Diabetes distress and depression are independently associated with gastrointestinal symptoms in type 2 diabetes in Bangladesh.

BACKGROUND AND AIMS: Gastrointestinal (GI) symptoms, common in type 2 diabetes (T2D), are typically bothersome, socially embarrassing, and impact negatively on quality of life. They may also contribute to diabetes distress (DD), but this has never been formally evaluated. We aimed to investigate the relationships between GI symptoms, DD and depressive symptoms in a large cohort of individuals with T2D in Bangladesh. MATERIALS AND METHODS: 1406 unselected T2D individuals (female 58.8%; mean age 51.0 ± 12.5 years) from four diabetes clinics in Bangladesh completed validated questionnaires evaluating GI symptoms (PAGI-SYM), DD (DDS-17) and depressive symptoms (PHQ-9). RESULTS: 31.1% of participants reported GI symptoms (36.2% females, 23.7% males), while 51.1% had elevated DD and 37.8% depressive symptoms. GI symptoms exhibited independent relationships with both DD and depressive symptoms, and their likelihood was higher among those with DD (OR: 3.6 [2.2-5.6] and with depressive symptoms (OR: 5.9 [3.5-9.9]). CONCLUSIONS: GI symptoms are independently associated with both DD and depressive symptoms in people with T2D in Bangladesh.

Neonatal immune challenge influences the microbiota and behaviour in a sexually dimorphic manner.

There is comorbidity between anxiety disorders and gastrointestinal disorders, with both linked to adverse early life events. The microbiome gut-brain-axis, a bidirectional communication system, is plastic throughout the neonatal period and is a possible mediator of this relationship. Here, we used a well-established neonatal rodent immune activation model to investigate the long-term effect of neonatal lipopolysaccharide (LPS) exposure on adult behaviour and the relationship to microbiome composition. Wistar rats were injected with LPS (0.05 mg/kg) or saline (equivolume) on postnatal days 3 and 5. In adulthood, behavioural tests were performed to assess anxiety-like behaviour, and microbiota sequencing was performed on stool samples. There were distinctly different behavioural phenotypes for LPS-exposed males and females. LPS-exposed males displayed typical anxiety-like behaviours with significantly decreased social interaction (F(1,22) = 7.576, p = 0.009) and increased defecation relative to saline controls (F(1,23) = 8.623, p = 0.005). LPS-exposed females displayed a different behavioural phenotype with significantly increased social interaction (F(1,22) = 6.094, p = 0.018), and exploration (F(1,24) = 6.359, p = 0.015), compared to saline controls. With respect to microbiota profiling data, Bacteroidota was significantly increased for LPS-exposed females (F(1,14) = 4.931p = 0.035) and Proteobacteria was decreased for LPS-exposed rats of both sexes versus controls (F(1,30) = 4.923p = 0.035). Furthermore, alterations in predicted functional pathways for neurotransmitters in faeces were observed with a decrease in the relative abundance of D-glutamine and D-glutamate metabolism in LPS exposed females compared to control females (p < 0.05). This suggests that neonatal immune activation alters both later life behaviour and adult gut microbiota in sex-specific ways. These findings highlight the importance of sex in determining the impact of neonatal immune activation on social behaviour and the gut microbiota.

Optimal management of severe symptomatic gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a common disorder, and empirical proton pump inhibitor (PPI) treatment is often the first step of management; however, up to 40% of patients remain symptomatic despite PPI treatment. Refractory reflux refers to continued symptoms despite an adequate trial of PPI, and management remains challenging. The differential diagnosis is important; other oesophageal (e.g. eosinophilic oesophagitis) and gastroduodenal disorders (e.g. functional dyspepsia) should be ruled out, as this changes management. A combination of clinical assessment, endoscopic evaluation and in selected cases oesophageal function testing can help characterize patients with refractory reflux symptoms into oesophageal phenotypes so appropriate therapy can be more optimally targeted. Medical options then may include adding a H2 receptor antagonist, alginates, baclofen or antidepressant therapy, and there is emerging evidence for bile acid sequestrants and diaphragmatic breathing. The demonstration of a temporal association of symptoms with reflux events on pH-impedance testing (reflux hypersensitivity) serves to focus the management on modulating oesophageal perception and reducing the reflux burden, or identifies those with no obvious pathophysiologic abnormalities (functional heartburn). Anti-reflux surgery based on randomized controlled trial evidence has a role in reflux hypersensitivity or continued pathological acid reflux despite PPI in carefully considered, fully worked up cases that have failed medical therapy; approximately two of three cases will respond but there is a small risk of complications. In patients with persistent volume reflux despite medical therapy, given the lack of alternatives, anti-reflux surgery is a consideration. Promising newer approaches include endoscopic techniques. This review aims to summarize current diagnostic approaches and critically evaluates the evidence for the efficacy of available treatments.

