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Background A significant proportion of patients and informal caregivers favor an active role in decisions concerning their health. Simultaneously, governments aim to shift treatment from a professional care setting to a community setting, in light of an ageing population, a decreasing number of health workers and allocation of scarce resources. This transition of care solicits patients’ and informal caregivers’ ability to self-manage. Therefore, the Maastricht University Medical Centre + has established the Academy for Patients and Informal caregivers. The aim is to proactively and professionally support patients and their informal caregivers to enhance their self-management. For that, the Academy offers activities in three categories: (1) instruction of nursing techniques, (2) training of e-health competencies and (3) the provision of self-management programs. Both patients with an episodic care need, as well as patients and informal caregivers with chronic illness, are eligible to participate in the Academy’s activities. However, little is known about the experience of these interventions from the perspective of patients, informal caregivers and healthcare professionals. Methods We conducted semi-structured interviews with 15 patients, 8 informal caregivers and 19 health care professionals who either participated in, referred to or received patients from the Academy. Topics revolved around self-management and the Quadruple aim, covering topics such as patient experiences, healthcare costs, health and well-being of the population and improving work life for health professionals. Data were analyzed using thematic analysis. Results Patients and caregivers experienced an increase in the ability to manage health needs independently, leading to increased mental well-being and self-efficacy. They felt recognized as partners in care, although managing illness needs came with its own burdens. Health care professionals indicated that they felt assured of the quality, uniformity and availability of activities due to its central organization, with instruction nurses finding greater meaning in their work. On the level of health care systems, participants in this study mentioned a decrease in use of formal healthcare, whilst enabling a more equitable division of care. Conclusion Stakeholders’ experiences with the Academy for Patients and Informal caregivers indicate that participation contributes to development of self-management, whilst also improving working conditions, reducing the appeal to formal care and advancing equity in healthcare. The burden for patients and informal caregivers is to be considered in future developments.

Therapeutic hypothermia (TH) is standard treatment for neonates (≥36 weeks) with perinatal asphyxia (PA) and hypoxic-ischemic encephalopathy. TH reduces mortality and neurodevelopmental disability due to reduced metabolic rate and decreased neuronal apoptosis. Since both hypothermia and PA influence physiology, they are expected to alter pharmacokinetics (PK). Tools for personalized dosing in this setting are lacking. A neonatal hypothermia physiology-based PK (PBPK) framework would enable precision dosing in the clinic. In this literature review, the stepwise approach, benefits and challenges to develop such a PBPK framework are covered. It hereby contributes to explore the impact of non-maturational PK covariates. First, the current evidence as well as knowledge gaps on the impact of PA and TH on drug absorption, distribution, metabolism and excretion in neonates is summarized. While reduced renal drug elimination is well-documented in neonates with PA undergoing hypothermia, knowledge of the impact on drug metabolism is limited. Second, a multidisciplinary approach to develop a neonatal hypothermia PBPK framework is presented. Insights on the effect of hypothermia on hepatic drug elimination can partly be generated from (human/animal) profiling of hepatic drug metabolizing enzymes and transporters. Also, endogenous biomarkers may be evaluated as surrogate for metabolic activity. To distinguish the impact of PA hypothermia on drug metabolism, neonatal animal data are needed. The conventional pig is a well-established model for PA and the neonatal Göttingen minipig should be further explored for PA under hypothermia conditions, as it is the most commonly used pig strain in nonclinical drug development. Finally, a strategy is proposed for establishing and fine-tuning compound-specific PBPK models for this application. Besides improvement of clinical exposure predictions of drugs used during hypothermia, the developed PBPK models can be applied in drug development. Add-on pharmacotherapies to further improve outcome in neonates undergoing hypothermia are under investigation, all in need for dosing guidance. Furthermore, the hypothermia PBPK framework can be used to develop temperature-driven PBPK models for other populations or indications. The applicability of the proposed workflow and the challenges in the development of the PBPK framework are illustrated for midazolam as model drug.

