Sa2039 Inpatient Bowel Prophylaxis With Sennosides and Docusate Combination Therapy Reduces the In-Hospital Incidence of Constipation in Heart Failure Patients: A Retrospective Cohort Analysis Kyle Staller, Hamed Khalili, Braden Kuo INTRODUCTION: Hospitalized patients suffer disproportionately from constipation during their stays, however little data exists to guide clinicians in prophylaxis against in-hospital constipation. We performed a retrospective, cohort analysis of patients admitted to a quater- nary care center with congestive heart failure (CHF) to determine the effects of inpatient bowel prophylaxis on inpatient constipation. METHODS: All patients admitted to a quaternary care center with the primary diagnosis of CHF or its equivalent in 2012 (n=802) were evaluated for use of a standing bowel regimen on admission. Constipation was defined as new laxative use after 24 hours of admission, which reflected patient/nursing request or provider judgment that laxation was needed. We chose to examine CHF hospitalizations because predictors of length of stay in this population have been well established in previous studies and constipa- tion tracks with longer stays. We incorporated these previously-validated predictors of length of stay in combination with known and proposed predictors of constipation to create a model for inpatient incidence of constipation. We used this model to examine the effects of in-house constipation prophylaxis on new constipation during admission via logistic regression with estimation of odds ratios and 95% confidence intervals. RESULTS: 802 admissions were examined with 10 admissions excluded because the patients underwent colonoscopy with bowel preparation during their hospitalization. The remaining 792 patients were included to form the final regression model which included demographics (56% male, 85% white, mean age of 75), in-hospital mortality (1%), comorbidities, home medications, admission lab values, bowel prophylaxis on admission, and inpatient medications with the potential to cause constipation. In-hospital constipation occurred in 28.8% of admissions, including 19.0% of patients receiving no bowel prophylaxis and 9.7% of patients receiving prophylaxis. Home laxative use conferred a significantly-increased risk of constipation com- pared to patients not using laxatives at home (OR 3.6, 95% CI 2.1-6.3) and patients with home laxative use who were placed on inpatient bowel prophylaxis had a significantly- decreased risk of constipation compared to those who were not given prophylaxis on admission (OR 0.24, 95% CI 0.12-0.47). The use of sennosides/docusate combination prophylaxis significantly decreased the risk of constipation (OR 0.32, 95% CI 0.10-0.99) while sennosides and docusate monotherapy had no effect. CONCLUSIONS: Constipation is a common complication of inpatient stays for CHF, but our data suggests the risk is highest for patients taking laxatives at home. The risk of in-hospital constipation could be mitigated by giving sennosides/docusate prophylactic therapy on admission—especially to patients with preexisting constipation. Sa2040 Role of Ethnicity in the Presentation, Evaluation, and Etiology of Severe Constipation Erin Toto, Kaartik Soota, Lucy A. Salieb, Erkanda Ikonomi, Zubair A. Malik, Frank K. Friedenberg, Henry P. Parkman Introduction: Patients with constipation are often referred for anorectal manometry (ARM) as part of an evaluation to identify dyssynergic defecation. Previous studies have identified factors associated with constipation including female gender, older age, BMI, and various ARM parameters. The purpose of this study was to examine if differences exist between ethnic groups for patients referred for evaluation of constipation. Methods: Cross-sectional study of patients referred for ARM for evaluation of severe constipation from 1/2011-9/ 2013. Prior to manometry, patients completed a questionnaire detailing their abdominal symptoms and stool pattern. We developed a composite constipation score summing the quality of bowel movements, severity of straining, incomplete evacuation, and frequency of digital disimpaction. Patients were categorized into IBS-C, functional constipation, or neither using Rome III criteria. Ethnic group was self-reported; our analysis was restricted to Non- Hispanic White (NHW), Non-Hispanic Black (NHB), and Hispanic patients. ARM was performed using a Medtronic Diagnostics water-perfused system. Results: 501 patients underwent ARM; mean age 45.9±16.9 years, 417 (83.2%) female, 399 (79.6%) NHW, 74 (14.8%) NHB, and 28 (5.6%) Hispanic. NHB patients were older (P=0.03) and had a higher BMI (P<0.001), especially compared to NHW. Duration of symptoms prior to testing tended to be longer for Hispanic patients (P=0.06). On ARM, the sensory threshold for rectal balloon distention was higher for Hispanics compared to NHW and NHB patients (P<0.001). Additionally, balloon expulsion time was delayed in Hispanics relative to NHW and NHB patients (P=0.03). Overall, there were 99 patients who met criteria for dyssynergic defecation, with no differences between the ethnic groups (P=0.26). The majority of NHW and NHB patients met criteria for IBS-C, higher than for Hispanic patients (P=0.001). Less NHW patients met criteria for functional constipation compared to NHB and Hispanic patients, although this was not significant (P=0.33). The only independent predictor of constipation severity was female gender (P=0.035). Conclusions: Of patients undergoing ARM for severe constipation, Hispanic patients experienced symptoms longest prior to referral, had higher sensory thresholds for balloon distension, and