Exploring ethnic and racial differences in intraocular pressure and glaucoma: The Canadian Longitudinal Study on aging.

Purpose: To determine whether self-reported race/ethnicity is associated with intraocular pressure (IOP) and glaucoma and to explore whether any associations are due to social, behavioral, genetic, or health differences. Design: Cross-sectional analysis of population-based data. Methods: We used the Canadian Longitudinal Study on Aging Comprehensive Cohort, which consists of 30,097 adults aged 45-85 years. Race/ethnicity was self-reported. Corneal-compensated intraocular pressure (IOP) was measured in mmHg using the Reichert Ocular Response Analyzer. Participants were asked to report if they have ever had a diagnosis of glaucoma and whether they used eye care in the past year. A glaucoma polygenic risk score (PRS) was calculated. Logistic and linear regression models were used. Results: Black individuals had higher mean IOP levels (beta coefficient (ß) = 1.46; 95% confidence interval [CI], 0.62, 2.30) while Chinese, Japanese and Korean (ß = -1.00; 95% CI, -1.63, -0.38) and Southeast Asian and Filipino individuals (ß = -1.56; 95% CI, -2.68, -0.43) had lower mean IOP levels as compared to White individuals after adjustment for sociodemographic, behavioral, genetic, and health-related variables. Black people were more likely to report glaucoma as compared to White people after adjustment (odds ratio [OR] = 2.43; 95% CI, 1.27, 4.64). Conclusion: Racial and ethnic differences in IOP and glaucoma were identified. Adjusting for sociodemographic, behavioral, genetic, and health-related variables did not fully explain these differences. Longitudinal research is needed to further explore the reasons for these differences and to understand their relevance to disease pathogenesis and progression.

The impact of fast food marketing on brand preferences and fast food intake of youth aged 10-17 across six countries.

BACKGROUND: Consumption of fast food, which is associated with poor diet, weight gain and the development of noncommunicable diseases, is high amongst youth. Fast food marketing, a modifiable determinant of excess weight and obesity, affects youth's food-related behaviours. This study aimed to examine the relationship between exposure to fast food marketing and the fast food brand preferences and intake amongst youth aged 10-17 across six countries. METHODS: Data from 9,695 youth respondents living in Australia, Canada, Chile, Mexico, the United Kingdom (UK) and the United States (US) were analyzed from the 2019 International Food Policy Study (IFPS) Youth Survey. Survey measures assessed exposure to fast food marketing and brand-specific marketing, and preference for these brands and fast food intake. Regression models adjusted for age, sex, income adequacy and ethnicity were used to examine the associations. RESULTS: Exposure to fast food marketing was positively associated with brand preferences and intake consistently across most countries. Overall, preference for McDonald's (OR:1.97; 95% CI:1.52, 2.56), KFC (OR:1.61; 95% CI:1.24, 2.09) and Subway (OR:1.73; 95% CI:1.34, 2.24) were highest when exposed to general fast food marketing ≥ 2x/week compared to never. Preference for McDonald's (OR:2.32; 95% CI:1.92, 2.79), KFC (OR:2.28; 95% CI:1.95, 2.68) and Subway (OR:2.75; 95% CI:2.32, 3.27) were also higher when exposed to marketing for each brand compared to not. Fast food intake was highest in Chile (IRR:1.90; 95% CI:1.45, 2.48), the UK (IRR:1.40; 95% CI:1.20, 1.63), Canada (IRR:1.32; 95% CI:1.19, 1.48), Mexico (IRR:1.26; 95% CI:1.05, 1.53) and the US (IRR:1.21; 95% CI:1.05, 1.41) when exposed to general fast food marketing ≥ 2x/week compared to never and was higher across most countries when exposed to brand-specific marketing compared to not. Respondents classified as ethnic minorities were more likely to report consuming fast food than ethnic majorities, and females were less likely to report consuming fast food than males. CONCLUSIONS: Exposure to fast food marketing is consistently and positively associated with brand preferences and fast food intake in all six countries. Our results highlight the need for strict government regulation to reduce exposure of unhealthy food marketing to youth in all six countries.

Alcohol Consumption, Genetic Risk, and Intraocular Pressure and Glaucoma: The Canadian Longitudinal Study on Aging.

