Challenges developing evidence-based algorithms for the trauma reception and resuscitation project

A project based at the Alfred Emergency and Trauma Centre in Melbourne, Australia aimed to standardise trauma resuscitation, documentation and interventions by developing best practice algorithms. The primary study objective was to demonstrate a reduction in management errors using a real-time computer based algorithm (the study group) compared to the control group in an open randomised controlled interventional study. A baseline control group was also used for comparison with usual (current) practice. In order to examine the existing evidence and algorithms in trauma care, nine teams of emergency nurses and doctors were formed. Specific literature searches performed by each team revealed a paucity of evidence supporting clinical practice in the trauma setting for procedures. Subsequently, the multidisciplinary teams worked together and developed algorithms based on best practice. The process revealed three main areas of challenges in the development of algorithms: (i) clinical, (ii) research and (iii) nursing challenges. The completion of the project demonstrated benefits in the real-time computer based algorithm with a reduction in the error rate per patient from the baseline control group to the intervention study group (2.30 vs. 2.13, p = 0.04) and error-free resuscitations increasing from 16% to 21.8% (p = .049). This project supported the implementation of a real-time computer based algorithm system with improved protocol compliance and reduced errors and morbidity.     

Pharmacodynamics and subchronic toxicity in mice and monkeys of ISIS 388626, a second-generation antisense oligonucleotide that targets human sodium glucose cotransporter 2

ISIS 388626, a 2'-methoxyethyl (MOE)-modified antisense oligonucleotide (ASO) that targets human sodium glucose cotransporter 2 (SGLT2) mRNA, is in clinical trials for the management of diabetes. SGLT2 plays a pivotal role in renal glucose reabsorption, and inhibition of SGLT2 is anticipated to reduce hyperglycemia in diabetic subjects by increasing urinary glucose elimination. To selectively inhibit SGLT2 in the kidney, ISIS 388626 was designed as a "shortmer" ASO, consisting of only 12 nucleotides with two 2'-MOE-modified nucleotides at the termini. Mice and monkeys received up to 30 mg/kg/week ISIS 388626 via subcutaneous injection for 6 or 13 weeks. Dose-dependent decreases in renal SGLT2 mRNA expression were observed, which correlated with dose-related increases in glucosuria without concomitant hypoglycemia. There were no histologic changes in the kidney attributed to SGLT2 inhibition after 6 or 13 weeks of treatment. The remaining changes observed in these studies were typical of those produced in these species by the administration of oligonucleotides, correlated with high doses of ISIS 388626, and were unrelated to the inhibition of SGLT2 expression. The kidney contained the highest concentration of ISIS 388626, and dose-dependent basophilic granule accumulation in tubular epithelial cells of the kidney, which is evidence of oligonucleotide accumulation in these cells, was the only histologic change identified. No changes in kidney function were observed. These results revealed only readily reversible changes after the administration of ISIS 388626 and support the continued investigation of the safety and efficacy of ISIS 388626 in human trials.     

Human factors and online learning

A human factors approach to patient safety offers a means of minimising the incidence and effect of adverse events in the healthcare setting. This article explains how human factors informed the development of an online patient safety course by the Royal College of Nursing. It also describes a novel educational technique called action mapping, which was used to design the online learning course.     

Virtual reality games for rehabilitation of people with stroke: perspectives from the users

PURPOSE. The purpose of this study is to evaluate the feasibility and users' perspectives of a novel virtual reality (VR) game-based rehabilitation intervention for people with stroke. METHOD. Six people with upper limb hemiplegia participated in a 6-week intervention that involved VR games. A series of eight progressively complex games was developed that required participants to navigate a submarine in a virtual ocean environment. Movement of the submarine was directed by forces applied to an arm interface by the affected limb. Outcome measures included assessments of arm function, questionnaires evaluating the intervention and a semi-structured interview concerning the participants' opinion of the intervention. RESULTS. All participants improved their performance on the games, although there were limited changes in clinical measures of arm function. All participants reported that they enjoyed the intervention with a wide range of overall perceptions of the experience of using VR. Three themes emerging from the interview data were: stretching myself, purpose and expectations of the intervention and future improvements. CONCLUSIONS. Participants found that taking part in this pilot study was enjoyable and challenging. Participants' feedback suggested that the games may be motivating and engaging for future users and have provided a basis for further development of the intervention.     

Badger responses to small-scale culling may compromise targeted control of bovine tuberculosis

