bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethical Assessment of Clinical Asthma Trials Including Children Subjects
Authors: Coffey M. Justin , Wilfond Benjamin , Ross Lainie Friedman 
Published: August 2004

Background. The inclusion of children with asthma in clinical asthma trials is increasing, including their participation in placebo-controlled trials (PCTs). The objectives of this study are to assess whether children with asthma have been harmed by their participation in PCTs.Methods. Seventy clinical asthma trials involving children published between January 1998 and December 2001 that involved distinct US research populations were identified. Studies were reviewed to determine whether all subjects with more than mild asthma received daily antiinflammatory medication as recommended by national guidelines. Sixty-two clinical asthma trials included data about subject withdrawal and were analyzed for the frequency of asthma exacerbations.Results. Forty-five studies were designed as PCTs and did not require that all subjects with more than mild asthma receive antiinflammatory medications. Of 24 953 subjects, 4653 (19%) for whom data are available withdrew from research, and 1247 subjects (9.4%) withdrew from PCTs due to asthma exacerbations compared with 358 subjects (3.1%) in other trials. In PCTs, subjects withdrew more frequently from the placebo arms than the active-treatment arms and did so more frequently because of an asthma exacerbation (667 or 15% vs 580 or 6.5%). Fifty-two studies enrolled both children and adults, although only 1 performed subset analysis of the children.Conclusions. Subjects enrolled in PCTs of asthma have been exposed to unnecessary risks and harms. Clinical asthma trials involving children and adults do not benefit children as a class because they rarely provide subset analysis of children subjects.
Survival and Long-Term Neurodevelopmental Outcome of Extremely Premature Infants Born at 23–26 Weeks’ Gestational Age at a Tertiary Center
Authors: Hoekstra Ronald E. , Ferrara T. Bruce , Couser Robert J. , Payne Nathaniel R. , Connett John E. 
Published: August 2004

Objective. Long-term outcome, including school-age function, has been infrequently reported in infants born at ages as young as 23–26 weeks’ gestation. The objective of this study is to report outcome on a large cohort of these infants to understand better the risks and factors that affect survival and long-term prognosis.Methods. Records from 1036 infants who were born between January 1, 1986, and December 31, 2000, were analyzed retrospectively by logistic regression to correlate multiple factors with both survival and long-term outcome. A total of 675 surviving infants were analyzed at a mean age of 47.5 months for developmental outcome. A subset of 147 surviving infants who were born before 1991 were followed through school-age years using the University of Vermont Achenbach Child Behavioral Checklist and Teachers Report Form. Longitudinal follow-up was performed comparing 1-year outcome with school-age performance.Results. Gestational age and recent year of birth correlated highly with survival. Maternal nonwhite race, female sex, inborn status, surfactant therapy, single gestation, and secondary sepsis also correlated positively with survival. Normal cranial ultrasound results, absence of chronic lung disease, female sex, cesarean delivery, and increased birth weight correlated favorably with long-term outcome. Infants who were born at 23 weeks were more likely to have severe impairments compared with those who were born at 24–26 weeks. Early follow-up identified most subsequent physical impairments but correlated poorly with school-age function.Conclusions. Survival continues to improve for infants who are born at extremely early gestational ages, but long-term developmental concerns continue to be prevalent. Early outcomes do not reliably predict school-age performance. Strategies that reduce severe intraventricular hemorrhage and chronic lung disease will likely yield the best chances to improve long-term outlook.
A Randomized Trial of Calcium Supplementation for Childhood Lead Poisoning
Authors: Markowitz Morri E. , Sinnett Mark , Rosen John F. 
Published: August 2004

