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The Impact of Somatization on the Use of Gastrointestinal Health-Care Resources in Patients with IBS new
      #215265 - 09/22/05 04:51 PM
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The American Journal of Gastroenterology
Volume 0 Issue 0 - October 2005
doi:10.1111/j.1572-0241.2005.00269.x


The Impact of Somatization on the Use of Gastrointestinal Health-Care Resources in Patients with Irritable Bowel Syndrome

Brennan M.R. Spiegel, M.D., M.S.H.S.14, Fasiha Kanwal, M.D., M.S.H.S.13, Bruce Naliboff, Ph.D.4, and Emeran Mayer, M.D.2,4

BACKGROUND: It is unclear why patients with irritable bowel syndrome (IBS) consume a disproportionate amount of health-care resources versus matched controls. One possibility is the presence of comorbid somatizationa process marked by multiple unexplained somatic complaints that is highly prevalent in IBS. We sought to determine whether higher levels of somatization are associated with higher levels of gastrointestinal (GI) resource utilization in IBS.

METHODS: A total of 1,410 patients >18 yr with IBS were evaluated at a university-based clinic. Subjects completed a symptom questionnaire, the SCL-90R psychometric checklist, and the SF-36 Health Survey. We measured two outcomes: (1) a 1-yr direct GI health-care costs and (2) a 1-yr number of GI physician visits. Our primary regressor was somatization as measured by the somatization subscale of the SCL-90R. We performed regression analyses to measure the adjusted influence of somatization on GI resource utilization.

RESULTS: In the full sample of patients, there were no differences in the likelihood of expending versus not expending previous GI health-care costs among groups with varying levels of somatization. Similarly, there were no differences in either the likelihood of visiting a GI physician or the number of overall physician visits among patients with varying levels of somatization. However, in the subset of patients expending at least $1.00 in GI costs in the previous year (53% of cohort), there was a significantly higher cost of care for subjects with high versus low levels of somatization.

CONCLUSIONS: IBS patients with high levels of somatization are not more likely to seek GI care compared to patients with low levels of somatization. However, once they are evaluated for care, patients with high somatization expend significantly more GI health-care costs. This suggests that somatization is positively associated with health-care costs in IBS, and that the association may be driven more by physicians than patients.

(Am J Gastroenterol 2005;100:112)

http://www.blackwell-synergy.com/doi/abs/10.1111/j.1572-0241.2005.00269.x

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Bronchial Hyperresponsiveness in Irritable Bowel Syndrome new
      #218944 - 10/11/05 01:16 PM
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Bronchial Hyperresponsiveness in Irritable Bowel Syndrome

Authors: Jun, Dae1; Lee, Oh2; Yoon, Ho3; Lee, Hang1; Yoon, Byung1; Choi, Ho1; Lee, Min1; Lee, Dong1; Kee, Choon1

Source: Digestive Diseases and Sciences, Volume 50, Number 9, September 2005, pp. 1688-1691(4)

Publisher: Kluwer Academic Publishers

< previous article ' next article > View Table of Contents

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Abstract:

Extraintestinal symptoms are often found in patients with irritable bowel syndrome (IBS). Recent studies suggest that IBS is associated with bronchial hyperresponsiveness. But it is still arguable that the bronchial hyperresponsiveness is associated with IBS patients. The purpose of this study is to investigate the possible relationship between IBS and bronchial hyperresponsiveness. Forty-two patients with IBS and 42 control subjects were included in this study. All patients underwent pulmonary function, methacholine challenge, and skin prick tests. There was no statistical difference between the two groups with respect to percentage of all pulmonary function test parameters, including FEV1%, FCV%, FVC/FEV1, and FEF25 - 75%. Only two persons in the alternating-type IBS patient group and one person in the control group tested positive in the methacholine provocation test. But all PC20 values were above 16 mg/ml. These results do not demonstrate a relationship between bronchial hyperresponsiveness and IBS. However, a relationship might exist in a subpopulation of IBS patients.

http://www.ingentaconnect.com/content/klu/ddas/2005/00000050/00000009/00002916;jsessionid=p8p8fwgtpbpy.victoria

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Childhood Abdominal Pain May Progress to Adult Irritable Bowel Syndrome new
      #218948 - 10/11/05 01:36 PM
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Childhood Abdominal Pain May Progress to Adult Irritable Bowel Syndrome




NEW YORK (Reuters Health) Sept 29 - Childhood abdominal pain is a common complaint, which may progress to adult irritable bowel syndrome (IBS) in some children, according to a study in the September issue of the American Journal of Gastroenterology.

