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Microcirculation is pervasive and orchestrates a profound regulatory cross-talk with the surrounding tissue and organs. Similarly, it is one of the earliest biological systems targeted by environmental stressors and consequently involved in the development and progression of ageing and age-related disease. Microvascular dysfunction, if not targeted, leads to a steady derangement of the phenotype, which cumulates comorbidities and eventually results in a nonrescuable, very high-cardiovascular risk. Along the broad spectrum of pathologies, both shared and distinct molecular pathways and pathophysiological alteration are involved in the disruption of microvascular homeostasis, all pointing to microvascular inflammation as the putative primary culprit. This position paper explores the presence and the detrimental contribution of microvascular inflammation across the whole spectrum of chronic age-related diseases, which characterise the 21st-century healthcare landscape. The manuscript aims to strongly affirm the centrality of microvascular inflammation by recapitulating the current evidence and providing a clear synoptic view of the whole cardiometabolic derangement. Indeed, there is an urgent need for further mechanistic exploration to identify clear, very early or disease-specific molecular targets to provide an effective therapeutic strategy against the otherwise unstoppable rising prevalence of age-related diseases.

Microcirculation is pervasive and orchestrates a profound regulatory cross-talk with the surrounding tissue and organs. Similarly, it is one of the earliest biological systems targeted by environmental stressors and consequently involved in the development and progression of ageing and age-related disease. Microvascular dysfunction, if not targeted, leads to a steady derangement of the phenotype, which cumulates comorbidities and eventually results in a nonrescuable, very high-cardiovascular risk. Along the broad spectrum of pathologies, both shared and distinct molecular pathways and pathophysiological alteration are involved in the disruption of microvascular homeostasis, all pointing to microvascular inflammation as the putative primary culprit. This position paper explores the presence and the detrimental contribution of microvascular inflammation across the whole spectrum of chronic age-related diseases, which characterise the 21st-century healthcare landscape. The manuscript aims to strongly affirm the centrality of microvascular inflammation by recapitulating the current evidence and providing a clear synoptic view of the whole cardiometabolic derangement. Indeed, there is an urgent need for further mechanistic exploration to identify clear, very early or disease-specific molecular targets to provide an effective therapeutic strategy against the otherwise unstoppable rising prevalence of age-related diseases.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a hematological malignancy characterized by recurrent skin nodules, an aggressive clinical course with rapid involvement of hematological organs, and a poor prognosis with overall survival. The rarity of the disease results in a few large-scale studies, a lack of controlled clinical trials for its management, and a lack of evidence-based guidelines. Here, we present a review of unmet clinical needs on the management of BPDCN by a panel of eleven experts involved in the research and clinical practice of BPDCN. Recommendations and proposals were achieved by multiple-step formalized procedures to reach a consensus after a comprehensive analysis of the scientific literature. The panel analyzed the critical issues of diagnostic pathway, prognostic stratification, therapy for young and fit patients and elderly and unfit patients, indication for allotransplant and for autotransplant, indication for central nervous system prophylaxis, and management of pediatric BPDCN patients. For each of these issues, consensus opinions were provided and, when appropriate, proposals for advancement in clinical practice were addressed. The hope is that this comprehensive overview will serve to improve the practice of BPDCN and inform the design and implementation of new studies in the field.

Excluding oligo-, di-, monosaccharides and polyols (FODMAPs) from the diet is increasingly being used to treat children with gastrointestinal complaints. The aim of this position paper is to review the available evidence on the safety and efficacy of its use in children and provide expert guidance regarding practical aspects in case its use is considered. Members of the Gastroenterology Committee, the Nutrition Committee and the Allied Health Professionals Committee of the European Society for Pediatric Gastroenterology Hepatology and Nutrition contributed to this position paper. Clinical questions regarding initiation, introduction, duration, weaning, monitoring, professional guidance, safety and risks of the diet are addressed. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. The systematic literature search revealed that the low-FODMAP diet has not been comprehensively studied in children. Indications and contraindications of the use of the diet in different pediatric gastroenterological conditions are discussed and practical recommendations are formulated. There is scarce evidence to support the use of a low-FODMAP diet in children with Irritable Bowel Syndrome and no evidence to recommend its use in other gastrointestinal diseases and complaints in children. Awareness of how and when to use the diet is crucial, as a restrictive diet may impact nutritional adequacy and/or promote distorted eating in vulnerable subjects. The present article provides practical safety tips to be applied when the low-FODMAP diet is considered in children.

Objectives: Given a lack of a systematic approach to the use of breath testing in paediatric patients, the aim of this position paper is to provide expert guidance regarding the indications for its use and practical considerations to optimise its utility and safety. Methods: Nine clinical questions regarding methodology, interpretation, and specific indications of breath testing and treatment of carbohydrate malabsorption were addressed by members of the Gastroenterology Committee (GIC) of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN). A systematic literature search was performed from 1983 to 2020 using PubMed, the MEDLINE and Cochrane Database of Systematic Reviews. Grading of Recommendations, Assessment, Development, and Evaluation was applied to evaluate the outcomes. During a consensus meeting, all recommendations were discussed and finalised. In the absence of evidence from randomised controlled trials, recommendations reflect the expert opinion of the authors. Results: A total of 22 recommendations were voted on using the nominal voting technique. At first, recommendations on prerequisites and preparation for as well as on interpretation of breath tests are given. Then, recommendations on the usefulness of H2-lactose breath testing, H2-fructose breath testing as well as of breath tests for other types of carbohydrate malabsorption are provided. Furthermore, breath testing is recommended to diagnose small intestinal bacterial overgrowth (SIBO), to control for success of Helicobacter pylori eradication therapy and to diagnose and monitor therapy of exocrine pancreatic insufficiency, but not to estimate oro-caecal transit time (OCTT) or to diagnose and follow-up on celiac disease. Conclusions: Breath tests are frequently used in paediatric gastroenterology mainly assessing carbohydrate malabsorption, but also in the diagnosis of small intestinal overgrowth, fat malabsorption, H. pylori infection as well as for measuring g

Button batteries (BB) remain a health hazard to children as ingestion might lead to life-threatening complications, especially if the battery is impacted in the esophagus. Worldwide initiatives have been set up in order to prevent and also timely diagnose and manage BB ingestions. A European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) task force for BB ingestions has been founded, which aimed to contribute to reducing the health risks related to this event. It is important to focus on the European setting, next to other worldwide initiatives, to develop and implement effective management strategies. As one of the first initiatives of the ESPGHAN task force, this ESPGHAN position paper has been written. The literature is summarized, and prevention strategies are discussed focusing on some controversial topics. An algorithm for the diagnosis and management of BB ingestions is presented and compared to previous guidelines (NASPGHAN, National Poison Center). In agreement with earlier guidelines, immediate localization of the BB is important and in case of esophageal impaction, the BB should be removed instantly (preferably <2 hours). Honey and sucralfate can be considered in ingestions <= 12 hours while waiting for endoscopic removal but should not delay it. In case of delayed diagnosis (first confirmation of the BB on X-ray >12 hours after ingestion or time point of removal >12 hours after ingestion) and esophageal impaction the guideline suggests to perform a CT scan in order to evaluate for vascular injury before removing the battery. In delayed diagnosis, even if the battery has passed the esophagus, endoscopy to screen for esophageal damage and a CT scan to rule out vascular injury should be considered even in asymptomatic children. In asymptomatic patients with early diagnosis (<= 12 hours after ingestion) and position of the BB beyond the esophagus, one can monitor with repeat X-ray (if not already evacuated in stool) in 7 to 14 day

