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This study investigates the views of contemporary Muslim jurists about withdrawing treatment of the terminally ill. Its aim is threefold. Firstly, it analyses jurists' views concerning core themes within the process of withdrawing treatment. Secondly, it provides insight into fatwas about withdrawing treatment. Thirdly, it compares these views with current medical standards in Europe and the Atlantic world on withdrawing treatment. The data consisted of six papers by Muslim jurists presented at the conference of the Islamic Fiqh Council in 2015. We conducted a directed content analysis (DCA) through a predetermined framework and compiled an overview of all previous fatwas referred to in the papers, which are also analysed. The results show that the general consensus is that if health cannot be restored, treatment may be withdrawn at the request of the patient and/or his family or on the initiative of the doctor. The accompanying fatwa emphasizes the importance of life-prolonging treatment if this does not harm the patient. It becomes apparent in the fatwa that the doctor has the monopoly in decision-making, which is inconsistent with current medical standards in Europe. Managing disclosure in view of the importance of maintaining the hope of Muslim patients may challenge the doctor's obligation to share a diagnosis with them., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Incisional hernia (IH) is one of the most common complications after abdominal surgeries and may bring great suffering to patients. This study aims to evaluate the global trends in IH research from 2003 to 2023 and visualize the frontiers using bibliometric analysis., Methods: The literature search was conducted on the Web of Science for IH studies published from 2003 to 2023 and sorted by citation frequency. The top 100 most-cited articles were analyzed by the annual publication number, prolific countries and institutions, influential author and journal, and the number of citations through descriptive statistics and visualization., Results: The top paper was cited 1075 times and the median number of citations was 146. All studies were published between 2003 and 2019 and the most prolific year was 2003 with 14 articles. Jeekel J and Rosen M were regarded as the most productive authors with ten articles each and acquired 2738 and 2391 citations, respectively. The top three institutions with the most productive articles were Erasmus Mc, Carolinas Med Ctr, and Univ Utah, while the top three countries were the United States, Netherlands and Germany. The most frequent keyword was "incisional hernia" with 55 occurrences, followed by "mesh repair", "randomized controlled trial", and "polypropylene"., Conclusion: The 100 most-cited papers related to IH were published predominantly by USA and European countries, with randomized controlled trial (RCT) and observational study designs, addressing topics related to risk factors, complications, mesh repair, and mesh components., (© 2023. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Psychodermatology is a subspecialty of dermatology that is of increasing interest to dermatologists and patients. The case for the provision of at least regional psychodermatology services across Europe is robust. Psychodermatology services have been shown to have better, quicker and more cost-efficient clinical outcomes for patients with psychodermatological conditions. Despite this, psychodermatology services are not uniformly available across Europe. In fact many countries have yet to establish dedicated psychodermatology services. In other countries psychodermatology services are in development. Even in countries where psychodermatolgy units have been established, the services are not available across the whole country. This is especially true for the provision of paediatric psychodermatology services. Also whilst most states across Europe are keen to develop psychodermatology services, the rate at which this development is being implemented is very slow. Our paper maps the current provision of psychodermatology services across Europe and indicates that there is still very much more work to be done in order to develop the comprehensive psychodermatology services across Europe, which are so crucial for our patients., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Purpose: To assess the extent of paper waste generated per year by instructions for use (IFUs) brochures included in intraocular lens (IOL) packaging in Europe and the U.S., Setting: Rothschild Foundation Hospital, Paris, France; Royal Free London NHS Foundation Trust; Center for Sight, London, United Kingdom., Design: Experimental study., Methods: A sample of IOLs were collected and each IFU was weighed. In addition, the cumulative weight of these brochures used in cataract surgeries performed annually in Europe and the U.S. was estimated, and the potential annual paper conservation that could be achieved if all manufacturers adopted electronic IFUs (e-IFUs) in Europe and the U.S. was determined., Results: The mean and standard deviation of the weight for overall IFUs, classic IFUs, and e-IFUs were 17.6 ± 13.8 g, 23.5 ± 13.2 g, and 2.9 ± 1.9 g, respectively. The estimated cumulative weight of paper generated from the IFUs accompanying implants used in European and U.S. cataract surgeries is 153 tons. If all manufacturers transition to e-IFUs, the cumulative weight saved would be 128 tons (-84%), equivalent to 120 tons of carbon dioxide equivalent and the preservation of more than 2000 trees annually., Conclusions: The classic IFUs in IOL packaging result in a significant amount of paper waste annually. Therefore, there is an urgent need for a rapid transition to e-IFU technology. The adoption of e-IFUs has already been authorized in Europe and the U.S., and it is crucial to expedite this process., (Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

The growing prevalence and burden of Alzheimer's disease has catalysed huge investments in research on its causes, diagnosis, treatment and care. After many high-profile failures, recent clinical trials of anti-amyloid drugs have marked a turning point for the field, leading to the approval of the first disease-modifying therapies for Alzheimer's disease by the FDA. It is now up to European regulators to determine whether there is sufficient evidence to approve these drugs for patients with mild cognitive impairment or mild dementia due to Alzheimer's disease. Here, we outline Alzheimer Europe's position on anti-amyloid therapies for Alzheimer's disease, which was adopted by the Board of Alzheimer Europe following consultations with our member associations and with the European Working Group of People with Dementia. Beyond questions of drug efficacy, safety and cost, we highlight important issues that must be addressed by industry, regulators, payers, healthcare systems and governments, to ensure that patients have timely, appropriate and equitable access to innovative treatments, regardless of their socio-economic background, insurance status, or place of residence. We also call for continued investment in research on treatments that might benefit people with more advanced Alzheimer's disease - as well as support and care services that can help people live well with dementia at all stages of the disease., Competing Interests: Angela Bradshaw and Jean Georges are employees of Alzheimer Europe, which has received grants from the European Union’s Health, Horizon Europe and Citizens, Equality, Rights and Values programme (CERV) programmes, the Innovative Health Initiative, the Joint Programme for Neurodegenerative Disease Research (JPND) and the Luxembourg Fonds National de la Recherche, as well as sponsorship and support from AbbVie, Biogen, Eisai, Essity, Fujirebio, GE Healthcare, Grifols, Janssen, Lilly, MSD, Novo Nordisk, Nutricia, Prothena, Roche and TauRx.

