Reducing the MRI outpatient waiting list through a capacity and demand time series improvement programme.

INTRODUCTION: A capacity and demand improvement initiative commenced in January 2019 with the goal of reducing the growing outpatient waiting list for magnetic resonance imaging (MRI) at Counties Manukau District Health Board (CMDHB). Initial work showed that the capacity (MRI machines and staff) actually outstripped demand, which challenged pre-existing assumptions. This became the basis for interventions to improve efficiency in the department. Interventions undertaken can be split into three distinct categories: (1) matching capacity to demand, (2) waiting list segmentation and (3) redesigning operational systems. METHODS: A capacity and demand time series during 2019 and 2020 was used as the basis for improving waiting list and operational systems. A combination of the Model for Improvement and Lean principles were used to embed operational improvements. Multiple small tests of change were implemented to various aspects of the MRI waiting list process. Staff engagement was central to the success of the quality improvement (QI) initiatives. The radiological information system (RIS) provided the bulk of the data, and this was supplemented with manual data collection. RESULTS: The number of people waiting for an MRI scan decreased from 1,954 at the start of the project to 413 at its conclusion-an overall reduction of 75%. Moreover, the average waiting time reduced from 96.4 days to 23.1. Achieving the Ministry of Health's (MoH) Priority 2 (P2) target increased from 23% to 87.5%. CONCLUSION: A partnership between Ko Awatea and the radiology department at CMDHB, examining capacity and demand for MRI and using multiple QI techniques, successfully and sustainably reduced the MRI waiting list over a two-year period. The innovative solutions to match capacity to demand may be instructive for other radiology departments, and other waiting list scenarios.

Neocortical Slow Oscillations Implicated in the Generation of Epileptic Spasms.

OBJECTIVE: Epileptic spasms are a hallmark of severe seizure disorders. The neurophysiological mechanisms and the neuronal circuit(s) that generate these seizures are unresolved and are the focus of studies reported here. METHODS: In the tetrodotoxin model, we used 16-channel microarrays and microwires to record electrophysiological activity in neocortex and thalamus during spasms. Chemogenetic activation was used to examine the role of neocortical pyramidal cells in generating spasms. Comparisons were made to recordings from infantile spasm patients. RESULTS: Current source density and simultaneous multiunit activity analyses indicate that the ictal events of spasms are initiated in infragranular cortical layers. A dramatic pause of neuronal activity was recorded immediately prior to the onset of spasms. This preictal pause is shown to share many features with the down states of slow wave sleep. In addition, the ensuing interictal up states of slow wave rhythms are more intense in epileptic than control animals and occasionally appear sufficient to initiate spasms. Chemogenetic activation of neocortical pyramidal cells supported these observations, as it increased slow oscillations and spasm numbers and clustering. Recordings also revealed a ramp-up in the number of neocortical slow oscillations preceding spasms, which was also observed in infantile spasm patients. INTERPRETATION: Our findings provide evidence that epileptic spasms can arise from the neocortex and reveal a previously unappreciated interplay between brain state physiology and spasm generation. The identification of neocortical up states as a mechanism capable of initiating epileptic spasms will likely provide new targets for interventional therapies. ANN NEUROL 2021;89:226-241.

Kv4.2 is a locus for PKC and ERK/MAPK cross-talk.

Transient outward K+ currents are particularly important for the regulation of membrane excitability of neurons and repolarization of action potentials in cardiac myocytes. These currents are modulated by PKC (protein kinase C) activation, and the K+- channel subunit Kv4.2 is a major contributor to these currents. Furthermore, the current recorded from Kv4.2 channels expressed in oocytes is reduced by PKC activation. The mechanism underlying PKC regulation of Kv4.2 currents is unknown. In the present study, we determined that PKC directly phosphorylates the Kv4.2 channel protein. In vitro phosphorylation of the intracellular N- and C-termini of Kv4.2 GST (glutathione transferase) tagged fusion protein revealed that the C-terminal of Kv4.2 was phosphorylated by PKC, whereas the N-terminal was not. Amino acid mapping and site-directed mutagenesis revealed that the phosphorylated residues on the Kv4.2 C-terminal were Ser447 and Ser537. A phospho-site-specific antibody showed that phosphorylation at the Ser537 site was increased in the hippocampus in response to PKC activation. Surface biotinylation experiments revealed that mutation to alanine of both Ser447 and Ser537 in order to block phosphorylation at both of the PKC sites increased surface expression compared with wild-type Kv4.2. Electrophysiological recordings of the wild-type and both the alanine and aspartate mutant Kv4.2 channels expressed with KChIP3 (Kv4 channel-interacting protein 3) revealed no significant difference in the half-activation or half-inactivation voltage of the channel. Interestingly, Ser537 lies within a possible ERK (extracellular-signal-regulated kinase)/MAPK (mitogen-activated protein kinase) recognition (docking) domain in the Kv4.2 C-terminal sequence. We found that phosphorylation of Kv4.2 by PKC enhanced ERK phosphorylation of the channel in vitro. These findings suggest the possibility that Kv4.2 is a locus for PKC and ERK cross-talk.