Factor Analysis of the Rome IV Criteria for Major Disorders of Gut-Brain Interaction (DGBI) Globally and Across Geographical, Sex, and Age Groups.

BACKGROUND & AIMS: The Rome criteria are widely accepted for diagnosing disorders of gut-brain interaction, but their global applicability has been debated. This study aimed to evaluate the validity of the Rome IV criteria by factor analysis globally, across geographical regions, by sex, and by age groups. METHODS: Data were collected in 26 countries using the Rome IV questionnaire. Forty-nine ordinal variables were used in exploratory factor analysis (EFA) to identify clusters of inter-correlated variables (factors) within the data set. Confirmatory factor analysis with predefined factors of the disorders of gut-brain interaction was compared with the factors in the EFA. Analyses were performed globally, for each geographical region (North and Latin America, Western and Eastern Europe, Middle East, Asia), sex, and age groups (18-34, 35-49, 50-64, ≥65). RESULTS: A total of 54,127 people were included. The EFA identified 10 factors accounting for 57% of the variance: irritable bowel syndrome, constipation, diarrhea, upper gastrointestinal symptoms, globus, regurgitation/retching, chest pain, nausea/vomiting, and 2 right upper quadrant pain factors. Most factors had close correspondence to a Rome IV criteria diagnosis, but notably, functional dysphagia and heartburn symptoms were often included in the same factor and/or in upper gastrointestinal symptoms. Most factors were consistent across geographical regions, sex, and age groups, and compatible to the global results. All prespecified factors in the confirmatory analysis had a loading ≥0.4, indicating validity of the Rome IV criteria. CONCLUSIONS: The results indicate that the Rome IV criteria for irritable bowel syndrome, functional dyspepsia, functional constipation, globus, and biliary pain are globally valid and represent universal diagnostic entities that are similar across sex and age groups.

Global Prevalence of Psychological Distress and Comorbidity With Disorders of Gut-Brain Interactions.

INTRODUCTION: This study focused on defining the global prevalence of clinically relevant levels of psychological distress and somatic symptoms and the prevalence of coexistence between these symptoms and disorders of gut-brain interaction (DGBI). We also analyzed how clinically relevant psychological distress and somatic symptoms and coexistent DGBI are associated with health-related outcomes. METHODS: We included a representative sample of 54,127 adult participants (49.1% women; mean age of 44.3 years) from 26 countries worldwide. Participants completed an Internet survey (the Rome Foundation Global Epidemiology Study) with validated self-report questionnaires. RESULTS: Clinically relevant psychological distress and/or somatic symptom severity was reported by 37.5% of the sample. These participants had 4.45 times higher odds to have at least one DGBI than individuals without psychological distress and/or somatic symptoms. Compared with participants with psychological distress and/or somatic symptoms with vs without DGBI, participants with a DGBI reported increased healthcare and medication utilization (with OR from 1.6 to 2.8). Coexistent DGBI in participants with psychological distress and/or somatic symptoms was the variable most strongly associated with reduced mental (ß = -0.77; confidence interval [-0.86 to -0.68]) and physical (ß = -1.17; confidence interval [-1.24 to -1.10]) quality of life. DISCUSSION: This global study shows that psychological distress, somatic symptoms, and DGBI are very common and frequently overlap. The coexistence between psychological distress/somatic symptoms and DGBI seems to be especially detrimental to quality of life and healthcare utilization. Individuals with psychological distress/somatic symptoms and DGBI coexistence seem to be a group vulnerable to psychosocial problems that should be studied further and would likely benefit from psychological/psychiatric interventions.

Global Prevalence and Impact of Rumination Syndrome.

