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Browsing by Subject "Colonoscopy"

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    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
    (American Medical Association, 2023-07-03) Robertson, Douglas J.; Dominitz, Jason A.; Beed, Alexander; Boardman, Kathy D.; Del Curto, Barbara J.; Guarino, Peter D.; Imperiale, Thomas F.; LaCasse, Andrew; Larson, Meaghan F.; Gupta, Samir; Lieberman, David; Planeta, Beata; Shaukat, Aasma; Sultan, Shanaz; Menees, Stacy B.; Saini, Sameer D.; Schoenfeld, Philip; Goebel, Stephan; von Rosenvinge, Erik C.; Baffy, Gyorgy; Halasz, Ildiko; Pedrosa, Marcos C.; Kahng, Lyn Sue; Cassim, Riaz; Greer, Katarina B.; Kinnard, Margaret F.; Bhatt, Divya B.; Dunbar, Kerry B.; Harford, William V.; Mengshol, John A.; Olson, Jed E.; Patel, Swati G.; Antaki, Fadi; Fisher, Deborah A.; Sullivan, Brian A.; Lenza, Christopher; Prajapati, Devang N.; Wong, Helen; Beyth, Rebecca; Lieb, John G.; Manlolo, Joseph; Ona, Fernando V.; Cole, Rhonda A.; Khalaf, Natalia; Kahi, Charles J.; Kohli, Divyanshoo Rai; Rai, Tarun; Sharma, Prateek; Anastasiou, Jiannis; Hagedorn, Curt; Fernando, Ronald S.; Jackson, Christian S.; Jamal, M. Mazen; Lee, Robert H.; Merchant, Farrukh; May, Folasade P.; Pisegna, Joseph R.; Omer, Endashaw; Parajuli, Dipendra; Said, Adnan; Nguyen, Toan D.; Tombazzi, Claudio Ruben; Feldman, Paul A.; Jacob, Leslie; Koppelman, Rachel N.; Lehenbauer, Kyle P.; Desai, Deepak S.; Madhoun, Mohammad F.; Tierney, William M.; Ho, Minh Q.; Hockman, Heather J.; Lopez, Christopher; Carter Paulson, Emily; Tobi, Martin; Pinillos, Hugo L.; Young, Michele; Ho, Nancy C.; Mascarenhas, Ranjan; Promrat, Kirrichai; Mutha, Pritesh R.; Pandak, William M.; Shah, Tilak; Schubert, Mitchell; Pancotto, Frank S.; Gawron, Andrew J.; Underwood, Amelia E.; Ho, Samuel B.; Magno-Pagatzaurtundua, Priscilla; Toro, Doris H.; Beymer, Charles H.; Kaz, Andrew M.; Elwing, Jill; Gill, Jeffrey A.; Goldsmith, Susan F.; Yao, Michael D.; Protiva, Petr; Pohl, Heiko; Kyriakides, Tassos; CONFIRM Study Group; Medicine, School of Medicine
    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.
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    Benefits and challenges in implementation of artificial intelligence in colonoscopy: World Endoscopy Organization position statement
    (Wiley, 2023) Mori, Yuichi; East, James E.; Hassan, Cesare; Halvorsen, Natalie; Berzin, Tyler M.; Byrne, Michael; von Renteln, Daniel; Hewett, David G.; Repici, Alessandro; Ramchandani, Mohan; Al Khatry, Maryam; Kudo, Shin-ei; Wang, Pu; Yu, Honggang; Saito, Yutaka; Misawa, Masashi; Parasa, Sravanthi; Ogawa Matsubayashi, Carolina; Ogata, Haruhiko; Tajiri, Hisao; Pausawasdi, Nonthalee; Dekker, Evelien; Ahmad, Omer F.; Sharma, Prateek; Rex, Douglas K.; Medicine, School of Medicine
    The number of artificial intelligence (AI) tools for colonoscopy on the market is increasing with supporting clinical evidence. Nevertheless, their implementation is not going smoothly for a variety of reasons, including lack of data on clinical benefits and cost-effectiveness, lack of trustworthy guidelines, uncertain indications, and cost for implementation. To address this issue and better guide practitioners, the World Endoscopy Organization (WEO) has provided its perspective about the status of AI in colonoscopy as the position statement. WEO Position Statement: Statement 1.1: Computer-aided detection (CADe) for colorectal polyps is likely to improve colonoscopy effectiveness by reducing adenoma miss rates and thus increase adenoma detection; Statement 1.2: In the short term, use of CADe is likely to increase health-care costs by detecting more adenomas; Statement 1.3: In the long term, the increased cost by CADe could be balanced by savings in costs related to cancer treatment (surgery, chemotherapy, palliative care) due to CADe-related cancer prevention; Statement 1.4: Health-care delivery systems and authorities should evaluate the cost-effectiveness of CADe to support its use in clinical practice; Statement 2.1: Computer-aided diagnosis (CADx) for diminutive polyps (≤5 mm), when it has sufficient accuracy, is expected to reduce health-care costs by reducing polypectomies, pathological examinations, or both; Statement 2.2: Health-care delivery systems and authorities should evaluate the cost-effectiveness of CADx to support its use in clinical practice; Statement 3: We recommend that a broad range of high-quality cost-effectiveness research should be undertaken to understand whether AI implementation benefits populations and societies in different health-care systems.
