[Show abstract][Hide abstract] ABSTRACT: Risk assessment for prostate cancer is challenging due to its genetic heterogeneity. In this study, our goal was to develop an operational framework to select and evaluate gene variants that may contribute to familial prostate cancer risk. Drawing on orthogonal sources, we developed a candidate list of genes relevant to prostate cancer, then analyzed germline exomes from 12 case-only prostate cancer patients from high-risk families to identify patterns of protein-damaging gene variants. We described an average of 5 potentially disruptive variants in each individual and annotated them in the context of public databases representing human variation. Novel damaging variants were found in several genes of relevance to prostate cancer. Almost all patients had variants associated with defects in DNA damage response. Many also had variants linked to androgen signaling. Treatment of primary T-lymphocytes from these prostate cancer patients versus controls with DNA damaging agents showed elevated levels of the DNA double strand break (DSB) marker γH2AX (p < 0.05), supporting the idea of an underlying defect in DNA repair. This work suggests the value of focusing on underlying defects in DNA damage in familial prostate cancer risk assessment and demonstrates an operational framework for exome sequencing in case-only prostate cancer genetic evaluation.
[Show abstract][Hide abstract] ABSTRACT: Little is known about the impact of genetic and environmental risk assessment (GERA) feedback on colorectal cancer (CRC) screening. In a recently completed randomized trial, primary care patients received GERA feedback based on a blood test for genetic polymorphisms and serum folate level (GERA Group) versus usual care (Control Group). Subsequently, participants were offered CRC screening. Among participants who received GERA feedback, being at elevated risk was negatively associated with prospective CRC screening adherence. Secondary analyses of data from this study were performed to identify independent predictors of adherence among participants who received GERA feedback. We obtained baseline survey, follow-up survey, and endpoint medical records data on sociodemographic background, knowledge, psychosocial characteristics, risk status, and adherence for 285 GERA Group participants. Univariate and multivariable analyses were performed to identify predictors of CRC screening adherence. Following a 6-month outcomes observation period, we also conducted two focus groups with GERA Group participants to assess their perceptions of GERA risk feedback and screening. Content analyses of focus group data were evaluated to gain insights into participant response to risk feedback. Overall, half of GERA Group participants adhered to screening within 6 months after randomization. Multivariable analyses showed a statistically significant interaction between race and GERA feedback status relative to screening adherence (p = 0.043). Among participants who received average risk feedback, adherence was comparable among whites (49.7 %) and nonwhites (54.1 %); however, among those at elevated risk, adherence was substantially higher among whites (66.7 %) compared to nonwhites (33.3 %). Focus group findings suggest that whites were more likely than nonwhites to view elevated risk feedback as a prompt to screen. In response to receiving elevated risk feedback, nonwhites were more likely than whites to report feeling anxiety about the likelihood of being diagnosed with CRC. Further research is needed to explore race-related CRC screening differences in response to GERA feedback.
Journal of Behavioral Medicine 03/2015; 38(5). DOI:10.1007/s10865-015-9626-5 · 3.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Results: Overall screening rates for CRC did not statistically significantly differ between the usual care (35.7%) and GERA (33.1%) groups. After adjustment for baseline participant factors, the odds ratio for screening completion for GERA versus usual care was 0.88 (95% CI, 0.64 to 1.22). Within the GERA group, screening rates did not significantly differ between average-risk (38.1%) and elevated-risk (26.9%) participants. Odds ratios for elevated- versus average-risk participants remained nonsignificant after adjustment for covariates (odds ratio, 0.75 [CI, 0.39 to 1.42]). Limitation: Only 1 personalized genetic and environmental interaction and 1 health behavior (CRC screening) were assessed.
Annals of internal medicine 10/2014; 161(8):537-545. DOI:10.7326/M14-0765 · 17.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
This article describes the rigorous development process and initial feedback of the PRE-ACT (Preparatory Education About Clinical Trials) web-based- intervention designed to improve preparation for decision making in cancer clinical trials.
The multi-step process included stakeholder input, formative research, user testing and feedback. Diverse teams (researchers, advocates and developers) participated including content refinement, identification of actors, and development of video scripts. Patient feedback was provided in the final production period and through a vanguard group (N=100) from the randomized trial.
Patients/advocates confirmed barriers to cancer clinical trial participation, including lack of awareness and knowledge, fear of side effects, logistical concerns, and mistrust. Patients indicated they liked the tool's user-friendly nature, the organized and comprehensive presentation of the subject matter, and the clarity of the videos.
