Su1129 Optimal Omeprazole Dosing and Symptom Control - A Randomized Controlled Trial (OSCAR Trial)

1 year. Fluid restriction was recommended in 19%, position changes were prescribed in 4%, fundoplication was performed in 2%, and 43% received gastrostomy. Comparisons between the severity of ARI in relation to demographic and aerodigestive clinical characteristics are shown (Table 1). CONCLUSIONS: Despite the use of pH-impedance testing technology to aid in the diagnosis of GERD, physicians continue to vary with differences in prescribing frequency of PPI as well as of its duration of use among complex neonatal ICU survivors. ARI severity predisposes to chronic PPI prescription and duration of use. Further research is needed with reliability of GERD specific symptoms and testing methods, dissemination of knowledge among pediatric medical care providers, and parental anticipatory guidance. Evaluation and consideration for alternative diagnosis and mechanisms that masquerade GERD-type of symptoms are needed. *Supported in part by RO1 DK068158 (Jadcherla) Table 1. Demographic, outcomes, and physician practice attitudes stratified by acid reflux index (ARI)

In Vitro Topical Protection of Human Esophageal Mucosal Integrity by Natural Products From the Northeast Region of Brazil Francisco Batista de Lima, Lucas Nicolau, Philip Woodland, Chung Lee, Ana Paula M. Santana, Durcilene Silva, José Roberto Leite, Isabele Melo, Miguel Angelo N. Souza, Armenio Aguiar Santos, Marcellus H. Souza, Daniel Sifrim Introduction: Myracrodruon urundeuva (MU) and Anacardium occidentale L. (AOL) (cashew) are natural products obtained from bark of Brazilian northeastern trees. They have previously shown gastro-protective effect in animal models of NSAID-induced inflammation. Impairment of esophageal mucosal integrity is important in the pathophysiology of GERD. Previous studies showed esophageal topical protective effect by alginates. We aimed to assess the mucosal protection effect of MU and AOL in human esophageal biopsies. Methods: Studies were performed on distal esophageal biopsies from 12 patients with heartburn (9 with NERD). Biopsies were mounted in specially adapted Ussing chambers to measure transepithelial electrical resistance (TER). After a 30 minutes period of stabilization, the chambers were opened for a short exposure of the biopsies' mucosal side to a "protectant solution". Negative control biopsies were not exposed to "protectants". Positive control biopsies were exposed to a commercial alginate based product. Protectant solution tested were: 1) hydroalcoholic extract of MU, solubilized in carboxymethylcellulose 2%; 2) gum obtained from AOL (cashew), solubilized in Krebs with 2.5% concentration and 3) gum obtained from AOL, solubilized in Krebs with 5% concentration. After washing the "protectant solution", the mucosal side of the biopsy was exposed to Krebs solution at pH 2.0 containing pepsin 1mg/mL and taurodeoxycholic acid 2mM. The following 30 minutes were recorded and the % change of TER was calculated. This study was approved by Local Ethics Committee (Federal University of Ceara 39538814.6.0000.5045). Results: The acid-pepsin-BA solution provoked a TER drop in the "unprotected" biopsies (negative control) of 20.02±2.4%. In biopsies protected by alginates (positive control), the TER drop was of 1.3±6.1 (P<0.05). The MU extract did not demonstrated protective effect (TER drop of 17.82±8.9%). The AOL cashew gum at 2.5% did not prevent a drop of TER. In contrast, AOL cashew gum at 5% had a significant (P<0.05) protective effect (TER drop of 1.69±2.4%). Conclusion: The AOL cashew gum 5% solution produced "in vitro" topical esophageal mucosal protection. This effect was probably due to its muco-adhesiveness properties provided by complex polysaccharides. In vivo long-lasting effect of this muco-protective product will be further explored as add-on therapy for GERD.

