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Contemporary systems for the diagnosis and management gastrointestinal symptoms not attributable to organic diseases (Functional GI Disorders, FGID, now renamed Disorders of Gut-Brain Interaction, DGBI) seek to categorize patients into narrowly defined symptom-based sub-classes to enable targeted treatment of patient cohorts with similar underlying putative pathophysiology. However, an overlap of symptom categories frequently occurs and has a negative impact on treatment outcomes. There is a lack of guidance on their management. An Asian Pacific Association of Gastroenterology (APAGE) working group was set up to develop clinical practice guidelines for management of patients with functional dyspepsia (FD) who have an overlap with another functional gastrointestinal disorder: FD with gastroesophageal reflux (FD-GERD), epigastric pain syndrome with irritable bowel syndrome (EPS-IBS), postprandial distress syndrome with IBS (PDS-IBS), and FD-Constipation. We identified putative pathophysiology to provide a basis for treatment recommendations. A management algorithm is presented to guide primary and secondary care clinicians. ispartof: JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY vol:38 issue:2 pages:197-209 ispartof: location:Australia status: published

Infrequent bowel movements are a common feature of constipation, but fecal loading as a cause of symptoms in patients with regular bowel movements has not previously been evaluated. The aim of this preliminary study was to assess prospectively if fecal loading may be a cause of bowel symptoms in patients with regular bowel movements. Consecutive patients attending a gastroenterology clinic for functional bowel symptoms (FBD) not including infrequent bowel movements and who did not fulfil the criteria for constipation-predominant irritable bowel syndrome or functional constipation underwent plain abdominal radiography. Those with fecal loading received dietary advice and laxative treatment. The reproducibility of determination of fecal loading using the Leech score was assessed ‘blindly’ by a consultant radiologist. Twenty-six of 74 patients with FBD but not infrequent bowel movements had fecal loading demonstrated on abdominal radiology. Their Leech scores were significantly higher than those of control patients matched for age, sex and hospital (median 6 vs. 4, IQR 5–7 vs. 3.5–5, p

BACKGROUND AND AIM Singapore is a multi-ethnic country that has undergone rapid development over the last few decades, with increasing influence of western culture, and faces an aging population. Previously, a varying prevalence of colonic diverticulosis (CD) was reported by a few small studies. This study aims to evaluate the prevalence of CD in Singapore and identify associations with common gastrointestinal symptoms and risk factors. METHODS We reviewed retrospective data of 20 395 consecutive colonoscopies performed from 2006 to 2016 for presence of CD and indications of screening, diarrhea, constipation, and abdominal pain. RESULTS The prevalence of CD progressively increased from 2006 to 2016 (14.9% vs 23.9%, adjusted trend

To clarify whether there were any significant differences in clinical symptoms and eating patterns between functional dyspepsia (FD) patients and FD with pancreatic enzyme abnormalities (FD-P) patients as refractory FD, we compared these factors in multicenter studies in Singapore and Japan.One hundred ninety-eight consecutive patients presenting with FD (n = 88), FD-P patients (n = 81) based on Rome III classification and controlled group (n = 39) recruited from six institutions in Singapore and Japan. Clinical characteristics, clinical symptoms for dietary fat intake, and eating behaviors were estimated using questionnaires. Anxiety and health-related quality of life were determined by STAI-state/-trait and SF-8, respectively.There were no significant differences in age, sex, BMI, smoking, alcohol intake, past medical history, and history of allergy in FD and FD-P patients between Singapore and Japan. There were no significant differences in FD subtypes, gastrointestinal symptom rating scale score, severity of FD symptoms, and eating pattern in Singapore and Japan. Moreover, there were significant differences in certain eating behaviors between FD and FD-P patients in Singapore and Japan. Interestingly, epigastric pain and early satiety following fat meals in FD-P patients were significantly (P = 0.003 and P = 0.008, respectively) higher compared with those in FD patients in Japan. Physical component score in FD-P patients was significantly (P = 0.019) disturbed compared with those in FD patients in Japan.Epigastric pain and early satiety following fat meals in FD-P patients may be useful tools to differentiate FD-P patients from FD patients in Japan.

Background and aims The efficacy of herbal medicines (HMs) for functional gastrointestinal disorders (FGIDs) including irritable bowel syndrome (IBS), functional dyspepsia (FD) and functional constipation (FC) is controversial. A systematic review with meta-analysis was conducted to determine their effectiveness for FGIDs. Methods We searched the following electronic databases till July 2019 with English language restriction: The Cochrane Library, EMBASE and PUBMED. Randomized double-blind controlled trials of HMs compared with placebo or conventional pharmacological drugs for adult FGIDs patients were included. Results In total, 49 trials involving 7396 participants with FGIDs were included. The risk of bias was low in 9, unclear in 36, and high in 4 trials. More than 33 different herbal formulae were tested. HMs demonstrated statistically significant benefits for symptom improvement compared with placebo in 46 trials (RR = 1.67, 95% CI 1.48-1.88). When compared with conventional pharmacological therapy in 5 trials, HMs were found to be non-inferior (RR = 1.10, 95% CI 1.03-1.18). The number of trials with regards to FD, IBS and FC were 19, 23 and 7 respectively. Subgroup analysis found that HMs were better than placebo in alleviating symptoms for FD (RR = 1.50, 95% CI 1.32-1.69), IBS (RR = 1.62, 95% CI 1.32-1.97) and FC (RR = 3.83, 95% CI 2.26-6.50). HMs tended to have more patients with adverse events than placebo, but similar to conventional pharmacological drugs. Conclusions Our findings provide a positive signal for HMs as a potentially well-tolerated and effective treatment for FGIDs, deserving further examination in high-quality trials.

