Cost-Effectiveness of Therapeutic Drug Monitoring of Anti-TNF Therapy in Inflammatory Bowel Disease: A Systematic Review

Infliximab and adalimumab are monoclonal antibodies against tumor necrosis factor (anti-TNF) used to manage inflammatory bowel disease (IBD). Therapeutic Drug Monitoring (TDM) has been proven to prevent immunogenicity, to achieve better long-term clinical results and to save costs in IBD treatment. The aim of this study was to conduct a systematic review on cost-effectiveness analyses of studies that apply TDM of anti-TNF in IBD and to provide a critical analysis of the best scientific knowledge available in the literature. The quality of the included studies was assessed using Consolidated Health Economic Evaluation Reporting Standards (CHEERS). Cost-effectiveness of the TDM strategies was presented as total costs, cost savings, quality-adjusted life-years (QALY) and incremental cost-effectiveness ratio (ICER). Thirteen studies that examined the health economics of TDM of anti-TNF in IBD from 2013 to 2021 were included. Eight of them (61.5%) achieved a score between 17 and 23 on the CHEERS checklist. The comparison between the TDM strategy and an empirical strategy was cost saving. The ICER between reactive TDM and an empirical strategy was dominated (favorable) by reactive TDM, whereas the ICER value for proactive TDM compared to an empirical strategy ranged from EUR 56,845 to 3,901,554. This systematic review demonstrated that a TDM strategy is cost-effective or cost-saving in IBD.S.M.-M. received a predoctoral fellowship from Miguel Hernandez University (“Ayudas a la contratación de personal investigador en formación 2021”).S

Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genes

Background: Telomeres are nucleoprotein structures present at the terminal region of the chromosomes. Mutations in genes coding for proteins involved in telomere maintenance are causative of a number of disorders known as telomeropathies. The genetic origin of these diseases is heterogeneous and has not been determined for a significant proportion of patients. Methods: This article describes the genetic characterization of a cohort of patients. Telomere length was determined by Southern blot and quantitative PCR. Nucleotide variants were analyzed either by high-resolution melting analysis and Sanger sequencing of selected exons or by massive sequencing of a panel of genes. Results: Forty-seven patients with telomere length below the 10% of normal population, affected with three telomeropathies: dyskeratosis congenita (4), aplastic anemia (22) or pulmonary fibrosis (21) were analyzed. Eighteen of these patients presented known pathogenic or novel possibly pathogenic variants in the telomere-related genes TERT, TERC, RTEL1, CTC1 and ACD. In addition, the analyses of a panel of 188 genes related to haematological disorders indicated that a relevant proportion of the patients (up to 35%) presented rare variants in genes related to DNA repair or in genes coding for proteins involved in the resolution of complex DNA structures, that participate in telomere replication. Mutations in some of these genes are causative of several syndromes previously associated to telomere shortening

Cyclodepsipeptides from Marine Sponges: Natural Agents for Drug Research

A number of natural products from marine sponges, such as cyclodepsipeptides, have been identified. The structural characteristics of this family of cyclic peptides include various unusual amino acid residues and unique N-terminal polyketide-derived moieties. Papuamides are representatives of a class of marine sponge derived cyclic depsipeptides, including callipeltin A, celebesides A and B, homophymine A, mirabamides, microspinosamide, neamphamide A and theopapuamides. They are thought to have cytoprotective activity against HIV-1 in vitro by inhibiting viral entry. Jasplakinolide, a representative member of marine sponge-derived cyclodepsipeptides that include arenastatin A, geodiamolides, homophymines, spongidepsin and theopapuamides, is a potent inducer of actin polymerization in vitro. Although actin dynamics is essential for tumor metasasis, no actin targeting drugs have been used in clinical trials due to their severe cytotoxicity. Nonetheless, the actin cytoskeleton remains a potential target for anti-cancer drug development. These features imply the use of cyclodepsipeptides as molecular models in drug research

Antitumor Peptides from Marine Organisms

The biodiversity of the marine environment and the associated chemical diversity constitute a practically unlimited resource of new antitumor agents in the field of the development of marine bioactive substances. In this review, the progress on studies of antitumor peptides from marine sources is provided. The biological properties and mechanisms of action of different marine peptides are described; information about their molecular diversity is also presented. Novel peptides that induce apoptosis signal pathway, affect the tubulin-microtubule equilibrium and inhibit angiogenesis are presented in association with their pharmacological properties. It is intended to provide useful information for further research in the fields of marine antitumor peptides

La gestión académica en pandemia : adecuaciones, innovaciones y desafíos de la Universidad Nacional de Cuyo

