Fall risk and gait in Parkinson's disease: The role of the LRRK2 G2019S mutation

Patients with Parkinson's disease (PD) who carry the G2019S mutation (a glycine to serine substitution at amino acid 2019) in the leucine‐rich repeat kinase 2 (LRRK2) gene are generally believed to be clinically indistinguishable from patients with sporadic PD. There are, however, conflicting reports on the relationship between the mutation and the motor phenotype. We quantitatively compared gait and mobility in patients with PD carriers of the G2019S mutation to non‐carrier patients with PD to better understand the genotype‐phenotype relationship. Fifty patients with PD carriers of the G2019S LRRK2 mutation and 50 age, disease duration, and disease severity matched PD non‐carriers were studied. An accelerometer quantified gait under three walking conditions: usual‐walking, dual‐tasking, and fast‐walking. The Unified Parkinson's Disease Rating Scale classified patients into PD sub‐types and the Timed Up and Go quantified mobility and fall risk. In all three walking conditions, gait variability was larger and the walking pattern was less consistent among the PD mutation carriers (P < 0.016). The PD carriers also took longer to complete the Timed Up and Go (P = 0.011) and were more likely to report having fallen in the previous year (P = 0.018). 64% of the PD carriers were classified as belonging to the postural‐instability‐gait‐difficulty (PIGD) sub‐type compared to only 17% of the PD non‐carriers (P < 0.0001). Among patients with PD, the G2019S mutation in the LRRK2 gene is apparently associated with increased gait variability, an increased fall risk, and the PIGD sub‐type. Therapeutic approach specifically designed to delay gait disturbances and falls may be justified in patients who carry the G2019S mutation. © 2013 International Parkinson and Movement Disorder Society     

Anti-stigma training and positive changes in mental illness stigma outcomes in medical students in ten countries: a mediation analysis on pathways via empathy development and anxiety reduction

Purpose

Studies of mental illness stigma reduction interventions have been criticised for failing to evaluate behavioural outcomes and mechanisms of action. This project evaluates training for medical students entitled ‘Responding to Experienced and Anticipated Discrimination’ (READ), developed to focus on skills in addition to attitudes and knowledge. We aimed to (i) evaluate the effectiveness of READ with respect to knowledge, attitudes, and clinical communication skills in responding to mental illness-related discrimination, and (ii) investigate whether its potential effectiveness was mediated via empathy or/and intergroup anxiety.

Methods

This is an international multisite non-randomised pre- vs post-controlled study. Eligible medical students were currently undertaking their rotational training in psychiatry. Thirteen sites across ten countries (n = 570) were included in the final analysis.

Results

READ was associated with positive changes in knowledge (mean difference 1.35; 95% CI 0.87 to 1.82), attitudes (mean difference − 2.50; 95% CI − 3.54 to − 1.46), skills (odds ratio 2.98; 95% CI 1.90 to 4.67), and simulated patient perceived empathy (mean difference 3.05; 95% CI 1.90 to 4.21). The associations of READ with knowledge, attitudes, and communication skills but not with simulated patient perceived empathy were partly mediated through student reported empathy and intergroup anxiety.

Conclusion

This is the first study to identify mediating effects of reduced intergroup anxiety and increased empathy in an evaluation of anti-stigma training that includes behavioural measures in the form of communication skills and perceived empathy. It shows the importance of both mediators for all of knowledge, skills, and attitudes, and hence of targeting both in future interventions.