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Background: Disparities in colorectal cancer screening have been documented among people with intellectual and developmental disabilities (IDD). However, surgical outcomes in this population have yet to be studied. The present work aimed to evaluate the association of IDD with outcomes following colorectal cancer resection., Methods: All adults undergoing resection for colorectal cancer in the 2011-2020 National Inpatient Sample were identified. Multivariable linear and logistic regression models were developed to examine the association of IDD with risk factors as well as outcomes including mortality, complications, costs, length of stay (LOS), and non-home discharge. The study is limited by its retrospective nature and did not capture disease staging or time of diagnosis., Results: Among 722,736 patients undergoing colorectal cancer resection, 2,846 (0.39%) had IDD. Compared to patients without IDD, IDD patients were younger and had a higher burden of comorbidities. IDD status was associated with increased odds of non-elective admission (AOR 1.40 [95% CI 1.14-1.73]) and decreased odds of treatment at high-volume centers (AOR 0.64 [95% CI 0.51-0.81]). Furthermore, IDD patients experienced significantly greater LOS (9 vs 6 days, p<0.001) and hospitalization costs ($23,500 vs $19,800, p<0.001) relative to neurotypical patients. Upon risk adjustment, IDD was significantly associated with 2-fold increased odds of mortality (AOR 2.34 [95% CI 1.48-3.71]), 1.4-fold increase in complications (AOR 1.41 [95% CI 1.15-1.74]), and 6.8-fold increase in non-home discharge (AOR 6.83 [95% CI 5.46-8.56])., Conclusions: IDD patients undergoing colorectal cancer resection experience increased likelihood of non-elective admission, adverse clinical outcomes, and resource use. Our findings highlight the need for more accessible screening and patient-centered interventions to improve quality of surgical care for this at-risk population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ng 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.)

Alzheimer's disease is the leading cause of dementia worldwide, but the cellular pathways that underlie its pathological progression across brain regions remain poorly understood 1-3 . Here we report a single-cell transcriptomic atlas of six different brain regions in the aged human brain, covering 1.3 million cells from 283 post-mortem human brain samples across 48 individuals with and without Alzheimer's disease. We identify 76 cell types, including region-specific subtypes of astrocytes and excitatory neurons and an inhibitory interneuron population unique to the thalamus and distinct from canonical inhibitory subclasses. We identify vulnerable populations of excitatory and inhibitory neurons that are depleted in specific brain regions in Alzheimer's disease, and provide evidence that the Reelin signalling pathway is involved in modulating the vulnerability of these neurons. We develop a scalable method for discovering gene modules, which we use to identify cell-type-specific and region-specific modules that are altered in Alzheimer's disease and to annotate transcriptomic differences associated with diverse pathological variables. We identify an astrocyte program that is associated with cognitive resilience to Alzheimer's disease pathology, tying choline metabolism and polyamine biosynthesis in astrocytes to preserved cognitive function late in life. Together, our study develops a regional atlas of the ageing human brain and provides insights into cellular vulnerability, response and resilience to Alzheimer's disease pathology., (© 2024. The Author(s).)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Esophagectomy is a complex oncologic operation associated with high rates of postoperative complications. While respiratory and septic complications have been well-defined, the implications of acute kidney injury (AKI) remain unclear. Using a nationally representative database, we aimed to characterize the association of AKI with mortality, resource use, and 30-day readmission., Methods: All adults undergoing elective esophagectomy with a diagnosis of esophageal or gastric cancer were identified in the 2010-2019 Nationwide Readmissions Database. Study cohorts were stratified based on presence of AKI. Multivariable regressions and Royston-Parmar survival analysis were used to evaluate the independent association between AKI and outcomes of interest., Results: Of an estimated 40,438 patients, 3,210 (7.9%) developed AKI. Over the 10-year study period, the incidence of AKI increased from 6.4% to 9.7%. Prior radiation/chemotherapy and minimally invasive operations were associated with reduced odds of AKI, whereas public insurance coverage and concurrent infectious and respiratory complications had greater risk of AKI. After risk adjustment, AKI remained