http://nova.newcastle.edu.au/vital/access/services/Feed ${session.getAttribute("locale")} 5 http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12775 Noncardiac chest pain (NCCP) is very prevalent in the community. Although mortality remains low, morbidity and the financial implications are high. Women, especially those of middle age, should be thoroughly investigated as per current guidelines for coronary artery disease before labeling their chest pain as NCCP. Gastroesophageal reflux disease is the most common cause of NCCP; however other esophageal pathology including esophageal hypersensitivity, neuromuscular disease and eosinophilic esophagitis may also cause NCCP. Proton pump inhibitors are commonly used initially to manage NCCP, although patients who do not respond to this therapy require further investigation and differing treatment regimes. This article will focus on current knowledge regarding GI tract-related NCCP management strategies. 2013-04-16T05:17:12.810Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12781 We evaluated the effect of aerosolized fluticasone therapy on symptomatic dysphagia and histologic eosinophilia in adults with eosinophilic esophagitis (EoE). We performed a double-blind, randomized, placebo-controlled trial of fluticasone in 42 adult patients with a new diagnosis of EoE (30 men; mean age, 37.5 y). Participants were assigned randomly to groups that swallowed 880 μg of aerosolized fluticasone twice daily (n = 21), or took a placebo inhaler twice daily (n = 15) for 6 weeks. End points of the study were symptomatic and histologic response. A complete histologic response (>90% decrease in mean eosinophil count) was observed in 11 of 15 subjects who received 6 weeks of fluticasone (62%), compared with none of the 15 subjects who received placebo (P < .001), based on intention-to-treat analysis; histologic responses were observed in 68% of subjects who received fluticasone (13 of 19) compared with none of those who received placebo (0 of 15) by per-protocol analysis (P < .001). Intracellular staining for eosinophil-derived neurotoxin was reduced in 81% of subjects who received fluticasone (13 of 16) compared with 8% who received placebo (1 of 13) (P < .001). Dysphagia was reduced in 57% of subjects who received fluticasone (12 of 21) compared with 33% who received placebo (7 of 21) (P = .22) by intention-to-treat analysis; dysphagia was reduced in 63% of patients who received fluticasone (12 of 19) and 47% of those who received placebo (7 of 15) (P = .49) based on per-protocol analysis. Esophageal candidiasis developed in 26% of subjects who received fluticasone (5 of 19), but in none of the subjects in the placebo group (P = .05). Aerosolized, swallowed fluticasone leads to a histologic but not a symptomatic response in adults with EoE. 2013-04-16T05:09:47.596Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12780 Esophageal adenocarcinoma (EA) is increasingly common among patients with Barrett's esophagus (BE). We aimed to provide consensus recommendations based on the medical literature that clinicians could use to manage patients with BE and low-grade dysplasia, high-grade dysplasia (HGD), or early-stage EA. We performed an international, multidisciplinary, systematic, evidence-based review of different management strategies for patients with BE and dysplasia or early-stage EA. We used a Delphi process to develop consensus statements. The results of literature searches were screened using a unique, interactive, Web-based data-sifting platform; we used 11,904 papers to inform the choice of statements selected. An a priori threshold of 80% agreement was used to establish consensus for each statement. Eighty-one of the 91 statements achieved consensus despite generally low quality of evidence, including 8 clinical statements: (1) specimens from endoscopic resection are better than biopsies for staging lesions, (2) it is important to carefully map the size of the dysplastic areas, (3) patients that receive ablative or surgical therapy require endoscopic follow-up, (4) high-resolution endoscopy is necessary for accurate diagnosis, (5) endoscopic therapy for HGD is preferred to surveillance, (6) endoscopic therapy for HGD is preferred to surgery, (7) the combination of endoscopic resection and radiofrequency ablation is the most effective therapy, and (8) after endoscopic removal of lesions from patients with HGD, all areas of BE should be ablated. We developed a data-sifting platform and used the Delphi process to create evidence-based consensus statements for the management of patients with BE and early-stage EA. This approach identified important clinical features of the diseases and areas for future studies. 2013-04-16T05:08:44.109Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12779 Background: Limited published data exist on the associated comorbid conditions with functional dyspepsia (FD). Aims: This study aimed to assess the prevalence, services, and costs related to comorbid conditions associated with FD and the risk of having FD for each comorbid condition. Methods: A retrospective database analysis was undertaken using payroll data and adjudicated claims from January 1, 2001, through December 31, 2004 among >300,000 employees. Employees with FD were compared to propensity-score-matched employees without FD (controls). Outcome measures included the prevalence, costs, and utilization of health services for comorbid conditions as defined by the Agency for Healthcare Research and Quality (AHRQ) and the odds ratios of having FD from a multivariate model. Results: FD employees (N = 1,669) and a 50:1 matched control cohort (N = 83,450) were compared. Compared to matched controls, FD employees were more likely to have all major diagnostic categories. Moreover, 199/261 of the AHRQ’s specific categories were more common in the FD cohort. Annual medical costs for the FD cohort were greater than for controls in 155/261 (59%) specific categories and significantly greater (P ≤ 0.05) in 76 categories (29%). Similarly, services were greater for 179/261 (69%) specific categories and significantly greater (P ≤ 0.05) in 110 categories (42%). In a multivariate model, esophageal disorders, gastritis and duodenitis, and abdominal pain were the most associated with having FD (odds ratios 3.8, 3.7, and 3.6, respectively). Only hypertension complications and disorders of the teeth and jaw were significantly negatively associated with FD.Conclusion: There is unexplained excess comorbidity associated with FD which may be a major determining factor for excess healthcare services and costs. 2013-04-16T05:07:52.215Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12778 Background & Aims: The prevalence of chronic constipation (CC) has been reported to be as high as 20% in the general population, but little is known about its natural history. We estimated the natural history of CC and characterized features of persistent CC and nonpersistent CC, compared with individuals without constipation. Methods: In a prospective cohort study, we analyzed data collected from multiple, validated surveys (minimum of 2) of 2853 randomly selected subjects, over a 20-year period (median, 11.6 years). Based on responses, subjects were characterized as having persistent CC, nonpersistent CC, or no constipation. We assessed the association between constipation status and potential risk factors using logistic regression models, adjusting for age and sex. Results: Of the respondents, 84 had persistent CC (3%), 605 had nonpersistent CC (21%), and 2164 had no symptoms of constipation (76%). High scores from the somatic symptom checklist (odds ratio [OR] = 2.1; 95% confidence interval [CI], 1.3–3.4) and frequent doctor visits (OR = 2.0; 95% CI, 1.0–3.8) were significantly associated with persistent CC, compared with subjects with no constipation symptoms. The only factor that differed was increased use of laxatives or fiber among subjects with persistent CC (OR = 3.0; 95% CI, 1.9–4.9). Conclusions: The prevalence of constipation might be exaggerated—the proportion of the population with persistent CC is low (3%). Patients with persistent and nonpersistent CC have similar clinical characteristics, although individuals with persistent CC use more laxatives or fiber. CC therefore appears and disappears among certain patients, but we do not have enough information to identify these individuals in advance. 