DAS-28-based EULAR response and HAQ improvement in rheumatoid arthritis patients switching between TNF antagonists

INTRODUCTION No definitive data are available regarding the value of switching to an alternative TNF antagonist in rheumatoid arthritis patients who fail to respond to the first one. The aim of this study was to evaluate treatment response in a clinical setting based on HAQ improvement and EULAR response criteria in RA patients who were switched to a second or a third TNF antagonist due to failure with the first one. METHODS This was an observational, prospective study of a cohort of 417 RA patients treated with TNF antagonists in three university hospitals in Spain between January 1999 and December 2005. A database was created at the participating centres, with well-defined operational instructions. The main outcome variables were analyzed using parametric or non-parametric tests depending on the level of measurement and distribution of each variable. RESULTS Mean (+/- SD) DAS-28 on starting the first, second and third TNF antagonist was 5.9 (+/- 2.0), 5.1 (+/- 1.5) and 6.1 (+/- 1.1). At the end of follow-up, it decreased to 3.3 (+/- 1.6; Delta = -2.6; p > 0.0001), 4.2 (+/- 1.5; Delta = -1.1; p = 0.0001) and 5.4 (+/- 1.7; Delta = -0.7; p = 0.06). For the first TNF antagonist, DAS-28-based EULAR response level was good in 42% and moderate in 33% of patients. The second TNF antagonist yielded a good response in 20% and no response in 53% of patients, while the third one yielded a good response in 28% and no response in 72%. Mean baseline HAQ on starting the first, second and third TNF antagonist was 1.61, 1.52 and 1.87, respectively. At the end of follow-up, it decreased to 1.12 (Delta = -0.49; p < 0.0001), 1.31 (Delta = -0.21, p = 0.004) and 1.75 (Delta = -0.12; p = 0.1), respectively. Sixty four percent of patients had a clinically important improvement in HAQ (defined as > or = -0.22) with the first TNF antagonist and 46% with the second. CONCLUSION A clinically significant effect size was seen in less than half of RA patients cycling to a second TNF antagonist.

High Prevalence of Systemic Autoimmune Diseases in Patients with Meniere's Disease

BACKGROUND. Autoimmunity appears to be associated with the pathophysiology of Meniere's disease (MD), an inner ear disorder characterized by episodes of vertigo associated with hearing loss and tinnitus. However, the prevalence of autoimmune diseases (AD) in patients with MD has not been studied in individuals with uni or bilateral sensorineural hearing loss (SNHL). METHODS AND FINDINGS. We estimated the prevalence of AD in 690 outpatients with MD with uni or bilateral SNHL from otoneurology clinics at six tertiary referral hospitals by using clinica criteria and an immune panel (lymphocyte populations, antinuclear antibodies, C3, C4 and proinflammatory cytokines TNFα, INFγ). The observed prevalence of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and ankylosing spondylitis (AS) was higher than expected for the general population (1.39 for RA, 0.87 for SLE and 0.70 for AS, respectively). Systemic AD were more frequently observed in patients with MD and diagnostic criteria for migraine than cases with MD and tension-type headache (p = 0.007). There were clinical differences between patients with uni or bilateral SNHL, but no differences were found in the immune profile. Multiple linear regression showed that changes in lymphocytes subpopulations were associated with hearing loss and persistence of vertigo, suggesting a role for the immune response in MD. CONCLUSIONS. Despite some limitations, MD displays an elevated prevalence of systemic AD such as RA, SLE and AS. This finding, which suggests an autoimmune background in a subset of patients with MD, has important implications for the treatment of MD.

Human Exposure to Endocrine-Disrupting Chemicals and Prenatal Risk Factors for Cryptorchidism and Hypospadias: A Nested Case-Control Study

