Citations

Abstract Background: Alaska Native people are committed to increasing colorectal cancer (CRC) screening to reduce the high rate of CRC in this population. We conducted a community-level cluster randomized controlled trial (RCT) to evaluate the impact of multi-target stool DNA test introduction (mt-sDNA; Cologuard® Exact Sciences, Madison WI) on CRC screening in southwest Alaska Native communities using a mt-sDNA pre-processing lab in Anchorage, Alaska. Methods: A total of 32 rural/remote Alaska Native communities were evenly randomized to either high intensity patient navigation or medium intensity mailed health education compared to 14 communities receiving standard of care (screening recommendations at health care visits). The intervention was conducted from April 2021-February 2023. Outcome measures included CRC screening completion within 12 months and method used (mt-sDNA vs colonoscopy). Results: A total of 2032 Alaska Native participants (mean [SD] age, 56 [8.4] years; 817 women [40%]) were enrolled: 587 participants randomized to usual care, 696 participants randomized to the mailed education arm, and 749 participants randomized to the patient navigation arm. The mt-sDNA test was significantly preferred over colonoscopy by both mailed education participants (68%) and patient navigation participants (71%) (p<0.01). Mt-sDNA was somewhat more preferred by older participants ages 65-75 (79%) vs younger participants ages 45-54 (64%). Both men (71%) and women (68%) significantly preferred mt-sDNA compared with colonoscopy (p<0.01). Overall, 38% of those in the patient navigation intervention completed screening compared with 33% in the mailed education intervention and 10% in the usual care arm. No significant differences were observed in mt-sDNA completion between the patient navigation arm (154 participants [40%]) and the mailed education arm (100 participants [36%]) (p= 0.34). Colonoscopy completion (not including follow-up colonoscopies after abnormal stool tests) was higher in both the patient navigation arm (112 participants [44%]) and the mailed education arm (87 participants [43%]) compared with usual care (38 participants [14%]). Over 61% of kits sent to participants were completed and returned, however, 38% of the kits were not able to be processed, primarily because of mail transit time exceeding the manufacturer’s collection-to-processing limitation of 72 hrs. Conclusions: In this RCT among Alaska Native peoples who were not up to date with CRC screening recommendations, both a mailed education intervention and a patient navigator facilitated intervention were effective at increasing CRC screening compared with usual care. Participants overwhelmingly preferred mt-sDNA for screening but limitations in getting samples to the lab in time for analysis meant that about one-third of mt-sDNA samples were unable to be processed. These findings show that screening outreach and mt-sDNA use can substantially increase CRC screening, but shipping and weather issues remain to be addressed for expanding use of mt-sDNA in rural/remote Alaskan communities. Citation Format: Diana Redwood, Christie Flanagan, Lauren Jeffries, Peter Holck, Danika Bailie, Christine Desnoyers, Joseph Klejka, Lila Rutten, John Kisiel. Increase in colorectal cancer screening among rural and remote Alaska Native peoples using the multi-target stool DNA: A randomized controlled trial [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr A148.

ABSTRACT Precision medicine approaches have gained attention for their potential to more effectively manage obesity by tailoring diagnosis and treatment strategies to individual characteristics, including genetic background, phenotypes, metabolic profiles, and environmental exposures. The current review evaluates the evidence for precision medicine in weight management by summarizing the proceedings of a Pennington Biomedical Scientific Symposium titled “Precision Prevention, Diagnostics, and Treatment of Obesity: Pipedream or Reality?” This review discusses the extent to which we can classify and predict obesity risk based on individual‐level factors; whether we have the diagnostic capability to prospectively identify people who will benefit most from specific interventions; whether prospective trials demonstrate superior prevention and treatment of obesity when precision approaches are applied; and whether evidence is sufficient to guide policy decisions. Expert opinions were presented on the current evidence of precision medicine for obesity to collectively evaluate key barriers and opportunities for implementation of precision approaches in clinical and public health settings.

