High-Dose Midazolam for Pediatric Refractory Status Epilepticus: A Single-Center Retrospective Study.

OBJECTIVES: We sought to describe the prevalence of midazolam treatment failure in children with refractory status epilepticus (RSE) and define a threshold dose associated with diminishing frequency of seizure cessation. DESIGN: Single center retrospective cohort study. SETTING: Single-center, quaternary-care PICU. PATIENTS: Children younger than 18 years old admitted to the PICU from 2009 to 2018 who had RSE requiring a continuous midazolam infusion. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified individuals with RSE through a data analytics inquiry. Receiver operating characteristic (ROC) curve analysis and Youden's index were used to assess the midazolam dose threshold associated with the highest sensitivity and specificity in identifying seizure cessation. A logistic regression model was used to determine if there was an association between maximum midazolam dose and seizure cessation. Of the 45 patients who met inclusion criteria for this study, 27 (60%) had seizure cessation with a midazolam infusion, whereas 18 (40%) required an additional pentobarbital infusion for seizure cessation. There was an association between maximum midazolam dose and seizure cessation, with patients more likely to fail treatment when midazolam was administered at higher doses. The maximum midazolam dose displayed high area under the ROC curve value for seizure cessation, and the Youden's J index cut-off point was 525 µg/kg/hr. Treatment above this dose was associated with diminishing frequency of seizure cessation. The median time spent titrating midazolam above 500 µg/kg/hr for those patients who required pentobarbital for seizure cessation was 3.83 hours (interquartile range, 2.28-5.58 hr). CONCLUSIONS: In pediatric patients with RSE requiring high dose midazolam, considerable time is spent titrating doses in a range (above 500 µg/kg/hr) that is associated with diminishing frequency of seizure cessation.

Postoperative but not preoperative depression is associated with cognitive impairment after cardiac surgery: exploratory analysis of data from a randomized trial.

BACKGROUND: In this study we hypothesize that depression is associated with perioperative neurocognitive dysfunction and altered quality of life one month after surgery. METHODS: Data were obtained as part of a study evaluating cerebral autoregulation monitoring for targeting arterial pressure during cardiopulmonary bypass. Neuropsychological testing was performed before surgery and one month postoperatively. Testing included the Beck Depression Inventory, a depression symptoms questionnaire (0-63 scale), as well as anxiety and quality of life assessments. Depression was defined as a Beck Depression Inventory score > 13. RESULTS: Beck Depression data were available from 320 patients of whom cognitive domain endpoints were available from 88-98% at baseline and 69-79% after surgery. This range in end-points data was due to variability in the availability of each neuropsychological test results between patients. Depression was present in 50 (15.6%) patients before surgery and in 43 (13.4%) after surgery. Baseline depression was not associated with postoperative domain-specific neurocognitive function compared with non-depressed patients. Those with depression one month after surgery, though, had poorer performance on tests of attention (p = 0.017), memory (p = 0.049), verbal fluency (p = 0.010), processing speed (p = 0.017), and fine motor speed (p = 0.014). Postoperative neurocognitive dysfunction as a composite outcome occurred in 33.3% versus 14.5% of patients with and without postoperative depression (p = 0.040). Baseline depression was associated with higher anxiety and lower self-ratings on several quality of life domains, these measures were generally more adversely affected by depression one month after surgery. CONCLUSIONS: The results of this exploratory analysis suggests that preoperative depression is not associated with perioperative neurocognitive dysfunction, but depression after cardiac surgery may be associated with impairment in in several cognitive domains, a higher frequency of the composite neurocognitive outcome, and altered quality of life. TRIAL REGISTRATION: www. CLINICALTRIALS: gov, NCT00981474 (parent study).

Preoperative Anemia and Risk for Perioperative Neurocognitive Dysfunction in Cardiac Surgery Patients: A Retrospective Analysis.

