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- Walsh, Roddy, et al.
(författare)
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Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls
- 2021
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Ingår i: Genetics in Medicine. - : Nature Publishing Group. - 1098-3600 .- 1530-0366. ; 23:1, s. 47-58
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate.Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants.Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 x 10(-18)) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 x 10(-13)). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency.Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.
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| 2. |
- Carlsson, Sigrid, 1982, et al.
(författare)
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Shared Medical Appointments for Prostate Cancer Active Surveillance Followup Visits
- 2021
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Ingår i: Urology Practice. - : Ovid Technologies (Wolters Kluwer Health). - 2352-0779. ; 8:5, s. 541-545
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: To accommodate for the rapidly increasing patient volume and followup visits of men with prostate cancer on active surveillance (AS), we carried out a quality improvement project to secure high-quality care and enhance patient experience. Methods: We proposed an innovative clinic systems redesign-"shared medical appointments" (SMAs)-in which multiple patients were seen in a group format at the same time by the health care team led by a urologist leading the Institution's AS program. Results: We piloted four SMAs during July-November 2019. Running the SMAs was feasible and improved the contact time for each patient while at the same time being time and resource efficient for the health care providers and using the standard billing processes. The group dynamic was open and pleasant. The majority of patients rated their overall experience with SMA as excellent. Almost all patients responded that they were likely or very likely to attend another SMA in the future. All patients said that they would either definitely or probably recommend this visit type to a friend of family member with prostate cancer. Most patients rated their overall satisfaction with the SMA as extremely high. Conclusions: Utilizing SMAs for AS followup visits was feasible and acceptable. Our promising findings suggest that SMAs can ensure high-quality patient care. Well-controlled studies comparing SMAs to individual usual care visits should be conducted with end points including knowledge, patient and staff satisfaction, anxiety and quality-of-life outcomes, AS adherence, process measures and resource utilization.
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