Cesarean delivery rates are rapidly increasing in Southeastern Europe (to more than 60%), North Africa (with a rate as high as 72% in Egypt), and in urban areas in Southern Africa (a rate of over 50% in Lagos, Nigeria). Data on the background to these increases are scarce, but likely to include poor birthing facilities in general hospitals, convenience for the doctor, private medicine, fear of litigation, socioeconomic status, shortage of midwives and nurses, and disappearance of vaginal instrumental deliveries. Options to reverse cesarean delivery trends are discussed. In this context there is a need to be better informed about how women are being counseled regarding vaginal or cesarean delivery. The long-term consequences in subsequent pregnancies for mothers and children may well be largely ignored, while these risks are highest in LMICs where higher birth numbers are desired. FIGO has begun discussions with obstetric and gynecologic societies, healthcare bodies, and governments in several countries discussed in this article, to find ways to lower the cesarean delivery rate. The requests came from the countries themselves, which may prove beneficial in helping advance progress., (© 2023 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

A large proportion of the world's disease burden is attributable to mental illnesses. Although effective interventions are available, many patients still have limited access to evidence-based treatments. Aside from access, treatment gaps, including inappropriate medication selection and monitoring, are also routinely recognised. Mental health clinical pharmacists can help address these gaps and enable patients to receive optimised pharmaceutical care, particularly appropriate medication selection and monitoring. The European Society of Clinical Pharmacy (ESCP) Special Interest Group on Mental Health was established to improve standardised service provision in mental health settings across Europe. The Special Interest Group identified significant barriers (predominantly associated with reimbursement and position within the multidisciplinary team) to effective pharmaceutical care amongst those with mental illnesses. This commentary presents recommendations to address these gaps through improved mental health clinical pharmacy service provision., (© 2023. The Author(s).)

Non-native species are spreading at an unprecedented rate over large spatial scales, with global environmental change and growth in commerce providing novel opportunities for range expansion. Assessing the pattern and rate of spread is key to the development of strategies for safeguarding against future invasions and efficiently managing existing ones. Such assessments often depend on spatial distribution data from online repositories, which can be spatially biased, imprecise, and lacking in quantity. Here, the influence of disparities between occurrence records from online data repositories and what is known of the invasion history from peer-reviewed published literature on non-native species range expansion was evaluated using 6693 records of the Pacific oyster, Magallana gigas (Thunberg, 1793), spanning 56 years of its invasion in Europe. Two measures of spread were calculated: maximum rate of spread (distance from introduction site over time) and accumulated area (spatial expansion). Results suggest that despite discrepancies between online and peer-reviewed data sources, including a paucity of records from the early invasion history in online repositories, the use of either source does not result in significantly different estimates of spread. Our study significantly improves our understanding of the European distribution of M. gigas and suggests that a combination of short- and long-range dispersal drives range expansions. More widely, our approach provides a framework for comparison of online occurrence records and invasion histories as documented in the peer-reviewed literature, allowing critical evaluation of both data sources and improving our understanding of invasion dynamics significantly., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, Switzerland)., (© 2021. The Author(s).)

Bisphenol A (BPA) is used as a color developer in a thermal paper that after a heating process reacts with a leuco dye and changes it to a colored form. Receipts from cash registers are considered as the main source of consumer exposure to bisphenols together with polycarbonates and epoxy resins. Levels of BPA and its possible alternatives were determined in thermal paper samples collected between May 2018 and May 2019 in 22 European and 17 non-European countries on all inhabited continents (220 samples in total, 133 of which were from Europe and 87 from other countries). These measurements were intended to check the level of BPA presence in receipts originating from different countries, especially from Europe in the light of changing regulations restricting its use. The effect of thermal printing on developer content was also analyzed, but no major changes in concentrations of bisphenols were observed during the process. Thus, printed receipts could be used for the determination of bisphenol content. Analysis of receipts from 39 countries has shown that BPA is still the most common compound used around the world with 69% samples containing this color developer. Among other tested bisphenols, BPS was used as a color developer in 20% samples, but it was noted that all samples collected from Japan and the United States of America were found to contain only BPS. Other bisphenols (F, AF, E, and B) considered as possible alternatives for BPA were detected only at trace levels or not detected at all, which showed that they were not used as color developers. The relatively large use of BPS as a BPA substitute is worrying because this compound not only has similar endocrine properties but is also poorly biodegradable. Besides, its relatively high polarity facilitates spreading in the environment., 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 © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Gastro-oesophageal reflux (GOR) and food allergy (FA) are common conditions, especially during the first 12 months of life. When GOR leads to troublesome symptoms, that affect the daily functioning of the infant and family, it is referred to as GOR disease (GORD). The role of food allergens as a cause of GORD remains controversial. This European Academy of Allergy and Clinical Immunology (EAACI) position paper aims to review the evidence for FA-associated GORD in young children and translate this into clinical practice that guides healthcare professionals through the diagnosis of suspected FA-associated GORD and medical and dietary management. The task force (TF) on non-IgE mediated allergy consists of EAACI experts in paediatric gastroenterology, allergy, dietetics and psychology from Europe, United Kingdom, United States, Turkey and Brazil. Six clinical questions were formulated, amended and approved by the TF to guide this publication. A systematic literature search using PubMed, Cochrane and EMBASE databases (until June 2021) using predefined inclusion criteria based on the 6 questions was used. The TF also gained access to the database from the European Society of Paediatric Gastroenterology and Hepatology working group, who published guidelines on GORD and ensured that all publications used within that position paper were included. For each of the 6 questions, practice points were formulated, followed by a modified Delphi method consisting of anonymous web-based voting that was repeated with modified practice points where required, until at least 80% consensus for each practice point was achieved. This TF position paper shares the process, the discussion and consensus on all practice points on FA-associated GORD., (© 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Introduction: Adolescence is a critical stage of rapid biological, emotional and social change and development. Adolescents and young adults (AYA) with asthma and allergies need to develop the knowledge and skills to self-manage their health independently. Healthcare professionals (HCP), parents and their wider network play an essential role in supporting AYA in this process. Previous work showed significant limitations in transition care across Europe. In 2020, the first evidence-based guideline on effective transition for AYA with asthma and allergies was published by EAACI., Aim: We herein summarize practical resources to support this guideline's implementation in clinical practice., Methods: For this purpose, multi-stakeholder Task Force members searched for resources in peer review journals and grey literature. These resources were included if relevant and of good quality and were pragmatically rated for their evidence-basis and user friendliness., Results: Resources identified covered a range of topics and targeted healthcare professionals, AYA, parents/carers, schools, workplace and wider community. Most resources were in English, web-based and had limited evidence-basis., Conclusions: This position paper provides a valuable selection of practical resources for all stakeholders to support effective transitional care for AYA with asthma and allergies. Future research should focus on developing validated, patient-centred tools to further assist evidence-based transition care., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

