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Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't; BACKGROUND Multiple sensitization is frequent among pollen-allergic patients. The goal of this study was to determine the diagnostic accuracy of the ImmunoCAP ISAC 112 (ISAC112) microarray in allergy to pollen from several taxa and its clinical utility in a Spanish population. METHODS Specific IgE was determined in 390 pollen-allergic patients using the ISAC112 microarray. Diagnostic accuracy (sensitivity, specificity, predictive values, and area under the ROC curve) was calculated for the diagnosis of allergy to pollen from grass (n=49), cypress (n=75), olive tree (n=33), plane tree (n=63), and pellitory of the wall (n=17) and compared with that of the singleplex ImmunoCAP immunoassay. RESULTS The sensitivity of the ISAC112 microarray ranged from 68.2% for allergy to plane tree pollen to 93.9% for allergy to grass pollen. The specificity was >90%. The AUC for the diagnosis of allergy to plane tree pollen was 0.798, whereas the AUC for the remaining cases was ≥0.876. The accuracy of ISAC112 was higher than that of ImmunoCAP for plane tree pollen and similar for the remaining pollens. The frequency of sensitization to most species-specific allergenic components and profilins varied between the different geographical regions studied. A total of 73% of pollen-allergic patients were sensitized to species-specific components of more than 1 pollen type. CONCLUSIONS The ISAC112 microarray is an accurate tool for the diagnosis of allergy to pollen from grass, cypress, olive tree, plane tree, and pellitory of the wall. The features of the ISAC112 microarray are similar or superior (in the case of plane tree pollen) to those of ImmunoCAP. This microarray is particularly useful for the etiologic diagnosis of pollinosis in patients sensitized to multiple pollen species whose pollination periods overlap. Yes

English Abstract; Journal Article; BACKGROUND The suicide mortality rate in Andalusia is higher than the Spanish average, and it shows a different evolution over time. This study analyzes recent changes of suicide mortality in Andalusia, its geographical distribution and its relation with antidepressant use, altitude and socioeconomic inequality. METHODS An ecological study of the Basic Health Zones in Andalusia has been conducted. Age-standarized suicide rates in 2012 and during 2007-2011 were calculated. The correlation among variables and their association with the geographical differences was assessed with Spearman's coefficient and generalized linear models were also estimated. RESULTS Andalusia registered 7,58 suicides per 100.000 inhabitants per year from 2007 to 2011, with a range of 0,96 to 27,71 in the different areas. Positive correlation has been observed between altitude and suicide rates in 2012 (r=0,29; p

There is an increasing trend in the incidence of cancer worldwide, and it has been accepted that environmental factors account for an important proportion of the global burden. The present paper reports preliminary findings on the influence of the historical exposure to a group of persistent organic pollutants on total cancer risk, at year 9 in the follow-up of a cohort from Southern Spain. A cohort of 368 participants (median age 51 years) was recruited in 2003. Their historical exposure was estimated by analyzing residues of persistent organic pollutants in adipose tissue. Estimation of cancer incidence was based on data from a population-based cancer registry. Statistical analyses were performed using multivariable Cox-regression models. In males, PCB 153 concentrations were positively associated with total cancer risk, with an adjusted hazard ratio (95% confidence interval) of 1.20 (1.01–1.41) for an increment of 100 ng/g lipid. Our preliminary findings suggest a potential relationship between the historical exposure to persistent organic pollutants and the risk of cancer in men. However, these results should be interpreted with caution and require verification during the future follow-up of this cohort., This study was supported in part by research grants from the Spanish Ministry of Health (FIS 02/974, EUS2008-03574), CIBER de Epidemiología; Junta de Andalucía (01/264, P09-CTS-5488 Project of Excellence, PI-0675-2010, and PI-0513-2012), and the Instituto de Salud Carlos III (FIS PI11/0610).

English Abstract; Journal Article; Validation Studies; BACKGROUND Job satisfaction of nurses is a determinant factor in the quality and organizational adaptation of clinical management models in the current socio-economic context. The aim of this study was to construct and validate a questionnaire to measure job satisfaction of nurses in the Clinical Management Units in the Andalusian Public Health System. METHODS Clinimetric and cross-sectional study with a sample of 314 nurses of two university hospitals from Seville. Nurses were surveyed in 2011, from March to June. We used the Font Roja questionnaire adapted to our study variables. We performed analyses of correlations, reliability and construct validity, using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to test the a priori model. RESULTS The end questionnaire consists of 10 items, whose internal consistency was 0.75, with a percentage of variance explaining of 63.67%. CFA confirmed 4 dimensions (work environment, work relationships, motivation, and recognition): significant χ2 (p < .001); χ2/gl = 2.013; GFI= 0.958, RMR = 0.055 y RMSEA = 0.057; AGFI = 0.927, NFI = 0.878, TLI = 0.902, CFI =0.933 e IFI = 0.935; AIC = 132.486 y ECVI = 0.423. CONCLUSION This new questionnaire (G_Clinic) improves clinimetric values of the Font Roja questionnaire, because it reduces the number of items, improves the reliability of the dimensions, increases the value of variance explained, and allows knowing job satisfaction of nurses in clinical managementt. Yes Fundamentos: La satisfacción laboral de los profesionales de enfermería es un factor determinante en la calidad y adaptación organizativa de los modelos de gestión clínica en el actual contexto socioeconómico. El objetivo del estudio fue construir y validar un cuestionario para conocer el nivel de satisfacción laboral de los profesionales enfermeros en las Unidades de Gestión Clínica en el Sistema Sanitario Público Andaluz. Métodos: Estudio clinimétrico y transversal, tomando como muestra a 314 profesionales de enfermería pertenecientes a los Hospitales Universitarios Virgen del Rocío y Virgen Macarena de Sevilla. Las encuestas se realizaron en 2011, entre los meses de marzo a junio. Se utilizó como base el cuestionario Font Roja adaptado a las variables de nuestra investigación. Se realizó el análisis de correlaciones, fiabilidad, validez de constructo mediante Análisis Factorial Exploratorio (AFE) y Análisis Factorial Confirmatorio (AFC) para comprobar el modelo apriorístico. Resultados: Se construyó un cuestionario con 10 ítems, cuya consistencia interna es de 0,75 con un porcentaje explicativo de la varianza del 63,67%. El AFC corroboró 4 dimensiones (clima laboral, relaciones laborales, motivación y reconocimiento): χ2 significativo (p < .001); χ2/gl = 2.013; GFI= 0.958, RMR = 0.055 y RMSEA = 0.057; AGFI = 0.927, NFI = 0.878, TLI = 0.902, CFI = 0.933 e IFI = 0.935; AIC = 132.486 y ECVI = 0.423. Conclusiones: Este nuevo cuestionario (G_Clinic) mejora los valores del cuestionario Font Roja, ya que disminuye el número de ítems, mejora la fiabilidad de cada una de las dimensiones, aumenta el valor de la varianza explicada y posibilita conocer la satisfacción de los profesionales de enfermería en la gestión clínica.

Purpose. To survey the management of patients with neovascular age-related macular degeneration (nvAMD) in Spain.Methods. An observational retrospective multicenter study was conducted. The variables analyzed were sociodemographic characteristics, foveal and macular thickness, visual acuity (VA), type of treatment, number of injections, and the initial administration of a loading dose of an antiangiogenic drug.Results. 208 patients were followed up during 23.4 months in average. During the first and second years, patients received a mean of4.5±1.8and1.6±2.1injections of antiangiogenic drugs, and5.4±2.8and3.6±2.2follow-up visits were performed, respectively. The highest improvement in VA was observed at 3 months of follow-up, followed by a decrease in the response that stabilized above baseline values until the end of the study. Patients who received an initial loading dose presented greater VA gains than those without.Conclusions. Our results suggest the need for a more standardized approach in the management and diagnosis of nvAMD receiving VEGF inhibitors. To achieve the visual outcomes reported in pivotal trials, an early diagnosis, proactive approach (more treating than follow-up visits), and a close monitoring might be the key to successfully manage nvAMD.

Journal Article; Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. BACKGROUND AND OBJECTIVE Patients from a previous study of neuropathic pain (NP) in the Spanish primary care setting still had symptoms despite treatment. Subsequently, patients were treated as prescribed by their physician and followed up for 3 months. Since pregabalin has been shown to be effective in NP, including refractory cases, the objective of this study was to assess the effectiveness of pregabalin therapy in patients with NP refractory to previous treatments. METHODS This was a post hoc analysis of pregabalin-naïve NP patients treated with pregabalin in a 3-month follow-up observational multicenter study to assess symptoms and satisfaction with treatment. Patients were evaluated with the Douleur Neuropathique en 4 questions (DN4), the Brief Pain Inventory (BPI) and the Treatment Satisfaction for Medication Questionnaire (SATMED-Q) overall satisfaction domain. RESULTS 1,670 patients (mean age 58 years, 59 % women), previously untreated or treated with ≥1 drug other than pregabalin, were treated with pregabalin (37 % on monotherapy). At 3 months, pain intensity and its interference with activities decreased by half (p

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Journal Article; INTRODUCTION The Rasch model is increasingly used in the field of rehabilitation because it improves the accuracy of measurements of patient status and their changes after therapy. OBJECTIVE To determine the long-term effectiveness of a holistic neuropsychological rehabilitation program for Spanish outpatients with acquired brain injury (ABI) using Rasch analysis. METHODS Eighteen patients (ten with long evolution - patients who started the program > 6 months after ABI- and eight with short evolution) and their relatives attended the program for 6 months. Patients' and relatives' answers to the European Brain Injury Questionnaire and the Frontal Systems Behavior Scale at 3 time points (pre-intervention. post-intervention and 12 month follow-up) were transformed into linear measures called logits. RESULTS The linear measures revealed significant improvements with large effects at the follow-up assessment on cognitive and executive functioning, social and emotional self-regulation, apathy and mood. At follow-up, the short evolution group achieved greater improvements in mood and cognitive functioning than the long evolution patients. CONCLUSIONS The program showed long-term effectiveness for most of the variables, and it was more effective for mood and cognitive functioning when patients were treated early. Relatives played a key role in the effectiveness of the rehabilitation program. Yes

et al., There is limited information on the role of penicillin-binding proteins (PBPs) in the resistance of Acinetobacter baumannii to β-lactams. This study presents an analysis of the allelic variations of PBP genes in A. baumannii isolates. Twenty-six A. baumannii clinical isolates (susceptible or resistant to carbapenems) from three teaching hospitals in Spain were included. The antimicrobial susceptibility profile, clonal pattern, and genomic species identification were also evaluated. Based on the six complete genomes of A. baumannii, the PBP genes were identified, and primers were designed for each gene. The nucleotide sequences of the genes identified that encode PBPs and the corresponding amino acid sequences were compared with those of ATCC 17978. Seven PBP genes and one monofunctional transglycosylase (MGT) gene were identified in the six genomes, encoding (i) four high-molecular-mass proteins (two of class A, PBP1a [ponA] and PBP1b [mrcB], and two of class B, PBP2 [pbpA or mrdA] and PBP3 [ftsI]), (ii) three low-molecular-mass proteins (two of type 5, PBP5/6 [dacC] and PBP6b [dacD], and one of type 7 (PBP7/8 [pbpG]), and (iii) a monofunctional enzyme (MtgA [mtgA]). Hot spot mutation regions were observed, although most of the allelic changes found translated into silent mutations. The amino acid consensus sequences corresponding to the PBP genes in the genomes and the clinical isolates were highly conserved. The changes found in amino acid sequences were associated with concrete clonal patterns but were not directly related to susceptibility or resistance to β-lactams. An insertion sequence disrupting the gene encoding PBP6b was identified in an endemic carbapenem-resistant clone in one of the participant hospitals., This work was partially supported by the Instituto de Salud Carlos III, Spanish Network for Research in Infectious Diseases (REIPI, RD06/0008), and FIS (PI080209). We are grateful to the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), which gave a PDEE grant to R.C. (protocol 4149/08-4). We acknowledge the funding of MICINN (BFU2009-09200) to J.A.A.

