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Incidence of multiple sclerosis among European Economic Area populations, 1985-2009: the framework for monitoring

  • Alcalde-Cabero, Enrique
  • Almazan-Isla, Javier
  • García-Merino, Antonio
  • de Sá, Joao
  • Pedro-Cuesta, Jesus de
Background: A debate surrounding multiple sclerosis epidemiology has centred on time-related incidence increases and the need of monitoring. The purpose of this study is to reassess multiple sclerosis incidence in the European Economic Area. Methods: We conducted a systematic review of literature from 1965 onwards and integrated elements of original research, including requested or completed data by surveys authors and specific analyses. Results: The review of 5323 documents yielded ten studies for age- and sex-specific analyses, and 21 studies for time-trend analysis of single data sets. After 1985, the incidence of multiple sclerosis ranged from 1.12 to 6.96 per 100,000 population, was higher in females, tripled with latitude, and doubled with study midpoint year. The north registered increasing trends from the 1960s and 1970s, with a historic drop in the Faroe Islands, and fairly stable data in the period 1980-2000; incidence rose in Italian and French populations in the period 1970-2000, in Evros (Greece) in the 1980s, and in the French West Indies in around 2000. Conclusions: We conclude that the increase in multiple sclerosis incidence is only apparent, and that it is not specific to women. Monitoring of multiple sclerosis incidence might be appropriate for the European Economic Area, Sí
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Spatial distribution of Parkinson's disease mortality in Spain, 1989-1998, as a guide for focused aetiological research or health-care intervention

  • Pedro-Cuesta, Jesus de
  • Rodríguez-Farré, Eduard
  • Lopez-Abente, Gonzalo
Background Aetiologically, genetic and environmental factors having an uneven spatial distribution may underlie Parkinson's disease (PD). Undiagnosis of PD in selected regions might have limited access to treatment with levodopa and simultaneously, if present at death, determined PD underreporting at the death record. The purpose of this study was to describe and analyse municipal mortality due to PD in Spain in aetiological and interventional perspective. Methods PD mortality at a municipal level was modelled using the Besag-York- Molliè autoregressive spatial model, combining demographic information with cause-of-death diagnostic data (International Classification of Diseases 9th Revision (ICD-9) code 332.0). Municipal relative risks (RRs) were independently estimated for women, men and both sexes, and plotted on maps depicting smoothed RR estimates and the distribution of the posterior probability of RR>1. Results A south-north gradient, with large geographical areas suggesting clustered towns with high mortality, was seen in Asturias, the Basque Country, Balearic Islands and, particularly, in the Lower Ebro valley around Tarragona. Similarly, there was a suggestion that lowest mortality was clustered in the south-east and south-west. We identified some isolated or clustered municipalities with high mortality that were situated near industrial plants reported to be associated with environmental xenobiotic emissions. However, the same pattern was also observed for some cities with low mortality. Conclusion Municipal PD mortality in Spain was unevenly distributed. Patterns were roughly similar to reported provincial PD mortality and use of levodopa. While the overall pattern appears to result from spatially selective PD undiagnosis, and can not be ascribed to industrial emissions, it can not be excluded that selected "hot spots" reflect genetic factors and/or environmental exposures inducing parkinsonism. A few municipal populations, located in low-mortality-risk areas in the vicinity of polluting plants or registering high excess PD mortality, might constitute a priority for conducting direct etiological studies. Additionally, interventions aimed to reduce potential PD undiagnosis might be most appropriate in the South, The study was supported by the Spanish Consortia for Biomedical Research in Neurodegenerative Diseases (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas - CIBERNED) and Epidemiology & Public Health (Centro de Investigación Biomédica sobre Epidemiología y Salud Pública - CIBERESP), and by Grant No. EPY-1176/02 from the Carlos III Institute of Health (Instituto de Salud Carlos III - ISCIII)., Sí
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Physical disease in schizophrenia: a population-based analysis in Spain

