Standardized regression-based clinical change score cutoffs for normal pressure hydrocephalus.

BACKGROUND: Presently, for patients presenting with suspected Normal Pressure Hydrocephalus (NPH) who undergo temporary drainage of cerebrospinal fluid (CSF) there is no defined model to differentiate chance improvement form clinical significance change at the individual patient level. To address this lack of information we computed standard regression based clinical change models for the 10 Meter Walk Test, Timed Up & Go, Dual Timed Up & Go, 6-Minute Walk Test, Mini-Balance Evaluation Systems Test, Montreal Cognitive Assessment, and Symbol Digit Modalities using data from patients with suspected NPH that underwent temporary drainage of CSF. These clinically significant change modes can classify clinically significant improvement following temporary drainage of CSF at the individual patient level. This allows for physicians to differentiate a clinically significant improvement in symptoms from chance improvement. METHODS: Data was collected from 323 patients, over the age of 60, with suspected NPH that underwent temporary drainage of CSF with corresponding gait and cognitive testing. McSweeney Standardized Regression Based Clinical Change Models were computed for standard gait and cognitive measures: Timed Up & Go, Dual Timed Up & Go, 10 Meter Walk Test, MiniBESTest, 6-Minute Walk Test, Montreal Cognitive Assessment, and Symbol Digit Modalities Test. To assess the discriminate validity of the measures we used correlations, Chi2, and regression analyses. RESULTS: The clinical change models explained 69-91.8% of the variability in post-drain performance (p <  0.001). As patient scores became more impaired, the percent change required for improvement to be clinically significant increased for all measures. We found that the measures were not discriminate, the Timed Up & Go was highly related to the 10 Meter Walk Test (r = 0.85, R2 = 0.769-0.738, p <  0.001), MiniBESTest (r = - 0.67, R2 = 0.589-0.734, p <  0.001), and 6 Minute Walk Test (r = - 0.77, R2 = 0.71-0.734, p <  0.001). CONCLUSION: Standardized Regression Based Clinically Significant Change Models allow for physicians to use an evidence-based approach to differentiate clinically significant change from chance improvement at the individual patient level. The Timed Up & Go was shown to be predictive of detailed measures of gait velocity, balance, and endurance.

Identifying Age Based Maturation in the ERP Response to Faces in Children With Autism: Implications for Developing Biomarkers for Use in Clinical Trials.

Recent proposals have suggested the potential for neural biomarkers to improve clinical trial processes in neurodevelopmental conditions; however, few efforts have identified whether chronological age-based adjustments will be necessary (as used in standardized behavioral assessments). Event-related potentials (ERPs) demonstrate early differences in the processing of faces vs. objects in the visual processing system by 4 years of age and age-based improvement (decreases in latency) through adolescence. Additionally, face processing has been proposed to be related to social skills as well as autistic social-communication traits. While previous reports suggest delayed latency in individuals with autism spectrum disorder (ASD), extensive individual and age based heterogeneity exists. In this report, we utilize a sample of 252 children with ASD and 118 children with typical development (TD), to assess the N170 and P100 ERP component latencies (N170L and P100L, respectively), to upright faces, the face specificity effect (difference between face and object processing), and the inversion effect (difference between face upright and inverted processing) in relation to age. First, linear mixed models (LMMs) were fitted with fixed effect of age at testing and random effect of participant, using all available data points to characterize general age-based development in the TD and ASD groups. Second, LMM models using only the TD group were used to calculate age-based residuals in both groups. The purpose of residualization was to assess how much variation in ASD participants could be accounted for by chronological age-related changes. Our data demonstrate that the N170L and P100L responses to upright faces appeared to follow a roughly linear relationship with age. In the ASD group, the distribution of the age-adjusted residual values suggest that ASD participants were more likely to demonstrate slower latencies than would be expected for a TD child of the same age, similar to what has been identified using unadjusted values. Lastly, using age-adjusted values for stratification, we found that children who demonstrated slowed age-adjusted N170L had lower verbal and non-verbal IQ and worse face memory. These data suggest that age must be considered in assessing the N170L and P100L response to upright faces as well, and these adjusted values may be used to stratify children within the autism spectrum.