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Mohamad Miqdady,1,2 Saif AlMutaeri,3 Najwa Alsawi,4 Loie Goronfolah,5 Christos Tzivinikos,6 Hamad Al Hameli,7 David Cremonesini,8 Mohammed Al-Enezi,9 Ahmad Hussain,10 Zainab Al Damerdash,11 Mohammed Al-Biltagi12,13 1American Board of Pediatrics Gastroenterology, Hepatology & Nutrition, Chief Pediatric Gastroenterologist, Hepatology & Nutrition Division, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates; 2College of Medicine & Health Sciences, Khalifa University, Abu Dhabi, United Arab Emirates; 3King Faisal Specialist Hospital & Research Centre, Riyadh, Kingdom of Saudi Arabia; 4Sulaiman Al Habib Private Sector Hospital, Riyadh, Kingdom of Saudi Arabia; 5National Guard Jeddah Government Hospital, Jeddah, Kingdom of Saudi Arabia; 6Al Jalila Children’s Specialty Hospital, Dubai, United Arab Emirates; 7Cleveland Clinic, Abu Dhabi, United Arab Emirates; 8Al Ain Hospital, Al Ain, Abu Dhabi, United Arab Emirates; 9Dar Al-Shefa Hospital, Hawally, Kuwait; 10Amiri Hospital/Salam Hospital, Kuwait City, Kuwait; 11Amiri Hospital, Kuwait City, Kuwait; 12Faculty of Medicine, Tanta University, Tanta, Egypt; 13King Abdullah Medical City, Arabian Gulf University, Dr. Sulaiman Al Habib Medical Group, Manama, Kingdom of BahrainCorrespondence: Mohammed Al-Biltagi, Faculty of Medicine, Tanta University, Tanta, Egypt, Tel +97339545472, Email mbelrem@hotmail.comObjective: This study estimates the budgetary impact of the introduction of amino-acid formula (AAF) as first-line management in the elimination diet of infants with suspected cow milk protein allergy (CMPA) in the Kingdom of Saudi Arabia (KSA), Kuwait, and the United Arab Emirates (UAE) from a health-care payer’s perspective.Methods: A global decision tree model was adapted to compare estimated costs in current practice (extensively hydrolyzed formula [eHF] or soy formula [SF] with the proposed approach of early introduction of AAF as first-line treatment of CMPA in non-breast-fed infants). Model inputs were derived from explorative literature reviews and medical experts’ opinions. All costs were reported in local currency, ie, Saudi Riyal (SAR) for KSA, Kuwaiti Dinar (KWD) for Kuwait, and United Arab Emirates Dirham (AED) for the UAE.Results: Cost savings with the early introduction of AAF were 10% (SAR 15102542) in KSA, 10% (KWD 306565) in Kuwait, 17% (AED 1842018) in the UAE government sector and 13% (AED 4232932) in the UAE private sector. The highest cost reduction was observed in the cost of soy formula (SF), with a 58% reduction both in KSA (SAR 4204540) and UAE public sector (AED 110331). A significant cost reduction in medication costs in Kuwait (37%; KWD 5630) and medical examination costs in the UAE private sector (50%; AED 1508918) was observed.Conclusion: Results indicated that the introduction of AAF as the first line in the management of CMPA is a cost-saving strategy for the Gulf Cooperation Council (GCC) countries—KSA, Kuwait, and UAE— from a health-care payer’s perspective.Keywords: cow’s milk protein allergy, amino acid formula, infants, Kingdom of Saudi Arabia, Kuwait, United Arab Emirates, Arabian Gulf

