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.

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.

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.

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.

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.

Does group-based trajectory modeling estimate spurious trajectories?

BACKGROUND: Group-based trajectory modelling (GBTM) is increasingly used to identify subgroups of individuals with similar patterns. In this paper, we use simulated and real-life data to illustrate that GBTM is susceptible to generating spurious findings in some circumstances. METHODS: Six plausible scenarios, two of which mimicked published analyses, were simulated. Models with 1 to 10 trajectory subgroups were estimated and the model that minimized the Bayes criterion was selected. For each scenario, we assessed whether the method identified the correct number of trajectories, the correct shapes of the trajectories, and the mean number of participants of each trajectory subgroup. The performance of the average posterior probabilities, relative entropy and mismatch criteria to assess classification adequacy were compared. RESULTS: Among the six scenarios, the correct number of trajectories was identified in two, the correct shapes in four and the mean number of participants of each trajectory subgroup in only one. Relative entropy and mismatch outperformed the average posterior probability in detecting spurious trajectories. CONCLUSION: Researchers should be aware that GBTM can generate spurious findings, especially when the average posterior probability is used as the sole criterion to evaluate model fit. Several model adequacy criteria should be used to assess classification adequacy.

Natural history and determinants of dysglycemia in Canadian children with parental obesity from ages 8-10 to 15-17 years: The QUALITY cohort.

In children, the mechanisms implicated in deterioration of glucose homeostasis versus reversion to normal glucose tolerance (NGT) remain uncertain. We aimed to describe the natural history of dysglycemia from childhood to late adolescence and to identify its early determinants. We used baseline (8-10 years, n = 630), 1st follow-up (10-12 years, n = 564) and 2nd follow-up (15-17 years, n = 377) data from the QUALITY cohort of White Canadian children with parental obesity. Children underwent a 2-h oral glucose tolerance test at each cycle with plasma glucose and insulin measured at 0/30/60/90/120 min. American Diabetes Association criteria defined dysglycemia (impaired fasting glucose, impaired glucose tolerance or type 2 diabetes). Longitudinal patterns of insulin sensitivity and beta-cell function were estimated using generalized additive mixed models. Model averaging identified biological, sociodemographic and lifestyle-related determinants of dysglycemia. Of the children NGT at baseline, 66 (21%) developed dysglycemia without reverting to NGT. Among children with dysglycemia at baseline, 24 (73%) reverted to NGT. In children with dysglycemia at 1st follow-up, 18 (53%) later reverted to NGT. Among biological, sociodemographic and lifestyle determinants at 8-10 years, only fasting and 2-h glucose were associated with developing dysglycemia (odds ratio [95% CI] per 1 mmol/L increase: 4.50 [1.06; 19.02] and 1.74 [1.11; 2.73], respectively). Beta-cell function decreased by 40% in children with overweight or obesity. In conclusion, up to 75% of children with dysglycemia reverted to NGT during puberty. Children with higher fasting and 2-h glucose were at higher risk for progression to dysglycemia, while no demographic/lifestyle determinants were identified.

Cigarette Smoking Trajectories in Adolescent Smokers: Does the Time Axis Metric Matter?

