Baseline Features and Reasons for Nonparticipation in the Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) Study, a Colorectal Cancer Screening Trial.

Importance: The Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) randomized clinical trial sought to recruit 50 000 adults into a study comparing colorectal cancer (CRC) mortality outcomes after randomization to either an annual fecal immunochemical test (FIT) or colonoscopy. Objective: To (1) describe study participant characteristics and (2) examine who declined participation because of a preference for colonoscopy or stool testing (ie, fecal occult blood test [FOBT]/FIT) and assess that preference's association with geographic and temporal factors. Design, Setting, and Participants: This cross-sectional study within CONFIRM, which completed enrollment through 46 Department of Veterans Affairs medical centers between May 22, 2012, and December 1, 2017, with follow-up planned through 2028, comprised veterans aged 50 to 75 years with an average CRC risk and due for screening. Data were analyzed between March 7 and December 5, 2022. Exposure: Case report forms were used to capture enrolled participant data and reasons for declining participation among otherwise eligible individuals. Main Outcomes and Measures: Descriptive statistics were used to characterize the cohort overall and by intervention. Among individuals declining participation, logistic regression was used to compare preference for FOBT/FIT or colonoscopy by recruitment region and year. Results: A total of 50 126 participants were recruited (mean [SD] age, 59.1 [6.9] years; 46 618 [93.0%] male and 3508 [7.0%] female). The cohort was racially and ethnically diverse, with 748 (1.5%) identifying as Asian, 12 021 (24.0%) as Black, 415 (0.8%) as Native American or Alaska Native, 34 629 (69.1%) as White, and 1877 (3.7%) as other race, including multiracial; and 5734 (11.4%) as having Hispanic ethnicity. Of the 11 109 eligible individuals who declined participation (18.0%), 4824 (43.4%) declined due to a stated preference for a specific screening test, with FOBT/FIT being the most preferred method (2820 [58.5%]) vs colonoscopy (1958 [40.6%]; P < .001) or other screening tests (46 [1.0%] P < .001). Preference for FOBT/FIT was strongest in the West (963 of 1472 [65.4%]) and modest elsewhere, ranging from 199 of 371 (53.6%) in the Northeast to 884 of 1543 (57.3%) in the Midwest (P = .001). Adjusting for region, the preference for FOBT/FIT increased by 19% per recruitment year (odds ratio, 1.19; 95% CI, 1.14-1.25). Conclusions and Relevance: In this cross-sectional analysis of veterans choosing nonenrollment in the CONFIRM study, those who declined participation more often preferred FOBT or FIT over colonoscopy. This preference increased over time and was strongest in the western US and may provide insight into trends in CRC screening preferences.

An Expert Consensus to Standardize Assessment of Bowel Cleansing for Clinical Trials of Bowel Preparations for Crohn's Disease.

BACKGROUND: Despite regular need for colonoscopy in patients with Crohn's disease (CD), the efficacy and tolerability of bowel preparation (BP) agents is rarely assessed in this population. Assessing BP quality with existing scales may be challenging in CD due to presence of inflammation, bowel resection, and strictures. AIMS: To provide recommendations for assessing BP quality in clinical trials for CD using a modified Research and Development/University of California, Los Angeles appropriateness process. METHODS: Based on systematic reviews and a literature search, 110 statements relating to BP quality assessment in CD were developed. A panel of 15 gastroenterologists rated the statements as appropriate, uncertain, or inappropriate using a 9-point Likert scale. RESULTS: Panelists considered it appropriate that central readers, either alone or with local assessment, score BP quality in clinical trials. Central readers should be trained on scoring BP quality and local endoscopists on performing high-quality video recording. Both endoscope insertion and withdrawal phases should be reviewed to score BP quality in each colonic segment and segments should align with endoscopic disease activity indices. The Harefield Cleansing Scale and the Boston Bowel Preparation Scale were considered appropriate. The final score should be calculated as the average of all visualized segments. Both total and worst segment scores should also be assessed. CONCLUSIONS: We developed a framework for assessing BP quality in patients with CD based on expert feedback. This framework could support the development or refinement of BP quality scales and the integration of BP quality assessment in future CD studies.