independently associated with greater odds of in-hospital mortality (AOR: 4.59, 95% CI: 3.62-5.83) and had significantly increased attributable costs ($112,000 vs $54,000) and length of stay (25.7 vs 13.3 days) compared to patients without AKI. Furthermore, AKI demonstrated significantly increased hazard of 30-day readmission (hazard ratio: 1.16, 95% CI: 1.01-1.32)., Conclusions: AKI after esophagectomy is associated with greater risk of mortality, hospitalization costs, and 30-day readmission. Given the significant adverse consequences of AKI, careful perioperative management to mitigate this complication may improve quality of esophageal surgical care at the national level., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ng 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: The COVID-19 pandemic impacted mental health disorders, affecting both individuals with pre-existing conditions and those with no prior history. However, there is limited evidence regarding the pandemic's impact on mental health visits to primary care physicians. The International Consortium of Primary Care Big Data Researchers (INTRePID) explored primary care visit trends related to mental health conditions in Argentina, Australia, Canada, China, Norway, Peru, Singapore, Sweden, and the USA., Methods: We conducted an interrupted time series analysis in nine countries to examine changes in rates of monthly mental health visits to primary care settings from January 1st, 2018, to December 31st, 2021. Sub-group analysis considered service type (in-person/virtual) and six categories of mental health conditions (anxiety/depression, bipolar/schizophrenia/other psychotic disorders, sleep disorders, dementia, ADHD/eating disorders, and substance use disorder)., Findings: Mental health visit rates increased after the onset of the pandemic in most countries. In Argentina, Canada, China, Norway, Peru, and Singapore, this increase was immediate ranged from an incidence rate ratio of 1·118 [95% CI 1.053-1.187] to 2.240 [95% CI 2.057-2.439] when comparing the first month of pandemic with the pre-pandemic trend. Increases in the following months varied across countries. Anxiety/depression was the leading reason for mental health visits in most countries. Virtual visits were reported in Australia, Canada, Norway, Peru, Sweden, and the USA, accounting for up to 40% of the total mental health visits., Interpretation: Findings suggest an overall increase in mental health visits, driven largely by anxiety/depression. During the COVID-19 pandemic, many of the studied countries adopted virtual care in particular for mental health visits. Primary care plays a crucial role in addressing mental ill-health in times of crisis., Funding: Canadian Institutes of Health Research grant #173094 and the Rathlyn Foundation Primary Care EMR Research and Discovery Fund., Competing Interests: CL and AO receive a salary for research associate positions at the University of Toronto. JMW holds the position of Vice President Medical Affairs and is employed by the DARTNet Institute. SdeL serves as the director of the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) the primary care sentinel network and he receives funding from the UK Health Security Agency for this position. Seqirus and Roche provided a bursary for speaking. AstraZeneca provided a bursary to attend a European conference. Additionally, AstraZeneca, Sanofi, and Seqirus provided funding for Advisory Board membership. RSK has received payment from Qulturum Jönköping County for lectures and support from Region Uppsala to attend WONCA Sydney 2023. MSC-F is an Associate Professor at the Universidad Peruana Cayetano Heredia, and the Director of the Primary Health Care Research Center. Her salary is sourced from teaching, contracts and grants awarded to the university. She has received a grant from the National Council of Science and Technology of Peru. KT receives a Chair in Family and Community Medicine Research in Primary Care at UHN. She has received grants from the following organizations in the past 3 years: The Canadian Institutes of Health Research, Rathlyn Foundation Primary Care EMR Research and Discovery Fund, College of Family Physicians of Canada/Foundation for Advancing Family Medicine/CMA Foundation Heart and Stroke Foundation of Ontario, Department of Defense United States of America, St. Michael's Hospital Foundation, Ontario Health Data Platform First Movers Fund, Queen's University CSPC Research Initiation Grant, Diabetes Canada, Heart and Stroke Foundation and Brain Canada Heart-Brain IMPACT Award, CANSSI ICES Data Access Grant, North York General Hospital Exploration Fund, CFPC Janus Grant. Support for attending meetings is provided by the Rathlyn Foundation Primary Care EMR Research and Discovery Fund. None of the other authors have reported any other potential conflicts of interest., (© 2024 The Author(s).)

