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Biomedical subjects

W D Chey

Publications and source records attributed to W D Chey.

At least 19 recordsLinked to original sources

Review article: current and emerging therapies for functional dyspepsia.

Functional dyspepsia represents a heterogeneous group of gastrointestinal disorders marked by the presence of upper abdominal pain or discomfort. Although its precise definition has evolved over the last several decades, this disorder remains shrouded in controversy. The symptoms of functional dyspepsia may overlap with those of other functional bowel disorders including irritable bowel syndrome and non-erosive reflux disease. There may be coexistent psychological distress or disease complicating its presentation and response to therapy. Given the prevalence and chronicity of functional dyspepsia, it remains a great burden to society. Suspected physiological mechanisms underlying functional dyspepsia include altered motility, altered visceral sensation, inflammation, nervous system dysregulation and psychological distress. Yet the exact pathophysiological mechanisms that cause symptoms in an individual patient remain difficult to delineate. Numerous treatment modalities have been employed including dietary modifications, pharmacological agents directed at various targets within the gastrointestinal tract and central nervous system, psychological therapies and more recently, complementary and alternative treatments. Unfortunately, to date, all of these therapies have yielded only marginal results. A variety of emerging therapies are being developed for functional dyspepsia. Most of these therapies are intended to normalize pain perception and gastrointestinal motor and reflex function in this group of patients.

Antacids↗

Primary care physician perceptions of non-steroidal anti-inflammatory drug and aspirin-associated toxicity: results of a national survey.

AIM: To assess primary care physician perceptions of non-steroidal anti-inflammatory drug (NSAID) and aspirin-associated toxicity. METHODS: A group of gastroenterologists and internal medicine physicians created a survey, which was administered via the Internet to a large number of primary care physicians from across the US. RESULTS: One thousand primary care physicians participated. Almost one-third of primary care physicians recommended 325 mg rather than 81 mg of aspirin/day for cardioprotection. Fifty-nine percent thought enteric-coated or buffered aspirin reduced the risk of upper gastrointestinal (GI) bleeding. Seventy-six percent believed that Helicobacter pylori infection increased the risk of NSAID ulcers but fewer than 25% tested NSAID users for this infection. More than two-thirds were aware that aspirin co-therapy decreased the GI safety benefits of the cyclo-oxygenase 2 selective NSAIDs. However, 84% felt that aspirin with a cyclo-oxygenase 2 selective NSAID was safer than aspirin with a non-selective NSAID. When presented a patient at high risk for NSAID-related GI toxicity, almost 50% of primary care physicians recommended a proton pump inhibitor and cyclo-oxygenase 2 selective NSAID. CONCLUSIONS: This survey has identified areas of misinformation regarding the risk-benefit of NSAIDs and aspirin and the utilization of gastroprotective strategies. Further education on NSAIDs for primary care physicians is warranted.

Adult↗

Evaluation of the Ez-HBT Helicobacter blood test to establish Helicobacter pylori eradication.

BACKGROUND: The urea blood test (Ez-HBT) has been shown to compare favourably with the urea breath test in the diagnosis of active Helicobacter pylori infection. AIM: To examine the performance characteristics of the Ez-HBT Helicobacter blood test in establishing success or failure of therapy in H. pylori-infected adults using the 13C urea breath test as the reference method. METHODS: 13C urea breath test and Ez-HBT Helicobacter blood test were performed 4-6 weeks after completion of treatment in H. pylori positive subjects. Basal urea breath samples were collected; basal Ez-HBT Helicobacter blood test samples were not. Ez-HBT Helicobacter blood test results were reported as positive, negative, or indeterminate. RESULTS: Seventy patients generated 126 measurable sets of urea breath and blood tests. The H. pylori cure rate was 93%. The sensitivity, specificity, and accuracy of the Ez-HBT Helicobacter blood test were 100%, 97%, and 97%, respectively. Six of eight false positive and indeterminate Ez-HBT Helicobacter blood test results could be attributed to incomplete fasting or a 13C enriched diet. After correcting for the non-fasting state, the positive predictive value of the Ez-HBT Helicobacter blood test improved from 56% to 86%. CONCLUSION: The performance characteristics of the Ez-HBT Helicobacter blood test are comparable with that of 13C-urea breath test in establishing H. pylori eradication after therapy. Errors related to incomplete fasting can be mitigated by collection of a basal blood sample.

Adult↗

Review article: The role of serotonergic agents in the treatment of patients with primary chronic constipation.