Data on fungemia epidemiology and antifungal susceptibility of isolates from children are scarce, leading frequently to pediatric empirical treatment based on available adult data. The present study was designed to update the epidemiological, mycological, and in vitro susceptibility data on fungal isolates from children with fungemia in Spain. All fungemia episodes were identified prospectively by blood culture over 13 months at 30 hospitals. Tests of susceptibility to amphotericin B, flucytosine, fluconazole, itraconazole, posaconazole, voriconazole, anidulafungin, caspofungin, and micafungin were performed at participant institutions by a microdilution colorimetric method. New species-specific clinical breakpoints for fluconazole, voriconazole, and echinocandins were also applied. A total of 203 episodes of fungemia in 200 children were identified. A higher proportion of fungal isolates was from general wards than intensive care units (ICU). Candida parapsilosis (46.8%), Candida albicans (36.5%), Candida tropicalis (5.9%), Candida glabrata (3.9%), and Candida guilliermondii (2.5%) were the leading species. C. parapsilosis was the predominant species except in neonates. C. albicans was the most frequent in neonatal ICU settings (51.9%). Intravascular catheter (79.3%), surgery (35%), prematurity (30%), and neutropenia (11%) were the most frequent predisposing factors. Most Candida isolates (95.1%) were susceptible to all antifungals. When the new species-specific clinical breakpoints were applied, all C. parapsilosis isolates were susceptible to echinocandins except one, which was micafungin resistant. This is the largest published series of fungemia episodes in the pediatric setting. C. parapsilosis is the most prevalent species in Spain, followed by C. albicans and C. tropicalis . Resistance to azole and echinocandin agents is extremely rare among Candida species. The fluconazole resistance rate in Spain has decreased in the last 10 years.

Background: A growing body of research suggests that prenatal exposure to air pollution may be harmful to fetal development. We assessed the association between exposure to air pollution during pregnancy and anthropometric measures at birth in four areas within the Spanish Children’s Health and Environment (INMA) mother and child cohort study. Methods: Exposure to ambient nitrogen dioxide (NO2) and benzene was estimated for the residence of each woman (n = 2,337) for each trimester and for the entire pregnancy. Outcomes included birth weight, length, and head circumference. The association between residential outdoor air pollution exposure and birth outcomes was assessed with linear regression models controlled for potential confounders. We also performed sensitivity analyses for the subset of women who spent more time at home during pregnancy. Finally, we performed a combined analysis with meta-analysis techniques. Results: In the combined analysis, an increase of 10 µg/m3 in NO2 exposure during pregnancy was associated with a decrease in birth length of –0.9 mm [95% confidence interval (CI), –1.8 to –0.1 mm]. For the subset of women who spent ≥ 15 hr/day at home, the association was stronger (–0.16 mm; 95% CI, –0.27 to –0.04). For this same subset of women, a reduction of 22 g in birth weight was associated with each 10-µg/m3 increase in NO2 exposure in the second trimester (95% CI, –45.3 to 1.9). We observed no significant relationship between benzene levels and birth outcomes. Conclusions: NO2 exposure was associated with reductions in both length and weight at birth. This association was clearer for the subset of women who spent more time at home. This study was funded by grants from the Instituto de Salud Carlos III (Red INMA G03/176 and CB06/02/0041), the Spanish Ministry of Health (FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 04/1436, 05/1079, 05/1052, 06/1213, 07/0314, 08/1151, 09/02311, 09/02647), Conselleria de Sanitat Generalitat Valenciana, Generalitat de Catalunya-CIRIT 1999SGR 00241, and the Fundación Roger Torné

BACKGROUND Increasing trend and geographical variations in the use of caesarean section suggest the influence of non-clinical factors. The objective was to describe the use of caesarean section in the Andalusian region in Spain by exploring the role of social, clinical, and health services variables. METHODS A cross-sectional study was carried out using vital statistics. It involves all births occurred in Andalusia during the period of 2007-2009. The dependent variable was the use of caesarean section and the set of covariates were classified into three groups: those with a clinical meaning, those related to the health services organization, and those with a social significance. Multivariate logistic regressions were used. RESULTS In the data set of 293,558 births, the prevalence of caesarean delivery was 24.8%. The multivariate analysis highlights the labour complications as the clinical variable with the highest odds ratio (OR=19.36). Regarding the health services variables, the odds of experiencing a caesarean delivery were 55% higher on weekdays than on weekends. Cádiz was the province with the highest OR for caesarean section (comparison between Cádiz and Almería: OR=1,21) where the ratio between births in public and private hospitals was 3.7. The frequency of caesarean section was 34% higher in women with third level education than those with no education. CONCLUSIONS Labour complication is the most influential variable for caesarean section. Caesarean birth rate is above the accepted standards for all social classes and increases with educational level. Inter-provincial differences reflect different patterns with regard to the use of private medicine. Yes Fundamento: La tendencia creciente y variabilidad geográ­fica en el uso de la cesárea sugiere la existencia de factores explicativos no clínicos. El objetivo del estudio es analizar el uso de las cesáreas en Andalucía, explorando el papel de varia­bles sociales, clínicas y de los servicios sanitarios. Métodos: Estudio transversal de todos los nacimientos de Andalucía (2007-2009) utilizando como fuente de información el Movimiento Natural de la Población. La variable dependien­te fue la frecuencia de cesáreas y las explicativas se clasificaron en tres grupos: con significado clínico, relacionadas con el fun­cionamiento de los servicios sanitarios, y con significado social. Se realizó una regresión logística multivariante. Resultados: El 24,8% de los 293.558 nacimientos fue por cesárea. En el análisis multivariante se observó que la variable clínica con la mayor odds ratio (OR) fue la existencia de com­plicaciones (OR=19,36). En cuanto a las variables relacionadas con los servicios sanitarios hubo un 55% más cesáreas de lunes a viernes que en fines de semana y la provincia con mayor uso de cesárea fue Cádiz (OR de 1,21 frente a Almería) con una razón de partos en centros públicos frente a privados de 3,7. La frecuencia de cesáreas fue un 34% superior en las mujeres con estudios de tercer grado que en las que no tenían estudios. Conclusiones: La variable con mayor influencia en la prác­tica de cesárea fue la existencia de complicaciones. La tasa de cesárea estuvo por encima de los estándares aceptados en todas las clases sociales, con mayor incidencia a mayor nivel educati­vo. Las diferencias interprovinciales reflejan distintos patrones de uso de la medicina privada

Background Controversy exists concerning the influence of gender in the prognosis of patients with heart failure and no evidence is available from specific heart failure clinics. Hypothesis Women with ambulatory heart failure are managed differently than men, although their prognosis might be better than men. Methods and Results We analyzed the clinical characteristics, complementary test results, treatment, and prognosis in 4720 patients with chronic heart failure seen in 62 specialized clinics forming part of a multicenter registry during a mean follow-up of 40 months. The mean age was 65 ± 12 years and 71% were men. The men were younger than the women and more often had a history of hyperlipidemia and ischemic heart disease. The men had a more advanced heart failure New York Heart Association (NYHA) functional class (III-IV) than the women and a greater frequency of systolic ventricular dysfunction. The men more often received treatment with β-blockers, vasodilators, and antiplatelet aggregators as well as higher mean doses as compared with the women. The overall survival after the follow-up was similar for both genders, although the women had lower rates of survival free of admission for heart failure. Conclusions Despite the mortality of women and men with heart failure being similar, the rate of readmission for heart failure is greater in women in specialized heart failure clinics. These results may be associated with the pharmacological treatment differences observed. Copyright © 2010 Wiley Periodicals, Inc.

This is a copy of an article published in the AIDS Research and Human Retroviruses © 2012 [copyright Mary Ann Liebert, Inc.]; AIDS Research and Human Retroviruses is available online at: http://online.liebertpub.com. Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't; End-stage renal diseases (ESRD) are becoming more frequent in HIV-infected patients. In Europe there is little information about HIV-infected patients on dialysis. A cross-sectional multicenter survey in 328 Spanish dialysis units was conducted in 2006. Information from 14,876 patients in dialysis was obtained (81.6% of the Spanish dialysis population). Eighty-one were HIV infected (0.54%; 95% CI, 0.43-0.67), 60 were on hemodialysis, and 21 were on peritoneal dialysis. The mean (range) age was 45 (28-73) years. Seventy-two percent were men and 33% were former drug users. The mean (range) time of HIV infection was 11 (1-27) years and time on dialysis was 4.6 (0.4-25) years. ESRD was due to glomerulonephritis (36%) and diabetes (15%). HIV-associated nephropathy was not reported. Eighty-five percent were on HAART, 76.5% had a CD4 T cell count above 200 cells, and 73% had undetectable viral load. Thirty-nine percent of patients met criteria for inclusion on the renal transplant (RT) waiting list but only 12% were included. Sixty-one percent had HCV coinfection. HCV-coinfected patients had a longer history of HIV, more previous AIDS events, parenteral transmission as the most common risk factor for acquiring HIV infection, and less access to the RT waiting list (p < 0.05). The prevalence of HIV infection in Spanish dialysis units in 2006 was 0.54% HCV coinfection was very frequent (61%) and the percentage of patients included on the Spanish RT waiting list was low (12%). Yes

This is a copy of an article published in the AIDS Research and Human Retroviruses © [2012] [copyright Mary Ann Liebert, Inc.]; Research and Human Retroviruses is available online at: http://online.liebertpub.com. Journal Article; Our objective was to analyze the prevalence of peripheral arterial disease (PAD) in HIV patients at risk and to compare them with the general population. All HIV patients older than 50 years who attended our unit from October 2005-July 2006 and all persons attending for an annual medical checkup at an employees' insurance association during the same period were invited to participate in the study. Of the latter (n = 407), a person of the same sex and age (+/-5 years) was included for each HIV patient. PAD was assessed by the ankle-brachial index (ABI) in all subjects, and all completed the Edinburgh questionnaire. Ninety-nine HIV patients and 99 persons from the general population of the same age and sex were included in the study. The HIV patients had a greater prevalence of dyslipidemia, diabetes, and PAD, which was symptomatic in five of them and in one subject from the general population. Patients with HIV infection older than 50 had a high prevalence of PAD, and as it was asymptomatic in half the cases, an ABI may be performed in this population to actively look for PAD. Control of cardiovascular risk factors and the use of such drugs as platelet antiaggregation agents should therefore be optimized in this population. Yes

The research leading to these results was funded by the Spanish Ministry of Health (FIS-PI11/00610, FIS-PI041436, FIS-PI081151, FIS-PI042018, and FIS-PI09/02311), the European Union (EU) (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), the Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647, 11/01007, 11/02591, CP11/00178, FIS-PI06/0867, and FIS-PS09/00090), the Conselleria de Sanitat Generalitat Valenciana, the Generalitat de Catalunya-CIRIT (1999SGR 00241), the Obre Social Cajastur, the Universidad de Oviedo, the Department of Health of the Basque Government (2005111093 and 2009111069), and the Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001). The ENVIRONAGE cohort is supported by the EU Program “Ideas” (ERC-2012-StG 310898) and by the Flemish Fund for Scientific Research (FWO 1516112N and G073315N)., Clemente, D.B.P., Casas, M., Vilahur, N., Begiristain, H., Bustamante, M., Carsin, A., Fernández, M.F., Fierens, F., Gyselaers, W., Iñiguez, C., Janssen, B.G., Lefebvre, W., Llop, S., Olea, N., Pedersen, M., Pieters, N., Marina, L.S., Souto, A., Tardón, A., Vanpoucke, C., Vrijheid, M., Sunyer, J., Nawrot, T.S.

