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Immuno-proteomic screening has identified several tumor-associated autoantibodies (AAb) that may have diagnostic capacity for invasive epithelial ovarian cancer, with AAbs to P53 proteins and cancer-testis antigens (CTAGs) as prominent examples. However, the early detection potential of these AAbs has been insufficiently explored in prospective studies. We performed ELISA measurements of AAbs to CTAG1A, CTAG2, P53 and NUDT11 proteins, for 194 patients with ovarian cancer and 705 matched controls from the European EPIC cohort, using serum samples collected up to 36 months prior to diagnosis under usual care. CA125 was measured using electrochemo-luminiscence. Diagnostic discrimination statistics were calculated by strata of lead-time between blood collection and diagnosis. With lead times ≤6 months, ovarian cancer detection sensitivity at 0.98 specificity (SE98) varied from 0.19 [95% CI 0.08-0.40] for CTAG1A, CTAG2 and NUDT1 to 0.23 [0.10-0.44] for P53 (0.33 [0.11-0.68] for high-grade serous tumors). However, at longer lead-times, the ability of these AAb markers to distinguish future ovarian cancer cases from controls declined rapidly; at lead times >1 year, SE98 estimates were close to zero (all invasive cases, range: 0.01-0.11). Compared to CA125 alone, combined logistic regression scores of AAbs and CA125 did not improve detection sensitivity at equal level of specificity. The added value of these selected AAbs as markers for ovarian cancer beyond CA125 for early detection is therefore limited.

[Background & Aims] Liver fibrosis is the main determinant of long-term outcome in chronic liver diseases. Little is known about the prevalence of liver fibrosis in the general population. The aim of the study was to investigate the prevalence of liver fibrosis in the general adult population with unknown liver disease., [Methods] This was a population-based, cross-sectional study performed in the Barcelona metropolitan area. Subjects aged 18 to 75 years old were identified randomly from citizens included in the primary health care registry. Of 4866 subjects invited, 3076 participated (63.2%). Liver fibrosis was estimated by measuring liver stiffness (LS) with transient elastography (TE). Liver histology was assessed in 92 subjects with increased LS., [Results] Prevalence estimates of increased LS (≥6.8, ≥8.0, and ≥9.0 kPa) were 9.0%, 5.8%, and 3.6%, respectively. The etiology of liver disease was mainly nonalcoholic fatty liver disease (NAFLD), followed by alcohol risk consumption (consumption of ≥21 standard drinking units/wk in men and ≥14 standard drinking units/wk in women). Factors independently associated with increased LS were male sex, abdominal obesity, type 2 diabetes, serum glucose, high-density lipoprotein, and triglyceride levels. Subjects without risk factors for NAFLD or without alcohol risk consumption had a very low prevalence of increased LS. The best cut-off value of LS for significant liver fibrosis (F2–F4) was 9.2 kPa, with high sensitivity and specificity. TE was more accurate than alanine aminotransferase, NAFLD fibrosis score, or Fibrosis 4. An algorithm for screening for liver fibrosis using TE in the community setting is proposed., [Conclusions] These findings show a high prevalence of silent liver disease with advanced fibrosis mainly related to NAFLD in adult European subjects without known liver disease. An LS value less than 9.2 kPa predicts the absence of significant liver fibrosis with high accuracy and could be used for screening purposes., The project received a research grant from the Carlos III Institute of Health, Ministry of Economy and Competitiveness (Spain), awarded on the 2011 call under the Health Strategy Action 2013–2016, within the National Research Program oriented to Societal Challenges, within the Technical, Scientific and Innovation Research National Plan 2013–2016, with reference PI11/0267, co-funded by European Union European Regional Development Fund funds. Also supported by grants from Fondo de Investigación Sanitaria Instituto de Salud Carlos III-Subdirección General de Evaluación and the European Regional Development Fund Fondo Europeo de Desarrollo Regional (PI16/ 00043), the Agencia de Gestió d’Ajuts Universitarisi de Recerca, and the European Horizon 20/20 program, H20/20-SC1-2016-RTD, and an Institució Catalana de Recerca I Estudis Avançats Academy Award (P.G.).

Intake of dairy products has been associated with risk of some cancers, but findings are often inconsistent and information on hepatocellular carcinoma (HCC) risk is limited, particularly from prospective settings. The aim of our study was to investigate the association between consumption of total and specific dairy products (milk/cheese/yogurt) and their components (calcium/vitamin D/fats/protein), with first incident HCC (N(cases) = 191) in the European Prospective Investigation into Cancer and Nutrition cohort, including a nested case-control subset (N(cases) = 122) with the assessment of hepatitis B virus/hepatitis C virus infections status, liver damage and circulating insulin-like growth factor (IGF)-I levels. For cohort analyses, multivariable-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI). For nested case-control analyses, conditional logistic regression was used to calculate odds ratios and 95% CI. A total of 477,206 participants were followed-up for an average of 11 years (person-years follow-up = 5,415,385). In the cohort study, a significant positive HCC risk association was observed for total dairy products (highest vs. lowest tertile, HR = 1.66, 95% CI: 1.13-2.43; p(trend) = 0.012), milk (HR = 1.51, 95% CI: 1.02-2.24; p(trend) = 0.049), and cheese (HR = 1.56, 95% CI: 1.02-2.38; p(trend) = 0.101), but not yogurt (HR = 0.94, 95% CI: 0.65-1.35). Dietary calcium, vitamin D, fat and protein from dairy sources were associated with increased HCC risk, whereas the same nutrients from nondairy sources showed inverse or null associations. In the nested case-control study, similar results were observed among hepatitis-free individuals. Results from this large prospective cohort study suggest that higher consumption of dairy products, particularly milk and cheese, may be associated with increased HCC risk. Validation of these findings in other populations is necessary. Potential biologic mechanisms require further exploration.

Fundamentos: Las desigualdades de género en salud han sido amplia- mente documentadas. El principal objetivo es evaluar si existen diferencias de género en salud percibida y utilización de servicios sanitarios, y su relación con la doble carga de trabajo, en una muestra representativa de población inmigrante y autóctona de la Región de Murcia (RM). Métodos: Se utilizaron datos de la ENS 2006 y el Estudio Salud y Culturas, 1.303 inmigrantes y 1.303 españoles residentes en la RM. La combinación del trabajo reproductivo y remunerado se consideró “doble carga” (DC). Se estimó la razón de prevalencia (RP) de la percepción positiva de salud, morbilidad crónica, limitación de actividad, visitas al médico, hospitalización, visitas a urgencias y consumo de fármacos, en cada grupo de origen, mediante métodos de regresión. Se construyeron dos modelos, añadiendo el ajuste por DC al modelo ajustado por variables sociodemográficas. Se realizó análisis intere intrasexo. Resultados: Al ajustar por DC no se observaron cambios en las diferencias entre sexos [RP mujeres/hombres de percepción positiva salud: 0,70 (0,54-0,89) europeos Este; 0,87 (0,79-0,95) autóctonos / morbilidad crónica: 1,44 (1,14-1,82) hispanoamericanos; 1,36 (1,19-1,55) autóctonos / limitación actividad: 2,23 (1,29-3,83) hispanoamericanos; 1,45 (1,01-2,10) autóctonos / consulta médico: 1,93 (1,50-2,48) hispanoamericanos; 1,74 (1,06-2,86) marroquíes; 1,32 (1,09-1,59) autóctonos / hospitalización: 1,80 (1,02-3,17) hispanoamericanos], casi los mismos que sin ajustar. Las mujeres consumieron más fármacos que los hombres. Entre sexos, hombres (1,19; 1,06-1,33) y mujeres (1,18; 1,01-1,40) de la RM con DC compartida declararon mayor percepción positiva de salud que aquellos sin DC; hombres hispanoamericanos con DC sin ayuda: 0,67 (0,47-0,94). Conclusiones: Las mujeres presentan peores indicadores de salud y mayor uso de servicios sanitarios independientemente del origen. La doble carga no modifica las desigualdades de género en salud.

