Optimising use of electronic health records to describe the presentation of rheumatoid arthritis in primary care: a strategy for developing code lists

Background Research using electronic health records (EHRs) relies heavily on coded clinical data. Due to variation in coding practices, it can be difficult to aggregate the codes for a condition in order to define cases. This paper describes a methodology to develop ‘indicator markers’ found in patients with early rheumatoid arthritis (RA); these are a broader range of codes which may allow a probabilistic case definition to use in cases where no diagnostic code is yet recorded. Methods We examined EHRs of 5,843 patients in the General Practice Research Database, aged ≥30y, with a first coded diagnosis of RA between 2005 and 2008. Lists of indicator markers for RA were developed initially by panels of clinicians drawing up code-lists and then modified based on scrutiny of available data. The prevalence of indicator markers, and their temporal relationship to RA codes, was examined in patients from 3y before to 14d after recorded RA diagnosis. Findings Indicator markers were common throughout EHRs of RA patients, with 83.5% having 2 or more markers. 34% of patients received a disease-specific prescription before RA was coded; 42% had a referral to rheumatology, and 63% had a test for rheumatoid factor. 65% had at least one joint symptom or sign recorded and in 44% this was at least 6-months before recorded RA diagnosis. Conclusion Indicator markers of RA may be valuable for case definition in cases which do not yet have a diagnostic code. The clinical diagnosis of RA is likely to occur some months before it is coded, shown by markers frequently occurring ≥6 months before recorded diagnosis. It is difficult to differentiate delay in diagnosis from delay in recording. Information concealed in free text may be required for the accurate identification of patients and to assess the quality of care in general practice

Consenting to health record linkage: evidence from a multi-purpose longitudinal survey of a general population

Background: The British Household Panel Survey (BHPS) is the first long-running UK longitudinal survey with a non-medical focus and a sample covering the whole age range to have asked for permission to link to a range of administrative health records. This study determines whether informed consent led to selection bias and reflects on the value of the BHPS linked with health records for epidemiological research. Methods. Multivariate logistical regression is used, with whether the respondent gave consent to data linkage or not as the dependent variable. Independent variables were entered as four blocks; (i) a set of standard demographics likely to be found in most health registration data, (ii) a broader set of socio-economic characteristics, (iii) a set of indicators of health conditions and (iv) information about the use of health services. Results: Participants aged 16-24, males and those living in England were more likely to consent. Consent is not biased with respect to socio-economic characteristics or health. Recent users of GP services are underrepresented among consenters. Conclusions: Whilst data could only be linked for a minority of BHPS participants, the BHPS offers a great range of information on people's life histories, their attitudes and behaviours making it an invaluable source for epidemiological research. © 2012 Knies et al; licensee BioMed Central Ltd

Conformational transition of FGFR kinase activation revealed by site-­specific unnatural amino acid reporter and single molecule FRET

Protein kinases share significant structural similarity; however, structural features alone are insufficient to explain their diverse functions. Thus, bridging the gap between static structure and function requires a more detailed understanding of their dynamic properties. For example, kinase activation may occur via a switch-like mechanism or by shifting a dynamic equilibrium between inactive and active states. Here, we utilize a combination of FRET and molecular dynamics (MD) simulations to probe the activation mechanism of the kinase domain of Fibroblast Growth Factor Receptor (FGFR). Using genetically-encoded, site-specific incorporation of unnatural amino acids in regions essential for activation, followed by specific labeling with fluorescent moieties, we generated a novel class of FRET-based reporter to monitor conformational differences corresponding to states sampled by non phosphorylated/inactive and phosphorylated/active forms of the kinase. Single molecule FRET analysis in vitro, combined with MD simulations, shows that for FGFR kinase, there are populations of inactive and active states separated by a high free energy barrier resulting in switch-like activation. Compared to recent studies, these findings support diversity in features of kinases that impact on their activation mechanisms. The properties of these FRET-based constructs will also allow further studies of kinase dynamics as well as applications in vivo

Conformational transition of FGFR kinase activation revealed by site-specific unnatural amino acid reporter and single molecule FRET

