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Introduction: In adults with a suspicion of peripheral bone infection, evidence-based guidelines in choosing the most accurate diagnostic strategy are lacking., Aim and Methods: To provide an evidence-based, multidisciplinary consensus document on the diagnostic management of adult patients with PBIs, we performed a systematic review of relevant infectious, microbiological, orthopedic, radiological, and nuclear medicine literature. Delegates from four European societies (European Bone and Joint Infection Society, European Society of Microbiology and Infectious Diseases, European Society or Radiology, and European Association of Nuclear Medicine) defined clinical questions to be addressed, thoroughly reviewed the literature pertinent to each of the questions, and thereby evaluated the diagnostic accuracy of each diagnostic technique. Inclusion of the papers per statement was based on a PICO (Population/problem - Intervention/indicator - Comparator - Outcome) question following the strategy reported by the Oxford Centre for Evidence-based Medicine. For each statement, the level of evidence was graded according to the 2011 review of the Oxford Centre for Evidence-based Medicine. All approved statements were addressed taking into consideration the available diagnostic procedures, patient acceptance, tolerability, complications, and costs in Europe. Finally, a commonly agreed-upon diagnostic flowchart was developed.

Case management is generally seen as a way to provide efficient, cost-saving person-centred care for people with dementia by connecting together fragmented services, but the available evidence in favour of its merits is often considered inconclusive, unclear and sketchy. This discussion paper investigates the evidence of the benefit of case management for people with dementia and explores the complexity of the concept and the experiences of its implementation. It offers a comprehensive framework for conceptualising various types of case management and asks the question: who can be a case manager? Building on examples from three European countries it addresses the problem of the expansion and adoption of the case management method. It compares the conventional model of diffusion of innovation with the ideas of interessement and co-constitution and envisions a successful model of case management as a fluid technology that is both friendly and flexible, allowing it to adapt to different settings and systems.

An interdisciplinary task force of European experts summarizes the value of gastrointestinal ultrasound (GIUS) in the management of acute appendicitis and diverticulitis. Based on an extensive literature review, clinical recommendations for these highly common diseases in visceral medicine are presented.In patients with acute appendicitis, preoperative sonography has been established as a routine procedure in most European countries for medical and legal reasons. Routine sonography in these patients may reduce the rate of unnecessary surgery by half. The sensitivity, specificity, and accuracy of ultrasound reach values above 90 % and are equivalent to CT and MRI. However, the high operator dependence may be a problem, for example in point-of-care ultrasound in emergency departments. Structured training programs, quality controls and standardized ultrasound reporting should be increasingly implemented.In the case of suspected acute diverticulitis, "ultrasound first" should also be a basic element in the approach to all patients. Sonography can confirm the diagnosis and allows early risk stratification. As treatment strategies have become less aggressive and more tailored to the stage of diverticulitis, accurate staging has become increasingly important. GIUS and CT have proven to have similar sensitivity and specificity. Especially in cases of uncomplicated diverticulitis, GIUS will be the one and only imaging procedure. CT may work as a backup and has particular advantages for diverticulitis located in the distal sigmoid, inflammation deep in the small pelvis and insufficient ultrasound scanning conditions. This step-up approach (ultrasound first and CT only in case of a negative or inconclusive ultrasound result) has proven to yield the best accuracy., Competing Interests: Speaker honoraria, Pentax Medical Singapore LtdConsulting/Advisory board, Mediglobe Corporation GmbhCongress participation support, Hitachi Medical Systems UKSpeaker honoraria, Abbvie, Janssen, TakedaSpeaker honoraria, Bracco, Hitachi, GE, Mindray, Supersonic, Pentax, Olympus, Fuji,Boston Scientific, AbbVie, Falk Foundation, Novartis, Roche; AdvisoryBoard Member, Hitachi, Mindray, Siemens; Research grant, GEMindray, SuperSonicSpeaker honoraria, AbbVie, Bracco, Almirall, GE Healthcare, Takeda AS, Meda AS, Ferring AS, AllegaConsultant fee Bracco, GE Healthcare, Takeda and SamsungSpeaker honoraria, Abbvie, Falk Foundation, Ferring, Janssen-Cilag, MSD, Pfizer, Takeda;Advisory Board/Consultant fee: Abbvie, Celgene, Janssen-Cilag, MSD, TakedaSpeaker honoraria, Abbvie, Alfa Sigma, Janssen-Cilag; Advisory Board/Consultant fee, Allergan, Novartis, Takeda, THDSpeaker honoraria, Falk Foundation; Research grant, GE HealthcareSpeaker honoraria, Meda AS, Ferring pharmaceuticals, TakedaSpeaker honoraria, Philips, GE, Canon; Advisory Board Member, Siemens; Congress participation support, SiemensSpeaker honoraria Bracco, Toshiba. Advisory board member Bracco. Education support Philips. Technical consultancy Philips, BK The following members declared no conflicts of interest: Klaus Dirks, Trygve Hausken, Antony Higginson, Alois Holleweger, Nadia Palotta, Tomás Ripollés, Laura Romanini, Carla Serra, (© Georg Thieme Verlag KG Stuttgart · New York.)

