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Status of the Pediatric Clinical Trials Enterprise: An Analysis of the US ClinicalTrials.gov Registry

There are limited data regarding the current status of the pediatric clinical trial enterprise.

Evaluation of the ClinicalTrials.gov data set allows description of the overall portfolio of clinical trials relevant to US children, which was previously not possible. (Read the full article)




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Clinical Utility of Chromosomal Microarray Analysis

Chromosomal microarray analysis offers a superior diagnostic yield over karyotyping for the evaluation of individuals with developmental disabilities. Many third-party payers, however, do not reimburse for microarray testing, citing a lack of evidence that patients benefit from testing.

This study demonstrates that microarray testing frequently identifies conditions that include features requiring specific medical follow-up and that referring physicians respond to abnormal test results with appropriate clinical actions. Microarray testing, therefore, provides direct benefits to patients. (Read the full article)




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Identifying and Treating a Substandard Housing Cluster Using a Medical-Legal Partnership

Social and environmental risks related to substandard housing contribute to adverse health outcomes. Partnerships between the health care and legal systems can help families address such risks and help clinicians understand the legal context of health.

A medical-legal partnership colocated in a pediatric primary care setting identified and treated a large cluster of poor quality, substandard housing. Housing improvements were possible because of strong collaboration between clinicians, attorneys, community partners, and families. (Read the full article)




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The Globalization of Pediatric Clinical Trials

There is concern about the potential exploitation of children who are enrolled into clinical trials in developing and transition countries. Previous studies of globalization have only examined pediatric drug trials, and only 1 study has provided patient-level data by country.

The involvement of developing and transition countries depends on the product or indication under investigation and is greater for vaccines than for drugs or biologicals. Compared with our previous analysis, involvement of these countries in pediatric drug development has decreased. (Read the full article)




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Muscle-enhancing Behaviors Among Adolescent Girls and Boys

Emphasis on muscularity has increased in recent decades. Identifying adolescent populations at risk for unhealthy muscle-enhancing behaviors is of considerable importance, yet recent research in the United States is limited in terms of sample diversity and behaviors of interest.

Muscle-enhancing behaviors were common for both boys and girls, and rates were higher than reported previously. Adolescents in high school, of Asian background, in overweight/obese BMI categories, and involved in sports reported significantly greater use than other youth. (Read the full article)




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Near-Infrared Imaging in Intravenous Cannulation in Children: A Cluster Randomized Clinical Trial

Gaining intravenous access in children can be difficult. Recently, several near-infrared devices have been introduced attempting to support intravenous cannulation by visualizing veins underneath skin. Only one of those devices has been evaluated systemically thus far and results are inconclusive.

Although it was possible to visualize veins with near-infrared in most patients, the VascuLuminator did not improve the success of cannulation. An explanation is that the main problem is probably not localization of the vein but insertion of the cannula. (Read the full article)




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Subclinical Cerebral Edema in Children With Diabetic Ketoacidosis Randomized to 2 Different Rehydration Protocols

Cerebral edema (CE) occurs frequently during treatment of diabetic ketoacidosis (DKA) in children. Severe, life-threatening CE occurs rarely, but subclinical CE is common. Whether the rate of infusion of intravenous fluids influences the occurrence or severity of CE is unknown.

This study demonstrates that the rate of fluid infusion in children with DKA does not substantially affect MRI measures of CE. Studies assessing measures other than edema formation are necessary to determine whether fluid infusion rates influence DKA-related brain injury. (Read the full article)




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A Randomized Clinical Trial of a Web-Based Tobacco Cessation Education Program

Children exposed to second-hand smoke have high rates of hospitalization for respiratory illness. These visits represent a "teachable moment" when parental smokers can be motivated to quit. However, pediatric health care practitioners receive little training in tobacco cessation.

The Web-Based Respiratory Education About Tobacco and Health online training program was effective at increasing the provision of an effective tobacco cessation intervention by pediatric hospital-based respiratory therapists, registered nurses, and nurse practitioners to adult smokers. (Read the full article)




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Interns' Success With Clinical Procedures in Infants After Simulation Training

Pediatric training programs use simulation for procedural skills training. Research demonstrates student satisfaction with simulation training, improved confidence, and improved skills when retested on a simulator. Few studies, however, have investigated the clinical impact of simulation education.

