Five-Year Serial Brain MRI Analysis of Military Members Exposed to Chronic Sub-Concussive Overpressures.

BACKGROUND: The Canadian Special Operations Forces Command conducts explosives operations and training which exposes members to explosive charges at close proximity. This 5-year longitudinal trial was conducted in follow-up to our initial trial which examined military breachers with MRI and EEG pre and post blast exposure. PURPOSE: To examine brain MRI findings in military personnel exposed to multiple repeated blast exposures. STUDY TYPE: Five-year longitudinal prospective trial. POPULATION: Ninety-two males aged 23-42 with an average of 9.4 years of blast exposure. FIELD STRENGTH/SEQUENCE: 3 T brain MRI/T1-weighted 3D with reconstruction in three planes, T2-weighted, T2-weighted fluid attenuated inversion recovery (FLAIR) 3D with reconstruction in three planes, T2-weighted gradient spin echo (GRE), saturation weighted images, DWI and ADC maps, diffusion tensor imaging. ASSESSMENT: All MRI scans were interpreted by the two neuroradiologists and one neuroradiology Fellow in a blinded fashion using a customized neuroradiology reporting form. STATISTICAL TESTS: Matching parametric statistics represented the number of participants whose brain parameters improved or deteriorated over time. Odds ratio (OR) and 95% confidence intervals (CI) were computed using log regression modeling to determine volume loss, white matter lesions, hemosiderosis, gliosis, cystic changes and enlarged Virchow Robin (VR) spaces. A Kappa (κ) statistic with a 95% CI was calculated to determine rater variability between readers. RESULTS: A significant deterioration was observed in volume loss (OR = 1.083, 95% CI 0.678-1.731, permutation test), white matter changes (OR: 0.754, 95% CI 0.442-1.284, permutation test), and enlargement of VR spaces (OR: 0.775, 95% CI 0.513-1.171). Interrater reliability was low: κ = 0.283, 0.156, and 0.557 for volume loss, white matter changes, and enlargement of VR spaces, respectively. DATA CONCLUSION: There were significant changes in brain volume, white matter lesions, and enlargement of VR spaces. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Associations of preoperative anaemia with healthcare resource use and outcomes after colorectal surgery: a population-based cohort study.

BACKGROUND: Preoperative anaemia is common in patient undergoing colorectal surgery. Understanding the population-level costs of preoperative anaemia will inform development and evaluation of anaemia management at health system levels. METHODS: This was a population-based cohort study using linked, routinely collected data, including residents from Ontario, Canada, aged ≥18 yr who underwent an elective colorectal resection between 2012 and 2022. Primary exposure was preoperative anaemia (haemoglobin <130 g L-1 in males; <120 g L-1 in females). Primary outcome was 30-day costs in 2022 Canadian dollars (CAD), from the perspective of a publicly funded healthcare system. Secondary outcomes included red blood cell transfusion, major adverse events (MAEs), length of stay (LOS), days alive at home (DAH), and readmissions. RESULTS: We included 54,286 patients, with mean 65.3 (range 18-102) years of age and 49.0% females, among which 21 264 (39.2%) had preoperative anaemia. There was an absolute adjusted cost increase of $2671 per person at 30 days after surgery attributable to preoperative anaemia (ratio of means [RoM] 1.05, 95% confidence interval [CI] 1.04-1.06). Compared with the control group, 30-day risks of transfusion (odds ratio [OR] 4.34, 95% CI 4.04-4.66), MAEs (OR 1.14, 95% CI 1.03-1.27), LOS (RoM 1.08, 95% CI 1.07-1.10), and readmissions (OR 1.16, 95% CI 1.08-1.24) were higher in the anaemia group, with reduced DAH (RoM 0.95, 95% CI 0.95-0.96). CONCLUSIONS: Approximately $2671 CAD per person in 30-day health system costs are attributable to preoperative anaemia after colorectal surgery in Ontario, Canada.

Knowledge, protective behaviours, and perception of Lyme disease in an area of emerging risk: results from a cross-sectional survey of adults in Ottawa, Ontario.

BACKGROUND: The number of Lyme disease risk areas in Canada is growing. In regions with emerging tick populations, it is important to emphasize peridomestic risk and the importance of protective behaviours in local public health communication. This study aims to identify characteristics associated with high levels of Lyme disease knowledge and adoption of protective behaviours among residents in the Ottawa, Ontario region. METHODS: A geographically stratified web survey was conducted in November 2020 (n = 2018) to determine knowledge, attitudes, and practices regarding Lyme disease among adult residents. Responses were used to calculate: (i) composite scores for knowledge and adoption of protective practices; and (ii) an exposure risk index based on reported activity in woodlands during the spring-to-fall tick exposure risk period. RESULTS: 60% of respondents had a high knowledge of Lyme disease, yet only 14% indicated they often use five or more measures to protect themselves. Factors strongly associated with a high level of Lyme disease knowledge included being 55 or older (Odds Ratio (OR) = 2.04), living on a property with a yard (OR = 3.22), having a high exposure index (OR = 1.59), and knowing someone previously infected with Lyme disease (OR = 2.05). Strong associations with the adoption of a high number of protective behaviours were observed with membership in a non-Indigenous racialized group (OR = 1.70), living on a property with a yard (OR = 2.37), previous infection with Lyme disease (OR = 2.13), prior tick bite exposure (OR = 1.62), and primarily occupational activity in wooded areas (OR = 2.31). CONCLUSIONS: This study highlights the dynamics between Lyme disease knowledge, patterns of exposure risk awareness, and vigilance of personal protection in a Canadian region with emerging Lyme disease risk. Notably, this study identified gaps between perceived local risk and protective behaviours, presenting opportunities for targeted enhanced communication efforts in areas of Lyme disease emergence.

