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Value of Serum NEUROG1 Methylation for the Detection of Advanced Adenomas and Colorectal Cancer
Get PDFAberrant DNA methylation detected in liquid biopsies is a promising approach for colorectal cancer (CRC) detection, including premalignant advanced adenomas (AA). We evaluated the diagnostic capability of serum NEUROG1 methylation for the detection of AA and CRC. A CpG island in NEUROG1 promoter was assessed by bisulfite pyrosequencing in a case-control cohort to select optimal CpGs. Selected sites were evaluated through a nested methylation-specific qPCR custom assay in a screening cohort of 504 asymptomatic family-risk individuals. Individuals with no colorectal findings and benign pathologies showed low serum NEUROG1 methylation, similar to non-advanced adenomas. Contrarily, individuals bearing AA or CRC (advanced neoplasia-AN), exhibited increased NEUROG1 methylation. Using >1.3518% as NEUROG1 cut-off (90.60% specificity), 33.33% of AN and 32.08% of AA were identified, detecting 50% CRC cases. Nonetheless, the combination of NEUROG1 with fecal immunochemical test (FIT), together with age and gender through a multivariate logistic regression resulted in an AUC = 0.810 for AN, and 0.796 for AA, detecting all cancer cases and 35-47% AA (specificity 98-95%). The combination of NEUROG1 methylation with FIT, age and gender demonstrated a convenient performance for the detection of CRC and AA, providing a valuable tool for CRC screening programs in asymptomatic individuals
Proposal of a clinical care pathway for quality and safe management of headache patients: a consensus study report
Get PDFBACKGROUND: Headache is one of the most prevalent and disabling conditions. Its optimal management requires a coordinated and comprehensive response by health systems, but there is still a wide variability that compromises the quality and safety of the care process. PURPOSE: To establish the basis for designing a care pathway for headache patients through identifying key subpathways in the care process and setting out quality and clinical safety standards that contribute to providing comprehensive, adequate and safe healthcare. METHOD: A qualitative research study based on the consensus conference technique. Eleven professionals from the Spanish National Health System participated, seven of them with clinical experience in headache and four specialists in healthcare management and quality. First, identification of the key subpathways in the care process for headache, barriers/limitations for optimal quality of care, and quality and safety standards applied in each subpathway. Second, two consecutive consensus rounds were carried out to assess the content of the subpathway level descriptors, until the expert agreement was reached. Third, findings were assessed by 17 external healthcare professionals to determine their understanding, adequacy and usefulness. RESULTS: Seven key subpathways were identified: (1) primary care, (2) emergency department, (3) neurology department, (4) specialised headache unit, (5) hospitalisation, (6) outpatients and (7) governance and management. Sixty-seventh barriers were identified, the most frequent being related to diagnostic errors (36,1%), resource deficiency (25%), treatment errors (19,4%), lack of health literacy (13,9%) and inadequate communications with care transitions (5,6%). Fifty-nine quality and 31 safety standards were defined. They were related to evaluation (23.3%), patient safety (21.1%), comprehensive care (12.2%), treatment (12.2%), clinical practice guidelines (7.8%), counselling (6.7%), training (4.4%) and patient satisfaction (3.3%). CONCLUSIONS: This proposal incorporates a set of indicators and standards, which can be used to define a pathway for headache patients and determine the levels of quality
A Systematic Review of Efficacy, Safety, and Tolerability of Duloxetine
Get PDFDuloxetine is a serotonin-norepinephrine reuptake inhibitor approved for the treatment of patients affected by major depressive disorder (MDD), generalized anxiety disorder (GAD), neuropathic pain (NP), fibromyalgia (FMS), and stress incontinence urinary (SUI). These conditions share parallel pathophysiological pathways, and duloxetine treatment might be an effective and safe alternative. Thus, a systematic review was conducted following the 2009 Preferred Reporting Items (PRISMA) recommendations and Joanna Briggs Institute Critical (JBI) Appraisals guidelines. Eighty-five studies focused on efficacy, safety, and tolerability of duloxetine were included in our systematic review. Studies were subdivided by clinical condition and evaluated individually. Thus, 32 studies of MDD, 11 studies of GAD, 19 studies of NP, 9 studies of FMS, and 14 studies of SUI demonstrated that the measured outcomes indicate the suitability of duloxetine in the treatment of these clinical conditions. This systematic review confirms that the dual mechanism of duloxetine benefits the treatment of comorbid clinical conditions, and supports the efficacy, safety, and tolerability of duloxetine in short- and long-term treatments
Impact of a health alert and its implementation on flutamide prescriptions for women: an interrupted time series analysis.
