Professor Simon de Lusignan

The Translational Research and Patients safety in Europe (TRANSFoRm) project aims to integrate primary care with clinical research whilst improving patient safety. The TRANSFoRm International Research Readiness survey (TIRRE) aims to demonstrate data use through two linked data studies and by identifying clinical data repositories and genetic databases or disease registries prepared to participate in linked research. The TIRRE survey collects data at micro-, meso- and macro-levels of granularity; to fulfil data, study specific, business, geographical and readiness requirements of potential data providers for the TRANSFoRm demonstration studies. We used descriptive statistics to differentiate between demonstration-study compliant and non-compliant repositories. We only included surveys with >70% of questions answered in our final analysis, reporting the odds ratio (OR) of positive responses associated with a demonstration-study compliant data provider. We contacted 531 organisations within the Eurpean Union (EU). Two declined to supply information; 56 made a valid response and a further 26 made a partial response. Of the 56 valid responses, 29 were databases of primary care data, 12 were genetic databases and 15 were cancer registries. The demonstration compliant primary care sites made 2098 positive responses compared with 268 in non-use-case compliant data sources [OR: 4.59, 95% confidence interval (CI): 3.93-5.35, p < 0.008]; for genetic databases: 380:44 (OR: 6.13, 95% CI: 4.25-8.85, p < 0.008) and cancer registries: 553:44 (OR: 5.87, 95% CI: 4.13-8.34, p < 0.008). TIRRE comprehensively assesses the preparedness of data repositories to participate in specific research projects. Multiple contacts about hypothetical participation in research identified few potential sites.

A patient would contract surface muscles as a reaction called muscle guarding when experiencing discomfort and pain during physical palpation. This reaction carries important information about an affected location. Training physicians to regulate palpation forces to elicit just enough muscle tension is a challenge using real patients. Tunable stiffness mechanisms enabled by soft robotics can be effectively integrated into medical simulator designs for effective clinical education. In this paper, we propose a controllable stiffness muscle layer to simulate guarding for abdominal palpation training. Designs with soft, fine, and rigid granular jamming, stretchable and non-stretchable layer jamming mechanisms were tested and evaluated as methods to create controllable stiffness muscle. User studies have been carried out on 10 naive participants to differentiate the tense and relaxed abdomen with the proposed jamming mechanisms. Muscle samples made of ground coffee (fine granular jamming) and latex layers (stretchable layer jamming) show good usability in simulating abdomen with different stiffness with at least 75% of the user data exhibits more than 70% of decision accuracy for both tested palpation gestures (single finger and multiple fingers) after short pre-training.

Background: Since the start of the COVID-19 pandemic, efforts have been made to develop early warning risk scores to help clinicians decide which patient is likely to deteriorate and require hospitalization. The RECAP (Remote COVID-19 Assessment in Primary Care) study investigates the predictive risk of hospitalization, deterioration, and death of patients with confirmed COVID-19, based on a set of parameters chosen through a Delphi process performed by clinicians. We aim to use rich data collected remotely through the use of electronic data templates integrated in the electronic health systems of several general practices across the United Kingdom to construct accurate predictive models. The models will be based on preexisting conditions and monitoring data of a patient's clinical parameters (eg, blood oxygen saturation) to make reliable predictions as to the patient's risk of hospital admission, deterioration, and death. Objective: This statistical analysis plan outlines the statistical methods to build the prediction model to be used in the prioritization of patients in the primary care setting. The statistical analysis plan for the RECAP study includes the development and validation of the RECAP-V1 prediction model as a primary outcome. This prediction model will be adapted as a three-category risk score split into red (high risk), amber (medium risk), and green (low risk) for any patient with suspected COVID-19. The model will predict the risk of deterioration and hospitalization. Methods: After the data have been collected, we will assess the degree of missingness and use a combination of traditional data imputation using multiple imputation by chained equations, as well as more novel machine-learning approaches to impute the missing data for the final analysis. For predictive model development, we will use multiple logistic regression analyses to construct the model. We aim to recruit a minimum of 1317 patients for model development and validation. We will then externally validate the model on an independent dataset of 1400 patients. The model will also be applied for multiple different datasets to assess both its performance in different patient groups and its applicability for different methods of data collection. Results: As of May 10, 2021, we have recruited 3732 patients. A further 2088 patients have been recruited through the National Health Service Clinical Assessment Service, and approximately 5000 patients have been recruited through the DoctalyHealth platform. Conclusions: The methodology for the development of the RECAP-V1 prediction model as well as the risk score will provide clinicians with a statistically robust tool to help prioritize COVID-19 patients.

The analysis of primary care data plays an important role in understanding health at an individual and population level. Currently the utilization of computerized medical records is low due to the complexities, heterogeneities and veracity associated with these data. We present a deep learning methodology that clusters 11,000 records in an unsupervised manner identifying non-linear patterns in the data. This provides a useful tool for visualization as well as identify features driving the formation of clusters. Further analysis reveal the features that differentiate sub-groups that can aid clinical decision making. Our results uncover subsets that contain the highest proportion of missing data, specifically Episode type, as well as the sources that provide the most complete data.

In UK general practice, the coding of clinical data (Read Coding) is far from universal. This study set out to examine the barriers to recording structured information in computerised medical records; and to explore whether managers and clinicians had different perspectives in how these barriers should be overcome.

UK primary care records are computerised and these records are used for both research and quality improvement. However, there is disparity in the prevalence of diabetes found in epidemiological studies compared with that reported through the UK's national quality improvement scheme.

To create practical recommendations for the curation of routinely collected health data and artificial intelligence (AI) in primary care with a focus on ensuring their ethical use. We defined data curation as the process of management of data throughout its lifecycle to ensure it can be used into the future. We used a literature review and Delphi exercises to capture insights from the Primary Care Informatics Working Group (PCIWG) of the International Medical Informatics Association (IMIA). We created six recommendations: (1) Ensure consent and formal process to govern access and sharing throughout the data life cycle; (2) Sustainable data creation/collection requires trust and permission; (3) Pay attention to Extract-Transform-Load (ETL) processes as they may have unrecognised risks; (4) Integrate data governance and data quality management to support clinical practice in integrated care systems; (5) Recognise the need for new processes to address the ethical issues arising from AI in primary care; (6) Apply an ethical framework mapped to the data life cycle, including an assessment of data quality to achieve effective data curation. The ethical use of data needs to be integrated within the curation process, hence running throughout the data lifecycle. Current information systems may not fully detect the risks associated with ETL and AI; they need careful scrutiny. With distributed integrated care systems where data are often used remote from documentation, harmonised data quality assessment, management, and governance is important. These recommendations should help maintain trust and connectedness in contemporary information systems and planned developments.

Introduction Falls are the leading cause of injury in older people. Reducing falls could reduce financial pressures on health services. We carried out this research to develop a falls risk model, using routine primary care and hospital data to identify those at risk of falls, and apply a cost analysis to enable commissioners of health services to identify those in whom savings can be made through referral to a falls prevention service. Methods Multilevel logistical regression was performed on routinely collected general practice and hospital data from 74751 over 65’s, to produce a risk model for falls. Validation measures were carried out. A cost-analysis was performed to identify at which level of risk it would be cost-effective to refer patients to a falls prevention service. 95% confidence intervals were calculated using a Monte Carlo Model (MCM), allowing us to adjust for uncertainty in the estimates of these variables. Results A risk model for falls was produced with an area under the curve of the receiver operating characteristics curve of 0.87. The risk cut-off with the highest combination of sensitivity and specificity was at p = 0.07 (sensitivity of 81% and specificity of 78%). The risk cut-off at which savings outweigh costs was p = 0.27 and the risk cut-off with the maximum savings was p = 0.53, which would result in referral of 1.8% and 0.45% of the over 65’s population respectively. Above a risk cut-off of p = 0.27, costs do not exceed savings. Conclusions This model is the best performing falls predictive tool developed to date; it has been developed on a large UK city population; can be readily run from routine data; and can be implemented in a way that optimises the use of health service resources. Commissioners of health services should use this model to flag and refer patients at risk to their falls service and save resources

Introduction PBC registries in the UK focus on data from secondary care without clear coordinated contribution from primary care. The Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) receives data from > 500 primary care practices (PCPs). Notably, the Lancet commissioning group is extracting data from the RCGP RSC database to shape UK policy on liver disease. Aims To create a novel ontology to facilitate PBC case finding from primary care provider (PCP) records. Methods RCGP RSC data were collected from participating PCPs in the county of Surrey, UK. PBC diagnostic criteria of the AASLD and EASL guidelines were used to develop 725 data codes to facilitate patient record searches. A scoring system built into the ontology allowed categorization of cases as PBC definite, PBC probable, and PBC unlikely. Results A total of 218,099 records were searched from participating PCPs. Of these, there were 58 PBC definite, 2317 PBC probable, and 215,724 PBC unlikely patients. There were 32 PBC definite patients who did not match to our regional PBC database and were henceforth included as new-found cases. Two of these cases were not labeled as PBC by the PCP. From the PBC unlikely group, 7/215,724 (0.003%) patients were labeled as PBC in secondary care records; however, none of them were coded as having PBC by their PCPs. Conclusions Utilization of the UK National RCGP RSC database supported by novel ontology score has successfully helped us identify (i) new cases of PBC not known to local/regional secondary care providers and (ii) de novo PBC cases. There are many PBC probable cases whose data merit further careful evaluation.

Objective To appraise and synthesise research on the impact of physician assistants/associates (PA) in secondary care, specifically acute internal medicine, care of the elderly, emergency medicine, trauma and orthopaedics, and mental health. Design Systematic review. Setting Electronic databases (Medline, Embase, ASSIA, CINAHL, SCOPUS, PsycINFO, Social Policy and Practice, EconLit and Cochrane), reference lists and related articles. Included articles Peer-reviewed articles of any study design, published in English, 1995–2017. Interventions Blinded parallel processes were used to screen abstracts and full text, data extractions and quality assessments against published guidelines. A narrative synthesis was undertaken. Outcome measures Impact on: patients’ experiences and outcomes, service organisation, working practices, other professional groups and costs. Results 5472 references were identified and 161 read in full; 16 were included—emergency medicine (7), trauma and orthopaedics (6), acute internal medicine (2), mental health (1) and care of the elderly (0). All studies were observational, with variable methodological quality. In emergency medicine and in trauma and orthopaedics, when PAs are added to teams, reduced waiting and process times, lower charges, equivalent readmission rate and good acceptability to staff and patients are reported. Analgesia prescribing, operative complications and mortality outcomes were variable. In internal medicine outcomes of care provided by PAs and doctors were equivalent. Conclusions PAs have been deployed to increase the capacity of a team, enabling gains in waiting time, throughput, continuity and medical cover. When PAs were compared with medical staff, reassuringly there was little or no negative effect on health outcomes or cost. The difficulty of attributing cause and effect in complex systems where work is organised in teams is highlighted. Further rigorous evaluation is required to address the complexity of the PA role, reporting on more than one setting, and including comparison between PAs and roles for which they are substituting.

Background The consequences of poorly managed hearing loss can be ameliorated with hearing aid use but rates of use are sub-optimal. The impact of audiologist behaviour on subsequent use, particularly over the long term, is unknown. Purpose This study aimed to describe the role of the behaviour change wheel in developing an intervention to introduce and embed particular clinical behaviours into adult hearing aid fitting consultations, within the framework of the Medical Research Council guidance on complex interventions. Methods Following the steps of the behaviour change wheel, audiologist behaviours that might influence hearing aid use were identified based on a systematic review and qualitative work with audiologists. An analysis, using the COM-B model, identified potential drivers of the target behaviours. This was used to select intervention functions and behaviour change techniques likely to influence behaviour in this context. Results The target behaviours were as follows: giving information about the benefits of hearing aid use and the negative consequences of non-use, providing prompts for use and engaging in collaborative behavioural planning for use. The behavioural analysis suggested that psychological capability, opportunity and motivation were potential drivers of these behaviours. The intervention functions of education, coercion, training, environmental restructuring, modelling and enablement were selected and combined to develop a single complex intervention that seeks to address the target behaviours. Conclusions This is the first study to use the behaviour change wheel to develop a complex intervention in the context of audiology. The theory-based development of the intervention will facilitate evaluation of its feasibility and effectiveness.

Objective Allergic rhinitis (AR) is a global health problem, potentially impacting individuals’ sleep, work and social life. We aimed to use a surveillance network of general practitioners (GPs) to describe the epidemiology of AR consultations in England. Setting A large GP surveillance network covering approximately 53% of the English population. Methods GP consultations for AR across England between 30 December 2002 and 31 December 2014 were analysed. Using more granular data available between 2 April 2012 and 31 December 2014 rates and rate ratios (RR) of AR were further analysed in different age groups, gender, rural-urban classification and index of multiple deprivation score quintile of location of GP. Results The mean weekly rate for AR consultations was 19.8 consultations per 100 000 GP registered patients (range 1.13–207), with a regular peak occurring during June (weeks 24–26), and a smaller peak during April. Between 1 April 2012 and 31 December 2014, the highest mean daily rates of consultations per 1 00 000 were: in age group 5–14 years (rate=8.02, RR 6.65, 95% CI 6.38 to 6.93); females (rate=4.57, RR 1.12 95% CI 1.12 to 1.13); persons registered at a GP in the most socioeconomically deprived quintile local authority (rate=5.69, RR 1.48, 95% CI 1.47 to 1.49) or in an urban area with major conurbation (rate=5.91, RR 1.78, 95% CI 1.69 to 1.87). Conclusions AR rates were higher in those aged 5–14 years, females and in urban and socioeconomically deprived areas. This needs to be viewed in the context of this study’s limitations but should be considered in health promotion and service planning.

Background: Governments and healthcare providers are keen to find innovative ways to more efficiently deliver care. Interest in e-consultation has grown, but evidence of benefit is uncertain. Objective: Aims: To assess the evidence of delivering e-consultation using secure email/messaging or video links in primary care. Methods: A systematic review was conducted on the use and application of e-consultations in primary care. We searched seven international databases (Medline, Embase, CINAHL, Cochrane Library, PsycINFO, Econlit and Web of Science) (1999-2017), identifying 52 relevant studies. Papers were screened against a detailed inclusion and exclusion criteria. Independent dual data extraction was conducted and assessed for quality. The resulting evidence was synthesised using thematic analysis. Results: This review included fifty-seven (n=57) studies from a range of countries, mainly the USA (n=30) and the UK (n=13). There were disparities in uptake and utilisation towards more use by younger, employed adults. Patient responses to e-consultation were mixed. Patients reported satisfaction with services and improved self-care, communication and engagement with clinicians. Evidence for the acceptability and ease of use was strong, especially for those with long-term conditions and patients located in remote regions. However, patients were concerned about the privacy and security of their data. For primary healthcare staff, e-consultation delivers challenges around time-management, having the correct technological infrastructure, whether it offers a comparable standard of clinical quality, and whether it improves health outcomes. Conclusions: E-consultations may improve aspects of care delivery, but the small scale of many of the studies and low adoption rates leaves unanswered questions about usage, quality, cost and sustainability. We need to improve e-consultation implementation, demonstrate how e-consultations will not increase disparities in access, provide better reassurance to patients about privacy, and incorporate e-consultation as part of a manageable clinical workflow. Clinical Trial: PROSPERO (International Prospective Register of Systematic Reviews) Registration Number: CRD42015019152

Background Chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity and mortality in England, however estimates of its prevalence vary considerably. Routinely collected and coded primary care data can be used to monitor disease prevalence, however reliance upon diagnostic codes alone is likely to miss cases. Methods We devised an ontological approach to COPD case detection and implemented it in a large primary care database to identify definite and probable cases of COPD. We used this to estimate the prevalence of COPD in England. Results Use of this approach to detect definite COPD cases yielded a prevalence of 2.57% (95% CI 2.55–2.60) in the total population, 4.56% (95%CI 4.52–4.61) in those aged ≥ 35 and 5.41% (95% CI 5.36–5.47) in ex or current smokers. The ontological approach identified an additional 10,543 definite cases compared with using diagnostic codes alone. Prevalence estimates were higher than the 1.9% prevalence currently reported by the UK primary care pay for performance (P4P) disease register. COPD prevalence when definite and probable cases were combined was 3.02% (95% CI 3.0–3.05) in the total population, 5.38% (95% CI 5.33–5.42) in those aged ≥ 35 and 6.46% (95% CI 6.46-6.40-6.56) in ex or current smokers. Conclusions We demonstrate a robust reproducible method for COPD case detection in routinely collected primary care data. Our calculated prevalence differed significantly from current estimates based upon P4P data, suggesting that the burden of COPD in England is greater than currently predicted.

Building an evidence base for the effects of different types of staff in general practice is challenging and takes time. McCartney is right to say that no evidence shows that physician associates make a difference to clinician stress and burnout. But more evidence is available than she suggests, which may be important at a time of considerable vacancies for general practitioners and practice nurses.

Background: Patients' access to their computerised medical records (CMRs) is a legal right in many countries. However, little is reported about the benefit-risk associated with patients' online access to their CMRs. Objective: To conduct a consensus exercise to assess the impact of patients' online access to their CMRs on the quality of care as defined in six domains by the Institute of Medicine (IoM), now the National Academy of Medicine (NAM). Method: A five-round Delphi study was conducted. Round One explored experts' (n = 37) viewpoints on providing patients with access to their CMRs. Round Two rated the appropriateness of statements arising from Round One (n = 16). The third round was an online panel discussion of findings (n = 13) with the members of both the International Medical Informatics Association and the European Federation of Medical Informatics Primary Health Care Informatics Working Groups. Two additional rounds, a survey of the revised consensus statements and an online workshop, were carried out to further refine consensus statements. Results: Thirty-seven responses from Round One were used as a basis to initially develop 15 statements which were categorised using IoM's domains of care quality. The experts agreed that providing patients online access to their CMRs for bookings, results, and prescriptions increased efficiency and improved the quality of medical records. Experts also anticipated that patients would proactively use their online access to share data with different health care providers, including emergencies. However, experts differed on whether access to limited or summary data was more useful to patients than accessing their complete records. They thought online access would change recording practice, but they were unclear about the benefit-risk of high and onerous levels of security. The 5-round process, finally, produced 16 consensus statements. Conclusion: Patients' online access to their CMRs should be part of all CMR systems. It improves the process of health care, but further evidence is required about outcomes. Online access improves efficiency of bookings and other services. However, there is scope to improve many of the processes of care it purports to support, particularly the provision of a more effective interface and the protection of the vulnerable.

AIMSWhether diabetes increases venous thromboembolism (VTE) is unclear. Any greater risk may relate to insulin resistance, but many studies did not differentiate between type 1 diabetes and type 2 diabetes for VTE risk. METHODSRetrospective cohort study of the Royal College of General Practitioners Research and Surveillance Centre, comprising over 530 primary care practices. We determined whether type 1 diabetes and/or type 2 diabetes are independent risk factors for VTE. The index date was 1 January 2009, individuals were followed to 31 December 2018, or censoring. Cox proportional hazard regression analysis was used to investigate the risk of VTE in people with type 1 diabetes and type 2 diabetes relative to no diabetes. The primary outcome was occurrence of VTE. The model was adjusted for potential confounders for VTE. RESULTSThere were 7086 people with type 1 diabetes and 95,566 with type 2 diabetes, diagnosed before 1 January 2009. The non-diabetes group consisted of 1,407,699 people. In the unadjusted analysis, there was no increased risk of VTE with type 1 diabetes (HR 1.00, 95% CI 0.76-1.33) but there was for type 2 diabetes (HR 2.70, 95% CI 2.57-2.84). In the fully adjusted model, VTE risk was increased in type 1 diabetes (HR 1.46, 95% CI 1.11-1.92), but not with type 2 diabetes (HR 1.06, 95% CI 0.98-1.14). CONCLUSIONSType 1 diabetes was associated with a greater risk for VTE while type 2 diabetes was not. Further work is needed to determine the reason(s) for this.

Background Randomised controlled trials (RCTs) are the gold standard for evidence-based practice. However, RCTs can have limitations. For example, translation of findings into practice can be limited by design features, such as inclusion criteria, not accurately reflecting clinical populations. In addition, it is expensive to recruit and follow-up participants in RCTs. Linkage with routinely collected data could offer a cost-effective way to enhance the conduct and generalisability of RCTs. The aim of this study is to investigate how primary care data can support RCTs. Methods Secondary analysis following linkage of two datasets: 1) multicentre CHHiP radiotherapy trial (ISRCTN97182923) and 2) primary care database from the Royal College of General Practitioners Research and Surveillance Centre. Comorbidities and medications recorded in CHHiP at baseline, and radiotherapy-related toxicity recorded in CHHiP over time were compared with primary care records. The association of comorbidities and medications with toxicity was analysed with mixed-effects logistic regression. Results Primary care records were extracted for 106 out of 2811 CHHiP participants recruited from sites in England (median age 70, range 44 to 82). Complementary information included longitudinal body mass index, blood pressure and cholesterol, as well as baseline smoking and alcohol usage but was limited by the considerable missing data. In the linked sample, 9 (8%) participants were recorded in CHHiP as having a history of diabetes and 38 (36%) hypertension, whereas primary care records indicated incidence prior to trial entry of 11 (10%) and 40 (38%) respectively. Concomitant medications were not collected in CHHiP but available in primary care records. This indicated that 44 (41.5%) men took aspirin, 65 (61.3%) statins, 14 (13.2%) metformin and 46 (43.4%) phosphodiesterase-5-inhibitors at some point before or after trial entry. Conclusions We provide a set of recommendations on linkage and supplementation of trials. Data recorded in primary care are a rich resource and linkage could provide near real-time information to supplement trials and an efficient and cost-effective mechanism for long-term follow-up. In addition, standardised primary care data extracts could form part of RCT recruitment and conduct. However, this is at present limited by the variable quality and fragmentation of primary care data.

Background and Objective: Obesity is an important contributor to the risk of both asthma and Type 2 Diabetes (T2DM). However, it has been suggested that T2DM and asthma are also independently associated. The aim of this systematic review was to synthesize the evidence for an independent relationship between T2DM and asthma. Methods: MEDLINE and EMBASE were searched for studies reporting the relationship between asthma and T2DM in adults. Given a potential bidirectional relationship, articles relating to T2DM as a risk factor for asthma, and asthma as a risk factor for T2DM were examined separately. Results: Eight studies were identified for inclusion in the review (n=2,934,399 participants). Four studies examined incident diabetes in those with asthma. The pooled (random effects model) adjusted hazard ratio for incident T2DM in asthma was 1.37 (95%CI 1.12-1.69; p ˂0.001) after controlling for BMI. Four studies reported prevalence or incidence rates of asthma in people with T2DM; higher rates of asthma in those with T2DM were reported in all four studies. Meta-analysis of results was not possible due to methodological heterogeneity. The quality of included studies was good, but due to small numbers, publication bias cannot be excluded. Conclusion: The published literature suggests a bidirectional independent relationship between T2DM and asthma, although we cannot exclude publication bias.

Introduction: Determining CKD stage and disease progression based on eGFR in primary care is complicated by the fact that the measurements are irregularly sampled and influenced by both genuine physiological changes and external factors. Models used for these purposes would ideally capture both short- (for staging) and long-term (for progression) trends. However, existing regression algorithms such as linear, polynomial and Gaussian process regression either cannot account for these challenges or do not satisfy the key clinical requirements of providing an easily interpretable model that can elucidate short- and long-term trends. In order to balance interpretability and flexibility, an extension to broken-stick regression models is proposed in order to make them more suitable for modelling clinical time series.

•Current literature on excess mortality during the first wave of COVID-19 is limited.•We report the absolute excess risk (AER) of mortality and excess mortality rate (EMR) for weeks 2 to 20 in 2020 from surveillance network data.•AER of mortality was 197.8 per 10,000 person years.•Being male, older, of black ethnicity, more deprived, and living in a larger household increased EMR.•Presence of comorbidities also increased EMR. Few studies report contributors to the excess mortality in England during the first wave of coronavirus disease 2019 (COVID-19) infection. We report the absolute excess risk (AER) of mortality and excess mortality rate (EMR) from a nationally representative COVID-19 sentinel surveillance network including known COVID-19 risk factors in people aged 45 years and above. Pseudonymised, coded clinical data were uploaded from contributing primary care providers (N = 1,970,314, ≥45years). We calculated the AER in mortality by comparing mortality for weeks 2 to 20 this year with mortality data from the Office for National Statistics (ONS) from 2018 for the same weeks. We conducted univariate and multivariate analysis including preselected variables. We report AER and EMR, with 95% confidence intervals (95% CI). The AER of mortality was 197.8/10,000 person years (95%CI:194.30–201.40). The EMR for male gender, compared with female, was 1.4 (95%CI:1.35–1.44, p

Point-of-care lateral flow device antigen testing has been used extensively to identify individuals with active SARS-CoV-2 infection in the community. This study aimed to evaluate the diagnostic accuracy of two point-of-care tests (POCTs) for SARS-CoV-2 in routine community care. Adults and children with symptoms consistent with suspected current COVID-19 infection were prospectively recruited from 19 UK general practices and two COVID-19 testing centres between October 2020 and October 2021. Participants were tested by trained healthcare workers using at least one of two index POCTs (Roche-branded SD Biosensor Standard™ Q SARS-CoV-2 Rapid Antigen Test and/or BD Veritor™ System for Rapid Detection of SARS-CoV-2). The reference standard was laboratory triplex reverse transcription quantitative PCR (RT-PCR) using a combined nasal/oropharyngeal swab. Diagnostic accuracy parameters were estimated, with 95% confidence intervals (CIs), overall, in relation to RT-PCR cycle threshold and in pre-specified subgroups. Of 663 participants included in the primary analysis, 39.2% (260/663, 95% CI 35.5% to 43.0%) had a positive RT-PCR result. The SD Biosensor POCT had sensitivity 84.0% (178/212, 78.3% to 88.6%) and specificity 98.5% (328/333, 96.5% to 99.5%), and the BD Veritor POCT had sensitivity 76.5% (127/166, 69.3% to 82.7%) and specificity 98.8% (249/252, 96.6% to 99.8%) compared with RT-PCR. Sensitivity of both devices dropped substantially at cycle thresholds ≥30 and in participants more than 7 days after onset of symptoms. Both POCTs assessed exceed the Medicines and Healthcare products Regulatory Agency target product profile's minimum acceptable specificity of 95%. Confidence intervals for both tests include the minimum acceptable sensitivity of 80%. In symptomatic patients, negative results on these two POCTs do not preclude the possibility of infection. Tests should not be expected to reliably detect disease more than a week after symptom onset, when viral load may be reduced. ISRCTN142269.