INTRODUCTION: Most studies modeling adolescent cigarette smoking trajectories use age as the time axis, possibly obscuring depiction of the natural course of cigarette smoking. We used a simulated example and real data to contrast smoking trajectories obtained from models that used time since smoking onset or calendar time (age) as the time axis. METHODS: Data were drawn from a longitudinal investigation of 1293 grade 7 students (mean age 12.8 years) recruited from 10 high schools in Montreal, Canada in 1999-2000, who were followed into young adulthood. Cigarette consumption was measured every 3 months during high school, and again at mean ages 20.4 and 24.0. Analyses using time since onset of smoking as the time metric was restricted to 307 incident smokers; analysis using calendar time included 645 prevalent and incident smokers. Smoking status and nicotine dependence (ND) were assessed at mean ages 20.4 and 24.0. Simulated data mimicked the real study during high school. RESULTS: Use of different time metrics resulted in different numbers and shapes of trajectories in the simulated and real datasets. Participants in the calendar time analyses reported more ND in young adulthood, reflecting inclusion of 388 prevalent smokers who had smoked for longer durations. CONCLUSIONS: Choosing the right time metric for trajectory analysis should be balanced against research intent. Trajectory analyses using the time since onset metric depict the natural course of smoking in incident smokers. Those using calendar time offer a snapshot of smoking across ages during a given time period. IMPLICATIONS: This study uses simulated and real data to show that trajectory analyses of cigarette smoking that use calendar time (e.g., age) versus time since onset as the time axis metric tell a different story. Trajectory analyses using the time since onset metric depict the natural course of smoking in incident smokers. Those using calendar time offer a snapshot of smoking across ages during a given time period. Choosing the right time metric should be balanced against research intent.

Physical activity motives have a direct effect on mental health.

Physical activity (PA) motives are associated with both moderate-to-vigorous intensity PA (MVPA) and mental health. Studies examining whether PA motives relate directly to mental health or indirectly through MVPA are lacking. This study examined the direct effect of five PA motives (i.e., enjoyment, competence, fitness, social, appearance) on mental health and their indirect effects through MVPA in adolescents. A total of 424 participants (57.1% females) ages 14-15 years from the longitudinal MATCH study were included. Mediation analyses, based on the counterfactual framework, assessed the natural direct effect of PA motives on mental health, and the natural indirect effects through MVPA. Separate models were conducted for each PA motive. Natural direct effects were observed for enjoyment ( ß Ì‚ [95%CI] = 2.12 [0.34, 3.90]), competence ( ß Ì‚ [95%CI] = 1.58[0.28, 2.88]), fitness ( ß Ì‚ [95%CI] = 1.42[0.04, 2.80]), and social ( ß Ì‚ [95%CI] = 2.32[1.03, 3.60]) motives. No natural direct effects were observed for appearance motives. A natural indirect effect through MVPA was observed for fitness motives, and no other natural indirect effects were found. Interventions and public health strategies in adolescents need to acknowledge the importance of enjoyment, competence social and fitness motives in PA to promote mental health, and integrate specific recommendations on the importance of the reasons why adolescents participate in PA.

Mediation by coping style in the association between stressful life events and depressive symptoms in young adults.

PURPOSE: The association between stressful life events and depressive symptoms is well-established, but the role of coping style in this association is less clear. We examined whether problem-focused, emotion-focused or avoidant coping style mediated and/or moderated the association in young adults. METHODS: Data were drawn from a 20-year longitudinal study that included 1294 students' age 12-13 years recruited in 1999-2000 from ten high schools in Montreal, Canada. Herein we report an analysis that included 782 participants aged 24 years on average with data on covariates collected at age 20. Using VanderWeele's four-way decomposition approach, the total effect of stressful life events on depressive symptoms considering coping styles was decomposed into four components: moderation only, mediation only, mediated interaction, no mediation or moderation. RESULTS: We observed mediation only by emotion-focused coping ([Formula: see text](95%CI) = 0.15(0.04, 0.24)) suggestive that individuals who experienced more stressful life events also reported greater use of emotion-focused coping and higher levels of depressive symptoms. We found moderation only by problem-focused coping ([Formula: see text](95%CI) = - 1.51(- 2.40, - 0.53)) and by emotion-focused coping ([Formula: see text](95%CI) = 1.16(0.57, 1.69). These results suggest that individuals reporting more problem-focused coping experienced fewer depressive symptoms after exposure to stressful life events; those reporting more emotion-focused coping experienced more depressive symptoms. Avoidant coping did not mediate or moderate the association between stressful life events and depressive symptoms. CONCLUSION: Interventions that aim to reduce depressive symptoms in young adults who experience stressful life events may need to reinforce problem-focused coping and minimize emotion-focused coping strategies.

