Estimating prevalence of overweight or obese children and adolescents in small geographic areas using publicly available data.

INTRODUCTION: Interventions for pediatric obesity can be geographically targeted if high-risk populations can be identified. We developed an approach to estimate the percentage of overweight or obese children aged 2 to 17 years in small geographic areas using publicly available data. We piloted our approach for Georgia. METHODS: We created a logistic regression model to estimate the individual probability of high body mass index (BMI), given data on the characteristics of the survey participants. We combined the regression model with a simulation to sample subpopulations and obtain prevalence estimates. The models used information from the 2001-2010 National Health and Nutrition Examination Survey, the 2010 Census, and the 2010 American Community Survey. We validated our results by comparing 1) estimates for adults in Georgia produced by using our approach with estimates from the Centers for Disease Control and Prevention (CDC) and 2) estimates for children in Arkansas produced by using our approach with school examination data. We generated prevalence estimates for census tracts in Georgia and prioritized areas for interventions. RESULTS: In DeKalb County, the mean prevalence among census tracts varied from 27% to 40%. For adults, the median difference between our estimates and CDC estimates was 1.3 percentage points; for Arkansas children, the median difference between our estimates and examination-based estimates data was 1.7 percentage points. CONCLUSION: Prevalence estimates for census tracts can be different from estimates for the county, so small-area estimates are crucial for designing effective interventions. Our approach validates well against external data, and it can be a relevant aid for planning local interventions for children.

A general approach to site-specific antibody drug conjugates.

Using an expanded genetic code, antibodies with site-specifically incorporated nonnative amino acids were produced in stable cell lines derived from a CHO cell line with titers over 1 g/L. Using anti-5T4 and anti-Her2 antibodies as model systems, site-specific antibody drug conjugates (NDCs) were produced, via oxime bond formation between ketones on the side chain of the incorporated nonnative amino acid and hydroxylamine functionalized monomethyl auristatin D with either protease-cleavable or noncleavable linkers. When noncleavable linkers were used, these conjugates were highly stable and displayed improved in vitro efficacy as well as in vivo efficacy and pharmacokinetic stability in rodent models relative to conventional antibody drug conjugates conjugated through either engineered surface-exposed or reduced interchain disulfide bond cysteine residues. The advantages of the oxime-bonded, site-specific NDCs were even more apparent when low-antigen-expressing (2+) target cell lines were used in the comparative studies. NDCs generated with protease-cleavable linkers demonstrated that the site of conjugation had a significant impact on the stability of these rationally designed prodrug linkers. In a single-dose rat toxicology study, a site-specific anti-Her2 NDC was well tolerated at dose levels up to 90 mg/kg. These experiments support the notion that chemically defined antibody conjugates can be synthesized in commercially relevant yields and can lead to antibody drug conjugates with improved properties relative to the heterogeneous conjugates formed by nonspecific chemical modification.

Restoration of leptin responsiveness in diet-induced obese mice using an optimized leptin analog in combination with exendin-4 or FGF21.

The identification of leptin as a mediator of body weight regulation provided much initial excitement for the treatment of obesity. Unfortunately, leptin monotherapy is insufficient in reversing obesity in rodents or humans. Recent findings suggest that amylin is able to restore leptin sensitivity and when used in combination with leptin enhances body weight loss in obese rodents and humans. However, as the uniqueness of this combination therapy remains unclear, we assessed whether co-administration of leptin with other weight loss-inducing hormones equally restores leptin responsiveness in diet-induced obese (DIO) mice. Accordingly, we report here the design and characterization of a series of site-specifically enhanced leptin analogs of high potency and sustained action that, when administered in combination with exendin-4 or fibroblast growth factor 21 (FGF21), restores leptin responsiveness in DIO mice after an initial body weight loss of 30%. Using either combination, body weight loss was enhanced compared with either exendin-4 or FGF21 monotherapy, and leptin alone was sufficient to maintain the reduced body weight. In contrast, leptin monotherapy proved ineffective when identical weight loss was induced by caloric restriction alone over a comparable time. Accordingly, we find that a hypothalamic counter-regulatory response to weight loss, assessed using changes in hypothalamic agouti related peptide (AgRP) levels, is triggered by caloric restriction, but blunted by treatment with exendin-4. We conclude that leptin re-sensitization requires pharmacotherapy but does not appear to be restricted to a unique signaling pathway. Our findings provide preclinical evidence that high activity, long-acting leptin analogs are additively efficacious when used in combination with other weight-lowering agents.