Background and Objective: Pain is a common symptom in patients who survive cancer and in those who live with progressive advanced disease. Evidence from meta-analyses suggests that pain remains poorly controlled for a large proportion of patients; barriers to good management include poor assessment of pain, inadequate support for patient self-management and late or inadequate access to strong opioid analgesia in those with advanced disease., Methods: The European Pain Federation (EFIC) established a Task Force in 2017 which convened a European group of experts, drawn from a diverse range of relevant clinical disciplines, to prepare a position paper on appropriate standards for the management of cancer-related pain. The expert panel reviewed the available literature and made recommendations using the GRADE system to combine quality of evidence with strength of recommendation. The panel took into account the desirable and undesirable effects of the management recommendation, including the cost and inconvenience of each when deciding the recommendation., Results and Conclusions: The 10 standards presented are aimed to improve cancer pain management and reduce variation in practice across Europe. The Task Force believes that adoption of these standards by all 37 countries will promote the quality of care of patients with cancer-related pain and reduce unnecessary suffering., Significance: Pain affects up to 40% of cancer survivors and affects at least 66% of patients with advanced progressive disease, many of whom experience poor pain control. These 10 standards are aimed to improve cancer pain management, promote the quality of care of patients and reduce variation across Europe., (© 2018 European Pain Federation - EFIC®.)

Subgroup by treatment interaction assessments are routinely performed when analysing clinical trials and are particularly important for phase 3 trials where the results may affect regulatory labelling. Interpretation of such interactions is particularly difficult, as on one hand the subgroup finding can be due to chance, but equally such analyses are known to have a low chance of detecting differential treatment effects across subgroup levels, so may overlook important differences in therapeutic efficacy. EMA have therefore issued draft guidance on the use of subgroup analyses in this setting. Although this guidance provided clear proposals on the importance of pre-specification of likely subgroup effects and how to use this when interpreting trial results, it is less clear which analysis methods would be reasonable, and how to interpret apparent subgroup effects in terms of whether further evaluation or action is necessary. A PSI/EFSPI Working Group has therefore been investigating a focused set of analysis approaches to assess treatment effect heterogeneity across subgroups in confirmatory clinical trials that take account of the number of subgroups explored and also investigating the ability of each method to detect such subgroup heterogeneity. This evaluation has shown that the plotting of standardised effects, bias-adjusted bootstrapping method and SIDES method all perform more favourably than traditional approaches such as investigating all subgroup-by-treatment interactions individually or applying a global test of interaction. Therefore, these approaches should be considered to aid interpretation and provide context for observed results from subgroup analyses conducted for phase 3 clinical trials., (© 2018 John Wiley & Sons, Ltd.)

Purpose: Major trauma remains a significant cause of morbidity and mortality in the developed and developing world. In 2013, nearly 5 million people worldwide died from their injuries, and almost 1 billion individuals sustained injuries that warranted some type of healthcare, accounting for around 10% of the global burden of disease in general. Behind the statistics, severe trauma takes a major toll on individuals, their families and healthcare systems. Management of the patient with severe trauma requires multiple interventions in a highly time-sensitive context and fragmentation of care, characterised by loss of information and time among disciplines, departments and individuals, both outside the hospital and within it, is frequent. Outcomes may be improved by better streamlining of pre- and intra-hospital care., Methods: We describe the basis for development of a multi-stakeholder consortium by the European Critical Care Foundation working closely with a number of European Scientific Societies to address and overcome problems of fragmentation in the care of patients with severe trauma., Result: The consortium will develop and introduce an information management system adapted to severe trauma, which will integrate continuous monitoring of vital parameters and point-of-care diagnostics. The key innovation of the project is to harness the power of information technologies and artificial intelligence to provide computer-enhanced clinical evaluation and decision-support to streamline the multiple points at which information and time are potentially lost., Conclusions: The severe trauma management platform thus created could have multiple benefits beyond its immediate use in managing the care of injured patients.

Exercise training (ET) and secondary prevention measures in cardiovascular disease aim to stimulate early physical activity and to facilitate recovery and improve health behaviours. ET has also been proposed for heart failure patients with a ventricular assist device (VAD), to help recovery in the patient's functional capacity. However, the existing evidence in support of ET in these patients remains limited. After a review of current knowledge on the causes of the persistence of limitation in exercise capacity in VAD recipients, and concerning the benefit of ET in VAD patients, the Heart Failure Association of the European Society of Cardiology has developed the present document to provide practical advice on implementing ET. This includes appropriate screening to avoid complications and then starting with early mobilisation, ET prescription is individualised to meet the patient's needs. Finally, gaps in our knowledge are discussed., (© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.)

Background: Health risks associated with the high consumption of sugar-sweetened beverages (SSBs) include overweight or obesity and their complications such as diabetes, as well as oral and dental decay, among others., Aim: The aim of the present statement is to inform health care professionals, parents, care-givers, teachers and school head teachers, stakeholders and governing bodies about the risks associated with drinking SSBs in infants, children and adolescents., Methods: We searched PubMed and the Cochrane databases for English language studies published from 2010 through October 1, 2018, for randomized clinical trials, meta-analyses, systematic reviews and observational studies (search terms are reported in eAppendix in the Supplement). We also manually searched the references of selected articles, reviews, meta-analyses and practice guidelines., Recommendations: Consumption of SSB by children and adolescents should be limited, and the consumption of water and other non-sweetened beverages should be promoted. Educational institutions such as nurseries, pre-schools and schools should offer unlimited access to drinking water, whereas the sale of SSBs should be banned., (© 2019 S. Karger AG, Basel.)

