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BACKGROUND Models estimating risk for advanced proximal colorectal neoplasia (APN) may be used to select colorectal cancer (CRC) screening test, either prior to knowing distal colorectal findings or afterward. Current models have only fair discrimination and nearly all require knowing distal findings. OBJECTIVE Derive and test risk prediction models for APN with and without distal findings. SETTING Selected endoscopy centers within central Indiana, USA. PARTICIPANTS Average-risk persons undergoing first-time screening colonoscopy. INTERVENTIONS Demographics, personal and family medical history, lifestyle factors and physical measures were linked to the most advanced finding in proximal and distal colorectal segments. For both models, logistic regression identified factors independently associated with APN on a derivation set. Based on equation coefficients, points were assigned to each factor, and risk for APN was examined for each score. Scores with comparable risks were collapsed into risk categories. Both models and their scoring systems were tested on the validation set. MAIN OUTCOME APN, defined as any adenoma or sessile serrated lesion ≥1 cm, one with villous histology or high-grade dysplasia, or CRC proximal to the descending colon. RESULTS Among 3025 subjects in the derivation set (mean age 57.3 ± 6.5 years; 52% women), APN prevalence was 4.5%; 2859 (94.5%) had complete data on risk factors. Independently associated with APN were age, sex, cigarette smoking, cohabitation status, metabolic syndrome, non-steroidal anti-inflammatory drug use and physical activity. This model (without distal findings) was well-calibrated (P = 0.62) and had good discrimination (c-statistic = 0.73). In low-, intermediate- and high-risk groups that comprised 21, 58 and 21% of the sample, respectively, APN risks were 1.47% (95% CI, 0.67-2.77%), 3.09% (CI, 2.31-4.04%) and 11.6% (CI, 9.10-14.4%), respectively (P

Identifying risk factors for early onset colorectal cancer (EOCRC) could help reverse its rising incidence through risk factor reduction and/or early screening. We sought to identify EOCRC risk factors that could be used for decisions about early screening. Using electronic databases and medical record review, we compared male veterans aged 35-49 years diagnosed with sporadic EOCRC (2008-2015) matched 1:4 to clinic and colonoscopy controls without CRC, excluding those with established inflammatory bowel disease, high-risk polyposis and non-polyposis syndromes, prior bowel resection, and high-risk family history. We ascertained sociodemographic and lifestyle factors, family and personal medical history, physical measures, vital signs, medications, and laboratory values 6-18 months prior to case diagnosis. In the derivation cohort (75% of the total sample), univariate and multivariate logistic regression models were used to derive a full model and a more parsimonious model. Both models were tested using a validation cohort. Among 600 cases of sporadic EOCRC (mean [SD] age 45.2 [3.5] years; 66% White), 1200 primary care clinic controls (43.4 [4.2] years; 68% White), and 1200 colonoscopy controls (44.7 [3.8] years; 63% White), independent risk factors included age, cohabitation and employment status, BMI, comorbidity, CRC or other visceral cancer in a first- or second-degree relative; alcohol use; exercise; hyperlipidemia; use of statins, NSAIDs, and multivitamins. Validation c-statistics were 0.75-0.76 for the full model and 0.74-0.75 for the parsimonious model, respectively. These independent risk factors for EOCRC may identify veterans for whom CRC screening prior to age 45 or 50 years should be considered.

Data supporting the clinical utility of multi-target stool DNA (mt-sDNA) at the guideline-recommended 3-year interval have not been reported.Between April 2015 and July 2016, candidates for colorectal cancer screening whose providers prescribed the mt-sDNA test were enrolled. Participants with a positive baseline test were recommended for colonoscopy and completed the study. Those with a negative baseline test were followed annually for 3 years. In year 3, the mt-sDNA test was repeated and colonoscopy was recommended independent of results. Data were analyzed using the Predictive Summary Index (PSI), a measure of the gain in certainty for dichotomous diagnostic tests (where a positive value indicates a net gain), and by comparing observed versus expected colorectal cancers and advanced precancerous lesions.Of 2,404 enrolled subjects, 2,044 (85%) had a valid baseline mt-sDNA result [284 (13.9%) positive and 1,760 (86.1%) negative]. Following participant attrition, the year 3 intention to screen cohort included 591 of 1,760 (33.6%) subjects with valid mt-sDNA and colonoscopy results, with no colorectal cancers and 63 advanced precancerous lesions [22 (34.9%) detected by mt-sDNA] and respective PSI values of 0% (P = 1) and 9.3% (P = 0.01). The observed 3-year colorectal cancer yield was lower than expected (one-sided P = 0.09), while that for advanced precancerous lesions was higher than expected (two-sided P = 0.009).Repeat mt-sDNA screening at a 3-year interval resulted in a statistically significant gain in detection of advanced precancerous lesions. Due to absence of year 3 colorectal cancers, the PSI estimate for colorectal cancer was underpowered and could not be reliably quantified. Larger studies are required to assess the colorectal cancer study findings.Prevention Relevance:Understanding the 3-year yield of mt-sDNA for colorectal cancer and advanced precancerous polyps is required to ensure the clinical appropriateness of the 3-year interval and to optimize mt-sDNA's screening effectiveness.

