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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.

Special Issue: The ENIGMA Consortium: the first 10 years., Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes., European Community's Seventh Framework Programme, Grant/Award Numbers: 278948, 602450, 603016, 602805; US National Institute of Child Health and Human Development, Grant/Award Numbers: RO1HD050735, 1009064, 496682; QIMR Berghofer Medical Research Institute and the Centre for Advanced Imaging, University of Queensland; ICTSI NIH/NCRR, Grant/Award Number: RR025761; European Community's Horizon 2020 Programme, Grant/Award Numbers: 667302, 643051; Vici Innovation Program, Grant/Award Numbers: #91619115, 016-130-669; NWO Brain & Cognition Excellence Program, Grant/Award Number: 433-09-229; Biobanking and Biomolecular Resources Research Infrastructure (Netherlands) (BBMRI-NL); Spinozapremie, Grant/Award Number: NWO-56-464-14192; Biobanking and Biomolecular Resources Research Infrastructure, Grant/Award Numbers: 184.033.111, 184.021.007; Netherlands Organization for Health Research and Development (ZonMW), Grant/Award Numbers: 480-15-001/674, 024.001.003, 911-09-032, 056-32-010, 481-08-011, 016-115-035, 31160008, 400-07-080, 400-05-717, 451-04-034, 463-06-001, 480-04-004, 904-61-193, 912-10-020, 985-10-002, 904-61-090; NIMH, Grant/Award Number: R01 MH090553; Geestkracht programme of the Dutch Health Research Council, Grant/Award Number: 10-000-1001; FP7 Ideas: European Research Council; Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Grant/Award Numbers: NWO/SPI 56-464-14192, NWO-MagW 480-04-004, 433-09-220, NWO 51.02.062, NWO 51.02.061; National Center for Advancing Translational Sciences, National Institutes of Health, Grant/Award Number: UL1 TR000153; National Center for Research Resources; National Center for Research Resources at the National Institutes of Health, Grant/Award Numbers: NIH 1U24 RR025736-01, NIH 1U24 RR021992; NIH Institutes contributing to the Big Data to Knowledge; U.S. National Institutes of Health, Grant/Award Numbers: R01 CA101318, P30 AG10133, R01 AG19771; Medical Research Council, Grant/Award Numbers: U54EB020403, G0500092; National Institute of Mental Health, Grant/Award Numbers: R01MH117014, R01MH042191; Fundación Instituto de Investigación Marqués de Valdecilla, Grant/Award Numbers: API07/011, NCT02534363, NCT0235832; Instituto de Salud Carlos III, Grant/Award Numbers: PI14/00918, PI14/00639, PI060507, PI050427, PI020499; Swedish Research Council, Grant/Award Numbers: 523-2014-3467, 2017-00949, 521-2014-3487; South-Eastern Norway Health Authority; the Research Council of Norway, Grant/Award Number: 223273; South Eastern Norway Regional Health Authority, Grant/Award Numbers: 2017-112, 2019107; Icahn School of Medicine at Mount Sinai; Seventh Framework Programme (FP7/2007-2013), Grant/Award Number: 602450; National Institutes of Health, Grant/Award Numbers: R01 MH116147, R01 MH113619, R01 MH104284; South London and Maudsley NHS Foundation Trust; the National Institute for Health Research (NIHR)

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.

PURPOSE: Older cancer patients are susceptible to long-term effects of chemotherapy, including cancer-related cognitive decline and impairments to quality of life. Taxane-based chemotherapies are associated with physical declines among older women and may negatively impact cognitive performance. We sought to examine whether changes in objective and subjective measures of cognitive performance and well-being differ among older breast cancer survivors as a function of taxane-based chemotherapy treatment regimens. METHODS: Individual-level data was pooled and harmonized from two large prospective studies of older (greater than 60 years) breast cancer survivors. Assessments were conducted prior to systemic therapy and up to 36-months after. Cognitive performance was assessed with objective (working memory, processing speed and executive functions) and subjective tests and physical, emotional and functional well-being was also assessed. RESULTS: One hundred and sixty-seven (M age = 67.3 years) women, with 116 receiving chemotherapy with taxanes and 51 without taxanes contributed data. Declines in subjective cognition for both groups were significant between pre-treatment and 12-month follow-up. Significant improvements were seen on a measure of objective cognition (working memory) from 12 to 36-months. Measures of well-being improved from prior to systemic therapy to 12-months. Longitudinal changes across all measures did not vary as a function of receipt of taxane-based treatment. CONCLUSION: Older women who received treatment with taxanes did not have greater declines in cognitive performance or well-being than women receiving other chemotherapy regimens. Despite older cancer survivors being at greater risk for negative outcomes, treatment with taxane-based chemotherapies does not appear to exacerbate these health consequences.

PurposeOlder cancer survivors required medical care during the COVID-19 pandemic despite infection risks, but there are limited data on medical care in this age group. Methods. We evaluated care disruptions in a longitudinal cohort of non-metastatic breast cancer survivors ages 60-98 from five US regions (n=321). Survivors completed a web-based or telephone survey from May 27, 2020 to September 11, 2020. Care disruptions included self-reported interruptions in ability to see doctors, receive treatment or supportive therapies, or fill prescriptions. Logistic regression models evaluated bivariate and multivariate associations between care disruptions and education, medical, psychosocial and COVID-19-related factors. Multivariate models included age, county COVID-19 rates, comorbidity and post-diagnosis time. Results. There was a high response rate (n=262, 81.6%). Survivors were 32.2 months post-diagnosis (SD 17.5, range 4-73). Nearly half (48%) reported a medical disruption. The unadjusted odds of care disruptions were significantly higher with more education (OR 1.23 per one-year increase, 95% CI 1.09-1.39, p =0.001) and greater depression (OR 1.04 per one-point increase in CES-D score, CI 1.003-1.08, p=0.033); tangible support decreased the odds of disruptions (OR 0.99, 95% CI 0.97-0.99 per one-point increase, p=0.012). There was a trend for associations between disruptions and comorbidity (unadjusted OR 1.13 per 1 added comorbidity, 95% CI 0.99-1.29, p=0.07). Adjusting for covariates, only higher education (p=0.001) and tangible social support (p=0.006) remained significantly associated with having care disruptions. Conclusions. Older breast cancer survivors reported high rates of medical care disruptions during the COVID-19 pandemic and psychosocial factors were associated with care disruptions.

