Comparing uptake across breast, cervical and bowel screening at an individual level:a retrospective cohort study

Funding: CR-UK through its National Awareness & Early Diagnosis Initiative C9227/A17676.Background We investigated demographic and clinical predictors of lower participation in bowel screening relative to breast and cervical screening. Methods Data linkage study of routinely collected clinical data from 430,591 women registered with general practices in the Greater Glasgow & Clyde Health Board. Participation in the screening programmes was measured by attendance at breast or cervical screening or the return of a bowel screening kit. Results 72.6% of 159,993 women invited attended breast screening, 80.7% of 309,899 women invited attended cervical screening and 61.7% of 180,408 women invited completed bowel screening. Of the 68,324 women invited to participate in all three screening programmes during the study period, 52.1% participated in all three while 7.2% participated in none. Women who participated in breast (OR = 3.34 (3.21, 3.47), p < 0.001) or cervical (OR = 3.48 (3.32, 3.65), p < 0.001) were more likely to participate in bowel screening. Conclusion Participation in bowel screening was lower than breast or cervical for this population although the same demographic factors were associated with uptake, namely lower social deprivation, increasing age, low levels of comorbidity and prior non-malignant neoplasms. As women who complete breast and cervical are more likely to also complete bowel screening, interventions at these procedures to encourage bowel screening participation should be explored.Publisher PDFPeer reviewe

Informatics for Health 2017 : advancing both science and practice

Conference report, The Informatics for Health congress, 24-26 April 2017, in Manchester, UK.Introduction : The Informatics for Health congress, 24-26 April 2017, in Manchester, UK, brought together the Medical Informatics Europe (MIE) conference and the Farr Institute International Conference. This special issue of the Journal of Innovation in Health Informatics contains 113 presentation abstracts and 149 poster abstracts from the congress. Discussion : The twin programmes of “Big Data” and “Digital Health” are not always joined up by coherent policy and investment priorities. Substantial global investment in health IT and data science has led to sound progress but highly variable outcomes. Society needs an approach that brings together the science and the practice of health informatics. The goal is multi-level Learning Health Systems that consume and intelligently act upon both patient data and organizational intervention outcomes. Conclusions : Informatics for Health demonstrated the art of the possible, seen in the breadth and depth of our contributions. We call upon policy makers, research funders and programme leaders to learn from this joined-up approach.Publisher PDFPeer reviewe

Trajectories in chronic disease accrual and mortality across the lifespan in Wales, UK (2005-2019), by area deprivation profile : linked electronic health records cohort study on 965,905 individuals

Funding: This work was supported by Health Data Research UK (HDRUK) Measuring and Understanding Multimorbidity using Routine Data in the UK (MUrMuRUK, HDR-9006; CFC0110). Health Data Research UK (HDR-9006) is funded by: UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, the National Institute for Health Research (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation, and Wellcome Trust. This work also was co-funded by the Medical Research Council (MRC) and the National Institute for Health Research (NIHR) through grant number MR/S027750/1. The work was supported by the ADR Wales programme of work, part of the Economic and Social Research Council (part of UK Research and Innovation) funded ADR UK (grant ES/S007393/1).Background  Understanding and quantifying the differences in disease development in different socioeconomic groups of people across the lifespan is important for planning healthcare and preventive services. The study aimed to measure chronic disease accrual, and examine the differences in time to individual morbidities, multimorbidity, and mortality between socioeconomic groups in Wales, UK. Methods  Population-wide electronic linked cohort study, following Welsh residents for up to 20 years (2000-2019). Chronic disease diagnoses were obtained from general practice and hospitalisation records using the CALIBER disease phenotype register. Multi-state models were used to examine trajectories of accrual of 132 diseases and mortality, adjusted for sex, age and area-level deprivation. Restricted mean survival time was calculated to measure time spent free of chronic disease(s) or mortality between socioeconomic groups. Findings  In total, 965,905 individuals aged 5-104 were included, from a possible 2·9m individuals following a 5-year clearance period, with an average follow-up of 13·2 years (12·7 million person-years). Some 673,189 (69·7 %) individuals developed at least one chronic disease or died within the study period. From ages 10 years upwards, the individuals living in the most deprived areas consistently experienced reduced time between health states, demonstrating accelerated transitions to first and subsequent morbidities and death compared to their demographic equivalent living in the least deprived areas. The largest difference were observed in 10 and 20 year old males developing multimorbidity (-0·45 years (99%CI:-0·45,-0·44)) and in 70 year old males dying after developing multimorbidity (-1·98 years (99%CI:-2·01,-1·95)). Interpretation  This study adds to the existing literature on health inequalities by demonstrating that individuals living in more deprived areas consistently experience accelerated time to diagnosis of chronic disease and death across all ages, accounting for competing risks.Publisher PDFPeer reviewe

