Pharmacometric Analysis to Describe Pharmacokinetics and Exposure-Efficacy Response of Ivermectin in Adolescents Infected with Trichuris trichiura.

The efficacy of the combination therapy of albendazole and ivermectin against Trichuris trichiura infection is higher in Tanzania than in Côte d'Ivoire. This study therefore aimed to investigate the difference between the population pharmacokinetics (PK) at these study sites and to determine if an exposure-response analysis could explain the low efficacy of the combination therapy in Côte d'Ivoire. Twenty-four participants (aged 12-19 years) receiving single doses of ivermectin (200 µg/kg) and albendazole (400 mg) were included in the population PK modeling.

Perivascular space enlargement accelerates in ageing and Alzheimer's disease pathology: evidence from a three-year longitudinal multicentre study.

Background: Perivascular space (PVS) enlargement in ageing and Alzheimer's disease (AD) and the drivers of such a structural change in humans require longitudinal investigation. Elucidating the effects of demographic factors, hypertension, cerebrovascular dysfunction, and AD pathology on PVS dynamics could inform the role of PVS in brain health function as well as the complex pathophysiology of AD.

Methods: We studied PVS in centrum semiovale (CSO) and basal ganglia (BG) computationally over three to four annual visits in 503 participants (255 females; mean = 70.

Computing optimal drug dosing regarding efficacy and safety: the enhanced OptiDose method in NONMEM.

Recently, an optimal dosing algorithm (OptiDose) was developed to compute the optimal drug doses for any pharmacometrics model for a given dosing scenario. In the present work, we enhance the OptiDose concept to compute optimal drug dosing with respect to both efficacy and safety targets. Usually, these are not of equal importance, but one is a top priority, that needs to be satisfied, whereas the other is a secondary target and should be achieved as good as possible without failing the top priority target.

Pharmacometrics to Evaluate Dosing of the Patient-Friendly Ivermectin CHILD-IVITAB in Children ≥ 15 kg and <15 kg.

The antiparasitic drug ivermectin is approved for persons > 15 kg in the US and EU. A pharmacometric (PMX) population model with clinical PK data was developed (i) to characterize the effect of the patient-friendly ivermectin formulation CHILD-IVITAB on the absorption process and (ii) to evaluate dosing for studies in children < 15 kg. Simulations were performed to identify dosing with CHILD-IVITAB associated with similar exposure coverage in children ≥ 15 kg and < 15 kg as observed in adults receiving the reference formulation STROMECTOL.

Surgeon-Scientists Going Extinct: Last Call for Action or Too Late?

Objective: To define the concept of surgeon-scientists and identify the root causes of their decline in number and impact. The secondary aim was to provide actionable remedies.

Background: Surgeons who conduct research in addition to patient care are referred to as "surgeon-scientists.

Milestones in Surgical Complication Reporting: Clavien-Dindo Classification 20 Years and Comprehensive Complication Index 10 Years.

Objective: To provide improved guidance for the consistent application of the Clavien-Dindo classification (CDC) and Comprehensive Complication Index (CCI ® ) in challenging clinical scenarios.

Background: Standardized outcome reporting is key for the proper assessment of surgical procedures. A recent consensus conference recommended the CDC and the CCI ® for assessing postoperative morbidity.

Understanding time to peak effect of propofol as sole agent on bispectral index in children aged 2-12 years.

Background: The pharmacodynamics of propofol in children have previously been described with the proprietary bispectral index (BIS) as an effect-site marker, and it has been suggested that the rate of onset of propofol might be age dependent, that is, a shorter time to peak effect in younger children. However, these analyses were potentially confounded by co-administered drugs, in particular opioids and benzodiazepines. Thus, the goal of this prospective study was to characterize the influence of age and weight on the onset of hypnotic effects from propofol, reflected by the time to peak of propofol effect-site concentration in the absence of additional drugs.

Revolutionizing Liver Transplantation: Transitioning to an Elective Procedure Through Ex Situ Normothermic Machine Perfusion - A Benefit Analysis.

Objective: To assess the impact of normothermic machine perfusion (NMP) on patients, medical teams, and costs by gathering global insights and exploring current limitations.

Background: NMP for ex situ liver graft perfusion is gaining increasing attention for its capability to extend graft preservation. It has the potential to transform liver transplantation (LT) from an urgent to a purely elective procedure, which could revolutionize LT logistics, reduce burden on patients and health care providers, and decrease costs.

Understanding Drug Exposure and Trichuris trichiura Cure Rates: A Pharmacometric Approach for Albendazole-Ivermectin Co-medication in Tanzania and Côte d'Ivoire.

Background And Objective: Trichuriasis caused by the human whipworm Trichuris trichiura poses a significant public health concern. Albendazole-ivermectin co-medication is currently the most effective treatment. Studies conducted in Tanzania and Côte d'Ivoire unveiled differences in efficacy for albendazole-ivermectin combination therapy in both countries.

