Many patients with social anxiety disorder (SAD) experience inadequate symptom relief from available treatments. Ketamine is a potent N-methyl-D-aspartate receptor antagonist with a potentially novel ...mechanism of action for the treatment of anxiety disorders. Therefore, we conducted a double-blind, randomized, placebo-controlled crossover trial in 18 adults with DSM-5 SAD and compared the effects between intravenous ketamine (0.5 mg/kg over 40 min) and placebo (normal saline) on social phobia symptoms. Ketamine and placebo infusions were administered in a random order with a 28-day washout period between infusions. Ratings of anxiety were assessed 3-h post-infusion and followed for 14 days. We used linear mixed models to assess the impact of ketamine and placebo on anxiety symptoms. Outcomes were blinded ratings on the Liebowitz Social Anxiety Scale (LSAS) and self-reported anxiety on a visual analog scale (VAS-Anxiety). We also used the Wilcoxon signed-rank test to compare the proportion of treatment responders. Based on prior studies, we defined response as a greater than 35% LSAS reduction and 50% VAS-Anxiety reduction. We found ketamine resulted in a significantly greater reduction in anxiety relative to placebo on the LSAS (Time × Treatment: F
=2.6, p=0.01) but not the VAS-Anxiety (Time × Treatment: F
=0.4, p=0.95). Participants were significantly more likely to exhibit a treatment response after ketamine infusion relative to placebo in the first 2 weeks following infusion measured on the LSAS (33.33% response ketamine vs 0% response placebo, Wilcoxon signed-rank test z=2.24, p=0.025) and VAS (88.89% response ketamine vs 52.94% response placebo, Wilcoxon signed-rank test z=2.12, p=0.034). In conclusion, this proof-of-concept trial provides initial evidence that ketamine may be effective in reducing anxiety.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To explore predictors of 8-year school-based behavioral outcomes in attention-deficit/hyperactivity disorder (ADHD).
We examined potential baseline predictors of school-based behavioral outcomes in ...children who completed the 8-year follow-up in the multimodal treatment study of children with ADHD. Stepwise logistic regression and receiver operating characteristic (ROC) analysis identified baseline predictors that were associated with a higher risk of truancy, school discipline, and in-school fights.
Stepwise regression analysis explained between 8.1% (in-school fights) and 12.0% (school discipline) of the total variance in school-based behavioral outcomes. Logistic regression identified several baseline characteristics that were associated with school-based behavioral difficulties 8 years later, including being male (associated with truancy and school discipline), African American (school discipline, in-school fights), increased conduct disorder (CD) symptoms (truancy), decreased affection from parents (school discipline), ADHD severity (in-school fights), and study site (truancy and school discipline). ROC analyses identified the most discriminative predictors of truancy, school discipline, and in-school fights, which were Aggression and Conduct Problem Scale Total score, family income, and race, respectively.
A modest, but nontrivial portion of school-based behavioral outcomes, was predicted by baseline childhood characteristics. Exploratory analyses identified modifiable (lack of paternal involvement, lower parental knowledge of behavioral principles, and parental use of physical punishment), somewhat modifiable (income and having comorbid CD), and nonmodifiable (African American and male) factors that were associated with school-based behavioral difficulties. Future research should confirm that the associations between earlier specific parenting behaviors and poor subsequent school-based behavioral outcomes are, indeed, causally related and independent cooccurring childhood psychopathology. Future research might target increasing paternal involvement and parental knowledge of behavioral principles and reducing use of physical punishment to improve school-based behavioral outcomes in children with ADHD.
School refusal is an important pediatric problem with significant negative short- and long-term outcomes. Specific psychosocial treatments appear effective in reducing school refusal, but many ...children do not respond to these treatments. Although systematic reviews have examined the efficacy of psychological interventions for school refusal, no systematic reviews on pharmacological interventions exist.
