Patient-reported Symptoms Research Articles

Impact of SARS-CoV-2 Infection on Long-Term Depression Symptoms among Veterans

BackgroundPrior research demonstrates that SARS-COV-2 infection can be associated with a broad range of mental health outcomes including depression symptoms. Veterans, in particular, may be at elevated risk of increased depression following SARS-COV-2 infection given their high rates of pre-existing mental and physical health comorbidities. However, few studies have tried to isolate SARS-COV-2 infection associations with long term, patient-reported depression symptoms from other factors (e.g., physical health comorbidities, pandemic-related stress).ObjectiveTo evaluate the association between SARS-COV-2 infection and subsequent depression symptoms among United States Military Veterans.DesignSurvey-based non-randomized cohort study with matched comparators.ParticipantsA matched-dyadic sample from a larger, stratified random sample of participants with and without known to SARS-COV-2 infection were invited to participate in a survey evaluating mental health and wellness 18-months after their index infection date. Sampled participants were stratified by infection severity of the participant infected with SARS-COV-2 (hospitalized or not) and by month of index date. A total of 186 participants in each group agreed to participate in the survey and had sufficient data for inclusion in analyses. Those in the uninfected group who were later infected were excluded from analyses.Main MeasuresParticipants were administered the Patient Health Questionnaire-9 as part of a phone interview survey. Demographics, physical and mental health comorbidities were extracted from VHA administrative data.Key ResultsVeterans infected with SARS-COV-2 had significantly higher depression symptoms scores compared with those uninfected. In particular, psychological symptoms (e.g., low mood, suicidal ideation) scores were elevated relative to the comparator group (MInfected = 3.16, 95%CI: 2.5, 3.8; MUninfected = 1.96, 95%CI: 1.4, 2.5). Findings were similar regardless of history of depression.ConclusionSARS-COV-2 infection was associated with more depression symptoms among Veterans at 18-months post-infection. Routine evaluation of depression symptoms over time following SARS-COV-2 infection is important to facilitate adequate assessment and treatment.

Association between vertebral endplate defects and patient-reported symptoms: an immunohistochemical study investigating the COX-2/PGE-2/EP-4 axis

Background ContextVertebral endplate defects are often implicated in degenerative disc disorders, yet their connection to patient-reported symptoms remains unclear. COX-2 and PGE-2 are known for their roles in inflammation and pain, with EP-4 receptor involvement in pain signaling. Examining their expression in vertebral endplate tissues may provide insights into pathomechanism of low back pain. PurposeTo investigate the association between endplate defects and patient-reported symptoms and to further clarify the role of the COX-2/PGE-2/EP-4 axis in the pathogenesis of chronic low back pain. Study Design/SettingRetrospective study. Patient SampleA total of 71 patients who had undergone single-level L4/5 or L5/S1 modified laminectomy decompression preserving proximal upper laminae and transforaminal lumbar interbody fusion surgery were included in this study, including 18 patients diagnosed with lumbar disc herniation, 19 with lumbar disc herniation accompanied by degenerative lumbar spinal stenosis, and 34 with degenerative spondylolisthesis. Outcome MeasuresDemographic data, Pfirrmann grade, Modic changes, endplate defect score, visual analog scale (VAS) for back and leg pain, and Oswestry Disability Index (ODI) before surgery, 3-month and 6-month follow-up, and the percentage of immune-positive cells (COX-2, PGE-2, and EP-4) in endplate tissue sections. MethodsPatients were divided into defect and nondefect groups according to endplate morphology on lumbar MR. All intraoperative endplate specimens were immediately fixed in 10% formaldehyde, and then embedded in paraffin 3 days later for tissue sections. The outcome measures were compared between the defect group and nondefect group. Data were analyzed using independent t-tests and χ² tests. Pearson's rank correlation test was used to assess correlations between patient-reported symptoms and the percentage of immune-positive cells in the groups. Multivariable logistic regression models using the forward stepwise likelihood ratio method were used to identify the factors that were independently associated with endplate defects. ResultsThe age of Defect group was significantly higher than that of nondefect group (52.5±7.7 vs 57.2±9.1. p=.024). There were no significant differences in gender, diagnosis, BMI, comorbidities, or surgical level between the two groups. Modic changes (Type Ⅱ/Type Ⅲ) were more common in patients of Defect group than nondefect group (38.5% vs 11.1%, p<.001), and so was disc degeneration (Pfirrmann grade Ⅳ/Ⅴ) (69.2% vs 33.3%, p<.001). Defect group had significantly higher VAS-Back (6.5±2.0 vs 4.9±1.6, p<.001) and ODI scores (62.9±10.7 vs 45.2±14.8, p<.001) than nondefect group, while there was no significant differences between the two groups during the 3 and 6-month follow-up after surgery. Histologically, Defect group was characterized by upregulation of COX-2, PGE-2, and EP-4 in endplate tissue sections. Both in defect and nondefect groups, VAS-Back showed moderate positive correlations with the expressions of COX-2 (r=0.643; r=0.558, p both<.001), PGE-2 (r=0.611; r=0.640, p both<.001), and EP-4 (r=0.643; r=0.563, p both<.001). Multivariate regression analyses reveled that percentage of COX-2-positive cells was associated with endplate defects (OR=1.509, 95%CI [1.048–2.171], p=.027), as well as percentage of PGE-2-positive (OR=1.291, 95%CI [1.106–1.508], p=.001) and EP-4-positive cells (OR=1.284, 95%CI [1.048∼2.171], p=.003). ConclusionsPatients with endplate defects had worse quality of life, more severe disc degeneration and Modic changes, and up-regulated COX-2/PGE-2/EP-4 axis expression in cartilage endplates in patients with defected endplates. Inflammatory factors may significantly contribute to the onset and progression of chronic low back pain in patients with endplate defects, consequently impacting patient-reported symptoms.