This is the first multicenter, randomized trial to evaluate the impact of simulation-based mastery learning on clinical procedural performance in pediatrics. A single simulation-based training session was not sufficient to improve interns’ clinical procedural performance. (Read the full article)




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Maternal Alcohol Use and Sudden Infant Death Syndrome and Infant Mortality Excluding SIDS

Reductions in infant mortality in the 20th century have not continued. Racial and socioeconomic inequalities in both infant mortality and sudden infant death syndrome (SIDS) persist. Rates of infant mortality in English-speaking countries are higher than the Organisation for Economic Co-operation and Development average.

At least 16.4% of SIDS and 3.4% of infant deaths not classified as SIDS are attributable to maternal alcohol use. Maternal alcohol-use disorder increases the risk of infant mortality through direct effects on the fetus and indirectly through environmental risk factors. (Read the full article)




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Improving Adherence to Otitis Media Guidelines With Clinical Decision Support and Physician Feedback

Expectations are high that electronic health record–based clinical decision support and performance feedback will improve adherence to guidelines by delivering relevant and actionable information to clinicians. Few studies have evaluated these assertions or examined the combined effects of decision support and feedback.

Clinical decision support customized to a patient’s history and presentation and performance feedback are both effective for improving adherence to guidelines for otitis media. However, the combination of the 2 interventions is no better than either delivered alone. (Read the full article)




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Chlorhexidine Cleansing of the Umbilical Cord and Separation Time: A Cluster-Randomized Trial

Chlorhexidine cleansing of the cord can reduce mortality in high-risk settings. Time to separation may increase with topical applications of chlorhexidine; 1 previous community trial quantified this increase and did not measure whether caretakers perceived the delay.

Single and multiple cleansing of the umbilical cord increases time to separation by ~50%, or an average of 2 to 2.5 days. Caretakers were able to detect this difference and expressed dissatisfaction, while still accepting the intervention. (Read the full article)




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Pacifier Restriction and Exclusive Breastfeeding

Pacifiers may interfere with breastfeeding and thus are discouraged until 3 to 4 weeks of life, when they are recommended for sudden infant death syndrome risk reduction. Hospitals are restricting pacifier distribution as part of the Baby-Friendly Hospital Initiative.

We describe a temporal association between reduced exclusive breastfeeding and pacifier restriction. This observation encourages research on breastfeeding promotion and the effects of pacifiers and pacifier restriction on breastfeeding. (Read the full article)




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Evaluation of an Office Protocol to Increase Exclusivity of Breastfeeding

A gap exists with lack of programs to help mothers breastfeed. The 2012 American Academy of Pediatrics' "Policy Statement on Breastfeeding and the Use of Human Milk" re-emphasized breastfeeding as an important public health initiative rather than a lifestyle choice.

Families who receive care in a primary care setting that has implemented a "breastfeeding-friendly" office protocol may have increased rates of exclusive breastfeeding. This study evaluated an accepted clinical protocol in a large, diverse pediatric primary care setting. (Read the full article)




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Cluster (School) RCT of ParentCorps: Impact on Kindergarten Academic Achievement

At least half of the achievement gap for low-income, minority children is present at kindergarten entry; however, there are no population-level early childhood interventions that effectively engage and support families and teachers to ameliorate the impact of adversity on achievement.

This study evaluated ParentCorps, a family-centered, school-based intervention to promote self-regulation and learning for all children entering school in disadvantaged, urban neighborhoods. ParentCorps results in higher kindergarten achievement among low-income, minority children. (Read the full article)




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Incidence of Rash After Amoxicillin Treatment in Children With Infectious Mononucleosis

Antibiotics-induced rash in Epstein-Barr virus acute infectious mononucleosis, especially the aminopenicillins-induced type, was first described during the 1960s, with a reported incidence of 80% to 100%. This phenomenon was not further investigated but is well-established in pediatric textbooks.

The main observation of this study is that rash induced by amoxicillin in confirmed Epstein-Barr virus acute infectious mononucleosis was found at a rate of ~30%, which is much lower than previously reported. (Read the full article)




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Analysis of Pediatric Clinical Drug Trials for Neuropsychiatric Conditions

Neuropsychiatric conditions comprise a substantial and growing disease burden among children. Pharmacotherapy represents an important treatment option for these conditions, although most drugs are not approved for use in children.