Button batteries (BB) remain a health hazard to children as ingestion might lead to life-threatening complications, especially if the battery is impacted in the esophagus. Worldwide initiatives have been set up in order to prevent and also timely diagnose and manage BB ingestions. A European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) task force for BB ingestions has been founded, which aimed to contribute to reducing the health risks related to this event. It is important to focus on the European setting, next to other worldwide initiatives, to develop and implement effective management strategies. As one of the first initiatives of the ESPGHAN task force, this ESPGHAN position paper has been written. The literature is summarized, and prevention strategies are discussed focusing on some controversial topics. An algorithm for the diagnosis and management of BB ingestions is presented and compared to previous guidelines (NASPGHAN, National Poison Center). In agreement with earlier guidelines, immediate localization of the BB is important and in case of esophageal impaction, the BB should be removed instantly (preferably <2 hours). Honey and sucralfate can be considered in ingestions <= 12 hours while waiting for endoscopic removal but should not delay it. In case of delayed diagnosis (first confirmation of the BB on X-ray >12 hours after ingestion or time point of removal >12 hours after ingestion) and esophageal impaction the guideline suggests to perform a CT scan in order to evaluate for vascular injury before removing the battery. In delayed diagnosis, even if the battery has passed the esophagus, endoscopy to screen for esophageal damage and a CT scan to rule out vascular injury should be considered even in asymptomatic children. In asymptomatic patients with early diagnosis (<= 12 hours after ingestion) and position of the BB beyond the esophagus, one can monitor with repeat X-ray (if not already evacuated in stool) in 7 to 14 day

The present paper provides an update of previous recommendations on Home Blood Pressure Monitoring from the European Society of Hypertension (ESH) Working Group on Blood Pressure Monitoring and Cardiovascular Variability sequentially published in years 2000, 2008 and 2010. This update has taken into account new evidence in this field, including a recent statement by the American Heart association, as well as technological developments, which have occurred over the past 20 years. The present document has been developed by the same ESH Working Group with inputs from an international team of experts, and has been endorsed by the ESH.

Objectives: The aim of the study was to review the evidence regarding the clinical use and value of fecal calprotectin (FC) measurements in different gastrointestinal disorders in children. Methods: A literature search was conducted in the PubMed, MEDLINE, EMBASE, and Cochrane databases until October 31, 2019. Subtopics were identified and each assigned to individual authors. Results: A total of 28 recommendations were voted on using the nominal voting technique. Recommendations are given related to sampling, measurement methods, and results interpretation. The 14 authors anonymously voted on each recommendation using a 9-point scale (1 strongly disagree to 9 fully agree). Consensus was considered achieved if at least 75% of the authors voted 6, 7, 8, or 9. Conclusions: Consensus was reached for all recommendations. Limitations for the use of FC in clinical practice include variability in extraction methodology, performance of test kits as well as the need to establish local reference ranges because of the influence of individual factors, such as age, diet, microbiota, and drugs. The main utility of FC measurement at present is in the diagnosis and monitoring of inflammatory bowel disease (IBD) as well as to differentiate it from functional gastrointestinal disorders (FAPDs). FC, however, has neither utility in the diagnosis of infantile colic nor to differentiate between functional and organic constipation. A rise in FC concentration, may alert to the risk of developing necrotizing enterocolitis and help identifying gastrointestinal involvement in children with Henoch-Schonlein purpura. FC measurement is of little value in Cow's Milk Protein Allergy, coeliac disease (CD), and cystic fibrosis. FC does neither help to distinguish bacterial from viral acute gastroenteritis (AGE), nor to diagnose Helicobacter Pylori infection, small intestinal bacterial overgrowth (SIBO), acute appendicitis (AA), or intestinal polyps.

Hypertension constitutes a major risk factor for heart failure with preserved ejection fraction (HFpEF). HFpEF is a prevalent clinical syndrome with increased cardiovascular morbidity and mortality. Specific guideline-directed medical therapy (GDMT) for HFpEF is not established due to lack of positive outcome data from randomized controlled trials (RCTs) and limitations of available studies. Although available evidence is limited, control of blood pressure (BP) is widely regarded as central to the prevention and clinical care in HFpEF. Thus, in current guidelines including the 2018 European Society of Cardiology (ESC) and European Society of Hypertension (ESH) Guidelines, blockade of the renin-angiotensin system (RAS) with either angiotensinconverting enzyme inhibitors or angiotensin receptor blockers provides the backbone of BP-lowering therapy in hypertensive patients. Although superiority of RAS blockers has not been clearly shown in dedicated RCTs designed for HFpEF, we propose that this core drug treatment strategy is also applicable for hypertensive patients with HFpEF with the addition of some modifications. The latter apply to the use of spironolactone apart from the treatment of resistant hypertension and the use of the angiotensin receptor neprilysin inhibitor. In addition, novel agents such as sodium-glucose co-transporter-2 inhibitors, currently already indicated for high-risk patients with diabetes to reduce heart failure hospitalizations, and finerenone represent promising therapies and results from ongoing RCTs are eagerly awaited. The development of an effective and practical classification of HFpEF phenotypes and GDMT through dedicated high-quality RCTs are major unmet needs in hypertension research and calls for action.

Objectives: The aim of the study was to review the evidence regarding the clinical use and value of fecal calprotectin (FC) measurements in different gastrointestinal disorders in children. Methods: A literature search was conducted in the PubMed, MEDLINE, EMBASE, and Cochrane databases until October 31, 2019. Subtopics were identified and each assigned to individual authors. Results: A total of 28 recommendations were voted on using the nominal voting technique. Recommendations are given related to sampling, measurement methods, and results interpretation. The 14 authors anonymously voted on each recommendation using a 9-point scale (1 strongly disagree to 9 fully agree). Consensus was considered achieved if at least 75% of the authors voted 6, 7, 8, or 9. Conclusions: Consensus was reached for all recommendations. Limitations for the use of FC in clinical practice include variability in extraction methodology, performance of test kits as well as the need to establish local reference ranges because of the influence of individual factors, such as age, diet, microbiota, and drugs. The main utility of FC measurement at present is in the diagnosis and monitoring of inflammatory bowel disease (IBD) as well as to differentiate it from functional gastrointestinal disorders (FAPDs). FC, however, has neither utility in the diagnosis of infantile colic nor to differentiate between functional and organic constipation. A rise in FC concentration, may alert to the risk of developing necrotizing enterocolitis and help identifying gastrointestinal involvement in children with Henoch-Schonlein purpura. FC measurement is of little value in Cow's Milk Protein Allergy, coeliac disease (CD), and cystic fibrosis. FC does neither help to distinguish bacterial from viral acute gastroenteritis (AGE), nor to diagnose Helicobacter Pylori infection, small intestinal bacterial overgrowth (SIBO), acute appendicitis (AA), or intestinal polyps.