"The natural history of childhood abdominal pain and its association with adult IBS remain poorly described," Dr. Nicholas J. Talley, of the Mayo Clinic College of Medicine, Rochester, Minnesota, and colleagues write.

To investigate, they assessed the characteristics of childhood abdominal pain over the first 11 years of life in some 1,000 children born in Dunedin, New Zealand in 1972, and examined the association of childhood abdominal pain with IBS at 26 years.

Three measures were used to describe history of childhood abdominal pain: medical service encounters for childhood abdominal pain, parental reports of stomach pain, and a composite measure including both medical encounters and parental report. Three time frames were examined: ages 0 to 7, 7 to 9, and 9 to 11 years. Data were available for 912 subjects.

A history of abdominal pain was documented in 18.1% of children. Childhood abdominal pain was more common in females than in males. Among males, the prevalence of childhood abdominal pain peaked at age 7 to 9 years, but the prevalence of childhood abdominal pain remained stable across assessments for females.

IBS at age 26 years was about 2 or 3 times more common among subjects with a history of childhood abdominal pain between the ages of 7 and 9 years compared with those with no history, depending on the assessment method.

Adjustment for sex, socioeconomic status, psychiatric disorder at age 26, childhood emotional distress, or maternal malaise did not alter this association.

"The emergence of multiple stressors in the home and school environment may present a plausible mechanism to account for these findings," Dr. Talley's team suggests. "The 7 to 9 year age period follows closely from the school starting age in many cultures, and children who are predisposed to stress-related disorders may be at particular risk of developing symptomatic complaints at this point."

Am J Gastroenterol 2005;100:2071-2078.


http://www.medscape.com/viewarticle/513761

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Functional Constipation Linked to Obesity in Children new
      #218949 - 10/11/05 01:43 PM
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Functional Constipation Linked to Obesity in Children

By Anthony J. Brown, MD

NEW YORK (Reuters Health) Sept 21 - Children with functional constipation are about twice as likely to be obese as their peers without this problem, according to a report in the September issue of Pediatrics.

"When a clinician sees a child with constipation, they should remember to evaluate them for obesity," lead author Dr. Dinesh S. Pashankar, from Yale University School of Medicine in New Haven, Connecticut, told Reuters Health. "As most people are aware, obesity is an increasing problem among children and unless there's an issue, like constipation, many obese children simply won't be seen by a clinician."

The new findings also have psychiatric implications, Dr. Pashankar emphasized. Individually, "obesity and constipation can cause behavioral issues and depression, but together the problem is likely to be more severe. Clinicians need to be aware of that."

In the current study, the researchers compared the prevalence of obesity among 719 children with functional constipation and among 930 control children.

The rate of obesity among the constipated children was 22.4%, nearly double the rate seen in control children -- 11.7%. The association between constipation and obesity was noted in both boys and girls and was not related to the presence of encopresis in constipated children.

The new findings generally support those of a previous study, which examined this topic but did not include a control group, Dr. Pashankar pointed out.

As to the mechanism linking obesity and constipation, Dr. Pashankar said that diet is likely a major factor. "Less fiber intake probably results in greater caloric intake and together these dietary patterns cause both problems."

Pediatrics 2005;116:e377-e380.

http://www.medscape.com/viewarticle/513186?src=mp

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Brain activation responses to auditory stimuli in IBS new
      #221825 - 10/28/05 11:42 AM
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Neurogastroenterology and Motility
Volume 0 Issue 0 - October 2005
doi:10.1111/j.1365-2982.2005.00720.x


Brain activation responses to subliminal or supraliminal rectal stimuli and to auditory stimuli in irritable bowel syndrome

v. andresen*, d. r. bach*, a. poellinger, c. tsrouya*, a. stroh, a. foerschler§, p. georgiewa, c. zimmer¶ & h. mönnikes*

Abstract

Visceral hypersensitivity in irritable bowel syndrome (IBS) has been associated with altered cerebral activations in response to visceral stimuli. It is unclear whether these processing alterations are specific for visceral sensation.