BACKGROUND & AIMS: Rumination syndrome is a Disorder of Gut-Brain Interaction (DGBI) of unknown etiology. We aimed to assess its global prevalence and potential associations with other medical conditions. METHODS: Data were collected via the Internet in 26 countries. Subjects were evenly distributed by country, sex, and age groups and were invited for a "health survey" using the Rome IV diagnostic questionnaire and a supplementary questionnaire addressing factors potentially associated with DGBI. RESULTS: In all, 54,127 subjects completed the survey (51% male; mean age, 44.3 years). The overall prevalence of rumination syndrome was 3.1% (95% confidence interval [CI], 3.0-3.3%). It was highest in Brazil (5.5% CI, 4.5-6.5) and lowest in Singapore (1.7% CI, 1.1-2.2). The mean age of people with rumination syndrome was 44.5 years (standard deviation, 15.6) and it was more common in females (54.5% vs 45.5%). Factors independently associated with rumination syndrome were depression (odds ratio [OR], 1.46), anxiety (OR, 1.8), body mass index (OR, 1.04), and female sex (OR, 1.19). Subjects with multiple DGBI were at increased risk of having rumination syndrome, with the highest risk in subjects with 4 gastrointestinal regions with DGBI (OR, 15.9 compared with none). Quality of life (QoL) was lower in subjects with rumination syndrome compared with the rest of the cohort (PROMIS-10 score: physical QoL mean 12.9 vs 14.5; mental QoL mean 12.0 vs 13.6). CONCLUSIONS: The prevalence of rumination syndrome is higher than reported in most previous population studies and is likely underdiagnosed in clinical practice. Awareness of rumination syndrome should be raised among clinicians to improve care for these patients.

Warfarin Is Associated With Higher Rates of Upper But Not Lower Gastrointestinal Bleeding Compared with Direct Oral Anticoagulants: A Population-Based Propensity-Weighted Cohort Study.

BACKGROUND AND AIMS: While overall gastrointestinal bleeding (GIB) rates have been extensively compared between warfarin and direct oral anticoagulants (DOACs), it is still unclear whether upper and lower GIB rates differ between these types of drugs. This study aimed to compare upper and lower GIB rates between warfarin and DOACs in a nationwide cohort. METHODS: Data on all patients in Iceland who received a prescription for oral anticoagulation from 2014 to 2019 were collected and their personal identification numbers linked to the electronic medical record system of the National University Hospital of Iceland and the 4 regional hospitals in Iceland. Inverse probability weighting was used to yield balanced study groups and rates of overall, major, upper, and lower GIB were compared using Cox regression. All GIB events were manually confirmed by chart review. RESULTS: Warfarin was associated with higher rates of upper GIB (1.7 events per 100 person-years vs 0.8 events per 100 person-years; hazard ratio [HR], 2.12; 95% confidence interval [CI], 1.26-3.59) but similar rates of lower GIB compared with DOACs. Specifically, warfarin was associated with higher rates of upper GIB compared with apixaban (HR, 2.63; 95% CI, 1.35-5.13), dabigatran (5.47; 95% CI, 1.87-16.05), and rivaroxaban (HR, 1.74; 95% CI, 1.00-3.05). Warfarin was associated with higher rates of major GIB compared with apixaban (2.3 events per 100 person-years vs 1.5 events per 100 person-years; HR, 1.79; 95% CI, 1.06-3.05), but otherwise overall and major GIB rates were similar in warfarin and DOAC users. CONCLUSIONS: Warfarin was associated with higher rates of upper but not overall or lower GIB compared with DOACs. Warfarin was associated with higher rates of major GIB compared with apixaban.

Global prevalence and burden of meal-related abdominal pain.

