E. Climent - Academia.edu (original) (raw)
Papers by E. Climent
Enfermedades infecciosas y microbiologia clinica (English ed.)
Farmacia Hospitalaria, 1999
European Journal of Hospital Pharmacy: Science and Practice, 2014
Background Switching from intravenous (IV) to oral (PO) treatment as soon as patients are clinica... more Background Switching from intravenous (IV) to oral (PO) treatment as soon as patients are clinically stable can reduce the costs associated with IV administration. In this study, we selected levetiracetam, a drug with high bioavailability oral (100%) and a significant cost difference between IV and PO forms. Purpose To estimate avoidable IV levetiracetam use and analyse the potential effect on the hospital drugs budget associated with changing levetiracetam from intravenous to oral treatment. Materials and methods Retrospective observational study performed in patients admitted to the neurosurgical service treated with IV levetiracetam from March 2013 to August 2013 (6 months). We divided levetiracetam-days (LD), into IV levetiracetam days (all doses of levetiracetam were administered IV), and PO levetiracetam days (at least 1 dose administered PO). And we considered IV levetiracetam avoidable when a patient received at least one other oral drug. Data source for costs were the average wholesale prices in 2013. Results A total of 38 patients (24 men, 63%) were included in the study with a mean age of 54.3 (95% CI, 49.1–59.4) years. During study 303 LD were counted, 107 (35%) IV levetiracetam days and 196 (65%) PO levetiracetam days and a median of 2 days IV treatment (interquartile range 1–3). In this period 84 (78.5%) IV levetiracetam days were potentially avoidable, and the cost savings for conversion from IV to PO levetiracetam were calculated to be 2,066 € and the total annual cost savings in the neurosurgery unit 4,132 €. Conclusions Early switching from IV to oral levetiracetam is possible and leads to a substantial reduction in the drugs bill. Explicit physiological criteria should be recorded to serve as a benchmark for successfully switching treatment. No conflict of interest.
International Journal of Pharmaceutics, 1990
In situ gastric absorption rate constants determined in rats for a series of phenylalkylcarboxyli... more In situ gastric absorption rate constants determined in rats for a series of phenylalkylcarboxylic acids in free solution were correlated with in vitro lipophilicity indexes. The correlations were bilinear in nature, in contrast with what occurs in other digestive absorption sites, where such correlations are always of the hyperbolic type. Bilinear correlations are found when heterogeneous barrier systems prevail at the absorption site; this conception seems to be in close agreement with the novel approaches describing the structure of the gastric mucosal surface, according to which a lipid lining of natural amphiphiles provides the mucosal surface with a physiological protection against its highly acid environment. This structure is not found in the intestinal mucosae, which act as homogeneous barrier systems. In the presence of surfactants in gastric perfusion fluids, the correlations became similar to those found in nonspecialized absorption sites such as colon. This would mean that the hydrophobic lining is disrupted by surfactants, thus leaving unprotected the absorbing membrane, which is then exposed to the aggressive surrounding medium. Physiological and pathological implications derived from these observations are discussed.
The American journal of gastroenterology, 1997
Quantification of liver function in patients with cirrhosis is difficult. Caffeine clearance (CCI... more Quantification of liver function in patients with cirrhosis is difficult. Caffeine clearance (CCI) has been suggested as a more exact method than those commonly used. The aim of this work was to assess the usefulness of CCl in survival prediction for these patients. Thirty-four patients with cirrhosis of the liver of various causes were included; 19 were class A or B in Child-Pugh's classification and 15 were class C. CCl was determined from saliva samples. The mean length of follow-up was 33.8 months. A bivariant survival analysis was carried out following the Kaplan-Meier method, together with a multivariant analysis using the Cox proportional hazards model. Twelve patients died during the follow-up period. CCl values < 0.24 ml/kg/min, age > 60 yr, and nonalcoholic cause of cirrhosis were factors predicting lower survival. CCl was the only independent predictive factor in the multivariant analysis. CCl enables us to predict survival in cirrhotic patients and, considering...
