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Su1589 Blunted Contractility in Slow Transit Constipation During Awakening Compared to Healthy and Normal Transit Constipation Subjects as Evaluated by Wireless Motility Capsule
important risk factor. The overlap of these two entities may be related to same pathophysiological mechanisms, but also it is possible that one condition may predispose to the other one. For example, excessive pushing in patients with constipation-GERD or older age in patients with GERD-constipation.
Su1589 Blunted Contractility in Slow Transit Constipation During Awakening Compared to Healthy and Normal Transit Constipation Subjects as Evaluated by Wireless Motility Capsule Brian Surjanhata, Laurence Guay, Braden Kuo
Su1587 Neostigmine and Glycopyrrolate Delivered Transdermally by Iontophoresis Safely Stimulates Bowel Evacuation in Persons With Spinal Cord Injury: A Novel Approach to Bowel Care Mark A. Korsten, Miroslav Radulovic, Brian Lyons, Ravi Vinnakota, Kamaldeep Singh, Joshua Hobson, Sandeep Kahal, Oriana Tascione, Ann M. Spungen, Marinella D. Galea, William A. Bauman
Background Diurnal variation on colonic motility in healthy individuals is a well-described phenomenon described as decreased contractile activity during sleep, with significant contractility during waking hours. This has been evaluated to some limited extent before with 24hour colonic manometry studies using catheters with solid-state probes. The invasive nonambulatory nature, bowel preparation, and sedation potentially alters physiological conditions while trying to study a physiological phenomenon. Wireless Motility Capsule (WMC) is a non-invasive measure of transit and contractility approved for evaluation of constipation that provides a unique non-invasive opportunity to study colonic contractility under more physiological conditions. Aims 1) Determine if WMC is able to detect sleep/wake colonic contractile variation. 2) Elucidate differences between healthy and symptomatic constipation subjects with normal transit (NTC) and slow transit constipation (STC). Methods We reviewed WMC data obtained from three previous clinical trials. Number of contractions (Ct), area under the curve (AUC), and motility index (MI) from healthy and constipated subjects were analyzed 1 hour pre-wake (baseline) and post-wake event as defined by diary entry in 20 minute windows. The first two pre-wake 20-minute windows were used as baseline. The 20 minutes immediately prior to wake was omitted from baseline analysis to avoid errors from imprecise diary entry of when people actually awoke. NTC/STC was determined by WMC colonic transit time (CTT). T-tests with bonferroni correction compared contractility parameters between subjects and between baseline and post-wake. Results A total of 24 healthy and 21 constipated subjects were analyzed, of which 9 were NTC and 12 were STC. Healthy subjects had 29 wake events and constipated subjects had 43 wake events (12 in NTC and 31 in STC). Average CTT was 1654 minutes for healthy, 2492 minutes for NTC and 5781 minutes for STC. After wakening, healthy, NTC, and STC subjects showed increased absolute contractility parameters (Ct, AUC, and MI) compared to baseline in all post-wake windows (p < 0.01). Contractile parameters (Ct, AUC, and MI) were significantly decreased in STC versus healthy subjects in the immediate 20 minutes after wake (p < 0.001). (Fig 1) Conclusion WMC is able to capture diurnal variation in colonic contractile activity. NTC and STC subjects have an intact increase in contractility parameters (Ct, AUC, and MI) upon wake as in healthy subjects. However, in the STC subset these contractility parameters are significantly decreased in the immediate 20 minutes after wake compared to healthy controls indicating a blunted response. This may suggest some unique neuropathic process contributing to STC.