IntroductionSodium-glucose co-transporter-2 (SGLT2) inhibitors are oral antihyperglycemic agents for the treatment of people with type 2 diabetes (T2DM). Two recent cardiovascular outcome trials (CVOTs), the EMPA-REG OUTCOME trial and CANVAS Program, have demonstrated that SGLT2 inhibitors have cardiovascular benefit in high-risk cardiovascular patients. The aim of our study will be to identify the prevalence of patients in an English primary care setting with the equivalent cardiovascular risk profile to those included in each of four SGLT2 inhibitor CVOTs: CANVAS, DECLARE, EMPA-REG, and VERTIS CV.MethodsRoutinely collected primary care data from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network database will be used. We will perform a cross-sectional analysis to calculate the prevalence of people that have equivalent cardiovascular risk to participants included in each of the four above-mentioned SGLT2 inhibitor CVOTs. The demographic and clinical characteristics of the subgroups will also be compared with participants in each trial. The study cohort will include people with T2DM in the RCGP RSC dataset. Subgroups of people will be identified using Read codes that most closely match the inclusion criteria of each trial. Descriptive statistics will be used to report the characteristics of people at high cardiovascular risk and compared against those of people in each CVOT.Planned OutputsFindings from the study will be submitted for publication in a peer-reviewed journal to report the applicability of each SGLT2 inhibitor trial to real-world clinical practice.FundingAstraZeneca UK Limited.

Accurate assessment of COVID-19 severity in the community is essential for patient care and requires COVID-19-specific risk prediction scores adequately validated in a community setting. Following a qualitative phase to identify signs, symptoms, and risk factors, we aimed to develop and validate two COVID-19-specific risk prediction scores. Remote COVID-19 Assessment in Primary Care-General Practice score (RECAP-GP; without peripheral oxygen saturation [SpO ]) and RECAP-oxygen saturation score (RECAP-O2; with SpO ). RECAP was a prospective cohort study that used multivariable logistic regression. Data on signs and symptoms (predictors) of disease were collected from community-based patients with suspected COVID-19 via primary care electronic health records and linked with secondary data on hospital admission (outcome) within 28 days of symptom onset. Data sources for RECAP-GP were Oxford-Royal College of General Practitioners Research and Surveillance Centre (RCGP-RSC) primary care practices (development set), northwest London primary care practices (validation set), and the NHS COVID-19 Clinical Assessment Service (CCAS; validation set). The data source for RECAP-O2 was the Doctaly Assist platform (development set and validation set in subsequent sample). The two probabilistic risk prediction models were built by backwards elimination using the development sets and validated by application to the validation datasets. Estimated sample size per model, including the development and validation sets was 2880 people. Data were available from 8311 individuals. Observations, such as SpO , were mostly missing in the northwest London, RCGP-RSC, and CCAS data; however, SpO was available for 1364 (70·0%) of 1948 patients who used Doctaly. In the final predictive models, RECAP-GP (n=1863) included sex (male and female), age (years), degree of breathlessness (three point scale), temperature symptoms (two point scale), and presence of hypertension (yes or no); the area under the curve was 0·80 (95% CI 0·76-0·85) and on validation the negative predictive value of a low risk designation was 99% (95% CI 98·1-99·2; 1435 of 1453). RECAP-O2 included age (years), degree of breathlessness (two point scale), fatigue (two point scale), and SpO at rest (as a percentage); the area under the curve was 0·84 (0·78-0·90) and on validation the negative predictive value of low risk designation was 99% (95% CI 98·9-99·7; 1176 of 1183). Both RECAP models are valid tools to assess COVID-19 patients in the community. RECAP-GP can be used initially, without need for observations, to identify patients who require monitoring. If the patient is monitored and SpO is available, RECAP-O2 is useful to assess the need for treatment escalation. Community Jameel and the Imperial College President's Excellence Fund, the Economic and Social Research Council, UK Research and Innovation, and Health Data Research UK.

Influenza is a major public health burden, mainly prevented by vaccination. Recommendations on influenza vaccine composition are updated annually and constant benefit-risk monitoring is therefore needed. We conducted near-real-time enhanced passive surveillance (EPS) for the influenza vaccine, Fluarix Tetra, according to European Medicines Agency guidance, in 10 volunteer general practices in England using Fluarix Tetra as their principal influenza vaccine brand, from 1-Sep to 30-Nov-2016. The EPS method used a combination of routinely collected data from electronic health records (EHR) and a customized adverse events reporting card (AERC) distributed to participants vaccinated with Fluarix Tetra. For participants vaccinated with a different influenza vaccine, data were derived exclusively from the EHR. We reported weekly and cumulative incidence of pre-defined adverse events of interest (AEI) occurring within 7 days post-vaccination, adjusted for clustering effect. Of the 97,754 eligible participants, 19,334 (19.8%) received influenza vaccination, of whom 13,861 (71.7%) received Fluarix Tetra. A total of 1,049 participants receiving Fluarix Tetra reported AEIs; 703 (67%) used the AERC (adjusted cumulative incidence rate 4.96% [95% CI: 3.92−6.25]). Analysis by individual pre-specified AEI categories identified no safety signal for Fluarix Tetra. A total of 62 individuals reported an AEI with a known brand of non-GSK influenza vaccine and 54 with an unknown brand (adjusted cumulative incidence rate 2.59% [1.93−3.47] and 1.77% [1.42−2.20], respectively). In conclusion, the study identified no safety signal for Fluarix Tetra and showed that the AERC was a useful tool that complemented routine pharmacovigilance by allowing more comprehensive capture of AEIs.

•Overall, booster uptake was at 91% by 29th February 2022.•Uptake lower in more deprived areas and the Black ethnic group.•Booster uptake comparable to first dose under primary schedule.•Booster infection breakthrough most likely for those living with children.•Booster breakthrough comparable to second dose under primary schedule. From September 2021, Health Care Workers (HCWs) in Wales began receiving a COVID-19 booster vaccination. This is the first dose beyond the primary vaccination schedule. Given the emergence of new variants, vaccine waning vaccine, and increasing vaccination hesitancy, there is a need to understand booster vaccine uptake and subsequent breakthrough in this high-risk population. We conducted a prospective, national-scale, observational cohort study of HCWs in Wales using anonymised, linked data from the SAIL Databank. We analysed uptake of COVID-19 booster vaccinations from September 2021 to February 2022, with comparisons against uptake of the initial primary vaccination schedule. We also analysed booster breakthrough, in the form of PCR-confirmed SARS-Cov-2 infection, comparing to the second primary dose. Cox proportional hazard models were used to estimate associations for vaccination uptake and breakthrough regarding staff roles, socio-demographics, household composition, and other factors. We derived a cohort of 73,030 HCWs living in Wales (78% female, 60% 18–49 years old). Uptake was quickest amongst HCWs aged 60 + years old (aHR 2.54, 95%CI 2.45–2.63), compared with those aged 18–29. Asian HCWs had quicker uptake (aHR 1.18, 95%CI 1.14–1.22), whilst Black HCWs had slower uptake (aHR 0.67, 95%CI 0.61–0.74), compared to white HCWs. HCWs residing in the least deprived areas were slightly quicker to have received a booster dose (aHR 1.12, 95%CI 1.09–1.16), compared with those in the most deprived areas. Strongest associations with breakthrough infections were found for those living with children (aHR 1.52, 95%CI 1.41–1.63), compared to two-adult only households. HCWs aged 60 + years old were less likely to get breakthrough infections, compared to those aged 18–29 (aHR 0.42, 95%CI 0.38–0.47). Vaccination uptake was consistently lower among black HCWs, as well as those from deprived areas. Whilst breakthrough infections were highest in households with children.

INTRODUCTION: Routinely collected primary care data has underpinned research that has helped define primary care as a specialty. In the early years of the discipline, data were collected manually, but digital data collection now makes large volumes of data readily available. Primary care informatics is emerging as an academic discipline for the scientific study of how to harness these data. This paper reviews how data are stored in primary care computer systems; current use of large primary care research databases; and, the opportunities and challenges for using routinely collected primary care data in research. OPPORTUNITIES: (1) Growing volumes of routinely recorded data. (2) Improving data quality. (3) Technological progress enabling large datasets to be processed. (4) The potential to link clinical data in family practice with other data including genetic databases. (5) An established body of know-how within the international health informatics community. CHALLENGES: (1) Research methods for working with large primary care datasets are limited. (2) How to infer meaning from data. (3) Pace of change in medicine and technology. (4) Integrating systems where there is often no reliable unique identifier and between health (person-based records) and social care (care-based records-e.g. child protection). (5) Achieving appropriate levels of information security, confidentiality, and privacy. CONCLUSION: Routinely collected primary care computer data, aggregated into large databases, is used for audit, quality improvement, health service planning, epidemiological study and research. However, gaps exist in the literature about how to find relevant data, select appropriate research methods and ensure that the correct inferences are drawn.

There is a need for better understanding of the risk of thrombocytopenic, haemorrhagic, thromboembolic disorders following first, second and booster vaccination doses and testing positive for SARS-CoV-2. Self-controlled cases series analysis of 2.1 million linked patient records in Wales between 7th December 2020 and 31st December 2021. Outcomes were the first diagnosis of thrombocytopenic, haemorrhagic and thromboembolic events in primary or secondary care datasets, exposure was defined as 0-28 days post-vaccination or a positive reverse transcription polymerase chain reaction test for SARS-CoV-2. 36,136 individuals experienced either a thrombocytopenic, haemorrhagic or thromboembolic event during the study period. Relative to baseline, our observations show greater risk of outcomes in the periods post-first dose of BNT162b2 for haemorrhagic (IRR 1.47, 95%CI: 1.04-2.08) and idiopathic thrombocytopenic purpura (IRR 2.80, 95%CI: 1.21-6.49) events; post-second dose of ChAdOx1 for arterial thrombosis (IRR 1.14, 95%CI: 1.01-1.29); post-booster greater risk of venous thromboembolic (VTE) (IRR-Moderna 3.62, 95%CI: 0.99-13.17) (IRR-BNT162b2 1.39, 95%CI: 1.04-1.87) and arterial thrombosis (IRR-Moderna 3.14, 95%CI: 1.14-8.64) (IRR-BNT162b2 1.34, 95%CI: 1.15-1.58). Similarly, post SARS-CoV-2 infection the risk was increased for haemorrhagic (IRR 1.49, 95%CI: 1.15-1.92), VTE (IRR 5.63, 95%CI: 4.91, 6.4), arterial thrombosis (IRR 2.46, 95%CI: 2.22-2.71). We found that there was a measurable risk of thrombocytopenic, haemorrhagic, thromboembolic events after COVID-19 vaccination and infection.

Background: During the pandemic, remote consultations have become the norm for assessing patients with signs and symptoms of COVID-19 to decrease the risk of transmission. This has intensified the clinical uncertainty already experienced by primary care clinicians when assessing patients with suspected COVID-19 and has prompted the use of risk prediction scores, such as the National Early Warning Score (NEWS2), to assess severity and guide treatment. However, the risk prediction tools available have not been validated in a community setting and are not designed to capture the idiosyncrasies of COVID-19 infection. Objective: The objective of this study is to produce a multivariate risk prediction tool, RECAP-V1 (Remote COVID-19 Assessment in Primary Care), to support primary care clinicians in the identification of those patients with COVID-19 that are at higher risk of deterioration and facilitate the early escalation of their treatment with the aim of improving patient outcomes. Methods: The study follows a prospective cohort observational design, whereby patients presenting in primary care with signs and symptoms suggestive of COVID-19 will be followed and their data linked to hospital outcomes (hospital admission and death). Data collection will be carried out by primary care clinicians in four arms: North West London Clinical Commissioning Groups (NWL CCGs), Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC), Covid Clinical Assessment Service (CCAS), and South East London CCGs (Doctaly platform). The study involves the use of an electronic template that incorporates a list of items (known as RECAP-V0) thought to be associated with disease outcome according to previous qualitative work. Data collected will be linked to patient outcomes in highly secure environments. We will then use multivariate logistic regression analyses for model development and validation. Results: Recruitment of participants started in October 2020. Initially, only the NWL CCGs and RCGP RSC arms were active. As of March 24, 2021, we have recruited a combined sample of 3827 participants in these two arms. CCAS and Doctaly joined the study in February 2021, with CCAS starting the recruitment process on March 15, 2021. The first part of the analysis (RECAP-V1 model development) is planned to start in April 2021 using the first half of the NWL CCGs and RCGP RSC combined data set. Posteriorly, the model will be validated with the rest of the NWL CCGs and RCGP RSC data as well as the CCAS and Doctaly data sets. The study was approved by the Research Ethics Committee on May 27, 2020 (Integrated Research Application System number: 283024, Research Ethics Committee reference number: 20/NW/0266) and badged as National Institute of Health Research Urgent Public Health Study on October 14, 2020. Conclusions: We believe the validated RECAP-V1 early warning score will be a valuable tool for the assessment of severity in patients with suspected COVID-19 in the community, either in face-to-face or remote consultations, and will facilitate the timely escalation of treatment with the potential to improve patient outcomes.

A previous efficacy trial found benefit from inhaled budesonide for COVID-19 in patients not admitted to hospital, but effectiveness in high-risk individuals is unknown. We aimed to establish whether inhaled budesonide reduces time to recovery and COVID-19-related hospital admissions or deaths among people at high risk of complications in the community. PRINCIPLE is a multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial done remotely from a central trial site and at primary care centres in the UK. Eligible participants were aged 65 years or older or 50 years or older with comorbidities, and unwell for up to 14 days with suspected COVID-19 but not admitted to hospital. Participants were randomly assigned to usual care, usual care plus inhaled budesonide (800 μg twice daily for 14 days), or usual care plus other interventions, and followed up for 28 days. Participants were aware of group assignment. The coprimary endpoints are time to first self-reported recovery and hospital admission or death related to COVID-19, within 28 days, analysed using Bayesian models. The primary analysis population included all eligible SARS-CoV-2-positive participants randomly assigned to budesonide, usual care, and other interventions, from the start of the platform trial until the budesonide group was closed. This trial is registered at the ISRCTN registry (ISRCTN86534580) and is ongoing. The trial began enrolment on April 2, 2020, with randomisation to budesonide from Nov 27, 2020, until March 31, 2021, when the prespecified time to recovery superiority criterion was met. 4700 participants were randomly assigned to budesonide (n=1073), usual care alone (n=1988), or other treatments (n=1639). The primary analysis model includes 2530 SARS-CoV-2-positive participants, with 787 in the budesonide group, 1069 in the usual care group, and 974 receiving other treatments. There was a benefit in time to first self-reported recovery of an estimated 2·94 days (95% Bayesian credible interval [BCI] 1·19 to 5·12) in the budesonide group versus the usual care group (11·8 days [95% BCI 10·0 to 14·1] vs 14·7 days [12·3 to 18·0]; hazard ratio 1·21 [95% BCI 1·08 to 1·36]), with a probability of superiority greater than 0·999, meeting the prespecified superiority threshold of 0·99. For the hospital admission or death outcome, the estimated rate was 6·8% (95% BCI 4·1 to 10·2) in the budesonide group versus 8·8% (5·5 to 12·7) in the usual care group (estimated absolute difference 2·0% [95% BCI -0·2 to 4·5]; odds ratio 0·75 [95% BCI 0·55 to 1·03]), with a probability of superiority 0·963, below the prespecified superiority threshold of 0·975. Two participants in the budesonide group and four in the usual care group had serious adverse events (hospital admissions unrelated to COVID-19). Inhaled budesonide improves time to recovery, with a chance of also reducing hospital admissions or deaths (although our results did not meet the superiority threshold), in people with COVID-19 in the community who are at higher risk of complications. National Institute of Health Research and United Kingdom Research Innovation.

Background: The Patient Assessment of Care for Chronic Conditions (PACIC-5As) is a questionnaire developed in English and designed to evaluate the health care experiences of people living with chronic conditions such as diabetes. Aims: This study aimed to translate, culturally adapt and validate the PACIC-5As instrument for the Arab context in a sample of Saudi Arabian people with diabetes. Methods: The PACIC-5As was translated into Arabic using a forward and backward translation process. The Arabic version was then validated with a sample of 557 Saudi Arabians with diabetes who were recruited from tertiary level diabetes centres in Riyadh between January and March 2018. In order to evaluate the psychometric properties of the Arabic version, Cronbach alphas and item correlations were determined and exploratory factor analysis was performed. Results: The translated PACIC-5As had good psychometric quality. Cronbach alpha was > 0.9 and the inter-item correlation ranged between 0.36 and 0.56. Exploratory factor analysis showed a single-factor structure. Conclusion: An Arabic version of the PACIC-5As questionnaire is now available to assess the experience of patients with diabetes. The results of this study can be used to improve the quality of the delivery of health care in Arabic-speaking countries.

It is unclear to what extent the findings of the sodium–glucose co‐transporter‐2 (SGLT‐2) inhibitor cardiovascular outcomes trials (CVOTs) are generalizable to the real‐world type 2 diabetes populations. Using a national primary care database, we found that the inclusion criteria of four SGLT‐2 inhibitor CVOTs applied to between 7% and 27% of people with type 2 diabetes. Generalizability of the findings from CVOTs to a wider type 2 diabetes population may be restricted to groups defined by the inclusion criteria for each trial. Uniform inclusion criteria for trials would allow direct comparison to be made between trials.

The mechanisms underlying the adverse cardiovascular effects of increased salt intake are incompletely understood, but parallel increases in serum sodium concentration may be of importance. The aim of this retrospective cohort study was to investigate the relationship between serum sodium, hypertension and incident cardiovascular disease (CVD). Routinely collected primary care data from the Royal College of General Practitioners Research and Surveillance Centre were analysed. A total of 231,545 individuals with a measurement of serum sodium concentration at baseline were included. Exclusion criteria were: age < 40 years; abnormal serum sodium; diabetes mellitus; prior CVD event; stage 5 chronic kidney disease; and liver cirrhosis. The primary outcome was incident CVD (myocardial infarction, acute coronary syndrome, coronary revascularisation, stroke, transient ischaemic attack or new heart failure diagnosis) over 5 years. There was a 'J-shaped' relationship between serum sodium concentration and primary cardiovascular events that was independent of established risk factors, medications and other serum electrolytes. The lowest cardiovascular risk was found with a serum sodium between 141 and 143 mmol/l. Higher serum sodium was associated with increased risk in hypertensive individuals, whereas lower concentrations were associated with increased risk in all individuals. Therefore, alterations in serum sodium concentration may be a useful indicator of CVD risk. Higher serum sodium could have a direct effect on the vasculature, particularly in hypertensive individuals. Lower serum sodium may be a reflection of complex volume and neuroendocrine changes.

Aim To investigate the impact of glycaemic control on infection incidence in people with Type 2 diabetes. Methods We compared infection rates during 2014 in people with Type 2 diabetes and people without diabetes in a large primary care cohort in the UK (the Royal College of General Practitioners Research and Surveillance Centre database). We performed multilevel logistic regression to investigate the impact of Type 2 diabetes on presentation with infection, and the effect of glycaemic control on presentation with upper respiratory tract infections, bronchitis, influenza-like illness, pneumonia, intestinal infectious diseases, herpes simplex, skin and soft tissue infections, urinary tract infections, and genital and perineal infections. People with Type 2 diabetes were stratified by good [HbA1c < 53 mmol/mol (< 7%)], moderate [HbA1c 53–69 mmol/mol (7–8.5%)] and poor [HbA1c > 69 mmol/mol (> 8.5%)] glycaemic control using their most recent HbA1c concentration. Infection incidence was adjusted for important sociodemographic factors and patient comorbidities. Results We identified 34 278 people with Type 2 diabetes and 613 052 people without diabetes for comparison. The incidence of infections was higher in people with Type 2 diabetes for all infections except herpes simplex. Worsening glycaemic control was associated with increased incidence of bronchitis, pneumonia, skin and soft tissue infections, urinary tract infections, and genital and perineal infections, but not with upper respiratory tract infections, influenza-like illness, intestinal infectious diseases or herpes simplex. Conclusions Almost all infections analysed were more common in people with Type 2 diabetes. Infections that are most commonly of bacterial, fungal or yeast origin were more frequent in people with worse glycaemic control.

Most chronic diseases are managed in primary and ambulatory care. The chronic care model (CCM) suggests a wide range of community, technological, team and patient factors contribute to effective chronic disease management. Ontologies have the capability to enable formalised linkage of heterogeneous data sources as might be found across the elements of the CCM.

Hypertension has been identified as a risk factor for coronavirus disease 2019 (COVID-19) and associated adverse outcomes. This study examined the association between preinfection blood pressure (BP) control and COVID-19 outcomes using data from 460 general practices in England. Eligible patients were adults with hypertension who were tested or diagnosed with COVID-19. BP control was defined by the most recent BP reading within 24 months of the index date (January 1, 2020). BP was defined as controlled (

Objective To assess the association between anticoagulation, ischaemic stroke, gastrointestinal and cerebral haemorrhage, and all cause mortality in older people with atrial fibrillation and chronic kidney disease. Design Propensity matched, population based, retrospective cohort analysis from January 2006 through December 2016. Setting The Royal College of General Practitioners Research and Surveillance Centre database population of almost 2.73 million patients from 110 general practices across England and Wales. Participants Patients aged 65 years and over with a new diagnosis of atrial fibrillation and estimated glomerular filtration rate (eGFR) of

Introduction Total population mortality rates have been falling and life expectancy increasing for more than 30 years. Diabetes remains a significant risk factor for premature death. Here we used the Oxford Royal College of General Practitioners Research and Surveillance Centre (RCGP RSC) practices to determine diabetes-related vs non-diabetes-related mortality rates. Methods RCGP RSC data were provided on annual patient numbers and deaths, at practice level, for those with and without diabetes across four age groups (< 50, 50-64, 65-79, >= 80 years) over 15 years. Investment in diabetes control, as measured by the cost of primary care medication, was also taken from GP prescribing data. Results We included 527 general practices. Over the period 2004-2019, there was no significant change in life years lost, which varied between 4.6 and 5.1 years over this period. The proportion of all diabetes deaths by age band was significantly higher in the 65-79 years age group for men and women with diabetes than for their non-diabetic counterparts. For the year 2019, 26.6% of deaths were of people with diabetes. Of this 26.6%, 18.5% would be expected from age group and non-diabetes status, while the other 8.1% would not have been expected-pro rata to nation, this approximates to approximately 40,000 excess deaths in people with diabetes vs the general population. Conclusion There remains a wide variation in mortality rate of people with diabetes between general practices in UK. The mortality rate and life years lost for people with diabetes vs non-diabetes individuals have remained stable in recent years, while mortality rates for the general population have fallen. Investment in diabetes management at a local and national level is enabling us to hold the ground regarding the life-shortening consequences of having diabetes as increasing numbers of people develop T2DM at a younger age.

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 5middot4 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, 2572008 individuals received their first dose of vaccine-841 090 (32middot7%) received BNT162b2 and 1 730 918 (67middot3%) received ChAdOx1. 1196 (= 80 years vs 18-64 years adjusted RR 4middot75, 95% CI 3middot85-5middot87), comorbidities (five or more risk groups vs less than five risk groups 4middot24, 3middot34-5middot39), hospitalisation in the previous 4 weeks (3middot00, 2middot47-3middot65), high-risk occupations (ten or more previous COVID-19 tests vs less than ten previous COVID-19 tests 2middot14, 1middot62-2middot81), care home residence (1middot63, 1middot32-2middot02), socioeconomic deprivation (most deprived quintile vs least deprived quintile 1middot57, 1middot30-1middot90), being male (1middot27, 1middot13-1middot43), and being an ex-smoker (ex-smoker vs non-smoker 1middot18, 1middot01-1middot38). A history of COVID-19 before vaccination was protective (0middot40, 0middot29-0middot54). 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.

Objectives: To compare the contribution of physician associates to the processes and outcomes of emergency medicine consultations with that of foundation year two doctors-in-training. Design: Mixed-methods study: retrospective chart review using 4 months’ anonymised clinical record data of all patients seen by physician associates or foundation year two doctors-in-training in 2016; review of a subsample of 40 records for clinical adequacy; semi-structured interviews with staff and patients; observations of physician associates. Setting: Three emergency departments in England. Participants: The records of 8816 patients attended by 6 physician associates and 40 foundation year two doctors-in-training; of these n=3197 had the primary outcome recorded (n=1129 physician associates, n=2068 doctor); 14 clinicians and managers and 6 patients or relatives for interview; 5 physician associates for observation. Primary and secondary outcome measures: The primary outcome was unplanned re-attendance at the same emergency department within 7 days. Secondary outcomes: consultation processes, clinical adequacy of care, and staff and patient experience. Results: Re-attendances within 7 days (n=194 (6.1%)) showed no difference between physician associates and foundation year two doctors-in-training (OR 0.87, 95% CI 0.61 to 1.24, p=0.437). If seen by a physician associate, patients were more likely receive an X-ray investigation (OR 2.10, 95% CI 1.72 to 4.24), p

OBJECTIVE: This study was conducted to describe the incidence of diabetes following pancreatic disease, assess how these patients are classified by clinicians, and compare clinical characteristics with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: Primary care records in England (n = 2,360,631) were searched for incident cases of adult-onset diabetes between 1 January 2005 and 31 March 2016. We examined demographics, diabetes classification, glycemic control, and insulin use in those with and without pancreatic disease (subcategorized into acute pancreatitis or chronic pancreatic disease) before diabetes diagnosis. Regression analysis was used to control for baseline potential risk factors for poor glycemic control (HbA1c ≥7% [53 mmol/mol]) and insulin requirement. RESULTS: We identified 31,789 new diagnoses of adult-onset diabetes. Diabetes following pancreatic disease (2.59 [95% CI 2.38–2.81] per 100,000 person-years) was more common than type 1 diabetes (1.64 [1.47–1.82]; P < 0.001). The 559 cases of diabetes following pancreatic disease were mostly classified by clinicians as type 2 diabetes (87.8%) and uncommonly as diabetes of the exocrine pancreas (2.7%). Diabetes following pancreatic disease was diagnosed at a median age of 59 years and BMI of 29.2 kg/m2. Diabetes following pancreatic disease was associated with poor glycemic control (adjusted odds ratio, 1.7 [1.3–2.2]; P < 0.001) compared with type 2 diabetes. Insulin use within 5 years was 4.1% (3.8–4.4) with type 2 diabetes, 20.9% (14.6–28.9) with diabetes following acute pancreatitis, and 45.8% (34.2–57.9) with diabetes following chronic pancreatic disease. CONCLUSIONS: Diabetes of the exocrine pancreas is frequently labeled type 2 diabetes but has worse glycemic control and a markedly greater requirement for insulin.

Near-real time feedback on data quality allows clinicians and data managers at general practices to collectively contribute to improving the reliability of observational data. We report features of an enhanced dashboard used for virological surveillance after the first season of utilisation. Time-series analysis performed on dashboard usage data from 68 general practices (denominator = 722,409) indicated utilisation patterns that correlated to influenza vaccination in general practices. Near real time feedback via a dashboard may improve data quality and possibly vaccine uptake.