Fundamentos: En el año 2009 se unificó el Certificado Médico de Defunción con el Boletín Estadístico de Defunción (CMD/BED). En la estadística nacional del año 2009 se detectó un aumento inusual en las defunciones por diabetes mellitus (DM) y enfermedad hipertensiva (HTA) en relación a la tendencia en años anteriores. El objetivo del trabajo es estudiar las causas documentales del aumento y describir los procedimientos y consecuencias en las tasas tras la revisión y recodificación de ambas causas. Métodos: Se revisaron todas las certificaciones de defunciones de 2009 por DM e HTA en la Región de Murcia (casos=670) según pautas previas de recodificación directa o tras consulta al médico certificador. Se diseñó una encuesta telefónica al médico certificador para determinar la exactitud de la pauta de recodificación. Se calculó el índice Kappa e intervalo de confianza (IC95%) entre las causas iniciales y recodificadas. Se estimó la tasa de confirmación e IC95% tras consulta telefónica; y las tasas totales y específicas por edad del año 1999 a 2009 con y sin corrección para DM e HTA. Resultados: Los casos concordantes fueron el 37% en DM y 29% HTA. El índice Kappa entre causas iniciales y finales fue del 49% (IC95%, 45-54%). Las tasas de confirmación fueron del 47% (IC95%, 43 a 52%) para DM y del 38% (IC95%, 34 a 43%) para HTA. Las tasas iniciales anuales del año 2009 para DM se corrigieron de 21,4 por cien mil habitantes a 17,1, y de 19,0 a 14,0 para HTA. Las respectivas tasas específicas por edad de 70 a 84 y más años presentaron reducciones similares. Conclusiones: La revisión restableció la tendencia temporal de la mortalidad por DM e HTA en 2009, e identificó que no tuvo variaciones respecto a años anteriores. Se detectó que la cumplimentación errónea de DM e HTA provenía del CMD/BED.

Fundamento: el efecto de las temperaturas sobre la mortalidad ha sido estudiado mas en profundidad que el efecto sobre la morbilidad. En Murcia se monitorizan el numero de urgencias diarias y los casos de golpes de calor atendidos en los hospitales de la Region. Objetivo: valorar el efecto de la temperatura sobre el numero de urgencias hospitalarias y la utilidad de estos indicadores para vigilar la morbilidad por calor. Metodos: se ha estudiado el efecto de la temperatura sobre el numero de urgencias en verano (periodo 2000-2005), estimando el incremento porcentual de urgencias cuando se superan los umbrales establecidos por el Ministerio de Sanidad y Consumo (Ta maxima 38oC y Ta minima 22,4oC) y por cada grado de aumento de temperatura, expresado en Riesgo Relativo (RR) con un IC95%. Se han cotejado los golpes de calor comunicados con los ingresos registrados en el Conjunto Minimo Basico de Datos al Alta Hospitalaria (CMBD). Resultados: En 2000-2005 las urgencias se incrementaron un 1,6% en los dias con mas de 22,4oC de minima (RR 1,016; IC95% 1,0076-1,0244), y un 0,21% por cada grado de aumento de la minima (RR 1,0021; IC95% 1,0000-1,0044). El 38% de los golpes de calor ingresados no se notificaron, y el 40% de los notificados tenian exposicion laboral. Conclusiones: La temperatura minima podria tener un mayor efecto en Murcia que la maxima. Con los actuales umbrales, el numero de urgencias diarias no parece un indicador adecuado para monitorizar el efecto de la temperatura, necesitandose informacion sobre el diagnostico y la edad. Los golpes de calor aportan informacion parcial del impacto, pero resaltan grupos de poblacion en riesgo menos considerados.

Contains fulltext : 51396.pdf (Publisher’s version ) (Closed access) Vitamin C is an antioxidant and inhibitor of carcinogenic N-nitroso compound production in the stomach. Higher dietary vitamin C consumption is associated with decreased risk of gastric cancer (GC) in numerous case-control studies, but data from prospective studies are limited, particularly so for blood measures of vitamin C. The objective of this study was to determine the association of plasma and dietary vitamin C levels with the risk of GC in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 European countries. Using a fluorometric method, vitamin C was measured in pre-diagnostic plasma from 215 GC cases (matched controls = 416). Conditional logistic regression models adjusted by body mass index, total energy intake, smoking status/duration/intensity and Helicobacter pylori infection status were used to estimate relative cancer risks. No association with GC risk was observed for dietary vitamin C, whereas an inverse GC risk was observed in the highest versus lowest quartile of plasma vitamin C [odds ratio (OR) = 0.55, 95% confidence interval (CI) = 0.31-0.97, P(trend) = 0.043], which was maintained after exclusion of cases with

OBJECTIVES: To investigate the role of factors that modulate the association between alcohol and mortality, and to provide estimates of absolute risk of death.DESIGN: The European Prospective Investigation into Cancer and nutrition (EPIC).SETTING: 23 centres in 10 countries.PARTICIPANTS: 380 395 men and women, free of cancer, diabetes, heart attack or stroke at enrolment, followed up for 12.6 years on average.MAIN OUTCOME MEASURES: 20 453 fatal events, of which 2053 alcohol-related cancers (ARC, including cancers of upper aerodigestive tract, liver, colorectal and female breast), 4187 cardiovascular diseases/coronary heart disease (CVD/CHD), 856 violent deaths and injuries. Lifetime alcohol use was assessed at recruitment.RESULTS: HRs comparing extreme drinkers (≥30 g/day in women and ≥60 g/day in men) to moderate drinkers (0.1-4.9 g/day) were 1.27 (95% CI 1.13 to 1.43) in women and 1.53 (1.39 to 1.68) in men. Strong associations were observed for ARC mortality, in men particularly, and for violent deaths and injuries, in men only. No associations were observed for CVD/CHD mortality among drinkers, whereby HRs were higher in never compared to moderate drinkers. Overall mortality seemed to be more strongly related to beer than wine use, particularly in men. The 10-year risks of overall death for women aged 60 years, drinking more than 30 g/day was 5% and 7%, for never and current smokers, respectively. Corresponding figures in men consuming more than 60 g/day were 11% and 18%, in never and current smokers, respectively. In competing risks analyses, mortality due to CVD/CHD was more pronounced than ARC in men, while CVD/CHD and ARC mortality were of similar magnitude in women.CONCLUSIONS: In this large European cohort, alcohol use was positively associated with overall mortality, ARC and violent death and injuries, but marginally to CVD/CHD. Absolute risks of death observed in EPIC suggest that alcohol is an important determinant of total mortality.

