bluuebunny/crossref_metadata_2025_split huggingface dataset:
13 Feasibility of the pragmatic PBPK modelling approach – towards model-informed dosing in paediatric clinical care
Authors: van der Heijden Joyce , Freriksen Jolien , de Hoop-Sommen Marika , Greupink Rick , de Wildt Saskia 
Published: May 2023

IntroductionMore than half of all drugs are still prescribed off-label to children. To support off-label dosing, pharmacokinetic (PK) data are needed. Physiologically-based pharmacokinetic (PBPK) models are increasingly used to study PK and guide dosing decisions. We hypothesize that combining existing compound models with a paediatric population model can be used to pragmatically predict paediatric exposure.MethodsSeven drugs, with various pharmacokinetic characteristics, were selected (i.e. meropenem, ceftazidime, azithromycin, propofol, midazolam, lorazepam, and caffeine). Simcyp v20 was used to predict exposure in adults, paediatrics and preterm neonates by combining an existing compound file with various virtual populations. Predictive performance was evaluated by calculating the ratio of predicted-to-observed PK parameter values (0.5 to 2-fold acceptance range) and by a visual predictive check.ResultsOverall, model predictions in adults were able to capture clinical observed PK data and confidence in PBPK model performance for predicting PK in this population was therefore considered high. However, predictive performance decreased when predicting PK in the paediatric population, even more so in preterm neonates.ConclusionsPragmatic PBPK modelling in paediatrics is feasible, though the approach is not straight forward as limitations, such as inadequate parameterization with respect to paediatric-specific ADME properties, have been observed. A thorough understanding of the models assumptions and limitations is required, before dose recommendations can be generated for use in clinical practice.This abstract is based on research funded by the Bill & Melinda Gates Foundation.
14 A comparison of age-banded and weight-based oral paracetamol dosing in hospitalised children
Authors: Wright Kirstie , Craske Jennie , Gill Andrea , Jenson John , Arnold Philip 
Published: May 2023

The British National Formulary for Children contains two dosing strategies for oral paracetamol: age-banded and weight-based. Weight-based is used in our hospital. This study compares dosing strategies in inpatients.Retrospective analysis over 4 years was undertaken in a single tertiary paediatric hospital. Data was collected from electronic patient records. Patients 3 months to 18 years were included. One measurement per admission was allowed. This was compared the Health Survey England (HSE) and National Child Measurement Programme (NCMP).Of 161150 admissions it was possible to match weight to 115466 (58287 patients) and height to 18806 (4892 patients). Of 95598 paracetamol prescriptions, doses <10mg/kg occurred in 5427(5.7%) prescriptions and doses >20mg/kg in 691(0.72%) prescriptions. Of the doses <10mg/kg, 1003 were in patients >66.7kg. Applying age-banded doses to all admissions would result in doses <10mg/kg in 20748 (18%) of admissions (13111 patients) and doses >20 mg/kg would occur in 4420 (3.8%) of admissions (2054 patients), most commonly in teenagers. Weight-based dosing (maximum 1g/dose) would lead to doses <10mg/kg in 931 admissions (395 patients).The potential for inadequate or excessive paracetamol dosing is greater with age-banded doses compared with weight-based doses in hospitalised children. Compared to NCMP and HSE data, obesity is more common in hospitalised children across all ages. Compared to NCMP data, underweight is more common in reception aged hospitalised children but not in year 6. Therefore, atypical body weights are more common in hospitalised children than the general population. A higher proportion of low body weight is seen in young children and teenagers. As a result, age-banded dosing should not be used in hospitalised children
18 In vitro investigation of vancomycin-induced kidney injury: development of a 2D cellular model
Authors: Rhodes Lawrence , McWilliam Stephen , Chadwick Amy 
Published: May 2023

