Irritable Bowel Syndrome: Schoenfeld P

Schoenfeld P, Anonymous00106. · Gastroenterology Outcomes Research, University of Michigan School of Medicine, Ann Arbor, USA. · MedGenMed. · Pubmed #14603112 links to  free full text

This publication has no abstract.

Schoenfeld P, Talley NJ. · No affiliation provided · Am J Gastroenterol. · Pubmed #16696786 No free full text.

Abstract: The treatment options for the irritable bowel syndrome (IBS) are expanding as new therapies, including probiotics and serotonin receptor agents, become available. Before any new agents gain widespread use, they must be studied in appropriately designed clinical trials. Symptom improvement remains the key clinically but the best technique to measure symptom improvement is unclear. Many IBS therapy studies have used a binary endpoint such as "Have you had satisfactory relief of your IBS symptoms in the past week? Yes/No?" The study by Whitehead and colleagues in this issue suggests that "satisfactory relief" is affected by baseline symptom severity and may not always truly reflect the symptom burden. Future research needs to determine whether "satisfactory relief" is truly adequate, or whether alternatives such as the proportion of patients achieving a > or = 50% reduction in symptom severity would represent a superior approach to capture clinically important improvement.

Spiegel B, Schoenfeld P, Naliboff B. · Division of Gastroenterology and Hepatology, VA Greater Los Angeles Healthcare System, CA, USA. · Aliment Pharmacol Ther. · Pubmed #17593064 No free full text.

Abstract: BACKGROUND: Chronic abdominal pain syndromes may increase the risk of suicidal behaviour - a feature well described in non-visceral pain syndromes. AIM: To perform a systematic review to summarize and interpret published data linking chronic abdominal pain syndromes and suicidal behaviour. METHODS: We performed a structured search to identify studies pertaining to the following questions: (i) What is the prevalence of suicidal behaviour in patients with chronic abdominal pain syndromes, including bowel syndrome (IBS)? (ii) Is the prevalence of suicidal behaviour in chronic abdominal pain syndromes higher than in matched controls? And (iii) is suicidal behaviour in abdominal pain syndromes simply due to psychiatric co-morbidities? RESULTS: Thirty-two relevant titles were identified, of which six manuscripts, describing eight studies, met inclusion criteria. Patients with non-IBS syndromes were 3-11 times more likely to demonstrate suicidal behaviour vs. controls, while patients with IBS were two to four times more likely to have suicidal behaviour. Chronic abdominal pain was an independent predictor of suicidal behaviour after adjusting for co-morbid psychiatric conditions. CONCLUSIONS: Chronic abdominal pain syndromes increase the risk for suicidal behaviours. This relationship may exist independently of co-morbid depression, although additional research is needed to better understand this link. These data indicate that clinicians should survey for suicidal behaviour in chronic abdominal pain patients.

Chang L, Chey WD, Harris L, Olden K, Surawicz C, Schoenfeld P. · Center for Neurovisceral Sciences & Women's Health, Department of Medicine, UCLA and VA Greater Los Angeles Healthcare Center, California, USA. · Am J Gastroenterol. · Pubmed #16606352 No free full text.

Abstract: BACKGROUND: Ischemic colitis and serious complications of constipation have been reported in association with the use of alosetron, which is approved for women with severe diarrhea-predominant IBS who have failed conventional therapies. This systematic review calculated the incidence of these adverse events in alosetron-using patients in clinical trials and post-marketing surveillance. METHODS: A panel of experts in epidemiology and functional bowel disorders reviewed clinical trial report forms and FDA MedWatch forms of each reported case of ischemic colitis or serious complications of constipation. Experts were blinded about whether patients used alosetron or placebo. Using pre-specified criteria, experts rated the likelihood of an accurate diagnosis and an association between medication use and adverse events. Cases that were not consistent with the reported diagnosis or not possibly associated with medication use were eliminated from calculation of incidence rates of adverse events. RESULTS: Pooled data from clinical trials indicate an increased rate of ischemic colitis among alosetron-using patients compared to placebo-using patients (0.15%vs 0.0%, respectively, p = 0.03), but there was no significant difference in the rate of serious complications of constipation. All (19/19) alosetron-using patients with ischemic colitis had reversible colitis without long-term sequelae. Based on post-marketing surveillance data, the post-adjudication rate of ischemic colitis is 1.1 per 1,000 patient-years of alosetron use and the rate of serious complications of constipation is 0.66 per 1,000 patient-years of alosetron use. CONCLUSION: The incidence of ischemic colitis and serious complications of constipation is very low and is rarely associated with long-term sequelae or serious morbidity.

