Implementation of active injury management (AIM) in youth with acute concussion: A randomized controlled trial.

BACKGROUND: Nearly 2 million youth seek acute medical care following concussion in the U.S. each year. Current standard of care recommends rest for the first 48 h after a concussion. However, research suggests that prolonged rest may lengthen recovery time especially for patients with certain risk profiles. Research indicates that physical activity and behavioral management interventions (sleep, stress management) may enhance recovery. To date, there is limited empirical evidence to inform acute (<72 h) concussion recommendations for physical activity and behavioral management in adolescents. OBJECTIVE: To determine the effectiveness of physical activity and behavioral management for acute concussion in adolescents and young adults, and to evaluate the role of patient characteristics on treatment response. METHODS: This multicenter prospective randomized controlled trial will determine which combination of physical activity and behavioral management is most effective for patients 11-24 years old who present to the emergency department or concussion clinic within 72 h of injury. Participants are randomized into: 1) rest, 2) physical activity, 3) mobile health application (mHealth) behavioral management, or 4) physical activity and mHealth app conditions. Assessments at enrollment, 3-5 days, 14 days, 1 month, and 2 months include: concussion symptoms, balance, vestibular-ocular and cognitive assessments, quality of life, and recovery time. Somatic symptoms and other risk factors are evaluated at enrollment. Compliance with treatment and symptoms are assessed daily using actigraph and daily self-report. The primary study outcome is symptoms at 14 days. CONCLUSION: Prescribed physical activity and behavioral management may improve outcomes in youth following acute concussion.

The point mutation UCH-L1 C152A protects primary neurons against cyclopentenone prostaglandin-induced cytotoxicity: implications for post-ischemic neuronal injury.

Cyclopentenone prostaglandins (CyPGs), such as 15-deoxy-Δ(12,14)-prostaglandin J2 (15dPGJ2), are reactive prostaglandin metabolites exerting a variety of biological effects. CyPGs are produced in ischemic brain and disrupt the ubiquitin-proteasome system (UPS). Ubiquitin-C-terminal hydrolase L1 (UCH-L1) is a brain-specific deubiquitinating enzyme that has been linked to neurodegenerative diseases. Using tandem mass spectrometry (MS) analyses, we found that the C152 site of UCH-L1 is adducted by CyPGs. Mutation of C152 to alanine (C152A) inhibited CyPG modification and conserved recombinant UCH-L1 protein hydrolase activity after 15dPGJ2 treatment. A knock-in (KI) mouse expressing the UCH-L1 C152A mutation was constructed with the bacterial artificial chromosome (BAC) technique. Brain expression and distribution of UCH-L1 in the KI mouse was similar to that of wild type (WT) as determined by western blotting. Primary cortical neurons derived from KI mice were resistant to 15dPGJ2 cytotoxicity compared with neurons from WT mice as detected by the WST-1 cell viability assay and caspase-3 and poly ADP ribose polymerase (PARP) cleavage. This protective effect was accompanied with significantly less ubiquitinated protein accumulation and aggregation as well as less UCH-L1 aggregation in C152A KI primary neurons after 15dPGJ2 treatment. Additionally, 15dPGJ2-induced axonal injury was also significantly attenuated in KI neurons as compared with WT. Taken together, these studies indicate that UCH-L1 function is important in hypoxic neuronal death, and the C152 site of UCH-L1 has a significant role in neuronal survival after hypoxic/ischemic injury.

Hypothermia and hyperthermia in children after resuscitation from cardiac arrest.

OBJECTIVE: In experimental models of ischemic-anoxic brain injury, changes in body temperature after the insult have a profound influence on neurologic outcome. Specifically, hypothermia ameliorates whereas hyperthermia exacerbates neurologic injury. Accordingly, we sought to determine the temperature changes occurring in children after resuscitation from cardiac arrest. STUDY DESIGN: The clinical records of 13 children resuscitated from cardiac arrest were analyzed. Patients were identified through the emergency department and pediatric intensive care unit arrest logs. Only patients surviving for > or =12 hours after resuscitation were considered for analysis. Charts were reviewed for body temperatures, warming or cooling interventions, antipyretic and antimicrobial administration, and evidence of infection. RESULTS: Seven patients had a minimum temperature (T min) of < or =35 degrees C and 11 had a maximum temperature (T max) of > or =38.1 degrees C. Hypothermia often preceded hyperthermia. All 7 patients with T min < or =35 degrees C were actively warmed with heating lamps and 5 of 7 responded to warming with a rebound of body temperatures > or =38.1 degrees C. None of the 6 patients with T min >35 degrees C were actively warmed but all developed T max > or =38.1 degrees C. Six patients received antipyretics and 11 received antibiotics. Fever was not associated with a positive culture in any case. Conclusion. Spontaneous hypothermia followed by hyperthermia is common after resuscitation from cardiac arrest. Temperature should be closely monitored after cardiac arrest and fever should be managed expectantly.

