Significance testing in ridge regression for genetic data.

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Implementation of an Online Glaucoma-Specific Quality of Life Computerized Adaptive Test System in a US Glaucoma Hospital

PURPOSE: The feasibility of implementing a computerized adaptive test (CAT) system in routine clinical care in ophthalmology has not been assessed. We evaluated the implementation of a glaucoma-specific CAT (GlauCAT) in outpatients at Massachusetts Eye and Ear Institute. METHODS: In this implementation study (July 2020-April 2021), 216 adults (mean ± SD age 64.8 ± 15.3 years; 56.0% women) completed six adaptive GlauCAT quality of life (QOL) tests on an internet-enabled tablet at the clinic. A real-time printable report summarizing domain scores was shared with physicians prior to consultation. The implementation was evaluated using Proctor's outcomes: acceptability (patient satisfaction); appropriateness (independent complete rate [%]); feasibility (acceptance rate [%]; completion time); and fidelity (percentage of patients discussing GlauCAT results with their physician). Physician barriers/facilitators were explored using open-ended questions. RESULTS: Patients' mean ± SD satisfaction score was 3.5 ± 0.5 of 4, with >95% of patients willing to recommend it to others. Of the 216 (89.2%) patients accepting to participate, 173 (80%) completed GlauCAT independently. Patients took 8 minutes and 5 seconds (median) to complete all 6 GlauCAT tests. Almost two-thirds (n = 136/216) of the patients reported discussing their GlauCAT results with their doctor. Physicians described the GlauCAT summary report as helpful and user-friendly, although lack of time and uncertainty about how to action information were reported. CONCLUSIONS: Pilot implementation of six GlauCAT QOL tests in glaucoma outpatient clinics was feasible and acceptable. Integration of GlauCAT with electronic medical records (EMRs) and evaluation of long-term implementation outcomes are needed. TRANSLATIONAL RELEVANCE: GlauCAT's multiple outcomes and low test-taking burden makes it attractive for measuring glaucoma-specific QOL in routine clinical care

Analysis of HCM in an understudied population reveals a new mechanism of pathogenicity

Hypertrophic Cardiomyopathy (HCM) is an inherited disease characterized by genetic and phenotypic heterogeneity. MYH7 represents one of the main sarcomere-encoding genes associated with HCM. Missense variants in this gene cause HCM through gain-of-function actions, whereby variants produce an abnormal activated protein which incorporates into the sarcomere as a "poison peptide". Here we report a frameshift variant in MYH7, c.5769delG, that is associated with HCM in an Egyptian cohort (3.3%) compared with ethnically-matched controls. This variant is absent from previously published large-scale Caucasian HCM cohorts. We further demonstrate strong evidence of co-segregation of c.5769delG with HCM in a large family (LOD score: 3.01). The predicted sequence of the variant MYH7 transcript shows that the frameshift results in a premature termination codon (PTC) downstream of the last exon-exon junction of the gene that is expected to escape nonsense-mediated decay (NMD). RNA sequencing of myocardial tissue obtained from a patient with the variant during surgical myectomy confirmed the expression of the variant MYH7 transcript. Our analysis reveals a new mechanism of pathogenicity in the understudied Egyptian population whereby distal PTC in MYH7 may lead to the expression of an abnormal protein

Micafungin for Candida Albicans Pacemaker-Associated Endocarditis: A Case Report and Review of the Literature

We report on the treatment with micafungin of a pacemaker-associated endocarditis due to Candida albicans. Antifungal therapy was able to reduce vegetation size from 5 to 1 cm making possible the transvenous removal of the device without a high risk of pulmonary embolism. Noteworthy, a high micafungin concentration was documented into the lead vegetation (10 mu g/g of vegetation tissue) and this may have contributed to the striking size reduction of vegetation