Effects of inpatient rehabilitation after acute care on motor, neuropsychological and behavioral outcomes in children with severe traumatic brain injury.

PURPOSE: An observational study of children with severe traumatic brain injury (TBI) (Approaches and Decisions in Acute Pediatric TBI [ADAPT] Trial) demonstrated the benefits of inpatient rehabilitation on functional outcomes for those with more severely impaired consciousness when medically stable. We conducted a secondary analysis to assess whether using an inpatient rehabilitation or skilled nursing facility after acute hospitalization was associated with better motor, neuropsychological, and behavioral outcomes compared to receiving only non-inpatient rehabilitation among children with severe TBI. MATERIALS AND METHODS: We included 180 children who used an inpatient rehabilitation or skilled nursing facility and 74 children who only received non-inpatient rehabilitation from the ADAPT trial. At 12 months post-injury, children underwent tests of motor skills, intellectual functioning, verbal learning, memory, processing speed, and cognitive flexibility. Parents/guardians rated children's executive function and behaviors. We performed inverse probability weighting to adjust for potential confounders. RESULTS: No significant differences were found in any motor, neuropsychological, or behavioral measures between children receiving inpatient rehabilitation and children receiving only non-inpatient rehabilitation. CONCLUSIONS: Analyses of comprehensive outcomes did not show differences between children receiving inpatient rehabilitation and children receiving only non-inpatient rehabilitation, suggesting a need for more research on specific components of the rehabilitation process.

Our study showed no differences in motor, neuropsychological, or behavioral outcomes at 12 months after severe traumatic brain injury (TBI) between children using an inpatient rehabilitation or skilled nursing facility and children receiving only non-inpatient rehabilitation after acute hospitalization.Children surviving severe TBI should be evaluated for the need of inpatient and outpatient rehabilitation therapies at discharge from an acute care hospital.Children with rehabilitation requirements after severe TBI should be followed up periodically to ensure the continuity of care and reduce the gaps to the needed rehabilitation therapies.

Multi-modal MRI of hippocampal morphometry and connectivity after pediatric severe TBI.

This investigation explores memory performance using the California Verbal Learning Test in relation to morphometric and connectivity measures of the memory network in severe traumatic brain injury. Twenty-two adolescents with severe traumatic brain injury were recruited for multimodal MRI scanning 1-2 years post-injury at 13 participating sites. Analyses included hippocampal volume derived from anatomical T1-weighted imaging, fornix white matter microstructure from diffusion tensor imaging, and hippocampal resting-state functional magnetic resonance imaging connectivity as well as diffusion-based structural connectivity. A typically developing control cohort of forty-nine age-matched children also underwent scanning and neurocognitive assessment. Results showed hippocampus volume was decreased in traumatic brain injury with respect to controls. Further, hippocampal volume loss was associated with worse performance on memory and learning in traumatic brain injury subjects. Similarly, hippocampal fornix fractional anisotropy was reduced in traumatic brain injury with respect to controls, while decreased fractional anisotropy in the hippocampal fornix also was associated with worse performance on memory and learning in traumatic brain injury subjects. Additionally, reduced structural connectivity of left hippocampus to thalamus and calcarine sulcus was associated with memory and learning in traumatic brain injury subjects. Functional connectivity in the left hippocampal network was also associated with memory and learning in traumatic brain injury subjects. These regional findings from a multi-modal neuroimaging approach should not only be useful for gaining valuable insight into traumatic brain injury induced memory and learning disfunction, but may also be informative for monitoring injury progression, recovery, and for developing rehabilitation as well as therapy strategies.

Associations between postpartum pain type, pain intensity and opioid use in patients with and without opioid use disorder: a cross-sectional study.

BACKGROUND: Pain is a multidimensional construct. The purpose of this cross-sectional, single-centre study was to evaluate the relationship between postpartum pain type with pain intensity and opioid use in people with and without opioid use disorder (OUD). METHODS: Postpartum pain type was coded from McGill Pain Questionnaire and Patient-Reported Outcome Measurement Information System (PROMIS) inventories in people with or without OUD after childbirth in a 4-month period. The co-primary outcomes were pain intensity (0-10 scale) and total inpatient oxycodone (mg). Multivariable linear mixed-effects models assessed between- and within-person relationships for pain type (primary predictor) and outcomes. RESULTS: There were 44 522 unique pain scores and types from 2610 people. Pain types were associated with pain intensity (P<0.001). Between-person comparisons showed affective pain was associated with a small but higher total oxycodone dose (difference 1.04 mg compared with no affective pain, P<0.001). Among people with OUD, within-person comparisons showed that the presence of affective pain resulted in pain scores 1 point higher than when affective pain was not present (P=0.002); between-person comparisons showed that people with affective pain had pain scores 6 points higher (P=0.048). Within-person and between-person comparisons among OUD showed that nociceptive/neuropathic pain was associated with a higher total oxycodone dose (1.6 and 11.4 mg, respectively). CONCLUSIONS: Postpartum pain type was associated with pain intensity and opioid use. Further research is required to address the multiple dimensions of postpartum pain in people with and without OUD to improve treatment of postpartum pain.