Social inequalities in availability of health-promoting interventions in Québec elementary schools.

Availability of health-promoting interventions (HPIs) may vary across schools serving students with different socioeconomic backgrounds. Our objectives were to describe social inequalities across elementary schools in: (i) level of importance that school principals attribute to 13 common health-related issues among students in their school; (ii) availability of HPIs within their school addressing eight health topics and (iii) (mis)alignment between perceived importance and HPI availability. Data were collected in telephone interviews with school principals in a convenience sample of 171 elementary schools (59% of 291 schools contacted). Schools were categorized as serving very advantaged, moderately advantaged or disadvantaged students. Principals reported how important 13 health issues were among students in their schools and provided data on HPI availability for 8 health issues, 4 of which required school action under government mandates. Higher proportions of principals in schools serving disadvantaged students (36% of all 171 schools) perceived most health issues as important. The mean number of HPIs in the past year was 12.0, 12.1 and 11.7 in schools serving very advantaged, moderately advantaged and disadvantaged students, respectively. Only availability of mental health HPIs differed by school deprivation (60, 43 and 30% in very, moderately and disadvantaged, respectively). Although most schools offered oral health HPIs, dental problems were not perceived as important. Smoking was perceived as not important and smoking-related HPIs were relatively rare (9%). Given rapid evolution in public health priorities, (mis)alignment between perceived importance of specific health issues and HPI availability in elementary schools warrants ongoing reflection.

Interventions that promote health may not be present in all schools. Our objectives were to describe differences across elementary schools in: (i) level of importance that school principals attribute to common health-related issues among students in their own school; (ii) the presence of interventions that address these health issues and (iii) (mis)alignment between perceived importance and presence of interventions. Telephone interviews were conducted with school principals in 171 elementary schools serving very advantaged, moderately advantaged or disadvantaged students. Principals reported how important 13 health-related issues (four of which required school action under government mandates) were among students in their schools and whether interventions were present for 8 of the 13 issues. Higher proportions of principals in schools serving disadvantaged students perceived most health issues as important. Intervention availability did not differ across schools, except that higher proportions of schools serving advantaged students reported mental health interventions. Most schools offered oral health interventions, but dental problems were not perceived as important. Smoking was also not perceived as important and interventions were relatively rare. (Mis)alignment between perceived importance of health issues and intervention availability calls for ongoing reflection.

Intravoxel incoherent motion diffusion-weighted MRI for the characterization of inflammation in chronic liver disease.

OBJECTIVE: To evaluate the diagnostic performance of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) for grading hepatic inflammation. METHODS: In this retrospective cross-sectional dual-center study, 91 patients with chronic liver disease were recruited between September 2014 and September 2018. Patients underwent 3.0-T MRI examinations within 6 weeks from a liver biopsy. IVIM parameters, perfusion fraction (f), diffusion coefficient (D), and pseudo-diffusion coefficient (D*), were estimated using a voxel-wise nonlinear regression on DWI series (10 b-values from 0 to 800 s/mm2). The reference standard was histopathological analysis of hepatic inflammation grade, steatosis grade, and fibrosis stage. Intraclass correlation coefficients (ICC), univariate and multivariate correlation analyses, and areas under receiver operating characteristic curves (AUC) were assessed. RESULTS: Parameters f, D, and D* had ICCs of 0.860, 0.839, and 0.916, respectively. Correlations of f, D, and D* with inflammation grade were ρ = - 0.70, p < 0.0001; ρ = 0.10, p = 0.35; and ρ = - 0.27, p = 0.010, respectively. When adjusting for fibrosis and steatosis, the correlation between f and inflammation (p < 0.0001) remained, and that between f and fibrosis was also significant to a lesser extent (p = 0.002). AUCs of f, D, and D* for distinguishing inflammation grades 0 vs. ≥ 1 were 0.84, 0.53, and 0.70; ≤ 1 vs. ≥ 2 were 0.88, 0.57, and 0.60; and ≤ 2 vs. 3 were 0.86, 0.54, and 0.65, respectively. CONCLUSION: Perfusion fraction f strongly correlated, D very weakly correlated, and D* weakly correlated with inflammation. Among all IVIM parameters, f accurately graded inflammation and showed promise as a biomarker of hepatic inflammation. KEY POINTS: • IVIM parameters derived from DWI series with 10 b-values are reproducible for liver tissue characterization. • This retrospective two-center study showed that perfusion fraction provided good diagnostic performance for distinguishing dichotomized grades of inflammation. • Fibrosis is a significant confounder on the association between inflammation and perfusion fraction.

