Faculty Bibliography

OBJECTIVES: This study assessed the prevalence of insomnia symptoms among women with and without HIV-infection and examined factors associated with insomnia. DESIGN: Participants (n = 1682) were enrolled in the Women's Interagency HIV Study (WIHS); 69% were infected with HIV. This was a cross-sectional analysis of data from standardized interviewer-administered instruments and physical/gynecological exams. Analysis focused on sociodemographics, sleep measures, depressive symptoms, drug use, alcohol consumption, medications, and HIV-related clinical variables. Women were classified as having symptoms of insomnia if they reported either difficulty initiating sleep, difficulty maintaining sleep, or early morning awakening >/= 3 times a week in the past 2 weeks. RESULTS: Overall, HIV-infected women were 17% more likely to endorse insomnia symptoms than uninfected women (OR = 1.17, 95% CI: 1.04-1.34, P < 0.05). The adjusted prevalence of insomnia symptoms varied by HIV status and age groups. Among women ages 31-40 years, those with HIV infection were 26% more likely to endorse insomnia symptoms than their counterparts (OR = 1.26, 95% CI: 1.01-1.59, P < 0.05). No significant differences were observed in the likelihood of reporting insomnia symptoms based on HIV treatment type. Multivariate-adjusted regression analyses showed that depression was the most consistent and significant independent predictor of the likelihood of reporting insomnia symptoms across all age strata. CONCLUSIONS: Insomnia symptoms are common among both HIV-infected and uninfected women. Prevalence of insomnia did not vary significantly by HIV status, except among younger women. Younger women with HIV infection are at greater risk for experiencing insomnia symptoms.

BACKGROUND: Little is known about the relationships between sleep/wake circadian activity rhythms and fatigue in family caregivers (FCs) of oncology patients. 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 subjective and objective measures of sleep disturbance and self-reported fatigue severity, in a sample of FCs of oncology patients. METHODS: Family caregivers (n = 103) 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 48 hours prior to beginning radiation therapy. Spearman rank correlations were calculated between variables. RESULTS: Approximately 40% to 60% of FCs experienced sleep disturbance depending on whether clinically significant cutoffs for the subjective or objective measures were used to calculate occurrence rates. In addition, these FCs 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 fatigue and subjective, but not objective measures of sleep disturbance. The amplitude of circadian activity rhythm was not related to any objective sleep measure but was correlated with self-report of longer sleep-onset latency. CONCLUSIONS: A significant percentage of FCs experience clinically meaningful disturbances in sleep-wake circadian activity rhythms. These disturbances occur primarily in sleep maintenance. IMPLICATIONS FOR PRACTICE: Family caregivers need to be assessed, along with patients, for sleep disturbance, and appropriate interventions initiated for them and for the patient.

Vitamin E was recently shown to improve hepatic histology in a randomized controlled trial of pioglitazone or vitamin E for nonalcoholic steatohepatitis (PIVENS). The current study utilized samples collected in the PIVENS trial to identify: (1) baseline metabolomic profiles that could identify who would respond to vitamin E treatment and (2) end of treatment metabolomic profiles reflective of histologic improvement. A comprehensive analysis of metabolomics profiles (n = 547) quantified by mass spectrometry was performed in vitamin E responders (n = 16), vitamin E non-responders (n = 15), and placebo responders (n = 15). At baseline, phenyl-propionic acid (Odds ratio: 29.4, p<0.01), indole-propionic acid levels (Odds ratio: 16.2, p<0.01) were directly associated with a subsequent histologic response to vitamin E treatment whereas gamma-carboxyethylhydroxychroman (CEHC) levels were inversely related to histologic response. Adjusting for baseline values by analysis of covariance, the end of treatment levels of gamma-glutamyl leucine (Fold change: 0.82, p<0.02) and gamma-glutamyl valine (Fold change: 0.8, p<0.03) were significantly lower in vitamin E responders compared to non-responders. The levels of gamma-glutamyl transpeptidase were not significantly different across the two groups. Subjects receiving placebo who demonstrated a histologic improvement also demonstrated lower levels of gamma-glutamylated amino acids (leucine, valine and isoleucine) compared to vitamin E non-responders. These data provide exploratory proof that there are measurable differences in the metabolic profile of subjects who are likely (vs unlikely) to respond to vitamin E treatment for NASH and in those experiencing histologic improvement (vs no improvement) on treatment and support further studies to validate these biomarkers.

