Decreased Pain and Improved Dynamic Knee Instability Mediate the Beneficial Effect of Wearing a Soft Knee Brace on Activity Limitations in Patients With Knee Osteoarthritis

OBJECTIVE: To evaluate whether improvement of proprioception, pain or dynamic knee instability mediate the effect of wearing a soft knee brace on activity limitations in persons with knee osteoarthritis (OA). METHODS: Exploratory analysis from 44 participants with knee OA and self-reported knee instability in a laboratory trial evaluating the effect of wearing a commercially available soft knee brace. Activity limitations were assessed with the 10-meter walk test and the Get up and Go test. Knee joint proprioception was assessed by an active joint position sense test; pain was assessed with the Numeric Rating Scale (NRS); pressure pain threshold (PPT) was assessed with a hand-held pressure algometer; dynamic knee instability was expressed by the Perturbation Response, i.e. a measure reflecting a deviation in mean knee varus-valgus angle after a controlled mechanical perturbation on a treadmill, with respect to level walking. Mediation analysis was conducted with the product of coefficients approach. Confidence intervals were calculated with a bootstrap procedure. RESULTS: A decrease of pain (NRS) and a decrease of dynamic knee instability mediated the effect of wearing a soft knee brace on reduction of activity limitations (p < 0.05), while changes of proprioception and PPT did not mediate this effect (p > 0.05). CONCLUSION: This study shows that decreased pain and reduced dynamic knee instability are pathways via which wearing a soft knee brace decreased activity limitations in persons with knee OA. This article is protected by copyright. All rights reserved

Vitamin D Status and Depressive Symptoms in Older Adults:A Role for Physical Functioning?

Objectives: Depressive symptoms and low vitamin D status are common in older persons and may be associated, but findings are inconsistent. This study investigated whether 25-hydroxyvitamin D (25(OH)D) concentrations are associated with depressive symptoms in older adults, both cross-sectionally and longitudinally. We also examined whether physical functioning could explain this relationship, to gain a better understanding of the underlying mechanisms. Methods: Data from two independent prospective cohorts of the Longitudinal Aging Study Amsterdam were used: an older cohort (≥65 years, n = 1282, assessed from 1995–2002) and a younger-old cohort (55–65 years, n = 737, assessed from 2002–2009). Measurements: Depressive symptoms were measured at baseline and after 3 and 6 years with the Center of Epidemiological Studies Depression Scale. Cross-sectional and longitudinal linear regression techniques were used to examine the relationship between 25(OH)D and depressive symptoms. The mediating role of physical functioning was examined in the longitudinal models. Results: Cross-sectionally, associations were not significant after adjustment for confounders. Longitudinally, women in the older cohort with baseline 25(OH)D concentrations up to 75 nmol/L experienced 175 to 24% more depressive symptoms in the following 6 years, compared with women with 25(OH)D concentrations >75 nmol/L. Reduced physical performance partially mediated this relationship. In men and in the younger-old cohort, no significant associations were observed. Conclusions: Older women showed an inverse relationship between 25(OH)D and depressive symptoms over time, which may partially be explained by declining physical functioning. Replication of these findings by future studies is needed

Trajectories of frailty with aging:Coordinated analysis of five longitudinal studies

BACKGROUND AND OBJECTIVES: There is an urgent need to better understand frailty and its predisposing factors. Although numerous cross-sectional studies have identified various risk and protective factors of frailty, there is a limited understanding of longitudinal frailty progression. Furthermore, discrepancies in the methodologies of these studies hamper comparability of results. Here, we use a coordinated analytical approach in 5 independent cohorts to evaluate longitudinal trajectories of frailty and the effect of 3 previously identified critical risk factors: sex, age, and education. RESEARCH DESIGN AND METHODS: We derived a frailty index (FI) for 5 cohorts based on the accumulation of deficits approach. Four linear and quadratic growth curve models were fit in each cohort independently. Models were adjusted for sex/gender, age, years of education, and a sex/gender-by-age interaction term. RESULTS: Models describing linear progression of frailty best fit the data. Annual increases in FI ranged from 0.002 in the Invecchiare in Chianti cohort to 0.009 in the Longitudinal Aging Study Amsterdam (LASA). Women had consistently higher levels of frailty than men in all cohorts, ranging from an increase in the mean FI in women from 0.014 in the Health and Retirement Study cohort to 0.046 in the LASA cohort. However, the associations between sex/gender and rate of frailty progression were mixed. There was significant heterogeneity in within-person trajectories of frailty about the mean curves. DISCUSSION AND IMPLICATIONS: Our findings of linear longitudinal increases in frailty highlight important avenues for future research. Specifically, we encourage further research to identify potential effect modifiers or groups that would benefit from targeted or personalized interventions

Comparison of methods for the analysis of relatively simple mediation models

Background/aims: Statistical mediation analysis is an often used method in trials, to unravel the pathways underlying the effect of an intervention on a particular outcome variable. Throughout the years, several methods have been proposed, such as ordinary least square (OLS) regression, structural equation modeling (SEM), and the potential outcomes framework. Most applied researchers do not know that these methods are mathematically equivalent when applied to mediation models with a continuous mediator and outcome variable. Therefore, the aim of this paper was to demonstrate the similarities between OLS regression, SEM, and the potential outcomes framework in three mediation models: 1) a crude model, 2) a confounder-adjusted model, and 3) a model with an interaction term for exposure-mediator interaction. Methods: Secondary data analysis of a randomized controlled trial that included 546 schoolchildren. In our data example, the mediator and outcome variable were both continuous. We compared the estimates of the total, direct and indirect effects, proportion mediated, and 95% confidence intervals (CIs) for the indirect effect across OLS regression, SEM, and the potential outcomes framework. Results: OLS regression, SEM, and the potential outcomes framework yielded the same effect estimates in the crude mediation model, the confounder-adjusted mediation model, and the mediation model with an interaction term for exposure-mediator interaction. Conclusions: Since OLS regression, SEM, and the potential outcomes framework yield the same results in three mediation models with a continuous mediator and outcome variable, researchers can continue using the method that is most convenient to them. Keywords: Mediation analysis, Indirect effect, Ordinary least square regression, Structural equation modeling, Potential outcomes framework, Cross-sectional dat

The use of traditional and causal estimators for mediation models with a binary outcome and exposure-mediator interaction

An important recent development in mediation analysis is the use of causal mediation analysis. Causal mediation analysis decomposes the total exposure effect into causal direct and indirect effects in the presence of exposure-mediator interaction. However, in practice, traditional mediation analysis is still most widely used. The aim of this paper is to demonstrate the similarities and differences between the causal and traditional estimators for mediation models with a continuous mediator, a binary outcome, and exposure-mediator interaction. A real-life data example, analytical comparisons, and a simulation study were used to demonstrate the similarities and differences between the traditional and causal estimators. The causal and traditional estimators provide similar indirect effect estimates, but different direct and total effect estimates. Traditional mediation analysis may only be used when conditional direct effect estimates are of interest. Causal mediation analysis is the generally preferred method as its casual effect estimates help unravel causal mechanisms