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Objective: The effect of fructose on cardiometabolic risk in humans is controversial. We conducted a systematic review and meta-analysis of controlled feeding trials to clarify the effect of fructose on glycemic control in individuals with diabetes.Research Design and Methods: We searched MEDLINE, EMBASE, and the Cochrane Library (through 22 March 2012) for relevant trials lasting ≥7 days. Data were aggregated by the generic inverse variance method (random-effects models) and expressed as mean difference (MD) for fasting glucose and insulin and standardized MD (SMD) with 95% CI for glycated hemoglobin (HbA(1c)) and glycated albumin. Heterogeneity was assessed by the Cochran Q statistic and quantified by the I(2) statistic. Trial quality was assessed by the Heyland methodological quality score (MQS).Results: Eighteen trials (n = 209) met the eligibility criteria. Isocaloric exchange of fructose for carbohydrate reduced glycated blood proteins (SMD -0.25 [95% CI -0.46 to -0.04]; P = 0.02) with significant intertrial heterogeneity (I(2) = 63%; P = 0.001). This reduction is equivalent to a ~0.53% reduction in HbA(1c). Fructose consumption did not significantly affect fasting glucose or insulin. A priori subgroup analyses showed no evidence of effect modification on any end point.Conclusions: Isocaloric exchange of fructose for other carbohydrate improves long-term glycemic control, as assessed by glycated blood proteins, without affecting insulin in people with diabetes. Generalizability may be limited because most of the trials were <12 weeks and had relatively low MQS (<8). To confirm these findings, larger and longer fructose feeding trials assessing both possible glycemic benefit and adverse metabolic effects are required. [ABSTRACT FROM AUTHOR]

Concerns have been raised about the adverse effect of fructose on blood pressure. International dietary guidelines, however, have not addressed fructose intake directly. A systematic review and meta-analysis was conducted to assess the effect of fructose in isocaloric exchange for other carbohydrates on systolic, diastolic, and mean arterial blood pressures. Studies were identified using Medline, Embase, and Cochrane databases (through January 9, 2012). Human clinical trials of isocaloric oral fructose exchange for other carbohydrate sources for ≥7 days were included in the analysis. Data were pooled by the generic inverse variance method using random-effects models and expressed as mean differences with 95% CI. Heterogeneity was assessed by the Q-statistic and quantified by I(2). Study quality was assessed using the Heyland Methodological Quality Score. Thirteen isocaloric (n=352) and 2 hypercaloric (n=24) trials met the eligibility criteria. Overall, fructose intake in isocaloric exchange for other carbohydrates significantly decreased diastolic (mean difference: -1.54 [95% CI: -2.77 to -0.32]) and mean arterial pressure (mean difference: -1.16 [95% CI: -2.15 to -0.18]). There was no significant effect of fructose on systolic blood pressure (mean difference: -1.10 [95% CI: -2.46 to 0.44]). The hypercaloric fructose feeding trials found no significant overall mean arterial blood pressure effect of fructose in comparison with other carbohydrates. To confirm these results, longer and larger trials are needed. Contrary to previous concerns, we found that isocaloric substitution of fructose for other carbohydrates did not adversely affect blood pressure in humans. [ABSTRACT FROM AUTHOR]

BACKGROUND: The contribution of fructose consumption in Western diets to overweight and obesity in populations remains uncertain. PURPOSE: To review the effects of fructose on body weight in controlled feeding trials. DATA SOURCES: MEDLINE, EMBASE, CINAHL, and the Cochrane Library (through 18 November 2011). STUDY SELECTION: At least 3 reviewers identified controlled feeding trials lasting 7 or more days that compared the effect on body weight of free fructose and nonfructose carbohydrate in diets providing similar calories (isocaloric trials) or of diets supplemented with free fructose to provide excess energy and usual or control diets (hypercaloric trials). Trials evaluating high-fructose corn syrup (42% to 55% free fructose) were excluded. DATA EXTRACTION: The reviewers independently reviewed and extracted relevant data; disagreements were reconciled by consensus. The Heyland Methodological Quality Score was used to assess study quality. DATA SYNTHESIS: Thirty-one isocaloric trials (637 participants) and 10 hypercaloric trials (119 participants) were included; studies tended to be small (<15 participants), short (<12 weeks), and of low quality. Fructose had no overall effect on body weight in isocaloric trials (mean difference, -0.14 kg [95% CI, -0.37 to 0.10 kg] for fructose compared with nonfructose carbohydrate). High doses of fructose in hypercaloric trials (+104 to 250 g/d, +18% to 97% of total daily energy intake) lead to significant increases in weight (mean difference, 0.53 kg [CI, 0.26 to 0.79 kg] with fructose). LIMITATIONS: Most trials had methodological limitations and were of poor quality. The weight-increasing effect of fructose in hypercaloric trials may have been attributable to excess energy rather than fructose itself. CONCLUSION: Fructose does not seem to cause weight gain when it is substituted for other carbohydrates in diets providing similar calories. Free fructose at high doses that provided excess calories modestly increased body weight, an effect that may be due to the extra calories rather than the fructose. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research. (ClinicalTrials.gov registration number: NCT01363791). [ABSTRACT FROM AUTHOR]

Objective: Because of blood lipid concerns, diabetes associations discourage fructose at high intakes. To quantify the effect of fructose on blood lipids in diabetes, we conducted a systematic review and meta-analysis of experimental clinical trials investigating the effect of isocaloric fructose exchange for carbohydrate on triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol in type 1 and 2 diabetes.Research Design and Methods: We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Library for relevant trials of > or =7 days. Data were pooled by the generic inverse variance method and expressed as standardized mean differences with 95% CI. Heterogeneity was assessed by chi(2) tests and quantified by I(2). Meta-regression models identified dose threshold and independent predictors of effects.Results: Sixteen trials (236 subjects) met the eligibility criteria. Isocaloric fructose exchange for carbohydrate raised triglycerides and lowered total cholesterol under specific conditions without affecting LDL cholesterol or HDL cholesterol. A triglyceride-raising effect without heterogeneity was seen only in type 2 diabetes when the reference carbohydrate was starch (mean difference 0.24 [95% CI 0.05-0.44]), dose was >60 g/day (0.18 [0.00-0.37]), or follow-up was < or =4 weeks (0.18 [0.00-0.35]). Piecewise meta-regression confirmed a dose threshold of 60 g/day (R(2) = 0.13)/10% energy (R(2) = 0.36). A total cholesterol-lowering effect without heterogeneity was seen only in type 2 diabetes under the following conditions: no randomization and poor study quality (-0.19 [-0.34 to -0.05]), dietary fat >30% energy (-0.33 [-0.52 to -0.15]), or crystalline fructose (-0.28 [-0.47 to -0.09]). Multivariate meta-regression analyses were largely in agreement.Conclusions: Pooled analyses demonstrated conditional triglyceride-raising and total cholesterol-lowering effects of isocaloric fructose exchange for carbohydrate in type 2 diabetes. Recommendations and large-scale future trials need to address the heterogeneity in the data. [ABSTRACT FROM AUTHOR]

Emerging evidence demonstrates an opportunity for using probiotics to support bone health but findings in humans are limited. This systematic review investigated if probiotic supplementation improves bone mineral density and bone structure in rodent models compared to no supplementation. Studies (n = 71) examining the effect of oral consumption of any probiotic strain on bone mineral density or bone structure in rodents were included. Meta-analyses were conducted separately by study model (intact, ovariectomized) and bone site (femur, tibia, spine) to determine the probiotic effect (standardized mean difference, SMD) on volumetric bone mineral density (vBMD), bone volume fraction (BV/TV) and cortical thickness (Ct.Th). Reasons for heterogeneity were explored (probiotic genus, sex, type of rodent). In intact rodents, probiotics resulted in greater vBMD (SMD = 0.43, 95% CI [0.13, 0.74], I2 = 3%, P<.05) and higher BV/TV (SMD = 0.63, 95% CI [0.25, 1.02], I2 = 57%, P<.05) at the femur without changes in cortical bone structure. In ovariectomized models, probiotic supplementation resulted in greater vBMD (femur: SMD = 1.28, 95% CI [1.01, 1.55], I2 = 3%, P<.05; tibia: SMD = 1.29, 95% CI [0.52, 2.05], I2 = 67%, P<.05; and spine: SMD = 1.47, 95% CI [0.97, 1.97], I2 = 26%, P<.05) as well as higher BV/TV (femur: SMD = 1.16, 95% CI [0.80, 1.52], I2 = 56%, P<.05; tibia: SMD = 2.13; 95% CI [1.09, 3.17], I2 = 79%, P<.05; spine: SMD = 2.04, 95% CI [1.17, 2.90], I2 = 76%, P<.05) and Ct.Th at the tibia (SMD = 2.35; 95% CI [0.72, 3.97], I2 = 82%, P<.05) but not at the femur versus control. The syntheses support probiotics as a strategy to improve bone outcomes in rodent models., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Background: Many clinical practice guidelines recommend dietary pulses for the prevention and management of cardiovascular disease and diabetes. The impact of extracted pulse proteins remains unclear. We therefore conducted a systematic review and meta-analysis of randomized controlled trials of the effect of extracted pulse proteins on therapeutic lipid targets., Methods and Findings: MEDLINE, Embase, and the Cochrane Library were searched through April 2024 for trials of ≥3-weeks. The primary outcome was low-density lipoprotein-cholesterol (LDL-C). The secondary outcomes were other lipid targets. Independent reviewers extracted data and assessed the risk of bias. Subgroup analyses included by pulse type and the certainty of evidence was assessed using GRADE., Results: Seven included trials (14 trial comparisons, n = 453) with a median of 4-weeks duration and dose of 35 g/day showed that extracted pulse proteins decreased LDL-C by -0.23 mmol/L (95% confidence interval: -0.36 to -0.10 mmol/L, p < 0.001). Similar effects were observed for non-high-density lipoprotein-cholesterol and apolipoprotein B. No interactions were found by pulse type. Subgroup analyses revealed effect modification by sex, with greater proportions of females seeing greater reductions. GRADE was generally moderate., Conclusions: Extracted pulse proteins likely result in moderate reductions in LDL-C and other lipid targets. Future studies on various types of extracted pulse proteins including assessments by sex are warranted.

