No abstract

Introduction: Clinical practice guidelines (CPGs) are designed to improve the quality of care and reduce unjustified individual variation in clinical practice. Knowledge of the barriers and facilitators that influence the implementation of the CPG recommendations is the first step in creating strategies to improve health outcomes. The present systematic meta-review sought to explore the barriers and facilitators for the implementation of CPGs. Methods: A search was conducted in the PubMed, Embase, Cochrane, Health System Evidence and International Guideline Library (G-I-N) databases. Systematic reviews of qualitative, quantitative or mixed-methods studies that identified barriers or facilitators for the implementation of CPGs were included. The selection of the title and abstract, the evaluation of the full text, extraction of the data and the quality assessment were carried out by two independent reviewers. To summarise the evidence, we grouped the barriers and facilitators according to the following contexts: political and social, health organisational system, guidelines, health professionals and patients. Results: Overall, 25 systematic reviews were selected. The relevant barriers in the social-political context were the absence of a leader, difficulties with teamwork and a lack of agreement with colleagues. Relevant barriers in the health system were a lack of time, financial problems and a lack of specialised personnel. Barriers of the CPGs included a lack of clarity and a lack of credibility in the evidence. Regarding the health professional, a lack of knowledge about the CPG and confidence in oneself were relevant. Regarding patients, a negative attitude towards implementation, a lack of knowledge about the CPG and sociocultural beliefs played a role. Some of the most frequent facilitators were consistent leadership, commitment of the members of the team, administrative support of the institution, existence of multidisciplinary teams, application of technology to improve the practice and education regarding the guidelines. Conclusions: The barriers and facilitators described in this review are factors that influence the implementation of evidence in clinical practice. Knowledge of these factors should contribute to the development of a theoretical basis for the creation of CPG implementation strategies to improve professional practice and health outcomes for patients.

No abstract

The literature on GWAS (genome-wide association studies) data suggests that very large sample sizes (for example, 50,000 cases and 50,000 controls) may be required to detect significant associations of genomic regions for complex disorders such as Alzheimer's disease (AD). Because of the challenges of obtaining such large cohorts, we describe here a novel sequential strategy that combines pooling of DNA and bootstrapping (pbGWAS) in order to significantly increase the statistical power and exponentially reduce expenses. We applied this method to a very homogeneous sample of patients belonging to a unique and clinically well-characterized multigenerational pedigree with one of the most severe forms of early onset AD, carrying the PSEN1 p.Glu280Ala mutation (often referred to as E280A mutation), which originated as a consequence of a founder effect. In this cohort, we identified novel loci genome-wide significantly associated as modifiers of the age of onset of AD (CD44, rs187116, P = 1.29 × 10–12; NPHP1, rs10173717, P = 1.74 × 10–12; CADPS2, rs3757536, P = 1.54 × 10–10; GREM2, rs12129547, P = 1.69 × 10–13, among others) as well as other loci known to be associated with AD. Regions identified by pbGWAS were confirmed by subsequent individual genotyping. The pbGWAS methodology and the genes it targeted could provide important insights in determining the genetic causes of AD and other complex conditions.

SUMMARYGiardia intestinalis infection is prevalent throughout the world and widely distributed in developing countries. In general, children display serious consequences to their state of health, including slow height-weight development; therefore, the main aim of this study was to determine the association between Giardia infection and the nutritional status of children who participate in the program of complementary feeding (Mejoramiento Alimentario y Nutricional de Antioquia (MANA) -Instituto Colombiano de Bienestar Familiar (ICBF)). A cross-sectional study examining the association of giardiasis with nutritional status was conducted. A total of 2035 children aged eight months to six years-old were studied. Data were collected using structured questionnaires, anthropometric measurements and laboratory analysis of blood and stool samples. Analysis of the results showed that 27.6% of children were infected with G. intestinalis, while 8.1% and 1.9% were mildly and significantly underweight, respectively, and 14.1% presented stunting. Giardiasis was statistically identified as a strong predictor of stunting in this study population.

Endophenotypes are neurobiological markers cosegregating and associated with illness. These biomarkers represent a promising strategy to dissect ADHD biological causes. This study was aimed at contrasting the genetics of neuropsychological tasks for intelligence, attention, memory, visual-motor skills, and executive function in children from multigenerational and extended pedigrees that cluster ADHD in a genetic isolate. In a sample of 288 children and adolescents, 194 (67.4%) ADHD affected and 94 (32.6%) unaffected, a battery of neuropsychological tests was utilized to assess the association between genetic transmission and the ADHD phenotype. We found significant differences between affected and unaffected children in the WISC block design, PIQ and FSIQ, continuous vigilance, and visual-motor skills, and these variables exhibited a significant heritability. Given the association between these neuropsychological variables and ADHD, and also the high genetic component underlying their transmission in the studied pedigrees, we suggest that these variables be considered as potential cognitive endophenotypes suitable as quantitative trait loci (QTLs) in future studies of linkage and association.

Brain metabolites measured by 1H-MRS in the posterior cingulate gyrus and precuneus are optimally sensitive and specific potential noninvasive biomarkers of subclinical emergence of AD caused by the PSEN1 p.Glu280Ala (E280 A) mutation.

No abstract