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415 Small Bowel Dysmotility Is Significantly Associated With Small Intestinal Bacterial Overgrowth (SIBO) As Measured by a Wireless Motility Capsule
incidence of overt UGIB has steadily decreased, that of occult GIB continued to rise. Over the same period, there was a significant rise in the use of NSAIDs (mainly non-selective compounds), PPIs and iron therapy. Demography: Compared with patients with occult GIB (N=300) randomly selected in the 3 index years, those with overt UGIB (N=869) had a median (IQR) age of 63 (47-77) years vs. 67 (53-75) in the occult group (NS), 62.5 % males vs. 39.3% (P<0.001), 33.3 % smokers vs. 28.0 % (NS), and 25.0 % excessive alcohol drinkers vs. 11.0 % (P<0.001), respectively. Both groups were comparable in the use of NSAIDs and ATT, but overt UGIB patients had higher Charlson comorbidity scores, 2 (13) vs. 1 (0-2) (P<0.001). Transfusion and 30-day mortality: 3.8 % in the overt UGIB group died vs. 3.0 % (NS) in the occult group, and 34.3 % vs. 13.0 % (P<0.001) were transfused with 3 (2-6) blood units vs. 2.5 (2-4) (P=0.024), respectively in the occult GIB group. CONCLUSIONS: (1) The incidence of occult GIB continues to rise while that of overt UGIB continues to fall. (2) This is accompanied by a rise in the use of NSAIDs, PPIs, and iron therapy. (3) Patients with occult GIB have similar 30-day mortality to overt UGIB but are less likely to require blood transfusion. (4) An alternative approach to acid inhibition might be needed to prevent occult GIB. Table 1. The incidence of Overt UGIB vs. Occult GIB and Details of Drug Use. P-values refer to trend with time.
413 Comparison of In-Hospital Mortality of Conservative Versus Surgical Management of Peptic Ulcer Perforation in US Hospitals. Is Conservative Management Deadly? Firew M. Wubiee, Belen A. Tesfaye, Angesom Kibreab, Charles D. Howell Background: With the advent of effective therapy for H. Pylori and use of Proton pump inhibitors and H2 blockers; there is an increase in the trend of conservative management of peptic ulcer perforation. Although some studies suggest that conservative management is a viable alternative, there is limited data on mortality benefits. Aim: To compare inhospital mortality, length of stay and cost of care of patients admitted for peptic ulcer disease perforation when managed conservatively versus surgically. Methods: We used the weighted Nationwide Inpatient Sample data from 2000 to 2011 for our study. Cases were identified using ICD 9 codes. A total of 1809 cases with a documented perforated peptic ulcer disease in their first three discharge diagnoses are included in the study. The main outcome variables were inpatient mortality, length of hospital stay and cost of healthcare delivery. Result: Conservative management was preferred in 69% of the cases and 31% received surgical intervention (laparoscopic or open abdominal surgery). The conservative group was older (Mean age 67.8 versus 60.7 years, P < 0.01), female predominant (P=0.03), and had higher prevalence of coronary artery disease (P <0.005), dyslipidemia (P < 0.001) and hypertension (P <0.01). On the other hand, blood transfusion (P<0.01), smoking (P < 0.01), cirrhosis (P < 0.01), diabetes mellitus (p=0.01) and alcohol ingestion (P <0.01) were most common in the surgical intervention group. No significant difference was noted in obesity (P = 0.82), and congestive heart failure (P = 0.36). Patients in the surgical intervention group stayed nearly twice as long in the hospital (Length of Stay 6.2 days versus 11.7 days, P < 0.01) and cost twice as much in health care delivery (US $ 31,721 versus US $ 61,760, P < 0.01) than the conservative management group. There was a 41% reduction in mortality in the surgical intervention group than the conservative management group. When adjusted for comorbid conditions, the mortality benefit reduced to 36 % but the difference remained