Cardiovascular magnetic resonance (CMR) has emerged as an accurate diagnostic technique for the evaluation of patients with cardiac disease in the majority of clinical settings, thanks to an established additional diagnostic and prognostic value. This document has been developed by a joined group of experts of the Italian Society of Cardiology (SIC) and Italian Society of Radiology (SIRM) to provide a summary about the current state of technology and clinical applications of CMR, to improve the clinical diagnostic pathways and to promote its inclusion in clinical practice. The writing committee consisted of members and experts of both societies in order to develop a more integrated approach in the field of cardiac imaging. This section 2 will cover myocarditis, pericardial disease, cardiomyopathies and valvular heart disease.

Objectives: Jejunal tube feeding (JTF) is increasingly becoming the standard of care for children in whom gastric tube feeding is insufficient to achieve caloric needs. Given a lack of a systematic approach to the care of JTF in paediatric patients, the aim of this position paper is to provide expert guidance regarding the indications for its use and practical considerations to optimize its utility and safety. Methods: A group of members of the Gastroenterology and Nutrition Committees of the European Society of Paediatric Gastroenterology Hepatology and Nutrition and of invited experts in the field was formed in September 2016 to produce this clinical guide. Seventeen clinical questions treating indications and contraindications, investigations before placement, techniques of placement, suitable feeds and feeding regimen, weaning from JTF, complications, long-term care, and ethical considerations were addressed. A systematic literature search was performed from 1982 to November 2018 using PubMed, the MEDLINE, and Cochrane Database of Systematic Reviews. Grading of Recommendations, Assessment, Development, and Evaluation was applied to evaluate the outcomes. During a consensus meeting, all recommendations were discussed and finalized. In the absence of evidence from randomized controlled trials, recommendations reflect the expert opinion of the authors. Results: A total of 33 recommendations were voted on using the nominal voting technique. Conclusions: JTF is a safe and effective means of enteral feeding when gastric feeding is insufficient to meet caloric needs or is not possible. The decision to place a jejunal tube has to be made by close cooperation of a multidisciplinary team providing active follow-up and care.

Objectives: Jejunal tube feeding (JTF) is increasingly becoming the standard of care for children in whom gastric tube feeding is insufficient to achieve caloric needs. Given a lack of a systematic approach to the care of JTF in paediatric patients, the aim of this position paper is to provide expert guidance regarding the indications for its use and practical considerations to optimize its utility and safety. Methods: A group of members of the Gastroenterology and Nutrition Committees of the European Society of Paediatric Gastroenterology Hepatology and Nutrition and of invited experts in the field was formed in September 2016 to produce this clinical guide. Seventeen clinical questions treating indications and contraindications, investigations before placement, techniques of placement, suitable feeds and feeding regimen, weaning from JTF, complications, long-term care, and ethical considerations were addressed. A systematic literature search was performed from 1982 to November 2018 using PubMed, the MEDLINE, and Cochrane Database of Systematic Reviews. Grading of Recommendations, Assessment, Development, and Evaluation was applied to evaluate the outcomes. During a consensus meeting, all recommendations were discussed and finalized. In the absence of evidence from randomized controlled trials, recommendations reflect the expert opinion of the authors. Results: A total of 33 recommendations were voted on using the nominal voting technique. Conclusions: JTF is a safe and effective means of enteral feeding when gastric feeding is insufficient to meet caloric needs or is not possible. The decision to place a jejunal tube has to be made by close cooperation of a multidisciplinary team providing active follow-up and care.

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.

Levosimendan is an inodilator that promotes cardiac contractility primarily via calcium sensitization of cardiac troponin C and vasodilatation via opening of adenosine triphosphate-sensitive potassium (KATP) channels in vascular smooth muscle cells; the drug also exerts organ-protective effects via a similar effect on mitochondrial KATP channels. This pharmacological profile identifies levosimendan as a drug that may have applications in a wide range of critical illness situations encountered in intensive care unit medicine: hemodynamic support in cardiogenic or septic shock; weaning from mechanical ventilation or from extracorporeal membrane oxygenation; and in the context of cardiorenal syndrome. This review, authored by experts from 9 European countries (Austria, Belgium, Czech republic, Finland, France, Germany, Italy, Sweden, and Switzerland) examines the clinical and experimental data for levosimendan in these situations and concludes that, in most instances, the evidence is affirmative and encouraging, which is not the case with other cardio- and vasoactive drugs routinely used in the intensive care unit. The size of the available studies is, however, limited and the data are in need of verification in larger controlled trials. Some proposals are offered for the aims and designs of these additional studies. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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.

Vitamin K deficiency bleeding (VKDB) due to physiologically low vitamin K plasma concentrations is a serious risk for newborn and young infants and can be largely prevented by adequate vitamin K supplementation. The aim of this position paper is to define the condition, describe the prevalence, discuss current prophylaxis practices and outcomes, and to provide recommendations for the prevention of VKDB in healthy term newborns and infants. All newborn infants should receive vitamin K prophylaxis and the date, dose, and mode of administration should be documented. Parental refusal of vitamin K prophylaxis after adequate information is provided should be recorded especially because of the risk of late VKDB. Healthy newborn infants should either receive 1 mg of vitamin K1 by intramuscular injection at birth; or 3 × 2 mg vitamin K1 orally at birth, at 4 to 6 days and at 4 to 6 weeks; or 2 mg vitamin K1 orally at birth, and a weekly dose of 1 mg orally for 3 months. Intramuscular application is the preferred route for efficiency and reliability of administration. The success of an oral policy depends on compliance with the protocol and this may vary between populations and healthcare settings. If the infant vomits or regurgitates the formulation within 1 hour of administration, repeating the oral dose may be appropriate. The oral route is not appropriate for preterm infants and for newborns who have cholestasis or impaired intestinal absorption or are too unwell to take oral vitamin K1, or those whose mothers have taken medications that interfere with vitamin K metabolism. Parents who receive prenatal education about the importance of vitamin K prophylaxis may be more likely to comply with local procedures.

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.