Este libro remite a un contexto especial e inédito que surge a partir de la pandemia de covid-19. Se trata de un contexto de alcance global signado por efectos intensos y perdurables sobre diferentes aspectos de la realidad social, económica y ambiental. En general, estos efectos provocaron, por un lado, situaciones problemáticas nuevas y, por otro lado, agravaron situaciones problemáticas preexistentes que adquirieron mayor visibilidad. En el caso argentino, las restricciones derivadas de la pandemia agudizaron la brecha socioeducativa existente y, al mismo tiempo, exigieron una gestión ágil, dinámica, resolutiva, propositiva y resiliente, especialmente a las instituciones educativas con el objeto de asegurar el derecho a la educación y su calidad. Lógicamente, la provincia de Mendoza y, por tanto, la Universidad Nacional de Cuyo (UNCUYO) no quedaron exentas de los efectos mencionados. Aunque aún no resulta posible identificar con rigor el impacto concreto que ha tenido la pandemia sobre el funcionamiento del sistema educativo provincial, se pueden entrever algunos indicadores que vale la pena atender. Por ejemplo, el egreso en la oferta de educación superior de la uncuyo registró, en 2020, una caída interanual cercana al -18 % 1. Esta oscilación se torna más relevante si se considera que este indicador se mostraba estable a lo largo de los últimos años.Fil: Castañeda, Linda. Universidad de Murcia.Fil: Viñoles Cosentino, Virginia. Universidad de Murcia.Fil: Falcón, Paulo.Fil: Martínez, Ana María.Fil: Meljin Lombard, Mariela Beatriz. Universidad Nacional de Cuyo. Facultad de Artes y Diseño.Fil: Van Den Bosch, Silvia. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias.Fil: Castro, María Eugenia. Universidad Nacional de Cuyo. Facultad de Ciencias Aplicadas a la Industria.Fil: Puebla, Patricia. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas.Fil: Sánchez, Esther Lucía. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas.Fil: González Gaviola, Miguel. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas.Fil: Tarabelli, María Florencia. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales.Fil: Rüttler, María Elena. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas.Fil: Nalda, Gonzalo. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas.Fil: Castiglia, Mariana. Universidad Nacional de Cuyo. Facultad de Ciencias Políticas y Sociales.Fil: Mussuto, Matías M.. Universidad Nacional de Cuyo. Facultad de Derecho.Fil: Griffouliere, María Gabriela. Universidad Nacional de Cuyo. Facultad de Educación.Fil: Verstraete, María Ana. Universidad Nacional de Cuyo. Facultad de Filosofía y Letras.Fil: Echagaray, Patricia. Universidad Nacional de Cuyo. Facultad de Odontología.Fil: Mirasso, Aníbal. Universidad Nacional de Cuyo. Facultad de Ingeniería.Fil: Molina, Fabiana. Universidad Nacional de Cuyo. Instituto Tecnológico Universitario.Fil: Corral, Patricia. Universidad Nacional de Cuyo. Instituto Universitario de Seguridad Pública.Fil: Chrabalowski, Marina. Universidad Nacional de Cuyo.Fil: Barrozo, María Ana. Universidad Nacional de Cuyo.Fil: Zabala, Cecilia. Universidad Nacional de Cuyo. Escuela de Comercio Martín Zapata.Fil: Sauer, Marcelo. Universidad Nacional de Cuyo.Fil: Romero Day, Marcela. Universidad Nacional de Cuyo. Liceo Agrícola y Enológico Domingo F. Sarmiento.Fil: Marlia, Nora. Universidad Nacional de Cuyo. Facultad de Filosofía y Letras. Departamento de Aplicación Docente.Fil: Zamorano, Cristina. Universidad Nacional de Cuyo. Colegio Universitario Central.Fil: Yapura, Susana. Universidad Nacional de Cuyo. Escuela del Magisterio.Fil: Navarro, María Fernanda. Universidad Nacional de Cuyo.Fil: Bosio, Iris Viviana. Universidad Nacional de Cuyo. EDIUNC.Fil: Degiorgi, Horacio. Universidad Nacional de Cuyo. Sistema Integrado de Documentación.Fil: Bocco, María Susana. Universidad Nacional de Cuyo.Fil: Guayco, Mariana. Universidad Nacional de Cuyo.Fil: Pizzi, Daniel. Universidad Nacional de Cuyo.Fil: Lettelier, Dolores. Universidad Nacional de Cuyo. Secretaría Académica

