Development of novel clinical examination scales for the measurement of disease severity in Creutzfeldt-Jakob disease

ObjectiveTo use a robust statistical methodology to develop and validate clinical rating scales quantifying longitudinal motor and cognitive dysfunction in sporadic Creutzfeldt-Jakob disease (sCJD) at the bedside.MethodsRasch analysis was used to iteratively construct interval scales measuring composite cognitive and motor dysfunction from pooled bedside neurocognitive examinations collected as part of the prospective National Prion Monitoring Cohort study, October 2008–December 2016.A longitudinal clinical examination dataset constructed from 528 patients with sCJD, comprising 1030 Motor Scale and 757 Cognitive Scale scores over 130 patient-years of study, was used to demonstrate scale utility.ResultsThe Rasch-derived Motor Scale consists of 8 items, including assessments reliant on pyramidal, extrapyramidal and cerebellar systems. The Cognitive Scale comprises 6 items, and includes measures of executive function, language, visual perception and memory. Both scales are unidimensional, perform independently of age or gender and have excellent inter-rater reliability. They can be completed in minutes at the bedside, as part of a normal neurocognitive examination. A composite Examination Scale can be derived by averaging both scores. Several scale uses, in measuring longitudinal change, prognosis and phenotypic heterogeneity are illustrated.ConclusionsThese two novel sCJD Motor and Cognitive Scales and the composite Examination Scale should prove useful to objectively measure phenotypic and clinical change in future clinical trials and for patient stratification. This statistical approach can help to overcome obstacles to assessing clinical change in rapidly progressive, multisystem conditions with limited longitudinal follow-up.

Change in Balance and Neuropsychological Measures Post-Lumbar Drain Trial in Patients with Suspected Normal Pressure Hydrocephalus

<b><i>Objective:</i></b> Ventriculoperitoneal (VP) shunting is commonly used to treat normal pressure hydrocephalus (NPH). Assessment of cognition and balance pre- and post-lumbar drain (LD) can be used to provide objective metrics which may help determine the potential benefit of VP shunting. The aim of this investigation was to determine which measures identify clinical change as a result of a LD trial and to develop recommendations for standard NPH clinical assessment procedures. <b><i>Methods:</i></b> The Berg Balance Scale (BBS) and a brief battery of commonly used neuropsychological tests pre- and post-LD (MMSE, trail making test, animal fluency, Hopkins Verbal Learning Test – Revised, and digit span) were administered to 86 patients with a diagnosis of NPH. Subjects were divided into groups based on whether or not clinical change was present, and thus, VP shunting was recommended post-LD, and predictors of group membership were examined. <b><i>Results:</i></b> Significant improvements (<i>p</i> &#x3c; 0.05) were seen on the BBS and Trail Making Part B in the VP shunt-recommended group, with no other significant changes over time in either group. Regression analyses found that VP shunt recommendation was accurately predicted for 80% of the sample using the BBS score alone, with accuracy increasing to 85% when Trails B was added. <b><i>Conclusions:</i></b> Scores from the BBS and Trails B were most likely to change in those chosen to undergo VP shunting post-LD. Given that the typical clinical presentation of NPH includes gait disturbance and cognitive impairment, it is recommended that a standard pre-/post-LD evaluation include the BBS and trail making test.

Routine Repeat Imaging of Pediatric Blunt Solid Organ Injuries Is Not Necessary

Introduction Nonoperative management of hemodynamically stable patients with blunt splenic and/or hepatic injury has been widely accepted in the pediatric population. However, variability exists in the utilization and timing of repeat imaging to assess for delayed complications during index hospitalization. Recent level-IV evidence suggests that repeat imaging in children should be performed based on a patient’s clinical status rather than on a routine basis. The aim of this study is to examine the rate of delayed complications and interventions in pediatric trauma patients with blunt splenic and/or hepatic injuries who undergo repeat imaging prompted either by a clinical change (CC) or non-clinical change (NCC). Methods A 9-year (2011-2019), retrospective, dual-institution study was performed of children (0-17 years) with blunt splenic and/or hepatic injuries. Patients were grouped based on reason for repeat imaging: CC or NCC. The rate of organ-specific delayed complications and interventions was examined by reason for scan. Results A total of 307 injuries were included in the study period (174 splenic, 113 hepatic, and 20 both). Of 194 splenic injuries, 30(15.5%) underwent repeat imaging (CC = 19; NCC = 11). Of 133 hepatic injuries, 27(20.3%) underwent repeat imaging (CC = 21; NCC = 6). There was no difference in the incidence of organ-specific delayed complications between the CC and NCC groups. Of the 4 patients with complications necessitating intervention, only one was identified based on NCC. Conclusions Our data suggest routine repeat imaging is unnecessary in children with blunt splenic and/or hepatic injuries; therefore, practitioners may rely on a patient’s clinical change.

