Opiods and Cyclical Vomiting Syndrome

interrupted, acotiamide administration was resumed. RESULTS: A total of 412 patients were recruited, and 405 patients were included in Full Analysis Set (FAS). OTE improved in 73.2% of the 405 patients at the point of last evaluation. Symptomatic improvement and/ or completely resolution was observed in 10.9% of the 405 patients at the point of last evaluation. Cessation rate of acotiamide was 75.1%, remission rate was 38.0%. Only minor side effects were observed in this study, except that serious increased alanine aminotransferase was reported in one patient. CONCLUSION: Acotiamide is the safe and effective drug, which could lead FD patients to remission. Tu1359 Efficacy and Safety Study of Acotiamide (Z-338) in European Patients With Functional Dyspepsia Jan F. Tack, Vincenzo Stanghellini, Gerald Holtmann, Stanislas Bruley des Varannes, Alain Vandenberghe, Kohei Morooka, Eiichi Nagano, Hiroki Kato Background: Acotiamide is a novel gastroprokinetic drug which has shown the therapeutic potential in functional dyspepsia (FD) in studies in the US, Japan and Europe. These studies suggest that acotiamide is more effective in the Postprandial Distress Syndrome (PDS) compared to Epigastric Pain Syndrome (EPS) FD Rome III based subgroups. Aims: To evaluate the efficacy and safety of two doses of acotiamide on FD patients. Methods: Two hundred and eighty-nine FD patients, diagnosed according to ROME II criteria, were treated with acotiamide 100mg (n=96), 300mg (n=97) or placebo (n=96) TID for 12 weeks. The eligibility was assessed in a 2-week screening period before treatment, during which either postprandial fullness (PF) or early satiety (ES) (PDS symptoms) should be the most bothersome symptom, and with no more than mild heartburn. The primary efficacy was evaluated by a binary patient global question: Global Subject Outcome Assessment (GSOA), at Week 12. The secondary endpoints were weekly GSOA, 50% response rate of GSOA and the individual symptom score (5 Likert scale) of 5 dyspepsia symptoms (PF, ES, upper abdominal bloating, nausea and epigastric pain (EP)). In the post hoc analysis the same endpoints were examined in the sub-group of patients with a low EP mean score (<1.0) in the screening period. Results: GSOA at week 12, weekly GSOA, 50% responder rate of GSOA and individual symptom scores in PDS symptoms showed higher improvement in acotiamide treated groups compared to placebo, but these differences did not reach statistical significance. In contrast, in post hoc analysis marked improvements occurred in the acotiamide 100 mg groups, with significant differences in 50% response rate of GSOA (Week 1 to 12: p=0.042) and the individual symptom sore of PF (Week 7 to 12: p=0.020 to 0.048) and of ES (Week 9 to 12: p=0.036 to 0.048) compared to placebo. Conclusions: Acotiamide 100mg had significant efficacy on 50% responder rate of GSOA and PDS symptoms for FD patients with low EP.

Tu1357 Efficacy of Acotiamide (Z-338) in Patients With Postprandial Distress Syndrome or Overlap of Epigastric Pain Syndrome and Postprandial Distress Syndrome in Functional Dyspepsia Kei Matsueda, Michio Hongo, Jan F. Tack, Youichi Saito, Hiroki Kato BACKGROUNDS and AIM: The Rome III Committee defined two distinct sub-groups of Functional Dyspepsia (FD): Postprandial Distress Syndrome (PDS) and Epigastric Pain Syndrome (EPS), although substantial overlap exists. Recent randomized controlled trials of acotiamide in FD demonstrated symptomatic improvement in postprandial fullness (PF), and early satiation (ES), and upper abdominal bloating (UA), symptoms corresponding to PDS according to Rome III criteria (DDW2007). We therefore investigated the therapeutic efficacy of acotiamide on PDS or PDS+EPS by stratified analysis of patients' symptoms in a Phase III study in Japan. METHODS: FD patients according to Rome III criteria, with negative endoscopy and no heartburn, were randomized to acotiamide 100mg (n=452) or placebo (n=445) TID for 4 weeks. During a 1-week observation period, patients reporting PF, ES, or UA of at least moderate intensity on more than 2 days were eligible. Patients were reclassified by the severity of symptoms (EPS and PDS) based on baseline measurements. The primary endpoints of therapeutic efficacy at week 4 were assessed by patients-reported global assessment of Overall Treatment Efficacy (OTE) according to a symmetrical 7-point Likert scale and the elimination rate of 3 symptoms (PF, ES and UA) at week 4. Responder of OTE was defined by the upper two Likert items on the scale. RESULTS: 197 of the patients were classified into EPS+PDS, and 695 patients were classified into PDS. The results of the acotiamide and placebo groups are shown in tables. CONCLUSION: This study suggests that acotiamide (100mg TID) is effective for the treatment of patients with both PDS and PDS+EPS overlap in Functional Dyspepsia. OTE