Philadelphia chromosome-positive B cell acute lymphoblastic leukemia (B-ALL), characterized by the BCR::ABL1 fusion gene, remains a poor prognosis cancer needing new therapeutic approaches. Transcriptomic profiling identified up-regulation of oncogenic transcription factors ERG and c-MYC in BCR::ABL1 B-ALL with ERG and c-MYC required for BCR::ABL1 B-ALL in murine and human models. Profiling of ERG- and c-MYC-dependent gene expression and analysis of ChIP-seq data established ERG and c-MYC coordinate a regulatory network in BCR::ABL1 B-ALL that controls expression of genes involved in several biological processes. Prominent was control of ribosome biogenesis, including expression of RNA polymerase I (POL I) subunits, the importance of which was validated by inhibition of BCR::ABL1 cells by POL I inhibitors, including CX-5461, that prevents promoter recruitment and transcription initiation by POL I. Our results reveal an essential ERG- and c-MYC-dependent transcriptional network involved in regulation of metabolic and ribosome biogenesis pathways in BCR::ABL1 B-ALL, from which previously unidentified vulnerabilities and therapeutic targets may emerge.

Objectives In this overview, we describe theObservational Medical Outcomes Partnership Common Data Model (OMOP-CDM), the established governance processes employed in EMR data repositories, and demonstrate how OMOP transformed data provides a lever for more efficient and secure access to electronic medical record (EMR) data by health service providers and researchers. Methods Through pseudonymisation and common data quality assessments, the OMOP-CDM provides a robust framework for converting complex EMR data into a standardised format. This allows for the creation of shared end-to-end analysis packages without the need for direct data exchange, thereby enhancing data security and privacy. By securely sharing de-identified and aggregated data and conducting analyses across multiple OMOP-converted databases, patient-level data is securely firewalled within its respective local site. Results By simplifying data management processes and governance, and through the promotion of interoperability, the OMOP-CDM supports a wide range of clinical, epidemiological, and translational research projects, as well as health service operational reporting. Discussion Adoption of the OMOP-CDM internationally and locally enables conversion of vast amounts of complex, and heterogeneous EMR data into a standardised structured data model, simplifies governance processes, and facilitates rapid repeatable cross-institution analysis through shared end-to-end analysis packages, without the sharing of data. Conclusion The adoption of the OMOP-CDM has the potential to transform health data analytics by providing a common platform for analysing EMR data across diverse healthcare settings., 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.)

Competing Interests: Paul G. Ekert and Seong L. Khaw are recipients of a share in milestone and royalty payments paid to the Walter and Eliza Hall Institute of Medical Research for the development of venetoclax.

Background: Racial disparities in access to preoperative evaluation for colorectal cancer remain unclear. Emergent admission may indicate lack of access to timely care. The present work aimed to evaluate the association of admission type with race among patients undergoing colorectal cancer surgery., Methods: All adults undergoing resection for colorectal cancer in 2011-2020 National Inpatient Sample were identified. Multivariable regression models were developed to examine the association of admission type with race. Primary outcome was major adverse events (MAE), including mortality and complications. Secondary outcomes included costs and length of stay (LOS). Interaction terms between year, admission type, and race were used to analyze trends., Results: Of 722,736 patients, 67.6 % had Elective and 32.4 % Emergent admission. Black (AOR 1.38 [95 % CI 1.33-1.44]), Hispanic (1.45 [1.38-1.53]), and Asian/Pacific Islander or Native American (1.25 [1.18-1.32]) race were associated with significantly increased odds of Emergent operation relative to White. Over the study period, non-White patients consistently comprised over 5 % greater proportion of the Emergent cohort compared to Elective. Furthermore, Emergent admission was associated with 3-fold increase in mortality and complications, 5-day increment in LOS, and $10,100 increase in costs. MAE rates among Emergent patients remained greater than Elective with a widening gap over time. Non-White patients experienced significantly increased MAE regardless of admission type., Conclusion: Non-White race was associated with increased odds of emergent colorectal cancer resection. Given the persistent disparity over the past decade, systematic approaches to alleviate racial inequities in colorectal cancer screening and improve access to timely surgical treatment are warranted., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s).)