*P<0.05 vs ARI >7, †P<0.05 vs ARI 3-7, NCPAP-nasal continuous positive airway pressure, NC- nasal cannula

Su1129 Optimal Omeprazole Dosing and Symptom Control - A Randomized Controlled Trial (OSCAR Trial) Abhijeet Waghray, Nisheet Waghray, Adam T. Perzynski, M. M. Wolfe Introduction: Proton pump inhibitors (PPIs) are potent inhibitors of gastric acid secretion and comprise the mainstay of therapy for persistent gastroesophageal reflux disease (GERD). For optimal benefit, however, PPIs should be taken 30 min before the first daily meal and, if necessary, prior to the evening meal. Nevertheless, a recent survey found that only onethird of patients reported adherence to an optimal dosing regimen. Aim: This study was directed to determine whether patients with persistent GERD symptoms on suboptimal omeprazole dosing experience improvements in symptoms when randomized to an optimal dosing regimen. Methods: Patients with heartburn symptoms ‡3 times/week treated with omeprazole 20 mg were enrolled and observed for 2 weeks on their current regimen. They were then randomized to optimal dosing ( n=21) or continued suboptimal dosing ( n=31) of omeprazole for 4 weeks. Patients randomized to optimal dosing completed the study, while the remaining patients were further randomized to optimal ( n=18) or continued suboptimal (n=13) dosing for an additional 4 weeks. The primary endpoints were changes in symptom, frequency, and severity, as determined using the Gastroesophageal Reflux Disease Symptom Assessment Scale (GSAS) at 6 and 10 weeks. Baseline descriptive statistics were calculated and compared between the 2 study arms. GSAS composite measures were created, and Student's t-test and multivariate analysis of variance were used to analyze the effect of the intervention.Results: In total, 49 patients completed the study; 3 patients terminated their participation for unrelated medical issues. The average age of patients enrolled was 50.3 (SD=12.7) with 50% of patients taking omeprazole according to their personal preference (N=26). Baseline demographics revealed no significant difference between the two groups (Table 1). At 6 weeks, the optimal dosing arm showed significant improvement in GSAS symptom (5.11±2.21SD), frequency (1.00±0.69SD), and severity (0.46±0.34SD) scores (P<0.001 for each category) compared to the control arm GSAS symptom (8.73±3.04SD), frequency (2.23±1.34SD), and severity (1.05±0.59SD). The control group was further randomized to an optimal dosing strategy after week 6 ( N=18), and also experienced a reduction in GSAS symptom (6.28±2.93SD), frequency (1.34±0.89SD), and severity scores (0.72±0.48SD) at week 10 compared to those who maintained on their suboptimal regimen (N=12); symptom (7.97±3.15SD), frequency (2.27±1.45SD), and severity (0.87±0.64SD),

Su1128 How Do Treating Physicians Perceive GERD Among High-Risk Complex MultiSystemic Illness Among Neonatal ICU Infants Born Prematurely? Sudarshan Jadcherla, Swetha Sitaram, Kathryn Hasenstab, Lai Wei BACKGROUND: Gastroesophageal reflux disease (GERD) diagnosis rates vary from 2-30% in hospitalized premature neonates across the USA and results in 1-additional month of hospitalization, costing over $70,000 per neonate. Empiric usage of proton pump inhibitor (PPI) acid suppressive therapy in Neonatal ICU graduates varies widely. This has been attributed to lack of adequate screening tools or diagnostic methods. However the impact of esophageal acid reflux index (ARI) results from diagnostic testing on short-term and longterm physician prescription and management practice patterns is not known among neonatal ICU graduates. AIMS: To characterize the physician practice attitudes of managing GERD using pharmacological and non-pharmacological treatments among those NICU infants evaluated with pH-impedance studies stratified by the severity of ARI. METHODS: 100 infants (46 male) underwent diagnostic testing using pH-impedance methods for suspicion of GERD. We analyzed esophageal ARI and classified using NASPGHAN criteria of normal (ARI < 3), indeterminate (3 £ ARI £ 7), and abnormal (ARI > 7). Variables included: a) medication use, b) fluid restriction, c) position changes, d) fundoplication, and e) gastrostomy. Data presented as mean± SE, median (IQR), or %. Comparisons were made between GERD determinations of ARI stratifications and analyzed using ANOVA, Wilcoxon ranksum and Chi-squared tests. RESULTS: Subjects (29.8 ± 4.8 wks gestation, 1.5 ± 0.9 kg birth weight) were evaluated 44.2 ± 5.4 wks postmenstrual age (3.9 ± 0.1 kg) with ARI score 4.4(0.0 - 35.4). Overall, a) 60% were prescribed acid suppressive medication with PPI being the most frequent among 98%. Out of available data, 40 out of 52 (77%) subjects remained on PPI after 3 months, 30 out of 48 (63%) remained on PPI after 6 months, 21 out of 43 (49%) remained on PPI after 9 months, 13 out of 37 (35%) remained on PPI at

