A pharmacological challenge predicts reversible rectal sensorimotor dysfunctions in women with fecal incontinence.

BACKGROUND: In order to understand the pathophysiology of rectal sensorimotor dysfunctions in women with fecal incontinence (FI) and rectal urgency, we evaluated the effects of a muscarinic antagonist and an adrenergic α2 agonist on these parameters. METHODS: Firstly, rectal distensibility and sensation were evaluated with a barostat and sinusoidal oscillation at baseline and after randomization to intravenous saline or atropine in 16 healthy controls and 44 FI patients. Thereafter, FI patients were randomized to placebo or clonidine for 4 wk; rectal compliance and sensation were revaluated thereafter. The effect of atropine and clonidine on rectal functions and the relationship between them were evaluated. RESULTS: At baseline, compared to controls, rectal capacity was lower (P = .03) while the mean pressure (P = .02) and elastance (P = .01) during sinusoidal oscillation were greater, signifying reduced distensibility, in FI. Compared to placebo, atropine increased (P ≤ .02) the heart rate in controls and FI and reduced (P = .03) the variability in rectal pressures during sinusoidal oscillation in controls. Clonidine increased rectal compliance (P = .04) and reduced rectal capacity (P = .03) in FI. The effects of atropine and clonidine on compliance (r = .44, P = .003), capacity (r = .34, P = .02), pressures during sinusoidal oscillation (r = .3, P = .057), pressure (r = .6, P < .0001), and volume sensory thresholds (r = .48, P = .003) were correlated. CONCLUSIONS: The effects of atropine and clonidine on rectal distensibility and sensation were significantly correlated. A preserved response to atropine suggests that reduced rectal distensibility is partly reversible, mediated by cholinergic mechanisms, and may predict the response to clonidine, providing a pharmacological challenge.

Reproducibility of gastric emptying assessed with scintigraphy in patients with upper GI symptoms.

BACKGROUND: The reproducibility of gastric emptying (GE) measured with scintigraphy in patients is poorly understood. Our aims were to assess the intra and inter-individual reproducibility of these parameters in patients with upper gastrointestinal symptoms. METHODS: Sixty patients (21 diabetics, 39 non-diabetics) with upper gastrointestinal symptoms underwent scintigraphic-assessment of GE of a solid meal (296 kcal, 30% fat) over 4 hours on two occasions at an average interval of 15 days. The concordance correlation coefficient (CCC), intra and inter-individual coefficients of variation (COV) of GE endpoints were analyzed. RESULTS: The GE t1/2 was 134 ± 8 minutes (mean ± SEM) for the first and 128 ± 6 minutes for the second study. The mean (95% CI) CCC between the two studies was 0.79 (0.67, 0.87) for GE at 1 hour, 0.83 (0.75, 0.9) for GE at 2 hours, 0.54 (0.34, 0.7) for GE at 4 hours, and 0.79 (0.68, 0.86) for GE t1/2 . However, in 18 of 60 patients (30%), the characterization of GE as normal, delayed, or rapid differed between the first and second studies. For gastric empting t1/2 , the inter-individual coefficients of variation was 40%; the intra-individual COV was 20%, comparable in diabetics and non-diabetics, and greater in patients with rapid (28%) than delayed (18%) or normal GE (12%). CONCLUSIONS & INFERENCES: Among patients with upper gastrointestinal symptoms, GE measured with scintigraphy is relatively reproducible. In 30% of cases, the interpretation was different between the two assessments. Hence, a diagnosis of gastroparesis based on a single study may occasionally be inaccurate.

Normal values for assessment of anal sphincter morphology, anorectal motion, and pelvic organ prolapse with MRI in healthy women.