In this study we aimed to determine by functional magnetic resonance imaging (fMRI) whether cerebral processing of supraliminal and subliminal rectal stimuli and of auditory stimuli is altered in IBS. In eight IBS patients and eight healthy controls, fMRI activations were recorded during auditory and rectal stimulation.

Intensities of rectal balloon distension were adapted to the individual threshold of first perception (IPT): subliminal (IPT 10 mmHg), liminal (IPT), or supraliminal (IPT +10 mmHg). IBS patients relative to controls responded with lower activations of the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) to both subliminal and supraliminal stimulation and with higher activation of the hippocampus (HC) to supraliminal stimulation.

In IBS patients, not in controls, ACC and HC were also activated by auditory stimulation. In IBS patients, decreased ACC and PFC activation with subliminal and supraliminal rectal stimuli and increased HC activation with supraliminal stimuli suggest disturbances of the associative and emotional processing of visceral sensation.

Hyperreactivity to auditory stimuli suggests that altered sensory processing in IBS may not be restricted to visceral sensation.


http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2982.2005.00720.x

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Colonic Immune Activity and Blood T Lymphocytes in Patients With Irritable Bowel Syndrome new
      #221827 - 10/28/05 11:48 AM
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Clinical Gastroenterology and Hepatology
Volume 3, Issue 10 , October 2005, Pages 980-986

doi:10.1016/S1542-3565(05)00410-6

Copyright © 2005 American Gastroenterological Association Published by Elsevier Ltd.

A Controlled Study of Colonic Immune Activity and Blood T Lymphocytes in Patients With Irritable Bowel Syndrome

Lena Öhman , , Stefan Isaksson, Anna Lundgren§, Magnus Simrén and Henrik Sjövall

Department of Internal Medicine, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden
Department of Clinical Immunology, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden
Department of Medical Microbiology and Immunology, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden

Available online 6 October 2005.


Background & Aims: The mechanisms behind irritable bowel syndrome (IBS) are incompletely understood. Recently several studies have suggested a low-grade colonic inflammation as initiator of the gut dysfunctions recorded in this patient group. The aim of this study was to characterize the phenotype and homing properties of colonic and peripheral blood lymphocytes in patients with IBS.

Methods: Patients with IBS (n = 33), defined by the Rome II criteria, were compared with UC patients (n = 23) and control subjects (n = 15) without gastrointestinal symptoms. Colonic and peripheral blood lymphocytes were analyzed by flow cytometry. Secretion of IFN-&#947; from intestinal biopsies was determined by enzyme-linked immunosorbent assay, and immunohistochemical staining of colonic biopsies was performed. Results: IBS patients displayed an increased frequency of peripheral blood CD4+ and CD8+ T cells expressing the gut homing integrin &#946;7. Accordingly, IBS and UC patients had an augmented frequency of lamina propria CD8+ T cells in the ascending colon as compared with control subjects. The frequency of intestinal T cells expressing integrin &#946;7+ was unaltered in IBS and UC patients, although the expression of mucosal addressin cell adhesion molecule–1+ endothelium, the ligand for integrin &#946;7, was increased in the ascending colon of IBS and UC patients as compared with control subjects. Conclusions: Patients with IBS exhibit an enhanced immune activity in the gut and an increased frequency of integrin &#946;7+ T lymphocytes in the peripheral blood.

Our data further support the hypothesis of IBS being at least partially an inflammatory disorder.

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B7GGW-4H8FVBB-J&_user=10&_handle=V-WA-A-W-WD-MsSAYWW-UUA-U-AABAZEZWZZ-AAWEWDDUZZ-BEYWDYBWD-WD-U&_fmt=summary&_coverDate=10%2F31%2F2005&_rdoc=16&_orig=browse&_srch=%23toc%2320161%232005%23999969989%23607610!&_cdi=20161&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=238c088ffd280cc3f19386caee0a95f8

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Irritable Bowel Syndrome Study Shows That Targeted Antibiotics Lead To Long-lasting Improvement new
      #224504 - 11/12/05 01:00 PM
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Source: Cedars-Sinai Medical Center

Date: 2005-11-09

Irritable Bowel Syndrome Study Shows That Targeted Antibiotics Lead To Long-lasting Improvement In Symptoms

Researchers at Cedars-Sinai Medical Center have found that a nonabsorbable antibiotic – one that stays in the gut – may be an effective long-term treatment for irritable bowel syndrome (IBS), a disease affecting more than an estimated 20 percent of Americans. The findings, which showed that participants benefited from the antibiotic use even after the course of treatment ended, support previously published research identifying small intestine bacterial overgrowth (SIBO) as a possible cause of the disease.

