The effect of medication reconciliation in elderly patients at hospital discharge.

Objective To assess the impact of medication reconciliation interventions on medication error rates when elderly patients are discharged from hospital to community care or nursing homes.Setting Elderly patients (>65 years) living in nursing homes or in their own homes with care provided by the community nursing system. Method All medical records containing information on drug treatment were collected from hospital departments, the community care service and GPs. We then identified if there were any changes in the transfer of information i.e. if the drugs were not the same as before the transfer. Two different persons independently evaluated all information about the patients' drugs to identify medication errors for three different time periods. During all three periods structured discharge information was used. In period 2, electronic medication lists were introduced and in period 3 we introduced specific routines and support by a clinical pharmacist to ensure prescription in the specific medication dispensing system (ApoDos). Asymptotic Linear by-Linear Association Test was used to compare number of medication errors in period 1, 2 and 3 respectively. Main outcome measure Number of medication errors per patient. Results A total of 123 patients were evaluated at discharge. For the 109 patients using the ApoDos system, there were significant differences in the number of medication errors between period 1 and 3 (P = 0.048), period 2 and 3 (P = 0.037 but not between period 1 and 2 (P = 0.41). The mean numbers of errors were 1.5, 1.1 and 0.5 for period 1, 2 and 3 respectively. The 14 patients not using the ApoDos system had on average 0.4 errors per patient. Among the 58 patients with medication errors, 34 were evaluated as having low clinical risk, 22 moderate, and 2 high clinical risk. Conclusion Medication errors are still common when elderly patients are transferred from hospital to community/primary care. The main risk factor seems to be the specific medication dispensing system (ApoDos) or rather the process on how to use it. When this system was supported by clinical pharmacists, the error rate dropped to the same level as for patients without ApoDos

Apolipoprotein D synthesis progressively increases in frontal cortex during human lifespan

Apolipoprotein D (apo D) is a lipocalin present in the nervous system that may be related to processes of reinnervation, regeneration and neuronal cell protection. In the other way, apo D expression has been correlated, in some brain regions, with normal aging and neurodegenerative diseases. To elucidate the regional and cellular expression of apo D in normal human brain during aging, we performed a detailed and extensive study in samples of post-mortem human cerebral cortices. To achieve this study, slot blot techniques, for protein and mRNA, as well as immunohistochemistry and hybridohistochemistry methods were used. A positive correlation for apo D expression with aging was found; furthermore, mRNA levels, as well as the protein ones, were higher in the white than in the grey matter. Immunohistochemistry and non-isotopic HIS showed that apo D is synthesized in both neurons and glial cells. Apo D expression is notorious in oligodendrocytes but with aging the number of neurons that synthesize apo D is increased. Our results indicate that apo D could play a fundamental role in central nervous system aging and in the reduction of products derivated from lipid peroxidation. The increment in the expression of apo D with aging can be included in a global mechanism of cellular protection to prevent the deleterious effects caused by aging

NMDA receptors are selectively partitioned into complexes and supercomplexes during synapse maturation

How neuronal proteomes self-organize is poorly understood because of their inherent molecular and cellular complexity. Here, focusing on mammalian synapses we use blue-native PAGE and ‘gene-tagging’ of GluN1 to report the first biochemical purification of endogenous NMDA receptors (NMDARs) directly from adult mouse brain. We show that NMDARs partition between two discrete populations of receptor complexes and B1.5MDa supercomplexes. We tested the assembly mechanism with six mouse mutants, which indicates a tripartite requirement of GluN2B, PSD93 and PSD95 gate the incorporation of receptors into B1.5MDa supercomplexes, independent of either canonical PDZ-ligands or GluN2A. Supporting the essential role of GluN2B, quantitative gene-tagging revealed a fourfold molar excess of GluN2B over GluN2A in adult forebrain. NMDAR supercomplexes are assembled late in postnatal development and triggered by synapse maturation involving epigenetic and activity-dependent mechanisms. Finally, screening the quaternary organization of 60 native proteins identified numerous discrete supercomplexes that populate the mammalian synapse

Gene Expression Changes and Brain Plasticity after Experimental Stroke

Stroke is the most common life-threatening neurological disease and ranks as the third leading cause of death in major industrialized countries. It is also the leading cause of serious long-term disability and about sixty percent of survivors have disabilities in their extremities. Recovery of certain neurological functions occurs over time, which has been attributed to endogenous restorative processes in areas adjacent and remote from the infarct area. The area adjacent to infarct, the peri-infarct area, shows activation of processes pertinent for recovery such as enhanced cellular excitability and axonal sprouting. The major objective of this thesis has been to unravel some aspects of functional recovery following stroke. In Paper I, we undertook a comprehensive investigation of gene expression changes in the peri-infarct area during the first 24 h after insult using large-scale array technology. Several genes associated with tissue regeneration and recovery, were activated early after the ischemic insult. In particular, we identified genes related to lipid transport and myelin formation as well as genes involved in synaptic plasticity. This suggests that parallel to cell death signaling and ensuing cell death in severely injured areas, repair processes are induced in the adjacent surviving areas. In Paper II and II, we characterized expression of transcriptional regulators/effectors most likely implicated in adaptation/stress response of the peri-infarct area. The second part of the thesis focused on the long-term recovery period (0-30 days) following stroke. In Paper IV, we investigated the role of Apolipoprotein D, a transport protein known to be important for lipid trafficking. ApoD accumulated along the rim of the infarct during the first week of recovery and was localized to oligodendrocytes. We believe that this expression is associated with regeneration of the peri-infarct area and ApoD may function as a lipid carrier providing myelinating oligodendrocytes with cholesterol for axonal regeneration. Further, housing animals in an enriched setting during the post-ischemic period elicited increased levels of ApoD and this was associated with an improved functional recovery. In Paper V, we showed that administration of a receptor ligand, initiated two days following insult, enhanced functional recovery. The mechanisms of this recovery enhancing effects were attributed to stimulation of axonal outgrowth and possibly regulation of lipid transport in the peri-infarct area. The last two studies reveal novel aspects of recovery by emphasizing the importance of lipid trafficking for formation of new connections of the brain. Overall, this thesis shows that the injured brain activates repair processes early after an ischemic insult and that these events can be stimulated by either pharmacology and/or enriched environment. Delaying commencement of pharmacological treatment for days after injury still results in an improvement in functional outcome. This finding together with other reports strongly argue that the therapeutic time window after stroke is much more extensive than previously believed. Eligible future stroke therapies must consider beyond the acute phase of cell death and focus on enhancement of post-injury plasticity