Irritable Bowel Syndrome With Diarrhea Research Articles

Su1377 Efficacy of Oral Ibodutant in IBS-D Female Patients Measured by Abdominal Pain Severity - An Iris 2 Post-Hoc Analysis

Introduction Ibodutant, a selective and potent antagonist of neurokinin 2 receptors under clinical development for Irritable Bowel Syndrome with Diarrhea (IBS-D). A phase II (IRIS 2) study tested the efficacy of 8-week oral treatment with 3 doses of ibotudant in a total 559 IBS-D patients defined by Rome III criteria. Based on the combined response of satisfactory relief of IBS symptoms and abdominal pain/discomfort according to the 75% rule, i.e. positive response in at least 6 out of 8 treatment weeks (primary end-point), a statistically and clinically relevant efficacy was demonstrated in the female subgroup (n=333) at the 10 mg dose with 46.84% of responders vs 24.36% in placebo (p=0.0034). Aim To evaluate the benefit of ibodutant in the female population exposed to the efficacious oral daily dose of 10 mg participating to the IRIS 2 study when considering the mean abdominal pain severity score at baseline. Methods The analysis of primary efficacy end-point was repeated classifying female patients according to the mean abdominal pain score at baseline, as recorded on the daily diary during the 2 week no-treatment run-in phase, with pain rating on a 0-4 scale (0= no pain; 4= very severe). Two severity categories were considered, with mean score > 2 defining patients with severe/very severe pain. Results At baseline, n= 228 female patients (40.79% of total patients) reported severe/very severe mean abdominal pain score. In this population, ibodutant 10 mg confirmed the high clinically and statistically significant superiority to placebo in terms of reaching satisfactory relief of overall IBS symptoms and abdominal pain/discomfort, with a response rate of 47.06% versus 21.05% (p=0.0044). The same magnitude of responders (46.43%) was shown in patients reporting mild /moderate abdominal pain score at baseline, however responders to placebo was consistently higher (33.3%), and the difference did not reach statistical significance. Conclusion When the severity criteria of IBS-D patients are established according to the abdominal pain at baseline, ibodutant confirmed a significant benefit at 10 mg once daily dose in the severe/very severe female population. The analysis also showed patients with lower pain intensity are characterized by a significantly higher placebo response.

Su1379 Using the FDA Composite Endpoint for IBS-D to Compare Treatment Effectiveness of Existing and Investigational Therapeutic Options

Introduction Ibodutant, a selective and potent antagonist of neurokinin 2 receptors under clinical development for Irritable Bowel Syndrome with Diarrhea (IBS-D). A phase II (IRIS 2) study tested the efficacy of 8-week oral treatment with 3 doses of ibotudant in a total 559 IBS-D patients defined by Rome III criteria. Based on the combined response of satisfactory relief of IBS symptoms and abdominal pain/discomfort according to the 75% rule, i.e. positive response in at least 6 out of 8 treatment weeks (primary end-point), a statistically and clinically relevant efficacy was demonstrated in the female subgroup (n=333) at the 10 mg dose with 46.84% of responders vs 24.36% in placebo (p=0.0034). Aim To evaluate the benefit of ibodutant in the female population exposed to the efficacious oral daily dose of 10 mg participating to the IRIS 2 study when considering the mean abdominal pain severity score at baseline. Methods The analysis of primary efficacy end-point was repeated classifying female patients according to the mean abdominal pain score at baseline, as recorded on the daily diary during the 2 week no-treatment run-in phase, with pain rating on a 0-4 scale (0= no pain; 4= very severe). Two severity categories were considered, with mean score > 2 defining patients with severe/very severe pain. Results At baseline, n= 228 female patients (40.79% of total patients) reported severe/very severe mean abdominal pain score. In this population, ibodutant 10 mg confirmed the high clinically and statistically significant superiority to placebo in terms of reaching satisfactory relief of overall IBS symptoms and abdominal pain/discomfort, with a response rate of 47.06% versus 21.05% (p=0.0044). The same magnitude of responders (46.43%) was shown in patients reporting mild /moderate abdominal pain score at baseline, however responders to placebo was consistently higher (33.3%), and the difference did not reach statistical significance. Conclusion When the severity criteria of IBS-D patients are established according to the abdominal pain at baseline, ibodutant confirmed a significant benefit at 10 mg once daily dose in the severe/very severe female population. The analysis also showed patients with lower pain intensity are characterized by a significantly higher placebo response.