The research was presented at the recent American College of Gastroenterology's annual meeting in Honolulu, HI.

"This study is important as it is the first to show that the use of targeted antibiotics results in a more significant and long-lasting improvement in IBS symptoms," said Mark Pimentel, M.D., first author on the study and director of the GI Motility Program at Cedars-Sinai. "These results clearly show that antibiotics offer a new treatment approach – and a new hope – for people with IBS."

The randomized, double blind study involved 87 patients. Those on the rifaximin experienced a 37 percent overall improvement of their IBS symptoms as compared to 23 percent on the placebo. Among study subjects whose primary symptom was diarrhea, those on the antibiotic showed more than twice the improvement of those on the placebo (49 percent vs. 23 percent). Patients received the drug (or placebo) for 10 days and were then followed for a total of 10 weeks. Participants kept a stool diary, took a questionnaire and were given methane breath tests. The positive effects of the drug were shown to continue throughout most of the 10-week study, not just during the actual antibiotic course.

Because the cause of IBS has been elusive, treatments for the disease have historically focused on reducing its symptoms – diarrhea and constipation – by giving medications that either slow or speed up the digestive process. In 2000, Pimentel linked bloating, the most common symptom of IBS, to bacterial fermentation, showing that small intestine bacteria overgrowth (SIBO) may be the causative factor in IBS (The American Journal of Gastroenterology, Dec. 2000).

To show evidence of small intestine bacterial overgrowth, participants in both studies were given a lactulose breath test, which monitors the level of hydrogen and methane (the gases emitted by fermented bacteria) on the breath. In the first study, an abnormal breath methane profile was shown to be 100 percent predictive of constipation-predominant IBS. In the current study, the correlation between the amount of methane and the amount of constipation was confirmed, another key finding.

"We were pleased – but not surprised – with the results of this study," said Pimentel. "The next step is to start larger, multi-centered studies to confirm the positive results of this study, which suggest that people can benefit from targeted antibiotic treatment for their IBS."

Irritable Bowel Syndrome is an intestinal disorder that causes abdominal pain or discomfort, cramping or bloating and diarrhea and constipation. It is a long-term condition that usually begins in adolescence or in early adult life. Episodes may be mild or severe and may be exacerbated by stress. It is one of the top ten most frequently diagnosed conditions among U.S. physicians and affects women more often than men.


###
Other authors from Cedars-Sinai include Sandy Park, B.A., Yuthana Kong M.P.H. and Robert Wade. Sunanda V. Kane from the University of Chicago also participated in the study.

Rifaximin is made by Salix Pharmaceuticals, Inc. Funding for the study was provided by Salix Pharmaceuticals, Inc.


--------------------------------------------------------------------------------

This story has been adapted from a news release issued by Cedars-Sinai Medical Center.

http://www.sciencedaily.com/releases/2005/11/051109181127.htm


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The Genetics of Irritable Bowel Syndrome new
      #224507 - 11/12/05 01:10 PM
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The Genetics of Irritable Bowel Syndrome

doi:10.1016/S1542-3565(05)00184-9
Copyright © 2005 American Gastroenterological Association Published by Elsevier Ltd.
Clinical genomics

The Genetics of Irritable Bowel Syndrome

Yuri A. Saito , Gloria M. Petersen‡, G. Richard Locke III; and Nicholas J. Talley

Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic and Foundation, Rochester, Minnesota, USA
‡Division of Epidemiology, Mayo Clinic and Foundation, Rochester, Minnesota, USA

Available online 2 November 2005.

Because of the heterogeneity in symptoms and diagnostic findings, patients with irritable bowel syndrome (IBS) remain a challenge to treat and to study. This difficulty stems from lack of understanding of the pathophysiology of this disorder.

