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The Return of Actionable Variants Empirical (RAVE) Study, a Mayo Clinic Genomic Medicine Implementation Study: Design and Initial Results.

ABSTRACT: OBJECTIVES:To identify clinically actionable genetic variants from targeted sequencing of 68 disease-related genes, estimate their penetrance, and assess the impact of disclosing results to participants and providers. PATIENTS AND METHODS:The Return of Actionable Variants Empirical (RAVE) Study investigates outcomes following the return of pathogenic/likely pathogenic (P/LP) variants in 68 disease-related genes. The study was initiated in December 2016 and is ongoing. Targeted sequencing was performed in 2533 individuals with hyperlipidemia or colon polyps. The electronic health records (EHRs) of participants carrying P/LP variants in 36 cardiovascular disease (CVD) genes were manually reviewed to ascertain the presence of relevant traits. Clinical outcomes, health care utilization, family communication, and ethical and psychosocial implications of disclosure of genomic results are being assessed by surveys, telephone interviews, and EHR review. RESULTS:Of 29,208 variants in the 68 genes, 1915 were rare (frequency <1%) and putatively functional, and 102 of these (60 in 36 CVD genes) were labeled P/LP based on the American College of Medical Genetics and Genomics framework. Manual review of the EHRs of participants (n=73 with P/LP variants in CVD genes) revealed that 33 had the expected trait(s); however, only 6 of 45 participants with non-familial hypercholesterolemia (FH) P/LP variants had the expected traits. CONCLUSION:Expected traits were present in 13% of participants with P/LP variants in non-FH CVD genes, suggesting low penetrance; this estimate may change with additional testing performed as part of the clinical evaluation. Ongoing analyses of the RAVE Study will inform best practices for genomic medicine.

SUBMITTER: Kullo IJ

PROVIDER: S-EPMC6652203 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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The Return of Actionable Variants Empirical (RAVE) Study, a Mayo Clinic Genomic Medicine Implementation Study: Design and Initial Results.

Kullo Iftikhar J IJ Olson Janet J Fan Xiao X Jose Merin M Safarova Maya M Radecki Breitkopf Carmen C Winkler Erin E Kochan David C DC Snipes Sara S Pacyna Joel E JE Carney Meaghan M Chute Christopher G CG Gupta Jyoti J Jose Sheethal S Venner Eric E Murugan Mullai M Jiang Yunyun Y Zordok Magdi M Farwati Medhat M Philogene Maraisha M Smith Erica E Shaibi Gabriel Q GQ Caraballo Pedro P Freimuth Robert R Lindor Noralane M NM Sharp Richard R Thibodeau Stephen N SN

Mayo Clinic proceedings 20181101 11

<h4>Objectives</h4>To identify clinically actionable genetic variants from targeted sequencing of 68 disease-related genes, estimate their penetrance, and assess the impact of disclosing results to participants and providers.<h4>Patients and methods</h4>The Return of Actionable Variants Empirical (RAVE) Study investigates outcomes following the return of pathogenic/likely pathogenic (P/LP) variants in 68 disease-related genes. The study was initiated in December 2016 and is ongoing. Targeted seq ...[more]

