Efficacy of cannabinoids compared to the current standard treatments on symptom relief in persons with multiple sclerosis (CANSEP trial): study protocol for a randomized clinical trial.

Background: Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system. More than 90,000 Canadians are affected; a cure is yet to be found. Available treatments to manage the disease course are only partially effective. For many years, persons with MS (PwMS) have used cannabis to relax, to reduce pain and spasticity, or to improve sleep and daily functioning, despite the lack of scientific evidence on the efficacy of specific cannabinoids [i.e., tetrahydrocannabinol (THC) and cannabidiol (CBD)] on these MS symptoms. The purpose of this clinical trial is to assess the effectiveness of different doses of these cannabinoids, alone or combined, on spasticity relief, compared to placebo. Moreover, we aim to determine which treatment is best effective to address other key MS conditions. Methods: A double-blinded, randomized, factorial, placebo-controlled trial will be performed. We intend to include up to 250 PwMS aged over 21 recruited from the Centre hospitalier de l'Université de Montréal MS Clinic. PwMS will be randomly assigned on a 1:1:1:1 ratio to one of the trial arms: THC alone, CBD alone, THC/CBD combination, or placebo, using stratified blocked randomization, with random blocks within each stratum. The primary outcome is a self-assessment of spasticity using the mean Numeric Rating Scale score over 7 days. The main outcome will be the difference in this score at 4 weeks compared to baseline. Secondary outcomes include assessments of spasticity as measured by a clinician, pain, fatigue, sleep, bowel, bladder, and sexual dysfunction, restless legs syndrome, mental health, quality of life, mobility, cognitive functioning, and adverse events. Treatment responders are eligible for a 12-week extension phase, using the same treatment allocation and assessments. Discussion: Previous clinical studies examined the efficacy of cannabis-based medicines in PwMS, mostly using products with 1:1 THC/CBD ratio. The major barrier to effectively use cannabis in real-world clinical settings is the lack of evidence on benefits of specific cannabinoids and information on possible related risks. The CANSEP study will contribute to overcome these limitations and identify the risks and benefits of cannabis-based treatments in PwMS. Clinical trial registration: ClinicalTrials.Gov, NCT05092191.

Inter-visit and inter-reader reproducibility of multi-parametric diffusion-weighted MR imaging in longitudinally imaged patients with metabolic dysfunction-associated fatty liver disease and healthy volunteers.

BACKGROUND: Despite the widespread use of diffusion-weighted imaging (DWI) in metabolic dysfunction-associated fatty liver disease (MAFLD), MRI acquisition and quantification techniques vary in the literature suggesting the need for established and reproducible protocols. The goal of this study was to assess inter-visit and inter-reader reproducibility of DWI- and IVIM-derived parameters in patients with MAFLD and healthy volunteers using extensive sampling of the "fast" compartment, non-rigid registration, and exclusion voxels with poor fit quality. METHODS: From June 2019 to April 2023, 31 subjects (20 patients with biopsy-proven MAFLD and 11 healthy volunteers) were included in this IRB-approved study. Subjects underwent MRI examinations twice within 40 days. 3.0 T DWI was acquired using a respiratory-triggered spin-echo diffusion-weighted echo-planar imaging sequence (b-values of 0, 10, 20, 30, 40, 50, 100, 200, 400, 800 s/mm2). DWI series were co-registered prior to voxel-wise non-linear regression of the IVIM model and voxels with poor fit quality were excluded (normalized root mean squared error ≥ 0.05). IVIM parameters (perfusion fraction, f; diffusion coefficient, D; and pseudo-diffusion coefficient, D*), and apparent diffusion coefficients (ADC) were computed from manual segmentation of the right liver lobe performed by two analysts on two MRI examinations. RESULTS: All results are reported for f, D, D*, and ADC respectively. For inter-reader agreement on the first visit, ICC were of 0.985, 0.994, 0.986, and 0.993 respectively. For intra-reader agreement of analyst 1 assessed on both imaging examinations, ICC between visits were of 0.805, 0.759, 0.511, and 0.850 respectively. For inter-reader agreement on the first visit, mean bias and 95 % limits of agreement were (0.00 ± 0.03), (-0.01 ± 0.03) × 10-3 mm2/s, (0.70 ± 10.40) × 10-3 mm2/s, and (-0.02 ± 0.04) × 10-3 mm2/s respectively. For intra-reader agreement of analyst 1, mean bias and 95 % limits of agreement were (0.01 ± 0.09) × 10-3 mm2/s, (-0.01 ± 0.21) × 10-3 mm2/s, (-13.37 ± 56.19) × 10-3 mm2/s, and (-0.01 ± 0.16) × 10-3 mm2/s respectively. Except for parameter D* that was associated with between-subjects parameter variability (P = 0.009), there was no significant variability between subjects, examinations, or readers. CONCLUSION: With our approach, IVIM parameters f, D, D*, and ADC provided excellent inter-reader agreement and good to very good inter-visit or intra-reader agreement, thus showing the reproducibility of IVIM-DWI of the liver in MAFLD patients and volunteers.

