Gastrointestinal and Neuropsychological Symptoms Are Associated With Distinct Vomiting Profiles in Patients Receiving Chemotherapy.

OBJECTIVES: To identify subgroups of patients with distinct chemotherapy-induced vomiting (CIV) profiles; determine how these subgroups differ on several demographic, clinical, and symptom characteristics; and evaluate factors associated with chemotherapy-induced nausea and CIV profiles. SAMPLE & SETTING: Adult patients (N = 1,338) receiving cancer chemotherapy. METHODS & VARIABLES: Data were collected on demographic, clinical, and symptom characteristics. Differences among subgroups of patients with distinct CIV profiles were evaluated using parametric and nonparametric tests. RESULTS: Three CIV profiles (None, Decreasing, and Increasing) were identified. Compared with the None class, Decreasing and Increasing classes were more likely to have lower household income and a higher comorbidity burden, as well as to report higher rates of dry mouth, nausea, diarrhea, depression, anxiety, sleep disturbance, morning fatigue, and pain interference. IMPLICATIONS FOR NURSING: Clinicians need to assess common and distinct risk factors for CIV and chemotherapy-induced nausea.

Higher Levels of Stress and Neuropsychological Symptoms Are Associated With a High Nausea Profile in Patients With Cancer Receiving Chemotherapy.

OBJECTIVES: To evaluate differences in the severity of global, cancer-specific, and cumulative life stress, resilience, and common neuropsychological symptoms among four subgroups of patients with distinct chemotherapy-induced nausea (CIN) profiles. SAMPLE & SETTING: Adult patients with cancer (N = 1,343) receiving chemotherapy. METHODS & VARIABLES: Patients completed stress, resilience, and neuropsychological symptom severity measures. The Memorial Symptom Assessment Scale was used to assess CIN occurrence six times over two cycles of chemotherapy. Parametric and nonparametric statistics were used to evaluate differences among subgroups of patients with distinct CIN profiles. RESULTS: The high class had significantly higher levels of global, cancer-specific, and cumulative life stress; significantly higher levels of depression, anxiety, sleep disturbance, morning and evening fatigue, and pain; and lower levels of morning and evening energy and cognitive dysfunction. IMPLICATIONS FOR NURSING: Clinicians need to evaluate CIN occurrence across each cycle of chemotherapy and assess patients for various types of stress and common neuropsychological symptoms.

Multiple Gastrointestinal Symptoms Are Associated With Chemotherapy-Induced Nausea in Patients With Breast Cancer.

BACKGROUND: Unrelieved chemotherapy-induced nausea (CIN) is a significant problem for patients with breast cancer (BC). OBJECTIVE: In a sample of patients with BC who were assessed before their second or third cycle of chemotherapy, study purposes were to evaluate for the occurrence, severity, frequency, and distress associated with CIN; evaluate for differences in demographic and clinical characteristics and gastrointestinal (GI) symptom occurrence rates between patients who did and did not report CIN; and determine which demographic, clinical, and symptom characteristics were associated with the occurrence of CIN. METHODS: Patients completed demographic and clinical questionnaires and the Memorial Symptom Assessment Scale for nausea and common GI symptom assessments. Univariate analyses evaluated for differences in demographic and clinical characteristics and GI symptom occurrence between patients who did and did not report CIN. Multiple logistic regression analysis evaluated for characteristics associated with CIN. RESULTS: Of the 532 patients with BC, 47.2% reported CIN occurrence. Characteristics associated with CIN group membership were poorer functional status, receipt of chemotherapy on a 14-day cycle, and higher occurrence rates of 5 GI symptoms (ie, dry mouth, vomiting, constipation, change in the way food tastes, and lack of appetite; all P < .001). CONCLUSIONS: Unrelieved CIN is a common symptom in patients with BC. This study is the first to demonstrate that 5 co-occurring GI symptoms were associated with CIN occurrence. IMPLICATIONS FOR PRACTICE: This study identified new risk factors for CIN occurrence in patients with BC. Clinicians may be able to initiate additional interventions to alleviate CIN.

Alterations in Patterns of Gene Expression and Perturbed Pathways in the Gut-Brain Axis Are Associated With Chemotherapy-Induced Nausea.

CONTEXT: Despite current advances in antiemetic treatments, approximately 50% of oncology patients experience chemotherapy-induced nausea (CIN). OBJECTIVES: The purpose of this study was to evaluate for differentially expressed genes and perturbed pathways associated with the gut-brain axis (GBA) across two independent samples of oncology patients who did and did not experience CIN. METHODS: Oncology patients (n = 735) completed study questionnaires in the week before their second or third cycle of chemotherapy. CIN occurrence was assessed using the Memorial Symptom Assessment Scale. Gene expression analyses were performed in two independent samples using ribonucleic acid sequencing (Sample 1, n = 357) and microarray (Sample 2, n = 352) methodologies. Fisher's combined probability method was used to determine genes that were differentially expressed and pathways that were perturbed between the two nausea groups across both samples. RESULTS: CIN was reported by 63.6% of the patients in Sample 1 and 48.9% of the patients in Sample 2. Across the two samples, 703 genes were differentially expressed, and 37 pathways were found to be perturbed between the two CIN groups. We identified nine perturbed pathways that are involved in mechanisms associated with alterations in the GBA (i.e., mucosal inflammation, disruption of gut microbiome). CONCLUSION: Persistent CIN remains a significant clinical problem. Our study is the first to identify novel GBA-related pathways associated with the occurrence of CIN. Our findings warrant confirmation and suggest directions for future clinical studies to decrease CIN occurrence.

