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Objectives:Most people living with HIV stay sexually active, but some remain inactive. This study investigated prevalence and correlates of sexual inactivity among European HIV-positive men who have sex with men (MSM).Methods:An anonymous sexual health questionnaire was distributed in 17 HIV outpatient clinics throughout Europe. Ninety-seven (11.6%) of 838 respondents reported absence of sexual activity.Results:Multivariable regression analysis identified older age, relationship status, and less satisfaction with general health and sexual desire as being associated with sexual inactivity.Conclusions:Prevalence of sexual inactivity has declined since the introduction of antiretroviral therapy to levels similar to those of HIV-negative MSM, suggesting a tendency toward normalization of HIV-positive MSM's sex lives. [ABSTRACT FROM AUTHOR]

In Europe, the reduction of acute care hospital beds has been one of the measures implemented to restrict hospital expenditure. The aim of this study is to gain insight into the effect bed reductions have on the use of the remaining beds within different healthcare systems. We concentrated on two healthcare system elements: hospital financing system (per diem and global budget systems) and physician remuneration system (fee-for-service and salary systems). We also controlled for technological development and demand for healthcare. We used data from the OECD health data files of 10 North-Western European countries on hospital bed supply and use. The hospital bed indicators used were occupancy rate, average length of stay and admission rate. The data were analysed with multilevel analysis. We found some indication that the different financial incentives of hospital financing systems do indeed influence hospital bed use in the case of reductions in acute care hospital bed supply in different ways. However, we found significant effects only for the hospital bed use indicators “occupancy rate” and “admission rate”. For physician financing systems, no significant effects were found. [Copyright &y& Elsevier]

This article asks two questions: first, why are party voters less favourable towards specific EU policies than party elites?; second, how does political representation of EU preferences actually work, is it an elite- or a mass-driven process? The data-sets of the European Election Studies 1979 and 1994 are analysed which involve both an elite and a mass survey component. In contrast to earlier research, it appears that political representation of EU preferences works rather well regarding the grand directions of policy making, and that party elites behave responsively in view of changing EU preferences among their voters. [ABSTRACT FROM AUTHOR]

Both the Netherlands and other European countries are involved in the transition from a breadwinner society towards a more individual-oriented society. What is unique in the Dutch case is the strong emphasis on the equal sharing of time, between paid and unpaid work as well as between women and men. Despite the preferences among citizens for a more equal sharing of paid and unpaid work, in practice it appears that general participation in paid labour is being achieved more rapidly than general participation in unpaid labour. The article looks at the obstacles and sticking points which stand in the way of the process of redistribution and investigates how this process can be accelerated. It includes an empirical analysis on survey data for the Netherlands with respect to both actual and preferred working hours for married and cohabitating men and women. The authors conclude that a consistent government policy is lacking. As a consequence neither individuals nor organizations get signals that might contribute to those steps in the area of part-time work, child-care provision and leave facilities that would bring about a redistribution of paid and unpaid work between women and men. [ABSTRACT FROM AUTHOR]

Background & Aims: Conventional endoscopic mucosal resection (C-EMR) is established as the primary treatment modality for superficial nonampullary duodenal epithelial tumors (SNADETs), but recently underwater endoscopic mucosal resection (U-EMR) has emerged as a potential alternative. The majority of previous studies focused on Asian populations and small lesions (≤20 mm). We aimed to compare the efficacy and outcomes of U-EMR vs C-EMR for SNADETs in a Western setting., Methods: This was a retrospective multinational study from 10 European centers that performed both C-EMR and U-EMR between January 2013 and July 2023. The main outcomes were the technical success, procedure-related adverse events (AEs), and the residual/recurrent adenoma (RRA) rate, evaluated on a per-lesion basis. We assessed the association between the type of endoscopic mucosal resection and the occurrence of AEs or RRAs using mixed-effects logistic regression models (propensity scores). Sensitivity analyses were performed for lesions ≤20 mm or >20 mm., Results: A total of 290 SNADETs submitted to endoscopic resection during the study period met the inclusion criteria and were analyzed (C-EMR: n = 201, 69.3%; U-EMR: n = 89, 30.7%). The overall technical success rate was 95.5% and comparable between groups. In logistic regression models, compared with U-EMR, C-EMR was associated with a significantly higher frequency of overall delayed AEs (odds ratio [OR], 4.95; 95% CI, 2.87-8.53), postprocedural bleeding (OR, 7.92; 95% CI, 3.95-15.89), and RRAs (OR, 3.66; 95% CI, 2.49-5.37). Sensitivity analyses confirmed these results when solely considering either small (≤20 mm) or large (>20 mm) lesions., Conclusions: Compared with C-EMR, U-EMR was associated with a lower rate of overall AEs and RRAs, regardless of lesion size. Our results confirm the possible role of U-EMR as an effective and safe technique in the management of SNADETs., (Copyright © 2025 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: The 313-variant polygenic risk score (PRS 313 ) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS 313 across different European populations which could influence risk estimation has not been performed., Methods: We explored the distribution of PRS 313 across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank. The mean PRS was calculated by country in the BCAC dataset and by country of birth in the UK Biobank. We explored different approaches to reduce the observed heterogeneity in the mean PRS across the countries, and investigated the implications of the distribution variability in risk prediction., Results: The mean PRS 313 differed markedly across European countries, being highest in individuals from Greece and Italy and lowest in individuals from Ireland. Using the overall European PRS 313 distribution to define risk categories, leads to overestimation and underestimation of risk in some individuals from these countries. Adjustment for principal components explained most of the observed heterogeneity in the mean PRS. The mean estimates derived when using an empirical Bayes approach were similar to the predicted means after principal component adjustment., Conclusions: Our results demonstrate that PRS distribution differs even within European ancestry populations leading to underestimation or overestimation of risk in specific European countries, which could potentially influence clinical management of some individuals if is not appropriately accounted for. Population-specific PRS distributions may be used in breast cancer risk estimation to ensure predicted risks are correctly calibrated across risk categories., Competing Interests: Declarations. Ethics approval and consent to participate: All study participants gave written informed consent, and all the Breast Cancer Association Consortium studies were approved by the relevant ethics committees. The Breast Cancer Association Consortium data have been used under the application with access number 712. The use of the UK Biobank has been approved under application ID102655. Consent for publication: Not applicable. Competing interests: The following authors declare conflicts not directly relevant to this work as stated below: U.M. has a patent (no: EP10178345.4) for Breast Cancer Diagnostics and held personal shares in Abcodia Ltd between 2011 and 2021. She has research collaborations with Mercy Bioanalytics, iLOF, RNA Guardian and Micronoma in the field of early detection of cancer. P.A.F. conducts research funded by Amgen, Novartis and Pfizer. He received Honoraria from Roche, Novartis and Pfizer. R.A.M. is a Consultant for Pharmavite., (© 2024. The Author(s).)

Background: Treatment of patients with in-stent restenosis (ISR) remains challenging. In this setting the use of drug-coated balloons (DCB) represents an attractive approach to avoid adding another metal layer to the coronary wall., Aims: The Chansu Vascular Technologies (CVT)-ISR trial aimed to evaluate the safety and efficacy of a novel everolimus-DCB (CVT-DCB) using a new coating formulation and crystalline everolimus., Methods: The CVT-ISR trial was a prospective, multicenter, open, single-arm, first-in-man (FIM) study. A total of 51 patients (mean age 69.2 years, 74.5% male) with single ISR coronary lesions (≤24 mm in length) were enrolled at nine sites in Europe., Results: The primary safety endpoint, freedom from target lesion failure (TLF) at 180 days, was 92.2%, with the lower bound of the 95% confidence interval (81.1%), above the protocol-defined objective performance criterion (OPC) (65% for conventional balloon angioplasty, P  < 0.05). At 1 year freedom from TLF was 90.2%. The primary efficacy endpoint, in-stent late lumen loss at 180 days (evaluated in a predefined subgroup of 25 patients scheduled for late angiography), was 0.40 mm (median 0.30 mm), lower than the protocol-defined OPC of the plain balloon angioplasty historical control (0.80 mm, P  < 0.001)., Conclusion: This FIM study demonstrated the superior efficacy of the new everolimus CVT-DCB compared with conventional balloon angioplasty in the treatment of patients with ISR., Clinical Trials Registration: NCT05731700., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Plastic pollution has become a global concern, affecting many species around the world. While well-documented for marine ecosystems, the impact of plastic pollution on terrestrial ecosystems is comparatively limited. In fact, only recently have some studies begun to explore the occurrence, pathways, and impacts of plastic in the atmosphere and on terrestrial species. Here, we assess the presence of synthetic material in nests of three swift species breeding in the Western Palearctic: the common swift (Apus apus), the pallid swift (Apus pallidus), and the alpine swift (Tachymarptis melba). Using data from 487 nests spanning 25 colonies and seven European countries, we show that 36.5 % of the examined nests contained anthropogenic materials, mainly plastic debris. Notably, Pallid swifts' nests, with 85 % of the total nests examined with plastic, rank among birds with the highest plastic content in nests. We also demonstrate that the probability of finding plastic in the nest increased substantially with the human footprint of the landscape. Last, we recorded four cases of swifts entangled in their own nest, a low proportion compared to other species studied previously. Our study provides compelling evidence that plastic pollution may also be considered a concern for other terrestrial species, particularly for birds with highly aerial lifestyles, such as other swifts. The correlation with the human footprint suggests that areas with higher human activity contribute more significantly. Moreover, the entanglement cases, although low, indicate a threat to bird health and welfare. To our knowledge, our study is the first to report a direct interaction between floating plastic debris in the atmosphere and any species. Understanding this interaction is key, not only due to the lack of research on the topic, but also because it highlights that plastic pollution is a multifaceted environmental issue affecting various ecosystem categories, and the broader implications of atmospheric plastic circulation on wildlife and ecosystems health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Non-invasive biomarkers are promising tools for improving kidney allograft rejection monitoring, but their clinical adoption requires more evidence in specifically designed studies. To address this unmet need, we designed the EU-TRAIN study, a large prospective multicentric unselected cohort funded by the European Commission. Here, we included consecutive adult patients who received a kidney allograft in nine European transplant centers between November 2018 and June 2020. We prospectively assessed gene expression levels of 19 blood messenger RNAs, four antibodies targeting non-human leukocyte antigen (HLA) endothelial antigens, together with circulating anti-HLA donor-specific antibodies (DSA). The primary outcome was allograft rejection (antibody-mediated, T cell-mediated, or mixed) in the first year post-transplantation. Overall, 412 patients were included, with 812 biopsies paired with a blood sample. CD4 gene expression was significantly associated with rejection, while circulating anti-HLA DSA had a significant association with allograft rejection and a strong association with antibody-mediated rejection. All other tested biomarkers, including AKR1C3, CD3E, CD40, CD8A, CD9, CTLA4, ENTPD1, FOXP3, GZMB, ID3, IL7R, MS4A1, MZB1, POU2AF1, POU2F1, TCL1A, TLR4, and TRIB1, as well as antibodies against angiotensin II type 1 receptor, endothelin 1 type A receptor, C3a and C5a receptors, did not show significant associations with allograft rejection. The blood messenger RNAs and non-HLA antibodies did not show an additional value beyond standard of care monitoring parameters and circulating anti-HLA DSA to predict allograft rejection in the first year post-transplantation. Thus, our results open avenues for specifically designed studies to demonstrate the clinical relevance and implementation of other candidate non-invasive biomarkers in kidney transplantation practice., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Objectives: The study examines the impact of changes on dental education and practice in Europe, including the development of new practice models such as investor-owned dental centers and practice chains., Method and Materials: This study aimed to collect and critically examine data regarding the care environment, education, and organizational structures of the dental profession across European Regional Organization of the FDI World Dental Federation (ERO) member states and other countries in the World Health Organization European region. A questionnaire from the ERO was used., Results: National dental associations across 45 countries participated. An average of 1,459.79 (SD ± 800.80) inhabitants per dental practitioner was found, with independent practices being the most prevalent form of dental practice (48.65% ± 28.28%) followed by employment in private practice (24.32% ± 20.33%), and joint practices (15.27% ± 20.39%). There are statistically significantly more state universities than private universities (P .01); the percentage of females attending dental schools was statistically significantly higher than males (P .01). Two-thirds of the participating countries (n = 30, 66.67%) have legal frameworks allowing various stakeholders, including investors, and local communities, to establish dental health care centers., Conclusions: The findings highlight the evolving landscape of the dental profession in Europe and its regulatory context. There is a clear need for ongoing evaluations and adjustments in educational and practice frameworks to ensure and maintain high-quality oral health care. Future research should delve into the various professional dental practice forms and incorporate qualitative, care-related, and patient-centered considerations for a more thorough understanding of Europe's oral health care dynamics. (Quintessence Int 2024;55:744-755; doi: 10.3290/j.qi.b5714883).

