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BACKGROUND: Interindividual variability in oncology patients symptom experiences poses significant challenges in prioritizing symptoms for targeted intervention(s). In this study, computational approaches were used to unbiasedly characterize the heterogeneity of the symptom experience of oncology patients to elucidate symptom patterns and drivers of symptom burden. METHODS: Severity ratings for 32 symptoms on the Memorial Symptom Assessment Scale from 3088 oncology patients were analyzed. Gaussian Graphical Model symptom networks were constructed for the entire cohort and patient subgroups identified through unsupervised clustering of symptom co-severity patterns. Network characteristics were analyzed and compared using permutation-based statistical tests. Differences in demographic and clinical characteristics between subgroups were assessed using multinomial logistic regression. RESULTS: Network analysis of the entire cohort revealed three symptom clusters: constitutional, gastrointestinal-epithelial, and psychological. Lack of energy was identified as central to the network which suggests that it plays a pivotal role in patients overall symptom experience. Unsupervised clustering of patients based on shared symptom co-severity patterns identified six patient subgroups with distinct symptom patterns and demographic and clinical characteristics. The centrality of individual symptoms across the subgroup networks differed which suggests that different symptoms need to be prioritized for treatment within each subgroup. Age, treatment status, and performance status were the strongest determinants of subgroup membership. CONCLUSIONS: Computational approaches that combine unbiased stratification of patients and in-depth modeling of symptom relationships can capture the heterogeneity in patients symptom experiences. When validated, the core symptoms for each of the subgroups and the associated clinical determinants may inform precision-based symptom management.

PurposeOne plausible mechanistic hypothesis is the potential contribution of inflammatory mechanisms to shortness of breath. This study was aimed to evaluate for associations between the occurrence of shortness of breath and perturbations in inflammatory pathways.MethodsPatients with cancer reported the occurrence of shortness of breath six times over two cycles of chemotherapy. Latent class analysis was used to identify subgroups of patients with distinct shortness of breath occurrence profiles (i.e., none (70.5%), decreasing (8.2%), increasing (7.8%), high (13.5%)). Using an extreme phenotype approach, whole transcriptome differential gene expression and pathway impact analyses were performed to evaluate for perturbed signaling pathways associated with shortness of breath between the none and high classes. Two independent samples (RNA-sequencing (n = 293) and microarray (n = 295) methodologies) were evaluated. Fisher's combined probability method was used to combine these results to obtain a global test of the null hypothesis. In addition, an unweighted knowledge network was created using the specific pathway maps to evaluate for interconnections among these pathways.ResultsTwenty-nine Kyoto Encyclopedia of Genes and Genomes inflammatory signaling pathways were perturbed. The mitogen-activated protein kinase signaling pathway node had the highest closeness, betweenness, and degree scores. In addition, five common respiratory disease-related pathways, that may share mechanisms with cancer-related shortness of breath, were perturbed.ConclusionsFindings provide preliminary support for the hypothesis that inflammation contribute to the occurrence of shortness of breath in patients with cancer. In addition, the mechanisms that underlie shortness of breath in oncology patients may be similar to other respiratory diseases.

BACKGROUND: By 2035, the number of newly diagnosed cancer cases will double and over 50% will be in older adults. Given this rapidly growing demographic, a need exists to understand how age influences oncology patients symptom burden. The study purposes were to evaluate for differences in the occurrence, severity, and distress of 38 symptoms in younger (

BACKGROUND: Shortness of breath occurs in 10%-70% of oncology patients. Very little is known about interindividual variability in its severity and distress and associated risk factors. Using latent profile analyses (LPAs), purpose was to identify subgroups of patients with distinct severity and distress profiles for shortness of breath as single symptom dimensions. In addition, a joint LPA was done using patients severity AND distress ratings. For each of the three LPAs, differences among the shortness of breath classes in demographic, clinical, symptom, stress, and resilience characteristics were evaluated. METHODS: Patients completed ratings of severity and distress from shortness of breath a total of six times over two cycles of chemotherapy. All of the other measures were completed at enrollment (i.e., prior to the second or third cycle of chemotherapy). Separate LPAs were done using ratings of severity and distress, as well as a joint analysis using severity AND distress ratings. Differences among the latent classes were evaluated using parametric and nonparametric tests. RESULTS: For severity, two classes were identified (Slight to Moderate [91.6%] and Moderate to Severe [8.4%]). For distress, two classes were identified (A Little Bit to Somewhat [83.9%] and Somewhat to Quite a Bit [16.1%]). For the joint LPA, two classes were identified (Lower Severity and Distress [79.9%] and Higher Severity and Distress [20.1%]). While distinct risk factors were associated with each of the LPAs, across the three LPAs, the common risk factors associated with membership in the worse class included: a past or current history of smoking, poorer functional status, and higher comorbidity burden. In addition, these patients had a higher symptom burden and higher levels of cancer-specific stress. CONCLUSIONS: Clinicians can use the information provided in this study to identify high-risk patients and develop individualized interventions.

ObjectivePatients with gynecologic cancers experience a very high symptom burden that has a negative impact on their quality of life. This systematic review aims to identify the common co-occurring symptoms, the prevalence of common symptoms, common instruments used to measure symptoms, associated risk factors, and the symptom burden in patients with gynecologic cancers.Data sourcesA search of four databases (ie, PubMed, Embase, Web of Science, and CINAHL) was done from January 1, 2012, through September 5, 2022. A qualitative synthesis of the extant literature was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA 2020).ConclusionA total of 118 studies met the prespecified inclusion criteria. Ninety-six symptoms were assessed across these studies. The top six symptoms and their grand mean prevalence rates were lack of energy (64.4%), fatigue (62.1%), abdominal pain (53.3%), depression (52.6%), concentration dysfunction (52.0%), and drowsiness (51.9%). Numerous methodologic challenges were evident across studies. Future research needs to develop a disease-specific symptom assessment measure, evaluate for risk factors associated with a higher symptom burden, and determine the impact of multiple symptoms on patient outcomes.Implication for nursing practiceThe results are relevant for oncology clinicians to assess patients with gynecologic cancers for the presence of common symptoms and risk factors for higher symptom burden in the patients and to offer effective management interventions.

The persistence of inflammatory and neuropathic pain is poorly understood. We investigated a novel therapeutic paradigm by targeting gene networks that sustain or reverse persistent pain states. Our prior observations found that Sp1-like transcription factors drive the expression of TRPV1, a pain receptor, that is blocked in vitro by mithramycin A (MTM), an inhibitor of Sp1-like factors. Here, we investigate the ability of MTM to reverse in vivo models of inflammatory and chemotherapy-induced peripheral neuropathy (CIPN) pain and explore MTMs underlying mechanisms. Mithramycin reversed inflammatory heat hyperalgesia induced by complete Freund adjuvant and cisplatin-induced heat and mechanical hypersensitivity. In addition, MTM reversed both short-term and long-term (1 month) oxaliplatin-induced mechanical and cold hypersensitivity, without the rescue of intraepidermal nerve fiber loss. Mithramycin reversed oxaliplatin-induced cold hypersensitivity and oxaliplatin-induced TRPM8 overexpression in dorsal root ganglion (DRG). Evidence across multiple transcriptomic profiling approaches suggest that MTM reverses inflammatory and neuropathic pain through broad transcriptional and alternative splicing regulatory actions. Mithramycin-dependent changes in gene expression following oxaliplatin treatment were largely opposite to and rarely overlapped with changes in gene expression induced by oxaliplatin alone. Notably, RNAseq analysis revealed MTM rescue of oxaliplatin-induced dysregulation of mitochondrial electron transport chain genes that correlated with in vivo reversal of excess reactive oxygen species in DRG neurons. This finding suggests that the mechanism(s) driving persistent pain states such as CIPN are not fixed but are sustained by ongoing modifiable transcription-dependent processes.

