bluuebunny/crossref_metadata_2025_split huggingface dataset:
P105 Ambulatory study center at the University of Basel Children’s Hospital (UKBB)
Authors: Werner C , Santoro R , Bielicki J 
Published: May 2019

BackgroundMany drugs authorized in Europe and the United States are inadequately studied in children. SwissPedNet Funding has boosted the development of specialized and professional pediatric centers for clinical studies in Switzerland tasked with executing compliant, reliable and family-centered clinical research. The University of Basel Children`s Hospital (UKBB) is one of the pediatric clinical study centers.MethodsThe Department for Clinical Research in Basel consists of the study center for adults at University Hospital Basel (USB) and the Ambulatory Study Center (ASZ) focusing on pediatric studies at the UKBB. The latter was established in 2015, and consists of a specialized team, including a medical director, medical coordinator, medical specialists in pediatrics as well as a team of study nurses.The ASZ supports and promotes clinical studies with and for infants and children for external and internal sponsors in various therapeutic areas such as oncology, cardiology, pneumology, nephrology, neuropediatrics, orthopaedics and infectious diseases. The full range of activities for executing the approved clinical study protocol can be offered, including planning, implementation, budgeting, coordinating, monitoring and archiving as well as collaboration with all required hospital departments.ResultsUp to now, the ASZ has enrolled around 600 children in clinical trials, with 6 studies completed and 12 studies ongoing. A comprehensive Quality Management system was established and SOPs were jointly created with the adult study center. A digital clinical study request form is available for sponsors via the website.ConclusionWe see an increased demand for pediatric clinical studies across all age ranges and therapeutic areas. We envision a center of excellence with a pool of fully trained study nurses to accommodate and centrally organize all pediatric studies in the UKBB. Parent engagement and patient inclusion is one critical step to further improving healthcare for pediatric patients through highest quality clinical research.Disclosure(s)Nothing to disclose
P106 Impact of a computerised physician order entry system on medication safety in paediatrics
Authors: Wimmer S , Toni I , Trollmann R , Rascher W , Neubert A 
Published: May 2019

BackgroundOne of the most critical steps in the medication process on paediatric wards is the drug prescription.1 Studies have shown that the use of electronic systems may improve the quality of prescribing and reduces medication errors in paediatric inpatients.2This study aims to investigate the impact of a computerised physician order entry (CPOE) system (incl. decision support for dosing) on adverse drug reactions (ADR) and medication errors (ME) in comparison to paper-based prescribing and documentation.MethodsA prospective pre-post study was conducted at a general paediatric ward. All patients aged 17 years or younger that were treated for at least 24 hours during the study periods (5 months pre and post implementation) were observed. Adverse events were identified by intensive chart review.The primary outcome measure was the incidence of clinically relevant ADRs and MEs. Events were assessed regarding causality (WHO), severity (WHO and additionally Dean & Barber for MEs) and preventability (Shumock).3Results338 patients with medication were included in the paper-based prescribing cohort (phase I) and 320 patients with medication in the electronic prescribing cohort (phase II). Median age was 7 (IQR 2 - 14) and 6 (IQR 1 - 13), respectively. In each cohort patients received a median number of 4 different drugs.Potentially harmful MEs were less often observed in the cohort with electronic prescribing (n=231 vs. n=549). The mean number per patient significantly decreased from 1.62 to 0.72 (p< 0.05).During the hospitalisation 2.1% (n=7) patients in phase I and 2.8% (n=9) in phase II experienced clinically relevant ADRs whereof two (0.6%) in each cohort originated from MEs.ConclusionThe implementation of a CPOE system significantly reduces medication errors, particularly those potentially harming patients but has less impact on ADRs.ReferencesFortescue EB, Kaushal R, Landrigan CP, McKenna KJ, Clapp MD, Federico F, et al. Prioritizing strategies for preventing medication errors and adverse drug events in pediatric inpatients. Pediatrics. 2003;111(4Pt 1):722–9.Maaskant JM, Vermeulen H, Apampa B, Fernando B, Ghaleb MA, Neubert A, et al. Interventions for reducing medication errors in children in hospital. The Cochrane database of systematic reviews. 2015;3:Cd006208.Dean BS and Barber ND. A validated, reliable method of scoring the severity of medication errors. Am J Health Syst Pharm 1999;56(1):57–62.Disclosure(s)Nothing to disclose
O18 Therapeutic delivery during breastfeeding: a feasibility study
Authors: Maier T , Peirce P , Baird L , Whitehouse SL , Slater NKH , Beardsall K 
Published: May 2019

