A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12

Background: Colorectal cancer (CRC) is a disease of complex aetiology, with much of the expected inherited risk being due to several common low risk variants. Genome-Wide Association Studies (GWAS) have identified 20 CRC risk variants. Nevertheless, these have only been able to explain part of the missing heritability. Moreover, these signals have only been inspected in populations of Northern European origin. Results: Thus, we followed the same approach in a Spanish cohort of 881 cases and 667 controls. Sixty-four variants at 24 loci were found to be associated with CRC at p-values <10-5. We therefore evaluated the 24 loci in another Spanish replication cohort (1481 cases and 1850 controls). Two of these SNPs, rs12080929 at 1p33 (P-replication=0.042; P-pooled=5.523x10(-03); OR (CI95%)=0.866(0.782-0.959)) and rs11987193 at 8p12 (P-replication=0.039; P-pooled=6.985x10(-5); OR (CI95%)=0.786(0.705-0.878)) were replicated in the second Phase, although they did not reach genome-wide statistical significance. Conclusions: We have performed the first CRC GWAS in a Southern European population and by these means we were able to identify two new susceptibility variants at 1p33 and 8p12 loci. These two SNPs are located near the SLC5A9 and DUSP4 loci, respectively, which could be good functional candidates for the association signals. We therefore believe that these two markers constitute good candidates for CRC susceptibility loci and should be further evaluated in other larger datasets. Moreover, we highlight that were these two SNPs true susceptibility variants, they would constitute a decrease in the CRC missing heritability fraction.

Analysis of dietary pattern impact on weight status for personalised nutrition through on-line advice: the Food4Me Spanish cohort

Obesity prevalence is increasing. The management of this condition requires a detailed analysis of the global risk factors in order to develop personalised advice. This study is aimed to identify current dietary patterns and habits in Spanish population interested in personalised nutrition and investigate associations with weight status. Self-reported dietary and anthropometrical data from the Spanish participants in the Food4Me study, were used in a multidimensional exploratory analysis to define specific dietary profiles. Two opposing factors were obtained according to food groups’ intake: Factor 1 characterised by a more frequent consumption of traditionally considered unhealthy foods; and Factor 2, where the consumption of “Mediterranean diet” foods was prevalent. Factor 1 showed a direct relationship with BMI (β = 0.226; r2 = 0.259; p < 0.001), while the association with Factor 2 was inverse (β = −0.037; r2 = 0.230; p = 0.348). A total of four categories were defined (Prudent, Healthy, Western, and Compensatory) through classification of the sample in higher or lower adherence to each factor and combining the possibilities. Western and Compensatory dietary patterns, which were characterized by high-density foods consumption, showed positive associations with overweight prevalence. Further analysis showed that prevention of overweight must focus on limiting the intake of known deleterious foods rather than exclusively enhance healthy products.

Validity of the physical activity questionnaires IPAQ-SF and GPAQ for Cancer Survivors: Insights from a Spanish cohort

Regular physical activity (PA) decreases mortality risk in survivors of breast and colorectal cancer. Such impacts of exercise have prompted initiatives designed both to promote and adequately monitor PA in cancer survivors. This study examines the validity of 2 widely used self-report methods for PA determination, the International Physical Activity Questionnaire short version (IPAQ-SF) and Global Physical Activity Questionnaire (GPAQ). Both instruments were compared with the triaxial accelerometry (Actigraph) method as an objective reference standard. Study participants were 204 cancer survivors (both sexes, aged 18-79 years). Compared with accelerometry, both questionnaires significantly overestimated PA levels (across all intensities) and underestimated physical inactivity levels. No differences were detected between the 2 questionnaires except for a shorter inactivity time estimated by GPAQ (p=0.001). The Bland and Altman method confirmed that both questionnaires overestimated all PA levels. Receiver operating characteristic (ROC) analysis classified IPAQ and GPAQ as fair and poor predictors, respectively, of the proportions of survivors fulfilling international PA recommendations (≥150 min·week-1 of moderate-vigorous PA). IPAQ-SF showed a higher sensitivity but lower specificity than GPAQ. Our data do not support the use of IPAQ-SF or GPAQ to determine PA or inactivity levels in cancer survivors.

