Clinical Pharmacology of Frequently Used Intravenous Drugs During Bariatric Surgery in Adolescents.

Obesity represents one of the most important public health issues according to the World Health Organization. Additionally, in a recent National Health and Nutrition Survey of 2011-2012, approximately 17 % of children and adolescents in the United States were considered obese. The obesity rate is higher within the adolescent age group as compared to preschool children.

Availability of Oral Formulations Labeled for Use in Young Children in Serbia, Germany and the USA.

Background: The paucity of marketed drug products that have been adequately studied in infants and children and subsequently, licensed (or labeled) for pediatric use has caused abundant use of off-label and unauthorized products in this patient population. In those instances where insufficient pharmacologic or therapeutic information exists for children, the potential for off-label use of medicines to result in therapeutic misadventure does as well. In the USA, a series of regulatory measures have been introduced since 1997 which have increased both the number and scope of pediatric drug trials and also, fostered the development of ageappropriate drug formulations by pharmaceutical companies.

Neonatal Formulations: The Need for a Tailored, Knowledge Driven Approach.

To attain effective and safe pharmacotherapy in neonates, caregivers have to consider both the clinical characteristics of the newborn and the pharmacokinetic estimates of a given compound during prescription and administration. Overall, clearance in neonates is low when compared to other pediatric subpopulations. Despite this overall low clearance, there is already extensive between individual variability in clearance in early life.

Dosing Guidelines of Aminoglycosides in Neonates: A Balance Between Physiology and Feasibility.

Once daily dosing of aminoglycosides has been introduced and validated in non-neonatal patient cohorts. This is because aminoglycosides display peak concentration dependent bacterial killing, have a postantibiotic effect and adaptive resistance. In addition, this strategy reduces toxicity.

The Impact of Hypothermia on the Pharmacokinetics of Drugs Used in Neonates and Young Infants.

Therapeutic hypothermia (HT) is frequently used in neonates with hypoxic-ischemic encephalopathy and young infants during cardiopulmonary bypass (CPB). Hypothermia and CPB result in physiological changes contributing to pharmacokinetic (PK) and pharmacodynamic (PD) changes. Changes in the absorption, the volume of distribution (Vd) and the total body clearance (CL) of drugs used during hypothermia and CPB might lead to the interindividual PK variability resulting in either insufficient or toxic plasma concentrations and have an impact on the biodisposition and action of drugs.

How to use vancomycin optimally in neonates: remaining questions.

In neonates, vancomycin, a narrow-spectrum antibiotic, is the first choice of treatment of late-onset sepsis predominantly caused by Gram-positive bacteria (coagulase-negative staphylococci and enterococci). Although it has been used for >50 years, prescribing the right dose and dosing regimen remains a challenge in neonatal intensive care units for many reasons including high pharmacokinetic variability, increase in the minimal inhibition concentration against staphylococci, lack of consensus on dosing regimen and way of administration (continuous or intermittent), duration of treatment, use of therapeutic drug monitoring, limited data on short- and long-term toxicity, risk of mutant selection and errors of administration linked to concentrated formulations. This article highlights and discusses future research directions, with specific attention given to dosing optimization of vancomycin, including the advantages of modeling and simulation approaches.

The use of urinary and kidney SILAM proteomics to monitor kidney response to high dose morpholino oligonucleotides in the mdx mouse.

Phosphorodiamidate morpholino oligonucleotides (PMO) are used as a promising exon-skipping gene therapy for Duchenne Muscular Dystrophy (DMD). One potential complication of high dose PMO therapy is its transient accumulation in the kidneys. Therefore new urinary biomarkers are needed to monitor this treatment.

Population Pharmacokinetics of Intravenous Paracetamol (Acetaminophen) in Preterm and Term Neonates: Model Development and External Evaluation.

Objectives: The aims of this study were to develop a population pharmacokinetic model for intravenous paracetamol in preterm and term neonates and to assess the generalizability of the model by testing its predictive performance in an external dataset.

Methods: Nonlinear mixed-effects models were constructed from paracetamol concentration-time data in NONMEM 7.2.

Limited effects of intravenous paracetamol on patent ductus arteriosus in very low birth weight infants with contraindications for ibuprofen or after ibuprofen failure.