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.There is a strong association between genetic polymorphisms and the acenocoumarol dosage requirements. Genotyping the polymorphisms involved in the pharmacokinetics and pharmacodynamics of acenocoumarol before starting anticoagulant therapy would result in a better quality of life and a more efficient use of healthcare resources. The objective of this study is to develop a new algorithm that includes clinical and genetic variables to predict the most appropriate acenocoumarol dosage for stable anticoagulation in a wide range of patients. We recruited 685 patients from 2 Spanish hospitals and 1 primary healthcare center. We randomly chose 80% of the patients (n = 556), considering an equitable distribution of genotypes to form the generation cohort. The remaining 20% (n = 129) formed the validation cohort. Multiple linear regression was used to generate the algorithm using the acenocoumarol stable dosage as the dependent variable and the clinical and genotypic variables as the independent variables. The variables included in the algorithm were age, weight, amiodarone use, enzyme inducer status, international normalized ratio target range and the presence of CYP2C9∗2 (rs1799853), CYP2C9∗3 (rs1057910), VKORC1 (rs9923231) and CYP4F2 (rs2108622). The coefficient of determination (R2) explained by the algorithm was 52.8% in the generation cohort and 64% in the validation cohort. The following R2 values were evaluated by pathology: atrial fibrillation, 57.4%; valve replacement, 56.3%; and venous thromboembolic disease, 51.5%. When the patients were classified into 3 dosage groups according to the stable dosage (21 mg/week), the percentage of correctly classified patients was higher in the intermediate group, whereas differences between pharmacogenetic and clinical algorithms increased in the extreme dosage groups. Our algorithm could improve acenocoumarol dosage selection for patients who will begin treatment with this drug, especially in extreme-dosage patients. The predictability of the pharmacogenetic algorithm did not vary significantly between diseases., This study was funded by a grant from the Spanish Ministry of Health and Social Policy (Instituto de Salud Carlos III, PI07/0710) and the Andalusian Regional Ministry of Health (Progress and Health Foundation, PI-0717-2013)

Journal Article; BACKGROUND Around 27,000 new cases of prostate cancer are diagnosed every year in Spain and 5400 die from this disease. Radiotherapy (RT), alone or combined, has proven to be effective as initial treatment in patients with localized disease. Our objective was to evaluate the use of external beam RT (EBRT) in our region, comparing the indication rate and irradiation rate and examining variability in its application among hospitals. METHODS We conducted a review of RT guidelines and indication studies for prostate cancer (% expected irradiation). Data were gathered from all twelve public healthcare centers in Andalusia (Spain) on RT-treated prostate cancer patients during 2013 (% actual irradiation) and from nine of the centers on RT discharge reports. Information was classified according to type of hospital, tumor risk category and RT treatment (technique, dosage, volume, toxicity). RESULTS The estimated RT rate was 67 % (1289/1917), 43 % were aged > 70 years, 44.7 % had ECOG performance status of 0); 44.7 % had high-risk tumors; 57 % underwent RT associated with hormone therapy; 70 % of patients receiving RT were treated with 3D planning (30 % IGRT); and doses were 70-76 Gy in 70 % of cases and >76 Gy in 10.7 %. Acute gastrointestinal and genitourinary toxicities were

Background Preventable mortality is a good indicator of possible problems to be investigated in the primary prevention chain, making it also a useful tool with which to evaluate health policies particularly public health policies. This study describes inequalities in preventable avoidable mortality in relation to socioeconomic status in small urban areas of thirty three Spanish cities, and analyses their evolution over the course of the periods 1996–2001 and 2002–2007. Methods We analysed census tracts and all deaths occurring in the population residing in these cities from 1996 to 2007 were taken into account. The causes included in the study were lung cancer, cirrhosis, AIDS/HIV, motor vehicle traffic accidents injuries, suicide and homicide. The census tracts were classified into three groups, according their socioeconomic level. To analyse inequalities in mortality risks between the highest and lowest socioeconomic levels and over different periods, for each city and separating by sex, Poisson regression were used. Results Preventable avoidable mortality made a significant contribution to general mortality (around 7.5%, higher among men), having decreased over time in men (12.7 in 1996–2001 and 10.9 in 2002–2007), though not so clearly among women (3.3% in 1996–2001 and 2.9% in 2002–2007). It has been observed in men that the risks of death are higher in areas of greater deprivation, and that these excesses have not modified over time. The result in women is different and differences in mortality risks by socioeconomic level could not be established in many cities. Conclusions Preventable mortality decreased between the 1996–2001 and 2002–2007 periods, more markedly in men than in women. There were socioeconomic inequalities in mortality in most cities analysed, associating a higher risk of death with higher levels of deprivation. Inequalities have remained over the two periods analysed. This study makes it possible to identify those areas where excess preventable mortality was associated with more deprived zones. It is in these deprived zones where actions to reduce and monitor health inequalities should be put into place. Primary healthcare may play an important role in this process This work was partly supported by the FIS-FEDER projects PI080330, PI081713, PI081978, PI0463/2010, PI081017, PI081785, PI081058, PI080142, and the FUNDACIÓN CAJAMURCIA project FFIS/CM10/27

A carbapenem-resistant Acinetobacter baumannii clinical isolate belonging to European clone II and sequence type 2 was recovered from a patient in the Son Espases hospital in Mallorca, Spain. Genetic analysis showed the presence of the bla OXA-23 gene in association with the widely disseminated transposon Tn 2006 . This is the first reported identification of A. baumannii carrying bla OXA-23 in Spain.

Cysteamine has improved survival and prognosis in cystinosis. Increasing numbers of patients reach adulthood and face new challenges such as compliance that wanes over time. The aim of this study was to evaluate adherence to cysteamine treatment in a group of cystinotic patients in Spain in an attempt to identify potential therapy pitfalls and improve the overall care of affected individuals. Despite the impact of cysteamine on prognosis, there is a paucity of data regarding adherence. Thirty-four cystinotic patients (21 male) 38% a parts per thousand yen18 years were enrolled in a voluntary, anonymous survey. Replies were obtained from patients (15/34), mothers (11/34), fathers (4/34) and both parents (4/34). Patient age (median and interquartile range) at diagnosis was 1 year (0.57-1), and patient age at CystagonA (R) initiation was also 1 year (0.8-1.8). Sixteen (47%) were kidney transplant (KTx) recipients; six were retransplanted. Age at first KTx 10 years (8.7-13.7). Patient understanding of multiorgan involvement in cystinosis: 4.1 organs reported; eye 97% and kidney 91%. Cysteamine was given by mother (100%) and father (83%) in < 11 year olds, or self-administered (94%) in a parts per thousand yen11 year olds. Four daily doses in 89% versus 56% in < 11 year olds or a parts per thousand yen11 year olds, with fixed schedule in 94% versus 50% in < 11 or a parts per thousand yen11 year olds and progressive loss of reminders over time. Furthermore, 44% complained of unpleasant smell. Motivation for treatment compliance was 100% versus 40% in < 11 versus a parts per thousand yen11 year olds, respectively. Disease impact in patients < 18 years is as follows: school (29%), social (14%), 'feeling different' (10%); in patients a parts per thousand yen18 years: 'feeling different' (62%), professional (39%) and job absenteeism (31%). Referring physician: paediatric nephrologist (94%) and nephrologist (63%) in < 11 versus a parts per thousand yen11 year olds. Ophthalmological follow-up: 83% versus 38% in < 11 versus a parts per thousand yen11 year olds. Patient opinion of physician expertise: paediatric nephrologist (94%) and nephrologist (44%). New treatment options (65%) and better information (42%) were demanded to improve adherence. Treatment with Cystagon is effective in young patients. However, adherence diminishes over time in adolescents and adults despite disease impact. Strategies such as better information on the disease, patient self-care promotion and facilitated transition to adult healthcare services are required to improve compliance and the clinical management of cystinosis.

