Grilling the data: application of specification curve analysis to red meat and all-cause mortality.

OBJECTIVES: To present an application of specification curve analysis-a novel analytic method that involves defining and implementing all plausible and valid analytic approaches for addressing a research question-to nutritional epidemiology. STUDY DESIGN AND SETTING: We reviewed all observational studies addressing the effect of red meat on all-cause mortality, sourced from a published systematic review, and documented variations in analytic methods (eg, choice of model, covariates, etc.). We enumerated all defensible combinations of analytic choices to produce a comprehensive list of all the ways in which the data may reasonably be analyzed. We applied specification curve analysis to data from National Health and Nutrition Examination Survey 2007 to 2014 to investigate the effect of unprocessed red meat on all-cause mortality. The specification curve analysis used a random sample of all reasonable analytic specifications we sourced from primary studies. RESULTS: Among 15 publications reporting on 24 cohorts included in the systematic review on red meat and all-cause mortality, we identified 70 unique analytic methods, each including different analytic models, covariates, and operationalizations of red meat (eg, continuous vs quantiles). We applied specification curve analysis to National Health and Nutrition Examination Survey, including 10,661 participants. Our specification curve analysis included 1208 unique analytic specifications, of which 435 (36.0%) yielded a hazard ratio equal to or more than 1 for the effect of red meat on all-cause mortality and 773 (64.0%) less than 1. The specification curve analysis yielded a median hazard ratio of 0.94 (interquartile range: 0.83-1.05). Forty-eight specifications (3.97%) were statistically significant, 40 of which indicated unprocessed red meat to reduce all-cause mortality and eight of which indicated red meat to increase mortality. CONCLUSION: We show that the application of specification curve analysis to nutritional epidemiology is feasible and presents an innovative solution to analytic flexibility.

Understanding Newcomer Challenges and Opportunities to Accessing Nature and Greenspace in Riverdale, Hamilton, Ontario: A Neighborhood-Centered Photovoice Study.

BACKGROUND: Access to and engagement with greenspace is related to improved health benefits. We sought to collaborate with community members as partners in research and co-creators in knowledge to better understand which components within a newcomer-dense community help or hinder individual and community efforts to access greenspace and nature-based activities. METHODS: We used photovoice methodology to engage with local residents in focus groups, photowalks, and photo-elicitation interviews. Themes were developed using direct content analysis. RESULTS: A total of 39 participants (ages 11-70 years; median years in Canada of 3.25 years) were engaged in this program of research. From the analysis, we developed four themes: (a) peace and beauty; (b) memories of home; (c) safety and cleanliness; and (d) welcoming strengthened and new opportunities. Participants associated nature with peace, citing it as "under-rated" but "vital" to the neighborhood. Via photographs and stories, participants also shared a multitude of safety concerns that prevent their access to green/outdoor spaces for healthy active living programs or activities (e.g., woodchip-covered playgrounds, ample amounts of garbage littering the park and school grounds, lack of timely ice removal on sidewalks, limited safe biking paths, and unsafe motor vehicle practices at the crosswalks surrounding local parks). CONCLUSION: To translate the key ideas and themes into an informed discussion with policy and decision-makers, we held an in-person exhibition and guided tour where community members, the lead photovoice researcher, and SCORE! principal investigator shared information about each theme in the form of a pseudo-narrative peppered with prepared discussion questions.

The effects of inulin-type fructans on cardiovascular disease risk factors: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Inulin-type fructans (ITF) are the leading prebiotics in the market. Available evidence provides conflicting results regarding the beneficial effects of ITF on cardiovascular disease risk factors. OBJECTIVES: This study aimed to evaluate the effects of ITF supplementation on cardiovascular disease risk factors in adults. METHODS: We searched MEDLINE, EMBASE, Emcare, AMED, CINAHL, and the Cochrane Library databases from inception through May 15, 2022. Eligible randomized controlled trials (RCTs) administered ITF or placebo (for example, control, foods, diets) to adults for ≥2 weeks and reported one or more of the following: low, very-low, or high-density lipoprotein cholesterol (LDL-C, VLDL-C, HDL-C); total cholesterol; apolipoprotein A1 or B; triglycerides; fasting blood glucose; body mass index; body weight; waist circumference; waist-to-hip ratio; systolic or diastolic blood pressure; or hemoglobin A1c. Two reviewers independently and in duplicate screened studies, extracted data, and assessed risk of bias. We pooled data using random-effects model, and assessed the certainty of evidence (CoE) using the Grading of Recommendations, Assessment, Development and Evaluation approach. RESULTS: We identified 1767 studies and included 55 RCTs with 2518 participants in meta-analyses. The pooled estimate showed that ITF supplementation reduced LDL-C [mean difference (MD) -0.14 mmol/L, 95% confidence interval (95% CI: -0.24, -0.05), 38 RCTs, 1879 participants, very low CoE], triglycerides (MD -0.06 mmol/L, 95% CI: -0.12, -0.01, 40 RCTs, 1732 participants, low CoE), and body weight (MD -0.97 kg, 95% CI: -1.28, -0.66, 36 RCTs, 1672 participants, low CoE) but little to no significant effect on other cardiovascular disease risk factors. The effects were larger when study duration was ≥6 weeks and in pre-obese and obese participants. CONCLUSION: ITF may reduce low-density lipoprotein, triglycerides, and body weight. However, due to low to very low CoE, further well-designed and executed trials are needed to confirm these effects. PROSPERO REGISTRATION NUMBER: CRD42019136745.

