Publications by authors named "Carmen Navarro"

348 Publications

Development and validation of a laboratory-based risk score to predict the occurrence of critical illness in hospitalized patients with COVID-19.

Scand J Clin Lab Invest 2021 07 11;81(4):282-289. Epub 2021 May 11.

Laboratory Medicine Department, Virgen Macarena University Hospital, Seville, Spain.

Background: Early identification of patients with COVID-19 who may develop critical illness is of great importance.

Methods: In this study a retrospective cohort of 264 COVID-19 cases admitted at Macarena University was used for development and internal validation of a risk score to predict the occurrence of critical illness in hospitalized patients with COVID-19. Backward stepwise logistic regression was used to derive the model, including clinical and laboratory variables predictive of critical illness. Internal validation of the final model used bootstrapped samples and the model scoring derived from the coefficients. External validation was performed in a cohort of 154 cases admitted at Valme and Virgen del Rocio University Hospital.

Results: A total of 62 (23.5%) patients developed a critical illness during their hospitalization stay, 21 (8.0%) patients needed invasive ventilation, 34 (12.9%) were admitted at the ICU and the overall mortality was of 14.8% (39 cases). 5 variables were included in the final model: age >59.5 years (OR: 3.11;95%CI 1.39-6.97), abnormal CRP results (OR: 5.76;95%CI 2.32-14.30), abnormal lymphocytes count (OR: 3.252;95%CI 1.56-6.77), abnormal CK results (OR: 3.38;95%CI 1.59-7.20) and abnormal creatinine (OR: 3.30;95%CI 1.42-7.68). The AUC of this model was 0.850 with sensitivity of 65% and specificity of 87% and the IDI and NRI were 0.1744 and 0.2785, respectively. The validation indicated a good discrimination for the external population.

Conclusions: Biomarkers add prognostic information in COVID-19 patients. Our risk-score provides an easy to use tool to identify patients who are likely to develop critical illness during their hospital stay.
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http://dx.doi.org/10.1080/00365513.2020.1847313DOI Listing
July 2021

Mediterranean Diet and Risk of Dementia and Alzheimer's Disease in the EPIC-Spain Dementia Cohort Study.

Nutrients 2021 Feb 22;13(2). Epub 2021 Feb 22.

Murcia Biomedical Research Institute (IMIB-Arrixaca), 30120 Murcia, Spain.

The Mediterranean diet (MD) has shown to reduce the occurrence of several chronic diseases. To evaluate its potential protective role on dementia incidence we studied 16,160 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain Dementia Cohort study recruited between 1992-1996 and followed up for a mean (±SD) of 21.6 (±3.4) years. A total of 459 incident cases of dementia were ascertained through expert revision of medical records. Data on habitual diet was collected through a validated diet history method to assess adherence to the relative Mediterranean Diet (rMED) score. Hazard ratios (HR) of dementia by rMED levels (low, medium and high adherence levels: ≤6, 7-10 and ≥11 points, respectively) were estimated using multivariable Cox models, whereas time-dependent effects were evaluated using flexible parametric Royston-Parmar (RP) models. Results of the fully adjusted model 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, = 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 (HR per 2-points = 0.74, 95%CI: 0.62-0.89), while not statistically significant in men for AD (HR per 2-points = 0.88, 0.76-1.01). The association was stronger in participants with lower education. In conclusion, in this large prospective cohort study MD was inversely associated with dementia incidence after accounting for major cardiovascular risk factors. The results differed by dementia sub-type, sex, and education but there was no significant evidence of effect modification.
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http://dx.doi.org/10.3390/nu13020700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927039PMC
February 2021

Development and validation of a prediction model for 30-day mortality in hospitalised patients with COVID-19: the COVID-19 SEIMC score.

Thorax 2021 Feb 25. Epub 2021 Feb 25.

Infectious Diseases Unit, Internal Medicine Service, Hospital Universitario La Paz, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, Spain.

Objective: To develop and validate a prediction model of mortality in patients with COVID-19 attending hospital emergency rooms.

Design: Multivariable prognostic prediction model.

Setting: 127 Spanish hospitals.

Participants: Derivation (DC) and external validation (VC) cohorts were obtained from multicentre and single-centre databases, including 4035 and 2126 patients with confirmed COVID-19, respectively.

Interventions: Prognostic variables were identified using multivariable logistic regression.

Main Outcome Measures: 30-day mortality.

Results: Patients' characteristics in the DC and VC were median age 70 and 61 years, male sex 61.0% and 47.9%, median time from onset of symptoms to admission 5 and 8 days, and 30-day mortality 26.6% and 15.5%, respectively. Age, low age-adjusted saturation of oxygen, neutrophil-to-lymphocyte ratio, estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, dyspnoea and sex were the strongest predictors of mortality. Calibration and discrimination were satisfactory with an area under the receiver operating characteristic curve with a 95% CI for prediction of 30-day mortality of 0.822 (0.806-0.837) in the DC and 0.845 (0.819-0.870) in the VC. A simplified score system ranging from 0 to 30 to predict 30-day mortality was also developed. The risk was considered to be low with 0-2 points (0%-2.1%), moderate with 3-5 (4.7%-6.3%), high with 6-8 (10.6%-19.5%) and very high with 9-30 (27.7%-100%).

Conclusions: A simple prediction score, based on readily available clinical and laboratory data, provides a useful tool to predict 30-day mortality probability with a high degree of accuracy among hospitalised patients with COVID-19.
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http://dx.doi.org/10.1136/thoraxjnl-2020-216001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908055PMC
February 2021

Molecular characterization of invasive serogroup B Neisseria meningitidis isolates from Spain during 2015-2018: Evolution of the vaccine antigen factor H binding protein (FHbp).

J Infect 2021 04 18;82(4):37-44. Epub 2021 Feb 18.