Objective To determine the relationship between patient characteristics and performance on the visio-vestibular examination (VVE) in a cohort of healthy youth athletes and explore the potential association between the VVE and other standardized concussion batteries. Design Cross-sectional. Setting Suburban middle and high school. Patients One hundred ninety subjects age 11 to 18 enrolled before their respective scholastic sport season between August 2017 and March 2020. Assessment of independent variables Patient age, sex, concussion history, comorbidities, hours of weekly exercise, Sport Concussion Assessment Tool, 5th edition (SCAT-5), King-Devick (K-D), Postconcussion Symptom Inventory (PCSI). Main outcome measures Visio-vestibular examination abnormalities (smooth pursuit, horizontal and vertical saccades, horizontal and vertical gaze stability, convergence, right and left monocular accommodation, complex tandem gait). Results Overall, 29.5% of subjects had at least one of 9 VVE elements abnormal, 7.9% at least 2, and 3.2% at least 3. None of 72 comparisons of the VVE elements, when stratified by age, sex, concussion history, history of headaches, attention deficit hyperactivity disorder, learning issues, psychiatric problems, motion sickness, or weekly hours of exercise, reached significance using the Benjamini-Hochberg procedure at a false discovery rate of 5%. There were no significant associations between VVE elements and the SCAT-5, K-D, or PCSI. Conclusions The VVE is robust across multiple patient characteristics. Although healthy subjects may have one abnormal element, multiple abnormal elements are a less common feature, making multiple abnormal elements more indicative of concussion, highlighting the use of this assessment in the setting of injury. The VVE tests unique domains when compared with the PCSI, SCAT-5, and K-D.

Introduction Current standards for identifying recent cannabis use are based on body fluid testing. The Cognalyzer® is a novel electroencephalography (EEG) measurement device and algorithm designed to objectively characterize brainwave alterations associated with cannabis. The objective of this study was to assess the accuracy, sensitivity and specificity levels of the Cognalyzer® to characterize brainwave alterations following cannabis inhalation. Methods Seventy-five participants, aged 19–55 years, were enrolled, and oral fluid samples were collected pre-cannabis inhalation. EEG and subjective drug effects questionnaire (DEQ) were administered pre- and post-ad libitum cannabis inhalation. Fifty participants remained in the clinic for 4 h post-inhalation. Blinded analyses of the EEG files were conducted by Zentrela Inc. using two versions (V1 and V2) of the Cognalyzer® algorithm. Pre- vs. post-inhalation comparison status was characterized by the Cognalyzer® and summarized for: sensitivity, specificity, accuracy, percent false positive, percent false negative and positive and negative predictive value. The null hypothesis was tested using McNemar’s test. Cognalyzer® results pre- and post-inhalation were combined with the oral fluid tetrahydrocannabinol (THC) concentration to evaluate potential to improve current drug testing. Results The two versions of the Cognalyzer® algorithm had similar diagnostic results. Diagnostic outcomes were improved when participants with missing EEG recordings or electrode placement errors were removed. The Cognalyzer® accuracy was 85.5% and 83.9%, sensitivity was 87.1% and 88.7%, and specificity was 83.9% and 79.0% for algorithm V1 and V2, respectively. Combining Cognalyzer® results with oral fluid concentrations reduced false-positive oral fluid test results by up to 49%. Conclusion The Cognalyzer® characterized brainwave alterations associated with cannabis inhalation with high levels of accuracy in a population of participants with varied cannabis inhalation histories, relative to the comparison standard of pre- vs. post-inhalation status. The Cognalyzer® allows the results to be generalized to the larger population addressing a limitation in currently accepted standards.

Cancer- and treatment-related cognitive dysfunction (CRCD) is a common challenge faced by patients diagnosed with non-central nervous system (CNS) cancer. It has become increasingly recognized that multiple factors likely play a role in these symptoms, including the cancer disease process, systemic treatments (e.g., chemotherapy and endocrine therapies), and risk factors that may predispose an individual to both cancer and cognitive dysfunction. As the field has evolved, advanced neuroimaging techniques have been applied to better understand the neural correlates of CRCD. This review focuses on structural neuroimaging findings related to CRCD in adult non-CNS cancer populations, including examination of gray matter volume/density and white matter integrity differences between cancer patients and comparison groups, as well as emerging findings regarding structural network abnormalities. Overall, this literature has demonstrated consistent findings of reduced gray matter volume/density and white matter integrity in cancer patients relative to comparison groups. These are most prominent in individuals treated with chemotherapy, though alterations have also been noted in those treated with anti-estrogen and androgen-deprivation therapies. Alterations in gray and white matter structural network connectivity have also been identified. These structural abnormalities have been observed most prominently in frontal and temporal brain regions, and have been shown to correlate with subjective and objective cognitive function, as well as with physiological and clinical variables, helping to inform understanding of CRCD mechanisms. To date, however, structural neuroimaging techniques have not been utilized in systematic studies of potential CRCD treatments, suggesting a potentially fruitful avenue for future research. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-021-01096-5.

The use of two attending surgeons during posterior spinal fusion (PSF) for cerebral palsy (CP) patients has been shown to improve perioperative outcomes. This study aims to determine if the use of two surgeons is associated with an increase in the number of subsequent surgeries that can be performed in the same operating room (OR) during business hours. Patients with scoliosis and CP treated with PSF with minimum 90-day follow-up were included. Patients were grouped based on whether one or two attending surgeons performed the case. The primary outcome was the number of surgeries that followed in the same OR before 5 PM. Secondary outcomes included operative time, estimated blood loss (EBL), length of stay, rate of surgical site infection, and rate of unplanned return to the operating room. Thirty-six patients were included (10 with 1 surgeon and 26 with 2 surgeons). The two surgeon group had a significant increase in the average number of surgeries subsequently performed in the same OR during business hours (1.1 vs. 0.3, p = 0.01), as well as shorter mean operative time (159 vs. 307 min, p = 0.007) and EBL (554 vs. 840 cc, p = 0.01; 26 vs. 39%EBV, p = 0.03). The use of two attending surgeons was associated with a significant increase in the number of cases subsequently performed in the same OR during business hours, and significant decreases in operative time and EBL. Hospitals should consider the patient care and potential system-level improvements when considering implementation of two surgeon teams for PSF in CP patients. Therapeutic Level III.

Background We evaluated deficit accumulation and how deficits affected cognition and physical activity among breast cancer survivors and non-cancer controls. Methods Newly diagnosed nonmetastatic survivors (n = 353) and matched non-cancer controls (n = 355) ages 60-98 years without neurological impairments were assessed presystemic therapy (or at enrollment for controls) from August 2010 to December 2016 and followed for 36 months. Scores on a 42-item index were analyzed in growth-mixture models to determine deficit accumulation trajectories separately and combined for survivors and controls. Multilevel models tested associations between trajectory and cognition (FACT-Cog and neuropsychological tests) and physical activity (IPAQ-SF) for survivors and controls. Results Deficit accumulation scores were in the robust range, but survivors had higher scores (95% confidence intervals [CI]) than controls at 36 months (0.18, 95% CI = 0.16 to 0.19, vs 0.16, 95% CI = 0.14 to 0.17; P = .001), and averages included diverse deficit trajectories. Survivors who were robust but became frailer (8.8%) had similar baseline characteristics to those remaining robust (76.2%) but experienced a 9.6-point decline self-reported cognition (decline of 9.6 vs 3.2 points; P = .04) and a 769 MET minutes per week decline in physical activity (P < .001). Survivors who started and remained prefrail (15.0%) had self-reported and objective cognitive problems. At baseline, frail controls (9.5%) differed from robust controls (83.7%) on deficits and self-reported cognition (P < .001). Within combined trajectories, frail survivors had more sleep disturbances than frail controls (48.6% [SD = 17.4%] vs 25.0% [SD = 8.2%]; P = .05). Conclusions Most survivors and controls remained robust, and there were similar proportions on a frail trajectory. However, there were differences in deficit patterns between survivors and controls. Survivor deficit accumulation trajectory was associated with patient-reported outcomes. Additional research is needed to understand how breast cancer and its treatments affect deficit accumulation.

