Occurrence and perceived effectiveness of activities used to decrease chemotherapy-induced peripheral neuropathy symptoms in the feet.

PURPOSE: Investigate the reported use and perceived effectiveness of self-care activities for chemotherapy-induced peripheral neuropathy (CIPN) symptoms in the feet. METHODS: Cancer survivors with CIPN (n = 405) completed a questionnaire that assessed the use and perceived effectiveness of 25 self-care activities. Effectiveness was rated on a 0 (not at all) to 10 (completely effective) numeric rating scale. Descriptive statistics and regression analyses were conducted to identify demographic, clinical, and pain characteristics associated with the use and effectiveness of selected self-care activities. RESULTS: The five most commonly used activities were: went for a walk (73.8%); watched television (67.8%); read a book, newspaper or magazine (64.4%); listened to radio, music (60.0%); and did exercises (jogging, swimming) (58.6%). The five most effective self-care activities were: had a trigger point injection (8.3 ( ± 1.3)); took tranquilizers (4.8 ( ± 2.6)); went for ultrasonic stimulation treatment (4.3 ( ± 3.1)); used a heating pad or hot water bottle (4.3 ( ± 2.5)); and used a transcutaneous electric nerve stimulator (4.2 ( ± 2.6)). Demographic, clinical, and pain characteristics influenced use and perceived effectiveness of selected self-care activities to varying degrees. CONCLUSIONS: Two-thirds of the survivors used at least seven self-care activities to manage CIPN symptoms. The most commonly used activities did not receive the highest effectiveness ratings. Some activities that were rated as highly effective warrant more rigorous evaluation. Survivors can try a range of activities to decrease CIPN symptoms in the feet following discussion of their potential risks and benefits with their clinicians.

25-Hydroxycholesterol amplifies microglial IL-1ß production in an apoE isoform-dependent manner.

BACKGROUND: Genome-wide association studies of Alzheimer's disease (AD) have implicated pathways related to lipid homeostasis and innate immunity in AD pathophysiology. However, the exact cellular and chemical mediators of neuroinflammation in AD remain poorly understood. The oxysterol 25-hydroxycholesterol (25-HC) is an important immunomodulator produced by peripheral macrophages with wide-ranging effects on cell signaling and innate immunity. Cholesterol 25-hydroxylase (CH25H), the enzyme responsible for 25-HC production, has also been found to be one of the disease-associated microglial (DAM) genes that are upregulated in the brain of AD and AD transgenic mouse models. METHODS: We used real-time PCR and immunoblotting to examine CH25H expression in human AD brain tissue and in transgenic mouse brain tissue-bearing amyloid-ß plaques or tau pathology. The innate immune response of primary mouse microglia under different treatment conditions or bearing different genetic backgrounds was analyzed using ELISA, western blotting, or immunocytochemistry. RESULTS: We found that CH25H expression is upregulated in human AD brain tissue and in transgenic mouse brain tissue-bearing amyloid-ß plaques or tau pathology. Treatment with the toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS) markedly upregulates CH25H expression in the mouse brain and stimulates CH25H expression and 25-HC secretion in mouse primary microglia. We found that LPS-induced microglial production of the pro-inflammatory cytokine IL-1ß is markedly potentiated by 25-HC and attenuated by the deletion of CH25H. Microglia expressing apolipoprotein E4 (apoE4), a genetic risk factor for AD, produce greater amounts of 25-HC than apoE3-expressing microglia following treatment with LPS. Remarkably, 25-HC treatment results in a greater level of IL-1ß secretion in LPS-activated apoE4-expressing microglia than in apoE2- or apoE3-expressing microglia. Blocking potassium efflux or inhibiting caspase-1 prevents 25-HC-potentiated IL-1ß release in apoE4-expressing microglia, indicating the involvement of caspase-1 inflammasome activity. CONCLUSION: 25-HC may function as a microglial-secreted inflammatory mediator in the brain, promoting IL-1ß-mediated neuroinflammation in an apoE isoform-dependent manner (E4>>E2/E3) and thus may be an important mediator of neuroinflammation in AD.

A longitudinal analysis of phenotypic and symptom characteristics associated with inter-individual variability in employment interference in patients with breast cancer.