Role of Physical Activity and Sedentary Behaviors on Vascular and Myocardial Structure and Function in Type 1 Diabetes.

OBJECTIVE: To estimate associations between physical activity and sedentary behaviors and early markers of cardiovascular diseases in adolescents with and without type 1 diabetes. STUDY DESIGN: Cross-sectional data stem from the CARdiovascular Disease risk in pEdiatric type 1 diAbetes (CARDEA) study, a study investigating early cardiovascular disease development in 100 adolescents with type 1 diabetes recruited at Sainte-Justine University Hospital Diabetes Clinic and 97 healthy adolescents without diabetes (14-18 years), in Montreal, Canada. Outcomes included arterial stiffness by pulse-wave velocity, endothelial function (velocity time integral) by flow-mediated dilation test, and cardiac magnetic resonance imaging markers. Moderate-to-vigorous physical activity (MVPA) and sedentary time were estimated by accelerometry and leisure screen time by questionnaire. We estimated multivariable linear regression models stratified by group. RESULTS: In adolescents with type 1 diabetes, 10-minutes daily increase in MVPA was associated with 3.69 g/m (95% CI: -1.16; 8.54) higher left ventricular (LV) mass/height and 1-hour increase in device-measured sedentary time with 0.68 mm (0.20; 1.16) higher wall thickness but only in those with glycated hemoglobin ≤7.5%. In healthy adolescents, a 10-minute increase in MVPA was associated with 1.32 g/m (-0.03; 2.66) higher LV mass/height. Every 1-hour increase in sedentary time was associated with -1.82 cm (-3.25; -0.39) lower velocity time integral, -2.99 g/m (-5.03; -0.95) lower LV mass/height, and -0.47 mm (-0.82; -0.12) lower wall thickness. CONCLUSIONS: Being active and limiting sedentary time appears beneficial for cardiac structure and endothelial function in healthy adolescents; however, adequate glycemic control combined with higher levels of MVPA may be required for adolescents with type 1 diabetes to overcome the impact of diabetes.

Prospective associations between neighborhood features and body mass index in Montreal adolescents.

PURPOSE: To investigate the association between the neighborhood built environment and trajectories of body mass index (BMI) in youth. METHODS: Data were collected in a prospective study of 1293 adolescents in Montreal. Built environment variables were obtained from public databases for road networks, land use, and the Canadian Census. Anthropometric data were collected when participants were ages 12.5, 15 and 17 years. We undertook hierarchical cluster analysis to identify contrasting neighborhood types based on features of the built environment (e.g., vegetation, population density, walkability). Associations between neighborhood type and trajectories of BMI z-score (BMIz) were estimated using multivariable linear mixed regression analyses, stratified by sex. RESULTS: We identified three neighborhood types: Urban, Suburban, and Village. In contrast to the Urban type, the Suburban type was characterized by more vegetation, few services and low population density. Village and Suburban types were similar, but the former had greater land use diversity, population density with more parks and a denser food environment. Among girls, living in Urban types was associated with decreasing BMIz trajectories. Living in Village types was associated with increasing BMIz trajectories. No associations were observed among boys. CONCLUSIONS: Neighborhoods characterized by greater opportunities for active living appear to be less obesogenic, particularly among girls.

Characterizing Trends in the Use of Food Donations and Other Food-Related Community-Based Social Assistance Programs in a Cohort of New Food Bank Users in Quebec, Canada.