Very few drug trials studying neuropsychiatric conditions focus on children. Furthermore, these trials examine and provide pediatric evidence for only a fraction of all available drugs in the treatment of common neuropsychiatric conditions. (Read the full article)




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Effectiveness of Decision Support for Families, Clinicians, or Both on HPV Vaccine Receipt

Despite proven health benefits, human papillomavirus (HPV) vaccination rates are among the lowest of all routine immunizations. No previous large-scale trial has compared the benefit of automated decision support directed at clinicians, families, or both in any context.

We found that a clinician-focused intervention was most effective for initiating the HPV vaccine series, whereas a family-focused intervention supported completion. Decision support directed at both clinicians and families most effectively promotes HPV vaccine series receipt. (Read the full article)




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Pacifier Cleaning Practices and Risk of Allergy Development

Infants with a diverse gut microbial flora are less likely to develop eczema and allergy.

Parental sucking of their infant’s pacifier is associated with a reduced risk of allergy development and an altered oral flora in their child. Transfer of oral microbes from parent to infant via the pacifier might be used in primary prevention. (Read the full article)




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Texting While Driving and Other Risky Motor Vehicle Behaviors Among US High School Students

Distracted driving due to texting while driving (TWD) has emerged as an important teenage safety issue. Previous studies have shown that the self-reported prevalence of TWD among teenagers varies widely.

In 2011, 45% of US high school students aged ≥16 years reported TWD during the past 30 days. TWD was positively associated with other risky motor vehicle behaviors; this association strengthened as frequency of TWD increased. (Read the full article)




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Effect of Early Limited Formula on Duration and Exclusivity of Breastfeeding in At-Risk Infants: An RCT

Public health policy focuses on reducing formula use for breastfed infants during the birth hospitalization. Observational evidence supports this approach, but no previous studies have examined the effect of early use of small volumes of formula on eventual breastfeeding duration.

Use of limited volumes of formula during the birth hospitalization may improve breastfeeding duration for newborns with high early weight loss. Reducing the use of formula during the birth hospitalization could be detrimental for some subpopulations of healthy term newborns. (Read the full article)




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Health of Children Classified as Underweight by CDC Reference but Normal by WHO Standard

Many US children aged 6 to 24 months who would be classified as low weight-for-age by the Centers for Disease Control and Prevention 2000 reference will be classified as normal weight-for-age by the World Health Organization 2006 standard.

Children who will be reclassified from low to normal weight-for-age using the World Health Organization growth standard are at higher risk of adverse health outcomes than children who are not low weight-for-age by the Centers for Disease Control and Prevention reference. (Read the full article)




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Access to Digital Technology Among Families Coming to Urban Pediatric Primary Care Clinics

Internet, smartphones, and online social media offer new platforms for health promotion and disease management. Few studies have evaluated the use of digital technology among families receiving care in an urban pediatric primary care setting.

Caregivers in an urban pediatric primary care setting have access to and frequently use the Internet, smartphones, and online social media. These technologies may help reach a traditionally hard-to-reach population. (Read the full article)




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The RIVUR Trial: Profile and Baseline Clinical Associations of Children With Vesicoureteral Reflux

The ideal management of children with vesicoureteral reflux (VUR) remains a source of debate. There is little evidence to support many of the current management practices for children with VUR who have had 1 or 2 urinary tract infections.

Baseline associations, including bladder and bowel dysfunction and imaging studies, from the largest randomized, controlled trial conducted to date aimed at assessing the value of antimicrobial prophylaxis in children with urinary tract infection and VUR are presented. (Read the full article)




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All-Terrain Vehicle-Related Nonfatal Injuries Among Young Riders in the United States, 2001-2010

Because children often lack the physical strength, cognitive abilities, and fine motor skills to operate all-terrain vehicles (ATVs) properly, their risk of injury is greater.

During 2001–2010 in the United States, ~361 000 children aged ≤15 years were injured while riding ATVs. The decline in the injury rate during 2005–2010 might be related to the economic recession and decreased sales of new ATVs. (Read the full article)




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Asthma During Pregnancy and Clinical Outcomes in Offspring: A National Cohort Study

Asthma is a common medical complication during pregnancy that is associated with an increased risk of adverse obstetric outcomes.

