ChatGPT in pharmacometrics? Potential opportunities and limitations.

The potential of using ChatGPT in pharmacometrics was explored in this study, with a focus on developing a population pharmacokinetic (PK) model for standard half-life factor VIII. Our results demonstrated that ChatGPT can be utilized to accurately obtain typical PK parameters from literature, generate a population PK model in R and develop an interactive Shiny application to visualize the results. ChatGPT's language generation capabilities enabled the development of R codes with minimal programming knowledge and helped to identify as well fix errors in the code.

Relationship between factor VIII levels and bleeding for rFVIII-SingleChain in severe hemophilia A: A repeated time-to-event analysis.

Publications on the exposure-effect relationships of factor concentrates for hemophilia treatment are limited, whereas such analyses give insight on treatment efficacy. Our objective was to examine the relationship between the dose, factor VIII (FVIII) levels and bleeding for rFVIII-SingleChain (lonoctocog alfa, Afstyla). Data from persons with severe hemophilia A on rFVIII-SingleChain prophylaxis from three clinical trials were combined.

Association between Sports Participation, Factor VIII Levels and Bleeding in Hemophilia A.

Background:  Little is known on how sports participation affects bleeding risk in hemophilia. This study aimed to examine associations between sports participation, factor VIII (FVIII) levels and bleeding in persons with hemophilia A.

Methods:  In this observational, prospective, single-center study, persons with hemophilia A who regularly participated in sports were followed for 12 months.

Coagulation in pediatric extracorporeal membrane oxygenation: A systematic review of studies shows lack of standardized reporting.

Objectives: Extracorporeal membrane oxygenation (ECMO) involves complex coagulation management and frequent hemostatic complications. ECMO practice between centers is variable. To compare results between coagulation studies, standardized definitions and clear documentation of ECMO practice is essential.

Use of rotational thromboelastometry to predict hemostatic complications in pediatric patients undergoing extracorporeal membrane oxygenation: A retrospective cohort study.

Background: The incidence of hemostatic complications in pediatric patients undergoing extracorporeal membrane oxygenation (ECMO) is high. The optimal anticoagulation strategy in children undergoing ECMO is unknown.

Objectives: To study the association between hemostatic complications, coagulation tests, and clinical parameters in pediatric patients undergoing ECMO and their effect on survival.

Patient-relevant health outcomes for hemophilia care: Development of an international standard outcomes set.

Background: Patient-relevant health outcomes for persons with hemophilia should be identified and prioritized to optimize and individualize care for persons with hemophilia. Therefore, an international group of persons with hemophilia and multidisciplinary health care providers set out to identify a globally applicable standard set of health outcomes relevant to all individuals with hemophilia.

Methods: A systematic literature search was performed to identify possible health outcomes and risk adjustment variables.

Emicizumab Dosing in Children and Adults with Hemophilia A: Simulating a User-Friendly and Cost-Efficient Regimen.

Background: When emicizumab is dosed according to label, clinicians are obligated to discard or overdose medication due to discrepancies between calculated dose and vial content. The aim of this study was to compose a cost-efficient emicizumab maintenance dosing regimen using Monte Carlo simulation based on vial size, patient-friendly intervals, and patient characteristics, while striving for similar plasma concentrations as observed in clinical trials.

Methods: Monte Carlo simulations were used to investigate alternative dosing regimens in patients weighing 3 to 150 kg.

Characteristics, management and outcome of prehospital pediatric emergencies by a Dutch HEMS.

Background: In prehospital care, the Helicopter Emergency Medical Service (HEMS) can be dispatched for critically injured or ill children. However, little detail is known about dispatches for children, in terms of the incidence of prehospital interventions and overall mortality. The primary objective of this study is to provide an overview of pediatric patient characteristics and incidence of interventions.

Comparison of the Pharmacokinetic Properties of Extended Half-Life and Recombinant Factor VIII Concentrates by In Silico Simulations.

Background:  The pharmacokinetic (PK) properties of extended half-life (EHL) factor VIII (FVIII) concentrates differ, leading to variation in the optimal dosing regimen for the individual patient. The aim of this study was to establish these PK differences for various EHL FVIII concentrates by in silico simulations.

Methods:  FVIII level over time profiles of rFVIII-SC, BAY 81-8973, rFVIII-Fc, BAX 855, BAY 94-9027, and standard half-life (SHL) rFVIII concentrates were simulated for 1,000 severe hemophilia A patients during steady-state dosing of 40 IU/kg every 72 hours or dosing as advised in the summary of product characteristics (SmPC).

Dosing of factor VIII concentrate by ideal body weight is more accurate in overweight and obese haemophilia A patients.

Aims: Under- and, especially, overdosing of replacement therapy in haemophilia A patients may be prevented by application of other morphometric variables than body weight (BW) to dose factor VIII (FVIII) concentrates. Therefore, we aimed to investigate which morphometric variables best describe interindividual variability (IIV) of FVIII concentrate pharmacokinetic (PK) parameters.

Methods: PK profiling was performed by measuring 3 FVIII levels after a standardized dose of 50 IU kg FVIII concentrate.