Quantifying the risk of prosthetic joint infections after invasive dental procedures and the effect of antibiotic prophylaxis.

BACKGROUND: Dentists face the expectations of orthopedic surgeons and patients with prosthetic joints to provide antibiotic prophylaxis (AP) before invasive dental procedures (IDPs) to reduce the risk of late periprosthetic joint infections (LPJIs), despite the lack of evidence associating IDPs with LPJIs, lack of evidence of AP efficacy, risk of AP-related adverse reactions, and potential for promoting antibiotic resistance. The authors aimed to identify any association between IDPs and LPJIs and whether AP reduces LPJI incidence after IDPs. METHOD: The authors performed a case-crossover analysis comparing IDP incidence in the 3 months immediately before LPJI hospital admission (case period) with the preceding 12-month control period for all LPJI hospital admissions with commercial or Medicare supplemental or Medicaid health care coverage and linked dental and prescription benefits data. RESULTS: Overall, 2,344 LPJI hospital admissions with dental and prescription records (n = 1,160 commercial or Medicare supplemental and n = 1,184 Medicaid) were identified. Patients underwent 4,614 dental procedures in the 15 months before LPJI admission, including 1,821 IDPs (of which 18.3% had AP). Our analysis identified no significant positive association between IDPs and subsequent development of LPJIs and no significant effect of AP in reducing LPJIs. CONCLUSIONS: The authors identified no significant association between IDPs and LPJIs and no effect of AP cover of IDPs in reducing the risk of LPJIs. PRACTICAL IMPLICATIONS: In the absence of benefit, the continued use of AP poses an unnecessary risk to patients from adverse drug reactions and to society from the potential of AP to promote development of antibiotic resistance. Dental AP use to prevent LPJIs should, therefore, cease.

Understanding a Care Management System's Role in Influencing a Transitional-Aged Youth Program's Practice: Mixed Methods Study.

BACKGROUND: Extended foster care programs help prepare transitional-aged youth (TAY) to step into adulthood and live independent lives. Aspiranet, one of California's largest social service organizations, used a social care management solution (SCMS) to meet TAY's needs. OBJECTIVE: We aimed to investigate the impact of an SCMS, IBM Watson Care Manager (WCM), in transforming foster program service delivery and improving TAY outcomes. METHODS: We used a mixed methods study design by collecting primary data from stakeholders through semistructured interviews in 2021 and by pulling secondary data from annual reports, system use logs, and data repositories from 2014 to 2021. Thematic analysis based on grounded theory was used to analyze qualitative data using NVivo software. Descriptive analysis of aggregated outcome metrics in the quantitative data was performed and compared across 2 periods: pre-SCMS implementation (before October 31, 2016) and post-SCMS implementation (November 1, 2016, and March 31, 2021). RESULTS: In total, 6 Aspiranet employees (4 leaders and 2 life coaches) were interviewed, with a median time of 56 (IQR 53-67) minutes. The majority (5/6, 83%) were female, over 30 years of age (median 37, IQR 32-39) with a median of 6 (IQR 5-10) years of experience at Aspiranet and overall field experience of 10 (IQR 7-14) years. Most (4/6, 67%) participants rated their technological skills as expert. Thematic analysis of participants' interview transcripts yielded 24 subthemes that were grouped into 6 superordinate themes: study context, the impact of the new tool, key strengths, commonly used features, expectations with WCM, and limitations and recommendations. The tool met users' initial expectations of streamlining tasks and adopting essential functionalities. Median satisfaction scores around pre- and post-WCM workflow processes remained constant between 2 life coaches (3.25, IQR 2.5-4); however, among leaders, post-WCM scores (median 4, IQR 4-5) were higher than pre-WCM scores (median 3, IQR 3-3). Across the 2 study phases, Aspiranet served 1641 TAY having consistent population demographics (median age of 18, IQR 18-19 years; female: 903/1641, 55.03%; race and ethnicity: Hispanic or Latino: 621/1641, 37.84%; Black: 470/1641, 28.64%; White: 397/1641, 24.19%; Other: 153/1641, 9.32%). Between the pre- and post-WCM period, there was an increase in full-time school enrollment (359/531, 67.6% to 833/1110, 75.04%) and a reduction in part-time school enrollment (61/531, 11.5% to 91/1110, 8.2%). The median number of days spent in the foster care program remained the same (247, IQR 125-468 years); however, the number of incidents reported monthly per hundred youth showed a steady decline, even with an exponentially increasing number of enrolled youth and incidents. CONCLUSIONS: The SCMS for coordinating care and delivering tailored services to TAY streamlined Aspiranet's workflows and processes and positively impacted youth outcomes. Further enhancements are needed to better align with user and youth needs.

