Significant increase in azithromycin "resistance" and susceptibility to ceftriaxone and cefixime in Neisseria gonorrhoeae isolates in 26 European countries, 2019.

BACKGROUND: The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) performs annual sentinel surveillance of Neisseria gonorrhoeae susceptibility to therapeutically relevant antimicrobials across the European Union/European Economic Area (EU/EEA). We present the Euro-GASP results from 2019 (26 countries), linked to patient epidemiological data, and compared with data from previous years. METHODS: Agar dilution and minimum inhibitory concentration (MIC) gradient strip methodologies were used to determine the antimicrobial susceptibility (using EUCAST clinical breakpoints, where available) of 3239 N. gonorrhoeae isolates from 26 countries across the EU/EEA. Significance of differences compared with Euro-GASP results in previous years was analysed using Z-test and the Pearson's χ2 test was used to assess significance of odds ratios for associations between patient epidemiological data and antimicrobial resistance. RESULTS: European N. gonorrhoeae isolates collected between 2016 and 2019 displayed shifting MIC distributions for; ceftriaxone, with highly susceptible isolates increasing over time and occasional resistant isolates each year; cefixime, with highly-susceptible isolates becoming increasingly common; azithromycin, with a shift away from lower MICs towards higher MICs above the EUCAST epidemiological cut-off (ECOFF); and ciprofloxacin which is displaying a similar shift in MICs as observed for azithromycin. In 2019, two isolates displayed ceftriaxone resistance, but both isolates had MICs below the azithromycin ECOFF. Cefixime resistance (0.8%) was associated with patient sex, with resistance higher in females compared with male heterosexuals and men-who-have-sex-with-men (MSM). The number of countries reporting isolates with azithromycin MICs above the ECOFF increased from 76.9% (20/26) in 2016 to 92.3% (24/26) in 2019. Isolates with azithromycin MICs above the ECOFF (9.0%) were associated with pharyngeal infection sites. Following multivariable analysis, ciprofloxacin resistance remained associated with isolates from MSM and heterosexual males compared with females, the absence of a concurrent chlamydial infection, pharyngeal infection sites and patients ≥ 25 years of age. CONCLUSIONS: Resistance to ceftriaxone and cefixime remained uncommon in EU/EEA countries in 2019 with a significant decrease in cefixime resistance observed between 2016 and 2019. The significant increase in azithromycin "resistance" (azithromycin MICs above the ECOFF) threatens the effectiveness of the dual therapy (ceftriaxone + azithromycin), i.e., for ceftriaxone-resistant cases, currently recommended in many countries internationally and requires close monitoring.

Towards the development of a biobased economy in Europe and India.

India has emerged as a key player with a high potential to develop a biomass and biobased economy due to its large geographic size and the massive amounts of agricultural and non agricultural biomass produced. India has joined hands with Europe to synchronize its efforts to create and facilitate the development of a biobased economy in this country. This paper aims to examine common research and development actions between the European Union (EU) and India to facilitate the development of these biobased economies. As a base, a thorough study has been performed considering the biomass potential and current status of the bioeconomy in both the EU and India based on the distillation of a series of 80 potential recommendations. The recommendations were grouped into four major categories: (1) biomass production, (2) by-products/waste, (3) biorefineries and (4) policy, market, and value-added products. A questionnaire was designed and distributed to key stakeholders belonging to: academia, industry, and policymakers in both India and the EU. A total of 231 responses were received and analyzed, based on the key recommendations made for the essential research and development topics that are of prime importance to develop biobased economies in both the EU and India. The findings of this study suggest recognizing the value-added contributions made by biobased products such as: food, feed, valuable materials and chemicals in both regions. It is important to reduce the overall process costs and minimize the environmental impacts of such a biobased economy.

Ten years of external quality assessment (EQA) of Neisseria gonorrhoeae antimicrobial susceptibility testing in Europe elucidate high reliability of data.