BACKGROUND. Exposure to xenoestrogens during pregnancy may disturb the development and function of male sexual organs. OBJECTIVE. In this study we aimed to determine whether the combined effect of environmental estrogens measured as total effective xenoestrogen burden (TEXB) is a risk factor for male urogenital malformations. METHODS. In a case-control study, nested in a mother-child cohort (n = 702) established at Granada University Hospital, we compared 50 newborns with diagnosis of cryptorchidism and/or hypospadias with 114 boys without malformations matched by gestational age, date of birth, and parity. Controls did not differ from the total cohort in confounding variables. TEXB and levels of 16 organochlorine pesticides were measured in placenta tissues. Characteristics of parents, pregnancy, and birth were gathered by questionnaire. We used conditional and unconditional regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS. TEXB from organohalogenated compounds was detectable in 72% and 54% of case and control placentas, respectively. Compared with controls, cases had an OR for detectable versus non-detectable TEXB of 2.82 (95% CI, 1.10-7.24). More pesticides were detected in cases than in controls (9.34 +/- 3.19 vs. 6.97 +/- 3.93). ORs for cases with detectable levels of pesticides, after adjusting for potential confounders in the conditional regression analysis, were o,p'-DDT (OR = 2.25; 95% CI, 1.03-4.89), p,p'-DDT (OR = 2.63; 95% CI, 1.21-5.72), lindane (OR = 3.38; 95% CI, 1.36-8.38), mirex (OR = 2.85; 95% CI, 1.22-6.66), and endosulfan alpha (OR = 2.19; 95% CI, 0.99-4.82). Engagement of mothers in agriculture (OR = 3.47; 95% CI, 1.33-9.03), fathers' occupational exposure to xenoestrogens (OR = 2.98; 95% CI, 1.11-8.01), and history of previous stillbirths (OR = 4.20; 95% CI, 1.11-16.66) were also associated with risk of malformations. CONCLUSIONS We found an increased risk for male urogenital malformations related to the combined effect of environmental estrogens in placenta.

The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA

The molecular basis underlying the aberrant DNA-methylation patterns in human cancer is largely unknown. Altered DNA methyltransferase (DNMT) activity is believed to contribute, as DNMT expression levels increase during tumorigenesis. Here, we present evidence that the expression of DNMT3b is post-transcriptionally regulated by HuR, an RNA-binding protein that stabilizes and/or modulates the translation of target mRNAs. The presence of a putative HuR-recognition motif in the DNMT3b 3'UTR prompted studies to investigate if this transcript associated with HuR. The interaction between HuR and DNMT3b mRNA was studied by immunoprecipitation of endogenous HuR ribonucleoprotein complexes followed by RT-qPCR detection of DNMT3b mRNA, and by in vitro pulldown of biotinylated DNMT3b RNAs followed by western blotting detection of HuR. These studies revealed that binding of HuR stabilized the DNMT3b mRNA and increased DNMT3b expression. Unexpectedly, cisplatin treatment triggered the dissociation of the [HuR-DNMT3b mRNA] complex, in turn promoting DNMT3b mRNA decay, decreasing DNMT3b abundance, and lowering the methylation of repeated sequences and global DNA methylation. In summary, our data identify DNMT3b mRNA as a novel HuR target, present evidence that HuR affects DNMT3b expression levels post-transcriptionally, and reveal the functional consequences of the HuR-regulated DNMT3b upon DNA methylation patterns.

Assessment of Severe Apnoea through Voice Analysis, Automatic Speech, and Speaker Recognition Techniques

This study is part of an ongoing collaborative effort between the medical and the signal processing communities to promote research on applying standard Automatic Speech Recognition (ASR) techniques for the automatic diagnosis of patients with severe obstructive sleep apnoea (OSA). Early detection of severe apnoea cases is important so that patients can receive early treatment. Effective ASR-based detection could dramatically cut medical testing time. Working with a carefully designed speech database of healthy and apnoea subjects, we describe an acoustic search for distinctive apnoea voice characteristics. We also study abnormal nasalization in OSA patients by modelling vowels in nasal and nonnasal phonetic contexts using Gaussian Mixture Model (GMM) pattern recognition on speech spectra. Finally, we present experimental findings regarding the discriminative power of GMMs applied to severe apnoea detection. We have achieved an 81% correct classification rate, which is very promising and underpins the interest in this line of inquiry.

