The Patient Protection and Affordable Care Act (PPACA) is slowly transforming the U.S. Health Care System from a fee-for-service structure, which reimburses providers based on the quantity of patient ...encounters, to a new structure that emphasizes the value of care. Since value can be interpreted differently among various stakeholders, quality measures have been established by government and nonprofit sources. These quality measures serve as agreed-upon criteria by which to measure the achievement of value in health care. While these measures help to improve the quality of health care, they can also be burdensome to physicians and health care organizations. Implementation of quality measurement programs requires the involvement of highly intelligent people who think about what to measure, what to focus on, and how to accomplish outcomes. Thus, the process of selecting measures and compiling recommendations (reports) can be time consuming, complicated, and expensive.
Applying SELP coursework fundamentals, key process activities outlined by INCOSE, and the DoD Architectural Framework, a quality measure information system was developed. The primary business objective (top level requirement) of the project was to reduce the cost and improve the quality of the measure selection and report generation processes. First, fundamental systems engineering principles were applied to understand the problem, conduct a lean analysis, identify stakeholders' needs, and derive a set of requirements to meet the primary business objective. Subsequently, five alternative solutions were evaluated to identify a preferred solution that could best meet the primary business objective while minimizing risk. The DoD Architectural Framework and course material from Integration of Hybrid Hardware and Software Systems (SELP 560) was then applied to develop, represent, and understand the information system architecture. Finally, leveraging Management Information Systems Coursework (MBAA 609), a system prototype was created utilizing Microsoft Access.
The system prototype demonstrated a capability to reduce the cost and improve the quality of the health care quality measure selection and report generation processes. Utilizing pre-selected associations between various quality measures and categories of care, comprehensive quality measure reports can be generated in a matter of seconds for many categories of medical care. These comprehensive reports serve to educate users about various quality measures and to aid administrators in the development of comprehensive quality measurement programs. In one particular example, health care organizations will utilize the generated quality measure reports for the purpose of redesigning compensation and incentive pay for physicians and health care executives. In this particular example, estimates show that the system prototype is expected to reduce the labor associated with measure research and selection by approximately 49%, resulting in thousands of dollars of estimated savings. Additionally, the system will automate complicated measure search processes, which will increase the quality and consistency of the reported data.
Heparan sulfate (HS) is a cell surface polysaccharide recently identified as a coreceptor with the ACE2 protein for the S1 spike protein on SARS-CoV-2 virus, providing a tractable new therapeutic ...target. Clinically used heparins demonstrate an inhibitory activity but have an anticoagulant activity and are supply-limited, necessitating alternative solutions. Here, we show that synthetic HS mimetic pixatimod (PG545), a cancer drug candidate, binds and destabilizes the SARS-CoV-2 spike protein receptor binding domain and directly inhibits its binding to ACE2, consistent with molecular modeling identification of multiple molecular contacts and overlapping pixatimod and ACE2 binding sites. Assays with multiple clinical isolates of SARS-CoV-2 virus show that pixatimod potently inhibits the infection of monkey Vero E6 cells and physiologically relevant human bronchial epithelial cells at safe therapeutic concentrations. Pixatimod also retained broad potency against variants of concern (VOC) including B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Furthermore, in a K18-hACE2 mouse model, pixatimod significantly reduced SARS-CoV-2 viral titers in the upper respiratory tract and virus-induced weight loss. This demonstration of potent anti-SARS-CoV-2 activity tolerant to emerging mutations establishes proof-of-concept for targeting the HS–Spike protein–ACE2 axis with synthetic HS mimetics and provides a strong rationale for clinical investigation of pixatimod as a potential multimodal therapeutic for COVID-19.
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