Bradley E. Aouizerat

Abstract

Purpose: Depressive symptoms are common in cancer patients and their family caregivers (FCs). While these symptoms are characterized by substantial interindividual variability, the factors that predict this variability remain largely unknown. This study sought to confirm latent classes of oncology patients and FCs with distinct depressive symptom trajectories and to examine differences in phenotypic and genotypic characteristics among these classes. Method: Among 167 oncology outpatients with breast, prostate, lung, or brain cancer and 85 of their FCs, growth mixture modeling (GMM) was used to identify latent classes of individuals based on Center for Epidemiological Studies-Depression (CES-D) scores obtained prior to, during, and for four months following completion of radiation therapy. One hundred four single nucleotide polymorphisms (SNPs) and haplotypes in 15 candidate cytokine genes were interrogated for differences between the two largest latent classes. Multivariate logistic regression analyses assessed effects of phenotypic and genotypic characteristics on class membership. Results: Four latent classes were confirmed: Resilient (56.3%), Subsyndromal (32.5%), Delayed (5.2%), and Peak (6.0%). Participants who were younger, female, non-white, and who reported higher baseline trait and state anxiety were more likely to be in the Subsyndromal, Delayed, or Peak groups. Variation in three cytokine genes (i.e., interleukin 1 receptor 2 [IL1R2], IL10, tumor necrosis factor alpha [TNFA]), age, and performance status predicted membership in the Resilient versus Subsyndromal classes. Conclusions: Findings confirm the four latent classes of depressive symptom trajectories previously identified in a sample of breast cancer patients. Variations in cytokine genes may influence variability in depressive symptom trajectories.

Abstract

Purpose of the research: Little is known about the relationships between pain, anxiety, and depression in women prior to breast cancer surgery. The purpose of this study was to evaluate for differences in anxiety, depression, and quality of life (QOL) in women who did and did not report the occurrence of breast pain prior to breast cancer surgery. We hypothesized that women with pain would report higher levels of anxiety and depression as well as poorer QOL than women without pain. Methods and sample: A total of 390 women completed self-report measures of pain, anxiety depression, and QOL prior to surgery. Key results: Women with preoperative breast pain (28%) were significantly younger, had a lower functional status score, were more likely to be Non-white and to have gone through menopause. Over 37% of the sample reported clinically meaningful levels of depressive symptoms. Almost 70% of the sample reported clinically meaningful levels of anxiety. Patients with preoperative breast pain reported significantly higher depression scores and significantly lower physical well-being scores. No between group differences were found for patients' ratings of state and trait anxiety or total QOL scores. Conclusions: Our a priori hypotheses were only partially supported. Findings from this study suggest that, regardless of pain status, anxiety and depression are common problems in women prior to breast cancer surgery.

Abstract

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.

Abstract

The purpose of this study was to evaluate for differences in occurrence and severity ratings of sleep disturbance, fatigue, and decreased energy in women who reported breast pain prior to surgery for breast cancer. Of the 390 women who completed self-report measures for each symptom, 28.2% reported pain in their breast prior to surgery. A higher percentage of women in the pain group (i.e., 66.7% versus 53.5%) reported clinically meaningful levels of sleep disturbance. However, no between group differences were found in the severity of sleep disturbance, fatigue, or decreased energy. Findings from this study suggest that sleep disturbance, fatigue, and decreased levels of energy are significant problems for women prior to breast cancer surgery. Future studies need to evaluate for specific characteristics that place women at greater risk for these symptoms as well as the mechanisms that underlie these symptoms.

Abstract

Background: Mortality rates for cancer are decreasing in patients under 60 and increasing in those over 60 years of age. The reasons for these differences in mortality rates remain poorly understood. One explanation may be that older patients received substandard treatment because of concerns about adverse effects. Given the paucity of research on the multiple dimensions of the symptom experience in older oncology patients, the purpose of this study was to evaluate for differences in ratings of symptom occurrence, severity, frequency, and distress between younger (< 60 years) and older ( ≥ 60 years) adults undergoing cancer treatment. We hypothesized that older patients would have significantly lower ratings on four symptom dimensions.Methods: Data from two studies in the United States and one study in Australia were combined to conduct this analysis. All three studies used the MSAS to evaluate the occurrence, severity, frequency, and distress of 32 symptoms.Results: Data from 593 oncology outpatients receiving active treatment for their cancer (i.e., 44.4% were < 60 years and 55.6% were ≥ 60 years of age) were evaluated. Of the 32 MSAS symptoms, after controlling for significant covariates, older patients reported significantly lower occurrence rates for 15 (46.9%) symptoms, lower severity ratings for 6 (18.9%) symptoms, lower frequency ratings for 4 (12.5%) symptoms, and lower distress ratings for 14 (43.8%) symptoms.Conclusions: This study is the first to evaluate for differences in multiple dimensions of symptom experience in older oncology patients. For almost 50% of the MSAS symptoms, older patients reported significantly lower occurrence rates. While fewer age-related differences were found in ratings of symptom severity, frequency, and distress, a similar pattern was found across all three dimensions. Future research needs to focus on a detailed evaluation of patient and clinical characteristics (i.e., type and dose of treatment) that explain the differences in symptom experience identified in this study.

Abstract

Epigenetic mechanisms provide an adaptive layer of control in the regulation of gene expression that enables an organism to adjust to a changing environment. Epigenetic regulation increases the functional complexity of deoxyribonucleic acid (DNA) by altering chromatin structure, nuclear organization, and transcript stability. These changes may additively or synergistically influence gene expression and result in long-term molecular and functional consequences independent of the DNA sequence that may ultimately define an individual's phenotype. This article (1) describes histone modification, DNA methylation, and expression of small noncoding RNA species; (2) reviews the most common methods used to measure these epigenetic changes; and (3) presents factors that need to be considered when choosing a specific tissue to evaluate for epigenetic changes.