The concept of consuming microorganisms in the treatment of a medical condition and in health maintenance has gained much attraction, giving rise to an abundance of medical claims and of health supplements. This study identified relevant clinical questions on the therapeutic use of probiotics and reviewed the literature in irritable bowel syndrome, inflammatory bowel disease, impaired intestinal immunity, liver disease, intestinal infections, and common childhood digestive disorders. Statements were developed to address these clinical questions. A panel of experienced clinicians was tasked to critically evaluate and debate the available data. Both consensus and contentious statements are presented to provide to clinicians a perspective on the potential of probiotics and importantly their limitations.

Background and aim Surgery and other non-pharmacological treatments such as sacral nerve stimulation are used for the treatment of difficult-to-treat chronic constipation. Novel pharmacological therapeutic agents are also being introduced. To evaluate the efficacy of these treatments, it is imperative to have a consistent definition of pharmacologically refractory constipation. A systematic review of studies on refractory, difficult-to-treat or surgically treated constipation was carried out to determine the criteria that various authors used to define this group of patients. Methods A systematic review was performed for literature published from June 2005 to June 2015 using PubMed, Cochrane, and Scopus databases, as well as manual searches. Studies on patients with refractory or intractable constipation were extracted. Criteria used for defining refractory constipation, as well as pharmacological agents tried including dosage, frequency, and duration, were reviewed. Results Sixty-one studies were included in this review. Forty-eight involved surgical treatment of constipation, while 13 examined non-surgical therapies for refractory constipation. There is no generally accepted definition of refractory constipation. Authors consider constipation to be refractory when response to management is suboptimal, but there is no consensus on the choice of drug, order of usage, and dosage or treatment duration. Prior medical therapy was not mentioned at all in five studies. Conclusions There is need for a detailed definition of pharmacologically refractory constipation before submitting patients to invasive treatments and to evaluate new pharmacological agents.

The Asia-Pacific region is diverse, with regard to ethnicity, culture, and economic development incorporating some of the world's least and most developed nations. Gastrointestinal diseases are common in the Asia-Pacific region, and their prevalence, presentation, and management vary considerably within the region. There is growing evidence for an important role for the human gut microbiota in gastrointestinal health. As a consequence, geographic variations in the composition of the gut microbiota may contribute to variations in both the prevalence and response to therapy of specific diseases. Probiotics have been proposed as a valuable option in the prevention and treatment of a number of gastrointestinal illnesses, but the quality of available evidence to support their efficacy is variable. A meeting of international experts in adult and pediatric gastroenterology was held at the Sorbonne University, Paris, France, on April 11 and 12, 2016, to discuss current evidence supporting the use of probiotics in gastrointestinal disorders in the Asia-Pacific region. This article provides an overview of the discussions held at this meeting and recommends the formation of an Asia-Pacific Consortium on Gut Microbiota similar to those established in Europe and North America.

Historically, the epidemiology of gastrointestinal diseases in Asia was different from that in Western countries. Early studies suggested a low prevalence of irritable bowel syndrome (IBS) in Asia. As the diagnosis of IBS is symptom-based and as symptom perception, expression, and interpretation are influenced by sociocultural perspectives including language, the presentation of IBS is expected to vary in different communities. Furthermore, the pathogenesis is multifactorial with psychosocial (stress, illness, behavior, and diet) and biological (infection, gut microbiota, and immune activation) variables interacting, and so, the present study can anticipate that the development of IBS will vary in different environments. In recognition of this aspect of functional gastrointestinal disorders, the recently published Rome IV documents have provided greater focus on cross-cultural factors. In this review, the present study seeks to highlight Asian perspectives by identifying historical trends and recent publications from the region and comparing these with the observations from Western societies.

Background and Aim Information on real world treatment experiences of patients with functional bowel disorders is lacking from Asia. This study aimed to describe the medication exposure and treatment satisfaction of patients presenting to gastroenterology clinics across a sampling of Asian cities. Methods From March 2011 to October 2013, adult patients presenting to hospital-based gastroenterology outpatient clinics in 11 cities across Asia, who fulfilled screening criteria for any functional gastrointestinal disorder, were asked to complete a validated culturally adapted translation of the Rome III diagnostic questionnaire, a checklist of medications received in the preceding 3 months and questions on treatment satisfaction. Results A total of 1376 patients (female 755, male 621, 41.36 ± 13.25 years) comprising irritable bowel (621, 45.1%), unspecified functional bowel disorder (372, 27.8%), functional constipation (202, 14.7%), functional bloating (144, 10.5%), and functional diarrhea (56, 4.1%) completed the study. Of 1105 patients with a previous consultation, 509 (46.1%) were dissatisfied with their treatment, with ineffective treatment being the commonest reason. Satisfaction with previous consultation was lowest by diagnosis for functional constipation (29.2%), and the most bothersome symptom was straining (37.5%). Of 1046 patients who had taken medications for their gastrointestinal symptoms in the last 3 months, 793 (75.8%) had received two or more drugs. For irritable bowel syndrome patients, treatment with proton pump inhibitors and antispasmodics was recorded in 57% and 31%, with overlapping epigastric pain and heartburn predicting proton pump inhibitors use. Conclusions More attention should be given to treatment gaps with regards to possible under-treatment with antispasmodics in irritable bowel syndrome and to critically evaluating the efficacy of constipation management.