Effects of inpatient rehabilitation after acute care on functional and quality-of-life outcomes in children with severe traumatic brain injury.

OBJECTIVE: Few studies have assessed the effectiveness of the rehabilitation process in children surviving severe traumatic brain injury (TBI). We evaluated whether receiving inpatient rehabilitation after acute hospitalization was associated with better functional outcomes compared to receiving only non-inpatient rehabilitation in children with severe TBI and explored an effect modification for Glasgow Coma Scale (GCS) score at hospital discharge. METHODS: We included 254 children who received rehabilitation following severe TBI from a multinational observational study. The Pediatric Glasgow Outcome Scale - Extended (GOS-E Peds), parent/guardian-reported and child-reported Pediatric Quality of Life Inventory (PedsQL) at 12 months post-injury were assessed and described using summary statistics. Unadjusted and propensity score-weighted linear/ordinal logistic regression modeling were also performed. RESULTS: 180 children received inpatient rehabilitation and 74 children received only non-inpatient rehabilitation after acute hospitalization. Among children with a GCS<13 at discharge, those receiving inpatient rehabilitation had a more favorable GOS-E Peds score (OR = 0.12, p = 0.045). However, no such association was observed in children with a higher GCS. We found no differences in PedsQL scores between rehabilitation groups. CONCLUSIONS: Future studies are warranted to confirm the benefits of inpatient rehabilitation for children with more severely impaired consciousness when medically stable.

Magnetic Resonance Imaging Findings in Infants with Severe Traumatic Brain Injury and Associations with Abusive Head Trauma.

Young children with severe traumatic brain injury (TBI) have frequently been excluded from studies due to age and/or mechanism of injury. Magnetic resonance imaging (MRI) is now frequently being utilized to detect parenchymal injuries and early cerebral edema. We sought to assess MRI findings in infants with severe TBI, and to determine the association between specific MRI findings and mechanisms of injury, including abusive head trauma (AHT). MRI scans performed within the first 30 days after injury were collected and coded according to NIH/NINDS Common Data Elements (CDEs) for Neuroimaging in subjects age < 2 years old with severe TBI enrolled in the Approaches and Decisions in Acute Pediatric Traumatic Brain Injury Trial. Demographics and injury characteristics were analyzed. A total of 81 children were included from ADAPT sites with MRI scans. Median age was 0.77 years and 57% were male. Most common MRI finding was ischemia, present in 57/81 subjects (70%), in a median of 7 brain regions per subject. Contusion 46/81 (57%) and diffuse axonal injury (DAI) 36/81 (44.4%) subjects followed. Children were dichotomized based on likelihood of AHT with 43/81 subjects classified as AHT. Ischemia was found to be significantly associated with AHT (p = 0.001) and "inflicted" injury mechanism (p = 0.0003). In conclusion, the most common intracerebral injury seen on MRI of infants with severe TBI was ischemia, followed by contusion and DAI. Ischemia was associated with AHT, and ischemia affecting > 4 brain regions was predictive of AHT.

Comparative Effectiveness of Diversion of Cerebrospinal Fluid for Children With Severe Traumatic Brain Injury.

Importance: Diversion of cerebrospinal fluid (CSF) has been used for decades as a treatment for children with severe traumatic brain injury (TBI) and is recommended by evidenced-based guidelines. However, these recommendations are based on limited studies. Objective: To determine whether CSF diversion is associated with improved Glasgow Outcome Score-Extended for Pediatrics (GOS-EP) and decreased intracranial pressure (ICP) in children with severe TBI. Design, Setting, and Participants: This observational comparative effectiveness study was performed at 51 clinical centers that routinely care for children with severe TBI in 8 countries (US, United Kingdom, Spain, the Netherlands, Australia, New Zealand, South Africa, and India) from February 2014 to September 2017, with follow-up at 6 months after injury (final follow-up, October 22, 2021). Children with severe TBI were included if they had Glasgow Coma Scale (GCS) scores of 8 or lower, had intracranial pressure (ICP) monitor placed on-site, and were aged younger than 18 years. Children were excluded if they were pregnant or an ICP monitor was not placed at the study site. Consecutive children were screened and enrolled, data regarding treatments were collected, and at discharge, consent was obtained for outcomes testing. Propensity matching for pretreatment characteristics was performed to develop matched pairs for primary analysis. Data analyses were completed on April 18, 2022. Exposures: Clinical care followed local standards, including the use of CSF diversion (or not), with patients stratified at the time of ICP monitor placement (CSF group vs no CSF group). Main Outcomes and Measures: The primary outcome was GOS-EP at 6 months, while ICP was considered as a secondary outcome. CSF vs no CSF was treated as an intention-to-treat analysis, and a sensitivity analysis was performed for children who received delayed CSF diversion. Results: A total of 1000 children with TBI were enrolled, including 314 who received CSF diversion (mean [SD] age, 7.18 [5.45] years; 208 [66.2%] boys) and 686 who did not (mean [SD] age, 7.79 [5.33] years; 437 [63.7%] boys). The propensity-matched analysis included 98 pairs. In propensity score-matched analyses, there was no difference between groups in GOS-EP (median [IQR] difference, 0 [-3 to 1]; P = .08), but there was a decrease in overall ICP in the CSF group (mean [SD] difference, 3.97 [0.12] mm Hg; P < .001). Conclusions and Relevance: In this comparative effectiveness study, CSF diversion was not associated with improved outcome at 6 months after TBI, but a decrease in ICP was observed. Given the higher quality of evidence generated by this study, current evidence-based guidelines related to CSF diversion should be reconsidered.

