When Genetic Screening is Useful, but not Used

In families with genetic disorders due to a known genetic mutation, presymptomatic genetic testing can lead to early detection and treatment of inherited disorders that may manifest later in life. The health benefits for family members at increased risk, however, is limited by the predictive value of the genetic test, the availability of effective treatments, and individuals’ and families’ willingness to undergo genetic testing in the first place. This Issue Brief describes the case of a genetic condition for which genetic screening of family members is clearly useful, and just as clearly underused. It explores the barriers to the use of genetic screening and has implications for the future as genetic technologies become more complex and produce more uncertainty

Genomic Variation: What Does It Mean?

New technologies have given us the ability to detect genomic variation at resolutions 50-100 times greater than earlier tests. The good news is that we can now detect variations that help explain developmental delays, autism, or multiple congenital anomalies in up to 20% of children. The bad news is that we can also detect small missing or extra pieces of chromosomes that remain unexplained: that is, we don’t know whether they have any clinical significance at all. The rapid pace of technological change may have outpaced the lab’s ability to interpret, providers’ abilities to explain, and patients’ abilities to understand the test results. This Issue Brief summarizes a series of studies examining the uncertainties revolving around chromosomal microarray testing, which has become the new standard of practice in genetic testing of children with unexplained anomalies

“Not Tied Up Neatly with a Bow”: Professionals’ Challenging Cases in Informed Consent for Genomic Sequencing

As the use of genomic technology has expanded in research and clinical settings, issues surrounding informed consent for genome and exome sequencing have surfaced. Despite the importance of informed consent, little is known about the specific challenges that professionals encounter when consenting patients or research participants for genomic sequencing. We interviewed 29 genetic counselors and research coordinators with considerable experience obtaining informed consent for genomic sequencing to understand their experiences and perspectives. As part of this interview, 24 interviewees discussed an informed consent case they found particularly memorable or challenging. We analyzed these case examples to determine the primary issue or challenge represented by each case. Challenges fell into two domains: participant understanding, and facilitating decisions about testing or research participation. Challenges related to participant understanding included varying levels of general and genomic literacy, difficulty managing participant expectations, and contextual factors that impeded participant understanding. Challenges related to facilitating decision-making included complicated family dynamics such as disagreement or coercion, situations in which it was unclear whether sequencing research would be a good use of participant time or resources, and situations in which the professional experienced disagreement or discomfort with participant decisions. The issues highlighted in these case examples are instructive in preparing genetics professionals to obtain informed consent for genomic sequencing

Erratum to: How Can Psychological Science Inform Research About Genetic Counseling for Clinical Genomic Sequencing?

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147141/1/jgc40372.pd

How Can Psychological Science Inform Research About Genetic Counseling for Clinical Genomic Sequencing?

Next generation genomic sequencing technologies (including whole genome or whole exome sequencing) are being increasingly applied to clinical care. Yet, the breadth and complexity of sequencing information raise questions about how best to communicate and return sequencing information to patients and families in ways that facilitate comprehension and optimal health decisions. Obtaining answers to such questions will require multidisciplinary research. In this paper, we focus on how psychological science research can address questions related to clinical genomic sequencing by explaining emotional, cognitive, and behavioral processes in response to different types of genomic sequencing information (e.g., diagnostic results and incidental findings). We highlight examples of psychological science that can be applied to genetic counseling research to inform the following questions: (1) What factors influence patients’ and providers’ informational needs for developing an accurate understanding of what genomic sequencing results do and do not mean?; (2) How and by whom should genomic sequencing results be communicated to patients and their family members?; and (3) How do patients and their families respond to uncertainties related to genomic information?Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147034/1/jgc40193.pd

Qualitative study of system-level factors related to genomic implementation

PURPOSE: Research on genomic medicine integration has focused on applications at the individual level, with less attention paid to implementation within clinical settings. Therefore, we conducted a qualitative study using the Consolidated Framework for Implementation Research (CFIR) to identify system-level factors that played a role in implementation of genomic medicine within Implementing GeNomics In PracTicE (IGNITE) Network projects. METHODS: Up to four study personnel, including principal investigators and study coordinators from each of six IGNITE projects, were interviewed using a semistructured interview guide that asked interviewees to describe study site(s), progress at each site, and factors facilitating or impeding project implementation. Interviews were coded following CFIR inner-setting constructs. RESULTS: Key barriers included (1) limitations in integrating genomic data and clinical decision support tools into electronic health records, (2) physician reluctance toward genomic research participation and clinical implementation due to a limited evidence base, (3) inadequate reimbursement for genomic medicine, (4) communication among and between investigators and clinicians, and (5) lack of clinical and leadership engagement. CONCLUSION: Implementation of genomic medicine is hindered by several system-level barriers to both research and practice. Addressing these barriers may serve as important facilitators for studying and implementing genomics in practice

Social and behavioral research in genomic sequencing: approaches from the Clinical Sequencing Exploratory Research Consortium Outcomes and Measures Working Group

