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Objective To evaluate pre - to post-season differences in individual subtests of the Visio-Vestibular Examination (VVE) in healthy middle and high school athletes. Methods This prospective cohort study recruited participants from a private suburban United States secondary school. Participants completed a demographic questionnaire prior to the start of their season. A proxy for head impact exposure was estimated by incorporating previously published head impact frequencies by team and sport. The VVE was completed pre - and post-season and consisted of 9 subtests: smooth pursuit, horizontal/vertical saccades and gaze stability, binocular convergence, left/right monocular accommodation, and complex tandem gait. Generalized estimating equations were employed to assess the relative risk of an abnormal VVE outcome based on testing session (pre - vs. post-season). Results Participants included middle and high school athletes (n = 115; female = 59 (51.3%); median age at first assessment = 14.9 years, [IQR = 13.6, 16.0]) during 2017/18 - 2019/20 school years. During pre-season testing, accommodation (10.0%) and complex tandem gait (9.2%) had the largest proportion of abnormal outcomes, while smooth pursuits (10.6%) and convergence (9.5%) had the largest proportion of abnormal outcomes post-season. When assessing the effect of testing session on the relative risk of any abnormal VVE subtest, there were no significant findings (P ≥ 0.25). Additionally, there were no significant effects of testing session when adjusting for estimated head impact exposure for any VVE subtest (P ≥ 0.25). Conclusions Visio-vestibular function as measured by the VVE does not change from pre - to post-season in otherwise healthy adolescent athletes. Our findings suggest that the VVE may be stable and robust to typical neurodevelopment occurring in this dynamic age group and help inform post-injury interpretation of visio-vestibular impairments.

Background Surgery causes transient impairment in cognition and function, which may impact driving safety. The authors hypothesized that the risk of a motor vehicle crash would increase after compared to before surgery. Methods The authors performed a nested case-crossover study within population-based observational data from the New Jersey Safety Health Outcomes Data Warehouse. The study included adults 18 yr or older with a valid driver’s license who underwent general surgery in an acute care hospital in New Jersey between January 1, 2016, and November 30, 2017, and were discharged home. Individuals served as their own controls within a presurgery interval (56 days to 28 days before surgery) and postsurgery interval (discharge through 28 days after surgery). General surgery was defined by Common Procedural Terminology Codes. The primary outcome was a police-reported motor vehicle crash. Results In a cohort of 70,722 drivers, the number of crashes after surgery was 263 (0.37%) compared to 279 (0.39%) before surgery. Surgery was not associated with a change in crash incidence greater than 28 days using a case-crossover design (adjusted incidence rate ratio, 0.92; 95% CI, 0.78 to 1.09; P = 0.340). Statistical interaction was present for sex and hospital length of stay. Younger versus older adults (adjusted risk ratio, 1.87; 95% CI, 1.10 to 3.18; P = 0.021) and non-Hispanic Black individuals (adjusted risk ratio, 1.96; 95% CI, 1.33 to 2.88; P = 0.001) and Hispanic individuals (adjusted risk ratio, 1.38; 95% CI, 1.00 to 1.91; P = 0.047) versus non-Hispanic White individuals had a greater risk of a crash after surgery. Conclusions Using population-based crash and hospital discharge data, the incidence of motor vehicle crashes over a 28-day period did not change on average before compared to after surgery. The authors provide data on crash risk after surgery and highlight specific populations at risk. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

In 30 states, licensing agencies can restrict the distance from home that "medically-at-risk" drivers are permitted to drive. However, where older drivers crash relative to their home or how distance to crash varies by medical condition is unknown. Using geocoded crash locations and residential addresses linked to Medicare claims, we describe how the relationship between distance from home to crash varies by driver characteristics. We find that a majority of crashes occur within a few miles from home with little variation across driver demographics or medical conditions. Thus, distance restrictions may not reduce crash rates among older adults, and the tradeoff between safety and mobility warrants consideration.

Adolescents with attention-deficit/hyperactivity disorder (ADHD) have 30%-40% higher crash rates. However, we still do not understand which factors underlie heightened crash risk and if crash circumstances differ for drivers with ADHD. We compared prevalences of crash responsibility, driver actions, and crash types among adolescent and young adult drivers with and without ADHD who crashed within 48 months of licensure.In this exploratory retrospective cohort study, we identified patients of Children's Hospital of Philadelphia's (CHOP) New Jersey (NJ) primary care locations who were born between 1987 and 2000, NJ residents, had their last CHOP visit ≥ age 12 years, and acquired a driver's license. We linked CHOP electronic health records to NJ's licensing and crash databases. ADHD diagnosis was based on International Classification of Diseases, Ninth Revision, Clinical Modification/International Classification of Diseases, Tenth Revision, Clinical Modification codes. Prevalence ratios were estimated using generalized estimating equation log-binomial regression.We identified 934 drivers with ADHD in 1,308 crashes and 5,158 drivers without ADHD in 6,676 crashes. Within 48 months postlicensure, drivers with ADHD were more likely to be at fault for their crash (prevalence ratio: 1.09 [1.05-1.14]) and noted as inattentive (1.15 [1.07-1.23]). With the exception that drivers with ADHD were less likely to crash while making a left/U-turn, we did not find substantial differences in crash types by diagnosis. Analyses also suggest females with ADHD may have a higher risk of colliding with a nonmotor vehicle and crashing due to unsafe speed than females without ADHD.The results suggest crash circumstances do not widely differ for drivers with and without ADHD but highlight several factors that may be particularly challenging for young drivers with ADHD.

Eye tracking assessments that include pupil metrics can supplement current clinical assessments of vision and autonomic dysfunction in concussed adolescents.This study aimed to explore the utility of a 220-second eye tracking assessment in distinguishing eye position, saccadic movement, and pupillary dynamics among uninjured adolescents, those with acute post-concussion symptoms (≤28 days since concussion), or those with persistent post-concussion symptoms (28 days since concussion).Two hundred fifty-six eye tracking metrics across a prospective observational cohort of 180 uninjured adolescents recruited from a private suburban high school and 224 concussed adolescents, with acute or persistent symptoms, recruited from a tertiary care subspecialty concussion care program, 13 to 17 years old, from August 2017 to June 2021 were compared. Kruskal-Wallis tests were used, and Bonferroni corrections were applied to account for multiple comparisons and constructed receiver operating characteristic curves. Principal components analysis and regression models were applied to determine whether eye tracking metrics can augment clinical and demographic information in differentiating uninjured controls from concussed adolescents.Two metrics of eye position were worse in those with concussion than uninjured adolescents, and only one metric was significantly different between acute cases and persistent cases. Concussed adolescents had larger left and right mean, median, minimum, and maximum pupil size than uninjured controls. Concussed adolescents had greater differences in mean, median, and variance of left and right pupil size. Twelve metrics distinguished female concussed participants from uninjured; only four were associated with concussion status in males. A logistic regression model including clinical and demographics data and transformed eye tracking metrics performed better in predicting concussion status than clinical and demographics data alone.Objective eye tracking technology is capable of quickly identifying vision and pupillary disturbances after concussion, augmenting traditional clinical concussion assessments. These metrics may add to existing clinical practice for monitoring recovery in a heterogeneous adolescent concussion population.