Objective: To characterize 12-month trends in the use of food donations and other food-related community-based social assistance programs (CB-SAPs) during the first year following the enrollment of new food bank (FB) users in Quebec, Canada. Methods: A cohort of 1,001 newly registered FB-users in Quebec from the Pathways Study were followed-up during 12-month following baseline assessment. Outcomes were monthly use of food donations and other food-related CB-SAPs. Main predictors were alternative food source utilization (AFSU) profiles: 1) exclusive-FB-users; 2) FB+fruit/vegetable-market-users; and 3) Multiple/diverse-AFS-users. Covariates included sociodemographic characteristics, health status, and major life events. We fit Bayesian hierarchical mixed-effect models, accounting for spatial clustering, temporal correlation, and censoring. Results: We observed an overall downward trend of food donation use among study completers (n = 745). Each AFSU profile had a distinctive monthly trend of food donation use, but probabilities of use across the three profiles overlapped, between 44% and 55%. The use of other food-related CB-SAPs was low and not correlated with AFSU profiles. Conclusion: De novo FB-users use food donations in different ways over time according to specific contextual AFSU profiles.

Comparison of three frailty measures for predicting hospitalization and mortality in the Canadian Longitudinal Study on Aging.

BACKGROUND: Few studies have compared different measures of frailty for predicting adverse outcomes. It remains unknown which frailty measurement approach best predicts healthcare utilization such as hospitalization and mortality. AIMS: This study aims to compare three approaches to measuring frailty-grip strength, frailty phenotype, and frailty index-in predicting hospitalization and mortality among middle-aged and older Canadians. METHODS: We analyzed baseline and the first 3-year follow-up data for 30,097 participants aged 45 to 85 years from the comprehensive cohort of the Canadian Longitudinal Study on Aging (CLSA). Using separate logistic regression models adjusted for multimorbidity, age and biological sex, we predicted participants' risks for overnight hospitalization in the past 12 months and mortality, at the first 3-year follow-up, using each of the three frailty measurements at baseline. Model discrimination was assessed using Harrell's c-statistic and calibration assessed using calibration plots. RESULTS: The predictive performance of all three measures of frailty were roughly similar when predicting overnight hospitalization and mortality risk among CLSA participants. Model discrimination measured using c-statistics ranged from 0.67 to 0.69 for hospitalization and 0.79 to 0.80 for mortality. All measures of frailty yielded strong model calibration. DISCUSSION AND CONCLUSION: All three measures of frailty had similar predictive performance. Discrimination was modest for predicting hospitalization and superior in predicting mortality. This likely reflects the objective nature of mortality as an outcome and the challenges in reducing the complex concept of healthcare utilization to a single variable such as any overnight hospitalization.

Investigating social inequalities in children's independent mobility, active transportation and outdoor free play in two Canadian cities.

Background: Active transportation (AT) and free play (FP) are the primary ways in which children engage in unstructured physical activity in cities, with independent mobility (IM) gaining increased attention as a potential precursor of AT and FP. However, current trends show that children are engaging in less FP and AT, and have less IM, than previous generations and it is not well understood how these practices, and their interrelatedness, differ by neighbourhood-level socio-economic stats (SES) and municipal contexts. Objectives: This study aims to address the gaps in knowledge by quantifying, comparing, and correlating IM, AT, and FP practices in high and low-SES neighbourhoods within and across the cities of Montreal and Kingston, Canada. Methods: 584 questionnaires were distributed among children in grades 1 to 5, living in low- and high-SES neighbourhoods of these two citiesResultsEngagement in the three practices was low in every study neighbourhood, though all three practices were higher in high-SES compared to low-SES neighbourhoods in both cities. Levels of FP were higher in Kingston compared to Montreal, while AT was higher in Montreal than in Kingston. Conclusion: This study revealed social inequalities in all three of these practices based on socioeconomic status and city. Since IM is likely a precursor to both independent FP and AT, more research is warranted into how our cities can become more conducive to IM in children, particularly in low SES neighbourhoods where children have less freedom of movement independently and otherwise.

Associations Between Weight-Loss Attempts, Weight-Related Stress, and Body Image During Childhood and Adolescence in Children With Parental Obesity.