Supplemental Table S1: Distribution of colorectal lesions among subjects at baseline (T0) and year 3 (T3). Supplemental Table S2: Study subject accountability in the baseline negative population

This Supplemental Text file provides additional information regarding the clinical procedures and sample processing/lab procedures, as well as an explanation of the sensitivity and robustness analyses.

High-specificity colorectal cancer screening is desirable to triage patients P = 0.75) or race (P = 0.36) in participants with NAA or negative findings. Sensitivity for APL was 32.7% (CI, 19.9–47.5%), with most APL (83.7%) measuring 10–19 mm and none having high-grade dysplasia. The area under the ROC curve for discriminating between APL and lesser findings was 0.72 (CI, 0.64–0.81). mt-sDNA's high specificity would help minimize risk from unnecessary diagnostic procedures in this age group. This study shows that mt-sDNA has high specificity among average-risk 45 to 49-year olds, supporting its use as a noninvasive option for colorectal cancer screening.Prevention Relevance:This study shows that mt-sDNA has high specificity among average-risk 45–49 year olds, supporting its use as a non-invasive option for colorectal cancer screening.

Supplementary Tables

Background: Identifying patients who benefit from screening prior to ages 45 or 50 through risk-prediction models may improve the uptake and effectiveness of colon cancer (CRC) screening. “Colon Age” is a way to estimate a person’s risk for CRC in Veterans younger than age 50. The purpose of this study is to determine what patients and primary care providers think about the “Colon Age” concept in terms of its comprehensibility, acceptability, and utility for decision-making about CRC screening. Methods: Veteran patients < 50 years old and primary care providers (PCPs) were recruited from the Roudebush VAMC’s outpatient clinics. Semi-structured, qualitative interviews were conducted one-on-one and included Likert-scale and open-ended questions. The estimate of colon age is based on relating a person’s individual features to the 5-year age group in the U.S. population of men with the closest risk of CRC based on Surveillance, Epidemiology, and End Result cancer incidence data. Results: 19 patients and 8 PCPs were recruited. The majority of patients (68%) had a colon age below that of their biological age, while 2 of 19 (11%) had a higher colon age. PCPs identified the tool’s potential to promote screening uptake, facilitate discussion between patients and PCPs, and adhere to current practices as facilitators. Identified barriers among PCPs and patients included questions about tool accuracy and validation, patient reluctance to receive any form of screening, and limited perceived utility for patients between the ages 45-49. Conclusions and Potential Impact: Using the concept of colon age to express individual patient risk for early-onset CRC was well-received among almost all veteran patients and physicians interviewed.Colon-age adapted screening tools should be incorporated into theelectronic health record reminders to facilitate decision-making and screening uptake.Colon-age based personalized screening has the potential to improve cancer detection by providing individualized recommendations.

Data supporting the clinical utility of multi-target stool DNA (mt-sDNA) at the guideline-recommended 3-year interval have not been reported. Between April 2015 and July 2016, candidates for colorectal cancer screening whose providers prescribed the mt-sDNA test were enrolled. Participants with a positive baseline test were recommended for colonoscopy and completed the study. Those with a negative baseline test were followed annually for 3 years. In year 3, the mt-sDNA test was repeated and colonoscopy was recommended independent of results. Data were analyzed using the Predictive Summary Index (PSI), a measure of the gain in certainty for dichotomous diagnostic tests (where a positive value indicates a net gain), and by comparing observed versus expected colorectal cancers and advanced precancerous lesions. Of 2,404 enrolled subjects, 2,044 (85%) had a valid baseline mt-sDNA result [284 (13.9%) positive and 1,760 (86.1%) negative]. Following participant attrition, the year 3 intention to screen cohort included 591 of 1,760 (33.6%) subjects with valid mt-sDNA and colonoscopy results, with no colorectal cancers and 63 advanced precancerous lesions [22 (34.9%) detected by mt-sDNA] and respective PSI values of 0% (P = 1) and 9.3% (P = 0.01). The observed 3-year colorectal cancer yield was lower than expected (one-sided P = 0.09), while that for advanced precancerous lesions was higher than expected (two-sided P = 0.009). Repeat mt-sDNA screening at a 3-year interval resulted in a statistically significant gain in detection of advanced precancerous lesions. Due to absence of year 3 colorectal cancers, the PSI estimate for colorectal cancer was underpowered and could not be reliably quantified. Larger studies are required to assess the colorectal cancer study findings. Prevention Relevance: Understanding the 3-year yield of mt-sDNA for colorectal cancer and advanced precancerous polyps is required to ensure the clinical appropriateness of the 3-year interval and to optimize mt-sDNA's screening effectiveness.

