Comparison of Lactase Variant MCM6 -13910 C>T Testing and Self-report of Dairy Sensitivity in Patients With Irritable Bowel Syndrome.

GOALS: To evaluate agreement of MCM6-13910 with self-report of dairy sensitivity (DS) and lactose hydrogen methane breath test (LHMBT) results in subjects with irritable bowel syndrome (IBS). BACKGROUND: IBS is a functional gastrointestinal disorder with symptoms including abdominal pain, variable bowel habits, and bloating. Adult patients with lactose malabsorption may present with similar symptoms. Patients with lactose malabsorption have a lactase nonpersistent (LNP) phenotype. Recent studies found 2 single nucleotide polymorphisms associated with LNP: G/A-22018 and C/T-13910. STUDY: Genotyping the MCM6-13910 variant of LNP in 538 IBS patients and 317 controls (without IBS). Subjects completed questionnaires pertaining to gastrointestinal problems and dietary consumption, with charts abstracted. RESULTS: Self-reported DS was higher in IBS (45%) than controls (9.8%, odds ratio=6.46, P<0.001). The C/C-13910 genotype was similar in IBS cases and controls, 81 (15.1%) and 47 (14.8%). Among subjects reporting DS, 49 (18.0%) had the C/C genotype. Overall agreement between genotype and self-reported DS was 0.06 in IBS and 0.07 in controls. There were 20 subjects with LHMBT results; 3 had positive results, 17 were negative. LNP genotypes were found in all 3 of positive LHMBT results; 16 had negative LHMBT among the 17 who were lactase persistent. Agreement between C/C-13910 genotype and LHMBT was excellent with κ-statistic of 0.83 (0.50-1.00). CONCLUSIONS: In IBS patients, self-report of lactose intolerance are highly prevalent but are a poor indicator of underlying C/C-13910 genotype. LHMBT had excellent agreement with C/C-13910 genotype.

Polymorphisms of 5-HTT LPR and GNß3 825C>T and Response to Antidepressant Treatment in Functional Dyspepsia: A Study from The Functional Dyspepsia Treatment Trial.

OBJECTIVES: The Functional Dyspepsia Treatment Trial reported that amitriptyline (AMI) was associated with adequate relief of functional dyspepsia (FD) symptoms, but the pharmacogenetics of antidepressant response in FD are not known. GNß3 825C>T CC genotype has been previously linked to FD and TT genotype to antidepressant response in depression. The ss genotype of the 5-HTT LPR variant of the serotonin transporter gene (SLC6A4) has been linked to selective serotonin reuptake inhibitor (SSRI) response. We aimed to examine whether GNß3 825C>T and 5-HTT LPR polymorphisms result in differential treatment effects in FD patients receiving antidepressant therapy. METHODS: Participants were randomized to receive placebo, 50 mg AMI, or 10 mg escitalopram (ESC). The primary end point was adequate relief for ≥5 weeks of the last 10 weeks. Genotyping of GNß3 825C>T and 5-HTT LPR was performed utilizing PCR-based methods. RESULTS: GNß3 825C>T and 5-HTT LPR genotype data were available for 256 (88%) and 246 (84%) patients, respectively. Both polymorphisms were in Hardy-Weinberg equilibrium. In tests for differential treatment, neither 5-HTT LPR nor GNß3 825C>T genotype influenced response to therapy (P=0.89 and P=0.54, respectively). Although there was a tendency for a more favorable response to ESC in the SS/LS genotype compared to the LL genotype groups (40% vs. 31% reporting adequate relief of FD symptoms) among those in the ESC treatment arm, this was not significant (P=0.43). CONCLUSIONS: GNß3 825C>T and 5-HTT LPR genetic variants do not alter treatment response to tricyclic and SSRI antidepressants in FD.

Effect of Amitriptyline and Escitalopram on Functional Dyspepsia: A Multicenter, Randomized Controlled Study.

