Impact of a computerized physician order entry system on compliance with prescription accuracy requirements.

OBJECTIVE: To assess the change in non-compliant items in prescription orders following the implementation of a computerized physician order entry (CPOE) system named PreDiMed. SETTING: The department of internal medicine (39 and 38 beds) in two regional hospitals in Canton Vaud, Switzerland. METHOD: The prescription lines in 100 pre- and 100 post-implementation patients' files were classified according to three modes of administration (medicines for oral or other non-parenteral uses; medicines administered parenterally or via nasogastric tube; pro re nata (PRN), as needed) and analyzed for a number of relevant variables constitutive of medical prescriptions. MAIN OUTCOME MEASURE: The monitored variables depended on the pharmaceutical category and included mainly name of medicine, pharmaceutical form, posology and route of administration, diluting solution, flow rate and identification of prescriber. RESULTS: In 2,099 prescription lines, the total number of non-compliant items was 2,265 before CPOE implementation, or 1.079 non-compliant items per line. Two-thirds of these were due to missing information, and the remaining third to incomplete information. In 2,074 prescription lines post-CPOE implementation, the number of non-compliant items had decreased to 221, or 0.107 non-compliant item per line, a dramatic 10-fold decrease (chi(2) = 4615; P < 10(-6)). Limitations of the computerized system were the risk for erroneous items in some non-prefilled fields and ambiguity due to a field with doses shown on commercial products. CONCLUSION: The deployment of PreDiMed in two departments of internal medicine has led to a major improvement in formal aspects of physicians' prescriptions. Some limitations of the first version of PreDiMed were unveiled and are being corrected.

Intracortical connectivity of layer VI pyramidal neurons in the somatosensory cortex of normal and barrelless mice.

In mice, barrels in layer IV of the somatosensory cortex correspond to the columnar representations of whisker follicles. In barrelless (BRL) mice, barrels are absent, but functionally, a columnar organization persists. Previously we characterized the aberrant geometry of thalamic projection of BRL mice using axonal reconstructions of individual neurons. Here we proceeded with the analysis of the intracortical projections from layer VI pyramidal neurons, to assess their contribution to the columnar organization. From series of tangential sections we reconstructed the axon collaterals of individual layer VI pyramidal neurons in the C2 barrel column that were labelled with biocytin [controls from normal (NOR) strain, 19 cells; BRL strain, nine cells]. Using six morphological parameters in a cluster analysis, we showed that layer VI neurons in NOR mice are distributed into four clusters distinguished by the radial and tangential extent of their intracortical projections. These clusters correlated with the cortical or subcortical projection of the main axon. In BRL mice, neurons were distributed within the same four clusters, but their projections to the granular and supragranular layers were significantly smaller and their tangential projection was less columnar than in NOR mice. However, in both strains the intracortical projections had a preference for the appropriate barrel column (C2), indicating that layer VI pyramidal cells could participate in the functional columnar organization of the barrel cortex. Correlative light and electron microscopy analyses provided morphometric data on the intracortical synaptic boutons and synapses of layer VI pyramidal neurons and revealed that projections to layer IV preferentially target excitatory dendritic spines and shafts.

Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis.

Hajdu-Cheney syndrome is a rare autosomal dominant skeletal disorder with facial anomalies, osteoporosis and acro-osteolysis. We sequenced the exomes of six unrelated individuals with this syndrome and identified heterozygous nonsense and frameshift mutations in NOTCH2 in five of them. All mutations cluster to the last coding exon of the gene, suggesting that the mutant mRNA products escape nonsense-mediated decay and that the resulting truncated NOTCH2 proteins act in a gain-of-function manner.

Exogenous mRNA delivery and bioavailability in gene transfer mediated by piggyBac transposition.

BACKGROUND: Up to now, the different uptake pathways and the subsequent intracellular trafficking of plasmid DNA have been largely explored. By contrast, the mode of internalization and the intracellular routing of an exogenous mRNA in transfected cells are poorly investigated and remain to be elucidated. The bioavailability of internalized mRNA depends on its intracellular routing and its potential accumulation in dynamic sorting sites for storage: stress granules and processing bodies. This question is of particular significance when a secure transposon-based system able to integrate a therapeutic transgene into the genome is used. Transposon vectors usually require two components: a plasmid DNA, carrying the gene of interest, and a source of transposase allowing the integration of the transgene. The principal drawback is the lasting presence of the transposase, which could remobilize the transgene once it has been inserted. Our study focused on the pharmacokinetics of the transposition process mediated by the piggyBac transposase mRNA transfection. Exogenous mRNA internalization and trafficking were investigated towards a better apprehension and fine control of the piggyBac transposase bioavailability. RESULTS: The mRNA prototype designed in this study provides a very narrow expression window of transposase, which allows high efficiency transposition with no cytotoxicity. Our data reveal that exogenous transposase mRNA enters cells by clathrin and caveolae-mediated endocytosis, before finishing in late endosomes 3 h after transfection. At this point, the mRNA is dissociated from its carrier and localized in stress granules, but not in cytoplasmic processing bodies. Some weaker signals have been observed in stress granules at 18 h and 48 h without causing prolonged production of the transposase. So, we designed an mRNA that is efficiently translated with a peak of transposase production 18 h post-transfection without additional release of the molecule. This confines the integration of the transgene in a very small time window. CONCLUSION: Our results shed light on processes of exogenous mRNA trafficking, which are crucial to estimate the mRNA bioavailability, and increase the biosafety of transgene integration mediated by transposition. This approach provides a new way for limiting the transgene copy in the genome and their remobilization by mRNA engineering and trafficking.

Processo grupal: reflexões de uma equipe de enfermagem

Estudo qualitativo, exploratório-descritivo com o objetivo de analisar o processo grupal de uma equipe de enfermagem do Hospital de Clínicas de Porto Alegre (HCPA), à luz da Teoria de Grupo Operativo de Pichon-Rivière. A coleta de dados ocorreu em 2008, por meio de questionário semiestruturado e grupo focal. Concepção de trabalho em grupo é uma das quatro categorias resultantes do estudo, sendo objeto de abordagem neste artigo. Depreendeu-se que o conhecimento sobre processo grupal necessita ser compartilhado, divulgado e discutido desde a formação acadêmica, no curso de graduação em enfermagem, e desenvolvido ao longo de toda a carreira profissional. À medida que se conhece e consegue identificar os principais indicadores presentes no processo grupal, a equipe pode conduzir-se operativamente, considerando não apenas resultados, mas principalmente o caminho percorrido até o alcance da tarefa, visando à aprendizagem grupal.