Where wildlife disease requires management, culling is frequently considered but not always effective. In the British Isles, control of cattle tuberculosis (TB) is hindered by infection in wild badger (Meles meles) populations. Large-scale badger culling can reduce the incidence of confirmed cattle TB, but these benefits are undermined by culling-induced changes in badger behavior (termed perturbation), which can increase transmission among badgers and from badgers to cattle. Test–vaccinate/remove (TVR) is a novel approach that entails testing individual badgers for infection, vaccinating test-negative animals, and killing test-positive animals. Imperfect capture success, diagnostic sensitivity, and vaccine effectiveness mean that TVR would be expected to leave some infected and some susceptible badgers in the population. Existing simulation models predict that TVR could reduce cattle TB if such small-scale culling causes no perturbation, but could increase cattle TB if considerable perturbation occurs. Using data from a long-term study, we show that past small-scale culling was significantly associated with four metrics of perturbation in badgers: expanded ranging, more frequent immigration, lower genetic relatedness, and elevated prevalence of Mycobacterium bovis, the causative agent of TB. Though we could not reject the hypothesis that culling up to three badgers per social group might avoid perturbation, we also could not reject the hypothesis that killing a single badger prompted detectable perturbation. When considered alongside existing model predictions, our findings suggest that implementation of TVR, scheduled for 2014, risks exacerbating the TB problem rather than controlling it. Ongoing illegal badger culling is likewise expected to increase cattle TB risks.Infectious diseases are often difficult to control where wildlife hosts contribute to pathogen persistence. Wildlife culling is a frequently considered control option, which is sometimes effective (1, 2), but often ineffective (3–6).In the United Kingdom, the cattle farming industry is seriously affected by bovine tuberculosis (TB) caused by Mycobacterium bovis (7). Selective culling of test-positive cattle has helped to eradicate TB across much of the developed world, but eradication from the United Kingdom is impeded by M. bovis infection in European badgers (Meles meles) (8), as well as by continued transmission among cattle (9–11). Transmission has also been documented among badgers (12), from cattle to badgers (13), and from badgers to cattle (14, 15). Because badgers are clearly a contributing factor to the UK’s TB problem, successive TB control policies have included culling of badgers (7, 8). To date, cattle controls have emphasized selective slaughter of test-positive animals, whereas badger culls have typically been nonselective, with no testing of live animals before culling (but see ref. 16).The impacts of nonselective badger culling on M. bovis transmission are well established. Such culling reduces badger density (17), but also promotes dispersal into the culled area (18) as well as expanding badger ranging in and around the areas where culls occurred (19). In Britain these behavioral changes—termed social perturbation—have been linked to increases in the proportion of badgers infected with M. bovis (13, 20), and reductions in the spatial clustering of infection (21). In cattle, the incidence of confirmed TB was reduced inside large culling areas where badger numbers were substantially suppressed by annual “proactive” culling. However, on adjoining unculled lands, and in areas receiving localized “reactive” culling, reductions in badger numbers were smaller, the incidence of confirmed cattle TB was elevated (14, 15, 22–24), and spatial clustering of cattle infection was reduced (21).This propensity of nonselective badger culling to prompt social perturbation and hence increase disease transmission is a major constraint on its utility as a tool for controlling cattle TB. An alternative approach, first proposed in the 1980s, would be to target culling at test-positive badgers, just as current controls target test-positive cattle (16, 25). A further elaboration, termed test–vaccinate/remove (TVR), involves killing test-positive badgers while vaccinating test-negative badgers. A pilot TVR program is scheduled to take place across 100 sq km in Northern Ireland in 2014 (26).Selective culling approaches (such as TVR) are likely to remove relatively small numbers of badgers. First, constraints on capture success limit testing to 56–85% of the badger population (27, 28). Second, not all captured badgers will be infected with M. bovis: in the 10 initial proactive culls of the Randomized Badger Culling Trial (RBCT), 2–38% of badgers had infection detectable by bacterial culture at standard necropsy (29). Third, not all infected badgers are detectable by available live tests: the only available trap-side test detected 49% of badgers that were culture-positive at necropsy (30), and standard necropsy itself detected only 55% of infected badgers (31). This combination of imperfect capture success, low average infection prevalence, and imperfect test sensitivity means that the numbers of badgers to be killed by selective culling would probably be low, usually just one or two badgers within a social group (32). The same factors, combined with incomplete vaccine efficacy (33), mean that some infected and some susceptible badgers would be expected to remain despite implementation of TVR.Simulations indicate that the likely consequences of TVR for cattle TB control are highly sensitive to assumptions about whether culling small numbers of badgers prompts social perturbation (34, 35). Neither cage trapping for testing nor vaccination has been found to cause behavioral change. If the culling component of TVR likewise causes no perturbation, then TVR is predicted to reduce the prevalence of M. bovis infection in badgers and hence the incidence of cattle TB (34, 35). However, if TVR causes perturbation similar to that associated with past large- and small-scale culling, then it is projected to prompt sustained (34) or transient (35) increases in cattle TB. Unfortunately, it is not known which of these scenarios is more likely. Although the behavioral and epidemiological consequences of nonselective culling are relatively well understood, there have been no empirical studies of badgers’ behavioral responses to killing small numbers of animals per social group, as would occur under TVR and other forms of selective culling.In this paper, we use data from a large-scale study to assess whether killing small numbers of badgers would be expected to prompt social perturbation. We compare patterns of badger movement and M. bovis infection at the start of the RBCT (conducted 1998–2005) (14) with two indices of badger mortality. Our first measure, road density, provides an index of the numbers of badgers killed in road accidents (36), an important cause of badger mortality in Britain (37, 38). Our second measure is prior nonselective culling, conducted during the period 1986–1998 as small-scale badger removal operations (BROs), which typically targeted single farms (8). We hypothesized that high road densities and intense prior culling would each lead to expanded badger movement and elevated M. bovis prevalence. Further, we hypothesized that perturbation might be avoided if the number of badgers killed remained below a certain threshold, and sought to estimate this threshold.