COVID-19 hospital admissions and deaths after BNT162b2 and ChAdOx1 nCoV-19 vaccinations in 2·57 million people in Scotland (EAVE II):a prospective cohort study

EAVE II is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE—The Health Data Research Hub for Respiratory Health [MC_PC_19004], which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. UA, CM, AA-L, and AFF acknowledge funding from Chief Scientist Office Rapid Research in COVID-19 programme (COV/SAN/20/06) and Health Data Research UK (measuring and understanding multimorbidity using routine data in the UK—HDR-9006; CFC0110). SVK acknowledges funding from a NHS Research Scotland Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_00022/2), and the Scottish Government's Chief Scientist Office (SPHSU17). SJS is funded by a Wellcome Trust Clinical Career Development Fellowship (209560/Z/17/Z).Background  The UK COVID-19 vaccination programme has prioritised vaccination of those at the highest risk of COVID-19 mortality and hospitalisation. The programme was rolled out in Scotland during winter 2020–21, when SARS-CoV-2 infection rates were at their highest since the pandemic started, despite social distancing measures being in place. We aimed to estimate the frequency of COVID-19 hospitalisation or death in people who received at least one vaccine dose and characterise these individuals. Methods  We conducted a prospective cohort study using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) national surveillance platform, which contained linked vaccination, primary care, RT-PCR testing, hospitalisation, and mortality records for 5·4 million people (around 99% of the population) in Scotland. Individuals were followed up from receiving their first dose of the BNT162b2 (Pfizer–BioNTech) or ChAdOx1 nCoV-19 (Oxford–AstraZeneca) COVID-19 vaccines until admission to hospital for COVID-19, death, or the end of the study period on April 18, 2021. We used a time-dependent Poisson regression model to estimate rate ratios (RRs) for demographic and clinical factors associated with COVID-19 hospitalisation or death 14 days or more after the first vaccine dose, stratified by vaccine type. Findings Between Dec 8, 2020, and April 18, 2021, 2 572 008 individuals received their first dose of vaccine—841 090 (32·7%) received BNT162b2 and 1 730 918 (67·3%) received ChAdOx1. 1196 (<0·1%) individuals were admitted to hospital or died due to COVID-19 illness (883 hospitalised, of whom 228 died, and 313 who died due to COVID-19 without hospitalisation) 14 days or more after their first vaccine dose. These severe COVID-19 outcomes were associated with older age (≥80 years vs 18–64 years adjusted RR 4·75, 95% CI 3·85–5·87), comorbidities (five or more risk groups vs less than five risk groups 4·24, 3·34–5·39), hospitalisation in the previous 4 weeks (3·00, 2·47–3·65), high-risk occupations (ten or more previous COVID-19 tests vs less than ten previous COVID-19 tests 2·14, 1·62–2·81), care home residence (1·63, 1·32–2·02), socioeconomic deprivation (most deprived quintile vs least deprived quintile 1·57, 1·30–1·90), being male (1·27, 1·13–1·43), and being an ex-smoker (ex-smoker vs non-smoker 1·18, 1·01–1·38). A history of COVID-19 before vaccination was protective (0·40, 0·29–0·54). Interpretation COVID-19 hospitalisations and deaths were uncommon 14 days or more after the first vaccine dose in this national analysis in the context of a high background incidence of SARS-CoV-2 infection and with extensive social distancing measures in place. Sociodemographic and clinical features known to increase the risk of severe disease in unvaccinated populations were also associated with severe outcomes in people receiving their first dose of vaccine and could help inform case management and future vaccine policy formulation.Publisher PDFPeer reviewe

Investigating the uptake, effectiveness and safety of COVID-19 vaccines : protocol for an observational study using linked UK national data

