INTRODUCTION: Biosimilar products play an important role in improving the access to biological medicines for an increased number of patients and enhancing the financial sustainability of the health systems.AIM: To assess the cost saving potential associated with the introduction of two biosimilars (Benepali® and Flixabi®) vs. their respective reference biological products on the European and Italian markets.METHODS: A budget impact model was developed to estimate the cost saving of the hypothetical introduction of Benepali® and Flixabi® vs. Enbrel® and Remicade®, respectively, in three European countries. The analysis was conducted from the payer perspective, over a 3-year period. In addition, the same model was used to assess the impact of Benepali® vs. Enbrel® in three Italian regions over a 2-year period. The model compares the costs associated with the current treatment patterns, used to manage patients with all the conditions which Benepali® and Flixabi® are authorized for, with that of a hypothetical treatment pattern in which biosimilar products have been introduced. Only direct costs associated with the drug acquisition were considered. The model was constructed using published country- or region-specific data, where available. Annual drug acquisition costs were calculated using the dosing information from SPCs and country-/region-specific price lists.RESULTS: The introduction of Benepali® and Flixabi® in the biologic therapeutic setting of three European countries resulted in substantial cost savings across the entire scenario, with different penetration over a 3-year period. Similarly, over a 2-year horizon, the introduction of Benepali® in the biologic therapeutic setting of three Italian regions resulted in significant cost savings. In all cases, the greater savings were observed in the scenario where the biosimilars’ penetration was higher.CONCLUSIONS: The introduction of Benepali® and Flixabi® has a substantial cost saving potential for the Italian and European health systems, and the budget impact is sensitive to the uptake rates of the biosimilars market

TRPV4 channels dominant role in the temperature modulation of intrinsic contractility and lymph flow of rat diaphragmatic lymphatics

The lymphatic system drains and propels lymph by extrinsic and intrinsic mechanisms. Intrinsic propulsion depends upon spontaneous rhythmic contractions of lymphatic muscles in the vessel walls, and is critically affected by changes in the surrounding tissue like osmolarity and temperature. Lymphatics of the diaphragm display a steep change in contraction frequency in response to changes in temperature, and this, in turn, affects lymph flow. In the present work we demonstrated, in an ex vivo diaphragmatic tissue rat model, that diaphragmatic lymphatics express transient receptor potential channels of the vanilloid 4 subfamily (TRPV4), and that their blockade by both the non-selective antagonist, Ruthenium Red and by the selective antagonist, HC-067047, abolished the response of lymphatics to temperature changes. Moreover, the selective activation of TRPV4 channels by means of GSK1016790A mirrored the behavior of vessels exposed to increasing temperatures, pointing out the critical role played by these channels in sensing the temperature of the lymphatic vessels environment and thus inducing a change in contraction frequency and lymph flow

