Abstracts of staff publications
aSpring 1998
Treatment of children and young adults with early-stage non-Hodgkin's lymphoma
Michael Link, Jonathan Shuster, Sarah Donaldson, Costan Berard, and Sharon Murphy
From the Department of Pediatrics and Radiation Oncology, Stanford University School of Medicine and the Lucile Salter Packard Children's Hospital, Stanford, Calif (ML, SD); the Department of Statistics, University of Florida, and the Pediatric Oncology Group Statistical Office, Gainesville, Fla. (JS); the Department of Pathology, Saint Jude Children's Research Hospital and the University of Tennessee, Memphis (CB); and the Department of Pediatrics, Northwestern University Medical School and Children's Memorial Hospital, Chicago (SM).
The New England Journal of Medicine 1997;337:1259–66
Background
: Children and young adults with early-stage non-Hodgkin's lymphoma have an excellent prognosis, but treatment is prolonged and is associated with many side effects. We performed two studies to determine whether therapy could be simplified.
Methods: Between 1983 and 1991, we conducted two consecutive trials in children and young adults (age, <21 years) with early-stage non-Hodgkin's lymphoma. In the first trial, patients were treated for 9 weeks with induction chemotherapy consisting of vincristine, doxorubicin, cyclophosphamide, and prednisone, followed by 24 weeks of continuation chemotherapy with mercaptopurine and methotrexate. Half the patients were randomly assigned to receive involved-field irradiation. In the second trial, after the 9 weeks of induction chemotherapy, the patients were randomly assigned to receive 24 weeks of continuation chemotherapy or no further therapy.
Results: A total of 340 patients were enrolled in the two trials, 12 of whom did not have complete remissions. One hundred thirteen patients received nine weeks of chemotherapy without radiotherapy, 131 received eight months of chemotherapy without radiotherapy, and 67 received eight months of chemotherapy with radiotherapy. At five years, the projected rates of continuous complete remission were 89, 86 and 88 percent for the three groups, respectively. At five years, event-free survival among the patients with early-stage lymphoblastic lymphoma was inferior to that among the patients with other subtypes of lymphoma (63 percent vs. 88 percent, P<0.001). Continuation therapy was effective only in patients with lymphoblastic lymphoma.
Conclusions: A nine-week chemotherapy regimen without irradiation of the primary sites of involvement is adequate therapy for most children and young adults with early-stage, nonlymphoblastic non-Hodgkin's lymphoma.
Differing birth weight among infants of U.S.-born blacks, African-born blacks, and U.S.-born whites
Richard David and James Collins
From the Division of Neonatology, Cook County Children's Hospital (RD); the Department of Pediatrics, School of Medicine, University of Illinois at Chicago (RD); the Divison of Neonatology, Children's Memorial Hospital (JC); and the Department of Pediatrics, Northwestern University Medical School, Chicago (JC).
The New England Journal of Medicine 1997;337;1209–14
Background: In the United States, the birth weights of infants of black women are lower than those of infants of white women. The extent to which the lower birth weights among blacks are related to social or genetic factors is unclear.
Methods: We used vital records for 1980 through 1995 from Illinois to determine the distribution of birth weights among infants of three groups of women — U.S.-born blacks, African-born blacks and U.S.-born whites.
Results: The mean birth weight of 44,046 infants of U.S.-born white women was 3446 g, that of 3135 infants of African-born black women was 3333 g, and that of 43,322 infants of U.S.-born black women was 3089 g. The incidence of low birth weight (weight less than 2500 g) was 13.2 percent among infants of U.S.-born black women and 7.1 percent among infants of African-born black women, as compared to 4.3 percent among infants of U.S.-born white women (relative risks, 3.1 and 1.6, respectively). Among the women at lowest risk (those 20 to 36 years old, with 12 years of education for themselves and their spouses, early prenatal care, gravida 2 or 3, and no previous fetal loss), the rate of low birth weight in infants of African-born black women (3.6 percent) was closer to the rate of infants of U.S.-born white women (2.4 percent), and the rate in infants of U.S.-born black women remained high (7.5 percent).
Conclusions: The birth-weight patterns of infants of African-born black women and U.S.-born white women are more closely related to one another than to the birth weights of infants of U.S.-born black women.