OBJECTIVE: The availability of complete and accurate crash injury data is critical to prevention and intervention efforts. Relying solely on hospital discharge data or police crash reports may result in a biased undercount of injuries. Linking hospital data with crash reports may allow for a more robust identification of injuries and an understanding of which populations may be missed in an analysis of one source. We used the New Jersey Safety and Health Outcomes (NJ-SHO) data warehouse to examine the share of the entire crash-injured population identified in each of the two data sources, overall and by age, race/ethnicity, sex, injury severity, and road user type. METHODS: We utilized 2016-2017 data from the NJ-SHO warehouse. We identified crash-involved individuals in hospital discharge data by applying the ICD-10-CM external cause of injury matrix. Among crash-involved individuals, we identified those with injury- or pain-related diagnosis codes as being injured. We also identified crash-involved individuals via crash report data and identified injuries using the KABCO scale. We jointly examined the two sources; injuries in the hospital discharge data were documented as being related to the same crash as injuries found in the crash report data if the date of the crash report preceded the date of hospital admission by no more than two days. RESULTS: In total, there were 262,338 crash-involved individuals with a documented injury in the hospital discharge data or on the crash report during the study period; 168,874 had an injury according to hospital discharge data, and 164,158 had an injury in crash report data. Only 70,694 (26.9%) had an injury in both sources. We observed differences by age, race/ethnicity, injury severity, and road user type: hospital discharge data captured a larger share of those ages 65+, those who were Black or Hispanic, those with higher severity injuries, and those who were bicyclists or motorcyclists. CONCLUSIONS: Each data source in isolation captures approximately two-thirds of the entire crash-injured population; one source alone misses approximately one-third of injured individuals. Each source undercounts people in certain groups, so relying on one source alone may not allow for tailored prevention and intervention efforts.

RATIONALE: Recreational and medical use of stimulants is increasing, and their use may increase susceptibility to aging and promote neurobehavioral impairments. The long-term consequences of these psychostimulants and how they interact with age have not been fully studied. OBJECTIVES: Our study investigated whether chronic exposure to the prototypical psychostimulant, methamphetamine (METH), at doses designed to emulate human therapeutic dosing, would confer a pro-oxidizing redox shift promoting long-lasting neurobehavioral impairments. METHODS: Groups of 4-month-old male and female C57BL/6J mice were administered non-contingent intraperitoneal injections of either saline or METH (1.4 mg/kg) twice a day for 4 weeks. Mice were randomly assigned to one experimental group: (i) short-term cognitive assessments (at 5 months), (ii) long-term cognitive assessments (at 9.5 months), and (ii) longitudinal motor assessments (at 5, 7 and 9 months). Brain regions were assessed for oxidative stress and markers of neurotoxicity after behavior testing. RESULTS: Chronic METH exposure induced short-term effects on associative memory, gait speed, dopamine (DA) signaling, astrogliosis in females and spatial learning and memory, balance, DA signaling, and excitotoxicity in males. There were no long-term effects of chronic METH on cognition, however, it decreased markers of excitotoxicity in the striatum and exacerbated age-associated motor impairments in males. CONCLUSION: In conclusion, cognitive and motor function were differentially and sex-dependently affected by METH exposure, and oxidative stress did not seem to play a role in the observed behavioral outcomes. Future studies are necessary to continue exploring the long-term neurobehavioral consequences of drug use in both sexes and the relationship between aging and drugs.

OBJECTIVE: To characterize healthcare and behavioral service providers’ transportation-related discussions with their autistic and non-autistic patients. METHOD: 78 providers completed a cross-sectional survey assessing their transportation discussions with patients. We used Mann–Whitney U tests and chi-square tests to compare differences in provider reports by patient diagnosis. RESULTS: Compared with one in two providers who reported they discuss transportation with non-autistic patients, only one in five have these conversations with their autistic patients. Few (8%) providers felt prepared to assess driving readiness in autistic patients, yet only a quarter refer patients elsewhere. CONCLUSION: There is a critical need to develop resources for use in medical settings to effectively support autistic adolescents’ independence and mobility as they transition into adulthood.

We investigate the transient dynamics of a sheared suspension of neutrally buoyant particles under pressure-imposed conditions, subject to a sudden change in shear rate or external pressure. Discrete Element Method simulations show that, depending on the flow parameters (particle and system size, initial volume fraction), the early stress response of the suspension may strongly differ from the prediction of the Suspension Balance Model based on the steady-state rheology. We show that a two-phase model incorporating the Reynolds-like dilatancy law of Pailha & Pouliquen (2009), which prescribes the dilation rate of the suspension over a strain scale $\gamma_0$, quantitatively captures the suspension dilation/compaction over the whole range of parameters investigated. Together with the Darcy flow induced by the pore pressure gradient during dilation or compaction, this Reynolds-like dilatancy implies that the early stress response of the suspension is nonlocal, with a nonlocal length scale $\ell$ which scales with the particle size and diverges algebraically at jamming. In regions affected by $\ell$, the stress level is fixed, not by the steady-state rheology, but by the Darcy fluid pressure gradient resulting from the dilation/compaction rate. Our results extend the validity of the Reynolds-like dilatancy flow rule, initially proposed for jammed suspensions, to flowing suspension below $\phi_\mathrm{c}$, thereby providing a unified framework to describe dilation and shear-induced migration. They pave the way for understanding more complex unsteady flows of dense suspensions, such as impacts, transient avalanches or the impulsive response of shear-thickening suspensions., Comment: 24 pages, 9 figures

Background: Few studies have examined psychiatric symptoms during the acute phase following a concussion in adolescents. Thus, this study compares anxiety and depression in acutely concussed and nonconcussed adolescents. Hypothesis: Acutely concussed adolescents will report greater anxiety and depressive symptoms compared with nonconcussed adolescents. Study Design: Prospective cohort study. Level of Evidence: Level 3. Methods: Data were collected from 282 adolescents (111 concussed within 28 days of injury, 171 nonconcussed), 13 to 18 years of age, who completed Patient-Reported Outcome Measurement Information System (PROMIS) Anxiety and Depressive Symptoms measures. We calculated average T-scores for anxiety and depression across both groups and compared the proportion of those who scored above normal limits. Finally, we calculated risk ratios for anxiety and depression scores above normal limits. Results: Average T-scores for anxiety did not differ in concussed versus nonconcussed adolescents (mean: 45.9 [SD 10.84] vs 45.2 [8.1], respectively, P = 0.54), whereas average T-scores for depression were significantly higher in concussed versus nonconcussed adolescents (46.0 [10.88] vs 42.8 [8.48], respectively, P < 0.01). The proportion of concussed adolescents above normal limits for depression was greater than nonconcussed adolescents (32.4% vs 20.5%, respectively, P = 0.02). Post hoc sensitivity analyses excluding those with a history of anxiety or depression demonstrated a 1.45 (95% CI, 0.97, 2.01) and 1.56 (95% CI, 0.95, 2.56) increased risk of an above-normal anxiety and depression score for concussed compared with nonconcussed adolescents, respectively, although both were nonsignificant. Conclusion: Although we found few significant differences between the 2 groups, the results highlight that many concussed adolescents met the threshold for above-average symptoms on the depression and anxiety PROMIS measures. Clinical Relevance: In adolescents, there is increased risk for psychiatric sequalae in the acute period after a concussion. As such, we suggest that clinicians consider incorporating depression screening when caring for adolescents after a concussion.

