On Mediation Models in Clinical Neurology Studies

Cogo-Moreira, Hugo; Swardfager, Walter

doi:10.1001/jamaneurol.2018.3884

Cited by 5 publications

(3 citation statements)

References 4 publications

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“…week 12 abstinence) mediated by adherence (i.e. plasma/salivary varenicline concentrations) were estimated in SPSS Statistics, version 22 (IBM Corporation, Armonk, NY, USA) using the PROCESS macro . When estimating potential indirect effects, varenicline concentrations were standardized to Z ‐scores (i.e.…”

Section: Methodsmentioning

confidence: 99%

Impact of early nausea on varenicline adherence and smoking cessation

et al. 2019

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Background and aims Varenicline effectiveness may be related to the level of adherence, which might be reduced by adverse effects such as nausea. The aim of the study was to test a possible effect of nausea on smoking cessation outcomes mediated by adherence. Design Mediation path analysis. Setting Multiple sites within Canada and the United States. Participants Treatment‐seeking smokers receiving varenicline from two smoking cessation clinical trials: Quit2Live (NCT01836276; n = 449) and Pharmacogenetics of Nicotine Addiction Treatment (PNAT) (NCT01314001; n = 421). Measurements Nausea severity was collected through self‐report and adherence was biologically assessed using varenicline concentrations (Quit2Live, plasma sample at week 4; PNAT, saliva sample at week 2). In Quit2Live, the end‐points were cotinine‐verified abstinence at weeks 4, 12 and 26. In PNAT, the end‐points were carbon monoxide‐verified abstinence at weeks 2, 12 and 26. Findings Early nausea was not directly associated with abstinence [odds ratio (OR) ranging from 0.73–1.28; P ≥ 0.26]. However early nausea was indirectly associated with lower cessation rates at multiple timepoints (ORs ranging from 0.92–0.94; 95% CI between 0.83–0.99) in a relationship mediated by reduced varenicline adherence (assessed by plasma varenicline concentrations) in the primary trial (Quit2Live). This relationship between nausea, adherence and cessation was similar in direction but weaker in effect size (ORs ranging from 0.98–0.99; 95% CI between 0.90–1.03) in a secondary trial (PNAT), where adherence was assessed using salivary varenicline concentrations. Conclusions These data suggest that early nausea during varenicline treatment may be indirectly associated with lower likelihood of smoking cessation through reducing varenicline adherence. Differences in robustness between the trials may be due to the different biological matrices (plasma vs. saliva) and/or timing used to assess varenicline adherence. The results of the first study suggest that improved management of early nausea during varenicline treatment may positively impact smoking cessation success through increasing varenicline adherence.

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Section: Methodsmentioning

confidence: 99%

Impact of early nausea on varenicline adherence and smoking cessation

et al. 2019

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“…path c 0 ) after controlling for the mediation effect and covariates. Analyses were conducted using model 4 in PROCESS version 2.16, a macro implementation of moderation and mediation analyses for SPSS (version 27; IBM, Armonk, New York, NY) [33,34]. PROCESS was written by Dr Andrew F. Hayes.…”

Section: Mediation Path Analysismentioning

confidence: 99%

Does sex alter the relationship between CYP2B6 variation, hydroxybupropion concentration and bupropion‐aided smoking cessation in African Americans? A moderated mediation analysis