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    Clip Closure Prevents Bleeding After Endoscopic Resection of Large Colon Polyps in a Randomized Trial
    (Elsevier, 2019-10) Pohl, Heiko; Grimm, Ian S.; Moyer, Matthew T.; Hasan, Muhammad K.; Pleskow, Douglas; Elmunzer, B. Joseph; Khashab, Mouen A.; Sanaei, Omid; Al-Kawas, Firas H.; Gordon, Stuart R.; Mathew, Abraham; Levenick, John M.; Aslanian, Harry R.; Antaki, Fadi; von Renteln, Daniel; Crockett, Seth D.; Rastogi, Amit; Gill, Jeffrey A.; Law, Ryan J.; Elias, Pooja A.; Pellise, Maria; Wallace, Michael B.; Mackenzie, Todd A.; Rex, Douglas K.; Medicine, School of Medicine
    Background & aims: Bleeding is the most common severe complication after endoscopic mucosal resection of large colon polyps and is associated with significant morbidity and cost. We examined whether prophylactic closure of the mucosal defect with hemoclips after polyp resection reduces the risk of bleeding. Methods: We performed a multicenter, randomized trial of patients with a large nonpedunculated colon polyp (≥20 mm) at 18 medical centers in North America and Spain from April 2013 through October 2017. Patients were randomly assigned to groups that underwent endoscopic closure with a clip (clip group) or no closure (control group) and followed. The primary outcome, postprocedure bleeding, was defined as a severe bleeding event that required hospitalization, a blood transfusion, colonoscopy, surgery, or another invasive intervention within 30 days after completion of the colonoscopy. Subgroup analyses included postprocedure bleeding with polyp location, polyp size, or use of periprocedural antithrombotic medications. We also examined the risk of any serious adverse event. Results: A total of 919 patients were randomly assigned to groups and completed follow-up. Postprocedure bleeding occurred in 3.5% of patients in the clip group and 7.1% in the control group (absolute risk difference [ARD] 3.6%; 95% confidence interval [CI] 0.7%-6.5%). Among 615 patients (66.9%) with a proximal large polyp, the risk of bleeding in the clip group was 3.3% and in the control group was 9.6% (ARD 6.3%; 95% CI 2.5%-10.1%); among patients with a distal large polyp, the risks were 4.0% in the clip group and 1.4% in the control group (ARD -2.6%; 95% CI -6.3% to -1.1%). The effect of clip closure was independent of antithrombotic medications or polyp size. Serious adverse events occurred in 4.8% of patients in the clip group and 9.5% of patients in the control group (ARD 4.6%; 95% CI 1.3%-8.0%). Conclusions: In a randomized trial, we found that endoscopic clip closure of the mucosal defect following resection of large colon polyps reduces risk of postprocedure bleeding. The protective effect appeared to be restricted to large polyps located in the proximal colon.
