Nutrition, Genetic Variation and Male Fertility

Infertility affects nearly 50 million couples worldwide, with 40−50% of cases having a male factor component. It is well established that nutritional status impacts reproductive development, health and function, although the exact mechanisms have not been fully elucidated. Genetic variation that affects nutrient metabolism may impact fertility through nutrigenetic mechanisms. This review summarizes current knowledge on the role of several dietary components (vitamins A, B12, C, D, E, folate, betaine, choline, calcium, iron, caffeine, fiber, sugar, dietary fat, and gluten) in male reproductive health. Evidence of gene-nutrient interactions and their potential effect on fertility is also examined. Understanding the relationship between genetic variation, nutrition and male fertility is key to developing personalized, DNA-based dietary recommendations to enhance the fertility of men who have difficulty conceiving

Patient and public involvement in pragmatic trials : online survey of corresponding authors of published trials

Acknowledgements The authors acknowledge Dr. Paxton Montgomery Moon, Alison Howie, Hayden Nix and Dr. Merrick Zwarenstein for their contributions to the data extraction. They also thank Drs. Bruno Giraudeau and Agnes Caille (University of Tours), Dr. Laura Hanson (University of North Carolina School of Medicine) and Dr. Jill Harrison (Brown University) for assistance with pilot testing of the survey questionnaire. Funding: This work was supported by the Canadian Institutes of Health Research through the Project Grant competition (competitive, peer-reviewed), award number PJT-153045, and the National Institute of Aging ( NIA) of the National Institutes of Health under Award Number U54AG063546, which funds NIA Imbedded Pragmatic Alzheimer’s Disease and Related Dementias Clinical Trials Collaboratory ( NIA IMPACT Collaboratory). The funders had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.Peer reviewedPublisher PD

Cow’s Milk Fat and Child Growth, Development and Nutrition

Background: Health Canada and the Canadian Paediatric Society suggest that children over age 2 years transition from whole (3.25%) to reduced fat (0.1-2%) milk in effort to lower dietary fat intake and reduce the risk of overweight and obesity. However, observational studies have demonstrated that higher milk fat intake is associated with lower child adiposity. The optimal milk fat for child growth, development and nutrition is unknown. Objectives: 1) Determine the relationship between milk fat and child adiposity among existing literature, 2) Understand parent and physician perspectives about milk fat for children, 3) Evaluate the relationship between milk fat and child zBMI among children aged 9 months-8 years in the TARGet Kids! cohort, and 4) Design and launch a randomized controlled trial (RCT) to determine the effect of recommendations for whole vs. reduced fat milk on zBMI among children aged 2-4 years. Methods: 1) A systematic review and meta-analysis was conducted, 2) A qualitative study which sought to understand current practice, attitudes and preferences about milk fat for children aged 2-5 years, 3) A prospective cohort study was conducted using linear mixed effects models, and 4) A RCT protocol (Cow’s Milk Fat Obesity pRevention Trial or CoMFORT) was developed to be embedded in TARGet Kids!. Results: Among 20,897 children aged 9 months-18 years, those who consumed whole milk had 0.61 (95% CI 0.52-0.72, pPh.D

Patient-reported outcomes and target effect sizes in pragmatic randomized trials in ClinicalTrials.gov: a cross-sectional analysis

Background Use of patient-reported outcomes (PROs) and patient and public engagement are critical ingredients of pragmatic trials, which are intended to be patient centered. Engagement of patients and members of the public in selecting the primary trial outcome and determining the target difference can better ensure that the trial is designed to inform the decisions of those who ultimately stand to benefit. However, to the best of our knowledge, the use and reporting of PROs and patient and public engagement in pragmatic trials have not been described. The objectives of this study were to review a sample of pragmatic trials to describe (1) the prevalence of reporting patient and public engagement; (2) the prevalence and types of PROs used; (3) how its use varies across trial characteristics; and (4) how sample sizes and target differences are determined for trials with primary PROs. Methods and findings This was a methodological review of primary reports of pragmatic trials. We used a published electronic search filter in MEDLINE to identify pragmatic trials, published in English between January 1, 2014 and April 3, 2019; we identified the subset that were registered in ClinicalTrials.gov and explicitly labeled as pragmatic. Trial descriptors were downloaded from ClinicalTrials.gov; information about PROs and sample size calculations were extracted from the manuscript. Chi-squared, Cochran–Armitage, and Wilcoxon rank sum tests were used to examine associations between trial characteristics and use of PROs. Among 4,337 identified primary trial reports, 1,988 were registered in CT.gov, of which 415 were explicitly labeled as pragmatic. Use of patient and public engagement was identified in 39 (9.4%). PROs were measured in 235 (56.6%): 144 (34.7%) used PROs as primary outcomes and 91 (21.9%) as only secondary outcomes. Primary PROs were symptoms (64; 44%), health behaviors (36; 25.0%), quality of life (17; 11.8%), functional status (16; 11.1%), and patient experience (10; 6.9%). Trial characteristics with lower prevalence of use of PROs included being conducted exclusively in children or adults over age 65 years, cluster randomization, recruitment in low- and middle-income countries, and primary purpose of prevention; trials conducted in Europe had the highest prevalence of PROs. For the 144 trials with a primary PRO, 117 (81.3%) reported a sample size calculation for that outcome; of these, 71 (60.7%) justified the choice of target difference, most commonly, using estimates from pilot studies (31; 26.5%), standardized effect sizes (20; 17.1%), or evidence reviews (16; 13.7%); patient or stakeholder opinions were used to justify the target difference in 8 (6.8%). Limitations of this study are the need for trials to be registered in ClinicalTrials.gov, which may have reduced generalizability, and extracting information only from the primary trial report. Conclusions In this study, we observed that pragmatic trials rarely report patient and public engagement and do not commonly use PROs as primary outcomes. When provided, target differences are often not justified and rarely informed by patients and stakeholders. Research funders, scientific journals, and institutions should support trialists to incorporate patient engagement to fulfill the mandate of pragmatic trials to be patient centered

