Managing complex palliative wounds: an interactive educational approach for district nurses.

Complex palliative wounds, although uncommon, are extremely distressing for patients because of their associated symptoms. Managing these symptoms presents significant challenges to clinicians. As the majority of these patients will be managed at home, district nurses will be the main providers of care. The quality of the literature in this field is limited due to the small number of patients presenting with these wounds and the difficulties associated with researching issues within palliative care. However, the literature available identifies that community nurses would value greater education in managing these wounds because the accepted wound healing theories and management strategies do not apply. This underpins the rationale for developing an educational resource to provide district nurses with current, evidence-based information to support their wound-management decisions in caring for this patient group. This paper reports the development, through an action research work-based project, of such an interactive educational package.

A pilot feasibility trial of allocation of freshest available red blood cells versus standard care in critically ill patients.

BACKGROUND: Prolonged storage of red blood cells (RBCs) may increase posttransfusion adverse events in critically ill patients. We aimed to evaluate in intensive care unit (ICU) patients 1) the feasibility of allocating freshest available compatible RBCs versus standard care and 2) the suitability of this approach in the design of a large randomized controlled trial (RCT). STUDY DESIGN AND METHODS: Eligible patients from two adult ICUs were randomly assigned to receive either the freshest available compatible RBCs or the standard care (the oldest compatible available RBCs) for all transfusions during their ICU stay. Study group allocation was concealed from patients and bedside clinicians, but the transfusion service was unblinded. The study endpoints were the feasibility of the study procedures, including success of the ICU Web randomization, the ICU staff blinding, and the correct delivery of the RBC units by the transfusion service in accordance with the allocated study group. In addition, we measured the difference in age of RBC units between the two groups. RESULTS: During a 3-month period, 177 RBC units were delivered to 51 patients. All study procedures, including randomization, blinding, and delivery of blood in accordance with the study group were successful. The mean (±SD) of the mean age of the RBC received by each patient was lower in the "fresher blood" group compared with the standard care group (12.1 [±3.8] days vs. 23 [±8.4] days; p<0.001). CONCLUSION: Randomized delivery of the freshest available RBCs versus standard care to ICU patients who were prescribed transfusion for clinical reasons is feasible, with a clinically relevant degree of storage duration separation achievable between the two study groups. These findings support the feasibility of a future large pragmatic RCT.

A feasibility study of a randomised controlled trial to examine the impact of the ABCDE bundle on quality of life in ICU survivors.

BACKGROUND: Early rehabilitation has been found to prevent delirium and weakness that can hamper the recovery of intensive care unit (ICU) survivors. Integrated clinical practice guidelines for managing patient pain, agitation and delirium (PAD) have been developed. The Awakening and Breathing Coordination, Delirium monitoring/management, and Early exercise/mobility (ABCDE) bundle provides a strategy to implement PAD guidelines into everyday clinical practice. However, there is limited evidence on the effectiveness of the ABCDE bundle in the literature.The purpose of this study was to evaluate the feasibility of conducting a full-scale randomised controlled trial comparing the ABCDE bundle to standard care in an ICU. Trial feasibility was defined as the successful recruitment and retention of trial participants, adherence to the intervention, identification of barriers to the intervention, and the rigorous collection of outcome data. METHODS: A prospective, single-centre, randomised controlled feasibility study was conducted. Thirty adult mechanically ventilated participants were recruited from an eight-bed ICU in south east Queensland, Australia, between April 2015 and December 2015. Participants were randomised to receive either the ABCDE bundle or standard routine management. The ABCDE bundle integrated prescribed awakening and breathing trials, delirium monitoring and management, and prescribed exercise and mobility regimes. Feasibility outcomes measured included recruitment and retention rates, intervention fidelity, and the feasibility of participant outcome data collection. Outcome measurement assessors were blinded to participant assignment. It was not possible to blind the research team or the participant to group assignment. RESULTS: In total, 30 (81.1%) of 37 eligible participants consented and were randomised to the intervention group (n = 15) or the control group (n = 15). Of these, 23 (76.6%) participants successfully completed the 90-day post discharge assessment. A lengthy recruitment period of 8 months was related to overly stringent inclusion and exclusion criteria. Intervention adherence exceeded defined success rates with participation in awakening and breathing trials, delirium monitoring and exercise interventions performed on 80.2, 97.4 and 90.2% of ventilated days respectively. Outcome assessments were successfully and accurately performed at ICU and hospital discharge and 90-day post hospital discharge. Intervention participants were deemed to be delirious on 39.6% of mechanically ventilated days indicating a requirement for a scripted regime to prevent delirium. CONCLUSIONS: With minor adjustment of inclusion and exclusion criteria, the inclusion of delirium management protocols, and encouragement of family engagement and involvement, a large-scale definitive randomised controlled trial to test the impact of the ABCDEF bundle will be feasible. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry 12614000763640 Date registered 17/08/2014.