Polyethylene Glycol 3350 in the Treatment of Chronic Idiopathic Constipation: Post hoc Analysis Using FDA Endpoints.

Methods: This multicenter, double-blind, placebo-controlled, parallel-group trial included adults with chronic idiopathic constipation randomized to polyethylene glycol 3350 17 g (n = 204) or placebo (n = 100) once daily for 24 weeks. Post hoc analyses were performed using the US Food and Drug Administration endpoint (≥3 complete spontaneous bowel movements/week and an increase of ≥1 complete spontaneous bowel movement/week from baseline for ≥9/12 weeks, including 3 of the last 4 weeks) along with additional efficacy and safety outcomes. Results: The proportion of patients meeting the new endpoint was significantly higher with polyethylene glycol 3350 vs placebo (42% vs 13%; P < 0.0001). Reductions in the mean number of hard/lumpy stools/week (-2.1 vs -0.9; P = 0.0014) and the weekly mean five-point cramping rating (-0.3 vs -0.1; P = 0.0272) also significantly favored polyethylene glycol 3350. The proportion of subjects with gastrointestinal adverse events decreased markedly after the first week of treatment in the polyethylene glycol 3350 group. Conclusion: Using the current US Food and Drug Administration-recommended responder definition and other secondary outcomes, once-daily polyethylene glycol 3350 demonstrated substantial and sustained efficacy and safety over 24 weeks in patients with chronic idiopathic constipation. Trial Registration. The original trial was registered with https://clinicaltrials.gov Trial: NCT00153153.

A Randomized Pilot Study to Compare the Effectiveness of a Low FODMAP Diet vs Psyllium in Patients With Fecal Incontinence and Loose Stools.

INTRODUCTION: The aim of the study was to compare the effectiveness of a low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol diet (LFD) vs psyllium on the frequency and severity of fecal incontinence (FI) episodes in patients with loose stools. METHODS: This was a single-center, randomized pilot trial of adult patients with FI (Rome III) with at least 1 weekly FI episode associated with loose stool. Eligible patients were randomized to 4 weeks of either a dietitian-led LFD or 6 g/d psyllium treatment. RESULTS: Forty-three subjects were randomized from October 2014 to May 2019. Thirty-seven patients completed the study (19 LFD and 18 psyllium). There was no statistically significant difference in the proportion of treatment responders (>50% reduction in FI episodes compared with baseline) for treatment weeks 1-4 (LFD 38.9%, psyllium 50%, P = .33). Compared with baseline, mean fecal incontinence severity index score significantly improved with LFD (39.4 vs 32.6, P = .02) but not with psyllium (35.4 vs 32.1, P = .29). Compared with baseline values, the LFD group reported improvements in fecal incontinence quality of life coping/behavior, depression/self-perception, and embarrassment subscales. The psyllium group reported improvement in incontinence quality of life coping/behavior. DISCUSSION: In this pilot study, there was no difference in the proportion of patients who reported a 50% reduction of FI episodes with the LFD or psyllium. Subjects in the psyllium group reported a greater reduction in overall FI episodes, whereas the LFD group reported consistent improvements in FI severity and quality of life. Further work to understand these apparently discrepant results are warranted but the LFD and psyllium seem to provide viable treatment options for patients with FI and loose stools.

Regression and Random Forest Machine Learning Have Limited Performance in Predicting Bowel Preparation in Veteran Population.