Effects of Antidepressants on Gastric Function in Patients with Functional Dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is a highly prevalent functional bowel disorder. The effects of antidepressant therapy (ADTx) on gastric sensorimotor function in FD patients are poorly understood. AIMS: Determine whether FD and subtypes with abnormalities in gastric function respond differently to ADTx compared to those with normal physiology. METHODS: This multicenter, prospective trial randomized FD patients to 12 weeks of amitriptyline (AMI; 50 mg), escitalopram (ESC; 10 mg), or matching placebo. Demographics, symptoms, psychological distress, gastric emptying, and satiation were measured. Gastric accommodation (GA) using single-photon emission computed tomography imaging was performed in a subset of patients. An intent to treat analysis included all randomized subjects. The effect of treatment on gastric emptying was assessed using ANCOVA. A post hoc appraisal of the data was performed categorizing patients according to the Rome III subgrouping (PDS and EPS). RESULTS: In total, 292 subjects were randomized; mean age=44 yrs. 21% had delayed gastric emptying. Neither antidepressant altered gastric emptying, even in those with baseline delayed gastric emptying. GA increased with ADTx (P=0.02). Neither antidepressant affected the maximal-tolerated volume (MTV) of the nutrient drink test although aggregate symptom scores improved compared to placebo (P=0.04). Patients with the combined EPS-PDS subtype (48%) had a lower MTV on the nutrient drink test compared to the EPS group at baseline (P=0.02). Postprandial bloating improved with both AMI (P=0.03) and ESC (P=0.02). CONCLUSIONS: Amitriptyline (50 mg) improves FD symptoms but does not delay gastric emptying, even in patients with baseline delayed gastric emptying. GA improved with low-dose ADTx; the precise mechanism of action is unknown warranting further study.

A pragmatic comparative study of palliative care clinician's reports of the degree of shadowing visible on plain abdominal radiographs.

The assessment of constipation symptoms is based on history and physical examination. However, the experience is highly subjective perhaps explaining why palliative medicine doctors continue to use plain abdominal radiographs as part of routine assessment of constipation. Previous studies have demonstrated poor agreement between clinicians with this work in palliative care, limited further by disparity of clinicians' experience and training. The aim of this work was to explore whether there was less variation in the assessments of faecal shadowing made by more experienced clinicians compared to their less experienced colleagues. This pragmatic study was conducted across six palliative care services in Sydney (NSW, Australia). Doctors of varying clinical experience were asked to independently report their opinions of the amount of shadowing seen on 10 plain abdominal radiographs all taken from cancer patients who self-identified themselves as constipated. There were 46 doctors of varying clinical experience who participated including qualified specialists, doctors in specialist training and lastly, doctors in their second- and third post-graduate years. Poor agreement was seen between the faecal shadowing scores allocated by doctors of similar experience and training (Fleiss's kappa (FK): RMO 0.05; registrar 0.06; specialist 0.11). Further, when the levels of agreement between groups were considered, no statistically significant differences were observed. Although the doctors did not agree on the appearance of the film, the majority felt they were able to extrapolate patients' experiences from the radiograph's appearance. As it remains challenging in palliative care to objectively assess and diagnose constipation by history and imaging, uniform and objective assessment and diagnostic criteria are required. It is likely that any agreed criteria will include a combination of imaging and history. The results suggest the use of radiographs alone to diagnose and assess constipation in palliative care represents low value care.

Food and functional dyspepsia: a systematic review.