BACKGROUND: Confidence in any diagnostic and antimicrobial susceptibility testing data is provided by appropriate and regular quality assurance (QA) procedures. In Europe, the European Gonococcal Antimicrobial Susceptibility Programme (Euro-GASP) has been monitoring the antimicrobial susceptibility in Neisseria gonorrhoeae since 2004. Euro-GASP includes an external quality assessment (EQA) scheme as an essential component for a quality-assured laboratory-based surveillance programme. Participation in the EQA scheme enables any problems with the performed antimicrobial susceptibility testing to be identified and addressed, feeds into the curricula of laboratory training organised by the Euro-GASP network, and assesses the capacity of individual laboratories to detect emerging new, rare and increasing antimicrobial resistance phenotypes. Participant performance in the Euro-GASP EQA scheme over a 10 year period (2007 to 2016, no EQA in 2013) was evaluated. METHODS: Antimicrobial susceptibility category and MIC results from the first 5 years (2007-2011) of the Euro-GASP EQA were compared with the latter 5 years (2012-2016). These time periods were selected to assess the impact of the 2012 European Union case definitions for the reporting of antimicrobial susceptibility. RESULTS: Antimicrobial susceptibility category agreement in each year was ≥91%. Discrepancies in susceptibility categories were generally because the MICs for EQA panel isolates were on or very close to the susceptibility or resistance breakpoints. A high proportion of isolates tested over the 10 years were within one (≥90%) or two (≥97%) MIC log2 dilutions of the modal MIC, respectively. The most common method used was Etest on GC agar base. There was a shift to using breakpoints published by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in the latter 5 years, however overall impact on the validity of results was limited, as the percentage categorical agreement and MIC concordance changed very little between the two five-year periods. CONCLUSIONS: The high level of comparability of results in this EQA scheme indicates that high quality data are produced by the Euro-GASP participants and gives confidence in susceptibility and resistance data generated by laboratories performing decentralised testing.

The European gonococcal antimicrobial surveillance programme (Euro-GASP) appropriately reflects the antimicrobial resistance situation for Neisseria gonorrhoeae in the European Union/European Economic Area.

BACKGROUND: European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) antimicrobial resistance (AMR) data are used to inform gonorrhoea treatment guidelines; therefore the data need to be robust and representative. We assessed the extent to which Euro-GASP reflects national measures of the AMR situation for Neisseria gonorrhoeae across the European Union/European Economic Area (EU/EEA). METHODS: We compared data from Euro-GASP with published national gonococcal AMR data from 15 countries for azithromycin, cefixime and ciprofloxacin for the period 2009 to 2013 and performed Poisson regression to identify differences (p < 0.05) between the proportions of resistant isolates. The 2014 Euro-GASP AMR data for each country (n = 19) were weighted to account for differences in the distribution of patient characteristics between Euro-GASP and EU/EEA epidemiological gonorrhoea surveillance data. Data were compared to determine whether estimates of resistance levels differed with regards to the 5% threshold used to assess the clinical utility of first-line gonorrhoea treatments. We assessed the quality of decentralised testing by comparing AMR data for isolates tested both centrally and in the participating laboratories, and by evaluating external quality assessment (EQA) performance. RESULTS: There was no significant difference for azithromycin, cefixime and ciprofloxacin resistance when Euro-GASP country data were compared with data from national reports. Weighting slightly altered the Euro-GASP AMR estimates (by between - 4.7 and 4.7% from the unweighted estimates). Weighting resulted in greater changes in estimates of resistance to azithromycin (from - 9.5 to 2.7%) and ciprofloxacin (from - 14.8 to 17.9%) in countries with low isolate numbers and low completeness of reporting (n = 3). Weighting caused AMR levels to fall below or above the 5% threshold for cefixime or azithromycin, respectively in only two countries. Susceptibility category data submitted from the decentralised Euro-GASP laboratories were concordant with the Euro-GASP data (> 90%). EQA performance was also good; < 5% of the minimum inhibitory concentration (MIC) results differed by > 4-fold from the modal MIC of the EQA isolate. CONCLUSIONS: The overall prevalence of AMR reported by Euro-GASP reflects closely the AMR situation for N. gonorrhoeae in the EU/EEA. Euro-GASP data can be used to provide robust AMR estimates to inform the European guideline for the management of gonorrhoea.