Background: Few longitudinal studies have investigated the role of weight-loss attempts or weight-related stress on body image during childhood. We examined whether weight-loss attempts and weight-related stress are associated with weight misperception and body dissatisfaction across childhood and adolescence. Methods: Data were drawn from the Quebec Adipose and Lifestyle InvesTigation in Youth (QUALITY) cohort of Canadian children with parental obesity (8-10 years: n = 630; 10-12 years: n = 564; 15-17 years: n = 377). We assessed weight-loss attempts and weight-related stress at baseline and first follow-up, and perceived and desired silhouettes at first and second follow-up with questionnaires. Weight misperception consisted of the difference in BMI z-score (zBMI) from the perceived silhouette and the measured zBMI. Body dissatisfaction consisted of the discordance between perceived and desired silhouettes. We estimated multivariable mixed-effects regression models adjusting for age, sex, pubertal stage, parental BMI and education, and sport-based teasing. Results: Weight loss attempts were associated with a higher weight misperception score (ever tried, beta [95% confidence intervals; CI]: 0.13 [0.01-0.24]) and with 2.13 times higher desire to be thinner (95% CI: 1.39-3.26) at the subsequent follow-up. Similarly, children stressed by their weight had a higher misperception score (beta [95% CI]: 0.15 [0.02-0.27]) and greater desire to be thinner at the next follow-up (odds ratio [95% CI]: 1.73 [0.999-3.00]). Conclusions: Weight-loss attempts and weight-related stress in children and adolescents are associated with weight misperception and body dissatisfaction, supporting empowerment and counseling focusing on healthy eating behaviors and a positive body image. Clinical Trial Registration Number: NCT03356262.

Trajectories of opioid consumption as predictors of patient-reported outcomes among individuals attending multidisciplinary pain treatment clinics.

PURPOSE: This study aimed to identify opioid consumption trajectories among persons living with chronic pain (CP) and put them in relation to patient-reported outcomes 6 months after initiating multidisciplinary pain treatment. METHODS: This study used data from the Quebec Pain Registry (2008-2014) linked to longitudinal Quebec health insurance databases. We included adults diagnosed with CP and covered by the Quebec public prescription drug insurance plan. The daily cumulative opioid doses in the first 6 months after initiating multidisciplinary pain treatment were transformed into morphine milligram equivalents. An individual-centered approach involving principal factor and cluster analyses applied to longitudinal statistical indicators of opioid use was conducted to classify trajectories. Multivariate regression models were applied to evaluate the associations between trajectory group membership and outcomes at 6-month follow-up (pain intensity, pain interference, depression, and physical and mental health-related quality of life). RESULTS: We identified three trajectories of opioid consumption: "no or very low and stable" opioid consumption (n = 2067, 96.3%), "increasing" opioid consumption (n = 40, 1.9%), and "decreasing" opioid consumption (n = 39, 1.8%). Patients in the "no or very low and stable" trajectory were less likely to be current smokers, experience polypharmacy, use opioids or benzodiazepine preceding their first visit, or experience pain interference at treatment initiation. Patients in the "increasing" opioid consumption group had significantly greater depression scores at 6-month compared to patients in the "no or very low and stable" trajectory group. CONCLUSION: Opioid consumption trajectories do not seem to be important determinants of most PROs 6 months after initiating multidisciplinary pain treatment.

The association between grip strength and carotid intima media thickness: A Mendelian randomization analysis of the Canadian Longitudinal Study on Aging.

BACKGROUND: Several two-sample Mendelian randomization studies have reported discordant results concerning the association between grip strength and cardiovascular disease, possibly due to the number of instrumental variables used, pleiotropic bias, and/ or effect modification by age and sex. METHODS: We conducted a sex- and age-stratified one-sample Mendelian randomization study in the Canadian Longitudinal Study on Aging. We investigated whether grip strength is associated with carotid intima media thickness (cIMT), a marker of vascular atherosclerosis event risk, using eighteen single nucleotide polymorphisms (SNP) identified as specifically associated with grip strength. RESULTS: A total of 20,258 participants of self-reported European ancestry were included in the analytic sample. Our Mendelian randomization findings suggest a statistically significant association between grip strength and cIMT (MR coefficient of 0.02 (95% CI: 0.01, 0.04)). We found no statistically significant differences between sexes (p-value = 0.201), or age groups [(≤ 60 years old versus >60 years old); p-value = 0.421]. CONCLUSION: This study provides evidence that grip strength is inversely associated with cIMT. Our one-sample MR study design allowed us to demonstrate that there is no evidence of heterogeneity of effects according to age group or biological sex.

