Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome.

Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder mainly affecting females and is associated with mutations in MECP2, the gene encoding methyl CpG-binding protein 2. Mouse models suggest that recombinant human insulin-like growth factor 1 (IGF-1) (rhIGF1) (mecasermin) may improve many clinical features. We evaluated the safety, tolerability, and pharmacokinetic profiles of IGF-1 in 12 girls with MECP2 mutations (9 with RTT). In addition, we performed a preliminary assessment of efficacy using automated cardiorespiratory measures, EEG, a set of RTT-oriented clinical assessments, and two standardized behavioral questionnaires. This phase 1 trial included a 4-wk multiple ascending dose (MAD) (40-120 µg/kg twice daily) period and a 20-wk open-label extension (OLE) at the maximum dose. Twelve subjects completed the MAD and 10 the entire study, without evidence of hypoglycemia or serious adverse events. Mecasermin reached the CNS compartment as evidenced by the increase in cerebrospinal fluid IGF-1 levels at the end of the MAD. The drug followed nonlinear kinetics, with greater distribution in the peripheral compartment. Cardiorespiratory measures showed that apnea improved during the OLE. Some neurobehavioral parameters, specifically measures of anxiety and mood also improved during the OLE. These improvements in mood and anxiety scores were supported by reversal of right frontal alpha band asymmetry on EEG, an index of anxiety and depression. Our data indicate that IGF-1 is safe and well tolerated in girls with RTT and, as demonstrated in preclinical studies, ameliorates certain breathing and behavioral abnormalities.

Recurrence and outcomes of Stevens-Johnson syndrome and toxic epidermal necrolysis in children.

OBJECTIVES: To report clinical course, etiology, management, and long-term outcomes of children suffering from Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). METHODS: We conducted a study of all pediatric patients with SJS or TEN admitted between 2000 and 2007 to the Hospital for Sick Children and Children's Hospital Boston, and particular attention was paid to clinical manifestations, etiology, mortality, and long-term outcomes. RESULTS: We identified 55 cases of SJS (n = 47), TEN (n = 5), or SJS/TEN overlap syndrome (n = 3). Drugs were identified as the most likely etiologic agent in 29 children (53%); antiepileptic drugs were the most common agents (n = 16), followed by sulfonamide antibiotics (n = 7) and chemotherapy drugs (n = 2). Acute Mycoplasma pneumoniae infection was confirmed in 12 children (22%), and herpes simplex virus was confirmed in 5 children (9%). Treatment regimens differed significantly between participating sites and included systemic antimicrobial agents (67%), systemic corticosteroids (40%), and antiviral drugs (31%). Intravenous immunoglobulin was administered to 21 children (38%), of whom 8 received concomitant systemic corticosteroids. Ten children (18%) had recurrence of SJS up to 7 years after the index episode, and 3 experienced multiple recurrences. Twenty-six children (47%) suffered long-term sequelae that mostly involved the skin and eyes. CONCLUSIONS: Mortality rate in children was lower than that reported in adults, but half of affected children suffered long-term complications. The recurrence rate of SJS was high (1 in 5), which suggests vulnerability and potential genetic predisposition. In the absence of standardized management guidelines for these conditions, treatment regimens differed significantly between participating institutions.

Adverse drug events in the outpatient setting: an 11-year national analysis.

PURPOSE: Adverse drug events (ADEs) are a common complication of medical care resulting in high morbidity and medical expenditure. Population level estimates of outpatient ADEs are limited. Our objective was to provide national estimates and characterizations of outpatient ADEs and determine risk factors associated with these events. METHODS: Data are from the National Center for Health Statistics which collects information on patient visits to outpatient clinics and emergency departments throughout the United States. We examined visits between 1995 and 2005 and measured the national annual estimates of and risk factors for outpatient ADEs requiring medical treatment. RESULTS: The national annual number of ADE-related visits was 4 335,990 (95%CI: 4 326 872-4 345 108). Visits for ADEs to outpatient clinics increased over the study period from 9.0 to 17.0 per 1000 persons (p-value for trend < 0.001). In multivariate analyses, factors associated with ADE visits included patient age (OR: 2.13; 95%CI: 1.63-2.79 for 65 years and older), number of medications taken by patient (OR: 1.88; 95%CI: 1.58-2.25 for five medications or more), and female gender (OR: 1.51; 95%CI: 1.34-1.71). Overall, outpatient ADEs resulted in 107,468 (95%CI: 89 011-125 925) hospital admissions annually, with older patients at highest risk for hospitalization (p-value for trend < 0.001). CONCLUSIONS: Both patient age and polypharmacy use are risk factors for ADE-related healthcare visits, which have substantially increased in outpatient clinics between 1995 and 2005. The incidence of ADEs has particularly increased among patients 65 years and older with as many as 1 in 20 persons seeking medical care for an ADE.

