Bradley E. Aouizerat

Abstract

Context: Fatigue and sleep disturbance are common problems in oncology patients and their family caregivers (FCs). However, little is known about factors that contribute to interindividual variability in these symptoms or to their underlying biologic mechanisms. Objectives: An evaluation was done on whether genetic variation in a prominent proinflammatory cytokine, interleukin-6 (IL-6 c.-6101A>T [rs4719714]), was associated with mean ratings of evening fatigue, morning fatigue, and sleep disturbance, as well as with the trajectories of these symptoms. Methods: Over six months, participants completed standardized measures of fatigue and sleep disturbance. Linear regression was used to assess the effect of the IL-6 genotype and other covariates on mean fatigue and sleep disturbance scores. Hierarchical linear modeling was used to determine the effect of the IL-6 genotype on symptom trajectories. Results: Common allele homozygotes reported higher levels of evening fatigue (P = 0.003), morning fatigue (P = 0.09), and sleep disturbance (P = 0.003) than minor allele carriers. Predictors of baseline level and trajectories of evening fatigue included age, gender, and genotype (intercepts) and baseline level of evening fatigue (slope). Predictors of baseline level and trajectories of morning fatigue included age and genotype (intercept) and age and baseline level of morning fatigue (slope). Predictors of baseline level and trajectories of sleep disturbance included age and genotype (intercept) and baseline level of sleep disturbance (slope). Conclusions: Findings provide preliminary evidence of a genetic association between a functional promoter polymorphism in the IL-6 gene and severity of evening fatigue, morning fatigue, and sleep disturbance in oncology patients and their FCs.

Abstract

Aims/hypothesis: The aim of this study was to define the prevalence of the metabolic syndrome and its component risk factors among individuals of South Asian origin living in the United States. Methods: We analyzed baseline data from 1,445 participants enrolled in a cohort study investigating risk factors for cardiovascular disease in South Asians. We defined the metabolic syndrome using the International Diabetes Federation criteria for waist circumference (>90cm for men; >80cm, women), triglycerides (>150mg/dL), high-density lipoprotein cholesterol (HDL-C) (<40mg/dL (men), <45mg/dL (women)), blood pressure (>135/80mmHg), and fasting glucose (>100mg/dL). Results: The mean age was 43±10 years, and 30% of participants were women. The prevalence of metabolic syndrome was 27% (31% men vs. 17% women, P<0.05). Fifty-nine percent of the cohort had high waist circumference (58% men vs. 62% women, P = not significant [N.S.]), 47% had low HDL-C [46% men vs. 48% women (NS)], 19% had elevated triglycerides (23% men vs. 8% women, P<0.05), 14% had hypertension (16% men vs. 9% women, P< 0.05), and 13% had elevated fasting glucose (18% men vs. 11% women, P<0.05). The most common metabolic syndrome phenotype is low HDL-C with elevated triglycerides. Conclusions: Although the prevalence of the metabolic syndrome is lower than previous reports of South Asians, the prevalence is still unacceptably high despite the presence of protective demographic factors.

Abstract

Purpose of the research: The purpose of this study was to describe the occurrence of significant mood disturbance and evaluate for differences in sleep quality among four mood groups (i.e., neither anxiety nor depression, only anxiety, only depression, anxiety and depression) prior to the initiation of radiation therapy (RT). Methods and sample: Patients (n=179) with breast, prostate, lung, and brain cancer were evaluated prior to the initiation of RT using the Pittsburgh Sleep Quality Index (PSQI), the Center for Epidemiological Studies Depression Scale, and the Spielberger State Anxiety Inventory. Differences in sleep disturbance among the four mood groups were evaluated using analyses of variance. Key results: While 38% of the patients reported some type of mood disturbance, 57% of the patients reported sleep disturbance. Patients with clinically significant levels of anxiety and depression reported the highest levels of sleep disturbance. Conclusions: Overall, oncology patients with mood disturbances reported more sleep disturbance than those without mood disturbance. Findings suggest that oncology patients need to be assessed for mood and sleep disturbances.

Abstract

Studies suggest that people living with HIV (PLWH) experience many unrelieved symptoms. The purpose of this study was to estimate the occurrence of pain in adult PLWH and to determine whether participants with pain differed from those without pain on selected demographic factors, clinical characteristics, symptoms of fatigue, sleep disturbance, anxiety, or depression. The authors conducted a descriptive, comparative, and correlational study of 317 PLWH seen at academic and community clinics in San Francisco. Participants completed a demographic questionnaire, the Memorial Symptom Assessment Scale, the Fatigue Severity Scale, the General Sleep Disturbance Scale, the Profile of Moods State Tension-Anxiety subscale, and the Center for Epidemiological Studies-Depression Scale. Clinical characteristics (i.e., disease and treatment information) were obtained by self-report. A single item on pain from the Memorial Symptom Assessment Scale was used to classify participants into those with and without pain. Pain was highly prevalent (55%) and was associated with immune status (CD4+ T-cell count), race, and sleep disturbance, but not with age, gender, or symptoms of fatigue, depression, or anxiety.

