Perturbations in inflammatory pathways are associated with shortness of breath profiles in oncology patients receiving chemotherapy.

PURPOSE: One 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. METHODS: Patients 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. RESULTS: Twenty-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. CONCLUSIONS: Findings 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.

Stability and consistency of symptom clusters in younger versus older patients receiving chemotherapy.

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 (< 60 years) versus older (≥ 60 years) oncology patients undergoing chemotherapy and to evaluate for differences in the stability and consistency of symptom clusters across the two age groups. METHODS: A total of 1329 patients were dichotomized into the younger and older groups. Patients completed demographic and clinical questionnaires prior to the initiation of their second or third cycle of chemotherapy. A modified version of Memorial Symptom Assessment Scale was used to evaluate the occurrence, severity, and distress of 38 common symptoms associated with cancer and its treatment. Differences between the two age groups in demographic and clinical characteristics and ratings of occurrence, severity, and distress for the 38 symptoms were evaluated using parametric and nonparametric tests. Exploratory factor analyses were done within each age group to identify symptom clusters using symptom occurrence rates. RESULTS: Compared to the younger group (14.8 (± 7.0)), older adults reported a lower mean number of symptoms (12.9 (± 7.2)). Older patients experienced lower occurrence rates for almost 50% of the symptoms. Regarding symptom clusters, an eight-factor solution was selected for both age groups. Across the two age groups, the eight symptom clusters (i.e., physical and cognitive fatigue, respiratory, psychological, hormonal, chemotherapy-related toxicity, weight gain, gastrointestinal, epithelial) were stable. However, symptoms within the physical and cognitive, chemotherapy-related toxicity, and gastrointestinal clusters were not consistent across the age groups. CONCLUSIONS: To be able to provide tailored and effective symptom management interventions to older oncology patients, routine assessments of the core symptoms unique to the symptom clusters identified for this group warrants consideration. The underlying mechanism(s) for these inconsistencies in symptom burden is an important focus for future studies.

Anxiety in oncology outpatients is associated with perturbations in pathways identified in anxiety focused network pharmacology research.

PURPOSE: Evaluate 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. METHODS: Adult 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. RESULTS: In 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. CONCLUSIONS: Findings 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.

Antiracist symptom science: A call to action and path forward.

Nurse scientists recognize the experience of racism as a driving force behind health. However, symptom science, a pillar of nursing, has rarely considered contributions of racism. Our objective is to describe findings within symptom science research related to racial disparities and/or experiences of racism and to promote antiracist symptom science within nursing research. In this manuscript, we use an antiracist lens to review a predominant symptom science theory and literature in three areas of symptom science research-oncology, mental health, and perinatal health. Finally, we make recommendations for increasing antiracist research in symptom science by altering (a) research questions, (b) recruitment methods, (c) study design, (d) data analysis, and (e) dissemination of findings. Traditionally, symptom science focuses on individual level factors rather than broader contexts driving symptom experience and management. We urge symptom science researchers to embrace antiracism by designing research with the specific intent of dismantling racism at multiple levels.

Cancer-related cognitive impairment is associated with perturbations in inflammatory pathways.

Cancer-related cognitive impairment (CRCI) is a significant problem for patients receiving chemotherapy. While a growing amount of pre-clinical and clinical evidence suggests that inflammatory mechanisms underlie CRCI, no clinical studies have evaluated for associations between CRCI and changes in gene expression. Therefore, the purpose of this study was to evaluate for differentially expressed genes and perturbed inflammatory pathways across two independent samples of patients with cancer who did and did not report CRCI. The Attentional Function Index (AFI) was the self-report measure used to assess CRCI. AFI scores of <5 and of >7.5 indicate low versus high levels of cognitive function, respectively. Of the 185 patients in Sample 1, 49.2% had an AFI score of <5 and 50.8% had an AFI score of >7.5. Of the 158 patients in Sample 2, 50.6% had an AFI score of <5 and 49.4% had an AFI score of >7.5. Data from 182 patients in Sample 1 were analyzed using RNA-seq. Data from 158 patients in Sample 2 were analyzed using microarray. Twelve KEGG signaling pathways were significantly perturbed between the AFI groups, five of which were signaling pathways related to inflammatory mechanisms (e.g., cytokine-cytokine receptor interaction, tumor necrosis factor signaling). This study is the first to describe perturbations in inflammatory pathways associated with CRCI. Findings highlight the role of cytokines both in terms of cytokine-specific pathways, as well as pathways involved in cytokine production and cytokine activation. These findings have the potential to identify new targets for therapeutics and lead to the development of interventions to improve cognition in patients with cancer.