CRISPR-Cas9 and the Promise of a Better Future.

Due to its simplicity, low cost and accuracy, CRISPR-Cas9 has become a promising new technique in the field of gene editing. However, despite its virtues, it is not yet immune to scientific hazards and ethical legal concerns. These concerns have been used to justify opposition to genetic manipulation, and have led to some regulations to ban or impose a moratorium based on the precautionary principle. In Europe, regulation mostly comes from the European Union and the Council of Europe, both very cautious towards gene editing. In this article, two arguments on the future legal framework of CRISPR-Cas9 are made. The first is that continued research will contribute to more scientific accuracy; thus, the precautionary principle should promote regulated research to achieve this aim. The second is that most of the legal and ethical concerns surrounding CRISPR-Cas9 are based on unfounded prejudice emanating from a mystical understanding of the human genome.

Stably high azithromycin resistance and decreasing ceftriaxone susceptibility in Neisseria gonorrhoeae in 25 European countries, 2016.

BACKGROUND: The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) performs annual sentinel surveillance of Neisseria gonorrhoeae susceptibility to therapeutically relevant antimicrobials across the European Union/European Economic Area (EU/EEA). We present the Euro-GASP results from 2016 (25 countries), linked to patient epidemiological data, and compared with data from previous years. METHODS: Agar dilution and minimum inhibitory concentration (MIC) gradient strip methodologies were used to determine the antimicrobial susceptibility (using EUCAST breakpoints) of 2660 N. gonorrhoeae isolates from 25 countries across the EU/EEA. Significance of differences compared with Euro-GASP results in previous years was analysed using Z-tests. RESULTS: No isolates with resistance to ceftriaxone (MIC > 0.125 mg/L) were detected in 2016 (one in 2015). However, the proportion of isolates with decreased susceptibility to ceftriaxone (MICs from 0.03 mg/L to 0.125 mg/L) increased significantly (p = 0.01) from 2015 to 2016. There were 14 (0.5%) isolates with ceftriaxone MICs 0.125 mg/L (on the resistance breakpoint), of which one isolate was resistant to azithromycin and four showed intermediate susceptibility to azithromycin. Cefixime resistance was detected in 2.1% of isolates in 2016 compared with 1.7% in 2015 (p = 0.26) and azithromycin resistance in 7.5% in 2016 compared with 7.1% in 2015 (p = 0.74). Seven (0.3%) isolates from five countries displayed high-level azithromycin resistance (MIC≥256 mg/L) in 2016 compared with five (0.2%) isolates in 2015. Resistance rate to ciprofloxacin was 46.5% compared with 49.4% in 2015 (p = 0.06). No isolates were resistant to spectinomycin and the MICs of gentamicin remained stable compared with previous years. CONCLUSIONS: Overall AMR rates in gonococci in EU/EEA remained stable from 2015 to 2016. However, the ceftriaxone MIC distribution shifted away from the most susceptible (≤0.016 mg/L) and the proportion of isolates with decreased susceptibility to ceftriaxone increased significantly. This development is of concern as current European gonorrhoea management guideline recommends ceftriaxone 500 mg plus azithromycin 2 g as first-line therapy. With azithromycin resistance at 7.5%, the increasing ceftriaxone MICs might soon threaten the effectiveness of this therapeutic regimen and requires close monitoring.

European Union implementation of Article 5.3 of the Framework Convention on Tobacco Control.