Importance Advances in Alzheimer disease (AD) have shifted research focus to earlier disease stages, necessitating more scalable approaches to identify cognitively unimpaired individuals with amyloid β (Aβ) pathology. Objective To assess the utility of plasma phosphorylated tau 217 (p-tau217) for classifying Aβ status in cognitively unimpaired individuals, both as a stand-alone test and in a 2-step approach where positive plasma results were confirmed using a second modality (Aβ positron emission tomography [PET] or cerebrospinal fluid [CSF]). Design, Setting, and Participants This cross-sectional cohort study used data collected between June 2009 and March 2024. We included 2916 cognitively unimpaired participants from 12 international independent observational cohorts in the US, Europe, Australia, and Canada with available plasma p-tau217 levels and CSF or PET Aβ biomarkers. Performance comparisons between mass spectrometry and immunoassay-based p-tau217 measurements were also performed (n = 964). Exposures Plasma p-tau217 levels measured by immunoassay. Main Outcome and Measures Aβ status, determined by CSF or Aβ PET biomarkers. Results Participants had a mean (SD) age of 66.9 (9.9) years; 971 (33.3%) were Aβ positive by either CSF or PET, 1667 (57.2%) were women, and 1108 (38.1%) carried at least 1 APOE ε4 allele. As a stand-alone test, plasma p-tau217 achieved a positive predictive value (PPV) of 79% (95% CI, 74-84) and an overall accuracy of 81% (95% CI, 80-82). In a 2-step workflow, the PPV and accuracy significantly increased to 91% (95% CI, 86-95). While this approach required screening of 677 individuals with plasma p-tau217 to identify 100 Aβ-positive individuals, compared to 536 participants when using PET alone, it reduced the need for PET testing to 124. Immunoassays demonstrated comparable PPVs to mass spectrometry (80% [95% CI, 74-86] vs 85% [95% CI, 81-90]; P = .12) but significantly lower overall accuracy (82% [95% CI, 79-84]% vs 88 [95% CI, 86-90]; P < .001) and true Aβ-positive detection rate (49% [95% CI, 43-55] vs 69% [95% CI, 64-75]; P < .001). Conclusions and Relevance The findings highlight the potential of plasma p-tau217 as a stand-alone test—or when used in a sequential 2-step approach alongside PET or CSF testing—as a cost-effective, scalable, and minimally burdensome strategy for identifying preclinical AD. Tailored screening workflows that incorporate p-tau217 can improve efficiency in participant selection for preclinical AD trials and, in the future, help guide access to disease-modifying treatments.

Background: There is little data available in infants on the extent to which inhalational anesthetics prolong the effects of neuromuscular blocking agents compared with intravenous agents. Here, we assessed the differences between the neuromuscular blocking effects (duration and recovery time) of a single dose of rocuronium during propofol vs. sevoflurane anesthesia. Methods: The prospective study enrolled 20 infants (4–12 months of age) scheduled for craniosynostosis surgery, randomly assigned to receive general anesthesia maintenance with sevoflurane or propofol. All patients received 0.6 mg/kg rocuronium as a single bolus dose to facilitate tracheal intubation and surgery. Primary study endpoint was the clinical duration of rocuronium, from administration until spontaneous recovery to a train-of-four ratio (TOFR) > 0.90. Secondary endpoints were times for reappearance of the first, second, third, and fourth twitches of the TOF (T1, T2, T3 and T4, respectively) in the two patient groups. Results: There were no differences in the infants’ age (sevoflurane maintenance: 5.8 ± 2.4 months; propofol maintenance: 6.7 ± 3.1 months, p = 0.47) or weight (sevoflurane: 7722 ± 1644 g; propofol: 7433 ± 1782 g, p = 0.71). Rocuronium onset time was 101.0 ± 55.0 s in the sevoflurane group and 83.4 ± 47.9 s in the propofol group (p = 0.46). Total duration of anesthesia was comparable in the sevoflurane (122.0 ± 23.8 min) and propofol (107.7 ± 25.2 min, p = 0.18) groups. Rocuronium recovery to TOFR > 0.9 required 136 min (CI: 123.7–149.5 min) in the sevoflurane group and 61.5 min (CI: 58.0–101.0 min) in the propofol group (p < 0.001). Conclusions: In infants, sevoflurane maintenance enhances the neuromuscular blocking effect of a single, 0.6 mg/kg BW dose of rocuronium as compared to propofol maintenance. After discontinuation of sevoflurane, additional time is necessary to reach the acceptable TOFR >0.9 needed before tracheal extubation. The present study further underscores the importance of objective (quantitative) neuromuscular monitoring in infants to guide intraoperative management and prevent residual neuromuscular block.

Abstract Background and Aims Intestinal ultrasound (IUS) is increasingly used to monitor treatment efficacy in inflammatory bowel disease (IBD) trials. However, standardized definitions for response, remission, and optimal assessment timing remain undefined. An international expert consensus meeting was held to establish IUS endpoints for clinical trials. Methods A panel of 35 international gastroenterologists and radiologists participated in a modified Delphi process, reviewing the literature and developing consensus statements. Agreement was defined as at least 75% consensus. Results Consensus was reached on 150 statements across four domains: general IBD (30 statements), luminal Crohn’s disease (CD) (43), perianal CD (51), and ulcerative colitis (UC) (26). For luminal CD and UC, ultrasound response was defined by: (1) a ≥25% reduction in bowel wall thickness (BWT) from baseline, or (2) multifactorial improvement, combining BWT reduction with ≥1 grade decrease in color Doppler signal (CDS) or another IUS parameter. Assessments were set at weeks 4-8 for the colon and week 12 for the terminal ileum. Ultrasound remission in luminal CD was defined as: (1) BWT normalization (≤3 mm) or (2) normalization of multiple parameters, including BWT, CDS, and all other IUS parameters. Similar remission criteria were proposed for UC, but the sigmoid BWT normal range (3-4 mm) remained uncertain. The bowel ultrasound score (BUSS) for CD and the Milan ultrasound criteria (MUC) for UC were supported as standardized scoring systems for trials. Conclusion This consensus provides standardized IUS definitions to enhance consistency in IBD trials, supporting the integration of IUS in future research.

