Hemispheric Cerebral Oximetry Monitoring During Pediatric Seizure Activity in a Pediatric Emergency Department.

BACKGROUND: Sustained neuronal activity during seizures causes cellular perturbations, alterations in cerebral physiology, and potentially neurological injury, a neurological emergency. With variable clinical manifestations of seizures, frequent failure of seizure recognition by providers in pediatric and developmentally challenged patients can increase seizure complications. Neuroresuscitation should include rapid cerebral physiology assessment for increased seizure recognition and optimal neurological outcomes. In neurological emergencies, cerebral oximetry has demonstrated its utility in altered cerebral physiology and a standard combat neurological assessment tool. During adult seizures, cerebral oximetry (regional cerebral oxygen saturation [rcSO2]) has been shown as a useful neurological assessment tool, but research is lacking in pediatric emergency department (PED) seizure patients. OBJECTIVE: The aim of this study was to identify trends in rcSO2 readings for patients presenting to the PED with seizure activity and in the postseizure state in order to evaluate usefulness of rcSO2 as a neurological assessment tool in pediatric seizure patients. METHODS: This was a PED observational case series comparing hemispheric rcSO2 readings in first-time clinically evident generalized and focal seizure patients to first-time postseizure patients with no PED seizures. RESULTS: Generalized or focal seizure (n = 185) hemispheric rcSO2 revealed significant differences compared with nonseizure and controls' rcSO2 readings (n = 115) (P < 0.0001). Generalized and focal seizure rcSO2's were either less than 60% or greater than 80% compared with nonseizure rcSO2 (P < 0.0001). Ipsilateral focal seizure rcSO2 correlated to seizure side (P < 0.0001) and was less than the contralateral rcSO2 (P < 0.0001), with interhemispheric rcSO2 discordance greater than 16 (P < 0.0001). Seizure to preseizure rcSO2 discordance was as follows: generalized 15.2, focal: left 19.8, right 20.3 (P < 0.0001). CONCLUSIONS: Hemispheric during-seizure rcSO2 readings significantly correlated with generalized and focal seizures and reflected altered cerebral physiology. Ipsilateral focal seizure rcSO2 readings correlated to the focal side with wide interhemispheric rcSO2 discordance. All postseizure rcSO2 readings returned to preseizure readings, showing altered cerebral physiology resolution. Overall, in generalized or focal seizure, rcSO2 readings were less than 60% or greater than 80%, and in focal seizure, interhemispheric rcSO2 discordance was greater than 10. During seizures, hemispheric rcSO2 readings demonstrated its potential pediatric seizure utility. Utilizing rcSO2 readings related to seizure activity could expedite pediatric and developmentally challenged patients' seizure recognition, cerebral assessment, and interventions especially in pharmacoresistant seizures.

Bioavailability testing of a newly developed clindamycin oral suspension in a pediatric porcine model.

Background: Clindamycin's bitter taste and odor is known to affect treatment adherence in children. Recently, a formulation of clindamycin HCl complexed with ion exchange resin IRP 69 was shown to mask the bitter taste. Because of the potential benefit of this formulation for children, a pilot study using a porcine model was conducted to evaluate its relative bioavailability. Methods: A randomized two-way crossover study design using six (n = 6) healthy male piglets 10-12 kg was used to evaluate the absorption profiles and pharmacokinetic parameters of clindamycin from the resinate complex formulation (Test) compared to a commercialized reference suspension. A dose of 15 mg/kg was administered orally by gastric gavage to each piglet followed by repeated blood sampling over 12 h. A wash-out period of 48 h occurred between treatments. Plasma concentration vs. time data was analyzed by non-compartmental analysis. Results: The mean relative bioavailability of clindamycin from the resinate formulation was 78.8%. A two-tailed, paired Student t test yielded a p < 0.05 for AUC∞ and Tmax parameters. A two one-sided test (TOST) suggested a difference in AUC∞ and Cmax for the Test formulation compared to the reference formulation according to the FDA's criteria for bioequivalence. Conclusion: The bioavailability of clindamycin from this novel oral formulation supports continued evaluation of the drug in humans for potential pediatric applications.

Blood Viral Load in Symptomatic Congenital Cytomegalovirus Infection.

