Citations

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 Members of the Transient Receptor Potential (TRP) family of ion channels have a nearly ubiquitous role in human physiology, tuning cell signaling to remarkably diverse physical and chemical stimuli. Although there is extensive structural data on TRP channels, a systematic and unbiased interrogation of structure-function relations in these proteins is required to fully elucidate their mechanisms of function. By focusing on a critical pore region of the TRPM8 channel, which is the main detector of cold and cooling agents in sensory neurons, we show how deep mutational scanning can be used in combination with the available structural data to understand how TRP channels respond to stimuli. We define a novel mechanism whereby the extracellular pore loop, which has only been resolved in structures representing desensitized states of the channel, plays an essential role in the response of TRPM8 to menthol or cold by coordinating the movement of the S6 helices that line and gate the pore, and the ion-selectivity filter that binds permeant cations. Moreover, our screen reveals sequence determinants along the S6 helices that explain how their architecture sustains gating and, together, provide strong support for a structural mechanism of TRPM8 pore opening in response to menthol and cold.

ABSTRACT Introduction Breast cancer remains a leading cause of death among Latinas. Although breast cancer risk assessment models exist and show promise in reducing mortality, few studies have elicited women's interest in and perceptions around breast cancer risk assessment, particularly among underserved populations, like Latinas, who are susceptible to disparities in breast cancer outcomes. These disparities stem from factors such as limited access to healthcare services, lower rates of screening utilization, language barriers, and socioeconomic challenges, all of which compound their risk and hinder effective engagement with risk assessment tools. This qualitative study aims to explore Latinas' perspectives regarding breast cancer risk assessment and implications on future behaviors. Methods Twenty‐three under‐ or uninsured Latinas aged 45–65 with no personal history of breast cancer took part in either a focus group ( n = 3, 15 participants) or individual interviews (8 participants). Guided by health behavior theories (Theory of Planned Behavior and Health Belief Model), data were transcribed, translated, and analyzed using a deductive‐inductive approach to thematic content analysis, resulting in four themes. Results Latinas expressed high interest in knowing their breast cancer risk and reported that the benefits of knowing one's risk outweighed the harms. Latinas also stated that they would continue screening as recommended if found to be at low risk, but that they would speak with their provider or increase screening frequency if found to be at increased risk. Moreover, Latinas described the pivotal role of providers and social networks in influencing interest and perceptions around breast cancer risk assessment and preventive behaviors. Conclusion Underserved Latinas viewed breast cancer risk assessment positively and underscored the need for multilevel, culturally tailored strategies to improve breast cancer risk assessment. This study yielded four distinct themes: (1) Interest and Awareness of Personal Breast Cancer Risk, (2) Benefits and Barriers of Knowing Personal Breast Cancer Risk, (3) Screening Implications of Knowing Personal Breast Cancer Risk, and (4) Provider Influence on Breast Cancer Risk Assessment and Behaviors. Potential strategies include efforts to improve provider engagement and communication and leveraging social networks to increase awareness and encourage preventive behaviors. Trial Registration NCI‐2023‐00465

Introduction Implementation science research increases the uptake of evidence-based interventions, which may improve health equity among racial and ethnic minorities. However, it is unclear how anti-racism and anti-colonialism practices have been integrated into implementation science research. The objectives of this scoping review are to describe the current conceptualisations of racism and colonialism within the USA, examine racism or colonialism-conscious approaches and analyse gaps in the operationalisation of anti-racism or anti-colonialism within implementation science studies. Methods and analysis This scoping review will be conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews guidelines. The Center for Chronic Disease Reduction and Equity Promotion Across Minnesota conceptual framework and an implementation science anti-racism lens will guide the study design and analysis. To determine study eligibility for the scoping review, articles will undergo abstract and full-text screening by two independent reviewers and discrepancies will be settled together. Data charting will be extracted from included articles by eight independent reviewers. The search strategy will use controlled vocabulary and natural language keywords related to health equity, health disparities and anti-racism/colonialism on six databases. The scoping review will include studies that applied implementation science theories, models or frameworks among US-based populations. Additionally, included studies will report any of the following implementation activities: implementation strategies, implementation outcomes, adaptations to evidence-based interventions, or evaluations of pre-implementation or implementation context. Ethics and dissemination No ethical approval was required for the scoping review. Dissemination will be through publication in a peer-reviewed journal and conference presentations.