IntroductionVancomycin is a glycopeptide antibiotic that targets gram-positive bacteria and is the recommended treatment against MRSA infections. However, it is known to cause kidney injury in children. Vancomycin accumulates in proximal tubule cells but relatively little is known regarding the mechanism of this. We conducted a multiparameter assessment of vancomycin toxicity in a novel human renal cell line, Conditionally immortalised proximal tubule epithelial cells (ciPTECs), to determine if these cells recapitulate vancomycin-induced kidney injury (VIKI) in vitro.MethodsThree ciPTEC lines were used (parent ciPTEC, and ciPTECs with upregulated expression of organic anion transporters 1 (ciPTEC OAT1) or 3 (ciPTEC OAT3), to assess the respective involvement of these transporters in vancomycin accumulation. ciPTECs were cultured at 33°c and seeded in 96-well plates at 1x104 cells/well. Vancomycin stocks were prepared in distilled water and administered between 1mM and 10mM for 24hr incubations before cell viability (ATP) and cell cytotoxicity (LDH) assays were performed.ResultsATP data showed a dose-dependent increase in vancomycin toxicity with 17% cell viability observed at10mM. (EC50=5.6mM) Membrane permeabilization was only observed at 10mM (60% LDH retention), with no change observed at lower concentrations administered. There was no difference in vancomycin toxicity observed between each cell type.ConclusionsOur results suggest that ciPTECs recapitulate the nephrotoxicity induced by vancomycin and indicates that OATs are not involved in vancomycin uptake. Here, we established a proof of concept for the use of ciPTECs as a 2D cellular model for VIKI as toxicity was observed after vancomycin administration.
23 Plasma renin activity in young children with heart failure: influence of age, disease and ACE inhibitor treatment
Authors: Steichert Melina , Cawello Willi , Breur Johannes MPJ , Male Christoph , de Wildt Saskia N , Läer Stephanie 
Published: May 2023

IntroductionIncreased plasma renin activity (PRA) levels may have various causes: PRA has gained importance as prognostic marker for patients with heart failure; age may have an influence on endogenous PRA levels; and ACE inhibitor (ACEi) treatment can also interfere with PRA levels. We aimed to investigate PRA levels in very young children with heart failure, with and without ACEi treatment.MethodsAs part of a PK-PD study of enalapril for pediatric heart failure (LENA studies), blood samples were collected and analyzed for PRA levels before, 4 hours after and within the first week of enalapril treatment. In addition, a literature search was conducted according to the PRISMA concept in MEDLINE to identify studies on PRA levels in healthy children as well as in children with heart failure in the age range from 1 day up to 2 years. Comparison was performed with LENA study data and with data from 9 healthy volunteers.ResultsInfants from LENA studies with heart failure (n= 35, aged 25 days – 2.1 years) had median PRA levels of 19.7 (n=35) before, 29.0 (n=34, p>0.05) 4 hours after enalapril dose, and 89.1 ng/mL/h (n=29, p<0.01) after 5 days of treatment. Literature search revealed mean PRA levels in healthy children between 2.3 to 29.8 (n= 14 studies) and 10.0 to 87.1 ng/mL/h in ACEi naïve heart failure children (n= 4 studies). PRA levels of 9 healthy adults ranged between 0.13 to 1.85 ng/mL/h.ConclusionsVery young children had higher endogenous PRA levels compared to adults. Heart failure at this age was associated with even higher PRA levels and ACEi treatment further increased PRA levels. These results indicate that patients appear to respond to ACEi treatment but question the value of PRA levels as prognostic marker in this population.
24 Antipsychotics use and weight gain in children compared to adults: analysis of spontaneous adverse drug reaction reports
Authors: Kaguelidou Florentia , Lieber Zaba , Montastruc Francois , Durrieu Genevieve , Treluyer Jean-Marc , Chouchana Laurent 
Published: May 2023