Objectives: Long-term exposure to air pollution has been associated with higher risk of cardiovascular mortality. Less is known about the association of air pollution with initial development of cardiovascular disease. Herein, the association between low-level exposure to air pollutants and subclinical carotid atherosclerosis in adults without known clinical cardiovascular disease was investigated., Design: Cross-sectional analysis within a prospective cohort study., Setting: The Canadian Alliance for Healthy Hearts and Minds Cohort Study; a pan-Canadian cohort of cohorts., Participants: Canadian adults (n = 6645) recruited between 2014-2018 from the provinces of British Columbia, Alberta, Ontario, Quebec, and Nova Scotia, were studied, for whom averages of exposures to nitrogen dioxide (NO2), ozone (O3), and fine particulate matter (PM2.5) were estimated for the years 2008-2012., Main Outcome Measure: Carotid vessel wall volume (CWV) measured by magnetic resonance imaging (MRI)., Results: In adjusted linear mixed models, PM2.5 was not consistently associated with CWV (per 5 μg/m3 PM2.5; adjusted estimate = -8.4 mm3; 95% Confidence Intervals (CI) -23.3 to 6.48; p = 0.27). A 5 ppb higher NO2 concentration was associated with 11.8 mm3 lower CWV (95% CI -16.2 to -7.31; p<0.0001). A 3 ppb increase in O3 was associated with 9.34 mm3 higher CWV (95% CI 4.75 to 13.92; p<0.0001). However, the coarse/insufficient O3 resolution (10 km) is a limitation., Conclusions: In a cohort of healthy Canadian adults there was no consistent association between PM2.5 or NO2 and increased CWV as a measure of subclinical atherosclerosis by MRI. The reasons for these inconsistent associations warrant further study., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: RJ de Souza has served as an external resource person to the World Health Organization’s Nutrition Guidelines Advisory Group on trans fats, saturated fats, and polyunsaturated fats. The WHO paid for his travel and accommodation to attend meetings from 2012-2017 to present and discuss this work. He has presented updates of this work to the WHO in 2022. He has also done contract research for the Canadian Institutes of Health Research’s Institute of Nutrition, Metabolism, and Diabetes, Health Canada, and the World Health Organization for which he received remuneration. He has received speaker’s fees from the University of Toronto, and McMaster Children’s Hospital. He has held grants from the Canadian Institutes of Health Research, Canadian Foundation for Dietetic Research, Population Health Research Institute, and Hamilton Health Sciences Corporation as a principal investigator, and is a co-investigator on several funded team grants from the Canadian Institutes of Health Research. He has served as an independent director of the Helderleigh Foundation (Canada). He serves as a member of the Nutrition Science Advisory Committee to Health Canada (Government of Canada), and a co-opted member of the Scientific Advisory Committee on Nutrition (SACN) Subgroup on the Framework for the Evaluation of Evidence (Public Health England). Dr Anand reported receiving grants from Canadian Partnership Against Cancer, Heart and Stroke Foundation of Canada, and Canadian Institutes of Health Research, and a Canadian Institutes of Health Research Foundation grant during the conduct of the study and serving as the Tier 1 Canada Research Chair Ethnicity and Cardiovascular Disease and as the Michael G Degroote Heart and Stroke Foundation Chair in Population Health Research, and receiving grants from Heart and Stroke Foundation of Canada and Canadian Institutes of Health Research, and receiving personal fees from Bayer outside the submitted work. Dr Friedrich reported receiving personal fees from Circle CVI Inc for serving as a board member and adviser and being a shareholder outside the submitted work. Dr Dummer reported receiving grants from Canadian Partnership Against Cancer during the conduct of the study. Dr Lear reported receiving grants from the Canadian Institutes of Health Research and grants from Michael Smith Foundation for Health Research during the conduct of the study and personal fees from Curatio Inc outside the submitted work. Dr Tardif reported receiving grants from Amarin, Ceapro, Esperion, Ionis, Novartis, Pfizer, RegenXBio, Sanofi, AstraZeneca, and DalCor Pharmaceuticals, receiving personal fees from AstraZeneca, HLS Pharmaceuticals, Pendopharm, and DalCor Pharmaceuticals, and having a minor equity interest in DalCor Pharmaceuticals Minor outside the submitted work. In addition, Dr Tardif had a patent for Pharmacogenomics-Guided CETP Inhibition issued by DalCor Pharmaceuticals, a patent for Use of Colchicine After Myocardial Infarction pending, and a patent for Genetic Determinants of Response to Colchicine pending. No other disclosures were reported. Dr Brauer served on the WHO Guideline Development Group (no remuneration was provided but travel costs to meetings were covered). This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Azab et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Maternal diet may modulate human milk microbiota, but the effects of nutritional supplements are unknown. We examined the associations of prenatal diet and supplement use with milk microbiota composition. Mothers reported prenatal diet intake and supplement use using self-administered food frequency and standardised questionnaires, respectively. The milk microbiota was profiled using 16S rRNA gene sequencing. Associations of prenatal diet quality, dietary patterns, and supplement use with milk microbiota diversity and taxonomic structure were examined using Wilcoxon signed-rank tests and multivariable models adjusting for relevant confounders. A subset of 645 mothers participating in the CHILD Cohort Study (originally known as the Canadian Healthy Infant Longitudinal Development Study) provided one milk sample between 2 and 6 months postpartum and used prenatal multivitamin supplements ≥4 times a week. After adjusting for confounders, vitamin C supplement use was positively associated with milk bacterial Shannon diversity ( β = 0.18, 95% CI = 0.05, 0.31) and Veillonella and Granulicatella relative abundance ( β = 0.54; 95% CI = 0.05, 1.03 and β = 0.44; 95% CI = 0.04, 0.84, respectively), and negatively associated with Finegoldia relative abundance ( β = -0.31; 95% CI = -0.63, -0.01). Fish oil supplement use was positively associated with Streptococcus relative abundance ( β = 0.26; 95% CI = 0.03, 0.50). Prenatal diet quality and dietary patterns were not associated with milk microbiota composition. Prenatal vitamin C and fish oil supplement use were associated with differences in the milk microbiota composition. Future studies are needed to confirm our findings and elucidate mechanisms linking maternal supplement use to milk microbiota and child health., Competing Interests: The authors report no conflicts of interest., (© The Author(s) 2024.)

Background: Maternal smoking has been linked to adverse health outcomes in newborns but the extent to which it impacts newborn health has not been quantified through an aggregated cord blood DNA methylation (DNAm) score. Here, we examine the feasibility of using cord blood DNAm scores leveraging large external studies as discovery samples to capture the epigenetic signature of maternal smoking and its influence on newborns in White European and South Asian populations., Methods: We first examined the association between individual CpGs and cigarette smoking during pregnancy, and smoking exposure in two White European birth cohorts (n=744). Leveraging established CpGs for maternal smoking, we constructed a cord blood epigenetic score of maternal smoking that was validated in one of the European-origin cohorts (n=347). This score was then tested for association with smoking status, secondary smoking exposure during pregnancy, and health outcomes in offspring measured after birth in an independent White European (n=397) and a South Asian birth cohort (n=504)., Results: Several previously reported genes for maternal smoking were supported, with the strongest and most consistent association signal from the GFI1 gene (6 CpGs with p<5 × 10 -5 ). The epigenetic maternal smoking score was strongly associated with smoking status during pregnancy (OR = 1.09 [1.07, 1.10], p=5.5 × 10 -33 ) and more hours of self-reported smoking exposure per week (1.93 [1.27, 2.58], p=7.8 × 10 -9 ) in White Europeans. However, it was not associated with self-reported exposure (p>0.05) among South Asians, likely due to a lack of smoking in this group. The same score was consistently associated with a smaller birth size (-0.37±0.12 cm, p=0.0023) in the South Asian cohort and a lower birth weight (-0.043±0.013 kg, p=0.0011) in the combined cohorts., Conclusions: This cord blood epigenetic score can help identify babies exposed to maternal smoking and assess its long-term impact on growth. Notably, these results indicate a consistent association between the DNAm signature of maternal smoking and a small body size and low birth weight in newborns, in both White European mothers who exhibited some amount of smoking and in South Asian mothers who themselves were not active smokers., Funding: This study was funded by the Canadian Institutes of Health Research Metabolomics Team Grant: MWG-146332., Competing Interests: WD, NC, NC, SA, Rd, AL, KM, SA, PS, ST, TM, KT, PM, MA, ES, GP, SA No competing interests declared, (© 2024, Deng et al.)

