Modeling of Microneedle Arrays in Transdermal Drug Delivery Applications.

The use of computational tools for the development of technologies in fields such as medicine and engineering has facilitated the process of designing new components and devices for these areas. In this work, two proposals focused on a hollow microneedle array (MNA) for the administration of an analgesic drug are shown and evaluated by means of a computational fluid dynamics (CFD) simulation distributed in three stages. In the first stage, the behavior of lidocaine through the MNA was evaluated as a workflow. Then, the possible entry of the drug into the organism, which was established as a porous aqueous medium, was modeled. Finally, a joint simulation was performed to understand the general behavior in the interaction between the outflow of an MNA and the body to which lidocaine is administered. The input parameters to the simulation were set at a velocity of 0.05 m∙s-1, at a pressure of 2000 Pa, the dominant behavior was defined as laminar flow, and a resistive pressure at the inlet of 400 Pa. Our results indicate that the vertical flow exhibits a better fluid distribution across the MNAs and favorable infiltration behavior, representing better delivery of the analgesic to the skin capillaries.

Instrumental piezoeléctrico comparado con sierra convencional en cirugía ortognática / Piezoelectric bone surgery compared to conventional saw in orthognathic surgery

RESUMEN: Introducción: La utilización de instrumental piezoeléctrico en cirugía ortognática ha ido en aumento con el fin de minimizar el riesgo de daño a tejidos blandos en comparación al uso de sierra convencional. Sin embargo, aún existe incertidumbre respecto a las complicaciones asociadas a cada instrumental. Métodos: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un meta análisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. Resultados y conclusiones: Identificamos cuatro revisiones sistemáticas que en conjunto incluyeron 10 estudios primarios, de los cuales, cuatro corresponden a ensayos aleatorizados. Concluimos que el uso de instrumental piezoeléctrico en comparación con la sierra convencional podría disminuir el riesgo de daño nervioso grave y disminuir el sangrado grave (>500 mL), pero la certeza de la evidencia es baja. Por otra parte, el uso de instrumental piezoeléctrico podría presentar poca o nula diferencia en el dolor postoperatorio, pero la certeza de la evidencia es baja. Finalmente no es posible establecer con claridad si el uso de instrumental piezoeléctrico disminuye la pérdida de sangre intraoperatoria (variable continua), la inflamación postoperatoria o el tiempo operatorio, ya que la certeza de la evidencia existente ha sido evaluada como muy baja.

ABSTRACT: Introduction: The use of piezoelectric bone surgery in orthognathic surgery has been increasing to minimize the risk of soft tissue damage compared to conventional saws. However, there is still uncertainty regarding the complications associated with each instrument. Methods: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed primary studies' data, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. Results and conclusions: We identified four systematic reviews that included 10 primary studies, four of which corresponded to randomized trials. We conclude that the use of piezoelectric instrumentation compared to the conventional saw may reduce the risk of severe nerve damage and decrease severe bleeding (>500 mL), but the certainty of the evidence is low. On the other hand, the use of piezoelectric bone surgery may make little or no difference in postoperative pain, but the certainty of the evidence is low. Finally, we are uncertain whether piezoelectric bone surgery reduces intraoperative blood loss (continuous variable), postoperative inflammation, and operative time, as the certainty of the evidence has been assessed as very low.

Instrumental piezoeléctrico en comparación a instrumental rotatorio convencional para la exodoncia de terceros molares mandibulares / Piezoelectric bone surgery versus conventional rotatory system for lower third molar surgery