A Novel, Enriched Population Pharmacokinetic Model for Recombinant Factor VIII-Fc Fusion Protein Concentrate in Hemophilia A Patients.

Background:  The currently published population pharmacokinetic (PK) models used for PK-guided dosing in hemophilia patients are based on clinical trial data and usually not externally validated in clinical practice. The aim of this study was to validate a published model for recombinant factor VIII-Fc fusion protein (rFVIII-Fc) concentrate and to develop an enriched model using independently collected clinical data if required.

Methods:  Clinical data from hemophilia A patients treated with rFVIII-Fc concentrate (Elocta) participating in the United Kingdom Extended Half-Life Outcomes Registry were collected.

Population pharmacokinetics of factor IX in hemophilia B patients undergoing surgery.

Essentials Factor IX (FIX) dosing using body weight frequently results in under and overdosing during surgery. We aimed to establish a population pharmacokinetic (PK) model describing the perioperative FIX levels. Population PK parameter values for clearance and V1 were 284 mL h70 kg and 5450 mL70 kg.

Performing and interpreting individual pharmacokinetic profiles in patients with Hemophilia A or B: Rationale and general considerations.

Objectives: In a separate document, we have provided specific guidance on performing individual pharmacokinetic (PK) studies using limited samples in persons with hemophilia with the goal to optimize prophylaxis with clotting factor concentrates. This paper, intended for clinicians, aims to describe how to interpret and apply PK properties obtained in persons with hemophilia.

Methods: The members of the Working Party on population PK (PopPK) of the ISTH SSC Subcommittee on Factor VIII and IX and rare bleeding disorders, together with additional hemophilia and PK experts, completed a survey and ranking exercise whereby key areas of interest in the field were identified.

Fifth Åland Island conference on von Willebrand disease.

The fifth Åland Island meeting on von Willebrand disease (VWD) was held on the Åland Islands, Finland, from 22 to 24 September 2016-90 years after the first case of VWD was diagnosed in a patient from the Åland Islands in 1926. This meeting brought together experts in the field of VWD to share knowledge and expertise on current trends and challenges in VWD. Topics included the storage and release of von Willebrand factor (VWF), epidemiology and diagnostics in VWD, treatment of VWD, angiogenesis and VWF inhibitors.

In silico evaluation of limited blood sampling strategies for individualized recombinant factor IX prophylaxis in hemophilia B patients.

Unlabelled: Essentials Individual pharmacokinetic (PK) parameters can be obtained by limited sampling strategies (LSSs). Following 100 IU kg rFIX, LSSs with 1 to 3 samples were evaluated in 5000 simulated subjects. For all LSSs, estimated individual PK parameters showed acceptable bias and precision.

Beyond main effects of gene-sets: harsh parenting moderates the association between a dopamine gene-set and child externalizing behavior.

Background: In a longitudinal cohort study, we investigated the interplay of harsh parenting and genetic variation across a set of functionally related dopamine genes, in association with children's externalizing behavior. This is one of the first studies to employ gene-based and gene-set approaches in tests of Gene by Environment (G × E) effects on complex behavior. This approach can offer an important alternative or complement to candidate gene and genome-wide environmental interaction (GWEI) studies in the search for genetic variation underlying individual differences in behavior.

A population pharmacokinetic model for perioperative dosing of factor VIII in hemophilia A patients.

The role of pharmacokinetic-guided dosing of factor concentrates in hemophilia is currently a subject of debate and focuses on long-term prophylactic treatment. Few data are available on its impact in the perioperative period. In this study, a population pharmacokinetic model for currently registered factor VIII concentrates was developed for severe and moderate adult and pediatric hemophilia A patients (FVIII levels <0.

Perioperative treatment of hemophilia A patients: blood group O patients are at risk of bleeding complications.

Unlabelled: ESSENTIALS: Targeting of factor VIII values is a challenge during perioperative replacement therapy in hemophilia. This study aims to identify the extent and predictors of factor VIII underdosing and overdosing. Blood group O predicts underdosing and is associated with perioperative bleeding.

von Willebrand factor propeptide and the phenotypic classification of von Willebrand disease.

Unlabelled: The ratios between von Willebrand factor propeptide (VWFpp) or factor VIII activity (

Fviii: C) and VWF antigen (VWF:Ag) reflect synthesis, secretion, and clearance of VWF. We aimed to define the pathophysiology of 658 patients with type 1, 2, or 3 von Willebrand disease (VWD) with VWF levels ≤30 U/dL from the Willebrand in The Netherlands (WiN) study using the VWFpp/VWF:Ag and

Fviii: C/VWF:Ag ratios. We evaluated the use of VWFpp in the classification and diagnosis of VWD.

Early respiratory and skin symptoms in relation to ethnic background: the importance of socioeconomic status; the PIAMA study.

Aims: To evaluate ethnic differences in the prevalence of respiratory and skin symptoms in the first two years of life.

Methods: A total of 4146 children participated in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) study. Parents completed questionnaires on respiratory and skin symptoms, ethnic background, and other potential confounders during pregnancy, and at 3 months, 1 year, and 2 years of age.