Heather Leutwyler

Associations Between Cytokine Genes and a Symptom Cluster of Pain, Fatigue, Sleep Disturbance, and Depression in Patients Prior to Breast Cancer Surgery:

Pain, fatigue, sleep disturbance, and depression are common and frequently co-occurring symptoms in oncology patients. This symptom cluster is often attributed to the release of proinflammatory cytokines. The purposes of this study were to determine whether distinct latent classes of patients with breast cancer (n = 398) could be identified based on their experience with this symptom cluster, whether patients in these latent classes differed on demographic and clinical characteristics and whether variations in cytokine genes were associated with latent class membership. Three distinct latent classes were identified: “all low” (61.0%), “low pain and high fatigue” (31.6%), “all high” (7.1%). Compared to patients in the all low class, patients in the all high class were significantly younger, had less education, were more likely to be non-White, had a lower annual income, were more likely to live alone, had a lower functional status, had a higher comorbidity score, and had more advanced disease. Significant associations were found between interleukin 6 (IL6) rs2069845, IL13 rs1295686, and tumor necrosis factor alpha rs18800610 and latent class membership. Findings suggest that variations in pro- and anti-inflammatory cytokine genes are associated with this symptom cluster in breast cancer patients.

Identification of patient subgroups and risk factors for persistent arm/shoulder pain following breast cancer surgery.

PURPOSE In this prospective, longitudinal study, we extend our findings on persistent breast pain in patients (n = 398) following breast cancer surgery and evaluate the prevalence and characteristics of persistent pain in the arm/shoulder. In addition, differences in the severity of common symptoms and quality of life outcomes measured prior to surgery, among the arm pain classes, were evaluated. METHODS AND SAMPLE Patients were recruited from Breast Care Centers located in a Comprehensive Cancer Center, two public hospitals, and four community practices. Patients were assessed prior to and monthly for six months following breast cancer surgery. RESULTS Using growth mixture modeling, patients were classified into no (41.6%), mild (23.6%), and moderate (34.8%) arm pain classes based on ratings of worst arm/shoulder pain. Compared to the no pain class, patients in the moderate pain class were significantly younger, had a higher body mass index, and were more likely to report preoperative breast pain and swelling in the affected breast. In addition, patients in the moderate pain class reported higher levels of depression, anxiety, and sleep disturbance than the no pain class. CONCLUSIONS Findings suggest that approximately 35% of women experience persistent levels of moderate arm/shoulder pain in the first six months following breast cancer surgery. Moderate arm/shoulder pain is associated with clinically meaningful decrements in functional status and quality of life.

Associations between cytokine gene variations and severe persistent breast pain in women following breast cancer surgery.

UNLABELLED Persistent pain following breast cancer surgery is a significant clinical problem. Although immune mechanisms may play a role in the development and maintenance of persistent pain, few studies have evaluated for associations between persistent breast pain following breast cancer surgery and variations in cytokine genes. In this study, associations between previously identified extreme persistent breast pain phenotypes (ie, no pain vs severe pain) and single nucleotide polymorphisms (SNPs) spanning 15 cytokine genes were evaluated. In unadjusted analyses, the frequency of 13 SNPs and 3 haplotypes in 7 genes differed significantly between the no pain and severe pain classes. After adjustment for preoperative breast pain and the severity of average postoperative pain, 1 SNP (ie, interleukin [IL] 1 receptor 2 rs11674595) and 1 haplotype (ie, IL10 haplotype A8) were associated with pain group membership. These findings suggest a role for cytokine gene polymorphisms in the development of persistent breast pain following breast cancer surgery. PERSPECTIVE This study evaluated for associations between cytokine gene variations and the severity of persistent breast pain in women following breast cancer surgery. Variations in 2 cytokine genes were associated with severe breast pain. The results suggest that cytokines play a role in the development of persistent postsurgical pain.

