Dynamic interaction network involving the conserved intrinsically disordered regions in human eIF5.

Translation initiation in eukaryotes requires multiple eukaryotic translation initiation factors (eIFs) and involves continuous remodeling of the ribosomal preinitiation complex (PIC). The GTPase eIF2 brings the initiator Met-tRNAi to the PIC. Upon start codon selection and GTP hydrolysis, promoted by eIF5, eIF2-GDP is released in complex with eIF5. Here, we report that two intrinsically disordered regions (IDRs) in eIF5, the DWEAR motif and the C-terminal tail (CTT) dynamically contact the folded C-terminal domain (CTD) and compete with each other. The eIF5-CTD•CTT interaction favors eIF2ß binding to eIF5-CTD, whereas the eIF5-CTD•DWEAR interaction favors eIF1A binding, which suggests how intramolecular contact rearrangement could play a role in PIC remodeling. We show that eIF5 phosphorylation by CK2, which is known to stimulate translation and cell proliferation, significantly increases the eIF5 affinity for eIF2. Our results also indicate that the eIF2ß subunit has at least two, and likely three eIF5-binding sites.

Seeing is believing: what do boys do when they find a real gun?

OBJECTIVES: To determine how boys behave when they find a handgun in a presumably safe environment and to compare parental expectations of their child's interest in real guns with this observed behavior. METHODS: A convenience sample of 8- to 12-year-old boys was recruited from families that completed a survey on firearm ownership, storage practices, and parental perceptions. Parents were asked to rate their child's interest in real guns on a scale from 1 to 5: 1-2 = low interest, 3 = moderate interest, and 4-5 = high interest. Parents of an eligible child were asked to bring to the exercise 1 of their son's playmates and/or a sibling in the same age range. After informed parental consent was obtained, each pair or trio of boys was placed in a room with a 1-way mirror and observed for up to 15 minutes. Two water pistols and an actual.380 caliber handgun were concealed in separate drawers. The handgun contained a radio transmitter that activated a light whenever the trigger was depressed with sufficient force to discharge the firearm. After the exercise, each boy was asked whether he thought that the pistol was real or a toy. Before leaving, each child was counseled about safe behavior around guns. RESULTS: Twenty-nine groups of boys (n = 64) took part in the study. The mean age of participants was 9.8 years. Twenty-one of the groups (72%) discovered the handgun (n = 48 boys); 16 groups (76%) handled it (n = 30 boys). One or more members in 10 of the groups (48%) pulled the trigger (n = 16 boys). Approximately half of the 48 boys who found the gun thought that it was a toy or were unsure whether it was real. Parental estimates of their child's interest in guns did not predict actual behavior on finding the handgun. Boys who were believed to have a low interest in real guns were as likely to handle the handgun or pull the trigger as boys who were perceived to have a moderate or high interest in guns. More than 90% of the boys who handled the gun or pulled the trigger reported that they had previously received some sort of gun safety instruction. CONCLUSION: Many 8- to 12-year-old boys will handle a handgun if they find one. Guns that are kept in homes should be stored in a manner that renders them inaccessible to children.guns, weapons, firearms, children, childhood behavior, injury prevention.

Intravenous ketorolac in the emergency department management of sickle cell pain and predictors of its effectiveness.

