254 Delays in Colonoscopy Start Times Are Associated With Reductions in Adenoma Detection Rate

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Screening Colonoscopy and the Risk of Death From Right and Left Colon Cancers Chyke A. Doubeni, Douglas Corley, Virginia P. Quinn, Christopher D. Jensen, Ann G. Zauber, Michael Goodman, Jill Johnson, Shivan J. Mehta, Tracy Becerra, Wei K. Zhao, Joanne E. Schottinger, V. Paul Doria-Rose, Theodore R. Levin, Noel Weiss, Robert Fletcher

Risk of Advanced Adenoma, Colorectal Cancer, and Colorectal Cancer Mortality in Individuals With Low Risk Adenomas on Baseline Colonoscopy: A Systematic Review and Meta-Analysis Catherine Dube, Mafo Yakubu, Bronwen McCurdy, Andrea Lischka, Jill Tinmouth BACKGROUND: Guidelines differ on the recommended management of individuals with low risk adenomas (LRA) defined as 1-2 tubular adenomas <10 mm without high grade dysplasia at baseline colonoscopy. A systematic review and meta-analysis was conducted to examine the evidence on the relative risk of advanced adenomas (AA), colorectal cancer (CRC), and CRC mortality in individuals with LRA on baseline colonoscopy compared with those with a normal colonoscopy or the general population. METHODS: PubMed and EMBASE were searched from 2006 to July 2015 for peer-reviewed, English-language, comparative studies reporting outcomes of interest assessed at least 3 years after the baseline colonoscopy. The quality of the studies and body of evidence were assessed using the Newcastle-Ottawa scale and GRADE, respectively. RESULTS: Eleven observational studies (N=68,263) with follow-up of persons with LRA ranging from 3-19 years were included. The comparator was either persons with normal colonoscopy (8 studies) or the general population (3 studies). Studies comparing to those with normal colonoscopy : A meta-analysis of 8 cohort studies (N=10,139, follow-up range: 3-10 years) showed a small but statistically significant increase in the incidence of AA in individuals with LRA compared to those with a normal colonoscopy (RR 1.55, 95% CI 1.24-1.94, P=0.0001, I2=0%). The studies that compared the risk of CRC or CRC-related mortality in the LRA versus normal colonoscopy groups could not be pooled due to differences in study design. Studies comparing to the general population: Two studies showed a reduction in the risk of CRC in the LRA group compared with the general population. The cohort study reported a 32% reduction in CRC incidence after a median of 7.7 years of follow-up (SIR 0.68, 95% CI 0.44-0.99). The casecontrol study found a 60% reduction in the odds of CRC after 3-5 years (OR 0.4, 95% CI 0.2-0.6); however, the reduction in CRC observed at 6-10 years was not significant (OR 0.8, 95% CI 0.4-1.5). Finally, one large retrospective cohort found a 25% reduction in CRC mortality in individuals with LRA compared with the general population (SMR 0.75, 95% CI 0.63-0.88, median follow-up 7.7 years). While the individual studies were of moderate quality based on the Newcastle-Ottawa scale, the overall GRADE quality of evidence is low. CONCLUSION: While a small but significant increase in the risk of AA was observed in people with LRA compared to those with a normal colonoscopy, the clinical importance of this finding is unknown. On the other hand, the risk of CRC and of CRC-related mortality in the LRA group compared with the general population is significantly reduced. These findings support recent European guidelines that individuals with LRA at baseline colonoscopy return to average risk screening as opposed to more intensive colonoscopy surveillance.