Chronic constipation is a highly prevalent disorder that is associated with significant direct and indirect costs and has substantial impact on patient quality of life. It is more common among women and non-white populations and is evenly distributed across adult age groups. Constipation is a heterogeneous disorder associated with multiple symptoms and aetiologies. Recent research has increased our understanding of the pathogenesis of this disorder and the central role of the neurotransmitter serotonin in mediating gastrointestinal motility, secretion and sensation. Abnormal serotonin signalling and reuptake appear to play central roles in the symptoms of a subset of patients with chronic constipation. This observation provides a rationale for the use of targeted serotonergic agents for the treatment of chronic constipation. As the role of serotonin in gastrointestinal function is further elucidated and additional candidate drugs are developed, it is likely that serotonergic agents will afford additional treatment options for patients with chronic constipation. This article provides a concise review of the evidence supporting a role for serotonin in the pathogenesis of chronic constipation and a summary of the currently available evidence supporting the use of serotonergic agents for this disorder.

Brain↗

Effect of acute acoustic stress on anorectal function sensation in healthy human.

Little is known about the effects of acute acoustic stress on anorectal function. To determine the effects of acute acoustic stress on anorectal function and sensation in healthy volunteers. Ten healthy volunteers (7 M, 3 F, mean age 34 +/- 3 years) underwent anorectal manometry, testing of rectal compliance and sensation using a barostat with and without acute noise stress on separate days. Rectal perception was assessed using an ascending method of limits protocol and a 5-point Likert scale. Arousal and anxiety status were evaluated using a visual analogue scale. Acoustic stress significantly increased anxiety score (P < 0.05). Rectal compliance was significantly decreased with acoustic stress compared with control P (P < 0.000001). In addition, less intraballoon volume was needed to induce the sensation of severe urgency with acoustic stress (P < 0.05). Acoustic stress had no effect on hemodynamic parameters, anal sphincter pressure, threshold for first sensation, sensation of stool, or pain. Acute acoustic stimulation increased anxiety scores, decreased rectal compliance, and enhanced perception of severe urgency to balloon distention but did not affect anal sphincter pressure in healthy volunteers. These results may offer insight into the pathogenesis of stress-in-induced diarrhoea and faecal urgency.

Acoustic Stimulation↗

Irritable bowel syndrome - an evidence-based approach to diagnosis.

Irritable bowel syndrome (IBS) represents one of the most common reasons for primary care visits and consultation with a gastroenterologist. It is characterized by abdominal discomfort, bloating and disturbed defecation in the absence of any identifiable physical, radiologic or laboratory abnormalities indicative of organic gastrointestinal disease. IBS is a costly disorder, responsible for significant direct and indirect costs to patients and society. Much of the cost attributed to IBS arises from the time and resources used to establish the diagnosis. Historically IBS has been viewed by many as a diagnosis of exclusion rather than as a primary diagnosis, and many patients with typical symptoms will undergo an extensive array of diagnostic tests and procedures prior to the eventual diagnosis of IBS. Recent reviews addressing the management of such patients have cast doubt on the necessity for this degree of testing. Current best evidence does not support the routine use of blood tests, stool studies, breath tests, abdominal imaging or lower endoscopy in order to exclude organic gastrointestinal disease in patients with typical IBS symptoms without alarm features. Serological testing for celiac sprue in this population may eventually prove useful but validation of studies indicating an increased prevalence of this disease in patients with suspected IBS is needed. The development and refinement of symptom-based criteria defining the clinical syndrome of IBS has greatly facilitated the diagnosis of this condition, which can be confidently diagnosed through the identification of typical symptoms, normal physical examination and the exclusion of alarm features. The presence of alarm features or persistent non-response to symptom-directed therapies should prompt a more detailed diagnostic evaluation dictated by the patient's predominant symptoms.

Breath Tests↗

Review article: uninvestigated dyspepsia and non-ulcer dyspepsia-the use of endoscopy and the roles of Helicobacter pylori eradication and antisecretory therapy.