An increase in the incidence of group C meningococcal disease was observed in the Murcia Region (Spain) during 1996–1997. In September 1997, a massive vaccination campaign was implemented among the population aged 18 months to 19 years. The aim of this study was to assess the seroconversion rate of children aged 18–59 months and the persistence of immune response 1 year after vaccination. A total of 296 children were included. Blood samples were obtained before vaccination and 1 month and 1 year after vaccination. Three point seven percent of the children had bactericidal antibody titres of ≥1:8 before vaccination. One month after vaccination seroconversion was 63.7%, with a growing trend related to age at vaccination (p

Tras el estudio de la situacion de la enfermedad meningococica durante la temporada 1996-19971, la revision de toda la documentacion disponible sobre la vacuna frente al meningococo serogrupo C, consultados distintos expertos en el tema y sometido a discusion en la Comision Asesora de Inmunizaciones, en Julio de 1997 la Consejeria de Sanidad decide la vacunacion de la poblacion de mayor riesgo, comprendida por individuos entre 18 meses y 19 anos de edad, ademas de los mayores de 18 meses con inmunodeficiencias, asplenia funcional o anatomica y, con deficit de complemento en su parte terminal o en la via alternativa. Con esta intervencion se pretende disminuir la morbimortalidad debida a la infeccion por el meningococo serogrupo C. La campana de vacunacion se desarrollara entre el 1 de septiembre y el 31 de octubre de 1997. En los menores de 5 anos de edad, segun la documentacion disponible, no solo la eficacia vacunal es inferior que en edades posteriores sino que la duracion de la inmunidad es mas corta; algunos autores senalan que la duracion es de 2 o 3 anos e incluso puede ser inferior a un ano. La revacunacion, tras la primera dosis vacunal, no muestra un efecto "booster" pero si pueden alcanzarse niveles de anticuerpos semejantes a los de primera dosis vacunal. Por este motivo y coincidiendo con la campana de vacunacion, se propone realizar un estudio para conocer la seroconversion vacunal y la titulacion de anticuerpos al ano de la vacunacion en un grupo de ninos mayores de 18 meses y menores de 5 anos de edad. Esta informacion seria un valioso instrumento que ayudaria a decidir en un futuro, en base a la situacion epidemiologica, si deben revacunarse o no los ninos menores de 5 anos de edad.

Background: Attention to patients with acute minor-illnesses requesting same-day consultation represents a major burden in primary care. The workload is assumed by general practitioners in many countries. A number of reports suggest that care to these patients may be provided, at in least in part, by nurses. However, there is scarce information with respect to the applicability of a program of nurse management for adult patients with acute minor-illnesses in large areas. The aim of this study is to assess the effectiveness of a program of nurse algorithm-guided care for adult patients with acute minor illnesses requesting same-day consultation in primary care in a largely populated area. Methods: A cross-sectional study of all adult patients seeking same day consultation for 16 common acute minor illnesses in a large geographical area with 284 primary care practices. Patients were included in a program of nurse case management using management algorithms. The main outcome measure was case resolution, defined as completion of the algorithm by the nurse without need of referral of the patient to the general practitioner. The secondary outcome measure was return to consultation, defined as requirement of new consultation for the same reason as the first one, in primary care within a 7-day period. Results: During a two year period (April 2009-April 2011), a total of 1,209,669 consultations were performed in the program. Case resolution was achieved by nurses in 62.5% of consultations. The remaining cases were referred to a general practitioner. Resolution rates ranged from 94.2% in patients with burns to 42% in patients with upper respiratory symptoms. None of the 16 minor illnesses had a resolution rate below 40%. Return to consultation during a 7-day period was low, only 4.6%. Conclusions: A program of algorithms-guided care is effective for nurse case management of patients requesting same day consultation for minor illnesses in primary care.

Gender inequalities in health have been largely documented. The main objective of this study is to assess whether there are gender differences in perceived health and health services utilization, and their relation with double workload in a representative sample of immigrants and Murcian natives.We used data from the NHS 2006 and Health and Culture Study, 1,303 immigrants and 1,303 Spanish, both residents in the Region of Murcia. With the combination of reproductive work and paid work we built up the variable 'double workload' (DW). We estimated the prevalence ratio (PR) for positive self-perceived health, chronic morbidity, activity limitation, doctor's visits, hospitalization, emergency and drug use, by origin, using regression methods. Two models were constructed by adding double burden to the basic model adjusted by sociodemographic variables. Analyses were performed between and within sex.After adjusting for DW, no changes were seen in the differences by gender [RP women/men of positive perception health: 0.70 (0.54-0.89) East European; 0.87 (0.79-0.95) autochthonous / chronic morbidity: 1.44 (1.14-1.82) Hispanic; 1.36 (1.19-1.55) autochthonous / activity limitation: 2.23 (1.29-3.83) Hispanic; 1.45 (1.01-2.10) autochthonous / doctor's visits: 1.93 (1.50-2.48) Hispanic; 1.74 (1.06-2.86) Moroccan; 1.32 (1.09-1.59) autochthonous / hospitalization: 1.80 (1.02-3.17) Hispanic], almost the same than unadjusted. Women used more drugs than men. Within sexes, both autochthonous men (1.19; 1.06-1.33) and women (1.18; 1.01-1.40) with shared DW had more positive self-perceived health than those without DW. Hispanic men with DW without assistance: 0.67 (0.47-0.94).Women have worse health indicators and greater use of health services regardless of origin. Consideration of the double workload does not explain gender inequalities in health.