Physical Activity, Heart Rate Variability, and Ventricular Arrhythmia During the COVID-19 Lockdown: Retrospective Cohort Study.

BACKGROUND: Ventricular arrhythmias (VAs) increase with stress and national disasters. Prior research has reported that VA did not increase during the onset of the COVID-19 lockdown in March 2020, and the mechanism for this is unknown. OBJECTIVE: This study aimed to report the presence of VA and changes in 2 factors associated with VA (physical activity and heart rate variability [HRV]) at the onset of COVID-19 lockdown measures in Ontario, Canada. METHODS: Patients with implantable cardioverter defibrillator (ICD) followed at a regional cardiac center in Ontario, Canada with data available for both HRV and physical activity between March 1 and 31, 2020, were included. HRV, physical activity, and the presence of VA were determined during the pre- (March 1-10, 2020) and immediate postlockdown (March 11-31) period. When available, these data were determined for the same period in 2019. RESULTS: In total, 68 patients had complete data for 2020, and 40 patients had complete data for 2019. Three (7.5%) patients had VA in March 2019, whereas none had VA in March 2020 (P=.048). Physical activity was reduced during the postlockdown period (mean 2.3, SD 1.6 hours vs mean 2.1, SD 1.6 hours; P=.003). HRV was unchanged during the pre- and postlockdown period (mean 91, SD 30 ms vs mean 92, SD 28 ms; P=.84). CONCLUSIONS: VA was infrequent during the COVID-19 pandemic. A reduction in physical activity with lockdown maneuvers may explain this observation.

Effects of ambient air pollution on obesity and ectopic fat deposition: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Globally, the prevalence of obesity tripled from 1975 to 2016. There is evidence that air pollution may contribute to the obesity epidemic through an increase in oxidative stress and inflammation of adipose tissue. However, the impact of air pollution on body weight at a population level remains inconclusive. This systematic review and meta-analysis will estimate the association of ambient air pollution with obesity, distribution of ectopic adipose tissue, and the incidence and prevalence of non-alcoholic fatty liver disease among adults. METHODS AND ANALYSIS: The study will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for conduct and reporting. The search will include the following databases: Ovid Medline, Embase, PubMed, Web of Science and Latin America and the Caribbean Literature on Health Sciences, and will be supplemented by a grey literature search. Each article will be independently screened by two reviewers, and relevant data will be extracted independently and in duplicate. Study-specific estimates of associations and their 95% Confidence Intervals will be pooled using a DerSimonian and Laird random-effects model, implemented using the RevMan software. The I2 statistic will be used to assess interstudy heterogeneity. The confidence in the body of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. ETHICS AND DISSEMINATION: As per institutional policy, ethical approval is not required for secondary data analysis. In addition to being published in a peer-reviewed journal and presented at conferences, the results of the meta-analysis will be shared with key stakeholders, health policymakers and healthcare professionals. PROSPERO REGISTRATION NUMBER: CRD42023423955.

Precision prognostics for cardiovascular disease in Type 2 diabetes: a systematic review and meta-analysis.

BACKGROUND: Precision medicine has the potential to improve cardiovascular disease (CVD) risk prediction in individuals with Type 2 diabetes (T2D). METHODS: We conducted a systematic review and meta-analysis of longitudinal studies to identify potentially novel prognostic factors that may improve CVD risk prediction in T2D. Out of 9380 studies identified, 416 studies met inclusion criteria. Outcomes were reported for 321 biomarker studies, 48 genetic marker studies, and 47 risk score/model studies. RESULTS: Out of all evaluated biomarkers, only 13 showed improvement in prediction performance. Results of pooled meta-analyses, non-pooled analyses, and assessments of improvement in prediction performance and risk of bias, yielded the highest predictive utility for N-terminal pro b-type natriuretic peptide (NT-proBNP) (high-evidence), troponin-T (TnT) (moderate-evidence), triglyceride-glucose (TyG) index (moderate-evidence), Genetic Risk Score for Coronary Heart Disease (GRS-CHD) (moderate-evidence); moderate predictive utility for coronary computed tomography angiography (low-evidence), single-photon emission computed tomography (low-evidence), pulse wave velocity (moderate-evidence); and low predictive utility for C-reactive protein (moderate-evidence), coronary artery calcium score (low-evidence), galectin-3 (low-evidence), troponin-I (low-evidence), carotid plaque (low-evidence), and growth differentiation factor-15 (low-evidence). Risk scores showed modest discrimination, with lower performance in populations different from the original development cohort. CONCLUSIONS: Despite high interest in this topic, very few studies conducted rigorous analyses to demonstrate incremental predictive utility beyond established CVD risk factors for T2D. The most promising markers identified were NT-proBNP, TnT, TyG and GRS-CHD, with the highest strength of evidence for NT-proBNP. Further research is needed to determine their clinical utility in risk stratification and management of CVD in T2D.

