Aminophylline Dosage In Asthma Exacerbations in Children: A Systematic Review

<div><p>Background</p><p>Adequate asthma treatment of childhood exacerbations with IV aminophylline depends on appropriate dosage. Recommendations to aim for a target therapeutic range may be inappropriate as serum concentrations correlate poorly with clinical improvement. This review aims to evaluate the evidence for the optimum dosage strategy of intravenous aminophylline in children suffering an exacerbation of asthma.</p><p>Methods</p><p>A systematic review comparing dosage regimens of intravenous aminophylline in children suffering an exacerbation of asthma. Primary outcomes were time until resolution of symptoms, mortality and need for mechanical ventilation. Secondary outcomes were date until discharge criteria are met, actual discharge and adverse effects.</p><p>Data sources</p><p>CENTRAL, CINAHL, MEDLINE and Web of Science. Search performed in March 2016</p><p>Eligibility criteria</p><p>Studies using intravenous aminophylline in children with an acute exacerbation of asthma which reported the dosage and clinical outcomes.</p><p>Findings</p><p>14 RCTs were included. There is a poor relationship between the dosage administered to children and symptom resolution, length of stay or need for mechanical ventilation. This study is limited due to its use of indirect evidence.</p><p>Conclusion</p><p>The currently recommended dosage regimens may not represent the optimum safety and efficacy of intravenous aminophylline. There is a need to develop the evidence base correlating dosage with patient centered clinical outcomes, to improve prescribing practices.</p></div

Design and conduct of early phase drug studies in children: challenges and opportunities

It has historically been very difficult to conduct early phase drug studies in children for a number of reasons related to ethics, acceptability, rarity, standardization, end points, safety, dosing and feasibility. Over the past decade there have been a number of developments including novel clinical trial design, in silico pharmacology and microdosing that have significantly enhanced the ability of investigators to conduct early phase drug studies in children. While the evolution of drug therapy is creating a series of new challenges, there has never been a better time for conducting drug studies in children

The Evidence for Intravenous Theophylline Levels between 10-20mg/L in Children Suffering an Acute Exacerbation of Asthma: A Systematic Review

<div><p>Background</p><p>Intravenous theophyllines are a second line treatment for children suffering an acute exacerbation of asthma. Various guidelines and formularies recommend aiming for serum theophylline levels between 10-20mg/l. This review aims to assess the evidence underpinning this recommendation.</p><p>Methods</p><p>A systematic review comparing outcomes of children who achieved serum theophylline concentrations between 10-20mg/l with those who did not. Primary outcomes were time until resolution of symptoms, mortality and need for mechanical ventilation. Secondary outcomes were date until discharge criteria are met, actual discharge, adverse effects and FEV1.</p><p>Data sources</p><p>MEDLINE, CINAHL, CENTRAL and Web of Science. Search performed in October 2015.</p><p>Eligibility criteria</p><p>Interventional or observational studies utilizing intravenous theophyllines for an acute exacerbation of asthma in children where serum theophylline levels and clinical outcomes were measured.</p><p>Findings</p><p>10 RCTs and 2 observational studies were included. Children with serum levels between 10-20mg/l did not have a reduction in duration of symptoms, length of hospital stay or need for mechanical ventilation or better spirometric results compared with levels <10mg/l. Levels above 20mg/l are not associated with higher rates of adverse effects. This study is limited due to heterogeneity in the way theophylline levels were reported and poor surveillance of adverse effects across studies.</p><p>Conclusion</p><p>Dosing strategies aiming for levels between 10-20mg/l are not associated with better outcomes. Clinicians should rely on clinical outcomes and not serum levels when using intravenous theophyllines in children suffering an acute exacerbation of asthma.</p></div

Prioritising neonatal medicines research: UK Medicines for Children Research Network scoping survey

