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PURPOSE The adjuvant treatment for stage III colon cancer (CC) is chemotherapy combining fluoropyrimidine (FP) and oxaliplatin (OX). FP regimen plus OX (FPOX) may benefit in high-risk stage II CC. We performed a pooled analysis of pivotal MOSAIC and C-07 studies evaluating FPOX for the treatment of high-risk stage II CC according to prognostic factors, number of high-risk factors, and current clinicopathologic risk classification on the basis of T stage, tumor perforation, and number of lymph nodes examined. PATIENTS AND METHODS One thousand five hundred and ninety-five patients with stage II CC receiving FP or FPOX were pooled. The overall survival (OS) benefit of OX was analyzed using Kaplan-Meier curves and unadjusted Cox models stratified by study. Three thousand and fifty-nine patients with stage III CC were used only for interaction tests between the allocated chemotherapy and stage. RESULTS In the pooled analysis of stage II patients, independent prognostic factors in multivariable analysis were sex, age, perforation/obstruction, and tumor sidedness. There was a significant interaction in OS between stage and allocated chemotherapy with hazard ratios (HRs) of 1.03 for stage II (95% CI, 0.82 to 1.29; P = .813) and 0.82 for stage III (95% CI, 0.73 to 0.92; P = .001; P int = .073). There was no benefit from the addition of OX to FP for any of the prognostic factors. The number of high-risk factors tested was not predictive of OX benefit. According to the currently agreed clinicopathologic risk classification, no OS benefit of OX was observed, as HR was 0.86 (95% CI, 0.63 to 1.18; P = .349). CONCLUSION No OS benefit of adjuvant OX was found in high-risk stage II CC, regardless of the definition used to characterize tumors as having a high risk for recurrence. Hence, our analysis suggests that OX should not be the standard of care for adjuvant chemotherapy for stage II CC, even in high-risk patients.

AbstractBackgroundIrritable bowel syndrome (IBS) is a disorder of gut–brain interaction characterized by abdominal pain and altered bowel habits, with patient‐perceived dissatisfaction of treatment symptom control. We assessed disease burden, satisfaction with medication use, and impact on activities, in participants with IBS with constipation (IBS‐C) and diarrhea (IBS‐D).MethodsThis study assessed data from a large, United States survey of adults querying demographics, comorbid conditions, quality of life, medication use, satisfaction with symptom control, and work productivity. Participants were grouped into the IBS‐C or IBS‐D cohort if they met Rome IV criteria, with controls matched 1:1 according to age, sex, race, region, and Charlson Comorbidity Index score. All data were self‐reported.Key ResultsNine hundred and ten participants with IBS‐C and 669 with IBS‐D were matched to controls. The most reported symptoms were abdominal discomfort for IBS‐C and abdominal pain and abdominal discomfort for IBS‐D. Among the IBS‐C and IBS‐D cohorts, 74.2% and 65.9%, respectively, took prescription and/or over‐the‐counter medication for their symptoms. Respondents were more dissatisfied than satisfied with control of their symptoms. Respondents taking prescription medication(s) with or without over‐the‐counter medication(s) reported better symptom control than respondents only taking over‐the‐counter medications (p < 0.001). There was significantly higher mean presenteeism, work productivity loss, and daily activity impairment (p < 0.001 for all) in respondents with IBS compared with controls.Conclusions and InferencesThis study provides insight into respondents' experiences of IBS symptoms, including the impact on daily activity, as well as satisfaction with control of symptoms and prescription and over‐the‐counter medications.

AbstractINTRODUCTIONWe evaluated preliminary feasibility of a digital, culturally‐informed approach to recruit and screen participants for the Alzheimer's Disease Neuroimaging Initiative (ADNI4).METHODSParticipants were recruited using digital advertising and completed digital surveys (e.g., demographics, medical exclusion criteria, 12‐item Everyday Cognition Scale [ECog‐12]), Novoic Storyteller speech‐based cognitive test). Completion rates and assessment performance were compared between underrepresented populations (URPs: individuals from ethnoculturally minoritized or low education backgrounds) and non‐URPs.RESULTSOf 3099 participants who provided contact information, 654 enrolled in the cohort, and 595 completed at least one assessment. Two hundred forty‐seven participants were from URPs. Of those enrolled, 465 met ADNI4 inclusion criteria and 237 evidenced possible cognitive impairment from ECog‐12 or Storyteller performance. URPs had lower ECog and Storyteller completion rates. Scores varied by ethnocultural group and educational level.DISCUSSIONPreliminary results demonstrate digital recruitment and screening assessment of an older diverse cohort, including those with possible cognitive impairment, are feasible. Improving engagement and achieving educational diversity are key challenges.Highlights A total of 654 participants enrolled in a digital cohort to facilitate ADNI4 recruitment. Culturally‐informed digital ads aided enrollment of underrepresented populations. From those enrolled, 42% were from underrepresented ethnocultural and educational groups. Digital screening tools indicate > 50% of participants likely cognitively impaired. Completion rates and assessment performance vary by ethnocultural group and education.