Differential prefrontal-like deficit in children after cerebellar astrocytoma and medulloblastoma tumor

BACKGROUND This study was realized thanks to the collaboration of children and adolescents who had been resected from cerebellar tumors. The medulloblastoma group (CE+, n = 7) in addition to surgery received radiation and chemotherapy. The astrocytoma group (CE, n = 13) did not receive additional treatments. Each clinical group was compared in their executive functioning with a paired control group (n = 12). The performances of the clinical groups with respect to controls were compared considering the tumor's localization (vermis or hemisphere) and the affectation (or not) of the dentate nucleus. Executive variables were correlated with the age at surgery, the time between surgery-evaluation and the resected volume. METHODS The executive functioning was assessed by means of WCST, Complex Rey Figure, Controlled Oral Word Association Test (letter and animal categories), Digits span (WISC-R verbal scale) and Stroop test. These tests are very sensitive to dorsolateral PFC and/or to medial frontal cortex functions. The scores for the non-verbal Raven IQ were also obtained. Direct scores were corrected by age and transformed in standard scores using normative data. The neuropsychological evaluation was made at 3.25 (SD = 2.74) years from surgery in CE group and at 6.47 (SD = 2.77) in CE+ group. RESULTS The Medulloblastoma group showed severe executive deficit (

MAPI: towards the integrated exploitation of bioinformatics Web Services.

BACKGROUND. Bioinformatics is commonly featured as a well assorted list of available web resources. Although diversity of services is positive in general, the proliferation of tools, their dispersion and heterogeneity complicate the integrated exploitation of such data processing capacity. RESULTS. To facilitate the construction of software clients and make integrated use of this variety of tools, we present a modular programmatic application interface (MAPI) that provides the necessary functionality for uniform representation of Web Services metadata descriptors including their management and invocation protocols of the services which they represent. This document describes the main functionality of the framework and how it can be used to facilitate the deployment of new software under a unified structure of bioinformatics Web Services. A notable feature of MAPI is the modular organization of the functionality into different modules associated with specific tasks. This means that only the modules needed for the client have to be installed, and that the module functionality can be extended without the need for re-writing the software client. CONCLUSIONS. The potential utility and versatility of the software library has been demonstrated by the implementation of several currently available clients that cover different aspects of integrated data processing, ranging from service discovery to service invocation with advanced features such as workflows composition and asynchronous services calls to multiple types of Web Services including those registered in repositories (e.g. GRID-based, SOAP, BioMOBY, R-bioconductor, and others).

Is a Virtual Library cost effective?

The Andalusian Public Health System Virtual Library (Biblioteca Virtual del Sistema Sanitario Público de Andalucía, BV-SSPA), was created in June 2006. In this paper an evaluation is made to see whether the investment made by the Andalusian Government has been worthwhile. The cost-effectiveness and efficiency of the project together with the management criteria are explored.

NUTRISOL: un programa informático para la evaluación nutricional comunitaria y hospitalaria de acceso libre.

We have developed the computer programme NUTRISOL, a nutritional programme destined to analysis of dietary intake by means of the food transformation to nutrient. It has been performed under Windows operative system, using Visual Basic 6.0. It is presented in a CD-Rom. We have used the Spanish CSIC Food Composition Table and domestic food measures commonly used in Spain which could be modified and updated. Diverse kind of diets and reference anthropometric data are also presented. The results may be treated using various statistical programmes. The programme contains three modules: 1) Nutritional epidemiology, which allows to create or open a data base, sample management, analyse food intake, consultation of nutrient content and exportation of data to statistical programmes. 2) Analyses of diets and recipes, creation or modification of new ones. 3) To ask different diets for prevalent pathologies. Independent tools for modifying the original tables, calculate energetic needs, recommend nutrient intake and anthropometric indexes are also offered. In conclusion, NUTRISOL Programme is an application which runs in PC computers with minimal equipment in a friendly interface, of easy use, freeware, which may be adapted to each country, and has demonstrated its usefulness and reliability in different epidemiologic studies. Furthermore, it may become an efficient instrument for clinical nutrition and health promotion.

Thin healthy women have a similar low bone mass to women with anorexia nervosa.

An association between anorexia nerviosa (AN) and low bone mass has been demonstrated. Bone loss associated with AN involves hormonal and nutritional impairments, though their exact contribution is not clearly established. We compared bone mass in AN patients with women of similar weight with no criteria for AN, and a third group of healthy, normal-weight, age-matched women. The study included forty-eight patients with AN, twenty-two healthy eumenorrhoeic women with low weight (LW group; BMI < 18.5 kg/m2) and twenty healthy women with BMI >18.5 kg/m2 (control group), all of similar age. We measured lean body mass, percentage fat mass, total bone mineral content (BMC) and bone mineral density in lumbar spine (BMD LS) and in total (tBMD). We measured anthropometric parameters, leptin and growth hormone. The control group had greater tBMD and BMD LS than the other groups, with no differences between the AN and LW groups. No differences were found in tBMD, BMD LS and total BMC between the restrictive (n 25) and binge-purge type (n 23) in AN patients. In AN, minimum weight (P = 0.002) and percentage fat mass (P = 0.02) explained BMD LS variation (r2 0.48) and minimum weight (r2 0.42; P = 0.002) for tBMD in stepwise regression analyses. In the LW group, BMI explained BMD LS (r2 0.72; P = 0.01) and tBMD (r2 0.57; P = 0.04). We concluded that patients with AN had similar BMD to healthy thin women. Anthropometric parameters could contribute more significantly than oestrogen deficiency in the achievement of peak bone mass in AN patients.