Fecal microbiota transplantation (FMT) is becoming part of the treatment algorithms against recurrent Clostridium difficile infection (rCDI) both in adult and pediatric gastroenterology practice. With our increasing recognition of the critical role the microbiome plays in human health and disease, FMT is also being considered as a potential therapy for other disorders, including inflammatory bowel disease (Crohn disease, ulcerative colitis), graft versus host disease, neuropsychiatric diseases, and metabolic syndrome. Controlled trials with FMT for rCDI have not been performed in children, and numerous clinical and regulatory considerations have to be considered when using this untraditional therapy. This report is intended to provide guidance for FMT in the treatment of rCDI in pediatric patients.

The current study aimed to identify and analyze the 100 most cited papers on the topic of nutraceuticals and functional foods. Scopus database was searched to extract bibliometric data. Two-thirds of the 100 most cited papers were reviews. Papers were mostly published in food science and nutrition journals, and one-third were published in seven journals, namely: British Journal of Nutrition (6), Critical Reviews in Food Science and Nutrition (6), Journal of Food Science (5), Trends in Food Science and Technology (5), American Journal of Clinical Nutrition (4), Food Chemistry (4) and Journal of Nutrition (4). Topics with high citation counts dealt with prebiotics, probiotics, antioxidants and phenolic content. Hot topics with over 1000 citations per paper include bifidobacterium (1147), colon (1032) and lipid metabolism (1013). The United States and Europe were major places of origin. These results can serve as a quick benchmarking reference for researchers or general public members., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Over the last 70 years, pharmacotherapy in gout with urate-lowering drugs has consisted of four drugs only: In 1952, a mild uricosuric probenecid became available, the xanthine oxidase inhibitor Allopurinol in 1964, and the latter became the most frequently used urate-lowering drug worldwide; in the Eurozone, the uricosuric benzbromarone was welcomed in 1977. Only in 2002, the potent non-purine xanthine oxidase inhibitor febuxostat was introduced. In many countries, uricosurics such as probenecid and benzbromarone have not been available up to now, and these days, the new uricosuric lesinurad is the first uricosuric that may be introduced in these countries, which is the reason for describing the position this novel uricosuric deserves in treating gout. Recent literature will be shortly reviewed, and the current proposed position for lesinurad will be given as an aid for clinicians.

We recommend that intestinal failure associated liver disease (IFALD) should be diagnosed by the presence of abnormal liver function tests and/or evidence of radiological and/or histological liver abnormalities occurring in an individual with IF, in the absence of another primary parenchymal liver pathology (e.g. viral or autoimmune hepatitis), other hepatotoxic factors (e.g. alcohol/medication) or biliary obstruction. The presence or absence of sepsis should be noted, along with the duration of PN administration. Abnormal liver histology is not mandatory for a diagnosis of IFALD and the decision to perform a liver biopsy should be made on a case-by-case basis, but should be particularly considered in those with a persistent abnormal conjugated bilirubin in the absence of intra or extra-hepatic cholestasis on radiological imaging and/or persistent or worsening hyperbilirubinaemia despite resolution of any underlying sepsis and/or any clinical or radiological features of chronic liver disease. Nutritional approaches aimed at minimising PN overfeeding and optimising oral/enteral nutrition should be instituted to prevent and/or manage IFALD. We further recommend that the lipid administered is limited to less than 1 g/kg/day, and the prescribed omega-6/omega-3 PUFA ratio is reduced wherever possible. For patients with any evidence of progressive hepatic fibrosis or overt liver failure, combined intestinal and liver transplantation should be considered., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: The first edition of the European position paper (EPP) on drug-induced sleep endoscopy (DISE) was published in 2014 with the aim to standardise the procedure, to provide an in-depth insight into the main aspects of this technique and to have a basis for future research. Since 2014, new studies have been published concerning new sedative agents or new insights into the pattern/levels of the obstruction depending on the depth of sedation. Therefore, an enlarged group of European experts in the field of sleep breathing disorders (SBD), including the most of the first DISE EPP main authors, has decided to publish an update of the European position paper on DISE, in order to include new evidence and to find a common language useful for reporting the findings of this endoscopic evaluation in adult population affected by SBD., Methods: The authors have evaluated all the available evidence reported in the literature and have compared experience among various departments in leading European centres in order to provide an update regarding the standardisation of the DISE procedure and an in-depth insight into the main aspects of this technique., Results: After the first European Position Consensus Meeting on DISE and its update, consensus was confirmed for indications, required preliminary examinations, where to perform DISE, technical equipment required, staffing, local anaesthesia, nasal decongestion, other medications, patient positioning, basics and special diagnostic manoeuvres, drugs and observation windows. So far, no consensus could be reached on a scoring and classification system. However, regarding this aim, the idea of an essential classification, such as VOTE with the possibility of its graded implementation of information and descriptions, seems to be the best way to reach a universal consensus on DISE classification at this stage. A common DISE language is mandatory, and attempts to come to a generally accepted system should be pursued., (© 2018 John Wiley & Sons Ltd.)

