Approach to record linkage of primary care data from Clinical Practice Research Datalink to other health-related patient data: overview and implications

Record linkage is increasingly used to expand the information available for public health research. An understanding of record linkage methods and the relevant strengths and limitations is important for robust analysis and interpretation of linked data. Here, we describe the approach used by Clinical Practice Research Datalink (CPRD) to link primary care data to other patient level datasets, and the potential implications of this approach for CPRD data analysis. General practice electronic health record software providers separately submit de-identified data to CPRD and patient identifiers to NHS Digital, excluding patients who have opted-out from contributing data. Data custodians for external datasets also send patient identifiers to NHS Digital. NHS Digital uses identifiers to link the datasets using an 8-stage deterministic methodology. CPRD subsequently receives a de-identified linked cohort file and provides researchers with anonymised linked data and metadata detailing the linkage process. This methodology has been used to generate routine primary care linked datasets, including data from Hospital Episode Statistics, Office for National Statistics and National Cancer Registration and Analysis Service. 10.6 million (M) patients from 411 English general practices were included in record linkage in June 2018. 9.1M (86%) patients were of research quality, of which 8.0M (88%) had a valid NHS number and were eligible for linkage in the CPRD standard linked dataset release. Linking CPRD data to other sources improves the range and validity of research studies. This manuscript, together with metadata generated on match strength and linkage eligibility, can be used to inform study design and explore potential linkage-related selection and misclassification biases

Statin use in cancer survivors versus the general population: cohort study using primary care data from the UK clinical practice research datalink.

BACKGROUND: Cancer survivors may be at increased risk of cardiovascular diseases, but little is known about whether prescribing guidelines for the primary prevention of cardiovascular disease are adequately implemented in these patients. We compared levels of statin initiation and cessation among cancer survivors compared to the general population to determine differences in uptake of pharmaceutical cardiovascular risk prevention measures in these groups. METHODS: The study population included individuals aged ≥40 during 2005-13 within the UK Clinical Practice Research Datalink primary care database. Within this population we identified cancer survivors who were alive and under follow-up at least 1 year after diagnosis, and controls with no cancer history. Follow-up time prior to cancer diagnosis was included in the control cohort. Using logistic regression, we compared these groups with respect to uptake of statins within 1 month of a first high recorded cardiovascular risk score. Then, we used Cox modelling to compare persistence on statin therapy (time to statin cessation) between cancer survivors and controls from the main study population who had initiated on a statin. RESULTS: Among 4202 cancer survivors and 113,035 controls with a record indicating a high cardiovascular risk score, 23.0% and 23.5% respectively initiated a statin within 1 month (adjusted odds ratio 0.98 [91.8-1.05], p = 0.626). Cancer survivors appeared more likely to discontinue statin treatment than controls (adjusted hazard ratio 1.07 [1.01-1.12], p = 0.02). This greater risk of discontinuing was only evident after the first year of therapy (p-interaction < 0.001). INTERPRETATION: Although cardiovascular risk is thought to be higher in cancer survivors compared to the general population, cancer survivors were no more likely to receive statins, and marginally more likely to cease long-term therapy, than general population controls. There may be an opportunity to mitigate the suspected higher cardiovascular risk in the growing population of cancer survivors by improving uptake of lipid-lowering treatment and persistence on therapy

Structure and Decay Correlations of Two-Neutron Systems Beyond the Dripline

The two-neutron unbound systems of 16Be, 13Li, 10He, and 26O have been measured using the Modular Neutron Array (MoNA) and 4 Tm Sweeper magnet setup. The correlations of the 3-body decay for the 16Be and 13Li were extracted and demonstrated a strong correlated enhancement between the two neutrons. The measurement of the 10He ground state resonance from a 14Be(−2p2n) reaction provided insight into previous predictions that wavefunction of the entrance channel, projectile, can influence the observed decay energy spectrum for the unbound system. Lastly, the decay-in-target (DiT) technique was utilized to extract the lifetime of the 26O ground state. The measured lifetime of 4.5+1.1 −1.5 (stat.)±3(sys.) ps provides the first indication of two-neutron radioactivity