Environmental factors likely play an important role in the pathogenesis and clinical manifestations of IBS. Several recent studies suggest a genetic basis for IBS, either in etiology or predicting response to therapy. Because of interest in studying the genetic contributors to this and other functional gastrointestinal disorders, we review the literature on genetic risk factors that might explain the familial clustering of IBS. Familial aggregation studies and twin studies suggest a modest contribution of genetics to the development of IBS. Pharmacogenomic and association studies provide stronger, although far from conclusive, evidence for genetic variants that affect expression of IBS. Together, these studies suggest that a multidisciplinary approach with clinical and psychological tools, epidemiologic methods, and genetic techniques might help elucidate the molecular components leading to the common symptoms of IBS and result in better treatments for those with IBS.



Clinical Gastroenterology and Hepatology
Volume 3, Issue 11 , November 2005, Pages 1057-1065

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B7GGW-4HG68V2-C&_user=10&_handle=V-WA-A-W-WC-MsSAYWA-UUW-U-AABBZAEWVD-AABAWUUUVD-VVEZVEUBZ-WC-U&_fmt=summary&_coverDate=11%2F30%2F2005&_rdoc=11&_orig=browse&_srch=%23toc%2320161%232005%23999969988%23609635!&_cdi=20161&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=4f28e1b14a3d1abbf03afcce4ac10050


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New Studies Gauge Knowledge, Attitudes and Preferences of Patients with Irritable Bowel Syndrome
      #224512 - 11/12/05 01:30 PM
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Contact: Monday, October 31, 2005

Anne-Louise Oliphant, ACG

New Studies Gauge Knowledge, Attitudes and Preferences of Patients with Irritable Bowel Syndrome -- Significant Percentage Mistakenly Believe IBS Causes Cancer -- -- More Information Could Allay Many Fears and Concerns --


HONOLULU, October 31, 2005 -- Significant misconceptions about the causes of their condition and mistaken beliefs about its potential progression into other diseases, including cancer, marks the knowledge of a sample of patients with Irritable Bowel Syndrome (IBS) in two recent studies by researchers at Dartmouth-Hitchcock Medical Center in New Hampshire.

Presented at the 70th Annual Scientific Meeting of the American College of Gastroenterology, these studies echo findings presented at ACG by Dr. Albena Halpert of Boston Medical Center and colleagues at the University of North Carolina at Chapel Hill on patient perceptions of IBS and their preferences about patient education.

Dartmouth-Hitchcock Study Finds Significant Concerns and Misconceptions "IBS is one of the most common medical conditions, and our study reveals that a lot of people are facing a problem, they don't feel well, they have significant concerns, and they don't have enough information," said Brian E. Lacy, Ph.D., M.D., one of the investigators at Dartmouth-Hitchcock who conducted two separate analyses of 261 respondents to study questionnaires.

In one analysis, Dr. Lacy and his colleagues found that almost half (42.9 percent) of respondents believed that IBS develops due to food allergy or intolerance, while an even larger percentage (82 percent) reported that a change in their daily routine causes IBS. Significant misconceptions were identified regarding the natural history of IBS, with one-third of respondents believing that once IBS develops it will never resolve, and 16.7 percent expressing the belief that IBS will turn into cancer. Of these patients, 87 percent reported that IBS
significantly affects their lives, with daily activities (40.1 percent), work life (19.3 percent) and social life (11.2 percent) being the most frequently affected.

In a related study of the same survey respondents, Dr. Lacy and his colleagues found that this sample of patients with IBS did not understand the causes of their condition. A large percentage cited dietary factors (80.7 percent), anxiety (87.9 percent), and depression (68.2) as the most frequent causes of IBS. IBS patients in this study believe that IBS increases the risk of colon cancer (21.5 percent) and increases the risk of Inflammatory Bowel Disease (30.5 percent).

IBD is an inflammatory condition of the intestine that can result in bleeding, fever, elevation of the white blood cell count, as well as diarrhea and cramping abdominal pain. IBD includes ulcerative colitis and Crohn's disease. "This is the first study to assess IBS patients' knowledge regarding their disorder.

Our findings highlight the need for effective educational programs for IBS patients," concluded Dr. Lacy. National Survey on Patient Education in IBS Albena Halpert, M.D. of Boston Medical Center and Douglas Drossman, M.D., FACG of the University of North Carolina at Chapel Hill developed and fielded a questionnaire to identify patients' perceptions about IBS, their preferences on the type of information they need, as well as educational media and expectations from health care providers.