The increasing use in clinical practice of software such as mobile apps and clinical decision support (CDS) software has only recently been taken up by regulators around the world. Specifically, the European Commission and the US Food and Drug Administration (FDA) have updated their regulatory framework in the last years. Van Laere et al have given an extensive overview of the European and US approaches to regulate CDS software. This commentary further discusses regulatory differences between the two geographies and their impact on manufacturers of medical device software. We discuss the practical implementation of the regulatory framework for medical device software (especially CDS software) with a reference to the available international guidance documents and their limitations. Given the direction of stricter regulatory oversight in Europe, additional European guidelines/examples are desirable to enable a pragmatic regulatory approach ensuring continued access to innovative medical device software for European patients., (© 2023 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Economic regulation is an instrument of the state or other institutions to correct market failures, rectify the business environment, or protect consumers. Regulation can be a major driver of innovation, and it has proven to be so in the past. On the other hand, there are also documented cases of ineffective regulation due to information delays or shortcomings in government decision-making. The complexity of the impact of regulatory changes on innovation can currently be observed in the medical device market in Europe. Regulation (EU) 2017/745 whose main idea is to ensure greater safety and health protection for consumers, is a challenge for originator, manufacturer, mostly small and medium-sized enterprises. The regulation is associated with an increase in the cost of developing and maintaining the product on the market. We can now gradually begin to analyze whether it can be ranked among those that have become drivers of innovation., (© 2023 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background and Aims: This bibliometric analysis aims to analyze the high-cited papers (HCPs), those which have received >100 citations) on Sarcopenia to provide insight into publication performances and research characteristics of the literature., Methods: Global HCPs on Sarcopenia research were identified from the Scopus database from January 1993 to August 2022. VOSviewer, and Biblioshiny software were used to visualize the collaborative interaction among most productive countries, organizations, authors, and keywords. Select bibliometric measures were applied to evaluate the publication productivity and their influence in this area., Results: Out of 6219 publications on Sarcopenia only 398 were HCPs. These HCPs received an average of 271.7 citations per publication (CPP). The most productive organizations were the Università Cattolica del Sacro Cuore, Italy, and Jean Mayer USDA Human Nutrition Center on Aging, USA. The most impactful organizations in terms of CPP and relative citation index were CHU de Toulouse, France, and Università Cattolica del Sacro Cuore, Italy. The most productive authors were Landi F and Morley JE, and Anker SD from Italy and Germany respectively. The most impactful authors were: Cederholm T (Sweden), Cruz JAJ (Spain) and Rolland Y (France). There were few/no HCPs from South America, Africa, South Asia, and USSR., Conclusion: Sarcopenia research has been predominantly done in USA, Europe, and China, and rarely from low and middle-income countries. Further focus of research should be on its etiopathogenesis (especially at the molecular level), prevalence in different communities, methods to diagnose it in early stages, and its cost-effective management., Competing Interests: Declaration of competing interest Authors #1 (RV), and 3 (AM) are of the Editorial board of DMSCRR., (Copyright © 2022 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Heart failure (HF) is a long-term clinical syndrome, with increasing prevalence and considerable healthcare costs that are further expected to increase dramatically. Despite significant advances in therapy and prevention, mortality and morbidity remain high and quality of life poor. Epidemiological data, that is, prevalence, incidence, mortality, and morbidity, show geographical variations across the European countries, depending on differences in aetiology, clinical characteristics, and treatment. However, data on the prevalence of the disease are scarce, as are those on quality of life. For these reasons, the ESC-HFA has developed a position paper to comprehensively assess our understanding of the burden of HF in Europe, in order to guide future policies for this syndrome. This manuscript will discuss the available epidemiological data on HF prevalence, outcomes, and human costs-in terms of quality of life-in European countries., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Spinal dysraphism (SD) or spina bifida (SB) is a congenital deformity that results from embryonic neural tube closure failure during fetal development. This evidence-based position paper represents the official position of the European Union through the UEMS PRM Section. This paper aims to evaluate the role of the physical and rehabilitation medicine (PRM) physician and PRM practice for children and adults with spinal dysraphism. A systematic literature review and a consensus procedure involved all European countries delegates represented in the UEMS PRM section through a Delphi process. The systematic literature review is reported together with thirty-two recommendations resulting from the Delphi procedure. The professional role of the PRM physician requires specific expertise in the treatment of patients with SD to plan, lead and monitor the rehabilitation process in an interdisciplinary setting and to participate in the assessment of the needs of these patients in the transitional phase from childhood to adulthood, with particular attention to the activity limitation and participation restriction.

Management of datasets that include health information and other sensitive personal information of European study participants has to be compliant with the General Data Protection Regulation (GDPR, Regulation (EU) 2016/679). Within scientific research, the widely subscribed'FAIR' data principles should apply, meaning that research data should be findable, accessible, interoperable and re-usable. Balancing the aim of open science driven FAIR data management with GDPR compliant personal data protection safeguards is now a common challenge for many research projects dealing with (sensitive) personal data. In December 2020 a workshop was held with representatives of several large EU research consortia and of the European Commission to reflect on how to apply the FAIR data principles for environment and health research (E&H). Several recent data intensive EU funded E&H research projects face this challenge and work intensively towards developing solutions to access, exchange, store, handle, share, process and use such sensitive personal data, with the aim to support European and transnational collaborations. As a result, several recommendations, opportunities and current limitations were formulated. New technical developments such as federated data management and analysis systems, machine learning together with advanced search software, harmonized ontologies and data quality standards should in principle facilitate the FAIRification of data. To address ethical, legal, political and financial obstacles to the wider re-use of data for research purposes, both specific expertise and underpinning infrastructure are needed. There is a need for the E&H research data to find their place in the European Open Science Cloud. Communities using health and population data, environmental data and other publicly available data have to interconnect and synergize. To maximize the use and re-use of environment and health data, a dedicated supporting European infrastructure effort, such as the EIRENE research infrastructure within the ESFRI roadmap 2021, is needed that would interact with existing infrastructures., (Copyright © 2022. Published by Elsevier Ltd.)