Investigator-initiated clinical studies (IICSs), also referred to as non-commercial, academic or independent clinical studies, address important research questions that are usually neglected by industry despite their high societal value. Indeed, industry may direct their focus and resources on studies that will yield results and products that can ultimately generate revenue for the company. Conversely, IICS research questions include (a) refining or getting new indications of available treatments (drug repurposing); (b) optimisation, by comparing various health products or treatment regimens; and (c) innovation, especially for advanced therapies. Multinational IICSs increase the scientific quality of the data by exchange of research ideas, scientific techniques and tools. Participation of patients from different geographical, social and ethnic backgrounds equally adds to the value of study results and yields more generalisable evidence than a study confined to a single geographical location. Multinational IICSs are generally sponsored by non-profit/academic organisations and publicly funded. Funding has been already identified as a main challenge for the conduct IICS and especially for clinical trials (IICTs, IICS where a medical intervention is directly tested). Main barriers to the conduct of multinational IICTs with public funding include: Limitations of budget and duration of the eligibility of costs Lack of flexibility to move funds transnationally Tendering rules Complexity in the reporting of the eligible costs to funders We describe why there is a need to support multinational IICS, what should be their objectives and what are the current funding mechanisms in Europe. Strategies for funding multinational IICS should evolve to mitigate identified barriers, thus facilitating research that can provide answers to highly relevant questions in healthcare which are less likely to be answered by studies funded by the pharmaceutical and medical device industry., (© 2024. The Author(s).)

Purpose: The purpose of the European consensus was to provide recommendations for the treatment of patients with a painful degenerative varus knee using a joint preservation approach. Part II focused on surgery, rehabilitation and complications after tibial or femoral correction osteotomy., Methods: Ninety-four orthopaedic surgeons from 24 countries across Europe were involved in the consensus, which focused on osteotomies around the knee. The consensus was performed according to the European Society for Sports Traumatology, Knee Surgery and Arthroscopy consensus methodology. The steering group designed the questions and prepared the statements based on the experience of the experts and the evidence of the literature. The statements were evaluated by the ratings of the peer-review groups before a final consensus was released., Results: The ideal hinge position for medial opening wedge high tibial osteotomy (MOW HTO) should be at the upper level of the proximal tibiofibular joint, and for lateral closing wedge distal femoral osteotomy (LCW DFO) just above the medial femoral condyle. Hinge protection is not mandatory. Biplanar osteotomy cuts provide more stability and quicker bony union for both MOW HTO and LCW DFO and are especially recommended for the latter. Osteotomy gap filling is not mandatory, unless structural augmentation for stability is required. Patient-specific instrumentation should be reserved for complex cases by experienced hands. Early full weight-bearing can be adopted after osteotomy, regardless of the technique. However, extra caution should be exercised in DFO patients. Osteotomy patients should return to sports within 6 months., Conclusion: Clear recommendations for surgical strategy, rehabilitation and complications of knee osteotomies for the painful degenerative varus knee were demonstrated. In Part 2 of the consensus, high levels of agreement were reached by experts throughout Europe, under variable working conditions. Where science is limited, the collated expertise of the collaborators aimed at providing guidance for orthopaedic surgeons developing an interest in the field and highlighting areas for potential future research., Level of Evidence: Level II, consensus., (© 2024 The Author(s). Knee Surgery, Sports Traumatology, Arthroscopy published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Background and Aims: Management of Budd-Chiari syndrome (BCS) has improved over the last decades. The main aim was to evaluate the contemporary post-liver transplant (post-LT) outcomes in Europe., Approach and Results: Data from all patients who underwent transplantation from 1976 to 2020 was obtained from the European Liver Transplant Registry (ELTR). Patients < 16 years, with secondary BCS or HCC were excluded. Patient survival (PS) and graft survival (GS) before and after 2000 were compared. Multivariate Cox regression analysis identified predictors of PS and GS after 2000. Supplemental data was requested from all ELTR-affiliated centers and received from 44. In all, 808 patients underwent transplantation between 2000 and 2020. One-, 5- and 10-year PS was 84%, 77%, and 68%, and GS was 79%, 70%, and 62%, respectively. Both significantly improved compared to outcomes before 2000 ( p < 0.001). Median follow-up was 50 months and retransplantation rate was 12%. Recipient age (aHR:1.04,95%CI:1.02-1.06) and MELD score (aHR:1.04,95%CI:1.01-1.06), especially above 30, were associated with worse PS, while male sex had better outcomes (aHR:0.63,95%CI:0.41-0.96). Donor age was associated with worse PS (aHR:1.01,95%CI:1.00-1.03) and GS (aHR:1.02,95%CI:1.01-1.03). In 353 patients (44%) with supplemental data, 33% had myeloproliferative neoplasm, 20% underwent TIPS pre-LT, and 85% used anticoagulation post-LT. Post-LT anticoagulation was associated with improved PS (aHR:0.29,95%CI:0.16-0.54) and GS (aHR:0.48,95%CI:0.29-0.81). Hepatic artery thrombosis and portal vein thrombosis (PVT) occurred in 9% and 7%, while recurrent BCS was rare (3%)., Conclusions: LT for BCS results in excellent patient- and graft-survival. Older recipient or donor age and higher MELD are associated with poorer outcomes, while long-term anticoagulation improves both patient and graft outcomes., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Purpose: The European consensus was designed with the objective of combining science and expertise to produce recommendations that would educate and provide guidance in the treatment of the painful degenerative varus knee. Part I focused on indications and planning., Methods: Ninety-four orthopaedic surgeons from 24 European countries were involved in the consensus, which focused on the most common indications for osteotomy around the knee. The consensus was performed according to an established ESSKA methodology. The questions and recommendations made were initially designed by the consensus steering group. And 'best possible' answers were provided based upon the scientific evidence available and the experience of the experts. The statements produced were further evaluated by ratings and peer review groups before a final consensus was reached., Results: There is no reliable evidence to exclude patients based on age, gender or body weight. An individualised approach is advised; however, cessation of smoking is recommended. The same applies to lesser degrees of patellofemoral and lateral compartment arthritis, which may be accepted in certain situations. Good-quality limb alignment and knee radiographs are a mandatory requirement for planning of osteotomies, and Paley's angles and normal ranges are recommended when undertaking deformity analysis. Emphasis is placed upon the correct level at which correction of varus malalignment is performed, which may involve double-level osteotomy. This includes recognition of the importance of individual bone morphology and the maintenance of a physiologically appropriate joint line orientation., Conclusion: The indications of knee osteotomies for painful degenerative varus knees are broad. Part I of the consensus highlights the versatility of the procedure to address multiple scenarios with bespoke planning for each case. Deformity analysis is mandatory for defining the bone morphology, the site of the deformity and planning the correct procedure., Level of Evidence: Level II, consensus., (© 2024 The Authors. Knee Surgery, Sports Traumatology, Arthroscopy published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Due to its intrinsic complexity and the principle of collective solidarity that governs it, solid organ transplantation (SOT) seems to have been spared from the increase in litigation related to medical activity. Litigation relating to solid organ transplantation that took place in the 29 units of the Assistance Publique-Hôpitaux de Paris and was the subject of a judicial decision between 2015 and 2022 was studied. A total of 52 cases of SOT were recorded, all in adults, representing 1.1% of all cases and increasing from 0.71% to 1.5% over 7 years. The organs transplanted were 25 kidneys (48%), 19 livers (37%), 5 hearts (9%) and 3 lungs (6%). For kidney transplants, 11 complaints (44%) were related to living donor procedures and 6 to donors. The main causes of complaints were early post-operative complications in 31 cases (60%) and late complications in 13 cases (25%). The verdicts were in favour of the institution in 41 cases (79%). Solid organ transplants are increasingly the subject of litigation. Although the medical institution was not held liable in almost 80% of cases, this study makes a strong case for patients, living donors and their relatives to be better informed about SOT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Belghiti, Cauchy, Antoine, Cheron and Matignon.)