PurposeEvaluate for perturbed signaling pathways associated with subgroups of patients with low versus high levels of state anxiety. These pathways were compared to the pathways identified across eight network pharmacology studies of the anxiolytic effect(s) of a variety of compounds.MethodsAdult outpatients had a diagnosis of breast, gastrointestinal, gynecological, or lung cancer; had received chemotherapy within the preceding four weeks; and were scheduled to receive at least two additional cycles of chemotherapy. Latent profile analysis was used to identify subgroups of patients with distinct anxiety profiles based on Spielberger State Anxiety Inventory scores that were obtained six times over two cycles of chemotherapy. Blood samples were processed using RNA sequencing (i.e., RNA-seq sample, n = 244) and microarray (i.e., microarray sample; n = 256) technologies. Pathway perturbations were assessed using pathway impact analysis. Fisher's combined probability method was used to combine test results using a false discovery rate of 0.01.ResultsIn the RNA-seq sample, 62.3% and 37.7% of the patients were in the low- and high-anxiety classes, respectively. In the microarray sample, 61.3% and 38.7% were in the low and high-anxiety classes, respectively. Forty-one perturbed signaling pathways were identified. Eight of these pathways were common to those identified in the network pharmacology studies.ConclusionsFindings increase our knowledge of the molecular mechanisms that underlie anxiety in patients receiving chemotherapy. This study provides initial insights into how anxiety in patients with cancer may share common mechanisms with anxiety in patients with other clinical conditions.

While the epidemiological literature recognizes associations between chronic non-cancer pain (CNCP), opioid use disorder (OUD), and interpersonal trauma stemming from physical, emotional, sexual abuse or neglect, the complex etiologies and interplay between interpersonal and structural traumas in CNCP populations are under-examined. Research has documented the relationship between experiencing multiple adverse childhood experiences (ACEs) and the likelihood of developing an OUD as an adult. However, the ACEs framework is criticized for failing to name the social and structural contexts that shape ACE vulnerabilities in families. Social scientific theory and ethnographic methods offer useful approaches to explore how interpersonally- and structurally-produced traumas inform the experiences of co-occurring CNCP, substance use, and mental health. We report findings from a qualitative and ethnographic longitudinal cohort study of patients with CNCP (n = 48) who received care in safety-net settings and their primary care providers (n = 23). We conducted semi-structured interviews and clinical and home-based participant observation from 2018 to 2020. Here we focus our analyses on how patients and providers explained and situated the role of patient trauma in the larger clinical context of reductions in opioid prescribing to highlight the political landscape of the United States opioid overdose crisis and its impact on clinical interactions. Findings reveal the disproportionate burden structurally-produced, racialized trauma places on CNCP, substance use and mental health symptoms that shapes patients’ embodied experiences of pain and substance use, as well as their emotional experiences with their providers. Experiences of trauma impacted clinical care trajectories, yet providers and patients expressed limited options for redress. We argue for an adaptation of trauma-informed care approaches that contextualize the structural determinants of trauma and their interplay with interpersonal experiences to improve clinical care outcomes.

BackgroundAnxiety and sleep disturbance are frequent symptoms during chemotherapy.ObjectivesPurposes were to identify subgroups of oncology outpatients with distinct joint anxiety and sleep disturbance profiles, as well as evaluate for differences in demographic and clinical characteristics, sleep disturbance characteristics, severity of common symptoms, and quality-of-life outcomes among these subgroups.MethodsOncology outpatients (n = 1331) completed self-report measures of anxiety and sleep disturbance 6 times over 2 chemotherapy cycles. Latent profile analysis was done to identify subgroups of patients with distinct joint anxiety and sleep disturbance profiles.ResultsThree profiles were identified (ie, no anxiety and low sleep disturbance (59.7%), moderate anxiety and high sleep disturbance (32.5%), high anxiety and very high sleep disturbance (7.8%)). Compared with the no anxiety and low sleep disturbance class, the other 2 classes were younger; less likely to be married; had a lower annual household income; and had childcare responsibilities. Patients in the 2 worse profiles had problems with both sleep initiation and maintenance. These patients reported higher levels of depressive symptoms, trait and state anxiety, and evening fatigue, as well as lower levels of morning and evening energy, cognitive function, and poorer quality of life.ConclusionsMore than 40% of patients had moderate or high levels of anxiety and high or very high levels of sleep disturbance. Modifiable risk factors associated with these profiles may be used to develop targeted interventions for 1 or both symptoms.Implications for practiceClinicians need to assess for the co-occurrence of anxiety and sleep disturbance.

OBJECTIVES: Among four classes of patients with distinct shortness of breath profiles, evaluate for differences in levels of global, cancer-specific, and cumulative life stress, as well as resilience; evaluate for differences in the occurrence rates for various stressful life events, and evaluate for differences in the severity of common co-occurring symptoms. DATA SOURCES: Outpatients (N = 1338) completed questionnaires six times over two cycles of chemotherapy. The occurrence of shortness of breath was assessed using the Memorial Symptom Assessment Scale. Latent class analysis was used to identify subgroups of patients with distinct shortness of breath profiles. Differences among the classes were evaluated using parametric and nonparametric tests. CONCLUSION: Shortness of breath classes were labeled based on their distinct occurrence trajectories: None (70.5%), Decreasing (8.2%), Increasing (7.8%), and High (13.5%). Compared to None class, Decreasing and High classes had higher global and cancer-specific stress scores. The High class reported higher occurrence rates for several adverse childhood experiences. Compared to None class, Decreasing and High classes had higher depression, anxiety, and morning fatigue scores and lower morning energy and cognitive function scores. IMPLICATIONS FOR NURSING PRACTICE: Given the additive or synergistic relationships between stress, co-occurring symptoms, and shortness of breath, multimodal interventions that include stress management, exercise training, and/or symptom management may decrease shortness of breath in oncology patients.

A workshop titled Beyond the Symptom: The Biology of Fatigue was held virtually September 27-28, 2021. It was jointly organized by the Sleep Research Society and the Neurobiology of Fatigue Working Group of the NIH Blueprint Neuroscience Research Program. For access to the presentations and video recordings, see: https://neuroscienceblueprint.nih.gov/about/event/beyond-symptom-biology-fatigue. The goals of this workshop were to bring together clinicians and scientists who use a variety of research approaches to understand fatigue in multiple conditions and to identify key gaps in our understanding of the biology of fatigue. This workshop summary distills key issues discussed in this workshop and provides a list of promising directions for future research on this topic. We do not attempt to provide a comprehensive review of the state of our understanding of fatigue, nor to provide a comprehensive reprise of the many excellent presentations. Rather, our goal is to highlight key advances and to focus on questions and future approaches to answering them.