Depressive Symptoms and Cigarette Smoking in Adolescents and Young Adults: Mediating Role of Friends Smoking.

INTRODUCTION: We examined the mediating role of friends smoking in the association between depressive symptoms and daily/weekly cigarette smoking from adolescence into adulthood. METHODS: Data were drawn from the Nicotine Dependence In Teens study (NDIT, Canada) and the Avon Longitudinal Study of Parents and Children (ALSPAC, UK) studies. Three age groups were investigated in NDIT: age 13-14 (n = 1189), 15-16 (n = 1107), and 17-18 (n = 1075), and one in ALSPAC (n = 4482, age 18-21). Multivariable mediation models decomposed the total effect (TE) of depressive symptoms on smoking into a natural direct effect (NDE) and natural indirect effect (NIE) through friends smoking. RESULTS: The odds ratios (ORs) for the TE were relatively constant over time with estimates ranging from 1.12 to 1.35. Friends smoking mediated the association between depressive symptoms and smoking in the two youngest samples (OR [95% confidence interval [CI] 1.09 [1.01,1.17] in 13- to 14-year-olds; 1.10 [1.03,1.18] in 15- to 16-year-olds). In the two older samples, NDE of depressive symptoms was close to the TE, suggestive that mediation was absent or too small to detect. CONCLUSION: Friends smoking mediates the association between depressive symptoms and daily/weekly cigarette smoking in young adolescents. IMPLICATIONS: If young adolescents use cigarettes to self-medicate depressive symptoms, then interventions targeting smoking that ignore depressive symptoms may be ineffective. Our results also underscore the importance of the influence of friends in younger adolescents, suggestive that preventive intervention should target the social environment, including social relationships.

Classification and visualization of longitudinal patterns of medication dose: An application to interferon-beta-1a and amitriptyline in patients with multiple sclerosis.

PURPOSE: Describing patterns of use, including changes in dose and interruptions is challenging. Group-based trajectory modelling (GBTM) can be used to identify individuals with similar dose patterns. We provide an intuitive graphical representation of dose patterns in groups identified using GBTM. We illustrate our approach using two drugs with different combinations of available dosages. METHODS: We drew data on patients with MS followed from 1977 to 2014 in Montréal using two sub-cohorts of subjects. A sub-cohort of patients taking interferon-beta-1a and another of patients taking amitriptyline were identified from the initial cohort. We use GBTM to identify groups of patients with homogeneous dose patterns for each of the two drugs. We compared the graphical representation obtained from the fitted values of GBTM with our proposed approach, which consisted of using step functions whose values corresponded to the mode. Differences in characteristics across groups were identified using chi-squares and analysis of variance, both weighted by the posterior probability of group membership. RESULTS: Seven patterns of dose were identified for interferon-beta-1a and five for amitriptyline. The graphical representations of the patterns of dose from GBTM included values outside of the prescribed doses and did not capture changes in dose as clearly as the proposed representation using step functions. CONCLUSION: Our proposed approach which is based on the mode at each visit in each pattern provides an intuitive and realistic representation of dose patterns in groups identified with GBTM.