ImportanceTranexamic acid reduces bleeding and blood transfusion in many types of surgery, but its effect in patients undergoing liver resection for a cancer-related indication remains unclear.ObjectiveTo determine whether tranexamic acid reduces red blood cell transfusion within 7 days of liver resection.Design, Setting, and ParticipantsMulticenter randomized clinical trial of tranexamic acid vs placebo conducted from December 1, 2014, to November 8, 2022, at 10 hepatopancreaticobiliary sites in Canada and 1 site in the United States, with 90-day follow-up. Participants, clinicians, and data collectors were blinded to allocation. A volunteer sample of 1384 patients undergoing liver resection for a cancer-related indication met eligibility criteria and consented to randomization.InterventionsTranexamic acid (1-g bolus followed by 1-g infusion over 8 hours; n = 619) or matching placebo (n = 626) beginning at induction of anesthesia.Main Outcomes and MeasuresThe primary outcome was receipt of red blood cell transfusion within 7 days of surgery.ResultsThe primary analysis included 1245 participants (mean age, 63.2 years; 39.8% female; 56.1% with a diagnosis of colorectal liver metastases). Perioperative characteristics were similar between groups. Red blood cell transfusion occurred in 16.3% of participants (n = 101) in the tranexamic acid group and 14.5% (n = 91) in the placebo group (odds ratio, 1.15 [95% CI, 0.84-1.56]; P = .38; absolute difference, 2% [95% CI, −2% to 6%]). Measured intraoperative blood loss (tranexamic acid, 817.3 mL; placebo, 836.7 mL; P = .75) and total estimated blood loss over 7 days (tranexamic acid, 1504.0 mL; placebo, 1551.2 mL; P = .38) were similar between groups. Participants receiving tranexamic acid experienced significantly more complications compared with placebo (odds ratio, 1.28 [95% CI, 1.02-1.60]; P = .03), with no significant difference in venous thromboembolism (odds ratio, 1.68 [95% CI, 0.95-3.07]; P = .08).Conclusions and RelevanceAmong patients undergoing liver resection for a cancer-related indication, tranexamic acid did not reduce bleeding or blood transfusion but increased perioperative complications.Trial RegistrationClinicalTrials.gov Identifier: NCT02261415

AbstractBackgroundChronic idiopathic constipation (CIC) is a disorder of gut–brain interaction characterized by a variety of bowel movement‐related and abdominal symptoms. A greater understanding of medication use and satisfaction with symptom control may provide insights to optimize patient care. Therefore, we explored these aspects of the disorder in adults with CIC.MethodsThis study assessed data collected from a large nationwide survey of adult participants in the United States, querying demographics, clinical characteristics, and comorbid conditions, as well as medication use, care‐seeking behaviors, and satisfaction with symptom control. Participants were grouped into the CIC cohort if they met Rome IV criteria, with controls matched 1:1 according to age, sex, race, region, and Charlson Comorbidity Index score. All data were self‐reported.Key ResultsTwo thousand five hundred and thirty‐three participants with CIC were matched 1:1 to controls. In the CIC cohort, abdominal pain was the most reported symptom leading to medication use: 15.9% of respondents were receiving a prescription medication in addition to an over‐the‐counter medication, while 26.3% were taking neither. In addition, only one‐third were satisfied with the control of their symptoms; however, satisfaction was significantly higher in respondents taking a prescription medication (p < 0.001). The proportion of reported comorbidities was significantly higher in the CIC cohort versus the control cohort, with chronic pain, anxiety, and depression among the highest (p < 0.001 for all).Conclusions and InferencesThis study emphasizes the need for better communication regarding prescription medications and their benefits, with the goal of further improving CIC patients' overall symptoms.

OBJECTIVE This study aimed to assess the need for practice-wide quality improvement to support evidence-based type 2 diabetes screening for women with a history of gestational diabetes mellitus (GDM) receiving primary care. We sought to add the diagnosis of GDM to the problem list of women who did not have it at baseline. RESEARCH DESIGN AND METHODS We identified all women in our practice with a history of GDM diagnosed between 2002 and 2023, quantified the proportion with GDM documented in their problem list, and examined patient- and clinician-level factors associated with having GDM appropriately documented at baseline. RESULTS We identified 203 women with GDM receiving primary care within internal medicine. Of the 203 women, 73 (35.0%) did not have GDM documented in their problem list. Of those without GDM included on the problem list, 52% were overdue for type 2 diabetes screening compared with 41% of those with GDM documented before our intervention. We found race, parity, and previous abnormal glycemic laboratory test results to be highly predictive of whether the history of GDM was on patients’ problem list. Upon completion of our intervention, we successfully achieved a 100% documentation rate for GDM diagnosis for women who previously lacked documentation in their problem list. CONCLUSION This work paves the way for targeted interventions aimed at improving care for women with a history of GDM, including delivery of interventions and education to prevent the onset of an appropriate clinical screening for type 2 diabetes.