The population of patients with congenital heart disease (CHD) is continuously increasing with more and more patients reaching adulthood. A significant portion of these young adults will suffer from arrhythmias due to the underlying congenital heart defect itself or as a sequela of interventional or surgical treatment. The medical community will encounter an increasing challenge as even most of the individuals with complex congenital heart defects nowadays become young adults. Within the past 20 years, management of patients with arrhythmias has gained remarkable progress including pharmacological treatment, catheter ablation, and device therapy. Catheter ablation in patients with CHD has paralleled the advances of this technology in pediatric and adult patients with structurally normal hearts. Growing experience and introduction of new techniques like the 3D mapping systems into clinical practice have been particularly beneficial for this growing population of patients with abnormal cardiac anatomy and physiology. Finally, device therapies allowing maintanence of chronotropic competence and AV conduction, improving haemodynamics by cardiac resynchronization, and preventing sudden death are increasingly used. For pharmacological therapy, ablation procedures, and device therapy decision making requires a deep understanding of the individual pathological anatomy and physiology as well as detailed knowledge on natural history and long-term prognosis of our patients. Composing expert opinions from cardiology and paediatric cardiology as well as from non-invasive and invasive electrophysiology this position paper was designed to state the art in management of young individuals with congenital heart defects and arrhythmias.

The European Academy of Cancer Sciences (EACS) is an independent advisory body of well-recognised medical specialists and researchers striving to create a compelling interactive continuum of cancer research, from innovative basic research to implementation of state-of-the-art evidence-based cancer care and prevention. Achieving the above will entail bridging high-quality basic and preclinical cancer research to research on prevention, early detection and therapeutics as well as improving coordination of translational research efforts across Europe. The latter is expected to be expedited through quality assuring translational cancer research in Comprehensive Cancer Centres - entities that link research with the healthcare system - and networks of cancer research centres. Achieving a critical mass of expertise, resources and patients is crucial. Improving late translational research, which involves clinical studies to assess effectiveness, and added value for the health care is also a high priority. Both high-quality Big Data collections and the intelligent use of these data will promote innovation in cancer research and support outcomes research to assess clinical utility, quality of cancer care and long-term follow-up of treated patients. The EACS supports the mission-oriented approach recently proposed by the European Commission in Horizon Europe to deal with major challenges and would like to persuade the EU and its member states to formally launch a mission in cancer to boost and streamline the cancer research continuum in Europe. Building a coherent translational cancer research continuum with a focus on patients and individuals at risk will require, however, foresight as well as the extensive and continuous provision of evidence-based advice to inform policy., (© 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

Background: Since there is sound evidence that communication skills training (CST) programs modify communication behavior of oncology clinicians, they have been widely implemented over the last decades. However, more recently, certain aspects of this training have been criticized., Methods: Based on this background, a call to re-launch a discussion about the future of CST led to the third European consensus meeting on communication in cancer care, organized by the Swiss Cancer League. During this meeting, which brought together European experts in the field of clinical communication and training of communication in the oncology setting, oncology clinicians, representatives of the European Society of Medical Oncology and a member of the European Oncology Nursing Society, the recommendations of the second European consensus meeting were updated and expanded., Results: The expanded recommendations recall the guiding principles of communication in cancer care, underline the important role of clinician's self-awareness, and of relational and contextual factors in clinical communication, and provide direction for the further development of communication training., Conclusion: This third European consensus meeting defines key elements for the development of a next generation of communication training for oncology clinicians.

: This ESH update was deemed necessary with the publication of new results of sham-controlled randomized blinded prospective trials with renal denervation (RDN). Proof of concept studies and first randomized trials (some were sham-controlled) displayed discrepant results about the efficacy of RDN. Three sham-controlled randomized trials of the 2.0 generation yielded now similarity in the average blood pressure decrease following RDN. Reduction of ambulatory blood pressure was approximately 5 to 7 mmHg and of office blood pressure 10 mmHg. Such a decrease in blood pressure by pharmacologic therapy has been found to be associated with lower incidence of cardiovascular events in particular with respect to heart failure and stroke by roughly 25%. Nevertheless, some questions about renal denervation are unanswered. The heterogeneity of the blood pressure-lowering response point to the clinical need to identify predictors for efficacy, and questions on long-term safety could not have been answered due to the short duration of the sham-controlled randomized clinical trials.

Cannabis-based medicines are being approved for pain management in an increasing number of European countries. There are uncertainties and controversies on the role and appropriate use of cannabis-based medicines for the management of chronic pain. EFIC convened a European group of experts, drawn from a diverse range of basic science and relevant clinical disciplines, to prepare a position paper to empower and inform specialist and nonspecialist prescribers on appropriate use of cannabis-based medicines for chronic pain. The expert panel reviewed the available literature and harnessed the clinical experience to produce these series of recommendations. Therapy with cannabis-based medicines should only be considered by experienced clinicians as part of a multidisciplinary treatment and preferably as adjunctive medication if guideline-recommended first- and second-line therapies have not provided sufficient efficacy or tolerability. The quantity and quality of evidence are such that cannabis-based medicines may be reasonably considered for chronic neuropathic pain. For all other chronic pain conditions (cancer, non-neuropathic noncancer pain), the use of cannabis-based medicines should be regarded as an individual therapeutic trial. Realistic goals of therapy have to be defined. All patients must be kept under close clinical surveillance. As with any other medical therapy, if the treatment fails to reach the predefined goals and/or the patient is additionally burdened by an unacceptable level of adverse effects and/or there are signs of abuse and misuse of the drug by the patient, therapy with cannabis-based medicines should be terminated., Significance: This position paper provides expert recommendations for nonspecialist and specialist healthcare professionals in Europe, on the importance and the appropriate use of cannabis-based medicines as part of a multidisciplinary approach to pain management, in properly selected and supervised patients., (© 2018 European Pain Federation - EFIC®.)

