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1.  So you aspire to be a Professor? 
PMCID: PMC2785069  PMID: 20037627
2.  Acid and non-acid reflux in patients refractory to proton pump inhibitor therapy: Is gastroparesis a factor? 
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.
PMCID: PMC3787349  PMID: 24115816
Gastroparesis; Non-acid gastroesophageal reflux; Acid gastroesophageal reflux; Multi-channel intraluminal impedance; Functional bowel disorder
3.  The effects of aging on the onset and persistence of unexplained abdominal pain: a population-based study 
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.
PMCID: PMC4070656  PMID: 24304163
4.  Associations between Medication Use and Functional Gastrointestinal Disorders: A Population-Based Study 
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.
PMCID: PMC3631281  PMID: 23360217
Functional GI disorders; proton pump inhibitors; antidepressants; narcotics
5.  Irritable bowel syndrome and chronic pelvic pain: A population-based study 
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.
PMCID: PMC3935283  PMID: 20375730
IBS; pelvic pain; sexual dysfunction
6.  Dissecting GI Phenotype – Genotype Relationships in GERD and Dyspepsia: An SNP Here and an SNP There! 
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.
PMCID: PMC3935284  PMID: 19174788
7.  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.
PMCID: PMC3935288  PMID: 22552235
8.  Novel mechanisms in functional dyspepsia 
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.
PMCID: PMC4066114  PMID: 16521177
Functional dyspepsia; Gastric function; Pathophysiology
9.  Psychosocial Distress and Somatic Symptoms in Community Subjects With Irritable Bowel Syndrome: A Psychological Component Is the Rule 
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.
PMCID: PMC3772628  PMID: 19491833
10.  Novel associations with dyspepsia: A community based study of familial aggregation, sleep dysfunction and 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.
PMCID: PMC3748718  PMID: 19496951
11.  Screening for Barrett’s Esophagus: Results from a Population-Based Survey 
Digestive diseases and sciences  2014;59(8):1831-1850.
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.
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).
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 %).
The majority of adults were willing to undergo screening for BE/EAC, with a preference for unsedated techniques.
PMCID: PMC4387565  PMID: 24652109
Barrett’s esophagus; Screening; Esophageal adenocarcinoma; Transnasal endoscopy; Capsule endoscopy; Survey
12.  Loss-of-function of the Voltage-gated Sodium Channel NaV1.5 (Channelopathies) in Patients with Irritable Bowel Syndrome 
Gastroenterology  2014;146(7):1659-1668.
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.
We performed genotype analysis of SCN5A in 584 persons with IBS and 1380 without (controls). Mutant forms of SCN5A were expressed in HEK-293 cells, and functions were assessed by voltage clamp analysis. A genome-wide association study (GWAS) was analyzed for an association signal for the SCN5A gene, and replicated in 1745 patients in 4 independent cohorts of IBS patients and controls.
Missense mutations were found in SCN5A in 13/584 patients (2.2%, probands). Diarrhea-predominant IBS (IBS-D) 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 (IBS-C, 31%) than IBS-D (10%, P<.05). Electrophysiologic analysis showed that 10/13 detected mutations disrupted NaV1.5 function (9 reduced and 1 increased function); 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; administration of mexiletine to 1 carrier of this mutation (who had IBS-C) normalized their bowel habits. In the GWAS and 4 replicated studies, the SCN5A locus was strongly associated with IBS.
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.
PMCID: PMC4096335  PMID: 24613995
genetics; GI motility; voltage-gated sodium channel; polymorphism
13.  Variation in Prevalence, Diagnostic Criteria, and Initial Management Options for Eosinophilic Gastrointestinal Diseases in the United States 
Variation in the prevalence of eosinophilic gastrointestinal diseases in different geographical regions has not been extensively studied. The aim of the present study was to define the regional and national prevalence of eosinophilic gastrointestinal diseases, and differences in practice approaches.
Patients and Methods
We administered a survey electronically to members of the American College of Gastroenterology, the American Academy of Allergy, Asthma, and Immunology, and the North American Society Pediatric Gastroenterology, Hepatology, and Nutrition. Questions pertained to the number and proportion of patients seen with eosinophilic gastroenteritis or colitis and eosinophilic esophagitis (EoE), and methods used to diagnose and treat these conditions.