Across the globe, 2-3% of humans carry the p.Ser132Pro single nucleotide polymorphism in MLKL, the terminal effector protein of the inflammatory form of programmed cell death, necroptosis. Here we show that this substitution confers a gain in necroptotic function in human cells, with more rapid accumulation of activated MLKL S132P in biological membranes and MLKL S132P overriding pharmacological and endogenous inhibition of MLKL. In mouse cells, the equivalent Mlkl S131P mutation confers a gene dosage dependent reduction in sensitivity to TNF-induced necroptosis in both hematopoietic and non-hematopoietic cells, but enhanced sensitivity to IFN-β induced death in non-hematopoietic cells. In vivo, Mlkl S131P homozygosity reduces the capacity to clear Salmonella from major organs and retards recovery of hematopoietic stem cells. Thus, by dysregulating necroptosis, the S131P substitution impairs the return to homeostasis after systemic challenge. Present day carriers of the MLKL S132P polymorphism may be the key to understanding how MLKL and necroptosis modulate the progression of complex polygenic human disease., (© 2023. Springer Nature Limited.)

Altered microglial states affect neuroinflammation, neurodegeneration, and disease but remain poorly understood. Here, we report 194,000 single-nucleus microglial transcriptomes and epigenomes across 443 human subjects and diverse Alzheimer's disease (AD) pathological phenotypes. We annotate 12 microglial transcriptional states, including AD-dysregulated homeostatic, inflammatory, and lipid-processing states. We identify 1,542 AD-differentially-expressed genes, including both microglia-state-specific and disease-stage-specific alterations. By integrating epigenomic, transcriptomic, and motif information, we infer upstream regulators of microglial cell states, gene-regulatory networks, enhancer-gene links, and transcription-factor-driven microglial state transitions. We demonstrate that ectopic expression of our predicted homeostatic-state activators induces homeostatic features in human iPSC-derived microglia-like cells, while inhibiting activators of inflammation can block inflammatory progression. Lastly, we pinpoint the expression of AD-risk genes in microglial states and differential expression of AD-risk genes and their regulators during AD progression. Overall, we provide insights underlying microglial states, including state-specific and AD-stage-specific microglial alterations at unprecedented resolution., Competing Interests: Declaration of interests L.-H.T. is a member of the Scientific Advisory Board of Cognito Therapeutics, 4M Therapeutics, Cell Signaling Technology, and Souvien Therapeutics, which has no association to this study., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) is the most common cause of dementia worldwide, but the molecular and cellular mechanisms underlying cognitive impairment remain poorly understood. To address this, we generated a single-cell transcriptomic atlas of the aged human prefrontal cortex covering 2.3 million cells from postmortem human brain samples of 427 individuals with varying degrees of AD pathology and cognitive impairment. Our analyses identified AD-pathology-associated alterations shared between excitatory neuron subtypes, revealed a coordinated increase of the cohesin complex and DNA damage response factors in excitatory neurons and in oligodendrocytes, and uncovered genes and pathways associated with high cognitive function, dementia, and resilience to AD pathology. Furthermore, we identified selectively vulnerable somatostatin inhibitory neuron subtypes depleted in AD, discovered two distinct groups of inhibitory neurons that were more abundant in individuals with preserved high cognitive function late in life, and uncovered a link between inhibitory neurons and resilience to AD pathology., Competing Interests: Declaration of interests L.-H.T. is a member of the Scientific Advisory Boards of Cognito Therapeutics, 4M Therapeutics, Cell Signaling Technology, and Souvien Therapeutics, which have no association to the work described in this manuscript., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To test whether adherence to the Mediterranean diet, the Dietary Approaches to Stop Hypertension (DASH) or a dietary pattern in-line with the 2015-2020 Dietary Guidelines for Americans (DGA) was associated with obesity., Design: 24-h dietary recall data from the Canadian Community Health Survey (CCHS)-Nutrition, 2004 and 2015 cycles, were analysed. Diet quality index scores were computed for the Mediterranean-Style Dietary Pattern Score (MSDPS), a DASH index and the 2015 Dietary Guidelines for Americans Adherence Index (DGAI). Higher scores indicated greater adherence. Association between scores and obesity was examined using logistic regression, adjusting for age, sex, physical activity, smoking status, sequence of dietary recall and alcohol and energy intake., Setting: Canada (excluding territories and the institutionalised population)., Participants: Canadian adults (≥ 18 years), non-pregnant and non-breast-feeding; 11 748 from CCHS 2004 and 12 110 from CCHS 2015. The percentage of females in each sample was 50 %., Results: Mean MSDPS, DASH and DGAI scores were marginally but significantly higher in CCHS 2015 than in CCHS 2004. Those affected by obesity obtained lower scores for all indexes in CCHS 2004 (OR 10th v . 90th percentile for DASH: 2·23 (95 % CI 1·50, 3·32), DGAI: 3·01 (95 % CI 1·98, 4·57), MSDPS: 2·02 (95 % CI 1·14, 3·58)). Similar results were observed in CCHS 2015; however, results for MSDPS were not significant (OR 10th v . 90th percentile for DASH: 2·45 (95 % CI 1·72, 3·49), DGAI: 2·73 (95 % CI 1·85, 4·03); MSDPS: 1·30 (95 % CI 0·82, 2·06))., Conclusion: Following DASH or the 2015-2020 DGA was associated with a lower likelihood of obesity. Findings do not indicate causation, as the data are cross-sectional.

