Association of prepregnancy body mass index and gestational weight gain on severity of optic nerve hypoplasia.

BACKGROUND: Optic nerve hypoplasia (ONH) is a birth defect of unknown etiology and a leading cause of visual impairment in developed countries. Recent studies suggest that factors of deprivation and exposures of poor nutritional status, such as lower gestational weight gain (GWG), may be associated with increased risk of ONH. The present study describes the prenatal features of mothers of ONH cases, including prepregnancy BMI and GWG, and the associations with clinical features of disease severity. METHODS: Retrospective study of prenatal records for cases of ONH enrolled in a research registry. Prepregnancy BMI and GWG were compared to maternal characteristics and clinical findings of ONH severity including bilaterality, hypopituitarism, and neuroradiographic abnormalities. RESULTS: Compared to population-based normative data of births in the United States, mothers of ONH cases (n = 55) were younger (23.3 vs. 25.8 years; p = 0.03), with higher incidence of inadequate GWG (34.0% vs. 20.4%; p = 0.03) predominantly in the first and second trimesters. The presence of major brain malformations was associated with younger maternal age (21.6 [IQR 19.4, 24.7] vs. 24.9 years [IQR 22.1, 28.5] [p = 0.02]), primiparity (44.1% vs. 13.3%; p = 0.05) and decreased prepregnancy BMI (20.9 kg/m2 [19, 22.5] vs. 25.5 kg/m2 [21.3, 28.2]; p < 0.01). CONCLUSION: Decreased prepregnancy BMI and inadequate GWG correlated with clinical features of ONH severity, specifically bilateral disease and presence of major brain malformations.

Anticoagulation practices associated with bleeding and thrombosis in pediatric extracorporeal membrane oxygenation; a multi-center secondary analysis.

To determine associations between anticoagulation practices and bleeding and thrombosis during pediatric extracorporeal membrane oxygenation (ECMO), we performed a secondary analysis of prospectively collected data which included 481 children (<19 years), between January 2012 and September 2014. The primary outcome was bleeding or thrombotic events. Bleeding events included a blood product transfusion >80 ml/kg on any day, pulmonary hemorrhage, or intracranial bleeding, Thrombotic events included pulmonary emboli, intracranial clot, limb ischemia, cardiac clot, and arterial cannula or entire circuit change. Bleeding occurred in 42% of patients. Five percent of subjects thrombosed, of which 89% also bled. Daily bleeding odds were independently associated with day prior activated clotting time (ACT) (OR 1.03, 95% CI= 1.00, 1.05, p=0.047) and fibrinogen levels (OR 0.90, 95% CI 0.84, 0.96, p <0.001). Thrombosis odds decreased with increased day prior heparin dose (OR 0.88, 95% CI 0.81, 0.97, p=0.006). Lower ACT values and increased fibrinogen levels may be considered to decrease the odds of bleeding. Use of this single measure, however, may not be sufficient alone to guide optimal anticoagulation practice during ECMO.

Impact of Expanding Telephonic Codes in a State Medicaid Program During COVID-19.

Background: The recent pandemic caused by the 2019 novel coronavirus (COVID-19) resulted in declaration of a national emergency (NE) in March 2020. The Centers for Medicare and Medicaid Services quickly responded with temporary expansion of telehealth coverage policies. Aim: To determine the impact of implementing a temporary telephonic code set in a state Medicaid population by comparing the utilization patterns of telehealth claims before and after a NE announcement. Methods: This was a retrospective cohort study conducted with the Arizona Medicaid program, the Arizona Health Care Cost Containment System (AHCCCS). Data include telehealth claims submitted to AHCCCS between January and May 2020 by contracted managed care organizations. Results: Approximately 2.3 million telehealth claims were analyzed in this study. Utilization of the audio-visual (A/V) modality increased 1,610% and telephonic visits increased 408% compared with pre-NE. Compared with pre-NE, three provider type groups increased their utilization of telephonic visits from 1.8% to 50.8% as a result of the temporary telephonic set post-NE. Rural counties had higher rates of telephonic modality adoption, whereas urban counties adopted the A/V modality more readily. Ten telephonic codes constituted 87% of all telehealth claims, with the majority of those codes used for behavioral health and established office visit types. Conclusion: The telephonic modality was adopted more frequently in rural areas and the A/V modality in urban areas. There were several new provider types utilizing telehealth as a result of the temporary telephonic code set implementation.

