Institute Municipal dInvestigacio Medica

Barcelona, Spain

Institute Municipal dInvestigacio Medica

Barcelona, Spain
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Gonzalez-Macias J.,University of Cantabria | Gonzalez-Macias J.,Charles III University of Madrid | Vila J.,Institute Municipal dInvestigacio Medica | Diez-Perez A.,Charles III University of Madrid | Diez-Perez A.,Autonomous University of Barcelona
Bone | Year: 2012

Purpose: To assess the ability of the Spanish version of the WHO fracture risk assessment tool (FRAX®) to predict the observed incident fractures in the ECOSAP Study cohort. Methods: 5201 women, aged 65 or older, were enrolled in a three-year, prospective study by a non-randomized sampling of consecutive cases in 58 primary care centers in Spain. Participants completed an osteoporosis and fracture risk questionnaire and attended follow-up visits every 6. months. All radiologically or surgically confirmed low-trauma, non-spinal fractures were collected. The individual 10-year absolute risks of hip and major osteoporotic fractures were calculated with the FRAX® algorithms for Spain without the inclusion of the bone mineral density (BMD) measurements. Calibration was evaluated by comparing the three-year estimated (E) fractures predicted with FRAX® with the number of observed (O) fractures, and their discriminative ability for the probability of new fractures with the area under the receiving operating characteristic (ROC) curves. Results: Fifty (0.96%) women sustained an incident hip fracture, and 201 (3.81%) women presented with major osteoporotic fractures (hip, forearm or humerus). The E/O ratios for hip and major osteoporotic fractures were 1.10 and 0.66 respectively. Clinical vertebral fractures were not collected; therefore, the E/O ratio for major fractures should be expected to be lower. The difference between E and O cases reached statistical significance (χ 2, p<0.001). Areas under the ROC curves were 0.640 and 0.615 for hip and major osteoporotic fractures respectively. Conclusions: The Spanish FRAX® underestimates the risk for major osteoporotic fractures. The estimated risk for hip fractures was similar to the observed fractures; however the algorithm had only modest discriminative ability. These results should be interpreted in the context of the relatively low number of observed fractures, especially at the hip. © 2011 Elsevier Inc.


Karakosta P.,University of Crete | Alegakis D.,University of Crete | Georgiou V.,University of Crete | Roumeliotaki T.,University of Crete | And 8 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Context: Maternal thyroid dysfunction, especially in early pregnancy, may lead to pregnancy complications and adverse birth outcomes. Few population-based prospective studies have evaluated these effects and results are discrepant. Objective: We examined the association of thyroid function and autoimmunity in early pregnancy with adverse pregnancy and birth outcomes. Setting and Participants: The study used data from the prospective mother-child cohort "Rhea" study in Crete, Greece. A total of 1170 women with singleton pregnancies participated in this analysis. Maternal serum samples in the first trimester of pregnancy were tested for thyroidhormones (TSH, free T4, and free T3) and thyroid antibodies (thyroid peroxidase antibody and thyroglobulin antibody). Multivariable log-Poisson regression models were used adjusting for confounders. Main Outcome Measures: Outcomes included gestational diabetes, gestational hypertension/preeclampsia, cesarean section, preterm delivery, low birth weight, and small-for-gestational-age neonates. Results: The combination of high TSH and thyroid autoimmunity in early pregnancy was associated with a 4-fold increased risk for gestational diabetes [relative risk (RR) 4.3, 95% confidence interval (CI) 2.1- 8.9)] and a 3-fold increased risk for low birth weight neonates (RR 3.1,95%CI 1.2- 8.0) after adjustment for several confounders. Women positive for thyroid antibodies without elevated TSH levels in early pregnancy were at high risk for spontaneous preterm delivery (RR 1.7, 95% CI 1.1-2.8), whereas the combined effect of high TSH and positive thyroid antibodies did not show an association with preterm birth. Conclusions: High TSH levels and thyroid autoimmunity in early pregnancy may detrimentally affect pregnancy and birth outcomes. Copyright © 2012 by The Endocrine Society.