BACKGROUND & AIMS: Antidepressants are frequently prescribed to treat functional dyspepsia (FD), a common disorder characterized by upper abdominal symptoms, including discomfort or postprandial fullness. However, there is little evidence of the efficacy of these drugs in patients with FD. We performed a randomized, double-blind, placebo-controlled trial to evaluate the effects of antidepressant therapy on symptoms, gastric emptying (GE), and meal-induced satiety in patients with FD. METHODS: We performed a study at 8 North American sites of patients who met the Rome II criteria for FD and did not have depression or use antidepressants. Patients (n = 292; 44 ± 15 years old, 75% were female, 70% with dysmotility-like FD, and 30% with ulcer-like FD) were randomly assigned to groups given placebo, 50 mg amitriptyline, or 10 mg escitalopram for 10 weeks. The primary end point was adequate relief of FD symptoms for ≥5 weeks of the last 10 weeks (of 12). Secondary end points included GE time, maximum tolerated volume in Nutrient Drink Test, and FD-related quality of life. RESULTS: An adequate relief response was reported by 39 subjects given placebo (40%), 51 given amitriptyline (53%), and 37 given escitalopram (38%) (P = .05, after treatment, adjusted for baseline balancing factors including all subjects). Subjects with ulcer-like FD given amitriptyline were >3-fold more likely to report adequate relief than those given placebo (odds ratio = 3.1; 95% confidence interval: 1.1-9.0). Neither amitriptyline nor escitalopram appeared to affect GE or meal-induced satiety after the 10-week period in any group. Subjects with delayed GE were less likely to report adequate relief than subjects with normal GE (odds ratio = 0.4; 95% confidence interval: 0.2-0.8). Both antidepressants improved overall quality of life. CONCLUSIONS: Amitriptyline, but not escitalopram, appears to benefit some patients with FD, particularly those with ulcer-like (painful) FD. Patients with delayed GE do not respond to these drugs. ClinicalTrials.gov ID: NCT00248651.

Outcomes of Ultrasound-Guided Trigger Point Injection for Abdominal Wall Pain.

BACKGROUND: Abdominal wall pain (AWP) is an important cause of chronic abdominal pain. History and physical examination are critical to the diagnosis of AWP. Trigger point injection (TPI) using either a steroid or a local anesthetic or a combination of both is often used to treat AWP. AIM: To determine the efficacy of ultrasound-guided TPI and to determine the predictors of a successful response. METHODS: Patients who received ultrasound-guided TPI between July 2010 and June 2011 were surveyed. The primary outcome was determined using the Treatment Efficacy Questionnaire (TEQ). Electronic medical records were reviewed to determine patient, pain and TPI characteristics. Linear regression was used to determine the predictors of a successful response on the TEQ. RESULTS: Right upper quadrant was the most common site of AWP, and the median pain duration was 12 months. Pain was rated as >8 (1-10 scale) by 57 % and 30 % described it as an ache. Narcotic use was reported in 38 %, and 73 % had a history of at least one abdominal surgery. Forty-four of the 120 (37 %) patients met the criteria for responder on the TEQ. Compared to before treatment, 36 % reported being "significantly better" and 22 % "slightly better." Multiple linear regression analysis showed that higher somatization negatively predicted response. None of the other historical, examination or TPI characteristics were associated with response to the TPI. CONCLUSION: TPI can provide significant, long-term symptom relief in a third of patients with chronic abdominal pain attributed to AWP. Somatization was inversely related to the treatment success.

Evidence Against Routine Testing of Patients With Functional Gastrointestinal Disorders for Celiac Disease: A Population-based Study.