RESUMEN: Introducción: Tradicionalmente la osteotomía requerida en la exodoncia de terceros molares mandibulares incluidos o semi-incluidos ha sido realizada con instrumental manual o rotatorio. Con el advenimiento de la técnica ultrasónica de la cirugía piezoeléctrica, se hace necesario comparar la seguridad y efectividad de ambas técnicas. Métodos: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. Resultados y conclusiones: Identificamos ocho revisiones sistemáticas que en conjunto incluyeron 22 estudios primarios, de los cuales 12 corresponden a ensayos clínicos aleatorizados. Concluimos que el uso de instrumental piezoeléctrico en comparación con el instrumental rotatorio convencional podría aumentar el tiempo quirúrgico y podría disminuir el dolor temprano y tardío, junto con el edema al día siete, pero la certeza de la evidencia es baja. Por otra parte, el uso de instrumental piezoeléctrico podría resultar en poca o nula diferencia en el desarrollo de alteraciones neurológicas postoperatorias ya que la certeza de la evidencia es baja. Además, el uso de piezoeléctrico probablemente resulte en poca o nula diferencia en la apertura bucal.

ABSTRACT: Introduction: Traditionally, osteotomy techniques required in exodontia of included or semi-included mandibular third molars has been performed with manual or rotary instruments. With the advent of the ultrasonic technique of piezoelectric surgery, it is necessary to evaluate the effectiveness and safety of both osteotomy techniques. Methods: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed primary studies' data, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. Results and conclusions: We identified eight systematic reviews that together included 22 primary studies overall, of which 12 were randomized trials. We conclude that the use of piezoelectric surgery compared with conventional rotary instruments may increase operative time and reduce early and late pain, along with edema at day seven, but the certainty of the evidence is low. On the other hand, the use of piezoelectric instrumentation may result in little or no difference in the development of postoperative neurologic disturbances as the certainty of the evidence is low. Also, piezoelectric use probably makes little or no differences in mouth opening.

Abordaje transconjuntival en comparación con abordaje subciliar para el tratamiento de fracturas orbitarias / Transconjunctival versus subciliary approach for the treatment of orbital fractures

RESUMEN: Introducción: Los abordajes transconjuntival preseptal y subciliar han sido ampliamente utilizados para el manejo quirúrgico de las fracturas orbitarias. Sin embargo, aún existe incertidumbre sobre las complicaciones asociadas a cada uno de estos abordajes. Métodos: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios. Realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. Resultados y conclusiones: Identificamos seis revisiones sistemáticas que en conjunto incluyeron 21 estudios primarios, de los cuales cuatro corresponden a ensayos aleatorizados. Concluimos que el abordaje transconjuntival preseptal podría disminuir tanto la incidencia de ectropión como de un resultado estético insatisfactorio, pero la certeza de la evidencia es baja. Además, este abordaje probablemente disminuye el riesgo de complicaciones intra y postoperatorias, tales como diplopía, parestesia transitoria, equimosis, exposición escleral, laceración del plato tarsal y laceración palpebral inferior. Por otro lado, el abordaje transconjuntival podría aumentar el riesgo de entropión, pero la certeza de la evidencia también es baja.

ABSTRACT: Introduction: The preseptal transconjunctival and subciliary approach have been widely used for the surgical management of orbital fractures. However, there is still uncertainty about the complications associated with each of these approaches. Methods: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. Results and conclusions: We identified six systematic reviews that included 21 primary studies, four of which correspond to randomized trials. We conclude that the preseptal transconjunctival approach could decrease the incidence of ectropion and an unsatisfactory aesthetic result, but the certainty of the evidence is low. Furthermore, this approach probably decreases the risk of intra and postoperative complications, such as diplopia, transient paresthesia, ecchymosis, scleral show, tarsal plate laceration and lower palpebral laceration. On the other hand, the transconjunctival approach could increase the risk of entropion, but the certainty of the evidence is also low.

Nanoparticle Concentration vs Surface Area in the Interaction of Thiol-Containing Molecules: Toward a Rational Nanoarchitectural Design of Hybrid Materials.