Sanchez-Benavides G.,Institute Municipal dInvestigacio Medica | Sanchez-Benavides G.,Autonomous University of Barcelona | Gomez-Anson B.,Hospital Of La Santa Creu I Sant Pau | Sainz A.,Autonomous University of Barcelona | And 4 more authors.
Psychiatry Research - Neuroimaging | Year: 2010

Hippocampal volume is reduced in Alzheimer Disease (AD) and has been proposed as a possible surrogate biomarker to aid early diagnosis. Whilst automated methods to segment the hippocampus from magnetic resonance images are available, manual segmentation, in spite of being time-consuming and unsuitable for large samples, is still the standard. In order to study the validity of FreeSurfer's automated method, we compared hippocampal automated measures with manual tracing in a sample composed of healthy elderly (N = 41), Mild Cognitive Impairment (MCI) (N = 23), and AD (N = 25) subjects. Percent volume overlap, percent volume difference, correlations, and Bland-Altman plots were studied. Automated measures were slightly larger than hand tracing ones (mean difference 10%). Percent volume overlap showed good results, but was far from perfect (78%). Manual and automated volume correlations were approximately 0.84 and the Bland-Altman analysis showed acceptable interchangeability of methods. Within-group analysis demonstrated that patient samples obtained smaller values in validity indexes than controls. Globally, FreeSurfer's automated hippocampal volumetry showed adequate validity when compared to manual tracing, with a tendency to overestimation. Nevertheless, the greater difference between automated and manual segmentation in atrophic brains suggests that studies in AD based on this software could be more likely to produce false negatives. © 2009 Elsevier Ireland Ltd. All rights reserved.


Van Arensbergen J.,Institute dInvestigacions Biomediques August Pi i Sunyer | Van Arensbergen J.,CIBER ISCIII | Garcia-Hurtado J.,Institute dInvestigacions Biomediques August Pi i Sunyer | Garcia-Hurtado J.,CIBER ISCIII | And 11 more authors.
Genome Research | Year: 2010

The epigenome changes that underlie cellular differentiation in developing organisms are poorly understood. To gain insights into how pancreatic beta-cells are programmed, we profiled key histone methylations and transcripts in embryonic stem cells, multipotent progenitors of the nascent embryonic pancreas, purified beta-cells, and 10 differentiated tissues. We report that despite their endodermal origin, beta-cells show a transcriptional and active chromatin signature that is most similar to ectoderm-derived neural tissues. In contrast, the beta-cell signature of trimethylated H3K27, a mark of Polycomb-mediated repression, clusters with pancreatic progenitors, acinar cells and liver, consistent with the epigenetic transmission of this mark from endoderm progenitors to their differentiated cellular progeny. We also identified two H3K27 methylation events that arise in the beta-cell lineage after the pancreatic progenitor stage. One is a wave of cell-selective de novo H3K27 trimethylation in non-CpG island genes. Another is the loss of bivalent and H3K27me3-repressed chromatin in a core program of neural developmental regulators that enables a convergence of the gene activity state of beta-cells with that of neural cells. These findings reveal a dynamic regulation of Polycomb repression programs that shape the identity of differentiated beta-cells. © 2010 by Cold Spring Harbor Laboratory Press.


Garcia A.M.,University of Valencia | Garcia A.M.,CIBER ISCIII | Ramon-Bou N.,Conselleria de Sanidad | Porta M.,CIBER ISCIII | And 2 more authors.
Journal of Alzheimer's Disease | Year: 2010

The roles of smoking and alcohol on the development of Alzheimer's disease (AD) remain unclear. We performed a case-control study on the effects of both exposures before the age of onset of the disease in the cases (and same reference age for their age-matched controls) on disease risk. Interviews were conducted with population controls (n=246) and relatives of cases (n=176) identified through local Alzheimer's Disease Associations. Logistic regression models were built adjusting by gender, age, residence, education, economic situation, employment, and history of dementia in close relatives. Risk of AD was unaffected by any measure of tobacco consumption. Alcohol consumers showed a lower risk of AD than never consumers (adjusted odds ratio, aOR = 0.53, 95% CI 0.32, 0.88), with differences by gender (women aOR =0.48, 95% CI 0.27, 0.84; men aOR=0.80, 95% CI 0.23, 2.80). Mean daily total consumption of alcohol and time consuming alcohol showed increasingly protective dose-response relationships in women. Lower AD risk was observed in alcohol drinkers of both genders who never smoked (aOR= 0.37, 95% CI 0.21, 0.65). All these associations were independent of the presence of apolipoprotein E4 allele(s) in the cases. Although the sample was small for some analyses addressing these interactions, our results suggest a protective effect of alcohol consumption, mostly in non-smokers, and the need to consider interactions between tobacco and alcohol consumption, as well as interactions with gender, when assessing the effects of smoking and/or drinking on the risk of AD. © 2010 - IOS Press and the authors. All rights reserved.