ResumenEl objetivo de este estudio es validar un cuestionario de frecuencias para poder clasificar individuos según su actividad física reciente (AF) (últimas dos semanas), aplicable a ambos sexos. Se recogieron siete diarios de AF a 30 hombres y 32 mujeres durante dos semanas. Entonces se cumplimentó el cuestionario de frecuencias cubriendo el mismo período de tiempo. Las kilocalorías medias de gasto energético obtenidas mediante el cuestionario fueron superiores a las calculadas a partir de los diarios en ambos sexos. Las diferencias (prueba t para datos apareados) entre las medias obtenidas con ambos métodos fueron significativas en las mujeres y en algunos subgrupos de actividades para ambos sexos. El coeficiente de correlación de Pearson entre ambos métodos fue de 0,78 en hombres y de 0,65 en mujeres. El grado de concordancia entre métodos clasificando a los sujetos según terciles de AF total fue menor en los hombres (Kappa ponderado Kw=0,35, p

The Medical Death Certificate and the Death Statistics Bulletin were unified and implemented in the year 2009 in Spain. National statistics detected an unusual increase for diabetes mellitus (DM) and hypertensive disease (HT) deaths in 2009, in relation to previous years trend.The objective is to study the documental causes of the increase, and describe the procedures and consequences in rates, after the revision and recodification of DM and HT.All death certificates in 2009 for diabetes and hypertension in the Region of Murcia (cases=670) were revised, according to previous guidelines for direct recoding after consultation to the certifying physician. A telephone survey to certifying physician was designed to determine the accuracy of the pattern of recoding. Kappa index and 95% confidence intervals (95%CI) were performed between initial and recoded causes. Confirmation rate and 95%CI was estimated after phone inquiry to the certifying physician, and the annual age-adjusted and age-specific rates from 1999 to 2009 (uncorrected and corrected) for DM and HT were calculated.Simple agreement was 37% for DM and 30% for HT. The Kappa index between the initial and final causes was 49% (95%CI, 45 to 54%). Confirmation rates were 47% (95%CI, 43 to 52%) for DM and 38% (95%CI, 34 to 43%) for HT. The initial annual rates of 2009 for DM were corrected from 21.4 per 100,000 inhabitants to 17.1, and from 19.0 to 14.0 for hypertension. The respective specific age rates of 70 to 84 and older experienced similar reductions.The revision restored temporal trends in mortality of DM and HT in 2009, and identified no variations from previous years. It was detected that the erroneous fulfillment of DM AND HT came from the new death certificate.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is unknown in Spain. The purpose of detecting NAFLD patients is to determine the associated factors and prevent its evolution to more severe forms. The aim of this study is to determine the prevalence and factors associated with NAFLD.This is a multicentre, cross-sectional, populational study. Individuals between 15 and 85 years of age were randomly selected from 25 primary healthcare centres in the province of Barcelona, Spain. Clinical histories were reviewed, and anamnesis, physical examination, blood analysis and hepatic echography were performed. Individuals with an alcohol intake greater than 30 g/day in men and greater than 20 g/day in women or with known liver disease were excluded.Seven hundred and sixty-six individuals with a mean age of 53+/-14 years (range 17-83, 42.2% men) were included in the study. One hundred and ninety-eight individuals presented NAFLD with echographic criteria (prevalence 25.8, 33.4% men and 20.3% women P0.001). On multivariate analysis, the following were associated with NAFLD: male sex [odds ratio (OR): 2.34, 95% confidence interval (95% CI): 1.57-3.49], age (OR: 1.04 per year, 95% CI: 1.02-1.05), metabolic syndrome (OR: 2.19, 95% CI: 1.29-3.72), insulin resistance (OR: 6.00, 95% CI: 3.43-10.5) and alanine aminotransferase (OR: 4.21, 95% CI: 2.23-7.95). Of the individuals who consumed alcohol, 29.4% consumed alcohol within the inclusion criteria, with a mean of 9.17+/-6.75 standard beverage units per week. Moderate alcohol intake was not related to NAFLD, although a possible protector effect was found with the quantity consumed among the drinkers who did not consume excessive amounts of alcohol (OR: 0.93 per standard beverage units, 95% CI: 0.88-0.98).NAFLD prevalence in our population is very high. Male sex, age, metabolic syndrome, insulin resistance and alanine aminotransferase are the factors associated with NAFLD. Furthermore, studies should be carried out with respect to the controversial effect of alcohol on NAFLD.

Background Non alcoholic fatty liver disease (NAFL) consists in the accumulation of fat vacuoles in the cytoplasm of hepatocytes. Many etiologic factors are associated with NAFL, such as, the metabolic syndrome factors, medications, bariatric surgery, nutritional disorders. However, very little information is available on the clinical relevance of this disorder as a health problem in the general population. Methods and design The aim of the study is establish the risk factors most frequently associated with NAFL in a general adult population assigned to the primary care units and to investigate the relationship between each component of the metabolic syndrome and the risk of having a NAFL. A population based case-control, observational and multicenter study will be carried out in 18 primary care units from the "Area de Gestión del Barcelonés Nord y Maresme" (Barcelona) attending a population of 360,000 inhabitants and will include 326 cases and 370 controls. Cases are defined as all subjects fulfilling the inclusion criteria and with evidence of fatty liver in an abdominal ultrasonography performed for any reason. One control will be randomly selected for each case from the population, matched for age, gender and primary care center. Controls with fatty liver or other liver diseases will be excluded. All cases and controls will be asked about previous hepatic diseases, consumption of alcohol, smoking and drugs, and a physical examination, biochemical analyses including liver function tests, the different components of the metabolic syndrome and the HAIR score will also be performed. Paired controls will also undergo an abdominal ultrasonography. Discussion This study will attempt to determine the factors most frequently associated with the presence of NAFL investigate the relationship between the metabolic syndrome and the risk of fatty liver and study the influence of the different primary care professionals in avoiding the evolution of the disease.

The effect of the weather temperature on mortality has been studied more in depth than its effect on morbidity. In Murcia, the number of daily emergencies and the cases of heat stroke for which care is provided at the hospitals in this Region have been studied.to evaluate the effect that the weather temperature has on the number of hospital emergencies and the use of these indicators for the surveillance of hot weather-related morbidity.The effect of the weather temperature on the number of summertime emergencies (2000-2005) has been studied by estimating the percentage increase in emergencies when the weather temperature thresholds established by the Ministry of Health and Consumer Affairs (Max. 38 degrees C and Min. 22.4 degrees C) are exceeded, and by each degree of temperature rise. Results have been stated as Relative Risk (RR) with a 95% CI. A comparison has been drawn between the heat strokes notified and the hospital admissions recorded in the Minimum Basic Data Set at Hospital Discharge (MBDS).Within the 2000-2005 period, the number of emergencies rose by 1.6% on those days when the minimum temperature for the day was above 22.4 degrees C (RR: 1.016; 95% CI 1.0076-1.0244) and by 0.21% for each degree of rise in the minimum temperature for the day (RR: 1.0021, 95% CI 1.0000-1.0044). A total of 38% of the heat strokes admitted to hospital were not reported, of which 40% had occupational exposure.The minimum temperature for the day could have a greater effect in Murcia than the maximum for the day. Based on the current thresholds, the number of emergencies/day does not seem to be a suitable indicator for monitoring the effect of the weather temperature, information on the diagnosis and the age being needed. Heat strokes provide partial information on the impact, but highlight less-considered population groups at risk.

Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. E-Cadherin is an adhesion molecule that is thought to be involved in GC. Germline mutations in the E-Cadherin gene (CDH1) have been identified in hereditary diffuse GC. Also, a promoter polymorphism at position -160 C/A has been suggested to lead to transcriptional down regulation and has been shown to affect GC risk in some studies. However, very little information exists on the GC risk association of other CDH1 polymorphisms and it is unclear whether any associations may be different by GC anatomical sites or histological types. Thus, a case-control study (cases = 245/controls = 950) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort was conducted to assess the GC risk association of eight CDH1 gene polymorphisms. None of the CDH1 polymorphisms or haplotypes analysed were associated with GC risk and no differences of effect were observed by Helicobacter pylori infection status. However, three CDH1 polymorphisms in the same haplotype block, including the CDH1-160C/A, interacted with smoking to increase GC risk in smokers but not in never smokers. These findings should be confirmed in larger independent studies. © 2008 Elsevier Ltd. All rights reserved.

