Bradley E. Aouizerat

Abstract

Context To accurately investigate diurnal variations in fatigue, a measure needs to be psychometrically sound and demonstrate stable item function in relationship to time of day. Rasch analysis is a modern psychometric approach that can be used to evaluate these characteristics. Objectives To evaluate, using Rasch analysis, the psychometric properties of the Lee Fatigue Scale (LFS) in a sample of oncology patients. Methods The sample comprised 587 patients (mean age 57.3 ± 11.9 years, 80% women) undergoing chemotherapy for breast, gastrointestinal, gynecological, or lung cancer. Patients completed the 13-item LFS within 30 minutes of awakening (i.e., morning fatigue) and before going to bed (i.e., evening fatigue). Rasch analysis was used to assess validity and reliability. Results In initial analyses of differential item function, eight of the 13 items functioned differently depending on whether the LFS was completed in the morning or in the evening. Subsequent analyses were conducted separately for the morning and evening fatigue assessments. Nine of the morning fatigue items and 10 of the evening fatigue items demonstrated acceptable goodness-of-fit to the Rasch model. Principal components analyses indicated that both morning and evening assessments demonstrated unidimensionality. Person-separation indices indicated that both morning and evening fatigue scales were able to distinguish four distinct strata of fatigue severity. Conclusion Excluding four items from the morning fatigue scale and three items from the evening fatigue scale improved the psychometric properties of the LFS for assessing diurnal variations in fatigue severity in oncology patients.

Abstract

Background: Patients with colorectal cancer (CRC) rarely experience a single symptom associated with their disease and its treatment. Objective: Purpose of this literature review was to summarize the current state of knowledge of multiple co-occurring symptoms in CRC patients who received chemotherapy (CTX) alone or CTX with targeted therapies. Methods: Comprehensive literature search was conducted from 1990 to 2014. These studies were evaluated in terms of the occurrence of multiple co-occurring symptoms in CRC patients who received CTX alone or CTX with targeted therapies; the most common symptom assessment and quality of life (QOL) instruments used; and the associations identified between select demographic and treatment characteristics, QOL, and multiple co-occurring symptoms. Results: Only 5 studies met this review's inclusion criteria. Two studies compared symptoms in patients who received CTX alone or CTX with targeted therapies, and only 1 study reported on symptom occurrence. Of the 5 studies identified, only 2 used the same instrument to assess symptoms, and only 2 studies evaluated for associations between demographic and treatment characteristics and symptom burden, as well as QOL outcomes. Conclusions: Given the larger number of patients with CRC, as well as the increased number of CRC patients who will receive targeted therapies with or without CTX, future studies need to describe the occurrence, severity, and distress of multiple co-occurring symptoms and their impact on CRC patients' QOL. Implications for Practice: To deliver effective symptom management interventions, the most common, severe, and distressing symptoms that CRC patients experience need to be identified.

Abstract

Purpose: Purposes of this study were to identify subgroups of patients with distinct trajectories for morning and evening fatigue, evaluate for differences in demographic and clinical characteristics among these subgroups, and compare and contrast the predictors of subgroup membership for morning and evening fatigue. Methods: Outpatients with breast, gastrointestinal, gynecological, or lung cancer (n = 582) completed questionnaires, a total of six times over two cycles of chemotherapy (CTX). Morning and evening fatigue severity were evaluated using the Lee Fatigue Scale. Latent profile analysis (LPA) was used to identify distinct subgroups. Results: Three latent classes were identified for morning fatigue (i.e., low (31.8 %), high (51.4 %), and very high (16.8 %)) and for evening fatigue (i.e., moderate (20.0 %), high (21.8 %), and very high (58.2 %)). Most of the disease and treatment characteristics did not distinguish among the morning and evening fatigue classes. Compared to the low class, patients in the high and very high morning fatigue classes were younger, had a lower functional status, and higher level of comorbidity. Compared to the moderate class, patients in the very high evening fatigue class were younger, more likely to be female, had child care responsibilities, had a lower functional status, and a higher level of comorbidity. Conclusion: LPA allows for the identification of risk factors for more severe fatigue. Since an overlap was not observed across the morning and evening fatigue classes and unique predictors for morning and evening fatigue were identified, these findings suggest that morning and evening fatigue may have distinct underlying mechanisms.