The consumption of sugars, particularly sugar-sweetened beverages (SSBs; beverages or drinks that contain added caloric sweeteners (ie, sucrose, high-fructose corn syrup, fruit juice concentrates), in European children and adolescents exceeds current recommendations. This is of concern because there is no nutritional requirement for free sugars, and infants have an innate preference for sweet taste, which may be modified and reinforced by pre- and postnatal exposures. Sugar-containing beverages/free sugars increase the risk for overweight/obesity and dental caries, can result in poor nutrient supply and reduced dietary diversity, and may be associated with increased risk of type 2 diabetes mellitus, cardiovascular risk, and other health effects. The term "free sugars," includes all monosaccharides/disaccharides added to foods/beverages by the manufacturer/cook/consumer, plus sugars naturally present in honey/syrups/unsweetened fruit juices and fruit juice concentrates. Sugar naturally present in intact fruits and lactose in amounts naturally present in human milk or infant formula, cow/goat milk, and unsweetened milk products is not free sugar. Intake of free sugars should be reduced and minimised with a desirable goal of <5% energy intake in children and adolescents aged ≥2 to 18 years. Intake should probably be even lower in infants and toddlers <2 years. Healthy approaches to beverage and dietary consumption should be established in infancy, with the aim of preventing negative health effects in later childhood and adulthood. Sugar should preferably be consumed as part of a main meal and in a natural form as human milk, milk, unsweetened dairy products, and fresh fruits, rather than as SSBs, fruit juices, smoothies, and/or sweetened milk products. Free sugars in liquid form should be replaced by water or unsweetened milk drinks. National Authorities should adopt policies aimed at reducing the intake of free sugars in infants, children and adolescents. This may inc

The aim of the present article was to perform a systematic review with meta-analysis of available scientific evidence regarding the role of different intravenous lipid emulsions (ILE) in the pathogenesis of cholestasis and parenteral nutrition-associated liver disease. A systematic review of the literature (up to March 2015) identified 23 randomized controlled trials (RCTs). Of these, 17 were performed in preterm infants or critically ill neonates with a short duration of intervention, 2 in older children with short-term use (following surgery or bone marrow transplantation), 1 in neonates with long-term use, and 3 in infants and children receiving long-term parenteral nutrition (PN). Meta-analysis showed no differences in the rate of cholestasis or bilirubin levels associated with short-term use of different ILEs. Because of high heterogeneity of the long-term studies no meta-analysis could be performed. Available studies found that the use of multicomponent fish oil (FO)-containing ILE compared with pure soya bean oil (SO), ILE-reduced liver enzymes, and bilirubin levels in noncholestatic children on long-term PN and one other RCT found that FO-based ILE-reversed cholestasis in a proportion of patients. The ESPGHAN Committee on Nutrition concludes that there is no evidence of a difference in rates of cholestasis or bilirubin levels between different ILE for short-term use in neonates. The use of multicomponent FO-containing ILE may contribute to a decrease in total bilirubin levels in children with IF on prolonged PN. Well-designed RCTs are, however, lacking and long-term effects have not been determined.

BACKGROUND: Hepatitis E virus (HEV) is endemic in large parts of the developing world. Waterborne transmission of genotypes 1 or 2 commonly causes acute hepatitis, which is usually self limited in healthy individuals. In addition, acute HEV infections also occur outside endemic areas, mostly related to foodborne transmission of HEV genotype 3. A growing number of publications in the last decade have reported chronic infection progressing to cirrhosis in immunosuppressed patients. It has also been suggested that HEV transmission may occur via contaminated blood products. This publication aims to provide recommendations for diagnosis, prevention and treatment of HEV infection, particularly in children after solid organ transplantation (SOT). METHODS: A systematic PubMed literature search on HEV infection from 1990 to January 2016 was performed focusing on paediatric studies. The existing body of evidence was reviewed and recommendations were agreed upon following discussion and unanimous agreement by all members of the ESPGHAN Hepatology Committee during a consensus meeting in January 2016. In the absence of randomized controlled studies these recommendations were considered to be expert opinions.

The proportional recovery rule states that most survivors recover a fixed proportion (approximate to 70%) of lost function after stroke. A strong (negative) correlation between the initial score and subsequent change (outcome minus initial; ie, recovery) is interpreted as empirical support for the proportional recovery rule. However, this rule has recently been critiqued, with a central observation being that the correlation of initial scores with change over time is confounded in the situations in which it is typically assessed. This critique has prompted reassessments of patients' behavioral trajectory following stroke in 2 prominent papers. The first of these, by van der Vliet et al presented an impressive modeling of upper limb deficits following stroke, which avoided the confounded correlation of initial scores with change. The second by Kundert et al reassessed the value of the proportional recovery rule, as classically formulated as the correlation between initial scores and change. They argued that while effective prediction of recovery trajectories of individual patients is not supported by the available evidence, group-level inferences about the existence of proportional recovery are reliable. In this article, we respond to the van der Vliet and Kundert papers by distilling the essence of the argument for why the classic assessment of proportional recovery is confounded. In this respect, we reemphasize the role of mathematical coupling and compression to ceiling in the confounded nature of the correlation of initial scores with change. We further argue that this confound will be present for both individual-level and group-level inference. We then focus on the difficulties that can arise from ceiling effects, even when initial scores are not being correlated with change/recovery. We conclude by emphasizing the need for new techniques to analyze recovery after stroke that are not confounded in the ways highlighted here.

The proportional recovery rule states that most survivors recover a fixed proportion (approximate to 70%) of lost function after stroke. A strong (negative) correlation between the initial score and subsequent change (outcome minus initial; ie, recovery) is interpreted as empirical support for the proportional recovery rule. However, this rule has recently been critiqued, with a central observation being that the correlation of initial scores with change over time is confounded in the situations in which it is typically assessed. This critique has prompted reassessments of patients' behavioral trajectory following stroke in 2 prominent papers. The first of these, by van der Vliet et al presented an impressive modeling of upper limb deficits following stroke, which avoided the confounded correlation of initial scores with change. The second by Kundert et al reassessed the value of the proportional recovery rule, as classically formulated as the correlation between initial scores and change. They argued that while effective prediction of recovery trajectories of individual patients is not supported by the available evidence, group-level inferences about the existence of proportional recovery are reliable. In this article, we respond to the van der Vliet and Kundert papers by distilling the essence of the argument for why the classic assessment of proportional recovery is confounded. In this respect, we reemphasize the role of mathematical coupling and compression to ceiling in the confounded nature of the correlation of initial scores with change. We further argue that this confound will be present for both individual-level and group-level inference. We then focus on the difficulties that can arise from ceiling effects, even when initial scores are not being correlated with change/recovery. We conclude by emphasizing the need for new techniques to analyze recovery after stroke that are not confounded in the ways highlighted here.