OBJECTIVES: To evaluate the effectiveness of intravenous (IV) ketorolac tromethamine in the treatment of children with sickle cell disease with moderate to severe acute vaso-occlusive pain (VOP) and to develop a predictive model that would determine who would need additional IV analgesics. DESIGN: A prospective case series. SETTING: The emergency department of an urban children's hospital in the southeastern United States. PATIENTS: A convenience sample of 51 children aged 6 to 18 years, representing 70 distinct episodes of VOP requiring IV analgesics. INTERVENTION: All patients were given 0.5 to 1 mg/kg IV ketorolac and IV fluids. MAIN OUTCOME MEASURES: Patients, parents, nurses, and physicians assessed pain before and after ketorolac using a standard 100-mm visual analog scale (VAS). RESULTS: Of the 70 episodes of VOP, 37 (53%) adequately resolved with IV ketorolac and IV fluids and required no IV opioids (group A). Thirty-one episodes (47%) required the addition of an IV opioid (group B). Group B had a significantly greater proportion of episodes reporting 4 or more painful sites than group A, 43% (12/28) vs 9% (3/33), respectively (P<.01). Group B also had significantly higher mean initial VAS scores than group A as assessed by the patient (81 vs 60; P<.01), parent (71 vs 54; P<.01), nurse (78 vs 51, P<.01), and physician (69 vs 53; P =.01). Of the patient assessments with an initial VAS score greater than 70, 69% (18/26) required the addition of an opioid. CONCLUSIONS: First-line therapy with IV ketorolac and IV fluids resulted in adequate resolution of pain in 53% of episodes with acute VOP. A reported 4 or more painful sites and an initial VAS score greater than 70 were predictors of the likelihood to need additional IV analgesics.

Emergency department use of ketamine in pediatric status asthmaticus.

The objective of this study was to evaluate the effects of adding ketamine to standard emergency department (ED) therapy for patients with status asthmaticus. This was a prospective observational study. Ten patients with an acute exacerbation of asthma who were unresponsive to standard therapy were enrolled in the ED. Upon enrollment, children received ketamine at a loading dose of 1 mg/kg intravenously (i.v.), followed by a continuous infusion of 0.75 mg/kg/hr (12.5 microg/kg/min) for 1 hr. Clinical asthma score (CAS), vital signs, and peak expiratory flow (PEF) measurements were obtained prior to ketamine administration, within 10 min after ketamine administration was completed, and 1 hr after infusion. Median CAS on ED arrival was 15 (range 7-23) and did not significantly change immediately prior to infusion of ketamine (median 14, range 8-21). Median CAS decreased to 10.5 immediately after infusion and to 9.51 hr post ketamine infusion (37% reduction, p < 0.05 by ANOVA vs. preketamine CAS). Median respiratory rate (RR) also decreased from 39 prior to ketamine to 30 immediately following ketamine administration (25% decrease vs. preketamine; p < 0.05). Oxygen saturation significantly improved after ketamine infusion, although 5 patients remained on oxygen. Median PEF improved after infusion, but was not statistically significant. Four patients experienced mild side effects including mild hallucinations, diffuse flushing, and moderate hypertension. Side effects resolved with benzodiazepines or with discontinuation of the infusion. Addition of ketamine to standard therapy was associated with improved indices of acute asthma severity. Side effects were transitory and comparable to previous studies. However, a double-blinded randomized controlled trial needs to be conducted to determine if improvement is attributable to the addition of ketamine to standard asthma therapy.

The utility of toxicologic analysis in children with suspected ingestions.

OBJECTIVE: To evaluate the usefulness of toxicologic studies on the management of children with suspected ingestions. DESIGN: Prospective, consecutive case series. SETTING: Two tertiary care children's hospital emergency departments. PATIENTS: All children < or =18 years of age presenting with a suspected ingestion. STUDY DESIGN: Pediatric emergency physicians completed a 14-point questionnaire on each identified patient that included demographics, signs, and symptoms, and if applicable, the extent of drug analysis performed. Pre-test and post-test utility values were determined by the ordering physician using an 11-point scale (0 = least valuable, 10 = most valuable). Physicians also assessed how positive or negative drug analyses affected patient management. RESULTS: Two hundred twenty patients met study criteria. Median age was 5 years, with males making up 53% of patients. Drug analysis was ordered in 72% (158/220) of cases, with 59% of these tests obtained for a history of ingestion and 27% obtained for altered mental status (AMS). The most common suspected ingestions were acetaminophen and cold preparations. Seventy-eight of 158 (49%) patients had positive toxicology tests, with 17 unsuspected findings. Patient management was affected in 53/158 (34%; 95% CI, 27-41%) cases. Unsuspected findings affecting management were found in only 4/158 (3%; 95% CI, 1-6%) cases. Significant differences in pre-test and post-test utility values occurred for serum assays (mean difference +0.4, P = 0.008), patients presenting with AMS (mean difference -0.8, P = 0.005), and patients having a negative drug test (mean difference -0.5, P = 0.003). Although negative drug analysis gave the physician reassurance in 39/80 (49%; 95% CI, 38-60%) cases, patient management was altered in only 8/80 (10%; 95% CI, 5-18%) cases. CONCLUSIONS: Seventy-two percent of children presenting with suspected drug ingestions had toxicologic analysis performed as part of their evaluation. Analysis was most valuable to physicians when evaluation of overdoses required serum drug levels. Qualitative urine drug screens provided minimal useful information. Unexpected findings on urine drug screening leading to changes in management were uncommon.