(1): Response rate (%), (2): Change at Week12 from baseline (a)p=0.042, (b)p=0.026, (c) p=0.048

Elimination rate of 3 symptoms (PF, ES and UA)

Tu1360 Opiods and Cyclical Vomiting Syndrome Shreyas Saligram, Klaus Bielefeldt Background -Cyclical vomiting syndrome (CVS) is increasingly recognized in adults, with recent reports suggesting ‘coalescing attacks’ in up to one third of the patients. We hypothesized that the common need for analgesic treatment may contribute to coalescing attacks through development of opioid dependence and withdrawal, triggering and/or mimicking CVS. Methods-A retrospective review was performed to identify patients treated for CVS by a single physician between Jan and October of 2010. Demographic data, clinical presentation, treatment, cumulative opioid prescriptions and administration during hospitalizations and emergency room visits and days of inpatient stay were abstracted from the chart. Opioid use was expressed in morphine equivalents per month using published conversion factors. Results- Thirty patients (age 40.6±3.3 years; 73% female) were seen within this time frame with 23 patients being followed for at least 6 months (12.3±1.7 months). The average age at symptom onset was 31±3.5 years with a mean duration of episodes of 3.2±0.4 days and 0.9±0.2 month between attacks. Five patients had dysautonomia, 20 suffered from anxiety and/or depression, 12 had migraines. In univariate analyses, the best predictors of repeat hospitalizations were cumulative opioid dosage (r2=0.67), short interval between attacks (r2=0,46), a coexisting anxiety disorder (r2=0.44) and marijuana use (r2=0.4). Half of the patients were treated with tricyclic antidepressants, 14 patients received anticonvulsive agents. Eight patients accounted for 91% of the hospital days with all but one receiving high opioid dosages (monthly morphine equivalent of 520±180 mg). As shown in the figure, there was an increase of opioid use over the course of one year. Considering the high opioid dosages and the potential role of iatrogenic dependence, slow opioid tapering over 2-3 weeks was tried in these patients and led to a significant reduction in hospitalizations from 48.7±5 days to 15.5±8.2 days per year Conclusion: CVS is an increasingly recognized disorder with often dramatic clinical presentation. While opioid therapy plays an important

Tu1358 A Long-Term Study of Acotiamide in Patients With Functional Dyspepsia : Results From an Open-Labeled Phase III Trial in Japan on Safety and Efficacy Kei Matsueda, Michio Hongo, Satoshi Ushijima, Hiraku Akiho, Hiroki Kato INTRODUCTION: Acotiamide (Z-338) is a novel gastroprokinetic drug that exhibited therapeutic effects on gastric emptying and/or gastric accommodation in preclinical studies. In Randomized, Double-Blind, Placebo-Controlled Phase III trial, acotiamide improved mealrelated dyspeptic symptoms. Therefore, acotiamide is the first drug to demonstrate efficacy for Functional Dyspepsia (FD) under Rome III criteria. AIMS: To investigate the safety, efficacy of long-term acotiamide in FD patients. METHODS: FD patients compatible to Rome III criteria with negative endoscopy were included. Patients with heartburn were excluded. Those who had postprandial fullness (PF), upper abdominal bloating (UA), or early satiation (ES) as bothersome symptoms, with moderate or severe intensity and for 2 days or more during the baseline period (7 days) were eligible for following pharmacological study. Acotiamide 100mg TID were given to the patients for up to 48 weeks. Subjective symptoms of PF, UA and ES were evaluated by patients by means of 7-point Likert Scale from week 0 to week 8 during acotiamide administration. Patient-reported global assessment of overall therapeutic efficacy (OTE) was recorded every week during treatment period. If OTE was assessed as improved or improved significantly for 3 times or more in each month, acotiamide administration was abstained, and if this abstain lasted for 3 months, the patient was considered to have been under remission status and acotiamide was completely discontinued. If OTE was assessed as not improved twice or more in each month while acotiamide was

