Genotype-Guided Asthma Treatment Reduces Exacerbations in Children: Meta-Analysis of Two RCTs.

Background: Long-acting beta2-agonists (LABA) in combination with inhaled corticosteroids (ICS) are commonly used to treat asthma, however, some children lack response to the addition of LABA. This might be partially due to the presence of the Arg16Gly polymorphism, encoded by rs1042713 G>A in the ADRB2 gene. Carrying the A allele (Arg16) at this variant has been associated with an increased risk of exacerbations despite LABA treatment.

Defining the pharmacokinetic/pharmacodynamic index of piperacillin/tazobactam within a hollow-fibre infection model to determine target attainment in intensive care patients.

Background: It is important to optimize dosing schemes of antibiotics to maximize the probability of therapeutic success. The recommended pharmacokinetic/pharmacodynamic (PK/PD) index for piperacillin/tazobactam therapy in clinical studies ranges widely (50%-100% ). Dosing schemes failing to achieve PK/PD targets may lead to negative treatment outcomes.

Safety of Antenatal Predniso(lo)ne and Dexamethasone on Fetal, Neonatal and Childhood Outcomes: A Systematic Review.

Context: Due to ethical considerations, antenatal dose finding for prednisolone and dexamethasone in pregnant women is limited, leading to a knowledge gap.

Objective: In order to guide the clinician in weighing benefits vs risks, the aim is to systematically review the current literature on the side effects of antenatal predniso(lo)ne and dexamethasone use on the fetus, newborn, and (pre)pubertal child.

Evidence Acquisition: The search was performed in PubMed/MEDLINE and Embase using prespecified keywords and Medical Subject Headings.

Persistence of parental-reported asthma at early ages: A longitudinal twin study.

Background: Currently, we cannot predict whether a pre-school child with asthma-like symptoms will have asthma at school age. Whether genetic information can help in this prediction depends on the role of genetic factors in persistence of pre-school to school-age asthma. We examined to what extent genetic and environmental factors contribute to persistence of asthma-like symptoms at ages 3 to asthma at age 7 using a bivariate genetic model for longitudinal twin data.

Imatinib in patients with severe COVID-19: a randomised, double-blind, placebo-controlled, clinical trial.

Background: The major complication of COVID-19 is hypoxaemic respiratory failure from capillary leak and alveolar oedema. Experimental and early clinical data suggest that the tyrosine-kinase inhibitor imatinib reverses pulmonary capillary leak.

Methods: This randomised, double-blind, placebo-controlled, clinical trial was done at 13 academic and non-academic teaching hospitals in the Netherlands.

Early-life antibiotic use and risk of attention-deficit hyperactivity disorder and autism spectrum disorder: results of a discordant twin study.

Background: Development of the gut-brain axis in early life may be disturbed by antibiotic use. It has been hypothesized that this disturbance may contribute to development of neurodevelopmental disorders, including autism spectrum disorder and attention-deficit hyperactivity disorder. We aimed to assess the association between antibiotic use in early life and the risk of developing attention-deficit hyperactivity disorder or autism spectrum disorder, while controlling for shared genetic and environmental factors in a discordant twin design.

Adolescents' experiences with patient engagement in respiratory medicine.

Objective: Adolescent engagement in decision-making processes in health care and research in the field of chronic respiratory diseases is rare but increasingly recognized as important. The aim of this study was to reflect on adolescents' motives and experiences in the process of establishing an advisory council for adolescents with a chronic respiratory disease.

Methods: A qualitative evaluation study was undertaken to assess the process of starting an advisory youth council in a tertiary hospital in the Netherlands.

Early-life antibiotic use and risk of asthma and eczema: results of a discordant twin study.

Rationale: Early-life antibiotic use has been associated with the development of atopic diseases, but the aetiology remains unclear. To elucidate the aetiology, we used a discordant twin design to control for genetic and environmental confounding.

Methods: We conducted a retrospective cohort study in twins aged 3-10 years from the Netherlands Twin Register (NTR, n=35 365) and a replication study in twins aged 9 years from the Childhood and Adolescent Twin Study in Sweden (CATSS, n=7916).

Precision medicine in childhood asthma.

Purpose Of Review: Childhood asthma is a heterogeneous disease and many children have uncontrolled disease. Therefore an individualized approach is needed to improve asthma outcomes in children. Precision medicine using clinical characteristics, biomarkers, and the rapidly involving field of genomics and pharmacogenomics aims to achieve asthma control and reduce future risks with less side-effects in individual children with asthma.

Genetic Variations and Cisplatin Nephrotoxicity: A Systematic Review.

Nephrotoxicity is a notable adverse effect in cisplatin treated patients characterized by tubular injury and/or increased serum creatinine (SCr) with incidence varying from 20 to 70%. Pharmacogenomics has been shown to identify strongly predictive genetic markers to help determine which patients are more likely to experience, for example, a serious adverse drug reaction or receive optimal benefit through enhanced efficacy. Genetic variations have been reported to influence the risk of cisplatin nephrotoxicity; however, a comprehensive overview is lacking.

Pharmacogenetics of inhaled long-acting beta2-agonists in asthma: A systematic review.

Background: Long-acting beta2-agonists (LABA) are recommended in asthma therapy; however, not all asthma patients respond well to LABA. We performed a systematic review on genetic variants associated with LABA response in patients with asthma.

Methods: Articles published until April 2017 were searched by two authors using PubMed and EMBASE.

Treatment response heterogeneity in asthma: the role of genetic variation.

Asthmatic patients show a large heterogeneity in response to asthma medication. Rapidly evolving genotyping technologies have led to the identification of various genetic variants associated with treatment outcomes. Areas covered: This review focuses on the current knowledge of genetic variants influencing treatment response to the most commonly used asthma medicines: short- and long-acting beta-2 agonists (SABA/LABA), inhaled corticosteroids (ICS) and leukotriene modifiers.

Experience using high-dose glucose-insulin-potassium (GIK) in critically ill patients.

Purpose: To audit the use of GIK in terms of safety, haemodynamic effects, and impact on catecholamine dosage.

Materials And Methods: A retrospective, descriptive, evaluative audit of GIK use within the adult ICU of a London teaching hospital was conducted. Rescue therapy of GIK (up to 1.