Comorbidity of Migraine and Epilepsy in Pediatrics: A Review.

Migraine and epilepsy are classified as chronic paroxysmal neurologic disorders sharing many clinical features, as well as possible treatment options. This review highlights the similarities between migraine and epilepsy in pediatrics, focusing on epidemiologic, pathophysiological, genetic, clinical, and pharmacologic aspects. Despite the fact that several syndromes share symptoms of both migraine and epilepsy, further research is needed to clarify the pathophysiological and genetic basis of their comorbidity.

Breast-feeding, Leptin:Adiponectin Ratio, and Metabolic Dysfunction in Adolescents with Obesity.

Objectives: Increased adiposity increases leptin and decreases adiponectin concentrations, resulting in an increased leptin:adiponectin ratio (LAR). In adults, components of the metabolic syndrome and other cardiometabolic risk factors, what we classify here as "metabolic dysfunction," are associated with both a high LAR and a history of being breast-fed. The relation among breast-feeding, LAR, and degree of metabolic dysfunction in obese youth is unknown.

Use of Fentanyl in Adolescents with Clinically Severe Obesity Undergoing Bariatric Surgery: A Pilot Study.

Background: The number of obese pediatric patients requiring anesthesia is rapidly increasing. Although fentanyl is a commonly used narcotic during surgery, there are no pharmacokinetic (PK) data available for optimal dosing of fentanyl in adolescents with clinically severe obesity.

Materials And Methods: An institutional review board-approved exploratory pilot study was conducted in six adolescents aged 14-19 years undergoing bariatric surgery.

Waiting 2 minutes after sucrose administration-unnecessary?

Background: Worldwide, oral sucrose is standard of care in many neonatal intensive care units to relieve procedural pain in neonates. This study aims to determine if time interval between sucrose administration and heelstick correlates with pain scores.

Methods: Neonates were prospectively studied with variable time intervals and assessed with the Premature Infant Pain Profile-Revised (PIPP-R).

How to optimise drug study design: pharmacokinetics and pharmacodynamics studies introduced to paediatricians.

Objectives: In children, there is often lack of sufficient information concerning the pharmacokinetics (PK) and pharmacodynamics (PD) of a study drug to support dose selection and effective evaluation of efficacy in a randomised clinical trial (RCT). Therefore, one should consider the relevance of relatively small PKPD studies, which can provide the appropriate data to optimise the design of an RCT.

Methods: Based on the experience of experts collaborating in the EU-funded Global Research in Paediatrics consortium, we aimed to inform clinician-scientists working with children on the design of investigator-initiated PKPD studies.

Multiple Sclerosis in Pediatrics: Current Concepts and Treatment Options.

Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory, demyelinating disease of the central nervous system. MS is increasingly recognized in the pediatric population, and it is usually diagnosed around 15 years of age. The exact etiology of MS is still not known, although autoimmune, genetic, and environmental factors play important roles in its development, making it a multifactorial disease.

Different Vancomycin Immunoassays Contribute to the Variability in Vancomycin Trough Measurements in Neonates.

Substantial interassay variability (up to 20%) has been described for vancomycin immunoassays in adults, but the impact of neonatal matrix is difficult to quantify because of blood volume constraints in neonates. However, we provide circumstantial evidence for a similar extent of variability. Using the same vancomycin dosing regimens and confirming similarity in clinical characteristics, vancomycin trough concentrations measured by PETINIA (2011-2012, n = 400) were 20% lower and the mean difference was 1.

The amikacin research program: a stepwise approach to validate dosing regimens in neonates.

For safe and effective use of antibacterial agents in neonates, specific knowledge on the pharmacokinetics (PK) and its covariates is needed. This necessitates a stepwise approach, including prospective validation. Areas covered: We describe our approach throughout almost two decades to improve amikacin exposure in neonates.

Genetic Predictors of Susceptibility to Dermatophytoses.

Countless observational studies conducted over the last century reveal that dermatophytes infect humans of every age, race, gender, and socioeconomic status with strikingly high rates. The curious disparity in dermatophyte infection patterns observed within and between populations has led countless investigators to explore whether genetics underlie a susceptibility to, or confer protection against, dermatophyte infections. This paper examines the data that offer a link between genetics and dermatophytoses and discusses the underlying mechanisms that support these observations.

Causes and Consequences of Variability in Drug Transporter Activity in Pediatric Drug Therapy.