Evidence is emerging that IBS, a hitherto enigmatic disorder thought to be predominantly related to psychological factors, has a microorganic basis in a subset of patients with the disease. Post-infectious IBS (PI-IBS), commonly of the diarrhoea-predominant subtype (defined as new development of IBS following acute infectious diarrhoea), is one such condition known to occur in up to 10-30% individuals after acute gastroenteritis. However, following acute infectious gastroenteritis, patients can also develop post-infectious malabsorption syndrome (PI-MAS), popularly known as tropical sprue. As no study on PI-IBS has rigorously excluded tropical sprue by appropriate investigations, including small intestinal biopsy, the frequency of tropical sprue among patients with PI-IBS is not known. Small intestinal bacterial overgrowth (SIBO) has been suggested to be associated with IBS in general, and in particular diarrhoea-predominant IBS, including PI-IBS. SIBO is also known to be associated with tropical sprue. As both IBS, particularly the subset probably associated with SIBO, and tropical sprue improve with antibiotic treatment, we provide evidence and an explanatory model to support a link among these disorders.

Summary Background Cross-cultural, multinational research can advance the field of functional gastrointestinal disorders (FGIDs). Cross-cultural comparative research can make a significant contribution in areas such as epidemiology, genetics, psychosocial modulators, symptom reporting and interpretation, extra-intestinal co-morbidity, diagnosis and treatment, determinants of disease severity, health care utilisation, and health-related quality of life, all issues that can be affected by geographical region, culture, ethnicity and race. Aims To identify methodological challenges for cross-cultural, multinational research, and suggest possible solutions. Methods This report, which summarises the full report of a working team established by the Rome Foundation that is available on the Internet, reflects an effort by an international committee of FGID clinicians and researchers. It is based on comprehensive literature reviews and expert opinion. Results Cross-cultural, multinational research is important and feasible, but has barriers to successful implementation. This report contains recommendations for future research relating to study design, subject recruitment, availability of appropriate study instruments, translation and validation of study instruments, documenting confounders, statistical analyses and reporting of results. Conclusions Advances in study design and methodology, as well as cross-cultural research competence, have not matched technological advancements. The development of multinational research networks and cross-cultural research collaboration is still in its early stages. This report is intended to be aspirational rather than prescriptive, so we present recommendations, not guidelines. We aim to raise awareness of these issues and to pose higher standards, but not to discourage investigators from doing what is feasible in any particular setting.

Summary Background Coeliac disease (CD), originally thought to be largely confined to Northern Europe and Australasia and uncommon in North America and the Middle East, is now recognised to be equally common in all these countries. It is still thought to be rare in the Orient and Sub-Saharan Africa. Aim To assess geographical differences and time trends in the frequency of CD. Methods Medline and Embase searches were conducted on 10 November 2012, from 1946 and 1980 respectively, using the key words: coeliac disease or celiac disease + prevalence or incidence or frequency. Results There were significant intra- and inter-country differences in the prevalence and incidence of CD. Only 24 ethnic Chinese and Japanese patients have been reported in the English literature. Of CD-associated HLA DQ antigens, DQ2 occurs in 5–10% of Chinese and sub-Saharan Africans, compared to 5–20% in Western Europe. DQ8 occurs in 5–10% of English, Tunisians and Iranians, but in

Background and Aim Chronic constipation is usually associated with young women, and urinary and sexual dysfunction has been reported as co-morbidity. Elderly men also appear to suffer from chronic constipation, as well as lower urinary tract symptoms and erectile dysfunction, but their association as co-morbidity has not been studied in the community. The aim of the present study was to determine the prevalence of bowel symptoms in our community with particular reference to the association with urinary and sexual dysfunction in the male population. Methods A population-based cross–sectional survey involving 2276 subjects (1143 male, 1133 female) representative of the Singapore population demographics was conducted to evaluate the prevalence of chronic bowel disturbances, lower urinary tract symptoms (LUTS), and erectile dysfunction (ED). Results The prevalence of chronic constipation was 25.1% overall, with the highest in men aged ≥ 70 years (35.8%) followed by women aged 20–29 years (30.5%). The commonest symptoms reported in chronic constipation were hard stool (95.1%), straining (90.9%) and incomplete evacuation (53.8%). Bloating was often experienced by 25.5% of the community, among whom 61.1% had some form of bowel disturbance. In men aged ≥ 30 years, LUTS (7.8% v 3.1%) and ED (60.5% v 48.6%) were more common in men with than without chronic constipation; constipation was an independent predictor of ED. Conclusions In this Asian urban community, chronic constipation was more common than previously suspected, and urinary and erectile dysfunction were found to be co-morbidity in men.