Oral versus initial intravenous therapy for urinary tract infections in young febrile children.

BACKGROUND: The standard recommendation for treatment of young, febrile children with urinary tract infection has been hospitalization for intravenous antimicrobials. The availability of potent, oral, third-generation cephalosporins as well as interest in cost containment and avoidance of nosocomial risks prompted evaluation of the safety and efficacy of outpatient therapy. METHODS: In a multicenter, randomized clinical trial, we evaluated the efficacy of oral versus initial intravenous therapy in 306 children 1 to 24 months old with fever and urinary tract infection, in terms of short-term clinical outcomes (sterilization of the urine and defervescence) and long-term morbidity (incidence of reinfection and incidence and extent of renal scarring documented at 6 months by 99mTc-dimercaptosuccinic acid renal scans). Children received either oral cefixime for 14 days (double dose on day 1) or initial intravenous cefotaxime for 3 days followed by oral cefixime for 11 days. RESULTS: Treatment groups were comparable regarding demographic, clinical, and laboratory characteristics. Bacteremia was present in 3.4% of children treated orally and 5.3% of children treated intravenously. Of the short-term outcomes, 1) repeat urine cultures were sterile within 24 hours in all children, and 2) mean time to defervescence was 25 and 24 hours for children treated orally and intravenously, respectively. Of the long-term outcomes, 1) symptomatic reinfections occurred in 4.6% of children treated orally and 7.2% of children treated intravenously, 2) renal scarring at 6 months was noted in 9.8% children treated orally versus 7.2% of children treated intravenously, and 3) mean extent of scarring was approximately 8% in both treatment groups. Mean costs were at least twofold higher for children treated intravenously ($3577 vs $1473) compared with those treated orally. CONCLUSIONS: Oral cefixime can be recommended as a safe and effective treatment for children with fever and urinary tract infection. Use of cefixime will result in substantial reductions of health care expenditures.

10 kD mitochondrial matrix heat shock protein mRNA is induced following global brain ischemia in the rat.

Heat shock proteins (HSP's) are a family of highly conserved proteins whose expression is increased by stress. The expression of many HSP's is induced in neurons by ischemia; however, the response of the 10 kDa mitochondrial matrix HSP (HSP10) is less well characterized. To address this issue, asphyxial cardiac arrest was induced in 28 male Sprague-Dawley rats. Northern blot analysis revealed that hsp10 mRNA was increased 2.7-fold in asphyxiated rats compared to sham-operated controls. In situ hybridization demonstrated increased mRNA in the cortex, septal nuclei, hippocampus, thalamic nuclei, purkinje cell layer of the cerebellum, and isolated brainstem nuclei of asphyxiated rats. The increase of mRNA was most robust 8 h after the injury but remained increased for 72 h. These results show that hsp10 mRNA is increased following asphyxial cardiac arrest in rats and suggest that hsp10 could be another determinate of neuronal survival after ischemia.

Albuterol delivered via metered-dose inhaler with spacer for outpatient treatment of young children with wheezing.

OBJECTIVE: To determine the efficacy of albuterol delivered via metered-dose inhaler with spacer for the treatment of wheezing infants. DESIGN AND SETTING: Double-blind, prospective, placebo-controlled, clinical crossover trial undertaken at the emergency department of a university-affiliated children's hospital. PARTICIPANTS: Forty-two patients aged 1 to 18 months presenting to the emergency department with wheezing. INTERVENTION: Subjects were randomly assigned to one of two blinded treatment groups. Group 1 received two albuterol treatments followed by two placebo treatments. Group 2 received two placebo treatments followed by two albuterol treatments. Each treatment consisted of two puffs from a metered-dose inhaler with spacer at 20-minute intervals. MEASUREMENTS/MAIN RESULTS: On enrollment and 20 minutes after each treatment, a clinical assessment was made by the principal investigator, which included heart rate, respiratory rate, pulse oximetry, wheezing score (0 to 3), and retraction score (0 to 3). Both treatment groups had statistically significant improvement in mean wheezing score associated with albuterol therapy (P < .05 using Dunnett's t test). Mean retraction score improved over time in both groups only during drug therapy. However, the improvement of only group 2 reached statistical significance (P < .05 using Dunnett's t test). Scores were then classified as "improved" and "not improved" for analysis with McNemar's test. Group 2 had a statistically significant proportion of patients with improved retraction score related to albuterol therapy. The remaining dichotomized results, while not achieving statistical significance, showed a trend in the direction expected from a beneficial drug effect. CONCLUSIONS: Albuterol delivered by metered-dose inhaler with spacer to wheezing infants aged 1 to 18 months reduces the severity of wheezing and retractions.