Firearms in the home: parental perceptions.

BACKGROUND: Each year, thousands of children are injured or killed from unintentional gunshot wounds. Discovering a gun while playing in the home places children at risk of being injured by the firearm. OBJECTIVES: To determine parental firearm storage practices and parental perceptions of the behavior of their children around guns. METHODS: Cross-sectional survey of parents of children from 4 to 12 years of age. A sample of 424 parents, bringing their children to one of five pediatric ambulatory care centers, were asked to complete a 20-point self-administered questionnaire at the time of their visit. RESULTS: A total of 400 parents (94%) completed the questionnaire; 113 parents (28%) reported keeping a firearm (most often a handgun) in the home. Firearm owners were predominantly male, 30 years of age or older, white, and married. Of the gun owners, 52% stored their firearms loaded or unlocked, and 13% kept one or more guns loaded and unlocked. Three fourths of gun-owning parents believed that their 4- to 12-year-old child could tell the difference between a toy gun and a real gun, and 23% believed that their child could be trusted with a loaded gun. Although the majority of gun-owning parents (53%) endorsed safe storage as the best firearm injury prevention strategy, 61% of parents who do not own firearms endorse not owning guns as the best way to prevent pediatric firearm injuries. CONCLUSION: A majority of gun-owning parents store their firearms loaded or unlocked, substantially underestimating the risk of injury to their children. Many firearm-owning parents trust their child with a loaded gun and believe that their young child can tell the difference between a toy gun and a real gun.

Caregiver knowledge and delivery of a commonly prescribed medication (albuterol) for children.

OBJECTIVE: To evaluate caregiver knowledge and delivery of a prescription medication (albuterol) for children. DESIGN: Prospective convenience sample. PARTICIPANTS: Caregivers listing albuterol as one of their child's medications. SETTING: Two urban, university-affiliated pediatric emergency departments. INTERVENTIONS: Caregivers were asked about their knowledge of the medication, the child's dose, frequency, duration of use, and where it was prescribed. In a mock scenario, they measured and demonstrated medication delivery to their child. Common measuring devices and formulations were offered. RESULTS: Forty-one caregivers were enrolled. Thirty-six (88%) were high school educated and 39 (95%) had a primary care provider. Twenty-six (63%) were out of medication, 7 (17%) stated an incorrect dose, 18 (44%) reported an incorrect frequency, and 10 (24%) stated an inadequate duration of use. Formulations chosen were liquid (n = 15, 37%), nebulizers (n= 15, 37%), and inhalers (n = 11, 27%). Metered dosing (metered-dosing inhaler or premixed solution) were chosen by 22 caregivers (54%), calibrated measuring tools (droppers, syringes) by 15 (37%), and noncalibrated delivery devices (teaspoon) by 4 (10%). An improper dose was measured by 9 (22%), and the dose intended was inaccurately measured by 7 (17%). All caregivers using a teaspoon inaccurately measured their intended dose of the liquid formulation. CONCLUSIONS: Metered dosing and calibrated measuring devices aided in the accurate delivery of this prescription medication. However, considerable concern exists with the use of noncalibrated measuring devices (teaspoons), improper frequency, and duration of use. Refilling of medication was also a concern since 63% were out of albuterol. Caregiver education on use, delivery, and refilling of medications must be stressed and assessed at all emergency department and primary care visits. In addition, metered dosing and the use of calibrated measuring devices should be encouraged.

