Romero-Gomez M.,Hospital Universitario Of Valme |
Eslam M.,Hospital Universitario Of Valme |
Ruiz A.,NeoCodex |
Maraver M.,Hospital Universitario Of Valme
Liver International | Year: 2011
Hepatitis C virus contact and infection show three different phenotypes: spontaneous viral clearance (SVC), chronic hepatitis C (CHC) and sustained virological response (SVR) following antiviral treatment. Many factors, including genetics, influence the evolution of these three phenotypes. We performed a literature search (PubMed) up to 31 January 2010 without language restriction to identify relevant studies on genes and hepatitis C. Additional studies were sought by reviewing the reference lists of the identified articles. Meta-analysis (using Meta-disk 1.4) was conducted to evaluate the association of single nucleotide polymorphism (SNP) in the IL28B region and SVR. The candidate gene approach showed strong relationships between human leucocyte antigen class II (DQB1 *0301 and DRB1 *1101) and SVC. A cirrhosis risk score involving 7 SNPs has been validated recently. The set of odds ratios of studies demonstrated an association between SNP (rs12987960/rs8099917) in the IL28B and SVR in CHC treated with peginterferon plus ribavirin (OR: 4.6; 95% CI: 2.9-7.3). The overall distribution of protective allele correlated with ethnic differences in SVR (Asians, Europeans, Hispanic and Afro-Americans) together with SVC, but not with fibrosis stage or viral load. These polymorphisms did not influence SVR in very-easy-to-treat patients such as genotype 2/3, rapid virological responders or patients with acute hepatitis C. While the genetic fingerprint for fibrosis progression remains elusive, IL28b polymorphism predicts SVC and SVR. However, nearly half of patients achieving SVR did not show favourable genotype. Further genetic signals are warranted to complete the puzzle of factors influencing hepatitis C. © 2011 John Wiley & Sons A/S.
Campos-Rodriguez F.,Hospital Universitario Of Valme |
Martinez-Garcia M.A.,Polytechnic University of Valencia |
Martinez-Garcia M.A.,CIBER ISCIII |
Reyes-Nunez N.,Hospital Universitario Of Valme |
And 3 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2014
Rationale: It is unknown whether obstructive sleep apnea (OSA) may be a risk factor for incident cardiovascular events in women. Objectives: We sought to investigate whether OSA increases the incidence of a composite of stroke or coronary heart disease (CHD) in women, and the role of continuous positive airway pressure (CPAP) treatment on this association. Methods: This was a prospective, observational study conducted in two Spanish teaching hospitals between 1998 and 2007. Consecutive women referred for suspected OSA and free of previous stroke and CHD were analyzed. Women with an apnea - hypopnea index (AHI) less than 10 comprised the control group, and those with an AHI greater than or equal to 10 were diagnosed with OSA and classi fi ed as CPAP-treated (adherence ≥ 4 h/d) or untreated (adherence < 4 h/d or not prescribed). The follow-up ended in December 2010. Measurements and Main Results: A total of 967 women were studied (median follow-up, 6.8 yr; interquartile range, 5.2-8.2). The untreated OSA group showed a greater incidence rate of the composite outcome than the control group (2.19 vs. 0.54 per 100 person-years; P < 0.0005). Compared with the control group, the fully adjusted hazard ratios for the composite outcome incidence were 2.76 (95% confidence interval [CI], 1.35-5.62) for the untreated OSA group, and 0.91 (95% CI, 0.43-1.95) for the CPAP-treated group.Whenthe type of cardiovascular event was separately assessed, untreated OSA showed a stronger association with incident stroke (adjusted hazard ratio, 6.44; 95% CI, 1.46-28.3) than with CHD (adjusted hazard ratio, 1.77; 95% CI, 0.76-4.09). Conclusions: In women, untreatedOSAis associated with increased incidence of serious cardiovascular outcomes, particularly incident stroke. Adequate CPAP treatment seems to reduce this risk. Copyright © 2014 by the American Thoracic Society.