BACKGROUND: Viral loads (VLs) frequently are followed during treatment of symptomatic congenital cytomegalovirus disease, but their predictive value is unclear. METHODS: Post hoc analysis of 2 antiviral studies was performed. Seventy-three subjects were treated for 6 weeks and 47 subjects were treated for 6 months. Whole blood VL was determined by real-time polymerase chain reaction before and during therapy. RESULTS: Higher baseline VL was associated with central nervous system involvement (3.82 log, range 1-5.65 vs 3.32 log, range 1-5.36; P = .001), thrombocytopenia (3.68 log, range 1-5.65 vs 3.43 log, range 1-5.36; P = .03), and transaminitis at presentation (3.73 log, range 1-5.60 vs 3.39 log, range 1-5.65; P = .009), but with overlap in the amount of virus detected between groups. In subjects treated for 6 months, lower VL at presentation correlated with better hearing outcomes at 12 months, but VL breakpoints predictive of hearing loss were not identified. Sustained viral suppression during 6 months of therapy correlated with better hearing outcomes at 6, 12, and 24 months (P = .01, P = .0007, P = .04), but a majority without viral suppression still had improved hearing. CONCLUSIONS: In infants with symptomatic congenital cytomegalovirus disease, higher whole blood VL before initiation of antiviral therapy has no clinically meaningful predictive value for long-term outcomes.

An Adaptable Pediatrics Faculty Mentoring Model.

An effective faculty mentoring program (FMP) is 1 approach that academic departments can use to promote professional fulfillment, faculty retention, and mitigate the risks of faculty burnout. Mentoring has both direct benefits for junior faculty mentees as they navigate the academic promotion process with their mentors, in addition to broader departmental and institutional benefits, with regard to recruitment, retention, and academic productivity. We describe a successful FMP model that has been adapted for use in 6 other pediatrics departments, summarizing the key personnel, mentoring process, and program evaluation methods. Important lessons learned and a generalizable mentoring "model" are provided. Program evaluation indicates a positive effect for the FMP on enhanced faculty self-efficacy, job satisfaction, and career development. The importance of communication, oversight, feedback, accountability, and valuing all faculty members is emphasized. Strategies to promote faculty engagement and the critical role of departmental leadership in prioritizing mentorship are discussed. The success of academic medical departments is inextricably linked to its commitment to the career development of individual faculty members at all levels and in all academic pathways. With our findings, we support the positive impact of a formal FMP in promoting enhanced self-efficacy and career satisfaction, which directly benefits the department and institution through enhanced productivity, retention, successful promotion, and overall professional fulfillment.

Effects of Auditory Patterns on Judged Displacements of an Occluded Moving Object.

Using displays in which a moving disk disappeared behind an occluder, we examined whether an accompanying auditory rhythm influenced the perceived displacement of the disk during occlusion. We manipulated a baseline rhythm, comprising a relatively fast alternation of equal sound and pause durations. We had two different manipulations to create auditory sequences with a slower rhythm: either the pause durations or the sound durations were increased. In the trial, a disk moved at a constant speed, and at a certain point moved behind an occluder during which an auditory rhythm was played. Participants were instructed to track the occluded disk, and judge the expected position of the disk at the moment that the auditory rhythm ended by touching the judged position on a touch screen. We investigated the influence of the auditory rhythm, i.e., ratio of sound to pause duration, and the influence of auditory density, i.e., the number of sound onsets per time unit, on the judged distance. The results showed that the temporal characteristics affected the spatial judgments. Overall, we found that in the current paradigm relatively slow rhythms led to shorter judged distance as compared to relatively fast rhythms for both pause and sound variations. There was no main effect of auditory density on the judged distance of an expected visual event. That is, whereas the speed of the auditory rhythm appears crucial, the number of sound onsets per time unit as such, i.e., the auditory density, appears a much weaker factor.

Salmonella Infection After Craniotomy.

Salmonella is an uncommon cause of meningitis, especially after neurosurgery. Here, we present a case of Salmonella meningitis after craniotomy, likely due to physical contact with a snake after surgery, with contiguous spread from the patient's hand to her wound. The purpose of this report is to serve as a reminder that patients undergoing neurosurgery should avoid contact with pets, including snakes and other reptiles, in the postoperative period and practice good hand hygiene.