People living with type 2 diabetes (T2D) are more likely to develop problems with their heart or blood circulation, known as cardiovascular disease (CVD), than people who do not have T2D. However, it can be difficult to predict which people with T2D are most likely to develop CVD. This is because current approaches, such as blood tests, do not identify all people with T2D who are at an increased risk of CVD. In this study we reviewed published papers that investigated the differences between people with T2D who experienced CVD compared to those who did not. We found some indicators that could potentially be used to determine which people with T2D are most likely to develop CVD. More studies are needed to determine how useful these are. However, they could potentially be used to enable clinicians to provide targeted advice and treatment to those people with T2D at most risk of developing CVD.

Twenty years of participation of racialised groups in type 2 diabetes randomised clinical trials: a meta-epidemiological review.

AIMS/HYPOTHESIS: Type 2 diabetes mellitus prevalence is increasing globally and the greatest burden is borne by racialised people. However, there are concerns that the enrolment of racialised people into RCTs is limited, resulting in a lack of ethnic and racial diversity. This may differ depending whether an RCT is government funded or industry funded. The aim of this study was to review the proportions of racialised and white participants included in large RCTs of type 2 diabetes pharmacotherapies relative to the disease burden of type 2 diabetes in these groups. METHODS: The Ovid MEDLINE database was searched from 1 January 2000 to 31 December 2020. English language reports of RCTs of type 2 diabetes pharmacotherapies published in select medical journals were included. Studies were included in this review if they had a sample size of at least 100 participants and all participants were adults with type 2 diabetes. Industry-funded trials must have recruited participants from at least two countries. Government-funded trials were not held to the same standard because they are typically conducted in a single country. Data including the numbers and proportions of participants by ethnicity and race were extracted from trial reports. The participation-to-prevalence ratio (PPR) was calculated for each trial by dividing the percentage of white and racialised participants in each trial by the percentage of white and racialised participants with type 2 diabetes, respectively, for the regions of recruitment. A random-effects meta-analysis was used to generate the pooled PPRs and 95% CIs across study types. A PPR <0.80 indicates under-representation and a PPR >1.20 indicates over-representation. Risk of bias assessments were not conducted for this study as the objective was to examine recruitment of racialised and white participants rather than evaluate the trustworthiness of clinical trial outcomes. RESULTS: A total of 83 trials were included, involving 283,122 participants, of which 15 were government-funded and 68 were industry-funded trials. In government-funded trials, the PPR for white participants was 1.11 (95% CI 0.99, 1.24) and the PPR for racialised participants was 0.72 (95% CI 0.60, 0.86). In industry-funded trials, the PPR for white participants was 1.95 (95% CI 1.74, 2.18) and the PPR for racialised participants was 0.36 (95% CI 0.32, 0.42). The limitations of this study include the reliance on investigator-reported ethnicity and race to classify participants as 'white' or 'racialised', the use of estimates for type 2 diabetes prevalence and demographic data, and the high levels of heterogeneity of pooled estimates. However, despite these limitations, the results were consistent with respect to direction. CONCLUSIONS/INTERPRETATION: Racialised participants are under-represented in government- and industry-funded type 2 diabetes trials. Strategies to improve recruitment and enrolment of racialised participants into RCTs should be developed. REGISTRATION: Open Science Framework registration no. f59mk ( https://osf.io/f59mk ) FUNDING: The authors received no financial support for this research or authorship of the article.

Assessment of reporting quality of randomized controlled trials investigating the effects of inulin-type fructans supplementation on cardiovascular disease risk factors: A systematic survey.