BACKGROUND: Functional dyspepsia (FD) is a debilitating functional gastrointestinal disorder characterised by early satiety, post-prandial fullness or epigastric pain related to meals, which affects up to 20% of western populations. A high dietary fat intake has been linked to FD and duodenal eosinophilia has been noted in FD. We hypothesised that an allergen such as wheat is a risk factor for FD and that withdrawal will improve symptoms of FD. We aimed to investigate the relationship between food and functional dyspepsia. METHODS: Sixteen out of 6451 studies identified in a database search of six databases met the inclusion criteria of studies examining the effect of nutrients, foods and food components in adults with FD or FD symptoms. RESULTS: Wheat-containing foods were implicated in FD symptom induction in six studies, four of which were not specifically investigating gluten and two that were gluten-specific, with the implementation of a gluten-free diet demonstrating a reduction in symptoms. Dietary fat was associated with FD in all three studies that specifically measured this association. Specific foods reported as inducing symptoms were high in either natural food chemicals, high in fermentable carbohydrates or high in wheat/gluten. Caffeine was associated with FD in four studies, although any association with alcohol was uncertain. CONCLUSIONS: Wheat and dietary fats may play key roles in the generation of FD symptoms and reduction or withdrawal eased symptoms. Randomised trials investigating the roles of gluten, FODMAPs (fermentable oligosaccharide, disaccharide, monosaccharide and polyols) and high fat ingestion and naturally occurring food chemicals in the generation of functional dyspepsia symptoms are warranted and further investigation of the mechanisms is now required.

The Validity of a New Structured Assessment of Gastrointestinal Symptoms Scale (SAGIS) for Evaluating Symptoms in the Clinical Setting.

BACKGROUND: The clinical assessments of patients with gastrointestinal symptoms can be time-consuming, and the symptoms captured during the consultation may be influenced by a variety of patient and non-patient factors. To facilitate standardized symptom assessment in the routine clinical setting, we developed the Structured Assessment of Gastrointestinal Symptom (SAGIS) instrument to precisely characterize symptoms in a routine clinical setting. AIMS: We aimed to validate SAGIS including its reliability, construct and discriminant validity, and utility in the clinical setting. METHODS: Development of the SAGIS consisted of initial interviews with patients referred for the diagnostic work-up of digestive symptoms and relevant complaints identified. The final instrument consisted of 22 items as well as questions on extra intestinal symptoms and was given to 1120 consecutive patients attending a gastroenterology clinic randomly split into derivation (n = 596) and validation datasets (n = 551). Discriminant validity along with test-retest reliability was assessed. The time taken to perform a clinical assessment with and without the SAGIS was recorded along with doctor satisfaction with this tool. RESULTS: Exploratory factor analysis conducted on the derivation sample suggested five symptom constructs labeled as abdominal pain/discomfort (seven items), gastroesophageal reflux disease/regurgitation symptoms (four items), nausea/vomiting (three items), diarrhea/incontinence (five items), and difficult defecation and constipation (2 items). Confirmatory factor analysis conducted on the validation sample supported the initially developed five-factor measurement model ([Formula: see text], p < 0.0001, χ 2/df = 4.6, CFI = 0.90, TLI = 0.88, RMSEA = 0.08). All symptom groups demonstrated differentiation between disease groups. The SAGIS was shown to be reliable over time and resulted in a 38% reduction of the time required for clinical assessment. CONCLUSIONS: The SAGIS instrument has excellent psychometric properties and supports the clinical assessment of and symptom-based categorization of patients with a wide spectrum of gastrointestinal symptoms.

Building a sustainable clinical academic workforce to meet the future healthcare needs of Australia and New Zealand: report from the first summit meeting.

The delivery of healthcare that meets the requirements for quality, safety and cost-effectiveness relies on a well-trained medical workforce, including clinical academics whose career includes a specific commitment to research, education and/or leadership. In 2011, the Medical Deans of Australia and New Zealand published a review on the clinical academic workforce and recommended the development of an integrated training pathway for clinical academics. A bi-national Summit on Clinical Academic Training was recently convened to bring together all relevant stakeholders to determine how best to do this. An important part understood the lessons learnt from the UK experience after 10 years since the introduction of an integrated training pathway. The outcome of the summit was to endorse strongly the recommendations of the medical deans. A steering committee has been established to identify further stakeholders, solicit more information from stakeholder organisations, convene a follow-up summit meeting in late 2015, recruit pilot host institutions and engage the government and future funders.

The brain--gut pathway in functional gastrointestinal disorders is bidirectional: a 12-year prospective population-based study.