Vancomycin pharmacokinetic (PK) and pharmacodynamic (PD) data in neonates are based on total concentrations. However, only unbound vancomycin is pharmacologically active. The objective was to determine vancomycin protein binding and the covariates impacting unbound vancomycin concentration in neonates and young infants. In neonates and young infants to whom vancomycin was administered intermittently for medical indications, total and unbound vancomycin plasma concentrations were determined using LC-MS/MS. Sampling occurred randomly during vancomycin exposure, covering a broad range of concentrations. Impact of covariates on unbound vancomycin concentration was determined using linear regression. Significant results of the univariate regressions were entered in a stepwise multiple regression. Passing-Bablok regression and Bland-Altman were used to assess the difference between measured and calculated unbound vancomycin concentration. Thirty-seven samples in 33 patients (median (interquartile range) gestational age 35 (29–39) weeks) were collected. Median total and unbound vancomycin concentrations were 14.2 (7.4–20.6) and 13.6 (7.2–22.5) mg/L, respectively. Median unbound fraction was 0.90 (0.77–0.98). Multiple regression revealed total vancomycin concentration (β = 0.884, p < 0.001) and albumin (β = − 0.323, p = 0.007) as most important covariates of unbound vancomycin concentrations, with an R2 adjusted of 0.953 (p < 0.0001). Mean absolute difference between calculated and measured unbound vancomycin was − 0.008 (95% CI − 0.92–0.91) mg/L. The unbound vancomycin fraction in neonates is higher compared to that in children and adults, and total vancomycin concentration and albumin were the most important covariates of unbound vancomycin concentration. Integration of protein binding in future PK/PD analyses is appropriate to optimize vancomycin dosing and to determine population-specific vancomycin PD targets for neonates.

This study focused on comparing broiler meat quality across different production systems and seasons. Chicken carcasses from intensive, free-range, and dual-purpose poultry systems were analyzed for intrinsic and extrinsic quality traits. The results revealed significant effects of the production system and season. Carcasses from dual-purpose and intensive systems were heavier. Greater carcass weight was recorded in autumn and winter. The mean post-mortem pH of breast and thigh was lower in extensive and dual-purpose systems and significantly lower in winter and spring. Colorimetric parameters varied by system, as higher means of redness (intensive), yellowness (free-range), and lightness (dual-purpose) were observed. Meat from intensive systems was less firm, showed higher levels of unsaturated fatty acids and better oxidation stability. Dual-purpose displayed higher levels of polyunsaturated fatty acids. The interaction effect was significant for most quality parameters.

The aim of this study was the evaluation of egg quality between three different farming systems. Eggs collected from intensive (IS), extensive (ES), and dual-purpose systems (DPSs) at three stages of the production cycle (age) were analyzed for both external and internal traits. ISs represent high-input systems while ESs and DPSs represent low-input systems. Both the farming system and age had significant effects on quality characteristics. Eggs from the ES displayed a greater egg weight (64.3 ± 0.20 g) and shell weight (6.6 ± 0.03 g). Eggs from the IS farms displayed a higher Haugh unit score (83.2 ± 0.50), darker colored yolks (12.0 ± 0.06), and a lower incidence of blood spots (0.2 ± 0.05). The age and farming system influenced the fatty acid profile of eggs across farming systems. In particular, DPS eggs showed higher levels of unsaturated (62.2 ± 0.20%) and lower levels of saturated (37.8 ± 0.10%) fatty acids. The effect of age was also significant on the oxidation stability of yolks. The interaction effect (farming system × age) had significant effects on most traits. However, the farming system alone accounted for a greater portion of the variation in most egg quality parameters.

This commentary further reflects on the paper of De Sutter et al. on predicting volume of distribution in neonates, and the performance of physiologically based pharmacokinetic models We hereby stressed the add on value to collaborate on real world data to further close this knowledge gap. We illustrated this by weight distribution characteristics in breastfed (physiology) and in asphyxiated (pathophysiology), with additional reflection on their kidney and liver function.

BackgroundCharacterizing the dynamics of serum creatinine concentrations (Scr) and associated creatinine clearance (CLcr) as a measure of kidney function in extremely low birth weight (≤ 1000 g; ELBW) neonates remains challenging.MethodsWe performed a retrospective study that included longitudinal Scr (enzymatic assay) data from 148 ELBW neonates up to 6 weeks after birth. Change of Scr and inter-individual variability was characterized with nonlinear mixed-effect modeling. Key covariates such as gestational age (GA), mode of delivery (MOD), and treatment with ibuprofen or inotropic agents were investigated.ResultsA total of 2814 Scr concentrations were analyzed. GA was associated with Scr at birth (higher with advancing GA), and GA and MOD showed an association with postnatal maturation of CLcr (faster clearance increase with advancing GA and after C-section). Small CLcr decrease (≤ 5%) was quantified during ibuprofen treatment. For a GA of 27 weeks, mean Scr (estimated CLcr) at birth was 0.61 mg/dl (0.23 ml/min), increasing to 0.87 mg/dl (0.27 ml/min) at day three, and decreasing to 0.36 mg/dl (0.67 ml/min) at day 42 after birth.ConclusionsWe report the first mathematical model able to characterize Scr and CLcr in ELBW neonates during the first 6 weeks of life in a quantitative manner as a function of GA, MOD, and ibuprofen treatment. This model allows the derivation of GA-adjusted reference ranges for ELBW neonates and provides a rationale for normative Scr concentrations, and as such will help clinicians to further optimize monitoring and treatment decisions in this vulnerable patient population.