BACKGROUND: Endoanal MRI and MR defecography are used to identify anal sphincter injury and disordered defecation. However, few studies have evaluated findings in asymptomatic healthy people. The effects of BMI and parity on rectoanal motion and evacuation are unknown. METHODS: In 113 asymptomatic females (age 50 ± 17 years, Mean ± SD) without risk factors for anorectal trauma, anal sphincter appearance, anorectal motion, and pelvic organ prolapse were evaluated with MRI. The relationship between age, BMI, and parity and structural findings were evaluated with parametric and non-parametric tests. RESULTS: The anal sphincters and puborectalis appeared normal in over 90% of women. During dynamic MRI, the anorectal angle was 100 ± 1º (Mean ± SEM) at rest, 70 ± 2° at squeeze, and 120 ± 2° during defecation. The change in anorectal angle during squeeze (r = -.25, P < .005), but not during evacuation (r = .13, P = .25) was associated with age. In the multivariable models, BMI (P < .01) and parity (P < .01) were, respectively, independently associated with the intersubject variation in the anorectal angle at rest and the angle change during squeeze. Ten percent or fewer women had had descent of the bladder base or uterus 4 cm or more below the pubococcygeal line or a rectocele measuring 4 cm or larger. Only 5% had a patulous anal canal. CONCLUSIONS: In addition to age, BMI and parity also affect anorectal motion in asymptomatic women. These findings provide age-adjusted normal values for rectoanal anatomy and pelvic floor motion.

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

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

Multiple functional gastrointestinal disorders linked to gastroesophageal reflux and somatization: A population-based study.

BACKGROUND: It is unknown why functional gastrointestinal disorders (FGIDs) overlap and limited information exists on risk factors for those with overlap. Our aim was to estimate the prevalence of combinations of FGIDs including reflux (FGIDs-gastroesophageal reflux [GER]), and evaluate potential risk factors for people with multiple disorders in a representative US community. METHODS: A population-based study was conducted by mailing a valid GI symptom questionnaire to an age- and gender-stratified random sample of residents of Olmsted County, MN. Rome III definitions were used to identify people with FGIDs, and GER was defined by weekly or more frequent heartburn or acid regurgitation. The prevalence of people meeting multiple symptom complexes was estimated. Moreover, potential risk factors for people with multiple disorders were evaluated. KEY RESULTS: A total of 3548 people provided data for each of the necessary symptom questions (mean age: 61±16 years, 54% female). Among these 3548 subjects, 2009 (57%) had no FGIDs-GER, 906 (26%) had a pure FGID-GER, 372 (10%) had 2 FGIDs-GER, and 261 (7%) had 3 or more FGIDs-GER. Somatization as assessed by a higher Somatic Symptom Checklist score (OR=3.3, 95% CI [2.7,4.1]) was associated with an increased odds for those with 3 or more FGIDs-GER compared to subjects with a pure FGID-GER adjusting for age and gender. CONCLUSIONS AND INFERENCES: Symptom complex overlap is common rather than rare in the community. GER is an integral symptom complex associated with both upper and lower FGIDs. Somatization is a strong risk factor for multiple FGIDs.

A single-center, prospective, double-blind, sham-controlled, randomized study of the effect of a vibrating capsule on colonic transit in patients with chronic constipation.

BACKGROUND: In an open-label study of 26 patients with IBS-C and chronic constipation, treatment with a vibrating (VIBRANT) capsule twice a week for 7.5 weeks resulted in 88.5% responders. Effects on colonic transit are unclear. We aimed to compare effects of VIBRANT and sham capsule treatment on colonic transit in patients with functional constipation. METHODS: Patients with functional constipation (Rome III criteria) were randomized to VIBRANT or sham capsule treatment for 8 weeks and underwent scintigraphic colonic transit measurements during week 8. We estimated the overall rate of colonic transit from the slope of progression of colonic geometric center over 48 hours. The capsule was activated 8 hours after ingestion, and the vibration sequence included 240 cycles. KEY RESULTS: There were no significant group differences in overall colonic transit [GC48, 2.76 (IQR 2.42-4.03) for sham group and 3.46 (2.55-4.61) for active treatment group (P=.13)]. Additionally, the progression of the isotope through the colon was numerically faster, though not significantly different (slope, P=.14) in the VIBRANT capsule group compared to the sham group. Three participants in the VIBRANT capsule group had accelerated colonic transit at 32 hours and faster colonic transit slope compared to the 95th percentile of the sham group. CONCLUSIONS AND INFERENCES: Although there were no group differences between VIBRANT and sham capsule treatment on colonic transit, at least one (and possibly three) of 12 patients receiving the VIBRANT capsule had faster colonic transit. The vibration parameters to accelerate colonic transit in patients with functional constipation require further optimization.

