Evaluation of an Oxide Layer on NI-CR-MO-W Alloy Using Electrochemical Impedance Spectroscopy and Surface Analysis

High corrosion resistance under very aggressive conditions is a distinguishing property of Ni-Cr-Mo-W alloys. One such alloy, Alloy 22, is a candidate material for fabrication of the outer layer of high-level nuclear waste (HLNW) packages for the proposed HLNW repository at Yucca Mountain, Nevada, USA. We are using Electrochemical Impedance Spectroscopy (EIS), ex-situ X-Ray Photoelectron Spectroscopy (XPS) and Time of Flight Secondary Ion Mass Spectroscopy (ToF SIMS) to characterize the electrochemical properties and composition of the protective oxide formed on Alloy 22 surfaces. These studies have been conducted at temperatures up to 90 C at potentials from -0.8 V to 0.8 V (vs. Ag/AgCl (sat'd KCl)) in deaerated 5 mol L{sup -1} NaCl solution. Using this combination of techniques, we can correlate the electrical (from EIS) and compositional properties (from XPS, ToF SIMS) of the oxide. At more negative potentials (-0.8 V to -0.4 V) the film exhibits a low charge transfer resistance and high capacitance, indicating the presence of a very defective film with a high concentration of electronic defects. The presence of additional elements in the equivalent circuit, corresponding to water reduction, supports this suggestion. At these potentials, surface analysis techniques show a thin oxide layer with a low concentration of Cr203. Increasing the potential (to between -0.2 and 0.2 V) leads to a major increase in overall interfacial resistance consistent with the formation of an oxide with a small concentration of electronic defects. At the same time, the surface analysis techniques show increases in the film thickness and the Cr{sub 2}O{sub 3} content. A further increase in potential to 0.8 V, in general, leads to a decrease in interfacial resistance throughout the film. When the Cr{sub 2}O{sub 3} barrier layer is degraded, then the higher oxidation states of Mo and W species (MO{sup VI}, W{sup VI}) increase in concentration and are stored in the outer part of the film (at temperatures up to 60 C). The storage of these high oxidation state ions generates a high interfacial capacitance. At high temperature (above 60 C), the XPS and EIS show that the high oxidation states of Mo and W are absent. We think this is because they dissolve from the oxide under those conditions

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

Ongoing strategies to improve the management of upper respiratory tract infections and reduce inappropriate antibiotic use particularly among lower and middle-income countries: findings and implications for the future

Introduction: Antibiotics are indispensable to maintaining human health; however, their overuse has resulted in resistant organisms, increasing morbidity, mortality and costs. Increasing antimicrobial resistance (AMR) is a major public health threat, resulting in multiple campaigns across countries to improve appropriate antimicrobial use. This includes addressing the overuse of antimicrobials for self-limiting infections, such as upper respiratory tract infections (URTIs), particularly in lower- and middle-income countries (LMICs) where there is the greatest inappropriate use and where antibiotic utilization has increased the most in recent years. Consequently, there is a need to document current practices and successful initiatives in LMICs to improve future antimicrobial use. Methodology: Documentation of current epidemiology and management of URTIs, particularly in LMICs, as well as campaigns to improve future antimicrobial use and their influence where known. Results: Much concern remains regarding the prescribing and dispensing of antibiotics for URTIs among LMICs. This includes considerable self-purchasing, up to 100% of pharmacies in some LMICs. However, multiple activities are now ongoing to improve future use. These incorporate educational initiatives among all key stakeholder groups, as well as legislation and other activities to reduce self-purchasing as part of National Action Plans (NAPs). Further activities are still needed however. These include increased physician and pharmacist education, starting in medical and pharmacy schools; greater monitoring of prescribing and dispensing practices, including the development of pertinent quality indicators; and targeted patient information and health education campaigns. It is recognized that such activities are more challenging in LMICs given more limited resources and a lack of healthcare professionals. Conclusion: Initiatives will grow across LMICs to reduce inappropriate prescribing and dispensing of antimicrobials for URTIs as part of NAPs and other activities, and these will be monitored

Variation in the prices of oncology medicines across Europe and the implications for the future

