Peter F. Ehrlich

Identifying Children at Very Low Risk of Clinically Important Blunt Abdominal Injuries

STUDY OBJECTIVE We derive a prediction rule to identify children at very low risk for intra-abdominal injuries undergoing acute intervention and for whom computed tomography (CT) could be obviated. METHODS We prospectively enrolled children with blunt torso trauma in 20 emergency departments. We used binary recursive partitioning to create a prediction rule to identify children at very low risk of intra-abdominal injuries undergoing acute intervention (therapeutic laparotomy, angiographic embolization, blood transfusion for abdominal hemorrhage, or intravenous fluid for ≥2 nights for pancreatic/gastrointestinal injuries). We considered only historical and physical examination variables with acceptable interrater reliability. RESULTS We enrolled 12,044 children with a median age of 11.1 years (interquartile range 5.8, 15.1 years). Of the 761 (6.3%) children with intra-abdominal injuries, 203 (26.7%) received acute interventions. The prediction rule consisted of (in descending order of importance) no evidence of abdominal wall trauma or seat belt sign, Glasgow Coma Scale score greater than 13, no abdominal tenderness, no evidence of thoracic wall trauma, no complaints of abdominal pain, no decreased breath sounds, and no vomiting. The rule had a negative predictive value of 5,028 of 5,034 (99.9%; 95% confidence interval [CI] 99.7% to 100%), sensitivity of 197 of 203 (97%; 95% CI 94% to 99%), specificity of 5,028 of 11,841 (42.5%; 95% CI 41.6% to 43.4%), and negative likelihood ratio of 0.07 (95% CI 0.03 to 0.15). CONCLUSION A prediction rule consisting of 7 patient history and physical examination findings, and without laboratory or ultrasonographic information, identifies children with blunt torso trauma who are at very low risk for intra-abdominal injury undergoing acute intervention. These findings require external validation before implementation.

Dose-Intensive Response-Based Chemotherapy and Radiation Therapy for Children and Adolescents With Newly Diagnosed Intermediate-Risk Hodgkin Lymphoma: A Report From the Children's Oncology Group Study AHOD0031

PURPOSE The Childrens Oncology Group study AHOD0031, a randomized phase III study, was designed to evaluate the role of early chemotherapy response in tailoring subsequent therapy in pediatric intermediate-risk Hodgkin lymphoma. To avoid treatment-associated risks that compromise long-term health and to maintain high cure rates, dose-intensive chemotherapy with limited cumulative doses was used. PATIENTS AND METHODS Patients received two cycles of doxorubicin, bleomycin, vincristine, etoposide, cyclophosphamide, and prednisone (ABVE-PC) followed by response evaluation. Rapid early responders (RERs) received two additional ABVE-PC cycles, followed by complete response (CR) evaluation. RERs with CR were randomly assigned to involved-field radiotherapy (IFRT) or no additional therapy; RERs with less than CR were nonrandomly assigned to IFRT. Slow early responders (SERs) were randomly assigned to receive two additional ABVE-PC cycles with or without two cycles of dexamethasone, etoposide, cisplatin, and cytarabine (DECA). All SERs were assigned to receive IFRT. RESULTS Among 1,712 eligible patients, 4-year event-free survival (EFS) was 85.0%: 86.9% for RERs and 77.4% for SERs (P < .001). Four-year overall survival was 97.8%: 98.5% for RERs and 95.3% for SERs (P < .001). Four-year EFS was 87.9% versus 84.3% (P = .11) for RERs with CR who were randomly assigned to IFRT versus no IFRT, and 86.7% versus 87.3% (P = .87) for RERs with positron emission tomography (PET) -negative results at response assessment. Four-year EFS was 79.3% versus 75.2% (P = .11) for SERs who were randomly assigned to DECA versus no DECA, and 70.7% versus 54.6% (P = .05) for SERs with PET-positive results at response assessment. CONCLUSION This trial demonstrated that early response assessment supported therapeutic titration (omitting radiotherapy in RERs with CR; augmenting chemotherapy in SERs with PET-positive disease). Strategies directed toward improved response assessment and risk stratification may enhance tailoring of treatment to patient characteristics and response.

Children's Oncology Group's 2013 blueprint for research: renal tumors.

Renal malignancies are among the most prevalent pediatric cancers. The most common is favorable histology Wilms tumor (FHWT), which has 5‐year overall survival exceeding 90%. Other pediatric renal malignancies, including anaplastic Wilms tumor, clear cell sarcoma, malignant rhabdoid tumor, and renal cell carcinoma, have less favorable outcomes. Recent clinical trials have identified gain of chromosome 1q as a prognostic marker for FHWT. Upcoming studies will evaluate therapy adjustments based on this and other novel biomarkers. For high‐risk renal tumors, new treatment regimens will incorporate biological therapies. A research blueprint, viewed from the perspective of the Childrens Oncology Group, is presented. Pediatr Blood Cancer 2013; 60: 994–1000.