Anxiety profiles are associated with stress, resilience and symptom severity in outpatients receiving chemotherapy.

PURPOSE: The purposes of this study, in a sample of oncology patients (n = 1326) receiving chemotherapy, were to identify subgroups of patients with distinct anxiety profiles and evaluate for differences in demographic and clinical characteristics, stress and resilience measures, and severity of co-occurring symptoms (i.e., depression, sleep disturbance, attentional function, fatigue, pain). METHODS: Patients completed self-report questionnaires a total of six times over two cycles of chemotherapy. Severity of state anxiety was evaluated using the Spielberger State Anxiety Inventory and resilience was assessed using the Connor-Davidson Resilience Scale. Symptoms were assessed using the Center for Epidemiologic Studies Depression Scale, General Sleep Disturbance Scale, Lee Fatigue Scale, Attentional Function Index and Brief Pain Inventory. RESULTS: Based on the findings from the latent profile analysis that utilized the six assessments of state anxiety, 47.7% of the patients were classified as "Low," 28.3% as "Moderate," 19.5% as "High," and 4.5.% as "Very High." Anxiety levels remained relatively stable across the six timepoints. Compared to the Low class, membership in the Moderate, High, and Very High classes was associated with a number of characteristics (e.g., younger age, female gender, lower functional status, more comorbidities). Those patients with higher levels of anxiety reported higher levels of stress, lower levels of resilience, and increased severity of co-occurring symptoms. CONCLUSION: Our findings suggest that a substantial number of oncology patients may warrant referral to psychological services. Clinicians need to perform systematic assessments of anxiety, stress, and common symptoms and initiate appropriate interventions to enhance resilience and coping.

Associations Between Preoperative Shortness of Breath and Potassium Channels Gene Variations in Women With Breast Cancer.

OBJECTIVES: Shortness of breath is a common symptom in patients with cancer. However, the mechanisms that underlie this troublesome symptom are poorly understood. Therefore, this study aimed to determine the prevalence of and associated risk factors for shortness of breath in women prior to breast cancer surgery and identify associations between shortness of breath and polymorphisms for potassium channel genes. METHODS: Patients were recruited prior to breast cancer surgery and completed a self-report questionnaire on the occurrence of shortness of breath. Genotyping of single nucleotides polymorphism (SNPs) in potassium channel genes was performed using a custom array. Multiple logistic regression analyses were done to identify associations between the occurrence of shortness of breath and SNPs in ten candidate genes. RESULTS: Of the 398 patients, 11.1% reported shortness of breath. These patients had a lower annual household income, a higher comorbidity burden, and a lower functional status. After controlling for functional status, comorbidity burden, genomic estimates of ancestry and self-reported race and ethnicity, the genetic associations that remained significant in the multiple regression analyses were for potassium voltage-gated channel subfamily D (KCND2) rs12673992, potassium voltage-gated channel modifier subfamily S (KCNS1) rs4499491, and potassium two pore channel subfamily K (KCNK2) rs4411107. CONCLUSIONS: While these findings warrant replication, they suggest that alterations in potassium channel function may contribute to the occurrence of shortness of breath in women prior to breast cancer surgery.

Lower Income, Smoking, Cardiopulmonary Comorbidities, and Higher Symptom Burden Influence the Occurrence of Cough in Patients Receiving Chemotherapy.

OBJECTIVES: To identify subgroups of patients with distinct cough occurrence profiles and evaluate for differences among these subgroups. SAMPLE & SETTING: Outpatients receiving chemotherapy (N = 1,338) completed questionnaires six times over two chemotherapy cycles. METHODS & VARIABLES: Occurrence of cough was assessed using the Memorial Symptom Assessment Scale. Latent class analysis was used to identify subgroups with distinct cough occurrence profiles. Parametric and nonparametric tests were used to evaluate for differences. RESULTS: Four distinct cough profiles were identified (None, Decreasing, Increasing, and High). Risk factors associated with membership in the High class included lower annual household income; history of smoking; self-reported diagnoses of lung disease, heart disease, and back pain; and having lung cancer. IMPLICATIONS FOR NURSING: Clinicians need to assess all patients with cancer for cough and provide targeted interventions.

Various types of stress and greater use of disengagement coping are associated with worse sleep disturbance in oncology patients undergoing chemotherapy.