We evaluated the effectiveness of COVID-19 vaccines among South Asians living in Ontario, Canada compared to non-South Asians and compared the odds of symptomatic COVID-19 infection and related hospitalizations and deaths among non-vaccinated South Asians and non-South Asians. This was a test negative design study conducted in Ontario, Canada between December 14, 2020 and November 15, 2021. All eligible individuals >18 years with symptoms of COVID-19 were subdivided by ethnicity (South Asian vs other) and vaccination status (vaccinated versus not). The primary outcome was vaccine effectiveness as defined by COVID-19 infections, hospitalizations, and deaths, and secondary outcome was the odds of COVID-19 infections, hospitalizations, and death comparing non-vaccinated South Asians to non-vaccinated non-South Asians. 883,155 individuals were included. Among South Asians, two doses of COVID-19 vaccine prevented 93.8% (95% CI 93.2, 94.4) of COVID-19 infections and 97.5% (95% CI 95.2, 98.6) of hospitalizations and deaths. Among non-South Asians, vaccines prevented 86.6% (CI 86.3, 86.9) of COVID-19 infections and 93.1% (CI 92.2, 93.8) of hospitalizations and deaths. Non-vaccinated South Asians had higher odds of symptomatic SARS-CoV-2 infection compared to non-vaccinated non-South Asians (OR 2.35, 95% CI 2.3, 2.4), regardless of their immigration status. COVID-19 vaccines are effective in preventing infections, hospitalizations and deaths among South Asians living in Canada. The observation that non-vaccinated South Asians have higher odds of symptomatic COVID-19 infection warrants further investigation., Competing Interests: The authors have read the journal’s policy and have the following competing interests: SSA holds a Tier 1 Canada Research Chair in Ethnic Diversity and Cardiovascular Disease (#CRC-2017-00024), and the Michael G DeGroote Heart and Stroke Foundation of Canada Chair in Population Health Research outside of the submitted work. ML sits on vaccine advisory boards for Seqirus, Pfizer, Sanofi, Medicago, GSK, Merck, Novovax, and Janssen; is on the Data Safety Monitoring Board for CanSino Biologics, has received funding from Seqirus for a vaccine trial, is receiving in-kind supply of smallpox vaccines from Bavarian Nordic, and has provided expert testimony about vaccines outside of the submitted work. DMEB holds a Tier 2 Canada Research Chair in Aging and Immunity, sits on vaccine advisory boards for Pfizer and AstraZeneca, has received consulting fees/honoraria for Pfizer and AstraZeneca, and has provided expert testimony about vaccines outside of the submitted work. SB is the Director of the Centre for Vaccine Preventable Diseases (CVPD) at the University of Toronto outside of the submitted work. The CVPD receives operational support from a mix of funding sources, including through donations from pharmaceutical companies. A robust set of governance practices are in place to safeguard the academic freedom of the CVPD. BRS is funded by the University of Toronto as the Novo Nordisk Research Chair in Equitable Care of Diabetes and Related Conditions outside of the submitted work. DS holds the Heather M. Arthur Population Health Research Institute/Hamilton Health Sciences Chair in Inter-Professional Health Research and has received an honorarium from Diabetes Update 2023 for being an invited speaker and is a co-methods lead on the Diabetes Canada Clinical Practice Guidelines Steering Committee outside of the submitted work. GW has received grants from the Canadian Institutes of Health Research and the Hamilton Health Sciences Foundation outside of the submitted work. RJdS has received grants from the Canadian Institutes of Health Research, Canadian Foundation for Dietetic Research, Population Health Research Institute, and Hamilton Health Sciences Corporation; he has received consulting fees and travel honoraria from the World Health Organization’s Nutrition Guidelines Advisory Group; he is an Independent Director for the Helderleigh Foundation (Canada) and Co-Chair of a method working group for the ADA/EASD Precision Medicine in Diabetes group outside of the submitted work. SIB has received grants from the Canadian Institutes of Health Research and from the International Development Research Centre; he also served as a member of the US National Institute of Allergy and Infectious Diseases Data and Safety Monitoring Board for COVID-19 Preventive monoclonal antibodies trials outside of the submitted work. All other authors declare that they have no competing interests. This does not alter our adherence to PLOS policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare., (Copyright: © 2024 Chanchlani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Red and processed meat is considered risk factors of gestational diabetes mellitus (GDM), but the evidence is inconclusive. We aimed to examine the association between red and processed meat intake and odds of GDM among South Asian and White European women living in Canada., Methods: This is a cross-sectional analysis of pregnant women from two birth cohorts: SouTh Asian biRth cohorT (START; n = 976) and Family Atherosclerosis Monitoring In earLY life (FAMILY; n = 581). Dietary intake was assessed using a validated 169-item semi-quantitative food-frequency questionnaire (FFQ). Multivariate logistic regression models were used to examine the associations between gestational diabetes and: 1) total red and processed meat; 2) unprocessed red meat; 3) processed meat and GDM after adjustment for potential confounders., Results: There were 241 GDM cases in START and 91 in FAMILY. The median total red and processed meat intake were 1.5 g/d (START) and 52.8 g/d (FAMILY). In START, the multivariable-adjusted odds ratio (OR) showed neither lower nor higher intakes of unprocessed red meat (p-trend = 0.68), processed meat (p-trend = 0.90), or total red and processed meat (p-trend = 0.44), were associated with increased odds of GDM, when compared with medium intake. Similar results were observed in FAMILY except for processed meat intake [OR = 0.94 (95% CI 0.47-1.91), for medium versus low and OR = 1.51 (95% CI 0.77-2.29) for medium versus high; p-trend = 0.18] after adjusting for additional dietary factors such as the diet quality score, total fiber, saturated fat and glycemic load., Conclusion: Medium compared with low or high red and processed meat intake is not associated with GDM in White Europeans and South Asians living in Canada., Competing Interests: Hertzel C. Gerstein holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care. He reports research grants from Eli Lilly, AstraZeneca, Novo Nordisk, and Sanofi; honoraria for speaking from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, DKSH, Zuellig, Roche, Sanofi, Jiangsu Hanson, and Carbon Brand; and consulting fees from Abbott, Eli Lilly, Novo Nordisk, Sanofi, Kowa, Pfizer, Hanmi and Viatris. Russell J. de Souza has served as an external resource person to the World Health Organization’s Nutrition Guidelines Advisory Group on trans fats, saturated fats, and polyunsaturated fats. The WHO paid for his travel and accommodation to attend meetings from 2012-2017 to present and discuss this work. He has also done contract research for the Canadian Institutes of Health Research’s Institute of Nutrition, Metabolism, and Diabetes, Health Canada, and the World Health Organization for which he received remuneration. He has received speaker’s fees from the University of Toronto, and McMaster Children’s Hospital. He has held grants from the Canadian Institutes of Health Research, Canadian Foundation for Dietetic Research, Population Health Research Institute, and Hamilton Health Sciences Corporation as a principal investigator, and is a co-investigator on several funded team grants from the Canadian Institutes of Health Research. He serves as a member of the Nutrition Science Advisory Committee to Health Canada (Government of Canada), a co-opted member of the Scientific Advisory Committee on Nutrition (SACN) Subgroup on the Framework for the Evaluation of Evidence (Public Health England), and as an independent director of the Helderleigh Foundation (Canada). These affiliations do not alter our adherence to PLOS ONE policies on sharing data and materials. START has not received funding/assistance from a commercial organization., (Copyright: © 2024 Stennett et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: South Asians represent the largest non-white ethnic group in Canada and were disproportionately impacted by the COVID-19 pandemic. We sought to determine the factors associated with vaccine hesitancy in South Asian Canadians., Methods: We conducted a cross-sectional analysis of vaccine hesitancy using data collected at the baseline assessment of a prospective cohort study, COVID CommUNITY South Asian. Participants (18 + years) were recruited from the Greater Toronto and Hamilton Area in Ontario (ON) and the Greater Vancouver Area in British Columbia (BC) between April and November 2021. Demographic characteristics and vaccine attitudes measured by the Vaccine Attitudes Examination (VAX) scale were collected. Each item is scored on a 6-point Likert scale, and higher scores reflect greater hesitancy. A multivariable linear mixed effects model was used to identify sociodemographic factors associated with vaccine hesitancy, adjusting for multiple covariates., Results: A total of 1496 self-identified South Asians (52% female) were analyzed (mean age = 38.5 years; standard deviation (SD): 15.3). The mean VAX score was 3.2, SD: 0.8 [range: 1.0‒6.0]. Factors associated with vaccine hesitancy included: time since immigration (p = 0.04), previous COVID-19 infection (p < 0.001), marital status (p < 0.001), living in a multigenerational household (p = 0.03), age (p = 0.02), education (p < 0.001), and employment status (p = 0.001)., Conclusion: Among South Asians living in ON and BC, time since immigration, prior COVID-19 infection, marital status, living in a multigenerational household, age, education, and employment status were associated with vaccine hesitancy. This information can be used to address vaccine hesitancy in the South Asian population in future COVID-19 waves or pandemics., (© 2024. The Author(s).)

