- Email: [email protected]
Mo1138 The Pharmacokinetics and Pharmacodynamics of Dexlansoprazole Orally-Disintegrating Tablet
AGA Abstracts Mo1136 Mo1137
The Effect of Swallowing on Esophageal Basal Impedance Measurement Using 24 hr Esophageal pH Impedance Monitoring in Patients With Typical Refluxes Symptoms and No Esophagitis Suppakorn Malikhao, Tanisa Patcharatrakul, Sutep Gonlachanvit
Use of a Sleep Positioning Device Significantly Improves Nocturnal Gastroesophageal Reflux Symptoms Sanath Allampati, Rocio Lopez, Prashanthi N. Thota, Monica Ray, Sigurbjorn Birgisson, Scott L. Gabbard
Basal esophageal impedance measurement has been reported as a good diagnostic tool for GERD. To investigate the effect of swallows, meal ingestion and sleep periods on basal esophageal impedance, patients with typical GERD symptoms and no esophagitis who underwent 24 hr esophageal impedance - pH monitoring during off treatment using the VersaFlex® Z pH-impedance catheter and the Omega®, MMS system were included. The basal impedance level was the average values of 30 second-periods at the distal impedance channel, excluding periods of meal ingestion, swallows, belching and gastroesophageal refluxes. Basal impedance levels and swallow frequency were measured every 30 min during the entire recoding periods. Complete and incomplete saliva swallowing were defined as bolus entry followed by bolus clearance at all impedance recording sites and by failure bolus clearance in the two distal recording sites, respectively. Result: 23 consecutive patients with positive pH test(12F, 50 ±14 yr, BMI 26.9±5.0 kg/m2) and 23 patients with negative pH test(14F, 52±13yr, BMI 23.5±3.3 kg/m2, randomly selected from the patients who had typical reflux symptoms and negative pH test during the same study period) were included. The rate of total swallows during the 24 hr study period was similar between patients with positive and negative pH test, respectively (7.5±5.9vs.7.0±5.1 time/hr, p>0.05). The mean basal impedance during the entire study period was significant lower in patients with positive vs. negative pH test (1836±218 vs. 2866±350V , p<0.05). The basal impedance levels had a significantly positive correlation with total (r=0.26, p<0.05) and complete swallowing rate (r=0.3, p<0.05) in the whole 46 patients and both positive (total swallows r=0.38, p<0.05, complete swallows r=0.46, p<0.05) ) and negative pH groups (r = 0.38 and 0.37 respectively, p<0.05). Immediately after meal ingestion the basal impedance level and swallowing rate were significantly higher(3478±947V and 16.9±5.9 time /hr during 0-30 min after meal) compared to before meal (2022±670V and 3.4±2.1 time/hr) (p<0.05) and both basal impedance and swallowing rate gradually decreased over time (during 30-60 min were 2832±705V and 11.8±4.4 time/hr and 60-90 min after meal were 2280±712V and 6.9±3.2 time/hr). The basal impedance and swallowing rate of sleep-time period were significant lower than non sleep- time period (1625±603V vs.2286±660V, p<0.05 and 1.9±1.5 vs.7.5±6.4 time/hr, p<0.05). Conclusion: Swallow, meal ingestion, sleep and acid reflux status are significantly influence basal esophageal impedance level. The lower basal impedance during sleep and higher basal impedance after meal ingestion seems to be the effect of decrease and increase swallowing rate, respectively. This study suggest that control swallowing rate could optimize the measurement of esophageal basal impedance in shorter duration.