Patient-Reported Sinonasal Symptoms and Risk of Relapse in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Relapses are frequent and difficult to predict in antineutrophil cytoplasmic antibody-associated vasculitis (AAV), resulting in long-term use of immunosuppression. Although sinonasal disease is associated with relapse of AAV, detailed characterization of sinonasal symptoms is lacking. Using a patient-reported outcome, the 22-item SinoNasal Outcome Test (SNOT-22), we investigated the relationship between sinonasal symptoms and disease activity in AAV. This was a prospective, longitudinal study of individual with AAV and healthy individuals. Relapse was defined as a Birmingham Vasculitis Activity Score for Wegner's Granulomatosis score >0. Higher SNOT-22 scores indicate worse symptoms. Generalized estimating equation and Cox proportional hazard models evaluated the association between SNOT-22 and relapse. There were 773 visits (106 active disease visits) from 168 patients with AAV and 51 controls. Median SNOT-22 at remission was higher in AAV versus controls (20 vs 5; P < 0.001) and higher during active disease versus remission (P < 0.001). In all AAV, and particularly within granulomatosis with polyangiitis, higher SNOT-22 scores were observed months to years before relapse and were associated with increased risk of relapse (hazard ratio 2.7, 95% confidence interval 1.2-6.2; P = 0.02). Similar findings were seen when examining patients with versus without sinonasal disease and after removing relapses limited to the ear, nose, and throat. A patient-reported outcome measure of sinonasal disease, the SNOT-22, not only changes with disease activity in AAV, but also is associated with a higher risk of relapse within two years. These findings support the possibility that the SNOT-22 score may enhance prediction of relapse and that persistent sinonasal disease may be important in the pathophysiology of relapse.

Ankle inversion proprioception measured during stair descent can identify chronic ankle instability

BackgroundIndividuals with chronic ankle instability (CAI) may experience recurrent ankle sprains and symptoms during daily activities such as stair descent, where the associated proprioceptive deficit is largely unevaluated. ObjectivesTo evaluate the reliability and validity of an ankle inversion discrimination apparatus for stair descent, and examine whether proprioceptive scores from this apparatus are associated with patient-reported symptoms. DesignCross-sectional study. MethodSixty-six participants volunteered in this study. The ankle inversion discrimination apparatus was purpose-built to assess ankle proprioception across four positions of ankle inversion (10°, 12°, 14°, and 16°) during stair descent. The Area Under the Receiver Operating Curve (AUC) was employed as the ankle proprioceptive discrimination score. ResultsTest-retest reliability ICC (3,1) for the whole group was 0.825, with 0.747 for the non-CAI group (95%CI = 0.331–0.920) and 0.701 for CAI (95%CI = 0.242–0.904). The CAI group performed at a significantly lower level than non-CAI on the ankle inversion discrimination apparatus for stair descent assessment (0.769 ± 0.034 vs. 0.830 ± 0.035, F = 33.786, p < 0.001). CAIT scores were strongly and significantly correlated with scores from this apparatus (Spearman's rho = 0.730, p < 0.001). ConclusionsThe ankle inversion discrimination apparatus for stair descent is reliable and valid for assessing task-specific ankle proprioceptive impairments in CAI. The strong and significant relationship found between ankle proprioception during stair descent and the severity of CAI suggests that rehabilitation programs focusing on deficits in ankle inversion proprioception during stair descent may improve self-reported instability in CAI.

Novel Approach for Detecting Respiratory Syncytial Virus in Pediatric Patients Using Machine Learning Models Based on Patient-Reported Symptoms: Model Development and Validation Study.

Respiratory syncytial virus (RSV) affects children, causing serious infections, particularly in high-risk groups. Given the seasonality of RSV and the importance of rapid isolation of infected individuals, there is an urgent need for more efficient diagnostic methods to expedite this process. This study aimed to investigate the performance of a machine learning model that leverages the temporal diversity of symptom onset for detecting RSV infections and elucidate its discriminatory ability. The study was conducted in pediatric and emergency outpatient settings in Japan. We developed a detection model that remotely confirms RSV infection based on patient-reported symptom information obtained using a structured electronic template incorporating the differential points of skilled pediatricians. An extreme gradient boosting-based machine learning model was developed using the data of 4174 patients aged ≤24 months who underwent RSV rapid antigen testing. These patients visited either the pediatric or emergency department of Yokohama City Municipal Hospital between January 1, 2009, and December 31, 2015. The primary outcome was the diagnostic accuracy of the machine learning model for RSV infection, as determined by rapid antigen testing, measured using the area under the receiver operating characteristic curve. The clinical efficacy was evaluated by calculating the discriminative performance based on the number of days elapsed since the onset of the first symptom and exclusion rates based on thresholds of reasonable sensitivity and specificity. Our model demonstrated an area under the receiver operating characteristic curve of 0.811 (95% CI 0.784-0.833) with good calibration and 0.746 (95% CI 0.694-0.794) for patients within 3 days of onset. It accurately captured the temporal evolution of symptoms; based on adjusted thresholds equivalent to those of a rapid antigen test, our model predicted that 6.9% (95% CI 5.4%-8.5%) of patients in the entire cohort would be positive and 68.7% (95% CI 65.4%-71.9%) would be negative. Our model could eliminate the need for additional testing in approximately three-quarters of all patients. Our model may facilitate the immediate detection of RSV infection in outpatient settings and, potentially, in home environments. This approach could streamline the diagnostic process, reduce discomfort caused by invasive tests in children, and allow rapid implementation of appropriate treatments and isolation at home. The findings underscore the potential of machine learning in augmenting clinical decision-making in the early detection of RSV infection.

