Measures of injury severity and prediction of acute traumatic brain injury outcomes.

OBJECTIVE: To examine the comparative efficacy of 3 common measures of traumatic brain injury (TBI) severity for predicting inpatient outcomes upon hospital discharge. SETTING: Acute brain injury rehabilitation unit at level 1 trauma center. PARTICIPANTS: 100 patients with TBI. DESIGN: Retrospective analysis of injury severity, demographic, and outcome data. MAIN MEASURES: Glasgow Coma Scale (GCS) at admission, time to follow commands (TTC), duration of posttraumatic amnesia (PTA), and Functional Independence Measure at hospital discharge. RESULTS: A hierarchal multiple regression revealed that duration of PTA was a significant and powerful unique predictor of Functional Independence Measure scores at discharge (ß = -0.46, P = .001), while TTC (ß = 0.26, P = .056) and GCS (ß = 0.16, P = .143) were not. These effects were present even after controlling for age, gender, educational level, racial/ethnic minority status, cause of injury, history of substance abuse, and neurosurgical intervention. CONCLUSION: Although clinicians often use GCS scores and TTC when assessing acute TBI severity and during treatment formulation, this study provides evidence that duration of PTA may be a more meaningful predictor of patients' functional levels at discharge.

Effectiveness of amantadine hydrochloride in the reduction of chronic traumatic brain injury irritability and aggression.

BACKGROUND: Following traumatic brain injury (TBI), individuals may experience chronic problems with irritability or aggression, which may need treatment to minimize the negative impact on their relationships, home life, social interactions, community participation, and employment OBJECTIVE: : To test the a priori hypothesis that amantadine reduces irritability (primary hypothesis) and aggression (secondary hypothesis) among individuals greater than 6 months post-TBI METHODS:: A total of 76 individuals greater than 6 months post-TBI referred for irritability management were enrolled in a parallel-group, randomized, double-blind, placebo-controlled trial of amantadine (n = 38) versus placebo (n = 38). Study participants were randomly assigned to receive amantadine hydrochloride 100 mg twice daily versus equivalent placebo for 28 days. Symptoms of irritability and aggression were measured before and after treatment using the Neuropsychiatric Inventory Irritability (NPI-I) and Aggression (NPI-A) domains, as well as the NPI-Distress for these domains RESULTS: : In the amantadine group, 80.56% improved at least 3 points on the NPI-I, compared with 44.44% in the group that received placebo (P = .0016). Mean change in NPI-I was -4.3 in the amantadine group and -2.6 in the placebo group (P = .0085). When excluding individuals with minimal to no baseline aggression, mean change in NPI-A was -4.56 in the amantadine group and -2.46 in the placebo group (P = .046). Mean changes in NPI-I and NPI-A Distress were not statistically significant between the amantadine and placebo groups. Adverse event occurrence did not differ between the 2 groups CONCLUSIONS: : Amantadine 100 mg every morning and at noon appears an effective and safe means of reducing frequency and severity of irritability and aggression among individuals with TBI and sufficient creatinine clearance.

Assessment of Seroprevalence of SARS-CoV-2 and Risk Factors Associated With COVID-19 Infection Among Outpatients in Virginia.

Importance: Data from seroepidemiologic surveys measuring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure in diverse communities and ascertaining risk factors associated with infection are important to guide future prevention strategies. Objective: To assess the prevalence of previous SARS-CoV-2 infection across Virginia and the risk factors associated with infection after the first wave of coronavirus disease 2019 (COVID-19) infections in the US. Design, Setting, and Participants: In this statewide cross-sectional surveillance study, 4675 adult outpatients presenting for health care not associated with COVID-19 in Virginia between June 1 and August 14, 2020, were recruited to participate in a questionnaire and receive venipuncture to assess SARS-CoV-2 serology. Eligibility was stratified to meet age, race, and ethnicity quotas that matched regional demographic profiles. Main Outcomes and Measures: The main outcome was SARS-CoV-2 seropositivity, as measured by the Abbott SARS-CoV-2 immunoglobulin G assay. Results: Among 4675 adult outpatients (mean [SD] age, 48.8 [16.9] years; 3119 women [66.7%]; 3098 White [66.3%] and 4279 non-Hispanic [91.5%] individuals) presenting for non-COVID-19-associated health care across Virginia, the weighted seroprevalence was 2.4% (95% CI, 1.8%-3.1%) and ranged from 0% to 20% by zip code. Seroprevalence was notably higher among participants who were Hispanic (10.2%; 95% CI, 6.1%-14.3%), residing in the northern region (4.4%; 95% CI, 2.8%-6.1%), aged 40 to 49 years (4.4%; 95% CI, 1.8%-7.1%), and uninsured (5.9%; 95% CI, 1.5%-10.3%). Higher seroprevalence was associated with Hispanic ethnicity (adjusted odds ratio [aOR], 3.56; 95% CI, 1.76-7.21), residence in a multifamily unit (aOR, 2.55; 95% CI, 1.25-5.22), and contact with an individual with confirmed COVID-19 infection (aOR, 4.33; 95% CI, 1.77-10.58). The sensitivity of serology results was 94% (95% CI, 70%-100%) among those who reported receiving a previous polymerase chain reaction test for COVID-19 infection. Among 101 participants with seropositive results, 67 individuals (66.3%) were estimated to have asymptomatic infection. These data suggested a total estimated COVID-19 burden that was 2.8-fold higher than that ascertained by PCR-positive case counts. Conclusions and Relevance: This large statewide serologic study estimated that 2.4% of adults in Virginia had exposure to SARS-CoV-2, which was 2.8-fold higher than confirmed case counts. Hispanic ethnicity, residence in a multifamily unit, and contact with an individual with confirmed COVID-19 infection were significant risk factors associated with exposure. Most infections were asymptomatic. As of August 2020, the population in Virginia remained largely immunologically naive to the virus.