Background/Objectives: Multi-cancer detection (MCD) tests have emerged as a promising tool to redefine the landscape of early cancer detection. Implementation of this novel technology will likely fall to primary care clinicians (PCC). The purpose of this study is to characterize and explore differences in PCCs perceptions and preferences towards MCD testing. Methods: Between March and May of 2023, this cross-sectional survey was administered to 281 PCCs, including physicians and advanced care providers practicing within an integrated healthcare system spanning five states. The survey collected data on self-reported characteristics, perceptions of MCD testing, and preferences for learning about MCD testing. Analysis was limited to those with no prior experience with MCD testing (N = 181, response rate 22.8%). Descriptive statistics summarized key variables and chi-square tests assessed differences in perceptions and preferences by key characteristics. Results: Most PCCs were interested in MCD testing (66.3%), but limited knowledge/awareness of MCD testing and confidence to manage patients with a positive test were observed, along with concerns around cost (76.7%) and misuse/poor implementation. The primary preferences for learning about MCD testing were online courses or classroom instruction (64.5%). Significant differences in perceptions and preferences for learning were observed by location, degree, and years in practice. Conclusions: PCCs in our study held positive views towards MCD testing, but gaps and variation in knowledge and confidence towards MCD testing and concerns around the cost and misuse/poor implementation were observed. While efforts to train and educate all PCCs on MCD testing is a critical first step, more research is needed to understand how best to support implementation tailored to individual and system-level needs and characteristics.

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.

Introduction Despite growing evidence to characterise cancer-associated cognitive decline (CACD) in women with breast cancer, interventions to mitigate CACD are limited. Emerging evidence suggests aerobic exercise may enhance cognition after breast cancer diagnosis and treatment; yet, CACD remains an understudied outcome of exercise, and few high-quality studies have been conducted. In addition to knowledge gaps in effectiveness, the translation of exercise interventions to community settings remains challenging. The Breast cancer Reasoning and Activity INtervention (BRAIN) investigates the effectiveness of aerobic exercise training, delivered in a community-based setting, for improving cognitive function in women with breast cancer and gathers information on the implementation success of the intervention. Methods and analysis This Hybrid Type I effectiveness–implementation study is conducted at an academic medical centre in the southwestern United States in partnership with a non-profit, community health and wellness organisation. The study enrols 160 women diagnosed with stage I–IIIa breast cancer and within 3–36 months of treatment completion into a 1:1 randomised controlled trial. Individuals randomised to the exercise group receive a 6-month, individually tailored aerobic exercise programme delivered by exercise trainers employed at local community fitness centres. The programme is progressive in nature and designed to help participants achieve aerobic exercise levels consistent with guidelines for cancer survivors. Individuals randomise to the control group receive a 6-month health education control intervention delivered virtually by hospital-based health educators. Cognitive performance (primary), self-reported cognition, patient-reported outcomes, physical activity and cardiorespiratory fitness are measured at baseline, 6 months (postintervention) and 12 months (follow-up). Brain structure and function are measured via magnetic resonance imaging (MRI) at baseline and 6 months. Implementation outcomes are defined by the RE-AIM framework, which includes reach, effectiveness, adoption, implementation and maintenance. RE-AIM outcomes are measured at baseline, 6 months, 12 months and ongoing during the study. Ethics and dissemination This study was approved by the Mayo Clinic Institutional Review Board (#23-000020). All participants provide informed consent prior to participation. Findings will be disseminated to scientific, clinical and community audiences through manuscripts, presentations and newsletters. Trial registration number NCT04816006.

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.

Objectives/Goals: This project will enrich our understanding of basal breast carcinogenesis, highlighting the distinct biological differences in breast cancer risk between non-Hispanic Black (NHB) or non-Hispanic White (NHW) women, but also has the potential to provide real-world solutions thereby contributing to reducing health disparities in breast cancer outcomes Methods/Study Population: In the biological investigation, I am utilizing a unique cohort of normal breast tissues from Mayo Clinic patients who underwent breast reduction surgery that have self-identified as NHB or NHW premenopausal women. From these tissues, we are able to subculture human mammary epithelial cells, which we will use for our consequent experiments. For the qualitative study, I aim to recruit up to 40–50 eligible NHB women identified at increased risk for breast cancer and conduct semi-structured qualitative interviews informed by the National Institute on Minority Health and Health Disparities Research Framework. Results/Anticipated Results: Gene expression profiling on our cohort of 15 NHB and 40 NHW premenopausal women identified a gene expression signature in NHB women indicative of elevated Hedgehog signaling, a key factor in triple-negative breast cancer (TNBC) development and progression. I hypothesize that persistent activation of Hedgehog signaling within NHB women instigates the proliferation and transformation of basal stem cells within the breast, thus fueling TNBC development. Understanding the perceptions and experiences of NHB women that are identified as being at an increased risk for BC will aid in the identification of barriers and facilitators to their risk reduction care and in turn provide implementation strategies that could contribute to alleviating the racial disparity seen in TNBC morbidity, mortality, and preventative care. Discussion/Significance of Impact: The significance of this project lies in its dual approach, uncovering basal breast cancer mechanisms in a high-risk group using normal breast tissue and evaluating the perspectives from NHB women to enhance the practical relevance of our findings.