Climate Change Is Likely to Increase the Development Rate of Anthelmintic Resistance in Equine Cyathostomins in New Zealand

Climate change is likely to influence livestock production by increasing the prevalence of diseases, including parasites. The traditional practice of controlling nematodes in livestock by the application of anthelmintics is, however, increasingly compromised by the development of resistance to these drugs in parasite populations. This study used a previously developed simulation model of the entire equine cyathostomin lifecycle to investigate the effect a changing climate would have on the development of anthelmintic resistance. Climate data from six General Circulation Models based on four different Representative Concentration Pathways was available for three New Zealand locations. These projections were used to estimate the time resistance will take to develop in the middle (2040–49) and by the end (2090–99) of the century in relation to current (2006–15) conditions under two treatment scenarios of either two or six yearly whole-herd anthelmintic treatments. To facilitate comparison, a scenario without any treatments was included as a baseline. In addition, the size of the infective and parasitic stage nematode population during the third simulation year were estimated. The development of resistance varied between locations, time periods and anthelmintic treatment strategies. In general, the simulations indicated a more rapid development of resistance under future climates coinciding with an increase in the numbers of infective larvae on pasture and encysted parasitic stages. This was especially obvious when climate changes resulted in a longer period suitable for development of free-living parasite stages. A longer period suitable for larval development resulted in an increase in the average size of the parasite population with a larger contribution from eggs passed by resistant worms surviving the anthelmintic treatments. It is projected that climate change will decrease the ability to control livestock parasites by means of anthelmintic treatments and non-drug related strategies will become increasingly important for sustainable parasite control

The worldwide clinical trial research response to the COVID-19 pandemic - the first 100 days

Background: Never before have clinical trials drawn as much public attention as those testing interventions for COVID-19. We aimed to describe the worldwide COVID-19 clinical research response and its evolution over the first 100 days of the pandemic. Methods: Descriptive analysis of planned, ongoing or completed trials by April 9, 2020 testing any intervention to treat or prevent COVID-19, systematically identified in trial registries, preprint servers, and literature databases. A survey was conducted of all trials to assess their recruitment status up to July 6, 2020. Results: Most of the 689 trials (overall target sample size 396,366) were small (median sample size 120; interquartile range [IQR] 60-300) but randomized (75.8%; n=522) and were often conducted in China (51.1%; n=352) or the USA (11%; n=76). 525 trials (76.2%) planned to include 155,571 hospitalized patients, and 25 (3.6%) planned to include 96,821 health-care workers. Treatments were evaluated in 607 trials (88.1%), frequently antivirals (n=144) or antimalarials (n=112); 78 trials (11.3%) focused on prevention, including 14 vaccine trials. No trial investigated social distancing. Interventions tested in 11 trials with >5,000 participants were also tested in 169 smaller trials (median sample size 273; IQR 90-700). Hydroxychloroquine alone was investigated in 110 trials. While 414 trials (60.0%) expected completion in 2020, only 35 trials (4.1%; 3,071 participants) were completed by July 6. Of 112 trials with detailed recruitment information, 55 had recruited <20% of the targeted sample; 27 between 20-50%; and 30 over 50% (median 14.8% [IQR 2.0-62.0%]). Conclusions: The size and speed of the COVID-19 clinical trials agenda is unprecedented. However, most trials were small investigating a small fraction of treatment options. The feasibility of this research agenda is questionable, and many trials may end in futility, wasting research resources. Much better coordination is needed to respond to global health threats

Three-year study to evaluate an anthelmintic treatment regimen with reduced treatment frequency in horses on two study sites in Belgium

In the present study, an anthelmintic treatment regimen with reduced treatment frequency was evaluated in horses on two study sites in Belgium during three consecutive summer pasture seasons. Historically, the horses on both study sites were treated up to 6 times a year with ivermectin (IVM) or up to 4 times a year with moxidectin (MOX), and previous efficacy evaluations indicated a reduced egg reappearance period in some of the treated horses for both IVM (28 days) and MOX (42 days). In the present study, all horses were treated with IVM or MOX in the spring and in autumn. Faecal egg counts (FEC) were conducted every two weeks during the summer pasture season and whenever the individual FEC exceeded 250 eggs per gram of faeces, the specific horse was treated with pyrantel embonate. No increase in parasitic disease over the three-year period of the study was observed. The FEC data collected in the study as well as the age of the animals and local weather data were then imported into a cyathostomin life-cycle model, to evaluate long term effects of the newly applied treatment regimen on the selection pressure for anthelmintic resistance, and compare to the previous high frequency treatment regimen. The model simulations indicated that the whole-herd treatment regimen with at least 4 macrocyclic lactone treatments annually led 2-3 times faster resistance development than any of the alternative treatment regimens evaluated under the specific conditions of these two study sites. Further lowering the treatment frequency or applying even more selective treatments enhanced the delay in resistance development, but to a lesser extent

Pricing of oral generic cancer medicines in 25 European countries; findings and implications

Introduction: There are appreciable concerns among European health authorities with growing expenditure on cancer medicines and issues of sustainability. The enhanced use of low-cost generics could help. Aims: Consequently, there is a need to comprehensively document current and future arrangements regarding the pricing of generic cancer medicines across Europe, and whether these are indication specific, as well as how this translates into actual prices to provide future direction. Methodology: Mixed-method approach with qualitative research among senior health authority personnel and their advisers. Quantitative research via health authority databases to ascertain current prices for oral cancer medicines that had lost their patent and the influence of population size and economics on prices. Results: Twenty-five European countries participated. The research found the following issues: (a) variable approaches to the pricing of generic cancer medicines, which will continue; (b) no concerns with substitution for oral generic cancer medicines; (c) substantial price reductions versus originators for generic capecitabine (up to -93.1%), generic imatinib (up to -97.8%) and generic temozolomide (up to -80.7%). Prices for oncology medicines are not generally indication specific, and are not affected by population size although influenced by pricing approaches. There have also been price increases for some non-patented cancer medicines following manufacturer changes although now stabilizing. Conclusion: The considerable price reductions seen for some generics means health authorities should further encourage the use of generic oncology medicines when they become available to fund increased volumes and new valued cancer medicines. Countries are also starting to address price increases for generics following changes in the manufacturer

The Role of University Scientist Mobility for Industrial Innovation

Scientific knowledge is an important ingredient in the innovation process. Drawing on the knowledge-based view of the firm and the literature on the relationship between science and technology, this paper scrutinizes the importance of university scientists’ mobility for firms’ innovative activities. Combining patent data and matched employer-employee data for Danish firms, we can track the labor mobility of R&D workers from 1999 to 2004. We find that new joiners contribute more than long-term employees to innovative activity in the focal firm. Among new firm recruits, we observe that newly hired former university researchers contribute more to innovative activity than newly hired recent graduates or joiners from firms, but only in firms with a high level of absorptive capacity in the form of recent experience of hiring university researchers. We find also that firms’ recent experience of hiring university researchers enhances the effect of newly hired recent graduates’ contributions to innovation