Background Current data on dual biologic therapy in children are limited. This multicenter study aimed to evaluate the effectiveness and safety of dual therapy in pediatric patients with inflammatory bowel disease (IBD). Methods A retrospective study from 14 centers affiliated with the Pediatric IBD Interest and Porto Groups of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition. Included were children with IBD who underwent combinations of biologic agents or biologic and small molecule therapy for at least 3 months. Demographic, clinical, laboratory, endoscopic, and imaging data were collected. Adverse events were recorded. Results Sixty-two children (35 Crohn’s disease, 27 ulcerative colitis; median age 15.5 [interquartile range, 13.1-16.8] years) were included. They had all failed previous biologic therapies, and 47 (76%) failed at least 2 biologic agents. The dual therapy included an anti-tumor necrosis factor agent and vedolizumab in 30 children (48%), anti-tumor necrosis factor and ustekinumab in 21 (34%) children, vedolizumab and ustekinumab in 8 (13%) children, and tofacitinib with a biologic in 3 (5%) children. Clinical remission was observed in 21 (35%), 30 (50%), and 38 (63%) children at 3, 6, and 12 months, respectively. Normalization of C-reactive protein and decrease in fecal calprotectin to Conclusions Dual biologic therapy may be effective in children with refractory IBD. The potential efficacy should be weighed against the risk of serious adverse events.

OBJECTIVES: To systematically review the current evidence on Helicobacter pylori-negative chronic gastritis including natural history, available therapies and outcomes. METHODS: Articles providing data on the prevalence, treatment or outcomes of Helicobacter pylori-negative gastritis were identified through a systematic search in the MEDLINE and EMBASE databases. All original research articles from human studies until October 31, 2021, were included. RESULTS: A total of 54 studies were included consisted of eosinophilic gastritis (n = 9), autoimmune gastritis (n = 11), collagenous gastritis (n = 16), focally enhanced gastritis (n = 6), lymphocytic gastritis (n = 5) and other causes including idiopathic gastritis and chronic renal failure related (n = 7). Most of the included studies were either cross-sectional or longitudinal cohorts except for collagenous gastritis, which mainly included case reports and case series. The prevalence of paediatric eosinophilic gastritis ranges between 5 and 7/100,000 and patients have generally favourable outcome with 50% to 70% clinical and histological response to either corticosteroids or elimination diets. Autoimmune gastritis and collagenous gastritis are extremely rare entities, commonly present with refractory iron deficiency anaemia, while lymphocytic gastritis is relatively common (10%-45%) in children with coeliac disease. Data on treatments and outcomes of autoimmune, collagenous, and focally enhanced gastritis are lacking with limited data implying poor response to therapy in the former 2 diagnoses. CONCLUSIONS: Helicobacter pylori-negative gastritis is uncommonly reported, mainly in small cohorts, mixed adult-paediatric cohorts or as sporadic case reports. As common symptoms are not specific, thus not always result in an endoscopic evaluation, the true prevalence of these distinct disorders may be underestimated, and thus under reported.

BACKGROUNDRare diseases collectively impose significant burden on healthcare systems, especially in underserved regions, like the Middle East, which lack access to genomic diagnostic services and the associated personalized management plans.METHODSWe established a clinical genomics and genetic counselling facility, within a multidisciplinary tertiary paediatric center, in the United Arab Emirates to locally diagnose and manage patients with rare diseases. Clinical genomic investigations included exome-based sequencing, chromosomal microarrays, and/or targeted testing. We assessed the diagnostic yield and implications for clinical management among this population.RESULTSWe present data on 529 patients with rare diseases (47% females; Average age, 4 years) representing 41 countries primarily from the Arabian Peninsula, the Levant, Africa, and Asia. The cumulative diagnostic yield was 35.7% (95% CI, 31.8% - 39.9%) and was higher for genomic sequencing-based testing than chromosomal microarrays (41.2% versus 16.9%, P=0.0001) across all indications, consistent with the higher burden of single gene disorders. Of the 124 Mendelian disorders identified in this cohort, the majority (N = 110) were encountered only once, and those with recessive inheritance accounted for ~60% of sequencing diagnoses. Of patients with positive genetic findings (N = 189), 71.9% were less than 5 years of age, and 65.6% were offered modified management and/or intervention plans. Interestingly, 18.5% of patients with positive genetic findings received delayed diagnoses (age range 7 – 37 years), most likely due to lack of access to genomic investigations in this region. One such genetic finding ended over a 10-year long diagnostic odyssey, leading to a life-threatening diagnosis in one patient, who was then successfully treated using an experimental allogenic bone marrow transplant. Finally, we present cases with candidate genes within regions of homozygosity, likely underlying novel recessive disorders.CONCLUSIONSEarly access to genomic diagnostics for patients with suspected rare disorders in the Middle East is likely to improve clinical outcomes while driving gene discovery in this historically underrepresented population.