Patient adherence and response time in electronic patient-reported outcomes: insights from three longitudinal clinical trials.

Patient-reported outcome measures (PROMs) are used to collect data on disease symptoms in support of clinical trial endpoints. Clinical studies can last a year or more, and the patients' adherence and response time to daily at-home questionnaires may vary significantly over time. The aim of this study was to understand patterns and changes in patients' completion of daily PROMs during longitudinal clinical studies. Data were collected from 1342 patients randomized into three respiratory clinical trials (NCT03401229, NCT03347279, and NCT03406078). PROMs were completed by patients using electronic handheld devices that collected the starting and completion times. A Bayesian generalized linear mixed-effects model was used to identify unbiased coefficients associated with PROM adherence and response time using patient, site, and calendar features as covariates. Adherence decreased over time after randomization, and the rate of decrease was higher in younger patients. The 14-day pre-randomization adherence was correlated with adherence throughout the study. Patients were also more adherent during working days compared to non-working days. Oldest patients took twice as long to complete PROMs throughout the study; however, the response time for all patients decreased during the first month of the study regardless of age. Response time increased 7days before and after the date of a scheduled clinic visit and when a patient-reported higher symptom burden. Detailed analyses of adherence and response time for daily PROMs in clinical trials can provide significant insights about trends of patient behavior in longitudinal clinical studies with high baseline adherence.

Patient-reported Symptoms of Mood, Fatigue, and Sleep Are Not Captured by Clinician-reported Outcomes in Patients with LGI1-IgG Autoimmune Encephalitis (S4.002)

Patient-reported Symptoms of Mood, Fatigue, and Sleep Are Not Captured by Clinician-reported Outcomes in Patients with LGI1-IgG Autoimmune Encephalitis (S4.002)

Randomized Trial of Remote Assessment of Patients After an Acute Coronary Syndrome

BackgroundTelemedicine programs can provide remote diagnostic information to aid clinical decisions that could optimize care and reduce unplanned readmissions post–acute coronary syndrome (ACS). ObjectivesTELE-ACS (Remote Acute Assessment of Patients With High Cardiovascular Risk Post-Acute Coronary Syndrome) is a randomized controlled trial that aims to compare a telemedicine-based approach vs standard care in patients following ACS. MethodsPatients were suitable for inclusion with at least 1 cardiovascular risk factor and presenting with ACS and were randomized (1:1) before discharge. The primary outcome was time to first readmission at 6 months. Secondary outcomes included emergency department (ED) visits, major adverse cardiovascular events, and patient-reported symptoms. The primary analysis was performed according to intention to treat. ResultsA total of 337 patients were randomized from January 2022 to April 2023, with a 3.6% drop-out rate. The mean age was 58.1 years. There was a reduced rate of readmission over 6 months (HR: 0.24; 95% CI: 0.13-0.44; P < 0.001) and ED attendance (HR: 0.59; 95% CI: 0.40-0.89) in the telemedicine arm, and fewer unplanned coronary revascularizations (3% in telemedicine arm vs 9% in standard therapy arm). The occurrence of chest pain (9% vs 24%), breathlessness (21% vs 39%), and dizziness (6% vs 18%) at 6 months was lower in the telemedicine group. ConclusionsThe TELE-ACS study has shown that a telemedicine-based approach for the management of patients following ACS was associated with a reduction in hospital readmission, ED visits, unplanned coronary revascularization, and patient-reported symptoms. (Telemedicine in High-Risk Cardiovascular Patients Post-ACS [TELE-ACS]; NCT05015634)

Quality of Life and Depression Symptoms After Therapy De-Escalation in HPV+ Oropharyngeal Squamous Cell Carcinoma

