bluuebunny/crossref_metadata_2025 huggingface dataset:
A Rare Presentation of Childhood Pompe Disease: Cardiac Involvement Provoked by Epstein-Barr Virus Infection
Authors: Talsma Melle D. , Kroos Marian A. , Visser Gepke , Kimpen Jan L.L. , Niezen Klary E.
Published: August 2004

Myocarditis attributed to Epstein-Barr virus (EBV) as the sole cause is a rare manifestation. Myocarditis ascribed to EBV infection in combination with other factors has been reported in a few more cases. We report a child who experienced active EBV infection and later, at 19 months of age, received a diagnosis of Pompe disease (acid α-glucosidase deficiency) with predominant cardiac involvement. The cardiac symptoms resolved at the end of the EBV infection. When the patient was recently seen, at 8 years of age, she had an increased left ventricular wall thickness but normal cardiac function. DNA analysis identified this patient as compound heterozygote for a mutant Tyr292Cys and a null allele. In light of genotype-phenotype correlation, it is notable that a Spanish patient with a functionally similar genotype (Tyr292Cys/Arg854Stop) also had childhood Pompe disease with peripheral muscular involvement.
Rising Prevalence of Antidepressants Among US Youths
Authors: Zito Julie Magno , Safer Daniel J. , dosReis Susan , Gardner James F. , Soeken Karen , Boles Myde , Lynch Frances
Published: August 2004

Objective. To examine changes in antidepressant (ATD) prevalence and the sociodemographic and clinical correlates of ATD use among youths who are treated in community practice settings.

Methods. A retrospective study was undertaken using large data sets from 3 US sites. Outpatient prescription and clinical service records of youths who were aged 2 to 19 and enrolled in Midwestern Medicaid (MWM) and mid-Atlantic Medicaid (MAM) state programs and a group-model health maintenance organization (HMO) were organized into seven 1-year cross-sectional data sets from 1988 through 1994 to evaluate ATD utilization patterns.

Results. In 1994, ATD prevalence per 1000 youths was 19.10 (MWM), 17.78 (MAM), and 12.85 (HMO), which represented a consistent increase in prevalence from 1988–1994: 2.9-fold (MWM), 4.6-fold (MAM), and 3.6-fold (HMO). Despite the rapidly expanding use of selective serotonin reuptake inhibitors prescribed mainly for depression, more than half of ATD use in 1994 was still attributable to tricyclic antidepressants prescribed mainly for attention-deficit/hyperactivity disorder. ATD prevalence was generally predominant among 10- to 14-year-old boys and among 15- to 19-year-old girls. In the Medicaid populations, 42% (MAM) and 72% (MWM) of ATD-treated youths had primary care services, whereas the bulk of the remainder had psychiatric services. Attention-deficit/hyperactivity disorder followed by depression led the physician-reported primary care diagnoses associated with ATD use, whereas that diagnostic rank order was reversed for youths who received psychiatric services.

Conclusions. ATD treatments among youths substantially increased in the 1990s. This was generated primarily by primary care providers, and thus evaluations of the outcome of ATD treatment need to target primary care in addition to psychiatric providers. Longitudinal study designs are needed to evaluate the use of ATDs in youths in regard to the duration of treatment, combination medications, and the reasons for treatment.
Factors Associated With Prescription Drug Expenditures Among Children: An Analysis of the Medical Expenditure Panel Survey
Authors: Chen Alex Y. , Chang Ruey-Kang R.
Published: August 2004

Objective.Pharmaceutical costs have reached 14% of total health care costs in the United States and continue to rise. Many studies have looked at factors that influence utilization of hospital and ambulatory care services in the pediatric population. This study examines the factors that influence utilization of prescription drugs in the pediatric population.

Methods.Data from the 1996 Medical Expenditure Panel Survey (MEPS) were used in the analysis. A 2-part multivariate regression analysis was conducted using pediatric (ages 0–17) prescription drug expenditures as the dependent variable. Independent variables were constructed using demographic variables, socioeconomic variables, health status, and medical conditions.

Results.Black children are less likely than white children to use any prescription drug (odds ratio: 0.67). Similarly, uninsured children are less likely than privately insured children to use any prescription drug (odds ratio: 0.62). Among children who had any prescription drug expenditure in 1996, children who are black, Asian, and Hispanic had lower prescription drug expenditures than children who are white. Children who are uninsured had lower expenditures than children who are privately insured. Children in near-poor families had lower prescription drug expenditures than those in high-income families, even after controlling for insurance status. Children who are covered by Medicaid had comparable prescription drug expenditures to children who are covered by private insurance.

Conclusion.Socioeconomic characteristics such as race, insurance status, and family income levels had significant impact on pediatric prescription drug expenditures, even after controlling for the influences of health status and medical conditions.
Parent and Physician Attitudes Regarding Electronic Communication in Pediatric Practices
Authors: Kleiner Katie D. , Akers Rachel , Burke Bonnie L. , Werner Eric J.
Published: August 2004

Objective. To determine 1) the electronic mail (e-mail) capabilities of families, general pediatricians (GPs), and subspecialty pediatricians (SPs) from an integrated pediatric health care delivery system and 2) the knowledge base and attitudes of these groups regarding the potential issues involved in using e-mail for physician-patient communication.

Methods. Parents were interviewed in the offices of participating practices using a standardized survey tool. Pediatricians and staff were interviewed using a separate instrument. The data were entered into a database for analysis.

