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sSu2014

Pain and Disease State in Pediatric Crohn's Disease: Impact on OutcomesMiranda A. Van Tilburg, Robyn Claar, Bisher Abdullah, Dalia Sherif, William E.Whitehead, Rona Levy

Introduction For pediatric patients with Crohn's disease, inflammation causes symptomssuch as pain, bloating and diarrhea. However, some patients report more symptoms thanothers, and symptom reporting may not coincide with disease state. This study sought toassess how common it is for patients to report pain levels that do not coincide with theirdisease state and how this impacts outcomes. Methods Participants included 112 children ages8-18 (57.1% boys, 85.7% Caucasian, mean age 13.9) with Crohn's disease who completedthe Faces Pain Rating, Functional Disability Inventory, Children's Somatization Inventory,Children's Depression Inventory, Multidimensional Anxiety scale, Pain Response Inventory,and Pediatric QoL Inventory. Physicians completed the Pediatric Crohn's Disease ActivityIndex to assess disease activity (flare vs remission). Results. Compared to remission (N=77),patients in a flare (N=35) had greater disability (M=.63 vs .32, p ,.001), somatic symptoms(M=.85 vs .61, p,.05), passive coping (M= 1.06 vs .75, p,.05), and anxiety (M=46.83 vs39.28 p,.001) as well as reduced quality of life (M=75.53 vs 82.26, p ,.001). There wereno group differences in depression by disease state. Next we dichotomized the sample into4 groups by pain (present or absent) and disease state (remission or flare). Most childrenreported pain concordant with their disease state (68.7%). Girls in a flare were more likelyto experience pain (66.7%) compared to boys (25%); no other differences were found bygender, age or race for the four groups. We examined those children whose pain does notcoincide with their disease state. Absence of pain during a flare (77.8% of those in a flare)was more common than reporting of pain during remission (48.6% of those in remission,p,.02). Reporting of pain while in remission was associated with increased disability (M=.71 pain vs M=.21 no-pain; p,.01), somatic symptoms (M=1.11 vs .45; p ,.01), anddepression (M=9.8 vs 6.0; p,.05) and decreased quality of life (M=72.8 vs 85.1; p ,.01).Absence of pain during a flare was associated with decreased disability (M=.45 no-pain vs.95 pain; p,.05), depression (M=6.2 vs 13.9; p,.001), and passive coping (M=.73 vs 1.52;p,.01) and increased quality of life (M=79.0 vs 61.6; p ,.01). No group differences werefound for anxiety. Conclusion Most pediatric patients with Crohn's disease report painconcordant with their disease state. When pain reporting is discordant with disease state,under reporting is more common than over reporting. The report of pain is associated withincreased depression, passive coping, and functional disability, and reduced quality of life.Pain reporting in Crohn's appears to be associated with both physical and psychological state.

Su2015

Prospective Randomized Trial of a Progressive Pediatric to Adult Transition ofCare Program in Adolescents With Inflammatory Bowel DiseaseDedrick E. Moulton, Michael J. Rosen, Dawn B. Beaulieu, Sara N. Horst, David A.Schwartz

BACKGROUND & AIMS: When an adolescent with inflammatory bowel disease (IBD)transfers care from the pediatric to adult gastroenterologist (GI), the shift from family- topatient-centered care, and new expectations for independence can be overwhelming. Whilevarious care models have been proposed to ease the transition process, their effectivenessis not known. The aim of this study was to determine whether a progressive transition programreduces hospitalization and disease exacerbation rates, and improves patient knowledge andsatisfaction. METHODS: Subjects ≥ 16 years old were randomized to progressive transition(PT) or standard transition (ST). For ST subjects, an appointment was scheduled with anadult GI within 3 months of their final pediatric GI visit. In the PT group, subjects completed3 transition visits at 3-month intervals. Visit 1: pediatric GI alone. Visit 2: combined visitwith the pediatric and adult GI, led by the pediatric GI. Visit 3: combined visit, led by theadult GI. At each visit, subjects were seen without parents, and knowledge of medicationnames, doses, side effects, monitoring, and insurance provider was assessed. After transition,patients were followed for up to 12 months, and hospitalizations, and instances of therapyescalations were recorded. Subjects rated their satisfaction with the transition process on a10-point scale. RESULTS: 40 subjects were randomized (19 PT, 21 ST). 6 PT subjects(31.6%) and 2 ST subjects (9.5%) were withdrawn from the study (P=0.089); primarily dueto failure complete transition. Of the remaining 32 subjects (13 PT, 19 ST), mean age was18 (range 16-21) years and 37.5% were female. Mean disease duration was 74 months(range 2-148 months). 90.6% were diagnosed with Crohn's disease and 9.4% with ulcerativecolitis. Baseline characteristics were similar between groups. Mean length of follow-up was223±107 days and 232±110 days in the PT and ST groups, respectively. At completion oftransition, 100% of PT subjects knew their medication names, doses, side effects, monitoringrequirements, and insurance provider, compared to 71% of ST subjects (P=0.18). Duringfollow-up, hospitalization for IBD occurred in 15.4% of PT subjects and 10.5% of ST subjects(P=0.7). Increased disease activity, as evidenced by escalation of medical therapy, occurredin 53.8% of PT subjects and 47.4% of ST subjects (P=0.7). 55% of PT subjects rated theirsatisfaction with transition as 10 out of 10 compared to 35% of ST subjects (P=0.3).CONCLUSIONS: A progressive transition program did not impact rates of hospitalizationsor disease exacerbations in this study. The requirement for a period of frequent follow-upin a progressive transition program was a challenge in this patient population. Progressivetransition from pediatric to adult IBD providers may result in improved patient knowledgeand satisfaction.