BACKGROUND: Transparent and detailed reporting of randomized controlled trials (RCTs) is essential to judge its validity and generalizability. We assessed the reporting quality of RCTs examining the effects of inulin-type fructans supplementation on cardiovascular risk factors, before and after the publication of the Consolidated Standards of Reporting Trials (CONSORT) in 2010. METHODS: We searched MEDLINE, EMBASE, Emcare, AMED, the Cochrane Library, and CINAHL from inception to May 15, 2022, including the reference lists of selected RCTs. We screened titles and abstracts and extracted the data independently and in duplicate. We included RCTs that investigated the effects of inulin-type fructans on cardiovascular disease risk factors (e.g., low-density lipoprotein cholesterol, triglycerides, fasting blood glucose) in adults (18 years or older). The primary outcomes of this study were: the overall reporting quality of RCTs (defined as the total number of items [0 to 36] present from the CONSORT checklist) published before and after CONSORT; and the study characteristics (e.g., sample size, significance of primary outcome) predictive of the CONSORT score. The secondary outcome was the reporting of each specific item of the CONSORT checklist during pre- and post-CONSORT periods. The mean difference in the total number of reported items in studies published before and after CONSORT were compared using a t-test and Poisson regression to explore the factors associated with overall reporting quality of RCTs. We used Fisher's exact test to compare the adherence to each of the 36 items during pre- and post-CONSORT periods. RESULTS: We identified 1,767 citations from our systematic search, of which 55 were eligible. There was a significant increase in the reporting of CONSORT items (mean difference 8.5, 95% confidence interval [CI] 5.24 to 11.71) between studies published before and after publication of CONSORT. The sole variable that was predictive of better reporting quality of RCTs was whether the study was published before or after CONSORT (incidence rate ratio 1.67, 95% CI 1.40 to 2.02). Completeness of reporting of RCTs only improved in 15 out of 36 items (41.6%) after the publication of CONSORT. CONCLUSION: The completeness of reporting in RCTs investigating inulin-type fructans supplementation on cardiovascular disease risk factors remains inadequate after the publication of CONSORT. Greater adherence to CONSORT by authors and enforcement of CONSORT by journals may improve the quality of reporting among RCTs.

Overprescription of antibiotics for treating hospitalized COVID-19 patients: A systematic review & meta-analysis.

Background: Empirical use of antibiotics was reported throughout the coronavirus disease of 2019 (COVID-19) pandemic; however, evidence of bacterial coinfection or secondary bacterial infection among COVID-19 patients was sparse. Antibiotic overprescription for COVID-19 patients without confirmed bacterial coinfection can increase antimicrobial resistance (AMR). The objective of this study is to assess the appropriateness of antibiotic use during COVID-19 by summarizing the frequency of antibiotic use among hospitalized COVID-19 and the frequency of antibiotic use in patients with COVID-19. Methods: A systematic search was conducted of the Embase, Medline, Web of Science, and Cochrane Library databases by generating search terms using the concepts of "COVID-19," "Bacterial Coinfection," "Secondary bacterial infection," and "Antimicrobial resistance" to identify studies reporting antibiotic prescription for hospitalized COVID-19 patients with or without bacterial coinfection. We excluded studies on outpatients, studies informed infection due to mechanical ventilation, and randomized controlled trials. The pooled estimate of the percentage of the total and confirmed appropriate antibiotic prescriptions provided to hospitalized COVID-19 patients was generated using a random effect meta-analysis with inverse variance weighting. The study protocol registration DOI is osf.io/d3fpm. Results: Of 157,623 participants from 29 studies (11 countries, 45 % women) included in our review, antibiotics were prescribed to 67 % of participants (CI 64 %-71 %, P < 0·001), of which 80 % (CI 76 %-83 %, P < 0·001) of prescriptions were for COVID-19 patients without confirmed bacterial coinfections. Antibiotic overprescription varied during different periods of the pandemic and between High-Income and Upper and Lower Middle-Income Countries. We found heterogeneity among the studies (I2 = 100 %). The risk of bias analysis showed that 100 % of the included studies had the proper sample framing, and we are at low risk of bias due to sampling. Discussion: We find greater than expected use of antibiotics to treat hospitalized COVID-19 patients without bacterial coinfections, which may contribute to AMR globally. Concrete guidelines for using antibiotics to treat COVID-19 patients, strict monitoring, and administering Antimicrobial Stewardship are needed to prevent overprescription.

Late preterm birth and growth trajectories during childhood: a linked retrospective cohort study.

BACKGROUND: Evidence suggests that accelerated postnatal growth in children is detrimental for adult cardiovascular health. It is unclear whether children born late preterm (34-36 weeks) compared to full term (≥ 39 weeks), have different growth trajectories. Our objective was to evaluate the association between gestational age groups and growth trajectories of children born between 2006-2014 and followed to 2021 in Ontario, Canada. METHODS: We conducted a retrospective cohort study of children from singleton births in TARGet Kids! primary care network with repeated measures of weight and height/length from birth to 14 years, who were linked to health administrative databases. Piecewise linear mixed models were used to model weight (kg/month) and height (cm/month) trajectories with knots at 3, 12, and 84 months. Analyses were conducted based on chronological age. RESULTS: There were 4423 children included with a mean of 11 weight and height measures per child. The mean age at the last visit was 5.9 years (Standard Deviation: 3.1). Generally, the more preterm, the lower the mean value of weight and height until early adolescence. Differences in mean weight and height for very/moderate preterm and late preterm compared to full term were evident until 12 months of age. Weight trajectories were similar between children born late preterm and full term with small differences from 84-168 months (mean difference (MD) -0.04 kg/month, 95% CI -0.06, -0.03). Children born late preterm had faster height gain from 0-3 months (MD 0.70 cm/month, 95% CI 0.42, 0.97) and 3-12 months (MD 0.17 cm/month, 95% CI 0.11, 0.22). CONCLUSIONS: Compared to full term, children born late preterm had lower average weight and height from birth to 14 years, had a slightly slower rate of weight gain after 84 months and a faster rate of height gain from 0-12 months. Follow-up is needed to determine if growth differences are associated with long-term disease risk.