Results. A total of 325 parents and 37 physicians were interviewed. Fifty-seven percent of the 161 parents who were interviewed at the GP offices and 66% of the 164 families that were interviewed at SP offices had access to e-mail. Parents aged 31 to 40 years were significantly more likely to have access to e-mail than parents of other age groups. Access to e-mail increased with family income and parental education. Most (74%) parents who were interviewed expressed interest in using e-mail to contact their child’s physician/physician’s office for several purposes, including getting information or test results, scheduling appointments, and/or discussing a particular symptom. Although both groups of parents expressed concerns about confidentiality, parents at the GP offices were significantly more concerned (medianGP = 95 vs medianSP = 70). Seventy-four percent of GPs and 100% of SPs had access to e-mail; however, 79% did not want to use e-mail for physician-patient communication, citing concerns about confidentiality and the time demands that patient e-mail might engender.

Conclusions. The majority of parents and pediatricians at both general and subspecialty pediatric offices are capable of communicating electronically. Parents and pediatricians are aware of the issues surrounding e-mail use for patient communication. Most parents express an interest in using e-mail for patient-physician communications, whereas most physicians are opposed to this practice.
Performance Profiles: The Influence of Patient Satisfaction Data on Physicians’ Practice
Authors: Rider Elizabeth A. , Perrin James M.
Published: August 2004

Objective. Health maintenance organizations and other payers increasingly use patient satisfaction data to profile physician performance. Little is known about physicians’ use of patient satisfaction information or how profiles affect individual physician behaviors. The objective of this study was to examine primary care physicians’ perceptions of performance profiles based on patient satisfaction data, whether physicians use profiles to change practice behaviors, and which profile components physicians think are important for assessing quality of care.

Methods. A written survey was conducted in 1998 in Massachusetts with 810 primary care physicians (304 pediatricians, 201 family practitioners, 305 internists) who had at least 100 patients in a large managed care plan and had received 1 or more profiles based on patient satisfaction data. Physicians in training were excluded. Physicians’ perceptions of profiles and their reported use to change practice behaviors were measured.

Results. The response rate was 68%. Twenty-three percent reported that profiles were very or extremely useful for improving care. Only 7% reported using profiles often or always to change care. Although specific profile components related to interpersonal aspects of care were rated more useful, <11% reported using profiles often or always to make changes on any individual component. A majority, 67% to 89%, reported making no or minor changes on profile components. Responses did not vary by specialty, demographics, or practice characteristics. Physicians rated interpersonal factors (eg, ability to communicate with patients, ability to show caring and empathy) as the most important indicators of quality of care; they report having the most control over these factors. Office factors (eg, staying on schedule, ease of scheduling appointments) were ranked as least important for assessing quality of care.

Conclusion. Although health maintenance organizations and other payers increasingly use patient satisfaction reports to profile individual physicians and guide physician compensation and health plan participation, <25% of primary care physicians find profiles useful for improving patient care and even fewer report using profiles to change practice. Profiles likely have limited influence on behavior changes. Payers who invest in profiles may find it advantageous to focus on health plans and practice facilities rather than on individual physicians.
Ventilator-Associated Pneumonia in Pediatric Intensive Care Unit Patients: Risk Factors and Outcomes
Authors: Elward Alexis M. , Warren David K. , Fraser Victoria J.
Published: August 2004

Objectives. To determine the rates, risk factors, and outcomes of ventilator-associated pneumonia in pediatric intensive care unit (PICU) patients.

Methods. A prospective cohort study was conducted at the St Louis Children’s Hospital PICU on all patients who were admitted to the PICU from September 1, 1999, to May 31, 2000, except those who died within 24 hours, were ≥18 years of age, or were neonatal intensive care unit patients on extracorporeal membrane oxygenation. The primary outcome measured was the development of ventilator-associated pneumonia. Secondary outcomes were death and hospital and PICU length of stay. Multiple logistic regression analysis was performed to determine independent predictors for ventilator-associated pneumonia.

Results. There were 34 episodes of ventilator-associated pneumonia in 30 patients of 911 admissions (3.3%) and 595 (5.1%) mechanically ventilated patients. The mean ventilator-associated pneumonia rate was 11.6/1000 ventilator days. By logistic regression analysis, genetic syndrome (odds ratio [OR]: 2.37; 95% confidence interval [CI]: 1.01–5.46), reintubation (OR: 2.71; 95% CI: 1.18–6.21), and transport out of the PICU (OR: 8.90; 95% CI: 3.82–20.74) independently predicted ventilator-associated pneumonia.

Conclusions. Ventilator-associated pneumonia occurs at significant rates among mechanically ventilated PICU patients and is associated with processes of care. Additional studies are necessary to develop interventions to prevent ventilator-associated pneumonia.
Evaluation of Young Children in Contact With Adult Multidrug-Resistant Pulmonary Tuberculosis: A 30-Month Follow-up
Authors: Schaaf H. Simon , Gie Robert P. , Kennedy Magdalene , Beyers Nulda , Hesseling Peter B. , Donald Peter R.
Published: August 2004

Setting. The Western Cape Province of South Africa, an area with a high tuberculosis (TB) incidence, where initial multidrug resistance (MDR) among adult TB cases was 1.1% during 1992–1993.

Objective. To determine the long-term prevalence of TB infection and disease in children in household contact with adults with MDR pulmonary TB, and to establish the efficacy of chemoprophylaxis in preventing disease in these children.

