Systematic Review and Meta-analysis: Efficacy of Mesalamine in Irritable Bowel Syndrome.

BACKGROUND & AIMS: Some patients with irritable bowel syndrome (IBS) demonstrate low-grade inflammation in the intestine. Mesalamine, which has anti-inflammatory effects, may be an efficacious treatment for IBS, but studies are conflicting. We conducted a systematic review and meta-analysis to assess efficacy and safety of mesalamine in IBS. METHODS: We searched the medical literature up to September 14, 2022, to identify randomized controlled trials (RCTs) of mesalamine in IBS. We judged efficacy and safety using dichotomous assessments of effect on global IBS symptoms, abdominal pain, bowel habit or stool frequency, and occurrence of any adverse event. We pooled data using a random effects model, with efficacy and safety reported as pooled relative risks (RRs) with 95% confidence intervals (CIs). RESULTS: We identified 8 eligible RCTs (820 patients). Mesalamine was more efficacious than placebo for global IBS symptoms (RR of global symptoms not improving, 0.86; 95% CI, 0.79-0.95; number needed to treat = 10; 95% CI, 6-27), but not for abdominal pain or bowel habit or stool frequency. Subgroup analyses demonstrated efficacy of mesalamine in IBS with diarrhea for global IBS symptoms (RR, 0.88; 95% CI, 0.79-0.99), but not patients with other predominant bowel habits or those with post-infection IBS. Adverse event rates were no higher with mesalamine (RR, 1.20; 95% CI, 0.89-1.63) but were reported in only 5 trials. CONCLUSIONS: Mesalamine may be modestly efficacious for global symptoms in IBS, particularly IBS with diarrhea, but quality of evidence was low. Adequately powered high quality RCTs of mesalamine in IBS are needed.

Randomized, Double-Blind Placebo-Controlled Trial to Assess the Effect of Probiotics on Irritable Bowel Syndrome in Veterans With Gulf War Illness.

Background: Many veterans who served in Operation Desert Storm (August 1990 to March 1991) experienced a complex of symptoms of unknown etiology called Gulf War illness (GWI), which significantly impacts the health and quality of life (QOL) and may have contributed to irritable bowel syndrome (IBS). Methods: We performed a prospective, double-blind placebocontrolled study to determine the efficacy of the multistrain De Simone Formulation probiotic containing 8 strains of bacteria on symptoms of IBS and GWI. Veterans of Operation Desert Storm who had IBS and ≥ 2 nonintestinal symptoms of GWI were included. The primary study endpoint was change in bowel symptom score. The secondary endpoints were mean change in symptoms, QOL, and extra-intestinal and posttraumatic stress disorder (PTSD) symptoms. Results: A total of 101 Gulf War veterans with IBS and GWI were screened at the Veteran Affairs Medical Center in Salt Lake City, Utah. The study was completed by 53 veterans; 47 (89%) were male with a mean (SD) age of 55 (8) years. The probiotic did not improve IBS symptoms or other extra-intestinal symptoms common to IBS and GWI. Conclusions: Our study did not demonstrate statistically significant improvement in IBS symptoms or QOL after treatment with the probiotic. We also did not find any improvement in symptoms of GWI or PTSD.

Risk factors for upper and lower functional gastrointestinal disorders in Persian Gulf War Veterans during and post-deployment.

BACKGROUND: Gastroenteritis is a risk factor for irritable bowel syndrome (IBS), but its role in other functional gastrointestinal disorders (FGIDs) is less clear. The aim of this study was to determine the prevalence of FGIDs in Gulf War (GW) Veterans before, during, and after deployment and to determine whether gastroenteritis was a risk factor for upper and lower FGIDs. METHODS: The Veterans who served during the Persian GW were mailed validated questionnaires inquiring about their bowel habits, psychological and extra-intestinal symptoms, and quality of life (QOL). The lactulose hydrogen breath test (LBT) was performed for small intestinal bacterial overgrowth. KEY RESULTS: Data were analyzed from 468 GW Veterans. The prevalence of FGID before, during, and 16 years after deployment was 15.7%, 49.9%, and 64.2%, respectively. New FGIDs during deployment was reported by 41.2%, and during 16 years after deployment, 43.7% acquired new FGIDs. FGIDs were associated with psychological disorders, extra-intestinal symptoms, and lower QOL. Gastroenteritis was reported by 44.3% of deployed Veterans and was a risk factor for IBS, dyspepsia, and functional diarrhea post-deployment. The cases and controls did not differ significantly in the frequency of positive LBT. CONCLUSIONS AND INFERENCES: There is an increase in the prevalence of FGIDs during deployment, and it persists after deployment. There is a further increase in the prevalence of FGIDs after deployment. In addition to IBS, gastroenteritis during deployment is a risk factor for dyspepsia and functional diarrhea post-deployment. Therefore, prevention of gastroenteritis during deployment and screening of Veterans for FGIDs post-deployment would be of value for Veterans' long-term health.