BACKGROUND: Patients with disorders of gut-brain interaction (DGBI) report meal intake to be associated with symptoms. DGBI patients with meal-related symptoms may have more severe symptoms overall and worse health outcomes, but this subgroup has not been well characterized. We aimed to describe the global prevalence of meal-related abdominal pain and characterize this subgroup. METHODS: The data analyzed originated from the Internet survey component of the population-based Rome Foundation Global Epidemiology Study, completed in 26 countries (n = 54,127). Adult subjects were asked whether they had abdominal pain and how often this was meal-related. Respondents were categorized into "no," "occasional," and "frequent" meal-related abdominal pain groups based on 0%, 10-40%, and ≥50% of the pain episodes being meal-related, respectively. DGBI diagnoses, frequency of other GI symptoms, psychological distress, non-GI somatic symptoms, quality of life, and healthcare utilization were compared between groups. Mixed linear and ordinal regression was used to assess independent associations between psychological distress, non-GI somatic symptoms, quality of life, other GI symptoms, and meal-related abdominal pain. RESULTS: Overall, 51.9% of the respondents reported abdominal pain in the last 3 months, and 11.0% belonged to the group with frequent meal-related abdominal pain, which included more females and younger subjects. DGBI diagnoses were more common in subjects with frequent meal-related abdominal pain, and the frequency of several GI symptoms was associated with having more frequent meal-related abdominal pain. Having meal-related abdominal pain more frequently was also associated with more severe psychological distress, non-GI somatic symptoms, and a poorer quality of life. The group with frequent meal-related abdominal pain also more often consulted a doctor for bowel problems compared to the other groups of meal-related abdominal pain. CONCLUSION: Reporting frequent meal-related abdominal pain is common across the globe and associated with other GI and non-GI somatic symptoms, psychological distress, healthcare utilization, and a poorer quality of life. Individuals who frequently experience meal-related abdominal pain also more frequently fulfill the diagnostic criteria for DGBI. Assessing meal-related symptoms in all DGBI patients could be of major importance to improve and individualize symptom management.

Warfarin is associated with higher rates of epistaxis compared to direct oral anticoagulants: A nationwide propensity score-weighted study.

BACKGROUND: Although epistaxis is one of the most common side effects of oral anticoagulation, it is unclear whether epistaxis rates vary between different oral anticoagulants (OAC). OBJECTIVE: To compare rates of clinically relevant epistaxis between OAC. METHODS: Epistaxis event rates were compared between new users of apixaban, dabigatran, rivaroxaban, and warfarin in a nationwide population-based cohort study over a 5-year study period, 2014-2019. Data was collected from the Icelandic Medicine Registry and the five major hospitals in Iceland. Inverse probability weighting (IPW) was used to yield balanced baseline characteristics, and epistaxis rates were compared using Kaplan-Meier survival estimates and Cox regression. RESULTS: During the study period, 2098 patients received apixaban, 474 dabigatran, 3106 rivaroxaban, and 1403 warfarin. In total, 93 patients presented with clinically relevant epistaxis, including 11 (12%) major epistaxis events and one fatal epistaxis episode. Furthermore, seven patients (9%) with non-major epistaxis later presented with major bleeding during the follow-up period. Warfarin use was associated with higher rates of epistaxis compared to apixaban (2.2 events per 100-person years (events/100-py) vs. 0.6 events/100-py, hazard ratio [HR] 4.22, 95% confidence interval [CI] 2.08-8.59, p < 0.001), rivaroxaban (2.2 events/100-py vs. 1.0 events/100-py, HR 2.26, 95% CI 1.28-4.01, p = 0.005), and dabigatran (2.2 events/100-py vs. no events, HR n/a, p < 0.001). CONCLUSION: Warfarin treatment was associated with higher rates of clinically relevant epistaxis compared to direct oral anticoagulants.

Causes of gastrointestinal bleeding in oral anticoagulant users compared to non-users in a population-based study.

BACKGROUND/AIMS: Causes of gastrointestinal bleeding (GIB) in patients on oral anticoagulants (OACs) are not well established. The aims of the study were to compare the causes of GIB in patients on OACs and those not on OAC therapy. METHODS: A nationwide study of all GIB events in patients on OACs in Iceland from 2014-2019 was conducted. Bleeding events were obtained through ICD-10 codes and review of endoscopy databases, confirmed by review of medical records. For comparison, patients not on OACs from previous Icelandic population-based studies were used. RESULTS: Among 752 GIB events in 12,005 patients on OACs, 273 (1.9%) had verified upper and 391 (2.7%) had verified lower GIB. For lower GIB, multivariate analysis showed that OAC users were more likely to have colonic polyps (OR 6.6, 95% CI: 2.4 - 17.8, p < .001) or colorectal cancer (OR 3.7, 95% CI: 2.0 - 7.0, p < .001) but less likely to have ischemic colitis (OR 0.11, 95% CI: 0.04 - 0.26, p < .001). For upper GIB, bleeding from mucosal erosions (OR 4.0 95% CI: 2.5 - 7.9, p < .001) and angiodysplasia (OR 3.6, 95%CI: 1.5 - 8.6, p = .003) were more common in OAC users. CONCLUSIONS: A high proportion of GIB caused by colonic polyps and colorectal cancer among OAC patients indicates that OACs treatment may facilitate cancer diagnosis. The low proportion of ischemic colitis among those on OACs suggests that OACs provide a protective effect against ischemic colitis. OACs seem to increase the bleeding from angiodysplasia and mucosal erosive disease.

