Does genomic risk information motivate people to change their behavior?

The recent flood of information about new gene variants associated with chronic disease risk from genome-wide association studies has understandably led to enthusiasm that genetic discoveries could reduce disease burdens and increase the availability of direct-to-consumer tests offering risk information. However, we suggest caution: if it is to be any benefit to health, genetic risk information needs to prompt individuals to pursue risk-reduction behaviors, yet early evidence suggests that genetic risk may not be an effective motivator of behavior change. It is not clear how genetic information will inform risk-based behavioral intervention, or what harms might occur. Research is needed that examines the behavioral consequences of genetic risk knowledge in the context of other motivators and social conditions, as well as research that determines the subgroups of people most likely to be motivated, in order to inform policy decisions about emerging genetic susceptibility tests. Without such research, it will not be possible to determine the appropriate health care uses for such tests, the impact on health care resources from consumer-initiated testing, or the criteria for truthful advertising of direct-to-consumer tests

Understanding the Return of Genomic Sequencing Results Process: Content Review of Participant Summary Letters in the eMERGE Research Network

A challenge in returning genomic test results to research participants is how best to communicate complex and clinically nuanced findings to participants in a manner that is scalable to the large numbers of participants enrolled. The purpose of this study was to examine the features of genetic results letters produced at each Electronic Medical Records and Genomics (eMERGE3) Network site to assess their readability and content. Letters were collected from each site, and a qualitative analysis of letter content and a quantitative analysis of readability statistics were performed. Because letters were produced independently at each eMERGE site, significant heterogeneity in readability and content was found. The content of letters varied widely from a baseline of notifying participants that results existed to more detailed information about positive or negative results, as well as materials for sharing with family members. Most letters were significantly above the Centers for Disease Control-suggested reading level for health communication. While continued effort should be applied to make letters easier to understand, the ongoing challenge of explaining complex genomic information, the implications of negative test results, and the uncertainty that comes with some types of test and result makes simplifying letter text challenging

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Conceptions of Legacy Among People Making Treatment Choices for Serious Illness: Protocol for a Scoping Review

BackgroundLegacy—what one leaves behind and how one hopes to be remembered after death—is an unexplored and important dimension of decision-making for people facing serious illnesses. A preliminary literature review suggests that patients facing serious illness consider legacy when making medical decisions, for example, forgoing expensive treatment with limited or unknown clinical benefit to preserve one’s inheritance for their children. To date, very little is known about the conceptual foundations of legacy. No conceptual frameworks exist that provide a comprehensive understanding of how legacy considerations relate to patient choices about their medical care. ObjectiveThe objective of this scoping review is to understand the extent and type of research addressing the concept of legacy by people facing serious illness to inform a conceptual framework of legacy and patient treatment choices. MethodsThis protocol follows the guidelines put forth by Levac et al, which expands the framework introduced by Arksey and O’Malley, as well as the Joanna Briggs Institute Reviewer’s manual. This scoping review will explore several electronic databases including PubMed, Medline, CINAHL, Cochrane Library, PsycINFO, and others and will include legacy-specific gray literature, including dissertation research available via ProQuest. An initial search will be conducted in English-language literature from 1990 to the present with selected keywords to identify relevant articles and refine the search strategy. After the search strategy has been finalized, 2 independent reviewers will undertake a 2-part study selection process. In the first step, reviewers will screen article titles and abstracts to identify the eligibility of each article based on predetermined exclusion or inclusion criteria. A third senior reviewer will arbitrate discrepancies regarding inclusions or exclusions. During the second step, the full texts will be screened by 2 reviewers, and only relevant articles will be kept. Relevant study data will be extracted, collated, and charted to summarize the key findings related to the construct of legacy. ResultsThis study will identify how people facing serious illness define legacy, and how their thinking about legacy impacts the choices they make about their medical treatments. We will note gaps in the literature base. The findings of this study will inform a conceptual model that outlines how ideas about legacy impact the patient’s treatment choices. The results of this study will be submitted to an indexed journal. ConclusionsVery little is known about the role of legacy in the treatment decisions of patients across the continuum of serious illness. In particular, no comprehensive conceptual model exists that would provide an understanding of how legacy is considered by people making decisions about their care during serious illness. This study will be among the first to construct a conceptual model detailing how considerations of legacy impact medical decision-making for people facing or living with serious illnesses. International Registered Report Identifier (IRRID)DERR1-10.2196/4079