  • Bouza, Carmen
  • Lopez-Cuadrado, Teresa
  • Amate, Jose Maria
Background: Physical disease remains a challenge in patients with schizophrenia. Our objective was to determine the epidemiological characteristics and burden of physical disease in hospitalized patients with schizophrenia. Methods: We analyzed the 2004 Spanish National Hospital Discharge Registry, identified records coded for schizophrenia (295.xx) and characterized the physical diseases using the ICD-9 system and the Charlson Index. We also calculated standardized mortality ratios (SMRs) versus the general population adjusted by age and calendar time. Results: A total of 16, 776 cases (mean age: 43 years, 65% males) were considered for analysis. Overall, 61% of cases had at least one ICD-9 physical code and 32% had more than one ICD-9 code. The Charlson index indicated that 20% of cases had a physical disease of known clinical impact and prognostic significance. Physical disease appeared early in life (50% of cases were 15-31 years of age) and increased rapidly in incidence with age. Thus, for patients aged 53 years or more, 84% had at least one physical ICD-9 code. Apart from substance abuse and addiction, the most prevalent diseases were endocrine (16%), circulatory (15%), respiratory (15%), injury-poisoning (11%), and digestive (10%). There were gender-related differences in disease burden and type of disease. In-hospital mortality significantly correlated with age, the Charlson Index and several ICD-9 groups of physical disease. Physical disease was associated with an overall 3.6-fold increase in SMRs compared with the general population. Conclusions: This study provides the first nationally representative estimate of the prevalence and characteristics of physical disease in hospitalized patients with schizophrenia in Spain. Our results indicate that schizophrenia is associated with a substantial burden of physical comorbidities; that these comorbidities appear early in life; and that they have a substantial impact on mortality. This information raises concerns about the consequences and causes of physical disorders in patients with schizophrenia. Additionally, it will help to guide the design and implementation of preventive and therapeutic programs from the viewpoint of clinical care and in terms of healthcare service planning., Funding for this study was provided by the Spanish R&D Grant no. PI06/90571. The funding body had no further role in study design, data collection, analysis, interpretation, writing of the report, or the decision to submit the paper for publication, Sí
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Development and validation of the competence in evidence based practice questionnaire (EBP-COQ) among nursing students

  • Ruzafa-Martinez, Maria
  • Lopez-Iborra, Lidon
  • Moreno-Casbas, Teresa
  • Madrigal-Torres, Manuel
Background: Nursing educators need rigorously developed instruments to assess competency in evidence based practice (EBP) at undergraduate level. This concept is defined as the capability to choose and use an integrated combination of knowledge, skills and attitudes with the intention to develop a task in a certain context. Also, we understand that EBP is gaining knowledge and skills, as well as increasing positive attitudes toward EBP that will promote a change in behaviour to implement EBP in practice. This study aims to develop a psychometric test of the Evidence Based Practice Evaluation Competence Questionnaire (EBP-COQ) among undergraduate nursing students. Methods: The questionnaire was developed by item generation through a review of scientific literature and focus groups. The instrument was validated in terms of content validity through an expert review. The EBP-COQ was administered to a cohort of nursing students (n =100) to evaluate test reliability and select the best items. Psychometric properties of the final instrument were assessed in a sample of 261 nursing students. Results: The EBP-COQ consisted of 25 items. A factorial analysis grouped the items into the three categories that define competence relating to EBP: attitude, knowledge and skills. Cronbach’s alpha was 0.888 for the entire questionnaire. The factor solution explained 55.55% of the variance. Conclusions: EBP-COQ appears to measure with adequate reliability the attributes of undergraduate nursing students’ competence in EBP. The instrument is quick to disseminate and easy to score, making it a suitable instrument for nursing educators to evaluate students’ self-perceived competence in EBP., This work has been supported by a grant from FIS (Fondo de Investigación Sanitaria, Grant PI060913)., Sí
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Factors associated with the utilization of primary care emergency centers in a Spanish region with high population dispersion: a mixed-methods study