Assessement and modulation of acamprosate intestinal absorption: comparative studies using in situ, in vitro (CACO-2 cell monolayers) and in vivo models

The purpose of this study was to explore the intestinal absorption mechanism of acamprosate and to attempt to improve the bioavailability (BA) of the drug through modulation of its intestinal absorption using two enhancers (polysorbate 80 and sodium caprate) based on in situ, in vitro and in vivo models and comparing the results obtained. Intestinal transport of the drug, in the absence and in presence of polysorbate 80 (0.06, 0.28 and 9.6 mM) or sodium caprate (13 and 16 mM) was measured by using an in situ rat gut technique and Caco-2 cell monolayers. Additionally, the effect of sodium caprate on drug oral bioavailability, measured as urinary recovery, was quantified by performing in vivo experiments with the rat as animal model. Only sodium caprate was able to increase the absorption rate constant (ka) of acamprosate in the mid-intestine of the rats from 0.29 ± 0.07 h−1 in the absence of the promoter to 0.51 ± 0.19 h−1 in the presence of C10 16 mM, along with the apparent permeability (Papp) obtained in Caco-2 cells (around two-fold). However, the drug bioavailability in rats (around 20%) did not improve in the presence of any of the concentrations tested (13, 16 and 50 mM). It is concluded that acamprosate absorption likely occurs via paracellular pathway and can be enhanced by sodium caprate in situ and in vitro but not in vivo thus suggesting that although in situ and in vitro studies could be useful in early screening to select a potential promoter, in vivo studies in animal models are necessary to confirm the utility of the enhancer and to determine the influence of physiological variables

Development of a Population Pharmacokinetic Model of Busulfan in Children and Evaluation of Different Sampling Schedules for Precision Dosing

We develop a population pharmacokinetic model to describe Busulfan pharmacokinetics in paediatric patients and investigate by simulations the impact of various sampling schedules on the calculation of AUC. Seventy-six children had 2 h infusions every 6 h. A two-compartment linear model was found to adequately describe the data. A lag-time was introduced to account for the delay of the administration of the drug through the infusion pump. The mean values of clearance, central volume of distribution, intercompartmental clearance, and peripheral volume of distribution were 10.7 L/h, 39.5 L, 4.68 L/h and 17.5 L, respectively, normalized for a Body Weight (BW) of 70 kg. BW was found to explain a portion of variability with an allometric relationship and fixed exponents of 0.75 on clearance parameters and 1 on volumes. Interindividual variability for clearance and volume of distribution was found to be 28% and 41%, respectively, and interoccasion variability for clearance was found to be 11%. Three sampling schedules were assessed by simulations for bias and imprecision to calculate AUC by a non-compartmental and a model-based method. The latter was found to be superior in all cases, while the non-compartmental was unbiased only in sampling up to 12 h corresponding to a once-daily dosing regimen. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Pharmacokinetic studies of linezolid and teicoplanin in the critically ill

Objectives: To determine the pharmacokinetic characteristics of linezolid and teicoplanin in critically ill patients. Patients and methods: Serum was collected frequently during day 0 and then pre- and 1 h post-dose on days 1, 2, 3, 5, 7 and every third day thereafter during treatment. Serum linezolid concentrations were analysed using HPLC. Serum teicoplanin levels were analysed by fluorescence polarization immunoassay. Results: A two-compartment model was required to characterize linezolid pharmacokinetics (n = 28) and account for the accumulation seen after multiple dosing. The estimated clearance was 0.049 ± 0.016 L/h/kg (±S.E.M. of estimate). At steady state (dosing interval 12 h), linezolid serum concentrations exceeded the breakpoint of 4mg/L for 10.88h (95% Cl 10.09-11.66) after a 600 mg dose with an AUC/MIC of 92.4 (95% Cl 57.2-127.7). Teicoplanin was best described by a two-compartment model (n = 26). The clearance was 4.97 ± 1.58 L/h. Serum levels exceeded the breakpoint of 4 mg/L for the entire dosing interval in all subjects (400 mg dose every 12 h) with an AUC/MIC of 399.3 (95% Cl 329.6-469.0). However, only four of 14 exceeded trough serum concentrations of 10 mg/L. For both agents, trough levels were similar in those who survived and those who died. Conclusions: Linezolid dosage at 600 mg every 12 h was adequate in the critically ill without need for adjustment for renal function. For teicoplanin, further study is needed to confirm if a trough of 10 mg/L is associated with a higher rate of cure than 5 mg/L. If so, serum drug assays would be needed to ensure a therapeutic level. © The British Society for Antimicrobial Chemotherapy 2005; all rights reserved