BACKGROUND: Alzheimer's disease is one of the most common mental illnesses. It is posited that more than 25% of the population is affected by some mental disease during their lifetime. Treatment of each patient draws resources from the economy concerned. Therefore, it is important to quantify the potential economic impact. METHODS: Agent-based, system dynamics and numerical approaches to dynamic modeling of the population of the European Union and its patients with Alzheimer's disease are presented in this article. Simulations, their characteristics, and the results from different modeling tools are compared. RESULTS: The results of these approaches are compared with EU population growth predictions from the statistical office of the EU by Eurostat. The methodology of a creation of the models is described and all three modeling approaches are compared. The suitability of each modeling approach for the population modeling is discussed. CONCLUSION: In this case study, all three approaches gave us the results corresponding with the EU population prediction. Moreover, we were able to predict the number of patients with AD and, based on the modeling method, we were also able to monitor different characteristics of the population.

• MeSH
• Alzheimerova nemoc diagnóza   epidemiologie   MeSH
• biologické modely MeSH
• lidé MeSH
• systémová analýza * MeSH
• teoretické modely * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Our purpose is to assess epidemiological agent-based models-or ABMs-of the SARS-CoV-2 pandemic methodologically. The rapid spread of the outbreak requires fast-paced decision-making regarding mitigation measures. However, the evidence for the efficacy of non-pharmaceutical interventions such as imposed social distancing and school or workplace closures is scarce: few observational studies use quasi-experimental research designs, and conducting randomized controlled trials seems infeasible. Additionally, evidence from the previous coronavirus outbreaks of SARS and MERS lacks external validity, given the significant differences in contagiousness of those pathogens relative to SARS-CoV-2. To address the pressing policy questions that have emerged as a result of COVID-19, epidemiologists have produced numerous models that range from simple compartmental models to highly advanced agent-based models. These models have been criticized for involving simplifications and lacking empirical support for their assumptions. METHODS: To address these voices and methodologically appraise epidemiological ABMs, we consider AceMod (the model of the COVID-19 epidemic in Australia) as a case study of the modelling practice. RESULTS: Our example shows that, although epidemiological ABMs involve simplifications of various sorts, the key characteristics of social interactions and the spread of SARS-CoV-2 are represented sufficiently accurately. This is the case because these modellers treat empirical results as inputs for constructing modelling assumptions and rules that the agents follow; and they use calibration to assert the adequacy to benchmark variables. CONCLUSIONS: Given this, we claim that the best epidemiological ABMs are models of actual mechanisms and deliver both mechanistic and difference-making evidence. Consequently, they may also adequately describe the effects of possible interventions. Finally, we discuss the limitations of ABMs and put forward policy recommendations.

• MeSH
• Betacoronavirus MeSH
• COVID-19 MeSH
• koronavirové infekce epidemiologie   MeSH
• lidé MeSH
• pandemie MeSH
• SARS-CoV-2 MeSH
• statistické modely * MeSH
• systémová analýza * MeSH
• virová pneumonie epidemiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Agent-based models (ABMs) are one of the main sources of evidence for decisions regarding mitigation and suppression measures against the spread of SARS-CoV-2. These models have not been previously included in the hierarchy of evidence put forth by the evidence-based medicine movement, which prioritizes those research methods that deliver results less susceptible to the risk of confounding. We point out the need to assess the quality of evidence delivered by ABMs and ask the question of what is the risk that assumptions entertained in ABMs do not include all the key factors and make model predictions susceptible to the problem of confounding.

• MeSH
• COVID-19 epidemiologie   MeSH
• lidé MeSH
• pandemie * MeSH
• SARS-CoV-2 fyziologie   MeSH
• systémová analýza * MeSH
• teoretické modely MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Multi-criteria decision-making (MCDM) can be formally implemented by various methods. This study compares suitability of four selected MCDM methods, namely WPM, TOPSIS, VIKOR, and PROMETHEE, for future applications in agent-based computational economic (ACE) models of larger scale (i.e., over 10 000 agents in one geographical region). These four MCDM methods were selected according to their appropriateness for computational processing in ACE applications. Tests of the selected methods were conducted on four hardware configurations. For each method, 100 tests were performed, which represented one testing iteration. With four testing iterations conducted on each hardware setting and separated testing of all configurations with the-server parameter de/activated, altogether, 12800 data points were collected and consequently analyzed. An illustrational decision-making scenario was used which allows the mutual comparison of all of the selected decision making methods. Our test results suggest that although all methods are convenient and can be used in practice, the VIKOR method accomplished the tests with the best results and thus can be recommended as the most suitable for simulations of large-scale agent-based models.