BACKGROUND: The dosing regimen and indications for many medicines in current use in neonatology are not well defined. There is a need to prioritise research in this area, but currently there is little information about which drugs are used in UK neonatal units and the research needs in this area as perceived by UK neonatologists. METHODS: The Neonatal Clinical Studies Group (CSG) of the Medicines for Children Research Network (MCRN) undertook a 2 week prospective scoping survey study to establish which medicines are used in UK neonatal units; how many babies are receiving them; and what clinicians (and other health professionals) believe are important issues for future research. RESULTS: 49 out of 116 units responded to at least one element of the survey (42%). 37 units reported the number of neonates who received medicines over a 2 week period. A total of 3924 medicine-patient pairs were reported with 119 different medicines. 70% of medicine-patient pairs involved medicines that were missing either a license or dose for either term or preterm neonates. 4.3% of medicine-patient pairs involved medicines that were missing both license and dose for any neonate. The most common therapeutic gap in need of additional research identified by UK neonatologists was chronic lung disease (21 responding units), followed by patent ductus arteriosus and vitamin supplements (11 responding units for both) CONCLUSION: The research agenda for neonatal medicines can be informed by knowledge of current medicine use and the collective views of the neonatal community

Improving the quality of written information available at weekends in a paediatric hospital: the TRANSMIT sheet.

The clinical outcomes at weekends are worse than during the week in a hospital setting. There are many potential factors which influence this. High quality communication between the weekday teams and the on call weekend staff could help improve clinical outcomes at weekends, but there are no validated forms of communication that have been established in a paediatric hospital setting. The casenotes of all medical patients (n=119) were prospectively evaluated across all medical wards in a large paediatric hospital over three weekends, to establish the quality of information available to on call teams. Following introduction of structured documentation, known as a TRANSMIT (including Tasks, Respiratory, Anticipated problems, Nutrition, Sepsis, Medication, Intravenous access, Transfer/discharge) sheet, the audit was repeated (n=111). A qualitative survey of junior doctors using TRANSMIT was carried out after introduction. Prior to the introduction of the structured documentation (TRANSMIT sheet) an accurate problem list was present in 56% (67/119), and an adequate written management plan in 63% (75/119). Following introduction, an improvement in the notes was seen, with accurate problem lists in 82% (91/111) and an adequate plan in 76% (84/111). Improvements in the quantity and quality of information available to weekend on call medical staff were noted. The use of a structured documentation (TRANSMIT sheet) can improve the quality of written information available to on-call teams in a paediatric hospital setting. A retrospective qualitative assessment of junior doctors using TRANSMIT sheets showed an improvement in both the quantity and quality of information available to on call staff at weekends

Childhood asthma exacerbations and the Arg16 b2-receptor polymorphism: a meta-analysis stratified by treatment

Background: The Gly-to-Arg substitution at the 16 position (rs1042713) in the b2-adrenoceptor gene (ADRB2) is associated with enhanced downregulation and uncoupling of b2-receptors. Objectives: We sought to undertake a meta-analysis to test the hypothesis that there is an interaction between the A allele of rs1042713 (Arg16 amino acid) and long-acting b-agonist (LABA) exposure for asthma exacerbations in children. Methods: Children with diagnosed asthma were recruited in 5 populations (BREATHE, Genes-Environments and Admixture in Latino Americans II, PACMAN, the Paediatric Asthma Gene Environment Study, and the Pharmacogenetics of Adrenal Suppression with Inhaled Steroid Study). A history of recent exacerbation and asthma treatment was determined from questionnaire data. DNA was extracted, and the Gly16Arg genotype was determined. Results: Data from 4226 children of white Northern European and Latino origin were analyzed, and the odds ratio for exacerbation increased by 1.52 (95% CI, 1.17-1.99; P 5 .0021) for each copy of the A allele among the 637 children treated with inhaled corticosteroids (ICSs) plus LABAs but not for treatment with ICSs alone (n 5 1758) or ICSs plus leukotriene receptor antagonist (LTRAs; n 5 354) or ICSs plus LABAs plus LTRAs (n 5 569). Conclusions: The use of a LABA but not an LTRA as an ‘‘addon controller’’ is associated with increased risk of asthma exacerbation in children carrying 1 or 2 A alleles at rs1042713. Prospective genotype-stratified clinical trials are now required to explore the potential role of rs1042713 genotyping for personalized asthma therapy in children. (J Allergy Clin Immunol 201