Background and Purpose: This position paper makes recommendations following an audit of care provided to people presenting with a seizure to emergency departments (EDs) in Europe., Methods: Participating countries were asked to include five hospitals agreeing to identify 50 consecutive seizure patients presenting to their ED between 1 August 2016 and 31 August 2017. Anonymous data were collected to a web database. Where quoted, percentages are mean site values and ranges are the 10th-90th centile., Results: Data were collected on 2204 ED visits (47 sites, up to six per country, across 15 countries): 1270 (58%) known epilepsy, 299 (14%) previous blackouts but no epilepsy diagnosis, 634 (29%) with a first seizure. Wide variability was identified for most variables. Of those with known epilepsy, 41.2% (range 26.2%-59.6%) attended the ED in the previous 12 months, but only 64.7% (range 37.2%-79.8%) had seen an epilepsy specialist in the previous 12 months. 67.7% (range 34.0%-100%) were admitted, 53.1% to a neurology ward (range 0.0%-88.9%). Only 37.5% first seizure patients (range 0.0%-71.4%) were given advice about driving., Conclusions and Recommendations: It is recommended that in Europe guidance is agreed on the management and onward referral of those presenting to the ED with a seizure; a referral process is created that can be easily implemented; it is ensured that the seizure services receive referrals and see the patients within a short time period; and a simple system is developed and implemented to allow continuous monitoring of key indices of epilepsy care., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Following the fast spread of Covid-19 across Europe and North America in March 2020, many people started stockpiling commodities like toilet paper. Despite the high relevance for public authorities to adequately address stockpiling behavior, empirical studies on the psychological underpinnings of toilet paper stockpiling are still scarce. In this study, we investigated the relation between personality traits, perceived threat of Covid-19, and stockpiling of toilet paper in an online survey (N = 996) across 22 countries. Results suggest that people who felt more threatened by Covid-19 stockpiled more toilet paper. Further, a predisposition towards Emotionality predicted the perceived threat of Covid-19 and affected stockpiling behavior indirectly. Finally, Conscientiousness was related to toilet paper stockpiling, such that individuals higher in Conscientiousness tended to stockpile more toilet paper. These results emphasize the importance of clear communication by public authorities acknowledging anxiety and, at the same time, transmitting a sense of control., Competing Interests: The authors have declared that no competing interests exist.

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease that affects both upper and lower motor neurons and is fatal in its course. This evidence-based position paper represents the official position of the UEMS PRM Section. The aim of the paper is to define the role of the physical and rehabilitation medicine (PRM) physician and PRM professional practice for people with ALS. A systematic review of the literature and a consensus procedure by means of a Delphi process have been performed involving the delegates of all European countries represented in the UEMS PRM Section. The systematic literature review is reported together with thirty-two recommendations resulting from the Delphi procedure. The responsibility of the PRM physician is functional assessment of persons with ALS and delivering the optimal and most effective PRM program of care. The rehabilitation program of patients with ALS should be delivered and monitored by the multiprofessional team, with the PRM physician as principal coordinator.

Extracellular vesicles (EV) are emergent therapeutic effectors that have reached clinical trial investigation. To translate EV-based therapeutic to clinic, the challenge is to demonstrate quality, safety, and efficacy, as required for any medicinal product. EV research translation into medicinal products is an exciting and challenging perspective. Recent papers, provide important guidance on regulatory aspects of pharmaceutical development, defining EVs for therapeutic applications and critical considerations for the development of potency tests. In addition, the ISEV Task Force on Regulatory Affairs and Clinical Use of EV-based Therapeutics as well as the Exosomes Committee from the ISCT are expected to contribute in an active way to the development of EV-based medicinal products by providing update on the scientific progress in EVs field, information to patients and expert resource network for regulatory bodies. The contribution of our work group "Extracellular Vesicle translatiOn to clinicaL perspectiVEs - EVOLVE France", created in 2020, can be positioned in complement to all these important initiatives. Based on complementary scientific, technical, and medical expertise, we provide EV-specific recommendations for manufacturing, quality control, analytics, non-clinical development, and clinical trials, according to current European legislation. We especially focus on early phase clinical trials concerning immediate needs in the field. The main contents of the investigational medicinal product dossier, marketing authorization applications, and critical guideline information are outlined for the transition from research to clinical development and ultimate market authorization., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Florence Gazeau, Amanda Karine Andriola Silva, Claire Wilhelm and Gabriel Rahmi are co-founders of the spin-off Evora Biosciences. Amanda Karine Andriola Silva and Claire Wilhelm are co-founders of the spin-off EverZom. Max Piffoux is consultant and owns stocks in the spin-off Evora Biosciences and in the spin-off EverZom., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Muscular dystrophies present a group of inherited degenerative disorder that are characterized by progressive muscular weakness. This evidence-based position paper represents the official position of the European Union through the UEMS PRM Section. The aim of the paper is to evaluate the role of the physical and rehabilitation medicine (PRM) physician and PRM practice for people with muscular dystrophies. A systematic review of the literature and a consensus procedure by means of a Delphi process have been performed involving the delegates of all European countries represented in the UEMS PRM Section. The systematic literature review is reported together with thirty-three recommendations resulting from the Delphi procedure. The role of the PRM physician is to assess the functional status of persons with muscular dystrophy and to plan, monitor and lead PRM program in an interdisciplinary setting within a multiprofessional team.

Cerebral palsy (CP) is a group of the most common developmental disorders affecting movement and posture of the body, causing activity limitations and participation restrictions. The motor disorders of persons with CP are often accompanied by disturbances of sensation, cognition, communication and perception. The symptoms of CP are very diverse and persons with CP are usually presented with a mixed type of symptoms. The non-progressive disturbances can be attributed to disorders that were developed during pregnancy, birth and/or infant stage. The aim of this study was to improve physicians' professional practice of Physical and Rehabilitation Medicine for persons with cerebral palsy in order to improve their functionality, social and community integration, and to reduce activity limitations and/or participation restrictions. A systematic review of the literature including an 18-year period and consensus procedure by means of a Delphi process was performed and involved the delegates of all European countries represented in the Union of European Medical Specialists Physical and Rehabilitation Medicine (UEMS PRM) Section. As the result of a Consensus Delphi procedure, 74 recommendations are presented together with the systematic literature review. The PRM physician's role for persons with cerebral palsy is to lead and coordinate the multiprofessional team, working in an interdisciplinary way. They should propose and manage the complex but individual PRM program developed in conjunction with other health professionals, medical specialists and importantly in agreement with the patient, their family and care giver. This should be, according to the specific medical diagnosis to improve patients' health, functioning, social and education status, considering all impairments, comorbidities and complications, activity limitations and participation restrictions. This evidence-based position paper is representing the official position of The European Union through the UEMS PRM Section and designates the professional role of PRM physicians in persons with cerebral palsy.

Background: The WHO definition of palliative care includes bereavement support as integral to palliative care, yet a previous survey of bereavement support in palliative care in Europe has shown a range of service responses to loss. A rigorous approach to agreeing and implementing a palliative care bereavement framework was required., Aim: The aim of this study was to develop consensus on best-practice recommendations for bereavement care principles, structures, processes and delivery based on current practice and evidence., Design: In accordance with Guidance on Conducting and Reporting Delphi Studies, a consensus-building five-round Delphi technique was performed. A scoping review of research literature informed drafting of 54 statements by the EAPC Bereavement Task Force. Evaluation of the statements was performed by an expert panel using a 5-point Likert scale. ⩾80% agreement were defined as essential items and 75%-79% agreement were defined as desirable items. Items with a consensus rating <75% were revised during the process., Setting/participants: The Delphi study was carried out by an expert panel among membership organisations of the European Association for Palliative Care., Results: In total, 376 email requests to complete Delphi questionnaire were distributed with a response rate of 23% ( n = 87) and a follow-up response-rate of 79% ( n = 69). Of the initial 54 statements in six dimensions, 52 statements were endorsed with 26 essential statements and 26 desirable statements., Conclusions: The six dimensions and 52 statements agreed through this Delphi study clarify a coherent direction for development of bereavement services in palliative care in Europe.

