Faculty Bibliography

CONTEXT: Sleep disturbance is a significant problem in oncology patients. OBJECTIVES: To examine how actigraphy and self-report ratings of sleep disturbance changed over the course of and after radiation therapy (RT); investigate whether specific patient, disease, and symptom characteristics predicted the initial levels and/or the characteristics of the trajectories of sleep disturbance; and compare predictors of subjective and objective sleep disturbance. METHODS: Patients (n=73) completed self-report questionnaires that assessed sleep disturbance, fatigue, depressive symptoms, anxiety, and pain before the initiation of RT through four months after the completion of RT. Wrist actigraphy was used as the objective measure of sleep disturbance. Hierarchical linear modeling was used for data analyses. RESULTS: Mean wake after sleep onset was 11.9% and mean total score on the General Sleep Disturbance Scale was 45. More than 85% of the patients had an abnormally high number of nighttime awakenings. Substantial interindividual variability was found for both objective and subjective measures of sleep disturbance. Body mass index predicted baseline levels of objective sleep disturbance. Comorbidity, evening fatigue, and depressive symptoms predicted baseline levels of subjective sleep disturbance, and depressive symptoms predicted the trajectory of subjective sleep disturbance. CONCLUSION: Different variables predicted sleep disturbance using subjective and objective measures. The slightly elevated wake after sleep onset found may be an underestimation of the degree of sleep disturbance when it is evaluated in the context of the high number of nighttime awakenings and patient's perception of poor sleep quality and quantity.

BACKGROUND: Clinicians use CA125, a tumor-associated antigen, primarily to monitor epithelial ovarian cancer. However, CA125 lacks the sensitivity and specificity necessary for population-based screening in healthy women. The purpose of this study was to determine if serum concentrations of CA125 differed across the three phases of the menstrual cycle in healthy, premenopausal women using two commercially available assays. METHODS: Healthy, Caucasian women between the ages of 18 and 39 were enrolled using strict criteria to exclude factors known to contribute to CA125 fluctuations. Menstrual cycle regularity was determined using calendars maintained by participants for 3 months. After cycle regularity was established, blood was drawn at three time points for CA125 determination using two commercial assays (i.e., Siemens and Panomics). RESULTS: Regardless of the assay used, CA125 values were highest during menses. The CA125 values decreased 0.2 U/ml per day from menses to the end of the same cycle, which resulted in a net decrease of 5.8 U/ml across the cycle. CONCLUSIONS: The two commercial assays for CA125 determination demonstrated good concordance in terms of reference ranges regardless of epitope differences. While CA125 levels changed over the course of the menstrual cycle, these changes may not be clinically significant in healthy women. This study is the first to control for factors known to contribute to CA125 elevations; to quantify a decrease in CA125 levels across the menstrual cycle; and to confirm concordance in the relative decreases in serum CA125 levels across the menstrual cycle between two frequently used commercial assays.

Because multiple symptoms associated with "sickness behavior" have a negative impact on functional status and quality of life, increased information on the mechanisms that underlie inter-individual variability in this symptom experience is needed. The purposes of this study were to determine: if distinct classes of individuals could be identified based on their experience with pain, fatigue, sleep disturbance, and depression; if these classes differed on demographic and clinical characteristics; and if variations in pro- and anti- inflammatory cytokine genes were associated with latent class membership. Self-report measures of pain, fatigue, sleep disturbance, and depression were completed by 168 oncology outpatients and 85 family caregivers (FCs). Using latent class profile analysis (LCPA), three relatively distinct classes were identified: those who reported low depression and low pain (83%), those who reported high depression and low pain (4.7%), and those who reported high levels of all four symptoms (12.3%). The minor allele of IL4 rs2243248 was associated with membership in the "All high" class along with younger age, being White, being a patient (versus a FC), having a lower functional status score, and having a higher number of comorbid conditions. Findings suggest that LPCA can be used to differentiate distinct phenotypes based on a symptom cluster associated with sickness behavior. Identification of distinct phenotypes provides new evidence for the role of IL4 in the modulation of a sickness behavior symptom cluster in oncology patients and their FCs.

The purposes of this study were to determine the occurrence rate for preoperative breast pain; describe the characteristics of this pain; evaluate for differences in demographic and clinical characteristics; and evaluate for variations in pro- and anti-inflammatory cytokine genes between women who did and did not report pain. Patients (n = 398) were recruited prior to surgery and completed self-report questionnaires on a number of pain characteristics. Genotyping was done using a custom genotyping array. Women (28.2%) who reported breast pain were significantly younger (P < .001); more likely to be nonwhite (P = .032); reported significantly lower Karnofsky Performance Status scores (P = .008); were less likely to be postmenopausal (P = .012); and had undergone significantly more biopsies (P = .006). Carriers of the minor allele for a single nucleotide polymorphism in interleukin (IL)1-receptor 1 (IL1R1) (rs2110726) were less likely to report breast pain prior to surgery (P = .007). Carriers of the minor allele for a single nucleotide polymorphism in IL13 (rs1295686) were more likely to report breast pain prior to surgery (P = .019). Findings suggest that breast pain occurs in over a quarter of women who are about to undergo breast cancer surgery. Based on phenotypic and genotypic characteristics found, inflammatory mechanisms contribute to preoperative breast pain. PERSPECTIVE: In women with breast cancer, preoperative pain may be associated with increases in inflammatory responses associated with an increased number of biopsies. In addition, differences in cytokine genes may contribute to this preoperative breast pain.

