bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mevalonate Kinase Deficiency: Enlarging the Clinical and Biochemical Spectrum
Authors: Prietsch Viola , Mayatepek Ertan , Krastel Hermann , Haas Dorothea , Zundel Dorothee , Waterham Hans R. , Wanders Ronald J.A. , Gibson K. Michael , Hoffmann Georg F. 
Published: August 2004

Objective. Mevalonic aciduria as a result of mevalonate kinase deficiency is an inborn error of cholesterol biosynthesis characterized by dysmorphology, psychomotor retardation, progressive cerebellar ataxia, and recurrent febrile crises, usually manifesting in early infancy, accompanied by hepatosplenomegaly, lymphadenopathy, arthralgia, and skin rash. The febrile crises are similar to those observed in hyperimmunoglobulinemia D and periodic fever syndrome (HIDS). Pathogenic mutations in the mevalonate kinase gene in both disorders have demonstrated a common genetic basis. Our aim was to describe the clinical picture of adolescent patients with mevalonate kinase deficiency and to expand the clinical and biochemical spectrum of mevalonate kinase deficiency, particularly with regard to HIDS.Methods. We report the clinical history and biochemical findings of 3 patients with mevalonic aciduria.Results. In 2 siblings with mevalonic aciduria, a 15-year-old girl and a 14-year-old boy, the phenotype shifted with age. Ataxia has become the predominant clinical manifestation, whereas the febrile attacks occur less frequently but as yet have not disappeared. Both of them show marked elevations of immunoglobulin D (IgD). Psychomotor development is retarded but not regressive. Short stature developed in both patients. Additional findings include the development of retinal dystrophy and cataracts in both of them. The third patient is a 6-year-old boy who presented at the age of 5 years with cerebellar ataxia and retinal dystrophy. He is different from all known patients with mevalonic aciduria because of the mild neurologic involvement and because he has never developed febrile crises. In addition, levels of IgD were repeatedly normal.Conclusion. The clinical and biochemical spectrum of patients with mevalonic aciduria is heterogeneous. Manifestations of the disease seem to be age dependent, as evident from this first report of adolescent patients. In patients who survive infancy, short stature, ataxia caused by cerebellar atrophy, and ocular involvement with retinal dystrophy become predominant findings. Recurrent febrile crises seem to diminish with increasing age and may not even be an obligatory finding. Elevation of IgD is most likely a secondary phenomenon that seems to be linked to recurrent febrile crises.
Risk Factors for Unlicensed and Off-Label Drug Use in Children Outside the Hospital
Authors: Schirm Eric , Tobi Hilde , de Jong-van den Berg Lolkje T.W. 
Published: August 2004

Objective. To establish risk factors of unlicensed and off-label drug use by children outside the hospital.
Methods. A cross-sectional study based on 66 222 pharmacy dispensing records for the year 2000 was performed in the northern part of the Netherlands. All prescriptions were divided into the following categories: unlicensed (no product license), off-label (licensed drugs used outside the terms of the product license), and on-label (licensed drugs used according to the product license). For identifying possible problem areas, the proportions of unlicensed and off-label drug use were determined per age group (0–1, 2–5, 6–11, or 12–16 years) and per drug group. For all systemic drugs, a logistic regression was done that models the odds of receiving an unlicensed or off-label prescription as a function of several possible risk factors.
Results. Unlicensed drug use in Dutch children is the highest among 0 to 1-year-olds, and off-label drug use is the highest among 12- to 16-year-olds. Drug groups with highest percentages of unlicensed and off-label drug use were ophthalmologicals/otologicals (80.7% of all prescriptions in this group), blood and blood-forming organs (mainly vitamin K for breastfed newborns; 75.7%), cardiovascular drugs (74.7%), and dermatologicals (73.3%). Prescriptions by specialists (outpatient), prescriptions for new drugs, prescriptions for drugs with a low use in the pediatric population, and prescriptions for infants were risk factors for using a systemic drug unlicensed or off-label.
Conclusion. Efforts to improve pediatric labeling are important and need full support. The present results can be used to focus these efforts.
Inadequate Supervision as a Cause of Injury Deaths Among Young Children in Alaska and Louisiana
Authors: Landen Michael G. , Bauer Ursula , Kohn Melvin 
Published: August 2004