US Estimates of Hospitalized Children With Severe Traumatic Brain Injury: Implications for Clinical Trials

Objectives: To estimate sample sizes available for clinical trials of severe traumatic brain injury (TBI) in children, we described the patient demographics and hospital characteristics associated with children hospitalized with severe TBI in the United States. Methods: We analyzed the 2006 Kids’ Inpatient Database. Severe TBI hospitalizations were defined as children discharged with TBI who required mechanical ventilation or intubation. Types of high-volume severe TBI hospitals were categorized based on the numbers of discharged patients with severe TBI in 2006. National estimates of demographics and hospital characteristics were calculated for pediatric severe TBI. Simulation analyses were performed to assess the potential number of severe TBI cases from randomly selected hospitals for inclusion in future clinical trials. Results: The majority of children with severe TBI were discharged from either a children’s unit in general hospitals (41%) or a nonchildren’s hospital (34%). Less than 5% of all hospitals were high-volume TBI hospitals, which discharged >78% of severe TBI cases and were more likely to be a children’s unit in a general hospital or a children’s hospital. Simulation analyses indicate that there is a saturation point after which the benefit of adding additional recruitment sites decreases significantly. Conclusions: Children with severe TBI are infrequent at any one hospital in the United States, and few hospitals treat large numbers of children with severe TBI. To effectively plan trials of therapies for severe TBI, much attention has to be paid to selecting the right types of centers to maximize enrollment efficiency.

Traumatic cervical spine injuries: characteristics of missed injuries

PURPOSE Computed tomographic (CT) scanning has mostly replaced x-rays as an imaging modality, but concerns exist because of excess radiation, missed injuries, and whether it is the definitive procedure for intubated patients. The purpose of this study was to characterize missed cervical spine injuries (CSIs). METHODS All pediatric (<18) trauma patients from 2004 to 2006 were analyzed. Age, sex, Injury Severity Score (ISS), mechanism, time, and missed injuries were reviewed. Flexion/extension views were used in patients with prolonged intubation. Descriptive statistics, chi(2), Students t test, and bivariate correlation were used. RESULTS There were 1307 pediatric trauma patients admitted with 318 imaged for potential CSI. Computed tomography was the sole imaging study in 200, x-rays in 64, and both in 54. Time to C-spine clearance was similar for all modalities (P > .05). For CT, 34 (10.7%) were initially positive for CSI with 7 false-positives (FPs) and no false-negative (FN). There were 18 patients with CSI identified by x-ray, with 5 FPs and 5 FNs (missed injuries). The 5 FNs missed by x-ray were all positive by CT scan and required no intervention. None of the flexion/extension views revealed an additional injury. Sex, intubated patients, ISS, age, type, and injury location were not predictive of a missed injury (P > .05).The sensitivity of CT scan was 1.0, specificity was 0.976, and the positive predictive value was 79.4%. The sensitivity of plain x-ray was 61.5%, the specificity was 1.6%, and the positive predictive value was 61.5%. CONCLUSIONS Our data suggest that CT scans should be the primary modality to image a CSI. Flexion/extension views did not add to the decision making for C-spine clearance after CT evaluation.

Clinicopathologic Findings Predictive of Relapse in Children With Stage III Favorable-Histology Wilms Tumor

PURPOSE Stage III designation in NWTS-5 (National Wilms Tumor Study-5) was determined by four pathologic criteria: positive lymph nodes (LNs), peritoneal implants, residual disease, and tumor rupture. The objective of this study was to determine the prognostic significance of each of the stage III criteria. PATIENTS AND METHODS Children with stage III Wilms tumor (WT) treated in NWTS-5 were assessed for event-free (EFS) and overall survival (OS). Sites of relapse and molecular status of tumors are reported. EFS and OS are reported 8 years after diagnosis. RESULTS There were 569 patients with local stage III favorable-histology (FH) WT in this analysis, of whom 109 had overall stage IV disease. LN involvement alone was the most frequent criterion for stage III designation (38%), followed by microscopic residual disease alone (20%), microscopic residual disease and LN involvement (14%), and spill or soilage alone (9%). The 8-year EFS and OS estimates for all patients with local stage III FHWT were 82% and 91%, respectively. Multivariate analysis demonstrated that both LN involvement (relative risk, 1.89; P = .005) and microscopic residual disease (relative risk, 1.87; P = .007) were predictive of EFS, and OS results were similar. There was no apparent difference in pattern of relapse according to stage III subtype. The rate of loss of heterozygosity was higher (6%) for those with positive LNs than for those without (2%; P = .05). CONCLUSION LN involvement and microscopic residual are the stage III criteria highly predictive of EFS and OS for patients with stage III FHWT. It is possible that in future studies, patients with different stage III criteria may receive different therapies.

Screening and Brief Intervention for Alcohol Problems in a University Student Health Clinic.

The purposes of this study were (1) to determine whether a university student health center (SHC) is a feasible location to introduce a campus-based screening and brief intervention (SBI) program for alcohol and (2) to determine whether the patients seen in the SHC differ in terms of the prevalence and severity of alcohol-related problems compared with students reported by emergency department programs. The authors used motivational interview techniques to counsel subjects from a convenience sample of patients waiting for medical treatment in the SHC who had screened positive with the Alcohol Use Disorders Identification Test (AUDIT). The authors interviewed patients again after 3 months. Seventy-five percent of eligible students participated. Sixty percent screened positive and received an intervention. The authors contacted 66 students (51.2%) again after 3 months. Seventy-five percent of students interviewed again after 3 months reported that SBI was helpful, 92% found the information clear, and 90% thought that the SHC was a good place to learn this information.