statistically significant (Table). Blacks were twice as likely to get conservative therapy than any other group (P< 0.01) but the mortality difference was not statistically significant. Patients with diabetes mellitus (OR= 2.2, 95% CI 1.4-3.5), dyslipidemia (OR=2.3, 95% CI 1.4 - 3.6) history of smoking (OR=3.3, 95 % CI 1.6 -6.5) and age 65 years and above (OR= 2.0, 95% CI 1.3-3.2) had increased mortality regardless of the treatment groups they are assigned. Conclusion: Surgical management of perforated peptic ulcer disease has significantly reduced in-hospital mortality rate than conservative management. Blacks are disproportionately managed conservatively than any other group. Comparison of in-hospital mortality among patients managed surgically and conservatively for peptic ulcer perforation
415 Small Bowel Dysmotility Is Significantly Associated With Small Intestinal Bacterial Overgrowth (SIBO) As Measured by a Wireless Motility Capsule Bani Chander Roland, Xi E. Zheng, Ahmed E. Salem, Eric Tomakin, Gerard E. Mullin, Pankaj J. Pasricha Background: Small Intestinal Bacterial Overgrowth (SIBO) is a significant and increasingly recognized clinical syndrome. Although the manifestations can be severe, SIBO is most often suspected in patients with non-specific symptoms such as abdominal discomfort, bloating & diarrhea. Altered small intestinal motility is thought to contribute to the development of SIBO. However, further study has been limited by technical challenges & lack of availability of antroduodenal manometry. Using a wireless motility capsule (WMC), we hypothesized that patients with SIBO would have prolonged small bowel transit time as compared to those without. Aims: The aims of this study were to prospectively: 1) Assess the relationship between small bowel transit time (SBTT) by WMC testing & presence of SIBO defined as positive lactulose hydrogen breath test (LBT); 2) Assess the relationship of gastric (GET), colonic (CTT) & whole gut transit (WGTT) times with LBT positivity; 3) Evaluate gastric & small bowel pH in relationship with LBT. Methods: A prospective study of 30 consecutive patients with suspected SIBO who were referred for motility testing at a tertiary care center from 3/2014-9/2014. All underwent WMC & LBT testing. Clinical & demographic characteristics were compared. Gastric, small bowel, colonic, & whole gut transit times were measured & correlated with LBT results. Gastric/small bowel pH measurements were also obtained & compared. All WMC tests were interpreted by a single, blinded reader. Results: Of the 28 patients who completed both WMC and LBT, 15 (53.6%) had +LBT. There were no significant clinical or demographic differences between the LBT + and - groups. The mean SBTT among those with +LBT was 8.19h vs 3.18 h in -LBT (p=<0.01). Prolonged SBTT (>6 hr) was present in 53.9% of patients with +LBT while in 0% of those with -LBT (p=0.002). There were no significant differences between the two groups in regards to gastric, colonic or whole gut transit times [GET: + LBT 3.95hr vs -LBT =3.19hr, p=0.15, CTT: +LBT= 41.21h vs -LBT= 35.97h, p= 0.4; WGTT: +LBT= 57.1h vs -LBT: 43.2h p= 0.06]. Gastric (3.6 vs 2.4, p< 0.01) & SB pH (7.0 vs 6.6, p= 0.05) were significantly higher in +LBT vs -LBT. Conclusions: Patients with SIBO have significant delays in SBTT, suggesting small bowel dysmotility may be an important player in the development of SIBO. These patients interestingly do not have evidence of delayed gastric emptying or prolonged transit times in other areas of the gut. These patients also have higher gastric & small bowel pH, suggesting that higher pH may also predispose to SIBO development. Measuring SBTT & intestinal pH by a simple, non-invasive approach may be useful in patients with suspected SIBO. Additionally, identification of specific pathophysiological defects in this population may guide therapeutic options for those refractory to standard therapy.