• MeSH
• ekonomické modely MeSH
• lidé MeSH
• metody pro podporu rozhodování MeSH
• rozhodování * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Využití znalostí ve formě postupů, konkrétně organizačních procesů a formalizovaných lékařských doporučení, může být vhodné pro vytvoření znalostní báze systému pro podporu v rozhodování (DSS) v oblasti poskytování zdravotní péče. Problém nastává v případě, že pro vývoj DSS chceme použít multiagentní přístup z důvodu rozdílů mezi formalizací chováním se agentů a procesním zápisem. V tomto příspěvku pokračujeme v práci na nové multiagentní architektuře a představíme její integraci do stávajícího systému na podporu v rozhodování (K4Care) v oblasti domácí péče. Základní metodou byla analýza dostupné dokumentace ke komplexnímu systému K4Care, na jejímž základě jsme identifikovali společná místa v rámci již existující funkcionality a návrhu nové architektury. Ta dále posloužila jako výchozí body pro vylepšení modelu K4Care s ohledem na novou multiagentní architekturu založenou na procesech. Analýza potvrdila nejen možnost takové integrace, ale také její přímočarost a minimum nutných změn v modelu K4Care díky dostatečně obecnému návrhu multiagentní architektury založené na procesech. Na základě integrace byly identifikovány okamžité vylepšení podporující lidského experta při jeho práci se systémem, jakož i možnosti dalšího rozšíření systému K4Care na základě této integrace. Integrace multiagentní architektury může být přínosná i pro stávající systémy pro podporu v rozhodování a díky ní otevře nové možnosti založené na multiagentním přístupu.

Utilization of procedural knowledge in the form of organizational processes and formalized medical guidelines can be useful in decision support systems (DSSs) in health care domain. The problem of using this form of knowledge arises when a multi-agent paradigm is to be applied in a DSS due to differences in specification of behavioural models of agents and process formalisms. In this work we continue in enhancing a novel process-based multi-agent architecture and demonstrate its integration into an existing DSS (K4care) focused on home care. We analysed available documentation of the complex system K4Care and identified possible mutual common functionalities of implemented multi-agent system with the new architecture. These were the entry points, using which we further enhanced the K4Care platform with respect to the process-based multi-agent architecture. The analysis proved that the integration is not only possible, but thanks to the general design of the process-based multi-agent architecture can be done with only small changes in the existing K4Care model. Immediate improvements in supporting human experts were identified and possible further improvements of the system were discussed. Adopting the process-based multi-agent architecture can be beneficial even for existing DSSs and can open new possible features emerging from the multi-agent paradigm.

• Klíčová slova
• multiagentní systémy, multiagentní architektury, organizační procesy, formalizované lékařské doporučení, zdravotní péče, domácí péče K4Care,
• MeSH
• financování organizované MeSH
• lidé MeSH
• metody pro podporu rozhodování MeSH
• služby domácí péče MeSH
• software MeSH
• systémy podporující rozhodování v léčbě využití   MeSH
• systémy pro podporu klinického rozhodování využití   MeSH
• zajištění kvality zdravotní péče metody   MeSH
• Check Tag
• lidé MeSH

BACKGROUND: Based on the randomised Euro-EWING99-R1 trial, vincristine, adriamycin, cyclophosphamide (VAC) may be able to replace vincristine, adriamycin, ifosfamide (VAI) in the treatment of standard-risk Ewing sarcoma. However some heterogeneity of treatment effect by gender was observed. The current exploratory study aimed at investigating the influence of gender on treatment efficacy and acute toxicity. PATIENTS AND METHODS: Impact of gender on event-free survival (EFS), acute toxicity by course, switches between treatment arms and cumulative dose of alkylating agents was evaluated in multivariable models adjusted for age including terms to test for heterogeneity of treatment effect by gender. The analysis of the EFS was performed on the intention-to-treat population. RESULTS: EFS did not significantly differ between the 509 males and 347 females (p=0.33), but an interaction in terms of efficacy was suspected between treatment and gender (p=0.058): VAC was associated with poorer EFS than VAI in males, hazard ratio (HR) (VAC/VAI)=1.37 [95% confidence interval (CI), 0.98-1.90], contrasting with HR=0.81 [95%CI, 0.53-1.24] in females. Severe toxicity was more frequent in females, whatever the toxicity type. Thirty patients switched from VAI to VAC (9/251 males, 4%, and 21/174 females, 12%) mostly due to renal toxicity, and three from VAC to VAI (2/258 males, 0.8%, and 1/173 females, 0.6%). A reduction of alkylating agent cumulative dose >20% was more frequent in females (15% versus 9%, p=0.005), with no major difference between VAC and VAI (10% versus 13%, p=0.15). CONCLUSION: Differences of acute toxicity rate and cumulative doses of alkylating agents could not explain the marginal interaction observed in the Euro-EWING99-R1 trial data. Effects of gender-dependent polymorphism/activity of metabolic enzymes (e.g. known for CYP2B6) of ifosfamide versus cyclophosphamide should be explored. External data are required to further evaluate whether there is heterogeneity of alkylating agent effect by gender. TRIAL NUMBERS: NCT00987636 and EudraCT 2008-003658-13.