Reproducibility of high-definition (3D) manometry and its agreement with high-resolution (2D) manometry in women with fecal incontinence.

BACKGROUND: While widely used in clinical practice, the reproducibility of high-definition anorectal manometry (HD-ARM) remains unclear. We evaluated the intra-individual reproducibility of HD-ARM and compared pressures measured with HD-ARM and high-resolution anorectal manometry (HR-ARM). METHODS: Thirty-six women with fecal incontinence had an initial HD-ARM (HD-ARM1); on the same day, after randomization, 21 had a second (HD-ARM2). Sixteen women had a third (HD-ARM3) 4 weeks later. Twenty-five had also been evaluated by HR-ARM previously. Rectoanal pressures were assessed at rest, during squeeze and simulated evacuation. Concordance among pressures was assessed with Lin's concordance correlation coefficient (CCC). KEY RESULTS: Anal resting and squeeze pressures measured with HD-ARM were reproducible on the same and different days; for average resting pressures of HD-ARM1 vs HD-ARM2, CCC = 0.73 (95% confidence interval [CI]: 0.53-0.94), and for HD-ARM1 vs HD-ARM3, CCC = 0.60 (95% CI: 0.28-0.93). For maximum squeeze pressures of HD-ARM1 vs HD-ARM2, CCC = 0.86 (95% CI: 0.75-0.97), and for HD-ARM1 vs HD-ARM3, CCC = 0.56 (95% CI: 0.21-0.91). The rectoanal gradient during evacuation was significantly concordant between HD-ARM1 and HD-ARM2 but not HD-ARM1 and HD-ARM3. Resting (CCC = 0.38 [95% CI: 0.14-0.62]) and squeeze pressures (CCC = 0.73 [95% CI: 0.57-0.89]) measured with HD-ARM1 and HR-ARM were also concordant. CONCLUSIONS & INFERENCES: Among women with fecal incontinence, measurements with HD-ARM were reproducible on the same (anal resting and squeeze pressures and rectoanal gradient during evacuation) and different days (anal resting and squeeze pressures) and correlated with HR-ARM measurements. These findings support use of HD-ARM and HR-ARM for longitudinal assessments of anal resting and squeeze pressures.

Opioid analgesic use among patients presenting with acute abdominal pain and factors associated with surgical diagnoses.

BACKGROUND: The prevalence of chronic opioid use among non-cancer patients presenting with acute abdominal pain (AAP) is unknown. The aim was to characterize opioid use, constipation, diagnoses, and risk factors for surgical diagnoses among non-cancer patients presenting with AAP to an emergency department (ED). METHODS: We performed a retrospective, observational cohort study of all (n=16,121) adult patients (88% from MN, IA and WI) presenting during 2014 with AAP. We used electronic medical records, and focused on 2352 adults with AAP who underwent abdominal CT scan within 24 hours of presentation. We determined odds ratios of association with constipation and features predicting conditions that may require surgery (surgical diagnosis). KEY RESULTS: There were 2352 eligible patients; 18.8% were opioid users. Constipation was more frequent in opioid (35.1%) compared to non-opioid users [OR 2.88 (95% CI 2.28, 3.62)]. Prevalence of surgical diagnosis in the opioid and non-opioid users was 35.3% and 41.7% respectively (P=.019). By univariate analysis, age and neutrophil count independently predicted increased risk, and chronic opioid use decreased risk of surgical diagnosis. Internal validation of logistic models using a randomly selected validation subset (25% of entire cohort, 587/2352) showed receiver operating characteristic (ROC) curves for the validation and full cohorts were similar. CONCLUSIONS AND INFERENCES: Approximately 19% of adults presenting with AAP were opioid users; constipation is almost three times as likely in opioid users compared to non-opioid users presenting with AAP. Factors significantly associated with altered risk of surgical diagnoses were age, opioid use, and neutrophil count.