Activated clotting time in inpatient diagnostic and interventional settings.

Monitoring for the anticoagulant effect of unfractionated (UFH) at the point of care using activated clotting time in real time is vital where risk of thrombosis is high. Although monitoring UFH effect is a routine and important task, changing from one ACT instrument type or technology to another must be preceded by a clinical and statistical evaluation to determine the suitability and repeatability and establish normal and treatable ranges of this newer instrument. In this multi-center prospective evaluation we tested 1236 paired ACT+ samples, and 463 paired ACT-LR samples (1699 total) from enrolled study subjects. Clinical settings included CVOR cardiopulmonary bypass, at the beside in extracorporeal life support (ELS), the Cardiac Catheterization Lab (CCL) during diagnostic studies and percutaneous coronary interventions (PCI), interventional radiology procedures and EP interventions. This study found more consistent clinical performance from the GEM Hemochron 100 as compared to the current clinical model, the Hemochron Signature Elite. The bias of GEM Hemochron 100 for ACT+ and ACT-LR was greatest in the setting of the CVOR where ACT levels were high. ACT-LR measurements by the GEM Hemochron 100 were comparable to the SE when performed in settings of CCL, ECM, EP and ICU. Results obtained for both ACT-LR and ACT+ in all clinical settings in this study using the GEM Hemochron 100 are as accurate and more repeatable as those with the current clinically available Signature Elite.

Reuniting Long Lost Cousins: a Novel Curriculum in Imaging Informatics for Clinical Informatics Fellows.

We developed a curriculum of imaging informatics for clinical informatics fellows. While imaging informatics and clinical informatics are related fields, they have distinct bodies of knowledge. The aim of this curriculum is to prepare clinical informatics fellows for questions regarding imaging informatics on the clinical informatics board certification examination, prepare fellows to handle issues and requests involving imaging informatics in their future roles as clinical informaticists, and develop sufficient knowledge and skills in order to interface with imaging and radiology domain experts. We mapped ACGME core competencies for clinical informatics and the clinical informatics skills and attributes to topics covered in this curriculum. Topics covered included orders vs. encounter-based workflow, understanding imaging informatics operations and the differences between an IT department leading digital image management and the radiology department, clinical decision support for radiology, procuring and integrating new modalities into a PACS system, troubleshooting slow application performance in a PACS environment, imaging sharing, artificial intelligence (AI) in imaging including AI bias, validation of models within home institution and regulatory issues, and structured reporting vs. Natural Language Processing to mine radiology report data. These topics were covered in interactive didactic sessions as well as a journal club. Future work will expand to include hands-on learning and a formal evaluation of this curriculum with current fellows and recent graduates.

Elucidating symptoms of COVID-19 illness in the Arizona CoVHORT: a longitudinal cohort study.

OBJECTIVE: To elucidate the symptoms of laboratory-confirmed COVID-19 cases as compared with laboratory-confirmed negative individuals and to the untested general population among all participants who reported symptoms within a large prospective cohort study. SETTING AND DESIGN: This work was conducted within the framework of the Arizona CoVHORT, a longitudinal prospective cohort study conducted among Arizona residents. PARTICIPANTS: Eligible participants were any individual living in Arizona and were recruited from across Arizona via COVID-19 case investigations, participation in testing studies and a postcard mailing effort. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was a comparison of the type and frequency of symptoms between COVID-19-positive cases, tested but negative individuals and the general untested population who reported experiencing symptoms consistent with COVID-19. RESULTS: Of the 1335 laboratory-confirmed COVID-19 cases, 180 (13.5%) reported having no symptoms. Of those that did report symptoms, the most commonly reported were fatigue (82.2%), headache (74.6%), aches, pains or sore muscles (66.3%), loss of taste or smell (62.8) and cough (61.9%). In adjusted logistic regression models, COVID-19-positive participants were more likely than negative participants to experience loss of taste and smell (OR 12.1; 95% CI 9.6 to 15.2), bone or nerve pain (OR 3.0; 95% CI 2.2 to 4.1), headache (OR 2.6; 95% CI 2.2 to 3.2), nausea (OR 2.4; 95% CI 1.9 to 3.1) or diarrhoea (OR 2.1; 95% CI 1.7 to 2.6). Fatigue (82.9) and headache (74.9) had the highest sensitivities among symptoms, while loss of taste or smell (87.2) and bone or nerve pain (92.9) had the high specificities among significant symptoms associated with COVID-19. CONCLUSION: When comparing confirmed COVID-19 cases with either confirmed negative or untested participants, the pattern of symptoms that discriminates SARS-CoV-2 infection from those arising from other potential circulating pathogens may differ from general reports of symptoms among cases alone.