A total of 1836 physicians responded from 10,874 requests (17% response). Extrapolating responses from our US sample, we estimated an overall prevalence of 52 and 28/100,000 for EoE and eosinophilic gastroenteritis or colitis. The patient burden of EoE is higher in urban (0.58) and suburban (0.44) compared with rural settings (0.36, P <0.0065), observations consistent with other allergic disorders. There was also increased prevalence in northeast region when calculated by prevalence per 100,000. There was considerable variability in criteria and initial treatment options used to diagnose EoE. Only one-third of respondents reported using diagnostic criteria proposed in a 2007 consensus document. Seventy-one and 35% of respondents reported treating some patients with EoE with a food elimination or elemental diet, respectively.
EoE is diagnosed more often in northeastern states and urban areas. There is considerable variability in diagnostic criteria and initial treatment approach supporting the need for additional clinical trials and consensus development.
PMCID: PMC4450826  PMID: 21057327
eosinophilic esophagitis; eosinophilic gastrointestinal disease; prevalence; treatment options
14.  Epidemiology and Natural History of Intestinal Metaplasia of the Gastroesophageal Junction and Barrett's Esophagus: A Population-Based Study 
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.
PMCID: PMC3150349  PMID: 21483461
15.  Biliary events and an increased risk of new onset irritable bowel syndrome: A population-based cohort study 
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.
PMCID: PMC3335764  PMID: 19086237
16.  HIPAA Authorization and Survey Nonresponse Bias 
Medical care  2011;49(4):365-370.
To extend earlier work1 that demonstrated that a HIPAA authorization form (HAF) introduced potential nonresponse bias (toward healthier respondents).
Research Design
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.
PMCID: PMC3179247  PMID: 21368682
survey methods; HIPAA; response rate; nonresponse bias
17.  Direct medical costs of constipation in children over 15 years: a population-based birth cohort 
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.
PMCID: PMC3212031  PMID: 20890220
Childhood constipation; Direct medical costs; Case-control study
18.  Helicobacter pylori serology in a birth cohort of New Zealanders from age 11 to 26 
AIM: To determine seroprevalence of Helicobacter pylori (H pylori) in the Dunedin Multidisciplinary Health and Development Study (DMHDS) at age 26 in order to investigate seroconversion and seroreversion from age 11 to 26 and the association of seropositivity with risk factors for H pylori infection.
METHODS: Participants in the DMHDS at age 26 and retro-spectively at age 21 were tested for H pylori antibodies using two commercially available ELISA kits. Gender, soci-oeconomic status (SES), smoking, educational attainment and employment at age 26 were tested for association with H pylori seropositivity.
RESULTS: At ages 21 and 26, seroprevalence of H pylori using one or other kit was 4.2% (n = 795) and 6.3% (n = 871) respectively. Seroreversion rate was lower than serocon-version rate (0.11% vs 0.53% per person-year) in contrast to the period from age 11 to 21 when seroreversion rate exceeded seroconversion rate (0.35% vs 0.11% per person-year). Serology in those tested at ages 11, 21, and 26 remained unchanged in 93.6% of the sample. Seroprevalence at age 26 was lower among those with a secondary school qualification (P = 0.042) but was not associated with gender, SES, smoking or employment status.
CONCLUSION: H pylori seroprevalence in a New Zealand birth cohort remains low between ages 11 and 26. H pylori infection remains stable from childhood to adulthood although seroreversion seems to be more common in the adolescent years than in young adults.
PMCID: PMC4316062  PMID: 15929181
H pylori; Seroprevalence; Cohort
19.  Health care seeking for abdominal bloating and visible distention 
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.
PMCID: PMC3217295  PMID: 19563502
Large intestine Organ-based; Abdominal pain Topics; Epidemiology Topics; Motility Topics
20.  Opioid Bowel Dysfunction and Narcotic Bowel Syndrome: A Population-Based Study 
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.
PMCID: PMC3209714  PMID: 19367263
21.  Onset and Risk Factors for Fecal Incontinence in a US Community 
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.