Strengthening Community Roots: Anchoring Newcomers in Wellness and Sustainability (SCORE!): A protocol for the co-design and evaluation of a healthy active living program among a newcomer community in Canada.

BACKGROUND: The burden of childhood obesity and cardiometabolic risk factors affecting newcomer Canadians living in lower socioeconomic circumstances is a concerning public health issue. This paper describes Strengthening Community Roots: Anchoring Newcomers in Wellness and Sustainability (SCORE!), an academic-community research partnership to co-design interventions that nurture and optimize healthy activity living (HAL) among a community of children and families new to Canada in Hamilton, Ontario, Canada. METHODS/DESIGN: Our overarching program is informed by a socio-ecological model, and will co-create HAL interventions for children and families new to Canada rooted in outdoor, nature-based physical activity. We will proceed in three phases: Phase 1) synthesis of existing evidence regarding nature based HAL interventions among children and families; Phase 2) program development through four data collection activities including: i) community engagement activities to build trustful relationships and understand barriers and facilitators, including establishing a community advisory and action board, qualitative studies including a photovoice study, and co-design workshops to develop programs; ii) characterizing the demographics of the community through a household survey; iii) characterizing the built environment and HAL programs/services available in the community by developing an accessible real-time systems map; and iv) reviewing municipal policies relevant to HAL and sustainability; leading to Phase 3) implementation and evaluation of the feasibility of co-designed HAL programs. CONCLUSION: The etiology of childhood obesity and related chronic diseases is complex and multifactorial, as are intervention strategies. The SCORE! program of research brings together partners including community members, service providers, academic researchers, and organizational leaders to build a multi-component intervention that promotes the health and wellness of newcomer children and families.

Postsecondary Students' Knowledge of and Adherence to the 2019 Canada's Food Guide: A Cross-sectional Pilot Survey.

Purpose: We conducted a pilot survey among young adults attending a suburban Canadian university to understand: (1) knowledge of the 2019 Canada's Food Guide (CFG); (2) self-reported food choices and eating habits; (3) perceived influence of the CFG on food choices and eating habits; and (4) suggestions to improve engagement with CFG.Methods: Students were recruited, through posts on social media platforms, to complete an online questionnaire between 7 March and 6 April 2020.Results: One-hundred and twenty-one (70% women) students responded. One-third (33%) of women and 8% of men reported consuming the recommended proportion of vegetables and fruits (i.e., 40%-60% of the plate) at their most recent meal (P = 0.001). Men were more likely to report overconsuming protein foods than women (58% vs 32%, P = 0.005). The perceived influence of the CFG on food choices and eating habits was low, with a mean score 2.2 ± 1.4 out of 7, with 7 indicating "highly influential." Over 92% of participants believed awareness of the CFG could be improved through social media platforms.Conclusions: Although half of the participants correctly answered all 8 questions that assessed knowledge of the CFG, there is an opportunity for dietitians and related health professionals to improve engagement with CFG.

Fructose-containing food sources and blood pressure: A systematic review and meta-analysis of controlled feeding trials.

Whether food source or energy mediates the effect of fructose-containing sugars on blood pressure (BP) is unclear. We conducted a systematic review and meta-analysis of the effect of different food sources of fructose-containing sugars at different levels of energy control on BP. We searched MEDLINE, Embase and the Cochrane Library through June 2021 for controlled trials ≥7-days. We prespecified 4 trial designs: substitution (energy matched substitution of sugars); addition (excess energy from sugars added); subtraction (excess energy from sugars subtracted); and ad libitum (energy from sugars freely replaced). Outcomes were systolic and diastolic BP. Independent reviewers extracted data. GRADE assessed the certainty of evidence. We included 93 reports (147 trial comparisons, N = 5,213) assessing 12 different food sources across 4 energy control levels in adults with and without hypertension or at risk for hypertension. Total fructose-containing sugars had no effect in substitution, subtraction, or ad libitum trials but decreased systolic and diastolic BP in addition trials (P<0.05). There was evidence of interaction/influence by food source: fruit and 100% fruit juice decreased and mixed sources (with sugar-sweetened beverages [SSBs]) increased BP in addition trials and the removal of SSBs (linear dose response gradient) and mixed sources (with SSBs) decreased BP in subtraction trials. The certainty of evidence was generally moderate. Food source and energy control appear to mediate the effect of fructose-containing sugars on BP. The evidence provides a good indication that fruit and 100% fruit juice at low doses (up to or less than the public health threshold of ~10% E) lead to small, but important reductions in BP, while the addition of excess energy of mixed sources (with SSBs) at high doses (up to 23%) leads to moderate increases and their removal or the removal of SSBs alone (up to ~20% E) leads to small, but important decreases in BP in adults with and without hypertension or at risk for hypertension. Trial registration: Clinicaltrials.gov: NCT02716870.