ObjectivesLittle is known about hearing loss and tinnitus associated with neurotoxic chemotherapy. Study evaluated for differences in occurrence rates and effects of hearing loss and tinnitus in survivors who received a platinum alone, a taxane alone or a platinum and taxane containing regimen.MethodsTotal of 273 survivors with breast, gastrointestinal, gynaecological or lung cancer completed self-report measures of hearing loss and tinnitus and had an audiometric assessment that obtained pure tone air conduction thresholds bilaterally at frequencies of between 0.25 kHz to 16.0 kHz. To adjust for age-related and gender-related changes in hearing, each survivor's audiogram was evaluated using the National Health and Nutrition Examination Survey-modified Occupational Safety and Health Administration standards. Survivor was classified as having hearing loss if at any frequency they scored poorer than the 50th percentile for their age and gender. Survivors were categorised as having tinnitus if they reported that for >10% of their time awake, they were consciously aware of their tinnitus. Differences among the chemotherapy groups were evaluated using parametric and non-parametric tests.ResultsFor most of the demographic and clinical characteristics, no differences were found among the three chemotherapy groups. Occurrence rates for audiogram-confirmed hearing loss ranged from 52.3% to 71.4%. Occurrence rates for tinnitus ranged from 37.1% to 40.0%. No differences were found among the three chemotherapy groups in the occurrence rates or effects of hearing loss and tinnitus.ConclusionThese findings suggest that regardless of the chemotherapy regimen common mechanistic pathway(s) may underlie these two neurotoxicities.

BackgroundClinicians' bias related to patients' race and substance use history play a role in pain management. However, patients' or clinicians' understandings about discriminatory practices and the structural factors that contribute to and exacerbate these practices are underexamined. We report on perceptions of discrimination from the perspectives of patients with chronic non-cancer pain (CNCP) and a history of substance use and their clinicians within the structural landscape of reductions in opioid prescribing in the United States.MethodsWe interviewed 46 clinicians and 94 patients, using semi-structured interview guides, from eight safety-net primary care clinics across the San Francisco Bay Area from 2013 to 2020. We used a modified grounded theory approach to code and analyze transcripts.ResultsClinicians discussed using opioid prescribing guidelines with the goals of increased opioid safety and reduced bias in patient monitoring. While patients acknowledged the validity of clinicians' concerns about opioid safety, they indicated that clinicians made assumptions about opioid misuse towards Black patients and patients suspected of substance use. Clinicians discussed evidence of discrimination in opioid prescribing at the clinic-wide level; racialized stereotypes about patients likely to misuse opioids; and their own struggles to overcome discriminatory practices regarding CNCP management.ConclusionWhile clinicians and patients acknowledged opioid safety concerns, the practical application of opioid prescribing guidelines impacted how patients perceived and engaged with CNCP care particularly for patients who are Black and/or report a history of substance use. We recommend healthcare system and clinic-level interventions that may remediate discriminatory practices and associated disparities.

BACKGROUND: Evaluate for differences in occurrence, severity, and distress ratings for 32 symptoms between younger older adults (YOA,

Pain is common and variable in its severity among hospitalized patients with cancer. Although biopsychosocial factors are well established as modulators of chronic pain, less is known about what patient-level factors are associated with worse pain outcomes among hospitalized cancer patients. This prospective cohort study included patients with active cancer presenting to the emergency department (ED) with pain severity of ≥4/10 and followed pain outcomes longitudinally throughout hospital admission. Baseline demographic, clinical, and psychological factors were assessed on ED presentation, and daily average clinical pain ratings and opioid consumption during hospitalization were abstracted. Univariable and multivariable generalized estimating equation analyses examined associations of candidate biopsychosocial, demographic, and clinical predictors with average daily pain and opioid administration. Among 113 hospitalized patients, 73% reported pain as the primary reason for presenting to the ED, 43% took outpatient opioids, and 27% had chronic pain that predated their cancer. Higher pain catastrophizing ( B = 0.1, P ≤ 0.001), more recent surgery ( B = -0.2, P ≤ 0.05), outpatient opioid use ( B = 1.4, P ≤ 0.001), and history of chronic pain before cancer diagnosis ( B = 0.8, P ≤ 0.05) were independently associated with greater average daily pain while admitted to the hospital. Higher pain catastrophizing ( B = 1.6, P ≤ 0.05), higher anxiety ( B = 3.7, P ≤ 0.05), lower depression ( B = -4.9, P ≤ 0.05), metastatic disease ( B = 16.2, P ≤ 0.05), and outpatient opioid use ( B = 32.8, P ≤ 0.001) were independently associated with higher daily opioid administration. Greater psychological distress, especially pain catastrophizing, as well as pain and opioid use history, predicted greater difficulty with pain management among hospitalized cancer patients, suggesting that early assessment of patient-level characteristics may help direct consultation for more intensive pharmacologic and nonpharmacologic interventions.

PURPOSE: Circadian rest-Activity Rhythm Disorders (CARDs) are common in patients with cancer, particularly in advanced disease. CARDs are associated with increased symptom burden, poorer quality of life, and shorter survival. Research and reporting practices lack standardization, and formal diagnostic criteria do not exist. This electronic Delphi (e-Delphi) study aimed to formulate international recommendations for the assessment and diagnosis of CARDs in patients with cancer. METHODS: An international e-Delphi was performed using an online platform (Welphi). Round 1 developed statements regarding circadian rest-activity rhythms, diagnostic criteria, and assessment techniques. Rounds 2 and 3 involved participants rating their level of agreement with the statements and providing comments until consensus (defined internally as 67%) and stability between rounds were achieved. Recommendations were then created and distributed to participants for comments before being finalized. RESULTS: Sixteen participants from nine different clinical specialties and seven different countries, with 5-35 years of relevant research experience, were recruited, and thirteen participants completed all three rounds. Of the 164 generated statements, 66% achieved consensus, and responses were stable between the final two rounds. CONCLUSIONS: The e-Delphi resulted in international recommendations for assessing and diagnosing CARDs in patients with cancer. These recommendations should ensure standardized research and reporting practices in future studies.

BackgroundCancer-related cognitive impairment (CRCI) is a common symptom in patients with breast cancer. In our previous study of 397 women with breast cancer, we identified 3 groups of patients with distinct CRCI profiles (ie, high, moderate, and low-moderate attentional function). Compared with the other 2 classes, the low-moderate class was younger, had more comorbidities, and with lower functional status.ObjectivesIn this study, we expand on this work and evaluate for differences among these latent classes in the severity of psychological (depression and anxiety) and physical (fatigue, decrements in energy, sleep disturbance, and pain) symptoms before surgery.MethodsCancer-related cognitive impairment was assessed using the Attentional Functional Index from before through 6 months after surgery. Lower Attentional Functional Index scores indicate higher levels of CRCI. Psychological and physical symptoms were assessed with valid instruments. Parametric and nonparametric tests were used to evaluate for differences in symptom severity scores among the latent classes.ResultsApproximately 60% of patients experienced CRCI (ie, moderate and low-moderate classes). Significant differences were found among the 3 classes in the severity of trait and state anxiety, depressive symptoms, fatigue, and sleep disturbance (ie, high < moderate < low-moderate). In addition, compared with the other 2 classes, the low-moderate class reported higher pain interference scores.ConclusionsThese findings suggest that women with clinically meaningful levels of persistent CRCI have a relatively high symptom burden before surgery.Implications for practiceClinicians need to routinely perform preoperative assessments of CRCI and associated symptoms and initiate therapeutic interventions.