Variation in Tularemia Clinical Manifestations-Arkansas, 2009-2013.

BACKGROUND: Francisella tularensis, although naturally occurring in Arkansas, is also a Tier 1 select agent and potential bioterrorism threat. As such, tularemia is nationally notifiable and mandatorily reported to the Arkansas Department of Health. We examined demographic and clinical characteristics among reported cases and outcomes to improve understanding of the epidemiology of tularemia in Arkansas. METHODS: Surveillance records on all tularemia cases investigated during 2009-2013 were reviewed. RESULTS: The analytic dataset was assembled from 284 tularemia reports, yielding 138 probable and confirmed tularemia cases during 2009-2013. Arthropod bite was identified in 77% of cases. Of 7 recognized tularemia manifestations, the typhoidal form was reported in 47% of cases, approximately double the proportion of the more classic manifestation, lymphadenopathy. Overall, 41% of patients were hospitalized; 3% died. The typhoidal form appeared to be more severe, accounting for the majority of sepsis and meningitis cases, hospitalizations, and deaths. Among patients with available antibiotic data, 88% received doxycycline and 12% received gentamicin. CONCLUSIONS: Contrary to expectation, lymphadenopathy was not the most common manifestation observed in our registry. Instead, our patients were more likely to report only generalized typhoidal symptoms. Using lymphadenopathy as a primary symptom to initiate tularemia testing may be an insensitive diagnostic strategy and result in unrecognized cases. In endemic areas such as Arkansas, suspicion of tularemia should be high, especially during tick season. Outreach to clinicians describing the full range of presenting symptoms may help address misperceptions about tularemia.

An Explanation for the Role of the Amygdala in Aesthetic Judgments.

It has been proposed that the top-down guidance of feature-based attention is the basis for the involvement of the amygdala in various tasks requiring emotional decision-making (Jacobs et al., 2012a). Aesthetic judgments are correlated with particular visual features and can be considered emotional in nature (Jacobs et al., 2016). Moreover, we have previously shown that various aesthetic judgments result in observers preferentially attending to different visual features (Jacobs et al., 2010). Here, we argue that-together-this explains why the amygdalae become active during aesthetic judgments of visual materials. We discuss potential implications and predictions of this theory that can be tested experimentally.

Association of Medical School Pediatric Department Chairs Principles of Lifelong Learning in Pediatric Medicine.

Pediatric general and subspecialty care requires continuous effort to maintain knowledge and competencies in clinical practice. Equally important are efforts by investigators and educators to maintain knowledge and competencies in the conduct of research and training. The Association of Medical School Pediatric Department Chairs initiated a survey in July 2015 to define principles of lifelong learning in pediatric medicine and determine the approaches and strategies used by chairs to assess knowledge and competence across the care, research, and teaching missions. A total of 101 of 142 chairs (71%) completed the survey. Six of 7 proposed principles were endorsed by 84% to 96% of Association of Medical School Pediatric Department Chairs members. The focus areas included individual accountability, individually relevant activities, use of evidence-based guidelines/national standards, gaining cognitive expertise, learning as a continuous effort, affordability, and focus on individual understanding. The chairs endorsed a requirement for evidence of lifelong learning, competence, and compliance by all faculty members in clinical (n = 89 [88%]), research (n = 63 [62%]), and educational (n = 85 [84%]) practice. The survey identified the strategies to assess lifelong learning and faculty competence and compliance in clinical, research, and educational roles. Across missions, chairs endorsed an expectation for individual responsibility supplemented by formal evaluation practices and institutional and regulatory office oversight. While chairs endorsed an important role for the American Board of Pediatrics in assessing and verifying lifelong learning, knowledge, and competence in general and specialty certification, most (n = 91 [90%]) endorsed a need to revise current board requirements to better emphasize closing gaps in knowledge and using approaches that are evidence-based. This study provides the perspectives of pediatric department chairs on principles for lifelong learning and strategies and approaches used to assess faculty competence and commitment to lifelong learning across missions.

Aesthetics by Numbers: Links between Perceived Texture Qualities and Computed Visual Texture Properties.

