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Kurt Christensen

Landmark Center, Department of Population Medicine
401 Park Drive, Suite 401 East, Boston, MA 02215
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Kurt Christensen
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Recent News

Recent News

I'm proud to announce that "Behavioral and psychological impact of genome sequencing: a pilot randomized trial of primary care and cardiology patients" is now in press at npj Genomic Medicine. It summarizes findings from a pilot study. The health behavior measures are crude, but it was fun to 
   - provide some initial (and interesting!) insight about providing polygenic risk estimates
   - test some ideas about how psychological responses might mediate associations between genetic risk disclosure and behavioral outcomes 

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Recent Publications
 

Recent Publications

Galbraith LN, Preys CL, Rehm HL, et al. Primary care providers' responses to unsolicited Lynch syndrome secondary findings of varying clinical significance. Genet Med. 2021;23 (10) :1977-1983.Abstract
PURPOSE: How primary care providers (PCPs) respond to genomic secondary findings (SFs) of varying clinical significance (pathogenic, uncertain significance [VUS], or benign) is unknown. METHODS: We randomized 148 American Academy of Family Physicians members to review three reports with varying significance for Lynch syndrome. Participants provided open-ended responses about the follow-up they would address and organized the SF reports and five other topics in the order they would prioritize responding to them (1 = highest priority, 6 = lowest priority). RESULTS: PCPs suggested referrals more often for pathogenic variants or VUS than benign variants (72% vs. 16%, p < 0.001). PCPs were also more likely to address further workup, like a colonoscopy or esophagogastroduodenoscopy, in response to pathogenic variants or VUS than benign variants (43% vs. 4%, p < 0.001). The likelihoods of addressing referrals or further workup were similar when PCPs reviewed pathogenic variants and VUS (both p > 0.46). SF reports were prioritized highest for pathogenic variants (2.7 for pathogenic variants, 3.6 for VUS, 4.3 for benign variants, all p ≤ 0.014). CONCLUSION: Results suggest that while PCPs appreciated the differences in clinical significance, disclosure of VUS as SFs would substantially increase downstream health-care utilization.
Yeh JM, Stout NK, Chaudhry A, et al. Universal newborn genetic screening for pediatric cancer predisposition syndromes: model-based insights. Genet Med. 2021;23 (7) :1366-1371.Abstract
PURPOSE: Genetic testing for pediatric cancer predisposition syndromes (CPS) could augment newborn screening programs, but with uncertain benefits and costs. METHODS: We developed a simulation model to evaluate universal screening for a CPS panel. Cohorts of US newborns were simulated under universal screening versus usual care. Using data from clinical studies, ClinVar, and gnomAD, the presence of pathogenic/likely pathogenic (P/LP) variants in RET, RB1, TP53, DICER1, SUFU, PTCH1, SMARCB1, WT1, APC, ALK, and PHOX2B were assigned at birth. Newborns with identified variants underwent guideline surveillance. Survival benefit was modeled via reductions in advanced disease, cancer deaths, and treatment-related late mortality, assuming 100% adherence. RESULTS: Among 3.7 million newborns, under usual care, 1,803 developed a CPS malignancy before age 20. With universal screening, 13.3% were identified at birth as at-risk due to P/LP variant detection and underwent surveillance, resulting in a 53.5% decrease in cancer deaths in P/LP heterozygotes and a 7.8% decrease among the entire cohort before age 20. Given a test cost of $55, universal screening cost $244,860 per life-year gained; with a $20 test, the cost fell to $99,430 per life-year gained. CONCLUSION: Population-based genetic testing of newborns may reduce mortality associated with pediatric cancers and could be cost-effective as sequencing costs decline.
Christensen KD, Bell M, Zawatsky CLB, et al. Precision Population Medicine in Primary Care: The Sanford Chip Experience. Front Genet. 2021;12 :626845.Abstract
Genetic testing has the potential to revolutionize primary care, but few health systems have developed the infrastructure to support precision population medicine applications or attempted to evaluate its impact on patient and provider outcomes. In 2018, Sanford Health, the nation's largest rural nonprofit health care system, began offering genetic testing to its primary care patients. To date, more than 11,000 patients have participated in the Sanford Chip Program, over 90% of whom have been identified with at least one informative pharmacogenomic variant, and about 1.5% of whom have been identified with a medically actionable predisposition for disease. This manuscript describes the rationale for offering the Sanford Chip, the programs and infrastructure implemented to support it, and evolving plans for research to evaluate its real-world impact.
