- Email: [email protected]
Mo1654 FODMAPs: Fermentation and Symptom Severity in Functional Gastrointestinal Disorders
AGA Abstracts
on gastrointestinal motility and symptoms in patients with IBS and healthy volunteers (HV). Methods: We recruited patients with IBS based on ROME III criteria. Celiac disease was excluded by a negative IgA TG2 antibody test and duodenal biopsy (Marsh 0-I). HLA-DQ2/ DQ8 status was determined but was not an inclusion criterion. IBS patients were stratified according to their anti-gliadin antibody (AGA) status. A cohort of healthy volunteers (HV) was used as control. Symptoms and gastrointestinal (GI) transit were studied before and after 1-month of GFD. GI transit was evaluated by modified SHAPE study. We assessed gut symptoms (Birmingham, Bristol scale and GSRS), anxiety and depression (HADs), somatic symptoms (PHQ-15) and dietary habits (DQESV2). Fecal microbiota was analysed by 16S rRNA-based Illumina. GFD instructions and compliance were assessed by a trained dietitian. Results : Thirty five IBS patients (15 AGA+ and 20 AGA-) and 26 healthy volunteers were enrolled. Compared to HV, GI transit normalized after GFD in 42% of IBS AGA+ patients vs 25% in IBS AGA- patients. Overall GI symptoms, particularly indigestion (p=0.02), diarrhea (p=0.008) and abdominal pain (p=0.005) improved after GFD in the IBS AGA+ patients but there were no changes in GI symptoms in IBS AGA- patients. Similarly, depression scores decreased in IBS AGA+ but not in IBS AGA- patients. Overall wellbeing, especially positivity (p=0.007) and vitality (p=0.02), improved in IBS AGA+ but not in IBS AGApatients. Individual shifts in microbiota profiles, with overall mild decrease in Firmicutes/ Bacteroidetes ratio was observed in the IBS AGA+ patients. GFD diet had overall no effect in healthy volunteers, although some of them developed constipation. Conclusions: The results suggest that the stratification by anti-gliadin antibody status can identify a subgroup of IBS patients that respond symptomatically to GFD. The gluten-free diet does not seem to improve GI symptoms, overall wellbeing or gut function in IBS patients without AGA.
to be the best treatment as compared to placebo [OR = 6.14, 95% C.I. (2.81 - 13.41)]. RTT was a close second as compared to placebo [OR = 6.08, 95% C.I. (2.01 - 18.37)] (Figure 2). Between pharmacological treatments, TCAs were the best drugs for management as compared to placebo [OR = 4.08 (2.13, 7.84)] and SSRIs were also found to be effective as compared to placebo 2.54 (1.09, 5.94). CBT was also superior to Probiotics [OR = 2.65 (1.08, 6.55)] but not superior to hypnotherapy, MCPT or RTT. Similarly, TCAs were not superior to SSRIs in treatment of IBS. Imprecise estimates and the small number of direct trials lowered our confidence in several comparisons. CONCLUSIONS: In patients with IBS, the best therapy is non-pharmacological, CBT followed by RTT. Between pharmacological therapies, TCAs were better than placebo but not superior to SSRIs.
Mo1654 FODMAPs: Fermentation and Symptom Severity in Functional Gastrointestinal Disorders Juan S. Lasa, Pablo A. Olivera, Guillermo Dima, Angel D. Peralta, Robert Prizont, Luis O. Soifer
Network of included studies .