Background: The European Society of Plastic, Reconstructive and Aesthetic Surgery (ESPRAS) comprises 40 national societies across Europe. In addition to ESPRAS, there are 8 different European Plastic Surgery societies representing Plastic Surgeons in Europe. The 4 th European Leadership Forum (ELF) of ESPRAS, held under the motto "Stronger together in Europe" in Munich in 2023, aimed to collect and disseminate information regarding the national member societies of ESPRAS and European societies for Plastic Surgeons. The purpose was to identify synergies and redundancies and promote improved cooperation and exchange to enhance coordinated decision-making at the European level., Material and Methods: An online survey was conducted regarding the organisational structures, objectives and challenges of national and European societies for Plastic Surgeons in Europe. This survey was distributed to official representatives (Presidents, Vice Presidents and General Secretaries) and delegates of national and European societies at the ELF meeting. Missing information was completed using data obtained from the official websites of the respective European societies. Preliminary results were discussed during the 4 th ELF meeting in Munich in March 2023., Results: The ESPRAS survey included 22 national and 9 European Plastic Surgery societies representing more than 7000 Plastic Surgeons in Europe. Most national societies consist of less than 500 full members (median 182 members (interquartile range (IQR) 54-400); n=22). European societies, which covered the full spectrum or subspecialities, differed in membership types and congress cycles, with some requiring applications by individuals and others including national societies. The main purposes of the societies include research, representation against other disciplines, specialisation and education as well as more individual goals like patient care and policy regulation., Conclusion: This ESPRAS survey offers key insights into the structures, requirements and challenges of national and European societies for Plastic Surgeons, highlighting the relevance of ongoing close exchange between the societies to foster professional advancement and reduce redundancies. Future efforts of the ELF will continue to further explore strategies for enhancing collaboration and harmonisation within the European Plastic Surgery landscape., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Theories from anthropology, evolutionary psychology, and sociology have focused on the potential adaptive benefits of hobby engagement for mental health in older adults. However, previous studies have used data from single countries, potentially biased by specific measurement and methodological approaches, cohort effects, or cultural specificities. Whether there are genuine benefits for mental health in older adults cross-culturally remains unknown. This study explored the consistency of this association across 16 different nations., Methods: For this epidemiological study, we used data from adults aged 65 years or older across 16 countries in the USA, Europe, and Asia, represented in five longitudinal studies (ELSA, JAGES, HRS, SHARE and CHARLS; N=93 263, 45-62% female, mean age 72-76 years, data collected 2008-20). We harmonised measures of self-reported engagement in hobbies and past-times, depressive symptoms (validated scales), and Likert scale responses for self-reported health, happiness, and life satisfaction. We conducted fixed-effects models and longitudinal regression models of hobbies and mental health for each country and then pooled in multinational meta-analyses. We accounted for all time-constant factors including those unobserved (eg, genetics, past leisure behaviour, medical history, psychological traits) and identified time-varying factors (eg, sociodemographic background, clinical conditions, daily functioning). We tested the potential moderating effects of country-level determinants of health in meta-regressions and multilevel models., Findings: Meta-analytic fixed-effects findings showed that having a hobby was associated with fewer depressive symptoms (pooled coefficient -0·10, 95% CI -0·13 to -0·07, I 2 =69·5%, H 2 =3·28), and higher levels of self-reported health (0·06, 0·03 to 0·08, I 2 =48·1%, H 2 =1·93), happiness (0·09, 0·06 to 0·13, I 2 =67·0%, H 2 =3·03), and life satisfaction (0·10, 0·08 to 0·12, I 2 =33·6%, H 2 =1·51). Results were consistent in meta-analyses of longitudinal regression models testing directionality of findings. Macro-level factors such as life expectancy, world happiness index, country wealth, and income inequality predicted prevalence of hobby engagement, but they showed only marginal moderating effects on the association between hobbies and mental health., Interpretation: Despite some heterogeneity in measurement between the cohorts, the apparent universality of the health benefits of hobbies internationally suggests that facilitating greater opportunities for engagement across demographic groups and between countries could be an important part of multidisciplinary care. Findings have implications for social prescribing schemes (currently in trial in many countries) and multidisciplinary work on origins and human behavioural patterns of hobby engagement., Funding: National Endowment for the Arts, Wellcome Trust, Belgian Nnational Scientific Fund (FNRS)., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In rural areas, nitrate concentrations in surface waters most often originate from the leaching of excess N fertilizer in agricultural lands, whereas forested catchments often have good water quality. However, Douglas-fir plantations may induce nitrogen cycle unbalances which may lead to an excess of nitrate production in the soil. We hypothesize that the excess of production of nitrate in the soil and nitrate leaching to streamwater is greater in catchments planted with Douglas fir. We used paired catchments in both France and Luxembourg with different land covers (Douglas-fir, Spruce, Deciduous, Grassland and clearcut) which were monitored over a 3-5 year period in order to assess the effect of Douglas-fir plantations on the chemical composition of surface water. Nitrate concentration in the soil and groundwater were also monitored. The results show that nitrate concentrations in streams draining Douglas-fir catchments were two to ten times higher than in streams draining other land covers, but were similar to the clearcut catchment. Nitrate concentrations under Douglas-fir in groundwater (up to 50 mg L -1 ) and in the soil were also higher than under all other land covers. Soil nitrate concentration was related to stream nitrate concentration. This suggests that soil processes, through excessive nitrate production under Douglas-fir, are driving the nitrate concentration in the stream water and our hypothesis of a transfer of a fairly large proportion of this excessive production from the soil to the stream is supported. This study also shows that nitrate concentrations in surface and ground waters in rural areas could also originate from Douglas fir forested catchments. The impact of Douglas-fir is nevertheless reduced downstream through a dilution effect: mixing tree species at the catchment scale could thus be a solution to mitigate the effect of Douglas-fir on nitrate concentration in surface waters., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: The predominance of the psychodynamic approach is often put forward to explain the delay in diagnosis and treatment of attention-deficit disorder with hyperactivity (ADHD) reported in France., Objective: A bibliometric study of abstracts, articles, or letters authored by French researchers may provide objective insight into this issue., Methods: Online electronic databases were searched without any date limits for documents related to ADHD, and allocated to the AllFR group when all authors had an affiliation in France or to the notAllFR group when at least one author had an affiliation in France. Publications expressing any psychodynamic point of view on the causes and/or treatment of ADHD were identified., Results: A total of 747 documents were analyzed: 417 were exclusively indexed in SCOPUS, and 418 were allocated to the AllFR group. Compared with documents in the notAllFR group, documents in the AllFR group were written by a smaller number of authors (median 3 vs. 6, p<0.002), more frequently evoked psychodynamic concepts (10.45% vs. 1.67%, p<0.001), and less frequently acknowledged the persistence of ADHD in adulthood (29.10% vs. 42.14%). The psychodynamic approach was likely to rely on case reports of fewer than three children., Conclusions: Any serious review of the literature should pool documents from several online databases, especially SCOPUS. In publications by only French authors, the psychodynamic approach seems predominant and the persistence of ADHD in adulthood is overlooked. This may concur with the excessive delay observed in the diagnosis and treatment of children and adults in France compared to other European countries., (Copyright © 2023 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Although the value of patient and public involvement and engagement (PPIE) activities in the development of new interventions and tools is well known, little guidance exists on how to perform these activities in a meaningful way. This is particularly true within large research consortia that target multiple objectives, include multiple patient groups, and work across many countries. Without clear guidance, there is a risk that PPIE may not capture patient opinions and needs correctly, thereby reducing the usefulness and effectiveness of new tools. Mobilise-D is an example of a large research consortium that aims to develop new digital outcome measures for real-world walking in 4 patient cohorts. Mobility is an important indicator of physical health. As such, there is potential clinical value in being able to accurately measure a person's mobility in their daily life environment to help researchers and clinicians better track changes and patterns in a person's daily life and activities. To achieve this, there is a need to create new ways of measuring walking. Recent advancements in digital technology help researchers meet this need. However, before any new measure can be used, researchers, health care professionals, and regulators need to know that the digital method is accurate and both accepted by and produces meaningful outcomes for patients and clinicians. Therefore, this paper outlines how PPIE structures were developed in the Mobilise-D consortium, providing details about the steps taken to implement PPIE, the experiences PPIE contributors had within this process, the lessons learned from the experiences, and recommendations for others who may want to do similar work in the future. The work outlined in this paper provided the Mobilise-D consortium with a foundation from which future PPIE tasks can be created and managed with clearly defined collaboration between researchers and patient representatives across Europe. This paper provides guidance on the work required to set up PPIE structures within a large consortium to promote and support the creation of meaningful and efficient PPIE related to the development of digital mobility outcomes., (©Alison Keogh, Ríona Mc Ardle, Mara Gabriela Diaconu, Nadir Ammour, Valdo Arnera, Federica Balzani, Gavin Brittain, Ellen Buckley, Sara Buttery, Alma Cantu, Solange Corriol-Rohou, Laura Delgado-Ortiz, Jacques Duysens, Tom Forman-Hardy, Tova Gur-Arieh, Dominique Hamerlijnck, John Linnell, Letizia Leocani, Tom McQuillan, Isabel Neatrour, Ashley Polhemus, Werner Remmele, Isabel Saraiva, Kirsty Scott, Norman Sutton, Koen van den Brande, Beatrix Vereijken, Martin Wohlrab, Lynn Rochester, Mobilise-D consortium. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 27.10.2023.)