The development process serves as an example of operationalizing best practice approaches and highlights the value of a multi-disciplinary team to develop a theory-based, sophisticated tool that patients found useful in their decision making process. Practice implications Best practice approaches can be addressed and are important to ensure evidence-based tools that are of value to patients and supports the usefulness of a process map in the development of e-health tools.
[Show abstract][Hide abstract] ABSTRACT: Objective:
Among Chinese immigrant populations, increasing duration of US residence is associated with elevated risk for various chronic diseases. Although life-style changes after migration have been extensively studied in immigrant populations, the psychosocial impact of acculturative stress on biological markers of health is less understood. Thus, the purpose of the present study is to examine associations between acculturative stress and inflammatory markers in a Chinese immigrant population.
Study participants (n = 407 foreign-born Chinese American women) completed questionnaires assessing levels of stress, including acculturative stress and positive and negative life events in the previous year. Participant height and weight were measured using standard protocols, and blood samples were drawn for assessment of circulating serum levels of C-reactive protein (CRP) and soluble tumor necrosis factor receptor 2 (sTNFR2).
Higher levels of acculturative stress were significantly associated with higher levels of CRP (B = 0.07, 95% confidence interval = 0.01-0.13, p = .031) and sTNFR2 (B = 0.02, 95% confidence interval = 0.004-0.03, p = .012), adjusting for age and body mass index. The latter association was no longer statistically significant when overall acculturation (i.e., identification with American culture) was included in the model. Life events were not associated with CRP or sTNFR2.
This is one of the first studies to demonstrate that acculturative stress is associated with inflammatory markers in a Chinese immigrant population. Replication in other immigrant samples is needed to fully establish the biological correlates and clinical consequences of acculturative stress.
Psychosomatic Medicine 05/2014; 76(5). DOI:10.1097/PSY.0000000000000065 · 3.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neoadjuvant cisplatin-based chemotherapy is standard of care for muscle-invasive bladder cancer (MIBC); however, it is infrequently adopted in practice because of concerns regarding toxicity and delay to cystectomy. We hypothesized that three cycles of neoadjuvant accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) would be safe, shorten the time to surgery, and yield similar pathologic complete response (pT0) rates compared with historical controls.
Patients with cT2-T4a and N0-N1 MIBC were eligible and received three cycles of AMVAC with pegfilgrastim followed by radical cystectomy with lymph node dissection. The primary end point was pT0 rate. Telomere length (TL) and p53 mutation status were correlated with response and toxicity.
Forty-four patients were accrued; 60% had stage III to IV disease; median age was 64 years. Forty patients were evaluable for response, with 15 (38%; 95% CI, 23% to 53%) showing pT0 at cystectomy, meeting the primary end point of the study. Another six patients (14%) were downstaged to non-muscle invasive disease. Most (82%) experienced only grade 1 to 2 treatment-related toxicities. There were no grade 3 or 4 renal toxicities and no treatment-related deaths. One patient developed metastases and thus did not undergo cystectomy; all others (n = 43) proceeded to cystectomy within 8 weeks after last chemotherapy administration. Median time from start of chemotherapy to cystectomy was 9.7 weeks. TL and p53 mutation did not predict response or toxicity.
AMVAC is well tolerated and results in similar pT0 rates with 6 weeks of treatment compared with standard 12-week regimens. Further analysis is ongoing to ascertain whether molecular alterations in tumor samples can predict response to chemotherapy.
[Show abstract][Hide abstract] ABSTRACT: Patient participation in cancer clinical trials is low. Little is known about attitudinal barriers to participation, particularly among patients who may be offered a trial during an imminent initial oncology consult. The aims of the present study were to confirm the presence of proposed subscales of a recently developed cancer clinical trial attitudinal barriers measure, describe the most common cancer clinical trials attitudinal barriers, and evaluate socio-demographic, medical and financial factors associated with attitudinal barriers. A total of 1256 patients completed a survey assessing demographic factors, perceived financial burden, prior trial participation and attitudinal barriers to clinical trials participation. Results of a factor analysis did not confirm the presence of the proposed four attitudinal barriers subscale/factors. Rather, a single factor represented the best fit to the data. The most highly-rated barriers were fear of side-effects, worry about health insurance and efficacy concerns. Results suggested that less educated patients, patients with non-metastatic disease, patients with no previous oncology clinical trial participation, and patients reporting greater perceived financial burden from cancer care were associated with higher barriers. These patients may need extra attention in terms of decisional support. Overall, patients with fewer personal resources (education, financial issues) report more attitudinal barriers and should be targeted for additional decisional support.