BACKGROUND & AIMS: Celiac disease has been linked to irritable bowel syndrome (IBS)-like symptoms in outpatient clinics. Guidelines recommend that all patients with IBS-like symptoms undergo serologic testing for celiac disease, but there is controversy over whether celiac disease is more prevalent in populations with IBS-like symptoms. We aimed to determine whether positive results from serologic tests for celiac disease are associated with IBS and other functional gastrointestinal disorders (FGIDs) in a large U.S. white population. METHODS: Validated, self-report bowel disease questionnaires (BDQs) were sent to randomly selected cohorts of Olmsted County, Minnesota residents. In separate protocols, serum samples were collected from more than 47,000 Olmsted County residents without a prior diagnosis of celiac disease; we performed serologic tests for celiac disease on stored serum samples from residents who completed the BDQ. Logistic regression was used to test for the association between serologic markers of celiac disease (positive vs negative) and individual FGIDs. RESULTS: A total of 3202 subjects completed the BDQ and had serum available for testing. IBS was identified in 13.6% of these subjects (95% confidence interval [CI], 12.4%-14.8%), and any gastrointestinal symptom occurred in 55.2% (95% CI, 53.5%-56.9%). The prevalence of celiac disease on the basis of serologic markers was 1.0% (95% CI, 0.7%-1.4%). IBS was less prevalent in patients with celiac disease (3%) than patients without celiac disease (14%), although the difference was not statistically significant (odds ratio, 0.2; 95% CI, 0.03-1.5). Abdominal pain, constipation, weight loss, and dyspepsia were the most frequent symptom groups in subjects who were seropositive for celiac disease, but none of the gastrointestinal symptoms or disorders were significantly associated with celiac disease serology. CONCLUSIONS: Symptoms indicative of FGIDs and seropositive celiac disease are relatively common in a U.S. white community. Testing for celiac disease in patients with IBS in the community may not have a significantly increased yield over population-based screening in the United States.

Loss-of-function of the voltage-gated sodium channel NaV1.5 (channelopathies) in patients with irritable bowel syndrome.

BACKGROUND & AIMS: SCN5A encodes the α-subunit of the voltage-gated sodium channel NaV1.5. Many patients with cardiac arrhythmias caused by mutations in SCN5A also have symptoms of irritable bowel syndrome (IBS). We investigated whether patients with IBS have SCN5A variants that affect the function of NaV1.5. METHODS: We performed genotype analysis of SCN5A in 584 persons with IBS and 1380 without IBS (controls). Mutant forms of SCN5A were expressed in human embryonic kidney-293 cells, and functions were assessed by voltage clamp analysis. A genome-wide association study was analyzed for an association signal for the SCN5A gene, and replicated in 1745 patients in 4 independent cohorts of IBS patients and controls. RESULTS: Missense mutations were found in SCN5A in 13 of 584 patients (2.2%, probands). Diarrhea-predominant IBS was the most prevalent form of IBS in the overall study population (25%). However, a greater percentage of individuals with SCN5A mutations had constipation-predominant IBS (31%) than diarrhea-predominant IBS (10%; P < .05). Electrophysiologic analysis showed that 10 of 13 detected mutations disrupted NaV1.5 function (9 loss-of-function and 1 gain-of-function function). The p. A997T-NaV1.5 had the greatest effect in reducing NaV1.5 function. Incubation of cells that expressed this variant with mexiletine restored their sodium current and administration of mexiletine to 1 carrier of this mutation (who had constipation-predominant IBS) normalized their bowel habits. In the genome-wide association study and 4 replicated studies, the SCN5A locus was strongly associated with IBS. CONCLUSIONS: About 2% of patients with IBS carry mutations in SCN5A. Most of these are loss-of-function mutations that disrupt NaV1.5 channel function. These findings provide a new pathogenic mechanism for IBS and possible treatment options.

Lack of familial aggregation in chronic constipation excluding irritable bowel syndrome: a population-based study.

BACKGROUND: Despite strong evidence supporting a genetic and gene-environment interaction in the irritable bowel syndrome (IBS), the role of genes and early life in another common functional bowel disorder, chronic constipation (CC), have been little studied. AIM: To determine whether familial aggregation occurs in CC and whether risk factors differed in those with family members. METHODS: A randomly selected population-based cohort from Olmsted County, MN, was surveyed (n = 8,006); 3,831 completed questionnaires (response rate 48 %). Cases were identified based upon their responses to a validated questionnaire and meeting Rome criteria for CC. Controls were matched one to one by age and gender. IBS (by Rome II criteria) was excluded. Recruitment of case and control probands occurred in 2010-2011 by mailing a family information form; then, first-degree relatives (FDR) were mailed a questionnaire. All potential proband participants were not informed of CC status. RESULTS: Overall 1,185 cases who met criteria for CC without symptoms of IBS and 1,185 controls were surveyed; 309 case and 336 control probands provided data. The proportion of family members having CC was not associated with case status, and the constipation status of FDR was not significantly associated with case-controls status of the respective probands. Symptom burden in FDR was associated with gender and SSC score, but not age or proband status. CONCLUSIONS: No evidence of familial aggregation was observed in adults from the community with CC (excluding IBS). Our data suggest environmental factors in later life more likely account for adult CC.