Introduction/ Objectives: There are increasing concerns among health authorities regarding the sustainability of healthcare systems with growing expenditure on medicines including new high-priced oncology medicines. Medicine prices among European countries may be adversely affected by their population size and economic power to negotiate. There are also concerns that prices of patented medicines do not change once the prices of medicines used for negotiations substantially change. This needs to be investigated as part of the implications of low-cost generic oncology medicines. Methodology: Analysing principally reimbursed prices of patented oral oncology medicines (imatinib, erlotinib and fludarabine) between 2013 and 2017 across Europe and exploring correlations between GDP, population size, and prices. Comparing the findings with previous research regarding prices of oral generic oncology medicines. Results: The prices of imatinib, erlotinib and fludarabine did vary among European countries but showed limited price erosion over time in the absence of generics. There appeared to be no correlation between population size and prices. However, higher prices were seen among countries with higher GDP per capita which is a concern for lower income countries referencing these. Discussion and Conclusion: It is likely that the limited price erosion for patented oncology medicines will change across Europe with increased scrutiny over their prices and value as more medicines used for pricing decisions lose their patents combined with growing pressures on the oncology drug budget. In addition, discussions will continue regarding fair pricing for new oncology medicines and other approaches given ever rising prices with research showing substantial price reductions for oral oncology medicines (up to -97.8% for imatinib) once generics become available. We are also seeing appreciable price reductions for biosimilars further increasing the likelihood of these developments

Barriers for Access to New Medicines: Searching for the Balance Between Rising Costs and Limited Budgets

Introduction: There is continued unmet medical need for new medicines across countries especially for cancer, immunological diseases and orphan diseases. However, there are growing challenges with funding new medicines at ever increasing prices along with funding increased medicine volumes with the growing prevalence of both infectious diseases and non-communicable diseases across countries. This has resulted in the development of new models to better manage the entry of new medicines, new financial models being postulated as well as strategies to improve prescribing efficiency. However, more needs to be done. Consequently, the primary aim of this paper is to consider potential ways to optimise the use of new medicines balancing rising costs with increasing budgetary pressures to stimulate debate especially from a payer perspective. Methods: A narrative review of pharmaceutical policies and implications, as well as possible developments, based on key publications and initiatives known to the co-authors principally from a health authority perspective. Results: A number of initiatives and approaches have been identified including new models to better manage the entry of new medicines based on three pillars (pre-, peri-, and post-launch activities). Within this, we see the growing role of horizon scanning activities starting up to 36 months before launch, managed entry agreements and post launch follow-up. It is also likely there will be greater scrutiny over the effectiveness and value of new cancer medicines given ever increasing prices. This could include establishing minimum effectiveness targets for premium pricing along with re-evaluating prices as more medicines for cancer lose their patent. There will also be a greater involvement of patients especially with orphan diseases. New initiatives could include a greater role of multicriteria decision analysis, as well as looking at the potential for de-linking research and development from commercial activities to enhance affordability. Conclusion: There are a number of ongoing activities across countries to try and fund new valued medicines whilst attaining or maintaining universal healthcare. Such activities will grow with increasing resource pressures and continued unmet need

Crevice Corrosion on Ni-Cr-Mo Alloys

Ni-Cr-Mo alloys were developed for their exceptional corrosion resistance in a variety of extreme corrosive environments. An alloy from this series, Alloy-22, has been selected as the reference material for the fabrication of nuclear waste containers in the proposed Yucca Mountain repository located in Nevada (US). A possible localized corrosion process under the anticipated conditions at this location is crevice corrosion. therefore, it is necessary to assess how this process may, or may not, propagate if the use of this alloy is to be justified. Consequently, the primary objective is the development of a crevice corrosion damage function that can be used to assess the evolution of material penetration rates. They have been using various electrochemical methods such as potentiostatic, galvanostatic and galvanic coupling techniques. Corrosion damage patterns have been investigated using surface analysis techniques such as scanning electron microscopy (SEM) and optical microscopy. All crevice corrosion experiments were performed at 120 C in 5M NaCl solution. Initiating crevice corrosion on these alloys has proven to be difficult; therefore, they have forced it to occur under either potentiostatic or galvanostatic conditions