A highly sensitive and specific one-step multiplex RT-PCR assay has been developed and standardised for the simultaneous and differential detection of the most important vesicular viruses affecting livestock foot-and-mouth disease virus (FMDV), swine vesicular disease virus (SVDV), and vesicular stomatitis virus (VSV). The method uses three primer sets, each one specific for the corresponding virus, selected to detect of all serotypes of FMD and VS. The detection range was confirmed by examination of a collection of 31 isolates of the three target viruses. The specificity of the assay was also demonstrated by testing other related viruses, uninfected cell line cultures and healthy pig tissues. The testing of blood and serum samples from animals infected experimentally proved that the method can be useful for early diagnosis of the diseases, even before the first vesicular lesions are visualized in the infected pigs. An assessment of the performance of the multiplex RT-PCR was carried out using a panel of more than 100 samples from animals infected experimentally, showing the suitability of the method for a rapid (less than 6 h), sensitive and specific differential diagnosis in clinical samples. Additionally, a uniplex RT-PCR for VSV, that amplifies the two viral serotypes, was also developed and tested as a rapid tool for the diagnosis of this vesicular disease. © 2007 Elsevier B.V. All rights reserved.

International audience; EPIC-Heart is the cardiovascular component of the European Prospective Investigation into Cancer and Nutrition (EPIC), a multi-centre prospective cohort study investigating the relationship between nutrition and major chronic disease outcomes. Its objective is to advance understanding about the separate and combined influences of lifestyle (especially dietary), environmental, metabolic and genetic factors in the development of cardiovascular diseases by making best possible use of the unusually informative database and biological samples in EPIC. Between 1992 and 2000, 519,978 participants (366,521 women and 153,457 men, mostly aged 35-70 years) in 23 centres in 10 European countries commenced follow-up for cause- specific mortality, cancer incidence and major cardiovascular morbidity. Dietary information was collected with quantitative questionnaires or semi-quantitative food frequency questionnaires, including a 24-h dietary recall sub-study to help calibrate the dietary measurements. Information was collected on physical activity, tobacco smoking, alcohol consumption, occupational history, socio-economic status, and history of previous illnesses. Anthropometric measurements and blood pressure recordings were made in the majority of participants. Blood samples were taken from 385,747 individuals, from which plasma, serum, red cells, and buffy coat fractions were separated and aliquoted for long-term storage. By 2004, an estimated 10,000 incident fatal and non-fatal coronary and stroke events had been recorded. The first cycle of EPIC-Heart analyses will assess associations of coronary mortality with several prominent dietary hypotheses and with established cardiovascular risk factors. Subsequent analyses will extend this approach to non-fatal cardiovascular outcomes and to further dietary, biochemical and genetic factors.

To validate the ability of a hospital administration data set (minimum data set [MDS]) to detect incident cases of colorectal cancer using the Murcia Cancer Registry (MCR) as the gold standard and to measure agreement between the MDS and registration of colorectal cancer.A cross sectional validation study of the MDS of the main hospital in the region of Murcia (Spain) was conducted. The study population consisted of incident cases of colorectal cancer in 2000 obtained from the MCR and cases in the MDS of the above-mentioned hospital for the same year with an ICD-9 diagnostic code between 153.0 and 154.1, eliminating readmissions. During the process, two analyses were performed: one analysis with the principal diagnosis only and another with all the diagnostic codes. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and agreement was calculated with their 95% confidence intervals (CI).With the first diagnosis only, the MDS detected 80% of the incident cases of colorectal cancer with a PPV of 75%. With all the diagnoses, the MDS detected 85% of the cases with a PPV of 64%. The agreement in codification was high at three digits (kappa 88% [95% CI, 0.79-0.97] first diagnosis, 89% [95% CI, 0.80-0.97] all diagnoses) as well as at four digits (kappa 77% [IC, 0.68-0.85] first diagnosis, 78% [95% CI, 0.70-0.86] all diagnoses) in both analyses.Because of its high sensitivity, the MDS is a good source for detecting incident cases of cancer. The high agreement found in the site of colorectal cancer helps to consolidate the MDS as a data source for cancer registration.

Fundamento: Diversos países han realizado estudios de comparabilidad entre las revisiones 10ª y 9ª de la Clasificación Internacional de Enfermedades para listas agregadas de causas de muerte. En España el proyecto COMPARA pretende evaluar el impacto del cambio de revisión. Métodos: Estudio epidemiológico transversal descriptivo de 88.048 defunciones inscritas en 1999 en España con la causa de muerte doblemente codificada en CIE-9 y 10. Se establecen las correspondencias teóricas entre CIE en las listas INE y Murcia. Se calculan las razones de comparabilidad e intervalos de confianza y el índice kappa global. Resultados: Descienden las enfermedades infecciosas (-1,7%), las hepatitis víricas (-12,3%), mientras que aumenta el Sida (5,7%). Las neoplasias aumentan el 0,3% por la incorporación del síndrome mielodisplásico (55,2%). Se incrementa la diabetes mellitus (2,1%). Se reducen los trastornos mentales al salir las demencias hacia la enfermedad de Alzheimer (28,6%). Las enfermedades cardiovasculares descienden ligeramente (-1,4%), sin impacto sobre las cerebrovasculares, aunque el infarto agudo de miocardio decrece (-0,6%) con aumento de la enfermedad isquémica cardiaca (0,3%). La neumonía decrece (-12,5%) y la cirrosis hepática se aumenta (4,3%). Las entidades mal definidas aumentan por la cesión de las insuficiencias cardiorrespiratorias. Las causas externas no varían sin que recojan la precisión de la CIE-9. La lista INE - 102 grupos obtiene un índice kappa del 95,4%, similar a las variantes de Murcia. Conclusiones: Aunque el impacto global de la CIE-10 es menor, se deberían tener en cuenta las razones de comparabilidad significativas de los grupos de causas de muerte con diferencias absolutas importantes entre las revisiones.

The development and standardisation of a novel, highly sensitive and specific one-step hot start multiplex RT-PCR assay is presented for the simultaneous and differential diagnosis of African swine fever (ASF) and Classical swine fever (CSF). The method uses two primer sets, each one specific for the corresponding virus, amplifying DNA fragments different in length, allowing a gel-based differential detection of the PCR products. Universal detection of ASF and CSF virus strains was achieved through selection of primers in conserved viral genome regions. The detection range was confirmed by analysis of a large collection of isolates of the two viruses. The high specificity of the assay was proven by testing related viruses, uninfected cell line cultures and healthy pig tissues. Additional confirmatory tests of the ASF and CSF virus amplicon specificity, based on restriction endonuclease analysis with BsmA I or Ban II, respectively, are also described. The analysis of whole blood and serum samples from experimentally infected animals proved the usefulness of the method for an early diagnosis of both diseases, even before the appearance of the first clinical signs. A study of 150 positive field samples from several ASF and CSF outbreaks showed the suitability of this method for a rapid (less than five hours), sensitive and specific differential diagnosis in clinical samples. In addition, a highly sensitive and specific uniplex RT-PCR for CSFV was also developed and standardised as a powerful tool for fast and early diagnosis of the disease. © INRA, EDP Sciences, 2004.

