Recommendations for the use of common outcome measures in traumatic brain injury research

Wilde EA, Whiteneck GG, Bogner J, Bushnik T, Cifu DX, Dikmen S, French L, Giacino JT, Hart T, Malec JF, Millis SR, Novack TA, Sherer M, Tulsky DS, Vanderploeg RD, von Steinbuechel N. Recommendations for the use of common outcome measures in traumatic brain injury research.This article summarizes the selection of outcome measures by the interagency Traumatic Brain Injury (TBI) Outcomes Workgroup to address primary clinical research objectives, including documentation of the natural course of recovery from TBI, prediction of later outcome, measurement of treatment effects, and comparison of outcomes across studies. Consistent with other Common Data Elements Workgroups, the TBI Outcomes Workgroup adopted the standard 3-tier system in its selection of measures. In the first tier, core measures included valid, robust, and widely applicable outcome measures with proven utility in TBI from each identified domain, including global level of function, neuropsychological impairment, psychological status, TBI-related symptoms, executive functions, cognitive and physical activity limitations, social role participation, and perceived health-related quality of life. In the second tier, supplemental measures were recommended for consideration in TBI research focusing on specific topics or populations. In the third tier, emerging measures included important instruments currently under development, in the process of validation, or nearing the point of published findings that have significant potential to be superior to some older (“legacy”) measures in the core and supplemental lists and may eventually replace them as evidence for their utility emerges.     

First-trimester septated cystic hygroma and cavum velum interpositum cyst

First-trimester septated cystic hygroma, frequently noted during general obstetric first-trimester screening, is strongly associated with fetal aneuploidy and structural anomalies and is considered an ominous finding. We present the case of a fetus with a first-trimester septated cystic hygroma and cavum velum interpositum cyst.     

A genetic algorithm based global search strategy for population pharmacokinetic/pharmacodynamic model selection

The current algorithm for selecting a population pharmacokinetic/pharmacodynamic model is based on the well-established forward addition/backward elimination method. A central strength of this approach is the opportunity for a modeller to continuously examine the data and postulate new hypotheses to explain observed biases. This algorithm has served the modelling community well, but the model selection process has essentially remained unchanged for the last 30 years. During this time, more robust approaches to model selection have been made feasible by new technology and dramatic increases in computation speed. We review these methods, with emphasis on genetic algorithm approaches and discuss the role these methods may play in population pharmacokinetic/pharmacodynamic model selection.     

Overcoming obstacles in Parkinson's disease

Improved symptomatic and disease‐modifying treatments are needed for Parkinson's disease (PD). Although significant advances have been made in the understanding of PD etiology, the translation of these discoveries into novel transformative therapies has been limited as a result of systemic challenges in PD drug development. Preclinical testing lacks clear standards and prioritization criteria for advancing therapies to the clinic. Clinical testing is marked by expensive, long, and uninformative studies. In parallel to these scientific challenges, funding of late‐stage drug development has become increasingly scarce and risk averse. In this context, novel models of collaboration and funding are opening up new avenues for pursuing treatments. This review will discuss the most critical challenges in PD drug development and the innovative approaches being developed to overcome these hurdles. © 2012 Movement Disorder Society     

Validity Indicators Within the Wisconsin Card Sorting Test: Application of New and Previously Researched Multivariate Procedures in Multiple Traumatic Brain Injury Samples

The Wisconsin Card Sorting Test (WCST) is a popular neuropsychological measure of executive dysfunction that has been researched with regard to invalid performances, a subset of which in a forensic context could be associated with malingering. In the first of three studies, WCST multivariate approaches identified in prior research (Bernard, McGrath, & Houston, 1996; Suhr & Boyer, 1999), as well as newly created variables, were used to differentiate 33 chronic traumatic brain injury (TBI) patients with good effort and 27 patients with probable insufficient effort (IE). Newly created variables that were derived logically based upon hypotheses regarding strategies that might be employed by malingerers were not effective in differentiating TBI and IE groups. Application of previously researched validity indicators based upon commonly used WCST variables, individually, and within new logistic regression findings were reasonably effective in differentiating TBI and IE groups. In order to determine whether results would vary in different TBI samples, these validity indicators were examined in Study 2 with 75 moderate and severe, acute TBI rehabilitation patients whose posttraumatic amnesia had just resolved. Statistically significant differences were present between the IE group of Study 1 and the rehabilitation patient group of Study 2 on failures to maintain set, number of trials to achieve first correct category, and number of categories completed. All these measures were performed more poorly by the IE group. However, previously used multivariate approaches and the logistic regression analysis developed in Study 1 ranged widely in the degree to which Study 2's more acute rehabilitation patients were correctly classified. Specifically, the discriminant function of Bernard and colleagues correctly classified 73% and the Suhr and Boyer logistic regression correctly classified 75% of the Study 2 participants. The Study 1 logistic regression classified 97% of the Study 2 participants correctly. In Study 3, 130 mild to severe TBI patients in the VA system were studied. The Study 1 IE group performed significantly worse than the more acute and more severe VA TBI group on all 10 common WCST variables of interest. Application of the three multivariate procedures resulted in good to excellent classification rates: Suhr and Boyer logistic regression 85%, Bernard et al. discriminant function 85%, and Study 1 logistic regression 99%. The aggregate discussion of the three studies focuses on apparent differences in samples associated with varying degrees of success in identifying TBI patients. Application of these validity indicators in forensic situations should consider that some of these multivariate approaches possess possible classification limitations associated with chronicity and severity of the reported TBI. Only the Study 1 logistic regression demonstrated improved classification rates with the more acute and severe patients of Study 2 and Study 3. As with all validity indicators, use of any WCST IE criteria in solation would not be appropriate.     

Thickened carotid artery intima-media in rheumatoid arthritis is associated with elevated anticardiolipin antibodies

Antiphospholipid and anti-oxidized LDL (anti-oxLDL) antibodies are associated with thrombosis and atherosclerosis. Rheumatoid arthritis (RA) is characterized by excess atherosclerosis and cardiovascular diseases. Our aim was to determine whether antiphospholipid and anti-oxLDL antibodies are associated with early atherosclerotic changes in RA. The levels of IgG and IgM anticardiolipin, IgG and IgM anti-beta-2-glycoprotein-I and anti-oxLDL autoantibodies have been evaluated in 82 patients having RA. Carotid artery intima-media thickness (IMT) was measured in the carotid arteries in the common carotid, bifurcation and internal carotid arteries. Elevated levels of IgG anticardiolipin antibodies were detected in 17 of 82 (21%) RA patients, including 7 with medium-to-high levels considered being clinically relevant. These patients had significantly elevated mean carotid and carotid bifurcation IMT compared with RA patients without elevated anticardiolipin. No such association was found regarding other autoantibodies tested. Anticardiolipin antibodies are prevalent in RA and are associated with early atherosclerotic changes, supporting a rational for measuring them in RA, and upon detection treat the patients in order to decrease chances of atherosclerosis progression and thrombosis.