OBJECTIVES: To evaluate whether there is a relationship between preoperative anemia and domain-specific cognitive performance in patients undergoing cardiac surgery. DESIGN: Retrospective analysis of data collected from a randomized study. SETTING: Tertiary care university hospital. PARTICIPANTS: A total of 436 patients age ≥55 years undergoing cardiac surgery. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Neuropsychological testing was performed before and one month after surgery, using a standard battery. Individual Z-scores calculated from the mean and standard deviation of tests at baseline were combined into domain-specific scores. Anemia (hemoglobin <130 g/L for men, <120 g/L for women) was present in 41% of patients. Preoperative anemia had little impact on preoperative cognition. There were no differences in the change in cognitive performance one month after surgery from baseline between patients with and without preoperative anemia. However, in a sensitivity analysis using multiple imputation for missing cognitive test scores, significant associations were observed between preoperative anemia and change in postoperative processing speed (p = 0.016), change in executive function (p = 0.049), and change in fine motor speed (p = 0.016). Nadir hemoglobin during cardiopulmonary bypass, which was lower in anemic than nonanemic patients, was associated with decrements in performance on tests of verbal fluency (p = 0.007), processing speed (p = 0.042), and executive function (p = 0.10) one month after surgery but not delayed neurocognitive recovery (p = 0.06). CONCLUSIONS: Preoperative anemia may be associated with impairment of selective cognitive domains after surgery. Any effect of preoperative anemia may have on cognition after surgery might be related to lower nadir hemoglobin during cardiopulmonary bypass.

The impact of a yoga-based physical therapy group for individuals with traumatic brain injury: results from a pilot study.

OBJECTIVE: To compare the impacts of yoga-based physical therapy versus a seated rest within the context of standard rehabilitation practice on sleep, heart rate variability (HRV), anxiety, and fatigue during acute traumatic brain injury (TBI) rehabilitation. METHODS: Eleven individuals participated in this crossover study involving the following interventions in a randomized order: group yoga-based physical therapy (YPT), conventional physical therapy (CPT), and group seated rest in a relaxing environment (SR). HRV and self-reported anxiety and fatigue were measured immediately before and after each group, and sleep after each condition and at baseline. Data was analyzed using generalized linear mixed models with repeated measures. RESULTS: The interaction between time and treatment was statistically significant (p = .0203). For the SR treatment, wake after sleep onset (WASO) rate was reduced from 14.99 to 10.60 (IRR = 0.71; p = .006). Time and treatment were not found to be statistically significantly associated with any of the secondary outcomes. CONCLUSION: Yoga-based physical therapy is feasible and safe in the inpatient rehabilitation setting following TBI. Sleep quality improved following the addition of a one-hour seated rest in a relaxing environment to a standard rehabilitation daily schedule, suggesting that structured rest time may be beneficial to sleep hygiene during inpatient rehabilitation following TBI. ClinicalTrials.Gov Registration Number: NCT03701594.

Depressive symptoms after stroke are associated with worse recovery.

OBJECTIVE: More studies are needed on how depressive symptoms in stroke patients can impact outcomes. We evaluated the relationship between depression symptom severity and motor outcomes in a cohort of patients with motor impairment from ischemic stroke. METHOD: We enrolled consecutive ischemic stroke patients without a clinical diagnosis of depression who presented to a single-center urban academic referral hospital. The Patient Health Questionnaire-9 (PHQ-9) scale was used to measure depression symptom severity at three months. Three assessments of motor function were collected at stroke onset and three months: Fugl-Meyer upper extremity (FM-UE), Motricity Index, and Action Research Arm Test (ARAT). We assessed the association between three-month severity on PHQ-9 scores with the outcome measures using univariable and multivariable linear regression models. RESULTS: Fifty-seven patients (mean age 67.8 ± 17.0 years; 50.9% male; 59.6% Caucasian) were included in the final analysis. Mean (standard deviation) outcome scores at three months were PHQ-9: 6.39 (5), Motricity Index: 86.93 (30.04), FM-UE: 52.67 (17.83), and ARAT: 43.77 (20.03). After adjusting for age, initial National Institute of Health Stroke Scale, and if patient discharged after hospitalization on a selective serotonin reuptake inhibitor, sex, and baseline motor outcome, we found that for every point increase in PHQ-9, the Motricity Index decreased by 0.82 points (p = 0.02) and the FM-UE decreased by 0.77 points (p = 0.049). CONCLUSION: Depressive symptoms are common in the stroke population. Depressive symptoms after stroke are associated with multiple types of motor impairments. We need better understanding of the biologic and psychologic aspects of depression involved in stroke recovery.

