Current Practices and the Provider Perspectives on Inconclusive Genetic Test Results for Osteogenesis Imperfecta in Children with Unexplained Fractures: ELSI Implications

2016 ◽  
Vol 44 (3) ◽  
pp. 514-519 ◽  
Author(s):  
Emily Youngblom ◽  
Mitzi Leah Murray ◽  
Peter H. Byers
Keyword(s):  
Genetic Testing ◽  
Osteogenesis Imperfecta ◽  
Bone Fractures ◽  
Clinical Care ◽  
Unintended Consequences ◽  
Test Results ◽  
Provider Perspectives ◽  
Fractures In Children ◽  
Genetic Test Results

Genetic testing can be used to determine if unexplained fractures in children could have resulted from a predisposition to bone fractures, e.g., osteogenesis imperfecta. However, uncertainty is introduced if a variant of unknown significance (VUS) is identified. Proper interpretation of VUS in these situations is critical because of its influence on clinical care and in court rulings. This study sought to understand how VUS are interpreted and used by practitioners when there is a differential diagnosis including both osteogenesis imperfecta and non-accidental injury.A 15-question survey was emailed to physicians who requested analysis of two genes, COL1A1 and COL1A2, from the University of Washington from 2005-2013 for patient cases involving suspicion of child abuse.Among the 89 participants, responses differed about when genetic testing should be ordered for osteogenesis imperfecta, who should be consulted about utilization of VUS test results, follow-up procedures, and who should receive the VUS results.There are no clear guidelines for how to interpret and follow up on VUS. In the legal setting, misinterpreted VUS could lead to unintended consequences and deleterious ramifications for family members. The need for better practice guidelines to help promote more equitable handling of these sensitive legal cases is clear.

scholarly journals IMProving care After inherited Cancer Testing (IMPACT) study: protocol of a randomized trial evaluating the efficacy of two interventions designed to improve cancer risk management and family communication of genetic test results

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Deborah Cragun ◽  
Jason Beckstead ◽  
Meagan Farmer ◽  
Gillian Hooker ◽  
Marleah Dean ◽  
...  
Keyword(s):  
Risk Management ◽  
Genetic Testing ◽  
Family Communication ◽  
Genetic Test ◽  
Test Results ◽  
Impact Study ◽  
Inherited Cancer ◽  
Genetic Test Results ◽  
Cancer Risk Management

Abstract Background Implementing genetic testing for inherited cancer predisposition into routine clinical care offers a tremendous opportunity for cancer prevention and early detection. However, genetic testing itself does not improve outcomes; rather, outcomes depend on implemented follow-up care. The IMPACT study is a hybrid type I randomized effectiveness-implementation trial to simultaneously evaluate the effectiveness of two interventions for individuals with inherited cancer predisposition focused on: 1) increasing family communication (FC) of genetic test results; and 2) improving engagement with guideline-based cancer risk management (CRM). Methods This prospective study will recruit a racially, geographically, and socioeconomically diverse population of individuals with a documented pathogenic/likely pathogenic (P/LP) variant in an inherited cancer gene. Eligible participants will be asked to complete an initial trial survey and randomly assigned to one of three arms: A) GeneSHARE, a website designed to increase FC of genetic test results; B) My Gene Counsel’s Living Lab Report, a digital tool designed to improve understanding of genetic test results and next steps, including CRM guidelines; or C) a control arm in which participants continue receiving standard care. Follow-up surveys will be conducted at 1, 3, and 12 months following randomization. These surveys include single-item measures, scales, and indices related to: 1) FC and CRM behaviors and behavioral factors following the COM-B theoretical framework (i.e., capability, opportunity, and motivation); 2) implementation outcomes (i.e., acceptability, appropriateness, exposure, and reach); and 3) other contextual factors (i.e., sociodemographic and clinical factors, and uncertainty, distress, and positive aspects of genetic test results). The primary outcomes are an increase in FC of genetic test results (Arm A) and improved engagement with guideline-based CRM without overtreatment or undertreatment (Arm B) by the 12-month follow-up survey. Discussion Our interventions are designed to shift the paradigm by which individuals with P/LP variants in inherited cancer genes are provided with information to enhance FC of genetic test results and engagement with guideline-based CRM. The information gathered through evaluating the effectiveness and implementation of these real-world approaches is needed to modify and scale up adaptive, stepped interventions that have the potential to maximize FC and CRM. Trial registration This study is registered at Clinicaltrials.gov (NCT04763915, date registered: February 21, 2021). Protocol version September 17th, 2021 Amendment Number 04.

