Conceptualization of utility in translational clinical genomics research.

Prior to integration into clinical care, a novel medical innovation is typically assessed in terms of its balance of benefits and risks, often referred to as utility. Members of multidisciplinary research teams may conceptualize and assess utility in different ways, which has implications within the translational genomics community and for the evidence base upon which clinical guidelines groups and healthcare payers make decisions. Ambiguity in the conceptualization of utility in translational genomics research can lead to communication challenges within research teams and to study designs that do not meet stakeholder needs. We seek to address the ambiguity challenge by describing the conceptual understanding of utility and use of the term by scholars in the fields of philosophy, medicine, and the social sciences of decision psychology and health economics. We illustrate applications of each field's orientation to translational genomics research by using examples from the Clinical Sequencing Evidence-Generating Research (CSER) consortium, and we provide recommendations for increasing clarity and cohesion in future research. Given that different understandings of utility will align to a greater or lesser degree with important stakeholders' views, more precise use of the term can help researchers to better integrate multidisciplinary investigations and communicate with stakeholders.

Group-based medical mistrust in genomic medicine: Associations with patient and provider perceptions of a specialty clinical encounter.

OBJECTIVE: Investigating associations between group-based medical mistrust (GBMM) and perceptions of patient-provider encounters can identify one mechanism through which GBMM may influence health outcomes and serve as a barrier to equitable healthcare. The present study investigated associations between GBMM reported by caregivers of children with a possibly genetic condition and caregivers' and providers' perceptions of a specialty care appointment discussing diagnostic plans. METHODS: Caregivers (N=177) completed the GBMM scale and other measures prior to their child's initial specialty clinic visit. After the visit, they reported their perceptions of the visit, including patient-centeredness and satisfaction with care. Providers (N=6) reported their perceptions of patient engagement. RESULTS: Multivariable linear regression showed that higher caregiver GBMM was associated with caregivers' lower satisfaction with care (p<0.01) and more negative perceptions of every domain of patient-centeredness (p=0.001-0.04). Multilevel modeling showed that higher caregiver GBMM was associated with more negative provider perceptions of caregivers' preparedness to participate in care (p=0.03), likely treatment compliance (p=0.03), and relevance of questions asked during visit (p=0.04). CONCLUSION: Our findings extend evidence for detrimental effects of GBMM on patient satisfaction to caregivers of pediatric patients and offer new evidence for associations with healthcare providers' perceptions of caregivers' engagement with care.

The Parent PrU: A measure to assess personal utility of pediatric genomic results.

PURPOSE: We aimed to adapt and validate an existing patient-reported outcome measure, the personal-utility (PrU) scale, for use in the pediatric genomic context. METHODS: We adapted the adult version of the PrU and obtained feedback from 6 parents whose child had undergone sequencing. The resulting measure, the Parent PrU, was administered to parents of children in 4 pediatric cohorts of the Clinical Sequencing Evidence-Generating Research consortium after they received their children's genomic results. We investigated the measure's structural validity and internal consistency. RESULTS: We conducted a principal-axis factor analysis with oblimin rotation on data from 755 participants to determine structural validity. These analyses yielded a 3-factor solution, accounting for 76% of the variance in the 16 items. We used Cronbach's α to assess the internal consistency of each factor: (1) child benefits (α = .95), (2) affective parent benefits (α = .90), and (3) parent control (α = .94). CONCLUSION: Our evidence suggests that the Parent PrU scale has potential as a measure for assessing parent-reported personal utility of their children's genomic results. Additional research is needed to further validate the Parent PrU scale, including by comparing its findings with utility assessments reported by clinicians and children themselves.

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 vs 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. More than 90% reported satisfaction across all items measuring support and interaction during sessions. Participants self-reporting Hispanic/Latino or Black/African American race and ethnicity compared with 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 return of results 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.

Measuring perceived utility of genomic sequencing: Development and validation of the GENEtic Utility (GENE-U) scale for pediatric diagnostic testing.