BackgroundAt an age when breastfeeding is the optimal nutritional support for infants, enteral drug delivery can be physically and emotionally challenging for parents. Delivery during breastfeeding could serve as an alternative to currently existing approaches. This study aimed to explore its feasibility and acceptability.MethodsVitamin B12 was administered as part of a single-centre feasibility study to breastfed infants at the University of Cambridge Addenbrooke´s Hospital NHS Trust. Hereby a solid formulation (tablet) was placed inside an ultra-thin silicone nipple shield, and worn by a mother during the feed. The study investigated i.) quantitative changes in B12 blood serum levels at baseline and 6–8 hours after the study feed, ii.) mothers’ expectations and experiences via a mixed method approach by a single investigator. Local ethics approval was obtained prior to any study procedures being undertaken (18/LO/0551).ResultsTwenty dyads completed the study protocol. In all cases, no residual tablet was left after the feed, and the tablet’s presence within the shield did not appear to impact feeding. A pharmacokinetic-dependent vitamin B12 increase to 1871 pg/mL (610–4981 pg/mL) from a baseline of 533 pg/mL (236–925 pg/mL) was observed. Mothers described the nipple shield´s surprising ease of use and comfort for delivery, not affecting normal breastfeeding behaviour/sensation, while decreasing infant/maternal distress compared to the use of an oral syringe. All mothers expressed their wish for this approach to become available to parents in the future. Reasoning included the desire (1) of parents to have choices in relation to their infants’ health, (2) to replace a medical intervention with one that was felt to be more ‘natural’.ConclusionsThis study showed that solid formulations can be used for therapeutic delivery whilst breastfeeding and is viewed by mothers as advantageous compared to currently available methods.Disclosure(s)FundingThe research was supported by a WD Armstrong PhD studentship for the Application of Engineering in Medicine, University of Cambridge, the German Academic Scholarship Foundation, and the Kurt Hahn Trust, University of Cambridge. Competing interests (applicable to all authors): None declared.
O37 Use of albendazole in children with asymptomatic toxocariasis
Authors: Garcia Bournissen F , Moroni S , Gonzalez N , Moscatelli G , Ballering G , Altcheh J 
Published: May 2019

BackgroundHuman toxocariasis is highly prevalent and its global importance may be greatly underestimated. Toxocariasis occurs mainly in childhood by ingestion of parasite eggs from contaminated environment. During migration in human tissues the Toxocara larvae can cause several symptoms including eye involvement, but the majority of patients are asymptomatic. Eosinophilia is a marker of activity of this disease. There are no studies supporting the treatment of asymptomatic patients.MethodsTo evaluate the effectiveness of albendazole (10–15 mg/kg/day BID for 15 days) a randomized, placebo-controlled trial was carried out in asymptomatic children (ClinicalTrials.gov #NCT00755560). Treatment response was defined as mean absolute reduction in eosinophil counts, 12 months after treatment.Demographic, complete blood count, liver and renal function and stool parasite exam were assessed at diagnosis, and every 4 months during follow up. Inclusion criteria: age 2 to 15 years, reactive toxocara excretory-secretory substances (TES) by ELISA, eosinophils >1100/mm3, normal fundoscopy and non geohelmintic infection.ResultsThe 45 enrolled subjects, median age 5.3 years (range 2–13), were randomized in a 1: 1 relationship.At 12-month follow-up, eosinophil median was: 1008/mm3 (IQ 25-75680 to 2023) in placebo group and median of 1360/mm3 (IQ 25-75761 to 2226) in albendazole group (p = 0.37).Kinetics of specific antibody titers by the ELISA showed an erratic pattern. No differences were observed in the values between the 2 treatment groups.Both groups had minor adverse events and no patient needed to discontinue medication. In asymptomatic patients with toxocariasis, albendazole was not effective to reduce eosinophil counts.ConclusionGiven that toxocariasis is a neglected disease, in order to evaluate the effectiveness of albendazole or other drugs, further studies need to be conducted.Disclosure(s)Nothing to disclose
P10 Reporting of offspring data in diabetes, HIV infection and hypertension trials during pregnancy: a systematic review
Authors: Aurich B , Martin-Montoya T , Zhang D , Jacqz-Aigrain E 
Published: May 2019