Background: Based on the mechanism of action, combining somatostatin analogues (SSAs) with mTOR inhibitors or antiangiogenic agents may provide synergistic effects for the treatment of patients with neuroendocrine tumours (NETs). Herein, we investigate the use of these treatment combinations in clinical practice. Methods: This retrospective cross-sectional analysis of patients with NETs treated with the SSA lanreotide and targeted therapies at 35 Spanish hospitals evaluated the efficacy and safety of lanreotide treatment combinations in clinical practice. The data of 159 treatment combinations with lanreotide in 133 patients was retrospectively collected. Results: Of the 133 patients, with a median age of 59.4 (16-83) years, 70 (52.6 %) patients were male, 64 (48.1 %) had pancreatic NET, 23 (17.3 %) had ECOG PS >= 2, 41 (30.8 %) had functioning tumours, 63 (47.7 %) underwent surgery of the primary tumour, 45 (33.8 %) had received prior chemotherapy, and 115 (86.5 %) had received prior SSAs. 115 patients received 1 lanreotide treatment combination and 18 patients received between 2 and 5 combinations. Lanreotide was mainly administered in combination with everolimus (73 combinations) or sunitinib (61 combinations). The probability of being progression-free was 78.5 % (6 months), 68.6 % (12 months) and 57.0 % (18 months) for patients who only received everolimus plus lanreotide (n = 57) and 89.3 % (6 months), 73.0 % (12 months), and 67.4 % (18 months) for patients who only received sunitinib and lanreotide (n = 50). In patients who only received everolimus plus lanreotide the median time-to-progression from the initiation of lanreotide combination treatment was 25.8 months (95 % CI, 11.3, 40.3) and it had not yet been reached among the subgroup of patients only receiving sunitinib plus lanreotide. The safety profile of the combination treatment was comparable to that of the targeted agent alone. Conclusions: The combination of lanreotide and targeted therapies, mainly everolimus and sunitinib, is widely used in clinical practice without unexpected toxicities and suggests efficacy that should be explored in randomized prospective clinical trials., We thank the participating investigators: Veronica Calderero, Hospital de Barbastro (Huesca); Juana Cano, Hospital General de Ciudad Real; Nieves Diaz, Hospital Universitario (San Juan - Alicante); Emma Dotor, Hospital Parc Tauli (Sabadell) Barcelona; Maria Pilar Escudero, Hospital Clinico Universitario Lozano Blesa (Zaragoza); Jose Luis Firvida, Complexo Hospitalario Universitario de Ourense; Maria Jose Gomez, Hospital Puerta del Mar (Cadiz); Encarnacion Jimenez, Hospital de Jerez (Cadiz); Luis Leon, Hospital Clinico Universitario (Santiago de Compostela); Natalia Lupion, Hospital de Merida (Badajoz); David Marrupe, Hospital de Mostoles (Madrid); Miguel Navarro, Hospital Clinico Universitario (Salamanca); Miguel Ruiz Lopez de Tejada, Hospital Punta de Europa (Algeciras - Cadiz); Raquel Serrano, Hospital Reina Sofia (Cordoba); Diego Soto, Hospital Clinico Universitario (Valladolid); Alexandre Teule, Institut Catala d'Oncologia, Hospital Duran i Reynals (Barcelona); Francisca Vazquez, Hospital Clinico Universitario (Santiago de Compostela). We thank Ignasi Gich Saladich who provided support for the statistical analyses at the behest of the coordinating investigators and Aurora O'Brate who provided medical writing services subsequent to the initial draft of the manuscript, including requesting additional statistical analyses, collation of all author comments, formatting to adapt to publishing requirements, and help with submission. External commercial funding was not received for the retrospective analysis, but Ipsen Pharma, Spain provided funding for the medical writing services.

BACKGROUND: The occurence of the metabolic syndrome (MS) between the renal receptors is one of the major complications after transplantation and is associated with an increased risk of graft failure and high rates of obesity and diabetes new appearance. AIMS: This study aims to investigate the prevalence and risk factors associated with the development of the MS and to evaluate the association between the same with the allograft dysfunction. METHODS: The samples consisted of 138 renal transplant patients, 83 men and 55 women, kidney transplant, which was attended by over five years for the transplant consultation. Were analyzed as potential risk factors for MS: age, sex, body mass index (BMI), weight, hypertension, diabetes, LDL, HDL, triglycerides in serum and immunosuppressive therapy (cyclosporine, tacrolimus, mycophenolate mofetil), was also assessed the prevalence of acute rejection episodes and renal function. RESULTS: The prevalence of MS was 39.85 %. As statistically significant risk factors were obtained the BMI, overweight, HDL cholesterol levels, triglycerides and LDL as well as hypertension and diabetes. There were high rates of acute rejection and differences in story to the glomerular filtration rate. CONCLUSIONS: There is a high prevalence of the MS that severely compromised renal function and graft survival in renal transplant patients, it is very important the control and strict monitoring of all risk factors identified. Yes Introducción: La aparición del síndrome metabólico (SM) entre los receptores renales es una de la mayores complicaciones postrasplante y se asocia con un mayor riesgo de fracaso del injerto y altas tasas de obesidad y diabetes de nueva aparición. Objetivos: Este estudio tiene como objetivo investigar la prevalencia y factores de riesgo asociados al desarrollo del SM y evaluar la asociación del mismo con la disfuncióndel injerto. Métodos: La muestras estuvo formada por 138 pacientes trasplantados renales, 83 hombres y 55 mujeres, trasplantados renales, que asistieron durante cinco años a la consulta postrasplante. Se analizaron como posibles factores de riesgo para DMPT: edad, sexo, índice de masa corporal (IMC), peso, hipertensión, diabetes, LDL, HDL, triglicéridos en suero y terapia inmunosupresora (Ciclosporina, tacrolimus, micofenolato mofetil), también se evaluó la prevalencia de episodios de rechazo agudo y función renal. Resultados: La prevalencia de SM fue del 39,85%. Como factores de riesgo estadísticamente significativos se obtuvieron el IMC, sobrepeso, niveles colesterol HDL, triglicéridos y LDL así como la hipertensión y la diabetes. Se obtuvieron altas tasas de rechazo agudo y diferencias en cuento a la tasa de filtración glomerular. Conclusiones: Existe una alta prevalencia del SM que compromete gravemente la funcion renal y la supervivencia del injerto en pacientes trasplantados renales, Es importantisimo el control y seguimiento estricto de todos los factores de riesgo identificados.

López-Mejías, Raquel et al., [Introduction] A study was conducted to determine whether the human leukocyte antigen (HLA) B alleles are implicated in the susceptibility to Henoch-Schönlein purpura (HSP) in the largest series of Caucasian HSP patients ever assessed for genetic studies., [Methods] The study population was composed of 349 Spanish patients diagnosed with HSP fulfilling the American College of Rheumatology and the Michel et al. classification criteria, and 335 sex and ethnically matched controls. HLA-B phenotypes were determined by sequencing-based typing (SBT) and analyzed by chi-square or Fisher exact test., [Results] A statistically significant increase of HLA-B*41:02 allele in HSP patients when compared with controls was found (8.3% versus 1.5% respectively; P = 0.0001; OR (odds ratio) =5.76 [2.15-19.3]). These results remained statistically significant after adjusting for Bonferroni correction (P = 0.0028). An internal validation also confirmed the susceptibility effect on HSP associated with HLA-B*41:02 (OR = 5.70 [1.98-16.44]). Since a former study described an association between HLA-DRB1*01:03 and HSP susceptibility, we also evaluated the implication of HLA-B*41:02 independently of HLA-DRB1*01:03. Interestingly, the association remained statistically significant (P = 0.0004, OR = 4.97 [1.8-16.9]). No HLA-B association with specific HSP clinical features was found., [Conclusions] Our study indicates that HLA-B*41:02 is associated with the susceptibility to HSP in Spanish patients irrespective of HLA-DRB1 status., This study was supported by a grant from ‘Fondo de Investigaciones Sanitarias’ PI12/00193 (Spain). RLM is a recipient of a Sara Borrell postdoctoral fellowship from the Instituto de Salud Carlos III at the Spanish Ministry of Health (Spain) (CD12/00425). FG and BU are supported by funds from the RETICS Program (RIER) (RD12/0009/0013).

Objetive: identify whether there is an increased risk of adverse perinatal outcomes, like prematurity or decreased weight in newborns, associated with caffeine consumption during the first half of pregnancy in pregnant women of our population. METHODS: transversal study carried out in 1 175 patients from Virgen de las Nieves University Hospital of Granada (Spain). Information about caffeine consumption during first half of gestation and perinatal outcomes was obtained by personal interview, medical records and telephone call after delivery. The average caffeine intake was calculated from meals and drinks included in a validated questionnaire. RESULTS: there was no difference in caffeine consumption in pregnant women with birth weight ≥2 500 g and Yes Objetivo: identificar si existe un aumento del riesgo en resultados perinatales adversos de prematuridad y disminucion del peso de los recien nacidos asociados al consumo de cafeina durante la primera mitad del embarazo en gestantes de nuestra poblacion. Métodos: estudio transversal llevado a cabo en 1.175 gestantes del Hospital Universitario Virgen de las Nieves de Granada (España). La información sobre el consumo de cafeína durante la primera mitad del embarazo y los resultados perinatales estudiados se obtuvieron mediante entrevista personal, consulta de la historia clínica y llamada telefónica tras el parto. La ingesta media de cafeína se calculo a partir de las comidas y bebidas incluidas en un cuestionario validado. Resultados: no hubo diferencias en el consumo de cafeína en gestantes con recién nacidos de peso ≥2.500 g y.

Objective: To assess Spanish and Portuguese patients' and physicians' preferences regarding type 2 diabetes mellitus (T2DM) treatments and the monthly willingness to pay (WTP) to gain benefits or avoid side effects. Methods: An observational, multicenter, exploratory study focused on routine clinical practice in Spain and Portugal. Physicians were recruited from multiple hospitals and outpatient clinics, while patients were recruited from eleven centers operating in the public health care system in different autonomous communities in Spain and Portugal. Preferences were measured via a discrete choice experiment by rating multiple T2DM medication attributes. Data were analyzed using the conditional logit model. Results: Three-hundred and thirty (n=330) patients (49.7% female; mean age 62.4 [SD: 10.3] years, mean T2DM duration 13.9 [8.2] years, mean body mass index 32.5 [6.8] kg/m(2), 41.8% received oral + injected medication, 40.3% received oral, and 17.6% injected treatments) and 221 physicians from Spain and Portugal (62% female; mean age 41.9 [SD: 10.5] years, 33.5% endocrinologists, 66.5% primary-care doctors) participated. Patients valued avoiding a gain in bodyweight of 3 kg/6 months (WTP: (sic)68.14 [95% confidence interval: 54.55-85.08]) the most, followed by avoiding one hypoglycemic event/month (WTP: (sic)54.80 [23.29-82.26]). Physicians valued avoiding one hypoglycemia/week (WTP: (sic)287.18 [95% confidence interval: 160.31-1,387.21]) the most, followed by avoiding a 3 kg/6 months gain in bodyweight and decreasing cardiovascular risk (WTP: (sic)166.87 [88.63-843.09] and (sic)154.30 [98.13-434.19], respectively). Physicians and patients were willing to pay (sic)125.92 (73.30-622.75) and (sic)24.28 (18.41-30.31), respectively, to avoid a 1% increase in glycated hemoglobin, and (sic)143.30 (73.39-543.62) and (sic)42.74 (23.89-61.77) to avoid nausea. Conclusion: Both patients and physicians in Spain and Portugal are willing to pay for the health benefits associated with improved diabetes treatment, the most important being to avoid hypoglycemia and gaining weight. Decreased cardiovascular risk and weight reduction became the third most valued attributes for physicians and patients, respectively.