In endocrine diseases, hormonal changes, electrolyte abnormalities, and the deterioration of heart structure can lead to various arrhythmias. In diabetic patients, hypoglycemia, hyperglycemia, and hypokalemia can trigger arrhythmias, and diabetic cardiomyopathy can also cause electrical and structural remodeling to form substrates for arrhythmias. The risk of atrial fibrillation (AF) increases in hyperthyroidism; however, the prevalence of ventricular arrhythmias in hypothyroidism is higher. Besides AF and ventricular tachycardias, bradycardias and atrioventricular blocks can also be seen in pheochromocytoma due to the desensitization of adrenergic cardiovascular receptors. The correction of metabolic and electrolyte disturbances in patients with adrenal cortex disease should be the main approach in the prevention and treatment of arrhythmias. Early initiation of treatment in patients with acromegaly seems to decrease the development of cardiac remodeling and ventricular arrhythmia. Early and late after depolarizations due to hypercalcemia in hyperparathyroidism can lead to life-threatening ventricular arrhythmias. This elegant position paper provides important recommendations regarding prevention and treatment of arrhythmias for specific endocrine disorders.

Background: The European & Developing Countries Clinical Trials Partnership (EDCTP), like many other research funders, requires its grantees to make papers available via open access (OA). This article investigates the effect of publishing in OA journals and international collaboration within and between European and sub-Saharan African countries on citation impact and likelihood of falling into the top 1% and top 10% most cited papers in poverty-related disease (PRD) research., Methods: Disease-specific research publications were identified in the Web of Science™ and MEDLINE using Medical Subject Heading (MeSH) terms. Data on the open accessibility of scientific literature were derived from 1science oaFindr. Publication data, including relative citation counts, were extracted for 2003-2015. Regression models were applied to quantify the relationship between relative citations and presence in the 1% and top 10% most cited papers versus OA and international collaboration., Results: The results show that since 2003 papers on PRDs have become increasingly available in OA. Among all PRD areas, malaria research is most frequently published in OA and in international collaboration. The adjusted regression analyses show that holding other factors constant, publishing research in OA and in international collaboration has a significant and meaningful citation advantage over non-OA or non-international collaborative research. Publishing papers as part of a European-wide or European- sub-Saharan African collaboration increases research impact. In contrast, such collaboration advantage is not observed for research output involving sub-Saharan Africa only which seems to decrease research impact., Conclusions: Our results indicate that there is a real, measurable citation advantage for publishing PRD research in OA and international collaboration. However, the international collaboration advantage seems to be region-specific with increased research impact for European-wide and European-sub-Saharan African collaborations but a decrease in research impact of collaborations confined to sub-Saharan African research institutions. Further research is required to further verify this finding and to understand the underlying factors related to this observed decrease in research impact. To target future research capacity building activities in sub-Saharan Africa it is important to assess whether the observed decreased impact reflects the scientific competencies and geographic distribution of individual researchers or institutional-, national- or funder-specific research requirements., Competing Interests: JGB and MMM have no competing interests to declare. CT, GR, MD and DBS have the following interests to declare: CT, GR, MD and DBS are employed by Science-Metrix. Financial support was provided by Science-Metrix for the manuscript preparation (over and above the contracted study) in the form of salaries for CT, GR, MD and DBS. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Endoscopy is a central tool for the evaluation and management of inflammatory bowel disease (IBD). In the last few decades, gastrointestinal (GI) endoscopy has undergone significant technological developments including availability of pediatric-size equipment, enabling comprehensive investigation of the GI tract in children. Simultaneously, professional organization of GI experts have developed guidelines and training programs in pediatric GI endoscopy. This prompted the Porto Group on Pediatric IBD of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition to develop updated guidelines on the role of GI endoscopy in pediatric IBD, specifically taking into considerations of recent advances in the diagnosis, disease stratification, and novel therapeutic targets in these patients.

This paper reviews the current epidemiological data on peripheral artery disease (PAD) in Europe. Cardiovascular disease (CVD) burden is presented and PAD prevalence is discussed, as compared to coronary (CAD) and cerebrovascular (CeVD) diseases, in European Union (EU) countries and European continent countries. The article reviews PAD clinical manifestations, PAD diagnosis, risk factors for PAD incidence and progression, PAD prognosis and financial implications. CVD mortality is higher in women than in men and in European continent countries, as compared to EU countries. While CAD and CeVD have a lower prevalence in EU countries, as compared to the whole continent, PAD and other CVDs still have a higher prevalence in EU countries. PAD prevalence vary widely between countries, increases sharply with aging and has a relation with ethnicity. CVD comorbidities are high in PAD subjects and particularly high in those with critical limb ischemia. PAD prognosis is related to CAD and CeVD mortality, that are particularly high in critical limb ischemia. This review promotes the need for global awareness on PAD burden, stimulates PAD screening and emphasizes the importance of early diagnosis and treatment of PAD and associated cardiovascular comorbidities.

