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Background and Aim: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with other somatic disorders. We studied the prevalence and predictors of fibromyalgia and chronic fatigue syndrome (CFS) in IBS patients. Methods: We used the National Inpatient Sample and included hospitalization of individuals with IBS, using ICD-10 codes, from 2016–2019. The prevalence and predictors of fibromyalgia and CFS in IBS patients were studied. Univariate and multivariate patient- and hospital-level regression models were used to calculate the adjusted odds of fibromyalgia and CFS in the IBS patient population. Results: Of 1,256,325 patients with an ICD-10 code of IBS included in the study, 10.73% (134,890) also had ICD-10 codes for fibromyalgia and 0.42% (5220) for CFS. The prevalence of fibromyalgia and CFS was significantly higher in IBS patients (adjusted odds ratio (AOR) 5.33, 95% confidence interval (CI) 5.24–5.41, p < 0.001, and AOR 5.40, 95% CI 5.04–5.78, p < 0.001, respectively) compared to the general adult population without IBS. IBS-diarrhea, IBS-constipation, and IBS-mixed types were independently associated with increased odds of fibromyalgia and CFS. Increasing age (AOR 1.02, 95% CI 1.01–1.04, p 0.003; AOR 1.02, 95% CI 1.01–1.03, p 0.001), female gender (AOR 11.2, 95% CI 11.1–11.4, p < 0.001; AOR 1.86, 95% CI 1.78–1.93, p < 0.001) and white race (AOR 2.04, 95% CI 1.95–2.12, p < 0.001; AOR 1.69, 95% CI 1.34–2.13, p < 0.001) were independent predictors of increased odds of fibromyalgia and CFS, respectively. Conclusions: It appears that IBS is associated with an increased prevalence of somatic disorders such as fibromyalgia and CFS. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS‐C) often experience severe symptoms. The current aim was to evaluate plecanatide in adults with CIC or IBS‐C with severe constipation. Methods: Data were analyzed post hoc from randomized, placebo‐controlled trials (CIC [n = 2], IBS‐C [n = 2]) of plecanatide 3 mg, 6 mg, or placebo administered for 12 weeks. Severe constipation was defined as no complete spontaneous bowel movements (CSBMs) and an average straining score ≥3.0 (CIC; 5‐point scale) or ≥8.0 (IBS‐C; 11‐point scale) during a 2‐week screening. Primary efficacy endpoints were durable overall CSBM responders (CIC: ≥3 CSBMs/week, plus increase from baseline of ≥1 CSBM/week, for ≥9 of 12 weeks, including ≥3 of the last 4 weeks) and overall responders (IBS‐C: ≥30% reduction from baseline in abdominal pain and ≥1 CSBM/week increase for ≥6 of 12 weeks). Key Results: Severe constipation was observed in 24.5% (646/2639) and 24.2% (527/2176) of CIC and IBS‐C populations, respectively. The CIC durable overall CSBM response rate (plecanatide 3 mg, 20.9%; plecanatide 6 mg, 20.2%; placebo, 11.3%) and IBS‐C overall response rate (plecanatide 3 mg, 33.0%; plecanatide 6 mg, 31.0%; placebo, 19.0%) were significantly greater with plecanatide versus placebo (p ≤ 0.01 for all). Median time to first CSBM in CIC and IBS‐C populations were significantly shorter with plecanatide 3 mg versus placebo (p = 0.01 for both). Conclusions and Inferences: Plecanatide was effective in the treatment of severe constipation in adults with CIC or IBS‐C. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) are a mainstay treatment for acid peptic disorders such as gastroesophageal reflux disease (GERD). Although PPIs are considered first-line medications for acid suppression, they have notable limitations such as requiring acid-mediated activation, short half-life and duration of action, and metabolic variability. Fexuprazan is a newly developed potassium-competitive acid blocker (P-CAB), which inhibits acid generation and secretion in a competitive and reversible manner. Fexuprazan, like other P-CABs, has significantly different pharmacodynamic and pharmacokinetic properties than PPIs with potential advantages including rapid, robust, and durable acid suppression, lack of CYP2C19 metabolism, independence from food intake, and no requirement for activation into an active form. Completed clinical trials of fexuprazan have demonstrated comparable efficacy to PPIs for the healing of erosive esophagitis and relief of GERD-related esophageal symptoms without concerning safety signals. Ongoing clinical trials are evaluating fexuprazan for the prevention of NSAID-induced peptic ulcer disease, non-erosive GERD, and acute and chronic gastritis, as well as healing efficacy and maintenance of erosive esophagitis (EE). Fexuprazan is approved in South Korea for the treatment of EE and at the time of this writing is being considered for regulatory approval in several other countries. In this article, we summarize and discuss the pharmacology, efficacy, and safety of fexuprazan. [ABSTRACT FROM AUTHOR]