BACKGROUND: Morning and evening fatigue are distinct and distressing symptoms experienced during chemotherapy that demonstrate a large amount of interindividual variability. OBJECTIVES: The objectives of this study were to identify subgroups of patients with distinct morning and evening fatigue co-occurrence profiles and evaluate for differences among these subgroups in demographic, clinical, and symptom characteristics and quality of life. METHODS: Oncology patients ( n = 1,334) completed the Lee Fatigue Scale to self-report morning and evening fatigue, six times over two cycles of chemotherapy. Latent profile analysis was used to identify subgroups of patients with distinct morning and evening physical fatigue profiles. RESULTS: Four distinct morning and evening fatigue profiles were identified (i.e., Both Low, Low Morning + Moderate Evening, Both Moderate, and Both High). Compared to the Both Low profile, the Both High profile was significantly younger, less likely to be married or partnered, more likely to live alone, had a higher comorbidity burden, and lower functional status. The Both High profile had higher levels of anxiety, depressive symptoms, sleep disturbance, and pain and lower levels of quality of life. DISCUSSION: The variability in the morning and evening severity scores among the four profiles supports the hypothesis that morning and evening fatigue are distinct but related symptoms. Clinically meaningful levels of both morning and evening fatigue were reported by 50.4% of our sample, which suggests that the co-occurrence of these two symptoms is relatively common. Patients in Both Moderate and Both High profiles experienced an extremely high symptom burden that warrants ongoing assessments and aggressive symptom management interventions.

KEY POINTS: Health utility profiles can be identified at 60 days after AKI. Patient subgroups with distinct health utility profiles have different characteristics at index hospitalization and outcomes at 1 year. These profiles may be useful when considering resources to improve the physical and emotional health of patients after AKI. BACKGROUND: A large amount of interindividual variability exists in health-related quality of life outcomes after AKI. This study aimed to determine whether subgroups of early AKI survivors could be identified on the basis of distinct health utility impairment profiles ascertained at 60 days after AKI and whether these subgroups differed in clinical and biomarker characteristics at index hospitalization and outcomes at 1-year follow-up. METHODS: This retrospective analysis used data from the Biologic Markers of Renal Recovery for the Kidney study, an observational subcohort of the Acute Renal Failure Trial Network study. Of 402 patients who survived to 60 days after AKI, 338 completed the Health Utility Index 3 survey, which measures impairments in eight health attributes. Latent class analysis was used to identify subgroups of patients with distinct health utility profiles. RESULTS: Three subgroups with distinct health utility impairment profiles were identified: Low (28% of participants), Moderate (58%), and High (14%) with a median of one, four, and six impairments across the eight health attributes at 60 days after AKI, respectively. Patient subgroups differed in weight, history of cerebrovascular disease, intensity of dialysis, hospital length of stay, and dialysis dependence. Serum creatinine and blood urea nitrogen at index hospitalization did not differ among the three subgroups. The High impairment subgroup had higher levels of IL-6 and soluble TNF receptor 2 at study day 1. The three subgroups had different 1-year mortality rates: 5% in the Low, 21% in the Moderate, and 52% in the High impairment subgroup. CONCLUSION: Patient subgroups with distinct health utility impairment profiles can be identified 60 days after AKI. These subgroups have different characteristics at index hospitalization. A higher level of impairment at 60 days was associated with decreased survival.

AIM: To evaluate older gynecologic oncology patients quality of life (QOL) at the initiation of chemotherapy and compare their QOL scores with a female age-matched general population (GP) sample. DESIGN: Cross-sectional. METHODS: Older (n = 122) gynecologic oncology patients completed the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) that evaluates global health and five functional scales (range from 0 to 100). Differences in QOL scores between our sample and the GP were evaluated using one-sample t-tests and effect sizes were calculated using Cohens d. RESULTS: Patients mean age was 70.7 years (±6.6). Mean scores for the function scales ranged from 58.5 (±31.1) for role function to 86.1 (±17.0) for cognitive function. Compared to the GP, our sample reported significantly lower scores for global health status, social, role and physical functioning, and a significantly higher score for cognitive functioning. No differences were found in emotional functioning scores. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

ObjectiveTo review the state of oncology nursing science as it pertains to big data. The authors aim to define and characterize big data, describe key considerations for accessing and analyzing big data, provide examples of analyses of big data in oncology nursing science, and highlight ethical considerations related to the collection and analysis of big data.Data sourcesPeer-reviewed articles published by investigators specializing in oncology, nursing, and related disciplines.ConclusionBig data is defined as data that are high in volume, velocity, and variety. To date, oncology nurse scientists have used big data to predict patient outcomes from clinician notes, identify distinct symptom phenotypes, and identify predictors of chemotherapy toxicity, among other applications. Although the emergence of big data and advances in computational methods provide new and exciting opportunities to advance oncology nursing science, several challenges are associated with accessing and using big data. Data security, research participant privacy, and the underrepresentation of minoritized individuals in big data are important concerns.Implications for nursing practiceWith their unique focus on the interplay between the whole person, the environment, and health, nurses bring an indispensable perspective to the interpretation and application of big data research findings. Given the increasing ubiquity of passive data collection, all nurses should be taught the definition, characteristics, applications, and limitations of big data. Nurses who are trained in big data and advanced computational methods will be poised to contribute to guidelines and policies that preserve the rights of human research participants.

BackgroundWhile pain is a significant problem for oncology patients, little is known about interindividual variability in pain characteristics.ObjectiveThe aims of this study were to identify subgroups of patients with distinct worst pain severity profiles and evaluate for differences among these subgroups in demographic, clinical, and pain characteristics and stress and symptom scores.MethodsPatients (n = 934) completed questionnaires 6 times over 2 chemotherapy cycles. Worst pain intensity was assessed using a 0- to 10-point numeric rating scale. Brief Pain Inventory was used to assess various pain characteristics. Latent profile analysis was used to identify subgroups of patients with distinct pain profiles.ResultsThree worst pain profiles were identified (low [17.5%], moderate [39.9%], severe [42.6%]). Compared with the other 2 classes, severe class was more likely to be single and unemployed and had a lower annual household income, a higher body mass index, a higher level of comorbidity, and a poorer functional status. Severe class was more likely to have both cancer and noncancer pain, a higher number of pain locations, higher frequency and duration of pain, worse pain quality scores, and higher pain interference scores. Compared with the other 2 classes, severe class reported lower satisfaction with pain management and higher global, disease-specific, and cumulative life stress, as well as higher anxiety, depression, fatigue, sleep disturbance, and cognitive dysfunction scores.ConclusionsUnrelieved pain is a significant problem for more than 80% of outpatients.Implications for practiceClinicians need to perform comprehensive pain assessments; prescribe pharmacologic and nonpharmacologic interventions; and initiate referrals for pain management and psychological services.

OBJECTIVES: Palpitations are common and have a negative impact on womens quality of life. While evidence suggests that inflammatory mechanisms may play a role in the development of palpitations, no studies have evaluated for this association in patients with breast cancer who report palpitations prior to surgery. The purpose of this pilot study was to evaluate for associations between the occurrence of palpitations and single nucleotide polymorphisms (SNPs) in genes for pro- and anti-inflammatory cytokines, their receptors, and transcriptional regulators. METHODS: Patients were recruited prior to surgery and completed a self-report questionnaire on the occurrence of palpitations. Genotyping of SNPs in cytokine genes was performed using a custom array. Multiple logistic regression analyses were done to identify associations between the occurrence of palpitations and SNPs in fifteen candidate genes. RESULTS: Of the 82 SNPs evaluated in the bivariate analyses, eleven SNPs in 6 genes were associated with the occurrence of palpitations. After controlling for functional status, the occurrence of back pain, and self-reported and genomic estimates of race/ethnicity, 3 SNPs in 3 different genes (i.e., interleukin (IL) 1-beta (IL1B) rs1143643, IL10 rs3024505, IL13 rs1295686) were associated with the occurrence of palpitations prior to surgery (all p ≤ .038). CONCLUSIONS: While these preliminary findings warrant replication, they suggest that inflammatory mechanisms may contribute to the subjective sensation of palpitations in women prior to breast cancer surgery.