Rivaroxaban Is Associated With Higher Rates of Gastrointestinal Bleeding Than Other Direct Oral Anticoagulants : A Nationwide Propensity Score-Weighted Study.

BACKGROUND: Gastrointestinal bleeding (GIB) rates for direct oral anticoagulants (DOACs) and warfarin have been extensively compared. However, population-based studies comparing GIB rates among different DOACs are limited. OBJECTIVE: To compare rates of GIB among apixaban, dabigatran, and rivaroxaban. DESIGN: Nationwide population-based cohort study. SETTING: Landspítali-The National University Hospital of Iceland and the 4 regional hospitals in Iceland. PATIENTS: New users of apixaban, dabigatran, and rivaroxaban from 2014 to 2019. MEASUREMENTS: Rates of GIB were compared using inverse probability weighting, Kaplan-Meier survival estimates, and Cox regression. RESULTS: In total, 2157 patients receiving apixaban, 494 patients receiving dabigatran, and 3217 patients receiving rivaroxaban were compared. For all patients, rivaroxaban had higher overall rates of GIB (3.2 vs. 2.5 events per 100 person-years; hazard ratio [HR], 1.42 [95% CI, 1.04 to 1.93]) and major GIB (1.9 vs. 1.4 events per 100 person-years; HR, 1.50 [CI, 1.00 to 2.24]) compared with apixaban. Rivaroxaban also had higher GIB rates than dabigatran, with similar point estimates, although the CIs were wider and included the possibility of a null effect. When only patients with atrial fibrillation were included, rivaroxaban was associated with higher rates of overall GIB than apixaban (HR, 1.40 [CI, 1.01 to 1.94]) or dabigatran (HR, 2.04 [CI, 1.17 to 3.55]). Dabigatran was associated with lower rates of upper GIB than rivaroxaban in both analyses. LIMITATIONS: Unmeasured confounding and small subgroup analyses. CONCLUSION: Rivaroxaban was associated with higher GIB rates than apixaban and dabigatran regardless of treatment indication. PRIMARY FUNDING SOURCE: Icelandic Centre for Research and Landspítali-The National University Hospital of Iceland.

Acute upper gastrointestinal bleeding: a population-based, five-year follow-up study.

OBJECTIVE: Data on long-term rebleeding risk and mortality in acute upper gastrointestinal bleeding (AUGIB) patients are scarce and comparison to controls are lacking. Aimsof the study were to assess long-term prognosis of AUGIB patients and compare to controls. METHODS: A population-based retrospective case-control study conducted at the National University Hospital of Iceland and included all patients who underwent endoscopy in 2010-2011. AUGIB was defined as haematemesis or coffee ground vomiting leading to hospitalization or occurring in a hospitalized patient. Controls underwent endoscopy in 2010-2011, matched for sex/age. Rebleeding was defined as AUGIB >14 days up to five years after index bleeding. RESULTS: Overall, 303 patients had AUGIB, mean age 67 (±18), controls66 years (±19), females, 51 and 46%, respectively. The five-year rebleeding rate for AUGIB patients was 13% (95%CI 9-17%), higher than the rate of bleeding events in controls, 3% (95%CI 1-5%; log-rank <0.001), hazard ratio (HR) 6.0 (95%CI 2.4-15) when correcting for comorbidities, NSAID's, PPI's and antithrombotics. The mortality of AUGIB patients at end of follow-up was higher when compared to controls, 39% (95%CI 49-33%) vs. 26% (95%CI 30-21%), log-rank <0.001, comorbidity-adjusted HR 1.4 (1.1-1.9). A subanalysis of non-variceal AUGIB yielded similar results in regard to rebleeding and mortality rates. CONCLUSIONS: AUGIB patients were at 6-fold risk of rebleeding compared to bleeding events in controls at five years of follow-up. Five-year mortality was higher in AUGIB patients when compared to controls even when correcting for age and comorbidities, suggesting that an episode of AUGIB indicates serious frailty.