OBJECTIVE: National data suggest drivers who are younger, older, and have lower socioeconomic status (SES) have heightened crash-related injury rates. Ensuring vulnerable drivers are in the safest vehicles they can afford is a promising approach to reducing crash injuries in these groups. However, we do not know the extent to which these drivers are disproportionately driving less safe vehicles. Our objective was to obtain population-based estimates of the prevalence of important vehicle safety criteria among a statewide population of drivers. METHODS: We analyzed data from the NJ Safety and Health Outcomes warehouse, which includes all licensing and crash data from 2010–2017. We borrowed the quasi-induced exposure method’s fundamental assumption—that non-responsible drivers in clean (i.e., only one responsible driver) multi-vehicle crashes are reasonably representative of drivers on the road—to estimate statewide prevalence of drivers’ vehicle characteristics across four driver age groups (17–20; 21–24; 25–64, and ≥65) and quintiles of census tract median household income (n=983,372). We used NHTSA’s Product Information Catalog and Vehicle Listing platform (vPIC) to decode the VIN of each crash-involved vehicle to obtain model year, presence of electronic stability control (ESC), vehicle type, engine horsepower, and presence of front, side, and curtain air bags. RESULTS: The youngest and oldest drivers were more likely than middle-aged drivers to drive vehicles that were older, did not have ESC, and were not equipped with side airbags. Additionally, across all age groups drivers of higher SES were in newer and safer vehicles compared with those of lower SES. For example, young drivers living in lowest-income census tracts drove vehicles that were on average almost twice as old as young drivers living in highest-income tracts (median [IQR]: 11 years [6–14] vs. 6 years [3–11]). CONCLUSIONS: Vehicle safety is an important component of seminal road safety philosophies that aim to reduce crash fatalities. However, driver groups that are overrepresented in fatal crashes--young drivers, older drivers, and those of lower SES—are also driving the less safe vehicles. Ensuring drivers are in the safest car they can afford should be further explored as an approach to reduce crash-related injuries among vulnerable populations.

Background: While concussions are common pediatric injuries, a lack of agreement on a standard definition of recovery creates multiple challenges for clinicians and researchers alike. Hypothesis: The percentage of concussed youth deemed recovered as part of a prospective cohort study will differ depending on the recovery definition. Study Design: Descriptive epidemiologic study of a prospectively enrolled observational cohort Level of Evidence: Level 3. Methods: Participants aged 11 to 18 years were enrolled from the concussion program of a tertiary care academic center. Data were collected from initial and follow-up clinical visits ≤12 weeks from injury. A total of 10 recovery definitions were assessed: (1) cleared to full return to sports; (2) return to full school; (3) self-reported return to normal; (4) self-reported full return to school; (5) self-reported full return to exercise; (6) symptom return to preinjury state; (7) complete symptom resolution; (8) symptoms below standardized threshold; (9) no abnormal visio-vestibular examination (VVE) elements; and (10) ≤1 abnormal VVE assessments. Results: In total, 174 participants were enrolled. By week 4, 63.8% met at least 1 recovery definition versus 78.2% by week 8 versus 88.5% by week 12. For individual measures of recovery at week 4, percent recovered ranged from 5% by self-reported full return to exercise to 45% for ≤1 VVE abnormality (similar trends at 8 and 12 weeks). Conclusion: There is wide variability in the proportion of youth considered recovered at various points following concussion depending on the definition of recovery, with higher proportions using physiologic examination-based measures and lower proportions using patient-reported measures. Clinical Relevance: These results further emphasize the need for a multimodal assessment of recovery by clinicians as a single and standardized definition of recovery that captures the broad impact of concussion on a given patient continues to be elusive.

The interplay between chemical reaction and substrate deformation is discussed by adapting Ranz's formulation for scalar mixing to the case of a reactive mixture between segregated reactants, initially separated by an interface whose thickness may not be vanishingly small. Experiments in a simple shear flow demonstrate the existence of three regimes depending on the Damköhler number $Da=t_s/t_c$ where $t_s$ is the mixing time of the interface width and $t_c$ is the chemical time. Instead of treating explicitly the chemical cross-term, we rationalize these different regimes by globalizing it as a production term involving a flux which depends on the rate at which the reaction zone is fed by the reactants, a formulation valid for $Da>1$. For $Da, the reactants interpenetrate before they react, giving rise to a ‘diffusio-chemical’ regime where chemical production occurs within a substrate whose width is controlled by molecular diffusion.

We present late-time radio/millimeter (as well as optical/UV and X-ray) detections of the tidal disruption event (TDE) AT2018hyz, spanning $970 - 1300$ d after optical discovery. In conjunction with earlier deeper limits, including at $\approx 700$ d, our observations reveal rapidly rising emission at $0.8-240$ GHz, steeper than $F_\nu\propto t^5$ relative to the time of optical discovery. Such a steep rise cannot be explained in any reasonable scenario of an outflow launched at the time of disruption (e.g., off-axis jet, sudden increase in the ambient density), and instead points to a delayed launch. Our multi-frequency data allow us to directly determine the radius and energy of the radio-emitting outflow, showing that it was launched $\approx 750$ d after optical discovery. The outflow velocity is mildly relativistic, with $\beta\approx 0.25$ and $\approx 0.6$ for a spherical and a $10^\circ$ jet geometry, respectively, and the minimum kinetic energy is $E_K\approx 5.8\times 10^{49}$ and $\approx 6.3\times 10^{49}$ erg, respectively. This is the first definitive evidence for the production of a delayed mildly-relativistic outflow in a TDE; a comparison to the recently-published radio light curve of ASASSN-15oi suggests that the final re-brightening observed in that event (at a single frequency and time) may be due to a similar outflow with a comparable velocity and energy. Finally, we note that the energy and velocity of the delayed outflow in AT2018hyz are intermediate between those of past non-relativistic TDEs (e.g., ASASSN-14li, AT2019dsg) and the relativistic TDE Sw\,J1644+57. We suggest that such delayed outflows may be common in TDEs., Comment: Submitted to ApJ

To assess if abnormalities on visio-vestibular examination (VVE) are associated with concussion history (first vs. repeat) or age of first concussion in acutely concussed adolescents.Cross-sectional.Data were queried from the Children's Hospital of Philadelphia Minds Matter concussion registry. Patients aged 14-18 years old presenting for their initial visit to the specialty care concussion program within 28 days of injury were included. Demographics, including age, sex, concussion history, and age of first concussion, were collected before the exam. The VVE consisted of 9 subtests: smooth pursuit, horizontal/vertical saccades and vestibulo-ocular reflex (VOR), binocular convergence, left/right monocular accommodation, and complex tandem gait. Primary outcomes included VVE subtests (normal/abnormal), and total VVE score (abnormal = 2+ abnormal subtests).Among 1051 patients included (female = 604(57.5 %); age = 15.6 ± 1.2; median lifetime concussions = 1 [IQR = 1,3]), 518 had repeat concussion. Controlling for age and sex, first vs. repeat concussion was not associated with any VVE subtest or total score (Total VVE Score RR = 1.35, 99.5%CI = 0.70,2.61). Of those with repeat concussion, 190 had valid age of first concussion data. Controlling for age, sex, and number of lifetime concussions, age of first concussion was not significantly associated with any VVE subtest or total score (Total VVE Score RR = 1.11, 99.5%CI = 0.78,1.57).Adolescents with concussion history present with similar visio-vestibular function to those with no concussion history. Additionally, clinical effects of early age of first concussion may not be evident in children. This study provides foundational data regarding potential cumulative effects of concussion in younger athletes.