Due to its prevalence, impact on quality-of-life and the associated significant health resource utilization, dyspepsia is a major healthcare concern. The available management strategies for uninvestigated dyspepsia include prompt endoscopy, the 'test-and-treat' strategy for Helicobacter pylori, and empiric antisecretory therapy. There is consensus that endoscopy should be reserved for patients with alarm features (e.g. symptom onset after 45 years of age, recurrent vomiting, weight loss, dysphagia, evidence of bleeding, anaemia), H. pylori-positive individuals who fail test-and-treat, and those with an inadequate response to empiric antisecretory therapy. Factors influencing the decision between test-and-treat and empiric antisecretory therapy in uninvestigated dyspepsia include the local prevalence of H. pylori and peptic ulcer disease and the proportion of ulcers attributable to H. pylori. For uninvestigated dyspepsia in patients without alarm features, test-and-treat is the preferred initial management method in Europe based on the relatively high prevalence of H. pylori/peptic ulcer disease whereas empiric antisecretory therapy is preferred in many parts of the United States, where the prevalence of H. pylori/peptic ulcer disease is relatively low. In patients with non-ulcer dyspepsia, H. pylori eradication and empiric antisecretory therapy result in comparable and small, but statistically significant, improvements in dyspepsia. Empiric antisecretory therapy is the preferred initial method of managing non-ulcer dyspepsia in Europe and the US. The test-and-treat approach would receive increased enthusiasm if H. pylori cure is shown to prevent development of gastric cancer in non-ulcer dyspepsia patients in a large Western trial.

Algorithms↗

Review article: tegaserod -- the global experience.

Studies from the Western hemisphere have established the efficacy and safety of tegaserod in women with irritable bowel syndrome and constipation. This review summarizes the results of recent studies from around the world that confirm the efficacy and safety of tegaserod, and expand our understanding of the role of this drug in the treatment of patients with irritable bowel syndrome.

Adult↗

Reappraisal of non-invasive management strategies for uninvestigated dyspepsia: a cost-minimization analysis.

BACKGROUND: The benefits of the Helicobacter pylori test-and-treat strategy are attributable largely to the cure of peptic ulcer disease while limiting the use of endoscopy. AIM: To reappraise the test-and-treat strategy and empirical proton pump inhibitor therapy for the management of uninvestigated dyspepsia in the light of the decreasing prevalence of H. pylori infection, peptic ulcer disease and peptic ulcer disease attributable to H. pylori. METHODS: Using a decision analytical model, we estimated the cost per patient with uninvestigated dyspepsia managed with the test-and-treat strategy ($25/test; H.pylori treatment, $200) or proton pump inhibitor ($90/month). Endoscopy ($550) guided therapy for persistent or recurrent symptoms. RESULTS: In the base case (25%H. pylori prevalence, 20% likelihood of peptic ulcer disease, 75% of ulcers due to H.pylori), the cost per patient is $545 with the test-and-treat strategy and $529 with proton pump inhibitor, and both strategies yield similar clinical outcomes at 1 year. H. pylori prevalence, the likelihood of peptic ulcer disease and the proportion of ulcers due to H.pylori are important determinants of the least costly strategy. At an H. pylori prevalence below 20%, proton pump inhibitor is consistently less costly than the test-and-treat strategy. CONCLUSIONS: As the H. pylori prevalence, the likelihood of peptic ulcer disease and the proportion of ulcers due to H. pylori decrease, empirical proton pump inhibitor becomes less costly than the test-and-treat strategy for the management of uninvestigated dyspepsia. Given the modest cost differential between the strategies, the test-and-treat strategy may be favoured if patients without peptic ulcer disease derive long-term benefit from H.pylori eradication.

Anti-Bacterial Agents↗

Testing for Helicobacter pylori in the clinical setting.

There are a variety of tests available to identify Helicobacter pylori infection. These tests can be divided into those that do not require and those that do require endoscopy. This review provides a detailed discussion of the available diagnostic tests for H. pylori infection. Special attention is paid to the role of diagnostic testing in the management of patients with H. pylori-related disease. The potential advantages and disadvantages of various tests and the role of testing to confirm eradication after treatment for H. pylori is also discussed.

Antibodies, Bacterial↗

Noninvasive Helicobacter pylori testing for the "test-and-treat" strategy: a decision analysis to assess the effect of past infection on test choice.