National Reference Laboratory for meningococci, National Centre for Microbiology, Instituto de Salud Carlos III, Ctra, Majadahonda-Pozuelo, Km2., 28220 Majadahonda, Madrid, Spain. Electronic address:

Studies of meningococcal genetic population structure, including the potential associations between surface proteins variants and clonal complexes, are important to understand how new protein MenB vaccines might impact in specific scenarios. With the aim to analyze the diversity of Spanish invasive MenB strains, and genetic variability of the fHbp vaccine antigen, all MenB isolates received at National Reference Laboratory (NRL) from 2015 to 2018 were molecularly characterized.

Material And Methods: 108, 103, 87 and 112 invasive MenB strains isolated during 2015-2018, respectively, were received at NRL. The strains were whole genome sequenced, and porA, fetA, MLST and fHbp variability was analyzed. Potential impact on MenB vaccines coverage was also assessed.

Results: A total of 42, 38 and 3 different FHbp subfamily A, B and A/B hybrid peptides, respectively, were found. FHbp subfamily A peptides were harboured by most of the strains (65.9%), being the most prevalent peptide 45 which was associated with genosubtype 22,14 and cc213. FHbp subfamily B peptides were harboured by 32.4% of the strains, and 6 strains harbouring subfamily A/B hybrid peptides were also found. The 64.15% of the strains showed FHbp variants "exact-match" or "cross-reactive" to the FHbp variants included in rLP2086 vaccine according to hSBA assays in the rLP2086 clinical development, and 15.85% showed FHbp peptides defined as predictors of FHbp-coverage for 4CMenB vaccine by gMATS.

Conclusions: Due to invasive meningococcal strains temporal variability (eg prevalence of the cc213 increased from 3.6% in 2007 to 33% in 2018) affecting to the presence and distribution of the vaccine antigens, continuous detailed meningococcal surveillance and monitoring of the vaccine antigens is needed to determine the degree and durability of coverage provided by these protein vaccine.
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http://dx.doi.org/10.1016/j.jinf.2021.01.030DOI Listing
April 2021

Molecular characterization of invasive serogroup B Neisseria meningitidis isolates from Spain during 2015-2018: Evolution of the vaccine antigen factor H binding protein (FHbp).

J Infect 2021 04 18;82(4):37-44. Epub 2021 Feb 18.

National Reference Laboratory for meningococci, National Centre for Microbiology, Instituto de Salud Carlos III, Ctra, Majadahonda-Pozuelo, Km2., 28220 Majadahonda, Madrid, Spain. Electronic address:

Studies of meningococcal genetic population structure, including the potential associations between surface proteins variants and clonal complexes, are important to understand how new protein MenB vaccines might impact in specific scenarios. With the aim to analyze the diversity of Spanish invasive MenB strains, and genetic variability of the fHbp vaccine antigen, all MenB isolates received at National Reference Laboratory (NRL) from 2015 to 2018 were molecularly characterized.

Material And Methods: 108, 103, 87 and 112 invasive MenB strains isolated during 2015-2018, respectively, were received at NRL. The strains were whole genome sequenced, and porA, fetA, MLST and fHbp variability was analyzed. Potential impact on MenB vaccines coverage was also assessed.

Results: A total of 42, 38 and 3 different FHbp subfamily A, B and A/B hybrid peptides, respectively, were found. FHbp subfamily A peptides were harboured by most of the strains (65.9%), being the most prevalent peptide 45 which was associated with genosubtype 22,14 and cc213. FHbp subfamily B peptides were harboured by 32.4% of the strains, and 6 strains harbouring subfamily A/B hybrid peptides were also found. The 64.15% of the strains showed FHbp variants "exact-match" or "cross-reactive" to the FHbp variants included in rLP2086 vaccine according to hSBA assays in the rLP2086 clinical development, and 15.85% showed FHbp peptides defined as predictors of FHbp-coverage for 4CMenB vaccine by gMATS.

Conclusions: Due to invasive meningococcal strains temporal variability (eg prevalence of the cc213 increased from 3.6% in 2007 to 33% in 2018) affecting to the presence and distribution of the vaccine antigens, continuous detailed meningococcal surveillance and monitoring of the vaccine antigens is needed to determine the degree and durability of coverage provided by these protein vaccine.
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http://dx.doi.org/10.1016/j.jinf.2021.01.030DOI Listing
April 2021

Creation and implementation of a European registry for patients with McArdle disease and other muscle glycogenoses (EUROMAC registry).

Orphanet J Rare Dis 2020 10 15;15(1):187. Epub 2020 Oct 15.

Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, and Research Group on Neuromuscular and Mitochondrial Diseases, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Pg. Vall d'Hebron 119, 08035, Barcelona, Catalonia, Spain.

Background: International patient registries are of particular importance for rare disorders, as they may contribute to overcome the lack of knowledge derived from low number of patients and limited awareness of these diseases, and help to learn more about their geographical or population-based specificities, which is relevant for research purposes and for promoting better standards of care and diagnosis. Our objective was to create and implement a European registry for patients with McArdle disease and other muscle glycogenoses (EUROMAC) and to disseminate the knowledge of these disorders.

Results: Teams from nine different countries (United Kingdom, Spain, Italy, France, Germany, Denmark, Greece, Turkey and USA) created a consortium that developed the first European registry dedicated to rare muscle glycogenoses. A work plan was implemented to design the database and platform that constitute the registry, by choosing clinical, genetics and molecular variables of interest, based on experience gained from previous national registries for similar metabolic disorders. Among dissemination activities, several teaching events were organized in different countries, especially those where the consortium considered the awareness of these diseases needs to be promoted among health professionals and patients.

