Debra E. Lyon

Symptom clusters and quality of life in survivors of lung cancer

PURPOSE/OBJECTIVES To explore the prevalence and intensity of depression, fatigue, and pain in survivors of lung cancer; to examine the relationship of symptoms in a cluster; and to examine the relationship of the symptom cluster to quality of life (QOL). DESIGN Secondary data analysis. SETTING Online lung cancer support group. SAMPLE 51 patients diagnosed with lung cancer. METHODS Mailed survey with self-report of depression, fatigue, and pain measured by subscales of the Short-Form 36 Health Status Survey and QOL measured by the Fox Simple QOL Scale. Pearsons correlation and multiple regression analyses were used to examine the possible symptom cluster. MAIN RESEARCH VARIABLES Depression, fatigue, pain, and QOL. FINDINGS Depression, fatigue, and pain were found in a majority of survivors, with pain being the least common symptom. Fatigue was the most intense of the three symptoms. Two significantly correlated symptoms were depression and fatigue. The cluster explained 29% (p less than 0.01) of the variance in QOL in the lung cancer survivors. CONCLUSIONS The data provided preliminary support for the presence of a symptom cluster in patients with lung cancer consisting of depression and fatigue. The cluster had a negative relationship with QOL. Survivors of lung cancer have depression and fatigue that affect QOL. IMPLICATIONS FOR NURSING Healthcare providers must assess the potential for symptoms to cluster, adversely affecting key patient outcomes such as QOL. Through increased knowledge of symptom clusters, clinicians will be able to more effectively target the most distressing set of symptoms for intervention.

Cytokine Comparisons Between Women With Breast Cancer and Women With a Negative Breast Biopsy

Background: Understanding the biological milieu associated with disease states has important implications for biobehavioral research. Cytokines, signaling molecules that mediate and regulate immunity, inflammation, and hematopoiesis, are an important component of the biological milieu associated with breast cancer. Cytokines have been used as biomarkers in research for prognosis and have been associated with symptoms and adverse outcomes in multiple conditions, including breast cancer. To date, however, the examination of cytokine patterns has been limited by traditional laboratory methods. Advances in proteomic technology now permit the characterization of a broader array of cytokines in a single specimen. Because cytokines operate in integrated networks, a more complete understanding will be gained as multiple cytokines can be examined for patterns of response that may be associated with symptoms and prognosis. Objectives: To use proteomic technology (a) to examine whether there was a difference in cytokine levels and patterns in women with breast cancer compared with controls, (b) to define and compare the receiver operator characteristic curves for standard cytokine classifications, and (c) to identify the best-fitting empirical model of cytokines to distinguish groups of women found to have breast cancer from those with negative biopsies. Methods: The cytokine levels of 35 women who had been diagnosed recently with breast cancer were compared with 24 women with a suspicious breast mass who were found subsequently to have a negative breast biopsy. Multiplex bead array assays permitted the simultaneous measure of multiple markers in a small volume of serum. Nonparametric procedures were used to determine differences in the median values and the distributions for each cytokine. The receiver operator characteristic curves were defined to identify patterns of cytokines. Results: There were significantly higher systemic cytokine values in women with cancer in comparison with those in women without cancer for all cytokines measured, with the exception of granulocyte colony-stimulating factor and interferon-gamma. The only significant associations found between cytokines and age or race were increased levels of interleukin-8 (r = .53) and macrophage inflammatory protein-1&bgr; (r = .45) with increased age in women with a negative biopsy. Three cytokines (granulocyte colony-stimulating factor, interleukin-6, and interleukin-17) distinguished between the breast cancer and no-cancer groups with an exceptionally high areas under the curve (0.981; SE = 0.017). Discussion: Levels of cytokines and their patterns were markedly different in women with breast cancer as compared with those in women who did not have breast cancer. Results from this study highlight the need for further research to examine the levels and patterns of cytokines that may serve as biomarkers in clinical research. Innovations in proteomic technology have implications for expanding biobehavioral research.

Telomere Length: A Review of Methods for Measurement

BackgroundThe exciting discovery that telomere shortening is associated with many health conditions and that telomere lengths can be altered in response to social and environmental exposures has underscored the need for methods to accurately and consistently quantify telomere length. ObjectivesThe purpose of this article is to provide a comprehensive summary that compares and contrasts the current technologies used to assess telomere length. DiscussionMultiple methods have been developed for the study of telomeres. These techniques include quantification of telomere length by terminal restriction fragmentation—which was one of the earliest tools used for length assessment—making it the gold standard in telomere biology. Quantitative polymerase chain reaction provides the advantage of being able to use smaller amounts of DNA, thereby making it amenable to epidemiology studies involving large numbers of people. An alternative method uses fluorescent probes to quantify not only mean telomere lengths but also chromosome-specific telomere lengths; however, the downside of this approach is that it can only be used on mitotically active cells. Additional methods that permit assessment of the length of a subset of chromosome-specific telomeres or the subset of telomeres that demonstrate shortening are also reviewed. ConclusionGiven the increased utility for telomere assessments as a biomarker in physiological, psychological, and biobehavioral research, it is important that investigators become familiar with the methodological nuances of the various procedures used for measuring telomere length. This will ensure that they are empowered to select an optimal assessment approach to meet the needs of their study designs. Gaining a better understanding of the benefits and drawbacks of various measurement techniques is important not only in individual studies, but also to further establish the science of telomere associations with biobehavioral phenomena.