Health care contributes 4·4% of global net carbon emissions. Hospitals are resource-intensive settings, using a large amount of supplies in patient care and have high energy, ventilation, and heating needs. This Viewpoint investigates emissions related to health care in a patient's last year of life. End of life (EOL) is a period when health-care use and associated emissions production increases exponentially due primarily to hospital admissions, which are often at odds with patients' values and preferences. Potential solutions detailed within this Viewpoint are facilitating advanced care plans with patients to ensure their EOL wishes are clear, beginning palliative care interventions earlier when treating a life-limiting illness, deprescribing unnecessary medications because medications and their supply chains make up a significant portion of health-care emissions, and, enhancing access to low-intensity community care settings (eg, hospices) within the last year of life if home care is not available. Our analysis was done using Canadian data, but the findings can be applied to other high-income countries., Competing Interests: Declaration of interests MS is a physician, advocate, and leader of provincial and national health-care sustainability organisations. MS has been paid for seven presentations on topics similar to those of this Viewpoint within the last 36 months. These presentations have been with the Royal Botanical Gardens, University of British Columbia, the American Academy of Family Physicians, Annual Thomas Fear and Alice Morgans Fear Memorial Conference, McMaster University's Department of Engineering, McMaster University Care of the Elderly Department, and York University CANSEE Conference. MS holds leadership roles with the Canadian Coalition of Green Health Care (Executive Director) and Partnerships for Environmental Action with Clinicians and Communities for Hospitals/Health Care Facilities (co-lead). OL is a physician with a background in health-care sustainability quality improvement. SK is the co-director of The Starfish, an environmental sustainability charity. SK is also co-lead of Partnerships for Environmental Action with Clinicians and Communities for Hospitals/Health Care Facilities. RJdS is a dietitian and Associate Professor interested in global health and sustainability from the perspective of nutrition. RJdS has served as an external resource person to WHO's Guidelines Advisory Group on trans fats, saturated fats, and polyunsaturated fats. WHO paid for his travel and accommodation to attend meetings from 2012 to 2017 to discuss and present this work. RJdS has presented updates of this work to WHO in 2022; has done contract research for the Canadian Institutes of Health Research's Institute of Nutrition, Metabolism, and Diabetes, Health Canada, and WHO for which he received remuneration; has received speaker's fees from the University of Toronto and McMaster Children's Hospital; has served as an independent director of the Helderleigh Foundation (Canada); serves as a member of the Nutrition Science Advisory Committee to Health Canada (Government of Canada), co-chair of the Method working group of the ADA/EASD Precision Medicine in Diabetes group, and is a co-opted member of the Scientific Advisory Committee on Nutrition Subgroup on the Framework for the Evaluation of Evidence (Public Health England); has held grants from the Canadian Institutes of Health Research, Canadian Foundation for Dietetic Research, Population Health Research Institute, and Hamilton Health Sciences Corporation as a principal investigator; and is a co-investigator on several funded team grants from the Canadian Institutes of Health Research. SSA is a professor of medicine and epidemiology and associate vice-president for global health at McMaster University; holds a Canada Research Chair in Ethnic Diversity and Cardiovascular Disease and the Michael G DeGroote Heart and Stroke Foundation of Canada endowed Chair in Population Health; and has received speaking and consultancy fees from pharmaceutical companies Bayer, Novartis, Servier, and Novo Nordisk., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC license. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (© 2024. The Author(s).)

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 I 2 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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., (©Sikander Z Texiwala, Russell J de Souza, Suzette Turner, Sheldon M Singh. Originally published in JMIR Cardio (https://cardio.jmir.org), 05.02.2024.)

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., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to underscore the issues associated with the dichotomization of categories in sleep questionnaires among women diagnosed with endometriosis and sleep disturbances, as well as their potential impact on the validity of the research findings., Background: A range of questionnaires is employed across settings from primary care to research to classify sleep disturbances. Insomnia Severity Index (ISI) and the Pittsburgh Sleep Quality Index (PSQI) are two frequently utilized instruments for evaluating sleep. Nonetheless, these tools may produce divergent outcomes when applied to the same population., Methods: To evaluate the sleep quality of patients with deep endometriosis (DE), two self-administered questionnaires were utilized: ISI and PSQI. Patients rated their average pelvic pain over the preceding four weeks on a numeric rating scale (NRS) ranging from 0 to 10. Patients with an ISI score >14 or PSQI >5 were classified as poor sleepers, while the others as good sleepers., Results: Among the 161 patients who completed both sleep questionnaires, 129 (80 %) rated their subjective sleep quality as good. However, when the scores from the sleep questionnaires were analyzed, only 17 (11 %) patients were classified as good sleepers by the PSQI, whereas the ISI classified 83 (52 %) patients as good sleepers. When comparing the standardized scores, moderate to good reliability was found (intraclass correlation coefficient, 0.76; 95 % confidence interval, 0.69-0.82)., Conclusion: Both questionnaires yield consistent scores that seem comparable in women with DE; however, the cutoff values seem inadequate for this population. Therefore, we can probably rely on both questionnaire scores, yet their recommended cutoff values should be approached with caution., Competing Interests: Declaration of competing interest We inform you that there are no conflicts of interest concerning the production of our document entitled “Challenges in measuring sleep quality among women with endometriosis: a comparison of two questionnaires.”, (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., (© 2024. The Author(s).)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Talukdar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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 ( I 2  = 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., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Z. Chagla has advised and/or received speaker from Merck, Pfizer, Moderna, AstraZeneca, Gilead, GSK, Roche, and Avir. He has received research grants from 10.13039/100004334Merck, 10.13039/100005564Gilead, and 10.13039/100004337Roche.R. J. de Souza has served as an external resource person to the World Health Organization's Nutrition Guidelines Advisory Group on trans fats, saturated fats, and polyunsaturated fats. The WHO paid for his travel and accommodation to attend meetings from 2012 to 2017 to present and discuss this work. He has presented updates of this work to the WHO in 2022. He has also done contract research for the Canadian Institutes of Health Research's Institute of Nutrition, Metabolism, and Diabetes, Health Canada, and the World Health Organization for which he received remuneration. He has received speaker's fees from the 10.13039/501100003579University of Toronto, and McMaster Children's Hospital. He has served as an independent director of the Helderleigh Foundation (Canada). He serves as a member of the Nutrition Science Advisory Committee to Health Canada (Government of Canada), co-chair of the Method working group of the ADA/EASD Precision Medicine in Diabetes group, and is a co-opted member of the Scientific Advisory Committee on Nutrition (SACN) Subgroup on the Framework for the Evaluation of Evidence (Public Health England). He has held grants from the 10.13039/501100000024Canadian Institutes of Health Research, 10.13039/501100000203Canadian Foundation for Dietetic Research, Population Health Research Institute, and 10.13039/100008360Hamilton Health Sciences Corporation as a principal investigator, and is a co-investigator on several funded team grants from the 10.13039/501100000024Canadian Institutes of Health Research.M. Munir, F. Rabbi, A. Mayhew, and L. Banfield report no competing interests., (© 2023 The Authors.)

Introduction and Hypothesis: Painful bladder syndrome (PBS) is frequently associated with deep endometriosis (DE), and both conditions cause chronic pelvic pain (CPP), which often impairs sleep quality. This study was aimed at analyzing the impact of CPP plus PBS in women with DE on the global sleep quality index using the Pittsburgh Sleep Quality Index (PSQI) and subsequently examine each sleep dimension., Methods: One hundred and forty women with DE were included and answered the PSQI and the O'Leary-Sant Interstitial Cystitis Symptoms and Problem Index questionnaires with or without CPP. Women were categorized into good or poor sleepers using the PSQI cutoff; subsequently, a linear regression model was used to analyze the PSQI score and a logistic regression model for each questionnaire's sleep component., Results: Only 13% of women with DE had a good sleep. Approximately 20% of those with DE but no/mild pain were good sleepers; 138 women with DE (88.5%), 94% with PBS, and 90.5% with moderate/severe pain were poor sleepers. For PSQI components, CPP worsened the subjective sleep quality by more than threefold (p = 0.019), increased sleep disturbances by nearly sixfold (p = 0.03), and decreased the sleep duration by practically sevenfold (p = 0.019). Furthermore, PBS increased sleep disturbances by nearly fivefold (p < 0.01)., Conclusions: The addition of PBS to CPP in women with DE is devastating for overall sleep quality, probably because it impacts some sleep dimensions unaffected by CPP and amplifies the problem in those already affected by pain., (© 2023. The International Urogynecological Association.)

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., Competing Interests: The authors have read the journal’s policy and have the following competing interests: Dr. Sonia S. Anand has received paid consultancy fees and speaking honoraria from Novartis. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Wahi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (© 2023. BioMed Central Ltd., part of Springer Nature.)

