Citations

Abstract Rationale Mechanically ventilated intensive care unit patients receive sedatives based on clinician observations of arousal and motor activity with potential for negative consequences and poor mitigation of symptoms. Objectives To test the preliminary efficacy of patient self-managed sedative therapy compared to usual care of nurse-administered sedation on self-reported anxiety, duration of mechanical ventilation, and delirium incidence (CAM-ICU). Methods A two-group, open-label, randomized, multicenter clinical trial in 5 Midwestern hospitals enrolled 161 patients receiving invasive mechanical ventilation who were willing and able to use a push-button device to self-administer sedation for up to 7 days. Patients were randomized 1:1 using center-stratified blocks to usual care (n = 81) or intervention (n = 80) with self-administered dexmedetomidine. Intervention patients were allowed 3 self-administered dexmedetomidine boluses per hour (0.25 mcg/kg) with 20-minute lock-outs. The initial basal infusion (0.2 mcg/kg/hr) was adjusted by nurses between 0.1-0.7 mcg/kg/hr based on patient-delivered boluses in the prior 2 hours. Analysis consisted of linear mixed-effects model for comparisons of anxiety ratings over time and duration of mechanical ventilation. Incidence of delirium was analyzed using generalized estimating equations. Measurement and Main Results Sample characteristics had a female (54.7%) and Caucasian preponderance (92.5%) with a median age of 62 years on protocol for a median of 88 hours. Nine intervention patients were extubated prior to protocol initiation. Patient self-reported three times daily anxiety ratings with a visual analog scale (VAS) ranged from 0-100 over time but were not significantly different between groups in either an intention-to-treat (ITT) or per protocol (PP) analysis (p = 0.94, p = 0.30 respectively). While intervention patients had shorter duration of MV [(mean 50.8(52.8) vs. usual care 68.7(58.2) hours), p = 0.02 ITT], PP analysis resulted in no difference between groups (mean 56.4 (53.0) vs. 68.7(58.2), p = 0.23). 10.2% of intervention patients developed new incidence of delirium vs. 8.5% of usual care which was not significantly different between groups by either ITT (p = 0.65) or PP analyses (p = 0.58). Conclusions Intervention patients had similar outcomes compared to usual care patients. Self-administration of sedative therapy is a safe, novel patient-centered intervention warranting further rigorous investigation for anxiety self-management.

Abstract Background Patients with breast cancer undergoing chemotherapy experience multiple symptoms that cause decrements in quality of life. A deeper understanding of serum metabolites as biomarkers may guide in predicting symptom occurrence and severity. This study evaluated change in serum metabolite levels from before chemotherapy (T1) to after the initial first or second cycle of chemotherapy (T2), after the third cycle of chemotherapy (T3) and finally after a month of chemotherapy completion (T4). Change in metabolite levels were analyzed in association with symptom occurrence. Methods Patients with breast cancer (n = 10) completed study measures at four timepoints. Neuropsychological and gastrointestinal (GI) symptoms were evaluated using the Memorial Symptom Assessment Scale. Dietary intake was assessed using the NHANES Dietary Screener Questionnaire. Serum metabolites were analyzed using gas chromatography-mass spectrophotometry. Results Five patients experienced > 3 GI symptoms at T2 and T3. At all 4 timepoints, ≥ 6 patients experienced moderate to severe neuropsychological symptoms severity. Daily mean intake of fiber, whole grain, and calcium were less than the recommended guidelines. Compared to T1, long chain fatty acid and amino acid derivative levels decreased at T2 and T3 (p < 0.05). Increase in metabolite levels of glucose-6-phosphate (p = 0.02) and 6-phosphogluconate (p = 0.05) at T2 were associated with fatigue occurrence. Conclusions Patients experienced several gastrointestinal and neuropsychological symptoms during chemotherapy and early survivorship. Chemotherapy-induced changes in metabolites involved in cellular energy metabolism may explain patient symptom experience. Metabolite level changes overtime may reflect inadequate dietary intake. Larger sample size studies may guide in building metabolic prediction models for symptom burden.