Method. Children <5 years old in contact with 73 MDR TB adults were evaluated. Disease was treated by prescribing at least 2 drugs to which the adult’s strain was susceptible. The remaining children were classified as infected or noninfected and received chemoprophylaxis according to the index’s strain susceptibility or were followed up and treated when indicated. All were followed up for 30 months.

Results. At the initial evaluation 125 children were seen, median age 27.5 months. Of these, 119 were followed up. Fourteen (12%) had disease, 61 (51%) were infected only, and 44 (37%) were noninfected. By 30-month follow-up, 29 (24%) had developed disease and 64 (54%) were infected only. Four adult-child pair Mycobacterium tuberculosis isolates were compared by DNA fingerprinting; 3 were identical. All children who developed TB disease were clinically cured. Two (5%) of 41 children who received appropriate chemoprophylaxis and 13 (20%) of 64 who did not, developed TB during follow-up (odds ratio: 4.97).

Conclusion. The study confirms MDR TB transmission to childhood contacts. Seventy-eight percent of children were infected or developed disease. Appropriate chemoprophylaxis may prevent disease in these children.
Comparison Between Simultaneously Recorded Amplitude Integrated Electroencephalogram (Cerebral Function Monitor) and Standard Electroencephalogram in Neonates
Authors: Toet Mona C. , van der Meij Wil , de Vries Linda S. , Uiterwaal Cuno S. P. M. , van Huffelen Kees C.
Published: August 2004

Objective: To assess the value and the limitations of amplitude integrated electroencephalogram (EEG) using the cerebral function monitor (CFM) in comparison with standard EEG in neonates who have hypoxic ischemic encephalopathy or were suspected of having convulsions.

Methods. In 36 neonates with a gestational age ≥36 weeks, CFM and simultaneously recorded EEG traces were analyzed off-line and independently classified. CFM background activity: continuous normal voltage; continuous normal voltage, slightly discontinuous (DNV); burst-suppression (BS); continuous extremely low voltage; flat tracing. CFM epileptiform activity: suspected epileptic activity, single seizure (SS), repetitive seizures (RS), status epilepticus (SE). EEG background activity: normal, depressed, low voltage undifferentiated, excessive discontinuity, BS, no activity. Epileptiform activity: interictal unifocal, interictal multifocal, ictal unifocal, ictal multifocal, SE.

Results. A total of 33 traces were suitable for analysis. Interobserver agreement on background activity was reached in 31 cases (κ = 0.92) for CFM and in 27 cases (κ = 0.74) for EEG. There was full agreement on CFM ictal activity (RS, SS, or SE) and EEG ictal activity. A normal CFM (continuous normal voltage) corresponded with a normal or a depressed EEG in 90% of the cases. The positive predictive value for a severely abnormal CFM (BS, continuous extremely low voltage, flat tracing) to correspond with a severely abnormal EEG (excessive discontinuity, BS, low voltage undifferentiated, no activity) was 100% (negative predictive value, 80%; sensitivity, 76%; specificity, 100%). DNV (10) on CFM corresponded either with depressed (6) or excessive discontinuity (4) on EEG. Ictal activity on EEG corresponded with SS, RS, or SE on CFM in 8 cases (sensitivity, 80%; specificity, 100%; positive predictive value, 100%; negative predictive value, 92%).

Conclusion. CFM is a reliable tool for monitoring both background patterns (especially normal and severely abnormal) and ictal activity. Certain focal, low amplitude, and very short periods of seizure discharges can be missed. We recommend using CFM as a monitoring device and performing intermittent standard EEG whenever there is any doubt about the classification of the CFM (ie, DNV pattern or suspected epileptiform activity).
Efficacy of the Ketogenic Diet for Infantile Spasms
Authors: Kossoff Eric H. , Pyzik Paula L. , McGrogan Jane R. , Vining Eileen P. G. , Freeman John M.
Published: August 2004

Objective. The objective of this study was to determine whether the ketogenic diet is safe, well-tolerated, and efficacious in the treatment of infantile spasms.

Methods. During a 4-year period, 23 children with infantile spasms, aged 5 months to 2 years, were started on the ketogenic diet; 9 (39%) had symptomatic infantile spasms, and 16 (70%) had hypsarrhythmia. Children had an average prediet exposure to 3.3 anticonvulsants. Two children were enrolled before any medication had been tried. Seizure reduction was analyzed retrospectively, using parent reports and electroencephalograms (EEGs) when available.

Results. At 3, 6, 9, and 12 months, 38%, 39%, 53%, and 46%, respectively, of all patients currently on the diet were >90% improved (3 were seizure-free at 12 months); 67%, 72%, 93%, and 100% were >50% improved. Fifty-six percent remained on the diet at 12 months, 46% of whom were >90% improved and 100% were >50%. Fifty percent of those with hypsarrhythmia and follow-up EEGs had EEG improvement. Fifty-seven percent had their medications reduced or discontinued by 12 months. Fifty-seven percent had improvement in development, which was correlated with seizure control. Independent factors that predicted improvement included age younger than 1 year and previous exposure to 3 or fewer anticonvulsants. No child has died, and 7 children had diet-related adverse reactions (nephrolithiasis, gastroesophageal reflux).