Aims: To examine the current status of care and needs of adult congenital heart disease (ACHD) services in the Central and South Eastern European (CESEE) region., Methods and Results: We obtained data regarding the national ACHD status for 19 CESEE countries from their ACHD representative based on an extensive survey for 2017 and/or 2018. Thirteen countries reported at least one tertiary ACHD centre with a median year of centre establishment in 2007 (interquartile range 2002-2013). ACHD centres reported a median of 2114 patients under active follow-up with an annual cardiac catheter and surgical intervention volume of 49 and 40, respectively. The majority (90%) of catheter or surgical interventions were funded by government reimbursement schemes. However, all 19 countries had financial caps on a hospital level, leading to patient waiting lists and restrictions in the number of procedures that can be performed. The median number of ACHD specialists per country was 3. The majority of centres (75%) did not have ACHD specialist nurses. The six countries with no dedicated ACHD centres had lower Gross Domestic Product per capita compared to the remainder (P = 0.005)., Conclusion: The majority of countries in CESEE now have established ACHD services with adequate infrastructure and a patient workload comparable to the rest of Europe, but important gaps still exist. ACHD care is challenged or compromised by limited financial resources, insufficient staffing levels, and reimbursement caps on essential procedures compared to Western Europe. Active advocacy and increased resources are required to address the inequalities of care across the continent., (© 2020 European Society of Cardiology.)

Waste paper, an essential substitute for wood and other plant-based fibers in paper making, is an indispensable part of the circular economy; yet, the impacts of China's ban on global waste paper cycles have not been well understood. We modeled the evolution of the global waste paper trade network during 1995-2019. We found that the cumulative trade volume of global waste paper reached 1010 million tons in the last 25 years and showed a downward trend since 2015. The global import center of waste paper experienced a transfer from Europe to East Asia and then to Southeast Asia. The ban has stimulated some developed countries to reduce the exports of unsorted waste paper since 2017, but for many major importers their changes in waste paper trade patterns were related to waste paperboard, which was not banned by China, suggesting that this import change trend may be inevitable and irrespective of China's ban. Besides, India has replaced China to become a new import hub of unsorted waste paper. Our results lay a foundation for exploring the evolution of the future global solid waste cycle under the background of zero import of solid waste increasingly implemented by China and many other developing countries.

Background: Pancreatic ductal adenocarcinoma is the deadliest cancer worldwide with a 98% loss-of-life expectancy and a 30% increase in the disability-adjusted life years during the last decade in Europe. The disease cannot be effectively prevented nor being early detected. When diagnosed, 80% of patients have tumors that are in incurable stages, while for those who undergo surgery, 80% of patients will present with local or distant metastasis. Importantly, chemotherapies are far from being effective., Objective: Pancreatic cancer represents a great challenge and, at the same time, a huge opportunity for advancing our understanding on the basis of the disease, the molecular profiles, that would lead to develop tools for early detection and effective treatments, thus, boosting patient survival., Results: Research on pancreatic cancer has being receiving little or minimal funds from European funding bodies. UEG is calling for public-private partnerships that would effectively fund research on pancreatic cancer., Conclusion: This would increase our understanding of this disease and better treatment, through pan-European efforts that take advantage of the strong academic European research landscape on pancreatic cancer, and the contribution by the industry of all sizes., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Objective: This quali-quantitative study analysed the 100 most-cited papers in core dental public health (DPH) journals focusing on understanding international knowledge production., Methods: The DPH journals were selected from titles and scopes at Web of Science Core Collection database up to March 2020. Further comparisons were performed at Scopus and Google Scholar databases. Some bibliometric parameters were extracted as follows: title, number of citations, citation density (number of citations per year), first author's country, year of publication, study design and subject. VOSviewer software was used to create graphical bibliometric maps., Results: Papers were ranked by the total number of citations, which ranged from 104 to 1,019, and six papers were cited more than 400 times. Papers were published from 1974 to 2013, mainly in Community Dentistry and Oral Epidemiology. Most frequent study designs were cross-sectional (30%) and nonsystematic review (25%). Most papers were from Europe (54%) and North America (31%). First authors were predominantly from the United Kingdom (17%), United States of America (17%) and Canada (14%). VOSviewer map of co-authorship demonstrated the existence of clusters in the research collaboration. Although epidemiology was the most frequent subject (84%), health services research presented eight times higher citation density., Conclusions: Top 100 most-cited papers in core DPH journals were predominantly observational studies from Anglo-Saxon countries. Top 100 most-cited papers in core DPH journals tend to be cross-sectional studies carried out in the United States with highest citation in health services research. Locker D, Petersen PE and Sheiham A are a landmark for DPH field., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This paper reports on the recent activity of the pan-European consensus of the ADEE Special Interest Group for Pre-Clinical Operative Skills. Following the previous recommendations from the group, and in order to support teachers and to harmonise the delivery of skills training across Europe, a more formal curriculum relating to pre-clinical operative skills needs to be created. This paper reports European consensus surrounding the categorisation (level of importance, and difficulty) of basic operative dental clinical skills within the undergraduate curriculum and provides recommendations relating to session structure and timing of curricular elements for basic operative dental clinical skills teaching., (© 2020 The Authors. European Journal of Dental Education published by John Wiley & Sons Ltd.)

Purpose: To develop a European White Paper document on oropharyngeal dysphagia (OD) in head and neck cancer (HNC). There are wide variations in the management of OD associated with HNC across Europe., Methods: Experts in the management of specific aspects of OD in HNC across Europe were delegated by their professional medical and multidisciplinary societies to contribute to this document. Evidence is based on systematic reviews, consensus-based position statements, and expert opinion., Results: Twenty-four sections on HNC-specific OD topics., Conclusion: This European White Paper summarizes current best practice on management of OD in HNC, providing recommendations to support patients and health professionals. The body of literature and its level of evidence on diagnostics and treatment for OD in HNC remain poor. This is in the context of an expected increase in the prevalence of OD due to HNC in the near future. Contributing factors to increased prevalence include aging of our European population (including HNC patients) and an increase in human papillomavirus (HPV) related cancer, despite the introduction of HPV vaccination in various countries. We recommend timely implementation of OD screening in HNC patients while emphasizing the need for robust scientific research on the treatment of OD in HNC. Meanwhile, its management remains a challenge for European professional associations and policymakers.