Consequences of COVID-19 on adolescents in Arizona: A longitudinal study protocol.

Introduction: The long-term impact of COVID-19 is unknown. We developed a 5-year prospective cohort study designed to generate actionable community-informed research about the consequences of COVID-19 on adolescents ages 12-17 years in Arizona. Methods: The study has two primary outcomes: 1) acute and long-term outcomes of COVID-19 illness and 2) symptoms of depression and anxiety. Data is collected using an online survey with plans to integrate qualitative data collection methods. The survey is administered at baseline, 4, and 8 months in year one, and annually in years two through five. This study is informed by Intersectionality Theory, which considers the diverse identities adolescents have that are self and socially defined and the influence they have collectively and simultaneously. To this end, a sample of variables collected is race/ethnicity, language usage, generational status, co-occurring health conditions, and gender. Additional measures capture experiences in social contexts such as home (parent employment, food, and housing security), school (remote learning, type of school), and society (racism). Results: Findings are not presented because the manuscript is a protocol designed to describe the procedure instead of report results. Discussion: The unique contributions of the study is its focus on COVID-19 the illness and COVID-19 the socially experienced pandemic and the impact of both on adolescents.

Repeated measurements of ERGs and VEPs using chloral hydrate sedation and propofol anesthesia in young children.

PURPOSE: Sedation with chloral hydrate or anesthesia using propofol allow ocular examination and testing in young children, but these drugs may affect electrophysiologic recordings. We compared the flash and pattern ERGs and VEPs recorded with each drug in a cohort of young children enrolled in a prospective study of optic nerve hypoplasia (ONH) syndrome. METHODS: ERGs and VEPs to light-adapted, standard, full-field flashes, to standard and steady-state pattern-reversal (PR) were recorded with cycloplegia in 9 participants. Age range at the first session, with chloral hydrate was 8-23 mo; at the second session with propofol it was 20-29 mo. Examiners masked to the drug and clinical conditions measured the waveforms for longitudinal, paired comparisons between the sessions. RESULTS: Flash ERG amplitudes did not differ between sessions; peak times were longer at the second session (propofol) by clinically insignificant amounts (< 2 ms, p = 0.002). Standard PERGs had larger amplitudes and later peaks in the second session (propofol) than with chloral hydrate (P50 2.9 vs 4.7 µV, p = 0.016 and 43 vs 52 ms, p < 0.001; N95 4.0 vs 6.1 µV, p = 0.003 and 91 vs 98.5 ms p = 0.034.). These differences were present for those with an interval of  > 10 mo between sessions (n = 5, 10 eyes) but not for those with a shorter inter-test interval (< 8 mo, p > 0.05, n = 4). Magnitudes of the steady-state PERGs did not differ between tests but the waveforms had earlier peaks at the second test with propofol. Flash VEP waveforms were present in 10/18 eyes and showed 72% agreement for recordability between sessions. Standard pattern VEPs were recordable in only a few eyes in this cohort with ONH. CONCLUSIONS: Light-adapted flash ERG waveforms were generally similar with chloral hydrate and with propofol. Larger PERGs with later peaks, found in the second session (propofol) could reflect maturation of the PERG generators, as the differences found were associated with a greater age difference between the sessions, but we do not rule out that small differences in the waveforms may be drug-related. There are insufficient VEP data from these children with ONH to identify drug-related or maturational effects on VEPs.

