Using stated-preferences methods to develop a summary metric to determine successful treatment of children with a surgical condition: a study protocol.

INTRODUCTION: Wide variation in the management of key paediatric surgical conditions in the UK has likely resulted in outcomes for some children being worse than they could be. Consequently, it is important to reduce unwarranted variation. However, major barriers to this are the inability to detect differences between observed and expected hospital outcomes based on the casemix of the children they have treated, and the inability to detect variation in significant outcomes between hospitals. A stated-preference study has been designed to estimate the value key stakeholders place on different elements of the outcomes for a child with a surgical condition. This study proposes to develop a summary metric to determine what represents successful treatment of children with surgical conditions. METHODS AND ANALYSIS: Preferences from parents, individuals treated for surgical conditions as infants/children, healthcare professionals and members of the public will be elicited using paired comparisons and kaizen tasks. A descriptive framework consisting of seven attributes representing types of operations, infections treated in hospital, quality of life and survival was identified. An experimental design has been completed using a D-efficient design with overlap in three attributes and excluding implausible combinations. All participants will be presented with an additional choice task including a palliative scenario that will be used as an anchor. The survey will be administered online. Primary analysis will estimate a mixed multinomial logit model. A traffic light system to determine what combination of attributes and levels represent successful treatment will be created. ETHICS AND DISSEMINATION: Ethics approval to conduct this study has been obtained from the Medical Sciences Inter-Divisional Research Ethics Committee (IDREC) at the University of Oxford (R59631/RE001-05). We will disseminate all of our results in peer-review publications and scientific presentations. Findings will be additionally disseminated through relevant charities and support groups and professional organisations.

A study of diabetic ketoacidosis in the pregnant population in the United Kingdom: Investigating the incidence, aetiology, management and outcomes.

AIM: To estimate the incidence of diabetic ketoacidosis (DKA) among pregnant women, describe its clinical features, management and outcomes and identify the risk factors for the condition. METHODS: A national population-based case-control study was conducted in the UK using the UK Obstetric Surveillance System between April 2019 and September 2020 including all pregnant women with DKA irrespective of the level of blood glucose. The incidence rate of DKA in pregnancy was estimated. A case-control analysis limited to women with type 1 diabetes was performed comparing characteristics of women with DKA (cases) to those of women whose pregnancies were not complicated by DKA (controls). RESULTS: In all, 82 women were identified with DKA in pregnancy; 6.3 per 100,000 maternities (95% CI: 5.0-7.9). No maternal deaths occurred, but perinatal mortality was 12/73 (16%) with 11 stillbirths and one neonatal death. DKA episodes mostly occurred in women with type 1 diabetes (85%) and in the 3rd trimester of pregnancy (71%). Episodes were mainly precipitated by infection (21%), vomiting (21%), steroid therapy (13%) and medication errors (10%). Fifteen percent of women had more than one episode of DKA during their pregnancy. Risk factors associated with DKA among women with type 1 diabetes identified through the case-control analysis were the woman and/or partner not being in a paid employment and having at least one microvascular complication of diabetes before pregnancy. CONCLUSION: DKA in pregnancy was associated with high perinatal mortality and was linked with factors related to socio-economic deprivation, mental health problems and long-term difficulties with glycaemic control.

The top 10 research priorities in diabetes and pregnancy according to women, support networks and healthcare professionals.

AIMS: To undertake a Priority Setting Partnership (PSP) to establish priorities for future research in diabetes and pregnancy, according to women with experience of pregnancy, and planning pregnancy, with any type of diabetes, their support networks and healthcare professionals. METHODS: The PSP used established James Lind Alliance (JLA) methodology working with women and their support networks and healthcare professionals UK-wide. Unanswered questions about the time before, during or after pregnancy with any type of diabetes were identified using an online survey and broad-level literature search. A second survey identified a shortlist of questions for final prioritisation at an online consensus development workshop. RESULTS: There were 466 responses (32% healthcare professionals) to the initial survey, with 1161 questions, which were aggregated into 60 unanswered questions. There were 614 responses (20% healthcare professionals) to the second survey and 18 questions shortlisted for ranking at the workshop. The top 10 questions were: diabetes technology, the best test for diabetes during pregnancy, diet and lifestyle interventions for diabetes management during pregnancy, emotional and well-being needs of women with diabetes pre- to post-pregnancy, safe full-term birth, post-natal care and support needs of women, diagnosis and management late in pregnancy, prevention of other types of diabetes in women with gestational diabetes, women's labour and birth experiences and choices and improving planning pregnancy. CONCLUSIONS: These research priorities provide guidance for research funders and researchers to target research in diabetes and pregnancy that will achieve greatest value and impact.

Depression of glutamate and GABA release by presynaptic GABAB receptors in the entorhinal cortex in normal and chronically epileptic rats.

Presynaptic GABA(B) receptors (GABA(B)R) control glutamate and GABA release at many synapses in the nervous system. In the present study we used whole-cell patch-clamp recordings of spontaneous excitatory and inhibitory synaptic currents in the presence of TTX to monitor glutamate and GABA release from synapses in layer II and V of the rat entorhinal cortex (EC)in vitro. In both layers the release of both transmitters was reduced by application of GABA(B)R agonists. Quantitatively, the depression of GABA release in layer II and layer V, and of glutamate release in layer V was similar, but glutamate release in layer II was depressed to a greater extent. The data suggest that the same GABA(B)R may be present on both GABA and glutamate terminals in the EC, but that the heteroreceptor may show a greater level of expression in layer II. Studies with GABA(B)R antagonists suggested that neither the auto- nor the heteroreceptor was consistently tonically activated by ambient GABA in the presence of TTX. Studies in EC slices from rats made chronically epileptic using a pilocarpine model of temporal lobe epilepsy revealed a reduced effectiveness of both auto- and heteroreceptor function in both layers. This could suggest that enhanced glutamate and GABA release in the EC may be associated with the development of the epileptic condition.