Despite interest in therapy de-escalation for survivors of human papillomavirus-mediated oropharyngeal squamous cell carcinoma (HPV-positive OPSCC), the association of de-escalated therapy with patient-reported quality of life (QoL) outcomes and burden of depressive symptoms remains unclear. To identify associations between clinicopathologic and therapeutic variables with patient-reported QoL outcomes and depression symptom burden in patients with HPV-positive OPSCC, who were enrolled in a therapy de-escalation trial. In this nonrandomized controlled, open-label, curative-intent therapy de-escalation clinical trial in adults with stage I, II, and III HPV-positive OPSCC, patients were recruited from a high-volume head and neck oncology practice. The main outcomes of this study included quantitative, patient-reported QoL and depression symptoms per well-validated inventories. Patient-reported QoL was based on Functional Assessment of Cancer Therapy-Head & Neck (FACT-HN) scores (range, 0-148; lower score indicates inferior QoL). Patient-reported depression-related symptom burden was based on Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) scores (range, 0-27; a higher score indicates a higher burden of depression symptoms). Baseline clinicopathologic and treatment variables were paired with FACT-HN and QIDS-SR scores at baseline, 3, 6, 12, 24, and 36 months. Linear mixed-effect models with a random intercept were used for each participant and fixed effects for other measures. Regression coefficients are reported with 95% CIs. A total of 95 patients were followed up for a median (IQR) of 2.2 (1.6-3.2) years. Of these, 93 patients (98%) were male with a mean (SD) age of 60.5 (8.2) years. Overall, 54 participants (57%) had a history of current or former smoking, 47 (50%) underwent curative-intent surgery (with or without adjuvant therapy), and 48 (50%) underwent primary radiotherapy (with or without chemotherapy). The median (IQR) radiotherapy dose was 60 (60-70) Gy. Five deaths and 2 recurrence events were observed (mean [SD] recurrence interval, 1.4 [1.5] years). A higher radiotherapy dose was the only modifiable factor associated with inferior patient-reported QoL (lower FACT-HN) (coefficient, -0.66 [95% CI, -1.09 to -0.23]) and greater burden of depression-related symptoms (higher QIDS-SR) (coefficient, 0.11 [95% CI, 0.04-0.19]). With the 70-Gy dose as reference, improvements in FACT-HN and QIDS-SR scores were identified when patients received 51 to 60 Gy (coefficient, 12.75 [95% CI, 4.58-20.92] and -2.17 [-3.49 to -0.85], respectively) and 50 Gy or lower (coefficient, 15.03 [4.36-25.69] and -2.80 [-4.55 to -1.04]). In this nonrandomized controlled, open-label, curative-intent therapy de-escalation trial, a higher radiotherapy dose was associated with inferior patient-reported QoL and a greater burden of depression-related symptoms. This suggests opportunities for improved QoL outcomes and reduced depression symptom burden with a reduction in radiotherapy dose. ClinicalTrials.gov Identifier: NCT04638465.

Muscle Tension Dysphagia: An Expanded Investigation of Clinical Presentations and Swallowing Kinematics.

This study retrospectively examined patient-reported symptoms, quality of life, and swallowing kinematics in individuals with presumed muscle tension dysphagia (MTDg). Twenty-six individuals met the inclusion criteria. Data were gathered from patient-reported outcome measures (PROs), symptomology, clinician reports of palpation, and hyolaryngeal and hyoid movements measured on a 20-ml thin liquid bolus during videofluoroscopic swallowing studies. All PROs were outside of typical limits, except for the Voice Handicap Index-10. Mean hyoid excursion was 1.52 cm (SD = 0.46, range: 0.76-2.43), and hyolaryngeal excursion was 0.77 cm (SD = 0.44, range: -0.42-1.68). A minority of participants (4%-19%) demonstrated atypical hyoid and/or hyolaryngeal excursion compared to the available normative reference value sets. Individuals demonstrated abnormalities in the clinical evaluation of the areas of palpation and reported perilaryngeal discomfort and symptoms of laryngeal hyperresponsiveness, with a negative impact on their quality of life across various PROs. Atypical hyoid and/or hyolaryngeal excursion during swallowing was rare when compared to available normative reference values. The clinical evaluation of MTDg may be enhanced by including components related to muscle tension and laryngeal hyperresponsiveness in order to differentiate MTDg from idiopathic functional dysphagia and lead the patient to the otolaryngology/speech-language pathology clinic for intervention and management.

Qualitative study exploring the design of a patient-reported symptom-based risk stratification system for suspected head and neck cancer referrals: protocol for work packages 1 and 2 within the EVEREST-HN programme

IntroductionBetween 2009/2010 and 2019/2020, England witnessed an increase in suspected head and neck cancer (sHNC) referrals from 140 to 404 patients per 100 000 population. 1 in 10 patients are...

Depressive Symptoms, Systemic Inflammation, and Survival Among Patients With Head and Neck Cancer