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AGA Abstracts

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calculated for all measurements. Results: COVs of all measured parameters are displayed in a table below. COV of % retention at 2h and 4h was much higher than COV of % of emptying at the same time both in H and GP. COVs of T50 and T90 were similar in H and GP. COV of GET was lower than COV of most GES parameters, being most close to T90 in H and GP. COV of GES reported as % of retained radioactive were extremely high, especially % retention at 4 hours. COV of GES % emptied were much lower despite the fact that the results express the same physiological event and are being calculated from the same data. Conclusions: Of all measurements, the COV of GET and T90 were most similar probably due to the close physiologic relationship between the events. Comparing WMC to GES results is best between T90 and GET. The COVs of 2 and 4 hour GES parameters can be skewed widely due to the bound nature of these later two parameters and the ceiling effect observed in the distribution of their normal data. Care must be taken when evaluating and comparing the performance characteristics of these tests results because the method of result reporting can dramatically affect the performance characteristics. Table 1. Coefficient of Variance of Gastric Emptying Results - by GES and WMC in Healthy and Gastroparetics

test, ultrasound, radiological tests, extensive laboratory work (including HBA1c) and careful clinical assessment were performed before patients received a final diagnosis. Results: Among the 125 patients presenting with N/V, 94(76.4%) were F and the mean age was 51. Sixty three (51%) were Hispanic, 58 (47%) were Caucasians and 4 (3.3%) were African Americans. The etiologies of N/V among all subjects were determined as follows: 25 (20%) had diabetic gastroparesis (GP), 15 (12%) idiopathic GP, 21 (17%) dumping syndrome, 17 (14%) cyclic vomiting, 6 (5%) conditioned vomiting, and 2 (1.6%) rumination. The comparison between Hispanics and Caucasians are summarized in Table 1. Conclusions: In a predominantly Hispanic population with N/V: 1) Hispanics had a higher frequency of diabetic GP when compared to Caucasians (29% vs 12%), while Caucasians dominated the idiopathic GP group (17% vs 8%); 2) Other than GP causes for N/V were more common in Caucasian (50% vs 20%). 3) Since the proportion of Hispanics throughout the USA is growing it's important to recognize the specific etiologies of nausea and vomiting in this population. Demographics and Etiologies

AGA Abstracts

role in management of acute episodes, ongoing opioid therapy is a poor prognostic marker and may lead to iatrogenic dependence and withdrawal. As even mild withdrawal symptoms may function as stressors and trigger CVS exacerbations, slow tapers should be considered to decrease the likelihood of repeat exacerbation.

Opioid use expressed in morphine equivalents per month Tu1361 Proton Pump Inhibitor Therapy Use Does Not Predispose to Small Intestinal Bacterial Overgrowth Shiva K. Ratuapli, Taylor G. Ellington, Mary O'Neill, Lucinda A. Harris, Amy E. FoxxOrenstein, George E. Burdick, John K. DiBaise, Michael D. Crowell Background: Small intestinal bacterial overgrowth (SIBO) occurs due to an increase or an alteration of the microbiota within the upper gastrointestinal tract. Hypochlorhydria from use of proton pump inhibitor therapy (PPI) has been suggested as a risk factor for developing SIBO. Studies have yielded conflicting results on the association between PPI therapy and risk of developing SIBO. Aim: To compare the prevalence of SIBO as measured by glucose hydrogen breath testing (GHBT) in patients on PPI therapy vs. those not on PPI therapy. Methods: A retrospective chart review was completed for all the patients who underwent GHBT testing from 2004 to 2010. Breath samples for hydrogen (H2) and methane (CH4) were collected prior to and every 20 mins for 120 mins following ingestion of a 50g oral glucose load. Gastrointestinal symptoms were assessed at baseline and over the 2 hour test period. Due to lack of universally accepted cut-off values for hydrogen and methane, we used following criteria for positive GHBT (a) H2 > 20 ppm b) H2 > 10 ppm c) CH4 > 15 ppm d) either H2 > 20 ppm or CH4 > 15 ppm. Patients with prior gastrointestinal surgeries were excluded. Demographic, clinical and PPI data were compared between the two groups using SPSS v18.0 (Chicago, IL). Results: The study included 1191 patients (70% female), of which 566 (48%) were on PPI therapy. A clinical diagnosis of IBS was found in 230 (19%) pts that were evenly distributed between PPI (44%) and non-PPI (56%) groups (P = 0.24). GHBT positivity did not differ significantly between PPI users and non-users by any of the diagnostic criteria used (Table). GHBT positivity was associated with older age (OR 1.02, 95% CI 1.01-1.04) and antidiarrheal use (OR 2.31. 95% CI 1.39-3.83) using H2 > 20, older age (OR 1.01, 95% CI 1.00 - 1.02) and diarrhea (OR 1.48, 95% CI 1.12-1.95) using H2 > 10, and older age (OR 1.01, 95% CI 1.00 - 1.02) and lower BMI (OR 1.03, 95% CI 1.01-1.06) using either H2 > 20 or CH4 > 15. PPI use was not significantly associated with GHBT positivity using any of these criteria. Conclusion: In this large patient sample, PPI use did not predispose to development of SIBO. Differences in sample size, patient characteristics and dietary intake might explain the observed variation in results from other studies. Prospective studies are needed to confirm these findings.

