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.

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.

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.

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.

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.

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.

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.

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.

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.

Neurotransmitter Gene Polymorphisms Are Associated with Symptom Clusters in Patients Undergoing Radiation Therapy.

OBJECTIVES: Purpose was to evaluate for associations between the severity of three distinct symptom clusters (ie, sickness-behavior, mood-cognitive, treatment-related) and polymorphisms for 16 genes involved in catecholaminergic, GABAergic, and serotonergic neurotransmission. DATA SOURCES: Patients with breast and prostate cancer (n = 157) completed study questionnaires at the completion of radiation therapy. Memorial Symptom Assessment Scale was used to assess the severity of 32 common symptoms. Three distinct symptom clusters were identified using exploratory factor analysis. Associations between the symptom cluster severity scores and neurotransmitter gene polymorphisms were evaluated using regression analyses. CONCLUSION: Severity scores for the sickness-behavior symptom cluster were associated with polymorphisms for solute carrier family 6 (SLC6A) member 2 (SLC6A2), SLC6A3, SLC6A1, and 5-hydroxytryptamine receptor (HTR) 2A (HTR2A) genes. For the mood-cognitive symptom cluster, severity scores were associated with polymorphisms for adrenoreceptor alpha 1D, SLC6A2, SLC6A3, SLC6A1, HTR2A, and HTR3A. Severity scores for the treatment-related symptom cluster were associated with polymorphisms for SLC6A2, SLC6A3, catechol-o-methyltransferase, SLC6A1, HTR2A, SLC6A4, and tryptophan hydroxylase 2. IMPLICATIONS FOR NURSING PRACTICE: Findings suggest that polymorphisms for several neurotransmitter genes are involved in the severity of sickness-behavior, mood-cognitive, and treatment-related symptom clusters in oncology patients at the completion of radiation therapy. Four genes with various associated polymorphisms were common across the three distinct symptom clusters (ie, SLC6A2, SLC6A3, SLC6A1, HTR2A) which suggest that these clusters have common underlying mechanisms.

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.

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.

Distinct Shortness of Breath Profiles in Oncology Outpatients Undergoing Chemotherapy.

CONTEXT: Shortness of breath is a distressing symptom that occurs in 10% to 70% of oncology patients. Despite this broad range in its occurrence, little is known about inter-individual variability in shortness of breath and associated risk factors among patients receiving chemotherapy. OBJECTIVES: Identify subgroups of patients with distinct shortness of breath profiles; evaluate for differences among these subgroups in demographic and clinical characteristics; evaluate for differences among symptom dimensions of shortness of breath, and evaluate for differences in quality of life outcomes. METHODS: Outpatients (n=1338) completed questionnaires six times over two chemotherapy cycles. 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. RESULTS: Four distinct shortness of breath profiles were identified (None [70.5%], Decreasing [8.2%], Increasing [7.8%], High [13.5%]). Risk factors for membership in High class included: history of smoking, self-reported diagnosis of lung disease, having lung cancer, and receipt of a higher number of cancer treatments. Compared to the None class, High class reported poorer physical, psychological, and social functioning. CONCLUSIONS: Almost 14% of patients with heterogeneous types of cancer receiving chemotherapy had persistently high occurrence rates of shortness of breath for almost two months. In addition, compared to the Decreasing and Increasing classes, the High class' episodes of shortness of breath were more frequent and more severe. Clinicians need to assess all oncology patients for shortness of breath and provide targeted interventions.

Higher Stress in Oncology Patients is Associated With Cognitive and Evening Physical Fatigue Severity.

CONTEXT: Cognitive 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. OBJECTIVES: Evaluate 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. METHODS: Latent 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. RESULTS: Compared 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. CONCLUSION: To 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.

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.

Sleep disturbance is associated with perturbations in immune-inflammatory pathways in oncology outpatients undergoing chemotherapy.

OBJECTIVE/BACKGROUND: Sleep 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/METHODS: Sleep 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. RESULTS: In 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). CONCLUSIONS: First 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.

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.

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.

Distinct Worst Pain Profiles in Oncology Outpatients Undergoing Chemotherapy.

BACKGROUND: While pain is a significant problem for oncology patients, little is known about interindividual variability in pain characteristics. OBJECTIVE: The 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. METHODS: Patients (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. RESULTS: Three 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. CONCLUSIONS: Unrelieved pain is a significant problem for more than 80% of outpatients. IMPLICATIONS FOR PRACTICE: Clinicians need to perform comprehensive pain assessments; prescribe pharmacologic and nonpharmacologic interventions; and initiate referrals for pain management and psychological services.

Perturbations in Neuroinflammatory Pathways Are Associated With a Worst Pain Profile in Oncology Patients Receiving Chemotherapy.

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.