Family secrets: Experiences and outcomes of participating in direct-to-consumer genetic relative-finder services.

In recent decades, genetic genealogy has become popular as a result of direct-to-consumer (DTC) genetic testing. Some DTC genetic testing companies offer genetic relative-finder (GRF) services that compare the DNA of consenting participants to identify genetic relatives among them and provide each participant a list of their relative matches. We surveyed a convenience sample of GRF service participants to understand the prevalence of discoveries and associated experiences. Almost half (46%) of the 23,196 respondents had participated in GRF services only for non-specific reasons that included interest in building family trees and general curiosity. However, most (82%) also learned the identity of at least one genetic relative. Separately, most respondents (61%) reported learning something new about themselves or their relatives, including potentially disruptive information such as that a person they believed to be their biological parent is in fact not or that they have a sibling they had not known about. Respondents generally reported that discovering this new information had a neutral or positive impact on their lives, and most had low regret regarding their decision to participate in GRF services. Yet some reported making life changes as a result of their discoveries. Compared to respondents making other types of discoveries, those who learned that they were donor conceived reported the highest decisional regret and represented the largest proportion reporting net-negative consequences for themselves. Our findings indicate that discoveries from GRF services may be common and that the consequences for individuals, while generally positive, can be far-reaching and complex.

Satisfaction with Mode of Delivery of Genomic Sequencing Results in a Diverse National Sample of Research Participants through the Clinical Sequencing Evidence-Generating Research Consortium.

PURPOSE: Research that includes diverse patient populations is necessary to optimize implementation of telehealth. METHODS: As part of a Clinical Sequencing Evidence-Generating Research Consortium cross-site study, we assessed satisfaction with mode of return of results (RoR) delivery across a diverse sample of participants receiving genetic testing results in-person (IP) versus telemedicine (TM) RESULTS: Ninety-eight percent of participants were satisfied with their mode of results delivery. Participants receiving results by TM were more likely to report a preference for receiving results in a different way and challenges with providers noticing difficulties with understanding. Greater than 90% reported satisfaction across all items measuring support and interaction during sessions. Participants self-reporting Hispanic/Latino or Black/African American race/ethnicity compared to White/European American, fewer years of education, and having lower health literacy were more likely to report challenges with understanding the information or asking questions. Participants who were White/European American, had more years of education, and higher health literacy reported higher communication scores reflecting more positive evaluations of the communication experience. CONCLUSION: TM is an acceptable mode of RoR delivery across diverse settings and populations. Research optimizing approaches for underrepresented populations, populations with lower levels of education and health literacy, and multilingual populations is necessary.

Genomic sequencing research in pediatric cancer care: Decision making, attitudes, and perceived utility among adolescents and young adults and their parents.

PURPOSE: Professional guidelines recommend engaging adolescents and young adults (AYAs) in medical decision making (DM), including whether to undergo genomic sequencing (GS). We explored DM around GS and attitudes after return of GS results among a diverse group of AYAs with cancer and their parents. METHODS: We surveyed AYAs with cancer (n = 75) and their parents (n = 52) 6 months after receiving GS results through the Texas KidsCanSeq study. We analyzed AYAs' DM role in GS research enrollment and their satisfaction with that role. We compared AYAs' and parents' self-reported understanding of, attitudes toward, and perceived utility of the AYA's GS results. RESULTS: Most AYAs reported equally sharing DM with their parents (55%) or leading DM (36%) about GS research. Compared with their cancer care DM role, 56% of AYAs reported the same level of involvement in GS research DM, whereas 32% were more involved, and 13% were less involved (P = .011). AYAs were satisfied (99%) with their DM role regarding GS study participation. AYAs and parents had similar self-reported understanding of, attitudes toward, and perceived utility of the GS results. CONCLUSION: Our results support engaging AYAs in DM about GS research and provide insights into AYAs' DM preferences and positive attitudes toward GS.

Families' experiences accessing care after genomic sequencing in the pediatric cancer context: "It's just been a big juggle".