Objective. Inadequate supervision of children has contributed to injuries. However, the association of inadequate supervision with injury events in children has not been quantified. The purpose of this study was to describe and quantify the role of inadequate supervision of children in injury deaths.Methods. Injury deaths among children aged 0 to 6 years in Alaska during 1993 to 1995 and Louisiana during 1994 were classified using 10 child safety standards to assess the role of parent/caregiver supervision in the circumstances of injury death.Results. The leading categories of injury death for both states combined were motor vehicle injury and fire-related injury. Of the classifiable injury deaths in both states (157 [77%] of 203 deaths), the most commonly violated safety standard was “children should be supervised by a responsible care provider” (64 deaths [41%]). Of these deaths, the caregiver was absent in 38%, and the caregiver increased the danger to the child in 17%. Male injury deaths more typically involved a supervision standard violation. Drowning and pedestrian deaths typically involved a supervision standard violation, whereas asphyxiation, homicide, and occupant motor vehicle injury deaths did not.Conclusion. Alaska and Louisiana child injury deaths were mostly attributed to preventable violations of 10 child safety standards, most commonly the supervision standard. The methods in this report were useful in identifying target populations and causes of death, which can be used to plan and implement interventions to improve supervision of children.
Can Changes in Clinical Practice Decrease the Incidence of Severe Retinopathy of Prematurity in Very Low Birth Weight Infants?
Authors: Chow Lily C. , Wright Kenneth W. , Sola Augusto ,   the CSMC Oxygen Administration Study Group
Published: August 2004

Objective. A wide variability in the incidence of severe retinopathy of prematurity (ROP) is reported by different centers. The altered regulation of vascular endothelial growth factor from repeated episodes of hyperoxia and hypoxia is 1 important factor in the pathogenesis of ROP. Strict management of O2 delivery and monitoring to minimize these episodes may be associated with decreased rates of ROP. The objective of this study was to compare the incidence of and need for surgery for severe ROP (stages ≥3) in infants of 500 to 1500 g birth weight before and after the implementation of a new clinical practice of O2 management in a large level 3 neonatal intensive care unit (NICU).Methods. An oxygen management policy that included strict guidelines in the practices of increasing and weaning of fraction of inspired oxygen (Fio2) and the monitoring of O2 saturation parameters in the delivery room, during in-house transport of infants to the NICU, and throughout hospitalization was implemented in April 1998. The main objectives were to monitor oxygenation levels more precisely and to avoid hyperoxia and repeated episodes of hypoxia-hyperoxia in very low birth weight infants. Included in the policy were equipment for monitoring, initiation of monitoring at birth, avoidance of repeated increases and decreases of the Fio2, minimization of “titration” of Fio2, modification of previously used alarm limits, and others. After an educational process, each staff member signed an agreement stating understanding of and future compliance with the guidelines. Examinations were performed by experienced ophthalmologists following international classification and American Academy of Pediatrics recommendations. ROP data from January 1997 to December 2002 for infants of 500 to 1500 g were analyzed as usual and also have been reported to Vermont Oxford Network since 1998.Results. The incidence of ROP 3 to 4 at this center decreased consistently in a 5-year period from 12.5% in 1997 to 2.5% in 2001. The need for ROP laser treatment decreased from 4.5% in 1997 to 0% in the last 3 years.Conclusion. We observed a significant decrease in the rate of severe ROP in very low birth weight infants in association with an educational program provided to all NICU staff and the implementation and enforcement of clinical practices of O2 management and monitoring. Although several confounders cannot be excluded, it is likely that differences in these clinical practices may be, at least in part, responsible for the documented intercenter variability in rates of ROP.
Safety Profile of Frequent Short Courses of Oral Glucocorticoids in Acute Pediatric Asthma: Impact on Bone Metabolism, Bone Density, and Adrenal Function
Authors: Ducharme Francine M. , Chabot Gilles , Polychronakos Constantin , Glorieux Francis , Mazer Bruce 
Published: August 2004