Predisposition to epilepsy--does the ABCB1 gene play a role?

We performed a meta-analysis to evaluate the association between ABCB1 C3435T polymorphisms and the prevalence of epilepsy, including all relevant human studies (until June 2009), in which patients with or without epilepsy had undergone genotyping for the ABCB1 gene. Odds ratios (ORs) were calculated using a random effects model. We identified 9 case-control studies that included a total of 3,996 patients (2,454 with epilepsy and 1,542 nonepileptic subjects). No association was found between ABCB1 C3435T polymorphisms and the risk of having epilepsy (odds ratio 1.07, 95% confidence interval 0.76-1.51; p = 0.34). ABCB1 genotyping for epileptic patients is not warranted.

Pediatric adverse drug events in the outpatient setting: an 11-year national analysis.

OBJECTIVE: Adverse drug events (ADEs) are a common complication of medical care, but few pediatric data are available describing the frequency or epidemiology of these events. We estimated the national incidence of pediatric ADEs requiring medical treatment, described the pediatric population seeking care for ADEs, and characterized the events in terms of patient symptoms and medications implicated. METHODS: Data were obtained from the National Center for Health Statistics, which collects information on patient visits to outpatient clinics and emergency departments throughout the United States. We analyzed data for children 0 to 18 years of age seeking medical treatment for an ADE between 1995 and 2005. RESULTS: The mean annual number of ADE-related visits was 585922 (95% confidence interval [CI]: 503687-668156) of which 78% occurred in outpatient clinics and 12% occurred in emergency departments. Children 0 to 4 years of age had the highest incidence of ADE-related visits, accounting for 43.2% (95% CI: 35.6%-51.2%) of visits. The most common symptom manifestations were dermatologic conditions (45.4% [95% CI: 36.9%-54.1%]) and gastrointestinal symptoms (16.5% [95% CI: 11.1%-23.8%]). The medication classes most frequently implicated in an ADE were antimicrobial agents (27.5% [95% CI: 21.5%-34.5%]), central nervous system agents (6.5% [95% CI: 4.0%-10.5%]), and hormones (6.1% [95% CI: 3.1%-11.6%]). While ADEs related to antimicrobial agents were most common among children 0 to 4 years old and decreased in frequency among older children, ADEs resulting from central nervous system agents and hormones increased in frequency among children 5 to 11 and 12 to 18 years old. CONCLUSIONS: ADEs result in a substantial number of health care visits, particularly in outpatient clinics. The incidence of ADEs and medications implicated vary by age, indicating that age-specific approaches for monitoring and preventing ADEs may be most effective.

The effect of hospital bed occupancy on throughput in the pediatric emergency department.

STUDY OBJECTIVE: Although it has been suggested that high hospital occupancy leads to emergency department (ED) overcrowding and impedes ED throughput, there are limited data defining this relationship. The objective of this study is to examine whether high inpatient hospital occupancy negatively affects throughput in a pediatric ED. METHODS: This cross-sectional analysis evaluated patient visits to an urban pediatric ED and hospital occupancy rates. Data were collected from a 347-bed pediatric tertiary care hospital in Boston, MA, between January and December 2006. Primary outcome measure was ED length of stay; secondary outcomes were percentages of patients who left without being seen or had a hallway bed used for treatment. RESULTS: Throughout the study period, there were 56,335 patient visits to the pediatric ED; 9,687 (17%) patients were hospitalized. High hospital occupancy directly correlated with longer length of stay for all patients treated in the ED. When inpatient occupancy was at or more than 80% capacity, every 5% increase in hospital occupancy was associated with an increase in length of stay of 17.7 minutes for discharged patients (95% confidence interval [CI] 2.2 to 33.2 minutes) and 34.3 minutes for admitted patients (95% CI 11.4 to 57.2 minutes). With the same 5% increase in inpatient occupancy, there were increases in the odds of either a patient leaving without being seen (odds ratio 1.21; 95% CI 1.12 to 1.31) or being treated in a hallway bed (odds ratio 1.18; 95% CI 1.15 to 1.22). CONCLUSION: High hospital occupancy has a significant and quantifiable negative influence on ED throughput, affecting patients both discharged and hospitalized.