The effect of accounting for the total surface in the association of thiol-containing molecules to nanosilver was assessed using isothermal titration calorimetry, along with a new open access algorithm that calculates the total surface area for samples of different polydispersity. Further, we used advanced molecular dynamic calculations to explore the underlying mechanisms for the interaction of the studied molecules in the presence of a nanosilver surface in the form of flat surfaces or as three-dimensional pseudospherical nanostructures. Our data indicate that not only is the total surface area available for binding but also the supramolecular arrangements of the molecules in the near proximity of the nanosilver surface strongly affects the affinity of thiol-containing molecules to nanosilver surfaces.

Uso de HFR-supra para el tratamiento de porfiria cutánea tarda en paciente en hemodiálisis crónica / Use HFR-supra for porphyria cutanea tarda treatment in hemodialysis patient

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NANoPoLC algorithm for correcting nanoparticle concentration by sample polydispersity.

Variability in the polydispersity of colloidal nanoparticles results in significant differences in the total number of nanoparticles available for the determination of their concentration, which ultimately affects their bioavailability and biodistribution. In the current work, we developed a novel algorithm, named Nanoparticle Polydispersity Corrector (NANoPoLC), which was shown to render a more realistic calculation of the actual nanoparticle concentration in solution.

Choice of a Suitable Dosimeter for Photon Percentage Depth Dose Measurements in Flattening Filter-Free Beams.

The International Atomic Energy Agency Technical Reports Series-398 code of practice for dosimetry recommends measuring photon percentage depth dose (PDD) curves with parallel-plate chambers. This code of practice was published before flattening filter-free (FFF) beams were widely used in clinical linear accelerators. The choice of detector for PDD measurements needs to be reassessed for FFF beams given the physical differences between FFF beams and flattened ones. The present study compares PDD curves for FFF beams of nominal energies 6 MV, 6 FFF, 10 MV, and 10 FFF from a Varian TrueBeam linear accelerator (Varian Medical Systems, Palo Alto, USA) acquired with Scanditronix photon diodes, two scanning type chambers (both PTW 31010 Semiflex), two small volume chambers (Wellhofer CC04 and PTW 31016 PinPoint 3D), PTW 34001 Roos, Scanditronix Roos, and NACP 02 parallel-plate chambers. Results show that parallel-plate ion chambers can be used for photon PDD measurements, although for better accuracy, recombination effects should be taken into account.

Association models for binding of molecules to nanostructures.

The interaction between nanoparticles and molecules plays a key role in determining the activity and performance of a given nanostructure. These interactions are pivotal for a variety of applications including drug delivery, surface manipulation for targeted therapies, and catalysis. However, to this day, gathering precise association parameters for the interaction of the molecules with nanostructures remains elusive and mostly imprecise. In this review, we present a critical discussion of the most commonly used techniques and models intended for determining the association of molecules with nanoparticles. Particular emphasis has been put on discussing the limitations and pitfalls related to determining association constants in this tutorial review.

A quality index for equivalent uniform dose.

Equivalent uniform dose (EUD) is the absorbed dose that, when homogeneously given to a tumor, yields the same mean surviving clonogen number as the given non-homogeneous irradiation. EUD is used as an evaluation tool under the assumption that two plans with the same value of EUD are equivalent, and their biological effect on the tumor (clonogen survival) would be the same as the one of a homogeneous irradiation of absorbed dose EUD. In this work, this assumption has been studied, and a figure of merit of its applicability has been obtained. Distributions of surviving clonogen number for homogeneous and non-homogeneous irradiations are found to be different even if their mean values are the same, the figure of merit being greater when there is a wider difference, and the equivalence assumption being less valid. Therefore, EUD can be closer to a uniform dose for some cases than for other ones (high α values, extreme heterogeneity), and the accuracy of the radiobiological indices obtained for evaluation, could be affected. Results show that the equivalence is very sensitive to the choice of radiobiological parameters, and this conclusion has been derived from mathematical properties of EUD.

[Impact of a PET/CT facility in its community environment]. / Impacto en el ámbito comunitario de una instalación de tomografía por emisión de positrones-tomografía computada (PET/CT).