Schwartz TS, Christensen KD, Uveges MK, et al. Effects of participation in a U.S. trial of newborn genomic sequencing on parents at risk for depression. J Genet Couns. 2021.Abstract
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.
Pereira S, Smith HS, Frankel LA, et al. Psychosocial Effect of Newborn Genomic Sequencing on Families in the BabySeq Project: A Randomized Clinical Trial. JAMA Pediatr. 2021.Abstract
Importance: Newborn genomic sequencing (nGS) may provide health benefits throughout the life span, but there are concerns that it could also have an unfavorable (ie, negative) psychosocial effect on families. Objective: To assess the psychosocial effect of nGS on families from the BabySeq Project, a randomized clinical trial evaluating the effect of nGS on the clinical care of newborns from well-baby nurseries and intensive care units. Design, Setting, and Participants: In this randomized clinical trial conducted from May 14, 2015, to May 21, 2019, at well-baby nurseries and intensive care units at 3 Boston, Massachusetts, area hospitals, 519 parents of 325 infants completed surveys at enrollment, immediately after disclosure of nGS results, and 3 and 10 months after results disclosure. Statistical analysis was performed on a per-protocol basis from January 16, 2019, to December 1, 2019. Intervention: Newborns were randomized to receive either standard newborn screening and a family history report (control group) or the same plus an nGS report of childhood-onset conditions and highly actionable adult-onset conditions (nGS group). Main Outcomes and Measures: Mean responses were compared between groups and, within the nGS group, between parents of children who received a monogenic disease risk finding and those who did not in 3 domains of psychosocial impact: parent-child relationship (Mother-to-Infant Bonding Scale), parents' relationship (Kansas Marital Satisfaction Scale), and parents' psychological distress (Edinburgh Postnatal Depression Scale anxiety subscale). Results: A total of 519 parents (275 women [53.0%]; mean [SD] age, 35.1 [4.5] years) were included in this study. Although mean scores differed for some outcomes at singular time points, generalized estimating equations models did not show meaningful differences in parent-child relationship (between-group difference in adjusted mean [SE] Mother-to-Infant Bonding Scale scores: postdisclosure, 0.04 [0.15]; 3 months, -0.18 [0.18]; 10 months, -0.07 [0.20]; joint P = .57) or parents' psychological distress (between-group ratio of adjusted mean [SE] Edinburgh Postnatal Depression Scale anxiety subscale scores: postdisclosure, 1.04 [0.08]; 3 months, 1.07 [0.11]; joint P = .80) response patterns between study groups over time for any measures analyzed in these 2 domains. Response patterns on one parents' relationship measure differed between groups over time (between-group difference in adjusted mean [SE] Kansas Marital Satisfaction Scale scores: postdisclosure, -0.19 [0.07]; 3 months, -0.04 [0.07]; and 10 months, -0.01 [0.08]; joint P = .02), but the effect decreased over time and no difference was observed on the conflict measure responses over time. We found no evidence of persistent negative psychosocial effect in any domain. Conclusions and Relevance: In this randomized clinical trial of nGS, there was no persistent negative psychosocial effect on families among those who received nGS nor among those who received a monogenic disease risk finding for their infant. Trial Registration: ClinicalTrials.gov Identifier: NCT02422511.
Christensen KD, Schonman EF, Robinson JO, et al. Behavioral and psychological impact of genome sequencing: a pilot randomized trial of primary care and cardiology patients. NPJ Genom Med. 2021;6 (1) :72.Abstract
Many expect genome sequencing (GS) to become routine in patient care and preventive medicine, but uncertainties remain about its ability to motivate participants to improve health behaviors and the psychological impact of disclosing results. In a pilot trial with exploratory analyses, we randomized 100 apparently healthy, primary-care participants and 100 cardiology participants to receive a review of their family histories of disease, either alone or in addition to GS analyses. GS results included polygenic risk information for eight cardiometabolic conditions. Overall, no differences were observed between the percentage of participants in the GS and control arms, who reported changes to health behaviors such as diet and exercise at 6 months post disclosure (48% vs. 36%, respectively, p = 0.104). In the GS arm, however, the odds of reporting a behavior change increased by 52% per high-risk polygenic prediction (p = 0.032). Mean anxiety and depression scores for GS and control arms had confidence intervals within equivalence margins of ±1.5. Mediation analyses suggested an indirect impact of GS on health behaviors by causing positive psychological responses (p ≤ 0.001). Findings suggest that GS did not distress participants. Future research on GS in more diverse populations is needed to confirm that it does not raise risks for psychological harms and to confirm the ability of polygenic risk predictions to motivate preventive behaviors.
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