BACKGROUND: Inadequate bowel preparation undermines the quality of colonoscopy, but patients likely to be affected are difficult to identify beforehand. AIMS: This study aimed to develop, validate, and compare prediction models for bowel preparation inadequacy using conventional logistic regression (LR) and random forest machine learning (RFML). METHODS: We created a retrospective cohort of patients who underwent outpatient colonoscopy at a single VA medical center between January 2012 and October 2015. Candidate predictor variables were chosen after a literature review. We extracted all available predictor variables from the electronic medical record, and bowel preparation from the endoscopy database. The data were split into 70% training and 30% validation sets. Multivariable LR and RFML were used to predict preparation inadequacy as a dichotomous outcome. RESULTS: The cohort included 6,885 Veterans, of whom 964 (14%) had inadequate preparation. Using LR, the area under the receiver operating characteristic curve (AUC) for the validation cohort was 0.66 (95% CI 0.62, 0.69) and the Brier score, in which a lower score indicates better performance, was 0.11. Using RFML, the AUC for the validation cohort was 0.61 (95% CI 0.58, 0.65) and the Brier score was 0.12. CONCLUSIONS: LR and RFML had similar performance in predicting bowel preparation, which was modest and likely insufficient for use in practice. Future research is needed to identify additional predictor variables and to test other machine learning algorithms. At present, endoscopy units should focus on universal strategies to enhance preparation adequacy.

Evaluation of Plecanatide for the Treatment of Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation in Patients 65 Years or Older.

PURPOSE: Chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) are common functional gastrointestinal disorders. The prevalence of constipation-related issues tends to increase with age. This analysis pooled data from Phase III trials in CIC and IBS-C to assess the safety and efficacy of plecanatide in patients aged ≥65 years. METHODS: Patients randomized to receive plecanatide (3 or 6 mg) or placebo from two CIC and two IBS-C trials were pooled. Efficacy end points common to all trials included changes in stool consistency (Bristol Stool Form Scale), changes in weekly frequency of complete spontaneous bowel movements (CSBMs) and spontaneous bowel movements (SBMs), and time to first CSBM and SBM. Efficacy and safety profile results are reported per age group (≥65 and <65 years of age). FINDINGS: The pooled intention-to-treat population comprised 451 patients aged ≥65 years (mean age, 70 years) and 4364 patients aged <65 years (mean age, 41.9 years), of whom 287 and 2914, respectively, were randomized to receive plecanatide. Compared with placebo, plecanatide produced statistically significant improvements in stool consistency from baseline at week 12 (both age groups), CSBM and SBM frequency from baseline at week 12 (plecanatide 3 mg group aged ≥65 years and both plecanatide groups aged <65 years), and time from start of therapy to first CSBM (both age groups) and SBM (plecanatide 6 mg group aged ≥65 years and both plecanatide groups aged <65 years). No new safety issues were observed. IMPLICATIONS: Plecanatide is a well-tolerated and effective treatment option for patients aged ≥65 years with CIC or IBS-C. CLINICALTRIALS. GOV IDENTIFIERS: NCT01982240, NCT02122471, NCT02387359, and NCT02493452.

Comparison of Serum Vitamin D Levels in Relation to Bowel and Bladder Symptoms in Women with Vulvar Diseases.

Objectives: We sought to investigate associations between vitamin D levels and bowel and bladder disorders in women with vulvar diseases. Methods: This is a planned sub-analysis of a cross-sectional study comparing the prevalence of bowel and bladder symptoms in women with biopsy-proven vulvar lichen sclerosus (LS) to a control group of women with non-lichenoid vulvar diseases. All subjects were recruited from a tertiary referral vulvar care clinic in a university-based practice. Serum vitamin D levels were measured and subjects self-completed questionnaires during study recruitment. Pelvic floor disorders were determined from the following questionnaires: Rome III Functional Bowel Disorders Questionnaire, the Bristol stool scale, the Medical, Social and Epidemiologic Aspects of Aging Questionnaire, and the Overactive Bladder-8 Question Version. Results: 181 women with vulvar diseases were included: 88 with LS and 93 with non-LS vulvar diseases. The mean age was 52.5 ± 15.3 years, and 94.5% were Caucasian. Vitamin D levels (26.8 ± 13.1 vs 29.5 ± 19.0 ng/mL), prevalence of low vitamin D levels (51.1% vs 45.2%), and vitamin D supplementation (42.0% vs 47.8%) were similar in women with and without LS (p ≥ 0.27). These factors did not differ between women with and without overactive bladder (OAB) (vitamin D levels 30.1 ± 17.8 vs 26.3 ± 14.8 ng/mL), urinary incontinence (27.9 ± 15.2 vs 26.4 ± 11.0 ng/mL), constipation (26.7 ± 14.8 vs 28.5 ± 16.8 ng/mL), or irritable bowel syndrome (IBS) (30.8 ± 22.1 vs 27.6 ± 13.4 ng/mL). Conclusions: In this cohort of women with vulvar diseases, vitamin D levels and supplementation were not significantly different amongst women with vulvar lichen sclerosus or other non-lichenoid vulvar diseases. Furthermore, vitamin D levels are not serum biomarkers for OAB, urinary incontinence, constipation, or IBS.