Associations of Schizophrenia Symptoms and Neurocognition With Physical Activity in Older Adults With Schizophrenia

Background: Low levels of physical activity contribute to the generally poor physical health of older adults with schizophrenia. The associations linking schizophrenia symptoms, neurocognition, and physical activity are not known. Research is needed to identify the reasons for this population’s lack of adequate physical activity before appropriate interventions can be designed and tested. Design and Methods: In this cross-sectional study, 30 adults aged ≥55 years with schizophrenia were assessed on symptoms (Positive and Negative Syndrome Scale), neurocognition (MATRICS Consensus Cognitive Battery), and physical activity (Sensewear ProArmband). Pearson’s bivariate correlations (two-tailed) and univariate linear regression models were used to test the following hypotheses: (1) more severe schizophrenia symptoms are associated with lower levels of physical activity and (2) more severe neurocognitive deficits are associated with lower levels of physical activity. Results: Higher scores on a speed-of-processing test were associated with more average daily steps (p = .002) and more average daily minutes of moderate physical activity (p = .009). Higher scores on a verbal working memory task were associated with more average daily minutes of moderate physical activity (p = .05). More severe depressive symptoms were associated with more average daily minutes of sedentary activity (p = .03). Conclusion: Physical activity interventions for this population are imperative. In order for a physical activity intervention to be successful, it must include components to enhance cognition and diminish psychiatric symptoms.

Cytokine Gene Associations With Self-Report Ratings of Morning and Evening Fatigue in Oncology Patients and Their Family Caregivers

The purpose of this study was to evaluate for differences in variations in pro- and anti-inflammatory cytokine genes between participants who were classified as having low and high levels of morning and evening fatigue and to evaluate for differences in phenotypic characteristics between these two groups. In a sample of 167 oncology outpatients with breast, prostate, lung, or brain cancer and 85 of their family caregivers, growth mixture modeling was used to identify latent classes of individuals based on ratings of morning and evening fatigue obtained prior to, during, and for 4 months following completion of radiation therapy. Differences in single nucleotide polymorphisms and haplotypes in 15 cytokine genes were evaluated between the latent classes. Multiple logistic regression was used to assess the effect of phenotypic and genotypic characteristics on morning and evening fatigue class membership. Associations were found between morning fatigue and number of comorbidities as well as variations in tumor necrosis factor alpha (TNFA) rs1800629 and rs3093662. Evening fatigue was associated with caring for children at home and variations in interleukin 4 (IL4) rs2243248 and TNFA rs2229094. Younger age and lower performance status were associated with both morning and evening fatigue. These findings suggest that inflammatory mediators are associated with the development of morning and evening fatigue. However, because different phenotypic characteristics and genomic markers are associated with diurnal variations in fatigue, morning and evening fatigue may be distinct but related symptoms.

“We’re Not Just Sitting on the Periphery”: A Staff Perspective of Physical Activity in Older Adults With Schizophrenia

UNLABELLED Targeted physical activity interventions to improve the poor physical function of older adults with schizophrenia are necessary but currently not available. Given disordered thought processes and institutionalization, it is likely that older adults with schizophrenia have unique barriers and facilitators to physical activity. It is necessary to consider the perspective of the mental health staff about barriers and facilitators to physical activity to design a feasible intervention. PURPOSE OF THIS STUDY To describe the perceptions of mental health staff about barriers and facilitators to engage in physical activities that promote physical function among older adults with schizophrenia. DESIGN AND METHOD We conducted qualitative interviews with 23 mental health staff that care for older adults with schizophrenia. The data were collected and analyzed with grounded theory methodology. RESULTS The participants were interested in promoting physical activity with older adults with schizophrenia. Facilitators and barriers to physical activity identified were mental health, role models and rewards, institutional factors, and safety. IMPLICATIONS In order to design successful physical activity interventions for this population, the intervention may need to be a routine part of the mental health treatment program and patients may need incentives to participate. Staff should be educated that physical activity may provide the dual benefit of physical and mental health treatment.

Cytokine candidate genes predict the development of secondary lymphedema following breast cancer surgery.