Acute gastrointestinal bleeding among patients on antiplatelet and anticoagulant therapy after percutaneous coronary intervention.

BACKGROUND: Patients undergoing percutaneous coronary intervention (PCI) require dual antiplatelet therapy and some require additional anticoagulation. We aimed to investigate the incidence of acute gastrointestinal bleeding (AGIB) among PCI patients receiving antiplatelet and anticoagulant therapy. METHODS: A population-based study that included all patients undergoing PCI during 2008-2016 in Iceland. Data from the Icelandic Medicines Registry were obtained on all outpatient prescriptions 1 year after first PCI. Patients receiving single or dual-antiplatelet therapy with or without anticoagulation cotherapy were analyzed. Rehospitalization for AGIB and endoscopic data were obtained within the 12-month follow-up period. RESULTS: A total of 5166 patients (male 75%) underwent PCI during the study period. The incidence of AGIB was 1% (54/5166) per year. The mean age among non-bleeders 65 (±11) years was lower than among bleeders 69 (±9) years (p = .002). The proportion of acute upper GIB (AUGIB) was 56%, whereas lower GIB occurred in 44%. Overall, 41% with AUGIB had PPIs compared to 39% of non-bleeders (NS). The incidence of AGIB among patients on single antiplatelet therapy combined with an anticoagulant was 2.5% compared to 0.9% among those on single antiplatelet treatment alone (p = .028). The number needed to harm (NNH) for treatment with single antiplatelet therapy and anticoagulant therapy compared to single antiplatelet therapy was 62 but no deaths related to AGIB. CONCLUSIONS: The 1-year incidence of AGIB was low with no mortality. Bleeding risk was found to be higher among patients on single antiplatelet therapy combined with anticoagulant therapy compared to patients on single antiplatelet therapy alone.

Increased incidence of autoimmune hepatitis is associated with wider use of biological drugs.

BACKGROUND & AIMS: Population-based studies on the epidemiology of autoimmune hepatitis (AIH) are scarce. Drug-induced AIH (DIAIH) is increasingly recognized in association with immunomodulatory therapy. We aimed to determine the incidence, prevalence and natural history of AIH in a population-based setting. METHODS: We collected data of new diagnosis of AIH in Iceland from 2006 to 2015. Cases were identified through search of diagnostic codes and text search for AIH within electronical medical records of all hospitals in Iceland and through records of smooth muscle antibodies (SMA) test results by the only laboratory in the country analyzing SMA. Patients were included in the final analysis if they received the clinical diagnosis of AIH or were started on immunosuppressive therapy. RESULTS: The mean annual incidence of AIH in Iceland was 2.2 cases per 100 000 inhabitants. Point prevalence on 31 December 2015 was 27/100 000. The median age at diagnosis was 56 years and 86% of patients were of female gender. DIAIH was suspected in 13 of 71 patients (18%) of which eight cases were related to infliximab. Immunosuppressive treatment was started in all but two patients. At the end of follow-up (median 4.8 years) 66 of 71 (93%) patients were alive. CONCLUSION: The incidence and prevalence rates of AIH in Iceland are the highest reported so far in a population-based setting. Higher incidence can partly be explained by the increasing use of biological drugs. Immunosuppressive therapy was very effective in achieving remission and prognosis was favorable.

[Gastrointestinal bleeding in Iceland and in broader terms - a review].

Gastrointestinal bleeding is a common cause for presentation in the emergency room and hospitalization. The bleeding is usually categorized to upper or lower gastrointestinal bleeding. The purpose of this review article is to provide an overview of the incidence of gastrointestinal bleeding, etiology, risk factors, role of antithrombotics, evaluation of the severity of bleeding, therapy and outcome. Emphasis will be put on gastrointestinal bleeding within the Icelandic health care system but also in broader terms.