Background: Coeliac disease is one of the most prevalent immune-mediated gastrointestinal disorders in children. Aim: To review the incidence and prevalence of paediatric coeliac disease, and their trends, regionally across Europe, overall and according to age at diagnosis. Methods: Systematic review and meta-analysis from January 1, 1950 to December 31, 2019, based on PubMed, CINAHL and the Cochrane Library, searches of grey literature and websites and hand searching of reference lists. A total of 127 eligible studies were included. Results: The prevalence of previously undiagnosed coeliac disease from screening surveys (histology based) ranged from 0.10% to 3.03% (median = 0.70%), with a significantly increasing annual trend (P = 0.029). Prevalence since 2000 was significantly higher in northern Europe (1.60%) than in eastern (0.98%), southern (0.69%) and western (0.60%) Europe. Large increases in the incidence of diagnosed coeliac disease across Europe have reached 50 per 100 000 person-years in Scandinavia, Finland and Spain. The median age at diagnosis increased from 1.9 years before 1990 to 7.6 since 2000. Larger increases in incidence were found in older age groups than in infants and ages

International audience; Thiopurines, alone or in combination with other agents, have a pivotal role in the treatment of specific gastrointestinal and hepatological disorders. In inflammatory bowel disease and autoimmune hepatitis thiopurines have proven their value as steroid sparing agents for the maintenance of remission and may be considered for preventing postoperative Crohn disease recurrence where there is moderate risk of this occurring. Their use with infliximab therapy reduces antibody formation and increases biologic drug levels. The routine clinical use of thiopurines has, however, been questioned due to a number of potential adverse effects. The aim of this article is to provide information regarding the use, and in particular, safety of these agents in clinical practice in the light of such potentially severe, albeit rare, effects.

Commissioned by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), we investigated how European physicians training in these fields are educated in nutrition. A survey on time spent in nutrition training, composition of multidisciplinary nutrition teams, and topics covered during training enrolled 50 participants. A median of 20% of training time was spent on nutrition training during fellowship. Fourteen (28%) had regular nutrition teaching. Thirty-four (68%) were part of a multidisciplinary nutrition team. Twelve (24%) used the ESPGHAN syllabus. Most frequent topics during nutrition training were diagnosis/investigation of failure to thrive, indications/contraindications for enteral feeds, and benefits/risks of enteral/parenteral nutrition. Twenty-seven (54%) had taken a formal nutrition course. Nutrition training in Europe varies and the ESPGHAN training syllabus is not yet implemented Europe-wide. ESPGHAN nutrition summer schools, and Web-based learning may provide appropriate training. We suggest that all patients necessitating nutritional care be treated by multidisciplinary nutrition teams.

What Is Known - Endoscopy Training is becoming an integral part of Paediatric Gastroenterology Training within Europe. - There is a great degree of variation between European endoscopy training in terms of duration, content, procedural volume, assessment during and at the end of training. What Is New? - Achievement of milestones in training more accurately assesses competency compared with procedural number. - Train the trainers’ courses and educational material,such as e-learning and endoscopy simulator training improve a structuredapproachinendoscopy teaching. - Cooperation with the National Paediatric Gastroenterology, Hepatology and Nutrition Societies in Europe will facilitate dissemination, discussion and implementation of results of this position paper.

International audience; 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 gastrointestinal transit times. Interpretation of the results can be challenging and in addition, pertinent symptoms should be considered to evaluate clinical tolerance.