Population Survival Kinetics Derived from Clinical Trials of Potentially Curable Lung Cancers.

Using digitized data from progression-free survival (PFS) and overall survival Kaplan-Meier curves, one can assess population survival kinetics through exponential decay nonlinear regression analyses. To demonstrate their utility, we analyzed PFS curves from published curative-intent trials of non-small cell lung cancer (NSCLC) adjuvant chemotherapy, adjuvant osimertinib in resected EGFR-mutant NSCLC (ADAURA trial), chemoradiotherapy for inoperable NSCLC, and limited small cell lung cancer (SCLC). These analyses permit assessment of log-linear curve shape and estimation of the proportion of patients cured, PFS half-lives for subpopulations destined to eventually relapse, and probability of eventual relapse in patients remaining progression-free at different time points. The proportion of patients potentially cured was 41% for adjuvant controls, 58% with adjuvant chemotherapy, 17% for ADAURA controls, not assessable with adjuvant osimertinib, 15% with chemoradiotherapy, and 12% for SCLC. Median PFS half-life for relapsing subpopulations was 11.9 months for adjuvant controls, 17.4 months with adjuvant chemotherapy, 24.4 months for ADAURA controls, not assessable with osimertinib, 9.3 months with chemoradiotherapy, and 10.7 months for SCLC. For those remaining relapse-free at 2 and 5 years, the cure probability was 74%/96% for adjuvant controls, 77%/93% with adjuvant chemotherapy, 51%/94% with chemoradiation, and 39%/87% with limited SCLC. Relatively easy population kinetic analyses add useful information.

Prediction Models for Forecasting Risk of Development of Surgical Site Infection after Lower Limb Revascularization Surgery: A Systematic Review.

BACKGROUND: Surgical site infections (SSIs) are a common and potentially preventable complication of lower limb revascularization surgery associated with increased healthcare resource utilization and patient morbidity. We conducted a systematic review to evaluate multivariable prediction models designed to forecast risk of SSI development after these procedures. METHODS: After protocol registration (CRD42022331292), we searched MEDLINE, EMBASE, CENTRAL, and Evidence-Based Medicine Reviews (inception to April 4th, 2023) for studies describing multivariable prediction models designed to forecast risk of SSI in adults after lower limb revascularization surgery. Two investigators independently screened abstracts and full-text articles, extracted data, and assessed risk of bias. A narrative synthesis was performed to summarize predictors included in the models and their calibration and discrimination, validation status, and clinical applicability. RESULTS: Among the 6,671 citations identified, we included 5 studies (n = 23,063 patients). The included studies described 5 unique multivariable prediction models generated through forward selection, backward selection, or Akaike Information Criterion-based methods. Two models were designed to predict any SSI and 3 Szyilagyi grade II (extending into subcutaneous tissue) SSI. Across the 5 models, 18 adjusted predictors (10 of which were preoperative, 3 intraoperative, and 5 postoperative) significantly predicted any SSI and 14 adjusted predictors significantly predict Szilagyi grade II SSI. Female sex, obesity, and chronic obstructive pulmonary disease significantly predicted SSI in more than one model. All models had a "good fit" according to the Hosmer-Lemeshow test (P > 0.05). Model discrimination was quantified using the area under the curve, which ranged from 0.66 to 0.75 across models. Two models were internally validated using non-exhaustive twofold cross-validation and bootstrap resampling. No model was externally validated. Three studies had a high overall risk of bias according to the Prediction model Risk Of Bias ASsessment Tool (PROBAST). CONCLUSIONS: Five multivariable prediction models with moderate discrimination have been developed to forecast risk of SSI development after lower limb revascularization surgery. Given the frequency and consequences of SSI after these procedures, development and external validation of novel prediction models and comparison of these models to the existing models evaluated in this systematic review is warranted.

Edge-to-edge with partial band mitral valve repair compared to replacement and undersized restrictive annuloplasty for ischemic mitral regurgitation.

