First-line HIV treatment: evaluation of backbone choice and its budget impact

OBJECTIVE: The gradual increase of persons living with HIV, mainly due to the reduced mortality achieved with effective antiretroviral therapies, calls for increased rationality and awareness in health resources consumption also during the early illness phases. Aim of this work is the estimation of the budget impact related to the variation in backbone prescribing trends in naïve patients.METHODS: Target population is the number of patients starting antiretroviral therapy each year, according to the Italian HIV surveillance registry, excluding patients receiving non-authorized or non-recommended regimens. We modeled 3-year mortality and durability rates on a dynamic cohort, basing on international literature. A prevalent patients analysis has also been conducted, for which the model is fed by a closed cohort consisting of all the patients without experience of virologic failure. The aim of this collateral analysis is to estimate the difference in current annual expenditures if the past prescription trends for patients starting therapy would have led to the evaluated hypothetical scenarios. Current Italian market shares of triple regimens containing first-choice or alternative backbones (tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine) are compared to three hypothetical scenarios (base-case, minimum and maximum) in which increasing shares of patients eligible to abacavir/lamivudine start first line treatment with this backbone. Annual cost for each regimen comprises drugs acquisition under hospital pricing rules, monitoring exams and preventive tests, valued basing on regional reimbursement tariffs.RESULTS: According to current prescribing trends, in the next three years about 13,000 patients starting HIV therapy will receive tenofovir/emtricitabine (83% of the target population), and minor portions other regimens (9% abacavir/lamivudine, 8% zidovudine/lamivudine). Patients that would be eligible to abacavir/lamivudine are 1.5, 4.5 and 6 thousand more than those presently treated according to the three hypothetical scenarios, leading to a cumulative saving of 850 thousand, 2.4 million and 3.3 million euro, respectively. If in the past the same modification of first line prescription trend was adopted, the annual current cost saving would vary from 922 thousands to 7.3 million euro. Most of this amount is due to reduced acquisition costs and, secondarily, to lower monitoring needs.CONCLUSION: Where patient features don't force the choice of the backbone, abacavir/lamivudine prescription may induce substantial savings, allowing the release of resources needed to manage more complicated/advanced cases

Integrating Health Technology Assessment and Multi-Criteria Decision Analysis in Optimizing Diabetic Macular Edema Management: Results from an Italian Multi-Regional Study

Health Technology Assessment (HTA) is a widely implemented technical tool used to inform the decision-making process..

La territorializzazione del farmaco in epoca di PNRR: prospettive, opportunità e spunti di riflessione da un panel di esperti

This document illustrates the results of the work of two interdisciplinary and multistakeholder panels (resear-chers, public institutions, and industry representatives) on drug territorialization and digitalization, organized as part of a residential seminar held on 30 September and 1st October 2021. Arising from some considerations about the demand for health and the provisions of the National Recovery and Resilience Plan (PNRR), the discussion touched various aspects of managing the transition from current to future management models. The importance of identifying criteria for prioritizing interventions in the area emerged: different methods of drug delivery, scientific information and measurement, re-evaluation of pathologies that can be managed in this area. Finally, the role of digitization within this change was explored. The opinions provided by the experts move towards making the most of the opportunities arising from PNRR, in terms of investments in healthcare and data application, with a view to improve health system efficiency, patient care and related outcomes

Uncoupling of p21 induction and MyoD activation results in the failure of irreversible cell cycle arrest in doxorubicin-treated myocytes

Doxorubicin (Dox, Adriamicin), a potent broad spectrum anthracycline anticancer drug, selectively inhibits muscle specific gene expression in cardiac cells in vivo and prevents terminal differentiation of skeletal muscle cells in vitro. By inducing the expression of the helix-loop-helix (HLH) transcriptional inhibitor ld2, Dox represses the myogenic function of the MyoD family of muscle regulatory factors (MRFs). In many cell types, terminal differentiation is coupled to an irreversible exit from the cell cycle and MyoD plays a critical role in the permanent cell cycle arrest of differentiating myocytes by upregulating the cyclin dependent kinase inhibitor (cdki) p21. Here, we correlate Dox effects on cell cycle with changes of E2F/DP complexes and activity in differentiating C2C12 myocytes. In Dox-treated quiescent myoblasts, which fail to differentiate into myotubes under permissive culture conditions, serum re-stimulation induces cyclin/cdk re-association on the E2F/DP complexes and this correlates with an evident increase in E2F/DP driven transcription and re-entry of myoblasts into the cell cycle. Despite Dox ability to activate the DNA-damage dependent p53/p21 pathway when induced in the absence of MyoD or other MRFs, p21 fails to maintain the postmitotic state in Dox-treated myocytes induced to differentiate. Thus, uncoupling p21 induction and MyoD activity results in a serum-reversible cell cycle arrest, indicating that MRF specific activation of cdki(s) is required for permanent cell cycle arrest in differentiating muscle cells. (C) 1997 Wiley-Liss, Inc

Mobile ticketing with NFC management for transport companies. Problems and solutions