BACKGROUND: The PET/CT (Positron Emission Tomography/Computed Tomography) technique is currently expanding, with new facilities and indications appearing every year. Being mostly an outpatient technique, patients leave the facility when the study has been performed, although they still retain a certain amount of radiopharmaceutical. Therefore, setting up a PET/CT facility might involve a risk increase for the population. This study aims at estimating this risk. METHODS: Comprehensive measurements to estimate dose levels have been carried out in the PET/CT facility at Hospital General Universitario Gregorio Marañón. The population has been distributed into five categories according to their involvement in the studies and their radiation exposure. A quantitative dose estimation has been carried out. RESULTS: The risk associated with a PET/CT facility has been assessed and no risk increase has been detected. Staff dose is shown to be less than 2 µSv per patient, ˜20 µSv for an accompanying person and ˜40 µSv for a relative. Citizens walking along with patients or sharing public transportation with them receive a dose that is below Madrid´s background radiation. CONCLUSIONS: Values obtained are well below annual dose limits. Moreover, these results support the outpatient care of this kind of studies, because accompanying persons´ and relatives´ risk is negligible. The impact of a PET/CT facility does not involve an increase in risk for the general population.

The use of a mixed Poisson model for tumour control probability computation in non homogeneous irradiations.

Tumour control probability (TCP) is the probability of destroying every clonogen in a tumour as a result of a Radiation Therapy treatment. Assuming absorbed dose homogeneity throughout the tumour volume, TCP can be easily derived from a cell survival model. If absorbed dose is non homogeneous, its distribution has to be taken into account, because survival fractions depend on dose. This work presents a method based on mixture probability distributions to introduce absorbed dose heterogeneity using dose volume histograms. Results are close to the ones provided by the standard voxel oriented method usually utilized, but the mixture method makes more robust assumptions about independence between voxels. Therefore, this method is more flexible, and could potentially deal with variations in survival fraction caused by other factors.

A probability approach to the study on uncertainty effects on gamma index evaluations in radiation therapy.

Two datasets of points of known spatial positions and an associated absorbed dose value are often compared for quality assurance purposes in External Beam Radiation Therapy (EBRT). Some problems usually arise regarding the pass fail criterion to accept both datasets as close enough for practical purposes. Instances of this kind of comparisons are fluence or dose checks for intensity modulated radiation therapy, modelling of a treatment unit in a treatment planning system, and so forth. The gamma index is a figure of merit that can be obtained from both datasets; it is widely used, as well as other indices, as part of a comparison procedure. However, it is recognized that false negatives may take place (there are acceptable cases where a certain number of points do not pass the test) due in part to computation and experimental uncertainty. This work utilizes mathematical methods to analyse comparisons, so that uncertainty can be taken into account. Therefore, false rejections due to uncertainty do not take place and there is no need to expand tolerances to take uncertainty into account. The methods provided are based on the rules of uncertainty propagation and help obtain rigorous pass/fail criteria, based on experimental information.

Confidence intervals in dose volume histogram computation.

PURPOSE: Dose volume histograms (DVHs) are used in radiation therapy plan optimization and evaluation. Irradiation strategies are decided at the planning step, and an assessment of the reliability of computed dose distributions and DVHs is needed to ensure that decisions are made based on reliable information. This work describes a method used to assign confidence intervals to DVHs, caused by the uncertainty associated with dose computation. METHODS: A simple mathematical model has been developed, based on several alternative models for point dose uncertainty (rectangular, triangular, and Gaussian probability distributions). The result is an alpha-DVH, to be computed for two a values (0.25/0.75 or 0.10/0.90) to obtain a confidence interval. This method has been applied to several DVH curves. RESULTS: alpha-DVHs are dependent on the point uncertainty probability distribution, on the standard uncertainty, and on the choice of confidence level. Confidence intervals can be assigned either to the volume encompassed by an isodose level or to the dose corresponding to a given volume. CONCLUSIONS: alpha-DVHs provide bounds for DVH values while dose expected volume histograms can be used as central estimates for DVH when uncertainty is taken into account. They are particularly useful when an optimization approach is necessary.