Objective. Lead (Pb) poisoning remains a common disease among children despite successful public health efforts that have reduced its prevalence. Treatment options for children with blood Pb levels (BPbs) &lt;45 μg/dL are limited because chelation therapy is generally not indicated. Calcium (Ca) and Pb interactions are well documented. Competition for binding to Ca-binding proteins may underlie a mechanism for Pb absorption. The purpose of this study was to determine the role, if any, of supplemental Ca at reducing BPbs in moderately poisoned children.Methods. Children aged 1 to 6 years with BPbs 10 to 45 μg/dL were enrolled in a double-blinded, placebo-controlled trial of the effects of Ca supplementation on BPbs. Children received either a Ca-containing liquid or an indistinguishable placebo. Dosage was adjusted biweekly on the basis of responses to a dietary Ca intake questionnaire to reach 1800 mg in the Ca-supplemented group. Samples for BPbs and measures to assess safety were collected before and after 3 months of supplementation and after an additional 3 months of follow-up. Bivariate and multiple regression analyses were performed.Results. A total of 67 of 88 enrolled children with a mean age of 3.6 years completed 3 months of supplementation. There were no statistically significant differences between groups on hematologic and biochemical measures, including serum and urinary Ca, at any time points. The average compliance rate was estimated to be 80% for each group during the 3-month supplementation period.Conclusions. At enrollment, the average daily Ca intake in this group of inner-city children was greater than the recommended daily intake for age. Although BPbs declined during a 3-month period in both groups, Ca supplementation aimed at providing 1800 mg of Ca/day had no effect on the change in BPbs. Ca supplementation should not be routinely prescribed for mild to moderately Pb-poisoned children who are dietarily Ca sufficient.
Topical Ciprofloxacin/Dexamethasone Otic Suspension Is Superior to Ofloxacin Otic Solution in the Treatment of Children With Acute Otitis Media With Otorrhea Through Tympanostomy Tubes
Authors: Roland Peter S. , Kreisler Leslie S. , Reese Bradley , Anon Jack B. , Lanier Brent , Conroy Peter J. , Wall G. Michael , Dupre Sheryl J. , Potts Susan , Hogg Gail , Stroman David W. , McLean Celeste 
Published: August 2004

Objective. To determine the efficacy and safety of topical ciprofloxacin/dexamethasone otic suspension compared with ofloxacin otic solution in the treatment of acute otitis media with otorrhea through tympanostomy tubes (AOMT) in pediatric patients.
Methods. This multicenter, prospective, randomized, observer-masked, parallel-group study was conducted at 39 sites in 599 children aged ≥6 months to 12 years with an AOMT episode of ≤3 weeks’ duration. The mean age of patients was 2.5 years (standard deviation: 2.37 years). Patients received either ciprofloxacin 0.3%/dexamethasone 0.1% otic suspension 4 drops twice daily for 7 days or ofloxacin 0.3% otic solution 5 drops twice daily for 10 days. Clinical signs and symptoms of AOMT were evaluated at clinic visits on days 1 (baseline), 3 (on therapy), 11 (end of therapy), and 18 (test of cure). A patient diary was used to measure time to cessation of otorrhea. Principal pretherapy pathogens included Streptococcus pneumoniae (16.8%), Staphylococcus aureus (13.0%), Pseudomonas aeruginosa (12.7%), Haemophilus influenzae (12.4%), S epidermidis (10.2%), and Moraxella catarrhalis (4.1%).
Results. Ciprofloxacin/dexamethasone is superior to ofloxacin for clinical cure (90% vs 78%) and microbiologic success (92% vs 81.8%) at the test-of-cure visit, produces fewer treatment failures (4.4% vs 14.1%), and results in a shorter median time to cessation of otorrhea (4 days vs 6 days). Ciprofloxacin/dexamethasone treatment is also superior to improvement in clinical response by visit, absence of otorrhea by visit, and reduction of otorrhea volume by visit. Both topical otic preparations are safe and well tolerated in pediatric patients. No change in speech recognition threshold or decrease in hearing from baseline, based on audiometric testing, was noted with either regimen.
Conclusion. Topical ciprofloxacin/dexamethasone treatment is superior to topical ofloxacin in the treatment of AOMT.
Deep Venous Thrombosis in Children With Diabetic Ketoacidosis and Femoral Central Venous Catheters
Authors: Worly Julia M. , Fortenberry James D. , Hansen Inger , Chambliss C. Robert , Stockwell Jana 
Published: August 2004