Creation of a model to predict survival in patients with refractory coeliac disease using a multinational registry.

BACKGROUND: Refractory coeliac disease is a severe complication of coeliac disease with heterogeneous outcome. AIM: To create a prognostic model to estimate survival of patients with refractory coeliac disease. METHODS: We evaluated predictors of 5-year mortality using Cox proportional hazards regression on subjects from a multinational registry. Bootstrap resampling was used to internally validate the individual factors and overall model performance. The mean of the estimated regression coefficients from 400 bootstrap models was used to derive a risk score for 5-year mortality. RESULTS: The multinational cohort was composed of 232 patients diagnosed with refractory coeliac disease across seven centres (range of 11-63 cases per centre). The median age was 53 years and 150 (64%) were women. A total of 51 subjects died during a 5-year follow-up (cumulative 5-year all-cause mortality = 30%). From a multiple variable Cox proportional hazards model, the following variables were significantly associated with 5-year mortality: age at refractory coeliac disease diagnosis (per 20 year increase, hazard ratio = 2.21; 95% confidence interval, CI: 1.38-3.55), abnormal intraepithelial lymphocytes (hazard ratio = 2.85; 95% CI: 1.22-6.62), and albumin (per 0.5 unit increase, hazard ratio = 0.72; 95% CI: 0.61-0.85). A simple weighted three-factor risk score was created to estimate 5-year survival. CONCLUSIONS: Using data from a multinational registry and previously reported risk factors, we create a prognostic model to predict 5-year mortality among patients with refractory coeliac disease. This new model may help clinicians to guide treatment and follow-up.

Effects of hemin on heme oxygenase-1, gastric emptying, and symptoms in diabetic gastroparesis.

BACKGROUND: Therapeutic options for management of diabetic gastroparesis are limited. Failure to maintain upregulation of heme oxygenase (HO1) leads to loss of interstitial cells of Cajal and delayed gastric emptying (GE) in non-obese diabetic mice. Our hypothesis was that hemin upregulation of HO1 would restore normal GE in humans with gastroparesis. AIMS: To compare effects of hemin and placebo infusions on HO1 activity and protein, GE, autonomic function, and gastrointestinal symptoms in diabetic gastroparesis. METHODS: In a single-center, double-blind, placebo-controlled, randomized clinical trial, we compared intravenous hemin, prepared in albumin, or albumin alone (placebo) in 20 patients, aged 41 ± 5 (SEM) years with diabetic gastroparesis. After infusions on days 1, 3, and 7, weekly infusions were administered for 7 additional weeks. Assessments included blood tests for HO1 protein and enzyme activity levels, GE with 13 C-spirulina breath test, autonomic functions (baseline and end), and gastrointestinal symptoms every 2 weeks. KEY RESULTS: Nine of 11 patients randomized to hemin completed all study procedures. Compared to placebo, hemin increased HO1 protein on days 3 (p = 0.0002) and 7 (p = 0.008) and HO1 activity on day 3 (p = 0.0003) but not after. Gastric emptying, autonomic functions, and symptoms did not differ significantly in the hemin group relative to placebo. CONCLUSIONS & INFERENCES: Hemin failed to sustain increased HO1 levels beyond a week and did not improve GE or symptoms in diabetic gastroparesis. Further studies are necessary to ascertain whether more frequent hemin infusions or other drugs would have a more sustained effect on HO1 and improve GE.

The incidence rate and characteristics of clinically diagnosed defecatory disorders in the community.