et al. 2021

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Background and Aims CYP2B6, a genetically variable enzyme, converts bupropion to its active metabolite hydroxybupropion. CYP2B6 activity and bupropion‐aided cessation differ between women and men. The aim of this study was to determine whether genetically normal (versus reduced) CYP2B6 activity increases bupropion‐aided cessation in African American smokers via higher hydroxybupropion concentration, and whether this differs by sex. Design and Setting Secondary analysis of a smoking cessation clinical trial (NCT00666978). Participants/Cases African American light smokers (≤ 10 cigarettes/day). Interventions Participants were treated with bupropion for 7 weeks. Measurements Participants with detectable bupropion and/or hydroxybupropion concentrations were divided into normal (n = 64) and reduced (n = 109) CYP2B6 activity groups based on the presence of decreased‐function CYP2B6*6 and CYP2B6*18 alleles. Biochemically verified smoking cessation was assessed at week 3, end of treatment (7 weeks) and follow‐up (26 weeks). Findings Normal (versus reduced) CYP2B6 activity was associated with increased cessation at week 7, which was mediated by higher hydroxybupropion concentration [odds ratio (OR) = 1.25, 95% confidence interval (CI) = 1.03, 1.78]; this mediation effect persisted at week 26 (OR = 1.23, 95% CI = 1.02, 1.70). The mediation effect was similar in women (n = 116; OR = 1.33, 95% CI = 1.01, 2.30) and men (n = 57; OR = 1.33, 95% CI = 0.92, 3.87). Moreover, sex did not appear to moderate the mediation effect, although this should be tested in a larger sample. Conclusions In African American light smokers with verified early bupropion use, genetically normal CYP2B6 activity appears to be indirectly associated with greater smoking cessation success in a relationship mediated by higher hydroxybupropion concentration. The mediating effect of higher hydroxybupropion concentration on smoking cessation persists beyond the active treatment phase and does not appear to differ by sex.

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“…Mediation effects between RHI, angiogenesis markers, and MoCA scores were tested using the PROCESS macro (version 3.4) for SPSS. We hypothesized an indirect effect of RHI on MoCA scores that is mediated by concentrations of the angiogenesis markers (calculated as the product of the linear regression coefficients a×b) [34]. A bias corrected inferential bootstrapping method with 10,000 permutations was used to obtain a 95% confidence interval (CI) for the indirect effect, which offers superior control of type I error compared to other methods such as the Soble test and Barron and Kenny test [35].…”

Section: Statisticsmentioning

confidence: 99%

Endostatin as a Mediator Between Endothelial Function and Cognitive Performance in Those at Risk for Vascular Cognitive Impairment

Isaacs-Trepanier

Saleem

Herrmann

et al. 2020

JAD

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Background: Patients with coronary artery disease have an increased risk for developing vascular cognitive impairment. Endothelial function is often diminished and has been associated with lower cognitive performance in these patients. The link between endothelial function and cognition in coronary artery disease is not fully understood. Angiogenesis may play a role in mediating the association between endothelial function and cognition since angiogenic processes rely heavily on the endothelium. Objective: The aim of this study was to determine if markers of angiogenesis mediate the relationship between endothelial function and cognition in coronary artery disease patients. Methods: In 50 participants with coronary artery disease, endothelial function was assessed using peripheral arterial tonometry. Vascular endothelial growth factor (pro-angiogenic) and endostatin (anti-angiogenic) were measured in peripheral serum samples. Cognition was assessed using the Montreal Cognitive Assessment. A mediation analysis, using a bias corrected inferential bootstrapping method with 10,000 permutations, was used to determine if vascular endothelial growth factor or endostatin mediated an association between peripheral arterial tonometry measures and cognitive performance on the Montreal Cognitive Assessment. Results: Endostatin, but not vascular endothelial growth factor, mediated a relationship between endothelial function and cognitive performance when controlling for total years of education, body mass index, coronary artery bypass graft, stent, diabetes, and diuretic use. This analysis was also significant when delayed recall was substituted for the overall score on the Montreal Cognitive Assessment. Conclusion: These results suggest that endostatin mediates an association between endothelial function and cognitive performance in coronary artery disease.

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On Mediation Models in Clinical Neurology Studies

Cited by 5 publications

References 4 publications

Impact of early nausea on varenicline adherence and smoking cessation

Impact of early nausea on varenicline adherence and smoking cessation

Does sex alter the relationship between CYP2B6 variation, hydroxybupropion concentration and bupropion‐aided smoking cessation in African Americans? A moderated mediation analysis

Endostatin as a Mediator Between Endothelial Function and Cognitive Performance in Those at Risk for Vascular Cognitive Impairment

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