The Use of Mixed Models for the Analysis of Mediated Data with Time-Dependent Predictors

Linear mixed models (LMMs) are frequently used to analyze longitudinal data. Although these models can be used to evaluate mediation, they do not directly model causal pathways. Structural equation models (SEMs) are an alternative technique that allows explicit modeling of mediation. The goal of this paper is to evaluate the performance of LMMs relative to SEMs in the analysis of mediated longitudinal data with time-dependent predictors and mediators. We simulated mediated longitudinal data from an SEM and specified delayed effects of the predictor. A variety of model specifications were assessed, and the LMMs and SEMs were evaluated with respect to bias, coverage probability, power, and Type I error. Models evaluated in the simulation were also applied to data from an observational cohort of HIV-infected individuals. We found that when carefully constructed, the LMM adequately models mediated exposure effects that change over time in the presence of mediation, even when the data arise from an SEM

Non-linear mixed models in the analysis of mediated longitudinal data with binary outcomes

<p>Abstract</p> <p>Background</p> <p>Structural equation models (SEMs) provide a general framework for analyzing mediated longitudinal data. However when interest is in the total effect (i.e. direct plus indirect) of a predictor on the binary outcome, alternative statistical techniques such as non-linear mixed models (NLMM) may be preferable, particularly if specific causal pathways are not hypothesized or specialized SEM software is not readily available. The purpose of this paper is to evaluate the performance of the NLMM in a setting where the SEM is presumed optimal.</p> <p>Methods</p> <p>We performed a simulation study to assess the performance of NLMMs relative to SEMs with respect to bias, coverage probability, and power in the analysis of mediated binary longitudinal outcomes. Both logistic and probit models were evaluated. Models were also applied to data from a longitudinal study assessing the impact of alcohol consumption on HIV disease progression.</p> <p>Results</p> <p>For the logistic model, the NLMM adequately estimated the total effect of a repeated predictor on the repeated binary outcome and were similar to the SEM across a variety of scenarios evaluating sample size, effect size, and distributions of direct vs. indirect effects. For the probit model, the NLMM adequately estimated the total effect of the repeated predictor, however, the probit SEM overestimated effects.</p> <p>Conclusions</p> <p>Both logistic and probit NLMMs performed well relative to corresponding SEMs with respect to bias, coverage probability and power. In addition, in the probit setting, the NLMM may produce better estimates of the total effect than the probit SEM, which appeared to overestimate effects.</p

Estimating Heterogeneous Intra-class Correlation Coefficients in Dyadic Ecological Momentary Assessment

A method is described for estimating and testing predictors for influence on the variance of momentary behaviors in dyadic ecological momentary assessment data. Results show that the method allows intraclass correlations of momentary observations from two members of the same couple to vary by observation-level, individual-level and couple-level predictors

Performance of mixed effects models in the analysis of mediated longitudinal data

Backgroun: Linear mixed effects models (LMMs) are a common approach for analyzing longitudinal data in a variety of settings. Although LMMs may be applied to complex data structures, such as settings where mediators are present, it is unclear whether they perform well relative to methods for mediational analyses such as structural equation models (SEMs), which have obvious appeal in such settings. For some researchers, SEMs may be more difficult than LMMs to implement, e.g. due to lack of training in the methodology or the need for specialized SEM software. It therefore is of interest to evaluate whether the LMM performs sufficiently in a scenario particularly suitable for SEMs. We focus on evaluation of the total effect (i.e. direct and indirect) of an exposure on an outcome of interest when a mediating factor is present. Our aim is to explore whether the LMM performs as well as the SEM in a setting that is conducive to using the SEM.Methods We simulated mediated longitudinal data from an SEM where a binary, main independent variable has both direct and indirect effects on a continuous outcome. We conducted analyses with both the LMM and SEM to evaluate the performance of the LMM in a setting where the SEM is expected to be preferable. Models were evaluated with respect to bias, coverage probability and power. Sample size, effect size and error distribution of the simulated data were varied. Results: Both models performed well in a range of settings. Marginal increases in power estimates were observed for the SEM, although generally there were no major differences in performance. Power for both models was good with a sample of size of 250 and a small to medium effect size. Bias did not substantially increase for either model when data were generated from distributions that were both skewed and kurtotic. Conclusions: In settings where the goal is to evaluate the overall effects, the LMM excluding mediating variables appears to have good performance with respect to power, bias and coverage probability relative to the SEM. The major benefit of SEMs is that it simultaneously and efficiently models both the direct and indirect effects of the mediation process

Duration of symptoms resulting from lumbar disc herniation: effect on treatment outcomes: analysis of the Spine Patient Outcomes Research Trial (SPORT).

