Optimal Integration of Behavioral Medicine into Clinical Genetics and Genomics.

Clinical genetics and genomics will exert their greatest population impact by leveraging the rich knowledge of human behavior that is central to the discipline of behavioral medicine. We contend that more concerted efforts are needed to integrate these fields synergistically, and accordingly, we consider barriers and potential actions to hasten such integration.

Perception of personalized medicine, pharmacogenomics, and genetic testing among undergraduates in Hong Kong.

BACKGROUND: The global development and advancement of genomic medicine in the recent decade has accelerated the implementation of personalized medicine (PM) and pharmacogenomics (PGx) into clinical practice, while catalyzing the emergence of genetic testing (GT) with relevant ethical, legal, and social implications (ELSI). RESULTS: The perception of university undergraduates with regards to PM and PGx was investigated, and 80% of undergraduates valued PM as a promising healthcare model with 66% indicating awareness of personal genome testing companies. When asked about the curriculum design towards PM and PGx, compared to undergraduates in non-medically related curriculum, those studying in medically related curriculum had an adjusted 7.2 odds of perceiving that their curriculum was well-designed for learning PGx (95% CI 3.6-14.6) and a 3.7 odds of perceiving that PGx was important in their study (95% CI 2.0-6.8). Despite this, only 16% of medically related curriculum undergraduates would consider embarking on future education on PM. When asked about their perceptions on GT, 60% rated their genetic knowledge as "School Biology" level or below while 76% would consider undergoing a genetic test. As for ELSI, 75% of undergraduates perceived that they were aware of ethical issues of GT in general, particularly on "Patient Privacy" (80%) and "Data Confidentiality" (68%). Undergraduates were also asked about their perceived reaction upon receiving an unfavorable result from GT, and over half of the participants perceived that they would feel "helpless or pessimistic" (56%), "inadequate or different" (59%), and "disadvantaged at job seeking" (59%), while older undergraduates had an adjusted 2.0 odds of holding the latter opinion (95% CI 1.1-3.5), compared to younger undergraduates. CONCLUSION: Hong Kong undergraduates showed a high awareness of PM but insufficient genetic knowledge and low interest in pursuing a career towards PM. They were generally aware of ethical issues of GT and especially concerned about patient privacy and data confidentiality. There was a predominance of pessimistic views towards unfavorable testing results. This study calls for the attention to evaluate education and talent development on genomics, and update existing legal frameworks on genetic testing in Hong Kong.

Behavioural Challenges Associated With Risk-Adapted Cancer Screening.

Cancer screening programmes have a major role in reducing cancer incidence and mortality. Traditional internationally-adopted protocols have been to invite all 'eligible individuals' for the same test at the same frequency. However, as highlighted in Cancer Research UK's 2020 strategic vision, there are opportunities to increase effectiveness and cost-effectiveness, and reduce harms of screening programmes, by making recommendations on the basis of personalised estimates of risk. In some respects, this extends current approaches of providing more intensive levels of care outside screening programmes to individuals at very high risk due to their family history or underlying conditions. However, risk-adapted colorectal cancer screening raises a wide range of questions, not only about how best to change existing programmes but also about the psychological and behavioural effects that these changes might have. Previous studies in other settings provide some important information but remain to be tested and explored further in the context of colorectal screening. Conducting behavioural science research in parallel to clinical research will ensure that risk-adapted screening is understood and accepted by the population that it aims to serve.

When physical activity meets the physical environment: precision health insights from the intersection.

BACKGROUND: The physical environment can facilitate or hinder physical activity. A challenge in promoting physical activity is ensuring that the physical environment is supportive and that these supports are appropriately tailored to the individual or group in question. Ideally, aspects of the environment that impact physical activity would be enhanced, but environmental changes take time, and identifying ways to provide more precision to physical activity recommendations might be helpful for specific individuals or groups. Therefore, moving beyond a "one size fits all" to a precision-based approach is critical. MAIN BODY: To this end, we considered 4 critical aspects of the physical environment that influence physical activity (walkability, green space, traffic-related air pollution, and heat) and how these aspects could enhance our ability to precisely guide physical activity. Strategies to increase physical activity could include optimizing design of the built environment or mitigating of some of the environmental impediments to activity through personalized or population-wide interventions. CONCLUSIONS: Although at present non-personalized approaches may be more widespread than those tailored to one person's physical environment, targeting intrinsic personal elements (e.g., medical conditions, sex, age, socioeconomic status) has interesting potential to enhance the likelihood and ability of individuals to participate in physical activity.