OBJECTIVE: Psychological factors are known to be associated with functional gastrointestinal disorders (FGIDs) including irritable bowel syndrome (IBS) and functional dyspepsia (FD). No prospective studies have evaluated whether it is the brain (eg, via anxiety) that drives gut symptoms, or whether gut dysfunction precipitates the central nervous system features such as anxiety. In a 12-year longitudinal, prospective, population-based study, we aimed to determine the directionality of the brain-gut mechanism in FGIDs. DESIGN: Participants (n=1775) were a random population sample from Australia who responded to a survey on FGIDs in 1997 and agreed to be contacted for future research; 1002 completed the 12-year follow-up survey (response rate =60%), with 217, 82 and 45 people meeting Rome II for new onset FGIDs, IBS and FD, respectively. Anxiety and depression were measured using the Delusions Symptom States Inventory at baseline and follow-up. RESULTS: Among people free of a FGID at baseline, higher levels of anxiety (OR 1.11; 95% CI 1.03 to 1.19, p=0.006) but not depression at baseline was a significant independent predictor of developing new onset FGIDs 12 years later. Among people who did not have elevated levels of anxiety and depression at baseline, those with a FGID at baseline had significantly higher levels of anxiety and depression at follow-up (mean difference coefficient 0.76, p<0.001 and 0.30, p=0.01 for anxiety and depression, respectively). In IBS higher levels of anxiety and depression at baseline were predictive of IBS at follow-up, while only depression was predictive of FD at follow-up. CONCLUSIONS: The central nervous system and gut interact bidirectionally in FGIDs.

The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review.

INTRODUCTION: Probiotics may benefit irritable bowel syndrome (IBS) symptoms, but randomised controlled trials (RCTs) have been conflicting; therefore a systematic review was conducted. METHODS: MEDLINE (1966 to May 2008), EMBASE (1988 to May 2008) and the Cochrane Controlled Trials Register (2008) electronic databases were searched, as were abstracts from DDW (Digestive Diseases Week) and UEGW (United European Gastroenterology Week), and authors were contacted for extra information. Only parallel group RCTs with at least 1 week of treatment comparing probiotics with placebo or no treatment in adults with IBS according to any acceptable definition were included. Studies had to provide improvement in abdominal pain or global IBS symptoms as an outcome. Eligibility assessment and data extraction were performed by two independent researchers. Data were synthesised using relative risk (RR) of symptoms not improving for dichotomous data and standardised mean difference (SMD) for continuous data using random effects models. RESULTS: 19 RCTs (18 papers) in 1650 patients with IBS were identified. Trial quality was generally good, with nine reporting adequate methods of randomisation and six a method of concealment of allocation. There were 10 RCTs involving 918 patients providing outcomes as a dichotomous variable. Probiotics were statistically significantly better than placebo (RR of IBS not improving=0.71; 95% CI 0.57 to 0.88) with a number needed to treat (NNT)=4 (95% CI 3 to 12.5). There was significant heterogeneity (chi(2)=28.3, p=0.001, I(2)=68%) and possible funnel plot asymmetry. Fifteen trials assessing 1351 patients reported on improvement in IBS score as a continuous outcome (SMD=-0.34; 95% CI -0.60 to -0.07). There was statistically significant heterogeneity (chi(2)=67.04, p<0.001, I(2)=79%), but this was explained by one outlying trial. CONCLUSION: Probiotics appear to be efficacious in IBS, but the magnitude of benefit and the most effective species and strain are uncertain.

Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis.

OBJECTIVE: Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder. Evidence for treatment of the condition with antidepressants and psychological therapies is conflicting. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs). MEDLINE, EMBASE and the Cochrane Controlled Trials Register were searched (up to May 2008). SETTING: RCTs based in primary, secondary and tertiary care. PATIENTS: Adults with IBS. INTERVENTIONS: Antidepressants versus placebo, and psychological therapies versus control therapy or "usual management". MAIN OUTCOME MEASURES: Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, 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 571 citations. Thirty-two RCTs were eligible for inclusion: 19 compared psychological therapies with control therapy or "usual management", 12 compared antidepressants with placebo, and one compared both psychological therapy and antidepressants with placebo. Study quality was generally good for antidepressant but poor for psychological therapy trials. The RR of IBS symptoms persisting with antidepressants versus placebo was 0.66 (95% CI, 0.57 to 0.78), with similar treatment effects for both tricyclic antidepressants and selective serotonin reuptake inhibitors. The RR of symptoms persisting with psychological therapies was 0.67 (95% CI, 0.57 to 0.79). The NNT was 4 for both interventions. CONCLUSIONS: Antidepressants are effective in the treatment of IBS. There is less high-quality evidence for routine use of psychological therapies in IBS, but available data suggest these may be of comparable efficacy.

