Effectiveness of a strategy that uses educational games to implement clinical practice guidelines among Spanish residents of family and community medicine (e-EDUCAGUIA project):A clinical trial by clusters

This study was funded by the Fondo de Investigaciones Sanitarias FIS Grant Number PI11/0477 ISCIII.-REDISSEC Proyecto RD12/0001/0012 AND FEDER Funding.Background: Clinical practice guidelines (CPGs) have been developed with the aim of helping health professionals, patients, and caregivers make decisions about their health care, using the best available evidence. In many cases, incorporation of these recommendations into clinical practice also implies a need for changes in routine clinical practice. Using educational games as a strategy for implementing recommendations among health professionals has been demonstrated to be effective in some studies; however, evidence is still scarce. The primary objective of this study is to assess the effectiveness of a teaching strategy for the implementation of CPGs using educational games (e-learning EDUCAGUIA) to improve knowledge and skills related to clinical decision-making by residents in family medicine. The primary objective will be evaluated at 1 and 6months after the intervention. The secondary objectives are to identify barriers and facilitators for the use of guidelines by residents of family medicine and to describe the educational strategies used by Spanish teaching units of family and community medicine to encourage implementation of CPGs. Methods/design: We propose a multicenter clinical trial with randomized allocation by clusters of family and community medicine teaching units in Spain. The sample size will be 394 residents (197 in each group), with the teaching units as the randomization unit and the residents comprising the analysis unit. For the intervention, both groups will receive an initial 1-h session on clinical practice guideline use and the usual dissemination strategy by e-mail. The intervention group (e-learning EDUCAGUIA) strategy will consist of educational games with hypothetical clinical scenarios in a virtual environment. The primary outcome will be the score obtained by the residents on evaluation questionnaires for each clinical practice guideline. Other included variables will be the sociodemographic and training variables of the residents and the teaching unit characteristics. The statistical analysis will consist of a descriptive analysis of variables and a baseline comparison of both groups. For the primary outcome analysis, an average score comparison of hypothetical scenario questionnaires between the EDUCAGUIA intervention group and the control group will be performed at 1 and 6months post-intervention, using 95% confidence intervals. A linear multilevel regression will be used to adjust the model. Discussion: The identification of effective teaching strategies will facilitate the incorporation of available knowledge into clinical practice that could eventually improve patient outcomes. The inclusion of information technologies as teaching tools permits greater learning autonomy and allows deeper instructor participation in the monitoring and supervision of residents. The long-term impact of this strategy is unknown; however, because it is aimed at professionals undergoing training and it addresses prevalent health problems, a small effect can be of great relevance. Trial registration: ClinicalTrials.gov: NCT02210442.Publisher PDFPeer reviewe

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

InTool Explorer: an interactive exploratory analysis tool for versatile visualizations of neuroscientific data

The bottleneck for progress in many research areas within neuroscience has shifted from the data acquisition to the data analysis stages. In the present article, we propose a method named InTool Explorer that we have developed to perform interactive exploratory data analysis, focusing on neuroanatomy as an example of its utility. This tool is freely-available software that has been designed to facilitate the study of complex neuroscience data. InTool Explorer requires no more than an internet connection and a web browser. The main contribution of this tool is to provide a user-designed canvas for data visualization and interaction, to perform specific exploratory tasks according to the user needs. Moreover, InTool Explorer permits visualization of the datasets in a very dynamic and versatile way using a linked-card approach. For this purpose, the tool allows the user to select among different predefined card types. Each card type offers an abstract data representation, a filtering tool or a set of statistical analysis methods. Additionally, InTool Explorer makes it possible linking raw images to the data. These images can be used by InTool Explorer to define new customized filtering cards. Another significant contribution of this tool is that it allows fast visualization of the data, error finding, and re-evaluation to establish new hypotheses or new lines of research. Thus, regarding its practical application in the laboratory, InTool Explorer provides a new opportunity to study and analyze neuroscience data prior to any statistical analysis being carried out

Motor neuron preservation and decrease of in vivo TDP-43 phosphorylation by protein CK-1 delta kinase inhibitor treatment