Access to genomic sequencing (GS) and resulting recommendations have not been well described in pediatric oncology. GS results may provide a cancer predisposition syndrome (CPS) diagnosis that warrants screening and specialist visits beyond cancer treatment, including testing or surveillance for family members. The Texas KidsCanSeq (KCS) Study evaluated implementation of GS in a diverse pediatric oncology population. We conducted semi-structured interviews (n = 20) to explore experiences of KCS patients' families around learning about a CPS diagnosis and following up on recommended care. We used qualitative content analysis to develop themes and subthemes across families' descriptions of their experiences accessing care and to understand which factors presented barriers and/or facilitators. We found participants had difficulty differentiating which follow-up care recommendations were made for their child's current cancer treatment versus the CPS. In families' access to follow-up care for CPS, organizational factors were crucial: travel time and distance were common hardships, while coordination of care to streamline multiple appointments with different providers helped facilitate CPS care. Financial factors also impacted families' access to CPS-related follow-up care: having financial assistance and insurance were facilitators for families, while costs and lack of insurance posed as barriers for patients who lost coverage during transitions from pediatric to adult care, and for adult family members who had no coverage. Factors related to beliefs and perceptions, specifically perceiving the risk as less salient to them and feeling overwhelmed with the patient's cancer care, presented barriers to follow-up care primarily for family members. Regarding social factors, competing life priorities made it difficult for families to access follow-up care, though having community support alleviated these barriers. We suggest interventions to improve coordination of cancer treatment and CPS-related care and adherence to surveillance protocols for families as children age, such as care navigators and integrating longitudinal genetic counseling into hereditary cancer centers.

Conducting clinical genomics research during the COVID-19 pandemic: Lessons learned from the CSER consortium experience.

Clinical research studies have navigated many changes throughout the COVID-19 pandemic. We sought to describe the pandemic's impact on research operations in the context of a clinical genomics research consortium that aimed to enroll a majority of participants from underrepresented populations. We interviewed (July to November 2020) and surveyed (May to August 2021) representatives of six projects in the Clinical Sequencing Evidence-Generating Research (CSER) consortium, which studies the implementation of genome sequencing in the clinical care of patients from populations that are underrepresented in genomics research or are medically underserved. Questions focused on COVID's impact on participant recruitment, enrollment, and engagement, and the transition to teleresearch. Responses were combined and thematically analyzed. Projects described factors at the project, institutional, and community levels that affected their experiences. Project factors included the project's progress at the pandemic's onset, the urgency of in-person clinical care for the disease being studied, and the degree to which teleresearch procedures were already incorporated. Institutional and community factors included institutional guidance for research and clinical care and the burden of COVID on the local community. Overall, being responsive to community experiences and values was essential to how CSER navigated evolving challenges during the COVID-19 pandemic.

Effects of participation in a U.S. trial of newborn genomic sequencing on parents at risk for depression.

Much emphasis has been placed on participant's psychological safety within genomic research studies; however, few studies have addressed parental psychological health effects associated with their child's participation in genomic studies, particularly when parents meet the threshold for clinical concern for depression. We aimed to determine if parents' depressive symptoms were associated with their child's participation in a randomized-controlled trial of newborn exome sequencing. Parents completed the Edinburgh Postnatal Depression Scale (EPDS) at baseline, immediately post-disclosure, and 3 months post-disclosure. Mothers and fathers scoring at or above thresholds for clinical concern on the EPDS, 12 and 10, respectively, indicating possible Major Depressive Disorder with Peripartum Onset, were contacted by study staff for mental health screening. Parental concerns identified in follow-up conversations were coded for themes. Forty-five parents had EPDS scores above the clinical threshold at baseline, which decreased by an average of 2.9 points immediately post-disclosure and another 1.1 points 3 months post-disclosure (both p ≤ .014). For 28 parents, EPDS scores were below the threshold for clinical concern at baseline, increased by an average of 4.7 points into the elevated range immediately post-disclosure, and decreased by 3.8 points at 3 months post-disclosure (both p < .001). Nine parents scored above thresholds only at 3 months post-disclosure after increasing an average of 5.7 points from immediately post-disclosure (p < .001). Of the 82 parents who scored above the threshold at any time point, 43 (52.4%) were reached and 30 (69.7%) of these 43 parents attributed their elevated scores to parenting stress, balancing work and family responsibilities, and/or child health concerns. Only three parents (7.0%) raised concerns about their participation in the trial, particularly their randomization to the control arm. Elevated scores on the EPDS were typically transient and parents attributed their symptomatology to life stressors in the postpartum period rather than participation in a trial of newborn exome sequencing.