BACKGROUND AND GOALS There is variation in polypectomy techniques for resection of small polyps. Aim was to compare techniques for 4 to 6 mm polyps for recurrent adenoma, efficiency, and adverse events and to establish methodological factors for definitive trial. MATERIALS AND METHODS The study was a randomized controlled trial. Outpatients with ≥1, 4 to 6 mm polyps were randomized to cold forceps (CF), cold snare (CS), and hot snare (HS). Polypectomy site was marked with SPOT to assess for recurrence at the original polypectomy site during surveillance colonoscopy. To assess feasibility of a definitive trial we measured (1) rates of patient refusal, participation, ineligibility; (2) retention; (3) recurrent neoplasia; and (4) sample size for a definitive trial. RESULTS Three hundred fifty-three patients were randomized to 1 of the 3 polypectomy techniques, of whom 260 (73.6%) completed the initial colonoscopy (mean age 57 y, 50.4% women), with 91, 87, and 82 patients randomized to CF, CS, and HS polypectomy, respectively. Mean time for polyp resection for CF, CS, and HS were 198.8, 58.5, and 96.8 seconds, respectively, with CS and HS requiring less time than CF (P

ImportancePostcolonoscopy colorectal cancer (PCCRC) refers to colorectal cancer (CRC) diagnosed after a colonoscopy in which no cancer was found and is reflective of colonoscopy quality at the individual and system levels. Colonoscopy is widely performed in the Veterans Affairs (VA) health care system, but the prevalence of PCCRC and its associated mortality are unknown.ObjectiveTo examine PCCRC prevalence and its all-cause mortality (ACM) and CRC-specific mortality (CSM) within the VA health care system.Design, Setting, and ParticipantsThis retrospective cohort study used VA-Medicare administrative data to identify 29 877 veterans aged 50 to 85 years with newly diagnosed CRC between January 1, 2003, and December 31, 2013. Patients whose colonoscopy occurred less than 6 months before CRC diagnosis with no other colonoscopy within the previous 36 months were categorized as having detected CRC (DCRC). Those who had a colonoscopy that did not detect CRC between 6 and 36 months before CRC diagnosis were categorized as having postcolonoscopy CRC (PCCRC-3y). A third group included patients with CRC and no colonoscopy within the prior 36 months. The final analysis of the data was performed in September 2022.ExposuresPrior receipt of colonoscopy.Main Outcomes and MeasuresCox proportional hazards regression (with censoring, last follow-up December 31, 2018) analyses were conducted to compare PCCRC-3y and DCRC for 5-year ACM and CSM after CRC diagnosis.ResultsOf 29 877 patients with CRC (median [IQR] age, 67 [60-75] years; 29 353 [98%] male; 5284 [18%] Black, 23 971 [80%] White, and 622 [2%] other), 1785 (6%) were classified as having PCCRC-3y and 21 811 (73%) as having DCRC. The 5-year ACM rates were 46% vs 42% for patients with PCCRC-3y vs patients with DCRC. The 5-year CSM rates were 26% vs 25% for patients with PCCRC-3y vs patients with DCRC. In multivariable Cox proportional hazards regression analysis, there was no significant difference in ACM and CSM between patients with PCCRC-3y (adjusted hazard ratio [aHR], 1.04; 95% CI, 0.98-1.11; P = .18) and patients with DCRC (aHR, 1.04; 95% CI, 0.95-1.13; P = .42). However, compared with patients with DCRC, patients with no prior colonoscopy had significantly higher ACM (aHR, 1.76; 95% CI, 1.70-1.82; P P P Conclusions and RelevanceThis study found that PCCRC-3y constituted 6% of CRCs in the VA system, which is similar to other settings. Compared with patients with CRC detected by colonoscopy, those with PCCRC-3y have comparable ACM and CSM.

