[Show abstract][Hide abstract] ABSTRACT: sec> Background: For women with hormone receptor–positive, operable breast cancer, surgical oophorectomy plus tamoxifen is an effective adjuvant therapy. We conducted a phase III randomized clinical trial to test the hypothesis that oophorectomy surgery performed during the luteal phase of the menstrual cycle was associated with better outcomes. Methods: Seven hundred forty premenopausal women entered a clinical trial in which those women estimated not to be in the luteal phase of their menstrual cycle for the next one to six days (n = 509) were randomly assigned to receive treatment with surgical oophorectomy either delayed to be during a five-day window in the history-estimated midluteal phase of the menstrual cycles, or in the next one to six days. Women who were estimated to be in the luteal phase of the menstrual cycle for the next one to six days (n = 231) were excluded from random assignment and received immediate surgical treatments. All patients began tamoxifen within 6 days of surgery and continued this for 5 years. Kaplan-Meier methods, the log-rank test, and multivariable Cox regression models were used to assess differences in five-year disease-free survival (DFS) between the groups. All statistical tests were two-sided. Results: The randomized midluteal phase surgery group had a five-year DFS of 64%, compared with 71% for the immediate surgery random assignment group (hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 0.91 to 1.68, P = .18). Multivariable Cox regression models, which included important prognostic variables, gave similar results (aHR = 1.28, 95% CI = 0.94 to 1.76, P = .12). For overall survival, the univariate hazard ratio was 1.33 (95% CI = 0.94 to 1.89, P = .11) and the multivariable aHR was 1.43 (95% CI = 1.00 to 2.06, P = .05). Better DFS for follicular phase surgery, which was unanticipated, proved consistent across multiple exploratory analyses. Conclusions: The hypothesized benefit of adjuvant luteal phase oophorectomy was not shown in this large trial. </sec
JNCI Journal of the National Cancer Institute 06/2015; 107(6). DOI:10.1093/jnci/djv064 · 15.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To test the effectiveness of a colorectal cancer (CRC) screening intervention directed at three levels (clinic, provider, patient) in a primary care setting.
We conducted a group randomized trial (Clinical Trials registration no. NCT01568151) among 10 primary care clinics in Columbus, Ohio that were randomized to a study condition (intervention or usual care). We determined the effect of a multi-level, stepped behavioral intervention on receipt of a CRC screening test among average-risk patients from these clinics over the study period.
Patients (n=527) who were outside of CRC screening recommendations were recruited. Overall, 35.4% of participants in the intervention clinics had received CRC screening by the end of the study compared to 35.1% of participants who were in the usual care clinics. Time to CRC screening was also similar across arms (HR=0.97, 95% CI=0.65-1.45).
The multi-level intervention was not effective in increasing CRC screening among participants who needed a test, perhaps due to low participation of patients in the stepped intervention. Future studies utilizing evidence-based strategies to encourage CRC screening are needed.
[Show abstract][Hide abstract] ABSTRACT: Patient navigation (PN) may reduce cancer health disparities. Few studies have investigated the effects of PN on patient-reported satisfaction with care or assessed patients’ satisfaction with navigators. The objectives of this study are to test the effects of PN on patient satisfaction with cancer care, assess patients’ satisfaction with navigators, and examine the impact of barriers to care on satisfaction for persons with abnormal cancer-related screening tests or symptoms. Study participants included women and men with abnormal breast, cervical, or colorectal cancer screening tests and/or symptoms receiving care at 18 clinics. Navigated (n = 416) and non-navigated (n = 292) patients completed baseline and end-of-study measures. There was no significant difference between navigated and non-navigated patients in change in patient satisfaction with cancer care from baseline to exit. African-American (p p = 0.03), low income (p p p = 0.04), with full-time employment showing the most improvement. The interaction between satisfaction with navigators and satisfaction with care over time was marginally significant (p = 0.08). Baseline satisfaction was lower for patients who reported a barrier to care (p = 0.02). Patients reporting other-focused barriers (p = 0.03), including transportation (p = 0.02), had significantly lower increases in satisfaction over time. Overall, results suggested that assessing barriers to cancer care and tailoring navigation to barrier type could enhance patients’ experiences with health care. PN may have positive effects for healthcare organizations struggling to enhance quality of care.
Journal of Cancer Education 12/2014; DOI:10.1007/s13187-014-0772-1 · 1.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Research shows that multilevel factors influence healthcare delivery and patient outcomes. The study goal was to examine how clinic type (academic medical center (AMC) or federally-qualified health center (FQHC)) and patient characteristics influence time to resolution (TTR) among individuals with an abnormal cancer screening test enrolled in a patient navigation (PN) intervention. Methods: Data were obtained from the Ohio Patient Navigation Research Project, a group-randomized trial of 862 patients from 18 clinics in Columbus, Ohio. Patient's TTR after an abnormal breast, cervical, or colorectal screening test and the clinics' patient and provider characteristics were obtained. Descriptive statistics and Cox shared frailty proportional hazards regression models of TTR were used. Results: The mean patient age was 44.8 years and 71% of patients were white. In models adjusted for study arm, FQHC patients had a 39% lower rate of resolution than AMC patients (P=0.004). Patient factors of having a college education, private insurance, higher income, and being older were significantly associated with lower TTR. After adjustment for factors that substantially impacted the effect of clinic type (patient insurance status, education level and age), clinic type was not significantly associated with TTR. Conclusions: These results suggest that TTR among individuals participating in PN programs is influenced by multiple socioeconomic patient-level factors rather than clinic type. Consequently, PN interventions should be tailored to address SES factors that influence TTR. Impact: These results provide clues regarding where to target PN interventions and the importance of recognizing predictors of TTR according to clinic type.
[Show abstract][Hide abstract] ABSTRACT: Background and Purpose
Individuals with Huntington's disease (HD) experience balance and gait problems that lead to falls. Clinicians currently have very little information about the reliability and validity of outcome measures to determine the efficacy of interventions that aim to reduce balance and gait impairments in HD. This study examined the reliability and concurrent validity of spatiotemporal gait measures, the Tinetti Mobility Test (TMT), Four Square Step Test (FSST), and Activities-Specific Balance Confidence (ABC) Scale in individuals with HD.
Participants with HD [n = 20; mean age± SD =50.9 ± 13.7; 7 male] were tested on spatiotemporal gait measures and the TMT, FSST, and ABC Scale before and after a six week period to determine test-retest reliability and minimal detectable change (MDC) values. Linear relationships between gait and clinical measures were estimated using Pearson's correlation coefficients.
Spatiotemporal gait measures, the TMT total and the FSST showed good to excellent test-retest reliability (ICC > 0.75). MDC values were 0.30 m/s and 0.17 m/s for velocity in forward and backward walking respectively, four points for the TMT, and three seconds for the FSST. The TMT and FSST were highly correlated with most spatiotemporal measures. The ABC Scale demonstrated lower reliability and less concurrent validity than other measures.
The high test-retest reliability over a six week period and concurrent validity between the TMT, FSST, and spatiotemporal gait measures suggests that the TMT and FSST may be useful outcome measures for future intervention studies in ambulatory individuals with HD.