Should police have access to genetic genealogy databases? Capturing the Golden State Killer and other criminals using a controversial new forensic technique.

On April 24, 2018, a suspect in California's notorious Golden State Killer cases was arrested after decades of eluding the police. Using a novel forensic approach, investigators identified the suspect by first identifying his relatives using a free, online genetic database populated by individuals researching their family trees. In the wake of the case, media outlets reported privacy concerns with police access to personal genetic data generated by or shared with genealogy services. Recent data from 1,587 survey respondents, however, provide preliminary reason to question whether such concerns have been overstated. Still, limitations on police access to genetic genealogy databases in particular may be desirable for reasons other than current public demand for them.

Educating military primary health-care providers in genomic medicine: lessons learned from the MilSeq Project.

PURPOSE: With few trained genetics professionals, the Military Health System is ill-equipped to manage the rapid expansion of genomic medicine. The MilSeq Project introduces an alternative service delivery model (ASDM) in which primary health-care providers (HCPs) provide post-test counseling (PTC) to healthy Airmen who have undergone exome sequencing. We describe HCP performance after a prerequisite educational intervention (EI). METHODS: After a brief EI and pre-/posteducation surveys, HCPs were eligible to provide PTC with a genetic counselor available for consult. PTC was recorded, transcribed, and reviewed. Opportunities for improvement were organized into four error adjustment categories: (1) knowledge limitation, (2) minor, (3) moderate, and (4) critical. Thematic analysis was also performed. RESULTS: Pre-/posteducation survey responses revealed statistically significant improvements in all domains. Minor error adjustments were most represented (n = 93), followed by knowledge limitation (n = 39) and moderate (n = 19). No critical errors were identified, and 17 transcripts required no adjustment. Thematic analysis revealed four themes that would benefit from more focused education: (1) family-centered care, (2) conveying risk, (3) disease knowledge, and (4) assay knowledge. CONCLUSION: HCPs demonstrated competence in basic PTC after a brief EI. This ASDM may be a viable interim response to the shortage of genetics professionals in some systems.

Responsibility, culpability, and parental views on genomic testing for seriously ill children.

PURPOSE: We describe parental perceptions of and experiences with genomic sequencing (GS) in the care of seriously ill children. Understanding parents' perspectives is vital for clinicians caring for children, given the uptake of genomic technologies into clinical practice. METHODS: Longitudinal, semistructured interviews were conducted with parents of pediatric cancer patients who underwent exome sequencing (ES) as a part of the BASIC3 study. Interviews were conducted at baseline, one to eight months after results disclosure, and approximately one year after disclosure. Using thematic qualitative analysis, parent interviews were coded with both inductive and deductive approaches. RESULTS: Before receiving genomic information, parents indicated that they saw ES as something responsible parents would agree to if their child had cancer. Some parents talked about the possibility of sequencing affecting feelings of culpability for their child's cancer, worrying that they passed on a cancer-causing gene or made parenting decisions that caused the disease. However, after receiving their child's ES results many reported feeling relieved of guilt and worry, and felt they had fulfilled parental duties by agreeing to ES for their child. CONCLUSION: These results reveal a layer of meaning that parents associate with GS that may inform clinicians' approach to care.

Parental interest in genomic sequencing of newborns: enrollment experience from the BabySeq Project.

PURPOSE: Newborn genomic sequencing (nGS) has great potential to improve pediatric care. Parental interest and concerns about genomics are relatively unexplored. Understanding why parents decline research consent for nGS may reveal implementation barriers. METHODS: We evaluated parental interest in a randomized trial of nGS in well-baby and intensive care unit nursery settings. Interested families attended an informational enrollment session (ES) with a genetic counselor prior to consenting. Reason(s) for declining participation and sociodemographic associations were analyzed. RESULTS: Of 3860 eligible approached families, 10% attended ES, 67% of whom enrolled. Of 1760 families queried for decline reasons, 58% were uninterested in research. Among 499 families considering research, principal reasons for decline prior to ES included burdensome study logistics (48%), feeling overwhelmed postpartum (17%), and lack of interest/discomfort with genetic testing (17%). Decliners after ES more often cited concerns about privacy/insurability (41%) and uncertain/unfavorable results (23%). CONCLUSION: Low interest in research and study logistics were major initial barriers to postpartum enrollment and are likely generic to many postpartum research efforts. Concerns over privacy and result implications were most commonly cited in decliners after ES. Understanding parental concerns around research nGS may inform future integration of nGS into newborn screening, predictive testing, and pediatric diagnostics.