BACKGROUND: Clinical guidelines support a noninvasive Helicobacter pylori "test-and-treat" strategy for individuals with uncomplicated dyspepsia. However, consensus is lacking regarding the preferred noninvasive testing method. OBJECTIVE: To use decision analytic modeling to estimate the clinical and economic outcomes associated with noninvasive tests designed to detect either H pylori antibody or active H pylori infection. DESIGN: Decision analytic model. PATIENTS: A simulated patient cohort with uncomplicated dyspepsia. INTERVENTIONS: The simulated dyspepsia cohort underwent antibody testing or testing to detect active H pylori infection (active testing). Individuals testing positive received eradication therapy. MAIN OUTCOME MEASURES: Appropriate and inappropriate treatment prescribed, cost per patient treated, incremental cost per unnecessary treatment avoided. RESULTS: Active testing led to a substantial reduction in unnecessary treatment for patients without active infection (antibody, 23.7; active, 1.4 per 100 patients) at an incremental cost of $37 per patient. The clinical advantage and cost-effectiveness of active testing was enhanced as the percentage of individuals with a positive antibody test result from past, but not current, infection increased. CONCLUSIONS: Active testing for H pylori infection significantly decreases the inappropriate use of antimicrobial therapy when compared with antibody testing. The advantages of active testing should be enhanced as the widespread use of antimicrobial agents increases the proportion of patients with antibody to H pylori, but without active infection.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Effect of meal size and test duration on gastric emptying and gastric myoelectrical activity as determined with simultaneous [13C]octanoate breath test and electrogastrography in normal subjects using a muffin meal.

Our purpose was to determine the effect of meal size on gastric emptying (GE) as measured by octanoate breath test (OBT), to determine the effect of the duration of breath collections on assessment of GE by OBT, and to determine the effect of meal size on gastric myoelectrical activity as measured by electrogastrography (EGG). Fourteen normal subjects underwent two modified [13C]OBTs using muffin meals of 250 or 350 kcal mixed with 100 mg [13C]sodium octanoate. T(1/2) for GE was determined for both the entire postprandial 6-hr breath collection and a truncated initial 4-hr data set. EGG was recorded for 30 min prior to the muffin meal and 4 hr postprandially. Using the 6-hr breath collection data, the T(1/2) was 177 +/- 7 (mean +/- SEM) for the 350-kcal meal compared to 153 +/- 7 min (P < 0.01) for the 250-kcal meal. Using the 4-hr data, the T(1/2) for the 350-kcal meal was 244 +/- 32 min compared to 165 +/- 12 min (P < 0.05) for the 250-kcal meal. The ratio of postprandial to fasting EGG power of the dominant frequency for the 350-kcal meal (1.9 +/- 0.4) was higher than that for the 250-kcal meal (1.3 +/- 0.6). T(1/2) for the 350-kcal meal using 4- and 6-hr data was significantly correlated with the 4-hr power ratio (r = 0.68 and 0.67; P < 0.05, respectively), but poorly correlated for the 250-kcal meal. In conclusions, GE and EGG are affected by meal size. Using the muffin-based [13C]OBT, T(1/2) for the 350-kcal meal was significantly longer than for a 250-kcal meal. Longer T(1/2) values were obtained with shorter breath sampling durations. The postprandial to fasting power ratio for the 350-kcal meal was greater than that for the 250-kcal meal.

Adult↗

Gastric distention correlates with activation of multiple cortical and subcortical regions.

BACKGROUND & AIMS: The pathophysiology of functional dyspepsia may involve abnormal processing of visceral stimuli at the level of the central nervous system. There is accumulating evidence that visceral and somatic pain processing in the brain share common neuronal substrates. However, the cerebral loci that process sensory information from the stomach are unknown. The aim of this study was to localize the human brain regions that are activated by gastric distention. METHODS: Brain (15)O-water positron emission tomography was performed in 15 right-handed healthy volunteers during baseline and distal gastric distentions to 10 mm Hg, 20 mm Hg, threshold pain, and moderate pain. Pain, nausea, and bloating were rated during baseline and distentions (0-5 scale). Statistical subtraction analysis of brain images was performed between distentions and baseline. RESULTS: Symptoms increased with distending stimulus intensity (maximum pain, 2.1 +/- 0.4; nausea, 2.2 +/- 0.4; bloating, 3.7 +/- 0.2). Paralleling increases in distention stimulus and symptoms, progressive increases in activation (P < or = 0.05), were observed in the thalami, insula bilaterally, anterior cingulate cortex, caudate nuclei, brain stem periaqueductal gray matter, cerebellum, and occipital cortex. CONCLUSIONS: Symptomatic gastric distention activates structures implicated in somatic pain processing, supporting the notion of a common cerebral pain network.

Adult↗

Intragastric acidification reduces the occurrence of false-negative urea breath test results in patients taking a proton pump inhibitor.