Women, anger, and aggression an interpretative phenomenological analysis

This study reports a qualitative phenomenological investigation of anger and anger-related aggression in the context of the lives of individual women. Semistructured interviews with five women are analyzed using interpretative phenomenological analysis. This inductive approach aims to capture the richness and complexity of the lived experience of emotional life. In particular, it draws attention to the context-dependent and relational dimension of angry feelings and aggressive behavior. Three analytic themes are presented here: the subjective experience of anger, which includes the perceptual confusion and bodily change felt by the women when angry, crying, and the presence of multiple emotions; the forms and contexts of aggression, paying particular attention to the range of aggressive strategies used; and anger as moral judgment, in particular perceptions of injustice and unfairness. The authors conclude by examining the analytic observations in light of phenomenological thinking

Microscopy techniques for determining water-cement (w/c) ratio in hardened concrete: A round-robin assessment

Water to cement (w/c) ratio is usually the most important parameter specified in concrete design and is sometimes the subject of dispute when a shortfall in concrete strength or durability is an issue. However, determination of w/c ratio in hardened concrete by testing is very difficult once the concrete has set. This paper presents the results from an inter-laboratory round-robin study organised by the Applied Petrography Group to evaluate and compare microscopy methods for measuring w/c ratio in hardened concrete. Five concrete prisms with w/c ratios ranging from 0.35 to 0.55, but otherwise identical in mix design were prepared independently and distributed to 11 participating petrographic laboratories across Europe. Participants used a range of methods routine to their laboratory and these are broadly divided into visual assessment, measurement of fluorescent intensity and quantitative backscattered electron microscopy. Some participants determined w/c ratio using more than one method or operator. Consequently, 100 individual w/c ratio determinations were collected, representing the largest study of its type ever undertaken. The majority (81%) of the results are accurate to within ± 0.1 of the target mix w/c ratios, 58% come to within ± 0.05 and 37% are within ± 0.025. The study shows that microscopy-based methods are more accurate and reliable compared to the BS 1881-124 physicochemical method for determining w/c ratio. The practical significance, potential sources of errors and limitations are discussed with the view to inform future applications

Cancer history as a predictor in cardiovascular risk scores: a primary care cohort study.

BACKGROUND: Cardiovascular risks are raised in cancer survivors but cancer history is not included in cardiovascular risk scores that inform preventive decisions. AIM: To assess whether cancer diagnosis should be included in cardiovascular risk scores. DESIGN AND SETTING: Cohort study using data from English general practices linked to hospital, cancer registration, and death registration data from 1990 to 2015. METHOD: Adults alive 1 year after a first cancer diagnosis and age, sex, general practice, and calendar- time matched cancer-free individuals were included. Individuals with 10% relative difference with P<0.01) was assessed. RESULTS: In total, 81 420 cancer survivors and 413 547 cancer-free individuals were followed for a median 5.2 years (interquartile range [IQR] 2.8- 9.1) and 6.3 years (IQR 3.5-10.2), respectively. Including a 1-year cancer survivorship variable in a QRISK3-based model met the threshold for inclusion for males (independent hazard ratio [iHR] 1.16, 95% confidence interval [CI] = 1.11 to 1.20, P<0.001) but not females (iHR 1.07, 95% CI = 1.01 to 1.14, P = 0.02). When including cancer type, the threshold was met for both sexes with history of haematological cancer (males: iHR 1.27, 95% CI = 1.16 to 1.40, P <0.001; females: iHR 1.59, 95% CI = 1.32 to 1.91, P<0.001) and for males but not females with history of solid cancers (males: iHR 1.13, 95% CI = 1.08 to 1.18, P <0.001; females: iHR 1.04, 95% CI = 0.98 to 1.10, P = 0.19). CONCLUSION: Developers should consider including cancer history variables in future cardiovascular risk models

Does Cardiovascular Mortality Overtake Cancer Mortality During Cancer Survivorship?: An English Retrospective Cohort Study.