Our world is filled with texture. For the human visual system, this is an important source of information for assessing environmental and material properties. Indeed-and presumably for this reason-the human visual system has regions dedicated to processing textures. Despite their abundance and apparent relevance, only recently the relationships between texture features and high-level judgments have captured the interest of mainstream science, despite long-standing indications for such relationships. In this study, we explore such relationships, as these might be used to predict perceived texture qualities. This is relevant, not only from a psychological/neuroscience perspective, but also for more applied fields such as design, architecture, and the visual arts. In two separate experiments, observers judged various qualities of visual textures such as beauty, roughness, naturalness, elegance, and complexity. Based on factor analysis, we find that in both experiments, ~75% of the variability in the judgments could be explained by a two-dimensional space, with axes that are closely aligned to the beauty and roughness judgments. That a two-dimensional judgment space suffices to capture most of the variability in the perceived texture qualities suggests that observers use a relatively limited set of internal scales on which to base various judgments, including aesthetic ones. Finally, for both of these judgments, we determined the relationship with a large number of texture features computed for each of the texture stimuli. We find that the presence of lower spatial frequencies, oblique orientations, higher intensity variation, higher saturation, and redness correlates with higher beauty ratings. Features that captured image intensity and uniformity correlated with roughness ratings. Therefore, a number of computational texture features are predictive of these judgments. This suggests that perceived texture qualities-including the aesthetic appreciation-are sufficiently universal to be predicted-with reasonable accuracy-based on the computed feature content of the textures.

Liking versus Complexity: Decomposing the Inverted U-curve.

The relationship between liking and stimulus complexity is commonly reported to follow an inverted U-curve. However, large individual differences among complexity preferences of participants have frequently been observed since the earliest studies on the topic. The common use of across-participant analysis methods that ignore these large individual differences in aesthetic preferences gives an impression of high agreement between individuals. In this study, we collected ratings of liking and perceived complexity from 30 participants for a set of digitally generated grayscale images. In addition, we calculated an objective measure of complexity for each image. Our results reveal that the inverted U-curve relationship between liking and stimulus complexity comes about as the combination of different individual liking functions. Specifically, after automatically clustering the participants based on their liking ratings, we determined that one group of participants in our sample had increasingly lower liking ratings for increasingly more complex stimuli, while a second group of participants had increasingly higher liking ratings for increasingly more complex stimuli. Based on our findings, we call for a focus on the individual differences in aesthetic preferences, adoption of alternative analysis methods that would account for these differences and a re-evaluation of established rules of human aesthetic preferences.

Pharmacokinetics, Safety and Tolerability of Single Oral or Intravenous Administration of 200 mg Tedizolid Phosphate in Adolescents.

BACKGROUND: Tedizolid is a novel oxazolidinone antibacterial US FDA approved for treatment of acute bacterial skin and skin structure infections in adults. This study assessed the pharmacokinetics, safety and tolerability of tedizolid phosphate in adolescents (12-17 years old) after administration of a single intravenous (IV) or oral dose. METHODS: In this multicenter, open-label study, a single IV infusion (N = 10) or oral dose (N = 10) of 200 mg tedizolid phosphate was administered to adolescents already receiving antibacterial treatment for presumed or documented infection. Blood and urine samples were collected predose and over 24 hours. RESULTS: Tedizolid pharmacokinetics was generally similar after IV or oral administration of 200 mg tedizolid phosphate. Mean (standard deviation) half-life values were similar for oral and IV routes, 8.3 (2.0) and 6.6 (0.7) hours, respectively. Absolute oral bioavailability of tedizolid (90% confidence interval) was 88.8% (70.4%-112.1%). Geometric mean ratio (90% confidence interval) of area under the concentration-time curve values for adolescents relative to values previously reported for adults after 200 mg of single-dose IV or oral administration were 0.847 (0.736-0.975). Tedizolid was well tolerated. CONCLUSIONS: Overall pharmacokinetics of tedizolid was similar after administration of a single oral or IV 200 mg dose, and bioavailability was high. Exposure profiles were similar to those in adults. With clinical outcomes based on area under the concentration-time curve/minimum inhibitory concentration and current susceptibility of Gram-positive pathogens, results suggest that the 200 mg daily regimen of tedizolid phosphate can be extended to adolescents for clinical trials, and that dose adjustment may not be required when switching routes.

