Rohini Mathur

Data Resource Profile: Clinical Practice Research Datalink (CPRD)

The Clinical Practice Research Datalink (CPRD) is an ongoing primary care database of anonymised medical records from general practitioners, with coverage of over 11.3 million patients from 674 practices in the UK. With 4.4 million active (alive, currently registered) patients meeting quality criteria, approximately 6.9% of the UK population are included and patients are broadly representative of the UK general population in terms of age, sex and ethnicity. General practitioners are the gatekeepers of primary care and specialist referrals in the UK. The CPRD primary care database is therefore a rich source of health data for research, including data on demographics, symptoms, tests, diagnoses, therapies, health-related behaviours and referrals to secondary care. For over half of patients, linkage with datasets from secondary care, disease-specific cohorts and mortality records enhance the range of data available for research. The CPRD is very widely used internationally for epidemiological research and has been used to produce over 1000 research studies, published in peer-reviewed journals across a broad range of health outcomes. However, researchers must be aware of the complexity of routinely collected electronic health records, including ways to manage variable completeness, misclassification and development of disease definitions for research.

Risk models and scores for type 2 diabetes: systematic review

Objective To evaluate current risk models and scores for type 2 diabetes and inform selection and implementation of these in practice. Design Systematic review using standard (quantitative) and realist (mainly qualitative) methodology. Inclusion criteria Papers in any language describing the development or external validation, or both, of models and scores to predict the risk of an adult developing type 2 diabetes. Data sources Medline, PreMedline, Embase, and Cochrane databases were searched. Included studies were citation tracked in Google Scholar to identify follow-on studies of usability or impact. Data extraction Data were extracted on statistical properties of models, details of internal or external validation, and use of risk scores beyond the studies that developed them. Quantitative data were tabulated to compare model components and statistical properties. Qualitative data were analysed thematically to identify mechanisms by which use of the risk model or score might improve patient outcomes. Results 8864 titles were scanned, 115 full text papers considered, and 43 papers included in the final sample. These described the prospective development or validation, or both, of 145 risk prediction models and scores, 94 of which were studied in detail here. They had been tested on 6.88 million participants followed for up to 28 years. Heterogeneity of primary studies precluded meta-analysis. Some but not all risk models or scores had robust statistical properties (for example, good discrimination and calibration) and had been externally validated on a different population. Genetic markers added nothing to models over clinical and sociodemographic factors. Most authors described their score as “simple” or “easily implemented,” although few were specific about the intended users and under what circumstances. Ten mechanisms were identified by which measuring diabetes risk might improve outcomes. Follow-on studies that applied a risk score as part of an intervention aimed at reducing actual risk in people were sparse. Conclusion Much work has been done to develop diabetes risk models and scores, but most are rarely used because they require tests not routinely available or they were developed without a specific user or clear use in mind. Encouragingly, recent research has begun to tackle usability and the impact of diabetes risk scores. Two promising areas for further research are interventions that prompt lay people to check their own diabetes risk and use of risk scores on population datasets to identify high risk “hotspots” for targeted public health interventions.

Completeness and usability of ethnicity data in UK-based primary care and hospital databases

Background Ethnicity recording across the National Health Service (NHS) has improved dramatically over the past decade. This study profiles the completeness, consistency and representativeness of routinely collected ethnicity data in both primary care and hospital settings. Methods Completeness and consistency of ethnicity recording was examined in the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES), and the ethnic breakdown of the CPRD was compared with that of the 2011 UK censuses. Results 27.1% of all patients in the CPRD (1990–2012) have ethnicity recorded. This proportion rises to 78.3% for patients registered since April 2006. The ethnic breakdown of the CPRD is comparable to the UK censuses. 79.4% of HES inpatients, 46.8% of outpatients and 26.8% of A&E patients had their ethnicity recorded. Amongst those with ethnicity recorded on >1 occasion, consistency was over 90% in all data sets except for HES inpatients. Combining CPRD and HES increased completeness to 97%, with 85% of patients having the same ethnicity recorded in both databases. Conclusions Using CPRD ethnicity from 2006 onwards maximizes completeness and comparability with the UK population. High concordance within and across NHS sources suggests these data are of high value when examining the continuum of care. Poor completeness and consistency of A&E and outpatient data render these sources unreliable.