Background and Aim: Environmental factors such as food, lifestyle and prevalence of Helicobacter pylori infection are widely different in Asian countries compared with the West, and physiological functions and genetic factors of Asians may also be different from those of Westerners. Establishing an Asian consensus for functional dyspepsia is crucial in order to attract attention to such data from Asian countries, to articulate the experience and views of Asian experts, and to provide a relevant guide on management of functional dyspepsia for primary care physicians working in Asia. Methods: Consensus team members were selected from Asian experts and consensus development was carried out by using a modified Delphi method. Consensus teams collected published papers on functional dyspepsia especially from Asia and developed candidate consensus statements based on the generated clinical questions. At the first face-to-face meeting, each statement was reviewed and e-mail voting was done twice. At the second face-to-face meeting, final voting on each statement was done using a keypad voting system. A grade of evidence and strength of recommendation were applied to each statement according to the method of the GRADE Working Group. Results: Twenty-nine consensus statements were finalized, including seven for definition and diagnosis, five for epidemiology, nine for pathophysiology, and eight for management. Algorithms for diagnosis and management of functional dyspepsia were added. Conclusions: This consensus developed by Asian experts shows distinctive features of functional dyspepsia in Asia and will provide a guide to the diagnosis and management of functional dyspepsia for Asian primary care physicians.

Background and Aims: Many of the ideas on irritable bowel syndrome (IBS) are derived from studies conducted in Western societies. Their relevance to Asian societies has not been critically examined. Our objectives were to bring to attention important data from Asian studies, articulate the experience and views of our Asian experts, and provide a relevant guide on this poorly understood condition for doctors and scientists working in Asia. Methods: A multinational group of physicians from Asia with special interest in IBS raised statements on IBS pertaining to symptoms, diagnosis, epidemiology, infection, pathophysiology, motility, management, and diet. A modified Delphi approach was employed to present and grade the quality of evidence, and determine the level of agreement. Results: We observed that bloating and symptoms associated with meals were prominent complaints among our IBS patients. In the majority of our countries, we did not observe a female predominance. In some Asian populations, the intestinal transit times in healthy and IBS patients appear to be faster than those reported in the West. High consultation rates were observed, particularly in the more affluent countries. There was only weak evidence to support the perception that psychological distress determines health-care seeking. Dietary factors, in particular, chili consumption and the high prevalence of lactose malabsorption, were perceived to be aggravating factors, but the evidence was weak. Conclusions: This detailed compilation of studies from different parts of Asia, draws attention to Asian patients' experiences of IBS.

Recently, there has been strong interest in the therapeutic potential of probiotics for irritable bowel syndrome (IBS). At the same time, there is a rapidly growing body of evidence to support an etiological role for gastrointestinal infection and the associated immune activation in the development of post-infectious IBS. In a more controversial area, small intestinal bacterial overgrowth has been associated with a subset of patients with IBS; the issue of whether it is appropriate to treat a subset of IBS patients with antibiotics and probiotics is currently a matter for debate. Thus, it appears that the gastrointestinal microbial flora may exert beneficial effects for symptoms of IBS under some circumstances, while in other situations gut microbes could give rise to symptoms of IBS. How do we make sense of the apparently diverse roles that 'bugs' may play in IBS? To address this question, we have conducted an in-depth review, attempting where possible to draw lessons from Asian studies.

In this review we have unearthed epidemiological data that; support the 'old' concept of irritable bowel syndrome (IBS) as a disorder of civilization, build a 'new' symptom profile of IBS for Asia, and persuade us against the use of 'borrowed' Western diagnostic criteria and illness models by Asian societies. In the 1960s, IBS was described as a disorder of civilization. Early studies from Asia suggested a prevalence of IBS below 5%. Recent studies from Asia suggest a trend for the more affluent city states like Singapore and Tokyo, to have higher prevalence of 8.6% and 9.8%, respectively, while India had the lowest prevalence of 4.2%. Furthermore, there was a trend among the better educated and more affluent strata of society in several urban Chinese populations for a higher prevalence of IBS, as well as a trend for a higher consultation rate. Across Chinese and Indian predominant populations, a majority of patients with IBS criteria report upper abdominal symptoms such as epigastric pain relieved by defecation, bloating and dyspepsia. Bloating and incomplete evacuation appear to be more important determinants of consultation behavior, than psychological factors. The failure of the Rome criteria to recognize the relationship to meals, may have led to a substantial misclassification of IBS as dyspepsia. The relevance of the Western model of psychological disturbance as a determinant of consultation behavior is questionable because of the accessibility and acceptability of medical consultation for gastrointestinal complaints in many Asian communities.