Purpose: A recent study demonstrated a decrease in nocturnal acid exposure and reflux episodes in healthy volunteers who slept using a sleep positioning device (SPD) consisting of a two-component incline base (9 inches in height) and a lateral positioner body pillow (Medcline, Amenity Health Inc., San Diego, CA). The purpose of this study is to determine if the use of this SPD decreases nocturnal symptoms in patients with GERD. Methods: This is a single center prospective trial involving patients on anti-secretory medications with continued frequent moderate to severe nocturnal heartburn and regurgitation. Patients completed the Nocturnal GERD Symptom Severity and Impact Questionnaire (N-GSSIQ) and GERD health related quality of life questionnaire (GERD-HRQL) at enrollment. The NGSSIQ and GERD-HRQL are validated questionnaires and N-GSSIQ is comprised of three parts (nocturnal GERD symptoms, morning impact of GERD and concerns about nocturnal GERD). Patients were instructed to sleep on the SPD for at least 6 hours a night during the two week study period, patients were instructed to continue their baseline anti-secretory medication dose. At the end of the two week trial, the questionnaires were repeated. All analyses were performed using SAS (version 9.4, The SAS Institute, Cary, NC). Results: A total of 25 patients (14 female and 11 male; age 58.4±13.4) were recruited from an outpatient Gastroenterology clinic. 24 patients were currently taking proton pump inhibitor (PPI), one patient (intolerant to PPI) was taking H2 receptor antagonist (H2RA). NGSSIQ scores significantly improved over baseline after 2 weeks of SPD use (mean 54.6 [pre] vs. 17.0 [post], p < 0.001). Significant improvement was also noted in all three subsets of the NGSSIQ: nocturnal GERD (33.6 vs. 9.3, p < 0.001), morning impact of nocturnal GERD (6.2 vs. 2.2, p < 0.001) and concern about nocturnal GERD (14.7 vs. 5.5, p < 0.001). 16 patients completed the GERD-HRQL questionnaire, significant improvement was also noted (28.4 vs. 16.3, p < 0.001). No adverse events were reported. Conclusion: In patients with nocturnal heartburn and regurgitation despite anti-secretory medication use, the Medcline SPD significantly reduced nocturnal GERD symptoms, morning impact of nocturnal GERD, concern about nocturnal GERD and helped improve health related quality of life after two weeks of use.
Figure 1: Improvement in GERD symptoms after use of SPD Mo1138 The Pharmacokinetics and Pharmacodynamics of Dexlansoprazole OrallyDisintegrating Tablet Michael Kukulka, Sai Vamshidhar Nudurupati, Maria Claudia Perez Introduction: The proton pump inhibitor dexlansoprazole (DEX) is administered as a modified release (MR) formulation consisting of 2 types of granules within a single capsule. DEX delayed-release capsules are approved for use in adults for treatment of heartburn associated with symptomatic nonerosive gastroesophageal reflux disease (GERD), healing of erosive esophagitis (EE), and maintenance of healed EE and relief of heartburn. Since some patients are unable or unwilling to swallow capsules, a DEX delayed-release orallydisintegrating tablet (OD) has been developed. DEX OD contains 2 types of granules that release drug in a pH-dependent manner in order to extend DEX plasma concentrations. Objective: To assess the pharmacokinetics (PK) and pharmacodynamics (PD) of DEX OD 30 mg and DEX MR 30 mg capsule. Methods: This was a randomized, multiple-dose, 2period crossover study. Healthy subjects 21-55 years old received 30 mg DEX OD or capsule
S-617
AGA Abstracts
AGA Abstracts
once daily for 5 days. There was a 7-day washout between the last dose in Period 1 and the first dose in Period 2. Blood samples for plasma PK were collected for 24 hours post-dose on Days 1 and 5 of each period. Analyses of variance (ANOVA) models were performed, and bioequivalence (BE) between the OD and the capsule was declared if 90% confidence intervals (CIs) of central value ratios between 2 regimens for the Day 1 and 5 maximum plasma concentration (Cmax) and area under the curve (AUC) were within the BE limits of 0.80-1.25. PD was assessed via 24-hour intragastric pH monitoring starting immediately prior to dose on Days 1 and 5 of each period. ANOVA models were fitted to the Day 1 and 5 PD parameters and 90% CIs for the difference in the least squares means of the 2 regimens were computed. PD equivalence was concluded if the 90% CIs were contained within the range of (-12%, 12%) for % time pH>4 over the 24-hour interval. Safety was assessed via physical examination (PE), clinical laboratory evaluation, vital sign assessment, electrocardiograms (ECG), and adverse event reports (AE). Results: 52 subjects (mean age 40±10.2 years) were enrolled. The 90% CIs for the relative bioavailability of DEX from DEX OD 30 mg to capsule for Cmax and AUCs were within the BE range of 0.80-1.25 for both Days 1 and 5. For Days 1 and 5, the 90% CIs for the differences in LS means of % time pH>4 between OD and capsule were within the (-12%, 12%) equivalence range. Both regimens were well tolerated. AEs were primarily mild in intensity and were considered unrelated to study drug. Percentages of subjects experiencing AEs were comparable for both regimens. There were no clinically important findings noted in the PE, safety clinical laboratory, vital sign, or ECG reports. Conclusions: DEX OD 30 mg and DEX MR 30 mg capsules provide equivalent plasma exposure and intragastric pH control. DEX OD and DEX MR capsules were well tolerated. Table 1. Bioequivalence Assessment of DEX OD
Mo1140 Clinical Efficacy of Diaphragmatic Breathing in Patients With Symptomatic Belching Andrew Ming Liang Ong, Laura Chua, Yu Tien Wang BACKGROUND & AIMS: Belching is a common symptom in patients referred to gastroenterology clinics, especially in patients with Gastro-Esophageal Reflux Disease (GERD). Studies suggest that in patients with GERD, these belches can induce reflux episodes. Treatment options are disappointing and limited for these patients. It has been suggested that in many patients with excessive belching, a supragastric pattern characterized by a rapid influx of air, followed by a rapid air expulsion is seen. This is an involuntary behavioural disorder that may respond to Diaphragmatic Breathing (DB) exercises according to a pilot study in 2010 by Hemmink et al. Since then, there has been no further study looking at the clinical efficacy of DB in belching patients. In the pilot, 6/17 patients defaulted further follow up and hence the actual clinical efficacy of DB may be even higher than reported. Our study aimed to look at the efficacy of DB in patients with symptomatic belching and also to evaluate if compliance to home exercises affect clinical outcomes. METHODS: Retrospective study of the effect of DB exercises on all belching patients who were referred to our center's speech therapy department for DB exercises between July 2012 and June 2014 was conducted. Primary outcome was patient reported improvement of symptoms. All patients underwent a standardized DB training protocol by trained speech therapists. Statistical analysis via Chi2 test for categorical variables was done. RESULTS: 35 patients (60% female, mean age 58 +/- 14) were referred for DB therapy. 10 patients were uncontactable and excluded from analysis. Of these 25 analyzed patients, 20 had belching as a predominant symptom (3 with belching only, 6 with concomitant dyspepsia, 11 with concomitant GERD symptoms). The predominant symptoms in the other 5 patients were 3 regurgitations, 1 globus and 1 vomiting. 55% (11/20) of patients with belching reported improvement of symptoms after a median of 3 sessions of DB therapy. There was no difference in outcomes between patients with belching only or with concomitant symptoms of GERD (50%, 6/12, p=0.85) and dyspepsia (43%, 3/7, p=0.67). 77% (10/13) of patients who had improvement in symptoms were compliant to home exercises of DB compared to those without improvement (17%, 2/12, p=0.05). 38% (5/13) of patients who were non-compliant did so because they were unable to follow instructions. CONCLUSIONS: Our results suggest that DB was a useful for patients with symptomatic belching as majority showed improvement after a median of 3 sessions, and that this was also seen in patients with concomitant GERD or dyspepsia. Patients were significantly more likely to report improvement if they were compliant to DB home exercises. Our data suggest that the inability to follow instructions was the main reason for non-compliance, and this may be an area for improvement.
AUCt = AUC from time zero to the last quantifiable concentration; AUC∞= AUC from time zero to infinity. Note: N=(Test/Reference). Note: The subjects with valid estimates for reference and at least 1 other administration routes were included in the analysis for that parameter. Table 2. pH Assessment of DEX OD and DEX MR Capsule
(a) P-values and 90% CIs are from an ANOVA with effects for regimen, sequence, period and subject nested within sequence. Note: Subjects with a PD parameter estimated for both regimens were included in the analyses.
