The Implementation of Managed Entry Agreements in Central and Eastern Europe : Findings and Implications

Funding Information: In Bosnia and Herzegovina, both The Federation of Bosnia and Herzegovina and the Republic of Srpska, also have special funds and budgets in place for the financing of expensive medicines, which are innovative and under patent. Similar earmarked funds are available in Scotland (the New Medicines Fund funded by the Pharmaceutical Price Regulation Scheme [PPRS] rebates) [35] and England (the Cancer Drugs Fund) [36]. However, support for such earmarked funds is mixed. While they facilitate access, critics raised issues about fairness towards other disease areas and patient groups that are not eligible for special funding [3, 39]. Further, the views of a Patient and Clinician Engagement meeting in Scotland [37] and the end-of-life criteria in England [38] offer opportunities for special considerations affecting medicines for end-of-life and very rare conditions to be taken into account in the health technology assessment process. Funding Information: The authors would like to acknowledge Dr. Jan Jones from the Scottish Medicines Consortium, Scotland, for contributing to the discussion with information on Scotland, Drs. Lyudmila Bezmelnitsyna and Anastasia Isaeva for contributing to data collection in Russia and Dr. Kate?ina Podrazilov? from SZP ?R for providing information on the Czech Republic. Alessandra Ferrario was a Research Officer at the LSE Health at the time this research was conducted. She is now a postdoctoral Research Fellow at the Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, USA. Email: [email protected] No sources of funding were used for this study. The authors declare they have no conflicts of interest. However, Di?na Ar?ja, Maria Dimitrova, Jurij F?rst, Ieva Grei?i?t?-Kuprijanov, Iris Hoxha, Arianit Jakupi, Erki Laidm?e, Vanda Markovic-Pekovic, Dmitry Meshkov, Guenka Petrova, Maciej Pomorski and Patricia Vella Bonanno work directly for national health authorities or are advisers to them. Alessandra Ferrario, Tomasz Bochenek, Ileana Mardare, Dominik Tomek, Luka Voncina, Alan Haycox, Panos Kanavos,?Olga L?blov?, and Brian Godman are academics and independent researchers also working with national and regional health authorities and others to improve the quality and efficiency of prescribing, and Tarik Catic, D?vid Dank?,and Tanja Novakovic are involved with pharmaceutical, pharmacoeconomics and outcomes research groups in their countries. Olga L?blov? has also carried out remunerated consultancy activities for A&R Partners, Baxter AG and Instytut Arcana and Ileana Mardare has signed a consulting contract with Ewopharma A.G. Romania. The content of the paper and the conclusions are those of each author and may not necessarily reflect those of any organisation that employs them. Publisher Copyright: © 2017, The Author(s).Background: Managed entry agreements (MEAs) are a set of instruments to facilitate access to new medicines. This study surveyed the implementation of MEAs in Central and Eastern Europe (CEE) where limited comparative information is currently available. Method: We conducted a survey on the implementation of MEAs in CEE between January and March 2017. Results: Sixteen countries participated in this study. Across five countries with available data on the number of different MEA instruments implemented, the most common MEAs implemented were confidential discounts (n = 495, 73%), followed by paybacks (n = 92, 14%), price-volume agreements (n = 37, 5%), free doses (n = 25, 4%), bundle and other agreements (n = 19, 3%), and payment by result (n = 10, >1%). Across seven countries with data on MEAs by therapeutic group, the highest number of brand names associated with one or more MEA instruments belonged to the Anatomical Therapeutic Chemical (ATC)-L group, antineoplastic and immunomodulating agents (n = 201, 31%). The second most frequent therapeutic group for MEA implementation was ATC-A, alimentary tract and metabolism (n = 87, 13%), followed by medicines for neurological conditions (n = 83, 13%). Conclusions: Experience in implementing MEAs varied substantially across the region and there is considerable scope for greater transparency, sharing experiences and mutual learning. European citizens, authorities and industry should ask themselves whether, within publicly funded health systems, confidential discounts can still be tolerated, particularly when it is not clear which country and party they are really benefiting. Furthermore, if MEAs are to improve access, countries should establish clear objectives for their implementation and a monitoring framework to measure their performance, as well as the burden of implementation.publishersversionPeer reviewe

Integracja generacji rozproszonej z lokalnym zapotrzebowaniem w ramach lokalnego obszaru bilansowania

Intensive development of distributed generation, apart from the positive aspects related to the use of renewable energy, is also a challenge in terms of safety and reliability of energy supply. Ensuring the reliability of supplies, at the variable operation of wind generation and photovoltaic generation, requires from the network operators implement additional costly investments. An alternative solution is to build a system that integrates management of local energy resources (including automatic grid controls, energy storage, local energy sources) in order to optimize the technical possibilities of the grid.Intensywny rozwój generacji rozproszonej, oprócz pozytywnych aspektów związanych z wykorzystaniem energii odnawialnej, stanowi wyzwanie z punktu widzenia bezpieczeństwa i funkcjonowania Krajowego Systemu Elektroenergetycznego (KSE). Zapewnienie niezawodności dostaw, przy zmiennym charakterze pracy generacji wiatrowej i fotowoltaicznej, wymusza na operatorach sieci konieczność realizacji dodatkowych kosztownych inwestycji sieciowych. Alternatywnym rozwiązaniem jest budowa systemu umożliwiającego zintegrowane zarządzanie lokalnymi zasobami energetycznymi (m.in. automatyką sieciową, magazynami energii, lokalnymi źródłami energii) w celu optymalizacji technicznych możliwości sieci elektroenergetycznej