Nonmedical Prescription Opioid and Sedative Use Among Adolescents in the Emergency Department

OBJECTIVES: Nonmedical prescription opiate use (NPOU) and nonmedical prescription sedative use (NPSU) are serious public health concerns. The objectives of this study were to determine the prevalence and emergency department (ED) visit characteristics and other correlates associated with past-year NPOU and NPSU among adolescents and young adults using the ED. METHODS: Participants aged 14 to 20 presenting to the ED at the University of Michigan Medical Center between September 2010 and September 2011 were systematically recruited. A computerized self-report screening survey with validated items measuring past-year NPOU, NPSU, substance use, and violence was delivered to participants, and a retrospective chart review was performed. RESULTS: Of the 2135 participants (86.0% response rate), 222 (10.4%) reported either NPOU or NPSU. Among the 185 (8.7%) participants that reported NPOU, 14.6% had a current home prescription for an opioid and among the 115 (5.4%) with NPSU, 12.3% had a current home prescription for a sedative. After controlling for demographics (age, gender, race, public assistance), correlates of NPOU or NPSU included other substance use, and drinking and driving or riding with a drinking driver. Additional correlates of NPOU included receiving an intravenous opioid in the ED and for NPSU, dating violence, presenting to the ED for a noninjury complaint, and previous ED visit in the past year. CONCLUSIONS: Nearly 1 in 10 young people who use the ED for care report NPOU or NPSU, and only 12.3% and 14.6% report having current home prescriptions for sedatives and opioids. The ED represents a key location for screening and intervention efforts.

Canadian C-spine Rule and the National Emergency X-Radiography Utilization Low-Risk Criteria for C-spine radiography in young trauma patients

PURPOSE The Canadian C-spine (cervical spine) Rule (CCR) and the National Emergency X-Radiography Utilization Low-Risk Criteria (NLC) are criteria designed to guide C-spine radiography in trauma patients. It is unclear how these 2 rules compare with young children. METHODS This study retrospectively examined case-matched trauma patients 10 years or younger. Two cohorts were identified-cohort A where C-spine imaging was performed and cohort B where no imaging was conducted. The CCR and NLC criteria were then applied retrospectively to each cohort. RESULTS Cohort A contained 125 cases and cohort B with 250 cases. Seven patients (3%) had significant C-spine injuries. In cohort A, NLC criteria could be applied in 108 (86.4%) of 125 and CCR in 109 (87.2%) of 125. National Emergency X-Radiography Utilization Low-Risk Criteria suggested that 70 (58.3%) cases required C-spine imaging compared to 93 (76.2%) by CCR. National Emergency X-Radiography Utilization Low-Risk Criteria missed 3 C-spine injuries, and CCR missed one. In cohort B, NLC criteria could be applied in 132 (88%) of 150 and CCR in 131 (87.3%) of 150. The NLC criteria identified 8 cases and CCR identified 13 cases that would need C-spine radiographs. Fishers 2-sided Exact test demonstrated that CCR and NLC predictions were significantly different (P = .002) in both cohorts. The sensitivity of CCR was 86% and specificity was 94%, and the NLC had a sensitivity of 43% and a specificity of 96%. CONCLUSIONS Although CCR and NLC criteria may reduce the need for C-spine imaging in children 10 years and younger; they are not sensitive or specific enough to be used as currently designed.

Long-term functional outcome and quality of life in patients with high imperforate anus.

PURPOSE Anorectal malformations (ARMs) are associated with a large number of functional sequale that may affect a childs long-term quality of life (QOL). The purposes of this study were to better quantify patient functional stooling outcome and to identify how these outcomes related to the QOL in patients with high imperforate anus. METHODS Forty-eight patients from 2 childrens hospitals underwent scoring of stooling after 4 years of life. Scoring consisted of a 13-item questionnaire to assess long-term stooling habits (score range: 0-30, worst to best). These results were then correlated with a QOL survey as judged by a parent or guardian. RESULT Mean (SD) age at survey was 6.5 (1.6) years. Comparison of QOL and clinical scoring showed no signficant difference between the 2 institutions (P > .05). There was a direct correlation between the QOL and stooling score (Pearson r(2) = 0.827; beta coefficient = 24.7, P < .001). Interestingly, functional stooling scores worsened with increasing age (Pearson r(2) = 0.318, P = .02). Patients with associated congenital anomalies had a high rate of poor QOL (44% in poor range; P = .001). Stooling scores decreased significantly with increasing severity/complexity of the ARM (P = .001). CONCLUSION A large number of children experience functional stooling problems, and these were directly associated with poor QOL. In contrast to previous perceptions, our study showed that stooling patterns are perceived to worsen with age. This suggests that children with ARMs need long-term follow-up and counseling.