  • Sanz-Barbero, Belén
  • Otero Garcia, Laura
  • Blasco-Hernandez, Teresa
  • San Sebastián, Miguel
BACKGROUND: Adequate access to primary care emergency centers is particularly important in rural areas isolated from urban centers. However, variability in utilization of emergency services located in primary care centers among inhabitants of nearby geographical areas is understudied. The objectives of this study are twofold: 1) to analyze the association between the availability of municipal emergency care centers and utilization of primary care emergency centers (PCEC), in a Spanish region with high population dispersion; and 2) to determine healthcare providers' perceptions regarding PCEC utilization. METHODS: A mixed-methods study was conducted. Quantitative phase: multilevel logistic regression modeling using merged data from the 2003 Regional Health Survey of Castile and Leon and the 2001 census data (Spain). Qualitative phase:14 in-depth- interviews of rural-based PCEC providers. RESULTS: Having PCEC as the only emergency center in the municipality was directly associated with its utilization (p < 0.001). Healthcare providers perceived that distance to hospital increased PCEC utilization, and distance to PCEC decrease its use. PCEC users were considered to be predominantly workers and students with scheduling conflicts with rural primary care opening hours. CONCLUSIONS: The location of emergency care centers is associated with PCEC utilization. Increasing access to primary care by extending hours may be an important step toward optimal PCEC utilization. Further research would determine whether lower PCEC use by certain groups is associated with disparities in access to care., This study is funded by National Health Funding Research. Project IP 080306 and by the Umeå Centre for Global Health Research, funded by FAS, the Swedish Council for Working Life and Social Research (Grant no. 2006–1512)., Sí
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Economic benefits of methylmercury exposure control in Europe: Monetary value of neurotoxicity prevention

  • Bellanger, Martine
  • Pichery, Céline
  • Aerts, Dominique
  • Berglund, Marika
  • Castaño, Argelia
  • Čejchanová, Mája
  • Crettaz, Pierre
  • Davidson, Fred
  • Esteban, Marta
  • Fischer, Marc E
  • Gurzau, Anca Elena
  • Halzlova, Katarina
  • Katsonouri, Andromachi
  • Knudsen, Lisbeth E
  • Kolossa-Gehring, Marike
  • Koppen, Gudrun
  • Ligocka, Danuta
  • Miklavčič, Ana
  • Reis, M. Fátima
  • Rudnai, Peter
  • Tratnik, Janja Snoj
  • Weihe, Pál
  • Budtz-Jørgensen, Esben
  • Grandjean, Philippe
Background: Due to global mercury pollution and the adverse health effects of prenatal exposure to methylmercury (MeHg), an assessment of the economic benefits of prevented developmental neurotoxicity is necessary for any cost-benefit analysis. Methods: Distributions of hair-Hg concentrations among women of reproductive age were obtained from the DEMOCOPHES project (1,875 subjects in 17 countries) and literature data (6,820 subjects from 8 countries). The exposures were assumed to comply with log-normal distributions. Neurotoxicity effects were estimated from a linear dose-response function with a slope of 0.465 Intelligence Quotient (IQ) point reduction per μg/g increase in the maternal hair-Hg concentration during pregnancy, assuming no deficits below a hair-Hg limit of 0.58 μg/g thought to be safe. A logarithmic IQ response was used in sensitivity analyses. The estimated IQ benefit cost was based on lifetime income, adjusted for purchasing power parity. Results: The hair-mercury concentrations were the highest in Southern Europe and lowest in Eastern Europe. The results suggest that, within the EU, more than 1.8 million children are born every year with MeHg exposures above the limit of 0.58 μg/g, and about 200,000 births exceed a higher limit of 2.5 μg/g proposed by the World Health Organization (WHO). The total annual benefits of exposure prevention within the EU were estimated at more than 600,000 IQ points per year, corresponding to a total economic benefit between €8,000 million and €9,000 million per year. About four-fold higher values were obtained when using the logarithmic response function, while adjustment for productivity resulted in slightly lower total benefits. These calculations do not include the less tangible advantages of protecting brain development against neurotoxicity or any other adverse effects. Conclusions: These estimates document that efforts to combat mercury pollution and to reduce MeHg exposures will have very substantial economic benefits in Europe, mainly in southern countries. Some data may not be entirely representative, some countries were not covered, and anticipated changes in mercury pollution all suggest a need for extended biomonitoring of human MeHg exposure., Sí
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Development and validation of a questionnaire on 'Satisfaction with dermatological treatment of hand eczema' (DermaSat)