• MeSH
• alkylační protinádorové látky aplikace a dávkování   škodlivé účinky   MeSH
• časové faktory MeSH
• cyklofosfamid aplikace a dávkování   MeSH
• disparity zdravotního stavu MeSH
• doxorubicin aplikace a dávkování   MeSH
• Ewingův sarkom farmakoterapie   patologie   MeSH
• ifosfamid aplikace a dávkování   MeSH
• lidé MeSH
• mladiství MeSH
• nádory kostí farmakoterapie   patologie   MeSH
• náhrada léků MeSH
• přežití bez známek nemoci MeSH
• progrese nemoci MeSH
• proporcionální rizikové modely MeSH
• protokoly protinádorové kombinované chemoterapie aplikace a dávkování   škodlivé účinky   MeSH
• rizikové faktory MeSH
• sexuální faktory MeSH
• vinkristin aplikace a dávkování   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Geografické názvy
• Evropa MeSH

• MeSH
• antipsychotika analýza   terapeutické užití   MeSH
• lidé MeSH
• medicína založená na důkazech statistika a číselné údaje   MeSH
• odmítnutí účasti etika   psychologie   statistika a číselné údaje   MeSH
• placebo efekt MeSH
• schizofrenie farmakoterapie   MeSH
• statistické modely MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• klinické zkoušky kontrolované MeSH
• klinické zkoušky MeSH

• MeSH
• pravděpodobnost MeSH
• systémová analýza MeSH
• teoretické modely MeSH
• výuka - hodnocení MeSH

INTRODUCTION: Progressing myelodysplastic syndrome (MDS) into acute myeloid leukemia (AML) is an indication for hypomethylating therapy (HMA, 5-Azacytidine (AZA)) and a BCL2 inhibitor (Venetoclax, VEN) for intensive chemotherapy ineligible patients. Mouse models that engraft primary AML samples may further advance VEN + AZA resistance research. METHODS: We generated a set of transplantable murine PDX models from MDS/AML patients who developed resistance to VEN + AZA and compared the differences in hematopoiesis of the PDX models with primary bone marrow samples at the genetic level. PDX were created in NSGS mice via intraosseal injection of luciferase-encoding Lentivirus-infected MDS/AML primary cells from patient bone marrow. We validated the resistance of PDX-leukemia to VEN and AZA and further tested candidate agents that inhibit the growth of VEN/AZA-resistant AML. RESULTS AND DISCUSSION: Transplantable PDX models for MDS/AML arise with 31 % frequency. The lower frequency of transplantable PDX models is not related to peritransplant lethality of the graft, but rather to the loss of the ability of short-term proliferation of leukemic progenitors after 10 weeks of engraftment. There exist subtle genetic and cytological changes between primary and PDX-AML samples however, the PDX models retain therapy resistance observed in patients. Based on in vitro testing and in vivo validation in PDX models, Panobinostat and Dinaciclib are very promising candidate agents that overcome dual VEN + AZA resistance.

• Publikační typ
• časopisecké články MeSH

The P2X4 receptor (P2X4R) is a member of a family of purinergic channels activated by extracellular ATP through three orthosteric binding sites and allosterically regulated by ivermectin (IVM), a broad-spectrum antiparasitic agent. Treatment with IVM increases the efficacy of ATP to activate P2X4R, slows both receptor desensitization during sustained ATP application and receptor deactivation after ATP washout, and makes the receptor pore permeable to NMDG+, a large organic cation. Previously, we developed a Markov model based on the presence of one IVM binding site, which described some effects of IVM on rat P2X4R. Here we present two novel models, both with three IVM binding sites. The simpler one-layer model can reproduce many of the observed time series of evoked currents, but does not capture well the short time scales of activation, desensitization, and deactivation. A more complex two-layer model can reproduce the transient changes in desensitization observed upon IVM application, the significant increase in ATP-induced current amplitudes at low IVM concentrations, and the modest increase in the unitary conductance. In addition, the two-layer model suggests that this receptor can exist in a deeply inactivated state, not responsive to ATP, and that its desensitization rate can be altered by each of the three IVM binding sites. In summary, this study provides a detailed analysis of P2X4R kinetics and elucidates the orthosteric and allosteric mechanisms regulating its channel gating.

• MeSH
• adenosintrifosfát metabolismus   MeSH
• algoritmy MeSH
• gating iontového kanálu účinky léků   fyziologie   MeSH
• HEK293 buňky MeSH
• ivermektin metabolismus   MeSH
• lidé MeSH
• Markovovy řetězce MeSH
• metoda terčíkového zámku MeSH
• purinergní receptory P2X4 účinky léků   metabolismus   fyziologie   MeSH
• vazebná místa MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH