2 research outputs found
Multi Agent Functional Bone Simulation: A theoretical study
In 200 A.D., Galen described bones as the fundamental system of body
protection. Bones are highly dynamic, in constant renovation to preserve their
properties. Understanding bone metabolism has become a relevant area of
research. The most common bone disease is osteoporosis and is characterized by
low bone mass and microarchitecture disturbances. The major consequence of
osteoporosis are fragility fractures (fractures that occur with low impact trauma).
Osteoporosis causes more than 8.9 million fractures each year worldwide.
Several therapies are effective in preventing fractures and treating osteoporosis.
However, there is an enormous difficulty in predicting osteoporosis related
fractures and understanding who needs these therapies in order to prevent bone
loss. In practical clinic, it becomes essential to have a model describing the bone
remodeling process and the impact of the different cellular mediators in the bone
metabolism.
Although some mathematical models already describe the variation of the
bone cells, they do it in a continuous and deterministic way with few cellular
mediators. Many studies and experimental results have shown that cellular
metabolism and birth-and-death processes in population dynamics are
stochastic. Furthermore, mathematical models are reliable on describing a macro
level, whereas multiagent simulation models are used to link micro and macro
perspectives.
In this thesis we have developed a multiagent stochastic model that
simulates a timeline remodeling cycle. Our simulator reproduces the homeostatic
process of remodeling with the different phases of it, which is time consistent
with the real biological process. Our model includes the most relevant cellular
mediators in the bone metabolism. Our model demonstrated to have great
sensibility to predict bone loss caused by some chronic diseases such hyper and
hypoparathyroidism, and excess of glucocorticoids, and also to the most known
causes of osteoporosis: estrogen or vitamin D deficiency. Overall, this model
provides a deeper understanding about bone metabolism and the pathologies
associated with it.Em 200 A.D, Galen descreveu os ossos como o sistema fundamental de
proteção do corpo. Os ossos são estruturas altamente dinâmicas e estão em
constante remodelação para preservarem as suas propriedades. Compreender o
metabolismo do osso tornou-se uma marcante área de pesquisa. A doença óssea
mais comum é a osteoporose que causa mais de 8.9 milhões de fraturas em todo
o mundo. Existem várias terapias eficazes em prevenir e tratar esta doença.
Contudo, existe uma enorme dificuldade em prevê-la, bem como em entender
quem necessita de terapêuticas para a retardar ou evitar a perda óssea. Na prática
clínica, revelou-se importante existir um modelo que descreva o processo de
remodelação óssea assim como o impacto dos diferentes mediadores celulares no
metabolismo ósseo.
Apesar de já existirem alguns modelos matemáticos que descrevem a
variação das células ósseas na remodelação óssea, fazem-no de uma forma
contínua e determinística e com poucos mediadores celulares. Bastantes estudos
e resultados experimentais revelam que o metabolismo celular, bem como os
processos de nascimento e morte em populações dinâmicas, são estocásticos.
Para além disso, os modelos matemáticos são fidedignos em descrever um nível
macro enquanto modelos de simulação de multiagentes são utilizados para
conectar ambas as perspetivas, micro e macro.
O modelo estocástico de multiagentes desenvolvido neste trabalho, simula
um ciclo de remodelação ao longo do tempo. O nosso simulador reproduz o
processo homeostático de remodelação com as diferentes fases deste, o que é
consistente com o processo biológico real. Para além disso, o nosso modelo inclui
os mediadores celulares mais relevantes no metabolismo ósseo. Os resultados do
modelo demonstram ter sensibilidade em prever a perda óssea devido a algumas
doenças crónicas como hiper e hipoparatiroidismo e o excesso de
glucocorticoides, bem como das mais conhecidas causas de osteoporose: a
deficiência de estrogénio e vitamina D. No geral, este modelo permite-nos ter um
maior entendimento do metabolismo ósseo, bem como das patologias associadas
a este
Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries
Background
Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks.
Methods
The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned.
Results
A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31).
Conclusion
Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)