Schoenfeld P. · Division of Gastroenterology, University of Michigan School of Medicine, VAMC 111-D, 2215 Fuller Road, Ann Arbor, MI 48105, USA. · Gastroenterol Clin North Am. · Pubmed #15862938 No free full text.

Abstract: Based on current evidence, bulking agents are not more effective than placebo at improving global irritable bowel syndrome (IBS)symptoms, although they may increase stool frequency in large doses. Tricyclic antidepressants are more effective than placebo for patients with diarrhea-predominant IBS. Imodium is more effective than placebo at improving stool consistency and decreasing stool frequency in patients with IBS, and it may be an important component for treating diarrhea-predominant IBS. Antispasmodics agents available in the United States are not more effective than placebo for treating IBS, although the studies are small and poorly designed. There are no randomized controlled trials examining the efficacy of laxatives for managing IBS. Tegaserod is more effective than placebo at improving global IBS symptoms in women with nondiarrhea-predominant IBS. Alosetron is more effective than placebo in women with diarrhea-predominant IBS, although its use should be limited to patients who have failed conventional therapy because of its adverse event profile.

Schoenfeld P. · Division of Gastroenterology, University of Michigan School of Medicine, Veterans Affairs Center for Excellence in Health Services Research, Ann Arbor, MI, USA. · Aliment Pharmacol Ther. · Pubmed #15521852 links to  free full text

Abstract: Gastrointestinal symptoms are the most common side-effects of tegaserod therapy. In data pooled from Phase III randomized controlled trials in patients with irritable bowel syndrome with constipation, diarrhoea was reported by 8.8% of patients treated with tegaserod 6 mg b.d. vs. 3.8% of patients treated with placebo. Similar rates were observed in international post-US marketing randomized controlled trials. In most patients, tegaserod-induced diarrhoea was mild and transient. In randomized controlled trials, it did not elicit fluid or electrolyte disturbances, and fewer than 3% of irritable bowel syndrome patients discontinued tegaserod due to diarrhoea. The incidence of other gastrointestinal symptoms (e.g. abdominal pain, nausea and flatulence) was similar in tegaserod-treated and placebo-treated patients. Pooled analysis of Phase III and post-US marketing randomized controlled trials did not demonstrate significant differences between tegaserod-treated and placebo-treated patients in the incidence of abdominal/pelvic surgery. No episodes of ischaemic colitis were reported in tegaserod-using patients in any Phase III or post-marketing randomized controlled trials, and post-marketing surveillance indicated that the rate of ischaemic colitis in tegaserod-using patients was lower than that in non-tegaserod-using patients. Pooled analysis of Phase III randomized controlled trials demonstrated an increase in the incidence of headaches in tegaserod-treated (6 mg b.d.) vs. placebo-treated patients (15% vs. 12.3%, respectively; P < 0.05), although post-US marketing randomized controlled trials did not demonstrate this increase. Other extra-gastrointestinal adverse events occurred with similar frequency in tegaserod-treated and placebo-treated patients. Tegaserod-treated patients in randomized controlled trials did not demonstrate significant prolongation of the QTc interval or cardiac arrhythmias compared with placebo-treated patients. In summary, tegaserod exhibits a favourable safety and tolerability profile in irritable bowel syndrome patients based on data from clinical trials.

Hasler WL, Schoenfeld P. · Division of Gastroenterology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA. · Drug Saf. · Pubmed #15230644 No free full text.