Associations among binge eating behavior patterns and gastrointestinal symptoms: a population-based study.

BACKGROUND: The psychological symptoms associated with binge eating disorder (BED) have been well documented. However, the physical symptoms associated with BED have not been explored. Gastrointestinal (GI) symptoms such as heartburn and diarrhea are more prevalent in obese adults, but the associations remain unexplained. Patients with bulimia have increased gastric capacity. The objective of the study was to examine if the severity of binge eating episodes would be associated with upper and lower GI symptoms. METHODS: Population-based survey of community residents through a mailed questionnaire measuring GI symptoms, frequency of binge eating episodes and physical activity level. The association of GI symptoms with frequency of binge eating episodes was assessed using logistic regression models adjusting for age, gender, body mass index (BMI) and physical activity level. RESULTS: In 4096 subjects, BED was present in 6.1%. After adjusting for BMI, age, gender, race, diabetes mellitus, socioeconomic status and physical activity level, BED was independently associated with the following upper GI symptoms: acid regurgitation (P<0.001), heartburn (P<0.001), dysphagia (P<0.001), bloating (P<0.001) and upper abdominal pain (P<0.001). BED was also associated with the following lower GI symptoms: diarrhea (P<0.001), urgency (P<0.001), constipation (P<0.01) and feeling of anal blockage (P=0.001). CONCLUSION: BED appears to be associated with the experience of both upper and lower GI symptoms in the general population, independent of the level of obesity. The relationship between increased GI symptoms and physiological responses to increased volume and calorie loads, nutritional selections and rapidity of food ingestion in individuals with BED deserves further study.

Rectal bleeding: epidemiology, associated risk factors, and health care seeking behaviour: a population-based study.

PURPOSE: Rectal bleeding is considered an important sign of colonic disease, particularly colorectal cancer. The epidemiology of rectal bleeding in the community is poorly understood. Moreover, there is little information as to whether individuals seek health care for this problem. This study aimed to determine the prevalence of rectal bleeding and levels of healthcare seeking amongst an Australian population. METHOD: A community sample of adults aged above 18 years of Penrith (a Sydney suburb representative of the Australian population) selected randomly from the electoral roll. The survey consisted of a self-administered questionnaire sent out to 440 residents stratified for equal numbers of men and women. RESULTS: The response rate was 77% (n = 338; mean age 46 years; SD: 16; range: 18-90; 55% women). Blood in the stools in the previous 12 months was reported by 18% (95% CI: 14-23). Colour of the blood in bowel movements was reported as bright (72%), dark (7%), bright and dark (10%), 11% did not know. Only 31% (n = 21/68) of respondents with rectal bleeding had visited a physician primarily about the presence of blood in the bowel movement within the previous 12 months. The majority (90%) who consulted about the presence of blood were aged between 30 and 60 years. Blood in the stools was independently associated with younger age (OR = 0.97, 95% CI: 0.95-0.99, P = 0.01), feelings of incomplete rectal evacuation (OR = 3.42, 95% CI: 1.66-7.08, P = 0.001), self-reported injury or tear (OR = 3.45, 95% CI: 1.53-7.69, P = 0.002), and surgery (OR = 2.70, 95% CI: 1.03-7.14, P = 0.04) to the perianal region. CONCLUSIONS: Rectal bleeding is common in the general population. Only one-third of those with rectal bleeding consults a physician about their condition. Rectal bleeding occurs in younger individuals, those who suffer from incomplete evacuation and among individuals who have had an injury, tear or surgery to the anus.

Itopride in functional dyspepsia: results of two phase III multicentre, randomised, double-blind, placebo-controlled trials.

