The population ≥65 years is rapidly increasing but remarkably little is known about the natural history of abdominal pain with aging.
To prospectively evaluate the natural history of abdominal pain (severity and frequency) in a US population, and evaluate potential risk factors (including somatization) for the onset and disappearance of abdominal pain with increasing age.
Between 1988 and 2004, valid self-report questionnaires that recorded gastrointestinal symptoms including severity and frequency of abdominal pain were mailed to randomly selected cohorts of community residents followed over time. This study identified all respondents who answered abdominal pain questions at an initial and follow-up survey.
1913 subjects were included (mean age in years at first survey: 48±12 (SD), mean age at second survey: 59±13 (SD); 53% female). The onset and disappearance rate of abdominal pain over the follow up were 14% (95% CI, 13,16) and 47% (43,50), respectively. The rates of increasing vs. decreasing abdominal pain score were 18% (16,20) vs. 22% (20,23), respectively. While younger age at initial survey was associated with onset of abdominal pain (vs. subjects without abdominal pain, [OR 0.9 (0.7,1.0)], older age at initial survey and times between surveys were associated with the disappearance of abdominal pain (vs. subjects with abdominal pain, [OR 1.2 (1.0,1.5)]. Female gender [OR 1.4 (1.0,2.1)], higher somatization scores and larger changes in somatization score [OR 5.3 (3.2,8.7)] were positively associated with the onset of abdominal pain.
Increasing age is associated with the disappearance of abdominal pain in the community.
AIM: To determine whether an increased number and duration of non-acid reflux events as measured using the multichannel intraluminal impedance pH (MII-pH) is linked to gastroparesis (GP).
METHODS: A case control study was conducted in which 42 patients undergoing clinical evaluation for continued symptoms of gastroesophageal reflux disease (both typical and atypical symptoms) despite acid suppression therapy. MII-pH technology was used over 24 h to detect reflux episodes and record patients’ symptoms. Parameters evaluated in patients with documented GP and controls without GP by scintigraphy included total, upright, and supine number of acid and non-acid reflux episodes (pH < 4 and pH > 4, respectively), the duration of acid and non-acid reflux in a 24-h period, and the number of reflux episodes lasting longer than 5 min.
RESULTS: No statistical difference was seen between the patients with GP and controls with respect to the total number or duration of acid reflux events, total number and duration of non-acid reflux events or the duration of longest reflux episodes. The number of non-acid reflux episodes with a pH > 7 was higher in subjects with GP than in controls. In addition, acid reflux episodes were more prolonged (lasting longer than 5 min) in the GP patients than in controls; however, these values did not reach statistical significance. Thirty-five patients had recorded symptoms during the 24 h study and of the 35 subjects, only 9% (n = 3) had a positive symptom association probability (SAP) for acid/non-acid reflux and 91% had a negative SAP.
CONCLUSION: The evaluation of patients with a documented history of GP did not show an association between GP and more frequent episodes of non-acid reflux based on MII-pH testing.
Gastroparesis; Non-acid gastroesophageal reflux; Acid gastroesophageal reflux; Multi-channel intraluminal impedance; Functional bowel disorder
Functional dyspepsia (FD) is a common problem affecting up to 10–25% of individuals. FD accounts for significant health care costs and affects quality of life but has no definitive treatment.
The Functional Dyspepsia Treatment Trial (FDTT) aims to test whether treatment with an antidepressant (amitriptyline or escitalopram) leads to improvement of symptoms in patients with moderate to severe FD.
The FDTT is an international multicenter, parallel group, randomized, double-blind, placebo-controlled trial to evaluate whether 12 weeks of treatment with escitalopram or amitriptyline improves FD symptoms compared to treatment with placebo. Secondly, it is hypothesized that acceleration of solid gastric emptying, reduction of postprandial satiation, and enhanced gastric volume change with a meal will be significant positive predictors of short- and long-term outcomes for those on antidepressants vs. placebo. The third aim is to examine whether polymorphisms of GNβ3 and serotonin reuptake transporter influence treatment outcomes in FD patients receiving a tricyclic antidepressant, selective serotonin reuptake inhibitor therapy, or placebo.