Multiple myeloma is the second most common hematological malignancy in the USA and Europe. Despite improvements in the 5-year and overall survival rates over the past decade, older adults (aged ≥65 years) with multiple myeloma continue to experience disproportionately worse outcomes than their younger counterparts. These differences in outcomes arise from the increased prevalence of vulnerabilities such as medical comorbidities and frailty seen with advancing age that can influence treatment-delivery and tolerance and impact survival. In general, geriatric assessments can help identify those patients more likely to benefit from enhanced toxicity risk-prediction and aid treatment decision-making. Despite the observed benefits of geriatric assessments and other screening frailty tools, provider and systems-level barriers continue to influence the overall perception of the feasibility of geriatric assessments in clinical practice settings. Clinical trials are underway evaluating the efficacy and safety of various multiple myeloma therapies in less fit/frail older adults, with a minority examining fitness-based/risk-adapted approaches. Thus, significant gaps exist in knowing which myeloma therapies are most appropriate for older and more vulnerable adults with multiple myeloma. The purpose of this Review is to discuss how geriatric assessments can be used to guide the management of transplant-ineligible patients; and to highlight frontline therapies for standard-risk and high-risk cytogenetic abnormalities [i.e., t(4;14), t(14;16), and del(17p)] associated with multiple myeloma. We also discuss the current shortcomings of the existing clinical approaches to care and highlight ongoing clinical trials evaluating newer fitness-based approaches to managing transplant-ineligible patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

It is well recognised that adolescents and young adults (AYA) with cancer have inequitable access to oncology services that provide expert cancer care and consider their unique needs. Subsequently, survival gains in this patient population have improved only modestly compared with older adults and children with cancer. In 2015, the European Society for Medical Oncology (ESMO) and the European Society for Paediatric Oncology (SIOPE) established the joint Cancer in AYA Working Group in order to increase awareness among adult and paediatric oncology communities, enhance knowledge on specific issues in AYA and ultimately improve the standard of care for AYA with cancer across Europe. This manuscript reflects the position of this working group regarding current AYA cancer care, the challenges to be addressed and possible solutions. Key challenges include the lack of specific biological understanding of AYA cancers, the lack of access to specialised centres with age-appropriate multidisciplinary care and the lack of available clinical trials with novel therapeutics. Key recommendations include diversifying interprofessional cooperation in AYA care and specific measures to improve trial accrual, including centralising care where that is the best means to achieve trial accrual. This defines a common vision that can lead to improved outcomes for AYA with cancer in Europe., Competing Interests: Funding The European Society for Medical Oncology (ESMO) (no grant number) and the European Society for Paediatric Oncology (SIOPE) (no grant number) were the legal sponsors of this position paper. No research funding for the meetings or manuscript preparation was received from any third parties. Disclosure DS reports receipt of research grants from Teenage Cancer Trust. FAP reports personal financial interest as a Scientific Director at the European School of Oncology; receipt of lecture/presentation fees from Prime Oncology and Takeda; receipt of honoraria for advisory board participation/advisory services from Roche, AstraZeneca, Clovis and Ipsen. LF reports receipt of funding from Teenage Cancer Trust. IB-S reports receipt of speaker fees from Roche, Novartis and Pfizer; direct research funding as Principal Investigator from Roche; financial support to institution for clinical trials from Roche. OS reports receipt of honoraria for advisory board participation from Genuity Science. LH reports receipt of speaker fees from Roche. WTAvdG reports receipt of research funding from Novartis, honoraria for advisory board from Bayer and consultancy fees from SpringWorks, all to her institutes. SB reports receipt of honoraria for advisory board participation from Pfizer, Bayer, Lilly, Novartis and Isofol. GM reports receipt of speakers fees from AstraZeneca, Roche, MSD, BMS, Pfizer, Takeda, Janssen, Novartis and Sanofi; receipt of consultancy fees from AstraZeneca, Roche, MSD, BMS, Novartis and Sanofi; direct research funding as Principal Investigator from AstraZeneca, Novartis and MSD; financial support to institution for clinical trials from AstraZeneca, Novartis and MSD. ES reports receipt of honoraria for the provision of advisory services from Roche Hellas, BMS, Pfizer Hellas, AstraZeneca, Amgen Hellas and Dimiourgiki Farmakeutikon Ypiresion AE; receipt of research funding from Astellas Pharma; travel and education support from Roche Hellas, Pfizer Hellas, Astellas Pharma, Novartis (Hellas), MSD Greece and Enorasis. All other authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Timely and effective antithrombotic therapy is critical to improving outcome, including survival, in patients with acute coronary syndrome (ACS). Achieving effective platelet inhibition and anticoagulation, with minimal risk, is particularly important in high-risk ACS patients, especially those with cardiogenic shock (CS) or those successfully resuscitated following out-of-hospital cardiac arrest (OHCA), who have a 30-50% risk of death or a recurrent ischaemic event over the subsequent 30 days. There are unique challenges to achieving effective and safe antithrombotic treatment in this cohort of patients that are not encountered in most other ACS patients. This position paper focuses on patients presenting with CS or immediately post-OHCA, of presumed ischaemic aetiology, and examines issues related to thrombosis and bleeding risk. Both the physical and pharmacological impacts of CS, namely impaired drug absorption, metabolism, altered distribution and/or excretion, associated multiorgan failure, co-morbidities and co-administered treatments such as opiates, targeted temperature management, renal replacement therapy and circulatory or left ventricular assist devices, can have major impact on the effectiveness and safety of antithrombotic drugs. Careful attention to the choice of antithrombotic agent(s), route of administration, drug-drug interactions, therapeutic drug monitoring and factors that affect drug efficacy and safety, may reduce the risk of sub- or supra-therapeutic dosing and associated adverse events. This paper provides expert opinion, based on best available evidence, and consensus statements on optimising antithrombotic therapy in these very high-risk patients, in whom minimising the risk of thrombosis and bleeding is critical to improving outcome., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Diagnostic allergens are defined as medicinal products in the EU. Marketing authorization by national authorities is necessary; however, diagnostic allergens are not homogeneously regulated in different EU member states. Allergen manufacturers argue with increasing costs forcing them to continuously reduce the diagnostic allergen portfolios offered to allergists. In contrast, EAACI and national European Allergy Societies see the need for the availability of a wide range of high-quality diagnostic allergens for in vivo diagnosis of IgE-mediated allergies not only covering predominant but also less frequent allergen sources. In a recent EAACI task force survey, the current practice of allergy diagnosis was shown to rely on skin tests as first option in almost 2/3 of all types of allergic diseases and in 90% regarding respiratory allergies. With the need to ensure the availability of high-quality diagnostic allergens in the EU, an action plan has been set up by EAACI to analyse the current regulatory demands in EU member states and to define possible solutions stated in this document: (a) simplification of authorization for diagnostic allergens; (b) specific regulation of special types of diagnostic allergens; (c) new models beyond the current model of homologous groups; (d) simplification of pharmacovigilance reporting; (e) reduction of regulation fees for diagnostic allergens; (f) reimbursement for diagnostic allergens. Joining forces of allergists, manufacturers and authorities are of high importance to ensure remaining relevant allergens in the EU markets to facilitate a sustainable and comprehensive service for the diagnosis and treatment of allergic diseases., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

