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This study introduces a special series on validity studies of the Cognition Battery (CB) from the U.S. National Institutes of Health Toolbox for the Assessment of Neurological and Behavioral Function (NIHTB) (Gershon, Wagster et al., 2013) in an adult sample. This first study in the series describes the sample, each of the seven instruments in the NIHTB-CB briefly, and the general approach to data analysis. Data are provided on test-retest reliability and practice effects, and raw scores (mean, standard deviation, range) are presented for each instrument and the gold standard instruments used to measure construct validity. Accompanying papers provide details on each instrument, including information about instrument development, psychometric properties, age and education effects on performance, and convergent and discriminant construct validity. One study in the series is devoted to a factor analysis of the NIHTB-CB in adults and another describes the psychometric properties of three composite scores derived from the individual measures representing fluid and crystallized abilities and their combination. The NIHTB-CB is designed to provide a brief, comprehensive, common set of measures to allow comparisons among disparate studies and to improve scientific communication.

Cognition is 1 of 4 domains measured by the NIH Toolbox for the Assessment of Neurological and Behavioral Function (NIH-TB), and complements modules testing motor function, sensation, and emotion. On the basis of expert panels, the cognition subdomains identified as most important for health, success in school and work, and independence in daily functioning were Executive Function, Episodic Memory, Language, Processing Speed, Working Memory, and Attention. Seven measures were designed to tap constructs within these subdomains. The instruments were validated in English, in a sample of 476 participants ranging in age from 3 to 85 years, with representation from both sexes, 3 racial/ethnic categories, and 3 levels of education. This report describes the development of the Cognition Battery and presents results on test-retest reliability, age effects on performance, and convergent and discriminant construct validity. The NIH-TB Cognition Battery is intended to serve as a brief, convenient set of measures to supplement other outcome measures in epidemiologic and longitudinal research and clinical trials. With a computerized format and national standardization, this battery will provide a "common currency" among researchers for comparisons across a wide range of studies and populations.

Background: MEK is a member of the MAPK signalling cascade that is commonly activated in melanoma. Direct inhibition of MEK blocks cell proliferation and induces apoptosis. We aimed to analyse safety, efficacy, and genotyping data for the oral, small-molecule MEK inhibitor trametinib in patients with melanoma., Methods: We undertook a multicentre, phase 1 three-part study (dose escalation, cohort expansion, and pharmacodynamic assessment). The main results of this study are reported elsewhere; here we present data relating to patients with melanoma. We obtained tumour samples to assess BRAF mutational status, and available tissues underwent exploratory genotyping analysis. Disease response was measured by Response Evaluation Criteria in Solid Tumors, and adverse events were defined by common toxicity criteria. This study is registered with ClinicalTrials.gov, number NCT00687622., Findings: 97 patients with melanoma were enrolled, including 81 with cutaneous or unknown primary melanoma (36 BRAF mutant, 39 BRAF wild-type, six BRAF status unknown), and 16 with uveal melanoma. The most common treatment-related adverse events were rash or dermatitis acneiform (n=80; 82%) and diarrhoea (44; 45%), most of which were grade 2 or lower. No cutaneous squamous-cell carcinomas were recorded. Of 36 patients with BRAF mutations, 30 had not received a BRAF inhibitor before; two complete responses (both confirmed) and ten partial responses (eight confirmed) were noted in this subgroup (confirmed response rate, 33%). Median progression-free survival of this subgroup was 5·7 months (95% CI 4·0-7·4). Of the six patients who had received previous BRAF inhibition, one unconfirmed partial response was recorded. Of 39 patients with BRAF wild-type melanoma, four partial responses were confirmed (confirmed response rate, 10%)., Interpretation: Our data show substantial clinical activity of trametinib in melanoma and suggest that MEK is a valid therapeutic target. Differences in response rates according to mutations indicate the importance of mutational analyses in the future., Funding: GlaxoSmithKline., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: To describe the development and calibration of the banks and scales of the Quality of Life in Neurological Disorders (Neuro-QOL) project, commissioned by the National Institute of Neurological Disorders and Stroke to develop a bilingual (English/Spanish), clinically relevant, and psychometrically robust health-related quality-of-life (HRQOL) assessment tool., Design: Classic and modern test construction methods were used, including input from essential stakeholder groups., Setting: An online patient panel testing service and 11 academic medical centers and clinics from across the United States and Puerto Rico that treat major neurologic disorders., Participants: Adult and pediatric patients representing different neurologic disorders specified in this study, proxy respondents for select conditions (stroke, pediatric conditions), and English- and Spanish-speaking participants from the general population., Interventions: Not applicable., Main Outcome Measures: Multiple generic and condition-specific measures used to provide construct validity evidence for the new Neuro-QOL tool., Results: Neuro-QOL has developed 14 generic item banks and 8 targeted scales to assess HRQOL in 5 adult (stroke, multiple sclerosis, Parkinson's disease, epilepsy, amyotrophic lateral sclerosis) and 2 pediatric conditions (epilepsy, muscular dystrophies)., Conclusions: The Neuro-QOL system will continue to evolve, with validation efforts in clinical populations and new bank development in health domains not presently included. The potential for Neuro-QOL measures in rehabilitation research and clinical settings is discussed., (Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Stroke mortality is higher in the "Stroke Belt" and among blacks in the United States. Because hypertension is the leading risk factor for stroke, hypertension management (raising awareness, increasing treatment, and improving control) may reduce these disparities., Methods: Hypertension awareness, treatment, and control were measured in the REasons for Geographic And Racial Differences in Stroke study, a national population-based cohort of black and white participants >45 years of age. At the time of this report, 11,701 had been enrolled. Racial differences and geographic differences (between the Stroke Belt and other regions of the United States) were described., Results: Black participants were more aware than whites of their hypertension (odds ratio [OR], 1.31; 95% CI, 1.07 to 1.59) and more likely to be on treatment if aware of their diagnosis (OR, 1.69; 95% CI, 1.40 to 2.05), but among those treated for hypertension, they were less likely than whites to have their blood pressure controlled (OR, 0.73; 95% CI, 0.64 to 0.83). There was no evidence of a difference between the Stroke Belt and other regions in awareness of hypertension (OR, 0.95; 95% CI, 0.79 to 1.14), but there was a trend for better treatment (OR, 1.15; 95% CI, 0.97 to 1.37) and control (OR, 1.11; 95% CI, 0.98 to 1.30) in the Stroke Belt region., Conclusions: These findings suggest that interventions to improve blood pressure control among blacks are promising to reduce the racial disparity in stroke mortality. The lack of substantial geographic differences in hypertension awareness and the trend toward better treatment and control in the Stroke Belt suggest that differences in hypertension management may not be a major contributor to the geographic disparity in stroke mortality.