Design of the Arizona CoVHORT: A Population-Based COVID-19 Cohort.

This study is a prospective, population-based cohort of individuals with a history of SARS-CoV-2 infection and those without past infection through multiple recruitment sources. The main study goal is to track health status over time, within the diverse populations of Arizona and to identify the long-term consequences of COVID-19 on health and well-being. A total of 2,881 study participants (16.2% with a confirmed SARS-CoV-2 infection) have been enrolled as of December 22, 2020, with a target enrollment of 10,000 participants and a planned follow-up of at least 2 years. This manuscript describes a scalable study design that utilizes a wide range of recruitment sources, leveraging electronic data collection to capture and link longitudinal participant data on the current and emerging issues associated with the COVID-19 pandemic. The cohort is built within a collaborative infrastructure that includes new and established partnerships with multiple stakeholders, including the state's public universities, local health departments, tribes, and tribal organizations. Challenges remain for ensuring recruitment of diverse participants and participant retention, although the electronic data management system and timing of participant contact can help to mitigate these problems.

Sex-Dependent Pathology in the HPA Axis at a Sub-acute Period After Experimental Traumatic Brain Injury.

Over 2.8 million traumatic brain injuries (TBIs) are reported in the United States annually, of which, over 75% are mild TBIs with diffuse axonal injury (DAI) as the primary pathology. TBI instigates a stress response that stimulates the hypothalamic-pituitary-adrenal (HPA) axis concurrently with DAI in brain regions responsible for feedback regulation. While the incidence of affective symptoms is high in both men and women, presentation is more prevalent and severe in women. Few studies have longitudinally evaluated the etiology underlying late-onset affective symptoms after mild TBI and even fewer have included females in the experimental design. In the experimental TBI model employed in this study, evidence of chronic HPA dysregulation has been reported at 2 months post-injury in male rats, with peak neuropathology in other regions of the brain at 7 days post-injury (DPI). We predicted that mechanisms leading to dysregulation of the HPA axis in male and female rats would be most evident at 7 DPI, the sub-acute time point. Young adult age-matched male and naturally cycling female Sprague Dawley rats were subjected to midline fluid percussion injury (mFPI) or sham surgery. Corticotropin releasing hormone, gliosis, and glucocorticoid receptor (GR) levels were evaluated in the hypothalamus and hippocampus, along with baseline plasma adrenocorticotropic hormone (ACTH) and adrenal gland weights. Microglial response in the paraventricular nucleus of the hypothalamus indicated mild neuroinflammation in males compared to sex-matched shams, but not females. Evidence of microglia activation in the dentate gyrus of the hippocampus was robust in both sexes compared with uninjured shams and there was evidence of a significant interaction between sex and injury regarding microglial cell count. GFAP intensity and astrocyte numbers increased as a function of injury, indicative of astrocytosis. GR protein levels were elevated 30% in the hippocampus of females in comparison to sex-matched shams. These data indicate sex-differences in sub-acute pathophysiology following DAI that precede late-onset HPA axis dysregulation. Further understanding of the etiology leading up to late-onset HPA axis dysregulation following DAI could identify targets to stabilize feedback, attenuate symptoms, and improve efficacy of rehabilitation and overall recovery.

Orbital MRI versus fundus photography in the diagnosis of optic nerve hypoplasia and prediction of vision.