Conclusion: EUROMAC represents a step forward in the knowledge of those disorders to which it is dedicated, and will have relevant clinical outcomes at the diagnostic, epidemiological, clinical and research level.
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http://dx.doi.org/10.1186/s13023-020-01455-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558742PMC
October 2020

An embryonic stem cell-specific heterochromatin state promotes core histone exchange in the absence of DNA accessibility.

Nat Commun 2020 10 9;11(1):5095. Epub 2020 Oct 9.

Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Tomtebodavägen 23, 17165, Stockholm, Sweden.

Nucleosome turnover concomitant with incorporation of the replication-independent histone variant H3.3 is a hallmark of regulatory regions in the animal genome. Nucleosome turnover is known to be universally linked to DNA accessibility and histone acetylation. In mouse embryonic stem cells, H3.3 is also highly enriched at interstitial heterochromatin, most prominently at intracisternal A-particle endogenous retroviral elements. Interstitial heterochromatin is established over confined domains by the TRIM28-KAP1/SETDB1 corepressor complex and has stereotypical features of repressive chromatin, such as H3K9me3 and recruitment of all HP1 isoforms. Here, we demonstrate that fast histone turnover and H3.3 incorporation is compatible with these hallmarks of heterochromatin. Further, we find that Smarcad1 chromatin remodeler evicts nucleosomes generating accessible DNA. Free DNA is repackaged via DAXX-mediated nucleosome assembly with histone variant H3.3 in this dynamic heterochromatin state. Loss of H3.3 in mouse embryonic stem cells elicits a highly specific opening of interstitial heterochromatin with minimal effects on other silent or active regions of the genome.
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http://dx.doi.org/10.1038/s41467-020-18863-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547087PMC
October 2020

Incidence of Dementia and Associated Factors in the EPIC-Spain Dementia Cohort.

J Alzheimers Dis 2020 ;78(2):543-555

Murcia Biomedical Research Institute (IMIB-Arrixaca), Murcia, Spain.

Background: Dementia has become a public health priority as the number of cases continues to grow worldwide.

Objective: To assess dementia incidence and determinants in the EPIC-Spain Dementia Cohort.

Methods: 25,015 participants (57% women) were recruited from three Spanish regions between 1992-1996 and followed-up for over 20 years. Incident cases were ascertained through individual revision of medical records of potential cases. Crude and age-adjusted incidence rates (IR) of dementia and sub-types (Alzheimer's disease (AD), and non-AD) were calculated by sex. Neelson-Aalen cumulative incidence estimates at 10, 15, and 20 years were obtained for each sex and age group. Multivariate Royston-Parmar models were used to assess independent determinants.

Results: Global IR were higher in women for dementia and AD, and similar by sex for non-AD. IR ranged from 0.09 cases of dementia (95% confidence interval: 0.06-0.13) and 0.05 (0.03-0.09) of AD per 1000 person-years (py) 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 py) in those ≥85 years. Adjusted IR were consistently higher in women than men for overall dementia and AD. 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.

Conclusion: Dementia incidence increased with age and was higher among women, but showed no geographical pattern. Dementia risk was higher among subjects with lower education, not drinking alcohol, and presenting cardiovascular risk factors.
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http://dx.doi.org/10.3233/JAD-200774DOI Listing
May 2021

Modification of the risk of post-traumatic stress disorder (PTSD) by the 5-HTTLPR polymorphisms after Lorca's earthquakes (Murcia, Spain).

Psychiatry Res 2019 12 11;282:112640. Epub 2019 Nov 11.

Instituto de Neurociencias UMH-CSIC. Alicante, Spain; CIBER in Mental Health (CIBERSAM). Madrid, Spain.

Information of the modulation effect of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) on post-traumatic stress disorder (PTSD) after earthquakes is scarce and contradictory. A cross-sectional face-to-face interview survey of a representative sample of the adults was carried out after the Lorca (Spain) earthquakes (May 11, 2011). Socio-demographic variables, DSM-IV diagnostic assessment and earthquake-related stressors were obtained from the Composite International Diagnostic Interview (CIDI). The triallelic and biallelic classification of the 5-HTTLPR polymorphism were genotyped from buccal swabs. Multivariate logistic regression models were used to predict PTSD, including interaction terms to explore gene-environment (G x E) interactions. The vast majority (83%, n = 341) of the Lorca survey respondents (n = 412, 71% response rate) were genotyped. Both classifications of the 5-HTTLPR genotype were in Hardy-Weinberg equilibrium. Prior lifetime PTSD was the only variable that remained a significant predictor after adjustments. There were no significant main effects of earthquake related stressors or 5-HTTLPR. However, G x E interactions of 5-HTTLPR with high emotional impact and prior lifetime anxiety disorders were statistically significant. These results provide new evidence of the modulation effect of the 5-HTTLPR polymorphisms on PTSD risk. This information might characterize people at higher risk of developing PTSD after an earthquake exposure.
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http://dx.doi.org/10.1016/j.psychres.2019.112640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436333PMC
December 2019

[Food policies to prevent obesity and the main non-transmissible diseases in Spain: where there's a will there's a way].

Gac Sanit 2019 Nov - Dec;33(6):584-592. Epub 2019 Oct 1.

CIBER de Epidemiología y Salud Pública (CIBERESP), España; Unidad de Epidemiología de la Nutrición, Universidad Miguel Hernández, ISABIAL-FISABIO, Alicante, España.

Introduction: In Spain, one third of all children and two-thirds of adults suffer from excess weight, a condition that generates a direct excess medical cost of 2000 million Euros. Obesogenic food environments cause obesity by promoting the consumption of sugar-sweetened beverages and ultra-processed foods. Accordingly, we propose five priority policies capable of reversing the epidemic of obesity and related non-communicable diseases through the creation of healthy food environments.