This study evaluates the onset, magnitude, and consistency of improvement of opioid-induced constipation (OIC) symptoms with naloxegol treatment.Methods: This was a pooled analysis of two Phase 3, double-blind, randomized, placebo-controlled studies (KODIAC-04/05, NCT01309841/NCT01323790) in patients with chronic non-cancer pain and OIC treated with naloxegol 25mg or 12.5mg daily. This analysis assessed improvements in response rates, frequency of spontaneous bowel movement (SBM) and complete SBMs (CSBM), OIC constipation symptoms (straining, stool consistency), time to first post-dose SBM and CSBM, and onset of adverse events over the 12-week period.Subjects: The population of 1337 subjects had a mean age of 52 years and mean duration of opioid use of 3.6 years at baseline. Mean SBM frequency was 1.4/week.Results: Naloxegol 25mg and 12.5mg demonstrated significantly higher response rates vs placebo (PBO) [41.9% (P < 0.001), 37.8% (P = 0.008), 29.4% respectively]. Rapid (within 1 week) and sustained (over 12 weeks) symptom improvement was significantly greater for naloxegol vs PBO (P < 0.05). Both doses showed statistically significant and clinically meaningful improvements in straining, stool consistency, number of SBMs and CSBMs/wk. Significantly shorter times to first post-dose SBM and CSBM were observed with naloxegol vs PBO (SBM HR: 25mg = 1.90, 12.5mg= 1.60; CSBM HR: 25mg = 1.42, 12.5mg = 1.36; P < 0.001 for each regimen). Adverse events occurred more frequently in the naloxegol 25mg group and were most frequently reported during the first week.Conclusion: In patients with chronic non-cancer pain, naloxegol 25mg and 12.5mg demonstrated significantly higher response rates and rapid and sustained improvements in OIC symptoms compared with PBO. [ABSTRACT FROM AUTHOR]

Background: Olorinab is a highly selective, peripherally acting, full agonist of cannabinoid receptor 2. This study assessed the efficacy and safety of olorinab to treat abdominal pain in patients with irritable bowel syndrome with diarrhea (IBS‐D) and constipation (IBS‐C). Methods: CAPTIVATE was a phase 2b, randomized, double‐blind, placebo‐controlled, parallel‐group trial. Eligible participants aged 18–70 years with IBS‐C and IBS‐D diagnosed per Rome IV received olorinab 10 mg, 25 mg, or 50 mg three times daily (TID) or placebo TID for 12 weeks. The primary endpoint was the change in patient‐reported average abdominal pain score (AAPS) from baseline to Week 12. Key Results: A total of 273 participants were randomized to receive olorinab 10 mg (n = 67), olorinab 25 mg (n = 67), olorinab 50 mg (n = 69), or placebo (n = 70). Although a treatment response was observed across all groups, the weekly change in average AAPS from baseline to Week 12 was not significantly different between placebo and any olorinab dose. In a prespecified subgroup analysis of participants with a baseline AAPS ≥6.5, olorinab 50 mg (n = 35) significantly improved AAPS compared with placebo (n = 30) (p = 0.014). Adverse event rates were comparable between olorinab and placebo and there were no reported serious adverse events or deaths. Conclusion and Inferences: Although olorinab was well‐tolerated and improved weekly AAPS, the primary endpoint was not met. However, in participants with moderate‐to‐severe pain at baseline (AAPS ≥6.5), olorinab 50 mg significantly improved weekly AAPS compared with placebo. ClinicalTrials.gov: NCT04043455. [ABSTRACT FROM AUTHOR]

There have been multiple recent updates for recommendations pertaining to colorectal cancer (CRC) screening. Among the most notable is the recommendation from several guideline-issuing bodies to initiate CRC screening examinations at 45 years of age for individuals at average risk for CRC. Current CRC screening methods include stool-based tests and colon visualization examinations. Currently recommended stool-based tests include fecal immunochemical testing, high-sensitivity guaiac-based fecal occult blood testing, and multitarget stool DNA testing. Visualization examinations include colonoscopy, computed tomography colonography, colon capsule endoscopy, and flexible sigmoidoscopy. Although these screening tests have shown encouraging results for CRC detection, there are important differences between these testing modalities for precursor lesion detection and management. In addition, emerging CRC screening methods are being developed and evaluated. However, additional large, multicenter clinical trials in diverse populations are needed to validate the diagnostic accuracy and generalizability of these new tests. This article reviews the recently updated CRC screening recommendations and current and emerging testing options. [ABSTRACT FROM AUTHOR]

Background: This analysis characterized changes in sodium levels in patients receiving the 1 L polyethylene glycol-based preparation NER1006.Methods: Data were pooled from three phase III, randomized clinical trials. A post hoc subanalysis included adults who received a 2-day split-dose (evening/morning) NER1006 regimen, a 1-day split-dose (morning only) regimen, or evening-before regimen and had an increase in sodium concentrations from normal to above the upper limit of normal (143-148 mmol/L) at ≥ 1 of three post-treatment visits. Blood samples were collected at baseline, day of colonoscopy (visit 2), 2 ± 1 days post-colonoscopy (visit 3), and 7 ± 1 days post-colonoscopy (visit 4).Results: A total of 214 of 1028 patients were included. Of the 214 patients, sodium concentration increased from a mean baseline value of 141.8 mmol/L to a mean of 147.1 mmol/L (median increase from baseline of approximately 5 mmol/L). The mean sodium concentration was within normal range at visit 3 (142.3 mmol/L) and visit 4 (142.4 mmol/L), as was the median sodium concentration. Overall, ~ 90% of patients had a normal serum concentration at visits 3 and 4. Based on day of colonoscopy test results, there were four adverse events involving hypernatremia (0.4% of 1028), which were mild and did not require medical intervention; sodium levels returned to normal range by visit 3.Conclusion: NER1006 was associated with small, transient increases in sodium levels that were not considered clinically significant. Trial registration NOCT (ClinicalTrials.gov: NCT02254486 [registered October 2, 2014]), MORA (ClinTrials.gov: NCT02273167 [registered October 23, 2014]; EudraCT number: 2014-002185-78 [registered August 13, 2014]), DAYB (ClinicalTrials.gov: NCT02273141 [registered October 23, 2014]; EudraCT Number: 2014-002186-30 [registered August 12, 2014]). [ABSTRACT FROM AUTHOR]