Extended follow-up in the COGENT study: A randomized study of in-person versus telephone disclosure of cancer genetic test results.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1504-1504
Author(s):  
Angela R. Bradbury ◽  
Linda J. Patrick-Miller ◽  
Brian L. Egleston ◽  
Susan M. Domchek ◽  
Olufunmilayo I. Olopade ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Usual Care ◽  
Medical Management ◽  
Genetic Test ◽  
Knowledge Gain ◽  
Test Results ◽  
Gene Panel Testing ◽  
Genetic Test Results ◽  
Secondary Analyses

1504 Background: Alternative delivery models are needed in the era of Precision Medicine given a shortage of genetic providers and increasing utilization of genetic testing. Telephone disclosure (TD) of genetic test results, including multi-gene panel testing, is non-inferior to usual care in-person disclosure (IPD) for short-term distress but failed non-inferiority for knowledge. Longitudinal data including health behaviors are needed. Methods: 970 patients undergoing clinical genetic testing at 5 centers were randomly assigned to usual care IPD (n = 497) or TD (n = 473) of results in the COGENT Study (NCT01736345). Participants completed surveys after pre-test counseling, post-disclosure and at 6 and 12 months. We used non-inferiority tests for primary analyses and T-tests and logistic regressions for secondary analyses. Results: TD was not worse than IPD for anxiety both post-disclosure and at 6 months, but did not reach the non-inferiority threshold for knowledge at either time point. In secondary analyses there were no significant differences in anxiety, depression, or cancer worry between arms, but there was less knowledge gain at 6 (-0.41 v. +0.11 in IPD, p = 0.05) and 12 months (-0.34 v. +0.31 in IPD, p = 0.05) in the TD arm. In the TD arm, 195 (50%) returned for clinical follow-up with a physician to discuss medical management. Not returning for follow-up varied by site and was associated with a negative result, being male and non-white. Knowledge gain at 6 months was lower for those who did not return for follow-up (-0.77) compared to those who returned (-0.17, p = 0.08). There were no significant differences by arm at 6 and 12 months in performance of mammogram, breast MRI, colonoscopy or prophylactic surgeries. Conclusions: Distress is not unacceptably worse with TD, but knowledge failed the test for non-inferiority. Longitudinal knowledge declined more for those who did not return for medical follow-up, but uptake of screening and risk reducing behaviors did not differ by arm. Telephone disclosure of genetic test results, even MGPT, may be a reasonable alternative to in-person disclosure for patients who agree to return to meet with a provider for medical management recommendations. Clinical trial information: NCT01736345.

scholarly journals A framework for the evaluation of patients with congenital facial weakness

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Bryn D. Webb ◽  
Irini Manoli ◽  
Elizabeth C. Engle ◽  
Ethylin W. Jabs
Keyword(s):  
Genetic Counseling ◽  
Genetic Testing ◽  
Patient Population ◽  
Clinical Care ◽  
Diagnostic Algorithm ◽  
Accurate Diagnosis ◽  
Facial Weakness ◽  
The Core ◽  
Follow Up Studies

AbstractThere is a broad differential for patients presenting with congenital facial weakness, and initial misdiagnosis unfortunately is common for this phenotypic presentation. Here we present a framework to guide evaluation of patients with congenital facial weakness disorders to enable accurate diagnosis. The core categories of causes of congenital facial weakness include: neurogenic, neuromuscular junction, myopathic, and other. This diagnostic algorithm is presented, and physical exam considerations, additional follow-up studies and/or consultations, and appropriate genetic testing are discussed in detail. This framework should enable clinical geneticists, neurologists, and other rare disease specialists to feel prepared when encountering this patient population and guide diagnosis, genetic counseling, and clinical care.

scholarly journals Genetic Testing for Inherited Cardiovascular Diseases: A Scientific Statement From the American Heart Association

2020 ◽  
Vol 13 (4) ◽  
Author(s):  
Kiran Musunuru ◽  
Ray E. Hershberger ◽  
Sharlene M. Day ◽  
N. Jennifer Klinedinst ◽  
Andrew P. Landstrom ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Cardiovascular Diseases ◽  
Best Practices ◽  
Human Genetics ◽  
American Heart ◽  
Heart Association ◽  
Test Results ◽  
Lipid Disorders ◽  
Genetic Test Results ◽  
Scientific Statement

Advances in human genetics are improving the understanding of a variety of inherited cardiovascular diseases, including cardiomyopathies, arrhythmic disorders, vascular disorders, and lipid disorders such as familial hypercholesterolemia. However, not all cardiovascular practitioners are fully aware of the utility and potential pitfalls of incorporating genetic test results into the care of patients and their families. This statement summarizes current best practices with respect to genetic testing and its implications for the management of inherited cardiovascular diseases.