Double-Blind Placebo-Controlled Study of Rifaximin and Lactulose Hydrogen Breath Test in Gulf War Veterans with Irritable Bowel Syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) occurs in up to 33% of Gulf War (GW) Veterans. Alterations in gut microflora including small intestinal bacterial overgrowth (SIBO) during deployment may play a role in development of IBS. Rifaximin is a minimally absorbed antibiotic speculated to improve IBS symptoms, in part, by restoring normal gut microflora. The aim of this study was to compare rifaximin to placebo on IBS symptoms and quality of life (QOL) in GW Veterans with IBS without constipation. METHODS: A double-blind, placebo-controlled study was performed. One hundred and twenty-two GW Veterans with IBS (Rome III) from our database and referral to gastroenterology and internal medicine clinics were screened. After a 2-week run-in period, 50 patients were randomized (1:1) to receive either rifaximin 550 gm or placebo twice daily for 2 weeks in a double-blind study. Patients were advised not to change their diet or medications during the study. The symptoms assessed were: (1) stool frequency, (2) stool consistency (Bristol stool scale, 1-7, very hard to watery), (3) urgency (1 = yes/0 = no daily for 7 days), (4) severity of abdominal pain (0-4, none to severe), (5) severity of bloating (1-4, none to severe), and (6) global improvement scale (1-7, substantially worse to substantially improved). These were recorded for 7 consecutive days and then averaged across the 7 days, to generate a continuous variable. The symptom data were compared after 2 weeks of treatment. QOL was assessed using IBS-QOL. The lactulose hydrogen breath test (LHBT) was performed at baseline and after 2 weeks of treatment. RESULTS: Fifty Veterans were randomized to receive treatment; 3 withdrew and 3 were lost to follow-up. Data were analyzed from 44 patients (38 men, 6 women, median age 52, range 33-77 years). Rifaximin was not associated with significant improvement in global symptoms, abdominal pain, bloating, stool urgency, frequency, or consistency (all P ≥ 0.25) or QOL (all P ≥ 0.26). Normalization of SIBO by LHBT was not different between rifaximin- and placebo-treated Veterans (7 vs. 22%, P = 0. 54). CONCLUSION: Rifaximin was not effective in improving IBS symptoms and QOL in GW Veterans with non-constipated IBS.

Investigating Clinical Benefits of a Novel Sleep-Focused Mind-Body Program on Gulf War Illness Symptoms: A Randomized Controlled Trial.

OBJECTIVE: Mind-Body Bridging (MBB) has been shown to be effective for improving disturbed sleep. In this prospective randomized controlled trial, we evaluated the efficacy of sleep-focused MBB compared with sleep education control (SED) for improving sleep in previously deployed Gulf War veterans. METHODS: US military service members with sleep and physical health complaints who were deployed in 1990-1991 were randomized to receive three weekly sessions of either MBB (n = 33) or SED (n = 27) between 2012 and 2015. The primary outcome of Medical Outcomes Study Sleep Scale was completed at baseline, weekly during treatment, postintervention, and 3-month follow-up. Secondary outcome measures for posttraumatic stress disorder, depression, fatigue, quality of life, symptom severity, and mindfulness were completed at baseline, postintervention and 3-month follow-up. Salivary samples were collected at five time points per day at each visit for cortisol and α-amylase assessment. Clinician-administered assessments of sleep and co-occurring conditions were conducted at baseline and postintervention. RESULTS: MBB was significantly more efficacious than SED in reducing disturbed sleep at follow-up (F(1,180.54) = 4.04, p = .046). In addition, self-reported posttraumatic stress disorder (F(1,56.42) = 4.50, p = .038) for the treatment effect, depression (F(1,93.70) = 4.44, p = .038), and fatigue symptoms (F(1,68.58) = 3.90, p = .050) at follow-up improved in MBB compared with those in SED. Consistently higher percentages of veterans in MBB reported improvements of sleep, pain, and composite sleep/general co-occurring symptoms at the postclinical evaluation, as compared with veterans in SED. Finally, the mean waking level of salivary α-amylase in the MBB declined to a greater extent than that in the SED, at follow-up (F(1,88.99) = 3.78, p = .055), whereas no effects were found on cortisol. CONCLUSIONS: Sleep-focused MBB can improve sleep and possibly also co-occurring symptoms in Gulf War veterans. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT01543997.