Funding: This research is part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (HDRUK2020.146). EAVE II is funded by the Medical Research Council (MC_PC_19075) and supported by the Scottish Government. This work is supported by BREATHE - The Health Data Research Hub for Respiratory Health (MC_PC_19004). BREATHE is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. ConCOV is supported by the Medical Research Council (MR/V028367/1); Health Data Research UK (HDR-9006) which receives its funding from the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation (BHF) and the Wellcome Trust; and Administrative Data Research UK which is funded by the Economic and Social Research Council (grant ES/S007393/1).Introduction : The novel coronavirus SARS-CoV-2, which emerged in December 2019, has caused millions of deaths and severe illness worldwide. Numerous vaccines are currently under development of which a few have now been authorised for population-level administration by several countries. As of 20 September 2021, over 48 million people have received their first vaccine dose and over 44 million people have received their second vaccine dose across the UK. We aim to assess the uptake rates, effectiveness, and safety of all currently approved COVID-19 vaccines in the UK. Methods and analysis : We will use prospective cohort study designs to assess vaccine uptake, effectiveness and safety against clinical outcomes and deaths. Test-negative case–control study design will be used to assess vaccine effectiveness (VE) against laboratory confirmed SARS-CoV-2 infection. Self-controlled case series and retrospective cohort study designs will be carried out to assess vaccine safety against mild-to-moderate and severe adverse events, respectively. Individual-level pseudonymised data from primary care, secondary care, laboratory test and death records will be linked and analysed in secure research environments in each UK nation. Univariate and multivariate logistic regression models will be carried out to estimate vaccine uptake levels in relation to various population characteristics. VE estimates against laboratory confirmed SARS-CoV-2 infection will be generated using a generalised additive logistic model. Time-dependent Cox models will be used to estimate the VE against clinical outcomes and deaths. The safety of the vaccines will be assessed using logistic regression models with an offset for the length of the risk period. Where possible, data will be meta-analysed across the UK nations. Ethics and dissemination : We obtained approvals from the National Research Ethics Service Committee, Southeast Scotland 02 (12/SS/0201), the Secure Anonymised Information Linkage independent Information Governance Review Panel project number 0911. Concerning English data, University of Oxford is compliant with the General Data Protection Regulation and the National Health Service (NHS) Digital Data Security and Protection Policy. This is an approved study (Integrated Research Application ID 301740, Health Research Authority (HRA) Research Ethics Committee 21/HRA/2786). The Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub meets NHS Digital’s Data Security and Protection Toolkit requirements. In Northern Ireland, the project was approved by the Honest Broker Governance Board, project number 0064. Findings will be made available to national policy-makers, presented at conferences and published in peer-reviewed journals.Publisher PDFPeer reviewe

Tamoxifen metabolism predicts drug concentrations and outcome in premenopausal patients with early breast cancer

Tamoxifen is the standard-of-care treatment for estrogen receptor-positive premenopausal breast cancer. We examined tamoxifen metabolism via blood metabolite concentrations and germline variations of CYP3A5, CYP2C9, CYP2C19 and CYP2D6 in 587 premenopausal patients (Asians, Middle Eastern Arabs, Caucasian-UK; median age 39 years) and clinical outcome in 306 patients. N-desmethyltamoxifen (DM-Tam)/(Z)-endoxifen and CYP2D6 phenotype significantly correlated across ethnicities (R2: 53%, P&lt;10?77). CYP2C19 and CYP2C9 correlated with norendoxifen and (Z)-4-hydroxytamoxifen concentrations, respectively (P&lt;0.001). DM-Tam was influenced by body mass index (P&lt;0.001). Improved distant relapse-free survival (DRFS) was associated with decreasing DM-Tam/(Z)-endoxifen (P=0.036) and increasing CYP2D6 activity score (hazard ratio (HR)=0.62; 95% confidence interval (CI), 0.43–0.91; P=0.013). Low (&lt;14?nM) compared with high (&gt;35?nM) endoxifen concentrations were associated with shorter DRFS (univariate P=0.03; multivariate HR=1.94; 95% CI, 1.04–4.14; P=0.064). Our data indicate that endoxifen formation in premenopausal women depends on CYP2D6 irrespective of ethnicity. Low endoxifen concentration/formation and decreased CYP2D6 activity predict shorter DRFS

Statin use is not associated with future long-term care admission - extended follow-up of two randomised controlled trials

Background: Statins have been associated with later life, long-term care admission in observational studies. However, by preventing vascular events, statins may also prevent or delay admission. We wished to determine statin and long-term care admission associations in a randomised controlled trial context, and describe associations between long-term care admission and other clinical and demographic factors. Methods: We used extended follow-up of two randomised trial populations, using national data to assign the long-term care admission outcome, and included individuals screened or recruited to two large randomised trials of pravastatin 40 mg daily—the West of Scotland Coronary Prevention Study (WOSCOPS) and the pravastatin in elderly individuals at risk of vascular disease (PROSPER) study. We described univariable and multivariable analyses of potential predictors of long-term care admission with corresponding survival curves of incident long-term care admission and analyses adjusted for competing risk. Results: In total 11,015 (10%) of the trial participants were admitted to long-term care. There was no difference between participants in the statin or placebo arms of either trial in regard to admissions to long-term care. On multivariable analyses, independent associations with incident long-term care admission in the PROSPER trial were age (hazard ratio [HR] 1.06 per year, 95% confidence interval [CI] 1.03–1.09) and male sex (HR 0.72, 95% CI 0.53–0.99). In the WOSCOPS, age (HR 1.12 per year, 95% CI 1.10–1.13) and increasing social deprivation (HR 1.05, 95% CI 1.03–1.08) were associated with incident long-term care admission. Conclusion: We did not demonstrate an association between historical statin use and future long-term care admission. The strongest associations with incident long-term care admission were non-modifiable factors of age, sex and socioeconomic deprivation