IntroductionWeight gain and obesity are common adverse effects of antipsychotics (APs). We aimed to assess AP-induced weight gain in pediatrics compared to adults.MethodsIn a case-non case study using the WHO global database of individual case safety reports (ICSRs), VigiBase®, we evaluated the existence of disproportionality in weight gain reporting under antipsychotic treatment in children and adolescents compared to adults. Disproportionality of weight gain reporting was evaluated using the reporting odds ratio (ROR) with corresponding 95% confidence intervals (95%CI). Analysis was adjusted for sex, reporting country, year of notification, reporter qualification and concomitant use of antidepressants (ADs) and lithium.ResultsA total of 282,224 ICSRs reported with an AP were retrieved: 6,446 (2.3%) in children, 14,112 (5%) in adolescents and 261,666 (92.7%) in adults. In children, 1,544 (24%) of ICSRs reported weight gain, 1,831 (13%) in adolescents and 13,506 (5.6%) in adults. Most weight gain cases concerned male patients (55%) and were reported by health professionals (47%) in North America (54%) and Europe (27%). Concomitant use of ADs and lithium was reported in 36% and 3.5% of weight gain cases overall. Disproportionality of weight gain reporting associated with APs was found in adolescents (adjusted ROR: 2.3 [95%CI 2.1–2.4]) and in children (aROR: 3.6 [95%CI 3.3–3.8]) compared to adults. Use of risperidone was associated with the highest increase in weight gain reporting in children (aROR 4.9, 95%CI 3.9–6.1) and adolescents (aROR 3.6, 95%CI 3.1–4.1).ConclusionsChildren and adolescents are at higher risk of reporting weight gain under APs than adults.
25 Point prevalence study of paediatric polypharmacy
Authors: Moss James , Rashed Asia , Jensen John , Wilson John , Walker Lauren , Hawcutt Daniel 
Published: May 2023

IntroductionPaediatric polypharmacy is defined as two or more medicines, which is lower than the definition in adults (>5 medicines). A recent scoping review of paediatric polypharmacy found a mean prevalence of 39.7% with a large range from 0.9% to 98.4%.MethodsPrescribing data from 85 active practices across Liverpool Clinical Commissioning Group (CCG), was extracted on the 6th January 2021 to include all patients below 18 years of age. Prescribing data was also obtained for Alder Hey Children’s Hospital from the electronic prescribing system, Meditech on the 12th January 2021. Descriptive analysis was performed.ResultsOf the 110,097 CYP registered in primary care, 17,271 (16%) were prescribed >2 medications, 3,507 (3·2%) >5, 715 (0·7%) ≥10, and 202 (0·2%) ≥15. The median number of CYP prescribed ≥10 and ≥15 medications per primary care practice was 7 (range 0–34) and 2 (range 0–11), respectively.Within Alder Hey Children’s Hospital, 139 inpatients were identified, with 126 patients (91%) prescribed two or more medicines. The most frequently prescribed medicine was paracetamol. When ‘as required’ and ‘one off’ medicines were removed, omeprazole was the most frequently prescribed medicine.ConclusionsMany children within Liverpool CCG meet the definition for paediatric polypharmacy. Further research is required to assess the consequences of paediatric polypharmacy and address its management which is under recognised and underrepresented in the literature to date.
27 Risk factors of augmented renal clearance in critically ill children using iohexol clearance for renal function assessment
Authors: Dhont Evelyn , Heggen Tatjana Van Der , Snauwaert Evelien , Willems Jef , Walle Johan Vande , de Cock Pieter 
Published: May 2023

IntroductionAugmented renal clearance(ARC) of hydrophilic drugs is frequent in PICU patients and warrants adjustment of standard dosing regimens to prevent therapeutic failure. Knowledge of patient-, disease- and therapy-related factors associated with ARC, would allow to predict before the start of treatment, which patients would benefit from higher drug doses. We aimed to identify predictors of ARC in critically ill children with normal serum creatinine(Scr) using iohexol plasma clearance (CLiohexol) to quantify renal function.MethodsWe performed a post hoc analysis of data collected from an interventional study conducted at our academic PICU, which measured glomerular filtration rate (GFR) by CLiohexol in patients with normal Scr. ARC was defined as GFR exceeding normal values for age plus 2 standard deviations. Multivariable logistic regression analysis was performed to identify predictors of ARC.ResultsGFR was measured in 85 patients, median age was 16 [IQR 5;89] months, 59% had a surgical profile. Median CLiohexol was 122[IQR 75;152] ml/min/1.73m2. Fourthy patients out of 85 (47%) expressed ARC. Postoperative status was identified as independent predictor of ARC (p=0.014, OR 4.253, 95%CI 1.338–13.517). However, in patients after cardiac surgery the odds of developing ARC were significantly lower (p=0.010, OR 0.163, 95%CI 0.041 –0.644). There was a trend suggesting more ARC in male patients and in those without need for vaso-active drugs, however, this was not statistically significant.ConclusionOur findings raise clinicians’ awareness about ARC potentially being present in children after major surgery. This knowledge allows to anticipate on enhanced elimination of drugs by using empirically adjusted dosing regimens immediately from the start of treatment.
29 What domains related to medicines were measured in studies of burden of care for paediatric patients? A systematic review
Authors: Thatparan Tharshiya , Marro Julien , Hawcutt Daniel 
Published: May 2023