Mo1141 The Feasibility and Acceptability of Esophageal-Directed Hypnotherapy for Functional Heartburn Megan E. Riehl, John E. Pandolfino, Olafur S. Palsson, Laurie Keefer
Mo1139 Modulation of Pulse Parameters for Electrical Stimulation of the Lower Esophageal Sphincter Marc Cole, Takahide Kato, Stanley Yamashiro, Edy Soffer
Background: Functional Heartburn (FH) is a benign but burdensome condition characterized by painful, burning epigastric sensations in the absence of acid reflux or symptom-reflux correlation. Esophageal hypersensitivity and its psychological counterpart, esophageal hypervigilance (EHv) drive symptom experience. Hypnotherapy (HYP) is an established and preferred intervention for refractory symptoms in functional gastrointestinal disorders (FGIDs) but has not been formally tested for FH. Methods: We recruited 9 consecutive patients who had undergone 96h ph impedence testing and who met Rome III criteria for FH to participate in 7 sessions of weekly esophageal directed hypnotherapy (EHYP). EHYP was adapted from the validated North Carolina IBS protocol and included suggestions specific to heartburn, chest pain, hypersensitivity and acid. Each participant completed questionnaires to assess demographics and clinical characteristics, esophageal symptoms (QOLRAD), health-related physical and emotional quality of life (SF12v2), visceral sensitivity (VSI) and perceived stress (Heartburn Catastrophizing Scale) at baseline and 1 week followup. Hypnotizability was assessed with the Tellegen Absorption Scale. A Global Impression of Change rating was obtained at post-treatment. Results: Nine (8 women, 1 man) FH patients aged 32-60 years (mean=44.9) enrolled in this pilot study. All were married with at least a high school education. Seven of 9 completed treatment and 2 patients were included as intent to treat after completing 2-3 sessions. There were no differences between treatment completers vs. non-completers on demographics or baseline characteristics. At baseline, heartburn symptom severity varied widely [Median QOLRAD = 3.68, range 2.12 to 5.52]. Paired sample t-tests showed decrease in visceral anxiety, an increase in emotional QOL, a decrease in symptom severity and a trend for reduction in heartburn catastrophizing after hypnosis treatment (Table 1). There was no significant change in physical QOL. Hypnotizability was not correlated with outcome measures. All participants reported improvement in symptoms post-treatment; 50% reported their esophageal symptoms as "Substantially Improved", while 50% reported their symptoms as "Slightly Improved" at the conclusion of treatment. Conclusions: Esophageal directed hypnotherapy was feasible and acceptable to patients with FH regardless of hypnotizability. Similar to other work in FGIDs there were
Background: Existing implantable devices for electrical stimulation of the gut smooth muscle, and in particular the lower esophageal sphincter (LES) to treat gastroesophageal reflux disease (GERD), use pulse width of <1 msec, that target neural elements. Aim: To explore the contractile effect, and required energy, of a range of pulse parameters on pig LES muscle in vitro. Methods: Muscle strips from 7 pig LES muscle were exposed to electrical field stimulation (EFS) under physiological conditions. Contractile response to a 1 second stimulation with trains of pulses of up to 80 mAmp (3.2 volts/cm field stimulation), frequency of up to 50 Hz and duration of up to 50msec was compared to a 1 second single energymatched control pulses. Results: Pulses with a duty cycle of 20-40% and 40 mAmp generated more than twice the force of the control pulse (Figure). Stimulation at 20 ma (.8 volts/cm field stimulation),5 msec pulse duration, and 20 Hz resulted in a higher force than control. power consumption was 1.6 times higher than for the reported stimulation used in humans for GERD treatment with nominal parameters (5 ma,.215 msec,20 Hz)and, but was equal when current was increased above nominal, to 6 ma. Tetrodotoxin did not significantly change the responses to pulses > 1 msec duration. Conclusion: Contractile force generated by direct smooth muscle stimulation was consistently higher than for neural stimulation as measured by responses to 1 msec pulses. Such stimulation may be considered for treatment of weak sphincteric muscles.