BACKGROUND: Defecatory disorders (DD) are defined by clinical and objective features of impaired rectal evacuation. The epidemiology of DD in the population is unknown, partly because many constipated patients do not undergo anorectal tests. Our objectives were to estimate the incidence rate and clinical features of DD in the community. METHODS: We reviewed the medical records of all patients older than 16 years in Olmsted County, MN, who had constipation and underwent anorectal manometry from 1999 through 2008. Criteria for diagnosing DD were constipation for 6 months or longer and one of the following: (i) abnormal rectal balloon expulsion test; (ii) reduced or increased perineal descent; or (iii) two or more abnormal features with defecography or surface electromyography. KEY RESULTS: Of 11 112 constipated patients, 516 had undergone anorectal tests; 245 of these (209 women, 36 men) had a DD. The mean (±SD) age at diagnosis was 44 years (±18) among women and 49 years (±19) among men. The overall age- and sex-adjusted incidence rate per 100 000 person-years was 19.3 (95% CI: 16.8-21.8). The age-adjusted incidence per 100 000 person-years was greater (p < 0.0001) in women (31.8, 95% CI: 27.4-36.1) than in men (6.6, 95% CI: 4.4-8.9). Prior to the diagnosis of DD, nearly 30% of patients had irritable bowel syndrome (IBS), 48% had a psychiatric diagnosis, 18% had a history of abuse, and 21% reported urinary and/or fecal incontinence. CONCLUSIONS & INFERENCES: Among constipated patients, DD are fourfold more common in women than men and often associated with IBS and psychiatric diagnoses.

Irritable bowel syndrome and the perinatal period: lower birth weight increases the risk.

BACKGROUND: Early life events have been found to be associated with irritable bowel syndrome (IBS) suggesting a role in development of functional disorders. The study aim was to identify potential perinatal risk factors for adult IBS. METHODS: Utilizing a population-based nested case-control design, cases who met modified Rome III criteria for IBS and age- and-gender matched controls were identified using responses from prior mailed surveys to a random sample of Olmsted County residents. Medical records of eligible respondents were reviewed for perinatal events of interest. The association of early life events with subsequent case status was assessed using conditional logistic regression. KEY RESULTS: Of 3 417 respondents, 513 were born in Olmsted County and 108 met criteria for IBS. Due to missing records, 89 pairs were included in the final analyses. Logistic regression revealed only birth weight as a predictor of IBS. Lower birth weight increased the odds for IBS (OR = 1.54 [95% CI = (1.12, 2.08), p = 0.008]). Median birth weight was 3.35 kg (range: 1.96-5.24) and 3.57 kg (range: 2.18-4.59) for cases and controls, respectively. Maternal age, delivery method, and antibiotic exposure were not associated with IBS status but this study was only powered to detect large odds ratios. CONCLUSIONS AND INFERENCES: Lower birth weight was observed as a risk factor for IBS. It is not clear if in utero developmental delays directly lead to IBS or if low birth weight is a prospective marker for subsequent early life problems leading to IBS.

Determinants and clinical impact of pressure drift in manoscan anorectal high resolution manometry system.

BACKGROUND: Pressure drift (PD), resulting from differences between room and body temperature, reduces the accuracy of pressure measurements with the Manoscan high resolution manometry (HRM) system. Our aims were to assess PD during anorectal HRM. METHODS: Defined as the residual pressure measured immediately after the catheter was removed, PD was calculated for each sensor and averaged across all 12 sensors in 454 anorectal consecutive studies recorded with 3 HRM catheters. The relationship between PD and study duration, number of prior uses of a catheter, and peak and average pressure exposure during a study were evaluated. The correction of PD with a software algorithm (thermal compensation) was evaluated in 76 studies where the most distal sensor was outside the body. KEY RESULTS: The PD varied among sensors and across catheters. The average PD (7.3 ± 0.2 mmHg) was significantly greater for newer catheters, during longer studies, or when sensors were exposed to higher pressures. Together, these factors explained 81% of the variance in overall PD. After thermal compensation, the uncorrected median PD for the most distal sensor was 2.5-5 mmHg over the study duration. Correcting this changed the interpretation (e.g., as abnormal instead of normal) of at least 1 anorectal parameter in eight of 76 studies. CONCLUSIONS & INFERENCES: During anorectal HRM, PD declines with catheter use and is greater for newer catheters, when sensors are exposed to higher pressures, and for studies of longer duration. While PD is partially corrected with thermal compensation algorithms, the impact on interpretation is modest.