An ENU mutagenesis screen identifies novel and known genes involved in epigenetic processes in the mouse.

BACKGROUND: We have used a sensitized ENU mutagenesis screen to produce mouse lines that carry mutations in genes required for epigenetic regulation. We call these lines Modifiers of murine metastable epialleles (Mommes). RESULTS: We report a basic molecular and phenotypic characterization for twenty of the Momme mouse lines, and in each case we also identify the causative mutation. Three of the lines carry a mutation in a novel epigenetic modifier, Rearranged L-myc fusion (Rlf), and one gene, Rap-interacting factor 1 (Rif1), has not previously been reported to be involved in transcriptional regulation in mammals. Many of the other lines are novel alleles of known epigenetic regulators. For two genes, Rlf and Widely-interspaced zinc finger (Wiz), we describe the first mouse mutants. All of the Momme mutants show some degree of homozygous embryonic lethality, emphasizing the importance of epigenetic processes. The penetrance of lethality is incomplete in a number of cases. Similarly ,abnormalities in phenotype seen in the heterozygous individuals of some lines occur with incomplete penetrance. CONCLUSIONS: Recent advances in sequencing enhance the power of sensitized mutagenesis screens to identify the function of previously uncharacterized factors and to discover additional functions for previously characterized proteins. The observation of incomplete penetrance of phenotypes in these inbred mutant mice, at various stages of development, is of interest. Overall, the Momme collection of mouse mutants provides a valuable resource for researchers across many disciplines.

A forward genetic screen identifies eukaryotic translation initiation factor 3, subunit H (eIF3h), as an enhancer of variegation in the mouse.

We have used a forward genetic screen to identify genes required for transgene silencing in the mouse. Previously these genes were found using candidate-based sequencing, a slow and labor-intensive process. Recently, whole-exome deep sequencing has accelerated our ability to find the causative point mutations, resulting in the discovery of novel and sometimes unexpected genes. Here we report the identification of translation initiation factor 3, subunit H (eIF3h) in two modifier of murine metastable epialleles (Mommes) lines. Mice carrying mutations in this gene have not been reported previously, and a possible involvement of eIF3h in transcription or epigenetic regulation has not been considered.

Increased risk for aplastic anemia and myelodysplastic syndrome in individuals lacking glutathione S-transferase genes.

BACKGROUND: Aplastic anemia (AA) and myelodysplastic syndrome (MDS) are marrow failure states that may be associated with chromosomal instability. An absence of the glutathione S-transferase (GST) enzyme may genetically predispose individuals to AA or MDS. PROCEDURE AND RESULTS: To test this hypothesis, we determined the GSTM1 and GSTT1 genotypes in a total of 196 patients using multiplex PCR. The GSTT1 null genotype was found to be overrepresented in Caucasian, Asian, and Hispanic patients with either AA or MDS. We confirmed a difference in the expected frequency of the GSTM1 null genotype in Caucasian MDS patients. The double null GSTM1/GSTT1 genotype was also overrepresented in Caucasian AA and MDS patients. In our population, 26% of AA patients and 40% of MDS patients had a chromosomal abnormality identified by karyotype or FISH analyses for chromosomes 7 and 8. Patients with AA and the GSTT1 null genotype had an increased frequency of chromosomal abnormalities (P = 0.003). CONCLUSION: There seems to be an increased risk for AA and MDS in individuals lacking GSTT1 or both GSTM1/GSTT1.

Genomic instability in bone marrow failure syndromes.

Aneuploidy is frequently seen in leukemia and myelodysplasia (MDS) but was thought to be uncommon in aplastic anemia (AA). We examined marrow cells from 96 unselected patients with bone marrow failure syndromes to assess the frequency of undetected aneuploidy for chromosomes 7 and 8 by fluorescence in situ hybridization (FISH) as compared to routine cytogenetic analysis. Twenty-eight percent (27/96) of patients had an abnormal karyotype. FISH identified an additional 27 patients with undetected monosomy 7 or trisomy 8. Those patients with undetected monosomy 7 generally had a poor clinical outcome, suffering from lack of response to medical therapy or early death. In one AA/MDS patient with normal cytogenetics, FISH identified a large population of monosomy 7 cells, which clearly heralded a clinical relapse. In another patient, FISH studies were used to delineate instability of chromosome 8, with apparent disease progression from AA to MDS. We conclude that undetected aneuploidy exists in marrow cells of a significant percentage of patients with bone marrow failure syndromes.