Utility of comprehensive toxicologic screens in children.

This study was undertaken to evaluate the clinical utility and cost-effectiveness of the limited component versus the high performance liquid chromatography (HPLC) component of comprehensive toxicologic screens in children. A retrospective patient series was studied at the emergency department (ED) of Hughes Spalding Children's Hospital, an urban, tertiary-care ED, consisting of all patients younger than 19 years of age who had a comprehensive toxicologic screen between January 1994 and July 1995. The comprehensive test included a broad-spectrum HPLC component as well as a limited component that examined serum for ethanol, aspirin, and acetaminophen and urine for benzodiazepines, barbiturates, amphetamines, cocaine, phencyclidine, and opiates. All toxicologic screens were reviewed for the presence of exogenous toxins, followed by a chart review of all patients with positive screens and a selection of negative screens. Toxins were categorized as (1) iatrogenic or noniatrogenic, (2) clinically or nonclinically suspected by history and physical, and (3) clinically or nonclinically significant. Comprehensive toxicology screens were performed in 463 cases during the study period; 234 (51%) were positive for exogenous toxins. In 227 of 234 positive screens (97%), toxins were either suspected by history and/or physical, were present on the limited portion of the toxicology screen, or were clinically insignificant. The remaining 7 of the 234 positive screens (3%) were clinically significant and detected solely by the broad-spectrum HPLC portion of the comprehensive screen. However, in none of these 7 cases was patient management clinically altered as a result of the positive screen. The total additional cost for the HPLC component was $16,205 ($35x463), an average distributive charge of $2,315 per patient in whom the HPLC portion provided additional clinical information ($16,205/7). Although adding significant charges to the evaluation of suspected toxic exposures in children, the HPLC component of the comprehensive drug screen was of no additional clinical benefit compared with its limited component alone.

Pseudoparalysis of the lower extremity in an infant.

We describe a case of septic arthritis of the knee in an afebrile, well-appearing four-month-old female. She had been evaluated previously for lower extremity disuse attributed to antecedent trauma. Her physical examination was remarkable only for limitation of extension of the affected leg at the knee. Emergency physicians should understand the physical examination findings suggesting joint effusion and the need to consider osteomyelitis/septic arthritis in children less than one year of age with pseudoparalysis.

Lacerations against Langer's lines: to glue or suture?

This study evaluated the effects of initial wound orientation on the cosmetic outcome of facial lacerations repaired with histoacryl blue (HAB), a tissue adhesive, vs. conventional suturing. This was a retrospective analysis of patients from a prospective randomized clinical trial on the use of HAB. Children in the initial cohort who had facial lacerations and were also evaluated for cosmetic appearance at a 2-month follow-up appointment were eligible. Orientation along Langer's Lines, which define the functional anatomy of the underlying structures to the skin, was determined by two investigators blinded to the initial method of repair. Photographs of the wounds were reviewed and the wounds were categorized as being: Langer (+) (<20 degrees deviated from Langer's Lines) or Langer (-) (> or =20 degrees deviated from Langer's Lines). Photographic appearance at follow-up was evaluated using a 100-mm visual analog scale (0=best, 100=worst) by two plastic surgeons blinded to the method of repair. Sixty-one patients were enrolled in the initial cohort, with 55 (90%) evaluated at the 2-month follow-up. Forty-eight of the 55 (87%) had facial lacerations, therefore meeting present study criteria: [HAB (n=26), Suturing (n=22), Langer (+) (n=27), Langer (-) (n=21)]. Langer (+) patients were comparable to Langer (-) for demographics, wound characteristics, and method of repair. There was no difference in overall cosmetic appearance of facial wounds closed with HAB vs. conventional suturing. Follow-up appearance was significantly worse for sutured Langer (-) vs. Langer (+) wounds. In contrast, cosmetic appearance of lacerations closed by HAB were comparable between Langer (-) and Langer (+) wounds. In conclusion, initial wound orientation had a greater impact on the cosmetic appearance for lacerations closed by suturing compared to HAB. HAB may be the preferred method of cutaneous closure for facial lacerations oriented against Langer's Lines.