Effects of Birth Cohorts on the Irritable Bowel Syndrome Support Early-Life Risk Factors.

BACKGROUND: Irritable bowel syndrome (IBS) is common with prevalence reported between 10 and 20 %. IBS clusters in families but it is unknown whether this is explained by a common environment, genes, or both. If early-life factors are important, IBS might be expected to demonstrate a birth cohort phenomenon. AIM: To investigate whether there is a birth cohort phenomenon for subjects with IBS. METHODS: Validated questionnaires were sent to a random sample of Olmsted County, Minnesota, residents who recorded gastrointestinal symptoms; IBS diagnosis was based on the modified Rome criteria. Birth cohorts were chosen a priori based on historical national trends in birth weights using 10-year increments. Logistic regression was used to develop odds ratios to assess the association of IBS with calendar period, birth cohort, age, gender, and somatic symptom score. RESULTS: A total of 4,893 surveys were completed with an overall survey response rate of 58 %. The survey responders were between 25 and 94 years of age and 53 % were female. The overall prevalence of IBS was 16.2 % (95 % CI 15.3-17.4). The univariate association of IBS with birth cohort was significant (p < 0.001) as was the association adjusted for age and gender. The prevalence of IBS was highest for the birth cohort 1963-1972 with an odds ratio of 2.6 (95 % CI 0.97-7.0, p = 0.058). CONCLUSIONS: Population-based data support a possible birth cohort phenomenon in IBS. If correct, early-life risk factors likely play a key role in the development of IBS.

Screening for Barrett's esophagus: results from a population-based survey.

BACKGROUND: Screening for Barrett's esophagus (BE) and adenocarcinoma (EAC) is controversial, but interest remains in finding the optimal method. Attitudes on screening within the community are unknown. We aimed to assess these attitudes via a survey. STUDY: A mixed-mode survey was conducted in adults >50 years to assess awareness regarding BE, willingness to participate in screening, and preferences regarding method of screening. Methods evaluated were sedated endoscopy (sEGD), unsedated transnasal endoscopy (uTNE) and video capsule (VCE). RESULTS: A total of 136 from 413 (33%) adults responded [47% males, mean (SD) age 63 (10.2) years], and 26% of responders knew of BE at baseline. After reading the information on BE, 72% were interested in screening. A history of undergoing screening tests and GI symptoms were predictive of interest. Unsedated techniques were preferred by 64% (VCE: 56% and uTNE: 8%) versus sEGD (36%). CONCLUSIONS: The majority of adults were willing to undergo screening for BE/EAC, with a preference for unsedated techniques.

Factors associated with persistent and nonpersistent chronic constipation, over 20 years.

BACKGROUND & AIMS: The prevalence of chronic constipation (CC) has been reported to be as high as 20% in the general population, but little is known about its natural history. We estimated the natural history of CC and characterized features of persistent CC and nonpersistent CC, compared with individuals without constipation. METHODS: In a prospective cohort study, we analyzed data collected from multiple, validated surveys (minimum of 2) of 2853 randomly selected subjects, over a 20-year period (median, 11.6 years). Based on responses, subjects were characterized as having persistent CC, nonpersistent CC, or no constipation. We assessed the association between constipation status and potential risk factors using logistic regression models, adjusting for age and sex. RESULTS: Of the respondents, 84 had persistent CC (3%), 605 had nonpersistent CC (21%), and 2164 had no symptoms of constipation (76%). High scores from the somatic symptom checklist (odds ratio [OR] = 2.1; 95% confidence interval [CI], 1.3-3.4) and frequent doctor visits (OR = 2.0; 95% CI, 1.0-3.8) were significantly associated with persistent CC, compared with subjects with no constipation symptoms. The only factor that differed was increased use of laxatives or fiber among subjects with persistent CC (OR = 3.0; 95% CI, 1.9-4.9). CONCLUSIONS: The prevalence of constipation might be exaggerated-the proportion of the population with persistent CC is low (3%). Patients with persistent and nonpersistent CC have similar clinical characteristics, although individuals with persistent CC use more laxatives or fiber. CC therefore appears and disappears among certain patients, but we do not have enough information to identify these individuals in advance.