Background: The ticks Ixodes ricinus and Dermacentor reticulatus are two of the most important vectors in Europe. Climate niche modelling has been used in many studies to attempt to explain their distribution and to predict changes under a range of climate change scenarios. The aim of this study was to assess the ability of different climate niche modelling approaches to explain the known distribution of I. ricinus and D. reticulatus in Europe., Methods: A series of climate niche models, using different combinations of input data, were constructed and assessed. Species occurrence records obtained from systematic literature searches and Global Biodiversity Information Facility data were thinned to different degrees to remove sampling spatial bias. Four sources of climate data were used: bioclimatic variables, WorldClim, TerraClimate and MODIS satellite-derived data. Eight different model training extents were examined and three modelling frameworks were used: maximum entropy, generalised additive models and random forest models. The results were validated through internal cross-validation, comparison with an external independent dataset and expert opinion., Results: The performance metrics and predictive ability of the different modelling approaches varied significantly within and between each species. Different combinations were better able to define the distribution of each of the two species. However, no single approach was considered fully able to capture the known distribution of the species. When considering the mean of the performance metrics of internal and external validation, 24 models for I. ricinus and 11 models for D. reticulatus of the 96 constructed were considered adequate according to the following criteria: area under the receiver-operating characteristic curve > 0.7; true skill statistic > 0.4; Miller's calibration slope 0.25 above or below 1; Boyce index > 0.9; omission rate < 0.15., Conclusions: This comprehensive analysis suggests that there is no single 'best practice' climate modelling approach to account for the distribution of these tick species. This has important implications for attempts to predict climate-mediated impacts on future tick distribution. It is suggested here that climate variables alone are not sufficient; habitat type, host availability and anthropogenic impacts, not included in current modelling approaches, could contribute to determining tick presence or absence at the local or regional scale., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Here we report on Neanderthal engravings on a cave wall at La Roche-Cotard (LRC) in central France, made more than 57±3 thousand years ago. Following human occupation, the cave was completely sealed by cold-period sediments, which prevented access until its discovery in the 19th century and first excavation in the early 20th century. The timing of the closure of the cave is based on 50 optically stimulated luminescence ages derived from sediment collected inside and from around the cave. The anthropogenic origin of the spatially-structured, non-figurative marks found within the cave is confirmed using taphonomic, traceological and experimental evidence. Cave closure occurred significantly before the regional arrival of H. sapiens, and all artefacts from within the cave are typical Mousterian lithics; in Western Europe these are uniquely attributed to H. neanderthalensis. We conclude that the LRC engravings are unambiguous examples of Neanderthal abstract design., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Marquet et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Endoscopic retrograde cholangiopancreatography (ERCP) and EUS are challenging procedures requiring a high level of expertise to provide effective and safe patient care. Thus, high-quality training is needed to achieve competence. We aimed to evaluate the status of European ERCP/EUS training programs, to evaluate adherence to international recommendations, and to propose possible solutions for future improvements., Methods: A web-based survey was developed and ERCP/EUS experts and trainees across Europe were invited to participate., Results: Forty-one experts (out of 50; 82%) and 30 trainees (out of 70; 42.9%) from 18 countries answered the questionnaire. The training program application process is mainly driven by individual requests (87.8%). All surveyed departments offer combined ERCP/EUS training and the majority have adequate facilities and trainers. Although centers are high-volume and provide long-term fellowships, trainee hands-on exposure is not very high (43% expect to do (or did) 100-150 ERCPs and 69% up to 150 EUSs). A formal curriculum is in place in 53.7% centers, including simulation-training in 27.3%. Competence is assessed in 65.7% of centers, but validated tools are applied in only 33.3%., Conclusions: This survey first provides an overview of ERCP/EUS training programs across Europe. It shows that there is adherence to international guidelines to a certain degree, but several gaps in the application process, use of simulators for training, training curriculum and assessment of performance have been recognized. Overcoming these shortcomings could serve as a basis for further improvement in ERCP/EUS training., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Severe trauma represents a major global public health burden and the management of post-traumatic bleeding continues to challenge healthcare systems around the world. Post-traumatic bleeding and associated traumatic coagulopathy remain leading causes of potentially preventable multiorgan failure and death if not diagnosed and managed in an appropriate and timely manner. This sixth edition of the European guideline on the management of major bleeding and coagulopathy following traumatic injury aims to advise clinicians who care for the bleeding trauma patient during the initial diagnostic and therapeutic phases of patient management., Methods: The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma included representatives from six European professional societies and convened to assess and update the previous version of this guideline using a structured, evidence-based consensus approach. Structured literature searches covered the period since the last edition of the guideline, but considered evidence cited previously. The format of this edition has been adjusted to reflect the trend towards concise guideline documents that cite only the highest-quality studies and most relevant literature rather than attempting to provide a comprehensive literature review to accompany each recommendation., Results: This guideline comprises 39 clinical practice recommendations that follow an approximate temporal path for management of the bleeding trauma patient, with recommendations grouped behind key decision points. While approximately one-third of patients who have experienced severe trauma arrive in hospital in a coagulopathic state, a systematic diagnostic and therapeutic approach has been shown to reduce the number of preventable deaths attributable to traumatic injury., Conclusion: A multidisciplinary approach and adherence to evidence-based guidelines are pillars of best practice in the management of severely injured trauma patients. Further improvement in outcomes will be achieved by optimising and standardising trauma care in line with the available evidence across Europe and beyond., (© 2023. The Author(s).)

Objective: The aim of this study is to provide an update of the estimated proportion of avoidable cases across European region for cancers associated with modifiable risk factors., Methods: Age-standardised incidence rates for 38 European countries in 2020 were derived from GLOBOCAN database. For 17 cancer sites, we estimated the number and proportion of avoidable cancer cases. The mean of the three lowest country-specific incidence (excluding rates of zero) was defined as the attainable rate for each combination of cancer site, sex, and age group. The number and proportion of avoidable cancer cases was calculated as the difference between the country-specific and attainable incidence rates., Results: Approximately, 697,000 cancer cases (33%) of all cases in men, and 837,000 (44%) in women were potentially avoidable. Lung, colorectal, and female breast cancer contributed the largest avoidable burden from cancer, with a combined 790,000 cases, followed by mesothelioma, melanoma of the skin, laryngeal, and oesophageal cancer as major contributors. Large geographical variations were found in the estimated proportion of avoidable cancer cases by sex., Conclusions: A cohesive population-level preventative effort to reduce modifiable cancer risk factors could potentially have considerable impact in reducing the future burden of many cancers in Europe., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Specialty training in plastic, reconstructive and aesthetic surgery is a prerequisite for safe and effective provision of care. The aim of this study was to assess and portray similarities and differences in the continuing education and specialization in plastic surgery in Europe., Material and Methods: A detailed questionnaire was designed and distributed utilizing an online survey administration software. Questions addressed core items regarding continuing education and specialization in plastic surgery in Europe. Participants were addressed directly via the European Leadership Forum (ELF) of the European Society of Plastic, Reconstructive and Aesthetic Surgery (ESPRAS). All participants had detailed knowledge of the organization and management of plastic surgical training in their respective country., Results: The survey was completed by 29 participants from 23 European countries. During specialization, plastic surgeons in Europe are trained in advanced tissue transfer and repair and aesthetic principles in all parts of the human body and within several subspecialties. Moreover, rotations in intensive as well as emergency care are compulsory in most European countries. Board certification is only provided for surgeons who have had multiple years of training regulated by a national board, who provide evidence of individually performed operative procedures in several anatomical regions and subspecialties, and who pass a final oral and/or written examination., Conclusion: Board certified plastic surgeons meet the highest degree of qualification, are trained in all parts of the body and in the management of complications. The standard of continuing education and qualification of European plastic surgeons is high, providing an excellent level of plastic surgical care throughout Europe., Hintergrund: Die Facharzt-Weiterbildung für Plastische und Ästhetische Chirurgie ist eine Grundvoraussetzung für sichere und effektive Patientenversorgung. Ziel der vorliegenden Studie war die Darstellung von Gemeinsamkeiten und Unterschieden in der Weiterbildung für Plastische Chirurgie innerhalb von Europa., Materialien Und Methoden: Ein internetbasierter Fragebogen wurde mit Hilfe eines kostenlosen Formularerstellungstools erstellt und verteilt. Die Fragen betrafen Kernpunkte der Weiterbildung für Plastische Chirurgie in Europa. Die Teilnehmer wurden direkt über das European Leadership Forum (ELF) der European Society of Plastic, Reconstructive and Aesthetic Surgery (ESPRAS) kontaktiert. Alle Teilnehmer hatten weitreichende Kenntnisse über die Organisation und Struktur der plastisch-chirurgischen Weiterbildung in ihrem jeweiligen Land., Ergebnisse: 29 Teilnehmer*innen aus 23 europäischen Ländern nahmen an der Umfrage teil. Die Weiterbildung für Plastische Chirurgie beinhaltet grundlegende Prinzipien und Techniken zur Wiederherstellung von Form und Funktion innerhalb der verschiedenen Säulen der Plastischen Chirurgie, sowie in allen Körperregionen. In den meisten europäischen Ländern ist eine Rotation in der Intensiv- und Notfallmedizin und die Behandlung kritisch kranker Patienten obligatorisch. Voraussetzung für die Facharztbezeichnung ist die mehrjährige, national organisierte Weiterbildung, der Nachweis einer festgelegten Anzahl selbstständig durchgeführter Operationen, sowie die mündliche und/oder schriftliche Abschlussprüfung., Schlussfolgerung: Fachärzte für Plastische und Ästhetische Chirurgie sind hochqualifiziert und auch im Umgang mit Komplikationen geschult. Der Standard der Weiterbildung der europäischen Plastischen Chirurgen ist hoch, so dass innerhalb Europas eine hohe Qualität plastisch-chirurgischer Versorgung gewährleistet ist., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

The COVID-19 pandemic has highlighted the need to modernize healthcare systems to the reality of the 21st century. The first world-wide Strategic Committee to launch Collaborative Value-Based Healthcare (C-VBHC) anchored on populational Real World Data and structured collaboration, took place in Montreal, via TOWWERS showcase project. The meeting covered a broad range of topics from the perspective of each of the various Real-World healthcare actors, the 5P+: Patient, Prescriber, Producer, Policymaker, Payer, including Data and Research stakeholders. Attended by approximately 20 participants from North America and Europe, the meeting provided a valuable opportunity to unit the 5P+ around common goals and exchanging on solutions. TOWWERS Strategic committee identified key elements required to continue the transformation.