Adverse effects of oral nonstimulant psychotropic medications in young children reported to a regional poison center.

BACKGROUND: Use of nonstimulant psychotropic medications other than antidepressants in young children is reported to be increasing. The patient safety ramifications of this remain unclear. OBJECTIVES: To evaluate the frequency of calls to a regional poison center reporting adverse drug effects and the level of medical attention required in young children who are receiving oral nonstimulant psychotropic medications. MATERIALS AND METHODS: A retrospective review of 544 267 consecutive human exposure poison center records between 2000 and 2008 was conducted for cases of young children given nonstimulant psychotropic medications with therapeutic intent. RESULTS: A total of 597 cases met criteria for analysis. Drugs involved were 286 risperidone, 133 clonidine, 114 quetiapine, 37 aripiprazole, 43 olanzapine, 29 ziprasidone, and 5 buspirone; two or more were involved in 250 cases. Reasons for exposure included excess dose given unintentionally (61%), wrong medication unintentionally (12%), adverse effects with correct dose (11%), excess dose intentionally (0.6%), therapeutic error by health-care provider (0.5%), and unclear circumstances (15%). Moderate effects (such as dystonic reaction) occurred in 34 patients at their usual dose (53% of 64) and in 15 at unintentionally excessive doses (4% of 361). Emergency department evaluation of 22% of the children resulted in 5% of the total being admitted to a non-intensive care unit (ICU) bed and 2% of all admitted to an ICU bed. CONCLUSION: Dosing errors and adverse effects involving nonstimulant psychotropic medications are cause for concern in young children. Additional information about safety and optimal dosage of these medications is needed to guide appropriate use.

Physician practice variation in the pediatric emergency department and its impact on resource use and quality of care.

OBJECTIVE: To evaluate variation in case-mix adjusted resource use among pediatric emergency department (ED) physicians and its correlation with ED length of stay (LOS) and return rates. METHODS: Resource use patterns at 2 EDs for 36 academic physicians (163,669 patients at ED1) and 45 private physicians (289,199 patients at ED2) from 2003 to 2006 were abstracted for common laboratory tests, imaging studies, intravenous therapy (fluids/antibiotics), LOS and 72-hour return rate for discharged patients, and hospital admissions for all patients. Case-mix adjustment was based on triage acuity, diagnostic category, demographics, and temporal measures. OUTCOME MEASURES: (1) adjusted overall resource use for ED1 and ED2 physicians and (2) observed-to-expected ratios for ED1 physicians. RESULTS: Case-mix adjusted hospital admission rates among physicians varied nearly 3-fold (6.3%-18%) for ED1 and 8-fold (2.5%-19.4%) for ED2. Intravenous therapy use varied 2-fold (4.9%-10.4%) at ED1 and 3-fold (3.6%-11.4%) at ED2. Emergency department 2 physicians had an almost 2-fold (10.9%-20.6%) variation in imaging use. Variation in head computed tomography use was 2-fold (1.1%-2.5%) at ED1 and 5-fold (0.9%-4.8%) at ED2. Physicians had longer than expected LOS if they had higher than expected use of laboratory tests (r, 0.41; 95% confidence interval [CI], 0.09-0.65; P < 0.05) and imaging (r, 0.48; 95% CI, 0.17-0.69; P < 0.01). Return rate was not significantly correlated with resource use in any category. Physicians with higher than expected use of laboratory tests had higher than expected use of imaging (r, 0.62; 95% CI, 0.36-0.78; P < 0.001), head computed tomography (r, 0.49; 95% CI, 0.19-0.70; P < 0.01), and intravenous therapy (r, 0.51; 95% CI, 0.20-0.71; P < 0.01). CONCLUSIONS: Significant variation exists in physician use of common ED resources. Higher resource use was associated with increased LOS but did not reduce return to ED. Practice variation such as this may represent an opportunity to improve health care quality and decrease costs.