[Show abstract][Hide abstract] ABSTRACT: XPO1/CRM1 is a key nuclear exporter protein that mediates translocation of numerous cellular regulatory proteins. We investigated whether XPO1 is a potential therapeutic target in melanoma using novel selective inhibitors of nuclear export (SINE). In vitro effects of SINE on cell growth and apoptosis were measured by MTS assay and flow cytometry [Annexin V/propidium iodide (PI)], respectively in human metastatic melanoma cell lines. Immunoblot analysis was used to measure nuclear localization of key cellular proteins. The in vivo activity of oral SINE was evaluated in NOD/SCID mice bearing A375 or CHL-1 human melanoma xenografts. SINE compounds induced cytostatic and pro-apoptotic effects in both BRAF wild type and mutant (V600E) cell lines at nanomolar concentrations. The cytostatic and pro-apoptotic effects of XPO1 inhibition were associated with nuclear accumulation of TP53, and CDKN1A induction in the A375 cell line with wild type TP53, while pMAPK accumulated in the nucleus regardless of TP53 status. The orally bioavailable KPT-276 and KPT-330 compounds significantly inhibited growth of A375 (p<0.0001) and CHL-1 (p = 0.0087) human melanoma cell lines in vivo at well tolerated doses. Inhibition of XPO1 using SINE represents a potential therapeutic approach for melanoma across cells with diverse molecular phenotypes by promoting growth inhibition and apoptosis.
PLoS ONE 07/2014; 9(7):e102983. DOI:10.1371/journal.pone.0102983 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dietary lipids have been shown to increase bioavailability of provitamin A carotenoids from a single meal, but the effects of dietary lipids on conversion to vitamin A during absorption are essentially unknown. Based on previous animal studies, we hypothesized that the consumption of provitamin A carotenoids with dietary lipid would enhance conversion to vitamin A during absorption compared with the consumption of provitamin A carotenoids alone. Two separate sets of 12 healthy men and women were recruited for 2 randomized, 2-way crossover studies. One meal was served with fresh avocado (Persea americana Mill), cultivated variety Hass (delivering 23 g of lipid), and a second meal was served without avocado. In study 1, the source of provitamin A carotenoids was a tomato sauce made from a novel, high-β-carotene variety of tomatoes (delivering 33.7 mg of β-carotene). In study 2, the source of provitamin A carotenoids was raw carrots (delivering 27.3 mg of β-carotene and 18.7 mg of α-carotene). Postprandial blood samples were taken over 12 h, and provitamin A carotenoids and vitamin A were quantified in triglyceride-rich lipoprotein fractions to determine baseline-corrected area under the concentration-vs.-time curve. Consumption of lipid-rich avocado enhanced the absorption of β-carotene from study 1 by 2.4-fold (P < 0.0001). In study 2, the absorption of β-carotene and α-carotene increased by 6.6- and 4.8-fold, respectively (P < 0.0001 for both). Most notably, consumption of avocado enhanced the efficiency of conversion to vitamin A (as measured by retinyl esters) by 4.6-fold in study 1 (P < 0.0001) and 12.6-fold in study 2 (P = 0.0013). These observations highlight the importance of provitamin A carotenoid consumption with a lipid-rich food such as avocado for maximum absorption and conversion to vitamin A, especially in populations in which vitamin A deficiency is prevalent. This trial was registered at clinicaltrials.gov as NCT01432210.
Journal of Nutrition 06/2014; 144(8). DOI:10.3945/jn.113.187674 · 4.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: sec> Background Limited data are available on the association between colorectal cancer (CRC) worry and CRC screening uptake, particularly in rural and underserved populations where there is an excess burden of CRC. Methods Between September 2009 and March 2010, we conducted a cross-sectional study among a randomly selected sample of Appalachian Ohio residents aged 51–75 years ( n = 1084). We also reviewed their medical records. Multivariable-adjusted models examined the association between CRC worry and screening by medical record review, assessed effect modification by CRC worry and determined the correlates of higher CRC worry. Results Approximately 50% of participants were adherent to CRC screening guidelines. There was no significant association between higher CRC worry and screening adherence [odds ratio (OR) = 1.32, 95% confidence interval (CI): 0.86–2.02]. CRC worry did not modify the association between any covariate and screening adherence. Participants who were unemployed/disabled (OR = 2.15, 95% CI: 1.34–3.45) and had higher CRC risk perception (OR = 3.49, 95% CI: 2.19–5.56) had higher odds of moderate-to-extreme worry. Conclusions These findings highlight the need for meaningful exploration of why higher CRC worry is not associated with adherence to CRC screening, particularly in rural, medically underserved populations. Development and implementation of interventions to increase CRC screening in such areas is a significant public health priority. </sec
Journal of Public Health 05/2014; 37(2). DOI:10.1093/pubmed/fdu031 · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patient navigation (PN) is a system-level strategy to decrease cancer mortality rates by reducing barriers to cancer care. Barriers to resolution among participants in the PN intervention arm with a breast or cervical abnormality in the Patient Navigation Research Program and navigators' actions to address those barriers were examined.