Glass table-related injuries in children.

OBJECTIVES: To investigate the patterns of injury sustained from glass table-related accidents to estimate whether tempered glass would prevent injuries. METHODS: We conducted a retrospective cohort analysis of all patients in an urban pediatric emergency department between October of 1995 and May for 2007 for glass table-related accidents. Data collected included age, sex, injury characteristics, examination findings, radiographic imaging, interventions, and disposition.We used a preventability score ranging from I (fully preventable injury with safety glass) to IV (unlikely to be preventable with safety glass). RESULTS: We identified 174 eligible patients during the study period. The median age was 3.4 years (interquartile range, 2.0-6.6 years); 62.1% were boys. The face was most commonly involved (45.6%) followed by lower (23.8%) and upper extremities (18.9%). Patients younger than 5 years were associated with more facial injuries (odds ratio, 6.0; 95% confidence interval, 2.9-12.6). Radiographs were obtained in 68 patients, and computed tomographic scans in 3 (total, 40.1%). Surgical repair was needed in 143 patients (82.1%), of whom 15 (10.5%) underwent procedural sedation and 8 (5.6%) required operative management. Reviewers ranked 74 patients (42.5%) as grade I, 20 patients (11.5%) as grade II, 64 patients (36.8%) as grade III, and 16 patients (9.2%) as grade IV. CONCLUSIONS: Glass table injuries are associated with significant morbidity. More than half of the injuries may have been prevented or mitigated with the use of tempered glass. Pediatricians are advised to discourage families from the purchase of nontempered glass tables, while advocating for legislation mandating the use of tempered glass.

"Left without being seen": a national profile of children who leave the emergency department before evaluation.

STUDY OBJECTIVE: The epidemiology of children who present to the emergency department (ED) and leave without being seen has not been well characterized. We evaluate rates and secular trends of children who leave without being seen, identify factors associated with pediatric leave without being seen cases, and determine whether there are differences in leaving patterns between children and adults seeking emergency care. METHODS: Data were obtained from the National Hospital Ambulatory Medical Care Survey, which collects information on patient visits to EDs throughout the United States. We examined data for children (less than or equal to 18 years of age) and adults who presented to EDs during the 6-year period ending in 2005. RESULTS: During the study period, there were an estimated 11,848,351 leave without being seen visits nationally, accounting for 1.79% of all ED visits. The prevalence of leaving without being seen was 2.46% (95% confidence interval [CI] 1.71% to 3.55%) for pediatric patients presenting to pediatric EDs, 1.86% (95% CI 1.65% to 2.10%) for pediatric patients presenting to general EDs, and 1.73% (95% CI 1.57% to 1.91%) for adults presenting to general EDs. The leave without being seen rates did not increase significantly during the study period. Factors associated with leave without being seen visits included hospital urban location, self-pay insurance status, and less acute triage level for children and adults, as well as race/ethnicity and arrival time for adult patients. CONCLUSION: In this national sample of patients, leave without being seen rates were similar for pediatric and adult patients and did not increase during the 6-year study period, although some variation in rates was observed for specific patient and ED characteristics. These national estimates provide an important reference for institutions to assess their ED performance.

Comparative analysis of zinc protoporphyrin and blood lead levels in lead-exposed Andean children.

OBJECTIVES: The objective of this study was to investigate the zinc protoporphyrin/heme ratio (ZPP/heme) as a biomarker for chronic lead (Pb) poisoning in children with a history of high Pb exposure. DESIGN AND METHODS: ZPP/heme ratio was measured in blood samples from 78 children (44 females and 34 males) with persistent Pb exposure from Pb glazing of ceramics in a local cottage industry in the Andes Mountains of Ecuador. RESULTS: Mean blood lead (PbB) level was 26.4 microg/dL (SD: 23.2; range: 4.0-107.0), and the mean ZPP/heme ratio was 152.4 micromol/mol (SD: 190.6; range: 36.0-1064.0). A regression analysis of PbB level and ZPP/heme ratio revealed a significant association (r=0.761, p= <0.0001), with the logZPP showing a higher correlation with PbB (r=0.869, p= <0.0001). The ZZP/heme ratio decreased significantly with increasing age (ANOVA, p=0.030). The mean ZPP/heme ratios for females and males were 139.6 and 169.0 micromol/mol, respectively, and were not statistically different (t-test, p=0.504). CONCLUSION: The elevated ZPP/heme ratios, coupled with high PbB levels observed in this cohort of Andean children of Pb-glazing workers, suggest chronic Pb intoxication and probable iron deficiency.

