Architectural design of national evidence based medicine information system based on electronic health record.

Background: The global implementation of Electronic Health Records has significantly enhanced the quality of medical care and the overall delivery of public health services. The incorporation of Evidence-Based Medicine offers numerous benefits and enhances the efficacy of decision-making in areas such as prevention, prognosis, diagnosis, and therapeutic approaches.

Objective: The objective of this paper is to propose an architectural design of an Evidence-Based Medicine information system based on the Electronic Health Record, taking into account the existing and future level of interoperability of health information systems in Greece.

A minimal model for gene expression dynamics of bacterial type II toxin-antitoxin systems.

Toxin-antitoxin (TA) modules are part of most bacteria's regulatory machinery for stress responses and general aspects of their physiology. Due to the interplay of a long-lived toxin with a short-lived antitoxin, TA modules have also become systems of interest for mathematical modelling. Here we resort to previous modelling efforts and extract from these a minimal model of type II TA system dynamics on a timescale of hours, which can be used to describe time courses derived from gene expression data of TA pairs.

A fractal kinetics SI model can explain the dynamics of COVID-19 epidemics.

The COVID-19 pandemic has already had a shocking impact on the lives of everybody on the planet. Here, we present a modification of the classical SI model, the Fractal Kinetics SI model which is in excellent agreement with the disease outbreak data available from the World Health Organization. The fractal kinetic approach that we propose here originates from chemical kinetics and has successfully been used in the past to describe reaction dynamics when imperfect mixing and segregation of the reactants is important and affects the dynamics of the reaction.

Chromosomal origin of replication coordinates logically distinct types of bacterial genetic regulation.

For a long time it has been hypothesized that bacterial gene regulation involves an intricate interplay of the transcriptional regulatory network (TRN) and the spatial organization of genes in the chromosome. Here we explore this hypothesis both on a structural and on a functional level. On the structural level, we study the TRN as a spatially embedded network.

Monte Carlo simulations in drug release.

We present methods based on simple sampling Monte Carlo simulations that are used in the study of controlled drug release from devices of various shapes and characteristics. The manuscript is part of a special tribute issue for Prof. Panos Macheras and we have chosen applications of the Monte Carlo method in the field of drug release that were pioneered by him and his research group.

The E. coli transcriptional regulatory network and its spatial embedding.

Usually complex networks are studied as graphs consisting of nodes whose spatial arrangement is of no significance. Several real biological networks are, however, embedded in space. In this paper we study the transcription regulatory network (TRN) of E.

On the unphysical hypotheses in pharmacokinetics and oral drug absorption: Time to utilize instantaneous rate coefficients instead of rate constants.

This work aims to explore the unphysical assumptions associated with i) the homogeneity of the well mixed compartments of pharmacokinetics and ii) the diffusion limited model of drug dissolution. To this end, we i) tested the homogeneity hypothesis using Monte Carlo simulations for a reaction and a diffusional process that take place in Euclidean and fractal media, ii) re-considered the flip-flop kinetics assuming that the absorption rate for a one-compartment model is governed by an instantaneous rate coefficient instead of a rate constant, and, iii) re-considered the extent of drug absorption as a function of dose using an in vivo reaction limited model of drug dissolution with integer and non-integer stoichiometry values. We found that drug diffusional processes and reactions are slowed down in heterogeneous media and the environmental heterogeneity leads to increased fluctuations of the measurable quantities.

On the dilemma of fractal or fractional kinetics in drug release studies: A comparison between Weibull and Mittag-Leffler functions.

We compare two of the most successful models for the description and analysis of drug release data. The fractal kinetics approach leading to release profiles described by a Weibull function and the fractional kinetics approach leading to release profiles described by a Mittag-Leffler function. We used Monte Carlo simulations to generate artificial release data from euclidean and fractal substrates.

Explosive site percolation and finite-size hysteresis.

