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Association between pro- and anti-inflammatory cytokine genes and a symptom cluster of pain, fatigue, sleep disturbance, and depression.

ABSTRACT: Because multiple symptoms associated with "sickness behavior" have a negative impact on functional status and quality of life, increased information on the mechanisms that underlie inter-individual variability in this symptom experience is needed. The purposes of this study were to determine: if distinct classes of individuals could be identified based on their experience with pain, fatigue, sleep disturbance, and depression; if these classes differed on demographic and clinical characteristics; and if variations in pro- and anti- inflammatory cytokine genes were associated with latent class membership. Self-report measures of pain, fatigue, sleep disturbance, and depression were completed by 168 oncology outpatients and 85 family caregivers (FCs). Using latent class profile analysis (LCPA), three relatively distinct classes were identified: those who reported low depression and low pain (83%), those who reported high depression and low pain (4.7%), and those who reported high levels of all four symptoms (12.3%). The minor allele of IL4 rs2243248 was associated with membership in the "All high" class along with younger age, being White, being a patient (versus a FC), having a lower functional status score, and having a higher number of comorbid conditions. Findings suggest that LPCA can be used to differentiate distinct phenotypes based on a symptom cluster associated with sickness behavior. Identification of distinct phenotypes provides new evidence for the role of IL4 in the modulation of a sickness behavior symptom cluster in oncology patients and their FCs.

SUBMITTER: Illi J

PROVIDER: S-EPMC3340525 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Association between pro- and anti-inflammatory cytokine genes and a symptom cluster of pain, fatigue, sleep disturbance, and depression.

Illi Julie J Miaskowski Christine C Cooper Bruce B Levine Jon D JD Dunn Laura L West Claudia C Dodd Marylin M Dhruva Anand A Paul Steven M SM Baggott Christina C Cataldo Janine J Langford Dale D Schmidt Brian B Aouizerat Bradley E BE

Cytokine 20120324 3

Because multiple symptoms associated with "sickness behavior" have a negative impact on functional status and quality of life, increased information on the mechanisms that underlie inter-individual variability in this symptom experience is needed. The purposes of this study were to determine: if distinct classes of individuals could be identified based on their experience with pain, fatigue, sleep disturbance, and depression; if these classes differed on demographic and clinical characteristics; ...[more]

PMID: 22450224

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Project description:CONTEXT:Symptom researchers have proposed a model of inflammatory cytokine activity and dysregulation in cancer to explain co-occurring symptoms including pain, fatigue, and sleep disturbance. OBJECTIVES:We tested the hypothesis that psychological stress accentuates inflammation and that stress and inflammation contribute to one's experience of the pain, fatigue, and sleep disturbance symptom cluster (symptom cluster severity, symptom cluster distress) and its impact (symptom cluster interference with daily life, quality of life). METHODS:We used baseline data from a symptom cluster management trial. Adult participants (N = 158) receiving chemotherapy for advanced cancer reported pain, fatigue, and sleep disturbance on enrollment. Before intervention, participants completed measures of demographics, perceived stress, symptom cluster severity, symptom cluster distress, symptom cluster interference with daily life, and quality of life and provided a blood sample for four inflammatory biomarkers (interleukin-1?, interleukin-6, tumor necrosis factor-?, and C-reactive protein). RESULTS:Stress was not directly related to any inflammatory biomarker. Stress and tumor necrosis factor-? were positively related to symptom cluster distress, although not symptom cluster severity. Tumor necrosis factor-? was indirectly related to symptom cluster interference with daily life, through its effect on symptom cluster distress. Stress was positively associated with symptom cluster interference with daily life and inversely with quality of life. Stress also had indirect effects on symptom cluster interference with daily life, through its effect on symptom cluster distress. CONCLUSION:The proposed inflammatory model of symptoms was partially supported. Investigators should test interventions that target stress as a contributing factor in co-occurring pain, fatigue, and sleep disturbance and explore other factors that may influence inflammatory biomarker levels within the context of an advanced cancer diagnosis and treatment.

Project description:PurposeBreast cancer survivors following disease-modifying treatment frequently experience multiple-concurrent symptoms (Jansana et al. in Int J Cancer 149(10):1755 1767, 2021), negatively impacting their quality of life and increasing the risk of polypharmacy (Alwhaibi et al. in J Oncol Pharm Pract 26(5):1052 1059, 2020). This study evaluates the feasibility and acceptability of acupuncture for the management of the pain-fatigue-sleep disturbance-numbness/tingling symptom cluster in breast cancer survivors, and investigates relationships between the symptom cluster and Traditional Chinese Medicine (TCM) syndrome diagnosis.MethodsThis was a single-arm, pre-test/post-test feasibility trial conducted at Chris O'Brien Lifehouse Hospital, Australia. Breast cancer survivors who completed treatment and experienced clinically significant levels of two or more symptoms (pain, fatigue, sleep disturbance, numbness/tingling) were eligible to participate in the individualized, pragmatic 6-week acupuncture intervention. The primary outcome was feasibility and acceptability. Effectiveness was explored using a symptom cluster mean score.ResultsTwenty women enrolled in the study over an 11-week period and 90% completed the study. Most women agreed or completely agreed that acupuncture was feasible (85%), acceptable (90%), and appropriate (90%). Both mean and composite symptom cluster scores were significantly reduced (p < 0.001), as were individual symptom scores in fatigue (p < 0.001), sleep disturbance (p = 0.04), and numbness/tingling (p = 0.01). TCM syndromes most closely associated with this symptom cluster were Spleen qi deficiency and Heart fire. No adverse events were reported.ConclusionThis study demonstrated that acupuncture was safe and feasible, justifying a powered randomized control trial. Preliminary findings suggest beneficial effects of acupuncture for the management of the pain-fatigue-sleep disturbance-numbness/tingling symptom cluster for women with breast cancer. TCM syndromes identified in this trial may be used to guide acupuncture treatment protocols.Clinical trial registrationThis trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622000590763) on 21 April 2022.