A prospective evaluation of pediatric emergency care during the 1996 Summer Olympic Games in Atlanta, Georgia.

OBJECTIVES: To explore the impact that a temporary influx of millions of people can make on the local pediatric emergent and urgent care systems. The spectrum of illness was also explored. DESIGN/METHODS: Prospective cohort of patients from outside the usual catchment area presenting at two children's emergency departments and their satellite urgent care centers during the 1996 Summer Olympics. A 13-point survey was completed on each which included general demographics, transportation, language, time in the area, chief complaint, past medical conditions, diagnosis, and medical complications or problems related to their visit. RESULTS: A total of 263 patients met criteria, mean age 6.7 years. Twenty-four percent were seen in the tertiary care centers and 76% in urgent care. Twenty-three countries with 15 primary languages were represented. Fifty-one percent were in Atlanta for less than seven days, and 44% were uninsured. Most presented with common concerns including; fevers, rashes, respiratory difficulty, and minor trauma. Children were sicker than our typical emergency department patients, with hospital admission rates two times the usual for the tertiary care children's hospital (27% vs 13%) and the county children's hospital (7% vs 3%). Nineteen (7.2%) had unusual presentations or difficulty with care. Notably, five had language barriers; three had serious chronic conditions of unknown detail to the temporary caregiver; two did not bring vital medical supplies (ie, spare tracheotomy tube); one mislabeled medications, causing an overdose; one had leukemia, needed transfusion, but did not know of the regional centers; and one required helicopter transport secondary to traffic. CONCLUSION: A large influx of people resulted in a relatively minor impact on the emergent care system for children. Care could have been improved if those with chronic illnesses were better informed of regional health care centers, essential medical needs for travel, and if travel included a physician's medical summary. In addition, anticipation of the Olympic Games helped the pediatric emergency medicine community improve disaster preparedness, and enhance its working relationship with the adult emergency medicine community and the regional poison center. Ongoing efforts for disaster preparedness with periodic reevaluation have also been established.

Societal savings by "fast tracking" lower acuity patients in an urban pediatric emergency department.

To evaluate the cost-effectiveness of a "fast track" system for diverting lower acuity patients away from the pediatric emergency department (ED), 4,060 patients triaged to the fast track area of an urban pediatric ED with the 10 most common discharge diagnoses from 1/1/94 through 12/31/94 were retrospectively evaluated. Patients triaged as having nonurgent concerns qualified for treatment in a separate fast track area for 8 hours per day (fast track patients). These patients were compared with 5,199 seen in the main pediatric ED for the same concerns during the remaining hours when the fast track was not in operation (ED patients). Computer records were reviewed for demographics, acuity levels, diagnosis, and collection ratios (revenues/charges). The societal savings was calculated as sigma $ [(delta mean revenue of diagnosis1-10 in the main ED - mean revenue of diagnosis1-10 in the fast track) x the number of patients seen in fast track for diagnosis1-10] stratified by acuity. Collection ratios were comparable between groups (57% v 62%), but the average charges (physician and facility) were significantly less for patients seen in the fast track by a ratio of 1:2.4 (P < .0001). The average net revenue was also significantly less for all patients seen in the fast track by a ratio of 1:2.6 (P < .0001). When stratified by diagnosis and acuity, the savings to society was $101,313, or an average of $25/patient seen in the fast track ($101,313 per 4,060). A fast track is an effective system for maintaining patient flow at a cost savings to society. It can help the hospital in its negotiations with payors because it curtails charges. It is also a potential means for maintaining overall departmental revenues as payors increasingly deny traditional pediatric ED visits for patients with lower acuity concerns.