In Europe, lung cancer ranks third among the most common cancers, remaining the biggest killer. Since the publication of the first European Society of Radiology and European Respiratory Society joint white paper on lung cancer screening (LCS) in 2015, many new findings have been published and discussions have increased considerably. Thus, this updated expert opinion represents a narrative, non-systematic review of the evidence from LCS trials and description of the current practice of LCS as well as aspects that have not received adequate attention until now. Reaching out to the potential participants (persons at high risk), optimal communication and shared decision-making will be key starting points. Furthermore, standards for infrastructure, pathways and quality assurance are pivotal, including promoting tobacco cessation, benefits and harms, overdiagnosis, quality, minimum radiation exposure, definition of management of positive screen results and incidental findings linked to respective actions as well as cost-effectiveness. This requires a multidisciplinary team with experts from pulmonology and radiology as well as thoracic oncologists, thoracic surgeons, pathologists, family doctors, patient representatives and others. The ESR and ERS agree that Europe's health systems need to adapt to allow citizens to benefit from organised pathways, rather than unsupervised initiatives, to allow early diagnosis of lung cancer and reduce the mortality rate. Now is the time to set up and conduct demonstration programmes focusing, among other points, on methodology, standardisation, tobacco cessation, education on healthy lifestyle, cost-effectiveness and a central registry.Key Points• Pulmonologists and radiologists both have key roles in the set up of multidisciplinary LCS teams with experts from many other fields.• Pulmonologists identify people eligible for LCS, reach out to family doctors, share the decision-making process and promote tobacco cessation.• Radiologists ensure appropriate image quality, minimum dose and a standardised reading/reporting algorithm, together with a clear definition of a "positive screen".• Strict algorithms define the exact management of screen-detected nodules and incidental findings.• For LCS to be (cost-)effective, it has to target a population defined by risk prediction models.

A sensitive and simple nanomaterial based colorimetric sensor array (NBCSA) was developed for discrimination of monofloral honey from various European countries based on three botanical origins as Acacia, Canola and Honeydew. The NBCSA was designed by spotting gold (AuNPs) and silver (AgNPs) nanoparticles synthesized using six different reducing and/or capping agents. The colour intensity of AuNPs represented differential changes when interacting with volatile organic compounds appeared in the headspace of the honey samples. The color difference maps, which are calculated as the difference between color intensity of the sensor before and after exposing to the sample vapors, were used as a fingerprint to discriminate the honey samples based on botanical origin. Classification was achieved utilizing data pre-processing and chemometrics data analysis. Fitting accuracies of 88% and 86% were obtained by partial least squares discriminant analysis and linear discriminant analysis whereas 100% was achieved using support vector machine., 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 © 2020 Elsevier B.V. All rights reserved.)

Background: The development of new genetic testing methods and the approval of the first treatments raises questions regarding when and how to perform screening for inherited neuromuscular conditions. Screening directives and access to the different techniques is not uniform across Europe. The patient advisory board of the European reference network for rare neuromuscular diseases (NMD) conducted a qualitative study to understand the state of play of screening for inherited NMD in Europe and patients' needs., Results: We collected answers from 30 patient organisations (POs) from 18 European countries. Fifteen acknowledge the existence of pre-implantation genetic diagnosis in their country. Regarding prenatal screening, we had 25 positive answers and 5 negative ones. Twenty-four POs mentioned that newborn screening was available in their country. We had some contradictory answers from POs from the same country and in some cases; diseases said to be part of the screening programmes were not hereditary disorders. Twenty-eight organisations were in favour of screening tests. The reasons for the two negative answers were lack of reimbursement and treatment, religious beliefs and eventual insurance constrains. Most POs (21) were in favour of systematic screening with the option to opt-out. Regarding the timing for screening, "at birth", was the most consensual response. The main priority to perform screening for NMDs was early access to treatment, followed by shorter time to diagnostic, preventive care and genetic counselling., Conclusions: This is the first study to assess knowledge and needs of POs concerning screening for NMDs. The knowledge of POs regarding screening techniques is quite uneven. This implies that, even in communities highly motivated and knowledgeable of the conditions they advocate for, there is a need for better information. Differences in the responses to the questions "how and when to screen" shows that the screening path depends on the disease and the presence of a disease modifying treatment. The unmet need for screening inherited NMDs should follow an adaptive pathway related to the fast moving medical landscape of NMDs. International coordination leading to a common policy would certainly be a precious asset tending to harmonize the situation amongst European countries.

The physical demands of daily life in developed countries have decreased remarkably during the last two centuries. General leisure time has increased and the age at retirement has decreased. General health has improved and life expectancy has increased. Most people can expect to live 20-30 years after retirement. By 2050, one in four people in Europe and North America will be aged 65 or over. Furthermore, women live longer than men. Generally, the physical demands on older women will be low. Thus, their physical fitness will decline, which in turn will affect a variety of organ systems and functions, and so impact on mental health, quality of life and independent living. This opinion paper explores exercise strategies for healthy ageing., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Management of decompensated cirrhosis is currently geared towards the treatment of complications once they occur. To date there is no established disease-modifying therapy aimed at halting progression of the disease and preventing the development of complications in patients with decompensated cirrhosis. The design of clinical trials to investigate new therapies for patients with decompensated cirrhosis is complex. The population of patients with decompensated cirrhosis is heterogeneous (i.e., different etiologies, comorbidities and disease severity), leading to the inclusion of diverse populations in clinical trials. In addition, primary endpoints selected for trials that include patients with decompensated cirrhosis are not homogeneous and at times may not be appropriate. This leads to difficulties in comparing results obtained from different trials. Against this background, the LiverHope Consortium organized a meeting of experts, the goal of which was to develop recommendations for the design of clinical trials and to define appropriate endpoints, both for trials aimed at modifying the natural history and preventing progression of decompensated cirrhosis, as well as for trials aimed at managing the individual complications of cirrhosis., Competing Interests: Conflict of interest ES, CA, RH, EP, SM, CF, RM have nothing to declare. The other authors declare the following: PG has participated on advisory boards for the following: Grifols, Gilead, Intercept, Mallinckrodt and Ferring. He has received Investigator promoted research grants from Mallinckrodt, Gilead and Grifols. All outside the submitted work. SM research group has received consultancy fees and/or research donations from Merz Pharmaceuticals GmbH, Norgine, Alfasigma and Umecrine Cognition. VV speaking fees from Intercept Pharmaceuticals; advisory board fees from Promethera Biosciences PC Grifols SA: advisory board, speaking bureau; Octapharma. SA: speaking bureau; Takeda SA: speaking bureau. JT: reports other from - Gore, Bayer, Alexion, MSD, Gilead, Intercept, Norgine, Grifols, Versantis, Martin Pharmaceuticals outside the submitted work. PSK is Principal Investigator of the Sequana Medical sponsored POSEIDON study in North America. He does not receive any personal remuneration. HW declares he is currently and employee of EVOTEC and has shares in Sanofi, both of which are unrelated to the work submitted. JGA reports grants from Gilead, lecture fees from Ferring, and consulting fees from Gilead, Pfizer, Intercept, Boehringer-Ingelheim, Lupin and Genfit outside the submitted work. UB Research funding from South African PSC Patient Foundation, Netherlands gastroenterology and hepatology (MDLS) Foundation, Investigator initiated research funding from Intercept, USA. AK Speaker and advisory board: Norgine, Siemens. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