Background: Species from the Trichophyton benhamiae complex are mostly zoophilic dermatophytes which cause inflammatory dermatophytosis in animals and humans worldwide., Objectives: This study was purposed to (a) to identify 169 reference and clinical dermatophyte strains from the T benhamiae complex species by molecular method and adhering to the newest taxonomy in the complex (b) to evaluate the in vitro antifungal susceptibility profile of these strains against eight common and new antifungal agents that may be used for the treatment of dermatophytosis., Methods: All isolates, mainly originated from Europe but also from Iran, Japan and USA, were subjected to ITS-rDNA sequencing. The in vitro antifungal susceptibility profiles of eight common and new antifungal drugs against the isolates were determined by CLSI M38-A2 protocol and according to microdilution method., Results: Based on the ITS-rDNA sequencing, T benhamiae was the dominant species (n = 102), followed by T europaeum (n = 29), T erinacei (n = 23), T japonicum (n = 10), Trichophyton sp (n = 4) and T eriotrephon (n = 1). MIC ranges across all isolates were as follows: luliconazole: 0.0002-0.002 µg/ml, terbinafine: 0.008-0.125 µg/ml, efinaconazole: 0.008-0.125 µg/ml, ciclopirox olamine: 0.03-0.5 µg/ml, itraconazole: 0.06-2 µg/ml, griseofulvin: 0.25-4 µg/ml, amorolfine hydrochloride: 0.125-4 µg/ml and tavaborole: 1-16 µg/ml., Conclusion: Luliconazole, efinaconazole and terbinafine were the most potent antifungals against T benhamiae complex isolates, regardless of the geographic locations where strains were isolated. These data might help dermatologists to develop effective therapies for successful treatment of infections due to T benhamiae complex species., (© 2021 Wiley-VCH GmbH.)

Introduction: Europe is an important focus for compiling accurate and up-to-date world cancer statistics owing to its large share of the world's total cancer burden. This article presents incidence and mortality estimates for 25 major cancers across 40 individual countries within European areas and the European Union (EU-27) for the year 2020., Methods: The estimated national incidence and mortality rates are based on statistical methodology previously applied and verified using the most recently collected incidence data from 151 population-based cancer registries, mortality data and 2020 population estimates., Results: Estimates reveal 4 million new cases of cancer (excluding non-melanoma skin cancer) and 1.9 million cancer-related deaths. The most common cancers are: breast in women (530,000 cases), colorectum (520,000), lung (480,000) and prostate (470,000). These four cancers account for half the overall cancer burden in Europe. The most common causes of cancer deaths are: lung (380,000), colorectal (250,000), breast (140,000) and pancreatic (130,000) cancers. In EU-27, the estimated new cancer cases are approximately 1.4 million in males and 1.2 million in females, with over 710,000 estimated cancer deaths in males and 560,000 in females., Conclusion: The 2020 estimates provide a basis for establishing priorities in cancer-control measures across Europe. The long-established role of cancer registries in cancer surveillance and the evaluation of cancer control measures remain fundamental in formulating and adapting national cancer plans and pan-European health policies. Given the estimates are built on recorded data prior to the onset of coronavirus disease 2019 (COVID-19), they do not take into account the impact of the pandemic., Competing Interests: Conflict of interest statement None declared., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: This post-authorisation safety study estimated the risk of anaphylaxis in patients receiving intravenous (IV) iron in Europe, with interest in iron dextran and iron non-dextrans. Studies conducted in the United States have reported risk of anaphylaxis to IV iron ranging from 2.0 to 6.8 per 10 000 first treatments., Methods: Cohort study of IV iron new users, captured mostly through pharmacy ambulatory dispensing, from populations covered by health and administrative data sources in five European countries from 1999 to 2017. Anaphylaxis events were identified through an algorithm that used parenteral penicillin as a positive control., Results: A total of 304 210 patients with a first IV iron treatment (6367 iron dextran), among whom 13-16 anaphylaxis cases were identified and reported as a range to comply with data protection regulations. The pooled unadjusted incidence proportion (IP) ranged from 0.4 (95% confidence interval [CI], 0.2-0.9) to 0.5 (95% CI, 0.3-1.0) per 10 000 first treatments. No events were identified at first dextran treatments. There were 231 294 first penicillin treatments with 30 potential cases of anaphylaxis (IP = 1.2; 95% CI, 0.8-1.7 per 10 000 treatments)., Conclusion: We found an IP of anaphylaxis from 0.4 to 0.5 per 10 000 first IV iron treatments. The study captured only a fraction of IV iron treatments administered in hospitals, where most first treatments are likely to happen. Due to this limitation, the study could not exclude a differential risk of anaphylaxis between iron dextran and iron non-dextrans. The IP of anaphylaxis in users of penicillin was consistent with incidences reported in the literature., (© 2021 Vifor (International) AG. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Purpose: Although NRG1 fusions are oncogenic drivers across multiple tumor types including lung cancers, these are difficult to study because of their rarity. The global eNRGy1 registry was thus established to characterize NRG1 fusion-positive lung cancers in the largest and most diverse series to date., Methods: From June 2018 to February 2020, a consortium of 22 centers from nine countries in Europe, Asia, and the United States contributed data from patients with pathologically confirmed NRG1 fusion-positive lung cancers. Profiling included DNA-based and/or RNA-based next-generation sequencing and fluorescence in situ hybridization. Anonymized clinical, pathologic, molecular, and response (RECIST v1.1) data were centrally curated and analyzed., Results: Although the typified never smoking (57%), mucinous adenocarcinoma (57%), and nonmetastatic (71%) phenotype predominated in 110 patients with NRG1 fusion-positive lung cancer, further diversity, including in smoking history (43%) and histology (43% nonmucinous and 6% nonadenocarcinoma), was elucidated. RNA-based testing identified most fusions (74%). Molecularly, six (of 18) novel 5' partners, 20 unique epidermal growth factor domain-inclusive chimeric events, and heterogeneous 5'/3' breakpoints were found. Platinum-doublet and taxane-based (post-platinum-doublet) chemotherapy achieved low objective response rates (ORRs 13% and 14%, respectively) and modest progression-free survival medians (PFS 5.8 and 4.0 months, respectively). Consistent with a low programmed death ligand-1 expressing (28%) and low tumor mutational burden (median: 0.9 mutations/megabase) immunophenotype, the activity of chemoimmunotherapy and single-agent immunotherapy was poor (ORR 0%/PFS 3.3 months and ORR 20%/PFS 3.6 months, respectively). Afatinib achieved an ORR of 25%, not contingent on fusion type, and a 2.8-month median PFS., Conclusion: NRG1 fusion-positive lung cancers were molecularly, pathologically, and clinically more heterogeneous than previously recognized. The activity of cytotoxic, immune, and targeted therapies was disappointing. Further research examining NRG1 -rearranged tumor biology is needed to develop new therapeutic strategies., Competing Interests: Alexander DrilonHonoraria: Medscape, OncLive, PeerVoice, Physicans' Education Resource, Targeted Oncology, MORE Health, Research to Practice, Foundation Medicine, PeerviewConsulting or Advisory Role: Ignyta, Loxo, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Genentech/Roche, Helsinn Therapeutics, BeiGene, Hengrui Therapeutics, Exelixis, Bayer, Tyra Biosciences, Verastem, Takeda/Millennium, BerGenBio, MORE Health, Lilly, Verastem, AbbVie, 14ner Oncology/Elevation Oncology, Remedica, Archer, Monopteros Therapeutics, Novartis, EMD Serono/Merck, Melendi, Repare TherapeuticsResearch Funding: Foundation MedicinePatents, Royalties, Other Intellectual Property: Wolters Kluwer (royalties for Pocket Oncology)Other Relationship: Merck, GlaxoSmithKline, Teva, Taiho Pharmaceutical, Pfizer, PharmaMar, Puma Biotechnology Michael DuruisseauxConsulting or Advisory Role: AstraZeneca, MSD Oncology, BMS, Pfizer, Roche, Takeda, Boehringer Ingelheim, Janssen Oncology, Amgen, AbbVieTravel, Accommodations, Expenses: Boehringer Ingelheim, Merck Sharp & Dohme Ji-Youn HanHonoraria: Roche, AstraZeneca, Bristol Myers Squibb, TakedaConsulting or Advisory Role: MSD Oncology, AstraZeneca, Bristol Myers Squibb, Lilly, Novartis, Takeda, PfizerResearch Funding: Roche, Pfizer, Ono Pharmaceutical, Takeda Soo-Ryum YangConsulting or Advisory Role: Invitae Yonina R. Murciano-GoroffTravel, Accommodations, Expenses: AstraZeneca Morihito OkadaSpeakers' Bureau: Taiho Pharmaceutical, Johnson & Johnson, Covidien, Lilly, Chugai Pharma, AstraZeneca, Ono Pharmaceutical, CSL BehringResearch Funding: Taiho Pharmaceutical, Nippon Kayaku, Chugai Pharma, Covidien, Johnson & Johnson, Daiichi Sankyo, Yakult Honsha, Lilly Japan, Nihon Medi-Physics, Pfizer, Mochida Pharmaceutical Co Ltd, Shionogi, Ono Pharmaceutical, Kyowa Hakko Kirin Miguel Angel MolinaEmployment: Pangaea OncologyResearch Funding: AstraZeneca, Merck Serono, In3Bio Marie WislezConsulting or Advisory Role: Boehringer Ingelheim, Roche, MSD Oncology, Bristol Myers Squibb, AstraZeneca, AmgenSpeakers' Bureau: Boehringer Ingelheim, Amgen, Roche, MSD Oncology, Bristol Myers Squibb, AstraZenecaTravel, Accommodations, Expenses: Roche, MSD Oncology Alexa SchrockEmployment: Foundation MedicineStock and Other Ownership Interests: Foundation Medicine, Roche Siraj AliEmployment: EQRX (I), Foundation Medicine, EQRXLeadership: Incysus Inc, Elevation Oncology, Pillar BiosciencesStock and Other Ownership Interests: Exelixis, Merus NV, PfizerConsulting or Advisory Role: Azitra (I), Princepx Tx (I)Patents, Royalties, and Other Intellectual Property:Patents via Seres Health on microbiome in non neoplastic disease (I), Foundation Medicine Valérie GounantConsulting or Advisory Role: Bristol Myers Squibb, Takeda, Roche, AstraZeneca, Boehringer Ingelheim, Novartis, Chugai Pharma EuropeTravel, Accommodations, Expenses: Takeda, Roche, Pfizer Alison M. SchramResearch Funding: Merus, Kura Oncology, Surface Oncology, AstraZeneca, Lilly, Northern Biologics, Pfizer, Black Diamond Therapeutics, BeiGene, Relay Therapeutics Isabelle MonnetTravel, Accommodations, Expenses: MSD Oncology, Roche, Takeda, Pfizer Jin-Yuan ShihHonoraria: AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, Merck Sharp & Dohme, Ono Pharmaceutical, Bristol Myers Squibb, Roche, Chugai Pharma, LillyConsulting or Advisory Role: Chugai Pharma, Boehringer Ingelheim, Bristol Myers Squibb, Roche, AstraZeneca, Lilly, Takeda, CStone Pharmaceuticals, Janssen Oncology, Novartis, Pfizer, Ono Pharmaceutical, Merck Sharp & DohmeResearch Funding: RocheTravel, Accommodations, Expenses: Bristol Myers Squibb, Pfizer, Chugai Pharma, Roche Joshua SabariConsulting or Advisory Role: AstraZeneca, Janssen Oncology, Navire, Pfizer, Regeneron, Medscape, Takeda Maurice PérolConsulting or Advisory Role: Lilly, Roche/Genentech, Pfizer, AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, Bristol Myers Squibb, Novartis, Amgen, Takeda, Chugai Pharma, Gritstone OncologyResearch Funding: AstraZeneca, Roche, Takeda, Boehringer IngelheimTravel, Accommodations, Expenses: AstraZeneca, Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Pfizer, Takeda, Chugai Pharma Viola W. ZhuStock and Other Ownership Interests: TP TherapeuticsHonoraria: AstraZeneca, Roche/Genentech, Takeda, Blueprint Medicines, XcoveryConsulting or Advisory Role: AstraZeneca, Takeda, TP Therapeutics, Roche/Genentech, XcoverySpeakers' Bureau: AstraZeneca, Roche/Genentech, Takeda, Blueprint MedicinesTravel, Accommodations, Expenses: AstraZeneca, Roche/Genentech, Takeda, TP Therapeutics Misako NagasakaConsulting or Advisory Role: AstraZeneca, Caris Life Sciences, Daiichi Sankyo, Takeda, Novartis, EMD SeronoSpeakers' Bureau: Blueprint MedicinesResearch Funding: TempusTravel, Accommodations, Expenses: Anheart Therapeutics Robert DoebeleEmployment: Rain TherapeuticsLeadership: Rain TherapeuticsStock and Other Ownership: Rain TherapeuticsConsulting or Advisory Role: GreenPeptide, AstraZeneca, Roche/Genentech, Bayer, Takeda, Rain Therapeutics, Anchiano, Blueprint Medicines, Foundation Medicine, Guardant HealthPatents, Royalties, and Other Intellectual Property: Abbott Molecular for Patent PCT/US2013/057495, Rain Therapeutics, Genentech (Inst), Foundation Medicine (Inst), Black Diamond (Inst), Pearl River (Inst), Voronoi (Inst)Travel, Accommodations, Expenses: Rain Therapeutics, Roche/Genentech D. Ross CamidgeHonoraria: Roche, Takeda, AstraZeneca, Daiichi Sankyo, Bio-Thera, Ribon Therapeutics, Bristol Myers Squibb, Inivata, AbbVie, Apollomics, Elevation Oncology, EMD Serono, Helsinn Therapeutics, Lilly, Nuvalent Inc, Seattle Genetics, Turning Point Therapeutics, Kestrel Labs, Amgen Astellas BioPharma, Anchiano, Eisai, GlaxoSmithKline, Janssen, OnKure, Mersana, Pfizer, QiLu Pharmaceutical, SanofiResearch Funding: Takeda Maria ArcilaHonoraria: Invivoscribe, BiocartisConsulting or Advisory Role: AstraZenecaTravel, Accommodations, Expenses: AstraZeneca, Invivoscribe, Raindance Technologies Sai-Hong Ignatius OuStock and Other Ownership Interests: Turning Point Therapeutics, Elevation OncologyHonoraria: Pfizer, Roche Pharma AG, Genentech/Roche, ARIAD/Takeda, AstraZenecaConsulting or Advisory Role: Pfizer, Roche/Genentech, AstraZeneca, Takeda, Jassen/JNJSpeakers' Bureau: AstraZeneca, Genentech/RocheResearch Funding: Pfizer, Roche Pharma AG, AstraZeneca/MedImmune, AstraZeneca, ARIAD, Revolution Medicines, Mirati Therapeutics, Jassen/JNJ Denis Moro-SibilotConsulting or Advisory Role: Roche/Genentech, Boehringer Ingelheim, Lilly/ImClone, Sanofi, Novartis, Amgen, Pfizer, AstraZeneca, Clovis Oncology, MSD Oncology, ARIAD, Bristol-Myers Squibb, Takeda, AbbvieResearch Funding: Abbvie (Inst), Boehr (Inst), Roche/Genentech (Inst), Bristol-Myers Squibb (Inst)Expert Testimony: MSD OncologyTravel, Accommodations, Expenses: Roche/Genentech, Lilly/ImClone, Pfizer, MSD Oncology, Bristol-Myers Squibb Lucia Anna MuscarellaTravel, Accommodations, Expenses: Boehringer Ingelheim Stephen V. LiuConsulting or Advisory Role: Genentech, Pfizer, Lilly, Bristol Myers Squibb, AstraZeneca, Takeda, Regeneron, G1 Therapeutics, Guardant Health, Janssen Oncology, MSD Oncology, Jazz Pharmaceuticals, Blueprint Medicines, Inivata, PharmaMar, Daiichi Sankyo/UCB Japan, BeiGene, AmgenResearch Funding: Genentech/Roche, Pfizer, Corvus Pharmaceuticals, Bayer, Merck, Lycera, AstraZeneca, Molecular Partners, Blueprint Medicines, Lilly, Rain Therapeutics, Alkermes, Bristol Myers Squibb, Turning Point Therapeutics, RAPT Therapeutics, Merus, Debiopharm Group, Elevation OncologyTravel, Accommodations, Expenses: AstraZeneca, Roche/Genentech, MSD Oncology Jacques CadranelHonoraria: AstraZeneca/MedImmune, Bristol Myers Squibb, Roche/Genentech, Merck Sharp & Dohme, Boehringer IngelheimConsulting or Advisory Role: AstraZeneca/MedImmune, Roche/Genentech, Boehringer Ingelheim, Bristol Myers Squibb, Takeda, Merck Sharp & Dohme, Pfizer, Lilly, NovartisResearch Funding: Pfizer, Novartis, AstraZeneca/MedImmuneNo other potential conflicts of interest were reported.