European Journal of Cancer Care 01/2014; 24(1). DOI:10.1111/ecc.12180 · 1.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study used the Ottawa Decision Support Framework to evaluate a model examining associations between clinical trial knowledge, attitudinal barriers to participating in clinical trials, clinical trial self-efficacy, and clinical trial preparedness among 1256 cancer patients seen for their first outpatient consultation at a cancer center. As an exploratory aim, moderator effects for gender, race/ethnicity, education, and metastatic status on associations in the model were evaluated.
. Patients completed measures of cancer clinical trial knowledge, attitudinal barriers, self-efficacy, and preparedness. Structural equation modeling (SEM) was conducted to evaluate whether self-efficacy mediated the association between knowledge and barriers with preparedness.
. The SEM explained 26% of the variance in cancer clinical trial preparedness. Self-efficacy mediated the associations between attitudinal barriers and preparedness, but self-efficacy did not mediate the knowledge-preparedness relationship.
. Findings partially support the Ottawa Decision Support Framework and suggest that assessing patients' level of self-efficacy may be just as important as evaluating their knowledge and attitudes about cancer clinical trials.
Medical Decision Making 11/2013; 34(4). DOI:10.1177/0272989X13511704 · 3.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Caring for a relative or friend with cancer may be highly demanding and emotionally burdensome. Theory suggests that personal characteristics of a caregiver may contribute directly to a caregiver's emotional health. An underexplored variable is a caregiver's perception of choice in providing care to a relative or friend. Thus, this study sought to characterize perceived choice in providing care among family cancer caregivers and examine its association with emotional stress. This study is a secondary analysis of cross-sectional telephone interviews of 1,247 family caregivers, which included 104 cancer caregivers. The findings indicated that a high majority of cancer caregivers expressed elevated emotional stress. Most caregivers perceived themselves to have had a choice in providing care; however, a perceived lack of choice in providing care was significantly associated with greater emotional stress. Assessing clinical and policy-related strategies for alleviating concerns related to choice may be of value in the cancer context.
Western Journal of Nursing Research 11/2013; 36(6). DOI:10.1177/0193945913510211 · 1.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: For cancer patients offered clinical trials, treatment decisions may be especially complex as trials pose uncertain risks and benefits of new approaches. Many patients also have financial concerns, including those regarding insurance coverage. We hypothesize that financial concerns may affect a patient’s ability to make an informed, patient-centered decisions regarding clinical trials.
Method: PRE-ACT (PReparatory Education About Clinical Trials) is a web-based educational tool designed to increase cancer patients’ preparation for making decisions about clinical trial enrollment by delivering video content tailored to individuals’ knowledge gaps and attitudes assessed by baseline survey. We conducted a multicenter, randomized study of PRE-ACT vs. written generic clinical trials information. The baseline survey (5-point Likert scales) included questions regarding cost concerns: “How much of a burden on you is the cost of your medical care? (Q1)”, “I'm afraid that my health insurance won't pay for a clinical trial (Q2),” and “I’m worried that I wouldn’t be able to afford the costs of treatment on a clinical trial (Q3).” We summed results, with higher scores indicating greater financial concerns. Multiple linear regression was used to measure the association between concerns and self-reported measures of self-efficacy, preparation for decision making, distress and decisional conflict in separate models, controlling for sociodemographic characteristics. In secondary analyses, similar models were built using the cost questions (Q2 and 3) together and burden (Q1) alone.
Result: 1212 patients completed baseline surveys. 27% were 65 or older. 58% were female. 24% had high school education or less. Greater financial concern was associated with lower self-efficacy and preparation for decision making, and greater decisional conflict and distress, even after adjustment for age, race, gender, education, employment and hospital location (p<.0001 for all models). In the self-efficacy, preparation and distress models, age < 65, unemployment and lack of education past high school were also significantly associated with greater concerns (p<.05 for all models) . Similar findings were noted for secondary analyses, except that greater burden (Q3) was not associated with worse self-efficacy.
Conclusion: Financial concerns are associated with several psychological constructs that may negatively impact informed decision-making regarding clinical trial participation. Greater attention to patients’ financial needs and available resources may best help them make optimal treatment decisions that reflect their preferences and values.
The 35th Annual Meeting of the Society for Medical Decision Making; 10/2013