Rice, F. | Search bioRxiv

bioRxiv2020

Investigating regions of shared genetic variation in attention deficit/hyperactivity disorder and major depressive disorder: A GWAS meta-analysis

Attention deficit/hyperactivity disorder (ADHD) demonstrates a high level of comorbidity with major depressive disorder (MDD). One possible contributor to this is that the two disorders show high genetic correlation. However, the specific regions of the genome that may be responsible for this overlap are unclear. To identify variants associated with both ADHD and MDD, we performed a meta-analysis of GWAS of ADHD and MDD. All genome wide significant (p=5x10-8) SNPs in the meta-analysis that were also strongly associated (p=5x10-4) independently with each disorder were followed up. These putatively pleiotropic SNPs were tested for additional associations across a broad range of phenotypes. Fourteen linkage disequilibrium-independent SNPs were identified that were associated with each disorder separately (p=5x10-4) and in the cross-disorder meta-analysis (p=5x10-8). Nine of these SNPs had not been reported previously in either individual GWAS and can be considered as novel signals. Evidence supported nine of the fourteen SNPs acting as eQTL and two of the SNPs as brain eQTL. Index SNPs and their genomic regions demonstrated associations with other mental health phenotypes. Through conducting meta-analysis on ADHD and MDD only, our results build upon the previously observed genetic correlation between ADHD and MDD and reveal novel regions of the genome that may be implicated in this overlap.

genetics↗

bioRxiv2018

Is it actionable? An Evaluation of the Rapid PCR-Based Blood Culture Identification Panel on the Management of Gram-Positive and Gram-Negative Blood Stream Infection

BackgroundThere is growing interest in the use of rapid blood culture identification (BCID) panels in antimicrobial stewardship programs (ASP). While many studies have looked at its clinical and economic utility, its comparative utility in gram-positive and gram-negative blood stream infections (BSI) have not been as well characterized.\n\nMethodsThe study was a quasi-experimental retrospective study at the Mayo Clinic in Phoenix, Arizona. All adult patients with positive blood cultures before BCID implementation (June 2015 to December 2015) and after BCID implementation (June 2016 to December 2016) were included. The outcomes of interest included: time to first appropriate antibiotic escalation, time to first appropriate antibiotic de-escalation, time to organism identification, LOS, infectious disease consultation, discharge disposition, and in-hospital mortality.\n\nResultsIn total, 203 patients were included in this study. There was a significant difference in the time to organism identification between pre- and post-BCID cohorts (27.1h vs. 3.3h, p<0.0001). BCID did not significantly reduce the time to first appropriate antimicrobial escalation or de-escalation for either GP-BSIs or GN-BSIs. Providers were more likely to escalate antimicrobial therapy in GP-BSIs after gram stain and more likely to de-escalate therapy in GN-BSIs after susceptibilities. While there were no significant differences in changes in antimicrobial therapy after organism identification by BCID, over a quarter of providers (28.1%) made changes after organism identification.\n\nConclusionsWhile BCID significantly reduced the time to identification for both GP-BSIs and GN-BSIs, BCID did not reduce the time to first appropriate antimicrobial escalation and de-escalation.

microbiology↗