William Jennings Bryan Dorn VA Medical Center

About: William Jennings Bryan Dorn VA Medical Center is a healthcare organization based out in Columbia, South Carolina, United States. It is known for research contribution in the topics: Population & Warfarin. The organization has 41 authors who have published 41 publications receiving 2091 citations. The organization is also known as: Dorn VAMC.

Decreased AGO2 and DCR1 in PBMCs from War Veterans with PTSD leads to diminished miRNA resulting in elevated inflammation.

Abstract: Chronic inflammation is a characteristic of post-traumatic stress disorder (PTSD). The initiation of inflammation and molecules involved are not yet clearly understood. Here, we provide compelling evidence that the inflammation seen in PTSD may result from the dysregulated miRNA processing pathway. Using microarray analysis with a discovery group of peripheral blood mononuclear cell (PBMC) samples from War Veterans with PTSD, we found 183 significantly downregulated miRNAs, several of which target numerous genes categorized to be pro-inflammatory in nature. This observation was further confirmed in a replicate group by including more samples. Furthermore, employing RNA-sequencing, quantitative real time PCR (qRT-PCR) and in vitro experiments, we found that Argonaute 2 (AGO2) and Dicer1 (DCR1) were downregulated in PTSD and provided convincing evidence that their downregulation affects mature miRNA generation. In addition, we noted that STAT3 transcript was reduced in PTSD and this was possibly responsible for reduced AGO2 and DCR1, which in turn affected miRNA synthesis. Furthermore, we observed that activation of CD4+ T cells or monocytes led to reduced mature miRNA availability. Finally, the inflammation seen in PTSD was associated with downregulated miRNA profile. Altogether, the current study demonstrates that the chronic inflammation seen in PTSD may be a result of dysregulated miRNA biogenesis pathway due to diminished expression of the key molecules like AGO2, DCR1 and STAT3.

IRB and Research Regulatory Delays Within the Military Health System: Do They Really Matter? And If So, Why and for Whom?

Abstract: Institutional review board (IRB) delays may hinder the successful completion of federally funded research in the U.S. military. When this happens, time-sensitive, mission-relevant questions go unanswered. Research participants face unnecessary burdens and risks if delays squeeze recruitment timelines, resulting in inadequate sample sizes for definitive analyses. More broadly, military members are exposed to untested or undertested interventions, implemented by well-intentioned leaders who bypass the research process altogether. To illustrate, we offer two case examples. We posit that IRB delays often appear in the service of managing institutional risk, rather than protecting research participants. Regulators may see more risk associated with moving quickly than risk related to delay, choosing to err on the side of bureaucracy. The authors of this article, all of whom are military-funded researchers, government stakeholders, and/or human subject protection experts, offer feasible recommendations to improve the IRB system and, ultimately, research within military, veteran, and civilian populations.

Bioactive Signaling in Next-Generation Pharmacotherapies for Heart Failure: A Review.

Abstract: Importance The standard pharmacotherapy for heart failure (HF), particularly HF with reduced ejection fraction (HFrEF), is primarily through the use of receptor antagonists, notably inhibition of the renin-angiotensin system by either angiotensin-converting enzyme inhibition or angiotensin II receptor blockade (ARB). However, the completed Prospective Comparison of ARNI With an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial identified that the use of a single molecule (sacubitril/valsartan), which is an ARB and the neutral endopeptidase inhibitor (NEPi) neprilysin, yielded improved clinical outcomes in HFrEF compared with angiotensin-converting enzyme inhibition alone. Observations This review examined specific bioactive signaling pathways that would be potentiated by NEPi and how these would affect key cardiovascular processes relevant to HFrEF. It also addressed potential additive/synergistic effects of ARB. A number of biological signaling pathways that may be potentiated by sacubitril/valsartan were identified, including some novel candidate molecules, which will act in a synergistic manner to favorably alter the natural history of HFrEF. Conclusions and Relevance This review identified that activation rather than inhibition of specific receptor pathways provided favorable cardiovascular effects that cannot be achieved by renin-angiotensin system inhibition alone. Thus, an entirely new avenue of translational and clinical research lies ahead in which HF pharmacotherapies will move beyond receptor antagonist strategies.

Impact of a Direct Oral Anticoagulant Population Management Tool on Anticoagulation Therapy Monitoring in Clinical Practice.

Abstract: Background: The optimal monitoring and follow-up strategy for long-term direct oral anticoagulant (DOAC) therapy has not been established. Historically, at our medical center, DOAC patients were referred to a clinical pharmacy specialist managed anticoagulation clinic (AC) for monitoring via regularly scheduled encounters (face-to-face or telephone). Objective: To determine if implementation of a DOAC Population Management Tool (PMT) designed to identify patients who most likely require clinical review and possibly intervention, would improve the efficacy (interventions per patient) and efficiency (time invested to generate an intervention) of monitoring over AC practices. Methods: The DOAC PMT group included patients flagged as potentially having a dosing issue or history of valve replacement. The AC group included patients who were scheduled for routine DOAC follow-up. The quantity and character of interventions made were prospectively recorded and compared. Results: A total of 399 patients were included. Data were collected for 131 patients identified by the DOAC PMT, resulting in a review of 170 flags with a total of 94 interventions or 0.55 interventions per flag reviewed. For the AC group, 268 patients were evaluated, leading to 53 interventions or 0.20 interventions per patient encounter (P < 0.001 for comparison). The time to generate an intervention was 16 minutes in the DOAC PMT versus 64 minutes for the AC group. Conclusion and Relevance: A population-based approach to DOAC monitoring represents a more effective and efficient strategy to reduce missed opportunities for interventions between follow-up appointments while also increasing clinic access, particularly for patients who require immediate attention.