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    Colorectal Cancer Screening Programs in Latin America: A Systematic Review and Meta-Analysis
    (American Medical Association, 2024-02-05) Montalvan-Sanchez, Eleazar E.; Norwood, Dalton A.; Dougherty, Michael; Beas, Renato; Guranizo-Ortiz, Maria; Ramirez-Rojas, Miriam; Morgan, Douglas R.; Imperiale, Thomas F.; Medicine, School of Medicine
    Importance: Colorectal cancer (CRC) is a leading cause of cancer-related mortality globally, with increasing incidence and mortality in Latin America. CRC screening programs can reduce disease burden, but information on screening programs in Latin America is limited. Objective: To describe characteristics (eg, type of program, uptake, neoplastic yield) of CRC screening programs in Latin America. Data sources: PubMed, Ovid MEDLINE, EMBASE, Cochrane, PsycINFO, Web of Science Core Collection, LILACS, and SciELO were searched from inception to February 2023. Relevant references from bibliographies, conference proceedings, and gray literature were considered. The search strategy included English, Spanish, and Portuguese terms. Study selection: Included were studies of CRC screening programs in Latin America using fecal immunochemical test (FIT) or colonoscopy as the primary screening method. Four reviewers independently assessed study eligibility based on titles, with review of abstracts and full texts as needed. Data extraction and synthesis: Guidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were followed for data abstraction and quality assessment. Descriptive information was extracted, and data were pooled using a random-effects model. Main outcomes and measures: Program performance indicators included rates of participation and FIT positivity, adenoma detection rate (ADR), advanced adenoma detection rate (AADR), CRC detection rate, and colonoscopy quality indicators. Results: There were 17 studies included from upper middle-income and high-income countries in Latin America with a total of 123 929 participants. Thirteen studies used FIT as the initial screening method, whereas 4 used screening colonoscopy. The participation rate in FIT-based programs was 85.8% (95% CI, 78.5%-91.4%). FIT positivity rates were 15.2% (95% CI, 9.6%-21.8%) for the 50-ng/mL threshold and 9.7% (95% CI, 6.8%-13.0%) for the 100-ng/mL threshold. For FIT-based studies, the pooled ADR was 39.0% (95% CI, 29.3%-49.2%) and CRC detection rate was 4.9% (95% CI, 2.6%-7.9%); for screening colonoscopy-based studies, the pooled ADR was 19.9% (95% CI, 15.5%-24.8%) and CRC detection rate was 0.4% (95% CI, 0.1%-0.8%). Conclusions and relevance: This systematic review and meta-analysis suggests that CRC screening in upper middle-income countries in Latin America is feasible, detecting rates of neoplasia comparable with those of high-income regions. Population-based screening programs should be developed or enhanced in these settings. There is a knowledge gap regarding feasibility and yield of screening programs in lower middle-income countries.
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    Combination of Mucosa-Exposure Device and Computer-Aided Detection for Adenoma Detection During Colonoscopy: A Randomized Trial
    (Elsevier, 2023-07) Spadaccini, Marco; Hassan, Cesare; Rondonotti, Emanuele; Antonelli, Giulio; Andrisani, Gianluca; Lollo, Gianluca; Auriemma, Francesco; Iacopini, Federico; Facciorusso, Antonio; Maselli, Roberta; Fugazza, Alessandro; Bambina Bergna, Irene Maria; Cereatti, Fabrizio; Mangiavillano, Benedetto; Radaelli, Franco; Di Matteo, Francesco; Gross, Seth A.; Sharma, Prateek; Mori, Yuichi; Bretthauer, Michael; Rex, Douglas K.; Repici, Alessandro; Medicine, School of Medicine
    Background & Aims Both computer-aided detection (CADe)-assisted and Endocuff-assisted colonoscopy have been found to increase adenoma detection. We investigated the performance of the combination of the 2 tools compared with CADe-assisted colonoscopy alone to detect colorectal neoplasias during colonoscopy in a multicenter randomized trial. Methods Men and women undergoing colonoscopy for colorectal cancer screening, polyp surveillance, or clincial indications at 6 centers in Italy and Switzerland were enrolled. Patients were assigned (1:1) to colonoscopy with the combinations of CADe (GI-Genius; Medtronic) and a mucosal exposure device (Endocuff Vision [ECV]; Olympus) or to CADe-assisted colonoscopy alone (control group). All detected lesions were removed and sent to histopathology for diagnosis. The primary outcome was adenoma detection rate (percentage of patients with at least 1 histologically proven adenoma or carcinoma). Secondary outcomes were adenomas detected per colonoscopy, advanced adenomas and serrated lesions detection rate, the rate of unnecessary polypectomies (polyp resection without histologically proven adenomas), and withdrawal time. Results From July 1, 2021 to May 31, 2022, there were 1316 subjects randomized and eligible for analysis; 660 to the ECV group, 656 to the control group). The adenoma detection rate was significantly higher in the ECV group (49.6%) than in the control group (44.0%) (relative risk, 1.12; 95% CI, 1.00–1.26; P = .04). Adenomas detected per colonoscopy were significantly higher in the ECV group (mean ± SD, 0.94 ± 0.54) than in the control group (0.74 ± 0.21) (incidence rate ratio, 1.26; 95% CI, 1.04–1.54; P = .02). The 2 groups did not differ in term of detection of advanced adenomas and serrated lesions. There was no significant difference between groups in mean ± SD withdrawal time (9.01 ± 2.48 seconds for the ECV group vs 8.96 ± 2.24 seconds for controls; P = .69) or proportion of subjects undergoing unnecessary polypectomies (relative risk, 0.89; 95% CI, 0.69–1.14; P = .38). Conclusions The combination of CADe and ECV during colonoscopy increases adenoma detection rate and adenomas detected per colonoscopy without increasing withdrawal time compared with CADe alone.