Sobre pandemias e os direitos (de todos) animais

The health tragedy caused by a zoonosis, which has already killed more than 3 million people worldwide, highlights that talking about animal rights is essentially talking about human rights. The new coronavirus agent (COVID-19) urges us to recognize the interdependence of all living things, and leads us to reflect on the relationship between human and non-human animals. In light of the institutional purpose of the Center for Studies on Animal Rights and Intersectionality (NEDAI / CEAM / UnB), we will review the literature in order to identify the possible relationships between animal rights violations and the proliferation of pandemics that end up also victimizing human animals . We will move on to the history of the main pandemics already faced. We will discuss the programmed effects of the capitalist industry of animal production on the environment and the proliferation of diseases. And we are going to examine two moments when the violation of animal rights ends up turning against human animals, favoring the proliferation of pandemics: the intensive breeding of farm animals and the pet industry. As we will see, as a way of preserving themselves, human animals need to find a harmonious way of respecting the rights of non-human animals and nature.La tragedia sanitaria causada por una zoonosis, que ha matado a más de 3 millones de personas en todo el mundo, pone de manifiesto que hablar de los derechos de los animales es esencialmente hablar de los derechos humanos. El nuevo agente del coronavirus (COVID-19) nos impulsa a reconocer la interdependencia de todos los seres vivos, y nos lleva a reflexionar sobre la relación entre los animales humanos y no humanos. A la luz del propósito institucional del Centro de Estudios sobre Derechos Animales e Interseccionalidades (NEDAI/CEAM/UnB), haremos una revisión bibliográfica para identificar las posibles relaciones entre las violaciones de los derechos de los animales y la proliferación de pandemias que terminan victimizando también a los animales humanos. Discutiremos los efectos programados de la industria capitalista de producción animal sobre el medio ambiente y la proliferación de enfermedades. Y examinaremos dos momentos en los que la violación de los derechos de los animales acaba volviéndose contra los animales humanos, favoreciendo la proliferación de pandemias: la cría intensiva de animales de producción y la industria de los animales de compañía. Como veremos, como forma de preservarse, los animales humanos necesitan encontrar una forma armoniosa de respetar los derechos de los animales no humanos y de la naturaleza.A tragédia sanitária causada por uma zoonose, que já matou mais de 3 milhões de pessoas em todo o mundo, coloca em evidência que falar de direitos animais é essencialmente falar de direitos humanos. O novo agente do coronavírus (COVID-19) nos impele ao reconhecimento da interdependência de todas as coisas vivas, e nos leva a refletir sobre a relação entre animais humanos e não humanos. À luz do propósito institucional do Núcleo de Estudos sobre Direitos Animais e Interseccionalidades (NEDAI/CEAM/UnB), faremos uma revisão bibliográfica a fim de identificar as possíveis relações entre violações de direitos animais e a proliferação de pandemias que acabam vitimando também os animais humanos. Discutiremos os efeitos programados da indústria capitalista da produção animal no meio ambiente e proliferação de doenças. E vamos examinar dois momentos em que a violação dos direitos animais acaba se voltando contra os animais humanos, favorecendo a proliferação de pandemias: a criação intensiva de animais de produção e a indústria de animais de estimação. Conforme veremos, como forma de se auto preservar, os animais humanos precisam encontrar uma forma harmoniosa de respeitar os direitos dos não humanos e da natureza

Anxiety and Depression Prevalence Rates in Age-Related Macular Degeneration

PURPOSE. To estimate the prevalence rates of depression and anxiety in patients with wet age-related macular degeneration (AMD) and the relationship with visual acuity and to develop a simple algorithm for depression screening. METHODS. This cross-sectional, prospective, observational, multicenter study was performed in France, Germany, and Italy. Retina specialists at 10 centers per country each enrolled 12 consecutive patients with wet ARMD. Patients were stratified into four severity groups by using best eye (BE) and worst eye (WE) visual acuity (VA) thresholds (BE:VA 20/40 and WE:VA 20/200). Patients rated themselves on the Hospital Anxiety and Depression Scale (HADS). Analysis of variance was performed to estimate the effect of VA severity levels on HADS scores adjusted on age, gender, and country. RESULTS. Patients (females 609/6) were recruited, with a mean age of 77 years and 2.3 years' disease duration. Mean BE:VA at inclusion was 0.49 logMar (logarithm of the minimum angled of resolution) and NW:VA 1.0 logMar. The prevalence of severe depression increased from 0% (BE:VA >= 20/40+WE:VA >= 20/200) to 7.6% (BE:VA < 20/40+)WE:VA < 20/200), whereas anxiety was unrelated to VA loss. Moreover, total depression scores were strongly associated with VA severity (P = 0.006), but not total anxiety scores (P = 0.840). Responses to two HADS items ("I still enjoy things I used to enjoy"; "I can enjoy a good book or radio or television program") identified 95% of severely to moderately depressed patients. CONCLUSIONS. Self-rated depression in patients with AMD was associated with VA severity level. It should, therefore, be relatively easy for ophthalmologists to implement the screening procedure and refer identified patients to psychiatrists for proper assessment and treatment

Mutations in blind cavefish target the light-regulated circadian clock gene, period 2