Nauck M.A.,Diabetes Center |
Del Prato S.,University of Pisa |
Duran-Garcia S.,Hospital Universitario Of Valme |
Rohwedder K.,Astrazeneca |
And 3 more authors.
Diabetes, Obesity and Metabolism | Year: 2014
Aims: To assess the long-term glycaemic durability, safety and tolerability of dapagliflozin versus glipizide as add-on therapies in patients with type 2 diabetes inadequately controlled by metformin alone. Methods: This was a 52-week, randomised, double-blind study of dapagliflozin (n=406) versus glipizide (n=408), uptitrated over 18weeks according to tolerability and glycaemic response to a maximum of 10 and 20mg/day, respectively, as add-on therapies to metformin (≥1500mg/day) with a 156-week double-blind extension period. Data over 104weeks are reported here. Results: In total, 53.1% of patients completed 104weeks of treatment. After the greater initial decrease (0-18weeks) in glycated haemoglobin (HbA1c) with glipizide, the 18-104-week HbA1c coefficient of failure (CoF) was lower with dapagliflozin (0.13%/year) than with glipizide (0.59%/year), resulting in significant dapagliflozin versus glipizide differences of -0.46%/year (95% CI -0.60,-0.33; p=0.0001) for CoF and -0.18%(-2.0mmol/mol) [95% CI -0.33(-3.6),-0.03(-0.3); p=0.021] for 104-week HbA1c. Dapagliflozin produced sustained reductions in weight and systolic blood pressure, whereas glipizide increased weight and systolic blood pressure, giving 104-week dapagliflozin versus glipizide differences of -5.1kg (95% CI: -5.7,-4.4) and -3.9mmHg (95% CI: -6.1,-1.7), respectively. Over 104weeks, the hypoglycaemia rate was 10-fold lower with dapagliflozin than with glipizide (4.2 vs. 45.8%), whereas patient proportions with events suggestive of genital infection and of urinary tract infection (UTI) were greater with dapagliflozin (14.8 and 13.5%, respectively) than with glipizide (2.9 and 9.1%, respectively). Conclusions: Over 2years, compared with glipizide, dapagliflozin demonstrated greater glycaemic durability, sustained reductions in weight and systolic blood pressure and a low hypoglycaemia rate; however, genital infections and UTIs occurred more frequently. © 2014 John Wiley & Sons Ltd.
Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: A randomized, 52-week, double-blind, active-controlled noninferiority trial
Nauck M.A.,Diabetes Center |
Del Prato S.,University of Pisa |
Meier J.J.,Ruhr University Bochum |
Duran-GARCIA S.,Hospital Universitario Of Valme |
And 3 more authors.
Diabetes Care | Year: 2011
OBJECTIVE - Although initially effective, sulfonylureas are associated with poor glycemic durability, weight gain, and hypoglycemia. Dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), reduces hyperglycemia by increasing urinary glucose excretion independent of insulin andmay cause fewer of these adverse effects. We compared the efficacy, safety, and tolerability of dapagliflozin with the sulfonylurea glipizide in patients with type 2 diabetes inadequately controlled with metformin monotherapy. RESEARCH DESIGN AND METHODS - This 52-week, double-blind, multicenter, active-controlled, noninferiority trial randomized patients with type 2 diabetes (baseline mean HbA 1c, 7.7%), who were receiving metforminmonotherapy, to add-on dapagliflozin (n = 406) or glipizide (n = 408) up-titrated over 18 weeks, based on glycemic response and tolerability, to ≤10 or ≤20 mg/day, respectively. RESULTS - The primary end point, adjusted mean HbA 1c reduction with dapagliflozin (-0.52%) compared with glipizide (-0.52%), was statistically noninferior at 52 weeks. Key secondary end points: dapagliflozin produced significant adjusted mean weight loss (-3.2 kg) versus weight gain (1.2 kg; P < 0.0001) with glipizide, significantly increased the proportion of patients achieving ≥5% body weight reduction (33.3%) versus glipizide (2.5%; P < 0.0001), and significantly decreased the proportion experiencing hypoglycemia (3.5%) versus glipizide (40.8%; P < 0.0001). Events suggestive of genital infections and lower urinary tract infections were reported more frequently with dapagliflozin compared with glipizide but responded to standard treatment and rarely led to study discontinuation. CONCLUSIONS - Despite similar 52-week glycemic efficacy, dapagliflozin reduced weight and produced less hypoglycemia than glipizide in type 2 diabetes inadequately controlled with metformin. Long-termstudies are required to further evaluate genital and urinary tract infections with SGLT2 inhibitors. © 2011 by the American Diabetes Association.