The purposes of this study were to identify distinct latent classes of individuals based on subjective reports of sleep disturbance; to examine differences in demographic, clinical, and symptom characteristics between the latent classes; and to evaluate for variations in pro- and anti-inflammatory cytokine genes between the latent classes. 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 General Sleep Disturbance Scale (GSDS) obtained prior to, during, and for four months following completion of radiation therapy. Single nucleotide polymorphisms (SNPs) and haplotypes in candidate cytokine genes were interrogated for differences between the two latent classes. Multiple logistic regression was used to assess the effect of phenotypic and genotypic characteristics on GSDS group membership. Two latent classes were identified: lower sleep disturbance (88.5%) and higher sleep disturbance (11.5%). Participants who were younger and had a lower Karnofsky Performance status score were more likely to be in the higher sleep disturbance class. Variation in two cytokine genes (i.e., IL6, NFKB) predicted latent class membership. Evidence was found for latent classes with distinct sleep disturbance trajectories. Unique genetic markers in cytokine genes may partially explain the interindividual heterogeneity characterizing these trajectories.

OBJECTIVE: Depressive symptoms, common in breast cancer patients, may increase, decrease, or remain stable over the course of treatment. Most longitudinal studies have reported mean symptom scores that tend to obscure interindividual heterogeneity in the symptom experience. The identification of different trajectories of depressive symptoms may help identify patients who require an intervention. This study aimed to identify distinct subgroups of breast cancer patients with different trajectories of depressive symptoms in the first six months after surgery. METHOD: Among 398 patients with breast cancer, growth mixture modeling was used to identify latent classes of patients with distinct depressive symptom profiles. These profiles were identified based on Center for Epidemiological Studies-Depression (CES-D) scale scores completed just prior to surgery, and 1, 2, 3, 4, 5, and 6 months after surgery. RESULTS: Four latent classes of breast cancer patients with distinct depressive symptom trajectories were identified: Low Decelerating (38.9%), Intermediate (45.2%), Late Accelerating (11.3%), and Parabolic (4.5%) classes. Patients in the Intermediate class were younger, on average, than those in the Low Decelerating class. The Intermediate, Late Accelerating, and Parabolic classes had higher mean baseline anxiety scores compared to the Low Decelerating class. CONCLUSIONS: Breast cancer patients experience different trajectories of depressive symptoms after surgery. Of note, over 60% of these women were classified into one of three distinct subgroups with clinically significant levels of depressive symptoms. Identification of phenotypic and genotypic predictors of these depressive symptom trajectories after cancer treatment warrants additional investigation.

PURPOSE: To examine the psychometric properties of the 9-item Fatigue Severity Scale (FSS) using a Rasch model application. METHODS: A convenience sample of HIV-infected adults was recruited, and a subset of the sample was assessed at 6-month intervals for 2 years. Socio-demographic, clinical, and symptom data were collected by self-report questionnaires. CD4 T-cell count and viral load measures were obtained from medical records. The Rasch analysis included 316 participants with 698 valid questionnaires. RESULTS: FSS item 2 did not advanced monotonically, and items 1 and 2 did not show acceptable goodness-of-fit to the Rasch model. A reduced FSS 7-item version demonstrated acceptable goodness-of-fit and explained 61.2% of the total variance in the scale. In the FSS-7 item version, no uniform Differential Item Functioning was found in relation to time of evaluation or to any of the socio-demographic or clinical variables. CONCLUSION: This study demonstrated that the FSS-7 has better psychometric properties than the FSS-9 in this HIV sample and that responses to the different items are comparable over time and unrelated to socio-demographic and clinical variables.