Purpose: The purpose of this study was to examine the association of alcohol consumption with intraocular pressure (IOP) and glaucoma and to assess whether any associations are modified by a glaucoma polygenic risk score (PRS). Methods: Cross-sectional analysis of data from the Canadian Longitudinal Study on Aging Comprehensive Cohort, consisting of 30,097 adults ages 45 to 85 years, was done. Data were collected from 2012 to 2015. Alcohol consumption frequency (never, occasional, weekly, and daily) and type (red wine, white wine, beer, liquor, and other) were measured by an interviewer-administered questionnaire. Total alcohol intake (grams/week) was estimated. IOP was measured in mm Hg using the Reichert Ocular Response Analyzer. Participants reported a diagnosis of glaucoma from a doctor. Logistic and linear regression models were used to adjust for demographic, behavioral, and health variables. Results: Daily drinkers had higher IOP compared to those who never drank (ß = 0.45, 95% confidence interval (CI) = 0.05, 0.86). An increase in total weekly alcohol intake (per 5 drinks) was also associated with higher IOP (ß = 0.20, 95% CI = 0.15, 0.26). The association between total alcohol intake and IOP was stronger in those with a higher genetic risk of glaucoma (P for interaction term = 0.041). There were 1525 people who reported being diagnosed with glaucoma. Alcohol consumption frequency and total alcohol intake were not associated with glaucoma. Conclusions: Alcohol frequency and total alcohol intake were associated with elevated IOP but not with glaucoma. The PRS modified the association between total alcohol intake and IOP. Findings should be confirmed in longitudinal analyses.

GENLIB: new function to simulate haplotype transmission in large complex genealogies.

SUMMARY: Founder populations with deep genealogical data are well suited for investigating genetic variants contributing to diseases. Here, we present a major update of the genealogical analysis R package GENLIB, centered around a new function which can simulate the transmission of haplotypes from founders to probands along very large and complex user-specified genealogies. AVAILABILITY AND IMPLEMENTATION: The latest update of the GENLIB package (v1.1.9) contains the new gen.simuHaplo() function and is available on the CRAN repository and from https://github.com/R-GENLIB/GENLIB. Examples can be accessed at https://github.com/R-GENLIB/simuhaplo_functions.

Genome-wide association study of age at menarche in the Taiwan Biobank suggests NOL4 as a novel associated gene.

Sexual maturation is a complex physiological process that involves multiple variables, such as genetic and environmental factors. Among females, age at menarche (AM) is a critical milestone for sexual maturation. This study aimed to identify genetic markers of AM using nationwide population cohort data in Taiwan. Females with self-reported AM between 10 and 16 years (N = 39,827) were eligible for the final analysis. To identify genetic signals related to AM, we conducted a genome-wide association study using a linear regression model and split-half meta-analysis method to verify our findings. The Functional Mapping and Annotation web-based platform was used for positional mapping and gene-based and gene-set analyses. The meta-analysis identified four significant loci, i.e., LIN28B (pooled P = 1.39 × 10-21), NOL4 (pooled P = 8.94 × 10-9), GPR45 (pooled P = 4.19 × 10-11), and LOC105373831 (pooled P = 4.37 × 10-8), that were associated with AM. MAGMA gene-based analysis revealed that LIN28B (P = 1.13 × 10-8), NOL4 (P = 2.27 × 10-7), RXRG (P = 4.34 × 10-7), ETV5 (P = 1.75 × 10-6), and HACE1 (P = 1.82 × 10-6) were significantly associated with AM, while the gene-set analysis identified a significantly enriched pathway involving mTOR signaling complex (FDR corrected P = 1.28 × 10-2). The results replicated evidence for several genetic markers associated with AM in the Taiwanese female population. Our analysis identified a novel locus (rs7239368) in NOL4 associated with AM (ß = 0.051 ± 0.009 years, pooled P = 8.94 × 10-9), whereas additional research is needed to validate its molecular role in sexual maturation.

Inverse Association of APOE ε4 and Glaucoma Modified by Systemic Hypertension: The Canadian Longitudinal Study on Aging.