Irritable bowel syndrome (IBS) in veterans is understudied. This study sought to investigate (1) prevalence of IBS; (2) phenotypic, environmental, and psychosocial factors associated with IBS; and (3) associations of IBS with health-related quality of life and health care use.From June 2018 to April 2020, we invited veterans to complete the Rome IV IBS questionnaire; Short Form-12; posttraumatic stress disorder (PTSD) checklist; Hospital Anxiety and Depression Scale; and questionnaires on general health, antibiotic use, infectious enteritis (IE), and health care use.Among 858 veteran respondents, 244 (28.4%) met Rome IV IBS criteria (47.5% IBS with diarrhea, 16.8% IBS with constipation, 33.6% mixed IBS). IBS was associated with greater anxiety and depression and lower quality of life (all P.001). Provisional PTSD, IE, and bowel problems after antibiotics were more common in IBS (all P.001) as were multiple doctor visits (P.01) and hospitalizations (P = .04). Comparisons across non-IBS and IBS subgroups revealed overall associations of psychological comorbidities (P.01), multiple doctor visits (P.01), hospitalizations (P = .03), IE (P.01), and bowel problems after IE (P = .03) or antibiotics (P.01) with subgroup. Highest anxiety and depression scores, PTSD, multiple doctor visits, hospitalizations, and bowel problems after IE were observed in IBS with constipation. In adjusted analyses, IBS was associated (all P.001) with anxiety (odds ratio [OR], 3.47), depression (OR, 2.88), lower quality of life, PTSD (OR, 3.09), IE (OR, 4.44), bowel problems after antibiotics (OR, 1.84), multiple doctor visits (OR, 2.08), and hospitalizations (OR, 1.78).IBS is prevalent among veterans and has a measurable impact on individuals and health care resources. Veterans with IBS may experience significant psychological impairment.

Risk stratification is a system by which clinically meaningful separation of risk is achieved in a group of otherwise similar persons. Although parametric logistic regression dominates risk prediction, use of nonparametric and semiparametric methods, including artificial neural networks, is increasing. These statistical-learning and machine-learning methods, along with simple rules, are collectively referred to as "artificial intelligence" (AI). AI requires knowledge of study validity, understanding of model metrics, and determination of whether and to what extent the model can and should be applied to the patient or population under consideration. Further investigation is needed, especially in model validation and impact assessment.

Background & Aims We aimed to compare the incidence of aerodigestive cancers in persons with negative results from colonoscopies and positive vs negative results from multitarget stool DNA tests for colorectal cancer and vs expected incidence. Methods We performed a retrospective cohort study of 1216 subjects with comprehensive patient records and/or cancer registry data from 3 medical centers in North America. Subjects had no neoplasia or only nonadvanced adenomas, based on screening colonoscopy, and either negative results (concordant with colonoscopy, n = 1011) or positive results (discordant colonoscopy, n = 205) from the multitarget stool DNA test. Outcomes included aerodigestive cancers in discordant vs concordant groups and comparison of observed aerodigestive cancer incidence between the groups and compared with expected incidence for the population, based on the Surveillance, Epidemiology, and End Results (SEER) data. Results Median follow-up times were comparable between subjects in the discordant (5.3 y; interquartile range, 3.5–5.8 y) and concordant (5.4 y; interquartile range, 3.7–5.8 y) groups. Aerodigestive cancers developed in 5 subjects in the discordant group vs 11 subjects in the concordant group (crude risk ratio, 2.3; 95% CI, 0.8–6.6; adjusted risk ratio, 2.2; 95% CI, 0.8–6.2; P = .151). The incidence of aerodigestive cancer was lower in the concordant group than the expected incidence based on SEER data (risk ratio, 0.4; 95% CI, 0.2–0.6; P = .0008). The incidence of aerodigestive cancer was not significantly greater in the population in the discordant group than the expected incidence based on SEER data (risk ratio, 0.8; 95% CI, 0.3–1.9; P = .599). Conclusions In a retrospective study with a median follow-up time of 5.4 years, incident aerodigestive cancers were uncommon among subjects with negative findings from colonoscopies, regardless of discordant or concordant results from multitarget stool DNA tests. Patients with negative results from high-quality colonoscopies therefore should not undergo further testing.

