Electronic health records in ambulances: the ERA multiple-methods study

Background: Ambulance services have a vital role in the shift towards the delivery of health care outside hospitals, when this is better for patients, by offering alternatives to transfer to the emergency department. The introduction of information technology in ambulance services to electronically capture, interpret, store and transfer patient data can support out-of-hospital care. Objective: We aimed to understand how electronic health records can be most effectively implemented in a pre-hospital context in order to support a safe and effective shift from acute to community-based care, and how their potential benefits can be maximised. Design and setting: We carried out a study using multiple methods and with four work packages: (1) a rapid literature review; (2) a telephone survey of all 13 freestanding UK ambulance services; (3) detailed case studies examining electronic health record use through qualitative methods and analysis of routine data in four selected sites consisting of UK ambulance services and their associated health economies; and (4) a knowledge-sharing workshop. Results: We found limited literature on electronic health records. Only half of the UK ambulance services had electronic health records in use at the time of data collection, with considerable variation in hardware and software and some reversion to use of paper records as services transitioned between systems. The case studies found that the ambulance services’ electronic health records were in a state of change. Not all patient contacts resulted in the generation of electronic health records. Ambulance clinicians were dealing with partial or unclear information, which may not fit comfortably with the electronic health records. Ambulance clinicians continued to use indirect data input approaches (such as first writing on a glove) even when using electronic health records. The primary function of electronic health records in all services seemed to be as a store for patient data. There was, as yet, limited evidence of electronic health records’ full potential being realised to transfer information, support decision-making or change patient care. Limitations: Limitations included the difficulty of obtaining sets of matching routine data for analysis, difficulties of attributing any change in practice to electronic health records within a complex system and the rapidly changing environment, which means that some of our observations may no longer reflect reality. Conclusions: Realising all the benefits of electronic health records requires engagement with other parts of the local health economy and dealing with variations between providers and the challenges of interoperability. Clinicians and data managers, and those working in different parts of the health economy, are likely to want very different things from a data set and need to be presented with only the information that they need

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

What happens as student teachers who made very good use of ICT during pre‐service training enter their first year of teaching?

This paper looks at new teachers' use of information and communications technology (ICT) at the start of their first year of teaching. A previous study was made of 40 student teachers (May–July 2007) who were identified as very good users of ICT. This is a follow‐up study involving 30 of these 40 participants during their first months of teaching (November–February 2008). Drawing on interview and observation data the study describes the use these new teachers make of ICT and considers the factors which encourage and discourage that use. It finds that they continue to see ICT as supporting both their whole‐class teaching and pupils' independent working. The impact ICT has in the classroom provides the underlying rationale for its use by new teachers. Environmental factors, including access and expectations in school, further influence ICT use. Pre‐service training remains a strong influence, in particular past modelling of ICT use by mentors and tutors. The findings are discussed in the context of the wider literature

Why do some student teachers make very good use of ICT? An exploratory case study

This paper reports the findings from a study of student teachers at a university–school initial teacher education partnership in England. Forty student teachers, on primary and secondary teacher education programmes, were identified through tutor and mentor reports as making very good use of information and communication technologies (ICT). These student teachers were interviewed, and in many cases observed, teaching a lesson using ICT. Interviews covered their use of ICT in a particular lesson; their past experience of using ICT; factors encouraging or discouraging their use of ICT in school; and their beliefs about teaching and learning. Observations recorded their uses of hardware and software. Findings indicate that access, support for, and modelling of, ICT use in the classroom were key issues in developing this very good use of ICT. Equally important, however, seemed to be the belief that ICT could make a positive difference to teaching and learning and a willingness to ‘learn by doing’. These findings are reported in the context of the wider literature

Shared decision making in pregnancy in inflammatory bowel disease: design of a patient orientated decision aid

Background Research has indicated a lack of disease-specific reproductive knowledge among patients with Inflammatory Bowel Disease (IBD) and this has been associated with increased “voluntary childlessness”. Furthermore, a lack of knowledge may contribute to inappropriate medication changes during or after pregnancy. Decision aids have been shown to support decision making in pregnancy as well as in multiple other chronic diseases. A published decision aid for pregnancy in IBD has not been identified, despite the benefit of pre-conception counselling and patient desire for a decision support tool. This study aimed to develop and test the feasibility of a decision aid encompassing reproductive decisions in the setting of IBD. Methods The International Patient Decision Aid Standards were implemented in the development of the Pregnancy in IBD Decision Aid (PIDA). A multi-disciplinary steering committee was formed. Patient and clinician focus groups were conducted to explore themes of importance in the reproductive decision-making processes in IBD. A PIDA prototype was designed; patient interviews were conducted to obtain further insight into patient perspectives and to test the prototype for feasibility. Results Issues considered of importance to patients and clinicians encountering decisions regarding pregnancy in the setting of IBD included fertility, conception timing, inheritance, medications, infant health, impact of surgery, contraception, nutrition and breastfeeding. Emphasis was placed on the provision of preconception counselling early in the disease course. Decisions relating to conception and medications were chosen as the current focus of PIDA, however content inclusion was broad to support use across preconception, pregnancy and post-partum phases. Favourable and constructive user feedback was received. Conclusions The novel development of a decision aid for use in pregnancy and IBD was supported by initial user testing.Pharmaceutical Sciences, Faculty ofOther UBCNon UBCReviewedFacultyResearche