Transition Readiness Assessment in Adolescents and Young Adults with Neurofibromatosis Type 1 (NF1).

Neurofibromatosis type 1 (NF1) conveys significant disease morbidity and lower quality of life compared to the general population. Research has shown that decreased positive health outcomes are directly correlated with inadequate development of health-related self-management skills among similar patient populations, and among these populations a healthcare transition (HCT) intervention improves provision of care and health outcomes. Thus, HCT intervention may improve care and outcomes in NF1. To design a future informed NF1 HCT intervention, baseline transition readiness must be assessed. A survey distributed by Children's Tumor Foundation (CTF) was developed to assess transition readiness and the impact of NF1 on factors of young adult life. A total of 101 participants aged 14-26 years living in the United States completed the survey with a median [IQR] age of 18 [16, 21]. The majority of participants reported that NF1 had significant or some impact on all factors of young adult life including education, career, relationships, and family planning. The median Transition Readiness Assessment Questionnaire (TRAQ) score in this study (3.50/5.00) was significantly lower than the previously published score of healthy peers (3.93/5.00) (p< .001). Higher TRAQ scores correlated with higher NF1-specific transition knowledge and skills (NF1-TRAQ) (r = 0.632). Participants self-report adequate knowledge of NF1 and comfort in talking to medical providers. They report discomfort with appointment keeping, insurance related tasks, addressing NF1 emergencies, and discussing NF1 with non-medical providers and peers. Further, TRAQ and NF1-TRAQ scores were lower in individuals who reported that their diagnosis of NF1 had some or significant impact on education, career, and relationships. Findings demonstrate that among individuals with NF1 in this study, decreased transition readiness is associated with a negative impact on young adult life. Data from this study supports the need to develop NF1-specific HCT intervention tools, with an effort to improve quality of life and standardize NF1 care.

The association between pulmonary vascular disease and respiratory improvement in infants with type I severe bronchopulmonary dysplasia.

OBJECTIVE: To describe the association between echocardiographic measures of pulmonary vascular disease and time to respiratory improvement among infants with Type I severe bronchopulmonary dysplasia (sBPD). STUDY DESIGN: We measured the pulmonary artery acceleration time indexed to the right ventricular ejection time (PAAT/RVET) and right ventricular free wall longitudinal strain (RVFWLS) at 34-41 weeks' postmenstrual age. Cox-proportional hazards models were used to estimate the relationship between the PAAT/RVET, RVFWLS, and the outcome: days from 36 weeks' postmenstrual age to room-air or discharge with oxygen (≤0.5 L/min). RESULT: For 102 infants, the mean PAAT/RVET and RVFWLS were 0.27 ± 0.06 and -22.63 ± 4.23%. An abnormal measurement was associated with an increased time to achieve the outcome (PAAT/RVET: 51v24, p < 0.0001; RVFWLS; 62v38, p = 0.0006). A normal PAAT/RVET was independently associated with a shorter time to outcome (aHR = 2.04, 1.11-3.76, p = 0.02). CONCLUSION: The PAAT/RVET may aid in anticipating timing of discharge in patients with type I severe BPD.

Pediatric Heart Transplant Recipients Bridged with Biventricular Assist Device Have Worse 1 Year Graft Survival.

There are little data on postheart transplant (HT) outcomes for pediatric patients that were supported to HT with biventricular assist device (BiVAD). The United Network for Organ Sharing database was queried for patients <18 years old at time of HT between January 2005 and March 2018, excluding patients bridged with total artificial hearts and right ventricular assist device (VAD). Of 4,904 pediatric HT recipients, patients were grouped by no VAD support (3,934; 80.2%), left ventricular assist device only (736; 15%), and BiVAD (234; 4.8%). Overall graft survival analysis indicates crossing hazard rates between groups over time with the BiVAD group having a significantly lower graft survival at 1 year post-HT. A Cox model adjusted for age, era, diagnosis, and time by group interaction demonstrated increased 1 year hazard ratio (HR) of 8.5 (95% confidence intervals [CI]: 6.15-11.79) comparing BiVAD to no VAD. Comparable hazard between BiVAD and no VAD groups were found at 5 years (HR 1.01; 95% CI: 0.67-1.51), while lower hazard for the BiVAD group was found at 10 years post-HT (HR 0.07; 95% CI: 0.03-0.18). Although pre-HT BiVAD support leads to worse graft survival 1 year post-HT, long-term survival is acceptable.

