(C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;106:1626-1633)”
“Several lines of evidence point to the modification of firing patterns and of synchronization due to gap junctions (GJs) as having a role in the establishment of epileptiform activity (EA). However, previous studies consider GJs as ohmic resistors, ignoring the effects of intense variations

in ionic concentration known to occur during seizures. In addition to GJs, extracellular potassium is regarded as a further important factor involved in seizure initiation and sustainment. To analyze how these two mechanisms act together to shape firing and synchronization, Quisinostat we use a detailed computational model for in vitro high-K(+) and low-Ca(2+) nonsynaptic EA. The model permits us to explore the modulation of electrotonic interactions under ionic concentration changes caused by electrodiffusion in the extracellular space, altered by tortuosity. In addition, we investigate the special case of null GJ current. Increased electrotonic MDV3100 Endocrinology & Hormones inhibitor interaction alters bursts and action potential frequencies, favoring synchronization. The particularities of pattern changes depend on the tortuosity and array size.

Extracellular potassium accumulation alone modifies firing and synchronization when the GJ coupling is null.”
“Background: Health IT can play a major role in improving patient safety. Computerized physician order entry with decision support can alert providers to potential prescribing errors. However, too many alerts can result in providers ignoring and overriding clinically important ones.\n\nObjective: To evaluate the appropriateness of providers’ drug-drug interaction (DDI) alert overrides, the reasons why they chose to override these alerts, and what actions they took as a consequence of the alert.\n\nDesign: A cross-sectional, observational study of DDI alerts generated over a three-year period between January 1st, 2009, and December 31st, 2011.\n\nSetting: Primary care practices affiliated with two Harvard teaching hospitals. The DDI alerts were screened to minimize the number of clinically

unimportant warnings.\n\nParticipants: A total of 24,849 DDI alerts selleck kinase inhibitor were generated in the study period, with 40% accepted. The top 62 providers with the highest override rate were identified and eight overrides randomly selected for each (a total of 496 alert overrides for 438 patients, 3.3% of the sample).\n\nResults: Overall, 68.2% (338/496) of the DDI alert overrides were considered appropriate. Among inappropriate overrides, the therapeutic combinations put patients at increased risk of several specific conditions including: serotonin syndrome (21.5%, n=34), cardiotoxicity (16.5%, n=26), or sharp falls in blood pressure or significant hypotension (28.5%, n=45). A small number of drugs and DDIs accounted for a disproportionate share of alert overrides.