Barriers and facilitators to dissemination and adoption of precision medicine among Hispanics/Latinos.

BACKGROUND: With the rapid advances in gene technologies in recent years, the potential benefits of precision medicine (PM) may spread unevenly to disadvantaged populations, such as Hispanics/Latinos. The objective of this study was to explore patient-level barriers and facilitators to dissemination and adoption of PM among Hispanics/Latinos, including knowledge and awareness. METHODS: Self-identified Hispanics/Latinos from diverse countries in Latin America (N = 41) participated in the study. Using a cross-sectional observational qualitative research design, six focus groups and a demographic questionnaire were collected in English and Spanish. Qualitative content analysis was utilized to code the transcripts and identify emerging themes. RESULTS: Hispanics/Latinos never heard of and had no knowledge about PM. Barriers to dissemination and adoption of PM included lack of health insurance, financial burden, participants' immigration status, distrust of government, limited English proficiency, low literacy levels, cultural norms, fear about genetic testing results, lack of transportation, newness of PM, and lack of information about PM. Facilitators included family support; information provided in Spanish; use of plain language and graphics; assistance programs for uninsured; trust in physicians, healthcare staff, well-known hospitals, academic institutions, and health care providers and community organization as sources of reliable information; personal motivation, and altruism or societal benefit. CONCLUSIONS: Culturally-and linguistically-tailored, low-literacy educational material about PM should be created in English and Spanish. Future research should examine provider-level and system-level barriers and facilitators to implementation and adoption of PM among Hispanic/Latino patients.

Personalized medicine, digital technology and trust: a Kantian account.

Trust relations in the health services have changed from asymmetrical paternalism to symmetrical autonomy-based participation, according to a common account. The promises of personalized medicine emphasizing empowerment of the individual through active participation in managing her health, disease and well-being, is characteristic of symmetrical trust. In the influential Kantian account of autonomy, active participation in management of own health is not only an opportunity, but an obligation. Personalized medicine is made possible by the digitalization of medicine with an ensuing increased tailoring of diagnostics, treatment and prevention to the individual. The ideal is to increase wellness by minimizing the layer of interpretation and translation between relevant health information and the patient or user. Arguably, this opens for a new level of autonomy through increased participation in treatment and prevention, and by that, increased empowerment of the individual. However, the empirical realities reveal a more complicated landscape disturbed by information 'noise' and involving a number of complementary areas of expertise and technologies, hiding the source and logic of data interpretation. This has lead to calls for a return to a mild form of paternalism, allowing expertise coaching of patients and even withholding information, with patients escaping responsibility through blind or lazy trust. This is morally unacceptable, according to Kant's ideal of enlightenment, as we have a duty to take responsibility by trusting others reflexively, even as patients. Realizing the promises of personalized medicine requires a system of institutional controls of information and diagnostics, accessible for non-specialists, supported by medical expertise that can function as the accountable gate-keeper taking moral responsibility required for an active, reflexive trust.

The narrative paradox of the BRCA gene: an ethnographic study in the clinical encounters of ovarian cancer patients.