Background: The use of reduced amounts of food with oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) has shown to be an effective measure to reduce symptom severity in patients with functional gastrointestinal disorders (FGD). However, not all patients could make an association between ingested dietary FODMAP and worsening of their symptoms. Aim: To compared symptom severity and degree of fermentation between patients with FGD in whom FODMAP foods worsened their symptoms, and FGD patients in whom FODMAP foods did not worsen their symptoms. Patients and Methods. A group of 147 patients with FGD (125 women, mean age 50 y) classified according to the Rome III Criteria as Irritable Bowel Syndrome (IBS), CFAB and chronic abdominal pain (AP). Patients were consecutively studied and included 65 IBS/Diarrhea (IBS/D), 39 IBS/Constipation (IBS/C), 14 with mix constipation and diarrhea (IBC/CD), 27 CFAB and 2 AP. Fermentation was evaluated by the breath hydrogen (H2) test. At baseline and after ingestion of 10g lactulose, H2 concentration in expired air was measured for 3 hours with sampling every 20 minutes. A fermentative profile (FP) was developed by calculating the area under the curve of H2 concentration/time. All subjects completed two questionnaires, the first referred to the clinical characteristics of patients and foods that aggravate their symptoms and the second referred to the symptom severity score (SSS), the estimation of the overall symptom severity (OSS), abdominal pain (AP), subjective abdominal bloating (BLO), evacuation disturbance (EVAC) and the degree of symptom interference with daily activities (IDA). A two tail t-test was used for statistical comparison between the two groups; significance was set at p<0.05. Results. Overall, 111 subjects (76 % of the total group) reported worsened symptoms by dietary FODMAPs whereas 36 could not established a link between FODMAPs and digestive symptoms. With the exception of EVAC, all reported scale variables of symptom severity (SSS, OSS, AP) were statistically significantly higher in IBS, CFAB, AP patients who reported worsened symptoms by ingestion of dietary FODMAPS. By contrast, there was no difference in the FP between IBS, CAB, AP patients worsened by FODMAPs and FGD patients in whom symptoms were unaltered by FODMAPs. Conclusions. This case-control-study in FGD patients showed a strong relationship between severity of abdominal symptoms associated to FODMAPs as measured by validated scales and a positive history of symptom aggravation induced by these dietary sugars, oligosaccharides and polyols. The increase in symptom severity was not associated to an increase in expired breath H2 and FP suggesting that an increase in H2 by the colon microbiota may not be responsible for the symptom severity associated with FODMAPs
Pooled Summary Estimates From Indirect Estimates and Network Meta-Analysis Informing on Comparative Efficacy of interventions for IBS symptoms improvement
Mo1656 Outcomes of Fidaxomicin Treatment of Clostridium difficile Infection Clayton M. Spiceland, George Saffouri, Darrell Pardi, Sahil Khanna PURPOSE: Fidaxomicin is a narrow spectrum antibiotic used for the treatment of Clostridium difficile infection (CDI). We evaluated response and recurrence rates of CDI after treatment with fidaxomicin. METHODS: All cases of CDI treated with fidaxomicin at 3 referral centers over a 4 year period were identified using the electronic medical record. Inclusion criteria included a definite CDI diagnosis (3 or more episodes of watery diarrhea in a 24-hour period and positive Clostridium difficile stool assay) and treatment with fidaxomicin 200 mg twice daily for 10 days. Response was defined as resolution of diarrhea. Recurrence was defined if, after symptom resolution, CDI diagnostic criteria were met within 8 weeks of initial diagnosis. Diarrhea recurring after 8 weeks of resolution was considered a new episode. All patients had at least 8 weeks of follow up. Data collected included demographics, number of prior CDI episodes, prior CDI treatment, response to fidaxomicin, recurrence, and adverse effects. RESULTS: 81 patients with median age 56 years; 53% female; 26% with inflammatory bowel disease (IBD) were identified. Most patients (75%) had prior episodes of CDI with a median of 2 previous episodes (range 0 to 8). 90% and 89% were treated with one or more courses of metronidazole and vancomycin respectively; 5 patients had prior fecal transplantation. Complete response occurred in 73 patients (90%) while 8 (10%) had no response; 19% of responders had recurrent CDI. Responders had fewer prior episodes of CDI (median 1, range 0 to 8), compared to non-responders (median 2.5, range 1 to 8), p= 0.01. Responders who did not recur had fewer prior episodes of CDI (median 1, range 06) than patients who recurred (median 2, range 1 to 8), p=0.005. The rate of response in patients with a first episode (n=20) was 100%, compared to 95% in patients with one prior episode (n=22/23) and 82% in patients with 2 or more episodes (n=31/38), p=0.02. Of responders, the rates of recurrent CDI in patients with a first episode was 0%, compared to 23% in patients with one prior episode and 29% in patients with 2 or more episodes, p=0.005. All patients with IBD (n=21) responded to fidaxomicin, with 19% experiencing recurrence. There were no adverse events reported with fidaxomicin. CONCLUSION: In the largest post-clinical trial study of fidaxomicin, we demonstrate that fidaxomicin is effective in treating CDI in clinical practice, including patients with recurrent infection and IBD. All patients treated with fidaxomicin for a first episode of CDI responded with no recurrences. Patients with one or more prior CDI episodes were less likely to respond and more likely to recur suggesting that fidaxomicin use early in CDI course may be more beneficial than later use.
