Improving Implementation of an Electronic Prescription System for COVID-19 Vaccination in the Czech Republic: Process Modeling Approach.

BACKGROUND: It is very difficult to find a consensus that will be accepted by most players when creating health care legislation. The Czech electronic prescription system was launched in 2011 and new functions were introduced in 2018. To ensure that these functions will not conflict with any other existing law, a process modeling tool based on the patent "Method and system for automated requirements modeling" was used successfully in the Czech Republic for the first time. OBJECTIVE: The aim of this project was to develop another successful application of process modeling to add COVID-19 vaccination records to the existing electronic prescription system. METHODS: The method employed was based on the mathematical theory of hierarchical state diagrams and process models. In the first step, sketches that record the results of informal discussions, interviews, meetings, and workshops were prepared. Subsequently, the architecture containing the main participants and their high-level interactions was drafted. Finally, detailed process diagrams were drawn. Each semiresult was discussed with all involved team members and stakeholders to incorporate all comments. By repeating this procedure, individual topics were gradually resolved and the areas of discussion were narrowed down until reaching complete agreement. RESULTS: This method proved to be faster, clearer, and significantly simpler than other methods. Owing to the use of graphic tools and symbols, the risk of errors, inaccuracies, and misunderstandings was significantly reduced. The outcome was used as an annex to the bill in the legislative process. One of the main benefits of this approach is gaining a higher level of understanding for all parties involved (ie, legislators, the medical community, patient organizations, and information technology professionals). The process architecture model in a form of a graphic scheme has proven to be a valuable communication platform and facilitated negotiation between stakeholders. Moreover, this model helped to avoid several inconsistencies that appeared during workshops and discussions. Our method worked successfully even when participants were from different knowledge areas. CONCLUSIONS: The vaccination record process model was drafted in 3 weeks and it took a total of 2 months to pass the bill. In comparison, the initial introduction of the electronic prescription system using conventional legislative methods took over 1 year, involving immediate creation of a text with legislative intent, followed by paragraph-by-section wording of the legislation that was commented on directly. These steps are repeated over and over, as any change in any part of the text has to be checked and rechecked within the entire document. Compared with conventional methods, we have shown that using our method for the process of modification of legislation related to such a complex issue as the integration of COVID-19 vaccination into an electronic prescription model significantly simplifies the preparation of a legislative standard.

Experience with Teaching Different Modeling Techniques on the example of Glucose Insulin Regulation Model.

In order to teach different modeling techniques we demonstrate equation-based, block-schema based, compartment and component-based modeling using acausal and object-oriented modeling language - Modelica. Hands-on implementation using all these techniques and comparing them towards same system (in our case glucose-insulin regulation) we teach pros and cons of each technique. Equation-based or block-schema based may be rapidly implemented from literature. However, compartment based or component-based models brings better understanding of modeled reality. When students have such experience, they tend to assess published papers more critically and do more complex system analysis.

Development of In-Browser Simulators for Medical Education: Introduction of a Novel Software Toolchain.

BACKGROUND: Simulators used in teaching are interactive applications comprising a mathematical model of the system under study and a graphical user interface (GUI) that allows the user to control the model inputs and visualize the model results in an intuitive and educational way. Well-designed simulators promote active learning, enhance problem-solving skills, and encourage collaboration and small group discussion. However, creating simulators for teaching purposes is a challenging process that requires many contributors including educators, modelers, graphic designers, and programmers. The availability of a toolchain of user-friendly software tools for building simulators can facilitate this complex task. OBJECTIVE: This paper aimed to describe an open-source software toolchain termed Bodylight.js that facilitates the creation of browser-based client-side simulators for teaching purposes, which are platform independent, do not require any installation, and can work offline. The toolchain interconnects state-of-the-art modeling tools with current Web technologies and is designed to be resilient to future changes in the software ecosystem. METHODS: We used several open-source Web technologies, namely, WebAssembly and JavaScript, combined with the power of the Modelica modeling language and deployed them on the internet with interactive animations built using Adobe Animate. RESULTS: Models are implemented in the Modelica language using either OpenModelica or Dassault Systèmes Dymola and exported to a standardized Functional Mock-up Unit (FMU) to ensure future compatibility. The C code from the FMU is further compiled to WebAssembly using Emscripten. Industry-standard Adobe Animate is used to create interactive animations. A new tool called Bodylight.js Composer was developed for the toolchain that enables one to create the final simulator by composing the GUI using animations, plots, and control elements in a drag-and-drop style and binding them to the model variables. The resulting simulators are stand-alone HyperText Markup Language files including JavaScript and WebAssembly. Several simulators for physiology education were created using the Bodylight.js toolchain and have been received with general acclaim by teachers and students alike, thus validating our approach. The Nephron, Circulation, and Pressure-Volume Loop simulators are presented in this paper. Bodylight.js is licensed under General Public License 3.0 and is free for anyone to use. CONCLUSIONS: Bodylight.js enables us to effectively develop teaching simulators. Armed with this technology, we intend to focus on the development of new simulators and interactive textbooks for medical education. Bodylight.js usage is not limited to developing simulators for medical education and can facilitate the development of simulators for teaching complex topics in a variety of different fields.