Objective: Evidence supports replacement over repair for ischemic mitral regurgitation due to improved durability; however, the latter often involves an undersized ring annuloplasty that does not include edge-to-edge approximation. The objective of this study was to evaluate the outcomes of replacement, edge-to-edge leaflet approximation with mild-undersized annuloplasty and undersized ring annuloplasty for ischemic mitral regurgitation. Methods: This is a single-center retrospective study of patients undergoing mitral surgery for moderate-severe or greater ischemic mitral regurgitation, between 2004 and 2020, with mild-undersized annuloplasty, mitral valve replacement, or undersized restrictive annuloplasty (undersized ring annuloplasty). The primary outcome was all-cause mortality. Secondary outcomes included first recurrence of mitral regurgitation, heart failure hospitalization, and composite of valve-related events (bleeding, thromboembolism, endocarditis, and mitral valve reoperation). Results: There were 121, 93, and 78 patients in the mitral valve replacement, mild-undersized annuloplasty, and undersized restrictive annuloplasty groups, respectively, with a median follow-up of 3.1, 5.9, and 3.8 years, respectively. Both mitral valve replacement (hazard ratio, 1.87; 95% CI, 1.029-3.415) and undersized restrictive annuloplasty (hazard ratio, 2.73; 95% CI, 1.480-5.061) were associated with worse survival compared with mild-undersized annuloplasty. At 2 years, the rate of mild-moderate mitral regurgitation was greater in the mild-undersized annuloplasty group compared with the mitral valve replacement group (P = .001) but less than in the undersized restrictive annuloplasty group (P = .001). The rate of recurrent moderate or greater mitral regurgitation at 2 years was similar between mild-undersized annuloplasty and mitral valve replacement groups but significantly higher after undersized restrictive annuloplasty (P < .0001). Mitral valve replacement and undersized restrictive annuloplasty were associated with a significant increase in the incidence of first heart failure hospitalization compared with mild-undersized annuloplasty (P < .001 and P = .001, respectively). Mitral valve replacement was associated with an increased incidence of valve-related events compared with mild-undersized annuloplasty (P = .002). Conclusions: Surgical edge-to-edge approximation in addition to a mild-undersizing annuloplasty offers similar durability compared with replacement, with a lower rate of hospitalization for heart failure, and may confer a survival advantage.

Synthetic data in cancer and cerebrovascular disease research: A novel approach to big data.

OBJECTIVES: Synthetic datasets are artificially manufactured based on real health systems data but do not contain real patient information. We sought to validate the use of synthetic data in stroke and cancer research by conducting a comparison study of cancer patients with ischemic stroke to non-cancer patients with ischemic stroke. DESIGN: retrospective cohort study. SETTING: We used synthetic data generated by MDClone and compared it to its original source data (i.e. real patient data from the Ottawa Hospital Data Warehouse). OUTCOME MEASURES: We compared key differences in demographics, treatment characteristics, length of stay, and costs between cancer patients with ischemic stroke and non-cancer patients with ischemic stroke. We used a binary, multivariable logistic regression model to identify risk factors for recurrent stroke in the cancer population. RESULTS: Using synthetic data, we found cancer patients with ischemic stroke had a lower prevalence of hypertension (52.0% in the cancer cohort vs 57.7% in the non-cancer cohort, p<0.0001), and a higher prevalence of chronic obstructive pulmonary disease (COPD: 8.5% vs 4.7%, p<0.0001), prior ischemic stroke (1.7% vs 0.1%, p<0.001), and prior venous thromboembolism (VTE: 8.2% vs 1.5%, p<0.0001). They also had a longer length of stay (8 days [IQR 3-16] vs 6 days [IQR 3-13], p = 0.011), and higher costs associated with their stroke encounters: $11,498 (IQR $4,440 -$20,668) in the cancer cohort vs $8,084 (IQR $3,947 -$16,706) in the non-cancer cohort (p = 0.0061). A multivariable logistic regression model identified 5 predictors for recurrent ischemic stroke in the cancer cohort using synthetic data; 3 of the same predictors identified using real patient data with similar effect measures. Summary statistics between synthetic and original datasets did not significantly differ, other than slight differences in the distributions of frequencies for numeric data. CONCLUSION: We demonstrated the utility of synthetic data in stroke and cancer research and provided key differences between cancer and non-cancer patients with ischemic stroke. Synthetic data is a powerful tool that can allow researchers to easily explore hypothesis generation, enable data sharing without privacy breaches, and ensure broad access to big data in a rapid, safe, and reliable fashion.

Randomized trial of routine versus on-demand intraoperative extracorporeal membrane oxygenation in lung transplantation: A feasibility study.

In most centers, extracorporeal membrane oxygenation (ECMO) is the preferred means to provide cardiopulmonary support during lung transplantation. However, there is controversy about whether intraoperative venoarterial (VA) ECMO should be used routinely or selectively. A randomized controlled trial is the best way to address this controversy. In this publication, we describe a feasibility study to assess the practicality of a protocol comparing routine versus selective VA-ECMO during lung transplantation. This prospective, single-center, randomized controlled trial screened all patients undergoing lung transplantation. Exclusion criteria include retransplantation, multiorgan transplantation, and cases where ECMO is mandatory. We determined that the trial would be feasible if we could recruit 19 participants over 6 months with less than 10% protocol violations. Based on the completed feasibility study, we conclude that the protocol is feasible and safe, giving us the impetus to pursue a multicenter trial with little risk of failure due to low recruitment.