2013-04-16T05:06:47.349Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12777 Objectives: In patients with diabetes mellitus (DM) and upper gastrointestinal symptoms, a diagnosis of diabetic gastroparesis is often considered, but population-based data on the epidemiology of diabetic gastroparesis are lacking. We aimed to estimate the frequency of and risk factors for gastroparesis among community subjects with DM. Methods: In this population-based, historical cohort study, the medical records linkage system of the Rochester Epidemiology Project was used to identify 227 Olmsted County, MN residents with type 1 DM in 1995, a random sample of 360 residents with type 2 DM, and an age- and sex-stratified random sample of 639 nondiabetic residents. Using defined diagnostic criteria, we estimated the subsequent risk of developing gastroparesis in each group through 2006. The risk in DM, compared with frequency-matched community controls, was assessed by Cox proportional hazards modeling. Results: The cumulative proportions developing gastroparesis over a 10-year time period were 5.2% in type 1 DM, 1.0% in type 2 DM, and 0.2% in controls. The age- and gender-adjusted hazard ratios (HRs) for gastroparesis (relative to controls) was 33 (95% confidence interval (CI): 4.0, 274) in type 1 DM and 7.5 (95% CI: 0.8, 68) in type 2 DM. The risk of gastroparesis in type 1 DM was significantly greater than in type 2 DM (HR: 4.4 (1.1, 17)). Heartburn (HR: 6.6 (1.7, 25)) at baseline was associated with diabetic gastroparesis in type 1 DM. Conclusions: Gastroparesis is relatively uncommon in patients with DM, although an increased risk for gastroparesis was observed in type 1 DM. 2013-04-16T05:05:53.857Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12776 Objective: There are few prospective studies of the prevalence of colonic neoplasia in the normal population. In order to properly evaluate screening-protocols for colorectal cancer in risk groups (e.g., older subjects or those with a family history), it is essential to know the prevalence of adenomas and cancer in the normal population. Methods: A prospective population-based colonoscopy study on 745 individuals born in Sweden aged 19–70 years was conducted (mean age 51.1 years). All polyps seen were retrieved and examined. Results: Out of the 745 individuals 27% had polyps, regardless of kind. Adenomas were found in 10% of the individuals and finding of adenomas was positively correlated to higher age. Men had adenomas in 15% and women in 6% of the cases. Women had a right-sided dominance of adenomas. Hyperplastic polyps were seen in 21% of the individuals. The presence of hyperplastic polyps was significantly positively correlated to the presence of adenomas. Advanced adenomas were seen in 2.8% of the study participants, but no cancers were detected. Conclusion: One in 10 healthy subjects had an adenoma but advanced adenomas were uncommon. Men and women have a different adenoma prevalence and localization. The results provide baseline European data for evaluating colonoscopy screening-protocols for colorectal cancer risk groups, and the findings may have implications for colon cancer screening in the normal, otherwise-healthy population. 2013-04-16T05:04:30.279Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12774 Fecal incontinence is a common condition, which leads to impaired quality of life and huge financial cost at an individual and societal level. Recent studies have identified novel and potentially modifiable risk factors. Newer diagnostic modalities are giving more detailed information about underlying disorders, helping to implement targeted treatment. Many therapeutic options exist, and newer treatments are changing outcomes. This article will review recent developments in mechanisms, diagnosis, and treatment of fecal incontinence. Potentially modifiable risk factors have recently been identified, and should translate to changes in clinical practice and hopefully patient outcomes. These include diarrhea, smoking, and dietary fiber. Advances have been made in anatomical and physiological testing of the anorectum and this may assist in clarifying the diagnosis and guiding management. The long-term benefit of biofeedback has been questioned but patient selection may be key. Novel pharmacological therapies (e.g., clonidine) and minimally invasive surgical procedures are changing outcomes in well selected patients. The development of a magnetic anal sphincter may add a new management alternative in patients who are refractory to conservative management. Fecal incontinence remains a clinical challenge. Only a minority of persons with fecal incontinence seek treatment, but for those who do, improved understanding of risk factors coupled with diagnostic techniques and treatments are improving outcomes. 2013-04-16T05:02:43.590Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12773 The current health-care environment is demanding evidence-based medicine that relies on clinical trials as the basis for decisions. Clinician investigators are more often finding that they are personally responsible for coordinating large, multisite trials. We present strategies for successful implementation and management of multisite clinical trials and knowledge gained through an international, multisite randomized clinical trial. Topics include team composition, regulatory requirements, study organization and governance, communication strategies, recruitment and retention efforts, budget, technology transfer, and publication. 2013-04-16T05:01:48.613Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12771 Background: Quality of life is impaired in some people with IBS, but the level of symptoms that may drive this impairment is unclear. Aims: We aimed to identify whether current frequency and severity cut-offs for IBS-type symptoms are associated with a clinically meaningful impairment of quality of life in the community. Methods: People who met modified Rome III criteria for IBS (n = 201) and controls (n = 1,904) were assessed. Frequency of IBS symptoms was grouped a priori into ‘less frequent’ (not at all and sometimes) and ‘more’ frequent (often, very often and almost always). Severity of abdominal pain was grouped into ‘mild’ (very mild and mild) and severe (moderate, severe and very severe). Mental and physical functioning was measured using the valid SF-12, with ‘normal’ functioning (defined as a score of >43 and >48) and ‘impaired’ functioning (defined as a score of ≤43 and ≤48), respectively. Psychological variables were assessed via valid self-report. Results: Having ‘more’ versus ‘less’ severe abdominal pain (OR = 9.41; 95% CI 1.17–75.43, P = 0.03) and ‘more’ versus ‘less’ frequent diarrhoea (OR = 2.19; 95% CI 1.13–4.26, P = 0.02) along with increasing age (OR = 1.03; 95% CI 1.01–1.05, P = 0.003) were significant independent predictors of having impairment in physical functioning. In terms of psychological factors, having higher levels of depression (OR = 1.61; 95% CI 1.36–1.91) and somatic distress (OR = 1.17; 95% CI 1.09–1.27) were independently associated with mental and physical impairment, respectively. Conclusion: The current frequency and severity threshold cut-offs for IBS symptoms in the Rome III criteria are associated with a clinically meaningful impairment of quality of life in community subjects with IBS. 2013-04-16T04:59:44.628Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12769 Background & Aims: The rapid response to topical corticosteroids makes it hard to implicate fibrosis as the cause of dysphagia in patients with eosinophilic esophagitis (EoE). We examined surrogates of esophageal expansion using minimal and maximal esophageal diameter (EDmin and EDmax) in barium swallow examinations. Methods: Eleven patients evaluated at Mayo Clinic, Rochester (8 female, median age 40, median diagnosis 36 months, median symptom duration 132 months) underwent barium esophagrams to determine EDmin and EDmax before and after 6 weeks of topical corticosteroid therapy. We assessed parameter reproducibility (in healthy volunteers), baseline EDmin and EDmax, postcorticosteroid changes in EoE patients, and correlation with clinical response. Results: EDmin and EDmax were reproducible, with nonsignificant variance in the 2 esophagrams in control subjects (P = .44 and P = .66, respectively). Baseline EDmax was reduced in EoE at 19 mm (range, 13–26 mm) vs 24 mm (range, 19–29 mm) in controls (P = .004). About 50% of the EoE patients had EDmax and min values within the 10th to 90th percentile of controls (45% and 55%, respectively). Clinical improvement by Mayo Dsyphagia Questionnaire did not correlate with postcorticosteroid luminal change (P = .19 for EDmax; P = .75 for EDmin). Median increases in postcorticosteroid EDmax and EDmin were not statistically significant (P = .15 and .1, respectively). However, they were significant in patients with abnormal baseline EDmax (n = 6; 2 mm; P = .01) and EDmin (n = 5; 3 mm; P = .02). Conclusions: Esophageal diameter is a reproducible parameter that is frequently decreased in EoE, but normal in approximately 50% of patients. Those with narrowing might respond to steroids, but it is unclear if narrowing causes dysphagia. 2013-04-16T04:57:31.465Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12768 Objective: To assess the incidence and mortality impact of upper and lower gastrointestinal (GI) events in rheumatoid arthritis (RA) compared to non-RA subjects. Methods: We identified incident upper and lower GI events and estimated their incidence rates using person-year methods in a population-based incident RA cohort of residents of Olmsted County, Minnesota, USA (1987 American College of Rheumatology criteria first fulfilled between January 1, 1980, and January 1, 2008) and non-RA subjects from the same population. Results: The study included 813 patients with RA and 813 non-RA subjects (mean followup 10.3 and 10.8 yrs, respectively); 68% women; mean age 55.9 yrs in both cohorts. The rate of upper GI events/100 person-years was 2.9 in RA versus 1.7 in the non-RA cohort (rate ratio 1.7, 95% CI 1.4, 2.2); for lower GI events, the rates were 2.1 in RA versus 1.4 in the non-RA cohort (rate ratio 1.5, 95% CI 1.1, 1.9). The incidence of upper GI bleed, perforation, ulcer, obstruction, and any upper GI event in RA declined over calendar time; the incidence of lower GI events remained unchanged. Exposure to glucocorticoids, prior upper GI disease, abdominal surgery, and smoking were associated with lower GI events in RA. Both upper and lower GI events were associated with increased mortality risk in RA. Conclusion: There is increased risk of serious upper and lower GI