Background/ObjectivesThirty states allow licensing agencies to restrict the distance from home that “medically-at-risk” drivers are permitted to drive. However, there is little information on where older drivers crash relative to their home or how distance to crash varies by medical condition, and thus, what impact distance limits may have on motor vehicle crash rates for “medically-at-risk” drivers.DesignObservational study of crash-involved drivers.SettingMedicare fee-for-service claims linked to geocoded crash locations and residential addresses from police crash reports in the state of New Jersey from 2007 through 2017.ParticipantsNew Jersey Medicare fee-for-service beneficiaries aged 68 years and older involved in police-reported crashes.MeasurementsThe outcome was Euclidian distance from home to crash location. Covariates included driving-relevant medical conditions from Medicare claims, crash characteristics from police reports, and demographics from both sources.ResultsThere were 197,122 crash-involved older drivers for whom approximately 70% of crashes occurred within 5 miles and 95% within 25 miles of the driver’s residence. The mean distance to crash was 6.0 miles. Although distance from home to the crash was generally lower among drivers with (versus without) each of the medical conditions studied, the differences were small (maximum mean difference of 2.1 miles). The largest difference in distance was by licensure status, where unlicensed/suspended drivers crashed significantly farther from home than validly licensed drivers (8.8 miles, 95% Confidence Interval [CI]: 8.4-9.1 vs 5.9 miles, 95% CI: 5.9 – 6.0).ConclusionsFindings suggest that the majority of older adults who crash do so within a few miles from home and that the distance to crash does not differ substantially by the presence of a driving-relevant medical condition. Thus, distance restrictions may not reduce crash rates among older adults and the tradeoff between safety and mobility warrants consideration.KEYPOINTS30 states permit restriction of driving distance for medically-at-risk driversThe vast majority of crashes involving older drivers occur ≤ 25 miles of homeDistance to crash does not differ markedly across driving-relevant medical conditionsWhy does this matter?Distance restrictions are likely to impact mobility and autonomy but not crash rates

Increasing age disproportionately increases the risk of stroke among women compared to men of similar age, especially after menopause. One of the reasons for this observation is a sharp drop in circulating estrogens. However, the timing of initiation of estrogen replacement after menopause is associated with mixed beneficial and detrimental effects, hence contributing to widespread mistrust of estrogen use. Agents including soy isoflavones are being assessed as viable alternatives to estrogen therapy. In this study, we hypothesized that the neuroprotective effects of genistein, a soy isoflavone are less sensitive to the length of hypogonadism in young adult ovariectomized rats following cerebral ischemia. We expected that long-term hypogonadism will worsen motor and cognitive function, increase post-stroke inflammation with no effect on the neuroprotection of genistein. We compared the effect of treatment with dietary genistein (GEN) on short-term (2 weeks) and long-term hypogonadism (12 weeks) in young adult ovariectomized Sprague-Dawley rats on sensorimotor function, cognition and inflammation after focal ischemia. Dorsal Silastic implant of 17β-estradiol (E2) was used as a control for hormone therapy. Long-term hypogonadism stroked rats performed worse than the short-term hypogonadism stroked rats on the motor and cognitive function tests. GEN did not improve neurological assessment and motor learning after either short-term or long-term hypogonadism. GEN improved cognitive flexibility after short-term hypogonadism but not after the long-term. Both GEN and E2 reduced tissue loss after short-term hypogonadism and reduced GFAP expression at the contralateral side of ischemia after long-term hypogonadism. The length of hypogonadism may differentially influence the neuroprotective effects of both GEN and E2 on the motor and cognitive functions in young adult rats.

Introduction Driving is important for well-being among older adults, but age-related conditions are associated with driving reduction or cessation and increased crash risk for older drivers. Our objectives were to describe population-based rates of older drivers’ licensing and per-driver rates of crashes and moving violations. Methods: We examined individual-level statewide driver licensing, crash, and traffic citation data among all New Jersey drivers aged ≥ 65 and a 35- to 54-year-old comparison group during 2010–2014. Rate ratios (RR) of crashes and moving violations were estimated using Poisson regression. Results: Overall, 86% of males and 71% of females aged ≥ 65 held a valid driver’s license. Older drivers had 27% lower per-driver crash rates than middle-aged drivers (RR: 0.73, 95% CI: 0.73, 0.74)—with appreciable differences by sex—but 40% higher fatal crash rates (RR: 1.40 [1.24, 1.58]). Moving violation rates among older drivers were 72% lower than middle-aged drivers (RR: 0.28 [0.28, 0.28]). Conclusion: The majority of older adults are licensed, with substantial variation by age and sex. Older drivers have higher rates of fatal crashes but lower rates of moving violations compared with middle-aged drivers. Practical applications: Future research is needed to understand the extent to which older adults drive and to identify opportunities to further reduce risk of crashes and resultant injuries among older adults.

Objectives The objectives are to (1) describe disability outcomes at 24 months after injury and (2) identify factors contributing to disability outcomes at 24 months after injury, for Māori and non-Māori who have been hospitalised for injury. Study design This is a prospective cohort study. Methods Prospective Outcomes of Injury Study participants were injured New Zealanders aged 18–64 years and recruited from New Zealand's no-fault injury insurer, the Accident Compensation Corporation's entitlement claims register. Data about a number of pre-injury, injury-related and early post-injury characteristics were collected from interviews held at 3 and 24 months after injury. Disability was measured using the World Health Organization Disability Assessment Schedule (WHODAS). Modified Poisson regression modelling was used to estimate relative risks (RRs) of disability for Māori and non-Māori who were hospitalised for injury. Results Analyses were restricted to 375 Māori and 1824 non-Māori participants for whom complete data were available. Of these, 105 (28%) Māori and 446 (24%) non-Māori were hospitalised for their injury. Of these hospitalised groups, 26% of Māori and 10% of non-Māori were experiencing disability (WHODAS ≥10) at 24 months after injury. Māori who were hospitalised for injury and who were not working for pay before their injury (RR = 2.7; 95% confidence interval [CI] 1.4–4.9), who were experiencing disability before their injury (RR = 3.1; 95% CI 1.6–5.8) or who reported trouble accessing healthcare services for their injury (RR = 2.6; 95% CI 1.3–5.2) were independently at increased risk of disability 24 months after injury. Non-Māori who were hospitalised for injury and who had inadequate household income before injury (RR = 2.4; 95% CI 1.4–4.1), less than the secondary school qualifications (RR = 2.0; 95% CI 1.1–3.8), were not working for pay before injury (RR = 2.8; 95% CI 1.5–5.1), were experiencing disability before their injury (RR = 3.0; 95% CI 1.7–5.2), had ≥2 chronic conditions (RR = 3.5; 95% CI 2.0–6.4) or had body mass index ≥30 kg/m2/undisclosed (RR = 2.4; 95% CI 1.3–4.4) were at increased risk of disability 24 months after injury. Conclusions Variables predicting disability 24 months after injury for Māori, also predict disability 24 months after injury for non-Māori, with one notable exception—trouble accessing healthcare services. Our findings show that having access to healthcare services for injury plays an important role after injury and must be focussed on to ensure that the burden of poor injury-related outcomes and injury-related inequities are reduced and ultimately eliminated.