Background: The three-dimensional surface imaging system is becoming more common in plastic surgeries. However, few studies have assessed three-dimensional periocular structures and surgical outcomes. This study aimed to propose a standardized three-dimensional anthropometric protocol for the periocular region, investigate its precision and accuracy, and determine the three-dimensional periocular anthropometric norms for young Caucasians. Methods: Thirty-nine healthy young Caucasians (78 eyes) were enrolled. Three-dimensional facial images were obtained with a VECTRA M3 stereophotogrammetry device. Thirty-eight measurements in periocular regions were obtained from these images. Every subject underwent facial surface capture twice to evaluate its precision. A paper ruler was applied to assess its accuracy. Results: Sixty-three percent of measurements in linear distances, curvatures, angles, and indices were found to reach a statistically significant difference between sexes (p <= 0.05, respectively). Across all measurements, the average mean absolute difference was 0.29 mm in linear dimensions, 0.56 mm in curvatures, 1.67 degrees in angles, and 0.02 in indices. In relative error of magnitude, 18 percent of the measurements were determined excellent, 51 percent very good, 31 percent good, and none moderate. The mean value of the paper-ruler scale was 10.01 +/- 0.05 mm, the mean absolute difference value 0.02 mm, and the relative error of magnitude 0.17 percent. Conclusions: This is the first study to propose a detailed and standardized three-dimensional anthropometric protocol for the periocular region and confirm its high precision and accuracy. The results provided novel metric data concerning young Caucasian periocular anthropometry and determined the variability between sexes.

Background: The three-dimensional surface imaging system is becoming more common in plastic surgeries. However, few studies have assessed three-dimensional periocular structures and surgical outcomes. This study aimed to propose a standardized three-dimensional anthropometric protocol for the periocular region, investigate its precision and accuracy, and determine the three-dimensional periocular anthropometric norms for young Caucasians. Methods: Thirty-nine healthy young Caucasians (78 eyes) were enrolled. Three-dimensional facial images were obtained with a VECTRA M3 stereophotogrammetry device. Thirty-eight measurements in periocular regions were obtained from these images. Every subject underwent facial surface capture twice to evaluate its precision. A paper ruler was applied to assess its accuracy. Results: Sixty-three percent of measurements in linear distances, curvatures, angles, and indices were found to reach a statistically significant difference between sexes (p <= 0.05, respectively). Across all measurements, the average mean absolute difference was 0.29 mm in linear dimensions, 0.56 mm in curvatures, 1.67 degrees in angles, and 0.02 in indices. In relative error of magnitude, 18 percent of the measurements were determined excellent, 51 percent very good, 31 percent good, and none moderate. The mean value of the paper-ruler scale was 10.01 +/- 0.05 mm, the mean absolute difference value 0.02 mm, and the relative error of magnitude 0.17 percent. Conclusions: This is the first study to propose a detailed and standardized three-dimensional anthropometric protocol for the periocular region and confirm its high precision and accuracy. The results provided novel metric data concerning young Caucasian periocular anthropometry and determined the variability between sexes.

BACKGROUND: In recent years, acupuncture has gained popularity in the management of cancer-related pain (CRP). This study aims to use bibliometric analysis to investigate the historical development, recent hotspots and research trends in this field. METHODS: The Web of Science Core Collection database was selected as the data source for this study to retrieve and obtain literature related to acupuncture and CRP. Data analyses were performed with CiteSpace and VOSviewer to conduct the bibliometric analysis. RESULTS: This bibliometric analysis was conducted from 2000 to 2022. A total of 664 publications were included in this work. The number of publications has steadily increased over the last 2 decades. The United States has the largest number of published articles (244 papers), while the People's Republic of China has the highest centrality (0.48). The primary research institutions were Memorial Sloan-Kettering Cancer Center, Kyung Hee University and Beijing University of Chinese Medicine. Mao Jun J. was the most prolific author, while Heather Greenlee was the most cited one. The most productive journal was Integrative Cancer Therapies. The most frequent keywords excluding the search subject were "electroacupuncture," "management," "quality of life," "breast cancer," "Aromatase inhibitor," "neuropathic pain," "mechanisms," and "protocol." CONCLUSION: This study explored the application value of acupuncture in the management of CRP with bibliometric analysis, offering an intuitive understanding of this topic and revealing the hotspots and research trends.

Objectives: Hearing loss is common and a major contributor to the global number of years lived with disability. An increasing number of studies have begun to consider the specific psychological processes by which distressing thoughts, emotional experiences and non-adaptive behaviours exert an influence on functioning and health among those who suffer from audiological disorders. Psychological acceptance has recently been proposed to be a core process but has to date not been systematically examined among individuals with hearing problems. This study examined the reliability, factor structure and the validity of the Hearing Acceptance Questionnaire (HAQ). Design: The HAQ was developed from similar questionnaires for other chronic health conditions and was evaluated using data from an online screening of hearing ability (N=1351). Measures included a hearing test (speech-in-noise), standardized and validated self-report measurements of anxiety and depression symptoms (the Hospital Anxiety and Depression scale), hearing related disability (the Amsterdam Inventory of Hearing Disability and Handicap), and quality of life (the Quality of Life Inventory). Factor structure of the HAQ was evaluated with confirmatory factor analysis, and the unique contribution of psychological acceptance in accounting for variance in hearing disability was examined by hierarchical multiple regression analyses. Results: Findings supported the reliability, factor structure and validity of the HAQ. Confirmatory factor analysis supported a two-factor model with one subscale measuring Avoidance with 9 items; alpha = 0.84) and the other Activity Engagement (3 items; alpha = 0.76). Both subscales of the HAQ explained unique variance in disability after hearing ability, depression and anxiety symptoms were statistically taken into account. Theoretical and clinical implications of psychological acceptance in adults with hearing problems are discussed. Conclusions: This paper evaluated the psychometric

OBJECTIVES: To understand how pain-related cognitions predict and influence treatment retention and adherence during and after a multidisciplinary rehabilitation program. METHODS: Electronic databases including Medline, CINAHL, PsycINFO, Academic Search Complete, and Scopus were used to search three combinations of keywords: chronic pain, beliefs, and treatment adherence. RESULTS: The search strategy yielded 591 results, with an additional 12 studies identified through reference screening. 81 full-text papers were assessed for eligibility and 10 papers met the inclusion and exclusion criteria for this review. The pain-related beliefs that have been measured in relation to treatment adherence include: pain-specific self-efficacy, perceived disability, catastrophizing, control beliefs, fear-avoidance beliefs, perceived benefits and barriers, as well as other less commonly measured beliefs. The most common pain-related belief investigated in relation to treatment adherence was pain-related self-efficacy. Findings for the pain-related beliefs investigated among the studies were mixed. Collectively, all of the aforementioned pain-related beliefs, excluding control beliefs, were found to influence treatment adherence behaviours. DISCUSSION: The findings suggest that treatment adherence is determined by a combination of pain-related beliefs either supporting or inhibiting chronic pain patients' ability to adhere to treatment recommendations over time. In the studies reviewed, self-efficacy appears to be the most commonly researched predictor of treatment adherence, its effects also influencing other pain-related beliefs. More refined and standardised methodologies, consistent descriptions of pain-related beliefs and methods of measurement will improve our understanding of adherence behaviours.

