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Background: Colorectal cancer (CRC) incidence at ages <50 years is increasing worldwide. Screening initiation was lowered to 45 years in the United States. The cost‐effectiveness of initiating CRC screening at 45 years in Israel was assessed with the aim of informing national policy and addressing internationally relevant questions. Methods: A validated CRC screening model was calibrated to Israeli data and examined annual fecal immunochemical testing (FIT) or colonoscopy every 10 years from 45 to 74 years (FIT45‐74 or Colo45‐74) versus from 50 to 74 years (FIT50‐74 or Colo50‐74). The addition of a fourth colonoscopy at 75 years was explored, subanalyses were performed by sex/ethnicity, and resource demands were estimated. Results: FIT50‐74 and Colo50‐74 reduced CRC incidence by 57% and 70% and mortality by 70% and 77%, respectively, versus no screening, with greater absolute impact in Jews/Other versus Arabs but comparable relative impact. FIT45‐74 further reduced CRC incidence and mortality by an absolute 3% and 2%, respectively. With Colo45‐74 versus Colo50‐74, CRC cases and deaths increased slightly as three colonoscopies per lifetime shifted to 5 years earlier but mean quality‐adjusted life‐years gained (QALYGs) per person increased. FIT45‐74 and Colo45‐74 cost 23,800–53,900 new Israeli shekels (NIS)/QALYG and 110,600–162,700 NIS/QALYG, with the lowest and highest values among Jewish/Other men and Arab women, respectively. A fourth lifetime colonoscopy cost 48,700 NIS/QALYG. Lowering FIT initiation to 45 years with modest participation required 19,300 additional colonoscopies in the first 3 years. Conclusions: Beginning CRC screening at 45 years in Israel is projected to yield modest clinical benefits at acceptable costs per QALYG. Despite different estimates by sex/ethnicity, a uniform national policy is favored. These findings can inform Israeli guidelines and serve as a case study internationally. In a modeling study of colorectal cancer (CRC) screening in Israel, where CRC incidence at ages <50 years has not increased, lowering CRC screening initiation to 45 years yielded moderate clinical benefits at acceptable costs. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The rates of serious cardiac, neurologic, and pulmonary events attributable to colonoscopy are poorly characterized, and background event rates are usually not accounted for. METHODS: We performed a multistate population-based study using changepoint analysis to determine the rates and timing of serious gastrointestinal and nongastrointestinal adverse events associated with screening/surveillance colonoscopy, including analyses by age (45 to <55, 55 to <65, 65 to <75, and ≥75 years). Among 4.5 million persons in the Ambulatory Surgery and Services Databases of California, Florida, and New York who underwent screening/surveillance colonoscopy in 2005-2015, we ascertained serious postcolonoscopy events in excess of background rates in Emergency Department (SEDD) and Inpatient Databases (SID). RESULTS: Most serious nongastrointestinal postcolonoscopy events were expected based on the background rate and not associatedwith colonoscopy itself. However, associated nongastrointestinal events predominated over gastrointestinal events at ages ≥65 years, including more myocardial infarctions plus ischemic strokes than perforations at ages ≥75 years (361 [95% confidence intervals {CI} 312-419] plus 1,279 [95% CI 1,182-1,384] vs 912 [95% CI 831-1,002] per million). At all ages, the observed-to-expected ratios for days 0-7, 0-30, and 0-60 after colonoscopy were substantially >1 for gastrointestinal bleeding and perforation, but minimally >1 for most nongastrointestinal complications. Risk periods ranged from 1 to 125 days depending on complication type and age. No excess postcolonoscopy in-hospital deaths were observed. DISCUSSION: Although crude counts substantially overestimate nongastrointestinal events associated with colonoscopy, nongastrointestinal complications exceed bleeding and perforation risk in older persons. The inability to ascertain modifications to antiplatelet therapy was a study limitation. Our results can inform benefit-to-risk determinations for preventive colonoscopy. [ABSTRACT FROM AUTHOR]

Background and Aims: Ensemble machine-learning methods, like the superlearner, combine multiple models into a single one to enhance predictive accuracy. Here we explore the potential of the superlearner as a benchmarking tool for clinical risk prediction, illustrating the approach to identifying significant liver fibrosis among patients with NAFLD., Approach and Results: We used 23 demographic/clinical variables to train superlearner(s) on data from the NASH-clinical research network observational study (n = 648) and validated models with data from the FLINT trial (n = 270) and National Health and Nutrition Examination Survey (NHANES) participants with NAFLD (n = 1244). Comparing the superlearner's performance to existing models (Fibrosis-4 [FIB-4], NAFLD fibrosis score, Forns, AST to Platelet Ratio Index [APRI], BARD, and Steatosis-Associated Fibrosis Estimator [SAFE]), it exhibited strong discriminative ability in the FLINT and NHANES validation sets, with AUCs of 0.79 (95% CI: 0.73-0.84) and 0.74 (95% CI: 0.68-0.79) respectively., Conclusions: Notably, the SAFE score performed similarly to the superlearner, both of which outperformed FIB-4, APRI, Forns, and BARD scores in the validation data sets. Surprisingly, the superlearner derived from 12 base models matched the performance of one with 90 base models. Overall, the superlearner, being the "best-in-class" machine-learning predictor, excelled in detecting fibrotic NASH, and this approach can be used to benchmark the performance of conventional clinical risk prediction models., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background and Aims: Since the implementation of the model for end-stage liver disease (MELD) score to determine waitlist priority for liver transplant (LT) in 2002, the score has been capped at 40. Recently, the MELD 3.0 score was proposed to improve upon MELD-Na. Here, we examine waitlist mortality and LT outcomes in patients with MELD 3.0 ≥ 40 to assess the potential impact of uncapping the score., Approach and Results: Adult waitlist registrations for LT from January 2016 to December 2021 were identified in the registry data from the Organ Procurement and Transplant Network. All MELD 3.0 scores were calculated at registration and thereafter. Waitlist mortality for up to 30 days was calculated as well as post-LT survival. There were 54,060 new waitlist registrations during the study period, of whom 2820 (5.2%) had MELD 3.0 ≥ 40 at listing. The 30-day waitlist mortality was high in these patients, yet it increased further in proportion with MELD 3.0 up to a score of 55 with 30-day mortality of 58.3% for MELD 3.0 of 40-44 and 82.4% for ≥50. The multivariable hazard ratio was 1.13 for each point of MELD 3.0, adjusting for several variables including acute-on-chronic liver failure. The number of LT recipients with MELD 40 at transplant increased from 155 in 2002 to 752 in 2021. Posttransplant survival was comparable across MELD strata including MELD of 35-39., Conclusion: MELD 3.0 scores beyond 40 are associated with increasing waitlist mortality without adversely affecting posttransplant outcome. Uncapping the MELD score in waitlist candidates may lead to greater survival benefit from LT., (Copyright © 2023 American Association for the Study of Liver Diseases.)