: Whether isolated systolic hypertension in the young (ISHY) implies a worse outcome and needs antihypertensive treatment is still a matter for dispute. ISHY is thought to have different mechanisms than systolic hypertension in the elderly. However, findings from previous studies have provided inconsistent results. From the analysis of the literature, two main lines of research and conceptualization have emerged. Simultaneous assessment of peripheral and central blood pressure led to the identification of a condition called pseudo or spurious hypertension, which was considered an innocent condition. However, an increase in pulse wave velocity has been found by some authors in about 20% of the individuals with ISHY. In addition, obesity and metabolic disturbances have often been documented to be associated with ISHY both in children and young adults. The first aspect to consider whenever evaluating a person with ISHY is the possible presence of white-coat hypertension, which has been frequently found in this condition. In addition, assessment of central blood pressure is useful for identifying ISHY patients whose central blood pressure is normal. ISHY is infrequently mentioned in the guidelines on diagnosis and treatment of hypertension. According to the 2013 European Guidelines on the management of hypertension, people with ISHY should be followed carefully, modifying risk factors by lifestyle changes and avoiding antihypertensive drugs. Only future clinical trials will elucidate if a benefit can be achieved with pharmacological treatment in some subgroups of ISHY patients with associated risk factors and/or high central blood pressure.

Peripartum cardiomyopathy is an idiopathic cardiomyopathy presenting with heart failure secondary to left ventricular systolic dysfunction towards the end of pregnancy or in the months following delivery, where no other cause for heart failure is identified. Outcome varies from full recovery to residual left ventricular systolic dysfunction and even death. Many women return to their physician to acquire information on their long-term prognosis, to seek medical advice regarding contraception, or when planning a subsequent pregnancy. This position paper summarizes current evidence for long-term outcome, risk stratification of further pregnancies and overall management. Based on the best available evidence, as well as the clinical experience of the European Society of Cardiology Study Group on Peripartum Cardiomyopathy members, a consensus on pre- and postpartum management algorithms for women undergoing a subsequent pregnancy is presented., (© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.)

Purpose: In recent years, evidence has emerged about the importance of healthy fluid intake in children for physical and mental performance and health, and in the prevention of obesity. Accurate data on water intake are needed to inform researchers and policymakers and for setting dietary reference values. However, to date, there are few published data on fluid or water intakes in children. This is due partly to the fact that drinking water is not always reported in dietary surveys. The aim of this paper is to review the current status of the literature and highlight the challenges of assessing total fluid intake in children and adolescents., Results: From the dietary assessment literature it is apparent that children present unique challenges to assessing intake due to ongoing cognitive capacity development, limited literacy skills, difficulties in estimating portion sizes and multiple caregivers during any 1 day making it difficult to track intakes. As such, many issues should be considered when assessing total fluid intakes in children or adolescents. Various methods to assess fluid intakes exist, each with its own strengths and weaknesses; the ultimate choice of method depends on the research question and resources available. Based on the literature review, it is apparent that if the research focus is to assess only fluid intake, a fluid-specific method, such as a diary or record, appears to be a feasible approach to provide an accurate estimate of intakes.

Papers used for food packing were studied for formaldehyde migration from them by the colorimetric method with acetylacetone. The studied material comprised 14 samples of paper of Polish or foreign production: pergamenous paper, offset and sulphite papers and one sample from waste paper imported from Germany. Formaldehyde migration from these samples differed but never exceeded 1 mg/dm2, with the exception of the recycled paper from which it was 1.77 mg/dm2.

In the past 20 years, there have been numerous reports of skin and mucous membrane disorders allegedly caused by the use of carbonless copy paper, to such an extent that some people in Europe were refusing to work with it and concern was expressed in the European Parliament. In view of its undoubted convenience and superiority over carbon paper, the author was asked by the Commission of the European Communities for a report. Based on visits to manufacturers and users and the investigation of complaints, the conclusion is that, as exposure to the constituents of the paper during its manufacture is considerably greater than in its use and no cases have arisen in his experience in the industry, the complaints are more likely to be attributable to "sick building syndrome" than to the specific effect of any component of the paper.

Background and Aims: A growing body of evidence supports the need for detailed attention to nutrition and diet in children with inflammatory bowel disease (IBD). We aimed to define the steps in instituting dietary or nutritional management in light of the current evidence and to offer a useful and practical guide to physicians and dieticians involved in the care of pediatric IBD patients., Methods: A group of 20 experts in pediatric IBD participated in an iterative consensus process including 2 face-to-face meetings, following an open call to Nutrition Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition Porto, IBD Interest, and Nutrition Committee. A list of 41 predefined questions was addressed by working subgroups based on a systematic review of the literature., Results: A total of 53 formal recommendations and 47 practice points were endorsed with a consensus rate of at least 80% on the following topics: nutritional assessment; macronutrients needs; trace elements, minerals, and vitamins; nutrition as a primary therapy of pediatric IBD; probiotics and prebiotics; specific dietary restrictions; and dietary compounds and the risk of IBD., Conclusions: This position paper represents a useful guide to help the clinicians in the management of nutrition issues in children with IBD.

Introduction: The WHO world health statistics report in 2015 shows that in Europe the overall obesity rate among adults is 21.5% in males and 24.5% in females. Obesity has important consequences for morbidity, disability and quality of life. The aim of the paper was to improve physical and rehabilitation medicine physicians' professional practice for the rehabilitation of patients with obesity and related comorbidities., Evidence Acquisition: A systematic review of the literature and a Consensus procedure by means of a Delphi method process has been performed involving the delegates of all European countries represented in the UEMS PRM Section., Evidence Synthesis: The systematic literature review is reported together with the 13 recommendations from the Delphi procedure., Conclusions: The professional role of PRM physicians in obesity is to propose a complete PRM treatment for the patients considering the comorbidities, impairments, activity limitations and participation restrictions, providing medical care and leadership to the multidisciplinary team, coordinating the individual PRM project developed in team in agreement with the patient and his family/care givers.