Unlabelled: Finding the optimal pharmacological treatment of a patent ductus arteriosus (PDA) in preterm neonates remains challenging. There is a growing interest in paracetamol as a new drug for PDA closure. In this prospective observational cohort study, we evaluated the effectiveness of intravenous paracetamol in closing a PDA in very low birth weight infants with a hemodynamically significant PDA who either did not respond to ibuprofen or had a contraindication for ibuprofen.

Novel model-based dosing guidelines for gentamicin and tobramycin in preterm and term neonates.

Objectives: In the heterogeneous group of preterm and term neonates, gentamicin and tobramycin are mainly dosed according to empirical guidelines, after which therapeutic drug monitoring and subsequent dose adaptation are applied. In view of the variety of neonatal guidelines available, the purpose of this study was to evaluate target concentration attainment of these guidelines, and to propose a new model-based dosing guideline for these drugs in neonates.

Methods: Demographic characteristics of 1854 neonates (birth weight 390-5200 g, post-natal age 0-27 days) were extracted from earlier studies and sampled to obtain a test dataset of 5000 virtual patients.

Use of Enoxaparin in Obese Adolescents During Bariatric Surgery--a Pilot Study.

Background: Obese patients have a higher risk of venous thromboembolism when immobilized due to surgery. The objective of this study was to assess anti-factor Xa activity in adolescent bariatric surgical patients receiving prophylactic enoxaparin.

Methods: Four morbidly obese adolescents undergoing laparoscopic sleeve gastrectomy were enrolled.

Safety of milrinone use in neonatal intensive care units.

Background: Milrinone use in the neonatal intensive care unit has increased over the last 10 years despite a paucity of published safety data in infants. We sought to determine the safety of milrinone therapy among infants in the neonatal intensive care unit.

Methods: We conducted a retrospective data analysis, identifying all infants who were exposed to milrinone and discharged from 322 neonatal intensive care units managed by the Pediatrix Medical Group from 1997-2010.

Cystatin C in newborns: a promising renal biomarker in search for standardization and validation.

Objective: Neonatologists still commonly use creatinine as a proxy for renal clearance, despite issues related to neonatal (patho)physiology and methodology (assay variability). Cystatin C (CysC) has been suggested to be a more reliable biomarker, but assay related differences have also been reported in children and adults. We are unaware of any review on the assay related impact on CysC reference values in newborns.

The impact of pediatric labeling changes on prescribing patterns of cough and cold medications.

Objective: To evaluate the impact of initiatives created by the pharmaceutical industry and the Food and Drug Administration to limit the use of over-the-counter (OTC) cough and cold medications (CCMs) in young children in emergency departments (EDs) and ambulatory clinics.

Study Design: Analysis of the National Hospital Ambulatory Medical Care Survey and National Ambulatory Medical Care Survey was performed comparing 2005-2006 and 2009-2010 in children aged ≤ 12 years with a reason for visit consistent with cough or cold-related symptoms. Data were stratified by age (<2 years, 2-6 years, and 6-12 years).

Trends in opioid analgesic use for headaches in US emergency departments.

Objective: Although not recommended as first line therapy by consensus guidelines, opioid analgesics are commonly used to treat headaches. This study evaluates trends in opioid use for headaches in US emergency departments (EDs).

Methods: We performed a retrospective review of the National Hospital Ambulatory Medical Care Survey, 2001 through 2010.

Critical drug shortages: implications for emergency medicine.

Prescription drug shortages have become increasingly common and more severe over the past decade. In addition, reported shortages are longer in duration and have had a greater effect on patient care. Some of the causes of current drug shortages are multifactorial, including the consolidation of drug manufacturers, quality problems at production plants that restrict the supply of drugs, and a lack of financial incentives for manufacturers to produce certain products, particularly generic medications.

Clinical pharmacology in neonates: small size, huge variability.

Drug therapy is a powerful tool for improving neonatal outcome. Despite this, neonatologists still routinely prescribe off-label compounds developed for adults and extrapolate doses from those used for children or adults. Knowledge integration through pharmacokinetic modeling is a method that could improve the current situation.

The impact of race on analgesia use among pediatric emergency department patients.

We studied the effect of race on analgesia use in potentially pain-related pediatric emergency department visits using the National Hospital Ambulatory Medical Care Survey (2005-2010). There were independent patient- and hospital-level racial disparities when it came to the type of analgesia used, suggesting black children are treated differently even within hospitals with high numbers of black patients.