Prevalence and Severity of Fecal Incontinence in Veterans.

BACKGROUND/AIMS: Fecal incontinence (FI) is a common complaint that increases in prevalence with age. Our aim was to determine the prevalence of FI and assess its severity by self-report in a male-predominant Veteran outpatient clinic setting. METHODS: An anonymous 28 item questionnaire was administered to a convenience sample of veterans awaiting appointments. FI was defined as a loss of liquid or solid stool at least monthly. Multivariable logistic and linear models were used to identify predictors of FI prevalence and severity. RESULTS: One hundred thirty-three gastroenterology (GI) participants and 126 primary care (PC) participants completed the survey. Ninety-four of 259 participants (36.3%, 95% confidence interval [CI]: 30.4-42.5) reported an episode of FI (41.4% GI participants vs 31.0% PC participants; P = 0.078) with 33.6% having FI within the last 30 days (36.8% GI participants vs 30.2% PC participants; P = 0.122). Participants with more bowel movements per week (P = 0.005) and per day (P < 0.001) and with a higher Bristol Stool Scale form (P = 0.010) were more likely to have FI. Of participants with FI, mean Fecal Incontinence Severity Index score was 23.0 ± 9.5 with a significantly higher symptom score in GI participants compared to PC participants (25.2 ± 10.0 vs 20.1 ± 8.2; P = 0.011). Few participants had ever been asked by (35.0%) or evaluated by (18.0%) a doctor for FI symptoms. CONCLUSION: FI is a common complaint and under-recognized problem in the male-dominant Veteran population. Despite its prevalence, relatively few participants were asked about FI, with even less being treated. Due to the possible effects and implications on quality of life, more should be done to recognize this condition and arrange treatment.

A Low FODMAP Diet May Reduce Symptoms in Patients With Fecal Incontinence.

INTRODUCTION: Fecal incontinence (FI) is a common complaint and is often associated with diarrhea and urgency. Foods high in fermentable oligo-, di-, and mono-saccharides and polyols (FODMAP) cause symptoms of diarrhea and urgency. Therefore, this study assesses the impact of a low FODMAP diet on the occurrence of FI due to loose stool. METHODS: This study is a retrospective chart review of patients with FI seen in the Michigan Bowel Control Program clinic between August 2012 and December 2017. Patients who had FI with loose stool without red flag signs and who were recommended a low FODMAP diet and underwent formal dietary instruction with a Michigan Medicine dietician were included. RESULTS: Sixty-five patients with FI who underwent formal dietary teaching were included in this study. Eighty-eight percent of the patients were white, and 87% were women with a mean age of 62 years (±14 years). Additionally, the chart review showed that 35% of the patients had FI daily, 21.5% had FI weekly, and 5% had FI monthly. About 64.6% of the patients (42) had reported a reduction in their FI symptoms with the low FODMAP diet. There was no demographic or clinical characteristic that predicted the response to a low FODMAP diet. DISCUSSION: In this case series, dietary manipulation with a low FODMAP diet was a useful tool to treat patients who suffer from FI due to loose stool. Further confirmatory, prospective randomized controlled trials are required to see the true efficacy of a low FODMAP diet in patients who suffer with FI.

Hydrogen Breath Testing Predicts Bowel Preparation Quality Prior to Colonoscopy: A Systematic Review.

