Discrete-Event Simulation Modeling in Healthcare: A Comprehensive Review.

Discrete-event simulation (DES) is a stochastic modeling approach widely used to address dynamic and complex systems, such as healthcare. In this review, academic databases were systematically searched to identify 231 papers focused on DES modeling in healthcare. These studies were sorted by year, approach, healthcare setting, outcome, provenance, and software use. Among the surveys, conceptual/theoretical studies, reviews, and case studies, it was found that almost two-thirds of the theoretical articles discuss models that include DES along with other analytical techniques, such as optimization and lean/six sigma, and one-third of the applications were carried out in more than one healthcare setting, with emergency departments being the most popular. Moreover, half of the applications seek to improve time- and efficiency-related metrics, and one-third of all papers use hybrid models. Finally, the most popular DES software is Arena and Simul8. Overall, there is an increasing trend towards using DES in healthcare to address issues at an operational level, yet less than 10% of DES applications present actual implementations following the modeling stage. Thus, future research should focus on the implementation of the models to assess their impact on healthcare processes, patients, and, possibly, their clinical value. Other areas are DES studies that emphasize their methodological formulation, as well as the development of frameworks for hybrid models.

Adhesive Resins with High Shelf-Life Stability Based on Tetra Unsaturated Monomers with Tertiary Amines Moieties.

This work reports the use of two monomers with two tertiary amines and four methacrylic (TTME) or acrylic (TTAC) terminal groups as co-initiators in the formulation of experimental resin adhesive systems. Both monomers were characterized by FT-IR and 1H NMR spectroscopies. The control adhesive was formulated with BisGMA, TEGDMA, HEMA, and the binary system CQ-EDAB as a photo-initiator system. For the experimental adhesives, the EDAB was completely replaced for the TTME or the TTAC monomers. The adhesives formulated with TTME or TTAC monomers achieved double bond conversion values close to 75%. Regarding the polymerization rate, materials formulated with TTME or TTAC achieved lower values than the material formulated with EDAB, giving them high shelf-life stability. The degree of conversion after shelf simulation was only reduced for the EDAB material. Ultimate tensile strength, translucency parameter, and micro-tensile bond strength to dentin were similar for control and experimental adhesive resins. Due to their characteristics, TTME and TTAC monomers are potentially useful in the formulation of photopolymerizable resins for dental use with high shelf-life stability.

Presentación de una paciente con síndrome de Stevens-Johnson y necrólisis epidérmica tóxica / Presentation of a patient with stevens-johnson syndrome / toxic epidermal necrolysis

Se presentó una paciente femenina escolar de seis años de edad raza mestiza, con antecedentes de salud, sin antecedentes familiares a destacar; embarazo y parto normales, a término, sin patología perinatal, correctamente alimentada, bien inmunizada; buen crecimiento y desarrollo. Controlada por el pediatra, que acudió a su médico de familia por presentar síntomas catarrales (tos pertinaz y fiebre) recibió medicación con fenitoina y al segundo día de tratamiento comienza con manifestaciones cutáneas de ampollas que se destechan y dejan observar zonas eritematosas y húmedas que se extendieron a casi la totalidad de la superficie corporal. El síndrome de Stevens-Johnson es una dermatosis potencialmente fatal caracterizada por una extensanecrosis epidérmica y de mucosas que se acompaña de ataque al estado general. Este síndrome y la necrólisis epidérmica tóxica son reacciones de hipersensibilidad que se consideran formas polares clínico-patológicas de una misma enfermedad. Ambas son reacciones adversas cutáneas severas relacionadas con varios medicamentos. Estas enfermedades tienen impacto significante en la salud pública debido a su alta morbilidad y mortalidad. El porcentaje de superficie cutánea afectada es pronóstico y clasifica a esta dermatosis en tres grupos: síndrome Stevens Johnson (cuando afecta menos de 10 % de superficie corporal) superposición síndrome Stevens Johnson - necrólisis epidérmica tóxica (del 10 al 30 %) y necrólisis epidérmica tóxica (despegamiento cutáneo mayor al 30 %).

Six years old, mixed race school girl patient, with a health record, no family history to note, was presented. Born from a normal pregnancy and a delivery at term. Properly fed, well immunized. Good growth and development. The patient had come to her family physician because of cold symptoms with persistent cough and fever; she received a medication with phenytoin among other drugs. On the second day of treatment the patient developed cutaneous manifestations of blisters that exposed, when opened, erythematous and humid areas that extended to almost the entire body surface. The Stevens - Johnson syndrome is a potentially fatal skin disease characterized by extensive epidermal and mucosal necrosis that is accompanied by malaise. Stevens Johnson Syndrome and toxic epidermal necrolysis are hypersensitivity reactions that are considered clinic and pathologic entity of the same polar forms. Both Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are severe cutaneous adverse reactions associated with some medications (RACS). These conditions have significant impact on public health because of its high morbidity and mortality. The percentage of affected skin surface classifies this disease into three groups and could define the prognosis: -SSJ, when it affects less than 10% body surface - Overlapping SSJ-NET of 10-30% - NET, greater than 30% skin detachment.

Variation in the composition and in vitro proinflammatory effect of urban particulate matter from different sites.