Challenges and lessons learned in conducting comparative-effectiveness trials.

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.

Risk of gastroparesis in subjects with type 1 and 2 diabetes in the general population.

OBJECTIVES: In patients with diabetes mellitus (DM) and upper gastrointestinal symptoms, a diagnosis of diabetic gastroparesis is often considered, but population-based data on the epidemiology of diabetic gastroparesis are lacking. We aimed to estimate the frequency of and risk factors for gastroparesis among community subjects with DM. METHODS: In this population-based, historical cohort study, the medical records linkage system of the Rochester Epidemiology Project was used to identify 227 Olmsted County, MN residents with type 1 DM in 1995, a random sample of 360 residents with type 2 DM, and an age- and sex-stratified random sample of 639 nondiabetic residents. Using defined diagnostic criteria, we estimated the subsequent risk of developing gastroparesis in each group through 2006. The risk in DM, compared with frequency-matched community controls, was assessed by Cox proportional hazards modeling. RESULTS: The cumulative proportions developing gastroparesis over a 10-year time period were 5.2% in type 1 DM, 1.0% in type 2 DM, and 0.2% in controls. The age- and gender-adjusted hazard ratios (HRs) for gastroparesis (relative to controls) was 33 (95% confidence interval (CI): 4.0, 274) in type 1 DM and 7.5 (95% CI: 0.8, 68) in type 2 DM. The risk of gastroparesis in type 1 DM was significantly greater than in type 2 DM (HR: 4.4 (1.1, 17)). Heartburn (HR: 6.6 (1.7, 25)) at baseline was associated with diabetic gastroparesis in type 1 DM. CONCLUSIONS: Gastroparesis is relatively uncommon in patients with DM, although an increased risk for gastroparesis was observed in type 1 DM.

Epidemiology and natural history of intestinal metaplasia of the gastroesophageal junction and Barrett's esophagus: a population-based study.

OBJECTIVES: Population-based data on the epidemiology and outcomes of subjects with intestinal metaplasia of the gastroesophageal junction (IMGEJ) and Barrett's esophagus (BE) are limited. The objectives of this study were to (i) estimate the incidence of IMGEJ and BE diagnosed from clinically indicated endoscopy in Olmsted County, MN, over three decades (1976-2006) and prevalence as of 1 January 2007, (ii) compare baseline characteristics of subjects with IMGEJ and BE, and (iii) study the natural history and survival of both cohorts. METHODS: This was a population-based cohort study. The study setting was Olmsted County, MN. Patients with BE (columnar segment >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. RESULTS: In all, 487 patients (401 with BE and 86 with IMGEJ) were identified and followed for a median interval of 7 (BE subjects) to 8 (IMGEJ subjects) years. Subjects with BE were older, heavier, reported reflux symptoms more often, and had higher prevalence of advanced neoplasia than those with IMGEJ. No patient with IMGEJ progressed to esophageal adenocarcinoma (EAC) in contrast to BE subjects who had a cumulative risk of progression of 7% at 10 years and increased risk of death from EAC (standardized mortality ratio 9.62). The overall survival of subjects with BE and IMGEJ did not differ from that expected in similar age- and sex-distributed white Minnesota populations. CONCLUSIONS: Subjects with IMGEJ appear to have distinct clinical characteristics and substantially lower cancer progression risk compared to those with BE.

Direct medical costs of constipation from childhood to early adulthood: a population-based birth cohort study.