  • Ruiz, Miguel A
  • Heras, Felipe
  • Alomar, Agusti
  • Conde-Salazar, Luis
  • de la Cuadra, Jesús
  • Serra, Esther
  • Regalado, Francisco
  • Halbach, Ralf
  • GEIDAC Group (Grupo Español para la Investigación de la Dermatitis de Contacto y Alergia Cutánea)
OBJECTIVE: To develop a self-administered short questionnaire to assess patient satisfaction with medical treatment for hand eczema (dermatitis) with good psychometric properties. METHOD: The content of the questionnaire was determined on the basis of clinical consultation with groups of patients, from studying the existing instruments, and from discussions with a panel of seven experts. A first draft version containing 38 items organised in six dimensions was tested on a pilot sample of patients to assess its legibility. The extended version was then tested on a sample of 217 patients of both genders enrolled at 18 hospitals representative of the national distribution. The questionnaire was supplied together with the Morisky-Green compliance questionnaire, the health-related quality of life (HRQL) SF-12 questionnaire, and a visual analogue scale (VAS) of perceived health status to assess concurrent validity. The dimensionality was reduced by means of exploratory factor analysis, and reliability was evaluated on the basis of internal consistency and two halves reliability estimates. Item discriminant capability and questionnaire discriminant validity with respect to known groups of patients (by gender, principal diagnosis, age, disease severity and treatment) were also assessed. RESULTS: The reduction and validation sample was composed of 54% women and 46% men, of various educational levels with an average age of 43 years (SD = 13.7). Of those who responded, 26% were diagnosed with hyperkeratotic dermatitis of the palms and 27% of the fingertips, and 47% with recurring palmar dyshidrotic eczema. The questionnaire was shortened to a version containing 17 items grouped in six dimensions: effectiveness, convenience, impact on HRQL, medical follow-up, side effects, and general opinion. Cronbach's alpha coefficient reached a value of 0.9. The dimensions showed different degrees of correlation, and the scores had a normal distribution with an average of 58.4 points (SD = 18.01). Treatment satisfaction scores attained correlations between 0.003 and 0.222 with the HRQL measures, and showed higher correlations with the effectiveness (r = 0.41) and tolerability (0.22) measures, but very low correlation with compliance (r = 0.015). Significant differences were observed between some diagnoses and treatments. CONCLUSIONS: The shortened questionnaire proved to have good psychometric properties, providing excellent reliability, satisfactorily reproducing the proposed structure and supplying evidence of validity., Sí
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Infectivity to Phlebotomus perniciosus of dogs naturally parasitized with Leishmania infantum after different treatments

  • Miró, Guadalupe
  • Gálvez, Rosa
  • Fraile, Cristeta
  • Descalzo, Miguel Angel
  • Molina, Ricardo
BACKGROUND: In Europe most dogs with clinical leishmaniosis are treated with leishmanicides, typically antimonials combined with allopurinol and good clinical recovery is observed in a high number of these dogs. Through xenodiagnosis, the capacity of a treated animal to infect the vector of the disease under treatment is assessed as a measure of the chemotherapeutic efficacy of the drug used. The objective of the present study was to evaluate through direct xenodiagnosis the infectivity to Phlebotomus perniciosus of dogs naturally parasitized with Leishmania infantum after treatment, and to follow the clinical and parasite course of disease. Thirty two dogs with clinical leishmaniosis were assigned to one of three treatment groups: meglumine antimoniate plus allopurinol (Group A), meglumine antimoniate (Group B) or allopurinol (Group C). During the study, the dogs were examined before treatment (Day 0) and bimonthly thereafter until Day 180 (six months post-treatment onset). RESULTS: The three groups were scored over time according to the effects of treatment on clinical signs and clinical-pathological variables. Significant differences in clinical scores were observed between Group A and the other two groups, indicating the combined treatment was the most effective. After treatment, bone marrow cultures were positive for the parasite in 30.8% of dogs in some of the check ups (3 or 25% in Group A, 1 or 11.1% in Group B, and 4 or 80% in Group C). Our xenodiagnosis experiments revealed that 15.4% of treated dogs were still able to infect sand flies at some point after treatment (2 dogs or 16.6% in Group A, 2 or 22.2% in Group B and none in Group C). Only 7.7% of the entire study population could infect sand flies as from the second month post-treatment onset. CONCLUSION: The three treatment regimens tested significantly reduced the infectivity of dogs towards sand flies, thus diminishing the epidemiological risks of treated dogs both for human beings and other healthy dogs. Despite its low cure rate, the use of allopurinol after a course of leishmanicide treatment is proposed to keep dogs non-infectious during the disease transmission season (4-6 months in southern Europe)., The authors are indebted to the owners of all the dogs participating in this study. Publication of the CVBD6 thematic series was sponsored by Bayer Animal Health GmbH., Sí
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Sequence analysis of the 3’-untranslated region of HSP70 (type I) genes in the genus Leishmania: its usefulness as a molecular marker for species identification