BackgroundThe SARS-CoV-2 (COVID-19) pandemic increased use of telehealth for the management of opioid use disorder and chronic non-cancer pain in primary care safety net clinical systems. Significant barriers to telehealth exist, little is known about how these barriers impact urban safety net, primary care providers and their patients. The objective of this study was to qualitatively assess the benefits and challenges of telehealth for management of chronic non-cancer pain, opioid use disorder, and multi-morbidity in primary care, safety net clinical systems.MethodsWe interviewed patients with chronic non-cancer pain and history of substance use (n = 22) and their primary care clinicians (n = 7) in the San Francisco Bay Area, March-July 2020. We recorded, transcribed, coded, and content analyzed interviews.ResultsCOVID-19 shelter-in-place orders contributed to increases in substance use and uncontrolled pain, and posed challenges for monitoring opioid safety and misuse through telehealth. None of the clinics used video visits due to low digital literacy/access. Benefits of telehealth included decreased patient burden and missed appointments and increased convenience and control of some chronic conditions (e.g., diabetes, hypertension). Telehealth challenges included loss of contact, greater miscommunication, and less comprehensive care interactions.ConclusionsThis study is one of the first to examine telehealth use in urban safety net primary care patients with co-occurring chronic non-cancer pain and substance use. Decisions to continue or expand telehealth should consider patient burden, communication and technology challenges, pain control, opioid misuse, and medical complexity.

ContextCognitive and physical fatigue are common symptoms experienced by oncology patients. Exposure to stressful life events (SLE), cancer-related stressors, coping styles, and levels of resilience may influence the severity of both dimensions of fatigue.ObjectivesEvaluate for differences in global, cancer-specific, and cumulative life stress, as well as resilience and coping in oncology patients (n=1332) with distinct cognitive fatigue AND evening physical fatigue profiles.MethodsLatent profile analysis, which combined the two symptom scores, identified three subgroups of patients with distinct cognitive fatigue AND evening physical fatigue profiles (i.e., Low, Moderate, High). Patients completed measures of global, cancer-specific, and cumulative life stress as well measures of resilience and coping. Differences among the latent classes in the various measures were evaluated using parametric and nonparametric tests.ResultsCompared to Low class, the other two classes reported higher global and cancer-specific stress. In addition, they reported higher occurrence rates for sexual harassment and being forced to touch prior to 16 years of age. Compared to the other two classes, High class reported lower resilience scores and higher use of denial, substance use, and behavioral disengagement.ConclusionTo decrease both cognitive and evening physical fatigue, clinicians need to assess for relevant stressors and initiate interventions to increase resilience and the use of engagement coping strategies. Additional research is warranted on the relative contribution of various social determinants of health to both cognitive and physical fatigue in oncology patients receiving chemotherapy.

BackgroundUnrelieved chemotherapy-induced nausea (CIN) occurs 48% of patients undergoing chemotherapy and is one of the most debilitating symptoms that patients report.ObjectiveThe aims of this study were to identify subgroups of patients with distinct CIN profiles and determine how these subgroups differed on demographic and clinical characteristics; severity, frequency, and distress of CIN; and the co-occurrence of common gastrointestinal symptoms.MethodsPatients (n = 1343) completed demographic questionnaire and Memorial Symptom Assessment Scale 6 times over 2 cycles of chemotherapy. Latent class analysis was used to identify subgroups of patients with distinct CIN profiles. Differences among these subgroups were evaluated using parametric and nonparametric statistics.ResultsFour distinct CIN profiles were identified: none (40.8%), increasing-decreasing (21.5%), decreasing (8.9%), and high (28.8%). Compared with the none class, patients in the high class were younger, had a lower annual household income, had child care responsibilities, had a lower Karnofsky Performance Status score and a higher Self-administered Comorbidity Questionnaire score, and were more likely to have received chemotherapy on a 14-day cycle and a highly emetogenic chemotherapy regimen. In addition, patients in the high class reported high occurrence rates for dry mouth, feeling bloated, diarrhea, lack of appetite, abdominal cramps, difficulty swallowing, mouth sores, weight loss, and change in the way food tastes.ConclusionsThat 60% of the patients reported moderate to high CIN occurrence rates confirms that this unrelieved symptom is a significant clinical problem.Implications for practiceNurses need to evaluate patients' level of adherence to their antiemetic regimen and make appropriate referrals for physical therapy, psychological services, and dietary counseling.

BackgroundModerate to severe fatigue occurs in up to 94% of patients with cancer. Recent evidence suggests that morning and evening fatigue are distinct dimensions of physical fatigue. The purposes of this study were to evaluate the transcriptome for common and distinct perturbed inflammatory pathways in patients receiving chemotherapy who reported low versus high levels of morning or low versus high levels of evening cancer-related fatigue.MethodsPatients completed questionnaires during the week prior to their chemotherapy treatment. Severity of morning and evening fatigue was evaluated using the Lee Fatigue Scale. Gene expression and pathway impact analyses (PIA) were performed in two independent samples using RNA-sequencing (n = 357) and microarray (n = 360). Patterns of interactions between and among these perturbed pathways were evaluated using a knowledge network (KN).ResultsAcross the PIA, nine perturbed pathways (FDR

PurposeEvaluate for differences in demographic and clinical characteristics, occurrence of common symptoms, symptom severity scores, and quality of life (QOL) outcomes in survivors with (n = 155) and without (n = 118) audiometrically confirmed hearing loss.MethodsSurvivors, who were recruited from throughout the San Francisco Bay area, completed the self-report questionnaires to obtain the information of demographic and clinical characteristics; the occurrence and severity of depression, anxiety, fatigue, decrements in energy, sleep disturbance, pain, and cognitive impairment; and the general and cancer-specific QOL outcomes. Parametric and non-parametric tests were used to evaluate for differences between the two survivor groups.ResultsSurvivors with audiometrically confirmed hearing loss were older, more likely to be male, were more likely to be unemployed, report a lower annual household income, and had a higher comorbidity burden. Except for the severity of worst pain, no between-group differences were found in the occurrence rates for or severity of any of the symptoms. Survivors with hearing loss reported worse physical function and general health scores.ConclusionsWhile no between-group differences in symptom occurrence rates and severity scores were found, across the total sample, a relatively high percentage of survivors who were over 6 years from their cancer diagnosis reported clinically meaningful levels of depression (25%), anxiety (50%), fatigue (40%), decrements in energy (70%), sleep disturbance (58%), cognitive impairment (57%), and pain (60%).Implications for cancer survivorsClinicians need to perform routine assessments of hearing loss, as well as common co-occurring symptoms and initiate individualized symptom management interventions.