Abstract Objective This study aims to better characterize the long‐term neurological quality of life (QOL) outcomes (using the Neuro‐QOL scale) in survivors of new onset refractory status epilepticus (NORSE), including its subtype febrile infection‐related epilepsy syndrome (FIRES), and provide guidance for psychological and social support strategies. Methods Utilizing data from a multicenter prospective study of NORSE/FIRES led by Yale University, we enrolled patients who completed the validated, patient‐reported Neuro‐QOL scale at least once at 3–6 months ( n = 37), 12 months ( n = 29), 24 months ( n = 23), or ≥36 months ( n = 9) following discharge. The Neuro‐QOL scale assesses physical, mental, and social health in patients with neurological disorders. QOL impairment (QOL‐I) scores were calculated, with higher scores indicating greater impairment. T ‐scores enabled comparisons with reference populations. Results In adults, median QOL‐I improved from 44.1% at 3–6 months to 37.6% at 36+ months. Paired analysis showed significant improvement in QOL‐I between 3–6 and 24 months ( p = .016), with specific improvements in communication, satisfaction with social roles, fatigue, and mobility. Greater improvement was also observed for participation in social roles (5.5‐point T ‐score gain) compared to the reference population, suggesting meaningful change. A gradual improvement in overall QOL‐I scores was also observed in pediatric participants, despite a modest sample size ( n = 5 with data at 3–6 and 12 months). Measures of fatigue and anxiety persisted in adults, and cognitive difficulties persisted in both adults and children. In adults, longer status epilepticus duration and intensive care unit stay were associated with poorer QOL. Additionally, a higher number of antiseizure medications was associated with more depression, cognitive impairments, and perceived stigma. Significance These findings highlight the potential for recovery following an acute episode of NORSE, although many patients continue to face challenges requiring ongoing support, and the clinical meaning of the reported QOL improvement remains unclear. Furthermore, the findings underscore the importance of strategic multidisciplinary support systems in the years following discharge.

Abstract Electronic portal imaging devices (EPIDs) have been in widespread clinical use for almost two decades due to favorable measurement characteristics such as fast image acquisition, high sensitivity and resolution, digital data format, long‐term stability, linear dose response, and large detection area. On‐board EPIDs are widely used as a quality assurance (QA) tool to monitor nearly every aspect of linear accelerator (linac) performance. In both the commercial QA equipment market and in clinical practice, there is a trend toward replacing conventional QA approaches with fully automated, EPID‐based QA tools. Despite widespread use, EPIDs are complex devices, and there has yet to be consensus or formal recommendations published by the AAPM for their use in routine linac QA. Task Group 330 (TG‐330) was, therefore, formed to provide guidelines and recommendations for physicists on the safe and appropriate use of EPIDs for linac QA. In particular, the report: (a) provides a comprehensive review of the characteristics and limitations of EPIDs as time‐resolved measurement devices and dosimeters; (b) summarizes the application of EPIDs for linac QA; (c) provides recommendations on efficient and effective implementations of EPID‐based QA techniques; (d) describes risks associated with the use of EPIDs for linac QA and provides examples of how risk analysis can be used to ensure the safe use of EPIDs for linac QA. Many of the guidelines in this report are drawn from the literature that is included in the references and from the collective experience of the task group members. This report does not provide recommendations on the implementation of EPID‐based patient‐specific IMRT or VMAT QA, which is the topic of AAPM's report from AAPM TG‐307.

ABSTRACT Introduction Etripamil is a fast‐acting intranasally self‐administered calcium‐channel blocker developed for termination of paroxysmal supraventricular tachycardia (PSVT). Prior studies have demonstrated safety and efficacy of etripamil for PSVT termination following an initial medically supervised test dose during sinus rhythm. NODE‐303 is an open‐label, single‐arm study that evaluated etripamil for multiple, at‐home PSVT episodes, without test dose before first use. Methods Patients applied an ECG monitor at symptom onset and self‐administered etripamil (70 mg) if a vagal maneuver was unsuccessful. ECG monitoring occurred for ≥ 1 h following study drug administration. A repeat 70‐mg dose was introduced during the study for symptoms persisting 10 min after the first dose. Safety measures included treatment‐emergent adverse events (TEAEs) and ECG arrhythmia‐surveillance. Efficacy measures were captured for PSVT termination during treatment of each of the multiple episodes. Results 1054 perceived PSVT episodes were etripamil‐treated in 503 of 1116 patients enrolled. TEAEs within 24 h were mostly mild or moderate and localized: 30.2% of patients experienced nasal discomfort, nasal congestion (13.9%), rhinorrhea (13.1%), epistaxis (7.4%). TEAE frequencies decreased across multiple PSVT episodes and were similar for single versus repeat doses. For first PSVT episodes, 70.5% of patients converted to sinus rhythm by 60 min post etripamil (median time to conversion = 18.3 min [14.2–25.6]). Conversion in earlier episodes was consistently predictive of conversion in subsequent episodes. Conclusions Etripamil nasal spray self‐administered in a real‐world setting was well tolerated, effective, and had a consistent safety profile as a single‐ or repeat‐dose regimen across multiple PSVT episodes. Trial Registration: ClinicalTrials.gov NCT04072835