Enfermedades Infecciosas y Microbiología Clínica
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
International Journal of Pharmaceutics, 1994
ABSTRACT The effects of sodium glycocholate (SGC) on the intestinal absorption of drug-related xe... more ABSTRACT The effects of sodium glycocholate (SGC) on the intestinal absorption of drug-related xeriobiotics are investigated, on the basis of previously established absorption/partition relationships. Six phenylalkylcarboxylic acids, closely related to nonsteroid anti-inflammatory drugs in structure and constituting a true homologous series, were used as test compounds through an in situ rat gut technique, using the whole colon as nonspecialized absorption membrane model. Whereas the synthetic surfactants (i.e., polysorbates and laurylsulphates) at the critical micelle concentration have been shown to disrupt the aqueous boundary layer adjacent to the membrane, SGC does not; in contrast, it reinforces its limiting effect on solute diffusion, thus leading to a poorer absorption of the compounds as their lipophilicity increases. On the other hand, at supramicellar concentrations, the micelle solubilizing effect of SGC for the compounds is incomparably lower than that found for synthetics, even in the presence of mixed micelles with lecithin. These results, in conjunction with previous observations, seem to indicate that as far as xenobiotic absorption is concerned, synthetics and natural bile acid surfactants behave as entirely different biopharmaceutical species.
Journal of Computational Physics, 2015
Journal of Computational Physics, 2015
This contribution provides a general framework to use Lagrange multipliers for the simulation of ... more This contribution provides a general framework to use Lagrange multipliers for the simulation of low Reynolds number fiber dynamics based on Bead Models (BM). This formalism provides an efficient method to account for kinematic constraints. We illustrate, with several examples, to which extent the proposed formulation offers a flexible and versatile framework for the quantitative modeling of flexible fibers deformation and rotation in shear flow, the dynamics of actuated filaments and the propulsion of active swimmers. Furthermore, a new contact model called Gears Model is proposed and successfully tested. It avoids the use of numerical artifices such as repulsive forces between adjacent beads, a source of numerical difficulties in the temporal integration of previous Bead Models.
Notes on Numerical Fluid Mechanics and Multidisciplinary Design, 2014
Usualy, numerical simulations of two-phase particle dispersed flow both with Eulerian or Lagrangi... more Usualy, numerical simulations of two-phase particle dispersed flow both with Eulerian or Lagrangian approaches assume particle size to be smaller than the smallest scales of the carrier fluid, which is not the case for most two-phase dispersed flows. The present work aims at giving a detailed analysis of particle behaviour by performing fully resolved of finite size particle simulations in the case of forced homogeneous isotropic turbulence
In this work we investigate numerically the dynamics of sheared suspensions in the limit of vanis... more In this work we investigate numerically the dynamics of sheared suspensions in the limit of vanishingly small fluid and particle inertia. The numerical model we used is able to handle the multi-body hydrodynamic interactions between thousands of particles embedded in a linear shear flow. The presence of the particles is modelled by momentum source terms spread out on a spherical envelop forcing the Stokes equations of the creeping flow. Therefore all the velocity perturbations induced by the moving particles are simultaneously accounted for.
Producing nanoparticles in dense suspensions can be achieved in a stirred media mill. However the... more Producing nanoparticles in dense suspensions can be achieved in a stirred media mill. However the mechanisms of fragmentation in the mill are still not fully understood and the process remains laborious because of the large amount of supplied energy. We focus on the numerical analysis of the local hydrodynamics in the mill. Based on the flow simulations we determine the parameters which control the efficiency of the collisions between grinding beads (impact velocities and orientation of the collisions). The suspension flow (grinding beads, particles, carrying fluid) is modelled with effective physical properties. We solve directly the continuity and Navier-Stokes equations for the equivalent fluid assuming that the flow is two-dimensional and steady. Depending on the Reynolds number and the non-Newtonian behaviour of the fluid, we found that the flow is composed of several toroidal vortices. The most energetic collisions are driven by the strong shear experienced by the suspension within the gap between the disc tip and the wall chamber.
