Recently, there has been a remarkable move towards interprofessional collaboration in response to the COVID-19 pandemic and the care of comorbidities. In Germany, there has been a gradual increase in interprofessional learning in medical and pharmacy education, aiming to enhance patient care. To adapt the pharmacy curriculum for collaborative practice between pharmacy and medical students, we developed an immersive interprofessional collaboration course for pharmacy students using adult and pediatric high-fidelity simulators (HFS) to assess and train medication consultation skills. In a randomized controlled trial, we investigated whether interprofessional training between pharmacy and medical students results in differences in pharmacy students’ performance of medication therapy consultation compared to the case of mono-professional training of pharmacy students only. Before and after inter/mono-professional training, each pharmacy student performed an objective structured clinical examination (OSCE) and completed a self-assessment questionnaire. Additionally, an attitude survey towards interprofessional learning was completed by pharmacy and medical students at the end of the training. As expected, interprofessional as well as mono-professional training showed a statistically significant increase in medication consultation skills. Of importance, the performance in the interprofessional training group was significantly better than in the mono-professional group, particularly in drug therapy counselling and consultation behaviors. There was a significant difference between the intervention and control groups in self-assessment scores, and all study participants had positive attitudes toward interprofessional collaboration and training. Therefore, interprofessional training using HFS has been shown to appropriately train pharmacy students for collaborative practice and consultation skills.

Background: Clinical decision support systems (CDSSs) already support community pharmacists in conducting medication reviews (MRs) by identifying important information on interactions and suggesting clinical solutions. However, their impact in terms of quality and time savings is widely unexplored. The aim of our study was to investigate whether MRs are performed faster and better with or without using a CDSS. Methods: In a randomized controlled study with a cross-over design, 71 pharmacists performed a total of four MRs, two with and two without the use of a CDSS. The primary endpoint was defined as the time required for the MRs. The secondary endpoints were the number of predefined relevant drug-related problems (DRPs) detected and pharmacist satisfaction. Results: Without the use of a CDSS, pharmacists needed between 25.7% and 30.7% more time to perform a MR than with a CDSS. In addition, significantly more relevant DRPs were detected in the MRs with CDSS than without CDSS (70% vs. 50%; p = 0.0037). Furthermore, participants stated that they felt more confident using a CDSS for MRs than without. Conclusions: Our results demonstrate that MRs can be performed both faster and better when using a CDSS than without. Consequently, community pharmacists benefit from the use of CDSSs for MRs, as do patients in terms of their drug therapy safety.

Background: Plasma renin activity (PRA) has gained relevance as prognostic marker in adults with heart failure. The use of PRA as a clinically meaningful parameter in children and children with heart failure requires a thorough knowledge of the factors that influence PRA to correctly assess PRA levels. We aim to evaluate the influence of age, heart failure and angiotensin-converting enzyme inhibitor (ACEi) on PRA levels in children. Methods: We conducted a systematic literature search to identify studies on PRA levels in healthy children and in children with heart failure. In addition, we analysed PRA data measured before (n = 35, aged 25 days–2.1 years), 4 hours after (n = 34) and within the first 8 days of enalapril treatment (n = 29) in children with heart failure from the European project Labeling of Enalapril from Neonates up to Adolescents (LENA). Results: Age has a profound effect on PRA levels in healthy children, as PRA levels in the literature are up to about 7 times higher in neonates than in older children. Children with heart failure younger than 6 months showed 3–4 times higher PRA levels than healthy peers in both the literature and the LENA studies. In the LENA studies, the ACEi enalapril significantly increased median predose PRA by a factor of 4.5 in children with heart failure after 4.7 ± 1.6 days of treatment (n = 29, p < 0.01). Prior to treatment with enalapril, LENA subjects with symptomatic heart failure (Ross score ≥3) had a significantly higher PRA than LENA subjects with asymptomatic heart failure of comparable age (Ross score ≤2, p < 0.05). Conclusions: Age, heart failure and ACEi treatment have a notable influence on PRA and must be considered when assessing PRA as a clinically meaningful parameter. Clinical Trial Registration: The trials are registered on the EU Clinical Trials Register (https://www.clinicaltrialsregister.eu). Trial registration numbers: EudraCT 2015-002335-17, EudraCT 2015-002396-18.

