Bench to bedside: A role for erythropoietin in sepsis

Sepsis is the systemic inflammatory response to infection and can result in multiple organ dysfunction syndrome with associated high mortality, morbidity and health costs. Erythropoietin is a well-established treatment for the anaemia of renal failure due to its anti-apoptotic effects on red blood cells and their precursors. The extra-haemopoietic actions of erythropoietin include vasopressor, anti-apoptotic, cytoprotective and immunomodulating actions, all of which could prove beneficial in sepsis. Attenuation of organ dysfunction has been shown in several animal models and its vasopressor effects have been well characterised in laboratory and clinical settings. Clinical trials of erythropoietin in single organ disorders have suggested promising cytoprotective effects, and while no randomised trials have been performed in patients with sepsis, good quality data exist from studies on anaemia in critically ill patients, giving useful information of its pharmacokinetics and potential for harm. An observational cohort study examining the microvascular effects of erythropoietin is underway and the evidence would support further phase II and III clinical trials examining this molecule as an adjunctive treatment in sepsis

Monitoring sound levels in the intensive care unit: A mixed-methods system development project to optimize design features for a new electronic interface in the healthcare environment.

BACKGROUND: Intensive care units (ICU) are busy round the clock and it is difficult to maintain low sound levels that support patient rest. To help ICU staff manage activities we developed a visual display that monitors and reports sound levels in real-time. This facilitates immediate feedback, encouraging proactive behavior change to limit disturbances. METHODS: Following the principles of user-centered design practices we created our 'user persona' to understand the needs and goals of potential users of the system. We then conducted iterative user testing with current members of the ICU team, primarily using the 'think aloud' method to refine the design and functionality of our novel system. Ethnography evaluated team use of the display. RESULTS: The final design was simple, clear, and efficient, and both functional and aesthetically pleasing for the key user demographic. We identified challenges in the implementation and adoption process that were separate from the 'usability' of the system itself. CONCLUSIONS: Embedding the design process within the core user demographic ensured the final product delivered relevant information for key users, and that this information was intuitive to interpret. Initiating sustainable change is not straightforward. It requires recognition of cultural practices within teams, departments, professions, organizations, and strategies to maximize engagement

Modifiable factors influencing relatives’ decision to offer organ donation: systematic review

Objective To identify modifiable factors that influence relatives’ decision to allow organ donation

ADRIC: Adverse Drug Reactions In Children - a programme of research using mixed methods

Aims To comprehensively investigate the incidence, nature and risk factors of adverse drug reactions (ADRs) in a hospital-based population of children, with rigorous assessment of causality, severity and avoidability, and to assess the consequent impact on children and families. We aimed to improve the assessment of ADRs by development of new tools to assess causality and avoidability, and to minimise the impact on families by developing better strategies for communication. Review methods Two prospective observational studies, each over 1 year, were conducted to assess ADRs in children associated with admission to hospital, and those occurring in children who were in hospital for longer than 48 hours. We conducted a comprehensive systematic review of ADRs in children. We used the findings from these studies to develop and validate tools to assess causality and avoidability of ADRs, and conducted interviews with parents and children who had experienced ADRs, using these findings to develop a leaflet for parents to inform a communication strategy about ADRs. Results The estimated incidence of ADRs detected in children on admission to hospital was 2.9% [95% confidence interval (CI) 2.5% to 3.3%]. Of the reactions, 22.1% (95% CI 17% to 28%) were either definitely or possibly avoidable. Prescriptions originating in the community accounted for 44 out of 249 (17.7%) of ADRs, the remainder originating from hospital. A total of 120 out of 249 (48.2%) reactions resulted from treatment for malignancies. Off-label and/or unlicensed (OLUL) medicines were more likely to be implicated in an ADR than authorised medicines [relative risk (RR) 1.67, 95% CI 1.38 to 2.02; p  48 hours, the overall incidence of definite and probable ADRs based on all admissions was 15.9% (95% CI 15.0 to 16.8). Opiate analgesic drugs and drugs used in general anaesthesia (GA) accounted for > 50% of all drugs implicated in ADRs. The odds ratio of an OLUL drug being implicated in an ADR compared with an authorised drug was 2.25 (95% CI 1.95 to 2.59; p < 0.001). Risk factors identified were exposure to a GA, age, oncology treatment and number of medicines. The systematic review estimated that the incidence rates for ADRs causing hospital admission ranged from 0.4% to 10.3% of all children [pooled estimate of 2.9% (95% CI 2.6% to 3.1%)] and from 0.6% to 16.8% of all children exposed to a drug during hospital stay. New tools to assess causality and avoidability of ADRs have been developed and validated. Many parents described being dissatisfied with clinician communication about ADRs, whereas parents of children with cancer emphasised confidence in clinician management of ADRs and the way clinicians communicated about medicines. The accounts of children and young people largely reflected parents’ accounts. Clinicians described using all of the features of communication that parents wanted to see, but made active decisions about when and what to communicate to families about suspected ADRs, which meant that communication may not always match families’ needs and expectations. We developed a leaflet to assist clinicians in communicating ADRs to parents. Conclusion The Adverse Drug Reactions In Children (ADRIC) programme has provided the most comprehensive assessment, to date, of the size and nature of ADRs in children presenting to, and cared for in, hospital, and the outputs that have resulted will improve the management and understanding of ADRs in children and adults within the NHS. Recommendations for future research: assess the values that parents and children place on the use of different medicines and the risks that they will find acceptable within these contexts; focusing on high-risk drugs identified in ADRIC, determine the optimum drug dose for children through the development of a gold standard practice for the extrapolation of adult drug doses, alongside targeted pharmacokinetic/pharmacodynamic studies; assess the research and clinical applications of the Liverpool Causality Assessment Tool and the Liverpool Avoidability Assessment Tool; evaluate, in more detail, morbidities associated with anaesthesia and surgery in children, including follow-up in the community and in the home setting and an assessment of the most appropriate treatment regimens to prevent pain, vomiting and other postoperative complications; further evaluate strategies for communication with families, children and young people about ADRs; and quantify ADRs in other settings, for example critical care and neonatology