Project description:BackgroundSomatic acupoint stimulation (SAS) has been frequently utilised as a promising intervention for individual cancer-related symptom management, such as fatigue, sleep disturbance and depression. However, research evidence regarding the role of SAS in mitigating the fatigue-sleep disturbance-depression symptom cluster (FSDSC) has been scant. This study was conducted to develop an evidence-based SAS intervention protocol that can be further implemented in a Phase II randomized controlled trial (RCT) to manage the FSDSC in breast cancer survivors.MethodsThe Medical Research Council Framework for Developing and Evaluating Complex Intervention (MRC framework) was employed to guide the development procedures of the SAS intervention protocol, including the identification of an existing evidence base, the identification of theories and practice standards, and the validation of the SAS intervention protocol. A content validity study was performed through an expert panel to assess the scientific and practical appropriateness of the SAS intervention protocol. The content validity index (CVI), including item-level CVI and protocol-level CVI, were calculated to evaluate the consensus level of the expert panel.ResultsKey components of the SAS protocol, including the acupoint formula, the SAS modality, technique, intensity and frequency were identified for both a true and placebo SAS intervention based on the best available research evidence retrieved from systematic reviews, clinical trials, and relevant theories, particularly regarding the inflammatory process, yin-yang theory, zang-fu organs and meridians theory, and acupressure practical standards. The true SAS intervention was determined as daily self-administered acupressure on specific acupoints for seven weeks. The placebo SAS was designed as light acupressure on non-acupoints with the same frequency and duration as the true SAS. Excellent content validity was achieved after one round of expert panel assessment, with all the key components of the true and placebo SAS protocols rated as content valid (CVI ranged from 0.86 to 1.00).ConclusionsA research-informed, theory-driven and practically feasible SAS intervention protocol for the FSDSC management in breast cancer survivors was developed following the MRC framework. The feasibility and acceptability of the SAS intervention will be further tested in breast cancer survivors through a Phase II RCT.

Project description:IntroductionThe fatigue-sleep disturbance-depression (FSD) symptom cluster, as one of the most common symptom clusters in breast cancer (BC) survivors, can significantly decrease patients' quality of life. Since the management of the FSD symptom cluster has been unsatisfactory with the use of pharmacological treatments alone, non-pharmacological approaches have, therefore, been recommended. Somatic acupressure (SA) is a promising approach given its potential benefits of cancer-related symptom alleviation and the convenience of self-practice. However, research evidence on using acupressure to manage the FSD symptom cluster has been limited. The proposed trial aims to examine the feasibility and preliminary effects of an evidence-based SA intervention for FSD symptom cluster management in BC survivors.Methods and analysisThis study will be a phase II randomised controlled trial with three study arms and 1:1:1 allocation. Fifty-one early-stage BC survivors who are experiencing the FSD symptom cluster will be randomly assigned to a true SA group, a sham SA group or a usual care group. All participants will receive an education booklet regarding FSD symptom cluster management advice as the usual care package. The participants in the true SA group will additionally receive a 7-week self-administered SA intervention. The participants in the sham SA group will additionally receive self-administered light acupressure at non-acupoints with the same frequency, session and duration as the true SA group. The primary outcomes will be feasibility outcomes related to subject recruitment and completion of study questionnaires and interventions. The secondary outcomes will be the effects of SA on fatigue, sleep disturbance, depression and quality of life. Descriptive statistics will be used to present all the outcomes. The secondary outcomes will be analysed using an intent-to-treat approach.Ethics and disseminationEthical approvals of this trial have been granted by the Human Research Ethics Committee at Charles Darwin University (H19017) and the Clinical Trial Ethics Committee at The Affiliated Hospital of Southwest Medical University (KY2019039). Findings from this trial will be published in peer-reviewed journals and presented at professional conferences.Trial registration numberThis trial was registered at ClinicalTrials.gov and the registration number is NCT04118140, with the stage at Recruiting.

Dataset Information

Association between pro- and anti-inflammatory cytokine genes and a symptom cluster of pain, fatigue, sleep disturbance, and depression.

Publications

Association between pro- and anti-inflammatory cytokine genes and a symptom cluster of pain, fatigue, sleep disturbance, and depression.

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