PURPOSE: Measuring the effects of genomic sequencing (GS) on patients and families is critical for translational research. We aimed to develop and validate an instrument to assess parents' perceived utility of pediatric diagnostic GS. METHODS: Informed by a 5-domain conceptual model, the study comprised 5 steps: (1) item writing, (2) cognitive testing, (3) pilot testing and item reduction, (4) psychometric testing, and (5) evaluation of construct validity. Parents of pediatric patients who had received results of clinically indicated GS participated in structured cognitive interviews and 2 rounds of surveys. After eliminating items based on theory and quantitative performance, we conducted an exploratory factor analysis and calculated Pearson correlations with related instruments. RESULTS: We derived the 21-item Pediatric Diagnostic version of the GENEtic Utility (GENE-U) scale, which has a 2-factor structure that includes an Informational Utility subscale (16 items, α = 0.91) and an Emotional Utility subscale (5 items, α = 0.71). Scores can be summed to calculate a Total scale score (α = 0.87). The Informational Utility subscale was strongly associated with empowerment and personal utility of GS, and the Emotional Utility subscale was moderately associated with psychosocial impact and depression and anxiety. CONCLUSION: The pediatric diagnostic GENE-U scale demonstrated good psychometric performance in this initial evaluation and could be a useful tool for translational genomics researchers, warranting additional validation.

Measuring perceived utility of genomic sequencing: Development and validation of the GENEtic Utility (GENE-U) scale for adult screening.

PURPOSE: As population-based screening programs to identify genetic conditions in adults using genomic sequencing (GS) are increasingly available, validated patient-centered outcome measures are needed to understand participants' experience. We aimed to develop and validate an instrument to assess the perceived utility of GS in the context of adult screening. METHODS: Informed by a 5-domain conceptual model, we used a 5-step approach to instrument development and validation: (1) item writing, (2) cognitive testing, (3) pilot testing and item reduction, (4) psychometric testing, and (5) evaluation of construct validity. Adults undergoing risk-based or population-based GS who had received GS results as part of ongoing research studies participated in structured cognitive interviews and 2 rounds of surveys. After item pool refinement, we conducted an exploratory factor analysis and calculated Pearson correlations with related instruments. RESULTS: We derived the 18-item Adult Screening version of the GENEtic Utility scale (total sum score α = .87). Mirroring the Pediatric Diagnostic version, the instrument has a 2-factor structure, including an Informational Utility subscale (14 items, α = .89) and an Emotional Utility subscale (4 items, α = .75). The Informational Utility subscale was strongly associated with empowerment and personal utility of GS. Correlations of the Emotional Utility subscale with psychosocial impact and anxiety and depression were weak to moderate. CONCLUSION: Initial psychometric testing of the Adult Screening GENEtic Utility scale demonstrates its promise, and additional validation in translational genomics research is warranted.

Measuring health-related quality of life in children with suspected genetic conditions: validation of the PedsQL proxy-report versions.

PURPOSE: Measuring health-related quality of life (HRQoL) of children with suspected genetic conditions is important for understanding the effect of interventions such as genomic sequencing (GS). The Pediatric Quality of Life Inventory (PedsQL) is a widely used generic measure of HRQoL in pediatric patients, but its psychometric properties have not yet been evaluated in children undergoing diagnostic GS. METHODS: In this cross-sectional study, we surveyed caregivers at the time of their child's enrollment into GS research studies as part of the Clinical Sequencing Evidence Generating Research (CSER) consortium. To evaluate structural validity of the PedsQL 4.0 Generic Core Scales and PedsQL Infant Scales parent proxy-report versions, we performed a confirmatory factor analysis of the hypothesized factor structure. To evaluate convergent validity, we examined correlations between caregivers' reports of their child's health, assessed using the EQ VAS, and PedsQL scores by child age. We conducted linear regression analyses to examine whether age moderated the association between caregiver-reported child health and PedsQL scores. We assessed reliability using Cronbach's alpha. RESULTS: We analyzed data for 766 patients across all PedsQL age group versions (1-12 months through 13-18 years). Model fit failed to meet criteria for good fit, even after modification. Neither age group (categorical) nor age (continuous) significantly moderated associations between PedsQL scores and caregiver-reported child health. Cronbach's alphas indicated satisfactory internal consistency for most PedsQL scales. CONCLUSION: The PedsQL Generic Core Scales and Infant Scales may be appropriate to measure HRQoL in pediatric patients with suspected genetic conditions across a wide age range. While we found evidence of acceptable internal consistency and preliminary convergent validity in this sample, there were some potential problems with structural validity and reliability that require further attention.