Background: Primary health care is changing as it responds to demographic shifts, technological changes and fiscal constraints. This, and predicted pressures on medical and nursing workforces, raises questions about staffing configurations. Physician assistants (PAs) are mid-level practitioners, trained in a medical model over 2 years at postgraduate level to work under a supervising doctor. A small number of general practices in England have employed PAs. Objective: To investigate the contribution of PAs to the delivery of patient care in primary care services in England. Design: A mixed-methods study conducted at macro, meso and micro organisational levels in two phases: (1) a rapid review, a scoping survey of key national and regional informants, a policy review, and a survey of PAs and (2) comparative case studies in 12 general practices (six employing PAs). The latter incorporated clinical record reviews, a patient satisfaction survey, video observations of consultations and interviews with patients and professionals. Results: The rapid review found 49 published studies, mainly from the USA, which showed increased numbers of PAs in general practice settings but weak evidence for impact on processes and patient outcomes. The scoping survey found mainly positive or neutral views about PAs, but there was no mention of their role in workforce policy and planning documents. The survey of PAs in primary care (n = 16) found that they were mainly deployed to provide same-day appointments. The comparative case studies found that physician assistants were consulted by a wide range of patients, but these patients tended to be younger, with less medically acute or complex problems than those consulting general practitioners (GPs). Patients reported high levels of satisfaction with both PAs and GPs. The majority were willing or very willing to consult a PA again but wanted choice in which type of professional they consulted. There was no significant difference between PAs and GPs in the primary outcome of patient reconsultation for the same problem within 2 weeks, investigations/tests ordered, referrals to secondary care or prescriptions issued. GPs, blinded to the type of clinician, judged the documented activities in the initial consultation of patients who reconsulted for the same problem to be appropriate in 80% (n = 223) PA and 50% (n = 252) GP records. PAs were judged to be competent and safe from observed consultations. The average consultation with a physician assistant is significantly longer than that with a GP: 5.8 minutes for patients of average age for this sample (38 years). Costs per consultation were £34.36 for GPs and £28.14 for PAs. Costs could not be apportioned to GPs for interruptions, supervision or training of PAs.Conclusions: PAs were found to be acceptable, effective and efficient in complementing the work of GPs. PAs can provide a flexible addition to the primary care workforce. They offer another labour pool to consider in health professional workforce and education planning at local, regional and national levels. However, in order to maximise the contribution of PAs in primary care settings, consideration needs to be given to the appropriate level of regulation and the potential for authority to prescribe medicines. Future research is required to investigate the contribution of PAs to other first contact services as well as secondary services; the contribution and impact of all types of mid-level practitioners (including nurse practitioners) in first contact services; the factors and influences on general practitioner and practice manager decision-making as to staffing and skill mix; and the reliability and validity of classification systems for both primary care patients and their presenting condition and their consequences for health resource utilisation.

Background Ethnicity recording within primary care computerised medical record (CMR) systems is suboptimal, exacerbated by tangled taxonomies within current coding systems. Objective To develop a method for extending ethnicity identification using routinely collected data. Methods We used an ontological method to maximise the reliability and prevalence of ethnicity information in the Royal College of General Practitioner’s Research and Surveillance database. Clinical codes were either directly mapped to ethnicity group or utilised as proxy markers (such as language spoken) from which ethnicity could be inferred. We compared the performance of our method with the recording rates that would be identified by code lists utilised by the UK pay for the performance system, with the help of the Quality and Outcomes Framework (QOF). Results Data from 2,059,453 patients across 110 practices were included. The overall categorisable ethnicity using QOF codes was 36.26% (95% confidence interval (CI): 36.20%–36.33%). This rose to 48.57% (CI:48.50%–48.64%) using the described ethnicity mapping process. Mapping increased across all ethnic groups. The largest increase was seen in the white ethnicity category (30.61%; CI: 30.55%–30.67% to 40.24%; CI: 40.17%–40.30%). The highest relative increase was in the ethnic group categorised as the other (0.04%; CI: 0.03%–0.04% to 0.92%; CI: 0.91%–0.93%). Conclusions This mapping method substantially increases the prevalence of known ethnicity in CMR data and may aid future epidemiological research based on routine data.

Introduction Worldwide, pancreatic cancer has a poor prognosis. Early diagnosis may improve survival by enabling curative treatment. Statistical and machine learning diagnostic prediction models using risk factors such as patient demographics and blood tests are being developed for clinical use to improve early diagnosis. One example is the Enriching New-onset Diabetes for Pancreatic Cancer (ENDPAC) model, which employs patients’ age, blood glucose and weight changes to provide pancreatic cancer risk scores. These values are routinely collected in primary care in the UK. Primary care’s central role in cancer diagnosis makes it an ideal setting to implement ENDPAC but it has yet to be used in clinical settings. This study aims to determine the feasibility of applying ENDPAC to data held by UK primary care practices. Methods and analysis This will be a multicentre observational study with a cohort design, determining the feasibility of applying ENDPAC in UK primary care. We will develop software to search, extract and process anonymised data from 20 primary care providers’ electronic patient record management systems on participants aged 50+ years, with a glycated haemoglobin (HbA1c) test result of ≥48 mmol/mol (6.5%) and no previous abnormal HbA1c results. Software to calculate ENDPAC scores will be developed, and descriptive statistics used to summarise the cohort’s demographics and assess data quality. Findings will inform the development of a future UK clinical trial to test ENDPAC’s effectiveness for the early detection of pancreatic cancer. Ethics and dissemination This project has been reviewed by the University of Surrey University Ethics Committee and received a favourable ethical opinion (FHMS 22-23151 EGA). Study findings will be presented at scientific meetings and published in international peer-reviewed journals. Participating primary care practices, clinical leads and policy makers will be provided with summaries of the findings.

Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type 2 diabetes, cardiovascular disease and related metabolic and inflammatory disturbances1,2. Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation3,4,5,6, a key regulator of gene expression and molecular phenotype7. Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P 

To identify risk factors for falls and generate two screening tools: an opportunistic tool for use in consultation to flag at risk patients and a systematic database screening tool for comprehensive falls assessment of the practice population.

At the end of 2020, many countries commenced a vaccination programme against SARS-CoV-2. Public health authorities aim to prevent and interrupt outbreaks of infectious disease in social care settings. We aimed to investigate the association between the introduction of the vaccination programme and the frequency and duration of COVID-19 outbreaks in Northern Ireland (NI). We undertook an ecological study using routinely available national data. We used Poisson regression to measure the relationship between the number of RT-PCR confirmed COVID-19 outbreaks in care homes, and as a measure of community COVID-19 prevalence, the Office for National Statistics COVID-19 Infection Survey estimated the number of people testing positive for COVID-19 in NI. We estimated the change in this relationship and estimated the expected number of care home outbreaks in the absence of the vaccination programme. A Cox proportional hazards model estimated the hazard ratio of a confirmed COVID-19 care home outbreak closure. Care home outbreaks reduced by two-thirds compared to expected following the introduction of the vaccination programme, from a projected 1625 COVID-19 outbreaks (95% prediction interval 1553–1694) between 7 December 2020 and 28 October 2021 to an observed 501. We estimated an adjusted hazard ratio of 2.53 of the outbreak closure assuming a 21-day lag for immunity. These findings describe the association of the vaccination with a reduction in outbreak frequency and duration across NI care homes. This indicates probable reduced harm and disruption from COVID-19 in social care settings following vaccination. Future research using individual level data from care home residents will be needed to investigate the effectiveness of the vaccines and the duration of their effects.

INTRODUCTION: Increasing investment in eHealth aims to improve cost effectiveness and safety of care. Data extraction and aggregation can create new data products to improve professional practice and provide feedback to improve the quality of source data. A previous systematic review concluded that locally relevant clinical indicators and use of clinical record systems could support clinical governance. We aimed to extend and update the review with a theoretical framework. METHODS: We searched PubMed, Medline, Web of Science, ABI Inform (Proquest) and Business Source Premier (EBSCO) using the terms curation, information ecosystem, data quality management (DQM), data governance, information governance (IG) and data stewardship. We focused on and analysed the scope of DQM and IG processes, theoretical frameworks, and determinants of the processing, quality assurance, presentation and sharing of data across the enterprise. FINDINGS: There are good theoretical reasons for integrated governance, but there is variable alignment of DQM, IG and health system objectives across the health enterprise. Ethical constraints exist that require health information ecosystems to process data in ways that are aligned with improving health and system efficiency and ensuring patient safety. Despite an increasingly 'big-data' environment, DQM and IG in health services are still fragmented across the data production cycle. We extend current work on DQM and IG with a theoretical framework for integrated IG across the data cycle. CONCLUSIONS: The dimensions of this theory-based framework would require testing with qualitative and quantitative studies to examine the applicability and utility, along with an evaluation of its impact on data quality across the health enterprise.

Background Rapidly undertaken age-stratified serology studies can produce valuable data about a new emerging infection including background population immunity and seroincidence during an influenza pandemic. Traditionally seroepidemiology studies have used surplus laboratory sera with little or no clinical information or have been expensive detailed population based studies. We propose collecting population based sera from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC), a sentinel network with extensive clinical data. Aim To pilot a mechanism to undertake population based surveys that collect serological specimens and associated patient data to measure seropositivity and seroincidence due to seasonal influenza, and create a population based serology bank. Methods and analysis Setting and Participants: We will recruit 6 RCGP RSC practices already taking nasopharyngeal virology swabs. Patients who attend a scheduled blood test will be consented to donate additional blood samples. Approximately 100-150 blood samples will be collected from each of the following age bands -18-29, 30-39, 40-49, 50-59, 60-69 and 70+ years. Methods We will send the samples to the Public Health England (PHE) Seroepidemiology Unit for processing and storage. These samples will be tested for influenza antibodies, using haemagglutination inhibition assays. Serology results will be pseudonymised, sent to the RCGP RSC and combined using existing processes at the RCGP RSC secure hub. The influenza seroprevalence results from the RCGP cohort will be compared against those from the annual PHE influenza residual serosurvey. Ethics and dissemination Ethical approval was granted by the Proportionate Review Sub-Committee of the London - Camden & Kings Cross on 6 February 2018. This study received approval from Health Research Authority on 7 February 2018. On completion the results will be made available via peer-reviewed journals.

BackgroundData processing of health research databases often requires a Data Protection Impact Assessment to evaluate the severity of the risk and the appropriateness of measures taken to comply with the European Union (EU) General Data Protection Regulation (GDPR). We aimed to define and apply a comprehensive method for the evaluation of privacy, data governance and ethics among research networks involved in the EU Project Bridge Health.MethodsComputerised survey among associated partners of main EU Consortia, using a targeted instrument designed by the principal investigator and progressively refined in collaboration with an international advisory panel. Descriptive measures using the percentage of adoption of privacy, data governance and ethical principles as main endpoints were used for the analysis and interpretation of the results.ResultsA total of 15 centres provided relevant information on the processing of sensitive data from 10 European countries. Major areas of concern were noted for: data linkage (median, range of adoption: 45%, 30%–80%), access and accuracy of personal data (50%, 0%–100%) and anonymisation procedures (56%, 11%–100%). A high variability was noted in the application of privacy principles.ConclusionsA comprehensive methodology of Privacy and Ethics Impact and Performance Assessment was successfully applied at international level. The method can help implementing the GDPR and expanding the scope of Data Protection Impact Assessment, so that the public benefit of the secondary use of health data could be well balanced with the respect of personal privacy.

Introduction: The chronic care model (CCM) provides a holistic approach for managing chronic illnesses. Patients with rare liver diseases (RLD) have complex needs, impaired quality of life and often life-threatening complications. Most RLD meet the criteria for a long-term chronic condition and should be viewed through the prism of CCM. We aimed to ascertain whether the CCM has been considered for the frequently-encountered RLD. Methods: MEDLINE®/PubMed®/Cochrane/EMBASE were searched to identify publications relating to the use of the CCM for the management of six RLD. We identified 33 articles eligible for inclusion. Results: Six, eleven, one, thirteen, two and zero studies, discussed individual components of the CCM for autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cirrhosis (PSC), Wilsons disease (WD), alpha-1 antitrypsin deficiency (A1AD) and lysosomal acid lipase deficiency (LALd) respectively. We have not identified studies using the full CCM for any of the aforementioned RLD. Discussion: Unlike in common chronic conditions e.g. diabetes, there has been limited consideration of the use of CCM (or its components) for the management of RLD. This may reflect a reluctance of the clinical community to view these diseases as chronic or lack of healthcare policy investment in rare diseases in general.

Aims To determine obstructive sleep apnoea prevalence in people with Type 2 or Type 1 diabetes in a national primary care setting, stratified by BMI category, and to explore the relationship between patient characteristics and obstructive sleep apnoea. Methods Using the Royal College of General Practitioners Research and Surveillance Centre database, a cross-sectional analysis was conducted. Diabetes type was identified using a seven-step algorithm and was grouped by Type 2 diabetes, Type 1 diabetes and no diabetes. The clinical characteristics of these groups were analysed, BMI-stratified obstructive sleep apnoea prevalence rates were calculated, and a multilevel logistic regression analysis was completed on the Type 2 diabetes group. Results Analysis of 1 275 461 adult records in the Royal College of General Practitioners Research and Surveillance Centre network showed that obstructive sleep apnoea was prevalent in 0.7%. In people with Type 2 diabetes, obstructive sleep apnoea prevalence increased with each increasing BMI category, from 0.5% in those of normal weight to 9.6% in those in the highest obesity class. By comparison, obstructive sleep apnoea prevalence rates for these BMI categories in Type 1 diabetes were 0.3% and 4.3%, and in those without diabetes 1.2% and 3.9%, respectively. Obstructive sleep apnoea was more prevalent in men than women in both diabetes types. When known risk factors were adjusted for, there were increased odds ratios for obstructive sleep apnoea in people with Type 2 diabetes in the overweight and higher BMI categories. Conclusions Obstructive sleep apnoea was reported in people with both types of diabetes across the range of overweight categories and not simply in the highest obesity class.

Background: In England, most prescribing of direct-acting oral anticoagulants for atrial fibrillation (AF) is in primary care. However, there remain gaps in our understanding of dosage and disparities in use. We aimed to describe trends in direct oral anticoagulant (DOAC) prescribing, including dose reduction in people with renal impairment and other criteria, and adherence. Methods: Using English primary care sentinel network data from 2014 to 2019, we assessed appropriate DOAC dose adjustment with creatinine clearance (CrCl). Our primary care sentinel cohort was a subset of 722 general practices, with 6.46 million currently registered patients at the time of this study. Results: Of 6 464 129 people in the cohort, 2.3% were aged ≥18 years with a diagnosis of AF, and 30.8% of these were prescribed vitamin K antagonist and 69.1% DOACs. Appropriate DOAC prescribing following CrCl measures improved between 2014 and 2019; dabigatran from 21.3% (95% CI 15.1% to 28.8%) to 48.7% (95% CI 45.0% to 52.4%); rivaroxaban from 22.1% (95% CI 16.7% to 28.4%) to 49.9% (95% CI 48.5% to 53.3%); edoxaban from 10.0% (95% CI 0.3% to 44.5%) in 2016 to 57.6% (95% CI 54.5% to 60.7%) in 2019; apixaban from 30.8% (95% CI 9.1% to 61.4%) in 2015 to 60.5% (95% CI 57.8% to 63.2%) in 2019. Adherence was highest for factor Xa inhibitors, increasing from 50.1% (95% CI 47.7% to 52.4%) in 2014 to 57.8% (95% CI 57.4% to 58.2%) in 2019. Asian and black/mixed ethnicity was associated with non-adherence (OR 1.81, 95% CI 1.56 to 2.09) as was male gender (OR 1.19, 95% CI 1.15 to 1.22), higher socioeconomic status (OR 1.60, 95% CI 1.52 to 1.68), being an ex-smoker (OR 1.12, 95% CI 1.06 to 1.19) and hypertension (OR 1.07, 95% CI 1.03 to 1.17). Conclusions: The volume and quality of DOAC prescribing has increased yearly. Future interventions to augment quality of anticoagulant management should target disparities in adherence.

ABSTRACT:

Diabetes mellitus (DM) is a serious, chronic condition affecting 2.3 million people in the UK and consuming over 5% of the total National Health Service (NHS) budget. The World Health Organization (WHO) has produced a classification of diabetes which should help ensure consistent diagnosis and management of cases. However, recent quality based targets for diabetes in the UK only allow for people with Type 1 or Type 2 diabetes to be included in the disease register.

Computerised Medical Record (CMR) data are widely used for secondary purposes such as service evaluation and epidemiological research. Data are increasingly aggregated from different medical facilities with various CMR vendors over time. It is increasingly difficult to manage the large quantity of data. Experiential learning in diabetes and chronic kidney disease (CKD) suggests simplistic processing can lead to errors. To maximise analytical ability for the Quality Improvement in CKD (QICKD) trial, we developed an agile data management process. By removing the need to import and process data in a relational data-base, we reduced processing and analysis time. We demonstrated usage of our new agile method to rapidly develop complex queries to identify how blood pressure varied between patients included or excluded from Quality and Outcomes Frameworks (QOF) pay-for-performance (P4P) targets in UK primary care. We describe a novel specification language that allows clinicians to focus on identifying variables to extract useful information from CMRs. Data for research questions were available in <1hour instead of longer times previously required through use of an SQL database.

Objectives To investigate the deployment of physician associates (PAs); the factors supporting and inhibiting their employment and their contribution and impact on patients’ experience and outcomes and the organisation of services. Design Mixed methods within a case study design, using interviews, observations, work diaries and documentary analysis. Setting Six acute care hospitals in three regions of England in 2016–2017. Participants 43 PAs, 77 other health professionals, 28 managers, 28 patients and relatives. Results A key influencing factor supporting the employment of PAs in all settings was a shortage of doctors. PAs were found to be acceptable, appropriate and safe members of the medical/surgical teams by the majority of doctors, managers and nurses. They were mainly deployed to undertake inpatient ward work in the medical/surgical team during core weekday hours. They were reported to positively contribute to: continuity within their medical/surgical team, patient experience and flow, inducting new junior doctors, supporting the medical/surgical teams’ workload, which released doctors for more complex patients and their training. The lack of regulation and attendant lack of authority to prescribe was seen as a problem in many but not all specialties. The contribution of PAs to productivity and patient outcomes was not quantifiable separately from other members of the team and wider service organisation. Patients and relatives described PAs positively but most did not understand who and what a PA was, often mistaking them for doctors. Conclusions This study offers new insights concerning the deployment and contribution of PAs in medical and surgical specialties in English hospitals. PAs provided a flexible addition to the secondary care workforce without drawing from existing professions. Their utility in the hospital setting is unlikely to be completely realised without the appropriate level of regulation and authority to prescribe medicines and order ionising radiation within their scope of practice.

Purpose The University of Surrey-Lilly Real World Evidence (RWE) diabetes cohort has been established to provide insights into the management of type 2 diabetes mellitus (T2DM). There are 3 areas of study due to be conducted to provide insights into T2DM management: exploration of medication adherence, thresholds for changing diabetes therapies, and ethnicity-related or socioeconomic-related disparities in management. This paper describes the identification of a cohort of people with T2DM which will be used for these analyses, through a case finding algorithm, and describes the characteristics of the identified cohort. Participants A cohort of people with T2DM was identified from the Royal College of General Practitioners Research and Surveillance Centre (RCGP RSC) data set. This data set comprises electronic patient records collected from a nationally distributed sample of 130 primary care practices across England with scope to increase the number of practices to 200. Findings to date A cohort (N=58 717) of adults with T2DM was identified from the RCGP RSC population (N=1 260 761), a crude prevalence of diabetes of 5.8% in the adult population. High data quality within the practice network and an ontological approach to classification resulted in a high level of data completeness in the T2DM cohort; ethnicity identification (82.1%), smoking status (99.3%), alcohol use (93.3%), glycated haemoglobin (HbA1c; 97.9%), body mass index (98.0%), blood pressure (99.4%), cholesterol (87.4%) and renal function (97.8%). Data completeness compares favourably to other, similarly large, observational cohorts. The cohort comprises a distribution of ages, socioeconomic and ethnic backgrounds, diabetes complications, and comorbidities, enabling the planned analyses. Future plans Regular data uploads from the RCGP RSC practice network will enable this cohort to be followed prospectively. We will investigate medication adherence, explore thresholds and triggers for changing diabetes therapies, and investigate any ethnicity-related or socioeconomic-related disparities in diabetes management.

Aims: The sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral diabetes medication. Prescribing of these agents was initially limited to secondary care but is now moving into primary care. We analyse the current use of this drug class in primary care.

Aim To characterize the risk uveitis, scleritis or episcleritis in relation to diabetes, glycaemic control, and co-existence of retinopathy. Methods Using the Royal College of General Practitioners Research and Surveillance Centre database, we established the prevalence of acute uveitis and scleritis or episcleritis over a six-year period among populations without(n = 889,856) and with diabetes(n = 48,584). We evaluated the impact of glycaemic control on disease risk. Regression modeling was used to identify associations, adjusting for clinical and demographic confounders. Results Incidence of acute uveitis was higher among patients with diabetes; Type 1 OR:2.01 (95% CI 1.18–3.41; p = 0.009), and Type 2 OR:1.23 (1.05–1.44; p = 0.01). Glycaemic control was established as an important effect modifier for uveitis risk, whereby those with poorer control suffered higher disease burden. Results confirmed a dose-response relationship such that very poor glycaemic control OR:4.72 (2.58–8.65; p 

Health care, in common with many other industries, is generating large amounts of routine data, data that are challenging to process, analyse or curate, so-called 'big data'. A challenge for health informatics is to make sense of these data. Part of the answer will come from the development of ontologies that support the use of heterogeneous data sources and the development of intermediate processors of health information (IPHI). IPHI will sit between the generators of health data and information, often the providers of health care, and the managers, commissioners, policy makers, researchers, and the pharmaceutical and other healthcare industries. They will create a health ecosystem by processing data in a way that stimulates improved data quality and potentially healthcare delivery by providers of health care, and by providing greater insights to legitimate users of data. Exemplars are provided of how a health ecosystem might be encouraged and developed to promote patient safety and more efficient health care. These are in the areas of how to integrate data around the unsafe use of alcohol and to explore vaccine safety. A challenge for IPHI is how to ensure that their processing of data is valid, safe and maintains privacy. Development of the healthcare ecosystem and IPHI should be actively encouraged internationally. Governments, regulators and providers of health care should facilitate access to health data and the use of national and international comparisons to monitor standards. However, most importantly, they should pilot new methods of improving quality and safety through the intermediate processing of health data.

Background: While population estimates suggest high vaccine effectiveness against SARS-CoV-2 infection, the protection for health care workers, who are at higher risk of SARS-CoV-2 exposure, is less understood. Methods: We conducted a national cohort study of health care workers in Wales (UK) from 7 December 2020 to 30 September 2021. We examined uptake of any COVID-19 vaccine, and the effectiveness of BNT162b2 mRNA (Pfizer-BioNTech) against polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection. We used linked and routinely collected national-scale data within the SAIL Databank. Data were available on 82,959 health care workers in Wales, with exposure extending to 26 weeks after second doses. Results: Overall vaccine uptake was high (90%), with most health care workers receiving the BNT162b2 vaccine (79%). Vaccine uptake differed by age, staff role, socioeconomic status; those aged 50-59 and 60+ years old were 1.6 times more likely to get vaccinated than those aged 16-29. Medical and dental staff, and Allied Health Practitioners were 1.5 and 1.1 times more likely to get vaccinated, compared to nursing and midwifery staff. The effectiveness of the BNT162b2 vaccine was found to be strong and consistent across the characteristics considered; 52% three to six weeks after first dose, 86% from two weeks after second dose, though this declined to 53% from 22 weeks after the second dose. Conclusions: With some variation in rate of uptake, those who were vaccinated had a reduced risk of PCRconfirmed SARS-CoV-2 infection, compared to those unvaccinated. Second dose has provided stronger protection for longer than first dose but our study is consistent with waning from seven weeks onwards. (c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

IntroductionThe 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 analysisWe 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 disseminationWe 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.

Background In the UK, type 2 diabetes mellitus (T2D) is largely managed in primary care. Delay in the intensification to injectable therapy, a form of clinical inertia, is associated with worse glycaemic control. UK general practice is highly computerised, with care being recorded on computerised medical record systems; this allows for quantitative analysis of clinical care but not of the underpinning decision-making process. The aim of this study is to investigate perceptions of patients and clinicians in primary care on the initiation of injectable therapies in T2D, and the context within which those decisions are made. Methods This is a mixed methods study, taking a “realist evaluation” approach. The qualitative components comprise focus groups, interviews, and video recordings of simulated surgeries; the quantitative analysis: an overview of participating practices, elements of the video recording, and an online survey. We will recruit primary care clinicians (general practitioners and nurses) and patients from a representative sample of practices within the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network. Participants will be patients with T2D, and primary care clinicians. Focus groups and semi-structured interviews will be recorded, transcribed verbatim and analysed using Framework Analysis. The simulated surgeries will include cases that might be escalated to injectable therapy. The consultation will be reviewed using the Calgary-Cambridge model to assess communication and determination of adherence to national prescribing guidelines. We will conduct multi-channel video recording including screen capture, clinician and patient facial expressions, wide angle view of the consultation, and the computerised medical record screen. This allows annotation and qualitative analysis of the video recordings, and statistical analyses for the quantitative data. We will also conduct an online survey of primary care clinicians’ attitudes to, and perceptions of, initiation of injectable therapies, which will be analysed using summary statistics. Discussion Results aim to provide a detailed insight into the dynamic two-way decision-making process underpinning use of injectable therapy for T2D. The study will provide insights into clinical practice and enable the development of training, interventions and guidelines that may facilitate, where appropriate, the intensification to injectable therapy.

Background: Online access to computerized medical records has the potential to improve convenience, satisfaction, and care for patients, and to facilitate more efficient organization and delivery of care. Objective: The objective of this review is to explore the use and impact of having online access to computerized medical records and services for patients with type 2 diabetes mellitus in primary care. Methods: Multiple international databases including Medline, Embase, CINAHL, PsycINFO and the Cochrane Library were searched between 2004 and 2016. No limitations were placed on study design, though we applied detailed inclusion and exclusion criteria to each study. Thematic analysis was used to synthesize the evidence. The Mixed Methods Appraisal Toolkit was used to appraise study quality. Results: A search identified 917 studies, of which 28 were included. Five themes were identified: (1) disparities in uptake by age, gender, ethnicity, educational attainment, and number of comorbidities, with young men in full-time employment using these services most; (2) improved health outcomes: glycemic control was improved, but blood pressure results were mixed; (3) self-management support from improved self-care and shared management occurred especially soon after diagnosis and when complications emerged. There was a generally positive effect on physician-patient relationships; (4) accessibility: patients valued more convenient access when online access to computerized medical records and services work; and (5) technical challenges, barriers to use, and system features that impacted patient and physician use. The Mixed Methods Appraisal Toolkit rated 3 studies as 100%, 19 studies as 75%, 4 studies as 50%, and 1 study scored only 25%. Conclusions: Patients valued online access to computerized medical records and services, although in its current state of development it may increase disparities. Online access to computerized medical records appears to be safe and is associated with improved glycemic control, but there was a lack of rigorous evidence in terms of positive health outcomes for other complications, such as blood pressure. Patients remain concerned about how these systems work, the rules, and timeliness of using these systems.