Objectives: To report initial mortality findings from the Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of iodine 125 brachytherapy vs enucleation for treatment of choroidal melanoma., Methods: Patients were evaluated for eligibility at 43 participating clinical centers in the United States and Canada. Eligible consenting patients were assigned randomly at the time of enrollment to enucleation or 125I brachytherapy. Patients were examined at specified intervals after enrollment for data collection purposes. Findings presented herein are based on data received by September 30, 2000. Data for each patient were analyzed with the treatment group to which the patient was assigned randomly at the time of enrollment., Results: During the 11(1/2)-year accrual period, 1317 patients enrolled; 660 were assigned randomly to enucleation and 657 to 125I brachytherapy. Only 2 patients in the enucleation arm were found to have been misdiagnosed when histopathology was reviewed centrally. All but 17 patients (1.3%) received the assigned treatment. Adherence to the brachytherapy protocol was excellent, with 91% of patients treated per protocol. Based on time since enrollment, 1072 patients (81%) had been followed for mortality for 5 years and 416 (32%) for 10 years. A total of 364 patients had died: 188 (28%) of 660 patients in the enucleation arm and 176 (27%) of 657 patients in the brachytherapy arm. The unadjusted estimated 5-year survival rates were 81% and 82%, respectively; there was no clinically or statistically significant difference in survival rates overall (P =.48, log-rank test). The adjusted estimated risk ratio for 125I brachytherapy vs enucleation was 0.99 (95% confidence interval [CI], 0.80-1.22). Five-year rates of death with histopathologically confirmed melanoma metastasis were 11% and 9% following enucleation and brachytherapy, respectively; after adjustment, the estimated risk ratio was 0.91 (95% CI, 0.66-1.24)., Conclusions: Mortality rates following 125I brachytherapy did not differ from mortality rates following enucleation for up to 12 years after treatment of patients with choroidal melanoma who enrolled in this COMS trial. The power of the study was sufficient to indicate that neither treatment is likely to increase or decrease mortality rates by as much as 25% relative to the other.

Ascertainment of cause of death is often sought in clinical trials in which mortality is an outcome of interest. Standardized methods of coding all-cause and disease-specific mortality were developed and evaluated in the Collaborative Ocular Melanoma Study randomized trial of pre-enucleation radiation of large choroidal melanoma. All available clinical and pathologic materials documenting events prior to each reported death were reviewed systematically by a Mortality Coding Committee (MCC) to determine whether melanoma metastasis or local recurrence was present at the time of death. A level of certainty was assigned based on availability of local or central review of pathology materials. The outcome of the mortality coding protocol was evaluated both by assessing agreement between the judgment of the MCC and the presumed cause of death reported by the clinical center and, for a subset of patients, by assessing agreement between the MCC classification and the cause of death reported on the death certificate. As of July 31, 1997 (the cutoff date for the initial mortality report), 435 (95%) of 457 deceased patient files had been reviewed. The MCC classified 269 patients (62%) as dead with melanoma metastasis, 22 (5%) as dead with another malignant tumor, and 92 (21%) as dead with a malignant tumor of uncertain origin. Thirty-eight patients (9%) died with no evidence of malignancy; in 14 cases (3%), the presence or absence of malignancy could not be established due to lack of clinical information. Fair agreement (kappa = 0.34) was observed between the determinations of the MCC based on detailed review of materials and the cause of death reported on the death certificate, but death certificates alone underestimated the proportion of deaths due to metastatic choroidal melanoma. Detailed mortality coding identified difficulties associated with accurate reporting of cause-specific mortality in patients with choroidal melanoma.