PurposeWe aimed to estimate the effect of a 12-week web-based dietary intervention with text messages on quality of life (QoL) among colorectal cancer (CRC) survivors.MethodsBetween 2017 and 2018, 50 CRC survivors were randomized (1:1) to receive a 12-week web-based dietary intervention with daily text messages or wait-list control. Health-related QoL was assessed using the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) and colorectal quality of life module (QLQ-CR29) at baseline, 12, and 24 weeks. Within- and between-group mean changes in health-related QoL with 95% confidence intervals (CI) were calculated for both arms.ResultsCompared to the controls, participants receiving the intervention had an improvement in emotional functioning (mean change: 14.3; 95% CI: 3.0, 25.6) at 12 weeks and social functioning (mean change: 13.8; 95% CI: 2.1, 25.5) at 24 weeks. A decrease of fatigue from baseline was also observed in the intervention arm (mean change: - 9.1; 95% CI: - 17.1, - 1.1) at 24 weeks. No other changes in QoL scores were associated with the intervention.ConclusionCRC survivors randomized to receive a web-based dietary intervention with text messages experienced higher emotional and social functioning. Further study with a larger population may be warranted.Trial registrationclinicaltrials.gov, NCT02965521. Registered 16 November 2016, https://clinicaltrials.gov/ct2/keydates/NCT02965521.

Unrelieved pain occurs in 55% of cancer patients. Identification of molecular mechanisms for pain may provide insights into therapeutic targets. Purpose was to evaluate for perturbations in neuroinflammatory pathways between oncology patients with and without severe pain. Worst pain severity was rated using a 0 to 10 numeric rating scale six times over two cycles of chemotherapy. Latent profile analysis was used to identify subgroups of patients with distinct pain profiles. Pathway impact analyses were performed in two independent samples using gene expression data obtained from RNA sequencing (n = 192) and microarray (n = 197) technologies. Fisher's combined probability test was used to identify significantly perturbed pathways between None versus the Severe pain classes. In the RNA sequencing and microarray samples, 62.5% and 56.3% of patients were in the Severe pain class, respectively. Nine perturbed pathways were related to neuroinflammatory mechanisms (i.e., retrograde endocannabinoid signaling, gamma-aminobutyric acid synapse, glutamatergic synapse, Janus kinase-signal transducer and activator of transcription signaling, phagosome, complement and coagulation cascades, cytokine-cytokine receptor interaction, chemokine signaling, calcium signaling). First study to identify perturbations in neuroinflammatory pathways associated with severe pain in oncology outpatients. Findings suggest that complex neuroimmune interactions are involved in the maintenance of chronic pain conditions. Perspective: In this study that compared oncology patients with none versus severe pain, nine perturbed neuroinflammatory pathways were identified. Findings suggest that complex neuroimmune interactions are involved in the maintenance of persistent pain conditions.

Objective/backgroundSleep disturbance is a common problem in patients receiving chemotherapy. Purpose was to evaluate for perturbations in immune-inflammatory pathways between oncology patients with low versus very high levels of sleep disturbance.Patients/methodsSleep disturbance was evaluated using the General Sleep Disturbance Scale six times over two cycles of chemotherapy. Latent profile analysis was used to identify subgroups of patients with distinct sleep disturbance profiles. Pathway impact analyses were performed in two independent samples using gene expression data obtained from RNA sequencing (n = 198) and microarray (n = 162) technologies. Fisher's combined probability test was used to identify significantly perturbed pathways between Low versus Very High sleep disturbance classes.ResultsIn the RNA sequencing and microarray samples, 59.1% and 51.9% of patients were in the Very High sleep disturbance class, respectively. Thirteen perturbed pathways were related to immune-inflammatory mechanisms (i.e., endocytosis, phagosome, antigen processing and presentation, natural killer cell mediated cytotoxicity, cytokine-cytokine receptor interaction, apoptosis, neutrophil extracellular trap formation, nucleotide-binding and oligomerization domain-like receptor signaling, Th17 cell differentiation, intestinal immune network for immunoglobulin A production, T-cell receptor signaling, complement and coagulation cascades, and tumor necrosis factor signaling).ConclusionsFirst study to identify perturbations in immune-inflammatory pathways associated with very high levels of sleep disturbance in oncology outpatients. Findings suggest that complex immune-inflammatory interactions underlie sleep disturbance.

BackgroundUp to 45% of patients report cancer-related cognitive impairment (CRCI). A variety of characteristics are associated with the occurrence and/or severity of CRCI. However, an important gap in knowledge of risk factors for CRCI is the relative contribution of each factor. The multifactorial model of cancer-related cognitive impairment (MMCRCI) is a conceptual model of CRCI that can be used to evaluate the strength of relationships between various factors and CRCI.ObjectivesThe purpose of this study was to use structural regression methods to evaluate the MMCRCI using data from a large sample of outpatients receiving chemotherapy ( n = 1,343). Specifically, the relationships between self-reported CRCI and four MMCRCI concepts (i.e., social determinants of health, patient-specific factors, treatment factors, and co-occurring symptoms) were examined. The goals were to determine how well the four concepts predicted CRCI and determine the relative contribution of each concept to deficits in perceived cognitive function.MethodsThis study is part of a larger, longitudinal study that evaluated the symptom experience of oncology outpatients receiving chemotherapy. Adult patients were diagnosed with breast, gastrointestinal, gynecological, or lung cancer; had received chemotherapy within the preceding 4 weeks; were scheduled to receive at least two additional cycles of chemotherapy; were able to read, write, and understand English; and gave written informed consent. Self-reported CRCI was assessed using the attentional function index. Available study data were used to define the latent variables.ResultsOn average, patients were 57 years of age, college educated, and with a mean Karnofsky Performance Status score of 80. Of the four concepts evaluated, whereas co-occurring symptoms explained the largest amount of variance in CRCI, treatment factors explained the smallest amount of variance. A simultaneous structural regression model that estimated the joint effect of the four exogenous latent variables on the CRCI latent variable was not significant.DiscussionThese findings suggest that testing individual components of the MMCRCI may provide useful information on the relationships among various risk factors, as well as refinements of the model. In terms of risk factors for CRCI, co-occurring symptoms may be more significant than treatment factors, patient-specific factors, and/or social determinants of health in patients receiving chemotherapy.

BACKGROUND: Patients undergoing cancer treatment experience global stress and cancer-specific stress. Both types of stress are associated with a higher symptom burden. OBJECTIVE: In this cross-sectional study, we used a comprehensive set of demographic, clinical, and symptom characteristics to evaluate their relative contribution to the severity of global and cancer-specific stress. METHODS: Patients (N = 941) completed study questionnaires before their second or third cycle of chemotherapy. RESULTS: Consistent with our a priori hypothesis, we found both common and distinct characteristics associated with higher levels of global stress and cancer-specific stress. A significant proportion of our patients had scores on the Impact of Event Scale-Revised suggestive of subsyndromal (29.4%) or probable (13.9%) posttraumatic stress disorder. Four of the 5 stepwise linear regression analyses for the various stress scales explained between 41.6% and 54.5% of the total variance. Compared with various demographic and clinical characteristics, many of the common symptoms associated with cancer and its treatments uniquely explained a higher percentage of the variance in the various stress scales. Symptoms of depression made the largest unique contribution to the percentage of total explained variance across all 5 scales. CONCLUSION: Clinicians need to assess for global stress, cancer-specific stress, and depression in patients receiving chemotherapy. IMPLICATIONS FOR PRACTICE: Patients may benefit from integrative interventions (eg, mindfulness-based stress reduction, cognitive behavioral therapy, acupuncture) that simultaneously address stress and symptoms commonly associated with cancer and its treatments.