The FDTT enrollment began in 2006 and is scheduled to randomize 400 patients by the end of 2012 to receive an antidepressant or placebo for 12 weeks, with a 6-month post-treatment follow-up. The study incorporates multiple validated questionnaires, physiological testing, and specific genetic evaluations. The protocol was approved by participating centers' Institutional Review Boards and an independent Data Safety Monitoring Board was established for monitoring to ensure patient safety and a single interim review of the data in December 2010 (ClinicalTrials.gov number NCT00248651).
Amitriptyline; Antidepressive agents; Citalopram; Dyspepsia; Clinical trial; National Institute of Diabetes and Digestive and Kidney Diseases
Functional GI syndromes are known to be very prevalent but this may be associated with unrecognized medications use. We aimed to estimate the prevalence of PPI, antidepressant, and narcotic use in the general population, and evaluate the association between each medication and functional GI syndromes adjusting for potential confounders.
In 2008 and 2009, newly revised versions of a validated bowel disease questionnaire were mailed to a community based cohort (total mailed=8006) of Olmsted County, MN residents; 3831 returned the questionnaire (response rate=48.0%). Medication usage, specifically PPIs, narcotics, and antidepressants in the last year, was elicited via three separate questions on the questionnaire. The association between each medication and GI symptom complexes was assessed using multiple variable logistic regression models.
A total of 3515 of the respondents (92%) had complete data (mean age: 61±15; 54% female). The overall proportion reporting PPI use was 20% (95% CI: 19, 22), narcotic use 12% (95% CI: 11, 13), and antidepressant use 15% (95% CI: 14, 16). PPI use was significantly associated with IBS status (OR=1.4, 95% CI 1.1, 1.7) as well as with GERD (OR=3.5, 95% CI 2.7, 4.4) and dyspepsia (OR=2.0, 95% CI 1.5, 2.7). The association of PPI use with IBS was not explained by coexistent GERD or dyspepsia. Antidepressant use was significantly associated only with bloating (OR=1.6, 1.1, 2.2).
Some medications that may alter intestinal transit or bowel flora are commonly utilized by the general population, and PPI use appears to be linked to IBS.
Functional GI disorders; proton pump inhibitors; antidepressants; narcotics
Women with IBS frequently report chronic pelvic pain, however, it is still unanswered whether these are truly separate entities. IBS negatively impacts on quality of life, but the impact of IBS on sexual function is not clear.
We aimed to 1) describe the impact of IBS on sexual function, and 2) evaluate the association between pelvic pain and IBS, and in particular identify if there are unique characteristics of the overlap group.
The Talley Bowel Disease Questionnaire was mailed to an age-and gender-stratified random sample of 1,031 Olmsted County, Minnesota residents aged 30-64 years. Manning (at least 2 of 6 positive) and Rome criteria (Rome I and modified Rome III) were used to identify IBS. Pelvic pain was assessed by a single item. Somatization was assessed by the valid somatic symptom checklist.
Overall 648 (69%) of 935 eligible subjects responded (mean age 52 years, 52% female). Self-reported sexual dysfunction was rare (0.9%; 95% CI 0.3-2.0%). Among women, 20% (95% CI 16-24%) reported pain in the pelvic region; 40% of those with pelvic pain met IBS by Manning, or Rome criteria. IBS and pelvic pain occurred together more commonly than expected by chance (p<0.01). The overall somatization score (and specifically the depression and dizziness item scores) predicted IBS-pelvic pain overlap vs. either IBS alone or pelvic pain alone.
In a subset with pelvic pain, there is likely to be a common underlying psychological process (somatization) that explains the link to IBS.