Background: The effectiveness of endoscopic screening in reducing mortality risk from colorectal cancers (CRC) in the left side of the colon has been established by randomized controlled trials (RCT), but effectiveness for right colon cancers remains unclear. Findings from observational studies of colonoscopy's effect in the right colon are conflicting and have methodological limitations. Study Aims: The primary aim of this study was to determine whether, in average-risk people, receipt of screening colonoscopy, compared with not receiving screening endoscopy, reduces the risk of dying from right colon cancer. We also estimated colonoscopy's effect in the left colon/rectum. As an external validation, we estimated the magnitude of the mortality reduction associated with sigmoidoscopy in our data to compare with the 37-43% overall CRC mortality reduction of once-only screening sigmoidoscopy reported in RCTs. Methods: We conducted a case-control study in Kaiser Permanente, Northern and Southern California. The study population was members with ‡5 years of health enrollment without a prior history of CRC diagnosis, colectomy, inflammatory bowel disease, familial CRC, or heritable CRC syndrome. Cases were patients who were 55-90 years old on the date of death from CRC during 2006-2012; the CRC diagnosis date (reference date) was used to ascertain eligibility and exposure status. Cases were matched to controls on birthdate, sex, prior health plan enrollment duration, and medical service area. Screening exposures were measured in the 10-year period before the reference date by chart audits and expert adjudication. The primary exposure of interest was receipt of screening colonoscopy; sigmoidoscopy was of secondary interest. The outcome was death from colorectal adenocarcinoma as the underlying cause, overall and by location. Results: A total of 5,261 eligible patients (1,758 cases and 3,503 matched controls) were analyzed. Overall, 1.4% of case patients and 3.5% of controls had received screening colonoscopy. In multivariable conditional regression analyses, we found an adjusted odds ratio of 0.31 (95% confidence interval [CI], 0.19-0.50) for any CRC death (see Table). For right colon cancers, the adjusted odds ratio was 0.35 (CI: 0.18-0.66) and for left colon/rectum tumors, the adjusted odds ratio was 0.22 (CI: 0.10-0.48). In the analysis of screening sigmoidoscopy and the risk of death from any CRC, we found an adjusted odds ratio of 0.60 (CI: 0.51- 0.70). Conclusions: Receipt of screening colonoscopy was associated with a substantially reduced risk of death from both right and left colon cancers. The comparability of our estimates for screening sigmoidoscopy with RCT results supports the validity of our findings. Association between receipt of screening colonoscopy or sigmoidoscopy and colorectal cancer death risk, overall and according to location

253 Natural Language Processing Accurately Calculates Adenoma and Sessile Serrated Polyp Detection Rates Jennifer Nayor, Sergey Goryachev, Vivian S. Gainer, John R. Saltzman Background and Aim: Adenoma detection rate (ADR) is a measure of colonoscopy quality that is correlated with interval colon cancer occurrence. ADR calculations are often done with manual chart review, which is labor intensive. Natural language processing (NLP) is a computer-based linguistics technique that can extract meaning from free text based reports. The aim of this project was to calculate ADRs using NLP on data stored in a widely used electronic health record system (EPIC) and colonoscopy reporting system (Provation). Methods: A Provation query was used to identify patients who underwent a screening colonoscopy between June 2010 and August 2015. Pathology reports within Epic were transferred to an institutional data repository and then linked to the colonoscopy reports of the patients identified by the Provation query. An NLP algorithm was created to identify adenomas, sessile serrated polyps (SSP) and adenocarcinomas in these pathology reports. Three developmental iterations were used to maximize the NLP performance. ADRs and SSP detection rates (SDR) were then calculated overall and for individual endoscopists. Results: 8,480 screening colonoscopies identified in Provation were linked to 4,005 pathology reports from Epic (47.2%). Manual chart review was conducted on a derivation set of 500 pathology reports and a validation set of 100 pathology reports. The derivation and validation sets had accuracy of 100% for adenomas, 100% for SSPs and 100% for adenocarcinomas. The mean total ADR was 24.7% (range 14.7-53.2%); mean male ADR was 32.9 (range 19.762.9%); and mean female ADR was 23.5% (range 9.1-51.0%). The mean SDR was 3.4% (range 1.0-9.6%). Conclusions: NLP can accurately report ADR and SDR using data stored in the Epic electronic health record and Provation colonoscopy reporting systems.

254 Delays in Colonoscopy Start Times Are Associated With Reductions in Adenoma Detection Rate Monika Laszkowska, Srihari Mahadev, Peter H. Green, Benjamin Lebwohl

Note: Model includes indicators for screening sigmoidoscopy and excluded 51 patients (10 cases, 41 controls) who had been screened by sigmoidoscopy prior to a documented screening colonoscopy. Model adjusted for race/ethnicity, family history (not verified to meet exclusion criteria), % of people 25+ years in the census tract with a high school diploma (in quartiles), Charlson score, no healthcare visit, and number of visits to a primary care provider.