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., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: LC is a Mitacs-Elevate post-doctoral fellow jointly funded by the Government of Canada and the Canadian Sugar Institute. She was previously employed as a casual clinical coordinator at INQUIS Clinical Research, Ltd. (formerly Glycemic Index Laboratories, Inc.), a contract research organization. SA-C has received funding from CIHR Canadian Graduate Scholarship-Master’s, the Loblaw Food as Medicine Award, and the Ontario Graduate Scholarship. AA and AC have received funding from a Toronto 3D MSc Scholarship award. TAK has received research support from the Canadian Institutes of Health Research (CIHR), the International Life Science Institute (ILSI), and National Honey Board. He has been an invited speaker at the Calorie Control Council Annual meeting for which he has received an honorarium. He was funded by a Toronto 3D Postdoctoral Fellowship Award. FA-Y is a part-time Research Assistant at INQUIS Clinical Research, Ltd., a contract research organization. DL reports receiving a stipend from University of Toronto Department of Nutritional Sciences Graduate Student Fellowship, University of Toronto Fellowship in Nutritional Sciences, University of Toronto Supervisor’s Research Grant - Early Researcher Awards, and Dairy Farmers of Canada Graduate Student Fellowships; a scholarship from St. Michael’s Hospital Research Training Centre, and a University of Toronto School of Graduate Studies Conference Grant. AZ is a part-time Research Associate at INQUIS Clinical Research, Ltd., a contract research organization, and has received funding from a BBDC Postdoctoral Fellowship. RJdS has served as an external resource person to the World Health Organization’s Nutrition Guidelines Advisory Group on trans fats, saturated fats, and polyunsaturated fats. The WHO paid for his travel and accommodation to attend meetings from 2012-2017 to present and discuss this work. He has also done contract research for the Canadian Institutes of Health Research’s Institute of Nutrition, Metabolism, and Diabetes, Health Canada, and the World Health Organization for which he received remuneration. He has received speaker’s fees from the University of Toronto, and McMaster Children’s Hospital. He has held grants from the Canadian Foundation for Dietetic Research, Population Health Research Institute, and Hamilton Health Sciences Corporation as a principal investigator, and is a co-investigator on several funded team grants from Canadian Institutes of Health Research. He has served as an independent director of the Helderleigh Foundation (Canada). He serves as a member of the Nutrition Science Advisory Committee to Health Canada (Government of Canada), and is a co-opted member of the Scientific Advisory Committee on Nutrition (SACN) Subgroup on the Framework for the Evaluation of Evidence (Public Health England). TMSW is an employee of INQUIS Clinical Research, Toronto, Canada, and has authored several diet books on the glycaemic index for which he has received royalties from Phillipa Sandall Publishing Services and CABI Publishers; and has received consultant fees, honorariums, travel funding, or research support from or served on the scientific advisory board for Canadian Institutes of Health Research, Canadian Diabetes Association, Dairy Farmers of Canada, McCain Foods, Temasek Polytechnic, Northwestern University, Royal Society of London, Glycemic Index Symbol programme, CreaNutrition AG, McMaster University, Canadian Society for Nutritional Sciences, National Sports and Conditioning Association, Faculty of Public Health and Nutrition—Autonomous University of Nuevo Leon, and Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes. CWCK has received grants or research support from the Advanced Food Materials Network, Agriculture and Agri-Foods Canada, Almond Board of California, American Pistachio Growers, Barilla, Calorie Control Council, Canadian Institutes of Health Research, Canola Council of Canada, International Nut and Dried Fruit Council, International Tree Nut Council Research and Education Foundation, Loblaw Brands, Pulse Canada, Saskatchewan Pulse Growers and Unilever; has received in-kind research support from the Almond Board of California, American Peanut Council, Barilla, California Walnut Commission, Kellogg Canada, Loblaw Companies, Quaker (PepsiCo), Primo, Unico, Unilever, WhiteWave Foods; has received travel support or honorariums from the American Peanut Council, American Pistachio Growers, Barilla, California Walnut Commission, Canola Council of Canada, General Mills, International Nut and Dried Fruit Council, International Pasta Organization, Loblaw Brands Ltd, Nutrition Foundation of Italy, Oldways Preservation Trust, Paramount Farms, Peanut Institute, Pulse Canada, Sabra Dipping, Saskatchewan Pulse Growers, Sun-Maid, Tate & Lyle, Unilever and White Wave Foods; has served on the scientific advisory board for the International Tree Nut Council, International Pasta Organization, Lantmannen, McCormick Science Institute, Oldways Preservation Trust, Paramount Farms and Pulse Canada; is a member of the International Carbohydrate Quality Consortium, executive board member of the Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes; is on the Clinical Practice Guidelines Expert Committee for Nutrition Therapy of the European Association for the Study of Diabetes; and is a director of the Toronto 3D Knowledge Synthesis and Clinical Trials Foundation. DJAJ has received research grants from Saskatchewan & Alberta Pulse Growers Associations, the Agricultural Bioproducts Innovation Program through the Pulse Research Network, the Advanced Foods and Material Network, Loblaw Companies Ltd., Unilever Canada and Netherlands, Barilla, the Almond Board of California, Agriculture and Agri-food Canada, Pulse Canada, Kellogg’s Company, Canada, Quaker Oats, Canada, Procter & Gamble Technical Centre Ltd., Bayer Consumer Care, Springfield, NJ, Pepsi/Quaker, International Nut & Dried Fruit Council (INC), Soy Foods Association of North America, the Coca-Cola Company (investigator initiated, unrestricted grant), Solae, Haine Celestial, the Sanitarium Company, Orafti, the International Tree Nut Council Nutrition Research and Education Foundation, the Peanut Institute, Soy Nutrition Institute (SNI), the Canola and Flax Councils of Canada, the Calorie Control Council, the Canadian Institutes of Health Research (CIHR), the Canada Foundation for Innovation (CFI)and the Ontario Research Fund (ORF). He has received in-kind supplies for trials as a research support from the Almond board of California, Walnut Council of California, American Peanut Council, Barilla, Unilever, Unico, Primo, Loblaw Companies, Quaker (Pepsico), Pristine Gourmet, Bunge Limited, Kellogg Canada, WhiteWave Foods. He has been on the speaker’s panel, served on the scientific advisory board and/or received travel support and/or honoraria from 2020 China Glycemic Index (GI) International Conference, Atlantic Pain Conference, Academy of Life Long Learning, the Almond Board of California, Canadian Agriculture Policy Institute, Loblaw Companies Ltd, the Griffin Hospital (for the development of the NuVal scoring system), the Coca-Cola Company, Epicure, Danone, Diet Quality Photo Navigation (DQPN), Better Therapeutics (FareWell), Verywell, True Health Initiative (THI), Heali AI Corp, Institute of Food Technologists (IFT), Soy Nutrition Institute (SNI), Herbalife Nutrition Institute (HNI), Saskatchewan & Alberta Pulse Growers Associations, Sanitarium Company, Orafti, the American Peanut Council, the International Tree Nut Council Nutrition Research and Education Foundation, the Peanut Institute, Herbalife International, Pacific Health Laboratories, Nutritional Fundamentals for Health (NFH), Barilla, Metagenics, Bayer Consumer Care, Unilever Canada and Netherlands, Solae, Kellogg, Quaker Oats, Procter & Gamble, Abbott Laboratories, Dean Foods, the California Strawberry Commission, Haine Celestial, PepsiCo, the Alpro Foundation, Pioneer Hi-Bred International, DuPont Nutrition and Health, Spherix Consulting and WhiteWave Foods, the Advanced Foods and Material Network, the Canola and Flax Councils of Canada, Agri-Culture and Agri-Food Canada, the Canadian Agri-Food Policy Institute, Pulse Canada, the Soy Foods Association of North America, the Nutrition Foundation of Italy (NFI), Nutra-Source Diagnostics, the McDougall Program, the Toronto Knowledge Translation Group (St. Michael’s Hospital), the Canadian College of Naturopathic Medicine, The Hospital for Sick Children, the Canadian Nutrition Society (CNS), the American Society of Nutrition (ASN), Arizona State University, Paolo Sorbini Foundation and the Institute of Nutrition, Metabolism and Diabetes. He received an honorarium from the United States Department of Agriculture to present the 2013 W.O. Atwater Memorial Lecture. He received the 2013 Award for Excellence in Research from the International Nut and Dried Fruit Council. He received funding and travel support from the Canadian Society of Endocrinology and Metabolism to produce mini cases for the Canadian Diabetes Association (CDA). He is a member of the International Carbohydrate Quality Consortium (ICQC). His wife, Alexandra L Jenkins, is a director and partner of INQUIS Clinical Research for the Food Industry, his 2 daughters, Wendy Jenkins and Amy Jenkins, have published a vegetarian book that promotes the use of the foods described here, The Portfolio Diet for Cardiovascular Risk Reduction (Academic Press/Elsevier 2020 ISBN:978-0-12-810510-8)and his sister, Caroline Brydson, received funding through a grant from the St. Michael’s Hospital Foundation to develop a cookbook for one of his studies. JLS has received research support from the Canadian Foundation for Innovation, Ontario Research Fund, Province of Ontario Ministry of Research and Innovation and Science, Canadian Institutes of health Research (CIHR), Diabetes Canada, PSI Foundation, Banting and Best Diabetes Centre (BBDC), American Society for Nutrition (ASN), INC International Nut and Dried Fruit Council Foundation, National Dried Fruit Trade Association, National Honey Board (the U.S. Department of Agriculture [USDA] honey “Checkoff” program), International Life Sciences Institute (ILSI), Pulse Canada, Quaker Oats Center of Excellence, The United Soybean Board (the USDA soy “Checkoff” program), The Tate and Lyle Nutritional Research Fund at the University of Toronto, The Glycemic Control and Cardiovascular Disease in Type 2 Diabetes Fund at the University of Toronto (a fund established by the Alberta Pulse Growers), and The Nutrition Trialists Fund at the University of Toronto (a fund established by an inaugural donation from the Calorie Control Council). He has received in-kind food donations to support a randomized controlled trial from the Almond Board of California, California Walnut Commission, Peanut Institute, Barilla, Unilever/Upfield, Unico/Primo, Loblaw Companies, Quaker, Kellogg Canada, WhiteWave Foods/Danone, and Nutrartis. He has received travel support, speaker fees and/or honoraria from Diabetes Canada, Dairy Farmers of Canada, FoodMinds LLC, International Sweeteners Association, Nestlé, Pulse Canada, Canadian Society for Endocrinology and Metabolism (CSEM), GI Foundation, Abbott, General Mills, Biofortis, ASN, Northern Ontario School of Medicine, INC Nutrition Research & Education Foundation, European Food Safety Authority (EFSA), Comité Européen des Fabricants de Sucre (CEFS), Nutrition Communications, International Food Information Council (IFIC), Calorie Control Council, and Physicians Committee for Responsible Medicine. He has or has had ad hoc consulting arrangements with Perkins Coie LLP, Tate & Lyle, Wirtschaftliche Vereinigung Zucker e.V., Danone, and Inquis Clinical Research. He is a member of the European Fruit Juice Association Scientific Expert Panel and former member of the Soy Nutrition Institute (SNI) Scientific Advisory Committee. He is on the Clinical Practice Guidelines Expert Committees of Diabetes Canada, European Association for the study of Diabetes (EASD), Canadian Cardiovascular Society (CCS), and Obesity Canada/Canadian Association of Bariatric Physicians and Surgeons. He serves or has served as an unpaid scientific advisor for the Food, Nutrition, and Safety Program (FNSP) and the Technical Committee on Carbohydrates of ILSI North America. He is a member of the International Carbohydrate Quality Consortium (ICQC), Executive Board Member of the Diabetes and Nutrition Study Group (DNSG) of the EASD, and Director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. His wife is an employee of AB InBev. QL, AC, SBM, VLC, and LAL declare no competing interests. There are no products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Context: Excess calories from free sugars are implicated in the epidemics of obesity and type 2 diabetes. Honey is a free sugar but is generally regarded as healthy., Objective: The effect of honey on cardiometabolic risk factors was assessed via a systematic review and meta-analysis of controlled trials using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach., Data Sources: MEDLINE, Embase, and the Cochrane Library databases were searched up to January 4, 2021, for controlled trials ≥1 week in duration that assessed the effect of oral honey intake on adiposity, glycemic control, lipids, blood pressure, uric acid, inflammatory markers, and markers of nonalcoholic fatty liver disease., Data Extraction: Independent reviewers extracted data and assessed risk of bias. Data were pooled using the inverse variance method and expressed as mean differences (MDs) with 95%CIs. Certainty of evidence was assessed using GRADE., Data Analysis: A total of 18 controlled trials (33 trial comparisons, N = 1105 participants) were included. Overall, honey reduced fasting glucose (MD = -0.20 mmol/L, 95%CI, -0.37 to -0.04 mmol/L; low certainty of evidence), total cholesterol (MD = -0.18 mmol/L, 95%CI, -0.33 to -0.04 mmol/L; low certainty), low-density lipoprotein cholesterol (MD = -0.16 mmol/L, 95%CI, -0.30 to -0.02 mmol/L; low certainty), fasting triglycerides (MD = -0.13 mmol/L, 95%CI, -0.20 to -0.07 mmol/L; low certainty), and alanine aminotransferase (MD = -9.75 U/L, 95%CI, -18.29 to -1.21 U/L; low certainty) and increased high-density lipoprotein cholesterol (MD = 0.07 mmol/L, 95%CI, 0.04-0.10 mmol/L; high certainty). There were significant subgroup differences by floral source and by honey processing, with robinia honey, clover honey, and raw honey showing beneficial effects on fasting glucose and total cholesterol., Conclusion: Honey, especially robinia, clover, and unprocessed raw honey, may improve glycemic control and lipid levels when consumed within a healthy dietary pattern. More studies focusing on the floral source and the processing of honey are required to increase certainty of the evidence., Systematic Review Registration: PROSPERO registration number CRD42015023580., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