A Randomized, Double-Blind, Placebo-Controlled Trial of Pleconaril for the Treatment of Neonates With Enterovirus Sepsis.

BACKGROUND: Neonatal enterovirus sepsis has high mortality. Antiviral therapy is not available. METHODS: Neonates with suspected enterovirus sepsis (hepatitis, coagulopathy, and/or myocarditis) with onset at ≤15 days of life were randomized 2:1 to receive oral pleconaril or placebo for 7 days. Serial virologic (oropharynx, rectum, urine, serum), clinical, pharmacokinetic, and safety evaluations were performed. RESULTS: Sixty-one subjects were enrolled (43 treatment, 18 placebo), of whom 43 were confirmed enterovirus infected (31 treatment, 12 placebo). There was no difference in day 5 oropharyngeal culture positivity (primary endpoint; 0% in both groups). However, enterovirus-infected subjects in the treatment group became culture negative from all anatomic sites combined faster than placebo group subjects (median 4.0 versus 7.0 days, P = .08), and fewer subjects in the treatment group remained polymerase chain reaction (PCR)-positive from the oropharynx when last sampled (23% versus 58%, P = .02; median, 14.0 days). By intent to treat, 10/43 (23%) subjects in the treatment group and 8/18 (44%) in the placebo group died (P = .02 for 2-month survival difference); among enterovirus-confirmed subjects, 7/31 (23%) in the treatment group died versus 5/12 (42%) in the placebo group (P = .26). All pleconaril recipients attained concentrations greater than the IC90 after the first study day, but 38% were less than the IC90 during the first day of treatment. One subject in the treatment group and three in the placebo group had treatment-related adverse events. CONCLUSIONS: Shorter times to culture and PCR negativity and greater survival among pleconaril recipients support potential efficacy and warrant further evaluation.

The neural signature of the Fraser illusion: an explorative EEG study on Fraser-like displays.

We studied neural correlates accompanying the Fraser spiral illusion. The Fraser spiral illusion consists of twisted cords superimposed on a patchwork background arranged in concentric circles, which is typically perceived as a spiral. We tested four displays: the Fraser spiral illusion and three variants derived from it by orthogonally combining featural properties. In our stimuli, the shape of the cords comprised either concentric circles or a single spiral. The cords themselves consisted of black and white lines in parallel to the contour of the cords (i.e., parallel cords), or oblique line elements (i.e., twisted cords). The displays with twisted cords successfully induced illusory percepts, i.e., circles looked like spirals (the Fraser spiral illusion) and spirals looked like circles (i.e., a "reverse Fraser illusion"). We compared the event-related potentials in a Stimulus (Circle, Spiral) × Percept (Circle, Spiral) design. A significant main effect of Stimulus was found at the posterior scalp in an early component (P220-280) and a significant main effect of Percept was found over the anterior scalp in a later component (P350-450). Although the EEG data suggest stimulus-based processing in the posterior area in an early time window and percept-based processing in the later time window, an overall clear-cut stimulus-percept segregation was not found due to additional interaction effects. Instead, the data, especially in the later time window in the anterior area, point at differential processing for the condition comprising circle shapes but spiral percepts (i.e., the Fraser illusion).

Valganciclovir for symptomatic congenital cytomegalovirus disease.

