Richard J. Saad

Do Stool Form and Frequency Correlate With Whole-Gut and Colonic Transit? Results From a Multicenter Study in Constipated Individuals and Healthy Controls

OBJECTIVES:Despite a lack of supportive data, stool form and stool frequency are often used as clinical surrogates for gut transit in constipated patients. The aim of this study was to assess the correlation between stool characteristics (form and frequency) and gut transit in constipated and healthy adults.METHODS:A post hoc analysis was performed on 110 subjects (46 chronic constipation) from nine US sites recording stool form (Bristol Stool Scale) and frequency during simultaneous assessment of whole-gut and colonic transit by wireless motility capsule (WMC) and radio-opaque marker (ROM) tests. Stool form and frequency were correlated with transit times using Spearmans rank correlation. Accuracy of stool form in predicting delayed transit was assessed by receiver operating characteristic analysis.RESULTS:In the constipated adults (42 females, 4 males), moderate correlations were found between stool form and whole-gut transit measured by WMC (r=−0.61, P<0.0001) or ROM (−0.45, P=0.0016), as well as colonic transit measured by WMC (−0.62, P<0.0001). A Bristol stool form value <3 predicted delayed whole-gut transit with a sensitivity of 85% and specificity of 82% and delayed colonic transit with a sensitivity of 82% and specificity of 83%. No correlation between stool form and measured transit was found in healthy adults, regardless of gender. No correlation was found between stool frequency and measured transit in constipated or healthy adults. The correlation between stool frequency and measured transit remained poor in constipated adults with <3 bowel movements per week.CONCLUSIONS:Stool form predicts delayed vs. normal transit in adults. However, only a moderate correlation exists between stool form and measured whole-gut or colonic transit time in constipated adults. In contrast, stool frequency is a poor surrogate for transit, even in those with reduced stool frequency.

Pharmacologic and Complementary and Alternative Medicine Therapies for Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by episodic abdominal pain or discomfort in association with altered bowel habits (diarrhea and/or constipation). Other gastrointestinal symptoms, such as bloating and flatulence, are also common. A variety of factors are believed to play a role in the development of IBS symptoms, including altered bowel motility, visceral hypersensitivity, psychosocial stressors, altered brain-gut interactions, immune activation/low grade inflammation, alterations in the gut microbiome, and genetic factors. In the absence of biomarkers that can distinguish between IBS subgroups on the basis of pathophysiology, treatment of this condition is predicated upon a patients most bothersome symptoms. In clinical trials, effective therapies have only offered a therapeutic gain over placebos of 7-15%. Evidence based therapies for the global symptoms of constipation predominant IBS (IBS-C) include lubiprostone and tegaserod; evidence based therapies for the global symptoms of diarrhea predominant IBS (IBS-D) include the probiotic Bifidobacter infantis, the nonabsorbable antibiotic rifaximin, and alosetron. Additionally, there is persuasive evidence to suggest that selected antispasmodics and antidepressants are of benefit for the treatment of abdominal pain in IBS patients. Finally, several emerging therapies with novel mechanisms of action are in development. Complementary and alternative medicine therapies including probiotics, herbal therapies and acupuncture are gaining popularity among IBS sufferers, although concerns regarding manufacturing standards and the paucity of high quality efficacy and safety data remain.

Heightened Colon Motor Activity Measured by a Wireless Capsule in Patients With Constipation: Relation to Colon Transit and IBS

Relationships of regional colonic motility to transit in health, constipation, and constipation-predominant irritable bowel syndrome (C-IBS) are poorly characterized. This study aimed to 1) characterize regional differences in colon pressure, 2) relate motor differences in constipation to colon transit, and 3) quantify the role of IBS in altered contractility with constipation. Colon pH and pressure were measured by wireless capsules in 53 healthy and 36 constipated subjects. Numbers of contractions >25 mmHg and areas under curves (AUC) were calculated for colon transit quartiles by time. Constipation was classified as normal transit (<59 h), moderate slow transit (STC) (59-100 h), and severe STC (>100 h). Twelve out of 36 constipated subjects had C-IBS; 24 had functional constipation. Numbers of contractions and AUCs increased from the first to the fourth quartile in health (P < 0.0001). Mean numbers of contractions in constipated subjects were similar to controls. Mean AUCs with normal transit (P = 0.01) and moderate STC (P = 0.004) but not severe STC (P = NS) were higher than healthy subjects. IBS was associated with greater mean numbers of contractions (P = 0.05) and AUCs (P = 0.0006) vs. controls independent of transit. Numbers of contractions increased from the first to fourth quartiles in moderate STC, C-IBS, and functional constipation; AUCs increased from the first to fourth quartiles in all groups (all P < 0.05). In conclusion, colon pressure activity is greater distally than proximally in health. Constipated patients with normal or moderately delayed transit show increased motor activity that is partly explained by IBS. These findings emphasize differential effects on transit and motility in different constipation subtypes.