To further the understanding of long-term sequelae as a result of repetitive head impacts in sports, in vivo head impact exposure data are critical to expand on existing evidence from animal model and laboratory studies. Recent technological advances have enabled the development of head impact sensors to estimate the head impact exposure of human subjects in vivo. Previous research has identified the limitations of filtering algorithms to process sensor data. In addition, observer and/or video confirmation of sensor-recorded events is crucial to remove false positives. The purpose of the current study was to conduct a systematic review to determine the proportion of published head impact sensor data studies that used filtering algorithms, observer confirmation and/or video confirmation of sensor-recorded events to remove false positives. Articles were eligible for inclusion if collection of head impact sensor data during live sport was reported in the methods section. Descriptive data, confirmation methods and algorithm use for included articles were coded. The primary objective of each study was reviewed to identify the primary measure of exposure, primary outcome and any additional covariates. A total of 168 articles met the inclusion criteria, the publication of which has increased in recent years. The majority used filtering algorithms (74%). The majority did not use observer and/or video confirmation for all sensor-recorded events (64%), which suggests estimates of head impact exposure from these studies may be imprecise.

INTRODUCTION: Concern surrounding short- and long-term consequences of participation in contact sports has become a significant public health topic. Previous literature utilizing diffusion tensor imaging in sports-related concussion has exhibited notable variety of analysis methods and analyzed regions of interest, and largely focuses on acute effects of concussion. The current study aimed to compare diffusivity metrics across a single season within athlete cohorts with no history of concussion. METHODS: A prospective cohort of 75 contact and 79 non-contact division I athletes were compared across diffusion tensor imaging metrics (i.e., TRACULA); examinations were also performed assessing the relationship between neuroimaging metrics, head impact exposure metrics (in-helmet accelerometer), and neurocognitive variables. Assessment occurred at pre-and post-season time points. RESULTS: Seasonal changes in fractional anisotropy and mean diffusivity values did not differ between athlete cohorts, nor did they differ within cohort groups, across pre- and post-season scans. Specific to contact athletes, positive associations were found between uncinate fasciculus mean diffusivity values and season linear acceleration (p = .018), season rotational acceleration (p = .017), and season hit severity (p = .021). CONCLUSIONS: Results suggest an influence of impact frequency, type, and severity on white matter integrity in select brain regions in contact athletes. Current findings expand our knowledge of anatomical changes over the course of a single season, and underscore the importance of considering methodology when interpreting findings in this population, as differing image analysis techniques may lead to different conclusions regarding significant effects.

Background. Many of the approaches available for modifying manual materials handling (MMH) exertion emphasize lower back protection but often do not consider how interventions affect other body reg...

Background Transportation barriers prevent millions of people from accessing health care each year. Health policy innovations such as shared savings payment models (commonly used in accountable care organizations) present financial incentives for providers to offer patient transportation to medical care. Meanwhile, ridesourcing companies like Uber and Lyft have entered the market to capture a significant share of spending on non-emergency health care transportation. Our research examines the current landscape of innovative health care mobility services in the US. Methods We conducted an environmental scan to identify case examples of utilization of ridesourcing technology to facilitate non-emergency health care transportation and developed a typology of innovative health care mobility services. The scan used a keyword-based search of news publications with inductive analysis. For each instance identified, we abstracted key information including: stakeholders, launch date, transportation provider, location/service area, payment/booking method, target population, level of service, and any documented outcomes. Results We discovered 53 cases of innovation and among them we identified three core types of innovation or collaboration. The first and most common type of innovation is when a health care provider leverages ridesourcing technology to book patient trips. This involves both established and nascent transportation companies tailoring the ridesourcing experience to the health care industry by adding HIPAA-compliance to the booking process. The second type of innovation involves an insurer or health plan formally partnering with a ridesourcing company to expand transportation offerings to beneficiaries or offer these services for the first time. The third type of innovation is when a paratransit provider partners with a ridesourcing company; these cases cite increased flexibility and reliability of ridesourcing services compared to traditional paratransit. Conclusions Ridesourcing options are becoming a part of the mode choice set for patients through formal partnerships between ridesourcing companies, health care providers, insurers, and transit agencies. The on-demand nature of rides, booking flexibility, and integration of ride requests and payment options via electronic medical records appear to be the strongest drivers of this innovation.

Background To assess: (a) cancer treatment in prostate cancer survivors (PCS) by age at diagnosis (ADx) and prostate cancer (PC) aggressiveness; (b) potential impact on PC mortality; and (c) these results in the context of environmental/behavioral risk factors on PCS in Pennsylvania. Methods Prostate cancer survivors ages ≥40 years were identified from the 2004‐2014 Pennsylvania Cancer Registry (PCR). Demographic/clinical descriptors and PC treatment were extracted from PCR. Prostate cancer aggressiveness was defined by clinical/pathologic Gleason score and tumor stage. Logistic and Cox regression analyses tested associations between treatment received and PC‐specific mortality. County‐level data from the Pennsylvania BRFSS were used to estimate cancer‐related behavioral risk factors (eg, smoking, physical inactivity, fruit/vegetable consumption [FV], alcohol use) and used as covariates. Results There were 90 694 PCS ages 40‐105 years (mean age = 66.19 years, SD = 9.25) included. Most were non‐Hispanic white men (83%). Prostate cancer survivors ≥75 years were least likely to receive any treatment but men ages 65‐74 were more likely to receive combined therapies (OR = 1.47; 95% CI 1.28, 1.69) vs PCS ages 40‐54 years, controlling for covariates. Prostate cancer survivors 55‐75+ with aggressive PC who received any treatment vs no definitive treatment had significantly reduced mortality. Men from counties with high obesity and smoking rates were significantly less likely to receive any treatment than men living in counties with lower rates of these risk factors. Prostate cancer survivors who lived in counties with high rates of physical inactivity and had high rates of sufficient FV consumption were slightly more likely to receive cancer treatment vs no definitive treatment compared to men who lived in counties with high rates of physical activity and lower FV consumption. Conclusions We observed a general age‐related decline in receipt of treatment. Prostate cancer survivors ages ≥75 years were significantly less likely to get any cancer treatment compared to younger PCS. However, most men with more aggressive disease who received any treatment had greatly reduced PC mortality, regardless of age. Considering environmental/behavioral risk factors may attenuate PC risk and inform treatment options., We analyzed prostate cancer registry data for >90 000 men ages 40‐105 to understand age‐related associations with disease aggressiveness, treatment and potential role of environmental/behavioral risk factors in understanding likelihood of treatment recommendations and impact on mortality. Men older than 75 years were more likely to have aggressive disease but less likely to receive any treatment. The oldest men also had the greatest survival benefits from any treatment. We also provide insight on whether where you live impacts your treatment and ultimate survival.