AGA Abstracts
S-618
The Effect of Swallowing on Esophageal Basal Impedance Measurement Using 24 hr Esophageal pH Impedance Monitoring in Patients With Typical Refluxes Symptoms and No Esophagitis Suppakorn Malikhao, Tanisa Patcharatrakul, Sutep Gonlachanvit
Use of a Sleep Positioning Device Significantly Improves Nocturnal Gastroesophageal Reflux Symptoms Sanath Allampati, Rocio Lopez, Prashanthi N. Thota, Monica Ray, Sigurbjorn Birgisson, Scott L. Gabbard
Basal esophageal impedance measurement has been reported as a good diagnostic tool for GERD. To investigate the effect of swallows, meal ingestion and sleep periods on basal esophageal impedance, patients with typical GERD symptoms and no esophagitis who underwent 24 hr esophageal impedance - pH monitoring during off treatment using the VersaFlex® Z pH-impedance catheter and the Omega®, MMS system were included. The basal impedance level was the average values of 30 second-periods at the distal impedance channel, excluding periods of meal ingestion, swallows, belching and gastroesophageal refluxes. Basal impedance levels and swallow frequency were measured every 30 min during the entire recoding periods. Complete and incomplete saliva swallowing were defined as bolus entry followed by bolus clearance at all impedance recording sites and by failure bolus clearance in the two distal recording sites, respectively. Result: 23 consecutive patients with positive pH test(12F, 50 ±14 yr, BMI 26.9±5.0 kg/m2) and 23 patients with negative pH test(14F, 52±13yr, BMI 23.5±3.3 kg/m2, randomly selected from the patients who had typical reflux symptoms and negative pH test during the same study period) were included. The rate of total swallows during the 24 hr study period was similar between patients with positive and negative pH test, respectively (7.5±5.9vs.7.0±5.1 time/hr, p>0.05). The mean basal impedance during the entire study period was significant lower in patients with positive vs. negative pH test (1836±218 vs. 2866±350V , p<0.05). The basal impedance levels had a significantly positive correlation with total (r=0.26, p<0.05) and complete swallowing rate (r=0.3, p<0.05) in the whole 46 patients and both positive (total swallows r=0.38, p<0.05, complete swallows r=0.46, p<0.05) ) and negative pH groups (r = 0.38 and 0.37 respectively, p<0.05). Immediately after meal ingestion the basal impedance level and swallowing rate were significantly higher(3478±947V and 16.9±5.9 time /hr during 0-30 min after meal) compared to before meal (2022±670V and 3.4±2.1 time/hr) (p<0.05) and both basal impedance and swallowing rate gradually decreased over time (during 30-60 min were 2832±705V and 11.8±4.4 time/hr and 60-90 min after meal were 2280±712V and 6.9±3.2 time/hr). The basal impedance and swallowing rate of sleep-time period were significant lower than non sleep- time period (1625±603V vs.2286±660V, p<0.05 and 1.9±1.5 vs.7.5±6.4 time/hr, p<0.05). Conclusion: Swallow, meal ingestion, sleep and acid reflux status are significantly influence basal esophageal impedance level. The lower basal impedance during sleep and higher basal impedance after meal ingestion seems to be the effect of decrease and increase swallowing rate, respectively. This study suggest that control swallowing rate could optimize the measurement of esophageal basal impedance in shorter duration.