BACKGROUND: Article 5.3 of the World Health Organization's Framework Convention on Tobacco Control (FCTC) requires Parties to the agreement to take proactive measures to protect health policy from the vested interests of the tobacco industry. Parties to the FCTC are required to submit periodic reports to the Convention Secretariat on the efforts undertaken to implement it. Previous analyses of national compliance with the FCTC suggest that Article 5.3 implementation is piecemeal and insufficient in many contexts, with governments relying on general transparency and other existing policies for the purpose of Article 5.3 implementation. No in-depth study of Article 5.3 compliance within the European Union (EU) - a signatory to the Convention - has been undertaken. This study seeks to assess the extent of Article 5.3 compliance in European Union institutions, through an analysis of the mechanisms in place in the European Commission and European Parliament. It analyses EU documents relevant to Article 5.3 compliance, as well as semi-structured interviews with policy actors in the EU institutions and the field of tobacco control. RESULTS: As with many national governments, Article 5.3 compliance within EU institutions is partial and incomplete. Much of the compliance activity cited in EU reports is derived from general codes of conduct for EU staff and the Juncker Commission's transparency agenda. Interview respondents reveal widespread lack of knowledge about the existence of the FCTC and Article 5.3 amongst key policy actors across the institutions. Within the Commission policies vary greatly between Directorates General, and issues surrounding the conceptualisation of the role of Members of the European Parliament affect implementation in that context. While there is growing awareness of the issue in both the Commission and the Parliament, in large part as a result of the experience of lobbying over the Tobacco Products Directive, there remains considerable resistance in both institutions to further substantive action to implement Article 5.3. CONCLUSIONS: We recommend that a binding and comprehensive policy and code of conduct, specifically designed for the implementation of Article 5.3 and based on the World Health Organization's guidelines, be created to cover the activities of all employees of all EU institutions. Crucially, such guidelines would need to deal explicitly with third parties acting for the tobacco industry.

Mapping the Teaching of Laboratory Animal Science and Medicine in the European Union and European Free Trade Area.

Developing a common market and allowing free movement of goods, services, and people is one of the main objectives of the European Union (EU) and the European Free Trade Area. In the field of scientific research, Directive 2010/63/EU on the protection of animals used for scientific purposes aims to improve the welfare of laboratory animals by following the principle of the 3Rs (replacement, reduction, and refinement). Each breeder, supplier, and user must appoint a designated veterinarian to advise on the well-being and treatment of the animals. In our report we investigate how the undergraduate veterinary curriculum prepares future veterinarians for the role of designated veterinarian, by analyzing data from 77 European veterinary education establishments. Over 80% of them provide training in laboratory animal science and medicine in their curriculum. All countries in the EU and the European Free Trade Area, having national veterinary schools, include such training in the curriculum of at least one of their establishments. Laboratory animal science and medicine courses can be obligatory or elective and are often part of more than one subject in the veterinary curricula. Post-graduate courses or programs are available at more than 50% of those veterinary schools. Most authorities in the European region consider graduate veterinarians ready to seek the role as designated veterinarian immediately after graduation.

Overall Low Extended-Spectrum Cephalosporin Resistance but high Azithromycin Resistance in Neisseria gonorrhoeae in 24 European Countries, 2015.