This paper discusses the relationship between environmental and economic performance and the influence of corporate strategies with regard to sustainability and the environment. After formulating a theoretical model, results are reported from an empirical analysis of the European paper manufacturing industry. New data are used to test hypotheses derived from the theoretical model, using environmental performance indices representing different corporate environmental strategy orientations. In particular, an emissions-based index largely reflecting end-of-pipe strategies and an inputs-based index reflecting integrated pollution prevention are distinguished. For the emissions-based index, a predominantly negative relationship between environmental and economic performance is found, whereas for the inputs-based index no significant link is found. This is consistent with the theoretical model, which predicts the possibility of different relationships. The results also show that for firms with pollution prevention-oriented corporate environmental strategies, the relationship between environmental and economic performance is more positive, thus making improvements in corporate sustainability more likely. Based on this last insight, managerial implications of this are discussed with regard to strategy choices, investment decisions and operations management.

Introduction: Acute kidney injury is associated with high mortality in the perioperative period of liver transplantation. The aim of this position paper was to provide an up-to-date overview with special emphases on diagnosis, risk factors, and treatment., Evidence Acquisition: The Liver Intensive Care Group of Europe nominated a panel of recognized international experts who reviewed the available literature published from 1990 to January 2016 and produced clinical recommendations. The level of evidence and strength of recommendation were judged according to the Grading of Recommendations Assessment Development and Evaluation system., Evidence Synthesis: Diagnosis of AKI should be based on the KDIGO criteria. The preoperative risk factors are more related to the patient's predisposing factors and post-operative risk factors tend to be difficult to control. Therefore, focusing on intra-operative risk factors it would be important to maintain an adequate hemodynamics and to keep inferior vena cava clamping as short as possible. Biomarkers to identify AKI at an early stage are available; however, there is a lack of robust data that indicates their true beneficial effect. Intraoperative renal replacement therapy may be beneficial in some selective cases whereas its postoperative timing is still under debate., Conclusions: Perioperative liver transplant risk factors for acute kidney injury are difficult to control. Therefore, the focus should be on intra-operative hemodynamics and nephrotoxic drugs avoidance. Prospective randomized trials are needed to show the beneficial effect of early replacement therapy. In this context, the new biomarkers would be helpful in identifying kidney injury earlier.

Recycled paperboard contains hundreds of non-evaluated or even unidentified substances that could endanger human health if they turn out to be highly toxic. It seems as unrealistic to evaluate each of them as it is to phase out the use of the problematic ones or sort out the papers and boards introducing them into the recyclate. Therefore, measures should be taken that generally reduce migration into food, such as functional barriers or functional sorbents. A general approach is used for the recycling of plastics, particularly poly(ethylene terephthalate), PET: as not every potential contaminant can be regulated, a pragmatic approach is applied, for PET mainly on the required decontamination efficiency. Criteria are required on the required efficacy of the measures to be taken. Recycled paperboard is used for various types of food contact: mostly contact is through the gas phase (evaporation and recondensation), often indirect through other layers (e.g. internal bags or for transport boxes), seldom in wetting contact. Numerous factors have to be considered. For typical folding boxes and at least strongly dominating gas phase contact, it was proposed that no more than 1% of each contaminant in the recycled paperboard should enter the food. The efficiency of the measures required to comply with this criterion depends on the application. The three main measures are reviewed with regard to this criterion: (i) internal bags with an incorporated functional barrier (successfully used for some time), (ii) a barrier layer on the internal wall of the box (for which the design of the closures might be most critical) and (iii) functional sorbents added to the paperboard (for which the sorbent capacity is critical). For transport boxes, commonly of corrugated board (quantitatively the most important use of recycled paperboard in food contact), an adjusted or different criterion is needed.

Purpose: The Cervical Spine Research Society Europe (CSRS-E) actively promotes scientific activities, the annual meeting being the most evident of them. The publication rate of oral and poster presentations at the annual meeting could be a measure for the success of the promotional activities. The publication rates of abstracts presented at the annual European meetings of the CSRS are unknown. The quality of the abstracts presented at a conference is reflected by the publication rate. A high publication rate is usually interpreted as representative of high scientific value of the conference., Methods: Poster and podium presentations from the 2007 to 2012 annual meetings were identified. Pubmed was used to search for the abstract title and/or the combination of authors to verify whether the data were published in a peer-reviewed journal. Abstracts were considered published if the data presented at the meeting were identical to that in the publication. The journals in which the data were published were identified, as well as the origin of the research centre., Results: From 2007 to 2012 826 abstracts were featured at the CSRS Europe annual meetings. There were 236 podium presentations and 590 poster presentations. 42 % of the podium presentations resulted in a publication, and 28 % of the poster presentations led to a publication. Overall, 32 % of accepted abstracts effectuated a publication in a peer-reviewed scientific journal. Abstracts from European research groups had a publication rate of 29 % compared to 34 % for abstracts from non-European research groups. Spine, European Spine Journal, Journal of Spinal Disorders and Techniques and J Neurosurgery Spine were the most common publication journals for the abstracts. The mean impact factor of the journals in which was published was 2.2., Conclusion: 42 % of the abstracts that were accepted for podium presentation at the CSRS Europe resulted in a publication in peer-reviewed MEDLINE indexed journals. Publication rates are at the high end of the publication rate spectrum of abstracts accepted for European scientific meetings.

