Directorate-General for Health and Food Safety

Many countries are seeking to improve health care delivery by reviewing the roles of health professionals, including nurses. Developing new and more advanced roles for nurses could improve access to care in the face of a limited or diminishing supply of doctors. It might also contain costs by delegating tasks away from more expensive doctors. This paper reviews the development of advanced practice nurses in 12 countries (Australia, Belgium, Canada, Cyprus, Czech Republic, Finland, France, Ireland, Japan, Poland, United Kingdom and United States), with a particular focus on their roles in primary care. It also reviews the evaluations of impacts on patient care and cost.

Multimorbidity, which is defined as the co-occurrence of two or more chronic conditions, has moved onto the priority agenda for many health policymakers and healthcare providers. Patients with multimorbidity are high utilizers of healthcare resources and are some of the most costly and difficult-to-treat patients in Europe. Preventing and improving the way multimorbidity is managed is now a key priority for many countries, and work is at last underway to develop more sustainable models of care. Unfortunately, this effort is being hampered by a lack of basic knowledge about the aetiology, epidemiology, and risk factors for multimorbidity, and the efficacy and cost-effectiveness of different interventions. The European Commission recognizes the need for reform in this area and has committed to raising awareness of multimorbidity, encouraging innovation, optimizing the use of existing resources, and coordinating the efforts of different stakeholders across the European Union. Many countries have now incorporated multimorbidity into their own healthcare strategies and are working to strengthen their prevention efforts and develop more integrated models of care. Although there is some evidence that integrated care for people with multimorbidity can create efficiency gains and improve health outcomes, the evidence is limited, and may only be applicable to high-income countries with relatively strong and well-resourced health systems. In low- to middle-income countries, which are facing the double burden of infectious and chronic diseases, integration of care will require capacity building, better quality services, and a stronger evidence base.

Donation after circulatory death (DCD) has become an accepted practice in many countries and remains a focus of intense interest in the transplant community. The present study is aimed at providing a description of the current situation of DCD in European countries. Specific questionnaires were developed to compile information on DCD practices, activities and post-transplant outcomes. Thirty-five countries completed the survey. DCD is practiced in 18 countries: eight have both controlled DCD (cDCD) and uncontrolled DCD (uDCD) programs, 4 only cDCD and 6 only uDCD. All these countries have legally binding and/or nonbinding texts to regulate the practice of DCD. The no-touch period ranges from 5 to 30 min. There are variations in ante and post mortem interventions used for the practice of cDCD. During 2008-2016, the highest DCD activity was described in the United Kingdom, Spain, Russia, the Netherlands, Belgium and France. Data on post-transplant outcomes of patients who receive DCD donor kidneys show better results with grafts obtained from cDCD versus uDCD donors. In conclusion, DCD is becoming increasingly accepted and performed in Europe, importantly contributing to the number of organs available and providing acceptable post-transplantation outcomes.

Data were collected on the prevalence of salmonella at different stages during the life cycle of 18 broiler flocks on different farms as well as during slaughter in different poultry slaughterhouses. For the isolation of salmonella, the highest sensitivity (93.9%) was obtained by enrichment in the semi-solid agar Diasalm. The 'overshoe method' utilizing several pairs of overshoes provided the highest sensitivity for determining the salmonella status of the broilers during rearing. A clear decrease of the relative importance of the first production stages was demonstrated for the salmonella contamination of the end product, whereas horizontal transmission of salmonella to broilers during rearing and to broiler carcasses in the slaughterhouse was shown to be the main determinative factor. Ten of the 18 flocks received a salmonella positive status with the highest shedding occurring during the first 2 weeks of rearing. The shedding of the animals was significantly negatively influenced by the use of subtherapeutic or therapeutic doses of antibiotics. The intake of portable material in the broiler house was identified as the most important risk factor for horizontal transmission. Significant associations were found between the contamination level of a flock and hygiene of the broiler house, feed and water in the broiler house and both animal and non-animal material sampled in the environment. No correlation was found between contamination during the rearing period and contamination found after slaughtering. The presence of faecal material in the transport crates and predominantly the identity of the slaughterhouse seemed to be the determining factors for carcass quality. Improved hygiene management during transport of broilers and in some slaughterhouses could significantly reduce the risk of salmonella contamination of poultry meat.

A lethal intoxication case, which occurred in Brussels, Belgium, is described. A 20-year-old man died following the ingestion of pasta contaminated with Bacillus cereus. Emetic strains of B. cereus were isolated, and high levels of cereulide (14.8 μg/g) were found in the spaghetti meal.