New therapeutic option for irritable bowel syndrome: serum-derived bovine immunoglobulin.

Oral prescription medical foods have long been used in hospital settings but are also appropriate therapies for gastrointestinal disorders in outpatient medical practice. Oral serum-derived bovine immunoglobulin/protein isolate (SBI) has been shown in clinical studies to reduce loose stools and improve stool consistency as well as other symptoms (i.e., abdominal pain, bloating, and urgency) in patients with irritable bowel syndrome with diarrhea (IBS-D) and human immunodeficiency virus-associated enteropathy. This case series reports the outcomes of 14 IBS patients who received SBI as an addition to standard of care at an individual physician's clinical practice. The patients: 2 IBS with constipation (IBS-C), 7 IBS-D, 2 mixed diarrhea and constipation IBS (IBS-M) and 3 undefined IBS (IBS-U; also described by some physicians as IBS-Bloating), ranged in age from 22-87 years. SBI (5 g or 10 g daily dose) was added to the patient's current standard care and followed for several weeks to determine if symptoms were improved with the addition of SBI. Overall, 12 of the 14 patients indicated some level of improvement through direct questioning of the patients regarding changes from the prior visit. One IBS-Bloating patient had a resolution of symptoms and two patients (1 IBS-Bloating and 1 IBS-C) discontinued therapy because of insufficient relief. The 12 patients who continued on therapy reported an overall improvement in symptoms with better stool consistency, decreased frequency as well as reductions in abdominal pain, bloating, distention, and incontinence. In most cases, therapeutic effects of SBI were seen within the first four weeks of therapy with continued improvements at subsequent visits. SBI has a multifaceted mechanism of action and may help to manage IBS by providing a distinct protein source required to normalize bowel function, gastrointestinal microbiota, and nutritionally enhance tight junction protein expression between intestinal epithelial cells. SBI as a medical food provides a safe option for patients with IBS-D but may have application in other forms of IBS.

A mechanistic multicentre, parallel group, randomised placebo-controlled trial of mesalazine for the treatment of IBS with diarrhoea (IBS-D)

IntroductionImmune activation has been reported in the mucosa of IBS patients with diarrhoea (IBS-D), and some small studies have suggested that mesalazine may reduce symptoms. We performed a double-blind, randomised...

The clinical potential of ramosetron in the treatment of irritable bowel syndrome with diarrhea (IBS-D).

Irritable bowel syndrome (IBS) is a highly prevalent functional bowel disorder. Serotonin (5-HT) is known to play a physiological and pathophysiological role in the regulation of gastrointestinal function. In experimental studies, 5-HT3 receptor antagonists have been reported to slow colon transit, to blunt gastrocolonic reflex, and to reduce rectal sensitivity. Alosetron and cilansetron, potent and selective 5-HT3 receptor antagonists, have proven efficacy in the treatment of IBS with diarrhea (IBS-D). However, alosetron was voluntarily withdrawn due to postmarketing reports of ischemic colitis and complications of constipation, and cilansetron was never marketed. Currently alosetron is available under a risk management program for women with severe IBS-D. Ramosetron is another potent and selective 5-HT3 receptor antagonist, which has been marketed in Japan, South Korea, and Taiwan. In animal studies, ramosetron reduced defecation induced by corticotrophin-releasing hormone and had inhibitory effects on colonic nociception. In two randomized controlled studies including 957 patients with IBS-D, ramosetron increased monthly responder rates of patient-reported global assessment of IBS symptom relief compared with placebo. Ramosetron was also as effective as mebeverine in male patients with IBS-D. In a recent randomized controlled trial with 343 male patients with IBS-D, ramosetron has proved effective in improving stool consistency, relieving abdominal pain/discomfort, and improving health-related quality of life. Regarding safety, ramosetron is associated with a lower incidence of constipation compared with other 5-HT3 receptor antagonists and has not been associated with ischemic colitis. Although further large prospective studies are needed to assess whether ramosetron is effective for female patients with IBS-D and to evaluate its long-term safety, ramosetron appears to be one of the most promising agents for patients with IBS-D.