Various types of stress and the choice of coping strategies may be risk factors for higher levels of sleep disturbance in oncology patients. Purposes were to evaluate for differences in global, cancer-specific, and cumulative life stress, as well as resilience and the use of coping strategies among three subgroups of patients with distinct sleep disturbance profiles (i.e., Low, High, Very High). Oncology outpatients (n = 1331) completed measures of global (Perceived Stress Scale), cancer-specific (Impact of Event Scale-Revised), and cumulative life (Life Stressor Checklist-Revised) stress, resilience (Connor-Davidson Resilience Scale) and coping (Brief Cope) prior to their second or third cycle of chemotherapy. Sleep disturbance was assessed six times over two chemotherapy cycles. Differences were evaluated using parametric and non-parametric tests. All stress measures showed a dose response effect (i.e., as the sleep disturbance profile worsened, levels of all types of stress increased). Compared to Low class, the other two classes reported higher levels of global perceived stress and higher occurrence rates and effect from previous stressful life events. Impact of Event Scale-Revised scores for the Very High class indicated post-traumatic symptomatology. Patients in High and Very High classes had resilience scores below the normative score for the United States population and used a higher number of disengagement coping strategies. Our findings suggest that very high levels of sleep disturbance are associated with higher levels of various types of stress, lower levels of resilience, and higher use of disengagement coping strategies. Clinicians need to perform routine assessments and implement symptom management interventions to reduce stress and encourage the use of engagement coping strategies.

Stress and Coping in Patients With Cancer With Depression and Sleep Disturbance.

OBJECTIVES: To evaluate for differences in global, cancer-specific, and cumulative life stress, as well as resilience and use of various coping strategies among five groups (no depression or sleep disturbance, no depression and moderate sleep disturbance, subsyndromal depression and very high sleep disturbance, moderate depression and moderate sleep disturbance [Both Moderate]; and high depression and very high sleep disturbance [Both High]). SAMPLE & SETTING: Patients (N = 1,331) receiving chemotherapy were recruited from outpatient oncology clinics. METHODS & VARIABLES: Measures of global, cancer-specific, and cumulative life stress, resilience, and coping were obtained. Differences were evaluated using parametric and nonparametric tests. RESULTS: Global and cancer-specific stress scores increased as joint profiles worsened. Both Moderate and Both High classes had cancer-specific stress scores suggestive of post-traumatic stress. Both Moderate and Both High classes reported higher occurrence rates for several stressful life events and higher use of disengagement coping. Both Moderate and Both High classes had resilience scores below the normative score for the United States. IMPLICATIONS FOR NURSING: Clinicians need to screen vulnerable patients for post-traumatic stress disorder and implement interventions to reduce stress.

Chronic Decrements in Energy in Women with Breast Cancer are Associated with Cytokine Gene Polymorphisms.

OBJECTIVES: Decrements in energy were found in 67% of women who underwent breast cancer surgery. However, no information is available on chronic decrements in energy and associations with inflammation. Purposes were to identify latent classes of patients with distinct average energy profiles from prior to through 12 months after breast cancer surgery; evaluate for differences in demographic and clinical characteristics between the two extreme average energy classes; and evaluate for polymorphisms for cytokine genes associated with membership in the Low energy class. METHODS: Women (n = 397) completed assessments of energy prior to and for 12 months following breast cancer surgery. Growth mixture modeling was used to identify classes of patients with distinct average energy profiles. Eighty-two single nucleotide polymorphisms (SNPs) among 15 cytokine genes were evaluated. RESULTS: Three distinct energy profiles were identified (ie, Low [27.0%], Moderate [54.4%], Changing [18.6%]). Data from patients in the Low and Moderate energy classes were used in the candidate gene analyses. Five SNPs and one haplotype in six different genes remained significant in logistic regression analyses (ie, interleukin [IL]-1ß rs1143623, IL1 receptor 1 rs3917332 IL4 rs2243263, IL6 HapA1 [that consisted of rs1800795, rs2069830, rs2069840, rs1554606, rs2069845, rs2069849, and rs2069861], nuclear factor kappa beta subunit 1 rs170731, tumor necrosis factor rs1799964). For several SNPs for IL6, expression quantitative trait locis were identified in subcutaneous and visceral adipose tissue and thyroid tissue. In addition, skeletal muscle was identified as an expression quantitative trait loci for nuclear factor kappa beta subunit 1. CONCLUSIONS: Findings suggest that cytokine genes are involved in the mechanisms that underlie chronic decrements in energy in women following breast cancer surgery. Given the roles of subcutaneous and visceral adipose and thyroid tissues in metabolism and energy balance, the findings related to IL6 suggest that these polymorphisms may have a functional role in the development and maintenance of chronic decrements in energy.