BackgroundAccording to international guidelines clinical trials are conducted during pregnancy to evaluate benefits and risks of medicines for both the mother and her offspring. Consolidated Standards of Reporting Trials (CONSORT) reporting criteria apply to these trials and should include safety data on the offspring. The safety of maternal treatments is a key issue for health care professionals and parents. Diabetes, human immunodeficiency virus (HIV) infection and hypertension are among the most frequent chronic diseases worldwide in women of child bearing potential. The objective of this systematic review was to analyse offspring data reported in clinical trials conducted in pregnant women receiving chronic drug treatment for one of these conditions.MethodsPubmed and Embase (01/01/1997–31/12/2017) were searched for drug trials in pregnant women with diabetes, HIV infection or hypertension. Titles and abstracts were screened, followed by a full text review of eligible articles. Inclusion criteria were interventional clinical trials in pregnant women treated with chronic medication and full text in English. Trial characteristics, maternal and offspring data were extracted. Data was summarised by disease and study. Twelve key items were considered for the offspring. The protocol was registered on PROSPERO (CRD42017057024).ResultsOverall, 196 articles reporting 132 clinical trials (diabetes n=55; HIV n=59; hypertension n=18) were included. The number of births were frequently not reported (diabetes 40%; HIV 24%; hypertension 56%). Congenital malformations were infrequently reported with sufficient detail (diabetes 27%; HIV 34%; hypertension 6%). Similar observations were made for other key items (e.g. foetal losses, neonatal deaths, birth weight corrected for gestational age).ConclusionsUnderreporting of key data for the offspring was frequent in publications of clinical trials in pregnant women with diabetes, HIV infection or hypertension making the assessment of the benefit-risk ratio of treatment options during pregnancy difficult.Disclosure(s)Nothing to disclose
O05 Physiologically based pharmacokinetic modelling to characterize acetaminophen pharmacokinetics and NAPQI formation in non-pregnant and pregnant women
Authors: Mian P , van den Anker JN , van Calsteren K , Annaert P , Tibboel D , Pfister M , Allegaert K , Dallmann A 
Published: May 2019

BackgroundLittle is known about the pharmacokinetics (PK) of acetaminophen during different stages of pregnancy. The aim of this study was to develop a physiologically based pharmacokinetic (PBPK) model to predict acetaminophen PK throughout pregnancy.MethodsPBPK models for acetaminophen and its metabolites were developed in non-pregnant and pregnant women. Physiological and enzymatic changes in pregnant women expected to impact acetaminophen PK were considered. The models were evaluated using goodness-of-fit-plots and through comparison of predicted PK profiles with in-vivo PK data. Predictions were performed to illustrate the concentrations at steady state (Css-mean), used as indicator for efficacy of acetaminophen achieved following 1000 mg q6h. Furthermore, as measurement for potential hepatotoxicity, the molar dose fraction of acetaminophen converted to NAPQI was estimated.ResultsPBPK models successfully predicted the PK of acetaminophen and its metabolites in populations of non-pregnant and pregnant women. Predictions resulted in lowest Css-mean in the third trimester (4.5 mg/L), while Css-mean was 6.7, 5.6 and 4.9 mg/L in non-pregnant, first and second trimester populations, respectively. Assuming a constant increased activity of CYP2E1 throughout pregnancy, the molar dose fraction of acetaminophen converted to NAPQI was highest during the first (11.0%), followed by second (9.0%) and third trimester (8.2%), compared to non-pregnant women (7.1%).ConclusionRisk for drug related hepatotoxicity in pregnant women might be increased as more NAPQI is produced during pregnancy compared to non-pregnant women, especially during the first trimester. However, lack of information on the detoxifying capacity precludes any strong conclusions.Disclosure(s)Paola Mian received a Short term Minor (STM-2017) grant from the Stichting Sophia Kinderziekenhuis fonds to conduct this research.
P13 Serious adverse reactions and off label and unlicensed drug use in children – decade of pharmacovigilance study in Serbia
Authors: Bajcetic M , Joksimovic J 
Published: May 2019

