Drug Safety During Breastfeeding: A Comparative Analysis of FDA Adverse Event Reports and LactMed.

Background/objectives: While breastfeeding is highly recommended, breastfed infants may be exposed to drugs by milk due to maternal pharmacotherapy, resulting in a risk of adverse drug events (ADE) or reactions (ADRs). The U.S.

Unbound Ceftriaxone Concentrations in Plasma Measured Using Ultrafiltration Versus Equilibrium Dialysis: A Short Communication.

Background: Ceftriaxone is a first-line beta-lactam antibiotic used in diverse clinical settings. Owing to pharmacokinetic alterations, ceftriaxone therapeutic drug monitoring is currently recommended for patients in the intensive care unit. Ultrafiltration is typically used to measure unbound ceftriaxone concentrations, as it is less costly and time-consuming compared with equilibrium dialysis.

Tracking the journey: Gastrointestinal transit and intraluminal pH dynamics in aging populations using wireless motility capsule.

Introduction: Gastrointestinal (GI) changes may alter drug absorption, potentially impacting both efficacy and safety of oral pharmacotherapy. However, the GI physiology is rarely studied in the aging population. This study aimed to explore GI transit time and pH in geriatric inpatients and older adults, and compare these findings with those from young volunteers.

A Prediction Model to Identify Clinically Relevant Medication Discrepancies at the Emergency Department (MED-REC Predictor): Development and Validation Study.

Background: Many patients do not receive a comprehensive medication reconciliation, mostly owing to limited resources. We hence need an approach to identify those patients at the emergency department (ED) who are at increased risk for clinically relevant discrepancies.

Objective: The aim of our study was to develop and externally validate a prediction model to identify patients at risk for at least 1 clinically relevant medication discrepancy upon ED presentation.

Development and Characterization of a Human Mammary Epithelial Cell Culture Model for the Blood-Milk Barrier-A Contribution from the ConcePTION Project.

It is currently impossible to perform an evidence-based risk assessment for medication use during breastfeeding. The ConcePTION project aims to provide information about the use of medicines during lactation. The study aimed to develop and characterize an in vitro model of the blood-milk barrier to determine the extent of the milk transfer of xenobiotics, relying on either on human mammary epithelial cells (hMECs) or immortalized cell lines derived from breast tissue.

The Impact of Customized Screening Intervals on the Burden of Drug-Drug Interaction Alerts: An Interrupted Time Series Analysis.

Fixed and broad screening intervals for drug-drug interaction (DDI) alerts lead to false positive alerts, thereby contributing to alert fatigue among healthcare professionals. Hence, we aimed to investigate the impact of customized screening intervals on the daily incidence of DDI alerts. An interrupted time series analysis was performed at the University Hospitals Leuven to evaluate the impact of a pragmatic intervention on the daily incidence of DDI alerts per 100 prescriptions.

Optimization of bacteriophage therapy for difficult-to-treat musculoskeletal infections: a bench-to-bedside perspective.

Given the increasing threat of antimicrobial resistance, scientists are urgently seeking adjunct antimicrobial strategies, such as phage therapy (PT). However, despite promising results for the treatment of musculoskeletal infections in our center, crucial knowledge gaps remain. Therefore, a prospective observational study (PHAGEFORCE) and a multidisciplinary approach was set up to achieve and optimize standardized treatment guidelines.

Willingness-to-use and preferences for model-informed antenatal doses: a cross-sectional study among European healthcare practitioners and pregnant women.

Physiological changes in pregnancy may affect drug safety and efficacy, sometimes requiring dose adjustments. Pregnancy-adjusted doses, however, are missing for most medications. Increasingly, pharmacokinetic models can be used for antenatal dose finding.

Ontogeny of Hepatic Organic Cation Transporter-1 in Rat and Human.

The organic cation transporter (OCT)-1 mediates hepatic uptake of cationic endogenous compounds and xenobiotics. To date, limited information exists on how Oct1/OCT1 functionally develops with age in rat and human livers and how this would affect the pharmacokinetics of OCT substrates in children or juvenile animals. The functional ontogeny of rOct/hOCT was profiled in suspended rat (2-57 days old) and human hepatocytes (pediatric liver tissue donors: age 2-12 months) by determining uptake clearance of 4-[4-(dimethylamino)styryl]-N-methylpyridinium iodide (ASP+) as a known rOct/hOCT probe substrate.

Carfilzomib shows therapeutic potential for reduction of liver fibrosis by targeting hepatic stellate cell activation.

Because hepatic stellate cells (HSCs) play a major role in fibrosis, we focused on HSCs as a potential target for the treatment of liver fibrosis. In this study, we attempted to identify drug candidates to inactivate HSCs and found that several proteasome inhibitors (PIs) reduced HSC viability. Our data showed that a second-generation PI, carfilzomib (CZM), suppressed the expression of fibrotic markers in primary murine HSCs at low concentrations of 5 or 10 nM.

Model-informed precision dosing: State of the art and future perspectives.