An exploration of the barriers to the confident diagnosis of irritable bowel syndrome: A survey among general practitioners, gastroenterologists and experts in five European countries.

The diagnostic processes for chronic abdominal conditions are challenging. Despite their tendency for diagnostic tests in patients with irritable bowel syndrome (IBS) symptoms, clinicians are encouraged to make a positive diagnosis based on symptom criteria without alarm signs. We explored how European physicians diagnose and manage patients suffering from IBS. We conducted a vignette-based survey to evaluate the diagnostic approaches in four standardized patients with IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), inflammatory bowel disease (IBD) and chronic constipation (CC). General practitioners (GP, n = 104), gastroenterologists (GE, n = 100) and IBS experts (n = 25) from five European countries participated. Experts showed the highest rates of correct diagnoses (88%-92%) for all cases except CC (only 60%) and were more prone to a positive diagnosis (64%/68% in IBS-C/CC), whereas GEs and GPs tended toward a diagnosis by exclusion (63%/63% and 62%/60% in IBS-C/CC). In the CC vignette, conducting tests was more frequent than prescribing treatment among 44% experts, 63% GEs and 36% GPs. The diagnosis of IBD presented little difficulty for any of the participants. This study highlights the difficulties in confidently diagnosing chronic functional bowel conditions, especially for non-experts, whereas IBD caused little difficulty. Differentiating between IBS-C and CC seemed particularly challenging, even for experts.

Evaluation of Alosetron Using the New FDA Composite Endpoint Demonstrates Strong Treatment Effect in Females With Severe Irritable Bowel Syndrome With Diarrhea

Introduction: Prior to 2010, most clinical trials of drug treatments for irritable bowel syndrome (IBS) evaluated drug effect by a global measure of overall IBS condition (i.e., adequate relief) and grading of specific relevant symptoms (i.e., abdominal pain, bowel urgency, stool form). The new FDA recommended assessment uses composite or co-primary endpoints which quantify the sum of scores for abdominal pain (AP) and stool consistency (SC) for IBS with diarrhea (IBS-D). To determine if previously approved drugs are also effective by the new FDA standard, we evaluated data from two pivotal Phase III alosetron (ALO) trials [S3BA3001 and 3002 selecting only severe IBS-D patients (mean SC ≥3.5; mean AP ≥2.0; bowel urgency on ≥50% days and, if available, IBS-impaired activity on ≥25% days)] plus one post marketing (PM) double blind placebo controlled study (S3B30040) conducted in female patients who met appropriate Rome IBS criteria. The PM study entered only female patients with severe IBS-D. Methods: In all 3 trials, patients met baseline criteria for eligibility and were randomized to 12 weeks treatment with ALO 1.0 mg bid or placebo (PBO). Symptoms were self assessed daily and registered using a telephone reporting system to rate AP [1=none; 5=severe] and SC [1=very hard; 5=watery]. Data from the 3 trials were mined to select for analysis only patients having baseline criteria for severe IBS-D. A monthly responder showed advantage for ALO over PBO in the composite endpoint for ≥2 of 4 weeks. Comparison of responder results is based on Fisher’s exact test. Results: The table shows differences in responder rates (ALO minus PBO) for the new composite endpoint in both treatment groups in the 3 studies (**p≤0.005; *p≤0.05). Conclusion: Re-analysis of similar, high quality alosetron clinical trials using the FDA recommended composite endpoint demonstrated a robust positive treatment effect for alosetron, as was also shown (p≤0.05) in the same patients for the adequate relief endpoint. Both endpoints gave similar results and support a significant treatment effect with alosetron. Results are among the first to compare treatment effect between the older global and newer composite score endpoints. Disclosure - Dr. Camilleri - no relevant disclosures. Dr. Krause - no relevant disclosures. Dr. Deveze - Employee of Prometheus Laboratories Inc. Dr. Rao - Employee of Prometheus Laboratories Inc. Dr. Earnest - Consultant for Prometheus Laboratories Inc. This research was supported by an industry grant from The study was conducted by financial support from Prometheus Laboratories Inc.Table 1