BackgroundA psychological symptom cluster is the most common cluster identified in oncology patients. Although inflammatory mechanisms are hypothesized to underlie this cluster, epigenetic contributions are unknown.ObjectivesThis study's purpose was to evaluate associations between the occurrence of a psychological symptom cluster and levels of DNA methylation for inflammatory genes in a heterogeneous sample of patients with cancer receiving chemotherapy.MethodsPrior to their second or third cycle of chemotherapy, 1,071 patients reported the occurrence of 38 symptoms using the Memorial Symptom Assessment Scale. A psychological cluster was identified using exploratory factor analysis. Differential methylation analyses were performed in two independent samples using Illumina Infinium 450K and EPIC microarrays. Expression-associated CpG (eCpG) loci in the promoter region of 114 inflammatory genes on the 450K and 112 genes on the EPIC microarray were evaluated for associations with the psychological cluster. Robust rank aggregation was used to identify differentially methylated genes across both samples. Significance was assessed using a false discovery rate of 0.05 under the Benjamini-Hochberg procedure.ResultsCluster of differentiation 40 ( CD40 ) was differentially methylated across both samples. All six promoter eCpGs for CD40 that were identified across both samples were hypomethylated in the psychological cluster group.ConclusionsThis study is the first to suggest associations between a psychological symptom cluster and differential DNA methylation of a gene involved in tissue inflammation and cell-mediated immunity. Our findings suggest that increased CD40 expression through hypomethylation of promoter eCpG loci is involved in the occurrence of a psychological symptom cluster in patients receiving chemotherapy. These findings suggest a direction for mechanistic studies.

BACKGROUND: We sought to determine the population-level associations between persistent pain and subsequent changes in physical function, cognitive function, and well-being, outcomes important to older adults. METHODS: We used data from National Health Aging Trends Study (NHATS) of community-dwelling Medicare beneficiaries age 65+ from 2011 to 2019. We defined persistent pain as being bothered by pain in the last month in both the 2011and 2012 interviews and intermittent pain including those reporting bothersome pain in one interview only. We used competing risks regression to estimate the association between persistent pain and the development of clinically meaningful declines in physical function, cognitive function, and well-being, adjusting for age, sex, race, education, and marital status at baseline. RESULTS: Of the 5589 eligible NHATS participants, 38.7% reported persistent pain and 27.8% reported intermittent pain. Over one-third described pain in five or more sites. Over the subsequent 7 years, participants with persistent pain were more likely to experience declines in physical function (64% persistent pain, 59% intermittent pain, 57% no bothersome pain; aHR 1.14, 95% CI 1.05-1.23) and well-being (48% persistent pain, 45% intermittent pain, 44% no bothersome pain; aHR 1.11, 95% CI 1.01-1.21), but were not more likely to experience cognitive decline (25% persistent pain, 24% intermittent pain, 23% no bothersome pain; aHR 1.02, 95% CI 0.90-1.16). CONCLUSIONS: Persistent pain is common in older adults and occurs in multiple body sites. Persistent pain contributes to meaningful declines in physical function and well-being over 7 years and warrants proactive interventions to mitigate pain.

ObjectivesWhile the gastrointestinal symptom cluster (GISC) is common in patients receiving chemotherapy, limited information is available on its underlying mechanism(s). Emerging evidence suggests a role for inflammatory processes through the actions of the nuclear factor kappa B (NF-κB) signaling pathway. This study evaluated for associations between a GISC and levels of DNA methylation for genes within this pathway.MethodsPrior to their second or third cycle of chemotherapy, 1071 outpatients reported symptom occurrence using the Memorial Symptom Assessment Scale. A GISC was identified using exploratory factor analysis. Differential methylation analyses were performed in two independent samples using EPIC (n = 925) and 450K (n = 146) microarrays. Trans expression-associated CpG (eCpG) loci for 56 NF-κB signaling pathway genes were evaluated. Loci significance were assessed using an exploratory false discovery rate (FDR) of 25% for the EPIC sample. For the validation assessment using the 450K sample, significance was assessed at an unadjusted p-value of 0.05.ResultsFor the EPIC sample, the GISC was associated with increased expression of lymphotoxin beta (LTB) at one differentially methylated trans eCpG locus (cg03171795; FDR = 0.168). This association was not validated in the 450K sample.ConclusionsThis study is the first to identify an association between a GISC and epigenetic regulation of a gene that is involved in the initiation of gastrointestinal immune responses. Findings suggest that increased LTB expression by hypermethylation of a trans eCpG locus is involved in the occurrence of this cluster in patients receiving chemotherapy. LTB may be a potential therapeutic target for this common cluster.

PurposeStudy purposes were to evaluate for inter-individual variability in the trajectories of three objective measures of physical function (PF) in older patients receiving chemotherapy (n = 112) and determine which characteristics were associated with worse PF.MethodsBalance, gait speed, and chair-stand test were evaluated at initiation and 1, 3, 6, 9, and 12 months following chemotherapy. Hierarchical linear modeling was used to assess inter-individual variability in the trajectories of the three tests. Demographic, clinical, and symptom characteristics, and levels of cognitive function associated with initial levels and changes over time in each of the tests were determined.ResultsGait speed and chair-stand tests improved over time. Balance declined until month 6, then increased. Characteristics associated with decreases in balance scores at initiation of chemotherapy were lower level of education and lower Karnofsky Performance Status (KPS) score. For initial levels of poorer gait speed, older age, poorer Trail Making Test B (TMTB), and worse Attentional Function Index scores were the associated characteristics. Lower KPS scores, higher body mass index, and poorer TMTB scores were associated with poorer chair-stand times at initiation of chemotherapy. Worse trajectories of chair-stand times were associated with poorer chair-stand time at enrollment. Characteristic associated with lower initial levels and improved trajectories of balance was older age at enrollment.ConclusionsDetermination of characteristics associated with decrements in balance, gait speed, and chair-stand can assist clinicians to identify older oncology patients at risk for decrements in PF. Interventions to maintain and improve PF need to be implemented with higher risk patients.

Background: Breast cancer survivors who report chronic pain in the affected ipsilateral upper limb or body are nearly twice as likely to develop lymphedema. Little is known about lymphatic pain, defined as co-occurring pain and swelling in the affected ipsilateral upper limb or body. The study aimed to examine the predictors and effects of lymphatic pain on breast cancer survivors activities of daily living (ADLs). Materials and Methods: A sample of 568 patients was recruited in a metropolitan cancer center in the United States. Demographic and clinical data were collected. Body mass index (BMI) and limb volume were measured using infra-red perometer. Lymphatic pain and ADLs were measured by the Lymphedema and Breast Cancer Symptom Experience Index. Parametric and nonparametric tests and generalized linear models were used to analyze data. Results: Lymphatic pain affected 33% of survivors. Significant predictors of lymphatic pain included younger age, higher BMI, financial hardship, and a diagnosis of lymphedema. Patients with a diagnosis of lymphedema had 9.68 odds (confidence interval [CI]: 5.78-16.63; p 5% and >10% compared to patients with only pain and no symptom. Conclusion: This study is the first to report that in a large sample of patients, 33.1% experienced lymphatic pain and that lymphatic pain was associated with significant impairments in ADLs. Findings suggest that lymphatic pain may be due to abnormal accumulation of lymph fluid. Research is needed to ascertain the physiological mechanisms that underlie lymphatic pain and determine whether strategies to prevent and treat lymphedema can decrease lymphatic pain.