Concussion Alters Dynamic Pupillary Light Responses in Children.

AIM: To investigate the impact of concussion on pupillary function in children by examining pupillometric parameters and assessing for differences in children reporting photosensitivity. METHODS: Retrospective chart review was performed of pediatric patients referred for visual symptoms after concussion from 2017 to 2018 seen in a single academic outpatient clinic. Pupillometry data of 92 patients were included. Outcomes were compared to normative pediatric data from the same institution by 2-sample t tests. The association between photosensitivity and each outcome was assessed by use of linear mixed models with photosensitivity as a fixed effect and random patient effect. RESULTS: Outcomes of 181 eyes in 92 concussion patients were averaged by patient and compared to normative values in scotopic conditions. Concussion patients had an average age of 13.8 ± 2.64 years. Average constriction velocity (P = .0008), maximum constriction velocity (P = .0012), and average dilation velocity (P = .0034) were faster in concussion patients, whereas 75% recovery times (P = .0027) was increased. Photosensitivity did not significantly affect measured pupillary responses. CONCLUSION: Dynamic pupillary responses may be increased in pediatric concussion. Pupillometry may provide insight into the complex pathophysiological changes underlying pediatric concussion.

Personalized Blood Pressure Management During Cardiac Surgery With Cerebral Autoregulation Monitoring: A Randomized Trial.

The purpose of this study was to determine if setting mean arterial pressure (MAP) targets during cardiopulmonary bypass (CPB) based on individualized cerebral autoregulation data reduces the frequency of neurological complications compared with usual care. Patients (n = 460) ≥ 55 years old at risk for neurological complications were randomized to have MAP targets during CPB to be above the lower limit of transcranial Doppler determined cerebral autoregulation versus usual institutional practices. The primary outcome was the frequency of the composite endpoint of clinical stroke, or new brain magnetic resonance imaging-detected ischemic injury, or cognitive decline 4-6 weeks after surgery from baseline. Secondary outcomes were components of the primary composite outcome and clinically detected delirium. Complete outcome data were available from 194 patients (stroke assessments, n = 460; magnetic resonance imaging data, n = 164; cognitive data n = 336). There was no difference between groups in the frequency of the composite neurological end-point or its components (P = 0.752). Compared with the usual care there was a 45% reduction in the frequency of clinically detected delirium in the autoregulation group (8.2% vs 14.9%, risk ratio = 0.55, 95% confidence interval = 0.32, 0.93, P = 0.035) and improved performance on test of memory 4-6 weeks after surgery from baseline (P = 0.019). Basing MAP during CPB on cerebral autoregulation monitoring did not reduce the frequency of the primary neurological outcome in high-risk patients compared with usual care but it was associated with a reduction in the frequency of delirium and better performance on tests of memory 4-6 weeks after surgery.

Arm Subscore of Motricity Index to Predict Recovery of Upper Limb Dexterity in Patients With Acute Ischemic Stroke.

OBJECTIVE: The aim of this study was to determine whether the arm subscore of the Motricity Index 1 wk after stroke can predict recovery of upper limb function according to the Action Research Arm Test before inpatient rehabilitation facility discharge and at 3-mo outpatient follow-up. DESIGN: This was a prospective cohort study of patients with acute ischemic stroke admitted to a single acute care hospital and affiliated inpatient rehabilitation facility between 2016 and 2018. Upper limb dexterity of the impaired limb was assessed using the arm subscore of the Motricity Index and Action Research Arm Test. Receiver operating characteristic curve analysis was used to determine optimal cutoffs of the initial arm subscore of the Motricity Index for a good functional outcome defined as Action Research Arm Test score of 45 or higher. RESULTS: Ninety-five patients were evaluated at median 6, 26, and 98.5 days after stroke. The median (interquartile range) arm subscore of the Motricity Index at 1 wk was 77 (20.3-93). The median (interquartile range) Action Research Arm Test scores before inpatient rehabilitation facility discharge and at 3-mo outpatient follow-up were 33 (3.5-52) and 52 (34-55.8), respectively. The optimal arm subscore of the Motricity Index to predict Action Research Arm Test score of 45 or higher before inpatient rehabilitation facility discharge and at 3-mo outpatient follow-up were 71 and 58, respectively. CONCLUSIONS: Early arm subscore of the Motricity Index at 1 wk predicts upper limb functional capacity before inpatient rehabilitation facility discharge and at 3-mo outpatient follow-up.