  • Requena, Jose M
  • Chicharro, Carmen
  • García, Lineth
  • Parrado, Rudy
  • Puerta, Concepción J
  • Cañavate, Carmen
BACKGROUND: The Leishmaniases are a group of clinically diverse diseases caused by parasites of the genus Leishmania. To distinguish between species is crucial for correct diagnosis and prognosis as well as for treatment decisions. Recently, sequencing of the HSP70 coding region has been applied in phylogenetic studies and for identifying of Leishmania species with excellent results. METHODS: In the present study, we analyzed the 3'-untranslated region (UTR) of Leishmania HSP70-type I gene from 24 strains representing eleven Leishmania species in the belief that this non-coding region would have a better discriminatory capacity for species typing than coding regions. RESULTS: It was observed that there was a remarkable degree of sequence conservation in this region, even between species of the subgenus Leishmania and Viannia. In addition, the presence of many microsatellites was a common feature of the 3'-UTR of HSP70-I genes in the Leishmania genus. Finally, we constructed dendrograms based on global sequence alignments of the analyzed Leishmania species and strains, the results indicated that this particular region of HSP70 genes might be useful for species (or species complex) typing, improving for particular species the discrimination capacity of phylogenetic trees based on HSP70 coding sequences. Given the large size variation of the analyzed region between the Leishmania and Viannia subgenera, direct visualization of the PCR amplification product would allow discrimination between subgenera, and a HaeIII-PCR-RFLP analysis might be used for differentiating some species within each subgenera. CONCLUSIONS: Sequence and phylogenetic analyses indicated that this region, which is readily amplified using a single pair of primers from both Old and New World Leishmania species, might be useful as a molecular marker for species discrimination., This work was supported by grants from the Ministerio de Ciencia y Tecnología (BFU2009-08986), the Fondo de Investigaciones Sanitarias (ISCIII-RETIC RD06/0021/0008-FEDER and ISCIII-RETIC RD06/0021/0009-FEDER), and Agencia Española de Cooperación Internacional para el Desarrollo (AECID, A/024740/09). Also, an institutional grant from Fundación Ramón Areces is acknowledged., Sí
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Detection of a new insect flavivirus and isolation of Aedes flavivirus in Northern Italy

  • Roiz, David
  • Vazquez, Ana
  • Rosso, Fausta
  • Arnoldi, Daniele
  • Girardi, Matteo
  • Cuevas, Laureano
  • Perez-Pastrana, Esperanza
  • Sanchez-Seco, Paz
  • Tenorio, Antonio
  • Rizzoli, Annapaola
BACKGROUND: During recent years, numerous novel 'insect flaviviruses' have been discovered in natural mosquito populations. In a previous study we described the presence of flavivirus DNA sequences integrated in Aedes albopictus (Asian tiger mosquito) populations from Northern Italy in 2007. METHODS: During 2008 we collected and tested Aedes females for flavivirus presence and developed phylogenetic analysis, virus isolation, electron microscopy studies and RNAse treatments. RESULTS: We detected a high prevalence of flavivirus in Ae. albopictus (77.5%). The phylogenetic analysis identified the insect flavivirus sequences as Aedes flavivirus (AEFV) recently described in Japan, and that may have been introduced in Italy travelling with the tiger mosquito. Some of these pools grew in C6/36 cells, producing cytopathic effects, and the RNase treatment results showed the presence of the detected sequences in RNA forms. Furthermore, we detected a new insect flavivirus in one pool of Aedes cinereus/geminus mosquitoes. Phylogenetic analysis of this virus shows that it forms a distinct cluster within the clade of insect flavivirus. CONCLUSIONS: This is the first study to report a high prevalence, to describe the seasonal activity and an isolation of the insect flavivirus Aedes flavivirus in Europe. Moreover we describe the detection of a new insect flavivirus detected from Ae. cinereus mosquitoes from Italy. These flavivirus may be common, ubiquitous and diverse in nature and we discuss the implications of the insect flavivirus group in virus evolution and transmission., This work was supported by The Autonomous Province of Trento, postdoctoral project Risktiger, “Risk assessment of new arbovirus diseases transmitted by Aedes albopictus (Diptera: Culicidae) in the Autonomous Province of Trento” and EuroWestNile EU grant HEALTH.2010.2.3.3-3 Project 261391., Sí
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