A series of substituted angular benzophenazines were prepared using a new synthetic route via a novel regiocontrolled condensation of 1,2-naphthoquinones and 2,3-diaminobenzoic acids. The synthesis and biological activity of this new series of substituted 8,9-benzo[a]phenazine carboxamide systems are described. The analogues were evaluated against the H69 parental human small cell lung carcinoma cell line and H69/LX4 resistant cell line which overexpresses P-glycoprotein. Selected analogues were evaluated against the COR-L23 parental human non small cell lung carcinoma cell line and the COR-L23/R resistant cell line which overexpresses multidrug resistance protein. This series of novel angular benzophenazines were potent cytotoxic agents in these cell lines and may be able to circumvent multidrug resistance mechanisms which result in the lack of efficacy of many drugs in cancer chemotherapy. These compounds show dual inhibition of topoisomerase I and topoisomerase II and thus target two key enzymes responsible for the topology of DNA that are active at different points in the cell cycle. The introduction of chirality into the carboxamide side chain of these novel benzophenazine carboxamides has resulted in the discovery of a potent enantiospecific series of cytotoxic agents, exemplified by 4-methoxy-benzo[a]phenazine-11-carboxylic acid (2-(dimethylamino)-1-(R)-methyl-ethyl)-amide, XR11576 ((R)-4j' '). In vivo activity has been demonstrated for 4-methoxy-benzo[a]phenazine-11-carboxylic acid (2-(dimethylamino)-1-(R)-methyl-ethyl)-amide, XR11576, after intravenous administration to female mice, and this compound has been selected as a development candidate for further evaluation.

The project sought to undertake a clinical audit of triage practice to evaluate the adherence of practice to evidence-based guidelines. The project has provided strong support for the implementation of a formal nursing role to support the care of waiting room patients, and act as a second triage nurse during periods of high activity. The physical triage environment has been identified as a barrier to optimal adherence to evidence-based practice guidelines. Using effective communication to manage the waiting experience of patients can have positive benefits for both patients and staff.

Purpose: Nurses provide care at each phase of the complex, perioperative pathway and are well placed to identify areas of care requiring investigation in randomized controlled trials. Yet, currently, the scope of nurse-led randomized controlled trials conducted within the perioperative setting are unknown. This scoping review aims to identify areas of perioperative care in which nurse-led randomized controlled trials have been conducted, to identify issues impacting upon the quality of these trials and identify gaps for future investigation. Methods: This scoping review was conducted in reference to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. Searches were conducted in PubMed, Embase, Cumulative Index for Nursing and Allied Health Literature and the Cochrane Central Register of Controlled Trials, with a date range of 2014-19. Sources of unpublished literature included Open Grey, and ProQuest Dissertation and Theses, Clinical Trials.gov and the Australian and New Zealand Clinical Trials Registry. After title and abstract checking, full-text retrieval and data extraction, studies were appraised using the Joanna Briggs Institute Critical Appraisal Checklists for randomized controlled trials. Data were synthesized according to the main objectives. Key information was tabulated. Results: From the 86 included studies, key areas where nurses have led randomized controlled trials include patient or caregiver anxiety; postoperative pain relief; surgical site infection prevention: patient and caregiver knowledge; perioperative hypothermia prevention; postoperative nausea and vomiting; in addition to other diverse outcomes. Issues impacting upon quality (including poorly reported randomization), and gaps for future investigation (including a focus on vulnerable populations), are evident. Conclusion: Nurse-led randomized controlled trials in the perioperative setting have focused on key areas of perioperative care. Yet, opportunities exist for nurses to lead experimental research in other perioperative priority areas and within different populations that have been neglected, such as in the population of older adults undergoing surgery.

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