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., Competing Interests: Conflict of interest: D.W. has received honoraria from Amgen Canada, HLS Therapeutics Inc., and Sanofi–Aventis Canada. M.D. has no disclosures. R.d.S. has received grants from the Canadian Foundation for Dietetic Research, the Canadian Institutes of Health Research, the Hamilton Health Sciences Corporation, and the Population Health Research Institute; receiving personal and/or travel fees from Health Canada, McMaster Children’s Hospital, the University of Toronto, and the World Health Organization; serving as a member of the Nutrition Science Advisory Committee to Health Canada and the Scientific Advisory Committee on Nutrition Subgroup on the Framework for the Evaluation of Evidence (Public Health England); serving as an external resource person to the World Health Organization Nutrition Guidelines Advisory Group on trans fats, saturated fats, and polyunsaturated fats; and serving as an independent director of the Helderleigh Foundation outside the submitted work. C.R. has no disclosures. J.E. reports grants and personal fees from Bayer, Boehringer Ingelheim, Bristol–Myers Squibb/Pfizer, and Daiichi Sankyo, during the conduct of the study, and grants and personal fees from Bayer, Boehringer Ingelheim, Bristol–Myers Squibb/Pfizer, Daiichi Sankyo, Janssen, Astra Zeneca, Eli Lilly, Glaxo Smith Kline, and Sanofi Aventis, outside the submitted work. J.B. has no disclosures. A.M. reports personal fees from Novartis, Bayer, Fresenius, and Cardiorentis. D.B. discloses the following relationships—Advisory Board: AngioWave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Janssen, Level Ex, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; Board of Directors: AngioWave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock options), DRS.LINQ (stock options), Society of Cardiovascular Patient Care, and TobeSoft; Chair: Inaugural Chair, American Heart Association Quality Oversight Committee; data monitoring committees: Acesion Pharma, Assistance Publique–Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute, and Rutgers University (for the NIH-funded MINT Trial); honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol–Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS—II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), and Wiley (steering committee); other: Clinical Cardiology (Deputy Editor), NCDR–ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); research funding: Abbott, Acesion Pharma, Afimmune, Aker BioMarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol–Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, 89Bio; royalties: Elsevier (Editor, Braunwald’s Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, Svelte; Trustee: American College of Cardiology; unfunded research: FlowCo, Takeda. S.Y. has received research grants, honoraria, and travel expenses for lectures from Bayer, Boehringer Ingelheim, Bristol–Myers Squibb, and AstraZeneca. S.A. has received speaking honoraria and consulting fees from Bayer and speaking fees from Janssen., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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 (BMI AUC ) and skinfold thickness (SSF AUC ) scores were calculated from birth to 3 years as the total area under the growth curve (AUC). BMI AUC and/or SSF AUC >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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. RJ de Souza has served as an external resource person to the World Health Organization’s Nutrition Guidelines Advisory Group on trans fats, saturated fats, and polyunsaturated fats. The WHO paid for his travel and accommodation to attend meetings from 2012-2017 to present and discuss this work. He has presented updates of this work to the WHO in 2022. He has also done contract research for the Canadian Institutes of Health Research’s Institute of Nutrition, Metabolism, and Diabetes, Health Canada, and the World Health Organization for which he received remuneration. He has received speaker’s fees from the University of Toronto, and McMaster Children’s Hospital. He has served as an independent director of the Helderleigh Foundation (Canada). He serves as a member of the Nutrition Science Advisory Committee to Health Canada (Government of Canada), co-chair of the Method working group of the ADA/EASD Precision Medicine in Diabetes group, and is a co-opted member of the Scientific Advisory Committee on Nutrition (SACN) Subgroup on the Framework for the Evaluation of Evidence (Public Health England). He has held grants from the 10.13039/501100000024Canadian Institutes of Health Research, 10.13039/501100000203Canadian Foundation for Dietetic Research, Population Health Research Institute, and Hamilton Health Sciences Corporation as a principal investigator, and is a co-investigator on several funded team grants from the 10.13039/501100000024Canadian Institutes of Health Research., (© 2023 Published by Elsevier Ltd.)

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., (© 2023. The Author(s).)

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., Competing Interests: Competing interests: HSB has received Grants/Research Support (paid to his institution) from the following: Amgen, Anji, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Kowa, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Public Health Agency of Canada (PHAC) and Sanofi. HCG holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care. He reports research grants from Eli Lilly, AstraZeneca, Novo Nordisk, and Sanofi; honoraria for speaking from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, DKSH, Zuellig, Roche, Sanofi, Jiangsu Hanson, and Carbon Brand; and consulting fees from Abbott, Eli Lilly, Novo Nordisk, Sanofi, Kowa, Pfizer, Hanmi and Viatris. SK received a CIHR video talks Prize for the Knowledge Translation (KT) video created for the South Asian Grandmothers Qualitative Substudy. She was also funded by a CIHR Vanier Doctoral scholarship to develop and evaluate the SMART START KT tools. PR is currently funded by the Canadian Institutes of Health (CIHR) (2021–2025). He coordinates research with NexJ Health, which provides a software platform to convey the psychosocial and psychiatric programming he develops and assesses. PR receives no personal compensations for studies coordinated with NexJ but does receive free-of-charge platform support.GW has held grants from the Canadian Institutes of Health Research and she is currently the recipient of a Research Early Career Award from Hamilton Health Sciences Foundation. MAZ is currently funded by the Wellcome Trust [217446/Z/19/Z] and the Biotechnology and Biological Sciences Research Council [BB/X511869/1]. RJdS has served as an external resource person to the WHO’s Nutrition Guidelines Advisory Group on trans fats, saturated fats and polyunsaturated fats. The WHO paid for his travel and accommodation to attend meetings from 2012 to 2017 to present and discuss this work. He has presented updates of this work to the WHO in 2022. He has also done contract research for the Canadian Institutes of Health Research’s Institute of Nutrition, Metabolism, and Diabetes, Health Canada, and the WHO for which he received remuneration. He has received speaker’s fees from the University of Toronto and McMaster Children’s Hospital. He has held grants from the Canadian Institutes of Health Research, Canadian Foundation for Dietetic Research, Population Health Research Institute and Hamilton Health Sciences Corporation as a principal investigator and is a coinvestigator on several funded team grants from the Canadian Institutes of Health Research. He has served as an independent director of the Helderleigh Foundation (Canada). He serves as a member of the Nutrition Science Advisory Committee to Health Canada (Government of Canada) and a co-opted member of the Scientific Advisory Committee on Nutrition (SACN) Subgroup on the Framework for the Evaluation of Evidence (Public Health England). All other authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To investigate the relationship between pain intensity and insomnia frequency in women with a diagnosis of deep endometriosis. The hypothesis is that these patients with moderate or severe pain have a higher frequency of insomnia than those with mild or no pain., Methods: We conducted a cross-sectional study of women with deep endometriosis categorized by pelvic pain intensity based on a numerical scale. Insomnia was assessed through a self-reported questionnaire, and multiple logistic regression was used to control for confounders between pain and insomnia., Results: We included 234 women in the study, 39 (17%) without pelvic pain; 66 (29%) with mild pain; 53 (23%) moderate pain; and 76 (32%) severe pain. Twenty-nine (74%) pain-free women and 50 (75%) with mild pain had no insomnia; only 3 (8%) of the former and 3 (4%) of the latter group had severe insomnia. However, twenty-nine (55%) women with moderate pain and 37 (48%) with severe pain had insomnia. The logistic regression model showed that moderate to severe pain increased insomnia 2.8 times, twice for every 10 years of pain duration, and twice in women with low education levels., Conclusions: Women with moderate or severe pain had a high frequency of insomnia, increasing management complexity in patients with deep endometriosis. Pain intensity, pain duration, and low education level increased the chance of insomnia in those patients., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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; P MD = 0.011) in addition trials and decreased body weight (MD: -0.96 kg; 95% CI: -1.78, -0.14 kg; P MD = 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)., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: A woman's food choices during pregnancy may be associated with her offspring's food choices. Several studies support an association between childhood sugary beverage (SB) consumption and poor cardiometabolic health. This study aimed to assess the association of maternal SB consumption during pregnancy and later, with her offspring's SB consumption in early infancy and childhood., Methods: A total of 1945 women and 1595 children participating in 3 Canadian studies reported SB consumption during pregnancy, at 2 years of age, and/or at school age (5 to 8 years old). Mother and offspring SB intakes were self-reported by mothers. Multivariable linear regression analyses were conducted within each cohort and cohort data were combined using fixed effect meta-analyses., Results: Maternal SB consumption during pregnancy was associated with higher offspring SB consumption at 2 years of age (standardized β = 0.19 predicted change in the number of standard deviations of offspring SB intake for an increase of 1 standard deviation in maternal serving [95% CI: 0.16 to 0.22]). Concurrent maternal SB consumption was associated with higher offspring SB intake when children were aged 5 to 8 years (standardized β= 0.25 [95% CI: 0.10 to 0.40])., Conclusion: Maternal SB consumption during pregnancy is associated with a marginally higher SB intake among their offspring at age 2, and concurrent maternal consumption is associated with a higher SB intake among school-aged offspring (5 to 8 years old). Future interventions tailored for pregnancy and early childrearing years to reduce SB intakes of mothers may reduce young children's SB intake., (© 2022. The Author(s) under exclusive license to The Canadian Public Health Association.)