Discussion. The ketogenic diet is a safe, well-tolerated, and possibly effective potential alternative to other therapies for infantile spasms.
Caffeine Impairs Cerebral and Intestinal Blood Flow Velocity in Preterm Infants
Authors: Hoecker Christina , Nelle Mathias , Poeschl Johannes , Beedgen Bernd , Linderkamp Otwin
Published: August 2004

Objective. In adults, a single dose of 250 mg of caffeine may decrease cerebral blood flow by 30%. In preterm infants, caffeine is commonly used for the treatment and prophylaxis of apnea. The purpose of this investigation was to assess effects of caffeine on circulatory parameters in preterm infants.

Methods. We studied 16 preterm neonates with a mean gestational age (mean ± standard deviation) of 31 ± 1.2 weeks (range: 29–33 weeks), birth weight of 1400 ± 380 g (range: 625-2060 g), and postnatal age of 24 to 72 hours before and 1 and 2 hours after an oral loading dose of 25 mg/kg pure caffeine. We investigated left ventricular output (LVO), cerebral blood flow velocity (BFV) of the internal carotid artery (ICA) and the anterior cerebral artery, and intestinal BFV of the celiac artery and superior mesenteric artery by Doppler sonography.

Results. Mean BFV in the ICA decreased significantly 1 (17%) and 2 hours (22%) after caffeine administration. Mean BFV in the anterior cerebral artery showed a reduction of 14% after 2 hours. The mean BFV in the superior mesenteric artery decreased significantly 1 and 2 hours after caffeine administration (30%). Mean BFV in the celiac artery showed a significant reduction of 14% 1 hour after caffeine. No changes were observed in LVO, blood pressure, and heart rate.

Conclusion. Oral administration of a high loading dose of caffeine results in marked reduction of cerebral and intestinal BFV, without changing LVO, blood pressure, and heart rate.
Demography of Pediatric Primary Care in Europe: Delivery of Care and Training
Authors: Katz Manuel , Rubino Armido , Collier Jacqueline , Rosen Joel , Ehrich Jochen H. H.
Published: August 2004

Objective. The Union of National European Pediatric Societies and Associations recognized the lack of information regarding demography of delivery of care and training for the doctors who care for children in Europe. Therefore, the Union of National European Pediatric Societies and Associations studied factors and explanations for the variation between countries regarding pediatric primary care (PPC) and community pediatrics (CP) as well as the extent of formal training provided for those who take care of children at the community level.

Methods. An explanatory letter and a questionnaire with 12 questions regarding delivery of PPC and CP and training was mailed to the president of each of 41 national pediatric societies in Europe. Statistical data about population, country’s income, and infant mortality rate (IMR) were also obtained from World Health Organization data. Statistical analysis using multivariate and linear regression was conducted to ascertain which variables were associated with IMR. Descriptive statistics regarding demography and training are also reported.

Results. In 1999, a total of 167 444 pediatricians served a population of 158 million children who were younger than 15 years and living in the 34 reporting European countries. The median number of children per pediatrician was 2094; this varied from 401 to 15 150. A pediatric system for PPC existed in 12 countries; 6 countries had a general practitioner system, and a combined system was reported from 16 countries. Pediatricians did not work at the primary care level at all in 3 countries. In 14 of 34 countries, pediatricians worked in various aspects of community medicine, such as developmental pediatrics, well-infant care, school physicians, and so forth. IMR was lower in countries with a higher income per capita. In addition, a pediatric system of primary care had a protective effect when looking at IMR as the outcome. In 75% of the countries, some form of training in pediatric care for pediatricians was reported; the corresponding data for general practitioners was 60%. Community-based teaching programs were offered to pediatricians and general practitioners in a minority of countries only.

Conclusions. At the end of the century, Europe showed a considerable variation in both delivery of PPC and training for doctors who care for children. This study identified 3 different health care delivery systems for PPC, as well as 2 types of pediatricians who work in community-based settings. Formal training in PPC or CP for both pediatricians and general practitioners varied from established curricula to no teaching at all. Economic and sociopolitical issues, professional power, and geographical and historical factors may explain the differences in pediatric care among European countries.
Association Between Infantile Colic and Carbohydrate Malabsorption From Fruit Juices in Infancy
Authors: Duro Debora , Rising Russell , Cedillo Maribel , Lifshitz Fima
Published: August 2004

Objective. To determine whether infantile colic (IC) is associated with malabsorption of carbohydrates present in fruit juices.

Methods. In this double-blind study, parents of 30 healthy infants (5.1 ± 0.7 months, 7.4 ± 1.0 kg, 64 ± 4 cm) were administered a questionnaire to quantitatively assess IC. Thereafter, they were divided into 2 groups, 16 infants with and 14 without IC. Within each treatment group infants were fed 120 mL (16.3 ± 2.0 mL/kg) of either white grape (sorbitol-free; 1:1 fructose-to-glucose ratio) or apple (sorbitol 0.5 g/dL; 2.6:1 fructose-to-glucose ratio) juice. Physical activity (PA), energy expenditure (EE), crying, and sleeping times were measured for 0.5 and 3.0 hours before and after juice feeding, respectively, using the Enhanced Metabolic Testing Activity Chamber. Carbohydrate malabsorption was determined by breath hydrogen (BH2) gas analysis after juice feedings. Statistical differences between groups were determined by 2-way analysis of variance with the Tukey procedure.

Results. Infants with IC fed apple juice exhibited carbohydrate malabsorption as shown by increased BH2 excretion, whereas those without IC absorbed carbohydrates normally when fed this juice. Infants fed apple juice with carbohydrate malabsorption cried more and consequently slept less during the last 1.5 hours of the study. This was associated with increased PA and EE as compared with infants without IC fed apple juice. In contrast, infants fed white grape juice, regardless of IC, showed no increase in BH2 excretion, PA, and EE. Furthermore, crying and sleeping times were unchanged in infants fed white grape juice regardless of the presence or absence of IC.