Su2016

Nutritional Therapy Modulates Inflammation and Improves Altered BarrierFunction in a Mouse Model of ColitisLily Nahidi, Steven T. Leach, Hazel M. Mitchell, Nadeem O. Kaakoush, Daniel A.Lemberg, John Munday, Karina Huinao, Andrew S. Day

Background: Exclusive enteral nutrition (EEN) is a well-established approach to the manage-ment of patients with active Crohn's disease (CD). However, the mode of action of EEN inpromoting mucosal healing is unknown. The aim of this study was to determine the effects

S-532AGA Abstracts

of EEN, in contrast with non-nutritional therapies, upon inflammation and barrier functionin a mouse model of colitis. Methods: Six-to-eight week old specific-pathogen-free interleu-kin-10-deficient (IL-10-/-) mice on a C57BL/6 background were challenged with a single doseof Helicobacter trogontum. Infected-mice were then treated with either EEN, metronidazole,hydrocortisone, or a combination of EEN and metronidazole. Two and four weeks afterinitiation of the treatments tissue was collected with histology, mucosal and tight junctionintegrity, inflammation and H. trogontum load assessed. Results: IL-10-/- mice infectedwith H. trogontum developed moderate-to-severe typhlo-colitis with acute-on-chronic tissuedamage. Typhlo-colitis was associated with intestinal barrier dysfunction as evidenced by asignificant elevation in short-circuit current, mucosal-to-serosal permeability flux to horserad-ish peroxidase, mucosal IL-8 and myosin light chain kinase mRNA levels, but decrease intrans-epithelial electrical resistance and tight junction structural proteins gene expression(P,0.05). Administration of EEN and metronidazole, but not hydrocortisone, in the infectedmice led to complete recovery of impaired intestinal barrier structure and function, resolutionof mucosal inflammatory events along with reduction in H. trogontum load (P ,0.05).Conclusion: H. trogontum infection in IL-10-/- mice induced typhlo-colitis with intestinalbarrier dysfunction. EEN and metronidazole treatments had significant and similar efficacyin modulation of gut barrier dysfunction and reversal of inflammatory changes, whereas,hydrocortisone only partially maintained barrier integrity and function. EEN likely promotesmucosal healing in CD by reducing bacterial load, reducing inflammation and promotingtight junction structural integrity.

Su2017

Impact of Chronic Constipation Severity on the Risk of Developing ColorectalCancer and Benign NeoplasmAnnie Guérin, Reema Mody, Beverly Fok, Eric Q. Wu, Karen Lasch, Nicholas J. Talley

Background: An association between chronic constipation (CC) and both colorectal cancer(CRC) and benign neoplasm has been demonstrated. However, little is known about theimpact of CC severity on the incremental risk of CRC and benign neoplasm. Objective: Toestimate the impact of CC severity on the risk of developing CRC or benign neoplasm.Methods: Patients with CC (≥2 diagnoses [Dx] of constipation [ICD-9-CM: 564.0x] between60 to 365 days apart) were identified from a large retrospective US claims database (Jan1999-Sep2011). Patients with Dx of irritable bowel syndrome or diarrhea were excluded. Patientswere required to be continuously enrolled in their health plan for ≥1 year following theindex date, which was patients' first eligible Dx of constipation. Patients were ≥18 of ageand free of CRC or benign neoplasm at the index date. The study period spanned from theindex date to the end of patients' continuous enrollment or a Dx of CRC or benign neoplasm.The following indicators of severity were measured over the one year following the indexdate: 1) ≥2 CC-related office visits, 2) a CC-related medical procedure (e.g., fecal disimpac-tion, pulse irrigation, colectomy, colon transit time test), 3) a gastrointestinal (GI) specialistvisit, 4) a prescription (Rx) fill for a laxative. Based on the number of indicators over theobservation periods, patients were stratified as mild (no indicator), severe (1 indicator), andvery severe (two or more indicators). Each CC patient was matched 1:3 to CC-free patientsby year of birth, sex, and region of residence. CC-free patients were patients who had neverbeen diagnosed for constipation and never had an Rx filled for a laxative during the entireobservation period. CRC and benign neoplasm were defined as ≥1 Dx for CRC or colorectalbenign neoplasm. Multivariate Poisson regression models were used to determine the relativeincidence of developing CRC or benign neoplasm for CC-free patients (reference) vs. CCpatients stratified by severity (mild, severe, very severe). Multivariate Poisson regressionmodels adjusted for age, sex, prevalent comorbidities, and family history of malignancy.Results: On average, CC (N=28,854) and CC-free (N=86,562) patients were 61.9 years oldand 33.3% male. Compared to CC-free patients, the adjusted incidence of developing CRCwas significantly higher in severe and very severe patients. Each level of CC severity wasassociated with an incremental risk of developing benign neoplasms. Conclusion: In a large,retrospective, US claims database, the risk of developing CRC and benign neoplasms overtime increased with the level of CC severity.

* Significant at the 5% level.

Su2018

Presentation of Abdominal Attacks of Hereditary Angioedema: What theGastroenterologist Should KnowEitan Rubinstein, Athos Bousvaros, Leslie E. Stolz, Christopher Stevens

Introduction: Hereditary angioedema (HAE) is a rare genetic disorder that results in unpre-dictable and acute attacks of subcutaneous or submucosal angioedema. More than 90% ofpatients have reported recurrent abdominal attacks that are characterized by abdominalpain, nausea, vomiting, and/or diarrhea. To better define the presenting symptoms of HAEabdominal attacks, we have analyzed data related to gastrointestinal symptoms at baselinein HAE patients enrolled in clinical trials of ecallantide, a plasma kallikrein inhibitor indicatedfor treatment of HAE attacks. Methods: The ecallantide clinical development program for