Background: A randomized, placebo-controlled clinical trial (FDREST) of a novel formulation of caraway oil and L-menthol (COLM-SST) demonstrated symptom relief in patients with functional dyspepsia (FD). Two follow-up studies were conducted to evaluate patient satisfaction, self-regulated dosing, and long-term safety data: FDACT, Functional Dyspepsia Adherence and Compliance Trial, and FDSU36, Functional Dyspepsia Safety Update at 36 months.Methods: A patient reported outcomes (PRO) questionnaire was designed and distributed online to assess real-world satisfaction and dosing frequency of open-label COLM-SST in patients with FD. A separate study analyzing voluntary safety surveillance data evaluated the frequency and severity of reported adverse events (AEs).Results: A total of 600 FD patients were enrolled in the PRO study. Ninety five percent of respondents reported a major or moderate improvement in their FD symptoms and 91.7% indicated a major or moderate improvement in quality of life (QOL) using COLM-SST. Between 1 and 4 capsules were consumed daily by 91.2% of respondents, with 56.2% taking them before meals. Symptom relief was rapid, with 86.4% of respondents indicating relief within 2 h of taking COLM-SST. Few adverse events (AEs) were reported (0.0187%) by patients using COLM-SST. No serious AEs were identified.Conclusion: COLM-SST is safe, well tolerated, and provides rapid relief of FD symptoms. These findings, demonstrated in the FDREST trial, were further supported by a large prospective PRO study evaluating self-regulated dosing frequency, symptom improvement, and QOL. COLM-SST was well-tolerated based on review of AE data at 36 months. [ABSTRACT FROM AUTHOR]

Background: Eluxadoline, a United States Food and Drug Administration (FDA)-approved treatment for irritable bowel syndrome with diarrhea (IBS-D), underwent a change to its US prescribing information on 21 April 2017, contraindicating it in patients without a gallbladder due to increased risk of pancreatitis. This study aimed to elucidate the potential role of eluxadoline's label change on the number of reported spontaneous adverse events (AEs) of pancreatitis. Methods: A pharmacovigilance database (Oracle Argus) was searched for eluxadoline use and spontaneously reported pancreatitis cases from 1 January 2016 to 30 June 2018. Pancreatitis cases were reported as a proportion of the total number of reported AE cases in the safety database. The FDA's adverse event reporting system (AERS) was also interrogated for cases of pancreatitis concomitantly reported with eluxadoline use. Results: In patients who received eluxadoline, 273 reported cases of pancreatitis were recorded (total AEs n = 2191; 12.5%). When known, 28.2% of patients reporting pancreatitis had intact gallbladders (49/174). Eluxadoline was withdrawn in 97.5% of cases, with 87.1% of patients improving or recovered at time of reporting. Importantly, the reporting proportion of pancreatitis cases decreased from 14.4% to 8.9% post label change. Findings were supported by the AERS results, which demonstrated a decrease in reporting proportion from 21.2% to 12.8%. Conclusions: While cautious interpretation is warranted, post-marketing data indicate that the contraindication of eluxadoline in patients without a gallbladder led to reduced reported cases of pancreatitis, with no additional reports of moderately severe or severe cases. Eluxadoline is a safe and well-tolerated treatment option for IBS-D when used according to the label. [ABSTRACT FROM AUTHOR]

Background: NER1006 (Plenvu®, Salix Pharmaceuticals, Bridgewater, NJ) is a 1 L polyethylene glycol bowel preparation indicated for colonoscopy in adults. A US online survey assessed real-world ease of use and treatment satisfaction in individuals who received NER1006.Methods: Adults were recruited from 444 US community gastrointestinal practices and provided a kit number for enrollment into an online survey to be completed within 2 weeks. Survey questions evaluated colonoscopy history and prior bowel preparation(s) prescribed, patient experience during NER1006 administration, and patient satisfaction with the bowel preparation process. A 9-point predefined grading scale was used to evaluate ease of NER1006 preparation and consumption (range, 1 "very difficult" to 9 "very easy"); the perceived importance of volume requirement and clear liquid options (range, 1 "not important at all" to 9 "very important"); and patient satisfaction (range, 1 "not satisfied at all" to 9 "very satisfied").Results: 1630 patients were enrolled, 1606 underwent colonoscopy, and 1598 completed the survey between September 15, 2018 and February 28, 2019. Among 1606 patients who had a colonoscopy, 62.5% were female, and the mean patient age was 54.4 years (range 18-89 years). Most patients (74.7%) did not report a family history of colon cancer, 62.6% had undergone prior colonoscopy, and 64.8% were undergoing colonoscopy for routine colorectal cancer screening. A majority (76.1%) of patients who completed the survey reported that NER1006 was very easy to prepare and take, and 89.9% were very or moderately satisfied with NER1006 overall. Most (97.6%) patients reported consuming all or most of the bowel preparation. Among 1005 patients with previous bowel preparation use, 84.7% indicated that their experience with NER1006 was much better or better (65.3%) or about the same (19.4%) compared with previously used bowel preparations, while only 15.3% rated NER1006 as worse or much worse.Conclusions: In this first real-world, US multicenter survey, patient-reported experience with NER1006 as a bowel preparation for colonoscopy was favorable and adherence was high. The majority of patients were very or moderately satisfied with the overall experience and found it much better/better than previously used bowel preparations.Trial Registration: Not applicable. [ABSTRACT FROM AUTHOR]