PURPOSE: A breast cancer diagnosis has a substantial economic impact. Study aims were to evaluate for inter-individual differences in cancer's level of interference with employment and identify phenotypic and symptom characteristics associated with higher levels of interference. METHODS: Patients (n = 387) were enrolled prior to breast cancer surgery and followed for 12 months. Interference with employment was measured using a 0 (no problem) to 10 (severe problem) numeric rating scale. Hierarchical linear modeling (HLM) was used to evaluate for inter-individual differences in trajectories of employment interference and characteristics associated with employment interference at enrollment and over 12 months. RESULTS: Patients' mean age was 55.0 (±11.7) years and the majority underwent breast conservation surgery (80.6%). Mean employment interference score was 3.2 (±3.7). Unconditional model for employment interference demonstrated a decreasing linear trend (-.076/month). Younger age, lower income, higher pain intensity, and having an axillary lymph node dissection were associated with higher pre-surgical interference scores. Having a sentinel lymph node biopsy was associated with ongoing employment interference scores. Higher sleep disturbance scores were associated with both initial and ongoing employment interference scores. Receipt of chemotherapy, use of complementary or alternative therapies, and re-excision or mastectomy following surgery were significant time varying covariates. CONCLUSION: This study is the first to use HLM to describe inter-individual differences in the trajectories of cancer's interference with employment and associated factors prior to and for 12 months following breast cancer surgery. Patients with the identified risk factors warrant ongoing assessments of employment interference and appropriate referrals.

Trial of SAGE-217 in Patients with Major Depressive Disorder.

BACKGROUND: Altered neurotransmission of γ-aminobutyric acid (GABA) has been implicated in the pathogenesis of depression. Whether SAGE-217, an oral, positive allosteric modulator of GABA type A receptors, is effective and safe for the treatment of major depressive disorder is unknown. METHODS: In this double-blind, phase 2 trial, we enrolled patients with major depression and randomly assigned them in a 1:1 ratio to receive 30 mg of SAGE-217 or placebo once daily. The primary end point was the change from baseline to day 15 in the score on the 17-item Hamilton Depression Rating Scale (HAM-D; scores range from 0 to 52, with higher scores indicating more severe depression). Secondary efficacy end points, which were assessed on days 2 through 8 and on days 15, 21, 28, 35, and 42, included changes from baseline in scores on additional depression and anxiety scales, a reduction from baseline of more than 50% in the HAM-D score, a HAM-D score of 7 or lower, and a Clinical Global Impression of Improvement score of 1 (very much improved) or 2 (much improved) (on a scale of 1 to 7, with a score of 7 indicating that symptoms are very much worse). RESULTS: A total of 89 patients underwent randomization: 45 patients were assigned to the SAGE-217 group, and 44 to the placebo group. The mean baseline HAM-D score was 25.2 in the SAGE-217 group and 25.7 in the placebo group. The least-squares mean (±SE) change in the HAM-D score from baseline to day 15 was -17.4±1.3 points in the SAGE-217 group and -10.3±1.3 points in the placebo group (least-squares mean difference in change, -7.0 points; 95% confidence interval, -10.2 to -3.9; P<0.001). The differences in secondary end points were generally in the same direction as those of the primary end point. There were no serious adverse events. The most common adverse events in the SAGE-217 group were headache, dizziness, nausea, and somnolence. CONCLUSIONS: Administration of SAGE-217 daily for 14 days resulted in a reduction in depressive symptoms at day 15. Adverse events were more common in the SAGE-217 group than in the placebo group. Further trials are needed to determine the durability and safety of SAGE-217 in major depressive disorder and to compare SAGE-217 with available treatments. (Funded by Sage Therapeutics; ClinicalTrials.gov number, NCT03000530.).

Potassium Channel Candidate Genes Predict the Development of Secondary Lymphedema Following Breast Cancer Surgery.

BACKGROUND: Potassium (K) channels play an important role in lymph pump activity, lymph formation, lymph transport, and the functions of lymph nodes. No studies have examined the relationship between K channel candidate genes and the development of secondary lymphedema (LE). OBJECTIVE: The study purpose was to evaluate for differences in genotypic characteristics in women who did (n = 155) or did not (n = 387) develop upper extremity LE following breast cancer treatment based on an analysis of single-nucleotide polymorphisms (SNPs) and haplotypes in 10 K channel genes. METHODS: Upper extremity LE was diagnosed using bioimpedance resistance ratios. Logistic regression analyses were used to identify those SNPs and haplotypes that were associated with LE while controlling for relevant demographic, clinical, and genomic characteristics. RESULTS: Patients with LE had a higher body mass index, had a higher number of lymph nodes removed, had more advanced disease, received adjuvant chemotherapy, received radiation therapy, and were less likely to have undergone a sentinel lymph node biopsy. One SNP in a voltage-gated K channel gene (KCNA1 rs4766311), four in two inward-rectifying K channel genes (KCNJ3 rs1037091 and KCNJ6 rs2211845, rs991985, rs2836019), and one in a two-pore K channel gene (KCNK3 rs1662988) were associated with LE. DISCUSSION: These preliminary findings suggest that K channel genes play a role in the development of secondary LE.

Characteristics associated with inter-individual differences in the trajectories of self-reported attentional function in oncology outpatients receiving chemotherapy.