BackgroundOff label (OL) and unlicensed (UL) drug use in children is a widespread global problem. Previous study showed that only 66% of all available drugs for children is with licence in Serbia.1 Data on safety of medicines in children remain lacking, so the key intervention for the effective use of medicine is safety monitoring. Therefore, the aim of this study is to evaluate safety implication of OL and UL drug use in children up to 12 years old.MethodWe conducted a retrospective study based on reports of suspected adverse reactions (ADRs) collected from 2008. to 2018. by Medicines and Medical Devices Agency of Serbia, using the Medical Dictionary for Regulatory Activities and organized by System Organ Class. Sources of information about medicines including vaccines (license, drug formulation, etc.) are the Summary of Product Characteristics and Serbia´s official drug registry.ResultsWithin 10 years, we observed 1595 ADRs. Vaccines, antineoplastic and antimicrobial drugs were the most frequently pharmacotherapeutic subgroups involved. Out of total number of observed ADRs, 433 (28%) were serious; 189 of them led to hospitalization, 31 to life threatening conditions and 7 were fatal. More than a half (63%) of serious ADRs were detected in children for the age group of 28 days - 23 months, followed by the age group of 2 to 11 years (34%) and finally by age group of 0 to 27 days (3%). Serious ADRs were detected in boys (55%) as well as in girls (45%). Out of total number of registered only 3% (46) of ADRs were associated with off-label use; 18 of them were serious, 7 led to life threatening conditions and 3 were fatal.ConclusionThis research provided new insight on the factors such as OL and UL use, that might increase the risk of serious ADRs in children.ReferencesBo&zbreve;i&cacute; B, Stupar S, Stupar D, Babi&cacute; U, Bajčeti&cacute; M. Availability of pediatric-evaluated formulations in Serbia. Indian J Pharmacol 2017 Mar-Apr;49(2):189–193Disclosure(s)Nothing to disclose
P15 Lacosamide monitoring in the serum of children with refractory epilepsy
Authors: Kronenfeld N , Kohn E , Lezinger M , Brandriss N , Heyman E , Bar-Chaim A , Berkovitch M 
Published: May 2019

BackgroundLacosamide is indicated for various types of refractory epilepsy and as adjunctive therapy to other antiepileptic medications. Data on monitoring serum levels of lacosamide in pediatric patients is scarce.ObjectiveTo evaluate the correlation between serum levels of lacosamide and the tolerability in children with refractory epilepsy.MethodsThe medical records of 22 children with refractory epilepsy treated with lacosamide at Assaf Harofeh Medical Center were reviewed. Trough serum levels of lacosamide was measured using HPLC and correlated with its efficacy and safety.ResultsMean age of the children was 11 ± 4 (3–18) years. Median lacosamide daily dose was 9.3 (6.6–11) mg/kg and median plasma concentration was 7.1 (5.9–11.9) ug/ml. The therapeutic range of lacosamide serum concentration is 10 to 20 ug/ml. No change in seizures frequency was reported in 21.4% of children with lacosamide concentrations below 10 ug/ml. However, in 40% of the children, reduction of the seizures frequency was reported when serum concentration was above 10 ug/ml. No serious adverse events were reported during therapy. The prospective part of the study was initiated, and the first patients were recruited.ConclusionLarge studies, preferably prospective, on lacosamide serum monitoring including information on correlation with efficacy and safety are warranted.Disclosure(s)Nothing to disclose
P25 Comparison of renal function estimation methods in critically ill children: a pilot study
Authors: Dhont E , Van Der Heggen T , De Jaeger A , Willems J , De Baere S , Croubels S , Vande Walle J , De Paepe P , De Cock P 
Published: May 2019