12007 Background: YAs with cancer, defined as those diagnosed prior to the age of 40, may experience greater symptom burden compared to those diagnosed at older ages. We evaluated the impact of an ePROM-triggered, CC-based, supportive care intervention on symptom burden in YAs with cancer. Methods: The Enhanced, Electronic Health Record-facilitated Cancer Symptom Control (E2C2) trial was a cluster-randomized, pragmatic trial (NCT03892967) that enrolled oncology patients seen at Mayo Clinic Rochester and within the Mayo Clinic Health System (sites in Minnesota and Wisconsin) between March 2019 and January 2023. Patients routinely reported the severity of six SPPADE symptoms (Sleep deficit, Pain, Physical function impairment, Anxiety, Depression, and Energy deficit/fatigue) on 11-point numerical rating scales. Symptom severity was classified as none to mild (0-3), moderate (4-6), or severe (7-10). Those with moderate or severe symptoms were offered symptom management education, while those with severe symptoms were also offered the option to work virtually with a symptom care manager. In this post hoc analysis, we examined the effects of the intervention on change in symptom scores among YAs and time to improvement to a mild/moderate level in those with at least one severe symptom. Results: Among 40,659 patients who responded to at least one survey, 2,598 were YAs and 38,061 were adults ≥ 40 years. Among YAs, 10.7%, 24.3%, and 65.1% were 18-24 years, 25-31 years, and 32-39 years, respectively. A greater proportion of YA patients were female (61.5% vs 57.0%), of a non-white race (12.4% vs 5.3%), living in an urban setting (65.7% vs 55.1%), single (36.4% vs 9.6%), on non-government insurance (78.1% vs 36.6%), employed (72.6% vs 37.4%), and had a Bachelor’s degree or greater (37.8% vs 28.3%, p < 0.001 for all). Fewer YA patients had metastatic disease compared to older patients (24.2% vs 35.2%, p < 0.001). Compared to a pre-intervention baseline, the mean change in symptom score for YA patients following the intervention demonstrated improvements in anxiety (-0.195) and depression (-0.168, p < 0.0001 for both), while physical function impairment worsened over the intervention period (0.101, p = 0.014). Compared to adults ≥ 40 years, YAs experienced greater intervention effects for management of depression ( p < 0.001), fatigue ( p = 0.01), pain ( p < 0.0001), and physical function impairment ( p < 0.0001). Among YAs with a severe symptom during the intervention period, median time to improvement to a mild/moderate level was longer for anxiety compared to those ≥ 40 years (3.5 vs 2.7 months, p = 0.009). Conclusions: Routine ePROM surveillance, coupled with CC-based symptom management, led to improvements in anxiety and depression among YAs with cancer, although, time to improvement was longer for anxiety compared to adults ≥ 40 years.

Abstract Background: Up to 50% of patients with breast cancer experience chemotherapy-inducednausea (CIN) and 95% experience fatigue. A comprehensive understanding of biological mechanisms remains elusive. Herein, we evaluated the association of CIN and fatigue with clinical and multi-omics features, including serum and stool metabolites before (T1) to after chemotherapy (T2). Methods: Patients with breast cancer (n=36) who were to receive chemotherapy, provided symptom assessment using the Memorial Symptom Assessment Scale, stool and blood samples at T1 and T2. Patients provided dietary intake data using a Dietary Screener Questionnaire at T1. Descriptive and univariate analyses evaluated associations of co-occurringsymptoms and diet with CIN and fatigue at T2. Gut microbiome was sequenced using shotgun metagenomics. Targeted metabolomics was performed on stool and serum. Shift in the abundance of taxonomic groups and metabolite levels from T1 to T2 were evaluated in association with CIN and fatigue. Results: Approximately 64% of the patients experienced CIN and 94% experienced fatigue atT2. Three gastrointestinal symptoms co-occurred with CIN and fatigue. Higher daily average intake of calcium (p=0.013) and dairy (p=0.035) were associated with CIN. Levels of hexosylceramides, ceramide, phosphatidylcholine and sphingomyelins were significantly perturbed in association with CIN and fatigue (p&lt;0.05). Conclusion: CIN and fatigue are associated with perturbation in the sphingolipid turnover pathway, which negatively impacts functions in the gut-liver axis that include apoptosis activity and change in bile acid levels. Confirmatory studies are warranted to support the development of interventions to alleviate CIN and fatigue in patients with breast cancer receiving chemotherapy.Keywords: breast cancer; chemotherapy-induced nausea; fatigue; metabolites; sphingolipids Citation Format: Komal Preet Singh, Brenda J. Ernst, Jun Chen, Surendra Dasari, Felipe Batalini, Cindy Tofthagen, Kathryn J. Ruddy, Keenan Pituch, Linda Chlan. Perturbations in gut liver axis functions are associated with chemotherapy induced nausea and fatigue in patients with breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6309.