BACKGROUND: Due to global mercury pollution and the adverse health effects of prenatal exposure to methylmercury (MeHg), an assessment of the economic benefits of prevented developmental neurotoxicity is necessary for any cost-benefit analysis. METHODS: Distributions of hair-Hg concentrations among women of reproductive age were obtained from the DEMOCOPHES project (1,875 subjects in 17 countries) and literature data (6,820 subjects from 8 countries). The exposures were assumed to comply with log-normal distributions. Neurotoxicity effects were estimated from a linear dose-response function with a slope of 0.465 Intelligence Quotient (IQ) point reduction per μg/g increase in the maternal hair-Hg concentration during pregnancy, assuming no deficits below a hair-Hg limit of 0.58 μg/g thought to be safe. A logarithmic IQ response was used in sensitivity analyses. The estimated IQ benefit cost was based on lifetime income, adjusted for purchasing power parity. RESULTS: The hair-mercury concentrations were the highest in Southern Europe and lowest in Eastern Europe. The results suggest that, within the EU, more than 1.8 million children are born every year with MeHg exposures above the limit of 0.58 μg/g, and about 200,000 births exceed a higher limit of 2.5 μg/g proposed by the World Health Organization (WHO). The total annual benefits of exposure prevention within the EU were estimated at more than 600,000 IQ points per year, corresponding to a total economic benefit between €8,000 million and €9,000 million per year. About four-fold higher values were obtained when using the logarithmic response function, while adjustment for productivity resulted in slightly lower total benefits. These calculations do not include the less tangible advantages of protecting brain development against neurotoxicity or any other adverse effects. CONCLUSIONS: These estimates document that efforts to combat mercury pollution and to reduce MeHg exposures will have very substantial economic benefits in Europe, mainly in southern countries. Some data may not be entirely representative, some countries were not covered, and anticipated changes in mercury pollution all suggest a need for extended biomonitoring of human MeHg exposure.

Hyperuricemia (HU) and tumour lysis syndrome (TLS) are complications of acute leukaemia and non-Hodgkin lymphoma (NHL) leading to increased morbidity and mortality. The objective of this study was to define incidence and calculate health care cost associated with HU and TLS. 788 acute leukaemia and NHL patients from Belgium, The Netherlands, Spain and UK were screened retrospectively for HU and TLS. Resource use related to HU and TLS was recorded and costs were calculated applying local unit costs. Results showed that HU occurred in 18.9% of patients, and 27.8% of them fulfilled TLS criteria. The cost of HU without TLS was 672 euros (SE 181), the cost of TLS 7,342 euros (SE 1,412). TLS requiring dialysis incurred an average cost of 17,706 euros. In conclusion, it is noted that the observed incidence rates were lower than earlier reports. In addition, some risk factors for HU and TLS (e.g. paediatric patients versus adults) were not associated with increased rates of HU or TLS as a consequence of higher rates of prevention. TLS cases incurred 11 times higher costs than HU cases in which TLS was absent. The main cost drivers in TLS are interventions requiring intensive care.

We studied zoonotic transmission of Chlamydophila psittaci in 39 breeding facilities for Psittaciformes (cockatoos, parrots, parakeets, lories) that frequently used antimicrobial drugs. Genotypes A or E/B were detected in 14.9% of humans at these facilities. Information on antimicrobial drug use in Psittaciformes and a C. psittaci vaccine are urgently required.

From April 1998 to March 2000, 18 broiler flocks were followed from the hatchery to the slaughterhouse. Campylobacter was not found in the hatchery, 1-day-old chicks or in the rearing house before the arrival of the chicks. The infection of broiler flocks increased continuously during the rearing time, with a total of seven positive flocks at the end of rearing. Farms with Campylobacter-positive broilers were characterized by the circulation of Campylobacter in the environment (puddles, dung hill) and on the footwear of the farmer. The administration of antibiotics did not significantly reduce Campylobacter shedding. With the exception of one flock during rearing and a few flocks in the slaughterhouse with a mixed Campylobacter coli-Campylobacter jejuni infection, C. jejuni exclusively was found both during rearing and on the carcasses. A significant correlation exits between the contamination of the broilers during rearing and the carcasses after processing. No slaughterhouse was able to avoid contamination of carcasses when status-positive animals were delivered. Moreover, six negatively delivered flocks yielded positive carcasses, the result of a supplementary contamination, which occurred during transport and slaughtering.

The toxicity of methylmercury (MeHg) in humans is well established and the main source of exposure is via the consumption of large marine fish and mammals. Of particular concern are the potential neurodevelopmental effects of early life exposure to low-levels of MeHg. Therefore, it is important that pregnant women, children and women of childbearing age are, as far as possible, protected from MeHg exposure. Within the European project DEMOCOPHES, we have analyzed mercury (Hg) in hair in 1799 mother-child pairs from 17 European countries using a strictly harmonized protocol for mercury analysis. Parallel, harmonized questionnaires on dietary habits provided information on consumption patterns of fish and marine products. After hierarchical cluster analysis of consumption habits of the mother-child pairs, the DEMOCOPHES cohort can be classified into two branches of approximately similar size: one with high fish consumption (H) and another with low consumption (L). All countries have representatives in both branches, but Belgium, Denmark, Spain, Portugal and Sweden have twice as many or more mother-child pairs in H than in L. For Switzerland, Czech Republic, Hungary, Poland, Romania, Slovenia and Slovakia the situation is the opposite, with more representatives in L than H. There is a strong correlation (r=0.72) in hair mercury concentration between the mother and child in the same family, which indicates that they have a similar exposure situation. The clustering of mother-child pairs on basis of their fish consumption revealed some interesting patterns. One is that for the same sea fish consumption, other food items of marine origin, like seafood products or shellfish, contribute significantly to the mercury levels in hair. We conclude that additional studies are needed to assess and quantify exposure to mercury from seafood products, in particular. The cluster analysis also showed that 95% of mothers who consume once per week fish only, and no other marine products, have mercury levels 0.55 μg/g. Thus, the 95th percentile of the distribution in this group is only around half the US-EPA recommended threshold of 1 μg/g mercury in hair. Consumption of freshwater fish played a minor role in contributing to mercury exposure in the studied cohort. The DEMOCOPHES data shows that there are significant differences in MeHg exposure across the EU and that exposure is highly correlated with consumption of fish and marine products. Fish and marine products are key components of a healthy human diet and are important both traditionally and culturally in many parts of Europe. Therefore, the communication of the potential risks of mercury exposure needs to be carefully balanced to take into account traditional and cultural values as well as the potential health benefits from fish consumption. European harmonized human biomonitoring programs provide an additional dimension to national HMB programs and can assist national authorities to tailor mitigation and adaptation strategies (dietary advice, risk communication, etc.) to their country's specific requirements.

The analysis of safety data from spontaneous reporting systems has a proven value for the detection and analysis of the risks of medicines following their placement on the market and use in medical practice. EudraVigilance is the pharmacovigilance database to manage the collection and analysis of suspected adverse reactions to medicines authorised in the European Economic Area. EudraVigilance first operated in December 2001, with access to the database being governed by the EudraVigilance access policy. We performed a literature search including data up to December 2016 to demonstrate how the data from EudraVigilance has been used in scientific publications. We describe the results, including by type of publication, research topics and drugs involved. In 50% of the publications, the data are used to describe safety issues, in 44% to analyse methodologies used in pharmacovigilance activities and in 6% to support clinical perspectives. We also outline a description of the use of the database by the European Union regulatory network. Driven by the full implementation of the 2010 pharmacovigilance legislation, EudraVigilance has undergone further enhancements together with a major revision of its access policy, taking into account the use of the new individual case safety report standard developed by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use and the International Organization for Standardization. The aim of the broadened access is to facilitate more effective safety monitoring of authorised medicines, to make more data available for research and to provide better access to information on suspected adverse reactions for healthcare professionals and patients. In November 2017, the new full functionalities of EudraVigilance were launched, including the extensive web access to data on suspected adverse drug reactions and the possibilities for academic research institutions to request a more extensive dataset for the purposes of health research. The main objective of this article is to describe the new access to the database together with the opportunities that this new access can bring for research. It is intended to promote an appropriate use of the data to support the safe and effective use of medicines.

When ingested in sufficient numbers, probiotics are expected to confer one or more proven health benefits on the consumer. Theoretically, the effectiveness of a probiotic food product is the sum of its microbial quality and its functional potential. Whereas the latter may vary much with the body (target) site, delivery mode, human target population, and health benefit envisaged microbial assessment of the probiotic product quality is more straightforward. The range of stakeholders that need to be informed on probiotic quality assessments is extremely broad, including academics, food and biotherapeutic industries, healthcare professionals, competent authorities, consumers, and professional press. In view of the rapidly expanding knowledge on this subject, the Belgian Superior Health Council installed Working Group "8651 Probiotics" to review the state of knowledge regarding the methodologies that make it possible to characterize strains and products with purported probiotic activity. This advisory report covers three main steps in the microbial quality assessment process, i.e. (i) correct species identification and strain-specific typing of bacterial and yeast strains used in probiotic applications, (ii) safety assessment of probiotic strains used for human consumption, and (iii) quality of the final probiotic product in terms of its microbial composition, concentration, stability, authenticity, and labeling.

Bacterial toxins are food safety hazards causing about 10% of all reported foodborne outbreaks in Europe. Pertinent to Gram-positive pathogens, the most relevant toxins are emetic toxin and diarrheal enterotoxins of Bacillus cereus, neurotoxins of Clostridium botulinum, enterotoxin of Clostridium perfringens, and a family of enterotoxins produced by Staphylococcus aureus and some other staphylococci. These toxins are the most important virulence factors of respective foodborne pathogens and a primary cause of the related foodborne diseases. They are proteins or peptides that differ from each other in their size, structure, toxicity, toxicological end points, solubility, and stability, types of food matrix to which they are mostly related to. These differences influence the characteristics of required detection methods. Therefore, detection of these toxins in food samples, or detection of toxin production capacity in the bacterial isolate, remains one of the cornerstones of microbial food analysis and an essential tool in understanding the relevant properties of these toxins. Advanced research has led into new insights of the incidence of toxins, mechanisms of their production, their physicochemical properties, and their toxicological mode of action and dose-response profile. This review focuses on biological, immunological, mass spectrometry, and molecular assays as the most commonly used detection and quantification methods for toxins of B. cereus, C. botulinum, C. perfringens, and S. aureus. Gathered and analyzed information provides a comprehensive blueprint of the existing knowledge on the principles of these assays, their application in food safety, limits of detection and quantification, matrices in which they are applicable, and type of information they provide to the user.

Abstract This paper reports on the identification and full chemical characterization of isotonitazene ( N , N ‐diethyl‐2‐[5‐nitro‐2‐({4‐[(propan‐2‐yl)oxy]phenyl}methyl)‐1H‐benzimidazol‐1‐yl]ethan‐1‐amine), a potent NPS opioid and the first member of the benzimidazole class of compounds to be available on online markets. Interestingly, this compound was sold under the name etonitazene, a structural analog. Identification of isotonitazene was performed by gas chromatography mass spectrometry (GC–MS) and liquid chromatography time‐of‐flight mass spectrometry (LC‐QTOF‐MS), the latter identifying an exact‐mass m/z value of 411.2398. All chromatographic data indicated the presence of a single, highly pure compound. Confirmation of the specific benzimidazole regio‐isomer was performed using 1 H and 13 C NMR spectroscopy, after which the chemical characterization was finalized by recording Fourier‐transform (FT‐IR) spectra. A live cell‐based reporter assay to assess the in vitro biological activity at the μ‐opioid receptor (MOR) revealed that isotonitazene has a high potency (EC 50 of 11.1 nM) and efficacy (E max 180% of that of hydromorphone), thus confirming that this substance is a strong opioid. Isotonitazene has not been previously detected, either in powder form, or in biological fluids. The high potency and efficacy of isotonitazene, combined with the fact that this compound was being sold undiluted, represents an imminent danger to anyone aiming to use this powder.

Over the last two decades, important contributions were made at national, European and international levels to foster collaboration into rare diseases research. The European Union (EU) has put much effort into funding rare diseases research, encouraging national funding organizations to collaborate together in the E-Rare program, setting up European Reference Networks for rare diseases and complex conditions, and initiating the International Rare Diseases Research Consortium (IRDiRC) together with the National Institutes of Health in the USA. Co-ordination of the activities of funding agencies, academic researchers, companies, regulatory bodies, and patient advocacy organizations and partnerships with, for example, the European Research Infrastructures maximizes the collective impact of global investments in rare diseases research. This contributes to accelerating progress, for example, in faster diagnosis through enhanced discovery of causative genes, better understanding of natural history of rare diseases through creation of common registries and databases and boosting of innovative therapeutic approaches. Several examples of funded pre-clinical and clinical gene therapy projects show that integration of multinational and multidisciplinary expertize generates new knowledge and can result in multicentre gene therapy trials. International collaboration in rare diseases research is key to improve the life of people living with a rare disease.

AIMS: To determine the biodiversity of enterococci from slightly fermented sausages (chorizo and fuet) at species and strain level by molecular typing, while considering their safety aspects. METHODS AND RESULTS: Species-specific PCR and partial sequencing of 16S rRNA and sodA genes were used to identify enterococcal population. Enterococcus faecium was the most frequently isolated species followed by E. faecalis, E. hirae and E. durans. Randomly amplified polymorphic DNA (RAPD)-PCR revealed species-specific clusters and allowed strain typing. Sixty strains of 106 isolates exhibited different RAPD profiles indicating a high genetic variability. All the E. faecalis strains carried virulence genes (efaAfs, esp, agg and gelE) and all E. faecium isolates carried efaAfm gene. Enterococcus faecalis showed higher antibiotic resistance than the other species. Only one E. faecium strain showed vanA genotype (high-level resistance to glycopeptides) and E. gallinarum and E. casseliflavus/flavescens isolates showed vanC1 and vanC2/C3 genotypes (low-level resistance only to vancomycin) respectively. CONCLUSIONS: E. faecalis has been mainly associated with virulence factors and antimicrobial multi-resistance and, although potential risk for human health is low, the presence of this species in slightly fermented sausages should be avoided to obtain high quality products. SIGNIFICANCE AND IMPACT OF THE STUDY: The enterococcal population of slightly fermented sausages has been thoroughly characterized. Several relevant safety aspects have been revealed.

In January 2015, the Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) published its final opinion on "Potential health effects of exposure to electromagnetic fields." The purpose of this document was to update previous SCENIHR opinions in the light of recently available information since then, and to give special consideration to areas that had not been dealt with in the previous opinions or in which important knowledge gaps had been identified.

This study was carried out to assess the shelf life and microbiological safety of wheat bread during storage in a packaging system made of Ag/TiO 2 nanocomposite (Ag/TiO 2 ‐P) in comparison with bread packed in high density polyethylene (HDP‐P) and bread not subject to packaging (CS). The Ag/TiO 2 nanocomposite was prepared by sol–gel procedure, and its morphostructural characterization was performed by X‐ray diffraction, Fourier transform infrared spectroscopy and transmission electron microscopy. The Ag/TiO 2 ‐P was prepared via inclusion of nanocomposite between the polyethylene layers to avoid bread–nanocomposite contact. Chemical and microbial stability of bread expressed in terms of total fat, protein, sugar, lipid hydroperoxides and yeasts, moulds, and Bacillus subtilis and Bacillus cereus counts, respectively, was monitored for 6 days. Experimental data indicate that Ag/TiO 2 ‐P considerably extends the shelf life and microbiological safety of bread in comparison with HDP‐P and CS. A possible mechanism involved in the preservation of the bread is hypothesized. Copyright © 2014 John Wiley & Sons, Ltd.

The problem of modeling expert knowledge about numerical parameters in the field of reliability is reconsidered in the framework of possibility theory. Usually expert opinions about quantities such as failure rates are modeled, assessed, and pooled in the setting of probability theory. This approach does not seem to always be natural since probabilistic information looks too rich to be currently supplied by individuals. Indeed, information supplied by individuals is often incomplete, imprecise rather than tainted with randomness. Moreover, the probabilistic framework looks somewhat restrictive to express the variety of possible pooling modes. In this paper, the authors formulate a model of expert opinion by means of possibility distributions that are thought to better reflect the imprecision pervading expert judgments. They are weak substitutes to unreachable subjective probabilities. Assessment evaluation is carried out in terms of calibration and level of precision, respectively, measured by membership grades and fuzzy cardinality indexes. Finally, drawing from previous works on data fusion using possibility theory, the authors present various pooling modes with their formal model under various assumptions concerning the experts. A comparative experiment between two computerized systems for expert opinion analysis has been carried out, and its results are presented in this paper.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

The efficacy of a rapid test for detecting PrP(Sc) in central nervous system tissue was evaluated for the postmortem diagnosis of BSE at different times during the course of the disease. One hundred and six samples of brain, at the level of the medulla oblongata, and spinal cord, derived from the experimental study of the pathogenesis of BSE carried out in Great Britain between 1991 and 1995, were examined. PrP(Sc) was detected in the samples from most of the exposed animals killed 32 months or more after they had been exposed to the agent, and before the onset of clinical signs which were first recorded at 35 months. Comparisons with the results of histology, fibril detection, PrP immunohistochemistry and mouse bioassay indicated that the rapid test is at least as sensitive as these conventional confirmatory diagnostic methods and its result can be obtained more quickly.