Evaluation of methods for sequence analysis of highly repetitive DNA templates.

The DNA Sequencing Research Group (DSRG) of the ABRF conducted a study to assess the ability of DNA sequencing core facilities to successfully sequence a set of well-defined templates containing difficult repeats. The aim of this study was to determine whether repetitive templates could be sequenced accurately by using equipment and chemistries currently utilized in participating sequencing laboratories. The effects of primer and template concentrations, sequencing chemistries, additives, and instrument formats on the ability to successfully sequence repeat elements were examined. The first part of this study was an analysis of the results of 361 chromatograms from participants representing 40 different laboratories who attempted to sequence a panel of difficult-to-sequence templates using their best in-house protocols. The second part of this study was a smaller multi-laboratory evaluation of a single robust protocol with the same panel of templates. This study provides a measure of the potential success of different approaches to sequencing across homopolymer tracts and repetitive elements.

Amantadine Effect on Perceptions of Irritability after Traumatic Brain Injury: Results of the Amantadine Irritability Multisite Study.

This study examines the effect of amantadine on irritability in persons in the post-acute period after traumatic brain injury (TBI). There were 168 persons ≥6 months post-TBI with irritability who were enrolled in a parallel-group, randomized, double-blind, placebo-controlled trial receiving either amantadine 100 mg twice daily or equivalent placebo for 60 days. Subjects were assessed at baseline and days 28 (primary end-point) and 60 of treatment using observer-rated and participant-rated Neuropsychiatric Inventory (NPI-I) Most Problematic item (primary outcome), NPI Most Aberrant item, and NPI-I Distress Scores, as well as physician-rated Clinical Global Impressions (CGI) scale. Observer ratings between the two groups were not statistically significantly different at day 28 or 60; however, observers rated the majority in both groups as having improved at both intervals. Participant ratings for day 60 demonstrated improvements in both groups with greater improvement in the amantadine group on NPI-I Most Problematic (p<0.04) and NPI-I Distress (p<0.04). These results were not significant with correction for multiple comparisons. CGI demonstrated greater improvement for amantadine than the placebo group (p<0.04). Adverse event occurrence did not differ between the two groups. While observers in both groups reported large improvements, significant group differences were not found for the primary outcome (observer ratings) at either day 28 or 60. This large placebo or nonspecific effect may have masked detection of a treatment effect. The result of this study of amantadine 100 mg every morning and noon to reduce irritability was not positive from the observer perspective, although there are indications of improvement at day 60 from the perspective of persons with TBI and clinicians that may warrant further investigation.

Discrete gene sets depend on POU domain transcription factor Brn3b/Brn-3.2/POU4f2 for their expression in the mouse embryonic retina.

Brn3b/Brn-3.2/POU4f2 is a POU domain transcription factor that is essential for retinal ganglion cell (RGC) differentiation, axonal outgrowth and survival. Our goal was to establish a link between Brn3b and the downstream events leading to RGC differentiation. We sought to determine both the number and types of genes that depend on Brn3b for their expression. RNA probes from wild-type and Brn3b(-/-) E14.5, E16.5 and E18.5 mouse retinas were hybridized to a microarray containing 18,816 retina-expressed cDNAs. At E14.5, we identified 87 genes whose expression was significantly altered in the absence of Brn3b and verified the results by real-time PCR and in situ hybridization. These genes fell into discrete sets that encoded transcription factors, proteins associated with neuron integrity and function, and secreted signaling molecules. We found that Brn3b influenced gene expression in non RGCs of the retina by controlling the expression of secreted signaling molecules such as sonic hedgehog and myostatin/Gdf8. At later developmental stages, additional alterations in gene expression were secondary consequences of aberrant RGC differentiation caused by the absence of Brn3b. Our results demonstrate that a small but crucial fraction of the RGC transcriptome is dependent on Brn3b. The Brn3b-dependent gene sets therefore provide a unique molecular signature for the developing retina.