BACKGROUND: Functional dyspepsia (FD) is a common disorder but there is currently little efficacious drug therapy. Itopride, a prokinetic approved in several countries, showed promising efficacy in FD in a phase IIb trial. The aim of this study was to test the efficacy and safety of this drug in FD. METHODS: Two similar placebo-controlled clinical trials were conducted (International and North America). Males and females, 18-65 years old, with a diagnosis of FD (Rome II) and the absence (by upper endoscopy) of any relevant structural disease were recruited. All were negative for Helicobacter pylori and, if present, heartburn could not exceed one episode per week. Following screening, patients were randomised to itopride 100 mg three times daily or identical placebo. The co-primary end points were: (1) global patient assessment (GPA) of efficacy; and (2) Leeds Dyspepsia Questionnaire (LDQ). Symptoms were evaluated at weeks 2, 4 and 8. Secondary measures of efficacy included Nepean Dyspepsia Index (NDI) quality of life. RESULTS: The GPA responder rates at week 8 on itopride versus placebo were similar in both trials (45.2% vs 45.6% and 37.8 vs 35.4%, respectively; p = NS). A significant benefit of itopride over placebo was observed for the LDQ responders in the International (62% vs 52.7%, p = 0.04) but not the North American trial (46.9% vs 44.8%). The safety and tolerability profile were comparable with placebo, with the exception of prolactin elevations, which occurred more frequently on itopride (18/579) than placebo (1/591). CONCLUSION: In this population with FD, itopride did not show a difference in symptom response from placebo.

Prevalence and risk factors for abdominal bloating and visible distention: a population-based study.

BACKGROUND: Abdominal bloating and visible distention are common yet poorly understood symptoms. Epidemiological data distinguishing visible distention from bloating are not available. We aimed to evaluate the prevalence and potential risk factors for abdominal bloating and visible distention separately in a representative US population, and their association with other functional gastrointestinal disorders (FGIDs). METHODS: The validated Talley Bowel Disease Questionnaire was mailed to a cohort selected at random from the population of Olmsted County, Minnesota. The complete medical records of responders were abstracted; 2259 subjects (53% females; mean age 62 years) provided bloating and distention data. RESULTS: The age and sex-adjusted (US White 2000) overall prevalence per 100 for bloating was 19.0 [95% confidence interval (CI), 16.9 to 21.2] vs 8.9 (95% CI, 7.2 to 10.6) for visible distention. Significantly increased odds for bloating alone and separately for distention (vs neither) were detected in females, and in those with higher overall Somatic Symptom Checklist (SSC) scores and higher scores of each individual SSC item. Further, females [odds ratio (OR), 1.5; 95% CI, 1.0 to 2.1], higher SSC score (OR, 1.4; 95% CI, 1.1 to 1.8), constipation-predominant irritable bowel syndrome (OR, 2.3; 95% CI, 1.3 to 4.1), dyspepsia (OR, 1.9; 95% CI, 1.1 to 3.2), and gastro-intestinal symptom complex overlap (OR, 1.7; 95% CI, 1.1 to 2.7) significantly increased odds for distention over bloating alone. CONCLUSIONS: Bloating and distention are common and have similar risk factors; somatisation probably plays a role.

Diagnostic utility of alarm features for colorectal cancer: systematic review and meta-analysis.

OBJECTIVE: Colorectal cancer is the second most common cause of cancer death in Europe and North America. Alarm features are used to prioritize access to urgent investigation, but there is little information concerning their utility in the diagnosis of colorectal cancer. METHODS: A systematic review and meta-analysis of the published literature was carried out to assess the diagnostic accuracy of alarm features in predicting colorectal cancer. Primary or secondary care-based studies in unselected cohorts of adult patients with lower gastrointestinal symptoms were identified by searching MEDLINE, EMBASE and CINAHL (up to October 2007). The main outcome measures were accuracy of alarm features or statistical models in predicting the presence of colorectal cancer after investigation. Data were pooled to estimate sensitivity, specificity, and positive and negative likelihood ratios. The quality of the included studies was assessed according to predefined criteria. RESULTS: Of 11 169 studies identified, 205 were retrieved for evaluation. Fifteen studies were eligible for inclusion, evaluating 19 443 patients, with a pooled prevalence of colorectal carcinoma of 6% (95% CI 5% to 8%). Pooled sensitivity of alarm features was poor (5% to 64%) but specificity was >95% for dark red rectal bleeding and abdominal mass, suggesting that the presence of either rules the diagnosis of colorectal cancer in. Statistical models had a sensitivity of 90%, but poor specificity. CONCLUSIONS: Most alarm features had poor sensitivity and specificity for the diagnosis of colorectal carcinoma, whilst statistical models performed better in terms of sensitivity. Future studies should examine the utility of dark red rectal bleeding and abdominal mass, and concentrate on maximising specificity when validating statistical models.

Biliary events and an increased risk of new onset irritable bowel syndrome: a population-based cohort study.