The application of target trials with longitudinal targeted maximum likelihood estimation to assess the effect of alcohol consumption in adolescence on depressive symptoms in adulthood.

Time-varying confounding is a common challenge for causal inference in observational studies with time-varying treatments, long follow-up periods, and participant dropout. Confounder adjustment using traditional approaches can be limited by data sparsity, weight instability and computational issues. The Nicotine Dependence in Teens (NDIT) study is a prospective cohort study involving 24 data collection cycles from 1999 to date, among 1,294 students recruited from 10 high schools in Montreal, Canada, including follow-up into adulthood. Our aim is to estimate associations between the timing of alcohol initiation and the cumulative duration of alcohol use on depression symptoms in adulthood. Based on the target trials framework, we define intention-to-treat and as-treated parameters in a marginal structural model with sex as a potential effect-modifier. We then use the observational data to emulate the trials. For estimation, we use pooled longitudinal target maximum likelihood estimation (LTMLE), a plug-in estimator with double robust and local efficiency properties. We describe strategies for dealing with high-dimensional potential drinking patterns and practical positivity violations due to a long follow-up time, including modifying the effect of interest by removing sparsely observed drinking patterns from the loss function and applying longitudinal modified treatment policies to represent the effect of discouraging drinking.

A Brief Digital Screening and Intervention Tool for Parental and Adolescent Tobacco and Electronic Cigarette Use in Pediatric Medical Care in Canada: Protocol for a Pilot Randomized Controlled Trial.

BACKGROUND: Though rates of tobacco smoking have decreased consistently over the past 3 decades, cigarette use remains the top preventable cause of premature death in North America. The Clinical Effort Against Secondhand Smoke Exposure (CEASE) is a medical clinic-based intervention that systematically screens parents for tobacco use and offers them direct access to evidence-based smoking cessation services. While the effectiveness of CEASE for parents who smoke has already been demonstrated in the United States, the CEASE model has not yet been tested in Canada, among parents who use e-cigarettes, or among adolescents who use cigarettes and e-cigarettes. OBJECTIVE: We aim to demonstrate the feasibility and evaluate the preliminary effectiveness of the CEASE program for parental smoking cessation and its adapted version for adolescent smoking cessation and adolescent and parental vaping cessation. METHODS: We will approach parents or guardians of children aged between 0 and 17 years, as well as adolescent patients aged between 14 and 17 years, from a tertiary care pediatric hospital in Montreal, Quebec, Canada, for participation in this single-blinded, pilot randomized controlled trial. Eligible participants are those who report using tobacco cigarettes or e-cigarettes at least once in the last 7 days and present to an outpatient pediatric clinic for a scheduled appointment. Our recruitment target is 100 participants: 50 parents or guardians of children aged 17 years or younger, and 50 adolescents aged between 14 and 17 years. The feasibility of implementation of the CEASE model will be measured by recruitment and retention rates for all 4 participant groups (stratified as follows: parents who use cigarettes, parents who use e-cigarettes exclusively, adolescents who use cigarettes, and adolescents who use e-cigarettes exclusively). Parent and adolescent participants within each group are randomized to the intervention and control groups using a 1:1 ratio through a computer-generated randomization list. Preliminary effectiveness outcomes include self-reported smoking and e-cigarette cessation, use of cessation resources, changes in smoking and e-cigarette use, motivation to quit, and quit attempts among participants. Participants complete electronic questionnaires on a tablet in the clinic at baseline as well as electronic follow-up questionnaires at 1, 3, and 6 months. Individuals reporting successful quit attempts are invited to provide a urine sample for cotinine testing to biochemically confirm quit. Analyses include descriptive statistics as well as exploratory trajectory analyses of smoking, e-cigarette use, and motivation to quit. RESULTS: Research activities began in June 2022. Participant enrollment and data collection began in February 2023 and are expected to be completed in 15 months. CONCLUSIONS: There is a strong need for effective and cost-effective smoking and vaping cessation interventions for parents and adolescents. If successful, this study will help inform the preparation of a fully powered randomized controlled trial of CEASE in Canada in these populations. TRIAL REGISTRATION: Clinicaltrials.gov NCT05366790; https://www.clinicaltrials.gov/study/NCT05366790. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47978.