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.
30 Utilization of and barriers to individual treatment trials in mucopolysaccharidosis – interim results of an expert survey
Authors: Wiesinger Anna-Maria , Lagler Florian , Scarpa Maurizio , Giugliani Roberto , Lampe Christina , Kampmann Christoph 
Published: May 2023

IntroductionMucopolysaccharidoses (MPS), comprise a group of rare chronically debilitating metabolic diseases and associated with reduced life expectancy and a substantial unmet clinical need. Current research directs towards a number of new treatment targets and strategies. Individual treatment trials (ITT) could make these options rapidly available to patients. Based on scientific publication, this is hardly used. We assess the utilization of and relevant barriers to ITT in MPS as well as potential solutions.MethodsPhase 1 was done with 5 international top experts. After this interim analysis, the survey will be rolled out to a broader group of experts.ResultsFive MPS experts from Austria, Brazil, Germany and Italy have been enrolled. In total these clinicians manage about 350 MPS patients. Only three experts ever ran 1–3 numbers of ITT in MPS patients, solely MPS type II (n=2) and VI (n=1), summing up to a total of five ITTs, which is about 1.4% of their patients. The treatments used in ITTs comprise Montelukast, THC, Curcuma and a viral vector with transgene. As barriers for a wider use of ITTs, the im-practicability for implementation (n=1) and the insufficient training in ITT (n=1) have been indicated. All experts consider it highly likely that a decision analysis tool increases the use of ITT in MPS.ConclusionsITT are used in about 1% of MPS patients. This seems extremely low, considering the commonness of off label use in children with severe conditions, the high unmet medical need in MPS and the number of research results, which indicate various promising repurposing strategies. This interim analysis already demonstrates several relevant barriers and high potential of the planned decision framework tool to overcome this.
34 Attitudes of children and young people and their parents towards polypharmacy – pilot study
Authors: Moss James , Rashed Asia , Walker Lauren , Hawcutt Daniel 
Published: May 2023

IntroductionA recent survey of healthcare professionals found that healthcare professionals concerns about patient and family anxiety was the main barrier to deprescribing. However, the attitudes of families, children and young people (CYP) have not previously been sought.MethodsA questionnaire was designed to assess the attitudes of CYP and their parents towards polypharmacy and deprescribing based on a previously validated adult questionnaire (rPATD). Initial review and modification took place following input from a young person patient and public involvement group and a content evaluation panel of experts. Ethics approval was obtained, and a maximum of 22 participants (10% of the total study population) were to be recruited for the pilot. Inclusion criteria were CYP taking >2 for 28 days or more. The questionnaire was completed online using Microsoft Forms. Descriptive analysis was undertaken.ResultsTwenty participants completed the piloting process (12 parents, 5 CYP aged 10–15 years and 3 CYP aged 16–17 years), as saturation was achieved. The mean number of medicines taken was six. Most parents (67%) thought their children were taking many medicines, whereas only 38% of CYP agreed with this. Only one CYP in the 10–15yrs stated they wanted to be involved in decisions about their medicines, whereas all of the CYP in the 16–17yrs cohort, and 92% of parents, said they liked to be involved. Overall, 83% of parents and 63% of CYP stated they would like to try stopping one of their medicines if it was advised by a doctor.ConclusionsThe pilot data would suggest that CYP and their parents would be happy to consider stopping one of their medicines if advised to do so but data from the full study, which is currently recruiting, and statistically powered is awaited.
38 Innovative high-fidelity simulation for vaccination training of pharmacist including emergency cases - a randomised controlled study
Authors: Sayyed Shahzad , Reda Sharkas Ahmed , Ali Sherazi Bushra , Dabidian Armin , Schwender Holger , Läer Stephanie 
Published: May 2023