Otolaryngic manifestations in children presenting with apparent life-threatening events
J. Scott McMurray and Lauren D. Holinger
From the Department of Pediatric Otolaryngology and Maxillofacial Surgery (JM), Children's Hospital Medical Center, Cincinnati; and the Division of Pediatric Otolaryngology (LH), Children's Memorial Hospital, Chicago.
Otolaryngology—Head and Neck Surgery 1997;116:575–579
Apparent life-threatening event (ALTE) is a term used to characterize an event of unknown cause after an infant is found limp, cyanotic, bradycardic and/or requiring resuscitation.
Like sudden infant death syndrome (SIDS), ALTE is a general term used until a precise diagnosis can be established. The relationship between ALTE and SIDS has not been clearly defined, although 7 to 15 percent of children with ALTE die of SIDS. If children with ALTE are of greater risk for SIDS, morbidity and mortality may be prevented if the underlying pathology can be identified and corrected or closely monitored. The otolaryngologist is being consulted more frequently to evaluate children who have been through an ALTE to help elucidate any underlying pathology that may have caused the near-death experience. This retrospective chart review reports the evaluation of 30 infants with ALTE requiring consultation by the Division of Pediatric Otolaryngology at the Children's Memorial Hospital in Chicago during a 3-year period.
We reviewed the literature and here compare our findings with current animal models. Of the 30 children evaluated, 53% had gastroesophageal reflux, 40% had laryngeal abnormalities, 13% had treacheal abnormalities and 10% had pharyngeal abnormalities. Thirteen percent of the children had nonotolaryngic anomalies identified during evaluation. Surgical intervention was required in 10 patients and medical treatment was used in 18. When evaluating a child with ALTE, a complete history and physical examination, evaluation for gastroesophageal reflux, assessment for upper airway obstruction by radiographs and endoscopy and a multidisciplinary approach are recommended.
Tethered cord syndrome in low motor level children with myelomeningocele
John Sarwark, Daniel Weber, Ana Gabrieli, David McLone, and Luciano Dias
From Northwestern University Medical School and Children's Memorial Hospital, Chicago.
Pediatric Neurosurgery 1996;25:295–301
The clinical presentation of tethered spinal cord and the results of tethered cord release were examined in a group of 30 low motor level (L3 and below) children with a history of myelomeningocele without concomitant CNS complications.
Methods: Changes in orthopaedic and/or neurologic status formed the basis of consideration for tethered cord release. Clinically, these patients presented with a new onset or recently progressing scoliosis, spasticity with or without contractures, decrease in motor function and low back pain at the site of closure. One or more of these findings was present in all cases and led to the suspicion of tethered spinal cord. The diagnosis of tethered cord was confirmed in all cases by MRI or CT myeolography. In order to isolate tethering as the etiology for the patients' clinical deterioration, patients with concomitant CNS complications, e.g. shunt dysfunction or hydromyelia were excluded from the study. Twenty-nine such patients, of an initial 59, who would have otherwise been considered, were excluded on the basis of this criteria of concomitant CNS complications.
Results: The results of release 1 year after the procedure were as follows: regarding scoliosis, in 75% of cases the curve either remained stable or decreased by more than 10°, with 25% experiencing curve progression of >10°. The most recent follow-up in this group revealed that 11.8% experienced a decrease in curvature of >10°; 47.1% remained stable, and 41.2% ultimately progressed 10°. In the group with spasticity, 43.8% improved; 56.3% remained stable, and none worsened. Most (78.6%) of the children who had experienced a decline in motor function improved postoperatively, and all those with back pain experienced complete resolution.
Conclusion: Tethered cord release in symptomatic low lumbar and sacral level children with myelomeningocele appears to be of benefit, especially with respect to stabilization of scoliosis in selected patients, back pain at the site of closure, and prior decline in motor function. Results in the cases with spasticity were more equivocal.
Relation between intelligence and psychopathology among preschoolers
Karen Dietz, John Lavigne, Richard Arend, and Diane Rosenbaum
From Children's Memorial Hospital and Northwestern University Medical School, Chicago.
Journal of Clinical Child Psychology 1997;16(1):99–107
Background: Examined the relation between intelligence and psychopathology in a nonclinical sample of 510 children ages 2 to 5 years.