Model-informed precision dosing (MIPD) stands as a significant development in personalized medicine to tailor drug dosing to individual patient characteristics. MIPD moves beyond traditional therapeutic drug monitoring (TDM) by integrating mathematical predictions of dosing, and considering patient-specific factors (patient characteristics, drug measurements) as well as different sources of variability. For this purpose, rigorous model qualification is required for the application of MIPD in patients.

Decreased Kidney Function Explains Higher Vancomycin Exposure in Older Adults.

Introduction: Older adults face a higher risk of vancomycin-related toxicity given their (patho)-physiological changes, making early management of supratherapeutic exposure crucial. Yet, data on vancomycin exposure in older adults is scarce. This study aims to compare vancomycin concentrations between older and younger patients, emphasizing supratherapeutic concentrations and the effect of patient characteristics.

EU-US data transfers: an enduring challenge for health research collaborations.

EU-US data transfers for health research remain a particularly thorny issue in view of the stringent rules of the EU General Data Protection Regulation (GDPR) and the challenges related to US mass surveillance programs, particularly the manner in which US law enforcement and national security agencies can access personal data originating from the EU. Since the entry into force of the GDPR, evidence of impeded collaborations is increasing, particularly in the case of sharing data with US public institutions. The adoption of a new EU-US adequacy decision in July 2023 does not hold the promise for a long-lasting solution due to the risks of being challenged and invalidated - yet again - at the Court of Justice of the EU.

Transforming healthcare: A pilot study to improve primary healthcare professionals' self-management support behaviour through blended learning.

Background: Self-management of a chronic condition is a complex but increasingly important issue. However, a supportive attitude and behaviour among healthcare professionals is hampered by a lack of awareness, knowledge and motivation. In addition, the role of professionals in supporting self-management seems unclear.

Dose optimization of β-lactam antibiotics in children: from population pharmacokinetics to individualized therapy.

Introduction: β-Lactams are the most widely used antibiotics in children. Their optimal dosing is essential to maximize their efficacy, while minimizing the risk for toxicity and the further emergence of antimicrobial resistance. However, most β-lactams were developed and licensed long before regulatory changes mandated pharmacokinetic studies in children.

Preconception Physical Exercise Is Associated with Phenotype-Specific Cardiovascular Alterations in Women at Risk for Gestational Hypertensive Disorders.

: Gestational hypertensive disorders (GHD) pose significant maternal and fetal health risks during pregnancy. Preconception physical exercise has been associated with a lower incidence of GHD, but insights into the cardiovascular mechanisms remain limited. This study aimed to evaluate the effect of preconception physical exercise on the complete cardiovascular functions of women at risk for GHD in a subsequent pregnancy.

Very low monomethyl fumarate exposure via human milk: a case report-a contribution from the ConcePTION project.

Introduction: While breastfeeding is recommended, knowledge regarding medicine transfer to human milk and its safety for nursing infants is limited. Only one paper has previously described dimethyl fumarate (DMF) transfer during breastfeeding in two patients at 5 and 6 months postpartum, respectively. The current case report describes maternal pharmacokinetic data of monomethyl fumarate (MMF), the active metabolite of DMF, and infant exposure estimations of MMF at 3 months postpartum.

Bilateral Common Carotid Artery Stenosis in Mice: A Model of Chronic Cerebral Hypoperfusion-Induced Vascular Cognitive Impairment.

Vascular cognitive impairment (VCI) is a syndrome defined as cognitive decline caused by vascular disease and is associated with various types of dementia. Chronic cerebral hypoperfusion (CCH) is one of the major contributors to VCI. Among the various rodent models used to study CCH-induced VCI, we have found the mouse bilateral common carotid artery stenosis (BCAS) model to be highly suitable.

The PPP2R1A cancer hotspot mutant p.R183W increases clofarabine resistance in uterine serous carcinoma cells by a gain-of-function mechanism.

Purpose: Uterine serous carcinoma (USC) is generally associated with poor prognosis due to a high recurrence rate and frequent treatment resistance; hence, there is a need for improved therapeutic strategies. Molecular analysis of USC identified several molecular markers, useful to improve current treatments or identify new druggable targets. PPP2R1A, encoding the Aα subunit of the tumor suppressive Ser/Thr phosphatase PP2A, is mutated in up to 40% of USCs.

The impact of a patient-centred care pathway for patients treated with oral anticancer drugs: A multicentre pre-posttest study in Flanders.

Rationale: In the Collaborative Network To Take Responsibility for Oral Anticancer Therapy (CONTACT) project, an evidence-based and patient-centred care(PCC) pathway was implemented in 12 oncology departments in Flanders. The care pathway was developed in cocreation by an interdisciplinary project team, and tailored to the local hospital context.

Aims And Objectives: In this study, the impact of the care pathways on quality of PCC and other patient outcomes was investigated.

Pharmacists in oncology: Evidence still needed, but teaching comes first.

Introduction: The pharmacy profession faces a lack of evidence pertaining to pharmaceutical care in oncology, both in terms of its effectiveness and its integration into clinical practice. While Europe-based pharmacists are active in many therapeutic areas, their role in cancer care is less defined. Conversely, the complexity of oncology, increasing cancer cases, and evolving therapies highlight the potential for pharmacists in this field.