Implementation of clinical decision support in young children with acute gastroenteritis: a randomized controlled trial at the emergency department

textabstractAcute gastroenteritis (AGE) is one of the most frequent reasons for young children to visit emergency departments (EDs). We aimed to evaluate (1) feasibility of a nurse-guided clinical decision support system for rehydration treatment in children with AGE and (2) the impact on diagnostics, treatment, and costs compared with usual care by attending physician. A randomized controlled trial was performed in 222 children, aged 1 month to 5 years at the ED of the Erasmus MC-Sophia Children’s hospital in The Netherlands ( 2010–2012). Outcome included (1) feasibility, measured by compliance of the nurses, and (2) length of stay (LOS) at the ED, the number of diagnostic tests, treatment, follow-up, and costs. Due to failure of post-ED weight measurement, we could not evaluate weight difference as measure for dehydration. Patient characteristics were comparable between the intervention (N = 113) and the usual care group (N = 109). Implementation of the clinical decision support system proved a high compliance rate. The standardized use of oral ORS (oral rehydration solution) significantly increased from 52 to 65%(RR2.2, 95%CI 1.09–4.31 p < 0.05). We observed no differences in other outcome measures. Conclusion: Implementation of nurse-guided clinical decision support system on rehydration treatment in children with AGE showed high compliance and increase standardized use of ORS, without differences in other outcome measures.(Table presented.

Characteristics of revisits of children at risk for serious infections in pediatric emergency care

In this study, we aimed to identify characteristics of (unscheduled) revisits and its optimal time frame after Emergency Department (ED) discharge. Children with fever, dyspnea, or vomiting/diarrhea (1 month–16 years) who attended the ED of Erasmus MC-Sophia, Rotterdam (2010–2013), the Netherlands, were prospectively included. Three days after ED discharge, we applied standardized telephonic questionnaires on disease course and revisits. Multivariable logistic regression analysis was used to identify independent characteristics of revisits. Young age, parental concern, and alarming signs and symptoms (chest wall retractions, ill appearance, clinical signs of dehydration, and tachypnea) were associated with revisits (n = 527) in children at risk for serious infections discharged from the ED (n = 1765). Children revisited the ED within a median of 2 days (IQR 1.0–3.0), but this was proven to be shorter in children with vomiting/diarrhea (1.0 day (IQR 1.0–2.0)) compared to children with fever or dyspnea (2.0 (IQR 1.0–3.0)). Conclusion: Young age, parental concern, and alarming signs and symptoms (chest wall retractions, ill appearance, clinical signs of dehydration, and tachypnea) were associated with emergency health care revisits in children with fever, dyspnea, and vomiting/diarrhea. These characteristics could help to define targeted review of children during post-discharge period. We observed a disease specific and differential timing of control revisits after ED discharge.(Table presented.

Tools for 'safety netting' in common paediatric illnesses: A systematic review in emergency care

Context Follow-up strategies after emergency department (ED) discharge, alias safety netting, is often based on the gut feeling of the attending physician. Objective To systematically identify evaluated safetynetting strategies after ED discharge and to describe determinants of paediatric ED revisits. Data sources MEDLINE, Embase, CINAHL, Cochrane central, OvidSP, Web of Science, Google Scholar, PubMed. Study selection Studies of any design reporting on safety netting/follow-up after ED discharge and/or determinants of ED revisits for the total paediatric population or specifically for children with fever, dyspnoea and/or gastroenteritis. Outcomes included complicated course of disease after initial ED visit (eg, revisits, hospitalisation). Data extraction Two reviewers independently assessed studies for eligibility and study quality. As meta-analysis was not possible due to heterogeneity of studies, we performed a narrative synthesis of study results. A best-evidence synthesis was used to identify the level of evidence. Results We summarised 58 studies, 36% (21/58) were assessed as having low risk of bias. Limited evidence was observed for different strategies of safety netting, with educational interventions being mostly studied. Young children, a relevant medical history, infectious/ respiratory symptoms or seizures and progression/ persistence of symptoms were strongly associated with ED revisits. Gender, emergency crowding, physicians' characteristics and diagnostic tests and/or therapeutic interventions at the index visit were not associated with revisits. Conclusions Within the heterogeneous available evidence, we identified a set of strong determinants of revisits that identify high-risk groups in need for safety netting in paediatric emergency care being related to age and clinical symptoms. Gaps remain on intervention studies concerning specific application of a uniform safety-netting strategy and its included time frame