The SHA2PE score: a new score for lower gastrointestinal bleeding that predicts low-risk of hospital-based intervention.

OBJECTIVES: Lower gastrointestinal bleeding (LGIB) risk scores have mainly focused on identifying high-risk patients. A risk score aimed at predicting which patients will not require hospital-based intervention may reduce unnecessary hospital admissions. The aim of the current study was to develop such a risk score. MATERIAL AND METHODS: A retrospective, population-based study that included patients presenting to the emergency room (ER) with LGIB from 2010 to 2013. Hospital-based intervention was defined as blood transfusion, endoscopic hemostasis, arterial embolization or surgery. The study cohort was split into train (70%) and test (30%) data. Train data were used to produce a multiple logistic regression model and a risk score that was validated on the test data. RESULTS: Overall, 581 patients presented 625 times to the ER, mean age 61 (±22), males 49%. Of train data patients, 72% did not require hospital-based intervention. Independent predictors of low-risk patients (did not require hospital-based intervention) were systolic pressure ≥100mmHg (Odds ratio [OR] 4.9), hemoglobin >12g/dL (OR 103), hemoglobin 10.5-12.0g/dL (OR 19), no antiplatelets (OR 3.7), no anticoagulants (OR 2.2), pulse ≤100 (OR 2.9), and visible bleeding in the ER (OR 3.8). When validating the score on the test data, only 2% were wrongly predicted to be low-risk, the negative predictive value was 96% and the area under curve was 0.83. CONCLUSIONS: A new risk score has been developed for LGIB that may help identify low-risk patients in the ER that can be managed in an outpatient setting, thereby lowering unnecessary hospital admissions.

Incidence, diagnostic, treatment and outcome of patients diagnosed with cancer of the pancreas during 1986-2009: a population-based study.

OBJECTIVE: Limited data exist on the changes in the epidemiology of pancreatic cancer and outcomes over the last decades in population-based cohorts. We aimed to compare the incidence of pancreatic cancer, diagnostic, treatment and survival among patients diagnosed over the period 1986-2009. MATERIALS AND METHODS: A retrospective, nationwide, population-based study. All patients diagnosed with pancreatic cancer in Iceland in two periods, 1986-1997 (P1) and 1998-2009 (P2) were identified through the Icelandic Cancer Registry and relevant clinical information obtained from medical records. RESULTS: A total of 645 patients were identified, 296 in P1 and 349 in P2 (NS). The incidence during P1 was 6.8 per 100,000 inhabitants and 6.2 during P2 (NS). Among biopsy-proven cancers, adenocarcinoma was diagnosed in 89% of the cases in P1 and in P2 in 93% of the cases. Overall 38 (14%) in P1 underwent resection and 22 (7%) in P2 (p < .0004). Patients diagnosed in P2 had longer survival at 6 months (p = .015, log-rank test) and one year (p = .0206) after diagnosis. A total of 4/296 (1.4%) in P1 survived more than 5 years and 3/349 (0.9%) in P2 (NS). CONCLUSIONS: The incidence among patients with pancreatic cancer in Iceland did not show major changes during the last 20 years. Diagnostic approach has changed considerably demonstrating more patients that are not 'resectable'. Survival rate at 6 months and one year has improved over the last two decades whereas the 5-year prognosis has not improved.

The Association of Drugs With Severity and Specific Causes of Acute Lower Gastrointestinal Bleeding: A Prospective Study.