BACKGROUND: This systematic review aims to assess the accuracy of hydrogen breath testing as a predictor of bowel preparation. METHODS: Studies were identified from MEDLINE, Embase, Web of Science, Cochrane Library and clinicaltrials.gov. Two investigators evaluated abstracts for inclusion criteria - report of correlation between hydrogen breath levels and bowel preparation quality, prospective design and non-emergent colonoscopy in adults. Included studies underwent duplicate data extraction using a standardized approach. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool assessed quality of the studies. RESULTS: One hundred fifty-nine publications were identified, and six unique studies met inclusion criteria. The number of patients analyzed ranged from 61 to 127. Three studies were performed in the USA, one in Japan and two in Italy. Three studies used a prebiotic in addition to a purgative, with the intention of enhancing the discriminating ability of hydrogen breath levels. Three studies assessed baseline hydrogen levels. In five of the six studies, hydrogen breath levels were predictive of inadequate bowel preparation. Suggested absolute hydrogen levels to distinguish adequate from inadequate bowel preparation ranged from 3 to 10 parts per million. Depending on the cutoff value, sensitivity ranged from 71% to 100% and specificity from 87% to 100%. There was significant heterogeneity among studies in breath testing protocol and breath analyzer used. Full-text studies had low risk of bias in most assessed domains. CONCLUSION: Hydrogen breath levels predict bowel preparation adequacy but existing studies have significant limitations. Further studies should use standardized methods and consider the real-world practicality of self-administered home breath testing.

Adherence to CRC Screening and Surveillance Guidelines when Using Split-Dose Bowel Preparation.

GOAL: To prospectively assess physician recommendations for repeat colonoscopy in an average-risk screening cohort. BACKGROUND: Endoscopists' adherence to colorectal cancer screening and surveillance guidelines for repeat colonoscopy have not been well characterized. Furthermore, little is known about patient and colonoscopy factors that are associated with endoscopists' nonadherence to guideline recommendation. STUDY: This is a prospective cohort of average-risk patients undergoing colonoscopy for colorectal cancer screening between August 2011 and January 2013. The primary outcome was assessment of physician recommendations for repeat colonoscopy. RESULTS: 462 participants were prospectively enrolled. 13.6% (62) had guideline-inconsistent recommendations. 89% of the guideline-inconsistent recommendations were for an earlier interval. Endoscopists' reports cited suboptimal bowel preparation as the most common reason for earlier repeat colonoscopy. On multivariable analysis, patient split-dose preparation noncompliance was significantly associated with guideline-inconsistent recommendation (OR = 2.7) even after adjusting for other patient or bowel preparation-related characteristics. Additionally, increased odds of guideline-inconsistent recommendation were associated with older age (>70 years old), higher BMI, having 3 or more polyps, having had at least two previous colonoscopies, suboptimal bowel preparation, and having taken at least 12 hours till clear bowel movement. CONCLUSIONS: Gastroenterologists are adherent to CRC screening and surveillance guidelines. Suboptimal bowel preparation is the most frequently cited factor in endoscopy reports leading to deviation from guidelines. Continued emphasis on optimization of bowel preparation, particularly patient compliance to split-dose regimen, is needed.

Prevalence of and Factors Associated With Fecal Incontinence: Results From a Population-Based Survey.

BACKGROUND & AIMS: Fecal incontinence (FI) is characterized by uncontrolled passage of solid or liquid stool. We aimed to determine the prevalence and severity of FI in a large sample of US residents. METHODS: We recruited a representative sample of patients in October 2015 to complete the National Gastrointestinal (GI) Survey; a mobile app called MyGiHealth was used to systematically collect data on GI symptoms. FI was defined as accidental leakage of solid or liquid stool. Severity of FI was determined by responses to the National Institutes of Health FI Patient Reported Outcomes Measurement Information System questionnaire. Multivariable regression models were used to identify factors associated with FI prevalence and severity. RESULTS: Among 71,812 individuals who completed the National GI Survey, 14.4% reported FI in the past; of these, 33.3% had FI within the past 7 days. Older age, male sex, and Hispanic ethnicity increased the likelihood of having FI within the past week. Individuals with Crohn's disease, ulcerative colitis, celiac disease, irritable bowel syndrome, or diabetes were more likely to report FI. Non-Hispanic black and Hispanic individuals and individuals with Crohn's disease, celiac disease, diabetes, human immunodeficiency virus/acquired immunodeficiency syndrome, or chronic idiopathic constipation had more severe symptoms of FI than individuals without these features. CONCLUSIONS: In a large population-based survey, 1 in 7 people reported previous FI. FI is age-related and more prevalent among individuals with inflammatory bowel disease, celiac disease, irritable bowel syndrome, or diabetes than people without these disorders. Proactive screening for FI among these groups is warranted.