Objectives/Background The role of Helicobacter pylori infection in functional dyspepsia (FD) remains controversial. Several randomized controlled trials involving populations in the West, observed no statistically significant advantage over placebo. However, none of these studies involved Asian populations which have high infection rates. Methods A double blind, randomized, placebo-controlled trial of H. pylori eradication for FD was conducted in our Singapore-based Asian population. Forty-one patients received active treatment consisting of a 1-week course of omeprazole 20 mg once daily, clarithromycin 250 mg twice daily and tinidazole 500 mg twice daily whereas another 41 patients received matching placebo tablets. A dyspepsia score was derived by grading 5 dyspeptic symptoms on a Likert scale. Symptom assessment and urea breath test were repeated at 6 weeks, 6 and 12 months from the start of treatment. The primary end point was symptom resolution, defined as a dyspepsia score of 0 or 1 at the end of 12 months follow-up. Results On intention-to-treat analyses, symptom resolution was observed in 24% of patients on active treatment and 7% on placebo; the difference in proportion of patients with symptom resolution was statistically significant (P=0.02, 95% confidence interval: 1.1-17.7). H. pylori eradication rates perprotocol and intention-to-treat were 80.0 and 68.3%, on active treatment and 5.6 and 4.9% on placebo (both P values

Aim: To determine the inter-observer agreement and validity of the LA Classification in scoring the severity of esophagitis in Asian patients. Methods: Video endoscopy clips were selected from 45 consecutive patients participating in reflux studies. The videos were viewed by endoscopists who then independently scored the presence, severity and distribution of esophagitis, including endoscopically suspected Barrett's esophagus (ESBE). Each video was discussed and a consensus on findings reached. Kappa (k) correlation was calculated to describe inter-observer agreement. Results: Thirty-five clips were scored (no esophagitis 20%, grade-A 54%, grade-B 23%, grade-C 3%, respectively and 10 clips were excluded for poor imaging). Excellent agreement was noted on the presence of esophagitis (mean k = 0.79, range 0.77–0.82). Fifteen patients (42%) had ESBE with a mean k of 0.48 (range 0.39–0.60). Inter-observer agreement on the LA grade was good (mean k = 0.58, range 0.55–0.63), whilst in agreement between endoscopists and consensus grading, the mean kappa rose to 0.77 (range 0.73–0.81). There was a trend of increasing agreement as viewings progressed, with superior kappa correlation after 16 cases. Evaluation of the extent of esophagitis showed good k values using the alternative approach of grouping by circumferential extent (mean k = 0.64, range 0.60–0.67) at the lower categories of severity. Conclusions: Scoring using the LA classification for esophagitis and the concurrence on the presence of ESBE showed moderate to strong agreement amongst Asian endoscopists. Our results also suggested that an alternative method of scoring esophagitis based on proportion of circumferential involvement was reliable. A learning effect was observed and reliable scoring was achieved after 16 patients.

Summary Background Prompt endoscopy should be considered as an initial strategy for uninvestigated dyspepsia in the background of high prevalence of Helicobacter pylori infection and malignancy. However, with changes of disease patterns and dyspepsia definition, the prevalence of organic lesions at endoscopy in dyspepsia patients and the predictive values of alarm features and age for in malignancy remain unclear in Asian population. Aims To evaluate the appropriateness of prompt endoscopy as an initial dyspepsia management strategy, we investigated the organic lesion detection rates in Asian dyspepsia patients as well as the diagnostic accuracies of alarm features and age thresholds for malignancy. Methods Literature was retrieved from MEDLINE, PubMed, Embase, Cochrane Library and CINAHL Plus. The prevalence rates of organic lesions and young cancer patients among dyspeptic patients and the sensitivities, specificities, likelihood ratios and diagnostic odds ratio (DOR) of alarm features and ages were estimated. The summary receiver operating characteristic curve was constructed and the area under the curve (AUC) calculated. Subgroup, sensitivity and meta-regression analyses were performed. Results Of the 18 included studies, 15 reported organic lesion detection rates, and six and five analysed the predictive values of alarm features and ages respectively. The overall malignancy detection rate was 1.3% (95% CI: 0.80–2.10). Among cancer patients, 17.8% (95% CI: 10.90–29.00) were younger than 45 years and 3.0% (95% CI: 2.50–3.50) were younger than 35 years. The diagnostic accuracy of alarm features for predicting malignancy was moderate (DOR: 4.87, 95% CI: 2.72–8.71; AUC = 0.74). The diagnostic accuracy at age >35 years (DOR: 9.41, 95% CI: 7.89–11.21; AUC = 0.82) was better than that at age >45 years (DOR: 3.50, 95% CI: 2.32–5.27; AUC = 0.70). Conclusions The malignancy detection rate and proportion of young cancer patients were high among Asian dyspepsia patients. Alarm features and age were of limited value for predicting malignancy, and prompt endoscopy should be considered as the initial strategy for dyspepsia in Asian populations. The optimal age threshold for endoscopy screening in Asia might be 35 years.