Mo1655 Effectiveness of Pharmacological and Non-Pharmacological Therapies for Irritable Bowel Syndrome: A Systematic Review and Bayesian Network MetaAnalysis Sushil Kumar Garg, Vaibhav Wadhwa, Chimaobi M. Anugwom, Nancy Gupta, John George, Madhusudhan R. Sanaka, Shahnaz Sultan BACKGROUND/AIMS: Few head-to-head trials have been conducted comparing pharmacological with non-pharmacological therapies for Irritable Bowel Syndrome. The objective of this study was to perform a Bayesian network meta-analysis combining direct and indirect treatment comparisons to assess the comparative effectiveness of pharmacological and nonpharmacological treatments for IBS. METHODS: We conducted a systematic literature review in Medline (1946-October 2015), EMBASE (1974-October 2015), and the Cochrane controlled trials registry for randomized controlled trials of adults with IBS. Specifically, we included the trials that compared the efficacy of active interventions [Selective serotonin reuptake inhibitors (SSRIs), Tricyclic Antidepressants (TCAs), cognitive behavioral therapy (CBT), multicomponent psychodynamic therapy (MCPT), relaxation training therapy RTT), hypnotherapy, fiber diet (bran and ispaghula) and probiotics) with each other or placebo on improving IBS symptoms. We performed both direct and Bayesian network meta-analysis for all treatments. The primary outcome of our network meta-analysis was failure in improvement in IBS symptoms (as defined by the individual studies). RESULTS: We included 72 randomized controlled trials consisting of total 5832 patients comparing 10 different interventions (Figure1). In non-pharmacological interventions for IBS, CBT was considered
AGA Abstracts
Mo1657 Lactulose and the Risk of Clostridium difficile-Infection in Decompensated Cirrhosis Anant Agarwalla, Andrew Rhim, Andrew T. Weber, Sonya Davey, David S. Goldberg, YuXiao Yang BACKGROUND & AIM: Clostridium difficile-infection (CDI) is a major cause of nosocomial morbidity and mortality in the developed world. Despite significant efforts to control its spread, rates of infection have risen dramatically as antibiotic therapy has become common and widespread. Prevention is mostly focused on measures such as hand-washing and isolation procedures, but as of yet no medication has been identified that is effective at
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on gastrointestinal motility and symptoms in patients with IBS and healthy volunteers (HV). Methods: We recruited patients with IBS based on ROME III criteria. Celiac disease was excluded by a negative IgA TG2 antibody test and duodenal biopsy (Marsh 0-I). HLA-DQ2/ DQ8 status was determined but was not an inclusion criterion. IBS patients were stratified according to their anti-gliadin antibody (AGA) status. A cohort of healthy volunteers (HV) was used as control. Symptoms and gastrointestinal (GI) transit were studied before and after 1-month of GFD. GI transit was evaluated by modified SHAPE study. We assessed gut symptoms (Birmingham, Bristol scale and GSRS), anxiety and depression (HADs), somatic symptoms (PHQ-15) and dietary habits (DQESV2). Fecal microbiota was analysed by 16S rRNA-based Illumina. GFD instructions and compliance were assessed by a trained dietitian. Results : Thirty five IBS patients (15 AGA+ and 20 AGA-) and 26 healthy volunteers were enrolled. Compared to HV, GI transit normalized after GFD in 42% of IBS AGA+ patients vs 25% in IBS AGA- patients. Overall GI symptoms, particularly indigestion (p=0.02), diarrhea (p=0.008) and abdominal pain (p=0.005) improved after GFD in the IBS AGA+ patients but there were no changes in GI symptoms in IBS AGA- patients. Similarly, depression scores decreased in IBS AGA+ but not in IBS AGA- patients. Overall wellbeing, especially positivity (p=0.007) and vitality (p=0.02), improved in IBS AGA+ but not in IBS AGApatients. Individual shifts in microbiota profiles, with overall mild decrease in Firmicutes/ Bacteroidetes ratio was observed in the IBS AGA+ patients. GFD diet had overall no effect in healthy volunteers, although some of them developed constipation. Conclusions: The results suggest that the stratification by anti-gliadin antibody status can identify a subgroup of IBS patients that respond symptomatically to GFD. The gluten-free diet does not seem to improve GI symptoms, overall wellbeing or gut function in IBS patients without AGA.
