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Biomedical subjects

William D Chey

Publications and source records attributed to William D Chey.

At least 19 recordsLinked to original sources
PubMed2006

Irritable bowel syndrome: update on colonic neuromuscular dysfunction and treatment.

Recent discoveries regarding the relatively autonomous workings of the enteric nervous system have expanded our understanding of the pathophysiology of irritable bowel syndrome (IBS). However, the heterogeneity of the pathogenesis of IBS continues to create unique challenges for clinicians who care for these patients. Advances in our understanding of the structure and functions of the brain-gut axis and its interplay with other potentially important factors, such as genetic predisposition, inflammation, and psychological unrest, have led to new developments in the field of targeted pharmacotherapy for IBS sufferers. Therapies designed specifically to modulate gut motility, secretion, and/or sensation have been created and introduced into the marketplace in recent years, and additional designer formulations are in various stages of development. Concurrently, new discoveries of potentially beneficial effects of agents approved for other, often non-gastroenterologic, conditions continue to be reported. This article reviews the accumulating body of evidence supporting the importance of neuromuscular dysfunction as a central cause of IBS symptoms and provides a rationale for the discussion of current and future drug development.

Colon↗
PubMed2006

Design of treatment trials for functional gastrointestinal disorders.

This document addresses the design of trials to assess the efficacy of new treatments for functional gastrointestinal disorders (FGID), emphasizing trials in irritable bowel syndrome and dyspepsia, because most research has been undertaken in these conditions. The double-blind, randomized, placebo-controlled, parallel group trial remains the preferred design. Randomized withdrawal designs, although encouraged by the European Agency for the Evaluation of Medicinal Products, have the same potential disadvantages as a crossover design, including carryover effects, unmasking (unblinding), and overestimation of the potential benefit for clinical practice. Innovative trial designs that evaluate intermittent (on demand) treatment are likely to become more common in the future. Investigators should include as broad a spectrum of patients as possible and should report recruitment strategies, inclusion/exclusion criteria, and attrition data. The primary analysis should be based on the proportion of patients in each treatment arm who satisfy an a priori treatment responder definition, or a prespecified clinically meaningful change in a patient-reported symptom improvement measure. Such measures of improvement are psychometrically validated subjective global assessments or a change from baseline in a validated symptom severity questionnaire. It is unethical to change the responder definition after a trial begins. Data analysis should address all patients enrolled, using an intention-to-treat principle. Reporting of results should follow the Consolidated Standards for Reporting Trials guidelines and include an analysis of harms data and secondary outcome measures to support or explain the primary outcome. Trials should be registered in a public location, prior to initiation, and should be published even if the results are negative or inconclusive.

Clinical Trials as Topic↗
PubMed2006

Functional bowel disorders.

Employing a consensus approach, our working team critically considered the available evidence and multinational expert criticism, revised the Rome II diagnostic criteria for the functional bowel disorders, and updated diagnosis and treatment recommendations. Diagnosis of a functional bowel disorder (FBD) requires characteristic symptoms during the last 3 months and onset > or =6 months ago. Alarm symptoms suggest the possibility of structural disease, but do not necessarily negate a diagnosis of an FBD. Irritable bowel syndrome (IBS), functional bloating, functional constipation, and functional diarrhea are best identified by symptom-based approaches. Subtyping of IBS is controversial, and we suggest it be based on stool form, which can be aided by use of the Bristol Stool Form Scale. Diagnostic testing should be guided by the patient's age, primary symptom characteristics, and other clinical and laboratory features. Treatment of FBDs is based on an individualized evaluation, explanation, and reassurance. Alterations in diet, drug treatment aimed at predominant symptoms, and psychotherapy may be beneficial.

Constipation↗
PubMed2006

Incidence of ischemic colitis and serious complications of constipation among patients using alosetron: systematic review of clinical trials and post-marketing surveillance data.

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.

Carbolines↗
PubMed2006

Levofloxacin-based triple therapy versus bismuth-based quadruple therapy for persistent Helicobacter pylori infection: a meta-analysis.

