AGA Abstracts 964 Agreement Between Deep Histological Remission and Mucosal Healing in Ulcerative Colitis and Predictors of Each Outcome Britt Christensen, Jonathan Erlich, Stephen B. Hanauer, David T. Rubin BACKGROUND: In patients with ulcerative colitis (UC), mucosal healing (MH) has emerged as a new therapeutic goal to prevent long-term complications. However a few small studies have demonstrated that MH may not always be an accurate indicator of histologic remission (HR). Presence of persistent microscopic inflammation may predict a higher risk of both colectomy and hospitalization in patients with UC and is associated with an increased risk of colorectal neoplasia. HR is therefore increasingly considered as an end-point in clinical trials. The aim of this study was to examine both the prevalence and possible predictors of MH, HR and MH without HR in patients with confirmed UC. METHODS: Patients with confirmed UC who had a baseline colonoscopy with biopsies taken in each segment of the colon (rectum, left-side and right-side) and had a follow-up colonoscopy more than one year later were identified. Each colonic segment of the final colonoscopy was evaluated retrospectively for MH as defined by the description of a normal mucosa or endoscopic quiescent inflammation and HR as defined by absence of residual histological inflammation. Demographic, clinical, histological and biochemical data were collected from case records. The primary outcome was MH, HR and MH without HR. Variables influencing HR, MH and MH without HR were examined using the chi-square test, Wilcoxon rank-sum test and logistic regression. RESULTS: 646 patients were identified; 60.0% had MH and 50.3% had HR. (Table 1) MH was strongly associated with HR (OR 13.41, 95%CI [7.137, 26.128], p<0.001). On multivariate analysis longer duration of disease (p=0.004), current therapy with an anti-TNF treatment (p=0.019), current therapy with an anti-metabolite (p=0.037) and C-reactive protein less than 3.0 (p=0.002) predicted MH. Predictors of HR on multivariate analysis were longer duration of disease (p=0.003), current therapy with an anti-TNF (p= 0.005), current therapy with an anti-metabolite (p=0.012), past therapy with steroids (p= 0.011) and C-reactive protein less than 3.0 (p<0.001). Of the 385 patients who had MH, 80 patients (20.8%) were found to have ongoing histological activity. On multivariate analysis only C-reactive protein more than 2.9 predicted ongoing histological activity in those with MH (AOR 3.56, 95%CI [1.55-8.16], p=0.003). CONCLUSION: MH is strongly associated with HR however 20.8% of patients with MH have evidence of histological activity on biopsy. C-reactive protein greater than 2.9 independently predicts ongoing histological activity in the presence of complete MH. These findings have considerable significance for evolving endpoints of management. Table 1: Baseline Characteristics 965 Efficacy and Safety of Prucalopride in Children With Functional Constipation: Results of a Multicenter, Placebo-Controlled, Phase 3 Trial Marc A. Benninga, Suzanne M. Mugie, Bartosz Korczowski, Alexandra Green, Jannie Ausma, Rene Kerstens, Magnus Ruth, Amy Levine Objectives: The aim of this multicenter, randomized, placebo-controlled, double-blind phase 3 trial (NCT01330381) was to evaluate the efficacy and safety of the 5-hydroxytryptamine type 4 (5-HT 4 ) receptor agonist prucalopride (PRU) in children with functional constipation aged ≥ 6 months to < 18 years. Methods: Children were enrolled based on the ROME III criteria for functional constipation. They received PRU (≤ 50kg: 0.04 mg/kg oral solution; > 50kg 2 mg tablet) or placebo (PLA) once daily for 8 weeks. The primary efficacy endpoint was the proportion of patients with an average of ≥ 3 spontaneous bowel movements (SBM) per week, and ≤ 1 fecal incontinence episode per 2 weeks in children who had acquired toileting skills, calculated over weeks 5-8 (responders). Endpoints were derived from daily e-diaries and questionnaires completed by children and parents. Health-related quality