Comparison of Intracranial Pressure Measurements Before and After Hypertonic Saline or Mannitol Treatment in Children With Severe Traumatic Brain Injury.

Importance: Hyperosmolar agents are cornerstone therapies for pediatric severe traumatic brain injury. Guideline recommendations for 3% hypertonic saline (HTS) are based on limited numbers of patients, and no study to date has supported a recommendation for mannitol. Objectives: To characterize current use of hyperosmolar agents in pediatric severe traumatic brain injury and assess whether HTS or mannitol is associated with greater decreases in intracranial pressure (ICP) and/or increases in cerebral perfusion pressure (CPP). Design, Setting, and Participants: In this comparative effectiveness research study, 1018 children were screened and 18 were excluded; 787 children received some form of hyperosmolar therapy during the ICP-directed phase of care, with 521 receiving a bolus. Three of these children were excluded because they had received only bolus administration of both HTS and mannitol in the same hour, leaving 518 children (at 44 clinical sites in 8 countries) for analysis. The study was conducted from February 1, 2014, to September 31, 2017, with follow-up for 1 week after injury. Final analysis was performed July 20, 2021. Interventions: Boluses of HTS and mannitol were administered. Main Outcomes and Measures: Data on ICP and CPP were collected before and after medication administration. Statistical methods included linear mixed models and corrections for potential confounding variables to compare the 2 treatments. Results: A total of 518 children (mean [SD] age, 7.6 [5.4] years; 336 [64.9%] male; 274 [52.9%] White) were included. Participants' mean (SD) Glasgow Coma Scale score was 5.2 (1.8). Bolus HTS was observed to decrease ICP and increase CPP (mean [SD] ICP, 1.03 [6.77] mm Hg; P < .001; mean [SD] CPP, 1.25 [12.47] mm Hg; P < .001), whereas mannitol was observed to increase CPP (mean [SD] CPP, 1.20 [11.43] mm Hg; P = .009). In the primary outcome, HTS was associated with a greater reduction in ICP compared with mannitol (unadjusted ß, -0.85; 95% CI, -1.53 to -0.19), but no association was seen after adjustments (adjusted ß, -0.53; 95% CI, -1.32 to 0.25; P = .18). No differences in CPP were observed. When ICP was greater than 20 mm Hg, greater than 25 mm Hg, or greater than 30 mm Hg, HTS outperformed mannitol for each threshold in observed ICP reduction (>20 mm Hg: unadjusted ß, -2.51; 95% CI, -3.86 to -1.15, P < .001; >25 mm Hg: unadjusted ß, -3.88; 95% CI, -5.69 to -2.06, P < .001; >30 mm Hg: unadjusted ß, -4.07; 95% CI, -6.35 to -1.79, P < .001), with results remaining significant for ICP greater than 25 mm Hg in adjusted analysis. Conclusions and Relevance: In this comparative effectiveness research study, bolus HTS was associated with lower ICP and higher CPP, whereas mannitol was associated only with higher CPP. After adjustment for confounders, both therapies showed no association with ICP and CPP. During ICP crises, HTS was associated with better performance than mannitol.

Differences in information accessed in a pharmacologic knowledge base using a conversational agent vs traditional search methods.