PMCID: PMC3189687  PMID: 19844202
22.  Factor analysis identifies subgroups of constipation 
AIM: To determine whether distinct symptom groupings exist in a constipated population and whether such grouping might correlate with quantifiable pathophysiological measures of colonic dysfunction.
METHODS: One hundred and ninety-one patients presenting to a Gastroenterology clinic with constipation and 32 constipated patients responding to a newspaper advertisement completed a 53-item, wide-ranging self-report questionnaire. One hundred of these patients had colonic transit measured scintigraphically. Factor analysis determined whether constipation-related symptoms grouped into distinct aspects of symptomatology. Cluster analysis was used to determine whether individual patients naturally group into distinct subtypes.
RESULTS: Cluster analysis yielded a 4 cluster solution with the presence or absence of pain and laxative unresponsiveness providing the main descriptors. Amongst all clusters there was a considerable proportion of patients with demonstrable delayed colon transit, irritable bowel syndrome positive criteria and regular stool frequency. The majority of patients with these characteristics also reported regular laxative use.
CONCLUSION: Factor analysis identified four constipation subgroups, based on severity and laxative unresponsiveness, in a constipated population. However, clear stratification into clinically identifiable groups remains imprecise.
PMCID: PMC3070021  PMID: 21472106
Factor analysis; Constipation; Symptoms; Clusters; Laxatives
23.  Epidemiology of Eosinophilic Esophagitis over 3 Decades in Olmsted County, Minnesota 
Background & Aims
Data on secular trends and outcomes of eosinophilic esophagitis (EE) are scarce. We performed a population-based study to assess the epidemiology and outcomes of EE in Olmsted County, Minnesota, over the last 3 decades.
All cases of EE diagnosed between 1976 and 2005 were identified using the Rochester Epidemiology Project resources. Esophageal biopsies with any evidence of esophagitis and/or eosinophilic infiltration were reviewed by a single pathologist. Clinical course (treatment, response and recurrence) was defined using information collected from medical records and prospectively via a telephone questionnaire. Incidence rates per 100,000 person years were directly adjusted for age and sex to the US 2000 population structure.
A total of 78 patients with EE were identified. The incidence of EE increased significantly over the last 3 of the 5-year intervals (from 0.35 [0,0.87]/100000 person-years during 1991–1995 to 9.45 [7.13, 11.77]/100000 person-years during 2001–2005). The prevalence of EE was 55.0 (42.7, 67.2)/100000 persons as of January 1, 2006 in Olmsted County, Minnesota. EE was diagnosed more frequently in late summer/fall. The clinical course of patients with EE was characterized by recurrent symptoms (observed in 41% of patients).
The prevalence and incidence of EE is higher than previously reported. The incidence of clinically diagnosed EE increased significantly over the last 3 decades, in parallel with endoscopy volume and seasonal incidence, and was greatest in late summer/fall. EE also appears to be a recurrent relapsing disease in a substantial proportion of patients.
PMCID: PMC3026355  PMID: 19577011
24.  Functional Dyspepsia Treatment Trial (FDTT): A double-blind, randomized, placebo-controlled trial of antidepressants in functional dyspepsia, evaluating symptoms, psychopathology, pathophysiology and pharmacogenetics 
Contemporary clinical trials  2012;33(3):523-533.
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 ( number NCT00248651).
PMCID: PMC4289143  PMID: 22343090
Amitriptyline; Antidepressive agents; Citalopram; Dyspepsia; Clinical trial; National Institute of Diabetes and Digestive and Kidney Diseases
25.  AJG Series: Molecular Biology for Clinicians Pharmacogenetics and Genomics for Clinicians 
Pharmacogenetics is an evolving field that provides the link between an individual's genetic code and drug metabolism and drug response. This field offers the great promise of individualized medication selection and optimized dosage to maximize treatment response and to minimize adverse side effects. As our understanding of the role of the effects of genetic variants on drug metabolism and body drug processing grows, so does our ability to educate and inform our patients about expected treatment response to the medications being prescribed to them. This brief review will provide an overview of genetics, pharmacogenetics, and current and future examples of genetic variants predicting drug response in gastrointestinal disease, and the limitations and the promise of this exciting and developing field.
PMCID: PMC2901906  PMID: 19550416

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