BACKGROUND: Difficulty with evacuation is a common clinical problem after spinal cord injury (SCI) and other disorders characterized by constipation. Our group reported that intravenous (IV) administration of neostigmine and glycopyrrolate (NEO/GLY) safely and rapidly promotes bowel evacuation (AJG, 100:1560,2005). Because IV administration of these agents is of limited practical value for routine bowel care, a non-parenteral approach to drug delivery was investigated. Iontophoretic (ION) technology that employs an electric field to non-invasively drive polar ions across the skin was tested as a viable drug delivery approach to achieve safe, predictable bowel evacuation. AIMS: To determine whether transdermal (TD) administration of NEO/GLY by ION technology: 1) promotes increased bowel motility and evacuation and 2) has an acceptable safety profile. METHODS: The ION system consisted of Dynatron iBoxes™ delivered a positive current of 4.0 mA-min x 10 min via a dermal patch. Those with a history of cardiovascular or pulmonary complications were excluded from the study. At Visit 1, subjects were screened for responsiveness to IV NEO (0.03 mg/kg)/GLY (0.006 mg/kg). Those with a positive response to IV NEO/GLY progressed to Visit 2 to receive low-dose TD NEO (0.05 mg/kg)/GLY (0.01 mg/kg). Those who failed to have drug-related symptoms and/or a bowel movement after administration of low-dose TD NEO/GLY were administered high-dose TD NEO (0.07 mg/kg)/GLY (0.014 mg/kg) at Visit 3. After TD drug administration, defecation, increased bowel sounds, and other cholinergic side effects were assessed every 5 min for 1 hour. RESULTS: 23 subjects were screened with IV NEO/GLY; 17 of 23 subjects had a bowel movement (21±23 min); 22 of 23 subjects reported drug-related side effects (i.e., presence of eye twitching, cramping, and/ or defecation). 20 subjects who reported a positive drug-related response after IV NEO/GLY progressed to Visit 2; after low-dose TD NEO/GLY, 5 of 20 subjects (25%) had bowel evacuation (36±15 min), and 12 subjects (60%) had drug-related responses. 14 subjects who did not have cholinergic responses at Visit 2 then progressed to receive a higher dose of TD NEO/GLY at Visit 3; 5 of 14 subjects (35.7%) had bowel evacuation (26±22min) and 12 (85.7%) had drug-related responses. Overall, 50% of subjects had bowel evacuations with either low-or high-dose TD NEO/GLY. Cardiopulmonary measurements were not clinically altered during any of the study visits. No statistical differences were observed in bowel evacuation time between IV screening vs. either low-dose (p=0.10) or high-dose (p= 0.68) TD NEO/GLY. CONCLUSIONS: TD NEO/GLY may be safely administered by ION to induce increased bowel motility and evacuation. Thus, TD NEO/GLY may improve bowel care in persons with SCI and, perhaps, other conditions characterized by prolonged colonic transit time.
Su1588 Prevalence and Risk Factors of Overlaps Between GERD-Constipation and Constipation-GERD Gabriela Rojas-Loureiro, Ilce Belinda Lazaro Pacheco, Ricardo Flores Rendon, Maria Eugenia Icaza-Chávez, Octavio Gomez-Escudero, Enrique Coss-Adame, Mercedes AmievaBalmori, Olivia Rascon Sosa, Jose M. Remes Troche Introduction: Overlap between different functional gastrointestinal disorders is very common. Several studies have shown that irritable bowel syndrome (IBS), functional dyspepsia (FD) and gastroesophageal reflux disease (GERD) frequently overlaps. Constipation symptoms may affect up to 14 to 22% of the general population, while about 12-15% may suffer of GERD symptoms least 1 time per week (Remes-Troche DDW 2014), so it is logical to think that these entities may alsooverlaps. However, searching in the literature we did not found evidence regarding the overlap between GERD-Constipation or Constipation-GERD symptoms. Aim: To evaluate prevalence and risk factors associated to the overlap between GERD and Constipation and vice versa Materials and Methods: A prolective, cross-sectional study was conducted including consecutive subjects who attended to five third referral centers because the presence of symptoms of GERD and / or constipation. Diagnosis of GERD was done according to the presence of typical symptoms (heartburn and regurgitation) but also using the Carlsson-Dent questionnaire (> 4 points was considered as positive). Constipation symptoms were evaluated using the Rome III criteria for IBS-C, functional constipation (FC) and dyssynergic defecation (DD). Demographic characteristics and factors associated with both conditions were analyzed Results: 324 patients were included, 250 were women (77%) with amean age of 46 ± 16 years. Of these, 206 (64%) attended for GERD and 118 (36%) for constipation symptoms. Among GERD patients, 152 (72%) were women (mean 44.8 ± 14 years) and the overlap with constipationwas 40% (n = 83). Forty had IBS-C, 40 FC and 3 DD. Patients with GERD-Constipation were older (48 ± 14 vs 42 ± 15, p = 0.002). Risk factors for this overlap were female gender (OR = 1.48) and obesity (OR = 2.091). Interestingly, GERD-Constipationpatients reported greater improvement using PPIS compared to patients with only GERD (p = 0.23, OR = 0.379). Among patients who attended for constipation (n=118) (98 women, mean age 48.5 ± 17 years) 71 (62.3%) had IBS-C, 33 (28.9%) had FC, 10 (8.8%) DD and 4 were unclassified. In constipation patients overlapping with GERD was 56% (n = 64). Risks factors for Constipation-GERD were obesity (OR 1.38) and the presence of excessive pushing (RM 2.86). Conclusions: ConstipationGERD overlap more often than GERD-Constipation. However in both groups obesity is an
Figure 1. Contractility response to wake in healthy, normal transit constipation, and slow transit constipation as compared to baseline windows (* p < 0.01). STC compared to healthy subjects showed significantly decreased Ct immediately after waking (p < 0.001).