Concurrent training, commonly acknowledged as a training method where strength and endurance training are completed complementary to each other, is a strategy often implemented in endurance cyclists' and runners' programs to improve physiological determinants of success such as exercise economy. Although concurrent training methods and strategies have been examined to a large extent in endurance cyclists and runners, literature examining optimal concurrent training methods to improve physiological variables in long-distance triathletes is minimal, leaving optimal programming relatively unknown. This practical applications paper identifies and outlines current concepts and considerations regarding concurrent training for long-distance triathletes including mechanisms contributing to improved performance, muscle and movement patterns used, exercise selection, load, velocity of movement, scheduling, frequency, and duration of training. Common misconceptions related to concurrent training are also identified and practical considerations for the application of concurrent training for coaches, athletes, and other professionals to improve all 3 disciplines of triathlon are discussed.

Objectives: The main aim of this study was to determine the impact on clinical practice of the first European Society of Gastroenterology, Hepatology, and Nutrition (ESPGHAN) position paper on the diagnosis and management of nutritional and gastrointestinal problems in children with neurological impairment (NI). Methods: In this pilot-study, a web-based questionnaire was distributed between November, 2019 and June, 2020, amongst ESPGHAN members using the ESPGHAN newsletter. Fifteen questions covered the most relevant aspects on nutritional management and gastrointestinal issues of children with NI. A descriptive analysis of responses was performed. Results: A total of 150 health professionals from 23 countries responded to the survey. A considerable variation in clinical practice concerning many aspects of nutritional and gastrointestinal management of children with NI was observed. The most frequently used method for diagnosing oropharyngeal dysfunction was the direct observation of meals with or without the use of standardised scores (n = 103). Anthropometric measurements were the most commonly used tools for assessing nutritional status (n = 111). The best treatment for gastroesophageal reflux disease (GERD) was considered to be proton pump inhibitor therapy by most (n = 116) participants. Regarding tube feeding, nearly all respondents (n = 114) agreed that gastrostomy is the best enteral access to be used for long-term enteral feeding. Fundoplication was indicated at the time of gastrostomy placement especially in case of uncontrolled GERD. Conclusions: More studies are required to address open questions on adequate management of children with NI. Identifying knowledge gaps paves the way for developing updated recommendations and improving patient care.

OBJECTIVE: To explore whether placebo surgery controlled trials achieve what they set out to do by investigating discrepancy between projected and actual design aspects of trials identified through systematic review methods. SUMMARY BACKGROUND: Interest in placebo surgery controlled trials is growing in response to concerns regarding unnecessary surgery and the societal cost of low-value healthcare. As questions about the justifiability of using placebo controls in surgery have been addressed, attention is now being paid to more practical concerns. METHODS: Six databases were searched from inception - May 2020 (MEDLINE, Embase, Emcare, APA PsycInfo, CINAHL, Cochrane Library). Placebo surgery controlled trials with a published protocol were included. Three authors extracted "projected" design aspects from protocols and "actual" design aspects from main findings papers. Absolute and relative difference between projected and actual design aspects were presented for each trial. Trials were grouped according to whether they met their target sample size ("completed") and were concluded in a timely fashion. Pairs of authors assessed risk of bias. RESULTS: Of 24 trials with data available to analyse; 3 were completed and concluded within target timeframe; 10 were completed and concluded outside the target timeline; 4 were completed without clear target timeframes; 2 were incomplete and concluded within the target framework; 5 were incomplete and concluded outside the target timeline. Trials which reached the recruitment target underestimated trial duration by 88% and number of recruitment sites by 87%. CONCLUSIONS: Trialists need to factor additional time and sites into future placebo surgery controlled trials. A robust reporting framework of projected and actual trial design is imperative for trialists to learn from their predecessors. REVIEW REGISTRATION: PROSPERO (CRD42019133296).

This overview aims to create an understanding of the nutritional issues concerning patients with cancer and provide evidence-based practical guidance to healthcare professionals (physicians, nurses, and dietitians), caregivers, and all others involved in the care of patients with cancer. The focus of this paper is therefore on providing a simple guide for daily clinical practice. The theoretical background and in-depth comprehensive reviews of malnutrition are described elsewhere. Nutrition plays a crucial role in cancer care. It affects treatment tolerability, outcomes, and quality of life. However, a focus on nutrition is still lacking among oncologists because of insufficient training in nutrition topics received during graduate and postgraduate training and an underestimation of its importance. The consequences of the disease and its treatment, such as anorexia-sarcopenia-cachexia, are therefore still often overlooked, underdiagnosed, and undertreated. The authors have summarized the most important challenges, evidence-based recommendations, and common clinical scenarios to bridge the gap between comprehensive guidelines and clinical practice, where brief concrete advice is preferred to systematic reviews. Furthermore, an easy applicable overview is provided, which can be used as a guide during daily routines.

This overview aims to create an understanding of the nutritional issues concerning patients with cancer and provide evidence-based practical guidance to healthcare professionals (physicians, nurses, and dietitians), caregivers, and all others involved in the care of patients with cancer. The focus of this paper is therefore on providing a simple guide for daily clinical practice. The theoretical background and in-depth comprehensive reviews of malnutrition are described elsewhere. Nutrition plays a crucial role in cancer care. It affects treatment tolerability, outcomes, and quality of life. However, a focus on nutrition is still lacking among oncologists because of insufficient training in nutrition topics received during graduate and postgraduate training and an underestimation of its importance. The consequences of the disease and its treatment, such as anorexia-sarcopenia-cachexia, are therefore still often overlooked, underdiagnosed, and undertreated. The authors have summarized the most important challenges, evidence-based recommendations, and common clinical scenarios to bridge the gap between comprehensive guidelines and clinical practice, where brief concrete advice is preferred to systematic reviews. Furthermore, an easy applicable overview is provided, which can be used as a guide during daily routines.

This overview aims to create an understanding of the nutritional issues concerning patients with cancer and provide evidence-based practical guidance to healthcare professionals (physicians, nurses, and dietitians), caregivers, and all others involved in the care of patients with cancer. The focus of this paper is therefore on providing a simple guide for daily clinical practice. The theoretical background and in-depth comprehensive reviews of malnutrition are described elsewhere. Nutrition plays a crucial role in cancer care. It affects treatment tolerability, outcomes, and quality of life. However, a focus on nutrition is still lacking among oncologists because of insufficient training in nutrition topics received during graduate and postgraduate training and an underestimation of its importance. The consequences of the disease and its treatment, such as anorexia-sarcopenia-cachexia, are therefore still often overlooked, underdiagnosed, and undertreated. The authors have summarized the most important challenges, evidence-based recommendations, and common clinical scenarios to bridge the gap between comprehensive guidelines and clinical practice, where brief concrete advice is preferred to systematic reviews. Furthermore, an easy applicable overview is provided, which can be used as a guide during daily routines.