A randomized trial evaluating the utility of non-targeted biopsies for colorectal neoplasia detection in adults with inflammatory bowel disease: a pilot study protocol.

BACKGROUND: Persons with inflammatory bowel diseases are at increased risk of developing colorectal cancer and require frequent colonoscopy surveillance. Guidelines recommend taking 30 to 40 non-targeted biopsies throughout the colorectum to detect "invisible" neoplasia in this setting, despite a lack of evidence supporting this practice. We sought to assess the utility of this practice through a randomized controlled trial. We first propose an internal pilot study to assess recruitment potential, protocol adherence and data capture to guide the full trial. METHODS: We have designed a multi-centre, parallel-group, non-inferiority randomized controlled trial to test the utility of non-targeted biopsies as an adjunct to colonoscopy surveillance for neoplasia detection in persons with inflammatory bowel disease involving the colorectum in routine clinical practice. Participants are randomized 1:1, stratified by study site, to either standard of care high-definition white-light colonoscopy with 32 to 40 non-targeted biopsies of non-neoplastic-appearing mucosa along with a sampling of abnormal-appearing mucosa (control group) or modified colonoscopy with targeted sampling alone (intervention group). The primary outcome for the full trial will be the proportion of persons with ≥ 1 neoplastic focus detected during colonoscopy. For the pilot phase, we will assess the feasibility of recruiting a minimum of 15% of the estimated sample size within 1 year, under identical conditions as the full trial, while maintaining ≥ 90-95% rate of protocol adherence and data capture. These participants will contribute data to the full trial. The trial is being conducted at 12 centres across Canada, with a total sample size of 1952 persons. DISCUSSIONS: The trial protocol has been approved by the ethics committees of all participating sites, and the pilot study has received funding through the Canadian Institutes of Health Research (PJT 159607). If feasibility metrics are met during the pilot phase, we will complete the full trial. The trial outcomes will contribute to update the practice guidelines in this area. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04067778.

Subclinical Primary Aldosteronism and Cardiovascular Health: A Population-Based Cohort Study.

BACKGROUND: Primary aldosteronism, characterized by overt renin-independent aldosterone production, is a common but underrecognized form of hypertension and cardiovascular disease. Growing evidence suggests that milder and subclinical forms of primary aldosteronism are highly prevalent, yet their contribution to cardiovascular disease is not well characterized. METHODS: This prospective study included 1284 participants between the ages of 40 and 69 years from the randomly sampled population-based CARTaGENE cohort (Québec, Canada). Regression models were used to analyze associations of aldosterone, renin, and the aldosterone-to-renin ratio with the following measures of cardiovascular health: arterial stiffness, assessed by central blood pressure (BP) and pulse wave velocity; adverse cardiac remodeling, captured by cardiac magnetic resonance imaging, including indexed maximum left atrial volume, left ventricular mass index, left ventricular remodeling index, and left ventricular hypertrophy; and incident hypertension. RESULTS: The mean (SD) age of participants was 54 (8) years and 51% were men. The mean (SD) systolic and diastolic BP were 123 (15) and 72 (10) mm Hg, respectively. At baseline, 736 participants (57%) had normal BP and 548 (43%) had hypertension. Higher aldosterone-to-renin ratio, indicative of renin-independent aldosteronism (ie, subclinical primary aldosteronism), was associated with increased arterial stiffness, including increased central BP and pulse wave velocity, along with adverse cardiac remodeling, including increased indexed maximum left atrial volume, left ventricular mass index, and left ventricular remodeling index (all P<0.05). Higher aldosterone-to-renin ratio was also associated with higher odds of left ventricular hypertrophy (odds ratio, 1.32 [95% CI, 1.002-1.73]) and higher odds of developing incident hypertension (odds ratio, 1.29 [95% CI, 1.03-1.62]). All the associations were consistent when assessing participants with normal BP in isolation and were independent of brachial BP. CONCLUSIONS: Independent of brachial BP, a biochemical phenotype of subclinical primary aldosteronism is negatively associated with cardiovascular health, including greater arterial stiffness, adverse cardiac remodeling, and incident hypertension.

Development of an MRI-Based Prediction Model for Anti-TNF Treatment Failure in Perianal Crohn's Disease: A Multicenter Study.