Method: Psychopathology was measured using both quantitative, dimensional methods (Child Behavior Checklist [CBCL]) and taxonomic methods (the Diagnostic and Statistical Manual of Mental Disorders [3rd. ed., Rev.; DSM-III-R; American Psychological Association, 1987]). IQ scores were derived from either the McCarthy Scales of Children's Abilities or the Bayley Scales of Mental Development.
Results: Based on quantitative, dimensional data, results support similar findings among older children and clinical populations that lower McCarthy general, verbal and perceptual-performance IQ scores are associated with various types of psychopathology. Results were also consistent for the DSM-III-R data. Bayley IQ scores did not predict CBCL psychopathology or DSM-III-R Disruptive Disorders, but they did predict the presence of a DSM-III-R diagnosis.
Conclusion: Early identification of intellectual deficits among preschoolers ages 3 to 5 may help prevent later school difficulties and severe psychopathology.
Twenty-four-hour pharmacokinetics of rectal acetaminophen in children: An old drug with new recommendations
Patrick Birmingham, Michael Tobin, Thomas Henthorn, Dennis Fisher, Maura Berkelham, Frederick Smith, Kaaren Fanta, and Charles Coté
From Children's Memorial Hospital and Northwestern University Medical School, Chicago; University of California, San Francisco; Washington University School of Medicine, St. Louis.
Anesthesiology 1997;87:244–252
Background: Rectal acetaminophen is often administered during operations to provide supplemental analgesia or antipyresis in children. Recent studies examining current dose guidelines are limited by short sampling times. The authors extended the drug sampling period to more clearly define acetaminophen pharmacokinetics in children having surgery.
Methods: Children (n=28) were randomized to receive a single dose of 10, 20, or 30 mg/kg rectal acetaminophen after induction of anesthesia. Venous blood samples were taken every 30 min for 4 h, every 60 min for 4 h, and every 4 h for 16 h. Data were analyzed using a mixed-effects modeling technique (using NONMEM software) to determine the volume of distribution and clearance normalized for bioavailability. Additional models accounted for suppository dissolution followed by acetaminophen absorption.
Results: Age, weight, estimated blood loss, volume of intravenous fluid administered, and anesthesia time were similar in the three groups. Most patients did not achieve peak or sustained serum values in the 10-20 µg/ml serum concentration range associated with antipyresis. The volume of distribution was 385 ml/kg, and clearance normalized for bioavailability, F, was 5.46 ml.
kg-1.
min-1. Pharmacokinetic models suggest that absorption of acetaminophen is a function of zero-order dissolution of suppositories and first-order absorption form the rectum. Suppository dose size also may affect absorption characteristics.
Conclusions: The current recommended rectal acetaminophen dose of 10–15 mg/kg yields peak serum concentrations less than the antipyretic serum concentration of 10–20 µg/ml. Based on the observed kinetics, the authors recommend that the initial dose should be approximately 40 mg/kg.
Social factors predicting postpartum choice of norplant among African-American and non-Hispanic white adolescents
Cynthia Mears, Mary Hediger, Steven Martin, Theresa Scholl, and Janet Kramer
From the Department of Pediatrics, Division of Adolescent Medicine, Medical Center of Delaware, Newark, Delaware; the Department of Obstetrics & Gynecology, University of Medicine and Dentistry of New Jersey, School of Osteopathic Medicine, Stratford, New Jersey; and the University of Delaware, Newark, Delaware. (Dr. Mears is now at Children's Memorial Hospital in Chicago.)
Journal of Adolescent Health 1997;21:167–171
Background: This study was designed to determine the factors associated with Norplant choice for postpartum teens.
Methods: A total of 151 teenagers, ages 12–20 years, who delivered at the Medical Center of Delaware from July to December 1992, were offered insertion of Norplant within 48 h postpartum. A structured interview was conducted in the postpartum period after nondirective counseling sessions, including a physical demonstration using anatomical model of various contraceptive methods. Student's t-tests, chi-square, and multivariate analysis were used.