BACKGROUND: Levofloxacin-based triple therapy has been suggested as an alternative salvage therapy to bismuth-based quadruple therapy for persistent Helicobacter pylori (H. pylori) infection. METHODS: A search of PUBMED, EMBASE, EBM Review databases and abstracts from recent Digestive Disease Week, United European Gastroenterology Week, and European Helicobacter Study Group conferences was performed. Randomized controlled trials (RCTs) comparing levofloxacin-based triple salvage therapy (levofloxacin + amoxicillin + PPI) to bismuth-based quadruple salvage therapy (bismuth + tetracycline + metronidazole + PPI) were selected for meta-analysis. Additionally, all prospective trials evaluating this levofloxacin-based triple therapy as salvage therapy were pooled to analyze optimal levofloxacin treatment duration and dosing. All selected trials confirmed prior treatment failure and post-salvage treatment eradication. RESULTS: Four RCTs compared a 10-day regimen of levofloxacin-based triple therapy to 7-day bismuth-based quadruple therapy (n = 391 patients). Levofloxacin-based triple therapy was superior to quadruple therapy (RR = 1.41 [95% CI: 1.25-1.59]). Levofloxacin-based triple therapy was better tolerated than quadruple therapy with a lower incidence of side effects (RR = 0.51 [95% CI: 0.34-0.75]) and side effects prompting discontinuation of therapy (RR = 0.30 [95% CI: 0.10-0.89]). Eleven trials (n = 547 patients) evaluating levofloxacin-based triple therapy demonstrated higher eradication rates with 10-day versus 7-day regimen (87%[95% CI: 82%-92%]vs 68%[95% CI: 62%-74%]) yet eight trials (n = 477 patients) demonstrated no difference with 500 mg daily versus 250 mg b.i.d. dosing of levofloxacin (81%[95% CI: 78%-89%]vs 84%[95% CI: 66%-97%]). CONCLUSIONS: A 10-day course levofloxacin triple therapy is more effective and better tolerated than 7-day bismuth-based quadruple therapy in the treatment of persistent H. pylori infection.

Amoxicillin↗
PubMed2005

Clinical predictors of Barrett's esophagus length.

BACKGROUND: Assessment of clinical factors associated with Barrett's esophagus (BE) length remained within the realm of anecdotal reports or one center's experience. The aim of this multicenter study was to determine which clinical factors are highly correlated with the length of BE. METHODS: Patients diagnosed with BE were recruited into the study from 5 academic centers in the United States. All patients had an upper endoscopy that documented BE by the presence of intestinal metaplasia in biopsy specimens. All patients were evaluated by a validated demographic questionnaire and the GERD Symptom Checklist. RESULTS: A total of 263 patients with BE were recruited into the study. Mean BE length length for the entire sample was 4 +/- 3.3 cm. A longer hiatal hernia (r = 0.22, p < 0.01), any dysplasia (t = -2.3, p < 0.05), H2 receptor antagonist (H2-RA) consumption (t = 1.98, p < 0.05), and nonsmoking (t = -2.5, p < 0.05) were correlated with a longer segment of BE. Proton pump inhibitors (PPI) (t = 1.96, p < 0.05) were correlated with a shorter segment of BE. CONCLUSIONS: PPIs were correlated with shorter lengths of BE. In contrast, a longer hiatal hernia, any dysplasia, nonsmoking, or use of H2-RAs were correlated with a longer BE segment.

Adult↗
PubMed2005

Diagnosis of irritable bowel syndrome.

Because there are no reliable biological or laboratory markers associated with the condition, the diagnosis of irritable bowel syndrome(IBS) is based on patient descriptions of common symptoms such as abdominal pain accompanied by changes in stool form or frequency and associated symptoms such as bloating and distension. With the development and refinement of symptom-based criteria for the diagnosis of IBS, the traditional need for a negative diagnostic evaluation has been questioned. This article evaluates the diagnostic characteristics of various symptom-based criteria in routine clinical practice and reviews the data regarding the yield of the multiple commonly used diagnostic tests in patients with suspected IBS.

Abdomen↗
PubMed2005

Increased transduction of human intestinal epithelial cells by adenoviral vectors in inflammatory bowel disease.