Health Care Systems Research Network Twin Cohort and its Potential Utility

Background: Family-based studies have historically been considered a powerful strategy when understanding the etiologies of human disease, especially those influenced by genetics. A gold standard in family-based study design includes twin studies due to the unique genetic relationships between twin siblings, but these unique familial relationships are relatively rare and difficult to recruit. Herein we demonstrate that electronic health record (EHR) systems across multiple Health Care Systems Research Network (HCSRN) sites can identify twin families. We further show the utility of such twin cohorts in research using twins identified in Marshfield Clinic’s EHR. Methods: Twins were predicted by searching for patients who shared a common birthdate and last name along with a common home address, contact information or billing account. The twin prediction algorithm was applied to four different HCSRN sites, including Marshfield Clinic, Group Health Cooperative, Geisinger Health System and Meyers Primary Care Institute. In Marshfield Clinic twins, clinical phenotypes were defined by diagnostic ICD-9 coding. For each phenotype, a measure of familial aggregation and relative risk (RR) was calculated by assessing disease concordance in twin families. To further assess potential genetic etiologies, we compared familial aggregation in opposite-sex twins (dizygotic twins) and same-sex twins (enriched for monozygotic twins). Results: A total of 21,699 families of twins (43,398 individuals) were identified across four HCSRN sites, including 8,242 families of twins from Marshfield Clinic’s EHR. Of the 5,598 phenotypes assessed by familial aggregation analysis, 1,222 phenotypes were statistically significant (P \u3c 8.9E-6). When simply measuring relative risks across all diseases, 91% of phenotypes had relative risk \u3e 1. There was a 4.2-fold enrichment of disease concordance in same-sex twins compared to opposite-sex twins for phenotypes with the largest relative risks. Many of these phenotypes were likely influenced by genetic factors. Conclusion: This study has generated one of the world’s largest cohorts of twins. Unique to this population is the linkage to extensive phenotypic data through an EHR across multiple health care institutions. More broadly, with a significant proportion of diseases aggregating in families of twins, these results may emphasize the significant benefit of incorporating family data when predicting, preventing and treating many diseases for the advancement of precision medicine

Impact of the Childhood Vaccine Discussion Format over Time on Immunization Status

Objective: Presumptive formats to initiate childhood vaccine discussions (e.g. “Well we have to do some shots.”) have been associated with increased vaccine acceptance after one visit compared to participatory formats (e.g. “How do you feel about vaccines?”). We characterize discussion format patterns over time and the impact of their repeated use on vaccine acceptance. Methods: We conducted a longitudinal prospective cohort study of children of vaccine-hesitant parents enrolled in a Seattle-based integrated health system. After the child’s 2, 4, and 6 month visits, parents reported the format their child’s provider used to begin the vaccine discussion (presumptive, participatory, or other). Our outcome was the percentage of days under-immunized of the child at 8 months old for 6 recommended vaccines. We used linear regression and generalized estimating equations to test the association of discussion format and immunization status. Results: We enrolled 73 parent/child dyads and obtained data from 82%, 73%, and 53% after the 2, 4, and 6 month visits, respectively. Overall, 65% of parents received presumptive formats at ≥1 visit and 42% received participatory formats at ≥1 visit. Parental receipt of presumptive formats at 1 and ≥2 visits (vs. no receipt) was associated with significantly less underimmunization of the child, while receipt of participatory formats at ≥2 visits was associated with significantly more under-immunization. Visit-specific use of participatory (vs. presumptive) formats was associated with a child being 10.1% (95% CI: 0.3, 19.8; P=.04) more days underimmunized (amounting to, on average, 98 more days under-immunized for all 6 vaccines combined). Conclusions: Presumptive (vs. participatory) discussion formats are associated with increased immunization