A randomized clinical trial of lidocaine gel for reducing infant distress during urethral catheterization.

OBJECTIVES: The purpose of this study was to determine whether a lidocaine-enhanced lubricant that was used topically and instilled into the urethra decreased infants' distress that was associated with catheterization. METHODS: Eligible study participants were febrile 2- to 24-month-old pediatric emergency department patients in need of a catheter-obtained urinalysis. Patients were randomly assigned to 1 of 3 groups. Patients had catheterization performed after a 4-minute protocol that included a topical lubricant control, topical and intraurethral lubricants, or topical and intraurethral lidocaines. All patients were filmed during the procedure and evaluated at 3 phases: the start of the study, time of instillation, and at the time of maximal catheter insertion. The 3 phases were analyzed by blinded coders using the Modified Behavioral Pain Scale. RESULTS: A total of 45 patients were enrolled in 1 of the 3 study groups. Patients who received lidocaine had a lower overall distress at a level approaching significance at the time of catheterization (phase 3; P = 0.065) and a significantly lower distress as measured by crying during the catheterization (phase 3; P = 0.036) than infants who did not have a lubricant instilled into the urethra. CONCLUSIONS: The use of topical and intraurethral lidocaine resulted in a lower distress when compared with a topical lubricant, at a level approaching significance for global distress. When a subsection of the total distress score that measured infant cry was evaluated, the difference between the intraurethral lidocaine group and the group without intraurethral instillation was statistically significant. Although the results are promising, intraurethral lidocaine did not fully alleviate discomfort associated with urethral catherization. The use of lidocaine is suggested for pediatric patients undergoing urethral catherization; however, evaluation of additional agents and techniques for further decreasing pain is also warranted.

Pediatric procedural sedation by a dedicated nonanesthesiology pediatric sedation service using propofol.

OBJECTIVES: To evaluate the success and dosing requirements of propofol in children for prolonged procedural sedation by a nonanesthesiology-based sedation service. METHODS: The pediatric sedation service at this institution uses propofol as its preferred sedative, and the local guideline suggests using 3 mg/kg for induction and 5 mg kg(-1) h(-1) for maintenance sedation. Doses can be adjusted as needed to individualize successful sedation. A retrospective analysis of patients sedated for 30 minutes or longer was conducted. Patients were stratified into 4 cohorts based on age (<1 year [n = 16], 1-2 years [n = 85], 3-7 years [n = 54], and >7 years [n = 55]) and dosing patterns, success, and adverse effects were investigated. RESULTS: Two hundred forty-nine patients met the inclusion criteria. Mean age was 4.8 years (SD, 4.1). The mean induction dose was 3.2 mg/kg (range, 0.9-9.7), and the mean maintenance infusion was 5.2 mg kg(-1) h(-1) (range, 0.14-21.3). No differences were seen in the induction doses in the different age cohorts, yet the SD was largest in the youngest cohort compared to any other. Although no differences were seen in maintenance rates by age, the greatest SD for dosing was seen in the oldest cohort. For all ages, all sedations were successful (100%) and unanticipated adverse effects rare (<1%). CONCLUSIONS: Although it seems that the mean dosing of propofol does not vary significantly with age, there is greater variability in induction dosage for those younger than 1 year and in maintenance dosing for those 7 years or older. The results and general dosing parameters may assist pediatric subspecialists in using propofol for prolonged procedural sedation.

Pediatric emergency department overcrowding: electronic medical record for identification of frequent, lower acuity visitors. Can we effectively identify patients for enhanced resource utilization?