Purpose: Studies examining the apolipoprotein E (APOE) ε4 allele and glaucoma are inconsistent, which could be due to interactions with other factors. We examined the relationship between the APOE ε4 allele and glaucoma and intraocular pressure in a large, population-based random sample and explored whether the APOE ε4 allele interacted with systemic hypertension. Methods: Data came from the Canadian Longitudinal Study on Aging, a population-based study that included 24,655 adults ages 45 to 85 years old in the European ancestry cohort. APOE genotypes were derived from single-nucleotide polymorphisms rs429358 and rs7412. Participants were asked about a prior diagnosis of glaucoma from a doctor. Corneal compensated intraocular pressure (IOP) was measured using the Reichart Ocular Response Analyzer. Results: Having an APOE ε4 allele was associated with a lower odds of glaucoma after adjusting for age, sex, IOP, and the top 10 population structure principal components (odds ratio [OR] = 0.83; 95% confidence interval [CI], 0.69-0.98; P = 0.033). A novel statistically significant interaction was found in that having an APOE ε4 allele was only associated with glaucoma in those without systemic hypertension (OR = 0.62; 95% CI, 0.46-0.85) although it was not associated in those with it (OR = 0.97; 95% CI, 0.79-1.21) (interaction term P value = 0.017). APOE ε4 was not associated with IOP (ß = -0.01; 95% CI, -0.13 to 0.10). Conclusions: Evidence increasingly points to the APOE ε4 allele having protective benefits against glaucoma, but this association was limited to those without systemic hypertension. Further research is needed to understand the biological mechanisms for these findings and the treatment potential they hold.

Comparison of mixed model based approaches for correcting for population substructure with application to extreme phenotype sampling.

BACKGROUND: Mixed models are used to correct for confounding due to population stratification and hidden relatedness in genome-wide association studies. This class of models includes linear mixed models and generalized linear mixed models. Existing mixed model approaches to correct for population substructure have been previously investigated with both continuous and case-control response variables. However, they have not been investigated in the context of extreme phenotype sampling (EPS), where genetic covariates are only collected on samples having extreme response variable values. In this work, we compare the performance of existing binary trait mixed model approaches (GMMAT, LEAP and CARAT) on EPS data. Since linear mixed models are commonly used even with binary traits, we also evaluate the performance of a popular linear mixed model implementation (GEMMA). RESULTS: We used simulation studies to estimate the type I error rate and power of all approaches assuming a population with substructure. Our simulation results show that for a common candidate variant, both LEAP and GMMAT control the type I error rate while CARAT's rate remains inflated. We applied all methods to a real dataset from a Québec, Canada, case-control study that is known to have population substructure. We observe similar type I error control with the analysis on the Québec dataset. For rare variants, the false positive rate remains inflated even after correction with mixed model approaches. For methods that control the type I error rate, the estimated power is comparable. CONCLUSIONS: The methods compared in this study differ in their type I error control. Therefore, when data are from an EPS study, care should be taken to ensure that the models underlying the methodology are suitable to the sampling strategy and to the minor allele frequency of the candidate SNPs.

General and abdominal obesity trajectories across adulthood, and risk of prostate cancer: results from the PROtEuS study, Montreal, Canada.

PURPOSE: Greater body fatness is a probable cause of advanced prostate cancer (PCa). Body fat distribution and timing of exposure may be relevant. We investigated associations between body size trajectories and PCa incidence in a population-based case-control study in Montreal, Canada. METHODS: Cases (n = 1,931), aged ≤ 75 years, were diagnosed with PCa in 2005-2009; 1,994 controls were selected from the electoral list. Interviews were conducted to assess body mass index (BMI) and Stunkard's silhouette at ages 20, 40, 50, 60 years, and before interview. Current waist and hip circumferences were measured, and a predictive model estimated waist circumference in the past. BMI and waist circumference trajectories were determined to identify subgroups. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between anthropometric indicators and PCa. RESULTS: Subjects with a current BMI ≥ 30 kg/m2 had a lower risk of overall PCa (OR 0.71, 95% CI 0.59-0.85). Associations with adult BMI followed similar trends for less and more aggressive tumors, with stronger inverse relationships in early adulthood. Contrastingly, current waist circumference ≥ 102 cm was associated with elevated risk of high-grade PCa (OR 1.33, 95% CI 1.03-1.71). Men with increasing BMI or waist circumference adult trajectories had a lower risk of PCa, especially low-grade, than those in the normal-stable range. This was especially evident among men in the obese-increase group for BMI and waist circumference. CONCLUSION: Abdominal obesity increased the risk of aggressive PCa. The inverse relationship between body size trajectories and PCa may reflect PSA hemodilution, lower detection, and/or a true etiological effect.