The Power (poder In Spanish) Of Food Policies: Advertising (Publicidad): regulation of unhealthy food and drink advertisements carried by all media and targeted at children, and prohibition of sponsorships of congresses, conferences or sports events and endorsements by scientific associations or health professionals. Supply (Oferta): promotion of a 100% healthy supply of goods on sale in vending machines sited at educational, health and sports centres. Demand (Demanda): levying a tax of at least 20% on sugar-sweetened beverages, accompanied by subsidies or reduced taxes on healthy foods and availability of drinking water free of charge at all public venues and areas. Labelling (Etiquetado): effective application of the Nutri-Score through the use of incentives, regulation and public-tender mechanisms. Reformulation (Reformulación): revising and redrawing reformulation agreements with the industry, setting more ambitious goals and mandatory compliance.

A Final Thought: These five proposed interventions, all of which have been successfully applied in other countries, will serve to raise population awareness and have a positive impact on health and the economy, through reducing the health care costs of obesity and enhancing work productivity. These measures should form part of a wide-ranging transformation of the food system, with agri-food policies that foster the sustainable production of healthy foods.
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http://dx.doi.org/10.1016/j.gaceta.2019.05.009DOI Listing
April 2020

Childhood adversities and 5-HTTLPR polymorphism as risk factors of substance use disorders: retrospective case-control study in Murcia (Spain).

BMJ Open 2019 09 4;9(9):e030328. Epub 2019 Sep 4.

Instituto de Neurociencias, UMH-CSIC, Alicante, Spain.

Objective: To explore the separate and joint associations of childhood adversities and 5-HTTLPR polymorphism as risk factors for substance use disorders among adults. : : Retrospective case-control study.

Setting: Cases from the substance unit and controls from a representative sample of the adult general population in the metropolitan area of Murcia (Spain).

Participants: Cases were defined as outpatients 18 years old or older currently in the treatment for alcohol, opioids or cocaine use disorders in the clinical unit. Controls were randomly selected among individuals without substance use disorders who participated in the Psychiatric Enquiry to General Population in Southeast Spain-Murcia (PEGASUS-Murcia) project, a cross-sectional study of a representative sample of the adult general population. In all, 142 cases and 531 controls were interviewed and a subsample of 114 cases (80.3%) and 329 controls (62%) provided a biological sample.

Exposure: A history of 12 childhood adversities, lifetime mental disorders and sociodemographic variables was assessed with the Composite International Diagnostic Interview (CIDI)version 3.0). Buccal swabs were obtained to genotype the 5-HTTLPR polymorphism with the biallelic and the triallelic classification.

Main Outcome And Measure: Multivariable logistic regression models were performed to estimate adjusted ORs and 95% CI.

Results: Childhood adversities were associated with an elevated risk of substance use disorders (OR=5.77, 95% CI 3.46 to 9.61). Homozygotes for the short allele of the 5-HTTLPR polymorphism also showed the elevated risk of substance use disorders for the biallelic and triallelic classification: (1.97 (1.10 to 3.55) and 2.01 (1.11 to 3.64), respectively). No evidence for gene × environment interactions was found.

Conclusions: Childhood adversities and the 5-HTTLPR polymorphism are involved in the aetiology of substance use disorders though findings exploring the existence of a gene-environment interaction were inconclusive.
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http://dx.doi.org/10.1136/bmjopen-2019-030328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731914PMC
September 2019

Socioeconomic Effect of Education on Pancreatic Cancer Risk in Western Europe: An Update on the EPIC Cohorts Study.

Cancer Epidemiol Biomarkers Prev 2019 06;28(6):1089-1092

Department of Public Health, Aarhus University, Aarhus, Denmark.

Background: To analyze the potential effect of social inequality on pancreatic cancer risk in Western Europe, by reassessing the association within the European Prospective Investigation into Cancer and Nutrition (EPIC) Study, including a larger number of cases and an extended follow-up.

Methods: Data on highest education attained were gathered for 459,170 participants (70% women) from 10 European countries. A relative index of inequality (RII) based on adult education was calculated for comparability across countries and generations. Cox regression models were applied to estimate relative inequality in pancreatic cancer risk, stratifying by age, gender, and center, and adjusting for known pancreatic cancer risk factors.

Results: A total of 1,223 incident pancreatic cancer cases were included after a mean follow-up of 13.9 (±4.0) years. An inverse social trend was found in models adjusted for age, sex, and center for both sexes [HR of RII, 1.27; 95% confidence interval (CI), 1.02-1.59], which was also significant among women (HR, 1.42; 95% CI, 1.05-1.92). Further adjusting by smoking intensity, alcohol consumption, body mass index, prevalent diabetes, and physical activity led to an attenuation of the RII risk and loss of statistical significance.

Conclusions: The present reanalysis does not sustain the existence of an independent social inequality influence on pancreatic cancer risk in Western European women and men, using an index based on adult education, the most relevant social indicator linked to individual lifestyles, in a context of very low pancreatic cancer survival from (quasi) universal public health systems.

Impact: The results do not support an association between education and risk of pancreatic cancer.
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http://dx.doi.org/10.1158/1055-9965.EPI-18-1153DOI Listing
June 2019

Birth-sex cohort alcohol use transitions in the general population: the cross-sectional PEGASUS-Murcia project.

Adicciones 2020 Apr 1;32(2):94-104. Epub 2020 Apr 1.

Institut Universitaire de France, Université de Bordeaux, Laboratoire de Psychologie EA4139, Burdeos.