to be the best treatment as compared to placebo [OR = 6.14, 95% C.I. (2.81 - 13.41)]. RTT was a close second as compared to placebo [OR = 6.08, 95% C.I. (2.01 - 18.37)] (Figure 2). Between pharmacological treatments, TCAs were the best drugs for management as compared to placebo [OR = 4.08 (2.13, 7.84)] and SSRIs were also found to be effective as compared to placebo 2.54 (1.09, 5.94). CBT was also superior to Probiotics [OR = 2.65 (1.08, 6.55)] but not superior to hypnotherapy, MCPT or RTT. Similarly, TCAs were not superior to SSRIs in treatment of IBS. Imprecise estimates and the small number of direct trials lowered our confidence in several comparisons. CONCLUSIONS: In patients with IBS, the best therapy is non-pharmacological, CBT followed by RTT. Between pharmacological therapies, TCAs were better than placebo but not superior to SSRIs.
Mo1654 FODMAPs: Fermentation and Symptom Severity in Functional Gastrointestinal Disorders Juan S. Lasa, Pablo A. Olivera, Guillermo Dima, Angel D. Peralta, Robert Prizont, Luis O. Soifer
Network of included studies .
Background: The use of reduced amounts of food with oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) has shown to be an effective measure to reduce symptom severity in patients with functional gastrointestinal disorders (FGD). However, not all patients could make an association between ingested dietary FODMAP and worsening of their symptoms. Aim: To compared symptom severity and degree of fermentation between patients with FGD in whom FODMAP foods worsened their symptoms, and FGD patients in whom FODMAP foods did not worsen their symptoms. Patients and Methods. A group of 147 patients with FGD (125 women, mean age 50 y) classified according to the Rome III Criteria as Irritable Bowel Syndrome (IBS), CFAB and chronic abdominal pain (AP). Patients were consecutively studied and included 65 IBS/Diarrhea (IBS/D), 39 IBS/Constipation (IBS/C), 14 with mix constipation and diarrhea (IBC/CD), 27 CFAB and 2 AP. Fermentation was evaluated by the breath hydrogen (H2) test. At baseline and after ingestion of 10g lactulose, H2 concentration in expired air was measured for 3 hours with sampling every 20 minutes. A fermentative profile (FP) was developed by calculating the area under the curve of H2 concentration/time. All subjects completed two questionnaires, the first referred to the clinical characteristics of patients and foods that aggravate their symptoms and the second referred to the symptom severity score (SSS), the estimation of the overall symptom severity (OSS), abdominal pain (AP), subjective abdominal bloating (BLO), evacuation disturbance (EVAC) and the degree of symptom interference with daily activities (IDA). A two tail t-test was used for statistical comparison between the two groups; significance was set at p<0.05. Results. Overall, 111 subjects (76 % of the total group) reported worsened symptoms by dietary FODMAPs whereas 36 could not established a link between FODMAPs and digestive symptoms. With the exception of EVAC, all reported scale variables of symptom severity (SSS, OSS, AP) were statistically significantly higher in IBS, CFAB, AP patients who reported worsened symptoms by ingestion of dietary FODMAPS. By contrast, there was no difference in the FP between IBS, CAB, AP patients worsened by FODMAPs and FGD patients in whom symptoms were unaltered by FODMAPs. Conclusions. This case-control-study in FGD patients showed a strong relationship between severity of abdominal symptoms associated to FODMAPs as measured by validated scales and a positive history of symptom aggravation induced by these dietary sugars, oligosaccharides and polyols. The increase in symptom severity was not associated to an increase in expired breath H2 and FP suggesting that an increase in H2 by the colon microbiota may not be responsible for the symptom severity associated with FODMAPs
Pooled Summary Estimates From Indirect Estimates and Network Meta-Analysis Informing on Comparative Efficacy of interventions for IBS symptoms improvement