2019 Novel Coronavirus (2019-nCoV) is an emerging infectious disease closely related to MERS-CoV and SARS-CoV that was first reported in Wuhan City, Hubei Province, China in December 2019. As of January 2020, cases of 2019-nCoV are continuing to be reported in other Eastern Asian countries as well as in the United States, Europe, Australia, and numerous other countries. An unusually high volume of domestic and international travel corresponding to the beginning of the 2020 Chinese New Year complicated initial identification and containment of infected persons. Due to the rapidly rising number of cases and reported deaths, all countries should be considered at risk of imported 2019-nCoV. Therefore, it is essential for prehospital, clinic, and emergency department personnel to be able to rapidly assess 2019-nCoV risk and take immediate actions if indicated. The Identify-Isolate-Inform (3I) Tool, originally conceived for the initial detection and management of Ebola virus and later adjusted for other infectious agents, can be adapted for any emerging infectious disease. This paper reports a modification of the 3I Tool for use in the initial detection and management of patients under investigation for 2019-nCoV. After initial assessment for symptoms and epidemiological risk factors, including travel to affected areas and exposure to confirmed 2019-nCoV patients within 14 days, patients are classified in a risk-stratified system. Upon confirmation of a suspected 2019-nCoV case, affected persons must immediately be placed in airborne infection isolation and the appropriate public health agencies notified. This modified 3I Tool will assist emergency and primary care clinicians, as well as out-of-hospital providers, in effectively managing persons with suspected or confirmed 2019-nCoV.

Tumor biopsies are an important aspect of oncology providing a guide for medical treatment and evaluation of disease progression. Highly heterogenous tumors have complex regions of active cancer cells interdigitated with necrotic tissue and healthy noncancerous tissue. The reliable access to tumor tissue pathology is therefore challenging and usually requires multiple needle insertions with accompanying patient discomfort and risk of infection. Oxygen levels provide a means of detecting and evaluating tumor tissue with levels reduced by 2-fold to 22-fold, depending on the type of organ. However, if the biopsy needle is placed in an area of normal tissue, there is always a chance that no diagnostic cells will be acquired for meaningful pathology and molecular analysis. While not the case in all tumors, there are cases where the in vivo oxygen levels differ with tumor cells having a value of pO2 lying between the anoxic necrotic tissue and normoxic normal tissue. The level of oxygen in tumor cells can also vary with time as related to complex biochemical pathways. The efficacy of radiation therapy is also sensitive to oxygen levels in tumors. Lower levels of oxygen present greater resistance to treatment. To address these concerns, a pO2-guided biopsy needle (OGBN) was developed to determine oxygen levels and fluctuations in highly resolved regions of tumors, in order to aide in determining the optimal region for cell sampling help in determining medical treatment options.

Background Sexual-size dimorphism (SSD) is replete among animals, but while the selective pressures that drive the evolution of SSD have been well studied, the developmental mechanisms upon which these pressures act are poorly understood. Ours and others’ research has shown that SSD in D. melanogaster reflects elevated levels of nutritional plasticity in females versus males, such that SSD increases with dietary intake and body size, a phenomenon called sex-specific plasticity (SSP). Additional data indicate that while body size in both sexes responds to variation in protein level, only female body size is sensitive to variation in carbohydrate level. Here, we explore whether these difference in sensitivity at the morphological level are reflected by differences in how the insulin/IGF-signaling (IIS) and TOR-signaling pathways respond to changes in carbohydrates and proteins in females versus males, using a nutritional geometry approach. Results The IIS-regulated transcripts of 4E-BP and InR most strongly correlated with body size in females and males, respectively, but neither responded to carbohydrate level and so could not explain the sex-specific response to body size to dietary carbohydrate. Transcripts regulated by TOR-signaling did, however, respond to dietary carbohydrate in a sex-specific manner. In females, expression of dILP5 positively correlated with body size, while expression of dILP2,3 and 8, was elevated on diets with a low concentration of both carbohydrate and protein. In contrast, we detected lower levels of dILP2 and 5 protein in the brains of females fed on low concentration diets. We could not detect any effect of diet on dILP expression in males. Conclusion Although females and males show sex-specific transcriptional responses to changes in protein and carbohydrate, the patterns of expression do not support a simple model of the regulation of body-size SSP by either insulin- or TOR-signaling. The data also indicate a complex relationship between carbohydrate and protein level, dILP expression and dILP peptide levels in the brain. In general, diet quality and sex both affect the transcriptional response to changes in diet quantity, and so should be considered in future studies that explore the effect of nutrition on body size.

BACKGROUND Little is known about longitudinal symptom burden, its consequences for well-being, and whether lifestyle moderates the burden in older survivors. METHODS The authors report on 36-month data from survivors aged ≥60 years with newly diagnosed, nonmetastatic breast cancer and noncancer controls recruited from August 2010 through June 2016. Symptom burden was measured as the sum of self-reported symptoms/diseases as follows: pain (yes or no), fatigue (on the Functional Assessment of Cancer Therapy [FACT]-Fatigue scale), cognitive (on the FACT-Cognitive scale), sleep problems (yes or no), depression (on the Center for Epidemiologic Studies Depression scale), anxiety (on the State-Trait Anxiety Inventory), and cardiac problems and neuropathy (yes or no). Well-being was measured using the FACT-General scale, with scores from 0 to 100. Lifestyle included smoking, alcohol use, body mass index, physical activity, and leisure activities. Mixed models assessed relations between treatment group (chemotherapy with or without hormone therapy, hormone therapy only, and controls) and symptom burden, lifestyle, and covariates. Separate models tested the effects of fluctuations in symptom burden and lifestyle on function. RESULTS All groups reported high baseline symptoms, and levels remained high over time; differences between survivors and controls were most notable for cognitive and sleep problems, anxiety, and neuropathy. The adjusted burden score was highest among chemotherapy-exposed survivors, followed by hormone therapy-exposed survivors versus controls (P

BACKGROUND Obesity rates continue to rise among children and adolescents across the globe. A multicenter research consortium composed of institutions in the Southern US, located in states endemic for childhood obesity, was formed to evaluate the effect of obesity on pediatric musculoskeletal disorders. This study evaluates the effect of body mass index (BMI) percentile and socioeconomic status (SES) on surgical site infections (SSIs) and perioperative complications in patients with adolescent idiopathic scoliosis (AIS) treated with posterior spinal fusion (PSF). METHODS Eleven centers in the Southern US retrospectively reviewed postoperative AIS patients after PSF between 2011 and 2017. Each center contributed data to a centralized database from patients in the following BMI-for-age groups: normal weight (NW, 5th to

Active duty military members have significant service-related risks for developing pain from injury. Although estimates for neuropathic pain (NP) are available for civilian populations, the incidence and prevalence for NP in military members is less clear. Understanding correlates of pain in military members is vital to improving their physical, mental, and social health. Using a comparative design, a secondary analysis was conducted on longitudinal PASTOR data from 190 pain management center patients. The objectives were to compare trends in patient-reported outcomes over time between those screening positive and negative for NP (NP+, NP−, respectively) based on PROMIS Neuropathic Pain Scale T-scores. Findings showed improvements in fatigue, sleep-related impairment, and anger over time. There was a difference between those screening NP+ and NP− for sleep-related impairment, and the cross-level interaction effect showed sleep-related impairment worsening over time. These results emphasize the need to identify NP and implement and evaluate targeted therapies.