Background Enalapril orodispersible minitablets (ODMT) have been authorised by the European Medicines Agency for the treatment of heart failure in children from birth to 17 years of age in 2023. Consequently, the use of enalapril in very young and angiotensin-converting enzyme inhibitor (ACEi) naïve patients is expected to increase. Objectives Simultaneous characterisation of the pharmacokinetics (PK) of enalapril and the active metabolite enalaprilat in ACEi naïve children with heart failure using a combined population pharmacokinetic (PopPK) model and identification of clinically relevant covariates for the dosing of enalapril in this population. Methods Data of ACEi naïve subjects from the European project ‘Labeling of Enalapril from Neonates up to Adolescents’ (LENA) were analysed using nonlinear mixed effects modelling. In the prospective, open-label, multicentre phase II/III PK bridging studies, children with heart failure due to dilated cardiomyopathy (DCM) and congenital heart disease (CHD) received enalapril ODMT according to an age- and weight-dependent dosing regimen. Allometric scaling was implemented for the disposition parameters of enalapril and enalaprilat. Stepwise covariate modelling was used to test the covariates age, sex, serum creatinine and Ross score. The final model was validated using nonparametric bootstrap analysis. Simulations were performed to assess the impact of the covariates after the first dose and at steady state. Results The analysed dataset comprised 173 enalapril and 268 enalaprilat serum concentrations from 34 subjects aged 25 days to 2.1 years (median age = 0.3 years). A combined model consisting of a one-compartment model for enalapril coupled with a one-compartment model for enalaprilat with absorption lag was selected as the structural model. Covariate analysis revealed that the weight-adjusted apparent clearance of enalaprilat increases with increasing age and decreases with increasing serum creatinine. In addition, the weight-adjusted apparent volume of distribution of enalaprilat decreases with increasing Ross score. The simulations indicated that serum creatinine levels above the normal reference range, age and weight were clinically relevant covariates for both the first dose and the steady state dose of enalapril. Furthermore, the simulations indicated that the Ross score is a clinically relevant covariate for the first dose of enalapril. Conclusions The results of the PopPK analysis and simulations indicated that, in addition to the currently considered parameters of weight and renal function, the parameters of age and severity of heart failure should also be considered when dosing enalapril in children with heart failure. Trial Registration Trial registration number (date of registration): EudraCT 2015-002335-17 (30 November 2015), EudraCT 2015-002396-18 (30 November 2015). The trials were registered on the EU Clinical Trials Register (https://www.clinicaltrialsregister.eu).

Background/Objectives: Since 2023, enalapril orodispersible minitablets have been approved in Europe for paediatric heart failure from birth, but no population pharmacodynamic analyses have yet been conducted in this patient group. The objectives were to investigate the effect of the active metabolite enalaprilat on the angiotensin II/angiotensin I ratio in children with heart failure and to determine potential differences compared to healthy adults. Methods: Population pharmacokinetic/pharmacodynamic analysis for healthy adults and population pharmacodynamic analysis for children with heart failure were performed using Monolix. Data were analyzed from 9 healthy adults after a single dose of enalapril and from 27 angiotensin-converting enzyme (ACE) inhibitor-naïve children with heart failure treated with enalapril orodispersible minitablets for up to one year in the ‘Labeling of Enalapril from Neonates up to Adolescents’ (LENA) studies. Results: For the relationship between enalaprilat and the angiotensin II/angiotensin I ratio, a maximum inhibition (I_max) model with full inhibition and sigmoidicity factor was selected for healthy adults and without sigmoidicity factor for children with heart failure. In children with heart failure, the population estimate for the baseline effect was higher (0.19 versus 0.043) and for the half-maximal inhibitory concentration lower (1.19 µg/L versus 30.01 µg/L) than in healthy adults. Four hours after a median initial dose of 0.06 mg/kg enalapril maleate, the angiotensin II/angiotensin I ratio decreased by a median of 79.3% in children with heart failure. Conclusions: Effective ACE inhibition can be assumed at the administered dose in children with heart failure. Population analyses suggest that children with heart failure may be more sensitive to enalaprilat than healthy adults.