Su1590 Factors Associated With the Use of Laxatives in the United States Adult Population Shuji Mitsuhashi, Zhenghui G. Jiang, Judy W. Nee, Mohammed Zakari, Anthony Lembo Background: Constipation is one of the most common gastrointestinal complaints in an ambulatory setting. Laxatives, treatments for constipation, are readily accessible. However, the prevalence and determinants of laxative use in the community is not well understood. We sought to describe the prevalence and factors associated with laxative use in a cohort representative of the US adult population. Method: Using data from the 2009-2010 National Health and Nutrition Examination Surveys (NHANES), the use of laxatives was identified from the questionnaire on bowel health provided by 6,059 study subjects enrolled. We investigated potential factors that are associated with laxative use, including demographics, medical history, bowel health, and socio-economic status. Their relationships with laxative use were studied by both univariate and multivariate regression models adjusting for sampling weights that reconstituted the US population. Results: Among the US adult population age
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CI=confidence interval; CIC=chronic idiopathic constipation. *N=302, 122, 118 and 62 for patients receiving placebo in the pooled population and Studies 1, 2 and 3, respectively. † N=301, 120, 119 and 62 for patients treated with lubiprostone in the pooled population and Studies 1, 2 and 3, respectively. ‡Stool consistency responders: 1-unit improvement from baseline on a 5- or 7-point scale each week for ‡3 of 4 treatment weeks. **Straining responders: 1-unit improvement from baseline on a 5-point scale each week for ‡3 of 4 treatment weeks.
Su1589 Blunted Contractility in Slow Transit Constipation During Awakening Compared to Healthy and Normal Transit Constipation Subjects as Evaluated by Wireless Motility Capsule Brian Surjanhata, Laurence Guay, Braden Kuo
Su1587 Neostigmine and Glycopyrrolate Delivered Transdermally by Iontophoresis Safely Stimulates Bowel Evacuation in Persons With Spinal Cord Injury: A Novel Approach to Bowel Care Mark A. Korsten, Miroslav Radulovic, Brian Lyons, Ravi Vinnakota, Kamaldeep Singh, Joshua Hobson, Sandeep Kahal, Oriana Tascione, Ann M. Spungen, Marinella D. Galea, William A. Bauman
Background Diurnal variation on colonic motility in healthy individuals is a well-described phenomenon described as decreased contractile activity during sleep, with significant contractility during waking hours. This has been evaluated to some limited extent before with 24hour colonic manometry studies using catheters with solid-state probes. The invasive nonambulatory nature, bowel preparation, and sedation potentially alters physiological conditions while trying to study a physiological phenomenon. Wireless Motility Capsule (WMC) is a non-invasive measure of transit and contractility approved for evaluation of constipation that provides a unique non-invasive opportunity to study colonic contractility under more physiological conditions. Aims 1) Determine if WMC is able to detect sleep/wake colonic contractile variation. 2) Elucidate differences between healthy and symptomatic constipation subjects with normal transit (NTC) and slow transit constipation (STC). Methods We reviewed WMC data obtained from three previous clinical trials. Number of contractions (Ct), area under the curve (AUC), and motility index (MI) from healthy and constipated subjects were analyzed 1 hour pre-wake (baseline) and post-wake event as defined by diary entry in 20 minute windows. The first two pre-wake 20-minute windows were used as baseline. The 20 minutes immediately prior to wake was omitted from baseline analysis to avoid errors from imprecise diary entry of when people actually awoke. NTC/STC was determined by WMC colonic transit time (CTT). T-tests with bonferroni correction compared contractility parameters between subjects and between baseline and post-wake. Results A total of 24 healthy and 21 constipated subjects were analyzed, of which 9 were NTC and 12 were STC. Healthy subjects had 29 wake events and constipated subjects had 43 wake events (12 in NTC and 31 in STC). Average CTT was 1654 minutes for healthy, 2492 minutes for NTC and 5781 minutes for STC. After wakening, healthy, NTC, and STC subjects showed increased absolute contractility parameters (Ct, AUC, and MI) compared to baseline in all post-wake windows (p < 0.01). Contractile parameters (Ct, AUC, and MI) were significantly decreased in STC versus healthy subjects in the immediate 20 minutes after wake (p < 0.001). (Fig 1) Conclusion WMC is able to capture diurnal variation in colonic contractile activity. NTC and STC subjects have an intact increase in contractility parameters (Ct, AUC, and MI) upon wake as in healthy subjects. However, in the STC subset these contractility parameters are significantly decreased in the immediate 20 minutes after wake compared to healthy controls indicating a blunted response. This may suggest some unique neuropathic process contributing to STC.