Background: The National Healthcare Safety Network (NHSN) has used positive laboratory tests for surveillance of Clostridioides difficile infection (CDI) LabID events since 2009. Typically, CDIs are detected using enzyme immunoassays (EIAs), nucleic acid amplification tests (NAATs), or various test combinations. The NHSN uses a risk-adjusted, standardized infection ratio (SIR) to assess healthcare facility-onset (HO) CDI. Despite including test type in the risk adjustment, some hospital personnel and other stakeholders are concerned that NAAT use is associated with higher SIRs than EIA use. To investigate this issue, we analyzed NHSN data from acute-care hospitals for July 1, 2017, through June 30, 2018. Methods: Calendar quarters where CDI test type was reported as NAAT (includes NAAT, glutamate dehydrogenase (GDH)+NAAT and GDH+EIA followed by NAAT if discrepant) or EIA (includes EIA and GDH+EIA) were selected. HO-CDI SIRs were calculated for facility-wide inpatient locations. We conducted the following 2 analyses: (1) Among hospitals that did not switch their test type, we compared the distribution of HO incident rates and SIRs by those reporting NAAT versus EIA. (2) Among hospitals that switched their test type, we selected quarters with a stable switch pattern of 2 consecutive quarters of each of EIA and NAAT (categorized as EIA-to-NAAT or NAAT-to-EIA). Pooled semiannual SIRs for EIA and NAAT were calculated, and a paired t test was used to evaluate the difference in SIRs by switch pattern. Results: Most hospitals did not switch test types (3,242, 89%), and 2,872 (89%) reported sufficient data to calculate an SIR, with 2,444 (85%) using NAAT. The crude pooled HO CDI incidence rates for hospitals using EIAs clustered at the lower end of the histogram versus rates for NAATs (Fig. 1). The SIR distributions, both NAATs and EIAs, overlapped substantially and covered a similar range of SIR values (Fig. 1). Among hospitals with a switch pattern, hospitals were equally likely to have an increase or decrease in their SIRs (Fig. 2). The mean SIR difference for the 42 hospitals switching from EIA to NAAT was 0.048 (95% CI, −0.189 to 0.284; P = .688). The mean SIR difference for the 26 hospitals switching from NAAT to EIA was 0.162 (95% CI, −0.048 to 0.371; P = .124). Conclusions: The pattern of SIR distribution for both NAAT and EIA substantiate the soundness of the NHSN’s risk adjustment for CDI test types. Switching test type did not produce a consistent directional pattern in SIR that was statistically significant.Funding: NoneDisclosures: None

Few studies have reported temporal and spatial trends of aggressive prostate cancer (PC) among black men who are known to have more aggressive disease. We examined these trends for highly aggressive PC at diagnosis among black and white men in Pennsylvania (PA). Men, aged ≥ 40 years, with a primary, clinical PC diagnosis were identified from the Pennsylvania Cancer Registry, 2004–2014. Joinpoint analysis was used to evaluate the temporal trend of highly aggressive PC (clinical/pathologic Gleason score ≥ 7 [4 + 3], clinical/pathologic tumor stage ≥ T3, or distant metastasis) and identify change points by race in which annual percent change (APC) was calculated. Logistic regression analyses were used to examine the association between race and highly aggressive PC, after adjusting for covariates with and without spatial dependence. There were 89,133 PC cases, which included 88.7% white and 11.3% black men. The APC of highly aggressive PC was 8.7% from 2011 to 2014 among white men and 3.6% from 2007 to 2014 among black men (p values ≤ 0.01). The greatest odds of having highly aggressive PC among black compared to white men were found in counties where the black male population was ≤ 5.3%. Highly aggressive PC increased for both black and white men in PA between 2004 and 2014. Black men had more aggressive disease, with the greatest odds in counties where the black male population was small. The increase in highly aggressive PC may be due to less screening for PC, resulting in more advanced disease at diagnosis.

Objective: To systematically review and summarize articles evaluating the effectiveness of child restraint system (CRS) interventions targeting parents/caregivers’ knowledge of, overall rates of an...

Objectives To determine the failure rate of the DePuy-Synthes variable angle locking compression curved condylar plate (VA-LCP) and quantify failure modes. Design Retrospective review. Setting Level I Trauma Center. Patients/participants One hundred thirteen patients with 118 OTA/AO classification 33A and 33C distal femoral fractures were included in the study. Intervention Internal fixation using only the DePuy-Synthes VA-LCP plate. Main outcome measurements Primary outcomes included mechanical failure rate of the DePuy-Synthes VA-LCP plate in open and closed fractures. Secondary outcomes included overall failure rate of treatment, risk factors for mechanical failure, and the specific location of failure: loss of fixation in the proximal segment, implant failure over the working length, or failure of locking screw fixation distally. Results There were 11 total failures (9.3%) in 118 fractures. Failure rates for the closed and open fracture groups were 5.4% and 15.9%, respectively. Twenty patients (16.9%) required reoperation to promote union. Open fractures (P = 0.00475), the presence of medial metaphyseal comminution (P = 0.037), the length of the zone of comminution (P = 0.037), and plate length (P = 0.0096) were significantly higher in those with implant failure. Most failures (63.6%) were in the working length of the implant. Conclusions The use of the Synthes VA-LCP is a viable option in distal femoral fractures and has an acceptable failure rate and reoperation to promote union rate. Level of evidence Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Complex repetitive tasks are common in the workplace and have been associated with upper extremity disorders. The purpose of this study was to examine the progressive effects of highly repetitive work on joint kinematics and muscle activity of the trunk and upper extremity. Fifteen healthy men performed 60 one-minute cycles of 4 simulated automotive-related tasks. Electromyography of eight muscles and kinematics of the trunk and right upper extremity were collected. Data were analysed at 12-min intervals and divided into a complete work cycle. The time to complete the work cycle decreased by 6.3

The purpose of this study was to examine prescribing patterns and identify characteristics associated with an adolescent being prescribed an opioid at time of discharge from a hospital stay...

