Evaluation of Different Methods Used to Calculate Ideal Body Weight in the Pediatric Population.

OBJECTIVES: Accurate determination of ideal body weight (IBW) in pediatric patients is important for the proper dosing of many medications and the classification of nutritional status. There is no consensus on the best method to calculate IBW. The purpose of this study is to evaluate and compare 7 different methods used to calculate IBW in the pediatric population. METHODS: This was a retrospective observational study. All subjects were pediatric inpatients at a 536-bed community teaching hospital between January 1, 2016, and June 30, 2017. Subjects were divided into 2 cohorts: cohort 1 was aged 12 months and 0 day to 35 months and 30 days, and cohort 2 was aged 36 months and 0 day to 17 years and 364 days. The McLaren method was used as the reference to compare with 6 other methods: Moore method, Devine method, American Dietetic Association (ADA) method, body mass index (BMI) method, Traub equation, and simplified Traub equation. RESULTS: For cohort 1 (n = 347), the Moore method was not statistically different from the McLaren method with a mean difference of -0.07 kg (95% CI: -0.14 to 0.01, p = 0.07). For cohort 2 (n = 1095), the BMI method was not statistically different from the McLaren method with a mean difference of 0.17 kg (95% CI: -0.07 to 0.40, p = 0.17). CONCLUSIONS: In both cohorts, the majority of methods used to calculate IBW in pediatric patients leads to statistically different results when compared with the McLaren method. For certain methods, these differences become pronounced at high and low height percentiles and in older age groups.

A Review on the Use of Cystic Fibrosis Transmembrane Conductance Regulator Gene Modulators in Pediatric Patients.

The literature surrounding the use of cystic fibrosis transmembrane conductance regulator-targeted pharmacotherapies in pediatric patients continues to evolve. These therapies represent a departure from symptom management and infection prevention, which have been the mainstay of cystic fibrosis management in pediatrics, to targeting the genetic defect present within these patients. This article reviews the clinical studies evaluating the safety and efficacy of ivacaftor, ivacaftor/lumacaftor, and ivacaftor/tezacaftor. These medications were initially studied in adults and adolescents but have begun to be studied in younger populations. Further investigation into the use of these drugs with different CFTR mutations and in younger age groups will continue to expand the number of patients who can benefit from these therapies.

The Use of Codeine and Tramadol in the Pediatric Population-What is the Verdict Now?

Codeine and tramadol are opioid analgesics approved for the management of pain in the United States. Both agents are metabolized in the liver to active compounds via the cytochrome P450 2D6 enzyme. Case reports of pediatric patients with overactive CYP2D6 enzymes have been reported. These ultra-rapid metabolizers experience an increase in the production of active metabolites of codeine and tramadol, which can lead to oversedation, respiratory depression, and death. In 2017, the U.S. Food and Drug Administration updated their warnings regarding codeine and tramadol use in the pediatric population, making their use contraindicated in patients under the age of 12 years.

Treatment of pediatric Clostridium difficile infection: a review on treatment efficacy and economic value.

The incidence of Clostridium difficile infection (CDI) in pediatric patients continues to rise. Most of the pediatric recommendations for CDI treatment are extrapolated from the literature and guidelines for adults. The American Academy of Pediatrics recommends oral metronidazole as the first-line treatment option for an initial CDI and the first recurrence if they are mild to moderate in severity. Oral vancomycin is recommended to be used for severe CDI and the second recurrent infection. Additional pulsed regimen of oral vancomycin, which is tapered, may increase efficacy in refractory patients. However, there is lack of large studies evaluating the use of fidaxomicin in pediatrics to know whether it could be a safe and effective treatment option for difficult-to-treat patients. Fidaxomicin is associated with higher total drug costs compared to metronidazole and vancomycin, but the literature supports its use due to a lower rate of CDI recurrence, which may result in cost savings. Further studies are warranted to evaluate the use of fidaxomicin in patients <18 years old and to understand its role in the standard of care for pediatric patients with CDI.

Evaluation of the Efficacy of a Onetime Injectable Dexamethasone Administered Orally in the Pediatric Emergency Department for Asthma Exacerbation.