Effect of an mHealth intervention on physical activity outcomes among young adult cancer survivors: The IMPACT randomized controlled trial.

BACKGROUND: Physical inactivity is common in young adult cancer survivors (YACS), but evidence regarding effects of physical activity (PA) interventions among YACS is limited. The IMproving Physical Activity after Cancer Treatment (IMPACT) trial evaluated a theory-based mobile PA intervention on total PA minutes/week (primary) and secondary outcomes (moderate-to-vigorous PA [MVPA], light PA, steps, sedentary behaviors) at 6 months in YACS. METHODS: YACS (N = 280) were randomized to an intervention group or self-help group. All participants received digital tools (activity tracker, smart scale, access to arm-specific Facebook group) and an individual video chat session. Intervention participants also received a 6-month program with behavioral lessons, adaptive goal-setting, tailored feedback, tailored text messages, and Facebook prompts. PA was assessed via accelerometry and questionnaires at baseline and 6 months. Generalized estimating equation analyses tested between-group differences in changes over time. RESULTS: Of 280 YACS, 251 (90%) completed the 6-month accelerometry measures. Accelerometer-measured total PA minutes/week changed from 1974.26 at baseline to 2024.34 at 6 months in the intervention (mean change, 55.14 [95% CI, -40.91 to 151.19]) and from 1814.93 to 1877.68 in the self-help group (40.94 [95% CI, -62.14 to 144.02]; between-group p = .84). Increases in MVPA were +24.67 minutes/week (95% CI, 14.77-34.57) in the intervention versus +11.41 minutes/week in the self-help (95% CI, 1.44-21.38; between-group p = .07). CONCLUSION: Although the intervention did not result in significant differences in total PA, the increase in MVPA relative to the self-help group might be associated with important health benefits. Future research should examine moderators to identify for whom, and under what conditions, the intervention might be effective. CLINICALTRIALS: gov Identifier: NCT03569605. PLAIN LANGUAGE SUMMARY: Physical inactivity is common in young adult cancer survivors. However, few interventions have focused on helping young adult cancer survivors to get more physical activity. The IMproving Physical Activity after Cancer Treatment trial compared a mobile health physical activity intervention with a self-help group on total amount of physical activity at 6 months in a nationwide sample of young adult cancer survivors. Intervention participants did not improve their total amount of physical activity, but they did increase their moderate-to-vigorous intensity physical activity by twice as much as the self-help participants. This increase in activity may be associated with health benefits.

Genomic Sequencing for Newborn Screening: Results of the NC NEXUS Project.

Newborn screening (NBS) was established as a public health program in the 1960s and is crucial for facilitating detection of certain medical conditions in which early intervention can prevent serious, life-threatening health problems. Genomic sequencing can potentially expand the screening for rare hereditary disorders, but many questions surround its possible use for this purpose. We examined the use of exome sequencing (ES) for NBS in the North Carolina Newborn Exome Sequencing for Universal Screening (NC NEXUS) project, comparing the yield from ES used in a screening versus a diagnostic context. We enrolled healthy newborns and children with metabolic diseases or hearing loss (106 participants total). ES confirmed the participant's underlying diagnosis in 15 out of 17 (88%) children with metabolic disorders and in 5 out of 28 (∼18%) children with hearing loss. We discovered actionable findings in four participants that would not have been detected by standard NBS. A subset of parents was eligible to receive additional information for their child about childhood-onset conditions with low or no clinical actionability, clinically actionable adult-onset conditions, and carrier status for autosomal-recessive conditions. We found pathogenic variants associated with hereditary breast and/or ovarian cancer in two children, a likely pathogenic variant in the gene associated with Lowe syndrome in one child, and an average of 1.8 reportable variants per child for carrier results. These results highlight the benefits and limitations of using genomic sequencing for NBS and the challenges of using such technology in future precision medicine approaches.