Objective. To describe findings of deep venous thrombosis (DVT) in association with femoral central venous catheter (CVC) placement for intensive fluid management in children with diabetic ketoacidosis (DKA) secondary to type 1 diabetes.Design. Retrospective cohort study.Setting. Pediatric intensive care unit (PICU) of a children’s referral medical center.Patients. DKA patients from 1998 to 2002 of children with DKA with and without CVC placement. DKA patients were also compared with all PICU patients with CVC. CVC DVT was defined as ipsilateral leg swelling with CVC placement, confirmed by radiographic study, and persisting after CVC removal.Measurements and Main Results. Of 113 DKA PICU patients, 6 (5.3%) required femoral CVC for initial management. Three of these DKA/CVC patients developed ipsilateral DVT within 48 hours of CVC placement. All 3 patients required long-term therapy with low molecular weight heparin for persistent leg swelling. DKA/CVC patients with DVT were younger (median age: 10.5 months) than DKA/CVC patients without DVT. The number of DKA/CVC patients with DVT (1.4%) was significantly greater than for all femoral non-DKA/CVC patients. DKA/CVC patients were also significantly more likely to have DVT than age-matched shock/CVC patients. They also had significantly higher glucose, corrected sodium concentrations, and lower pH and serum bicarbonate than did age-matched shock/CVC patients.Conclusions. Femoral CVC placement is infrequently needed in pediatric DKA patients but can be associated with DVT. Femoral CVCs should be avoided in DKA patients or removed as soon as possible. DVT prophylaxis should be considered if a CVC is required.
Reference Values for Amplitude-Integrated Electroencephalographic Activity in Preterm Infants Younger Than 30 Weeks’ Gestational Age
Authors: Olischar Monika , Klebermass Katrin , Kuhle Stefan , Hulek Margot , Kohlhauser Christina , Rücklinger Ernst , Pollak Arnold , Weninger Manfred 
Published: August 2004

Objective. To prospectively investigate the development of amplitude-integrated electroencephalographic (aEEG) activity during the first 2 weeks of life in neurologically normal and clinically stable preterm infants &lt;30 weeks’ gestational age (GA).
Patients and Methods. Infants with a GA of &lt;30 weeks admitted to the neonatal intensive care unit of the Vienna University Children’s Hospital (Vienna, Austria) were studied prospectively by using aEEG and cranial ultrasound. Clinically stable infants without clinical or sonographic evidence of neurologic abnormalities were eligible for inclusion in the reference group. The distribution of 3 background aEEG activity patterns (discontinuous low-voltage, discontinuous high-voltage, and continuous), presence of sleep-wake cycles, and number of bursts per hour in the reference group were determined by visual analysis.
Results. Seventy-five infants (median GA: 27 weeks; range: 23–29 weeks) were eligible for inclusion in the reference group and had aEEG recordings during the first 2 weeks of life available. Analysis of aEEG background activity showed that with higher GA the relative amount of continuous activity increased while discontinuous patterns decreased. The number of bursts per hour decreased with increasing GA. Cyclical changes in aEEG background activity resembling early sleep-wake cycles were observed in all infants.
Conclusions. Normal values for aEEG background activity were determined in preterm infants &lt;30 weeks’ GA. Clinically stable and neurologically normal preterm infants exhibit at least 2 different patterns of aEEG activity. There is a correlation between the GA and the relative duration of continuous aEEG activity.
Inflammatory Cytokine Profile in Children With Severe Acute Respiratory Syndrome
Authors: Ng Pak C. , Lam Christopher W.K. , Li Albert M. , Wong Chun K. , Cheng Frankie W.T. , Leung Ting F. , Hon Ellis K.L. , Chan Iris H.S. , Li Chi K. , Fung Kitty S.C. , Fok Tai F. 
Published: August 2004

Objective. To study the inflammatory cytokine profile in children with severe acute respiratory syndrome (SARS) and to investigate whether monoclonal antibody to tumor necrosis factor-α (TNF-α) could be considered for treatment of these patients.Methods. Plasma inflammatory cytokine concentrations (interleukin [IL]-1β, IL-6, IL-8, IL-10, IL-12p70, and TNF-α) were monitored longitudinally on admission, immediately before corticosteroids, and 1 to 2 days and 7 to 10 days after the drug treatment in a cohort of pediatric patients (n = 8) with virologic confirmed SARS-associated coronavirus infection. None of the patients required mechanical ventilation or intensive care treatment. All children except 1 (patient 3) received corticosteroids.Results. Plasma IL-1β levels (excluding patient 3) were substantially elevated immediately before (range: 7–721 ng/L) and 7 to 10 days after (range: 7–664 ng/L) corticosteroid treatment. In contrast, the plasma concentrations of other key proinflammatory cytokines, including IL-6 and TNF-α, were not overtly increased in any of the patients throughout the course of illness. In addition, plasma IL-10 concentration was significantly lower 1 to 2 days and 7 to 10 days after corticosteroid treatment, compared with the immediate pretreatment level. Similarly, plasma IL-6 and IL-8 concentrations were significantly decreased 7 to 10 days after the drug treatment.Conclusions. Pediatric SARS patients have markedly elevated circulating IL-1β levels, which suggests selective activation of the caspase-1-dependent pathway. Other key proinflammatory cytokines, IL-6 and TNF-α, showed only mildly elevated levels at the initial phase of the illness. The current evidence does not support the use of TNF-α monoclonal antibody in this group of children.
Age at First Measles-Mumps-Rubella Vaccination in Children With Autism and School-Matched Control Subjects: A Population-Based Study in Metropolitan Atlanta
Authors: DeStefano Frank , Bhasin Tanya Karapurkar , Thompson William W. , Yeargin-Allsopp Marshalyn , Boyle Coleen 
Published: August 2004