OBJECTIVES: Studies on the association of acute lower gastrointestinal bleeding (ALGIB) and drugs are scarce. We aimed to investigate the association of drugs and ALGIB, especially regarding specific causes of ALGIB, and their role in the severity of ALGIB. MATERIALS AND METHODS: The study was prospective and included all patients undergoing colonoscopy in 2010 and 2013 at the National University Hospital of Iceland. Use of nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin (LDA), and warfarin before ALGIB was registered. Clinically significant bleeding was defined as: hemoglobin <100 g/L, hemodynamic instability, blood transfusion, surgery, or death. RESULTS: Overall, 2392 patients underwent 2751 colonoscopies, of those, 325 (14%) had ALGIB, mean age 64 years (±20). The commonest diagnoses were diverticulosis (22%) and ischemic colitis (14%). In multivariate analysis, NSAIDs, LDA, and warfarin use was associated with ALGIB, odds ratio (OR) 3.3 [95% confidence interval (95% CI), 1.99-5.82], OR 1.5 (95% CI, 1.01-2.13), and OR 2.7 (95% CI, 1.61-4.57), respectively. Clinically significant bleeders were more likely than nonclinically significant bleeders to use NSAIDs or LDA+warfarin, OR 2.3 (95% CI, 1.26-3.76) and OR 33.0 (95% CI, 6.74-595), respectively. Patients with diverticular bleeding had greater odds than controls of NSAID, LDA, and warfarin use, OR 8.3 (95% CI, 3.8-18.3), OR 2.1 (95% CI, 1.15-3.67), and OR 2.6 (95% CI, 1.24-5.56), respectively. Patients with ischemic colitis were more likely than controls to use LDA, OR 2.3 (95% CI, 1.14-4.45). CONCLUSIONS: NSAIDs, LDA, and warfarin were associated with ALGIB and diverticular bleeding. These drugs may have a role in other etiologies of ALGIB and seem to increase the risk of clinically significant bleeding.

The outcome and role of drugs in patients with unexplained gastrointestinal bleeding.

OBJECTIVE: Studies on unexplained gastrointestinal bleeding (GIB) are lacking. We aimed to study the clinical outcomes of patients with unexplained GIB and to determine the incidence of obscure GIB. MATERIAL AND METHODS: A population-based study on all patients undergoing endoscopy at the National University Hospital of Iceland in 2010. Indications, results of endoscopies and drug history were prospectively registered with a follow-up of 3 years. A national pharmaceutical database containing prescription data was utilized. Patients were categorized into unexplained overt and occult GIB and obscure GIB. Patients undergoing endoscopy and without GIB acted as controls. RESULTS: Of 2471 patients undergoing endoscopy, 11% had unexplained GIB. Of those, 46% had unexplained overt GIB, 44% had unexplained occult GIB and 11% had obscure GIB. Multivariate analysis showed that patients with unexplained GIB and unexplained overt GIB had greater odds of NSAID use than controls, OR 1.8 (CI 1.03-3.03) and OR 2.0 (CI 1.01-3.77), respectively. Warfarin was strongly associated with all bleeder groups, OR 4-4.8. The incidence of obscure GIB was 10/100,000 inhabitants annually. Two (0.8%) patients were diagnosed with colon cancer 16 and 30 months after the index colonoscopy. Of patients with unexplained overt, unexplained occult GIB and controls, 5%, 6% and 3.5% (NS) had another overt bleeding episode, during the study period. CONCLUSIONS: NSAIDs and warfarin seem to play an important role in unexplained GIB. The incidence of obscure GIB is low and missed cancers are very rare. The probability of a repeat bleeding episode is similar to that of controls.

The risk of colorectal cancer after an attack of uncomplicated diverticulitis.

OBJECTIVE: According to clinical guidelines, a colonoscopy is recommended after an attack of diverticulitis in order to exclude colorectal cancer (CRC). This is based on studies prior to the use of computerized tomography (CT) for confirmation of the diagnosis. We aimed to investigate the findings of a subsequent colonoscopy after an attack of uncomplicated diverticulitis. MATERIAL AND METHODS: The study cohort consisted of all patients with the diagnosis of uncomplicated diverticulitis, who underwent a subsequent colonoscopy 6-8 weeks later during a 6-years period in the National University Hospital of Iceland. The diagnosis of diverticulitis was based on clinical symptoms verified with a CT of the abdomen. Relevant clinical information was obtained from medical records and from the Icelandic Cancer Registry. RESULTS: A total of 282 patients had uncomplicated diverticulitis and 199 patients underwent endoscopy. Two patients had CRC (0.7%), diagnosed with diverticulitis but did not recover clinically. All other patients recovered clinically. Colonic polyps were found in 33 of 195 (17%) cases. In 19/33 (58%) cases the histology demonstrated hyperplastic polyps, and in 13/33 (39%) adenoma with mild dysplasia. Only 1/33 (3%) of the colonic polyps were >1 cm in size. CONCLUSIONS: Among patients experiencing an attack of uncomplicated diverticulitis the frequency of CRC was equal to what might be expected compared to the average risk in the population. In these patients a routine colonoscopy in the absence of other clinical signs of CRC seems hardly necessary, if the clinical course is uneventful and the patient recovers.