BACKGROUND: The purpose of the present study was to determine if the duration of symptoms affects outcomes following the treatment of intervertebral lumbar disc herniation. METHODS: An as-treated analysis was performed on patients enrolled in the Spine Patient Outcomes Research Trial (SPORT) for the treatment of intervertebral lumbar disc herniation. Randomized and observational cohorts were combined. A comparison was made between patients who had had symptoms for six months or less (n = 927) and those who had had symptoms for more than six months (n = 265). Primary and secondary outcomes were measured at baseline and at regular follow-up intervals up to four years. The treatment effect for each outcome measure was determined at each follow-up period for the duration of symptoms for both groups. RESULTS: At all follow-up intervals, the primary outcome measures were significantly worse in patients who had had symptoms for more than six months prior to treatment, regardless of whether the treatment was operative or nonoperative. When the values at the time of the four-year follow-up were compared with the baseline values, patients in the operative treatment group who had had symptoms for six months or less had a greater increase in the bodily pain domain of the Short Form-36 (SF-36) (mean change, 48.3 compared with 41.9; p \u3c 0.001), a greater increase in the physical function domain of the SF-36 (mean change, 47.7 compared with 41.2; p \u3c 0.001), and a greater decrease in the Oswestry Disability Index score (mean change, -41.1 compared with -34.6; p \u3c 0.001) as compared with those who had had symptoms for more than six months (with higher scores indicating less severe symptoms on the SF-36 and indicating more severe symptoms on the Oswestry Disability Index). When the values at the time of the four-year follow-up were compared with the baseline values, patients in the nonoperative treatment group who had had symptoms for six months or less had a greater increase in the bodily pain domain of the SF-36 (mean change, 31.8 compared with 21.4; p \u3c 0.001), a greater increase in the physical function domain of the SF-36 (mean change, 29.5 compared with 22.6; p = 0.015), and a greater decrease in the Oswestry Disability Index score (mean change, -24.9 compared with -18.5; p = 0.006) as compared with those who had had symptoms for more than six months. Differences in treatment effect between the two groups related to the duration of symptoms were not significant. CONCLUSIONS: Increased symptom duration due to lumbar disc herniation is related to worse outcomes following both operative and nonoperative treatment. The relative increased benefit of surgery compared with nonoperative treatment was not dependent on the duration of the symptoms

Sexual Orientation Disparities in BMI among US Adolescents and Young Adults in Three Race/Ethnicity Groups

Obesity is a key public health issue for US youth. Previous research with primarily white samples of youth has indicated that sexual minority females have higher body mass index (BMI) and sexual minority males have lower BMI than their same-gender heterosexual counterparts, with sexual orientation differences in males increasing across adolescence. This research explored whether gender and sexual orientation differences in BMI exist in nonwhite racial/ethnic groups. Using data from Waves I–IV (1995–2009) of the US National Longitudinal Study of Adolescent Health (N = 13,306, ages 11–34 years), we examined associations between sexual orientation and BMI (kg/m2) over time, using longitudinal linear regression models, stratified by gender and race/ethnicity. Data were analyzed in 2013. Among males, heterosexual individuals showed greater one-year BMI gains than gay males across all race/ethnicity groups. Among females, white and Latina bisexual individuals had higher BMI than same-race/ethnicity heterosexual individuals regardless of age; there were no sexual orientation differences in black/African Americans. Sexual orientation disparities in BMI are a public health concern across race/ethnicity groups. Interventions addressing unhealthy weight gain in youth must be relevant for all sexual orientations and race/ethnicities

Effect of the Planet Health Intervention on Eating Disorder Symptoms in Massachusetts Middle Schools, 2005–2008