Importance An estimated 70% to 80% of older adults develop delirium in the intensive care unit (ICU). Objective To determine if a slow-tempo music (60-80 beats/min) listening intervention decreases delirium duration, delirium severity, pain, or anxiety in older adults undergoing mechanical ventilation. Design, Setting, and Participants This multicenter randomized clinical trial with concealed outcomes assessments was conducted in older adults undergoing mechanical ventilation from February 2020 to December 2023. Patients were enrolled from the ICUs of 2 hospitals affiliated with the Indiana University School of Medicine and from the Mayo Clinic in Rochester, Minnesota. Intervention A music intervention comprising classical and contemporary tracks, delivered twice daily through noise-canceling headphones and tablets for up to 7 days, was compared to active control listening to a silence track delivered under identical conditions. Main Outcomes and Measures The primary outcome was delirium/coma-free days during the 7-day intervention period assessed by the Confusion Assessment Method for the ICU (CAM-ICU) and the Richmond Agitation-Sedation Scale. The secondary outcomes were delirium severity assessed by the CAM-ICU-7, pain assessed by the Critical Care Pain Observation Tool, and anxiety assessed by the visual analog scale for anxiety (VAS-A). Results A total of 158 patients were randomized (mean [SD] age, 68 (9.2) years; 72 [45.5%] female and 86 [54.4%] male). In an intention-to-treat analysis, no differences were found in the number of delirium/coma-free days in the music intervention group compared with control (median [IQR] days, 2.5 [0-5] vs 3 [0-5]; P = .66). There were also no statistically significant differences in the mean CAM-ICU-7 scores, mean pain scores, or mean VAS-A scores over the 7-day intervention period. By end of the 7-day period, both music intervention and control groups had similar mean (SD) CAM-ICU-7 scores (2.72 [2.80] vs 2.56 [2.72]), Critical Care Pain Observation Tool scores (0.20 [0.55] vs 0.61 [1.29]), and VAS-A scores (43.6 [24.7] vs 28.8 [38.4]). Conclusions and Relevance In this randomized clinical trial among older adults undergoing mechanical ventilation, a slow-tempo music intervention did not demonstrate a statistically significant decrease in delirium duration, delirium severity, pain, or anxiety symptoms. Trial Registration ClinicalTrials.gov Identifier: NCT04182334

AbstractElectronic patient-reported outcome measures (ePROMs) can improve care for people with cancer, but effectiveness hinges on well-supported integration in clinical settings.We evaluated clinician use of specific clinical decision support (CDS) tools in the electronic health record (EHR) designed to facilitate timely, clinically appropriate responses to ePROM scores for six symptoms commonly experienced by cancer patients.The parent pragmatic trial, which took place at Mayo Clinic (Rochester, Minnesota, United States) and its affiliated community health care system between March 2019 and January 2023, evaluated the population-level effectiveness and implementation of an ePROM surveillance and EHR-facilitated collaborative care symptom management intervention. The present evaluation used a case study approach with four data sources: (1) clinician interactions with CDS tools abstracted from the EHR; (2) clinician notes identified with an institution-specific textual search tool; (3) qualitative interviews and group discussions with care teams; and (4) administrative records reviewed to identify training and outreach to care teams.EHR metrics showed very low adoption of CDS tools including alerts and symptom-specific order sets, despite educational outreach and information technology support provided to clinical care teams. Qualitative findings revealed that CDS use was not easy to integrate into busy clinical workflows and highlighted clinician perceptions that the collaborative care intervention provided additional patient support that reduced clinicians' need to utilize CDS tools. They also highlight the importance of contextual factors, including institutional priorities and EHR changes.This pragmatic clinical trial case study found limited adoption of EHR CDS tools that had been developed to increase clinicians' awareness of and responses to ePROM data. Findings suggest the need to align clinician and organizational implementation strategies, simplify CDS tools to fit practice expectations, and identify and address contextual factors that could undercut strategies like education and peer support. This may be especially important for teams who aim to iteratively evaluate and refine CDS and implementation strategies for multicomponent interventions or introduce new strategies that are responsive to barriers while maintaining scalability.