INTRODUCTION: Clinicians rely on pharmacologic knowledge bases to answer medication questions and avoid potential adverse drug events. In late 2018, an artificial intelligence-based conversational agent, Watson Assistant (WA), was made available to online subscribers to the pharmacologic knowledge base, Micromedex®. WA allows users to ask medication-related questions in natural language. This study evaluated search method-dependent differences in the frequency of information accessed by traditional methods (keyword search and heading navigation) vs conversational agent search. MATERIALS AND METHODS: We compared the proportion of information types accessed through the conversational agent to the proportion of analogous information types accessed by traditional methods during the first 6 months of 2020. RESULTS: Addition of the conversational agent allowed early adopters to access 22 different information types contained in the 'quick answers' portion of the knowledge base. These information types were accessed 117,550 times with WA during the study period, compared to 33,649,651 times using traditional search methods. The distribution across information types differed by method employed (c2 test, P < .0001). Single drug/dosing, FDA/non-FDA uses, adverse effects, and drug administration emerged as 4 of the top 5 information types accessed by either method. Intravenous compatibility was accessed more frequently using the conversational agent (7.7% vs. 0.6% for traditional methods), whereas dose adjustments were accessed more frequently via traditional methods (4.8% vs. 1.4% for WA). CONCLUSION: In a widely used pharmacologic knowledge base, information accessed through conversational agents versus traditional methods differed. User-centered studies are needed to understand these differences.

Characteristics Associated with the Use of an Inpatient Rehabilitation or Skilled Nursing Facility after Acute Care in Children with Severe Traumatic Brain Injury.

To characterize inpatient rehabilitation services for children with severe traumatic brain injury (TBI), we included 254 children, whose parents/guardians reported receipt of rehabilitation within a 12-month follow-up period, from a multinational observational study. Children discharged to an inpatient rehabilitation or skilled nursing facility after acute care were classified into the "inpatient rehabilitation" group, and children discharged home after acute care were classified into the "non-inpatient rehabilitation" group. Multivariable regression analyses determined the associations of sociodemographic and clinical characteristics with rehabilitation groups. Children receiving inpatient rehabilitation had a shorter length of acute hospitalization. Children from the UK were less likely to receive inpatient rehabilitation compared to children from the US. Future studies are warranted to extend current findings by identifying the reasons behind differential access to inpatient rehabilitation among children with severe TBI.

Biomarkers for Traumatic Brain Injury: Data Standards and Statistical Considerations.

Recent biomarker innovations hold potential for transforming diagnosis, prognostic modeling, and precision therapeutic targeting of traumatic brain injury (TBI). However, many biomarkers, including brain imaging, genomics, and proteomics, involve vast quantities of high-throughput and high-content data. Management, curation, analysis, and evidence synthesis of these data are not trivial tasks. In this review, we discuss data management concepts and statistical and data sharing strategies when dealing with biomarker data in the context of TBI research. We propose that application of biomarkers involves three distinct steps-discovery, evaluation, and evidence synthesis. First, complex/big data has to be reduced to useful data elements at the stage of biomarker discovery. Second, inferential statistical approaches must be applied to these biomarker data elements for assessment of biomarker clinical utility and validity. Last, synthesis of relevant research is required to support practice guidelines and enable health decisions informed by the highest quality, up-to-date evidence available. We focus our discussion around recent experiences from the International Traumatic Brain Injury Research (InTBIR) initiative, with a specific focus on four major clinical projects (Transforming Research and Clinical Knowledge in TBI, Collaborative European NeuroTrauma Effectiveness Research in TBI, Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe, and Approaches and Decisions in Acute Pediatric TBI Trial), which are currently enrolling subjects in North America and Europe. We discuss common data elements, data collection efforts, data-sharing opportunities, and challenges, as well as examine the statistical techniques required to realize successful adoption and use of biomarkers in the clinic as a foundation for precision medicine in TBI.

Use of magnetic resonance imaging in severe pediatric traumatic brain injury: assessment of current practice.

OBJECTIVE: There is no consensus on the optimal timing and specific brain MRI sequences in the evaluation and management of severe pediatric traumatic brain injury (TBI), and information on current practices is lacking. The authors performed a survey of MRI practices among sites participating in a multicenter study of severe pediatric TBI to provide information for designing future clinical trials using MRI to assess brain injury after severe pediatric TBI. METHODS: Information on current imaging practices and resources was collected from 27 institutions participating in the Approaches and Decisions after Pediatric TBI Trial. Multiple-choice questions addressed the percentage of patients with TBI who have MRI studies, timing of MRI, MRI sequences used to investigate TBI, as well as the magnetic field strength of MR scanners used at the participating institutions and use of standardized MRI protocols for imaging after severe pediatric TBI. RESULTS: Overall, the reported use of MRI in pediatric patients with severe TBI at participating sites was high, with 40% of sites indicating that they obtain MRI studies in > 95% of this patient population. Differences were observed in the frequency of MRI use between US and international sites, with the US sites obtaining MRI in a higher proportion of their pediatric patients with severe TBI (94% of US vs 44% of international sites reported MRI in at least 70% of patients with severe TBI). The reported timing and composition of MRI studies was highly variable across sites. Sixty percent of sites reported typically obtaining an MRI study within the first 7 days postinjury, with the remainder of responses distributed throughout the first 30-day postinjury period. Responses indicated that MRI sequences sensitive for diffuse axonal injury and ischemia are frequently obtained in patients with TBI, whereas perfusion imaging and spectroscopy techniques are less common. CONCLUSIONS: Results from this survey suggest that despite the lack of consensus or guidelines, MRI is commonly obtained during the acute clinical setting after severe pediatric TBI. The variation in MRI practices highlights the need for additional studies to determine the utility, optimal timing, and composition of clinical MRI studies after TBI. The information in this survey describes current clinical MRI practices in children with severe TBI and identifies important challenges and objectives that should be considered when designing future studies.

