This European Respiratory Society statement provides a comprehensive overview on protracted bacterial bronchitis (PBB) in children. A task force of experts, consisting of clinicians from Europe and ...Australia who manage children with PBB determined the overall scope of this statement through consensus. Systematic reviews addressing key questions were undertaken, diagrams in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement constructed and findings of relevant studies summarised. The final content of this statement was agreed upon by all members.The current knowledge regarding PBB is presented, including the definition, microbiology data, known pathobiology, bronchoalveolar lavage findings and treatment strategies to manage these children. Evidence for the definition of PBB was sought specifically and presented. In addition, the task force identified several major clinical areas in PBB requiring further research, including collecting more prospective data to better identify the disease burden within the community, determining its natural history, a better understanding of the underlying disease mechanisms and how to optimise its treatment, with a particular requirement for randomised controlled trials to be conducted in primary care.
Project Aim
To retrospectively evaluate a clinical management algorithm for acute wheezers in a UK Pediatric Emergency Department (PED).
Overview and Rationale
Acute wheezing attacks are a leading ...cause of PED attendances and inpatient admissions. Prednisolone, a routine treatment, is intolerable in almost one‐third of children, requiring repeated dosing, which may prolong length of stay (LOS). To address this problem, we: (1) developed an acute management algorithm (concise, single‐sided flow‐chart, instructing immediate management); (2) modified the OCS regime from prednisolone (1 mg/kg, 3‐day course) to dexamethasone (600 then 300 mcg/kg); (3) and disseminated guidance regionally. Written information—handouts, e‐mails, and posters—were followed‐up with verbal reinforcement. We implemented the algorithm in 2017 and revised it further in 2018.
Evaluation
In 2019, we retrospectively collected data on 100 acute wheeze attendances (those requiring OCS, aged 2–14), between October and December in 2016, 2017, and 2018 (n = 300), and assessed outcomes.
Results
Over a 48‐month period, we reduced OCS intolerability by 67.2% and OCS drug costs by 85.8% (saving £41,470.14), while not significantly influencing the other outcomes.
Conclusions
Reduced intolerability and substantial cost savings can be achieved by implementing a structured acute pediatric wheeze algorithm and modifying the OCS to single‐dose dexamethasone (300 mcg/kg).
A Meta-Analysis of the Association Between Childhood Type 1 Diabetes and Atopic Disease
Chris R. Cardwell , MSC 1 ,
Mike D. Shields , MD 2 ,
Dennis J. Carson , MB 2 and
Chris C. Patterson , PHD 1
1 ...Department of Epidemiology & Public Health, Queen’s University of Belfast, Belfast, Northern Ireland, U.K
2 Department of Child Health, Queen’s University of Belfast, Belfast, Northern Ireland, U.K
Address correspondence and reprint requests to Chris Cardwell, Department of Epidemiology & Public Health, The Queen’s University
of Belfast, Grosvenor Road, Belfast BT12 6BJ, U.K. E-mail: c.cardwell{at}qub.ac.uk
Abstract
OBJECTIVE —To review the published literature and perform a meta-analysis summarizing the evidence in support of an inverse association
between type 1 diabetes and the atopic disorders: asthma, eczema, and allergic rhinitis in children.
RESEARCH DESIGN AND METHODS —MEDLINE, Web of Science, and PubMed were searched to identify relevant studies. These were assessed on quality criteria,
and odds ratios (ORs) and 95% CIs were calculated for each study from the reported prevalences of atopy in children with diabetes
and in control children. Meta-analysis was then used to derive a combined OR and test for heterogeneity in findings between
studies.
RESULTS —Twenty-five studies were identified. Heterogeneity in the findings from different studies was evident but was considerably
reduced when the asthma and rhinitis analyses were restricted to those studies judged to be of adequate design. The meta-analysis
revealed an inverse association between asthma and type 1 diabetes, but the finding only attained significance when analysis
was restricted to the studies of adequate design (OR 0.82, 95% CI 0.68–0.99). In this subset an association of similar magnitude
was observed between eczema and type 1 diabetes (0.82, 0.62–1.10) although this failed to attain statistical significance,
and heterogeneity between studies was still present. There was little evidence of an association between rhinitis and type
1 diabetes (0.97, 0.82–1.16) in this subset of studies.
CONCLUSIONS —Our analysis suggests that there is a small but significant reduction in the prevalence of asthma in children with type 1
diabetes, but the findings for the other atopic diseases are less conclusive.
Th1, T helper type 1
Th2, T helper type 2
Footnotes
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
Accepted June 16, 2003.
Received April 17, 2003.
DIABETES CARE
Aims
To characterize the population pharmacokinetics of ranitidine in critically ill children and to determine the influence of various clinical and demographic factors on its disposition.