In this era of personalisation a patient's molecular profile plays an increasingly central role in development and delivery of personalised medicine. This paper sets out to explore the sociocultural implications of mainstreaming BRCA genetic testing in the treatment of advanced ovarian cancer patients, who carry a BRCA1 or BRCA2 gene mutation. It draws on ethnographic research conducted by between April-June 2016 in a large tertiary London hospital. Participant observation was conducted across two sites. For the first two weeks participant observation was conducted in the traditional genetic testing setting in two separate clinics. From thereon, participant observation was conducted in the clinical encounters of treating patients in the ovarian cancer clinic. In addition, face-to-face interviews were conducted with medical oncologists who worked in the clinic. Contributing to the fields of cancer genetics, personalised medicine and medical material culture studies in medical anthropology the paper seeks to further discussions about the interactions and relationships unfolding between medical objects and subjects across the landscape of cancer care. It highlights the importance of clinic-based ethnography to examine the complexities of identities and technologies as they intersect with the themes of suffering and hope in new and contradictory ways for BRCA-positive patients with late-stage disease. The paper argues that a BRCA mutation is not only central to the political economy of hope but takes on a more materialist nature as it becomes an embodied practice that moves in and beyond the clinic.

Assessing optimism and pessimism about genomic medicine: Development of a genomic orientation scale.

Efforts to characterize stakeholder attitudes about the implementation of genomic medicine would benefit from a validated instrument for measuring public views of the potential benefits and harms of genomic technologies, which would facilitate comparison across populations and clinical settings. We sought to develop a scale to evaluate attitudes about the future of genomic medicine. We developed a 21-item scale that examined the likelihood of various outcomes of genomic medicine. The scale was administered to participants in a genomic sequencing study. Exploratory factor analysis was conducted and bivariate correlations were calculated. The genomic orientation (GO) scale was completed by 2895 participants. A two-factor structure was identified, corresponding to an optimism subscale (16 items, α = 0.89) and a pessimism subscale (5 items, α = 0.63). Genomic optimism was positively associated with a perceived value of genetic test results, higher health literacy, and decreased decisional conflict about participation in a genomic research study. Genomic pessimism was associated with concerns about genetic testing, lower health literacy, and increased decisional conflict about the decision to participate in the study. The GO scale is a promising tool for measuring both positive and negative views regarding the future of genomic medicine and deserves further validation.

Self-management skills and behaviors, self-efficacy, and quality of life in people with epilepsy from underserved populations.

PURPOSE: People with epilepsy (PWE) from underserved populations face significant barriers to epilepsy management and therefore may lack knowledge about epilepsy and self-management (SM) of epilepsy. This paper evaluates SM practices, self-efficacy, outcome expectancy, quality of life, and personal impact of epilepsy in PWE from underserved populations as compared with all PWE. METHODS: Recruitment for the Managing Epilepsy Well (MEW) Network PAUSE to Learn Your Epilepsy study occurred from October 2015 to March 2019. Participants were assessed at baseline; after SM education intervention; and 6-, 9-, and 15-month postbaseline assessment. Baseline data from 112 PWE were analyzed for this report. RESULTS: Study population was diverse: 63% were women, 47.3% were non-Hispanic black, 24.1% were Hispanic, and 57.4% had public healthcare coverage. Participants on average had epilepsy for 14 years, and 49.1% reported at least one seizure within the past month, but only 27% reported having used a seizure diary or calendar for seizure tracking. Self-management practices & behaviors were significantly lower among PWE from underserved populations than all PWE, though self-efficacy among PWE from underserved populations was significantly higher. CONCLUSION: This study identifies the unique epilepsy SM needs of PWE from underserved populations. We discuss the need for a personalized approach for developing SM skills and behaviors among these PWE.

Parents of a child with epilepsy: Views and expectations on receiving genetic results from Whole Genome Sequencing.