IBS; pelvic pain; sexual dysfunction
It is known that the predisposition to human disease is a mixture of inherited susceptibility and acquired exposure to environmental factors. Understanding gastrointestinal disease has indicated that germline adenomatous polyposis coli mutations predispose with a 99% certainty to colorectal cancer, whereas squamous esophageal cancer is caused by a combination of environmental exposures (including alcohol consumption, cigarette smoke, ingestion of contaminated preserved food) and/or infection (specifically with human papilloma virus), in most cases. Until now, despite the reasonably strong evidence for genetic risk from monozygotic twin studies for gastroesophageal reflux disease (GERD), there have been no documented genetic targets in GERD. In this edition of the Journal, there is intriguing evidence that a common, single base-pair change in the secondary messenger gene GNβ3 (i.e., a single-nucleotide polymorphism) may be important, perhaps through promoting abnormal perception of visceral pain in the esophagus. Other works link this genetic factor to functional dyspepsia, and these exciting preliminary lines of evidence are reviewed.
The current health-care environment is demanding evidence-based medicine that relies on clinical trials as the basis for decisions. Clinician investigators are more often finding that they are personally responsible for coordinating large, multisite trials. We present strategies for successful implementation and management of multisite clinical trials and knowledge gained through an international, multisite randomized clinical trial. Topics include team composition, regulatory requirements, study organization and governance, communication strategies, recruitment and retention efforts, budget, technology transfer, and publication.
Psychosocial factors may drive people with irritable bowel syndrome (IBS) to seek health care, but whether psychological factors are causally linked to IBS is controversial. One hypothesis is that IBS is a heterogeneous syndrome comprising two distinct conditions, one psychological and the other biological. However, it is unclear how many people with IBS in the community have little somatization and minimal psychosocial distress. The aim of our study was to estimate the proportion of people with IBS in a representative US community, who have low levels of somatic and psychological symptoms.
The cohort comprised subjects from three randomly selected population studies from Olmsted County, Minnesota. All of them filled out a validated gastrointestinal (GI) symptom questionnaire, the Symptom Checklist-90-R (SCL-90-R), and the Somatic Symptom Checklist (SSC) comprising 11 somatic complaint items. Logistic regression models were used to evaluate the associations between somatic symptoms/psychosocial factors and IBS, adjusting for age and gender.
Of the 501 eligible subjects, 461 (92%) provided complete data (mean age = 56 years, 49% female). IBS (Rome II criteria) was associated with both higher SSC and Global Severity Index (GSI of SCL-90-R) scores. Among subjects with high (>75th percentile) SSC scores, 43% reported IBS vs. 10% of those with low (<25th percentile) SSC scores. Among those with high (>60) GSI scores, 23% reported IBS vs. 6% with low (<40) GSI scores. Specifically, none of the IBS subjects had both low SSC and low GSI scores.
Psychological factors and somatization are strongly associated with IBS in the community. However, IBS may not be related to low psychological distress and/or somatization.
Dyspepsia is common and the majority of patients have functional dyspepsia; however, potential risk factors are unclear with conflicting results in the literature. Although several risk factors have been evaluated previously, this knowledge has not lead to more effective management.
To assess potential novel risk factors for dyspepsia in both a cross sectional and a nested case control study among a randomly selected community based cohort.
A valid questionnaire was mailed to a random sample of Olmsted County, MN residents (n=659 responders; 133 had dyspepsia). In a nested case-control study, dyspeptic patients (n=52) and healthy controls (n=40) identified among community respondents completed further questionnaires on diet.
Independent risk factors for dyspepsia adjusted for age, sex, body mass index and anti-secretory therapy were a positive family history of abdominal pain (OR=4.7, 95% CI 1.5, 14.9, p=0.008) and indigestion (OR=3.4., 95% CI 1.0, 11.5, p=0.04) difficulty falling asleep (OR=8.2, 95% CI (2.2–31.5, p=0.002), poor sleep associated with worsening symptoms (OR=15.9, 95% CI (2.0–124.9, p=0.009) and a high somatic symptom checklist score (OR=5.6, 95% CI (1.5–20.7, p=0.01). Diet including total calories (kcalories/day) and total protein, carbohydrate and fat intake (grams/day) was not significantly associated with dyspepsia
Familial aggregation raises the possibility of a genetic component although shared environmental factors need to be considered. Sleep dysfunction and somatization suggests a primary psychological component.