To examine the potential impact of prevalence of alcohol use in a birth-sex cohort on subsequent initiation and progression of alcohol use in the PEGASUS-Murcia project, a cross-sectional survey of a representative sample of non-institutionalized adults in Murcia (Spain). Data on lifetime history of alcohol use, DSM-IV use disorders, and remission were collected from 1,459 adults using face-to-face interviewers based on the Composite International Diagnostic Interview (CIDI 3.0). Life-table estimates based on survival functions for alcohol use age-of-onset and remission were used as time-varying predictors of subsequent individual-level alcohol use in discrete-time survival models. Nearly nine out of ten adults had a lifetime alcohol use history at time of interview. Of these lifetime users, 84.3% became regular users (>12 drinks a year) and 5.5-1.6% went on to meet criteria for DSM-IV alcohol abuse or dependence, respectively. By the age of 18, 70.9% of respondents had used alcohol, and one half (50.2%) had used regularly. Regular use sharply increased during early adulthood to reach 90.8% by age 22. Birth-sex cohort alcohol use was significantly and positively associated with increased odds of all subsequent transitions examined except for the transition from use to abuse. The findings highlight sensitive periods with rapid transitions to higher levels of alcohol use and emphasize the importance of cohort experiences in the full spectrum of stages of alcohol use. These results may contribute to predicting population-levels trends in alcohol-related problems in Spain.
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http://dx.doi.org/10.20882/adicciones.1067DOI Listing
April 2020

Ancient exapted transposable elements promote nuclear enrichment of human long noncoding RNAs.

Genome Res 2019 02 26;29(2):208-222. Epub 2018 Dec 26.

Department for BioMedical Research (DBMR), University of Bern, 3008 Bern, Switzerland.

The sequence domains underlying long noncoding RNA (lncRNA) activities, including their characteristic nuclear enrichment, remain largely unknown. It has been proposed that these domains can originate from neofunctionalized fragments of transposable elements (TEs), otherwise known as RIDLs (repeat insertion domains of lncRNA), although just a handful have been identified. It is challenging to distinguish functional RIDL instances against a numerous genomic background of neutrally evolving TEs. We here show evidence that a subset of TE types experience evolutionary selection in the context of lncRNA exons. Together these comprise an enrichment group of 5374 TE fragments in 3566 loci. Their host lncRNAs tend to be functionally validated and associated with disease. This RIDL group was used to explore the relationship between TEs and lncRNA subcellular localization. By using global localization data from 10 human cell lines, we uncover a dose-dependent relationship between nuclear/cytoplasmic distribution and evolutionarily conserved L2b, MIRb, and MIRc elements. This is observed in multiple cell types and is unaffected by confounders of transcript length or expression. Experimental validation with engineered transgenes shows that these TEs drive nuclear enrichment in a natural sequence context. Together these data reveal a role for TEs in regulating the subcellular localization of lncRNAs.
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http://dx.doi.org/10.1101/gr.229922.117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360812PMC
February 2019

Helicobacter pylori seroprevalence in Spain: influence of adult and childhood sociodemographic factors.

Eur J Cancer Prev 2019 07;28(4):294-303

Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública, CIBERESP).

Helicobacter pylori (H. pylori) chronic infection causes severe digestive diseases, including gastric cancer, and certain strains entail a higher risk. Risk factors for this infection are still not fully understood. The aim of this study was to describe the association of adult and childhood sociodemographic factors with the seroprevalence of H. pylori, and with CagA and VacA antigen-specific seropositivity among H. pylori-seropositive individuals in the Spanish adult population. Serum antibody reactivity to H. pylori proteins was evaluated using multiplex serology in 2555 population-based controls enrolled in the MCC-Spain study, a multicase-control study recruiting participants from 2008 to 2013 in different areas of Spain. H. pylori seroprevalence was defined as seropositivity against at least four bacterial proteins. Information on sociodemographics, lifestyles, and environmental exposures was collected through personal interviews. Prevalence ratios and 95% confidence intervals were estimated using Poisson regression models to assess the association of lifetime sociodemographic factors with H. pylori seroprevalence and with seropositivity for CagA and VacA. H. pylori seroprevalence was 87.2%. Seropositivity was statistically significantly higher in men, increased with age, BMI, and number of siblings, and decreased with education and socioeconomic family level at birth. Among H. pylori-seropositive individuals, seropositivity was 53.3% for CagA, 61.4% for VacA, and 38.8% for both CagA and VacA. Ever smokers had lower seroprevalence for CagA and VacA than never smokers. H. pylori seroprevalence among this Spanish adult population was high and one third of the population was seropositive for two well-known markers of gastric cancer risk: CagA and VacA. Sex, age, education, and BMI were associated with H. pylori seroprevalence.
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http://dx.doi.org/10.1097/CEJ.0000000000000483DOI Listing
July 2019

Ascertainment of Dementia Cases in the Spanish European Prospective Investigation into Cancer and Nutrition-Murcia Cohort.

Neuroepidemiology 2019 26;52(1-2):63-73. Epub 2018 Nov 26.

Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.

Background: Cohort studies generally focus on a particular disease, although they offer the possibility of evaluating different outcomes with minimal additional investment. The objective of this study was to describe the methodology used to assess dementia in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Murcia study.

Methods: The EPIC-Murcia cohort consists of 8,515 healthy participants (68% women, aged 30-70 years), recruited between 1992 and 1996 and followed up for over 20 years. Incident cases were ascertained by a 2-step protocol: a record linkage with health databases to identify potential events and a review of medical records of potential cases to validate incident cases.

Results: Overall, 1,202 potential cases were identified, and 275 dementia cases were validated. Medical reports were the source of information in 243 cases, with complete neurological information in 227, and a high degree of certainty of the diagnosis in 229 cases. P70 (dementia code) and/or antidementia drugs and/or ICD codes identified 259 cases (sensitivity: 94.2%, 95% CI 90.7-96.6; specificity: 98.1%, 95% CI 97.8-98.4).

Conclusion: Ascertainment of incident dementia in the EPIC-Murcia cohort study was feasible using information from medical records. This systematic 2-step validation protocol is proposed as a feasible way to ascertain dementia in cohort studies originally designed for other endpoints.
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http://dx.doi.org/10.1159/000493209DOI Listing
December 2019

Uncommon cause of liver abscess.

