Showing papers by "Alicia Rodríguez-Gascón published in 2018"

Augmented Renal Clearance in Critically Ill Patients: A Systematic Review

Abstract: Traditionally, renal function in critically ill patients has been assessed to identify renal dysfunction, and dose adjustment is generally accepted in such a context Nevertheless, augmented renal clearance (ARC) is a less well-studied phenomenon that could lead to faster elimination of drugs, resulting in subtherapeutic concentrations and poorer clinical outcomes when standard dosage guidelines are followed The aim of this systematic review was to gather and summarise all the available evidence on ARC in critically ill patients, including its definition, underlying mechanisms, epidemiology, diagnosis and impact on both drug pharmacokinetics and clinical outcomes A systematic review was conducted to include all the original studies that provided information on ARC in critically ill patients, and is reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines Augmented renal clearance, defined as a creatinine clearance (CrCl) > 130 mL/min/173 m2, preferably measured in urine, is present in 20–65% of critically ill patients Younger age, polytrauma and lower severity illness have been identified as risk factors An influence of ARC on antimicrobial pharmacokinetics has been observed, with ARC consistently being associated with subtherapeutic antibiotic plasma concentrations ARC is a prevalent condition in critically ill patients, especially in young people, with urinary CrCl being the best diagnostic method because mathematical estimates tend to underestimate CrCl ARC increases renal drug elimination and has a clear influence on certain antimicrobial plasma levels, but is yet to define its impact on clinical outcomes and on pharmacokinetics of other types of drugs Research on the need to stage ARC and establish specific dosing guidelines is warranted

Nonviral Delivery Systems for Gene Therapy for Retina and Posterior Segment Disease

Abstract: Gene therapy is a hopeful strategy for the treatment of retinal disorders with no effective treatment. Gene replacement therapy is the most widely used strategy to modulate the gene expression in clinical research of inherited or acquired ocular diseases. Viral vectors are at the forefront of translational gene therapy mainly due to their high efficacy; nevertheless, concerns regarding safety have fostered the progress of nonviral therapy. Nonviral systems are non-immunogenic and avoid the risk of insertional mutagenesis. Moreover, they can be easily produced at large scale and have the potential to deliver larger genetic payloads. However, vector engineering to attain tissue-selective targeting and/or regulate the extent of gene expression is a challenging issue of nonviral gene therapy. Subretinal or intravitreal injections are the best option for the success of gene delivery to the posterior segment of the eye, regardless of the type of vector used. Preclinical studies with nonviral vectors have shown encouraging results for the treatment of macular degeneration and some inherited retinal disorders such as X-linked retinoschisis, Stargardt disease, retinitis pigmentosa, and Leber congenital amaurosis. These recent advances point to nonviral gene therapy as a feasible therapeutic tool for retinal disorders.

Psychopharmacological Issues in Geriatrics

Abstract: Description: Demographic changes due to improved life expectancy and access to medical care has increased the number of people aged 65 years and beyond. This raises an important new challenge for healthcare professionals. Changes in organ functions, homeostatic mechanisms and receptor responsiveness impair drug distribution, metabolism and excretion, and reduce the effectiveness of medicines among geriatric patients. As a consequence, management of medical regimens is much more challenging in the elderly than in younger adult patients. Elderly patients are also more susceptible than other age groups to certain drugdrug interactions, drug-disease interactions and adverse drug reactions owing to the number of drugs administered.