Conclusions. IC was associated with carbohydrate malabsorption from fruit juices containing sorbitol and a high fructose-to-glucose ratio.
Assent Observed: Children’s Involvement in Leukemia Treatment and Research Discussions
Authors: Olechnowicz Joseph Quinn , Eder Michelle , Simon Christian , Zyzanski Stephen , Kodish Eric
Published: August 2004

Objective. Assent is a critical issue in pediatric ethics that has not been well-studied. We examined the role of older children in discussing a recent diagnosis of acute leukemia and treatment options, including participation in a randomized, clinical trial (RCT).

Design. Our sample was drawn from data collected as part of a larger, National Cancer Institute-funded study in which we observed, tape-recorded, and transcribed the informed consent conference (ICC) for children with leukemia at 6 institutions. We analyzed the data for the child’s presence and role, examined 5 discussion categories relevant to assent in the context of pediatric cancer treatment/research, conducted parent interviews, and administered clinician questionnaires to examine these issues. We report a qualitative analysis of 14 cases in which the child was present for the ICC.

Results. Clinicians varied with regard to whom they directed specific discussions when patients were present. Questions asked by the children predominantly related to details of the disease and treatment, with few questions about the RCT. Clinicians and parents attribute responsibility for decision-making about participation in RCTs in a variety of ways. In conferences that included the child-patient, parents asked significantly fewer questions than in other ICCs.

Conclusion. There is significant variation among ICCs that include the older child. Additional empirical study of assent is warranted, and our data suggest several hypotheses that should be tested in future research.
Validity of Maternal Report of Prenatal Alcohol, Cocaine, and Smoking in Relation to Neurobehavioral Outcome
Authors: Jacobson Sandra W. , Chiodo Lisa M. , Sokol Robert J. , Jacobson Joseph L.
Published: August 2004

Objective. Evidence that mothers report higher levels of drinking retrospectively than during pregnancy has led some investigators to suggest that women systematically underreport alcohol antenatally and that alcohol-related deficits may actually reflect heavier prenatal exposure. This study is the first to compare the validity of antenatal and retrospective reports of pregnancy drinking, drug use, and smoking in relation to effects on infant neurobehavioral outcomes.

Methodology. Three hundred fifty-four inner-city mothers were interviewed regarding their alcohol, drug use, and smoking during pregnancy and retrospectively at 13 months’ postpartum. Their infants were assessed at 6.5, 12, and 13 months on a large battery of neurobehavioral assessments.

Results. Although higher levels of alcohol were reported retrospectively, the correlations of prenatal alcohol exposure with infant outcome were as strong or stronger for the antenatal measures and only the antenatal reports predicted poorer cognitive performance on the Bayley Scales and symbolic play, slower processing speed on the Fagan Test of Infant Intelligence and cross-modal transfer, and slower infant reaction time. Women also reported higher levels of cocaine and marijuana but not cigarette smoking retrospectively. Relations between cocaine use and smoking on birth size and gestational age were as strong for either report. No effects were detected in relation to either report of marijuana use during pregnancy.

Conclusions. These findings suggest that antenatal alcohol interviews provide the most valid information and demonstrate the importance of assessing prenatal alcohol use during pregnancy to minimize the risk of failing to detect neurobehavioral deficits. Adverse effects were consistently seen at levels as low as 0.5 oz absolute alcohol/day (the equivalent of 7 drinks per week) based on maternal antenatal report. These data suggest that alcohol-related deficits do not reflect heavier prenatal exposure than that reported during pregnancy and that threshold values derived from antenatal reports are reasonably accurate.
Viral Respiratory Infection in Schoolchildren: Effects on Middle Ear Pressure
Authors: Winther Birgit , Hayden Frederick G. , Arruda Eurico , Dutkowski Regina , Ward Penelope , Hendley J. Owen
Published: August 2004

Objective. To evaluate the effect of uncomplicated viral respiratory infections (colds) on middle ear pressure in healthy school-aged children.

Methods. Children (ages 2–12) with normal tympanograms before onset of illness had bilateral tympanometry daily except weekends for 2 weeks after the onset of a cold. Nasopharyngeal secretion obtained at onset of illness was cultured for bacterial pathogens of otitis media using selective agars and tested for rhinovirus, coronavirus, respiratory syncytial virus, influenza A and B, and parainfluenza 1–3 by reverse transcriptase polymerase chain reaction technology. Tympanometry was designated as abnormal with peak pressure of ≤−100 daPa or ≥50 daPa and/or a compliance peak of <0.2 cm3.

Results. Eighty-six colds were studied, 82 in schoolchildren (5–12 years old) and 4 in 2- to 3-year-olds. Abnormal negative middle ear pressure occurred at least once during the 2 weeks after onset in 57 (66%) of the 86 colds. Tympanometry was abnormal in the first week after onset in 50 (88%) of the 57 colds and was abnormal on a single day in 17 (30%) of the 57. The middle ear pressure abnormalities were intermittent and shifted from one ear to the other ear from day to day. Reverse transcriptase polymerase chain reaction was positive for a respiratory virus in 56 (65%) of the 86 illnesses. Rhinovirus was found in 48% and respiratory syncytial virus in 14%. Pathogenic bacteria (Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis) were detected in nasopharyngeal secretion in 29 (34%) of the 86 colds; the bacteria were in high titer (≥103 cfu/mL) in 26 of the 29 positive specimens. None developed illness that required a visit to a physician.

