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.

Vaccine value profile for Klebsiella pneumoniae.

Klebsiella pneumoniae causes community- and healthcare-associated infections in children and adults. Globally in 2019, an estimated 1.27 million (95% Uncertainty Interval [UI]: 0.

Efficacy, Safety, and Population Pharmacokinetics of Eltrombopag in Children with Different Severities of Aplastic Anemia.

Eltrombopag was approved as a first-line treatment for patients older than 2 years old with severe aplastic anemia (SAA). However, data on eltrombopag in children with different types of aplastic anemia (AA), especially non-severe AA (NSAA), are limited. We performed a prospective, single-arm, and observational study to investigate eltrombopag's efficacy, safety, and pharmacokinetics in children with NSAA, SAA, and very severe AA (VSAA).

Inflammatory Type Focal Cerebral Arteriopathy of the Posterior Circulation in Children: A Comparative Cohort Study.

Background: Inflammatory type focal cerebral arteriopathy (FCA-i) in the anterior circulation (AC) is well characterized, and the focal cerebral arteriopathy severity score (FCASS) reflects the severity of the disease. We identified cases of FCA-i in the posterior circulation (PC) and adapted the FCASS to describe these cases.

Methods: In this comparative cohort study, patients from the Swiss NeuroPaediatric Stroke Registry with ischemic stroke due to FCA-i between January 2000 and December 2018 were analyzed.

Novel Modular Walking Orthosis (MOWA) for Powerful Correction of Gait Deviations in Subjects with a Neurological Disease.

This article introduces a novel concept where advanced technologies have been leveraged to produce a modular walking orthosis (MOWA) within a completely digital process chain. All processes of this new supply chain are described step-by-step. The prescription and treatment of lower leg orthoses for individuals with paralysis or muscle weakness, particularly cerebral palsy (CP), are complex.

The current state of pertussis vaccination in pregnancy around the world, with recommendations for improved care: Consensus statements from the Global Pertussis Initiative.

Bordetella pertussis, which causes a respiratory disease known as pertussis ("whooping cough") remains an important global challenge, with the incidence in pertussis cases increasing in recent years. Newborns and infants are at increased risk for severe morbidity and mortality from this bacterium. Vaccination in pregnancy has become an important strategy to both passively transfer immunity as well as prevent infection in pregnant persons, who are a major source of newborn infection, thus attempting to decrease the impact of this serious disease.

Novel Organism Verification and Analysis (NOVA) study: identification of 35 clinical isolates representing potentially novel bacterial taxa using a pipeline based on whole genome sequencing.

Background: Reliable species identification of cultured isolates is essential in clinical bacteriology. We established a new study algorithm named NOVA - Novel Organism Verification and Analysis to systematically analyze bacterial isolates that cannot be characterized by conventional identification procedures MALDI-TOF MS and partial 16 S rRNA gene sequencing using Whole Genome Sequencing (WGS).

Results: We identified a total of 35 bacterial strains that represent potentially novel species.

Preservation of exhaled breath samples for analysis by off-line SESI-HRMS: proof-of-concept study.

Secondary electrospray ionization-high resolution mass spectrometry (SESI-HRMS) is an established technique in the field of breath analysis characterized by its short analysis time, as well as high levels of sensitivity and selectivity. Traditionally, SESI-HRMS has been used for real-time breath analysis, which requires subjects to be at the location of the analytical platform. Therefore, it limits the possibilities for an introduction of this methodology in day-to-day clinical practice.

Impact of the COVID-19 pandemic on antibiotic prescribing in high-prescribing primary care physicians in Switzerland.

Objectives: The aim of this study was to evaluate antibiotic prescribing of medium-to-high prescribing primary care physicians being followed up after the completion of a Swiss national intervention trial of antibiotic prescription audit and feedback in the first SARS-CoV-2 pandemic year.

Methods: We used health insurer based claims data to calculate monthly antibiotic prescription rates per 100 consultations (primary endpoint) and applying interrupted time series (ITS) analysis methods, we estimated the immediate (step change) and sustained effects (slope) of the SARS-CoV-2 epidemic in 2020 on antibiotic prescribing compared to the pre-pandemic trial period from 2017-2019.