PURPOSE: The use of Next Generation Sequencing technologies (NGS), such as Whole Genome Sequencing (WGS), is expected to improve the often complex and protracted course of treatment of patients with epilepsy by providing an earlier and more accurate diagnosis. As part of the "Personalized medicine in the treatment of epilepsy" project, which aimed to determine whether WGS could be used as a valuable "diagnostic tool" in pharmacoresistant epilepsies, we examined parents' expectations, hopes, and concerns upon receiving results related to their child's epilepsy, comorbidities, resistance to medication, and genetic information on unrelated conditions, and how these results could impact their and their child's life. METHODS: Parents of 32 children participating in the genetic study completed either paper or online questionnaires. A descriptive analysis of responses and comments was conducted regarding parents' experience with their child's epilepsy, as well as their views on WGS, and expectations and concerns surrounding such test results. RESULTS: Most respondents had trouble explaining the medical causes of their child's epilepsy (n = 27), and a majority (n = 26) feared that their child may be treated unjustly because of their epilepsy, although some acknowledged that their child had never actually been treated unjustly (n = 13). A majority of respondents had also experienced feelings of guilt due to their child's epilepsy (n = 23), and some expected WGS results to have an impact on those feelings. The anticipation of benefits for their child was the parents' primary reason to get involved in a genomic research project, closely followed by altruism. A majority expressed strong intentions to receive as many WGS results as possible, considering that any could be beneficial for them and their child, even when mutations were not found. Respondents were divided as to how and when to tell their child that they might have newly discovered predispositions to develop another disease. In proportion, more parents expressed concerns about sharing unexpected results with their family members compared with sharing results linked to epilepsy, comorbidities, and pharmacoresistance. CONCLUSION: Our results reinforce the importance of having clear guidelines to help parents manage their expectations and better navigate the complexities of receiving and sharing WGS results. Despite the small size of our sample, we believe that our results are meaningful to clinical practice.

Trial of personalised care after treatment-Prostate cancer: A randomised feasibility trial of a nurse-led psycho-educational intervention.

OBJECTIVE: The present parallel randomised control trial evaluated the feasibility of a nurse-led psycho-educational intervention aimed at improving the self-management of prostate cancer survivors. METHODS: We identified 305 eligible patients from a district general hospital, diagnosed 9-48 months previously, who completed radical treatment, or were monitored clinically (ineligible for treatment). Ninety-five patients were recruited by blinded selection and randomised to Intervention (N = 48) and Control (N = 47) groups. Participant allocation was revealed to patients and researchers after recruitment was completed. For 36 weeks, participants received augmented usual care (Control) or augmented usual care and additional nurse support (Intervention) provided in two community hospitals and a university clinic, or by telephone. RESULTS: Data from 91 participants (Intervention, N = 45; Control, N = 46) were analysed. All feasibility metrics met predefined targets: recruitment rate (31.15%; 95% CI: 25.95%-36.35%), attrition rate (9.47%; 95% CI: 3.58%-15.36%) and outcome measures completion rates (77%-92%). Forty-five patients received the intervention, with no adverse events. The Extended Prostate Cancer Index Composite can inform the minimum sample size for a future effectiveness trial. The net intervention cost was £317 per patient. CONCLUSIONS: The results supported the feasibility and acceptability of the intervention, suggesting that it should be evaluated in a fully powered trial to assess its effectiveness and cost-effectiveness.

Knowledge regarding and patterns of genetic testing in patients newly diagnosed with breast cancer participating in the iCanDecide trial.

BACKGROUND: The current study reports rates of knowledge regarding the probability of a BRCA1 and/or S pathogenic variant and genetic testing in patients with breast cancer, collected as part of a randomized controlled trial of a tailored, comprehensive, and interactive decision tool (iCanDecide). METHODS: A total of 537 patients newly diagnosed with early-stage breast cancer were enrolled at the time of their first visit in 22 surgical practices, and were surveyed 5 weeks (496 patients; Response Rate [RR], 92%) after enrollment after treatment decision making. Primary outcomes included knowledge regarding the probability of carrying a BRCA1 and/or BRCA2 pathogenic variant and genetic testing after diagnosis. RESULTS: Overall knowledge regarding the probability of having a BRCA1 and/or BRCA2 pathogenic variant was low (29.8%). Significantly more patients in the intervention group compared with the control group had knowledge regarding the probability of a BRCA1 and/or BRCA2 pathogenic variant (35.8% vs 24.4%; P <.006). In multivariable logistic regression, the intervention arm remained significantly associated with knowledge regarding the probability of having a BRCA1 and/or BRCA2 pathogenic variant (odds ratio, 1.79; 95% confidence interval, 1.18-2.70). CONCLUSIONS: The results of the current study suggest that although knowledge concerning the probability of having a BRCA1 and/or BRCA2 pathogenic variant remains low in this patient population, the interactive decision tool improved rates compared with a static Web site. As interest in genetic testing continues to rise, so will the need to integrate tools into the treatment decision process to improve informed decision making.