Over-the-counter medications. Do parents give what they intend to give?

OBJECTIVE: To evaluate caregiver (parent or guardian) use of over-the-counter medications (OTCs) as related to the accuracy and correctness of dosing for children seen at a pediatric emergency department with nonemergent concerns. DESIGN: Prospective patient series. SETTING: A tertiary care pediatric emergency center. PARTICIPANTS: A representative sample of children with nonemergent chief complaints. INTERVENTIONS: A questionnaire about general demographic characteristics, recent OTC use, and medical history of the patients was given to each caregiver. A mock scenario was then presented that required the caregivers to determine and measure a correct dose of acetaminophen for their child. A dose of 9 to 16.5 mg/kg was considered correct. Accuracy of measuring was considered within +/-20% of the caregivers' stated intended dose for their child. RESULTS: One hundred caregivers were enrolled in the study. Mean caregivers' age was 29 years, with 82% having at least a high school education. Seventy-seven percent of their children used OTCs within the previous 2 months, and Tylenol (acetaminophen) was the most commonly used. While 66% of the caregivers reported Tylenol use, only 8% reported the use of acetaminophen. During the dosing scenario, only 40% of the caregivers stated an appropriate dose for their child and only 67% accurately measured the amount of acetaminophen they intended. Forty-three percent measured out a correct amount of acetaminophen for their child. However, almost one third of these occurred strictly by accident because they inaccurately measured an improper intended dose. Combining these results, only 30% of the caregivers were able to demonstrate both an accurately measured and correct dose for their child. CONCLUSIONS: Although a large number of caregivers administer OTCs, knowledge of these medications, and accuracy and correctness of dosing remain a marked concern. Improved caregiver education on the accuracy and correctness of dosing OTCs is necessary.

Long-term appearance of lacerations repaired using a tissue adhesive.

BACKGROUND: Histoacryl Blue (HAB), a tissue adhesive, has been shown to decrease laceration repair time, cause less pain to the child, eliminate the need for suture removal, and result in a similar short-term cosmetic outcome compared with conventional suturing. Reports suggest that poor correlation can exist between the short-term and long-term cosmetic outcomes for lacerations repaired by conventional suturing. Therefore, this study compares the long-term cosmetic outcome of HAB to conventional suturing for laceration repair in children. DESIGN: Prospective, randomized clinical trial. PARTICIPANTS: Children presenting an urban pediatric emergency department for laceration repair between October 1994 and February 1995 were eligible. Patients less than 1 or more than 18 years old, those with lacerations more than 5 cm in length, or in areas of high tension or mobility were excluded. INTERVENTIONS: After routine wound management, including subcutaneous closure when deemed necessary, patients were randomized to receive skin sutures or HAB for cutaneous closure. Photographs taken at the 2-month and 1-year follow-up visits were evaluated for cosmetic appearance by two plastic surgeons blinded to the method of repair. RESULTS: Sixty-one children were enrolled: HAB (N = 30), suture (N = 31). Thirty HAB and 25 sutured patients were assessed at 2 months, while 17 HAB and 15 sutured patients were reevaluated at 1 year. Patients that followed-up at 2 months and 1 year were comparable to those with no follow-up in: treatment group (HAB vs suture), demographics, wound characteristics, and initial parental satisfaction. The two plastic surgeons graded the cosmetic appearance of the wounds repaired by HAB to be comparable to those repaired by conventional suturing at both the 2-month and 1-year follow-up. CONCLUSIONS: The use of HAB is an ideal alternative to conventional suturing for the cutaneous closure of low tension lacerations in children with a long-term cosmetic outcome comparable to conventional suturing.