Train-of-four (TOF) monitoring is recommended in published guidelines during use of continuous-infusion neuromuscular blocking agents (NMB) in the intensive care unit (ICU). To test that recommendation, dual protocols were established in a medical ICU after intensive nursing education. Paralyzed patients received either TOF monitoring with a goal of three twitches or best clinical assessment while receiving atracurium by continuous infusion. Demographics and mean duration of paralysis of 20 patients in the TOF group were no different than that of the 16 patients in the best clinical assessment group. Although most patients demonstrated atracurium tolerance over time, there was no difference between groups in total mg (+/- SEM) infused (10,460 +/- 2,409 versus 9,201 +/- 3,237) or mean microgram/kg/min (15.2 +/- 1.5 versus 12.0 +/- 1.1). The time to clinical recovery was no different between groups (50 +/- 10 versus 45 +/- 12 min). Two complications occurred in the TOF group, with pulmonary emboli despite prophylaxis and an unrecognized cerebrovascular accident in one patient each. We conclude that careful titration of NMB using clinical bedside markers should remain the standard of care with these drugs.
Tissue fibrosis, an accumulation of extracellular matrix proteins such as collagen, accompanies cardiac ageing in humans and this is linked to an increased risk of cardiac failure. The mechanisms driving age-related tissue fibrosis and cardiac dysfunction are unclear, yet clinically important. Drosophila is amenable to the study of cardiac ageing as well as collagen deposition; however it is unclear whether collagen accumulates in the ageing Drosophila heart.This work examined collagen deposition and cardiac function in ageing Drosophila, in the context of reduced expression of collagen-interacting protein SPARC (Secreted Protein Acidic and Rich in Cysteine) an evolutionarily conserved protein linked with fibrosis. Heart function was measured using high frame rate videomicroscopy. Collagen deposition was monitored using a fluorescently-tagged collagen IV reporter (encoded by the Viking gene) and staining of the cardiac collagen, Pericardin.The Drosophila heart accumulated collagen IV and Pericardin as flies aged. Associated with this was a decline in cardiac function. SPARC heterozygous flies lived longer than controls and showed little to no age-related cardiac dysfunction. As flies of both genotypes aged, cardiac levels of collagen IV (Viking) and Pericardin increased similarly. Over-expression of SPARC caused cardiomyopathy and increased Pericardin deposition.The findings demonstrate that, like humans, the Drosophila heart develops a fibrosis-like phenotype as it ages. Although having no gross impact on collagen accumulation, reduced SPARC expression extended Drosophila lifespan and cardiac health span. It is proposed that cardiac fibrosis in humans may develop due to the activation of conserved mechanisms and that SPARC may mediate cardiac ageing by mechanisms more subtle than gross accumulation of collagen.
Within the limits of the assays, relative potencies of the three preparations appeared to be approximately equivalent for both topical and systemic effect when dose was expressed in micrograms. Relative potency per puff is therefore approximately proportional to the dose delivered. This method has potential for evaluation of relative potency of newer inhaled corticosteroids and the relative advantage of alternative delivery systems.
Palliative care is one of the newer health specialties and continues to mature. While there has been remarkable progression of clinical skills and education, there has been a lack of focus on palliative care interdisciplinary leadership or development of leadership skills. This article highlights the importance of interdisciplinary palliative leadership within the 5 realms of clinical practice, research, education, policy/advocacy, and administration. A definition of leadership is offered and discussion of successful leadership skills is described. A current review of leadership opportunities is provided.
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