Protein kinases share significant structural similarity; however, structural features alone are insufficient to explain their diverse functions. Thus, bridging the gap between static structure and function requires a more detailed understanding of their dynamic properties. For example, kinase activation may occur via a switch-like mechanism or by shifting a dynamic equilibrium between inactive and active states. Here, we utilize a combination of FRET and molecular dynamics (MD) simulations to probe the activation mechanism of the kinase domain of Fibroblast Growth Factor Receptor (FGFR). Using genetically-encoded, site-specific incorporation of unnatural amino acids in regions essential for activation, followed by specific labeling with fluorescent moieties, we generated a novel class of FRET-based reporter to monitor conformational differences corresponding to states sampled by non phosphorylated/inactive and phosphorylated/active forms of the kinase. Single molecule FRET analysis in vitro, combined with MD simulations, shows that for FGFR kinase, there are populations of inactive and active states separated by a high free energy barrier resulting in switch-like activation. Compared to recent studies, these findings support diversity in features of kinases that impact on their activation mechanisms. The properties of these FRET-based constructs will also allow further studies of kinase dynamics as well as applications in vivo

Analysis of dental care of children receiving comprehensive care under general anaesthesia at a teaching hospital in England

Objectives: This study aimed to analyse the characteristics of comprehensive dental care provided under general anaesthesia (CDGA) and to review the additional treatment required by children over the 6 years subsequent to CDGA. Method: Information collected from hospital records for the 6-year period following the first CDGA included the types of dental treatment performed at CDGA, the return rates for follow-up appointments, further treatment required subsequent to CDGA and the types of dental treatment performed at repeat DGA. Results: The study population consisted of 263 children, of whom 129 had a significant medical history, with mean age of 6.7 years. The results revealed that the waiting time for CDGA was significantly shorter in children who had a significant medical history, with 49 % being admitted for CDGA within 3 months of pre-GA assessment, as compared to 29 % of healthy children. 67 % of children had follow-up care recorded, with a slightly higher proportion of children with significant medical history returning for follow-up [70 % (90/129)] compared with 65 % (87/134) of healthy children. Re-treatment rates were 34 % (88/263), the majority of cases being treated under local analgesia (42/88). 34 of 263 children had repeat DGA (12.9 %). Of these 71 % (24/34) were children with significant medical history. The mean age at repeat DGA was 9 years. In 25 of 34 children (74 %), repeat DGA was due to trauma, oral pathology, supernumerary removal, hypomineralized teeth or new caries of previously sound or un-erupted teeth at CDGA. The ratio of extraction over restoration (excluding fissure sealants) performed at repeat DGA was 2.8, compared with the ratio of 1.3 in the initial CDGA. Conclusions: There was a higher ratio of extraction over restorations at the repeat DGA. This suggests that the prescribed treatments at repeat DGA were more aggressive as compared to the initial CDGA in 1997. The majority of the treatment required at repeat DGA was to treat new disease

Analysis of four studies in a comparative framework reveals: health linkage consent rates on British cohort studies higher than on UK household panel surveys

Background: A number of cohort studies and longitudinal household panel studies in Great Britain have asked for consent to link survey data to administrative health data. We explore commonalities and differences in the process of collecting consent, achieved consent rates and biases in consent with respect to socio-demographic, socio-economic and health characteristics. We hypothesise that British cohort studies which are rooted within the health sciences achieve higher consent rates than the UK household longitudinal studies which are rooted within the social sciences. By contrast, the lack of a specific health focus in household panel studies means there may be less selectivity in consent, in particular, with respect to health characteristics. Methods: Survey designs and protocols for collecting informed consent to health record linkage on two British cohort studies and two UK household panel studies are systematically compared. Multivariate statistical analysis is then performed on information from one cohort and two household panel studies that share a great deal of the data linkage protocol but vary according to study branding, survey design and study population. Results: We find that consent is higher in the British cohort studies than in the UK household panel studies, and is higher the more health-focused the study is. There are no systematic patterns of consent bias across the studies and where effects exist within a study or study type they tend to be small. Minority ethnic groups will be underrepresented in record linkage studies on the basis of all three studies. Conclusions: Systematic analysis of three studies in a comparative framework suggests that the factors associated with consent are idiosyncratic to the study. Analysis of linked health data is needed to establish whether selectivity in consent means the resulting research databases suffer from any biases that ought to be considered

A Novel Semi-Supervised Methodology for Extracting Tumor Type-Specific MRS Sources in Human Brain Data