Background Perinatal mental health (PMH) problems are common, in particular among perinatal women from migrant backgrounds. Despite global recommendations for universal screening, implementation remains inconsistent and inequitable. To better understand these inequities, this study aimed to explore healthcare providers’ experiences and needs regarding screening and referral for perinatal depression and anxiety among women from migrant backgrounds in Flanders, Belgium. Methods A qualitative study design was employed, conducting focus groups with primary care and community-based healthcare providers. Participants were recruited through a purposive sampling strategy using newsletters, social media, and email. Discussions were recorded, verbatim transcribed, and analysed using inductive framework analysis. To ensure credibility, a member check survey was conducted. Results Based on the analysis of five heterogeneous focus groups ( n = 20 in total), four themes and seven subthemes were identified: (1) complexity of interactions between healthcare providers and migrant women: underscoring (a) the impact of cultural and language barriers and (b) the importance of a trusting relationship; (2) screening in its context: highlighting (c) the ambivalence around screening and (d) the impact of organisational and financial factors on implementation; (3) accessible referral: stressing (e) the importance of person-centred, culturally and linguistically appropriate services; and (4) PMH in its proper context: addressing (f) the role of stigma, taboo, PMH literacy, and understanding, and (g) the involvement of women’s partner, family and broader network. Conclusions These findings underscore the complexity of screening and referral practices among all (expectant) mothers, particularly among women from migrant communities, and simultaneously offer a foundation to develop and implement screening and referral protocols. Ideally, these protocols should be co-designed with perinatal service users to ensure equitable practices for all.

Therapeutic hypothermia (TH) significantly reduces mortality and morbidities in neonates with Neonatal Encephalopathy (NE). NE may result in neonatal death and multisystem organ impairment, including acute kidney injury (AKI). Our study aimed to utilize machine learning (ML) methods to predict the outcome of TH-treated NE neonates developing AKI and death during TH. In this retrospective multinational study, 1149 TH-treated NE neonates and 801 controls were included. AKI was classified using KDIGO neonatal criteria based on serum creatinine measurements. The ML model incorporated gestational age, birth weight, postnatal age, and serum creatinine values. The algorithm used all these covariates to predict one of five outcomes: survival with/without AKI, mortality with/without AKI, and hospitalized non-NE controls. The XGBoost model achieved an AUC of 95% and an accuracy of 75.08% in predicting AKI and survival, surpassing other ML classifiers that demonstrated accuracy levels ranging from 54% to 65%. To our knowledge this is the first ML model trained on multicenter, multinational data specifically aimed at predicting neonates’ AKI, death, and survival within the first three days. Our ML scoring systems’ code and user interface are freely available ( https://github.com/NUBagciLab/Therapeutic-Hypothermia-Outcome-Classification , https://thprediction.streamlit.app/ ). This tool has potential to support neonatologists to personalize therapies, and to optimize pharmacotherapy for renally cleared drugs.

Physiologically based pharmacokinetic (PBPK) modelling is a bottom-up approach to predict pharmacokinetics in specific populations based on population-specific and medicine-specific data. Using an illustrative approach, this review aims to highlight the challenges of incorporating physiological data to develop postpartum, lactating women and breastfed infant PBPK models. For instance, most women retain pregnancy weight during the postpartum period, especially after excessive gestational weight gain, while breastfeeding might be associated with lower postpartum weight retention and long-term weight control. Based on a structured search, an equation for human milk intake reported the maximum intake of 153 mL/kg/day in exclusively breastfed infants at 20 days, which correlates with a high risk for medicine reactions at 2–4 weeks in breastfed infants. Furthermore, the changing composition of human milk and its enzymatic activities could affect pharmacokinetics in breastfed infants. Growth in breastfed infants is slower and gastric emptying faster than in formula-fed infants, while a slower maturation of specific metabolizing enzymes in breastfed infants has been described. The currently available PBPK models for these populations lack structured systematic acquisition of population-specific data. Future directions include systematic searches to fully identify physiological data. Following data integration as mathematical equations, this holds the promise to improve postpartum, lactation and infant PBPK models.