Introduction Staphylococcus aureus is one of the most common pathogens in health care facilities and in the community, and can cause invasive infections, sepsis, and death. Despite progress in preventing methicillin-resistant S. aureus (MRSA) infections in health care settings, assessment of the problem in both health care and community settings is needed. Further, the epidemiology of methicillin-susceptible S. aureus (MSSA) infections is not well described at the national level. Methods Data from the Emerging Infections Program (EIP) MRSA population surveillance (2005–2016) and from the Premier and Cerner Electronic Health Record databases (2012–2017) were analyzed to describe trends in incidence of hospital-onset and community-onset MRSA and MSSA bloodstream infections and to estimate the overall incidence of S. aureus bloodstream infections in the United States and associated in-hospital mortality. Results In 2017, an estimated 119,247 S. aureus bloodstream infections with 19,832 associated deaths occurred. During 2005–2012 rates of hospital-onset MRSA bloodstream infection decreased by 17.1% annually, but the decline slowed during 2013–2016. Community-onset MRSA declined less markedly (6.9% annually during 2005–2016), mostly related to declines in health care–associated infections. Hospital-onset MSSA has not significantly changed (p = 0.11), and community-onset MSSA infections have slightly increased (3.9% per year, p

CONTEXT: Mutations in melanocortin receptor (MC4R) are the most common cause of monogenic obesity in children of European ancestry, but little is known about their prevalence in children from the minority populations in the United States. OBJECTIVE: This study aims to identify the prevalence of MC4R mutations in children with severe early-onset obesity of African American or Latino ancestry. DESIGN AND SETTING: Participants were recruited from the weight management clinics at two hospitals and from the institutional biobank at a third hospital. Sequencing of the MC4R gene was performed by whole exome or Sanger sequencing. Functional testing was performed to establish the surface expression of the receptor and cAMP response to its cognate ligand α-melanocyte–stimulating hormone. PARTICIPANTS: Three hundred twelve children (1 to 18 years old, 50% girls) with body mass index (BMI) >120% of 95th percentile of Centers for Disease Control and Prevention 2000 growth charts at an age

Repetitive work is common in the modern workplace and the effects are often studied using fatigue protocols; however, there is evidence that the manner in which fatigue develops impacts the kinematic and muscular response to reduced physical capacity. The purpose of this study was to simultaneously evaluate muscular and kinematic adaptations during fatiguing, repetitive work until exhaustion. We measured muscle activity in 13 muscles in the shoulder and trunk, and captured full body kinematics while participants completed simulated, repetitive work tasks. Every 12 min, reference data were collected to quantify fatigue. This sequence continued until they reached the termination criteria. Participants displayed significant signs of muscle fatigue, loss of strength and increased perceived fatigue (p 0.05). Analysis revealed a significant effect of time on posture and muscle activity that was both task and time dependent, and variable both between and within individuals. Participants were able to compensate for reduced physical capacity and maintain task performance through coordinated compensation strategies.

Background: Obese patients with adolescent idiopathic scoliosis (AIS) have been shown to present with larger curve magnitudes preoperatively. However, the effect of obesity on shoulder balance in AIS remains unknown. The purpose of our study was to determine if overweight and obese patients with AIS have worse radiographic shoulder balance on initial presentation when compared with normal weight patients. Methods: AIS patients Results: One hundred eighty-four patients (116 [63%] normal weight and 68 [37%] overweight/obese) were included. The mean age at surgery was 13.1 ± 2 years, and mean follow-up was 17.4 ± 13 months. Preoperative shoulder imbalance was significantly greater in the overweight/obese group compared to the normal weight group (1.9 ± 1 cm vs. 1.5 ± 1 cm, p = 0.04). The odds ratio of presenting with unbalanced shoulders was 2.0 (95% CI: 1.02–3.83, p = 0.04) for the overweight/obese group. No significant differences were found for postoperative shoulder balance, UIV selection, or major curve correction. Conclusions: Overweight and obese patients with AIS are twice as likely to present with unbalanced shoulders preoperatively; however, this difference is not clinically relevant with a mean difference of 0.4 cm between cohorts. Finally, the preoperative BMI percentile did not show a significant effect on the chosen UIV or curve magnitude correction. Level of Evidence: Level III: this is a retrospective case-control study.

Statement of purpose Visual and autonomic system disturbances are common sequelae of concussion. Clinical concussion diagnosis currently relies on subjective assessments such as symptom questions such as the Post-Concussion Symptom Inventory (PCSI). Quantification of visual and autonomic dysfunction could provide an objective method of acute diagnosis and subacute identification of ongoing injury. Methods/Approach We collected objective eye tracking data from three cohorts ages 12–17 years: healthy controls (n=105, mean age: 15.3, 56.2% female), concussed cases seen within 28 days of injury (acute, n=125, mean days since injury:12.5, mean age: 15.4, 46.4% female) and concussed cases seen within 29–90 days of injury (sub-acute, n=94, mean days since injury: 53.6, mean age: 15.4, 70.2% female). We compared self-reported symptoms and eye tracking metrics across groups using a series of chi-square analyses and one-way analysis of variance, with Tukey’s range test for post-hoc testing. Bonferroni corrections were used to account for multiple comparisons. Results Controls reported significantly lower PCSI scores (mean ± SD: 6.0 ± 9.1) than acute cases (31.2 ± 24.7, p Conclusion Measures of pupil diameter were greater for acute and sub-acute cases compared to healthy controls, suggesting autonomic dysfunction post-injury. No other metrics related to eye movement were discriminatory in this cohort, likely due to the heterogeneity of concussion. Significance These findings support the quantification of visual and autonomic dysfunction as objective markers of pediatric concussion.

Background Cancer-related cognitive decline (CRCD) has been linked to apolipoprotein E (APOE) gene ε4 polymorphisms. APOE ε4 polymorphisms are also the strongest genetic risk for late-onset Alzheimer disease (AD), whereas ε2 polymorphisms protect against AD. However, the effects of ε2 polymorphisms on CRCD have not been evaluated. Methods We evaluated nonmetastatic breast cancer survivors (n = 427) and matched noncancer controls (n = 407) ages 60-98 years assessed presystemic therapy from August 2010 to December 2017 with annual follow-up to 24 months. Neuropsychological assessment measured attention, processing speed, executive function, and learning and memory. Linear mixed-effects models tested the effects of having an ε2 allele (vs none) on longitudinal cognitive domain z scores by treatment group (chemotherapy with or without hormonal therapy, hormonal therapy, and control) controlling for covariates; participants with ε2/ε4 genotype were excluded. Sensitivity analyses examined effects of other covariates and any ε4 positivity. Results There was an interaction with genotype for attention, processing speed, and executive functioning domain scores (Beta = 0.32, 95% confidence interval = 0.00 to 0.65); the chemotherapy group with an ε2 allele had higher scores at baseline and maintained higher scores over time compared with those without an ε2 allele, and this protective effect was not seen for other groups. There was no effect of ε2 on learning and memory domain scores. Conclusions APOE ε2 polymorphisms may protect against CRCD in older breast cancer survivors receiving chemotherapy. With replication, this information could be useful for survivorship care and informing future studies of possible links to AD and defining mechanisms of protection.