BACKGROUND: Although direct medical costs for constipation-related medical visits are thought to be high, to date there have been no studies examining whether longitudinal resource use is persistently elevated in children with constipation. Our aim was to estimate the incremental direct medical costs and types of health care use associated with constipation from childhood to early adulthood. METHODS: A nested case-control study was conducted to evaluate the incremental costs associated with constipation. The original sample consisted of 5718 children in a population-based birth cohort who were born during 1976 to 1982 in Rochester, MN. The cases included individuals who presented to medical facilities with constipation. The controls were matched and randomly selected among all noncases in the sample. Direct medical costs for cases and controls were collected from the time subjects were between 5 and 18 years of age or until the subject emigrated from the community. RESULTS: We identified 250 cases with a diagnosis of constipation in the birth cohort. Although the mean inpatient costs for cases were $9994 (95% Confidence interval [CI] 2538-37,201) compared with $2391 (95% CI 923-7452) for controls (P = 0.22) during the time period, the mean outpatient costs for cases were $13,927 (95% CI 11,325-16,525) compared with $3448 (95% CI 3771-4621) for controls (P < 0.001) during the same time period. The mean annual number of emergency department visits for cases was 0.66 (95% CI 0.62-0.70) compared with 0.34 (95% CI 0.32-0.35) for controls (P < 0.0001). CONCLUSIONS: Individuals with constipation have higher medical care use. Outpatient costs and emergency department use were significantly greater for individuals with constipation from childhood to early adulthood.

Neural autoantibody evaluation in functional gastrointestinal disorders: a population-based case-control study.

BACKGROUND: Our goal is to investigate the serum profile of neural autoantibodies in community-based patients with irritable bowel syndrome (IBS) or functional dyspepsia. The pathogenesis of functional gastrointestinal (GI) disorders, including IBS and dyspepsia, are unknown. Theories range from purely psychological to autoimmune alterations in GI tract neuromuscular function. METHODS: The study subjects, based in Olmsted County, MN, reported symptoms of functional dyspepsia or IBS (n = 69), or were asymptomatic controls (n = 64). Their coded sera were screened for antibodies targeting neuronal, glial, and muscle autoantigens. RESULTS: The prevalence of neural autoantibodies with functional GI disorders did not differ significantly from controls (17% vs. 13%; P = 0.43). In no case was a neuronal or glial nuclear autoantibody or enteric neuronal autoantibody identified. Neuronal cation channel antibodies were identified in 9% of cases (voltage-gated potassium channel [VGKC] in one dyspepsia case and one IBS case, ganglionic acetylcholine receptor [AChR] in four IBS cases) and in 6% of controls (ganglionic AChR in one, voltage-gated calcium channel [VGCC], N-type, in two and VGKC in one; P = 0.36). The frequency of glutamic acid decarboxylase-65 (GAD65) autoantibodies was similar in cases (10%) and controls (5%; P = 0.23). CONCLUSIONS: Our data do not support neural autoimmunity as the basis for most IBS or functional dyspepsia cases.

The incidence, prevalence, and outcomes of patients with gastroparesis in Olmsted County, Minnesota, from 1996 to 2006.

BACKGROUND & AIMS: The epidemiology of gastroparesis is unknown. We aimed to determine the incidence, prevalence, and outcome of gastroparesis in the community. METHODS: Using the Rochester Epidemiology Project, a medical records linkage system in Olmsted County, Minnesota, we identified county residents with potential gastroparesis. The complete medical records were reviewed by a gastroenterologist. Three diagnostic definitions were used: (1) definite gastroparesis, delayed gastric emptying by standard scintigraphy and typical symptoms for more than 3 months; (2) probable gastroparesis, typical symptoms and food retention on endoscopy or upper gastrointestinal study; (3) possible gastroparesis, typical symptoms alone or delayed gastric emptying by scintigraphy without gastrointestinal symptoms. Poisson regression was used to assess the association of incidence rates with age, sex, and calendar period. RESULTS: Among 3604 potential cases of gastroparesis, 83 met diagnostic criteria for definite gastroparesis, 127 definite plus probable gastroparesis, and 222 any of the 3 definitions of gastroparesis. The age-adjusted (to the 2000 US white population) incidence per 100,000 person-years of definite gastroparesis for the years 1996-2006 was 2.4 (95% confidence interval [CI], 1.2-3.8) for men and 9.8 (95% CI, 7.5-12.1) for women. The age-adjusted prevalence of definite gastroparesis per 100,000 persons on January 1, 2007, was 9.6 (95% CI, 1.8-17.4) for men and 37.8 (95% CI, 23.3-52.4) for women. Overall survival was significantly lower than the age- and sex-specific expected survival computed from the Minnesota white population (P<.05). CONCLUSIONS: Gastroparesis is an uncommon condition in the community but is associated with a poor outcome.