Results: Eighty-six teenagers were African-American (mean age = 17.3 ± 1.9 years) and 65 non-Hispanic white (NHW) (mean age 18.3 ± 1.5 years). The NHW teenagers were older (p < 0.001); the African-American teenagers were more likely to have Medicaid (49% vs. 14%; p < 0.001) and to have one or more friends who use Norplant (62% vs. 34%; p < 0.001). In multivariate analyses, NHW teenagers were more likely to choose Norplant if they had discussed their choice with a parent or guardian (adjusted odds ratio (AOR) = 14.6, 95% confidence interval (CI), 2.12-100.57); had Medicaid funding (AOR = 12.1; 95% (CI), 10.6-91.34); and had any friends who used Norplant (AOR = 6.3; 95% (CI), 1.38-28.40). However, for African-American teenagers, the strongest predictor for choice of Norplant was number of prior children delivered. After two deliveries, there was a better than four-fold likelihood (AOR = 4.8; 95% (CI), 1.47-15,94) that African-American teenagers would choose Norplant. For the African-American teenagers, parental discussion, Medicaid status, and friends' use of Norplant were not as important as family size, but far greater percentages of the African-American teenagers had access to Medicaid funding and peers who used Norplant.
Conclusions: NHW and African-American teenagers choose Norplant for different reasons. Lack of funding may have been a barrier to choosing Norplant. Discussions with parents and friends have a positive influence on choosing Norplant for NHW teenagers. African-American teenagers were more likely than NHW to have Medicaid coverage, and more frequently choose Norplant if the current birth was their third child.
Strategies for managing group A streptococcal pharyngitis: A survey of board-certified pediatricians
Catherine Hofer, Helen Binns, and Robert Tanz
From the Department of Pediatrics, Division of General Academic Pediatrics, Children's Memorial Hospital, Northwestern University Medical School, Chicago. (Dr. Hofer is now with the Central Plains Clinic, Sioux Falls, SD.)
The Archives of Pediatric Adolescent Medicine 1997;151:824–829
Objectives: To assess the management strategies and knowledge of board-certified pediatricians regarding group A ß-hemolytic streptococcal (GABHS) pharyngitis.
Design: Survey of 1000 US pediatricians in 1991, chosen randomly from the membership of the American Academy of Pediatrics. The survey included questions related to 2 clinical scenarios, respondent demographics, and knowledge of streptococcal pharyngitis.
Subjects: Pediatricians who treated patients with pharyngitis. Of the 690 surveys that were returned, 510 pediatricians treated patients with pharyngitis and were included in the data analysis.
Data Analysis: Data were analyzed using x2 statistics for categorical data and the Student t test for continuous variables.
Results: Antigen detection tests (ADTs) were used by 64% of the pediatricians; 85% used throat cultures. Strategies for diagnosing streptococcal pharyngitis were throat cultures alone (38%), consider positive ADTs definitive and use throat culture when ADTs are negative (42%), ADT alone (13%), ADT and throat culture for all patients with pharyngitis (5%), and no tests for GABHS performed (2%). Thirty-one percent usually or always treated with antibiotics before test results were available. Only 29% of these "early treaters" always discontinued antibiotics when tests did not confirm the presence of group A streptococci. The drug of choice for treatment was penicillin (73%); another 26% preferred a derivative of penicillin, particularly amoxicillin. Many pediatricians altered their management when a patient had recurrent streptococcal pharyngitis. Nearly half of the respondents would use a different antibiotic than they used for routine acute streptococcal pharyngitis. They most often changed to erythromycin (25%), cefadroxil (23%), or amoxicillin-clavulanate (20%). Follow-up throat culture was obtained by 51% of pediatricians after treatment of recurrent streptococcal pharyngitis. A patient with chronic carriage of GABHS and symptoms of pharyngitis would be treated with an antibiotic by 84%; most (62%) would use a penicillin. Other choices were cephalosporins (19%), erythromycin (12%), clindamycin (3%), or rifampin plus penicillin (3%). Tonsillectomy was recommended for symptomatic carriers by 31% of respondents. Carriers without symptoms were less likely to be treated with antibiotics (23%) or referred for tonsillectomy (21%).
Conclusions: Most surveyed board-certified pediatricians managed acute GABHS pharyngitis appropriately, but 15% to 20% used diagnostic or treatment strategies that are not recommended. There was lack of a consensus about the management of recurrent GABHS pharyngitis and chronic carriage of GABHS.