BackgroundAccurate assessment of renal function is crucial in intensive care to guide therapy. Both acute kidney injury and augmented renal clearance (ARC) may compromise outcome. Common formulas to estimate glomerular filtration rate (GFR) are unreliable in critically ill adults.1 A comparison of a gold standard technique to assess GFR with these formula-based estimations has never been reported in pediatric intensive care (PICU) patients. Our aim was to evaluate the feasibility of measuring plasma iohexol clearance (CLIOHEX) for GFR assessment in critically ill children and to compare CLIOHEX with estimated GFR using the modified Schwartz formula (eGFRSchwartz).MethodsA prospective, interventional study was conducted at the PICU of the Ghent University Hospital, Belgium. Critically ill children without chronic kidney disease were included. After injection of a weight-dependent bolus of iohexol, serial blood samples (n=6) were taken over a 6-hours interval. CLIOHEX was compared to eGFRSchwartz. Correlation between both methods was assessed by a Pearson´s correlation coefficient (r).Bland-Altman plots were evaluated to assess bias and limits of agreement (LOA). ARC was defined as a GFR exceeding normal values for age plus two standard deviations.Results40 patients, median age 16 months (range 15 days -13,6 years), 72,5% males, were included. No adverse effects related to iohexol were observed. Median CLIOHEX was 121 ml/min/1.73m2 (range: 43–221 ml/min/1.73m2). ARC was present in 20 patients based on CLIOHEX. Median eGFRSchwartz was 81 ml/min/1.73m2 (range: 31–131 ml/min/1.73m2). Only 1 patient was identified with ARC by eGFRSchwartz. eGFRSchwartz was systematically lower than CLIOHEX. There was a good correlation between CLIOHEX and eGFRSchwartz (r = 0,69; p< 0,01). Bias was 34 ml/min/1.73m2 with LOA (-24,5; 93 ml/min/1.73m2)ConclusionCLIOHEX was safely used to measure true GFR in critically ill children. eGFRSchwartz systematically underestimates GFR, especially in patients with ARC and seems not reliable in this patient population.ReferenceBaptista JP, Neves M, Rodrigues L, Teixeira L, Pinho J, Pimentel J ( 2014) Accuracy of the estimation of glomerular filtration rate within a population of critically ill patients. J Nephrol. 27:403–410.Disclosure(s)Nothing to disclose
P37 Reference ranges of blood NT-proBNP in paediatric heart failure and healthy controls: compilation of literature data
Authors: Gangnus T , Suessenbach FK , Makowski N , Burdman I , Laeer S , Burckhardt BB 
Published: May 2019

BackgroundN-terminal pro-brain natriuretic peptide (NT-proBNP) is a valuable biomarker for diagnosis and prognosis of heart failure in adults, included into the European Society Guidelines for heart failure (2016).1 It is also considered as a diagnostic and follow-up marker in paediatric heart failure. The aetiology of paediatric heart failure is heterogeneous and maturation of the cardiac and neurohumoral system influences NT-proBNP levels. Since substantial information is mandatory to enable a long-term follow-up of children with heart failure, the aim was to collect published paediatric NT-proBNP data.MethodsIn January 2019, a literature search using PubMed was performed comprising the following keywords: NT-proBNP, heart failure/dilated cardiomyopathy/congenital heart defect/congenital heart disease/healthy and child/neonate/toddler/infant/paediatric. Eligible publications had to determine levels of NT-proBNP in plasma or serum in paediatric heart failure or healthy children (0–18 years) with the Roche NT-proBNP-immunoassay.ResultsThe search resulted in 343 records, of which 95 measured NT-proBNP in paediatric controls or heart failure. Of them, 48 studies were excluded due to the use of other immunoassays. Following, 47 studies were included into the analysis of which 27 reported NT-proBNP levels in 3435 healthy children and 38 NT-proBNP concentrations in 1885 children with heart failure. The age range of reported levels comprised the day of birth up to 18 years in both groups. The data set revealed that younger children have higher NT-proBNP values than older children and that heart failure patients had increased NT-proBNP levels compared to healthy controls which are also dependent on the severity of disease.ConclusionThe literature search and analysis confirmed that NT-proBNP is an important marker for the detection of heart failure and classification of disease severity in children. Thus, the compiled data set forms a solid data basis for long-term follow-up of a paediatric patient population with heart failure.ReferencesPonikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The task force for the diagnosis and treatment of acute and chronic heart failure of the european society of cardiology (ESC)developed with the special contribution of the heart failure association (HFA) of the esc. Eur Heart J 2016;37(27):2129–200.Disclosure(s)Tanja Gangnus, Fabian K. Suessenbach, Nina Makowski, Ilja Burdman, Stephanie Laeer, Björn B. Burckhardt declare that there is no conflict of interest. The research leading to these results has received funding from the European Union Seventh Framework programme (FP/2007–2013) under grant agreement n°602295 (LENA).