Reproductive longevity is essential for fertility and influences healthy ageing in women 1,2 , but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations 3 . The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Ovarian cancer risk in BRCA1 and BRCA2 mutation carriers has been shown to decrease with longer duration of oral contraceptive use. Although the effects of using oral contraceptives in the general population are well established (approximately 50% risk reduction in ovarian cancer), the estimated risk reduction in mutation carriers is much less precise because of potential bias and small sample sizes. In addition, only a few studies on oral contraceptive use have examined the associations of duration of use, time since last use, starting age, and calendar year of start with risk of ovarian cancer., Objective: This study aimed to investigate in more detail the associations of various characteristics of oral contraceptive use and risk of ovarian cancer, to provide healthcare providers and carriers with better risk estimates., Study Design: In this international retrospective study, ovarian cancer risk associations were assessed using oral contraceptives data on 3989 BRCA1 and 2445 BRCA2 mutation carriers. Age-dependent-weighted Cox regression analyses were stratified by study and birth cohort and included breast cancer diagnosis as a covariate. To minimize survival bias, analyses were left truncated at 5 years before baseline questionnaire. Separate analyses were conducted for each aspect of oral contraceptive use and in a multivariate analysis, including all these aspects. In addition, the analysis of duration of oral contraceptive use was stratified by recency of use., Results: Oral contraceptives were less often used by mutation carriers who were diagnosed with ovarian cancer (ever use: 58.6% for BRCA1 and 53.5% BRCA2) than by unaffected carriers (ever use: 88.9% for BRCA1 and 80.7% for BRCA2). The median duration of use was 7 years for both BRCA1 and BRCA2 carriers who developed ovarian cancer and 9 and 8 years for unaffected BRCA1 and BRCA2 carriers with ovarian cancer, respectively. For BRCA1 mutation carriers, univariate analyses have shown that both a longer duration of oral contraceptive use and more recent oral contraceptive use were associated with a reduction in the risk of ovarian cancer. However, in multivariate analyses, including duration of use, age at first use, and time since last use, duration of oral contraceptive use proved to be the prominent protective factor (compared with <5 years: 5-9 years [hazard ratio, 0.67; 95% confidence interval, 0.40-1.12]; >10 years [hazard ratio, 0.37; 95% confidence interval, 0.19-0.73]; P trend =.008). The inverse association between duration of use and ovarian cancer risk persisted for more than 15 years (duration of ≥10 years; BRCA1 <15 years since last use [hazard ratio, 0.24; 95% confidence interval, 0.14-0.43]; BRCA1 >15 years since last use [hazard ratio, 0.56; 95% confidence interval, 0.18-0.59]). Univariate results for BRCA2 mutation carriers were similar but were inconclusive because of limited sample size., Conclusion: For BRCA1 mutation carriers, longer duration of oral contraceptive use is associated with a greater reduction in ovarian cancer risk, and the protection is long term., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: The United Network for Organ Sharing's Model for End-Stage Liver Disease (UNOS-MELD) score is the basis of liver allocation in the Eurotransplant region. It was constructed 20 years ago in a small US cohort and has remained unchanged ever since. The best boundaries and coefficients were never calculated for any region outside the United States. Therefore, this study refits the MELD (reMELD) for the Eurotransplant region., Approach and Results: All adult patients listed for a first liver transplantation between January 1, 2007, and December 31, 2018, were included. Data were randomly split in a training set (70%) and a validation set (30%). In the training data, generalized additive models with splines were plotted for each MELD parameter. The lower and upper bound combinations with the maximum log-likelihood were chosen for the final models. The refit models were tested in the validation data with C-indices and Brier scores. Through likelihood ratio tests the refit models were compared to UNOS-MELD. The correlation between scores and survival of prioritized patients was calculated. A total of 6,684 patients were included. Based on training data, refit parameters were capped at creatinine 0.7-2.5, bilirubin 0.3-27, international normalized ratio 0.1-2.6, and sodium 120-139. ReMELD and reMELD-Na showed C-indices of 0.866 and 0.869, respectively. ReMELD-Na prioritized patients with 1.6 times higher 90-day mortality probabilities compared to UNOS-MELD., Conclusions: Refitting MELD resulted in new lower and upper bounds for each parameter. The predictive power of reMELD-Na was significantly higher than UNOS-MELD. ReMELD prioritized patients with higher 90-day mortality rates. Thus, reMELD(-Na) should replace UNOS-MELD for liver graft allocation in the Eurotransplant region., (© 2020 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Objectives: The objective of this study was to investigate the feasibility of defining diagnostic reference levels (DRLs) on a European basis for specific clinical indications (CIs), within the context of the European Clinical DRLs (EUCLID) European Commission project., Methods: A prospective, multicenter, industry-independent European study was performed to provide data on 10 CIs (stroke, chronic sinusitis, cervical spine trauma, pulmonary embolism, coronary calcium scoring, coronary angiography, lung cancer, hepatocellular carcinoma, colic/abdominal pain, and appendicitis) via an online survey that included information on patient clinical, technical, and dosimetric parameters. Data from at least 20 patients per CI were requested from each hospital. To establish DRLs, a methodology in line with the International Commission on Radiological Protection (ICRP) Report 135 good practice recommendations was followed., Results: Data were collected from 19 hospitals in 14 European countries on 4299 adult patients and 10 CIs to determine DRLs. DRLs differ considerably between sites for the same CI. Differences were attributed mainly to technical protocol and variable number of phases/scan lengths. Stroke and hepatocellular carcinoma were the CIs with the highest DRLs. Coronary calcium scoring had the lowest DRL value. Comparison with published literature was limited, as there was scarce information on DRLs based on CI., Conclusions: This is the first study reporting on feasibility of establishing CT DRLs based on CI using European data. Resulting values will serve as a baseline for comparison with local radiological practice, national authorities when DRLs are set/updated, or as a guideline for local DRL establishment., Key Points: • First study reporting on the feasibility of establishing CT diagnostic reference levels based on clinical indication using data collected across Europe. • Only one-fourth of the hospitals had CT machines less than 5 years old. • Large dose variations were observed among hospitals and CT protocols were quite different between hospitals.