Coeliac disease (CD) has been linked to gastro-oesophageal reflux disease (GORD) and eosinophilic oesophagitis (EoE), but population-based studies of the prevalence of CD in these conditions are lacking, that is, the aim of this study.
Materials and methods
An endoscopic study of 1000 randomly selected adults from the general population. CD was defined on the basis of positive serology in parallel with mucosal abnormalities of the small intestine. Any eosinophil infiltration of the oesophageal epithelium was defined as oesophageal eosinophilia and EoE was defined as having at least 15 eosinophils/high power field in biopsies from the distal oesophagus. We used Fisher’s exact test to compare the prevalence of GORD, oesophageal eosinophilia and EoE in subjects with CD vs. controls.
400 subjects (40%) had gastro-oesophageal reflux symptoms (GORS), 155 (15.5%) had erosive oesophagitis, 16 (1.6%) had Barrett’s oesophagus, 48 (4.8%) had oesophageal eosinophilia and 11 (1.1%) had EoE. CD was diagnosed in 8/400 (2.0%) individuals with GORS (vs. controls: 10/600 (1.7%), p=0.81), in 3/155 (1.9%) with erosive oesophagitis (vs. 15/845 controls (1.8%), p=0.75) and in 2/48 (4.2%) individuals with oesophageal eosinophilia (controls: 16/952 (1.7%) p=0.21), but in none of those 16 with Barrett’s oesophagus (vs. 18/984 controls (1.8%), p=1.0) or of the 11 individuals with EoE (controls: 18/989 (1.8%), p=1.0).
This population-based study found no increased risk of CD among individuals with GORD, oesophageal eosinophilia or EoE. CD screening of individuals with GORD or EoE of individuals with CD cannot be recommended.
Barrett’s oesophagus; coeliac disease; eosinophilic oesophagitis; erosive oesophagitis; gastro-oesophageal reflux disease
Functional dyspepsia (FD) is a highly prevalent but heterogeneous disorder in which multiple pathogenetic mechanisms are involved. Although there are many studies that have investigated various pathophysiologic mechanisms, the underlying casual pathways associated with FD remain obscure. The currently proposed pathophysiologic mechanisms associated with FD include genetic susceptibility, delayed as well as accelerated gastric emptying, visceral hypersensitivity to acid or mechanical distention, impaired gastric accommodation, abnormal fundic phasic contractions, abnormal antro-duodenal motility, acute and chronic infections, and psychosocial comorbidity. A greater understanding of the abnormalities underlying FD may lead to improved management. The aim of this editorial is to provide a critical overview of current pathophysiologic concepts in functional dyspepsia.
Functional dyspepsia; Gastric function; Pathophysiology
Population-based data on the epidemiology and outcomes of subjects with intestinal metaplasia of the gastroesophageal junction (IMGEJ) and Barrett's esophagus (BE) are limited. The objectives of this study were to (i) estimate the incidence of IMGEJ and BE diagnosed from clinically indicated endoscopy in Olmsted County, MN, over three decades (1976–2006) and prevalence as of 1 January 2007, (ii) compare baseline characteristics of subjects with IMGEJ and BE, and (iii) study the natural history and survival of both cohorts.
This was a population-based cohort study. The study setting was Olmsted County, MN. Patients with BE (columnar segment > 1 cm with intestinal metaplasia) and IMGEJ (intestinal metaplasia in biopsies from the gastroesophageal junction) from 1976 to 2006 in Olmsted County, MN, were identified using Rochester Epidemiology Project resources. Demographic and clinical data were abstracted from medical records and pathology confirmed by gastrointestinal pathologists. The association of baseline characteristics with overall and progression-free survival was assessed using proportional hazards regression models. Outcome measures were baseline characteristics and overall survival of subjects with IMGEJ compared to those with BE.
