Realistic evaluation of EWS and ALERT: factors enabling and constraining implementation.

Realistic Evaluation of EWS and ALERT: factors enabling and constraining implementation Background The implementation of EWS and ALERT in practice is essential to the success of Rapid Response Systems but is dependent upon nurses utilising EWS protocols and applying ALERT best practice guidelines. To date there is limited evidence on the effectiveness of EWS or ALERT as research has primarily focused on measuring patient outcomes (cardiac arrests, ICU admissions) following the implementation of a Rapid Response Team. Complex interventions in healthcare aimed at changing service delivery and related behaviour of health professionals require a different research approach to evaluate the evidence. To understand how and why EWS and ALERT work, or might not work, research needs to consider the social, cultural and organisational influences that will impact on successful implementation in practice. This requires a research approach that considers both the processes and outcomes of complex interventions, such as EWS and ALERT, implemented in practice. Realistic Evaluation is such an approach and was used to explain the factors that enable and constrain the implementation of EWS and ALERT in practice [1]. Aim The aim of this study was to evaluate factors that enabled and constrained the implementation and service delivery of early warnings systems (EWS) and ALERT in practice in order to provide direction for enabling their success and sustainability. Methods The research design was a multiple case study approach of four wards in two hospitals in Northern Ireland. It followed the principles of realist evaluation research which allowed empirical data to be gathered to test and refine RRS programme theory. This approach used a variety of mixed methods to test the programme theories including individual and focus group interviews, observation and documentary analysis in a two stage process. A purposive sample of 75 key informants participated in individual and focus group interviews. Observation and documentary analysis of EWS compliance data and ALERT training records provided further evidence to support or refute the interview findings. Data was analysed using NVIVO8 to categorise interview findings and SPSS for ALERT documentary data. These findings were further synthesised by undertaking a within and cross case comparison to explain the factors enabling and constraining EWS and ALERT. Results A cross case analysis highlighted similarities, differences and factors enabling or constraining successful implementation across the case study sites. Findings showed that personal (confidence; clinical judgement; personality), social (ward leadership; communication), organisational (workload and staffing issues; pressure from managers to complete EWS audit and targets), educational (constraints on training; no clinical educator on ward) and cultural (routine task delegated) influences impact on EWS and acute care training outcomes. There were also differences noted between medical and surgical wards across both case sites. Conclusions Realist Evaluation allows refinement and development of the RRS programme theory to explain the realities of practice. These refined RRS programme theories are capable of informing the planning of future service provision and provide direction for enabling their success and sustainability. References: 1. McGaughey J, Blackwood B, O’Halloran P, Trinder T. J. & Porter S. (2010) A realistic evaluation of Track and Trigger systems and acute care training for early recognition and management of deteriorating ward–based patients. Journal of Advanced Nursing 66 (4), 923-932. Type of submission: Concurrent session Source of funding: Sandra Ryan Fellowship funded by the School of Nursing & Midwifery, Queen’s University of Belfast

Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 × 10(-5), Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10(-06)/Pfemales: 3.45 × 10(-07)/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the association with obesity was primarily driven by females. In addition, the detected altered hypothalamic expression patterns of Ctbp2 and Nbeal1 as a result of fasting and DIO implicate these genes in weight regulation.

The influence of market deregulation on fast food consumption and body mass index:A cross-national time series analysis

Objective
To investigate the effect of fast food consumption on mean population body mass index (BMI) and explore the possible influence of market deregulation on fast food consumption and BMI.

Methods
The within-country association between fast food consumption and BMI in 25 high-income member countries of the Organisation for Economic Co-operation and Development between 1999 and 2008 was explored through multivariate panel regression models, after adjustment for per capita gross domestic product, urbanization, trade openness, lifestyle indicators and other covariates. The possible mediating effect of annual per capita intake of soft drinks, animal fats and total calories on the association between fast food consumption and BMI was also analysed. Two-stage least squares regression models were conducted, using economic freedom as an instrumental variable, to study the causal effect of fast food consumption on BMI.