required more time to pass the balloon. Ethnicity, however, was not associated with composite symptom severity. NHW and NHB patients met criteria for IBS-C more often than Hispanic patients, but there was no significant difference between ethnic groups in terms of dyssynergic defecation or functional constipa- tion. These results show that manometric differences exist between ethnicities and the reason for constipation may also differ. Future research should investigate whether a differential response to therapy exists. Characteristics of patients by ethnic group S-361 AGA Abstracts *P<0.05 **P<0.01 Sa2041 RQ-00432933, a Novel Orally Active Small Molecule Ghrelin Receptor Agonist for Potential Use in Cancer Patients With Gastrointestinal Dysmotility and Anorexia/Cachexia Nobuyuki Takahashi, Keiko Obata, Makiko Kuroda, Akiko Yamada, Yasuhiro Iwata Background: Patients that use opioid analgesics often experience opioid-induced bowel dysfunction (OBD). The OBD comprises several symptoms including constipation, anorexia, nausea and vomiting, delayed digestion, citing negative impact on quality of life. Ghrelin and ghrelin mimetic stimulate appetite and enhance gastrointestinal (GI) motility in humans; it is a reasonable assumption to consider that ghrelin agonist can benefit both OBD and anorexia/cachexia cancer patients treated with opioids. In the present studies, we investigated the pharmacological profile of RQ-00432933 (RQ-933), a novel small molecule ghrelin agonist. Methods: In vitro functional activity of RQ-933 was evaluated in calcium influx assay using stable human ghrelin receptor/HEK293 cells. Growth hormone (GH) response; RQ-933 (1-10mg/kg) was administered orally to the female BALB/c mice after overnight fasting. Blood samples were collected at 5, 10, 30min after RQ-933 administration. Plasma concentrations of mouse GH were measured using EIA kit. Anabolic effect; RQ-933 (15, 30mg/kg) was administered orally to the female BALB/c mice at the end of light phase for 14 days, and body weight (BW) was monitored. Effect on bowel dysfunction in OBD model; after oral administration of RQ-933, loperamide was injected subcutaneously. Fifteen minutes after administration of loperamide, 5% (w/v) charcoal meal was orally administered. Thirty minutes after ingestion of charcoal meal, mice were euthanized and GI tract from the pylorus to the ileocecum was removed. The transit rate (%) of the length from the pylorus to the tip of the charcoal against the total length of the removed GI tract was measured. Results: The cell-based functional assay demonstrated that RQ-933 was potent agonist against the human ghrelin receptor with an EC50 value of about 7nM. The effect was comparable to the capromorelin (4nM) or anamorelin (12nM). RQ-933 and capromorelin increased plasma GH levels at 3mg/kg or more in in vivo. The plasma GH levels in response to RQ-933 (10mg/kg) peaked at 10min after dose and the concentration was 39.6ng/mL (mean, N=2). The plasma concentration of RQ-933 (10mg/kg) was 1085 ng/mL at 10min after dose. In animals administered RQ-933 at 15mg/kg showed a significantly higher BW gain at day 14 compared with vehicle-treated mice (p<0.01, 2.7+/-0.4g versus 0.9+/-0.2g, mean+/-SD, N= 6). Treatment of mice with loperamide significantly decreased small intestinal transit (SIT) by more than 40% compared with the vehicle control. Preliminary results indicated that oral administration of RQ-933 increases SIT. Conclusion: We developed RQ-933 which is orally active ghrelin receptor agonist. This drug is currently in the pre-clinical test phase. The results observed in vivo suggest that RQ-933 will be a useful therapeutic agent for GI dysmotility and anorexia/cachexia in cancer patients. Sa2042 Dependence of Colonic Motor Patterns on 5-HT3 and 5-HT4 Receptor Activation in the Rat Yuanjie Yu, Ji-Hong Chen, Xiaohui Du, Lu Hong, Hong Liao, Longyin Jiang, Hongfei Li, Zixian Yang, Junbo Shi, Xiangdong Yin, Jan D. Huizinga Serotonin is a critical neurotransmitter of the enteric nervous system affecting colonic motility, and drugs acting on 5-HT receptors are being developed to affect colonic dysmotility. To better link 5-HT related drugs to abnormal colonic motility we investigated the roles of 5- HT receptor agonists and antagonists on whole colon motility in rats. In the whole rat colon three major motor patterns have been described using spatiotemporal mapping: pan-colonic Long Distance Contractions (LDCs), ripples occurring prominently in the proximal colon, as well as Rhythmic Propulsive Motor Complexes (RPMCs) that occur primarily in the mid and distal colon. Our aim was to study 5-HT3 and 5-HT4 receptor involvement in all the motor patterns. Results: 5-HT3 antagonists (ondansetron, palonosetron and others) abolished LDCs except their most proximal part and they inhibited or enhanced RPMCs in the distal colon. m-CPBG , a selective 5-HT3 agonist (1-10 μM) showed dose dependent inhibition of LDCs and RPMCs. 5-HT4 agonists (mosapride, prucalopride) inhibited the length and frequency of LDCs but markedly promoted RPMCs in distal colon. The 5-HT4 antagonist GR125487 (120 nM) had an inhibitory effect on the LDCs and RPMCs. 5-HT (5-20 μM) strongly inhibited all activity. Ripples were largely unaffected by 5-HT compounds. Conclu- sions: LDCs and RPMCs are created by different neuronal programs, with LDCs dependent on 5-HT3 receptor activation and distal RPMC activity promoted by 5-HT4 receptor activation and inhibited by 5-HT4 receptor blockade. Hence 5-HT4 activation abolishes a pan-colonic propulsive activity (LDC) but promotes a different neurogenic propulsive motor pattern AGA Abstracts