This cross-sectional study analyzes patient-reported outcome findings from the Enhanced, Electronic Health Record–Facilitated Cancer Symptom Control (E2C2) trial to investigate level of symptom burden in adolescents and young adults with cancer.

AbstractThe Enhanced EHR-facilitated Cancer Symptom Control (E2C2) Trial is a pragmatic trial testing a collaborative care approach for managing common cancer symptoms. There were challenges in identifying cancer site and metastatic status.This study compares three different approaches to determine cancer site and six strategies for identifying the presence of metastasis using EHR and cancer registry data.The E2C2 cohort included 50,559 patients seen in the medical oncology clinics of a large health system. SPPADE symptoms were assessed with 0 to 10 numeric rating scales (NRS). A multistep process was used to develop three approaches for representing cancer site: the single most prevalent International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) code, the two most prevalent codes, and any diagnostic code. Six approaches for identifying metastatic disease were compared: ICD-10 codes, natural language processing (NLP), cancer registry, medications typically prescribed for incurable disease, treatment plan, and evaluation for phase 1 trials.The approach counting the two most prevalent ICD-10 cancer site diagnoses per patient detected a median of 92% of the cases identified by counting all cancer site diagnoses, whereas the approach counting only the single most prevalent cancer site diagnosis identified a median of 65%. However, agreement among the three approaches was very good (kappa > 0.80) for most cancer sites. ICD and NLP methods could be applied to the entire cohort and had the highest agreement (kappa = 0.53) for identifying metastasis. Cancer registry data was available for less than half of the patients.Identification of cancer site and metastatic disease using EHR data was feasible in this large and diverse cohort of patients with common cancer symptoms. The methods were pragmatic and may be acceptable for covariates, but likely require refinement for key dependent and independent variables.

Abstract RATIONALE: Clinical practice guidelines recommend that mechanically ventilated patients (MVPs) receiving sedative therapy achieve a target goal of ‘awake and calm’ when medically possible. However, ICU sedation practices rely on clinicians’ administration of medications based on observations of patients’ arousal/motor activity that are not consistently based on symptom assessments nor consider patients’ preferences. We hypothesized that MVPs would safely self-manage sedative therapy (SMST) base on individual needs and perceived anxiety while experiencing less sedative exposure and delirium. METHODS: A two-group randomized clinical trial conducted in two Midwestern academic medical centers enrolled 161 MVPs willing and able to depress a medication delivery push-button device who remained on protocol for 7 days or until extubated, withdrew or died. Control group (CG) patients (n=81) received sedative medications administered by ICU nurses per unit protocols. Experimental SMST group patients (n=80) received a basal infusion of dexmedetomidine (0.2 mcg/kg/hr titrated per algorithm) + self-administered bolus doses (0.25 mcg/kg up to 3/hour). Primary outcomes were anxiety ratings using a 100-mm visual analog scale (VAS-A), sedation intensity score (aggregate summary of 9 intravenous sedative/opioid medications received range 0-36), and incidence of delirium using the CAM-ICU. Analyses were descriptive and parametric statistics and Generalized Estimating Equations. RESULTS: Patients were predominantly White (93%) females (55%), mean age 58.9+15.1 years receiving mechanical ventilation for respiratory failure (60%) with mean APACHE III of 84.5 + 32.5. Anxiety was highly variable over time wherein patients in both groups endorsed the full range from 0-100. VAS-A over time between groups was -0.06 (p=0.98) indicating that anxiety was 0.06 units lower for SMST patients versus CG. Median sedation intensity in SMST group 11.8 + 9.6, compared to CG 12.7 + 9.6 (p = 0.55) over 7 days. 10.2% of SMST patients had one or more incident delirium events compared to 8.5% of CG (p =.97). Hypotension was experienced equally between groups: 22 in SMST, 23 in CG (p = 1.0) as were device disruptions: 2 in SMST versus 3 in CG (p = 1.0). 82% of SMST were satisfied/very satisfied with ability to self-administer dexmedetomidine; 70% were satisfied/very satisfied with ability to control anxiety; 68% were satisfied/very satisfied with the level of relaxation experienced. CONCLUSIONS: Although there were no significant differences between groups on the primary outcomes, the experimental SMST intervention was safe with high patient-reported satisfaction. SMST may be a viable new paradigm for sedative therapy administration among select ICU patients.