Findings
After adjustment for covariates, each 1-unit increase in annual fast food transactions per capita was associated with an increase of 0.033 kg/m2 in age-standardized BMI (95% confidence interval, CI: 0.013–0.052). Only the intake of soft drinks – not animal fat or total calories – mediated the observed association (β: 0.030; 95% CI: 0.010–0.050). Economic freedom was an independent predictor of fast food consumption (β: 0.27; 95% CI: 0.16–0.37). When economic freedom was used as an instrumental variable, the association between fast food and BMI weakened but remained significant (β: 0.023; 95% CI: 0.001–0.045).

Conclusion
Fast food consumption is an independent predictor of mean BMI in high-income countries. Market deregulation policies may contribute to the obesity epidemic by facilitating the spread of fast food.

Cross-age tutoring in kindergarten and elementary school settings: a systmeatic review and meta-analysis

Background: Qualified teaching staffs are neither available nor affordable to provide large numbers of children with individual attention. One solution to providing individual tuition has been the development of tutoring programs that are delivered by nonprofessional tutors, such as classmates, older children and community volunteers. Objectives: We have conducted a systematic review of cross-age tutoring interventions delivered by non-professional tutors to children between 5 and 11 years old. Only randomized controlled trials with reliable measures of academic outcomes, and continuing for at least 12 weeks, compared to instruction as usual, were included. Results: Searches of electronic databases and previous reviews, and contacts with researchers yielded 11,564 titles; after screening, 15 studies were included in the analysis. Cross-age tutoring showed small significant effects for tutees on the composite measure of reading (g=0.18, 95% CI: 0.08, 0.27, N=8251), decoding skills (g=0.29, 95% CI: 0.13, 0.44, N=7081), and reading comprehension (g=0.11, 95% CI: 0.01, 0.21, N=6945). No significant effects were detected for other reading sub-skills or for mathematics. The quality of evidence is decreased by study limitations and high heterogeneity of effects. Conclusions: The benefits for tutees of non-professional peer and cross-age tutoring can be given a positive but weak recommendation, considering the low quality of evidence and lack of cost information. Subgroup analyses suggested that highly-structured reading programs may be more useful than loosely-structured programs. Large-scale replication trials using factorial design, process evaluations, reliable outcome measures and logic models are needed to better understand under what conditions, and for whom, cross-age non-professional tutoring may be effective.

Cross-age tutoring in kindergarten and elementary school settings: A systematic review and meta-analysis

This systematic review summarizes effects of peer tutoring delivered to children between 5 and 11 years old by non-professional tutors, such as classmates, older children and adult community peer volunteers. Inclusion criteria for the review included tutoring studies with a randomized controlled trial design, reliable measures of academic outcomes, and duration of at least 12 weeks. Searches of electronic databases, previous reviews, and contacts with researchers yielded 11,564 titles. After screening, 15 studies were included in the analysis. Cross-age tutoring showed small significant effects for tutees on the composite measure of reading (g = 0.18, 95% CI: 0.08, 0.27, N = 8251), decoding skills (g = 0.29, 95% CI: 0.13, 0.44, N = 7081), and reading comprehension (g = 0.11, 95% CI: 0.01, 0.21, N = 6945). No significant effects were detected for other reading sub-skills or for mathematics. The benefits to tutees of non-professional cross-age peer tutoring can be given a positive, but weak recommendation. Effect Sizes were modest and in the range −0.02 to 0.29. Questions regarding study limitations, lack of cost information, heterogeneity of effects, and the relatively small number of studies that have used a randomized controlled trial design means that the evidence base is not as strong as it could be. Subgroup analyses of included studies indicated that highly-structured reading programmes were of more benefit than those that were loosely-structured. Large-scale replication trials using factorial designs, reliable outcome measures, process evaluations and logic models are needed to better understand under what conditions, and for whom, cross-age non-professional peer tutoring may be most effective.