Abstract

BACKGROUND: Data on the quality of life (QOL) of children with non-alcoholic fatty liver disease (NAFLD) are needed to estimate the true burden of illness in children with NAFLD.AIM: To characterize QOL and symptoms of children with NAFLD and to compare QOL in children with NAFLD with that in a sample of healthy children.METHODS: Quality of life and symptoms were assessed in children with biopsy-proven NAFLD enrolled in the NASH Clinical Research Network. PedsQL scores were compared with scores from healthy children. For children with NAFLD, between-group comparisons were made to test associations of demography, histological severity, symptoms and QOL.RESULTS: A total of 239 children (mean age 12.6 years) were studied. Children with NAFLD had worse total (72.8 vs. 83.8, P < 0.01), physical (77.2 vs. 87.5, P < 0.01) and psychosocial health (70.4 vs. 81.9, P < 0.01) scores compared with healthy children. QOL scores did not significantly differ by histological severity of NAFLD. Fatigue, trouble sleeping and sadness accounted for almost half of the variance in QOL scores. Impaired QOL was present in 39% of children with NAFLD.CONCLUSIONS: Children with NAFLD have a decrement in QOL. Symptoms were a major determinant of this impairment. Interventions are needed to restore and optimize QOL in children with NAFLD.

Abstract

Background: Fatigue is a significant problem associated with radiation therapy (RT). Objective: This study examined how evening and morning fatigue changed from the time of simulation to 4 months after the completion of RT and investigated whether specific demographic and disease characteristics and baseline severity of symptoms predicted the initial levels of fatigue and characteristics of the trajectories of fatigue. Methods: Seventy-three women with breast cancer completed questionnaires that assessed sleep disturbance, depression, anxiety, and pain prior to the initiation of RT and the Lee Fatigue Scale, over 6 months. Descriptive statistics and hierarchical linear modeling were used for data analysis. Results: Large amounts of interindividual variability were found in the trajectories of fatigue. Evening fatigue at baseline was negatively influenced by having children at home and depression. The trajectory of evening fatigue was worse for women who were employed. Morning fatigue at baseline was influenced by younger age, lower body mass index, and the degree of sleep disturbance and trait anxiety. Trajectories of morning fatigue were worse for patients with a higher disease stage and more medical comorbidities. Conclusion: Interindividual and diurnal variability in fatigue found in women with breast cancer is similar to that found in men with prostate cancer. However, the predictors of interindividual variability in fatigue between these 2 cohorts were different. Implications for Practice: Diurnal variability and different predictors for morning and evening fatigue suggest different underlying mechanisms. The various predictors of fatigue need to be considered in the design of future intervention studies.

Abstract

BACKGROUND: Whether triglyceride-mediated pathways are causally relevant to coronary heart disease is uncertain. We studied a genetic variant that regulates triglyceride concentration to help judge likelihood of causality.METHODS: We assessed the -1131T>C (rs662799) promoter polymorphism of the apolipoprotein A5 (APOA5) gene in relation to triglyceride concentration, several other risk factors, and risk of coronary heart disease. We compared disease risk for genetically-raised triglyceride concentration (20,842 patients with coronary heart disease, 35,206 controls) with that recorded for equivalent differences in circulating triglyceride concentration in prospective studies (302 430 participants with no history of cardiovascular disease; 12,785 incident cases of coronary heart disease during 2.79 million person-years at risk). We analysed -1131T>C in 1795 people without a history of cardiovascular disease who had information about lipoprotein concentration and diameter obtained by nuclear magnetic resonance spectroscopy.FINDINGS: The minor allele frequency of -1131T>C was 8% (95% CI 7-9). -1131T>C was not significantly associated with several non-lipid risk factors or LDL cholesterol, and it was modestly associated with lower HDL cholesterol (mean difference per C allele 3.5% [95% CI 2.6-4.6]; 0.053 mmol/L [0.039-0.068]), lower apolipoprotein AI (1.3% [0.3-2.3]; 0.023 g/L [0.005-0.041]), and higher apolipoprotein B (3.2% [1.3-5.1]; 0.027 g/L [0.011-0.043]). By contrast, for every C allele inherited, mean triglyceride concentration was 16.0% (95% CI 12.9-18.7), or 0.25 mmol/L (0.20-0.29), higher (p=4.4x10(-24)). The odds ratio for coronary heart disease was 1.18 (95% CI 1.11-1.26; p=2.6x10(-7)) per C allele, which was concordant with the hazard ratio of 1.10 (95% CI 1.08-1.12) per 16% higher triglyceride concentration recorded in prospective studies. -1131T>C was significantly associated with higher VLDL particle concentration (mean difference per C allele 12.2 nmol/L [95% CI 7.7-16.7]; p=9.3x10(-8)) and smaller HDL particle size (0.14 nm [0.08-0.20]; p=7.0x10(-5)), factors that could mediate the effects of triglyceride.INTERPRETATION: These data are consistent with a causal association between triglyceride-mediated pathways and coronary heart disease.FUNDING: British Heart Foundation, UK Medical Research Council, Novartis.

