Publications

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Objective: Dopamine, iron, and inflammatory pathways are considered important to the development of restless legs syndrome (RLS). Recent genetic studies support involvement of dopamine and iron; however, cytokine gene variation in the inflammatory component remains unexplored. A recent study reported a high prevalence of RLS among HIV-infected adults. We estimate occurrence of RLS in an ethnically diverse sample of HIV-infected adults and examine differences in demographic factors, clinical characteristics, and biomarkers relating to dopamine, iron, and inflammation between adults with and without RLS symptoms. Design: A prospective longitudinal study aimed at identifying biomarkers of RLS symptom experience among HIV-infected adults. Method: 316 HIV-positive adults were evaluated using International RLS Study Group criteria. Genes were chosen for hypothesized relationships to dopamine (NOS1, NOS2), iron (HFE) or inflammation-mediated by cytokine genes (interferon [IFN], interleukin [IL], nuclear factor kappa-B [NFKB], and tumor necrosis factor alpha [TNFA]). Results: Similar to general population estimates, 11% of the sample met all four RLS diagnostic criteria. Controlling for race, gender, and hemoglobin, carrying two copies of the minor allele for IL1B rs1143643, rs1143634, or rs1143633 or carrying the minor allele for IL17A rs8193036 was associated with increased likelihood of meeting RLS diagnostic criteria. Conclusion: This study provides preliminary evidence of a genetic association between IL1B and IL17A genes and RLS.

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Objective The purpose of this study was to examine the relationship between second-trimester maternal serum biomarkers and the development of early- and late-onset severe preeclampsia in euploid pregnancies. Study Design Included were 136,139 pregnancies that obtained second-trimester prenatal screening through the California Prenatal Screening Program with live births in 2006-2008. We identified severe preeclampsia diagnoses from hospital discharge records. We used log binomial regression to examine the association between abnormal second-trimester maternal serum biomarkers and the development of severe preeclampsia.Results Approximately 0.9% of all women (n = 1208) in our sample experienced severe preeclampsia; 329 women at <34 weeks' gestation and 879 women ≥34 weeks' gestation. High levels of alpha fetoprotein (AFP), human chorionic gonadotropin, inhibin (multiple of the median, ≥95th percentile), and low unconjugated estriol (multiple of the median, ≤5th percentile), were associated with severe preeclampsia (relative risk, 2.5-11.7). Biomarkers were more predictive of early-onset severe preeclampsia (relative risk, 3.8-11.7). One in 9.5 pregnancies with combined high AFP, inhibin, and low unconjugated estriol levels experienced severe early-onset preeclampsia compared with 1 in 680.5 pregnancies without any abnormal biomarkers.Conclusion The risk of the development of severe preeclampsia increases for women with high second-trimester AFP, human chorionic gonadotropin, inhibin, and/or low unconjugated estriol; this is especially true for early-onset severe preeclampsia. When abnormal biomarkers co-occur, risk dramatically increases. Although the screening value of second-trimester biomarkers is low, abnormal biomarkers, especially when occurring in combination, appear to indicate placental dysfunction that is associated with the development of severe preeclampsia.

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Background: The diagnosis of breast cancer, in combination with the anticipation of surgery, evokes fear, uncertainty, and anxiety in most women. Objective: Study purposes were to examine in patients who underwent breast cancer surgery how ratings of state anxiety changed from the time of the preoperative assessment to 6 months after surgery and to investigate whether specific demographic, clinical, symptom, and psychosocial adjustment characteristics predicted the preoperative levels of state anxiety and/or characteristics of the trajectories of state anxiety. Interventions/Methods: Patients (n = 396) were enrolled preoperatively and completed the Spielberger State Anxiety inventory monthly for 6 months. Using hierarchical linear modeling, demographic, clinical, symptom, and psychosocial adjustment characteristics were evaluated as predictors of initial levels and trajectories of state anxiety. Results: Patients experienced moderate levels of anxiety before surgery. Higher levels of depressive symptoms and uncertainty about the future, as well as lower levels of life satisfaction, less sense of control, and greater difficulty coping, predicted higher preoperative levels of state anxiety. Higher preoperative state anxiety, poorer physical health, decreased sense of control, and more feelings of isolation predicted higher state anxiety scores over time. Conclusions: Moderate levels of anxiety persist in women for 6 months after breast cancer surgery. Implications for Practice: Clinicians need to implement systematic assessments of anxiety to identify high-risk women who warrant more targeted interventions. In addition, ongoing follow-up is needed to prevent adverse postoperative outcomes and to support women to return to their preoperative levels of function.