3D-QSAR studies on 4-Hydroxyphenylpyruvate Dioxygenase inhibitors by comparative molecular field analysis (CoMFA)

A comparative molecular field analysis (CoMFA) of alkanoic acid 3-oxo-cyclohex-1-enyl ester and 2-acylcyclohexane-1,3-dione derivatives of 4-hydroxyphenylpyruvate dioxygenase inhibitors has been performed to determine the factors required for the activity of these compounds. The substrate's conformation abstracted from dynamic modeling of the enzyme-substrate complex was used to build the initial structures of the inhibitors. Satisfactory results were obtained after an all-space searching procedure, performing a leave-one out (LOO) cross-validation study with cross-validation q(2) and conventional r(2) values of 0.779 and 0.989, respectively. The results provide the tools for predicting the affinity of related compounds, and for guiding the design and synthesis of new HPPD ligands with predetermined affinities.

Quaternary pollen analysis: recent progress in palaeoecology and palaeoclimatology

During the last decade Quaternary pollen analysis has developed towards improved pollen-taxonomical precision, automated pollen identification and more rigorous definition of pollen assemblage zones. There have been significant efforts to model the spatial representation of pollen records in lake sediments which is important for more precise interpretation of the pollen records in terms of past vegetation patterns. We review the difficulties in matching modelled post-glacial plant migration patterns with pollen-based palaeorecords and discuss the potential of DNA analysis of pollen to investigate the ancestry and past migration pathways of the plants. In population ecology there has been an acceleration of the widely advocated conceptual advance of pollen-analytical research from vaguely defined ‘environmental reconstructions’ towards investigating more precisely defined ecological problems aligned with the current ecological theories. Examples of such research have included an increasing number of investigations about the ecological impacts of past disturbances, often integrating pollen records with other palaeoecological data. Such an approach has also been applied to incorporate a time perspective to the questions of ecosystem restoration, nature conservation and forest management. New lines of research are the use of pollen analysis to study long-term patterns of vegetation diversity, such as the role of glacial-age vegetation fragmentation as a cause of Amazonian rain forest diversity, and to investigate links between pollen richness and past plant diversity. Palaeoclimatological use of pollen records has become more quantitative and has included more precise and rigorous testing of pollen-climate calibration models with modern climate data. These tests show the approximate nature of the models and warn against a too straightforward climatic interpretation of the small-scale variation in reconstructions. Pollenbased climate reconstructions over the Late Glacial–early Holocene boundary have indicated that pollen-stratigraphical changes have been rapid with no evidence for response lags. This does not rule out the possibility of migrational disequilibrium, however, as the rapid changes may be mostly due to nonmigrational responses of existing vegetation. It is therefore difficult to assess whether the amplitude of reconstructed climate change reflects real climate change. Other outstanding problems remain the obscure relationship of pollen production and climate, the role of human impact and other nonclimatic factors, and nonanalogue situations.

