Differences in access to Emergency Paediatric Intensive Care and care during Transport (DEPICT): study protocol for a mixed methods study

Introduction Following centralisation of UK paediatric intensive care, specialist retrieval teams were established who travel to general hospitals to stabilise and transport sick children to regional paediatric intensive care units (PICUs). There is national variation among these PICU retrieval teams (PICRTs) in terms of how quickly they reach the patient’s bedside and in the care provided during transport. The impact of these variations on clinical outcomes and the experience of stakeholders (patients, families and healthcare staff) is however unknown. The primary objective of this study is to address this evidence gap. Methods and analysis This mixed-methods project involves the following: (1) retrospective analysis of linked data from routine clinical audits (2014–2016) to assess the impact of service variations on 30-day mortality and other secondary clinical outcomes; (2) a prospective questionnaire study conducted at 24 PICUs and 9 associated PICRTs in England and Wales over a 12-month period in 2018 to collect experience data from parents of transported children as well as qualitative analysis of in-depth interviews with a purposive sample of patients, parents and staff to assess the impact of service variations on patient/family experience; (3) health economic evaluation analysing transport service costs (and other associated costs) against lives saved and longer term measurements of quality of life at 12 months in transported children and (4) mathematical modelling evaluating the costs and potential impact of different service configurations. A final work stream involves a series of stakeholder workshops to synthesise study findings and generate recommendations. Ethics and dissemination The study has been reviewed and approved by the Health Research Authority, ref: 2 18 569. Study results will be actively disseminated through peer-reviewed journals, conference presentations, social media, print and broadcast media, the internet and stakeholder workshops

Proteolytic Regulation of the Mitochondrial cAMP-Dependent Protein Kinase

The mitochondrial cAMP-dependent protein kinase (PKA) is activatable in a cAMP-independent fashion. The regulatory (R) subunits of the PKA holoenzyme (R(2)C(2)), but not the catalytic (C) subunits, suffer proteolysis upon exposure of bovine heart mitochondria to digitonin, Ca(2+), and a myriad of electron transport inhibitors. Selective loss of both the RI- and RII-type subunits was demonstrated via western blot analysis and activation of the C subunit was revealed by phosphorylation of a validated PKA peptide substrate. Selective proteolysis transpires in a calpain-dependent fashion as demonstrated by exposure of the R and C subunits of PKA to calpain and by attenuation of R and C subunit proteolysis in the presence of calpain inhibitor I. By contrast, exposure of mitochondria to cAMP fails to promote R subunit degradation, although it does result in enhanced C subunit catalytic activity. Treatment of mitochondria with electron transport chain inhibitors rotenone, antimycin A, sodium azide, and oligomycin, as well as an uncoupler of oxidative phosphorylation, also elicits enhanced C subunit activity. These results are consistent with the notion that signals, originating from cAMP-independent sources, elicit enhanced mitochondrial PKA activity

James Franklin Collins correspondence.

Senders Pe-Sa (1887-1919