In all, 487 patients (401 with BE and 86 with IMGEJ) were identified and followed for a median interval of 7 (BE subjects) to 8 (IMGEJ subjects) years. Subjects with BE were older, heavier, reported reflux symptoms more often, and had higher prevalence of advanced neoplasia than those with IMGEJ. No patient with IMGEJ progressed to esophageal adenocarcinoma (EAC) in contrast to BE subjects who had a cumulative risk of progression of 7% at 10 years and increased risk of death from EAC (standardized mortality ratio 9.62). The overall survival of subjects with BE and IMGEJ did not differ from that expected in similar age- and sex-distributed white Minnesota populations.
Subjects with IMGEJ appear to have distinct clinical characteristics and substantially lower cancer progression risk compared to those with BE.
Prospective data are lacking to determine if IBS a risk factor for cholecystectomy, or if biliary disease and cholecystectomy predisposes to the development of IBS.
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: 1) time to a biliary event post initial survey and separately, 2) risk of IBS (Rome II) in those with vs. without a prior biliary event.
1908 eligible subjects mailed a follow-up survey. For aim 1) 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 aim 2) 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).
There is an increased risk of new IBS in community subjects who have been diagnosed as having a biliary event.
To extend earlier work1 that demonstrated that a HIPAA authorization form (HAF) introduced potential nonresponse bias (toward healthier respondents).
The sample frame from the earlier experiment was linked to administrative medical record data enabling the comparison of background and clinical characteristics of each set of respondents (HAF and No HAF) to the sample frame.
6,939 individuals residing in Olmsted County, Minnesota who were mailed a survey in September 2005 assessing recent gastrointestinal symptoms with an embedded HAF experiment comprise the study population.
The outcomes of interest were response status (survey returned vs. not) by HAF condition (randomized to receive HAF or not). Sociodemographic indicators included gender, age, and race. Health status was measured using the severity weighted Charlson Score and utilization was measured using ER visits, hospital admissions, clinic office visits, and procedures.
Younger and nonwhite residents were under-represented and those with more clinical office visits were over-represented in both conditions. Those responding to the survey in the HAF condition were significantly more likely to be in poor health compared to the population (27.3% with 2+ comorbidities vs. 24.6%, p=0.02).
The HAF did not influence the demographic composition of the respondents. However, counter to earlier findings based on self-reported health status1, responders in the HAF condition were slightly sicker than in the non-HAF condition. The HAF may introduce a small amount of measurement error by suppressing reports of poor health. Further, researchers should consider the impact of the HAF on resultant precision, respondent burden, and available financial resources.
survey methods; HIPAA; response rate; nonresponse bias
Irritable bowel syndrome (IBS) is one of the most common diagnoses made by gastroenterologists and primary care providers alike, and yet the underlying mechanism remains poorly understood. Family and twin studies suggest that IBS may have a genetic basis. Several candidate gene association studies have been performed, but thus far, they have failed to clearly identify an “IBS gene.” Epidemiological studies are needed to facilitate phenotype definition and identify relevant environment risk factors that will need to factor in gene and environment interactions in all future genetic studies. As genetic research in IBS is relatively nascent, much opportunity, as well as many challenges, exists in identifying the genes responsible for IBS.
Although direct medical costs for constipation-related medical visits are thought to be high, to date there have been no studies examining if longitudinal resource utilization is persistently elevated in children with constipation. Our aim was to estimate the incremental direct medical costs and types of health care utilization associated with constipation from childhood to early adulthood.
A nested case-control study was conducted to evaluate the incremental costs associated with constipation. The original sample consisted of 5,718 children in a population-based birth cohort who were born during 1976–1982 in Rochester, MN. The cases included individuals who presented to medical facilities with constipation. The controls were matched and randomly selected among all non-cases in the sample. Direct medical costs for cases and controls were collected from the time subjects were between 5–18 years of age or until the subject emigrated from the community.