PURPOSE: Between 14 and 85 % of patients report noticeable changes in cognitive function during chemotherapy (CTX). The purposes of this study were to determine which demographic, clinical, and symptom characteristics were associated with inter-individual variability in initial levels of attentional function as well as with changes in the trajectories of attentional function in a sample of oncology patients who received two cycles of CTX. METHODS: Oncology outpatients (n = 1329) were recruited from two comprehensive cancer centers, one veteran's affairs hospital, and four community-based oncology programs. The Attentional Function Index (AFI) was used to assess perceived effectiveness in completing daily tasks that required working memory and attention. Hierarchical linear modeling (HLM) was used to evaluate for inter-individual variability in initial levels and in the trajectories of attentional function. RESULTS: Demographic, clinical, and symptom characteristics associated with inter-individual differences of attentional function at enrollment (i.e., intercept) were as follows: employment status, functional status, trait anxiety, depressive symptoms, sleep disturbance, evening fatigue, and morning energy. Gender was the only characteristic associated with inter-individual differences in the trajectories of attentional function. Morning fatigue was the only characteristic associated with both initial levels and the trajectories of attentional function. CONCLUSIONS: Prior to their next dose of CTX, patients reported moderate levels of attentional function that persisted over two cycles of CTX. Many of the clinical and symptom characteristics associated with decrements in attentional function are amenable to interventions. Clinicians need to assess patients for changes in attentional function and associated characteristics and recommend evidence-based interventions.

Evidence of associations between cytokine gene polymorphisms and quality of life in patients with cancer and their family caregivers.

PURPOSE/OBJECTIVES: To identify latent classes of individuals with distinct quality-of-life (QOL) trajectories, to evaluate for differences in demographic characteristics between the latent classes, and to evaluate for variations in pro- and anti-inflammatory cytokine genes between the latent classes. DESIGN: Descriptive, longitudinal study. SETTING: Two radiation therapy departments located in a comprehensive cancer center and a community-based oncology program in northern California. SAMPLE: 168 outpatients with prostate, breast, brain, or lung cancer and 85 of their family caregivers (FCs). METHODS: Growth mixture modeling (GMM) was employed to identify latent classes of individuals based on QOL scores measured prior to, during, and for four months following completion of radiation therapy. Single nucleotide polymorphisms (SNPs) and haplotypes in 16 candidate cytokine genes were tested between the latent classes. Logistic regression was used to evaluate the relationships among genotypic and phenotypic characteristics and QOL GMM group membership. MAIN RESEARCH VARIABLES: QOL latent class membership and variations in cytokine genes. FINDINGS: Two latent QOL classes were found: higher and lower. Patients and FCs who were younger, identified with an ethnic minority group, had poorer functional status, or had children living at home were more likely to belong to the lower QOL class. After controlling for significant covariates, between-group differences were found in SNPs in interleukin 1 receptor 2 (IL1R2) and nuclear factor kappa beta 2 (NFKB2). For IL1R2, carrying one or two doses of the rare C allele was associated with decreased odds of belonging to the lower QOL class. For NFKB2, carriers with two doses of the rare G allele were more likely to belong to the lower QOL class. CONCLUSIONS: Unique genetic markers in cytokine genes may partially explain interindividual variability in QOL. IMPLICATIONS FOR NURSING: Determination of high-risk characteristics and unique genetic markers would allow for earlier identification of patients with cancer and FCs at higher risk for poorer QOL. Knowledge of these risk factors could assist in the development of more targeted clinical or supportive care interventions for those identified.

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.

Rapid mood-elevating effects of low field magnetic stimulation in depression.

BACKGROUND: We previously reported rapid mood elevation following an experimental magnetic resonance imaging procedure in depressed patients with bipolar disorder (BPD). This prompted the design, construction, and testing of a portable electromagnetic device that reproduces only the rapidly oscillating (1 kHz, <1 V/m) electromagnetic field of the experimental procedure, called low field magnetic stimulation (LFMS). METHODS: We used a randomized, double blind, sham controlled treatment protocol to study the effects of LFMS in a large group of stably medicated, depressed patients with either BPD (n = 41) or major depressive disorder (n = 22). Subjects received a single, 20-minute treatment. Change in mood was assessed immediately afterward using a visual analog scale (VAS), the 17-item Hamilton Depression Rating Scale (HDRS-17), and the Positive and Negative Affect Schedule scales. RESULTS: Substantial improvement (>10% of baseline) in mood was observed following LFMS treatment relative to sham treatment for both diagnostic subgroups for our primary outcomes, the VAS and the HDRS-17. These differences were not statistically significant in primary analyses stratifying by diagnosis but were significant in secondary analyses combining data across the two diagnostic groups (p = .01 VAS, p = .02 HDRS-17). Rapid improvement in mood was also observed using the Positive and Negative Affect Schedule scales as secondary measures (positive affect scale p = .02 BPD, p = .002 combined group). A finite element method calculation indicates a broad penetration of the LFMS electric field throughout the cerebral cortex. CONCLUSIONS: Low field magnetic stimulation may produce rapid changes in mood using a previously unexplored range of electromagnetic fields.