Background: Delays in endoscopy suites impact patient satisfaction and healthcare efficiency. Prior investigations of the impact of delays on adenoma detection rates (ADRs) have not found a significant association, though these studies included modest delays, with few cases delayed by more than one hour. We aimed to measure the impact of delays in start times of screening colonoscopies on the outcome measures of bowel preparation quality and ADR. Methods: In this single center, retrospective cohort study, we queried the electronic endoscopy record for all screening colonoscopies performed from Jan. 1, 2011 through June 30, 2015. We collected data on both scheduled and actual case start time, adenoma detection rate, and preparation quality. Using multivariate logistic regression, we measured the impact of delays on preparation quality and ADR, adjusting for age and gender. Results: Of 8,546 screening colonoscopies, 898 (11%) started on time or early and 2669 (31%) were delayed by >1 hour. The mean delay was 53 minutes. Results were divided into 3 categories based on delay times: 0-1 hour (n=5877), 1-2 hours (n=2159), and >2 hours (n=510). As delay increased, there was an increase in the proportion of cases with suboptimal bowel preparations

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(0-1hr=19%, 1-2hr=20%, >2hr=25%; p=0.01). When delays were stratified by procedures done in the morning (before noon) vs. afternoon, this trend had a significant impact on morning cases (0-1hr=18%, 1-2hr=16%, >2hr=26%; p=0.001) but not afternoon cases (01hr=22%, 1-2hr=26%, >2hr=23%; p=0.16). Overall, morning cases had a lower proportion with suboptimal bowel preparation than afternoon cases (18% vs. 24%, p<0.01). When adjusting for age and gender, there was a significant increase in suboptimal preparation with delays >2hrs (OR 1.35, CI 1.09-1.67, p=0.006). This effect diminished when adjusting for time of day of the procedure (morning vs. afternoon) (OR 1.23, CI 0.99-1.53, p=0.058). Similarly, there was a significant decrease in ADR as delay time increased (0-1hr=24%, 12hr=21%, >2hr= 21%; p=0.01). This effect was more seen in morning cases (0-1hr=24%, 1-2hr=21%, >2hr=19%; p=0.018) but not afternoon cases (0-1hr=25%, 1-2hr=22%, >2hr= 23%; p=0.288). There was no difference in ADR between morning and afternoon procedures overall (23% for both, p=0.53). When adjusting for age, gender, and time of day of the procedure there was a significant decrease in ADR with delays of 1-2hrs (OR 0.82, CI 0.720.96, p=0.001) and >2hrs (OR 0.77, CI 0.62-0.97, p=0.025). Conclusions: Delays >1 hour have a significant deleterious impact on ADR, independent of time of day of the procedure. Furthermore, delays >2 hours impact preparation quality, particularly in afternoon cases. Delays appear to cause a reduction in colonoscopy quality, and efforts should be made to minimize delays for screening colonoscopies.

or probably (29%) be willing to delay their own colonoscopy. In multivariable analysis, factors that predicted greater willingness to wait were: (1) better self-reported health (OR: 3.65; 95% CI: 1.29-10.3); (2) greater trust in physician (OR: 1.40; 95% CI: 1.24-1.58). Factors that predicted less willingness to wait were: (1) lower health literacy (OR: 0.29; 95% CI: 0.13-0.64); (2) greater perceived threat of CRC (OR: 0.88; 95% CI: 0.83-0.93); (3) nonwhite race (OR: 0.39; 95% CI: 0.24-0.62). Conclusion: Despite having a strong personal interest in repeat screening, previously screened patients were almost universally willing to delay their own screening colonoscopy for higher risk patients. Appealing to altruism could be effective in situations where scarce resources must be utilized wisely.