Objective. To compare ages at first measles-mumps-rubella (MMR) vaccination between children with autism and children who did not have autism in the total population and in selected subgroups, including children with regression in development.
Methods. A case-control study was conducted in metropolitan Atlanta. Case children (N = 624) were identified from multiple sources and matched to control children (N = 1824) on age, gender, and school. Vaccination data were abstracted from immunization forms required for school entry. Records of children who were born in Georgia were linked to Georgia birth certificates for information on maternal and birth factors. Conditional logistic regression was used to estimate odds ratios (ORs).
Results. The overall distribution of ages at MMR vaccination among children with autism was similar to that of matched control children; most case (70.5%) and control children (67.5%) were vaccinated between 12 and 17 months of age. Similar proportions of case and control children had been vaccinated before 18 or before 24 months. No significant associations for either of these age cutoffs were found for specific case subgroups, including those with evidence of developmental regression. More case (93.4%) than control children (90.6%) were vaccinated before 36 months (OR: 1.49; 95% confidence interval: 1.04–2.14 in the total sample; OR: 1.23; 95% confidence interval: 0.64–2.36 in the birth certificate sample). This association was strongest in the 3- to 5-year age group.
Conclusions. Similar proportions of case and control children were vaccinated by the recommended age or shortly after (ie, before 18 months) and before the age by which atypical development is usually recognized in children with autism (ie, 24 months). Vaccination before 36 months was more common among case children than control children, especially among children 3 to 5 years of age, likely reflecting immunization requirements for enrollment in early intervention programs.
Perception of Child Vulnerability Among Mothers of Former Premature Infants
Authors: Allen Elizabeth C. , Manuel Janeen C. , Legault Claudine , Naughton Michelle J. , Pivor Carol , O’Shea T. Michael 
Published: August 2004

Objectives. Parents of premature infants often perceive their infants as medically vulnerable. High parental perception of child vulnerability (PPCV) is associated with disproportionately high health care utilization. The objectives of this study were to determine whether higher PPCV is correlated with worse developmental outcome in premature infants at 1-year adjusted age and to identify factors, present at neonatal discharge, that predict high PPCV.Methods. This prospective cohort study assessed mothers of 116 premature infants who were ≤32 weeks’ gestation and required supplemental oxygen at 36 weeks postmenstrual age. At neonatal discharge, mothers completed the Spielberger State Anxiety Inventory, Beck Depression Inventory, Impact on Family Scale, Life Orientation Test, General Health Survey, and Medical Outcomes Study social support survey. At 1-year adjusted age, child development was assessed using the Bayley Scales of Infant Development and Vineland Adaptive Behavior Scales, and mothers completed the Vulnerable Child Scale, a 16-item self-report measure of PPCV. Chart review was performed to determine the presence or absence of specific indicators of medical vulnerability at 1-year adjusted age.Results. Mean infant gestational age and birth weight were 26.5 ± 2.5 weeks and 894 ± 287 g. A total of 69% of mothers were white, and 78% were high school graduates. Higher PPCV (lower Vulnerable Child Scale score) was correlated with lower scores on the Vineland Adaptive Behavior Composite and Bayley Psychomotor Developmental Index but not on the Bayley Mental Developmental Index. After controlling for the presence of 1 or more indicators of medical vulnerability, higher PPCV was still correlated with lower adaptive development. This correlation was stronger in the group of children with no indicators of medical vulnerability. In univariate analyses, higher PPCV was predicted by nonfirstborn status; longer neonatal hospitalization; higher maternal anxiety and depression; greater impact of the illness on the family; and lower maternal optimism, life satisfaction, and social support. PPCV was not associated with maternal age, education, marital status, income, or ethnicity or with child gender, gestational age, birth weight, or length of mechanical ventilation. A linear regression model containing all variables significant at the univariate level explained 29% of the variance in PPCV. Maternal anxiety was the only variable that was statistically significant in the full model.Conclusions. Higher PPCV is associated with worse developmental outcome in premature infants at 1-year adjusted age. Maternal anxiety at neonatal discharge predicts later high PPCV. Interventions to prevent or decrease PPCV in premature infants should be targeted at parents who are more anxious at hospital discharge.
Preferences and Willingness to Pay for Health States Prevented by Pneumococcal Conjugate Vaccine
Authors: Prosser Lisa A. , Ray G. Thomas , O’Brien Megan , Kleinman Ken , Santoli Jeanne , Lieu Tracy A. 
Published: August 2004