Responses from 200 patients with IBS revealed misperceptions about IBS developing into other conditions, including colitis, malnutrition and cancer. This survey found IBS patients were most interested in learning about foods to avoid (60 percent), causes of IBS (55 percent), medications (58 percent), coping strategies (56 percent), and psychological factors related to IBS (55 percent). The respondents indicated that they wanted their physician to be available via phone or e-mail following a visit (80 percent) and have the ability to listen (80 percent), provide hope (73 percent) and support (63 percent).


About Irritable Bowel Syndrome IBS is a functional gastrointestinal (GI) disorder characterized by recurring symptoms of abdominal discomfort or pain associated with an altered bowel habit, either constipation, diarrhea, or both. More than 58 million people suffer from IBS, which affects more women (80%) than men. IBS is a real medical condition, but it is not life threatening, and will not lead to other serious diseases.

In IBS, the GI tract may function differently, processing more slowly (or more quickly) than the average person. While the cause of this different "pace" of the GI tract in IBS is not known, and there is no cure, there are usually ways to help manage specific symptoms. Physicians now have more scientific knowledge and an improved range of
treatment options that can provide relief for IBS sufferers.

The American College of Gastroenterology has resources for patients with IBS online at www.ibsrelief.org and free educational materials are available by calling ACG's toll-free hotline 866-IBS-RELIEF. About the American College of Gastroenterology The ACG was formed in 1932 to advance the scientific study and medical treatment of disorders of the gastrointestinal (GI) tract. The College promotes the highest standards in medical education and is guided by its commitment to meeting the needs of clinical gastroenterology practitioners.

Consumers can get more information on GI diseases through the following ACG-sponsored programs: • 1-800-978-7666 (free brochures on common GI disorders, including ulcer, colon cancer, gallstones, and liver disease) • 1-800-HRT-BURN (free brochure and video on heartburn and GERD) • www.acg.gi.org (ACG's Web site)

http://www.gi.org/media/releases/ACG05Release_IBSPatientKnowledgeAttitudes.pdf

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Clinical Insights in IBS-C and Chronic Constipation
      #230160 - 12/08/05 12:37 PM
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Medscape Clinical Insights in IBS-C and Chronic Constipation: An Expert Interview With Philip S. Schoenfeld, MD, MSEd, MSc

Posted 11/08/2005


Editor's Note:
Irritable bowel syndrome (IBS), a functional gastrointestinal disorder characterized by the interplay of altered motility, abnormal visceral sensation, and psychosocial factors, is one of the most common reasons for referral to a gastroenterologist. Chronic constipation is one of the most frequent gastrointestinal symptoms in the United States, accounting for nearly 2.5-2.7 million physician visits and 39,000-90,000 hospitalizations per year in the United States.

Constipation may be stratified, with considerable overlap, into issues of stool consistency vs defecatory behavior. A fundamental challenge to the treating physician derives from the fact that the term "constipation" has different meanings for different individuals and is therefore often subjectively defined, depending largely on a patient's perception of alterations in his or her bowel function. Thus, it is essential that the clinician understand not only the symptom-based criteria for chronic constipation but also the myriad other complaints and descriptors that patients may use to define their problem.

Indeed, it is the overlap in symptoms reported by patients with IBS with a predominant bowel complaint of constipation (IBS-C) and chronic constipation that poses a challenge in differential diagnosis.

Medscape spoke with Philip S. Schoenfeld, MD, MSEd, MSc, Assistant Professor of Medicine, University of Michigan School of Medicine, Ann Arbor; Chief, Division of Gastroenterology, Ann Arbor Veterans Affairs Medical Center, Ann Arbor, Michigan, to explore the impact of these clinically important gastrointestinal conditions on both the healthcare industry and patient alike, as well as to discuss the current state of the field regarding the management of IBS-C and chronic constipation, as framed by data presented during the 2005 annual meeting of the American College of Gastroenterology.

Medscape: Given the variety of descriptors that patients with chronic constipation may use to define their problem, and the varied clinical presentations of IBS, what should be the clinician's approach to working up the patient with the symptom of chronic constipation and to differentiating between IBS-C and chronic constipation, defining each as "real medical conditions" warranting treatment?