A 1.7 Å resolution co-crystal structure of U7BR from Schizosaccharomyces pombe in complex with Ubc7 is reported. Structural comparisons and biochemistry suggest that U7BR presents a steric impediment to E1 binding and inhibits E1-mediated charging, respectively., Endoplasmic reticulum (ER)-associated degradation (ERAD) is a protein quality-control pathway in eukaryotes in which misfolded ER proteins are polyubiquitylated, extracted and ultimately degraded by the proteasome. This process involves ER membrane-embedded ubiquitin E2 and E3 enzymes, as well as a soluble E2 enzyme (Ubc7 in Saccharomyces cerevisiae and UBE2G2 in mammals). E2-binding regions (E2BRs) that recruit these soluble ERAD E2s to the ER have been identified in humans and S. cerevisiae, and structures of E2–E2BR complexes from both species have been determined. In addition to sequence and structural differences between the human and S. cerevisiae E2BRs, the binding of E2BRs also elicits different biochemical outcomes with respect to E2 charging by E1 and E2 discharge. Here, the Schizosaccharomyces pombe E2BR was identified and purified with Ubc7 to resolve a 1.7 Å resolution co-crystal structure of the E2BR in complex with Ubc7. The S. pombe E2BR binds to the back side of the E2 as an α-helix and, while differences exist, it exhibits greater similarity to the human E2BR. Structure-based sequence alignments reveal differences and conserved elements among these species. Structural comparisons and biochemistry reveal that the S. pombe E2BR presents a steric impediment to E1 binding and inhibits E1-mediated charging, respectively.

In mouse models of Alzheimer's disease (AD), normobaric intermittent hypoxia training (IHT) can preserve neurobehavioral function when applied before deficits develop, but IHT's effectiveness after onset of amyloid-β (Aβ) accumulation is unclear. This study tested the hypothesis that IHT improves learning-memory behavior, diminishes Aβ accumulation in cerebral cortex and hippocampus, and enhances cerebrocortical contents of the neuroprotective trophic factors erythropoietin and brain-derived neurotrophic factor (BDNF) in mice manifesting AD traits. Twelve-month-old female 3xTg-AD mice were assigned to untreated 3xTg-AD (n = 6), AD+IHT (n = 6), and AD+sham-IHT (n = 6) groups; 8 untreated wild-type (WT) mice also were studied. AD+IHT mice alternately breathed 10% O2 for 6 min and room air for 4 min, 10 cycles/day for 21 days; AD+sham-IHT mice breathed room air. Spatial learning-memory was assessed by Morris water maze. Cerebrocortical and hippocampal Aβ40 and Aβ42 contents were determined by ELISA, and cerebrocortical erythropoietin and BDNF were analyzed by immunoblotting and ELISA. The significance of time (12 vs. 12 months + 21 days) and treatment (IHT vs. sham-IHT) was evaluated by two-factor ANOVA. The change in swimming distance to find the water maze platform after 21 d IHT (−1.6 ± 1.8 m) differed from that after sham-IHT (+5.8 ± 2.6 m). Cerebrocortical and hippocampal Aβ42 contents were greater in 3xTg-AD than WT mice, but neither time nor treatment significantly affected Aβ40 or Aβ42 contents in the 3xTg-AD mice. Cerebrocortical erythropoietin and BDNF contents increased appreciably after IHT as compared to untreated 3xTg-AD and AD+sham-IHT mice. In conclusion, moderate, normobaric IHT prevented spatial learning-memory decline and restored cerebrocortical erythropoietin and BDNF contents despite ongoing Aβ accumulation in 3xTg-AD mice.

Objective: To characterize healthcare and behavioral service providers’ transportation-related discussions with their autistic and non-autistic patients.Method: Seventy-eight providers completed a cross-sectional survey assessing their transportation discussions with patients. We used Mann-Whitney U tests and chi-square tests to compare differences in provider reports by patient diagnosis.Results: Compared with one in two providers who reported they discuss transportation with non-autistic patients, only one in five have these conversations with their autistic patients. Few (8%) providers felt prepared to assess driving readiness in autistic patients, yet only a quarter refer patients elsewhere.Conclusion: There is a critical need to develop resources for use in medical settings to effectively support autistic adolescents’ independence and mobility as they transition into adulthood.

Objective One-third of autistic individuals obtain a driver’s license by age 21 years; however, prior studies suggest they may be at heightened risk for motor vehicle crashes. We compared objective rates of crashes, traffic violations, and license suspensions for newly licensed autistic and non-autistic adolescents. Method This retrospective cohort study included New Jersey residents born from 1987 through 2000 who were patients of the Children’s Hospital of Philadelphia health care network. Electronic health records were linked with statewide driver licensing and crash databases. Autism status was classified via International Classification of Diseases (ICD) diagnostic codes; individuals with intellectual disability were excluded. We compared rates among 486 autistic and 70,990 non-autistic licensed drivers over their first 48 months of driving. Furthermore, we examined the proportion of crashes attributed to specific driver actions and crash types. Results Compared with non-autistic drivers, autistic drivers were estimated to have lower average monthly rates of crash involvement (adjusted rate ratio (adjRR) = 0.89, 95% CI = 0.75–1.05), moving violations (adjRR = 0.56, 95% CI = 0.48–0.67), and suspensions (adjRR = 0.32, 95% CI = 0.18–0.58). Among drivers involved in a crash, autistic drivers were half as likely to crash because of unsafe speed, but substantially more likely to crash because of their failure to yield to a vehicle/pedestrian and while making left-turns or U-turns. Conclusion Newly licensed autistic adolescent drivers have similar to lower estimated rates of adverse driving outcomes; the extent to which these can be attributed to different driving patterns is a critical point for future investigation. There were several notable differences in the characteristics of these crashes, which directly inform interventions to improve driving safety of autistic adolescent drivers.

ObjectiveOur objective was to describe the development of the New Jersey Safety and Health Outcomes (NJ-SHO) data warehouse—a unique and comprehensive data source that integrates state-wide administrative databases in NJ to enable the field of injury prevention to address critical, high-priority research questions.MethodsWe undertook an iterative process to link data from six state-wide administrative databases from NJ for the period of 2004 through 2018: (1) driver licensing histories, (2) traffic-related citations and suspensions, (3) police-reported crashes, (4) birth certificates, (5) death certificates and (6) hospital discharges (emergency department, inpatient and outpatient). We also linked to electronic health records of all NJ patients of the Children’s Hospital of Philadelphia network, census tract-level indicators (using geocoded residential addresses) and state-wide Medicaid/Medicare data. We used several metrics to evaluate the quality of the linkage process.ResultsAfter the linkage process was complete, the NJ-SHO data warehouse included linked records for 22.3 million distinct individuals. Our evaluation of this linkage suggests that the linkage was of high quality: (1) the median match probability—or likelihood of a match being true—among all accepted pairs was 0.9999 (IQR: 0.9999–1.0000); and (2) the false match rate—or proportion of accepted pairs that were false matches—was 0.0063.ConclusionsThe resulting NJ-SHO warehouse is one of the most comprehensive and rich longitudinal sources of injury data to date. The warehouse has already been used to support numerous studies and is primed to support a host of rigorous studies in the field of injury prevention.