Acetylation is increasingly recognized as an important metabolic regulatory posttranslational protein modification, yet the metabolic consequence of mitochondrial protein hyperacetylation is unknown. We find that high-fat diet (HFD) feeding induces hepatic mitochondrial protein hyperacetylation in mice and downregulation of the major mitochondrial protein deacetylase SIRT3. Mice lacking SIRT3 (SIRT3KO) placed on a HFD show accelerated obesity, insulin resistance, hyperlipidemia, and steatohepatitis compared to wild-type (WT) mice. The lipogenic enzyme stearoyl-CoA desaturase 1 is highly induced in SIRT3KO mice, and its deletion rescues both WT and SIRT3KO mice from HFD-induced hepatic steatosis and insulin resistance. We further identify a single nucleotide polymorphism in the human SIRT3 gene that is suggestive of a genetic association with the metabolic syndrome. This polymorphism encodes a point mutation in the SIRT3 protein, which reduces its overall enzymatic efficiency. Our findings show that loss of SIRT3 and dysregulation of mitochondrial protein acetylation contribute to the metabolic syndrome.

BACKGROUND: Attentional fatigue is experienced as a decreased ability to concentrate, engage in purposeful activity, and maintain social relationships when there are competing demands on attention. Breast and prostate cancer are the 2 most common cancers in women and men, respectively. Most previous studies on self-reported attentional fatigue evaluated patients with breast cancer. OBJECTIVES: The objectives of the study were to determine if self-reported attentional fatigue differed in patients with breast cancer and prostate cancer before radiation therapy (RT) and to determine the relationships between attentional fatigue and other symptoms in these 2 groups. METHODS: Patients (n = 155) completed questionnaires before RT. Descriptive statistics, Pearson correlations, and analysis of covariance were used for data analyses. RESULTS: After controlling for age, patients with breast cancer reported significantly higher levels of attentional fatigue. In both groups, more attentional fatigue correlated significantly with more anxiety, depression, sleep disturbance, and physical fatigue. These correlations were stronger for patients with breast cancer. CONCLUSIONS: The present study is the first to identify differences in self-reported attentional fatigue between these 2 groups before RT. Additional research is warranted to determine factors that contribute to these differences, as well as mechanisms that underlie the development of attentional fatigue. IMPLICATIONS FOR PRACTICE: Clinicians should consider the capacity of their patients to direct attention when learning about RT and other treatments. It is important to simplify confusing healthcare terminology and reinforce teaching that is most important both verbally and in writing. Appropriate interventions for anxiety and depression may decrease attentional fatigue in these patients.

AIMS AND OBJECTIVES: Describe patterns of morning and evening fatigue in adults with HIV and examine their relationship to demographic and clinical factors and other symptoms. BACKGROUND: Most studies of HIV-related fatigue assess average levels of fatigue and do not address its diurnal fluctuations. Patterns of fatigue over the course of the day may have important implications for assessment and treatment. DESIGN: A cross-sectional, correlational design was used with six repeated measures over 72 hours. METHOD: A convenience sample of 318 HIV-infected adults was recruited in San Francisco. Socio-demographic, clinical and symptom data were collected with questionnaires. CD4+ T-cell count and viral load were obtained from medical records. Participants completed a four-item version of the Lee Fatigue Scale each morning and evening for three consecutive days. Participants were grouped based on their diurnal pattern of fatigue (high evening only, high morning only, high morning and evening and low morning and evening). Group comparisons and logistic regression were used to determine the unique predictors of each fatigue pattern. RESULTS: The high evening fatigue pattern was associated with anxiety and the high morning pattern was associated with anxiety and depression. The morning fatigue pattern showed very little fluctuation between morning and evening, the evening pattern showed the largest fluctuation. The high morning and evening pattern was associated with anxiety, depression and sleep disturbance and this group reported the most fatigue-related distress and interference in functioning. CONCLUSIONS: These results provide initial evidence for the importance of assessing the patient's daily pattern of fatigue fluctuation, as different patterns were associated with different symptom experiences and perhaps different aetiologies. RELEVANCE TO CLINICAL PRACTICE: Different fatigue patterns may benefit from tailored intervention strategies. Management of depressive symptoms could be tested in patients who experience high levels of morning fatigue.