Dr. Schoenfeld: In the absence of alarm symptoms (eg, hematochezia, weight loss &#8805; 10 pounds, family history of colon cancer/inflammatory bowel disease), patients with symptoms of chronic constipation or IBS do not require invasive diagnostic testing before initiating therapy. Primary care physicians may obtain a complete blood cell count and a fecal occult blood test because these basic tests identify other alarm signs (eg, iron-deficiency anemia or occult gastrointestinal bleeding). However, patients with chronic constipation/IBS symptoms and healthy controls have a similar probability of having clinically important disorders (eg, hypothyroidism, colon cancer). There is one possible exception: celiac sprue may present with IBS symptoms (ie, abdominal discomfort associated with altered bowel habits). Depending on the prevalence of celiac sprue in the geographic area, primary care physicians and gastroenterologists may consider obtaining serologic tests for celiac sprue (ie, endomysial antibody and/or tissue transglutaminase antibody testing) in patients with IBS symptoms. Finally, all individuals 50 years of age and older should be offered a colonoscopy as part of routine colorectal cancer screening.

Chronic constipation and IBS-C are 2 syndromes that share many symptoms. Both conditions are characterized by infrequent bowel movements; a sense of incomplete evacuation; straining to pass stool; and passage of hard, pellet-like stools. However, the severity of bloating and abdominal discomfort differentiates IBS-C from chronic constipation. If a patient describes considerable abdominal discomfort or bloating with their constipation symptoms, then this patient should be diagnosed with IBS-C. Therefore, physicians should ensure that they specifically ask constipated patients about abdominal discomfort in order to differentiate IBS-C from chronic constipation. This is important because only tegaserod has demonstrated improvement in the multiple symptoms of IBS-C, whereas several therapies, including lactulose and psyllium, are effective at improving stool frequency and consistency in patients with constipation.[1]

Medscape: Given the uncertainty over what constitutes effective management for chronic constipation and the challenges in diagnosing and treating IBS-C, our therapeutic arsenal has continued to evolve, with the goal of providing alternative treatment options to help meet these growing needs. In this setting, 5-HT4 agonist therapy may offer an effective therapeutic alternative for these patients. What is the pathophysiologic rationale for targeting the serotonergic system in patients with chronic constipation and IBS-C?

Dr. Schoenfeld: IBS is an organic disorder, characterized by identifiable pathophysiologic changes, including alterations in interleukin (IL)-10/IL-12 ratios consistent with a proinflammatory state, defects in serotonin receptors, and abnormalities in visceral hypersensitivity.[1-3] In other words, IBS is not a "functional" disorder that can only be diagnosed after other organic disorders are ruled out with diagnostic tests. Although IBS is an organic disorder, we do not have a simple blood test or tissue test to make the diagnosis. Therefore, we must rely on symptom-based diagnoses as discussed previously.

Research regarding the pathophysiologic basis of IBS is a rapidly advancing field. Patients with IBS and patients with ulcerative colitis demonstrate defective serotonin receptors in enterochromaffin cells. This defect results in a decrease in the activity of serotonin, which is the primary neurotransmitter in the enteric nervous system. Thus, IBS patients suffer from a decreased level of activity in the enteric nervous system, which produces decreased smooth muscle motility and an increased sensitivity to mild distention in the colon (ie, visceral hypersensitivity). 5-HT4 receptor agonists, such as tegaserod, stimulate serotonin receptors in the enteric nervous system that are downstream from the enterochromaffin cell. In other words, these agents bypass the defective serotonin receptors and stimulate downstream receptors to "normalize" enteric nervous system activity. This stimulation increases colonic motility, which can provide relief of chronic constipation symptoms and IBS symptoms.[2,3]

Medscape: A study presented during the 70th Annual Meeting of the American College of Gastroenterology (ACG) looked at the long-term efficacy of the 5-HT4 receptor agonist tegaserod in maintaining symptom improvement in patients with chronic constipation. What can you tell us about this study and what were the key findings?

Dr. Schoenfeld: In this 13-month extension study, Shetzline and colleagues[4] followed chronic constipation patients who initially participated in a 12-week, placebo-controlled, double-blind randomized controlled trial (RCT) comparing tegaserod vs placebo. Abdominal distention, bloating, and bowel habits were assessed monthly. Those patients who responded to tegaserod in the initial RCT continued to demonstrate significant improvement compared with baseline for abdominal distention, bothersomeness of constipation, satisfaction with bowel habits, and global relief of constipation. All of these improvements were statistically significant. These data constitute the longest duration data on improvement in constipation symptoms with any therapy.