OBJECTIVE: The aim of this study was to investigate whether reducing intragastric pH, at the time of urea ingestion, decreases the likelihood of false-negative (FN) urea breath test (UBT) results in patients taking a proton pump inhibitor (PPI). METHODS: Patients with active Helicobacter pylori infection underwent a baseline 14C-UBT (UBT-1) followed by treatment with lansoprazole 30 mg/day for 14 to 16 days. On day 13, patients returned for a repeat standard UBT (UBT-2). Between days 14 to 16, patients underwent a modified UBT (UBT-3), which included consuming 200 ml of 0.1 N citrate solution 30 min before and at the time of 14C-urea administration. Breath samples were collected 10 and 15 min after 14C-urea ingestion. Mean 14CO2 excretion and the number of FN and equivocal UBT results were compared for the three UBTs. RESULTS: A total of 20 patients completed the study. Lansoprazole caused a significant decrease in mean breath 14CO2 excretion (disintegrations per minute) between UBT-1 (2.96 +/- 0.23) and UBT-2 (2.08 +/- 0.52, p < 0.05). Lansoprazole caused six (30%) FN and eight (40%) equivocal UBT-2 results. Mean breath 14CO2 excretion for UBT-3 (677 +/- 514) was greater than for UBT-2 (234 +/- 327, p = 0.001). UBT-3 caused only two (10%) FN and three (15%) equivocal results. The 15-min breath sample caused fewer FN and equivocal results than the 10-min sample for both UBT-2 and UBT-3. CONCLUSIONS: Giving citrate before and at the time of 14C-urea administration increases mean breath 14CO2 excretion and decreases FN and equivocal UBT results in patients taking a PPI. These observations suggest that it may be possible to design a UBT protocol that will remain accurate in the face of PPI therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Can endoscopic ultrasound or magnetic resonance cholangiopancreatography replace ERCP in patients with suspected biliary disease? A prospective trial and cost analysis.

OBJECTIVES: ERCP is the gold standard for pancreaticobiliary evaluation but is associated with complications. Less invasive diagnostic alternatives with similar capabilities may be cost-effective, particularly in situations involving low prevalence of disease. The aim of this study was to compare the performance of endoscopic ultrasound (EUS) with magnetic resonance cholangiopancreatography (MRCP) and ERCP in the same patients with suspected extrahepatic biliary disease. The economic outcomes of EUS-, MRCP-, and ERCP-based diagnostic strategies were evaluated. METHODS: Prospective cohort study of patients referred for ERCP with suspected biliary disease. MRCP and EUS were performed within 24 h before ERCP. The investigators were blinded to the results of the alternative imaging studies. A cost-utility analysis was performed for initial ERCP, MRCP, and EUS strategies for these patients. RESULTS: A total of 30 patients were studied. ERCP cholangiogram failed in one patient, and another patient did not complete MRCP because of claustrophobia. The final diagnoses (N = 28) were CBD stone (mean = 4 mm; range = 3-6 mm) in five patients; biliary stricture in three patients, and normal biliary tree in 20. Two patients had pancreatitis after therapeutic ERCP, one after precut sphincterotomy followed by a normal cholangiogram. EUS was more sensitive than MRCP in the detection of choledocolithiasis (80% vs 40%), with similar specificity. MRCP had a poor specificity and positive predictive value for the diagnosis of biliary stricture (76%/25%) compared to EUS (100%/100%), with similar sensitivity. The overall accuracy of MRCP for any abnormality was 61% (95% CI = 0.41-0.78) compared to 89% (CI = 0.72-0.98) for EUS. Among those patients with a normal biliary tree, the proportion correctly identified with each test was 95% for EUS and 65% for MRCP (p < 0.02). The cost for each strategy per patient evaluated was $1346 for ERCP, $1111 for EUS, and $1145 for MRCP. CONCLUSIONS: In this patient population with a low disease prevalence, EUS was superior to MRCP for choledocholithiasis. EUS was most useful for confirming a normal biliary tree and should be considered a low-risk alternative to ERCP. Although MRCP had the lowest procedural reimbursement, the initial EUS strategy had the greatest cost-utility by avoiding unnecessary ERCP examinations.

Adult↗

Accurate diagnosis of Helicobacter pylori. 14C-urea breath test.

The 14C-urea breath test is an accurate means of identifying the presence of H. pylori infection before and after antimicrobial therapy. Several issues, including out of office analysis, the need for a support structure to perform the test, concerns regarding radiation exposure, and inconsistent reimbursement, have slowed the widespread acceptance of the 14C-urea breath test in clinical practice. Despite these problems, the 14C-urea breath test is simple, rapid, and relatively inexpensive compared with the currently available version of the 13C-urea breath test. As such, the 14C-urea breath test provides an attractive, nonendoscopic means of identifying active H. pylori infection.

Breath Tests↗