Objective: This multilanguage study used simple speech recording and high-end pattern analysis to provide sensitive and reliable noninvasive biomarkers of prodromal versus manifest α-synucleinopathy in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) and early-stage Parkinson disease (PD)., Methods: We performed a multicenter study across the Czech, English, German, French, and Italian languages at 7 centers in Europe and North America. A total of 448 participants (337 males), including 150 with iRBD (mean duration of iRBD across language groups 0.5-3.4 years), 149 with PD (mean duration of disease across language groups 1.7-2.5 years), and 149 healthy controls were recorded; 350 of the participants completed the 12-month follow-up. We developed a fully automated acoustic quantitative assessment approach for the 7 distinctive patterns of hypokinetic dysarthria., Results: No differences in language that impacted clinical parkinsonian phenotypes were found. Compared with the controls, we found significant abnormalities of an overall acoustic speech severity measure via composite dysarthria index for both iRBD (p = 0.002) and PD (p < 0.001). However, only PD (p < 0.001) was perceptually distinct in a blinded subjective analysis. We found significant group differences between PD and controls for monopitch (p < 0.001), prolonged pauses (p < 0.001), and imprecise consonants (p = 0.03); only monopitch was able to differentiate iRBD patients from controls (p = 0.004). At the 12-month follow-up, a slight progression of overall acoustic speech impairment was noted for the iRBD (p = 0.04) and PD (p = 0.03) groups., Interpretation: Automated speech analysis might provide a useful additional biomarker of parkinsonism for the assessment of disease progression and therapeutic interventions. ANN NEUROL 2021;90:62-75., (© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Purpose: During the Middle Ages, the Christian church established itself as the dominant force over all aspects of medieval life, including the practice of medicine. As the Church's influence expanded across Europe, the role of lay practitioners in medicine declined, and clerics gradually assumed the role of healers in surgical practice as the cure of the soul was felt to take precedence over cure of bodily ills., Material and Methods: A retrospective analysis of hospital foundation, old-school surgical techniques still used today was performed during the first part of the Middle Age., Results: The Hospital Hotel Dieu in Paris was founded and remains the oldest worldwide still-operating hospital. The monastery became a resting place for travelers, as well as a place of refuge for the sick. As this role expanded, monks often developed considerable surgical expertise. This led to fierce competition for saintly relics and pilgrims. Among the myriad of saints to whom powers of healing were ascribed, the names of Damian and Cosmas figure prominently in medical history. Old-school medieval surgery was also performed with some bizarre techniques such as lip service by wound suckers, cautery, blood-letting, leech therapy, and maggot therapy., Conclusion: This account of surgery before it became scientific is based on a chronology that runs from the Clovis baptism to the reign of Charlemagne; much of the medicine in this period was based on ancient doctrines; indeed, much of the development of medicine in the period called as "Dark Age" was due to the slow and difficult business of recovering and trying to understand ancient medicine.

The feasibility of freezing and thawing ovarian tissue is nowadays widely documented. However, ovarian tissue transplantation (OTT) is happening at a much slower pace, and clinical experience is somewhat limited. In this review, five European centers present their collective experience of transplanting ovarian tissue in 285 women. The focus is on surgical techniques and OTT outcomes, reproductive outcomes, the impact of chemotherapy before ovarian tissue cryopreservation (OTC), the risk of relapse, and endocrine resumption and longevity of transplanted tissue. The risk of relapse due to reimplantation of ovarian tissue appears to be very low according to current data. Recovery of endocrine function is seen in almost all women undergoing transplantation of ovarian tissue, and about one in four gives birth to a healthy child. The efficacy of in vitro fertilization in these patients is not very high, however, and needs to be substantially improved. Radiation to the pelvis, especially with relatively high doses, appears to considerably decrease the likelihood of a successful pregnancy and may be contraindicated. Our results demonstrate that chemotherapy before OTC does not impair the chances of success, depending, of course, on the total dose and type of chemotherapy administered. At this early stage of development of OTT for restoration of fertility, the results are encouraging and demonstrate clear potential. However, the method is far from being fully developed and requires continued research efforts to optimize our approach., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control., (© 2021 American Cancer Society.)

IntroductionIn contrast to countries where carbapenemase-producing Enterobacterales (CPE) are endemic, only sporadic cases were reported in Switzerland until 2013. An aggravation of the epidemiological situation in neighbouring European countries indicated the need for a surveillance study in Switzerland.AimWe aimed to describe CPE distributions in Switzerland and identify epidemiological factors associated with changes in incidence.MethodsData on all human CPE isolates from 2013 to 2018 were collected by the Swiss Centre for Antibiotic Resistance (ANRESIS) and analysed for temporal and regional trends by Generalised Poisson regression. Isolates associated with infection or colonisation were included in a primary analysis; a secondary analysis included invasive isolates only. Statistical detection of regional clusters was performed with WHONET/SaTScan.ResultsWe analysed 731 CPE isolates, of which 325 (44.5%) were associated with screenings and 173 (23.7%) with infections. Yearly detection of CPE isolates increased considerably during the study period from 65 to 212. The most frequently isolated species were Klebsiella pneumoniae (54%) and Escherichia coli (28%). The most frequent genotypes were OXA-48 (43%), KPC (21%) and NDM (14%). In contrast to the French-speaking parts of Switzerland (West, Geneva) where OXA-48 were the predominant genotypes (around 60%), KPC was the most frequently detected genotype in the Italian-speaking region (63%). WHONET/SaTScan outbreak detection analysis identified seven clusters in five regions of Switzerland.ConclusionsIn a first continuous surveillance of CPE in Switzerland, we found that the epidemiological situation aggravated nationwide and that regional patterns of CPE genotypes mirrored the situation in neighbouring European countries.

Improving vaccination of the elderly is one of the most important challenges in the coming years, as it was for infant's decades ago. Insufficient vaccine uptake in the elderly can be considered a concern with regard to the burden of vaccine preventable diseases in this growing population. The purpose of this paper is to have an overview on the different steps involved in decision policy making from the regulatory agencies until people are vaccinated. Examples of different policies within European countries will be compared for influenza, streptococcal and zoster infections. For each step, key improvements to increase vaccine uptake in this specific population will be proposed.

Introduction: Common Variable Immunodeficiency (CVID) is characterized by defective antibody production and hypogammaglobulinemia. Flow cytometry immunophenotyping of blood lymphocytes has become of great relevance for the diagnosis and classification of CVID, due to an impaired differentiation of mature post-germinal-center (GC) class-switched memory B-cells (MBC) and severely decreased plasmablast/plasma cell (Pb) counts. Here, we investigated in detail the pre-GC B-cell maturation compartment in blood of CVID patients., Methods: In this collaborative multicentric study the EuroFlow PID 8-color Pre-GC B-cell tube , standardized sample preparation procedures (SOPs) and innovative data analysis tools, were used to characterize the maturation profile of pre-GC B-cells in 100 CVID patients, vs 62 age-matched healthy donors (HD)., Results: The Pre-GC B-cell tube allowed identification within pre-GC B-cells of three subsets of maturation associated immature B-cells and three subpopulations of mature naïve B-lymphocytes. CVID patients showed overall reduced median absolute counts (vs HD) of the two more advanced stages of maturation of both CD5 + CD38 +/++ CD21 het CD24 ++ (2.7 vs 5.6 cells/µl, p=0.0004) and CD5 + CD38 het CD21 + CD24 + (6.5 vs 17 cells/µl, p<0.0001) immature B cells (below normal HD levels in 22% and 37% of CVID patients). This was associated with an expansion of CD21 - CD24 - (6.1 vs 0.74 cells/µl, p<0.0001) and CD21 - CD24 ++ (1.8 vs 0.4 cells/µl, p<0.0001) naïve B-cell counts above normal values in 73% and 94% cases, respectively. Additionally, reduced IgMD + (21 vs 32 cells/µl, p=0.03) and IgMD - (4 vs 35 cells/µl, p<0.0001) MBC counts were found to be below normal values in 25% and 77% of CVID patients, respectively, always together with severely reduced/undetectable circulating blood pb. Comparison of the maturation pathway profile of pre-GC B cells in blood of CVID patients vs HD using EuroFlow software tools showed systematically altered patterns in CVID. These consisted of: i) a normally-appearing maturation pathway with altered levels of expression of >1 (CD38, CD5, CD19, CD21, CD24, and/or smIgM) phenotypic marker (57/88 patients; 65%) for a total of 3 distinct CVID patient profiles (group 1: 42/88 patients, 48%; group 2: 8/88, 9%; and group 3: 7/88, 8%) and ii) CVID patients with a clearly altered pre-GC B cell maturation pathway in blood (group 4: 31/88 cases, 35%)., Conclusion: Our results show that maturation of pre-GC B-cells in blood of CVID is systematically altered with up to four distinctly altered maturation profiles. Further studies, are necessary to better understand the impact of such alterations on the post-GC defects and the clinical heterogeneity of CVID., Competing Interests: JD, MB, TK, MP-A, EL-G, A-KK, EB, and AO each report being one of the inventors on the EuroFlow-owned patent PCT/NL 2015/050762 (Diagnosis of primary immunodeficiencies), which is licensed to Cytognos, a company that pays royalties to the EuroFlow Consortium., (Copyright © 2021 del Pino-Molina, López-Granados, Lecrevisse, Torres Canizales, Pérez-Andrés, Blanco, Wentink, Bonroy, Nechvatalova, Milota, Kienzler, Philippé, Sousa, van der Burg, Kalina, van Dongen and Orfao.)