We identified 250 cases with a diagnosis of constipation in the birth cohort. While the mean inpatient costs for cases were $9994 (95% CI=2538, 37201) compared to $2391 (95% CI=923, 7452) for controls (p=0.22) over the time period, the mean outpatient costs for cases were $13927 (95% CI=11325, 16525) compared to $3448 (95% CI=3771, 4621) for controls (p<0.001) over the same time period. The mean annual number emergency department visits for cases were 0.66 (95% CI=0.62, 0.70) compared to 0.34 (95% CI=0.32, 0.35) for controls (p<0.0001).
Individuals with constipation have higher medical care utilization. Outpatient costs and ER utilization were significantly greater for individuals with constipation from childhood to early adulthood.
Childhood constipation; Direct medical costs; Case-control study
While knowledge has accumulated regarding health care seeking in several functional gastrointestinal disorders (FGIDs), little is know about health care seeking in those with bloating and distention. We aimed to identify predictors of health care seeking for bloating and distention.
The validated Talley Bowel Disease Questionnaire was mailed to a cohort selected at random from the population of Olmsted County, Minnesota; 2,259 subjects (53% females; mean age 62 yr) answered questions about bloating and distention. The complete medical record of each respondent was reviewed. Logistic regression was used to compare consulting for bloating and distention to consulting for other GI symptoms, and non-consulters.
A total of 131 (6%) subjects in the community consulted a physician for bloating or distention. Older age (odds ratio(OR), 1.8; 95% confidence interval (CI): 1.5, 2.1), higher somatic symptom scores (OR, 2.0; CI: 1.4, 2.8), lower education level (OR, 2.7; CI: 1.2, 5.6), early satiety (OR, 2.0; CI: 1.1, 3.8), and abdominal pain (OR, 2.4; CI: 1.6, 3.7) were associated with people seeking health care for bloating or distention vs. non-consulters. Similarly, older age (OR, 1.4; CI: 1.2, 1.7), chronic constipation (OR, 2.0; CI: 1.2, 3.2) and visible distention (OR, 3.0; CI: 1.8, 4.9) had greater odds of presenting for bloating or distention compared to presenting for other GI symptoms; somatic symptoms were not a predictor (OR, 1.1; CI: 0.8, 1.5).
Factors that lead people to present for bloating and distention are similar to those for other GI symptoms visits; however, specific biologic rather than somatic features may predict visits for bloating and distention.
Large intestine Organ-based; Abdominal pain Topics; Epidemiology Topics; Motility Topics
Opioid prescription use is increasing. Narcotic bowel syndrome (NBS) refers to chronic abdominal pain aggravated by narcotic use. Despite increasing narcotic use, NBS may be under-recognized. The aim of this study was to assess whether gastrointestinal (GI) symptoms in the community are associated with chronic narcotic use and estimate the likely prevalence of NBS.
Validated self-report GI symptom questionnaires were mailed to 4,898 randomly selected people in the community. The medical charts of all respondents were reviewed to identify participants who had used narcotics and to determine whether they were taking an opioid for > 5 weeks for the treatment of chronic pain (malignant or nonmalignant). NBS was defined as abdominal pain developing in those taking chronic narcotics. The associations between GI symptoms and chronic narcotics use were assessed using logistic regression analysis.
A total of 2,913 respondents returned a completed questionnaire (overall response rate 59%, mean age 62, 52% female); 117 participants (4.1%, 95% confidence interval (CI): 3.3, 4.5) were taking narcotics. Five participants (0.17%; 95% CI: 0.06, 0.40%) met the criteria for NBS. Participants using narcotics had an increased use of laxatives (17 vs. 8% in those not using narcotics, P < 0.05). GI symptom reporting was more common in participants on narcotics, although the adjusted (for age, gender, somatic symptom complaints, and use of laxatives) odds ratios (ORs) were significantly increased only for frequent abdominal pain and stool frequency.
NBS may be relatively uncommon. Those on narcotics report additional GI symptoms (abdominal pain and stool frequency) and use more laxatives.