Higher milk fat content is associated with higher 25-hydroxyvitamin D concentration in early childhood

Current guidelines for cow's milk consumption in children older than age 2 years suggest 1% or 2% milk to reduce the risk of obesity. Given that milk is the main dietary source of vitamin D for North American children and that vitamin D is fat soluble, we hypothesized 25-hydroxyvitamin D (25(OH)D) concentration to be positively associated with the fat content of milk. The objective was to determine the relationship between the fat content of milk consumed and the serum 25(OH)D concentration; our secondary objective was to explore the role that the volume of milk consumed played in this relationship. We completed a cross-sectional study of children aged 12-72 months in the TARGetKids! research network. Multivariable linear regression was used to test the association between milk fat content and child 25(OH)D, adjusted for clinically relevant covariates. The interaction between volume of milk and fat content was examined. Two thousand eight hundred fifty-seven children were included in the analysis. The fat content of milk was positively associated with 25(OH)D (p = 0.03), and the interaction between the volume of milk consumed and the milk fat content was statistically significant (p = 0.005). Children who drank 1% milk needed 2.46 cups (95% confidence interval (CI) 2.38-2.54) of milk to have a 25(OH)D concentration similar to that of children who drank 1 cup of homogenized milk (3.25% fat). Children who consumed 1% milk had 2.05 (95% CI 1.73-2.42) times higher odds of having a 25(OH)D concentration <50 nmol/L compared with children who consumed homogenized milk. In conclusion, recommendations for children to drink lower-fat milk (1% or 2%) may compromise serum 25(OH)D levels and may require study to ensure optimal childhood health

Patient and family engagement in the development of core outcome sets for two rare chronic diseases in children

Background: Core outcome sets (COS) are lists of consensus-determined outcomes to be measured and reported in all clinical research studies within a disease area. While including patients and families in COS development to improve their relevance and applicability to patient values is key, there is limited literature documenting practical barriers and facilitators to successful patient engagement in COS development. In this paper, as researchers and patient partners, we provide a resource for COS developers to meaningfully and effectively engage patients and families. Main body: To establish a consensus-based COS for children with two inherited metabolic diseases (medium-chain acyl-CoA dehydrogenase deficiency and phenylketonuria), we conducted an evidence review, Delphi survey, and workshop. Two adult patient partner co-investigators co-developed the study protocol, co-designed strategies to address challenges with incorporating patient perspectives, and led all patient engagement activities, including communication with a group of family advisors. Seven adult family advisors received training about COS development and subsequently contributed to Delphi survey development, outcome definitions, the consensus workshop, and selection of outcome measurement instruments. Patient partner co-investigators and family advisors were essential to the successful design, conduct, and completion of the two COS. Patient partner co-investigators supported the understanding, inclusion and engagement of family advisors, and helped develop accessible tools to determine patient-oriented outcome measurement instruments. Patient partner co-investigators and family advisors collaborated with the study team to co-develop surveys, modify technical language, and recruit participants to the study. Together, we addressed challenges to patient engagement in COS development such as unfamiliarity with study methods, comprehensibility of materials and ongoing engagement, and power imbalances between team members. Conclusion: Our approach to patient and family engagement in COS development for two rare conditions for children was feasible and considered valuable by all study team members, including patients and family members, in improving the relevance of the deliverable to patients. This approach to patient engagement in developing COS can be applied to other paediatric disease contexts, allowing patient and family perspectives to influence the direction of future studies to develop COS.Medicine, Faculty ofNon UBCPediatrics, Department ofReviewedFacultyResearche

The Impact of Migration on the Gut Metagenome of South Asian Canadians

South Asian (SA) Canadian immigrants have a higher risk of developing certain immune-mediated inflammatory diseases compared to non-migrant SAs. We sought to investigate the effect of migration on the gut metagenome and to identify microbiological associations between migration and conditions that may influence the development of immune-mediated inflammatory diseases. Metagenomic analysis of 58 first-generation (GEN1) SA immigrants and 38 unrelated Canadian born children-of-immigrants (GEN2) determined that the time lived in Canada was associated with continued changes in gut microbial communities. Migration of GEN1 to Canada early in life results in a gut community with similarities to GEN2 SA Canadians and non-SA North Americans. Conversely, GEN1 immigrants who arrived recently to Canada exhibited pronounced differences from GEN2, while displaying microbial similarities to a non-migrating SA cohort. Multivariate analysis identified that community composition was primarily influenced by high abundance taxa. Prevotella copri dominated in GEN1 and non-migrant SAs. Clostridia and functionally related Bacteroidia spp. replaced P. copri dominance over generations in Canada. Mutually exclusive Dialister species occurred at differing relative abundances over time and generations in Canada. This shift in species composition is accompanied by a change in genes associated with carbohydrate utilization and short-chain fatty acid production. Total energy derived from carbohydrates compared to protein consumption was significantly higher for GEN1 recent immigrants, which may influence the functional requirements of the gut community. This study demonstrates the associations between migration and the gut microbiome, which may be further associated with the altered risk of immune-mediated inflammatory diseases observed for SA Canadians