IntroductionRecently, pharmacists in Germany were allowed to administer influenza and COVID-19 vaccines for people aged 12 years and older in order to increase vaccination coverage rates. To adapt pharmacy curriculum for clinical practice, an innovative, high level vaccination training course comprising clinical skills, techniques required for level of competence was developed with participants interacting either with a high-fidelity simulator or low-fidelity injection pad. Clinical scenarios to manage adverse events were also implemented.MethodsA randomized controlled trial using a pre-post-design with pharmacy undergraduates alongside with a theoretical part was performed. The intervention group interacted with a high-fidelity simulator, while the control group was trained with low-fidelity injection pads. Before and after the respective training each participant went through an objective structured clinical examination (OSCE) and each participant completed a self-assessment questionnaire and knowledge quiz.ResultsOSCE Score were raised through an analytical checklist examining skills in anamnesis, patient information, vaccination process, and handling emergency case. Both training methods showed a significant (p<0,01) increase of skills but a significant (p<0,01) greater increase in the intervention group compared to the control group, particularly in vaccination process (p=0,007). Both Groups showed a similar increase of self-assessment score raised through a 6-point-Likert scale, and no significant differences were observed in the quizzes.ConclusionsHigh fidelity simulation proves to be an appropriate tool to train pharmacy students for vaccine administration, as a new pharmaceutical service and enable the students to recognize and manage adverse events.
Increasing uptake of FIT colorectal screening: protocol for the TEMPO randomised controlled trial testing a suggested deadline and a planning tool
Authors: Robb Kathyrn A , Kotzur Marie , Young Ben , McCowan Colin , Hollands Gareth J , Irvine Audrey , Macdonald Sara , McConnachie Alex , O'Carroll Ronan E , O'Connor Rory C , Steele Robert J C 
Published: May 2023

IntroductionScreening can reduce deaths from colorectal cancer (CRC). Despite high levels of public enthusiasm, participation rates in population CRC screening programmes internationally remain persistently below target levels. Simple behavioural interventions such as completion goals and planning tools may support participation among those inclined to be screened but who fail to act on their intentions. This study aims to evaluate the impact of: (a) a suggested deadline for return of the test; (b) a planning tool and (c) the combination of a deadline and planning tool on return of faecal immunochemical tests (FITs) for CRC screening.Methods and analysisA randomised controlled trial of 40 000 adults invited to participate in the Scottish Bowel Screening Programme will assess the individual and combined impact of the interventions. Trial delivery will be integrated into the existing CRC screening process. The Scottish Bowel Screening Programme mails FITs to people aged 50–74 with brief instructions for completion and return. Participants will be randomised to one of eight groups: (1) no intervention; (2) suggested deadline (1 week); (3) suggested deadline (2 weeks); (4) suggested deadline (4 weeks); (5) planning tool; (6) planning tool plus suggested deadline (1 week); (7) planning tool plus suggested deadline (2 weeks); (8) planning tool plus suggested deadline (4 weeks). The primary outcome is return of the correctly completed FIT at 3 months. To understand the cognitive and behavioural mechanisms and to explore the acceptability of both interventions, we will survey (n=2000) and interview (n=40) a subgroup of trial participants.Ethics and disseminationThe study has been approved by the National Health Service South Central—Hampshire B Research Ethics Committee (ref. 19/SC/0369). The findings will be disseminated through conference presentations and publication in peer-reviewed journals. Participants can request a summary of the results.Trial registration numberclinicaltrials.govNCT05408169