During COVID-19 vaccination programmes, new safety signals have emerged for vaccines, including extremely rare cases of thrombosis with thrombocytopaenia syndrome (TTS). Background event rates before and during the pandemic are essential for contextualisation of such infrequent events. In the literature, most studies do not report an overall TTS event rate. Rather, background rates are mainly reported for subtypes of thrombotic/thromboembolic diagnoses included in the TTS clinical definition mostly by anatomical location, with reported rates for TTS subtypes varying widely. The objective of this study was to report prepandemic TTS background event rates in the general population. Prepandemic background TTS rates were generated via secondary data analysis using a cohort design in the IBM Truven MarketScan (now Merative MarketScan) US health insurance claims database, from 1 January 2019 to 31 December 2019. Two algorithms were applied: thrombocytopaenia occurring±7 days (algorithm 1) or occurring 1 day prior to ≤14 days after the thrombotic/thromboembolic event (algorithm 2). The study population derived from the MarketScan database analysis included approximately 9.8 million adults (aged ≥18 years; mean age 45 years, 52% females). Using this study population, prepandemic background TTS incidence was estimated as 9.8-11.1 per 100 000 person-years. Event rates were higher in males and increased with age. Similar patterns were observed with both algorithms. This study presents an estimate of aggregate prepandemic background TTS event rates including by type of thrombosis/thromboembolism and age group. The background event rates are dependent on the precision of capturing underlying TTS events in variable data sources, and the ability of electronic health records or insurance claims databases to reflect the TTS clinical definition. Differences between reported event rates demonstrate that estimating background event rates for rare, unprecedented safety events is methodologically challenging.

Background: Over 70% of the health-care budget in England is spent on the care of people with long-term conditions (LTCs), and a major cost component is unscheduled health care. Psychological morbidity is high in people with LTCs and is associated with a range of adverse outcomes, including increased mortality, poorer physical health outcomes, increased health costs and service utilisation. Objectives: The aim of this programme of research was to examine the relationship between psychological morbidity and use of unscheduled care in people with LTCs, and to develop a psychosocial intervention that would have the potential to reduce unscheduled care use. We focused largely on emergency hospital admissions (EHAs) and attendances at emergency departments (EDs). Design: A three-phase mixed-methods study. Research methods included systematic reviews; a longitudinal prospective cohort study in primary care to identify people with LTCs at risk of EHA or ED admission; a replication study in primary care using routinely collected data; an exploratory and feasibility cluster randomised controlled trial in primary care; and qualitative studies to identify personal reasons for the use of unscheduled care and factors in routine consultations in primary care that may influence health-care use. People with lived experience of LTCs worked closely with the research team. Setting: Primary care. Manchester and London. Participants: People aged ≥ 18 years with at least one of four common LTCs: asthma, coronary heart disease, chronic obstructive pulmonary disease (COPD) and diabetes. Participants also included health-care staff. Results: Evidence synthesis suggested that depression, but not anxiety, is a predictor of use of unscheduled care in patients with LTCs, and low-intensity complex interventions reduce unscheduled care use in people with asthma and COPD. The results of the prospective study were that depression, not having a partner and life stressors, in addition to prior use of unscheduled care, severity of illness and multimorbidity, were independent predictors of EHA and ED admission. Approximately half of the cost of health care for people with LTCs was accounted for by use of unscheduled care. The results of the replication study, carried out in London, broadly supported our findings for risk of ED attendances, but not EHAs. This was most likely due to low rates of detection of depression in general practitioner (GP) data sets. Qualitative work showed that patients were reluctant to use unscheduled care, deciding to do so when they perceived a serious and urgent need for care, and following previous experience that unscheduled care had successfully and unquestioningly met similar needs in the past. In general, emergency and primary care doctors did not regard unscheduled care as problematic. We found there are missed opportunities to identify and discuss psychosocial issues during routine consultations in primary care due to the ‘overmechanisation’ of routine health-care reviews. The feasibility trial examined two levels of an intervention for people with COPD: we tried to improve the way in which practices manage patients with COPD and developed a targeted psychosocial treatment for patients at risk of using unscheduled care. The former had low acceptability, whereas the latter had high acceptability. Exploratory health economic analyses suggested that the practice-level intervention would be unlikely to be cost-effective, limiting the value of detailed health economic modelling. Limitations: The findings of this programme may not apply to all people with LTCs. It was conducted in an area of high social deprivation, which may limit the generalisability to more affluent areas. The response rate to the prospective longitudinal study was low. The feasibility trial focused solely on people with COPD. Conclusions: Prior use of unscheduled care is the most powerful predictor of unscheduled care use in people with LTCs. However, psychosocial factors, particularly depression, are important additional predictors of use of unscheduled care in patients with LTCs, independent of severity and multimorbidity. Patients and health-care practitioners are unaware that psychosocial factors influence health-care use, and such factors are rarely acknowledged or addressed in consultations or discussions about use of unscheduled care. A targeted patient intervention for people with LTCs and comorbid depression has shown high levels of acceptability when delivered in a primary care context. An intervention at the level of the GP practice showed little evidence of acceptability or cost-effectiveness. Future work: The potential benefits of case-finding for depression in patients with LTCs in primary care need to be evaluated, in addition to further evaluation of the targeted patient intervention.

Background The COVID-19 pandemic is a complex global public health crisis presenting clinical, organisational and system-wide challenges. Different research perspectives on health are needed in order to manage and monitor this crisis. Performance intelligence is an approach that emphasises the need for different research perspectives in supporting health systems' decision-makers to determine policies based on well-informed choices. In this paper, we present the viewpoint of the Innovative Training Network for Healthcare Performance Intelligence Professionals (HealthPros) on how performance intelligence can be used during and after the COVID-19 pandemic. Discussion A lack of standardised information, paired with limited discussion and alignment between countries contribute to uncertainty in decision-making in all countries. Consequently, a plethora of different non-data-driven and uncoordinated approaches to address the outbreak are noted worldwide. Comparative health system research is needed to help countries shape their response models in social care, public health, primary care, hospital care and long-term care through the different phases of the pandemic. There is a need in each phase to compare context-specific bundles of measures where the impact on health outcomes can be modelled using targeted data and advanced statistical methods. Performance intelligence can be pursued to compare data, construct indicators and identify optimal strategies. Embracing a system perspective will allow countries to take coordinated strategic decisions while mitigating the risk of system collapse.A framework for the development and implementation of performance intelligence has been outlined by the HealthPros Network and is of pertinence. Health systems need better and more timely data to govern through a pandemic-induced transition period where tensions between care needs, demand and capacity are exceptionally high worldwide. Health systems are challenged to ensure essential levels of healthcare towards all patients, including those who need routine assistance. Conclusion Performance intelligence plays an essential role as part of a broader public health strategy in guiding the decisions of health system actors on the implementation of contextualised measures to tackle COVID-19 or any future epidemic as well as their effect on the health system at large. This should be based on commonly agreed-upon standardised data and fit-for-purpose indicators, making optimal use of existing health information infrastructures. The HealthPros Network can make a meaningful contribution.

BackgroundTo develop items for an early warning score (RECAP: REmote COVID-19 Assessment in Primary Care) for patients with suspected COVID-19 who need escalation to next level of care.MethodsThe study was based in UK primary healthcare. The mixed-methods design included rapid review, Delphi panel, interviews, focus groups and software development. Participants were 112 primary care clinicians and 50 patients recovered from COVID-19, recruited through social media, patient groups and snowballing. Using rapid literature review, we identified signs and symptoms which are commoner in severe COVID-19. Building a preliminary set of items from these, we ran four rounds of an online Delphi panel with 72 clinicians, the last incorporating fictional vignettes, collating data on R software. We refined the items iteratively in response to quantitative and qualitative feedback. Items in the penultimate round were checked against narrative interviews with 50 COVID-19 patients. We required, for each item, at least 80% clinician agreement on relevance, wording and cut-off values, and that the item addressed issues and concerns raised by patients. In focus groups, 40 clinicians suggested further refinements and discussed workability of the instrument in relation to local resources and care pathways. This informed design of an electronic template for primary care systems.ResultsThe prevalidation RECAP-V0 comprises a red flag alert box and 10 assessment items: pulse, shortness of breath or respiratory rate, trajectory of breathlessness, pulse oximeter reading (with brief exercise test if appropriate) or symptoms suggestive of hypoxia, temperature or fever symptoms, duration of symptoms, muscle aches, new confusion, shielded list and known risk factors for poor outcome. It is not yet known how sensitive or specific it is.ConclusionsItems on RECAP-V0 align strongly with published evidence, clinical judgement and patient experience. The validation phase of this study is ongoing.Trial registration numberNCT04435041.

ObjectivesTo assess disease trends, testing practices, community surveillance, case-fatality and excess deaths in children as compared with adults during the first pandemic peak in England.SettingEngland.ParticipantsChildren with COVID-19 between January and May 2020.Main outcome measuresTrends in confirmed COVID-19 cases, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity rates in children compared with adults; community prevalence of SARS-CoV-2 in children with acute respiratory infection (ARI) compared with adults, case-fatality rate in children with confirmed COVID-19 and excess childhood deaths compared with the previous 5 years.ResultsChildren represented 1.1% (1,408/129,704) of SARS-CoV-2 positive cases between 16 January 2020 and 3 May 2020. In total, 540 305 people were tested for SARS-COV-2 and 129,704 (24.0%) were positive. In children aged

The European Medicines Agency (EMA) requires vaccine manufacturers to conduct enhanced real-time surveillance of seasonal influenza vaccination. The EMA has specified a list of adverse events of interest to be monitored. The EMA sets out 3 different ways to conduct such surveillance: (1) active surveillance, (2) enhanced passive surveillance, or (3) electronic health record data mining (EHR-DM). English general practice (GP) is a suitable setting to implement enhanced passive surveillance and EHR-DM. This study aimed to test the feasibility of conducting enhanced passive surveillance in GP using the yellow card scheme (adverse events of interest reporting cards) to determine if it has any advantages over EHR-DM alone. A total of 9 GPs in England participated, of which 3 tested the feasibility of enhanced passive surveillance and the other 6 EHR-DM alone. The 3 that tested EPS provided patients with yellow (adverse events) cards for patients to report any adverse events. Data were extracted from all 9 GPs' EHRs between weeks 35 and 49 (08/24/2015 to 12/06/2015), the main period of influenza vaccination. We conducted weekly analysis and end-of-study analyses. Our GPs were largely distributed across England with a registered population of 81,040. In the week 49 report, 15,863/81,040 people (19.57% of the registered practice population) were vaccinated. In the EPS practices, staff managed to hand out the cards to 61.25% (4150/6776) of the vaccinees, and of these cards, 1.98% (82/4150) were returned to the GP offices. Adverse events of interests were reported by 113 /7223 people (1.56%) in the enhanced passive surveillance practices, compared with 322/8640 people (3.73%) in the EHR-DM practices. Overall, we demonstrated that GPs EHR-DM was an appropriate method of enhanced surveillance. However, the use of yellow cards, in enhanced passive surveillance practices, did not enhance the collection of adverse events of interests as demonstrated in this study. Their return rate was poor, data entry from them was not straightforward, and there were issues with data reconciliation. We concluded that customized cards prespecifying the EMA's adverse events of interests, combined with EHR-DM, were needed to maximize data collection. RR2-10.1136/bmjopen-2016-015469.

Background: Mental health problems are common in England, and new medications potentially offer equal or greater efficacy with increased patient safety and fewer side-effects. Objective: To examine the use of psychotropic medications in primary care, in particular the use of more modern drug therapies. Subjects and setting: Using routinely collected computer data from 12 general practices with a combined list size of 117 000. Method: We collected anonymised data from general practice computer systems using MIQUEST (Morbidity Information Query and Export Syntax - a Department of Health-sponsored data extraction tool). Data were aggregated, cleaned and processed using an established methodology, then imported into a statistical package for analysis. Results: The use of psychotropic medication increased with age. Over one-third (35%) of women and one-quarter (23.8%) of men of the study population aged over 85 years were prescribed at least one psychotropic medication in the last year (P < 0.001). At all ages, women are twice as likely to be prescribed psychotropic medication, though no more likely to be prescribed multiple therapies. One-quarter of those with a diagnosis of severe and enduring mental illness (SMI) were not taking any psychotropic medication. Over half of those with SMI on medication are taking more than one medication. The proportion of people prescribed atypical anti-psychotics has risen from 30% to 50%, with a corresponding fall in the use of older anti-psychotics. Twenty-one percent of females have been prescribed antidepressants, 14% in the last year. In contrast to anti-psychotics, the proportion of people prescribed more modern antidepressants has increased slightly. Conclusions: Females and older people are much more likely to receive psychotropic medications. Further research is needed to explore why the pattern of prescribing differs from what is known about the pattern of mental health problems. © 2006 Radcliffe Publishing.

Background Hypertension is a major cause of preventable disability and death globally and affects more than one in four adults in England. Unwarranted variation is variation in access, quality, outcome or value which is unexplained by differences in the condition or patient characteristics and which reduces quality and efficiency. Distinguishing unwarranted from variation due to clinical, organisational or patient factors can be challenging. We carried out this study to explore inter-practice variation in the diagnosis and management of hypertension in the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network database, a large, representative surveillance database. Methods and finding We carried out a cross-sectional study using primary care data extracted from the electronic health records of 1,271,419 adults registered at RCGP RSC general practices on 31st December 2016. Logistic regression was used to indirectly standardise practice-level hypertension prevalence and control against the RCGP RSC population, adjusted for age, gender, ethnicity, deprivation, co-morbidity, NHS region and practice size. Inter-practice variation was demonstrated using funnel plots with 95% and 99.8% control limits. The prevalence of detected hypertension was 18.4% (95% CI 18.4-18.5), n = 234,165. Uncontrolled hypertension was present in 146,553 of 196,052 individuals, 25.2% (25.1-25.4), in whom blood pressure had been recorded in the previous year. Hypertension management varied markedly between practices with a three-fold difference in prevalence, 13.5-38.4%, and a four-fold difference in the proportion of uncontrolled hypertension, 11.8-47.9%. Despite adjustment for sociodemographic and practice characteristics funnel plots demonstrated marked over-dispersion. Conclusions Substantial variation in the prevalence of diagnosed hypertension and the management of hypertension was only partially explained by characteristics captured within a routine data-set. The over-dispersion suggests variation is not fully explained by these factors and that context, behaviour and processes of care delivery may contribute to variation. Routine data sources in isolation to not provide sufficient contextual data to diagnose the causes of variation.

Measures of the contribution of influenza to Streptococcus pneumoniae infections, both in the seasonal and pandemic setting, are needed to predict the burden of secondary bacterial infections in future pandemics to inform stockpiling. The magnitude of the interaction between these two pathogens has been difficult to quantify because both infections are mainly clinically diagnosed based on signs and symptoms; a combined viral-bacterial testing is rarely performed in routine clinical practice; and surveillance data suffer from confounding problems common to all ecological studies. We proposed a novel multivariate model for age-stratified disease incidence, incorporating contact patterns and estimating disease transmission within and across groups. We used surveillance data from England over the years 2009 to 2017. Influenza infections were identified through the virological testing of samples taken from patients diagnosed with influenza-like illness (ILI) within the sentinel scheme run by the Royal College of General Practitioners (RCGP). Invasive pneumococcal disease (IPD) cases were routinely reported to Public Health England (PHE) by all the microbiology laboratories included in the national surveillance system. IPD counts at week t, conditional on the previous time point t-1, were assumed to be negative binomially distributed. Influenza counts were linearly included in the model for the mean IPD counts along with an endemic component describing some seasonal background and an autoregressive component mimicking pneumococcal transmission. Using age-specific counts, Akaike information criterion (AIC)-based model selection suggested that the best fit was obtained when the endemic component was expressed as a function of observed temperature and rainfall. Pneumococcal transmission within the same age group was estimated to explain 33.0% (confidence interval [CI] 24.9%-39.9%) of new cases in the elderly, whereas 50.7% (CI 38.8%-63.2%) of incidence in adults aged 15-44 years was attributed to transmission from another age group. The contribution of influenza on IPD during the 2009 pandemic also appeared to vary greatly across subgroups, being highest in school-age children and adults (18.3%, CI 9.4%-28.2%, and 6.07%, CI 2.83%-9.76%, respectively). Other viral infections, such as respiratory syncytial virus (RSV) and rhinovirus, also seemed to have an impact on IPD: RSV contributed 1.87% (CI 0.89%-3.08%) to pneumococcal infections in the 65+ group, whereas 2.14% (CI 0.87%-3.57%) of cases in the group of 45- to 64-year-olds were attributed to rhinovirus. The validity of this modelling strategy relies on the assumption that viral surveillance adequately represents the true incidence of influenza in the population, whereas the small numbers of IPD cases observed in the younger age groups led to significant uncertainty around some parameter estimates. Our estimates suggested that a pandemic wave of influenza A/H1N1 with comparable severity to the 2009 pandemic could have a modest impact on school-age children and adults in terms of IPD and a small to negligible impact on infants and the elderly. The seasonal impact of other viruses such as RSV and rhinovirus was instead more important in the older population groups.

Aims: The relationship between glycaemic control and lipid metabolism in diabetes is complicated and yet to be fully elucidated. Here we aim to characterise the relationship between glycaemic control and serum triglyceride levels in a population with Type 2 diabetes

Background: Medical research increasingly requires the linkage of data from different sources. Conducting a requirements analysis for a new application is an established part of software engineering, but rarely reported in the biomedical literature; and no generic approaches have been published as to how to link heterogeneous health data. Methods: Literature review, followed by a consensus process to define how requirements for research, using, multiple data sources might be modeled. Results: We have developed a requirements analysis: i-ScheDULEs - The first components of the modeling process are indexing and create a rich picture of the research study. Secondly, we developed a series of reference models of progressive complexity: Data flow diagrams (DFD) to define data requirements; unified modeling language (UML) use case diagrams to capture study specific and governance requirements; and finally, business process models, using business process modeling notation (BPMN). Discussion: These requirements and their associated models should become part of research study protocols.

Despite the evidence available on the epidemiology of diabetic foot ulcers and associated complications, it is not clear how specific organizational aspects of health care systems can positively affect their clinical trajectory. We aim to evaluate the impact of organizational aspects of care on lower extremity amputation rates among people with type 2 diabetes affected by foot ulcers. We conducted a systematic review of the scientific literature published between 1999 and 2019, using the following key terms as search criteria: people with type 2 diabetes, diagnosed with diabetic foot ulcer, treated with specific processes and care pathways, and LEA as primary outcome. Overall results were reported as pooled odds ratios and 95% confidence intervals obtained using fixed and random effects models. A total of 57 studies were found eligible, highlighting the following arrangements: dedicated teams, care pathways and protocols, multidisciplinary teams, and combined interventions. Among them, seven studies qualified for a meta-analysis. According to the random effects model, interventions including any of the four arrangements were associated with a 29% reduced risk of any type of lower extremity amputation (OR = 0.71; 95% CI 0.52-0.96). The effect was larger when focusing on major LEAs alone, leading to a 48% risk reduction (OR = 0.52; 95% CI 0.30-0.91). Specific organizational arrangements including multidisciplinary teams and care pathways can prevent half of the amputations in people with diabetes and foot ulcers. Further studies using standardized criteria are needed to investigate the cost-effectiveness to facilitate wider implementation of improved organizational arrangements. Similarly, research should identify specific roadblocks to translating evidence into action. These may be structures and processes at the health system level, e.g. availability of professionals with the right skillset, reimbursement mechanisms, and clear organizational intervention implementation guidelines.

Limited medication adherence and persistence with treatment are barriers to successful management of type 2 diabetes (T2D). We searched MEDLINE, EMBASE, the Cochrane Library, the Register of Controlled Trials, PsychINFO and CINAHL for observational and interventional studies that compared the adherence or persistence associated with 2 or more glucose-lowering medications in people with T2D. Where 5 or more studies provided the same comparison, a random-effects meta-analysis was performed, reporting mean difference (MD) or odds ratio (OR) for adherence or persistence, depending on the pooled study outcomes. We included a total of 48 studies. Compared with metformin, adherence (%) was better for sulphonylureas (5 studies; MD 10.6%, 95% confidence interval [CI] 6.5-14.7) and thiazolidinediones (TZDs; 6 studies; MD 11.3%, 95% CI 2.7%-20.0%). Adherence to TZDs was marginally better than adherence to sulphonylureas (5 studies; MD 1.5%, 95% CI 0.1-2.9). Dipeptidyl peptidase-4 inhibitors had better adherence than sulphonylureas and TZDs. Glucagon-like peptide-1 receptor agonists had higher rates of discontinuation than long-acting analogue insulins (6 studies; OR 1.95; 95% CI 1.17-3.27). Longacting insulin analogues had better persistence than human insulins (5 studies; MD 43.1 days; 95% CI 22.0-64.2). The methods used to define adherence and persistence were highly variable.

Background: Concerns have been raised that Angiotensin Converting Enzyme-Inhibitors (ACE-I) and Angiotensin Receptor Blockers (ARB) might facilitate transmission of SARS-CoV-2 leading to more severe coronavirus disease (COVID-19) disease and an increased risk of mortality. We aimed to investigate the association between ACE-I/ARB treatment and risk of death amongst people with COVID-19 in the first six months of the pandemic. Methods: We identified a cohort of adults diagnosed with either confirmed or probable COVID-19 (from 1st January – 21st June 2020) using computerised medical records from the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care database. This comprised 465 general practices in England, UK with a nationally representative population of 3.7 million people. We constructed mixed-effects logistic regression models to quantify the association between ACE-I/ARBs and all-cause mortality among people with COVID-19, adjusted for sociodemographic factors, co-morbidities, concurrent medication, smoking status, practice clustering and household number. Results: There were 9,586 COVID-19 cases in the sample and 1,463 (15.3%) died during the study period between 01.01.2020 and 21.06.2020. In adjusted analysis ACE-I and ARBs were not associated with all-cause mortality (adjusted OR 1.02, 95% CI 0.85 to 1.21 and 0.84, 95% CI 0.67 to 1.07 respectively). Conclusion: Use of ACE-I/ARB, which are commonly used drugs, did not alter the odds of all-cause mortality amongst people diagnosed with COVID-19. Our findings should inform patient and prescriber decisions concerning continued use of these medications during the pandemic. HDM is an National Institute for Health Research funded Academic Clinical Lecturer and received NIHR SPCR funding for this project (SPCR2014-10043). SJG is supported by an MRC Epidemiology Unit programme: MC_UU_12015/4. The University of Cambridge has received salary support in respect of SJG from the NHS in the East of England through the Clinical Academic Reserve. JHC acknowledges personal support from the British Heart Foundation (FS/14/55/30806) and Cancer Research UK (C5255/A18085) through the Cancer Research UK Oxford Centre

Aims. To compare different packages of care across care providers in Scotland on foot-related outcomes. Methods. A retrospective cohort study with primary and secondary care electronic health records from the Scottish Diabetes Registry, including 6,845 people with type 2 diabetes and a first foot ulcer occurring between 2013 and 2017. We assessed the association between exposure to care processes and major lower extremity amputation and death. Proportional hazards were used for time-to-event univariate and multivariate analyses, adjusting for case-mix characteristics and care processes. Results were expressed in terms of hazard ratios with 95% confidence intervals. Results. 2,243 (32.7%) subjects had a major amputation or death. Exposure to all nine care processes at all ages ( HR = 0.63 ; 95% CI: 0.58-0.69; p < .001 ) and higher foot care attendance in people aged >70 years ( HR = 0.88 ; 0.78-0.99; p = .03 ) were associated with longer major amputation-free survival. Waiting time ≥ 12 weeks between ulceration and clinic attendance was associated with worse outcomes ( HR = 1.59 ; 1.37-1.84; p < .001 ). In people > 70 years, minor amputations were associated with improved major amputation-free survival ( HR = 0.69 ; 0.52-0.92; p = .01 ). Conclusions. Strict adherence to a standardised package of general diabetes care before foot ulceration, timely foot care after ulceration, and specific treatment pathways were associated with longer major amputation-free survival among a large cohort of people with type 2 diabetes in Scotland, with a larger impact on older age groups.

Background Back to school (BTS) asthma has been previously reported in children; however, its epidemiology and associated healthcare burden are unclear. We aimed to describe the timing and magnitude of BTS asthma using surveillance data from different health services in England.Methods Asthma morbidity data from emergency department attendances and general practitioner (GP) consultations between April 2012 and December 2016 were used from national syndromic surveillance systems in England. Age-specific and sex-specific rates and time series of asthma peaks relative to school term dates were described. The timing of a BTS excess period and adjusted rates of asthma relative to a baseline period were estimated using cumulative sum control chart plots and negative binomial regression.Results BTS asthma among children aged below 15 years was most pronounced at the start of the school year in September. This effect was not present among those aged 15 years and above. After controlling for sex and study year, the adjusted daily rate of childhood GP in-hours asthma consultations was 2.5–3 times higher in the BTS excess period, with a significantly higher effect among children aged 0–4 years. A distinct age-specific pattern of sex differences in asthma presentations was present, with a higher burden among males in children and among females aged over 15 years.ConclusionWe found evidence of a BTS asthma peak in children using surveillance data across a range of healthcare systems, supporting the need for further preventative work to reduce the impact of BTS asthma in children.

Introduction: Initiation of injectable therapies in type 2 diabetes (T2D) is often delayed, however the reasons why are not fully understood. Methods: A mixed methods study performed in sequential phases. Phase 1: focus groups with people with T2D (injectable naı¨venaı¨ve [n = 12] and experienced [n = 5]) and healthcare professionals (HCPs; nurses [n = 5] and general practitioners (GPs) [n = 7]) to understand their

Primary care provision is important in the delivery of health care but many countries face primary care workforce challenges. Increasing demand, enlarged workloads, and current and anticipated physician shortages in many countries have led to the introduction of mid-level professionals, such as Physician Assistants (PAs). Objective: This systematic review aimed to appraise the evidence of the contribution of PAs within primary care, defined for this study as general practice, relevant to the UK or similar systems.

