Feasibility of developing children's Pill School within a UK hospital

OBJECTIVE: We assessed the feasibility of introducing an intervention (children's Pill School-PS) within a UK hospital to provide swallowing training for children, identified the proportion of children who can be switched from oral liquid medicines to pills and assessed children/parents' opinions about the PS training. METHODS: 30 inpatient children (aged 3-18 years; taking oral liquid medicines; their liquid medications assessed suitable for switching to pills; can (and their parents) speak/understand English were included. Training sessions were delivered using hard sweets of different sizes. RESULTS: 87% (26) of children successfully learnt how to swallow pills after one training session (mean duration 14.5 min), and 92% (24) were discharged on pills. 75 prescribed oral liquid medications were deemed suitable for switching to pills. Of these, 89% (67) were switched successfully. CONCLUSION: Children as young as 3 years were successful in swallowing pills after training. Providing children PS training session within hospital is feasible and acceptable to children and their parents

Genomic–transcriptomic evolution in lung cancer and metastasis

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis

Pharmacokinetic and pharmacodynamic evidence of adrenaline administered via auto-injector for anaphylactic reactions: A review of literature

Anaphylaxis is a severe allergic reaction that can lead to death if not treated quickly. Adrenaline (epinephrine) is the first‐line treatment for anaphylaxis and its prompt administration is vital to reduce mortality. Following a number of high‐profile cases, serious concerns have been raised, both about the optimal dose of intramuscular adrenaline via an auto‐injector and the correct needle length to ensure maximal penetration every time. To date, the public data are sparse on the pharmacokinetics–pharmacodynamics of adrenaline administered via an auto‐injector. The limited available literature showed a huge variation in the plasma concentrations of adrenaline administered through an auto‐injector, as well as variations in the auto‐injector needle length. Hence, delivering an effective dose during an anaphylaxis remains a challenge for both patients and healthcare professionals. Collaborative work between pharmacokinetics–pharmacodynamics experts, clinical triallists and licence holders is imperative to address this gap in evidence so that we can improve outcomes of anaphylaxis. In addition, we advise inclusion of expertise of human factors in usability studies given the necessity of carer or self‐administration in the uniquely stressful nature of anaphylaxis