Clin Case Rep 2018 Aug 1;6(8):1649-1650. Epub 2018 Jul 1.

Hospital Santa Cecilia São Paulo Brazil.

Gastrointestinal perforation by fishbone causing a liver abscess is a rare entity, but should be included in the differential diagnosis to avoid delay in the treatment.
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http://dx.doi.org/10.1002/ccr3.1691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099009PMC
August 2018

Complex Care Needs in Multiple Chronic Conditions: Population Prevalence and Characterization in Primary Care. A Study Protocol.

Int J Integr Care 2018 May 25;18(2):16. Epub 2018 May 25.

Catalan Institute of Health, Barcelona, ES.

Background: Chronicity, and particularly complex care needs for people with chronic diseases is one of the main challenges of health systems.

Objective: To determine the population prevalence of people with chronic diseases and complex care needs and to characterize these needs considering features of health and social complexity in Primary Care.

Design: Cross-sectional population-based study.

Scope: Patients who have one or more chronic health conditions from three Primary Care urban centres of a reference population of 43.647 inhabitants older than 14 years old.

Methodology: Data will be obtained from the review of electronical medical records. Complexity will be defined by: 1) the independent clinical judgment of primary care physicians and nurses and 2) the aid of three complexity domains (clinical and social). Patients with advanced chronic disease and limited life prognosis will be also described.

Conclusions: This research protocol intends to describe and analyse complex care needs from a primary care professional perspective in order to improve knowledge of complexity beyond multimorbidity and previous consumption of health resources. Knowing about health and social complexity with a more robust empirical basis could help for a better integration of social and health policies and a more proactive and differentiated care approach in this most vulnerable population.
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http://dx.doi.org/10.5334/ijic.3292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095050PMC
May 2018

Correlation between meteorological parameters and nitrogen compounds present in wastewater in the formation of nitrous oxide in soils.

J Air Waste Manag Assoc 2018 12 25;68(12):1357-1365. Epub 2018 Sep 25.

c Department of Environmental and Energy , National Council for Science and Technology (CONACYT), Research Center of Advanced Materials S.C. (CIMAV) , Chih , Mexico.

In the present work, nitrous oxide emissions were estimated [mg/L] by the use of lysimeters under the closed chamber technique for a six month period. The lysimeters were classified by the type of irrigation used: one for drinking water, and the other for treated wastewater. Each lysimeter had two different types of soil (sand and clay), based on the types of soil in Chihuahua City, Mexico. An additional classification based on the depth was done (reticular and vadose zone). Each zone collected gas by the use of a closed chamber technique, allowing the samples to be taken for subsequent quantification and analysis by gas chromatography. A statistical analysis of variance (ANOVA) and principal components analysis (PCA) were conducted to identify the most influential variables or parameters in the formation of nitrous oxide. The variables that were considered for analysis were total Kjeldahl nitrogen (TKN), ammoniacal nitrogen (NH3-N), nitrate nitrogen (NO3-N), and nitrite nitrogen (NO2-N), along with meteorological parameters. In total, 58944 mg/L of N2O were emitted during the measurement period. The results showed that concentration emissions of N2O where the type of soil is sandy were smaller than those of clay soil, while the mean concentration in the vadose zone was higher than those in the reticular zone, regardless the type of soil. The parameters that showed greater influence in the N2O emissions were NO2-N and NO3-N concentrations. Temperature also played an important role in the emissions (the highest emissions were emitted during the cold months). Furthermore, denitrification appeared to be the dominant process in the production of nitrous oxide in soils. Implications: Nitrous oxide (NO) emissions produced in lysimeters with two types of soil (sand and clay) at two different depths (vadose and reticular zones) using treated waste water showed that the higher emissions of NO are derived from clay soils in vadose zone; it could be due to the formation of clogging that favors the formation of anoxic conditions for the denitrification process. The parameters that showed more influence in the NO emissions were nitrite (NO-N) and nitrate (NO-N) concentrations along with the temperature.
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http://dx.doi.org/10.1080/10962247.2018.1511488DOI Listing
December 2018

[Corrigendum a: Estudio multicaso-control de base poblacional de tumores comunes en España (MCC-Spain): razón y diseño del estudio (Gaceta Sanitaria 2015;29:308-15)].

Gac Sanit 2018 Sep - Oct;32(5):501. Epub 2018 Jul 20.

Centre for Research in Environmental Epidemiology (CREAL), Barcelona, España; IMIM (Hospital del Mar Medical Research Institute), Barcelona, España; Universitat Pompeu Fabra (UPF), Barcelona, España; CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, España; School of Public Health, Athens, Grecia.

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http://dx.doi.org/10.1016/j.gaceta.2018.04.004DOI Listing
July 2018

Moderate egg consumption and all-cause and specific-cause mortality in the Spanish European Prospective into Cancer and Nutrition (EPIC-Spain) study.

Eur J Nutr 2019 Aug 15;58(5):2003-2010. Epub 2018 Jun 15.

Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Avda Gran Via 199-203, L'Hospitalet de Llobregat, 08907, Barcelona, Spain.

Purpose: Dietary guidelines for egg consumption for general population differ among public health agencies. Our aim was to investigate the association between egg intake and both all-cause and specific-cause of mortality in a Mediterranean population.

Methods: The European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort included 40,621 men and women aged 29-69 years old in the nineties from 5 Spanish regions. After a mean of 18 years of follow-up, 3,561 deaths were recorded, of which 1,694 were from cancer, 761 from CVD, and 870 from other causes. Data on egg consumption was collected using a validated diet history at recruitment. Cox proportional hazards models, adjusted for confounders, were used in the analyses.