Objective. Our study was designed to establish in children with asthma the safety profile of repeated short courses of oral glucocorticoids on bone mineralization and metabolism and adrenal function.Methods. This cross-sectional study compared the bone density, bone metabolism, and adrenal function of children who were and were not exposed to bursts of oral glucocorticoids. Children were considered exposed when, in the preceding year, they received ≥2 courses of oral glucocorticoids and were prescribed the same therapy for the index exacerbation. Children were considered unexposed when they had no exposure to oral glucocorticoids and were not prescribed any for the index exacerbation. Indices of bone metabolism were measured during the subsequent month. Cortisol responses to adrenocorticotrophic hormone stimulation and bone density were assessed 30 days after the index exacerbation.Results. Eighty-three children (48 exposed, 35 unexposed) aged 2 to 17 years were enrolled. The median exposure level was 4 courses (range: 3–11) in the preceding year. Among exposed children, a transient decrease in serum osteocalcin was observed at the end of the 5-day course with a return to baseline by 30 days; no change was observed in urine pyridinoline cross-links. Mean bone density z score was similar in the exposed (−0.61 ± 1.0 [standard deviation]) and unexposed (−0.67 ± 0.9) groups. No cases of abnormal response to adrenocorticotrophic hormone suggestive of adrenal insufficiency were documented in the exposed (95% confidence interval: 0%–7%) or unexposed (0%–10%) groups.Conclusions. Repeated short courses of oral glucocorticoids in the treatment of asthma seem to be reasonably safe; this practice was not associated with any lasting perturbation in bone metabolism, bone mineralization, or adrenal function.
“They’re Too Smart for That”: Predicting What Children Would Do in the Presence of Guns
Authors: Connor Susan M. , Wesolowski Kathryn L. 
Published: August 2004

Objectives. We examined parents’ beliefs about how children would react to finding guns, with particular emphasis on how parents reasoned about children’s actions.Methods. Based on a randomized telephone survey of Northeast Ohio residents, we focused on the 317 urban and 311 rural respondents who had children 5 to 15 years old in their homes. Respondents were asked about gun ownership and their expectations of how children would react to finding guns. Analysis examined responses in relation to various demographic and socioeconomic variables.Results. All respondents—regardless of gun ownership, geography, race, gender, education level, income, or child age—were equally likely (∼87%) to believe that their children would not touch guns they found. Fifty-two percent of those reasoned that children were “too smart” or “knew better.” Only 40% based their predictions on specific instructions they had given their children. Only 12% (15/122) of owners stored guns locked and unloaded. Only 3 of 13 variables tested were positively associated with safe storage: having a child 5 to 9 years old, having at least a 4-year college education, and having an income ≥$65 000 per year.Conclusion. Results indicate that parental beliefs may effectively relieve adults of responsibility and place the burden on children to protect themselves. The implication for injury prevention is that caregivers’ unrealistic expectations of children’s developmental levels and impulse control may influence storage decisions or the inclination to address gun safety issues with children or other adults with whom children spend time (relatives, playmates’ parents).
Review of Multiple Endocrine Neoplasia Type 2A in Children: Therapeutic Results of Early Thyroidectomy and Prognostic Value of Codon Analysis
Authors: Szinnai Gabor , Meier Christian , Komminoth Paul , Zumsteg Urs W. 
Published: August 2004