MicroRNA 29 Targets Nuclear Factor-κB–Repressing Factor and Claudin 1 to Increase Intestinal Permeability

Some patients with irritable bowel syndrome with diarrhea (IBS-D) have intestinal hyperpermeability, which contributes to their diarrhea and abdominal pain. MicroRNA 29 (MIR29) regulates intestinal permeability in patients with IBS-D. We investigated and searched for targets of MIR29 and investigated the effects of disrupting Mir29 in mice. We investigated expression MIR29A and B in intestinal biopsies collected during endoscopy from patients with IBS (n = 183) and without IBS (controls) (n = 36). Levels were correlated with disease phenotype. We also generated and studied Mir29(-/-) mice, in which expression of Mir29a and b, but not c, is lost. Colitis was induced by administration of 2,4,6-trinitrobenzenesulfonic acid; intestinal tissues were collected and permeability was assessed. Microarray analysis was performed using tissues from Mir29(-/-) mice. Changes in levels of target genes were measured in human colonic epithelial cells and small intestinal epithelial cells after knockdown of MIR29 with anti-MIRs. Intestinal tissues from patients with IBS-D (but not IBS with constipation or controls) had increased levels of MIR29A and B, but reduced levels of Claudin-1 (CLDN1) and nuclear factor-κB-repressing factor (NKRF). Induction of colitis and water avoidance stress increased levels of Mir29a and Mir29b and intestinal permeability in wild-type mice; these increased intestinal permeability in colons of far fewer Mir29(-/-) mice. In microarray and knockdown experiments, MIR29A and B were found to reduce levels of NKRF and CLDN1 messenger RNA, and alter levels of other messenger RNAs that regulate intestinal permeability. Based on experiments in knockout mice and analyses of intestinal tissue samples from patients with IBS-D, MIR29 targets and reduces expression of CLDN1 and NKRF to increase intestinal permeability. Strategies to block MIR29 might be developed to restore intestinal permeability in patients with IBS-D.

American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation.

Irritable bowel syndrome (IBS) and chronic idiopathic constipation ((CIC) also referred to as functional constipation) are two of the most common functional gastrointestinal disorders worldwide. IBS is a global problem, with anywhere from 5 to 15 % of the general population experiencing symptoms that would satisfy a defi nition of IBS ( 1,2 ). In a systematic review on the global prevalence of IBS, Lovell and Ford ( 1 ) documented a pooled prevalence of 11 % with all regions of the world suff ering from this disorder at similar rates. Given its prevalence, the frequency of symptoms, and their associated debility for many patients and the fact that IBS typically occurs in younger adulthood, an important period for furthering education, embarking on careers, and / or raising families, the socioeconomic impact of IBS is considerable. Th ese indirect medical costs are frequently compounded by the direct medical costs related to additional medical tests and the use of various medical and nonmedical remedies that may have limited impact. CIC is equally common; in another systematic review, Suares and Ford ( 3 ) reported a pooled prevalence of 14 % , and also noted that constipation was more common in females, in older subjects, and those of lower socioeconomic status ( 3 ). Chronic constipation has also been linked to impaired quality of life ( 4 ), most notably among the elderly ( 5 ). Neither IBS nor CIC are associated with abnormal radiologic or endoscopic abnormalities, nor are they associated with a reliable biomarker; diagnosis currently rests entirely, therefore, on clinical grounds. Although a number of clinical defi nitions of both IBS and CIC have been proposed, the criteria developed through the Rome process, currently in its third iteration, have been those most widely employed in clinical trials and, therefore, most relevant to any review of the literature on the management of these disorders. According to Rome III, IBS is defi ned on the basis of the presence of:

Intestinal Secretory Mechanisms in Irritable Bowel Syndrome–Diarrhea

Although diarrhea is the predominant bowel dysfunction in as many as one-third of patients with irritable bowel syndrome (IBS), it is unclear whether there is a specific disorder of intestinal fluid or electrolyte secretion in IBS. Diarrhea is generally considered a result of accelerated colonic transit in patients with IBS. Although a primary secretory diathesis has not been well-documented in patients with IBS with diarrhea (IBS-D), several mechanisms that could potentially contribute to intestinal secretion have been reported. Some of these mechanisms also influence motor and secretory dysfunctions that contribute to the pathophysiology of IBS-D. We review the evidence supporting secretion in IBS-D caused by peptides and amines produced by enteroendocrine cells or submucosal neurons, enterocyte secretory processes, and intraluminal factors (bile acids and short-chain fatty acids). Understanding these mechanisms and developing clinical methods for their identification could improve management of patients with IBS-D.

Traditional Chinese medicine (Shun-Qi-Tong-Xie Granule) for irritable bowel syndrome: study protocol for a randomised controlled trial.

BackgroundIrritable bowel syndrome (IBS) is a common gastrointestinal functional disorder with no effective therapy. Traditional Chinese medicine (TCM) is one of the most common complementary therapies in China. We designed this study to evaluate the efficacy and safety of Shun-Qi-Tong-Xie Granule (SQTX Granule), a TCM treatment, in patients with IBS with diarrhea (IBS-D).Methods/DesignA randomised, double-blinded, placebo-controlled, multi-centre, superiority clinical trial to evaluate the efficacy and safety of SQTX Granule is proposed. Eligible patients (Rome III) with IBD-S will be randomly assigned into SQTX Granule group and the placebo group. Patients will receive a 28-day treatment and a 2-month follow-up. The primary outcome measures include the scores of IBS-quality of life (IBS-QOL) rating scale and IBS-symptom severity scale (IBS-SSS) rating scale. The secondary outcome measures include the improvement of symptom scores, and the duration of abdominal pain and diarrhea.DiscussionAccording to TCM theory, SQTX Granule has a regulating effect on abdominal pain, diarrhea and the syndrome of liver-spleen disharmony, which is similar to the symptoms of IBS-D. This study will provide objective evidence to evaluate the efficiency and safety of SQTX Granule in IBS-D treatment.Trial registrationChiCTR-TRC-14004241.Date of registration: 9 February 2014.

PWE-180 A Survey Evaluating General Practitioners’, Gastroenterologists’ And Experts’ Diagnostic Approaches To Inflammatory Bowel Disease, Irritable Bowel Syndrome And Chronic Constipation In Five European Countries

IntroductionThe confident diagnosis of chronic abdominal conditions can be challenging. This study assessed the diagnostic process in irritable bowel syndrome with constipation (IBS‑C), irritable bowel syndrome with diarrhoea (IBS‑D), inflammatory...

Mo1972 Role of SeHCAT Scanning in Diagnosis of Bile Salt Malabsorption: a University Hospital Experience