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    Computer-aided detection for colorectal neoplasia in randomized and non-randomized studies
    (Thieme, 2024-04-23) Mori, Yuichi; Patel, Harsh K.; Repici, Alessandro; Rex, Douglas K.; Sharma, Prateek; Hassan, Cesare; Medicine, School of Medicine
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    Contribution of patient, physician, and environmental factors to demographic and health variation in colonoscopy follow-up for abnormal colorectal cancer screening test results
    (Wiley, 2017-09-15) Partin, Melissa R.; Gravely, Amy; Burgess, James F., Jr.; Haggstrom, David; Lillie, Sarah E.; Nelson, David B.; Nugent, Sean; Shaukat, Aasma; Sultan, Shahnaz; Walter, Louise C.; Burgess, Diana J.; Medicine, School of Medicine
    BACKGROUND: Patient, physician, and environmental factors were identified, and the authors examined the contribution of these factors to demographic and health variation in colonoscopy follow-up after a positive fecal occult blood test/fecal immunochemical test (FOBT/FIT) screening. METHODS: In total, 76,243 FOBT/FIT-positive patients were identified from 120 Veterans Health Administration (VHA) facilities between August 16, 2009 and March 20, 2011 and were followed for 6 months. Patient demographic (race/ethnicity, sex, age, marital status) and health characteristics (comorbidities), physician characteristics (training level, whether primary care provider) and behaviors (inappropriate FOBT/FIT screening), and environmental factors (geographic access, facility type) were identified from VHA administrative records. Patient behaviors (refusal, private sector colonoscopy use) were estimated with statistical text mining conducted on clinic notes, and follow-up predictors and adjusted rates were estimated using hierarchical logistic regression. RESULTS: Roughly 50% of individuals completed a colonoscopy at a VHA facility within 6 months. Age and comorbidity score were negatively associated with follow-up. Blacks were more likely to receive follow-up than whites. Environmental factors attenuated but did not fully account for these differences. Patient behaviors (refusal, private sector colonoscopy use) and physician behaviors (inappropriate screening) fully accounted for the small reverse race disparity and attenuated variation by age and comorbidity score. Patient behaviors (refusal and private sector colonoscopy use) contributed more to variation in follow-up rates than physician behaviors (inappropriate screening). CONCLUSIONS: In the VHA, blacks are more likely to receive colonoscopy follow-up for positive FOBT/FIT results than whites, and follow-up rates markedly decline with advancing age and comorbidity burden. Patient and physician behaviors explain race variation in follow-up rates and contribute to variation by age and comorbidity burden. Cancer 2017;123:3502-12. Published 2017. This article is a US Government work and is in the public domain in the USA.
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    Cost-effectiveness of artificial intelligence for screening colonoscopy: a modelling study
    (Elsevier, 2022) Areia, Miguel; Mori, Yuichi; Correale, Loredana; Repici, Alessandro; Bretthauer, Michael; Sharma, Prateek; Taveira, Filipe; Spadaccini, Marco; Antonelli, Giulio; Ebigbo, Alanna; Kudo, Shin-ei; Arribas, Julia; Barua, Ishita; Kaminski, Michal F.; Messmann, Helmut; Rex, Douglas K.; Dinis-Ribeiro, Mário; Hassan, Cesare; Medicine, School of Medicine
    Background: Artificial intelligence (AI) tools increase detection of precancerous polyps during colonoscopy and might contribute to long-term colorectal cancer prevention. The aim of the study was to investigate the incremental effect of the implementation of AI detection tools in screening colonoscopy on colorectal cancer incidence and mortality, and the cost-effectiveness of such tools. Methods: We conducted Markov model microsimulation of using colonoscopy with and without AI for colorectal cancer screening for individuals at average risk (no personal or family history of colorectal cancer, adenomas, inflammatory bowel disease, or hereditary colorectal cancer syndrome). We ran the microsimulation in a hypothetical cohort of 100 000 individuals in the USA aged 50-100 years. The primary analysis investigated screening colonoscopy with versus without AI every 10 years starting at age 50 years and finishing at age 80 years, with follow-up until age 100 years, assuming 60% screening population uptake. In secondary analyses, we modelled once-in-life screening colonoscopy at age 65 years in adults aged 50-79 years at average risk for colorectal cancer. Post-polypectomy surveillance followed the simplified current guideline. Costs of AI tools and cost for downstream treatment of screening detected disease were estimated with 3% annual discount rates. The main outcome measures included the incremental effect of AI-assisted colonoscopy versus standard (no-AI) colonoscopy on colorectal cancer incidence and mortality, and cost-effectiveness of screening projected for the average risk screening US population. Findings: In the primary analyses, compared with no screening, the relative reduction of colorectal cancer incidence with screening colonoscopy without AI tools was 44·2% and with screening colonoscopy with AI tools was 48·9% (4·8% incremental gain). Compared with no screening, the relative reduction in colorectal cancer mortality with screening colonoscopy with no AI was 48·7% and with screening colonoscopy with AI was 52·3% (3·6% incremental gain). AI detection tools decreased the discounted costs per screened individual from $3400 to $3343 (a saving of $57 per individual). Results were similar in the secondary analyses modelling once-in-life colonoscopy. At the US population level, the implementation of AI detection during screening colonoscopy resulted in yearly additional prevention of 7194 colorectal cancer cases and 2089 related deaths, and a yearly saving of US$290 million. Interpretation: Our findings suggest that implementation of AI detection tools in screening colonoscopy is a cost-saving strategy to further prevent colorectal cancer incidence and mortality.