Several online calculators estimate colorectal cancer risk, but their consistency is unknown. Our objectives were to quantify the variation in predicted risk and to determine which calculators are best used in the clinical setting.We used the Google search engine to identify online colorectal cancer risk calculators and assessed each's output for 3 hypothetical screening scenarios (low-, average-, and high-risk), varied by age (50, 62, 75 years), sex, and race (Black, White), with risk levels based on risk-appropriate values for variables in each model. Estimated risks for models within a given scenario were rated as consistent or inconsistent based on comparison to either the absolute magnitude of difference or average lifetime risk of colorectal cancer. Summary statistics for consistent and inconsistent estimates were compared using Chi-square and Fisher's exact tests.We identified 5 online colorectal cancer risk calculators. Inconsistencies were found in none of 5-year, 19% of 10-year, and 81% of lifetime colorectal cancer risk estimate comparisons (p0.001). For a 50-year-old, 22% of risk estimate comparisons were inconsistent versus 33% for a 62-year-old, and 36% for a 75-year-old (p=0.14).Online colorectal cancer risk models are more consistent in predicting colorectal cancer risk for 5- and 10-year time frames compared to lifetime. For a U.S. population, the National Cancer Institute's Colorectal Cancer Risk Assessment Tool is a rigorously developed calculator that can be used in the clinical setting to provide 5-year and lifetime risk estimates.• Currently available colorectal cancer risk calculators are more consistent in estimating risk for shorter time frames than for longer time frames. • The methodology with which a model was developed, population of interest, and desired time frame for risk estimates should be considered when deciding which risk calculator to use for screening decision-making. • The National Cancer Institute Colorectal Cancer Risk Assessment Tool provides the most accurate estimates for a U.S.

Background: Medical evidence collected from new observational studies can sometimes significantly alter our understanding of disease incidence and progression. This requires efficient and accurate calibration of disease models to help quantify the differences between observed cohorts. However, in model calibration, it is common to encounter overfitting with many model parameters but few observational outcomes. Additionally, the difficulty in evaluating fitting performance is significant due to a large degree of outcome variation and expensive computations for even a single simulation run. Methods: We developed a two-phase calibration procedure to address the above challenges. As a proof-of-the-concept study, we verified the procedure with a discrete-event-simulation-based study on sex-specific colorectal neoplasia development. For the study, we estimated eight disease model parameters that govern colorectal adenoma incidence risk and growth rates at three distinct states: non-advanced, advanced adenoma, and adenoma becoming cancerous. For the calibration, we defined the likelihood measure by a relative weighted sum-of-squares difference between the three actual prevalence values reported in a recent publication and those predicted by a discrete-event colorectal cancer simulation. In phase I of the calibration procedure, we performed a series of low-dimensional sampling-based grid searches to identify reasonably good candidate parameter designs. In phase II, we performed a local search-based approach to further improve the model fit.Results: Overall, our two-phase procedure showed better goodness of fit than a straightforward implementation of the Nelder-Mead algorithm, yielding a 10-fold reduction in calibration error (0.0025 vs. 0.0251 for an all-white mixed-family-history male cohort on the likelihood measure defined above). Further, the two-phase procedure was more effective in calibrating a validated simulation model for a female cohort than a male cohort. Finally, in phase II, performing local search on each of the parameters sequentially is more effective than searching the entire parameter space simultaneously. Conclusions: The proposed two-phase calibration procedure is effective for estimating computationally expensive stochastic dynamic disease models. In addition, initial parameter search range truncation and sensitivity analysis on various parameters can be computationally cost-effective.

A process evaluation was conducted as part of a comparative effectiveness trial of a mailed interactive educational DVD intervention to promote colorectal cancer screening among average-risk patients who did not attend a scheduled colonoscopy. Participants (n = 371) for the trial were randomized to (1) mailed DVD, (2) mailed DVD plus patient navigation, or (3) usual care. Participants (n = 243) randomized to the two DVD intervention arms were called 2 weeks after mailing materials to complete a process evaluation interview about the DVD (September 2017–February 2020). Forty-nine (20%) participants were not reached, and 194 (80%) participants watched the DVD and completed the interview. The process evaluation assessed whether (1) the DVD content was helpful, (2) any new information was learned by participants, (3) the appropriate amount of information was included in the DVD, (4) participants were engaged when watching the DVD, (5) the DVD content was relevant, (6) participants were satisfied with the DVD (7) participants would recommend the DVD to others, and (8) their opinion about colorectal cancer screening was changed by watching the DVD. Among participants who watched the DVD, 99% reported the screening information was very or somewhat helpful, 47% learned new information, 75% said the DVD included the right amount of information, they were engaged (M = 3.35 out of 4, SD = 0.49), 87% reported all or most information applied to them, they were satisfied (M = 3.42 out of 4, SD = 0.39) with DVD content, 99% would recommend the DVD to others, and 45% reported changing their opinion about screening. To understand the effects of interventions being tested in trials and to plan the dissemination of evidence-based interventions, process evaluation is critical to assess the dose received and acceptability of behavioral interventions.