BACKGROUND: Prospective data are lacking to determine if irritable bowel syndrome (IBS) is a risk factor for cholecystectomy, or if biliary disease and cholecystectomy predisposes to the development of IBS. AIM: To test the hypothesis that IBS and biliary tract disease are associated. METHODS: Validated symptom surveys sent to cohorts of Olmsted County, MN, (1988-1994) with follow-up in 2003. Medical histories were reviewed to determine any 'biliary events' (defined by gallstones or cholecystectomy). Analyses examined were: (i) time to a biliary event post-initial survey and separately and (ii) risk of IBS (Rome II) in those with vs. without a prior biliary event. RESULTS: A total of 1908 eligible subjects were mailed a follow-up survey. For analysis (i) of the 726 without IBS at initial survey, 44 (6.1%) had biliary events during follow up, in contrast to 5 of 93 (5.4%) with IBS at initial survey (HR 0.8, 95% CI 0.3-2.1). For analysis (ii) of the 59 subjects with a biliary event at initial survey, 10 (17%) reported new IBS on the follow-up survey, while in 682 without a biliary event up to 1.5 years prior to the second survey, 58 (8.5%) reported IBS on follow-up (OR = 2.2, 95% CI 1.1-4.6, P = 0.03). CONCLUSION: There is an increased risk of new IBS in community subjects who have been diagnosed as having a biliary event.

The effect of short-term, low-dose tricyclic and tetracyclic antidepressant treatment on satiation, postnutrient load gastrointestinal symptoms and gastric emptying: a double-blind, randomized, placebo-controlled trial.

Antidepressants are commonly prescribed for patients with functional dyspepsia. However, the effect of tricyclic antidepressants on satiation and gastric emptying remains unclear, and there are no data for tetracyclic compounds. To compare the effects of nortriptyline (maximum dose: 50 mg daily) and mirtazapine (30 mg daily) vs placebo on gastric emptying, gastric satiation and postprandial symptoms after a nutrient load in healthy volunteers. Randomized, double-blind, placebo-controlled study evaluated gastric function before and after 14 days of nortriptyline (n = 13), mirtazapine (n = 13), or placebo (n = 14) in healthy volunteers. Validated methods were used to study gastric emptying ((13)C-octanoate) and satiation postnutrient drink test. The three arms were comparable with regard to age, gender, body mass index and hospital anxiety/depression scale. There were no statistically significant effects of mirtazapine or nortriptyline on gastric emptying compared to placebo (P = 0.34). Maximum tolerated volume was similar on drug and placebo (P = 0.56). Aggregate symptom score 30 min postmaximum tolerated volume after nutrient drink challenge on placebo was 132 (+/-21), vs 165 (+/-21) on mirtazapine, and 126 (+/-21) on nortriptyline 50 mg respectively (P = 0.28). Tricyclic and tetracyclic antidepressant agents do not appear to have significant effects on gastric motor or satiation postnutrient challenge in healthy individuals at the doses tested.

Do gastrointestinal symptoms fluctuate in the short-term perspective? The Kalixanda study.

BACKGROUND/AIM: Short-term fluctuation of gastrointestinal symptoms in the general population is largely unknown. We aimed to determine gastrointestinal symptom fluctuation in an random adult population using a validated questionnaire assessing gastrointestinal symptoms. METHODS: A representative sample (n = 2,860) of the population (n = 21,610, 20-81 years of age; mean age 50.4 years) in Northern Sweden was studied. The subjects were asked to complete the questionnaire on two occasions [mean 2.5 months (range 1-6)], firstly via mail and secondly at a visit to the clinic. An upper endoscopy was performed after the last assessment of symptoms. RESULTS: 2,122 individuals (74.2%) completed the initial questionnaire; 1,001 of these (mean age 54.1 years, 48.8 males) completed the second questionnaire. On the first occasion, 40% of the subjects were symptom-free (20.2%) or could not be classified according to their symptom pattern, of those with symptoms 39% reported troublesome reflux symptoms, 40% dyspeptic symptoms and 30% irritable bowel symptoms. Symptom overlap occurred in more than two thirds of the subjects. At the second visit 75% of the subjects who had reported dyspeptic complaints still reported such complaints. CONCLUSIONS: In this population-based study, gastrointestinal symptoms were common. Some symptom fluctuation occurred in the shorter term, but troublesome gastrointestinal complaints remained in approximately 90% of subjects over a 1-6-month period.