Background: Eluxadoline, a United States Food and Drug Administration (FDA)-approved treatment for irritable bowel syndrome with diarrhea (IBS-D), underwent a change to its US prescribing information on 21 April 2017, contraindicating it in patients without a gallbladder due to increased risk of pancreatitis. This study aimed to elucidate the potential role of eluxadoline's label change on the number of reported spontaneous adverse events (AEs) of pancreatitis. Methods: A pharmacovigilance database (Oracle Argus) was searched for eluxadoline use and spontaneously reported pancreatitis cases from 1 January 2016 to 30 June 2018. Pancreatitis cases were reported as a proportion of the total number of reported AE cases in the safety database. The FDA's adverse event reporting system (AERS) was also interrogated for cases of pancreatitis concomitantly reported with eluxadoline use. Results: In patients who received eluxadoline, 273 reported cases of pancreatitis were recorded (total AEs n = 2191; 12.5%). When known, 28.2% of patients reporting pancreatitis had intact gallbladders (49/174). Eluxadoline was withdrawn in 97.5% of cases, with 87.1% of patients improving or recovered at time of reporting. Importantly, the reporting proportion of pancreatitis cases decreased from 14.4% to 8.9% post label change. Findings were supported by the AERS results, which demonstrated a decrease in reporting proportion from 21.2% to 12.8%. Conclusions: While cautious interpretation is warranted, post-marketing data indicate that the contraindication of eluxadoline in patients without a gallbladder led to reduced reported cases of pancreatitis, with no additional reports of moderately severe or severe cases. Eluxadoline is a safe and well-tolerated treatment option for IBS-D when used according to the label. [ABSTRACT FROM AUTHOR]

Source Citation: Ford AC, Wright-Hughes A, Alderson SL, et al; ATLANTIS trialists. Amitriptyline at low-dose and titrated for irritable bowel syndrome as second-line treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023;402:1773-1785. 37858323 Clinical Impact Ratings: GIM/FP/GP: Gastroenterology: [ABSTRACT FROM AUTHOR]

Background: Diarrhea-predominant irritable bowel syndrome (IBS-D) impairs patient quality of life (QOL). Rifaximin is an oral, nonsystemic antibiotic indicated for IBS-D. The objective of this secondary analysis was to evaluate rifaximin retreatment on IBS-related QOL in patients with IBS-D. Methods: Patients received open-label rifaximin 550 mg three times daily for 2 weeks. Clinical responders [simultaneously meeting weekly response criteria for abdominal pain (⩾30% improvement from baseline in mean weekly pain score) and stool consistency (⩾50% decrease from baseline in number of days/week with Bristol Stool Scale (BSS) type 6 or 7 stools) during ⩾2 of first 4 weeks posttreatment] who relapsed during an up to 18-week treatment-free observation phase were randomly assigned to receive two 2-week courses of double-blind rifaximin or placebo, separated by 10 weeks. A validated 34-item IBS-QOL questionnaire examined patient responses in 8 domains. Results: The 2579 patients receiving open-label rifaximin experienced a mean improvement from baseline in IBS-QOL overall score of 54.9%. Responders to open-label rifaximin (n = 1074 of 2438 evaluable; 44.1%) had significantly greater improvement from baseline in IBS-QOL overall and all eight subdomain scores, including dysphoria, food avoidance, interference with activity, body image, and sexual function versus nonresponders at 4 weeks posttreatment (n = 1364; p < 0.001 for all comparisons). A significantly greater percentage of responders to open-label rifaximin achieved the minimally clinically important difference (MCID; ⩾14-point improvement from baseline) in the overall IBS-QOL score versus nonresponders [n = 561 (52.2%) versus n = 287 (21.0%); p < 0.0001]. Among 636 patients with IBS-D relapse, the MCID in the overall IBS-QOL score was achieved by a significantly greater percentage of patients receiving double-blind rifaximin versus placebo (38.6% versus 29.6%, respectively; p = 0.009). Conclusions: Open-label and blinded retreatment with a short course (2 weeks) of rifaximin improved IBS-QOL in patients with IBS-D [ClinicalTrials.gov identifier: NCT01543178]. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by abdominal pain associated with defecation with altered stool frequency or stool form. The global prevalence of IBS ranges from 10% to 15% and total healthcare cost attributable to IBS is significant. Among individuals with IBS, the condition has dramatic effects on health-related quality of life, work and school productivity, and activities of daily living. It may be diagnosed with confidence, based on symptom-based diagnostic criteria, exclusion of alarm features and directed diagnostic testing. Management of IBS typically begins with dietary and lifestyle modifications, progressing to over-the-counter therapies, and then to prescription medications, both approved and nonapproved for IBS. This narrative summarizes the efficacy and safety of three US Food and Drug Administration (FDA)-approved prescription therapies for IBS with diarrhea (IBS-D), with a focus on the most recently marketed agent, eluxadoline, and its role in the treatment IBS-D. [ABSTRACT FROM AUTHOR]