Kallikrein genes are associated with lupus and glomerular basement membrane-specific antibody-induced nephritis in mice and humans.

Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody-induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that maybe responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody-induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family,which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody-induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms,some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody-induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody-induced nephritis and lupus.

Estudio bibliométrico de la revista Nutrición Hospitalaria en el periodo 2001 a 2005: Parte I, Análisis de la producción científica.

OBJECTIVE To assess the scientific activity and information production of the journal Nutrición Hospitalaria, for the period 2001-2005 by means of a Bibliometric study. METHOD Cross-sectional descriptive study of the results obtained from the analysis of the articles published in the journal Nutrición Hospitalaria. The data were obtained by consulting the electronic version through the Web. In those cases in which there was a link breakdown, and thus, the inability to have access to the electronic document the printed version was consulted. All the documental possibilities were taken into account with the exception of communications to congresses. RESULTS A total of 345 articles were published, 187 (54.20%) being original articles. The geographical distribution of the first author was Spanish in 287 articles (83.19%) and Latin American in 27 (7.83%). Most of the articles are from health care centers (172 articles (49.86%)), and the cooperation index being 4.15. Madrid is the most productive province, for both the absolute and adjusted frequencies. The median number of references per article is 18, the mean being 23.52 (95% CI 20.93 - 26.10). The predominant language was Spanish, with 308 articles (89.28%). CONCLUSION Nutrición Hospitalaria may be considered as a reference journal regarding information and scientific communication on Nutrition for both the Spanish and Latin American communities. The bibliometric parameters studied compare with those verified for the remaining top of the list Spanish scientific journals on health sciences.

Estudio bibliométrico de la revista Nutrición Hospitalaria en el periodo 2001 a 2005: parte 2, análisis de consumo; las referencias bibliográficas.

OBJECTIVE To describe and assess the consumption of the information consulted and cited in the articles published in the journal Nutrición Hospitalaria for the period 2001--2005 by means of bibliometric analysis. METHOD Cross-sectional descriptive analysis of the results obtained from the analysis of the lists of bibliographic references of the articles published at Nutrición Hospitalaria. We studied the most cited journals, the signatures index, the type of document referred, the publication language, the distribution of geographical origin, and obsolescence and readiness index. We took into account all types of documents with the exception of Communications to Congresses. RESULTS 345 articles were published at Nutr Hosp, containing 8,113 bibliographic references, with a median of 18, a maximum of 136 and minimum of 0 BR per article. The mean (rate of publications per published article during the specified period) is 23.52 (95% IC 20.93-26.10) and the mean at 5% is 20.66 per article. The 25th and 75th percentiles are 6 and 32, respectively, the interquartile interval being 26 BR per document. The semi-period of Burton and Kebler is 7 years and the Price Index is 38.18%. CONCLUSION The bibliographic references, the consumption of information, of the articles published at Nutrición Hospitalaria present parameters similar to other journals on health science. However, good data on obsolescence are observed, which reveal the good validity of most of the references studied.