Comparison of IPSM 1990 photon dosimetry code of practice with IAEA TRS-398 and AAPM TG-51.

Several codes of practice for photon dosimetry are currently used around the world, supported by different organizations. A comparison of IPSM 1990 with both IAEA TRS-398 and AAPM TG-51 has been performed. All three protocols are based on the calibration of ionization chambers in terms of standards of absorbed dose to water, as it is the case with other modern codes of practice. This comparison has been carried out for photon beams of nominal energies: 4 MV, 6 MV, 8 MV, 10 MV and 18 MV. An NE 2571 graphite ionization chamber was used in this study, cross-calibrated against an NE 2611A Secondary Standard, calibrated in the National Physical Laboratory (NPL). Absolute dose in reference conditions was obtained using each of these three protocols including: beam quality indices, beam quality conversion factors both theoretical and NPL experimental ones, correction factors for influence quantities and absolute dose measurements. Each protocol recommendations have been strictly followed. Uncertainties have been obtained according to the ISO Guide to the Expression of Uncertainty in Measurement. Absorbed dose obtained according to all three protocols agree within experimental uncertainty. The largest difference between absolute dose results for two protocols is obtained for the highest energy: 0.7% between IPSM 1990 and IAEA TRS-398 using theoretical beam quality conversion factors.

A novel method for the evaluation of uncertainty in dose-volume histogram computation.

PURPOSE: Dose-volume histograms (DVHs) are a useful tool in state-of-the-art radiotherapy treatment planning, and it is essential to recognize their limitations. Even after a specific dose-calculation model is optimized, dose distributions computed by using treatment-planning systems are affected by several sources of uncertainty, such as algorithm limitations, measurement uncertainty in the data used to model the beam, and residual differences between measured and computed dose. This report presents a novel method to take them into account. METHODS AND MATERIALS: To take into account the effect of associated uncertainties, a probabilistic approach using a new kind of histogram, a dose-expected volume histogram, is introduced. The expected value of the volume in the region of interest receiving an absorbed dose equal to or greater than a certain value is found by using the probability distribution of the dose at each point. A rectangular probability distribution is assumed for this point dose, and a formulation that accounts for uncertainties associated with point dose is presented for practical computations. RESULTS: This method is applied to a set of DVHs for different regions of interest, including 6 brain patients, 8 lung patients, 8 pelvis patients, and 6 prostate patients planned for intensity-modulated radiation therapy. CONCLUSIONS: Results show a greater effect on planning target volume coverage than in organs at risk. In cases of steep DVH gradients, such as planning target volumes, this new method shows the largest differences with the corresponding DVH; thus, the effect of the uncertainty is larger.

[Outliers and robust logistic regression in Health Sciences]. / Datos anómalos y regresión logística robusta en ciencias de la salud.

Logistic regression methods have many applications in Health Sciences. There is a vast literature about procedures to be followed and the way to find the estimators for the parameters from the observed values, and these methods are implemented to all the usual statistical packages. These estimators are of the 'maximum likelihood' kind, i.e., they are the ones that make the observed values the most probable among all the models that could have been used. The good properties of the maximum likelihood estimators are widely demonstrated. However, there are some practical circumstances that may cause the presence of 'outliers', i.e., observed values not corresponding to the logistic model we are assuming as a hypothesis. Occasionally, these anomalous observations can have a strong effect on the fit, and lead the study to the wrong conclusion. The causes of these outliers depend on the particular study, but it is possible to point out classification errors, observations (subjects) with special features which have not been taken into account, uncertainty in the measurement of some parameters, etc. The problem with maximum likelihood estimators is that they are not 'robust', i.e., their sensitivity to outliers could be arbitrarily large, and a minority of outliers could lead to a wrong logistic model. In this work, we will show two cases illustrating possible consequences, and we will discuss the application of robust methods.

