Breast cancer PAM50 signature: correlation and concordance between RNA-Seq and digital multiplexed gene expression technologies in a triple negative breast cancer series.

BACKGROUND: Full RNA-Seq is a fundamental research tool for whole transcriptome analysis. However, it is too costly and time consuming to be used in routine clinical practice. We evaluated the transcript quantification agreement between RNA-Seq and a digital multiplexed gene expression platform, and the subtype call after running the PAM50 assay in a series of breast cancer patients classified as triple negative by IHC/FISH. The goal of this study is to analyze the concordance between both expression platforms overall, and for calling PAM50 triple negative breast cancer intrinsic subtypes in particular. RESULTS: The analyses were performed in paraffin-embedded tissues from 96 patients recruited in a multicenter, prospective, non-randomized neoadjuvant triple negative breast cancer trial (NCT01560663). Pre-treatment core biopsies were obtained following clinical practice guidelines and conserved as FFPE for further RNA extraction. PAM50 was performed on both digital multiplexed gene expression and RNA-Seq platforms. Subtype assignment was based on the nearest centroid classification following this procedure for both platforms and it was concordant on 96% of the cases (N = 96). In four cases, digital multiplexed gene expression analysis and RNA-Seq were discordant. The Spearman correlation to each of the centroids and the risk of recurrence were above 0.89 in both platforms while the agreement on Proliferation Score reached up to 0.97. In addition, 82% of the individual PAM50 genes showed a correlation coefficient > 0.80. CONCLUSIONS: In our analysis, the subtype calling in most of the samples was concordant in both platforms and the potential discordances had reduced clinical implications in terms of prognosis. If speed and cost are the main driving forces then the preferred technique is the digital multiplexed platform, while if whole genome patterns and subtype are the driving forces, then RNA-Seq is the preferred method.

Impact of the intellectual disability severity in the Spanish Personal Outcomes Scale.

BACKGROUND: The interest in measuring quality of life (QoL) in persons with intellectual disability (ID) has brought about a number of QoL measurements for this population. These measurements need to address two issues that have contributed to enhancing the current instruments. First, the necessity to develop measures with adequate psychometric properties, which has been discussed in recent studies, and second, the agreement between experts in analysing objective and subjective perspectives, as well as the use of self-report to include the participation of the person with ID. The question that we set out to investigate in this paper is whether the measurements function properly for the person with ID, independent of their level of severity. We used the Spanish version of the Personal Outcomes Scale, as it is a psychometrically sound instrument and includes three sources of information (the person with ID, a professional and a family member). METHOD: The sample was composed of 529 persons with ID (296 men, representing 55.95% of the total sample, and 233 women, with Mage  = 35.03, SD = 10.82) from several regions of Spain, along with their professional of reference and a family member. The severity variable was estimated for each item based on estimations of differential item functioning. RESULTS: The results showed that several items were undervalued by the assessments if the severity of the ID was greater. Mainly, this difference was observed in the assessments by professionals and in the dimensions of rights, personal development and self-determination. CONCLUSIONS: This paper focuses on the uses and interpretations of the results of the QoL measurements in the Personal Outcomes Scale. The results indicate that, in our sample, when people with high levels of ID are assessed, the functioning of some items are affected by the severity of this disability. For correct use, these items must be interpreted on the basis of the results obtained. Additionally, it is necessary to thoroughly review the QoL indicators for persons with severe or profound ID.

Item response theory analysis applied to the Spanish version of the Personal Outcomes Scale.

BACKGROUND: The study of measurements of quality of life (QoL) is one of the great challenges of modern psychology and psychometric approaches. This issue has greater importance when examining QoL in populations that were historically treated on the basis of their deficiency, and recently, the focus has shifted to what each person values and desires in their life, as in cases of people with intellectual disability (ID). Many studies of QoL scales applied in this area have attempted to improve the validity and reliability of their components by incorporating various sources of information to achieve consistency in the data obtained. The adaptation of the Personal Outcomes Scale (POS) in Spanish has shown excellent psychometric attributes, and its administration has three sources of information: self-assessment, practitioner and family. The study of possible congruence or incongruence of observed distributions of each item between sources is therefore essential to ensure a correct interpretation of the measure. The aim of this paper was to analyse the observed distribution of items and dimensions from the three Spanish POS information sources cited earlier, using the item response theory. METHOD: We studied a sample of 529 people with ID and their respective practitioners and family member, and in each case, we analysed items and factors using Samejima's model of polytomic ordinal scales. RESULTS: The results indicated an important number of items with differential effects regarding sources, and in some cases, they indicated significant differences in the distribution of items, factors and sources of information. CONCLUSIONS: As a result of this analysis, we must affirm that the administration of the POS, considering three sources of information, was adequate overall, but a correct interpretation of the results requires that it obtain much more information to consider, as well as some specific items in specific dimensions. The overall ratings, if these comments are considered, could result in bias.

[Use of benzodiazepines in prolonged seizures and status epilepticus in the community]. / Uso benzodiacepinas en crisis prolongadas y estado epiléptico en la comunidad.