Emergency care for children in pediatric and general emergency departments.

OBJECTIVE: We examine the pediatric emergency department (ED) population and their clinical course in pediatric versus general EDs and identify potential factors contributing to differences in performance metrics between the 2 ED settings. METHODS: This was a retrospective analysis of pediatric visits to nationally representative EDs participating in the National Hospital Ambulatory Medical Care Survey from 1995 to 2002. Differences between pediatric and general EDs were examined in terms of patient characteristics and clinical course. RESULTS: Pediatric EDs treated more children with medical problems than general EDs, which treated more children with injuries. Visits by children to pediatric EDs were associated with longer wait times to see a physician (median, 40 vs. 25 minutes; P < 0.001) and longer stays in the ED (median, 130 vs. 98 minutes; P = 0.006). In multivariate analysis, the type of ED treating a pediatric patient was a significant determinant of wait time (percent change for pediatric EDs, 23.1; 95% confidence interval [CI], 3.4-46.6), length of stay (percent change for pediatric EDs, 23.0; 95% CI, 5.1-43.9), and rate of discharge (odds ratio for pediatric EDs, 0.75; 95% CI 0.61-0.92). Children in pediatric EDs seemed to be sicker than those in general EDs. CONCLUSIONS: These data provide the first glimpse of health care delivery to children seen in EDs nationally. Our findings indicate that significant differences exist between pediatric visits to pediatric and general EDs. These findings may be useful in establishing performance metrics for the care of ill and injured children in both pediatric and general EDs.

Environmental evaluation of a child with developmental disability.

Children's health can be affected adversely by the environment in which they live. It is well recognized that some environmental chemicals are harmful to the brain, but the role these chemicals play in the development of specific disabilities such as attention deficit hyperactivity disorder and autism is not certain. Parents of children who have developmental disabilities often ask the primary care physician whether certain environmental toxicants might be the cause of the illness. A detailed environmental history and physical examination may help clarify whether there is a plausible relationship between an environmental toxicant and a child's disability.

Transient psychosis in an immune-competent patient after oral trimethoprim-sulfamethoxazole administration.

We describe a rare adverse reaction to trimethoprim-sulfamethoxazole (TMP-SMX; Septra, Bactrim) in an immune-competent female adolescent. She was prescribed TMP-SMX for a urinary tract infection, which she had developed while being treated in the hospital for an extensive leg cellulitis. Shortly after receiving her third dose of TMP-SMX, she developed an acute altered mental status with agitation as well as vivid visual and auditory hallucinations. After prompt discontinuation of TMP-SMX, the patient slowly began to improve and was able to return to her baseline mental status within 10 days. No residual mental status changes were present. Despite the recent emergence of multidrug-resistant bacterial pathogens, TMP-SMX, one of the first-generation broad-spectrum antibiotics, continues to be widely prescribed, in part because of its low cost and its easy availability. It is generally well tolerated and is associated with relatively few adverse effects. More common toxicities associated with TMP-SMX include hypersensitivity reactions, bone marrow suppression, and gastrointestinal side effects. Central nervous system toxicity is very rare; when reported, it has been in an immune-compromised or an elderly patient.

Association of race/ethnicity with emergency department wait times.