Longitudinal Associations Between Body-Related Self-Conscious Emotions and Weight Control Status During Adolescence.

PURPOSE: Half of adolescents are trying to change their weight and body-related self-conscious emotions may influence these intentions. We estimated associations between body-related shame, guilt, embarrassment, envy, authentic pride, and hubristic pride and weight control status (trying to maintain, lose, or gain weight) throughout adolescence in girls and boys. METHODS: Six annual cycles of self-administered questionnaires were collected from age 12-17 in the Monitoring Activities of Teenagers to Comprehend their Habits (MATCH) study (n = 776). Average associations over all cycles were estimated with generalized estimating equations to describe the relationship between emotions (predictors) and weight control status (outcome). To explore the impact of changes in emotions on weight control status, fixed effects logistic regressions were used. Separate models were conducted for each emotion and for boys and girls. RESULTS: On average, boys and girls with higher scores for negative emotions (shame, guilt, embarrassment and, exclusively among girls, envy) had higher odds of trying to lose weight. Higher scores for positive emotions (authentic and hubristic pride) were associated with lower odds of trying to lose weight among girls. Higher scores for authentic pride were associated with trying to gain weight among boys. Girls with increases in any of the negative emotions presented higher odds of trying to lose weight. Girls with increases in hubristic pride had increased odds of trying to maintain weight. DISCUSSION: Body-related self-conscious emotions may be promising healthy-weight intervention targets as they represent important predictors of weight control status, particularly in girls.

The Pathways study: a cohort study of new food-aid users in rural, semi urban, and urban areas of Quebec, Canada.

BACKGROUND: While considerable research has been conducted on household food insecurity (HFI), little research has examined the effects of food donation programs on users' living conditions. The Pathways study was established to investigate the long-term effects of food donation programs on food insecurity as well as other critical outcomes, such as diet, health, and social support. Herein, we describe the design of the Pathways Study and the participants' characteristics at baseline. METHODS: The Pathways study is a prospective cohort study of 1001 food-aid users in Quebec (Canada). We recruited newly registered users of food donation programs from 106 community-based food-aid organizations that partnered with the study. Baseline data were collected through face-to-face interviews from September 2018 to January 2020, with planned follow-up interviews at 12 and 24 months after enrollment. Household food insecurity, diet, food competencies, food shopping behaviors, perceived food environment, health status, social support and isolation, sociodemographic characteristics, housing conditions, negative life events, and the impacts of COVID-19 were assessed with validated questionnaires. RESULTS: The cohort included 1001 participants living in rural (n = 181), semi-urban (n = 250), and urban areas (n = 570). Overall, household food insecurity was reported as severe among 46.2% and moderate in 36.9% of participants. Severe household food insecurity was more prevalent in rural (51.4%) and urban (47.8%) areas compared to semi-urban (39%) areas. Overall, 76.1% of participants reported an annual income below C$20,000. Half (52%) had low education levels (high school or lower), 22.0% lived in single-parent households, and 52.1% lived alone. Most (62.9%) experienced at least one major financial crisis in the preceding year. CONCLUSIONS: Results show that newly registered users of food donation programs often have low-income and severe food insecurity, with major differences across geographical locations. The Pathways study is the first study designed to follow, over a 2-year period, a cohort of newly registered users of food donation programs and to quantify their trajectories of service use. Findings from the Pathways study might help adapt the community response to the strategies used by food-insecure households to feed themselves.

Accounting for antihypertensive medication in Mendelian randomization studies of blood pressure: methodological considerations in the Canadian Longitudinal Study on Aging.