Diagnostic yield and psychological outcomes among women pursuing trio-exome sequencing: Do women with recurrent anomalous fetal phenotypes experience more negative psychological outcomes?

PURPOSE: To describe psychological outcomes among people with recurrent anomalous pregnancies pursuing trio-exome sequencing (exome sequencing (ES)) compared to those with one affected. METHODS: We analyzed data from a prospective ES cohort, enrolling patients with major fetal anomaly and normal microarray. Participants completed validated scales before and after ES. We (1) compared responses of those with multiple anomalous pregnancies to those with one affected and (2) conducted linear regression to examine associations between multiple affected pregnancies and post-ES constructs. RESULTS: Of 166 trios, 61 (37%) received results from ES. Forty (24%) had more than one affected pregnancy and 45% of those received a result explaining the fetal phenotype. All participants had clinically significant presequencing generalized psychological distress. For the 93 who completed the post-ES surveys, those with multiple affected pregnancies had higher psychological adaptation scores but worse test related distress scores (9.3 (6.2) versus 7.1(5.6), p = 0.12) and (14.3 (1.5) versus 15.4 (1.4), p = 0.01). In linear regression models, there were no significant differences in post-ES constructs after adjusting for clinically relevant covariates. CONCLUSIONS: All individuals experienced significant generalized psychological distress in the pre-ES period, extending our knowledge of how pregnancy history contributes to parental sequencing outcomes.

Greater Social Isolation and Social Constraints Prior to Hematopoietic Stem Cell Transplant Are Associated with Greater Anxiety and Depressive Symptoms.

BACKGROUND: Hematopoietic stem cell transplantation (hereafter "HCT") is a physically and psychologically difficult treatment for patients with hematological cancers. This study examined relationships among patients' reports of pre-transplant social isolation, social constraints, and psychological distress. METHOD: We used baseline data from a multisite randomized controlled trial evaluating the effects of expressive helping writing to reduce physical and emotional symptoms in HCT patients. We collected data prior to randomization and before either allogenic or autologous HCT using validated scales to assess social constraints, social isolation, anxiety, and depressive symptoms. We analyzed data using bivariate analysis and multivariate linear regression. We also explored whether social isolation mediated the effect of social constraints on both of our outcomes: anxiety and depressive symptoms. RESULTS: Among 259 adults recruited prior to transplant, 43.6% were women (mean age = 57.42 years, SD = 12.34 years). In multivariate analysis controlling for relevant covariates, both social isolation (ß = 0.24, p < 0.001) and social constraints (ß = 0.28, p < 0.001) were associated with anxiety. When both social constraints and social isolation were in the model, only greater social isolation (ß = 0.79, p < 0.001) was associated with depressive symptoms. Social isolation fully mediated the association between social constraints and anxiety and depressive symptoms. CONCLUSION: For patients awaiting either allogenic or autologous HCT, the negative association between social constraints and anxiety and depressive symptoms may be related, in part, to the mechanism of perceived social isolation. Interventions prior to and during HCT are needed to support patients' psychological health and sense of social connectedness.

Stem Cell Transplant Experiences Among Hispanic/Latinx Patients: A Qualitative Analysis.