The EC Directive 2013/59/Euratom states in article 56 that exposures of target volumes in nuclear medicine treatments shall be individually planned and their delivery appropriately verified. The Directive also mentions that medical physics experts should always be appropriately involved in those treatments. Although it is obvious that, in nuclear medicine practice, every nuclear medicine physician and physicist should follow national rules and legislation, the EANM considered it necessary to provide guidance on how to interpret the Directive statements for nuclear medicine treatments.For this purpose, the EANM proposes to distinguish three levels in compliance to the optimization principle in the directive, inspired by the indication of levels in prescribing, recording and reporting of absorbed doses after radiotherapy defined by the International Commission on Radiation Units and Measurements (ICRU): Most nuclear medicine treatments currently applied in Europe are standardized. The minimum requirement for those treatments is ICRU level 1 ("activity-based prescription and patient-averaged dosimetry"), which is defined by administering the activity within 10% of the intended activity, typically according to the package insert or to the respective EANM guidelines, followed by verification of the therapy delivery, if applicable. Non-standardized treatments are essentially those in developmental phase or approved radiopharmaceuticals being used off-label with significantly (> 25% more than in the label) higher activities. These treatments should comply with ICRU level 2 ("activity-based prescription and patient-specific dosimetry"), which implies recording and reporting of the absorbed dose to organs at risk and optionally the absorbed dose to treatment regions. The EANM strongly encourages to foster research that eventually leads to treatment planning according to ICRU level 3 ("dosimetry-guided patient-specific prescription and verification"), whenever possible and relevant. Evidence for superiority of therapy prescription on basis of patient-specific dosimetry has not been obtained. However, the authors believe that a better understanding of therapy dosimetry, i.e. how much and where the energy is delivered, and radiobiology, i.e. radiation-related processes in tissues, are keys to the long-term improvement of our treatments.

COVID-19 is also manifested with hypercoagulability, pulmonary intravascular coagulation, microangiopathy, and venous thromboembolism (VTE) or arterial thrombosis. Predisposing risk factors to severe COVID-19 are male sex, underlying cardiovascular disease, or cardiovascular risk factors including noncontrolled diabetes mellitus or arterial hypertension, obesity, and advanced age. The VAS-European Independent Foundation in Angiology/Vascular Medicine draws attention to patients with vascular disease (VD) and presents an integral strategy for the management of patients with VD or cardiovascular risk factors (VD-CVR) and COVID-19. VAS recommends (1) a COVID-19-oriented primary health care network for patients with VD-CVR for identification of patients with VD-CVR in the community and patients' education for disease symptoms, use of eHealth technology, adherence to the antithrombotic and vascular regulating treatments, and (2) close medical follow-up for efficacious control of VD progression and prompt application of physical and social distancing measures in case of new epidemic waves. For patients with VD-CVR who receive home treatment for COVID-19, VAS recommends assessment for (1) disease worsening risk and prioritized hospitalization of those at high risk and (2) VTE risk assessment and thromboprophylaxis with rivaroxaban, betrixaban, or low-molecular-weight heparin (LMWH) for those at high risk. For hospitalized patients with VD-CVR and COVID-19, VAS recommends (1) routine thromboprophylaxis with weight-adjusted intermediate doses of LMWH (unless contraindication); (2) LMWH as the drug of choice over unfractionated heparin or direct oral anticoagulants for the treatment of VTE or hypercoagulability; (3) careful evaluation of the risk for disease worsening and prompt application of targeted antiviral or convalescence treatments; (4) monitoring of D-dimer for optimization of the antithrombotic treatment; and (5) evaluation of the risk of VTE before hospital discharge using the IMPROVE-D-dimer score and prolonged post-discharge thromboprophylaxis with rivaroxaban, betrixaban, or LMWH., Competing Interests: None declared., (Thieme. All rights reserved.)

Since the introduction of allergen immunotherapy (AIT) over 100 years ago, focus has been on standardization of allergen extracts, with reliable molecular composition of allergens receiving the highest attention. While adjuvants play a major role in European AIT, they have been less well studied. In this Position Paper, we summarize current unmet needs of adjuvants in AIT citing current evidence. Four adjuvants are used in products marketed in Europe: aluminium hydroxide (Al(OH) 3 ) is the most frequently used adjuvant, with microcrystalline tyrosine (MCT), monophosphoryl lipid A (MPLA) and calcium phosphate (CaP) used less frequently. Recent studies on humans, and using mouse models, have characterized in part the mechanisms of action of adjuvants on pre-existing immune responses. AIT differs from prophylactic vaccines that provoke immunity to infectious agents, as in allergy the patient is presensitized to the antigen. The intended mode of action of adjuvants is to simultaneously enhance the immunogenicity of the allergen, while precipitating the allergen at the injection site to reduce the risk of anaphylaxis. Contrasting immune effects are seen with different adjuvants. Aluminium hydroxide initially boosts Th2 responses, while the other adjuvants utilized in AIT redirect the Th2 immune response towards Th1 immunity. After varying lengths of time, each of the adjuvants supports tolerance. Further studies of the mechanisms of action of adjuvants may advise shorter treatment periods than the current three-to-five-year regimens, enhancing patient adherence. Improved lead compounds from the adjuvant pipeline are under development and are explored for their capacity to fill this unmet need., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)