ATP-MgCl2 pre-treatment in an animal model of asphyxial arrest.

ATP-MgCl2 treatment has been found to be a promising intervention in many models of hypoxic/ischemic injury. In this study, the effect of pre-treatment with ATP-MgCl2 on the hemodynamic response to asphyxia in the rat was examined. Rats were anesthetized with halothane and N2O2. A tracheostomy and femoral artery and vein cutdowns were performed. Rats were infused intravenously with either ATP-MgCl2 (approximately 50 mumol/kg) or normal saline (control group) over 15 min. Animals were then asphyxiated for 8 min by occlusion of the ventilator tubing. Following the asphyxia, 1 min of cardiopulmonary resuscitation (CPR) was attempted. Heart rate and blood pressure were monitored continuously throughout the experiment. A total of 41 animals (21 ATP-MgCl2, 20 control) were studied. Analysis of variance (ANOVA) was used to test for differences between groups. The ATP-MgCl2 group had a lower heart rate (HR) and mean arterial pressure (MAP) during the infusion. During asphyxia the ATP-MgCl2 group had a lower MAP but higher HR when compared to the control group. No significant differences were observed in the rates of successful resuscitation between ATP-MgCl2-treated rats (10 of 21, 48%) and controls (12 of 20, 60%). Possible reasons for the apparent lack of benefit of ATP-MgCl2 therapy are discussed.

Utility of blood cultures in pediatric patients found to have pneumonia in the emergency department.

STUDY OBJECTIVE: To determine the prevalence of bacteremia in pediatric patients with radiographic evidence of pneumonia in whom blood cultures were obtained. METHODS: We carried out a retrospective review of the radiology log of a tertiary care children's hospital to identify patients with radiographic evidence of pneumonia seen between August 1991 and July 1992. These patients were cross-referenced with the hospital laboratory information system, yielding results of any CBC or blood cultures. RESULTS: We found 939 patients with chest radiography findings consistent with pneumonia. Blood culturing was performed in 409 (44%). Eleven of these cultures (2.7%) grew pathogenic bacteria. Review of the medical records revealed no changes in clinical management made on the basis of the results of the blood cultures. CONCLUSION: Blood cultures are uncommonly positive in outpatients diagnosed with pneumonia.

Two children with lethargy and intussusception.

The cases of two patients with lethargy as the predominant symptom of intussusception are described. The first patient was admitted to the pediatric ICU with unexplained lethargy. The diagnosis of intussusception was made after he developed right lower quadrant abdominal tenderness and heme-positive stool. The second patient was diagnosed after presenting to the emergency department with intermittent lethargy, right lower quadrant abdominal tenderness, and heme-positive stool. The presence of gastrointestinal symptoms or signs in association with lethargy should alert the physician to the possibility of an intussusception.

Pediatric patients requiring CPR in the prehospital setting.

STUDY OBJECTIVE: To determine the outcome of pediatric patients with prehospital cardiopulmonary arrest. DESIGN: Chart review of all patients with prehospital cardiopulmonary arrest who were subsequently admitted to a pediatric emergency department from January 1988 to January 1993. Cardiopulmonary arrest was considered to have been present if assisted ventilation and chest compressions were performed on an apneic, pulseless patient. SETTING: Pediatric ED. PARTICIPANTS: Pediatric patients in prehospital cardiac arrest. RESULTS: In all, 95 patients were identified. Fifty-six had initial hospital care at the pediatric ED (primary patients). The remaining 39 were transported to the pediatric ED after initial care of another institution (secondary patients). Forty-one percent of patients were younger than 1 year. Most arrests were respiratory in origin; asystole was the most common dysrhythmia. Fifteen patients (27%) survived to discharge. Fourteen of the survivors had return of spontaneous circulation before ED arrival. Thirty-three patients were in arrest on ED arrival; in 16 (48%) of these, return of spontaneous circulation subsequently developed in the ED, and 1 survived to discharge. Two survivors, including the survivor with return of spontaneous circulation in the ED, had severe neurologic sequelae. Ten (26%) of the secondary patients survived. All survivors had return of spontaneous circulation before arrival in the ED. Two survivors had severe neurologic sequelae. CONCLUSION: Most successfully resuscitated pediatric arrest victims are resuscitated in the prehospital setting and do not suffer severe neurologic injury. Most patients who present to the ED in continued arrest and survive to discharge have severe neurologic injury.