OBJECTIVE: This study assessed the efficacy of injectable dexamethasone administered orally in pediatric patients who presented to the emergency department with asthma exacerbation. METHODS: This was a retrospective study of patients 0 to 18 years of age who presented to and who were directly discharged from the emergency department at Moses H. Cone Memorial Hospital between September 1, 2012, and September 30, 2015, for the diagnosis of asthma or asthma exacerbation. Patients had to receive a onetime dose of injectable dexamethasone orally prior to discharge. Patients were followed for a 30-day period to identify the number of asthma relapses. RESULTS: Ninety-nine patients were included in this study. The average weight-based dose ± SD of dexamethasone was 0.35 ± 0.18 mg/kg (range, 0.08-0.62 mg/kg) and the actual dose ± SD was 10.58 ± 1.92 mg (range, 5-16 mg). Over a 30-day period, 6 patients (6%) had one repeated emergency department visit, 6 patients (6%) were admitted to the hospital, and 3 patients (3%) presented to an outpatient clinic for asthma-related symptoms. CONCLUSIONS: Injectable dexamethasone administered orally may be an efficacious treatment for asthma exacerbation in pediatric patients. A randomized control trial comparing injectable dexamethasone administered orally to other dexamethasone formulations/routes of administration should be performed to adequately assess the bioequivalence and effectiveness of the former formulation.

Primary Immunization of Human Papillomavirus Vaccine in the Pediatric Population: What Is the Verdict Now?

The safety and efficacy of a 2-dose series for the human papillomavirus vaccines rather than a 3-dose series in older children has not been well defined. This article reviews the literature summarizing the use of all 3 HPV vaccines (2vHPV, 4vHPV, 9vHPV) as a 2-dose series for females and 4vHPV and 9vHPV for males younger than 15 years. Six prospective trials evaluating immunogenicity of a 2-dose series of 2vHPV and/or 4vHPV, as well as an ongoing prospective clinical trial for 9vHPV, are discussed. The 2-dose series with Gardasil 9® in both males and females ages 9 to 14 years appears to be the most widely accepted recommendation. The exact time schedule between the 2 vaccines varies among studies, but it seems that they should be separated by 6 to 12 months. Federal and world-wide organizations' (ie, Centers for Disease Control and Prevention, Food and Drug Administration, and World Health Organization) opinions and recommendations on the appropriate scheduling of the vaccines are also highlighted.

Current Clinical Trials on the Use of Ceftaroline in the Pediatric Population.

The rate of antibiotic resistance in children continues to rise requiring the use of new antibiotics. Ceftaroline fosamil, a newer-generation cephalosporin, was recently approved for the treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia in children aged >2 months. Ceftaroline provides coverage against staphylococcal and streptococcal infections, including methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae. Pediatric dosing differs from adult dosing, but it maintains a similar pharmacokinetic profile and offers similar efficacy in terms of time above the minimum inhibitory concentration as compared to the adult population. The clinical safety and efficacy of this antibiotic has been assessed in three pediatric clinical trials that led to its approval by the US Food and Drug Administration, and each trial is described within this review. This article will also discuss the ongoing trials assessing the possibility of expanding the indications of this antibiotic to late-onset sepsis, meningitis and osteomyelitis in the pediatric population.

Transitioning antimicrobials from intravenous to oral in pediatric acute uncomplicated osteomyelitis.

Osteomyelitis is a bone infection that requires prolonged antibiotic treatment and potential surgical intervention. If left untreated, acute osteomyelitis can lead to chronic osteomyelitis and overwhelming sepsis. Early treatment is necessary to prevent complications, and the standard of care is progressing to a shorter duration of intravenous (IV) antibiotics and transitioning to oral therapy for the rest of the treatment course. We systematically reviewed the current literature on pediatric patients with acute osteomyelitis to determine when and how to transition to oral antibiotics from a short IV course. Studies have shown that switching to oral after a short course (i.e., 3-7 d) of IV therapy has similar cure rates to continuing long-term IV therapy. Prolonged IV use is also associated with increased risk of complications. Parameters that help guide clinicians on making the switch include a downward trend in fever, improvement in local tenderness, and a normalization in C-reactive protein concentration. Based on the available literature, we recommend transitioning antibiotics to oral after 3-7 d of IV therapy for pediatric patients (except neonates) with acute uncomplicated osteomyelitis if there are signs of clinical improvement, and such regimen should be continued for a total antibiotic duration of four to six weeks.