Abstract

Objectives: To investigate the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene as a potential modifier gene for coronary heart disease (CHD) in patients with familial hypercholesterolemia (FH). Background: The ALOX5AP gene is required for the synthesis of leukotrienes, a protein family involved in inflammatory responses. Recently, genetic variation in this gene was shown to be associated with myocardial infarction in an Icelandic and British population. Since FH is characterized by severely increased levels of plasma low-density lipoprotein (LDL) cholesterol levels, chronic inflammation of the arterial wall, and subsequent premature CHD, the ALOX5AP gene could be an important modifier gene for CHD in FH. Methods: In a cohort of 1817 FH patients, we reconstructed two four-marker haplotypes, previously defined in Icelandic (HapA) and British (HapB) individuals. The haplotypes were inferred with PHASE and the associations between the haplotypes and CHD were analyzed with a Cox proportional hazards model, adjusted for year of birth, sex, and smoking. Results: HapB had a frequency of 6.9% and 8.2% in the group without and with CHD, respectively, conferring a hazard ratio of 1.48 (95% CI 1.17-1.89, p = 0.001). This association was predominantly found in patients with LDL cholesterol levels above the median (HR 1.82, 95% CI 1.20-2.76, p = 0.005). HapA was not associated with CHD. Conclusion: We conclude that genetic variation in the ALOX5AP gene contributes to CHD risk in patients with FH. Our findings emphasize the important role of inflammation in the pathogenesis of early CHD in this disorder, particularly in patients with more severely raised LDL cholesterol levels.

Abstract

Background: Transforming growth factor ß (TGFß) signaling has been shown to promote myocardial fibrosis and remodeling with coronary artery disease (CAD), and previous studies show a major role for fibrosis in the initiation of malignant ventricular arrhythmias (VA) and sudden cardiac arrest (SCA). Common single nucleotide polymorphisms (SNPs) in TGFß pathway genes may be associated with SCA. Objective: We examined the association of common SNPs among 12 candidate genes in the TGFß pathway with the risk of SCA. Methods: SNPs (n = 617) were genotyped in a case-control study comparing 89 patients with CAD and SCA caused by VA to 520 healthy control subjects. Results: Nineteen SNPs among 5 genes (TGFB2, TGFBR2, SMAD1, SMAD3, SMAD6) were associated with SCA after adjustment for age and sex. After permutation analysis to account for multiple testing, a single SNP in TGFBR2 (rs9838682) was associated with SCA (odds ratio: 1.66, 95% confidence interval: 1.08 to 2.54, P = .02). Conclusion: We show an association between a common TGFBR2 polymorphism and risk of SCA caused by VA in the setting of CAD. If validated, these findings support the role of genetic variation in TGFß signaling in SCA susceptibility.

Abstract

Goals of work: The goals of the study were to determine the occurrence rates for and the severity of symptoms at the middle, end, and 1 month after the completion of radiation therapy (RT), to determine the number and types of symptom clusters at these three time points, and to evaluate for changes over time in these symptom clusters. Materials and methods: Symptom occurrence and severity were evaluated using the Memorial Symptom Assessment Scale (MSAS) in a sample of patients (n∈=∈160) who underwent RT for breast or prostate cancer. At each time point, an exploratory factor analysis was done to determine the number of symptom clusters (i.e., symptom factors) based on the MSAS symptom severity ratings. Main results: The majority of the patients were male and married with a mean age of 61.1 years. The five symptoms with the highest occurrence rates across all three time points were lack of energy, pain, difficulty sleeping, feeling drowsy, and sweats. Although the number of symptoms and the specific symptoms within each symptom cluster were not identical across the three time points, three relatively similar symptom clusters (i.e., "mood-cognitive" symptom cluster, "sickness-behavior" symptom cluster, "treatment-related", or "pain" symptom cluster) were identified in this sample. The internal consistency coefficients for the mood-cognitive symptom cluster and sickness-behavior symptom cluster were adequate at ≥ 0.68. Conclusions: Three relatively stable symptom clusters were found across RT. The majority of the symptom cluster severity scores were significantly higher in patients with breast cancer compared to patients with prostate cancer.