Presenting Characteristics Associated With Outcome in Children With Severe Traumatic Brain Injury: A Secondary Analysis From a Randomized, Controlled Trial of Therapeutic Hypothermia.

OBJECTIVES: To identify injury patterns and characteristics associated with severe traumatic brain injury course and outcome, within a well-characterized cohort, which may help guide new research and treatment initiatives. DESIGN: A secondary analysis of a phase 3, randomized, controlled trial that compared therapeutic hypothermia versus normothermia following severe traumatic brain injury in children. SETTING: Fifteen sites in the United States, Australia, and New Zealand. PATIENTS: Children (< 18 yr old) with severe traumatic brain injury. MEASUREMENTS AND MAIN RESULTS: Baseline, clinical, and CT characteristics of patients (n = 77) were examined for association with mortality and outcome, as measured by the Glasgow Outcome Scale-Extended Pediatric Revision 3 months after traumatic brain injury. Data are presented as odds ratios with 95% CIs. No demographic, clinical, or CT characteristic was associated with mortality in bivariate analysis. Characteristics associated with worse Glasgow Outcome Scale-Extended Pediatric Revision in bivariate analysis were two fixed pupils (14.17 [3.38-59.37]), abdominal Abbreviated Injury Severity score (2.03 [1.19-3.49]), and subarachnoid hemorrhage (3.36 [1.30-8.70]). Forward stepwise regression demonstrated that Abbreviated Injury Severity spine (3.48 [1.14-10.58]) and midline shift on CT (8.35 [1.05-66.59]) were significantly associated with mortality. Number of fixed pupils (one fixed pupil 3.47 [0.79-15.30]; two fixed pupils 13.61 [2.89-64.07]), hypoxia (5.22 [1.02-26.67]), and subarachnoid hemorrhage (3.01 [1.01-9.01]) were independently associated with worse Glasgow Outcome Scale-Extended Pediatric Revision following forward stepwise regression. CONCLUSIONS: Severe traumatic brain injury is a clinically heterogeneous disease that can be accompanied by a range of neurologic impairment and a variety of injury patterns at presentation. This secondary analysis of prospectively collected data identifies several characteristics associated with outcome among children with severe traumatic brain injury. Future, larger trials are needed to better characterize phenotypes within this population.

Phase I randomized clinical trial of N-acetylcysteine in combination with an adjuvant probenecid for treatment of severe traumatic brain injury in children.

BACKGROUND: There are no therapies shown to improve outcome after severe traumatic brain injury (TBI) in humans, a leading cause of morbidity and mortality. We sought to verify brain exposure of the systemically administered antioxidant N-acetylcysteine (NAC) and the synergistic adjuvant probenecid, and identify adverse effects of this drug combination after severe TBI in children. METHODS: IRB-approved, randomized, double-blind, placebo controlled Phase I study in children 2 to 18 years-of-age admitted to a Pediatric Intensive Care Unit after severe TBI (Glasgow Coma Scale [GCS] score ≤8) requiring an externalized ventricular drain for measurement of intracranial pressure (ICP). Patients were recruited from November 2011-August 2013. Fourteen patients (n = 7/group) were randomly assigned after obtaining informed consent to receive probenecid (25 mg/kg load, then 10 mg/kg/dose q6h×11 doses) and NAC (140 mg/kg load, then 70 mg/kg/dose q4h×17 doses), or placebos via naso/orogastric tube. Serum and CSF samples were drawn pre-bolus and 1-96 h after randomization and drug concentrations were measured via UPLC-MS/MS. Glasgow Outcome Scale (GOS) score was assessed at 3 months. RESULTS: There were no adverse events attributable to drug treatment. One patient in the placebo group was withdrawn due to adverse effects. In the treatment group, NAC concentrations ranged from 16,977.3±2,212.3 to 16,786.1±3,285.3 in serum and from 269.3±113.0 to 467.9±262.7 ng/mL in CSF, at 24 to 72 h post-bolus, respectively; and probenecid concentrations ranged from 75.4.3±10.0 to 52.9±25.8 in serum and 5.4±1.0 to 4.6±2.1 µg/mL in CSF, at 24 to 72 h post-bolus, respectively (mean±SEM). Temperature, mean arterial pressure, ICP, use of ICP-directed therapies, surveillance serum brain injury biomarkers, and GOS at 3 months were not different between groups. CONCLUSIONS: Treatment resulted in detectable concentrations of NAC and probenecid in CSF and was not associated with undesirable effects after TBI in children. TRIAL REGISTRATION: ClinicalTrials.gov NCT01322009.