BACKGROUND: Delivery of genes encoding anti-inflammatory proteins has been proposed as a strategy for the treatment of inflammatory bowel disease (IBD). The goal of this study was to assess the ability of a standard adenoviral vector to transfect epithelial cells in intestinal explants from patients with IBD compared with controls. METHODS: Endoscopic colon biopsies obtained from patients with no history of IBD and endoscopically normal colon (n = 4), patients with a history of ulcerative colitis (UC; n = 5), and patients with a history of Crohn's disease (CD; n = 3) were placed in explant culture and exposed to an adenoviral vector carrying the nuclear targeted beta-galactosidase reporter gene. RESULTS: X-Gal staining showed that the total number of transduced cells per square millimeter was greater in UC explants than in controls (mean, 11.3 versus 0.9 blue nuclei/mm, respectively; P < 0.02) and that the frequency of epithelial cell transduction was greater in UC explants than in controls (86% versus 47% of explants, respectively; P = 0.01). Transduction of mature columnar surface epithelial cells occurred exclusively in UC and CD explants and was not seen in controls. Attenuated epithelial cells at sites of tissue damage or ulceration showed increased transduction compared with mature columnar epithelial cells (62% versus 19% of occurrences, respectively; P < 0.0001). CONCLUSIONS: We conclude that intestinal epithelial cells from IBD patients are more readily transfected by standard adenoviral vectors than are those from control patients. These results suggest that targeting genes to inflamed intestine through the luminal route may be possible.

Adenoviridae↗
PubMed2005

Primary-care physicians' perceptions and practices on the management of GERD: results of a national survey.

BACKGROUND: Gastroesophageal reflux disease (GERD) is frequently managed by primary-care physicians (PCPs) although little is known about their current practices and management patterns. METHODS: We administered a questionnaire-based survey to PCPs attending sponsored educational conferences on GERD. Questionnaires were completed anonymously before the conferences and asked about prescribing patterns, indications for surgical referral, and issues concerning Barrett's esophagus and H. pylori infection. RESULTS: A total of 1046 completed questionnaires (97% acceptance rate) were received. Most PCPs prescribed a proton pump inhibitor (PPI) for GERD without prior authorization and without first using an H2-receptor antagonist (H2RA). Many gave an H2RA with once-daily PPI treatment for patients with nocturnal heartburn. Most referrals for anti-reflux surgery were for inadequate response to medical treatment, although PCPs usually first sought gastroenterological consultation. There was a widespread acceptance of screening GERD patients for Barrett's esophagus. There was general confusion about any relationship between H. pylori infection and GERD; 80% of PCPs tested for the infection in at least some patients who only had symptoms of GERD. CONCLUSIONS: Our survey has identified a number of areas of controversy and confusion related to the management of GERD. We hope that our findings can assist in the development of educational materials on GERD for PCPs.

Anti-Ulcer Agents↗
PubMed2005

Cilansetron: a new serotonergic agent for the irritable bowel syndrome with diarrhoea.

Cilansetron is a novel serotonin type-3 (5-hydroxytryptamine; 5-HT) receptor subtype 3 (5-HT(3)) receptor antagonist currently being evaluated for the treatment of female and male patients with irritable bowel syndrome with diarrhoea predominance (IBS-D). 5-HT(3) receptor antagonists such as cilansetron have been shown to affect gastrointestinal motility. Whether cilansetron affects visceral sensation independent of effects on visceral compliance remains controversial. Results from two large, randomised, double-blind, placebo-controlled, parallel-group Phase III clinical trials of cilansetron in patients with IBS-D have recently been presented in abstract form. These studies found that cilansetron was more effective than placebo at improving overall, as well as individual symptoms, including abdominal pain and diarrhoea in female and male IBS-D patients. The most commonly reported side effect with cilansetron has been constipation and, in general, the drug has been well tolerated in clinical trials. Although rare, the most concerning side effect observed with cilansetron has been suspected ischaemic colitis. The event rate for suspected ischaemic colitis associated with cilansetron from clinical trials is 3.77 per 1000 person years of exposure. This rate appears to be greater than that expected in the IBS population and similar to that observed with alosetron, another 5--HT(3) receptor antagonist. All of the cases of suspected ischaemic colitis reported with cilansetron have resolved without serious sequelae. How issues surrounding the safety of cilansetron will affect the approval process in various countries remains to be determined. However, the risk-benefit of cilansetron is likely to be most favourable in patients with IBS-D who have failed to respond to conventional medical therapies. A detailed risk management plan and post-marketing surveillance programme will be required should this drug become available for the treatment of patients with IBS-D.

Carbazoles↗
PubMed2005

A clinician's guide to managing Helicobacter pylori infection.