BACKGROUND & AIMS: Clinical and radiologic variables associated with perianal fistula (PAF) outcomes are poorly understood. We developed prediction models for anti-tumor necrosis factor (TNF) treatment failure in patients with Crohn's disease-related PAF. METHODS: In a multicenter retrospective study between 2005 and 2022 we included biologic-naive adults (>17 years) who initiated their first anti-TNF therapy for PAF after pelvic magnetic resonance imaging (MRI). Pretreatment MRI studies were prospectively reread centrally by blinded radiologists. We developed and internally validated a prediction model based on clinical and radiologic parameters to predict the likelihood of anti-TNF treatment failure, clinically, at 6 months. We compared our model and a simplified version of MRI parameters alone with existing imaging-based PAF activity indices (MAGNIFI-CD and modified Van Assche MRI scores) by De Long statistical test. RESULTS: We included 221 patients: 32 ± 14 years, 60% males, 76% complex fistulas; 68% treated with infliximab and 32% treated with adalimumab. Treatment failure occurred in 102 (46%) patients. Our prediction model included age at PAF diagnosis, time to initiate anti-TNF treatment, and smoking and 8 MRI characteristics (supra/extrasphincteric anatomy, fistula length >4.3 cm, primary tracts >1, secondary tracts >1, external openings >1, tract hyperintensity on T1-weighted imaging, horseshoe anatomy, and collections >1.3 cm). Our full and simplified MRI models had fair discriminatory capacity for anti-TNF treatment failure (concordance statistic, 0.67 and 0.65, respectively) and outperformed MAGNIFI-CD (P = .002 and < .0005) and modified Van Assche MRI scores (P < .0001 and < .0001), respectively. CONCLUSIONS: Our risk prediction models consisting of clinical and/or radiologic variables accurately predict treatment failure in patients with PAF.

Point-of-care haemoglobin accuracy and transfusion outcomes in non-cardiac surgery at a Canadian tertiary academic hospital: protocol for the PREMISE observational study.

INTRODUCTION: Transfusions in surgery can be life-saving interventions, but inappropriate transfusions may lack clinical benefit and cause harm. Transfusion decision-making in surgery is complex and frequently informed by haemoglobin (Hgb) measurement in the operating room. Point-of-care testing for haemoglobin (POCT-Hgb) is increasingly relied on given its simplicity and rapid provision of results. POCT-Hgb devices lack adequate validation in the operative setting, particularly for Hgb values within the transfusion zone (60-100 g/L). This study aims to examine the accuracy of intraoperative POCT-Hgb instruments in non-cardiac surgery, and the association between POCT-Hgb measurements and transfusion decision-making. METHODS AND ANALYSIS: PREMISE is an observational prospective method comparison study. Enrolment will occur when adult patients undergoing major non-cardiac surgery require POCT-Hgb, as determined by the treating team. Three concurrent POCT-Hgb results, considered as index tests, will be compared with a laboratory analysis of Hgb (lab-Hgb), considered the gold standard. Participants may have multiple POCT-Hgb measurements during surgery. The primary outcome is the difference in individual Hgb measurements between POCT-Hgb and lab-Hgb, primarily among measurements that are within the transfusion zone. Secondary outcomes include POCT-Hgb accuracy within the entire cohort, postoperative morbidity, mortality and transfusion rates. The sample size is 1750 POCT-Hgb measurements to obtain a minimum of 652 Hgb measurements <100 g/L, based on an estimated incidence of 38%. The sample size was calculated to fit a logistic regression model to predict instances when POCT-Hgb are inaccurate, using 4 g/L as an acceptable margin of error. ETHICS AND DISSEMINATION: Institutional ethics approval has been obtained by the Ottawa Health Science Network-Research Ethics Board prior to initiating the study. Findings from this study will be published in peer-reviewed journals and presented at relevant scientific conferences. Social media will be leveraged to further disseminate the study results and engage with clinicians.

The Association Between Serum Vancomycin Level and Clinical Outcome in Patients With Peritoneal Dialysis Associated Peritonitis.

Introduction: Intraperitoneal (IP) vancomycin is often first-line empiric therapy and then maintenance therapy for peritoneal dialysis (PD) peritonitis. However, how vancomycin serum levels correlate with clinical outcomes remains unclear. Methods: We conducted a retrospective single-center adult cohort study of 98 patients with PD peritonitis treated with IP vancomycin between January 2016 and May 2022. The association between nadir vancomycin level and cure was evaluated in a logistic regression model, first unadjusted and then adjusted for age, sex, weight, glomerular filtration rate (GFR), and total number of days on PD. Vancomycin was assessed both as a continuous exposure (per 1 mg/l increase) and as a categorical exposure (<15 mg/l vs. ≥15 mg/l). A receiver operating characteristic curve (ROC) was created to explore nadir vancomycin level thresholds in an attempt to identify an optimal target level during treatment. Results: Of the patients, 81% achieved cure, and patients with nadir vancomycin level ≥15 mg/l were 7.5 times more likely to experience cure compared to those with a nadir level <15 mg/l (odds ratio [OR] 7.58, 95% confidence interval [CI] 1.71-33.57, P = 0.008). Weight, GFR, days on PD, sex, and age were not independently associated with outcome. The vancomycin level with the greatest discriminatory capacity for cure on the ROC analysis was 14.4 mg/l. Conclusion: Increasing IP vancomycin serum levels are associated with increased odds of cure; and maintaining vancomycin serum levels above 14-15 mg/l throughout the course of PD peritonitis treatment is likely to improve clinical outcomes.