Patients with head and neck cancer experience high rates of depression. Depression and systemic inflammation have been found to be associated in numerous cancer types, often independently from disease status. Depression-related inflammation may elevate the risks for poor tumor response to treatment and early mortality, and comprises a mechanism by which depression is associated with survival in head and neck cancer. To assess mediation pathways incorporating pretreatment depressive symptoms, pretreatment inflammation, and tumor response posttreatment on overall survival among patients with head and neck cancer. This was a prospective observational cohort study of patients with head and neck cancer treated in a single multidisciplinary head and neck cancer clinic from May 10, 2013, to December 30, 2019, and followed up for 2 years. Data analysis was performed from June 29, 2022, to June 23, 2023. Patient-reported depressive symptoms using the Patient Health Questionnaire-9 item (PHQ-9) at treatment planning; pretreatment hematology workup for systemic inflammation index (SII) score; and clinical data review for tumor response (complete vs incomplete) and overall survival. Two-year overall survival. The total study cohort included 394 patients (mean [SD] age, 62.5 [11.5] years; 277 [70.3%] males) with head and neck cancer. Among 285 patients (72.3%) who scored below the clinical cutoff for depression on the PHQ-9, depressive symptoms were significantly associated with inflammation (partial r, 0.168; 95% CI, 0.007-0.038). In addition, both depression and inflammation were associated with early mortality (PHQ-9: hazard ratio [HR], 1.04; 95% CI, 1.02-1.07; SII: HR, 1.36; 95% CI, 1.08-1.71). The depression-survival association was fully mediated by inflammation (HR, 1.28; 95% CI, 1.00-1.64). Depressive symptoms were also associated with poorer tumor response (odds ratio, 1.05; 95% CI, 1.01-1.08), and the depression-survival association was partially mediated by tumor response (HR, 9.44; 95% CI, 6.23-14.32). Systemic inflammation was not associated with tumor response. In this cohort study, systemic inflammation emerged as a novel candidate mechanism of the association of depression with mortality. Tumor response partially mediated effects of depression on mortality, replicating prior work. Thus, depression stands out as a highly feasible target for renewed clinical attention. Even mild symptoms of depression during the treatment-planning phase may be associated with higher systemic inflammation in addition to poorer tumor response to treatment and survival outcomes; therefore, depression should be clinically addressed.

Patient-reported symptoms before adjuvant locoregional radiotherapy for breast cancer: triple-negative histology impacts the symptom burden.

Multimodal breast cancer treatment may cause side effects reflected in patient-reported outcomes and/or symptom scores at the time of treatment planning for adjuvant radiotherapy. In our department, all patients have been assessed with the Edmonton Symptom Assessment System (ESAS; aquestionnaire addressing 11major symptoms and wellbeing on anumeric scale of 0-10) at the time of treatment planning since 2016. In this study, we analyzed ESAS symptom severity before locoregional radiotherapy. Retrospective review of 132 patients treated between 2016 and 2021 (all comers in breast-conserving or post-mastectomy settings, different radiotherapy fractionations) was performed. All ESAS items and the ESAS point sum were analyzed to identify subgroups with higher symptom burden and thus need for additional care measures. The biggest patient-reported issues were fatigue, pain, and sleep problems. Patients with triple negative breast cancer reported ahigher symptom burden (mean 30 versus20, p = 0.038). Patients assigned to adjuvant endocrine therapy had the lowest point sum (mean18), followed by those on Her-2-targeting agents without chemotherapy (mean19), those on chemotherapy with or without other drugs (mean26), and those without systemic therapy (mean41), p = 0.007. Those with pathologic complete response after neoadjuvant treatment had significantly lower anxiety scores (mean 0.7 versus1.8, p = 0.03) and atrend towards lower depression scores, p = 0.09. Different surgical strategies, age, and body mass index did not impact on ESAS scores, while the type of adjuvant systemic therapy did. The effect of previous neoadjuvant treatment and unfavorable tumor biology (triple negative) emerged as important factors associated with symptom burden, albeit in different domains. ESAS data may facilitate identification of patients who should be considered for additional supportive measures to alleviate specific symptoms.

Abstract 6384: DNA methylation based aging biomarkers mediate the association between patient-reported symptoms and all-cause late-mortality: A report from the St. Jude Lifetime Cohort

Abstract Background: Long-term survivors of childhood cancer experience high rates of patient-reported symptoms and evidence for accelerated molecular aging. Both are established to increase the risk for late-mortality (&amp;gt;5 years from cancer diagnosis). We aim to investigate if accelerated molecular aging mediates the association between symptoms and all-cause late-mortality. Methods: DNA methylation (DNAm)-based aging biomarkers were derived from the DNAm Age Calculator, including epigenetic age acceleration (EAA) using multiple clocks (e.g., GrimAge and PhenoAge) and other DNAm-predicted biomarkers (e.g., DNAmB2M: beta-2-microglobulin, DNAmTL: telomere length) adjusted for age and standardized. Survivors self-reported the presence of 10 symptom domains (cardiac, pulmonary, sensory, motor/movement, nausea, pain, fatigue, memory, anxiety, and depression) that were aggregated into a total symptom burden score. Multiple linear regression tested the association between each aging biomarker and symptom prevalence, adjusting for the age of symptom survey, sex, and cancer treatment exposures. Cox regression tested the association of each aging biomarker or symptom domain with mortality. Aging biomarkers mediation for the symptom-mortality association was assessed by using the Accelerated Failure Time model and the mediation R package. False discovery rate was controlled for multiple testing. Results: Among 2,206 survivors (47% males) who had DNAm measured on (52%) or after the survey, the median duration from the symptom survey to DNA sampling were 0.48 years (IQR: 0.09-4.27 years). EAA_GrimAge was the aging biomarker most closely associated with total symptom burden (beta [95%CI] = 0.576 [0.455, 0.697] years, P=2.89×10-18) and eight of ten domain-specific symptoms except for motor/movement and memory. Seven aging biomarkers (e.g., DNAmB2M: 1.91 [1.48, 2.48], P=1.87×10-5; EAA_GrimAge: HR [95%CI] = 1.17 [1.09, 1.26], P=3.1×10-4 ) and five symptom domains (e.g., pulmonary: 2.54 [1.44, 4.49], P=0.004; cardiac: 2.25[1.28, 3.97], P=0.01; total symptom burden: 1.47 [1.18, 1.82], P=0.0019) were associated with mortality risk. EAA (e.g., EAA_GrimAge) mediated the association between symptoms (cardiac: % mediation =0.13 [0.044, 0.379], P=0.008; pulmonary: 0.186 [0.075, 0.486], P=0.008; and total symptoms: 0.206 [0.078, 0.503], P=0.012) and late mortality. In addition, the association between symptoms and mortality was mediated by DNAmB2M and DNAmTL (e.g., pulmonary: 0.152 [0.046, 0.378], P=0.008; 0.12 [0.031, 0.373], P=0.021). Conclusions: EAA, DNAmB2M and DNAmTL mediated the association between the presence of specific symptom domains and late-mortality, suggesting that accelerated molecular aging may be an underlying biological pathway explaining the associations between symptom burden and mortality. Citation Format: Qian Li, Yue Pan, Xijun Zhang, Noel-Marie Plonski, g Chen, Qian Dong, Kyla Shelton, John Easton, Heather Mulder, Jinghui Zhang, Geoffrey Neale, Emily Walker, Deo Kumar Srivastava, Greg T. Armstrong, Kirsten Ness, I-Chan Huang, Zhaoming Wang. DNA methylation based aging biomarkers mediate the association between patient-reported symptoms and all-cause late-mortality: A report from the St. Jude Lifetime Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6384.