An Integrative Review of Factors Associated with Telomere Length and Implications for Biobehavioral Research

Background:Although telomere shortening occurs as a natural part of aging, there is now a robust body of research that suggests that there is a relationship between psychosocial, environmental, and behavioral factors and changes in telomere length. These factors need to be considered when integrating telomere measurement in biobehavioral research studies. Objectives:This article provides a brief summary of the known facts about telomere biology and an integrative review of current human research studies that assessed relationships between psychosocial, environmental, or behavioral factors and telomere length. Methods:An integrative review was conducted to examine human research studies that focused on psychosocial, environmental, and behavioral factors affecting telomere length and telomerase activity using the electronic databases PubMed/Medline and CINAHL from 2003 to the present. In addition to the known individual factors that are associated with telomere length, the results of the integrative review suggest that perceived stress, childhood adversities, major depressive disorder, educational attainment, physical activity, and sleep duration should also be measured. Discussion:Multiple factors have been shown to affect telomere length. To advance understanding of the role of telomere length in health and disease risk, it will be important to further elucidate the mechanisms that contribute to telomere shortening.

Symptom clusters and quality of life in survivors of ovarian cancer.

Ovarian cancer has nonspecific symptoms, and no screening tool is available for early diagnosis; therefore, only 19% of ovarian cancers are found at an early stage. Given the late diagnosis, women with ovarian cancer often have a prolonged course of treatment and significant morbidity that lasts into survivorship. However, distressing symptoms and their effects on quality of life have been relatively understudied, particularly in survivors of the disease. The purpose of this study was to describe a symptom cluster and its relationship to quality of life in women with ovarian cancer who were recruited from an online cancer support group. Descriptive statistics and hierarchical regression techniques were used to analyze the data obtained from a larger study testing the psychometric properties of a quality-of-life instrument. Most participants had stage III ovarian cancer, and nearly all (97%) had undergone treatment before the study. A symptom cluster composed of depression and fatigue was identified using work by Kim and colleagues [Symptom clusters: concept analysis and clinical implications for cancer nursing. Cancer Nurs. 2005;28(4):270-282]. The symptom cluster explained 41% (P = .000) of the variance in quality of life. These results suggest that fatigue and depression are significant problems for survivors of ovarian cancer.

Association of mitochondrial dysfunction and fatigue: A review of the literature

Fatigue is often described by patients as a lack of energy, mental or physical tiredness, diminished endurance, and prolonged recovery after physical activity. Etiologic mechanisms underlying fatigue are not well understood; however, fatigue is a hallmark symptom of mitochondrial disease, making mitochondrial dysfunction a putative biological mechanism for fatigue. Therefore, this review examined studies that investigated the association of markers of mitochondrial dysfunction with fatigue and proposes possible research directions to enhance understanding of the role of mitochondrial dysfunction in fatigue. A thorough search using PubMed, Scopus, Web of Science, and Embase databases returned 1220 articles. After the application of inclusion and exclusion criteria, a total of 25 articles meeting eligibility criteria were selected for full review. Dysfunctions in the mitochondrial structure, mitochondrial function (mitochondrial enzymes and oxidative/nitrosative stress), mitochondrial energy metabolism (ATP production and fatty acid metabolism), immune response, and genetics were investigated as potential contributors to fatigue. Carnitine was the most investigated mitochondrial function marker. Dysfunctional levels were reported in all the studies investigating carnitine; however, the specific type of carnitine that was dysfunctional varied. Genetic profiles were the second most studied mitochondrial parameter. Six common pathways were proposed: metabolism, energy production, protein transport, mitochondrial morphology, central nervous system dysfunction and post-viral infection. Coenzyme Q10 was the most commonly investigated mitochondrial enzyme. Low levels of Coenzyme Q10 were consistently associated with fatigue. Potential targets for further investigation were identified as well as gaps in the current literature.