Validating endpoints for therapeutic trials in fecal incontinence.

BACKGROUND: A 50% or greater reduction in the frequency of fecal incontinence (FI) recorded with daily bowel diaries is the primary endpoint in clinical trials of FI. Whether this difference is clinically important is unknown. The relationship between FI symptoms recorded with daily and weekly instruments is unknown. The contribution of psychological factors to quality of life (QOL) in FI is unclear. METHODS: Fecal incontinence severity was assessed with daily bowel diaries and periodic questionnaires (fecal incontinence severity score [FISS], FIQOL, 36-Item Short Form Health Survey [SF-36], and hospital anxiety and depression scales) for 4 weeks before and during double-blind randomization to placebo or clonidine in 44 women with FI. The reduction in FI frequency was compared to the minimal clinically important difference (MCID) computed from the FISS. Endpoints of FI were compared between daily and weekly diaries. KEY RESULTS: The FISS exceeded the MCID in 75% and 83% of patients in whom the FI frequency declined by 50-74% and ≥75% respectively. Parameters of FI measured with daily and weekly instruments were significantly correlated. The daily parameters explained 71% of the inter-patient variation in the FISS. The SF-36 health scores, rather than the FISS rating, explained a majority of the inter-subject variation in FIQOL. CONCLUSIONS & INFERENCES: Most patients who report a ≥50% reduction in FI frequency experience a clinically important improvement. Weekly questionnaires accurately assess the severity of FI. Self-reported physical and mental health explained a greater proportion of the variance in FIQOL than FI symptom severity.

Effect of neostigmine on gastroduodenal motility in patients with suspected gastrointestinal motility disorders.

BACKGROUND: Acetylcholinesterase inhibitors (ACIs), e.g., neostigmine, are known to increase upper and lower gastrointestinal (GI) motility and are used to treat acute colonic pseudoobstruction. However, their effects on gastroduodenal motility in humans are poorly understood. Our hypotheses were that, in patients with suspected GI motility disorders, neostigmine increases gastric and small intestinal motor activity, and these effects are greater in patients with cardiovagal neuropathy, reflecting denervation sensitivity. METHODS: In this open label study, the effects of neostigmine (1 mg intravenously) on gastroduodenal motor activity recorded with manometry were assessed in 28 patients with a suspected GI motility disorder. Cardiovagal function was assessed with the heart rate response to deep breathing and GI transit by scintigraphy. KEY RESULTS: The final diagnoses were gastroparesis (6 patients), gastroparesis with intestinal neuropathy (3 patients), intestinal neuropathy or pseudoobstruction (5 patients), functional dyspepsia (6 patients), chronic abdominal pain (3 patients), mechanical small intestinal obstruction (3 patients), and pelvic floor dysfunction (2 patients). Neostigmine increased both antral and intestinal phasic pressure activity (p < 0.001). Neostigmine increased antral and intestinal pressure activity in 81% and 50% of patients with reduced postprandial antral and intestinal contractile responses to meal, respectively. The antroduodenal pressure response to neostigmine was not higher in patients with cardiovagal dysfunction. CONCLUSIONS & INFERENCES: Neostigmine increased antral and intestinal motor activity in patients with hypomotility, including intestinal dysmotility. These responses to neostigmine were not greater in patients with cardiovagal dysfunction. The use of longer-acting ACIs for treating antroduodenal dysmotility warrant further study.

A novel technique for bedside anorectal manometry in humans.