International audience; 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 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 (

Background Atypical antipsychotics (AAP) are commonly prescribed to children and adolescents and are associated with important adverse effects including weight gain and metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) is not only the most common pediatric liver disease but is also associated with serious complications including liver cirrhosis. Objective Given that NAFLD and AAP are associated with metabolic syndrome, we aim to comprehensively examine the association between AAP and NAFLD in children and adolescents. Methods We will conduct a systematic review of studies exploring NAFLD in subjects younger than 18 years on AAP published in English between 1950 and 2020 following the PRISMA (Preferred Reporting items for Systematic Reviews and Meta-Analysis) guidelines. Results A PRISMA flowchart will be used present the study results after comprehensively reviewing studies on NAFLD in children and adolescents taking AAP. The first and second systematic searches will be conducted during December 2021. The results are expected to be published in June 2022. Conclusions This research project will serve as a foundation for future studies and assist in devising interventions and reforming clinical guidelines for using AAP to ensure improved patient safety. International Registered Report Identifier (IRRID) PRR1-10.2196/20168

Atypical Antipsychotic medications are commonly prescribed to children and adolescents and are associated with important adverse effects including weight gain and metabolic syndrome. Non-Alcoholic Fatty Liver Disease (NAFLD) is not only the most common pediatric liver disease, but can also be associated with serious complications including liver cirrhosis. Given that both NAFLD and Atypical Antipsychotics (AAP) are associated with metabolic syndrome, we aimed to comprehensively examine the association between AAP and NAFLD in children and adolescents. We will conduct a systematic review following the PRISMA guidelines, of English-language literature published between 1950 and 2020, exploring NAFLD in subjects younger than 18 years on AAP.

International audience; Gastrointestinal symptoms are common findings in children with severe acute respiratory syndrome coronavirus 2 infection, including vomiting, diarrhoea, abdominal pain, and difficulty in feeding, although these symptoms tend to be mild. The hepato-biliary system and the pancreas may also be involved, usually with a mild elevation of transaminases and, rarely, pancreatitis. In contrast, a late hyper-inflammatory phenomenon, termed multisystem inflammatory syndrome (MIS-C), is characterized by more frequent gastrointestinal manifestations with greater severity, sometimes presenting as peritonitis. Gastrointestinal and hepato-biliary manifestations are probably related to a loss in enterocyte absorption capability and microscopic mucosal damage caused by a viral infection of intestinal epithelial cells, hepatocytes and other cells through the angiotensin conversion enzyme 2 receptor resulting in immune cells activation with subsequent release of inflammatory cytokines. Specific conditions such as inflammatory bowel disease (IBD) and liver transplantation may pose a risk for the more severe presentation of coronavirus disease 2019 (COVID-19) but as adult data accumulate, paediatric data is still limited. The aim of this review is to summarize the current evidence about the effect of COVID-19 on the gastrointestinal system in children, with emphasis on the emerging MIS-C and specific considerations such as patients with IBD and liver transplant recipients.

International audience; Objectives: Digestive perianastomotic ulcerations (DPAU) resembling Crohn disease lesions are long-term complications of intestinal resections, occurring in children and young adults. They are known to be uncommon, severe and difficult to treat.Methods: In the absence of recommendations, we performed a large European survey among the members of the ESPGHAN working group on inflammatory bowel disease (IBD) in order to collect the experience of expert pediatric gastroenterologists on DPAU.Results: Fifty-one patients (29 boys and 22 girls) were identified from 19 centers in 8 countries. Most patients were followed after necrotizing enterocolitis (n = 20) or Hirschsprung disease (n = 11). The anastomosis was performed at a median age (interquartile range) of 6 [1–23] months, and first symptoms occurred 39 [22–106] months after surgery. Anemia was the most prevalent symptom followed by diarrhea, abdominal pain, bloating, and failure to thrive. Hypoalbuminemia, elevated CRP, and fecal calprotectin were common. Deep ulcerations were found in 59% of patients usually proximally to the anastomosis (68%). During a median follow-up of 40 [19–67] months, treatments reported to be the most effective included exclusive enteral nutrition (31/35, 88%), redo anastomosis (18/22, 82%), and alternate antibiotic treatment (37/64, 58%).Conclusions: Unfortunately, persistence of symptoms, failure to thrive, and abnormal laboratory tests at last follow-up in most of patients show the burden of DPAU lacking optimal therapy and incomplete understanding of the pathophysiology.