Toward a magic or imaginary bullet? Ligands for drug targeting to cancer cells: principles, hopes, and challenges

Monika Toporkiewicz, Justyna Meissner, Lucyna Matusewicz, Aleksander Czogalla, Aleksander F SikorskiLaboratory of Cytobiochemistry, Faculty of Biotechnology, University of Wrocław, Wrocław, PolandAbstract: There are many problems directly correlated with the systemic administration of drugs and how they reach their target site. Targeting promises to be a hopeful strategy as an improved means of drug delivery, with reduced toxicity and minimal adverse side effects. Targeting exploits the high affinity of cell-surface-targeted ligands, either directly or as carriers for a drug, for specific retention and uptake by the targeted diseased cells. One of the most important parameters which should be taken into consideration in the selection of an appropriate ligand for targeting is the binding affinity (KD). In this review we focus on the importance of binding affinities of monoclonal antibodies, antibody derivatives, peptides, aptamers, DARPins, and small targeting molecules in the process of selection of the most suitable ligand for targeting of nanoparticles. In order to provide a critical comparison between these various options, we have also assessed each technology format across a range of parameters such as molecular size, immunogenicity, costs of production, clinical profiles, and examples of the level of selectivity and toxicity of each. Wherever possible, we have also assessed how incorporating such a targeted approach compares with, or is superior to, original treatments.Keywords: targeting, drug delivery, tumor, monoclonal antibody, EGFR, cance

Two-dimensional correlation analysis of Raman optical activity data on the α-helix-to-β-sheet transition in poly(L-lysine)

Raman optical activity (ROA) has evolved into an incisive probe of structure and conformational transitions in polypeptides and proteins revealing many signal patterns characteristic of specific secondary structural elements. In order to further facilitate analysis of ROA spectral intensity variations, two-dimensional correlation methods are applied to ROA and Raman spectra monitoring the α-helix-to-β-sheet transition in poly(L-lysine) as a function of temperature. Pretreatment of data using background subtraction, normalization and gentle smoothing is essential for the successful generation of 2D ROA correlations, 2D Raman correlations and 2D Raman/ROA heterocorrelations. The pseudoscalar nature of ROA spectra results in detailed 2D correlation analyses providing extensive interpretation of spectral intensity variations. Synchronous plots indicate band assignments consistent with established assignments in poly(L-lysine) together with possible new assignments. Corresponding asynchronous plots probe the temporal sequence of the conformational transition indicating distinct temporal phases while monitoring aggregation through a small amount of β-structure present at the start of the experiment ahead of α-helix unfolding. This study demonstrates the potential of 2D correlation analysis as a valuable technique for the extraction of detailed information about aggregation and conformational transitions in polypeptides and proteins from associated ROA and Raman spectra. Results indicate that aggregation of poly(L-lysine) monomers precedes intramolecular conversion of α-helix to β-sheet, which is then followed by fibril formation

Two Novel Spectroscopic Techniques: 2D ROA and 2D Raman/ROA

No abstract available

Two Novel Spectroscopic Techniques: 2D ROA and 2D Raman/ROA

No abstract available

Wykorzystanie hydrozelu jonitowego Biona 111 jako podloza ogrodniczego

Badany hydrożel jonitowy został uzyskany w Instytucie Chemii Fizycznej i Organicznej Biało niskiej Akademii Nauk w Mińsku. Ocenę wykorzystania w/w sorbentu, jako podłoża do upraw ogrodniczych przeprowadzono w Katedrze Fizjologii Roślin AR w Lublinie. W doświadczeniu zastosowano następujące warianty: BIONA 111 w formie standardowej lub sproszkowanej, BIONA jako dodatek do gleby ogrodowej lub torfu torfowiska wysokiego w ilości 0,25: 0,50; 0,75 % obj. Celem było określenie wpływu tych podłoży na wschody, tempo wzrostu, zużycie wody i plonowanie kukurydzy cukrowej. Wykazano, że standardowa forma badanego substratu jest dobrym podłożem do upraw, warunkującym uzyskanie wysokich plonów przy znacznie mniejszym użyciu wody niż w warunkach gleby naturalnej. Wzbogacenie gleby w formę standardową badanego hydrożelu wpłynęło na proporcjonalny wzrost plonu do ilości dodanego substratu. Sproszkowany substrat stosowany jako podłoże lub jako dodatek do gleby, wyraźnie przyspieszał wschody, a uzyskane plony były proporcjonalne.Parallel investigation of fertility of standard garden soil with ion exchange substrate BIONA 111, as well as mixtures in different proportions has been done. The ion exchange substrate was a mixture of ion exchange resins saturated in certain proportions with the complete set of biogenic ions. It has been shown that the productivity of the ion exchange substrate in a 6 week vegetation period was 900 g of the green biomass as compared to 30 g per kilogram of the dry substrate. The productivity linearly depends on the mass fraction of the ion exchange substrate in the mixtures with the garden soil. As follows from this dependence addition of 1 % of the ion exchange substrate to completely depleted soil, barren sand is sufficient for starting vegetation. Addition of different ionic forms of ion exchange resin (K⁺, Ca²⁺ + Mg²⁺ + K⁺, NO₃⁻, NO₃⁻ + H₂PO₄²⁻ + SO₄²⁻ ) causes pronounced positive effects on soil productivity though less significant than those of the ion exchange substrate. It has been shown that addition of the ion exchange substrates can be an efficiant means for remediation of destroyed soils and fruitless rocks