Worse Depression Profiles Are Associated With Higher Symptom Burden and Poorer Quality of Life in Patients With Gynecologic Cancer.

BACKGROUND: Depression is a pervasive symptom in patients with gynecological cancer undergoing chemotherapy. OBJECTIVES: Purposes were to identify subgroups of patients with distinct depression profiles and evaluate for differences in demographic and clinical characteristics, severity of common symptoms, and quality of life (QOL) outcomes among these subgroups. METHODS: Patients with gynecological cancer (n = 231) completed the Center for Epidemiologic Studies-Depression Scale 6 times over 2 cycles of chemotherapy. All of the other measures were completed prior to the second or third cycle of chemotherapy. Latent profile analysis was done to identify the distinct depression profiles. Differences were evaluated using parametric and nonparametric tests. RESULTS: Three distinct profiles were identified: low (60.1%), high (35.1%), and very high (4.8%). Compared with low class, the other 2 classes had lower functional status and were more likely to self-report a diagnosis of depression. Patients in the 2 worse profiles reported a higher comorbidity burden, higher levels of trait and state anxiety, sleep disturbance, and fatigue, as well as lower levels of cognitive function and poorer QOL. State and trait anxiety, evening fatigue, and sleep disturbance scores exhibit a "dose-response effect" (ie, as the depression profile worsened, the severity of these symptoms increased). CONCLUSIONS: Almost 40% of our sample experienced high or very high levels of depression across 2 cycles of chemotherapy. IMPLICATIONS FOR PRACTICE: Clinicians can use the identified risk factors to identify high patients risk and provide tailored psychological interventions aimed to decrease symptom burden and prevent decrements in QOL.

Self-Reported Cancer-Related Cognitive Impairment in Patients With Breast Cancer Is Associated With Potassium Channel Gene Polymorphisms.

OBJECTIVES: To evaluate for associations of polymorphisms for potassium channel genes in patients with breast cancer who were classified as having high or low-moderate levels of cancer-related cognitive impairment (CRCI). SAMPLE & SETTING: 397 women who were scheduled to undergo surgery for breast cancer on one breast were recruited from breast care centers located in a comprehensive cancer center, two public hospitals, and four community practices. METHODS & VARIABLES: CRCI was assessed using the Attentional Function Index prior to and for six months after surgery. The attentional function classes were identified using growth mixture modeling. RESULTS: Differences between patients in the high versus low-moderate attentional function classes were evaluated. Six single nucleotide polymorphisms for potassium channel genes were associated with low-moderate class membership. IMPLICATIONS FOR NURSING: The results contribute to knowledge of the mechanisms for CRCI. These findings may lead to the identification of high-risk patients and the development of novel therapeutics.

Common and distinct risk factors that influence more severe and distressing shortness of breath profiles in oncology outpatients.

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.

Non-pharmacological interventions on anxiety and depression in lung cancer patients' informal caregivers: A systematic review and meta-analysis.

BACKGROUND: Lung cancer is one of the common cancers and the leading cause of death. Tremendous caregiving burden of informal caregivers of lung cancer causes psychological disorders, such as anxiety and depression. Interventions for informal caregivers of patients with lung cancer to improve their psychological health, which ultimately leads to patients' positive health outcomes, are crucial. A systematic review and meta-analysis was conducted to: 1) evaluate the effect of non-pharmacological interventions on the outcomes of depression and anxiety for lung cancer patients' informal caregivers; and 2) compare the effects of interventions with differing characteristics (i.e. intervention types, mode of contact, and group versus individual delivery). METHODS: Four databases were searched to identify relevant studies. Inclusion criteria for the articles were peer-reviewed non-pharmacological intervention studies on depression and anxiety in lung cancer patients' informal caregivers published between January 2010 and April 2022. Systematic review procedures were followed. Data analysis of related studies was conducted using the Review Manager Version 5.4 software. Intervention effect sizes and studies' heterogeneity were calculated. RESULTS: Eight studies from our search were eligible for inclusion. Regarding total effect for the caregivers' levels of anxiety and depression, results revealed evidence for significant moderate effects of intervention on anxiety (SMD -0.44; 95% CI, -0.67, -0.21; p = 0.0002) and depression (SMD -0.46; 95% CI, -0.74, -0.18; p = 0.001). Subgroup analyses for both anxiety and depression of informal caregivers revealed moderate to high significant effects for specific intervention types (cognitive behavioral and mindfulness combined with psycho-education interventions), mode of contact (telephone-based interventions), and group versus individual delivery. CONCLUSION: This review provides evidence that cognitive behavioral and mindfulness-based, telephone-based, individual or group-based interventions were effective for informal caregivers of lung cancer patients. Further research is needed to develop the most effective intervention contents and delivery methods across informal caregivers with larger sample size in randomized controlled trials.