In this paper we analyze the problems that are encountered in mobile ticketing systems where proximity technologies are used for validation and check of the e-tickets, leaving out the stage of ticket purchase, which can be done either remotely or in proximity. We have identified several security issues that are common in mobile ticketing and we propose some methods to solve them. In addition, we propose a protocol to provide secure validation and check of e-tickets. The innovation of this protocol is that it provides a good level of security and it is sufficiently abstract to be independent of NFC operating mode; that is it works in classical Card Emulation mode making use of Secure Element and it is implementable in Peer-to-Peer mode too

A Multi-Criteria Decision Analysis Approach within The Diabetic Macular Edema Field: The Experience of 3 Italian Regions

29 October-2 November 201

Burden of Moderate-to-Severe Plaque Psoriasis and New Therapeutic Approaches (Secukinumab): An Italian Perspective

<p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>. </b><a href="https://link.springer.com/article/10.1007/s13555-016-0114-9">https://link.springer.com/article/10.1007/s13555-016-0114-9</a></p><p></p> <p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p

Diabetic macular edema, innovative technologies and economic impact: new opportunities for the Lombardy Region healthcare system?

Purpose: Diabetic macular edema (DME) is a leading cause of vision loss and blindness. The aim of this study was to evaluate the economic benefits of introducing additional alternative technologies (Dexamethasone intravitreal implant - DEX - and Aflibercept injections), compared with the historical scenario of Ranibizumab intravitreal injections. Methods: A 3-year budget impact model was developed, taking into consideration the perspective of the Lombardy Region Healthcare Service (LRHS). Total administration costs (real-life data retrieved from clinical practice at three Departments of Ophthalmology) as well as costs related to the management of potential adverse events (information collected from the literature) were analysed. Results: Over a 36-month horizon, the results showed that a higher consumption of DEX could lead to significant economic savings for the Regional Healthcare Service, ranging from a minimum of -4.35% (if DEX were used only in the second-line of treatment) to a maximum of -12.97% (if DEX were used in both the first-line and second-line), including the potential impact of adverse events. Therapy costs with Aflibercept and Ranibizumab were similar. Conclusions: This study demonstrates that concentrating all eligible patients within the Ranibizumab regimen is unlikely to represent a cost-effective strategy. Indeed, significant economic advantages would be achieved by introducing the other licensed alternatives, Dexamethasone implant and Aflibercept, thus optimising DME Italian healthcare expenditure. The results demonstrate DEX as an advantageous technological alternative for the target population affected by DME, both as a first- and second-line treatment option, reducing the economic burden of the pathology for the Regional/National Health Service

MiR-34a Targeting of Notch Ligand Delta-Like 1 Impairs CD15+/CD133+ Tumor-Propagating Cells and Supports Neural Differentiation in Medulloblastoma

Background: Through negative regulation of gene expression, microRNAs (miRNAs) can function as oncosuppressors in cancers, and can themselves show altered expression in various tumor types. Here, we have investigated medulloblastoma tumors (MBs), which arise from an early impairment of developmental processes in the cerebellum, where Notch signaling is involved in many of the cell-fate-determining stages. Notch regulates a subset of MB cells that have stem-cell-like properties and can promote tumor growth. On the basis of this evidence, we hypothesized that miRNAs targeting the Notch pathway can regulate these phenomena, and can be used in anti-cancer therapies. Methodology/Principal Findings: In a screening of potential targets within Notch signaling, miR-34a was seen to be a regulator of the Notch pathway through its targeting of Notch ligand Delta-like 1 (Dll1). Down-regulation of Dll1 expression by miR-34a negatively regulates cell proliferation, and induces apoptosis and neural differentiation in MB cells. Using an inducible tetracycline on-off model of miR-34a expression, we show that in Daoy MB cells, Dll1 is the first target that is regulated in MB, as compared to the other targets analyzed here: Cyclin D1, cMyc and CDK4. MiR-34a expression negatively affects CD133+/CD15+ tumor-propagating cells, then we assay through reverse-phase proteomic arrays, Akt and Stat3 signaling hypo-phosphorylation. Adenoviruses carrying the precursor miR-34a induce neurogenesis of tumor spheres derived from a genetic animal model of MB (Patch1+/- p53-/-), thus providing further evidence that the miR-34a/Dll1 axis controls both autonomous and non autonomous signaling of Notch. In vivo, miR-34a overexpression carried by adenoviruses reduces tumor burden in cerebellum xenografts of athymic mice, thus demonstrating an anti-tumorigenic role of miR-34a in vivo. Conclusions/Significance: Despite advances in our understanding of the pathogenesis of MB, one-third of patients with MB remain incurable. Here, we show that stable nucleic-acid-lipid particles carrying mature miR-34a can target Dll1 in vitro and show equal effects to those of adenovirus miR-34a cell infection. Thus, this technology forms the basis for their therapeutic use for the delivery of miR-34a in brain-tumor treatment, with no signs of toxicity described to date in non-human primate trials