Introduction: The Planet Health obesity prevention curriculum has prevented purging and abuse of diet pills (disordered weight control behavior [DWCB]) in middle-school girls in randomized trials, but the effects of Planet Health on DWCB when implemented by schools under dissemination conditions are not known. Methods: Massachusetts Department of Public Health and Blue Cross Blue Shield of Massachusetts disseminated Planet Health as part of the 3-year, Healthy Choices obesity prevention program in middle schools. We conducted an evaluation in 45 schools from fall 2005 to spring 2008. We gathered data from school staff to quantify intervention activities, and we gathered anonymous cross-sectional survey data from students on DWCB at baseline and Year 3 follow-up (n = 16,369). Multivariate logistic analyses with generalized estimating equations examined the effect of intervention activities on odds of students reporting DWCB at follow-up. Results: Students in schools reaching a high number of youth with Planet Health lessons on reducing television viewing had lower odds of DWCB at follow-up (odds ratio [OR], 0.80 per 100 lesson-exposures; 95% confidence interval [CI], 0.74–0.85). In addition, reduced odds of DWCB at follow-up were found in schools with active staff teamwork (OR, 0.76; 95% CI, 0.66–0.86) and the presence of programs addressing television viewing goals with staff (OR, 0.38; 95% CI, 0.28–0.53). Conclusion: Combined evidence from efficacy and effectiveness trials and now from dissemination research indicates that appropriately designed obesity prevention programs can achieve DWCB prevention on a large scale

Effect of the planet health intervention on eating disorder symptoms in Massachusetts middle schools, 2005-2008

INTRODUCTION: The Planet Health obesity prevention curriculum has prevented purging and abuse of diet pills (disordered weight control behavior [DWCB]) in middle-school girls in randomized trials, but the effects of Planet Health on DWCB when implemented by schools under dissemination conditions are not known. METHODS: Massachusetts Department of Public Health and Blue Cross Blue Shield of Massachusetts disseminated Planet Health as part of the 3-year, Healthy Choices obesity prevention program in middle schools. We conducted an evaluation in 45 schools from fall 2005 to spring 2008. We gathered data from school staff to quantify intervention activities, and we gathered anonymous cross-sectional survey data from students on DWCB at baseline and Year 3 follow-up (n = 16,369). Multivariate logistic analyses with generalized estimating equations examined the effect of intervention activities on odds of students reporting DWCB at follow-up. RESULTS: Students in schools reaching a high number of youth with Planet Health lessons on reducing television viewing had lower odds of DWCB at follow-up (odds ratio [OR], 0.80 per 100 lesson-exposures; 95% confidence interval [CI], 0.74-0.85). In addition, reduced odds of DWCB at follow-up were found in schools with active staff teamwork (OR, 0.76; 95% CI, 0.66-0.86) and the presence of programs addressing television viewing goals with staff (OR, 0.38; 95% CI, 0.28-0.53). CONCLUSION: Combined evidence from efficacy and effectiveness trials and now from dissemination research indicates that appropriately designed obesity prevention programs can achieve DWCB prevention on a large scale

Surgical versus nonsurgical therapy for lumbar spinal stenosis.

BACKGROUND: Surgery for spinal stenosis is widely performed, but its effectiveness as compared with nonsurgical treatment has not been shown in controlled trials. METHODS: Surgical candidates with a history of at least 12 weeks of symptoms and spinal stenosis without spondylolisthesis (as confirmed on imaging) were enrolled in either a randomized cohort or an observational cohort at 13 U.S. spine clinics. Treatment was decompressive surgery or usual nonsurgical care. The primary outcomes were measures of bodily pain and physical function on the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36) and the modified Oswestry Disability Index at 6 weeks, 3 months, 6 months, and 1 and 2 years. RESULTS: A total of 289 patients were enrolled in the randomized cohort, and 365 patients were enrolled in the observational cohort. At 2 years, 67% of patients who were randomly assigned to surgery had undergone surgery, whereas 43% of those who were randomly assigned to receive nonsurgical care had also undergone surgery. Despite the high level of nonadherence, the intention-to-treat analysis of the randomized cohort showed a significant treatment effect favoring surgery on the SF-36 scale for bodily pain, with a mean difference in change from baseline of 7.8 (95% confidence interval, 1.5 to 14.1); however, there was no significant difference in scores on physical function or on the Oswestry Disability Index. The as-treated analysis, which combined both cohorts and was adjusted for potential confounders, showed a significant advantage for surgery by 3 months for all primary outcomes; these changes remained significant at 2 years. CONCLUSIONS: In the combined as-treated analysis, patients who underwent surgery showed significantly more improvement in all primary outcomes than did patients who were treated nonsurgically. (ClinicalTrials.gov number, NCT00000411 [ClinicalTrials.gov].)