Integrative multiomics analysis of infant gut microbiome and serum metabolome reveals key molecular biomarkers of early onset childhood obesity.

Evidence supports a complex interplay of gut microbiome and host metabolism as regulators of obesity. The metabolic phenotype and microbial metabolism of host diet may also contribute to greater obesity risk in children early in life. This study aimed to identify features that discriminated overweight/obese from normal weight infants by integrating gut microbiome and serum metabolome profiles. This prospective analysis included 50 South Asian children living in Canada, selected from the SouTh Asian biRth cohorT (START). Serum metabolites were measured by multisegment injection-capillary electrophoresis-mass spectrometry and the relative abundance of bacterial 16S rRNA gene amplicon sequence variant was evaluated at 1 year. Cumulative body mass index (BMIAUC) and skinfold thickness (SSFAUC) scores were calculated from birth to 3 years as the total area under the growth curve (AUC). BMIAUC and/or SSFAUC >85th percentile was used to define overweight/obesity. Data Integration Analysis for Biomarker discovery using Latent cOmponent (DIABLO) was used to identify discriminant features associated with childhood overweight/obesity. The associations between identified features and anthropometric measures were examined using logistic regression. Circulating metabolites including glutamic acid, acetylcarnitine, carnitine, and threonine were positively, whereas γ-aminobutyric acid (GABA), symmetric dimethylarginine (SDMA), and asymmetric dimethylarginine (ADMA) were negatively associated with childhood overweight/obesity. The abundance of the Pseudobutyrivibrio and Lactobacillus genera were positively, and Clostridium sensu stricto 1 and Akkermansia were negatively associated with childhood overweight/obesity. Integrative analysis revealed that Akkermansia was positively whereas Lactobacillus was inversely correlated with GABA and SDMA, and Pseudobutyrivibrio was inversely correlated with GABA. This study provides insights into metabolic and microbial signatures which may regulate satiety, energy metabolism, inflammatory processes, and/or gut barrier function, and therefore, obesity trajectories in childhood. Understanding the functional capacity of these molecular features and potentially modifiable risk factors such as dietary exposures early in life may offer a novel approach for preventing childhood obesity.

A culturally tailored personaliseD nutrition intErvention in South ASIan women at risk of Gestational Diabetes Mellitus (DESI-GDM): a randomised controlled trial protocol.

INTRODUCTION: South Asians are more likely to develop gestational diabetes mellitus (GDM) than white Europeans. Diet and lifestyle modifications may prevent GDM and reduce undesirable outcomes in both the mother and offspring. Our study seeks to evaluate the effectiveness and participant acceptability of a culturally tailored, personalised nutrition intervention on the glucose area under the curve (AUC) after a 2-hour 75 g oral glucose tolerance test (OGTT) in pregnant women of South Asian ancestry with GDM risk factors. METHODS AND ANALYSIS: A total of 190 South Asian pregnant women with at least 2 of the following GDM risk factors-prepregnancy body mass index>23, age>29, poor-quality diet, family history of type 2 diabetes in a first-degree relative or GDM in a previous pregnancy will be enrolled during gestational weeks 12-18, and randomly assigned in a 1:1 ratio to: (1) usual care, plus weekly text messages to encourage walking and paper handouts or (2) a personalised nutrition plan developed and delivered by a culturally congruent dietitian and health coach; and FitBit to track steps. The intervention lasts 6-16 weeks, depending on week of recruitment. The primary outcome is the glucose AUC from a three-sample 75 g OGTT 24-28 weeks' gestation. The secondary outcome is GDM diagnosis, based on Born-in-Bradford criteria (fasting glucose>5.2 mmol/L or 2 hours post load>7.2 mmol/L). ETHICS AND DISSEMINATION: The study has been approved by the Hamilton Integrated Research Ethics Board (HiREB #10942). Findings will be disseminated among academics and policy-makers through scientific publications along with community-orientated strategies. TRIAL REGISTRATION NUMBER: NCT03607799.

Early sex-dependent differences in metabolic profiles of overweight and adiposity in young children: a cross-sectional analysis.