Concurrent training, commonly acknowledged as a training method where strength and endurance training are completed complementary to each other, is a strategy often implemented in endurance cyclists' and runners' programs to improve physiological determinants of success such as exercise economy. Although concurrent training methods and strategies have been examined to a large extent in endurance cyclists and runners, literature examining optimal concurrent training methods to improve physiological variables in long-distance triathletes is minimal, leaving optimal programming relatively unknown. This practical applications paper identifies and outlines current concepts and considerations regarding concurrent training for long-distance triathletes including mechanisms contributing to improved performance, muscle and movement patterns used, exercise selection, load, velocity of movement, scheduling, frequency, and duration of training. Common misconceptions related to concurrent training are also identified and practical considerations for the application of concurrent training for coaches, athletes, and other professionals to improve all 3 disciplines of triathlon are discussed.

This overview aims to create an understanding of the nutritional issues concerning patients with cancer and provide evidence-based practical guidance to healthcare professionals (physicians, nurses, and dietitians), caregivers, and all others involved in the care of patients with cancer. The focus of this paper is therefore on providing a simple guide for daily clinical practice. The theoretical background and in-depth comprehensive reviews of malnutrition are described elsewhere. Nutrition plays a crucial role in cancer care. It affects treatment tolerability, outcomes, and quality of life. However, a focus on nutrition is still lacking among oncologists because of insufficient training in nutrition topics received during graduate and postgraduate training and an underestimation of its importance. The consequences of the disease and its treatment, such as anorexia-sarcopenia-cachexia, are therefore still often overlooked, underdiagnosed, and undertreated. The authors have summarized the most important challenges, evidence-based recommendations, and common clinical scenarios to bridge the gap between comprehensive guidelines and clinical practice, where brief concrete advice is preferred to systematic reviews. Furthermore, an easy applicable overview is provided, which can be used as a guide during daily routines.

Objectives: The main aim of this study was to determine the impact on clinical practice of the first European Society of Gastroenterology, Hepatology, and Nutrition (ESPGHAN) position paper on the diagnosis and management of nutritional and gastrointestinal problems in children with neurological impairment (NI). Methods: In this pilot-study, a web-based questionnaire was distributed between November, 2019 and June, 2020, amongst ESPGHAN members using the ESPGHAN newsletter. Fifteen questions covered the most relevant aspects on nutritional management and gastrointestinal issues of children with NI. A descriptive analysis of responses was performed. Results: A total of 150 health professionals from 23 countries responded to the survey. A considerable variation in clinical practice concerning many aspects of nutritional and gastrointestinal management of children with NI was observed. The most frequently used method for diagnosing oropharyngeal dysfunction was the direct observation of meals with or without the use of standardised scores (n = 103). Anthropometric measurements were the most commonly used tools for assessing nutritional status (n = 111). The best treatment for gastroesophageal reflux disease (GERD) was considered to be proton pump inhibitor therapy by most (n = 116) participants. Regarding tube feeding, nearly all respondents (n = 114) agreed that gastrostomy is the best enteral access to be used for long-term enteral feeding. Fundoplication was indicated at the time of gastrostomy placement especially in case of uncontrolled GERD. Conclusions: More studies are required to address open questions on adequate management of children with NI. Identifying knowledge gaps paves the way for developing updated recommendations and improving patient care.

Purpose: Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is now performed in many trauma centers, it is used at more than 250 hospitals in the United States and there is an increase rate of publications with the experience in these centers, but there is a gap of knowledge regarding the use of REBOA in Latin-America. This paper endeavors to describe the utilization of REBOA at a high level Latin-American Trauma Center and the transition from a large caliber to a low-profile device with the concomitant reduction in the groin access complications. Methods: A prospective, observational, single-center study was conducted. We included all trauma patients who underwent REBOA. We recorded data from admission parameters, complications, and clinical outcomes. Results: Fifty patients were included. Most of the REBOA catheters were inserted in the operating room [47 (94%)], and the arterial access was done by surgical cutdown [40 (80%)]. All the complications were associated with the catheter of 11 Fr Sheath used in 36 patients [n = 8/36 (22%) vs. n = 0/14 (0%); P = 0.05]. Conclusion: REBOA can be used safely in blunt or penetrating thoracic, abdominal, and pelvic trauma. The insertion of a 7 Fr Sheath was associated with lower complications, so its use should be preferred over larger calibers.

This overview aims to create an understanding of the nutritional issues concerning patients with cancer and provide evidence-based practical guidance to healthcare professionals (physicians, nurses, and dietitians), caregivers, and all others involved in the care of patients with cancer. The focus of this paper is therefore on providing a simple guide for daily clinical practice. The theoretical background and in-depth comprehensive reviews of malnutrition are described elsewhere. Nutrition plays a crucial role in cancer care. It affects treatment tolerability, outcomes, and quality of life. However, a focus on nutrition is still lacking among oncologists because of insufficient training in nutrition topics received during graduate and postgraduate training and an underestimation of its importance. The consequences of the disease and its treatment, such as anorexia-sarcopenia-cachexia, are therefore still often overlooked, underdiagnosed, and undertreated. The authors have summarized the most important challenges, evidence-based recommendations, and common clinical scenarios to bridge the gap between comprehensive guidelines and clinical practice, where brief concrete advice is preferred to systematic reviews. Furthermore, an easy applicable overview is provided, which can be used as a guide during daily routines.

Objectives: We recently developed a transdiagnostic exposure treatment (the hybrid treatment) for chronic pain patients with concurrent emotional difficulties. This paper investigates the hypothesized treatment processes, specifically: (1) if changes on pain-related dysregulation (catastrophizing, fear-avoidance, and nonacceptance of pain) and general emotion dysregulation (difficulties to regulate a broad spectrum of emotional responses) mediate effects on outcomes; and (2) if mediation is more pronounced for patients who score higher on these processes pretreatment. Materials and Methods: Structural equation modeling for longitudinal data using the full intention-to-treat sample was used to test whether proposed variables mediated the effect of the hybrid treatment (n=58) compared with a guided internet-delivered pain management treatment based on cognitive-behavioral principles (n=57) on pain interference and depressive symptoms at the 9-month follow-up. To make full use of the multiple process measures collected in the trial, we modeled mediators as 2 continuous latent variables: pain-related dysregulation and general emotion dysregulation. Results: Reduced pain-related dysregulation mediated the effects of treatment on both outcomes, whereas reduced general emotion dysregulation mediated the effects on depressive symptoms only. In the hybrid treatment, the mediated effect was more pronounced for participants who scored higher on pain-related dysregulation pretreatment relative to those who scored lower. Discussion: Our findings provide initial support for the transdiagnostic theoretical underpinnings of the hybrid treatment model. Using a hybrid treatment approach that centers on teaching patients emotion-regulation skills before commencing broad exposure successfully influenced both pain-related dysregulation and general emotion dysregulation, which in turn was associated with better treatment outcomes. It appears central to address these processes in pain pat, Funding Agencies|AFA insurance, Stockholm, Sweden [140356]; Region Ostergotland, Linkoping, Sweden [LIO-724821]; Swedish Foundation for Humanities and Social Sciences, Stockholm, Sweden [P14-0799:1]