Objective. To measure parents’ and other adults’ values for preventing disease associated with pneumococcal infection and to evaluate how including these values changes the economic appraisal of pneumococcal conjugate vaccine.Methods. Data on preferences and willingness to pay to reduce risk of illness were collected for 6 illnesses that are preventable by pneumococcal conjugate vaccine (simple otitis media, complex otitis media, moderate pneumonia, severe pneumonia, bacteremia, and meningitis) and 1 vaccine-related adverse event (fever and fussiness after vaccine). Interviews were conducted with 2 groups of respondents: 1) parents of children who had experienced 1 or more of the outcomes described in the survey (n = 101) and 2) a US community sample (n = 109). The 30-minute telephone interview used modified time trade-off questions and willingness-to-pay questions. Values from the interview were incorporated in an existing decision-analytic model that simulated the cost-effectiveness and cost-benefit of pneumococcal conjugate vaccine in a hypothetical cohort of newborns.Results. Among parents, the median amount of time that respondents said that they would be willing to trade to avoid diseases ranged from 0 days for otitis media to 1 year for severe pneumonia and 2 years for meningitis. Among the US community sample, the median amounts of time traded were higher, ranging from 7 days for otitis media to 3 years for meningitis. Median willingness-to-pay amounts varied from $100 to prevent 1 episode of otitis media and $500 to reduce the risk of meningitis from 21 in 100 000 to 6 in 100 000 and were similar between parents and community members. Incorporating time trade-off amounts into the existing economic model for pneumococcal conjugate vaccine resulted in cost-effectiveness ratios &lt;$10 000 per quality-adjusted life year at a vaccine cost of $58 per dose.Conclusions. Both parents and community members assign relatively high values to preventing meningitis, pneumonia, and complex otitis media. When the value of preventing pneumococcal diseases is incorporated into economic analyses, pneumococcal conjugate vaccine has a cost-effectiveness ratio in the range of other widely used health interventions.
Efficacy of Constraint-Induced Movement Therapy for Children With Cerebral Palsy With Asymmetric Motor Impairment
Authors: Taub Edward , Ramey Sharon Landesman , DeLuca Stephanie , Echols Karen 
Published: August 2004

Objective. Constraint-Induced Movement (CI) therapy has been found to be a promising treatment for substantially increasing the use of extremities affected by such neurologic injuries as stroke and traumatic brain injury in adults. The purpose of this study was to determine the applicability of this intervention to young children with cerebral palsy.
Methods. A randomized, controlled clinical trial of pediatric CI therapy in which 18 children with diagnosed hemiparesis associated with cerebral palsy (7–96 months old) were randomly assigned to receive either pediatric CI therapy or conventional treatment. Pediatric CI therapy involved promoting increased use of the more-affected arm and hand by intensive training (using shaping) of the more-impaired upper extremity for 6 hours/day for 21 consecutive days coupled with bivalved casting of the child’s less-affected upper extremity for that period. Children’s functional upper-extremity skills were assessed in the laboratory (blinded scoring) and at home (parent ratings) just prior, after, and 3 weeks posttreatment. Treated children were followed for 6 months.
Results. Children receiving pediatric CI therapy compared with controls acquired significantly more new classes of motoric skills (9.3 vs 2.2); demonstrated significant gains in the mean amount (2.1 vs 0.1) and quality (1.7 vs 0.3) of more-affected arm use at home; and in a laboratory motor function test displayed substantial improvement including increases in unprompted use of the more-affected upper extremity (52.1% vs 2.1% of items). Benefits were maintained over 6 months, with supplemental evidence of quality-of-life changes for many children.
Conclusion. Pediatric CI therapy produced major and sustained improvement in motoric function in the young children with hemiparesis in the study.