BACKGROUND: Difficulty with evacuation is a common clinical problem after spinal cord injury (SCI) and other disorders characterized by constipation. Our group reported that intravenous (IV) administration of neostigmine and glycopyrrolate (NEO/GLY) safely and rapidly promotes bowel evacuation (AJG, 100:1560,2005). Because IV administration of these agents is of limited practical value for routine bowel care, a non-parenteral approach to drug delivery was investigated. Iontophoretic (ION) technology that employs an electric field to non-invasively drive polar ions across the skin was tested as a viable drug delivery approach to achieve safe, predictable bowel evacuation. AIMS: To determine whether transdermal (TD) administration of NEO/GLY by ION technology: 1) promotes increased bowel motility and evacuation and 2) has an acceptable safety profile. METHODS: The ION system consisted of Dynatron iBoxes™ delivered a positive current of 4.0 mA-min x 10 min via a dermal patch. Those with a history of cardiovascular or pulmonary complications were excluded from the study. At Visit 1, subjects were screened for responsiveness to IV NEO (0.03 mg/kg)/GLY (0.006 mg/kg). Those with a positive response to IV NEO/GLY progressed to Visit 2 to receive low-dose TD NEO (0.05 mg/kg)/GLY (0.01 mg/kg). Those who failed to have drug-related symptoms and/or a bowel movement after administration of low-dose TD NEO/GLY were administered high-dose TD NEO (0.07 mg/kg)/GLY (0.014 mg/kg) at Visit 3. After TD drug administration, defecation, increased bowel sounds, and other cholinergic side effects were assessed every 5 min for 1 hour. RESULTS: 23 subjects were screened with IV NEO/GLY; 17 of 23 subjects had a bowel movement (21±23 min); 22 of 23 subjects reported drug-related side effects (i.e., presence of eye twitching, cramping, and/ or defecation). 20 subjects who reported a positive drug-related response after IV NEO/GLY progressed to Visit 2; after low-dose TD NEO/GLY, 5 of 20 subjects (25%) had bowel evacuation (36±15 min), and 12 subjects (60%) had drug-related responses. 14 subjects who did not have cholinergic responses at Visit 2 then progressed to receive a higher dose of TD NEO/GLY at Visit 3; 5 of 14 subjects (35.7%) had bowel evacuation (26±22min) and 12 (85.7%) had drug-related responses. Overall, 50% of subjects had bowel evacuations with either low-or high-dose TD NEO/GLY. Cardiopulmonary measurements were not clinically altered during any of the study visits. No statistical differences were observed in bowel evacuation time between IV screening vs. either low-dose (p=0.10) or high-dose (p= 0.68) TD NEO/GLY. CONCLUSIONS: TD NEO/GLY may be safely administered by ION to induce increased bowel motility and evacuation. Thus, TD NEO/GLY may improve bowel care in persons with SCI and, perhaps, other conditions characterized by prolonged colonic transit time.