Polycythemia vera (PV) is a myeloproliferative neoplasm driven by activating mutations in JAK2 that result in unrestrained erythrocyte production, increasing patients' hematocrit and hemoglobin concentrations, placing them at risk of life-threatening thrombotic events. Our genome-wide association study of 440 PV cases and 403 351 controls using UK Biobank data showed that single nucleotide polymorphisms in HFE known to cause hemochromatosis are highly associated with PV diagnosis, linking iron regulation to PV. Analysis of the FinnGen dataset independently confirmed overrepresentation of homozygous HFE variants in patients with PV. HFE influences the expression of hepcidin, the master regulator of systemic iron homeostasis. Through genetic dissection of mouse models of PV, we show that the PV erythroid phenotype is directly linked to hepcidin expression: endogenous hepcidin upregulation alleviates erythroid disease whereas hepcidin ablation worsens it. Furthermore, we demonstrate that in PV, hepcidin is not regulated by expanded erythropoiesis but is likely governed by inflammatory cytokines signaling via GP130-coupled receptors. These findings have important implications for understanding the pathophysiology of PV and offer new therapeutic strategies for this disease., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Introduction: Canada promulgated mandatory front-of-pack labelling (FOPL) regulations in 2022, requiring pre-packaged foods meeting and/or exceeding recommended thresholds for nutrients-of-concern (i.e., saturated fat, sodium, sugars) to display a "high-in" nutrition symbol. However, there is limited evidence on how Canadian FOPL (CAN-FOPL) regulations compare to other FOPL systems and dietary guidelines. Therefore, the objectives of the study were to examine the diet quality of Canadians using the CAN-FOPL dietary index system and its alignment with other FOPL systems and dietary guidelines., Methods: Nationally representative dietary data from the 2015 Canadian Community Health Survey-Nutrition survey ( n  = 13,495) was assigned dietary index scores that underpin CAN-FOPL, Diabetes Canada Clinical Practice (DCCP) Guidelines, Nutri-score, Dietary Approaches to Stop Hypertension (DASH) and Canada's Food Guide (Healthy Eating Food Index-2019 [HEFI-2019]). Diet quality was examined by assessing linear trends of nutrient intakes across quintile groups of CAN-FOPL dietary index scores. The alignment of CAN-FOPL dietary index system compared with other dietary index systems, with HEFI as the reference standard, was examined using Pearson's correlations and к statistics., Results: The mean [95% CI] dietary index scores (range: 0-100) for CAN-FOPL, DCCP, Nutri-score, DASH, and HEFI-2019 were 73.0 [72.8, 73.2], 64.2 [64.0, 64.3], 54.9 [54.7, 55.1], 51.7 [51.4, 51.9], and 54.3 [54.1, 54.6], respectively. Moving from the "least healthy" to the "most healthy" quintile in the CAN-FOPL dietary index system, intakes of protein, fiber, vitamin A, vitamin C, and potassium increased, while intakes of energy, saturated fat, total and free sugars, and sodium decreased. CAN-FOPL showed moderate association with DCCP ( r  = 0.545, p  < 0.001), Nutri-score ( r  = 0.444, p  < 0.001),  and HEFI-2019 ( r  = 0.401, p  < 0.001), but poor association with DASH ( r  = 0.242, p  < 0.001). Slight to fair agreement was seen between quintile combinations of CAN-FOPL and all dietary index scores ( к  = 0.05-0.38)., Discussion: Our findings show that CAN-FOPL rates the dietary quality of Canadian adults to be healthier than other systems. The disagreement between CAN-FOPL with other systems suggest a need to provide additional guidance to help Canadians select and consume 'healthier' options among foods that would not display a front-of-pack nutrition symbol., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lee, Ahmed, Julia, Ng, Paper, Lou and L’Abbé.)