Análisis económico de las vacunas 10-valente y 13-valente contra neumococo: revisión sistemática

Introducción: Las vacunas clásicamente han representado un método económico y eficaz para el control y prevención de múltiples enfermedades infecciosas. En los últimos años se han introducido nuevas vacunas contra neumococo a precios elevados, y los diferentes análisis económicos a nivel mundial de estas vacunas no muestran tendencias. El objetivo de este trabajo era resumir la evidencia existente a través de los diferentes estudios económicos evaluando las dos vacunas de segunda generación contra neumococo en la población a riesgo. Metodología: En este trabajo se realizo una revisión sistemática de la literatura en 8 bases de datos localizadas en diferentes partes del mundo y también que tuvieran literatura gris. Los artículos fueron inicialmente evaluados acorde a su titulo y resumen, posteriormente los elegidos se analizaron en su totalidad. Resultados: Se encontraron 404 artículos, de los cuales 20 fueron incluidos en el análisis final. Se encontró que la mayoría de los estudios se realizaron en áreas donde la enfermedad tiene una carga baja, como es Norte América y Europa, mientras que en los lugares del mundo donde la carga es mas alta, se realizaron pocos estudios. De igual manera se observo que la mayoría de los estudios mostraron por los menos ser costo efectivos respecto a la no vacunación, y en su totalidad las dos vacunas de segunda generación mostraron costo efectividad respecto a la vacunación con PCV-7. Los resultados de los estudios son muy heterogéneos, hasta dentro del mismo país, señalando la necesidad de guías para la conducción de este tipo de estudios. De igual manera, la mayoría de los estudios fueron financiados por farmacéuticas, mientras en un numero muy reducido por entes gubernamentales. Conclusiones: La mayoría de los estudios económicos sobre las vacunas de segunda generación contra neumococo han sido realizados en países con un alto índice de desarrollo económico y patrocinados por farmacéuticas. Dado que la mayoría de la carga de la enfermedad se encuentran en regiones con un menor nivel de desarrollo económico se deberían realizar mas en estas zonas. De igual manera, al ser la vacunación un asunto de salud publica y con un importante impacto económico los gobiernos deberían estar mas involucrados en los mismos.

Toward a comprehensive care of HIV patients: Finding a strategy to detect depression in a Spanish HIV cohort

Depression is a common but frequently undiagnosed feature in individuals with HIV infection. To find a strategy to detect depression in a non-specialized clinical setting, the overall performance of the Hospital Anxiety and Depression Scale (HADS) and the depression identification questions proposed by the European AIDS Clinical Society (EACS) guidelines were assessed in a descriptive cross-sectional study of 113 patients with HIV infection. The clinician asked the two screening questions that were proposed under the EACS guidelines and requested patients to complete the HADS. A psychiatrist or psychologist administered semi-structured clinical interviews to yield psychiatric diagnoses of depression (gold standard). A receiver operating characteristic (ROC) analysis for the HADS-Depression (HADS-D) subscale indicated that the best sensitivity and specificity were obtained between the cut-off points of 5 and 8, and the ROC curve for the HADS-Total (HADS-T) indicated that the best cut-off points were between 12 and 14. There were no statistically significant differences in the correlations of the EACS (considering positive responses to one [A] or both questions [B]), the HADS-D ≥ 8 or the HADS-T ≥ 12 with the gold standard. The study concludes that both approaches (the two EACS questions and the HADS-D subscale) are appropriate depression-screening methods in HIV population. We believe that using the EACS-B and the HADS-D subscale in a two-step approach allows for rapid, assumable and accurate clinical diagnosis in non-psychiatric hospital settings.

Prognostic Role of Host Cyclooxygenase and Cytokine Genotypes in a Caucasian Cohort of Patients with Gastric Adenocarcinoma

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Relationship between body image disturbance and incidence of depression: the SUN prospective cohort

[EN] Background: Body image disturbance is an increasing problem in Western societies and is associated with a number of mental health outcomes including anorexia, bulimia, body dysmorphia, and depression. The aim of this study was to assess the association between body image disturbance and the incidence of depression. Methods: This study included 10,286 participants from a dynamic prospective cohort of Spanish university graduates, who were followed-up for a median period of 4.2 years (Seguimiento Universidad de Navarra – the SUN study). The key characteristic of the study is the permanently open recruitment that started in 1999. The baseline questionnaire included information about body mass index (BMI) and the nine figure schemes that were used to assess body size perception. These variables were grouped according to recommended classifications and the difference between BMI and body size perception was considered as a proxy of body image disturbance. A subject was classified as an incident case of depression if he/she was initially free of depression and reported a physician-made diagnosis of depression and/or the use of antidepressant medication in at least one of the follow-up questionnaires. The association between body image disturbance and the incidence of depression was estimated by calculating the multivariable adjusted Odds Ratio (OR) and its 95% Confidence Interval (95% CI), using logistic regression models. Results: The cumulative incidence of depression during follow-up in the cohort was 4.8%. Men who underestimated their body size had a high percentage of overweight and obesity (50.1% and 12.6%, respectively), whereas women who overestimated their body size had a high percentage of underweight (87.6%). The underestimation exhibited a negative association with the incidence of depression among women (OR: 0.72, 95% CI: 0.54 – 0.95), but this effect disappeared after adjusting for possible confounding variables. The proportion of participants who correctly perceived their body size was high (53.3%) and gross misperception was seldom found, with most cases selecting only one silhouette below (42.7%) or above (2.6%) their actual BMI. Conclusion: We found no association between body image disturbance and subsequent depression in a cohort of university graduates in Spain.

