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There is currently no FDA-approved disease-modifying therapy for diabetic peripheral neuropathy (DPN). Nerve conduction velocity (NCV) is an established primary endpoint of disease-modifying therapies in DPN and clinical trials have been powered with an assumed decline of 0.5 m/s/year. This paper sought to establish the time-dependent change in NCV associated with a placebo, compared to that observed in the active intervention group. A literature search identified twenty-one double-blind, randomised controlled trials in DPN of ≥1 year duration conducted between 1971 and 2021. We evaluated changes in neurophysiology, with a focus on peroneal motor and sural sensory NCV and amplitude in the placebo and treatment groups. There was significant variability in the change and direction of change (reduction/increase) in NCV in the placebo arm, as well as variability influenced by the anatomical site of neurophysiological measurement within a given clinical trial. A critical re-evaluation of efficacy trials should consider placebo-adjusted effects and present the placebo-subtracted change in NCV rather than assume a universal annual decline of 0.5 m/s/year. Importantly, endpoints such as corneal confocal microscopy (CCM) have demonstrated early nerve repair, whilst symptoms and NCV have not changed, and should thus be considered as a viable alternative. [ABSTRACT FROM AUTHOR]

Introduction Differences in the management of diabetic ketoacidosis (DKA), despite established national guidance, contribute to varied patient outcomes.1 Although single centre audits looking at DKA management exist, it is not currently well recognised if there are measurable differences in outcomes across multiple centres. The aim of this study was to assess differences in the rates of complications and outcomes of people admitted with DKA across UK hospitals. Materials and methods DKA admissions across six hospitals in the UK between October 2021 and September 2022 were included. DKA was defined as glucose >11 mmol/L or known diabetes, serum ketones >3 mmol/L or urinary ketones ++ or more and serum pH<7.3 or bicarbonate <15 mmol/L. People <16 years of age or who selfdischarged before treatment were excluded. Pseudonymised data on complications that comprised hypoglycaemia, hypokalaemia and hyperkalaemia, and outcomes that comprised DKA duration and length of stay were collected. Complications were expressed in median number of episodes, DKA duration in hours, and length of stay in days. The 5th to 95th percentile ranges of collected data were included for all parameters. The Independent-Samples Kruskal-Wallis test was used to compare outcomes across hospitals. Significance was accepted at p<0.05. Results and discussion Since the intention was not to compare but to identify best practices, hospitals were anonymised and coded as A-F. In total, 443 DKA episodes were identified. Between the six hospitals, there were statistically significant differences in the patient length of stay (median in days (5th-95th percentiles), A - 3.6 (1.3-18.5), B - 2.1 (1.0-31.1), C - 2.5 (0.8-29.3), D - 3.5 (1.2-20.8), E - 2.5 (0.7-14.6), F - 3.0 (1.0-13.9); p<0.001), duration of DKA (median in hours (5th-95th percentiles), A - 15.1 (5.8-41.7), B - 13.3 (5.9-49.3), C - 13.4 (4.1-21.2), D -18.5 (4.7-69.0), E -17.1 (7.3-47.9), F -16.3 (4.7-39.4); p = 0.003) and incidence of episodes of hypokalaemia (median (5th-95th percentiles), A - 0 (0-3), B - 0 (0-3), C - 0 (0-1), D - 0 (0-4), E - 0 (0-5), F -0 (0-5); p = 0.003). No statistically significant differences were found in episodes of hyperkalaemia (median (5th-95th percentiles), A - 0 (0-2), B - 0 (0-2), C - 0 (0-3), D - 0 (0-3), E - 0 (0-1), F - 0 (0-2); p = 0.536) and episodes of hypoglycaemia (median (5th-95th percentiles) A - 0 (0-1), B - 0 (0-4), C - 0 (0-1), D - 0 (0-3), E - 0 (0-3), F -0 (0-2); p = 0.198). Conclusion With exceptions of hypoglycaemia and hyperkalaemia, significant interhospital variation in the rates of hypokalaemia, DKA duration and length of stay were observed despite similar guidelines. A centralised DKA database system can aid in identification of best practices and sharing of knowledge with the intention of improving patient outcomes. [ABSTRACT FROM AUTHOR]