Abstract

AIMS:: Fish and ω-3 fatty acids are reported to be beneficial in pediatric nonalcoholic fatty liver disease (NAFLD), but no studies have assessed their relation to histological severity. The objectives of this study were to evaluate the dietary intake of fish and ω-3 fatty acids in children with biopsy-proven NAFLD, and examine their association with serological and histological indicators of disease. METHODS:: This was a cross-sectional analysis of 223 children (6-18 years) who participated in the Treatment of Nonalcoholic Fatty Liver Disease in Children trial or the NAFLD Database study conducted by the Nonalcoholic Steatohepatitis Clinical Research Network. The distribution of fish and ω-3 fatty acid intake was determined from responses to the Block Brief 2000 Food Frequency Questionnaire, and analyzed for associations with serum alanine aminotransferase, histological features of fatty liver disease, and diagnosis of steatohepatitis after adjusting for demographic, anthropometric, and dietary variables. RESULTS:: The minority of subjects consumed the recommended 8 ounces of fish per week (22/223 [10%]) and 200 mg of long-chain ω-3 fatty acids per day (12/223 [5%]). Lack of fish and long-chain ω-3 fatty acid intake was associated with greater portal (P=0.03 and P=0.10, respectively) and lobular inflammation (P=0.09 and P=0.004, respectively) after controlling for potential confounders. CONCLUSIONS:: Fish and ω-3 fatty acid intake was insufficient in children with NAFLD, which may increase susceptibility to hepatic inflammation. Patients with pediatric NAFLD should be encouraged to consume the recommended amount of fish per week.

Abstract

OBJECTIVE: HIV infection and illicit drug use are each associated with diminished cognitive performance. This study examined the separate and interactive effects of HIV and recent illicit drug use on verbal memory, processing speed, and executive function in the multicenter Women's Interagency HIV Study. METHODS: Participants included 952 HIV-infected and 443 HIV-uninfected women (mean age = 42.8, 64% African-American). Outcome measures included the Hopkins Verbal Learning Test - Revised and the Stroop test. Three drug use groups were compared: recent illicit drug users (cocaine or heroin use in past 6 months, n = 140), former users (lifetime cocaine or heroin use but not in past 6 months, n = 651), and nonusers (no lifetime use of cocaine or heroin, n = 604). RESULTS: The typical pattern of recent drug use was daily or weekly smoking of crack cocaine. HIV infection and recent illicit drug use were each associated with worse verbal learning and memory (P < 0.05). Importantly, there was an interaction between HIV serostatus and recent illicit drug use such that recent illicit drug use (compared with nonuse) negatively impacted verbal learning and memory only in HIV-infected women (P < 0.01). There was no interaction between HIV serostatus and illicit drug use on processing speed or executive function on the Stroop test. CONCLUSIONS: The interaction between HIV serostatus and recent illicit drug use on verbal learning and memory suggests a potential synergistic neurotoxicity that may affect the neural circuitry underlying performance on these tasks.

Abstract

OBJECTIVE: The Met allele of the catechol-O-methyltransferase (COMT) Val158Met polymorphism is associated with increased cortical dopamine and risk behaviors including illicit drug use and unprotected sex. Therefore, we examined whether or not the distribution of the Val158Met genotype differed between HIV-infected and HIV-uninfected women. DESIGN: Cross-sectional analysis using data from the Women's Interagency HIV Study (WIHS), the largest longitudinal cohort study of HIV in women. METHODS: We conducted an Armitage-Cochran test and logistic regression to compare genotype frequencies between 1848 HIV-infected and 612 HIV-uninfected women in WIHS. RESULTS: The likelihood of carrying one or two Met alleles was greater in HIV-infected women (61%) compared to HIV-uninfected women (54%), Z = -3.60, P <0.001. CONCLUSION: We report the novel finding of an association between the Val158Met genotype and HIV serostatus that may be mediated through the impact of dopamine function on propensity for risk-taking.

Abstract

Proteinuria is associated with adverse clinical outcomes in HIV infection. Here we evaluated whether APOL1 risk alleles, previously associated with advanced kidney disease, are independently associated with proteinuria in HIV infection in a cross-sectional study of HIV-infected women in the Women's Interagency HIV Study. We estimated the percent difference in urine protein excretion and odds of proteinuria (≥200 mg/g) associated with two versus one or no APOL1 risk allele using linear and logistic regression, respectively. Of 1285 women successfully genotyped, 379 carried one and 80 carried two risk alleles. Proteinuria was present in 124 women, 78 of whom had proteinuria confirmed on a second sample. In women without prior AIDS, two risk alleles were independently associated with a 69% higher urine protein excretion (95% confidence interval (CI): 36, 108) and five-fold higher odds of proteinuria (95% CI: 2.45, 10.37) as compared with one or no risk allele. No association was found in women with prior AIDS. Analyses in which women with impaired kidney function were excluded and proteinuria was confirmed by a second urine sample yielded similar estimates. Thus, APOL1 risk alleles are associated with significant proteinuria in HIV-infected persons without prior clinical AIDS, independent of clinical factors traditionally associated with proteinuria. Trials are needed to determine whether APOL1 genotyping identifies individuals who could benefit from earlier intervention to prevent overt renal disease.