Journal Article; Lactococcus garvieae is a Gram-positive, catalase negative coccus arranged in pairs or short chains, well-known as a fish pathogen. We report a case of Infective Endocarditis (IE) by L. garvieae in a native valve from a 68-year-old male with unknown history of contact with raw fish and an extensive history of heart disease. This case highlights the reliability of MALDI-TOF MS compared to conventional methods in the identification of rare microorganisms like this. Yes

Journal Article; Observational Study; Research Support, Non-U.S. Gov't; BACKGROUND To determine generic utilities for Spanish chronic obstructive pulmonary disease (COPD) patients stratified by different classifications: GOLD 2007, GOLD 2013, GesEPOC 2012 and BODEx index. METHODS Multicentre, observational, cross-sectional study. Patients were aged ≥40 years, with spirometrically confirmed COPD. Utility values were derived from EQ-5D-3 L. Means, standard deviations (SD), medians and interquartile ranges (IQR) were computed based on the different classifications. Differences in median utilities between groups were assessed by non-parametric tests. RESULTS 346 patients were included, of which 85.5% were male with a mean age of 67.9 (SD = 9.7) years and a mean duration of COPD of 7.6 (SD = 5.8) years; 80.3% were ex-smokers and the mean smoking history was 54.2 (SD = 33.2) pack-years. Median utilities (IQR) by GOLD 2007 were 0.87 (0.22) for moderate; 0.80 (0.26) for severe and 0.67 (0.42) for very-severe patients (p

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)., [Background]: Fragile X syndrome (FXS) is an inherited neurodevelopmental condition characterised by behavioural, learning disabilities, phisical and neurological symptoms. In addition, an important degree of comorbidity with autism is also present. Considered a rare disorder affecting both genders, it first becomes apparent during childhood with displays of language delay and behavioural symptoms.Main aim: To show whether the combination of 10 mg/kg/day of ascorbic acid (vitamin C) and 10 mg/kg/day of α-tocopherol (vitamin E) reduces FXS symptoms among male patients ages 6 to 18 years compared to placebo treatment, as measured on the standardized rating scales at baseline, and after 12 and 24 weeks of treatment. Secondary aims: To assess the safety of the treatment. To describe behavioural and cognitive changes revealed by the Developmental Behaviour Checklist Short Form (DBC-P24) and the Wechsler Intelligence Scale for Children-Revised. To describe metabolic changes revealed by blood analysis. To measure treatment impact at home and in an academic environment. [Methods/Design]: A phase II randomized, double-blind pilot clinical trial. Scope: male children and adolescents diagnosed with FXS, in accordance with a standardized molecular biology test, who met all the inclusion criteria and none of the exclusion criteria. Instrumentation: clinical data, blood analysis, Wechsler Intelligence Scale for Children-Revised, Conners parent and teacher rating scale scores and the DBC-P24 results will be obtained at the baseline (t0). Follow up examinations will take place at 12 weeks (t1) and 24 weeks (t2) of treatment. [Discussion]: A limited number of clinical trials have been carried out on children with FXS, but more are necessary as current treatment possibilities are insufficient and often provoke side effects. In the present study, we sought to overcome possible methodological problems by conducting a phase II pilot study in order to calculate the relevant statistical parameters and determine the safety of the proposed treatment. The results will provide evidence to improve hyperactivity control and reduce behavioural and learning problems using ascorbic acid (vitamin C) and α-tocopherol (vitamin E). The study protocol was approved by the Regional Government Committee for Clinical Trials in Andalusia and the Spanish agency for drugs and health products. [Trial registration]: ClinicalTrials.gov Identifier: NCT01329770 (29 March 2011)., The trial protocol is approved and funded by the Spanish Ministry of Health, Research Funds from FEDER-EU (TRA152, EC10-191 and EC11-434), the Health Department of the Andalusian Regional Government (PI09-0507), the Economic Innovation and Science Regional Government (CTS546 and P10-CTS-05704) and the Jerome Lejeune Foundation (Paris, France). YDDO is the recipient of a Nicolas Monarde contract from the Servicio Andaluz de Salud. Consejería de Salud. Junta de Andalucía.

Journal Article; Research Support, Non-U.S. Gov't; OBJECTIVE Serum levels of soluble TNF-like weak inducer of apoptosis (sTWEAK) and its scavenger receptor CD163 (sCD163) have been linked to insulin resistance. We analysed the usefulness of these cytokines as biomarkers of type 2 diabetes in a Spanish cohort, together with their relationship to food consumption in the setting of the Di@bet.es study. RESEARCH DESIGN AND METHODS This is a cross-sectional, matched case-control study of 514 type 2 diabetes subjects and 517 controls with a Normal Oral Glucose Tolerance Test (NOGTT), using data from the Di@bet.es study. Study variables included clinical and demographic structured survey, food frequency questionnaire and physical examination. Serum concentrations of sTWEAK and sCD163 were measured by ELISA. Linear regression analysis determined which variables were related to sTWEAK and sCD163 levels. Logistic regression analysis was used to estimate odd ratios of presenting type 2 diabetes. RESULTS sCD163 concentrations and sCD163/sTWEAK ratio were 11.0% and 15.0% higher, respectively, (P

This is an open access article distributed under the Creative Commons Attribution License.-- et al., Fragile X syndrome is the most common inherited form of intellectual disability. Here we report on a study based on a collaborative registry, involving 12 Spanish centres, of molecular diagnostic tests in 1105 fragile X families comprising 5062 individuals, of whom, 1655 carried a full mutation or were mosaic, three cases had deletions, 1840 had a premutation, and 102 had intermediate alleles. Two patients with the full mutation also had Klinefelter syndrome. We have used this registry to assess the risk of expansion from parents to children. From mothers with premutation, the overall rate of allele expansion to full mutation is 52.5%, and we found that this rate is higher for male than female offspring (63.6% versus 45.6%; P < 0.001). Furthermore, in mothers with intermediate alleles (45-54 repeats), there were 10 cases of expansion to a premutation allele, and for the smallest premutation alleles (55-59 repeats), there was a 6.4% risk of expansion to a full mutation, with 56 repeats being the smallest allele that expanded to a full mutation allele in a single meiosis. Hence, in our series the risk for alleles of < 59 repeats is somewhat higher than in other published series. These findings are important for genetic counselling. © 2014 María-Isabel Tejada et al., Thanks are due to the agreements between GIRMOGEN and the Real Patronato sobre Discapacidad of the Spain’s Ministry for Health, Social Services and Equality (Spain) to carry out this study.

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OBJETIVE: To report the data of the Home Parenteral Nutrition (HPN) registry of the NADYA-SENPE working group for the years 2011 and 2012. METHODOLOGY: We compiled the data from the on-line registry introduced by reviewers of NADYA group responsible for monitoring of NPD introduced by since January 1, 2011 to december 31, 2012. Included fields were: age, sex, diagnosis and reason for HPN, access path, complications, beginning and end dates, complementary oral or enteral nutrition, activity level, autonomy degree, product and fungible material supply, withdrawal reason and intestinal transplant indication. RESULTS: Year 2010: 184 patients from 29 hospitals , representing a rate of 3.98 patients/million inhabitants/ year 2011, with 186 episodes were recorded NPD . During 2012, 203 patients from 29 hospitals , representing a rate of 4.39 patients/million inhabitants/year 2012 , a total of 211 episodes were recorded NPD . CONCLUSIONS: We observe an increase in registered patients with respect to previous years.Neoplasia remains as the main pathology since 2003. Although NADYA is consolidated registry and has been indispensable source of information relevant to the understanding of the progress of Home Artificial Nutrition in our country, there is ample room for improvement. Especially that refers to the registration of pediatric patients and the registration of complications. Yes Objetivo: Comunicar los datos del registro de Nutrición Parenteral Domiciliaria (NPD) del grupo de trabajo NADYA-SENPE de los años 2011 y 2012. Material y métodos: Recopilación de los datos del registro “on-line” introducidos por los colaboradores del grupo NADYA responsables del seguimiento de la NPD desde el 1 de enero de 2011 al 31 de diciembre de 2012 dividido por años naturales. Resultados: Año 2010: Se registraron 184 pacientes, procedentes de 29 hospitales, lo que representa una tasa de 3,98 pacientes/millón habitantes/año 2011, con 186 episodios de NPD. Durante el año 2012 se registraron 203 pacientes, procedentes de 29 hospitales, lo que representa una tasa de 4,39 pacientes/millón habitantes/año 2012, con un total de 211 episodios de NPD. Conclusiones: Se observa un aumento progresivo de los pacientes registrados respecto a años anteriores. El principal grupo patológico sigue siendo oncológico ocupando el primer lugar desde 2003. Aunque el registro NADYA es un registro consolidado y ha sido y es fuente imprescindible de información relevante para el conocimiento de los avances de la Nutrición Artificial Domiciliaria en nuestro país, queda un amplio margen para la mejora. En especial lo que hace referencia al registro de pacientes pediátricos y al registro de las complicaciones.

We examined the information of legionellosis surveillance system in the municipality of Cordoba (Spain) as a preventive resource for environmental health management and describes the public health implications of sporadic cases investigations. A multidisciplinary team analyzed information on surveillance of water sites potentially contaminated by Legionella and clinical data of the patients classified like community case; mapping patient's home address using geographic information systems (GIS). Legionella pneumophila serogroup 1 was identified in 31 sporadic cases. 53 suspected sources, mainly cooling towers have been investigated. In no event is managed to locate infection source even if poorly maintained systems, structural deficiencies and operational failures were apparent. The use of GIS allowed us to identify two geographic areas where cases are concentrated within one radius of less than 500 meters. The finding of two suspected urban advised to reorient the preventive strategy in public health [ESP] Examinamos la información del sistema de vigilancia de la legionelosis en el municipio de Córdoba (España) como recurso preventivo para la gestión en salud ambiental y se describen las implicaciones en salud pública de la investigación de casos esporádicos. Un equipo multidisciplinar analizó la información sobre vigilancia de instalaciones potencialmente contaminadas por Legionella y los datos clínicos de los pacientes calificados como casos comunitarios; mapeando el domicilio de los enfermos usando Sistemas de Información Geográfica (SIG). Legionella pneumophila serogrupo 1 fue identificada en 31 casos esporádicos. Se investigaron 53 fuentes sospechosas, mayoritariamente torres de refrigeración. En ningún caso se logró encontrar el origen de la infección aunque se evidenciaron sistemas pobremente mantenidos, deficiencias estructurales y fallos operacionales. Se identificaron dos áreas geográficas donde se concentran los casos en un radio menor a 500 metros. El hallazgo de dos zonas urbanas sospechosas aconseja reorientar la estrategia preventiva en salud pública. [FR] Analyse et description des implications en santé publique de la surveillance environnementale réalisée dans la recherche de cas esporádicos de milieu communautaire par legionelosis (LD). Une équipe multidisciplinaire s'a chargé d'obtenir l'information clinique des patients; mapeado du domicile des malades en utilisant GIS, identifier des sources suspectes d'infection et mener à terme des inspections d'installations potentiellement contaminées par Legionella. Legionella pneumophila serogrupo 1 a été détecté moyennant test d'antígeno urinario en 31 cas esporádicos de Legionelosis. L'usage de GIS a permis identifier deux zones géographiques où ils se groupent les cas dans un radio moindre à 500 mètres. Ils s'ont recherchés 53 sources suspectes, majorité tours de réfrigération. S'evidenciaron systèmes pobremente maintenus, déficiences structurales et fautes operacionales. Dans aucun cas s'a remporté trouver l'origine de l'infection. La trouvaille de deux zones urbaines conflictuelles où ils se concentrent les cas communautaires il suggère une réorientation de la stratégie préventive en santé publique. Yes

ObjectiveTo analyse the factors associated with the level of adherence to a Mediterranean dietary pattern in healthy Spanish women before pregnancy.DesignA prospective series of 1175 women. An FFQ validated in Spanish populations served to collect dietary data. The Mediterranean Diet Adherence Index was used to assess the level of adherence to a Mediterranean diet pattern. Polytomic regression was performed to identify the associated factors.SettingCatchment area of Virgen de las Nieves University Hospital, Andalusia, Spain.SubjectsThe women were invited to participate in the study at the 20th–22nd gestational week. The selection criteria were: Spanish nationality, 18 years of age or older, singleton pregnancy and absence of health problems that required modifying the diet or physical activity.ResultsAn inverse relationship was found between women's age and level of adherence to a Mediterranean diet pattern, with a clear dose–response association: a younger age entailed worse adherence (P < 0·001). The habit of smoking and sedentary lifestyle had a positive relationship with low adherence, giving OR = 5·36 (95 % 1·91, 15·07) for women who smoked >20 cigarettes/d and OR = 2·07 (95 % CI 1·34, 3·17) for sedentary women. Higher age, higher educational level, and higher social class of the women were associated with a higher level of adherence to the Mediterranean diet (P < 0·001).ConclusionsIn our sample population, younger age, lower social class, primary educational level and elements of an unhealthy lifestyle such as smoking and lack of exercise were associated with low adherence to a Mediterranean diet.