ChemInform, 2010
Phase Transition Induced by Pressure in TbCrO 4 Oxide: Relationship Structure--Properties. -The z... more Phase Transition Induced by Pressure in TbCrO 4 Oxide: Relationship Structure--Properties. -The zircon-type TbCrO4 polymorph (tetragonal, space group I41/amd) undergoes a phase transition at 40 kbar and 833 K to the scheelite-type polymorph (tetragonal, space group I41/a). The new scheelite-type polymorph shows antiferromagnetic behavior, while the zircon form is ferromagnetic. -(CLIMENT, E.; GALLARDO, J. M.; ROMERO DE PAZ, J.; TAIRA, N.; SAEZ PUCHE*, R.; J.
The dynamics of homogeneous, isotropic turbulence seeded with finite sized particles or bubbles i... more The dynamics of homogeneous, isotropic turbulence seeded with finite sized particles or bubbles is investigated in a series of numerical simulations, using the force-coupling method for the particle phase and low wavenumber forcing of the flow to sustain the turbulence. Results are given on the modulation of the turbulence due to massless bubbles, neutrally buoyant particles and inertial particles of specific density 1.4 at volumetric concentrations of 6%. Buoyancy forces due to gravity are excluded to emphasize finite size and inertial effects for the bubbles or particles and their interactions with the turbulence. Besides observing the classical entrapment of bubbles and the expulsion of inertial particles by vortex structures, we analyze the Lagrangian statistics for the velocity and acceleration of the dispersed phase. The turbulent fluctuations are damped at mid-range wavenumbers by the bubbles or particles while the smallscale kinetic energy is significantly enhanced. Unexpectedly, the modulation of turbulence depends only slightly on the dispersion characteristics (bubble entrapment in vortices or inertial sweeping of the solid particles) but is closely related to the stresslet component (finite size effect) of the flow disturbances. The pivoting wavenumber characterizing the transition from damped to enhanced energy content is shown to vary with the size of the bubbles or particles. The spectrum for the energy transfer by the particle phase is examined and the possibility of representing this, at large scales, through an additional effective viscosity is discussed.
International Journal of Pharmaceutics, 1994
... Arn. J. Med., 49 (1970) 590-608. Del Estal, JL, Alvarez, AI, Villa Verde, C., Coronel, P., Fa... more ... Arn. J. Med., 49 (1970) 590-608. Del Estal, JL, Alvarez, AI, Villa Verde, C., Coronel, P., Fabra, S. and Prieto, JG, Effect of surfactants on alben-MJ Sexura-Bono et al. /International Journal f Pharmacecttics 107 (1994) 159-166 dazole absorption. J. Pharm. Biomed. ...
Soft Matter, 2014
Based on direct numerical simulations of the coupled motion of particles and fluid, this study an... more Based on direct numerical simulations of the coupled motion of particles and fluid, this study analyzes the collective hydrodynamic and colloidal effects of flowing microparticles during the formation of different 3D clogging patterns at a pore entrance. Simulations of flowing suspensions through a pore with various simulation conditions show that particle concentration and surface interactions play a major role in the occurrence of the bridging phenomenon (simultaneous adhesion of many particles). In the absence of DLVO repulsive forces, plugging is characterized by the temporal reduction of the bulk permeability when increasing the volume fraction of the flowing suspension up to 20%. Under these conditions, different structures of particle aggregates (from cluster to cake plug) are formed at the pore entrance yielding different evolution rates of hydrodynamic resistance to the flow. Taking into account DLVO repulsive forces in simulations for a particle concentration equal to 10%, we observe the transition from dendritic structures (for low repulsion) to dense aggregates (for high repulsion). At high DLVO repulsive forces, the scenario of pore clogging is controlled by the collective behavior of many interacting particles. It leads to the formation of a jamming phase (Wigner glass phase) with transient clusters of interacting particles at the pore entrance. The network of jammed particles collapses when the force chains among the particles are overcome by the flow stress. The build-up and the collapse of the jammed phase at the pore entrance induce temporal permeability fluctuations. According to the relative magnitude of particle-particle and particle-wall interactions, when the jammed phase is disorganized by the flow, the residual force in the network can accelerate particles and lead to particle adhesion at the wall inducing a pore blockage and a rapid reduction of the bulk permeability.