BACKGROUND AND PURPOSE: Among patients with a transient ischemic attack or minor ischemic strokes, those with ipsilateral atherosclerotic stenosis of cervicocranial vasculature have the highest risk of recurrent vascular events. METHODS: In the double-blind THALES (The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death) trial, we randomized patients with a noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2-30) or placebo added to aspirin (300-325 mg on day 1 followed by 75-100 mg daily for days 2-30) within 24 hours of symptom onset. The present paper reports a prespecified analysis in patients with and without ipsilateral, potentially causal atherosclerotic stenosis ≥30% of cervicocranial vasculature. The primary end point was time to the occurrence of stroke or death within 30 days. RESULTS: Of 11 016 randomized patients, 2351 (21.3%) patients had an ipsilateral atherosclerotic stenosis. After 30 days, a primary end point occurred in 92/1136 (8.1%) patients with ipsilateral stenosis randomized to ticagrelor and in 132/1215 (10.9%) randomized to placebo (hazard ratio 0.73 [95% CI, 0.56-0.96], P=0.023) resulting in a number needed to treat of 34 (95% CI, 19-171). In patients without ipsilateral stenosis, the corresponding event rate was 211/4387 (4.8%) and 230/4278 (5.4%), respectively (hazard ratio, 0.89 [95% CI, 0.74-1.08]; P=0.23, Pinteraction=0.245). Severe bleeding occurred in 4 (0.4%) and 3 (0.2%) patients with ipsilateral atherosclerotic stenosis on ticagrelor and on placebo, respectively (P=NS), and in 24 (0.5%) and 4 (0.1%), respectively, in 8665 patients without ipsilateral stenosis (hazard ratio=5.87 [95% CI, 2.04-16.9], P=0.001). CONCLUSIONS: In this exploratory analysis comparing ticagrelor added to aspirin to aspirin alone, we found no treatment by ipsilateral atherosclerosis ste

BACKGROUND: People with autism spectrum disorder (ASD) have an increased susceptibility for many chronic health conditions compared with their peers. An increasing number of adolescents are transitioning from pediatric to adult healthcare services. Thus, being able to access appropriate healthcare services that can not only address specific needs of the person but enable them to better manage healthcare conditions and decrease the development of preventable disease is necessary. A systematic review was conducted to identify barriers and enablers of healthcare access for autistic adults. METHODS: The studies included in the review were quantitative and qualitative and were published between 2003 and 2019. The participants for the review are considered to be adults (over 18 years of age) with a primary diagnosis of ASD. RESULTS: In total, 1290 studies were initially identified and 13 studies were included based on the inclusion and exclusion criteria outlined in a previous protocol paper. The analysis of these studies identified areas of concern to access appropriate healthcare, such as clinician knowledge, the environment, and life events. CONCLUSION: Identifying the barriers to healthcare, highlights ways healthcare services can regulate scope of practice, the physical environment, and the process of managing health conditions, thus, autistic adults can strive for optimal health. This review contributes to peer-reviewed evidence for future research and up-to-date information when developing and piloting health interventions for autistic adults. ETHICS AND DISSEMINATION: There are no human participants, data, or tissue being directly studied for the purposes of the review; therefore, ethics approval and consent to participate is not applicable. REGISTRATION AND STATUS: PROSPERO 2018 CRD42018116093.

Objectives: We recently developed a transdiagnostic exposure treatment (the hybrid treatment) for chronic pain patients with concurrent emotional difficulties. This paper investigates the hypothesized treatment processes, specifically: (1) if changes on pain-related dysregulation (catastrophizing, fear-avoidance, and nonacceptance of pain) and general emotion dysregulation (difficulties to regulate a broad spectrum of emotional responses) mediate effects on outcomes; and (2) if mediation is more pronounced for patients who score higher on these processes pretreatment. Materials and Methods: Structural equation modeling for longitudinal data using the full intention-to-treat sample was used to test whether proposed variables mediated the effect of the hybrid treatment (n=58) compared with a guided internet-delivered pain management treatment based on cognitive-behavioral principles (n=57) on pain interference and depressive symptoms at the 9-month follow-up. To make full use of the multiple process measures collected in the trial, we modeled mediators as 2 continuous latent variables: pain-related dysregulation and general emotion dysregulation. Results: Reduced pain-related dysregulation mediated the effects of treatment on both outcomes, whereas reduced general emotion dysregulation mediated the effects on depressive symptoms only. In the hybrid treatment, the mediated effect was more pronounced for participants who scored higher on pain-related dysregulation pretreatment relative to those who scored lower. Discussion: Our findings provide initial support for the transdiagnostic theoretical underpinnings of the hybrid treatment model. Using a hybrid treatment approach that centers on teaching patients emotion-regulation skills before commencing broad exposure successfully influenced both pain-related dysregulation and general emotion dysregulation, which in turn was associated with better treatment outcomes. It appears central to address these processes in pain pat, Funding Agencies|AFA insurance, Stockholm, Sweden [140356]; Region Ostergotland, Linkoping, Sweden [LIO-724821]; Swedish Foundation for Humanities and Social Sciences, Stockholm, Sweden [P14-0799:1]

Objectives: We recently developed a transdiagnostic exposure treatment (the hybrid treatment) for chronic pain patients with concurrent emotional difficulties. This paper investigates the hypothesized treatment processes, specifically: (1) if changes on pain-related dysregulation (catastrophizing, fear-avoidance, and nonacceptance of pain) and general emotion dysregulation (difficulties to regulate a broad spectrum of emotional responses) mediate effects on outcomes; and (2) if mediation is more pronounced for patients who score higher on these processes pretreatment. Materials and Methods: Structural equation modeling for longitudinal data using the full intention-to-treat sample was used to test whether proposed variables mediated the effect of the hybrid treatment (n=58) compared with a guided internet-delivered pain management treatment based on cognitive-behavioral principles (n=57) on pain interference and depressive symptoms at the 9-month follow-up. To make full use of the multiple process measures collected in the trial, we modeled mediators as 2 continuous latent variables: pain-related dysregulation and general emotion dysregulation. Results: Reduced pain-related dysregulation mediated the effects of treatment on both outcomes, whereas reduced general emotion dysregulation mediated the effects on depressive symptoms only. In the hybrid treatment, the mediated effect was more pronounced for participants who scored higher on pain-related dysregulation pretreatment relative to those who scored lower. Discussion: Our findings provide initial support for the transdiagnostic theoretical underpinnings of the hybrid treatment model. Using a hybrid treatment approach that centers on teaching patients emotion-regulation skills before commencing broad exposure successfully influenced both pain-related dysregulation and general emotion dysregulation, which in turn was associated with better treatment outcomes. It appears central to address these processes in pain pat, Funding Agencies|AFA insurance, Stockholm, Sweden [140356]; Region Ostergotland, Linkoping, Sweden [LIO-724821]; Swedish Foundation for Humanities and Social Sciences, Stockholm, Sweden [P14-0799:1]