Single-Dose Intravenous Toxicity Study of IRDye 800CW in Sprague-Dawley Rats

Objective: Fluorophore-labeled contrast imaging agents are moving toward clinical use for a number of applications. The near-infrared dye IRDye 800CW is frequently used in its N-hydroxysuccinamide (NHS) ester form for labeling these agents. Following conjugation or breakdown of a labeled ligand, excess NHS ester is converted to the carboxylate form. To prepare for clinical use as a near-infrared fluorophore, a toxicity study was conducted on IRDye 800CW carboxylate. Methods: Male and female Sprague–Dawley rats were given a single intravenous or intradermal administration of IRDye 800CW carboxylate; Indocyanine Green was used as a comparative control. Animals were injected with varying doses of the test and control articles and observed for up to 14 days. Clinical chemistry, hematological, and pharmacokinetic analyses were performed on subgroups of animals. Organs were analyzed for content of the test article. Tissues were analyzed microscopically for pathological changes. Results: Based on hematologic, clinical chemistry, and histopathologic evaluation, single administration of IRDye 800CW carboxylate intravenously at dose levels of 1, 5, and 20 mg/kg or 20 mg/kg intradermally produced no pathological evidence of toxicity. Conclusion: A dose of 20 mg/kg was identified as the no observed adverse effect level following IV or ID routes of administration of IRDye 800CW

Undergraduate training in the care of the acutely ill patient : a literature review

Objective: To characterise the problem of teaching acute care skills to undergraduates and to look for potential solutions. Design: Systematic literature review including Medline, EMBASE, CINAHL. Eligible studies described education and training issues focusing on caring for acutely ill patients. Articles were excluded if they did not address either educational or clinical aspects of acute care and resuscitation. Measurement and results: We identified and reviewed 374 articles focusing on training or clinical aspects of caring for the acutely ill patient. Undergraduates and junior physicians lack knowledge, confidence and competence in all aspects of acute care, including the basic task of recognition and management of the acutely ill patient. There is wide variability both between and within countries regarding the amount of teaching in critical care offered to undergraduate medical students. Many centres are starting to use an integrated approach to acute care teaching, with early exposure to basic life support and clinical skills, coupled with later exposure to more complex acute care topics. Clinical attachments remain a popular method for training in acute care. Acute care courses are increasingly being used to standardise delivery of practical skills and patient management training. Conclusion: The training of healthcare staff in the care of acutely ill patients is suboptimal, adding to patient risk. Improvements in training should start at undergraduate level for maximal effect, should be integrated with postgraduate education, and are likely to enhance current efforts to improve patient safety in acute care