Open Source Pharmacokinetic/Pharmacodynamic Framework: Tutorial on the BioGears Engine

McDaniel, Matthew; Carter, Jennifer; Keller, Jonathan M.; White, Steven A.; Baird, Austin

doi:10.1002/psp4.12371

Cited by 9 publications

(7 citation statements)

References 42 publications

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“…We achieved bidirectional data integration and real-time sharing of physiologic and event data between a SMMARTS-compliant CVA simulator and the Immersive Modular Patient Care Team Trainer (IMPACTT) screen-based simulation system (VCOM3D, Orlando, FL) running a BioGears physiology engine. 17 In that integrated mode, the CVA simulator acted as a psychomotor skills user interface to a third-party screenbased simulator.…”

Section: Other Resultsmentioning

confidence: 99%

Smmarts

et al. 2020

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Introduction: Different simulators often share elements, resulting in different laboratories doing redundant work. This can lead to higher development and acquisition costs, proprietary, incompatible technology, lack of interoperability, and large inventories that reduce accessibility to the benefits of simulation. Simulation technology can become more affordable and scalable with open architecture and modular design. We describe the System of Modular Mixed and Augmented Reality Tracking Simulators (SMMARTS) open architecture, rapid development platform for designing and building modular procedural and guided-intervention simulators. Methods: A modular stand provides mechanical indexing (registration) of a modular anatomical block representing the anatomy relevant to the simulated intervention. A software development kit (SDK) integrated with the hardware (stand and hand-held tracked tools such as a needle and ultrasound probe) facilitates software development. The SMMARTS SDK at https://github.com/UF-CSSALT/SMMARTS-SDK developed in Unity Technologies' Unity game engine includes Arduino microcontroller and NDI's 6 degrees of freedom tracking connectivity along with software tools such as a replayer, user interface templates, 3D visualization of the virtual counterparts of physical elements, scoring monitors, cognitive aids, common error messages, and Experience Application Programming Interface compatibility. Results: We used SMMARTS to develop 9 different simulators internally (instructor-less central venous access currently deployed to Iraq, prostate biopsy, epidural loss-ofresistance, ventriculostomy, pterygopalatine fossa block, lumbar/chronic pain blocks, chest tube insertion) and externally (intravenous access). Discussion: As a living tool, SMMARTS now has sufficient functionality and benefits that we can share it to help clinicians and engineers focus more on content specific to learning objectives rather than back-end tasks.

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Section: Other Resultsmentioning

confidence: 99%

Smmarts

et al. 2020

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“…The circuit and graph constructs are the backbone of the physiology engine with numerous physiological models (such as a robust nervous system) developed on top of, and often influencing, this backbone (McDaniel et al, 2019b;McDaniel and Baird, 2019). These models include: a nervous system with baroreceptor and chemoreceptor feedback that modifies cardiovascular and respiratory activity; an active transport model that maintains ionic gradients across intracellular and extracellular compartments; a physiologically-based pharmacokinetic/pharmacodynamic (PBPK/PD) model that tracks the concentration-effect profile of numerous drugs (McDaniel et al, 2019a); a gastrointestinal model that determines rates of nutrient digestion and oral drug absorption; a renal feedback model that regulates urine production and substance filtration and reabsorption; and a metabolic consumption and production method that determines the energy demands of each organ. In addition, numerous injury models have been developed to influence the state of the patient ranging from acute hemorrhage to diabetes.…”

Section: Methodsmentioning

confidence: 99%

Whole Body PBPK Model of Nasal Naloxone Administration to Measure Repeat Dosing Requirements During Fentanyl Overdose

Baird

White

Das

et al. 2023

Preprint

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Opioid use in the United States and abroad is an endemic part of culture with yearly increases in overdose rates and deaths. As rates of overdose incidence increases, the use of the safe and effective reversal agent, naloxone, in the form of a nasal rescue spray is being fielded and used by emergency medical technicians (EMTs) at a greater and greater rate. Despite advances in deployment of these rescue products, deaths are continuing to increase. There is evidence that repeated dosing of a naloxone nasal spray (such as Narcan) is becoming more common due to the amount and type of opiate being abused. Despite the benefits of naloxone related to opioid reversals, we lack repeated dosing guidelines as a function of opiate and amount the patient has taken. Goal directed dosing is promising, where respiratory markers are being used as an indication of the patient recovery but require time and understanding by the EMT. We construct a whole-body model of the pharmacokinetics and dynamics of an opiate, fentanyl on respiratory depression. We then construct a model of nasal deposition and administration of naloxone to investigate repeat dosing requirements for large overdoses. We demonstrate that naloxone is highly effective at reversing respiratory symptoms of the patient and recommend dosing requirements as a function of opiate amount administered. By designing the model to include circulation and respiration we investigate physiological markers that may be used in goal directed therapy rescue treatments.

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“…BioGears contains a detailed whole-body PBPK/PD model that governs drug absorption, distribution, metabolism, and elimination. This model uses substance-specific physiochemical data to predict tissue-plasma partition coefficients and to generate a whole-body concentration profile for a drug (Clipp et al, 2016; McDaniel et al, 2019). The BioGears renal and hepatic systems handle drug metabolism and elimination.…”

Section: Methodsmentioning

confidence: 99%

A Whole-Body Mathematical Model of Sepsis Progression and Treatment Designed in the BioGears Physiology Engine

et al. 2019

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Sepsis is a debilitating condition associated with a high mortality rate that greatly strains hospital resources. Though advances have been made in improving sepsis diagnosis and treatment, our understanding of the disease is far from complete. Mathematical modeling of sepsis has the potential to explore underlying biological mechanisms and patient phenotypes that contribute to variability in septic patient outcomes. We developed a comprehensive, whole-body mathematical model of sepsis pathophysiology using the BioGears Engine, a robust open-source virtual human modeling project. We describe the development of a sepsis model and the physiologic response within the BioGears framework. We then define and simulate scenarios that compare sepsis treatment regimens. As such, we demonstrate the utility of this model as a tool to augment sepsis research and as a training platform to educate medical staff.

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Open Source Pharmacokinetic/Pharmacodynamic Framework: Tutorial on the BioGears Engine

Cited by 9 publications

References 42 publications

Smmarts

Smmarts

Whole Body PBPK Model of Nasal Naloxone Administration to Measure Repeat Dosing Requirements During Fentanyl Overdose

A Whole-Body Mathematical Model of Sepsis Progression and Treatment Designed in the BioGears Physiology Engine

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