BACKGROUND: Childhood obesity is a global health concern and can lead to lifetime cardiometabolic disease. New advances in metabolomics can provide biochemical insights into the early development of obesity, so we aimed to characterize serum metabolites associated with overweight and adiposity in early childhood and to stratify associations by sex. METHODS: Nontargeted metabolite profiling was conducted in the Canadian CHILD birth cohort (discovery cohort) at age 5 years (n = 900) by multisegment injection-capillary electrophoresis-mass spectrometry. Clinical outcome was defined using novel combined measures of overweight (WHO-standardized body mass index ≥ 85th percentile) and/or adiposity (waist circumference ≥ 90th percentile). Associations between circulating metabolites and child overweight/adiposity (binary and continuous outcomes) were determined by multivariable linear and logistic regression, adjusting for covariates and false discovery rate, and by subsequent sex-stratified analysis. Replication was assessed in an independent replication cohort called FAMILY at age 5 years (n = 456). RESULTS: In the discovery cohort, each standard deviation (SD) increment of branched-chain and aromatic amino acids, glutamic acid, threonine, and oxoproline was associated with 20-28% increased odds of overweight/adiposity, whereas each SD increment of the glutamine/glutamic acid ratio was associated with 20% decreased odds. All associations were significant in females but not in males in sex-stratified analyses, except for oxoproline that was not significant in either subgroup. Similar outcomes were confirmed in the replication cohort, where associations of aromatic amino acids, leucine, glutamic acid, and the glutamine/glutamic acid ratio with childhood overweight/adiposity were independently replicated. CONCLUSIONS: Our findings show the utility of combining measures of both overweight and adiposity in young children. Childhood overweight/adiposity at age 5 years has a specific serum metabolic phenotype, with the profile being more prominent in females compared to males.

Perceptions of COVID-19 risk, vaccine access and confidence: a qualitative description of South Asians in Canada.

OBJECTIVES: In the first full year of the COVID-19 pandemic (2020), South Asians living in the Greater Toronto and Hamilton Area (GTHA) and Greater Vancouver area (GVA) experienced specific barriers to accessing SARS-CoV-2 testing and reliable health information. However, between June 2021 and February 2022, the proportion of people having received at least one COVID-19 vaccine dose was higher among this group (96%) than among individuals who were not visible minorities (93%). A better understanding of successful approaches and the challenges experienced by those who remain unvaccinated among this highly vaccinated group may improve public health outreach in subsequent waves of the current pandemic or for future pandemic planning. Using qualitative methods, we sought to explore the perceptions of COVID-19 risk, vaccine access, uptake and confidence among South Asians living in Canada. DESIGN: Semistructured interviews conducted with 25 participants analysed using thematic analysis. Throughout this process, we held frequent discussions with members of the study's advisory group to guide data collection (community engagement, recruitment and data analysis). SETTING: Communities of the GTHA and GVA with interviews conducted virtually over Zoom or telephone. PARTICIPANTS: 25 participants (15 from Ontario and 10 from British Columbia) were interviewed between July 2021 and January 2022. 10 individuals were community members, 9 were advocacy group leaders and 6 were public health staff. RESULTS: Access to and confidence in the COVID-19 vaccine was impacted by individual risk perceptions; sources of trusted information (ethnic and non-ethnic); impact of COVID-19 and the pandemic on individuals, families and society; and experiences with COVID-19 mandates and policies (including temporal and generational differences). Approaches that include community-level awareness and tailored outreach (language and cultural context) were considered successful. CONCLUSIONS: Understanding factors and developing strategies that build vaccine confidence and improve access can guide approaches that increase vaccine acceptance in the current and future pandemics.Visual abstract can be found at https://drive.google.com/file/d/1iXdnJj9ssc3hXCllZxP0QA9DhHH-7uwB/view.

Dietary intake and cardiovascular outcomes in patients with chronic vascular disease: insights from the COMPASS trial cohort.

AIMS: Patients with coronary artery disease (CAD) and patients with peripheral artery disease (PAD) are at risk for major adverse cardiovascular events (MACE) and major adverse limb events (MALE). There are limited data regarding dietary patterns and the risk of recurrent MACE and MALE in CAD and PAD patients. We aimed to identify dietary patterns associated with MACE and MALE in patients with CAD and/or PAD. METHODS AND RESULTS: We analysed data collected from patients enrolled into the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial, in which diet was assessed by a short food frequency questionnaire (FFQ) at baseline. Two dietary pattern scores, the modified Alternate Healthy Eating Index (mAHEI) and Mediterranean Diet Score (mMDS), were calculated. We tested the association between mAHEI and mMDS and the incidence of MACE and/or MALE. The mean mAHEI score was 23.0 ± 7.7 (out of 70) overall and was similar comparing CAD and PAD patients. The incidence of MACE or MALE was 6.3% in the lowest diet quality quartile (as assessed by mAHEI) compared with 4.2% in the highest quartile over 30 months. In the fully adjusted model, the hazard ratio of a low diet quality (Quartile 1) compared with the highest (Quartile 4) for MACE or MALE was 1.27 (95% CI: 1.08-1.49; P = 0.004, Q1 vs. Q4). This excess hazard was primarily driven by higher MACE in both the CAD and PAD cohorts. CONCLUSIONS: Poor diet quality as assessed by the mAHEI is independently associated with a higher risk of recurrent MACE and MALE in patients with chronic CAD and/or PAD.

