Faculty Bibliography

PURPOSE: This study compared the occurrence rates for and severity ratings of sleep disturbance in patient-family caregiver (FC) dyads. PATIENTS AND METHODS: In total, 102 dyads were recruited from two radiation therapy (RT) departments. Patients and their FCs completed the Pittsburgh Sleep Quality Index (PSQI) and the General Sleep Disturbance Scale (GSDS) and wore wrist actigraphs to obtain subjective and objective measures of the occurrence and severity of sleep disturbance at the initiation of RT. Match paired t tests were used to evaluate for dyadic differences. RESULTS: No differences were found in the occurrence of clinically significant levels of sleep disturbance between patients and their FCs that ranged between 40% and 50% using subjective and objective measures. Few differences were found in the severity of any of the sleep-wake parameters between patients and FCs using both the subjective and objective measures of sleep disturbance. CONCLUSION: The findings from this study suggest that patients with cancer and their FCs experience similar levels of sleep disturbance and that both groups could benefit from interventions that aim to promote restful sleep. In addition to routine and systematic assessment of sleep disturbance by oncology clinicians, interventions are needed that take into account the specific needs of the patient and the FC as well as the potential for partners' sleep patterns to influence one another.

Though pursuit of host genetic factors that influence the pathogenesis of HIV began over two decades ago, progress has been slow. Initial genome-level searches for variations associated with HIV-related traits have yielded interesting candidates, but less in the way of novel pathways to be exploited for therapeutic targets. More recent genome-wide association studies (GWAS) that include different phenotypes, novel designs, and that have examined different population characteristics suggest novel targets and affirm the utility of additional searches. Recent findings from these GWAS are reviewed, new directions for research are identified, and the promise of systems biology to yield novel insights is discussed.

To date, no studies have evaluated for differences in subjective and objective measures of sleep disturbance in oncology outpatients with and without pain. This descriptive study, recruited 182 patients from 2 radiation therapy (RT) departments at the time of the patient's simulation visit. Approximately 38% of the sample reported moderate to severe pain (ie, worst pain intensity of 6.2 +/- 2.4). After controlling for age, patients in pain reported worse sleep quality and more sleep disturbance using the Pittsburgh Sleep Quality Index. With the General Sleep Disturbance Scale, patients in pain reported poorer sleep quality, increased use of sleep medications, and more daytime sleepiness. In addition using an objective measure of sleep disturbance (ie, actigraphy), significant gender x pain interactions were found for sleep onset latency, percentage of time awake at night, wake duration, total sleep time, and sleep efficiency. While no differences were found in female patients, males in pain had worse scores than males without pain. Findings from this study suggest that pain and sleep disturbance are prevalent in oncology outpatients and that a patient's age and gender need to be considered in any evaluation of the relationship between pain and sleep. PERSPECTIVE: The effects of pain on subjective and objective sleep parameters appear to be influenced by both patients' age and gender.

OBJECTIVE: The findings from several studies suggest that palliative care patients with advanced cancer experience multiple symptoms, and that these symptoms may be related to demographic and clinical factors as well as to patient outcomes. However, no systematic review has summarized the findings from studies that assessed multiple symptoms, predictors, and outcomes in these patients. The purposes of this review, focused on palliative care patients with advanced cancer, are to: 1) describe the relationships among multiple symptoms; 2) describe the predictors of multiple symptoms; and 3) describe the relationships between multiple symptoms and patient outcomes. METHOD: Comprehensive literature searches were completed using the following databases: PubMed, Cumulative Index to Nursing and Allied Health Literature, and PsychInfo. The key words: cancer or advanced cancer or neoplasm, AND palliative care or terminal care or hospice or end-of-life, AND symptoms or multiple symptoms or symptom clusters were combined. RESULTS: Twenty-two studies met the inclusion criteria and examined at least one of our purposes. The majority of these studies were descriptive and used one of four common symptom assessment scales. Fifty-six different signs and symptoms were evaluated across various dimensions (i.e., prevalence, severity, distress, frequency, control). Pain, dyspnea, and nausea were the only symptoms measured in all 22 studies. Relationships among concurrent symptoms were examined in nine studies. Relationships among symptoms and predictors (i.e., demographics, cancer type, healthcare delivery environment) were examined in seven studies. Relationships among symptoms and outcomes (i.e., functional status, psychological status, quality-of-life, survival time) were examined in 14 studies. Significant methodological variation was found among these studies. SIGNIFICANCE OF RESULTS: It is difficult to draw conclusions about the relationships among multiple symptoms, predictors, and outcomes due to the heterogeneity of these studies. Future research is needed to determine which symptoms and symptom dimensions to assess in order to better understand how multiple symptoms relate to each other as well to as predictors and outcomes in palliative care patients with advanced cancer.

