Understanding the Pharmacokinetics of Antibiotics in Pregnancy:Is There a Role for Therapeutic Drug Monitoring? A Narrative Review

Purpose: Antibiotics are commonly used during pregnancy. However, physiological changes during pregnancy can affect the pharmacokinetics of drugs, including antibiotics, used during this period. Pharmacokinetic evaluations have shed light on how antibiotics are affected during pregnancy and have influenced dosing recommendations in this context. Methods: A narrative review was conducted and included reports providing data reflecting drug distribution and exposure in the context of pregnancy. Results: Pharmacokinetic parameters of antibiotics in pregnancy and transplacental passage of antibiotics are comprehensively presented. Conclusions: Knowledge about the impact on pharmacokinetics and fetal exposure is especially helpful for complicated or severe infections, including intra-amniotic infection and sepsis in pregnancy, where both mother and fetus are at risk. Further studies are warranted to consolidate the role of therapeutic drug monitoring in complicated or severe infections in pregnant patients

Covid-19 research evidence: An international survey exploring views on useful sources, preferred formats, and accessibility

INTRODUCTION: In a pandemic, stakeholders such as policy makers, clinicians, patients, and the public need access to high-quality, timely, relevant research evidence in a format that is understandable and applicable. OBJECTIVES: An online survey was used to determine where a global audience finds research evidence about COVID-19 and how they prefer to keep up to date. METHODS AND MATERIALS: We conducted an online survey of people interested in research in English and Spanish. We used a convenience sample of people visiting websites and social media accounts of Cochrane, an international organisation that collates systematic reviews of research.  RESULTS: 831 people with various roles and locations responded over a short period with little active promotion. Healthcare professionals, members of the public, and policy influencers wanted research evidence to inform decisions about COVID-19. More than half found research evidence from government websites (52%), international organisations (57%), journals (56%), and evidence collation organisations (60%) useful. People wanted research evidence about COVID-19 formats such as lay summaries (60%), online systematic reviews (60%), short summaries with commentaries (51%), and visual summaries (48%). People preferred to be kept up to date about COVID-19 research via email updates and newsletters, tailored to people’s interests (34%), traditional media (13%) and social media (12%). CONCLUSIONS: It was feasible to collect feedback rapidly using a simple online survey. Websites from official organisations were key sources of COVID-19 research evidence. More research is needed on how best to provide evidence that is easy to access and understand

How to design a study to evaluate therapeutic drug monitoring in infectious diseases?

Background: Therapeutic drug monitoring (TDM) is a tool to personalize and optimize dosing by measuring the drug concentration and subsequently adjusting the dose to reach a target concentration or exposure. The evidence to support TDM is however often ranked as expert opinion. Limitations in study design and sample size have hampered definitive conclusions of the potential added value of TDM. Objectives: We aim to give expert opinion and discuss the main points and limitations of available data from antibiotic TDM trials and emphasize key elements for consideration in design of future clinical studies to quantify the benefits of TDM. Sources: The sources were peer-reviewed publications, guidelines and expert opinions from the field of TDM. Content: This review focuses on key aspects of antimicrobial TDM study design: describing the rationale for a TDM study, assessing the exposure of a drug, assessing susceptibility of pathogens and selecting appropriate clinical endpoints. Moreover we provide guidance on appropriate study design. Implications: This is an overview of different aspects relevant for the conduct of a TDM study. We believe that this paper will help researchers and clinicians to design and conduct high-quality TDM studies

Psychotropic drug concentrations and clinical outcomes in children and adolescents: a systematic review

Introduction: The use of psychotropic drugs in children and adolescents is widespread but associated with suboptimal treatment effects. Therapeutic drug monitoring (TDM) can improve safety of psychotropic drugs in children and adolescents but is not routinely performed. A major reason is that the relationship between drug concentrations and effects is not well known. Areas covered: This systematic review evaluated studies assessing the relationship between psychotropic drug concentrations and clinical outcomes in children and adolescents, including antipsychotics, psychostimulants, alpha-agonists, antidepressants, and mood-stabilizers. PRISMA guidelines were used and a quality assessment of the retrieved studies was performed. Sixty-seven eligible studies involving 24 psychotropic drugs were identified from 9,298 records. The findings were generally heterogeneous and the majority of all retrieved studies were not of sufficient quality. For 11 psychotropic drugs, a relationship between drug concentrations and side-effects and/or effectiveness was evidenced in reasonably reported and executed studies, but these findings were barely replicated. Expert opinion: In order to better support routine TDM in child- and adolescent psychiatry, future work must improve in aspects of study design, execution and reporting to demonstrate drug concentration-effect relationships. The quality criteria proposed in this work can guide future TDM research. Systematic review protocol and registration PROSPERO CRD42018084159

Environmental and genetic Risks Factors for Post-Transplant Lymphoproliferative Disease

Thèse soutenue à l'UMR-S850 Directeur de thèse : Pr Pierre Marque