Self-reported weight loss attempts and weight-related stress in childhood: Heightening the risk of obesity in early adolescence.

OBJECTIVE: Weight loss attempts occur as early as childhood. The impacts of weight loss attempts and weight-related stress on the occurrence of obesity during childhood remain unknown. We aimed to: (a) assess the prevalence of self-reported weight loss attempts and weight-related stress in 8-10 year-old children and (b) determine associations with adiposity 2 years later. METHOD: Data were collected from a cohort study of 564 Canadian children aged 8-10 years, having one or both biological parents with obesity (Quebec Adipose and Lifestyle Investigation in Youth cohort). Self-reported weight loss attempts and weight-related stress were assessed at baseline in the child's questionnaire. Adiposity was measured at baseline and 2 years later using body mass index z-scores (zBMI), waist-to-height ratio (WHtR), and percentage of body fat (%BF) obtained from dual-energy x-ray absorptiometry. Linear and logistic regression analyses were used while adjusting for potential confounders. RESULTS: Forty-eight percent of children reported previous weight loss attempts and 20% reported weight-related stress. Self-reported weight loss attempts and weight-related stress were associated with higher zBMI, WHtR, and %BF 2 years later in adjusted models, although estimates were attenuated when including baseline adiposity measures. Self-reported weight loss attempts, but not weight-related stress, increased the risk of becoming overweight among children who were normal weight at baseline. DISCUSSION: Weight loss attempts are prevalent in children with parental obesity. Children reporting weight loss attempts and weight-related stress tend to have higher adiposity 2 years later and are more likely to become overweight.

Higher psychological distress in patients seeking care for a knee disorder is associated with diagnostic discordance between health care providers: a secondary analysis of a diagnostic concordance study.

BACKGROUND: Knee disorders are highly prevalent and may be a disabling condition. An accurate diagnosis is necessary to guide toward a rapid and efficient management of knee disorders. However, the ability to make a valid diagnosis is often complex for clinicians and evidence is mainly focused on clinician cognitive biases or errors produced during clinical reasoning. The aim of this secondary exploratory analysis is to identify patient-specific characteristics associated with diagnostic discordance between health care providers in making a diagnosis for a new knee disorder. METHODS: We performed a secondary analysis of a diagnostic study comparing the diagnostic ability of a physiotherapist to medical musculoskeletal specialists. Patients' socio-demographic, psychosocial and clinical characteristics were compared between the concordant and discordant diagnostic groups. Psychosocial symptoms were evaluated using the validated Kessler 6 (K6) questionnaire. We performed multivariable logistic regressions using the Bayesian Information Criterion to identify the most probable model including patients' characteristics associated with diagnostic discordance. Overall probability of identified variables to explain diagnostic discordance and associated odd ratios (OR) with 95% credibility intervals (95% CrI) were calculated. RESULTS: Overall, 279 participants were evaluated by a physiotherapist and medical musculoskeletal specialists. The mean age of the participants was 49.1 ± 15.8 years and 57.7% were female. The most common disorder was osteoarthritis (n = 117, 18.8% of cases were discordant). The most probable model explaining diagnostic discordance (11.13%) included having depressive symptoms, which was associated with an increased probability of diagnostic discordance (OR: 3.9; 95% CrI: 1.9 - 8.0) and having a higher number of comorbidities, which was associated with a decreased probability of diagnostic discordance (OR: 0.6; 95% CrI: 0.5 - 0.9). The depression item of the K6 questionnaire had a 99.4% chance to be included in a model explaining diagnostic discordance. Other variables taken separately had less than 50% chance to be included in a model explaining diagnostic discordance and cannot be considered significant. CONCLUSION: Our results suggest that depressive symptoms may increase the risk of knee diagnostic discordance. Clinicians may be more likely to make diagnostic errors and should be more cautious when evaluating patients with knee disorders suffering from psychological distress.

MRI cine-tagging of cardiac-induced motion for noninvasive staging of liver fibrosis.