Patient safety and estimation of renal function in patients prescribed new oral anticoagulants for stroke prevention in atrial fibrillation: a cross-sectional study

Objective In clinical trials of dabigatran and rivaroxaban for stroke prevention in atrial fibrillation (AF), drug eligibility and dosing were determined using the Cockcroft-Gault equation to estimate creatine clearance as a measure of renal function. This cross-sectional study aimed to compare whether using estimated glomerular filtration rate (eGFR) by the widely available and widely used Modified Diet in Renal Disease (MDRD) equation would alter prescribing or dosing of the renally excreted new oral anticoagulants. Participants Of 4712 patients with known AF within a general practitioner-registered population of 930 079 in east London, data were available enabling renal function to be calculated by both Cockcroft-Gault and MDRD methods in 4120 (87.4%). Results Of 4120 patients, 2706 were <80 years and 1414 were ≥80 years of age. Among those ≥80 years, 14.9% were ineligible for dabigatran according to Cockcroft-Gault equation but would have been judged eligible applying MDRD method. For those <80 years, 0.8% would have been incorrectly judged eligible for dabigatran and 5.3% would have received too high a dose. For rivaroxaban, 0.3% would have been incorrectly judged eligible for treatment and 13.5% would have received too high a dose. Conclusions Were the MDRD-derived eGFR to be used instead of Cockcroft-Gault in prescribing these new agents, many elderly patients with AF would either incorrectly become eligible for them or would receive too high a dose. Safety has not been established using the MDRD equation, a concern since the risk of major bleeding would be increased in patients with unsuspected renal impairment. Given the potentially widespread use of these agents, particularly in primary care, regulatory authorities and drug companies should alert UK doctors of the need to use the Cockcroft-Gault formula to calculate eligibility for and dosing of the new oral anticoagulants in elderly patients with AF and not rely on the MDRD-derived eGFR.

Remote ischemic preconditioning has a neutral effect on the incidence of kidney injury after coronary artery bypass graft surgery

Acute kidney injury (AKI) is a frequent complication of cardiac surgery and usually occurs in patients with preexisting chronic kidney disease (CKD). Remote ischemic preconditioning (RIPC) may mitigate the renal ischemia-reperfusion injury associated with cardiac surgery and may be a preventive strategy for postsurgical AKI. We undertook a randomized controlled trial of RIPC to prevent AKI in 86 patients with CKD (estimated glomerular filtration rate under 60 ml/min per 1.73 m(2)) undergoing coronary artery bypass graft (CABG) surgery. Forty-three patients each were randomized to receive standard care with or without RIPC consisting of three 5-minute cycles of forearm ischemia followed by reperfusion. The primary end point was the development of AKI defined as an increase in serum creatinine concentration over 0.3 mg/dl within 48 h of surgery. Secondary end points included a comparison between the study and control groups of several serum biomarkers of renal injury including cystatin-C, neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 (IL-18), and urinary biomarkers including NGAL, IL-18, and kidney injury molecule-1 measured at 6, 12, and 24 h after CABG, and the 72-h serum troponin T concentration area under the curve as a marker of myocardial injury. Clinical and operative characteristics were similar between the preconditioned and control groups. AKI developed in 12 patients in both groups within 48 h of CABG. There were no significant differences between the two groups in the concentrations of any of the serum or urinary biomarkers of renal or cardiac injury after CABG. Thus, RIPC induced by forearm ischemia-reperfusion had no effect on the frequency of AKI after CABG in patients with CKD.