Here, we report the development and further characterisation of a novel PrP-specific monoclonal antibody 2A11. By Western blot analysis, 2A11 reacts with PrPC from a variety of species including cow, sheep, pig, hamster, rabbit, cat, dog, deer and mouse but fails to react with human, chicken and turtle PrP. Reactivity to PrPC in Western blot was found to be dependent on the redox state of the protein since binding of mAb 2A11 to its epitope was more effective in reducing conditions. 2A11 binding site was mapped within a region comprised by residues 171-179 (six octarepeats bovine PrP notation; 163-171 for the ovine PrP notation). Interestingly, in immunohistochemistry (IHC) analysis, immunoreactivity was greatly enhanced after proteinase K (PK) sample treatment, while little or no reaction was observed in non-PK-treated BSE samples and samples from healthy animals. Quantitative differences in reactivity to BSE prions after PK treatment were also observed, to a lesser extent, by Western blot analysis. Since definitive diagnosis of prion diseases rely on IHC assays of proteinase K-treated samples, the use of mAb 2A11 might contribute to reduce the occurrence of false positive detection due to incomplete proteinase K digestion. © 2003 Elsevier Ireland Ltd and The Japan Neuroscience Society. All rights reserved.

African horse sickness (AHS) is a disease of equids, characterized by severe pulmonary oedema and caused by an orbivirus. To determine the role of pulmonary intravascular macrophages (PIMs) in the development of pulmonary microvascular changes in this disease, five horses were given an intravenous inoculation of 106TCID50of serotype 4 of AHS virus. Viral replication was detected in endothelial cells, PIMs, interstitial macrophages and fibroblasts. Alveolar and interstitial oedema, and changes in pulmonary microvasculature, consisting mainly of the sequestration of neutrophils and the formation of platelet aggregates and fibrinous microthrombi, were related to endothelial changes and to a high degree of PIM activation. This suggested that the PIMs, once activated, contributed to these vascular changes by releasing chemical inflammatory mediators.

African horse sickness (AHS) was induced in five horses by inoculation, to determine the ultrastructural changes in endothelial cells of capillaries in the myocardium, lung, spleen and liver. The animals developed cardiac and mixed forms of the disease. Alterations detected in the endothelial cells of the vessels of infected animals included: the presence of structures associated with viral infection, hypertrophy, degenerative changes, appearance of cytoplasmic projections, changes in permeability, alteration of intercellular junctions, loss of endothelium, subendothelial deposition of cell debris and fibrin, and vascular repair. In association with these changes, oedema, haemorrhages and microthromboses were detected, particularly in the myocardium and lung. This study showed that infection of, and changes to, the capillary endothelial cells of the organs under study was independent of the form in which the disease manifested itself but was dependent on the organ and blood vessel type. Thus, different levels of viral tropism were observed for the endothelial cells of the vessels in different organs. Viral infection was commonest in the endothelial cells of myocardial vessels, followed by those in the lung, whereas in the spleen and liver, endothelial cell infection was rare and, in the case of the liver, limited to the interstitial capillaries.

Twelve pigs were inoculated with a highly virulent strain of hog cholera virus (HCV) to study viral infection of megakaryocytes in the bone marrow and spleen. Immunohistochemical and ultrastructural examination revealed HCV infection in a small proportion (2.5-9.0%) of these cells from the 2nd to the 9th day after inoculation, at which time the experiment was terminated. Megakaryocyte infection accounts for the presence of viral antigens in platelets. The latter may represent a passive vehicle for spreading the virus in the animal.

FUNDAMENTO: Ampliar las experiencias de evaluacion del aprendizaje y de la satisfaccion, en los talleres de pre y postgrado de medicina para la mejora en la certificacion de las causa de defuncion, con las aportaciones de la Region de Murcia, desde 1992 a 1996. METODOS: Con un diseno epidemiologico cuasi-experimental del tipo pretest-postest, se imparte un taller teorico-practico de 2 horas, a estudiantes de medicina, MIR en formacion de Medicina Familiar y Comunitaria, y medicos generales en curso de obtener dicha especialidad. El taller pretende ensenar la utilidad de las estadisticas de mortalidad y las normas internacionales de certificacion de la OMS. Al principio y al final se evalua la formacion mediante un supuesto. Se elaboran indicadores de calidad formal, concepto, y resultado en la cumplimentacion. Tambien se administra un cuestionario de satisfaccion. RESULTADOS: En cinco anos se imparten 23 talleres a 646 asistentes, y se incluyen 472 pares de ejercicios y 586 encuestas de satisfaccion. En el pretest, mas del 78% de los indicadores individuales son correctos y el 52,3% de los participantes los realizan todos bien. Existen mejoras estadisticamente significativas en los grupos de indicadores de concepto y resultado, pero no en la forma, que parte de una alta calificacion (77,5%). El 24,6% de los estudiantes mejora la asignacion de la causa de defuncion frente al 14,4% de los medicos. Segun los participantes, el contenido del curso es muy-adecuado/adecuado (92,7%), sin diferencias entre los tipos de asistentes, y equilibrado en teoria y practica (64,7%). El 81,3% de los medicos y el 80,2% de los estudiantes afirman que es util para certificar correctamente una defuncion, independientemente de la formacion previa. CONCLUSIONES: Las buenas calificaciones iniciales son superadas tras la intervencion educativa. De acuerdo con la eficacia demostrada en los talleres para la mejora de la certificacion de las causas de defuncion, se propone su generalizacion y el analisis de su impacto en las estadisticas de mortalidad.