Testing Computer Models Predicting Human Responses to a High-Salt Diet.

Recently, mathematical models of human integrative physiology, derived from Guyton's classic 1972 model of the circulation, have been used to investigate potential mechanistic abnormalities mediating salt sensitivity and salt-induced hypertension. We performed validation testing of 2 of the most evolved derivatives of Guyton's 1972 model, Quantitative Cardiovascular Physiology-2005 and HumMod-3.0.4, to determine whether the models accurately predict sodium balance and hemodynamic responses of normal subjects to increases in salt intake within the real-life range of salt intake in humans. Neither model, nor the 1972 Guyton model, accurately predicts the usual changes in sodium balance, cardiac output, and systemic vascular resistance that normally occur in response to clinically realistic increases in salt intake. Furthermore, although both contemporary models are extensions of the 1972 Guyton model, testing revealed major inconsistencies between model predictions with respect to sodium balance and hemodynamic responses of normal subjects to short-term and long-term salt loading. These results demonstrate significant limitations with the hypotheses inherent in the Guyton models regarding the usual regulation of sodium balance, cardiac output, and vascular resistance in response to increased salt intake in normal salt-resistant humans. Accurate understanding of the normal responses to salt loading is a prerequisite for accurately establishing abnormal responses to salt loading. Accordingly, the present results raise concerns about the interpretation of studies of salt sensitivity with the various Guyton models. These findings indicate a need for continuing development of alternative models that incorporate mechanistic concepts of blood pressure regulation fundamentally different from those in the 1972 Guyton model and its contemporary derivatives.

Modern and traditional approaches combined into an effective gray-box mathematical model of full-blood acid-base.

BACKGROUND: The acidity of human body fluids, expressed by the pH, is physiologically regulated in a narrow range, which is required for the proper function of cellular metabolism. Acid-base disorders are common especially in intensive care, and the acid-base status is one of the vital clinical signs for the patient management. Because acid-base balance is connected to many bodily processes and regulations, complex mathematical models are needed to get insight into the mixed disorders and to act accordingly. The goal of this study is to develop a full-blood acid-base model, designed to be further integrated into more complex human physiology models. RESULTS: We have developed computationally simple and robust full-blood model, yet thorough enough to cover most of the common pathologies. Thanks to its simplicity and usage of Modelica language, it is suitable to be embedded within more elaborate systems. We achieved the simplification by a combination of behavioral Siggaard-Andersen's traditional approach for erythrocyte modeling and the mechanistic Stewart's physicochemical approach for plasma modeling. The resulting model is capable of providing variations in arterial pCO2, base excess, strong ion difference, hematocrit, plasma protein, phosphates and hemodilution/hemoconcentration, but insensitive to DPG and CO concentrations. CONCLUSIONS: This study presents a straightforward unification of Siggaard-Andersen's and Stewart's acid-base models. The resulting full-blood acid-base model is designed to be a core part of a complex dynamic whole-body acid-base and gas transfer model.

Surviving sepsis--a 3D integrative educational simulator.

Computer technology offers greater educational possibilities, notably simulation and virtual reality. This paper presents a technology which serves to integrate multiple modalities, namely 3D virtual reality, node-based simulator, Physiomodel explorer and explanatory physiological simulators employing Modelica language and Unity3D platform. This emerging tool chain should allow the authors to concentrate more on educational content instead of application development. The technology is demonstrated through Surviving sepsis educational scenario, targeted on Microsoft Windows Store platform.

Physiomodel - an integrative physiology in Modelica.

