CP-036 evaluation of outpatient clinic letters for medication errors

Background - It is well recognised that errors are more likely to occur during transitions of care, especially medicines errors. Clinic letters are used as a communication tool during a transition from hospital (outpatient clinics) to primary care (general practitioners). Little is known about medicines errors in clinic letters, as previous studies in this area have focused on medicines errors in inpatient or outpatient prescriptions. Published studies concerning clinic letters largely focus on perceptions of patients or general practitioners in respect to overall quality. Purpose - To investigate medicines errors contained in outpatient clinic letters generated by prescribers within the Neurology Department of a specialist paediatric hospital in the UK.Materials and methods - Single site, retrospective, cross-sectional review of 100 clinic letters generated during March–July 2013 in response to an outpatient consultation. Clinic letters were conveniently selected from the most recent visit of each patient. An evaluation tool with a 10-point scale, where 10 was no error and 0 was significant error, was developed and refined throughout the study to facilitate identification and characterisation of medicines errors. The tool was tested for a relationship between scores and number of medicines errors using a regression analysis.Results - Of 315 items related to neurology mentioned within the letters, 212 items were associated with 602 errors. Common missing information was allergy (97%, n = 97), formulation (60.3%, n = 190), strength/concentration (59%, n = 186) and weight (53%, n = 53). Ninety-nine letters were associated with at least one error. Scores were in range of 4–10 with 42% of letters scored as 7. Statistically significant relationships were observed between scores and number of medicines errors (R2 = 0.4168, p < 0.05) as well as between number of medicines and number of drug-related errors (R2 = 0.9719, p < 0.05). Conclusions - Nearly all clinic letters were associated with medicines errors. The 10-point evaluation tool may be a useful device to categorise clinic letter errors.

The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility

The interplay between long-term potentiation and long-term depression (LTD) is thought to be involved in learning and memory formation. One form of LTD expressed in the hippocampus is initiated by the activation of the group 1 metabotropic glutamate receptors (mGluRs). Importantly, mGluRs have been shown to be critical for acquisition of new memories and for reversal learning, processes that are thought to be crucial for cognitive flexibility. Here we provide evidence that MAPK-activated protein kinases 2 and 3 (MK2/3) regulate neuronal spine morphology, synaptic transmission and plasticity. Furthermore, mGluR-LTD is impaired in the hippocampus of MK2/3 double knockout (DKO) mice, an observation that is mirrored by deficits in endocytosis of GluA1 subunits. Consistent with compromised mGluR-LTD, MK2/3 DKO mice have distinctive deficits in hippocampal-dependent spatial reversal learning. These novel findings demonstrate that the MK2/3 cascade plays a strategic role in controlling synaptic plasticity and cognition. © 2014 Macmillan Publishers Limited. All rights reserved.

Activity-regulated cytoskeleton-associated protein controls AMPAR endocytosis through a direct interaction with clathrin-adaptor protein 2

The activity-regulated cytoskeleton-associated (Arc) protein controls synaptic strength by facilitating AMPA receptor (AMPAR) endocytosis. Here we demonstrate that Arc targets AMPAR to be internalized through a direct interaction with the clathrin-adaptor protein 2 (AP-2). We show that Arc overexpression in dissociated hippocampal neurons obtained from C57BL/6 mouse reduces the density of AMPAR GluA1 subunits at the cell surface and reduces the amplitude and rectification of AMPAR-mediated miniature-EPSCs (mEPSCs). Mutations of Arc, that prevent the AP-2 interaction reduce Arc-mediated endocytosis of GluA1 and abolish the reduction in AMPAR-mediated mEPSC amplitude and rectification. Depletion of the AP-2 subunit µ2 blocks the Arc-mediated reduction in mEPSC amplitude, an effect that is restored by reintroducing µ2. The Arc-AP-2 interaction plays an important role in homeostatic synaptic scaling as the Arc-dependent decrease in mEPSC amplitude, induced by a chronic increase in neuronal activity, is inhibited by AP-2 depletion. These data provide a mechanism to explain how activity-dependent expression of Arc decisively controls the fate of AMPAR at the cell surface and modulates synaptic strength, via the direct interaction with the endocytic clathrin adaptor AP-2.