BackgroundThe clinical investigation of human brain tumors often starts with a non-invasive imaging study, providing information about the tumor extent and location, but little insight into the biochemistry of the analyzed tissue. Magnetic Resonance Spectroscopy can complement imaging by supplying a metabolic fingerprint of the tissue. This study analyzes single-voxel magnetic resonance spectra, which represent signal information in the frequency domain. Given that a single voxel may contain a heterogeneous mix of tissues, signal source identification is a relevant challenge for the problem of tumor type classification from the spectroscopic signal.Methodology/Principal FindingsNon-negative matrix factorization techniques have recently shown their potential for the identification of meaningful sources from brain tissue spectroscopy data. In this study, we use a convex variant of these methods that is capable of handling negatively-valued data and generating sources that can be interpreted as tumor class prototypes. A novel approach to convex non-negative matrix factorization is proposed, in which prior knowledge about class information is utilized in model optimization. Class-specific information is integrated into this semi-supervised process by setting the metric of a latent variable space where the matrix factorization is carried out. The reported experimental study comprises 196 cases from different tumor types drawn from two international, multi-center databases. The results indicate that the proposed approach outperforms a purely unsupervised process by achieving near perfect correlation of the extracted sources with the mean spectra of the tumor types. It also improves tissue type classification.Conclusions/SignificanceWe show that source extraction by unsupervised matrix factorization benefits from the integration of the available class information, so operating in a semi-supervised learning manner, for discriminative source identification and brain tumor labeling from single-voxel spectroscopy data. We are confident that the proposed methodology has wider applicability for biomedical signal processing

Group-based memory rehabilitation for people with multiple sclerosis: subgroup analysis of the ReMiND trial

Background/Aim: Memory problems are frequently reported in people with multiple sclerosis (MS). These can be debilitating and affect individuals and their families. This sub-group analysis focused on the effectiveness of memory rehabilitation in patients with MS. Methods: Data were extracted from a single blind randomised controlled trial, the ReMiND trial, which also included participants with traumatic brain injury and stroke. Participants were randomly allocated to compensation or restitution treatment programmes, or a self-help control. The programmes were manual-based and comprised two individual and ten group sessions. Outcome measures included assessments of memory, mood and activities of daily living. A total of 39 patients with MS participated in this study (ten males (26%), 29 females (74%); mean±SD age: 48.3±10.8 years). Results: Comparison of groups showed no significant effect of treatment on memory, but there were significant differences between compensation and restitution on self-report symptoms of emotional distress at both 5- (p=0.04) and 7-month (p=0.05) follow-up sessions. The compensation group showed less distress than the restitution group. Conclusions: Individuals with MS who received compensation memory rehabilitation reported significantly less emotional distress than those who received restitution. Further research is needed to explore why self-reported memory problems did not differ between groups

Do Mismatches between Pre- and Post-Natal Environments Influence Adult Physiological Functioning?

Purpose: Mismatches between pre- and post-natal environments have implications for disease in adulthood. However, less is known about how this mismatch can affect physiological systems more generally, especially at younger ages. We hypothesised that mismatches between pre- and post-natal environments, as measured by the measures of birthweight and adult leg length, would be associated with poorer biomarker levels across five key physiological systems in young adults. Methods: Data were collected from 923, 36 year-old respondents from the West of Scotland Twenty-07 Study. The biomarkers were: systolic blood pressure (sBP); forced expiratory volume (FEV1); glycated haemoglobin (HbA1c); glomerular filtration rate (eGFR); and gamma- glutamyltransferase (GGT). These biomarkers were regressed against pre-natal conditions (birthweight), post-natal conditions (leg length) and the interaction between pre- and post-natal measures. Sex, childhood socioeconomic position and adult lifestyle characteristics were adjusted for as potential effect modifiers and confounders, respectively. Results: There were no associations between birthweight and leg length and sBP, FEV1, HbA1c, or GGT. Higher birthweight and longer leg length were associated with better kidney function (eGFR). However, there was no evidence for mismatches between birthweight and leg length to be associated with worse sBP, FEV1, HbA1c, eGFR or GGT levels (P>0.05). Conclusions: Our hypothesis that early signs of physiological damage would be present in young adults given mismatches in childhood environments, as measured by growth markers, was not proven. This lack of association could be because age 36 is too young to identify significant trends for future health, or the associations simply not being present. © 2014 Robertson, Benzeval

SPARC 2018 Internationalisation and collaboration : Salford postgraduate annual research conference book of abstracts

Welcome to the Book of Abstracts for the 2018 SPARC conference. This year we not only celebrate the work of our PGRs but also the launch of our Doctoral School, which makes this year’s conference extra special. Once again we have received a tremendous contribution from our postgraduate research community; with over 100 presenters, the conference truly showcases a vibrant PGR community at Salford. These abstracts provide a taster of the research strengths of their works, and provide delegates with a reference point for networking and initiating critical debate. With such wide-ranging topics being showcased, we encourage you to take up this great opportunity to engage with researchers working in different subject areas from your own. To meet global challenges, high impact research inevitably requires interdisciplinary collaboration. This is recognised by all major research funders. Therefore engaging with the work of others and forging collaborations across subject areas is an essential skill for the next generation of researchers