Purpose: A recent study demonstrated a decrease in nocturnal acid exposure and reflux episodes in healthy volunteers who slept using a sleep positioning device (SPD) consisting of a two-component incline base (9 inches in height) and a lateral positioner body pillow (Medcline, Amenity Health Inc., San Diego, CA). The purpose of this study is to determine if the use of this SPD decreases nocturnal symptoms in patients with GERD. Methods: This is a single center prospective trial involving patients on anti-secretory medications with continued frequent moderate to severe nocturnal heartburn and regurgitation. Patients completed the Nocturnal GERD Symptom Severity and Impact Questionnaire (N-GSSIQ) and GERD health related quality of life questionnaire (GERD-HRQL) at enrollment. The NGSSIQ and GERD-HRQL are validated questionnaires and N-GSSIQ is comprised of three parts (nocturnal GERD symptoms, morning impact of GERD and concerns about nocturnal GERD). Patients were instructed to sleep on the SPD for at least 6 hours a night during the two week study period, patients were instructed to continue their baseline anti-secretory medication dose. At the end of the two week trial, the questionnaires were repeated. All analyses were performed using SAS (version 9.4, The SAS Institute, Cary, NC). Results: A total of 25 patients (14 female and 11 male; age 58.4±13.4) were recruited from an outpatient Gastroenterology clinic. 24 patients were currently taking proton pump inhibitor (PPI), one patient (intolerant to PPI) was taking H2 receptor antagonist (H2RA). NGSSIQ scores significantly improved over baseline after 2 weeks of SPD use (mean 54.6 [pre] vs. 17.0 [post], p < 0.001). Significant improvement was also noted in all three subsets of the NGSSIQ: nocturnal GERD (33.6 vs. 9.3, p < 0.001), morning impact of nocturnal GERD (6.2 vs. 2.2, p < 0.001) and concern about nocturnal GERD (14.7 vs. 5.5, p < 0.001). 16 patients completed the GERD-HRQL questionnaire, significant improvement was also noted (28.4 vs. 16.3, p < 0.001). No adverse events were reported. Conclusion: In patients with nocturnal heartburn and regurgitation despite anti-secretory medication use, the Medcline SPD significantly reduced nocturnal GERD symptoms, morning impact of nocturnal GERD, concern about nocturnal GERD and helped improve health related quality of life after two weeks of use.
Figure 1: Improvement in GERD symptoms after use of SPD Mo1138 The Pharmacokinetics and Pharmacodynamics of Dexlansoprazole OrallyDisintegrating Tablet Michael Kukulka, Sai Vamshidhar Nudurupati, Maria Claudia Perez Introduction: The proton pump inhibitor dexlansoprazole (DEX) is administered as a modified release (MR) formulation consisting of 2 types of granules within a single capsule. DEX delayed-release capsules are approved for use in adults for treatment of heartburn associated with symptomatic nonerosive gastroesophageal reflux disease (GERD), healing of erosive esophagitis (EE), and maintenance of healed EE and relief of heartburn. Since some patients are unable or unwilling to swallow capsules, a DEX delayed-release orallydisintegrating tablet (OD) has been developed. DEX OD contains 2 types of granules that release drug in a pH-dependent manner in order to extend DEX plasma concentrations. Objective: To assess the pharmacokinetics (PK) and pharmacodynamics (PD) of DEX OD 30 mg and DEX MR 30 mg capsule. Methods: This was a randomized, multiple-dose, 2period crossover study. Healthy subjects 21-55 years old received 30 mg DEX OD or capsule
S-617
AGA Abstracts
AGA Abstracts
once daily for 5 days. There was a 7-day washout between the last dose in Period 1 and the first dose in Period 2. Blood samples for plasma PK were collected for 24 hours post-dose on Days 1 and 5 of each period. Analyses of variance (ANOVA) models were performed, and bioequivalence (BE) between the OD and the capsule was declared if 90% confidence intervals (CIs) of central value ratios between 2 regimens for the Day 1 and 5 maximum plasma concentration (Cmax) and area under the curve (AUC) were within the BE limits of 0.80-1.25. PD was assessed via 24-hour intragastric pH monitoring starting immediately prior to dose on Days 1 and 5 of each period. ANOVA models were fitted to the Day 1 and 5 PD parameters and 90% CIs for the difference in the least squares means of the 2 regimens were computed. PD equivalence was concluded if the 90% CIs were contained within the range of (-12%, 12%) for % time pH>4 over the 24-hour interval. Safety was assessed via physical examination (PE), clinical laboratory evaluation, vital sign assessment, electrocardiograms (ECG), and adverse event reports (AE). Results: 52 subjects (mean age 40±10.2 years) were enrolled. The 90% CIs for the relative bioavailability of DEX from DEX OD 30 mg to capsule for Cmax and AUCs were within the BE range of 0.80-1.25 for both Days 1 and 5. For Days 1 and 5, the 90% CIs for the differences in LS means of % time pH>4 between OD and capsule were within the (-12%, 12%) equivalence range. Both regimens were well tolerated. AEs were primarily mild in intensity and were considered unrelated to study drug. Percentages of subjects experiencing AEs were comparable for both regimens. There were no clinically important findings noted in the PE, safety clinical laboratory, vital sign, or ECG reports. Conclusions: DEX OD 30 mg and DEX MR 30 mg capsules provide equivalent plasma exposure and intragastric pH control. DEX OD and DEX MR capsules were well tolerated. Table 1. Bioequivalence Assessment of DEX OD
Mo1140 Clinical Efficacy of Diaphragmatic Breathing in Patients With Symptomatic Belching Andrew Ming Liang Ong, Laura Chua, Yu Tien Wang BACKGROUND & AIMS: Belching is a common symptom in patients referred to gastroenterology clinics, especially in patients with Gastro-Esophageal Reflux Disease (GERD). Studies suggest that in patients with GERD, these belches can induce reflux episodes. Treatment options are disappointing and limited for these patients. It has been suggested that in many patients with excessive belching, a supragastric pattern characterized by a rapid influx of air, followed by a rapid air expulsion is seen. This is an involuntary behavioural disorder that may respond to Diaphragmatic Breathing (DB) exercises according to a pilot study in 2010 by Hemmink et al. Since then, there has been no further study looking at the clinical efficacy of DB in belching patients. In the pilot, 6/17 patients defaulted further follow up and hence the actual clinical efficacy of DB may be even higher than reported. Our study aimed to look at the efficacy of DB in patients with symptomatic belching and also to evaluate if compliance to home exercises affect clinical outcomes. METHODS: Retrospective study of the effect of DB exercises on all belching patients who were referred to our center's speech therapy department for DB exercises between July 2012 and June 2014 was conducted. Primary outcome was patient reported improvement of symptoms. All patients underwent a standardized DB training protocol by trained speech therapists. Statistical analysis via Chi2 test for categorical variables was done. RESULTS: 35 patients (60% female, mean age 58 +/- 14) were referred for DB therapy. 10 patients were uncontactable and excluded from analysis. Of these 25 analyzed patients, 20 had belching as a predominant symptom (3 with belching only, 6 with concomitant dyspepsia, 11 with concomitant GERD symptoms). The predominant symptoms in the other 5 patients were 3 regurgitations, 1 globus and 1 vomiting. 55% (11/20) of patients with belching reported improvement of symptoms after a median of 3 sessions of DB therapy. There was no difference in outcomes between patients with belching only or with concomitant symptoms of GERD (50%, 6/12, p=0.85) and dyspepsia (43%, 3/7, p=0.67). 77% (10/13) of patients who had improvement in symptoms were compliant to home exercises of DB compared to those without improvement (17%, 2/12, p=0.05). 38% (5/13) of patients who were non-compliant did so because they were unable to follow instructions. CONCLUSIONS: Our results suggest that DB was a useful for patients with symptomatic belching as majority showed improvement after a median of 3 sessions, and that this was also seen in patients with concomitant GERD or dyspepsia. Patients were significantly more likely to report improvement if they were compliant to DB home exercises. Our data suggest that the inability to follow instructions was the main reason for non-compliance, and this may be an area for improvement.
AUCt = AUC from time zero to the last quantifiable concentration; AUC∞= AUC from time zero to infinity. Note: N=(Test/Reference). Note: The subjects with valid estimates for reference and at least 1 other administration routes were included in the analysis for that parameter. Table 2. pH Assessment of DEX OD and DEX MR Capsule
(a) P-values and 90% CIs are from an ANOVA with effects for regimen, sequence, period and subject nested within sequence. Note: Subjects with a PD parameter estimated for both regimens were included in the analyses.