Lopez-Aguila S.,Agencia dInformacio | Lopez-Aguila S.,Research Center Biomedica En Red Of Epidemiologia lud Publica | Contel J.C.,DAP Costa Ponent | Farre J.,SAP | And 4 more authors.
American Journal of Managed Care | Year: 2011

Objectives: To study risk factors for and likelihood of unplanned hospital admission and readmission in persons aged ≥65 years in Catalonia, Spain. Study Design: Retrospective cohort study. Methods: We used data from clinical records of the primary care centers, pharmacy database, and hospital discharge records for persons aged ≥65 years registered in primary care centers of referral hospitals in the Baix Llobregat healthcare area. Unplanned hospital admission was defined as any unscheduled hospitalization in 2008; unplanned readmission was defined as any unscheduled admission occurring within 6 months after discharge date of index admission. Logistic regression analysis was used to identify predictors of unplanned hospital admission and readmission. Results: The population included 28,430 individuals. Among them, 2103 (7%) experienced an unplanned admission and 365 (1.3%) an unplanned readmission. The readmission rate for the admitted population was 18.7%. The strongest predictive factor of unplanned admission was ≥2 admissions in the previous 2 years (odds ratio [OR] 24.9, 95% confidence interval [CI] 16.0-38.7 for 2007; OR 15.6, 95% CI 8.6-28.0 for 2006). Factors associated with unplanned readmission were aged ≥80 years (OR 4.6, 95% CI 3.1-7.1) and ≥2 admissions during the previous year (OR 20.4, 95% CI 14.1-29.5). The area under the receiver operating characteristics curve was 0.78 for unplanned admission and 0.85 for unplanned readmission in the development sample and 0.76 and 0.81, respectively, in the validation sample. Conclusions: Aged persons and those who used more hospital services in previous years had a higher probability of hospital admission and readmission.


Diaz-Lopez A.,Institute dInvestigacio Sanitaria Pere Virgili | Diaz-Lopez A.,CIBER ISCIII | Bullo M.,Institute dInvestigacio Sanitaria Pere Virgili | Bullo M.,CIBER ISCIII | And 11 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Context and Objective: Because it has been suggested that osteocalcin (OC), an osteoblast-derived hormone, is a new link between bone and glucose metabolism, we tested whether serum carboxylated osteocalcin (cOC) and undercarboxylated osteocalcin (ucOC) levels are independently associated with the development of type 2 diabetes in subjects at high cardiovascular risk. Design, Setting, and Participants: A prospective, nested case-control study was conducted using datafromthe Prevención con Dieta Mediterrá nea(PREDIMED)study.Weincluded 153 case subjects with newly diagnosed diabetes and 306 individually matched control subjects free of diabetes identified during a mean 5-year follow-up. Conditional logistic regression models were used to estimate matched odds ratios for incident diabetes according to categories of both forms of OC measured by ELISAs. Results: Baseline serum concentrations of both forms ofOCwere significantly lower in case subjects than in control subjects. In subjects with incident cases of diabetes, concentrations of cOC, but not of ucOC, were inversely and significantly associated with homeostasis model assessment of insulin resistance levels (β = -0.335) and with fasting glucose concentrations (β = -0.044) in control subjects, independent of other relevant confounders. In the conditional logistic model that took into account the matching factors, the odds ratios for diabetes incidence in the lowest vs the highest tertile of cOC and ucOC were 2.03 (95% confidence interval, 1.32-3.13) and 1.88 (1.23- 2.85), respectively. Further adjustment for family history of diabetes, lifestyle, and other confounding factors did not appreciably change the magnitude of these associations. Conclusion: In a population at high cardiovascular risk, low concentrations of serum cOC and ucOC were strongly associated with an increased risk of incident diabetes. Copyright © 2013 by The Endocrine Society.