Psychological outcomes related to exome and genome sequencing result disclosure: a meta-analysis of seven Clinical Sequencing Exploratory Research (CSER) Consortium studies.

PURPOSE: As exome and genome sequencing (ES/GS) enters the clinic, there is an urgent need to understand the psychological effects of test result disclosure. Through a Clinical Sequencing Exploratory Research (CSER), phase 1 (CSER1) Consortium collaboration, we evaluated participants' psychological outcomes across multiple clinical settings. METHODS: We conducted a random effects meta-analysis of state anxiety (Hospital Anxiety and Depression Scale [HADS]/Generalized Anxiety Disorder 7-item), depressive symptoms (HADS/Personal Health Questionnaire 9-item), and multidimensional impact (i.e., test-related distress, uncertainty and positive impact: modified Multidimensional Impact of Cancer Risk Assessment/Feelings About Genomic Testing Results scale). RESULTS: Anxiety and depression did not increase significantly following test result disclosure. Meta-analyses examining mean differences from pre- to postdisclosure revealed an overall trend for a decrease in participants' anxiety. We observed low levels of test-related distress and perceptions of uncertainty in some populations (e.g., pediatric patients) and a wide range of positive responses. CONCLUSION: Our findings across multiple clinical settings suggest no clinically significant psychological harms from the return of ES/GS results. Some populations may experience low levels of test-related distress or greater positive psychological effects. Future research should further investigate the reasons for test-related psychological response variation.

Patient understanding of, satisfaction with, and perceived utility of whole-genome sequencing: findings from the MedSeq Project.

PURPOSE: To examine patients' experiences with clinical use of whole-genome sequencing (WGS). METHODS: A randomized trial compared primary care and cardiology patients receiving WGS and family health history (FH) information or FH information alone. 202 patients were surveyed before (BL) and up to 6 months after disclosure of results (6M). RESULTS: Patients (mean age = 55 years; 50% female; 81% college graduates) reported low levels of decisional regret (mean: 7.1/100) and high satisfaction with physicians' disclosure of results (median: 29/30). Compared with the FH-only arm, patients receiving WGS results were more likely to report learning accurate disease risk information (odds ratio = 7.45) and findings influential for medical treatment (odds ratio = 2.39). Sessions where WGS results were disclosed took longer (30 vs. 15 minutes), particularly for primary care patients. Patients' expected utility of sequencing at BL was higher than perceived utility at 6M in several domains, including impacting medical decision making (87% vs. 54%) and influencing medication choice (73% vs. 32%). CONCLUSION: Patients were satisfied with their physicians' communication of WGS results and perceived them as medically useful. Discrepancies in expected versus perceived utility of WGS results suggest a need to temper patients' expectations about its potential benefits.

Short-term costs of integrating whole-genome sequencing into primary care and cardiology settings: a pilot randomized trial.

PURPOSE: Great uncertainty exists about the costs associated with whole-genome sequencing (WGS). METHODS: One hundred cardiology patients with cardiomyopathy diagnoses and 100 ostensibly healthy primary care patients were randomized to receive a family-history report alone or with a WGS report. Cardiology patients also reviewed prior genetic test results. WGS costs were estimated by tracking resource use and staff time. Downstream costs were estimated by identifying services in administrative data, medical records, and patient surveys for 6 months. RESULTS: The incremental cost per patient of WGS testing was $5,098 in cardiology settings and $5,073 in primary care settings compared with family history alone. Mean 6-month downstream costs did not differ statistically between the control and WGS arms in either setting (cardiology: difference = -$1,560, 95% confidence interval -$7,558 to $3,866, p = 0.36; primary care: difference = $681, 95% confidence interval -$884 to $2,171, p = 0.70). Scenario analyses showed the cost reduction of omitting or limiting the types of secondary findings was less than $69 and $182 per patient in cardiology and primary care, respectively. CONCLUSION: Short-term costs of WGS were driven by the costs of sequencing and interpretation rather than downstream health care. Disclosing additional types of secondary findings has a limited cost impact following disclosure.