Revisiting Expectations in an Era of Precision Oncology.

As we enter an era of precision medicine and targeted therapies in the treatment of metastatic cancer, we face new challenges for patients and providers alike as we establish clear guidelines, regulations, and strategies for implementation. At the crux of this challenge is the fact that patients with advanced cancer may have disproportionate expectations of personal benefit when participating in clinical trials designed to generate generalizable knowledge. Patient and physician goals of treatment may not align, and reconciliation of their disparate perceptions must be addressed. However, it is particularly challenging to manage a patient's expectations when the goal of precision medicine-personalized response-exacerbates our inability to predict outcomes for any individual patient. The precision medicine informed consent process must therefore directly address this issue. We are challenged to honestly, clearly, and compassionately engage a patient population in an informed consent process that is responsive to their vulnerability, as well as ever-evolving indications and evidence. This era requires a continual reassessment of expectations and goals from both sides of the bed.

Representing a "revolution": how the popular press has portrayed personalized medicine.

PURPOSE: This study investigated the portrayal of "personalized" and "precision" medicine (PM) in North American news over the past decade. Content analysis of print and online news was conducted to determine how PM has been defined and to identify the frames used to discuss PM, including associated topics, benefits, and concerns. METHODS: A data set was built using the FACTIVA database, searching for popular North American publications with the terms "personalized (personalised) medicine" and/or "precision medicine" from 1 January 2005 to 15 March 2016. The final set of publications totaled 774. RESULTS: PM is almost exclusively defined as related to genetics and is often part of a story related to cancer. The PM story is overwhelmingly one of highlighting (potential) benefits and optimism, especially in shorter publications, and ones where PM is not the main focus. This promotional PM discourse has remained fairly consistent over the past decade. CONCLUSION: The numerous concerns associated with PM have received little attention over the past decade, especially in articles more likely to be encountered by a more general audience. This promotion of PM serves as an example of the science hyping that takes place in science reportage and may have implications for consumers, public expectations, and related health policy.

Predictive analytics in mental health: applications, guidelines, challenges and perspectives.

The emerging field of 'predictive analytics in mental health' has recently generated tremendous interest with the bold promise to revolutionize clinical practice in psychiatry paralleling similar developments in personalized and precision medicine. Here, we provide an overview of the key questions and challenges in the field, aiming to (1) propose general guidelines for predictive analytics projects in psychiatry, (2) provide a conceptual introduction to core aspects of predictive modeling technology, and (3) foster a broad and informed discussion involving all stakeholders including researchers, clinicians, patients, funding bodies and policymakers.

Pluripotent stem cells in neuropsychiatric disorders.

Neuropsychiatric disorders place an enormous medical burden on patients across all social and economic ranks. The current understanding of the molecular and cellular causes of neuropsychiatric disease remains limited, which leads to a lack of targeted therapies. Human-induced pluripotent stem cell (iPSC) technology offers a novel platform for modeling the genetic contribution to mental disorders and yields access to patient-specific cells for drug discovery and personalized medicine. Here, we review recent progress in using iPSC technology to model and potentially treat neuropsychiatric disorders by focusing on the most prevalent conditions in psychiatry, including depression, anxiety disorders, bipolar disorder and schizophrenia.

Personalized Boosters After a Computerized Intervention Targeting College Drinking: A Randomized Controlled Trial.