The United Kingdom (UK) is in the third season of introducing universal paediatric influenza vaccination with a quadrivalent live attenuated influenza vaccine (LAIV). The 2015/16 season in the UK was initially dominated by influenza A(H1N1)pdm09 and then influenza of B/Victoria lineage, not contained in that season’s adult trivalent inactivated influenza vaccine (IIV). Overall adjusted end-of-season vaccine effectiveness (VE) was 52.4% (95% confidence interval (CI): 41.0–61.6) against influenza-confirmed primary care consultation, 54.5% (95% CI: 41.6–64.5) against influenza A(H1N1)pdm09 and 54.2% (95% CI: 33.1–68.6) against influenza B. In 2–17 year-olds, adjusted VE for LAIV was 57.6% (95% CI: 25.1 to 76.0) against any influenza, 81.4% (95% CI: 39.6–94.3) against influenza B and 41.5% (95% CI: −8.5 to 68.5) against influenza A(H1N1)pdm09. These estimates demonstrate moderate to good levels of protection, particularly against influenza B in children, but relatively less against influenza A(H1N1)pdm09. Despite lineage mismatch in the trivalent IIV, adults younger than 65 years were still protected against influenza B. These results provide reassurance for the UK to continue its influenza immunisation programme planned for 2016/17.

Background We investigated differences in risk of stroke, with all-cause mortality as a competing risk, in people newly diagnosed with atrial fibrillation (AF) who were commenced on either direct oral anticoagulants (DOACs) or warfarin treatment. Methods and results We conducted a retrospective cohort study of the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database (a network of 500 English general practices). We compared long term exposure to DOAC (n = 5,168) and warfarin (n = 7,451) in new cases of AF not previously treated with oral anticoagulants. Analyses included: survival analysis, estimating cause specific hazard ratios (CSHR), Fine-Gray analysis for factors affecting cumulative incidence of events occurring over time and a cumulative risk regression with time varying effects.We found no difference in CSHR between stroke 1.08 (0.72–1.63, p = 0.69) and all-cause mortality 0.93 (0.81–1.08, p = 0.37), or between the anticoagulant groups. Fine-Gray analysis produced similar results 1.07 (0.71–1.6 p = 0.75) for stroke and 0.93 (0.8–1.07, p = 0.3) mortality. The cumulative risk of mortality with DOAC was significantly elevated in early follow-up (67 days), with cumulative risk decreasing until 1,537 days and all-cause mortality risk significantly decreased coefficient estimate:: -0.23 (-0.38–0.01, p = 0.001); which persisted over seven years of follow-up. Conclusions In this large, contemporary, real world primary care study with longer follow-up, we found no overall difference in the hazard of stroke between warfarin and DOAC treatment for AF. However, there was a significant time-varying effect between anti-coagulant regimen on all-cause mortality, with DOACs showing better survival. This is a key methodological observation for future follow-up studies, and reassuring for patients and health care professionals for longer duration of therapy

Background Current UK vaccination policy is to offer future COVID-19 booster doses to individuals at high risk of serious illness from COVID-19, but it is still uncertain which groups of the population could benefit most. In response to an urgent request from the UK Joint Committee on Vaccination and Immunisation, we aimed to identify risk factors for severe COVID-19 outcomes (ie, COVID- 19-related hospitalisation or death) in individuals who had completed their primary COVID-19 vaccination schedule and had received the first booster vaccine. Methods We constructed prospective cohorts across all four UK nations through linkages of primary care, RT-PCR testing, vaccination, hospitalisation, and mortality data on 30 million people. We included individuals who received primary vaccine doses of BNT162b2 (tozinameran; Pfizer-BioNTech) or ChAdOx1 nCoV-19 (OxfordAstraZeneca) vaccines in our initial analyses. We then restricted analyses to those given a BNT162b2 or mRNA-1273 (elasomeran; Moderna) booster and had a severe COVID-19 outcome between Dec 20, 2021, and Feb 28, 2022 (when the omicron (B.1.1.529) variant was dominant). We fitted time-dependent Poisson regression models and calculated adjusted rate ratios (aRRs) and 95% CIs for the associations between risk factors and COVID-19-related hospitalisation or death. We adjusted for a range of potential covariates, including age, sex, comorbidities, and previous SARS-CoV-2 infection. Stratified analyses were conducted by vaccine type. We then did pooled analyses across UK nations using fixed-effect meta-analyses. Findings Between Dec 8, 2020, and Feb 28, 2022, 16 208 600 individuals completed their primary vaccine schedule and 13 836 390 individuals received a booster dose. Between Dec 20, 2021, and Feb 28, 2022, 59 510 (0.4%) of the primary vaccine group and 26 100 (0 .2%) of those who received their booster had severe COVID-19 outcomes. The risk of severe COVID-19 outcomes reduced after receiving the booster (rate change: 8.8 events per 1000 personyears to 7.6 events per 1000 person-years). Older adults (>= 80 years vs 18-49 years; aRR 3.60 [95% CI 3.45-3.75]), those with comorbidities (>= 5 comorbidities vs none; 9.51 [9.07-9.97]), being male (male vs female; 1.23 [1.20-1.26]), and those with certain underlying health conditions-in particular, individuals receiving immunosuppressants (yes vs no; 5.80 [5.53-6.09])-and those with chronic kidney disease (stage 5 vs no; 3.71 [2 .90- 4.74]) remained at high risk despite the initial booster. Individuals with a history of COVID-19 infection were at reduced risk (infected >= 9 months before booster dose vs no previous infection; aRR 0.41 [95% CI 0.29-0.58]). Interpretation Older people, those with multimorbidity, and those with specific underlying health conditions remain at increased risk of COVID-19 hospitalisation and death after the initial vaccine booster and should, therefore, be prioritised for additional boosters, including novel optimised versions, and the increasing array of COVID-19 therapeutics. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

New forms of evidence are needed to complement evidence generated from randomised controlled trials (RCTs). Real-World Evidence (RWE) is a potential new form of evidence, but remains undefined. This paper sets to fill that gap by defining RWE as the output from a rigorous research process which: (1) includes a clear a priori statement of a hypothesis to be tested or research question to be answered; (2) defines the data sources that will be used and critically appraises their strengths and weaknesses; and (3) applies appropriate methods, including advanced analytics. These elements should be set out in advance of the study commencing, ideally in a published protocol. The strengths of RWE studies are that they are more inclusive than RCTs and can enable an evidence base to be developed around real-world effectiveness and to start to address the complications of managing other real-world problems such as multimorbidity. Computerised medical record systems and big data provide a rich source of data for RWE studies. However, guidance is needed to help assess the rigour of RWE studies so that the strength of recommendations based on their output can be determined. Additionally, RWE advanced analytics methods need better categorisation and validation. We predict that the core role of RCTs will shift towards assessing safety and achieving regulatory compliance. RWE studies, notwithstanding their limitations, may become established as the best vehicle to assess efficacy.

There are limited data about the risk of asthma in people with diabetes. We examined the incidence of asthma in subjects with type 2 diabetes (T2DM) compared to controls, and the association with metformin, sulphonylureas and insulin therapy. We conducted a retrospective cohort study using a representative UK primary care database (N = 894 646 adults). We used 1:1 propensity score matching (age, gender, socio-economic deprivation, body mass index and smoking status) to match 29 217 pairs of T2DM cases and controls. We used Cox proportional hazard regression to compare the incidence of asthma in both groups over 8 years of follow-up. In those with T2DM, we used Cox proportional hazard regression to assess for any impact of antidiabetic medications on asthma incidence. Individuals with T2DM were less likely to develop asthma than matched controls (hazard ratio [HR] 0.85, 95% CI 0.77-0.93). Insulin increased the risk of incident asthma (HR 1.25, 95% CI 1.01-1.56), whilst metformin and sulphonylureas were associated with reduced risk (HR 0.80, 95% CI 0.69-0.93 and HR 0.76, 95% CI 0.60-0.97, respectively). There was no association with diabetes duration, complications or glycaemic control. T2DM may have a protective effect against asthma development. Insulin use was associated with an increased risk of asthma, while metformin and sulphonylureas reduced the risk in those with T2DM.

Every year in the UK there is a seasonal peak in morbidity and mortality during the coldest months. GPs have an important role in promoting winter wellness and we would like to advocate GPs placing more emphasis on a proactive approach designed to reduce risk among vulnerable individuals and families. Although some of the activities we already undertake contribute to this goal, others fall short, and few of us promote winter wellness in a coordinated way across our health and social care community. To maximise our effectiveness, primary care teams should be aware of the modifiable risk factors for excess winter mortality and morbidity; and actively manage these as part of planned as well as opportunistic care.

Disparities in type 2 diabetes (T2D) care provision and clinical outcomes have been reported in the last 2 decades in the UK. Since then, a number of initiatives have attempted to address this imbalance. The aim was to evaluate contemporary data as to whether disparities exist in glycaemic control, monitoring, and prescribing in people with T2D. A T2D cohort was identified from the Royal College of General Practitioners Research and Surveillance Centre dataset: a nationally representative sample of 164 primary care practices (general practices) across England. Diabetes healthcare provision and glucose-lowering medication use between 1 January 2012 and 31 December 2016 were studied. Healthcare provision included annual HbA1c, renal function (estimated glomerular filtration rate [eGFR]), blood pressure (BP), retinopathy, and neuropathy testing. Variables potentially associated with disparity outcomes were assessed using mixed effects logistic and linear regression, adjusted for age, sex, ethnicity, and socioeconomic status (SES) using the Index of Multiple Deprivation (IMD), and nested using random effects within general practices. Ethnicity was defined using the Office for National Statistics ethnicity categories: White, Mixed, Asian, Black, and Other (including Arab people and other groups not classified elsewhere). From the primary care adult population (n = 1,238,909), we identified a cohort of 84,452 (5.29%) adults with T2D. The mean age of people with T2D in the included cohort at 31 December 2016 was 68.7 ± 12.6 years; 21,656 (43.9%) were female. The mean body mass index was 30.7 ± SD 6.4 kg/m2. The most deprived groups (IMD quintiles 1 and 2) showed poorer HbA1c than the least deprived (IMD quintile 5). People of Black ethnicity had worse HbA1c than those of White ethnicity. Asian individuals were less likely than White individuals to be prescribed insulin (odds ratio [OR] 0.86, 95% CI 0.79-0.95; p < 0.01), sodium-glucose cotransporter-2 (SGLT2) inhibitors (OR 0.68, 95% CI 0.58-0.79; p < 0.001), and glucagon-like peptide-1 (GLP-1) agonists (OR 0.37, 95% CI 0.31-0.44; p < 0.001). Black individuals were less likely than White individuals to be prescribed SGLT2 inhibitors (OR 0.50, 95% CI 0.39-0.65; p < 0.001) and GLP-1 agonists (OR 0.45, 95% CI 0.35-0.57; p < 0.001). Individuals in IMD quintile 5 were more likely than those in the other IMD quintiles to have annual testing for HbA1c, BP, eGFR, retinopathy, and neuropathy. Black individuals were less likely than White individuals to have annual testing for HbA1c (OR 0.89, 95% CI 0.79-0.99; p = 0.04) and retinopathy (OR 0.82, 95% CI 0.70-0.96; p = 0.011). Asian individuals were more likely than White individuals to have monitoring for HbA1c (OR 1.10, 95% CI 1.01-1.20; p = 0.023) and eGFR (OR 1.09, 95% CI 1.00-1.19; p = 0.048), but less likely for retinopathy (OR 0.88, 95% CI 0.79-0.97; p = 0.01) and neuropathy (OR 0.88, 95% CI 0.80-0.97; p = 0.01). The study is limited by the nature of being observational and defined using retrospectively collected data. Disparities in diabetes care may show regional variation, which was not part of this evaluation. Our findings suggest that disparity in glycaemic control, diabetes-related monitoring, and prescription of newer therapies remains a challenge in diabetes care. Both SES and ethnicity were important determinants of inequality. Disparities in glycaemic control and other areas of care may lead to higher rates of complications and adverse outcomes for some groups.

BACKGROUND: Primary care is computerized with routine data recorded at the point or care. Secondary use of these data includes: genetic study, epidemiology and clinical trials. However, there are relatively few international studies. OBJECTIVE: To identify the concepts that might predict readiness to collaborate in international research using routinely collected primary care data METHOD: Literature review and data gathering exercise, from international Primary Care Informatics working group workshops, and email modified Delphi exercise. RESULTS: To establish whether primary care data are fit for use in a collaborative study information is needed at the micro-, meso-, and macro-level. At the micro- or data level we need to use documented standards for interoperability, computerized records, to facilitate linkage of data. At the meso-level we need to understand the nature of the electronic patient record (EPR) and specific study requirements. At the macro-level: health system, social and cultural context constrain what data are available. The framework defines the information needed at the point of expression of interest, and joining a study. The initial assessment of readiness should be by self-assessment followed by an in depth appraisal more immediately prior to the start of the study. Finally, a sensitivity analysis should be conducted to test the robustness of the data model. CONCLUSIONS: The literature focuses on technical issues: interoperability, EPR and modeling; the workshops on socio-cultural and organizational. This framework will form the basis for developing a survey instrument of the initial assessment of readiness for collaboration in international research.

Aims To explore the prevalence and describe the clinical characteristics of people with type 2 diabetes with a similar cardiovascular (CV) profile to that of the LEADER trial participants in a primary care setting in England. Materials and methods In this cross-sectional analysis, using the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network database, we identified people with type 2 diabetes meeting the LEADER inclusion criteria. We identified people's CV risk factors using computerized medical records. Additionally, we assessed the prescription pattern of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in this cohort. Results Of 1 275 461 adults, we identified 84 394 with type 2 diabetes, of whom 14 000 (16.6%) met the LEADER inclusion criteria for established or high-risk CV disease (RCGP RSC-CVD group). The LEADER cohort was younger than the RCGP RSC-CVD group (64.2 vs 73.2 years), had higher mean glycated haemoglobin (71.6 vs 67.1 mmol/mol) and blood pressure (BP) values (systolic BP: 135.9 vs 132.9 mmHg; diastolic BP: 77.2 vs 72.7 mmHg), and a higher mean body mass index (32.5 vs 30.9 kg/m(2)). In the RCGP RSC-CVD group, only 1215 people (8.7%) had ever been prescribed a GLP-1RA and 760 (5.4%) had ever received liraglutide. Conclusions In a cohort of English general practice patients, one in six people with type 2 diabetes met the LEADER inclusion criteria, and less than one in 10 of these received liraglutide, a drug which has demonstrated CV benefits amongst others. There is scope to improve the outlook in people with type 2 diabetes and high CV risk through evidence-based use of specific GLP-1RAs.

The BNT162b2 mRNA (Pfizer-BioNTech) and ChAdOx1 nCoV-19 (Oxford-AstraZeneca) COVID-19 vaccines have shown high efficacy against disease in phase 3 clinical trials and are now being used in national vaccination programmes in the UK and several other countries. Studying the real-world effects of these vaccines is an urgent requirement. The aim of our study was to investigate the association between the mass roll-out of the first doses of these COVID-19 vaccines and hospital admissions for COVID-19. We did a prospective cohort study using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19-EAVE II-database comprising linked vaccination, primary care, real-time reverse transcription-PCR testing, and hospital admission patient records for 5·4 million people in Scotland (about 99% of the population) registered at 940 general practices. Individuals who had previously tested positive were excluded from the analysis. A time-dependent Cox model and Poisson regression models with inverse propensity weights were fitted to estimate effectiveness against COVID-19 hospital admission (defined as 1-adjusted rate ratio) following the first dose of vaccine. Between Dec 8, 2020, and Feb 22, 2021, a total of 1 331 993 people were vaccinated over the study period. The mean age of those vaccinated was 65·0 years (SD 16·2). The first dose of the BNT162b2 mRNA vaccine was associated with a vaccine effect of 91% (95% CI 85-94) for reduced COVID-19 hospital admission at 28-34 days post-vaccination. Vaccine effect at the same time interval for the ChAdOx1 vaccine was 88% (95% CI 75-94). Results of combined vaccine effects against hospital admission due to COVID-19 were similar when restricting the analysis to those aged 80 years and older (83%, 95% CI 72-89 at 28-34 days post-vaccination). Mass roll-out of the first doses of the BNT162b2 mRNA and ChAdOx1 vaccines was associated with substantial reductions in the risk of hospital admission due to COVID-19 in Scotland. There remains the possibility that some of the observed effects might have been due to residual confounding. UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK.

Background: Patients receiving cancer treatment often have one or more co-morbid conditions that are treated pharmacologically. Co-morbidities are recorded in clinical trials usually only at baseline. However, co-morbidities evolve and new ones emerge during cancer treatment. The interaction between multi-morbidity and cancer recovery is significant but poorly understood. Purpose: To investigate the effect of co-morbidities (e.g. cardiovascular and diabetes) and medications (e.g. statins, antihypertensives, metformin) on radiotherapy-related toxicity and long-term symptoms in order to identify potential risk factors. The possible protective effect of medications such as statins or antihypertensives in reducing radiotherapy-related toxicity will also be explored. Methods: Two datasets will be linked. 1) CHHiP (Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy for Prostate Cancer) randomised control trial. CHHiP contains pelvic symptoms and radiation-related toxicity reported by patients and clinicians. 2) GP (General Practice) data from RCGP RSC (Royal College of General Practitioners Research and Surveillance Centre). The GP records of CHHiP patients will be extracted, including cardiovascular co-morbidities, diabetes and prescription medications. Statistical analysis of the combined dataset will be performed in order to investigate the effect. Conclusions: Linking two sources of healthcare data is an exciting area of big healthcare data research. With limited data in clinical trials (not all clinical trials collect information on co-morbidities or medications) and limited lengths of follow-up, linking different sources of information is increasingly needed to investigate long-term outcomes. With increasing pressures to collect detailed information in clinical trials (e.g. co-morbidities, medications), linkage to routinely collected data offers the potential to support efficient conduct of clinical trials.

Aims To determine, in real-world primary care settings, the prevalence of, and risk factors for, retinopathy at Type 2 diabetes mellitus diagnosis and report cumulative incidence and progression of retinopathy seven years after diabetes diagnosis. Methods Retrospective cohort analysis of people with newly diagnosed Type 2 diabetes recorded by the Royal College of General Practitioners Research and Surveillance Centre (between 2005 and 2009, n=11,399). Outcomes included; retinopathy prevalence at diabetes diagnosis (baseline) and cumulative incidence or progression of retinopathy at seven years. Retinopathy prevalence was compared with the United Kingdom Prospective Diabetes Study (UKPDS-1998). Factors influencing retinopathy incidence and progression were analysed using logistic regression. Results Baseline retinopathy prevalence was 18% (n=2,048) versus 37% in UKPDS. At seven years, 11.6% (n=237) of those with baseline retinopathy had progression of retinopathy. In those without baseline retinopathy, 46.4% (n=4,337/9,351) developed retinopathy by seven years. Retinopathy development (OR: 1.05 [95%CI: 1.02–1.07] per mmol/mol increase) and progression (OR: 1.05 [1.04–1.06]) at seven years was associated with higher HbA1cat diabetes diagnosis. Obesity (OR: 0.88 [0.79–0.98]) and high socioeconomic status (OR: 0.63 [0.53–0.74]) were negatively associated with retinopathy development at seven years. Conclusions Baseline retinopathy prevalence has declined since UKPDS. Additionally, HbA1c at diabetes diagnosis remains important for retinopathy development and progression.

PURPOSE: Effective use of routine data to support integrated chronic disease management (CDM) and population health is dependent on underlying data quality (DQ) and, for cross system use of data, semantic interoperability. An ontological approach to DQ is a potential solution but research in this area is limited and fragmented. OBJECTIVE: Identify mechanisms, including ontologies, to manage DQ in integrated CDM and whether improved DQ will better measure health outcomes. METHODS: A realist review of English language studies (January 2001-March 2011) which addressed data quality, used ontology-based approaches and is relevant to CDM. RESULTS: We screened 245 papers, excluded 26 duplicates, 135 on abstract review and 31 on full-text review; leaving 61 papers for critical appraisal. Of the 33 papers that examined ontologies in chronic disease management, 13 defined data quality and 15 used ontologies for DQ. Most saw DQ as a multidimensional construct, the most used dimensions being completeness, accuracy, correctness, consistency and timeliness. The majority of studies reported tool design and development (80%), implementation (23%), and descriptive evaluations (15%). Ontological approaches were used to address semantic interoperability, decision support, flexibility of information management and integration/linkage, and complexity of information models. CONCLUSION: DQ lacks a consensus conceptual framework and definition. DQ and ontological research is relatively immature with little rigorous evaluation studies published. Ontology-based applications could support automated processes to address DQ and semantic interoperability in repositories of routinely collected data to deliver integrated CDM. We advocate moving to ontology-based design of information systems to enable more reliable use of routine data to measure health mechanisms and impacts.

Metadata is data that describes other data or resources. It has a defined number of named elements that convey meaning. Medical data are complex to process. For example, in the Primary Care Data Quality (PCDQ) renal programme, we need to collect over 300 variables because there are so many possible causes of renal disease. These variables are not just single columns of data--all are extracted as code plus date, while others are code-date-value. Metadata has the potential to improve the reliability of processing large datasets.

Background Chronic obstructive pulmonary disease (COPD) and type 2 diabetes (T2DM) are common comorbidities. COPD is a known risk factor for incident T2DM, however few studies have examined the relationship in reverse. The primary aim of this study was to compare the incidence of COPD in people with and without T2DM. Materials and methods We conducted a retrospective case-control study using a long-established English general practice network database (n = 894,646). We matched 29,217 cases of T2DM with controls, adjusting for age, gender, smoking status, BMI and social deprivation, to achieve 1:1 propensity matching and compared the rate of incident COPD over eight years of follow-up. We performed a secondary analysis to investigate the effect of insulin, metformin and sulphonylureas on COPD incidence. Results People with T2DM had a reduced risk of COPD compared to matched controls over the follow-up period (HR 0.89, 95%CI 0.79–0.93). 48.5% of those with T2DM were ex-smokers compared with 27.3% of those without T2DM. Active smoking rates were 20.4% and 23.7% respectively. Insulin, metformin and sulphonylureas were not associated with incident COPD. Conclusions People with T2DM are less likely to be diagnosed with COPD than matched controls. This may be due to positive lifestyle changes, such as smoking cessation in those with T2DM.

Objectives: To observe and analyse the range and nature of behaviour change techniques (BCTs) employed by audiologists during hearing-aid fitting consultations to encourage and enable hearing-aid use. Design: Non-participant observation and qualitative thematic analysis using the behaviour change technique taxonomy (version 1) (BCTTv1). Study sample: Ten consultations across five English NHS audiology departments. Results: Audiologists engage in behaviours to ensure the hearing-aid is fitted to prescription and is comfortable to wear. They provide information, equipment, and training in how to use a hearing-aid including changing batteries, cleaning, and maintenance. There is scope for audiologists to use additional BCTs: collaborating with patients to develop a behavioural plan for hearing-aid use that includes goal-setting, action-planning and problem-solving; involving significant others; providing information on the benefits of hearing-aid use or the consequences of non-use and giving advice about using prompts/cues for hearing-aid use. Conclusions: This observational study of audiologist behaviour in hearing-aid fitting consultations has identified opportunities to use additional behaviour change techniques that might encourage hearing-aid use. This information defines potential intervention targets for further research with the aim of improving hearing-aid use amongst adults with acquired hearing loss.

Background: Modelling is an important part of information science. Models are abstractions of reality. We use models in the following contexts: (1) to describe the data and information flows in clinical practice to information scientists, (2) to compare health systems and care pathways, (3) to understand how clinical cases are recorded in record systems and (4) to model health care business models. Asthma is an important condition associated with a substantial mortality and morbidity. However, there are difficulties in determining who has the condition, making both its incidence and prevalence uncertain. Objective: To demonstrate an approach for modelling complexity in health using asthma prevalence and incidence as an exemplar. Method: The four steps in our process are: 1. Drawing a rich picture, following Checkland’s soft systems methodology; 2. Constructing data flow diagrams (DFDs); 3. Creating Unified Modelling Language (UML) use case diagrams to describe the interaction of the key actors with the system; 4. Activity diagrams, either UML activity diagram or business process modelling notation diagram. Results: Our rich picture flagged the complexity of factors that might impact on asthma diagnosis. There was consensus that the principle issue was that there were undiagnosed and misdiagnosed cases as well as correctly diagnosed. Genetic predisposition to atopy; exposure to environmental triggers; impact of respiratory health on earnings or ability to attend education or participate in sport, charities, pressure groups and the pharmaceutical industry all increased the likelihood of a diagnosis of asthma. Stigma and some factors within the health system diminished the likelihood of a diagnosis. The DFDs and other elements focused on better case finding. Conclusions: This approach flagged the factors that might impact on the reported prevalence or incidence of asthma. The models suggested that applying selection criteria may improve the specificity of new or confirmed diagnosis.

Background It remains unclear to what extent reductions in urgent referrals for suspected cancer during the COVID-19 pandemic were the result of fewer patients attending primary care compared to GPs referring fewer patients. Methods Cohort study including electronic health records data from 8,192,069 patients from 663 English practices. Weekly consultation rates, cumulative consultations and referrals were calculated for 28 clinical features from the NICE suspected cancer guidelines. Clinical feature consultation rate ratios (CRR) and urgent referral rate ratios (RRR) compared time periods in 2020 with 2019. Findings Consultations for cancer clinical features decreased by 24.19% (95% CI: 24.04-24.34%) between 2019 and 2020, particularly in the 6-12 weeks following the first national lockdown. Urgent referrals for clinical features decreased by 10.47% (95% CI: 9.82-11.12%) between 2019 and 2020. Overall, once patients consulted with primary care, GPs urgently referred a similar or greater proportion of patients compared to previous years. Conclusion Due to the significant fall in patients consulting with clinical features of cancer there was a lower than expected number of urgent referrals in 2020. Sustained efforts should be made throughout the pandemic to encourage the public to consult their GP with cancer clinical features.

Understanding the physical and mental health needs of the population through evidence-based research is a priority for informing health policy. During the COVID-19 pandemic, population wellbeing dramatically dropped. The relationship between experiences of symptomatic illness episodes and health-related quality of life has been less documented. This study analysed the association between symptomatic COVID-19 illness and health-related quality of life. The analyses drew from a cross-sectional analysis of data from a national digital symptoms' surveillance survey conducted in the UK in 2020. We identified illness episodes using symptoms and test results data and we analysed validated health-related quality of life outcomes including health utility scores (indexed on a 0-1 cardinal scale) and visual analogue scale (VAS) scores (0-100 scale) generated by the EuroQoL's EQ-5D-5L measure. The econometric model controlled for respondents' demographic and socioeconomic characteristics, comorbidities, social isolation measures, and regional and time fixed effects. The results showed that the experience of common SARS-CoV-2 symptoms was significantly associated with poorer health-related quality of life across all EQ-5D-5L dimensions of mobility, self-care, usual activities, pain/discomfort and anxiety/depression, a decrement in utility score of - 0.13 and a decrement in the EQ-VAS score of - 15. The findings were robust to sensitivity analyses and restrictive test results-based definitions. This evidence-based study highlights the need for targeting of interventions and services towards those experiencing symptomatic episodes during future waves of the pandemic and helps to quantify the benefits of SARS-CoV-2 treatment in terms of health-related quality of life.