Purpose of Review Opioids are a mainstay in the treatment of chronic non-cancer pain syndromes, but their analgesic benefits come at a cost as opioid-related constipation occurs in 40– 80% of individuals taking chronic opioids. Furthermore, as 10–20% of the population suffers from constipation at baseline, it should be expected that while a proportion of individuals will develop constipation as a direct consequence of opioids (OIC), others will experience it as an exacerbation of their baseline constipation (OEC). Herein, we review the evidencebased data for treatments directed at opioid-related constipation focusing on individuals with non-cancer pain syndromes and provide a template for the development of differentiated treatment algorithms for OIC and OEC. Recent Findings Historical and current treatment protocols recommend traditional laxatives, but these are ineffective in up to 50%, due in part to the heterogeneous pathogenesis of constipation. Therapeutic decisions must be tailored to account for this overlapping pathogenesis. Summary OIC and OEC are distinct entities. As such, additional research and guidelines should address these as different patient populations. [ABSTRACT FROM AUTHOR]

Source Citation: Gearry R, Fukudo S, Barbara G, et al. Consumption of 2 green kiwifruits daily improves constipation and abdominal comfort—results of an international multicenter randomized controlled trial. Am J Gastroenterol. 9 Jan 2023. [Epub ahead of print]. 36537785 Clinical Impact Ratings: GIM/FP/GP: Gastroenterology: [ABSTRACT FROM AUTHOR]

Background: Peppermint oil (PO) has shown promise as an IBS therapy, but previous trials have demonstrated variable efficacy and tolerability results.Aims: To evaluate the efficacy and tolerability of a novel formulation of PO designed for sustained release in the small intestine in patients with IBS-M and IBS-D.Methods: This is a 4-week, randomized, double-blind, placebo-controlled clinical trial of PO or identical placebo 3 times daily in patients fulfilling Rome III criteria for IBS-M or IBS-D. The primary endpoint was the change from baseline in the Total IBS Symptom Score (TISS) after 4 weeks of treatment.Results: Seventy-two patients (mean age 40.7 years, 75 % female, 77.8 % white) were randomized to PO (n = 35) or placebo (n = 37). At 4 weeks, PO was associated with a 40 % reduction in the TISS from baseline (mean change -1.16, SD ± 0.807), superior to the 24.3 % decrease (mean change -0.70, SD ± 0.737) observed with placebo (P = 0.0246). The decrease in the TISS of 19.6 % (mean change -0.55, SD ± 0.613) in the PO group at 24 h was also significantly larger than placebo (-10.3 %, mean change -0.27, SD ± 0.342) (P = 0.0092). At trial completion, patients in the PO group experienced greater improvement in multiple individual gastrointestinal symptoms as well as in severe or unbearable symptoms, compared to placebo. PO was well tolerated with few adverse events.Conclusions: A novel PO formulation designed for sustained release in the small intestine is a safe, effective treatment capable of providing rapid relief of IBS symptoms. [ABSTRACT FROM AUTHOR]

Objective It is unclear whether Barrett's oesophagus (BO) length changes over time or whether the full length of the segment is established at the onset of disease recognition. The objectives of this study were to evaluate the association of age and BO length and to evaluate the changes in BO length over time. Design This is a prospective, multicentre cohort study involving patients with BO from five centres. Patients were divided into groups based on the decade of initial diagnosis of BO. The mean BO length and the mean change in BO length were calculated for each age decade. The mean change in BO length was also calculated between the index endoscopy and the last surveillance endoscopy. Results 3635 patients with BO were included in the study: 87.8% men, 92.8% Caucasians, mean age 60.9 years and mean BO length 3.5 cm. The mean change in BO length was 0.9 cm. The mean BO length did not significantly change for each age category: <30 years (4.6 cm), 30-39.9 years (3.2 cm), 40-49.9 years (3.1 cm), 50-59.9 years (3.1 cm), 60-69.9 years (3.6 cm), 70-79.7 (4.0 cm) and >80 years (4.5 cm), p=0.47. On subgroup analysis of patients with non-dysplastic BO who had at least 1 year of endoscopic follow up, there was a significant decrease in mean change in BO length across age categories ranging from +1.7 to -0.8 cm, p=0.03. Conclusions There was no significant difference in BO length by age category in decades. In addition, the change in BO length from index to follow-up endoscopy was similar among patients >30 years. These findings suggest that a patient's BO segment length attains its full extent by the time of the initial endoscopic examination. [ABSTRACT FROM AUTHOR]

Chronic constipation is a common health condition representing a substantial proportion of primary care visits and referrals to specialist providers. Chronic constipation can have a significant negative effect on health-related quality of life and has been associated with psychological distress in severely affected patients. It has the potential to cause patients to curtail work, school, and social activities. While different pathophysiological mechanisms have been implicated in the development of chronic constipation, in some instances, the causes of chronic constipation are not easily determined. Expenditures for the evaluation and management of chronic constipation represent a significant burden on patients and payers, and it is important for clinicians to have a clear understanding of the different pathophysiological mechanisms associated with constipation, understand the different testing modalities and treatments that are available including their appropriateness and limitations, and tailor that knowledge to the management of individual patients. [ABSTRACT FROM AUTHOR]