Why Patients Decline Genomic Sequencing Studies: Experiences from the CSER Consortium.

Clinical and research settings are increasingly incorporating genomic sequencing (GS) technologies. Previous research has explored reasons for declining genetic testing and participation in genetic studies; however, there is a dearth of literature regarding why potential participants decline participation in GS research, and if any of these reasons are unique to GS. This knowledge is essential to promote informed decision-making and identify potential barriers to research participation and clinical implementation. We aggregated data from seven sites across the National Institutes of Health's Clinical Sequencing Exploratory Research (CSER) consortium on each project's procedures for recruitment, and rates of and reasons for decline. Data were analyzed using descriptive statistics. The decline rate for enrollment at the seven CSER sites ranged from 12 to 64% (median 28%) and varied based on age and disease status. Projects differed in their protocols for approaching potential participants and obtaining informed consent. Reasons for declining GS research were reported for 1088 potential participants. Commonly cited reasons were similar to those reported for clinical single gene testing and non-GS genetic research. The most frequently cited reason for decline was study logistics (35%); thus, addressing logistical barriers to enrollment may positively impact GS study recruitment. Privacy and discrimination concerns were cited by 13% of decliners, highlighting the need for researchers and providers to focus educational efforts in this area. The potential psychological burden of pursuing and receiving results from GS and not wanting to receive secondary findings, a concern specific to GS, have been cited as concerns in the literature. A minority of potential participants cited psychological impact (8%) or not wanting to receive secondary findings (2%) as reasons for decline, suggesting that these concerns were not major barriers to participation in these GS studies. Further research is necessary to explore the impact, if any, of different participant groups or study protocols on rates of decline for GS studies. Future studies exploring GS implementation should consider using standardized collection methods to examine reasons for decline in larger populations and more diverse healthcare settings.

The Impact of Whole-Genome Sequencing on the Primary Care and Outcomes of Healthy Adult Patients: A Pilot Randomized Trial.

Background: Whole-genome sequencing (WGS) in asymptomatic adults might prevent disease but increase health care use without clinical value. Objective: To describe the effect on clinical care and outcomes of adding WGS to standardized family history assessment in primary care. Design: Pilot randomized trial. (ClinicalTrials.gov: NCT01736566). Setting: Academic primary care practices. Participants: 9 primary care physicians (PCPs) and 100 generally healthy patients recruited at ages 40 to 65 years. Intervention: Patients were randomly assigned to receive a family history report alone (FH group) or in combination with an interpreted WGS report (FH + WGS group), which included monogenic disease risk (MDR) results (associated with Mendelian disorders), carrier variants, pharmacogenomic associations, and polygenic risk estimates for cardiometabolic traits. Each patient met with his or her PCP to discuss the report. Measurements: Clinical outcomes and health care use through 6 months were obtained from medical records and audio-recorded discussions between PCPs and patients. Patients' health behavior changes were surveyed 6 months after receiving results. A panel of clinician-geneticists rated the appropriateness of how PCPs managed MDR results. Results: Mean age was 55 years; 58% of patients were female. Eleven FH + WGS patients (22% [95% CI, 12% to 36%]) had new MDR results. Only 2 (4% [CI, 0.01% to 15%]) had evidence of the phenotypes predicted by an MDR result (fundus albipunctatus due to RDH5 and variegate porphyria due to PPOX). Primary care physicians recommended new clinical actions for 16% (CI, 8% to 30%) of FH patients and 34% (CI, 22% to 49%) of FH + WGS patients. Thirty percent (CI, 17% to 45%) and 41% (CI, 27% to 56%) of FH and FH + WGS patients, respectively, reported making a health behavior change after 6 months. Geneticists rated PCP management of 8 MDR results (73% [CI, 39% to 99%]) as appropriate and 2 results (18% [CI, 3% to 52%]) as inappropriate. Limitation: Limited sample size and ancestral and socioeconomic diversity. Conclusion: Adding WGS to primary care reveals new molecular findings of uncertain clinical utility. Nongeneticist providers may be able to manage WGS results appropriately, but WGS may prompt additional clinical actions of unclear value. Primary Funding Source: National Institutes of Health.

IGG in the trenches: Results of an in-depth interview study on the practice, politics, and future of investigative genetic genealogy.

