Objectives
To perform head-to-head comparisons of the feasibility and diagnostic performance of transient elastography (TE), point shear-wave elastography (pSWE), and magnetic resonance elastography ...(MRE).
Methods
This prospective, cross-sectional, dual-center imaging study included 100 patients with known or suspected chronic liver disease caused by hepatitis B or C virus, nonalcoholic fatty liver disease, or autoimmune hepatitis identified between 2014 and 2018. Liver stiffness measured with the three elastographic techniques was obtained within 6 weeks of a liver biopsy. Confounding effects of inflammation and steatosis on association between fibrosis and liver stiffness were assessed. Obuchowski scores and AUCs for staging fibrosis were evaluated and the latter were compared using the DeLong method.
Results
TE, pSWE, and MRE were technically feasible and reliable in 92%, 79%, and 91% subjects, respectively. At univariate analysis, liver stiffness measured by all techniques increased with fibrosis stages and inflammation and decreased with steatosis. For classification of dichotomized fibrosis stages, the AUCs were significantly higher for distinguishing stages F0 vs. ≥ F1 with MRE than with TE (0.88 vs. 0.71;
p
< 0.05) or pSWE (0.88 vs. 0.73;
p
< 0.05), and for distinguishing stages ≤ F1 vs. ≥ F2 with MRE than with TE (0.85 vs. 0.75;
p
< 0.05). TE, pSWE, and MRE Obuchowski scores for staging fibrosis stages were respectively 0.89 (95% CI 0.85–0.93), 0.90 (95% CI 0.85–0.94), and 0.94 (95% CI 0.91–0.96).
Conclusion
MRE provided a higher diagnostic performance than TE and pSWE for staging early stages of liver fibrosis.
Trial registration
NCT02044523
Key Points
• The technical failure rate was similar between MRE and US-based elastography techniques.
• Liver stiffness measured by MRE and US-based elastography techniques increased with fibrosis stages and inflammation and decreased with steatosis.
• MRE provided a diagnostic accuracy higher than US-based elastography techniques for staging of early stages of histology-determined liver fibrosis.
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.
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.
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.
Methods to account for antihypertensive medication in MR studies may affect the estimation of the causal effects and must be selected with caution.
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.
Background and aims
Variation in the TAS2R38 taste receptor gene alters the ability to taste bitter compounds. We tested whether TAS2R38 variation influences early smoking behaviours in adolescence, ...a critical period of acquisition when taste may influence the natural course of tobacco use.
Design and participants
Observational study (Nicotine Dependence in Teens NDIT). Cox proportional hazards models were conducted using data from European ancestry adolescent participants who initiated smoking during follow‐up (n = 219, i.e. incident smokers). In young adulthood, cross‐sectional analyses were restricted to European ancestry self‐reported current smokers at age 24 (n = 148).
Setting
Montréal, Canada.
Measurements
In adolescents, the rates of attaining early smoking milestones were estimated for tasters {PAV diplotypes (i.e. PAV/PAV or PAV/AVI)} versus non‐tasters {AVI diplotype (i.e. AVI/AVI)}. In young adults, associations between tasting status and a nicotine intake biomarker (cotinine + 3'hydroxycotinine) and past‐week cigarette consumption were assessed.
Findings
Among incident smokers, similar rates to first whole cigarette were found between the diplotype groups (hazard ratio HR, 1.05; 95% confidence interval (CI), 0.75–1.48; P = 0.765). However, smokers with the PAV (vs AVI) diplotypes attained monthly smoking more rapidly (HR, 1.55; 95% CI, 1.04–2.32; P = 0.033) and had faster conversion to three different measures of tobacco dependence (International Classification of Diseases: HR, 2.29; 95% CI, 0.99–5.28; P = 0.052; modified Fagerström Tolerance Questionnaire: HR, 3.02, 95% CI, 1.04–8.79; P = 0.043; Hooked on Nicotine Checklist: HR, 1.87; 95% CI, 0.98–3.60; P = 0.059). At age 24, those with PAV (vs AVI) diplotypes had higher mean cotinine + 3'hydroxycotinine (197 vs 143 ng/mL; P = 0.053).
Conclusions
Adolescents with a genetic variation increasing their ability to taste bitter compounds appear to escalate more quickly to monthly smoking and tobacco dependence during adolescence and have higher nicotine intake in young adulthood versus those without that genetic variation.
Abstract
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.
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.
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 (β̂95%CI = 2.12 0.34, 3.90), competence (β̂95%CI = 1.580.28, 2.88), fitness (β̂95%CI = 1.420.04, 2.80), and social (β̂95%CI = 2.321.03, 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.
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.
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).
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.
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.
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