A shift in the clinical spectrum of eosinophilic gastroenteritis toward the mucosal disease type.

BACKGROUND & AIMS: Eosinophilic gastroenteritis (EG) is a rare disorder characterized by eosinophilic infiltration of the gastrointestinal (GI) tract. Despite the increasing prevalence of eosinophilic GI disorders, the epidemiology of EG has not been well studied. We evaluated the clinical spectrum of EG. METHODS: We reviewed data from patients diagnosed with EG, allergic gastroenteropathy, or eosinophilia and referred to gastroenterologists from 1987 to 2007 (n = 59; 52 with mucosal, 3 with muscularis, and 4 with subserosal disease). The study included subjects diagnosed with EG and those with a history that suggested EG, defined by GI symptoms; eosinophilic infiltration of the GI tract, eosinophilic ascites, or characteristic radiographic findings with eosinophilia; and no parasitic or extraintestinal disease. Findings were compared with those from patients with unexplained GI symptoms and peripheral eosinophilia (n = 11). RESULTS: Associations between clinical variables and EG subgroups did not differ between patients with EG and peripheral eosinophilia. Fifty percent of patients with EG who underwent food allergy testing had a positive test result; only 32% of those with EG who underwent radiographic imaging had positive test results. Patients with EG received steroid therapy; 75% with mucosal, 67% with muscle, and 100% with subserosal disease received prednisone. Eighty-eight percent of patients who received only steroids (mean follow-up period, 7 mo) and 94% of patients who received steroids in combination with another therapy (mean follow-up period, 4 mo) had improved or resolved disease. CONCLUSIONS: Unlike eosinophilic esophagitis, EG is rare. Results from this large study suggest that EG disease type has shifted toward that of the mucosal layer.

Impact of functional gastrointestinal disorders on survival in the community.

OBJECTIVES: Functional gastrointestinal disorders (FGIDs) comprise a constellation of symptoms that have no identifiable structural or biochemical abnormality. In view of the lack of data from large-scale population-based studies evaluating the effects of these disorders on survival, we aimed to examine whether FGIDs are associated with impaired survival. METHODS: Between 1988 and 1993, valid self-report questionnaires that recorded gastrointestinal symptoms required for the diagnosis of irritable bowel syndrome (IBS), chronic constipation, chronic diarrhea, dyspepsia, and abdominal pain were mailed to randomly selected cohorts of Olmsted County, Minnesota residents. Minnesota administrative death records were used to identify which of the survey respondents had died over the follow-up period (through April 2008). The association between survival and each FGID was assessed using proportional hazards regression models with univariate and adjusted hazard ratios (HRs, 95% confidence intervals (CIs)), adjusting for age at time of survey, gender, smoking, alcohol, marital status, and Charlson Comorbidity Index (CCI). RESULTS: Of the 5,262 randomly selected eligible subjects who received a questionnaire, a total of 4,176 responded to the surveys (overall response rate 79%). From these respondents, 243 subjects were excluded because of lack of research authorization (or were registered solely at a different medical institution in Olmsted County, MN), resulting in 3,933 eligible subjects for analysis (eligible response rate 75%); 10% reported symptoms of IBS; 16% chronic constipation; 18% chronic diarrhea; 2% dyspepsia; and 15% abdominal pain. At baseline, the mean (s.d.) age was 54 (18) years, and 52% were female. No association with overall survival was detected for IBS (HR=1.06 (95% CI: 0.86-1.32)), chronic diarrhea (HR=1.03 (95% CI: 0.90-1.19)), abdominal pain (HR=1.09 (95% CI: 0.92-1.30)), or dyspepsia (HR=1.08 (95% CI: 0.58-2.02)). Reporting symptoms of chronic constipation was associated with poorer survival (HR=1.23 (95% CI: 1.07-1.42)). This association remained significant after adjusting for the CCI (HR=1.19 (95% CI: 1.03-1.37)). CONCLUSIONS: In this large population-based cohort study with over 30,000 person-years of follow-up, no significant association was observed between survival and IBS, chronic diarrhea, dyspepsia, or abdominal pain. Furthermore, no association was found between increasing burden of FGIDs and survival. However, in contrast to these other FGIDs, subjects with symptoms of chronic constipation were found to be at increased risk of poorer survival. Further investigation is required to determine the cause of this observed association.