Factors Associated With Abdominal Pain in Patients With Active and Quiescent Ulcerative Colitis: A Multicohort Study.

BACKGROUND: Abdominal pain can be an overlooked symptom in patients with ulcerative colitis (UC). AIMS: The aim of this study was to investigate the prevalence and factors associated with abdominal pain in active and quiescent UC. METHODS: Three study cohorts of adult UC patients were used. Cross-sectional cohorts I and II included 130 (46 active) and 288 (156 active) patients. Longitudinal cohort III included 83 patients with active disease at diagnosis that reached deep remission during follow-up. The Gastrointestinal Symptom Rating Scale was used to assess abdominal pain and other validated questionnaires to assess psychological distress, fatigue and quality of life (QoL). RESULTS: In the two cross-sectional cohorts, 63% and 58% of the active vs. 54% and 33% of the quiescent UC patients reported abdominal pain (both p ≤ 0.02). In the longitudinal cohort, 71% had abdominal pain at diagnosis vs. 46% when in remission (p < 0.001). In multivariable models, symptoms of anxiety were associated with higher abdominal pain levels in both cross-sectional cohorts (OR 1.75 [IQR 1.11-2.76] and OR 1.99 [1.45-2.73]), whereas in cohort II, active disease (OR 2.68 [1.61-4.45]) and female sex (OR 2.03 [1.21-3.41]) were also associated with pain. QoL was negatively correlated with higher levels of abdominal pain, both in active and quiescent disease. CONCLUSIONS: Abdominal pain in UC is prevalent and associated with lower QoL in both active and quiescent disease. Associated factors are active disease, female sex and psychological symptoms, especially anxiety. We suggest considering a holistic approach when treating UC patients with abdominal pain.

Symptom profiles compatible with disorders of gut-brain interaction (DGBI) in organic gastrointestinal diseases: A global population-based study.

BACKGROUND: Patients with organic gastrointestinal (GI) diseases and diabetes mellitus (DM) can have concomitant disorders of gut-brain interaction (DGBI). OBJECTIVE: This study aimed to compare the global prevalence of DGBI-compatible symptom profiles in adults with and without self-reported organic GI diseases or DM. METHODS: Data were collected in a population-based internet survey in 26 countries, the Rome Foundation Global Epidemiology Study (n = 54,127). Individuals were asked if they had been diagnosed by a doctor with gastroesophageal reflux disease, peptic ulcer, coeliac disease, inflammatory bowel disease (IBD), diverticulitis, GI cancer or DM. Individuals not reporting the organic diagnosis of interest were included in the reference group. DGBI-compatible symptom profiles were based on Rome IV diagnostic questions. Odds ratios (ORs [95% confidence interval]) were calculated using mixed logistic regression models. RESULTS: Having one of the investigated organic GI diseases was linked to having any DGBI-compatible symptom profile ranging from OR 1.64 [1.33, 2.02] in GI cancer to OR 3.22 [2.80, 3.69] in IBD. Those associations were stronger than for DM, OR 1.26 [1.18, 1.35]. Strong links between organic GI diseases and DGBI-compatible symptom profiles were seen for corresponding (e.g., IBD and bowel DGBI) and non-corresponding (e.g., IBD and esophageal DGBI) anatomical regions. The strongest link was seen between fecal incontinence and coeliac disease, OR 6.94 [4.95, 9.73]. After adjusting for confounding factors, associations diminished, but persisted. CONCLUSION: DGBI-compatible symptom profiles are more common in individuals with self-reported organic GI diseases and DM compared to the general population. The presence of these concomitant DGBIs should be considered in the management of organic (GI) diseases.