BACKGROUND: Problematic drinking among emerging adult college students is extensive. Computer-delivered interventions (CDIs) have strong appeal because they can be quickly delivered to large numbers of students. Although they are efficacious in the short term, CDIs are not as efficacious as in-person interventions longer term. This study examined the utility of emailed boosters containing personalized feedback after a CDI to enhance and extend reductions among emerging adult college drinkers. Sex and age were explored as potential moderators. METHODS: Participants were 537 college students (67.4% female) aged 18 to 24 years (M age = 19.65, SD = 1.67) who consumed at least 1 alcoholic drink in the past 2 weeks. They were randomly assigned to CDI-only, CDI + booster email, or an assessment-only control condition, and were assessed up to 9 months postintervention. A booster email with personalized feedback was sent to the CDI + booster email group 2 weeks after completion of the CDI. RESULTS: Moderation findings for age revealed that the booster may be an effective means to strengthen and extend intervention effects for emerging adults who are of legal drinking age. However, effects were negligible for underage drinkers. Although the booster effect for the overall sample demonstrated a trend in the expected direction, it failed to reach significance. Booster effects were not significantly moderated by sex. Intervention effects were not moderated by either age or sex. CONCLUSIONS: The present investigation contributes to a limited body of research on boosters to augment main intervention effects in college drinkers. Our study demonstrated that a brief CDI plus a simple email booster with personalized feedback resulted in significant reductions in drinking outcomes for emerging adults of legal drinking age. Efforts to further develop and refine intervention booster strategies represent a promising future direction to minimize harmful drinking among college students.

Mediators and Moderators of a Personalized Feedback Alcohol Intervention for Nonstudent Emerging Adult Drinkers.

BACKGROUND: The main objective of this study was to test proposed mediators and moderators of a personalized feedback alcohol intervention (PFI) on alcohol use. Data for the current investigation came from an earlier randomized controlled trial of a PFI targeted for nonstudent heavy drinkers between 18 and 25 years. METHODS: Participants were 164 (65.9% men) drinkers recruited from the community. They were randomly assigned to either a single-session PFI or an assessment-only (AO) control group. Follow-up assessments at 1 and 3 months were included for analysis. RESULTS: Perceived drinking norms mediated the intervention effect on quantity, frequency, and peak drinking; 2 dimensions of protective behavioral strategies (PBS) mediated the intervention effect on peak drinking; and drinking to cope motives did not mediate any drinking outcomes. Of the moderating factors examined (i.e., norms, PBS, drink to cope motives, age, gender), only PBS related to serious harm reduction moderated intervention impact. Specifically, for those high in serious harm reduction PBS at baseline, postintervention reductions in drinking were stronger for the PFI group compared to AO. CONCLUSIONS: Overall, findings highlight the importance of correcting misperceived drinking norms and addressing the use of specific PBS in brief interventions. The knowledge gained from this study represents an important step toward minimizing drinking-related harms that are disproportionately experienced by those with lower educational attainment.

Implementing personalized medicine in diabetic kidney disease: Stakeholders' perspectives.

The promise of personalized medicine to deliver "the right treatments at the right time to the right person" is the next frontier in healthcare. However, to implement personalized medicine in chronic diseases such as diabetes mellitus and diabetic kidney disease (DKD), a number of different aspects need to be taken into account. Better risk stratification and more precise options for treatment need to be developed and included in clinical practice guidelines. A patient's unique psychological, social and environmental situation also drive disease progression and outcomes. Appraising the cost effectiveness of precision medicines is necessary, not just as the cost of new therapies, but also the cost of diagnosis with novel methodologies and averted complications. As the prevalence of DKD grows worldwide to epidemic proportions, challenges such as global disparities in resources, access to healthcare and prevalence need to be addressed. This review considers these issues to achieve the short and longer-term goals of implementing personalized medicine in clinical practice.

Leveraging Genomic Data in Smoking Cessation Trials in the Era of Precision Medicine: Why and How.

Implications: This article outlines a framework for the consistent integration of biological data/samples into smoking cessation pharmacotherapy trials, aligned with the objectives of the recently unveiled Precision Medicine Initiative. Our goal is to encourage and provide support for treatment researchers to consider biosample collection and genotyping their existing samples as well as integrating genetic analyses into their study design in order to realize precision medicine in treatment of nicotine dependence.