Agents that act luminally to treat diarrhoea and constipation

Diarrhoea and constipation are common clinical complaints that negatively affect quality of life, reduce work productivity and lead to considerable health-care expenditure. A variety of therapies have been used to treat these conditions. Unlike drugs that require systemic absorption to exert their effects, luminally acting agents improve diarrhoea and constipation by altering intestinal and/or colonic motility, as well as mucosal absorption and secretion, through a variety of mechanisms. Examples of luminally acting agents for diarrhoea include peripherally acting opiate analogues, enkephalinase inhibitors, bile-acid binding agents, nonabsorbed antibiotics, probiotics, bismuth-containing compounds, berberine and agents with possible effects on intestinal secretion or permeability. Luminally acting drugs for constipation include bulking agents, surfactants, osmotics, stimulants, chloride-channel activators, probiotics, drugs that increase delivery of bile acids to the colon and natural therapies such as prunes and hemp seed extract. As the physiological effects of luminally acting drugs are largely confined to the gastrointestinal tract, these agents are unlikely to cause adverse effects outside of the gastrointestinal tract.

M1706 Discontinuation of Lubiprostone Treatment for Irritable Bowel Syndrome with Constipation Is Not Associated with Symptom Increase or Recurrence: Results from a Randomized Withdrawal Study

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder with an estimated prevalence of 10–15% in Western countries. • Diagnosis of IBS is based upon the presence of abdominal discomfort/pain with changes in bowel habits. In clinical practice and research, IBS patients are • subgrouped on the basis of differences in bowel habits. Approximately 1/3 of IBS patients suffer with IBS and constipation (IBS-C). Current therapies for IBS-C tend to target relieving individual symptoms of constipation, abdominal pain or bloating rather than the totality of IBS symptoms. • Lubiprostone, a selective activator of type-2 chloride channels (CIC-2), is approved for the treatment of chronic idiopathic constipation in adults and for the • treatment of IBS-C in adult women. Lubiprostone enhances fluid secretion into the intestinal lumen without altering serum electrolyte levels. • Patients with IBS may exhibit abnormal gut permeability and an associated intestinal inflammatory response. Lubiprostone stimulates recovery of mucosal • barrier function in animal models suggesting a possible mechanism for the clinical improvement observed in patients on this drug.* Given the intermittent nature of IBS-C symptoms, short-term interventions for symptomatic relief of IBS-C may be appropriate in some patients. Such • interventions need to be efficacious and not associated with rebound effects following discontinuation of treatment.

How Do US Gastroenterologists Use Over-the-Counter and Prescription Medications in Patients With Gastroesophageal Reflux and Chronic Constipation?

Background:The aim of this study was to assess how US gastroenterologists perceive and utilize over-the-counter (OTC) and prescription medications for gastroesophageal reflux disease (GERD) and chronic constipation (CC).Methods:A total of 3,600 randomly selected American Gastroenterological Association (AGA) members were mailed a 27-question survey that assessed their perceptions and use of OTC and prescription medications. The χ2 test and Student’s t-test were utilized for bivariate analysis.Results:A total of 830 gastroenterologists (23.1%) completed the survey. For the typical acid reflux patient, 50% of gastroenterologists recommended OTC proton pump inhibitors (PPIs), 13% recommended an OTC histamine2 receptor antagonist, whereas 33% recommended a prescription PPI. However, in the typical CC patient, 97% of gastroenterologists initially utilized OTC treatments. The vast majority of gastroenterologists felt that OTC brand name and store brand PPIs (76%) and polyethylene glycol (PEG 3350; 90%) were equally effective. Despite this, a minority “always” or “very often” directed their patients to purchase a store brand PPI (35%) or laxative (40%). In addition, gastroenterologists tended to underestimate the cost savings associated with store brand medicines and had limited knowledge regarding the regulation of store brands.Conclusions:Among US gastroenterologists, OTC medications now dominate primary therapy of GERD and CC. Despite feeling that name brand and store brand PPIs and laxatives are equally effective, the majority of gastroenterologists recommend brand name medicines and underestimate the cost savings associated with store brands. In this age of accountable care, greater efforts to help physicians and patients to better utilize their health-care dollars is warranted.