Correspondence Between Genomic- and Genealogical/Coalescent-Based Inference of Homozygosity by Descent in Large French-Canadian Genealogies.

Research on the genetics of complex traits overwhelmingly focuses on the additive effects of genes. Yet, animal studies have shown that non-additive effects, in particular homozygosity effects, can shape complex traits. Recent investigations in human studies found some significant homozygosity effects. However, most human populations display restricted ranges of homozygosity by descent (HBD), making the identification of homozygosity effects challenging. Founder populations give rise to higher HBD levels. When deep genealogical data are available in a founder population, it is possible to gain information on the time to the most recent common ancestor (MRCA) from whom a chromosomal segment has been transmitted to both parents of an individual and in turn to that individual. This information on the time to MRCA can be combined with the time to MRCA inferred from coalescent models of gene genealogies. HBD can also be estimated from genomic data. The extent to which the genomic HBD measures correspond to the genealogical/coalescent measures has not been documented in founder populations with extensive genealogical data. In this study, we used simulations to relate genomic and genealogical/coalescent HBD measures. We based our simulations on genealogical data from two ongoing studies from the French-Canadian founder population displaying different levels of inbreeding. We simulated single-nucleotide polymorphisms (SNPs) in a 1-Mb genomic segment from a coalescent model in conjunction with the observed genealogical data. We compared genealogical/coalescent HBD to two genomic methods of HBD estimation based on hidden Markov models (HMMs). We found that genomic estimates of HBD correlated well with genealogical/coalescent HBD measures in both study genealogies. We described generation time to coalescence in terms of genomic HBD estimates and found a large variability in generation time captured by genomic HBD when considering each SNP. However, SNPs in longer segments were more likely to capture recent time to coalescence, as expected. Our study suggests that estimating the coalescent gene genealogy from the genomic data to use in conjunction with observed genealogical data could provide valuable information on HBD.

Clinical and demographic predictors of antiretroviral efficacy in HIV-HBV co-infected patients.

Background: The clinical and demographic characteristics that predict antiretroviral efficacy among patients co-infected with HIV and hepatitis B virus (HBV) remain poorly defined. We evaluated HIV virological suppression and rebound in a cohort of HIV-HBV co-infected patients initiated on antiretroviral therapy. Methods: A retrospective cohort analysis was performed with Canadian Observation Cohort Collaboration data. Cox proportional hazards models were used to determine the factors associated with time to virological suppression and time to virological rebound. Results: HBV status was available for 2,419 participants. A total of 8% were HBV co-infected, of whom 95% achieved virological suppression. After virological suppression, 29% of HIV-HBV co-infected participants experienced HIV virological rebound. HBV co-infection itself did not predict virological suppression or rebound risk. The rate of virological suppression was lower among patients with a history of injection drug use or baseline CD4 cell counts of <199 cells per cubic millimetre. Low baseline HIV RNA and men-who-have-sex-with-men status were significantly associated with a higher rate of virological suppression. Injection drug use and non-White race predicted viral rebound. Conclusions: HBV co-infected HIV patients achieve similar antiretroviral outcomes as those living with HIV mono-infection. Equitable treatment outcomes may be approached by targeting resources to key subpopulations living with HIV-HBV co-infection.