INTRODUCTION: In patients with optic nerve hypoplasia (ONH), the visualisation of the optic disc can be challenging and the definitive diagnosis difficult to ascertain without fundus photography. The use of MRI for diagnosis has been reported as a diagnostic alternative with conflicting results. We retrospectively analysed a disease registry to determine the reliability of orbital MRI measurements of the optic nerve diameter to diagnose ONH, and the correlation with vision outcomes. MATERIALS AND METHODS: From a cohort of 140 patients with ONH (13% unilateral) that had reached age 5 years, we identified 43 subjects who had orbital MRI in addition to fundus photography performed prior to 2 years of age. We compared measurements of the optic nerve diameter from orbital MRI scans to the standard relative optic disc size (disc diameter/disc-macula (DD/DM) distance) by fundus photography. All patients had visual acuity tested at age 5 years. Spearman's correlation coefficient was used to determine the correlation of orbital MRI measurements and fundus photography with the diagnosis of ONH, and with vision outcomes. RESULTS: Relative disc size (DD/DM)<0.35 showed 100% sensitivity and 100% specificity for the diagnostic confirmation of ONH. The optic nerve diameter measurements by orbital MRI displayed a moderate correlation (rs=0.471; p<0.001) with DD/DM and moderate sensitivity for the diagnosis of ONH. Final visual acuity correlated well with DD/DM measurements by fundus photography (rs=-0.869; p<0.001) and moderately with optic nerve diameter by orbital MRI (rs=-0.635; p<0.001). DISCUSSION: Orbital optic nerve diameter from MRI scans has moderate reliability in diagnosing ONH and predicting vision outcomes. Fundus photography for measurements of the optic nerve size should remain the reference for diagnostic confirmation of ONH. These data further support the prognostic value of fundus photography for eventual vision outcomes in this population.

Development of the Pediatric Extracorporeal Membrane Oxygenation Prediction Model for Risk-Adjusting Mortality.

OBJECTIVES: To develop a prognostic model for predicting mortality at time of extracorporeal membrane oxygenation initiation for children which is important for determining center-specific risk-adjusted outcomes. DESIGN: Multivariable logistic regression using a large national cohort of pediatric extracorporeal membrane oxygenation patients. SETTING: The ICUs of the eight tertiary care children's hospitals of the Collaborative Pediatric Critical Care Research Network. PATIENTS: Five-hundred fourteen children (< 19 yr old), enrolled with an initial extracorporeal membrane oxygenation run for any indication between January 2012 and September 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 514 first extracorporeal membrane oxygenation runs were analyzed with an overall mortality of 45% (n = 232). Weighted logistic regression was used for model selection and internal validation was performed using cross validation. The variables included in the Pediatric Extracorporeal Membrane Oxygenation Prediction model were age (pre-term neonate, full-term neonate, infant, child, and adolescent), indication for extracorporeal membrane oxygenation (extracorporeal cardiopulmonary resuscitation, cardiac, or respiratory), meconium aspiration, congenital diaphragmatic hernia, documented blood stream infection, arterial blood pH, partial thromboplastin time, and international normalized ratio. The highest risk of mortality was associated with the presence of a documented blood stream infection (odds ratio, 5.26; CI, 1.90-14.57) followed by extracorporeal cardiopulmonary resuscitation (odds ratio, 4.36; CI, 2.23-8.51). The C-statistic was 0.75 (95% CI, 0.70-0.80). CONCLUSIONS: The Pediatric Extracorporeal Membrane Oxygenation Prediction model represents a model for predicting in-hospital mortality among children receiving extracorporeal membrane oxygenation support for any indication. Consequently, it holds promise as the first comprehensive pediatric extracorporeal membrane oxygenation risk stratification model which is important for benchmarking extracorporeal membrane oxygenation outcomes across many centers.

Altered speech with migraine attacks: A prospective, longitudinal study of episodic migraine without aura.

BACKGROUND AND OBJECTIVE: Some individuals with migraine report the presence of speech changes during their migraine attacks. The goal of this study was to compare objective features of speech during the migraine pre-attack, the migraine attack, and during the interictal period. METHODS: This was a prospective, longitudinal, observational study of adults with episodic migraine and healthy non-migraine controls. Participants provided speech samples three times per day using a speech elicitation tool included within a mobile app. Six complementary speech features that capture articulation and prosody were extracted from speech samples. Participants with migraine maintained a daily headache diary using the same app. A mixed effects model and t-tests were used to investigate differences in speech features between controls, the migraine pre-attack phase, the migraine attack, and the interictal period. RESULTS: In total, 56,767 speech samples were collected, including 43,102 from 15 individuals with migraine and 13,665 from matched healthy controls. Significant group-level differences in speech features were identified between those with migraine and healthy controls and within the migraine group during the pre-attack vs. attack vs. interictal periods (all p < .05). Most consistently, speech changes occurred in the speaking rate, articulation rate and precision, and phonatory duration. Within-subject analysis revealed that seven of 15 individuals with migraine showed significant change in at least one speech feature when comparing the migraine attack vs. interictal phase and four showed similar changes when comparing the pre-attack vs. interictal phases. CONCLUSIONS: Changes in speech occurred in almost half of the individuals during migraine attacks. Once confirmed in subsequent studies, speech changes could be considered a feature of the migraine attack.