*Adjusted for age, sex, race, CHF, CAD, Cirrhosis, Blood transfusion, HTN, DM, dyslipidemia, Smoking, and obesity
414 Occult vs. Overt Upper Gastrointestinal Bleeding - Inverse Relationship and the Use of Mucosal Damaging and Protective Drugs Ali S. Taha, Caroline McCloskey, Theresa Craigen, Annette J. Simpson, Wilson J. Angerson
416
Efforts have been focused on the prevention of overt upper gastrointestinal bleeding (UGIB), using acid inhibitors, particularly in users of NSAIDs and anti-thrombotic therapy (ATT). Little is known about the impact of such efforts on occult GIB which might also originate from sites not protected by acid inhibition. We aimed to measure the incidence of both overt and occult GIB in a well-defined geographical region over a 5-year period, 2007-2012; assess the use of NSAIDs, ATT, proton pump inhibitors (PPIs), and iron therapy; and compare the clinical details and outcomes of patients with occult vs. overt GIB. METHODS: The incidence (number of cases per 100, 000 population per annum) was analyzed in 2007, 2010 and 2012. Overt UGIB included hematemesis and melena. Occult GIB refers to iron deficiency anemia in the absence of overt UGIB, frank rectal bleeding, dietary insufficiency, malabsorption, and known neoplasia or bowel diseases. A sample of 300 patients (100 from each of the 3 index years) with occult GIB was randomly selected and their outcomes and details were compared with those of patients with overt UGIB (N=869) using the MannWhitney and Fisher's exact tests. Trends with time in incidence were assessed using the chi-squared test for trend. Numbers of prescriptions issued per 1000 population were recorded for each year from 2007 to 2012 and trends were assessed using Pearson correlation analysis. RESULTS: The incidence and details of drug use are shown in Table 1. While the
Live but Not Killed Sulfate-Reducing Bacteria Slow Intestinal Transit in a Bismuth-Reversible Fashion in Mice Nathaniel Ritz, Benjamin Burnett, Larry L. Barton, Melissa Wilson, Sudha B. Singh, Henry C. Lin Background: Hydrogen Sulfide (H2S) inhibited spontaneous motor activity of intestinal muscle strips when introduced via the H2S donor sodium hydrosulfide (Neurogastroenterol Motil. 2008;12:1306-1316). Endogenous H2S generated by the intestinal muscle layer exerted a hyperpolarizing effect on colonic smooth muscle cells (J Physiol 2014;592 (Pt 5):1077-89). The intestine is also exposed to a second source of H2S as bacteria-derived H2S is generated by sulfate-reducing bacteria (SRB) when these microbes convert hydrogen produced during bacterial fermentation to H2S. However, the effect of bacteria-derived H2S on intestinal transit in whole animals is not known. Bismuth subsalicylate is a compound that binds H2S. Treating healthy human subjects with this compound reduced fecal release of H2S by > 95% (Gastroenterology 1998;114(5):923-9 ). Aim: The aim of this study was to test the hypothesis that intestinal transit may be slowed by sulfate-reducing bacteria in
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comparable among treatment groups. In the L15, V10 and V20 groups, respectively, incidences of serious TEAEs were 8.6%, 8.3% and 14.2%, and of TEAEs leading to study drug discontinuation were 7.6%, 4.1% and 12.7%. Serum gastrin increased at Week 4 in all treatment groups, followed by a moderate increase until Week 52. Pepsinogen I and II increased at Week 4 in all treatment groups, then remained at a stable level until Week 52. There were no clinically significant changes in laboratory tests and vital signs pre- and posttreatment for any treatment group. Recurrence rates of peptic ulcer for L15, V10 and V20 groups, respectively, were 7.0%, 3.8%, and 5.4% at Week 52, and 7.5%, 3.8%, and 5.9% at Week 76 and Week 104. Conclusion: The long-term safety profile of V10 and V20 was similar to that of L15 with no safety issues identified. VPZ 10 mg and 20 mg were highly effective for prevention of peptic ulcer recurrence during NSAID therapy and this effect was maintained during long-term use.
