Association between 8 P-glycoprotein (MDR1/ABCB1) gene polymorphisms and antipsychotic drug-induced hyperprolactinaemia

INTRODUCTION: Hyperprolactinaemia, a common adverse effect of antipsychotic drugs, is primarily linked to blockade of dopamine D2 receptors in the pituitary gland. Certain antipsychotic drugs, such as, for example risperidone and paliperidone, are more likely to induce hyperprolactinaemia compared to others. This effect is probably caused by a relatively high blood/brain concentration ratio, a consequence of being a substrate of P-glycoprotein. Genetic variants of P-glycoprotein with changed functional activity might influence the potential of risperidone and paliperidone to cause hyperprolactinaemia as the altered blood/brain concentration ratio would lead to a reduced therapeutic drug level within essential brain areas making dose adaptations necessary. This increases exposure of dopamine D2 receptors within the pituitary gland. AIMS: To investigate possible associations between MDR1/ABCB1 gene polymorphisms and antipsychotic drug-induced hyperprolactinaemia in Russian patients with schizophrenia and to determine possible differences between risperidone/paliperidone and other antipsychotics. METHODS: In total, 446 patients with schizophrenia were included from 3 psychiatric hospitals in Siberia. Blood samples were obtained in a cross-sectional study design for DNA extraction and prolactin measurement. Associations between hyperprolactinaemia and 8 MDR1/ABCB1 gene-polymorphisms were assessed using logistic regression analysis accounting for covariates. The analysis was repeated in a patient subgroup using risperidone or paliperidone. RESULTS: We did not observe an association between any of the 8 single nucleotide polymorphisms and the prevalence of antipsychotic-induced hyperprolactinaemia in the total patient population. However, in the risperidone/paliperidone subgroup, the single nucleotide polymorphism rs2032582 (G2677T) was found to be negatively associated with risperidone/paliperidone-induced hyperprolactinaemia. CONCLUSION: This study revealed a significant association between the ABCB1 gene polymorphism rs2032582 (G2677T) and risperidone/paliperidone-induced hyperprolactinaemia

People’s understanding of verbal risk descriptors in patient information leaflets : a cross-sectional national survey of 18- to 65-year-olds in England

Introduction Evidence suggests the current verbal risk descriptors used to communicate side effect risk in patient information leaflets (PILs) are overestimated. Objectives The aim was to establish how people understand the verbal risk descriptors recommended for use in PILs by the European Commission (EC), and alternative verbal risk descriptors, in the context of mild and severe side effects. Methods A cross-sectional online survey was carried out by a market research company recruiting participants aged between 18 and 65 years living in England. Data were collected between 18 March and 1 April 2016. Participants were given a hypothetical scenario regarding the risk of mild or severe medication side effects and asked to estimate how many out of 10,000 people would be affected for each of the verbal risk descriptors being tested. Results A total of 1003 participants were included in the final sample. The risks conveyed by the EC recommended verbal risk descriptors were greatly overestimated by participants. Two distinct distributions were apparent for participant estimates of side effect risks: those for ‘high risk’ verbal descriptors (e.g. ‘common’, ‘likely’, ‘high chance’) and those for ‘low risk’ verbal descriptors (e.g. ‘uncommon’, ‘unlikely’, ‘low chance’). Within these two groups, the distributions were near to identical regardless of what adverb (e.g. very, high, fair) or adjective (e.g. common, likely, chance) was used. The EC recommended verbal risk descriptors were more likely to be understood in accordance with their intended meanings when describing severe side effects. Very few demographic or psychological factors were consistently associated with how well participants understood the EC recommended verbal risk descriptors. Discussion The current verbal risk descriptors used in PILs are ineffective at best and misleading at worst. Discontinuing the use of verbal risk descriptors would limit the likelihood of people overestimating the risk of side effects

Masticator space abscess derived from odontogenic infection: imaging manifestation and pathways of extension depicted by CT and MR in 30 patients

Propagation of odontogenic masticator space abscesses is insufficiently understood. The purpose was to analyse pathways of spread in 30 patients with odontogenic masticator space abscess. The imaging findings in 30 patients (CT in 30, MR in 16 patients) were retrospectively analysed. CT and MR imaging depicted a masticator space abscess within: medial pterygoid muscle in 13 patients (43.3%), lateral masseter and/or pterygoid muscle in 14 (46.7%) and superficial temporal muscle in 3 patients (10%). In the lateral masticator space intra-spatial abscess extension occurred in 7 of 14 patients (50%). The sub-masseteric space provided a pathway in seven (70%). Extra-spatial extension involved the submandibular space only in 3 of 14 patients (21.4%). Medial masticator space abscesses exhibited extra-spatial spread only. Extension affected the parapharyngeal space and/or soft palate in 7 of 13 lesions (53.8%). MR imaging in comparison to CT increased the number of abscess locations from 18 to 23 (27.8%) and regions affected by a cellular infiltrate from 12 to 16 (33.3%). The sub-masseteric space served as a previously underestimated pathway for intra-spatial propagation of lateral masticator abscesses. Medial masticator space abscesses tend to display early extra-spatial parapharyngeal space and/or soft palate extension

Flow modelling of quasi-Newtonian fluids in two-scale fibrous fabrics: Advanced simulations

Permeability is the fundamental macroscopic material property needed to quantify the flow in a fibrous medium viewed as a porous medium. Composite processing models require the permeability as input data to predict flow patterns and pressure fields. In a previous work, the expressions of macroscopic permeability were derived in a double-scale porosity medium for both Newtonian and generalized Newtonian (shear-thinning) resins. In the linear case, only a microscopic calculation on a representative volume is required, implying as many microscopic calculations as there are representative microscopic volumes in the whole fibrous structure. In the non-linear case, and even when the porous microstructure can be described by a unique representative volume, a large number of microscopic calculations must be carried out as the microscale resin viscosity depends on the macroscopic velocity, which in turn depends on the permeability that results from a microscopic calculation. An original and efficient offline-online procedure was proposed for the solution of non-linear flow problems related to generalized Newtonian fluids in porous media. In this paper, this procedure is generalized to quasi-Newtonian fluids in order to evaluate the effect of extensional viscosity on the resulting upscaled permeability. This work constitutes a natural step forward in the definition of equivalent saturated permeabilities for linear and non-linear fluids