Age, detection of a respiratory virus, and presence of bacterial pathogen in the nasopharyngeal secretion had a negligible effect on the occurrence of abnormal tympanometry. Occurrence of negative middle ear pressure in winter-spring colds was significantly greater than in fall colds for unexplained reasons.

Conclusions. Transient negative middle ear pressure occurred in two thirds of uncomplicated colds in healthy children. This negative pressure, which may facilitate secondary viral or bacterial otitis media, seems to result from viral infection of the nasopharynx and distal tube causing bilateral eustachian tube dysfunction. Tympanometry provides an objective measure of the potential beneficial effects of investigational treatments on the risk of eustachian tube dysfunction/otitis media.
Occurrence of Celiac Disease After Onset of Type 1 Diabetes: A 6-Year Prospective Longitudinal Study
Authors: Barera Graziano , Bonfanti Riccardo , Viscardi Matteo , Bazzigaluppi Elena , Calori Giliola , Meschi Franco , Bianchi Cesare , Chiumello Giuseppe
Published: August 2004

Objective. To investigate the prevalence of celiac disease in a large cohort of children and adolescents at the onset of type 1 diabetes and the occurrence of new cases during a 6-year follow-up.

Methods. We prospectively studied, by repeated serologic screening, 274 consecutive patients at the onset of type 1 diabetes (age [mean ± standard deviation]: 8.28 ± 4.65 years) for 6 subsequent years. One patient had a diagnosis of celiac disease before the onset of diabetes. The immunoglobulin A-antiendomysium antibody test was selected as the screening test; patients with positive results (++ or +++) or with 2 consecutive weak positive tests (+) were considered appropriate for the jejunal biopsy.

Results. At diabetes onset, 15 (5.5%) of 273 patients tested positive with the antiendomysium test; jejunal biopsy was performed in 10, and celiac disease was diagnosed in 9. The prevalence of biopsy-confirmed celiac disease at the manifestation of diabetes was 3.6% (10 of 274 patients). Twelve more patients with a negative antiendomysium antibody test at diabetes onset tested positive during the follow-up within 4 years; 10 of them had biopsies performed, and 7 had celiac disease. Therefore, the overall prevalence of biopsy-confirmed celiac disease in the entire cohort of patients was 6.2%. The age at diabetes onset in patients with and without celiac disease was not different (7.88 ± 5.69 vs 8.3 ± 4.58 years). The majority of cases of celiac disease were asymptomatic in their presentation, and no signs of overt malnutrition were documented.

Conclusions. The prevalence of celiac disease in patients with type 1 diabetes is approximately 20 times higher than in the general population. Sixty percent of cases are already present at diabetes onset, mostly undetected, but an additional 40% of patients develop celiac disease a few years after diabetes onset. Extending screening programs for celiac disease after the onset of type 1 diabetes is recommended, even in the absence of clinical symptoms.
Hepatitis A Virus Infections in the United States: Model-Based Estimates and Implications for Childhood Immunization
Authors: Armstrong Gregory L. , Bell Beth P.
Published: August 2004

Objective. The high prevalence of antibody to hepatitis A virus (HAV) in the US population suggests that the incidence of infection is much higher than reported, but the infection rate is difficult to measure directly because of anicteric infection and underreporting. We present a model that reconciles the reported incidence of hepatitis A with the observed prevalence of antibody to HAV and provides an estimate of the true incidence of HAV infection.

Methods. In the model, reported incidence of hepatitis A in the United States was adjusted to account first for anicteric infection and then for underreporting and declining incidence over time such that the prevalence predicted by the model approximated that observed in 2 nationwide surveys.

Results. The model showed incidence in the susceptible population declining by 4.5% per year. As incidence declined early in the 1900s, the average age at infection increased, leading to a paradoxical increase in the incidence of icteric infection followed by a slow decline. The model estimated approximately 270 000 (range: 190 000–360 000) infections annually from 1980 to 1999, 10.4 times the number of hepatitis A cases actually reported during this period. More than half of these infections occurred in children who were younger than 10 years, most of which would have been clinically unrecognizable as hepatitis.

Conclusions. These results suggest a large reservoir of infection in children and that interruption of transmission in children may substantially reduce incidence of hepatitis A overall.
Jaundice as an Early Diagnostic Sign of Urinary Tract Infection in Infancy
Authors: Garcia Francisco J. , Nager Alan L.
Published: August 2004

Objective. Urinary tract infections (UTIs) are a common clinical problem in febrile infants younger than 8 weeks old, with a prevalence between 5% and 11%. Previous studies have noted that jaundice may be one of the first signs of a bacterial infection in infants. Our goal was to determine the incidence of UTIs in asymptomatic, jaundiced infants younger than 8 weeks old and to determine which historical and laboratory parameters are associated with UTIs.

Methods. We prospectively evaluated asymptomatic, jaundiced infants younger than 8 weeks old for evidence of a UTI (defined as >10 000 colony-forming units per milliliter of a single pathogen, obtained by bladder catheterization). A serum fractionated bilirubin level was obtained on all study patients. Detailed questionnaires were completed, which included demographic information, prenatal, intrapartum, and postnatal events.