Investigative genetic genealogy (IGG) is a new technique for identifying criminal suspects and unidentified deceased and living persons that has sparked controversy. In a criminal case, the technique involves uploading genetic information left by a putative perpetrator at the crime scene to one or more direct-to-consumer genetic genealogy databases with the intention of identifying the perpetrator's genetic relatives and, eventually, locating the perpetrator on the family tree. In 2018, IGG helped to identify the Golden State Killer, and it has since been used in hundreds of investigations in the United States. Here, we report findings from in-depth interviews with 24 U.S.-based individuals involved in IGG that are relevant to the technique's current practice and predicted future. Key findings include: an emphasis on restricting IGG as a conceptual and technical matter to lead generation; the rapid growth of a private and largely self-regulating industry to support IGG; general recognition of three categories of cases associated with distinct practical, ethical, and policy questions, as well as varying degrees of controversy; and the significant influence of perceived public opinion on IGG practice. The experiences and perspectives of individuals in the IGG trenches related to these and other issues are potentially useful inputs to ongoing efforts to regulate the technique.

Public Perspectives on Investigative Genetic Genealogy: Findings from a National Focus Group Study.

BACKGROUND: Investigative genetic genealogy (IGG) is a technique that involves uploading genotypes developed from perpetrator DNA left at a crime scene, or DNA from unidentified remains, to public genetic genealogy databases to identify genetic relatives and, through the creation of a family tree, the individual who was the source of the DNA. As policymakers demonstrate interest in regulating IGG, it is important to understand public perspectives on IGG to determine whether proposed policies are aligned with public attitudes. METHODS: We conducted eight focus groups with members of the public (N = 72), sampled from four geographically diverse US regions, to explore general attitudes and perspectives regarding aspects of IGG practices, applications, and policies. Five major topics were explored in each focus group: when IGG should be used; who should perform IGG; how to approach consent for genetic database users; what systems of oversight should govern IGG practitioners; and whether to notify database users if their data are involved in law enforcement (LE) matching. RESULTS: Participants were supportive of IGG in most scenarios, especially for cold and violent cases. The favorable attitudes toward IGG were, however, tempered by distrust of law enforcement among some participants. All participants agreed that databases must inform users if IGG is allowed, but they did not agree on how individual database users should be allowed to opt out or whether to notify them if their data are involved in specific investigations. All participants agreed that IGG should be subject to some prescriptive guidelines, regulations, or accountability mechanisms. CONCLUSIONS: These findings suggest broad public support for IGG, and interest in developing systems of accountability for its practice. Our study provides useful insight for policy makers, genomic database stewards, law enforcement, and other stakeholders in IGG's practice, and suggests multiple directions for future research.

Research Participants' Perspectives on Precision Diagnostics for Alzheimer's Disease.

BACKGROUND: Understanding research participants' responses to learning Alzheimer's disease (AD) risk information is important to inform clinical implementation of precision diagnostics given rapid advances in disease modifying therapies. OBJECTIVE: We assessed participants' perspectives on the meaning of their amyloid positron emission tomography (PET) imaging results for their health, self-efficacy to understand their results, psychological impact of learning their results, experience receiving their results from the clinical team, and interest in genetic testing for AD risk. METHODS: We surveyed individuals who were being clinically evaluated for AD and received PET imaging six weeks after the return of results. We analyzed responses to close-ended survey items by PET result using Fisher's exact test and qualitatively coded open-ended responses. RESULTS: A total of 88 participants completed surveys, most of whom had mild cognitive impairment due to AD (38.6%), AD (28.4%), or were cognitively unimpaired (21.6%). Participants subjectively understood their results (25.3% strongly agreed, 41.8% agreed), which could help them plan (16.5% strongly agreed, 49.4% agreed). Participants with a negative PET result (n = 25) reported feelings of relief (Fisher's exact p < 0.001) and happiness (p < 0.001) more frequently than those with a positive result. Most participants felt that they were treated respectfully and were comfortable voicing concerns during the disclosure process. Genetic testing was anticipated to be useful for medical care decisions (48.2%) and to inform family members about AD risk (42.9%). CONCLUSIONS: Participants had high subjective understanding and self-efficacy around their PET results and did not experience negative psychological effects. Interest in genetic testing was high.

Public mental health during and after the SARS-CoV-2 pandemic: Opportunities for intervention via emotional self-efficacy and resilience.