Background Endovascular treatment with the woven endobridge (WEB) device has been widely utilized for managing intracranial aneurysms. However, predicting the probability of achieving adequate occlusion (Raymond–Roy classification 1 or 2) remains challenging. Objective Our study sought to develop and validate a predictive calculator for adequate occlusion using the WEB device via data from a large multi-institutional retrospective cohort. Methods We used data from the WorldWide WEB Consortium, encompassing 356 patients from 30 centers across North America, South America, and Europe. Bivariate and multivariate regression analyses were performed on a variety of demographic and clinical factors, from which predictive factors were selected. Calibration and validation were conducted, with variance inflation factor (VIF) parameters checked for collinearity. Results A total of 356 patients were included: 124 (34.8%) were male, 108 (30.3%) were elderly (≥65 years), and 118 (33.1%) were current smokers. Mean maximum aneurysm diameter was 7.09 mm (SD 2.71), with 112 (31.5%) having a daughter sac. In the multivariate regression, increasing aneurysm neck size (OR 0.706 [95% CI: 0.535–0.929], p = 0.13) and partial aneurysm thrombosis (OR 0.135 [95% CI: 0.024–0.681], p = 0.016) were found to be the only statistically significant variables associated with poorer likelihood of achieving occlusion. The predictive calculator shows a c-statistic of 0.744. Hosmer–Lemeshow goodness-of-fit test indicated a satisfactory model fit with a p-value of 0.431. The calculator is available at: https://neurodx.shinyapps.io/WEBDEVICE/ . Conclusion The predictive calculator offers a substantial contribution to the clinical toolkit for estimating the likelihood of adequate intracranial aneurysm occlusion by WEB device embolization.

ImportanceBlack or African American (hereinafter, Black) and Hispanic or Latino/a/x (hereinafter, Latinx) adults are disproportionally affected by Alzheimer disease, but most research studies do not enroll adequate numbers of both of these populations. The Alzheimer’s Disease Neuroimaging Initiative-3 (ADNI3) launched a diversity taskforce to pilot a multipronged effort to increase the study inclusion of Black and Latinx older adults.ObjectiveTo describe and evaluate the culturally informed and community-engaged inclusion efforts to increase the screening and enrollment of Black and Latinx older adults in ADNI3.Design, Setting, and ParticipantsThis cross-sectional study used baseline data from a longitudinal, multisite, observational study conducted from January 15, 2021, to July 12, 2022, with no follow-up. The study was conducted at 13 ADNI3 sites in the US. Participants included individuals aged 55 to 90 years without cognitive impairment and those with mild cognitive impairment or Alzheimer disease.ExposuresEfforts included (1) launch of an external advisory board, (2) changes to the study protocol, (3) updates to the digital prescreener, (4) selection and deployment of 13 community-engaged research study sites, (5) development and deployment of local and centralized outreach efforts, and (6) development of a community-science partnership board.Main Outcomes and MeasuresScreening and enrollment numbers from centralized and local outreach efforts, digital advertisement metrics, and digital prescreener completion.ResultsA total of 91 participants enrolled in the trial via centralized and local outreach efforts, of which 22 (24.2%) identified as Latinx and 55 (60.4%) identified as Black (median [IQR] age, 65.6 [IQR, 61.5-72.5] years; 62 women [68.1%]). This represented a 267.6% increase in the monthly rate of enrollment (before: 1.11 per month; during: 4.08 per month) of underrepresented populations. For the centralized effort, social media advertisements were run between June 1, 2021, and July 31, 2022, which resulted in 2079 completed digital prescreeners, of which 1289 met criteria for subsequent site-level screening. Local efforts were run between June 1, 2021, to July 31, 2022. A total of 151 participants underwent site-level screening (100 from local efforts, 41 from centralized efforts, 10 from other sources).Conclusions and RelevanceIn this cross-sectional study of pilot inclusion efforts, a culturally informed, community-engaged approach increased the inclusion of Black and Latinx participants in an Alzheimer disease cohort study.

Background As no consensus exists on the optimal postoperative rehabilitation protocol in terrible triad injuries, we sought to characterize the reported protocols and relate them to postoperative range of motion (ROM) measures and Mayo Elbow Performance Score (MEPS). Methods A systematic review was performed by searching PubMed/MEDLINE, Embase, Web of Science, and Cochrane databases to identify articles on the operative treatment of terrible triad injuries reporting postoperative rehabilitation protocols were included. Included studies were descriptively summarized. Methodologic quality was assessed using the Methodological Index for Non-randomized Studies criteria. Meta-analysis compared postoperative ROM measures and the MEPS between patients initiating passive ROM exercises at ≤7 days vs. >7 days. Results Our review included 36 articles with 1123 elbows (66% male, mean age: 43 years, follow-up: 27 months). Of the studies reporting physical therapy protocols, it was most commonly initiated at 7 days postoperatively (6/36, 17%), passive ROM exercises at 7 days (3/25, 12%), and active ROM at 21 days (4/26, 15%). On meta-analysis, early passive ROM initiation was not associated with improved elbow ROM or MEPS. Discussion While rehabilitation protocols commonly advised passive ROM at one week post-operatively, meta-analysis did not support functional benefits of early passive ROM. Study design Systematic Review; Level of evidence, 4.