Historique: Les caractéristiques cliniques et démographiques prédictives de l'efficacité antirétrovirale chez les patients co-infectés par le virus de l'immunodéficience humaine (VIH) et le virus de l'hépatite B (VHB) demeurent mal définies. Les chercheurs ont évalué la suppression et le rebond virologiques du VIH dans une cohorte de patients co-infectés par le VIH et le VHB chez qui on avait entrepris un traitement antirétroviral. Méthodologie: Les chercheurs ont réalisé une analyse rétrospective de cohorte à l'aide des données de la Canadian Observation Cohort Collaboration. Ils ont utilisé le modèle à risques proportionnels de Cox pour déterminer les facteurs associés à la période jusqu'à la suppression et au rebond virologiques. Résultats: Les chercheurs ont obtenu le statut de VHB de 2 419 participants. Au total, 8 % étaient co-infectés par le VHB, dont 95 % présentaient une suppression virologique. Après la suppression virologique, 29 % des participants co-infectés par le VIH et le VHB ont subi un rebond virologique du VIH. En elle-même, la co-infection par le VHB n'était pas prédictive de la suppression virologique ou du risque de rebond. Le taux de suppression virologique était plus faible chez les patients ayant des antécédents de consommation de drogues injectables ou une numération des cellules CD4 de référence de moins de 199 cellules par millimètre cube. Un ARN du VIH de référence bas et les hommes ayant des relations sexuelles avec des hommes étaient associés de manière significative avec un taux plus élevé de suppression virologique. La consommation de drogues injectables et les races non blanches étaient prédictives d'un rebond viral. Conclusion: Les patients atteints du VHB co-infectés par le VIH obtenaient des résultats antirétroviraux semblables à ceux qui étaient seulement infectés par le VIH. On peut anticiper des résultats cliniques équitables des traitements en ciblant les ressources vers les sous-populations atteintes d'une co-infection par le VIH et le VHB.

Body shape and pants size as surrogate measures of obesity among males in epidemiologic studies.

This study aimed at characterizing anthropometric indicators that can be used as alternatives to measurements for assessing overall obesity over adulthood and abdominal obesity among men. We used data from a population-based case-control study of prostate cancer conducted in Montreal, Canada in 2005-2012. It included men aged ≤ 75 years, 1872 of which were newly diagnosed with prostate cancer, and 1918 others randomly selected from the electoral list. In-person interviews elicited reports of height as well as of weight, pants size and Stunkard's silhouette at 5 time points over adulthood, i.e., for the ages of 20, 40, 50 and 60 years, if applicable, and at the time of interview. Waist and hip circumferences were measured by interviewers following a validated protocol. Analyses were conducted on the overall sample of 3790 subjects, after having confirmed that results did not differ according to disease status. Stunkard's silhouette scale proved to be an easy-to-administer tool that reflects well reported body mass index, either recently or decades in the past among adult males. It was discriminatory enough to classify individuals according to commonly-used obesity categories. We observed that a model including age, reported pants size, silhouette and weight can reasonably predict current abdominal obesity. In conclusion, alternative anthropometric indicators can serve as valuable means to assess overall and abdominal obesity when measurements cannot be envisaged in the context of epidemiological studies.

Food and Beverage Advertising to Children and Adolescents on Television: A Baseline Study.

The progressive rise in Canadian child obesity has paralleled trends in unhealthy food consumption. Industry has contributed to these trends through aggressive food and beverage marketing in various media and child settings. This study aimed to assess the extent of food and beverage advertising on television in Canada and compare the frequency of food advertising broadcasted during programs targeted to preschoolers, children, adolescents and adults. Annual advertising from 2018 was drawn from publicly available television program logs. Food and beverage advertisement rates and frequencies were compared by, target age group, television station, month and food category, using linear regression modelling and chi-square tests, in SAS version 9.4. Rates of food and beverage advertising differed significantly between the four target age groups, and varied significantly by television station and time of the year, in 2018. The proportion of advertisements for food and beverage products was significantly greater during preschooler-, child-, and adult-programming [5432 (54%), 142,451 (74%) and 2,886,628 (48%), respectively; p < 0.0001] compared to adolescent-programming [27,268 (42%)]. The proportion of advertisements promoting fast food was significantly greater among adolescent-programming [33,475 (51%), p < 0.0001] compared to other age groups. Legislation restricting food and beverage advertising is needed in Canada as current self-regulatory practices are failing to protect young people from unhealthy food advertising and its potential negative health effects.

Age-Related Eye Disease and Cognitive Function: The Search for Mediators.