Objectives. The aim of this study was first to investigate whether early total thyroidectomy (ETT; 1–5 years of age) can prevent medullary thyroid carcinoma with persistent or recurrent disease (PRD) in pediatric patients with multiple endocrine neoplasia type 2A (MEN-2A) and second, to evaluate the strength of codon analysis in children with MEN-2A as prognostic parameter.
Methods. Case reports and review of the literature for pediatric patients with MEN-2A were conducted. Inclusion criteria were age (0–20 years) and histologic degree of C-cell disease (normal = N, C-cell hyperplasia = CCH, medullary thyroid carcinoma = MTC, metastatic MTC = MMTC). To evaluate therapeutic results of ETT (1–5 years) versus late total thyroidectomy (LTT; 6–20 years), age-dependent histologic stages of C-cell disease and postoperative occurrence of PRD were compared. Prognostic value of specific codons, age-dependent histologic distribution, and long-term outcome were analyzed.
Results. In a total of 260 cases, 42 (16%) underwent ETT, and 218 (84%) underwent LTT. Histologic analysis showed significant difference between ETT versus LTT (57% vs 76%) regarding malignant stage of C-cell disease (of combined rate of MTC and MMTC). Long-term outcome was documented in 74 patients (28%). During a median follow-up period of 2 years (range: 0–15 years), 21 of 65 of the LTT group versus 0 of 9 of the ETT group suffered PRD. Information about codon analysis was available in 150 patients (58%). Mutated codons were c634 (63%), c618 (19%), c620 (9%), and c804 (6%). Codon-related histologic analysis resulted in prognostic differences: 81% of patients with c634-mutation had MCT or MMTC in contrast to c804 (44%), c618 (34%), and c620 (7%). Fifteen of 17 MMTC and 7 of 9 PRD occurred in patients with c634-mutation.
Conclusions. 1) ETT until 5 years of age in MEN-2A gene carriers results in significant reduction of MTC and MMTC in favor of CCH and improved disease-free long-term outcome. 2) Codon analysis is an important prognostic factor. Timing of TT could be individualized based on codon-specific prognosis. Until more detailed knowledge is available, consequent genetic and biochemical screening is mandatory for appropriate individual timing of ETT before age of 5 years.
Scheduled Follow-up After a Pediatric Emergency Department Visit for Asthma: A Randomized Trial
Authors: Zorc Joseph J. , Scarfone Richard J. , Li Yuelin , Hong Travis , Harmelin Melina , Grunstein Lev , Andre Jalal B. 
Published: August 2004

Objectives. Follow-up with a primary care provider (PCP) is recommended after an emergency department (ED) visit for asthma to assess clinical status and develop a management plan to improve future care. However, previous ED-based studies of urban children with asthma have reported low follow-up rates. The objective of this study was to determine whether scheduling an appointment at the time of an ED visit improves PCP follow-up for urban children. A secondary goal was to assess the effect of this intervention on short-term health outcomes and the use of recommended preventive controller medications.
Methods. This randomized trial enrolled a convenience sample of children who were 2 to 18 years old and discharged after treatment for acute asthma in an urban children’s hospital ED. Both intervention and control subjects were instructed to follow up with their PCP within 3 to 5 days. Study staff assisted intervention subjects to call their PCP from the ED and schedule an appointment. When follow-up could not be scheduled, assistance continued after ED discharge by telephone until an appointment date was confirmed. Study outcomes included PCP visits, asthma-related morbidity, and daily use of preventive medication 4 weeks after the ED visit. Outcomes were assessed by telephone interview and confirmed by PCP record review.
Results. A total of 278 eligible subjects were enrolled over 8 months; intervention and control groups were similar by demographic variables and PCP type as well as by asthma history, symptoms, and previous medication use. Only 38% of subjects reported using a daily controller medication, although 70% described persistent asthma symptoms for which these are recommended. For the intervention group, follow-up appointments were successfully obtained during the ED visit for 24% of subjects; when unsuccessful, a median of 3 telephone calls (range: 1–14) were needed to confirm that an appointment had been scheduled. During the 4 weeks after the ED visit, intervention subjects were more likely than controls to follow up with their PCP (64% vs 46%; relative probability for follow-up: 1.4; 95% confidence interval: 1.1–1.7). Study groups did not differ in return ED visits, missed school or work, or the percentage reporting daily use of a controller medication (58% vs 54%) 4 weeks after the ED visit. The median time to the next PCP visit was shorter among intervention subjects (13 vs 54 days).
Conclusions. Scheduling an appointment after an ED visit increased the likelihood that urban children with asthma would follow up with a PCP. An appointment could not be obtained during the ED visit for most children. Other interventions are needed to improve linkage between ED and primary care for asthma and to improve the use of controller medications.
Randomized Clinical Trial of Pacifier Use and Bottle-Feeding or Cupfeeding and Their Effect on Breastfeeding
Authors: Howard Cynthia R. , Howard Fred M. , Lanphear Bruce , Eberly Shirley , deBlieck Elisabeth A. , Oakes David , Lawrence Ruth A. 
Published: August 2004