The objective of this study was to utilize the electronic medical record system to identify frequent lower acuity patients presenting to the Pediatric Emergency Department and to evaluate their impact on Pediatric Emergency Department overcrowding and resource utilization. The electronic medical records (EMR) of two pediatric emergency centers were reviewed from August 2002 to November 2004. Pediatric Emergency Department encounters that met any of the following criteria were classified as Visits Necessitating Pediatric Emergency Department care (VNEC): Disposition of admission, transfer or deceased; Intravenous fluids (IVF) or medications (excluding single antipyretic or antihistamine); Radiology or laboratory tests (excluding Rapid Strep); Fractures, dislocations, and febrile seizures. All other visits were classified as non-VNEC. ICD-9 (International Classification of Diseases, Ninth Revision) codes from the Pediatric Emergency Department encounters were defined as representing chronic or non-chronic conditions. Patients were then evaluated for utilization patterns, frequency of Emergency Department (ED) visits, chronic illness, and VNEC status. There were 153,390 patients identified, representing 255,496 visits (1.7 visits/patient, range 1-49). Overall, 189,998 visits (74%) required defined ED services and were categorized as VNEC, with the remaining 65,498 visits (26%) categorized as non-VNEC. With increasing visits, a steady decline in those requiring ED services was observed, with a plateau by visit six (VNEC 77% @ one visit, 64% @ six visits, p < 0.001). There were 141,765 patients seen fewer than four times, representing 92% of the patients and 74% of all visits (1.3 visits/patient, 225 visits/day). In contrast, 2664 patients disproportionately utilized the ED more than six times (maximum 49), representing 1.7% of patients and 9.8% of visits (9.4 visit/patient, 30 visits/day, p < 0.001). Excluding patients with chronic illness, 1074 patients also disproportionately utilized the ED more than six times (maximum 28), representing 0.7% of patients and 3.6% of visits (8.6 visit/patient, 11 visits/day, p < 0.001). While representing < 2% of patients, frequent lower acuity utilizers of ED services accounted for nearly 10% of all visits (30/day). Low acuity patients may require only limited additional marginal resources for their individual care. However, in aggregate, inefficiencies occur, especially when systems reach capacity constraints, at which point these patients utilize limited resources (manpower and space) that could more effectively be directed toward the more acutely ill and injured patients. Therefore, identification of these patients utilizing the electronic medical record will allow for targeted interventions of this subgroup to improve future resource allocation.

B-type natriuretic peptide in the emergency diagnosis of critical heart disease in children.

OBJECTIVE: The initial presentation of congenital and acquired heart disease in children can present a diagnostic challenge. We sought to evaluate B-type natriuretic peptide as a marker of critical heart disease in children at presentation in the acute care setting. METHODS: A cohort of 33 pediatric patients with newly diagnosed congenital or acquired heart disease had B-type natriuretic peptide levels obtained on hospital admission after evaluation in an acute care setting. Patients were admitted from March 2005 through February 2007. A noncardiac cohort of 70 pediatric patients who presented with respiratory or infectious complaints had B-type natriuretic peptide levels obtained during emergency department evaluation. A comparison of B-type natriuretic peptide results was performed. RESULTS: Cardiac diagnoses included cardiomyopathy (14), left-sided obstructive lesions (12), anomalous left coronary artery from the pulmonary artery (4), total anomalous pulmonary venous return (2), and patent ductus arteriosus (1). Cardiac cohort mean age at presentation was 33.6 months. The 33 patients with new cardiac diagnoses had a mean B-type natriuretic peptide level of 3290 pg/mL (SD: +/-1609; range: 521 to >5000 pg/mL). The 70 noncardiac patients' mean age at presentation was 23.1 month, and mean B-type natriuretic peptide level was 17.4 pg/mL (SD: +/-20; range: <5 to 174 pg/mL). CONCLUSIONS: B-type natriuretic peptide levels were markedly elevated at presentation in the acute care setting for all patients in this cohort of children with newly diagnosed congenital or acquired heart disease. B-type natriuretic peptide levels from noncardiac patients were significantly lower, with no overlap to the cardiac disease group. B-type natriuretic peptide level can be useful as a diagnostic marker to aid in the recognition of pediatric critical heart disease in the acute care setting.

CT versus plain radiographs for evaluation of c-spine injury in young children: do benefits outweigh risks?

