Developing an intervention to equip nurses for acute life threatening events (ALTEs) in hospital:a phenomenological approach to healthcare research

Objectives: To understand staff's experiences of acute life threatening events (ALTEs) in a pediatric hospital setting. These data will inform an intervention to equip nurses with clinical and emotional skills for dealing with ALTEs. Method: A mixed design was used in the broader research program; this paper focuses on phenomenon-focused interviews analyzed using interpretative phenomenological analysis (IPA). Results: Emerging themes included staff's relationships with patients and the impact of personhood on their ability to perform competently in an emergency. More experienced nurses described "automatic" competence generated through increased exposure to ALTEs and were able to recognize "fumbling and shaking" as a normal stress response. Designating a role was significant to staff experience of effectiveness. Key to nurses' learning experience was reflection and identifying experiences as "teachable moments." Findings were considered alongside existing theories of self-efficacy, reflective thought, and advocacy inquiry to create an experiential learning intervention involving a series of clinical and role-related scenarios. Conclusion: The phenomenological work facilitated an in-depth reading of experience. It accentuated the importance of exposure to ALTEs giving nurses experiential knowledge to prepare them for the impact of these events. Challenges included bracketing the personhood of child patients, shifting focus to clinical tasks during the pressured demands of managing an ALTE, normalizing the physiological stress response, and the need for a forum and structure for reflection and learning. An intervention will be designed to provide experiential learning and encourage nurses to realize and benefit from their embodied knowledge

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Advanced practice profiles and work activities of nurse navigators: an early-stage evaluation

Background: Effective coordination and integration of care between health care providers is critical to manage complex, chronic medical conditions. Aim: Describe the advanced practice profile and activities of nurse navigators who provide a service for patients with chronic health conditions. Design: An observational study was conducted in four health services, in Queensland, Australia. Methods: In part one, nurse navigators completed a survey incorporating the Advanced Practice Role Delineation tool. In part two, nurse navigators completed a work activity diary, capturing the time spent performing daily activities, modes of communication and referral sources. Findings: Twenty-three and 18 nurse navigators participated in the survey and diary, respectively. Participants were experienced nurses, working full-time. Participants reported spending a great extent of time performing direct comprehensive care, support of systems and education in surveys. The diaries captured a mean of 20 working days per participant, a total of 5,748 work activities. including care of 615 patients. The majority of nurse navigator activities were performed within the direct comprehensive care domain. Communication predominantly occurred with patients, families, hospital health professionals either in person, at a healthcare facility or via phone. Discussion: Our research identified three focus areas of nurse navigator activities: direct comprehensive care, support of systems and education. Further work is required to extend the nurse navigators’ unique contribution to research and publication and professional leadership. Conclusions: This study established baseline knowledge regarding advanced practice profiles and work activities of nurse navigators, which can be utilised to improve current processes and future enhancement of the role

Qualitative insights of patients and carers under the care of nurse navigators

Background: Nurse navigator roles aim to assist patients and their carers with navigating the healthcare system and accessing services to enable them to take a more active role in their own health care. Aim: The aim of this study was to explore patients’ and carers’ experiences of receiving care from a nurse navigator. Methods: This was a qualitative study involving semi-structured interviews with 12 patients (adults and children) and 13 carers receiving care from a nurse navigator in Queensland, Australia. Thematic analysis was conducted. Findings: The nurse navigator was a central contact person for patients and carers within the complex healthcare system. They were described as approachable, available and knowledgeable about the medical condition and the healthcare system, enabling patients to take a more active role in their own healthcare. The navigators played a pivotal role in navigating the seemingly insurmountable obstacles of accessing advice, services, equipment and appointments in a seamless way. However, further work is required to ensure that patients and carers are connected with a nurse navigator earlier in their healthcare journey. Discussion: The nurse navigators’ understanding of the complex healthcare system coupled with their global overview of patients and carers provided the participants with a sense of direction, options and more control over their own healthcare trajectory. Conclusions: The nurse navigator role has the ability to improve the care experience of patients and carers of varying ages and with varying medical conditions as explored in this study

Novel furano analogues of duocarmycin C1 and C2: design, synthesis, and biological evaluation of\u3cem\u3eseco\u3c/em\u3e-iso-Cyclopropylfurano[2,3-\u3cem\u3ee\u3c/em\u3e]indoline (\u3cem\u3eseco\u3c/em\u3e-iso-CFI) and \u3cem\u3eseco\u3c/em\u3e-Cyclopropyltetrahydrofurano[2,3-\u3cem\u3ef\u3c/em\u3e]quinoline (\u3cem\u3eseco\u3c/em\u3e-CFQ) analogues

The design, synthesis and biological evaluation of novel seco-iso-cyclopropylfurano2,3-e]indoline (seco-iso-CFI) and the seco-cyclopropyltetrahydrofurano2,3-f]quinoline (seco-CFQ) analogues of the duocarmycins are described. These novel analogues (4-7) were designed on the premise that the lone pair of electrons on the furano-oxygen atom could enter into conjugation with the isocyclopropylfuranoe]indolone (iso-CFI) alkylating moiety, formed from the loss of HCl in compounds 4-7. The seco-iso-CFI DNA alkylating pharmacophore was synthesized through a well precedented approach of 5-exo-trig aryl radical cyclization with a vinyl chloride. In our studies, in addition to the formation of the seco-iso-CFI product, an equal amount of an unexpected seco-CFQ product was also generated during the radical cyclization reaction. Like CC-1065 and adozelesin, using Taq DNA polymerase stop and thermal cleavage assays, the seco-iso-CFI compounds (4 and 6) and the seco-CFQ compounds (5 and 7) were shown to preferentially alkylate the adenine-N3 position within the minor groove of long stretches of A residues. A MM2 energy optimized molecular model of a 1:1 complex of compound 6 with DNA reveals that the iso-CFI compound fits snugly within the minor groove. Using a MTT based experiment, the cytotoxicity of compounds 4-7 were determined against the growth of murine leukemia (L1210), mastocytoma (P815) and melanoma (B16) cell lines. The concentrations of compounds required to inhibit the growth of these tumor cells by 50% is in the range of 10-ˆ’8M. These compounds were also tested against a panel of human cancer cells by the National Cancer Institute, demonstrating that the compounds exhibited a high level of activity against selected solid tumors. At a concentration of 0.0084μM (based on the IC50 of compound 17 (seco-CBI-TMI) against the growth L1210 cells), while compounds 4 and 17 were toxic against murine bone marrow cells as judged by a colony forming study of freshly isolated murine progenitor hematopoeitic cells, compound 5, a seco-CFQ compound, was significantly less toxic. Flow cytometric analysis of P815 cells that had been incubated for 24h with compounds 4 and 5 at their cytotoxic IC50 concentrations indicated the induction of apoptosis in a large percentage of cells, thereby suggesting that this might be the mechanism by which the iso-CFI compounds kill cells