Get PDFBACKGROUND: Off-label drug use among ambulatory patients is often based on little or no scientific support. This paper reports the impact of a health warning about the risks of off-label flutamide use by women and the actions subsequently implemented by the public health service targeting such use. METHOD: The study was undertaken in a region in north-west Spain. We designed a segmented regression model of an interrupted time series, in which the dependent variable was the monthly value of defined daily doses of flutamide per 1000 inhabitants/day (DDD/TID), both total and stratified by sex. The following two data sources were used: flutamide prescriptions billed to the Spanish National Health Service; and flutamide deliveries made by wholesale drug distributors to pharmacies. The intervention assessed consisted of the issue of an official health warning and the actions subsequently taken to implement it. RESULTS: There was an immediate reduction of 49.33% in DDD/TID billed to the Spanish National Health Service in respect of women; the mean value of the population percentage of DDD/TID of flutamide billed in respect of women fell from 34.4% pre-intervention to 23.72% post-intervention. There was an immediate reduction of 19.92% (95%CI: 6.68-33.15%) in total DDD/TID invoiced. There were no significant changes in DDD/TID billed in respect of men or in flutamide use in the private medical sector. CONCLUSIONS: Off-label drug misuse is a reality among ambulatory patients, even after actions are implemented following a toxicity warning issued by the competent Health Authority
Looking into the genetic bases of OCD dimensions: a pilot genome-wide association study
Get PDFThe multidimensional nature of obsessive-compulsive disorder (OCD) has been consistently reported. Clinical and biological characteristics have been associated with OCD dimensions in different ways. Studies suggest the existence of specific genetic bases for the different OCD dimensions. In this study, we analyze the genomic markers, genes, gene ontology and biological pathways associated with the presence of aggressive/checking, symmetry/order, contamination/cleaning, hoarding, and sexual/religious symptoms, as assessed via the Dimensional Yale-Brown Obsessive Compulsive Scale (DY-BOCS) in 399 probands. Logistic regression analyses were performed at the single-nucleotide polymorphism (SNP) level. Gene-based and enrichment analyses were carried out for common (SNPs) and rare variants. No SNP was associated with any dimension at a genome-wide level (p < 5 x 10(-8)). Gene-based analyses showed one gene to be associated with hoarding (SETD3, p = 1.89 x 10(-08)); a gene highly expressed in the brain and which plays a role in apoptotic processes and transcriptomic changes, and another gene associated with aggressive symptoms (CPE; p = 4.42 x 10(-6)), which is involved in neurotrophic functions and the synthesis of peptide hormones and neurotransmitters. Different pathways or biological processes were represented by genes associated with aggressive (zinc ion response and lipid metabolism), order (lipid metabolism), sexual/religious (G protein-mediated processes) and hoarding (metabolic processes and anion transport) symptoms after FDR correction; while no pathway was associated with contamination. Specific genomic bases were found for each dimension assessed, especially in the enrichment analyses. Further research with larger samples and different techniques, such as next-generation sequencing, are needed to better understand the differential genetics of OCD dimensions
Haplotype analysis of the internationally distributed BRCA1 c.3331_3334delCAAG founder mutation reveals a common ancestral origin in Iberia