Journal Article; Knowledge on the patterns of repetition amongst individuals who develop language deficits in association with right hemisphere lesions (crossed aphasia) is very limited. Available data indicate that repetition in some crossed aphasics experiencing phonological processing deficits is not heavily influenced by lexical-semantic variables (lexicality, imageability, and frequency) as is regularly reported in phonologically-impaired cases with left hemisphere damage. Moreover, in view of the fact that crossed aphasia is rare, information on the role of right cortical areas and white matter tracts underpinning language repetition deficits is scarce. In this study, repetition performance was assessed in two patients with crossed conduction aphasia and striatal/capsular vascular lesions encompassing the right arcuate fasciculus (AF) and inferior frontal-occipital fasciculus (IFOF), the temporal stem and the white matter underneath the supramarginal gyrus. Both patients showed lexicality effects repeating better words than non-words, but manipulation of other lexical-semantic variables exerted less influence on repetition performance. Imageability and frequency effects, production of meaning-based paraphrases during sentence repetition, or better performance on repeating novel sentences than overlearned clichés were hardly ever observed in these two patients. In one patient, diffusion tensor imaging disclosed damage to the right long direct segment of the AF and IFOF with relative sparing of the anterior indirect and posterior segments of the AF, together with fully developed left perisylvian white matter pathways. These findings suggest that striatal/capsular lesions extending into the right AF and IFOF in some individuals with right hemisphere language dominance are associated with atypical repetition patterns which might reflect reduced interactions between phonological and lexical-semantic processes. Yes

[Background and Aim] The genotype-phenotype interaction in drug-induced liver injury (DILI) is a subject of growing interest. Previous studies have linked amoxicillin-clavulanate (AC) hepatotoxicity susceptibility to specific HLA alleles. In this study we aimed to examine potential associations between HLA class I and II alleles and AC DILI with regards to phenotypic characteristics, severity and time to onset in Spanish AC hepatotoxicity cases. [Methods] High resolution genotyping of HLA loci A, B, C, DRB1 and DQB1 was performed in 75 AC DILI cases and 885 controls. [Results] The distributions of class I alleles A*3002 (P/Pc = 2.6E-6/5E-5, OR 6.7) and B*1801 (P/Pc = 0.008/0.22, OR 2.9) were more frequently found in hepatocellular injury cases compared to controls. In addition, the presence of the class II allele combination DRB1*1501-DQB1*0602 (P/Pc = 5.1E-4/0.014, OR 3.0) was significantly increased in cholestatic/mixed cases. The A*3002 and/or B*1801 carriers were found to be younger (54 vs 65 years, P = 0.019) and were more frequently hospitalized than the DRB1*1501-DQB1*0602 carriers. No additional alleles outside those associated with liver injury patterns were found to affect potential severity as measured by Hy’s Law criteria. The phenotype frequencies of B*1801 (P/Pc = 0.015/0.42, OR 5.2) and DRB1*0301-DQB1*0201 (P/Pc = 0.0026/0.07, OR 15) were increased in AC DILI cases with delayed onset compared to those corresponding to patients without delayed onset, while the opposite applied to DRB1*1302-DQB1*0604 (P/Pc = 0.005/0.13, OR 0.07). [Conclusions] HLA class I and II alleles influence the AC DILI signature with regards to phenotypic expression, latency presentation and severity in Spanish patients., This study was supported by the research grant Proyecto Excelencia P10-CTS-6470 and by the Agencia Española del Medicamento. CIBERehd and Red Genómica del Cancer are funded by Instituto de Salud Carlos III.

Spanish Group for Nosocomial Infections (GEIH).-- et al., A total of 1,021 extended-spectrum-β-lactamase-producing Escherichia coli (ESBLEC)isolates obtained in 2006 during a Spanish national survey conducted in 44 hospitals were analyzed for the presence of the O25b:H4-B2-ST131 (sequence type 131) clonal group. Overall, 195 (19%) O25b-ST131 isolates were detected, with prevalence rates ranging from 0% to 52% per hospital. Molecular characterization of 130 representative O25b-ST131 isolates showed that 96 (74%) were positive for CTX-M-15, 15 (12%) for CTX-M-14, 9 (7%) for SHV-12, 6 (5%) for CTX-M-9, 5 (4%) for CTX-M-32, and 1 (0.7%) each for CTX-M-3 and the new ESBL enzyme CTX-M-103. The 130 O25b-ST131 isolates exhibited relatively high virulence scores (mean, 14.4 virulence genes). Although the virulence profiles of the O25b-ST131 isolates were fairly homogeneous, they could be classified into four main virotypes based on the presence or absence of four distinctive virulence genes: virotypes A (22%) (afa FM955459 positive, iroN negative, ibeA negative, sat positive or negative), B (31%) (afa FM955459 negative, iroN positive, ibeA negative, sat positive or negative), C (32%) (afa FM955459 negative, iroN negative, ibeA negative, sat positive), and D (13%) (afa FM955459 negative, iroN positive or negative, ibeA positive, sat positive or negative). The four virotypes were also identified in other countries, with virotype C being overrepresented internationally. Correspondingly, an analysis of XbaI macrorestriction profiles revealed four major clusters, which were largely virotype specific. Certain epidemiological and clinical features corresponded with the virotype. Statistically significant virotype-specific associations included, for virotype B, older age and a lower frequency of infection (versus colonization), for virotype C, a higher frequency of infection, and for virotype D, younger age and community-acquired infections. In isolates of the O25b:H4-B2-ST131 clonal group, these findings uniquely define four main virotypes, which are internationally distributed, correspond with pulsed-field gel electrophoresis (PFGE) profiles, and exhibit distinctive clinical-epidemiological associations. Copyright © 2013, American Society for Microbiology., A.M. acknowledges the Ramón y Cajal program from the Spanish Ministerio de Economía y Competitividad, Gobierno de España. R.M. acknowledges the grant of the Agencia Española de Cooperación Internacional (AECI) (Ministerio de Asuntos Exteriores y de Cooperación). This work was partially supported by the Red Española de Investigación en Patología Infecciosa (REIPI) (no. RD06/0008/1018-1016, RD12/0015) and grant no. PI09/01273, 070190, 10/02021, 10/01955, 10/00795, and PI11/01117 (Instituto de Salud Carlos III, Fondo de Investigación Sanitaria, Ministerio de Economía y Competitividad, Gobierno de España), CN2012/303 09TAL007261PR and 10MRU261023PR (Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia and the European Regional Development Fund [ERDF]), 0048/2008 and CTS-5259 (Junta de Andalucía), BFU2011-26608 (Spanish Ministry of Education), 282004/FP7-HEALTH.2011.2.3.1-2 (European VII Framework Program), and FEDERINNTERCONECTA-COLIVAC (CDTI, Ministerio de Economía y Competitividad, Gobierno de España; Consellería de Economía e Industria, Xunta de Galicia; ERDF).

Jose Luis López-Campos,1,2 María Abad Arranz,1 Carmen Calero Acuña,1,2 Fernando Romero Valero,3 Ruth Ayerbe García,4 Antonio Hidalgo Molina,3 Ricardo I Aguilar Perez-Grovas,4 Francisco García Gil,5 Francisco Casas Maldonado,6 Laura Caballero Ballesteros,5 María Sánchez Palop,6 Dolores Pérez-Tejero,7 Alejandro Segado,7 Jose Calvo Bonachera,8 Bárbara Hernández Sierra,8 Adolfo Doménech,9 Macarena Arroyo Varela,9 Francisco González Vargas,10 Juan J Cruz Rueda10 1Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Universidad de Sevilla, Seville, 2Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, 3Hospital Universitario Puerta del Mar, Cádiz, 4Hospital Juan Ramón Jiménez, Huelva, 5Hospital Universitario Reina Sofía, Córdoba, 6Hospital Universitario San Cecilio, Granada, 7Hospital Infanta Margarita, Cabra, Córdoba, 8Hospital Torrecárdenas, Almería, 9Hospital Regional Universitario de Málaga, 10Hospital Universitario Virgen de las Nieves, Granada, Spain Introduction: This study is an analysis of a pilot COPD clinical audit that evaluated adherence to guidelines for patients with COPD in a stable disease phase during a routine visit in specialized secondary care outpatient clinics in order to identify the variables associated with the decision to step-up or step-down pharmacological treatment.Methods: This study was a pilot clinical audit performed at hospital outpatient respiratory clinics in the region of Andalusia, Spain (eight provinces with over eight million inhabitants), in which 20% of centers in the area (catchment population 3,143,086 inhabitants) were invited to participate. Treatment changes were evaluated in terms of the number of prescribed medications and were classified as step-up, step-down, or no change. Three backward stepwise binominal multivariate logistic regression analyses were conducted to evaluate variables associated with stepping up, stepping down, and inhaled corticosteroids discontinuation.Results: The present analysis evaluated 565 clinical records (91%) of the complete audit. Of those records, 366 (64.8%) cases saw no change in pharmacological treatment, while 99patients (17.5%) had an increase in the number of drugs, 55 (9.7%) had a decrease in the number of drugs, and 45 (8.0%) noted a change to other medication for a similar therapeutic scheme. Exacerbations were the main factor in stepping up treatment, as were the symptoms themselves. In contrast, rather than symptoms, doctors used forced expiratory volume in 1second and previous treatment with long-term antibiotics or inhaled corticosteroids as the key determinants to stepping down treatment.Conclusion: The majority of doctors did not change the prescription. When changes were made, a number of related factors were noted. Future trials must evaluate whether these therapeutic changes impact clinically relevant outcomes at follow-up. Keywords: quality of care, outpatient care, treatment strategies, follow-up, respiratory diseases, airway diseases