Sleep-Wake Differences in Relative Regional Cerebral Metabolic Rate for Glucose among Patients with Insomnia Compared with Good Sleepers.

STUDY OBJECTIVES: The neurobiological mechanisms of insomnia may involve altered patterns of activation across sleep-wake states in brain regions associated with cognition, self-referential processes, affect, and sleep-wake promotion. The objective of this study was to compare relative regional cerebral metabolic rate for glucose (rCMRglc) in these brain regions across wake and nonrapid eye movement (NREM) sleep states in patients with primary insomnia (PI) and good sleeper controls (GS). METHODS: Participants included 44 PI and 40 GS matched for age (mean = 37 y old, range 21-60), sex, and race. We conducted [18F]fluoro-2-deoxy-D-glucose positron emission tomography scans in PI and GS during both morning wakefulness and NREM sleep at night. Repeated measures analysis of variance was used to test for group (PI vs. GS) by state (wake vs. NREM sleep) interactions in relative rCMRglc. RESULTS: Significant group-by-state interactions in relative rCMRglc were found in the precuneus/posterior cingulate cortex, left middle frontal gyrus, left inferior/superior parietal lobules, left lingual/fusiform/occipital gyri, and right lingual gyrus. All clusters were significant at Pcorrected < 0.05. CONCLUSIONS: Insomnia was characterized by regional alterations in relative glucose metabolism across NREM sleep and wakefulness. Significant group-by-state interactions in relative rCMRglc suggest that insomnia is associated with impaired disengagement of brain regions involved in cognition (left frontoparietal), self-referential processes (precuneus/posterior cingulate), and affect (left middle frontal, fusiform/lingual gyri) during NREM sleep, or alternatively, to impaired engagement of these regions during wakefulness.

Outcomes of Osteomyelitis in Patients Hospitalized With Diabetic Foot Infections.

BACKGROUND: This study was conducted to evaluate the outcomes of patients with diabetic foot osteomyelitis (DFO) compared to diabetic foot soft tissue infections (STIs). METHODS: 229 patients who were hospitalized with foot infections were retrospectively reviewed, identifying 155 patients with DFO and 74 patients with STI. Primary outcomes evaluated were the rates of amputations and length of hospital stay. DFO was confirmed by the presence of positive bone culture and/or histopathology. RESULTS: Patients with DFO had a 5.6 times higher likelihood of overall amputation (P < .0001), a 3.4 times higher likelihood of major amputation (P = .027) and a 4.2 times higher likelihood of minor amputation (P < .0001) compared to patients without DFO. Major amputation was performed in 16.7% patients diagnosed with DFO and 5.3% of patients diagnosed with STI. Patients with DFO complicated by Charcot neuroarthropathy had a 7 times higher likelihood of undergoing major amputation (odds ratio 6.78, 95% confidence interval 2.70-17.01, P < .0001). The mean hospital stay was 7 days in DFO and 6 days in patients with DFI (P = .0082). Patients with DFO had a higher erythrocyte sedimentation rate (85 vs 71, P = .02) than patients with STI, however the differences in C-reactive protein (13.4 vs 11.8, P = .29) were not significantly different. CONCLUSION: In this study of moderate and severe DFIs, the presence of osteomyelitis resulted in a higher likelihood of amputation and longer hospital stay. Readers should recognize that the findings of this study may not be applicable to less severe cases of DFO that can be effectively managed in an outpatient setting. LEVEL OF EVIDENCE: Level III, retrospective comparative case series.

Correlation of SF-36 and SF-12 Component Scores in Patients With Diabetic Foot Disease.