Who is Responsible for What Happens Before, During, and After Colonoscopy? Results of a National Survey of Primary Care Physicians.

BACKGROUND AND AIMS: Primary care providers (PCPs) play a critical role in colon cancer screening by initiating referrals to gastroenterologists for colonoscopy, but little is known about their role in pre-colonoscopy bowel preparation selection and pre-colonoscopy follow-up care. This study aimed to better understand coordination of care between PCPs and gastroenterologists as well as the current availability of "open-access" screening colonoscopy. METHODS: A multiple-choice survey was developed to assess PCPs' experiences with open-access colonoscopy, their involvement in the pre-colonoscopy process, and follow-up after colonoscopy. The survey was distributed electronically to a nationally representative sample of PCPs, via the American College of Physicians (ACP) Research Center's Internal Medicine Insider Research Panel. RESULTS: Of 442 PCPs invited to participate, 210 responded (response rate, 210/442, 48%), and 29 were ineligible (spent <25% of their time on clinical care or placed no referrals to colonoscopy), yielding 181 completed surveys. A total of 39% reported that open access was "rarely" or "never" available in their practice setting. The majority reported that pre-colonoscopy care was coordinated by gastroenterologists rather than PCPs. For example, 93% reported that gastroenterologists were responsible for bowel preparation selection in their practice setting. Post-colonoscopy, 54% of PCPs reported that they were responsible for ordering subsequent colonoscopies. CONCLUSIONS: PCPs frequently coordinate follow-up care postprocedure but play a relatively minor role in the pre-colonoscopy bowel preparation process. Open access availability for screening colonoscopy remains limited in this national sample of PCPs.

Factors Associated with Surveillance Adenoma and Sessile Serrated Polyp Detection Rates.

BACKGROUND: Adenoma detection rate (ADR) and sessile serrated polyp detection rate (SSPDR) data in surveillance colonoscopy are limited. AIMS: Our aim was to determine surveillance ADR and SSPDR and identify associated predictors. METHODS: A retrospective review of subjects who underwent surveillance colonoscopy for adenoma and/or SSP at an academic center was performed. The following exclusion criteria were applied: prior colonoscopy ≤ 3 years, incomplete examination, or another indication for colonoscopy. Patient, endoscopist, and procedure characteristics were collected. Predictors were identified using multivariable logistic regression. RESULTS: Of 3807 colonoscopies, 2416 met inclusion criteria. Surveillance ADR was 49% and, SSPDR was 8%. Higher ADR was associated with: age per year (OR 1.03; 95% CI 1.02-1.04), male gender (OR 1.55; 95% CI 1.29-1.88), BMI per kg/m2 (OR 1.02; 95% CI 1.01-1.04), withdrawal time per minute (OR 1.09; 95% CI 1.07-1.10), and endoscopists' screening ADR (OR 1.01; 95% CI 1.00-1.03). Years since training (OR 0.99; 95% CI 0.98-0.99) was associated with lower ADR. Family history of CRC (OR 1.58; 95% CI 1.02-2.27) and endoscopists' screening ADR (OR 1.40; 95% CI 1.15-1.74) were associated with higher SSPDR. African-American race (OR 0.36; 95% CI 0.10-0.75) and diabetes (OR 0.41; 95% CI 0.21-0.76) were associated with lower SSPDR. CONCLUSIONS: For surveillance colonoscopy, nearly half of patients had an adenoma and one in twelve had an SSP. In addition to established factors, BMI, endoscopists' screening ADR, and years since training were associated with ADR, whereas African-American race and diabetes were inversely associated with SSPDR. Further studies are needed prior to integrating surveillance ADR and SSPDR into quality metrics.