Pellegrinet L.,Ecole Polytechnique Federale de Lausanne | Rodilla V.,Institute Municipal dInvestigacio Medica | Liu Z.,University of Washington | Chen S.,University of Washington | And 6 more authors.
Gastroenterology | Year: 2011

Background & Aims: Ablation of Notch signaling within the intestinal epithelium results in loss of proliferating crypt progenitors due to their conversion into postmitotic secretory cells. We aimed to confirm that Notch was active in stem cells (SCs), investigate consequences of loss of Notch signaling within the intestinal SC compartment, and identify the physiologic ligands of Notch in mouse intestine. Furthermore, we investigated whether the induction of goblet cell differentiation that results from loss of Notch requires the transcription factor Krppel-like factor 4 (Klf4). Methods: Transgenic mice that carried a reporter of Notch1 activation were used for lineage tracing experiments. The in vivo functions of the Notch ligands Jagged1 (Jag1), Delta-like1 (Dll1), Delta-like4 (Dll4), and the transcription factor Klf4 were assessed in mice with inducible, gut-specific gene targeting (Vil-Cre-ER T2). Results: Notch1 signaling was found to be activated in intestinal SCs. Although deletion of Jag1 or Dll4 did not perturb the intestinal epithelium, inactivation of Dll1 resulted in a moderate increase in number of goblet cells without noticeable effects of progenitor proliferation. However, simultaneous inactivation of Dll1 and Dll4 resulted in the complete conversion of proliferating progenitors into postmitotic goblet cells, concomitant with loss of SCs (Olfm4+, Lgr5+, and Ascl2+). Klf4 inactivation did not interfere with goblet cell differentiation in adult wild-type or in Notch pathwaydeficient gut. Conclusions: Notch signaling in SCs and progenitors is activated by Dll1 and Dll4 ligands and is required for maintenance of intestinal progenitor and SCs. Klf4 is dispensable for goblet cell differentiation in intestines of adult Notch-deficient mice. © 2011 AGA Institute.


Sitges-Serra A.,Endocrine Surgery Unit | Garcia L.,Institute Municipal dInvestigacio Medica | Prieto R.,Endocrine Surgery Unit | Pena M.J.,Institute Municipal dInvestigacio Medica | And 2 more authors.
British Journal of Surgery | Year: 2010

Background: The bone mineral density (BMD) response to parathyroidectomy is heterogeneous and difficult to predict. Available data come from mixed populations of men and women, of different age and degrees of disease severity, and preoperative BMD loss. Methods: This was a longitudinal, prospective cohort study of 103 postmenopausal women, with. osteopenia or osteoporosis at the femoral neck site, successfully operated on for primary hyperparathyroidism. BMD and metabolic variables were recorded before and 1 year after parathyroidectomy. Results: After surgery, there was a 1-3 percent increase in the median BMD at the femoral neck site (0-615 versus 0-623 g/cm2; P = 0-001). Overall, positive responses were also observed at total hip (0-4 per cent) and lumbar spine (2-3 per cent) sites. Analysing the individual responses, however, only 45 (46 per cent) of 97 patients showed a significant (at least 3-7 per cent) increase in BMD at the femoral neck site compared with the preoperative value and 52 had a decreased (15) or unchanged (37) femoral neck BMD. Patients who gained BMI) were younger, had more severe hyperparathyroidism, and better renal function. Conclusion: Almost half of the postmenopausal women with hyperparathyroidism and low BMD have a significant remineralization response 1 year after parathyroidectomy. Differential mineralization responses of BMD after surgery appear to be related to severity of primary hyperparathyroidism, age and renal function. Copyright © 2010 British Journal of Surgery Society Ltd.


Perez L.M.,Institute Municipal dInvestigacio Medica | Farriols C.,Institute Municipal dInvestigacio Medica | Puente V.,Institute Municipal dInvestigacio Medica | Planas J.,Institute Municipal dInvestigacio Medica | Ruiz I.,Institute Municipal dInvestigacio Medica
Palliative Medicine | Year: 2011

Parkinson's disease (PD) is a degenerative, chronic and irreversible condition. Palliative medicine may play an important role in the care of patients with PD to maintain the quality of life. Scopolamine is a non-competitive antagonist at muscarinic acetylcholine receptors, which was used many years ago in the treatment for PD. To the best of our knowledge, there are no previously reported cases of the use of scopolamine for symptom relief at the end of life in patients with PD. The case reported here shows that treatment with a subcutaneous scopolamine was a useful alternative in a terminal cancer patient with severe tremors unable to take oral PD medication. © 2011 The Author(s).

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