Methods
...Data were collected prospectively from 78 paediatric patients (n = 248 plasma samples) who received oral or intravenous ranitidine for prophylaxis against stress ulcers, gastrointestinal bleeding or the treatment of gastro‐oesophageal reflux. Plasma samples were analysed using high‐performance liquid chromatography, and the data were subjected to population pharmacokinetic analysis using nonlinear mixed‐effects modelling.
Results
A one‐compartment model best described the plasma concentration profile, with an exponential structure for interindividual errors and a proportional structure for intra‐individual error. After backward stepwise elimination, the final model showed a significant decrease in objective function value (−12.618; P < 0.001) compared with the weight‐corrected base model. Final parameter estimates for the population were 32.1 l h−1 for total clearance and 285 l for volume of distribution, both allometrically modelled for a 70 kg adult. Final estimates for absorption rate constant and bioavailability were 1.31 h−1 and 27.5%, respectively. No significant relationship was found between age and weight‐corrected ranitidine pharmacokinetic parameters in the final model, with the covariate for cardiac failure or surgery being shown to reduce clearance significantly by a factor of 0.46.
Conclusions
Currently, ranitidine dose recommendations are based on children's weights. However, our findings suggest that a dosing scheme that takes into consideration both weight and cardiac failure/surgery would be more appropriate in order to avoid administration of higher or more frequent doses than necessary.
To characterize the population pharmacokinetics of canrenone following administration of potassium canrenoate (K-canrenoate) in paediatric patients.
Data were collected prospectively from 37 ...paediatric patients (median weight 2.9 kg, age range 2 days-0.85 years) who received intravenous K-canrenoate for management of retained fluids, for example in heart failure and chronic lung disease. Dried blood spot (DBS) samples (n=213) from these were analysed for canrenone content and the data subjected to pharmacokinetic analysis using nonlinear mixed-effects modelling. Another group of patients (n=16) who had 71 matching plasma and DBS samples was analysed separately to compare canrenone pharmacokinetic parameters obtained using the two different matrices.
A one-compartment model best described the DBS data. Significant covariates were weight, postmenstrual age (PMA) and gestational age. The final population models for canrenone clearance (CL/F) and volume of distribution (V/F) in DBS were CL/F (l/h) = 12.86 × (WT/70.0) × e 0.066 × (PMA - 40) and V/F (l) = 603.30 × (WT/70) × (GA/40) where weight is in kilograms. The corresponding values of CL/F and V/F in a patient with a median weight of 2.9 kg are 1.11 l/h and 20.48 l, respectively. Estimated half-life of canrenone based on DBS concentrations was similar to that based on matched plasma concentrations (19.99 and 19.37 h, respectively, in 70 kg patient).
The range of estimated CL/F in DBS for the study population was 0.12-9.62 l/h; hence, bodyweight-based dosage adjustment of K-canrenoate appears necessary. However, a dosing scheme that takes into consideration both weight and age (PMA/gestational age) of paediatric patients seems more appropriate.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• Little is known about the pharmacokinetics of potassium canrenoate/canrenone in paediatric patients
WHAT THIS STUDY ADDS
• A population pharmacokinetic ...model has been developed to evaluate the pharmacokinetics of canrenone in paediatric patients who received potassium canrenoate as part of their therapy in the intensive care unit.
AIMS To characterize the population pharmacokinetics of canrenone following administration of potassium canrenoate to paediatric patients.
METHODS Data were collected prospectively from 23 paediatric patients (2 days to 10 years of age; median weight 4 kg, range 2.16–28.0 kg) who received intravenous potassium canrenoate (K‐canrenoate) as part of their intensive care therapy for removal of retained fluids, e.g. in pulmonary oedema due to chronic lung disease and for the management of congestive heart failure. Plasma samples were analyzed by HPLC for determination of canrenone (the major metabolite and pharmacologically active moiety) and the data subjected to pharmacokinetic analysis using NONMEM.
RESULTS A one compartment model best described the data. The only significant covariate was weight (WT). The final population models for canrenone clearance (CL/F) and volume of distribution (V/F) were CL/F (l h−1) = 11.4 × (WT/70.0)0.75 and V/F (l) = 374.2 × (WT/70) where WT is in kg. The values of CL/F and V/F in a 4 kg child would be 1.33 l h−1 and 21.4 l, respectively, resulting in an elimination half‐life of 11.2 h.
CONCLUSIONS The range of estimated CL/F in the study population was 0.67–7.38 l h−1. The data suggest that adjustment of K‐canrenoate dosage according to body weight is appropriate in paediatric patients.