We report the critical point for site percolation for the "explosive" type for two-dimensional square lattices using Monte Carlo simulations and compare it to the classical well-known percolation. We use similar algorithms as have been recently reported for bond percolation and networks. We calculate the explosive site percolation threshold as p(c) = 0.

Monte Carlo simulations and fractional kinetics considerations for the Higuchi equation.

We highlight some physical and mathematical aspects relevant to the derivation and use of the Higuchi equation. More specifically, the application of the Higuchi equation to different geometries is discussed and Monte Carlo simulations to verify the validity of Higuchi law in one and two dimensions, as well as the derivation of the Higuchi equation under alternative boundary conditions making use of fractional calculus, are presented.

Monte Carlo simulations of drug release from matrices with periodic layers of high and low diffusivity.

We have studied drug release from matrices with periodic layers of high and low diffusivity using Monte Carlo simulations. Despite the fact, that the differential equations relevant to this process have a form that is quite different from the classical diffusion equation with constant diffusion coefficient, we have found that the Weibull model continues to describe the release process as well as in the case of the "classical" diffusion controlled drug release. We examine the similarities and differences between release from matrices with periodic layers and matrices with random mixtures of high and low diffusivity area and show that the periodic geometrical arrangement of the low diffusivity areas has an influence in the release profile which is negligible for low diffusivity ratios, but becomes important in the case of high diffusivity ratios and for intermediate values of the periodic "length".

Monte Carlo simulations for the study of drug release from matrices with high and low diffusivity areas.

We use Monte Carlo simulations in order to study diffusion controlled drug release from matrices consisting of random mixtures of high and low diffusivity areas (random mixing), and from matrices covered by a thin film of low diffusivity (ordered mixing). We compared our results with the Weibull model for drug release and found that it provides an adequate description of the release process in all cases of random mixing and most cases of ordered mixing. We have studied the dependence of the Weibull parameters on the diffusion coefficient and, in most cases, found a rather simple linear dependence.

On the use of the Weibull function for the discernment of drug release mechanisms.

Previous findings from our group based on Monte Carlo simulations indicated that Fickian drug release from Euclidian or fractal matrices can be described with the Weibull function. In this study, the entire drug release kinetics of various published data and experimental data from commercial or prepared controlled release formulations of diltiazem and diclofenac are analyzed using the Weibull function. The exponent of time b of the Weibull function is linearly related to the exponent n of the power law derived from the analysis of the first 60% of the release curves.

Modeling and Monte Carlo simulations in oral drug absorption.

Drug dissolution, release and uptake are the principal components of oral drug absorption. All these processes take place in the complex milieu of the gastrointestinal tract and they are influenced by physiological (e.g.

Michaelis-Menten kinetics under spatially constrained conditions: application to mibefradil pharmacokinetics.

Two different approaches were used to study the kinetics of the enzymatic reaction under heterogeneous conditions to interpret the unusual nonlinear pharmacokinetics of mibefradil. Firstly, a detailed model based on the kinetic differential equations is proposed to study the enzymatic reaction under spatial constraints and in vivo conditions. Secondly, Monte Carlo simulations of the enzyme reaction in a two-dimensional square lattice, placing special emphasis on the input and output of the substrate were applied to mimic in vivo conditions.

A reappraisal of drug release laws using Monte Carlo simulations: the prevalence of the Weibull function.

Purpose: To verify the Higuchi law and study the drug release from cylindrical and spherical matrices by means of Monte Carlo computer simulation.

Method: A one-dimensional matrix, based on the theoretical assumptions of the derivation of the Higuchi law, was simulated and its time evolution was monitored. Cylindrical and spherical three-dimensional lattices were simulated with sites at the boundary of the lattice having been denoted as leak sites.

Analysis of Case II drug transport with radial and axial release from cylinders.

Analysis is presented for Case II drug transport with axial and radial release from cylinders. The previously reported [J. Control Release 5 (1987) 37] relationships for radial release from films and slabs are special cases of the general solution derived in this study.