Data from seven institutions (2005-2010) included 1,995 breast and 1,194 cervical patients. A stratified Cox proportional hazards regression model was used to examine the effects of barriers on time to resolution of an abnormal screening test or clinical finding.
The range of unique barriers was 0 to 12 and 0 to 7 among participants with breast and cervical abnormalities, respectively. About two thirds of breast and one half of cervical participants had at least one barrier resulting in longer time to diagnostic resolution among breast (adjusted hazard ratio [HR], 0.744; p < .001) and cervical (adjusted HR, 0.792; p < .001) participants. Patient- and system-level barriers were most common. Frequent navigator actions were making arrangements, scheduling appointments, referrals, and education.
Having a barrier resulted in a delay in diagnostic resolution of an abnormal screening test or clinical finding. Health care systems can use these findings to improve existing PN programs or when developing new programs.
Women s Health Issues 01/2014; 24(1):e155-e162. DOI:10.1016/j.whi.2013.10.010 · 1.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: While tamoxifen activity is mainly due to endoxifen and the concentration of this active metabolite is, in part, controlled by CYP2D6 metabolic status, clinical correlative studies have produced mixed results.
In an exploratory study, we determined the CYP2D6 metabolic status and plasma concentrations of endoxifen among 224 Filipino and Vietnamese women participating in a clinical trial of adjuvant hormonal therapy for operable breast cancer. We further conducted a nested-case-control study among 48 women (half with recurrent disease, half without) investigating the relationship of endoxifen concentrations and recurrence of disease. We found a significant association of reduced endoxifen plasma concentrations with functionally important CYP2D6 genotypes. High endoxifen concentrations were associated with higher risk of recurrence; with a quadratic trend fitted to a stratified Cox proportional hazards regression model, the likelihood ratio p-value was 0.002. The trend also showed that in 8 out of 9 pairs with low endoxifen concentrations, the recurrent case had lower endoxifen levels than the matched control.
This exploratory analysis suggests that there is an optimal range for endoxifen concentrations to achieve favorable effects as adjuvant therapy. In particular, at higher concentrations (>70 ng.ml), endoxifen may promote recurrence.
[Show abstract][Hide abstract] ABSTRACT: Epidemiological studies support a link between cumulative sun exposure and cutaneous squamous cell carcinoma (SCC) development. However, the presumed effects of extended ultraviolet light B (UVB) exposure on tumorigenesis in the sexes have not been formally investigated. We examined differences in ultimate tumorigenesis at 25 weeks in mice exposed to UVB for either 10 or 25 weeks. Additionally, we investigated the effect of continued UVB exposure on the efficacy of topical treatment with anti-inflammatory (diclofenac) or antioxidant (C E Ferulic or vitamin E) compounds on modulating tumorigenesis. Vehicle-treated mice in the 25-week UVB exposure model exhibited an increased tumor burden and a higher percentage of malignant tumors compared to mice in the 10-week exposure model, which correlated with increases in total and mutant p53-positive epidermal cells. Only topical diclofenac decreased tumor number and burden in both sexes regardless of UVB exposure length. These data support the commonly assumed but not previously demonstrated fact that increased cumulative UVB exposure increases the risk of UVB-induced SCC development and can also affect therapeutic efficacies. Our study suggests that cessation of UVB exposure by at-risk patients may decrease tumor development and that topical NSAIDs such as diclofenac may be chemopreventive.