STUDY OBJECTIVES: To examine how self-reported ratings of sleep disturbance changed from the time of the simulation visit to four months after the completion of radiation therapy (RT) and to investigate whether specific patient, disease, and symptom characteristics predicted the initial levels of sleep disturbance and/or characteristics of the trajectories of sleep disturbance. DESIGN: Prospective longitudinal study. SETTING: Two radiation therapy centers. PATIENTS: Patients (n = 82) who underwent primary or adjuvant RT for prostate cancer. MEASUREMENTS AND RESULTS: Changes in self-reported sleep disturbance were measured using the General Sleep Disturbance Scale (GSDS). Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression Scale. Trait and state anxiety were measured using the Spielberger State-Trait Anxiety Inventory. Hierarchical linear modeling was used to answer the study aims. Self-reported sleep disturbance increased during the course of RT and then decreased following the completion of RT. Predictors of higher levels of sleep disturbance included younger age, higher levels of trait anxiety, higher levels of depressive symptoms, and higher levels of sleep disturbance at the initiation of RT. CONCLUSIONS: Sleep disturbance is a significant problem in patients with prostate cancer who undergo RT. Younger men with co-occurring depression and anxiety may be at greatest risk for sleep disturbance during RT.

AIM: Endothelial lipase (EL) is a key enzyme in lipid metabolism, and a polymorphism in the EL gene may be a candidate for modulating lipid parameters in type 2 diabetic (T2D) patients. METHODS: In 396 T2D patients (age: 59.5 +/- 10.7 years; BMI: 28.9 +/- 5.3 kg/m(2); HbA(1c): 8.2 +/- 1.9%), the c.584C>T polymorphism (rs2000813, p.Thr111Ile) was studied in 225 men (frequency of c.584T: 0.351) and 171 women (frequency of c.584T: 0.304). Patients' metabolic parameters, and macrovascular and microvascular complications, were assessed at baseline and at follow-up (mean: 4.2 years). RESULTS: Patients who were homozygous for the minor allele displayed modestly decreased low-density lipoprotein (LDL) cholesterol and raised apolipoprotein B at baseline, and raised systolic blood pressure and high-density lipoprotein (HDL) cholesterol on follow-up. Homozygosity for the minor allele was significantly associated with frequency of retinopathy (P=0.025), with TT homozygous patients more likely to have diabetic retinopathy (OR: 3.505; 95% CI: 1.491-8.239) both initially and at follow-up. CONCLUSION: The c.584C>T EL polymorphism is associated with a higher risk of diabetic retinopathy that could be linked to modifications in HDL-cholesterol metabolism and blood pressure levels.

Multiple concurrent symptoms are highly prevalent in patients with cancer. However, little is known about the relationships among these symptoms and their underlying mechanisms. A number of cytokines that are involved in the development of sickness behavior are hypothesized to be a mechanism for symptom clusters. Measurement of these cytokines would provide valuable information that could be used to elucidate mechanisms underlying the development of symptom clusters and the identification of potential targets for intervention studies. In this article, the authors explore several issues that warrant careful consideration when designing a research study involving the use of a cytokine as a biomarker in symptom cluster research. These issues include which molecules to measure, which specimens to collect, the timing of specimen collection and processing, and which technologies to use to measure the biomarker and the sensitivity and specificity of the assay system. The article begins with a brief discussion of cytokines and sickness behavior and the role of the cytokines in cancer-related symptoms.

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.

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.

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 (>90 cm for men; >80 cm, women), triglycerides (>150 mg/dL), high-density lipoprotein cholesterol (HDL-C) (<40 mg/dL (men), < mg/dL (women)), blood pressure (>135/80 mmHg), and fasting glucose (>100 mg/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.