OBJECTIVE: To determine whether wait times for children treated in emergency departments (EDs) nationally are associated with patient race/ethnicity. METHODS: Data were obtained from the National Hospital Ambulatory Medical Care Survey, which collects information on patient visits to EDs throughout the United States. We examined data for patients < or =15 years of age who presented to EDs during the 4-year period of 1997-2000. Sample weights were applied to the identified patient records to yield national estimates. For the purposes of this study, race/ethnicity was analyzed for 3 major groups, ie, non-Hispanic white (NHW), non-Hispanic black (NHB), and Hispanic white (HW). RESULTS: During the 4-year study period, 20633 patient visits were surveyed, representing a national sample of 92.9 million children < or =15 years of age. The race/ethnicity distribution included 9019 NHW children (59.5%), 3910 NHB children (23.9%), and 2991 HW children (16.6%). The wait time for all groups was 43.6 +/- 1.7 minutes (mean +/- SEM). There were significant unadjusted intergroup differences in wait times (38.5 +/- 1.6 minutes, 48.7 +/- 0.5 minutes, and 54.5 +/- 0.1 minutes for NHW, NHB, and HW children, respectively). Visit immediacy (triage status), when reported, was categorized as <15 minutes for 2203 children (17.1%), 15 to 60 minutes for 5324 (41.4%), 1 to 2 hours for 3010 (25.1%), and >2 to 24 hours for 1910 (16.4%). There were significant unadjusted differences in triage status according to race, with 14.6% of NHW patients being placed in the >2-hour immediacy range, compared with 18.8% of NHB patients and 20.0% of HW patients. In a linear regression analysis with logarithmically transformed wait time as a dependent variable and with adjustment for potential confounders, including hospital location, geographic region, and payer status, both NHB and HW patients waited longer than NHW patients, although the results were statistically significant only for HW patients. CONCLUSIONS: These nationally representative data suggest that children who come to EDs have wait times that vary according to race/ethnicity. There are several potential explanations for this observation, including discrimination, cultural incompetence, language barriers, and other social factors. These data and similar data from the National Hospital Ambulatory Medical Care Survey are useful in identifying nonclinical influences on the delivery of pediatric emergency care.

4-methylpyrazole decreases 1,4-butanediol toxicity by blocking its in vivo biotransformation to gamma-hydroxybutyric acid.

1,4-Butanediol (1,4-BD), a prodrug converted in vivo to gamma-hydroxybutyric acid by alcohol dehydrogenase, has resulted in life-threatening overdoses and deaths. We investigated whether 4-methylpyrazole (4-MP), an alcohol dehydrogenase antagonist, can be used as an antidote in a murine model of 1,4-BD overdose. CD-1 mice were overdosed with 1,4-BD, 600 mg/kg i.p. Mice then received 4-MP, 25 mg/kg i.p., or control injections after 1 min, 5 min, and symptom appearance. Mice were then evaluated for toxicity by the righting reflex and rotarod test every 10 min after intervention. When 4-MP was administered 1 and 5 min after 1,4-BD overdose, mice completely maintained their righting reflex. Conversely, control mice lost their righting reflex for 110 and 130 min, respectively (P < 0.05). When 4-MP was administered after symptomatic 1,4-BD overdose, mice lost their righting reflex but recovered it by 60 min. Conversely, control mice lost their righting reflex and recovered it by 140 min (P < 0.05). When 4-MP was administered at 1 min after 1,4-BD overdose, mice never failed the rotarod test. Conversely, control mice failed the rotarod test for 210 min (P < 0.05). When 4-MP was administered 5 min after 1,4-BD and after symptomatic 1,4-BD overdose, mice failed the rotarod test for 100 and 110 min, respectively. Conversely, control mice failed the rotarod test for 210 and 180 min, respectively (P < 0.05). In addition, treatment of mice with 4-MP significantly attenuated increases in blood gamma-hydroxybutyric acid concentrations and prevented loss of the righting reflex and failure of the rotarod test. In this murine model of 1,4-BD overdose, 4-MP conferred antidotal effects by inhibiting alcohol dehydrogenase-mediated biotransformation of 1,4-BD to gamma-hydroxybutyric acid.

Diagnosis of acute appendicitis in children using a clinical practice guideline.

