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System dynamics is a computer-based approach for analyzing and designing complex systems over time. In this study the cognitive casualty map was developed to make a concept about the system then the stock-flow model was set up based on the market demand and supply concept.
The model demonstrates the interdependencies between the NDP variables through four cognitive maps. Some issues in availability, willingness to pay, rational use and quality of medicines are pointed in the model. The stock-flow diagram shows how the demand for a medicine is formed and how it is responded through NDP objectives. The effects of changing variables on the other NDP variables can be studied after running the stock-flow model.
In fact SD models are crucial and effective tools for focusing on stock variables and the flows between them. Therefore, it seems using SD as a well-adjusted modeling technique is authentic to respond to the requirements of this study [14, 15].
In Iran, there are two different governmental approaches against imported medicines and domestically produced ones, therefore it was tried to consider these two approaches in studying the main NDP variables. The nature of the model leads to study it in two parts; the conceptual cognitive map was explored in part 1 and quantifying the variables and running their relationships are explained in part 2 in a stock-flow model.
The stock-flow model has been set based on the demand and supply concept. This demand was made by the population structure and incidence rates. We had to break the population to four stock variables due to the population structure of Iran. Because of the lack of disease epidemiology data in Iran we used any data from any country for covering incidence rates. It was thought this lack of data could be covered by the ability that is in SD to do a wide range of sensitivity analysis. The supply side was summarized to a few level and auxiliary variables that comes to the model as input variables, then it can be expanded to more detailed models in supplementary studies.
Availability subsystem consists of the supply side of the stock-flow model and number of pharmacies as the constant variable; although increasing the number of pharmacies can improve the availability, it cannot overwhelm the total stock situation; the total stock of the modeled medicine comes from the total demand through domestically production and imports. The number of pharmacies under the control of the government has a slow growth due to low population growth rate.
The insurance system and subsidization that play the main role in affordability subsystem present themselves as two constant variables in the stock-flow diagram. The role of insurance organizations can be explained based on the other variables in health financial system. There is a stock variable in the model that shows the cumulative medication costs of the illness and demonstrates the time when patients could fall in catastrophic expenses. The model shows only cancer and autoimmune patients can fall in the catastrophic expenses; medication for normal high burden diseases including cardiovascular, diabetes, central nervous disorders and gastro intestinal are too cheap to send patients to financial failure.
AA plan the project, set up the panels, developed the primary models, data analysis and drafted the paper, AK and RD conceived and revised the model and supervised the project, MA gave consultation on the study design and edited the draft, AC gave consultation on the conceptual model, SN revised the conceptual model and gave consultation on the medication procedures, MJ revised the stock-flow model and data analysis. All authors read and approved the final manuscript.
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Cognitive impairment responses are important research topics in the study of degenerative brain diseases as well as in understanding of human mental activities. To compare response to scopolamine (SPL)-induced cognitive impairment, we measured altered parameters for learning and memory ability, inflammatory response, oxidative stress, cholinergic dysfunction and neuronal cell damages, in Korl:ICR stock and two commercial breeder stocks (A:ICR and B:ICR) after relevant SPL exposure. In the water maze test, Korl:ICR showed no significant difference in SPL-induced learning and memory impairment compared to the two different ICRs, although escape latency was increased after SPL exposure. Although behavioral assessment using the manual avoidance test revealed reduced latency in all ICR mice after SPL treatment as compared to Vehicle, no differences were observed between the three ICR stocks. To determine cholinergic dysfunction induction by SPL exposure, activity of acetylcholinesterase (AChE) assessed in the three ICR stocks revealed no difference of acetylcholinesterase activity. Furthermore, low levels of superoxide dismutase (SOD) activity and high levels of inflammatory cytokines in SPL-treated group were maintained in all three ICR stocks, although some variations were observed between the SPLtreated groups. Neuronal cell damages induced by SPL showed similar response in all three ICR stocks, as assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, Nissl staining analysis and expression analyses of apoptosis-related proteins. Thus, the results of this study provide strong evidence that Korl:ICR is similar to the other two ICR. Stocks in response to learning and memory capacity.
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