Resource utilization of intraoperative cultures for pediatric deep neck space abscesses.

INTRODUCTION: Peritonsillar (PT), parapharyngeal (PP), and retropharyngeal (RP) abscesses are common pediatric deep neck space infections (DNSI). Despite established literature on DNSI microbiology, obtaining intraoperative cultures remains commonplace. The objective was to evaluate the resource utilization of intraoperative cultures when draining PT, PP, and RP abscesses. METHODS: Pediatric patients (age <18.0 years) who underwent surgical drainage of a PT, PP, or RP abscess between January 2013 and June 2018 were retrospectively reviewed. Changes in antimicrobials based on intraoperative culture results were assessed by use of Fisher's exact tests or Wilcoxon rank-sum tests, as appropriate. Multivariable linear regression was used to model the association between factors of interest and number of cultures obtained. RESULTS: Eighty-eight patients underwent surgical drainage, of which 80 patients (median age 6.96 years) had intraoperative bacterial cultures (32 PT, 21 PP, and 27 RP). There were no positive fungal or acid-fast bacilli cultures. Seven patients had culture-directed changes in treatment; none of these patients had a PT abscess. Age was inversely associated with culture-directed changes (p = 0.006) while the use of blood cultures (p = 0.012) was positively associated with culture-directed treatment changes. Hospital length of stay (p < 0.001) and history of prior DNSI (p = 0.001) were associated with number of cultures obtained. CONCLUSIONS: Younger children with PP and RP abscesses are most likely to benefit from intraoperative bacterial cultures. Cultures of PT abscesses are unlikely to change clinical management. Fungal and acid-fast bacilli cultures are unlikely to yield clinically useful information. Prudent use of intraoperative cultures may decrease the use of hospital resources and admission-related costs.

Effects of an Implementation Intervention to Promote Use of Patient-Reported Outcome Measures on Clinicians' Perceptions of Evidence-Based Practice, Implementation Leadership, and Team Functioning.

INTRODUCTION: Patient-reported outcome measures (PROMs) are administered rarely during rehabilitation hospitalizations because clinicians are unfamiliar with their use and the technology to integrate PROMs into electronic medical records is nascent. This study evaluated an implementation intervention that targeted teams' perceptions of evidence-based practice (EBP), implementation leadership, and team functioning that might facilitate PROM use. METHODS: We compared clinicians' perceptions on three inpatient rehabilitation units, with sequential implementation across units. Clinicians completed the EBP Attitudes Scale, Implementation Leadership Scale, and the Team Functioning Survey before, shortly after, and 1 month after training. RESULTS: Forty-seven clinicians participated, including nurses (27.7%), occupational (21.3%) and physical therapists (21.3%), and two physicians. They worked on spinal cord injury (46.8%), neurologic (40.4%), or pediatric (12.8%) units. EBP Attitude Scale scores improved from preintervention to postintervention and remained above baseline levels at follow-up. The interaction between time and unit was statistically significant for the Divergence subscale such that Pediatric Unit scores increased from preintervention to postintervention and follow-up, while on the spinal cord injury, unit scores increased from preintervention to postintervention, and on the Neurologic Unit scores declined from preintervention to postintervention and follow-up. The EBP Attitudes Requirements score increased at postintervention and follow-up. The Implementation Leadership Scale Proactive score and team functioning survey scores decreased slightly. DISCUSSION: Implementing PROMs had varied effects on EBP attitudes and perceptions of leadership and team functioning. Perceptions across units were distinctive on the Evidence-Based Practice Attitudes Scale Divergence subscale. Introduction of PROMs should consider clinician attitudes regarding EBP as well as implementation leadership and team functioning.