Enfermedades infecciosas y microbiologia clinica (English ed.)
Farmacia Hospitalaria, 1999
European Journal of Hospital Pharmacy: Science and Practice, 2014
Background Switching from intravenous (IV) to oral (PO) treatment as soon as patients are clinica... more Background Switching from intravenous (IV) to oral (PO) treatment as soon as patients are clinically stable can reduce the costs associated with IV administration. In this study, we selected levetiracetam, a drug with high bioavailability oral (100%) and a significant cost difference between IV and PO forms. Purpose To estimate avoidable IV levetiracetam use and analyse the potential effect on the hospital drugs budget associated with changing levetiracetam from intravenous to oral treatment. Materials and methods Retrospective observational study performed in patients admitted to the neurosurgical service treated with IV levetiracetam from March 2013 to August 2013 (6 months). We divided levetiracetam-days (LD), into IV levetiracetam days (all doses of levetiracetam were administered IV), and PO levetiracetam days (at least 1 dose administered PO). And we considered IV levetiracetam avoidable when a patient received at least one other oral drug. Data source for costs were the average wholesale prices in 2013. Results A total of 38 patients (24 men, 63%) were included in the study with a mean age of 54.3 (95% CI, 49.1–59.4) years. During study 303 LD were counted, 107 (35%) IV levetiracetam days and 196 (65%) PO levetiracetam days and a median of 2 days IV treatment (interquartile range 1–3). In this period 84 (78.5%) IV levetiracetam days were potentially avoidable, and the cost savings for conversion from IV to PO levetiracetam were calculated to be 2,066 € and the total annual cost savings in the neurosurgery unit 4,132 €. Conclusions Early switching from IV to oral levetiracetam is possible and leads to a substantial reduction in the drugs bill. Explicit physiological criteria should be recorded to serve as a benchmark for successfully switching treatment. No conflict of interest.
International Journal of Pharmaceutics, 1990
In situ gastric absorption rate constants determined in rats for a series of phenylalkylcarboxyli... more In situ gastric absorption rate constants determined in rats for a series of phenylalkylcarboxylic acids in free solution were correlated with in vitro lipophilicity indexes. The correlations were bilinear in nature, in contrast with what occurs in other digestive absorption sites, where such correlations are always of the hyperbolic type. Bilinear correlations are found when heterogeneous barrier systems prevail at the absorption site; this conception seems to be in close agreement with the novel approaches describing the structure of the gastric mucosal surface, according to which a lipid lining of natural amphiphiles provides the mucosal surface with a physiological protection against its highly acid environment. This structure is not found in the intestinal mucosae, which act as homogeneous barrier systems. In the presence of surfactants in gastric perfusion fluids, the correlations became similar to those found in nonspecialized absorption sites such as colon. This would mean that the hydrophobic lining is disrupted by surfactants, thus leaving unprotected the absorbing membrane, which is then exposed to the aggressive surrounding medium. Physiological and pathological implications derived from these observations are discussed.
The American journal of gastroenterology, 1997
Quantification of liver function in patients with cirrhosis is difficult. Caffeine clearance (CCI... more Quantification of liver function in patients with cirrhosis is difficult. Caffeine clearance (CCI) has been suggested as a more exact method than those commonly used. The aim of this work was to assess the usefulness of CCl in survival prediction for these patients. Thirty-four patients with cirrhosis of the liver of various causes were included; 19 were class A or B in Child-Pugh's classification and 15 were class C. CCl was determined from saliva samples. The mean length of follow-up was 33.8 months. A bivariant survival analysis was carried out following the Kaplan-Meier method, together with a multivariant analysis using the Cox proportional hazards model. Twelve patients died during the follow-up period. CCl values < 0.24 ml/kg/min, age > 60 yr, and nonalcoholic cause of cirrhosis were factors predicting lower survival. CCl was the only independent predictive factor in the multivariant analysis. CCl enables us to predict survival in cirrhotic patients and, considering...