Importance Concussion diagnosis remains clinical, without objective diagnostic tests available for adolescents. Known deficits in visual accommodation and autonomic function after concussion make the pupillary light reflex (PLR) a promising target as an objective physiological biomarker for concussion. Objective To determine the potential utility of PLR metrics as physiological biomarkers for concussion. Design, Setting, and Participants Prospective cohort of adolescent athletes between ages 12 and 18 years recruited between August 1, 2017, and December 31, 2018. The study took place at a specialty concussion program and private suburban high school and included healthy control individuals (n = 134) and athletes with a diagnosis of sport-related concussion (SRC) (n = 98). Analysis was completed June 30, 2020. Exposures Sports-related concussion and pupillometry assessments. Main Outcomes and Measures Pupillary light reflex metrics (maximum and minimum pupillary diameter, peak and average constriction/dilation velocity, percentage constriction, and time to 75% pupillary redilation [T75]). Results Pupillary light reflex metrics of 134 healthy control individuals and 98 athletes with concussion were obtained a median of 12.0 days following injury (interquartile range [IQR], 5.0-18.0 days). Eight of 9 metrics were significantly greater among athletes with concussion after Bonferroni correction (maximum pupil diameter: 4.83 mm vs 4.01 mm; difference, 0.82; 99.44% CI, 0.53-1.11; minimum pupil diameter: 2.96 mm vs 2.63 mm; difference, 0.33; 99.4% CI, 0.18-0.48; percentage constriction: 38.23% vs 33.66%; difference, 4.57; 99.4% CI, 2.60-6.55; average constriction velocity: 3.08 mm/s vs 2.50 mm/s; difference, 0.58; 99.4% CI, 0.36-0.81; peak constriction velocity: 4.88 mm/s vs 3.91 mm/s; difference, 0.97; 99.4% CI, 0.63-1.31; average dilation velocity, 1.32 mm/s vs 1.22 mm/s; difference, 0.10; 99.4% CI, 0.00-0.20; peak dilation velocity: 1.83 mm/s vs 1.64 mm/s; difference, 0.19; 99.4% CI, 0.07-0.32; and T75: 1.81 seconds vs 1.51 seconds; difference, 0.30; 0.10-0.51). In exploratory analyses, sex-based differences were observed, with girls with concussion exhibiting longer T75 (1.96 seconds vs 1.63 seconds; difference, 0.33; 99.4% CI, 0.02-0.65). Among healthy control individuals, diminished PLR metrics (eg, smaller maximum pupil size 3.81 mm vs 4.22 mm; difference, −0.41; 99.4% CI, −0.77 to 0.05) were observed after exercise. Conclusions and Relevance These findings suggest that enhancement of PLR metrics characterize acute adolescent concussion, while exercise produced smaller pupil sizes and overall slowing of PLR metrics, presumably associated with fatigue. Quantifiable measures of the PLR may serve in the future as objective physiologic biomarkers for concussion in the adolescent athlete.

Objective The aim of the study was to comprehensively describe the natural history of concussion in early childhood between 0 and 4 years. Methods Retrospective cohort study of 329 patients aged 0 to 4 years, with an International Classification of Diseases, Ninth Revision, concussion diagnosis in the Children's Hospital of Philadelphia healthcare network from October 1, 2013, to September 30, 2015. Clinical data were abstracted from the Children's Hospital of Philadelphia electronic health record, which captured all clinical care visits and injury characteristics. Results Nearly 9 (86.6%) of 10 patients sought care in the emergency department or urgent care setting, most commonly on the day of injury (56.2%) and as a result of a fall (64.4%). More than two-thirds (64.4%) of patients or their parent/caregiver reported somatic symptoms (ie, vomiting or headache), whereas close to half (49.2%) reported sleep issues. One of 5 patients identified emotional symptoms (21.9%) or visio-vestibular dysfunction (20.4%). Many patients also experienced symptoms not included in standard assessment tools including personality changes (34.0%) and change in appetite (12.8%). Conclusions These results provide insight into the clinical characteristics of concussion in early childhood up to 4 years of age. Because assessment in this group relies heavily on parent/caregiver symptom reporting, rather than patient self-report, these results will aid clinicians with the challenge of diagnosing concussions in this population. These findings highlight the need to develop additional tools to adequately and systematically assess common signs and symptoms of concussion in early childhood that may not be included in standard assessment scales routinely used in older adolescents and adults.

To evaluate the discriminatory ability of different repetition increments of saccades and gaze stability testing for diagnosing concussion in adolescents.Cross-sectional.Suburban high school and academic pediatric tertiary care center.Sixty-nine adolescent athletes within 28 days of a sports- or recreation-related concussion and 69 adolescent athletes without recent concussion.Symptom provocation with horizontal and vertical saccades and gaze stability testing performed up to 30 repetitions.Sensitivity and specificity at 10-repetition increments (≤10, ≤20, ≤30) and area under the receiver operating characteristic curves (AUC) of a visio-vestibular examination (VVE) subscore, scored 0 to 4 based on the number of assessments with symptom provocation, at each repetition increment.Sensitivity improved when increasing from ≤10 to ≤20 to ≤30 repetitions for horizontal (25% to 50% to 69%) and vertical (32% to 52% to 74%) saccades and horizontal (19% to 45% to 71%) and vertical (23% to 45% to 72%) gaze stability. Specificity was comparable at ≤10 and ≤20 repetitions, but decreased at ≤30 repetitions across assessments. For a VVE subscore (0-4) based on the number of symptomatic assessments, the discriminatory ability of the test was highest at ≤20 repetitions (AUC of 0.79) with an optimal subscore of one (sensitivity 59%, specificity 96%).A VVE including a higher threshold level of repetitions for saccades and gaze stability has improved discriminatory ability for concussion, with an optimized AUC of 0.79 at ≤20 repetitions.The findings in this study suggest that a higher threshold level of repetitions of 2 commonly used visio-vestibular assessments enables clinicians to more accurately diagnose youth concussion.

Objective To comprehensively characterize the clinical presentation and course of care for concussion among 5- to 11-year-old children, identifying preinjury and injury factors potentially influencing clinical outcomes. Study design A single-institution retrospective cohort study using electronic health record data from children ages 5- to 11 years with a concussion from July 1, 2014, through June 30, 2015. Electronic health record data were abstracted for a 20% random sample of 292 patients. Results Three-fourths of patients (74.3%) presenting for concussion care had a standardized visiovestibular assessment performed. Almost all of those who eventually sought specialty care (92.9%) also had such an assessment, and only 42.9% patients initially seen in the emergency department or urgent care were examined in this manner. Of those assessed, 62.7% (n = 136) demonstrated deficits, with children ages 9-11 years more frequently exhibiting deficits than their younger counterparts (67.9% vs 53.2%; P = .03). Almost all patients (95.9%) reported at least 1 somatic symptom (eg, headache, dizziness), and one-half to two-thirds reported problems with sleep (54.1%) and visiovestibular symptoms (66.1%). Only 11.6% of children were referred for rehabilitation therapies and less than one-half of concussed patients (43.8%) were provided with a letter recommending school accommodations. Conclusions Somatic symptoms, sleep problems, and visiovestibular deficits are common in elementary school-aged children with concussion, but specific visiovestibular clinical assessments are often not performed, particularly in the emergency department setting. Recommendations for school accommodations are often not provided at the time of concussion diagnosis. Incorporating a standardized visiovestibular assessment into practice could facilitate early targeted school accommodations and thereby improve return to learning for elementary school-aged children with concussion.