Risk of hypoglycemia in youth with type 2 diabetes on insulin.

BACKGROUND: The objective of this study was to ascertain the risk of hypoglycemia among youth with type 2 diabetes (T2D) on insulin therapy. METHODS: Twenty-two youth with T2D on insulin therapy (M=12, F=10, age=14.4±4.0 years) were enrolled from a single pediatric endocrine practice. They were followed-up for 3 months with weekly phone calls and monthly in-person visits to review blood glucose logs and document any signs or symptoms of hypoglycemia (defined as finger stick glucose of ≤70 mg/dL). Episodes of hypoglycemia were categorized into five categories: severe, documented symptomatic, asymptomatic, probable symptomatic and relative hypoglycemia. In addition to examining the risk of hypoglycemia, the degree to which hypoglycemia was associated with patient demographics (e.g. age, gender and body mass index [BMI]) or clinical factors (i.e. duration of diabetes, duration of insulin treatment, glycemic control or insulin dose and regimen) was determined. RESULTS: Nine hypoglycemic events occurred during the study period in five patients with an incidence rate of nine events per 5.3 patient-years. Of the hypoglycemic events, five were symptomatic and four were asymptomatic. No severe hypoglycemic events occurred. Hypoglycemia was not associated with age, ethnicity, duration of insulin treatment, insulin dose or initial hemoglobin (HbA1c). However, a significant difference in BMI was noted, with T2D youth who experienced hypoglycemia having a lower BMI than those who did not experience hypoglycemia. CONCLUSIONS: The results of this study suggest that the risk of hypoglycemia in youth with T2D on insulin therapy is low.

Brain Malformations Do Not Predict Hypopituitarism in Young Children with Optic Nerve Hypoplasia.

BACKGROUND: Optic nerve hypoplasia (ONH), a leading cause of pediatric blindness, is associated with brain malformations and hypopituitarism in the constellation known as septo-optic dysplasia. Neuroimaging is used to anticipate hypopituitarism, but with unconfirmed reliability. We report prospective findings on the association of hypopituitarism with brain malformations. METHODS: Children (<24 months) with ONH (n = 146; 87% bilateral) underwent baseline MRI and annual examinations and hormonal testing. Hypopituitarism status at age 5 years was classified. RESULTS: A total of 74% had brain malformation(s). Hypopituitarism (69%) was not associated with brain malformations (p = 0.351); this persisted after adjusting for the laterality of ONH and the timing of MRI (padj = 0.869). No association was noted for absent septum pellucidum (38%; p = 0.073), corpus callosum abnormality (51%; p = 0.625), and major malformations (22%; p = 0.407). A malformation conferred a positive predictive value of 71% (95% CI: 62%, 80%), and a negative predictive value of 37% (95% CI: 22%, 54%). Overall, 10% (n = 15) of the cohort presented with a triad of absent septum pellucidum, corpus callosum abnormality, and other major malformation; only half (n = 8) of these had hypopituitarism. All 13 subjects with pituitary malformations manifested hypopituitarism, conferring predictive values of 100% (positive) and 34% (negative). CONCLUSIONS: Hypopituitarism and brain malformations are highly prevalent, but have unrelated associations with ONH. Brain MRI in infants and toddlers with ONH is an unreliable screen for hypopituitarism risk.

Predictive value of N95 waveforms of pattern electroretinograms (PERGs) in children with optic nerve hypoplasia (ONH).