Background and study aim: Data are limited on the natural history of patients with Barrett's esophagus with a diagnosis of "indefinite for dysplasia" (IND). The aims of this study were to: (i) determine rates of progression to high grade dysplasia (HGD) or esophageal adenocarcinoma, and compare these with rates for low grade dysplasia (LGD); and (ii) determine the proportion of patients whose histological IND diagnosis changed on follow-up endoscopy. Patients and methods: Demographic, endoscopic, and histologic information of patients with diagnoses of IND and LGD and at least 12 months of follow-up were extracted from the database of a multicenter Barrett's esophagus study. Rates and times for progression to HGD and esophageal adenocarcinoma and regression to nondysplastic epithelium were calculated. Proportions of diagnoses upgraded to HGD/esophageal adenocarcinoma or downgraded to nondysplastic epithelium at first follow-up endoscopy were evaluated. Results: Amongst 2264 patients, 83 with a diagnosis of IND (mean age 60 years, 95% men, 95% white; mean follow-up 5.6 years) and 79 with diagnosis of LGD were identified. In the IND group, annual incidences of esophageal adenocarcinoma and HGD were 0.21% and 0.64 %, respectively, representing a combined incidence of 0.8 %. Mean time to progression was 4.72 years. Within the IND group 55% patients showed regression to nondysplastic epithelium at first follow-up endoscopy and the overall regression rate was 80%. Corresponding rates in LGD patients were similar. Conclusions: Lesions diagnosed as IND and LGD show similar biological behavior and can be treated as a single category with respect to surveillance and follow-up. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) patients, specifically those with Crohn’s disease and ulcerative colitis, are at an increased risk of developing adverse events either related to disease course or therapeutic interventions. These risks can be mitigated by ensuring the patient is current on all aspects of their general health maintenance. This article is intended to serve as a guide regarding the health maintenance issues of the patient with IBD with recommendations for screening and surveillance intervals. [ABSTRACT FROM AUTHOR]

Medical imaging involving the use of ionizing radiation has brought enormous benefits to society and patients. In the past several decades, exposure to medical radiation has increased markedly, driven primarily by the use of computed tomography. Ionizing radiation has been linked to carcinogenesis. Whether low-dose medical radiation exposure will result in the development of malignancy is uncertain. This paper reviews the current evidence for such risk, and aims to inform the gastroenterologist of dosages of radiation associated with commonly ordered procedures and diagnostic tests in clinical practice. The use of medical radiation must always be justified and must enable patients to be exposed at the lowest reasonable dose. Recommendations provided herein for minimizing radiation exposure are based on currently available evidence and Working Party expert consensus. [ABSTRACT FROM AUTHOR]

The article discusses a study that evaluates the potential role of probiotics and antimicrobials for management of functional bowel disorders with a focus on irritable bowel syndrome. Topics discussed include the PubMed database search in July 2013 for English-language articles, a table outlining intrinsic and extrinsic factors that can influence the gut microbiota, and a list of commonly used probiotic formulations.

Background: Barrett's esophagus (BE) is a metaplastic precursor lesion of esophageal adenocarcinoma (EA), the most rapidly increasing cancer in western societies. While the prevalence of BE is increasing, the vast majority of EA occurs in patients with undiagnosed BE. Thus, we sought to identify genes that are altered in BE compared to the normal mucosa of the esophagus, and which may be potential biomarkers for the development or diagnosis of BE. Design: We performed gene expression analysis using HG-U133A Affymetrix chips on fresh frozen tissue samples of Barrett's metaplasia and matched normal mucosa from squamous esophagus (NE) and gastric cardia (NC) in 40 BE patients. Results: Using a cut off of 2-fold and P<1.12E-06 (0.05 with Bonferroni correction), we identified 1324 differentially-expressed genes comparing BE vs NE and 649 differentially-expressed genes comparing BE vs NC. Except for individual genes such as the SOXs and PROM1 that were dysregulated only in BE vs NE, we found a subset of genes (n = 205) whose expression was significantly altered in both BE vs NE and BE vs NC. These genes were overrepresented in different pathways, including TGF-β and Notch. Conclusion: Our findings provide additional data on the global transcriptome in BE tissues compared to matched NE and NC tissues which should promote further understanding of the functions and regulatory mechanisms of genes involved in BE development, as well as insight into novel genes that may be useful as potential biomarkers for the diagnosis of BE in the future. [ABSTRACT FROM AUTHOR]

Background: Irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) symptoms often overlap. In some IBS cases there are subtle inflammatory changes similar to the immune-mediated pathophysiology of IBD, and the risk of both increases after infectious gastroenteritis (IGE). Methods: To evaluate the effect of IBS and IGE on IBD risk utilizing US Department of Defense medical encounter data, active duty personnel with IBS were matched to subjects without IBS. Medical encounter history was analyzed to assess for incident IBD. IGE was identified from documented medical encounters and by self-report. Relative risks were calculated using Poisson regression models. Results: We identified 9,341 incident IBS cases and 18,678 matched non-IBS subjects and found an 8.6-fold higher incidence (p<0.0001) of IBD among those with IBS (238.1 per 100,000 person-years) compared to our referent population (27.8 per 100,000 person-years). In a subset (n = 2,205) of well-defined IBS cases, IBD risk was 15 times that of subjects without IBS. The median time between IBS and IBD diagnoses was 2.1 years. IGE also increased IBD risk approximately 2-fold (p<0.05) after controlling for IBS. Conclusions: These data reflect a complex interaction between illness presentation and diagnosis of IBS and IBD and suggest intercurrent IGE may increase IBD risk in IBS patients. Additional studies are needed to determine whether IBS lies on the causal pathway for IBD or whether the two are on a pathophysiological spectrum of the same clinical illness. These data suggest consideration of risk reduction interventions for IGE among IBS patients at high disease risk. [ABSTRACT FROM AUTHOR]