The impact of characters like Tony the Tiger and other child-targeted techniques used in food and beverage marketing.

Introduction: Food marketing's impact is a function of exposure and power, both of which contribute to children's poor diet quality and obesity risk. Children's exposure to food marketing is well documented, however, few studies have assessed the impact of specific persuasive marketing techniques or aspects of 'power' on children. Methods: This study administered an online survey to 1,341 Canadian children (9-12 years) aiming to determine the impact of: (1) child-targeted vs. adult-targeted marketing, and (2) licensed characters vs. spokes characters on children's food preferences and behavioral intentions. Participants were randomized to a single condition in each survey part and viewed 3 static food advertisements displaying the features of that condition (e.g., child-targeted advertising or licensed characters), and answered 3 Likert-scale (5-point) questions after each exposure. For each condition within each research question, there were four outcome variables related to the impact of marketing on children: food preference, purchase intent, pester power, and total impact. ANOVA tested the difference in impact (Likert scores) between conditions overall and for each outcome, with Bonferroni post-hoc tests where necessary. Results: A greater average total impact was observed among children exposed to child-targeted ads (mean Likert score 3.36) vs. adult-targeted ads (mean score 2.75; p < 0.001) or no marketing (mean score 2.81; p < 0.001). Children exposed to ads featuring spokes characters had a higher average total impact (mean score 3.98) vs. licensed characters (mean score 3.80; p < 0.001) and the control (i.e., no characters) (mean score 3.19; p < 0.001), and the total impact of licensed characters was greater than that of no characters. Similar trends were observed for all other outcomes. Discussion: Overall, this study showed that child-targeted ads and those using characters - especially spokes characters - have a strong overall impact on children's food preferences, purchase intents, and pester power, and support the implementation of comprehensive marketing restrictions to protect children.

A Simple Exercise Program for Patients With End-Stage Kidney Disease to Improve Strength and Quality of Life: Clinical Research Protocol.

Background: Most patients with end-stage kidney disease (ESKD) appreciate the importance of exercise and would like to increase their physical activity; however, they report a few key barriers, including (1) lack of physician advice to do so, (2) lack of safe and convenient programs (ie, appropriate for home or neighborhood), and (3) cost. Importantly, patients indicated in a previous survey that they would prefer an exercise program that improves muscle strength and symptoms, and are less interested in cardiovascular disease prevention. Objective: To test the feasibility of a simple, prescribed exercise program using Nordic walking poles in patients with ESKD treated with dialysis. Design: Randomized multicenter pilot trial of an exercise intervention that includes Nordic walking poles, personalized physician exercise prescriptions, pedometers, and access to exercise videos, compared with standard of care, in patients being treated with maintenance dialysis. Setting: Multicenter tertiary care centers in Canada. Patients: Ambulatory adult patients with ESKD treated with peritoneal dialysis or hemodialysis (HD) for at least 6 months at participating sites are potentially eligible. Inclusion criteria include ability to use Nordic walking poles (either de novo or in place of mobility aid) and to provide informed consent in English or in French. Exclusion criteria include (1) any absolute contraindication to exercise, (2) baseline step count >8000 steps/day, (3) planned living donor kidney transplant, and (4) participation in another interventional trial that may affect the results of this study. Methods: This is a randomized multicenter pilot trial of an exercise intervention that consists of a prescription to exercise using Nordic walking poles, a pedometer to track activity, and access to exercise videos, with the comparator of standard of care (dialysis unit staff encouragement to exercise) in patients being treated with maintenance dialysis. Randomization is concealed and uses a 1:1 ratio for group assignment. Our specific aims are to determine the feasibility of patient recruitment, adherence to the exercise program (verified by step counts), and efficacy of the intervention on patient-important outcomes that were assessed as a priority by patients in a prior survey-specifically strength, fatigue, and sleep. We record days spent in hospital and loss of independent living to inform sample size calculations for a definitive trial of exercise in patient with ESKD treated with dialysis. Adverse events are closely monitored. Outcomes: Primary: Our recruitment goal is 90 to 150 patients over 27 months; adherence success will be defined if >75% of randomized patients, excluding those who are transplanted or deceased, achieve >80% of their prescribed steps at 6 and 12 months. Secondary Efficacy Outcomes: (1) strength-hand grip strength and 5 times sit to stand, (2) energy-Short Form (SF)-36 vitality subscale, and (3) sleep-Pittsburg Sleep Quality Index will be assessed at baseline, 6, and 12 months. Results: Trial recruitment started before the COVID-19 pandemic and the pandemic led to many interruptions and delays. Online exercise Web sites and a tailored video were added to the protocol to encourage activity when participants were unable or reluctant to walk in public places. Limitations: This trial was designed to include ambulatory patients with ESKD and does not address the burden of disease in patients with very restricted mobility. Trial Registration: NCT03787589.