Results. Twelve (7.5%) of 160 infants had a UTI (95% confidence interval: 3.9%–12.7%). Isolated organisms included Escherichia coli, Enterobacter cloacae, Enterococcus, Klebsiella pneumoniae, group B Streptococcus, Streptococcus viridans, and Staphylococcus aureus. Patients with the onset of jaundice after 8 days of age had a higher incidence of UTI, 6 (50%) of 12 infants in the positive culture group, versus 15 (10%) of 148 infants in the negative culture group. Abnormal urinalysis and microscopy results were noted in 5 (42%) of 12 infants with a UTI, and 6 (55%) of 11 infants had abnormal renal ultrasound results.

Conclusion. A UTI was found in 7.5% of asymptomatic, afebrile, jaundiced infants younger than 8 weeks old. In addition, infants with the onset of jaundice after 8 days of age or patients with an elevated conjugated bilirubin fraction were more likely to have a UTI. Therefore, we recommend that testing for a UTI be included as part of the evaluation in asymptomatic, jaundiced infants presenting to the emergency department.
Efficacy and Safety of Tolazoline for Treatment of Severe Hypoxemia in Extremely Preterm Infants
Authors: Nuntnarumit Pracha , Korones Sheldon B. , Yang Wenjian , Bada Henrietta S.
Published: August 2004

Objective. To determine the efficacy of tolazoline as a rescue treatment for hypoxemia in preterm infants with respiratory distress syndrome.

Methods. Retrospective chart review on case series of infants weighing <750 g at birth who received tolazoline during a severe hypoxemic episode while receiving maximal ventilator support for respiratory distress syndrome. A slow bolus infusion of low dose tolazoline (0.5 mg–2 mg/kg) mixed with plasmanate or normal saline (10 mL/kg) was administered. Outcome measures evaluated included an increase in Pao2 ≥20 mm Hg from pretreatment value and an increase in oxygen saturation to ≥90%.

Results. Forty-three infants with a mean gestational age and birth weight of 24 weeks and 581 g, respectively, received tolazoline. All infants were mechanically ventilated and required a fraction of inspired oxygen of 1.0. Oxygenation improved in 72% (31/43) of infants with a tolazoline dose of 0.5 to 1.0 mg/kg. Of those who responded, Pao2 values (mean ± standard deviation) pretolazoline and posttolazoline were 32 ± 7.5 mm Hg and 156 ± 114.9 mm Hg, respectively. In all responders, oxygen saturation increased to ≥90% within 30 minutes of tolazoline administration. Improvement in pH, pCO2, oxygenation index, and mean airway pressure was also noted. Among nonresponders, pH decreased and pCO2 increased after tolazoline. Minimal change in blood pressure was noted in both responders and nonresponders. Heart rate decreased by 19 beats per minute among nonresponders compared with an increase of 3 beats per minute in those who responded to tolazoline.

Conclusion. Tolazoline is an effective treatment of severe resistant hypoxemia in preterm infants who are already on vigorous ventilatory support.
Nebulized Budesonide Inhalation Suspension Compared With Cromolyn Sodium Nebulizer Solution for Asthma in Young Children: Results of a Randomized Outcomes Trial
Authors: Leflein Jeffrey G. , Szefler Stanley J. , Murphy Kevin R. , Fitzpatrick Sherahe , Cruz-Rivera Mario , Miller Christopher J. , Smith Joseph A.
Published: August 2004

Objective. The availability of antiinflammatory asthma medications for infants and young children has been limited. The objective of this study was to compare effects of nebulized budesonide inhalation suspension and cromolyn sodium nebulizer solution on asthma-related health outcomes in young children with asthma.

Methods. We conducted a randomized, parallel-group, 52-week, open-label study in 36 US clinical sites. Patients included 335 children who were 2 to 6 years of age and had persistent asthma that had been treated with at least 1 long-term control medication; 287 children (86%) completed the study. Patients received budesonide inhalation suspension, 0.5 mg daily (n = 168), or cromolyn sodium nebulizer solution, 20 mg 4 times daily (n = 167), for 8 weeks, followed by dose titration at the investigator’s discretion. The main outcome measure was the rate of asthma exacerbations over 52 weeks. Secondary measures included times to first asthma exacerbation and first use of additional asthma therapy, asthma symptom scores, rescue medication use, and health care resource use.

Results. The budesonide group had a mean (median) asthma exacerbation rate of 1.23 (0.99) per year compared with 2.41 (1.85) for the cromolyn group, significantly longer times to first exacerbation and first use of additional long-term asthma medication, greater improvements in asthma symptom scores, reduced use of rescue medication, and fewer urgent care visits. Both treatments were well tolerated.

Conclusions. Budesonide inhalation suspension was more effective than nebulized cromolyn sodium in young children with persistent asthma. Both treatments were well tolerated with similar adverse event profiles.
A Randomized, Clinical Trial of Oral Midazolam Plus Placebo Versus Oral Midazolam Plus Oral Transmucosal Fentanyl for Sedation During Laceration Repair
Authors: Klein Eileen J. , Diekema Douglas S. , Paris Carolyn A. , Quan Linda , Cohen Morty , Seidel Kristy D.
Published: August 2004

Objective. To determine whether a combination of oral transmucosal fentanyl (Fentanyl Oralet, Abbott Laboratories, North Chicago, IL) plus oral midazolam has an acceptable safety profile and is more effective than oral midazolam alone for sedation during laceration repair in a pediatric emergency department (ED).