Enfermedades Infecciosas y Microbiología Clínica
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
International Journal of Pharmaceutics, 1994
ABSTRACT The effects of sodium glycocholate (SGC) on the intestinal absorption of drug-related xe... more ABSTRACT The effects of sodium glycocholate (SGC) on the intestinal absorption of drug-related xeriobiotics are investigated, on the basis of previously established absorption/partition relationships. Six phenylalkylcarboxylic acids, closely related to nonsteroid anti-inflammatory drugs in structure and constituting a true homologous series, were used as test compounds through an in situ rat gut technique, using the whole colon as nonspecialized absorption membrane model. Whereas the synthetic surfactants (i.e., polysorbates and laurylsulphates) at the critical micelle concentration have been shown to disrupt the aqueous boundary layer adjacent to the membrane, SGC does not; in contrast, it reinforces its limiting effect on solute diffusion, thus leading to a poorer absorption of the compounds as their lipophilicity increases. On the other hand, at supramicellar concentrations, the micelle solubilizing effect of SGC for the compounds is incomparably lower than that found for synthetics, even in the presence of mixed micelles with lecithin. These results, in conjunction with previous observations, seem to indicate that as far as xenobiotic absorption is concerned, synthetics and natural bile acid surfactants behave as entirely different biopharmaceutical species.
Journal of Computational Physics, 2015
Journal of Computational Physics, 2015
This contribution provides a general framework to use Lagrange multipliers for the simulation of ... more This contribution provides a general framework to use Lagrange multipliers for the simulation of low Reynolds number fiber dynamics based on Bead Models (BM). This formalism provides an efficient method to account for kinematic constraints. We illustrate, with several examples, to which extent the proposed formulation offers a flexible and versatile framework for the quantitative modeling of flexible fibers deformation and rotation in shear flow, the dynamics of actuated filaments and the propulsion of active swimmers. Furthermore, a new contact model called Gears Model is proposed and successfully tested. It avoids the use of numerical artifices such as repulsive forces between adjacent beads, a source of numerical difficulties in the temporal integration of previous Bead Models.
Notes on Numerical Fluid Mechanics and Multidisciplinary Design, 2014
Usualy, numerical simulations of two-phase particle dispersed flow both with Eulerian or Lagrangi... more Usualy, numerical simulations of two-phase particle dispersed flow both with Eulerian or Lagrangian approaches assume particle size to be smaller than the smallest scales of the carrier fluid, which is not the case for most two-phase dispersed flows. The present work aims at giving a detailed analysis of particle behaviour by performing fully resolved of finite size particle simulations in the case of forced homogeneous isotropic turbulence
In this work we investigate numerically the dynamics of sheared suspensions in the limit of vanis... more In this work we investigate numerically the dynamics of sheared suspensions in the limit of vanishingly small fluid and particle inertia. The numerical model we used is able to handle the multi-body hydrodynamic interactions between thousands of particles embedded in a linear shear flow. The presence of the particles is modelled by momentum source terms spread out on a spherical envelop forcing the Stokes equations of the creeping flow. Therefore all the velocity perturbations induced by the moving particles are simultaneously accounted for.
Producing nanoparticles in dense suspensions can be achieved in a stirred media mill. However the... more Producing nanoparticles in dense suspensions can be achieved in a stirred media mill. However the mechanisms of fragmentation in the mill are still not fully understood and the process remains laborious because of the large amount of supplied energy. We focus on the numerical analysis of the local hydrodynamics in the mill. Based on the flow simulations we determine the parameters which control the efficiency of the collisions between grinding beads (impact velocities and orientation of the collisions). The suspension flow (grinding beads, particles, carrying fluid) is modelled with effective physical properties. We solve directly the continuity and Navier-Stokes equations for the equivalent fluid assuming that the flow is two-dimensional and steady. Depending on the Reynolds number and the non-Newtonian behaviour of the fluid, we found that the flow is composed of several toroidal vortices. The most energetic collisions are driven by the strong shear experienced by the suspension within the gap between the disc tip and the wall chamber.