Impactia: automating the study of the scientific production

Introduction The Andalusian Public Health System Virtual Library (Biblioteca Virtual del Sistema Sanitario Público de Andalucía, BV-SSPA) was set up in June 2006. It consists of a regional government action with the aim of democratizing the health professional access to quality scientific information, regardless of the professional workplace. Andalusia is a region with more than 8 million inhabitants, with 100,000 health professionals for 41 hospitals, 1,500 primary healthcare centres, and 28 centres for non-medical attention purposes (research, management, and educational centres). Objectives The Department of Development, Research and Investigation (R+D+i) of the Andalusian Regional Government has, among its duties, the task of evaluating the hospitals and centres of the Andalusian Public Health System (SSPA) in order to distribute its funding. Among the criteria used is the evaluation of the scientific output, which is measured using bibliometry. It is well-known that the bibliometry has a series of limitations and problems that should be taken into account, especially when it is used for non-information sciences, such us career, funding, etc. A few years ago, the bibliometric reports were done separately in each centre, but without using preset and well-defined criteria, elements which are basic when we need to compare the results of the reports. It was possible to find some hospitals which were including Meeting Abstracts in their figures, while others do not, and the same was happening with Erratum and many other differences. Therefore, the main problem that the Department of R+D+i had to deal with, when they were evaluating the health system, was that bibliometric data was not accurate and reports were not comparable. With the aim of having an unified criteria for the whole system, the Department of R+D+i ordered the BV-SSPA to do the year analysis of the scientific output of the system, using some well defined criteria and indicators, among whichstands out the Impact Factor. Materials and Methods As the Impact Factor is the bibliometric indicator that the virtual library is asked to consider, it is necessary to use the database Web of Science (WoS), since it is its owner and editor. The WoS includes the databases Science Citation Index (SCI), Social Sciences Citation Index (SSCI) and Arts & Humanities Citation Index. To gather all the documents, SCI and SSCI are used; to obtain the Impact Factor and quartils, it is used the Journal Citation Reports, JCR. Unlike other bibliographic databases, such us MEDLINE, the bibliometric database WoS includes the address of all the authors. In order to retrieve all the scientific output of the SSPA, we have done general searches, which are afterwards processed by a tool developed by our library. We have done nine different searches using the field ‘address’; eight of them including ‘Spain’ and each one of the eight Andalusian Regions, and the other one combining ‘Spain’ with all those cities where there are health centres, since we have detected that there are some authors that do not use the region in their signatures. These are some of the search strategies: AD=Malaga and AD=Spain AD=Sevill* and AD=Spain AD=SPAIN AND (AD=GUADIX OR AD=BAZA OR AD=MOTRIL) Further more, the field ‘year’ is used to determine the period. To exploit the data, the BV-SSPA has developed a tool called Impactia. It is a web application which uses a database to store the information of the documents generated by the SSPA. Impactia allows the user to automatically process the retrieved documents, assigning them to their correspondent centres. In order to do the classification of documents automaticaly, it was necessary to detect the huge variability of names of the centres that the authors use in their signatures. Therefore, Impactia knows that if an author signs as “Hospital Universitario Virgen Macarena”, “HVM” or “Hosp. Virgin Macarena”, he belongs to the same centre. The figure attached shows the variability found for the Empresa Publica Hospital de Poniente. Besides the documents from WoS, Impactia includes the documents indexed in Scopus and in other databases, where we do bibliographic searches using similar strategies to the later ones. Aware that in the health centres and hospitals there is a lot of grey literature that is not gathered in databases, Impactia allows the centres to feed the application with these documents, so that all the SSPA scientific output is gathered and organised in a centralized place. The ones responsible of localizing this gray literature are the librarians of each one of the centres. They can also do statements to the documents and indicators that are collected and calculated by Impactia. The bulk upload of documents from WoS and Scopus into Impactia is monthly done. One of the main issues that we found during the development of Impactia was the need of dealing with duplicated documents obtained from different sources. Taking into account that sometimes titles might be written differently, with slashes, comas, and so on, Impactia detects the duplicates using the field ‘DOI’ if it is available or comparing the fields: page start, page end and ISSN. Therefore it is possible to guarantee the absence of duplicates. Results The data gathered in Impactia becomes available to the administrative teams and hospitals managers, through an easy web page that allows them to know at any moment, and with just one click, the detailed information of the scientific output of their hospitals, including useful graphs such as percentage of document types, journals where their scientists usually publish, annual comparatives, bibliometric indicators and so on. They can also compare the different centres of the SSPA. Impactia allows the user to download the data from the application, so that he can work with this information or include them in their centres’ reports. This application saves the health system many working hours. It was previously done manually by forty one librarians, while now it is done by only one person in the BV-SSPA during two days a month. To sum up, the benefits of Impactia are: It has shown its effectiveness in the automatic classification, treatment and analysis of the data. It has become an essential tool for all managers to evaluate quickly and easily the scientific production of their centers. It optimizes the human resources of the SSPA, saving time and money. It is the reference point for the Department of R+D+i to do the scientific health staff evaluation.