BACKGROUND: Hispanic/Latinx (H/L) patients with cancer treated with stem cell transplant are vulnerable to adverse outcomes, including higher mortality. This study explored their unmet transplant needs, barriers, and facilitators. METHODS: Eighteen English- or Spanish-speaking H/L patients (M age = 59.2) who had a transplant in the past year were interviewed about their transplant experience and rated their interest in receiving information about transplant topics (0 = not at all to 10 = extremely). RESULTS: Content analysis revealed five main themes: (1) pre-transplant barriers and concerns; (2) complex relationships with medical teams; (3) informational mismatch; (4) impacts on daily life after transplant; and (5) methods of coping. Participants were most interested in information about ways of coping with transplant (M = 9.11, SD = 1.45) and words of hope and encouragement (M = 9.05, SD = 1.80). At just above the scale's midpoint, they were least interested in information about side effects and unintended consequences of transplant (M = 5.61, SD = 3.85). CONCLUSIONS: Cultural factors, social determinants, and structural inequalities give rise to unique needs in this growing patient population. Healthcare team members and researchers can better meet the needs of H/L transplant recipients through attention to described considerations, such as financial barriers, communication difficulties, family dynamics, and coping styles.

Intervening in the Cancer Care System: An Analysis of Equity-Focused Nurse Navigation and Patient-Reported Outcomes.

BACKGROUND: Nurse navigation can improve quality of cancer care and reduce racial disparities in care outcomes. Addressing persistent structurally-rooted disparities requires research on strategies that support patients by prompting structural changes to systems of care. We applied a novel conceptualization of social support to an analysis of racial equity-focused navigation and patient-reported outcomes. METHOD: We applied an antiracism lens to create a theory-informed definition of system-facing social support: intervening in a care system on a patient's behalf. Participants were adults with early-stage breast or lung cancer, who racially identified as Black or White, and received specialized nurse navigation (n = 155). We coded navigators' clinical notes (n = 3,251) to identify instances of system-facing support. We then estimated models to examine system-facing support in relation to race, perceived racism in health care settings, and mental health. RESULTS: Twelve percent of navigators' clinical notes documented system-facing support. Black participants received more system-facing support than White participants, on average (b = 0.78, 95% confidence interval [CI]: [0.25, 1.31]). The interaction of race*system-facing support was significant in a model predicting perceived racism in health care settings at the end of the study controlling for baseline scores (b = 0.05, 95% CI [0.01, 0.09]). Trends in simple slopes indicated that among Black participants, more system-facing support was associated with slightly more perceived racism; no association among White participants. DISCUSSION: The term system-facing support highlights navigators' role in advocating for patients within the care system. More research is needed to validate the construct system-facing support and examine its utility in interventions to advance health care equity.

The Burden of COVID-19 on Caregivers of Children with Suspected Genetic Conditions: A Therapeutic Odyssey.

AIMS: Children with disabilities and rare or undiagnosed conditions and their families have faced numerous hardships of living during the COVID-19 pandemic. For those with undiagnosed conditions, the diagnostic odyssey can be long, expensive, and marked by uncertainty. We, therefore, sought to understand whether and how COVID-19 impacted the trajectory of children's care. METHODS: We conducted semi-structured qualitative interviews with 25 caregivers who, prior to the pandemic, were on a diagnostic odyssey for their children. RESULTS: Most caregivers did not report any interruptions to their child's diagnostic odyssey. The greatest impact was access to therapy services, including the suspension or loss of their child's in-person therapeutic care and difficulties with virtual therapies. This therapy gap caused caregivers to fear that their children were not making progress. CONCLUSION: Although much has been written about the challenges of diagnostic odysseys for children and their families, this study illustrates the importance of expanding the focus of these studies to include therapeutic odysseys. Because therapeutic odysseys continue regardless of whether diagnoses are made, future research should investigate how to support caregivers through children's therapies within and outside of the COVID-19 context.

Optimizing use of written peer support as a supportive resource in cancer: Focus group insights.