Application methods of transcranial direct current stimulation (tDCS) in Parkinson's disease (PD) are quite divergent making it difficult to define the clinical effectiveness of the tDCS on PD. Thus, the aim of this study was to verify the acute effects of tDCS when applied to different targets (Cz or C3-Cz-C4) combined to physical therapy to improve balance and gait in individuals with PD. A randomized controlled trial was conducted, with 50 individuals who were separated into four groups: 1) Real tDCS (Cz) + physical therapy, 2) Real tDCS (C3-Cz-C4) + physical therapy, 3) Sham tDCS + physical therapy and 4) Educational lecture + physical therapy. The current intensity was 2 mA, applied for 20 min. For the instrumental assessment of balance and gait, the 3D motion analysis system was used. For the biomechanical analysis of gait, three different conditions were performed: normal gait, dual task gait and obstacle gait. For balance analysis, the following positions were utilized: Romberg with eyes opened, Romberg with eyes closed, Tandem with eyes opened and Tandem with eyes closed. All evaluations were performed pre-intervention, post-intervention (immediately at the end of the intervention) and were followed-up on (24 h after the end of the intervention). No statistically significant differences were found for all gait and balance outcomes when considering the interaction between time (pre, post and follow-up assessments) versus group (Education, Sham, Cz and C3-Cz-C4). In conclusion, it was found that one session of tDCS, stimulating Cz or C3-Cz-C4 combined with physical therapy, was not effective in improving the balance and gait in people with PD as compared to sham tDCS or educational lecture plus physiotherapy., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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 β-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 (R 2 = 0.109) and serum metabolome (R 2 = 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., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Osteoporosis has traditionally been characterized by underlying endocrine mechanisms, though evidence indicates a role of inflammation in its pathophysiology. Lipopolysaccharide (LPS), a component of gram-negative bacteria that reside in the intestines, can be released into circulation and stimulate the immune system, upregulating bone resorption. Exogenous LPS is used in rodent models to study the effect of systemic inflammation on bone, and to date a variety of different doses, routes, and durations of LPS administration have been used. The study objective was to determine whether systemic administration of LPS induced inflammatory bone loss in rodent models. A systematic search of Medline and four other databases resulted in a total of 110 studies that met the inclusion criteria. Pooled standardized mean differences (SMDs) and corresponding 95% confidence intervals (CI) with a random-effects meta-analyses were used for bone volume fraction (BV/TV) and volumetric bone mineral density (vBMD). Heterogeneity was quantified using the I 2 statistic. Shorter-term (<2 weeks) and longer-term (>2 weeks) LPS interventions were analyzed separately because of intractable study design differences. BV/TV was significantly reduced in both shorter-term (SMD = -3.79%, 95% CI [-4.20, -3.38], I 2 62%; p < 0.01) and longer-term (SMD = -1.50%, 95% CI [-2.00, -1.00], I 2 78%; p < 0.01) studies. vBMD was also reduced in both shorter-term (SMD = -3.11%, 95% CI [-3.78, -2.44]; I 2 72%; p < 0.01) and longer-term (SMD = -3.49%, 95% CI [-4.94, -2.04], I 2 82%; p < 0.01) studies. In both groups, regardless of duration, LPS negatively impacted trabecular bone structure but not cortical bone structure, and an upregulation in bone resorption demonstrated by bone cell staining and serum biomarkers was reported. This suggests systemically delivered exogenous LPS in rodents is a viable model for studying inflammatory bone loss, particularly in trabecular bone. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Objective: To implement a telerehabilitation prevention, treatment, and follow-up physical therapy protocol for monitoring individuals with Parkinson's disease (PD) and to verify its effectiveness in minimizing the deleterious effects of the COVID-19 pandemic., Design: Prospective case series, involving 40 participants with mild to moderate PD recruited from a specialized neurorehabilitation group. The study was divided into four parts: (1) Phone calls to assess the feasibility of participating in remote physical therapy. (2) Social media training. (3) Baseline and post-intervention assessment for functional lower extremity strength, fear of falling, quality of life, depression, anxiety, activities of daily living, verbal fluency. (4) Intervention protocol consisting of 20 remote weekly physical therapy sessions, graphic material for physical and cognitive training, social activities, and education., Conclusion: The telerehabilitation protocol was viable and effective for patients with PD as an alternative to in-person treatment during the COVID-19 pandemic., (Copyright © 2022 Natália Mariano Barboza, Hayslenne Andressa Gonçalves de Oliveira Araújo, Marcelle Brandão Terra, Maria Eduarda Brandão Bueno, Rogério José Souza, Andressa Letícia Miri, Suhaila Mahmoud Smaili.)

Background: The cardiovascular disease (CVD) burden among South Asians is high. Lifestyle interventions have been effective in the primary prevention of CVD, but this has not been replicated, through a synthesis of randomised trials, in South Asians., Methods: Four electronic databases (MEDLINE, Embase, CENTRAL and CINAHL), two clinical trial registries and references of included articles were searched through June 2022 (featuring ≥90% South Asian participants). Random-effects pairwise meta-analyses were performed, and heterogeneity was quantified with the I 2 statistic. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) framework was used to report on the quality of evidence (International Prospective Register of Systematic Reviews registration (PROSPERO)., Results: Thirty-five studies were included. Twelve tested diet and physical activity interventions; 18 tested diet alone; and 5 tested physical activity alone. All reported effects of the intervention(s) on at least one established risk factor for CVD, including blood pressure (systolic blood pressure (SBP), diastolic blood pressure (DBP) and blood lipids (high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc) or triglycerides). No trials reported clinical CVD. There is moderate-quality evidence that diet and physical activity interventions improve SBP (mean difference (MD) -2.72 mm Hg, 95% CI -4.11 to -1.33) and DBP (MD -1.53 mm Hg, 95% CI -2.57 to -0.48); high-quality to moderate-quality evidence that diet-only interventions improve DBP (MD -2.05 mm Hg, 95% CI -2.93 to -1.16) and blood lipids (triglycerides (MD -0.10 mmol/L, 95% CI -0.14 to -0.06) and LDLc (MD -0.19 mmol/L, 95% CI -0.32 to -0.06)); and moderate-quality evidence that physical activity-only interventions improve SBP (MD -9.7 mm Hg, 95% CI -11.05 to -8.35), DBP (MD -7.29 mm Hg, 95% CI -8.42 to -6.16) and HDLc (MD 0.08 mmol/L, 95% CI 0.04 to 0.11) compared with usual care., Conclusions: Lifestyle interventions improve blood pressure and blood lipid profiles in adult South Asians at risk of CVD. Tailored interventions should be used to modify cardiovascular risk factors in this at-risk group., Prospero Registration Number: CRD42018090419., Competing Interests: Competing interests: RJdS has served as an external resource person to the WHO’s Nutrition Guidelines Advisory Group on trans fats, saturated fats and polyunsaturated fats. The WHO paid for his travel and accommodation to attend meetings from 2012 to 2017 to present and discuss this work. He has also done contract research for the Canadian Institutes of Health Research’s Institute of Nutrition, Metabolism, and Diabetes, Health Canada and the WHO, for which he received remuneration. He has received speaker’s fees from the University of Toronto and McMaster Children’s Hospital. He serves as a member of the Nutrition Science Advisory Committee to Health Canada (government of Canada), a co-opted member of the Scientific Advisory Committee on Nutrition Subgroup on the Framework for the Evaluation of Evidence (Public Health England) and an independent director of the Helderleigh Foundation (Canada)., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: High cereal fiber and low-glycemic index (GI) diets are associated with reduced cardiovascular disease (CVD) risk in cohort studies. Clinical trial evidence on event incidence is lacking. Therefore, to make trial outcomes more directly relevant to CVD, we compared the effect on carotid plaque development in diabetes of a low-GI diet versus a whole-grain wheat-fiber diet., Research Design and Methods: The study randomized 169 men and women with well-controlled type 2 diabetes to counseling on a low GI-diet or whole-grain wheat-fiber diet for 3 years. Change in carotid vessel wall volume (VWV) (prespecified primary end point) was assessed by MRI as an indication of arterial damage., Results: Of 169 randomized participants, 134 completed the study. No treatment differences were seen in VWV. However, on the whole-grain wheat-fiber diet, VWV increased significantly from baseline, 23 mm3 (95% CI 4, 41; P = 0.016), but not on the low-GI diet, 8 mm3 (95% CI -10, 26; P = 0.381). The low-GI diet resulted in preservation of renal function, as estimated glomerular filtration rate, compared with the reduction following the wheat-fiber diet. HbA1c was modestly reduced over the first 9 months in the intention-to-treat analysis and extended with greater compliance to 15 months in the per-protocol analysis., Conclusions: Since the low-GI diet was similar to the whole-grain wheat-fiber diet recommended for cardiovascular risk reduction, the low-GI diet may also be effective for CVD risk reduction., (© 2022 by the American Diabetes Association.)