BACKGROUND: Surveillance of Neisseria gonorrhoeae antimicrobial susceptibility in Europe is performed through the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP), which additionally provides data to inform the European gonorrhoea treatment guideline; currently recommending ceftriaxone 500 mg plus azithromycin 2 g as first-line therapy. We present antimicrobial susceptibility data from 24 European countries in 2015, linked to epidemiological data of patients, and compare the results to Euro-GASP data from previous years. METHODS: Antimicrobial susceptibility testing by MIC gradient strips or agar dilution methodology was performed on 2134 N. gonorrhoeae isolates and interpreted using EUCAST breakpoints. Patient variables associated with resistance were established using logistic regression to estimate odds ratios (ORs). RESULTS: In 2015, 1.7% of isolates were cefixime resistant compared to 2.0% in 2014. Ceftriaxone resistance was detected in only one (0.05%) isolate in 2015, compared with five (0.2%) in 2014. Azithromycin resistance was detected in 7.1% of isolates in 2015 (7.9% in 2014), and five (0.2%) isolates displayed high-level azithromycin resistance (MIC ≥ 256 mg/L) compared with one (0.05%) in 2014. Ciprofloxacin resistance remained high (49.4%, vs. 50.7% in 2014). Cefixime resistance significantly increased among heterosexual males (4.1% vs. 1.7% in 2014), which was mainly attributable to data from two countries with high cefixime resistance (~11%), however rates among men-who-have-sex-with-men (MSM) and females continued to decline to 0.5% and 1%, respectively. Azithromycin resistance in MSM and heterosexual males was higher (both 8.1%) than in females (4.9% vs. 2.2% in 2014). The association between azithromycin resistance and previous gonorrhoea infection, observed in 2014, continued in 2015 (OR 2.1, CI 1.2-3.5, p < 0.01). CONCLUSIONS: The 2015 Euro-GASP sentinel system revealed high, but stable azithromycin resistance and low overall resistance to ceftriaxone and cefixime. The low cephalosporin resistance may be attributable to the effectiveness of the currently recommended first-line dual antimicrobial therapy; however the high azithromycin resistance threatens the effectiveness of this therapeutic regimen. Whether the global use of azithromycin in mono- or dual antimicrobial therapy of gonorrhoea is contributing to the global increases in azithromycin resistance remains to be elucidated. The increasing cefixime resistance in heterosexual males also needs close monitoring.

Genome-Editing Products Line up for the Market: Will Europe Harvest the Benefits from Science and Innovation?

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technologies have revolutionized genome editing, significantly advancing the improvement of cultivated crop species. This review provides an overview of genome-edited crops that have either reached the market or received the necessary approvals but are not yet available to consumers. We analyze various genome-editing studies to understand the distribution of different genome-editing systems, the types of site-directed nucleases employed, and the geographical spread of these studies, with a specific focus on global and European contexts. Additionally, we examine the target crops involved. The review also outlines the multiple steps required for the legal acceptance of genome-edited crops within European jurisdictions. We conclude with suggestions for the future prospects of genome-editing research in Europe, aiming to streamline the approval process and enhance the development and adoption of genome-edited crops.

The Role of Promoting Agricultural and Food Products Certified with European Union Quality Schemes.

This study delves into the effectiveness of digital marketing strategies in promoting local agricultural and food products in Romania, certified with European Union quality schemes. By examining consumer profiles, preferences, and their awareness of EU quality labels, the research uncovers the motivations driving purchasing decisions and the influence of digital marketing on these choices. Utilizing quantitative methods, including a comprehensive survey across 903 respondents, the study identifies four distinct consumer segments: Eco-Advocates, Les Connaisseurs, Price-Sensitives, and Traditionalists. These segments exhibit unique behaviors and attitudes toward certified products. The research highlights the potential of digital marketing to significantly alter consumer behavior toward EU-certified products, underscoring the importance of tailored communication strategies. It contributes to the understanding of consumer segmentation in the context of European Union quality schemes, providing valuable insights for policymakers, marketers, and producers. The findings advocate for enhanced digital marketing efforts to increase awareness and appreciation of these certified products, thereby supporting the broader objectives of quality and certification in the European agricultural and food product sector.

Strategies for Traceability to Prevent Unauthorised GMOs (Including NGTs) in the EU: State of the Art and Possible Alternative Approaches.