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Purpose The purpose of this secondary analysis was to determine changes in physical inactivity from baseline to 5 years and to identify factors associated with and predictive of physical inactivity among individuals with type 2 diabetes enrolled in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study. DIAD was a prospective randomized screening trial that assessed the prevalence of silent ischemia in asymptomatic patients with type 2 diabetes. Subjects were recruited from diabetes and primary care practices at 14 centers throughout the United States and Canada. This is a secondary data analysis of the physical activity data (type and hours/week) collected. No intervention was conducted. In all subjects, physical inactivity rose from 24% at baseline to 33% at 5 years (S = 28.93; P <.0001). This change was significant in both men (S = 11.44; P <.0001), increasing from 23% to 31%, and women (S = 18.05; P <.0001), increasing from 25% to 36%. Gender differences were noted in several factors associated with baseline physical inactivity as well as in factors predictive of physical inactivity at 5 years. Important factors associated at both time points included lower level of education, current employment, presence of peripheral and autonomic neuropathy, and indicators of overweight/obesity. Baseline physical inactivity was strongly predictive of physical inactivity at 5 years (odds ratio, 3.27; 95% confidence interval, 2.36-4.54; P <.0001). Gender-related differences were noted in factors associated with and predictive of physical inactivity.

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Intermittent dosing for pre-exposure prophylaxis (PrEP) has been proposed as an alternative to daily PrEP to reduce cost and patient drug exposure and to improve adherence. One possible dosing regimen is pre-intercourse PrEP, which requires anticipating sex in advance. We examined preferences for daily versus pre-intercourse PrEP and ability to anticipate sex among 310 HIV uninfected members of HIV serodiscordant heterosexual couples in Thika, Kenya, with high HIV knowledge and experience with daily PrEP use in a clinical trial setting. Preferences were evenly split between daily PrEP (47.4 %) and pre-intercourse PrEP (50.7 %). Participants were more likely to prefer daily PrEP if they reported unprotected sex during the prior month (adjusted prevalence ratio [aPR] 1.48, 95 % CI 1.20-1.81) or <80 % adherence to study drug (aPR 1.50, 95 % CI 1.25-1.79), and were less likely to prefer daily PrEP if sex was usually planned, versus spontaneous (aPR 0.76, 95 % CI 0.61-0.96). A minority (24.2 %) reported anticipating sex >3 h in advance, with younger participants being less likely to do so (aPR 0.43, 95 % CI 0.23-0.83 for ages 18-29 vs. ≥40). Findings suggest that intermittent PrEP could be a popular option in this population, but that optimal adherence and sufficient drug levels might be challenging with a pre-intercourse regimen.

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Subgroups of individuals may be at greater risk of cytokine-induced changes in attentional function. The purposes of this study were to identify subgroups of individuals with distinct trajectories of attentional function and evaluate for phenotypic and genotypic (i.e., cytokine gene polymorphisms) differences among these subgroups. Self-reported attentional function was evaluated in 252 participants (167 oncology patients and 85 family caregivers) using the Attentional Function Index before radiation therapy and at six additional assessments over 6 months. Three latent classes of attentional function were identified using growth mixture modeling: moderate (36.5%), moderate-to-high (48.0%), and high (15.5%) attentional function. Participants in the moderate class were significantly younger, with more comorbidities and lower functional status, than those in the other two classes. However, only functional status remained significant in multivariable models. Included in the genetic association analyses were 92 single nucleotide polymorphisms (SNPs) among 15 candidate genes. Additive, dominant, and recessive genetic models were assessed for each SNP. Controlling for functional status, only Interleukin 6 (IL6) rs1800795 remained a significant genotypic predictor of class membership in multivariable models. Each additional copy of the rare "G" allele was associated with a 4-fold increase in the odds of belonging to the lower attentional function class (95% confidence interval: [1.78, 8.92]; p = .001). Findings provide preliminary evidence of subgroups of individuals with distinct trajectories of attentional function and of a genetic association with an IL6 promoter polymorphism.