Abstract: This article reviews the safety and tolerability profile of tegaserod, a novel selective partial agonist of the serotonin 5-HT(4) receptor. Tegaserod was recently approved for the treatment of women with irritable bowel syndrome (IBS) with constipation.Tegaserod exhibits rapid absorption from the small intestine, and is excreted unchanged in the faeces and as metabolites in the urine. Meal ingestion decreases its bioavailability. There is little effect of age or gender on pharmacokinetics, although plasma levels may be slightly higher in the elderly. Tegaserod has no effect on plasma levels of other drugs metabolised by cytochrome P450 enzyme systems.Gastrointestinal symptoms are the most common adverse effects of tegaserod therapy. In data pooled from phase III randomised controlled trials (RCTs) in IBS with constipation patients, diarrhoea was reported by 8.8% of patients treated with tegaserod 6mg twice daily versus 3.8% of patients receiving placebo. Similar rates have been observed in international post-US marketing RCTs. In most patients, tegaserod-induced diarrhoea was mild and transient. In RCTs, it did not elicit fluid or electrolyte disturbances, and fewer than 3% of IBS patients discontinued tegaserod due to diarrhoea. Since its release, rare cases of more severe diarrhoea and ischaemic colitis have been reported. The incidence of other gastrointestinal symptoms (e.g. abdominal pain, nausea, and flatulence) has been similar among tegaserod-treated patients and placebo-treated patients. Pooled analysis of phase III RCTs and post-US marketing RCTs have not demonstrated significant differences between tegaserod-treated patients and placebo-treated patients in the incidence of abdominal-pelvic surgery. There is no convincing evidence that rebound gastrointestinal symptoms occur upon termination of tegaserod therapy.Pooled analysis of phase III RCTs demonstrated an increase in the incidence of headaches among tegaserod-treated patients (6mg twice daily) compared with placebo-treated patients (15% vs 12.3%, respectively, p < 0.05), although post-US marketing RCTs have not observed this increase. Other extra-gastrointestinal adverse events occur with similar frequency among tegaserod-treated patients and placebo-treated patients. Tegaserod-treated patients in RCTs have not demonstrated significant prolongation of the QTc interval or cardiac arrhythmias compared with placebo-treated patients. Supra-therapeutic doses in healthy volunteers did not effect electrocardiographic parameters. Laboratory parameters are mostly unaffected by tegaserod, although several individuals have exhibited increased eosinophil counts.In summary, tegaserod exhibits a favourable safety and tolerability profile in IBS patients based on data from clinical trials. Diarrhoea is the most common adverse event associated with tegaserod use. Continued post-US marketing surveillance will further define the safety and tolerability profile of tegaserod.

El-Serag HB, Pilgrim P, Schoenfeld P. · Division of Gastroenterology, Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX 77030, USA. · Aliment Pharmacol Ther. · Pubmed #15080847 links to  free full text

Abstract: BACKGROUND: The natural history of irritable bowel syndrome is unclear, including the likelihood that these patients will be diagnosed with an alternative organic or functional gastrointestinal disorder. Understanding the stability of an irritable bowel syndrome diagnosis may limit repeated diagnostic evaluation among these patients. METHODS: The inclusion criteria included observational longitudinal studies of clinic-based samples of adult patients with irritable bowel syndrome. Only studies published in the English language in full manuscript form were included. Literature searches, selection and review of eligible articles, and data abstraction were performed in a duplicate, independent manner. RESULTS: Fourteen studies met study selection criteria. In six studies with relevant information, 2-5% of irritable bowel syndrome patients were diagnosed with an alternative organic GI disorder after 6 months to 6 years of follow-up. Long-term follow-up indicated that 2-18% of patients developed worse irritable bowel syndrome symptoms, approximately 30-50% of patients had unchanged symptoms, and the rest either improved or had symptoms disappear. Prior surgery (one study), higher somatic scores (one study), higher baseline anxiety (two studies), depression scores (one study) were predictive of worsening of symptoms during long-term follow-up. CONCLUSIONS: Irritable bowel syndrome, a chronic disorder, is a stable diagnosis. Once initial investigations are negative, fewer than 5% are diagnosed with an alternative organic GI disorder. Repeated diagnostic evaluations of patients with recurrent or persistent symptoms similar to their baseline symptoms are not warranted.

Hasler WL, Schoenfeld P. · Division of Gastroenterology, University of Michigan School of Medicine, Ann Arbor, 48109, USA. · Aliment Pharmacol Ther. · Pubmed #12694081 links to  free full text