FUNDAMENTO: La Región de Murcia es un área de alta mortalidad coronaria y cerebrovascular en el contexto español. Además, la tendencia en mortalidad coronaria, descendente en pr��cticamente todas las áreas geográficas españolas, se ha incrementado en ésta ligeramente durante el periodo 1985-1991. En este estudio se evalúan las prevalencias poblacionales de diferentes factores de riesgo cardiovascular en la Región de Murcia. MÉTODOS: El trabajo se ha realizado mediante una encuesta a una población muestral representativa de la población adulta de la región (18-65 años), en la que se obtuvo una tasa de respuesta del 61%. Se realizó medición estandarizada de la tensión arterial, de la obesidad y de los lípidos séricos, junto a la aplicación de un cuestionario sobre consumo de tabaco, actividad física y diabetes. Presentación de datos estandarizados globales y truncados para los grupos de edad de 35-64 años. La recogida de información se llevó a cabo desde noviembre de 1991 a marzo de 1993. RESULTADOS: La prevalencia de consumo de tabaco resultante es de 54,4% en hombres y 31,3% en mujeres. Las cifras de hipertensión son superiores en los hombres (32,3% prevalencia, 16,4% tratamiento, 2,6% control del total de hipertensos y 15,6% control entre sólo los hipertensos tratados) que en las mujeres (23,7%, 34,3%, 9,5% y 27,8%, respectivamente). Las cifras medias de colesterol son bajas en ambos sexos así como altas las cifras de HDL-colesterol en todos los grupos de edad. El Índice de Masa Corporal medio es 26,7 en ambos sexos, aunque las mujeres presentan una mayor variabilidad. La prevalencia de diabetes declarada se sitúa alrededor del 3-4%. CONCLUSIONES: Comparadas estas cifras, para los grupos de edad correspondientes, con las proporcionadas por el estudio MONICA y otros estudios en población adulta española se observa que, salvo el elevado consumo de tabaco y el alto índice de obesidad, la prevalencia de factores de riesgo cardiovascular observada en la Región de Murcia estarían en el extremo más bajo de la distribución de centros MONICA. Es posible, por tanto, que existan diferencias en la asistencia al paciente coronario que expliquen en parte las tendencias desfavorables en mortalidad coronaria observadas en la Región de Murcia.

African horsesickness virus serotype 4 (AHSV-4) outer capsid protein VP2, or VP2 and VP5 plus inner capsid protein VP7, derived from single or dual recombinant baculovirus expression vectors were used in different combinations to immunize horses. When the proteins were purified by affinity chromatography, the combination of all three proteins induced low levels of neutralizing antibodies and conferred protection against virulent virus challenge. However, purified VP2 or VP2 and VP5 in the absence of VP7 failed to induce neutralizing antibodies and protection. Immunization with non-purified proteins enhanced the titres of neutralizing antibodies. Again, the combination of the three proteins was able to confer total protection to immunized horses, which showed absence of viraemia. The antigenicity of recombinant VP2 was analysed with a collection of 30 MAbs. Both purified and unpurified recombinant VP2 proteins showed different antigenic patterns in comparison to that of VP2 on virions. An immunization experiment with four more horses confirmed these results. The vaccine described here would not only prevent the disease, but would drastically reduce the propagation of the virus by vectors.

ResumenSe plantea conocer el consumo anual de rifampicina y su tendencia, para estimar la prevalencia de enlermos de tuberculosis en tratamiento de la Comunidad Autónoma de Murcia. Para ello se calcula la tasa truncada por edad correspondiente a la población de 12 años y más a partir del consumo de rifampicina en comprimidos, por extrapolación se calcula la tasa de consumidores por 100.000 habitantes para la población total. Esta tasa es de 46,75 ± 7,89 (DE) para los años 1984–86 y su tendencia, desde el año 1984, es descendente. Se comenta el interés de comparar este indicador con los obtenidos a partir del Riesgo Anual de Infección (RAI) y, si se encontrara que sus tendencias son equiparables, sus ventajas por la facilidad y rapidez de obtención.SummaryTo estimate the prevalence of tuberculosis patients in treatment in the Autonomous Community of Murcia, a study of the annual consumption of rifampicine and its tendency was made. The rate for the population standardised by age for those aged 12 or over was calculated from the consumption of rifampin tablets, and by extrapolation, the rate of consumers per 100.000 inhabitants for the total population. This was 46,75 ± 7,89 (SD) for the years 1984–1986, which has been decreasing since 1984. The interest in comparing this indicator with those obtained from the Annual Risk of Infection (ARI), whether its tendencies are found to be comparable, and its advantages in terms of ease of collection are commented upon.

ResumenEn este trabajo se revisan los usos del certificado de defunción en los registros de cáncer de base poblacional, así como los principales problemas y limitaciones que se plantean.Los usos más importantes son la identificación de casos, el seguimiento pasivo y la elaboración de algunos indicadores para el control de calidad. Entre los problemas se destacan los relativos a la accesibilidad a los certificados y la repercusión del registro de casos, cuya única fuente es el certificado de defunción, en la exactitud de las tasas de incidencia.SummaryIn this study we review the uses of the certificate of health in population-based cancer registries, as well as their main problems and limitations.The most important uses are: case identification, passive follow-up and the elaboration of some quality control indicators. Among the problems, the most important ones are those related with the access to the certificate and the impact of deathcertificate-only cases on the calculation of incidence rates.

Background The value of abdominal echography in primary care is great because it is innocuous, inexpensive, easy to perform and provides a great deal of information making this the first examination to be requested in cases of probable abdominal disease. However, too many abdominal echographies are probably requested overcrowding the Departments of Radiodiagnosis with not always justified petitions or with repetition of tests based on little clinical criteria. Methods/Design The aim of the study is to evaluate the adequacy and quality of abdominal echographies requested by primary care physicians in the Maresme County (North of Barcelona), develop guidelines for indicating echographies and reevaluate this adequacy after implementing these guidelines. We will perform a two-phase study: the first descriptive, and retrospective evaluating the adequacy and quality of petitions for abdominal echographies, and in the second phase we will evaluate the impact of recommendations for indicating abdominal echographies for PC physicians on the adequacy and quality of echography petitions thereafter. This study will be carried out in 10 primary care centres in the Maresme (Barcelona). 1067 abdominal echographies requested by primary care physicians from the above mentioned centres from January 2007 to April 2010 and referred to the Department of Radiology and the same number of applications after the intervention. All the petitions for abdominal echographies requested will be analysed and the clinical histories will be obtained to determine demographic variables, the reason for the visit and for the echography petition and diagnostic orientation, clinical and echographic data, evaluation of the echographies according to the quality and variables characterising the professionals requesting the echographies including: age, sex, laboral situation, length of time in work post, formation, etc. To achieve a consensus of the adequacy of abdominal echography, a work group including gastroenterologists, radiologists and general practitioners will be created following the nominal group. This will allow the design of guidelines for the indication of abdominal echography and posterior evaluation of their impact among physicians by diffusion and posterior reevaluation of the adequacy of the petitions.

Fifteen horses were experimentally infected with African horse sickness virus (AHSV) serotype 4. To learn more about the time course of production and specificity of AHSV-specific antibodies, sera were analyzed by immunoblot analysis. Only animals that survived for more than 9 days were able to develop a humoral immune response detectable by immunoblotting. The earliest serological markers corresponded mainly to VP5, VP6, and NS2 and to a lesser extent to VP3, NS1, and NS3. Neutralizing antibodies to VP2 were not detected by immunoblotting, suggesting that they are mostly conformation dependent. VP7-specific antibodies were detected later in infection. These results make NS2 and VP6 the most attractive candidates for the rapid diagnosis of the infection.

