Faculty Bibliography

CONTEXT: Little is known about the occurrence and severity of sleep disturbance and fatigue between patients with common cancer diagnoses. OBJECTIVES: Study purposes were to evaluate for differences in the occurrence rates of sleep disturbances and fatigue; evaluate for differences in the severity of sleep disturbance using both subjective and objective measures; and evaluate for differences in the severity of self-reported fatigue in patients with breast and prostate cancer at the initiation of radiation therapy (RT). METHODS: Patients with breast (n=78) and prostate (n=82) cancer were evaluated before the initiation of RT using the Pittsburgh Sleep Quality Index, General Sleep Disturbance Scale, Lee Fatigue Scale, and wrist actigraphy. Differences in sleep disturbance and fatigue between groups were evaluated using independent sample t-tests and Chi-square analyses. RESULTS: Occurrence rates for sleep disturbance (P<0.0001) and fatigue (P=0.03) were significantly higher in patients with breast compared with prostate cancer. Patients with breast cancer self-reported significantly higher levels of sleep disturbance (P=0.008) and fatigue (P=0.005) than patients with prostate cancer. However, using actigraphy, patients with prostate cancer had poorer sleep efficiency (P=0.02) than patients with breast cancer. CONCLUSION: Based on self-report, patients with breast cancer experience sleep disturbance more frequently and with greater severity than patients with prostate cancer. Objective measures of sleep disturbance suggest that prostate cancer patients have more severe sleep disturbance than breast cancer patients. All the patients experienced poor sleep quality and fatigue, which suggests that oncology patients need to be assessed for these symptoms.

BACKGROUND: Epidemiologic evidence suggests a heritable component to risk for sudden cardiac arrest independent of risk for myocardial infarction. Recent candidate gene association studies for community sudden cardiac arrests have focused on a limited number of biological pathways and yielded conflicting results. We sought to identify novel gene associations for sudden cardiac arrest in patients with coronary artery disease by performing a genome-wide association study. METHODS: Tagging SNPs (n = 338,328) spanning the genome were typed in a case-control study comparing 89 patients with coronary artery disease and sudden cardiac arrest due to ventricular tachycardia or ventricular fibrillation to 520 healthy controls. RESULTS: Fourteen SNPs including 7 SNPs among 7 genes (ACYP2, AP1G2, ESR1, DGES2, GRIA1, KCTD1, ZNF385B) were associated with sudden cardiac arrest (all p < 1.30 x 10(-7)), following Bonferroni correction and adjustment for population substructure, age, and sex; genetic variation in ESR1 (p = 2.62 x 10(-8); Odds Ratio [OR] = 1.43, 95% confidence interval [CI]:1.277, 1.596) has previously been established as a risk factor for cardiovascular disease. In tandem, the role of 9 genes for monogenic long QT syndrome (LQT1-9) was assessed, yielding evidence of association with CACNA1C (LQT8; p = 3.09 x 10(-4); OR = 1.18, 95% CI:1.079, 1.290). We also assessed 4 recently published gene associations for sudden cardiac arrest, validating NOS1AP (p = 4.50 x 10(-2), OR = 1.15, 95% CI:1.003, 1.326), CSMD2 (p = 6.6 x 10(-3), OR = 2.27, 95% CI:1.681, 2.859), and AGTR1 (p = 3.00 x 10(-3), OR = 1.13, 95% CI:1.042, 1.215). CONCLUSION: We demonstrate 11 gene associations for sudden cardiac arrest due to ventricular tachycardia/ventricular fibrillation in patients with coronary artery disease. Validation studies in independent cohorts and functional studies are required to confirm these associations.

BACKGROUND: Little is known about the relationships between sleep parameters and fatigue in patients at the initiation of radiation therapy (RT). OBJECTIVES: The objectives of this study were to describe values for nocturnal sleep/rest, daytime wake/activity, and circadian activity rhythm parameters measured using actigraphy and to evaluate the relationships between these objective parameters and subjective ratings of sleep disturbance and fatigue severity, in a sample of patients at the initiation of RT. METHODS: Patients (n = 185) with breast, prostate, lung, or brain cancer completed self-report measures for sleep disturbance (ie, Pittsburgh Sleep Quality Index, General Sleep Disturbance Scale) and fatigue (Lee Fatigue Scale) and wore wrist actigraphs for a total of 48 hours prior to beginning RT. Actigraphy data were analyzed using the Cole-Kripke algorithm. Spearman rank correlations were calculated between variables. RESULTS: Approximately 30% to 50% of patients experienced sleep disturbance, depending on whether clinically significant cutoffs for the subjective or objective measures were used to calculate occurrence rates. In addition, these patients reported moderate levels of fatigue. Only a limited number of significant correlations were found between the subjective and objective measures of sleep disturbance. Significant positive correlations were found between the subjective, but not the objective measures of sleep disturbance and fatigue. CONCLUSIONS: A significant percentage of oncology patients experience significant disturbances in sleep-wake circadian activity rhythms at the initiation of RT. The disturbances occur in both sleep initiation and sleep maintenance. IMPLICATIONS FOR PRACTICE: Patients need to be assessed at the initiation of RT for sleep disturbance, so appropriate treatment is initiated.

Symptom burden has been identified as a predictor of medication adherence, but little is known about which symptoms are most strongly implicated. This study examines self-reported medical adherence in relation to demographic, clinical, and symptom characteristics among 302 adults living with HIV. Only 12% reported missing medication during the 3-day assessment, but 75% gave at least one reason for missing it in the previous month. Poor adherence was associated with higher viral load and greater symptom burden. Trouble sleeping and difficulty concentrating were strongly associated with poor adherence. Given that "forgetting" was the most common reason for missing medication and nearly one third reported sleeping through dose time, future research should examine the influence of sleep disturbance on adherence. Effective management of common symptoms, such as sleep disturbance, fatigue, and gastrointestinal side-effects of medications may result in better adherence, as well as improved clinical outcomes and quality of life.

Our knowledge of pharmacogenetic variability in diverse populations is scarce, especially in sub-Saharan Africa. To bridge this gap in knowledge, we characterised population frequencies of clinically relevant pharmacogenetic traits in two distinct South African population groups. We genotyped 211 tagging single nucleotide polymorphisms (tagSNPs) in 12 genes that influence antiretroviral drug disposition, in 176 South African individuals belonging to two distinct population groups residing in the Western Cape: the Xhosa (n = 109) and Cape Mixed Ancestry (CMA) (n = 67) groups. The minor allele frequencies (MAFs) of eight tagSNPs in six genes (those encoding the ATP binding cassette sub-family B, member 1 [ABCB1], four members of the cytochrome P450 family [CYP2A7P1, CYP2C18, CYP3A4, CYP3A5] and UDP-glucuronosyltransferase 1 [UGT1A1]) were significantly different between the Xhosa and CMA populations (Bonferroni p < 0.05). Twenty-seven haplotypes were inferred in four genes (CYP2C18, CYP3A4, the gene encoding solute carrier family 22 member 6 [SLC22A6] and UGT1A1) between the two South African populations. Characterising the Xhosa and CMA population frequencies of variant alleles important for drug transport and metabolism can help to establish the clinical relevance of pharmacogenetic testing in these populations.

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.