Abstract

Objectives: The objective of this study was to determine the relationship of serum vitamin D deficiency (VDD) to histologic features of non-alcoholic fatty liver disease (NAFLD), and associated demographic, clinical, laboratory, and transcriptomic data in the well-characterized Non-alcoholic Steatohepatitis Clinical Research Network (NASH CRN) cohort. METHODS: Serum vitamin D 25(OH)D (VD) was quantified by liquid chromatography-tandem mass spectrometry in 190 adults (>18 years) with biopsy-proven NAFLD. Subjects were categorized according to their level of VD as either sufficient (>30 ng/ml), insufficient (≥20≤30 ng/ml), or deficient (VDD; <20 ng/ml). Multivariable logistic regression was used to investigate the association of VDD and the presence of definite NASH and individual histological features of NAFLD after adjusting for age, sex, race, body mass index, alanine aminotransferase, and diabetes status. Hepatic transcriptomic data was compared between VDD and non-VDD subjects. Results: VDD was present in 55% of subjects and was independently associated with definitive NASH (odds ratio (OR) 3.15, 95% confidence interval (CI), 1.62-6.15, P=0.001), increased lobular inflammation (OR=1.98, 95% CI, 1.08-3.61, P=0.026), more ballooning (OR=2.38, 95% CI, 1.32-4.30, P=0.004), and the presence of fibrosis (OR=2.32, 95% CI, 1.13-4.77, P=0.022). There was a significant inverse relationship between lower levels of serum resistin and increased VD level category (P=0.013). The KRT10, SEMA3B, SNORD3C, ARSD, and IGKV4-1 genes were differentially expressed (false discovery rate <0.05) between VDD and non-VDD subjects. Gene ontology and pathway analysis suggest activation of the mitogen-activated protein kinase and nuclear factor-κB pathways in VDD NAFLD subjects. Conclusions: VDD is prevalent among US adult NAFLD patients and is independently associated with a definitive diagnosis of NASH and increased histological severity. Novel associations in proinflammatory pathways were identified, which suggest the mechanism for VDD in the pathogenesis of NASH and support dietary and/or lifestyle modifications to increase vitamin D levels in these patients.

Abstract

Purpose of the research: Evaluate for associations between variations in genes involved in catecholaminergic, gamma-aminobutyric acid (GABA)-ergic, and serotonergic mechanisms of neurotransmission and attentional function latent classes. Patients and methods: This descriptive, longitudinal study was conducted at two radiation therapy departments. The sample included three latent classes of individuals with distinct trajectories of self-reported attentional function during radiation therapy, who were previously identified using growth mixture modeling among 167 oncology patients and 85 of their family caregivers. Multivariable models were used to evaluate for genotypic associations of neurotransmission genes with attentional function latent class membership, after controlling for covariates. Results: Variations in catecholaminergic (i.e., ADRA1D rs4815675, SLC6A3 rs37022), GABAergic (i.e., SLC6A1 rs2697138), and serotonergic (i.e., HTR2A rs2296972, rs9534496) neurotransmission genes were significant predictors of latent class membership in multivariable models. Conclusions: Findings suggest that variations in genes that encode for three distinct but related neurotransmission systems are involved in alterations in attentional function. Knowledge of both phenotypic and genetic markers associated with alterations in attentional function can be used by clinicians to identify patients and family caregivers who are at higher risk for this symptom. Increased understanding of the genetic markers associated with alterations in attentional function may provide insights into the underlying mechanisms for this significant clinical problem.

Abstract

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.