events in RA compared to non-RA subjects, and increased GI-related mortality in RA. Prominent declines in incidence of upper, but not lower GI events in RA highlight the need for studies investigating lower GI disease in patients with RA. 2013-04-16T04:56:24.299Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12767 Background: Smaller studies have evaluated SLC6A4 5-HTTLPR and GNβ3 825C>T polymorphisms in IBS, and interactions between 5-HTT LPR with life events have been reported in the psychiatric literature, but gene–environment studies in IBS are lacking. Aims: The purpose of this study was to assess the association of two polymorphisms with IBS and age of onset, and whether there are gene–environment interactions with IBS. Methods: Outpatients with IBS and controls completed a validated questionnaire and provided blood for DNA. Comparisons of genotype/allele frequencies between cases and controls were performed with logistic regression. Linear regression was used to evaluate the association between the variants and age of onset. Environmental variables tested included abuse, parental alcohol abuse, parental psychiatric disorders, and gastrointestinal infections. Results: Genotyping was performed in 385 cases and 262 controls with median age of 50 years (range, 18.0–70.0) and 498 (77 %) females. The IBS subtype distribution among cases was: 102 (26 %) D-IBS, 40 (10 %) C-IBS, 125 (32 %) M-IBS, 118 (31 %) other. No association was observed between IBS or age of onset and both variants. Significant interactions were observed between GI infection and the GNβ3 825T allele. For those reporting gastrointestinal infection, the OR for IBS was 3.9 (95 % CI 1.2–12.7) whereas the OR was 0.86 (95 % CI 0.65–1.13) for those without prior infection. Conclusions: There was a significant interaction between the GNβ3 polymorphism and infection in the development of IBS, suggesting that its etiology is the result of a combination of specific genetic and environmental risk factors. 2013-04-16T04:55:28.147Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12766 Case series have suggested an association between eosinophilic esophagitis (EoE) and celiac disease (CD) in children. We analyzed a cohort of patients with CD to confirm this association in children, and determine whether it extends into adulthood. A database of patients with CD was reviewed to determine the number of patients with comorbid diagnoses of EoE. Histopathology reports of esophageal biopsies were reviewed to identify all cases of increased esophageal eosinophilia. Cases of EoE were diagnosed if biopsies revealed >=15 eosinophils per high power field and associated symptoms were present. Age-adjusted and sex-adjusted standardized incidence ratios (SIR) with corresponding 95% confidence intervals (CI) were calculated in comparison to published US population-derived incidence data. EoE was diagnosed in 4 children and 10 adults. EoE is more common compared with the general population; SIR for children was 35.6 (95% CI, 9.3-79.0) and for adults 13.1 (95% CI, 6.2-22.5). Overall, the age-adjusted and sex-adjusted SIR was 16.0 (95% CI, 8.7-25.5). The incidence of EoE in our cohort of patients with CD was increased compared with the general population. Coexistent EoE should be considered in patients with CD who have persistent esophageal symptoms. 2013-04-16T04:54:28.043Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12765 Gastroparesis (GP) is characterized by delayed gastric emptying in the absence of mechanical outlet obstruction. Symptoms may include nausea, vomiting, bloating, early satiety, abdominal pain, and weight loss. Delayed gastric emptying of a solid-phase meal assessed by radionuclear scintigraphy is the criterion standard for diagnosis. The prevalence of GP is difficult to estimate due to the lack of a validated, widely available diagnostic test that can be applied in primary care. The extent of this problem in children is unknown. We studied a cohort of children with GP diagnosed by radionuclear scintigraphy to identify demographics, symptoms, comorbidities, treatment, and outcomes. A retrospective analysis of 239 patients between ages 0 and 21 years was performed. The mean age of presentation was 7.9 years, and boys and girls were almost equally affected, that is, 48.5% and 51.5%, respectively. Vomiting was the most frequent presenting symptom (68%), followed by abdominal pain (51%), nausea (28%), weight loss (27%), early satiety (25%), and bloating (7%). Almost 75% of patients responded to intravenous erythromycin administered provocatively during gastric scintigraphy. In a majority of the patients, no cause was identified, that is, idiopathic GP (70%), followed by drugs (18%) and postsurgical (12.5%) causes. Only 4% patients had diabetic GP, and our population was essentially narcotic naive (2%). After an average of 24 months' follow-up, the most common complication was esophageal reflux (67%). Despite different therapeutic modalities, by the end of the follow-up period, a significant improvement in symptoms was reported by an average of 60%, regardless of sex, age, or degree of emptying delay. GP has a good prognosis in childhood despite different etiologies, symptom presentation, and therapy. 2013-04-16T04:53:27.762Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12764 Functional dyspepsia (FD) is a common problem affecting up to 10–25% of individuals. FD accounts for significant health care costs and affects quality of life but has no definitive treatment. The Functional Dyspepsia Treatment Trial (FDTT) aims to test whether treatment with an antidepressant (amitriptyline or escitalopram) leads to improvement of symptoms in patients with moderate to severe FD. The FDTT is an international multicenter, parallel group, randomized, double-blind, placebo-controlled trial to evaluate whether 12 weeks of treatment with escitalopram or amitriptyline improves FD symptoms compared to treatment with placebo. Secondly, it is hypothesized that acceleration of solid gastric emptying, reduction of postprandial satiation, and enhanced gastric volume change with a meal will be significant positive predictors of short- and long-term outcomes for those on antidepressants vs. placebo. The third aim is to examine whether polymorphisms of GNβ3 and serotonin reuptake transporter influence treatment outcomes in FD patients receiving a tricyclic antidepressant, selective serotonin reuptake inhibitor therapy, or placebo. The FDTT enrollment began in 2006 and is scheduled to randomize 400 patients by the end of 2012 to receive an antidepressant or placebo for 12 weeks, with a 6-month post-treatment follow-up. The study incorporates multiple validated questionnaires, physiological testing, and specific genetic evaluations. The protocol was approved by participating centers' Institutional Review Boards and an independent Data Safety Monitoring Board was established for monitoring to ensure patient safety and a single interim review of the data in December 2010 (ClinicalTrials.gov number NCT00248651). 2013-04-16T04:52:31.853Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12371 Aim: To determine whether distinct symptom groupings exist in a constipated population and whether such grouping might correlate with quantifiable pathophysiological measures of colonic dysfunction. Methods: One hundred and ninety-one patients presenting to a Gastroenterology clinic with constipation and 32 constipated patients responding to a newspaper advertisement completed a 53-item, wide-ranging self-report questionnaire. One hundred of these patients had colonic transit measured scintigraphically. Factor analysis determined whether constipation-related symptoms grouped into distinct aspects of symptomatology. Cluster analysis was used to determine whether individual patients naturally group into distinct subtypes. Results: Cluster analysis yielded a 4 cluster solution with the presence or absence of pain and laxative unresponsiveness providing the main descriptors. Amongst all clusters there was a considerable proportion of patients with demonstrable delayed colon transit, irritable bowel syndrome positive criteria and regular stool frequency. The majority of patients with these characteristics also reported regular laxative use. Conclusion: Factor analysis identified four constipation subgroups, based on severity and laxative unresponsiveness, in a constipated population. However, clear stratification into clinically identifiable groups remains imprecise. 2013-03-06T22:50:11.528Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12435 Objective: A single previous paper on this topic found a direct pathway between cognitive behavioral therapy (CBT) and an irritable bowel syndrome (IBS) global symptom score. This is controversial since under the biopsychosocial model, the expectation is that CBT's effect would be mediated by mood. Using more sensitive bowel symptom scales and measurements at additional time points, we aimed to compare the relative strengths of direct pathways between CBT and change in IBS symptoms and indirect pathways that operate via mood state using structural equation modeling. Methods: Our data set included 105 people with Rome I IBS randomized to individual CBT (n=34), relaxation therapy (n=36), and usual medical care (n=35). The primary outcome was defined as adequate relief of IBS symptoms in terms of the distress, frequency, and impairment according to the Bowel Symptom Severity Scale. Outcomes in functional status (according to the 36-item Short-Form Health Survey) and psychological status (Hospital Anxiety and Depression Scale) were secondary outcomes. Results: Our data suggest indirect pathways that operate via mood, most clearly anxiety but to a lesser extent depression. Statistically significant pathways were identified that lead from CBT to change in mood state thence to change in bowel symptoms, followed by further changes in mood then changes in bowel symptoms. Our data provide no evidence of direct effect of CBT on bowel symptoms. Conclusions: The present study suggests that CBT may operate via changes in mood state while not ruling out the possibility of direct effects. Our findings do not directly support, but are consistent with, a biopsychosocial model. 