Objective: To determine the prevalence of discordant cardiopulmonary function among patients with Duchenne muscular dystrophy (DMD) in our clinic. Methods: Retrospective chart review from 1999 to 2017. Inclusion criteria: DMD patients age ≥ 18 years, alive, with discordant cardiopulmonary function. No patients received glucocorticoid therapy. Discordant cardiopulmonary function was defined as either: good heart function (EF ≥ 40%) and bad lung function (FVC < 1 L) (Group A); or, bad heart function (EF < 40%) and good lung function (FVC ≥ 1 L) (Group B). Results: Among 74 eligible patients, 25 patients (34%) had discordant cardiopulmonary function (21 patients in Group A and 4 patients in Group B). Three dystrophin mutations were shared by >2 patients (nine patients with deletion of exon 44; three patients with deletion of exon 51; three patients with duplication of exon 2). Among the 15 patients with a shared genotype, eight patients (53%) had discordant cardiopulmonary function (five patients in group A, three patients in group B). Twenty-six patients had a deletion involving or distal to exon 45. Ten of these patients (38%) had discordant cardiopulmonary function (eight patients in Group A, two patients in Group B).Conclusion: In our cohort of DMD patients, discordant cardiopulmonary function was common (present in one-third of our patients), and the dystrophin genotype did not reliably predict a patient's cardiopulmonary phenotype. If confirmed by larger, multicenter studies, our findings have significant implications for predicting patient prognosis, evaluating DMD therapies, and designing new DMD therapies. K E Y W O R D S cardiomyopathy, Duchenne muscular dystrophy, genetic therapies, genotype, phenotype, pulmonary function
Objective To perform a systematic review of studies evaluating pharmacologic therapies for the cardiomyopathy of Duchenne muscular dystrophy (DMD). Methods: PubMed, Google Scholar, and Embase were searched through October 8, 2020. Articles were selected using pre‐determined criteria; 26 underwent detailed review by two co‐authors. Study quality was assessed with the Newcastle–Ottawa scoring system (NOS); GRADE assessment evaluated their overall clinical importance. Results There were few randomized controlled trials. Two of four trials of angiotensin converting enzyme inhibitors (ACEI) or ACEI plus beta‐blockers (BB) found improved LV function. Two of two randomized trials of aldosterone antagonists (AA), when added to ACEI and BB therapy, demonstrated less decline of LV circumferential strain over 1 year of treatment. Observational studies of ACEI and BB had differing patient ages, symptomatology, cohort size, study duration and baseline heart function. LV function, assessed via unblinded imaging, was the most frequent outcome measure. LV dysfunction improved in some trials but was unconfirmed in others. Class IV heart failure patients had transient improvement of symptoms and LVEF. Most NOS scores reflected a low level of study quality. The Grade certainty rating, used for the summation of studies, was between “low” and “moderate.” Conclusion Randomized trial evidence was inconsistent that either ACEI or BB or their combination improve LV function and/or alter progressive LV dysfunction. When ACEI and BB therapy are initiated for symptomatic Class IV heart failure, symptoms and LVEF improve transiently. AAs retard the rate of decline of LV function when initiated in younger DMD patients.
Frontline healthcare workers (HCW) are a high-risk population for SARS-CoV-2 infection. Here we present results from a large serosurveillance study of 10,019 asymptomatic HCW conducted during April-May 2020, in eight hospital medical centers across the state of Oregon, USA during the initial peak of the pandemic. Free and voluntary testing was performed at 14 +/- 3 day intervals, over a 4-week window at each site, utilizing a lab-developed ELISA based on the Epitope Diagnostics COVID-19 nucleocapsid IgG detection Kit. We identified 253 SARS-CoV-2 IgG seropositive individuals among 10,019 total participants, representing a cross-sectional seroprevalence of 2.53%. Subgroup analysis identified differential seropositivity by job role, ranging from 8.03% among housekeepers, odds ratio 3.17 (95% CI 1.59-5.71), to 0.00% among anesthesiologists, odds ratio 0.00 (95% CI 0-0.26), both of which were significant. Over the course of the study, 17 seroconversions (0.25%) and 101 seroreversions (1.50%) were identified. Self-reported SARS-CoV-2 swab qPCR testing, when compared with subsequent serology on study, showed only modest agreement, κ = 0.47 (95% CI 0.32-0.62). Overall, these findings demonstrate relatively low seroprevalence and very low seroconversion rates among HCW in Oregon, USA, over a period in which aggressive social distancing measures were in place. The high rate of seroreversion observed in this cohort, and the relatively high discordance between SARS-CoV-2 serology and swab qPCR, highlight limitations of current detection methods, and stress the need for development of novel assessment methodologies to more accurately identify exposure (and/or immunity) to SARS-CoV-2 in this population.
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