PMID: 30392543

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Project description:ObjectiveTo describe characteristics of a series of patients reporting prolonged symptoms after an infection with coronavirus disease 2019 (COVID-19).Patients and methodsThis study describes the multidisciplinary COVID-19 Activity Rehabilitation Program, established at Mayo Clinic to evaluate and treat patients with post-COVID syndrome, and reports the clinical characteristics of the first 100 patients receiving evaluation and management during the timeframe of June 1, 2020, and December 31, 2020.ResultsThe cohort consisted of 100 patients (mean age, 45.4±14.2 years; 68% women; mean body mass index, 30.2 kg/m2; presenting a mean of 93 days after infection). Common preexisting conditions were respiratory (23%) and mental health, including depression and/or anxiety (34%). Most (75%) had not been hospitalized for COVID-19. Common presenting symptoms ware fatigue (80%), respiratory complaints (59%), and neurological complaints (59%) followed by subjective cognitive impairment, sleep disturbance, and mental health symptoms. More than one-third of patients (34%) reported difficulties in performing basic activities of daily living. Only 1 in 3 patients had returned to unrestricted work duty at the time of the analysis. For most patients, laboratory and imaging tests showed no abnormalities or were nondiagnostic despite debilitating symptoms. Most patients required physical therapy, occupational therapy, or brain rehabilitation. Face-to-face and virtual care delivery modalities were feasible.ConclusionMost of the patients did not have COVID-19-related symptoms that were severe enough to require hospitalization, were younger than 65 years, and were more likely to be female, and most had no preexisting comorbidities before severe acute respiratory syndrome coronavirus 2 infection. Symptoms including mood disorders, fatigue, and perceived cognitive impairment resulted in severe negative impacts on resumption of functional and occupational activities in patients experiencing prolonged effects.

Project description:Telemedicine techniques can be used to address the rural-metropolitan disparity in acute stroke care. The Stroke Team Remote Evaluation Using a Digital Observation Camera (STRokE DOC) trial reported more accurate decision making for telemedicine consultations compared with telephone-only and that the California-based research network facilitated a high rate of thrombolysis use, improved data collection, low risk of complications, low technical complications, and favorable assessment times. The main objective of the STRokE DOC Arizona TIME (The Initial Mayo Clinic Experience) trial was to determine the feasibility of establishing, de novo, a single-hub, multirural spoke hospital telestroke research network across a large geographical area in Arizona by replicating the STRokE DOC protocol.Methods included prospective, single-hub, 2-spoke, randomized, blinded, controlled trial of a 2-way, site-independent, audiovisual telemedicine system designed for remote examination of adult patients with acute stroke versus telephone consultation to assess eligibility for treatment with intravenous thrombolysis. The primary outcome measure was whether the decision to give thrombolysis was correct. Secondary outcomes were rate of thrombolytic use, 90-day functional outcomes, incidence of intracerebral hemorrhages, and technical observations.From December 2007 to October 2008, 54 patients were assessed, 27 of whom were randomized to each arm. Mean National Institutes of Health Stroke Scale score at presentation was 7.3 (SD 6.2) points. No consultations were aborted; however, technical problems (74%) were prevalent in the telemedicine arm. Overall, the correct treatment decision was established in 87% of the consultations. Both modalities, telephone (89% correct) and telemedicine (85% correct), performed well. Intravenous thrombolytic treatment was used in 30% of the telemedicine and telephone consultations. Good functional outcomes at 90 days were not significantly different. There were no statistically significant differences in mortality (4% in telemedicine and 11% in telephone) or rates of intracerebral hemorrhage (4% in telemedicine and 0% in telephone).It is feasible to extend the original STRokE DOC trial protocol to a new state and establish an operational single-hub, multispoke rural hospital telestroke research network in Arizona. The trial was not designed to have sufficient power to detect a difference between the 2 consultative modes: telemedicine and telephone-only. Whether by telemedicine or telephone consultative modalities, there were appropriate treatment decisions, high rates of thrombolysis use, improved data collection, low rates of intracerebral hemorrhage, and equally favorable time requirements. The learning curve was steep for the hub and spoke personnel of the new telestroke network, as reflected by frequent technical problems. Overall, the results support the effectiveness of highly organized and structured stroke telemedicine networks for extending expert stroke care into rural remote communities lacking sufficient neurological expertise.

Dataset Information

The Return of Actionable Variants Empirical (RAVE) Study, a Mayo Clinic Genomic Medicine Implementation Study: Design and Initial Results.

Publications

The Return of Actionable Variants Empirical (RAVE) Study, a Mayo Clinic Genomic Medicine Implementation Study: Design and Initial Results.

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