In 2018, the American Gastroenterological Association's Center for GI Innovation and Technology convened a consensus conference, entitled "Colorectal Cancer Screening and Surveillance: Role of Emerging Technology and Innovation to Improve Outcomes." The conference participants, which included more than 60 experts in colorectal cancer, considered recent improvements in colorectal cancer screening rates and polyp detection, persistent barriers to colonoscopy uptake, and opportunities for performance improvement and innovation. This white paper originates from that conference. It aims to summarize current patient- and physician-centered gaps and challenges in colonoscopy, diagnostic and therapeutic challenges affecting colonoscopy uptake, and the potential use of emerging technologies and quality metrics to improve patient outcomes.

Background Medical evidence from more recent observational studies may significantly alter our understanding of disease incidence and progression, and would require recalibration of existing computational and predictive disease models. However, it is often challenging to perform recalibration when there are a large number of model parameters to be estimated. Moreover, comparing the fitting performances of candidate parameter designs can be difficult due to significant variation in simulated outcomes under limited computational budget and long runtime, even for one simulation replication. Methods We developed a two-phase recalibration procedure. As a proof-of-the-concept study, we verified the procedure in the context of sex-specific colorectal neoplasia development. We considered two individual-based state-transition stochastic simulation models, estimating model parameters that govern colorectal adenoma occurrence and its growth through three preclinical states: non-advanced precancerous polyp, advanced precancerous polyp, and cancerous polyp. For the calibration, we used a weighted-sum-squared error between three prevalence values reported in the literature and the corresponding simulation outcomes. In phase 1 of the calibration procedure, we first extracted the baseline parameter design from relevant studies on the same model. We then performed sampling-based searches within a proper range around the baseline design to identify the initial set of good candidate designs. In phase 2, we performed local search (e.g., the Nelder-Mead algorithm), starting from the candidate designs identified at the end of phase 1. Further, we investigated the efficiency of exploring dimensions of the parameter space sequentially based on our prior knowledge of the system dynamics. Results The efficiency of our two-phase re-calibration procedure was first investigated with CMOST, a relatively inexpensive computational model. It was then further verified with the V/NCS model, which is much more expensive. Overall, our two-phase procedure showed a better goodness-of-fit than the straightforward employment of the Nelder-Mead algorithm, when only a limited number of simulation replications were allowed. In addition, in phase 2, performing local search along parameter space dimensions sequentially was more efficient than performing the search over all dimensions concurrently. Conclusion The proposed two-phase re-calibration procedure is efficient at estimating parameters of computationally expensive stochastic dynamic disease models.

Nurse-administered propofol sedation was restricted to anesthesiologists in 2009, a practice that has contributed to spiraling health care costs in the United States.The aim of this study was to evaluate the safety of endoscopist-directed balanced propofol sedation (EDBPS).We identified patients undergoing endoscopy with EDBPS from January 1, 2017, to June 20, 2017, and abstracted their medical records. Adverse events (AEs) included: hypoxia (oxygen saturation 90%); hypotension [(a) systolic blood pressure 90 mm Hg, (b) systolic blood pressure decline of50 mm Hg, (c) decline in mean arterial pressure of30%]; bradycardia (heart rate of 40 beats/min). Logistic regression identified factors independently associated with AEs.A total of 1897 patients received EDBPS during the study period [mean age: 55 y (SD=11.4 y); 56.4% women]. Patients received median doses of 50 µg fentanyl, 2 mg of midazolam, and a mean propofol dose of 160±99 mg. There were no major complications (upper 95% confidence interval, 0.19%). Overall, 334 patients (17.6%) experienced a clinically insignificant AE: 65 (3.4%) experienced transient hypoxia, 277 patients (14.6%) experienced hypotension, 2 had transient bradycardia. In bivariate analysis, older age was associated with risk for hypotension, propofol dose was associated with transient hypoxemia, and procedure duration was associated with both hypotension and transient hypoxia. In multivariate analysis, only procedure length was associated with AEs (odds ratio scale 10; odds ratio=1.07; 95% confidence interval, 1.05-1.09, P0.001).EDBPS is safe for endoscopic sedation. Given the higher cost of anesthesia-administered propofol, endoscopists should reinstate EDBPS by revising institutional sedation policies.