Helicobacter pylori infection is chronic and very common. Its clinical consequences vary widely, ranging from being asymptomatic and clinically insignificant in many cases to causing dyspepsia, peptic ulcer disease, and gastric malignancy in others. Care must be used in deciding whom to test for H pylori infection, as a positive result mandates treatment, making broad-based screening impractical.

Amoxicillin↗
PubMed2004

Endoscopy-negative reflux disease: concepts and clinical practice.

Endoscopy-negative reflux disease is used to describe a heterogeneous group of disorders with symptoms that mimic those of gastroesophageal reflux disease in the absence of visible esophageal injury at endoscopy. Compared with patients who have gastroesophageal reflux-related erosive esophagitis, those with endoscopy-negative disease are more likely to be younger, female, of lower body weight, and without a hiatal hernia. Approximately 50% of those with endoscopy-negative reflux have abnormal intraesophageal acid exposure and are considered to have nonerosive acid reflux disease. Those with symptoms of >12 consecutive or intermittent weeks' duration during the prior year, with normal acid exposure and without achalasia or other motility disorder with a recognized pathologic basis, are considered to have functional heartburn. In the absence of pathologic reflux, a number of etiologies may contribute to the symptoms of heartburn, including motor events, reflux of nonacidic gastric contents, minute changes in intraesophageal pH (pH <4), visceral hypersensitivity, and emotional or psychological abnormalities. Although persons with endoscopy-negative reflux disease experience decrements in their quality of life that are similar to those for individuals with erosive esophagitis, the response to traditional therapies for acid reflux may differ between the 2 groups. Studies have found that approximately 50% of patients with endoscopy-negative reflux disease experience complete symptom relief after 4 weeks of proton pump inhibitor treatment. In those with persistent heartburn symptoms, other structural or nonacid reflux etiologies for their symptoms should be explored.

Diagnosis, Differential↗
PubMed2004

Effect of tegaserod in chronic constipation: a randomized, double-blind, controlled trial.

BACKGROUND AND AIMS: Chronic constipation is a common gastrointestinal disorder. The aim of this study was to evaluate the efficacy, safety, and tolerability of tegaserod, a serotonin subtype 4 receptor partial agonist in patients with chronic constipation. METHODS: This was a randomized, double-blind, placebo-controlled study. After a 2-week baseline, patients received tegaserod 2 mg twice daily (n = 450), tegaserod 6 mg twice daily (n = 451), or placebo (n = 447) for 12 weeks, followed by a 4-week withdrawal period. Responders were those patients having been treated for at least 7 days with an increase of > or =1 complete spontaneous bowel movement/week vs. baseline during weeks 1-4 (primary variable) and weeks 1-12 (secondary variable). Other secondary variables included patient assessment of constipation symptoms (number of bowel movements, stool form, abdominal bloating/distention, straining, and abdominal pain/discomfort), and global assessment of constipation and bowel habits. RESULTS: Responder rates for complete spontaneous bowel movement during weeks 1-4 were significantly greater ( P < 0.0001) in the tegaserod 2 mg twice daily (41.4%) and 6 mg twice daily groups (43.2%) vs. placebo (25.1%). This effect was maintained over 12 weeks. Statistically significant improvements over placebo were observed across the majority of secondary variables for both tegaserod doses. No rebound effect was observed after treatment withdrawal. Tegaserod was well tolerated; headache and nasopharyngitis, the most frequent adverse events, were more common in the placebo group than in either tegaserod group. CONCLUSIONS: Over 12 weeks, tegaserod treatment produced significant improvements in chronic constipation symptoms and was also safe and well tolerated.

Chronic Disease↗
PubMed2004

Ulcerative colitis associated enteritis: is ulcerative colitis always confined to the colon?

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon whose etiology is unknown. Small bowel involvement in UC is extraordinarily rare, and should make the clinician question the diagnosis. However, we present a case of a 38-year-old man with voluminous diarrhea following colectomy for well-documented UC; he was found to have ulcerative enteritis with histologic features identical to UC. Also, for the first time, we present an inclusive review of another 11 cases of UC associated enteritis (UCAE) reported in the literature, and discuss the significance of the entity. We conclude that UC is rarely accompanied by enteritis that is distinct from Crohn disease, frequently presents shortly after colectomy, and usually is responsive to traditional therapies for inflammatory bowel disease (IBD).

Adolescent↗