2013-01-16T00:50:03.978Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12436 Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of the gastrointestinal tract. Collectively they are termed inflammatory bowel disease (IBD) and it is estimated that 1.5 million Americans suffer from UC and CD. Their etiologies are unknown, although both are thought to arise from a disordered immune response to the gut contents in genetically predisposed individuals. The characteristics of the inflammatory response are different, with CD typically causing transmural inflammation and occasionally associated with granulomas, whereas in UC the inflammation is usually confined to the mucosa. Both UC and CD exhibit a relapsing and remitting course and there is a significant, often dramatic, reduction in quality of life during exacerbations of the disease. This has an impact on psychological health, with active IBD patients experiencing greater levels of distress and feelings of lack of sense of self-control compared with the normal population and patients with inactive IBD. Extrapolation from US administrative claims databases suggests that IBD is responsible for 2.3 million physician visits, 180,000 hospital admissions, and costs $6.3 billion annually. There have been recent guidelines on the management of both UC and CD that direct the clinician on diagnosis and treatment. Approximately 33% of the cost of IBD is due to medical therapy, and given the substantial clinical burden and economic cost of IBD it is important to establish the effectiveness of current medical therapies in both UC and CD. Although there have been several systematic reviews on the efficacy of therapy, this is a rapidly changing field and there is a need for a comprehensive review of the literature. The American College of Gastroenterology IBD Task Force developed a protocol for systematically reviewing the data on currently available therapies for UC and CD, both in inducing remission and in preventing relapse of the disease. Evidence-based statements were then developed and the strength of recommendation for each was graded according to standard criteria. 2013-01-16T00:50:03.767Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12433 Background: Eosinophilic esophagitis (EoE) is defined by a minimum of 15 eosinophils (eos) per high-powered field (HPF) on esophageal biopsy, along with esophageal symptoms and the exclusion of gastroesophageal reflux (GERD). The clinical significance of fewer eosinophils is unknown. Methods: Fifty-nine adult patients without a previous diagnosis of EoE with esophageal biopsies containing 1–14 eos per HPF (low grade eosinophilia) and 418 adult patients with ≥15 eos per HPF were identified by retrospective review. Patients were divided into group A (1–9 eos per HPF), group B (10–14 eos per HPF), and group C (≥15 eos per HPF) with a chart review of clinical and demographic data. Results: While dysphagia and atopy (asthma and allergic rhinitis) were more common in patients with ≥15 eos per HPF (group C) than those with low grade esophageal eosinophilia (groups A and B) (93 vs. 88%, P = 0.02), food impaction and heartburn occurred at an equal frequency across all patient groups. Endoscopic findings were likewise similar between groups. Of the 14 patients with low grade esophageal eosinophilia who underwent repeat endoscopy a mean interval of 42 weeks (range 8–118 weeks) later, five (36%) met conventional diagnostic criteria for EoE of 15 or greater eos per HPF. Follow-up in ten patients treated with topical corticosteroids noted improvement in nine, with mean follow-up of 8 weeks (range 4–12 weeks). Conclusion: Some adult patients with dysphagia and less than 15 eos per HPF have similar endoscopic findings and clinical course to patients meeting the consensus definition of EoE. Further evaluation of patients with low grade esophageal eosinophilia is needed. 2013-01-16T00:30:05.926Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12432 Objectives: Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract. Evidence for treatment with 5-aminosalicylic acid (5-ASA) drugs is conflicting. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine this issue. Methods: MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through December 2010). Authors of studies were contacted to provide additional information on trials where required, and experts in the field were contacted to identify unpublished studies. Eligible trials recruited adults with active or quiescent CD and compared 5-ASAs with placebo, or no treatment. Dichotomous data were pooled to obtain relative risk (RR) of failure to achieve remission in active CD, and RR of relapse of disease activity in quiescent CD, with a 95% confidence interval (CI). The number needed to treat (NNT) was calculated from the reciprocal of the risk difference. Results: The search identified 3,061 citations. Twenty-two RCTs were eligible. Six RCTs compared 5-ASA with placebo in active CD remission. There was a trend towards a benefit with sulfasalazine over placebo (two RCTs, RR of failure to achieve remission=0.83; 95% CI=0.69–1.00), but no definite benefit of mesalamine over placebo (four RCTs, RR=0.91; 95% CI=0.77–1.06). Neither sulfasalazine nor mesalamine were effective in preventing quiescent CD relapse, but in a per protocol analysis mesalamine appeared to reduce risk of relapse (RR=0.79; 95% CI=0.66–0.95, NNT=13). Conclusions: The role of 5-ASAs in inducing remission of active CD and preventing relapse of quiescent CD remains uncertain, and more RCTs are required. 2013-01-16T00:30:05.904Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12431 Objectives: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory disorders of the gastrointestinal tract of unknown etiology. Evidence for treatment of the condition with biological therapies exists, but no systematic review and meta-analysis has examined this issue in its entirety. Methods: MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through to December 2010). Trials recruiting adults with active or quiescent CD or UC and comparing biological therapies (anti-tumor necrosis factor-α (TNFα) antibodies or natalizumab) with placebo were eligible. Dichotomous symptom data were pooled to obtain relative risk (RR) of failure to achieve remission in active disease and RR of relapse of activity in quiescent disease once remission had occurred, with a 95% confidence interval (CI). Results: The search strategy identified 3,061 citations, 27 of which were eligible. Anti-TNFα antibodies and natalizumab were both superior to placebo in inducing remission of luminal CD (RR of no remission=0.87; 95% CI 0.80–0.94 and RR=0.88; 95% CI 0.83–0.94, respectively). Anti-TNFα antibodies were also superior to placebo in preventing relapse of luminal CD (RR of relapse=0.71; 95% CI 0.65–0.76). Infliximab was superior to placebo in inducing remission of moderate to severely active UC (RR=0.72; 95% CI 0.57–0.91). Conclusions: Biological therapies were superior to placebo in inducing remission of active CD and UC, and in preventing relapse of quiescent CD. 2013-01-16T00:20:04.015Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12403 Objectives: There remains controversy regarding the efficacy of thiopurine analogs (azathioprine (AZA) and 6-mercaptopurine (6-MP)), methotrexate (MTX), and cyclosporine for the treatment of inflammatory bowel disease (IBD). We performed an updated systematic review of the literature to clarify the efficacy of immunosuppressive therapy at inducing remission and preventing relapse in ulcerative colitis (UC) and Crohn's disease (CD). Methods: Only parallel group randomized controlled trials (RCTs) were considered eligible. Studies with adult IBD patients receiving immunosuppressive therapy compared with placebo for at least 14 days and up to 17 weeks for active disease, or at least 6 months in quiescent disease were analyzed. Two reviewers independently assessed eligibility and extracted data. The primary outcome was remission or relapse using an intention-to-treat analysis. The data were summarized using relative risk (RR) and pooled using a random effects model. Results: Data on MTX and cyclosporine in IBD were limited although there were some data to support the use of intramuscular MTX in CD but not UC. There were five trials of AZA/6-MP in 380 active CD patients and there was no significant effect of therapy inducing remission (RR=0.87; 95% confidence interval (CI)=0.71–1.06). In quiescent CD, there were two trials involving 198 patients with no significant benefit of active therapy preventing relapse compared with placebo (RR=0.64; 95% CI=0.34–1.23). There were, however, three additional AZA withdrawal trials in 163 patients that indicated continuing medication did prevent relapse (RR=0.39; 95% CI=0.21–0.74). There were two AZA RCTs in 130 active UC patients that suggested a trend for benefit of therapy, but this did not reach statistical significance (RR=0.85; 95% CI=0.71–1.01). In quiescent UC, there were three trials involving 127 patients and there was a statistically significant benefit of AZA preventing relapse (RR=0.60; 95% CI=0.37–0.95). Conclusions: Most evidence relates to AZA/6-MP where there is no statistically significant benefit at inducing remission in active CD and UC. Thiopurine analogs may prevent relapse in quiescent UC and CD. However, there is a paucity of data for immunosuppressive therapy in IBD and more research is needed. 