OBJECTIVE Isotope ratio mass spectrometry (IRMS) is the accepted method for accurately measuring the 13CO2:12CO2 ratio in the non-invasive and non-radioactive [13C]urea breath test (13C-UBT) for Helicobactor pylori. The IRMS instrument, an expensive and highly specialized analyser, is rarely available. The objective of this project was to modify and validate the use of a simple bench-top gas chromatograph-mass selective detector (GC-MSD) for 13C-UBT. METHODS Breath samples from 71 patients were taken at baseline and 30 min after ingestion of 100 mg [13C]urea. The breath samples were analysed using GC-MSD in the selected ion monitoring mode. The reference 13CO2:12CO2 ratio was from NBS19 obtained from the US National Institute of Standards and Technology. 13CO2:12CO2 ratios of the breath samples were determined. Excess delta per thousand (per mil, delta/thousand) of the 30 min sample over the baseline (deltadelta/thousand) of > or = 6deltadelta/thousand was considered H. pylori positive. Results from 13C-UBT and histology determined blind to each other were compared. RESULTS The coefficient of variation of the reference 13CO2:12CO2 ratio was 0.06%. Using histology as the 'gold standard', the sensitivity (97.9%) and specificity (95.8%) of the GC-MSD 13C-UBT were comparable to those of other methods of H. pylori diagnosis. CONCLUSION A gas chromatograph coupled to a mass selective detector that is available in many analytical and biomedical laboratories can be used for the 13C-UBT. This method will increase the availability and reduce the cost of this non-invasive, non-radioactive diagnostic test.

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

The aim of the present study was to determine the pattern of structural and functional disorders encountered in an Asian gastroenterological clinic and to compare this pattern with findings from Western centres. Consecutive new patients (totalling 2384) attending the clinics of two consultant gastroenterologists were studied. Of these, 2141 suffered from gastroenterological problems. One thousand and sixty-three (49.6%) had structural diseases, the commoner ones being liver disease, peptic ulcer, malignancy, haemorrhoids and gallstones. The remainder who were found to have no structural disease (n = 1078; 50.4%) were deemed to have functional disorders including non-ulcer dyspepsia, irritable bowel, simple constipation and functional diarrhoea. The proportions of functional and structural disease were similar to those in the West. Major differences included a higher frequency of hepatoma and a lower frequency of inflammatory bowel disease and gastro-oesophageal reflux in the present series.

Objectives The role of melatonin in regulating gut motility in human subjects is not clear. The aim of this study was to investigate the effects of exogenous melatonin on colonic transit time (CTT) in healthy subjects and in patients with irritable bowel syndrome (IBS). Methods Colonic transit time was measured in 17 healthy controls using the radio-opaque, blue dye, and Bristol stool form score method before and after 30 days of melatonin treatment 3 mg daily. A double blind cross-over study aimed at measuring CTT was also performed in 17 matched IBS patients using the blue dye and Bristol stool form score methods. The patients were randomized and received either melatonin 3 mg or placebo daily for 8 weeks, followed by a 4-week washout, and then placebo or melatonin in the reverse order for a second 8-week period. Results The melatonin treatment of the control subjects caused an increase in CTT (mean ± SD) from 27.4 ± 10.5 to 37.4 ± 23.8 h (P = 0.04). Compared with the CTT of the controls (25.2 ± 7.7), that of the constipation-predominant IBS patients appeared prolonged—65.2 ± 33.3 h (P

The paper by Sperber et al. in this issue is an early evaluation of the Rome III criteria against the Rome II criteria for irritable bowel syndrome that throws up several important observations. A three to four-fold increase was observed in irritable bowel syndrome prevalence with the Rome III criteria. Individuals with the Rome II criteria had more doctor visits, perception of stress and a negative global feeling. There could be a shift of individuals between irritable bowel syndrome and other functional bowel disorder diagnostic groups such as functional constipation and functional bloating. In this review, it is suggested that rigid application of the symptom frequency and duration requirements of the older Rome criteria could have introduced a selection bias for patients with greater psychological disturbance, and that this could have impacted negatively on our perception and management of irritable bowel syndrome. The findings of Sperber et al. suggest that the new Rome III criteria may enable us to pay more attention to the average irritable bowel syndrome patient we see in our clinics as opposed to the chronically severe patient. It is proposed that improved management of our average patient may translate into better outcomes in terms of reduction in specialist referral, unnecessary surgery and potentially harmful alternative treatments.

Objectives Chronic constipation/idiopathic constipation is highly prevalent in western countries and traditional treatments are suboptimal. This multicenter study evaluated the efficacy and safety of tegaserod, a selective 5-HT(4) agonist and promotility agent, in men with chronic constipation. Methods After screening and baseline phases, men with chronic constipation were randomized to receive either tegaserod 6 mg twice daily or placebo in a double-blind manner for 12 wk. Patients recorded symptoms using a diary. Primary efficacy variable was the response rate for an increase in complete spontaneous bowel movements (CSBMs) during the first 4 wk of double-blind treatment. Other efficacy measures included patient assessment of symptoms and satisfaction with symptom relief. Safety and tolerability were also evaluated. Results In total, 322 patients were randomized to tegaserod (N = 158) or placebo (N = 164). Increases of at least one CSBM per wk during the first 4 wk of treatment observed for tegaserod compared with placebo (40.5%vs 29.3%, P= 0.03) were sustained throughout the 12-wk treatment period. Response rate for CSBM was also superior for tegaserod (P= 0.04 vs placebo) over the treatment period. Benefits for tegaserod over placebo were also observed for some secondary efficacy variables, however, statistical significance was not achieved at all weeks. Frequency of adverse events was similar with tegaserod and placebo. Conclusions Tegaserod 6 mg twice daily was effective and well tolerated in the treatment of chronic constipation in men. Tegaserod provided rapid relief of constipation within 1 wk and the effects were sustained for up to 12 wk.