[Laboratory diagnosis of dengue virus infections in Aragua State, Venezuela: October 1997-December 1998]. / Diagnóstico de laboratorio de infecciones por el virus dengue en el estado Aragua; Venezuela: Octubre 1997-Diciembre 1998.

The efficacy of a proactive dengue surveillance system to predict epidemics depends on the laboratory diagnostic capacity for an early detection of virus circulation. This study shows the results of the dengue virologic and serologic surveillance accomplished in Aragua State (Venezuela) from October 1997 to December 1998. Five hundred and forty seven sera from suspected dengue patients were tested using the techniques of Virus Isolation and Immunofluorescence Serotyping (VIIS), Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR), Anti-dengue IgM Capture Enzyme Immunoassay (MAC-ELISA) and Haemagglutination Inhibition test (HI). Of the tested sera, 97.4% resulted positive to at least one technique; of these, 60.4% were classified as confirmed cases (virologically positives) and 39.6% as probable cases (virologically negatives/serologically positives). Though the majority of positive cases occurred during the 1997 and 1998 epidemic periods, the gradual increase of the seropositive rates between both periods suggested the incoming 1998 outbreak. Den-1 (51.2%), Den-2 (37.9%) and Den-4 (10.6%) infected patients were detected as well as one dual infection of Den-2 and Den-4 (0.3%). Dengue hyperendemicity (co-circulation of Den-1, Den-2 and Den-4) in Aragua State was confirmed together with the detection of few cases (6.5%) of Dengue Hemorrhagic Fever/Dengue Shock Syndrome cases (HF/DSS); 38.1% of these cases occurred in patients with secondary infections. The high percentage (85.7%) of DHF/DSS cases infected by Den-2 virus supports the reported virulence of this serotype.

Diagnóstico de laboratorio de infecciones por el virus dengue en el estado Aragua Venezuela: octubre 1997-diciembre 1998 / Laboratory diagnosis of dengue virus infections in Aragua state Venezuela: october 1997-december 1998

La eficacia de un sistema de vigilancia epidemiológica proactivo para predecir epidemias de dengue de la capacidad del laboratorio para detectar tempranamente la circulación viral. Este estudio muestra los resultados de la vigilancia virológica del dengue, realizada en el estado Aragua (Venezuela) desde octubre 1997 hasta diciembre 1998. Se evluaron 547 sueros de pacientes sospechosos de dengue mediante las técnicas de aislamiento viral y serotipicación por inmunofluorescencia (AVSI), reacción en cadena de la polimerasa con transcriptasa inversa (RT-PCR), inmunoensayo enzimático de captura de IgM anti-dengue (MAC-ELISA) e inhibición de la hemaglutinación (IHA). De los sueros examinados, 97,4 por ciento resultaron positivos a por lo menos una técnica; de estos, 60,4 por ciento fueron clasificados como casos confirmados (virológicamente positivos) y 39,6 por ciento como casos probables (virológicamente negativos, serológicamente positivos). Aunque la gran mayoría de los casos positivos ocurrieron en los períodos epidémicos de 1997 y 1998, el incremento paulatino de las tasas de serotipos entre ambos períodos sugería la llegada de la epidemia de 1998. Se detectaron pacientes infectados con virus Den-1 (51,2 por ciento), Den-2 (37,9 por ciento), Den-4 (10,6 por ciento), y una infección mixta por Den-2 y Den-4 (0,3 por ciento). Se confirma la hiperdemicidad del dengue (co-circulación de Den-1, Den-2 y Den-4) en el estado Aragua, conjuntamente con la detección de pocos pasos (6,5 por ciento) de fiebre hemorrágica de dengue/síndrome de choque por dengue (FHD/SCD); 38,1 por ciento de estos casos ocurrieron en pacientes con infecciones secundarias. El alto porcentaje (85,7 por ciento) de casos de FHD/SCD infectados con el virus Den-2 apoya la reportada virulencia de este serotipo