Exploring NICU nurses' views of a novel genetic point-of-care test identifying neonates at risk of antibiotic-induced ototoxicity: A qualitative study.

Aim: To explore the views of neonatal intensive care nursing staff on the deliverability of a novel genetic point-of-care test detecting a genetic variant associated with antibiotic-induced ototoxicity.

Design: An interpretive, descriptive, qualitative interview study.

Methods: Data were collected using semi-structured interviews undertaken between January and November 2020.

Introduction to pharmacogenetics.

There is considerable interindividual variability in the effectiveness and safety of medicines. Although the reasons for this are multifactorial, it is well recognised that genetic changes impacting the absorption or metabolism of these drugs play a significant contributory role. Understanding how these pharmacogenetic variants impact response to medicines, and leveraging this knowledge to guide prescribing, could have significant benefits for patients and health services.

Patient and public involvement in hearing research: opportunities, impact and reflections with case studies from the Manchester Centre for Audiology and Deafness.

Objective: Patient and public involvement (PPI) in research improves relevance to end users and improves processes including recruitment participants. PPI in our research has gone from being non-existent to ubiquitous over a few years. We provide critical reflections on the benefits and challenges of PPI.

Pharmacogenetics to Avoid Loss of Hearing (PALOH) trial: a protocol for a prospective observational implementation trial.

Introduction: In conjunction with a beta-lactam, aminoglycosides are the first-choice antibiotic for empirical treatment of sepsis in the neonatal period. The m.1555A>G variant predisposes to ototoxicity after aminoglycoside administration and has a prevalence of 1 in 500.

Clinical Pharmacogenetics Implementation Consortium Guideline for the Use of Aminoglycosides Based on MT-RNR1 Genotype.

Aminoglycosides are widely used antibiotics with notable side effects, such as nephrotoxicity, vestibulotoxicity, and sensorineural hearing loss (cochleotoxicity). MT-RNR1 is a gene that encodes the 12s rRNA subunit and is the mitochondrial homologue of the prokaryotic 16s rRNA. Some MT-RNR1 variants (i.

Using a biomarker acutely to identify babies at risk of serious adverse effects from antibiotics: where is the 'Terrible Moral and Medical Dilemma'?

We thank Parker and Wright for engaging in this roundtable debate in such a spirited way. The 'Pharmacogenetic [test] to Avoid Loss of Hearing' (PALOH) Trial is the first time a genetic point of care test has been applied in the acute neonatal setting; therefore, it is not surprising that questions have been raised which require debate, discussion and clarification. Parker and Wright misattribute several assumptions to the roundtable authors, which we would like to clarify here.

New insights into the clinical and molecular spectrum of the novel CYFIP2-related neurodevelopmental disorder and impairment of the WRC-mediated actin dynamics.

Purpose: A few de novo missense variants in the cytoplasmic FMRP-interacting protein 2 (CYFIP2) gene have recently been described as a novel cause of severe intellectual disability, seizures, and hypotonia in 18 individuals, with p.Arg87 substitutions in the majority.

Methods: We assembled data from 19 newly identified and all 18 previously published individuals with CYFIP2 variants.

Genetic testing in the acute setting: a round table discussion.

Genetic testing has historically been performed in the context of chronic disease and cancer diagnostics. The timelines for these tests are typically measured in days or weeks, rather than in minutes. As such, the concept that genetic information might be generated and then used to alter management in the acute setting has, thus far, not been feasible.

Spatially clustering de novo variants in CYFIP2, encoding the cytoplasmic FMRP interacting protein 2, cause intellectual disability and seizures.

CYFIP2, encoding the evolutionary highly conserved cytoplasmic FMRP interacting protein 2, has previously been proposed as a candidate gene for intellectual disability and autism because of its important role linking FMRP-dependent transcription regulation and actin polymerization via the WAVE regulatory complex (WRC). Recently, de novo variants affecting the amino acid p.Arg87 of CYFIP2 were reported in four individuals with epileptic encephalopathy.

Acute carbon monoxide toxicity in a paediatric cohort: analysis of 10 boys poisoned during a scuba diving lesson.

Background: Recent public health strategies have contributed towards a significant reduction in the incidence of carbon monoxide (CO) poisonings. When events do occur, symptoms can vary dramatically depending on the carboxyhaemoglobin level and individual factors. Most reports to date focus on individual cases or larger retrospective reviews of diverse cohorts.