INFANT MORTALITY IN THE MEXICAN AMERICAN COMMUNITY: AN ANALYSIS OF DIFFERENTIALS IN INFANT, NEONATAL, AND POSTNEONATAL MORTALITY BY ETHNICITY AND PARENTAL NATIVITY, 1974-75 SINGLE LIVE BIRTH COHORT, HARRIS COUNTY, TEXAS

The paradoxically low infant mortality rates for Mexican Americans in Texas have been attributed to inaccuracies in vital registration and idiosyncracies in Mexican migration in rural areas along the U.S.-Mexico border. This study examined infant (IMR), neonatal (NMR), and postneonatal (PNMR) mortality rates of Mexican Americans in an urban, non-border setting, using linked birth and death records of the 1974-75 single live birth cohort (N = 68,584) in Harris County, Texas, which includes the city of Houston and is reported to have nearly complete birth and death registration. The use of parental nativity with the traditional Spanish surname criterion made it possible to distinguish infants of Mexican-born immigrants from those of Blacks, Anglos, other Hispanics, and later-generation, more Anglicized Mexican Americans. Mortality rates were analyzed by ethnicity, parental nativity, and cause of death, with respect to birth weight, birth order, maternal age, legitimacy status, and time of first prenatal care.^ While overall IMRs showed Spanish surname rates slightly higher than Anglo rates, infants of Mexican-born immigrants had much lower NMRs than did Anglos, even for moderately low birth weight infants. However, among infants under 1500 grams, presumably unable to be discharged home in the neonatal period, Mexican Americans had the highest NMR. The inconsistency suggested unreported deaths for Mexican American low birth weight infants after hospital discharge. The PNMR of infants of Mexican immigrants was also lower than for Anglos, and the usual mortality differentials were reversed: high-risk categories of high birth order, high maternal age, and late/no prenatal care had the lowest PNMRs. Since these groups' characteristics are congruent with those of low-income migrants, the data suggested the possibility of migration losses. Cause of death analysis suggested that prematurity and birth injuries are greater problems than heretofore recognized among Mexican Americans, and that home births and "shoebox burials" may be unrecorded even in an urban setting.^ Caution is advised in the interpretation of infant mortality rates for a Spanish surname population of Mexican origin, even in an urban, non-border area with reportedly excellent birth and death registration. ^

Validation of a Spanish Version of the Lille Apathy Rating Scale for Parkinson’s Disease

Introduction. To date, no rating scales for detecting apathy in Parkinson’s disease (PD) patients have been validated in Spanish. For this reason, the aim of this study was to validate a Spanish version of Lille apathy rating scale (LARS) in a cohort of PD patients from Spain. Participants and Methods. 130 PD patients and 70 healthy controls were recruited to participate in the study. Apathy was measured using the Spanish version of LARS and the neuropsychiatric inventory (NPI). Reliability (internal consistency, test-retest, and interrater reliability) and validity (construct, content, and criterion validity) were measured. Results. Interrater reliability was 0.93. Cronbach’s α for LARS was 0.81. The test-retest correlation coefficient was 0.97. The correlation between LARS and NPI scores was 0.61. The optimal cutoff point under the ROC curve was , whereas the value derived from healthy controls was . The prevalence of apathy in our population tested by LARS was 42%. Conclusions. The Spanish version of LARS is a reliable and useful tool for diagnosing apathy in PD patients. Total LARS score is influenced by the presence of depression and cognitive impairment. However, both disorders are independent identities with respect to apathy. The satisfactory reliability and validity of the scale make it an appropriate instrument for screening and diagnosing apathy in clinical practice or for research purposes.