Abstract 7448: Serum IL-10 is associated with neurologic symptoms and interference in primary brain tumor patients

Abstract Background: Primary brain tumors (PBT) are associated with neurocognitive symptoms as a direct result of the tumor or its treatment. IDH-mutant gliomas are associated with longer survival, but with higher incidence of seizures and neurocognitive symptoms.​ Correlations between cytokines and neuroinflammation have been reported in other structural brain lesions but have not been evaluated in PBT. Here, we investigate elevated peripheral blood levels of proteins (cytokine levels) in a cross-sectional cohort (n=47) of adult, IDH-mutant PBT patients enrolled in a natural history study (NCT02851706, PI: T. Armstrong) versus healthy subjects (n=32) and the correlations between cytokine levels and patient-reported outcomes (PROs). Methods: Patient-reported symptoms and activity-related interference were collected via the MD Anderson Symptom Inventory-Brain Tumor at study entry. Serum samples were stored at -80°C for batch processing and used for biomarker analysis. Ten cytokines (interleukin-1β [IL-1β], IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ [IFN-γ], and tumor necrosis factor-α [TNF-α]) were quantified in duplicate using an immunoassay (V-Plex/Proinflammatory, Meso Scale Discovery [MSD], Rockville, MD). Lab personnel were blinded to diagnosis and patient clinical status. Mean concentration (pg/mL) levels or ‘present or not detectable’ values were used. Descriptive statistics, Mann-Whitney tests, and Spearman correlations were conducted at p &amp;lt;0.05. Results: The patient sample was mostly male (62%), White (70%), employed (64%), had no prior recurrence (62%), high grade (3-4) tumors (70%), and an average age at diagnosis of 36 years (SD: 9; median: 34; range: 20-53). The healthy subject sample was mostly female (53%) and White (72%), with an average age of 46 years (SD: 19; median: 50; range: 19-78). Five cytokines (IFN-γ, IL-6, IL-8, IL-10, and TNF-α) were detectable in patients and healthy subjects with levels of IL-6, IL-10, and TNF-α higher in patients than healthy subjects. Serum levels of IL-10 (mean rank=50.7 vs 24.3, p&amp;lt;0.001) and TNF-α (mean rank=50.6 vs 24.2, p&amp;lt;0.001) were higher in PBT patients when compared to healthy subjects. Only IL-10, but not other cytokines, positively correlated with severity of patient-reported symptoms [pain (r=0.290, p=0.048), numbness/tingling (r=0.302, p=0.039)], and activity-related interference, including work (r=0.323, p=0.027), and walking (r=0.402, p=0.005). Conclusions: Higher IL-10 levels and detection differences in other cytokines, may indicate a reduction in immune-mediating processes and heightening inflammation in patients. Future analysis will include replication of this work in a larger cohort across PBT types to evaluate risk, explore mechanisms, and associations with treatment types. Citation Format: Kaitlynn A. Slattery, Michelle L. Wright, Dhaivat Raval, Emory Hsieh, McKenzie C. Kauss, Terri S. Armstrong, Tito R. Mendoza, Vivian A. Guedes. Serum IL-10 is associated with neurologic symptoms and interference in primary brain tumor patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7448.