Introduction: Chronic diarrhoea is a very common presentation in the gastroenterology clinics. Majority of patients with negative investigations for organic disease are often labelled with a diagnosis of irritable bowel syndrome with diarrhoea (IBS-D). Bile salt malabsorption (BMA) is not an uncommon cause of chronic diarrhoea. In clinical practice mostly an empirical trail of bile acid sequestrants is used to diagnose this condition which lacks diagnostic accuracy. 23-seleno-25-homo-tauro-cholic acid (SeHCAT) scan is a reliable, simple and non invasive investigation to detect and treat this condition but has been underutilized in most centres in the United Kingdom (UK). Aims & Methods: We aimed to evaluate the usefulness of SeHCAT scan in evaluating patients with chronic diarrhoea. We retrospectively reviewed all patients who had SeHCAT scan over a two year period in a University Hospital. The integrated hospital electronic database system was reviewed and analysed for the following: clinical details, radiology, biochemistry, endoscopy and histology. BMA was defines as SeHCAT retention of less than 15% (mild 10-15%; moderate 5-10% and severe <5%). Results: 118 patients referred to gastroenterology clinic for chronic diarrhoea underwent SeHCAT testing over the review period. 42 M; 76 F, mean age 51 y (range 16-89). SeHCAT test was positive for BMA in 51/118(43%) of patients. Among positive SeHCAT tests, 27 (53%) had severe, 15 (29%) had moderate and, 9 (17%) had mild BAM. 12 (23%) had type 1 (6 terminal ileal resection and 6 Crohn's Disease), 28 (55%) had type 2 (Idiopathic) and 11 (21.5%) had type 3 (7 cholecystectomy, 2 diabetes, 2 coeliac) BAM. Out of 51 with confirmed BMA on SeHCAT testing, treatment information in the notes was available for 35(68%) of the patients. These patients were treated with bile acid sequestrants, either with colesevalam (n=7) or with cholestyramine (n=28). Colesevalam was well tolerated with 100% good response. In cholestyramine group 12(43%) had good response, 4(7%) partial and 7(25%) showed poor response. All patients with poor response discontinued treatment and 4 (57%) of this group stopped cholestyramine early due to unpleasant side effects. No treatment response was documented in the notes for 5 patients. Overall, colesevalam had excellent response rates with no reported side effects. Conclusion: SeHCAT scan is probably an underutilized test for diagnosing bile salt malabsorption. In patients presenting with chronic diarrhoea SeHCAT scanning must be considered to diagnose this probably under recognised cause of chronic diarrhoea. Colesevalam has better tolerability and response rates and must be considered in group of patients intolerant to cholestyramine.

Inhibitory effect of the selective serotonin 5-HT3 receptor antagonist ramosetron on duodenal acidification-induced gastric hypersensitivity in rats

Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are both functional gastrointestinal disorders and frequently co-occur in patients. While one cause of FD appears to be gastric hypersensitivity, whether the hypersensitivity is affected by IBS treatments remains unclear, given the lack of appropriate animal models for testing. Here, we established an experimental model of duodenal acidification-induced gastric hypersensitivity in conscious rats. The model involved duodenal acidification induced by the infusion of hydrochloric acid into the proximal duodenum, with the nociceptive response being determined as the change in mean arterial pressure (MAP) during gastric distension via an indwelling latex balloon. Using our model we evaluated the effects of duodenal acidification, increased distension pressure, and orally administered therapeutic agents for IBS with diarrhea (IBS-D). Duodenal acidification enhanced the pressor response during gastric distension, and pretreatment with the opioid κ-receptor agonist fedotozine (10mg/kg, intra-arterial) inhibited the pressor response. Pressure levels of 15–60mmHg increased MAP in response to gastric distension. The serotonin 5-HT3 receptor antagonist ramosetron (30μg/kg) inhibited MAP increase induced by duodenal acidification, with no other IBS-D therapeutic agents showing any effect. In contrast, the serotonin 5-HT3 receptor agonist m-chlorophenylbiguanide (1mg/kg) significantly enhanced the pressor response during gastric distension. These findings indicate that the serotonin 5-HT3 receptor plays a key role in duodenal acidification-induced gastric hypersensitivity in rats, suggesting that ramosetron may reduce FD symptoms by ameliorating sensitized gastric perception.

Correlation between DQB1 genetic polymorphism and genetic susceptibility in patients diagnosed with irritable bowel syndrome with diarrhea.