Maintaining the essential functions of mitochondria requires mechanisms to recognize and remove misfolded proteins. However, quality control (QC) pathways for misfolded mitochondrial proteins remain poorly defined. Here, we establish temperature-sensitive (ts-) peripheral mitochondrial outer membrane (MOM) proteins as novel model QC substrates in Saccharomyces cerevisiae. The ts- proteins sen2-1HAts and sam35-2HAts are degraded from the MOM by the ubiquitin-proteasome system. Ubiquitination of sen2-1HAts is mediated by the ubiquitin ligase (E3) Ubr1, while sam35-2HAts is ubiquitinated primarily by San1. Mitochondria-associated degradation (MAD) of both substrates requires the SSA family of Hsp70s and the Hsp40 Sis1, providing the first evidence for chaperone involvement in MAD. In addition to a role for the Cdc48-Npl4-Ufd1 AAA-ATPase complex, Doa1 and a mitochondrial pool of the transmembrane Cdc48 adaptor, Ubx2, are implicated in their degradation. This study reveals a unique QC pathway comprised of a combination of cytosolic and mitochondrial factors that distinguish it from other cellular QC pathways., eLife digest Proteins are molecules that need to fold into the right shape to do their job. If proteins lose that shape, not only do they stop working but they risk clumping together and becoming toxic, potentially leading to disease. Fortunately, the cell has quality control systems that normally detect and remove misfolded proteins before they can cause damage to the cell. First, sets of proteins known as chaperones recognize the misfolded proteins, and then another class of proteins attaches a molecular tag, known as ubiquitin, to the misshapen proteins. When several ubiquitin tags are attached to a protein, forming chains of ubiquitin, it is transported to a large molecular machine within the cell called the proteasome. The proteasome unravels the protein and breaks it down into its constituent building blocks, which can then be used to create new proteins. Proteins are found throughout the different compartments of the cell and quality control processes have been well-studied in some parts of the cell but not others. Metzger et al. have now revealed how the process works on the surface of mitochondria, the compartment that provides the cell with most of its energy. To do this, they used baker’s yeast, a model laboratory organism that shares many fundamental properties with animal cells, but which is easier to manipulate genetically. The quality control process was studied using two mitochondrial proteins that had been mutated to make them sensitive to changes in temperature. This meant that, when the temperature increased from 25°C to 37°C, these proteins would begin to unravel and trigger the clean-up operation. This approach has been used previously to understand the quality control processes in other parts of the cell. By removing different quality control machinery in turn from the yeast cells, Metzger et al. could detect which were necessary for the process on mitochondria. This showed that there were many similarities with how this process happen in other parts of the cell but that the precise combination of chaperones and enzymes involved was distinct. Furthermore, when the proteasome was not working, the misfolded proteins remained on the mitochondria, showing that they are not transported to other parts of the cell to be broken down. In the future, understanding this process could help to find potential drug targets for mitochondrial diseases. The next steps will be to see how well these findings apply to human and other mammalian cells.

Background Few previous studies have directly compared crash rates of older and younger novice drivers. To inform discussion about whether Graduated Driver Licensing (GDL) policies that are applied in the US for younger novice drivers should be applied to older novice drivers, we conducted a longitudinal study to examine overall, nighttime, and multiple passenger crash rates over the initial four years of licensure differ for novice drivers licensed at different ages. Methods Using data from the New Jersey Traffic Safety Outcomes (NJ-TSO) data warehouse, we selected all NJ drivers who obtained their initial intermediate driver’s license from 2006 through 2014 and had at least one month of follow-up from the date of licensure to study end or death (n = 1,034,835). Novice drivers were grouped based on age at licensure: age 17; 18–20; 21–24; and 25 or older. We estimated monthly rates for overall crashes (per 10,000 licensed drivers) as well as: late night crashes (11:01 p.m.–4:59 a.m.); early night crashes (9:00 p.m.–11:00 p.m.); and multiple passenger crashes (two or more passengers). Average monthly rates were calculated for specific relevant time periods and Poisson regression models were used to compare rates: (1) between novice driver groups with the same time since licensure; (2) over the first 48 months of licensure within each novice driver group; and (3) between same-aged 21-year-old drivers with varying lengths of licensure. Results Although initial (three months post-licensure) overall crash rates of novice NJ drivers age 21 and older were higher than rates of same-aged experienced drivers, they were substantially lower than initial rates for 17- to 20-year-old novice drivers, who are licensed under GDL policies. Moreover, older novice drivers experience much less steep crash reductions over the first year of licensure than younger novice drivers. Nighttime crash rates among the 21- to 24-year old and aged 25 and older novice driver groups were stable over the first year of licensure. For novice drivers under age 21, early night crash rates declined rapidly over the course of licensure, while changes in late night crashes were much smaller. First-year multiple passenger crash rates were highest for drivers licensed at age 18–20, and novice driver groups experienced varying amounts of reduction in multiple passenger crashes over time. Conclusions Study findings support NJ’s current GDL policies for 17- to 20-year-old novice drivers and the potential for added benefits from beginning the nighttime restriction at 9:00 p.m. Conversely, there was a lack of compelling evidence for additional policies for drivers licensed at age 21–24 and no evidence to indicate a need for additional GDL policies for NJ novices aged 25 years and older.

Primary care providers are increasingly providing youth concussion care but report insufficient time and training, limiting adoption of best practices. We implemented a primary care–based intervention including an electronic health record–based clinical decision support tool (“SmartSet”) and in-person training. We evaluated consequent improvement in 2 key concussion management practices: (1) performance of a vestibular oculomotor examination and (2) discussion of return-to-learn/return-to-play (RTL/RTP) guidelines. Data were included from 7284 primary care patients aged 0 to 17 years with initial concussion visits between July 2010 and June 2014. We compared proportions of visits pre- and post-intervention in which the examination was performed or RTL/RTP guidelines provided. Examinations and RTL/RTP were documented for 1.8% and 19.0% of visits pre-intervention, respectively, compared with 71.1% and 72.9% post-intervention. A total of 95% of post-intervention examinations were documented within the SmartSet. An electronic clinical decision support tool, plus in-person training, may be key to changing primary care provider behavior around concussion care.

Prior studies have found disparities in child restraint system (CRS) use by individual-level factors like race/ethnicity and income. However, it is unclear if CRS use varies at the community or nei...