Background: Sociodemographic disparities in atrial fibrillation (AF) management and thromboembolic prophylaxis have previously been reported, which may involve inequitable access to left atrial appendage occlusion (LAAO) during cardiac surgery. The present study aimed to evaluate the association of LAAO utilization with sex, race, and hospital region among patients with AF undergoing heart valve operations., Methods: Adults with AF undergoing valve replacement/repair in the 2012-2019 National Inpatient Sample were identified and stratified based on concurrent LAAO. Multivariable linear and logistic regressions were developed to identify factors associated with LAAO utilization. Mortality, complications including stroke and thromboembolism, hospitalization costs and length of stay (LOS) were secondarily assessed., Results: Of 382,580 patients undergoing valve operations, 18.7% underwent concomitant LAAO. Over the study period, the proportion of female patients receiving LAAO significantly decreased from 44.8% to 38.9% (p<0.001). Upon risk adjustment, female (AOR 0.93 [95% CI 0.89-0.97]) and Black patients (0.91 [0.83-0.99]) had significantly reduced odds of undergoing LAAO compared to males and Whites, respectively. Additionally, hospitals in the Midwest (1.38 [1.24-1.51]) and West (1.26 [1.15-1.36]) had increased likelihood of LAAO whereas Northeast hospitals (0.85 [0.77-0.94)] had decreased odds relative to the South. Furthermore, LAAO was associated with decreased stroke (0.71 [0.60-0.84]) and thromboembolism (0.68 [0.54-0.86]), $4,200 reduction in costs and 1-day decrement in LOS., Conclusions: Female and Black patients had significantly lower odds while Midwest and Western hospitals had greater odds of LAAO utilization. Enhancing access to LAAO during valvular surgery is warranted to improve clinical and financial outcomes for patients with AF., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ng 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.)

Canada recently mandated front-of-pack (FOP) labelling regulations, where foods meeting and/or exceeding recommended thresholds for nutrients-of-concern (i.e., saturated fat, sodium, and sugars) must display a 'high-in' FOP nutrition symbol. However, there is limited research on the amounts and sources of foods consumed by Canadians that would require a FOP symbol. The objective was to examine the intakes of nutrients-of-concern from foods that would display a FOP symbol and to identify the top food categories contributing to intakes for each nutrient-of-concern. Using the first day 24-hour dietary recall from the nationally representative 2015 Canadian Community Health Survey-Nutrition (CCHS), Canadian adults' intakes of nutrients-of-concern from foods that would display a FOP symbol was examined. Foods were assigned to 1 of 62 categories to identify the top food categories contributing to intakes of energy and nutrient-of-concern that would display a FOP symbol for each nutrient-of-concern. Canadian adults (n = 13,495) consumed approximately 24% of total calories from foods that would display a FOP symbol. Foods that would display a FOP symbol for exceeding thresholds for nutrients-of-concern accounted for 16% of saturated fat, 30% of sodium, 25% of total sugar, and 39% of free sugar intakes among Canadian adults. The top food category contributing intakes of each nutrient-of-concern that would display a FOP symbol were nutrient-specific: Processed meat and meat substitutes for saturated fat; Breads for sodium; and Fruit juices & drinks for total and free sugars. Our findings show that Canadian FOP labelling regulations have the potential to influence the intakes of nutrients-of-concern for Canadian adults. Using the findings as baseline data, future studies are warranted to evaluate the impact of FOP labelling regulations., Competing Interests: MA, APN, and MRL received a competitive research grant from the Institute for the Advancement of Food and Nutrition Sciences (IAFNS) to analyze National Health and Nutrition Examination Survey (NHANES) data to determine sodium intakes and sources in diets of Americans. APN currently works at the Canadian Sugar Institute. However, none of the organizations had a role in this research. No other authors have competing interests to declare., (Copyright: © 2023 Lee 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 Guidelines for choice of prosthetic heart valve in people of reproductive age are not well established. Although