PURPOSE: Cancer survivors frequently describe wanting to learn from others who have had similar diagnoses or treatments (peer support). We conducted focus groups to investigate hematopoietic stem cell transplant survivors' attitudes and preferences regarding accessing written peer support through a website. Although written peer support does not allow for interpersonal interactions with peers, it could increase transplant recipients' access to evidence-based benefits of informational and emotional peer support. METHODS: We conducted four videoconference focus groups with 34 adult transplant survivors who were diverse in their medical and sociodemographic characteristics and geographic location. Discussions were recorded, transcribed, and content analyzed. RESULTS: Many participants reported need for information about transplant beyond what they received from their healthcare providers. Needs varied across participants, as did preferences for characteristics and timing of information optimally provided through peer support. Participants were enthusiastic about the value of written peer support but emphasized that it should be delivered in a way that accommodates variation in transplant experiences, underscores its trustworthiness, and pairs it with useful psychoeducational content. CONCLUSIONS: Findings provide guidance for making written peer support an accessible, supportive resource for transplant survivors. Future research should evaluate personalized online delivery of written peer support paired with psychoeducational content that enhances its benefits. IMPLICATIONS FOR CANCER SURVIVORS: Written peer support delivered online could be a useful, valued resource for transplant survivors.

Partner and Relationship Predictors of Longitudinal Physical Activity Trajectories Among Individuals with Osteoarthritis Using Latent Class Growth Analysis.

BACKGROUND: Physical activity reduces osteoarthritis symptoms, yet many individuals with the disease are insufficiently active. PURPOSE: We identified physical activity trajectories over 12 months of individuals with osteoarthritis and examined how their cohabiting spouses'/partners' baseline physical activity and relationship factors affected trajectory membership. METHODS: In this longitudinal observational study, we collected data from 168 adults with knee/hip osteoarthritis. We used latent class growth curve analysis to identify physical activity trajectories and logistic regression to predict trajectory membership using partners' physical activity, relationship satisfaction, and communal coping (belief that both partners are responsible for osteoarthritis management). Measures, including objectively assessed physical activity, were collected at baseline from the couple, who then received an educational class on physical activity and social support. Objectively assessed physical activity was also collected from individuals with osteoarthritis at 1 week, 3 months, 6 months, and 12 months post-baseline. RESULTS: Three trajectories were identified: stable active, increaser, and stable sedentary (24%, 40%, 37% of participants, respectively). Individuals with osteoarthritis with partners who were more active and who believed they alone were responsible for their osteoarthritis were more likely to follow the stable active (versus stable sedentary) trajectory. Those with partners who were less active and had higher relationship satisfaction were more likely to follow the increaser (vs. stable active) trajectory. CONCLUSIONS: Findings demonstrate the importance of considering partner and relationship factors in physical activity interventions for couples.

Parental motivations for and adaptation to trio-exome sequencing in a prospective prenatal testing cohort: Beyond the diagnosis.

PURPOSE: To understand motivations for and parental interpretation of results from trio-exome sequencing (ES) for fetal anomalies with a negative standard genetic diagnosis. METHODS: Analysis of an ongoing, prospective prenatal trio-ES study of pregnancies with ultrasound-identified congenital anomalies and lack of a standard genetic diagnosis. After determination of pregnancy disposition, participants completed questionnaires and a semi-structured interview pre- and post-sequencing. Interviews were analyzed using a constructivist grounded theory methodology to identify themes. Associations between themes and ES result were also examined. RESULTS: One hundred twenty-six trios have been sequenced. Of those, 45 (36%) resulted in fetal diagnosis. One hundred twenty-five women completed pre-sequencing surveys, and 91 women completed post-sequencing surveys. The main themes identified include (1) variable reasons to pursue ES, (2) limited expectations but high hopes from ES, (3) parental adaptation to uncertain results, (4) impact on personal health and reproduction, and (5) gratitude for the process. CONCLUSION: Participants pursued ES for various reasons, most often to identify a diagnosis and guide reproduction. Post-sequencing, most participants described the process, their interpretation of results, and the impact of receiving the results. Less frequently, but of most concern, participants expressed anxiety about testing and implications for themselves, relationships, and other family members, thus identifying an area of high need for additional support among patients undergoing prenatal ES.

The Clinical Sequencing Evidence-Generating Research Consortium: Integrating Genomic Sequencing in Diverse and Medically Underserved Populations.