The assessment of patient outcomes is becoming increasingly important in all areas of medicine, including foot and ankle surgery. The Medical Outcomes Study Short Form 36-item (SF-36) is widely used as a generic measure of quality of life; however, patients often find answering 36 questions cumbersome. Consequently, the Short Form 12 (SF-12) was developed. We hypothesized that the agreement between the SF-12 and SF-36 component scores would be substantial in patients with diabetic foot disease. We retrospectively reviewed the data from 300 patients with diabetes mellitus (DM) and foot and ankle pathology who completed the SF-36 questionnaire. Of the 300 patients, 155 (51.7%) had problems directly related to complications of DM and 145 (48.3%) had routine foot complaints that were unrelated to complications of DM. The 12 questions of the SF-12 were abstracted from the SF-36. The overall median score for the SF-36 physical component summary was 34.70 compared with the overall SF-12 physical component summary of 36.75 (p = .04). The intraclass correlation coefficient was 0.93688. The overall median score for the SF-36 mental component summary was 52.40 compared with the overall SF-12 mental component summary of 51.25 (p = .34). The intraclass correlation coefficient was 0.95449. Substantial agreement was observed when comparing the component scores of the SF-12 and the SF-36. From our study results of 300 patients with DM, it appears that the SF-36 and SF-12 are comparable outcome instruments for use with patients with diabetic foot disease.

Low-Fidelity Haptic Simulation Versus Mental Imagery Training for Epidural Anesthesia Technical Achievement in Novice Anesthesiology Residents: A Randomized Comparative Study.

BACKGROUND: There are many teaching methods for epidural anesthesia skill acquisition. Previous work suggests that there is no difference in skill acquisition whether novice learners engage in low-fidelity (LF) versus high-fidelity haptic simulation for epidural anesthesia. No study, however, has compared the effect of LF haptic simulation for epidural anesthesia versus mental imagery (MI) training in which no physical practice is attempted. We tested the hypothesis that MI training is superior to LF haptic simulation training for epidural anesthesia skill acquisition. METHODS: Twenty Post-Graduate Year 2 (PGY-2) anesthesiology residents were tested at the beginning of the training year. After a didactic lecture on epidural anesthesia, they were randomized into 2 groups. Group LF had LF simulation training for epidural anesthesia using a previously described banana simulation technique. Group MI had guided, scripted MI training in which they initially were oriented to the epidural kit components and epidural anesthesia was described stepwise in detail, followed by individual mental rehearsal; no physical practice was undertaken. Each resident then individually performed epidural anesthesia on a partial-human task trainer on 3 consecutive occasions under the direct observation of skilled evaluators who were blinded to group assignment. Technical achievement was assessed with the use of a modified validated skills checklist. Scores (0-21) and duration to task completion (minutes) were recorded. A linear mixed-effects model analysis was performed to determine the differences in scores and duration between groups and over time. RESULTS: There was no statistical difference between the 2 groups for scores and duration to task completion. Both groups showed similarly significant increases (P = 0.0015) in scores over time (estimated mean score [SE]: group MI, 15.9 [0.55] to 17.4 [0.55] to 18.6 [0.55]; group LF, 16.2 [0.55] to 17.7 [0.55] to 18.9 [0.55]). Time to complete the procedure decreased similarly and significantly (P = 0.032) for both groups after the first attempt (estimated mean time [SE]: group MI, 16.0 [1.04] minutes to 13.7 [1.04] minutes to 13.3 [1.04] minutes; group LF: 15.8 [1.04] minutes to 13.4 [1.04] minutes to 13.1 [1.04] minutes). CONCLUSIONS: MI is not different from LF simulation training for epidural anesthesia skill acquisition. Education in epidural anesthesia with structured didactics and continual MI training may suffice to prepare novice learners before an attempt on human subjects.

Cerebral White Matter and Slow Gait: Contribution of Hyperintensities and Normal-appearing Parenchyma.

BACKGROUND: White matter hyperintensities (WMH), a common marker of cerebral small vessel disease, and lower microstructural integrity of normal-appearing white matter are associated with slower gait. How these cerebral measures interact in relation to slower gait is unknown. We assessed whether microstructural integrity of normal-appearing white matter, measured by fractional anisotropy (FA), moderates the association of higher WMH with slower gait. METHODS: WMH, FA, and gait speed were acquired for 265 community-dwelling older adults (average age = 82.9 years). RESULTS: The inverse association between WMH and gait was robust to adjustment for age, gender, muscle strength, obesity, stroke, and hypertension (fully adjusted model: ßs = -0.19, p = .001). The interaction between WMH and FA was significant; analyses stratified by FA showed that the inverse association between WMH and gait speed was significant only for those with low FA (FA < median, fully adjusted model: ßs = -0.28, p = .001). Voxel-based results were similar for participants with FA less than median, there was an inverse association between gait speed and WMH which extended throughout the white matter (genu and body of corpus callosum, anterior limb of internal capsule, corona radiata, and superior longitudinal and fronto-occipital fasciculus). In contrast, for participants with FA ≥ median, the association was limited to the genu of corpus callosum, the cingulum, and the inferior longitudinal fasciculus. CONCLUSIONS: Microstructural integrity is a moderating factor in the association between WMH and gait. Future studies should examine whether higher microstructural integrity represents a source of compensation in those with greater WMH burden to maintain function in late life.