Attention Deficit Hyperactive Disorder and Occurrence of Tic Disorders in Children and Adolescents-What is the Verdict.

The United States Food and Drug Administration currently states that the use of stimulants in patients with tic disorders and/or family history of tic disorders including Tourette's syndrome is contraindicated. Patients with attention deficit hyperactivity disorder (ADHD), however, are at increased risk of tics regardless of stimulants use. After evaluating the most recent literature on the incidence of tic disorders in pediatric patients treated with stimulants for ADHD, it is reasonable to say that the incidence of tics and the severity of tics are not increased by the use of these medications. For patients with pre-existing tic disorders, the usual recommended dosing of stimulants should be used because supratherapeutic doses of this class of medications, specifically dextroamphetamine, have shown to exacerbate tic disorders.

Hypersensitivity Reaction to Insulin Glargine and Insulin Detemir in a Pediatric Patient: A Case Report.

Allergy to human insulin or its analogs is rare, but it is still a significant issue in current diabetes care. Allergic reactions can range from localized injection site reactions to generalized anaphylaxis, and they can be caused by excipients or the insulin molecules themselves. We presented a case of a 14-year-old male patient with generalized allergic reactions to insulin glargine and insulin detemir. The patient was successfully managed by being switched to a continuous subcutaneous insulin infusion with insulin aspart. Allergic reactions to insulin detemir and insulin glargine have both been well described, with insulin detemir allergy appearing to be more common. There are several potential mechanisms for insulin allergy, and immunologic characteristics vary among different insulin analogs. After confirming insulin allergy in practice, management involves treating symptoms and switching insulin preparations. This is the first documented case of allergies to both insulin glargine and insulin detemir in a pediatric patient. Exact mechanism of insulin allergy is unknown, and management strategies must be individualized for each patient.

Current Clinical Trials on the Use of Direct Oral Anticoagulants in the Pediatric Population.

Common treatment options for deep vein thrombosis and venous thromboembolism in the pediatric population include unfractionated heparin, low molecular weight heparin, and warfarin. Other alternatives are bivalirudin, argatroban, and fondaparinux. Warfarin is the only approved oral option, but an oral agent without frequent monitoring would be optimal for pediatric patients. Thus, there is an increasing need for new anticoagulation options in this population. None of the current direct oral anticoagulants have FDA-approved indications and dosing in children. The two classes of DOACs and the drugs they are comprised of are factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) and direct thrombin inhibitor (dabigatran). Off-label usage of these agents is largely based on adult doses. By far, rivaroxaban and dabigatran have the most published data and ongoing trials in pediatric patients compared to edoxaban and apixaban. After evaluating the current literature available on these agents, it is, however, still too early to make any definitive recommendations on their usage in this special population.

Overview of Pharmacological Treatment Options for Pediatric Patients with Refractory Kawasaki Disease.

Kawasaki disease is an autoimmune disease found predominantly in children under the age of 5 years. Its incidence is higher in those who live in Asian countries or are of Asian descent. Kawasaki disease is characterized as an acute inflammation of the vasculature bed affecting mainly the skin, eyes, lymph nodes, and mucosal layers. Although the disease is usually self-limiting, patients may develop cardiac abnormalities that can lead to death. The exact cause of the disease is unknown; however, researchers hypothesize that an infectious agent is responsible for causing Kawasaki disease. Initial treatment options with intravenous immune globulin and aspirin are sufficient to cure most patients who acquire this disease. Unfortunately, in up to one-quarter of patients, the disease will be refractory to initial therapy and will require further management with corticosteroid, immunomodulatory, or cytotoxic agents. The lack of randomized, controlled trials makes treatment of refractory disease difficult to manage. Until larger randomized, controlled trials are published to give more guidance on therapy for this stage of disease, clinicians should use the data available from observational studies and case reports in conjunction with their clinical expertise to make treatment decisions.

Revisiting the safety of over-the-counter cough and cold medications in the pediatric population.