of life (HRQoL) was assessed with the PedsQL questionnaire, which uses a scale of 0-100, with higher scores indicating better HRQoL. Adverse events, clinical laboratory values, and electrocardiograms (ECGs) were monitored. Results: Efficacy and safety were assessed in 213 (107 PLA, 106 PRU) children. Their age distribution was: 25% < 4 years, 50% 4-< 12 years and 25% ≥ 12-< 18 years; 55.4% were female. Disease characteristics at screening were as follows: history of fecal incontinence - PRU: 62.3%, PLA: 55.1%; history of ≤ 1 SBM/week on average - PRU: 60.4%, PLA: 55.1%; severe/very severe constipation - PRU: 82.0%, PLA: 81.3%. The proportion of responders was similar in both treatment groups (PRU 17.0%; PLA 17.8%). No statistically significant difference in the primary efficacy endpoint was seen when stratified by sex, age group or country. No meaningful differences were observed between PRU and PLA in the secondary efficacy endpoints, including patients' satisfaction with treatment and their perception of disease severity. Overall improvements in PedsQL score from baseline to week 8 were similar in the prucalopride (child-report: +3.9 [SD: 13.8]; parent-report: +6.5 [SD: 13.9]) and placebo groups (child-report: +2.7 [SD: 12.4]; parent-report: +4.1 [SD: 14.2]). PedsQL subscale results showed no consistent changes. Overall, the incidence of treatment-emergent adverse events (TEAEs) was similar in the PRU (69.8%) and PLA groups (60.7%). The most common (> 10%) TEAEs in the PRU group were headache, pyrexia, abdominal pain and vomiting. There were no meaningful shifts in clinical chemistry, hematology, urine analysis or ECG parameters. Conclusions: In this study PRU was not more effective than PLA in children with functional constipation. PRU was generally well tolerated. S-172 AGA Abstracts 966 Gut Directed Hypnotherapy in Children With Irritable Bowel Syndrome or Functional Abdominal Pain: A Randomized Controlled Trial on Self Exercises At Home Using CD Versus Individual Therapy by Qualified Therapists Juliette M. Rutten, Arine M. Vlieger, Carla J. Frankenhuis, Elvira K. George, Michael Groeneweg, Obbe F. Norbruis, Walther Tjon a Ten, Herbert M. van Wering, Marc A. Benninga OBJECTIVES: Gut-directed hypnotherapy (HT) has been shown to be effective in children with irritable bowel syndrome (IBS) and functional abdominal pain (syndrome) (FAP(S)). It is however unavailable to many children, because HT is costly, requires a significant parental time investment and there is a shortage in qualified therapists. We conducted a multi-center RCT comparing the effectiveness of individual hypnotherapy by a therapist to home-based treatment using an audio CD with standardized hypnosis exercises. METHODS: These preliminary analyses include 234 children aged 8-18 years with IBS (n=117) or FAP(S) (n=117). Children were randomized to individual HT (n=115) or home-based HT with a CD (n=119). Individual HT was given by 12 different qualified therapists and consisted of 6 sessions over a 3-month period. Children in the CD-group were instructed to listen to the hypnosis CD, containing the same exercises used in the individual sessions, at least 5 times a week for a 3-month period. Pain frequency (PFS) and pain intensity (PIS) were measured using standardized abdominal pain diaries at baseline and after treatment. Treat- ment success was defined as a reduction in both pain frequency and intensity of at least 50%. Additionally, adequate relief was reported by parents. RESULTS: PFS scores decreased significantly from 15.0 to 6.5 in the HT-group (p=0.00) and from 14.6 to 9.1 in the CD- group (p=0.00). PIS scores in the HT-group decreased significantly from 15.1 to 6.9 (p= 0.00) and from 14.7 to 9.5 in the CD- group (p=0.00). However, reduction in PFS and PIS scores was significantly greater in the HT-group (p=0.02; p=0.01) compared to the CD group. In the HT-group 51.4% was successfully treated versus 36.8% in the CD-group (p= 0.03). There was a trend towards a higher percentage of adequate relief in the HT-group (82.1% vs. 71.3%; p=0.07). CONCLUSION: These preliminary analyses show that short term efficacy of gut-directed HT performed by different qualified therapists is superior to home-based treatment with a hypnosis CD with respect to pain frequency and intensity scores. Nevertheless, home-based treatment seems to be a valuable treatment option, given the high percentage of parents reporting adequate relief. 