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Background: Advances in cancer treatments continue to reduce the incidence of lymphedema. Yet, many breast cancer survivors still face long-term postoperative challenges as a result of developing lymphedema. The purpose of this study was to preliminarily evaluate The Optimal Lymph Flow program, a patient-centered education and behavioral program focusing on self-care strategies to enhance lymphedema risk reduction by promoting lymph flow and optimize body mass index (BMI). Methods: A prospective, longitudinal, quasi-experimental design with repeated-measures was used. The study outcomes included lymph volume changes by infrared perometer, and BMI by a bioimpedance device at pre-surgery baseline, 2–4 weeks after surgery, 6-month and 12-month follow-up. A total of 140 patients were recruited and participated in The Optimal Lymph Flow program; 134 patients completed the study with 4 % attrition rate. Results: Fifty-eight percent of patients had axillary node dissection and 42 % had sentinel lymph node biopsy (SLNB). The majority (97 %) of patients maintained and improved their preoperative limb volume (LV) and BMI at the study endpoint of 12 months following cancer surgery. Cumulatively, two patients with SLNB and two patients with axillary lymph node dissection had measurable lymphedema (>10 % LV change). At the 12-month follow-up, among the four patients with measurable lymphedema, two patients’ LV returned to preoperative level without compression therapy but by maintaining The Optimal Lymph Flow exercises to promote daily lymph flow. Conclusions: This educational and behavioral program is effective in enhancing lymphedema risk reduction. The study provided initial evidence for emerging change in lymphedema care from treatment-focus to proactive risk reduction.

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Background: Outcome expectancy may play an important role in behavior change. Previous studies tested the validity and the reliability of the Perceived Therapeutic Efficacy Scale (PTES), a scale that measures outcome expectancy related to adhering to a cholesterol-lowering diet. Further study was needed to examine its psychometric properties in a larger sample. Objective: The aim of this study was to test the psychometric properties of the 10-item PTES in a large sample. Methods: The PTES and the Connor Diet Habit Survey were administered to adults enrolled in a cardiac rehabilitation program. Results: The final sample for the analysis (N = 224) was, on average, 69.35 years old and was predominantly men (66.50%) and white (92.40%); nearly all (96.00%) completed high school. The inter-item correlation matrix revealed that correlation coefficients were greater than 0.80 between 4 pairs of items, suggesting that the 4 items were redundant. After consulting with a content expert and an examination of item content, we removed the 4 redundant items (items 2, 3, 4, and 10) and reduced the scale to 6 items. Principal component analysis revealed a 1-factor scale with high loadings for the 6 items, each greater than 0.70. The reliability of the scale, measured by Cronbach's α, was 0.91. The total PTES score had a moderate correlation with self-reported behaviors of adhering to a cholesterol-lowering diet, as measured by the Connor Diet Habit Survey subscale for cholesterol and fat intake (r = 0.36, P < 0.05). Conclusions: This study demonstrated that the revised and shortened PTES scale is reliable and valid to measure outcome expectancy related to adhering to a cholesterol-lowering diet.

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Objective. To evaluate the association between clinical and demographic factors and health-related quality of life (HRQOL) among older people with multiple sclerosis (MS). Design. Cross-sectional survey-based study. Setting and participants. Patients with MS aged 60 years or older were recruited from 4 MS centers in Long Island, NY. Patients with severe cognitive impairment as determined by the health care practitioner were excluded. Participants were asked to complete 3 surveys at 3 different time-points. In the first survey, participants completed the Morisky Medication Adherence Scale and the Patient Multiple Sclerosis Neuropsychological Screening Questionnaire (P-MSNQ). The second survey was the Multiple Sclerosis Quality of Life-54 (MSQOL-54), and the third survey included the Beck Depression Inventory-II (BDI-II) and a disability status self-assessment scale. Cognitive function was measured at the time of recruitment using the Symbol Digit Modalities Test (SDMT). Analysis. The Andersen Healthcare Utilization model was used to structure the multivariate regression analysis. This model identifies multiple domains affecting quality of life, and the variables from the surveys were categorized according to domain: predisposing characteristics (demographic variables), enabling resources (caregiver support and living situation), needs (eg, health-related measures), and health behaviors (medication use, adherence). Main results. A total of 211 completed the first survey, 188 the second, and 179 the third. 80% were female and 95% were white. Average age was 65.5 (SD 5.6) years. 56% of respondents' self-reported scores on the SDMT classified them as cognitively impaired. Risk of neuropsychological impairment, depression, and disability status were significantly associated with a decreased mental and physical HRQOL. Significantly, there was a strong association between predisposing characteristics and QOL. Being widowed and remaining employed were the strongest predictors of better physical QOL and having an education level of high school or less was a predictor of lower mental HRQOL. Conclusion. Clinicians should measure HRQOL in older MS patients regularly and assess for depression and cognitive impairment.