Medscape: During this year's meeting proceedings, Reilly and colleagues[5] presented the results of a trial conducted in women with IBS-C evaluating patients' overall satisfaction with initial and repeated use of tegaserod. What were the clinically important findings of this study, and what, in your opinion, are the implications for clinical practice?

Dr. Schoenfeld: Women with IBS-C were randomized to tegaserod 6 mg twice daily vs placebo in this double-blind randomized controlled trial. This was a unique trial because patients were asked whether the study medication was better than previously used medications and whether they would use the study medication in the future for treatment of their IBS symptoms. These questions were asked in addition to standard questions about satisfactory relief of abdominal discomfort, altered bowel habits, and global IBS symptoms. The authors demonstrated that patients using tegaserod experienced greater relief of abdominal discomfort, constipation, and global IBS symptoms compared with placebo. Furthermore, the patients (up to 76%) were significantly more likely to report that tegaserod was more effective than medications previously used (the authors did not provide a detailed list of "other medications" used by patients) for their IBS, and up to 85% stated that they would continue to use this agent for treatment of their IBS and/or recommend this treatment to fellow patients with IBS.

Medscape: Were there any other data presented during this year's meeting that would help put this information into clinical context? What's new on the therapeutic landscape?

Dr. Schoenfeld: Several new treatments for chronic constipation and IBS were discussed during this year's ACG meeting. Lubiprostone, which activates a chloride channel in the gastrointestinal tract, was examined in a double-blind, randomized placebo-controlled trial conducted in patients with chronic constipation.[6] In this 4-week trial, lubiprostone was found to be superior to placebo in terms of decreasing time to onset of first bowel movement and in increasing spontaneous bowel movement frequency. Patients treated with lubiprostone passed approximately 6 spontaneous bowel movements per week compared with placebo-treated patients who passed approximately 4 spontaneous bowel movements per week.

Additionally, in a double-blind randomized controlled trial involving female IBS patients, Quigley and colleagues[7] assessed the impact of a novel probiotic strain, Bifidobacteria infantis 35624, on bowel movement frequency. They found that the probiotic B infantis improved altered bowel habits in these patients with IBS. This is a particularly interesting avenue for further research because previous work reported by the same group of investigators demonstrated improvement in bloating in IBS patients using this probiotic.

References
American College of Gastroenterology Functional GI Disorder Task Force. An Evidence Based Approach to the Management of Irritable Bowel Syndrome in North America. Am J Gastroenterol. 2002;98:S1-S26.
Coates MD, Mahoney CR, Linden DR, et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology. 2004;126:1657-1664.
O'Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and Bifidobacterium in irritable bowel syndrome: Symptom responses and relationship to cytokine profiles. Gastroenterology. 2005;128:541-551.
Shetzline M, Dolker M, Bottoli I, et al. Patients with chronic constipation who respond to tegaserod after 4 weeks maintain symptom improvement for over 13 months. Am J Gastroenterol. 2005;100:S-339. [Abstract #927]
Reilly MC, Bracco A, McBurney CR, et al. IBS-C patients have greater treatment satisfaction with initial and repeated use of tegaserod. Am J Gastroenterol. 2005;100:S-339. [Abstract #926]
Johanson JF, Gargano MA, Holland PC, et al. Phase III study of lubiprostone, a chloride channel-2 (ClC2) activator for the treatment of constipation: safety and primary efficacy. Am J Gastroenterol. 2005;100:S-328. [Abstract #896]
Quigley EM, Whorwell PJ, Altringer J, et al. Probiotic use results in normalization of bowel movement frequency in IBS. Results froma clinical trial with the novel probiotic Bifidobacteria infantis 35624. Am J. Gastroenterol. 2005;100:S-326. [Abstract #888]


Funding Information

Supported by an independent educational grant from Novartis.

Philip S. Schoenfeld, MD, MSEd, MSc, Assistant Professor of Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan; Chief, Division of Gastroenterology, Ann Arbor Veterans Affairs Medical Center, Ann Arbor, Michigan


Philip S. Schoenfeld, MD, MSEd, MSc, has disclosed that he serves as a consultant to Novartis and GlaxoSmithKline. Dr. Schoenfeld has also disclosed that he serves on the speaker's bureau of Novartis.


Medscape Gastroenterology. 2005;7(2) ©2005 Medscape


http://www.medscape.com/viewarticle/515591

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