To compare the frequency and severity of bowel disturbances between rotating shift and regular day nurses and to determine whether functional bowel disorders (FBD) were related to sleep disturbances.Sixty regular day and 58 rotating shift nurses answered three standardized questionnaires: the Gastrointestinal Symptom Questionnaire; the Hospital Anxiety and Depression Scale; and the Irritable Bowel Syndrome Symptoms Evaluation Questionnaire, which included the Sleep Questionnaire, on the frequency and severity of gastrointestinal symptoms, sleep disturbances and psychological distress. Responses to these questions were numerically rated and the sums of individual symptom scores under the respective categories were computed and analysed using statistical tests, as appropriate.Although 22 out of 58 rotating shift nurses (38%) had FBD, only 12 out of 60 regular day nurses (20%) had it (P=0.04). The mean FBD symptom score (P0.002), sleep disturbance score (P0.0001) and anxiety score (P0.002) were all significantly higher among the rotating shift nurses. FBD symptom scores were positively correlated with the sleep disturbance (P=0.0001), anxiety (P=0.0001), depression (P=0.0001), well-being (P=0.0001), fatigue (P=0.0001), and somatic pain scores (P=0.0001). Sleep disturbance (P=0.04), decreased well-being (P=0.04), anxiety (P=0.02), and somatic pain (P=0.03) were independent predictors of FBD symptoms.FBD were more common and severe among rotating shift nurses. The FBD symptom score was positively and independently correlated with the sleep disturbance score, suggesting that poor sleep might be associated with increased FBD symptoms in rotating shift nurses.

Summary Background : Melatonin is involved in the regulation of gastrointestinal motility and sensation. Aim : To determine the potential therapeutic effects of melatonin in irritable bowel syndrome (IBS). Method : Seventeen female patients satisfying the Rome II criteria for IBS were randomized to receive either melatonin 3 mg nocte or identically appearing placebo 1 nocte for 8 weeks, followed by a 4-week washout period and placebo or melatonin in the reverse order for another 8 weeks. Three validated questionnaires – the GI symptom, the sleep questionnaires and the Hospital Anxiety and Depression Scale – were used to assess symptom severity and to compute the IBS, sleep and anxiety/depression scores, respectively. Results : Improvements in mean IBS scores were significantly greater after treatment with melatonin (3.9 ± 2.6) than with placebo (1.3 ± 4.0, P = 0.037). Percent response rate, defined as percentage of subjects achieving mild-to-excellent improvement in IBS symptoms, was also greater in the melatonin-treated arm (88% vs. 47%, P = 0.04). The changes in mean sleep, anxiety, and depression scores were similar with either melatonin or placebo treatment. Conclusions : Melatonin is a promising therapeutic agent for IBS. Its therapeutic effect is independent of its effects on sleep, anxiety or depression.

Summary Background : Data on Asian patients who present with reflux symptoms to their primary care physicians are limited. Aim : To determine whether empirical therapy without endoscopy is appropriate for patients who present to their primary care physicians with uninvestigated reflux symptoms without alarm symptoms. Method : Forty-seven patients presenting with uninvestigated, dominant reflux symptoms but without alarm features to their primary care physicians underwent endoscopy within 2 weeks of referral. Their endoscopic findings were compared with those of 162 primary care patients presenting with uninvestigated dominant dyspepsia. All patients, except those with ulcers, were treated with esomeprazole 20 mg b.d. for 2 weeks. Their treatment response was assessed at 2 weeks using a symptom score. Results : Among patients with dominant reflux symptoms, 14 (30%) had erosive oesophagitis. No other clinically significant endoscopic findings were detected among them. In contrast, erosive oesophagitis and peptic ulcer were found in 13 (8%, P

To study the epidemiology, symptom characteristics and impact of IBS in an urban Asian population.A validated bowel symptom questionnaire was administered at face-to-face interviews to a random sample of 3,000 households in Singapore.The response rate was 78.2% (n = 2,276, 1,143 males and 1,133 females). The age, sex, and racial distribution of our respondents were similar to the general population and there was no significant difference between respondents and nonrespondents by type of household. The prevalence of IBS was 11.0%, 10.4%, and 8.6% by Manning (1 criteria), Rome I and Rome II criteria, respectively. There was a higher prevalence of IBS in those50 years of age (9.7%vs 5.8% 50 oryears, p = 0.002), with more than 6 years of education (9.8%vs 5.9% 6 year or, p = 0.002) and living in landed property (16.8%vs 8.2% living in apartments and public housing, p = 0.008). There was no striking preponderance of female IBS subjects. Chronic constipation was a more common bowel disturbance than chronic diarrhea among our IBS subjects (51.0%vs 12.8%).The prevalence and impact of IBS in our Asian urban society are greater than previously appreciated. We believe that our results provide a useful window to the future trends of gastrointestinal diseases for health and education authorities in developing Asian countries to look into.