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recurrent cough improved from 40% (6 patients) preoperatively to 10% after 6 months (1 patient). One patient reported severe dysphagia pre-op that was resolved post-op. There was no change in the rate of occasional dysphagia reported. All patients were on long-term PPI at baseline. At 6 months, 17 (80%) patients were completely free of PPI use, 3 patients (8%) used PPI occasionally and only 5 patients (13%) were still taking daily PPI. Final safety data being analyzed and adjudicated by independent DSMB and will be reported at the meeting. Conclusions: In routine clinical practice, LES-ES is safe and effective in treating GERD patients with disruptive GERD symptoms despite PPI with improvement across all reported outcomes. LES-ES may be considered a viable treatment option for this indication.

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respectively. Conclusion: Patients who were administered a brief intervention to promote optimal PPI adherence demonstrated significant overall symptom improvement compared to those with continued suboptimal dosing. Proper education and PPI dosing should serve to reduce the burden of persistent GERD symptoms and related healthcare costs of uncontrolled disease.

Su1132 Efficacy of Hangeshashinto on Gastrointestinal Symptoms in Patients With Gastroesophageal Reflux Disease Refractory to Proton Pump Inhibitor Therapy Toshihisa Takeuchi, Shinpei Kawaguchi, Yoshiaki Takahashi, Satoshi Harada, Kazuhiro Ota, Yuichi Kojima, Kazuhide Higuchi [Background] It was shown that rikkunshito (RKT) combined with the standard-dose rabeprazole (RPZ) improved gastroesophageal reflux disease (GERD) symptoms in patients with PPI-refractory GERD, similar to the effects seen in treatment with a double dose of RPZ in a randomized, parallel comparative study. Though Japanese herbal medicine, hangeshashinto (HST) is used widely like RKT in Japan, HST and RKT have a different pharmacological characteristic. Numerous reports indicate that active ingredients of HST inhibit prostaglandin E2 production and/or the cyclooxygenase-2 expression. This strongly suggests that one of the therapeutic effects of HST is anti-inflammatory action. In addition, HST is used to treat upper gastrointestinal disorder (dyspepsia, heartburn, belch, etc) for its prokinetic activity. However, the effects of HST on upper gastrointestinal disorder have not been fully elucidated thus far. We investigated the efficacy of HST on gastrointestinal symptoms in GERD patient refractory to proton pump inhibitor (PPI). [Methods] This study was conducted as a prospective, multi-institution, open-label study. Patients with PPI-refractory GERD ( ‡Grade M) were defined as those with persistent GERD symptoms [frequency scale for the symptoms of GERD (FSSG) score ‡8] who are not responding to the standard PPI therapy for ‡8 weeks. Thirty PPI-refractory GERD patients received HST combination therapy [HST (7.5 g/day) with a standard dose of RPZ (10 mg/day)] for 4 weeks. Efficacy of HST was assessed by the comparison of FSSG scores before (baseline) and after treatments. Furthermore, features regarding HST efficacy were examined with respect to gender (man, female). [Results] The total FSSG score significantly decreased after 4 weeks of HST combination therapy compared to the baseline (baseline: 17.7±6.8, 4w:9.7±4.9, p<0.001). Moreover, the HST combination therapy significantly improved reflux symptom (RS) score and acid-related dysmotility (ARD) score and after 4 weeks. The improvement degree of the ARD scores of FSSG after 4 weeks of HST combination therapy was significantly higher in female patients than in male patients, i.e. among 12 subscale scores, HST was effective in "bloating sensation," "heavy feeling in stomach after meals," and "belch" in male patients. In some cases, HST improved diarrhea and QOL in PPI-refractory GERD patients with irritable bowel syndrome. [Conclusion] Our study demonstrated that the PPI combined HST therapy may be effective for the improvement of gastrointestinal symptoms in PPI-refractory GERD patients. Though HST may be effective in male patients with ARD symptoms, further investigations are required to clarify the characteristics of patients who respond to HST.