Mathiesen E.R.,Copenhagen University |
Hod M.,Tel Aviv University |
Ivanisevic M.,University of Zagreb |
Garcia S.D.,Hospital Universitario Of Valme |
And 4 more authors.
Diabetes Care | Year: 2012
OBJECTIVE - This randomized, controlled noninferiority trial aimed to compare the efficacy and safety of insulin detemir (IDet) versus neutral protamine Hagedorn (NPH) (both with prandial insulin aspart) in pregnant women with type 1 diabetes. RESEARCH DESIGN AND METHODS - Patients were randomized and exposed to IDet or NPH up to 12 months before pregnancy or at 8-12 weeks gestation. The primary analysis aimed to demonstrate noninferiority of IDet to NPH with respect to A1C at 36 gestational weeks (GWs) (margin of 0.4%). The data were analyzed using linear regression, taking several baseline factors and covariates into account. RESULTS - A total of 310 type 1 diabetic women were randomized and exposed to IDet (n = 152) or NPH (n = 158) up to 12 months before pregnancy (48%) or during pregnancy at 8-12 weeks (52%). The estimated A1C at 36 GWs was 6.27% for IDet and 6.33% for NPH in the full analysis set (FAS). IDet was declared noninferior to NPH (FAS, -0.06% [95% CI -0.21 to 0.08]; per protocol, -0.15%[-0.34 to 0.04]). Fasting plasma glucose (FPG) was significantly lower with IDet versus NPH at both 24 GWs (96.8 vs. 113.8 mg/dL, P = 0.012) and 36 GWs (85.7 vs. 97.4 mg/dL, P = 0.017). Major and minor hypoglycemia rates during pregnancy were similar between groups. CONCLUSIONS - Treatment with IDet resulted in lower FPG and noninferior A1C in late pregnancy compared with NPH insulin. Rates of hypoglycemia were comparable. © 2012 by the American Diabetes Association.
Tavares E.,Hospital Universitario Of Valme
American journal of physiology. Endocrinology and metabolism | Year: 2013
Aminoprocalcitonin (N-PCT), a neuroendocrine peptide encoded by the calcitonin-I (CALC-I) gene, suppresses food intake when administered centrally in rats. However, the neural pathways underlying this effect remain unclear. N-PCT and calcitonin receptors (CT-R) have been identified in hypothalamic regions involved in energy homeostasis, including the arcuate nucleus (ARC). Here, we hypothesized an involvement of the hypothalamic ARC in mediating the anorexic effects of central N-PCT based on its content of peptidergic neurons involved in feeding and its expression of N-PCT and CT-R. Fasting strongly reduced expression of the N-PCT precursor gene CALC-I in the ARC, and central immunoneutralization of endogenous N-PCT increased food intake. Intracerebroventricular administration of N-PCT reduced food intake in fed and fasted rats, and its effect was attenuated by a neutralizing anti-N-PCT antibody. Immunohistochemistry for N-PCT showed that it is expressed in astrocytes and neurons in the ARC and is colocalized with anorexigenic proopiomelanocortin (POMC) neurons. Fasting reduced coexpression of N-PCT and POMC, and N-PCT administration activated hypothalamic neurons, including rostral POMC neurons. We also found that N-PCT stimulates POMC mRNA expression in fed and fasted rats, whereas it reduced the expression of orexigenic peptides neuropeptide Y (NPY) and agouti-related peptide (AgRP) only in fasted rats in which those mRNAs are normally elevated. Finally, we showed that the melanocortin-3/4 receptor antagonist SHU 9119 attenuates the intake-suppressive effect of N-PCT. These data demonstrate that hypothalamic N-PCT is involved in control of energy balance and that its anorexigenic effects are mediated through the melanocortin system.