Light represents the principal signal driving circadian clock entrainment. However, how light influences the evolution of the clock remains poorly understood. The cavefish Phreatichthys andruzzii represents a fascinating model to explore how evolution under extreme aphotic conditions shapes the circadian clock, since in this species the clock is unresponsive to light. We have previously demonstrated that loss-of-function mutations targeting non-visual opsins contribute in part to this blind clock phenotype. Here, we have compared orthologs of two core clock genes that play a key role in photic entrainment, cry1a and per2, in both zebrafish and P. andruzzii. We encountered aberrantly spliced variants for the P. andruzzii per2 transcript. The most abundant transcript encodes a truncated protein lacking the C-terminal Cry binding domain and incorporating an intronic, transposon-derived coding sequence. We demonstrate that the transposon insertion leads to a predominantly cytoplasmic localization of the cavefish Per2 protein in contrast to the zebrafish ortholog which is distributed in both the nucleus and cytoplasm. Thus, it seems that during evolution in complete darkness, the photic entrainment pathway of the circadian clock has been subject to mutation at multiple levels, extending from opsin photoreceptors to nuclear effectors.Universidad de Ferrara | Ref. FAR2014-201

Functionalization of PU Foams via Inorganic and Organic Coatings to Improve Cell and Tissue Interactions

In this work an innovative method to obtain hybrid bio-functional scaffolds has been developed. Polyether urethane (PU) foam scaffolds were synthetized by one-step gas foaming process. PU foams were coated with crosslinked gelatin hydrogel to promote cell adhesion and proliferation for the regeneration of soft tissues (e.g., adipose tissue). PU foams were coated with inorganic coating (i.e., CaPs) to improve the interaction with osteoblasts for bone tissue regeneration. The functionalized 3D PU porous scaffolds have been characterized investigating morphological properties by SEM and microCT, water uptake and coating stability, and compressive mechanical properties. Adipose tissue derived stem cells (ADSCs), endothelial cells (MS1), amnion mesenchymal cells (AMCs) and chorion mesenchymal cells (CMCs) isolated from human placenta were in vitro cultured on the hybrid functionalized 3D scaffolds. Mechanical properties showed elastic modulus ranging between 15.75 ± 2.14 and 22.9 ± 3.1 kPa; in vitro biological studies showed good cell adhesion, proliferation, and differentiation. In particular, compared to the results with uncoated PU, when cells where differentiated into adipocytes, Oil red O staining confirmed a higher presence of lipid droplets; in case of osteoblasts differentiation, inorganic extracellular matrix deposition was evidenced on CaPs coated PU. The obtained results suggest the important role of an adequate coating on the scaffold to stimulate a better interaction with cells, promoting the differentiation into different cells phenotypes

Impiego degli Inibitori della Pompa protonica (IPP) in Piemonte: indagine sulle abitudini prescrittive dei Medici di Medicina Generale

Proton Pump Inhibitors (PPIs) (Omeprazole, Lansoprazole, Pantoprazole, Rabeprazole and Esomeprazole), one of the most commonly prescribed classes of medications in the primary care setting, are considered a major advance in the treatment of acid-peptic diseases. In Italy PPIs are reimbursed by National Health Service on the basis of CUF (Commissione Unica del Farmaco) 1 and 48 Notes. In 2002 and 2003 a significant increase in PPIs consumption and expenditure have been documented, showing differences between regions. The aim of this study is to investigate and monitor, at regional level, type and entity of PPIs use through a drug utilization study, evaluating prescribing behaviour and compliance of PPIs treatments with CUF Notes indications. The study has been carried out on a sample of 436 General Practitioners belonging to 22 Piemonte's ASL (Aziende Sanitarie Locali). The data analysis shows that acid-related pathologies are significantly more common in patients with at least 50 years of age and the most frequent condition is represented by gastroesophageal reflux disease. Despite the general conditions of PPIs use by General Practitioners in terms of duration and dosage of therapy result in most cases (from 49% to 80% for duration and from 54% to 97% for dosage) compliant with what proposed by CUF Notes, in some cases the same CUF Notes indications seem to be not observed. Consequently the Piemonte Region has decided to plan a guideline on PPIs rational use. Such guideline, expected to be introduced in the regional area, may also be considered as an instrument able to lead to a more appropriate expenditure for this drug class. Moreover, in order to control PPIs expenditure, pharmacoeconomic methodologies can be applied allowing to identify the most cost - effective active substance and therapeutic scheme, overcoming CUF Notes which consider all PPIs use under the same reimbursement conditions