Journal Article; We aimed to evaluate the correct assignment of HCV genotypes by three commercial methods-Trugene HCV genotyping kit (Siemens), VERSANT HCV Genotype 2.0 assay (Siemens), and Real-Time HCV genotype II (Abbott)-compared to NS5B sequencing. We studied 327 clinical samples that carried representative HCV genotypes of the most frequent geno/subtypes in Spain. After commercial genotyping, the sequencing of a 367 bp fragment in the NS5B gene was used to assign genotypes. Major discrepancies were defined, e.g. differences in the assigned genotype by one of the three methods and NS5B sequencing, including misclassification of subtypes 1a and 1b. Minor discrepancies were considered when differences at subtype levels, other than 1a and 1b, were observed. The overall discordance with the reference method was 34% for Trugene and 15% for VERSANT HCV2.0. The Abbott assay correctly identified all 1a and 1b subtypes, but did not subtype all the 2, 3, 4 and 5 (34%) genotypes. Major discordances were found in 16% of cases for Trugene HCV, and the majority were 1b- to 1a-related discordances; major discordances were found for VERSANT HCV 2.0 in 6% of cases, which were all but one 1b to 1a cases. These results indicated that the Trugene assay especially, and to a lesser extent, Versant HCV 2.0, can fail to differentiate HCV subtypes 1a and 1b, and lead to critical errors in clinical practice for correctly using directly acting antiviral agents. Yes

Journal Article; AIM To investigate the incidence of neoplasms in inflammatory bowel disease (IBD) patients and the potential causative role of thiopurines. METHODS We performed an observational descriptive study comparing the incidence of malignancies in IBD patients treated with thiopurines and patients not treated with these drugs. We included 812 patients which were divided in two groups depending on whether they have received thiopurines or not. We have studied basal characteristics of both groups (age when the disease was diagnosed, sex, type of IBD, etc.) and treatments received (Azathioprine, mercaptopurine, infliximab, adalimumab or other immunomodulators), as well as neoplasms incidence. Univariate analysis was performed with the student t test, χ(2) test or Wilcoxon exact test as appropriate. A logistic regression analysis was performed as multivariate analysis. Statistical significance was establish at P values of less than 0.05, and 95%CI were used for the odds ratios. RESULTS Among 812 patients included, 429 (52.83%) have received thiopurines: 79.5% azathioprine, 14% mercaptopurine and 6.5% both drugs. 44.76% of patients treated with thiopurines and 46, 48% of patients who did not receive this treatment were women (P > 0.05). The proportion of ulcerative colitis patients treated with thiopurines was 30.3% compare to 66. 67% of patients not treated (P < 0.001). Mean azathioprine dose was 123.79 ± 36.5 mg/d (range: 50-250 mg/d), mean usage time was 72.16 ± 55.7 mo (range: 1-300 mo) and the accumulated dose along this time was 274.32 ± 233.5 g (1.5-1350 g). With respect to mercaptopurine, mean dose was 74.7 ± 23.9 mg/d (range: 25-150 mg/d), mean usage time of 23.37 ± 27.6 mo (range: 1-118 mo), and the accumulated dose along this time was 52.2 ± 63.5 g (range: 1.5-243 g). Thiopurine S-methyltransferase activity was tested in 66% of patients treated with thiopurines, among which 98.2% had an intermediate or high activity. Among the patients treated with thiopurines, 27.27% (112 patients) and 11.66% (50 patients) received treatment with Infliximab and Adalimumab respectively, but only 1.83% (7 patients) and 0.78% (3 patients) received these drugs in the group of patients who did not received thiopurines (P < 0.001 and P < 0.001 respectively). Finally, 6.8% (29 patients) among those treated with thiopurines have received other immunesupresants (Methotrexate, Tacrolimus, Cyclosporin), compare to 1% (4 patients) of patients not treated with thiopurines (P < 0.001). Among patients treated with thiopurines, 3.97% developed a malignancy, and among those not treated neoplasms presented in 8.1% (P = 0.013). The most frequent neoplasms were colorectal ones (12 cases in patients not treated with thiopurines but none in treated, P < 0.001) followed by non-melanoma skin cancer (8 patients in treated with thiopurines and 6 in not treated, P > 0.05). CONCLUSION In our experience, thiopurine therapy did not increase malignancies development in IBD patients, and was an efective and safe treatment for these diseases. Yes

Journal Article; Research Support, Non-U.S. Gov't; Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is an autosomal recessive tubular disorder characterized by excessive renal magnesium and calcium excretion and chronic kidney failure. This rare disease is caused by mutations in the CLDN16 and CLDN19 genes. These genes encode the tight junction proteins claudin-16 and claudin-19, respectively, which regulate the paracellular ion reabsorption in the kidney. Patients with mutations in the CLDN19 gene also present severe visual impairment. Our goals in this study were to examine the clinical characteristics of a large cohort of Spanish patients with this disorder and to identify the disease causing mutations. We included a total of 31 patients belonging to 27 unrelated families and studied renal and ocular manifestations. We then analyzed by direct DNA sequencing the coding regions of CLDN16 and CLDN19 genes in these patients. Bioinformatic tools were used to predict the consequences of mutations. Clinical evaluation showed ocular defects in 87% of patients, including mainly myopia, nystagmus and macular colobomata. Twenty two percent of patients underwent renal transplantation and impaired renal function was observed in another 61% of patients. Results of the genetic analysis revealed CLDN19 mutations in all patients confirming the clinical diagnosis. The majority of patients exhibited the previously described p.G20D mutation. Haplotype analysis using three microsatellite markers showed a founder effect for this recurrent mutation in our cohort. We also identified four new pathogenic mutations in CLDN19, p.G122R, p.I41T, p.G75C and p.G75S. A strategy based on microsequencing was designed to facilitate the genetic diagnosis of this disease. Our data indicate that patients with CLDN19 mutations have a high risk of progression to chronic renal disease. Yes

Journal Article; Research Support, Non-U.S. Gov't; We present early estimates of influenza vaccine effectiveness (VE) in the population targeted for vaccination, during 25 December 2011 to 19 February 2012. The adjusted VE was 55% (95% CI: 3 to 79) against any type of influenza virus and 54% (95% CI: 1 to 79) against influenza A(H3N2) virus. This suggests a moderate protective effect of the vaccine in the targeted population in a late influenza epidemic with limited match between vaccine and circulating strains. Yes

Objectives: To describe the clinical presentation and prognosis of elderly adults hospitalized with pandemic 2009 A(H1N1) influenza infection and to compare these data with those of younger patients. Design: Prospective, observational, multicenter study. Setting: Thirteen hospitals in Spain. Participants: Adults admitted to the hospital with confirmed pandemic 2009 A(H1N1) influenza infection. Measurements: Demographic, clinical, laboratory, radiological, and outcome variables. Results: Between June 12 and November 10, 2009, 585 adults with confirmed 2009 A(H1N1) influenza were hospitalized, of whom 50 (8.5%) were aged 65 and older (median age 72, range 65�87). Older adults (?65) were more likely to have associated comorbidities (88.0% vs 51.2%; P < .001), primarily chronic pulmonary diseases (46.0% vs 27.3%; P < .001). Lower respiratory tract symptoms and signs such as dyspnea (60.0% vs 45.6%) and wheezing (46.0% vs 27.8%; P = .007) were also more common in these elderly adults, although pulmonary infiltrates were present in just 14 (28.0%) of the older adults, compared with 221 (41.3%) of the younger adults (P = .06). Multilobar involvement was less frequent in elderly adults with pulmonary infiltrates than younger adults with pulmonary infiltrates (21.4% vs 60.0%; P = .05). Rhinorrhea (4.0% vs 21.9%; P = .003), myalgias (42.0% vs 59.1%; P = .01), and sore throat (14.0% vs 29.2%; P = .02) were more frequent in younger adults. Early antiviral therapy (

Objective. To evaluate the association between diabetes mellitus and health-related quality of life (HRQOL) controlled for several sociodemographic and anthropometric variables, in a representative sample of the Spanish population.Methods. A population-based, cross-sectional, and cluster sampling study, with the entire Spanish population as the target population. Five thousand and forty-seven participants (2162/2885 men/women) answered the HRQOL short form 12-questionnaire (SF-12). The physical (PCS-12) and the mental component summary (MCS-12) scores were assessed. Subjects were divided into four groups according to carbohydrate metabolism status: normal, prediabetes, unknown diabetes (UNKDM), and known diabetes (KDM). Logistic regression analyses were conducted.Results. Mean PCS-12/MCS-12 values were50.9±8.5/47.6±10.2, respectively. Men had higher scores than women in both PCS-12 (51.8±7.2versus50.3±9.2;P<0.001) and MCS-12 (50.2±8.5versus45.5±10.8;P<0.001). Increasing age and obesity were associated with a poorer PCS-12 score. In women lower PCS-12 and MCS-12 scores were associated with a higher level of glucose metabolism abnormality (prediabetes and diabetes), (P<0.0001for trend), but only the PCS-12 score was associated with altered glucose levels in men (P<0.001for trend). The Odds Ratio adjusted for age, body mass index (BMI) and educational level, for a PCS-12 score below the median was 1.62 (CI 95%: 1.2–2.19;P<0.002) for men with KDM and 1.75 for women with KDM (CI 95%: 1.26–2.43;P<0.001), respectively.Conclusion. Current study indicates that increasing levels of altered carbohydrate metabolism are accompanied by a trend towards decreasing quality of life, mainly in women, in a representative sample of Spanish population.