Su1130 Effect of Electrical Stimulation Therapy of the Lower Esophageal Sphincter on Postprandial Reflux Mechanisms in GERD Patients Nicolaas F. Rinsma, Boudewijn F. Kessing, Nicole D. Bouvy, Mark I. van Berge Henegouwen, Andreas J. Smout, Albert J. Bredenoord, Ad Masclee, José M. Conchillo Background: Two open-label trials have shown that Electrical stimulation therapy (EST) of the lower esophageal sphincter (LES) (LES-EST) significantly improves esophageal acid exposure and symptoms in GERD patients. However, the underlying antireflux mechanism(s) of LES-EST remain(s) unclear. The aim of this study is to evaluate the effect of EST on postprandial reflux mechanisms, especially on transient LES relaxations (TLESRs). Methods: We studied 10 chronic GERD patients with abnormal acid exposure (pH<4.0 during > 6% of time) and hiatal hernia <3 cm (3 males; mean age 53, range 32-66 yrs). Bipolar stitch electrodes and a pulse generator (EndoStim BV, The Hague, Netherlands) were implanted during laparoscopic surgery. LES-EST was delivered at 20 Hz, 220 µs, 5 mA in 12 30minute sessions. Postprandial reflux mechanisms were studied before and 3 months after EST-implantation, using a combined stationary high-resolution manometry (HRM) and impedance-pH monitoring. Patients consumed a standardized high caloric (500 kCal) meal (cheeseburger, crisps and 200 ml orange juice), followed immediately by a 90-minute measurement. Patients remained in a semi-recumbent position during the measurement and were not allowed to sleep. Results: The majority of postprandial reflux episodes occurred during TLESRs, both before (77%) and after (63%) EST-implantation. After LES-EST, a significant reduction in the total number of TLESRs (from 9.1 (4.0) to 5.6 (3.2), p<0.01) and in the number of TLESRs associated with reflux episodes (from 6.7 (4.1) to 3.8 (3.6), p=0.04) was observed. Total postprandial reflux episodes were not significantly altered by LES-EST (from 9.0 (5.1) to 6.8 (6.1), p=0.14); however, the number of reflux episodes facilitated by TLESRs was significantly reduced (7.0 (3.6) to 3.9 (3.4), p=0.03). The number of reflux episodes induced by other mechanisms (such as abdominal straining or swallowinduced) were unaffected by the treatment. EST showed no effect on the duration of TLESRs (from 17.5 (4.3) s to 14.4 (5.7) s, p=0.14) nor on LES resting pressure (from 19.2 (11.3) mmHg to 21.1 (14.9) mmHg, p=NS). Conclusion: Electrical stimulation therapy of the LES reduced the total number of postprandial TLESRs as well as the number of TLESR-associated reflux episodes in GERD patients. These results suggest that the effect of LES-EST on acid exposure and GERD symptoms is primarily TLESR-mediated.