Assessing Clinical Change in Individuals Exposed to Repetitive Head Impacts: The Repetitive Head Impact Composite Index

Background: There is a current lack of any composite measure for the effective tracking and monitoring of clinical change in individuals exposed to repetitive head impacts (RHI). The aim of this study is to create a composite instrument for the purposes of detecting change over time in cognitive and behavioral function in individuals exposed to RHI.Methods: The data to derive the composite instrument came from the Professional Fighters Brain Health Study (PFBHS), a longitudinal study of active and retired professional fighters [boxers and mixed martial arts (MMA) fighters] and healthy controls. Participants in the PFBHS underwent assessment on an annual basis that included computerized cognitive testing and behavioral questionnaires. Multivariate logistic regression models were employed to compare active fighters (n = 117) with controls (n = 22), and retired fighters (n = 26) with controls to identify the predictors that could be used to differentiate the groups over time. In a second step, linear discriminant analysis was performed to derive the linear discriminant coefficients for the three groups by using the predictors from the two separate logistic regression models.Results: The composite scale is a weighted linear value of 12 standardized scores consisting of both current and yearly change scores in domains including: processing speed, choice reaction time, semantic fluency, letter fluency, and Barrett Impulsiveness Scale. Because the weighting of values differed between active and retired fighters, two versions emerged. The mean and standard deviation ratio (MSDR) showed that the new index had better sensitivity compared to the individual measures, with the ratio of MSDR of the new index to that of the existing measures of at least 1.84.Conclusion: With the increasing need for tools to follow individuals exposed to RHI and the potential of clinical trials on the horizon for CTE, the RHICI is poised to serve as an initial approach to a composite clinical measure.

The Canadian Occupational Performance Measure: A Feasible Multidisciplinary Outcome Measure for Pediatric Telerehabilitation

This study describes the feasibility of using the Canadian Occupational Performance Measure (COPM) as a multidisciplinaryoutcome measure for pediatric telerehabilitation (TR). The COPM was administered at monthly time points over four months. A follow-up survey was conducted with the therapists to assess clinical utility of the COPM. Seventy-three percent of the children seen in TR > one month had at least two administrations of the COPM. Eighty percent of therapists agreed or strongly agreed that the COPM was easy to use in a reasonable amount of time, helped identify functional goals, could be used with various children with varied diagnoses, and measured functional change. In 37 children, the median clinical change in performance and satisfaction was two points or greater on the COPM over the episode of TR. The COPM is a feasible measure perceived positively by pediatric therapists for TR use.

Machine learning detects predictors of clinical change after Dialectical Behavior Therapy in Borderline Personality Disorder

Only 50% of the patients with Borderline Personality Disorder (BPD) respond to psychotherapies, such as Dialectical Behavioral Therapy (DBT), this might be increased by identifying baseline predictors of clinical change. We use machine learning to detect clinical features that could predict improvement/worsening for severity and impulsivity of BPD after DBT treatment. To predict illness severity, we analyzed data from 125 patients with BPD divided into 17 DBT psychotherapy groups, and for impulsiveness, we analyzed 89 patients distributed into 12 DBT groups. All patients were evaluated at baseline using widely self-report tests; ~70% of the sample were randomly selected and two machine learning models (lasso and Random forest [Rf]) were trained using 10-fold cross-validation and compared to predict the post-treatment response. Models’ generalization was assessed in ~30% of the remaining sample. Relevant variables for DBT (i.e. the mindfulness ability “non-judging”, or “non-planning” impulsiveness) measured at baseline, were robust predictors of clinical change after six months of weekly DBT sessions. Using 10-fold cross-validation, the Rf model had significantly lower prediction error than lasso for the BPD severity variable, Mean Absolute Error (MAE) lasso - Rf = 1.55 (95% CI, 0.63-2.48) as well as for impulsivity, MAE lasso - Rf = 1.97 (95% CI, 0.57 - 3.35). According to Rf and the permutations method, 34/614 significant predictors for severity and 17/614 for impulsivity were identified. Using machine learning to identify the most important clinical characteristics before starting DBT could be fundamental for personalized treatment and disease prognosis.

A Theoretically Derived Minimal Clinically Important Difference for Clinical Trials in Patients with Disorders of Consciousness

Assessing the minimal clinical change that a patient would perceive as beneficial is impossible in unconscious and non-communicative patients. We propose a novel probability-based approach to developing a minimal clinically significant change for the two most commonly used scales in patients with disorders of consciousness.