Background: Few studies have considered aircraft noise annoyance and noise sensitivity in analyses of the health effects of aircraft noise, especially in relation to medication use. This study aims to investigate the moderating and mediating role of these two factors in the relationship between aircraft noise levels and medication use among 5860 residents of ten European airports included in the HYENA and DEBATS studies., Methods: Information on aircraft noise annoyance, noise sensitivity, medication use, and demographic, socio-economic and lifestyle factors was collected during a face-to-face interview at home. Medication was coded according to the Anatomical Therapeutic Chemical (ATC) classification. Outdoor aircraft noise exposure was estimated by linking the participant's home address to noise contours using Geographical Information Systems (GIS) methods. Logistic regressions with adjustment for potential confounding factors were used. In addition, Baron and Kenny's recommendations were followed to investigate the moderating and mediating effects of aircraft noise annoyance and noise sensitivity., Results: A significant association was found between aircraft noise levels at night and antihypertensive medication only in the UK (OR = 1.43, 95%CI 1.19-1.73 for a 10 dB(A)-increase in L night ). No association was found with other medications. Aircraft noise annoyance was significantly associated with the use of antihypertensive medication (OR = 1.33, 95%CI 1.14-1.56), anxiolytics (OR = 1.48, 95%CI 1.08-2.05), hypnotics and sedatives (OR = 1.60, 95%CI 1.07-2.39), and antasthmatics (OR = 1.44, 95%CI 1.07-1.96), with no difference between countries. Noise sensitivity was significantly associated with almost all medications, with the exception of the use of antasthmatics, showing an increase in ORs with the level of noise sensitivity, with differences in ORs among countries only for the use of antihypertensive medication. The results also suggested a mediating role of aircraft noise annoyance and a modifying role of both aircraft noise annoyance and noise sensitivity in the association between aircraft noise levels and medication use., Conclusions: The present study is consistent with the results of the small number of studies available to date suggesting that both aircraft noise annoyance and noise sensitivity should be taken into account in analyses of the health effects of exposure to aircraft noise.

Objectives: Mild cognitive impairment (MCI) is associated with an increased risk of further cognitive decline, partly depending on demographics and biomarker status. The aim of the present study was to survey the clinical practices of physicians in terms of biomarker counseling, management, and follow-up in European expert centers diagnosing patients with MCI., Methods: An online email survey was distributed to physicians affiliated with European Alzheimer's disease Consortium centers (Northern Europe: 10 centers; Eastern and Central Europe: 9 centers; and Southern Europe: 15 centers) with questions on attitudes toward biomarkers and biomarker counseling in MCI and dementia. This included postbiomarker counseling and the process of diagnostic disclosure of MCI, as well as treatment and follow-up in MCI., Results: The response rate for the survey was 80.9% (34 of 42 centers) across 20 countries. A large majority of physicians had access to biomarkers and found them useful. Pre- and postbiomarker counseling varied across centers, as did practices for referral to support groups and advice on preventive strategies. Less than half reported discussing driving and advance care planning with patients with MCI., Conclusions: The variability in clinical practices across centers calls for better biomarker counseling and better training to improve communication skills. Future initiatives should address the importance of communicating preventive strategies and advance planning., (© 2020 John Wiley & Sons Ltd.)

Background: The aim of the project was to identify risk factors associated with visual progression and treatment indications in pediatric patients with neurofibromatosis type 1 associated optic pathway glioma (NF1-OPG)., Methods: A multidisciplinary expert group consisting of ophthalmologists, pediatric neuro-oncologists, neurofibromatosis specialists, and neuro-radiologists involved in therapy trials assembled a cohort of children with NF1-OPG from 6 European countries with complete clinical, imaging, and visual outcome datasets. Using methods developed during a consensus workshop, visual and imaging data were reviewed by the expert team and analyzed to identify associations between factors at diagnosis with visual and imaging outcomes., Results: Eighty-three patients (37 males, 46 females, mean age 5.1 ± 2.6 y; 1-13.1 y) registered in the European treatment trial SIOP LGG-2004 (recruited 2004-2012) were included. They were either observed or treated (at diagnosis/after follow-up).In multivariable analysis, factors present at diagnosis associated with adverse visual outcomes included: multiple visual signs and symptoms (adjusted odds ratio [adjOR]: 8.33; 95% CI: 1.9-36.45), abnormal visual behavior (adjOR: 4.15; 95% CI: 1.20-14.34), new onset of visual symptoms (adjOR: 4.04; 95% CI: 1.26-12.95), and optic atrophy (adjOR: 3.73; 95% CI: 1.13-12.53). Squint, posterior visual pathway tumor involvement, and bilateral pathway tumor involvement showed borderline significance. Treatment appeared to reduce tumor size but improved vision in only 10/45 treated patients. Children with visual deterioration after primary observation are more likely to improve with treatment than children treated at diagnosis., Conclusions: The analysis identified the importance of symptomatology, optic atrophy, and history of vision loss as predictive factors for poor visual outcomes in children with NF1-OPG., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Background: Behavioral and psychological symptoms of dementia (BPSD) are quite challenging problems during the dementia course. Special Care Units for people with dementia (PwD) and BPSD (SCU-B) are residential medical structures, where BPSD patients are temporarily admitted, in case of unmanageable behavioral disturbances at home., Objective: RECage (REspectful Caring for AGitated Elderly) aspires to assess the short and long-term effectiveness of SCU-Bs toward alleviating BPSD and improving the quality of life (QoL) of PwD and their caregivers., Methods: RECage is a three-year, prospective study enrolling 500 PwD. Particularly, 250 community-dwelling PwDs presenting with severe BPSD will be recruited by five clinical centers across Europe, endowed with a SCU-B, for a short period of time; a second similar group of 250 PwD will be followed by six other no-SCU-B centers solely via outpatient visits. RECage's endpoints include short and long-term SCU-B clinical efficacy, QoL of patients and caregivers, cost-effectiveness of the SCU-B, psychotropic drug consumption, caregivers' attitude toward dementia, and time to nursing home placement., Results: PwD admitted in SCU-Bs are expected to have diminished rates of BPSD and better QoL and their caregivers are also expected to have better QoL and improved attitude towards dementia, compared to those followed in no-SCU-Bs. Also, the cost of care and the psychotropic drug consumption are expected to be lower. Finally, PwD followed in no-SCU-Bs are expected to have earlier admission to nursing homes., Conclusion: The cohort study results will refine the SCU-B model, issuing recommendations for implementation of SCU-Bs in the countries where they are scarce or non-existent.

Introduction: Many studies, including the HYENA and the DEBATS studies, showed a significant association between aircraft noise exposure and the risk of hypertension. Few studies have considered aircraft noise annoyance and noise sensitivity as factors of interest, especially in relation to hypertension risk, or as mediating or modifying factors. The present study aims 1) to investigate the risk of hypertension in relation to aircraft noise annoyance or noise sensitivity; and 2) to examine the role of modifier or mediator of these two factors in the association between aircraft noise levels and the risk of hypertension., Methods: This study included 6,105 residents of ten European airports from the HYENA and DEBATS studies. Information on aircraft noise annoyance, noise sensitivity, and demographic, socioeconomic and lifestyle factors was collected during an interview performed at home. Participants were classified as hypertensive if they had either blood pressure levels above the WHO cut-off points or physician-diagnosed hypertension in conjunction with the use of antihypertensive medication. Outdoor aircraft noise exposure was estimated for each participant's home address. Poisson regression models with adjustment for potential confounders were used. Interactions between noise exposure and country were tested to consider possible differences between countries., Results: An increase in aircraft noise levels at night was weekly but significantly associated with an increased risk of hypertension (RR = 1.03, 95% CI 1.01-1.06 for a 10-dB(A) increase in L night ). A significant association was found between aircraft noise annoyance and hypertension risk (RR = 1.06, 95%CI 1.00-1.13 for highly annoyed people compared to those who were not highly annoyed). The risk of hypertension was slightly higher for people highly sensitive to noise compared to people with low sensitivity in the UK (RR = 1.29, 95%CI 1.05-1.59) and in France (RR = 1.11, 95%CI 0.68-1.82), but not in the other countries. The association between aircraft noise levels and the risk of hypertension was higher among highly sensitive participants (RR = 1.00, 95%CI 0.96-1.04; RR = 1.03, 95%CI 0.90-1.11; RR = 1.12, 95%CI 1.01-1.24, with a 10-dB(A) increase in L night for low, medium, and high sensitive people respectively) or, to a lesser extent, among highly annoyed participants (RR = 1.06, 95%CI 0.95-1.18 for a 10-dB(A) increase in L night among highly annoyed participants, and RR = 1.02, 95%CI 0.99-1.06 among those not highly annoyed)., Conclusions: The present study confirms findings in the small number of available studies to date suggesting adverse health effects associated with aircraft noise annoyance and noise sensitivity. The findings also indicate possible modifier effects of aircraft noise annoyance and noise sensitivity in the relationship between aircraft noise levels and the risk of hypertension. However, further investigations are needed to better understand this role using specific methodology and tools related to mediation analysis and causal inference., (Copyright © 2020. Published by Elsevier Inc.)