Cell-free hemoglobin is associated with increased vascular resistance and reduced peripheral perfusion in severe malaria

In severe falciparum malaria, unlike sepsis, hypotension on admission is uncommon. We hypothesized that low nitric oxide bioavailability due to the presence of cell-free hemoglobin (CFH) increases vascular tone in severe malaria.Published version. This work was supported by the Australian National Health and Medical Research Council (grants 605807, 496600, and 1037304 and fellowships 1042072 [to N. M. A.] and 605831 [to T. W. Y.]); the Australian government (UPRS and PIRTS scholarship to H. W. K.); University College, Oxford (Radcliffe Travelling Fellowship to MTH); and the Wellcome Trust, as part of the Wellcome Thailand Trust Major Oversees Programme fundin

In vivo modulation of extracellular hippocampal glutamate and GABA levels and limbic seizures by group I and II metabotropic glutamate receptor ligands

The effects of several metabotropic receptor (mGluR) ligands on baseline hippocampal glutamate and GABA overflow in conscious rats and the modulation of limbic seizure activity by these ligands were investigated. Intrahippocampal mGluR group I agonist perfusion via a microdialysis probe [1 mM (R,S)-3,5-dihydroxyphenylglycine] induced seizures and concomitant augmentations in amino acid dialysate levels. The mGlu(1a) receptor antagonist LY367385 (1 mM) decreased baseline glutamate but not GABA concentrations, suggesting that mGlu(1a) receptors, which regulate hippocampal glutamate levels, are tonically activated by endogenous glutamate. This decrease in glutamate may contribute to the reported LY367385-mediated anticonvulsant effect. The mGlu(5) receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine (50 mg/kg) also clearly abolished pilocarpine-induced seizures. Agonist-mediated actions at mGlu(2/3) receptors by LY379268 (100 muM, 10 mg/kg intraperitoneally) decreased basal hippocampal GABA but not glutamate levels. This may partly explain the increased excitation following systemic LY379268 administration and the lack of complete anticonvulsant protection within our epilepsy model with the mGlu(2/3) receptor agonist. Group II selective mGluR receptor blockade with LY341495 (1-10 muM) did not alter the rats' behaviour or hippocampal amino acid levels. These data provide a neurochemical basis for the full anticonvulsant effects of mGlu(1a) and mGlu(5) antagonists and the partial effects observed with mGlu(2/3) agonists in vivo

Whole-genome sequencing of patients with rare diseases in a national health system

Most patients with rare diseases do not receive a molecular diagnosis and the aetiological variants and causative genes for more than half such disorders remain to be discovered1. Here we used whole-genome sequencing (WGS) in a national health system to streamline diagnosis and to discover unknown aetiological variants in the coding and non-coding regions of the genome. We generated WGS data for 13,037 participants, of whom 9,802 had a rare disease, and provided a genetic diagnosis to 1,138 of the 7,065 extensively phenotyped participants. We identified 95 Mendelian associations between genes and rare diseases, of which 11 have been discovered since 2015 and at least 79 are confirmed to be aetiological. By generating WGS data of UK Biobank participants2, we found that rare alleles can explain the presence of some individuals in the tails of a quantitative trait for red blood cells. Finally, we identified four novel non-coding variants that cause disease through the disruption of transcription of ARPC1B, GATA1, LRBA and MPL. Our study demonstrates a synergy by using WGS for diagnosis and aetiological discovery in routine healthcare

Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis.

BACKGROUND: Rare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes. METHODS: We did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11 744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses. FINDINGS: A locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55-2·08], p=5·13 × 10-15) and a second locus in HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 [1·42-1·71], p=7·65 × 10-20) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25-1·48], p=1·69 × 10-12; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-mediated inhibition of the enhancer reduced SOX17 expression. The HLA-DPA1/DPB1 rs2856830 genotype was strongly associated with survival. Median survival from diagnosis in patients with pulmonary arterial hypertension with the C/C homozygous genotype was double (13·50 years [95% CI 12·07 to >13·50]) that of those with the T/T genotype (6·97 years [6·02-8·05]), despite similar baseline disease severity. INTERPRETATION: This is the first study to report that common genetic variation at loci in an enhancer near SOX17 and in HLA-DPA1/DPB1 is associated with pulmonary arterial hypertension. Impairment of SOX17 function might be more common in pulmonary arterial hypertension than suggested by rare mutations in SOX17. Further studies are needed to confirm the association between HLA typing or rs2856830 genotyping and survival, and to determine whether HLA typing or rs2856830 genotyping improves risk stratification in clinical practice or trials. FUNDING: UK NIHR, BHF, UK MRC, Dinosaur Trust, NIH/NHLBI, ERS, EMBO, Wellcome Trust, EU, AHA, ACClinPharm, Netherlands CVRI, Dutch Heart Foundation, Dutch Federation of UMC, Netherlands OHRD and RNAS, German DFG, German BMBF, APH Paris, INSERM, Université Paris-Sud, and French ANR