Widening Consumer Access to Medicines through Switching Medicines to Non-Prescription: A Six Country Comparison

Background: Switching or reclassifying medicines with established safety profiles from prescription to non-prescription aims to increase timely consumer access to medicines, reduce under-treatment and enhance self-management. However, risks include suboptimal therapy and adverse effects. With a long-standing government policy supporting switching or reclassifying medicines from prescription to non-prescription, the United Kingdom is believed to lead the world in switch, but evidence for this is inconclusive. Interest in switching medicines for certain long-term conditions has arisen in the United Kingdom, United States, and Europe, but such switches have been contentious. The objective of this study was then to provide a comprehensive comparison of progress in switch for medicines across six developed countries: the United States; the United Kingdom; Australia; Japan; the Netherlands; and New Zealand. Methods: A list of prescription-to-non-prescription medicine switches was systematically compiled. Three measures were used to compare switch activity across the countries: ‘‘progressive’’ switches from 2003 to 2013 (indicating incremental consumer benefit over current non-prescription medicines); ‘‘first-in-world’’ switches from 2003 to 2013; and switch date comparisons for selected medicines.Results: New Zealand was the most active in progressive switches from 2003 to 2013, with the United Kingdom and Japan not far behind. The United States, Australia and the Netherlands showed the least activity in this period. Few medicines for long-term conditions were switched, even in the United Kingdom and New Zealand where first-in-world switches were most likely. Switch of certain medicines took considerably longer in some countries than others. For example, a consumer in the United Kingdom could self-medicate with a non-sedating antihistamine 19 years earlier than a consumer in the United States. Conclusion: Proactivity in medicines switching, most notably in New Zealand and the United Kingdom, questions missed opportunities to enhance consumers’ self-management in countries such as the United States

Prompt atmospheric neutrino fluxes: perturbative QCD models and nuclear effects

We evaluate the prompt atmospheric neutrino flux at high energies using three different frameworks for calculating the heavy quark production cross section in QCD: NLO perturbative QCD, $k_T$ factorization including low-$x$ resummation, and the dipole model including parton saturation. We use QCD parameters, the value for the charm quark mass and the range for the factorization and renormalization scales that provide the best description of the total charm cross section measured at fixed target experiments, at RHIC and at LHC. Using these parameters we calculate differential cross sections for charm and bottom production and compare with the latest data on forward charm meson production from LHCb at $7$ TeV and at $13$ TeV, finding good agreement with the data. In addition, we investigate the role of nuclear shadowing by including nuclear parton distribution functions (PDF) for the target air nucleus using two different nuclear PDF schemes. Depending on the scheme used, we find the reduction of the flux due to nuclear effects varies from $10\%$ to $50 \%$ at the highest energies. Finally, we compare our results with the IceCube limit on the prompt neutrino flux, which is already providing valuable information about some of the QCD models.Comment: 61 pages, 25 figures, 11 table

SFCOMPO 2.0 – A relational database of spent fuel isotopic measurements, reactor operational histories, and design data

SFCOMPO-2.0 is a database of experimental isotopic concentrations measured in destructive radiochemical analysis of spent nuclear fuel (SNF) samples. The database includes corresponding design description of the fuel rods and assemblies, relevant operating conditions and characteristics of the host reactors necessary for modelling and simulation. Aimed at establishing a thorough, reliable, and publicly available resource for code and data validation of safety-related applications, SFCOMPO-2.0 is developed and maintained by the OECD Nuclear Energy Agency (NEA). The SFCOMPO-2.0 database is a Java application which is downloadable from the NEA website

Comparison of model predictions of typhoid conjugate vaccine public health impact and cost-effectiveness

Models are useful to inform policy decisions on typhoid conjugate vaccine (TCV) deployment in endemic settings. However, methodological choices can influence model-predicted outcomes. To provide robust estimates for the potential public health impact of TCVs that account for structural model differences, we compared four dynamic and one static mathematical model of typhoid transmission and vaccine impact. All models were fitted to a common dataset of age-specific typhoid fever cases in Kolkata, India. We evaluated three TCV strategies: no vaccination, routine vaccination at 9 months of age, and routine vaccination at 9 months with a one-time catch-up campaign (ages 9 months to 15 years). The primary outcome was the predicted percent reduction in symptomatic typhoid cases over 10 years after vaccine introduction. For three models with economic analyses (Models A-C), we also compared the incremental cost-effectiveness ratios (ICERs), calculated as the incremental cost (US$) per disability-adjusted life-year (DALY) averted. Routine vaccination was predicted to reduce symptomatic cases by 10-46$95-789 per DALY averted; two models predicted the ICER of routine vaccination alone to be greater than with the addition of catch-up campaign. Despite differences in model-predicted vaccine impact and cost-effectiveness, routine vaccination plus a catch-up campaign is likely to be impactful and cost-effective in high incidence settings such as Kolkata

Spatial and genomic data to characterize endemic typhoid transmission

BACKGROUND: Diverse environmental exposures and risk factors have been implicated in the transmission of Salmonella Typhi, however, the dominant transmission pathways through the environment to susceptible humans remain unknown. Here, we utilize spatial, bacterial genomic, and hydrological data to refine our view of Typhoid transmission in an endemic setting. METHODS: 546 patients presenting to Queen Elizabeth Central Hospital in Blantyre, Malawi with blood culture-confirmed typhoid fever between April 2015 and January 2017 were recruited to a cohort study. The households of a subset of these patients were geolocated, and 256 S. Typhi isolates were whole genome sequenced. Pairwise single nucleotide variant (SNV) distances were incorporated into a geostatistical modeling framework using multidimensional scaling. RESULTS: Typhoid fever was not evenly distributed across Blantyre, with estimated minimum incidence ranging across the city from less than 15 to over 100 cases/100,000/year. Pairwise SNV distance and physical household distances were significantly correlated (p=0.001). We evaluated the ability of river catchment to explain the spatial patterns of genomics observed, finding that it significantly improved the fit of the model (p=0.003). We also found spatial correlation at a smaller spatial scale, of households living <192 meters apart. CONCLUSIONS: These findings reinforce the emerging view that hydrological systems play a key role in the transmission of typhoid fever. By combining genomic and spatial data, we show how multi-faceted data can be used to identify high incidence areas, understand the connections between them, and inform targeted environmental surveillance, all of which will be critical to shape local and regional typhoid control strategies

A Parasitoid Wasp Induces Overwintering Behaviour in Its Spider Host

Parasites and parasitoids control behaviors of their hosts. However, the origin of the behavior evoked by the parasitic organism has been rarely identified. It is also not known whether the manipulation is universal or host-specific. Polysphinctine wasps, koinobiont ectoparasitoids of several spider species that manipulate host web-spinning activity for their own protection during pupation, provide an ideal system to reveal the origin of the evoked behavior. Larva of Zatypota percontatoria performed species-specific manipulation of theridiid spiders, Neottiura bimaculata and Theridion varians, shortly before pupation. Parasitized N. bimaculata produced a dense web, whereas parasitized T. varians built a cupola-like structure. The larva pupated inside of either the dense web or the cupola-like structure. We discovered that unparasitized N. bimaculata produce an analogous dense web around their eggsacs and for themselves during winter, while T. varians construct an analogous ‘cupola’ only for overwintering. We induced analogous manipulation in unparasitized hosts by altering ambient conditions. We discovered that the behavior evoked by larvae in two hosts was functionally similar. The larva evoked protective behaviors that occur in unparasitized hosts only during specific life-history periods