ObjectivesInforming research participants of the results of studies in which they took part is viewed as an ethical imperative. However, there is little guidance in the literature about how to do this. The Fluoxetine Or Control Under Supervision trial randomised 3127 patients with a recent acute stroke to 6 months of fluoxetine or placebo and was published in the Lancet on 5 December 2018. The trial team decided to inform the participants of the results at exactly the same time as the Lancet publication, and also whether they had been allocated fluoxetine or placebo. In this report, we describe how we informed participants of the results.DesignIn the 6-month and 12-month follow-up questionnaires, we invited participants to provide an email address if they wished to be informed of the results of the trial. We re-opened our trial telephone helpline between 5 December 2018 and 31 March 2019.SettingUK stroke services.Participants3127 participants were randomised. 2847 returned 6-month follow-up forms and 2703 returned 12-month follow-up forms; the remaining participants had died (380), withdrawn consent or did not respond.ResultsOf those returning follow-up questionnaires, a total of 1845 email addresses were provided and a further 50 people requested results to be sent by post. Results were sent to all email and postal addresses provided; 309 emails were returned unrecognised. Seventeen people replied, of whom three called the helpline and the rest responded by email.ConclusionIt is feasible to disseminate results of large trials to research participants, though only around 60% of those randomised wanted to receive the results. The system we developed was efficient and required very little resource, and could be replicated by trialists in the future.Trial registration numberISRCTN83290762; Post-results.

Menopause is associated with increasing cognitive complaints and older women are at increased risk of developing Alzheimer disease compared to men. However, there is difficulty in early markers of risk using objective performance measures. We investigated the impact of subjective cognitive complaints on the cortical structure in a sample of younger postmenopausal women.Data for this cross-sectional study were drawn from the baseline visit of a longer double-blind study examining estrogen-cholinergic interactions in normal postmenopausal women. Structural Magnetic Resonance Imaging was acquired on 44 women, aged 50-60 years and gray-matter volume was defined by voxel-based morphometry. Subjective measures of cognitive complaints and postmenopausal symptoms were obtained as well as tests of verbal episodic and working memory performance.Increased levels of cognitive complaints were associated with lower gray-matter volume in the right medial temporal lobe (r = -0.445, P 0.002, R = 0.2). Increased depressive symptoms and somatic complaints were also related to increased cognitive complaints and smaller medial temporal volumes but did not mediate the effect of cognitive complaints. In contrast, there was no association between performance on the memory tasks and subjective cognitive ratings, or medial temporal lobe volume.The findings of the present study indicate that the level of reported cognitive complaints in postmenopausal women may be associated with reduced gray-matter volume which may be associated with cortical changes that may increase risk of future cognitive decline. : Video Summary:http://links.lww.com/MENO/A626.Video Summary:http://links.lww.com/MENO/A626.

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.

Introduction Cervicofacial infection (CFI) is a common presentation to the Oral and Maxillofacial (OMFS) department and accounts for significant emergency activity. The current study aims to understand the aetiology, management and clinical features of patients hospitalised with CFI. Methods Our study included all patients admitted for management of CFI from May to October 2017 at 25 OMFS units across 17 UK regions. Data were collected prospectively and included age, comorbidities, prior treatment received, markers of sepsis and presenting clinical features. Results One thousand and two (1002) admissions were recorded; 546 (54.5%) were male. Median age was 34 years (1-94 years). The most common presenting complaints were trismus (46%) and dysphagia (27%). Airway compromise was present in 1.7% of cases. Odontogenic infection accounted for 822/1002 (82%) admissions. Of those with an infection of odontogenic origin, 453/822 (55.1%) had received previous treatment. Two-thirds of those who had received treatment were managed by antibiotics alone (300/453, 66.2%) Patients met criteria for sepsis in 437/1002 (43.6%) of CFI, and in 374/822 (45.5%) of odontogenic infections. Conclusion This is the largest study worldwide of patients requiring inpatient management for CFI. Infection due to odontogenic origin is the most frequent reason for admission and nearly half do not seek treatment before presentation. Patients with CFI often present late in their disease and frequently meet criteria for sepsis, requiring timely and aggressive treatment to ensure optimum outcomes. Trismus is an emerging dominant feature with all the implications related to the anaesthetic management of these patients. Knowledge of these factors has implications for the referrer, triage, the emergency department, the anaesthetic team and members of the OMFS team.

Background: There are little data to explain why the surgical subspecialty of orthopaedic surgery struggles with improving the racial/ethnic composition of its workforce. The current work sought to determine what orthopaedic residency program directors and coordinators believe are the barriers to improving diversity at their own programs. Methods: Between November 17, 2018, and April 1, 2019, a 17-question survey was electronically distributed to the program directors and coordinators of 155 allopathic orthopaedic surgery residency programs. Seventy-five of 155 programs (48.4%) responded to the survey. A p-value of < 0.05 was used to determine statistical significance. Results: The most commonly stated barriers to increasing diversity within the orthopaedic surgery programs were the following: “We do not have enough minority faculty, which may deter the applicants” (69.3%), “We consistently rank minority applicants high but can never seem to match them” (56%), and “Not enough minorities are applying to our program” (54.7%). Programs with higher percentages of underrepresented minority (URM) faculty had higher percentages of URM residents (p = 0.001). Programs participating in the Nth Dimensions and/or Perry Initiative programs had a higher percentage of URM faculty as compared to the residency programs that did not participate in these programs (p = 0.004). URM residents represented 17.5% of all residents who resigned and/or were dismissed in the 10 years preceding the survey while also only representing 6% of all orthopaedic residents during the same time period. Conclusions: From the orthopaedic residency program perspective, the greatest perceived barrier to increasing the racial/ethnic diversity of residents in their program is their lack of URM faculty. Surveyed programs with more URM faculty had more URM residents, and programs participating in Nth Dimensions and/or Perry Initiative programs had a higher percentage of URM faculty.