BACKGROUND: Mendelian randomization (MR) studies investigating determinants of blood pressure (BP) do not account for antihypertensive medication consistently, which may explain discrepancies across studies. We performed an MR study of the association between body mass index (BMI) and systolic BP (SBP) using five methods to account for antihypertensive medication and evaluated their impact on the estimation of the causal effect and on the assessment of the invalidity of the instruments used in MR. METHODS: Baseline and follow-up data on 20 430 participants from the Canadian Longitudinal Study on Aging (CLSA) Comprehensive cohort (2011-2018) were used. The five methods to account for antihypertensive medication in the MR study were: no correction, adjustment for antihypertensive medication as a covariate in models, exclusion of treated individuals, addition of a constant value of 15 mmHg to measured values of SBP in treated individuals, and using hypertension as a binary outcome. RESULTS: The magnitude of the estimated MR causal effect for SBP (mmHg) varied across the methods of accounting for antihypertensive medication effects ranging from 0.68 (effect per 1 kg/m 2 increase in BMI) in scenario adjusting MR models for medication covariate to 1.35 in that adding 15 mmHg to measured SBP in treated individuals. Conversely, the assessment of the validity of the instruments did not differ across methods of accounting for antihypertensive medication. CONCLUSIONS: Methods to account for antihypertensive medication in MR studies may affect the estimation of the causal effects and must be selected with caution.

Identifying high school smokers likely to persist in smoking at age 31.

OBJECTIVE: Quitting smoking by the mid-30 s conveys important health benefits. Yet, although many smokers attempt to quit, few succeed. Identification of the characteristics of adolescent smokers most likely to continue smoking between ages 30 and 40 could help target early cessation efforts. Our objectives in this study were to (i) describe the course of smoking in a population-based sample of high school smokers into their 20 s and 30 s, and (ii) identify distal predictors of past-year cigarette smoking at age 31. METHODS: Data at ages 17 (in 11th grade), 20, 24 and 31 were drawn from a 20-year longitudinal study of students ages 12-13 at inception, from 10 high schools in Montréal, Canada. Associations between 11 smoking-related characteristics measured in 11th grade and past-year smoking at age 31 were estimated in multivariable logistic regression models. RESULTS: Among 244 11th grade smokers (67.4% female; 41% daily smokers), past-year smoking was reported by 71% at age 20, 68% at age 24, and 52% at age 31. Only 12% reported abstinence at ages 20, 24 and 31. Females were less likely than males to smoke at age 31. Parental smoking while the smoker was in 11th grade, use of other tobacco products, longer time since smoking onset, weekly or daily smoking, monthly cigarette consumption, and perceived nicotine addiction predicted past-year smoking at age 31. CONCLUSIONS: In addition to preventive interventions, cessation programs targeting novice smokers in high school as soon as they begin smoking, are warranted.

Predictors of Food and Physical Activity Tracking Among Young Adults.

BACKGROUND: Monitoring food intake and physical activity (PA) using tracking applications may support behavior change. However, few longitudinal studies identify the characteristics of young adults who track their behavior, findings that could be useful in designing tracking-related interventions. Our objective was to identify predictors of past-year food and PA tracking among young adults. METHODS: Data were available for 676 young adults participating in the ongoing longitudinal Nicotine Dependence in Teens Study. Potential predictors were measured in 2017-2020 at age 31, and past-year food and PA tracking were measured in 2021-2022 at age 34. Each potential predictor was studied in a separate multivariable logistic regression model controlling for age, sex, and educational attainment. RESULTS: One third (37%) of participants reported past-year PA tracking; 14% reported past-year food, and 10% reported both. Nine and 11 of 41 potential predictors were associated with food and PA tracking, respectively. Compensatory behaviors after overeating, trying to lose weight, self-report overweight, reporting a wide variety of exercise behaviors, and pressure to lose weight predicted both food and PA tracking. CONCLUSION: Food and PA tracking are relatively common among young adults. If the associations observed herein between compensatory behavior after overeating and tracking (among other observed associations) are replicated and found to be causal, caution may need to be exercised in making "blanket" recommendations to track food intake and/or PA to all young adults seeking behavior change.

The Change in Exergaming From Before to During the COVID-19 Pandemic Among Young Adults: Longitudinal Study.