BACKGROUND: Various reports support the use of cervical spine (c-spine) CT over conventional radiography in screening of c-spine injury. Interest now exists in diagnostic radiation-induced morbidity. OBJECTIVE: To estimate excess relative risk for developing cancer from c-spine high-resolution CT radiation exposure. MATERIALS AND METHODS: We conducted a retrospective review of children evaluated for c-spine injury using CT. The study population was divided into three age groups, 0-4 years (group 1), 5-8 years (group 2), and older than 8 years (group 3). Anthropomorphic 1-year-old and 5-year-old phantoms were used to measure radiation at the thyroid during radiography and CT. Excess relative risk for thyroid cancer was estimated using these measurements. RESULTS: A total of 557 patients were evaluated with CT. The radiographic method most commonly used was head CT/c-spine CT in 363 (65%). Only 179 children (32%) had any type of prior radiography. The use of c-spine CT exposes the thyroid to 90-200 times more radiation than multiple conventional radiographs. The mean excess relative risk for thyroid cancer after CT was 2.0 for group 1 and 0.6 for group 2. There were no comparison data for group 3. CONCLUSION: C-spine CT is associated with a significant exposure to ionizing radiation and increases excess relative risk for thyroid cancer in young children.

Evaluation of a pediatric-sedation service for common diagnostic procedures.

BACKGROUND: Pediatric patients often require sedation for diagnostic procedures such as magnetic resonance imaging and computed tomography scanning. In October 2002, a dedicated sedation service was started at a tertiary care pediatric facility as a joint venture between pediatric emergency medicine and pediatric critical care medicine. Before this service, sedation was provided by the department of radiology by using a standard protocol, with high-risk patients and failed sedations referred for general anesthesia. OBJECTIVES: To describe the initial experience with a dedicated pediatric-sedation service. METHODS: This was a retrospective analysis of quality-assurance data collected on all sedations in the radiology department for 23-month periods before and after sedation-service implementation. Study variables were number and reasons for canceled or incomplete procedures, rates of referral for general anesthesia, rates of hypoxia, prolonged sedation, need for assisted ventilation, apnea, emesis, and paradoxical reaction to medication. Results are reported in odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS: Data from 5,444 sedations were analyzed; 2,148 before and 3,296 after sedation-service activation. Incomplete studies secondary to inadequate sedation decreased, from 2.7% before the service was created to 0.8% in the post-sedation-service period (OR, 0.29; 95% CI = 0.18 to 0.47). There also were decreases in cancellations caused by patient illness (3.8% vs. 0.6%; OR, 0.16; 95% CI = 0.10 to 0.27) and rates of hypoxia (8.8% vs. 4.6%; OR, 0.50; 95% CI = 0.40 to 0.63). There were no significant differences between the groups in rates of apnea, need for assisted ventilation, emesis, or prolonged sedation. The implementation of the sedation service also was associated with a decrease in both the number of patients referred to general anesthesia without a trial of sedation (from 2.1% to 0.1%; OR, 0.33; 95% CI = 0.06 to 1.46) and the total number of general anesthesia cases in the radiology department (from 7.5% to 4.4% of all patients requiring either sedation or anesthesia; OR, 0.56; 95% CI = 0.45 to 0.71). CONCLUSIONS: The implementation of a dedicated pediatric-sedation service resulted in fewer incomplete studies related to inadequate sedation, in fewer canceled studies secondary to patient illness, in fewer referrals for general anesthesia, and in fewer recorded instances of sedation-associated hypoxia. These findings have important implications in terms of patient safety and resource utilization.

A randomized, controlled trial of sucrose analgesia in infants younger than 90 days of age who require bladder catheterization in the pediatric emergency department.