Importance: During the pandemic, the number of United States adults reporting clinically significant symptoms of anxiety and depression sky-rocketed, up from 11% in 2020 to more than 40% in 2021. Our current mental healthcare system cannot adequately accommodate the current crisis; it is therefore important to identify opportunities for public mental health interventions. Objective: Assess whether modifiable emotional factors may offer a point of intervention for the mental health crisis. Design setting and participants: From January 13 to 15, 2022, adults living in the United States were recruited via Amazon Mechanical Turk to complete an anonymous survey. Main outcomes and measures: Linear regressions tested whether the primary outcomes during the SARS-CoV-2 pandemic (depressive and anxiety symptoms, burnout) were associated with hypothesized modifiable risk factors (loneliness and need for closure) and hypothesized modifiable protective factors (the ability to perceive emotions and connect with others emotionally; emotion-regulation efficacy; and resilience, or the ability to "bounce back" after negative events). Results: The sample included 1,323 adults (mean [SD] age 41.42 [12.52] years; 636 women [48%]), almost half of whom reported clinically significant depressive (29%) and/or anxiety (15%) symptoms. Approximately 90% of participants indicated feeling burned out at least once a year and nearly half of participants (45%) felt burned out once a week or more. In separate analyses, depressive symptoms (Model A), anxiety symptoms (Model B), and burnout (Model C) were statistically significantly associated with loneliness (ßModel A, 0.38; 95% CI, 0.33-0.43; ßModel B, 0.30; 95% CI, 0.26-0.36; ßModel C, 0.34; 95% CI, 0.28-0.41), need for closure (ßModel A, 0.09; 95% CI, 1.03-1.06; ßModel B, 0.13; 95% CI, 0.97-0.17; ßModel C, 0.11; 95% CI, 0.07-0.16), recent stressful life events (ßModel A, 0.14; 95% CI, 0.10-0.17; ßModel B, 0.14; 95% CI, 0.11-0.18; ßModel C, 0.10; 95% CI, 0.06-0.15), and resilience (ßModel A, -0.10; 95% CI, -0.15 to -0.05; ßModel B, -0.18; 95% CI, -0.23 to -0.13; ßModel C, -0.11; 95% CI, -0.17 to -0.05). In addition, depressive and anxiety symptoms were associated with emotional self-efficacy (ßModel A, -0.17; 95% CI, -0.22 to -0.12; ßModel B, -0.11; 95% CI, -0.17 to -0.06), and beliefs about the malleability of emotions (ßModel A, -0.08; 95% CI, -0.12 to -0.03; ßModel B, -0.09; 95% CI, -0.13 to -0.04). Associations between loneliness and symptoms were weaker among those with more emotional self-efficacy, more endorsement of emotion malleability beliefs, and greater resilience, in separate models. Analyses controlled for recent stressful life events, optimism, and social desirability. Conclusion and relevance: Public mental health interventions that teach resilience in response to negative events, emotional self-efficacy, and emotion-regulation efficacy may protect against the development of depressive symptoms, anxiety, and burnout, particularly in the context of a collective trauma. Emotional self-efficacy and regulation efficacy may mitigate the association between loneliness and mental health, but loneliness prevention research is also needed to address the current mental health crisis.

Policy options to facilitate cancer genomic variant data sharing: outcomes of a modified policy Delphi.

Sharing cancer gene variant and relevant clinical data could accelerate progress in cancer genomics. However, data sharing is currently impeded by issues related to financial sustainability, equity, incentives, privacy and security, and data quality. Evidence-based policy options to facilitate data sharing in these domains, and ultimately improve interpretation of cancer-associated genomic variants, are therefore needed. We conducted a modified policy Delphi with expert stakeholders that involved generating, evaluating, and ranking potential policy options to address these issues, with a focus on the US context. We found policy options in the financial sustainability domain were highly ranked, particularly stable funding for trusted entities. However, some Delphi panelists noted that the culture of public research funding has favored short-term grants. Panelists favored policy options focused on action by funders, which had the highest overall total scores that combined effectiveness and feasibility ratings and priority ranking within domains. Panelists also endorsed some policy options connected to actors such as journals, but they were more skeptical of policy options connected to legislative actors and data resources. These findings are critical inputs for policy makers as they consider policies to enable sharing of cancer gene variant data to improve health.