WHAT DOMAINS RELATED TO MEDICINES WERE MEASURED IN STUDIES OF BURDEN OF CARE FOR PAEDIATRIC PATIENTS? A SYSTEMATIC REVIEW

IntroductionMedicines are becoming increasingly common for all populations and polypharmacy has been shown to have numerous risks. Although primary studies and reviews have explored the impact of medical conditions on patients and caregivers, there are no known reviews on the impact of medicines on paediatric patients. This systematic review therefore aimed to determine the domains commonly assessed in studies assessing treatment burden in different conditions for paediatric patients and their caregivers.MethodsSearches were conducted on Medline, CINAHL, EMBASE, Web of Science and Cochrane Database of Systematic Reviews to find relevant papers. Two reviewers independently screened the papers based on the chosen inclusion and exclusion criteria. The quality of the papers was assessed independently by two reviewers using the Newcastle Ottawa Scale. This review was registered with PROSPERO (PROSPERO registration number: CRD42021285097) and conducted according to PRISMA methodology.Results6 papers with 8276 participants were identified in this review. The domains most commonly assessed were the perceived effectiveness of medications (4/6 studies), psychosocial impact (3/6 studies) and the impact on work and school (3/6 studies). Other domains included the ease of use of medicines, side effects from medicines, adherence to medicines, time requirements, costs, using healthcare resources and support from family/friends/organisations.ConclusionsStudies assessing the burden of care due to medicines assessed a range of domains related to the impact of medicines on patients and caregivers. The results from this review will be used create a questionnaire for a cohort study that aims to determine the impact of polypharmacy on paediatric patients and their parents.</jats:sec

Readability of paediatric participant information leaflets in research studies

Background: Information leaflets in research studies should be age-appropriate to be understood, however the formal readability of children’s participant information leaflets (PILs) for research studies has not been assessed. // Methods: A single-centre cross-sectional study assessing paediatric PILs. Six readability tests were applied (Gunning Fog Index (GFI), Simple Measure of Gobbledygook (SMOG), Flesch Kincaid Grade Level (FKGL), Coleman–Liau Index (CLI), Automated Readability Index (ARI) and Flesch Reading Ease score (FRE). Results were compared between age groups, and whether the PIL was from either a commercially sponsored or investigator led study. // Results: 191 paediatric PILs were included. Age categories; <10 years (n = 65), ≤12 (n = 73), ≤15 (n = 73) and ≥16 (n = 61); were used for analysis. There were 39 commercial PILs and 226 non-commercial PILs. For the ≤10 and ≤12 age bands, all 6 median readability scores exceeded the target age group (thus hard to read, p < 0.005), and there was no difference in readability scores between these two age bands. Four scores from the readability tests were considered age-appropriate in the ≤15 year category, and all median scores were age-appropriate in the ≥16 years age groups. Readability scores for children’s PILs were significantly higher in commercially sponsored versus non-commercial studies (P < 0.005). // Conclusion: Improvements are required to make children’s PILs readable for the target audience, particularly in commercially sponsored research studies. // Impact: Paediatric participant information leaflets may not be readable in research studies, especially in younger age groups. PILs for children participating in commercially sponsored studies were less readable than non-commercial studies. Research teams writing PILs for a paediatric study need to consider the use of readability tools to ensure that the information they are providing is readable by the target audience

DEPRESCRIBING LONG ACTING BETA2 AGONISTS INCHILDREN AND ADOLESCENTS WITH STABLE ASTHMA:A SYSTEMATIC REVIEW

IntroductionWe sought to detect a relationship between midazolam concentration and development of new delirium in critically ill children who were on continuous midazolam administration.MethodsDelirium was detected using the Sophia Observation withdrawal Symptoms - Paediatric Delirium (SOS-PD) score and 104 left-over samples were available to measure midazolam concentrations.ResultsTwenty-five percent of the included patients developed new delirium. Median cumulative midazolam dose was higher in patients who developed delirium compared to those without delirium but lower compared with the day preceding delirium detection, indicative of a rapid decline. Similar findings were made when active metabolites 1-hydroxymidazolam and 1-hydroxymidazolam glucuronide were considered.ConclusionsA sudden and significant reduction in midazolam concentration may contribute to the development of a delirium in critically ill children. </jats:sec