Increased reports of serious adverse events in young children have led to numerous investigations of its therapeutic role in the pediatric population. A review of the literature has shown limited support of its use in young children, with the majority of randomized controlled trials showing no difference in endpoints when compared to placebo. Because of the recent recommended changes to pediatric cough and cold medication use, studies have suggested a decline in ingestion misuses, health care referrals, and reports of adverse events. While these patterns of use are reassuring, clinicians should continue to educate and provide caregivers guidance in managing cough and cold symptoms. Although a tremendous improvement in frequency of therapeutic error ingestions in children younger than 2 years was shown in these studies, the same magnitude of improvement was not seen in children 2 to 12 years. Therefore, future research is necessary to investigate its role in children younger than 12 years.

Tramadol use in pediatric sickle cell disease patients with vaso-occlusive crisis.

AIM: To evaluate whether the addition of scheduled oral tramadol to intravenous morphine and intravenous ketorolac reduces morphine requirements. METHODS: This single-centered, Institutional Review Board-approved, retrospective study at Moses Cone Memorial Hospital included pediatric patients who were ≥ 2 years old with vaso-occlusive crisis (VOC) caused by sickle cell disease (SCD), were on morphine patient-controlled analgesia (PCA), and had scheduled oral tramadol added to their standard pain regimen. The study population was admitted between March 2008 and March 2011. The data was collected from electronic records and included age, weight, morphine use, tramadol use, hemoglobin, pain scores, number of days on PCA, length of hospital stay, respiratory rate, and polyethylene glycol use. Thirty patients were analyzed as independent admissions and seven patients as paired admissions. RESULTS: Eighteen pediatric SCD patients with VOC received morphine PCA and intravenous ketorolac and twelve patients received morphine PCA and intravenous ketorolac and scheduled oral tramadol. Baseline characteristics were similar between both groups with the exception of the average weight, which was greater in the tramadol group than in the morphine group. The average morphine requirements in patients with and without the use of tramadol were similar, both for the independent admissions [0.58 mg/kg per day vs 0.65 mg/kg per day (P = 0.31)] and the paired admissions [0.71 mg/kg per day vs 0.77 mg/kg per day (P = 0.5)]. The daily polyethylene glycol requirement was less in the tramadol group for both the independent [0.5 g/kg per day vs 0.6 g/kg per day (P = 0.64)] and paired admissions analyses [and 0.41 g/kg per day vs 0.55 g/kg per day (P = 0.67)]. CONCLUSION: The addition of scheduled tramadol in patients receiving concomitant morphine and ketorolac demonstrates a trend toward decreased morphine and polyethylene glycol use.

A review on vitamin d deficiency treatment in pediatric patients.

Vitamin D is essential for calcium absorption and for maintaining bone health in the pediatric population. Vitamin D deficiency may develop from nutritional deficiencies, malabsorption, enzyme-inducing medications, and many other etiologies. It may present as hypocalcemia before bone demineralization at periods of increased growth velocity (infancy and adolescence) because the increased calcium demand of the body cannot be met. In children, inadequate concentrations of vitamin D may cause rickets and/or symptomatic hypocalcemia, such as seizures or tetany. In this review, we will discuss the pharmacology behind vitamin D supplementation, laboratory assessments of vitamin D status, current literature concerning vitamin D supplementation, and various supplementation options for the treatment of vitamin D deficiency in the pediatric population.

The use of ketogenic diet in pediatric patients with epilepsy.

A ketogenic diet is a nonpharmacologic treatment strategy to control refractory epilepsy in children. Although this diet has been used successfully to reduce seizures since the 1920s, the anticonvulsant mechanism of ketosis remains unknown. The initiation of the diet requires an average four-day hospitalization to achieve ketosis in the patient as well as to provide thorough education on diet maintenance for both the patient and the caregivers. A ketogenic diet, consisting of low carbohydrate and high fat intake, leaves little room for additional carbohydrates supplied by medications. Patients on ketogenic diets who exceed their daily carbohydrate limit have the risk of seizure relapse, necessitating hospital readmission to repeat the diet initiation process. These patients are at a high risk for diversion from the diet. Patients admitted to the hospital setting are often initiated on multiple medications, and many hospital systems are not equipped with appropriate monitoring systems to prevent clinicians from introducing medications with high carbohydrate contents. Pharmacists have the resources and the expertise to help identify and prevent the initiation of medications with high carbohydrate content in patients on ketogenic diets.