BACKGROUND: The European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) position paper from 2015 on percutaneous endoscopic gastrostomy (PEG) required updating in the light of recent clinical knowledge and data published in medical journals since 2014. METHODS: A systematic review of medical literature from 2014 to 2020 was carried out. Consensus on the content of the manuscript, including recommendations, was achieved by the authors through electronic and virtual means. The expert opinion of the authors is also expressed in the manuscript when there was a lack of good scientific evidence regarding PEGs in children in the literature. RESULTS: The authors recommend that the indication for a PEG be individualized, and that the decision for PEG insertion is arrived at by a multidisciplinary team (MDT) having considered all appropriate circumstances. Well timed enteral nutrition is optimal to treat faltering growth to avoid complications of malnutrition and body composition. Timing, device choice and method of insertion is dependent on the local expertise and after due consideration with the MDT and family. Major complications such as inadvertent bowel perforation should be avoided by attention to good technique and by ensuring the appropriate experience of the operating team. Feeding can be initiated as early as 3 hours after tube placement in a stable child with iso-osmolar feeds of standard polymeric formula. Low-profile devices can be inserted initially using the single-stage procedure or after 2-3 months by replacing a standard PEG tube, in those requiring longer-term feeding. Having had a period of non-use and reliance upon oral intake for growth and weight gain-typically 8-12 weeks-a PEG may then safely be removed after due consultation. In the event of non-closure of the fistula the most successful method for closing it, to date, has been a surgical procedure, but the Over-The-Scope-Clip (OTSC) has recently been used with considerable success in this scenario. CONCLUSIONS: A multidisciplinary approach is mandatory for the best possible treatment of children with PEGs. Morbidity and mortality are minimized through team decisions on indications for insertion, adequate planning and preparation before the procedure, subsequent monitoring of patients, timing of the change to low-profile devices, management of any complications, and optimal timing of removal of the PEG.

International audience; Acute diarrhoea is a leading cause of morbidity and mortality in the paediatric population. Racecadotril is an antisecretory drug recommended as an adjuvant anti-diarrhoeal treatment.In the small bowel, the enzyme neutral endopeptidase (NEP) inhibits the action of enkephalins, which prevent water and electrolyte hypersecretion. By inhibiting NEP, racecadotril allows enkephalins to exhibit their antisecretory effects. Consequently, racecadotril reduces the secretion of water and electrolytes in the small intestine, without having an effect on intestinal motility. No serious adverse events related to racecadotril have been reported.Racecadotril has proven its efficacy as an adjuvant anti-diarrhoeal drug with a good safety profile. Its addition to oral rehydration solution (ORS) appears clinically beneficial and potentially leads to health care savings.