We conducted a comprehensive literature search of MEDLINE, PsycINFO, Scopus, and Embase for randomized controlled trials (RCTs) or quasi-experimental pharmacologic trials in children and adolescents with school refusal reported in English or Spanish until July 1, 2017. Two authors screened study titles and abstracts for eligibility. Data regarding the population, intervention, comparison, and outcomes for each trial were extracted and reported. Effect sizes for school attendance are presented.
The search identified 6 articles, including 7 trials (6 RCTs and 1 open label) and 306 youths. Pharmacologic treatments investigated for school refusal included antidepressants (imipramine, clomipramine, and fluoxetine) and benzodiazepines (alprazolam). All pharmacotherapies studied had pretreatment to posttreatment improvements on school refusal, depression, and anxiety symptoms. However, included trials were severely underpowered and did not demonstrate significant improvement compared to placebo.
Data regarding pharmacological treatments for school refusal are sparse. Most trials in this area were conducted before development of newer antidepressants, were underpowered, and have significant methodological limitations that are characteristic of the time in which they were conducted. This systematic review highlights the need for more trials with newer pharmacologic agents, larger sample sizes, and improved systematic assessments of school refusal and comorbidities. School refusal represents an important functional outcome for many children, especially those with anxiety and depression. Future pharmacologic studies of anxiety and depression in children may benefit from incorporating specific school refusal measures as secondary outcomes.
This study examines predictors of later risky driving behavior in children with attention-deficit/hyperactivity disorder (ADHD).
Stepwise logistic regression and receiver operating characteristic ...(ROC) analysis were used to explore baseline predictors of risky driving behavior for adolescents who completed the 8-year follow-up assessment in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (MTA).
Stepwise logistic regression analysis explained 19% of the total variance in risky driving behavior. Increased likelihood of risky driving behavior was associated with parental history of conduct disorder, low parental monitoring and supervision, and increased age. ROC analysis identified discriminative predictors for adolescents older and younger than 16 years of age at follow-up. The most discriminative predictors of later risky driving behavior were parental stress at baseline (for children 16 years or older) and increased child-rated parental protectiveness (for children less than 16 years old).
Risky driving behavior was significantly predicted by baseline characteristics for the MTA cohort. Aspects of parenting behavior (or the child's perception of them), including parental stress levels, parental protectiveness, and parental levels of monitoring and supervision, were most informative in predicting these outcomes. Our results suggest that interventions to reduce high-risk behaviors in these high-risk children with ADHD might involve targeted parenting interventions.
To develop new diagnostic criteria for mild traumatic brain injury (TBI) that are appropriate for use across the lifespan and in sports, civilian trauma, and military settings.
Rapid evidence reviews ...on 12 clinical questions and Delphi method for expert consensus.
The Mild Traumatic Brain Injury Task Force of the American Congress of Rehabilitation Medicine Brain Injury Special Interest Group convened a Working Group of 17 members and an external interdisciplinary expert panel of 32 clinician-scientists. Public stakeholder feedback was analyzed from 68 individuals and 23 organizations.
The first 2 Delphi votes asked the expert panel to rate their agreement with both the diagnostic criteria for mild TBI and the supporting evidence statements. In the first round, 10 of 12 evidence statements reached consensus agreement. Revised evidence statements underwent a second round of expert panel voting, where consensus was achieved for all. For the diagnostic criteria, the final agreement rate, after the third vote, was 90.7%. Public stakeholder feedback was incorporated into the diagnostic criteria revision prior to the third expert panel vote. A terminology question was added to the third round of Delphi voting, where 30 of 32 (93.8%) expert panel members agreed that 'the diagnostic label 'concussion' may be used interchangeably with 'mild TBI' when neuroimaging is normal or not clinically indicated.'
New diagnostic criteria for mild TBI were developed through an evidence review and expert consensus process. Having unified diagnostic criteria for mild TBI can improve the quality and consistency of mild TBI research and clinical care.