We examined patients of Han nationality diagnosed with irritable bowel syndrome with diarrhea (IBS-D) in Guangdong, China, to analyze the correlation between DQB1 allele polymorphisms and the genetic susceptibility to IBS-D. A total of 120 IBS-D patients of Han nationality in Guangdong, China, and 60 healthy control volunteers were included. DQB1 allele polymorphisms were investigated by polymerase chain reaction. Subjects' serum interleukin (IL)-10 level, colonic permeability, and tight junction marker zonula occludens 1 (ZO1) mRNA level were also investigated. Our data showed that the DQB1*02 allele frequency was significantly higher in IBS-D patients, while the DQB1*0603 frequency was lower than in healthy volunteers. The DQB1*03, DQB1*04, DQB1*05, DQB1*0601, DQB1*0602, and DQB1*0604 alleles did not show significant differences between IBS-D patients and healthy controls. Furthermore, patients with DQB1*03- positive and DQB1*0603-negative alleles showed more severe colonic permeability and lower serum IL-10 level and ZO1 level compared to healthy controls or even IBS-D patients with other genotypes. The present study indicated the DQB1*02 or DQB1*0603 alleles are related to IBS-D occurrence in Guangdong, China, and the mechanism of the disease may be related to reduced serum IL-10 levels.

Case Series of 10 Drug-Refractory IBS Patients Who Respond to Oral Serum-Derived Bovine Immunoglobulin/Protein Isolate (SBI)

Aim: The responses of 10 patients with long-standing, symptomatic, intractable drug-refractory histories of irritable bowel syndrome with diarrhea (IBS-D) and with abdominal pain, gas/bloating and distention, termed IBS undefined (IBS-U), were evaluated when administering a medical food product containing serum-derived bovine immunoglobulin/protein isolate (SBI). Methods: Patients in this case series were chosen based on their lack of satisfactory response to a variety of drugs, including antidiarrheal and antispasmodic medications, serotonin 5-HT3 receptor antagonists, selective serotonin re-uptake inhibitors (SSRIs), proton pump inhibitors (PPIs), antibiotics, and antidepressive drugs. Patients met Rome III criteria and were administered 5 g/day of SBI as standard-of-care nutritional support. A scale of 0% - 25%, 25% - 50%, 50% - 75%, 75% - 100% response to SBI was used for patient-reported improvement in overall IBS symptoms following administration for one month. Exact methods for calculating confidence intervals and p-values were used to assess complete management of symptoms and response to therapy. Adverse events were also monitored for this nutritional product. Results: The onset of gastrointestinal (GI) symptom reduction utilizing nutritional management with SBI occurred within an average time of 2-4 weeks with improved or near complete management in all 10 patients who were refractory to previous drug therapies by 4 weeks. When prompted, patients reported significant IBS symptom improvement which averaged between 50% - 100% (p = 0.002) with an average for complete management in all patients of 69%. No side effects were reported after SBI administration even when taken for up to 28 weeks. Conclusion: Based on the safety profile and reported outcomes in this case report, SBI should be considered as a nutritional option for management in IBS-D and IBS-U.

Irritable bowel syndrome: pathogenesis, diagnosis, treatment, and evidence-based medicine.

Irritable bowel syndrome (IBS) is a chronic and debilitating functional gastrointestinal disorder that affects 9%-23% of the population across the world. The percentage of patients seeking health care related to IBS approaches 12% in primary care practices and is by far the largest subgroup seen in gastroenterology clinics. It has been well documented that these patients exhibit a poorer quality of life and utilize the health care system to a greater degree than patients without this diagnosis. The pathophysiology of IBS is not clear. Many theories have been put forward, but the exact cause of IBS is still uncertain. According to the updated ROME III criteria, IBS is a clinical diagnosis and presents as one of the three predominant subtypes: (1) IBS with constipation (IBS-C); (2) IBS with diarrhea (IBS-D); and (3) mixed IBS (IBS-M); former ROME definitions refer to IBS-M as alternating IBS (IBS-A). Across the IBS subtypes, the presentation of symptoms may vary among patients and change over time. Patients report the most distressing symptoms to be abdominal pain, straining, myalgias, urgency, bloating and feelings of serious illness. The complexity and diversity of IBS presentation makes treatment difficult. Although there are reviews and guidelines for treating IBS, they focus on the efficacy of medications for IBS symptoms using high-priority endpoints, leaving those of lower priority largely unreported. Therefore, the aim of this review is to provide a comprehensive evidence-based review of the diagnosis, pathogenesis and treatment to guide clinicians diagnosing and treating their patients.