Introduction: Military personnel are frequently deployed to regions of the world with high travelers' diarrhea (TD) rates. Pathogens associated with TD have been linked to several post-infectious sequelae, including functional gastrointestinal disorders (FGD), such as irritable bowel syndrome (IBS) and functional dyspepsia. Furthermore, stress associated with deployment may potentiate the increased FGD risk.Aim: We sought to assess whether self-reported diarrhea, vomiting, and stressors during deployment were associated with increased FGD risk.Methods: Using active duty military medical encounter data from the Defense Medical Surveillance System (DMSS), we conducted a matched case-control study to assess the odds of FGD (IBS, functional constipation, functional diarrhea, dyspepsia) following self-reported diarrhea or vomiting during deployment. Only first-time deployers with detailed self-reporting of deployment-related exposures from 2008 and 2009 were included. Univariate and multivariate analyses were performed.Results: A total of 129 cases of FGD were identified, with the following distribution: constipation (n = 67), dyspepsia (n = 15), IBS (n = 22), and overlapping disorders (n = 25). Diarrhea and/or vomiting during deployment were significantly associated with the development of FGD. Other demographic factors were also associated with variable risk. We found no consistent effect of war-related stressors or non-combat-related correlates of stress.Conclusions: Deployment-related TD is common in deployed military personnel and is associated with an increased risk of several FGD. When considering effective countermeasures and mitigation strategies, both the acute effects and chronic sequelae of enteric infections should be considered. Increased emphasis on existing and novel primary prevention strategies are needed, as well as outcome studies among those developing these conditions. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Functional gastrointestinal disorders (FGDs) are recognized sequelae of infectious gastroenteritis (IGE). Within the active duty military population, a group with known high IGE rates, the population-based incidence, risk factors, and attributable burden of care referable to FGD after IGE are poorly defined.METHODS:Using electronic medical encounter data (1999-2007) on active duty US military, a matched, case-control study describing the epidemiology and risk determinants of FGD (irritable bowel syndrome (IBS), functional constipation (FC), functional diarrhea (FD), dyspepsia (D)) was conducted. Incidence rates and duration of FGD-related medical care were estimated, and conditional logistic regression was utilized to evaluate FGD risk after IGE.RESULTS:A total of 31,866 cases of FGD identified were distributed as follows: FC 55% (n=17,538), D 21.2% (n=6,750), FD 2.1% (n=674), IBS 28.5% (n=9,091). Previous IGE episodes were distributed as follows: specific bacterial pathogen (n=65, 1.2%), bacterial, with no pathogen specified (n=2155, 38.9%), protozoal (n=38, 0.7%), viral (n=3431, 61.9%). A significant association between IGE and all FGD (odds ratio (OR) 2.64; P<0.001) was seen, with highest risk for FD (OR 6.28, P<0.001) and IBS (OR 3.72, P<0.001), and moderate risk for FC (2.15, P<0.001) and D (OR 2.39, P<0.001). Risk generally increased with temporal proximity to, and bacterial etiology of, exposure. Duration of FGD-related care was prolonged with 22.7% having FGD-associated medical encounters 5 years after diagnosis.CONCLUSIONS:FGD are common in this population at high risk for IGE. When considering effective countermeasures and mitigation strategies, attention directed toward prevention as well as the acute and chronic sequelae of these infections is needed. [ABSTRACT FROM AUTHOR]

The article discusses the growing debate on the merits and limitations of computed tomographic (CT) colonography for colorectal cancer (CRC). It says that early studies of CT colonography showed excellent per-polyp sensitivity for larger lesions compared with colonoscopy. It concludes that CT colonography is an alternative to CRC screening and the ongoing study and provision of this test have great potential to improve public health. It also recommends gastroenterologists using the test.