Repetitive head impact exposure sustained by athletes of contact sports has been hypothesized to be a mechanism for concussion and a possible explanation for the high degree of variability in ...sport-related concussion biomechanics. In an attempt to limit repetitive head impact exposure during the football preseason, the NCAA eliminated two-a-day practices in 2017, while maintaining the total number of team practice sessions. The objective of this study was to quantify head impact exposure during the preseason and regular season in Division I college football athletes to determine whether the 2017 NCAA ruling decreased head impact exposure. 342 unique athletes from five NCAA Division I Football Bowl Subdivision (FBS) programs were consented and enrolled. Head impacts were recorded using the Head Impact Telemetry (HIT) System during the entire fall preseasons and regular seasons in 2016 and 2017. Despite the elimination of two-a-day practices, the number of preseason contact days increased in 2017, with an increase in average hourly impact exposure (i.e., contact intensity), resulting in a significant increase in total head impact burden (+ 26%) for the 2017 preseason. This finding would indicate that the 2017 NCAA ruling was not effective at reducing the head impact burden during the football preseason. Additionally, athletes sustained a significantly higher number of recorded head impacts per week (+ 40%) during the preseason than the regular season, implicating the preseason as a time of elevated repetitive head impact burden. With increased recognition of a possible association between repetitive head impact exposure and concussion, increased preseason exposure may predispose certain athletes to a higher risk of concussion during the preseason and regular season. Accordingly, efforts at reducing concussion incidence in contact sports should include a reduction in overall head impact exposure.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Studies of football athletes have implicated repetitive head impact exposure in the onset of cognitive and brain structural changes, even in the absence of diagnosed concussion. Those studies imply ...accumulating damage from successive head impacts reduces tolerance and increases risk for concussion. Support for this premise is that biomechanics of head impacts resulting in concussion are often not remarkable when compared to impacts sustained by athletes without diagnosed concussion. Accordingly, this analysis quantified repetitive head impact exposure in a cohort of 50 concussed NCAA Division I FBS college football athletes compared to controls that were matched for team and position group. The analysis quantified the number of head impacts and risk weighted exposure both on the day of injury and for the season to the date of injury. 43% of concussed athletes had the most severe head impact exposure on the day of injury compared to their matched control group and 46% of concussed athletes had the most severe head impact exposure for the season to the date of injury compared to their matched control group. When accounting for date of injury or season to date of injury, 72% of all concussed athletes had the most or second most severe head impact exposure compared to their matched control group. These trends associating cumulative head impact exposure with concussion onset were stronger for athletes that participated in a greater number of contact activities. For example, 77% of athletes that participated in ten or more days of contact activities had greater head impact exposure than their matched control group. This unique analysis provided further evidence for the role of repetitive head impact exposure as a predisposing factor for the onset of concussion. The clinical implication of these findings supports contemporary trends of limiting head impact exposure for college football athletes during practice activities in an effort to also reduce risk of concussive injury.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Repetitive head impacts in young athletes are potentially detrimental to later life (e.g., age 50 + years) neurological function; however, it is unknown what the short-term effects (e.g., age ...20 years) are in collegiate student-athletes.
The purpose of this study was to determine the effect of the estimated age of first exposure to American tackle football participation on neurocognitive performance and symptom severity scores in collegiate student-athletes.
We used a cohort study in which neurocognitive performance was assessed using the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) test in 4376 male athletes (age 19.3 ± 1.5 years, mass 96.3 ± 20.3 kg, height 185.0 ± 7.4 cm). Athletes were grouped by sport participation American football (n = 3462) or non-contact (n = 914) and estimated age of first exposure < 12 years (n = 3022) or ≥ 12 years (n = 1354). The outcome measures were the four primary cognitive scores and the symptom severity score from ImPACT. We assessed primary outcomes across groups, controlling for age, learning accommodations, and concussion history.
Neurocognitive performance was not associated with the estimated age of first exposure-by-group interaction.
Our findings indicate that participation in American tackle football before age 12 years does not result in neurocognitive deficits in college. Therefore, we suggest the following: the consequences of early exposure to repetitive head impacts do not manifest by college, the ImPACT test was not sensitive enough to identify the effects of an earlier estimated age of first exposure, or there is no association between an earlier estimated age of first exposure and neurocognitive functioning. Future longitudinal studies are warranted.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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