Ortiz de la Tabla Gonzalez R.,Hospital Universitario Of Valme
Revista española de anestesiología y reanimación | Year: 2011
Central neuraxial blocks, which are associated with a low incidence of complications, are safe. When complications do occur, however, the resulting morbidity and mortality is considerable. The reported incidence of complications in all series is under 4 per 10000 patients, but given the absence of formal registries and notification procedures, which have legal implications, the real rate of occurrence of these rare events is uncertain. We searched the literature through PubMed and the Cochrane Plus Library for a 5-year period, using the search terms epidural anesthesia AND safety, spinal anesthesia AND safety, complications AND epidural anesthesia, complications AND spinal anesthesia, neurologic complications AND epidural anesthesia, and neurologic complications AND spinal anesthesia. Neuraxial injury after a central blockade may be the result of anatomical and/or physiological lesions affecting the spinal cord, spinal nerves, nerve roots, or blood supply. The pathophysiology of neuraxial injury may be related to mechanical, ischemic, or neurotoxic damage or any combination. When a complication occurs, factors related to the technique will have interacted with pre-existing patient-related conditions. Various scientific societies have published guidelines for managing the complications of regional anesthesia. Recently published clinical practice guidelines recommend ultrasound imaging as a useful tool in performing a central neuraxial block.
Association of NAFLD with subclinical atherosclerosis and coronary-artery disease: Meta-analysis [Asociación de la enfermedad grasa del hígado no alcohólica con arteriosclerosis subclínica y enfermedad coronaria: Un metaanálisis]
Ampuero J.,Hospital Universitario Of Valme |
Gallego-Duran R.,Hospital Universitario Of Valme |
Romero-Gomez M.,Hospital Universitario Of Valme
Revista Espanola de Enfermedades Digestivas | Year: 2015
Background: Recent studies have associated non-alcoholic fatty liver disease (NAFLD) with increased risk of cardiovascular disease, using tests of subclinical atherosclerosis. Aim: To evaluate the influence of NAFLD on subclinical atherosclerosis and coronary artery disease (CAD). Methods: We reviewed Pubmed and EMBASE. According to inclusion and exclusion criteria, we selected 14 studies and were classified in two groups. Ten studies aimed the presence of subclinical atherosclerosis and four studies the presence of coronary artery disease. To assess subclinical atherosclerosis, we selected studies with pathological carotid intima-media thickness (CIMT) and with presence of carotid plaques. We considered coronary artery disease when patients showed at least 50 % stenosis at one or more major coronary arteries. NAFLD was assessed by ultrasound (US) and liver biopsy. Results: NAFLD showed a higher prevalence of pathological CIMT [35.1 % (351/999) vs. 21.8 % (207/948); p < 0.0001], with OR 2.04 (95 % CI: 1.65-2.51). Similarly, the presence of carotid plaques was higher in NAFLD diagnosed by US [34.2 % (101/295) vs. 12.9 % (51/394); p < 0.0001] [OR 2.82 (95 % CI: 1.87-4.27)] and diagnosed by liver biopsy [64.8 % (70/108) vs. 31.3 % (59/188); p < 0.0001] [OR 4.41 (95 % CI: 2.63- 7.40)]. On the other hand, four studies assessed CAD in patients underwent coronary angiogram. Subjects with NAFLD showed 80.4 % (492/612) of CAD, while it was detected in 60.7 % (356/586) (p < 0.0001) in patients without NAFLD. Therefore, NAFLD was associated with a remarkably higher likelihood of CAD, using random effects model [OR 3.31 (95 % CI: 2.21-4.95)] or fixed effects model [OR 3.13 (95 % CI: 2.36-4.16)]. Conclusions: NAFLD increases the risk of subclinical atherosclerosis and coronary artery disease. The right management of these patients could modify the natural history both liver and cardiovascular disease. © 2015 Arán Ediciones, S. L.