BACKGROUND: Currently, anorectal manometry (ARM), which is used to diagnose defecatory disorders and identify anal weakness in fecal incontinence (FI) is generally conducted in specialized laboratories. Our aims were to compare anorectal functions measured with high-resolution manometry (HRM) and a novel portable manometry device. METHODS: Anal pressures at rest, during squeeze, and simulated evacuation, and rectal sensation were evaluated with portable and HRM in 20 healthy women, 19 women with constipation, and 11 with FI. The relationship between anal pressures measured with portable and HRM was assessed by the concordance correlation coefficient (CCC), Bland Altman test, and paired t-tests. KEY RESULTS: Anal pressures at rest (CCC 0.45; 95% CI: 0.29, 0.58) and during squeeze (CCC 0.60; 95% CI: 0.46, 0.72) measured with portable and HRM were correlated and inversely associated with the risk of FI. During simulated evacuation, the CCC for rectal pressure (0.62; 95% CI: 0.43, 0.76) was greater than that for anal pressure (CCC 0.22; 95% CI: 0.04, 0.39) and the rectoanal gradient (CCC 0.22; 95% CI: 0.02, 0.41). Rectal sensory thresholds for first sensation, the desire to defecate, and urgency measured by portable and HRM were also significantly correlated between techniques. For several parameters, differences between portable and HRM were statistically significant and the Bland Altman test was positive. CONCLUSIONS & INFERENCES: Anorectal pressures and rectal sensation can be conveniently measured by portable manometry and are significantly correlated with high-resolution manometry.

Non-enteric infections, antibiotic use, and risk of development of functional gastrointestinal disorders.

BACKGROUND: Gastrointestinal infections are risk factors for irritable bowel syndrome (IBS) and functional dyspepsia (FD). We investigated whether non-enteric infections and antibiotic exposure are also associated with the development of functional gastrointestinal disorders (FGIDs). METHODS: In a nested case-control study, random samples of Olmsted County, MN, were mailed valid self-report questionnaires from 1988 through 1994, and then follow-up questionnaires from 1995 through 2003. Survey responders who did not report any FGID symptoms at baseline, but then reported such symptoms in at least one subsequent survey, were classified as new-onset cases. Age-matched controls were individuals who did not have symptoms at either the initial or subsequent surveys. KEY RESULTS: The overall response rate was 78% to the initial survey and 52% to the follow-up survey. Based on the responses, 316 participants had a new onset of an FGID (43 IBS constipation, 95 IBS diarrhea, 25 IBS mixed, and 153 other FGIDs, including FD) and 250 did not (controls). Around 76% (241/316) of cases reported a non-enteric infection vs 66% (166/250) of the controls. The frequency of enteric infections was similar between the two groups. Of the new FGID cases, 83% had a non-enteric infection that was treated with antibiotic. In a logistic regression model, treatment with antibiotics for a non-gastrointestinal infection was associated with the development of an FGID (odds ratio = 1.90; 95% CI: 1.21-2.98; p = 0.005), after adjusting for age and sex. CONCLUSIONS & INFERENCES: Based on a case-control study, treatment of a non-gastrointestinal infection with antibiotics appears to be a risk factor for development of an FGID.

Effect of colesevelam on faecal bile acids and bowel functions in diarrhoea-predominant irritable bowel syndrome.

BACKGROUND: About one-third of patients with IBS-diarrhoea (irritable bowel syndrome-D) have evidence of increased bile acid synthesis or excretion. AIMS: To assess effects of the bile acid sequestrant, colesevelam, on faecal excretion of BAs, hepatic BA synthesis and diarrhoea in IBS-D; to appraise whether individual or random stool samples accurately reflect 48-h total faecal bile acid excretion and proportions of the main bile acids excreted and to study the faecal fat excretion in response to colesevelam. METHODS: A single-centre, unblinded, single-dose trial of effects of colesevelam, 1875 mg [3 tablets (625 mg tablets)] orally, twice daily, for 10 days on total 48-h faecal bile acid excretion and fasting serum C4 (7α-hydroxy-4-cholesten-3-one; surrogate of hepatic bile acid synthesis). Stool diaries documented bowel functions for 8 days prior and 8 days during colesevelam treatment. Stool 48-h samples and fasting serum were collected for faecal fat, faecal bile acid and serum C4. RESULTS: Colesevelam was associated with significantly increased faecal total bile acid excretion and deoxycholic acid excretion, increased serum C4 and more solid stool consistency. There was a significant inverse correlation between number of bowel movements per week and the total bile acid sequestered into stool during the last 48 h of treatment. Random stool samples did not accurately reflect 48-h total or individual faecal bile acid excretion. Sequestration of bile acids by colesevelam did not increase faecal fat. CONCLUSIONS: Colesevelam increases delivery of bile acids to stool while improving stool consistency, and increases hepatic bile acid synthesis, avoiding steatorrhoea in patients with IBS-D. Overall effects are consistent with luminal bile acid sequestration by colesevelam.