Circumferential pressure as a rapid method to assess intraosseous needle placement.

This study was done to determine whether the application of circumferential pressure about an intraosseous (IO) site can be used as a rapid method to detect incorrect placement of an IO needle. We used a prospective, randomized, controlled canine tibial IO model. According to random assignment, IO needles were placed either intramedullary (correct placement) or extramedullary (incorrect placement) in the anteromedial tibias of 12 euthanized mongrel dogs. Neonatal blood pressure cuffs were placed contiguously above and below the IO needles. One-liter bags of solution were connected to the IO needles via blood tubing. The gravity-dependent rate of flow at each site was measured with and without the blood pressure cuffs inflated to 120 mmHg. Eleven IO needles were correctly placed and 13 were incorrectly placed. Following inflation of the blood pressure cuffs, the mean percent decrease in flow was 48% for the correctly placed IO needles, and 95% for the incorrectly placed IO needles. A two-way repeated measure of analysis of variance was significant between groups (P = 0.006), and a significant interaction was found between groups and flow rates over time (P = 0.043). We conclude that circumferential pressure about an IO infusion site can be used as a rapid method to detect incorrect placement of the IO needle.

Anomalous left coronary artery masquerading as infantile bronchiolitis.

Four infants less than six months of age with anomalous left coronary artery from the pulmonary artery who present with symptoms of wheezing are described. All had cardiomegaly on chest radiographs and because of wheezing received beta-agonist agents (albuterol alone or with epinephrine). One developed cardiopulmonary collapse secondary to supraventricular tachycardia after administration of these agents. The literature is reviewed for utility of chest radiographs in infants presenting with wheezing and for the efficacy of beta-adrenergic agents in infants less than six months of age. The authors suggest that physicians have a low threshold for obtaining a chest radiograph prior to treating a first-time wheezing infant less than six months of age with a beta-agonist agent.

Miniature C-arm imaging: an in vitro study of detecting foreign bodies in the emergency department.

STUDY OBJECTIVE: Recently, we have had clinical success detecting foreign bodies (FBs) using a mobile C-arm fluoroscopic device. This study tests its utility to detect FBs of differing densities in soft tissue. DESIGN: Blinded, randomized, controlled in vitro study. METHODS: Two physicians used the Xi-scan mini C-arm to image FBs. Five FBs of differing densities were studied: metal, gravel, glass, wood, and plastic. The FBs were placed into the deep muscles of chicken legs. One hundred observations were made: 50 legs with FBs and 50 legs without FBs. The blinded investigators imaged the legs and determined the presence or absence of FBs. RESULTS: Imaging located 100% of metal, gravel and glass FBs. Plastic and wood could not be consistently detected (sensitivity 0.4, specificity 0.6). CONCLUSIONS: This device accurately detects metal, gravel and glass. Radiolucent (wood) and semiradiopaque (plastic) FBs could not be located reliably. Clinical trials would define utility of this device in saving time, money and radiation exposure.

Use of the Morris water maze and acoustic startle chamber to evaluate neurologic injury after asphyxial arrest in rats.

The study was performed to assess the utility of the Morris water maze (MWM) and acoustic startle reflex (ASR) for evaluating neurologic outcome in a rat model of asphyxial cardiac arrest. Rats were anesthetized, intubated, and chemically paralyzed. Control animals were decannulated and, after awakening, were extubated and returned to their housing. Experimental animals were asphyxiated by disconnecting the ventilator. Approximately 3.5 min after the disconnection, there was no measurable pulse. After 7 min of asphyxia, they were then resuscitated with resumed ventilation, chest compressions, epinephrine, and sodium bicarbonate. All animals were assigned to either MWM or ASR testing. The MWM is a 6-ft diameter tank filled with opaque water. In a fixed location of the tank, a 4-inch diameter escape platform is submerged just below the surface. MWM animals were tested on post-injury d 16-21 by recording the path and time taken to escape from three randomly assigned locations per d. ASR animals had s.c. leads placed over the right triceps and tibialis anterior muscles. The latency and rectified amplitude of the ASR was measured by recording the electromyographic impulse generated when the animal was startled by an acoustic stimulus. Animals were tested on post-injury d 6 and 7. After the last test session for each group, the animals' brains were removed for histopathologic examination. Asphyxiated MWM animals took longer to find the platform, and their paths were less direct than control animals (analysis of variance p < 0.05). The ASR of asphyxiated ASR animals had greater amplitude and shorter latency compared with controls (analysis of variance p < 0.05). Histologic examination revealed no abnormalities in control animals, but 80% of asphyxiated brains showed hippocampal neuronal injury and/or reactive gliosis in the CA1 segment. Abnormalities were more commonly detected in animals killed 7 d post-injury (ASR protocol) compared with animals killed 21 d post-injury (MWM protocol). We conclude that the MWM and ASR are useful for detecting neuronal injury in asphyxiated rats.