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Objectives To examine racial and ethnic differences in the effects of body mass index (BMI) on the onset of functional impairment over 10 years of follow-up. Design Longitudinal analyses of a cohort from a nationally representative survey of community-dwelling American adults. Setting Six waves (1996-2006) of the Health and Retirement Study (HRS). Participants Two groups of HRS participants aged 50 and older without functional impairment at baseline (1996): 5,884 with no mobility difficulty and 8,484 with no activity of daily living (ADL) difficulty. Measurements Mobility difficulty was a composite measure of difficulty walking several blocks, walking one block, climbing several flights of stairs, and climbing one flight of stairs. ADL difficulty was measured as difficulty in dressing, bathing or showering, eating, and getting in and out of bed without help. The association between baseline BMI and risk of developing functional impairment was estimated using generalized estimating equation models. Results Overweight and obesity were significant predictors of functional impairment. Overweight and obese Hispanics were 41% and 91% more likely, respectively, to develop ADL disability than whites in the same BMI categories. Overweight and severely obese blacks were also more likely than their white counterparts to develop ADL disability. Risk of developing ADL difficulty was higher for Hispanics than for blacks in the obese category. No significant differences in onset of mobility difficulty were found between racial or ethnic groups within any BMI category. Conclusion Blacks and Hispanics were at higher risk than whites of ADL but not mobility impairment. In addition to weight control, prevention efforts should promote exercise to reduce functional impairment, especially for blacks and Hispanics, who are at higher risk.

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Purpose: Insulin resistance is believed to play an important role in the link between energy imbalance and colon carcinogenesis. Emerging evidence suggests that there are substantial racial differences in genetic and anthropometric influences on insulin-like growth factors (IGFs); however, few studies have examined racial differences in the associations of IGFs and colorectal adenoma, precursor lesions of colon cancer. Methods: We examined the association of circulating levels of IGF-1, IGFBP-3 and IGFBP-1, and SNPs in the IGF-1 receptor (IGF1R), IGF-2 receptor (IGF2R), and insulin receptor genes with risk of adenomas in a sample of 410 incident adenoma cases and 1,070 controls from the Case Transdisciplinary Research on Energetics and Cancer (TREC) Colon Adenomas Study. Results: Caucasians have higher IGF-1 levels compared to African Americans; mean IGF-1 levels are 119.0 ng/ml (SD = 40.7) and 109.8 ng/ml (SD = 40.8), respectively, among cases (p = 0.02). Mean IGF-1 levels are also higher in Caucasian controls (122.9 ng/ml, SD = 41.2) versus African American controls (106.9, SD = 41.2), p = 0.001. We observed similar differences in IGFBP3 levels by race. Logistic regression models revealed a statistically significant association of IGF-1 with colorectal adenoma in African Americans only, with adjusted odds ratios (ORs) of 1.68 (95 % CI 1.06-2.68) and 1.68 (95 % CI 1.05-2.71), respectively, for the second and third tertiles as compared to the first tertile. One SNP (rs496601) in IGF1R was associated with adenomas in Caucasians only; the per allele adjusted OR is 0.73 (95 % CI 0.57-0.93). Similarly, one IGF2R SNP (rs3777404) was statistically significant in Caucasians; adjusted per allele OR is 1.53 (95 % CI 1.10-2.14). Conclusion: Our results suggest racial differences in the associations of IGF pathway biomarkers and inherited genetic variance in the IGF pathway with risk of adenomas that warrant further study.

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Objective: To assess racial/ethnic disparities in preventive care practices among U.S. nursing home residents. Method: To implement the Institute of Medicine definition of health care disparity, we used the rank-and-replace adjustment method to assess the disparity in receipt of eight preventive care services among residents and evaluate trends in disparities. The sampling design (stratification and clustering) was accounted for using Stata 11. Results: The 2004 National Nursing Home Surveys data show White residents were more likely to have pain management, scheduled toilet plan/bladder retraining, influenza vaccination, and pneumococcal vaccination than Black residents. White residents were also more likely to have scheduled toilet plan/bladder retraining than residents of Other race/ethnicity. Significant Black-White disparities in receipt of influenza vaccination and pneumococcal vaccination were found. Time trend analysis showed that disparities were neither exacerbated nor reduced. Conclusion: Persistent racial/ethnic disparities in preventive care among nursing home residents exist. We urge the development and implementation of targeted interventions to improve the quality of preventive care in nursing homes.