BACKGROUND: The treatment of symptomatic congenital cytomegalovirus (CMV) disease with intravenous ganciclovir for 6 weeks has been shown to improve audiologic outcomes at 6 months, but the benefits wane over time. METHODS: We conducted a randomized, placebo-controlled trial of valganciclovir therapy in neonates with symptomatic congenital CMV disease, comparing 6 months of therapy with 6 weeks of therapy. The primary end point was the change in hearing in the better ear ("best-ear" hearing) from baseline to 6 months. Secondary end points included the change in hearing from baseline to follow-up at 12 and 24 months and neurodevelopmental outcomes, with each end point adjusted for central nervous system involvement at baseline. RESULTS: A total of 96 neonates underwent randomization, of whom 86 had follow-up data at 6 months that could be evaluated. Best-ear hearing at 6 months was similar in the 6-month group and the 6-week group (2 and 3 participants, respectively, had improvement; 36 and 37 had no change; and 5 and 3 had worsening; P=0.41). Total-ear hearing (hearing in one or both ears that could be evaluated) was more likely to be improved or to remain normal at 12 months in the 6-month group than in the 6-week group (73% vs. 57%, P=0.01). The benefit in total-ear hearing was maintained at 24 months (77% vs. 64%, P=0.04). At 24 months, the 6-month group, as compared with the 6-week group, had better neurodevelopmental scores on the Bayley Scales of Infant and Toddler Development, third edition, on the language-composite component (P=0.004) and on the receptive-communication scale (P=0.003). Grade 3 or 4 neutropenia occurred in 19% of the participants during the first 6 weeks. During the next 4.5 months of the study, grade 3 or 4 neutropenia occurred in 21% of the participants in the 6-month group and in 27% of those in the 6-week group (P=0.64). CONCLUSIONS: Treating symptomatic congenital CMV disease with valganciclovir for 6 months, as compared with 6 weeks, did not improve hearing in the short term but appeared to improve hearing and developmental outcomes modestly in the longer term. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00466817.).

Single-dose pharmacokinetics of daptomycin in pediatric patients 3-24 months of age.

BACKGROUND: Daptomycin is approved for treatment of complicated skin/skin structure infections and Staphylococcus aureus bloodstream infections (bacteremia) in adults. This study was undertaken to determine the pharmacokinetics of daptomycin in pediatric patients 3-24 months of age with proven/suspected bacterial infection. METHODS: In this phase 1, multicenter, open-label, noncomparative pharmacokinetic and safety study, patients were enrolled in 3 age groups: 3-6, 7-12 and 13-24 months. Intravenous daptomycin (single dose) was infused over 30 minutes at 6 mg/kg in subjects 13-24 months of age and at 4 mg/kg in the younger groups. Blood was collected for analysis of daptomycin concentrations. RESULTS: Twenty-four subjects received daptomycin. Daptomycin exposures (area under the curve0-∞) in children 3-6 and 7-12 months of age receiving 4 mg/kg were similar (215 and 219 µg·h/mL, respectively). Children 13-24 months of age receiving a higher dose, 6 mg/kg, had higher exposures (282 µg·h/mL). Mean maximum plasma concentrations in the age groups were 38.7, 37.1 and 67.0 µg/mL, respectively. Daptomycin exposures based on mg/kg dosing were lower than previously reported for older children and adults, likely because of increased clearance and volume of distribution and decreased apparent elimination half-life. Single-dose daptomycin 4 and 6 mg/kg was well tolerated and was not associated with clinical or laboratory adverse events. CONCLUSIONS: To match known clinically and microbiologically effective exposures in adults, infants require higher mg/kg daptomycin doses. Daptomycin safety and efficacy have not been established in pediatric patients. Pediatric clinical trials are ongoing.

The representation of material categories in the brain.

Using textures mapped onto virtual nonsense objects, it has recently been shown that early visual cortex plays an important role in processing material properties. Here, we examined brain activation to photographs of materials, consisting of wood, stone, metal and fabric surfaces. These photographs were close-ups in the sense that the materials filled the image. In the first experiment, observers categorized the material in each image (i.e., wood, stone, metal, or fabric), while in an fMRI-scanner. We predicted the assigned material category using the obtained voxel patterns using a linear classifier. Region-of-interest and whole-brain analyses demonstrated material coding in the early visual regions, with lower accuracies for more anterior regions. There was little evidence for material coding in other brain regions. In the second experiment, we used an adaptation paradigm to reveal additional brain areas involved in the perception of material categories. Participants viewed images of wood, stone, metal, and fabric, presented in blocks with images of either different material categories (no adaptation) or images of different samples from the same material category (material adaptation). To measure baseline activation, blocks with the same material sample were presented (baseline adaptation). Material adaptation effects were found mainly in the parahippocampal gyrus, in agreement with fMRI-studies of texture perception. Our findings suggest that the parahippocampal gyrus, early visual cortex, and possibly the supramarginal gyrus are involved in the perception of material categories, but in different ways. The different outcomes from the two studies are likely due to inherent differences between the two paradigms. A third experiment suggested, based on anatomical overlap between activations, that spatial frequency information is important for within-category material discrimination.