Contexte: La plupart des patients atteints d'insuffisance rénale terminale (IRT) comprennent l'importance de l'exercice physique et souhaitent augmenter leur niveau d'activité. Ils signalent toutefois quelques obstacles, notamment 1) le manque de conseils médicaux pour le faire; 2) le manque de programmes sécuritaires et faciles (c.-à-d. pouvant être suivis à la maison ou dans le quartier); et 3) les coûts. Il convient de noter que les patients avaient indiqué dans une enquête précédente préférer un programme d'exercices améliorant la force musculaire et les symptômes liés à la maladie, et être moins intéressés par la prévention des maladies cardiovasculaires. Objectif: Dans une population de patients atteints d'IRT traités par dialyse, tester la faisabilité d'un programme prescrit et simple à suivre d'exercices impliquant l'utilisation de bâtons de marche nordique. Conception: Essai pilote randomisé multicentrique mené chez des patients traités par dialyse d'entretien. L'essai compare les soins habituels à une intervention comprenant des exercices avec bâtons de marche nordique, un programme personnalisé prescrit par un médecin, un podomètre et l'accès à des vidéos d'exercices. Cadre: Plusieurs centres de soins tertiaires au Canada. Sujets: Tous les patients adultes ambulatoires atteints d'IRT traités par dialyse péritonéale ou hémodialyse depuis au moins 6 mois dans les sites participants sont potentiellement admissibles. Pour être inclus, les patients doivent pouvoir utiliser des bâtons de marche nordique (de novo ou en remplacement de l'aide à la mobilité) et fournir un consentement éclairé en anglais ou en français. Les critères d'exclusion sont : 1) toute contre-indication absolue à l'exercice; 2) le fait de marcher déjà au moins 8 000 pas/jour; 3) avoir une transplantation rénale d'un donneur vivant prévue; 4) la participation à un autre essai interventionnel susceptible d'affecter les résultats de la présente étude. Méthodologie: Il s'agit d'un essai pilote randomisé multicentrique examinant une intervention en matière d'activité physique. L'intervention consiste en une prescription d'activité physique à l'aide de bâtons de marche nordique, elle donne accès à un podomètre pour suivre l'activité, ainsi qu'à des vidéos d'exercices; le comparateur est la norme de soins (encouragement par le personnel de l'unité de dialyse à pratiquer une activité physique) pour les patients traités par dialyse d'entretien. La randomisation est masquée et utilise un ratio de 1:1 pour l'affectation aux groupes. Nous examinons la faisabilité du recrutement des patients, l'observance du programme d'exercices (vérifiée par le nombre de pas) et l'efficacité de l'intervention sur les résultats de santé ayant été jugés comme importants et prioritaires par les patients dans une enquête précédente ­ plus précisément la force, la fatigue et le sommeil. Nous enregistrons le nombre de jours passés à l'hôpital et la perte de vie autonome afin d'éclairer les calculs de la taille de l'échantillon d'un essai définitif qui portera sur l'activité physique en contexte d'HD. Les événements indésirables sont étroitement surveillés. Mesures: Primaires : nous souhaitons recruter 90 à 150 patients sur une période de 27 mois; l'observance sera jugée comme un succès si plus de 75 % des patients randomisés (excluant les patients transplantés ou décédés) atteignent plus de 80 % de leur prescription de nombres de pas/jour après 6 et 12 mois. Paramètres secondaires d'efficacité : 1) Force ­ mesure de la force de préhension et 5 fois l'exercice de se lever d'une position assise; 2) Énergie ­ sous-échelle du test de vitalité SF-36; et 3) Sommeil ­ mesure de l'Indice de la qualité du sommeil Pittsburg à l'inclusion et après 6 mois et 12 mois. Résultats: Le recrutement s'est amorcé avant la pandémie de COVID-19, puis celle-ci a entraîné de nombreuses interruptions et retards. Des sites d'exercices en ligne et une vidéo personnalisée ont été ajoutés au protocole afin d'encourager les patients à continuer de faire de l'activité physique lorsqu'ils ne pouvaient pas marcher dans des lieux publics ou étaient réticents à le faire. Limites: Cet essai a été conçu pour inclure des patients ambulatoires atteints d'IRT, il ne traite pas du fardeau de la maladie chez les patients à mobilité très restreinte.

Dietary supplements to reduce symptom severity and duration in people with SARS-CoV-2: a double-blind randomised controlled trial.