Tu1363 Cannabinoid Hyperemesis: A Case Series of 98 Patients Douglas A. Simonetto, Amy S. Oxentenko, Margot L. Herman, Jason Szostek Introduction: Cannabis is the most widely used illicit drug in the world. In 2004, chronic cannabis use was identified as a cause of cyclic vomiting, and the term Cannabinoid Hyperemesis (CH) was coined. Since then, several case reports have identified important clinical features of CH. Given the prevalence of cannabis use, the recent recognition of CH and the paucity of literature on CH, it is likely that this disease is significantly under-recognized. In order to promote wider recognition and further understanding of this condition, we conducted a case series, the largest to-date, of patients diagnosed with CH at our institution. Methods: Using institutional software, the electronic medical record was searched from January 1, 2005 through June 15, 2010. Patients were included if they had 1) chronic marijuana use prior to the start of symptoms, 2) a history of recurrent vomiting and 3) the absence of a major illness that could explain the symptoms. As a result, 1571 patients were identified, of which 98 met inclusion criteria. Results: The majority of patients were males (67%) with the average age of symptom onset at 25.3 ± 8.9 years. The majority (68%) consumed cannabis products for more than 2 years prior to symptoms, and 98% used it more than once per week. All patients had symptoms of cyclic nausea and vomiting. Eightyfour patients (86%) had associated abdominal pain; 61% described the pain as epigastric while 23% reported a periumbilical location. Fifty-seven patients had documentation of the effects of hot water bathing on their symptoms; of these, 91% reported relief of their symptoms with hot showers or baths. Diagnostic studies were obtained in most patients and were negative for alternative diagnoses. Follow-up was reported in only 10 patients (10%). Six patients stopped using cannabis and noted complete resolution of their symptoms. The time to improvement varied from 1 to 3 months. Discussion: Based on our patient data, we propose clinical criteria, divided into major and supportive features, for diagnosing CH. Chronic cannabis use is essential for the diagnosis. The major features include 1) severe cyclic nausea and vomiting, 2) resolution with cannabis cessation, 3) relief of symptoms with hot showers or baths, 4) abdominal pain and 5) weekly use of cannabis. The supportive features are 1) age less than 50, 2) weight loss of greater than 5 kg, 3) morning predominance of symptoms, 4) normal bowel habits and 5) negative diagnostic evaluation. CH should be considered in younger patients with chronic cannabis use and recurrent nausea, vomiting and abdominal pain. The timing, location and characteristic of symptoms can be helpful diagnostically, and patients should be asked about the relief of symptoms with hot water bathing. Cessation of cannabis use should result in improvement of symptoms.

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What Are the Most Common Etiologies of Nausea and Vomiting in a Predominantly Hispanic Population? Ana C. Zamora, Mithun Pattathan, Alicia Alvarez, Ricardo Badillo, Suhair Aldewairey, Richard McCallum, Irene Sarosiek

Factors Affecting Patient Outcome, Following Surgical Insertion of Gastric Electrical Stimulator for Gastroparesis - 10 Year Experience in a Single UK Centre Adriana Rotundo, Alan Askari, Francesco Pata, Cheuk Bong Tang, Mark AlexanderWilliams, Michael Harvey, Sritharan Kadirkamanathan

Introduction: There are a paucity of comprehensive studies highlighting the different etiologies of nausea/vomiting (N/V) among various racial/ethnic backgrounds and specifically in an Hispanic population. One of the gastrointestinal causes of N/V is gastroparesis (GP), a complication of longstanding diabetes mellitus which is highly prevalent among Hispanics. The objective of our study is to identify the most common etiologies of N/V in a predominantly Hispanic population in West Texas. Methods: Retrospective chart review of a 125 referred to a gastrointestinal (GI) motility clinic with a chief complaint of N/V. All patients were evaluated by one physician from October 2009 to October 2010. All relevant GI tests including upper endoscopy, colonoscopy, gastric emptying test (GET), four hour scintigraphy

AGA Abstracts

Background: Drug refractory gastroparesis is a debilitating disorder associated with severe nausea and vomiting, resulting in a negative impact on quality of life. High frequency gastric electrical stimulation (GES) is a viable, alternative treatment with a reported success rate of between 50 and 70%. This study looks at the factors affecting outcome that may help in improved patient selection. Patients and Methods: Clinical data from 48 patients with severe, intractable gastroparesis, (12 diabetic and 36 idiopathic) were studied. The median age of

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