PURPOSE: Age-related eye disease may be associated with cognitive decline, but the scientific literature has not been consistent. Furthermore, no studies have been able to explain the relationship. Our objective was to assess whether older adults with age-related macular degeneration (AMD) or glaucoma performed worse on 6 cognitive tests compared with older adults with normal vision and, if so, to understand why. DESIGN: Cross-sectional analysis of hospital-based study (Maisonneuve-Rosemont Hospital Ophthalmology Clinics, Montréal, Canada). PARTICIPANTS: Three hundred thirty-six adults 65 years of age or older with either AMD, glaucoma, or normal vision. METHODS: Cognition was measured with 6 cognitive tests administered orally. Activity levels were measured using the Victoria Longitudinal Study Activity Lifestyle Questionnaire. Visual acuity and visual field were measured. Multiple linear regression was used. Mediation was assessed using structural equation modeling. MAIN OUTCOME MEASURES: Results of the verbal fluency test (animal and letter versions), the digit span test (forward and backward versions), and the logical memory test (immediate and delayed recall). RESULTS: People with glaucoma showed lower scores on 3 cognitive tests than the group with normal vision: the digit span forward and backward tests (ß = -0.8 [95% confidence interval (CI), -1.5 to -0.2] and ß = -0.7 [95% CI, -1.3 to -0.1], respectively) and the logical memory test with immediate recall (ß = -1.3 [95% CI, -2.4 to -0.2]). Activity levels statistically significantly mediated the relationship between glaucoma and the digit span forward test (P = 0.043; percentage of the total effect mediated, 17%). CONCLUSIONS: People with glaucoma showed lower scores on cognitive tests that may depend on verbal working memory and encoding. If confirmed in longitudinal studies, interventions should be developed that are appropriate for a visually impaired population to slow this cognitive decline.

Characteristics and outcomes of antiretroviral-treated HIV-HBV co-infected patients in Canada?

BACKGROUND: Hepatitis B (HBV) and Human Immunodeficiency Virus (HIV) share common risk factors for exposure. Co-infected patients have an increased liver-related mortality risk and may have accelerated HIV progression. The epidemiology and demographic characteristics of HIV-HBV co-infection in Canada remain poorly defined. We compared the demographic and clinical characteristics and factors associated with advanced hepatic fibrosis between HIV and HIV-HBV co-infected patients. METHODS: A retrospective cohort analysis was conducted using data from the Canadian Observational Cohort (CANOC) Collaboration, including eight sites from British Columbia, Quebec, and Ontario. Eligible participants were HIV-infected patients who initiated combination ARV between January 1, 2000 and December 14, 2014. Demographic and clinical characteristics were compared between HIV-HBV co-infected and HIV-infected groups using chi-square or Fisher exact tests for categorical variables, and Wilcoxon's Rank Sum test for continuous variables. Liver fibrosis was estimated by the AST to Platelet Ratio Index (APRI). RESULTS: HBV status and APRI values were available for 2419 cohort participants. 199 (8%) were HBV co-infected. Compared to HIV-infected participants, HIV-HBV co-infected participants were more likely to use injection drugs (28% vs. 21%, p = 0.03) and be HCV-positive (31%, vs. 23%, p = 0.02). HIV-HBV co-infected participants had lower baseline CD4 T cell counts (188 cells/mm3, IQR: 120-360) compared to 235 cells/mm3 in HIV-infected participants (IQR: 85-294) (p = 0.0002) and higher baseline median APRI scores (0.50 vs. 0.37, p < 0.0001). This difference in APRI was no longer clinically significant at follow-up (0.32 vs. 0.30, p = 0.03). HIV-HBV co-infected participants had a higher mortality rate compared to HIV-infected participants (11% vs. 7%, p = 0.02). CONCLUSION: The prevalence, demographic and clinical characteristics of the HIV-HBV co-infected population in Canada is described. HIV-HBV co-infected patients have higher mortality, more advanced CD4 T cell depletion, and liver fibrosis that improves in conjunction with ARV therapy. The high prevalence of unknown HBV status demonstrates a need for increased screening among HIV-infected patients in Canada.

Utilization of key preventive measures for pregnancy complications and malaria among women in Jimma Zone, Ethiopia.