Cardiovascular multimorbidity: the effect of ethnicity on prevalence and risk factor management

BACKGROUND Multimorbidity is common in primary care populations. Within cardiovascular disease, important differences in disease prevalence and risk factor management by ethnicity are recognised. AIM To examine the population burden of cardiovascular multimorbidity and the management of modifiable risk factors by ethnicity. DESIGN AND SETTING Cross-sectional study of general practices (148/151) in the east London primary care trusts of Tower Hamlets, City and Hackney, and Newham, with a total population size of 843 720. METHOD Using MIQUEST, patient data were extracted from five cardiovascular registers. Logistic regression analysis was used to examine the risk of being multimorbid by ethnic group, and the control of risk factors by ethnicity and burden of cardiovascular multimorbidity. RESULTS The crude prevalence of cardiovascular multimorbidity among patients with at least one cardiovascular condition was 34%. People of non-white ethnicity are more likely to be multimorbid than groups of white ethnicity, with adjusted odds ratios of 2.04 (95% confidence interval [CI] = 1.94 to 2.15) for South Asians and 1.23 (95% CI = 1.18 to 1.29) for groups of black ethnicity. Achievement of targets for blood pressure, cholesterol, and glycated haemoglobin (HbA(1c)) was higher for patients who were multimorbid than unimorbid. For cholesterol and blood pressure, South Asian patients achieved better control than those of white and black ethnicity. For HbA(1c) levels, patients of white ethnicity had an advantage over other groups as the morbidity burden increased. CONCLUSION The burden of multiple disease varies by ethnicity. Risk factor management improves with increasing levels of cardiovascular multimorbidity, but clinically important differences by ethnicity remain and contribute to health inequalities.

Ethnic and social disparity in glycaemic control in type 2 diabetes; cohort study in general practice 2004-9.

Objective To determine whether ethnic group differences in glycated haemoglobin (HbA1c) changed over a 5-year period in people on medication for type 2 diabetes. Design Open cohort in 2004–9. Setting Electronic records of 100 of the 101 general practices in two inner London boroughs. Participants People aged 35 to 74 years on medication for type 2 diabetes. Main outcome measures Mean HbA1c and proportion with HbA1c controlled to ≤7.5%. Results In this cohort of 24,111 people, 22% were White, 58% South Asian and 17% Black African/Caribbean. From 2004 to 2009 mean HbA1c improved from 8.2% to 7.8% for White, from 8.5% to 8.0% for Black African/Caribbean and from 8.5% to 8.0% for South Asian people. The proportion with HbA1c controlled to 7.5% or less, increased from 44% to 56% in White, 38% to 53% in Black African/Caribbean and 34% to 48% in South Asian people. Ethnic group and social deprivation were independently associated with HbA1c. South Asian and Black African/Caribbean people were treated more intensively than White people. Conclusion HbA1c control improved for all ethnic groups between 2004–9. However, South Asian and Black African/Caribbean people had persistently worse control despite more intensive treatment and significantly more improvement than White people. Higher social deprivation was independently associated with worse control.

Feasibility study of geospatial mapping of chronic disease risk to inform public health commissioning.

Objective To explore the feasibility of producing small-area geospatial maps of chronic disease risk for use by clinical commissioning groups and public health teams. Study design Cross-sectional geospatial analysis using routinely collected general practitioner electronic record data. Sample and setting Tower Hamlets, an inner-city district of London, UK, characterised by high socioeconomic and ethnic diversity and high prevalence of non-communicable diseases. Methods The authors used type 2 diabetes as an example. The data set was drawn from electronic general practice records on all non-diabetic individuals aged 25–79 years in the district (n=163 275). The authors used a validated instrument, QDScore, to calculate 10-year risk of developing type 2 diabetes. Using specialist mapping software (ArcGIS), the authors produced visualisations of how these data varied by lower and middle super output area across the district. The authors enhanced these maps with information on examples of locality-based social determinants of health (population density, fast food outlets and green spaces). Data were piloted as three types of geospatial map (basic, heat and ring). The authors noted practical, technical and information governance challenges involved in producing the maps. Results Usable data were obtained on 96.2% of all records. One in 11 adults in our cohort was at ‘high risk’ of developing type 2 diabetes with a 20% or more 10-year risk. Small-area geospatial mapping illustrated ‘hot spots’ where up to 17.3% of all adults were at high risk of developing type 2 diabetes. Ring maps allowed visualisation of high risk for type 2 diabetes by locality alongside putative social determinants in the same locality. The task of downloading, cleaning and mapping data from electronic general practice records posed some technical challenges, and judgement was required to group data at an appropriate geographical level. Information governance issues were time consuming and required local and national consultation and agreement. Conclusions Producing small-area geospatial maps of diabetes risk calculated from general practice electronic record data across a district-wide population was feasible but not straightforward. Geovisualisation of epidemiological and environmental data, made possible by interdisciplinary links between public health clinicians and human geographers, allows presentation of findings in a way that is both accessible and engaging, hence potentially of value to commissioners and policymakers. Impact studies are needed of how maps of chronic disease risk might be used in public health and urban planning.