BACKGROUND: MR elastography is a noninvasive technique that provides high diagnostic accuracy for the staging of liver fibrosis; however, it requires external hardware and mainly assesses the right lobe. PURPOSE: To evaluate the diagnostic performance of MRI cine-tagging for staging fibrosis in the left liver lobe, using biopsy as the reference standard. STUDY TYPE: Institutional Review Board (IRB)-approved two-center prospective study. POPULATION: Seventy-six patients with chronic liver disease who underwent an MRI cine-tagging examination and a liver biopsy within a 6-week interval. FIELD STRENGTH/SEQUENCE: 2D-GRE multislice sequence at 3.0T with spatial modulation of the magnetization preparation sequence and peripheral pulse-wave triggering on two coronal slices chosen underneath the heart apex to capture maximal deformation with consecutive breath-holds adapted to patient cardiac frequency. ASSESSMENT: A region of interest was selected in the liver close to the heart apex. Maximal strain was evaluated with the harmonic phase (HARP) technique. STATISTICAL TESTS: Spearman's correlation, Kruskal-Wallis test, Mann-Whitney U-test, and receiver operating characteristic (ROC) analysis were performed. RESULTS: Liver strain measured on tagged images decreased with higher histological fibrosis stage (ρ = -0.68, P < 0.0001). Strain values were significantly different between all fibrosis stages (P < 0.0001), and between groups of fibrosis stages ≤F3 vs. F4 (P < 0.05). Areas under the ROC curves were 0.95 (95% confidence interval: 0.89-1.00) to distinguish fibrosis stages F0 vs. F4, 0.81 (0.70-0.92) for stages F0 vs. ≥F1, 0.84 (0.76-0.93) for stages ≤F1 vs. ≥F2, 0.86 (0.78-0.94) for stages ≤F2 vs. ≥F3, and 0.87 (0.77-0.96) for stages ≤F3 vs. F4. DATA CONCLUSION: MRI cine-tagging is a promising technique for measuring liver strain without additional elastography hardware. It could be used to assess the left liver lobe as a complement to current techniques assessing the right lobe. LEVEL OF EVIDENCE: 1 Technical Efficacy: 3 J. Magn. Reson. Imaging 2020;51:1570-1580.

Mechanisms underpinning the association between physical activity and mental health in adolescence: a 6-year study.

BACKGROUND: Physical activity (PA) can promote mental health, but the mechanisms underpinning this association are not well-established. This study examined if perceptions of three basic psychological needs (autonomy, competence, relatedness) and moderate-to-vigorous physical activity (MVPA) mediate the association between number of years participating in PA and mental health in adolescence. METHODS: Participants included 937 children (55% female) age 10-11 at inception of the longitudinal MATCH study, who provided data every 4 months over 6 years. Mediation analyses were used to assess the natural direct effect of number of years of PA participation (cycles 1-15) during late childhood and adolescence on later mental health (cycle 16), measured with the Mental Health Continuum-Short Form (MHC-SF), and the natural indirect effect through each of self-perceived autonomy, competence and relatedness, and self-report MVPA (cycle 15). RESULTS: In single mediator models, indirect effects of autonomy, competence, relatedness and self-report MVPA were statistically significant. In joint mediation models (each of three models including one basic psychological need and MVPA), autonomy, competence and relatedness mediated 71, 27, and 51% of the association respectively; MVPA mediated 27-31% of the association. In the mediation model including all four mediators, relatedness mediated the largest proportion of the association, followed by autonomy and MVPA. CONCLUSION: Results support developing strategies to encourage adolescents to engage and remain involved in PA. This could foster perceptions of autonomy, competence, and relatedness as well as MVPA, which in turn may enhance mental health.

Cigarette Smoking and Nicotine Dependence Trajectories Among Incident Adolescent Smokers.