Su1588 Prevalence and Risk Factors of Overlaps Between GERD-Constipation and Constipation-GERD Gabriela Rojas-Loureiro, Ilce Belinda Lazaro Pacheco, Ricardo Flores Rendon, Maria Eugenia Icaza-Chávez, Octavio Gomez-Escudero, Enrique Coss-Adame, Mercedes AmievaBalmori, Olivia Rascon Sosa, Jose M. Remes Troche Introduction: Overlap between different functional gastrointestinal disorders is very common. Several studies have shown that irritable bowel syndrome (IBS), functional dyspepsia (FD) and gastroesophageal reflux disease (GERD) frequently overlaps. Constipation symptoms may affect up to 14 to 22% of the general population, while about 12-15% may suffer of GERD symptoms least 1 time per week (Remes-Troche DDW 2014), so it is logical to think that these entities may alsooverlaps. However, searching in the literature we did not found evidence regarding the overlap between GERD-Constipation or Constipation-GERD symptoms. Aim: To evaluate prevalence and risk factors associated to the overlap between GERD and Constipation and vice versa Materials and Methods: A prolective, cross-sectional study was conducted including consecutive subjects who attended to five third referral centers because the presence of symptoms of GERD and / or constipation. Diagnosis of GERD was done according to the presence of typical symptoms (heartburn and regurgitation) but also using the Carlsson-Dent questionnaire (> 4 points was considered as positive). Constipation symptoms were evaluated using the Rome III criteria for IBS-C, functional constipation (FC) and dyssynergic defecation (DD). Demographic characteristics and factors associated with both conditions were analyzed Results: 324 patients were included, 250 were women (77%) with amean age of 46 ± 16 years. Of these, 206 (64%) attended for GERD and 118 (36%) for constipation symptoms. Among GERD patients, 152 (72%) were women (mean 44.8 ± 14 years) and the overlap with constipationwas 40% (n = 83). Forty had IBS-C, 40 FC and 3 DD. Patients with GERD-Constipation were older (48 ± 14 vs 42 ± 15, p = 0.002). Risk factors for this overlap were female gender (OR = 1.48) and obesity (OR = 2.091). Interestingly, GERD-Constipationpatients reported greater improvement using PPIS compared to patients with only GERD (p = 0.23, OR = 0.379). Among patients who attended for constipation (n=118) (98 women, mean age 48.5 ± 17 years) 71 (62.3%) had IBS-C, 33 (28.9%) had FC, 10 (8.8%) DD and 4 were unclassified. In constipation patients overlapping with GERD was 56% (n = 64). Risks factors for Constipation-GERD were obesity (OR 1.38) and the presence of excessive pushing (RM 2.86). Conclusions: ConstipationGERD overlap more often than GERD-Constipation. However in both groups obesity is an
Figure 1. Contractility response to wake in healthy, normal transit constipation, and slow transit constipation as compared to baseline windows (* p < 0.01). STC compared to healthy subjects showed significantly decreased Ct immediately after waking (p < 0.001).
Su1590 Factors Associated With the Use of Laxatives in the United States Adult Population Shuji Mitsuhashi, Zhenghui G. Jiang, Judy W. Nee, Mohammed Zakari, Anthony Lembo Background: Constipation is one of the most common gastrointestinal complaints in an ambulatory setting. Laxatives, treatments for constipation, are readily accessible. However, the prevalence and determinants of laxative use in the community is not well understood. We sought to describe the prevalence and factors associated with laxative use in a cohort representative of the US adult population. Method: Using data from the 2009-2010 National Health and Nutrition Examination Surveys (NHANES), the use of laxatives was identified from the questionnaire on bowel health provided by 6,059 study subjects enrolled. We investigated potential factors that are associated with laxative use, including demographics, medical history, bowel health, and socio-economic status. Their relationships with laxative use were studied by both univariate and multivariate regression models adjusting for sampling weights that reconstituted the US population. Results: Among the US adult population age
S-535
X : 10052$CH01 03-28-16 00:57:27 PDFd : 10052B : o
Page 535
AGA Abstracts
AGA Abstracts
CI=confidence interval; CIC=chronic idiopathic constipation. *N=302, 122, 118 and 62 for patients receiving placebo in the pooled population and Studies 1, 2 and 3, respectively. † N=301, 120, 119 and 62 for patients treated with lubiprostone in the pooled population and Studies 1, 2 and 3, respectively. ‡Stool consistency responders: 1-unit improvement from baseline on a 5- or 7-point scale each week for ‡3 of 4 treatment weeks. **Straining responders: 1-unit improvement from baseline on a 5-point scale each week for ‡3 of 4 treatment weeks.