Undergraduate orientations towards higher education in Germany and England: problematizing the notion of ‘student as customer’

There is a great deal of discussion in the academic literature around how the current conditions in higher education frame students as customers. Observers are of the view that rankings and marketing, an increased focus on student satisfaction, and particularly tuition fees, encourage an instrumental, passive attitude towards a university education. Given the volume of attention directed towards this topic, it is perhaps surprising that there is relatively little scholarship that examines it empirically. Some who have addressed it presumed a customer/consumer orientation in students and have been somewhat—but not entirely successful—in generating evidence to confirm those assumptions. It appears that the expectations of this instrumental, passive orientation are being realised in part, but that this is also mediated by other dispositions. What could be considered to be missing from the analysis thus far is an exploration of how students make university­related decisions (not simply what choices are based on) and how they understand the respective roles of the student and university. This study begins to fill that gap, exploring the orientations towards university of undergraduates in Germany and England, two countries where the diffusion of market conditions in higher education policies has been somewhat contrasting. Distinctions between the German and English students did emerge, but these were less based on those countries’ unequal engagement with tuition fees and rankings and more to do with other aspects of their university cultures and the world beyond their degrees. This suggests that how people approach their time as students is more complex than some of the literature assumes. Furthermore, at the very least, any consideration of this topic must include an analysis of how students themselves understand and experience their higher education and broader social contexts

Crack Tip Opening Angle: Measurement and Modeling of Fracture Resistance in Low and High Strength Pipeline Steels

Crack tip opening angle (CTOA) is becoming one of the more widely accepted properties for characterizing fully plastic fracture. In fact, it has been recognized as a measure of the resistance of a material to fracture, in cases where there is a large degree of stable-tearing crack extension during the fracture process. This type of steady-state fracture resistance takes place when the CTOA in a material reaches a critical value, as typically occurs in low-constraint configurations. Our current research has applied the CTOA concept as an alternative or an addition to the Charpy V-notch and the drop weight tear test (DWTT) fracture energy in pipeline characterization. A test technique for direct measurement of CTOA was developed, using a modified double cantilever beam (MDCB) specimen. A digital camera and image analysis software are used to record the progression of the crack tip and to estimate CTOA using the crack edges adjacent to the crack tip. A steady-state CTOA has been successfully measured on five different strength grades of gas pipeline steel (four low strength grades and one high strength grade: X100). In addition, two-dimensional finite element models (2D FEMs) are used to demonstrate the sequence of the fracture process and the deformation mechanisms involved. The CTOA measurements and models are correlated and agree well.Copyright © 2006 by ASM

A bankközi likviditási többlet hatása a vállalati és bankközi kamatokra

Pre-eclampsia (PE) is a serious complication of pregnancy with potentially life threatening consequences for both mother and baby. Presently there is no test with the required performance to predict which healthy first-time mothers will go on to develop PE. The high specificity, sensitivity, and multiplexed nature of selected reaction monitoring holds great potential as a tool for the verification and validation of putative candidate biomarkersfor disease states. Realization of this potential involves establishing a high throughput, cost effective, reproducible sample preparation workflow. We have developed a semiautomated HPLC-based sample preparation workflow before a label-free selected reaction monitoring approach. This workflow has been applied to the search for novel predictive biomarkers for PE. To discover novel candidate biomarkers for PE, we used isobaric tagging to identify several potential biomarker proteins in plasma obtained at 15 weeks gestation from nulliparous women who later developed PE compared with pregnant women who remained healthy. Such a study generates a number of "candidate" biomarkers that require further testing in larger patient cohorts. As proof-of-principle, two of these proteins were taken forward for verification in a 100 women (58 PE, 42 controls) using label-free SRM. We obtained reproducible protein quantitation across the 100 samples and demonstrated significant changes in protein levels, even with as little as 20% change in protein concentration. The SRM data correlated with a commercial ELISA, suggesting that this is a robust workflow suitable for rapid, affordable, label-free verification of which candidate biomarkers should be taken forward for thorough investigation. A subset of pregnancyspecific glycoproteins (PSGs) had value as novel predictive markers for PE.Richard T. Blankley, Christal Fisher, Melissa Westwood, Robyn North, Philip N. Baker, Michael J. Walker, Andrew Williamson, Anthony D. Whetton, Wanchang Lin, Lesley McCowan, Claire T. Roberts, Garth J. S. Cooper, Richard D. Unwin, and Jenny E. Myer