2013-01-11T05:30:04.618Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12402 Objectives: The use of glucocorticosteroids to treat both Crohn's disease (CD) and ulcerative colitis (UC) is widespread, but no systematic review and meta-analysis has examined the issue of efficacy of these agents in its entirety. Methods: MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through December 2010). Randomized controlled trials (RCTs) recruiting adults with active or quiescent CD comparing standard glucocorticosteroids or budesonide with placebo or each other, or comparing standard glucocorticosteroids with placebo in active UC, were eligible. Dichotomous data were extracted to obtain relative risk (RR) of failure to achieve remission in active disease, and RR of relapse of activity in quiescent disease, with a 95% confidence interval (CI). Adverse events data were extracted where reported. Results: The search identified 3,061 citations, and 20 trials were eligible. Only one trial was at low risk of bias. Standard glucocorticosteroids were superior to placebo for UC remission (RR of no remission=0.65; 95% CI 0.45–0.93). Both trials of standard glucocorticosteroids in CD remission reported a statistically significant effect, but because of heterogeneity between studies, the overall effect was not significant (RR=0.46; 95% CI 0.17–1.28). Budesonide was superior to placebo for CD remission (RR=0.73; 95% CI 0.63–0.84), but not in preventing CD relapse (RR=0.93; 95% CI 0.83–1.04). Standard glucocorticosteroids were superior to budesonide for CD remission (RR=0.82; 95% CI 0.68–0.98), but glucocorticosteroid-related adverse events were commoner (RR=1.64; 95% CI 1.34–2.00). Conclusions: Standard glucocorticosteroids are probably effective in inducing remission in UC, and may be of benefit in CD. Budesonide induces remission in active CD, but is less effective than standard glucocorticosteroids, and is of no benefit in preventing CD relapse. 2013-01-11T01:10:04.886Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12400 The etiology of inflammatory bowel disease (IBD) is unknown but may relate to an unidentified bacterial pathogen or an immunological reaction to gut microbiota. Antibiotics have therefore been proposed as a therapy for Crohn's disease (CD) and ulcerative colitis (UC) to induce remission in active disease to prevent relapse. Current data are conflicting and we therefore conducted a systematic review of randomized controlled trials (RCTs) evaluating antibiotics in IBD. Only parallel group RCTs were considered eligible. Studies with adult patients receiving any dose of therapy for at least 7 days and up to 16 weeks for active disease, or at least 6 months of follow-up for preventing relapse in quiescent disease were analyzed. We included any antibiotics alone or in combination using predefined definitions of remission and relapse. Two reviewers independently assessed eligibility and extracted data. The primary outcome was remission or relapse using an intention-to-treat methodology. The data were summarized using relative risk (RR) and pooled using a random effects model. For active CD, there were 10 RCTs involving 1,160 patients. There was a statistically significant effect of antibiotics being superior to placebo (RR of active CD not in remission=0.85; 95% confidence interval (CI)=0.73–0.99, P=0.03). There was moderate heterogeneity between results (I²=48%) and a diverse number of antibiotics were tested (anti-tuberculosis therapy, macrolides, fluroquinolones, 5-nitroimidazoles, and rifaximin) either alone or in combination. Rifamycin derivatives either alone or in combination with other antibiotics appeared to have a significant effect at inducing remission in active CD. In perianal CD fistula there were three trials evaluating 123 patients using either ciprofloxacin or metronidazole. There was a statistically significant effect in reducing fistula drainage (RR=0.8; 95% CI=0.66–0.98) with no heterogeneity (I²=0%) and an number needed to treat 5 (95% CI=3–20). For quiescent CD, there were 3 RCTs involving 186 patients treated with different antibiotics combinations (all including antimycobacterials) vs. placebo. There was a statistically significant effect in favor of antibiotics vs. placebo (RR of relapse=0.62; 95% CI=0.46–0.84), with no heterogeneity (I²=0%). In active UC, there were 9 RCTs with 662 patients and there was a statistically significant benefit for antibiotics inducing remission (RR of UC not in remission=0.64; 95% CI=0.43–0.96). There was moderate heterogeneity (I²=69%) and antibiotics used were all different single or combination drugs. Antibiotic therapy may induce remission in active CD and UC, although the diverse number of antibiotics tested means the data are difficult to interpret. This systematic review is a mandate for further trials of antibiotic therapy in IBD. 2013-01-11T00:00:05.523Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12399 Objectives: Immune activation may have an important pathogenic role in the irritable bowel syndrome (IBS). While little is known about immunologic function in functional dyspepsia (FD), we have observed an association between cytokine secretion by peripheral blood mononuclear cells (PBMCs) and symptoms in IBS. Upper gastrointestinal inflammatory diseases are characterized by enhanced small bowel homing α4-, β7-integrin, chemokine receptor 9 (CCR9) positive T lymphocytes. We hypothesized that increased cytokine release and elevated circulating small bowel homing T cells are linked to the severity of symptoms in patients with FD. Thus, we aimed to (i) compare cytokine release in FD and healthy controls (HCs), (ii) quantify “gut homing” T cells in FD compared with HC and patients with IBS, and (iii) correlate the findings to symptom severity and gastric emptying. Methods: PBMC from 45 (Helicobacter pylori negative) patients with FD (Rome II) and 35 matched HC were isolated by density gradient centrifugation and cultured for 24h. Cytokine production (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-10) was measured by enzyme-linked immunosorbent assay. CD4+ α4β7+CCR9+ T cells were quantified by flow cytometry in FD, HC and 23 patients with IBS. Gastric emptying was measured by scintigraphy. Symptom severity was assessed utilizing the standardized Gastrointestinal Symptom Score. Results: FD patients had significantly higher TNF-α (107.2±42.8 vs. 58.7±7.4pg/ml), IL-1β (204.8±71.5 vs. 80.2±17.4pg/ml), and IL-10 (218±63.3 vs. 110.9±18.5pg/ml) levels compared with HC, and enhanced gut homing lymphocytes compared with HC or IBS. Cytokine release and CD4+α4β7+CCR9+ lymphocytes were correlated with the symptom intensity of pain, cramps, nausea, and vomiting. Delayed gastric emptying was significantly associated (r=0.78, P=0.021) with CD4+α4β7+CCR9+ lymphocytes and IL-1β, TNF-α, and IL-10 secretion. Conclusions: Cellular immune activation with increased small bowel homing T cells may be key factors in the clinical manifestations of H. pylori-negative FD. 2013-01-11T00:00:05.018Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12398 Objectives: Population-based data on the epidemiology and outcomes of subjects with intestinal metaplasia of the gastroesophageal junction (IMGEJ) and Barrett's esophagus (BE) are limited. The objectives of this study were to (i) estimate the incidence of IMGEJ and BE diagnosed from clinically indicated endoscopy in Olmsted County, MN, over three decades (1976–2006) and prevalence as of 1 January 2007, (ii) compare baseline characteristics of subjects with IMGEJ and BE, and (iii) study the natural history and survival of both cohorts. Methods: This was a population-based cohort study. The study setting was Olmsted County, MN. Patients with BE (columnar segment >1cm with intestinal metaplasia) and IMGEJ (intestinal metaplasia in biopsies from the gastroesophageal junction) from 1976 to 2006 in Olmsted County, MN, were identified using Rochester Epidemiology Project resources. Demographic and clinical data were abstracted from medical records and pathology confirmed by gastrointestinal pathologists. The association of baseline characteristics with overall and progression-free survival was assessed using proportional hazards regression models. Outcome measures were baseline characteristics and overall survival of subjects with IMGEJ compared to those with BE. Results: In all, 487 patients (401 with BE and 86 with IMGEJ) were identified and followed for a median interval of 7 (BE subjects) to 8 (IMGEJ subjects) years. Subjects with BE were older, heavier, reported reflux symptoms more often, and had higher prevalence of advanced neoplasia than those with IMGEJ. No patient with IMGEJ progressed to esophageal adenocarcinoma (EAC) in contrast to BE subjects who had a cumulative risk of progression of 7% at 10 years and increased risk of death from EAC (standardized mortality ratio 9.62). The overall survival of subjects with BE and