In this work, a detailed technical-economic analysis of a fluidized bed based waste-to-energy system for disposal of paper manufacturing sludges has been carried out. Specific reference is made to a case study represented by the largest plant in Italy producing recycled paper, with a daily sludge output of about 52t. The adopted plant has been sized for a nominal capacity of 140t per day also allowing the progressive elimination of sludges accumulated in a previously utilized landfill, giving a nominal electrical power output of 3.5MW. The main plant sections have been described and the adopted technical solutions have been outlined. A detailed process and equipment characterization has been carried out leading to a thorough evaluation of capital investment, operating costs and revenues. A differential analysis has been performed with respect to the alternative solution represented by the disposal of untreated sludges in an external landfill in order to highlight the savings obtainable. The economic profitability of the investment has been evaluated regarding several performance indices. The economic evaluation has been completed by a sensitivity and risk analysis in order to assess the effects of uncertainties in the economically significant parameters. Adopting most probable values, the savings obtained with the considered waste-to-energy system are evaluated in the 15--20 million Euro range during the estimated plant life of 15 years with a foreseen pay back time of 4 years. Moreover, many environmental benefits result such as the remediation of existing landfill, the avoidance of new landfills opening and very low air pollutants emissions.

This article provides expert opinion on the use of cardiovascular magnetic resonance (CMR) in young patients with congenital heart disease (CHD) and in specific clinical situations. As peculiar challenges apply to imaging children, paediatric aspects are repeatedly discussed. The first section of the paper addresses settings and techniques, including the basic sequences used in paediatric CMR, safety, and sedation. In the second section, the indication, application, and clinical relevance of CMR in the most frequent CHD are discussed in detail. In the current era of multimodality imaging, the strengths of CMR are compared with other imaging modalities. At the end of each chapter, a brief summary with expert consensus key points is provided. The recommendations provided are strongly clinically oriented. The paper addresses not only imagers performing CMR, but also clinical cardiologists who want to know which information can be obtained by CMR and how to integrate it in clinical decision-making.

Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement., (© 2016 The authors.)

Performing well-designed and ethical trials in pediatric inflammatory bowel diseases (IBD) is a priority to support optimal therapy and reduce the unacceptable long lag between adult and pediatric drug approval. Recently, clinical trials in children have been incorporating placebo arms into their protocols under conditions that created controversy. Therefore, 4 organizations (the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition; European Crohn's and Colitis Organization; the Canadian Children IBD Network; and the Global Pediatric IBD Network) jointly provide a statement on the role of placebo in pediatric IBD trials. Consensus was achieved by 94 of 100 (94%) voting committees' members that placebo should only be used if there is genuine equipoise between the active treatment and placebo; for example, this may be considered in trials of drugs with new mechanisms of action without existing adult data, especially when proven effective alternatives do not exist outside the trial. Placebo may also be used in situations where it is an "add-on" to an effective therapy or to evaluate exit-strategies of maintenance therapy after long-term deep remission. It has been, however, agreed that no child enrolled in a trial should receive a known inferior treatment both within and outside the trial. This also includes withholding therapy in children who show clinical response after a short induction therapy. Given the similarity between pediatric and adult IBD regarding pathophysiology and response to treatments, drugs generally cannot be considered being in genuine equipoise with placebo if it has proven efficacy in adults. Continued collaboration of all stakeholders is needed to facilitate drug development and evaluation in pediatric IBD.

Background: Outcome measurement plays an increasing role in improving the quality, effectiveness, efficiency and availability of palliative care., Aim: To provide expert recommendations on outcome measurement in palliative care in clinical practice and research., Methods: Developed by a European Association for Palliative Care Task Force, based on literature searches, international expert workshop, development of outcome measurement guidance and international online survey. A subgroup drafted a first version and circulated it twice to the task force. The preliminary final version was circulated to wider expert panel and 28 international experts across 20 European Association for Palliative Care member associations and the European Association for Palliative Care Board of Directors and revised according to their feedback. The final version was approved by the European Association for Palliative Care Board for adoption as an official European Association for Palliative Care position paper., Results: In all, 12 recommendations are proposed covering key parameters of measures, adequate measures for the task, introduction of outcome measurement into practice, and national and international outcome comparisons and benchmarking. Compared to other recommendations, the White Paper covers similar aspects but focuses more on outcome measurement in clinical care and the wider policy impact of implementing outcome measurement in clinical palliative care. Patient-reported outcome measure feedback improves awareness of unmet need and allows professionals to act to address patients' needs. However, barriers and facilitators have been identified when implementing outcome measurement in clinical care that should be addressed., Conclusion: The White Paper recommends the introduction of outcome measurement into practice and outcomes that allow for national and international comparisons. Outcome measurement is key to understanding different models of care across countries and, ultimately, patient outcome having controlled for differing patients characteristics., (© The Author(s) 2015.)

Aim: Long-term stability testing of drug candidates in biological matrix is a key parameter in bioanalytical method validation. The European Bioanalysis Forum formed a Topic Team to evaluate the use of isochronic design for long-term stability testing of large molecules., Method: Isochronic design is based on storage of samples at a reference temperature (below -130°C) where the samples are considered stable. The stability samples are stored at the intended storage temperature and then transferred to the reference temperature, while a set of reference samples is stored the entire storage period at the reference temperature. Stability and reference samples will then be analyzed in one run at the end of the storage period. The mean concentrations of the stability samples are compared either to their nominal concentrations or to the mean concentrations of the reference samples., Conclusion: The design minimizes day-to-day variation, reduces workload and adds to the flexibility in the laboratory.