This study adds knowledge on potential long-term consequences of maternal asthma during pregnancy for offspring health, demonstrating that maternal asthma during pregnancy is linked to a wide spectrum of offspring diseases during childhood. (Read the full article)




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Probiotic Administration in Early Life, Atopy, and Asthma: A Meta-analysis of Clinical Trials

The intestinal microbiome may play a role in immune system maturation, and it has been postulated that early-life probiotic administration may reduce the risk of allergies and asthma in childhood. To date, however, results from clinical trials have been inconsistent.

In this meta-analysis, administration of probiotics in early life may reduce total immunoglobulin E level and protect against atopic sensitization but do not seem to protect against asthma/wheezing. Future trials should carefully select probiotic strains and include longer follow-up. (Read the full article)




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Clinical Characteristics of Pediatric Myasthenia: A Surveillance Study

Pediatric myasthenia encompasses a group of rare and underdiagnosed conditions affecting the neuromuscular junction. Symptoms include fluctuating skeletal muscle weakness, which can progress to respiratory failure if left untreated. The autoimmune form of this condition, in particular, is treatable.

This study describes the incidence, clinical features, diagnostic testing, and treatment trends of pediatric myasthenia in Canada, which have not been previously reported in the literature. (Read the full article)




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Clinical Utility of the Colorado Learning Difficulties Questionnaire

Caregiver behavioral symptom ratings are frequently used to assist in diagnosing childhood behavioral disorders. Although behavioral disorders are highly comorbid with learning disabilities (LDs), little work has examined the utility of caregiver ratings of learning concerns for screening of comorbid LD.

The validity of a time- and cost-efficient caregiver rating of academic concerns (Colorado Learning Difficulties Questionnaire) was examined. The screening measure accurately predicted children without LD, suggesting that the absence of parent-reported difficulties may be adequate to rule out overt LD. (Read the full article)




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Catheter Dwell Time and CLABSIs in Neonates With PICCs: A Multicenter Cohort Study

Peripherally inserted central catheters (PICCs) are essential to deliver life-saving treatment to neonates. Longer PICC dwell times may increase the risk of central line–associated bloodstream infections (CLABSIs) in neonates, but previous studies have yielded inconsistent results, likely due to different study designs, analytic methods, and small sample sizes.

The risk of CLABSIs increases during the 2 weeks after PICC insertion and remains elevated for the catheter duration. These data support daily review of PICC necessity, optimization of catheter maintenance practices, and consideration of novel strategies to prevent CLABSIs. (Read the full article)




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Intravenous Magnesium Sulfate for Vaso-occlusive Episodes in Sickle Cell Disease

Vaso-occlusive episodes (VOEs) are a common complication of sickle cell disease, resulting in morbidity. Magnesium is a vasodilator and has been shown to improve red blood cell hydration. Previous small studies have suggested that treatment with magnesium may decrease VOEs.

Intravenous magnesium sulfate is well tolerated in relatively high doses but had no effect on the length of stay in hospital, pain scores, or cumulative analgesia used in children admitted with painful VOEs in sickle cell disease. (Read the full article)




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Comorbidity Clusters in Autism Spectrum Disorders: An Electronic Health Record Time-Series Analysis

Individuals with autism spectrum disorders have a higher comorbidity burden than the general pediatric population, including higher rates of seizures, psychiatric illness, and gastrointestinal disorders.

Comorbidities do not occur evenly. Our clustering analysis reveals subgroups characterized by seizure, psychiatric disorders, and complex multisystem disorders including auditory and gastrointestinal disorders. Correlations between seizure, psychiatric disorders, and gastrointestinal disorders are validated on a sample from a second hospital. (Read the full article)




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Association Between Pediatric Clinical Trials and Global Burden of Disease

Fewer clinical trials are performed in children compared with other patient populations. It is unknown how well existing pediatric clinical trials are aligned with the needs of children, both in high-income countries and globally.