Smaller studies have evaluated SLC6A4 5-HTTLPR and GNβ3 825C>T polymorphisms in IBS, and interactions between 5-HTT LPR with life events have been reported in the psychiatric literature, but gene-environment studies in IBS are lacking.
To assess the association of two polymorphisms with IBS and age of onset; and to assess whether there are gene-environment interactions with IBS.
Outpatients with IBS and controls completed a validated questionnaire and provided blood for DNA. Comparisons of genotype/allele frequencies between cases and controls were performed with logistic regression. Linear regression was used to evaluate the association between the variants and age of onset. Environmental variables tested included abuse, parental alcohol abuse, parental psychiatric disorders, and gastrointestinal infections.
Genotyping was performed in 385 cases and 262 controls with median age of 50 yrs (range: 18.0–70.0) and 498 (77%) females. The IBS subtype distribution among cases was: 102 (26%) D-IBS, 40 (10%) C-IBS, 125 (32%) M-IBS, 118 (31%) other. No association was observed between IBS or age of onset and both variants. Significant interactions were observed between GI infection and the GNβ3 825T allele. For those reporting gastrointestinal infection, the OR for IBS was 3.9 (95%CI: 1.2–12.7) whereas the OR was 0.86 (95% CI: 0.65–1.13) for those without prior infection.
There was a significant interaction between the GNβ3 polymorphism and infection in the development of IBS, suggesting that its etiology is the result of a combination of specific genetic and environmental risk factors.
Irritable bowel syndrome; genes; genetics; infection
Background & Aims
Gastric injections of botulinum toxin A (BTA) have been reported to delay gastric emptying, increase satiation, and reduce body weight, but there are few data from randomized, placebo-controlled studies.
We enrolled 60 obese participants in a 24-week, double-blind, randomized, placebo-controlled, concealed allocation trial to compare the effects of gastric antral injections of BTA (100 U, 300 U, or 500 U) and saline placebo. The study was conducted at an outpatient clinical research unit. Participants were given one set of injections of BTA or placebo into the gastric antral muscularis propria, using endoscopic ultrasound guidance. Gastric emptying of solids (GES) was measured by scintigraphy; we also measured body weight, satiation (maximum tolerated volume in a caloric liquid drink test), calorie intake (by food frequency questionnaire), gastrointestinal symptoms, and psychologic aspects of eating behavior (by rating scale).
Compared with baseline values, 2 weeks after injections, the mean t1/2 for GES increased by 0.8, 14, 24, and 14 minutes among subjects given placebo, 100 U, 300 U, or 500 U of BTA, respectively (P=.24 overall, P=.04 for the group given 300 U vs placebo); 16 weeks after the injections, mean body weights were reduced by 2.2, 0.2, 2.3, and 3.0 kg in these groups, respectively. There were no statistically significant differences in mean body weight change, satiation volume, caloric intake, gastrointestinal symptoms, or psychological aspects of eating behavior among groups.
Gastric antral injections of BTA may delay gastric emptying at a dose of 300 U, but do not cause early satiety, altered eating behaviors, or loss of body weight. Clinicaltrials. gov identifier: NCT00976443
obesity; therapy; endoscopy; motility
To assess the association between Barrett’s esophagus (BE) and the Metabolic Syndrome in subjects with and without reflux symptoms and to determine if this association is reflux independent and metabolically driven.
Patients and Methods
BE cases and controls were residents of Olmsted County, MN (1999–2006). Two control groups (one with and one without symptoms of gastroesophageal reflux) were identified from a cohort of subjects who had responded to a validated GI symptom questionnaire. Cases and controls were individually matched by age, sex and duration of follow-up. Controls did not have a known diagnosis of BE. The association of the Metabolic Syndrome and its individual components with BE was assessed using univariate and multiple variable conditional logistic regression separately for each control group.
