Increased Levels of Multiresistant Bacteria and Resistance Genes after Wastewater Treatment and Their Dissemination into Lake Geneva, Switzerland

At present, very little is known about the fate and persistence of multiresistant bacteria (MRB) and their resistance genes in natural aquatic environments. Treated, but partly also untreated sewage of the city of Lausanne, Switzerland is discharged into Vidy Bay (Lake Geneva) resulting in high levels of contamination in this part of the lake. In the present work we have studied the prevalence of MRB and resistance genes in the wastewater stream of Lausanne. Samples from hospital and municipal raw sewage, treated effluent from Lausanne’s wastewater treatment plant (WTP) as well as lake water and sediment samples obtained close to the WTP outlet pipe and a remote site close to a drinking water pump were evaluated for the prevalence of MRB. Selected isolates were identified (16S rRNA gene fragment sequencing) and characterized with regards to further resistances, resistance genes, and plasmids. Mostly, studies investigating this issue have relied on cultivation-based approaches. However, the limitations of these tools are well known, in particular for environmental microbial communities, and cultivation-independent molecular tools should be applied in parallel in order to take non-culturable organisms into account. Here we directly quantified the sulfonamide resistance genes sul1 and sul2 from environmental DNA extracts using TaqMan real-time quantitative PCR. Hospital sewage contained the highest load of MRB and antibiotic resistance genes (ARGs). Wastewater treatment reduced the total bacterial load up to 78% but evidence for selection of extremely multiresistant strains and accumulation of resistance genes was observed. Our data clearly indicated pollution of sediments with ARGs in the vicinity of the WTP outlet. The potential of lakes as reservoirs of MRB and potential risks are discussed

Orometric methods in bounded metric data

A large amount of data accommodated in knowledge graphs (KG) is metric. For example, the Wikidata KG contains a plenitude of metric facts about geographic entities like cities or celestial objects. In this paper, we propose a novel approach that transfers orometric (topographic) measures to bounded metric spaces. While these methods were originally designed to identify relevant mountain peaks on the surface of the earth, we demonstrate a notion to use them for metric data sets in general. Notably, metric sets of items enclosed in knowledge graphs. Based on this we present a method for identifying outstanding items using the transferred valuations functions isolation and prominence. Building up on this we imagine an item recommendation process. To demonstrate the relevance of the valuations for such processes, we evaluate the usefulness of isolation and prominence empirically in a machine learning setting. In particular, we find structurally relevant items in the geographic population distributions of Germany and France. © 2020, The Author(s)

Evidence from clinical trials on high-risk medical devices in children

BACKGROUND: Meeting increased regulatory requirements for clinical evaluation of medical devices marketed in Europe in accordance with the Medical Device Regulation (EU 2017/745) is challenging, particularly for high-risk devices used in children. METHODS: Within the CORE-MD project, we performed a scoping review on evidence from clinical trials investigating high-risk paediatric medical devices used in paediatric cardiology, diabetology, orthopaedics and surgery, in patients aged 0–21 years. We searched Medline and Embase from 1st January 2017 to 9th November 2022. RESULTS: From 1692 records screened, 99 trials were included. Most were multicentre studies performed in North America and Europe that mainly had evaluated medical devices from the specialty of diabetology. Most had enrolled adolescents and 39% of trials included both children and adults. Randomized controlled trials accounted for 38% of the sample. Other frequently used designs were before-after studies (21%) and crossover trials (20%). Included trials were mainly small, with a sample size <100 participants in 64% of the studies. Most frequently assessed outcomes were efficacy and effectiveness as well as safety. CONCLUSION: Within the assessed sample, clinical trials on high-risk medical devices in children were of various designs, often lacked a concurrent control group, and recruited few infants and young children

Left ventricular scar and the acute hemodynamic effects of multivein and multipolar pacing in cardiac resynchronization