Prevalence and risk factors for dysphagia: a USA community study.

BACKGROUND: Dysphagia is considered an alarm symptom but detailed population-based data on dysphagia are lacking. We aimed to estimate in a representative USA Caucasian population, the prevalence of dysphagia and potential risk factors. METHODS: A modified version of the previously validated Bowel Disease Questionnaire was mailed to a population-based cohort (n = 7640) of Olmsted County, MN. Dysphagia was measured by one validated question 'In the last year, how often have you had difficulty swallowing (a feeling that food sticks in your throat or chest)?' The medical records were reviewed for organic causes of dysphagia. The associations of reported frequency of dysphagia with potential risk factors were assessed using logistic regression models. KEY RESULTS: The sex-specific, age-adjusted (US White 2000) prevalence for dysphagia experienced at least weekly was 3.0% (95% CI: 2.2, 3.7) in females and 3.0% (95% CI: 2.0, 4.0) in males. Those with frequent heartburn (OR = 5.9 [4.0, 8.6]) and acid regurgitation (OR = 10.6 [6.8, 16.6]) were significantly more likely to report frequent dysphagia. Proton pump inhibitor (PPI) use was significantly associated with frequent (3.1, 95% CI 2.2, 4.4) and infrequent dysphagia (1.5, 955 CI 1.3, 1.8). Gastro-esophageal reflux disease (GERD) was the most common diagnosis in those reporting dysphagia on the medical record; other organic explanations were rare and only found in the frequent dysphagia group. CONCLUSIONS & INFERENCES: Frequent dysphagia is not rare in the community (3%), occurs in both women and men across all adult age groups, and is most likely to indicate underlying GERD.

Disturbances of gastrointestinal transit and autonomic functions in postural orthostatic tachycardia syndrome.

BACKGROUND: Gastrointestinal symptoms are common in the postural orthostatic tachycardia syndrome (POTS). However, few studies have evaluated gastrointestinal transit in POTS. Our primary objectives were to evaluate gastrointestinal emptying and the relationship with autonomic dysfunctions in POTS. METHODS: We reviewed the complete medical records of all patients aged 18 years and older with POTS diagnosed by a standardized autonomic reflex screen who also had a scintigraphic assessment of gastrointestinal transit at Mayo Clinic Rochester between 1998 and 2012. Associations between specific gastric emptying and autonomic (i.e., cardiovagal, adrenergic, and sudomotor) disturbances were evaluated. KEY RESULTS: Among 163 patients (140 women, mean [± SEM] age 30 [± 1] years), 55 (34%) had normal, 30 (18%) had delayed, and 78 (48%) had rapid gastric emptying. Fifty-eight patients (36%) had clinical features of physical deconditioning, which was associated (p = 0.02) with rapid gastric emptying. Associations with delayed gastric emptying included vomiting, which was more common (p < 0.003), and anxiety or depression, which was less common (p = 0.02). The tilt-associated increase in heart rate and reduction in systolic BP at 1 min was associated (p < 0.05), being greater in patients with delayed gastric emptying. CONCLUSIONS & INFERENCES: Two-thirds of patients with POTS and GI symptoms had abnormal, most frequently rapid gastric emptying. Except for more severe adrenergic impairment in patients with delayed gastric emptying, the pattern of autonomic dysfunction did not discriminate among gastric emptying groups. Further studies are necessary to ascertain whether extravascular volume depletion and/or deconditioning contribute to POTS in patients with gastrointestinal symptoms.