Journal Article; INTRODUCTION Selenium is an essential micronutrient for human health, being a cofactor for enzymes with antioxidant activity that protect the organism from oxidative damage. An inadequate intake of this mineral has been associated with the onset and progression of chronic diseases such as hypertension, diabetes, coronary diseases, asthma, and cancer. For this reason, knowledge of the plasma and erythrocyte selenium levels of a population makes a relevant contribution to assessment of its nutritional status. OBJECTIVE The objective of the present study was to determine the nutritional status of selenium and risk of selenium deficiency in a healthy adult population in Spain by examining food and nutrient intake and analyzing biochemical parameters related to selenium metabolism, including plasma and erythrocyte levels and selenium-dependent glutathione peroxidase (GPx) enzymatic activity. MATERIAL AND METHODS We studied 84 healthy adults (31 males and 53 females) from the province of Granada, determining their plasma and erythrocyte selenium concentrations and the association of these levels with the enzymatic activity of glutathione peroxidase (GPx) and with life style factors. We also gathered data on their food and nutrient intake and the results of biochemical analyses. Correlations were studied among all of these variables. RESULTS The mean plasma selenium concentration was 76.6 ± 17.3 μg/L (87.3 ± 17.4 μg/L in males, 67.3 ± 10.7 μg/L in females), whereas the mean erythrocyte selenium concentration was 104.6 μg/L (107.9 ± 26.1 μg/L in males and 101.7 ± 21.7 μg/L in females). The nutritional status of selenium was defined by the plasma concentration required to reach maximum GPx activity, establishing 90 μg/L as reference value. According to this criterion, 50% of the men and 53% of the women were selenium deficient. CONCLUSIONS Selenium is subjected to multiple regulation mechanisms. Erythrocyte selenium is a good marker of longer term selenium status, while plasma selenium appears to be a marker of short-term nutritional status. The present findings indicate a positive correlation between plasma selenium concentration and the practice of physical activity. Bioavailability studies are required to establish appropriate reference levels of this mineral for the Spanish population. Yes Introducción: El selenio es un micronutriente esencial para la salud del ser humano, debido fundamentalmente a su implicación como cofactor de enzimas con actividad antioxidante que protegen al organismo del daño oxidativo, de modo que una ingesta inadecuada de este mineral está asociada con la aparición y desarrollo de enfermedades crónicas tales como hipertensión, diabetes, enfermedades coronarias,asma y cáncer. Por esta razón, la determinación de selenio plasmático y eritrocitario contribuirá a la valoración del estado nutricional de la población estudiada. Objetivo: El objetivo de estudio fue valorar el estado nutricional de selenio en una población adulta sana en riesgo de deficiencia, a través de una evaluación de la ingesta, así como de los niveles de selenio en plasma y eritrocito, y la actividad de la enzima selenio-dependiente Glutation Peroxidasa (GPx) en eritrocito. Material y métodos: El estudio se realizó en un grupo de población de 84 adultos sanos pertenecientes a la provincia de Granada (31 hombres y 53 mujeres) en los que se determinó la ingesta de nutrientes y selenio, sus niveles plasmáticos y eritrocitarios, así como su asociación con la actividad de la enzima Glutation Peroxidasa y con diversos factores del estilo de vida. Resultados: Las concentraciones medias de selenio en plasma fueron de 76,6 ± 17,3 μg/L (87,3 ± 17,4 μg/L en los hombres, y de 67,3 ± 10,7 μg/L para las mujeres), mientras que los valores eritrocitarios de selenio de la población total del estudio fue de 104,6 μg/L (107,9 ± 26,1 μg/L en hombres y 101,7 ± 21,7 μg/L en mujeres). La evaluación del estado nutricional de selenio, se realizo en función de la concentración en plasma necesaria para alcanzar la máxima actividad de GPx, estableciendo como valor de referencia 90 μg/L, observamos que el 50% de los hombres y el 53% de las mujeres se encuentran en situación de deficiencia. Conclusiones: El selenio es un mineral sujeto a múltiples mecanismos de regulación. El selenio eritrocitario es un buen indicador del estatus mineral de selenio a largo plazo, mientras que el selenio plasmático es un indicador de estatus nutricional de selenio a corto plazo. Los resultados obtenidos mostraron una correlación positiva entre los niveles de selenio en plasma y la realización de actividad física. Es necesario disponer de más estudios de biodisponibilidad de selenio con el fin de poder establecer niveles de referencia de este mineral para la población española.

Journal Article; BACKGROUND: The overall intake of energy and nutrients in the Granada EPIC-cohort (European Prospective Investigation into Cancer and Nutrition) is examined in order to assess compliance with the Spanish Nutritional Objectives (NO) and the Recommended Intakes (RI). METHODS: During recruitment (1992-1996), 7,789 participants, aged 35-69, were asked about diet through a validated diet history questionnaire. Nutrient intake is compared to the NO and RI that were valid at that time. Risk of inadequate intake is estimated as the percentage of the sample with intakes: ≤ 1/3 RI (high risk), ≤ 2/3 RI- > 1/3 RI (moderate risk), ≤ RI- > 2/3 RI, > RI. Differences in intakes have been analyzed by sex and age, and by smoking status and BMI. RESULTS: The daily intake of nutrients did not meet the NO as the total contribution of energy from proteins and fats exceeded these guidelines. Whilst intake of most nutrients was above the RI, the amount of iron, magnesium and vitamins D and E provided by the diet was not enough to meet the RI: in women aged 20-49 years, about 55% were at moderate risk for iron inadequacy, and a 20% of women for magnesium. Both sexes were at high risk of inadequacy for vitamin D, although sunlight exposure may supply adequate amounts. Never smokers showed a higher compliance to the NO. CONCLUSION: At recruitment, the nutrient profile of the diet was unbalanced. The observed nutrient inadequacy for iron, magnesium and vitamin E might be attributed to inappropriate dietary habits, and may have implications for future disease risk. Yes Introducción: Se ha evaluado la ingesta de energía y de nutrientes de la cohorte EPIC-Granada (Estudio Prospectivo Europeo sobre Nutrición y Cáncer) en relación con la adecuación a los Objetivos Nutricionales españoles(ON) y a las ingestas recomendadas (IR). Métodos: Durante el reclutamiento (1992-1996), 7,789 participantes (de 35-69 años de edad) fueron entrevistados sobre su dieta mediante el método de historia de dieta. La ingesta de nutrientes se ha comparado con los NO y con las IR. El riesgo de ingesta inadecuada se ha estimado como porcentaje de participantes con ingestas: ≤ 1/3 IR (riesgo elevado), ≤ 2/3 IR-> 1/3 IR (riesgo moderado), ≤ IR-> 2/3 IR, > IR. Se han analizado diferencias según sexo, edad, hábito tabáquico e Índice de Masa Corporal(IMC). Resultados: La ingesta dietética no cumple los ON debido a que la contribución de proteínas y lípidos sobre la ingesta energética total excede estas recomendaciones. La mayoría de los nutrientes satisfacen las IR, excepto hierro, magnesio, vitamina D y E: entre las mujeres de 20-49 años un 55% presentaron riesgo moderado de ingesta inadecuada de hierro, y un 20% lo presentaron para el magnesio. En ambos sexos se encontró un elevado riesgo de ingesta inadecuada de vitamina D, que puede compensarse por la exposición solar. Los no fumadores mostraron un mejor cumplimiento de los ON. Conclusión: El perfil calórico de la dieta en la cohorte EPIC está desequilibrado. La ingesta inadecuada de los nutrientes hierro, magnesio y vitamina E podría ser atribuible a hábitos dietéticos inadecuados, y podría tener implicaciones para el desarrollo futuro de enfermedades.

The impact of antimicrobial resistance on clinical outcomes is the subject of ongoing investigations, although uncertainty remains about its contribution to mortality. We investigated the impact of carbapenem resistance on mortality in Pseudomonas aeruginosa bacteremia in a prospective multicenter (10 teaching hospitals) observational study of patients with monomicrobial bacteremia followed up for 30 days after the onset of bacteremia. The adjusted influence of carbapenem resistance on mortality was studied by using Cox regression analysis. Of 632 episodes, 487 (77%) were caused by carbapenem-susceptible P. aeruginosa (CSPA) isolates, and 145 (23%) were caused by carbapenem-resistant P. aeruginosa (CRPA) isolates. The median incidence density of nosocomial CRPA bacteremia was 2.3 episodes per 100,000 patient-days (95% confidence interval [CI], 1.9 to 2.8). The regression demonstrated a time-dependent effect of carbapenem resistance on mortality as well as a significant interaction with the Charlson index: the deleterious effect of carbapenem resistance on mortality decreased with higher Charlson index scores. The impact of resistance on mortality was statistically significant only from the fifth day after the onset of the bacteremia, reaching its peak values at day 30 (adjusted hazard ratio for a Charlson score of 0 at day 30, 9.9 [95% CI, 3.3 to 29.4]; adjusted hazard ratio for a Charlson score of 5 at day 30, 2.6 [95% CI, 0.8 to 8]). This study clarifies the relationship between carbapenem resistance and mortality in patients with P. aeruginosa bacteremia. Although resistance was associated with a higher risk of mortality, the study suggested that this deleterious effect may not be as great during the first days of the bacteremia or in the presence of comorbidities.

Streptococcus pneumoniae remains an important cause of bacteremia worldwide. Last years, a decrease of S. pneumoniae penicillin- resistant isolates has been observed. The objec- tive of this study was to describe the episodes of bacteremia due to S. pneumoniaeduring a peri- od of 11 years. Epidemiological and clinical data, serotypes causing bacteremia, antibiotic susceptibility and prognosis factors were stud- ied. Over a period of 11 years, all the episodes of S. pneumoniaebacteremia were analysed. Their clinical and microbiological features were recorded. Statistical analysis was carried out to determine risk factors for pneumococcal bac- teremia and predictors of fatal outcome. Finally, 67 S. pneumoniae bacteremia episodes were included in this study. The majority of cases were produced in white men in the middle age of their life. The main predisposing factors observed were smoking, antimicrobial and/or corticosteroids administration, chronic pul- monary obstructive disease and HIV infection, and the most common source of bacteremia was the low respiratory tract. The main serotypes found were 19A, 1, 14 and 7F. Seventy-seven per- cent of these isolates were penicillin-suscepti- ble, and the mortality in this serie was really low. Statistical significance was observed between age, sex and race factors and the pres- ence of bacteremia, and there was relationship between the patient's condition and the out- come. In our study, S. pneumoniaebacteremia is mainly from community-acquired origin mainly caused in men in the median age of the life. 40% of bacteremias were caused by serotypes 19A, 1, 7F and 14. During the period of study the incidence of bacteremia was stable and the mortality rate was very low. In adults, the majority of cases of pneumococcal bacteremia are asso- ciated with pneumonia, while in children the primary site of infection is frequently unknown. The overall mortality rate for pneu- mococcal bacteremia is 15-20% among adults, with the rate increasing to 30-40% among eld- erly patients. Since introduction of the 7-valent pneumo- coccal conjugate vaccine (PCV7), the estimat- ed annual incidence of invasive disease (including bacteremia) in the USA has decreased. 4 However, together with reduction in invasive disease due to serotypes encom- passed in PCV7, non PCV7 serotypes have emerged. 5 Moreover, for several reasons, a decrease of S. pneumoniae penicillin-resistant strains has been observed last years world- wide. Clearly, there is a need for evaluation the new serotypes related with these episodes, the susceptibility evolution to penicillin and other antibiotics and clinical aspects to this infec- tion. Thus, the aim of this study was to describe the episodes of bacteremia due to S. pneumoniae during a period of 11 years in our health area. Epidemiological and clinical data, serotypes causing bacteremia and prognosis factors were analysed.

Background Persons with schizophrenia and related disorders may be particularly sensitive to a number of determinants of service use, including those related with illness, socio-demographic characteristics and organizational factors. The objective of this study is to identify factors associated with outpatient contacts at community mental health services of patients with schizophrenia or related disorders. Methods This cross-sectional study analyzed 1097 patients. The main outcome measure was the total number of outpatient consultations during one year. Independent variables were related to socio-demographic, clinical and use of service factors. Data were collected from clinical records. Results The multilevel linear regression model explained 46.35% of the variance. Patients with significantly more contacts with ambulatory services were not working and were receiving welfare benefits (p = 0.02), had no formal education (p = 0.02), had a global level of severity of two or three (four being the most severe) (p < 0.001), with one or more inpatient admissions (p < 0.001), and in contact with both types of professional (nurses and psychiatrists) (p < 0.001). The patients with the fewest ambulatory contacts were those with diagnoses of persistent delusional disorders (p = 0.04) and those who were attended by four of the 13 psychiatrists (p < 0.001). Conclusions As expected, the variables that explained the use of community service could be viewed as proxies for severity of illness. The most surprising finding, however, was that a group of four psychiatrists was also independently associated with use of ambulatory services by patients with schizophrenia or related disorders. More research is needed to carefully examine how professional support networks interact to affect use of mental health.