M1806 Complaints Suggestive of Irritable Bowel Syndrome Are Common in Patients with Puborectalis Dyssynergia: An Under-Recognized Overlap Syndrome

causes of constipation, whereas physicians in the UK and Germany also considered sedentary lifestyle to be an important factor. GEs and GPs from all countries defined normal stool frequency to range from 2-3 BMs daily to one BM every 2nd/3rd day, consistent with criteria proposed by Connell (BMJ 2: 1095, 1965). Awareness of Rome Criteria was 98%, 62% & 54% among GEs from US, UK & Germany, but was lower among GPs (54%, 12% & 23% in US, UK & Germany, respectively). Regardless of awareness, few physicians (GEs: 1529%, GPs: 4-9%) reported using the Rome criteria for diagnostic purposes. In all countries, almost all physicians indicated recommending lifestyle change as part of their initial approach for treating constipation. Recommendation of laxatives however, differed among countries. In the US, the majority of GEs (94-100%) and GPs (68-100%) reported recommending laxatives as initial treatment for all levels of constipation severity (mild severe). In contrast, only 12 and 8% of GEs and 25 and 4% of GPs in the UK and Germany, respectively, reported recommending laxatives initially for mild constipation, but increased their use with increasing severity and in follow-up consultation. Conclusions: There is need to educate both GEs and GPs in the US, UK, and Germany about symptoms, causes, diagnostic criteria, and treatment of constipation.

950 Assessment of Colonic, Whole Gut and Regional Transit in Elderly Constipated and Healthy Subjects with a Novel Wireless pH/Pressure Capsule (SmartPill®)

Introduction:Upper gastrointestinal function may change over time in healthy or impaired motility patient groups. Identifying any physiological changes of the GI tract as it ages would be important in order to classify true GI malfunction in older populations. The SmartPill capsule (SP) can do this by measuring the gastric emptying time (GET) and record the GI intraluminal pressures non-invasively. Aim:To determine if gastric function changes over time in healthy subjects and patients with gastroparesis (GP). Methods:Healthy (GET>5h) and GP (GET 3units above gastric pH. Healthy and GP subjects were each divided into age groups: age>65 and age 65y.o. was significantly slower than subjects 0.3) or after GET (p>0.4). In the comparison of subgroups, there was no significant difference in GET between quartiles (p>0.1) except Q1 had a significantly faster GET than Q4. In the 42 GP subjects, there was no significant difference in GET between subjects >65y.o. and 0.06) or after GET (p>0.1). Conclusion:The GET of subjects over the age of 65 is slower than subjects between the ages of 19-34 in the healthy population. There appears to be no difference in GET among the other age groups, as well as no difference in GI contractility. The increase of delayed GET with age should be taken into consideration in drug development that may use younger populations to assess drug efficacy. The normal range of delayed gastric emptying in patients over the age of 65 may have to be extended as it may increase with age.

Abdominal Symptoms Are Common and Benefit from Biofeedback Therapy in Patients with Dyssynergic Defecation

Objectives:Dyssynergic defecation (DD) is a subtype of chronic constipation that responds to biofeedback therapy (BFT). Abdominal, anorectal, and stool symptoms are commonly reported by DD patients, but limited data exist to demonstrate the improvement of these associated symptoms to BFT. Aims to prospectively study the response of constipation and associated abdominal, rectal, and stool symptoms to biofeedback in a population with dyssynergia.Methods:Patients with DD as determined by anorectal manometry and balloon expulsion testing were included into the study. All patients completed a validated survey, the Personal Assessment of Constipation Symptom (PAC-SYM) questionnaire, before and following BFT. The PAC-SYM is a clinical tool to assess constipation-related symptom frequency and severity.Results:Seventy-seven dyssynergic patients fulfilled the study requirements. Abdominal symptoms were present in up to 74% of patients with dyssynergia. PAC-SYM summation scores improved following completion of biofeedback by 48%, from 22.08 to 11.48 (P<0.001). The proportion of patients with at least moderate symptoms decreased in all 12 questionnaire items, including all abdominal symptoms, after completing BFT (46.8% to 14.3%, P<0.001).Conclusions:Abdominal symptoms are common in patients with dyssynergia. BFT improves both anorectal-related constipation symptoms and associated abdominal symptoms in patients with DD. Limitations of this study are observational design, lack of control group, and lack of long-term follow-up.

S1333 A Comparison of Two Radio-Opaque Marker Methodologies in the Assessment of Colonic Transit of Adults With Constipation

of 4.The IBS-M showed the highest likelihood ratio for changing while the IBS-U showed the lowest ratio. Conclusions:Patients with IBS have less than a 38% probability of having a Bristol between 3 and 5 except for the IBS-U that has a 78% probability. A 4-week treatment with PB+S has a notable impact on the expected frequency of stool patterns, especially in the IBS-M followed by the IBS-C. Figure show the basal and after treatment expected frequencies of stool patterns in IBS-C.