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Doñinos de Salamanca, Spain

Alaka K.J.,Eli Lilly and Company | Noble W.,inVentiv Health | Montejo A.,University of Salamanca | Montejo A.,Institute Investigacion Biomedica Of Salamanca | And 7 more authors.
International Journal of Geriatric Psychiatry | Year: 2014

Objective This was a flexible-dosed study to evaluate the efficacy and safety of duloxetine 30-120 mg once daily in the treatment of generalized anxiety disorder (GAD) in older adult patients. Methods Patients with GAD, who were at least 65 years of age, were randomly assigned to double-blind treatment with either duloxetine (N = 151) or placebo (N = 140). The primary efficacy measure was the Hamilton Anxiety Rating Scale (HAM-A) total score, and the primary endpoint was at week 10. Global functioning was assessed by the Sheehan Disability Scale (SDS). Safety and tolerability was assessed by the occurrence of treatment-emergent adverse events, serious adverse events, laboratory analyses, and vital signs. Analyses were conducted on an intent-to-treat basis. Results The overall baseline mean HAM-A total score was 24, and SDS global score was 14. Completion rates were 75% for placebo and 76% for duloxetine. At week 10, duloxetine was superior to placebo on mean changes from baseline in HAM-A total scores (-15.9 vs. -11.7, p < 0.001) and in SDS global scores (-8.6 vs. -5.4, p < 0.001). Treatment-emergent adverse events occurred in ≥5% of duloxetine-treated patients and twice the rate than with placebo including constipation (9% vs. 4%, p = 0.06), dry mouth (7% vs. 1%, p = 0.02), and somnolence (6% vs. 2%, p = 0.14). Conclusion Duloxetine treatment was efficacious in the improvement of anxiety and functioning in older adult patients with GAD, and the safety profile was consistent with previous GAD studies. © 2014 John Wiley & Sons, Ltd.

Albagha O.M.E.,University of Edinburgh | Visconti M.R.,University of Edinburgh | Alonso N.,University of Edinburgh | Wani S.,University of Edinburgh | And 21 more authors.
Journal of Bone and Mineral Research | Year: 2013

Paget's disease of bone (PDB) has a strong genetic component. Here, we investigated possible associations between genetic variants that predispose to PDB and disease severity. Allelic variants identified as predictors of PDB from genome-wide association studies were analyzed in 1940 PDB patients from the United Kingdom, Italy, Western Australia, and Spain. A cumulative risk allele score was constructed by adding the variants together and relating this to markers of disease severity, alone and in combination with SQSTM1 mutations. In SQSTM1-negative patients, risk allele scores in the highest tertile were associated with a 27% increase in disease extent compared with the lowest tertile (p < 0.00001) with intermediate values in the middle tertile (20% increase; p = 0.0007). The effects were similar for disease severity score, which was 15% (p = 0.01) and 25% (p < 0.00001) higher in the middle and upper tertiles, respectively. Risk allele score remained a significant predictor of extent and severity when SQSTM-positive individuals were included, with an effect size approximately one-third of that observed with SQSTM1 mutations. A genetic risk score was developed by combining information from both markers, which identified subgroups of individuals with low, medium, and high levels of severity with a specificity of 70% and sensitivity of 55%. Risk allele scores and SQSTM1 mutations both predict extent and severity of PDB. It is possible that with further refinement, genetic profiling may be of clinical value in identifying individuals at high risk of severe disease who might benefit from enhanced surveillance and early intervention. © 2013 American Society for Bone and Mineral Research.