OBJECTIVES: To determine whether an oral sucrose solution improves pain response for infants undergoing bladder catheterization in an emergency department (ED) population. METHODS: A randomized, double-blinded study comparing the analgesic effects of a sucrose solution to placebo for infants < or = 90 days of age and requiring bladder catheterization. Infants with prior bladder catheterization, previous painful procedures that day, or neurological or genital abnormalities were excluded. Infants were assigned baseline pain scores and then given 2 mL of sucrose or water 2 minutes before catheterization. Trained pediatric ED nurses rated the infants for pain, presence of cry, and time to return to baseline. RESULTS: Eighty-three patients were enrolled; 40 were randomized to sucrose, and 40, to placebo. Baseline pain scores were similar within each age group. Overall, sucrose did not produce a significant analgesic effect. In subgroup analysis, infants 1-30 days of age receiving sucrose showed a smaller change in pain scores (2.9 vs. 5.3, p = 0.035), were less likely to cry with catheterization (29% vs. 72%, p = 0.008), and returned to baseline more rapidly after catheter removal (10 seconds vs. 37 seconds, p = 0.04) compared with infants who received placebo. Infants older than 30 days of age who received sucrose did not show statistically significant differences in pain scores, crying, or time to return to baseline behavior. CONCLUSIONS: There was no overall treatment effect when using an oral sucrose solution before bladder catheterization in infants younger than 90 days of age. However, infants younger than or equal to 30 days of age who received sucrose had smaller increases in pain scores, less crying, and returned to baseline more rapidly than infants receiving placebo. Older infants did not show an improved pain response with oral sucrose.

Posttraumatic stress responses in children: awareness and practice among a sample of pediatric emergency care providers.

BACKGROUND: Research suggests that up to 4 of 5 children experience symptoms of an acute stress response (ASR) after a motor vehicle-related injury, and approximately 25% will develop posttraumatic stress disorder (PTSD). The degree to which physicians recognize this problem has not been reported. Our objective was to evaluate current awareness and practices of a cohort of pediatric emergency care providers regarding posttraumatic stress in children. METHODS: Participants were identified from a list of the American Academy of Pediatrics Section on Emergency Medicine and surveyed on their awareness of ASR after motor vehicle-related injury, risk factors for developing PTSD, and practices regarding emergency department (ED) interventions. Surveys from physicians not practicing clinical emergency medicine were excluded. RESULTS: Of 322 surveys returned, 287 responses met inclusion criteria. Among these respondents, 198 (69%) were pediatric emergency medicine board certified or eligible and 260 (91%) practiced in a designated pediatric ED. Only 20 of 287 respondents (7%) believed that children were likely to develop symptoms of posttraumatic stress at levels previously described. Also in contrast to recent literature, 248 respondents (86%) felt that severity of injury was associated with future development of PTSD. Associated parental injury was identified accurately as a risk factor by 250 respondents (87%). Of interest, only 31 respondents (11%) were aware of any available tools to assess risk for PTSD. In addition, 56 of 287 respondents (20%) indicated that they would not use such tools in the ED, most commonly citing time and cost constraints. Finally, only 52 respondents (18%) reported giving any verbal guidance and only 9 (3%) provided any written instructions about posttraumatic stress to their patients and families. CONCLUSIONS: Findings suggest that physicians underestimate the likely development of an ASR and PTSD in the pediatric population. At present, few physicians offer written or even verbal instruction related to the development of posttraumatic symptoms. Physician education along with a systematic approach of assessment and intervention is necessary to address the gap between underrecognition of this concern and desired clinical practice.

Pediatric restraint use is associated with reduced transports by emergency medical services providers after motor vehicle crashes.

OBJECTIVE: To determine the association between pediatric restraint use during motor vehicle crashes and patient transports by emergency medical services (EMS) providers. METHODS: Children under 16 years of age who were involved in motor vehicle crashes in Houston or Harris County, Texas, in 1997 were identified from Texas Department of Public Safety (DPS) crash data. DPS data were linked probabilistically to City of Houston Fire Department EMS data to identify whether the children were transported from the scene by EMS. Odds ratios were calculated to determine the association between restraint use and EMS transport. Logistic regression was used to control for age and injury severity in this relationship. RESULTS: From the linked data for 1997, 1,696 children were involved in reported automobile or truck crashes to which EMS responded. Of the 1,580 children about whom information concerning restraint use was available, 1,309 (83%) were wearing some type of safety restraint and 1,342 (85%) were transported by EMS. Adjusting for injury severity, children wearing safety restraints during motor vehicle crashes were 60% (95% confidence interval 34-75%) less likely to be transported by EMS than those not wearing safety restraints during such crashes. CONCLUSIONS: The use of safety restraints during motor vehicle crashes is associated with a reduction in the number of children transported from the scene by EMS providers. This effect is independent of age and injury severity.