Abstract 819: Feasibility of patient-centered home care (PCHC) to reduce disparities in high-risk black men with advanced prostate cancer

Abstract The objective of our study is to evaluate the feasibility, acceptance, and impact of patient-centered home care (PCHC) on patient reported outcomes (PROs) and health-related quality of life (HQoL) of black men with advanced prostate cancer (CaP). Meeting patients where they are and offering treatment in or closer to their homes reduce psychological distress and increase treatment compliance, especially for disadvantaged patients in rural areas, those on low incomes, with poor access to transport, elderly and people with disabilities. In 2023, Mayo Clinic has developed the Cancer Care Beyond Walls (CCBW) program, a cancer care delivery model that integrates virtual with in facility treatment and provides a package of care to support administration of cancer-directed therapy (chemotherapy, immunotherapy, hormonal therapy) and/or supportive care in the patients’ homes. Our study will assess if patients and families are comfortable with cancer therapy at home, what factors influences their decision, and use this data to inform our understanding of the proportion of the black men with advanced CaP who would be willing to receive and would benefit from this level of care at home. Patients with advanced CaP from our practice requiring active anti-cancer therapy are administered a brief questionnaire regarding preference for location of therapy at the infusion center or in the home, with perceived difficulties and advantages of each approach. A focus group session with prostate cancer survivor advocates is also conducted to capture patients’ thoughts, feelings, attitudes, and questions towards cancer treatments being administered at home versus a hospital setting. In addition, we are conducting an observational study of 20 patients with advanced prostate cancer receiving supportive care/symptom management and/or anti-cancer therapy in the home as part of the Mayo Clinic CCBW Program to assess the safety of cancer directed therapy when administered at home by a home health provider with remote patient monitoring and command center support, and establish the impact of home cancer treatment administration on patient-reported function and global health/quality of life, patient-reported symptoms, clinical outcomes, and cost of care. Successful completion of the project will deliver data on patient understanding and acceptability of cancer care at home, strategies for overcoming barriers to care for underserved communities, and the foundation from which we discover, translate and apply new knowledge in administering personalized care to vulnerable populations. Citation Format: Roxana S. Dronca, Folakemi Odedina, Che Ngufor, Kimlin Ashing, Ernest Kaninjing, Solomon Rotimi. Feasibility of patient-centered home care (PCHC) to reduce disparities in high-risk black men with advanced prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 819.

Abstract 7454: Cognitive function in older breast cancer survivors after chemotherapy

Abstract Background: In the United States, over 60% of breast cancer survivors are 65 years and older; however, little is known about patient-reported symptoms and the effect that cancer treatments could have on survivors years after their primary treatment and diagnosis. This study evaluated perceived cognitive function in older breast cancer survivors and whether prior chemotherapy was associated with cognitive outcomes. Methods: Breast cancer patients aged 65 years and older, diagnosed 2012-2013, with local and regional stage disease, were identified through the linked Texas Cancer Registry-Medicare dataset (TCR). Survivors were mailed a survey to assess their cognitive function through the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog V3) instrument (section G of the survey). The survey also collected demographic and clinical data and was collected between April 2018 and October 2019. Utilizing the data from the self-administered questionnaires, TCR, and Medicare claims, the cognitive function and quality of life among elderly patients were evaluated to assess whether prior chemotherapy and/or endocrine therapy impacts long-term health. A linear regression model was used to examine the significance of receiving chemotherapy to FACT-Cog V3 primary score while controlling for respondent sociodemographic and clinical variables. Results: Of 4,448 eligible patients, 1,954 (43.9% response rate) responded to section G. Of these, 1,065 respondents completed all 4 sections, 37 questions. Eighty of those 1065 respondents self-reported disease recurrence which excluded them from the analyses in order to avoid biases, leaving a total of 985 cases for this study. Median time from diagnosis to survey completion was 68 months (IQR 62-73). Receipt of chemotherapy was associated with a slightly lower FACT-Cog score. In total, those with chemotherapy scored, on average, 105.6 (SD 21.2) while those without scored 107.1 (SD 22.3). The largest difference in mean scores is attributed to the Perceived Cognitive Impairment subsection (scored from 0-72) where those with chemotherapy scored, on average, 57.2 (SD 13.8) and those without scored 58.7 (SD 14.0). Responsible Conduct Of Research: We need to ensure that the privacy of our patients will be protected when using their information from the surveys. Conclusion: Adjuvant chemotherapy was associated with more self-reported cognitive impairment in older breast cancer survivors, even 5-6 years after diagnosis. However, the difference between patients who received chemotherapy versus those who did not was modest, suggesting limited clinical significance. Further research is needed to determine the long-term impact of cancer treatments, particularly in older cancer survivors. Citation Format: Rachel Kim, Kai-Ping Liao, Susan Peterson, Daria Zorzi, Liang Li, Mariana Chavez MacGregor, Sharon Giordano. Cognitive function in older breast cancer survivors after chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7454.

Abstract 126: Effect of active cytomegalovirus infection on symptoms of fatigue, cancer-related cognitive impairment, and peripheral neuropathy in ovarian cancer survivors