The 10g monofilament test is a simple method of detecting the presence of sensory neuropathy widely used by non-specialists; and included in pay-for-performance indicators for UK primary care. However, the association with increased mortality has not previously been explored. We performed a retrospective cohort analysis to determine if the presence of sensory neuropathy can be used as a predictor for increased risk of death. We used routinely recorded electronic data from 126 primary care centres across England, who participated in the Quality Improvement in Chronic Kidney Disease (QICKD) trial to follow a cohort of people with diabetes (N=35,502) over 30 months. The presence of sensory neuropathy was defined as present or absent based on routine 10g monofilament testing during 30 months prior to the observation period. The outcome measure was all-cause mortality. Known risk factors (age, gender, smoking status, co-morbidities, and HbA1c) were adjusted for using a multilevel logistic regression model. Monofilament testing was performed in 18,748 (52.2%) people during the baseline period. Abnormal sensation was identified in 1,548 (9.0%). Abnormal sensation was associated with an increased risk of mortality during the 30 month follow-up period: odds ratio 1.70 (95% confidence interval 1.41-2.06; p < 0.001). The association between mortality and sensory neuropathy was stronger than that with elevated HbA1c (OR 1.16; 95% CI 1.01-1.34; p = 0.037), and comparable to smoking, ischaemic heart disease, heart failure, and dyslipidaemia. Failure to monitor sensation using monofilament testing was also associated with an increased risk of mortality: OR 1.23 (95% CI 1.08-1.40; p = 0.002). The receiver operating characteristic (ROC) statistic for the model was 0.84. Sensory neuropathy is an important predictor of mortality in people with diabetes; and the monofilament test may have utility in primary care. People with abnormal sensation should be targeted for aggressive diabetes management.

Purpose The Translational Research and Patients safety in Europe (TRANSFoRm) project aims to integrate primary care with clinical research whilst improving patient safety. The TRANSFoRm International Research Readiness survey (TIRRE) aims to demonstrate data use through two linked data studies and by identifying clinical data repositories and genetic databases or disease registries prepared to participate in linked research. Method The TIRRE survey collects data at micro-, meso- and macro-levels of granularity; to fulfil data, study specific, business, geographical and readiness requirements of potential data providers for the TRANSFoRm demonstration studies. We used descriptive statistics to differentiate between demonstration-study compliant and non-compliant repositories. We only included surveys with >70% of questions answered in our final analysis, reporting the odds ratio (OR) of positive responses associated with a demonstration-study compliant data provider. Results We contacted 531 organisations within the Eurpean Union (EU). Two declined to supply information; 56 made a valid response and a further 26 made a partial response. Of the 56 valid responses, 29 were databases of primary care data, 12 were genetic databases and 15 were cancer registries. The demonstration compliant primary care sites made 2098 positive responses compared with 268 in non-use-case compliant data sources [OR: 4.59, 95% confidence interval (CI): 3.93–5.35, p < 0.008]; for genetic databases: 380:44 (OR: 6.13, 95% CI: 4.25–8.85, p < 0.008) and cancer registries: 553:44 (OR: 5.87, 95% CI: 4.13–8.34, p < 0.008).Conclusions TIRRE comprehensively assesses the preparedness of data repositories to participate in specific research projects. Multiple contacts about hypothetical participation in research identified few potential sites.

Objectives: To investigate the effect of providing patients online access to their electronic health record (EHR) and linked transactional services on the provision, quality and safety of healthcare. The objectives are also to identify and understand: barriers and facilitators for providing online access to their records and services for primary care workers; and their association with organisational/IT system issues. Setting: Primary care. Participants: A total of 143 studies were included. 17 were experimental in design and subject to risk of bias assessment, which is reported in a separate paper. Detailed inclusion and exclusion criteria have also been published elsewhere in the protocol. Primary and secondary outcome measures: Our primary outcome measure was change in quality or safety as a result of implementation or utilisation of online records/transactional services. Results: No studies reported changes in health outcomes; though eight detected medication errors and seven reported improved uptake of preventative care. Professional concerns over privacy were reported in 14 studies. 18 studies reported concern over potential increased workload; with some showing an increase workload in email or online messaging; telephone contact remaining unchanged, and face-to face contact staying the same or falling. Owing to heterogeneity in reporting overall workload change was hard to predict. 10 studies reported how online access offered convenience, primarily for more advantaged patients, who were largely highly satisfied with the process when clinician responses were prompt. Conclusions: Patient online access and services offer increased convenience and satisfaction. However, professionals were concerned about impact on workload and risk to privacy. Studies correcting medication errors may improve patient safety. There may need to be a redesign of the business process to engage health professionals in online access and of the EHR to make it friendlier and provide equity of access to a wider group of patients.

Anonymised primary care electronic health records (EHR) have been available for research in the UK for at least two decades. The time has come for a rethink in how we coordinate the sharing of data for research, in a way that provides clear benefits for patients and practices as well as researchers. Up until now, sharing data for research provides long-term benefits for the public, patients, and practitioners as a result of the implementation of these research findings. While these benefits are clearly in the public interest, our current approach provides few immediate benefits.

Background Diabetes confers a two times excess risk of cardiovascular disease, yet predicting individual risk remains challenging. The effect of total microvascular disease burden on cardiovascular disease risk among individuals with diabetes is unknown. Methods A population-based cohort of patients with type 2 diabetes from the UK Clinical Practice Research Datalink was studied (n=49 027). We used multivariable Cox models to estimate hazard ratios (HRs) for the primary outcome (the time to first major cardiovascular event, which was a composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal ischaemic stroke) associated with cumulative burden of retinopathy, nephropathy, and peripheral neuropathy among individuals with no history of cardiovascular disease at baseline.Findings During a median follow-up of 5·5 years, 2822 (5·8%) individuals experienced a primary outcome. After adjustment for established risk factors, significant associations were observed for the primary outcome individually for retinopathy (HR 1·39, 95% CI 1·09–1·76), peripheral neuropathy (1·40, 1·19–1·66), and nephropathy (1·35, 1·15–1·58). For individuals with one, two, or three microvascular disease states versus none, the multivariable-adjusted HRs for the primary outcome were 1·32 (95% CI 1·16–1·50), 1·62 (1·42–1·85), and 1·99 (1·70–2·34), respectively. For the primary outcome, measures of risk discrimination showed significant improvement when microvascular disease burden was added to models. In the overall cohort, the net reclassification index for USA and UK guideline risk strata were 0·036 (95% CI 0·017–0·055, p

Cities are constantly evolving and so are the living conditions within and between them. Rapid urbanization and the ever-growing need for housing have turned large areas of many cities into concrete landscapes that lack greenery. Green infrastructure can support human health, provide socio-economic and environmental benefits, and bring color to an otherwise grey urban landscape. Sometimes, benefits come with downsides in relation to its impact on air quality and human health, requiring suitable data and guidelines to implement effective greening strategies. Air pollution and human health, as well as green infrastructure and human health, are often studied together. Linking green infrastructure with air quality and human health together is a unique aspect of this article. A holistic understanding of these links is key to enabling policymakers and urban planners to make informed decisions. By critically evaluating the link between green infrastructure and human health via air pollution mitigation, we also discuss if our existing understanding of such interventions is enabling their uptake in practice. Both the natural science and epidemiology approach the topic of green infrastructure and human health very differently. The pathways linking health benefits to pollution reduction by urban vegetation remain unclear and that the mode of green infrastructure deployment is critical to avoid unintended consequences. Strategic deployment of green infrastructure may reduce downwind pollution exposure. However, the development of bespoke design guidelines is vital to promote and optimize greening benefits and measuring green infrastructure’s socio-economic and health benefits are key for their uptake. Greening cities to mitigate pollution effects is on the rise and these needs to be matched by scientific evidence and appropriate guidelines. We conclude that urban vegetation can facilitate broad health benefits, but there is little empirical evidence linking these benefits to air pollution reduction by urban vegetation, and appreciable efforts are needed to establish the underlying policies, design and engineering guidelines governing its deployment.

Irritable bowel syndrome is a common condition in general practice. It occurs in 10 to 20% of the population, but less than half seek medical assistance with the complaint.

Chronic kidney disease (CKD) is a relatively recently recognised condition. People with CKD are much more likely to suffer from cardiovascular events than progress to established renal failure. Controlling systolic blood pressure should slow the progression of disease and reduce mortality and morbidity. However, no systematic review has been conducted to explore the effectiveness of quality-improvement interventions to lower blood pressure in people with CKD.

Background: Hepatitis A outbreaks in the United Kingdom are uncommon. Most people develop mild to moderate symptoms that resolve, without sequelae, within months. However, in high-risk groups, including those with underlying chronic liver disease (CLD), hepatitis A infection can be severe, with a higher risk of mortality and morbidity. The Health Security Agency and the National Institute of Health and Care Excellence recommend preexposure hepatitis A vaccination given in 2 doses to people with CLD, regardless of its cause. There are currently no published reports of vaccination coverage for people with CLD in England or internationally.Objective: This study aims to describe hepatitis A vaccination coverage in adults with CLD in a UK primary care setting and compare liver disease etiology, sociodemographic characteristics, and comorbidities in people who are and are not exposed to the hepatitis A vaccine.Methods: We will conduct a retrospective cohort study with data from the Primary Care Sentinel Cohort of the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub database, which is nationally representative of the English population. We will include people aged 18 years and older who have been registered in general practices in the Research and Surveillance Centre network and have a record of CLD between January 1, 2012, and December 31, 2022, including those with alcohol-related liver disease, chronic hepatitis B, chronic hepatitis C, nonalcohol fatty liver disease, Wilson disease, hemochromatosis, and autoimmune hepatitis. We will carefully curate variables using the Systematized Nomenclature of Medicine Clinical Terms. We will report the sociodemographic characteristics of those who are vaccinated. These include age, gender, ethnicity, population density, region, socioeconomic status (measured using the index of multiple deprivation), obesity, alcohol consumption, and smoking. Hepatitis A vaccination coverage for 1 and 2 doses will be calculated using an estimate of the CLD population as the denominator. We will analyze the baseline characteristics using descriptive statistics, including measures of dispersion. Pairwise comparisons of case-mix characteristics, comorbidities, and complications will be reported according to vaccination status. A multistate survival model will be fitted to estimate the transition probabilities among four states: (1) diagnosed with CLD, (2) first dose of hepatitis A vaccination, (3) second dose of hepatitis A vaccination, and (4) death. This will identify any potential disparities in how people with CLD get vaccinated. Results: The Research and Surveillance Centre population comprises over 8 million people. The reported incidence of CLD is 20.7 cases per 100,000. International estimates of hepatitis A vaccine coverage vary between 10% and 50% in this group. Conclusions: This study will describe the uptake of the hepatitis A vaccine in people with CLD and report any disparities or differences in the characteristics of the vaccinated population.

BACKGROUND: Generally benefits and risks of vaccines can be determined from studies carried out as part of regulatory compliance, followed by surveillance of routine data; however there are some rarer and more long term events that require new methods. Big data generated by increasingly affordable personalised computing, and from pervasive computing devices is rapidly growing and low cost, high volume, cloud computing makes the processing of these data inexpensive. OBJECTIVE: To describe how big data and related analytical methods might be applied to assess the benefits and risks of vaccines. METHOD: We reviewed the literature on the use of big data to improve health, applied to generic vaccine use cases, that illustrate benefits and risks of vaccination. We defined a use case as the interaction between a user and an information system to achieve a goal. We used flu vaccination and pre-school childhood immunisation as exemplars. RESULTS: We reviewed three big data use cases relevant to assessing vaccine benefits and risks: (i) Big data processing using crowdsourcing, distributed big data processing, and predictive analytics, (ii) Data integration from heterogeneous big data sources, e.g. the increasing range of devices in the "internet of things", and (iii) Real-time monitoring for the direct monitoring of epidemics as well as vaccine effects via social media and other data sources. CONCLUSIONS: Big data raises new ethical dilemmas, though its analysis methods can bring complementary real-time capabilities for monitoring epidemics and assessing vaccine benefit-risk balance.

Background: There are conflicting views in the literature as to whether vitamin D2 and vitamin D3 are equally effective in increasing and maintaining serum concentrations of 25-hydroxyvitamin D [25(OH)D], particularly at lower doses of vitamin D. Objective: We aimed to investigate whether vitamin D2 or vitamin D3 fortified in juice or food, at a relatively low dose of 15 μg/d, was effective in increasing serum total 25(OH)D and to compare their respective efficacy in South Asian and white European women over the winter months within the setting of a large randomized controlled trial. Design: A randomized, double-blind, placebo-controlled food-fortification trial was conducted in healthy South Asian and white European women aged 20–64 y (n = 335; Surrey, United Kingdom) who consumed placebo, juice supplemented with 15 μg vitamin D2, biscuit supplemented with 15 μg vitamin D2, juice supplemented with 15 μg vitamin D3, or biscuit supplemented with 15 μg vitamin D3 daily for 12 wk. Serum 25(OH)D was measured by liquid chromatography–tandem mass spectrometry at baseline and at weeks 6 and 12 of the study. Results: Postintervention in the 2 ethnic groups combined, both the vitamin D3 biscuit and the vitamin D3 juice groups showed a significantly greater absolute incremental change (Δ) in total 25(OH)D when compared with the vitamin D2 biscuit group [Δ (95% CI): 15.3 nmol/L (7.4, 23.3 nmol/L) (P < 0.0003) and 16.0 nmol/L (8.0, 23.9 nmol/L) ( P < 0.0001)], the vitamin D2 juice group [Δ (95% CI): 16.3 nmol/L (8.4, 24.2 nmol/L) (P < 0.0001) and 16.9 nmol/L (9.0, 24.8 nmol/L) (P < 0.0001)], and the placebo group [Δ (95% CI): 42.3 nmol/L (34.4, 50.2 nmol/L) (P < 0.0001) and 42.9 nmol/L (35.0, 50.8 nmol/L) (P < 0.0002)]. Conclusions: With the use of a daily dose of vitamin D relevant to public health recommendations (15 μg) and in vehicles relevant to food-fortification strategies, vitamin D3 was more effective than vitamin D2 in increasing serum 25(OH)D in the wintertime. Vitamin D3 may therefore be a preferential form to optimize vitamin D status within the general population. This trial was registered at www.controlled-trials.com as ISRCTN23421591.

Physician associates (PAs) are a new type of healthcare professional to the United Kingdom; however, they are well established in the United States (where they are known as physician assistants). PAs are viewed as one potential solution to the current medical workforce doctor shortage. This study investigated the deployment of PAs within secondary care teams in England, through the use of a cross-sectional electronic, self-report survey. The findings from 14 questions are presented. Sixty-three PAs working in a range of specialties responded. A variety of work settings were reported, most frequently inpatient wards, with work generally taking place during weekdays. Both direct and non-direct patient care activities were reported, with the type of work undertaken varying at times, depending on the presence or absence of other healthcare professionals. PAs reported working within a variety of secondary care team staffing permutations, with the majority of these being interprofessional. Line management was largely provided by consultants; however day-to-day supervision varied, often relating to different work settings. A wide variation in ongoing supervision was also reported. Further research is required to understand the nature of PAs’ contribution to collaborative care within secondary care teams in England.

Aim The use of glucagon-like peptide-1 (GLP-1) agonists in type 2 diabetes is increasing. We present a description of their current use and prescribing trends in UK primary care and compare the characteristics of people prescribed GLP-1 agonists with phase 3 trial populations.

Prescribing errors are common and costly. Technology should enable safer prescribing. The two main current methods of doing so are computer initiated clinical support software (CDSS) and the user initiated information retrieval (IR) systems. However, despite the near universal availability of computerised prescribing support in the UK, errors continue.

There is growing interest in preconception health as a crucial period for influencing not only pregnancy outcomes, but also future maternal and child health, and prevention of long-term medical conditions. Successive national and international policy documents emphasise the need to improve preconception health, but resources and action have not followed through with these goals. We argue for a dual intervention strategy at both the public health level (eg, by improving the food environment) and at the individual level (eg, by better identification of those planning a pregnancy who would benefit from support to optimise health before conception) in order to raise awareness of preconception health and to normalise the notion of planning and preparing for pregnancy. Existing strategies that target common risks factors, such as obesity and smoking, should recognise the preconception period as one that offers special opportunity for intervention, based on evidence from life-course epidemiology, developmental (embryo) programming around the time of conception, and maternal motivation. To describe and monitor preconception health in England, we propose an annual report card using metrics from multiple routine data sources. Such a report card should serve to hold governments and other relevant agencies to account for delivering interventions to improve preconception health.

Diarrheal disease, which affects 1 in 4 people in the United Kingdom annually, is the most common cause of outbreaks in community and health care settings. Traditional surveillance methods tend to detect point-source outbreaks of diarrhea and vomiting; they are less effective at identifying low-level and intermittent food supply contamination. Furthermore, it can take up to 9 weeks for infections to be confirmed, reducing slow-burn outbreak recognition, potentially impacting hundreds or thousands of people over wide geographical areas. There is a need to address fundamental problems in traditional diarrheal disease surveillance because of underreporting and subsequent unconfirmed infection by patients and general practitioners (GPs); varying submission practices and selective testing of samples in laboratories; limitations in traditional microbiological diagnostics, meaning that the timeliness of sample testing and etiology of most cases remains unknown; and poorly integrated human and animal surveillance systems, meaning that identification of zoonoses is delayed or missed. This study aims to detect anomalous patterns in the incidence of gastrointestinal disease in the (human) community; to target sampling; to test traditional diagnostic methods against rapid, modern, and sensitive molecular and genomic microbiology methods that identify and characterize responsible pathogens rapidly and more completely; and to determine the cost-effectiveness of rapid, modern, sensitive molecular and genomic microbiology methods. Syndromic surveillance will be used to aid identification of anomalous patterns in microbiological events based on temporal associations, demographic similarities among patients and animals, and changes in trends in acute gastroenteritis cases using a point process statistical model. Stool samples will be obtained from patients' consulting GPs, to improve the timeliness of cluster detection and characterize the pathogens responsible, allowing health protection professionals to investigate and control outbreaks quickly, limiting their size and impact. The cost-effectiveness of the proposed system will be examined using formal cost-utility analysis to inform decisions on national implementation. The project commenced on April 1, 2013. Favorable approval was obtained from the Research Ethics Committee on June 15, 2015, and the first patient was recruited on October 13, 2015, with 1407 patients recruited and samples processed using traditional laboratory techniques as of March 2017. The overall aim of this study is to create a new One Health paradigm for detecting and investigating diarrhea and vomiting in the community in near-real time, shifting from passive human surveillance and management of laboratory-confirmed infection toward an integrated, interdisciplinary enhanced surveillance system including management of people with symptoms. DERR1-10.2196/13941.

Introduction: Acute kidney injury (AKI) is characterised by a rapid deterioration in kidney function, and can be identified by examining the rate of change in a patient’s estimated glomerular filtration rate (eGFR). Due to the potentially irreversible nature of the damage AKI episodes cause to renal function, their detection can play a significant role in predicting a kidney’s effectiveness. Although algorithms for the detection of AKI are available for patients under constant monitoring, e.g. inpatients, their applicability to primary care settings is less clear as patients’ eGFR often contains large lapses in time between measurements. We therefore present two alternative automated approaches for detecting AKI: using the novel Surrey AKI detection algorithm (SAKIDA) (Figure a) and as the outlier points when using Gaussian process regression (GPR) (Figure b).

Although routine healthcare data are not collected for research, they are increasingly used in epidemiology and are key real-world evidence for improving healthcare. This study presents a method to identify prostate cancer cases from a large English primary care database. 19,619 (1.3%) men had a code for prostate cancer diagnosis. Codes for medium and high Gleason grading enabled identification of additional 94 (0.5%) cases. Many studies do not report codes used to identify patients, and if published, the lists of codes differ from study to study. This can lead to poor research reproducibility and hinder validation. This work demonstrates that carefully developed comprehensive lists of clinical codes can be used to identify prostate cancer; and that approaches that do not solely rely on clinical codes such as ontologies or data linkage should also be considered.

The introduction of point-of-care tests (POCTs) has presented new opportunities for the management of patients presenting to healthcare providers with acute respiratory symptoms. This Perspective article is based on the experiences of national infection teams/those managing acute respiratory infections across the United Kingdom in terms of the challenges and opportunities that this may present for public health. This Perspective article was conceived and written pre-coronavirus disease (COVID-19), however the principles we outline here for influenza can also be translated to COVID-19 and some key points are made throughout the article. The greatest challenge for intergrating POCTs into non-traditional environments is the capture of data and samples for surveillance purposes which provides information for public health action. However, POCTs together with measures outlined in this article, offer a new paradigm for the management and public health surveillance of patients with influenza.

Objective : Internationally, primary care practice had to transform in response to the COVID pandemic. Informatics issues included access, privacy, and security, as well as patient concerns of equity, safety, quality, and trust. This paper describes progress and lessons learned. Methods : IMIA Primary Care Informatics Working Group members from Australia, Canada, United Kingdom and United States developed a standardised template for collection of information. The template guided a rapid literature review. We also included experiential learning from primary care and public health perspectives. Results : All countries responded rapidly. Common themes included rapid reductions then transformation to virtual visits, pausing of non-COVID related informatics projects, all against a background of non-standardized digital development and disparate territory or state regulations and guidance. Common barriers in these four and in less-resourced countries included disparities in internet access and availability including bandwidth limitations when internet access was available, initial lack of coding standards, and fears of primary care clinicians that patients were delaying care despite the availability of televisits. Conclusions : Primary care clinicians were able to respond to the COVID crisis through telehealth and electronic record enabled change. However, the lack of coordinated national strategies and regulation, assurance of financial viability, and working in silos remained limitations. The potential for primary care informatics to transform current practice was highlighted. More research is needed to confirm preliminary observations and trends noted.

Understanding the connection between physical and mental health with evidence-based research is important to inform and support targeted screening and early treatment. The objective of this study was to document the co-occurrence of physical and mental health conditions during and after the experience of symptomatic SARS-CoV-2 illness episodes. Drawing from a national symptoms' surveillance survey conducted in the UK in 2020, this study shows that individuals with symptomatic forms of SARS-CoV-2 (identified by anosmia with either fever, breathlessness or cough) presented significantly higher odds of experiencing moderate and severe anxiety (2.41, CI 2.01-2.90) and depression (3.64, CI 3.06-4.32). Respondents who recovered from physical SARS-CoV-2 symptoms also experienced higher odds of anxiety and depression in comparison to respondents who never experienced symptoms. The findings are robust to alternative estimation models that compare individuals with the same socioeconomic and demographic characteristics and who experienced the same local and contextual factors such as mobility and social restrictions. The findings have important implications for the screening and detection of mental health disorders in primary care settings. They also suggest the need to design and test interventions to address mental health during and after physical illness episodes.

We have used routinely collected clinical data in epidemiological and quality improvement research for over 10 years. We extract, pseudonymise and link data from heterogeneous distributed databases; inevitably encountering errors and problems.

Background: Physician associates, known internationally as physician assistants, are a mid-level practitioner, well established in the United States of America but new to the United Kingdom. A small number work in primary care under the supervision of general practitioners, where they most commonly see patients requesting same day appointments for new problems. As an adjunct to larger study, we investigated the quality of the patient consultation of physician associates in comparison to that of general practitioners. Method: We conducted a comparative observational study using video recordings of consultations by volunteer physician associates and general practitioners with consenting patients in single surgery sessions. Recordings were assessed by experienced general practitioners, blinded to the type of the consulting practitioner, using the Leicester Assessment Package. Assessors were asked to comment on the safety of the recorded consultations and to attempt to identify the type of practitioner. Ratings were compared across practitioner type, alongside the number of presenting complaints discussed in each consultation and the number of these which were acute, minor, or regarding a chronic condition. Results: We assessed 62 consultations (41 general practitioner and 21 physician associates) from five general practitioners and four physician associates. All consultations were assessed as safe; but general practitioners were rated higher than PAs in all elements of consultation. The general practitioners were more likely than physician associates to see people with multiple presenting complaints (p

Background: Living in a conurbation, urban, or rural environment is an important determinant of health. For example, conurbation and rural living is associated with increased respiratory and allergic conditions, whereas a farm or rural upbringing has been shown to be a protective factor against this. Objective: The objective of the study was to assess differences in general practice presentations of allergic and infectious disease in those exposed to conurbation or urban living compared with rural environments. Methods: The population was a nationally representative sample of 175 English general practices covering a population of over 1.6 million patients registered with sentinel network general practices. General practice presentation rates per 100,000 population were reported for allergic rhinitis, asthma, and infectious conditions grouped into upper and lower respiratory tract infections, urinary tract infection, and acute gastroenteritis by the UK Office for National Statistics urban-rural category. We used multivariate logistic regression adjusting for age, sex, ethnicity, deprivation, comorbidities, and smoking status, reporting odds ratios (ORs) with 95% CIs. Results: For allergic rhinitis, the OR was 1.13 (95% CI 1.04-1.23; P=.003) for urban and 1.29 (95% CI 1.19-1.41; P

Background In September 2015, the United Kingdom became the first country to introduce the multicomponent group B meningococcal vaccine (4CMenB) into a national infant immunisation programme. In early clinical trials 51–61% of infants developed a fever when 4CMenB was administered with other routine vaccines. Whilst administration of prophylactic paracetamol is advised, up to 3% of parents may seek medical advice for fever following vaccination. We used research-level general practitioner consultations to identify any increase in attendances for all-cause fever in vaccine-eligible infants following 4CMenB introduction in England. Methods Consultations for infant all-cause fever in the year following the vaccine introduction were identified from The Phoenix Partnership (TPP) ResearchOne general practice database using Read (CTV3) codes. Average daily consultation rates and incidence rate ratios (IRRs) were calculated for vaccine-eligible age groups and compared to the two years preceding vaccine introduction. The difference between pre- and post-vaccine all-cause fever consultations was estimated. Results All-cause fever consultations in vaccine-eligible 7–10 week olds were 1.6-fold higher (IRR, 1.58; 95% CI, 1.22–2.05) compared to the two previous years and 1.5-fold higher (IRR 1.47; 95% CI, 1.17–1.86) in 15–18 week-olds. There were no significant differences in 0–6 or 11–14 week-olds. Applying the difference between pre- and post-vaccine consultation rates to the 4CMenB vaccine-eligible age groups across England estimated 1825 additional fever consultations in the year following 4CMenB introduction. Conclusions We found a small but significant difference in all-cause fever consultation rates in vaccine-eligible infants who would have received 4CMenB with other vaccines.

Many practices in the UK have computerised information dating back to the 1990s. These health records provide contemporaneous collected longitudinal data for analysis of health trends and their management in primary care over time.