Methods. Randomized, double-blind, placebo-controlled, clinical trial. Patients between 2 and 8 years of age who weighed >10 kg and presented to the ED with a laceration in need of repair under sedation were eligible for inclusion. All patients received oral midazolam (0.5 mg/kg; maximum dose 10 mg) and either fentanyl (5–10 μg/kg) or placebo in oralet form. Data collected every 5 minutes included the following: heart rate, oxygen saturation, respiratory rate, pain as measured on a Children’s Hospital of Eastern Ontario Pain Score (CHEOPS) scale (range: 4–13), and an activity scale (range: 1–5). Effectiveness of sedation was measured by CHEOPS and activity scores compared between the treatment groups.

Results. Fifty-one patients were randomized to receive oral midazolam plus fentanyl (N = 28) or oral midazolam plus placebo (N = 23). Age, weight, gender, or baseline pain and activity scores did not differ between the 2 groups. Seven patients in the fentanyl group vomited compared with 0 patients in the placebo group. Three patients in the fentanyl group and no patients in the placebo group had brief oxygen saturation below 93% on room air. The mean pain score within 5 minutes of the start of the procedure did not differ between the 2 groups (fentanyl group, 9.4 versus placebo group, 8.8). Mean activity scores within 5 minutes of the start of the procedure were also similar (fentanyl group, 4.3 versus placebo group, 4.3).

Conclusions. The addition of oral transmucosal fentanyl to oral midazolam did not improve pain or activity scores in pediatric patients given sedation for laceration repair. Patients who received Fentanyl Oralet suffered significantly more side effects despite the relatively low doses administered in this study. Oral transmucosal fentanyl should not be used for procedural sedation in the ED.
Effectiveness and Efficacy of Zinc for the Treatment of Acute Diarrhea in Young Children
Authors: Strand Tor Arne , Chandyo Ram Krisna , Bahl Rajiv , Sharma Pushpa Raj , Adhikari Ramesh Kant , Bhandari Nita , Ulvik Rune Johan , Mølbak Kåre , Bhan Maharaj Krishan , Sommerfelt Halvor
Published: August 2004

Intervention trials have shown that zinc is efficacious in treating acute diarrhea in children of developing countries. In a randomized, placebo-controlled trial, we assessed the effectiveness and efficacy of giving 3 Recommended Daily Allowances of elemental zinc to 6- to 35-month-old children with acute diarrhea.

Methods. Seventeen hundred ninety-two cases of acute diarrhea in Nepalese children were randomized to 4 study groups. Three groups were blinded and the children supplemented daily by field workers with placebo syrup, zinc syrup, or zinc syrup and a massive dose of vitamin A at enrollment. The fourth group was open and the caretaker gave the children zinc syrup daily. Day-wise information on morbidity was obtained by household visits every fifth day.

Results. The relative hazards for termination of diarrhea were 26% (95% confidence interval [CI]: 8%, 46%), 21% (95% CI: 4%, 38%), and 19% (95% CI: 2%, 40%) higher in the zinc, zinc-vitamin A, and zinc-caretaker groups, respectively, than in the placebo group. The relative risks of prolonged diarrhea (duration >7 days) in these groups were 0.57 (95% CI: 0.38, 0.86), 0.53 (95% CI: 0.35, 0.81), and 0.55 (0.37, 0.84); zinc accordingly reduced the risk of prolonged diarrhea with 43% to 47%. Five percent and 5.1% of all syrup administrations were followed by regurgitation in the zinc and zinc-vitamin A group, respectively, whereas this occurred after only 1.3% of placebo administrations. Vomiting during diarrhea was also more common in children receiving zinc.

Conclusions. Three Recommended Daily Allowances of zinc given daily by caretakers or by field workers substantially reduced the duration of diarrhea. The effect of zinc was not dependent on or enhanced by concomitant vitamin A administration.
Occurrence of Omphalocele in Relation to Maternal Multivitamin Use: A Population-Based Study
Authors: Botto Lorenzo D. , Mulinare Joseph , Erickson J. David
Published: August 2004

Objective. We evaluated the association between mothers’ use of multivitamin supplements and their infants’ risk for omphalocele, a congenital anomaly of the abdominal wall. Omphalocele can occur in certain multiple congenital anomaly patterns with neural tube defects, for which a protective effect of multivitamins with folic acid has been demonstrated.

Methods. We used data from a population-based case-control study of infants born from 1968–1980 to mothers residing in metropolitan Atlanta. Case-infants with nonsyndromic omphalocele (n = 72) were actively ascertained from multiple sources. Control-infants (n = 3029), without birth defects, were selected from birth certificates by stratified random sampling.

Results. Compared with no use in the periconceptional period, periconceptional use of multivitamin supplements (regular use from 3 months before pregnancy through the first trimester of pregnancy) was associated with an odds ratio for nonsyndromic omphalocele of 0.4 (95% confidence interval [CI]: 0.2–1.0). For the subset comprising omphalocele alone or with selected midline defects (neural tube defects, hypospadias, and bladder/cloacal exstrophy), the odds ratio was 0.3 (95% CI: 0.1–0.9). These estimates were similar when the reference group also included women who began using multivitamins late in pregnancy (during the second or third month of pregnancy). The small number of participants limited the precision of subgroup analyses and translated into wide confidence intervals that included unity.

Conclusions. Periconceptional multivitamin use was associated with a 60% reduction in the risk for nonsyndromic omphalocele. These findings await replication from additional studies to confirm the findings, generate more precise estimates, and detail possible mechanisms of actions.