Background: Cancer survivors have a higher risk for developing cardiovascular diseases than the general population. Objectives: The aim of this study was to investigate whether cardiovascular mortality overtakes cancer-specific mortality during cancer survivorship and, if so, at what point cardiovascular disease becomes the dominant cause of death. Methods: This cohort study used linked English electronic health records, including death registration data. The study population included 104,028 adults ≥40 years of age whose first cancer diagnosis was for 1 of 9 common cancers and who were alive and followed up at least 1 year after diagnosis. Age-stratified mortality rates were estimated from cardiovascular disease or cancer by predicting from Poisson models incorporating categorical age at diagnosis and time since diagnosis. Where cardiovascular disease mortality overtook cancer mortality, the crossover point was estimated using interpolation. Results: Mortality from cardiovascular causes overtook mortality due to the primary cancer at 2 to 11 years after cancer diagnosis in survivors of all 9 cancer types ≥80 years of age at diagnosis and after 5 to 17 years in survivors of 7 cancer types 60 to 79 years of age at diagnosis. Cardiovascular mortality overtook all cancer mortality for 6 and 2 cancer sites in the ≥80-year and 60- to 79-year age groups, respectively, over a longer time period. Cardiovascular mortality did not overtake cancer mortality during the observation period in patients aged 40 to 59 years, except among survivors of uterine cancer. Conclusions: In older survivors of 9 common cancers, cardiovascular mortality becomes dominant over mortality from the primary cancer, though not always over total cancer mortality, as time passes since cancer diagnosis

Indirect acute effects of the COVID-19 pandemic on physical and mental health in the UK: a population-based study.

BACKGROUND: There are concerns that the response to the COVID-19 pandemic in the UK might have worsened physical and mental health, and reduced use of health services. However, the scale of the problem is unquantified, impeding development of effective mitigations. We aimed to ascertain what has happened to general practice contacts for acute physical and mental health outcomes during the pandemic. METHODS: Using de-identified electronic health records from the Clinical Research Practice Datalink (CPRD) Aurum (covering 13% of the UK population), between 2017 and 2020, we calculated weekly primary care contacts for selected acute physical and mental health conditions: anxiety, depression, self-harm (fatal and non-fatal), severe mental illness, eating disorder, obsessive-compulsive disorder, acute alcohol-related events, asthma exacerbation, chronic obstructive pulmonary disease exacerbation, acute cardiovascular events (cerebrovascular accident, heart failure, myocardial infarction, transient ischaemic attacks, unstable angina, and venous thromboembolism), and diabetic emergency. Primary care contacts included remote and face-to-face consultations, diagnoses from hospital discharge letters, and secondary care referrals, and conditions were identified through primary care records for diagnoses, symptoms, and prescribing. Our overall study population included individuals aged 11 years or older who had at least 1 year of registration with practices contributing to CPRD Aurum in the specified period, but denominator populations varied depending on the condition being analysed. We used an interrupted time-series analysis to formally quantify changes in conditions after the introduction of population-wide restrictions (defined as March 29, 2020) compared with the period before their introduction (defined as Jan 1, 2017 to March 7, 2020), with data excluded for an adjustment-to-restrictions period (March 8-28). FINDINGS: The overall population included 9 863 903 individuals on Jan 1, 2017, and increased to 10 226 939 by Jan 1, 2020. Primary care contacts for almost all conditions dropped considerably after the introduction of population-wide restrictions. The largest reductions were observed for contacts for diabetic emergencies (odds ratio 0·35 [95% CI 0·25-0·50]), depression (0·53 [0·52-0·53]), and self-harm (0·56 [0·54-0·58]). In the interrupted time-series analysis, with the exception of acute alcohol-related events (0·98 [0·89-1·10]), there was evidence of a reduction in contacts for all conditions (anxiety 0·67 [0·66-0·67], eating disorders 0·62 [0·59-0·66], obsessive-compulsive disorder [0·69 [0·64-0·74]], self-harm 0·56 [0·54-0·58], severe mental illness 0·80 [0·78-0·83], stroke 0·59 [0·56-0·62], transient ischaemic attack 0·63 [0·58-0·67], heart failure 0·62 [0·60-0·64], myocardial infarction 0·72 [0·68-0·77], unstable angina 0·72 [0·60-0·87], venous thromboembolism 0·94 [0·90-0·99], and asthma exacerbation 0·88 [0·86-0·90]). By July, 2020, except for unstable angina and acute alcohol-related events, contacts for all conditions had not recovered to pre-lockdown levels. INTERPRETATION: There were substantial reductions in primary care contacts for acute physical and mental conditions following the introduction of restrictions, with limited recovery by July, 2020. Further research is needed to ascertain whether these reductions reflect changes in disease frequency or missed opportunities for care. Maintaining health-care access should be a key priority in future public health planning, including further restrictions. The conditions we studied are sufficiently severe that any unmet need will have substantial ramifications for the people with the conditions as well as health-care provision. FUNDING: Wellcome Trust Senior Fellowship, Health Data Research UK