BACKGROUND: Exergaming may be an important option to support an active lifestyle, especially during pandemics. OBJECTIVE: Our objectives were (1) to explore whether change in exergaming status (stopped, started or sustained exergaming, or never exergamed) from before to during the COVID-19 pandemic was related to changes in walking, moderate-to-vigorous physical activity (MVPA) or meeting MVPA guidelines and (2) to describe changes among past-year exergamers in minutes per week exergaming from before to during the pandemic. METHODS: A total of 681 participants (mean age 33.6; SD 0.5 years; n=280, 41% male) from the 22-year Nicotine Dependence in Teens (NDIT) study provided data on walking, MVPA, and exergaming before (2017 to 2020) and during (2021) the COVID-19 pandemic. Physical activity (PA) change scores were described by change in exergaming status. RESULTS: We found that 62.4% (n=425) of the 681 participants never exergamed, 8.2% (n=56) started exergaming during the pandemic, 19.7% (n=134) stopped exergaming, and 9.7% (n=66) sustained exergaming. Declines were observed in all 3 PA indicators in all 4 exergaming groups. The more salient findings were that (1) participants who started exergaming during COVID-19 reported the highest MVPA levels before and during the pandemic and declined the least (mean -35 minutes/week), (2) sustained exergamers reported the lowest MVPA levels during the pandemic (median 66 minutes/week) and declined the most in MVPA (mean change of -92 minutes/week) and in meeting MVPA guidelines (-23.6%). During the pandemic, starting exergamers reported 85 minutes of exergaming per week and sustained exergamers increased exergaming by a median 60 minutes per week. CONCLUSIONS: Although starting and sustaining exergaming did not appear to help exergamers maintain prepandemic PA levels, exergaming can contribute a substantial proportion of total PA in young adults and may still represent a useful option to promote PA during pandemics.

Factors associated with cannabis use in early adolescence. / Facteurs associés à la consommation de cannabis au début de l'adolescence.

INTRODUCTION: We examined whether factors identified as associated with cannabis use at age 14 to 16 years are also associated with ever use at age 12. METHODS: Participants in the AdoQuest study (n = 1852) were recruited in 2005 from among Grade 5 students in 29 French-language elementary schools in Montréal, Canada. Self-report data were collected from participants in Grade 5 (spring 2005) and 6 (fall 2005 and spring 2006) and from parents/guardians in 2006/07. Inclusion in the analytic sample (n = 1076; mean age [SD] = 10.7 [0.5]) required data from participant and parental questionnaires and data on cannabis use in Grade 6 (mean age [SD] = 11.7 [0.4]). We estimated associations between ever use at age 12 with 33 potential correlates, separately in unadjusted and adjusted logistic regression models. RESULTS: Fifty-three participants (4.9%) reported ever use at age 12. Factors associated with higher odds of ever use included older age, identifying as male, lower household income, more weekly spending money, ever tried cigarettes or other tobacco products, ever drank alcohol or binge drank, ever gambled, friends or siblings smoke cigarettes, greater nicotine dependence, higher depressive symptoms and greater impulsivity. Protective factors included higher levels of parental/guardian monitoring and greater self-esteem and school connectedness. CONCLUSION: Factors associated with cannabis use at later ages are also associated with ever use at age 12. Our findings suggest that surveillance for and interventions to prevent cannabis use are warranted before age 12.

Study of effect modifiers of genetically predicted CETP reduction.

Genetic variants in drug targets can be used to predict the long-term, on-target effect of drugs. Here, we extend this principle to assess how sex and body mass index may modify the effect of genetically predicted lower CETP levels on biomarkers and cardiovascular outcomes. We found sex and body mass index (BMI) to be modifiers of the association between genetically predicted lower CETP and lipid biomarkers in UK Biobank participants. Female sex and lower BMI were associated with higher high-density lipoprotein cholesterol and lower low-density lipoprotein cholesterol for the same genetically predicted reduction in CETP concentration. We found that sex also modulated the effect of genetically lower CETP on cholesterol efflux capacity in samples from the Montreal Heart Institute Biobank. However, these modifying effects did not extend to sex differences in cardiovascular outcomes in our data. Our results provide insight into the clinical effects of CETP inhibitors in the presence of effect modification based on genetic data. The approach can support precision medicine applications and help assess the external validity of clinical trials.