Drug transporters play a key role in mediating the uptake of endo- and exogenous substances into cells as well as their efflux. Therefore, variability in drug transporter activity can influence pharmaco- and toxicokinetics and be a determinant of drug safety and efficacy. In children, particularly in neonates and young infants, the contribution of tissue-specific drug transporters to drug absorption, distribution, and excretion may differ from that in adults.

Clinical pharmacology of analgosedatives in neonates: ways to improve their safe and effective use.

Objectives: To propose approaches tailored to the specific needs of neonates, such as structured product development programmes, with the ultimate goal to improve the safe and effective use of analgosedatives in these fragile patients.

Key Findings: The feasibility and relevance of a structured product development programme in neonates (optimal study design based on preliminary data; model development; internal, external and prospective evaluation; an individualized dosing regimen; long-term safety; pharmacogenetics) are illustrated for the use of morphine. Based on changes in clinical practices, similar development plans are in progress for short-acting analgosedatives such as propofol, but are in need of tailored pharmacodynamic tools to assess and quantify effects.

Characterizing and Forecasting Individual Weight Changes in Term Neonates.

Objectives: To develop a mathematical, semimechanistic model characterizing physiological weight changes in term neonates, identify and quantify key maternal and neonatal factors influencing weight changes, and provide an online tool to forecast individual weight changes during the first week of life.

Study Design: Longitudinal weight data from 1335 healthy term neonates exclusively breastfed up to 1 week of life were available. A semimechanistic model was developed to characterize weight changes applying nonlinear mixed-effects modeling.

Pediatric Clinical Pharmacology of Voriconazole: Role of Pharmacokinetic/Pharmacodynamic Modeling in Pharmacotherapy.

Voriconazole is a potent antifungal agent used for the treatment of invasive fungal infections caused by Aspergillus and Candida species in adult and pediatric patients. Voriconazole has a narrow therapeutic index and a large intra- and inter-individual pharmacokinetics (PK) variability. Several factors including non-linear PK, age, body weight, cytochrome P450 2C19 genotype, concomitant drugs, liver function, and food are responsible for the large variability in voriconazole PK.

Quantitative clinical pharmacology practice for optimal use of antibiotics during the neonatal period.

Introduction: For safe and effective neonatal antibiotic therapy, knowledge of the pharmacokinetic parameters of antibacterial agents in neonates is a prerequisite. Fast maturational changes during the neonatal period influence pharmacokinetic and pharmacodynamic parameters and their variability. Consequently, the need for applying quantitative clinical pharmacology and determining optimal drug dosing regimens in neonates has become increasingly recognized.

Development of Extemporaneously Compounded Aripiprazole Oral Suspensions for Use in Children.

The purpose of this study was to develop extemporaneously compounded oral liquid formulations of aripiprazole for use in pediatric patients and those patients unable to swallow the solid oral dosage forms. Aripiprazole tablets(30 mg) were ground to a fine powder and suspended at a concentration of 1.0 mg/mL in either a 1:1 blend of Ora-Plus and Ora-Sweet, or 1% methylcellulose and Simple Syrup NF.

Towards Rational Dosing Algorithms for Vancomycin in Neonates and Infants Based on Population Pharmacokinetic Modeling.

Because of the recent awareness that vancomycin doses should aim to meet a target area under the concentration-time curve (AUC) instead of trough concentrations, more aggressive dosing regimens are warranted also in the pediatric population. In this study, both neonatal and pediatric pharmacokinetic models for vancomycin were externally evaluated and subsequently used to derive model-based dosing algorithms for neonates, infants, and children. For the external validation, predictions from previously published pharmacokinetic models were compared to new data.

Possible effects of repeated exposure to ibuprofen and acetaminophen on the intestinal immune response in young infants.

There has been an exponential increase in the frequency of immune deviations in young children. Consequently, research investigating environmental causes for this increase has become a Public Health priority. We have summarized the experimental observations and epidemiological data that could link repeated acetaminophen and ibuprofen exposure in early infancy to this increase.

Age, Sexual Dimorphism, and Disease Associations in the Developing Human Fetal Lung Transcriptome.

The fetal origins of disease hypothesis suggests that variations in the course of prenatal lung development may affect life-long pulmonary function growth, decline, and pathobiology. Many studies support the existence of differences in the developing lung trajectory in males and females, and sex-specific differences in the prevalence of chronic lung diseases, such as asthma and bronchopulmonary dysplasia. The objectives of this study were to investigate the early developing fetal lung for transcriptomic correlates of postconception age (maturity) and sex, and their associations with chronic lung diseases.