413 Comparison of In-Hospital Mortality of Conservative Versus Surgical Management of Peptic Ulcer Perforation in US Hospitals. Is Conservative Management Deadly? Firew M. Wubiee, Belen A. Tesfaye, Angesom Kibreab, Charles D. Howell Background: With the advent of effective therapy for H. Pylori and use of Proton pump inhibitors and H2 blockers; there is an increase in the trend of conservative management of peptic ulcer perforation. Although some studies suggest that conservative management is a viable alternative, there is limited data on mortality benefits. Aim: To compare inhospital mortality, length of stay and cost of care of patients admitted for peptic ulcer disease perforation when managed conservatively versus surgically. Methods: We used the weighted Nationwide Inpatient Sample data from 2000 to 2011 for our study. Cases were identified using ICD 9 codes. A total of 1809 cases with a documented perforated peptic ulcer disease in their first three discharge diagnoses are included in the study. The main outcome variables were inpatient mortality, length of hospital stay and cost of healthcare delivery. Result: Conservative management was preferred in 69% of the cases and 31% received surgical intervention (laparoscopic or open abdominal surgery). The conservative group was older (Mean age 67.8 versus 60.7 years, P < 0.01), female predominant (P=0.03), and had higher prevalence of coronary artery disease (P <0.005), dyslipidemia (P < 0.001) and hypertension (P <0.01). On the other hand, blood transfusion (P<0.01), smoking (P < 0.01), cirrhosis (P < 0.01), diabetes mellitus (p=0.01) and alcohol ingestion (P <0.01) were most common in the surgical intervention group. No significant difference was noted in obesity (P = 0.82), and congestive heart failure (P = 0.36). Patients in the surgical intervention group stayed nearly twice as long in the hospital (Length of Stay 6.2 days versus 11.7 days, P < 0.01) and cost twice as much in health care delivery (US $ 31,721 versus US $ 61,760, P < 0.01) than the conservative management group. There was a 41% reduction in mortality in the surgical intervention group than the conservative management group. When adjusted for comorbid conditions, the mortality benefit reduced to 36 % but the difference remained statistically significant (Table). Blacks were twice as likely to get conservative therapy than any other group (P< 0.01) but the mortality difference was not statistically significant. Patients with diabetes mellitus (OR= 2.2, 95% CI 1.4-3.5), dyslipidemia (OR=2.3, 95% CI 1.4 - 3.6) history of smoking (OR=3.3, 95 % CI 1.6 -6.5) and age 65 years and above (OR= 2.0, 95% CI 1.3-3.2) had increased mortality regardless of the treatment groups they are assigned. Conclusion: Surgical management of perforated peptic ulcer disease has significantly reduced in-hospital mortality rate than conservative management. Blacks are disproportionately managed conservatively than any other group. Comparison of in-hospital mortality among patients managed surgically and conservatively for peptic ulcer perforation
415 Small Bowel Dysmotility Is Significantly Associated With Small Intestinal Bacterial Overgrowth (SIBO) As Measured by a Wireless Motility Capsule Bani Chander Roland, Xi E. Zheng, Ahmed E. Salem, Eric Tomakin, Gerard E. Mullin, Pankaj J. Pasricha Background: Small Intestinal Bacterial Overgrowth (SIBO) is a significant and increasingly recognized clinical syndrome. Although the manifestations can be severe, SIBO is most often suspected in patients with non-specific symptoms such as abdominal discomfort, bloating & diarrhea. Altered small intestinal motility is thought to contribute to the development of SIBO. However, further study has been limited by technical challenges & lack of availability of antroduodenal manometry. Using a wireless motility capsule (WMC), we hypothesized that patients with SIBO would have prolonged small bowel transit time as compared to those without. Aims: The aims of this study were to prospectively: 1) Assess the relationship between small bowel transit time (SBTT) by WMC testing & presence of SIBO defined as positive lactulose hydrogen breath test (LBT); 2) Assess the relationship of gastric (GET), colonic (CTT) & whole gut transit (WGTT) times with LBT positivity; 3) Evaluate gastric & small bowel pH in relationship with LBT. Methods: A prospective study of 30 consecutive patients with suspected SIBO who were referred for motility testing at a tertiary care center from 3/2014-9/2014. All underwent WMC & LBT testing. Clinical & demographic characteristics were compared. Gastric, small bowel, colonic, & whole gut transit times were measured & correlated with LBT results. Gastric/small bowel pH measurements were also obtained & compared. All WMC tests were interpreted by a single, blinded reader. Results: Of the 28 patients who completed both WMC and LBT, 15 (53.6%) had +LBT. There were no significant clinical or demographic differences between the LBT + and - groups. The mean SBTT among those with +LBT was 8.19h vs 3.18 h in -LBT (p=<0.01). Prolonged SBTT (>6 hr) was present in 53.9% of patients with +LBT while in 0% of those with -LBT (p=0.002). There were no significant differences between the two groups in regards to gastric, colonic or whole gut transit times [GET: + LBT 3.95hr vs -LBT =3.19hr, p=0.15, CTT: +LBT= 41.21h vs -LBT= 35.97h, p= 0.4; WGTT: +LBT= 57.1h vs -LBT: 43.2h p= 0.06]. Gastric (3.6 vs 2.4, p< 0.01) & SB pH (7.0 vs 6.6, p= 0.05) were significantly higher in +LBT vs -LBT. Conclusions: Patients with SIBO have significant delays in SBTT, suggesting small bowel dysmotility may be an important player in the development of SIBO. These patients interestingly do not have evidence of delayed gastric emptying or prolonged transit times in other areas of the gut. These patients also have higher gastric & small bowel pH, suggesting that higher pH may also predispose to SIBO development. Measuring SBTT & intestinal pH by a simple, non-invasive approach may be useful in patients with suspected SIBO. Additionally, identification of specific pathophysiological defects in this population may guide therapeutic options for those refractory to standard therapy.