Clinicians’ overestimation of febrile child risk assessment

We aimed to estimate clinicians’ based risk thresholds at which febrile children would be managed as serious bacterial infections (SBI) to determine influencing characteristics and to compare thresholds with prediction model (Feverkidstool) risk estimates. Twenty-one video vignettes of febrile children visiting the emergency department (ED) were assessed by 42 (40.4 %) international paediatricians/paediatric emergency clinicians. Questions were related to clinical risk scores of the child having SBI and SBI management decisions on visual analogue scales. Feverkidstool risk scores were based on clinical signs/symptoms and C-reactive protein. Amongst vignettes assigned to SBI management, the median risk was 60 % (interquartile range (IQR) 30.0–80.5) and 16.0 % (IQR 5.0–32.0) when vignettes were not managed as SBI. Ill appearance and aberrant circulatory signs were the most influencing factors, as age and duration of fever were the least influencing factors on SBI management decisions. Feverkidstool risk scores varied from 13 % (IQR 7.7–28.1) for SBI management to 7.3 % (IQR 5.7–16.3) for no SBI management. Conclusion: Clinicians assigned high risk scores to children who they would have managed as SBI, mostly influenced by ill appearance and aberrant circulation. In contrast to SBI risk assessment of the Feverkidstool, clinicians’ appeared to apply a more stepwise assessment of the risk of presence/absence of SBI at different steps in the diagnostic and therapeutic process. Uniform risk thresholds at which one should start SBI management in febrile children remains unclear; risk thresholds at which we refrained from SBI management were more consistent

Safety of Growth Hormone Replacement Therapy in Childhood-Onset Craniopharyngioma:A Systematic Review and Cohort Study

Introduction: Survival of childhood-onset craniopharyngioma (cCP) is excellent; however, many survivors suffer from hypothalamic-pituitary dysfunction. Growth hormone replacement therapy (GHRT) is of high importance for linear growth and metabolic outcome. Optimal timing for initiation of GHRT in cCP is on debate because of concerns regarding tumor progression or recurrence.Methods: A systematic review and cohort studys were performed for the effect and timing of GHRT on overall mortality, tumor progression/recurrence, and secondary tumors in cCP. Within the cohort, cCP receiving GHRT ≤1 year after diagnosis were compared to those receiving GHRT &gt;1 year after diagnosis.Results: Evidence of 18 included studies, reporting on 6,603 cCP with GHRT, suggests that GHRT does not increase the risk for overall mortality, progression, or recurrent disease. One study evaluated timing of GHRT and progression/recurrence-free survival and found no increased risk with earlier initiation. One study reported a higher than expected prevalence of secondary intracranial tumors compared to a healthy population, possibly confounded by radiotherapy. In our cohort, 75 of 87 cCP (86.2%) received GHRT for median of 4.9 years [0.0-17.1]. No effect of timing of GHRT was found on mortality, progression/recurrence-free survival, or secondary tumors.Conclusion: Although the quality of the evidence is low, the available evidence suggests no effect of GHRT or its timing on mortality, tumor progression/recurrence, or secondary neoplasms in cCP. These results support early initiation of GHRT in cCP aiming to optimize linear growth and metabolic outcome. Prospective studies are needed to increase the level of evidence upon the optimal timing to start GHRT in cCP patients.</p

A simple extemporaneous oral suspension of aprepitant yields sufficient pharmacokinetic exposure in children

Introduction: Aprepitant is used for the treatment of chemotherapy induced nausea and vomiting. A liquid formulation is needed for treatment of young children. However, the commercial (powder for) suspension was not available worldwide for a prolonged period of time and, therefore, a 10 mg/mL aprepitant oral suspension was extemporarily prepared to prevent suboptimal antiemetic treatment. The current pharmacokinetic study was developed to investigate whether this extemporaneous oral suspension offers an appropriate treatment option.Methods: From 49 pediatric patients (0.7–17.9 years) 235 plasma concentrations were collected. Patients were either treated with our extemporaneous oral suspension (n = 26; 53%), commercially available capsules (n = 18; 37%), or the intravenous prodrug formulation of aprepitant (fosaprepitant, n = 5; 10%). Pharmacokinetic analyses were performed using nonlinear mixed effects modelling.Results: A one-compartment model adequately described the pharmacokinetics of aprepitant in children. The bioavailability of the extemporaneous oral suspension was not significantly different to that of the capsules (P = 0.26). The observed bioavailability throughout the total population was 83% (95% CI 69%-97%). The absorption of the extemporaneous oral suspension was 39.4% (95%CI 19.5–57.4%) faster than that of capsules (mean absorption time of 1.78 h (95%CI 1.32–2.35), but was comparable to that of the commercial oral suspension. The median area under the curve after (fos)aprepitant was 22.2 mg/L*h (range 8.9–50.3 mg/L*h) on day 1.Conclusion: Our extemporaneous oral suspension is an adequate alternative for the commercially (un)available oral suspension in young children. An adequate exposure to aprepitant in children was yielded and the bioavailability of the extemporaneous suspension was comparable to capsules.</p

Nausea and nausea-related symptoms in children with cancer: Presence, severity, risk factors and impact on quality of life during the first year of treatment