Mo1656 Outcomes of Fidaxomicin Treatment of Clostridium difficile Infection Clayton M. Spiceland, George Saffouri, Darrell Pardi, Sahil Khanna PURPOSE: Fidaxomicin is a narrow spectrum antibiotic used for the treatment of Clostridium difficile infection (CDI). We evaluated response and recurrence rates of CDI after treatment with fidaxomicin. METHODS: All cases of CDI treated with fidaxomicin at 3 referral centers over a 4 year period were identified using the electronic medical record. Inclusion criteria included a definite CDI diagnosis (3 or more episodes of watery diarrhea in a 24-hour period and positive Clostridium difficile stool assay) and treatment with fidaxomicin 200 mg twice daily for 10 days. Response was defined as resolution of diarrhea. Recurrence was defined if, after symptom resolution, CDI diagnostic criteria were met within 8 weeks of initial diagnosis. Diarrhea recurring after 8 weeks of resolution was considered a new episode. All patients had at least 8 weeks of follow up. Data collected included demographics, number of prior CDI episodes, prior CDI treatment, response to fidaxomicin, recurrence, and adverse effects. RESULTS: 81 patients with median age 56 years; 53% female; 26% with inflammatory bowel disease (IBD) were identified. Most patients (75%) had prior episodes of CDI with a median of 2 previous episodes (range 0 to 8). 90% and 89% were treated with one or more courses of metronidazole and vancomycin respectively; 5 patients had prior fecal transplantation. Complete response occurred in 73 patients (90%) while 8 (10%) had no response; 19% of responders had recurrent CDI. Responders had fewer prior episodes of CDI (median 1, range 0 to 8), compared to non-responders (median 2.5, range 1 to 8), p= 0.01. Responders who did not recur had fewer prior episodes of CDI (median 1, range 06) than patients who recurred (median 2, range 1 to 8), p=0.005. The rate of response in patients with a first episode (n=20) was 100%, compared to 95% in patients with one prior episode (n=22/23) and 82% in patients with 2 or more episodes (n=31/38), p=0.02. Of responders, the rates of recurrent CDI in patients with a first episode was 0%, compared to 23% in patients with one prior episode and 29% in patients with 2 or more episodes, p=0.005. All patients with IBD (n=21) responded to fidaxomicin, with 19% experiencing recurrence. There were no adverse events reported with fidaxomicin. CONCLUSION: In the largest post-clinical trial study of fidaxomicin, we demonstrate that fidaxomicin is effective in treating CDI in clinical practice, including patients with recurrent infection and IBD. All patients treated with fidaxomicin for a first episode of CDI responded with no recurrences. Patients with one or more prior CDI episodes were less likely to respond and more likely to recur suggesting that fidaxomicin use early in CDI course may be more beneficial than later use.
Mo1655 Effectiveness of Pharmacological and Non-Pharmacological Therapies for Irritable Bowel Syndrome: A Systematic Review and Bayesian Network MetaAnalysis Sushil Kumar Garg, Vaibhav Wadhwa, Chimaobi M. Anugwom, Nancy Gupta, John George, Madhusudhan R. Sanaka, Shahnaz Sultan BACKGROUND/AIMS: Few head-to-head trials have been conducted comparing pharmacological with non-pharmacological therapies for Irritable Bowel Syndrome. The objective of this study was to perform a Bayesian network meta-analysis combining direct and indirect treatment comparisons to assess the comparative effectiveness of pharmacological and nonpharmacological treatments for IBS. METHODS: We conducted a systematic literature review in Medline (1946-October 2015), EMBASE (1974-October 2015), and the Cochrane controlled trials registry for randomized controlled trials of adults with IBS. Specifically, we included the trials that compared the efficacy of active interventions [Selective serotonin reuptake inhibitors (SSRIs), Tricyclic Antidepressants (TCAs), cognitive behavioral therapy (CBT), multicomponent psychodynamic therapy (MCPT), relaxation training therapy RTT), hypnotherapy, fiber diet (bran and ispaghula) and probiotics) with each other or placebo on improving IBS symptoms. We performed both direct and Bayesian network meta-analysis for all treatments. The primary outcome of our network meta-analysis was failure in improvement in IBS symptoms (as defined by the individual studies). RESULTS: We included 72 randomized controlled trials consisting of total 5832 patients comparing 10 different interventions (Figure1). In non-pharmacological interventions for IBS, CBT was considered
AGA Abstracts
Mo1657 Lactulose and the Risk of Clostridium difficile-Infection in Decompensated Cirrhosis Anant Agarwalla, Andrew Rhim, Andrew T. Weber, Sonya Davey, David S. Goldberg, YuXiao Yang BACKGROUND & AIM: Clostridium difficile-infection (CDI) is a major cause of nosocomial morbidity and mortality in the developed world. Despite significant efforts to control its spread, rates of infection have risen dramatically as antibiotic therapy has become common and widespread. Prevention is mostly focused on measures such as hand-washing and isolation procedures, but as of yet no medication has been identified that is effective at
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