Puig-Asensio M.,Autonomous University of Barcelona |
Peman J.,Polytechnic University of Valencia |
Zaragoza R.,Hospital Universitario Dr Peset |
Garnacho-Montero J.,Hospital Universitario Virgen Del Rocio |
And 3 more authors.
Critical Care Medicine | Year: 2014
OBJECTIVES: To determine the epidemiology of Candida bloodstream infections, variables influencing mortality, and antifungal resistance rates in ICUs in Spain. DESIGN: Prospective, observational, multicenter population-based study. SETTING: Medical and surgical ICUs in 29 hospitals distributed throughout five metropolitan areas of Spain. PATIENTS: Adult patients (≥ 18 yr) with an episode of Candida bloodstream infection during admission to any surveillance area ICU from May 2010 to April 2011. INTERVENTIONS: Candida isolates were sent to a reference laboratory for species identification by DNA sequencing and susceptibility testing using the methods and breakpoint criteria promulgated by the European Committee on Antimicrobial Susceptibility Testing. Prognostic factors associated with early (0-7 d) and late (8-30 d) mortality were analyzed using logistic regression modeling. MEASUREMENTS AND MAIN RESULTS: We detected 773 cases of candidemia, 752 of which were included in the overall cohort. Among these, 168 (22.3%) occurred in adult ICU patients. The rank order of Candida isolates was as follows: Candida albicans (52%), Candida parapsilosis (23.7%), Candida glabrata (12.7%), Candida tropicalis (5.8%), Candida krusei (4%), and others (1.8%). Overall susceptibility to fluconazole was 79.2%. Cumulative mortality at 7 and 30 days after the first episode of candidemia was 16.5% and 47%, respectively. Multivariate analysis showed that early appropriate antifungal treatment and catheter removal (odds ratio, 0.27; 95% CI, 0.08-0.91), Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.11; 95% CI, 1.04-1.19), and abdominal source (odds ratio, 8.15; 95% CI, 1.75-37.93) were independently associated with early mortality. Determinants of late mortality were age (odds ratio, 1.04; 95% CI, 1.01-1.07), intubation (odds ratio, 7.24; 95% CI, 2.24-23.40), renal replacement therapy (odds ratio, 6.12; 95% CI, 2.24-16.73), and primary source (odds ratio, 2.51; 95% CI, 1.06-5.95). CONCLUSIONS: Candidemia in ICU patients is caused by non-albicans species in 48% of cases, C. parapsilosis being the most common among these. Overall mortality remains high and mainly related with host factors. Prompt adequate antifungal treatment and catheter removal could be critical to decrease early mortality. © 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.
Eslam M.,Hospital Universitario Of Valme
Annals of hepatology | Year: 2013
This study assessed the involvement of metabolic factors (anthropometric indices, insulin resistance (IR) and adipocytokines) in the prediction of portal hypertension, esophageal varices and risk of variceal bleeding in cirrhotic patients. Two prospective and retrospective cohorts of cirrhotic patients were selected (n = 357). The first prospective cohort (n = 280) enrolled consecutively in three centers, underwent upper gastrointestinal endoscopy, seeking evidence of esophageal varices. Clinical, anthropometric, liver function tests, ultrasonographic, and metabolic features were recorded at the time of endoscopy, patients were followed-up every 6 months until death, liver transplantation or variceal bleeding. The second retrospective cohort (n = 48 patients) had measurements of the hepatic venous pressure gradient (HVPG). Statistical analyses of the data were with the SPSS package. The presence of esophageal varices was independently associated with lower platelet count, raised HOMA index and adiponectin levels. This relationship extended to subset analysis in patients with Child A cirrhosis. HOMA index and adiponectin levels significantly correlated with HVPG. Beside Child-Pugh class, variceal size and glucagonemia, HOMA index but not adiponectin and leptin plasma levels were associated with higher risk of variceal bleeding. In patients with cirrhosis, HOMA score correlates with HVPG and independently predict clinical outcomes. Three simple markers i.e. platelet count, IR assessed by HOMA-IR and adiponectin significantly predict the presence of esophageal varices in cirrhotic patients.