Abstract

Genes involved in circadian regulation, such as circadian locomotor output cycles kaput [CLOCK], cryptochrome [CRY1] and period [PER], have been associated with sleep outcomes in prior animal and human research. However, it is unclear whether polymorphisms in these genes are associated with the sleep disturbances commonly experienced by adults living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Thus, the purpose of this study was to describe polymorphisms in selected circadian genes that are associated with sleep duration or disruption as well as the sleep-wake rhythm strength and phase timing among adults living with HIV/AIDS. A convenience sample of 289 adults with HIV/AIDS was recruited from HIV clinics and community sites in the San Francisco Bay Area. A wrist actigraph was worn for 72 h on weekdays to estimate sleep duration or total sleep time (TST), sleep disruption or percentage of wake after sleep onset (WASO) and several circadian rhythm parameters: mesor, amplitude, the ratio of mesor to amplitude (circadian quotient), and 24-h autocorrelation. Circadian phase measures included clock time for peak activity (acrophase) from actigraphy movement data, and bed time and final wake time from actigraphy and self-report. Genotyping was conducted for polymorphisms in five candidate genes involved in circadian regulation: CLOCK, CRY1, PER1, PER2 and PER3. Demographic and clinical variables were evaluated as potential covariates. Interactions between genotype and HIV variables (i.e. viral load, years since HIV diagnosis) were also evaluated. Controlling for potentially confounding variables (e.g. race, gender, CD4+ T-cell count, waist circumference, medication use, smoking and depressive symptoms), CLOCK was associated with WASO, 24-h autocorrelation and objectively-measured bed time; CRY1 was associated with circadian quotient; PER1 was associated with mesor and self-reported habitual wake time; PER2 was associated with TST, mesor, circadian quotient, 24-h autocorrelation and bed and wake times; PER3 was associated with amplitude, 24-h autocorrelation, acrophase and bed and wake times. Most of the observed associations involved a significant interaction between genotype and HIV. In this chronic illness population, polymorphisms in several circadian genes were associated with measures of sleep disruption and timing. These findings extend the evidence for an association between genetic variability in circadian regulation and sleep outcomes to include the sleep-wake patterns experienced by adults living with HIV/AIDS. These results provide direction for future intervention research related to circadian sleep-wake behavior patterns.

Abstract

Introduction The aims of this study were to compare microRNA (miR) expression between individuals with and without insulin resistance and to determine whether miRs predict response to thiazolidinedione treatment. Materials and methods In a sample of 93 healthy adults, insulin resistance was defined as steady state plasma glucose (SSPG) ≥ 180 mg/dL and insulin sensitive as < 120 mg/dL. Response to thiazolidinedione therapy was defined as ≥ 10% decrease in SSPG. We selected a panel of microRNAs based on prior evidence for a role in insulin or glucose metabolism. Fold change and Wilcoxon rank sum tests were calculated for the 25 miRs measured. Results At baseline, 81% (n = 75) of participants were insulin resistant. Five miRs were differentially expressed between the insulin resistant and sensitive groups: miR-193b (1.45 fold change (FC)), miR-22-3p (1.15 FC), miR-320a (1.36 FC), miR-375 (0.59 FC), and miR-486 (1.21 FC) (all p < 0.05). In the subset who were insulin resistant at baseline and received thiazolidinediones (n = 47), 77% (n = 36) showed improved insulin sensitivity. Six miRs were differentially expressed between responders compared to non-responders: miR-20b-5p (1.20 FC), miR-21-5p, (0.92 FC), miR-214-3p (1.13 FC), miR-22-3p (1.14 FC), miR-320a (0.98 FC), and miR-486-5p (1.25 FC) (all p < 0.05). Discussion This study is the first to report miRs associated with response to a pharmacologic intervention for insulin resistance. MiR-320a and miR-486-5p identified responders to thiazolidinedione therapy among the insulin resistant group.

Abstract

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.

Abstract

Purpose: Anxiety is common among cancer patients and their family caregivers (FCs) and is associated with poorer outcomes. Recently, associations between inflammation and anxiety were identified. However, the relationship between variations in cytokine genes and anxiety warrants investigation. Therefore, phenotypic and genotypic characteristics associated with trait and state anxiety were evaluated in a sample of 167 oncology patients with breast, prostate, lung, or brain cancer and 85 of their FCs. Methods: Using multiple regression analyses, the associations between participants’ demographic and clinical characteristics as well as variations in cytokine genes and trait and state anxiety were evaluated. Results: In the bivariate analyses, a number of phenotypic characteristics were associated with both trait and state anxiety (e.g., age, functional status). However, some associations were specific only to trait anxiety (e.g., number of comorbid conditions) or state anxiety (e.g., participation with a FC). Variations in three cytokine genes (i.e., interleukin (IL) 1 beta, IL1 receptor 2 (IL1R2), nuclear factor kappa beta 2 (NFKB2)) were associated with trait anxiety, and variations in two genes (i.e., IL1R2, tumor necrosis factor alpha (TNFA)) were associated with state anxiety. Conclusions: These findings suggest that both trait and state anxiety need to be assessed in oncology patients and their FCs. Furthermore, variations in cytokine genes may contribute to higher levels of anxiety in oncology patients and their FCs.