IMGEJ did not differ from that expected in similar age- and sex-distributed white Minnesota populations. Conclusions: Subjects with IMGEJ appear to have distinct clinical characteristics and substantially lower cancer progression risk compared to those with BE. 2013-01-10T23:00:03.937Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12396 Diverticular disease and its complications overlap with both irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Diverticular disease and IBS are common gastrointestinal disorders and share common pathophysiologic factors including visceral hypersensitivity, gastrointestinal motor disturbance, a fiber-depleted diet, and subtle mucosal inflammation. New onset IBS-like symptoms in older patients warrant further investigation including colonoscopy to exclude organic diseases. It can be difficult to differentiate symptomatic diverticular disease from IBS, and fecal calprotectin may help in such cases. Rifaximin treatment improves symptoms of both IBS and diverticular disease. The pathogenesis of diverticulitis and diverticular colitis (or known as segmental colitis associated with diverticular disease) may overlap with that of IBD. Pathologic features of IBD can be observed in both diverticulitis and diverticular colitis. Diverticulitis mimics Crohn’s disease in presentation and radiologic findings. A follow-up colonoscopy helps to differentiate diverticulitis from Crohn’s disease. Diverticular colitis is an infrequent complication of diverticular disease and is limited to the segment of colon with diverticula. Patients with diverticular colitis usually respond to mesalamine and have a better prognosis than IBD. Further understanding of the overlap of IBS, IBD, and diverticular disease may shed light into new therapeutic interventions. 2013-01-10T22:30:03.743Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12395 Objectives: Evidence from randomized controlled trials (RCTs) for the use of 5-aminosalicylic acid (5-ASA) drugs in Crohn's disease (CD) in remission after a surgical resection is conflicting. We conducted a systematic review and meta-analysis of RCTs to examine this issue. Methods: MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through April 2010). Eligible trials recruited adults with luminal CD in remission after a surgical resection and compared 5-ASAs with placebo, or no treatment. Dichotomous data were pooled to obtain relative risk (RR) of relapse of disease activity, with a 95% confidence interval (CI). The number needed to treat (NNT) was calculated from the reciprocal of the risk difference. Results: The search strategy identified 3,061 citations. Eleven RCTs were eligible for inclusion containing 1,282 patients. The RR of relapse of CD in remission after surgery with 5-ASA vs. placebo or no therapy was 0.86 (95% CI=0.74–0.99) (NNT=13). Sulfasalazine was of no benefit in preventing relapse in 448 patients (RR=0.97; 95% CI=0.72–1.31), but mesalamine was more effective than placebo or no therapy (RR=0.80; 95% CI=0.70–0.92) in 834 patients, with an NNT of 10. Conclusions: Mesalamine is of modest benefit in preventing relapse of CD in remission after surgery. Its use should be considered in those in whom immunosuppressive therapy is either not warranted or contraindicated. 2013-01-10T22:10:06.019Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12379 Background  Patients with dyspepsia often experience troublesome symptoms. Aim: To assess the burden of uninvestigated dyspepsia (symptoms, health-related quality of life [HRQL] and work productivity) before and after 8 weeks’ esomeprazole treatment. Methods: Patients (n = 1250) with uninvestigated dyspepsia (no endoscopy within 6 months and ≤2 endoscopies within 10 years) underwent a 1-week esomeprazole acid-suppression test before randomisation to 7 weeks’ esomeprazole or placebo. The Reflux Disease Questionnaire (RDQ), Quality of Life in Reflux and Dyspepsia (QOLRAD) and Work Productivity and Activity Impairment (WPAI) questionnaires were completed at baseline (1-week off-treatment) and 8 weeks. WPAI results were further analysed among patients who responded to the acid-suppression test. Results: The highest baseline symptom score was for the RDQ dyspepsia domain, and the highest disease burden was for QOLRAD vitality and food/drink problems. After 8 weeks, significant improvements vs. placebo were observed for all RDQ and QOLRAD domains. The sub-population of acid-suppression test responders, but not the total WPAI population, had a significant work productivity improvement vs. placebo. Conclusions: Uninvestigated dyspepsia is associated with high symptom load and impacts on HRQL and work productivity. Esomeprazole improves HRQL among such patients, and improves work productivity among 1-week acid-suppression trial responders. 2013-01-10T02:01:16.474Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12384 Objectives: Symptomatic gastroesophageal reflux disease (GERD) is associated with a significantly increased risk of esophageal adenocarcinoma, but its natural history in the general population is poorly understood. Whether nonerosive reflux disease (NERD) is a risk factor for Barrett's esophagus (BE), the precursor of esophageal adenocarcinoma, is unknown. Furthermore, quantifying the risk of incident BE in those with untreated reflux esophagitis has not been possible. We aimed, in a prospective follow-up study with endoscopy, to evaluate the risk of BE in a cohort from the Swedish general population (the Kalixanda Study). Methods: Those with endoscopic or histological findings suggestive of GERD and randomly half of those with NERD (n=481) were invited for follow-up investigation including endoscopy and a validated symptom questionnaire 5 years after the initial study. Multinomial logistic regression was used to estimate relative risk ratios (RRRs) and 95% confidence intervals (CIs) for change in presentation of GERD. Results: Of the 405 subjects available for inclusion, endoscopy was performed in 284 (response rate 70.1%). The incidence of BE was 9.9/1,000 person-years. Of those with NERD at baseline (n=113), progression to erosive esophagitis was found in 11; 2 developed BE. Erosive esophagitis (n=90) progressed to a more severe grade in 12 and to BE in 8 cases. Erosive esophagitis at baseline was independently associated with BE at follow-up (RRR 5.2; 95% CI 1.2–22.9). Conclusions: Compared with being free of GERD at follow-up, erosive esophagitis is a major risk factor for BE (with a fivefold increased risk) after 5 years in the general population. 2013-01-10T02:00:03.795Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12383 Introduction: Diagnostic criteria for irritable bowel syndrome (IBS) have not been validated by prospective symptom diary. We investigated the bowel patterns in community subjects with and without non-organic abdominal pain, and compared the symptoms with subjects fulfilling the Rome II criteria (IBS). Methods: From the Swedish population register, a random sample completed an abdominal symptom questionnaire. Responders were subsequently invited for a clinical evaluation and offered a colonoscopy regardless of whether they had abdominal symptoms or not. A total of 268 subjects underwent colonoscopy, clinical evaluation by gastroenterologist, laboratory investigations, and completed the Rome questionnaire and prospective gastrointestinal (GI) symptom diaries for 1 week. Twenty-three subjects of 268 were excluded due to organic GI disease. Results: Subjects recorded 2,194 bowel movements and 370 abdominal pain episodes on 1,504 days. Subjects with pain in the diary (n = 81) had higher stool frequency (P = 0.01), more urgency (P = 0.0002), feelings of incomplete evacuation (P = 0.0002), nausea (P = 0.0009), and abdominal bloating (P = 0.0005) than subjects without pain (n = 151). Twenty-eight subjects (12%) fulfilled the Rome II criteria for IBS. Together, they had 96 pain episodes but only 4% were improved by defecation; 29% of the pain episodes started or worsened after a meal. Subjects with IBS and other subjects with non-organic abdominal pain (n = 64) exhibited no differences in terms of the proportions of pain episodes improved by defecation, bloating, stool frequency, consistency, or defecatory symptoms. Conclusions: Current criteria for IBS that rely on recall of the relationship between abdominal pain and bowel disturbance may overcall this association when measured prospectively. 2013-01-10T01:50:04.109Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12382 Functional gastrointestinal disorders (FGIDs) are common and currently defined by a symptom-based classification with no discernable pathology. In functional dyspepsia (FD), the duodenum is now implicated as a key area where symptoms originate. This is attributed to immune activation with increasing evidence indicating a role for duodenal eosinophilia. In irritable bowel syndrome (IBS), mastocytosis has been documented throughout the small and large intestine. Eosinophils and mast cells are an important link between innate and adaptive immunity, and are important in allergic type TH2 inflammation. Eosinophils may give rise to symptoms due to release of preformed cytokine proteins, which trigger neural excitation, muscle spasm, and pain. The close relationship of mast cells to nerves in IBS may similarly give rise to symptoms. Genetic studies also support of the role of innate immunity in FGIDs. The data supporting a prime role for eosinophils and mast cells in subsets of FD and IBS has become credible, and these data should be used to implement advances in diagnosis and therapeutic trials. 