Bradley E. Aouizerat

Abstract

Context. Radiation therapy (RT) is a common treatment for prostate cancer. Despite available research, prostate cancer patients report that information about side effects is their most important unmet need. Additional research is needed that focuses on specific dimensions of the patient's symptom experience. Objectives. The study's purposes were to evaluate the trajectories of occurrence, severity, and distress of the six most prevalent symptoms reported by patients undergoing RT for prostate cancer and the effects of selected demographic and clinical characteristics on these trajectories. Methods. Patients completed the Memorial Symptom Assessment Scale 11 times before, during, and after RT. For problems with urination, pain, lack of energy, feeling drowsy, difficulty sleeping, and diarrhea, the trajectories of occurrence, severity, and distress were evaluated using multilevel generalized linear models. Results. Across all three dimensions, pain, lack of energy, feeling drowsy, and difficulty sleeping followed a decreasing linear trend. Problems with urination and diarrhea demonstrated more complex patterns of change over time. Conclusion. Although longitudinal data on pain, lack of energy, feeling drowsy, and difficulty sleeping are limited, they are highly prevalent symptoms in these patients. In addition, diarrhea becomes a significant problem for these patients over the course of RT. A number of demographic and clinical characteristics affect the trajectories of these common symptoms differentially.

Abstract

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.

Abstract

OBJECTIVE: CYP2B6 variation predicts pharmacokinetic characteristics of its substrates. Consideration for underlying genetic structure is critical to protect against spurious associations with the highly polymorphic CYP2B6 gene. DESIGN: The effect of CYP2B6 variation on response to its substrates, nonnucleoside reverse transcriptase inhibitors (NNRTIs), was explored in the Women's Interagency HIV Study. METHODS: Five putative functional polymorphisms were tested for associations with virologic suppression within 1 year after NNRTI initiation in women naive to antiretroviral agents (n=91). Principal components were generated to control for population substructure. Logistic regression was used to test the joint effect of rs3745274 and rs28399499, which together indicate slow, intermediate, and extensive metabolizers. RESULTS: Rs3745274 was significantly associated with virologic suppression [odds ratio=3.61, 95% confidence interval (CI) 1.16-11.22, P trend=0.03]; the remaining polymorphisms tested were not significantly associated with response. Women classified as intermediate and slow metabolizers were 2.90 (95% CI 0.79-12.28) and 13.44 (95% CI 1.66 to infinity) times as likely to achieve virologic suppression compared to extensive metabolizers after adjustment for principal components (P trend=0.005). Failure to control for genetic ancestry resulted in substantial confounding of the relationship between the metabolizer phenotype and treatment response. CONCLUSION: The CYP2B6 metabolizer phenotype was significantly associated with virologic response to NNRTIs; this relationship would have been masked by simple adjustment for self-reported ethnicity. Given the appreciable genetic heterogeneity that exists within self-reported ethnicity, these results exemplify the importance of characterizing underlying genetic structure in pharmacogenetic studies. Further follow-up of the CYP2B6 metabolizer phenotype is warranted, given the potential clinical importance of this finding.

Abstract

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.

Abstract

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). Twentyseven 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.

Abstract

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±5.3kg/m2; HbA1c: 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.

Abstract

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.

Abstract

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.

Abstract

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.