La demencia constituye una prioridad en Salud Pública y, al no disponer de tratamiento curativo, es necesario identificar factores que permitan implementar medidas preventivas. La Dieta Mediterránea (DM) ha demostrado beneficios sobre la salud, pero su papel en la prevención de la demencia no ha sido bien establecido. Por ello, el objetivo de esta Tesis Doctoral fue evaluar la incidencia de demencia en la cohorte de demencia del Estudio Prospectivo Europeo Sobre Cáncer y Nutrición (EPIC) en España y analizar su relación con la adhesión a un patrón de DM. EPIC es una cohorte con más de 500.000 participantes de 10 países europeos diseñada para evaluar la influencia de la dieta y otros factores de estilo de vida en la aparición del cáncer y otras patologías crónicas. La cohorte de demencia de EPIC-España consta de 25.015 participantes de tres regiones españolas (Guipúzcoa, Navarra y Murcia) reclutados entre 1992 y 1996, quienes han sido seguidos durante más de 20 años. Para realizar el trabajo actual, se diseñó un protocolo de identificación de casos incidentes de demencia basado en la revisión de historias clínicas. Tras identificar los casos incidentes, se calcularon tasas de incidencia brutas y ajustadas por edad, según sexo y subtipo de demencia (enfermedad de Alzheimer, EA, y no alzhéimer, no-EA). Además, se realizaron estimaciones puntuales de incidencia acumulada por sexo y edad, así como un análisis multivariante para identificar los determinantes independientes asociados a la demencia. Por último, se analizó la relación entre la adhesión a un patrón de DM y el riesgo de demencia. Se recogió información mediante una historia de dieta validada para evaluar la adhesión a la escala relativa de DM (rMED (‘relative Mediterranean diet score’). Se estimaron las hazard ratios (HR) de demencia por niveles del rMED mediante modelos de Cox y se evaluaron los efectos dependientes del tiempo mediante modelos de Royston-Parmar. Las tasas de incidencia globales fueron mayores en mujeres para demencia y EA y similares por sexo para no-EA, y oscilaron desde 0,09 (intervalo de confianza del 95% (IC95%):0,06-0,13) casos de demencia y 0,05 (0,03-0,09) de EA por 1.000 personas-año en menores de 60 años, a 23,2 (15,9-33,8) casos de demencia y 14,6 (9,1-33,5) de EA por 1.000 personas-año en aquellos de 85 o más años. Además, el 12,5% de mujeres y el 9,1% de los hombres con edades al reclutamiento entre 60-65 años desarrollaron demencia tras 20 años. Los principales predictores del riesgo de demencia fueron el bajo nivel educativo, la diabetes y la hiperlipidemia; el alcohol mostró una asociación inversa. En el análisis de la relación entre la DM y el riesgo de demencia, se observó una reducción del riesgo de demencia del 20% (HR=0,80; IC95%:0,60-1,06) entre los participantes con adhesión alta frente a baja al rMED y un 8% de reducción del riesgo de demencia por cada incremento de 2 puntos del rMED (HR=0,92; 0,85-0,99; p=0,021). Por subtipos, se evidenció una asociación inversa entre la adhesión a la DM y el riesgo de demencia no-EA en mujeres (HR2-puntos=0,74; IC95%:0,62-0,89) y de EA en hombres (HR2-puntos=0,88; 0,76-1,01). Esta asociación fue mayor en participantes con bajo nivel educativo. En conclusión, la validación de casos incidentes de demencia mediante historias clínicas en la cohorte de demencia de EPIC-España fue factible. La incidencia de demencia aumentó con la edad y fue mayor en mujeres. El riesgo de demencia fue mayor en personas con bajo nivel educativo, no consumidoras de alcohol y con factores de riesgo cardiovascular. Además, la DM presentó una asociación inversa con la incidencia de demencia, pero la fuerza de la asociación varió por subtipo, sexo y nivel educativo. Dementia constitutes a Public Health priority. As no curative treatment has been developed yet it is necessary to identify potential protective factors that would allow us to establish preventive measures. In this way, following a Mediterranean Diet (MD) has shown beneficial effects on health. However, the potential protective role of MD over dementia has not been well elucidated yet. Thus, the main aim of this Doctoral Thesis was to assess the risk of dementia in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain Dementia cohort and to evaluate the relationship between adherence to a MD pattern and the subsequent risk of dementia. EPIC is a prospective cohort study with over half a million participants from ten European countries, designed to study the association of dietary and lifestyle factors with the risk of cancer and other chronic diseases. The EPIC-Spain Dementia cohort consists of 25,015 participants from three Spanish centers (Gipuzkoa, Navarra, and Murcia), recruited between 1992 and 1996 and followed up for over 20 years. In the present work, a two-step validation protocol based on medical records was designed to ascertain incident cases of dementia in the cohort. After identifying incident cases of dementia, an analysis was carried out to provide incidence rates of dementia. Crude and age-adjusted rates of dementia and sub-types (Alzheimer’s disease, AD, and non-Alzheimer’s disease, non-AD) were calculated by sex. Furthermore, point estimates of the cumulative risk of dementia were obtained by sex and age groups. Additionally, the independent associations of the selected variables with the risk of dementia were assessed. Finally, the relationship between the adherence to a MD pattern and the risk of dementia was evaluated. Data on habitual diet was collected through a validated diet history method to assess adherence to the relative Mediterranean Diet score (rMED). Hazard ratios (HR) of dementia by rMED levels were estimated using multivariable Cox models while time-dependent effects were evaluated using flexible parametric Royston-Parmar (RP) models. Global incidence rates were higher in women for dementia and AD and similar by sex for non-AD. Incidence rates ranged from 0.09 cases of dementia (95% confidence interval (CI):0.06-0.13) and 0.05 (0.03-0.09) of AD per 1000 person-years) in participants below 60 years, to 23.2 (15.9-33.8) cases of dementia and 14.6 (9.1-33.5) of AD (per 1000 person-years) in those ≥85 years. Additionally, up to 12.5% of women and 9.1% of men 60-65 years-old developed dementia within 20 years. Low education, diabetes, and hyperlipidemia were the main independent predictors of dementia risk, whereas alcohol showed an inverse association. The analysis of the relationship between adherence to a MD pattern and the risk of dementia showed that high versus low adherence to the categorical rMED score was associated with a 20% (HR=0.80, 95%CI: 0.60-1.06) lower risk of dementia overall and HR of dementia was 8% (HR=0.92, 0.85-0.99, p=0.021) lower for each 2-point increment of the continuous rMED score. By sub-types, a favorable association was also found in women for non-AD (HR2-points=0.74, 95%CI: 0.62-0.89), while not statistically significant in men for AD (HR2-points=0.88, 0.76-1.01). This association was stronger in participants with lower education. In conclusion, ascertainment of incident dementia in the EPIC-Spain Dementia Cohort study was feasible using information from medical records. Dementia incidence increased with age and was higher among women. Furthermore, dementia risk was higher among subjects with lower education, not drinking alcohol, and presenting cardiovascular risk factors. Finally, adherence to a MD pattern was inversely associated with dementia incidence. The results differed by dementia sub-type, sex, and education but there was no significant evidence of effect modification