Background & Aims Incidence and mortality associated with early-age onset colorectal cancer (EAO-CRC) is increasing, prompting professional society recommendations to lower the screening age in average-risk individuals. The yield of screening individuals younger than 50 years is not known. Methods A systematic review of 3 databases from inception through July 2020 was performed in all languages that reported colonoscopy findings in average-risk individuals younger than 50 years. The primary outcomes were EAO colorectal neoplasia (CRN) and advanced colorectal neoplasia (aCRN) prevalence. Subgroup analyses were performed based on sex, geographic location, time period, and age, including comparison with those aged 50–59 years. Generalized linear mixed model with random intercept logistic regression and fixed subgroup effects were performed. Results Of 10,123 unique articles, 17 studies published between 2002 and 2020, including 51,811 average-risk individuals from 4 continents, were included. The pooled rate of EAO-CRN was 13.7% (95% confidence interval [CI], 0.112%–0.168%) and EAO-aCRN was 2.2% (95% CI, 0.016%–0.031%). Prevalence of CRC was 0.05% (95% CI, 0.00029%–0.0008%). Rates of EAO-CRN were higher in men compared with women (relative risk, 1.71%; 95% CI, 1.49%–1.98%), and highest in the United States (15.6%; 95% CI, 12.2%–19.7%) compared with Europe (14.9%; 95% CI, 6.9%–29.3%), East Asia (13.4%; 95% CI, 10.3%–17.2%), and the Middle East (9.8%; 95% CI, 7.8%–12.2%) (P = .04) The rate of EAO-CRN in age groups 45–49 years and 50–59 years was 17.8% (95% CI, 14.5%–21.6%) and 24.8% (95% CI, 19.5%–30.8%), respectively (P = .04). The rate of EAO-aCRN in age group 45–49 years was 3.6% (95% CI, 1.9%–6.7%) and 4.2% (95% CI, 3.2%–5.7%), respectively (P = .69). Conclusions The rate of aCRN in individuals aged 45–49 years was similar to the rate observed in individual aged 50–59 years, suggesting that expanding screening to this population could yield a similar impact on colorectal cancer risk reduction.

Background. Developing efficient procedures of model calibration, which entails matching model predictions to observed outcomes, has gained increasing attention. With faithful but complex simulation models established for cancer diseases, key parameters of cancer natural history can be investigated for possible fits, which can subsequently inform optimal prevention and treatment strategies. When multiple calibration targets exist, one approach to identifying optimal parameters relies on the Pareto frontier. However, computational burdens associated with higher-dimensional parameter spaces require a metamodeling approach. The goal of this work is to explore multiobjective calibration using Gaussian process regression (GPR) with an eye toward how multiple goodness-of-fit (GOF) criteria identify Pareto-optimal parameters. Methods. We applied GPR, a metamodeling technique, to estimate colorectal cancer (CRC)–related prevalence rates simulated from a microsimulation model of CRC natural history, known as the Colon Modeling Open Source Tool (CMOST). We embedded GPR metamodels within a Pareto optimization framework to identify best-fitting parameters for age-, adenoma-, and adenoma staging–dependent transition probabilities and risk factors. The Pareto frontier approach is demonstrated using genetic algorithms with both sum-of-squared errors (SSEs) and Poisson deviance GOF criteria. Results. The GPR metamodel is able to approximate CMOST outputs accurately on 2 separate parameter sets. Both GOF criteria are able to identify different best-fitting parameter sets on the Pareto frontier. The SSE criterion emphasizes the importance of age-specific adenoma progression parameters, while the Poisson criterion prioritizes adenoma-specific progression parameters. Conclusion. Different GOF criteria assert different components of the CRC natural history. The combination of multiobjective optimization and nonparametric regression, along with diverse GOF criteria, can advance the calibration process by identifying optimal regions of the underlying parameter landscape.

Objectives Brain tumors, including pituitary adenomas (PA), cause anxiety and distress, with a high unmet need for information correlating with increased anxiety. Condition-specific education may alleviate anxiety. We explored patients’ experience around the diagnosis of a PA and piloted a patient education intervention to address peridiagnostic anxiety in adults diagnosed with PA. Methods Anxiety, patient satisfaction, patient knowledge, and need for information were measured prior to, immediately after, and 1 month following the appointment in this multimethods study. A phone interview to explore patient diagnostic and intervention experiences was analyzed using qualitative methods. Results A total of 17 patients participated in the study; 15 completed the interview. The baseline need for information was high. Disease-specific anxiety decreased, and patient knowledge and satisfaction increased significantly after the initial visit. Interview analysis identified 3 main themes: (1) the importance of communication; (2) the need for information; and (3) the impact of the diagnosis on patient experience. Conclusions For patients with newly diagnosed PA, the diagnostic experience was associated with high levels of anxiety. Patients expressed a need for information. Information delivery reduced anxiety and had a positive impact on patient satisfaction. Practice Implications The study findings suggest a need for a streamlined diagnostic process with readily accessible information.