PURPOSE: In October 2000, our institution implemented a clinical practice guideline (CPG) utilizing selective computed tomography (CT) and ultrasound scan (US) for the evaluation of children with suspected appendicitis. The authors sought to determine surgical outcomes and diagnostic accuracy in the CPG period. METHODS: The authors retrospectively analyzed the medical records of patients evaluated under the CPG at their institution between January 1 and December 31, 2001. Depending on a patient's clinical presentation, the CPG recommends immediate surgery or further evaluation with CT or US. CPG patients were identified if they received an appendectomy or a CT or US for suspected appendicitis. Negative appendectomy and perforation rates, as well as admissions for inpatient observation were compared with control patients treated for suspected appendicitis at our hospital in 1997, before frequent utilization of imaging studies. RESULTS: In the CPG period, 571 patients were evaluated for acute appendicitis, with 272 undergoing an appendectomy. Whereas 513 patients (90%) received a CT or US, only 34 patients (6%) were admitted to the surgical service for serial examinations. Patients with a histologically normal appendix decreased from 27 of 255 (10.6%) in 1997 to 15 of 272 (5.5%) in 2001 (P =.03). Fifty-seven patients (22.2%) in 2001 had a perforated appendix compared with 65 (28.5%) in 1997 (P =.11). The CPG, incorporating clinical judgment and selected imaging, had a sensitivity of 98.8%, a specificity of 95.2%, and positive and negative predictive values of 94.4% and 99.0%, respectively. CONCLUSIONS: A clinical practice guideline selectively utilizing CT and US is highly accurate in the diagnosis of acute appendicitis, minimizing the need for inpatient admission for serial examinations.

Succimer (meso-2,3-dimercaptosuccinic acid (DMSA)) treatment of Andean children with environmental lead exposure.

The authors studied children in Andean villages contaminated by a lead-glazing cottage industry. Mean blood lead (PbB) level in 35 exposed children, aged 3-14 years, a year before treatment, at the time of initiation of a comprehensive lead education and prevention program, was 53.4 microg/dL. PbB levels immediately before and three weeks after a ten-day regimen of succimer treatment of the 35 children were 43.4 microg/dL and 34.3 microg/dL, respectively, showing a 21% reduction and a significant difference between means (t = 5.09, p = 0.0001). PbB levels of the same children a year before treatment and immediately pre-treatment were also significantly different (t = 10.59, p = 0.0001). Thus, a ten-day course of succimer chelation effectively reduced PbB in children with moderate to severe Pb intoxication, and the education and prevention program, initiated with parents, health care providers, and educators, also contributed significantly to reducing PbB.

Adult patient visits to children's hospital emergency departments.

BACKGROUND: Adults frequently seek medical services in children's hospital emergency departments (CHEDs), and are required to be admitted to CHEDs under the provisions of the Emergency Medical Transfer and Active Labor Act (EMTALA), which requires medical evaluation and stabilization of every patient who presents to an emergency department. In recent years visits by adults to CHEDs appear to have increased. OBJECTIVE: There were 3 objectives to the current study: 1) to examine secular trends in the number of adult patients visiting CHEDs, 2) to determine if perceived increases are related to the implementation of EMTALA, and 3) to examine the characteristics, evaluation, and disposition of adult patients presenting for first-time visits to a CHED. METHODS: A database of all visits to an urban CHED between 1992 and 2002 was queried to collect information on adult patients (22 years or older). New adult patients were identified based on the assignment of new medical record numbers. The medical records of all adult patients presenting during the 1-year interval before and after the institution's full implementation of EMTALA were reviewed and relevant data collected. RESULTS: Over the study period, there were 501,033 patient visits to the CHED. Of these, 5512 (1.1%) were by adult patients, which included 536 (9.7%) new adult patients. Using the chi(2), test we found a significant increase in the total number of adult visits and the number of new adult visits, particularly after the implementation of EMTALA. The mean age of the new adult patients was 34.9 +/- 11.9 years. Their most frequent chief complaints were injuries (24.4%), cardiac-related problems (7.6%), and syncope (6.7%). A total of 427 (79.7%) of the new adult patients were treated and released, 81 (15.1%) were transferred to an outside hospital for additional care, and 15 (2.8%) were admitted to our hospital. There were no significant differences between the new adult populations in 1997 and 1999. Comparing new and established adult populations in 1999, the population of new adults was significantly older (28.1 +/- 6.8 vs 34.9 +/- 11.9 years) and more likely to present with injuries or syncopal episodes. Among the total cohort of new adult patients in the study, chest pain also occurred at a significantly higher rate compared with established adults (6.7% vs 3.8%). CONCLUSIONS: Adult visits to CHEDs appear to be increasing in frequency in association with the implementation of EMTALA regulations. It is therefore essential that physicians staffing CHEDs be properly trained in the stabilization of common adult medical emergencies. We recommend that the language of EMTALA be revised to allow adult patients with nonemergent problems to be directly referred to adult emergency departments, which are more appropriate than CHEDs.