The Clinical Sequencing Evidence-Generating Research (CSER) consortium, now in its second funding cycle, is investigating the effectiveness of integrating genomic (exome or genome) sequencing into the clinical care of diverse and medically underserved individuals in a variety of healthcare settings and disease states. The consortium comprises a coordinating center, six funded extramural clinical projects, and an ongoing National Human Genome Research Institute (NHGRI) intramural project. Collectively, these projects aim to enroll and sequence over 6,100 participants in four years. At least 60% of participants will be of non-European ancestry or from underserved settings, with the goal of diversifying the populations that are providing an evidence base for genomic medicine. Five of the six clinical projects are enrolling pediatric patients with various phenotypes. One of these five projects is also enrolling couples whose fetus has a structural anomaly, and the sixth project is enrolling adults at risk for hereditary cancer. The ongoing NHGRI intramural project has enrolled primarily healthy adults. Goals of the consortium include assessing the clinical utility of genomic sequencing, exploring medical follow up and cascade testing of relatives, and evaluating patient-provider-laboratory level interactions that influence the use of this technology. The findings from the CSER consortium will offer patients, healthcare systems, and policymakers a clearer understanding of the opportunities and challenges of providing genomic medicine in diverse populations and settings, and contribute evidence toward developing best practices for the delivery of clinically useful and cost-effective genomic sequencing in diverse healthcare settings.

Impact of prenatal exome sequencing for fetal genetic diagnosis on maternal psychological outcomes and decisional conflict in a prospective cohort.

PURPOSE: To evaluate associations between prenatal trio exome sequencing (trio-ES) and psychological outcomes among women with an anomalous pregnancy. METHODS: Trio-ES study enrolling patients with major fetal anomaly and normal microarray. Women completed self-reported measures and free response interviews at two timepoints: pre- (1) and post- (2) sequencing. Pre-sequencing responses were compared with post-sequencing responses; post-sequencing responses were stratified by women who received trio-ES results that may explain fetal findings, secondary findings (medically actionable or couples with heterozygous variants for the same recessive disorder), or negative results. RESULTS: One hundred fifteen trios were enrolled. Of those, 41/115 (35.7%) received results from trio-ES, including 36 (31.3%) who received results that may explain the fetal phenotype. These women had greater post-sequencing distress compared with women who received negative results, including generalized distress (p = 0.03) and test-related distress (p = 0.2); they also had worse psychological adaptation to results (p = 0.001). Genomic knowledge did not change from pre- to post-sequencing (p = 0.51). CONCLUSION: Women show more distress after receiving trio-ES results compared with those who do not, suggesting that women receiving results may need additional support or counseling to inform current and future reproductive decisions.

Changes in Identification of Possible Pain Coping Strategies by People with Osteoarthritis who Complete Web-based Pain Coping Skills Training.

BACKGROUND: We previously demonstrated that automated, Web-based pain coping skills training (PCST) can reduce osteoarthritis pain. The present secondary analyses examined whether this program also changed coping strategies participants identified for use in hypothetical pain-related situations. METHOD: People with hip/knee osteoarthritis (n = 107) were randomized to Web-based PCST or standard care control. At baseline and post-intervention, they reported their pain severity and impairment, then completed a task in which they described how they would cope with pain in four hypothetical pain-related situations, also reporting their perceived risk for pain and self-efficacy for managing it. We coded the generated coping strategies into counts of adaptive behavioral, maladaptive behavioral, adaptive cognitive, and discrete adaptive coping strategies (coping repertoire). RESULTS: Compared to the control arm, Web-based PCST decreased the number of maladaptive behavioral strategies generated (p = 0.002) while increasing the number of adaptive behavioral strategies generated (p = 0.006), likelihood of generating at least one adaptive cognitive strategy (p = 0.01), and the size of participants' coping repertoire (p = 0.009). Several of these changes were associated with changes in pain outcomes (ps = 0.01 to 0.65). Web-based PCST also reduced perceived risk for pain in the situations (p = 0.03) and increased self-efficacy for avoiding pain in similar situations (p < 0.001). CONCLUSION: Salutary changes found in this study appear to reflect intervention-concordant learning.