The EU's regulatory framework for genetically modified organisms (GMOs) was developed for "classical" transgenic GMOs, yet advancements in so-called "new genomic techniques (NGTs)" have led to implementation challenges regarding detection and identification. As traceability can complement detection and identification strategies, improvements to the existing traceability strategy for GMOs are investigated in this study. Our results are based on a comprehensive analysis of existing traceability systems for globally traded agricultural products, with a focus on soy. Alternative traceability strategies in other sectors were also analysed. One focus was on traceability strategies for products with characteristics for which there are no analytical verification methods. Examples include imports of "conflict minerals" into the EU. The so-called EU Conflict Minerals Regulation requires importers of certain raw materials to carry out due diligence in the supply chain. Due diligence regulations, such as the EU's Conflict Minerals Regulation, can legally oblige companies to take responsibility for certain risks in their supply chains. They can also require the importer to prove the regional origin of imported goods. The insights from those alternative traceability systems are transferred to products that might contain GMOs. When applied to the issue of GMOs, we propose reversing the burden of proof: All companies importing agricultural commodities must endeavour to identify risks of unauthorised GMOs (including NGTs) in their supply chain and, where appropriate, take measures to minimise the risk to raw material imports. The publication concludes that traceability is a means to an end and serves as a prerequisite for due diligence in order to minimise the risk of GMO contamination in supply chains. The exemplary transfer of due diligence to a company in the food industry illustrates the potential benefits of mandatory due diligence, particularly for stakeholders actively managing non-GMO supply chains.

Comparative analysis of GMO regulatory requirements for AAV vectors in the EU and Japan focusing on the shedding data and containment measures.

INTRODUCTION: Recombinant viral-based gene therapy products, such as those incorporating adeno-associated viruses (AAVs), fall under the category of genetically modified organisms (GMOs). The European Union (EU) countries and Japan must obtain environmental risk assessment (ERA) approval for the use of GMOs before starting any clinical trials. It has been reported that the development of GMO-containing products in these two regions encounters several regulatory obstacles due to the longer regulatory procedures and document preparation for ERA. AREAS COVERED: In this article, we comparatively analyzed the ERA document requirements in the EU and Japan for AAV-based recombinant medicinal products to highlight the differences in the context of potential future attempts of convergence. Additionally, we analyzed non-clinical and clinical shedding data requirements, which are key components of ERA reviews in the EU and Japan. Lastly, we compared the containment measures to minimize the spread of GMOs in the environment in the EU and Japan. EXPERT OPINION: Based on our comparative analysis, we present several policy recommendations of standardizing and simplifying the application materials and procedures for the ERA regulations on GMOs in the EU and Japan in the mid-, and long-term timeframe to achieve global regulatory convergence.

The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP)--a sentinel approach in the European Union (EU)/European Economic Area (EEA).

Antimicrobial resistance in Neisseria gonorrhoeae is monitored in the European Union/European Economic Area through the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) coordinated by the European Centre for Disease Prevention and Control. Euro-GASP includes a sentinel surveillance programme which aims to detect in a timely manner changes in resistance patterns and inform treatment guidelines. The programme aims to test a representative number of isolates from each European Union/European Economic Area member state per year for a range of therapeutically relevant antimicrobials through a biannual hybrid centralised/decentralised system. Testing is supported by an External Quality Assurance programme and a laboratory training programme. Participation in the programme has increased to 21 countries in 2012. Euro-GASP has been able to detect the rapid spread of isolates with decreased susceptibility to cefixime across Europe in 2010 and 2011. Results from the programme have informed changes in European treatment guidelines for gonorrhoea and led to the development of the 'Response plan to control and manage the threat of multidrug resistant gonorrhoea in Europe'. Future challenges for Euro-GASP include supporting countries to participate in Euro-GASP through decentralised testing, improving timeliness and epidemiological data quality, and increasing participation from Eastern Europe.

Analysis of the renewed European Medical Device Regulations in the frame of the non - EU regulatory landscape during the COVID facilitated change.