Timing and sustainability of an exercise intervention in women with breast cancer during and after cancer treatment.

PURPOSE/OBJECTIVES: To compare changes in frequency, duration, and intensity of exercise behaviors over time in women with breast cancer between those who started their exercise intervention at the beginning of chemotherapy (EE) and those who started at the completion of chemotherapy (CE). DESIGN: A secondary data analysis of a randomized, controlled trial for exercise intervention. SETTING: Five cancer centers in the San Francisco Bay Area in California. SAMPLE: 66 outpatient women with breast cancer who were receiving chemotherapy. METHODS: Piecewise linear mixed models analysis was used to study changes in exercise behaviors over time in the EE group during and after treatment. In addition, linear mixed models analysis was used to examine changes between the EE and CE groups after treatment. Participants were in the trial for various length of time (EE group: 19-86 weeks; CE group: 6-43 weeks). MAIN RESEARCH VARIABLES: Exercise frequency, intensity, and duration. FINDINGS: In the EE group, weekly exercise duration increased significantly during treatment (p = 0.02). In addition, weekly exercise intensity increased significantly during treatment (p = 0.02) and decreased significantly after treatment (p = 0.003). After treatment, initial weekly exercise duration was significantly lower in the CE group than in the EE group (p = 0.01). No significant differences existed in frequency and intensity over time between the EE and CE groups. CONCLUSIONS: Women with breast cancer can sustain exercise behaviors when they start an exercise intervention in the beginning of chemotherapy treatment. IMPLICATIONS FOR NURSING: Strategies to support patients in maintaining their exercise habit may be needed during the post-treatment period.

The relationship between hope and pain in a sample of hospitalized oncology patients.

OBJECTIVE: The aims of this study were to describe hope in a sample of hospitalized oncology patients in pain and to determine if various demographic, clinical, and pain characteristics were related to hope. In addition, the individual item and total Herth Hope Index (HHI) scores for these oncology inpatients with pain were compared with those from the general Norwegian population. METHOD: Oncology inpatients in pain (n = 225) were recruited from the Norwegian Radium Hospital. The research instruments included the HHI, the Brief Pain Inventory (BPI), and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Data were analyzed using descriptive statistics, Pearson's correlations, and one-sample t tests. RESULTS: Total HHI scores in oncology inpatients with pain were comparable to a similar sample in Taiwan. The Norwegian oncology inpatients reported significantly higher total HHI scores than the general Norwegian population. The largest difference was on the item "I feel scared about my future." No relationships were found between total HHI scores and any of the pain intensity scores. Significant relationships were found between total HHI scores and the more psychosocial interference items on BPI and sleep. SIGNIFICANCE OF RESULTS: The higher levels of hope in the oncology inpatients with pain compared with the general Norwegian population may reflect a "response shift" in the patients' evaluation of hope. Although the difference is relatively small, it may represent a clinically meaningful difference. The fact that significant relationships were found between HHI scores and the more psychosocial interference scores on BPI suggest that hope may be more related to psychosocial effects on pain than on its physical effects.

Children's expectations of pain, perceptions of analgesic efficacy, and experiences with nonpharmacologic pain management strategies at home following tonsillectomy.

PURPOSE: To document children's (ages 6-15 years) descriptions of their pain management at home following tonsillectomy. DESIGN AND METHODS: Audio-taped interviews of 80 children were transcribed and coded. Data for each response category were tabulated. RESULTS: Children reported they had more pain after surgery than expected, the pain medicine helped to take their pain away, taking the pain medicine was associated with a negative response by some children, and cold liquids/food by mouth provided pain relief. PRACTICE IMPLICATIONS: Findings provide insight into children's perspective of pain management at home following tonsillectomy and methods for relieving their pain.

Effect of docosahexaenoic acid on lipoprotein subclasses in hyperlipidemic children (the EARLY study).

To test the hypothesis that a dietary omega-3 fatty acid, docosahexaenoic acid, improves the lipoprotein subclass profile of children who have hyperlipidemia, we conducted a randomized, double-blind, placebo-controlled study. Children who had hyperlipidemia (n = 20) were stabilized on a low-fat diet for 6 weeks and then randomized to receive 1.2 g/day of docosahexaenoic acid for 6 weeks or placebo. Supplementation with docosahexaenoic acid significantly increased low-density lipoprotein subclass 1 and high-density lipoprotein subclass 2 (large and buoyant; less atherogenic particles) by 91% and 14%, respectively, compared with the placebo phase. Low-density lipoprotein subclass 3 (small and dense; more atherogenic particles) decreased by 48%.