BACKGROUND Lymphedema (LE) is a frequent complication following breast cancer treatment. While progress is being made in the identification of phenotypic risk factors for the development of LE, little information is available on the molecular characterization of LE. The purpose of this study was to determine if variations in pro- and anti-inflammatory cytokine genes were associated with LE following breast cancer treatment. METHODS AND RESULTS Breast cancer patients completed a number of self-report questionnaires. LE was evaluated using bioimpedance spectroscopy. Genotyping was done using a custom genotyping array. No differences were found between patients with (n=155) and without LE (n=387) for the majority of the demographic and clinical characteristics. Patients with LE had a significantly higher body mass index, more advanced disease, and a higher number of lymph nodes removed. Genetic associations were identified for three genes (i.e., interleukin (IL4) 4 (rs2227284), IL 10 (rs1518111), and nuclear kappa factor beta 2 (NFKB2 (rs1056890)) associated with inflammatory responses. CONCLUSIONS These genetic associations suggest a role for a number of pro- and anti-inflammatory genes in the development of LE following breast cancer treatment.

“It’s Good for Me”: Physical Activity in Older Adults with Schizophrenia

Physical activity (PA) interventions to improve the physical function of older adults with schizophrenia are necessary but not available. Older adults with schizophrenia may have unique barriers and facilitators to PA. The purpose of this study was to describe the perceptions of older adults with schizophrenia about barriers and facilitators to engage in physical activities that promote physical function. We conducted qualitative interviews with 16 older adults with schizophrenia. Data were collected and analyzed with grounded theory methodology. Participants expressed interest in becoming more physically active for a variety of perceived benefits including psychiatric symptom management and maintenance of basic function. Key barriers and facilitators to PA emerged in five broad categories: Mental Health, No longer a spring chicken, Pride and Sense of Well-being, Comfort and Safety, and Belonging. Interventions in this population should address negative attitudes towards aging and promote routine physical activities that enhance well-being and companionship.

Differences in morning and evening fatigue in oncology patients and their family caregivers

PURPOSE OF THE RESEARCH To identify distinct latent classes of individuals based on ratings of morning and evening fatigue; evaluate for differences in phenotypic characteristics, as well as symptom and quality of life scores, among these latent classes; and evaluate for an overlap in morning and evening fatigue class membership. PATIENTS AND METHODS In a sample of 167 oncology outpatients and 85 of their FCs, growth mixture modeling was used to identify distinct latent classes based on ratings of morning and evening fatigue obtained before, during, and after radiation therapy. Analyses of variance and Chi Square analyses were used to evaluate for differences among the morning and evening fatigue latent classes. RESULTS Three distinct latent classes for morning fatigue were identified. Participants in the High Morning Fatigue class (47%) were younger and had lower functional status. Three distinct latent classes for evening fatigue were identified. Participants in the High Evening Fatigue class (61%) were younger, more likely to be female, more likely to have children at home, and more likely to be a FC. Only 10.3% of participants were classified in both the Very Low Morning and Low Evening Fatigue classes and 41.3% were classified in both the High Morning and High Evening Fatigue classes. CONCLUSIONS Different characteristics were associated with morning and evening fatigue, which suggests that morning and evening fatigue may be distinct but related symptoms. Additional research is needed to elucidate the mechanisms that may underlie diurnal variability in fatigue.

Variations in potassium channel genes are associated with breast pain in women prior to breast cancer surgery

Abstract Preoperative breast pain in women with breast cancer may result from a number of causes. Previous work from our team found that breast pain occurred in 28.2% of women (n = 398) who were about to undergo breast cancer surgery. The occurrence of preoperative breast pain was associated with a number of demographic and clinical characteristics, as well as variation in two cytokine genes. Given that ion channels regulate excitability of sensory neurons, we hypothesized that variations in potassium channel genes would be associated with preoperative breast pain in these patients. Therefore, in this study, we evaluated for associations between single-nucleotide polymorphisms and inferred haplotypes among 10 potassium channel genes and the occurrence of preoperative breast pain in patients scheduled to undergo breast cancer surgery. Multivariable logistic regression analyses were used to identify those genetic variations that were associated with the occurrence of preoperative breast pain while controlling for age and genomic estimates of and self-reported race/ethnicity. Variations in four potassium channel genes: (1) potassium voltage-gated channel, delayed rectifier, subfamily S, member 1 (KCNS1); (2) potassium inwardly rectifying channel, subfamily J, member 3 (KCNJ3); (3) KCNJ6; and (4) potassium channel, subfamily K, member 9 (KCNK9) were associated with the occurrence of breast pain. Findings from this study warrant replication in an independent sample of women who report breast pain following one or more breast biopsies.