Overexpression of mutant amyloid-ß protein precursor and presenilin 1 modulates enteric nervous system.

Alzheimer's disease (AD) is a neurodegenerative disorder histologically characterized by amyloid-ß (Aß) protein accumulation and activation of associated microglia. Although these features are well described in the central nervous system, the process and consequences of Aß accumulation in the enteric nervous system have not been extensively studied. We hypothesized that Aß also may accumulate in the enteric nervous system and lead to immune cell activation and neuronal dysfunction in the digestive tract not unlike that observed in diseased brain. To test this hypothesis, ileums of the small intestine of thirteen month old AßPP/PS1 and C57BL/6 (wild type) mice were collected and analyzed using immunohistochemistry, western blot analysis, cytokine arrays, and ELISA. AßPP/PS1 mice demonstrated no differences in intestinal motility or water absorption but elevated luminal IgA levels compared to wild type mice. They also had increased protein levels of AßPP and the proteolytic enzyme, BACE, corresponding to an increase in Aß1-40 in the intestinal lysate as well as an increase in both Aß1-40 and Aß1-42 in the stool. This correlated with increased protein markers of proinflammatory and immune cell activation. Histologic analysis localized AßPP within enteric neurons but also intestinal epithelial cells with elevated Aß immunoreactivity in the AßPP/PS1 mice. The presence of AßPP, Aß, and CD68 immunoreactivity in the intestines of some patients with neuropathologically-confirmed AD are consistent with the findings in this mouse model. These data support the hypothesis that in AD the intestine, much like the brain, may develop proinflammatory and immune changes related to AßPP and Aß.

Double-blind placebo-controlled study of mesalamine in post-infective irritable bowel syndrome--a pilot study.

OBJECTIVE: Post-infective irritable bowel syndrome (PI-IBS) is characterized by continuing symptoms of irritable bowel syndrome, typically diarrhea-predominant, following an episode of acute gastroenteritis. There is often an increase in sub-epithelial inflammatory and neuroendocrine cells on colonic mucosal biopsy. Mesalamine is an anti-inflammatory agent, effective in the treatment of inflammatory bowel disease. The goal of this study was to compare mesalamine to placebo on symptoms and quality-of-life (QOL) in PI-IBS. MATERIAL AND METHODS: Twenty patients who developed diarrhea-predominant IBS after gastroenteritis were randomized to receive mesalamine (Asacol®) 1.6 gm b.i.d. or placebo for 12 weeks in a double-blind placebo-controlled study. QOL was assessed using the IBS-QOL questionnaire. Stool frequency, stool consistency, urgency, severity of abdominal pain, severity of bloating, and global-improvement scale were recorded in daily diaries for 7 days at baseline and every 4 weeks. Data were analyzed by comparing the change from baseline to last follow-up. RESULTS: One patient withdrew after randomization; data were incomplete in two patients. Thus, data were analyzed from 17 patients (11 men and 6 women, median age: 27 years, range 22-45 years). Mesalamine was not associated with significant improvement in global symptoms, abdominal pain, bloating, stool urgency, frequency, or consistency (all p ≥ 0.11) or QOL (p ≥ 0.16). CONCLUSIONS: There was no significant improvement in global symptoms or overall QOL with mesalamine in patients with PI-IBS.

Lubiprostone for constipation and irritable bowel syndrome with constipation.

Chronic constipation and irritable bowel syndrome are heterogeneous disorders characterized by altered bowel habits, abdominal discomfort and/or difficult defecation. These conditions have a significant impact on patients' quality of life, as well as on the US economy, both in terms of healthcare costs and lost productivity. Treatment typically begins with lifestyle changes, increased fiber intake and osmotic and stimulant laxative intake. However, treatments for constipation vary in terms of their efficacy and safety. Furthermore, surveys of physicians and patients have revealed a strong desire for improved therapeutic options. Lubiprostone is a synthetic bicyclic fatty acid that is gut selective and stimulates type 2 chloride channels, resulting in increased chloride, sodium and water secretion into the lumen. The increased fluid secretion causes luminal distension, secondary peristalsis and laxation. Randomized Phase III trials have shown that lubiprostone is efficacious in the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation. The US FDA has approved lubiprostone at a dose of 24 microg twice daily for the treatment of chronic idiopathic constipation in adults, and at a dose of 8 microg twice daily for irritable bowel syndrome with constipation in adult women. Nausea, diarrhea and headaches are the most commonly reported side effects. In long-term studies, lubiprostone appears to be safe.