Mechanisms and Measurement of Changes in Gene Expression.

Research on gene expression (GE) provides insights into the physiology of a cell or group of cells at a given point in time. Studies of changes in GE can be used to identify patients at higher risk for various medical conditions, a higher symptom burden, and/or the adverse consequences associated with various treatments. The aims of this article are as follows: (1) to describe the different types of RNA transcripts, (2) to describe the processes involved in GE (i.e., RNA transcription, epigenetics, and posttranscriptional modifications), (3) to describe common sources of variation in GE, (4) to describe the most common methods used to measure GE, and (5) to discuss factors to consider when choosing tissue for a GE study. This article begins with an overview of the mechanisms involved in GE. Then, the factors that can influence the findings from GE experiments (e.g., tissue specificity, host age, host gender, and time of sample collection) are described and potential solutions are presented. This article concludes with a discussion of how the types of tissue used in GE studies can affect study findings. Given that the costs associated with the measurement of changes in GE are decreasing and the methods to analyze GE data are becoming easier to use, nurse scientists need to understand the basic principles that underlie any GE study.

A review of the literature on the relationships between genetic polymorphisms and chemotherapy-induced nausea and vomiting.

Despite current advances in antiemetic treatments, between 30% to and 60% of oncology patients experience chemotherapy-induced nausea (CIN) and 13% to 33% report chemotherapy-induced vomiting (CIV). Inter-individual differences are observed in the occurrence and severity of chemotherapy-induced nausea and vomiting (CINV). This review summarizes and critiques studies on associations between occurrence and severity of CINV and polymorphisms in serotonin receptor, drug metabolism, and drug transport pathway genes. Sixteen studies evaluated the associations between the occurrence and/or severity of CINV and single nucleotide polymorphisms (SNPs). Across these studies, three SNPs in 5-hydroxytryptamine receptor (5-HT3R) genes, two alleles of the cytochrome P450 family 2 subfamily D member 6 (CYP2D6) gene, and three SNPs in ATP binding cassette subfamily B member 1 (ABCB1) gene were associated with the occurrence and severity of CINV. Given the limited number of polymorphisms evaluated, additional research is warranted to identify new mechanisms to develop more targeted therapies.

Risk Factors Associated With Chemotherapy-Induced Nausea in the Week Before the Next Cycle and Impact of Nausea on Quality of Life Outcomes.

CONTEXT: Despite current advances in antiemetic treatments, between 19% and 58% of oncology patients experience chemotherapy-induced nausea (CIN). OBJECTIVES: Aims of this post hoc exploratory analysis were to determine occurrence, severity, and distress of CIN and evaluate for differences in demographic and clinical characteristics, symptom severity, stress; and quality of life (QOL) outcomes between oncology patients who did and did not report CIN in the week before chemotherapy (CTX). Demographic, clinical, symptom, and stress characteristics associated with CIN occurrence were determined. METHODS: Patients (n = 1296) completed questionnaires that provided information on demographic and clinical characteristics, symptom severity, stress, and QOL. Univariate analyses evaluated for differences in demographic and clinical characteristics, symptom severity, stress, and QOL scores between the two patient groups. Multiple logistic regression analysis was used to evaluate for factors associated with nausea group membership. RESULTS: Of the 1296 patients, 47.5% reported CIN. In the CIN group, 15% rated CIN as severe and 23% reported high distress. Factors associated with CIN included less education; having childcare responsibilities; poorer functional status; higher levels of depression, sleep disturbance, evening fatigue, and intrusive thoughts; as well as receipt of CTX on a 14-day CTX cycle and receipt of an antiemetic regimen that contained serotonin receptor antagonist and steroid. Patients in the CIN group experienced clinically meaningful decrements in QOL. CONCLUSION: This study identified new factors (e.g., poorer functional status, stress) associated with CIN occurrence. CIN negatively impacted patients' QOL. Pre-emptive and ongoing interventions may alleviate CIN occurrence in high-risk patients.

A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R.

IL-23 is a heterodimeric cytokine composed of the IL-12p40 "soluble receptor" subunit and a novel cytokine-like subunit related to IL-12p35, termed p19. Human and mouse IL-23 exhibit some activities similar to IL-12, but differ in their capacities to stimulate particular populations of memory T cells. Like IL-12, IL-23 binds to the IL-12R subunit IL-12Rbeta1. However, it does not use IL-12Rbeta2. In this study, we identify a novel member of the hemopoietin receptor family as a subunit of the receptor for IL-23, "IL-23R." IL-23R pairs with IL-12Rbeta1 to confer IL-23 responsiveness on cells expressing both subunits. Human IL-23, but not IL-12, exhibits detectable affinity for human IL-23R. Anti-IL-12Rbeta1 and anti-IL-23R Abs block IL-23 responses of an NK cell line and Ba/F3 cells expressing the two receptor chains. IL-23 activates the same Jak-stat signaling molecules as IL-12: Jak2, Tyk2, and stat1, -3, -4, and -5, but stat4 activation is substantially weaker and different DNA-binding stat complexes form in response to IL-23 compared with IL-12. IL-23R associates constitutively with Jak2 and in a ligand-dependent manner with stat3. The ability of cells to respond to IL-23 or IL-12 correlates with expression of IL-23R or IL-12Rbeta2, respectively. The human IL-23R gene is on human chromosome 1 within 150 kb of IL-12Rbeta2.