*Adjusted for age, sex, race, CHF, CAD, Cirrhosis, Blood transfusion, HTN, DM, dyslipidemia, Smoking, and obesity
414 Occult vs. Overt Upper Gastrointestinal Bleeding - Inverse Relationship and the Use of Mucosal Damaging and Protective Drugs Ali S. Taha, Caroline McCloskey, Theresa Craigen, Annette J. Simpson, Wilson J. Angerson
416
Efforts have been focused on the prevention of overt upper gastrointestinal bleeding (UGIB), using acid inhibitors, particularly in users of NSAIDs and anti-thrombotic therapy (ATT). Little is known about the impact of such efforts on occult GIB which might also originate from sites not protected by acid inhibition. We aimed to measure the incidence of both overt and occult GIB in a well-defined geographical region over a 5-year period, 2007-2012; assess the use of NSAIDs, ATT, proton pump inhibitors (PPIs), and iron therapy; and compare the clinical details and outcomes of patients with occult vs. overt GIB. METHODS: The incidence (number of cases per 100, 000 population per annum) was analyzed in 2007, 2010 and 2012. Overt UGIB included hematemesis and melena. Occult GIB refers to iron deficiency anemia in the absence of overt UGIB, frank rectal bleeding, dietary insufficiency, malabsorption, and known neoplasia or bowel diseases. A sample of 300 patients (100 from each of the 3 index years) with occult GIB was randomly selected and their outcomes and details were compared with those of patients with overt UGIB (N=869) using the MannWhitney and Fisher's exact tests. Trends with time in incidence were assessed using the chi-squared test for trend. Numbers of prescriptions issued per 1000 population were recorded for each year from 2007 to 2012 and trends were assessed using Pearson correlation analysis. RESULTS: The incidence and details of drug use are shown in Table 1. While the
Live but Not Killed Sulfate-Reducing Bacteria Slow Intestinal Transit in a Bismuth-Reversible Fashion in Mice Nathaniel Ritz, Benjamin Burnett, Larry L. Barton, Melissa Wilson, Sudha B. Singh, Henry C. Lin Background: Hydrogen Sulfide (H2S) inhibited spontaneous motor activity of intestinal muscle strips when introduced via the H2S donor sodium hydrosulfide (Neurogastroenterol Motil. 2008;12:1306-1316). Endogenous H2S generated by the intestinal muscle layer exerted a hyperpolarizing effect on colonic smooth muscle cells (J Physiol 2014;592 (Pt 5):1077-89). The intestine is also exposed to a second source of H2S as bacteria-derived H2S is generated by sulfate-reducing bacteria (SRB) when these microbes convert hydrogen produced during bacterial fermentation to H2S. However, the effect of bacteria-derived H2S on intestinal transit in whole animals is not known. Bismuth subsalicylate is a compound that binds H2S. Treating healthy human subjects with this compound reduced fecal release of H2S by > 95% (Gastroenterology 1998;114(5):923-9 ). Aim: The aim of this study was to test the hypothesis that intestinal transit may be slowed by sulfate-reducing bacteria in
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comparable among treatment groups. In the L15, V10 and V20 groups, respectively, incidences of serious TEAEs were 8.6%, 8.3% and 14.2%, and of TEAEs leading to study drug discontinuation were 7.6%, 4.1% and 12.7%. Serum gastrin increased at Week 4 in all treatment groups, followed by a moderate increase until Week 52. Pepsinogen I and II increased at Week 4 in all treatment groups, then remained at a stable level until Week 52. There were no clinically significant changes in laboratory tests and vital signs pre- and posttreatment for any treatment group. Recurrence rates of peptic ulcer for L15, V10 and V20 groups, respectively, were 7.0%, 3.8%, and 5.4% at Week 52, and 7.5%, 3.8%, and 5.9% at Week 76 and Week 104. Conclusion: The long-term safety profile of V10 and V20 was similar to that of L15 with no safety issues identified. VPZ 10 mg and 20 mg were highly effective for prevention of peptic ulcer recurrence during NSAID therapy and this effect was maintained during long-term use.