BACKGROUND: In Ethiopia, malaria infections and other complications during pregnancy contribute to the high burden of maternal morbidity and mortality. Preventive measures are available, however little is known about the factors influencing the uptake of maternal health services and interventions by pregnant women in Ethiopia. METHODS: We analyzed data from a community-based cross-sectional survey conducted in 2016 in three rural districts of Jimma Zone, Ethiopia, with 3784 women who had a pregnancy outcome in the year preceding the survey. We used multivariable logistic regression models accounting for clustering to identify the determinants of antenatal care (ANC) attendance and insecticide-treated net (ITN) ownership and use, and the prevalence and predictors of malaria infection among pregnant women. RESULTS: Eighty-four percent of interviewed women reported receiving at least one ANC visit during their last pregnancy, while 47% reported attending four or more ANC visits. Common reasons for not attending ANC included women's lack of awareness of its importance (48%), distance to health facility (23%) and unavailability of transportation (14%). Important determinants of ANC attendance included higher education level and wealth status, woman's ability to make healthcare decisions, and pregnancy intendedness. An estimated 48% of women reported owning an ITN during their last pregnancy. Of these, 55% reported to have always slept under it during their last pregnancy. Analysis revealed that the odds of owning and using ITNs were respectively 2.07 (95% CI: 1.62-2.63) and 1.73 (95% CI: 1.32-2.27) times higher among women who attended at least one ANC visit. The self-reported prevalence of malaria infection during pregnancy was low (1.4%) across the three districts. We found that young, uneducated, and unemployed women presented higher odds of malaria infection during their last pregnancy. CONCLUSION: ANC and ITN uptake during pregnancy in Jimma Zone fall below the respective targets of 95 and 90% set in the Ethiopian Health Sector Transformation Plan for 2020, suggesting that more intensive programmatic efforts still need to be directed towards improving access to these health services. Reaching ANC non-users and ITN ownership and use as part of ANC services could be emphasized to address these gaps.

Investigating Gene-Gene and Gene-Environment Interactions in the Association Between Overnutrition and Obesity-Related Phenotypes.

Introduction: Animal studies suggested that NFKB1, IKBKB, and SOCS3 genes could be involved in the association between overnutrition and obesity. This study aims to investigate interactions involving these genes and macronutrient intakes affecting obesity-related phenotypes. Methods: We used a traditional statistical method, logistic regression, and compared it to alternative statistical method, multifactor dimensionality reduction (MDR) and penalized logistic regression (PLR), to better detect genes/environment interactions in the Toronto Nutrigenomics and Health Study (n = 1639) using dichotomized body mass index (BMI) and waist circumference as obesity-related phenotypes. Exposure variables included genotype on 54 single nucleotide polymorphisms (NFKB1: 18, IKBKB: 9, SOCS3: 27), macronutrient (carbohydrates, protein, fat) and alcohol intakes and ethno-cultural background. Results: After correction for multiple testing, no interaction was found using logistic regression. MDR identified interactions between SOCS3 rs6501199 and rs4969172, and IKBKB rs3747811 affecting BMI in the Caucasian population; SOCS3 rs6501199 and NFKB1 rs1609798 affecting WC in the Caucasian population; and SOCS3 rs4436839 and IKBKB rs3747811 affecting WC in the South Asian population. PLR found a main effect of SOCS3 rs12944581 on BMI among the South Asian population. Conclusion: While MDR and PLR had discordant results, some models support results from previous studies. These results emphasize the need to use alternative statistical methods to investigate high-order interactions and suggest that variants in the nutrient-responsive hypothalamic IKKB/NF-kB signaling pathway may be involved in obesity pathogenesis.

A quality assessment of Health Management Information System (HMIS) data for maternal and child health in Jimma Zone, Ethiopia.

Health management information system (HMIS) data are important for guiding the attainment of health targets in low- and middle-income countries. However, the quality of HMIS data is often poor. High-quality information is especially important for populations experiencing high burdens of disease and mortality, such as pregnant women, newborns, and children. The purpose of this study was to assess the quality of maternal and child health (MCH) data collected through the Ethiopian Ministry of Health's HMIS in three districts of Jimma Zone, Oromiya Region, Ethiopia over a 12-month period from July 2014 to June 2015. Considering data quality constructs from the World Health Organization's data quality report card, we appraised the completeness, timeliness, and internal consistency of eight key MCH indicators collected for all the primary health care units (PHCUs) located within three districts of Jimma Zone (Gomma, Kersa and Seka Chekorsa). We further evaluated the agreement between MCH service coverage estimates from the HMIS and estimates obtained from a population-based cross-sectional survey conducted with 3,784 women who were pregnant in the year preceding the survey, using Pearson correlation coefficients, intraclass correlation coefficients (ICC), and Bland-Altman plots. We found that the completeness and timeliness of facility reporting were highest in Gomma (75% and 70%, respectively) and lowest in Kersa (34% and 32%, respectively), and observed very few zero/missing values and moderate/extreme outliers for each MCH indicator. We found that the reporting of MCH indicators improved over time for all PHCUs, however the internal consistency between MCH indicators was low for several PHCUs. We found poor agreement between MCH estimates obtained from the HMIS and the survey, indicating that the HMIS may over-report the coverage of key MCH services, namely, antenatal care, skilled birth attendance and postnatal care. The quality of MCH data within the HMIS at the zonal level in Jimma, Ethiopia, could be improved to inform MCH research and programmatic efforts.