Aging, retirement, and changes in physical activity : prospective cohort findings from the globe study

There is increased recognition that determinants of health should be investigated in a life-course perspective. Retirement is a major transition in the life course and offers opportunities for changes in physical activity that may improve health in the aging population. The authors examined the effect of retirement on changes in physical activity in the GLOBE Study, a prospective cohort study known by the Dutch acronym for "Health and Living Conditions of the Population of Eindhoven and surroundings," 1991–2004. They followed respondents (n = 971) by postal questionnaire who were employed and aged 40–65 years in 1991 for 13 years, after which they were still employed (n = 287) or had retired (n = 684). Physical activity included 1) work-related transportation, 2) sports participation, and 3) nonsports leisure-time physical activity. Multinomial logistic regression analyses indicated that retirement was associated with a significantly higher odds for a decline in physical activity from work-related transportation (odds ratio (OR) = 3.03, 95% confidence interval (CI): 1.97, 4.65), adjusted for sex, age, marital status, chronic diseases, and education, compared with remaining employed. Retirement was not associated with an increase in sports participation (OR = 1.12, 95% CI: 0.71, 1.75) or nonsports leisure-time physical activity (OR = 0.80, 95% CI: 0.54, 1.19). In conclusion, retirement introduces a reduction in physical activity from work-related transportation that is not compensated for by an increase in sports participation or an increase in nonsports leisure-time physical activity.

The supervision of doctoral dissertations using a collaborative cohort model

The Collaborative Cohort Model (CCM) for research supervision was developed and piloted as an alternative to the Apprentice Master Model (AMM), which is currently used with most doctoral dissertations. The CCM was developed in response to concerns about completion rates and the quality of research supervision. The feedback from the initial cohort of doctoral students who have experienced the model is presented.

Maternal age and paternal age are associated with distinct childhood behavioural outcomes in a general population birth cohort

Abstract Background Recent studies show that advanced paternal age (APA) is associated with an increased risk of neurodevelopmental disorders such as autism, bipolar disorder and schizophrenia. A body of evidence also suggests that individuals who develop schizophrenia show subtle deviations in a range of behavioural domains during their childhood. The aim of the study was to examine the relationship between paternal and maternal ages and selected behavioural measures in children using a large birth cohort. Method Participants were singleton children (n = 21,753) drawn from the US Collaborative Perinatal Project. The outcome measures were assessed at 7 years. The main analyses examined the relationship between parental age and behavioural measures when adjusted for a range of potentially confounding variables, including age of the other parent, maternal race, socio-economic measures, sex, gestation length, maternal marital status, parental mental illness, and child's age-at-testing. Results Advanced paternal age was associated with a significantly increased risk of adverse ‘externalizing’ behaviours at age seven years. For every five year increase in paternal age, the odds of higher ‘externalizing’ behaviours was increased by 12% (OR = 1.12; 95% CI = 1.03, 1.21, p < 0.0001). The relationship persisted after adjusting for potential confounding factors. ‘Internalizing’ behavioural outcome was not associated with advanced paternal age. In contrast, advanced maternal age was significantly protective against adverse ‘externalizing’ behavioural outcomes, but associated with an increased risk of adverse ‘internalizing’ behavioural outcomes. Discussion The offspring of older fathers show a distinctly different pattern of behaviours compared to the offspring of older mothers. The diverse socio-cultural and biologically-mediated factors that underpin these findings remain to be clarified. In light of secular trends related to delayed parenthood, the mechanisms underlying these findings warrant closer scrutiny.

Psychopathology during childhood and adolescence predicts delusional-like experiences in adults : a 21-year birth cohort study

Objective: Community surveys have shown that many otherwise well individuals report delusional-like experiences. The authors examined psychopathology during childhood and adolescence as a predictor of delusional-like experiences in young adulthood. ---------- Method: The authors analyzed prospective data from the Mater-University of Queensland Study of Pregnancy, a birth cohort of 3,617 young adults born between 1981 and 1983. Psychopathology was measured at ages 5 and 14 using the Child Behavior Checklist (CBCL) and at age 14 using the Youth Self-Report (YSR). Delusional-like experiences were measured at age 21 using the Peters Delusional Inventory. The association between childhood and adolescent symptoms and later delusional-like experiences was examined using logistic regression. ---------- Results: High CBCL scores at ages 5 and 14 predicted high levels of delusional-like experiences at age 21 (odds ratios for the highest versus the other quartiles combined were 1.25 and 1.85, respectively). Those with YSR scores in the highest quartile at age 14 were nearly four times as likely to have high levels of delusional-like experiences at age 21 (odds ratio=3.71). Adolescent-onset psychopathology and continuous psychopathology through both childhood and adolescence strongly predicted delusional-like experiences at age 21. Hallucinations at age 14 were significantly associated with delusional-like experiences at age 21. The general pattern of associations persisted when adjusted for previous drug use or the presence of nonaffective psychoses at age 21. ---------- Conclusion: Psychopathology during childhood and adolescence predicts adult delusional-like experiences. Understanding the biological and psychosocial factors that influence this developmental trajectory may provide clues to the pathogenesis of psychotic-like experiences.