OBJECTIVES:There are limited data on the yield of colonoscopy in patients with irritable bowel syndrome (IBS). This study compared the prevalence of structural colonic lesions in patients with suspected non-constipation-predominant IBS and healthy volunteers. We also determined the yield of rectosigmoid biopsies in patients with suspected IBS.METHODS:This was a prospective, case–control study conducted at three US sites. Patients with suspected non-constipation-predominant IBS (Rome II) underwent colonoscopy with rectosigmoid biopsies. Healthy persons undergoing colonoscopy for colorectal cancer screening or polyp surveillance comprised the control group. Abnormalities identified at colonoscopy were compared between suspected IBS and control groups.RESULTS:In all, 466 suspected IBS patients and 451 controls were enrolled. Suspected IBS patients were significantly younger (P<0.0001) and more frequently female (P<0.0001) than controls. The most common lesions in suspected IBS patients were hemorrhoids (18.2%), polyps (14.6%), and diverticulosis (8.8%). Suspected IBS patients had a lower prevalence of adenomas (7.7% vs. 26.1%, P<0.0001) and diverticulosis (8.8% vs. 21.3%, P<0.0001) and higher prevalence of mucosal erythema or ulceration (4.9% vs. 1.8%, P<0.01) compared with controls. Logistic regression found the between-group differences in adenoma prevalence to be robust after correction for demographic factors. The overall prevalence of microscopic colitis in suspected IBS patients was 1.5% (7/466) and 2.3% (4/171) in those ≥45 years of age.CONCLUSIONS:The prevalence of structural abnormalities of the colon is no higher in suspected non-constipation IBS patients than in healthy controls. Microscopic colitis can be identified in a small proportion of persons with IBS symptoms. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Computed tomography colonography (CTC) is an emerging colon cancer screening modality that has the potential to increase adherence to current screening recommendations. Traditionally, the interpretation of CTC has been limited to radiologists. As the technology of CTC has developed, three-dimensional endoluminal fly-through images have largely replaced two-dimensional CT images as the primary reading modality. Such a display is a realistic corollary to the endoscopic view obtained during colonoscopy. Our study sought to determine whether gastroenterologists could interpret the colonic display of CTC with an accuracy similar to that of trained radiologists.METHODS:Three board-certified gastroenterologists and four gastroenterology fellows in various stages of training interpreted a mean of 45 CTCs (range: 30–50) in which colonoscopy had also been performed. Before reading any cases, each reader underwent CTC interpretation training with an experienced CTC radiologist. After interpreting each CTC, the gastroenterologist had access to both the original radiology interpretation of the CTC and the corresponding colonoscopy results. Outcomes included accuracy of the gastroenterologists' interpretation, time required for CTC interpretation, evidence of learning, and the level of diagnostic agreement between gastroenterologists and radiologists.RESULTS:Gastroenterologist readers identified polyps ≥6 mm on CTC with a mean sensitivity and specificity of 83.5% (67–100%) and 78.8% (69–100%), respectively. Corresponding values for polyps ≥8 mm were 83.8% (68–100%) and 74% (30–93%), respectively, and those for polyps ≥10 mm were 87.8% (67–100%) and 85.2% (60–94%), respectively. Overall, 83% (5 of 6) of gastroenterologists achieved κ scores ≥0.60, suggesting good agreement with radiologists; 66% achieved κ≥0.75. There was a direct relationship between diagnostic accuracy and level of gastroenterology training, with third-year fellows being nearly as accurate as the attendings. The average gastroenterologist CTC reading time was 18.4 min (range: 11.2–25.6).CONCLUSIONS:The gastroenterologists in this study were able to read CTCs with an accuracy that approaches that of radiologists. The level of training affected the accuracy of CTC interpretation by the gastroenterologist. Average gastroenterologist CTC interpretation times in this study were similar to recommended colonoscopy times. Further studies are warranted to determine whether gastroenterologists are able to interpret CTCs independently in clinical practice. [ABSTRACT FROM AUTHOR]

The practice of colonic cleansing to promote general health and well-being continues to generate interest among the lay population. These practices are widely touted as adjuncts to improve vitality and as therapeutic modalities to minimize the symptoms, or prevent the actual development, of a variety of chronic disease states. The data supporting colonic cleansing and body “detoxification” have not been studied well in a systematic manner. This report describes a systematic review of the published literature of both the traditional and complementary and alternative medicine arenas that was performed in an attempt to qualify and quantify the value of colonic cleansing. The investigators concluded that there are no methodologically rigorous controlled trials of colonic cleansing to support the practice for general health promotion. Conversely, there are multiple case reports and case series that describe the adverse effects of colonic cleansing. The practice of colonic cleansing to improve or promote general health is not supported in the published literature and cannot be recommended at this time. [ABSTRACT FROM AUTHOR]

OBJECTIVES:No previous study has concurrently assessed the associations between meat intake, meat-cooking methods and doneness levels, meat mutagens (heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons), heme iron, and nitrite from meat and colorectal adenoma in asymptomatic women undergoing colonoscopy.METHODS:Of the 807 eligible women in a cross-sectional multicenter colonoscopy screening study, 158 prevalent colorectal adenoma cases and 649 controls satisfactorily completed the validated food frequency and meat questionnaires. Using an established meat mutagen database and new heme iron and nitrite databases, we comprehensively investigated the components of meat that may be involved in carcinogenesis. Using logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) within quartiles of meat-related variables.RESULTS:Red meat was associated positively with colorectal adenoma (OR fourth vs. first quartile=2.02; 95% CI=1.06–3.83; P trend=0.38). Intake of pan-fried meat (OR=1.72; 95% CI=0.96–3.07; P trend=0.01) and the HCA: 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) (OR=1.90; 95% CI=1.05–3.42; P trend=0.07) were also associated with an increased risk of colorectal adenoma. The new databases yielded lower estimates of heme iron and nitrite than previous assessment methods, although the two methods were highly correlated for both exposures. Although not statistically significant, there were positive associations between iron and heme iron from meat and colorectal adenoma.CONCLUSIONS:In asymptomatic women undergoing colonoscopy, colorectal adenomas were associated with high intake of red meat, pan-fried meat, and the HCA MeIQx. Other meat-related exposures require further investigation.Am J Gastroenterol 2009; 104:1231–1240; doi:10.1038/ajg.2009.102; published online 14 April 2009 [ABSTRACT FROM AUTHOR]