Measuring follow-up time in routinely-collected health datasets: Challenges and solutions

A key requirement for longitudinal studies using routinely-collected health data is to be able to measure what individuals are present in the datasets used, and over what time period. Individuals can enter and leave the covered population of administrative datasets for a variety of reasons, including both life events and characteristics of the datasets themselves. An automated, customizable method of determining individuals' presence was developed for the primary care dataset in Swansea University's SAIL Databank. The primary care dataset covers only a portion of Wales, with 76% of practices participating. The start and end date of the data varies by practice. Additionally, individuals can change practices or leave Wales. To address these issues, a two step process was developed. First, the period for which each practice had data available was calculated by measuring changes in the rate of events recorded over time. Second, the registration records for each individual were simplified. Anomalies such as short gaps and overlaps were resolved by applying a set of rules. The result of these two analyses was a cleaned set of records indicating start and end dates of available primary care data for each individual. Analysis of GP records showed that 91.0% of events occurred within periods calculated as having available data by the algorithm. 98.4% of those events were observed at the same practice of registration as that computed by the algorithm. A standardized method for solving this common problem has enabled faster development of studies using this data set. Using a rigorous, tested, standardized method of verifying presence in the study population will also positively influence the quality of research

Differential Proteomic Analysis of Arabidopsis thaliana Genotypes Exhibiting Resistance or Susceptibility to the Insect Herbivore, Plutella xylostella

A proteomic study was conducted to investigate physiological factors affecting feeding behaviour by larvae of the insect, Plutella xylostella, on herbivore-susceptible and herbivore-resistant Arabidopsis thaliana. The leaves of 162 recombinant inbred lines (Rils) were screened to detect genotypes upon which Plutella larvae fed least (P. xylostella-resistant) or most (P. xylostella-susceptible). 2D-PAGE revealed significant differences in the proteomes between the identified resistant and susceptible Rils. The proteomic results, together with detection of increased production of hydrogen peroxide in resistant Rils, suggest a correlation between P. xylostella resistance and the production of increased levels of reactive oxygen species (ROS), in particular H2O2, and that this was expressed prior to herbivory. Many of the proteins that were more abundant in the Plutella-resistant Rils are known in other biological systems to be involved in limiting ROS damage. Such proteins included carbonic anhydrases, malate dehydrogenases, glutathione S-transferases, isocitrate dehydrogenase-like protein (R1), and lipoamide dehydrogenase. In addition, patterns of germin-like protein 3 isoforms could also be indicative of higher levels of reactive oxygen species in the resistant Rils. Consistent with the occurrence of greater oxidative stress in the resistant Rils is the observation of greater abundance in susceptible Rils of polypeptides of the photosynthetic oxygen-evolving complex, which are known to be damaged under oxidative stress. The combined results suggest that enhanced production of ROS may be a major pre-existing mechanism of Plutella resistance in Arabidopsis, but definitive corroboration of this requires much further work

Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptors

Peer reviewedPublisher PD

What is an admission? A standardised approach to classifying inpatient episode data from multiple jurisdictions

Introduction Inpatient datasets in the UK are primarily organised by episodes (periods of care under an individual consultant), while researchers often want to measure admissions (periods of stay in hospital). We developed a standardized method for identifying admissions in inpatient data, while accounting for differences between the four UK nations. Objectives and Approach All UK inpatient datasets include date variables, permitting chronological sequencing of episodes. They include flags describing whether an episode is a transfer of care, although structures and definitions differ. Data quality is variable leading to concurrent and overlapping episodes, duplication and “orphan” or “childless” transfer episodes, where no originating or destination episode can be identified. Our objective was to define a method for classifying individual episodes into a continuous period of stay in hospital, which would be consistently applicable to the analysis of inpatient datasets of all four UK nations, while prioritising clinical meaningfulness. Three permutations were considered. Results For each permutation, episodes for an individual were linked when they related to the same individual and met the following criteria: • Zero or one day gap between episode end and subsequent episode start • Evidence of transfer according to admission method or discharge destination variables • Episode overlapping or completely nested within another episode Permutations: • a and b • a only • a and c Permutation three was adopted, as it was felt to be the most clinically meaningful approach, was not dependent on accurate recording of transfers and captured nested or overlapping episodes, which may occur for example when a patient is in a long-stay psychiatric or elderly care ward but requires care from a different specialty. Importantly it permitted consistent analysis of episodes across all UK nations. Conclusion/Implications The output of this work provides a useful guide for the classification of inpatient episodes into more clinically meaningful periods of care, and is applicable to the inpatient datasets of all four UK nations. It describes important issues to consider when classifying episodes of care, particularly relating to data quality

Educational outcomes of children with cerebral palsy

Introduction Children with special educational needs (SEN) are more likely to have disadvantaged backgrounds than their peers, attend school less and do not achieve as well academically. Many children with a cerebral palsy (CP) have SEN but little is known about their educational outcomes. Objectives and Approach To investigate the background of children in Wales with CP and describe their educational experience including: type of SEN and SEN provision; school attendance; achievement—teacher assessments at the end of the Foundation Phase and Key Stages 2 and 3 of the National Curriculum (NC)— and in General Certificate of Secondary Education (GCSE) examinations. Data from the Pupil Level Annual School Census (PLASC), NC and GCSE results were linked with routine e-health records of primary and secondary health care data held in SAIL. Using health care records for everyone aged between 0-25 in 2004–14, cases of CP were flagged. Results The linked data set included some 1500–2000 children per school census classified as having a CP, representing a prevalence of some 0.3%. Provisionally, results show: prevalence of CP is higher amongst children living in relatively deprived areas; around 60% of CP children have a statement of SEN; the SEN type most commonly recorded for CP children with SEN is ‘Physical and medical difficulties’ and relatively high proportions have profound, multiple or severe learning difficulties; around 30% of CP children are educated in special schools; CP children in main stream (primary, middle and secondary) schools tended to miss more school sessions (~50% more) than other children and lower percentages achieved the expected levels at key stages 2 and 3 and the Level 2 GCSE threshold. Conclusion/Implications This work demonstrates the utility of record-linkage for providing information to parents, carers and policymakers about education outcomes for this group of children to inform planning and service provision

Regulation of CHK1 inhibitor resistance by a c-Rel and USP1 dependent pathway

AbstractWe previously discovered that deletion of c-Rel in the Eμ-Myc mouse model of lymphoma results in earlier onset of disease, a finding that contrasted with the expected function of this NF-κB subunit in B-cell malignancies. Here we report that c-rel -/- Eµ-Myc cells have an unexpected and major defect in the CHK1 pathway, with almost undetectable levels of CHK1 and CLSPN protein leading to therapeutic resistance to the highly specific CHK1 inhibitor (CHK1i) CCT244747. Similar downregulation of CHK1 levels was also seen in CCT244747 resistant U20S osteosarcoma cells. Further investigation revealed that downregulation of the deubiquitinase USP1 is responsible, at least in part, for these effects. Importantly, we demonstrate that c-rel -/- Eµ-Myc lymphoma cells survive though upregulation of compensatory PI3K/AKT pathway activity. Moreover, targeting this pathway with Pictilisib (GDC-0941) effectively killed c-rel -/- Eµ-Myc in vivo, while having no effect on wild type Eμ-Myc cells. This data reveals an NF-κB regulated pathway controlling CHK1 activity in cancer cells and identifies a potential mechanism for both acquiring and overcoming CHK1i resistance in cancer patients.</jats:p