Objectives: Long-term neurological response to treatment after a severe traumatic brain injury (sTBI) is a dynamic process. Failure to capture individual heterogeneity in recovery may impact findings from single endpoint sTBI randomized controlled trials (RCT). The present study re-examined the efficacy of erythropoietin (Epo) and transfusion thresholds through longitudinal modeling of sTBI recovery as measured by the Disability Rating Scale (DRS). This study complements the report of primary outcomes in the Epo sTBI RCT, which failed to detect significant effects of acute treatment at 6 months post-injury. Methods: We implemented mixed effects models to characterize the recovery time-course and to examine treatment efficacy as a function of time post-injury and injury severity. Results: The inter-quartile range (25th–75th percentile) of DRS scores was 20–28 at week1; 8–24 at week 4; and 3–17 at 6 months. TBI severity group was found to significantly interact with Epo randomization group on mean DRS recovery curves. No significant differences in DRS recovery were found in transfusion threshold groups. Conclusions: This study demonstrated the value of taking a comprehensive view of recovery from sTBI in the Epo RCT as a temporally dynamic process that is shaped by both treatment and injury severity, and highlights the importance of the timing of primary outcome measurement. Effects of Epo treatment varied as a function of injury severity and time. Future studies are warranted to understand the possible moderating influence of injury severity on treatment effects pertaining to sTBI recovery. (JINS, 2019, 25, 293–301)

Yoon H-K, Kim Y-K, Han C, Ko Y-H, Lee H-J, Kwon D-Y, Kim L. Paliperidone in the treatment of delirium: results of a prospective open-label pilot trial.

Objective: Delirium is a life-threatening neuropsychiatric syndrome characterised by disturbances in consciousness, attention, cognition and perception. Antipsychotics are considered the drugs of choice in managing the symptoms of delirium. Paliperidone is a benzisoxazole derivative and the principal active metabolite of risperidone. In this study, we aimed to evaluate the efficacy of paliperidone for the treatment of delirium.

Methods: A prospective open-label study of paliperidone for delirium treatment was performed with 6-day follow-up. Fifteen patients who met Diagnostic and Statistical Manual of Mental disorders, Fourth Edition criteria for delirium and had a score of 13 on the Delirium Rating Scale were recruited. The starting dose was 3 mg once a day and the dose was adjusted depending on the status of delirium. Daily assessments of the severity of delirium were evaluated using Memorial Delirium Assessment Scale (MDAS).

Results: The mean daily maintenance dose of paliperidone was 3.75 ± 1.06. The MDAS scores before and after treatment (day 7) were 23.60 ± 6.31 and 11.33 ± 5.45 (t = 6.78, p < 0.001), respectively. The intensity of delirium showed a statistically significant reduction in MDAS scores from the first day of treatment. No serious adverse effects were observed, and none of the patients discontinued paliperidone because of adverse effects.

Conclusions: This study shows that low-dose paliperidone is effective in reducing behavioural disturbances and symptoms in delirium and is well tolerated in delirious patients. This trial is an open-label study with a small sample size, and further controlled studies will be necessary.

A central role for neuropsychological evaluations is the measurement of change in cognitive functioning over time. However, change scores obtained from repeated neuropsychological assessments may be affected by normal variability because of measurement error and practice effects caused by repeated measurements. The current study uses reliable change estimates to establish normative rates of change on the Dementia Rating Scale from baseline to first follow-up testing among 1080 cognitively normal adults aged 65 and older. Results showed that a 6-point decline by European Americans or a 9-point decline by African American adults within a 9–15 month test-retest interval represents reliable change. Within a 16–24-month test-retest interval, a 7-point decline among European Americans or an 8-point decline among African American adults represents reliable change. In addition, preliminary cross-validation was performed in a clinical comparison sample of another 22 older adults. The findings are discussed in the context of potential clinical and research applications. (JINS, 2007, 13, 716–720.)

Subtraction of serial scores, Least Squares Estimators, and Best Linear Unbiased Predictors (BLUPs) were compared for estimating rates of cognitive change for Mini-Mental State Exam (MMSE) and Dementia Rating Scale (DRS) scores for 299 probable Alzheimer's disease patients. The BLUPs provided cleaner group estimates of subjects' intercepts and slopes and are preferred. Regression analysis of the BLUP estimates of rate of change indicated that steeper declines were associated with higher levels of education and older age at onset. These effects were much smaller than those due to estimated initial cognitive test score. Differences in longitudinal metric characteristics of the MMSE and DRS were found, with the DRS yielding more precise change estimates. We discuss modeling these longitudinal data, and discuss use of the estimates of rate of change and intercept as data in their own right. (JINS, 2001, 7, 813–824.)