Spatial variation in particulate matter-related health and toxicological outcomes is partly due to its composition. We studied spatial variability in particle composition and induced cellular responses in Mexico City to complement an ongoing epidemiologic study. We measured elements, endotoxins, and polycyclic aromatic hydrocarbons in two particle size fractions collected in five sites. We compared the in vitro proinflammatory response of J774A.1 and THP-1 cells after exposure to particles, measuring subsequent TNFα and IL-6 secretion. Particle composition varied by site and size. Particle constituents were subjected to principal component analysis, identifying three components: C(1) (Si, Sr, Mg, Ca, Al, Fe, Mn, endotoxin), C(2) (polycyclic aromatic hydrocarbons), and C(3) (Zn, S, Sb, Ni, Cu, Pb). Induced TNFα levels were higher and more heterogeneous than IL-6 levels. Cytokines produced by both cell lines only correlated with C(1) , suggesting that constituents associated with soil induced the inflammatory response and explain observed spatial differences.

The oxidative potential and biological effects induced by PM10 obtained in Mexico City and at a receptor site during the MILAGRO Campaign.

As part of a field campaign that studied the impact of Mexico City pollution plume at the local, sub-regional and regional levels, we studied transport-related changes in PM(10) composition, oxidative potential and in vitro toxicological patterns (hemolysis, DNA degradation). We collected PM(10) in Mexico City (T(0)) and at a suburban-receptor site (T(1)), pooled according to two observed ventilation patterns (T(0) → T(1) influence and non-influence). T(0) samples contained more Cu, Zn, and carbon whereas; T(1) samples contained more of Al, Si, P, S, and K (p < 0.05). Only SO(4)(-2) increased in T(1) during the influence periods. Oxidative potential correlated with Cu/Zn content (r = 0.74; p < 0.05) but not with biological effects. T(1) PM(10) induced greater hemolysis and T(0) PM(10) induced greater DNA degradation. Influence/non-influence did not affect oxidative potential nor biological effects. Results indicate that ventilation patterns had little effect on intrinsic PM(10) composition and toxicological potential, which suggests a significant involvement of local sources.

In vitro biological effects of airborne PM2.5 and PM10 from a semi-desert city on the Mexico-US border.

Compelling evidence indicates that exposure to urban airborne particulate matter (PM) affects health. However, how PM components interact with PM-size to cause adverse health effects needs elucidation, especially when considering soil and anthropogenic sources. We studied PM from Mexicali, Mexico, where soil particles contribute importantly to air pollution, expecting to differentiate in vitro effects related to PM-size and composition. PM samples with mean aerodynamic diameters ≤2.5µm (PM(2.5)) and ≤10µm (PM(10)) were collected in Mexicali (October 2005-March 2006) from a semi-urban (expected larger participation of soil sources) and an urban (predominately combustion sources) site. Samples were pooled by site and size, analyzed for elemental composition (particle-induced X-ray emission) and tested in vitro for: induction of human erythrocytes membrane disruption (hemolysis) (colorimetrically); inhibition of cell proliferation (ICP) (crystal violet) and TNFα/IL-6 secretion (ELISA) using J774.A1 murine monocytic cells; and DNA degradation using Balb/c3T3 cell naked DNA (electrophoretically). Results of PM elemental composition principal component analysis were used in associating cellular effects. Sixteen elements identified in PM grouped in two principal components: Component(1) (C(1)): Mg, Al, Si, P, Cl, K, Ca, Ti, V, Cr, Fe, and Component(2) (C(2)): Cu, Zn. Hemolysis was predominately induced by semi-urban-PM(10) (p<0.05) and was associated with urban-PM(10)C(1) (r=0.62, p=0.003). Major ICP resulted with semi-urban PM(2.5) (p<0.05). TNFα was mainly induced by urban samples regardless of size (p<0.05) and associated with urban-PM(2.5)C(2) (r=0.48, p=0.02). Both PM(10) samples induced highest DNA degradation (p<0.05), regardless of location. We conclude that PM-size and PM-related soil or anthropogenic elements trigger specific biological-response patterns.

Relations between PM10 composition and cell toxicity: a multivariate and graphical approach.

Previous studies have used particle mass and size as metrics to link airborne particles with deleterious health effects. Recent evidence suggests that particle composition can play an important role in PM-toxicity; however, little is known about the specific participation of components (individually or acting in groups) present in such a complex mixture that accounts for toxicity. This work explores relationships among PM(10) components in order to identify their covariant structure and how they vary in three sites in Mexico City. Relationships between PM(10) with cell toxicity and geographical location were also explored. PM(10) was analyzed for elemental composition, organic and elemental carbon, endotoxins and the induction of inhibition of cell proliferation, IL-6, TNFalpha and p53. PM(10) variables were evaluated with principal component analysis and one-way ANOVA. The inhibition of cell proliferation, IL-6 and TNFalpha were evaluated with factorial ANOVA and p53 with the Welch test. The results indicate that there is heterogeneity in particle mass, composition and toxicity in samples collected at different sites. Multivariate analysis identified three major groups: (1) S/K/Ca/Ti/Mn/Fe/Zn/Pb; (2) Cl/Cr/Ni/Cu; and (3) endotoxins, organic and elemental carbon. Groups 1 and 3 showed significant differences among sites. Factorial ANOVA modeling indicated that cell proliferation was affected by PM concentration; TNFalpha and IL-6 by the interaction of concentration and site, and p53 was different by site. Radial plots suggest the existence of complex interactions between components, resulting in characteristic patterns of toxicity by site. We conclude that interactions of PM(10) components determine specific cellular outcomes.