Background We sought to determine whether presence, amount and distribution of scar impacts the degree of acute hemodynamic response (AHR) with multisite pacing. Multi-vein pacing (MVP) or multipolar pacing (MPP) with a multi-electrode left ventricular (LV) lead may offer benefits over conventional biventricular pacing in patients with myocardial scar. Methods In this multi-center study left bundle branch block patients underwent an hemodynamic pacing study measuring LV dP/dtmax. Patients had cardiac magnetic resonance scar imaging to assess the effect of scar presence, amount and distribution on AHR. Results 24 patients (QRS 171 ± 20 ms) completed the study (83% male). An ischemic etiology was present in 58% and the mean scar volume was 6.0 ± 7.0%. Overall discounting scar, MPP and MVP showed no significant AHR increase compared to an optimized “best BiV” (BestBiV) site. In a minority of patients (6/24) receiver-operator characteristic analysis of scar volume (cut off 8.48%) predicted a small AHR improvement with MPP (sensitivity 83%, specificity 94%) but not MVP. Patients with scar volume > 8.48% had a MPP-BestBiV of 3 ± 6.3% vs. −6.4 ± 7.7% for those below the cutoff. There was a significant correlation between the difference in AHR and scar volume for MPP-BestBiV (R = 0.49, p = 0.02) but not MVP-BestBiV(R = 0.111, p = 0.62). The multielectrode lead positioned in scar predicted MPP AHR improvement (p = 0.04). Conclusions Multisite pacing with MPP and MVP shows no AHR benefit in all-comers compared to optimized BestBiV pacing. There was a minority of patients with significant scar volume in relation to the LV site that exhibited a small AHR improvement with MPP

Evidence from clinical trials on high-risk medical devices in children: a scoping review

Background Meeting increased regulatory requirements for clinical evaluation of medical devices marketed in Europe in accordance with the Medical Device Regulation (EU 2017/745) is challenging, particularly for high-risk devices used in children. Methods Within the CORE-MD project, we performed a scoping review on evidence from clinical trials investigating high-risk paediatric medical devices used in paediatric cardiology, diabetology, orthopaedics and surgery, in patients aged 0–21 years. We searched Medline and Embase from 1st January 2017 to 9th November 2022. Results From 1692 records screened, 99 trials were included. Most were multicentre studies performed in North America and Europe that mainly had evaluated medical devices from the specialty of diabetology. Most had enrolled adolescents and 39% of trials included both children and adults. Randomized controlled trials accounted for 38% of the sample. Other frequently used designs were before-after studies (21%) and crossover trials (20%). Included trials were mainly small, with a sample size <100 participants in 64% of the studies. Most frequently assessed outcomes were efficacy and effectiveness as well as safety. Conclusion Within the assessed sample, clinical trials on high-risk medical devices in children were of various designs, often lacked a concurrent control group, and recruited few infants and young children

European Expert Opinion on ANT-DBS therapy for patients with drug-resistant epilepsy (a Delphi consensus)

Introduction: Although deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) represents an established third-line therapy for patients with drug-resistant focal epilepsy, guiding reports on practical treatment principles remain scarce. Methods: An Expert Panel (EP) of 10 European neurologists and 4 neurosurgeons was assembled to share their experience with ANT-DBS therapy. The process included a review of the current literature, which served as a basis for an online survey completed by the EP prior to and following a face-to-face meeting (Delphi method). An agreement level of >= 71 % was considered as consensus. Results: Out of 86 reviewed studies, 46 (53 %) were selected to extract information on the most reported criteria for patient selection, management, and outcome. The Delphi process yielded EP consensus on 4 parameters for selection of good candidates and patient management as well as 7 reasons of concern for this therapy. Since it was not possible to give strict device programming advice due to low levels of evidence, the experts shared their clinical practice: all of them start with monopolar stimulation, 79 % using the cycling mode. Most (93 %) EP members set the initial stimulation frequency and pulse width according to the SANTE parameters, while there is more variability in the amplitudes used. Further agreement was achieved on a list of 7 patient outcome parameters to be monitored during the follow-up. Conclusions: Although current evidence is too low for definite practical guidelines, this EP report could support the selection and management of patients with ANT-DBS

EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA); Scientific Opinion on establishing Food-Based Dietary Guidelines

This Opinion of the EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA) provides guidance on the translation of nutrient based dietary advice into guidance, intended for the European population as a whole, on the contribution of different foods or food groups to an overall diet that would help to maintain good health through optimal nutrition (food-based dietary guidelines). The main focus of this Opinion is put on the scientific process of developing food-based dietary guidelines (FBDG) for the diverse European populations, following a stepwise approach which should ideally consist of: 1) Identification of diet-health relationships, 2) Identification of country specific diet-related health problems, 3) Identification of nutrients of public health importance, 4) Identification of foods relevant for FBDG, 5) Identification of food consumption patterns, 6) Testing and optimising FBDG and 7) Graphical representations of FBDG. FBDG should focus on the diet-disease relationships of particular relevance to the specific population and should be developed using a multi-disciplinary approach. The early involvement of stakeholders is recommended to promote the acceptance of the outcome. FBDG should be consistent with other public policies that have an impact on food availability and be integrated with other policies related to health promotion. Once established, FBDG should be implemented and their impact monitored and evaluate

Scientific Opinion on the substantiation of a health claim related to fermented milk containing Lactobacillus casei DN-114 001 plus yoghurt symbiosis (Actimel\uae), and reduction of Clostridium difficile toxins in the gut of patients receiving antibiotics and reduced risk of acute diarrhoea in patients receiving antibiotics pursuant to Article 14 of Regulation (EC) No 1924/2006

Following an application from Danone Produits Frais France submitted pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of France, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver an opinion on the scientific substantiation of a health claim related to a fermented milk drink Actimel\uae containing Lactobacillus casei (Lc) DN-114 001 and reduction of the presence of Clostridium difficile toxins in the gut which reduces the incidence of acute diarrhoea. The Panel considers that the food constituent, Actimel\uae, which is the subject of the health claim, is sufficiently characterised. The Panel considers that reducing the risk of Clostridium difficile diarrhoea by reducing the presence of C. difficile toxins is a beneficial physiological effect. In total the applicant indicated seven publications on human studies, three unpublished human studies, eight published and one unpublished non-human studies to be pertinent for the claimed effect. In weighing the evidence, the Panel took into account that human and animal studies showed partial survival of Lc DN-114 001 during its gastrointestinal passage, that one human intervention study with Actimel\uae which showed a statistically significant risk reduction for CDAD had considerable limitations, that there were only limited data on the effect of Actimel\uae on the reduction C. difficile toxins (the risk factor) in humans, that one study which showed an inhibitory effect of Lc DN-114 001 on the growth of C. difficile in vitro does not predict the occurrence of an effect against C. difficile in humans, that five further human studies do not support the proposed mechanisms by which Actimel\uae could exert the claimed effect, and that the evidence provided from a further two animal and three in vitro studies does not establish that effects of Actimel\uae or Lc DN-114 001 in these model systems related to immune function and infection can predict the occurrence of such effects in humans. The Panel concludes that the evidence provided is insufficient to establish a cause and effect relationship between the consumption of Actimel\uae and a reduction of the risk of C. difficile diarrhoea by reducing the presence of C. difficile toxins

Scientific opinion on the substantiation of health claims related to olive oil and maintenance of normal blood LDL-cholesterol concentrations (ID 1316, 1332), maintenance of normal (fasting) blood concentrations of triglycerides (ID 1316, 1332), maintenance of normal blood HDL-cholesterol concentrations (ID 1316, 1332) and maintenance of normal blood glucose concentrations (ID 4244) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006. This opinion addresses the scientific substantiation of health claims in relation to olive oil and maintenance of normal blood LDL-cholesterol concentrations, maintenance of normal (fasting) blood concentrations of triglycerides, maintenance of normal blood HDL-cholesterol concentrations and maintenance of normal blood glucose concentrations. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims and references that EFSA has received from Member States or directly from stakeholders. The food that is the subject of the health claims is olive oil. The Panel considers that olive oil is sufficiently characterised in relation to the claimed effect