BACKGROUND: COVID-19 has caused morbidity, hospitalisation and mortality worldwide. Despite effective vaccines, there is still a need for effective treatments, especially for people in the community. Dietary supplements have long been used to treat respiratory infections, and preliminary evidence indicates some may be effective in people with COVID-19. We sought to evaluate whether a combination of vitamin C, vitamin D3, vitamin K2 and zinc could improve overall health and decrease symptom burden in outpatients diagnosed with COVID-19. METHODS: Participants were randomised to receive either vitamin C (6 g), vitamin D3 (1000 units), vitamin K2 (240 µg) and zinc acetate (75 mg) or placebo daily for 21 days and were followed for 12 weeks. An additional loading dose of 50 000 units vitamin D3 (or placebo) was given on day one. The primary outcome was participant-reported overall health using the EuroQol Visual Assessment Scale summed over 21 days. Secondary outcomes included health status, symptom severity, symptom duration, delayed return to usual health, frequency of hospitalisation and mortality. RESULTS: 90 patients (46 control, 44 treatment) were randomised. The study was stopped prematurely due to insufficient capacity for recruitment. The mean difference (control-treatment) in cumulative overall health was -37.4 (95% CI -157.2 to 82.3), p=0.53 on a scale of 0-2100. No clinically or statistically significant differences were seen in any secondary outcomes. INTERPRETATION: In this double-blind, placebo-controlled, randomised trial of outpatients diagnosed with COVID-19, the dietary supplements vitamin C, vitamin D3, vitamin K2 and zinc acetate showed no clinically or statistically significant effects on the documented measures of health compared with a placebo when given for 21 days. Termination due to feasibility limited our ability to demonstrate the efficacy of these supplements for COVID-19. Further research is needed to determine clinical utility. TRIAL REGISTRATION NUMBER: NCT04780061.

Resource allocation decisions under pandemic conditions: A cross-sectional survey of Ontario physicians.

The COVID-19 pandemic has forced physicians to confront difficult choices regarding the allocation of scarce resources, such as ventilators and critical care beds. Developing policies to guide the allocation of such resources has proven challenging. An understanding of physicians' attitudes and beliefs surrounding resource allocation could help inform policymaking. As a replication and extension of a survey of Ottawa physicians conducted in 2020, we surveyed physicians across Ontario, Canada in April 2021. This survey examined physicians' sense of preparedness to allocate critical care resources during the pandemic, attitudes concerning resource allocation policy, and approaches to resource allocation decision-making. Of the 253 responses included for analysis, the majority (67%) of respondents indicated feeling "somewhat" or "a little prepared" to make resource allocation decisions, while 20% indicated feeling "not at all prepared." Most respondents (86%) agreed that a policy to guide resource allocation in the event of scarcity should exist. Physicians overwhelmingly agreed that important factors to consider when making resource allocation decisions included the patient likelihood of survival, frailty index, comorbidities, and cognitive status. Responses from the province-wide survey conducted in 2021 resemble the results of an analogous survey of Ottawa physicians conducted in 2020. Physicians generally felt underprepared to make resource allocation decisions and agreed that official policies should guide such decisions. Identification of factors relevant to resource allocation was remarkably consistent across this sample and that taken in 2020.

Impaired Renal Function and Major Cardiovascular Events in Young Adults.

BACKGROUND: Cardiovascular (CV) disease in young adults (aged 18-39 years) is on the rise. Whether subclinical reductions in kidney function (ie, estimated glomerular filtration rate [eGFR] above the current threshold for chronic kidney disease but below age-expected values) are associated with elevated CV risk is unknown. OBJECTIVES: The goal of this study was to examine age-specific associations of subclinical eGFR reductions in young adults with major adverse cardiovascular events (MACEs) and MACE plus heart failure (MACE+). METHODS: A retrospective cohort study of 8.7 million individuals (3.6 million aged 18-39 years) was constructed using linked provincial health care data sets from Ontario, Canada (January 2008-March 2021). Cox models were used to examine the association of categorized eGFR (50-120 mL/min/1.73 m2) with MACE (first of CV mortality, acute coronary syndrome, and ischemic stroke) and MACE+, stratified according to age (18-39, 40-49, and 50-65 years). RESULTS: In the study cohort (mean age 41.3 years; mean eGFR 104.2 mL/min/1.73 m2; median follow-up 9.2 years), a stepwise increase in the relative risk of MACE and MACE+ was observed as early as eGFR <80 mL/min/1.73 m2 in young adults (eg, for MACE, at eGFR 70-79 mL/min/1.73 m2, ages 18-30 years: 2.37 events per 1,000 person years [HR: 1.31; 95% CI: 1.27-1.40]; ages 40-49 years: 6.26 events per 1,000 person years [HR: 1.09; 95% CI: 1.06-1.12]; ages 50-65 years: 14.9 events per 1,000 person years [HR: 1.07; 95% CI: 1.05-1.08]). Results persisted for each MACE component and in additional analyses (stratifying according to past CV disease, accounting for albuminuria at index, and using repeated eGFR measures). CONCLUSIONS: In young adults, eGFR below age-expected values were associated with an elevated risk for MACE and MACE+, warranting age-appropriate risk stratification, proactive monitoring, and timely intervention.