Novel Patient-Friendly Orodispersible Formulation of Ivermectin is Associated With Enhanced Palatability, Controlled Absorption, and Less Variability: High Potential for Pediatric Use.

Ivermectin has been used since the 1980s as an anthelmintic and antiectoparasite agent worldwide. Currently, the only available oral formulation is tablets designed for adult patients. A patient-friendly orodispersible tablet formulation designed for pediatric use (CHILD-IVITAB) has been developed and is entering early phase clinical trials.

Applying Neural ODEs to Derive a Mechanism-Based Model for Characterizing Maturation-Related Serum Creatinine Dynamics in Preterm Newborns.

Serum creatinine in neonates follows complex dynamics due to maturation processes, most pronounced in the first few weeks of life. The development of a mechanism-based model describing complex dynamics requires high expertise in pharmacometric (PMX) modeling and substantial model development time. A recently published machine learning (ML) approach of low-dimensional neural ordinary differential equations (NODEs) is capable of modeling such data from newborns automatically.

Development of an augmented reality guidance system for head and neck cancer resection.

The use of head-mounted augmented reality (AR) for surgeries has grown rapidly in recent years. AR aids in intraoperative surgical navigation through overlaying three-dimensional (3D) holographic reconstructions of medical data. However, performing AR surgeries on complex areas such as the head and neck region poses challenges in terms of accuracy and speed.

Pharmacometric in silico studies used to facilitate a national dose standardisation process in neonatology - application to amikacin.

Background And Aims: Pharmacometric in silico approaches are frequently applied to guide decisions concerning dosage regimes during the development of new medicines. We aimed to demonstrate how such pharmacometric modelling and simulation can provide a scientific rationale for optimising drug doses in the context of the Swiss national dose standardisation project in paediatrics using amikacin as a case study.

Methods: Amikacin neonatal dosage is stratified by post-menstrual age (PMA) and post-natal age (PNA) in Switzerland and many other countries.

National survey in Switzerland calls for improved diagnosis and treatment in children with scabies.

Aim Of The Study: The global prevalence of scabies is estimated to be up to 200 million cases annually, with young children particularly affected. In Europe, most cases are thought to originate in migrant populations. Scabies management is challenging in children.

Glucose controls lipolysis through Golgi PtdIns4P-mediated regulation of ATGL.

Metabolic crosstalk of the major nutrients glucose, amino acids and fatty acids (FAs) ensures systemic metabolic homeostasis. The coordination between the supply of glucose and FAs to meet various physiological demands is especially important as improper nutrient levels lead to metabolic disorders, such as diabetes and metabolic dysfunction-associated steatohepatitis (MASH). In response to the oscillations in blood glucose levels, lipolysis is thought to be mainly regulated hormonally to control FA liberation from lipid droplets by insulin, catecholamine and glucagon.

Curare and GenExVis: a versatile toolkit for analyzing and visualizing RNA-Seq data.

Even though high-throughput transcriptome sequencing is routinely performed in many laboratories, computational analysis of such data remains a cumbersome process often executed manually, hence error-prone and lacking reproducibility. For corresponding data processing, we introduce Curare, an easy-to-use yet versatile workflow builder for analyzing high-throughput RNA-Seq data focusing on differential gene expression experiments. Data analysis with Curare is customizable and subdivided into preprocessing, quality control, mapping, and downstream analysis stages, providing multiple options for each step while ensuring the reproducibility of the workflow.

Risk factors for intracerebral hemorrhage in small-vessel disease and non-small-vessel disease etiologies-an observational proof-of-concept study.

Background: Sporadic cerebral small-vessel disease (CSVD), i.e., hypertensive arteriopathy (HA) and cerebral amyloid angiopathy (CAA), is the main cause of spontaneous intracerebral hemorrhage (ICH).

Pharmacokinetics-Based Pediatric Dose Evaluation and Optimization Using Saliva - A Case Study.

Understanding pharmacokinetics (PK) in children is a prerequisite to determine optimal pediatric dosing. As plasma sampling in children is challenging, alternative PK sampling strategies are needed. In this case study we evaluated the suitability of saliva as alternative PK matrix to simplify studies in infants, investigating metamizole, an analgesic used off-label in infants.

Surgical Outcome Reporting. Moving From a Comic to a Tragic Opera?

Objectives: To assess the current quality of surgical outcome reporting in the medical literature and to provide recommendations for improvement.

Background: In 1996, The Lancet labeled surgery as a "comic opera" mostly referring to the poor quality of outcome reporting in the literature impeding improvement in surgical quality and patient care.

Methods: We screened 3 first-tier and 2 second-tier surgical journals, as well as 3 leading medical journals for original articles reporting on results of surgical procedures published over a recent 18-month period.