967 The Impact of Full Column, Non-Acid Reflux on Oropharyngeal Flora and Its Implications for Acid Suppression Use Rachel L. Rosen, Janine Amirault, Lan Hu, Doyle V. Ward, Melanie Baskind, Samuel Nurko Background: We have previously shown that full column, non-acid reflux burden is highly associated with positive bronchoalveolar lavage (BAL) cultures. We have further shown that, when non-acid reflux is further increased with acid suppression, additional changes in gastric and lung microflora ensue. Whether lung microflora changes are a result of direct microaspiration of bacteria-laden gastric fluid and/or a result of aspiration of oropharyngeal contents altered by full column reflux is unknown. It is the goal of this study: (1) to determine the relationship between full column, non-acid reflux and oropharyngeal microflora, and (2) to determine the impact of acid suppression, as a potentiator of non-acid reflux, on oropharyngeal microflora. Methods: We performed 16S deep sequencing on paired gastric fluid and oropharyngeal secretions from 116 children (57 off acid suppression therapy and 59 patients on therapy) who were undergoing endoscopy for the evaluation of respiratory symptoms. 50 patients also underwent pH-MII testing at the time of endoscopy. We compared differences in prevalence and relative abundance of bacteria genera in the gastric and oropharyngeal flora by creating prevalence ratios and performing Metastats analyses. We created correlation matrices between continuous reflux variables and bacterial abundance. Results: Between gastric/ oropharyngeal paired samples, there was overlap of 15 of the most prevalent bacterial genera identified. An abnormal total reflux burden by MII was associated with increased concentrations of Chryseobacterium (p=0.01), Cloacibacterium (p=0.004), Fuso- bacterium (p=.03) and Neisseria (p=0.02) in the oropharynx, the latter two of which are known causes of pharyngitis and upper respiratory tract infections. Furthermore, there were significant correlations between the percentage of full column reflux episodes and oropharyngeal concentrations of Fusobacterium (p=0.02), Neisseria (p=0.009), and Porphyro- monas (p=0.03), the latter of which is a know cause of dental disease. Full column, non- acid reflux specifically was correlated with concentrations of Neisseria (p=0.04). Recognizing that acid suppression increases non-acid reflux burden, we then compared the oropharyngeal flora of patients on and off acid suppression therapy. We found, in patients taking acid suppression, that there was an increased prevalence of Butyrivibrio (OR: 8.0, p=0.02), a bacteria previously identified in the BAL and gastric fluid of patients taking acid suppression. Conclusions: There is exchange of bacteria between the oropharynx and gastric environ- ments. One mechanism for this exchange may be full column reflux which, in our study, correlates with a greater abundance of specific oropharyngeal bacteria. Our data may provide a mechanism by which acid suppression causes infections and by which reflux causes dental disease. 968 Applying the Chicago Classification to a Pediatric Cohort: The Effects of Patient Age and Size on the Diagnosis of Esophageal Motility Disorders in Children Maartje Singendonk, Stamatiki Kritas, Charles Cock, Lara Ferris, Lisa McCall, Nathalie Rommel, Michiel P. van Wijk, Marc A. Benninga, David Moore, Taher Omari Background: Esophageal pressure topography (EPT) based diagnosis of esophageal motility disorders is rapidly becoming routine pediatric clinical practice. The classification of pediatric esophageal motor disorders based on the 2012 Chicago classification is however problematic