ChemInform, 2010
Phase Transition Induced by Pressure in TbCrO 4 Oxide: Relationship Structure--Properties. -The z... more Phase Transition Induced by Pressure in TbCrO 4 Oxide: Relationship Structure--Properties. -The zircon-type TbCrO4 polymorph (tetragonal, space group I41/amd) undergoes a phase transition at 40 kbar and 833 K to the scheelite-type polymorph (tetragonal, space group I41/a). The new scheelite-type polymorph shows antiferromagnetic behavior, while the zircon form is ferromagnetic. -(CLIMENT, E.; GALLARDO, J. M.; ROMERO DE PAZ, J.; TAIRA, N.; SAEZ PUCHE*, R.; J.
The dynamics of homogeneous, isotropic turbulence seeded with finite sized particles or bubbles i... more The dynamics of homogeneous, isotropic turbulence seeded with finite sized particles or bubbles is investigated in a series of numerical simulations, using the force-coupling method for the particle phase and low wavenumber forcing of the flow to sustain the turbulence. Results are given on the modulation of the turbulence due to massless bubbles, neutrally buoyant particles and inertial particles of specific density 1.4 at volumetric concentrations of 6%. Buoyancy forces due to gravity are excluded to emphasize finite size and inertial effects for the bubbles or particles and their interactions with the turbulence. Besides observing the classical entrapment of bubbles and the expulsion of inertial particles by vortex structures, we analyze the Lagrangian statistics for the velocity and acceleration of the dispersed phase. The turbulent fluctuations are damped at mid-range wavenumbers by the bubbles or particles while the smallscale kinetic energy is significantly enhanced. Unexpectedly, the modulation of turbulence depends only slightly on the dispersion characteristics (bubble entrapment in vortices or inertial sweeping of the solid particles) but is closely related to the stresslet component (finite size effect) of the flow disturbances. The pivoting wavenumber characterizing the transition from damped to enhanced energy content is shown to vary with the size of the bubbles or particles. The spectrum for the energy transfer by the particle phase is examined and the possibility of representing this, at large scales, through an additional effective viscosity is discussed.
International Journal of Pharmaceutics, 1994
... Arn. J. Med., 49 (1970) 590-608. Del Estal, JL, Alvarez, AI, Villa Verde, C., Coronel, P., Fa... more ... Arn. J. Med., 49 (1970) 590-608. Del Estal, JL, Alvarez, AI, Villa Verde, C., Coronel, P., Fabra, S. and Prieto, JG, Effect of surfactants on alben-MJ Sexura-Bono et al. /International Journal f Pharmacecttics 107 (1994) 159-166 dazole absorption. J. Pharm. Biomed. ...
Soft Matter, 2014
Based on direct numerical simulations of the coupled motion of particles and fluid, this study an... more Based on direct numerical simulations of the coupled motion of particles and fluid, this study analyzes the collective hydrodynamic and colloidal effects of flowing microparticles during the formation of different 3D clogging patterns at a pore entrance. Simulations of flowing suspensions through a pore with various simulation conditions show that particle concentration and surface interactions play a major role in the occurrence of the bridging phenomenon (simultaneous adhesion of many particles). In the absence of DLVO repulsive forces, plugging is characterized by the temporal reduction of the bulk permeability when increasing the volume fraction of the flowing suspension up to 20%. Under these conditions, different structures of particle aggregates (from cluster to cake plug) are formed at the pore entrance yielding different evolution rates of hydrodynamic resistance to the flow. Taking into account DLVO repulsive forces in simulations for a particle concentration equal to 10%, we observe the transition from dendritic structures (for low repulsion) to dense aggregates (for high repulsion). At high DLVO repulsive forces, the scenario of pore clogging is controlled by the collective behavior of many interacting particles. It leads to the formation of a jamming phase (Wigner glass phase) with transient clusters of interacting particles at the pore entrance. The network of jammed particles collapses when the force chains among the particles are overcome by the flow stress. The build-up and the collapse of the jammed phase at the pore entrance induce temporal permeability fluctuations. According to the relative magnitude of particle-particle and particle-wall interactions, when the jammed phase is disorganized by the flow, the residual force in the network can accelerate particles and lead to particle adhesion at the wall inducing a pore blockage and a rapid reduction of the bulk permeability.