Application of empowerment theory on patients with irritable bowel syndrome with diarrhea

Objective To explore the clinical effect of application of empowerment theory on patients with irritable bowel syndrome with diarrhea (IBS-D).Methods Sixty-four patients with IBS-D were chosen and randomly divided into two groups,each with 32 cases.The control group received routine nursing care,and the experimental group received empowerment theory for nursing intervention on the basis of routine nursing care.The curative effect and treating compliance in the two groups were compared,and the quality of life before and after intervention was assessed by IBS-QOL.Results The curative effect was 84.3％ in the experimental group after intervention,and 59.5％ in the control group,and the difference was statistically significant (x2 =4.95,P ＜ 0.05).The score of treating compliance was (36.12 ± 5.84) in the experimental group after intervention,and (29.51 ± 5.36) in the control group,and the difference was statistically significant (t =4.717,P ＜ 0.01).The scores of IBS-QOL in all factors between two groups were no statistically significant before intervention (P ＞0.05).The scores of IBS-QOL in all factors excluding picky eaters dimension in the experimental group after intervention were higher than those of the control group,and the differences were statistically significant (P ＜0.05).Conclusions Empowerment theory helps to improve the patients' quality of life and treating compliance,and enhance the curative effects. Key words: Diarrhea; Irritable bowel syndrome ; Quality of life ; Empowerment theory

Changes in the symptom pattern and the densities of large-intestinal endocrine cells following Campylobacter infection in irritable bowel syndrome: a case report

BackgroundIrritable bowel syndrome (IBS) is a common chronic functional gastrointestinal disorder. Post-infectious IBS (PI-IBS) is a subset of IBS that accounts for a large proportion of IBS patients. The PI-IBS symptoms meet the Rome criteria for IBS with diarrhoea (IBS-D) or IBS with mixed bowel habits (IBS-M). A low-grade inflammation has been reported to occur in PI-IBS. Abnormalities in intestinal endocrine cells have been reported in both sporadic IBS and PI-IBS.Case presentationA 20-year-old female with a diagnosis of IBS with constipation (IBS-C), according to Rome III criteria, contracted Campylobacter-induced gastroenteritis, after which her symptom pattern changed to IBS-M. She showed an intestinal low-grade inflammation that was manifested by an increase in the number of intraepithelial and lamina propria leucocytes and lymphocytes and an increase in the density of mast cells in lamina propria. There was also an increase in the density of intestinal serotonin and peptide YY (PYY) cells and a decrease in the density of rectal somatostatin cells. Follow-up of the patient at 4-months post-infection revealed reduction of IBS symptoms and an improvement in her quality of life. However, 6 months following the Campylobacter infection, the patient switched back from IBS-M to IBS-C, probably due to recovery from PI-IBS. The patient was treated with prucalopride, which is serotonin 5HT4 receptor agonist. Six months later following this treatment, the symptoms were reduced and the quality of life improved in the reported patient.ConclusionsGastroenteritis in patients with IBS-C causes a post-infectious, low-grade inflammation. Interaction between immune-cells and intestinal endocrine cells increases the density of certain endocrine cells, which in turn might be responsible for the change in the symptom pattern, the milder symptoms and the improvement in the quality of life seen in the reported patient. The findings in this case raise the question as to whether intestinal infections are responsible for the previously reported switching of IBS from one subtype to another over time.

Characterisation of faecal protease activity in irritable bowel syndrome with diarrhoea: origin and effect of gut transit

ObjectivesFaecal serine proteases (FSPs) may play a role in irritable bowel syndrome with diarrhoea (IBS-D), but their origin is unclear. We aimed to structurally characterise them and define the impact...