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

Supplemental Material for Gastrointestinal Symptom Cluster is Associated With Epigenetic Regulation of Lymphotoxin Beta in Oncology Patients Receiving Chemotherapy by Carolyn S. Harris, PhD, RN, Christine A. Miaskowski, PhD, RN, Yvette P. Conley, PhD, Marilyn J. Hammer, PhD, DC, RN, Anand A. Dhruva, MD, Jon D. Levine, MD, PhD, Adam B. Olshen, PhD, MA, and Kord M. Kober, PhD in Biological Research For Nursing

BackgroundPurposes were to identify subgroups of patients with gastrointestinal cancers with distinct morning and evening fatigue severity profiles and evaluate for differences among these subgroups in demographic and clinical characteristics, co-occurring symptoms and quality of life (QOL) outcomes.MethodsPatients with gastrointestinal cancers (n=405) completed questionnaires six times over two cycles of chemotherapy. Latent profile analysis was used to identify distinct morning and evening fatigue profiles. Differences in demographic and clinical characteristics, co-occurring symptoms and QOL outcomes among the subgroups were evaluated using parametric and nonparametric tests.ResultsTwo distinct mornings (ie, low and very high) and three distinct evenings (ie, low, moderate and very high) fatigue classes were identified. Common risk factors for both morning and evening fatigue included younger age, lower performance status, higher comorbidity burden and self-reported depression. Higher levels of morning fatigue were associated with being unmarried, living alone, being unemployed, having a lower income, lack of regular exercise and a self-reported diagnosis of anaemia. Higher levels of evening fatigue were associated with being women, white and having childcare responsibilities. Patients in the very high morning and evening fatigue classes reported higher levels of anxiety, depressive symptoms, sleep disturbance and pain and lower levels of attentional function and poorer QOL.ConclusionFindings provide new insights into risk factors for and deleterious effects of morning and evening fatigue in patients with gastrointestinal cancers. Clinicians can use this information to identify high-risk patients and develop individualised interventions for morning and evening fatigue and other co-occurring symptoms.

PurposeFatigue is the most common symptom associated with cancer and its treatment. Investigation of molecular mechanisms associated with fatigue in oncology patients may identify new therapeutic targets. The objectives of this study were to evaluate the relationships between gene expression and perturbations in biological pathways and evening fatigue severity in oncology patients who received chemotherapy (CTX).MethodsThe Lee Fatigue Scale (LFS) and latent class analysis were used to identify evening fatigue phenotypes. We measured 47,214 ribonucleic acid transcripts from whole blood collected prior to a cycle of CTX. Perturbations in biological pathways associated with differential gene expression were identified from public data sets (i.e., Kyoto Encyclopedia Gene and Genomes, BioCarta).ResultsPatients were classified into Moderate (n=65, mean LFS score 3.1) or Very High (n=195, mean LFS score 6.4) evening fatigue groups. Compared to patients with Moderate fatigue, patients with Very High fatigue exhibited differential expression of 29 genes. A number of the perturbed pathways identified validated prior mechanistic hypotheses for fatigue, including alterations in immune function, inflammation, neurotransmission, energy metabolism, and circadian rhythms. Based on our findings, energy metabolism was further divided into alterations in carbohydrate metabolism and skeletal muscle energy. Alterations in renal function-related pathways were identified as a potential new mechanism.ConclusionsThis study identified differential gene expression and perturbed biological pathways that provide new insights into the multiple and likely inter-related mechanisms associated with evening fatigue in oncology patients.