257 Assessment of Anti-Vinculin and Anti-CdtB Antibodies in IBS Subtypes Ali Rezaie, Walter Morales, Emily Marsh, Anthony Lembo, Jae Hak Kim, Stacy Weitsman, Kathleen Shari Chua, Gillian Barlow, Mark Pimentel IBSchek® is a new blood test that differentiates IBS-D from other causes of diarrhea (PlosOne, 2015) based on antibodies to cytolethal distending toxin B (CdtB, a toxin found in bacteria that cause acute gastroenteritis) and autoantibodies to vinculin (a human protein involved in focal adhesion plaques and important to enteric neuronal development). In this study, we examined the potential importance of these antibodies in other IBS subtypes. Methods IBS-D subjects were recruited from a large-scale multicenter clinical trial for IBS-D (TARGET 3). Healthy subjects without functional or gastrointestinal symptoms as well as subjects with IBS-M and IBS-C (defined by Rome III Criteria) were recruited from two major medical centers. Plasma levels of anti-CdtB and anti-vinculin antibodies were determined by ELISA, and compared between groups. Optical density levels of ‡1.68 and 2.8 were considered positive for anti-vinculin and anti-CdtB, respectively. After normalization of data, the mean value of each antibody was assessed between groups. A one-way analysis of variance with pairwise Bonferroni comparison was used to compare the levels and positivity rates of antibodies among the groups. Strength and direction of association was assessed using Spearman's and Point-Biserial correlation. Results Age and gender were similar among the IBS-D subjects (n=2375), IBS-M (n=25) IBS-C (n=30) and healthy controls (n=43). Plasma levels of anti-CdtB and anti-vinculin antibodies were highest in IBS-D (compared to all other groups individually or collectively, P<0.00001) and lowest in healthy individuals (Figure 1). Plasma levels was slightly higher in IBS-C than healthy individuals though not statistically different (p>0.1). Antibody levels had a statistically significant negative gradient from IBSD to IBS-M, IBS-C and healthy individuals (anti-CdtB rho=-0.17; anti-vinculin rho=-0.07; p<0.001). Based on the definition of a positive test (anti-CdtB ‡2.80 and anti-vinculin‡1.68 OD), there was a significant gradient in results such that the test was helpful in identifying IBS-D and IBS-M, but not IBS-C. Antibody levels were independent of age and gender (p>0.1). Conclusions Plasma levels of anti-CdtB and anti-vinculin antibodies vary depending on the subtype of IBS, with the highest levels in IBS-D followed by IBS-M, while IBS-C has similar levels to healthy individuals. Since these antibodies are important in the pathophysiology of IBS-D and now IBS-M, this may suggest a different pathophysiology for IBS-C.

255 A Targeted Colonoscopy Preparation Strategy to Reduce Preparation Failure: Results of a Decision Analysis Jacob E. Kurlander, Shahnaz Sultan, Sameer D. Saini Objectives: Failed colonoscopy bowel preparation is common, costly, and clinically harmful, resulting in a higher risk of complications, longer procedure times, and lower polyp detection rates. Patients who fail a standard bowel preparation require repeat colonoscopy with highvolume, 2-day preparation. Prediction models can identify patients at risk for preparation failure, in whom 2-day preparation could be used up-front (a "targeted" strategy), potentially reducing the burden associated with having to repeat the bowel preparation and colonoscopy. But this strategy is rarely used in practice. Methods: We developed a Markov decision analytic model to compare usual care to a targeted bowel preparation strategy. Usual care consisted of initial 4-liter split-dose preparation, with 2-day preparation only for those who failed initial preparation. The targeted strategy consisted of standard 4-liter preparation for patients at low risk for preparation failure, and up front 2-day preparation for those at high risk. Base-case values and ranges for input variables were gathered from literature review. Under each strategy, we calculated number of days spent preparing for, or undergoing, colonoscopy (a measure of "patient burden"), and cost of care per patient (payer perspective). Sensitivity analyses were performed to identify the effect of varying model inputs on the outcomes. Results: In the base-case analysis, the targeted strategy resulted in a similar number of days spent preparing for or undergoing colonoscopy compared to usual care (2.56 vs 2.51 days, respectively). However, it substantially reduced the cost per patient ($1,243 vs $1,334) by reducing the number of colonoscopies performed. In sensitivity analyses, the targeted strategy was cost saving across the entire plausible range of preparation failure risk and prediction model sensitivity and specificity. The targeted strategy resulted in less patient burden than the usual care strategy when: (1) the risk of preparation failure exceeded 20% (base case: 17%); (2) prediction model sensitivity exceeded 73% (base case: 59%); or, (3) prediction model specificity exceeded 76% (base case: 59%). The effectiveness of two-day bowel preparation among patients who had failed standard bowel preparation had no effect on model results. In probabilistic sensitivity analysis, patient burden remained similar between the targeted strategy and usual care, but cost was lower with the targeted strategy in > 99% of trials. Conclusions: Using existing prediction models, a targeted bowel preparation strategy is likely to save costs by reducing the number of repeat colonoscopies for preparation failure, with minimal effect on the amount of time patients can expect to spend preparing for or undergoing colonoscopy. This strategy merits further study, including investigation of patient acceptability.