Results: The mean (standard deviation) egg consumption was 22.0 g/day (15.8) and 30.9 g/day (23.1) in women and men, respectively. No association was observed between egg consumption and all-cause mortality for the highest vs the lowest quartile (HR 1.01; 95% CI 0.91-1.11; P trend = 0.96). Likewise, no association was observed with cancer and cardiovascular diseases mortality. However, an inverse association was found between egg consumption and deaths for other causes (HR 0.76; 95% CI 0.63-0.93; P trend = 0.003), particularly for deaths from the nervous system (HR 0.59; 95% CI 0.35-1.00; P trend = 0.036). No interaction was detected with the adherence to Mediterranean diet.

Conclusions: This study shows no association between moderate egg consumption, up to 1 egg per day, and main causes of mortality in a large free-living Mediterranean population.
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http://dx.doi.org/10.1007/s00394-018-1754-6DOI Listing
August 2019

[More than a decade improving medical and judicial certification in mortality statistics of death causes].

Rev Esp Salud Publica 2018 Jun 6;92. Epub 2018 Jun 6.

Servicio de Epidemiología. Consejería de Salud. Murcia. España.

Objective: After the return of Spain to democracy and the regional assumption of government powers, actions were initiated to improve the mortality statistics of death causes. The objective of this work was to describe the evolution of the quality activities improvements into the statistics of death causes on Murcia's region during 1989 to 2011.

Methods: Descriptive epidemiological study of all death documents processed by the Murcia mortality registry. Use of indicators related to the quality of the completion of death in medical and judicial notification; recovery of information on the causes and circumstances of death; and impact on the statistics of ill-defined, unspecific and less specific causes.

Results: During the study period, the medical notification without a temporary sequence on the death certificate (DC) has decreased from 46% initial to 21% final (p less than 0.001). Information retrieval from sources was successful in 93% of the cases in 2001 compared to 38%, at the beginning of the period (p less than 0.001). Regional rates of ill-defined and unspecific causes fell more than national ones, and they were in the last year with a differential of 10.3 (p less than 0.001) and 2.8 points (p=0.001), respectively.

Conclusions: The medical death certification improved in form and suitability. Regulated recovery of the causes of death and circumstances corrected medical and judicial information. The Murcia's region presented lower rates in less specified causes and ill-defined entities than national averages.
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June 2018

Dietary intake of total polyphenol and polyphenol classes and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Eur J Epidemiol 2018 Nov 15;33(11):1063-1075. Epub 2018 May 15.

CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

Polyphenols may play a chemopreventive role in colorectal cancer (CRC); however, epidemiological evidence supporting a role for intake of individual polyphenol classes, other than flavonoids is insufficient. We evaluated the association between dietary intakes of total and individual classes and subclasses of polyphenols and CRC risk and its main subsites, colon and rectum, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The cohort included 476,160 men and women from 10 European countries. During a mean follow-up of 14 years, there were 5991 incident CRC cases, of which 3897 were in the colon and 2094 were in the rectum. Polyphenol intake was estimated using validated centre/country specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, a doubling in total dietary polyphenol intake was not associated with CRC risk in women (HR = 1.06, 95% CI 0.99-1.14) or in men (HR = 0.97, 95% CI 0.90-1.05), respectively. Phenolic acid intake, highly correlated with coffee consumption, was inversely associated with colon cancer in men (HR = 0.91, 95% CI 0.85-0.97) and positively associated with rectal cancer in women (HR = 1.10, 95% CI 1.02-1.19); although associations did not exceed the Bonferroni threshold for significance. Intake of other polyphenol classes was not related to colorectal, colon or rectal cancer risks. Our study suggests a possible inverse association between phenolic acid intake and colon cancer risk in men and positive with rectal cancer risk in women.
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http://dx.doi.org/10.1007/s10654-018-0408-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760973PMC
November 2018

Fabry disease in the Spanish population: observational study with detection of 77 patients.

Orphanet J Rare Dis 2018 04 10;13(1):52. Epub 2018 Apr 10.

Rare Diseases and Pediatric Medicine Research Group, Galicia Sur Health Research Institute (IIS Galicia Sur). SERGAS-UVIGO, Vigo, Spain.

Background: Fabry disease is a multisystemic lysosomal storage disorder caused by the impairment of α-galactosidase A. The incidence of this rare disease is underestimated due to delayed diagnosis. Moreover, the management of the identified subjects is often complicated by the detection of variants of unclear diagnostic interpretation, usually identified in screening studies. We performed an observational study based on biochemical and genetic analysis of 805 dried blood spot samples from patients with clinical symptoms or family history of this pathology, which were collected from 109 Spanish hospitals, all over the country.

Results: We identified 77 new diagnosed patients with mutations related to classical Fabry disease, as well as 2 subjects with c.374A > T; p.His125Leu, a possible new mutation that need to be confirmed. Additionally, we detected 8 subjects carrying genetic variants possibly linked to late onset Fabry disease (p.Arg118Cys and p.Ala143Thr), 4 cases with polymorphism p.Asp313Tyr and 36 individuals with single nucleotide polymorphisms in intronic regions of GLA. Five of the identified mutations (c.431delG; c.1182delA; c.374A > T; c.932 T > C; c.125 T > A; c.778G > A), which were associated with a classical phenotype have not been previously described. Moreover 3 subjects presenting complex haplotypes made up by the association of intronic variants presented impaired levels of GLA transcripts and Gb3 deposits in skin biopsy.

Conclusions: Enzymatic screening for Fabry Disease in risk population (2 or more clinical manifestations or family history of the disease) helped to identify undiagnosed patients and unravel the impairment of GLA expression in some subjects with complex haplotypes.
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http://dx.doi.org/10.1186/s13023-018-0792-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891901PMC
April 2018

Sequence data and association statistics from 12,940 type 2 diabetes cases and controls.