OBJECTIVE: Impairments generally persist when children diagnosed with attention-deficit/hyperactivity disorder (ADHD) mature into adolescence. To examine changes in ADHD care during the transition from childhood to adolescence, we conducted a retrospective, longitudinal cohort study of patients diagnosed with ADHD before the age of 10 years to assess changes from preadolescence through adolescence in (1) frequency by which primary care providers offer ADHD care to patients, (2) range of concerns assessed during patient encounters, and (3) treatments implemented or recommended. METHODS: We identified patients from 3 practices included in a large primary care network who (1) were born between 1996 and 1997, (2) were diagnosed with ADHD before the age of 10 years, and (3) received primary care continuously from age 9 through late adolescence. Clinical care was compared among patients in preadolescence (age 9–11), early adolescence (age 12–14), and late adolescence (age 15–18). RESULTS: Children diagnosed with ADHD before the age of 10 years were less likely to have a documented visit for ADHD during late adolescence (41% of patients) compared with preadolescence (63%, p < 0.001). Evidence of monitoring for depression, suicide, and substance abuse increased from preadolescence to adolescence (p < 0.001) and occurred in about 90% of adolescent patients. However, monitoring for risky sexual activity occurred in only about 50% of adolescents. Discussions of medication diversion and driver readiness were essentially not documented. CONCLUSION: The findings raise concerns about how primary care providers manage adolescents with a history of ADHD. Improving monitoring of risky sexual behavior and driver readiness and providing patient education about medication diversion are needed.

Purpose Evaluate the discriminatory ability of two clinical measures and one device-based measure of gait and balance for concussed youth. Methods We enrolled 81 cases and 90 controls age 14-18 yr old from August 2017 to June 2018. Controls were recruited from a suburban high school, and cases were recruited from the concussion program of an academic pediatric tertiary care center. Tests included two clinical measures: 1) complex tandem gait, scored as sway/errors walking forward and backward eyes open and closed; 2) Modified Balance Error Scoring System (mBESS), scored as total number of errors on three standing tasks; and one device-based measure; 3) Modified Clinical Test of Sensory Interaction and Balance (mCTSIB) using the Biodex Biosway Balance System, scored as a sway index. Sensitivity, specificity, ideal cutpoint, and area under the receiver operating characteristic curve (AUC) were calculated for all test components. Results Ideal cutpoint for total number of sway/errors for tandem gait = 5, sensitivity 41%, specificity 90%. Ideal cutpoint for total mBESS errors = 4, sensitivity 55%, specificity 75%. Ideal cutpoint for mCTSIB = 1.37, sensitivity 37%, specificity 88%. Among each test, some individual components outperformed overall composites, in particular tandem gait (specificity forward eyes open = 99%, sensitivity backward eyes closed = 81%). Among the 40 cases and 65 controls with all three assessments, AUC (95% CI) for tandem gait = 0.63 (0.52,0.75), mBESS = 0.70 (0.60,0.81), and mCTSIB = 0.54 (0.42,0.66). Conclusions A device-based measure of balance did not produce better discriminatory ability than two clinical assessments. Complex tandem gait has the additional benefit of being an easy-to-perform and graded test with highly sensitive and specific individual components.

Introduction: An increasing number of middle-aged men are being screened for low testosterone levels and the number of prescriptions for various forms of testosterone replacement therapy (TRT) has increased dramatically over the last 10 years. However, the safety of TRT has come into question with some studies suggesting increased morbidity and mortality. Objective: Because the benefits of estrogen replacement in postmenopausal women and ovariectomized rodents are lost if there is an extended delay between estrogen loss and replacement, we hypothesized that TRT may also be sensitive to delayed replacement. Methods: We compared the effects of testosterone replacement after short-term (2 weeks) and long-term testosterone deprivation (LTTD; 10 weeks) in middle-aged male rats on cerebral ischemia, oxidative stress, and cognitive function. We hypothesized that LTTD would increase oxidative stress levels and abrogate the beneficial effects of TRT. Results: Hypogonadism itself and TRT after short-term castration did not affect stroke outcome compared to intact rats. However, after long-term hypogonadism in middle-aged male Fischer 344 rats, TRT exacerbated the detrimental behavioral effects of experimental focal cerebral ischemia, whereas this detrimental effect was prevented by administration of the free-radical scavenger tempol, suggesting that TRT exacerbates oxidative stress. In contrast, TRT improved cognitive performance in non-stroked rats regardless of the length of hypogonadism. In the Morris water maze, peripheral oxidative stress was highly associated with decreased cognitive ability. Conclusions: Taken together, these data suggest that TRT after long-term hypogonadism can exacerbate functional recovery after focal cerebral ischemia, but in the absence of injury can enhance cognition. Both of these effects are modulated by oxidative stress levels.

OBJECTIVES:To compare monthly rates of specific types of crashes, violations, and license suspensions over the first years of licensure for drivers with and without attention-deficit/hyperactivity disorder (ADHD).METHODS:We identified patients of New Jersey primary care locations of the Children’s Hospital of Philadelphia who were born in 1987–1997, were New Jersey residents, had their last primary care visit at age ≥12 years, and acquired a driver’s license (N = 14 936). Electronic health records were linked to New Jersey’s licensing, crash, and violation databases. ADHD diagnosis was based on International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes. We calculated monthly per-driver rates of crashes (at fault, alcohol related, nighttime, and with peers), violations, and suspensions. Adjusted rate ratios were estimated by using repeated-measures Poisson regression.RESULTS:Crash rates were higher for drivers with ADHD regardless of licensing age and, in particular, during the first month of licensure (adjusted rate ratio: 1.62 [95% confidence interval: 1.18−2.23]). They also experienced higher rates of specific crash types: their 4-year rate of alcohol-related crashes was 2.1 times that of drivers without ADHD. Finally, drivers with ADHD had higher rates of moving violations (for speeding, seat belt nonuse, and electronic equipment use) and suspensions. In the first year of driving, the rate of alcohol and/or drug violations was 3.6 times higher for adolescents with ADHD.CONCLUSIONS:Adolescents with ADHD are at particularly high crash risk in their initial months of licensure, and engagement in preventable risky driving behaviors may contribute to this elevated risk. Comprehensive preventive approaches that extend beyond current recommendations are critically needed.

BackgroundDespite substantial progress, motor vehicle crashes remain a leading killer of US children. Previously, we documented significant positive impacts of Safe Routes to School interventions on school-age pedestrian and pedalcyclist crashes.ObjectiveTo expand our analysis of US trends in motor vehicle crashes involving school-age pedestrians and pedalcyclists, exploring heterogeneity by age and geography.MethodsWe obtained recent police-reported crash data from 26 states, calculating population rates of pedestrian and pedalcyclist crashes, crash fatality rates and pedestrian commuter-adjusted crash rates (‘pedestrian danger index’) for school-age children as compared with other age groups. We estimated national and statewide trends by age, injury status, day and travel hour using hierarchical linear modeling.ResultsSchool-age children accounted for nearly one in three pedestrians and one in two pedalcyclists struck in motor vehicle crashes from 2000 to 2014. Yet, the rates of these crashes declined 40% and 53%, respectively, over that time, on average, even as adult rates rose. Average crash rates varied geographically from 24.4 to 100.8 pedestrians and 15.6 to 56.7 pedalcyclists struck per 100 000 youth. Crash rates and fatality rates were inversely correlated.ConclusionsDespite recent increases in adult pedestrian crashes, school-age and younger pedestrians experienced ongoing declines in motor vehicle crashes through 2014 across the USA. There was no evidence of displacement in crash severity; declines were observed in all outcomes. The growing body of state crash data resources can present analytic challenges but also provides unique insights into national and local pedestrian crash trends for all crash outcomes.