Borja Santos

Unidimensional 12-Item Zarit Caregiver Burden Interview for the Assessment of Dementia Caregivers' Burden Obtained by Item Response Theory

OBJECTIVES To develop a one-dimensional version of the 22-item Zarit Caregiver Burden Interview (ZBI) by applying item response theory approaches. METHODS The answers to the 22-item ZBI of 241 caregivers participating in a clinical trial were analyzed 1) with a Mokken nonparametric item response theory analysis to ascertain the dimensional structure underlying the scale and obtain a one-dimensional reduced version, 2) with the Samejimas graded response model to assess the item characteristics of the reduced version, and 3) with confirmatory factor analysis to confirm the unidimensionality of the reduced ZBI version and assess the item loadings to the burden latent variable. RESULTS Mokken analysis resulted in a major one-dimensional scale comprising 12 items directly related with burden. All items showed scalability indices over 0.30. The scalability for the overall scale was 0.44 defining a medium scale according to Mokkens criteria. An unconstrained Samejimas graded response model showed appropriate fit, and most items of the reduced 12-item ZBI presented pertinent difficulty and discrimination parameters. The results of the 12-item ZBI confirmatory factor analysis fitted to a one-dimensional latent structure for burden (comparative fit index=0.975; root-mean-square error of approximation=0.067; weighted root mean square residual=0.677). All factor lodgings were above 0.40 with items 9 (strained by the relative) and 22 (overall feeling of burden) presenting the highest loadings. CONCLUSIONS The reduced 12-item ZBI fits a one-dimensional latent variable of burden. Further psychometric studies, focusing on its equivalence for different populations, sensitivity to change, and minimal important difference are warranted.

Mir-pharmacogenetics of Vincristine and peripheral neurotoxicity in childhood B-cell acute lymphoblastic leukemia

Vincristine (VCR), an important component of childhood acute lymphoblastic leukemia (ALL) therapy, can cause sensory and motor neurotoxicity. This neurotoxicity could lead to dose reduction or treatment discontinuation, which could in turn reduce survival. In this line, several studies associated peripheral neurotoxicity and polymorphisms in genes involved in pharmacokinetics (PK) and pharmacodynamics (PD) of VCR. Nowadays, it is well known that these genes are regulated by microRNAs (miRNAs) and SNPs in miRNAs could modify their levels or function. Therefore, the aim of this study was to determine whether SNPs in miRNAs could be associated with VCR-induced neurotoxicity. To achieve this aim, we analyzed all the SNPs in miRNAs (minor allele frequency (MAF) ≥ 0.01) which could regulate VCR-related genes in a large cohort of Spanish children with B-cell precursor ALL (B-ALL) homogeneously treated with LAL/SHOP protocols. We identified the A allele of rs12402181 in the seed region of miR-3117-3p, that could affect the binding with ABCC1 and RALBP1 gene, and C allele of rs7896283 in pre-mature sequence of miR-4481, which could be involved in peripheral nerve regeneration, significantly associated with VCR-induced neurotoxicity. These findings point out the possible involvement of two SNPs in miRNA associated with VCR-related neurotoxicity.

Toronto alexithymia scale for patients with eating disorder: Of performance using the non-parametric item response theory ,

BACKGROUND The aim of this study was to investigate the performance of the Toronto Alexithymia Scale (TAS-20) in patients with eating disorders. As a secondary objective, we analyzed a subset of items in order to determine whether the total score is a good tool for classifying these patients and whether the items are ordered according to the difficulty of choosing a particular answer depending on the severity of the patients condition. SUBJECTS AND METHODS We administered the TAS-20 to 103 consecutive patients who met DSM-IV-R criteria for anorexia nervosa, bulimia nervosa, or eating disorders not otherwise specified. Mokken scale analysis, nonparametric item response theory (NIRT), and confirmatory factor analysis (CFA) were used to test the psychometric properties of the scale. To improve our understanding of the structure underlying the TAS-20, we used an automated item selection procedure based on the Mokken scale. RESULTS We identified a subset of 13 independent and clinically interpretable items that are potentially sufficient to rate patients with alexithymia. This subset was considered a unidimensional reduction of the TAS-20. However, the scale composed of this subset needs to be validated. Thirteen of the 20 items were maximally related to alexithymia because they have a one-dimensional structure. The NIRT and CFA enabled us to identify a maximal subset of items that conform to the requirements for good measurement of alexithymia in patients with eating disorders.

Cognitive improvement of acetylcholinesterase inhibitors in schizophrenia

Background: Schizophrenia is a severe, persistent mental disorder, and a leading cause of disability worldwide. Cognitive impairments presented in schizophrenia lead to a worse prognostic, thus treatments targeted to enhance cognition in schizophrenia may be clinically relevant. Aims: The purpose of this study was to assess the efficacy of acetylcholinesterase inhibitors as add-on medication to antipsychotics on cognition in patients with schizophrenia. Methods: Search strategies were developed for Medline, Embase and Cochrane Central Register of Controlled Trials, and are current to March 2018. We included randomised controlled trials that compared antipsychotics plus acetylcholinesterase inhibitors versus antipsychotics plus placebo on prespecified cognitive domains (speed of processing, attention and working memory). Two review authors independently evaluated study eligibility, extracted data and assessed the risk of bias of included studies. We used random-effects model for meta-analyses and assessed the quality of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: We included nine randomised controlled trials. Six randomised controlled trials (n=219) presented evidence that acetylcholinesterase inhibitors improve speed of processing (standardised mean difference −0.52, 95% confidence interval (−0.79 to −0.25); p value=0.0002). However, eight randomised controlled trials (n=252) did find placebo was better than acetylcholinesterase inhibitors in the attention domain (−0.43, (−0.72 to −0.13); p value=0.005) and eight randomised controlled trials (n=273) did not find differences in the working memory (−0.14, (−0.51 to 0.24), p value=0.47). Conclusions: The current evidence is too weak to base recommendations on the use of acetylcholinesterase inhibitors as adjunctive treatments to antipsychotics to improve basic cognitive functions. We have limited confidence in the effect estimates.

Pharmacoepigenetics in childhood acute lymphoblastic leukemia: involvement of miRNA polymorphisms in hepatotoxicity

AIM Hepatotoxicity is one of the most common drug-related toxicities during the treatment of childhood acute lymphoblastic leukemia (ALL). Many genes involved in liver-specific signaling pathways are tightly controlled by miRNAs, and miRNA function could be modulated by SNPs. As a consequence, we hypothesized that variants in miRNAs could be associated with drug-induced hepatotoxicity. METHODS We analyzed 213 SNPs in 206 miRNAs in a cohort of 179 children with ALL homogeneously treated. RESULTS rs2648841 in miR-1208 was the most significant SNP during consolidation phase after false discovery rate correction, probably through an effect on its target genes DHFR, MTR and MTHFR. CONCLUSION These results point out the possible involvement of SNPs in miRNAs in toxicity to chemotherapy in children with ALL.

PMH52 A SHORT 12-ITEM ZARIT BURDEN INVENTORY FOR THE ASSESSMENT OF DEMENTIA CAREGIVERS AS OBTAINED BY ITEM RESPONSE THEORY

The Zarit Burden Inventory (ZBI) is a 22-item self-report scale used to assess patient’s caregiver burden on several dimensions. However, as a multidimensional instrument the clinical interpretation of its total score is sometimes unclear. Because of that, our aim in this study was to try to obtain a short-ZBI unidimensional scale based on Item Response Theory (IRT) and showing appropriate psychometric characteristics.