BACKGROUND AND AIMS Until recently, guidelines recommended a 3-year surveillance colonoscopy for persons with 3 to 10 nonadvanced adenomas (NAA). In this study, we quantify yield for metachronous advanced neoplasia (AN); attempt to identify risk factors for AN; and measure colorectal cancer (CRC) incidence and mortality. METHODS We used natural language processing to screen an existing data set for Veterans with 3 to 10 NAA. We manually reviewed colonoscopy and pathology reports to verify baseline findings and determine results of subsequent colonoscopy (sCY). Baseline features were extracted from the electronic medical record (EMR) and a national data set, CRC incidence was obtained from the Veterans Affairs cancer registry, and CRC mortality from the National Death Index through September 30, 2017. CRC incidence and mortality were compared between Veterans who did versus did not have sCY. RESULTS Natural language processing identified 3673 Veterans who potentially had 3 to 10 NAA, of which 1672 were excluded after EMR review. In the analytical cohort of 2001 subjects, 1178 (59%) had sCY at a mean (SD) follow-up of 4.3 (2.2) years. The sCY group was younger (mean age: 61 vs. 67 y; P

Fecal immunochemical testing (FIT) is widely used for colorectal cancer screening, its only indication. Its effect on clinical decision-making beyond screening is unknown. We studied the use of FIT in emergency and inpatient settings and its impact on patient care.Using electronic medical records, we reviewed all non-ambulatory FITs performed from November 2017 to October 2019 at a tertiary care community hospital. We collected data on demographics, indications, gastroenterology consultations, and endoscopic procedures. Multivariate logistic regression was performed to determine the effect of FIT on gastroenterology consultation and endoscopy.We identified 550 patients with at least 1 FIT test. Only 3 FITs (0.5%) were performed for colorectal cancer screening. FITs were primarily ordered from the emergency department (45.3%) or inpatient hospital floor (42.2%). Anemia (44.0%), followed by gastrointestinal bleeding (40.9%), were the most common indications. FIT was positive in 253 patients (46.0%), and gastroenterology consultation was obtained for 47.4% (n = 120), compared with 14.5% (n = 43) of the 297 FIT-negative patients (odds ratio 3.28; 95% confidence interval, 2.23-4.82, P.0001). A potential bleeding source was identified in 80% of patients with reported or witnessed overt gastrointestinal bleeding, a similar proportion (80.7%; P = .92) to patients who were FIT positive with overt gastrointestinal bleeding. Multivariate analysis showed that melena, hematemesis, and a positive FIT were associated with gastroenterology consultation (all P.05), while only melena (odds ratio 3.34; 95% confidence interval, 1.48-7.54) was associated with endoscopy.Nearly all emergency department and inpatient FIT use was inappropriate. FIT resulted in more gastroenterology consultation but was not independently associated with inpatient endoscopy.

Background: Although colonoscopy (CY) may be considered the best screening test for colorectal cancer (CRC), annual fecal immunochemical test (FIT), which quantifies fecal hemoglobin is a viable alternative. Countries and healthcare systems using FIT-based screening may need to prioritize which FIT positive persons requires CY sooner (e.g. within the same fiscal year). We conducted a systematic review of published literature to understand how the yield/positive predictive value (PPV) of FIT could be improved. Study Design: We performed a search of electronic databases for articles published between 2015 and June 2020. Titles, abstracts, and full texts were independently screened. Included studies fulfilled predetermined criteria and had descriptive and quantitative data extracted. We identified studies comparing the yield of FIT for advanced colorectal neoplasia ([AN], CRC plus advanced adenomas) among FIT positive persons to the yield of AN when FIT is combined with risk factors (age, sex, BMI, etc.). Data were extracted to find yield and efficiency of FIT alone vs FIT plus risk factors among FIT positive persons. Results: From 623 titles reviewed, 4 studies met inclusion criteria. The objective of the studies was to increase the yield of AN or CRC in FIT positive patients. The number needed to scope (NNS) among FIT positives to detect AN significantly decreased for each study when looking at high risk groups as yield/PPV increased. The yield with FIT alone ranged from 24% to 46% and the NNS from 2.2 to 4.1. With risk factors, yield and NNS among those at high risk were 33.2 % to 75.6% and from 1.3 to 3.0, respectively. Conclusion and Potential Impact: This systematic review quantifies how risk factors improve the yield for AN in FIT positive persons, which is information required for countries and health care settings with limited resources that need to direct CY resources to FIT positive patients at high risk for AN.