PURPOSE: As part of a long-term, prospective study of prenatal and clinical risk factors for optic nerve hypoplasia (ONH) at Children's Hospital Los Angeles, pattern ERGs (PERGs) were evaluated for prognostic value using an automated objective and robust analytical method. METHODS: Participants were 33 children with ophthalmoscopically diagnosed ONH [disc diameter-to-disc macula ratio (DD/DM) less than 0.35 in one or both eyes on fundus photographs]. Using cycloplegia and chloral hydrate sedation in one session before 26 months of age, we recorded PERGs to checkerboard reversal using five check sizes. Participants were followed with clinical and psychometric testing until 5 years of age. PERGs were analysed using automated robust statistics based on magnitude-squared coherence and bootstrapping optimized to objectively quantify PERG recovery in the challenging recordings encountered in young patients. PERG measures in the fixating or better-seeing eyes were compared with visual outcome data. RESULTS: PERG recording was complete to at least three check sizes in all eyes and to all five sizes in 79%. Probability of recording a PERG that is significantly different from noise varied with check size from 73% for the largest checks to 30% for the smallest checks (p = 0.002); smaller waveforms were associated with earlier implicit times. The presence of significant PERGs in infancy is associated with better visual outcomes; the strongest association with visual outcome was for the threshold check size with a significant N95 component (ρ = 0.398, p = 0.02). CONCLUSIONS: Automated statistically robust signal-processing techniques reliably and objectively detect PERGs in young children with ONH and show that congenital deficits of retinal ganglion cells are associated with diminished or non-detectable PERGs. The later negativity, N95, was the best indicator of visual prognosis and was most useful to identify those with good visual outcomes (≤0.4 LogMAR). Although PERGs reflect function of the inner layers of the central retina, they lack the specificity required to determine prognosis reliably in individual cases.

Identifying an Oxygenation Index Threshold for Increased Mortality in Acute Respiratory Failure.

BACKGROUND: The objective of this work was to examine current oxygenation index (OI) data and outcomes using electronic medical record data to identify a specific OI value associated with mortality. METHODS: This study was a retrospective electronic medical record data review from the pediatric ICU of Phoenix Children's Hospital, with data mining for variables to calculate OIs on subjects age 1 month to 20 y mechanically ventilated > 24 h, excluding those with known intracardiac shunts or cyanotic heart disease. Age, length of hospital stay, duration of mechanical ventilation, and outcomes were also assessed. The Wilcoxon signed-rank test was used to compare continuous variables, receiver operating characteristic analysis was used in determining discriminant ability, and logistic regression was conducted to determine the odds ratio (OR) for risk of death with increasing OI. RESULTS: OI was calculated on 65 subjects, of whom 6 died (9%). The median maximum OI was 10 for all subjects, 17 for non-survivors, and 8 for survivors (P = .14 via Wilcoxon rank-sum test). ORs indicated a 2.4-fold increase in the odds of death (P = .09, 95% CI 0.9-6.6) for each increasing point in maximum OI. Mean OI OR revealed a 1.9-fold increase in the odds of death (P = .25, 95% CI 0.6-5.9). Receiver operating characteristic analysis indicated a higher discriminate ability for maximum OI (area under the curve = 0.68) than mean OI (area under the curve = 0.58). OI cut-points for mortality were established. Mortality was unchanged until maximum OI > 17, for which mortality nearly tripled at a value of 18% versus 6-7% for range 0-17. CONCLUSIONS: Limitations exist in obtaining serial OI values from current electronic medical records. Serial assessment of OI values may allow creation of alert values for increased mortality risk. Consideration of escalation of therapies for respiratory failure, such as high-frequency ventilation, inhaled nitric oxide, or extracorporeal membrane oxygenation may be warranted at lower OIs than historically reported.

Longitudinal changes in linguistic complexity among professional football players.