The term "Medical devices" includes technology-based devices or articles, both basic and complex. Due to these types of variations, a strict, robust, transparent, and sustainable regulatory framework is required. In recent clinical practice, incidents including the breast implant and the hip replacement crisis have made it necessary to improve the regulatory and compliance approaches for the industry to ensure the manufacturing and distribution of safe and innovative MDs within the EU. In response to this, the EU revised the laws governing medical devices and in vitro diagnostics to align with the developments of the sector, address critical safety issues and support innovation. The new regulation (EU) 2017/745 on Medical Devices (MDR) is now applicable from May 26 2021 and the In Vitro Diagnostic Medical Devices Regulation (EU) 2017/746 will take effect from May 2022.In this review, we aim to provide an update on the new Medical Device Regulations in the context of the current medical needs of the world, and also to give a glimpse at the non-EU regulatory landscape. Finally, we take a look at the closed-system transfer devices (CSTD) and COVID facilitated changes promoting demand for continuous improvement and trends in the pharmaceutical and medical industry related areas.

The 3Rs in animal welfare bodies at Swedish universities - knowledge, attitudes, implementation.

The implementation of the 3Rs (replacement, reduction and refinement) is emphasized in EU Directive 2010/63. The task of the animal welfare bodies (AWB) is to strengthen animal welfare and develop the 3Rs at research animal facilities. In 2016, we surveyed the knowledge on, attitudes towards and implementation of the 3Rs within AWBs at eight major Swedish universities. Based on responses of 34 closed-ended questions from 44 of 90 AWB members, the overall attitude towards the 3Rs was positive. AWB members did not believe that the 3Rs slow down innovation or result in increased costs, and refinement was considered beneficial for research quality. AWB members were particularly positive towards refinement questions in the survey. A majority of the AWB members predicted that alternative methods will never replace animal use. Researchers as a group represented in the AWBs were significantly less positive towards the 3Rs compared to the group of veterinarians. The tasks of the AWBs, e.g., giving advice on the 3Rs and following up on animal use in projects, were often not carried out in the AWB or not known by the respondents. Our results indicate a need for more practical and regulatory guidance and support to the AWBs. To reach the goal of the EU Directive to phase out animal use in research and education, we suggest that technical expertise in replacement techniques is included in the AWBs. We emphasize the need to strengthen the awareness of the 3Rs among researchers at Swedish universities.

Relations between the EU, Turkey, and Japan: dissonances in the strategic triangle.

This paper considers how the three sets of bilateral relations, between the European Union (EU) and Japan, the EU and Turkey, and Turkey and Japan, have developed (or been underdeveloped) and how the three have failed to form a strategic triangle that could potentially be beneficial for dealing with regional and international problems more efficiently. One of the main arguments is that, although all three sides of this triangle have developed significant economic relationships, their political relationships are less consolidated. Such a phenomenon is largely illustrated by the following three elements of this triangle: a deteriorated relationship between the EU and Turkey, an underutilised relationship between Japan and the EU, and an extant relationship between Japan and Turkey. This paper analyses the elements that have impeded or continue to hinder constructive political dialogue. It concludes that the potential for improvement in the three sets of bilateral relations is slight, in the short term, with Japan, in particular, finding it increasingly difficult to strike a good balance between developing the relationship with the EU while maintaining historical ties with Turkey.

Potentially inappropriate medications involved in drug-drug interactions at hospital discharge in Croatia.