Diarrhea-predominant irritable bowel syndrome is associated with diverticular disease: a population-based study.

OBJECTIVES: A subset of patients with colonic diverticular disease have chronic gastrointestinal symptoms, and some have a clinical diagnosis of irritable bowel syndrome (IBS), but whether IBS and diverticular disease are linked is uncertain. We aimed to evaluate this association in the community. METHODS: A population-based, cross-sectional survey was conducted by mailing a valid symptom questionnaire to the eligible residents of Olmsted County, MN, aged 30-95 years. Colonic diverticular disease (diverticulosis and diverticulitis) was ascertained through a review of the complete medical history of all responders. Subjects with at least one relevant test (colonoscopy, computed tomography (CT) scan, CT colonography, or barium enema) were included. IBS was defined using Rome II criteria. RESULTS: Among 2,267 eligible respondents, there were 1,712 subjects who had undergone colon testing (76%): 919 women (54%); mean (+/-s.d.) age 65 (+/-11 years). Colonic diverticular disease was identified in 44.4% (95% confidence interval (CI) 42.1-46.8) of the subject. IBS was reported by 8.8% (95% CI 6.9-11.0) of men and 17.0% (95% CI 14.6-19.6) of women. After adjusting for age and gender, the presence of IBS was associated with an increased odds for diverticulosis (odds ratio (OR) =1.8, 95% CI 1.3-2.4) but not diverticulitis (OR=1.7, 95% CI 0.9-3.2). In those 65 years of age or older, the presence of IBS was associated with a ninefold higher odds for diverticulosis (OR=9.4, 95% CI 5.8-15.1). Relative to the non-IBS subgroup, diarrhea-predominant IBS and mixed IBS were significantly associated with an increased odds for diverticular disease (OR=1.9, 95% CI 1.1-3.2; OR=2.6, 95% CI 1.0-6.4, respectively). CONCLUSIONS: There is a significantly increased odds for colonic diverticulosis in subjects with IBS (relative to those without IBS). These results suggest that IBS and colonic diverticular disease may be connected.

A randomized, double-blind, placebo-controlled trial of St John's wort for treating irritable bowel syndrome.

OBJECTIVES: St John's wort (SJW) is known to effectively treat patients with mild-to-moderate depression. Antidepressants are frequently used to treat irritable bowel syndrome (IBS). To date, no study that examines the efficacy of SJW in IBS has been carried out. The aim of this study was to evaluate the efficacy of SJW in IBS after 12 weeks. METHODS: In this randomized, double-blind, placebo-controlled trial, 70 participants with an established diagnosis of IBS were randomized and assigned by concealed allocation to either SJW or placebo. Both treatment arms were balanced on symptom subtype. The primary end point was self-reported overall bowel symptom score (BSS) at 12 weeks. Secondary end points were individual BSS for diarrhea (D-BSS), constipation (C-BSS), pain or discomfort, and bloating; adequate relief (AR) of IBS on at least 50% of the last 4 weeks of therapy; and IBS quality-of-life score at 12 weeks. RESULTS: In all, 86% of the participants were women, and the median age was 42 years. Overall, 29% had C-IBS, 37% D-IBS, and 31% had mixed IBS. Both groups reported decreases in overall BSS from baseline, with the placebo arm having significantly lower scores at 12 weeks (P=0.03) compared with SJW. These patterns of improvement were mirrored in the secondary end points with the placebo group faring better than the SJW-treated group, with significant differences observed at week 12 for D-BSS (P=0.03) and percent with AR (P=0.02). A similar proportion of subjects in each treatment group (SJW: 51% vs. placebo: 54%) believed that the study drug they received decreased IBS life interferences (P=0.79). CONCLUSIONS: SJW was a less effective treatment for IBS than placebo.