309 subjects were included (103 BE cases, 103 controls with reflux symptoms and 103 controls without reflux symptoms). 64% of cases, 47% of controls with reflux symptoms and 50% of controls without reflux symptoms had the Metabolic Syndrome. The Metabolic Syndrome was associated with a twofold increased risk of BE relative to subjects with (OR=2.00 (1.10, 3.65) p=0.02) and without (OR=1.90 (1.03, 3.60), p=0.04) reflux symptoms. This association was independent of smoking, alcohol consumption and BMI and remained robust with sensitivity analysis.
The Metabolic Syndrome is associated with BE independent of reflux symptoms. This may reflect a reflux independent pathway of BE pathogenesis.
Subjects with the Metabolic syndrome may be at higher risk for BE and esophageal adenocarcinoma.
arrett’s Esophagus; Metabolic syndrome; Obesity; Visceral fat; Screening; Esophageal Adenocarcinoma
The natural history of fecal incontinence (FI) in community subjects is uncertain and the onset rate is unknown. The aim of the study is to estimate the prevalence, new-onset rate, and risk factors for FI in community subjects.
A random sample of 2,400 community subjects aged ≥ 50 years was surveyed in 1993, using a validated questionnaire. Responders were recontacted in 2003. FI was defined as self-reported problems with leakage of stool. Onset rate was calculated as the proportion of subjects without FI who became new cases. Logistic regression models were constructed to identify predictive factors for developing FI and changes in bowel habit associated with the onset of FI.
Overall, 1,540 (64%) subjects responded to the initial survey, and 674 (44%) of them responded to the second survey a median of 9 (8.8 – 9.5) years later. The prevalence of FI in the first survey was 15.3% (13.4 – 17.3%). In the second survey, 37 reported incident FI; thus, the onset rate of FI was 7.0% (5.0 – 9.6) per 10 years. Predictive factors at baseline for the onset of FI were self-reported diarrhea (odds ratio (OR) = 3.8 (1.5, 9.4)), incomplete evacuation (OR = 3.4 (1.2, 9.8)), and pelvic radiation (OR = 5.1 (1.01, 25.9)). Development of urgency was the primary predictor among the set of predictors reflecting changes in bowel symptoms that were associated with the onset of FI (OR = 24.9 (10.6, 58.4)).
The onset rate of FI is approximately 7% per 10 years in community subjects aged ≥ 50 years. Prevention may be possible if bowel habit is appropriately managed in high-risk individuals.
Gastric injections of botulinum toxin A (BTA) may induce changes in gastric emptying and body weight, but results vary. BTA dose and depth of injection may affect efficacy. This study assessed changes in gastric emptying, satiation, symptoms, and body weight after endoscopic ultrasound (EUS)-guided injection of 100 or 300 U BTA into gastric antral muscularis propria of obese subjects.
Open label study of ten healthy, obese adults (age=29–49 years, body mass index=31–54 kg/m2) who received 100 U (n=4) or 300 U (n=6) BTA and were followed for 16 weeks. Measures included gastric emptying of solids (by scintigraphy), satiation (by maximum tolerated volume [MTV] during nutrient drink test), gastrointestinal symptoms (by the Gastrointestinal Symptom Rating Scale), caloric intake (by food frequency questionnaire), and body weight.
For the entire cohort, MTV decreased from 1,380 cc (range: 474–2,014) at baseline to 620 cc (range: 256–1,180) 2 weeks after BTA injection; decreases were statistically significant in the subjects receiving 300 U BTA (p=0.03). Average body weight loss was 4.9 (±6.3) kg after 16 weeks. Gastric emptying T1/2 was prolonged in the 300 U BTA group, but not significantly different from baseline (p=0.17). BTA injections were well tolerated without significant adverse effects.
EUS-guided injection of BTA into gastric muscularis propria can be performed safely with minimal adverse effects. A dose of 300 U BTA significantly enhances satiation, is associated with weight loss, and may slow gastric emptying. Further study of higher dose BTA in obese subjects is warranted.
Obesity; Endoscopic ultrasound; Botulinum toxin; Gastric emptying; Satiation