There is only moderate correlation between clinical trial activity and pediatric burden of disease, with certain conditions substantially underrepresented in the current research portfolio. Our findings provide a benchmark for prioritizing conditions for study, analyzing gaps, and identifying funding priorities. (Read the full article)




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Prospective Evaluation of a Clinical Pathway for Suspected Appendicitis

Although appendicitis is the most common surgical cause of abdominal pain in pediatrics, its diagnosis remains elusive. When evaluated independently, clinical scoring systems and ultrasonography have been shown to have low to moderate sensitivity in the diagnosis of appendicitis.

Our study evaluated the accuracy of a clinical practice guideline combining the Samuel’s pediatric appendicitis score and selective ultrasonography as the primary imaging modality for children with suspected appendicitis. Our clinical pathway demonstrated high sensitivity and specificity. (Read the full article)




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Closed-Loop Automatic Oxygen Control (CLAC) in Preterm Infants: A Randomized Controlled Trial

In preterm infants receiving supplemental oxygen, manual control of the inspired oxygen fraction is often difficult and time consuming, which may increase the risk of complications. We developed a system for automatic oxygen control and proved its efficacy in the past.

A multicenter study adds evidence for the proposed automatic oxygen control system to significantly improve oxygen administration to preterm infants receiving mechanical ventilation or nasal continuous positive airway pressure while reducing workload compared with routine manual oxygen control. (Read the full article)




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Effectiveness of Nebulized Beclomethasone in Preventing Viral Wheezing: An RCT

Viral wheezing is common in preschool-aged children. The efficacy of inhaled steroids in preventing viral wheezing is debated. Despite this debate, nebulized beclomethasone is widely prescribed (particularly in a few countries) to children with upper respiratory tract infections.

Findings from this study confirm that inhaled steroids are not effective in preventing viral wheezing. Moreover, no differences were found in the persistence of symptoms (eg, runny nose, sore throat) or in the parental perception of asthma-like symptom severity. (Read the full article)




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Clinical Utility of PCR for Common Viruses in Acute Respiratory Illness

Quantitative real-time polymerase chain reaction allows sensitive detection of respiratory viruses. The clinical significance of detection of specific viruses is not fully understood, however, and several viruses have been detected in the respiratory tract of asymptomatic children.

Our results indicate that quantitative real-time polymerase chain reaction is limited at distinguishing acute infection from detection in asymptomatic children for rhinovirus, bocavirus, adenovirus, enterovirus, and coronavirus. (Read the full article)




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Clostridium difficile Infection Among Children Across Diverse US Geographic Locations

Little is known about the epidemiology and pathogenicity of Clostridium difficile infection among children, particularly those aged ≤3 years in whom colonization is common and pathogenicity uncertain.

Young children, 1 to 3 years of age, had the highest Clostridium difficile infection incidence. Considering that clinical presentation, outcomes, and disease severity were similar across age groups, C difficile infection in the youngest age group likely represents true disease and not asymptomatic colonization. (Read the full article)




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Collaborative Care Outcomes for Pediatric Behavioral Health Problems: A Cluster Randomized Trial

Integrated or collaborative care intervention models have revealed gains in provider care processes and outcomes in adult, child, and adolescent populations with mental health disorders. However optimistic, conclusions are not definitive due to methodologic limitations and a dearth of studies.

This randomized trial provides further evidence for the efficacy of an on-site intervention (Doctor Office Collaborative Care) coordinated by care managers for children's behavior problems. The findings provide support for integrated behavioral health care using novel provider and caregiver outcomes. (Read the full article)




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Strength Capacity and Cardiometabolic Risk Clustering in Adolescents

Resistance exercise is known to have a robust effect on glycemic control and cardiometabolic health among children and adolescents, even in the absence of weight loss.

Normalized strength capacity is associated with lower cardiometabolic risk clustering in boys and girls, even after adjustment for cardiorespiratory fitness, level of physical activity, and BMI. (Read the full article)




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The Epidemiology and Clinical Features of Kawasaki Disease in Australia

The incidence of Kawasaki disease is increasing in many countries. The only reported Australian incidence (3.4/100 000 <5 years) is almost 20 years old and the current Australian epidemiology and outcomes are unknown.

We analyzed 30 years’ total population hospitalization data from Western Australia. Kawasaki disease incidence increased markedly from 1979 to 2009 and is currently 9.34/100 000 <5 years. The epidemiology and cardiovascular outcomes are similar to other predominantly European-Caucasian populations. (Read the full article)




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Clinical Phenotype of Scabies by Age

Scabies is a frequent cause of consultation and has recently been classified as a neglected disease. The clinical presentation seems to be linked with age, although no specific study has aimed to delineate the clinical spectrum of scabies in infants and children.