BACKGROUND: Anti-TNF drugs are effective treatments for the management of Crohn's disease but treatment failure is common. We aimed to identify clinical and pharmacokinetic factors that predict primary non-response at week 14 after starting treatment, non-remission at week 54, and adverse events leading to drug withdrawal. METHODS: The personalised anti-TNF therapy in Crohn's disease study (PANTS) is a prospective observational UK-wide study. We enrolled anti-TNF-naive patients (aged ≥6 years) with active luminal Crohn's disease at the time of first exposure to infliximab or adalimumab between March 7, 2013, and July 15, 2016. Patients were evaluated for 12 months or until drug withdrawal. Demographic data, smoking status, age at diagnosis, disease duration, location, and behaviour, previous medical and drug history, and previous Crohn's disease-related surgeries were recorded at baseline. At every visit, disease activity score, weight, therapy, and adverse events were recorded; drug and total anti-drug antibody concentrations were also measured. Treatment failure endpoints were primary non-response at week 14, non-remission at week 54, and adverse events leading to drug withdrawal. We used regression analyses to identify which factors were associated with treatment failure. FINDINGS:We enrolled 955 patients treated with infliximab (753 with originator; 202 with biosimilar) and 655 treated with adalimumab. Primary non-response occurred in 295 (23·8%, 95% CI 21·4-26·2) of 1241 patients who were assessable at week 14. Non-remission at week 54 occurred in 764 (63·1%, 60·3-65·8) of 1211 patients who were assessable, and adverse events curtailed treatment in 126 (7·8%, 6·6-9·2) of 1610 patients. In multivariable analysis, the only factor independently associated with primary non-response was low drug concentration at week 14 (infliximab: odds ratio 0·35 [95% CI 0·20-0·62], p=0·00038; adalimumab: 0·13 [0·06-0·28], p

OBJECTIVES The aim of the study was to assess differences in the diagnosis and management of eosinophilic esophagitis (EoE) by European pediatric (PG) and adult gastroenterologists (AG), and their self-reported adherence to guidelines. METHODS A multiple-choice questionnaire gauged the diagnostic and management strategies of gastroenterologists treating children or adults in 14 European countries and the United Arab Emirates (UAE). RESULTS Questionnaires were completed by 465 PG and 743 AG. PG were significantly more likely to take biopsies in patients with symptoms of esophageal dysfunction (86.2% PG vs 75.4% AG, P

Introduction: Paediatric Crohn’s disease (PCD) often presents with extensive and a frequent pan-enteric phenotype at onset. However, its long term evolution into adulthood, especially since the wid...

Background and AimsInflammatory bowel disease [IBD] is often one of the most devastating and debilitating chronic gastrointestinal disorders in children and adolescents. The main objectives here were to systematically review the incidence and prevalence of paediatric IBD across all 51 European states.MethodsWe undertook a systematic review and meta-analysis based on PubMed, CINAHL, the Cochrane Library, searches of reference lists, grey literature and websites, covering the period from 1970 to 2018.ResultsIncidence rates for both paediatric Crohn’s disease [CD] and ulcerative colitis [UC] were higher in northern Europe than in other European regions. There have been large increases in the incidence of both paediatric CD and UC over the last 50 years, which appear widespread across Europe. The largest increases for CD have been reported from Sweden, Wales, England, the Czech Republic, Denmark and Hungary, and for UC from the Czech Republic, Ireland, Sweden and Hungary. Incidence rates for paediatric CD have increased up to 9 or 10 per 100 000 population in parts of Europe, including Scandinavia, while rates for paediatric UC are often slightly lower than for CD. Prevalence reported for CD ranged from 8.2 per 100 000 to approximately 60 and, for UC, from 8.3 to approximately 30.ConclusionsThe incidence of paediatric IBD continues to increase throughout Europe. There is stronger evidence of a north–south than an east–west gradient in incidence across Europe. Further prospective studies are needed, preferably multinational and based on IBD registries, using standardized definitions, methodology and timescales.