Enhanced images and new models of the Wilkes Subglacial Basin help constrain the variability in geological boundary conditions for the East Antarctic Ice Sheet

The Wilkes Subglacial Basin (WSB) is a huge tectonic feature formed by Cenozoic lithospheric flexure coupled with Mesozoic to Cenozoic extension localised in sub-basins (Paxman et al., 2019, JGR). The deep northern WSB underlies the catchments of the Matusevich, Cook, Ninnis and Mertz glaciers that are largely marine-based, which renders them more vulnerable to past and predicted future ocean and climate warming. Here we present airborne radar and enhanced magnetic and gravity views of the northern WSB that help unveil the spatial variability in geological boundary conditions for this key sector of the East Antarctic Ice Sheet (EAIS). Residual gravity anomalies obtained by stripping out Moho effects were compared with aeromagnetic anomaly images to glean new perspectives into intra-crustal features. Depth to magnetic and gravity source estimates were then used to help derive the first combined 2D forward models for the region. We first examine a model crossing the northern WSB extending from the Matusevich Glacier to the deep Cook Basins. The model reveals a major crustal boundary along the eastern margin of the WSB interpreted as separating the Ross Orogen from a composite Precambrian Wilkes Terrane buried beneath Devonian to Jurassic sediments and early Cambrian metasediments. By analogy with the better understood Rennick Graben in northern Victoria Land, the Cook basins are interpreted as glacially over deepened grabens. The Cook basins clearly play a major role in EAIS dynamics, as they steer fast glacial flow deep into the interior of East Antarctica where they connect to the Central Basins. Our new model across these basins shows that the inferred Precambrian basement is both shallower and of more felsic bulk composition compared to the Cook basins. This fundamental difference in basement depth, bulk composition and thickness of sedimentary cover is likely to exert major influences on geothermal heat variability in this key sector of the EAIS

Demographic associations with stage of readiness to screen for colorectal cancer

Objective: To describe the distribution of a population in southern urban Adelaide in terms of readiness to screen for colorectal cancer (CRC) by Faecal Occult Blood Test (FOBT) or colonoscopy according to the stages in the Transtheoretical Model (TTM) of behaviour change and to compare the stages according to demographic variables. Methods: A random sample of 664 South Australians aged 50 to 74 were surveyed in June 2006. Chi-squared analyses were performed to determine if statistically significant differences on demographic variables existed between participants at different stages of readiness to screen

Patterns of participation over four rounds of annual fecal immunochemical test-based screening for colorectal cancer: what predicts rescreening?

Published online: 01 August 2017Background: Participation at the recommended intervals is critical for screening to be effective in reducing colorectal cancer (CRC) incidence. This study describes patterns of screening participation over four rounds of fecal immunochemical testing (FIT) to identify whether demographic variables and prior screening satisfaction are significantly associated with patterns of re-participation. Methods: Baseline surveys were mailed to 4000 South Australians randomly selected from the electoral-roll. Respondents (n = 1928/48.2%) were offered four annual FIT rounds. Screening participation and satisfaction at each round were recorded. Results: Study participation was 58.5, 66.9, 73.1 and 71.4% respectively over four rounds. Three participation patterns were described: consistent participation (43.1%), consistent non-participation (26.4%) and inconsistent participation (changeable; 30.5%), including intermittent and sustained change patterns. Sustained change described those who changed participatory behavior and then maintained for at least two rounds (n = 375/19.5%). Older people, and those not working were most likely to sustain participation. Younger invitees, especially men, were more likely to change participatory behavior and sustain the change. People with higher disadvantage, less education, not working and with no prior (pre-trial) screening experience were more likely to start participating and drop out. People dissatisfied with a prior screening test, including finding aspects embarrassing or unpleasant, were also more likely not to participate in annual screening or to drop out. Conclusions: The findings identify those at risk of non- or inconsistent participation in rescreening. They should aid targeting of interventions for demographic groups at risk and ensuring screening experiences are not perceived as unpleasant or difficult.Joanne M. Osborne, Carlene Wilson, Amy Duncan, Stephen R. Cole, Ingrid Flight, Deborah Turnbull, Donna L. Hughes and Graeme P. Youn