256 Patients' Willingness to Share Limited Endoscopic Resources: Results of a Large Regional Survey Marc S. Piper, Val Metko, Jacob E. Kurlander, Brian J. Zikmund-Fisher, Jennifer K. Maratt, Akbar K. Waljee, Sameer D. Saini

The percentage of patients with positive antibody testing among the IBS subtypes and healthy controls

Background: In some health systems, patients face long wait times for elective endoscopic procedures. For such procedures, patients are typically scheduled using a "first come, first serve" approach. But this approach may lead to delayed procedures for higher risk patients. One alternative is to use state-of-the-art prediction models to prioritize scheduling according to risk. Yet, we know little about the acceptability of such an approach to patients. Patients and Methods: We developed a multiple-choice, scenario-based survey to elicit attitudes towards repeat screening colonoscopy. Potential survey participants were identified electronically using the endoscopic database at the VA Ann Arbor Healthcare System. We identified participants who met the following criteria: (1) age ‡ 50; (2) prior complete, normal averagerisk screening colonoscopy with adequate bowel preparation. Individuals were excluded if they had a personal or family history of colon cancer or adenomas, or a personal history of inflammatory bowel disease (IBD). We examined a subgroup of questions about attitudes towards risk-based prioritization of colonoscopy scheduling. Specifically, we asked respondents whether they would be willing to wait up to 6 months to get a repeat screening colonoscopy so that higher-risk patients could be screened first. Multivariable ordinal logistic regression was used to identify patients factors associated with greater willingness to wait. Results: 1,054 of 1,500 possible respondents completed the survey (72%). Respondents were predominantly white (86%) and male (94%). The median age was 60-69 years. Many patients (46%) were eager to undergo screening colonoscopy, reporting that they would want a screening colonoscopy even if they had serious, life-limiting health problems and a physician recommendation to stop screening. Despite this, patients reported a strong willingness to delay their own colonoscopy so that another, higher-risk patient could undergo colonoscopy sooner. Specifically, 94% of respondents stated they would definitely (65%)

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FODMAPs Alter the Metabolome and Symptoms in Irritable Bowel Syndrome Patients Stephen Vanner, Keith McIntosh, David E. Reed, Teresa Schneider, Frances Dang, Ammar H. Keshteli, Giada de Palma, Karen Madsen, Premysl Bercik Background and aims: FODMAPs (fermentable oligo-, di-, and mono-saccharides and polyols) in the diet can induce IBS symptoms but the mechanism(s) are poorly understood. We used low and high FODMAP diets to examine how changes in the metabolome might underlie alterations in symptoms of the irritable bowel syndrome (IBS). Methods: We performed a randomized controlled, double-blind study of IBS patients who met the ROME III criteria. Patients were randomized to a low (n = 20) or high (n = 20) FODMAP diet for 3 weeks and maintained a food diary for this period. Changes in symptoms were assessed using the IBS severity scoring system (IBS-SSS). The metabolome was evaluated by comparing baseline and post diet measurements using the lactulose breath test (LBT), metabolic profiling in urine using direct infusion (DI-MS) and gas chromatography mass spectrometry (GCMS), and partial 16S rRNA gene profiling (Illumina) to analyze stool microbiota composition. Results: Thirty-seven patients (19 low FODMAP; 18 high FODMAP) completed the 3 week diet. The IBS-SSS was reduced in the low FODMAP group (P<0.001) but not the high FOMAP group. Metabolic profiling of urine showed both patient groups were similar at baseline but differed significantly after the 3 week diet (p<0.01). Three metabolites (histamine, p-hydroxybenzoic acid, azelaic acid) were primarily responsible for discrimination between

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