BACKGROUND & AIMS: Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.METHODS: We performed a genome-wide association study to identify variants associated with time to development of anti-drug antibodies in a discovery cohort of 1240 biologic-naïve patients with Crohn's disease starting infliximab or adalimumab therapy. Immunogenicity was defined as an anti-drug antibody titer ≥10 AU/mL using a drug-tolerant enzyme-linked immunosorbent assay. Significant association signals were confirmed in a replication cohort of 178 patients with inflammatory bowel disease.RESULTS: The HLA-DQA1*05 allele, carried by approximately 40% of Europeans, significantly increased the rate of immunogenicity (hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.60-2.25; P = 5.88 × 10-13). The highest rates of immunogenicity, 92% at 1 year, were observed in patients treated with infliximab monotherapy who carried HLA-DQA1*05; conversely the lowest rates of immunogenicity, 10% at 1 year, were observed in patients treated with adalimumab combination therapy who did not carry HLA-DQA1*05. We confirmed this finding in the replication cohort (HR, 2.00; 95% CI, 1.35-2.98; P = 6.60 × 10-4). This association was consistent for patients treated with adalimumab (HR, 1.89; 95% CI, 1.32-2.70) or infliximab (HR, 1.92; 95% CI, 1.57-2.33), and for patients treated with anti-TNF therapy alone (HR, 1.75; 95% CI, 1.37-2.22) or in combination with an immunomodulator (HR, 2.01; 95% CI, 1.57-2.58).CONCLUSIONS: In an observational study, we found a genome-wide significant association between HLA-DQA1*05 and the development of antibodies against anti-TNF agents. A randomized controlled biomarker trial is required to determine whether pretreatment testing for HLA-DQA1*05 improves patient outcomes by helping physicians select anti-TNF and combination therapies. ClinicalTrials.gov ID: NCT03088449.

INTRODUCTION: \ud Thetanix (gastroresistant capsules containing lyophilized Bacteroides thetaiotaomicron) is a live biotherapeutic, under development for Crohn's disease, that antagonizes transcription factor nuclear factor kappa B, reducing proinflammatory cytokines, particularly tumor necrosis factor alpha. We aimed to assess safety and tolerability in adolescents with Crohn's disease in remission.\ud \ud METHODS: \ud Subjects who were 16–18 years with Crohn's in remission (weighted pediatric Crohn's disease activity index 99% in part B. Two subjects reported adverse events deemed related—one in part A with eructation, flatulence, and reflux; one in part B with dizziness, abdominal pain, and headache. No serious adverse events were reported. There was no significant change in median calprotectin across part B (87.8 [4.4–447] to 50.5 [5.3–572], P = 0.44 by the Fisher exact test in the active group). No significant differences were found in microbiota profiles, but diversity seemed to increase in treated subjects.\ud \ud DISCUSSION: \ud Thetanix, after single and multiple doses, was well tolerated. Although the numbers in this study were small, the safety profile seems good. Future studies should explore efficacy.

INTRODUCTION AND OBJECTIVES: The endoscopy Global Rating Scale (GRS) is a web-based self-assessment quality improvement (QI) tool that provides a framework for service improvement. Widespread use of the GRS in adult endoscopy services in the United Kingdom (UK) has led to a demonstrable improvement in quality. The adult GRS is not directly applicable to paediatric endoscopy services. The objective of this study is to develop and pilot a paediatric endoscopy Global Rating Scale (P-GRS) as a QI tool.METHODS: Members of the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) Endoscopy Working Group collaborated with the Joint Advisory Group on Gastrointestinal Endoscopy (JAG) to develop the P-GRS. After a period of consultation, this was piloted nationally at 9 centres and data were collected prospectively at 2 census points, May and December 2016.RESULTS: The P-GRS mirrors the adult GRS by dividing care into 4 domains and includes 19 standards with several measures that underpin the standards. Eight services completed the online P-GRS return in May 2016 and 6 in December 2016. All pilot sites identified areas that needed improvement and post-pilot reflected on the key challenges and developments. Several positive developments were reported by the pilot sites.CONCLUSIONS: The national pilot helped ensure that the P-GRS developed was relevant to the paediatric endoscopy services. The pilot demonstrated that even in the first year of engaging with this QI tool, services were starting to identify areas that needed improvement, share best practice documents, put in place QI plans, and support greater patient involvement in services.