Prolonged seizures and status epilepticus are common neurological medical emergencies. Early and appropriate treatment is essential to reduce morbidity and mortality. Most seizures occur in the community, so parents and caregivers must be prepared for their management. Benzodiazepines (BZD) are the first-line drugs used, with rectal diazepam (DZPr) being the most commonly used in pre-hospital treatment in Spain. In September 2011, the European Medicines Agency (EMA) authorized the use of oromucosal midazolam (MDZb) for the treatment of prolonged acute convulsive seizures in patients aged 3 months to <18 years. MDZb has a rapid onset, short duration of effect, and avoids first-pass hepatic metabolism. MDZb has shown to be at least as or more effective than DZPr to stop the seizures. Buccal administration is easier and more socially accepted, especially in adolescents and adults. It is a safe drug with similar effects to other BZD; MDZb improves the overall cost-effectiveness of seizures management.

[Cost-effectiveness of buccal midazolam in the treatment of prolonged convulsive seizures in the outpatient setting in Spain]. / Coste-efectividad de una solucion bucal de midazolam en el tratamiento de las crisis convulsivas prolongadas en el entorno ambulatorio en España.

INTRODUCTION: To be able to treat prolonged epileptic crises practical, safe and effective rescue medication is needed. Today, the standard treatment in community healthcare is rectal diazepam. The introduction of a buccal solution of midazolam opens up a new perspective in their treatment. AIMS: To evaluate the cost-effectiveness of buccal midazolam with respect to rectal diazepam for children diagnosed with epilepsy who present prolonged convulsive seizures in the community setting in Spain. MATERIALS AND METHODS: The study produces a model of its cost-effectiveness from the perspective of the Spanish National Health System (SNS), with the outcomes presented in terms of cost-quality adjusted life years. Data were collected from different sources, including estimations regarding the clinical effectiveness from a clinical trial, from a Delphi panel in Spain and from a national survey carried out on parents of children with epilepsy in order to determine the current practices. RESULTS: Treatment with buccal midazolam produces a saving in costs in comparison to rectal diazepam. The amount saved by the Spanish SNS comes to 5,484 euros per patient per year. Treatment with buccal midazolam offers an improved health-related quality of life. This, together with the savings in costs, means that there is a dominance of buccal midazolam over rectal diazepam in all the settings that have been examined. CONCLUSIONS: The results obtained with the model show that buccal midazolam is more cost-effective than rectal diazepam due to a reduction in the need to call out ambulances and for stays in hospital, as well as an improved health-related quality of life.

TITLE: Coste-efectividad de una solucion bucal de midazolam en el tratamiento de las crisis convulsivas prolongadas en el entorno ambulatorio en España.Introduccion. El tratamiento de las crisis epilepticas prolongadas requiere disponer de una medicacion de rescate comoda, segura y efectiva. Actualmente, el tratamiento estandar en la comunidad es el diacepam rectal. La introduccion de una solucion bucal de midazolam abre una perspectiva nueva en el tratamiento. Objetivo. Evaluar el coste-efectividad del midazolam bucal respecto al diacepam rectal para los niños con un diagnostico de epilepsia que presentan crisis convulsivas prolongadas en la comunidad en España. Materiales y metodos. Modelo coste-efectividad desde la perspectiva del Sistema Nacional de Salud (SNS) español, con resultados presentados en terminos de costes y años de vida ajustados por calidad. Los datos se obtuvieron de varias fuentes, incluidas las estimaciones de efectividad clinica de un ensayo clinico, de un panel Delphi en España y de una encuesta nacional a padres de niños con epilepsia para determinar las practicas actuales. Resultados. El tratamiento con midazolam bucal produce un ahorro de costes en comparacion con el diacepam rectal. El ahorro para el SNS español es de 5.484 euros por paciente al año. El tratamiento con midazolam bucal ofrece una mejora en la calidad de vida relacionada con la salud. Esto, unido al ahorro de costes, hace que el midazolam bucal sea dominante frente al diacepam rectal en todos los escenarios examinados. Conclusion. Los resultados del modelo muestran que el midazolam bucal es mas coste-efectivo que el diacepam rectal debido a una reduccion en la necesidad de llamadas a la ambulancia y estancias en el hospital, asi como a una mejora en la calidad de vida relacionada con la salud.

Pericardial tamponade in a patient with polymyalgia rheumatica.

We report a patient who developed pericarditis and pericardial tamponade coinciding with polymyalgia rheumatica onset. Our patient did not show any clinical sign of vasculitis; temporal artery biopsies were negative for giant cell arteritis. Pericardial biopsy in our case shows inflammatory perivascular lymphocytary infiltrates thus we believe pericardial effusion has an inflammatory-immunologic origin. Cardiac manifestations are exceptional in polymyalgia rheumatica, though it should be considered in the differential diagnosis in patients with pericarditis over 50 years. The recognition of this uncommon manifestation is very important due to the good response to corticosteroid treatment.

Factor structure of Eating Disorders Inventory-2 in a Spanish sample.

OBJECTIVE: To present basic statistics and analyze factor structure of EDI-2 in an adolescent non-clinical sample from Spain. METHOD: An Exploratory Factor Analysis (EFA) was carried out with Principal Axis Factoring (PAF) and oblimin rotation, using raw scores. RESULTS: EFA presented a 21-factor structure with eigenvalues greater than 1. It was then forced into 11 and 5-factor solutions. DISCUSSION: The eleven-factor structure does not correspond with the 11 scales. A five-factor structure seems to be better suited than other factor solutions and presented higher reliability coefficients.