BACKGROUND: Patients with head and neck cancer experience psychoneurological symptoms (PNS) (i.e., depression, fatigue, sleep disturbance, pain, and cognitive dysfunction) during intensity-modulated radiotherapy (IMRT) that decrease their functional status, quality of life, and survival rates. The purpose of this study was to examine and visualize the relationships among PNS within networks over time and evaluate for demographic and clinical characteristics associated with symptom networks. METHODS: A total of 172 patients (mean age, 59.8 ± 9.9 years; 73.8%, male; 79.4%, White) completed symptom questionnaires four times, namely, before IMRT (T1), 1 month (T2), 3 months (T3), and 12 months (T4) post IMRT. Network analysis was used to examine the symptom-symptom relationships among PNS. Centrality indices, including strength, closeness, and betweenness, were used to describe the degrees of symptom network interconnections. Network comparison test was used to assess the differences between two symptom networks. RESULTS: Depression was associated with the other four symptoms, and fatigue was associated with the other three symptoms across the four assessments. Based on the centrality indices, depression (rstrength  = 1.3-1.4, rcloseness  = 0.06-0.08, rbetweeness  = 4-10) was the core symptom in all symptom networks, followed by fatigue. Female gender, higher levels of stress, and no alcohol use were associated with stronger symptom networks in network global strength before IMRT. CONCLUSION: Network analysis provides a novel approach to gain insights into the relationships among self-reported PNS and identify the core symptoms and associated characteristics. Clinicians may use this information to develop symptom management interventions that target core symptoms and interconnections within a network. LAY SUMMARY: This study describes the symptom-symptom relationships for five common symptoms in patients with head and neck cancer receiving radiotherapy. Depression and fatigue appeared to be two core symptoms that were connected with sleep disturbance, pain, and cognitive dysfunction within a network. Several characteristics (i.e., female, higher stress, no alcohol use) were associated with stronger symptom networks.

Oncology patients experience numerous co-occurring symptoms during their treatment. The identification of sentinel/core symptoms is a vital prerequisite for therapeutic interventions. In this study, using Network Analysis, we investigated the inter-relationships among 38 common symptoms over time (i.e., a total of six time points over two cycles of chemotherapy) in 987 oncology patients with four different types of cancer (i.e., breast, gastrointestinal, gynaecological, and lung). In addition, we evaluated the associations between and among symptoms and symptoms clusters and examined the strength of these interactions over time. Eight unique symptom clusters were identified within the networks. Findings from this research suggest that changes occur in the relationships and interconnections between and among co-occurring symptoms and symptoms clusters that depend on the time point in the chemotherapy cycle and the type of cancer. The evaluation of the centrality measures provides new insights into the relative importance of individual symptoms within various networks that can be considered as potential targets for symptom management interventions.

Two conceptual approaches are used to evaluate symptom clusters: "clustering" symptoms (ie, variable-centered analytic approach) and "clustering" patients (ie, person-centered analytic approach). However, these methods are not used consistently and conceptual clarity is needed. Given the emergence of novel methods to evaluate symptom clusters, a review of the conceptual basis for older and newer analytic methods is warranted. Therefore, this article will review the conceptual basis for symptom cluster research; compare and contrast the conceptual basis for using variable-centered versus patient-centered analytic approaches in symptom cluster research; review their strengths and weaknesses; and compare their applications in symptom cluster research.

BackgroundThe delivery of optimal care depends on accurate communication between patients and clinicians regarding untoward symptoms. Documentation of patients’ symptoms necessitates reliance on memory, which is often imprecise. We developed an electronic diary (eDiary) for adolescents and young adults (AYAs) with cancer to record symptoms. ObjectiveThe purpose of this paper is to describe the utility of an eDiary designed for AYAs with cancer, including dependability of the mobile application, the reasons for any missing recorded data, patients’ adherence rates to daily symptom queries, and patients’ perceptions of the usefulness and acceptability of symptom data collection via mobile phones. MethodsOur team developed an electronic symptom diary based on interviews conducted with AYAs with cancer and their clinicians. This diary included daily severity ratings of pain, nausea, vomiting, fatigue, and sleep. The occurrence of other selected physical sequelae was assessed daily. Additionally, patients selected descriptors of their mood. A 3-week trial of the eDiary was conducted with 10 AYA cancer patients. Mobile phones with service plans were loaned to patients who were instructed to report their symptoms daily. Patients completed a brief questionnaire and were interviewed to elicit their perceptions of the eDiary and any technical difficulties encountered. ResultsOverall adherence to daily symptom reports exceeded 90%. Young people experienced few technical difficulties and reported benefit from daily symptom reports. Symptom occurrence rates were high and considerable inter- and intra-patient variability was noted in symptom and mood reports. ConclusionsWe demonstrated the utility of an eDiary that may contribute insight into patients’ symptom patterns to promote effective symptom management.

PurposeRelatively few studies have evaluated for symptom clusters across multiple dimensions. It is unknown whether the symptom dimension used to create symptom clusters influences the number and types of clusters that are identified. Study purposes were to describe ratings of occurrence, severity, and distress for 38 symptoms in a heterogeneous sample of oncology patients (n = 1329) undergoing chemotherapy; identify and compare the number and types of symptom clusters based on three dimensions (i.e., occurrence, severity, and distress); and identify common and distinct clusters.MethodsA modified version of the Memorial Symptom Assessment Scale was used to assess the occurrence, severity, and distress ratings of 38 symptoms in the week prior to patients' next cycle of chemotherapy. Symptom clusters for each dimension were identified using exploratory factor analysis.ResultsPatients reported an average of 13.9 (±7.2) concurrent symptoms. Lack of energy was both the most common and severe symptom while "I don't look like myself" was the most distressing. Psychological, gastrointestinal, weight gain, respiratory, and hormonal clusters were identified across all three dimensions. Findings suggest that psychological, gastrointestinal, and weight gain clusters are common while respiratory and hormonal clusters are distinct.ConclusionsPsychological, gastrointestinal, weight gain, hormonal, and respiratory clusters are stable across occurrence, severity, and distress in oncology patients receiving chemotherapy. Given the stability of these clusters and the consistency of the symptoms across dimensions, the use of a single dimension to identify these clusters may be sufficient. However, comprehensive and disease-specific inventories need to be used to identify distinct clusters.

Background: In patients with lymphedema (LE), in addition to hand dominance, between-group comparisons of interlimb soft tissue differences need to account for differences in whole-body adiposity, measured directly by dual energy X-ray absorptiometry (DXA) or indirectly by body mass index. No study has evaluated the effects of hand dominance and whole-body adiposity on limb composition in patients with LE. This studys purpose was to compare soft tissue composition of affected and unaffected limbs of women with breast cancer, who did and did not have LE, controlling for dominance and percent body fat. Methods and Results: Whole-body DXA scans were acquired and included measures of percent body fat, upper limb total mass, upper limb fat mass, and upper limb fat-free mass. Participants were classified into one of three groups: women without LE; women with only subjective LE; and women with objective signs of LE at the time of assessment. Differences among the LE groups were evaluated using analysis of variance (ANOVA) and Chi-square analyses. Analysis of covariance (ANCOVA) was used to control for percent body fat and for the affected limb dominance. Compared to women without LE, women with objective signs of LE have greater total limb mass, fat mass, and fat-free mass in their affected limbs, independent of affected side dominance and percent body fat. In addition, the interlimb differences in total mass, fat mass, and fat-free mass were greater for the women with objective signs of LE, compared to the other two groups. Conclusions: DXA is useful in identifying soft tissue changes in patients with LE. Given that limb circumferences measure only changes in limb volume and that bioimpedance provides estimates of extracellular fluid, DXA has the advantage of being able to estimate the volumes of specific tissues in the limb.