INTRODUCTION: Few interventions target adolescent cigarette smokers to prevent escalation in cigarette use or promote cessation, in part because little is known about co-developing smoking and nicotine dependence (ND). Our objectives were to: (1) estimate developmental trajectories of ND/cravings, withdrawal symptoms, the modified Fagerström Tolerance Questionnaire (mFTQ) and ICD-10 tobacco dependence in incident adolescent smokers; (2) describe concordance in number and shapes of trajectories across the four ND indicators; and (3) classify participants in each ND trajectory according to cigarette smoking trajectories. METHODS: Data were drawn from an ongoing longitudinal investigation of 1294 grade 7 students recruited in 1999-2000 in 10 Montreal-area high schools. Group-based joint trajectory models were used to identify distinct subgroups defined by the four ND indicators, in 307 incident smokers. RESULTS: The optimal trajectory model included five groups for ND/craving and four groups for each of withdrawal symptoms, the mFTQ and ICD-10 tobacco dependence. The four ND indicators showed similar developmental patterns and classification into smoking trajectory groups, although some discordance was observed. Smokers in the low-level decreaser group and stable low consumers who exhibited high ND were younger than those in the cigarette-low ND trajectory groups. Moderate or rapid escalators who exhibited no/low ND were less likely to have university-educated mothers and more likely to have parents who smoke. CONCLUSIONS: Trajectories were similar across ND indicators, and generally reflected cigarette smoking trajectory shapes. Novice smokers may need education to become self-aware of developing ND symptoms, as well as to learn about alternative courses of action once ND symptoms manifest. IMPLICATIONS: Trajectories of cigarette smoking and ND symptoms have rarely been investigated concurrently. This study provides evidence of high concordance across four distinct ND indicators in the proportion of participants with no/low-level dependence, and with high or increasing ND. Moreover, the development of cigarette smoking is concordant with ND symptom development. Interventions to prevent escalation and promote cessation should target adolescents before first puff to increase self-awareness of developing ND symptoms, as well as to learn about alternative courses of action once ND symptoms are experienced.

Type of e-liquid vaped, poly-nicotine use and nicotine dependence symptoms in young adult e-cigarette users: a descriptive study.

BACKGROUND: Data are lacking on type of e-liquid vaped among e-cigarette users. Further, few studies assess all sources of nicotine used by e-cigarette users to assess whether poly-nicotine use relates to nicotine dependence (ND). The objectives were to describe young adult e-cigarette users by: (i) type of e-liquid vaped; (ii) poly-nicotine use; (iii) ND symptoms; and (iv) attempts to quit conventional cigarettes. METHODS: Data were available in cycle 23 of a longitudinal investigation on the natural course of cigarette smoking and ND. A total of 775 young adults (44% male; mean (SD) age 30.5(1.0)) completed mailed self-report questionnaires in 2017-20. RESULTS: Of 775 participants, 149 (19.2%) reported past-year e-cigarette use. Overall, 55.0% of e-cigarette users had used cannabis-containing e-liquid (31.5% vaped cannabis e-liquid exclusively); 50.4% used nicotine-containing e-liquid (23.5% vaped nicotine e-liquid exclusively); and 39.9% used e-liquid without nicotine (8.7% vaped e-liquid without nicotine exclusively). Most e-cigarette users (82.6%) used other nicotine-containing products including conventional cigarettes (72.5%); 60.8% reported ND symptoms, rising to 79.4% among those who vaped nicotine-containing e-liquid. Finally, 29.0% tried to quit conventional cigarettes using e-cigarettes in the past-year, but only 16.7% found them helpful. CONCLUSIONS: E-cigarettes now appear to appeal to a broader market than smokers who want to quit. More than half of young adult e-cigarette users vaped cannabis-containing e-liquid in the past year while only one-quarter had used e-cigarettes to assist with cessation. Most e-cigarette users used multiple nicotine-containing substances (including combustible cigarettes) which were associated with reports of ND symptoms.