Abdominal bloating in employed adults: prevalence, risk factors, and association with other bowel disorders.

UNLABELLED: BACKGROUND Bloating is common, but its significance as a marker of underlying disease has not been defined. AND AIMS: We report on risk factors for bloating, its relationship to physical activity and quality of life (QOL), and its predictive value for functional bowel disorders. METHODS: This is a cross-sectional population-based study of 1,069 employees of the Veterans Affairs Black Hills Health Care System. The validated Bowel Disease Questionnaire was used to identify subjects with abdominal bloating and other bowel disorders. The association of bloating with QOL was assessed using the SF36 (Short-Form 36) questionnaire. Physical activity was assessed using the modified Baecke questionnaire. RESULTS: The response rate was 72% (723 of 1,069). Bloating was reported by 21% of all subjects (95% confidence interval [CI] 17.7-23.7), 64% with irritable bowel syndrome (IBS), 35% with non-IBS constipation, 23% with non-IBS diarrhea, and 42% with dyspepsia. Functional bloating (i.e., bloating in the absence of other bowel disorders) was reported by 7% of subjects (95% CI 5.2-9.0). Of those with bloating, 28% had IBS, 25% non-IBS constipation, 8% non-IBS diarrhea, and 30% dyspepsia. The positive and negative predictive values of bloating in the diagnosis of functional bowel disorder were 66% and 87%, respectively. The only risk factors were smoking and high-dose aspirin. Bloating was not associated with physical activity. QOL on all subscales of SF36 was lower in subjects with bloating than those without bloating. CONCLUSIONS: Bloating is a common symptom in otherwise healthy adults, and is often associated with but not predictive of functional bowel disorders. Smoking and high-dose aspirin are associated with bloating while physical activity is not.

Development of functional diarrhea, constipation, irritable bowel syndrome, and dyspepsia during and after traveling outside the USA.

BACKGROUND: Persistent gastrointestinal (GI) symptoms after travel abroad may be common. It remains unclear how often subjects who developed new GI symptoms while abroad have persistent symptoms on return. The objective of this retrospective study was to evaluate the prevalence of persistent GI symptoms in a healthy cohort of travelers. METHODS: One hundred and eight consecutive patients, mostly returned missionaries, attending the University of Utah International Travel Clinic for any reason (but mostly GI symptoms) had data recorded about their bowel habits before, during, and after travel abroad. All subjects had standard hematological, biochemical, and microbiological tests to exclude known causes of their symptoms. Endoscopic procedures were performed when considered necessary by the treating physician. Diarrhea, constipation, irritable bowel syndrome (IBS), bloating, and dyspepsia were defined according to the Rome II Criteria. RESULTS: Eighty three (82% men and 18% women, median age 21 years) completed the survey with 68 subjects completing the questionnaire about bowel habits before and during travel. Among the respondents, 55 (82.1%) did not have any symptoms before travel. During travel, 41 (63%) developed new onset diarrhea; 6 (9%) developed constipation; 16 (24%) IBS, 29 (45%) bloating; and 11 (16%) dyspepsia. Of those who developed symptoms during travel, 27 (68%) had persistent diarrhea, 3 (50%) had persistent constipation, 10 (63%) had persistent IBS, 12 (43%) had persistent bloating and 8 (73%) had persistent dyspepsia. The presence of bowel symptoms during and after travel was not associated with age, gender, travel destination, or duration of travel. CONCLUSIONS: This study suggests that new onset of diarrhea, IBS, constipation, and dyspepsia are common among subjects traveling abroad. Gastrointestinal symptoms that develop during travel abroad usually persist on return.

Video capsule endoscopy compared with standard endoscopy for the evaluation of small-bowel polyps in persons with familial adenomatous polyposis (with video).