The Primary Care Data Quality programme (PCDQ) is a quality-improvement programme which processes routinely collected general practice computer data. Patient data collected from a wide range of different brands of clinical computer systems are aggregated, processed, and fed back to practices in an educational context to improve the quality of care. Process modelling is a well-established approach used to gain understanding and systematic appraisal, and identify areas of improvement of a business process. Unified modelling language (UML) is a general purpose modelling technique used for this purpose. We used UML to appraise the PCDQ process to see if the efficiency and predictability of the process could be improved. Activity analysis and thinking-aloud sessions were used to collect data to generate UML diagrams. The UML model highlighted the sequential nature of the current process as a barrier for efficiency gains. It also identified the uneven distribution of process controls, lack of symmetric communication channels, critical dependencies among processing stages, and failure to implement all the lessons learned in the piloting phase. It also suggested that improved structured reporting at each stage-especially from the pilot phase, parallel processing of data and correctly positioned process controls-should improve the efficiency and predictability of research projects. Process modelling provided a rational basis for the critical appraisal of a clinical data processing system; its potential maybe underutilized within health care. © 2007 Informa UK Ltd All rights reserved.

Background: Physician Associates are new to English general practice and set to expand in numbers. Objective: To investigate the patients’ perspective on consulting with PAs in general practice. Design: A qualitative study, using semi structured interviews, with thematic analysis. Setting and participants: Thirty volunteer patients of 430 who had consulted PAs for a same day appointment and had returned a satisfaction survey, in six general practices employing physician associates in England. Findings: Some participants only consulted once with a physician associate and others more frequently. The conditions consulted for ranged from minor illnesses to those requiring immediate hospital admission. Understanding the role of the physician associate varied from: certain and correct, to uncertain, to certain and incorrect, where the patient believed the physician associate to be a doctor. Most, but not all, reported positive experiences and outcomes of their consultation, with some choosing to consult the physician. Those with negative experiences described problems when the limits of the role was reached, requiring additional GP consultations or prescription delay. Trust and confidence in the physician associate was derived from trust in the NHS, the general practice and the individual physician associate. Willingness to consult a physician associate was contingent on the patient’s assessment of the severity or complexity of the problem and the desire for provider continuity. Conclusion: Patients saw PAs as an appropriate general practitioner substitute. Patients’ experience could inform delivery redesign.

Background: The burden of chronic disease is increasing, and research and quality improvement will be less effective if case finding strategies are suboptimal. Objective: To describe an ontology-driven approach to case finding in chronic disease and how this approach can be used to create a data dictionary and make the codes used in case finding transparent. Method: A five-step process: (1) identifying a reference coding system or terminology; (2) using an ontology-driven approach to identify cases; (3) developing metadata that can be used to identify the extracted data; (4) mapping the extracted data to the reference terminology; and (5) creating the data dictionary. Results: Hypertension is presented as an exemplar. A patient with hypertension can be represented by a range of codes including diagnostic, history and administrative. Metadata can link the coding system and data extraction queries to the correct data mapping and translation tool, which then maps it to the equivalent code in the reference terminology. The code extracted, the term, its domain and subdomain, and the name of the data extraction query can then be automatically grouped and published online as a readily searchable data dictionary. An exemplar online is: www.clininf.eu/qickd-datadictionary. html Conclusion: Adopting an ontology-driven approach to case finding could improve the quality of disease registers and of research based on routine data. It would offer considerable advantages over using limited datasets to define cases. This approach should be considered by those involved in research and quality improvement projects which utilise routine data.

Introduction: One of the key challenges in understanding CKD progression is its multifaceted aetiology. This is evident as it is commonly observed that hypertension, heart disease and diabetes are common co-morbidities of CKD. In other words, the existence of co-morbidities can potentially alter the risk of CKD progression, e.g. from stage 3 to 5. Unfortunately, “flat” risk models such as logistic regression, e.g. as implemented by the QKidney score and many similar risk models, are not designed to extract the rich structure induced by a multitude of co-morbidities, the state of which are often captured in routinely collected patient data.

Background The Platform Randomised trial of INterventions against COVID-19 In older peoPLE (PRINCIPLE) has provided in-pandemic evidence that azithromycin and doxycycline were not beneficial in the early primary care management of coronavirus 2019 disease (COVID-19). Aim To explore the extent of in-pandemic azithromycin and doxycycline use, and the scope for trial findings impacting on practice. Design & setting Crude rates of prescribing and respiratory tract infections (RTI) in 2020 were compared with 2019, using the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC). Method Negative binomial models were used to compare azithromycin and doxycycline prescribing, lower respiratory tract infections (LRTI), upper respiratory tract infections (URTI), and influenza-like illness (ILI) in 2020 with 2019; reporting incident rate ratios (IRR) between years, and 95% confidence intervals (95% CI). Results Azithromycin prescriptions increased 7% in 2020 compared with 2019, whereas doxycycline decreased by 7%. Concurrently, LRTI and URTI incidence fell by over half (58.3% and 54.4%, respectively) while ILI rose slightly (6.4%). The overall percentage of RTI-prescribed azithromycin rose from 0.51% in 2019 to 0.72% in 2020 (risk difference 0.214%; 95% CI = 0.211 to 0.217); doxycycline rose from 11.86% in 2019 to 15.79% in 2020 (risk difference 3.93%; 95% CI = 3.73 to 4.14). The adjusted IRR showed azithromycin prescribing was 22% higher in 2020 (IRR = 1.22; 95% CI = 1.19 to 1.26; P

Background: Innovators have piloted improvements in communication, changed patterns of practice and patient empowerment from online access to electronic health records (EHR). International studies of online services, such as prescription ordering, online appointment booking and secure communications with primary care, show good uptake of email consultations, accessing test results and booking appointments; when technologies and business process are in place. Online access and transactional services are due to be rolled out across England by 2015; this review seeks to explore the impact of online access to health records and other online services on the quality and safety of primary health care. Objective: To assess the factors that may affect the provision of online patient access to their EHR and transactional services, and the impact of such access on the quality and safety of health care. Method: Two reviewers independently searched 11 international databases during the period 1999-2012. A range of papers including descriptive studies using qualitative or quantitative methods, hypothesis-testing studies and systematic reviews were included. A detailed eligibility criterion will be used to shape study inclusion. A team of experts will review these papers for eligibility, extract data using a customised extraction form and use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) instrument to determine the quality of the evidence and the strengths of any recommendation. Data will then be descriptively summarised and thematically synthesised. Where feasible, we will perform a quantitative meta-analysis. Prospero (International Prospective Register of Systematic Reviews) registration number: crd42012003091.

Introduction frailty is common in older adults and is associated with increased health and social care use. Longitudinal information is needed on population-level incidence, prevalence and frailty progression to plan services to meet future population needs. Methods retrospective open cohort study using electronic health records of adults aged ≥50 from primary care in England, 2006–2017. Frailty was calculated annually using the electronic Frailty Index (eFI). Multistate models estimated transition rates between each frailty category, adjusting for sociodemographic characteristics. Prevalence overall for each eFI category (fit, mild, moderate and severe) was calculated. Results the cohort included 2,171,497 patients and 15,514,734 person-years. Frailty prevalence increased from 26.5 (2006) to 38.9% (2017). The average age of frailty onset was 69; however, 10.8% of people aged 50–64 were already frail in 2006. Estimated transitions from fit to any level of frailty were 48/1,000 person-years aged 50–64, 130/1,000 person-years aged 65–74, 214/1,000 person-years aged 75–84 and 380/1,000 person-years aged ≥ 85. Transitions were independently associated with older age, higher deprivation, female sex, Asian ethnicity and urban dwelling. Mean time spent in each frailty category decreased with age, with the longest period spent in severe frailty at all ages. Conclusions frailty is prevalent in adults aged ≥50 and time spent in successive frailty states is longer as frailty progresses, resulting in extended healthcare burden. Larger population numbers and fewer transitions in adults aged 50–64 present an opportunity for earlier identification and intervention. A large increase in frailty over 12 years highlights the urgency of informed service planning in ageing populations.

Author summary Influenza, the flu, is a highly infectious respiratory disease that can cause serious health complications. Characterised by seasonal outbreaks, a key challenge for policy-makers is implementing measures to successfully lessen the public health burden on an annual basis. Seasonal influenza vaccine programmes are an established method to deliver cost-effective prevention against influenza and its complications. Transmission models have been a fundamental component of vaccine programme analysis, informing the efficient use of limited resources. However, these models generally treat each influenza season and each strain circulating within that season in isolation. By developing a mathematical model explicitly including multiple immunity propagation mechanisms, then fit to influenza-related vaccine and epidemiological data from England via statistical methods, we sought to quantify the extent that epidemiological events in the previous influenza season alter susceptibility at the onset of the following season. The findings suggest that susceptibility in the next season to a given influenza strain type is modulated to the greatest extent through natural infection by that strain type in the current season. Residual vaccine immunity has a lesser role. Prospectively, the adoption of influenza transmission modelling frameworks with immunity propagation would provide a comprehensive manner to assess the impact of seasonal vaccination programmes. Seasonal influenza poses serious problems for global public health, being a significant contributor to morbidity and mortality. In England, there has been a long-standing national vaccination programme, with vaccination of at-risk groups and children offering partial protection against infection. Transmission models have been a fundamental component of analysis, informing the efficient use of limited resources. However, these models generally treat each season and each strain circulating within that season in isolation. Here, we amalgamate multiple data sources to calibrate a susceptible-latent-infected-recovered type transmission model for seasonal influenza, incorporating the four main strains and mechanisms linking prior season epidemiological outcomes to immunity at the beginning of the following season. Data pertaining to nine influenza seasons, starting with the 2009/10 season, informed our estimates for epidemiological processes, virological sample positivity, vaccine uptake and efficacy attributes, and general practitioner influenza-like-illness consultations as reported by the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC). We performed parameter inference via approximate Bayesian computation to assess strain transmissibility, dependence of present season influenza immunity on prior protection, and variability in the influenza case ascertainment across seasons. This produced reasonable agreement between model and data on the annual strain composition. Parameter fits indicated that the propagation of immunity from one season to the next is weaker if vaccine derived, compared to natural immunity from infection. Projecting the dynamics forward in time suggests that while historic immunity plays an important role in determining annual strain composition, the variability in vaccine efficacy hampers our ability to make long-term predictions.

Background: Most people with dementia do not receive timely diagnosis, preventing them from making informed plans about their future and accessing services. Many countries have a policy to increase timely diagnosis, but trials aimed at changing general practitioner (GP) practice have been unsuccessful. We aimed to assess whether a GP’s personal letter, with an evidence-based leaflet about overcoming barriers to accessing help for memory problems—aimed at empowering patients and families—increases timely dementia diagnosis and patient presentation to general practice. Methods and finding: Multicentre, cluster-randomised controlled trial with raters masked to an online computer-generated randomisation system assessing 1 y outcome. We recruited 22 general practices (August 2013–September 2014) and 13 corresponding secondary care memory services in London, Hertfordshire, and Essex, United Kingdom. Eligible patients were aged ≥70 y, without a known diagnosis of dementia, living in their own homes. There were 6,387 such patients in 11 intervention practices and 8,171 in the control practices. The primary outcome was cognitive severity on Mini Mental State Examination (MMSE). Main secondary outcomes were proportion of patients consulting their GP with suspected memory disorders and proportion of those referred to memory clinics. There was no between-group difference in cognitive severity at diagnosis (99 intervention, mean MMSE = 22.04, 95% confidence intervals (CIs) = 20.95 to 23.13; 124 control, mean MMSE = 22.59, 95% CI = 21.58 to 23.6; p = 0.48). GP consultations with patients with suspected memory disorders increased in intervention versus control group (odds ratio = 1.41; 95% CI = 1.28, 1.54). There was no between-group difference in the proportions of patients referred to memory clinics (166, 2.5%; 220, 2.7%; p = .077 respectively). The study was limited as we do not know whether the additional patients presenting to GPs had objective as well as subjective memory problems and therefore should have been referred. In addition, we aimed to empower patients but did not do anything to change GP practice. Conclusions: Our intervention to access timely dementia diagnosis resulted in more patients presenting to GPs with memory problems, but no diagnoses increase. We are uncertain as to the reason for this and do not know whether empowering the public and targeting GPs would have resulted in a successful intervention. Future interventions should be targeted at both patients and GPs.

Background: Privacy, ethics, and data access issues pose significant challenges to the timely delivery of health research. Whilst the fundamental drivers to ensure that data access is ethical and satisfies privacy requirements are similar, they are often dealt with in varying ways by different approval processes. Objective: To achieve a consensus across an international panel of health care and informatics professionals on an integrated set of privacy and ethics principles that could accelerate health data access in data-driven health research projects. Method: A three-round consensus development process was used. In round one, we developed a baseline framework for privacy, ethics, and data access based on a review of existing literature in the health, informatics, and policy domains. This was further developed using a two-round Delphi consensus building process involving 20 experts who were members of the International Medical Informatics Association (IMIA) and European Federation of Medical Informatics (EFMI) Primary Health Care Informatics Working Groups. To achieve consensus we required an extended Delphi process. Results: The first round involved feedback on and development of the baseline framework. This consisted of four components: (1) ethical principles, (2) ethical guidance questions, (3) privacy and data access principles, and (4) privacy and data access guidance questions. Round two developed consensus in key areas of the revised framework, allowing the building of a newly, more detailed and descriptive framework. In the final round panel experts expressed their opinions, either as agreements or disagreements, on the ethics and privacy statements of the framework finding some of the previous round disagreements to be surprising in view of established ethical principles. Conclusion: This study develops a framework for an integrated approach to ethics and privacy. Privacy breech risk should not be considered in isolation but instead balanced by potential ethical benefit.

Chronic kidney disease (CKD) is a known risk factor for cardiovascular events and all-cause mortality. We investigate the relationship between CKD stage, proteinuria, hypertension and these adverse outcomes in the people with diabetes. We also study the outcomes of people who did not have monitoring of renal function.

Physician associates [PAs] (also known as physician assistants) are new to the NHS and there is little evidence concerning their contribution in general practice. This study aimed to compare outcomes and costs of same-day requested consultations by PAs with those of GPs.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) causes progressive renal damage and is a leading cause of end-stage renal failure. With emerging therapies it is important to devise a method for early detection. We aimed to identify factors from routine clinical data which can be used to distinguish people with a high likelihood of having ADPKD in a primary health care setting. METHOD: A cross-sectional study was undertaken using data from the Quality Intervention in Chronic Kidney Disease trial extracted from 127 primary care practices in England. The health records of 255 people with ADPKD were compared to the general population. Logistic regression was used to identify clinical features which distinguish ADPKD. These clinical features were used to stratify individual risk using a risk score tool. RESULTS: Renal impairment, proteinuria, haematuria, a diastolic blood pressure over 90 mmHg and multiple antihypertensive medications were more common in ADPKD than the general population and were used to build a regression model (area under the receiver operating characteristic curve; 0.79). Age, gender, haemoglobin and urinary tract infections were not associated with ADPKD. A risk score (range -3 to +10) of ≥0 gave a sensitivity of 70.2% and specificity 74.9% of for detection. CONCLUSIONS: Stratification of ADPKD likelihood from routine data may be possible. This approach could be a valuable component of future screening programs although further longitudinal analyses are needed.

Introduction: The first cardiovascular safety trial in the sodium-glucose co-transporter-2 (SGLT2) inhibitor drug class, the Empagliflozin Cardiovascular Outcomes and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME) trial, demonstrated significant cardiovascular risk reduction with empagliflozin. It is currently not clear what proportions of people with type 2 diabetes (T2DM) have the same high cardiovascular risk as those included in the trial, and will therefore be likely to experience the same cardiovascular benefit. We aimed to identify and describe the proportion of people with T2DM from a representative English national population who have the comparable high cardiovascular risk to those included in the EMPA-REG trial. Method: A cross-sectional analysis of cardiovascular risk in people with T2DM and a subgroup prescribed SGLT2 inhibitors. Patients were identified from the Royal College of General Practitioners Research and Surveillance Centre database. Cardiovascular risk factors were identified from electronic patient records. Results: From 1,238,909 patients at 128 GP practices, we identified 60,327 adults with T2DM (mean age 66.1 years, SD 13.9) of whom 55.6% were male. From these 1642 (2.7%) people had been initiated on an SGLT2 inhibitor (mean age 58.1 years, SD 10.4; 58.8% male). In the complete T2DM group only 15.7% (95% CI 15.5–16.0%) had the same high cardiovascular risk as those included in the EMPA-REG trial. In those already initiated on SGLT2 inhibitors this proportion was 11.1% (95% CI 9.8–12.4%). Whilst the proportion was higher in the oldest age groups, in those 70? years old less than a quarter met the EMPA-REG trial high cardiovascular risk criteria. Conclusions: The EMPA-REG trial results are applicable only to a small proportion of people with T2DM and a smaller proportion of those currently treated with SGLT2 inhibitors. Additional data are required to identify any cardiovascular benefit in people with lower cardiovascular risk.

Concerns have been raised that angiotensin-converting enzyme-inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) might facilitate transmission of severe acute respiratory syndrome coronavirus 2 leading to more severe coronavirus disease (COVID-19) disease and an increased risk of mortality. We aimed to investigate the association between ACE-I/ARB treatment and risk of death amongst people with COVID-19 in the first 6 months of the pandemic. We identified a cohort of adults diagnosed with either confirmed or probable COVID-19 (from 1 January to 21 June 2020) using computerized medical records from the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care database. This comprised 465 general practices in England, United Kingdom with a nationally representative population of 3.7 million people. We constructed mixed-effects logistic regression models to quantify the association between ACE-I/ARBs and all-cause mortality among people with COVID-19, adjusted for sociodemographic factors, comorbidities, concurrent medication, smoking status, practice clustering, and household number. There were 9,586 COVID-19 cases in the sample and 1,463 (15.3%) died during the study period between 1 January 2020 and 21 June 2020. In adjusted analysis ACE-I and ARBs were not associated with all-cause mortality (adjusted odds ratio [OR] 1.02, 95% confidence interval [CI] 0.85-1.21 and OR 0.84, 95% CI 0.67-1.07, respectively). Use of ACE-I/ARB, which are commonly used drugs, did not alter the odds of all-cause mortality amongst people diagnosed with COVID-19. Our findings should inform patient and prescriber decisions concerning continued use of these medications during the pandemic.

Background: Point-of-care testing (POCT) for influenza promises to provide real-time information to influence clinical decision making and improve patient outcomes. Public Health England has published a toolkit to assist implementation of these tests in the UK National Health Service. Objective: A feasibility study will be undertaken to assess the implementation of influenza POCT in primary care as part of a sentinel surveillance network. Methods: We will conduct a mixed methods study to compare the sampling rates in practices using POCT and current virology swabbing practices not using POCT, and to understand the issues and barriers to implementation of influenza POCT in primary care workflows. The study will take place between March and May 2019. It will be nested in general practices that are part of the English national sentinel surveillance network run by the Royal College of General Practitioners Research and Surveillance Centre. The primary outcome is the number of valid influenza swabs taken and tested by the practices involved in the study using the new POCT. Results: A total of 6 practices were recruited, and data collection commenced on March 11, 2019. Moreover, 312 swab samples had been collected at the time of submission of the protocol, which was 32.5% (312/960) of the expected sample size. In addition, 68 samples were positive for influenza, which was 20.1% (68/338) of the expected sample size. Conclusions: To the best of our knowledge, this is the first time an evaluation study has been undertaken on POCT for influenza in general practice in the United Kingdom. This proposed study promises to shed light on the feasibility of implementation of POCT in primary care and on the views of practitioners about the use of influenza POCT in primary care, including its impact on primary care workflows.

Background: Longer medication persistence in type 2 diabetes (T2D) is associated with improved glycaemic control. It is not clear which oral therapies have the best persistence. Objective: To compare medication persistence across different oral therapies in people with T2D. Methods: We performed a retrospective cohort analysis using a primary care based population, the Royal College of General Practitioners Research and Surveillance Centre cohort. We identified new prescriptions for oral diabetes medication in people with type 2 diabetes between 1st January 2004 and 31st July 2015. We compared median persistence across each class (non-persistence defined as prescription gap of ≥ 90 days). We also compared non-persistence between classes, adjusting for confounders, using Cox regression. Confounders included: age, gender, ethnicity, socioeconomic status, alcohol use, smoking status, glycaemic control, diabetes duration, diabetes complications, comorbidities, and number of previous and concurrent diabetes medications. Results: We identified 60,327 adults with T2D. The majority 42,810 (70.9%) of people had one or more oral medications prescribed. In these patients we measured persistence with 55,728 oral medications. Metformin had the longest median persistence (3.04 years; 95% CI 2.94 to 3.12). The adjusted hazard ratios for non-persistence compared with metformin were: sulfonylureas HR 1.20 (1.16 to 1.24), DPP-4 inhibitors HR 1.43 (1.38 to 1.49), thiazolidinediones HR 1.71 (95% CI 1.64-1.77), SGLT2 inhibitors HR 1.04 (0.93 to 1.17), meglitinides HR 2.25 (1.97 to 2.58), and alpha-glucosidase inhibitors HR 2.45 (1.98 to 3.02). The analysis of SGLT2 inhibitors was limited by the short duration of follow-up for this new class. Other factors associated with reduced medication persistence are female gender, younger age, and non-white ethnicity. Conclusions: Persistence is strongly influenced by medication class and should be considered when initiating treatments.

The SARS-CoV-2 pandemic has passed its first peak in Europe. To describe the mortality in England and its association with SARS-CoV-2 status and other demographic and risk factors. Cross-sectional analyses of people with known SARS-CoV-2 status in the Oxford RCGP Research and Surveillance Centre (RSC) sentinel network. Pseudonymised, coded clinical data were uploaded from volunteer general practice members of this nationally representative network ( = 4 413 734). All-cause mortality was compared with national rates for 2019, using a relative survival model, reporting relative hazard ratios (RHR), and 95% confidence intervals (CI). A multivariable adjusted odds ratios (OR) analysis was conducted for those with known SARS-CoV-2 status ( = 56 628, 1.3%) including multiple imputation and inverse probability analysis, and a complete cases sensitivity analysis. Mortality peaked in week 16. People living in households of ≥9 had a fivefold increase in relative mortality (RHR = 5.1, 95% CI = 4.87 to 5.31,

Serum phosphate is a known risk factor for cardiovascular events and mortality in people with chronic kidney disease (CKD), however data on the association of these outcomes with serum phosphate in the general population are scarce. We investigate this relationship in people with and without CKD in a large community-based population.

Background Weight loss, hyperglycaemia and diabetes are known features of pancreatic cancer. We quantified the timing and the amount of changes in body mass index (BMI) and glycated haemoglobin (HbA1c), and their association with pancreatic cancer from five years before diagnosis. Methods A matched case-control study was undertaken within 590 primary care practices in England, United Kingdom. 8,777 patients diagnosed with pancreatic cancer (cases) between 1st January 2007 and 31st August 2020 were matched to 34,979 controls by age, gender and diabetes. Longitudinal trends in BMI and HbA1c were visualised. Odds ratios adjusted for demographic and lifestyle factors (aOR) and 95% confidence intervals (CI) were calculated with conditional logistic regression. Subgroup analyses were undertaken according to the diabetes status. Results Changes in BMI and HbA1c observed for cases on longitudinal plots started one and two years (respectively) before diagnosis. In the year before diagnosis, a 1 kg/m2 decrease in BMI between cases and controls was associated with aOR for pancreatic cancer of 1.05 (95% CI 1.05 to 1.06), and a 1 mmol/mol increase in HbA1c was associated with aOR of 1.06 (1.06 to 1.07). ORs remained statistically significant (p < 0.001) for 2 years before pancreatic cancer diagnosis for BMI and 3 years for HbA1c. Subgroup analysis revealed that the decrease in BMI was associated with a higher pancreatic cancer risk for people with diabetes than for people without (aORs 1.08, 1.06 to 1.09 versus 1.04, 1.03 to 1.05), but the increase in HbA1c was associated with a higher risk for people without diabetes than for people with diabetes (aORs 1.09, 1.07 to 1.11 versus 1.04, 1.03 to 1.04). Conclusions The statistically significant changes in weight and glycaemic control started three years before pancreatic cancer diagnosis but varied according to the diabetes status. The information from this study could be used to detect pancreatic cancer earlier than is currently achieved. However, regular BMI and HbA1c measurements are required to facilitate future research and implementation in clinical practice.

Background: Sodium-glucose co-transporter-2 (SGLT2) inhibitors (gliflozins) are the newest class of medication available to treat type 2 diabetes (T2DM). Recent findings from the first complete cardiovascular safety trial in SGLT2 inhibitors, the Empagliflozin, Cardiovascular Outcomes, and Mortality in type 2 diabetes (EMPA-REG OUTCOMES) trial, demonstrated reduced cardiovascular outcomes in people with high cardiovascular risk. How to apply these findings to clinical practice remains unclear, with questions remaining on who will reap this cardiovascular benefit. Aim: To describe the proportion of people in the real world currently treated with SGLT2 inhibitors who meet the inclusion criteria of the EMPA-REG trial and therefore could expect the cardiovascular benefit identified by the trial. Similarly, to describe the proportion of people from the whole T2DM population who could also expect this same benefit. Design and Setting: Routinely collected data from UK primary care in the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database will be used. The study population will include all people with T2DM within this database (approximately 60,000). We will perform a cross-sectional investigation to describe the characteristics of people currently using SGTL2 inhibitors compared with the population of the EMPA-REG trail. We will similarly compare the characteristics of the RCGP RSC T2DM cohort with the inclusion criteria of the EMPA-REG trial.Method: People with T2DM using a pre-existing verified clinical ontological process will be identified, as will people with prescriptions for SGLT2 inhibitors and other medications using Read coded and other proprietary coding systems. Descriptive statistics will be used to characterise the key clinical characteristics of people with T2DM using SGLT2 inhibitors and to compare these characteristics to people included in EMPA-REG trial; the proportion of people who match the trial criteria will be reported. Planned Outputs: Peer review publication reporting the real world lessons for clinical practice.

Aim To pilot enhanced safety surveillance of seasonal influenza vaccine meeting the European Medicines Agency (EMA) requirement to rapidly detect a significant increase in the frequency or severity of adverse events of interest (AEIs), which may indicate risk from the new season’s vaccine. Study design A prospective passive enhanced safety surveillance combining data collection from adverse drug reaction (ADR) cards with automated collection of pseudonymised routinely collected electronic health record (EHR) data. This study builds on a feasibility study carried out at the start of the 2015/2016 influenza season. We will report influenza vaccine exposure and any AEIs reported via ADR card or recorded directly into the EHR, from the commencement of influenza vaccination and ends as specified by EMA (30 November 2016). Setting Ten volunteer English general practices, primarily using the GSK influenza vaccines. They had selected this vaccine in advance of the study. Participants People who receive a seasonal influenza vaccine, in each age group defined in EMA interim guidance: 6 months to 5 years, 6–12 years, 13–17 years, 18–65 years and >65 years. Outcome measures The primary outcome measure is the rate of AEIs occurring within 7 days postvaccination, using passive surveillance of general practitioner (GP) EHR systems enhanced by a card-based ADR reporting system. Extracted data will be presented overall by brand (Fluarix Tetra vs others), by age strata and risk groups. The secondary outcome measure is the vaccine uptake among the subjects registered in the enrolled general practices.