Sci Data 2017 12 19;4:170179. Epub 2017 Dec 19.

Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (>80% of low-frequency coding variants in ~82 K Europeans via the exome chip, and ~90% of low-frequency non-coding variants in ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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http://dx.doi.org/10.1038/sdata.2017.179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735917PMC
December 2017

ProphTools: general prioritization tools for heterogeneous biological networks.

Gigascience 2017 12;6(12):1-8

Department of Computer Science and Artificial Intelligence, University of Granada, Granada, Spain.

Background: Networks have been proven effective representations for the analysis of biological data. As such, there exist multiple methods to extract knowledge from biological networks. However, these approaches usually limit their scope to a single biological entity type of interest or they lack the flexibility to analyze user-defined data.

Results: We developed ProphTools, a flexible open-source command-line tool that performs prioritization on a heterogeneous network. ProphTools prioritization combines a Flow Propagation algorithm similar to a Random Walk with Restarts and a weighted propagation method. A flexible model for the representation of a heterogeneous network allows the user to define a prioritization problem involving an arbitrary number of entity types and their interconnections. Furthermore, ProphTools provides functionality to perform cross-validation tests, allowing users to select the best network configuration for a given problem. ProphTools core prioritization methodology has already been proven effective in gene-disease prioritization and drug repositioning. Here we make ProphTools available to the scientific community as flexible, open-source software and perform a new proof-of-concept case study on long noncoding RNAs (lncRNAs) to disease prioritization.

Conclusions: ProphTools is robust prioritization software that provides the flexibility not present in other state-of-the-art network analysis approaches, enabling researchers to perform prioritization tasks on any user-defined heterogeneous network. Furthermore, the application to lncRNA-disease prioritization shows that ProphTools can reach the performance levels of ad hoc prioritization tools without losing its generality.
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http://dx.doi.org/10.1093/gigascience/gix111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751048PMC
December 2017

Ovarian cancer early detection by circulating CA125 in the context of anti-CA125 autoantibody levels: Results from the EPIC cohort.

Int J Cancer 2018 04 11;142(7):1355-1360. Epub 2017 Dec 11.

Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, Spain.

CA125 is the best ovarian cancer early detection marker to date; however, sensitivity is limited and complementary markers are required to improve discrimination between ovarian cancer cases and non-cases. Anti-CA125 autoantibodies are observed in circulation. Our objective was to evaluate whether these antibodies (1) can serve as early detection markers, providing evidence of an immune response to a developing tumor, and (2) modify the discriminatory capacity of CA125 by either masking CA125 levels (resulting in lower discrimination) or acting synergistically to improve discrimination between cases and non-cases. We investigated these objectives using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (EPIC) including 250 cases diagnosed within 4 years of blood collection and up to four matched controls. Circulating CA125 antigen and antibody levels were quantified using an electrochemiluminescence assay. Adjusted areas under the curve (aAUCs) by 2-year lag-time intervals were calculated using conditional logistic regression calibrated toward the absolute risk estimates from a pre-existing epidemiological risk model as an offset-variable. Anti-CA125 levels alone did not discriminate cases from controls. For cases diagnosed <2 years after blood collection, discrimination by CA125 antigen was suggestively higher with higher anti-CA125 levels (aAUC, highest antibody tertile: 0.84 [0.76-0.92]; lowest tertile: 0.76 [0.67-0.86]; p  = 0.06). We provide the first evidence of potentially synergistic discrimination effects of CA125 and anti-CA125 antibodies in ovarian early detection. If these findings are replicated, evaluating CA125 in the context of its antibody may improve ovarian cancer early detection.
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http://dx.doi.org/10.1002/ijc.31164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805613PMC
April 2018

High adherence to the Western, Prudent, and Mediterranean dietary patterns and risk of gastric adenocarcinoma: MCC-Spain study.

Gastric Cancer 2018 May 14;21(3):372-382. Epub 2017 Nov 14.

Cancer Epidemiology Unit, National Centre for Epidemiology, Instituto de Salud Carlos III, Av/Monforte de Lemos, 5, 28029, Madrid, Spain.

Background: The influence of dietary habits on the development of gastric adenocarcinoma is not clear. The objective of the present study was to explore the association of three previously identified dietary patterns with gastric adenocarcinoma by sex, age, cancer site, and morphology.

Methods: MCC-Spain is a multicase-control study that included 295 incident cases of gastric adenocarcinoma and 3040 controls. The association of the Western, Prudent, and Mediterranean dietary patterns-derived in another Spanish case-control study-with gastric adenocarcinoma was assessed using multivariable logistic regression models with random province-specific intercepts and considering a possible interaction with sex and age. Risk according to tumor site (cardia, non-cardia) and morphology (intestinal/diffuse) was evaluated using multinomial regression models.

Results: A high adherence to the Western pattern increased gastric adenocarcinoma risk [odds ratio (95% confidence interval), 2.09 (1.31; 3.33)] even at low levels [odds ratio (95% confidence interval), 1.63 (1.05; 2.52)]. High adherence to the Mediterranean dietary pattern could prevent gastric adenocarcinoma [odds ratio (95% confidence interval), 0.53 (0.34; 0.82)]. Although no significant heterogeneity of effects was observed, the harmful effect of the Western pattern was stronger among older participants and for non-cardia adenocarcinomas, whereas the protective effect of the Mediterranean pattern was only observed among younger participants and for non-cardia tumors.

Conclusion: Decreasing the consumption of fatty and sugary products and of red and processed meat in favor of an increase in the intake of fruits, vegetables, legumes, olive oil, nuts, and fish might prevent gastric adenocarcinoma.
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http://dx.doi.org/10.1007/s10120-017-0774-xDOI Listing
May 2018
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