Physiomodel (http://www.physiomodel.org) is our reimplementation and extension of an integrative physiological model called HumMod 1.6 (http://www.hummod.org) using our Physiolibrary (http://www.physiolibrary.org). The computer language Modelica is well-suited to exactly formalize integrative physiology. Modelica is an equation-based, and object-oriented language for hybrid ordinary differential equations (http:// www.modelica.org). Almost every physiological term can be defined as a class in this language and can be instantiated as many times as it occurs in the body. Each class has a graphical icon for use in diagrams. These diagrams are self-describing; the Modelica code generated from them is the full representation of the underlying mathematical model. Special Modelica constructs of physical connectors from Physiolibrary allow us to create diagrams that are analogies of electrical circuits with Kirchhoff's laws. As electric currents and electric potentials are connected in electrical domain, so are molar flows and concentrations in the chemical domain; volumetric flows and pressures in the hydraulic domain; flows of heat energy and temperatures in the thermal domain; and changes and amounts of members in the population domain.

Modeling of short-term mechanism of arterial pressure control in the cardiovascular system: object-oriented and acausal approach.

This letter introduces an alternative approach to modeling the cardiovascular system with a short-term control mechanism published in Computers in Biology and Medicine, Vol. 47 (2014), pp. 104-112. We recommend using abstract components on a distinct physical level, separating the model into hydraulic components, subsystems of the cardiovascular system and individual subsystems of the control mechanism and scenario. We recommend utilizing an acausal modeling feature of Modelica language, which allows model variables to be expressed declaratively. Furthermore, the Modelica tool identifies which are the dependent and independent variables upon compilation. An example of our approach is introduced on several elementary components representing the hydraulic resistance to fluid flow and the elastic response of the vessel, among others. The introduced model implementation can be more reusable and understandable for the general scientific community.

The Atlas of Physiology and Pathophysiology: Web-based multimedia enabled interactive simulations.

The paper is a presentation of the current state of development for the Atlas of Physiology and Pathophysiology (Atlas). Our main aim is to provide a novel interactive multimedia application that can be used for biomedical education where (a) simulations are combined with tutorials and (b) the presentation layer is simplified while the underlying complexity of the model is retained. The development of the Atlas required the cooperation of many professionals including teachers, system analysts, artists, and programmers. During the design of the Atlas, tools were developed that allow for component-based creation of simulation models, creation of interactive multimedia and their final coordination into a compact unit based on the given design. The Atlas is a freely available online application, which can help to explain the function of individual physiological systems and the causes and symptoms of their disorders.

[From graphic charts to educational models]. / Od obrázkových schémat k modelum pro výuku.

Thirty five years ago, A.C. Guyton at al. published a description of the large model of physiological relations in a form of a graphic chart. The authors brought this large-scale chart to life using a modern simulation tool--Matlab/Simulink. The original layout, connections and descriptions were saved in the implementation, but contrary to the old system analysis diagram, the new one is also a functional simulation model itself. Thus, the new implementation gives the user the possibility to see and study behaviour of all model's variables in time. Authors also describe the technology of development of multimedia learning simulators.

Evaluation of mitochondrial membrane potential using a computerized device with a tetraphenylphosphonium-selective electrode.

Mitochondrial membrane potential (Deltapsi(m)) plays important roles in the normal function of cells and in pathobiochemical situations. The application of ion-selective electrodes for the measurement of Deltapsi(m) is important for studying normal biological reactions and pathways and mitochondrial diseases. We constructed and optimized a computerized device for real-time monitoring of the Deltapsi(m), which included modification of tetraphenylphosphonium (TPP(+))-selective membrane that improved reproducibility of the TPP(+)-selective electrode. Application of MATLAB software increased the sensitivity of the system. We tested our improved device for membrane potential measurements of isolated mitochondria (in absolute scale of millivolts). In addition, we assessed relative changes of Deltapsi(m) (as changes in TPP(+) concentration) of digitonin-permeabilized cells (hepatocytes, control transmitochondrial cybrids, HeLa G and BSC-40) after addition of substrates, inhibitors, and uncoupler of respiratory chain. Our system can be successfully used for studies of many aspects of the regulation of mitochondrial bioenergetics and as a diagnostic tool for mitochondrial oxidative phosphorylation disorders.

Spike encoding mechanisms in the sound localization pathway.

Two distinct neural circuits calculate the direction of incoming sound in mammals. Lower frequency sounds are processed in the medial superior olive (MSO) and higher frequencies are processed in the lateral superior olive (LSO); together they constitute the superior olivary complex. We show that the spike generation mechanisms of coincidence detection (CD) are employed in both these branches of sound localization pathway. Our description uses the concepts of probabilistic spike generation and spike timing jitter. We explain the notch in sound localization sensitivity described in human psychophysics. We estimate the processing time in the superior olivary complex and discuss possible spike processing mechanisms. Among them, we distinguish between the excitatory coincidence detection (ECD) and the inhibitory coincidence detection (ICD). We compare the latter to the mechanism of firing rate subtraction traditionally attributed to the lateral superior olive.