IntroductionThe use and misuse of opioids by active service members has been examined in several studies, but little is known about their spouses’ opioid use. This study estimates the number of military spouses who received high-risk or long-term opioid prescriptions between 2010 and 2014, and addresses how the Military Health System can help prevent risky prescribing in order to improve military force readiness.Materials and MethodsThis study used data from the Millennium Cohort Family Study, a nationwide survey of 9,872 spouses of service members with 2 to 5 years of military service, augmented with information from the military’s Pharmacy Data Transaction Service about prescriptions for controlled drugs dispensed to these service members’ spouses. Our objectives were to estimate the prevalence of opioid prescribing indicative of long-term use (≥60 day supply or at least one extended-release opioid prescription in any 3-month period) and, separately, high-risk use (daily dosage of ≥90 morphine mg equivalent or total dosage of ≥8,190 morphine mg equivalent, or prescriptions from more than three pharmacies, or concurrent prescriptions). For each of these dependent variables, we conducted bivariate analyses and multiple logistic regression models using information about spouses’ physical health, sociodemographic characteristics, substance use behaviors, perceived social support, and stresses associated with military stress, among others. Informed consent, including consent to link survey responses to medical and personnel records, was obtained from all participants. The Naval Health Research Center’s Institutional Review Board and the Office of Management and Budget approved the study.ResultsSpouses were predominantly female (86%), had not served in the military themselves (79%), and were spouses of enlisted (91%) active duty (86%) service members. Almost half (47.6%) of spouses obtained at least one opioid prescription during the 2-year observation window, and 8.5% had received opioid prescriptions that posed risk to their health. About 7% met the criteria for receipt of high-risk opioid prescriptions, 3% obtained opioids from three or more pharmacies during a 3-month period, and 4% of spouses who received any opioids received both long-term and high-risk prescriptions. Adverse childhood experiences, physical pain, and lack of social support were associated with increased odds of obtaining high-risk opioid prescriptions.ConclusionsApproximately 48% of military spouses had used Military Health System insurance to fill at least one opioid prescription during the 2-year observation period. The Department of Defense has taken measures to minimize high-risk opioid prescribing, including passing prescribing guidelines in 2017, establishing the controlled drug management analysis reporting tool, establishing a pain management education and training program, and more. These efforts should continue to expand as reducing the numbers of service members and spouses at risk for adverse events may be effective in reducing opioid misuse and improve the overall health and safety of military spouses and thus, the readiness of the U.S. Armed Forces.

Timely assessment of patient-specific prognosis is critical to oncology care involving a shared decision-making approach, but clinical prognostic factors traditionally used in NSCLC have limitations. We examine a proteomic test to address these limitations.This study examines the prognostic performance of the VeriStrat blood-based proteomic test that measures the inflammatory disease state of patients with advanced NSCLC. A systematic literature review (SLR) was performed, yielding cohorts in which the hazard ratio (HR) was reported for overall survival (OS) of patients with VeriStrat Poor (VSPoor) test results versus VeriStrat Good (VSGood). A study-level meta-analysis of OS HRs was performed in subgroups defined by lines of therapy and treatment regimens.Twenty-four cohorts met SLR criteria. Meta-analyses in five subgroups (first-line platinum-based chemotherapy, second-line single-agent chemotherapy, first-line EGFR-tyrosine kinase inhibitor (TKI) therapy, and second- and higher-line TKI therapy, and best supportive care) resulted in statistically significant (Advanced NSCLC patients classified VSGood have significantly longer OS than those classified VSPoor. The summary effect size for OS HRs around 0.4-0.5 indicates that the expected median survival of those with a VSGood classification is approximately 2-2.5 times as long as those with VSPoor. The robust prognostic performance of the VeriStrat test across various lines of therapy and treatment regimens has clinical implications for treatment shared decision-making and potential for novel treatment strategies.

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.

Delineating age-related cortical trajectories in healthy individuals is critical given the association of cortical thickness with cognition and behaviour. Previous research has shown that deriving robust estimates of age-related brain morphometric changes requires large-scale studies. In response, we conducted a large-scale analysis of cortical thickness in 17,075 individuals aged 3-90 years by pooling data through the Lifespan Working group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium. We used fractional polynomial (FP) regression to characterize age-related trajectories in cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma (LMS) method. Inter-individual variability was estimated using meta-analysis and one-way analysis of variance. Overall, cortical thickness peaked in childhood and had a steep decrease during the first 2-3 decades of life; thereafter, it showed a gradual monotonic decrease which was steeper in men than in women particularly in middle-life. Notable exceptions to this general pattern were entorhinal, temporopolar and anterior cingulate cortices. Inter-individual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results reconcile uncertainties about age-related trajectories of cortical thickness; the centile values provide estimates of normative variance in cortical thickness, and may assist in detecting abnormal deviations in cortical thickness, and associated behavioural, cognitive and clinical outcomes.

Purpose School violence, frequently resulting in serious injury, is a major public health concern, and can make students afraid to go school. Few studies investigate the myriad factors that contribute to school violence. We are conducting a mixed-methods study of school assaults, including violence that happen on the way to or from school. Approach In an urban environment, this NIJ-funded study of 12-18 year-olds involves using a map-based interview of the path of their activities up to the time of assault, with case-crossover analyses to identify situation-specific risk factors. Recruitment sites include a Level I trauma center, health clinics, and community centers. Results With a goal of 200, 45 participants have been enrolledto date: 85% African American, 4% Hispanic. Injuries sustained were blunt trauma (42%), concussion (23%), and fracture (4%). 50% of the incidents were described as random violence, 35% as non-gang fight, and 8% as gang fight. 38% occurred inside school, 27% on school grounds, and 4% off site. None had been carrying a weapon at the time of the injury. Only 18% reported they knew how to acquire a gun, and 43% reported they would tell a teacher if a student had a gun at school whereas 57% reported they would not do so. Importantly, 65% of incidents were reported to police and of those, 80% of participants felt the police were helpful. However 50% of respondents felt the conflict was not resolved. 60% had a teacher highly invested in them and 65% reported a teacher expects them to attend college. Thematic results thus far suggest students were vulnerable at moments when guardianship was absent, which varied from location to location during the school day. Conclusions and Significance Understanding the context of the timing and nature of school-based assaults can inform opportunities for place-based interventions.

Supplemental Digital Content is available in the text., Objectives: SLC-0111 is an ureido-substituted benzenesulfonamide small molecule inhibitor of carbonic anhydrase IX. The objectives of this first-in-human Phase 1 study were to determine the safety and tolerability of SLC-0111 in patients with advanced solid tumors and to establish the recommended Phase 2 dose for future clinical investigations. Materials and Methods: Using a 3+3 design, dose escalation started at 500 mg oral daily dosing of SLC-0111 in cohort 1 and increased to 1000 and 2000 mg in cohorts 2 and 3. Drug-related adverse events (AEs) were monitored to determine safety and tolerability. Pharmacokinetic analyses assessed plasma concentrations of single and repeated doses of SLC-0111. RECIST 1.1 criteria were used to assess disease progression. Results: No dose-limiting toxicities were reported and patients dosed at ≤1000 mg exhibited fewer drug-related AEs ≥ grade 3 and fewer AEs such as nausea and vomiting, compared with the 2000-mg cohort. Forty-one percent of patients experienced dose interruptions or discontinuation and the majority (71%) of these occurred in the 2000-mg cohort. Mean Cmax and AUC(0-24) values for single doses were similar at the 1000-mg and 2000-mg dose levels. Mean Tmax and T1/2 values of SLC-0111 were similar after single and repeated dosing. Power-law analysis of Cmax and AUC0-24 showed that exposure to SLC-0111 was generally dose proportional. No objective responses were observed, but stable disease >24 weeks was observed in 2 patients. Conclusions: SLC-0111 was safe in patients with previously treated, advanced solid tumors. The safety and pharmacokinetic data support 1000 mg/d as the recommended phase 2 dose for SLC-0111.