The routine use of genomic sequencing in clinical medicine has the potential to dramatically alter patient care and medical outcomes. To fully understand the psychosocial and behavioral impact of sequencing integration into clinical practice, it is imperative that we identify the factors that influence sequencing-related decision making and patient outcomes. In an effort to develop a collaborative and conceptually grounded approach to studying sequencing adoption, members of the National Human Genome Research Institute's Clinical Sequencing Exploratory Research Consortium formed the Outcomes and Measures Working Group. Here we highlight the priority areas of investigation and psychosocial and behavioral outcomes identified by the Working Group. We also review some of the anticipated challenges to measurement in social and behavioral research related to genomic sequencing; opportunities for instrument development; and the importance of qualitative, quantitative, and mixed-method approaches. This work represents the early, shared efforts of multiple research teams as we strive to understand individuals' experiences with genomic sequencing. The resulting body of knowledge will guide recommendations for the optimal use of sequencing in clinical practice

Operationalizing the Reciprocal Engagement Model of Genetic Counseling Practice: a Framework for the Scalable Delivery of Genomic Counseling and Testing

With the advent of widespread genomic testing for diagnostic indications and disease risk assessment, there is increased need to optimize genetic counseling services to support the scalable delivery of precision medicine. Here, we describe how we operationalized the reciprocal engagement model of genetic counseling practice to develop a framework of counseling components and strategies for the delivery of genomic results. This framework was constructed based upon qualitative research with patients receiving genomic counseling following online receipt of potentially actionable complex disease and pharmacogenomics reports. Consultation with a transdisciplinary group of investigators, including practicing genetic counselors, was sought to ensure broad scope and applicability of these strategies for use with any large‐scale genomic testing effort. We preserve the provision of pre‐test education and informed consent as established in Mendelian/single‐gene disease genetic counseling practice. Following receipt of genomic results, patients are afforded the opportunity to tailor the counseling agenda by selecting the specific test results they wish to discuss, specifying questions for discussion, and indicating their preference for counseling modality. The genetic counselor uses these patient preferences to set the genomic counseling session and to personalize result communication and risk reduction recommendations. Tailored visual aids and result summary reports divide areas of risk (genetic variant, family history, lifestyle) for each disease to facilitate discussion of multiple disease risks. Post‐counseling, session summary reports are actively routed to both the patient and their physician team to encourage review and follow‐up. Given the breadth of genomic information potentially resulting from genomic testing, this framework is put forth as a starting point to meet the need for scalable genetic counseling services in the delivery of precision medicine.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147027/1/jgc41111.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147027/2/jgc41111-sup-0001.pd

Multiscale neural gradients reflect transdiagnostic effects of major psychiatric conditions on cortical morphology

It is increasingly recognized that multiple psychiatric conditions are underpinned by shared neural pathways, affecting similar brain systems. Here, we carried out a multiscale neural contextualization of shared alterations of cortical morphology across six major psychiatric conditions (autism spectrum disorder, attention deficit/hyperactivity disorder, major depression disorder, obsessive-compulsive disorder, bipolar disorder, and schizophrenia). Our framework cross-referenced shared morphological anomalies with respect to cortical myeloarchitecture and cytoarchitecture, as well as connectome and neurotransmitter organization. Pooling disease-related effects on MRI-based cortical thickness measures across six ENIGMA working groups, including a total of 28,546 participants (12,876 patients and 15,670 controls), we identified a cortex-wide dimension of morphological changes that described a sensory-fugal pattern, with paralimbic regions showing the most consistent alterations across conditions. The shared disease dimension was closely related to cortical gradients of microstructure as well as neurotransmitter axes, specifically cortex-wide variations in serotonin and dopamine. Multiple sensitivity analyses confirmed robustness with respect to slight variations in analytical choices. Our findings embed shared effects of common psychiatric conditions on brain structure in multiple scales of brain organization, and may provide insights into neural mechanisms of transdiagnostic vulnerability

Evaluating the effects of increasing physical activity to optimize rehabilitation outcomes in hospitalized older adults (MOVE Trial): Study protocol for a randomized controlled trial

Background: Older adults who have received inpatient rehabilitation often have significant mobility disability at discharge. Physical activity levels in rehabilitation are also low. It is hypothesized that providing increased physical activity to older people receiving hospital-based rehabilitation will lead to better mobility outcomes at discharge. Methods/Design: A single blind, parallel-group, multisite randomized controlled trial with blinded assessment of outcome and intention-to-treat analysis. The cost effectiveness of the intervention will also be examined. Older people (age >60 years) undergoing inpatient rehabilitation to improve mobility will be recruited from geriatric rehabilitation units at two Australian hospitals. A computer-generated blocked stratified randomization sequence will be used to assign 198 participants in a 1:1 ratio to either an 'enhanced physical activity' (intervention) group or a 'usual care plus' (control) group for the duration of their inpatient stay. Participants will receive usual care and either spend time each week performing additional physical activities such as standing or walking (intervention group) or performing an equal amount of social activities that have minimal impact on mobility such as card and board games (control group). Self-selected gait speed will be measured using a 6-meter walk test at discharge (primary outcome) and 6 months follow-up (secondary outcome). The study is powered to detect a 0.1 m/sec increase in self-selected gait speed in the intervention group at discharge. Additional measures of mobility (Timed Up and Go, De Morton Mobility Index), function (Functional Independence Measure) and quality of life will be obtained as secondary outcomes at discharge and tertiary outcomes at 6 months follow-up. The trial commenced recruitment on 28 January 2014. Discussion: This study will evaluate the efficacy and cost effectiveness of increasing physical activity in older people during inpatient rehabilitation. These results will assist in the development of evidenced-based rehabilitation programs for this population. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12613000884707(Date of registration 08 August 2013); ClinicalTrials.gov Identifier NCT01910740(Date of registration 22 July 2013)