biologic heart valves (BHVs) have risk of deterioration, mechanical heart valves (MHVs) require lifelong anticoagulation. This study aimed to characterize the association of prosthetic valve type with maternal and fetal outcomes in pregnant patients. Methods and Results Using the 2008 to 2019 National Inpatient Sample, we identified all adult patients hospitalized for delivery with prior heart valve implantation. Multivariable regressions were used to analyze the primary outcome, major adverse cardiovascular events, and secondary outcomes, including maternal and fetal complications, length of stay, and costs. Among 39 871 862 birth hospitalizations, 4152 had MHVs and 874 had BHVs. Age, comorbidities, and cesarean birth rates were similar between patients with MHVs and BHVs. The presence of a prosthetic valve was associated with over 22-fold increase in likelihood of major adverse cardiovascular events (MHV: adjusted odds ratio, 22.1 [95% CI, 17.3-28.2]; BHV: adjusted odds ratio, 22.5 [95% CI, 13.9-36.5]) as well as increased duration of stay and hospitalization costs. However, patients with MHVs and BHVs had no significant difference in the odds of any maternal outcome, including major adverse cardiovascular events, hypertensive disease of pregnancy, and ante/postpartum hemorrhage. Similarly, fetal complications were more likely in patients with valve prostheses, including a 4-fold increase in odds of stillbirth, but remained comparable between MHVs and BHVs. Conclusions Patients hospitalized for delivery with prior valve replacement carry substantial risk of adverse maternal and fetal events, regardless of valve type. Our findings reveal comparable outcomes between MHVs and BHVs.

Background: Cardiovascular diseases (CVDs) are the second leading cause of total deaths in Canada. High blood pressure is the main metabolic risk factor for developing CVDs. It has been well established that excess consumption of sodium adversely affects blood pressure. Canadians' mean sodium intakes are well above recommended levels. Reducing dietary sodium intake through food reformulation has been identified as a cost-effective intervention, however, dietary sodium intake and the potential health impact of meeting recommended sodium intake levels due to food reformulation have not been determined in Canada., Objective: This study aimed to 1) obtain robust estimates of Canadians' usual sodium intakes, 2) model sodium intakes had foods been reformulated to align with Health Canada's sodium reduction targets, and 3) estimate the number of CVD deaths that could be averted or delayed if Canadian adults were to reduce their mean sodium intake to recommended levels under three scenarios: A) 2,300 mg/d-driven by a reduction of sodium levels in packaged foods to meet Health Canada targets (reformulation); B) 2,000 mg/d to meet the World Health Organization (WHO) recommendation; and C) 1,500 mg/d to meet the Adequate Intake recommendation., Methods: Foods in the University of Toronto's Food Label Information Program 2017, a Canadian branded food composition database, were linked to nationally representative food intake data from the 2015 Canadian Community Health Survey-Nutrition to estimate sodium intakes (and intakes had Health Canada's reformulation strategy been fully implemented). The Preventable Risk Integrated ModEl (PRIME) was used to estimate potential health impact., Results: Overall, mean sodium intake was 2758 mg/day, varying by age and sex group. Based on 'reformulation' scenario A, mean sodium intakes were reduced by 459 mg/day, to 2299 mg/day. Reducing Canadians' sodium intake to recommended levels under scenarios A, B and C could have averted or delayed 2,176 (95% UI 869-3,687), 3,252 (95% UI 1,380-5,321), and 5,296 (95% UI 2,190-8,311) deaths due to CVDs, respectively, mainly from ischaemic heart disease, stroke, and hypertensive disease. This represents 3.7%, 5.6%, and 9.1%, respectively, of the total number of CVDs deaths observed in Canada in 2019., Conclusion: Results suggest that reducing sodium intake to recommended levels could prevent or postpone a substantial number of CVD deaths in Canada. Reduced sodium intakes could be achieved through reformulation of the Canadian food supply. However, it will require higher compliance from the food industry to achieve Health Canada's voluntary benchmark sodium reduction targets., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Flexner 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.)