Feasibility of direct discharge from the coronary/intermediate care unit after acute myocardial infarction

AbstractOBJECTIVESThis investigation was designed to determine the feasibility and cost-effectiveness of direct discharge from the coronary/intermediate care unit (CICU) in 497 consecutive patients with an acute myocardial infarction (AMI).BACKGROUNDAlthough patients with an AMI are traditionally treated in the CICU followed by a period on the medical ward, the latter phase can likely be incorporated within the CICU.METHODSAll patients were considered for direct discharge from the CICU with appropriate patient education. The 6-week postdischarge course was evaluated using a structured questionnaire by a telephone interview.RESULTSThere were 497 patients (men = 353; women = 144; age 63.5 ± 0.6 years) in the study, with 29 in-hospital deaths and a further 11 deaths occurring within 6 weeks of discharge. The mode length of CICU stay was 4.0 days (mean 5.1 ± 0.2 days): 1 to 2 (12%), 3 (19%), 4 (21%), 5 (14%), 6 to 7 (19%) and ≥7 (15%) days, respectively with 87.2% discharged home directly. Of the 425 patients surveyed, 119 (28.0%) indicated that they had made unscheduled return visits (URV) to a hospital or physician’s office: 10.6% to an emergency room, 9.4% to a physician’s office and 8.0% readmitted to a hospital. Of these URV, only 14.3% occurred within 48 h of discharge. Compared to historical controls, the present management strategy resulted in a cost savings of Cdn. $4,044.01 per patient.CONCLUSIONSDirect discharge from CICU is a feasible and safe strategy for the majority of patients that results in considerable savings

Fexinidazole – A New Oral Nitroimidazole Drug Candidate Entering Clinical Development for the Treatment of Sleeping Sickness

This article describes the preclinical profile of fexinidazole, a new drug candidate with the potential to become a novel, oral, safe and effective short-course treatment for curing both stage 1 and 2 human African trypanosomiasis and replace the old and highly problematic treatment modalities available today. Fexinidazole is orally available and rapidly metabolized in two metabolites having equivalent biological activity to the parent and contributing significantly to the in vivo efficacy in animal models of both stage 1 and 2 HAT. Animal toxicology studies indicate that fexinidazole has an excellent safety profile, with no particular issues identified. Fexinidazole is a 5-nitroimidazole and, whilst it is Ames-positive, it is devoid of any genetic toxicity in mammalian cells and therefore does not pose a genotoxic risk for use in man. Fexinidazole, which was rediscovered through a process of compound mining, is the first new drug candidate for stage 2 HAT having entered clinical trials in thirty years, and has the potential to revolutionize therapy of this fatal disease at a cost that is acceptable in the endemic regions

Monoamine oxidase-dependent endoplasmic reticulum-mitochondria dysfunction and mast cell degranulation lead to adverse cardiac remodeling in diabetes.

Monoamine oxidase (MAO) inhibitors ameliorate contractile function in diabetic animals, but the mechanisms remain unknown. Equally elusive is the interplay between the cardiomyocyte alterations induced by hyperglycemia and the accompanying inflammation. Here we show that exposure of primary cardiomyocytes to high glucose and pro-inflammatory stimuli leads to MAO-dependent increase in reactive oxygen species that causes permeability transition pore opening and mitochondrial dysfunction. These events occur upstream of endoplasmic reticulum (ER) stress and are abolished by the MAO inhibitor pargyline, highlighting the role of these flavoenzymes in the ER/mitochondria cross-talk. In vivo, streptozotocin administration to mice induced oxidative changes and ER stress in the heart, events that were abolished by pargyline. Moreover, MAO inhibition prevented both mast cell degranulation and altered collagen deposition, thereby normalizing diastolic function. Taken together, these results elucidate the mechanisms underlying MAO-induced damage in diabetic cardiomyopathy and provide novel evidence for the role of MAOs in inflammation and inter-organelle communication. MAO inhibitors may be considered as a therapeutic option for diabetic complications as well as for other disorders in which mast cell degranulation is a dominant phenomenon