Building a house on shifting sand: methodological considerations when evaluating the implementation and adoption of national electronic health record systems

Background: A commitment to Electronic Health Record (EHR) systems now constitutes a core part of many governments’ healthcare reform strategies. The resulting politically-initiated large-scale or national EHR endeavors are challenging because of their ambitious agendas of change, the scale of resources needed to make them work, the (relatively) short timescales set, and the large number of stakeholders involved, all of whom pursue somewhat different interests. These initiatives need to be evaluated to establish if they improve care and represent value for money. Methods: Critical reflections on these complexities in the light of experience of undertaking the first national, longitudinal, and sociotechnical evaluation of the implementation and adoption of England’s National Health Service’s Care Records Service (NHS CRS). Results/discussion: We advance two key arguments. First, national programs for EHR implementations are likely to take place in the shifting sands of evolving sociopolitical and sociotechnical and contexts, which are likely to shape them in significant ways. This poses challenges to conventional evaluation approaches which draw on a model of baseline operations → intervention → changed operations (outcome). Second, evaluation of such programs must account for this changing context by adapting to it. This requires careful and creative choice of ontological, epistemological and methodological assumptions. Summary: New and significant challenges are faced in evaluating national EHR implementation endeavors. Based on experiences from this national evaluation of the implementation and adoption of the NHS CRS in England, we argue for an approach to these evaluations which moves away from seeing EHR systems as Information and Communication Technologies (ICT) projects requiring an essentially outcome-centred assessment towards a more interpretive approach that reflects the situated and evolving nature of EHR seen within multiple specific settings and reflecting a constantly changing milieu of policies, strategies and software, with constant interactions across such boundaries

A pragmatic harm reduction approach to manage a large outbreak of wound botulism in people who inject drugs, Scotland 2015

Abstract Background People who inject drugs (PWID) are at an increased risk of wound botulism, a potentially fatal acute paralytic illness. During the first 6 months of 2015, a large outbreak of wound botulism was confirmed among PWID in Scotland, which resulted in the largest outbreak in Europe to date. Methods A multidisciplinary Incident Management Team (IMT) was convened to conduct an outbreak investigation, which consisted of enhanced surveillance of cases in order to characterise risk factors and identify potential sources of infection. Results Between the 24th of December 2014 and the 30th of May 2015, a total of 40 cases were reported across six regions in Scotland. The majority of the cases were male, over 30 and residents in Glasgow. All epidemiological evidence suggested a contaminated batch of heroin or cutting agent as the source of the outbreak. There are significant challenges associated with managing an outbreak among PWID, given their vulnerability and complex addiction needs. Thus, a pragmatic harm reduction approach was adopted which focused on reducing the risk of infection for those who continued to inject and limited consequences for those who got infected. Conclusions The management of this outbreak highlighted the importance and need for pragmatic harm reduction interventions which support the addiction needs of PWID during an outbreak of spore-forming bacteria. Given the scale of this outbreak, the experimental learning gained during this and similar outbreaks involving spore-forming bacteria in the UK was collated into national guidance to improve the management and investigation of future outbreaks among PWID

Education and employment outcomes of young adults with a history of developmental language disorder

Background: Developmental language disorder (DLD) presents a considerable barrier for young adults to engage in further education and training. Early studies with young adults with DLD revealed poor educational achievement and lack of opportunities to progress in education. More recent studies have provided more positive findings. Relatively sparse data exist, however, on current cohorts and the factors that predict outcomes. Aims: To examine educational and employment outcomes in young adulthood in a sample of people with histories of DLD, compared with an age-matched peer group without DLD. We ask: How do educational pathways and early jobs compare between those with and without DLD? Are young adults with DLD receiving similar levels of income as their peers? To what extent are language and literacy abilities associated with outcomes? Methods & Procedures: Participants included 84 individuals with DLD (67% males) and 88 age-matched peers without DLD (56% males). Participants were on average 24 years of age. They completed a battery of psycholinguistic, literacy and nonverbal skills assessments. Data were also collected on educational qualifications, current educational status, extent of educational support received, employment status, history and support, as well as current income. Outcomes & Results: Those with DLD obtained lower academic and vocational qualifications. Higher educational/vocational qualifications were associated with better language, better reading and higher PIQ. There were few differences between the two groups in terms of engagement with education but the mean age at leaving education was significantly earlier in the participants with DLD. Substantially more participants with DLD reported receiving support or dispensation from their educational institution. There was no significant difference between groups in the proportion of young people currently employed, though a higher proportion of the age-matched peers was in work full-time. Participants with DLD were much more likely to be in non-professional occupations. However, when examining pay in relation to types of occupation, the groups’ incomes were broadly comparable. Conclusions & Implications: At the group level, young people with a history of DLD more commonly have less skilled employment and more rarely achieve professional roles. At the individual level, there is considerable variation with smaller but not trivial proportions of young adults with a history of DLD showing good educational and employment outcomes. There are positive aspects to early adult outcomes for some young people with a history of DLD