Modeling gene-environment interactions in longitudinal family studies: a comparison of methods and their application to the association between the IGF pathway and childhood obesity.

BACKGROUND: The interactive effect of the IGF pathway genes with the environment may contribute to childhood obesity. Such gene-environment interactions can take on complex forms. Detecting those relationships using longitudinal family studies requires simultaneously accounting for correlations within individuals and families. METHODS: We studied three methods for detecting interaction effects in longitudinal family studies. The twin model and the nonparametric partition-based score test utilized individual outcome averages, whereas the linear mixed model used all available longitudinal data points. Simulation experiments were performed to evaluate the methods' power to detect different gene-environment interaction relationships. These methods were applied to the Quebec Newborn Twin Study data to test for interaction effects between the IGF pathway genes (IGF-1, IGFALS) and environmental factors (physical activity, daycare attendance and sleep duration) on body mass index outcomes. RESULTS: For the simulated data, the twin model with the mean time summary statistic yielded good performance overall. Modelling an interaction as linear when the true model had a different relationship influenced power; for certain non-linear interactions, none of the three methods were effective. Our analysis of the IGF pathway genes showed suggestive association for the joint effect of IGF-1 variant at position 102,791,894 of chromosome 12 and physical activity. However, this association was not statistically significant after multiple testing correction. CONCLUSIONS: The analytical approaches considered in this study were not robust to different gene-environment interactions. Methodological innovations are needed to improve the current methods' performances for detecting non-linear interactions. More studies are needed in order to better understand the IGF pathway's role in childhood obesity development.

Factors associated with human West Nile virus infection in Ontario: a generalized linear mixed modelling approach.

BACKGROUND: West Nile Virus (WNV) is a mosquito-borne pathogen that has become established in North America. Risk for human infection varies geographically in accordance with climate and population factors. Though often asymptomatic, human WNV infection can cause febrile illness or, rarely, neurologic disease. WNV has become a public health concern in Canada since its introduction in 2001. METHODS: To identify predictors of human WNV incidence at the public health unit (PHU) level in Ontario, Canada, we combined data on environmental and population characteristics of PHUs with historical mosquito and human surveillance records from 2002 to 2013. We examined the associations between annual WNV incidence and monthly climate indices (e.g. minimum and maximum temperature, average precipitation), land cover (e.g. deciduous forest, water), population structure (e.g. age and sex composition) and the annual percentage of WNV-positive mosquito pools from 2002 to 2013. We then developed a generalized linear mixed model with a Poisson distribution adjusting for spatial autocorrelation and repeat measures. Further to this, to examine potential 'early season' predictors of WNV incidence in a given year, we developed a model based on winter and spring monthly climate indices. RESULTS: Several climate indices, including mean minimum temperature (o C) in February (RR = 1.58, CI: [1.42, 1.75]), and the annual percentage of WNV-positive mosquito pools (RR = 1.07, CI: [1.04, 1.11]) were significantly associated with human WNV incidence at the PHU level. Higher winter minimum temperatures were also strongly associated with annual WNV incidence in the 'early season' model (e.g. February minimum temperature (RR = 1.91, CI: [1.73, 2.12]). CONCLUSIONS: Our study demonstrates that early season temperature and precipitation indices, in addition to the percentage of WNV-positive mosquito pools in a given area, may assist in predicting the likelihood of a more severe human WNV season in southern regions of Ontario, where WNV epidemics occur sporadically.