Abstract
Ionophores are a separate class of non-medically important antibiotics used in animal production to increase growth rate. Narasin (Skycis; Elanco Animal Health, Greenfield, IN) is an ...ionophore labeled for increased rate of body weight gain and improved feed efficiency in growing-finishing swine. The mode of action of this ionophore is to increase energy availability by altering volatile fatty acid production in the hindgut in favor of propionate, which is the most efficient product of fermentation. Therefore, a meta-regression analysis was conducted to evaluate the effects of narasin inclusion in growing-finishing pig diets to predict average daily gain and feed efficiency. A database was developed that contained 21 papers from 2012 to 2021 representing 308 observations including both individual period data as well as overall trial data. For statistical analysis two models were created. The individual period model considered only data with single continuous narasin feeding periods while the overall trial model considered complete data sets representing periods with and without narasin feeding. Regression model equations were developed with the GLIMMIX procedure of SAS (Version 9.4, SAS institute, Cary, NC). Predictor variables were assessed with a step-wise manual forward selection for model inclusion. Predictor variables were required to provide an improvement of at least 2 Bayesian information criterion units to be included in the final model. For individual period data for G:F, the model selected included concentration of narasin in the feed, ADG and ADFI of the control group not provided narasin, and average BW of the control group categorized into greater than 105 kg or less than 105 kg (Table 1). There were 2 competing models to predict improvement in overall G:F. For model 1, significant predictors included concentration of narasin in feed and ADG of the control group. Model 2 for overall G:F included concentration of narasin in feed, ADG and ADFI of the control group. For the individual period model that predicted ADG, the predictors were concentration of narasin in the feed, ADFI, G:F of the control group and BW category for feeding period. The best fitting ADG model using the overall trial data included concentration of narasin in feed, ADFI and G:F of the control group, and feeding duration categorized as longer than 65 days or shorter than 65 days. Together, these models can be used to predict the response to narasin supplementation in finishing pigs. Based on the results, the overall response to narasin inclusion rate for ADG and G:F is quadratic in nature. Additionally, as ADG and G:F increase, the response to narasin supplementation decreases. In summary, using average values from the database for predictor variables, this meta-analysis demonstrates narasin would be expected to improve overall G:F from 0.74 to 1.13% and ADG from 1 to 3%.
Background: The marked increases in the incidence of type 1 diabetes in recent decades strongly suggest the role of environmental influences. These environmental influences remain largely unknown.
...Objective: To investigate atopy and home environment (such as children living at home, sharing a bedroom and house moves) as potential risk factors for type 1 diabetes.
Subjects and method: In Northern Ireland, 175 children with type 1 diabetes and 4859 control children completed a questionnaire on atopy experience, family composition and home environment. Control children from two age groups (6–8 yr old and 13–14 yr old) were identified from randomly selected primary and secondary schools across Northern Ireland. Cases were identified from a population‐based type 1 diabetes register.
Results: There was little evidence of a difference in the proportion of participants with a history of atopy in the cases compared with controls. There was a significant reduction in the risk of diabetes in children who lived with more siblings {odds ratio (OR) = 0.58 95% confidence interval (95% CI) 0.39–0.85 in children who lived with three or more siblings compared with one or none} and in children who moved house more often OR = 0.59 (95% CI 0.40–0.88) in children who moved house twice or more compared with never.
Conclusion: The reduced risk of type 1 diabetes in children living with siblings, sharing a bedroom and moving house more often could reflect the protection afforded by exposure to infections in early life and consequently may provide support for the hygiene hypothesis.
Abstract Ionophores are feed additives that decrease gram-positive microbial populations by disrupting the ion transfer across cell membranes resulting in improved growth performance. Narasin ...(Skycis; Elanco Animal Health, Greenfield, IN) is an FDA-approved ionophore utilized for increased rate of weight gain and improved feed efficiency in growing-finishing pigs. A meta-regression analysis was conducted to evaluate the effects of added narasin in growing-finishing pig diets to predict its influence on average daily gain (ADG), feed efficiency (G:F), and carcass yield. A database was developed containing 21 technical reports, abstracts, and refereed papers from 2012 to 2021 representing 35 observations for growth performance data in studies ranging from 35 to 116 d in length (overall data). In addition, within these 35 observations, individual period data were evaluated (143 observations) using weekly, bi-weekly, or monthly performance intervals (period data). Regression model equations were developed, and predictor variables were assessed with a stepwise manual forward selection procedure. The ADG model using the overall data included ADG, ADFI, and G:F of the control group, added narasin dose, and narasin feeding duration categorized as longer or shorter than 65 d. Predictor variables included in the G:F model using overall data were ADG, ADFI, and G:F of the control group and added narasin dose. For carcass yield, the final model included ADFI and G:F of the control group, added narasin dose, and narasin feeding duration of longer than 65 d. In the period model for ADG, the predictors included ADG, ADFI, and G:F of the control group, added narasin dose, and average BW of the control group categorized into greater than or less than 105 kg. For period data for G:F, the model selected ADG, ADFI, and G:F of the control group and added narasin dose. Based on the results, the overall response to added narasin for ADG and G:F was quadratic and tended to decrease as ADG and G:F increased. A similar quadratic response was observed for the individual period data. In summary, using median values from the database for predictor variables, this meta-analysis demonstrated narasin would be expected to improve ADG between 1.06% and 1.65%, G:F between 0.71% and 1.71%, and carcass yield by 0.31% when fed continuously for longer than 65 d.
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