Improving MMR vaccination rates: herd immunity is a realistic goal

Problem As measles is a highly infectious disease, the United Kingdom recommendation is for at least 95% of children to receive a first vaccination with the measles, mumps, and rubella (MMR) vaccine before age 2 years and a booster before age 5 years to achieve herd immunity and prevent outbreaks. Reported vaccination rates for England have improved since a low level in 2003-4. Coverage for London is consistently lower than for England, however, and concerns have been expressed that there could be an epidemic of measles in the capital. Design Observational time series study. Setting London Borough of Tower Hamlets. Key measurements for improvement Uptake rates for childhood vaccinations. The key target was to reach 95% coverage for the first MMR vaccine before age 2 years. Strategies for change Financial support for the development of geographically based networks of general practices. Commissioning of care packages, incentivising delivery of high quality integrated care with network level vaccination targets of 95%. Innovative use of information technology to enable robust call and recall processes, active follow-up of defaulters, and increased knowledge about the demography of the children most difficult to reach. Effects of change The development of networks of practices facilitated collaborative working among primary care clinicians and other stakeholders; peer review of achievements; and an element of healthy competition. Uptake improved for all childhood vaccinations, and to herd immunity levels for most. Uptake of the first MMR vaccine before age 2 years rose from 80% in September 2009 to 94% in March 2011. Lessons learnt Achieving herd immunity for childhood vaccinations is an achievable target in an ethnically mixed, socially deprived inner city borough. The ability to identify characteristics of the difficult to reach groups, including significant differences in uptake across different ethnicities, will allow targeted interventions that may further improve overall coverage.

Ethnicity and stroke risk in patients with atrial fibrillation

Objective To examine the prevalence of atrial fibrillation (AF) and stroke risk by ethnic group in south and east London; to compare classification with CHA2DS2VASc and CHADS2; to examine the appropriateness of anticoagulant treatment and historic trends in prescribing by gender, age, and ethnicity. Design Cross-sectional study. Setting Routine general practice records from south and east London. Patients Patients aged 18 years or over with AF. Main outcome measures Risk of stroke by CHA2DS2VASc and CHADS2 score, and prescription of anticoagulant. Results In 2011, we identified 6292 patients with AF, with an age adjusted prevalence of 0.63% (1.2% white, 0.4% black African/Caribbean and 0.2% South Asian). 93% of the AF population were at high risk of stroke with a CHA2DS2VASc score ≥1, of whom 54% were on warfarin. South Asian patients were at higher stroke risk than white patients (OR 1.67, 95% CI 1.02 to 2.73). Warfarin under-prescribing in people over 80 years of age persisted without improvement throughout 2008–2011. There were no clear differences in warfarin use by ethnic group. Conclusions Despite a reduced prevalence of AF among South Asian patients, their risk of stroke is higher than for white patients or black African/Caribbean patients in association with diabetes, cardiovascular disease, and hypertension. Under-prescription of anticoagulation persists in all ethnic groups, a deficit most pronounced in the elderly. Use of the CHA2DS2VASc score would enhance optimal management in primary care.