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    Delayed Removal of Entrapped Snare in Colonoscopic Polypectomy
    (Wolters Kluwer, 2021-01-27) Phatharacharukul, Parkpoom; Wajid, Maryiam; Fatima, Hala; Medicine, School of Medicine
    Snare entrapment is a rare complication of hot snare polypectomy of large colon polyps. We report a case of snare entrapment in our unit and its management. This report highlights the method of delayed removal of snare followed by repeat colonoscopy.
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    Derivation and Validation of a Scoring System to Stratify Risk for Advanced Colorectal Neoplasia in Asymptomatic Adults: A Cross-sectional Study
    (American College of Physicians, 2015-09-01) Imperiale, Thomas F.; Monahan, Patrick O.; Stump, Timothy E.; Glowinski, Elizabeth A.; Ransohoff, David F.; Department of Medicine, IU School of Medicine
    BACKGROUND: Several methods are recommended equally strongly for colorectal cancer screening in average-risk persons. Risk stratification would enable tailoring of screening within this group, with less invasive tests (sigmoidoscopy or occult blood tests) for lower-risk persons and colonoscopy for higher-risk persons. OBJECTIVE: To create a risk index for advanced neoplasia (colorectal cancer and adenomas or serrated polyps ≥1.0 cm, villous histology, or high-grade dysplasia) anywhere in the colorectum, using the most common risk factors for colorectal neoplasia. DESIGN: Cross-sectional study. SETTING: Multiple endoscopy units, primarily in the Midwest. PATIENTS: Persons aged 50 to 80 years undergoing initial screening colonoscopy (December 2004 to September 2011). MEASUREMENTS: Derivation and validation of a risk index based on points from regression coefficients for age, sex, waist circumference, cigarette smoking, and family history of colorectal cancer. RESULTS: Among 2993 persons in the derivation set, prevalence of advanced neoplasia was 9.4%. Risks for advanced neoplasia in persons at very low, low, intermediate, and high risk were 1.92% (95% CI, 0.63% to 4.43%), 4.88% (CI, 3.79% to 6.18%), 9.93% (CI, 8.09% to 12.0%), and 24.9% (CI, 21.1% to 29.1%), respectively (P < 0.001). Sigmoidoscopy to the descending colon in the low-risk groups would have detected 51 of 70 (73% [CI, 61% to 83%]) advanced neoplasms. Among 1467 persons in the validation set, corresponding risks for advanced neoplasia were 1.65% (CI, 0.20% to 5.84%), 3.31% (CI, 2.08% to 4.97%), 10.9% (CI, 8.26% to 14.1%), and 22.3% (CI, 16.9% to 28.5%), respectively (P < 0.001). Sigmoidoscopy would have detected 21 of 24 (87.5% [CI, 68% to 97%]) advanced neoplasms. LIMITATIONS: Split-sample validation; results apply to first-time screening. CONCLUSION: This index stratifies risk for advanced neoplasia among average-risk persons by identifying lower-risk groups for which noncolonoscopy strategies may be effective and efficient and a higher-risk group for which colonoscopy may be preferred. PRIMARY FUNDING SOURCE: National Cancer Institute, Walther Cancer Institute, Indiana University Simon Cancer Center, and Indiana Clinical and Translational Sciences Institute.
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