Integrated Review of Cytokines in Maternal, Cord, and Newborn Blood: Part I—Associations With Preterm Birth

Preterm birth (PTB; spontaneous delivery prior to 37 weeks gestation) affects one out of eight infants born in the United States and is the most common cause of neonatal morbidity and mortality. Although the pathogenesis of PTB is multifactorial, a growing body of literature supports the hypothesis that one cause of PTB is inflammation in pregnancy. Investigators have implicated mediators of inflammation, most notably proinflammatory cytokines, as being associated with and perhaps a playing a causal role in the pathogenesis of preterm labor and adverse early fetal outcomes. Though researchers have pursued the association of cytokines with preterm labor and subsequent early adverse fetal outcomes as a line of research, there has been little integration of diverse findings across studies. This systematic review appraises the empirical evidence from human studies for the association of levels of cytokines in blood with preterm labor and adverse early fetal outcome to examine the current state of the science in this important area of biobehavioral research. The most consistent finding is that increased levels of proinflammatory cytokines, particularly interleukin (IL) 6, IL-β1, and tumor necrosis factor α (TNF-α), are associated with PTB as compared to levels found at term birth. However, there have been relatively few studies and results have not been consistent. Therefore, further research is needed to elucidate the association of these inflammatory mediators with adverse pregnancy outcomes.

Integrated Review of the Association of Cytokines With Fibromyalgia and Fibromyalgia Core Symptoms

Fibromyalgia (FMS) is a chronic widespread pain (CWP) and fatigue syndrome that affects three to six million adults in the United States. Core symptoms of FMS include pain, fatigue, and mood and sleep disturbances. To date, consensus has not been reached among researchers regarding the pathogenesis of FMS nor the specific role of cytokine activation on the neuroendocrine—immune response patterns in persons with FMS. The purpose of this article is to describe and synthesize the results of research studies focused on the relationship between cytokines and FMS and among cytokines and core symptoms of FMS. There is some support in the literature for relationships among FMS symptoms and cytokines; however, there are discrepant findings related to whether proinflammatory and anti-inflammatory cytokines are elevated or reduced in persons with FMS and whether their levels correlate with the core symptoms of this disorder. Although the use of cytokine biomarkers must be considered exploratory at this time due to the lack of consistent empirical findings, biobehavioral research focused on understanding the relationship of FMS with cytokines may lead to a better understanding of this complex syndrome. This knowledge may ultimately contribute to the development of interventions for symptom management that address not only the symptom manifestation but also a biological mediator of symptoms.

Tryptophan degradation in women with breast cancer: a pilot study

BackgroundAltered tryptophan metabolism and indoleamine 2,3-dioxygenase activity are linked to cancer development and progression. In addition, these biological factors have been associated with the development and severity of neuropsychiatric syndromes, including major depressive disorder. However, this biological mechanism associated with both poor disease outcomes and adverse neuropsychiatric symptoms has received little attention in women with breast cancer. Therefore, a pilot study was undertaken to compare levels of tryptophan and other proteins involved in tryptophan degradation in women with breast cancer to women without cancer, and secondarily, to examine levels in women with breast caner over the course of chemotherapy.FindingsBlood samples were collected from women with a recent diagnosis of breast cancer (n = 33) before their first cycle of chemotherapy and after their last cycle of chemotherapy. The comparison group (n = 24) provided a blood sample prior to breast biopsy. Plasma concentrations of tryptophan, kynurenine, and tyrosine were determined. The kynurenine to tryptophan ratio (KYN/TRP) was used to estimate indoleamine 2,3-dioxygenase activity. On average, the women with breast cancer had lower levels of tryptophan, elevated levels of kynurenine and tyrosine and an increased KYN/TRP ratio compared to women without breast cancer. There was a statistically significant difference between the two groups in the KYN/TRP ratio (p = 0.036), which remained elevated in women with breast cancer throughout the treatment trajectory.ConclusionsThe findings of this pilot study suggest that increased tryptophan degradation may occur in women with early-stage breast cancer. Given the multifactorial consequences of increased tryptophan degradation in cancer outcomes and neuropsychiatric symptom manifestation, this biological mechanism deserves broader attention in women with breast cancer.

Epigenetic Alterations and an Increased Frequency of Micronuclei in Women with Fibromyalgia

Fibromyalgia (FM), characterized by chronic widespread pain, fatigue, and cognitive/mood disturbances, leads to reduced workplace productivity and increased healthcare expenses. To determine if acquired epigenetic/genetic changes are associated with FM, we compared the frequency of spontaneously occurring micronuclei (MN) and genome-wide methylation patterns in women with FM (n = 10) to those seen in comparably aged healthy controls (n = 42 (MN); n = 8 (methylation)). The mean (sd) MN frequency of women with FM (51.4 (21.9)) was significantly higher than that of controls (15.8 (8.5)) (χ 2 = 45.552; df = 1; P = 1.49 × 10−11). Significant differences (n = 69 sites) in methylation patterns were observed between cases and controls considering a 5% false discovery rate. The majority of differentially methylated (DM) sites (91%) were attributable to increased values in the women with FM. The DM sites included significant biological clusters involved in neuron differentiation/nervous system development, skeletal/organ system development, and chromatin compaction. Genes associated with DM sites whose function has particular relevance to FM included BDNF, NAT15, HDAC4, PRKCA, RTN1, and PRKG1. Results support the need for future research to further examine the potential role of epigenetic and acquired chromosomal alterations as a possible biological mechanism underlying FM.