Randomized trial of web-based genetic education versus usual care in advanced cancer patients undergoing tumor genetic testing: Results from the ECOG-ACRIN NCI Community Oncology Research Program (NCORP; EAQ152) COMET trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2008-2008
Author(s):  
Angela R. Bradbury ◽  
Ju-Whei Lee ◽  
Jill B Gaieski ◽  
Shuli Li ◽  
Ilana F Gareen ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Usual Care ◽  
Genetic Test ◽  
Genetic Knowledge ◽  
Test Results ◽  
Advanced Cancer Patients ◽  
Web Based ◽  
Genetic Test Results ◽  
Anxiety Depression ◽  
Web Intervention

2008 Background: Enthusiasm for precision oncology may obscure the complex psychosocial and ethical considerations for tumor genetic testing. Low patient genetic knowledge has been documented and heightens the risk for adverse experiences. We developed a web-based intervention to increase genetic knowledge and decrease distress among advanced cancer patients undergoing tumor genetic testing. Methods: 594 patients (80% from NCORP Community Sites) were recruited and randomized to web-intervention (n = 293) or usual care (n = 301), prior to receipt of tumor genetic test results. Primary outcomes were genetic knowledge, anxiety, depression, and cancer-specific distress measured at T0 (prior to intervention), T1 (post-intervention), T2 (after receipt of tumor results) and T3 (3 months post receipt of tumor results). Secondary outcomes included satisfaction, regret and disappointment. The effect of web-intervention was evaluated using t-test, multiple linear regression and logistic regression, with an intent-to-treat approach. Results: Patients randomized to web-intervention had better knowledge improvement than those randomized to usual care (T1-T0, p < 0.0001; T2-T0, p = 0.003). No difference was observed in change scores for anxiety, depression or cancer-specific distress. To find the moderators of intervention effect (including sex, age, education, and literacy) two 2-way interactions were noted with statistical significance: higher depression among those in the intervention arm versus the control arm for patients with lower literacy (p = 0.03); and lower cancer-specific distress among women in the intervention arm than with usual care but no such effect noted in men (p = 0.01). 71% of patients reported receiving tumor test results and this did not differ by arm. Only 20% of patients reported regret and disappointment at T2, which was more likely for those without a mutation of interest (MOI) detected vs those with a MOI detected (OR = 2.08, 95% CI, 1.13 to 3.83, p = 0.02). Conclusions: Web-based education prior to receipt of tumor genetic test results increases patient understanding of tumor genetic testing. While the intervention did not significantly reduce distress, results suggest that women who received the intervention had lower cancer-specific distress than those with usual care. Future refinements to the web-intervention are needed to address low literacy groups, men and patients with no actionable results. Clinical trial information: NCT02823652.

scholarly journals To Warn or Not to Warn? Genetic Information, Families, and Physician Liability

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Jennifer L Gold
Keyword(s):  
Genetic Testing ◽  
Genetic Information ◽  
Third Party ◽  
Test Results ◽  
Physician Patient Relationship ◽  
Duty To Warn ◽  
Legal Obligations ◽  
Genetic Test Results ◽  
Physician Liability ◽  
Physician Patient

Genetic testing raises a number of legal issues. Physicians providing genetic testing may be faced with questions related to privacy, confidentiality, and the duty to warn. Because genetic information is by its very nature familial, genetic test results may have implications for others not privy to the particular physician-patient relationship. This can result in a legal and ethical quandary for the treating physician. This paper addresses questions with respect to genetic testing and the legal obligations of physicians. First, can a physician legally breach doctor-patient confidentiality to inform a family member of a genetic risk? Second, does the physician have a duty to warn the interested third party of that risk? And if the physician fails to warn that party, could s/he be found liable? These questions are addressed here in a comparative fashion, examining Canadian (and, where appropriate, American) common law as well as Quebec civil law. The paper concludes that physicians should be liable for the duty to warn in the context of genetic information only when the risk is serious, imminent, and avoidable.

scholarly journals Case-finding and genetic testing for familial hypercholesterolaemia in primary care

Heart ◽  
2021 ◽  
pp. heartjnl-2021-319742
Author(s):  
Nadeem Qureshi ◽  
Ralph Kwame Akyea ◽  
Brittany Dutton ◽  
Steve E Humphries ◽  
Hasidah Abdul Hamid ◽  
...  
Keyword(s):  
Primary Care ◽  
Genetic Testing ◽  
Familial Hypercholesterolaemia ◽  
Genetic Test ◽  
Significant Proportion ◽  
Case Finding ◽  
Test Results ◽  
Family History Questionnaire ◽  
Increased Risk ◽  
Genetic Test Results