Results: We analysed data of 2945 of 3426 physicians (86.

Von Willebrand factor antigen as a marker of disease activity in childhood-onset antineutrophil cytoplasmic antibody-associated vasculitis.

Objective: Von Willebrand factor (VWF) antigen plays a role in vascular inflammation and thrombosis, both of which are important in the pathogenesis of ANCA-associated vasculitis (AAV). Previous work found that VWF correlates with disease activity in childhood-onset primary CNS vasculitis. We sought to determine the relationship between VWF and disease activity over time in children with AAV.

Tuberculosis Case Detection and Guideline Adherence among Child Contacts in Switzerland: A Retrospective Observational Study.

Background: Children exposed to a tuberculosis (TB) index case are at risk of TB infection and disease.

Objectives: The aim of this study was to describe the proportion of child contacts who developed TB infection or disease after exposure and to assess the diagnostic pathways and adherence to current guidelines.

Methods: Retrospective observational study including children ≤16 years of age who had contact to a TB index case between January 2019 and July 2021.

Ratios from full blood count as markers for TB diagnosis, treatment, prognosis: a systematic review.

The monocyte-to-lymphocyte (MLR) and neutrophil-to-lymphocyte (NLR) ratio are calculated from routine full blood counts. The aim of this study was to systematically review MLR and NLR as biomarkers for diagnosis, treatment response monitoring and prognostic biomarker for TB infection or disease. A systematic literature search was conducted in Medline, Embase and the Cochrane Library on 12 January 2022.

Treatment effect of remdesivir on the mortality of hospitalised COVID-19 patients in Switzerland across different patient groups: a tree-based model analysis.

Aims Of The Study: Remdesivir has shown benefits against COVID-19. However, it remains unclear whether, to what extent, and among whom remdesivir can reduce COVID-19-related mortality. We explored whether the treatment response to remdesivir differed by patient characteristics.

Association between perioperative prophylaxis with cefuroxime plus metronidazole or amoxicillin/clavulanic acid and surgical site infections in paediatric uncomplicated appendectomy: a Swiss retrospective cohort study.

Objective: We aimed to evaluate the association between post-appendectomy SSI rates and the two most commonly used regimens for perioperative antimicrobial prophylaxis in Swiss children.

Methods: We conducted a retrospective cohort study, analysing data from the Swiss national SSI surveillance database with a study period from 2014 to 2018. All hospitals undertaking paediatric appendectomies in Switzerland participate in the surveillance.

Meropenem Clearance in a Child With End-stage Renal Disease Undergoing Prolonged Intermittent Renal Replacement Therapy: A Case Report and Literature Review.

Background: Meropenem is frequently used to treat severe infections in critically ill children. However, pharmacokinetic data on meropenem in children with end-stage renal disease (ESRD) undergoing prolonged intermittent renal replacement therapy (PIRRT) is limited. Our objectives were to evaluate meropenem clearance in a child with ESRD with and without PIRRT, compare the results to previous continuous renal replacement therapy studies in children, toddlers and neonates, and assess whether the currently used dose of meropenem is sufficient.

Machine Learning: A New Approach for Dose Individualization.

The application of machine learning (ML) has shown promising results in precision medicine due to its exceptional performance in dealing with complex multidimensional data. However, using ML for individualized dosing of medicines is still in its early stage, meriting further exploration. A systematic review of study designs and modeling details of using ML for individualized dosing of different drugs was performed.

Glutaryl-CoA Dehydrogenase Misfolding in Glutaric Acidemia Type 1.

Glutaric acidemia type 1 (GA1) is a neurotoxic metabolic disorder due to glutaryl-CoA dehydrogenase (GCDH) deficiency. The high number of missense variants associated with the disease and their impact on GCDH activity suggest that disturbed protein conformation can affect the biochemical phenotype. We aimed to elucidate the molecular basis of protein loss of function in GA1 by performing a parallel analysis in a large panel of missense variants using different biochemical and biophysical methodologies.