In the present double-blind placebo-controlled study the effect of cisapride on functional dyspepsia was evaluated in patients with and without histological gastritis. Patients with functional dyspepsia and whose symptoms persisted after a 2 week run-in period with antacid treatment were randomized to receive cisapride (10 mg) or matching placebo three times daily for 4 weeks. Symptoms of epigastric pain, bloating, nausea, belching, early satiety and heartburn were graded on a four-point scale based on patients' feedback and diary card recording. A global response was also formulated by the investigators. One hundred and four patients entered the study and 76 completed the trial, comprising 36 patients with histological gastritis and 40 patients without gastritis. Symptom scores in both gastritis and non-gastritis groups were significantly improved by both cisapride and placebo; however, the improvement was not statistically different between the two treatment groups. Cisapride produced a good or better global response in 58% of subjects with histological gastritis and in 53% of subjects without gastritis compared with 47% and 52%, respectively, of patients on placebo; this difference was not statistically significant. Gastric histology did not influence the effect of cisapride on the symptoms of functional dyspepsia.

Introduction: Pharyngeal High Resolution Manometry (HRM) has been increasingly used in research studies. The utility of this technique for clinical purposes requires a better understanding of the effects of variables on the recorded pressure signature. Some of these variables such as neck position and volume of swallowed material may not have appreciable effect on esophageal pressure measurements but could affect the pharynx significantly. Therefore, our AIM was to determine the effect of the bolus volume, several neck positions, and posture on the pharyngeal and Upper Esophageal Sphincter (UES)pressure phenomenon using HRM technique. Methods: We studied 16 healthy young volunteers (8 F, age 20-30 years) with HRM in four neck positions (neck neutral, neck 15" extension, neck 30° and 45° flexion) and 2 body postures (sitting and supine), four volumes (dry and 5 ml, 10 ml and 20 ml). Each swallow volume was repeated three times. We measured amplitude (mmHg) duration (s) and velocity (cm/s). Results: A total of 1536 swallows were evaluated. Pharyngeal pressure phenomenon exhibited larger duration in the proximal pharynx compared to distal, while they exhibited higher amplitude in the distal pharynx compared to the proximal pharynx but not velopharyngeal region(P7-P6) (figure 1a and 1b). These parameters were not affected by posture, neck position or volume of swallowed liquid. Intrabolus hypopharyngeal pressure (IBP) increased with increased swallowed volume significantly (P,0.05). There was no effect by posture or neck position on the IBP. Resting UES pressure was not affected by the posture, however it showed significant change due to neck position P,0.05 (Table) ConclusionDuring pharyngeal HRM, neck position or posture has no appreciable effect on recorded pharyngeal peristalsis; however it affects the UES pressure significantly. This effect needs to be considered during pharyngeal HRM. Table. Effect of neck position on pharyngo-UES HRM variables

SUMMARY Background: Polyunsaturated phosphatidyl choline is a preparation often advocated for diseases of the liver. Methods: In a randomized open controlled trial, a preparation of polyunsaturated phosphatidyl choline, at a dose of 900 mg orally daily, was given to 22 patients with acute viral hepatitis. A control group of 25 patients was not treated. Results: Serial serum bilirubin and alanine amino transferase levels were measured up to 12 weeks. The falls in their levels after 2 and 5 weeks, and the lengths of time to their normalization, were not significantly different in the treated group compared to the control group. Conclusion: The results indicated that polyunsaturated phosphatidyl choline had no beneficial effect on the course of acute viral hepatitis.

Background Based on limited studies, it has been suggested that there is a lower prevalence of IBS among Asians and that there is male predominance in patients consulting for IBS. On the other hand, we have previously reported that in our hospital based clinic the prevalence and demography of IBS are similar to those of western series. Aim To study the epidemiology of IBS in an urban Asian population. Method A validated bowel symptom questionnaire was administered by trained interviewers first to a proportional age-, sex- and race-stratified random sample of 3000 residents in Singapore. IBS was defined using the Rome II criteria. Results In the community survey, the response rate was 78.2% (n = 2276, 1143 males and 1133 females). The age, sex and racial distribution of our respondents were similar to the general population and there was no significant difference between respondents and nonrespondents by type of household. The prevalence of IBS was 12.2%. The prevalence of IBS was higher in women than men (14.1 vs. 10.3%, P = 0.006), the younger age group (13.8% in those aged 40 years or less vs. 10.8% in those aged more than 40 years, P = 0.034). IBS subjects appeared to be more prone to abdominal surgery 7.2% IBS subjects vs. 2.9% non-IBS subjects, P = 0.0004. The predominant bowel habits among community IBS subjects were constipation 47.1%, diarrhoea 44.4%. There was no difference in prevalence of IBS among different educational background. Conclusion The prevalence and demography of IBS in our Asian urban society is similar to the west with higher prevalence among women and younger age groups.