There are limited data regarding dietary patterns and the risk of recurrent major adverse cardiovascular and limb complications in patients with coronary artery disease (CAD) and peripheral artery disease (PAD). We show thatA low-quality diet is associated with a higher risk of cardiovascular and limb-related complicationsThis elevated risk is driven by higher rates of heart attack, stroke, and cardiovascular death in patients with a low-quality diet.

The Relationship Between Diet, Gut Microbiota, and Serum Metabolome of South Asian Infants at 1 Year.

BACKGROUND: Diet is known to affect the gut microbiota and the serum metabolome in adults, but this has not been fully explored in infants. Infancy is an important developmental period that may influence a person's long-term health. Infant development can be affected by diet, which also interacts with the developing gut microbiota. OBJECTIVES: This study aimed to explore the associations between diet, the gut microbiota, and the serum metabolome of 1-y-old infants with the overarching goal of identifying serum biomarkers of diet and/or the gut microbiota. METHODS: We derived dietary patterns of 1-y-old infants (n = 182) participating in the Canadian South Asian Birth Cohort (START) study. We compared gut microbiota α-diversity and ß-diversity and taxa relative abundance from 16S rRNA gene profiles with dietary patterns (PERMANOVA, Envfit) and investigated diet-serum metabolite associations using a multivariate analysis (partial least squares-discriminant analysis) and univariate analysis (t test). We explored the effect of nondietary factors on diet-serum metabolite relationships by incorporating diet, the gut microbiota, and maternal, perinatal, and infant characteristics in a multivariable forward stepwise regression. We replicated this analysis in White European infants, from the CHILD Cohort Study (n = 81). RESULTS: A dietary pattern characterized by formula consumption and negatively associated with breastfeeding most strongly predicted variation in the gut microbiota (R2 = 0.109) and serum metabolome (R2 = 0.547). Breastfed participants showed higher abundance of microbes from the genera Bifidobacterium (3.29 log2-fold) and Lactobacillus (7.93 log2-fold) and higher median concentrations of the metabolites S-methylcysteine (1.38 µM) and tryptophan betaine (0.43 µM) than nonbreastfed participants. Formula consuming infants showed higher median concentrations of branched-chain/aromatic amino acids (average 48.3 µM) than non-formula-consuming infants. CONCLUSIONS: Formula consumption and breastfeeding most strongly predicted the serum metabolites of 1-y-old infants, even when the gut microbiota, solid food consumption, and other covariates were considered.

Important food sources of fructose-containing sugars and adiposity: A systematic review and meta-analysis of controlled feeding trials.

BACKGROUND: Sugar-sweetened beverages (SSBs) providing excess energy increase adiposity. The effect of other food sources of sugars at different energy control levels is unclear. OBJECTIVES: To determine the effect of food sources of fructose-containing sugars by energy control on adiposity. METHODS: In this systematic review and meta-analysis, MEDLINE, Embase, and Cochrane Library were searched through April 2022 for controlled trials ≥2 wk. We prespecified 4 trial designs by energy control: substitution (energy-matched replacement of sugars), addition (energy from sugars added), subtraction (energy from sugars subtracted), and ad libitum (energy from sugars freely replaced). Independent authors extracted data. The primary outcome was body weight. Secondary outcomes included other adiposity measures. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the certainty of evidence. RESULTS: We included 169 trials (255 trial comparisons, n = 10,357) assessing 14 food sources at 4 energy control levels over a median 12 wk. Total fructose-containing sugars increased body weight (MD: 0.28 kg; 95% CI: 0.06, 0.50 kg; PMD = 0.011) in addition trials and decreased body weight (MD: -0.96 kg; 95% CI: -1.78, -0.14 kg; PMD = 0.022) in subtraction trials with no effect in substitution or ad libitum trials. There was interaction/influence by food sources on body weight: substitution trials [fruits decreased; added nutritive sweeteners and mixed sources (with SSBs) increased]; addition trials [dried fruits, honey, fruits (≤10%E), and 100% fruit juice (≤10%E) decreased; SSBs, fruit drink, and mixed sources (with SSBs) increased]; subtraction trials [removal of mixed sources (with SSBs) decreased]; and ad libitum trials [mixed sources (with/without SSBs) increased]. GRADE scores were generally moderate. Results were similar across secondary outcomes. CONCLUSIONS: Energy control and food sources mediate the effect of fructose-containing sugars on adiposity. The evidence provides a good indication that excess energy from sugars (particularly SSBs at high doses ≥20%E or 100 g/d) increase adiposity, whereas their removal decrease adiposity. Most other food sources had no effect, with some showing decreases (particularly fruits at lower doses ≤10%E or 50 g/d). This trial was registered at clinicaltrials.gov as NCT02558920 (https://clinicaltrials.gov/ct2/show/NCT02558920).