Systematic review of the literature on the occurrence and characteristics of dyspnea in oncology patients.

BACKGROUND: Dyspnea is a common and distressing symptom for oncology patients.However, dyspnea is not well-characterized and often underestimated by clinicians. This systematic review summarizes the prevalence, intensity, distress, and impact of dyspnea in oncology patients and identifies research gaps. METHODS: A search of all of the relevant databases was done from 2009 to May 2022. A qualitative synthesis of the extant literature was performed using established guidelines. RESULTS: One hundred-seventeen studies met inclusion criteria. Weighted grand mean prevalence of dyspnea in patients with advanced cancer was 58.0%. Intensity of dyspnea was most common dimension evaluated, followed by the impact and distress. Depression and anxiety were the most common symptoms that co-occurred with dyspnea. CONCLUSION: Numerous methodologic challenges were evident across studies. Future studies need to use valid and reliable measures; evaluate the impact of dyspnea; and determine biomarkers for dyspnea.

Multifactorial Model of Dyspnea in Patients With Cancer.

PROBLEM IDENTIFICATION: Dyspnea is a common and distressing symptom for patients with cancer. Although the risk factors for dyspnea in patients with cancer are likely to be multifactorial, a comprehensive description of these risk factors and associated mechanisms is not available in the extant literature. LITERATURE SEARCH: A search of all relevant databases, including Cochrane Library, PubMed®, Embase®, Web of Science, and CINAHL®, was done from January 2009 to May 2022. Case-control and cohort studies that had either a cross-sectional or longitudinal design, as well as randomized controlled trials, were included in the review. Peer-reviewed, full-text articles in English were included. Nineteen studies reported on risk factors for dyspnea. DATA EVALUATION: The methodologic quality of each study was examined using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. SYNTHESIS: A number of factors can influence the occurrence and severity of dyspnea. Using the Mismatch Theory of Dyspnea as the central core of this Multifactorial Model of Dyspnea in Patients With Cancer, the factors included in this conceptual model are person, clinical, and cancer-related factors, as well as respiratory muscle weakness, co-occurring symptoms, and stress. IMPLICATIONS FOR PRACTICE: The Multifactorial Model of Dyspnea in Patients With Cancer can be used by clinicians to evaluate for multiple factors that contribute to dyspnea and to develop individualized and multilevel interventions for patients experiencing this symptom.

Higher Lifetime Stress and Symptom Burden Contribute to the Occurrence of Shortness of Breath.

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.

Oncology Outpatients With Worse Anxiety and Sleep Disturbance Profiles Are at Increased Risk for a Higher Symptom Burden and Poorer Quality of Life.

BACKGROUND: Anxiety and sleep disturbance are frequent symptoms during chemotherapy. OBJECTIVES: Purposes 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. METHODS: Oncology 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. RESULTS: Three 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. CONCLUSIONS: More 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 PRACTICE: Clinicians need to assess for the co-occurrence of anxiety and sleep disturbance.

Perturbations in common and distinct inflammatory pathways associated with morning and evening fatigue in outpatients receiving chemotherapy.

BACKGROUND: Moderate 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. METHODS: Patients 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). RESULTS: Across the PIA, nine perturbed pathways (FDR < 0.025) were common to both morning and evening fatigue, six were distinct for morning fatigue, and four were distinct for evening fatigue. KN (19 nodes, 39 edges) identified the phosphatidylinositol 3-kinase (PI3K)-Akt pathway node (perturbed in evening fatigue) with the highest betweenness (0.255) and closeness (0.255) centrality indices. The next highest betweenness centrality indices were seen in pathways perturbed in evening fatigue (i.e., nuclear factor kappa B: 0.200, natural killer cell-mediated cytotoxicity: 0.178, mitogen-activated protein kinase: 0.175). CONCLUSIONS: This study describes perturbations in common and distinct inflammatory pathways associated with morning and/or evening fatigue. PI3K-Akt was identified as a bottleneck pathway. The analysis identified potential targets for therapeutic interventions for this common and devastating clinical problem.