Aims: Identify 1) presence of nausea and nausea-related symptoms and its relationship with health-related quality of life (HRQoL), and 2) severity of nausea and associations with patient-related factors in children with cancer during the first year of treatment. Methods: A historical cohort study of 781 patients with cancer (2–21 years) was conducted. Presence and severity of nausea were assessed at 3, 6, 9, and 12 months after diagnosis using the nausea scale of the PedsQL3.0 Cancer Module, comprising 5 symptoms, using proxy-report (2–7 years) or self-report (8–21 years). Multivariable multilevel analyses were performed to evaluate the association between patient-related factors and nausea. Overall HRQoL (generic PedsQL) was compared between children with presence and absence of nausea related-symptoms. Results: The presence of nausea during medical treatment was highest at 6 months after diagnosis (42.9 %). Highest symptom presence was seen on the item “food not tasting good” (range 51.6 %−62.8 %). For all nausea-related symptoms, average HRQoL scores were 9.9–14.4 points lower for patients with symptoms compared to patients without symptoms.Pain, treatment anxiety, and worry were significantly associated with nausea in all children. In patients aged 8–21 years, male gender, a solid tumor, and BMI were associated with nausea. Patients with solid tumors were at higher risk of nausea compared to patients with hematological malignancies or brain/CNS tumors. Patients with a high BMI reported less nausea compared to patients with a normal BMI. Conclusion: Nausea is still a major problem in children with cancer and has a negative impact on HRQoL

Overestimation of the effect of (fos)aprepitant on intravenous dexamethasone pharmacokinetics requires adaptation of the guidelines for children with chemotherapy-induced nausea and vomiting

Purpose: Chemotherapy-induced nausea and vomiting (CINV) are common side effects in pediatric oncology treatment. Besides 5-HT3-antagonists, both dexamethasone and aprepitant are cornerstone drugs in controlling these side effects. Based on results of adult studies, the dexamethasone dose is reduced by 50% when combined with aprepitant, because of a drug-drug interaction, even though data on the interaction in children is lacking. The current study was developed to investigate the effect of aprepitant on dexamethasone clearance (CL) in children, in order to assess if dexamethasone dose reduction for concomitant use of aprepitant is appropriate in the current antiemetic regimen. Methods: In total, 65 children (0.6–17.9 years), receiving intravenous or oral antiemetic therapy (dexamethasone ± aprepitant) as standard of care, were included. 305 dexamethasone plasma concentrations were determined using LC–MS/MS. An integrated dexamethasone and aprepitant pharmacokinetic model was developed using non-linear mixed effects modelling in order to investigate the effect of aprepitant administration on dexamethasone CL. Results: In this population, dexamethasone CL in patients with concomitant administration of aprepitant was reduced by approximately 30% of the uninhibited CL (23.3 L/h (95% confidence interval 20.4–26.0)). This result is not consistent with the results of adult studies (50% reduction). This difference was not age dependent, but might be related to the route of administration of dexamethasone. Future studies are needed to assess the difference in oral/intravenous dexamethasone. Conclusion: When dexamethasone is given intravenously as a component of triple therapy to prevent CINV in children, we advise to reduce the dexamethasone dose by 30% instead of 50%

Impact of a Clinical Decision Model for Febrile Children at Risk for Serious Bacterial Infections at the Emergency Department: A Randomized Controlled Trial

<div><p>Objectives</p><p>To assess the impact of a clinical decision model for febrile children at risk for serious bacterial infections (SBI) attending the emergency department (ED).</p><p>Methods</p><p>Randomized controlled trial with 439 febrile children, aged 1 month-16 years, attending the pediatric ED of a Dutch university hospital during 2010-2012. Febrile children were randomly assigned to the intervention (clinical decision model; n=219) or the control group (usual care; n=220). The clinical decision model included clinical symptoms, vital signs, and C-reactive protein and provided high/low-risks for “pneumonia” and “other SBI”. Nurses were guided by the intervention to initiate additional tests for high-risk children. The clinical decision model was evaluated by 1) area-under-the-receiver-operating-characteristic-curve (AUC) to indicate discriminative ability and 2) feasibility, to measure nurses’ compliance to model recommendations. Primary patient outcome was defined as correct SBI diagnoses. Secondary process outcomes were defined as length of stay; diagnostic tests; antibiotic treatment; hospital admission; revisits and medical costs.</p><p>Results</p><p>The decision model had good discriminative ability for both pneumonia (n=33; AUC 0.83 (95% CI 0.75-0.90)) and other SBI (n=22; AUC 0.81 (95% CI 0.72-0.90)). Compliance to model recommendations was high (86%). No differences in correct SBI determination were observed. Application of the clinical decision model resulted in less full-blood-counts (14% vs. 22%, p-value<0.05) and more urine-dipstick testing (71% vs. 61%, p-value<0.05).</p><p>Conclusions</p><p>In contrast to our expectations no substantial impact on patient outcome was perceived. The clinical decision model preserved, however, good discriminatory ability to detect SBI, achieved good compliance among nurses and resulted in a more standardized diagnostic approach towards febrile children, with less full blood-counts and more rightfully urine-dipstick testing.</p><p>Trial Registration</p><p>Nederlands Trial Register <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2381" target="_blank">NTR2381</a></p></div