Background The potentially inappropriate medications (PIMs) and drug-drug interactions (DDIs) can significantly affect patient safety in the elderly, especially at transition of health care. Objective The aim of this study is to evaluate PIMs involved in potentially clinically significant DDIs in prescribed pharmacotherapy of elderly patients at hospital discharge. Setting Internal Medicine Clinic of University Hospital Dubrava, Zagreb, Croatia. Method During a 16-month period, the pharmacotherapy data were assessed using Lexicomp Online screening software to identify category C (monitor drug therapy), D (consider therapy modification) and X (avoid combination) DDIs. The European Union (EU)(7)-PIM criteria were applied to detect inappropriately prescribed medications involved in DDIs. Clinical pharmacists obtained data from patients' medical records and patient/caregiver interviews. Main outcome measure The incidence of PIMs involved in potentially clinically significant DDIs. Results A total of 364 consecutive elderly patients were enrolled in the study. The mean number of prescription medications at discharge was 9.3. Overall, 2833 potentially clinically significant DDIs were identified: 2445 (86.3%) of them were category C, 347 (12.3%) category D and 41 (1.4%) were category X interactions. A total of 1164 PIMs were involved in 31.2% of category C interactions, 60.2% of category D interactions and 43.9% of category X interactions. The most frequent PIMs involved in potentially clinically significant DDIs were tramadol, benzodiazepines, moxonidine, vildagliptin and metoclopramide. Conclusion A very high incidence of DDIs in elderly patients and a high incidence of PIMs involved in DDIs was determined at hospital discharge.

Analysis of the New Kuznets Relationship: Considering Emissions of Carbon, Methanol, and Nitrous Oxide Greenhouse Gases-Evidence from EU Countries.

Decreased greenhouse gas emissions (GHG) are urgently needed in view of global health threat represented by climate change. The goal of this paper is to test the validity of the Environmental Kuznets Curve (EKC) hypothesis, considering less common measures of environmental burden. For that, four different estimations are done, one considering total GHG emissions, and three more taking into account, individually, the three main GHG gases-carbon dioxide (CO2), nitrous oxide (N2O), and methane gas (CH4)-considering the oldest and most recent economies adhering to the EU27 (the EU 15 (Old Europe) and the EU 12 (New Europe)) separately. Using panel dynamic fixed effects (DFE), dynamic ordinary least squares (DOLS), and fully modified ordinary least squares (FMOLS) techniques, we validate the existence of a U-shaped relationship for all emission proxies considered, and groups of countries in the short-run. Some evidence of this effect also exists in the long-run. However, we were only able to validate the EKC hypothesis for the short-run in EU 12 under DOLS and the short and long-run using FMOLS. Confirmed is the fact that results are sensitive to models and measures adopted. Externalization of problems globally takes a longer period for national policies to correct, turning global measures harder and local environmental proxies more suitable to deeply explore the EKC hypothesis.

Pharmaceutical Manufacturing in the EU and the EU-US Mutual Recognition Agreement.

The pharmaceutical industry is one of the most competitive sectors in Europe and has a strong presence in many European Union (EU) countries. The mutual recognition agreement (MRA) for inspections of medicines manufacturers between the United States (US) Food and Drug Administration (FDA) and the EU started by the end of 2017 and gradually extended to all EU member states (MSs) in July 2019. We quantified the number of FDA and EU good manufacturing practice (GMP) inspections carried out in each other's territory between 2009 and 2018. The five EU MSs with the largest number of FDA inspections were Germany, followed by Italy, France, the United Kingdom (UK), and Spain. All of them, with the exception of Germany, were included in the group of the first eight EU MSs recognized by the FDA in the context of the MRA. In 2018, these five EU MSs were within the top 10 EU exporters of pharmaceutical products to the US. Four of these five EU MSs (Italy, Germany, France, and the UK) accounted for 53.4% of the total pharmaceutical production in the EU in 2018. We also studied the type of manufacturing operations covered by the manufacturer's authorizations issued by each EU MS for the manufacturers within its territory. We verified a high prevalence of conventional technology versus complex technology manufacturing for many EU countries. Going forward, this unbalance should be addressed at a national and EU level. Supporting for instance (bio)pharmaceutical manufacturing through pharma policy initiatives, especially for EU countries with a lower level of innovation and technological development, would promote the pharmaceutical manufacturing sustainability and competitiveness of these countries. The full implementation of the MRA between the US FDA and the EU can make it faster and less costly for both sides to bring medicines to the market, improving future competitiveness of the EU and the US pharmaceutical industry.