Abstract Background: Fatigue, cancer-related cognitive impairment (CRCI) and neuropathy are among the most common and distressing side effects reported by individuals treated with chemotherapy for ovarian cancer. Cytomegalovirus (CMV) is a highly prevalent herpes virus infection worldwide, affects inflammation and immune function, and can reactivate with treatment for cancer. This study aimed to explore the associations between active CMV infection and patient-reported symptoms among ovarian cancer survivors who have completed front-line chemotherapy. Methods: We conducted a cross-sectional study among individuals with a history of a diagnosis of ovarian cancer, primary peritoneal cancer, or fallopian tube cancer from academic and community cancer clinics in Minnesota at any time point after completion of front-line chemotherapy. Participants completed a one-time survey and provided a blood sample. The exposure of interest was plasma CMV DNA level measured using digital PCR, with ≥100 copies/mL of plasma considered active infection (CMV+). We measured symptoms of fatigue (Fatigue Symptom Inventory), CRCI (PROMIS Cognitive Function 8a) and peripheral neuropathy (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity) using validated self-reported measures. Data were analyzed using descriptive statistics and compared by active CMV infection status (CMV+ vs. CMV-) in the full group and by treatment status (receipt of chemotherapy within 30 days prior to data collection) using t-tests. Results: A total of 160 participants were analyzed. Participants were median of 64.0 years old and 2.3 years from initial diagnosis. Most (75.2%) had advanced stage disease, 43.8% had experienced at least one recurrence, and 40.0% received chemotherapy within 30 days prior to participation. Overall, 40.0% were CMV+, with 40.6% CMV+ among those who received chemotherapy within 30 days and 39.6% CMV+ among those who had not. Participants who were CMV+, compared to those who were CMV-, had overall worse symptoms, with greater symptoms of neuropathy in the full group (11.9±9.2 vs. 9.1±7.8, p=0.04) and particularly greater symptoms of CRCI among those who had recently received chemotherapy (29.2±7.4 vs. 33.2±6.7, p=0.03). Conclusion: We identified that active CMV infection is common in this survivor population and found that worse symptoms of neuropathy and CRCI are associated with CMV+ status. These results are consistent with studies among other immune-compromised populations, and with further validation, provide a potential therapeutic path for reducing these symptoms. Citation Format: Xuan Li, Katherine Brown, Kate Honeyfield, Devon Hunter-Schlichting, Morgan Gruner, Deanna Teoh, Melissa Geller, Heather Nelson, Rachel I. Vogel. Effect of active cytomegalovirus infection on symptoms of fatigue, cancer-related cognitive impairment, and peripheral neuropathy in ovarian cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 126.

Effect of CYP2D6 genetic variation on patient-reported symptom improvement and side effects among children and adolescents treated with amphetamines.

Amphetamine-based medications are recommended as a first-line pharmacotherapy for the treatment of attention-deficit/hyperactivity disorder in children and adolescents. However, the efficacy and tolerability of these medications vary across individuals, which could be related to interindividual differences in amphetamine metabolism. This study examined if genotype-predicted phenotypes of the cytochrome P450 isozyme CYP2D6 were associated with self-reported side effects and symptom improvement in youth treated with amphetamines. Two hundred fourteen participants aged 6-24 who had a history of past or current amphetamine treatment were enrolled from Western Canada. Amphetamine dose and duration information was collected from the participants along with questions regarding adherence, concomitant medications, symptom improvement and side effects. DNA was extracted from saliva samples and genotyped for CYP2D6 . Binomial logistic regression models were used to determine the effect of CYP2D6 metabolizer phenotype with and without correction for phenoconversion on self-reported symptom improvement and side effects. Genotype-predicted CYP2D6 poor metabolizers had significantly higher odds of reporting symptom improvement when compared to intermediate metabolizers (OR = 3.67, 95% CI = 1.15-11.7, P = 0.029) after correction for phenoconversion and adjusting for sex, age, dose, duration, and adherence. There was no association between CYP2D6 metabolizer phenotype and self-reported side effects. Our findings indicate that phenoconverted and genotype-predicted CYP2D6 poor metabolizer phenotype is significantly associated with higher odds of symptom improvement in children and adolescents treated with amphetamine. If replicated, these results could inform the development of future dosing guidelines for amphetamine treatment in children and adolescents.

A comparison of the prevalence of dry mouth and other symptoms using two different versions of the Edmonton Symptom Assessment System on an inpatient palliative care unit

BackgroundSymptom assessment is key to effective symptom management and palliative care for patients with advanced cancer. Symptom prevalence and severity estimates vary widely, possibly dependent on the assessment tool used. Are symptoms specifically asked about or must the patients add them as additional symptoms? This study compared the prevalence and severity of patient-reported symptoms in two different versions of a multi-symptom assessment tool. In one version, three symptoms dry mouth, constipation, sleep problems were among those systematically assessed, while in the other, these symptoms had to be added as an “Other problem”.MethodsThis retrospective cross-sectional study included adult patients with advanced cancer at an inpatient palliative care unit. Data were collected from two versions of the Edmonton Symptom Assessment System (ESAS): modified (ESAS-m) listed 11 symptoms and revised (ESAS-r) listed 9 and allowed patients to add one “Other problem”. Seven similar symptoms were listed in both versions.ResultsIn 2013, 184 patients completed ESAS-m, and in 2017, 156 completed ESAS-r. Prevalence and severity of symptoms listed in both versions did not differ. In ESAS-m, 83% reported dry mouth, 73% constipation, and 71% sleep problems, but on ESAS-r, these symptoms were reported by only 3%, 15% and < 1%, respectively. Although ESAS-r severity scores for these three symptoms were higher than on ESAS-m, differences did not reach statistical significance.ConclusionWe identified significant differences in patient symptom reporting based on whether symptoms like dry mouth, obstipation and sleep problems were specifically assessed or had to be added by patients as an “Other problem”.