Su1133 Durability of Effect Following Resolution of Frequent Heartburn With an Over-the-Counter Regimen of Esomeprazole or Placebo for 14 Days David A. Peura, Anne Lemoigne, Heather Wassel, Charles Pollack Objective: Evaluate the impact of achievement of complete resolution of frequent heartburn (HB) on the durability of effect following a 14-day regimen of esomeprazole 20 mg or placebo. Methods: Data were pooled from 2 identical randomized, double-blind, placebocontrolled studies (NCT01370525; NCT01370538) of adults experiencing HB ‡2 days per week in the past 4 weeks treated with esomeprazole 20 mg (administered as esomeprazole magnesium trihydrate 22.3 mg) once daily or placebo for 14 days. Following a 7-day placebo run-in period and 14-day treatment period, all subjects entered a 1-week single-blind placebo follow-up period. Episodes of HB were documented by subjects in daily diaries via an interactive voice response system. The primary efficacy outcome was the percentage of HBfree 24-hour days (defined as days when the subject had no HB episodes). Primary/secondary outcomes have been reported separately elsewhere. The current analysis employed stepwise logistic regression models to identify variables during the run-in and on-treatment periods that were the best predictors of resolution in the follow-up period (defined as 0 or 1 day of HB during the 7-day period). All subjects in the pooled full analysis set who had reported diary data for ‡3 follow-up days were included (N=584). Results: Greater run-in HB frequency was found to be a significant negative predictor of resolution in the follow-up period (P<.001 in both logistic regression models). The best on-treatment predictors of HB resolution during the follow-up period were HB resolution (0 or 1 day of HB) during the last 7 days of treatment and number of days without HB during the full 2 weeks of treatment (Table). Of the subjects who achieved HB resolution during the last 7 days of treatment, 54.5% maintained resolution in the follow-up period, compared with only 19.1% of those who did not achieve resolution during the last 7 days of treatment; the odds of achieving resolution during the follow-up period were 3.8 times greater for subjects achieving resolution in the last 7 days of treatment than for subjects who did not. Subjects who achieved resolution of HB in the follow-up period had a mean of 5.7 days of HB during treatment compared with 10.1 days for subjects not achieving resolution of HB. While holding the number of days with HB during run-in at a fixed value, every 1-day increase in HB-free days during the 2 weeks of treatment increased the odds of HB resolution during the follow-up period by 23.5%. Conclusions: Greater baseline HB frequency decreased the likelihood of resolution in the follow-up. Subjects who achieved HB resolution during the last 7 days of treatment and those with a greater number of days without HB during the 2-week treatment period were more likely to experience durability of effect beyond the treatment period.

Su1131 Preliminary Results of a Prospective Multi-Center Observational Registry of Lower Esophageal Sphincter Stimulation for GERD: The Less-GERD Registry Joachim Labenz, Henning G. Schulz, Andreas Leodolter, Jan B. Pedersen, Ernst Eypasch, Alejandro Nieponice, Ralf Weise, Nicole D. Bouvy Introduction: Electrical stimulation of the lower esophageal sphincter (LES-ES) using the EndoStim® LES Stimulation System (The Hague, The Netherlands) was shown to be effective and safe in clinical trials. Data from routine clinical practice has not yet been reported. Methods: An ongoing, prospective multicenter web-based registry is collecting data at baseline and at routine follow-ups for 5-year in patients with disruptive GERD symptoms treated with LES-ES in routine clinical practice. Demographics, adverse events, GERD symptoms recorded in daily diaries, GERD health related quality of life scores (GERD-HRQL), structured GI symptom questionnaires for extra-esophageal symptoms, use of proton pump inhibitors (PPIs) and objective endoscopic and physiological data (esophageal pH / manometry) are collected when available. Results: Eighty-nine patients are enrolled in the LESSGERD Registry, of whom 39 have available data at baseline and 6 months post-op. All but three (36/39; 92%) patients showed an improvement in their GERD-HRQL score on LESES compared to baseline. Overall, the median (IQR) composite GERD-HRQL score improved from 22 (18-27) preoperatively to 8.0 (3.5-12.5) at 6-month follow-up (p <0.0001). Median distal esophageal acid exposure improved from 11.7 (5.0-24.0)% at baseline to 5.1(2.012.6)% at 6 months (n=17; p=0.59). Proportion of patients with moderate to severe regurgitation decreased from 70% while on medication therapy preoperatively to 27% after 6 months of LES-ES (p<0.04). Proportion of patients with bothersome reflux symptoms during sleep improved from 71% pre-op to 20% at 6 months (p<0.004). Proportion of patients with

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