Aim: To examine whether diabetes and the degree of glycaemic control is associated with an increased risk of acute eye infection, and prescribing of ocular antimicrobial agents. Design and setting: A retrospective cohort study was carried out using the Royal College of General Practitioners Research and Surveillance Centre database (RCGP RSC), a large primary care database in the United Kingdom. We compared ocular infection rates in people aged ≥15 years without diabetes to those with diabetes, both type 1 and type 2. We developed logistic regression models to assess the excess risk in diabetes of: conjunctivitis, blepharitis, stye/chalzion, periorbital cellulitis, keratitis/keratoconjunctivitis, lacrimal gland infection, endopthalmitis, and ocular antimicrobial prescriptions over a six-year period (2010–2015). We also analysed the impact of glycaemic control on infection rates in those with diabetes. All models were adjusted for potential confounders. Results: We analysed infection risk in 889,856 people without diabetes and 48,584 people with diabetes (3273 type 1, and 45,311 type 2). After adjustment for confounders both type 1 and type 2 were associated with increased incidence of conjunctivitis (OR 1.61; 95% CI 1.38–1.88; p < 0.0001 and OR 1.11; 95% CI 1.06–1.16; p < 0.0001 respectively). No association was found with blepharitis, stye/chalzion, periorbital cellulitis, keratitis/keratoconjunctivitis, lacrimal gland infection, and endopthalmitis in the whole population. In subgroup analyses blepharitis was more common in those with type 1 diabetes under 50 years old and endopthalmitis in those under 50 with type 2 diabetes. Glycaemic control was not found to be associated with any infection. Diabetes was also associated with an increased incidence of antimicrobial prescriptions (Type 1 OR 1.69; 95% CI 1.51–1.88; p < 0.0001 and type 2 OR 1.17; 95% CI 1.13–1.20; p < 0.0001). Conclusions: Conjunctivitis is recorded more frequently in people with diabetes. However, no substantial increase in recording of other ocular infections was noted. Infection risk was not found to be associated with the degree of glycaemic control

Background: The Institute of Medicine framework defines six dimensions of quality for healthcare systems: (1) safety, (2) effectiveness, (3) patient centeredness, (4) timeliness of care, (5) efficiency, and (6) equity. Large health datasets provide an opportunity to assess quality in these areas. Objective: To perform an international comparison of the measurability of the delivery of these aims, in people with type 2 diabetes mellitus (T2DM) from large datasets. Method: We conducted a survey to assess healthcare outcomes data quality of existing databases and disseminated this through professional networks. We examined the data sources used to collect the data, frequency of data uploads, and data types used for identifying people with T2DM. We compared data completeness across the six areas of healthcare quality, using selected measures pertinent to T2DM management. Results: We received 14 responses from seven countries (Australia, Canada, Italy, the Netherlands, Norway, Portugal, Turkey and the UK). Most databases reported frequent data uploads and would be capable of near real time analysis of healthcare quality. The majority of recorded data related to safety (particularly medication adverse events) and treatment efficacy (glycaemic control and microvascular disease). Data potentially measuring equity was less well recorded. Recording levels were lowest for patient-centred care, timeliness of care, and system efficiency, with the majority of databases containing no data in these areas. Databases using primary care sources had higher data quality across all areas measured. Conclusion: Data quality could be improved particularly in the areas of patient-centred care, timeliness, and efficiency. Primary care derived datasets may be most suited to healthcare quality assessment.

The use of deep learning is becoming increasingly important in the analysis of medical data such as pattern recognition for classification. The use of primary healthcare computational medical records (CMR) data is vital in prediction of infection prevalence across a population, and decision making at a national scale. To date, the application of machine learning algorithms to CMR data remains under-utilized despite the potential impact for use in diagnostics or prevention of epidemics such as outbreaks of influenza. A particular challenge in epidemiology is how to differentiate incident cases from those that are follow-ups for the same condition. Furthermore, the CMR data are typically heterogeneous, noisy, high dimensional and incomplete, making automated analysis difficult. We introduce a methodology for converting heterogeneous data such that it is compatible with a deep autoencoder for reduction of CMR data. This approach provides a tool for real time visualization of these high dimensional data, revealing previously unknown dependencies and clusters. Our unsupervised nonlinear reduction method can be used to identify the features driving the formation of these clusters that can aid decision making in healthcare applications. The results in this work demonstrate that our methods can cluster more than 97.84% of the data (clusters >5 points) each of which is uniquely described by three attributes in the data: Clinical System (CMR system), Read Code (as recorded) and Read Term (standardized coding). Further, we propose the use of Shannon Entropy as a means to analyse the dispersion of clusters and the contribution from the underlying attributes to gain further insight from the data. Our results demonstrate that Shannon Entropy is a useful metric for analysing both the low dimensional clusters of CMR data, and also the features in the original heterogeneous data. Finally, we find that the entropy of the low dimensional clusters are directly representative of the entropy of the input data (Pearson Correlation = 0.99, R2 = 0.98) and therefore the reduced data from the deep autoencoder is reflective of the original CMR data variability.

Background: Medical informatics, or biomedical and health informatics (BMHI), has become an established scientific discipline. In all such disciplines there is a certain inertia to persist in focusing on well-established research areas and to hold on to well-known research methodologies rather than adopting new ones, which may be more appropriate. Objectives: To search for answers to the following questions: What are research fields in informatics, which are not being currently adequately addressed, and which methodological approaches might be insufficiently used? Do we know about reasons? What could be consequences of change for research and for education? Methods: Outstanding informatics scientists were invited to three panel sessions on this topic in leading international conferences (MIE 2015, Medinfo 2015, HEC 2016) in order to get their answers to these questions. Results: A variety of themes emerged in the set of answers provided by the panellists. Some panellists took the theoretical foundations of the field for granted, while several questioned whether the field was actually grounded in a strong theoretical foundation. Panellists proposed a range of suggestions for new or improved approaches, methodologies, and techniques to enhance the BMHI research agenda. Conclusions: The field of BMHI is on the one hand maturing as an academic community and intellectual endeavour. On the other hand vendor-supplied solutions may be too readily and uncritically accepted in health care practice. There is a high chance that BMHI will continue to flourish as an important discipline; its innovative interventions might then reach the original objectives of advancing science and improving health care outcomes.

Objectives We analyzed hepatitis B surface antigen (HBsAg) screening and seropositivity within a network of 419 general practices representative of all regions of England. Methods Information was extracted using pseudonymized registration data. Predictors of HBsAg seropositivity were explored in models that considered age, gender, ethnicity, time at the current practice, practice location and associated deprivation index, and presence of nationally endorsed screen indicators including pregnancy, men who have sex with men (MSM), history of injecting drug use (IDU), close HBV contact or imprisonment, and diagnosis of blood-borne or sexually transmitted infections. Results Among 6,975,119 individuals, 192,639 (2.8 %) had a screening record, including 3.6–38.6 % of those with a screen indicator, and 8065 (0.12 %) had a seropositive record. The odds of seropositivity were highest in London, in the most deprived neighborhoods, among minority ethnic groups, and in people with screen indicators. Seroprevalence exceeded 1 % in people from high-prevalence countries, MSM, close HBV contacts, and people with a history of IDU or a recorded diagnosis of HIV, HCV, or syphilis. Overall, 1989/8065 (24.7 %) had a recorded referral to specialist hepatitis care. Conclusions In England, HBV infection is associated with poverty. There are unrealized opportunities to promote access to diagnosis and care for those affected.

Background: The COVID-19 pandemic has resulted in unprecedented impact on the day to day lives of people, with several features potentially adversely affecting mental health. There is growing evidence of the size of the impact of COVID-19 on mental health, but much of this is from ongoing population surveys using validated mental health scores. Objective: This study investigated the impact of the pandemic and control measures on mental health conditions presenting to a spectrum of national healthcare services monitored using real-time syndromic surveillance in England. Methods: We conducted a retrospective observational descriptive study of mental health presentations (those calling the national medical helpline, NHS 111, consulting general practitioners in and out-of-hours, calling ambulance services and attending emergency departments) between 1 January 2019 to 30 September 2020. Estimates for the impact of lockdown measures were provided using an interrupted time series analysis. Results: Mental health presentations showed a marked decrease during the early stages of the pandemic. Post-lockdown, attendances for mental health conditions reached higher than pre-pandemic levels across most systems; a rise of 10% compared to expected for NHS 111 and 21% for GP out-of-hours whilst the number of consultations to in-hours GPs was 13% lower compared to the same time last year. Increases were observed in calls to NHS 111 for sleep problems. Conclusions: These analyses showed marked changes in the healthcare attendances and prescribing for common mental health issues, across a spectrum of healthcare provision, with some of these changes persisting. The reasons for such changes are likely to be complex and multifactorial. The impact of the pandemic on mental health may not be fully understood for some time, and therefore these syndromic indicators should continue to be monitored.

In the UK secondary care setting, the case for physician associates is based on the cover and stability they might offer to medical teams. We assessed the extent of their adoption and deployment - that is, their current usage and the factors supporting or inhibiting their inclusion in medical teams - using an electronic, self-report survey of medical directors of acute and mental health NHS trusts in England. Physician associates - employed in small numbers, in a range of specialties, in 20 of the responding trusts - were reported to have been employed to fill gaps in medical staffing and support medical specialty trainees. Inhibiting factors were commonly a shortage of physician associates to recruit and lack of authority to prescribe, as well as a lack of evidence and colleague resistance. Our data suggest there is an appetite for employment of physician associates while practical and attitudinal barriers are yet to be fully overcome.

Like other health care systems, the National Health Service (NHS) in England has looked to new staffing configurations faced with medical staff shortages and rising costs. One solution has been to employ physician associates (PAs). PAs are trained in the medical model to assess, diagnose and commence treatment under the supervision of a physician. This paper explores the perceived effects on professional boundaries and relationships of introducing this completely new professional group. It draws on data from a study, completed in 2014, which examined the contribution of PAs working in general practice. Data were gathered at macro, meso and micro levels of the health care system. At the macro and meso level data were from policy documents, interviews with civil servants, senior members of national medical and nursing organisations, as well as regional level NHS managers (n = 25). At the micro level data came from interviews with General Practitioners, nurse practitioners and practice staff (n = 30) as well as observation of clinical and professional meetings. Analysis was both inductive and also framed by the existing theories of a dynamic system of professions. It is argued that professional boundaries become malleable and subject to negotiation at the micro level of service delivery. Stratification within professional groups created differing responses between those working at macro, meso and micro levels of the system; from acceptance to hostility in the face of a new and potentially competing, occupational group. Overarching this state agency was the requirement to underpin legislatively the shifts in jurisdictional boundaries, such as prescribing required for vertical substitution for some of the work of doctors.

Aim: To determine whether achieving early glycaemic control, and any subsequent glycaemic variability, was associated with any change in the risk of major adverse cardiovascular events (MACE). Materials and Methods A retrospective cohort analysis from the Oxford-Royal College of General Practitioners Research and Surveillance Centre database—a large, English primary care network—was conducted. We followed newly diagnosed patients with type 2 diabetes, on or after 1 January 2005, aged 25 years or older at diagnosis, with HbA1c measurements at both diagnosis and after 1 year, plus five or more measurements of HbA1c thereafter. Three glycaemic bands were created: groups A (HbA1c A transition had a reduced risk of MACE (HR 0.75; 95% CI 0.60-0.94; P = .014), whereas group C->C had HR 1.21 (0.81-1.81; P = .34). Compared with the lowest glycaemic variability score, the greatest variability increased the risk of MACE (HR 1.51; 1.11-2.06; P = .0096). Conclusion Early control of HbA1c improved cardiovascular outcomes in type 2 diabetes, although subsequent glycaemic variability had a negative effect on an individual's risk.

Background: Governments and health care providers are keen to find innovative ways to deliver care more efficiently. Interest in electronic consultation (e-consultation) has grown, but the evidence of benefit is uncertain. Objective: This study aimed to assess the evidence of delivering e-consultation using secure email and messaging or video links in primary care. Methods: A systematic review was conducted on the use and application of e-consultations in primary care. We searched 7 international databases (MEDLINE, EMBASE, CINAHL, Cochrane Library, PsycINFO, EconLit, and Web of Science; 1999-2017), identifying 52 relevant studies. Papers were screened against a detailed inclusion and exclusion criteria. Independent dual data extraction was conducted and assessed for quality. The resulting evidence was synthesized using thematic analysis. Results: This review included 57 studies from a range of countries, mainly the United States (n=30) and the United Kingdom (n=13). There were disparities in uptake and utilization toward more use by younger, employed adults. Patient responses to e-consultation were mixed. Patients reported satisfaction with services and improved self-care, communication, and engagement with clinicians. Evidence for the acceptability and ease of use was strong, especially for those with long-term conditions and patients located in remote regions. However, patients were concerned about the privacy and security of their data. For primary health care staff, e-consultation delivers challenges around time management, having the correct technological infrastructure, whether it offers a comparable standard of clinical quality, and whether it improves health outcomes. Conclusions: E-consultations may improve aspects of care delivery, but the small scale of many of the studies and low adoption rates leave unanswered questions about usage, quality, cost, and sustainability. We need to improve e-consultation implementation, demonstrate how e-consultations will not increase disparities in access, provide better reassurance to patients about privacy, and incorporate e-consultation as part of a manageable clinical workflow.

The recent publication by Jessica Metcalf and others (Aug 13, p 728),1 calls for the establishment of a World Serum Bank; something we feel should be titled a World Serology Bank given its emphasis on monitoring changes in the immune response to infections. A possible rapid and cost-effective way of setting this up would be to use existing primary care sentinel networks such as the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC).2

Background:Increasing demand for hospital services and staff shortages has led NHS organisations to review workforce configurations. One solution has been to employ physician associates (PAs). PAs are trained over 2 years at postgraduate level to work to a supervising doctor. Little is currently known about the roles and impact of PAs working in hospitals in England. Objectives:(1) To investigate the factors influencing the adoption and deployment of PAs within medical and surgical teams in secondary care and (2) to explore the contribution of PAs, including their impact on patient experiences, organisation of services, working practices, professional relationships and service costs, in acute hospital care. Methods:This was a mixed-methods, multiphase study. It comprised a systematic review, a policy review, national surveys of medical directors and PAs, case studies within six hospitals utilising PAs in England and a pragmatic retrospective record review of patients in emergency departments (EDs) attended by PAs and Foundation Year 2 (FY2) doctors. Results:The surveys found that a small but growing number of hospitals employed PAs. From the case study element, it was found that medical and surgical teams mainly used PAs to provide continuity to the inpatient wards. Their continuous presence contributed to smoothing patient flow, accessibility for patients and nurses in communicating with doctors and releasing doctors’ (of all grades) time for more complex patients and for attending to patients in clinic and theatre settings. PAs undertook significant amounts of ward-based clinical administration related to patients’ care. The lack of authority to prescribe or order ionising radiation restricted the extent to which PAs assisted with the doctors’ workloads, although the extent of limitation varied between teams. A few consultants in high-dependency specialties considered that junior doctors fitted their team better. PAs were reported to be safe, as was also identified from the review of ED patient records. A comparison of a random sample of patient records in the ED found no difference in the rate of unplanned return for the same problem between those seen by PAs and those seen by FY2 doctors (odds ratio 1.33, 95% confidence interval 0.69 to 2.57; p = 0.40). In the ED, PAs were also valued for the continuity they brought and, as elsewhere, their input in inducting doctors in training into local clinical and hospital processes. Patients were positive about the care PAs provided, although they were not able to identify what or who a PA was; they simply saw them as part of the medical or surgical team looking after them. Although the inclusion of PAs was thought to reduce the need for more expensive locum junior doctors, the use of PAs was primarily discussed in terms of their contribution to patient safety and patient experience in contrast to utilising temporary staff. Limitations:PAs work within medical and surgical teams, such that their specific impact cannot be distinguished from that of the whole team. Conclusions:PAs can provide a flexible advanced clinical practitioner addition to the secondary care workforce without drawing from existing professions. However, their utility in the hospital setting is unlikely to be fully realised without the appropriate level of regulation and attendant authority to prescribe medicines and order ionising radiation within their scope of practice. Future research:Comparative investigation is required of patient experience, outcomes and service costs in single, secondary care specialties with and without PAs and in comparison with other types of advanced clinical practitioners. Study registration:The systematic review component of this study is registered as PROSPERO CRD42016032895. Funding:The National Institute for Health Research Health Services and Delivery Research programme.

This report contains new and follow-up metric data relating to the eight main recommendations of the Lancet Standing Commission on Liver Disease in the UK, which aim to reduce the unacceptable harmful consequences of excess alcohol consumption, obesity, and viral hepatitis. For alcohol, we provide data on alcohol dependence, damage to families, and the documented increase in alcohol consumption since removal of the above-inflation alcohol duty escalator. Alcoholic liver disease will shortly overtake ischaemic heart disease with regard to years of working life lost. The rising prevalence of overweight and obesity, affecting more than 60% of adults in the UK, is leading to an increasing liver disease burden. Favourable responses by industry to the UK Government’s soft drinks industry levy have been seen, but the government cannot continue to ignore the number of adults being affected by diabetes, hypertension, and liver disease. New direct-acting antiviral drugs for the treatment of chronic hepatitis C virus infection have reduced mortality and the number of patients requiring liver transplantation, but more screening campaigns are needed for identification of infected people in high-risk migrant communities, prisons, and addiction centres. Provision of care continues to be worst in regions with the greatest socioeconomic deprivation, and deficiencies exist in training programmes in hepatology for specialist registrars. Firm guidance is needed for primary care on the use of liver blood tests in detection of early disease and the need for specialist referral. This report also brings together all the evidence on costs to the National Health Service and wider society, in addition to the loss of tax revenue, with alcohol misuse in England and Wales costing £21 billion a year (possibly up to £52 billion) and obesity costing £27 billion a year (treasury estimates are as high as £46 billion). Voluntary restraints by the food and drinks industry have had little effect on disease burden, and concerted regulatory and fiscal action by the UK Government is essential if the scale of the medical problem, with an estimated 63 000 preventable deaths over the next 5 years, is to be addressed.

Abstract. Immunisation is an important part of health care and adverse events following immunisation (AEFI) are relatively rare. AEFI can be detected through long term follow up of a cohort or from looking for signals from real world, routine data; from different health systems using a variety of clinical coding systems. Mapping these is a challenging aspect of integrating data across borders. Ontological representations of clinical concepts provide a method to map similar concepts, in this case AEFI across different coding systems. We describe a method using ontologies to be flag definite, probable or possible cases. We use Guillain- Barre syndrome (GBS) as an AEFI to illustrate this method, and the Brighton collaboration’s case definition of GBS as the gold standard. Our method can be used to flag definite, probable or possible cases of GBS. Whilst there has been much research into the use of ontologies in immunisation these have focussed on database interrogation; where ours looks to identify varying signal strength.

Background Chronic viral hepatitis (CVH) is a leading contributor to the UK liver disease epidemic, with global migration from high prevalence areas (e.g., South Asia). Despite international guidance for testing high-risk groups in line with elimination targets, there is no consensus on how to achieve this. The objectives of this study were to assess the following: (1) the feasibility of recruiting South Asian migrants to view an educational film on CVH, (2) the effectiveness of the film in promoting testing and increasing knowledge of CVH, and (3) the methodological issues relevant to scale-up to a randomized controlled trial. Methods South Asian migrants were recruited to view the film (intervention) in community venues (primary care, religious, community), with dried blood spot CVH testing offered immediately afterwards. Pre/post-film questionnaires assessed the effectiveness of the intervention. Results Two hundred and nineteen first-generation migrants ≥18 years of age (53% female) were recruited to view the film at the following sites: religious, n = 112 (51%), community n = 98 (45%), and primary care, n = 9 (4%). One hundred and eighty-four (84%) underwent CVH testing; hepatitis B core antibody or hepatitis C antibody positivity demonstrated exposure in 8.5%. Pre-intervention (n = 173, 79%) and post-intervention (n = 154, 70%) questionnaires were completed. Conclusions This study demonstrated the feasibility of recruiting first-generation migrants to view a community-based educational film promoting CVH testing in this higher risk group, confirming the value of developing interventions to facilitate the global World Health Organization plan for targeted case finding and elimination, and a future randomized controlled trial. We highlight the importance of culturally relevant interventions including faith and culturally sensitive settings, which appear to minimize logistical issues and effectively engage minority groups, allowing ease of access to individuals ‘at risk’.

Background There are limited case-mix classification systems for primary care settings which are applicable when considering the optimal clinical skill mix to provide services. Aim To develop a case-mix classification system (CMCS) and test its impact on analyses of patient outcomes by clinician type, using example data from physician associates’ (PAs) and GPs' consultations with same-day appointment patients. Design & setting Secondary analysis of controlled observational data from six general practices employing PAs and six matched practices not employing PAs in England. Method Routinely-collected patient consultation records (PA n = 932, GP n = 1154) were used to design the CMCS (combining problem codes, disease register data, and free text); to describe the case-mix; and to assess impact of statistical adjustment for the CMCS on comparison of outcomes of consultations with PAs and with GPs. Results A CMCS was developed by extending a system that only classified 18.6% (213/1147) of the presenting problems in this study's data. The CMCS differentiated the presenting patient’s level of need or complexity as: acute, chronic, minor problem or symptom, prevention, or process of care, applied hierarchically. Combination of patient and consultation-level measures resulted in a higher classification of acuity and complexity for 639 (30.6%) of patient cases in this sample than if using consultation level alone. The CMCS was a key adjustment in modelling the study’s main outcome measure, that is rate of repeat consultation. Conclusion This CMCS assisted in classifying the differences in case-mix between professions, thereby allowing fairer assessment of the potential for role substitution and task shifting in primary care, but it requires further validation.

Ensuring that healthcare teams have a mix of skilled professionals to meet patient needs and deliver safe and cost-effective services is a major imperative in all health services. The health services in the UK, like a number of other countries, have been exploring the contribution that physician assistants (PAs) can make to healthcare teams including primary care. PAs are well established in the USA, where they have a recognized qualification and undertake physical examinations, investigations, diagnosis, treatment and prescribing within their scope of practice as agreed with their supervising doctor. The first UK-trained PAs graduated in 2009 from post-graduate courses, which are modeled closely on those in the USA to a UK agreed set of competencies and curriculum. There is evidence of the substantive employment of PAs in primary care teams in England. The UK has a well-developed primary care system, with most care delivered via general practice teams which generally include a mix of medical, nursing and support staff. The extent of the employment of PAs in primary care in the England and their contribution within the team to patient care is unknown. This paper reports on a survey that investigated these questions.

A rating scale was developed to assess the contribution made by computer software towards the delivery of a quality consultation, with the purpose of informing the development of the next generation of systems. Two software programmes were compared, using this scale to test their ability to enable or inhibit the delivery of an ideal consultation with a patient with heart disease. The context was a general practice based, nurse run clinic for the secondary prevention of heart disease. One of the programmes was customized for this purpose; the other was a standard general practice programme. Consultations were video-recorded, and then assessed by an expert panel using the new assessment tool. Both software programmes were oriented towards the implementation of the evidence, rather than facilitating patient-centred practice. The rating scale showed, not surprisingly, significantly greater support from the customized software in the consultation in five out of eight areas. However, the scale's reliability measured by Cronbach's Alpha, was sub-optimal. With further refinement, this rating scale may become a useful tool that will inform software developers of the effectiveness of their programmes in the consultation, and suggest where they need development. © 2002 Informa UK Ltd All rights reserved.

The MediPlus database collects anonymized information from generalpractice computer systems in the United Kingdom, for research purposes. Data quality markers are collated and fed back to the participating general practitioners. The authors examined whether this feedback had a significant effect on data quality.

Introduction Acute gastroenteritis (AGE) is a highly transmissible condition. Determining characteristics of household transmission will facilitate development of prevention strategies and reduce the burden of this disease. We are carrying out this study to describe household transmission of medically attended AGE, and explore whether there is an increased incidence in households with young children. Methods and analysis This study used the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care sentinel network, comprising data from 1 750 167 registered patients (August 2017 database). We conducted a novel analysis using a ’household key', to identify patients within the same household (n=811 027, mean 2.16 people). A 25-year repeated cross-sectional study will explore the incidence of medically attended AGE overall and then a 5-year retrospective cohort study will describe household transmission of AGE. The cross-sectional study will include clinical data for a 25-year period—1 January 1992 until the 31 December 2017. We will describe the incidence of AGE by age-band and gender, and trends in incidence. The 5-year study will use Poisson and quasi-Poisson regression to identify characteristics of individuals and households to predict medically attended AGE transmitted in the household. This will include whether the household contained a child under 5 years and the age category of the first index case (whether adult or child under 5 years). If there is overdispersion and zero-inflation we will compare results with negative binomial to handle these issues. Ethics and dissemination All RCGP RSC data are pseudonymised at the point of data extraction. No personally identifiable data are required for this investigation. The protocol follows STrengthening the Reporting of OBservational studies in Epidemiology guidelines (STROBE). The study results will be published in a peer-review journal, the dataset will be available to other researchers.

Background: Physician associates are new to English general practice and set to expand in numbers. Objective: To investigate the patients’ perspective on consulting with physician associates in general practice. Design: A qualitative study, using semi-structured interviews, with thematic analysis. Setting and participants: Thirty volunteer patients of 430 who had consulted ­physician associates for a same-day appointment and had returned a satisfaction survey, in six general practices employing physician associates in England. Findings: Some participants only consulted once with a physician associate and others more frequently. The conditions consulted for ranged from minor illnesses to those requiring immediate hospital admission. Understanding the role of the physician associate varied from ‘certain and correct’ to ‘uncertain’, to ‘certain and incorrect’, where the patient believed the physician associate to be a doctor. Most, but not all, reported positive experiences and outcomes of their consultation, with some choosing to consult the physician. Those with negative experiences described problems when the limits of the role were reached, requiring additional GP consultations or prescription delay. Trust and confidence in the physician associate was derived from trust in the NHS, the general practice and the individual physician associate. Willingness to consult a physician associate was contingent on the patient’s assessment of the severity or complexity of the problem and the desire for provider continuity. Conclusion: Patients saw physician associates as an appropriate general practitioner substitute. Patients’ experience could inform delivery redesign.

There is no standard method of publishing the code ranges in research using routine data. We report how code selection affects the reported prevalence and precision of results.