2013-01-10T01:40:04.399Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12381 Objectives: To compare the prevalence of gastrointestinal (GI) disorders in rheumatoid arthritis (RA) versus non-RA subjects and to describe determinants of GI disorders in RA. Methods: The bowel disease questionnaire was completed by RA and non-RA subjects. RA patients also completed the health assessment questionnaire (HAQ). Results: The study responders included 284 RA and 233 non-RA subjects. Abdominal pain/discomfort, postprandial fullness, nausea, and stool leakage were significantly more common in RA versus non-RA (odds ratios [OR] = 1.8; 1.9; 4.0; 8.2, resp.). The use of laxatives, proton pump inhibitors, NSAIDs, acetaminophen, and narcotics was more commonly reported in RA versus non-RA (OR = 2.0; 1.7; 3.0; 2.0; 1.9, resp.). Age < 60 and HAQ ≥ 1 were associated with dyspepsia, irritable bowel syndrome, gastroesophageal reflux disease, and GI symptom complex overlap in RA. Conclusion: Several upper and lower GI disorders were significantly more prevalent in RA versus non-RA subjects. Age <60 and physical function impairment (HAQ ≥ 1) were associated with GI disorders in RA. 2013-01-10T01:30:12.196Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12380 Background: Several small series have suggested an increased risk of complications associated with esophageal dilation in patients with eosinophilic esophagitis (EoE). Objective: To quantitate the risk and identify risk factors for esophageal complications in dilation in EoE patients. Design: Retrospective, uncontrolled, single-center study. Setting: Tertiary referral hospital. Patients: A total of 161 EoE patients (mean ± standard deviation age 44.3 ± 15.3 years, 112 men, 49 women, 150 white patients, 10 unknown, 1 Asian). Interventions: Through-the-scope balloon or Savary dilation of EoE. Main Outcome Measurements: The rate of complications defined as deep mucosal tear, major bleeding, or perforation, and determination of risk factors for complications. Results: A total of 293 dilations were performed in 161 patients. Complications reported were deep mucosal tear in 9.2% (n = 27), major bleeding in 0.3% (n = 1), and immediate perforation in 1.0% (n = 3). All patients with perforations were successfully treated medically without surgery (mean ± standard deviation hospital stay 5.3 ± 3.2 days). Factors associated with an increased risk of complications were luminal narrowing in the upper (odds ratio [OR], 5.62; 95% CI, 2.07-15.26; P < .001) and middle third of the esophagus (OR, 4.93; 95% CI, 1.64-14.83; P < .005) compared with lower third, luminal stricture unable to be traversed with a standard upper endoscope (OR, 2.48; 95% CI, 1.06-5.83; P = .037), and use of Savary dilator (OR, 2.63; 95% CI, 1.18-5.83; P = .018). Limitations: Retrospective design, uncontrolled study. Conclusions: Deep mucosal tears are common after dilation (9%), but the risk of immediate transluminal perforation with EoE is approximately 1%. The risk of severe complications is increased in patients with more proximal stricture and strictures that initially prevent endoscope passage. 2013-01-10T01:20:06.276Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12377 Background: There has been increasing interest in small intestinal bacterial overgrowth (SIBO) after reports of a link with irritable bowel syndrome (IBS), yet our understanding of this entity is limited. Aim: Our aim was to estimate the yield of patients undergoing duodenal aspirate culture, and to identify symptoms and features that predict SIBO. Methods: A medical chart review of patients who had undergone duodenal aspirate culture at an academic medical centre in 2003 was performed to record clinical characteristics and culture results. The associations between aspirate results and symptoms, medical diagnoses and medication use were assessed using logistic regression. Results: A total of 675 patients had available aspirate results. Mean age of the sample was 53 (s.d. 17) and 443 (66%) were female patients. Overall, 8% of aspirates were positive for SIBO; 2% of IBS patients had SIBO. Older age, steatorrhoea and narcotic use were associated with SIBO (P < 0.05). PPI use was not associated with SIBO, but was associated with bacterial growth not meeting criteria for SIBO (P < 0.05). Inflammatory bowel disease (IBD), small bowel diverticula and pancreatitis were positively associated with an abnormal duodenal aspirate (P < 0.05), but other conditions including IBS were not associated with SIBO. Conclusion: Older age, steatorrhoea, narcotic use, IBD, small bowel diverticula and pancreatitis were associated with small intestinal bacterial overgrowth based on abnormal duodenal aspirate culture results. However, no clear associations of true small intestinal bacterial overgrowth with IBS or PPI use were detected, in contrast to recent speculation. 2013-01-09T04:50:03.958Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12376 Objectives: The efficacy of 5-aminosalicylic acids (5-ASAs) in ulcerative colitis (UC) has been studied previously in meta-analyses. However, several randomized controlled trials (RCTs) have been published recently, and no previous meta-analysis has studied the effect of 5-ASA dosage used. Methods: MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through December 2010). Eligible trials recruited adults with active or quiescent UC, comparing different doses of 5-ASAs with themselves or placebo. Dichotomous data were pooled to obtain relative risk (RR) of failure to achieve remission in active UC, and RR of relapse of disease activity in quiescent UC, with a 95% confidence interval (CI). The number needed to treat (NNT) was calculated from the reciprocal of the risk difference. Results: The search identified 3,061 citations, and 37 RCTs were eligible. Of these, 11 compared 5-ASA with placebo in active UC remission, with the RR of no remission with 5-ASAs of 0.79 (95% CI 0.73–0.85; NNT=6). Doses of ≥2.0 g/day were more effective than <2.0 g/day for remission (RR=0.91; 95% CI 0.85–0.98). There were 11 RCTs comparing 5-ASAs with placebo in preventing relapse of quiescent UC, with the RR of relapse of 0.65 (95% CI 0.55–0.76; NNT=4). Doses of ≥2.0 g/day appeared more effective than <2.0 g/day for preventing relapse (RR=0.79; 95% CI 0.64–0.97). Conclusions: 5-ASAs are highly effective for inducing remission and preventing relapse in UC. Evidence suggests that doses of ≥2.0 g/day have greater efficacy, although doses >2.5 g/day do not appear to lead to higher remission rates. 2013-01-09T04:40:05.706Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12375 Background: Prevalence of, and risk factors for, noncardiac chest pain in the community have not been well studied. Aims: To conduct a systematic review and meta-analysis to examine these issues. Methods: MEDLINE, EMBASE and EMBASE Classic were searched (up to March 2011) to identify population-based studies reporting prevalence of noncardiac chest pain in adults (≥15 years) according to self-report, questionnaire or specific symptom-based criteria. Prevalence of noncardiac chest pain was extracted for all studies, and according to study location and certain other characteristics including presence or absence of gastro-oesophageal reflux disease (GERD) symptoms, where reported. Pooled prevalence overall, as well as odds ratios (OR), with 95% confidence intervals (CIs) were calculated. Results: Of 18 articles evaluated, 16 reported prevalence of noncardiac chest pain in 14 separate populations, containing 24 849 subjects. Pooled prevalence of noncardiac chest pain in all studies was 13% (95% CI 9–16). The prevalence of noncardiac chest pain was higher in Australian studies and in studies using a questionnaire to define its presence, compared with those using Rome I or II criteria. Prevalence was no different in women vs. men (OR 0.99; 95% CI 0.82–1.20). The prevalence was markedly higher in subjects who also reported GERD (OR 4.71; 95% CI 3.32–6.70) and increased according to frequency of GERD symptoms. Conclusions: Pooled prevalence of noncardiac chest pain in the community was 13%, but there were few studies. Rates did not appear to differ according to gender or age. Presence of GERD was strongly associated with noncardiac chest pain. 2013-01-09T04:20:06.488Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12374 Objectives: Approximately one third of patients with non cardiac chest pain (NCCP) report a history of abuse, however no data exists on the prevalence of abuse among people with unexplained chest pain in the general population. We aimed to determine if there is a relationship between childhood sexual, physical, emotional abuse and unexplained chest pain, and to identify whether any potential relationship is being driven by an association with psychological distress. Methods: Subjects were identified from 2 previous random population surveys that included people with irritable bowel syndrome (IBS) and/or functional dyspepsia (FD) and healthy controls. People in the unexplained chest pain group (n = 27) had chest pain in the past 12 months that was not heartburn or heart disease. People in the comparison group (n = 60) did not have chest pain for more than 12 months. Self-reported abuse and psychological variables were assessed using validated measures. Results: Emotional/verbal abuse (20.8% versus 4.4%, P = 0.032) and physical abuse (16.7% versus 2.2%, P = 0.028) were significantly more common in people with unexplained chest pain versus the comparison group. Only a history of emotional/verbal abuse was a significant independent predictor of meeting criteria for unexplained chest pain (OR = 5.66; 95%CI 1.01–31.80, P = 0.049) even after controlling for IBS and/or FD (OR = 5.45; 95%CI 0.96–30.83, P = .05), but not when depression was controlled for (OR = 4.70; 95%CI 0.90–27.61), P = 0.08. Conclusions: A history of childhood emotional/verbal abuse is a risk factor for having unexplained chest pain but the association may be moderated by psychological distress, specifically depression. 