OBJECTIVES: To review the evidence on a number of biomarkers that show potential clinical utility in the prediction of and treatment responsiveness for the four most common symptoms associated with cancer and its treatment (ie, pain, fatigue, sleep disturbance, depression). DATA SOURCES: Review and synthesis of review articles and data-based publications. CONCLUSION: A growing body of evidence suggests that sensitive and specific biomarkers will be available to assist clinicians with the assessment and management of symptoms. IMPLICATIONS FOR NURSING PRACTICE: Nurses will play a critical role in educating patients about their risk for specific symptoms based on an evaluation of specific biomarkers. Nurses will be involved in using biomarker data to titrate medications based on patient's responses to symptom management interventions.

OBJECTIVE: To characterize specific types of sleep problems experienced by adults with HIV. METHOD: The design was cross-sectional involving sleep questionnaires, diaries, and wrist actigraphy. The convenience sample included 290 adults living with HIV, 22-77 years of age. Measures included self-report for sleep onset latency, and wrist actigraphy estimates of total sleep time at night, wake after sleep onset, and daytime sleep. RESULTS: Nearly half (45%) of the sample slept < 6 h per night. Difficulty falling asleep was reported by 34%, and 56% had fragmented sleep according to actigraphy; 20% had both problems, and 30% were good sleepers. Participants reporting difficulty falling asleep had actigraphy and clinical measures similar to the good sleepers, but subjectively they experienced greater sleep disturbance and symptom burden (particularly anxiety and morning fatigue) and reported more use of sleep medication. Participants with fragmented sleep reported low levels of sleep disturbance and symptom burden similar to the good sleepers, despite actigraphy measures indicating they obtained less sleep both at night and during the day. Sleep fragmentation was also associated with sociodemographic factors and slightly lower CD4+ T-cell counts. Participants reporting both sleep problems had actigraphy and clinical profiles similar to those who had only fragmented sleep, but their symptom experience was similar to participants with only sleep initiation difficulties. CONCLUSIONS: Findings support the need for targeting efforts to improve sleep for the majority of adults living with HIV/AIDS and tailoring interventions to the specific type of sleep problem regardless of the person's clinical and demographic profile.

PURPOSE: Anxiety is common in patients undergoing radiation therapy (RT) and in their family caregivers (FCs). Little is known about individual differences in anxiety trajectories during and after RT. This study aimed to identify distinct latent classes of oncology patients and their FCs based on self-reported anxiety symptoms from the beginning to four months after the completion of RT. METHOD: Using growth mixture modeling (GMM), longitudinal changes in Spielberger State Anxiety Inventory (STAI-S) scores among 167 oncology outpatients with breast, prostate, lung, or brain cancer and 85 FCs were evaluated to determine distinct anxiety symptom profiles. STAI-S scores were assessed just prior to, throughout the course of, and for four months following RT (total of 7 assessments). Baseline trait anxiety and depressive symptoms (during and after RT) were also assessed. RESULTS: The GMM analysis identified three latent classes of oncology patients and FCs with distinct trajectories of state anxiety: Low Stable (n = 93, 36.9%), Intermediate Decelerating (n = 82, 32.5%), and High (n = 77, 30.6%) classes. Younger participants, women, ethnic minorities, and those with children at home were more likely to be classified in the High anxiety class. Higher levels of trait anxiety and depressive symptoms, at the initiation of RT, were associated with being in the High anxiety class. CONCLUSIONS: Subgroups of patients and FCs with high, intermediate, and low mean levels of anxiety during and after RT were identified with GMM. Additional research is needed to better understand the heterogeneity of symptom experiences as well as comorbid symptoms in patients and FCs.

Hereditary haemorrhagic telangiectasia (HHT) [corrected] is a vascular dysplasia syndrome caused by mutations in transforming growth factor-beta/bone morphogenetic protein pathway genes, ENG and ACVRL1. HHT [corrected] shows considerable variation in clinical manifestations, suggesting environmental and/or genetic modifier effects. Strain-specific penetrance of the vascular phenotypes of Eng(+/-) and Tgfb1(-/-) mice provides further support for genetic modification of transforming growth factor-beta pathway deficits. We previously identified variant genomic loci, including Tgfbm2, which suppress prenatal vascular lethality of Tgfb1(-/-) mice. Here we show that human polymorphic variants of PTPN14 within the orthologous TGFBM2 locus influence clinical severity of HHT, [corrected] as assessed by development of pulmonary arteriovenous malformation. We also show that PTPN14, ACVRL1 and EFNB2, encoding EphrinB2, show interdependent expression in primary arterial endothelial cells in vitro. This suggests an involvement of PTPN14 in angiogenesis and/or arteriovenous fate, acting via EphrinB2 and ACVRL1/activin receptor-like kinase 1. These findings contribute to a deeper understanding of the molecular pathology of HHT [corrected] in particular and to angiogenesis in general.