Corral-Gudino L.,Servicio de Medicina Interna | Corral-Gudino L.,Institute Investigacion Biomedica Of Salamanca | Borao-Cengotita-Bengoa M.,Medicine of the Elderly and Acute Medicine | Del Pino-Montes J.,Institute Investigacion Biomedica Of Salamanca | And 2 more authors.
Bone | Year: 2013

Context: Several studies have suggested that the prevalence and severity of PDB have fallen in recent years. The magnitude of this trend and its globalization have not been well established. Objective: The objective of this study is to estimate the pooled magnitude of the changes in the prevalence of PDB and as a secondary objective, to make up a world atlas of PDB prevalence. Methods: A systematic review of English and non-English articles using MEDLINE (1946 to 2013) and EMBASE (1980 to 2013) was the method used. Search terms included epidemiology, incidence, prevalence, cohort studies, osteitis deformans or Paget's disease of bone. Studies with incidence and/or prevalence rate for PDB were included. Two authors independently extracted the data using predefined data fields and quality assessment. A pooled analysis based on random-effects models was carried out for secular trends. Results: Twenty-eight articles documented the prevalence of PDB; four articles the incidence and two articles the rate of new referrals. The prevalence of PDB varied greatly between the different countries, from 0.00028% in Japan to 5.4% in the UK. There were available data on changes in prevalence from two different surveys over two different time frames in Europe and New Zealand. In all but one city (Turin), a drop in the prevalence of PDB was recorded (pooled OR 0.64; 95% CI 0.45-0.91). Conclusion: The incidence and prevalence rates of PDB vary widely between populations but both have decreased in most regions over recent years. The changes are heterogeneous however and within countries, the largest changes have been in areas that previously had a high prevalence. The reasons for these changes remain unclear at present but are likely to be due to an interaction between genetic factors and environmental triggers which may differ in different regions. © 2013 Elsevier Inc.

Del Rey M.,University of Salamanca | Del Rey M.,Institute Investigacion Biomedica Of Salamanca | Benito R.,University of Salamanca | Benito R.,Institute Investigacion Biomedica Of Salamanca | And 20 more authors.
PLoS ONE | Year: 2015

The presence of SF3B1 gene mutations is a hallmark of refractory anemia with ring sideroblasts (RARS). However, the mechanisms responsible for iron accumulation that characterize the Myelodysplastic Syndrome with ring sideroblasts (MDS-RS) are not completely understood. In order to gain insight in the molecular basis of MDS-RS, an integrative study of the expression and mutational status of genes related to iron and mitochondrial metabolism was carried out. A total of 231 low-risk MDS patients and 81 controls were studied. Gene expression analysis revealed that iron metabolism and mitochondrial function had the highest number of genes deregulated in RARS patients compared to controls and the refractory cytopenias with unilineage dysplasia (RCUD). Thus mitochondrial transporters SLC25 (SLC25A37 and SLC25A38) and ALAD genes were over-expressed in RARS. Moreover, significant differences were observed between patients with SF3B1 mutations and patients without the mutations. The deregulation of genes involved in iron and mitochondrial metabolism provides new insights in our knowledge of MDS-RS. New variants that could be involved in the pathogenesis of these diseases have been identified. copy; 2015 del Rey et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

del Rey M.,University of Salamanca | del Rey M.,Institute Investigacion Biomedica Of Salamanca | Pericacho M.,Institute Investigacion Biomedica Of Salamanca | Pericacho M.,University of Salamanca | And 10 more authors.
PLoS ONE | Year: 2013

The functional mechanisms involved in angiogenesis and the potential role of endoglin (ENG), recently described as a new marker for this process, have not been explored in Myelodysplastic Syndromes (MDS). In order to gain insight in MDS angiogenesis a combined analysis in bone marrow (BM) of gene expression levels, angiogenesis-related soluble factors and functional angiogenesis-related studies was carried out. Ninety-seven MDS patients and forty-two normal BM samples were studied. The morphology of the capillary-like structures originated by two endothelial cells lines in the BM environment of patients with refractory cytopenia with multilineage dysplasia (RCMD) was different from those of the remaining MDS. In addition, the BM mononuclear cells from RCMD patients displayed over-expression of VEGF, HIF and FN1 while they showed reduced expression of ENG in contrast to the normal ENG expression of the remaining low-risk MDS and the high expression of ENG in high-risk MDS subtype. Moreover, higher soluble ENG and soluble FLT-1 levels in BM microenvironment were observed in RCMD cases, which distinguished them from other individuals. Therefore, the present study suggests that the patterns of angiogenesis are different between the MDS subtypes. The differences in angiogenesis observed in RCMD patients could be related to ENG abnormalities. © 2013 del Rey et al.

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