2013-01-09T04:10:04.231Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12373 Background: The causes of irritable bowel syndrome (IBS) remain obscure. Some investigators have proposed chronic low-grade mucosal inflammation as a potential etiological factor. We performed a systematic review to examine this issue in detail. Methods: MEDLINE, EMBASE, and EMBASE classic were searched up to December 2010 to identify studies of case–control design applying tests for low-grade inflammation to either full-thickness intestinal or endoscopic mucosal biopsies from patients with IBS. Controls were required to be healthy individuals, or asymptomatic patients undergoing investigation for reasons other than the reporting of upper or lower gastrointestinal symptoms. Individual study results were summarized descriptively. Results: The literature search identified 1388 citations, of which 16 studies were eligible for inclusion. Individual study results were diverse, partly as a consequence of the different surrogate markers for inflammatory mechanisms studied. Mast cells, T lymphocytes, B lymphocytes, and mucosal cytokine production all appeared altered among cases with IBS in individual studies, while no study demonstrated a significant difference in numbers of plasma cells, neutrophils, or eosinophils. Some studies suggested a relationship between mast cell abnormalities and symptom severity and frequency, as well as co-existent fatigue and depression. Studies were limited by the lack of comparability of controls, and the fact that most were conducted in highly selected groups of patients with IBS. Conclusions: Low-grade mucosal inflammation, particularly mast cell activation, may be a contributory factor in the pathogenesis of IBS. Mast cell stabilizers warrant further assessment as a potential therapy in the condition. 2013-01-09T03:50:05.719Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12372 Background: Although direct medical costs for constipation-related medical visits are thought to be high, to date, there have been no studies examining longitudinal resource utilisation in adults with constipation. Aim: To estimate the incremental direct medical costs associated with constipation in women. Methods: This is a nested case-control study. The study population consisted of all mothers of 5718 children in the population-based birth cohort born during 1976–1982 in a community. The cases presented to the medical facilities with constipation. The controls were randomly selected and matched to cases in a 2:1 ratio. Direct medical costs for constipated women and controls were collected for the years 1987–2002. Results: We identified 168 women with a diagnosis of constipation. The total direct medical costs over the 15-year period for constipated subjects were more than double those of controls [$63 591 (95% CI: 49 786–81 396) vs. $24 529 (95% CI: 20 667–29 260)]. The overall out-patient costs for constipated women were $38 897 (95% CI: 31 381–48 253) compared to $15 110 (95% CI: 12 904–17 781) for controls. The median of annual out-patient visits for constipated women was 0.16 compared to 0.11 for controls. Conclusion: Women with constipation have significantly higher medical care utilisation and expenditures compared with women without constipation. 2013-01-09T03:50:03.633Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10527 OBJECTIVES: The Nepean Dyspepsia Index (NDI) was specifically developed for trials in functional dyspepsia, but the smallest change on the total or subscale scores, which corresponds to a clinically meaningful change (minimal clinically important difference, MCID), has not been established. An MCID has been established for the SF-36 (5 points on physical or mental health subscales); such information is critical for understanding clinical trial data. We aimed at calculating an MCID for the NDI to help guide the interpretation of future clinical trials. METHODS: Comprehensive clinical data were collected in outpatients (n=101) and community subjects (n=460), and the MCID for the NDI total score was examined in three ways. The first estimated the average change (over a 2-week period) in the NDI corresponding to a five-point change in the SF-36 mental and physical subscales, and the second repeated this using a 1-s.d. change in symptom level, whereas the third calculated Cohen's d effect size among individuals changing by at least five points on the SF-36 subscales. A separate cross-sectional study was used to obtain the receiver–operator characteristic curve for discriminating between dyspepsia and non-dyspepsia subjects. RESULTS: Among individuals improving by at least 1 s.d. on the patient-reported symptom score, the corresponding improvement in NDI quality of life (QoL) was an average of 18 points (s.d.=12) compared with only 7 points (s.d.=15) in those with no/minimal change in symptoms, yielding a Cohen d of 1.0 and a proposed MCID of 10 points. Although the same pattern was found using the SF-36 physical scale, the effect size was smaller (Cohen's d=0.25). Smaller effect sizes were also obtained using the SF-36 mental subscale (Cohen's d=0.1) and the physician global assessment (Cohen's d=0.33). In a separate cross-sectional community study, the NDI-QoL score was shown to provide good discrimination between individuals meeting and not meeting the Rome criteria for functional dyspepsia, with an area under the receiver–operator characteristic curve of 0.80 (95 % confidence interval: 0.75, 0.85). CONCLUSIONS: A change of at least 10 points on the NDI total scale corresponds to a clinically meaningful change in patient status. 2012-04-05T04:54:20.032Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10517 Gastroenterologists mainly deal with chronic organic and functional illnesses that are not life threatening but can be expensive to treat. How this compares with the management of other diseases that cause significant mortality is an important question to answer if health-care resources are to be allocated appropriately. Comparing health care in terms of cost per quality adjusted life year (QALY) gained is one approach to this problem although there are concerns about whose values should be elicited and how QALYs are measured. 2012-03-26T04:10:19.120Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10450 The esophagus and stomach have specific motor functions that propel ingested material through the upper gastrointestinal tract, while the stomach also helps to grind the food into a more digestible form. The proximal, striated muscle portion of the esophagus quickly moves the bolus into the distal esophagus where smooth muscle contractions propel it through the lower esophageal sphincter into the stomach. In addition to allowing the bolus to pass, the lower esophageal sphincter is tonically contracted in its resting state, which prevents gastroesophageal reflux. The proximal stomach receptively relaxes to accommodate the swallowed bolus, while the distal stomach has functions to grind the food into smaller sizes to facilitate digestion. The antrum and pylorus have an additional function as a “sieve” to prevent emptying of particles until they have been reduced to an appropriate size. The stomach has a specific region that coordinates the motor activity of the stomach and to a degree the entire upper gastrointestinal tract (pacemaker region). This region initiates the periodic contraction profile that pushes both digested and undigested material through the gastrointestinal tract (phase III of the migrating motor complex). This complicated physiology is affected by both hormones and extrinsic innervation, but the pacemaker resides in the specialized nervous system of the gastrointestinal tract, most likely in the interstitial Cajal cells. 2012-03-20T02:00:03.961Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10428 Eosinophilic gastroenteritis (EG) is a rare and heterogeneous disorder characterized by gastrointestinal (GI) symptoms and eosinophilic infiltration of the GI tract. Symptoms are dependent upon site of the GI tract involved and depth of involvement. The diagnostic criteria include: (i) the presence of GI symptoms, (ii) histopathology demonstrating predominant eosinophilic infiltration, (iii) the absence of other conditions that cause eosinophilia, and (iv) no eosinophilic involvement of organs outside the GI tract. Diagnosis requires a clinical history, physical exam, and documentation of any history of atopic disorders, allergies, and drug allergies. Laboratory evaluation includes a complete blood count with differential to evaluate for peripheral eosinophilia. Endoscopic evaluation with random biopsies remains the cornerstone for diagnosis. Histopathologic diagnosis typically requires an infiltration level of 20 or more eosinophils per high power field. Management strategies are based upon severity of symptoms and include antidiarrheals, dietary adjustments, and steroid therapy. 2012-03-19T00:20:05.827Z ]]>