Scabies in infants and children has distinct clinical features. This prospective observational study found that infants were more likely to have relapse, nodules, and to present involvement with extremities, face, and scalp, arguing for specific cares in this age group. (Read the full article)




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Motor Vehicle-Pedestrian Collisions and Walking to School: The Role of the Built Environment

Many studies have demonstrated that the built environment is related to both collision risk and walking to school. However, little research examines the influence of the built environment on the relationship between walking to school and pedestrian collision risk.

Increased walking was not associated with increased pedestrian collision once the effects of the built environment and socioeconomic status were modeled. Safety was related primarily to the built environment and specifically features related to road crossing. (Read the full article)




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Academic Achievement of Children and Adolescents With Oral Clefts

Previous studies that reported learning deficits among children with oral clefts mostly used small, clinic-based samples prone to ascertainment bias. No previous studies in the United States have used a population-based sample and direct testing of academic achievement.

Using a large population-based sample from the United States and standardized school tests for achievement, we found that children with oral clefts scored significantly lower than their classmates on all evaluated domains of achievement and had higher rates of learning disability. (Read the full article)




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Emergency Department and Urgent Care for Children Excluded From Child Care

Previous studies have revealed that children in child care are frequently ill with mild illness and are unnecessarily excluded from child care at high rates.

Parent race/ethnicity, single parents, and work-related concerns are associated with increased emergent/urgent care use for a sick child excluded from child care, even for mild illnesses. (Read the full article)




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Neonatal Outcome Following Cord Clamping After Onset of Spontaneous Respiration

Delaying cord clamping beyond 30 to 60 seconds after birth seems beneficial for all infants due to blood transfusion from placenta. Experimental data have demonstrated that ventilation implemented before cord clamping improved cardiovascular stability by increasing pulmonary blood flow.

Healthy self-breathing neonates in a low-resource setting are more likely to die if cord clamping occurs before or immediately after onset of spontaneous respirations. The risk of death/admission decreases by 20% for every 10-second delay in clamping after breathing. (Read the full article)




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A Clinical Prediction Rule for the Severity of Congenital Diaphragmatic Hernias in Newborns

Predicting high-risk populations in congenital diaphragmatic hernia (CDH) can help target care strategies. Prediction rules for infants with CDH often lack validation, are aimed at a prenatal population, and are of limited generalizability. We cannot currently discriminate the highest risk neonates during the crucial period shortly after birth.

This clinical prediction rule was developed and validated on an international database. It discriminates patients and high, intermediate, and low risk of mortality; is easy to apply; and is generalizable to most infants with CDH. (Read the full article)




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Impact of Pediatric Exclusivity on Drug Labeling and Demonstrations of Efficacy

Most therapeutic products used in children have not been studied in that population. There is a need for special incentives and market protection (pediatric exclusivity) to compensate drug sponsors for studying these products in children.

Of 189 products studied under pediatric exclusivity, 173 (92%) received new labeling information. Pediatric efficacy was not established for 78 (42%), including 81% of oncology drugs. Probability of demonstrating efficacy was related to therapeutic area and year exclusivity was granted. (Read the full article)




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The Timing of Cord Clamping and Oxidative Stress in Term Newborns

Clamping and cutting of the umbilical cord at birth is the most prevalent of all operations; however, the optimal timing of cord clamping is still a controversial issue, with different timings offering advantages and disadvantages.

Our findings suggest a protective effect of late cord clamping, increasing the antioxidant capacity and decreasing the inflammatory-mediated effects induced during delivery of term neonates. (Read the full article)




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Herpes PCR Testing and Empiric Acyclovir Use Beyond the Neonatal Period

Herpes encephalitis outside the neonatal period is typically severe and recognizable to clinicians. Excessive testing for herpes encephalitis is associated with increased medical costs and hospital length of stay, and risks patient harm.

Herpes testing and empirical acyclovir treatment in older and less unwell patients has been increasing in US pediatric hospitals over the past decade, which may reflect a more fundamental problem in current approaches to clinical decision-making. (Read the full article)