South Asian women are at increased risk of developing gestational diabetes mellitus (GDM). Few studies have investigated the genetic contributions to GDM risk. We investigated the association of a type 2 diabetes (T2D) polygenic risk score (PRS), on its own, and with GDM risk factors, on GDM-related traits using data from two birth cohorts in which South Asian women were enrolled during pregnancy. 837 and 4372 pregnant South Asian women from the SouTh Asian BiRth CohorT (START) and Born in Bradford (BiB) cohort studies underwent a 75-g glucose tolerance test. PRSs were derived using genome-wide association study results from an independent multi-ethnic study (~18% South Asians). Associations with fasting plasma glucose (FPG); 2 hr post-load glucose (2hG); area under the curve glucose; and GDM were tested using linear and logistic regressions. The population attributable fraction (PAF) of the PRS was calculated. Every 1 SD increase in the PRS was associated with a 0.085 mmol/L increase in FPG ([95% confidence interval, CI=0.07-0.10], p=2.85×10 -20 ); 0.21 mmol/L increase in 2hG ([95% CI=0.16-0.26], p=5.49×10 -16 ); and a 45% increase in the risk of GDM ([95% CI=32-60%], p=2.27×10 -14 ), independent of parental history of diabetes and other GDM risk factors. PRS tertile 3 accounted for 12.5% of the population's GDM alone, and 21.7% when combined with family history. A few weak PRS and GDM risk factors interactions modulating FPG and GDM were observed. Taken together, these results show that a T2D PRS and family history of diabetes are strongly and independently associated with multiple GDM-related traits in women of South Asian descent, an effect that could be modulated by other environmental factors., Competing Interests: AL, JL, KS, DD, BK, Rd, GP, JW, SA No competing interests declared, DL has received support from Medtronic Ltd and Roche Diagnostics for research unrelated to that presented here. No financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work, (© 2022, Lamri et al.)

Objectives: The study objective was to understand the barriers and facilitators to healthy active living in South Asian families living in Canada., Design: Semi-structured interviews of 30-60-minute duration with South Asian women with young families, and analysed using a thematic analytical approach., Setting: Community-dwelling South Asian women interviewed in the home environment or by phone., Participants: Fifteen married South Asian women (mean age=34.2 years) living in the Peel region of Ontario, Canada, with at least 1 child under the age of 5 years. The majority of women had immigrated to Canada (13/15), during a 5-10-year interval preceding interviews., Results: 57 different codes were derived from 18 interview hours, and further evaluated through member checking. The top three barriers to healthy eating were: (1) not having enough time for healthy food preparation, (2) lack of knowledge about what is healthy eating and (3) viewing healthy eating as a matter of engaging in time limited dieting. These barriers were addressed with: (1) knowledge and awareness of healthy eating, (2) clear goal setting, (3) access to fresh vegetables and fruits and (4) better arrangements and more time for food preparation. The top five barriers to physical activity were: (1) not enough time and energy, (2) competing priorities, (3) lack of childcare, (4) lack of family-engaging exercise and (5) limited access to interesting exercise programming. These barriers were addressed by: (1) experiencing exercise as enjoyable and stress releasing, (2) commitments to walking exercise, (3) use of an electronic exercise-tracking device, (4) offspring exercise supported by spouse and family and (5) success stories about exercise from others., Conclusions: Barriers to healthy active living in South Asian women with young families can be addressed with facilitators that stimulate clear goal setting and healthy food preparation skills, and exercise formats that engage mothers and offspring, with or without exercise tracking., Competing Interests: Competing interests: RJD has served as an external resource person to the World Health Organization’s Nutrition Guidelines Advisory Group on trans fats, saturated fats, and polyunsaturated fats. The WHO paid for his travel and accommodation to attend meetings from 2012-2017 to present and discuss this work. He has presented updates of this work to the WHO in 2022. He has also done contract research for the Canadian Institutes of Health Research’s Institute of Nutrition, Metabolism, and Diabetes, Health Canada, and the World Health Organization for which he received remuneration. He has received speaker’s fees from the University of Toronto, and McMaster Children’s Hospital. He has held grants from the Canadian Institutes of Health Research, Canadian Foundation for Dietetic Research, Population Health Research Institute, and Hamilton Health Sciences Corporation as a principal investigator, and is a co-investigator on several funded team grants from the Canadian Institutes of Health Research. He has served as an independent director of the Helderleigh Foundation (Canada). He serves as a member of the Nutrition Science Advisory Committee to Health Canada (Government of Canada), and a co-opted member of the Scientific Advisory Committee on Nutrition (SACN) Subgroup on the Framework for the Evaluation of Evidence (Public Health England).PR is currently funded by the Canadian Institutes of Health (2021–2025). He coordinates research with NexJ Health, which provides a software platform to convey the psychosocial and psychiatric programming he develops and assesses. He receives no personal compensations for studies coordinated with NexJ but does receive free-of-charge platform support. All other authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Implantable cardioverter defibrillators (ICDs) are an adjunct to guideline-directed medical therapy for heart failure with reduced ejection fraction. The uptake of sacubitril/valsartan in this population is not well described. We report the uptake and factors associated with sacubitril/valsartan use in patients with left ventricular dysfunction undergoing ICD implantation., Methods: A retrospective chart review was performed on all patients with left ventricular dysfunction who underwent de novo primary prevention ICD implantation between October 2015 and December 2021 (n = 422) at Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. Pre-procedure sacubitril/valsartan use was determined. Logistic regression analysis was performed to examine factors associated with sacubitril/valsartan use. A Bayesian estimator of abrupt change was employed to determine a time period in which a change in the rate of sacubitril/valsartan use occurred., Results: Loop diuretic use (odds ratio [OR] = 2.20) and higher severity of New York Heart Association class symptoms (OR = 1.62) were associated with sacubitril/valsartan use. Sacubitril/valsartan use increased during the study period, to 59% in December 2021. This increase was larger among those aged ≥ 65 years (OR = 1.09). A change in the rate of sacubitril/valsartan use occurred 3 years after drug approval, 1 year after provincial drug coverage became available, and 6 months after being strongly recommended in clinical guidelines., Conclusions: In a contemporary cohort of ICD patients, sacubitril/valsartan use increased between 2015 and 2021, notably in those aged ≥ 65 years and after government drug coverage became available. Understanding barriers to sacubitril/valsartan use in ICD patients is recommended to improve clinical outcomes and survival in this population., (© 2022 The Authors.)

This systematic review and meta-analysis aimed to investigate the effect of dietary-based lifestyle modification interventions ("diet," or "diet + exercise," or "diet + exercise + behavioral" intervention) on the measures of anthropometric and dietary intake parameters in women with breas cancer (BC). Databases were searched until June 2021. Inclusion criteria were randomized controlled trials that enrolled only women with BC. Studies that used exercise or behavioral interventions alone were not included. Mean ± SD changes were extracted for each outcome, and pooled using a random-effects model; 7315 studies were identified. Fifty-one studies (n = 7743) were included. The median ± SD duration of treatment was 24 ± 16.65 wk. Dietary-based interventions significantly reduced body weight [45 studies (n = 7239), weighted mean difference (WMD) (95% CI): -2.6 (-3.2, -2.1) kg], BMI [31 studies (n = 5384); WMD (95% CI): -1.0 (-1.3, -0.7) kg/m2], lean body mass [15 studies (n = 1194); WMD (95% CI): -0.6(-0.7, -0.4) kg], fat mass [11 studies (n = 913); WMD (95% CI): -2.6 (-3.3, -1.8) kg], fat percentage [17 studies (n = 897); WMD (95% CI): -1.5 (-1.9, -1.3)%], hip circumference [9 studies (n = 489); WMD (95% CI): -2.43 (-3.34, -1.54) cm], and waist circumference [7 studies (n = 309); WMD (95% CI): 0.02 (-0.03, -0.005) cm]. Significant reductions in energy intakes [20 studies (n = 4608), WMD (95% CI): -162 (-220, 104) kcal/d] and fat intakes [7 studies (n = 4316), WMD (95% CI): -7.5 (-7.8, -7.2)% of energy/d], and an increase in fiber intakes [11 studies (n = 4241), WMD (95% CI): 2.4 (0.7, 4.1) g/d] were observed. No significant changes were seen in protein, carbohydrate, and fruit and vegetable intakes. Subgroup analyses showed that changes in anthropometric and dietary intake indices were significant in studies that enrolled patients with both obesity and normal weight, studies that used diet therapy in combination with exercise and behavioral therapy, and studies that started the intervention during the treatment period. Overall, a multimodal dietary-based lifestyle intervention had significant effects on anthropometric and dietary intake parameters in women with BC, specifically when started as early as the diagnosis. This meta-analysis was registered at PROSPERO as CRD42021291488., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)