INTRODUCTION The paediatric series of direct observation of procedural skills (DOPS) were introduced into the UK national endoscopy training curriculum in 2016, but lack validity evidence. We aimed to present validity evidence for paediatric colonoscopy DOPS and study competency development in a national trainee cohort. METHODS This prospective UK-wide study analysed formative paediatric colonoscopy DOPS which were submitted to the e-Portfolio between 2016 and 2018. Item, domain, and average DOPS scores were correlated with the overall DOPS rating to evidence internal structure validity. Overall DOPS ratings were compared over lifetime procedure count to demonstrate learning curves (discriminant validity). Consequential validity was founded on receiver operating characteristic curve analyses. RESULTS A total of 203 DOPS assessments were completed for 29 trainees from 11 UK training centres. Internal structure validity was provided through item-total correlation analyses. DOPS scores positively correlated with trainee seniority (P

ObjectiveTo evaluate quality of paediatric endoscopy training of Young members of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN).MethodsAn online questionnaire designed by the Young ESPGHAN Committee was sent to 125 Young ESPGHAN members between February 2014 and September 2015. The questionnaire comprised 32 questions addressing some general information of the participants and the structure of their paediatric gastroenterology, hepatology and nutrition programmes; procedural volume and terminal ileal intubation (TII) rate; supervision, assessments, participation in endoscopy courses and simulator training; and satisfaction with endoscopy training and self-perceived competency.ResultsOf 68 participants, 48 (71%) were enrolled in an official training programme. All alumni (n=31) were trained in endoscopy. They completed a median of 200 oesophagogastroduodenoscopies (OGDs) and 75 ileocolonoscopies (ICs) with a TII rate of >90% in 43%. There is a significant difference in numbers of ICs between the TII rate groups >90%, 50%–90% and ConclusionsDespite reaching the suggested procedural endoscopy volumes, a rather low TII rate of >90% calls for end-of-training certifications based on the achievement of milestones of competency.

Background and AimAcute severe colitis [ASC] is associated with significant morbidity in paediatric patients with ulcerative colitis [UC]. Most outcome studies in ASC since tumour necrosis factor alpha [TNFα] antagonists became available have focused on the first year after admission. The aim of this study was to characterise the longer-term outcomes of paediatric patients admitted with ASC.MethodsThis retrospective study was conducted in 25 centres across Europe and North America. Data on patients with UC aged ResultsOf the 141 patients admitted with ASC, 137 [97.1%] were treated with intravenous corticosteroids. Thirty-one [22.6%] patients were escalated to second-line therapy, mainly to infliximab. Sixteen patients [11.3%] underwent colectomy before discharge. Long-term follow-up showed colectomy-free rates were 71.3%, 66.4% and 63.6% at 1, 3 and 5 years after initial ASC admission, respectively, and were similar across different age groups. Sub-analysis of colectomy rates in patients with new-onset disease [42.5% of the cohort] yielded similar results. In a multivariate analysis, use of oral steroids in the 3 months before admission, erythrocyte sedimentation rate >70 mm/h, and albumin ConclusionsHigh colectomy rates were demonstrated in paediatric UC patients admitted with ASC. Additional studies are required to determine whether intensification of anti-TNFα treatment, close therapeutic drug monitoring, and use of new drugs alter this outcome.

OBJECTIVES Direct observation of procedural skills (DOPS) are competence-assessment tools in endoscopy. Formative paediatric gastroscopy DOPS were implemented into the UK curriculum in 2016 but lack validity evidence; we aimed to assess validity evidence using a recognised contemporary validity framework. METHODS We performed a prospective UK-wide analysis of formative paediatric gastroscopy DOPS submitted to the e-Portfolio over 1 year. Internal structure validity was assessed using interitem correlations between DOPS items, average domain, and skillset scores and with the overall competency rating. Overall competence scores and mean DOPS scores were compared by trainee seniority and procedure count (discriminative validity). Receiver operating characteristic curve analysis was performed to explore if DOPS scores could be used to delineate procedural competency (consequential validity). RESULTS A total of 157 DOPS assessments were completed by 20 trainers for 17 trainees. Strengths of correlations varied between DOPS components, with overall competency correlating most with technical-predominant items, domains and skillsets. Both the overall assessor's rating and mean DOPS scores increased with trainee seniority (P