Use of anticoagulation therapy for jugular vein thrombus in pediatric patients with Lemierre's syndrome.

BACKGROUND: Lemierre's syndrome is a rare condition involving septic thrombophlebitis of the internal jugular vein secondary to an acute oropharyngeal infection. The low incidence and prevalence of Lemierre's syndrome contribute to the many controversies pertaining to its therapeutic management, one of which is the use of anticoagulation for associated internal jugular vein thrombus. CASE DESCRIPTION: A previously healthy 5-year-old male admitted with left internal jugular vein thrombosis associated with Lemierre's syndrome was placed on appropriate antibiotics and anticoagulation therapy with enoxaparin. 3 weeks post-discharge, patient was found to be in good condition and a magnetic resonance angiography showed persistent occlusion of the left internal jugular vein. CONCLUSION: Anticoagulation therapy for internal jugular vein thrombosis associated with Lemierre's syndrome remains a controversy. In the absence of any contraindication or presumed risk, anticoagulation therapy should be considered in high risk patients.

First-line disease-modifying therapies in paediatric multiple sclerosis: a comprehensive overview.

Paediatric multiple sclerosis (MS) is defined as the onset of MS before the age of 18 years. Immunomodulatory disease-modifying therapies (i.e. the interferons [IFNs] and glatiramer acetate) are considered first-line treatments in adult patients with MS, but they are largely understudied in the paediatric population. IFNß is a type 1 IFN produced by fibroblasts. The therapeutic effect achieved by IFNß in MS is believed to be the result of a variety of mechanisms, including the inhibition of T-cell proliferation and a shift in cytokine production. There are currently two forms of recombinant IFNß used therapeutically for MS: IFNß-1a and IFNß-1b. Two formulations of IFNß-1a exist, one administered as an intramuscular injection once weekly and the other by subcutaneous injection three times per week. Only one type of IFNß-1b product is on the market, a subcutaneous injection administered every other day. Pharmacokinetic studies of these agents in children do not exist and available data are primarily from studies in healthy adults. It does not appear that the various formulations differ significantly in terms of bioavailability or efficacy in adults. The toxicity profiles of the interferon formulations are similar, with the most common adverse effects in children including flu-like symptoms, injection site reactions and transient elevations in liver enzymes. Glatiramer acetate is a mixture of synthetic polypeptide chains consisting of four different amino acids. Glatiramer acetate appears to mimic the antigenic properties of myelin basic protein (MBP), and by doing so, alters T-cell activation in the periphery. Glatiramer acetate is administered as a once-daily subcutaneous injection. Similar to the IFNß formulations, there are no pharmacokinetic studies of this agent in children. The most common adverse effects include injection site reactions and transient chest tightness. Fingolimod, a sphingosine 1-phosphate receptor modulator, is a new disease-modifying therapy that was approved by the US FDA in 2010 for the first-line treatment of relapsing forms of MS in adults. However, due to a lack of information and clinical data on this agent in the paediatric population, it is not included in this discussion. Dose-finding studies of the IFNs and glatiramer acetate in the paediatric population are limited. Dosing recommendations are largely based on tolerability studies, with most children and adolescents tolerating the full adult doses. Clinical studies of IFNs in children have not been objectively designed to establish the efficacy of these therapies, and evidence is limited to that of observational trials and retrospective case reports. However, the largest cohort (130 cases) of paediatric MS patients studied to date reported a reduction in annual relapse rate with all three of the different IFNß formulations and glatiramer acetate after a follow-up period of more than 4 years. Treatment with one of the first-line agents should be offered to any patient after the occurrence of a second demyelinating episode. The efficacy of the four first-line disease-modifying agents is considered to be relatively equivalent, and the choice of agent should be determined on an individual patient basis, taking into account potential adverse effects and patient preferences. Current data suggest that the IFNs and glatiramer acetate are safe and effective therapies in paediatric patients with MS. However, further studies evaluating the pharmacokinetics, appropriate dosing and comparisons of efficacy among these agents are needed to determine the most appropriate and evidence-based treatment decisions in this population.