RNA-seq Analysis Reveals That an ECF σ Factor, AcsS, Regulates Achromobactin Biosynthesis in Pseudomonas syringae pv. syringae B728a

Iron is an essential micronutrient for Pseudomonas syringae pv. syringae strain B728a and many other microorganisms; therefore, B728a has evolved methods of iron acquirement including the use of iron-chelating siderophores. In this study an extracytoplasmic function (ECF) sigma factor, AcsS, encoded within the achromobactin gene cluster is shown to be a major regulator of genes involved in the biosynthesis and secretion of this siderophore. However, production of achromobactin was not completely abrogated in the deletion mutant, implying that other regulators may be involved such as PvdS, the sigma factor that regulates pyoverdine biosynthesis. RNA-seq analysis identified 287 genes that are differentially expressed between the AcsS deletion mutant and the wild type strain. These genes are involved in iron response, secretion, extracellular polysaccharide production, and cell motility. Thus, the transcriptome analysis supports a role for AcsS in the regulation of achromobactin production and the potential activity of both AcsS and achromobactin in the plant-associated lifestyle of strain B728a

Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis

Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1 alpha and IL-1 beta); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p=9.3 x 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1,7%; p=3.5 x 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD (-0.04 to -0.02; -3.4%; p=7.7 x 10(-14)). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1.15 (1.08-1.22; p=1.8 x 10(-6)) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1.03 (1.02-1.04; p=3.9 x 10(-10)). Perallele odds ratios were 0.97 (0.95-0.99; p=9.9 x 10(-4)) for rheumatoid arthritis, 0.99 (0.97-1.01; p=0.47) for type 2 diabetes, 1.00 (0.98-1.02; p=0.92) for ischaemic stroke, and 1.08 (1.04-1.12; p=1.8 x 10(-5)) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1 alpha/beta inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Copyright (C) The Interleukin 1 Genetics Consortium. Open Access article distributed under the terms of CC-BY-NC-ND

Multidisciplinary investigations of the diets of two post-medieval populations from London using stable isotopes and microdebris analysis

This paper presents the first multi-tissue study of diet in post-medieval London using both the stable light isotope analysis of carbon and nitrogen and analysis of microdebris in dental calculus. Dietary intake was explored over short and long timescales. Bulk bone collagen was analysed from humans from the Queen’s Chapel of the Savoy (QCS) (n = 66) and the St Barnabas/St Mary Abbots (SB) (n = 25). Incremental dentine analysis was performed on the second molar of individual QCS1123 to explore childhood dietary intake. Bulk hair samples (n = 4) were sampled from adults from QCS, and dental calculus was analysed from four other individuals using microscopy. In addition, bone collagen from a total of 46 animals from QCS (n = 11) and the additional site of Prescot Street (n = 35) was analysed, providing the first animal dietary baseline for post-medieval London. Overall, isotopic results suggest a largely C3-based terrestrial diet for both populations, with the exception of QCS1123 who exhibited values consistent with the consumption of C4 food sources throughout childhood and adulthood. The differences exhibited in δ15Ncoll across both populations likely reflect variations in diet due to social class and occupation, with individuals from SB likely representing wealthier individuals consuming larger quantities of animal and marine fish protein. Microdebris analysis results were limited but indicate the consumption of domestic cereals. This paper demonstrates the utility of a multidisciplinary approach to investigate diet across long and short timescales to further our understanding of variations in social status and mobility

Trends in reported flooding in the UK: 1884–2013

A long term dataset of reported flooding based on reports from the UK Meteorological Office and the UK Centre for Ecology and Hydrology is described. This is possibly a unique dataset as the authors are unaware of any other 100+ year records of flood events and their consequences on a national scale. Flood events are classified by severity based upon qualitative descriptions. There is an increase in the number of reported flood events over time associated with an increased exposure to flooding as floodplain areas were developed. The data was de-trended for exposure, using population and dwelling house data. The adjusted record shows no trend in reported flooding over time, but there is significant decade to decade variability. This study opens a new approach considering flood occurrence over a long timescale using reported information (and thus likely effects on society) rather than just considering trends in extreme hydrological conditions.<br/