Reductions in spoken language complexity have been associated with the onset of various neurological disorders. The objective of this study is to analyze whether similar trends are found in professional football players who are at risk for chronic traumatic encephalopathy. We compare changes in linguistic complexity (as indexed by the type-to-token ratio and lexical density) measured from the interview transcripts of players in the National Football League (NFL) to those measured from interview transcripts of coaches and/or front-office NFL executives who have never played professional football. A multilevel mixed model analysis reveals that exposure to the high-impact sport (vs no exposure) was associated with an overall decline in language complexity scores over time. This trend persists even after controlling for age as a potential confound. The results set the stage for a prospective study to test the hypothesis that language complexity decline is a harbinger of chronic traumatic encephalopathy.

Factors Associated with Bleeding and Thrombosis in Children Receiving Extracorporeal Membrane Oxygenation.

RATIONALE: Extracorporeal membrane oxygenation (ECMO) is used for respiratory and cardiac failure in children but is complicated by bleeding and thrombosis. OBJECTIVES: (1) To measure the incidence of bleeding (blood loss requiring transfusion or intracranial hemorrhage) and thrombosis during ECMO support; (2) to identify factors associated with these complications; and (3) to determine the impact of these complications on patient outcome. METHODS: This was a prospective, observational cohort study in pediatric, cardiac, and neonatal intensive care units in eight hospitals, carried out from December 2012 to September 2014. MEASUREMENTS AND MAIN RESULTS: ECMO was used on 514 consecutive patients under age 19 years. Demographics, anticoagulation practices, severity of illness, circuitry components, bleeding, thrombotic events, and outcome were recorded. Survival was 54.9%. Bleeding occurred in 70.2%, including intracranial hemorrhage in 16%, and was independently associated with higher daily risk of mortality. Circuit component changes were required in 31.1%, and patient-related clots occurred in 12.8%. Laboratory sampling contributed to transfusion requirement in 56.6%, and was the sole reason for at least one transfusion in 42.2% of patients. Pump type was not associated with bleeding, thrombosis, hemolysis, or mortality. Hemolysis was predictive of subsequent thrombotic events. Neither hemolysis nor thrombotic events increased the risk of mortality. CONCLUSIONS: The incidences of bleeding and thrombosis are high during ECMO support. Laboratory sampling is a major contributor to transfusion during ECMO. Strategies to reduce the daily risk of bleeding and thrombosis, and different thresholds for transfusion, may be appropriate subjects of future trials to improve outcomes of children requiring this supportive therapy.

Gunshot wounds resulting in hospitalization in the United States: 2004-2013.

INTRODUCTION: The United States (US) leads all high income countries in gunshot wound (GSW) deaths. However, as a result of two decades of reduced federal support, study of GSW has been largely neglected. In this paper we describe the current state of GSW hospitalizations in the US using population-based data. PATIENTS AND METHODS: We conducted an observational study of patients hospitalized for GSW in the National (Nationwide) Inpatient Sample (NIS) 2004 -2013. Our primary outcome is mortality after admission and we model its associations with gender, race, age, intent, severity of injury and weapon type, as well as providing temporal trends in hospital charges. RESULTS: Each year approximately 30,000 patients are hospitalized for GSW, and 2500 die in hospital. Men are 9 times as likely to be hospitalized for GSW as women, but are less likely to die. Twice as many blacks are hospitalized for GSW as non-Hispanic whites. In-hospital mortality for blacks and non-Hispanic whites was similar when controlled for other factors. Most GSW (63%) are the result of assaults which overwhelmingly involve blacks; accidents are also common (23%) and more commonly involve non-Hispanic whites. Although suicide is much less common (8.3%), it accounts for 32% of all deaths; most of which are older non-Hispanic white males. Handguns are the most common weapon reported, and have the highest mortality rate (8.4%). During the study period, the annual rate of hospitalizations for GSW remained stable at 80 per 100,000 hospital admissions; median inflation-adjusted hospital charges have steadily increased by approximately 20% annually from $30,000 to $56,000 per hospitalization. The adjusted odds for mortality decreased over the study period. Although extensively reported, GSW inflicted by police and terrorists represent few hospitalizations and very few deaths. CONCLUSIONS: The preponderance GSW hospitalizations resulting from assaults on young black males and suicides among older non-Hispanic white males have continued unabated over the last decade with escalating costs. As with other widespread threats to the public wellbeing, federally funded research is required if effective interventions are to be developed.