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Puerto Rico (PR) has a large and rapidly growing population of people living with HIV. However, relatively little behavioral or clinical research has been done in this population. As treatment for HIV increasingly moves into a chronic condition model, it is becoming increasingly important to understand the needs of this population so critical social and behavioral interventions can be developed, thus enabling the individual and community-level benefits of antiretroviral (ARV) treatment to be fully realized. To date, however, there has been very little research on the mental health needs of people living with HIV in PR, a fact that constrains intervention development and implementation. This paper describes data from a public sexually transmitted infection (STI) and HIV clinic study in the San Juan metropolitan area between April 2010 and December 2012 (n = 1185), roughly a third (36%) of whom are living with HIV. Descriptive statistics, chi-square, t-tests, and binary logistic regressions were used to assess associations between HIV status and a history of suicide attempt. The overall prevalence of a history of suicide attempt was 20.4%. No statistically significant relationship was found between a history of suicide attempt and being HIV positive, although people with HIV infection did evidence a higher prevalence of attempts than HIV-negative subjects (23.4% vs. 19.0%). Factors associated with having a history of suicide attempt within the overall sample included gender, current employment status, a lifetime history of drug use, and a lifetime history of sex work. Similar patterns were seen in the HIV-positive subsample. There was a nonsignificant trend toward increased risk for a post-diagnosis suicide attempt. These findings suggest that additional research on mental health risks among populations at risk for HIV in PR is needed.

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OBJECTIVE: We sought to examine the association between increased first-trimester fetal nuchal translucency (NT) measurement and major noncardiac structural birth defects in euploid infants. STUDY DESIGN: Included were 75,899 singleton infants without aneuploidy or critical congenital heart defects born in California in 2009 through 2010 with NT measured between 11-14 weeks of gestation. Logistic binomial regression was employed to estimate relative risks (RRs) and 95% confidence intervals (CIs) for occurrence of birth defects in infants with an increased NT measurement (by percentile at crown-rump length [CRL] and by ≥3.5 mm compared to those with measurements <90th percentile for CRL). RESULTS: When considered by CRL adjusted percentile and by measurement ≥3.5 mm, infants with a NT ≥95th percentile were at risk of having ≥1 major structural birth defects (any defect, RR, 1.6; 95% CI, 1.3-1.9; multiple defects, RR, 2.1; 95% CI, 1.3-3.4). Infants with a NT measurement ≥95th percentile were at particularly high risk for pulmonary, gastrointestinal, genitourinary, and musculoskeletal anomalies (RR, 1.6-2.7; 95% CI, 1.1-5.4). CONCLUSION: Our findings demonstrate that risks of major pulmonary, gastrointestinal, genitourinary, and musculoskeletal structural birth defects exist for NT measurements ≥95th percentile. The ≥3-fold risks were observed for congenital hydrocephalus; agenesis, hypoplasia, and dysplasia of the lung; atresia and stenosis of the small intestine; osteodystrophies; and diaphragm anomalies.

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Background: Single nucleotide polymorphisms (SNPs) in the Ryanodine receptor 3 (RYR3) gene are associated with common carotid intima media thickness (CCA cIMT) in HIV-infected men. We evaluated SNPs in the RYR3 gene among HIV-infected women participating in Women's Interagency HIV Study (WIHS). Methods: CCA cIMT was measured using B-mode ultrasound and the 838 SNPs in the RYR3 gene region were genotyped using the Illumina HumanOmni2.5-quad beadchip. The CCA cIMT genetic association was assessed using linear regression analyses among 1213 women and also separately among White (n=139), Black (n=720) and Hispanic (n=354) women after adjusting for confounders. A summary measure of pooled association was estimated using a meta-analytic approach by combining the effect estimates from the three races. Haploblocks were inferred using Gabriel's method and haplotype association analyses were conducted among the three races separately. Results: SNP rs62012610 was associated with CCA cIMT among the Hispanics (p=4.41×10-5), rs11856930 among Whites (p=5.62×10-4), and rs2572204 among Blacks (p=2.45×10-3). Meta-analysis revealed several associations of SNPs in the same direction and of similar magnitude, particularly among Blacks and Hispanics. Additionally, several haplotypes within three haploblocks containing SNPs previously related with CCA cIMT were also associated in Whites and Hispanics. Discussion: Consistent with previous research among HIV-infected men, SNPs within the RYR3 region were associated with subclinical atherosclerosis among HIV-infected women. Allelic heterogeneity observed across the three races suggests that the contribution of the RYR3 gene to CCA cIMT is complex, and warrants future studies to better understand regional SNP function.