BACKGROUND: Video capsule endoscopy (VCE) may be useful for surveillance of small-bowel polyps in patients with familial adenomatous polyposis (FAP). OBJECTIVE: To compare VCE to standard endoscopy for diagnosing small-bowel polyps in a defined segment of small bowel (proximal to a tattoo) and the entire examined small bowel. DESIGN: Prospective. SETTING: Single tertiary referral center. PATIENTS: Participants with FAP (n = 32). The majority were selected for their high number of proximal small-bowel polyps and prior endoscopic tattoo placement in the proximal small bowel. INTERVENTIONS: VCE (interpreted by 2 readers), push enteroscopy (PE), and lower endoscopy (LE) to count and measure small-bowel polyps. RESULTS: In the defined segment, VCE detected a median of 10.0 (interquartile range [IQR], 5.0-19.0) and 9.0 (IQR, 6.0-16.0) polyps for each reader compared with a median of 41.0 (IQR, 19.0-64.0) polyps on PE (P = .002). Agreement between the 2 methods was fair (kappa = 0.34, 0.36). Agreement between VCE and PE was poor to fair (kappa = 0.10, 0.22) for estimating the size of the largest polyp and poor (kappa = -0.20, -0.27) for detecting large polyps (> or =1 cm). In the entire examined small bowel, VCE diagnosed a median of 38.0 (IQR, 10.5-71.5) and 54.0 (IQR, 13.0-100.0) polyps for each reader compared with a median of 123.0 (IQR, 38.5-183.0) for combination endoscopy (PE and LE) (P < .001). Agreement between the 2 methods was fair to moderate (kappa = 0.21, 0.56). LIMITATIONS: Participants selected for high polyp burden, and results may not be applicable to all patients with FAP. CONCLUSIONS: VCE underestimates the number of small-bowel polyps in persons with FAP and does not reliably detect large polyps.

Is constipation associated with decreased physical activity in normally active subjects?

BACKGROUND: The effectiveness of physical activity in the management of constipation remains controversial. We examined the associations among physical activity, constipation, and quality of life (QoL) in a population of employed adults to determine whether the risk of constipation is related to physical activity. METHODS: A total of 1,069 employees (age range 24-77) of the Veterans Affairs (VA) Black Hills Health Care System were mailed validated questionnaires (response rate 72%), inquiring about bowel habits, QoL (SF 36), and physical activity (modified Baecke questionnaire). Constipation was defined using the Rome I criteria. RESULTS: One hundred and forty (19.4%, 95% CI 16.2-22.4) employees reported constipation. The average total physical activity and all subscales of physical activity were not significantly different in subjects with and without constipation (all p > or = 0.2). Subjects with constipation had lower QoL scores than subjects without constipation, and physical activity was positively correlated with physical functioning and health perception. CONCLUSION: Physical activity appears to be unrelated to the risk of constipation in employed adults, but higher physical activity was associated with improved QoL. Recommendations to increase physical activity may not alter symptoms of constipation but may improve overall well-being.

Comparison of air-coupled balloon esophageal and anorectal manometry catheters with solid-state esophageal manometry and water-perfused anorectal manometry catheters.

Clinical gastrointestinal manometry studies are currently performed with multilumen water-perfused polyvinyl or strain gauge sensor solid-state catheters. A disposable catheter incorporating air-filled balloons has been developed with performance characteristics suitable for esophageal and anorectal manometry studies. Our aim was to compare esophageal and anorectal pressure measurements using this newly developed catheter with measurements obtained using standard solid-state or water-perfused catheters. Measurements of resting LES pressure, esophageal contraction amplitudes, and anorectal rest and squeeze pressures were obtained in 10 healthy volunteers using a solid-state esophageal catheter, a water-perfused anorectal catheter, and air-filled balloon esophageal and anorectal catheters. Correlation coefficient analysis demonstrated that LES pressures, esophageal contraction amplitudes, and anorectal resting and squeeze pressures were not significantly among between the different catheters. We conclude that recently developed air-filled balloon esophageal and anorectal manometry catheters provide very similar measurements of LES, esophageal body, and anorectal sphincter pressures compared to presently used manometry catheters.

Dyssynergic defecation: demographics, symptoms, stool patterns, and quality of life.

To understand the nature of bowel disturbance in patients with dyssynergia, we prospectively examined demographics, stool patterns, and quality of life by administering a 31-item questionnaire to 120 patients who fulfilled symptomatic and manometric criteria for dyssynergia (Rome II). Data from 118 subjects (M/F = 27/91) was analyzed. Eighty four percent of patients reported excessive straining, and 76% reported feeling of incomplete evacuation; 9.7% had no urge to defecate. Abdominal bloating was reported by 74%. More women than men reported infrequent bowel movements and need to strain excessively (P < 0.05). Forty eight percent of patients, more women (P < 0.05) than men used digital maneuvers to evacuate. Hard stools was reported by 60% of women and 41% of men. Sexual abuse was reported by 22%; 21% were women (P = 0.02). Physical abuse was reported by 32%. Bowel problem adversely affected family life in 33%, sexual life in 56%, work life in 69% and social life in 76% of patients. Most patients with dyssynergia reported an excessive need to strain, feeling of incomplete evacuation and abdominal bloating and one half used digital maneuvers. It significantly affected quality of life, particularly in women.