Get PDFBACKGROUND: The BRCA1 c.3331_3334delCAAG founder mutation has been reported in hereditary breast and ovarian cancer families from multiple Hispanic groups. We aimed to evaluate BRCA1 c.3331_3334delCAAG haplotype diversity in cases of European, African, and Latin American ancestry. METHODS: BC mutation carrier cases from Colombia (n = 32), Spain (n = 13), Portugal (n = 2), Chile (n = 10), Africa (n = 1), and Brazil (n = 2) were genotyped with the genome-wide single nucleotide polymorphism (SNP) arrays to evaluate haplotype diversity around BRCA1 c.3331_3334delCAAG. Additional Portuguese (n = 13) and Brazilian (n = 18) BC mutation carriers were genotyped for 15 informative SNPs surrounding BRCA1. Data were phased using SHAPEIT2, and identical by descent regions were determined using BEAGLE and GERMLINE. DMLE+ was used to date the mutation in Colombia and Iberia. RESULTS: The haplotype reconstruction revealed a shared 264.4-kb region among carriers from all six countries. The estimated mutation age was ~ 100 generations in Iberia and that it was introduced to South America early during the European colonization period. CONCLUSIONS: Our results suggest that this mutation originated in Iberia and later introduced to Colombia and South America at the time of Spanish colonization during the early 1500s. We also found that the Colombian mutation carriers had higher European ancestry, at the BRCA1 gene harboring chromosome 17, than controls, which further supported the European origin of the mutation. Understanding founder mutations in diverse populations has implications in implementing cost-effective, ancestry-informed screening
Systematic meta-analyses, field synopsis and global assessment of the evidence of genetic association studies in colorectal cancer
Get PDFOBJECTIVE: To provide an understanding of the role of common genetic variations in colorectal cancer (CRC) risk, we report an updated field synopsis and comprehensive assessment of evidence to catalogue all genetic markers for CRC (CRCgene2). DESIGN: We included 869 publications after parallel literature review and extracted data for 1063 polymorphisms in 303 different genes. Meta-analyses were performed for 308 single nucleotide polymorphisms (SNPs) in 158 different genes with at least three independent studies available for analysis. Scottish, Canadian and Spanish data from genome-wide association studies (GWASs) were incorporated for the meta-analyses of 132 SNPs. To assess and classify the credibility of the associations, we applied the Venice criteria and Bayesian False-Discovery Probability (BFDP). Genetic associations classified as 'positive' and 'less-credible positive' were further validated in three large GWAS consortia conducted in populations of European origin. RESULTS: We initially identified 18 independent variants at 16 loci that were classified as 'positive' polymorphisms for their highly credible associations with CRC risk and 59 variants at 49 loci that were classified as 'less-credible positive' SNPs; 72.2% of the 'positive' SNPs were successfully replicated in three large GWASs and the ones that were not replicated were downgraded to 'less-credible' positive (reducing the 'positive' variants to 14 at 11 loci). For the remaining 231 variants, which were previously reported, our meta-analyses found no evidence to support their associations with CRC risk. CONCLUSION: The CRCgene2 database provides an updated list of genetic variants related to CRC risk by using harmonised methods to assess their credibility
Cribado neonatal de la inmunodeficiencia combinada grave: análisis coste-efectividad
No full textLos objetivos principales de este documento son: Informar sobre los estudios de coste-efectividad del cribado neonatal de la IDCG identificados tras la revisión sistemática de la literatura; y evaluar el coste-efectividad del cribado neonatal de la IDCG desde la perspectiva del SNS en España
Lanzar una búsqueda en Mergullador desde fuera de la institución.III
No full textMergullador4El vídeo explica cómo se puede realizar una búsqueda en Mergullador a los usuarios de Bibliosaúde cuando están fuera de la institución
Localizar un articulo por doi en Mergullador
No full textMergullador5El vídeo describe como buscar en Mergullador por DO