Flatworm nerve-muscle: structural and functional analysis

Platyhelminthes occupy a unique position in nerve-muscle evolution, being the most primitive of metazoan phyla. Essentially, their nervous system consists of an archaic brain and associated pairs of longitudinal nerve cords cross-linked as an orthogon by transverse commissures. Confocal imaging reveals that these central nervous system elements are in continuity with an array of peripheral nerve plexuses which innervate a well-differentiated grid work of somatic muscle as well as a complexity of myofibres associated with organs of attachment, feeding, and reproduction. Electrophysiological studies of flatworm muscles have exposed a diversity of voltage-activated ion channels that influence muscle contractile events. Neuronal cell types are mainly multi- and bi-polar and highly secretory in nature, producing a heterogeneity of vesicular inclusions whose contents have been identified cytochemically to include all three major types of cholinergic, aminergic, and peptidergic messenger molecules. A landmark discovery in flatworm neurobiology was the biochemical isolation and amino acid sequencing of two groups of native neuropeptides: neuropeptide F and FMRFamide-related peptides (FaRPs). Both families of neuropeptide are abundant and broadly distributed in platyhelminths, occurring in neuronal vesicles in representatives of all major flatworm taxa. Dual localization studies have revealed that peptidergic and cholinergic substances occupy neuronal sets separate from those of serotoninergic components. The physiological actions of neuronal messengers in flatworms are beginning to be established, and where examined, FaRPs and 5-HT are myoexcitatory, while cholinomimetic substances are generally inhibitory. There is immunocytochemical evidence that FaRPs and 5-HT have a regulatory role in the mechanism of egg assembly. Use of muscle strips and (or) muscle fibres from free-living and parasitic flatworms has provided baseline information to indicate that muscle responses to FaRPs are mediated by a G-protein-coupled receptor, and that the signal transduction pathway for contraction involves the second messengers cAMP and protein kinase C.

Psychological problems in children with cerebral palsy: A cross-sectional European study

Objectives: To describe psychological symptoms in 8–12-year-old children with cerebral palsy; to investigate predictors of these symptoms and their impact on the child and family.

Design: A cross-sectional multi-centre survey.

Participants: Eight hundred and eighteen children with cerebral palsy, aged 8–12 years, identified from population-based registers of cerebral palsy in eight European regions and from multiple sources in one further region.

Main outcome measures: The Strengths and Difficulties Questionnaire (SDQ)P4-16 and the Total Difficulties Score (TDS) dichotomised into normal/borderline (TDS = 16) versus abnormal (TDS > 16).

Statistical analysis: Multilevel, multivariable logistic regression to relate the presence of psychological symptoms to child and family characteristics.

Results: About a quarter of the children had TDS > 16 indicating significant psychological symptoms, most commonly in the domain Peer Problems. Better gross motor function, poorer intellect, more pain, having a disabled or ill sibling and living in a town were independently associated with TDS > 16. The risk of TDS > 16 was odds ratio (OR) = .2 (95% CI: .1 to .3) comparing children with the most and least severe functional limitations; OR = 3.2 (95%CI: 2.1 to 4.8) comparing children with IQ < 70 and others; OR = 2.7 (95% CI: 1.5 to 4.6) comparing children in severe pain and others; OR = 2.7 (95% CI:1.6 to 4.6) comparing children with another disabled sibling or OR = 1.8 (95%CI: 1.2 to 2.8) no siblings and others; OR = 1.8 (95% CI: 1.1 to 2.8) comparing children resident in a town and others. Among parents who reported their child to have psychological problems, 95% said they had lasted over a year, 37% said they distressed their child and 42% said they burdened the family at least ‘quite a lot’.

Conclusions: A significant proportion of children with cerebral palsy have psychological symptoms or social impairment sufficiently severe to warrant referral to specialist services. Care must be taken in the assessment and management of children with cerebral palsy to ensure psychological problems are not overlooked and potentially preventable risk factors like pain are treated effectively. The validity of the SDQ for children with severe disability warrants further assessment.

Confirmatory factor analysis of the adolescent self-report strengths and difficulties questionnaire

The Strengths and Difficulties Questionnaire (SDQ) is a widely used 25-item screening test for emotional and behavioral problems in children and adolescents. This study attempted to critically examine the factor structure of the adolescent self-report version. As part of an ongoing longitudinal cohort study, a total of 3,753 pupils completed the SDQ when aged 12. Both three- and five-factor exploratory factor analysis models were estimated. A number of deviations from the hypothesized SDQ structure were observed, including a lack of unidimensionality within particular subscales, cross-loadings, and items failing to load on any factor. Model fit of the confirmatory factor analysis model was modest, providing limited support for the hypothesized five-component structure. The analyses suggested a number of weaknesses within the component structure of the self-report SDQ, particularly in relation to the reverse-coded items.