ObjectiveFamilial hypercholesterolaemia (FH) is a common inherited disorder that remains mostly undetected in the general population. Through FH case-finding and direct access to genetic testing in primary care, this intervention study described the genetic and lipid profile of patients found at increased risk of FH and the outcomes in those with positive genetic test results.MethodsIn 14 Central England general practices, a novel case-finding tool (Familial Hypercholetserolaemia Case Ascertainment Tool, FAMCAT1) was applied to the electronic health records of 86 219 patients with cholesterol readings (44.5% of total practices’ population), identifying 3375 at increased risk of FH. Of these, a cohort of 336 consenting to completing Family History Questionnaire and detailed review of their clinical data, were offered FH genetic testing in primary care.ResultsGenetic testing was completed by 283 patients, newly identifying 16 with genetically confirmed FH and 10 with variants of unknown significance. All 26 (9%) were recommended for referral and 19 attended specialist assessment. In a further 153 (54%) patients, the test suggested polygenic hypercholesterolaemia who were managed in primary care. Total cholesterol and low-density lipoprotein-cholesterol levels were higher in those patients with FH-causing variants than those with other genetic test results (p=0.010 and p=0.002).ConclusionElectronic case-finding and genetic testing in primary care could improve identification of FH; and the better targeting of patients for specialist assessment. A significant proportion of patients identified at risk of FH are likely to have polygenic hypercholesterolaemia. There needs to be a clearer management plan for these individuals in primary care.Trial registration numberNCT03934320.

scholarly journals Phenotypic Profiling in Subjects Heterozygous for 1 of 2 Rare Variants in the Hypophosphatasia Gene (ALPL)

2020 ◽  
Vol 4 (8) ◽  
Author(s):  
Daniel R Tilden ◽  
Jonathan H Sheehan ◽  
John H Newman ◽  
Jens Meiler ◽  
John A Capra ◽  
...  
Keyword(s):  
Medical Records ◽  
Rare Variants ◽  
Serum Alkaline Phosphatase ◽  
Clinical Care ◽  
Test Results ◽  
Phenotype Correlation ◽  
Clinical Phenotypes ◽  
Pathogenic Variants ◽  
Genotype Phenotype Correlation ◽  
Genetic Test Results

Abstract Context Hypophosphatasia (HPP) is a syndrome marked by low serum alkaline phosphatase (AlkP) activity as well as musculoskeletal and/or dental disease. While the majority of subjects with HPP carry a pathogenic variant in the ALPL gene or its regulatory regions, individual pathogenic variants are often not tightly correlated with clinical symptomatology. We sought to better understand the genotype/phenotype correlation in HPP by examining the clinical and biochemical data of 37 subjects with 2 rare variants in ALPL. Methods Through BioVU, a DNA biobank that pairs individuals’ genetic information with their de-identified medical records, we identified subjects with 2 rare variants with distinct reported clinical phenotypes (p.D294A and p.T273M). We then performed a manual review of these subjects’ de-identified medical records along with computational modeling of protein structure to construct a genetic, biochemical and clinical phenotype for each subject and variant. Results Twenty subjects with the p.D294A variant and 17 with the p.T273M variant had sufficient data for analysis. Among subjects in our cohort with the p.D294A variant, 6 (30.0%) had both clinical bone disease and serum AlkP activity below 40 IU/L while 4 subjects (23.5%) with the p.T273M variant met the same criteria despite the distinct clinical phenotypes of these variants. Conclusions Given the loose genotype/phenotype correlation in HPP seen in our cohort, clinical context is crucial for the interpretation of genetic test results to guide clinical care in this population. Otherwise, over- or under-diagnosis may occur, resulting in misidentification of those who may benefit from additional screening and perhaps pharmacologic intervention.

scholarly journals Genetic testing for Parkinson disease

2020 ◽  
pp. 10.1212/CPJ.0000000000000831
Author(s):  
Lola Cook ◽  
Jeanine Schulze ◽  
Catherine Kopil ◽  
Tara Hastings ◽  
Anna Naito ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Parkinson Disease ◽  
Clinical Utility ◽  
Genetic Test ◽  
Genomic Testing ◽  
Test Results ◽  
Genetic Test Results ◽  
Genetic Status ◽  
Genetic Landscape ◽  
Busy Clinician

Purpose of reviewWith the advent of precision medicine and demand for genomic testing information, we may question whether it is time to offer genetic testing to our patients with Parkinson disease (PD). This review updates the current genetic landscape of PD, describes what genetic testing may offer, provides strategies for evaluating whom to test, and provides resources for the busy clinician.Recent findingsPatients with PD and their relatives, in various settings, have expressed an interest in learning their PD genetic status; however, physicians may be hesitant to widely offer testing due to the perceived low clinical utility of PD genetic test results. The rise of clinical trials available for patients with gene-specific PD and emerging information on genotype-phenotype correlations are starting to shift this discussion about testing.SummaryBy learning more about the various genetic testing options for PD and utility of results for patients and their care, clinicians may become more comfortable with widespread PD genetic testing in the research and clinical setting.

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