Objective. To enhance breastfeeding practices, the World Health Organization discourages pacifiers and bottle-feeding. However, the effect of artificial nipples on breastfeeding duration is poorly defined. The effects of 2 types of artificial nipple exposure on breastfeeding duration were evaluated: 1) cupfeeding versus bottle-feeding for the provision of in-hospital supplements and 2) early (2–5 days) versus late (&gt;4 weeks) pacifier introduction.Methods. A total of 700 breastfed newborns (36–42 weeks, birth weight ≥2200 g) were randomly assigned to 1 of 4 intervention groups: bottle/early pacifier (n = 169), bottle/late pacifier (n = 167), cup/early pacifier (n = 185), or cup/late pacifier (n = 179). The cup/bottle intervention was invoked for infants who received supplemental feedings: cup (n = 251), bottle (n = 230). Data were collected at delivery and at 2, 5, 10, 16, 24, 38, and 52 weeks’ postpartum. Intervention effects on breastfeeding duration were evaluated with logistic regression and survival analyses.Results. Supplemental feedings, regardless of method (cup or bottle), had a detrimental effect on breastfeeding duration. There were no differences in cup versus bottle groups for breastfeeding duration. Effects were modified by the number of supplements; exclusive and full breastfeeding duration were prolonged in cup-fed infants given &gt;2 supplements. Among infants delivered by cesarean, cupfeeding significantly prolonged exclusive, full, and overall breastfeeding duration. Exclusive breastfeeding at 4 weeks was less likely among infants exposed to pacifiers (early pacifier group; odds ratio: 1.5; 95% confidence interval: 1.0–2.0). Early, as compared with late, pacifier use shortened overall duration (adjusted hazard ratio: 1.22; 95% confidence interval: 1.03–1.44) but did not affect exclusive or full duration.Conclusions. There was no advantage to cupfeeding for providing supplements to the general population of healthy breastfed infants, but it may have benefitted mother–infant dyads who required multiple supplements or were delivered by cesarean. Pacifier use in the neonatal period was detrimental to exclusive and overall breastfeeding. These findings support recommendations to avoid exposing breastfed infants to artificial nipples in the neonatal period.
Prolonging Small Feeding Volumes Early in Life Decreases the Incidence of Necrotizing Enterocolitis in Very Low Birth Weight Infants
Authors: Berseth Carol Lynn , Bisquera Jennifer A. , Paje Virna U. 
Published: August 2004

Objective. Approximately 90% of infants who develop necrotizing enterocolitis (NEC) do so after being fed. Previous prospective studies have shown that infants given small enteral feedings for the first 7 to 10 days of feeding do not have an increased risk for NEC compared with those given no feedings. Although neonatologists now commonly increase feeding volumes, no study has compared the risk for NEC between infants fed these small volumes and those fed volumes that are increased slowly. The purpose of this study was to compare the risks and benefits of small and increasing feeding volume.
Methods. In a randomized, controlled trial, we randomly assigned 141 preterm infants in the newborn intensive care unit to be fed 10 days using 1 of 2 schedules. One group was fed 20 mL/kg/d for the first 10 study days (minimal). The other group (advancing) was fed 20 mL/kg/d on study day 1; feeding volume was increased by 20 mL/kg/d up to 140 mL/kg/d, which was maintained until study day 10. The main outcome measure was incidence of NEC; secondary outcomes were maturation of intestinal motor patterns, time to reach full enteral feedings, and incidence of late sepsis.
Results. The study was closed early because 7 infants who were assigned to advancing feeding volumes developed NEC, whereas only 1 infant fed minimal feeding volumes did, or 10% versus 1.4%. Although infants who were fed minimal volumes established full enteral feeding volumes later than infants who were fed advancing volumes, maturation of intestinal motor patterns and the incidence of late sepsis and feeding intolerance was similar in the 2 groups.
Conclusion. Given that advancing feeding volumes increase the risk of NEC without providing benefits for motor function or feeding tolerance, neonatologists should consider using minimal feeding volumes until future trials assess the safety of advancing feeding volumes.