Pathogenesis of amyotrophic lateral sclerosis (ALS), a devastating disease where no treatment exists, involves the compartmentalization of the nuclear protein TDP-43 (TAR DNA-binding protein 43) in the cytoplasm which is promoted by its aberrant phosphorylation and others posttranslational modifications. Recently, it was reported that CK-1δ (protein casein kinase-1δ) is able to phosphorylate TDP-43. Here, the preclinical efficacy of a benzothiazole-based CK-1δ inhibitor IGS-2.7, both in a TDP-43 (A315T) transgenic mouse and in a human cell-based model of ALS, is shown. Treatment with IGS-2.7 produces a significant preservation of motor neurons in the anterior horn at lumbar level, a decrease in both astroglial and microglial reactivity in this area, and in TDP-43 phosphorylation in spinal cord samples. Furthermore, the recovery of TDP-43 homeostasis (phosphorylation and localization) in a human-based cell model from ALS patients after treatment with IGS-2.7 is also reported. Moreover, we have shown a trend to increase in CK-1δ mRNA in spinal cord and significantly in frontal cortex of sALS cases. All these data show for the first time the in vivo modulation of TDP-43 toxicity by CK-1δ inhibition with IGS-2.7, which may explain the benefits in the preservation of spinal motor neurons and point to the relevance of CK-1δ inhibitors in a future disease-modifying treatment for ALS.status: publishe

Pulmonary arterial enlargement predicts long-term survival in COPD patients.

Pulmonary artery enlargement (PAE) is associated with exacerbations in Chronic Obstructive Pulmonary Disease (COPD) and with survival in moderate to severe patients. The potential role of PAE in survival prediction has not been compared with other clinical and physiological prognostic markers.In 188 patients with COPD, PA diameter was measured on a chest CT and the following clinical and physiological parameters registered: age, gender, smoking status, pack-years history, dyspnea, lung function, exercise capacity, Body Mass Index, BODE index and history of exacerbations in year prior to enrolment. Proportional Cox regression analysis determined the best predictor of all cause survival.During 83 months (±42), 43 patients died. Age, pack-years history, smoking status, BMI, FEV1%, six minute walking distance, Modified Medical Research Council dyspnea scale, BODE index, exacerbation rate prior to enrollment, PA diameter and PAE (diameter≥30mm) were associated with survival. In the multivariable analysis, age (HR: 1.08; 95%CI: 1.03-1.12, p<0.001) and PAE (HR: 2.78; 95%CI: 1.35-5.75, p = 0.006) were the most powerful parameters associated with all-cause mortality.In this prospective observational study of COPD patients with mild to moderate airflow limitation, PAE was the best predictor of long-term survival along with age

Occult Hepatitis C Virus Infection in Patients with Diabetic Nephropathy: Epidemiological and Clinical Implications

Background:A high prevalence of hepatitis C virus (HCV) infection in patients with diabetic kidney disease (DKD) has been reported. However, the epidemiology and relationship between DKD and occult HCV infection (OCI)are unknown.Objetives: To determine the prevalence of OCI in a population without conventional markers of HCV infection diagnosed with DKD, and to study its possible clinical implications.Study design: This prospective study included 125 anti-HCV and serum HCV-RNA-negative patients with DKD for the presence of OCI. HCV-RNA was tested by real-time reverse transcription PCR in peripheral blood mononuclear cells and in plasma after ultracentrifugation. Results: OCI was positive in 10 patients (8%). The patients with OCI had significantly higher ferritin levels (p=.002) and monoclonal gammopathy (30% [3/10] vs. 0.87% [1/115] than the patients without OCI [p=.003]). We found similar plasma ALT and GGT levels and HbA1C in both groups. At the end of the follow-up, the progression rate of renal disease tended to be faster in the group with OCI relative to the negative one, but without a significant difference. We did not find an association between OCI and cardiovascular morbidity. nbspConclusions: There was an 8% prevalence of OCI in patients with chronic renal failure secondary to DKD, higher than in the general population. This occult infection does not appear to play a role in the control of diabetes, cardiovascular risk or steatosis. However, the progression rate of renal disease tended to be faster, and the incidence of associated monoclonal gammopathy was significant.nbs

Panel A. Univariable analysis showing the independent association of each parameter with survival.

<p>Panel B. Multivariable analysis showing those that remained in the model.</p

Association between pulmonary artery diameter and other studied variables.

<p>Association between pulmonary artery diameter and other studied variables.</p

Clinical, radiological and physiological characteristics of the patients diagnosed with and without PAE.

<p>Clinical, radiological and physiological characteristics of the patients diagnosed with and without PAE.</p

Flowchart showing the inclusion of patients for the final statistical analysis.

<p>Flowchart showing the inclusion of patients for the final statistical analysis.</p