Mo1141 The Feasibility and Acceptability of Esophageal-Directed Hypnotherapy for Functional Heartburn Megan E. Riehl, John E. Pandolfino, Olafur S. Palsson, Laurie Keefer
Mo1139 Modulation of Pulse Parameters for Electrical Stimulation of the Lower Esophageal Sphincter Marc Cole, Takahide Kato, Stanley Yamashiro, Edy Soffer
Background: Functional Heartburn (FH) is a benign but burdensome condition characterized by painful, burning epigastric sensations in the absence of acid reflux or symptom-reflux correlation. Esophageal hypersensitivity and its psychological counterpart, esophageal hypervigilance (EHv) drive symptom experience. Hypnotherapy (HYP) is an established and preferred intervention for refractory symptoms in functional gastrointestinal disorders (FGIDs) but has not been formally tested for FH. Methods: We recruited 9 consecutive patients who had undergone 96h ph impedence testing and who met Rome III criteria for FH to participate in 7 sessions of weekly esophageal directed hypnotherapy (EHYP). EHYP was adapted from the validated North Carolina IBS protocol and included suggestions specific to heartburn, chest pain, hypersensitivity and acid. Each participant completed questionnaires to assess demographics and clinical characteristics, esophageal symptoms (QOLRAD), health-related physical and emotional quality of life (SF12v2), visceral sensitivity (VSI) and perceived stress (Heartburn Catastrophizing Scale) at baseline and 1 week followup. Hypnotizability was assessed with the Tellegen Absorption Scale. A Global Impression of Change rating was obtained at post-treatment. Results: Nine (8 women, 1 man) FH patients aged 32-60 years (mean=44.9) enrolled in this pilot study. All were married with at least a high school education. Seven of 9 completed treatment and 2 patients were included as intent to treat after completing 2-3 sessions. There were no differences between treatment completers vs. non-completers on demographics or baseline characteristics. At baseline, heartburn symptom severity varied widely [Median QOLRAD = 3.68, range 2.12 to 5.52]. Paired sample t-tests showed decrease in visceral anxiety, an increase in emotional QOL, a decrease in symptom severity and a trend for reduction in heartburn catastrophizing after hypnosis treatment (Table 1). There was no significant change in physical QOL. Hypnotizability was not correlated with outcome measures. All participants reported improvement in symptoms post-treatment; 50% reported their esophageal symptoms as "Substantially Improved", while 50% reported their symptoms as "Slightly Improved" at the conclusion of treatment. Conclusions: Esophageal directed hypnotherapy was feasible and acceptable to patients with FH regardless of hypnotizability. Similar to other work in FGIDs there were
Background: Existing implantable devices for electrical stimulation of the gut smooth muscle, and in particular the lower esophageal sphincter (LES) to treat gastroesophageal reflux disease (GERD), use pulse width of <1 msec, that target neural elements. Aim: To explore the contractile effect, and required energy, of a range of pulse parameters on pig LES muscle in vitro. Methods: Muscle strips from 7 pig LES muscle were exposed to electrical field stimulation (EFS) under physiological conditions. Contractile response to a 1 second stimulation with trains of pulses of up to 80 mAmp (3.2 volts/cm field stimulation), frequency of up to 50 Hz and duration of up to 50msec was compared to a 1 second single energymatched control pulses. Results: Pulses with a duty cycle of 20-40% and 40 mAmp generated more than twice the force of the control pulse (Figure). Stimulation at 20 ma (.8 volts/cm field stimulation),5 msec pulse duration, and 20 Hz resulted in a higher force than control. power consumption was 1.6 times higher than for the reported stimulation used in humans for GERD treatment with nominal parameters (5 ma,.215 msec,20 Hz)and, but was equal when current was increased above nominal, to 6 ma. Tetrodotoxin did not significantly change the responses to pulses > 1 msec duration. Conclusion: Contractile force generated by direct smooth muscle stimulation was consistently higher than for neural stimulation as measured by responses to 1 msec pulses. Such stimulation may be considered for treatment of weak sphincteric muscles.
AGA Abstracts
S-618