Abstract: AIM: To systematically review research on the prevalence of abdominal and pelvic surgery in patients with irritable bowel syndrome. METHODS: Computer searches of MEDLINE, EMBASE and Current Contents were performed independently by both investigators to identify appropriate studies. Primary study selection criteria included: (i) population-based samples of adult irritable bowel syndrome patients; (ii) the use of appropriate symptom-based criteria to identify irritable bowel syndrome patients; and (iii) comparison of the prevalence of abdominal and pelvic surgery in irritable bowel syndrome patients vs. control populations. Secondary analysis was performed on published studies of referral populations and case series. RESULTS: Two population-based studies met the primary study selection criteria and revealed an increased prevalence of surgery in irritable bowel syndrome patients vs. controls for cholecystectomy (4.6% vs. 2.4%, respectively; odds ratio, 1.9; 95% confidence interval, 1.2-3.2) and hysterectomy (18% vs. 12%, respectively; odds ratio, 1.6; 95% confidence interval, 1.1-2.2). Secondary analysis revealed an increased prevalence of appendectomy and other abdominal and pelvic surgery in irritable bowel syndrome patients. CONCLUSIONS: Irritable bowel syndrome is associated with a disproportionately high prevalence of abdominal and pelvic surgery, but most studies exhibit sub-optimal study design and do not define the factors causing the increased prevalence of surgery in these patients.

Brandt LJ, Bjorkman D, Fennerty MB, Locke GR, Olden K, Peterson W, Quigley E, Schoenfeld P, Schuster M, Talley N. · Albert Einstein College of Medicine, Bronx, NY, USA. · Am J Gastroenterol. · Pubmed #12425586 No free full text.

This publication has no abstract.

Cash BD, Schoenfeld P, Chey WD. · Division of Gastroenterology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA. · Am J Gastroenterol. · Pubmed #12425553 No free full text.

Abstract: OBJECTIVE: The aim of this study was to determine the pretest probability of organic GI disease and the accuracy of diagnostic tests for organic GI disease in patients who meet symptom-based criteria for irritable bowel syndrome (IBS). METHODS: After a comprehensive literature search for studies examining the accuracy of diagnostic tests for organic GI disease among patients who meet symptom-based criteria for IBS, two independent observers qualitatively assessed the methodology of selected studies and extracted data. Data on the pretest probability of organic GI disease in this population and the accuracy of currently recommended diagnostic tests were converted to descriptive tables. RESULTS: Among patients meeting symptom-based criteria for IBS, the pretest probability of inflammatory bowel disease, colorectal cancer, or infectious diarrhea is less than 1%. Currently recommended diagnostic tests rarely identify organic GI disease in patients fulfilling symptom-based criteria for IBS. However, the pretest probability of celiac disease in patients meeting symptom-based criteria for IBS was 10 times higher than the prevalence of celiac disease in the general population. CONCLUSIONS: There is insufficient evidence to recommend the routine performance of a standardized battery of diagnostic tests in patients who meet symptom-based criteria for IBS. Based upon the increased pretest probability of celiac disease, routine performance of serological tests for celiac disease may be useful in this patient population, though additional study is needed in this area.

Saito YA, Schoenfeld P, Locke GR. · Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA. · Am J Gastroenterol. · Pubmed #12190153 No free full text.

Abstract: OBJECTIVE: The aim of this study was to systematically review published literature about the prevalence, incidence, and natural history of irritable bowel syndrome (IBS) in North America. METHODS: A computer-assisted search of MEDLINE, EMBASE, and Current Contents/Science Edition databases was performed independently by two investigators. Study selection criteria included: 1) North American population-based sample of adults; 2) objective diagnostic criteria for IBS (i.e., Rome or Manning criteria); and 3) publication in full manuscript form in English. Eligible articles were reviewed in a duplicate and independent manner. Data extracted were converted into individual tables and presented in descriptive form. RESULTS: The prevalence of IBS in North America ranges from 3% to 20%, with most prevalence estimates ranging from 10% to 15%. The prevalences of diarrhea-predominant and constipation-predominant IBS are both approximately 5%. Published prevalence estimates by gender range from 2:1 female predominance to a ratio of 1:1. Constipation-predominant IBS is more common in female individuals. The prevalence of IBS varies minimally with age. No true population-based incidence studies or natural history studies were found. In one cohort surveyed on two occasions 1 yr apart, 9% of subjects who were free of IBS at baseline reported IBS at follow-up producing an onset rate of 67 per 1000 person-years. In all, 38% of patients meeting criteria for IBS did not meet IBS criteria at 1-yr follow-up. CONCLUSION: Approximately 30 million people in North America meet the diagnostic criteria for IBS. However, data about the natural history of IBS is quite sparse and renewed efforts should be focused at developing appropriately designed trials of the epidemiology of IBS.

Schoenfeld P, Chey WD. · Division of Gastroenterology, University of Michigan School of Medicine, Ann Arbor, MI, USA. · Clin Gastroenterol Hepatol. · Pubmed #15017675 No free full text.

This publication has no abstract.