Delayed, spontaneous hypothermia reduces neuronal damage after asphyxial cardiac arrest in rats.

OBJECTIVE: Core temperature is reduced spontaneously after asphyxial cardiac arrest in rats. To determine whether spontaneous hypothermia influences neurologic damage after asphyxial arrest, we compared neurologic outcome in rats permitted to develop spontaneous hypothermia vs. rats managed with controlled normothermia. INTERVENTIONS: Male Sprague-Dawley rats were asphyxiated for 8 mins and resuscitated. After extubation, a cohort of rats was managed with controlled normothermia (CN) by placement in a servo-controlled incubator set to maintain rectal temperature at 37.4 degrees C for 48 hrs. CN rats were compared with permissive hypothermia (PH) rats that were returned to an ambient temperature environment after extubation. Rats were killed at either 72 hrs (PH72hr, n = 14; CN72hr, n = 9) or 6 wks (PH6wk, n = 6, CN6wk, n = 6) after resuscitation. PH72 rats were historic controls for the CN72 rats, whereas PH6 and CN6 rats were randomized and studied contemporaneously. MEASUREMENTS: A clinical neurodeficit score (NDS) was determined daily. A pathologist blinded to group scored 40 hematoxylin and eosin -stained brain regions for damage by using a 5-point scale (0 = none, 5 = severe). Quantitative analysis of CA1 hippocampus injury was performed by counting normal-appearing neurons in a defined subsection of CA1. MAIN RESULTS: Mean rectal temperatures measured in the PH6wk rats (n = 6) were 36.9, 34.8, 35.5, 36.7, and 37.4 degrees C at 2, 8, 12, 24, and 36 hrs, respectively. Mortality rate (before termination) was lower in PH compared with CN (0/20 vs. 7/15; p < .005). PH demonstrated a more favorable progression of NDS (p = .04) and less weight loss (p < .005) compared with CN. Median histopathology scores were lower (less damage) in PH72hr vs. CN72hr for temporal cortex (0 vs. 2.5), parietal cortex (0 vs. 2), thalamus (0 vs. 3), CA1 hippocampus (1.5 vs. 4.5), CA2 hippocampus (0 vs. 3.5), subiculum (0 vs. 4), and cerebellar Purkinje cell layer (2 vs. 4) (all p < .05). There was almost complete loss of normal-appearing CA1 neurons in CN72hr rats (6 +/- 2 [mean +/- SD] normal neurons compared with 109 +/- 12 in naïve controls). In contrast, PH72hr rats demonstrated marked protection (97 +/- 23 normal-appearing neurons) that was still evident, although attenuated, at 6 wks (42 +/- 24 normal-appearing neurons, PH6wk). CONCLUSION: Rats resuscitated from asphyxial cardiac arrest develop delayed, mild to moderate, prolonged hypothermia that is neuroprotective.

Action sequence for layperson cardiopulmonary resuscitation.

Although some minor modifications were forged, the general consensus was to maintain most of the current guidelines for phone first/phone fast, no-assisted-ventilation CPR, the A-B-C (vs C-A-B) sequence of CPR, and the recovery position. The decisions to leave these guidelines as they are were based on a lack of evidence to justify the proposed changes, coupled with a reluctance to make revisions that would require major changes in worldwide educational practices without such evidence.Nonetheless, some major changes were made. The time-honored procedure ol pulse check by lay rescuers was eliminated altogether and replaced with an assessment for other signs of circulation. Likewise, it was recommended that even the professional rescuer now check for these other signs of circulation. Although professional rescuers may simultaneously check for a pulse, they should do so only for a short period of time (within 10 seconds). There was also enthusiasm for deleting the ventilation aspect of EMS dispatcher-assisted CPR instructions that are provided to rescuers at the scene who are inexperienced in CPR. lt was made clear, though, that the data are applicable only to adult patients who are receiving CPR and that the data are appropriate most for EMS systems with rapid response times.