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Journal articleMassen GM, Blamires O, Grainger M, et al., 2024,
UK electronic healthcare records for research: a scientometric analysis of respiratory, cardiovascular, and COVID-19 publications
, Pragmatic and Observational Research, Vol: 15, Pages: 151-164, ISSN: 1179-7266Background: Routinely collected electronic healthcare records (EHRs) document many details of a person’s health, including demographics, preventive services, symptoms, tests, disease diagnoses and prescriptions. Although not collected for research purposes, these data provide a wealth of information which can be incorporated into epidemiological investigations, and records can be analysed to understand a range of important health questions. We aimed to understand the use of routinely collected health data in epidemiological studies relating to three of the most common chronic respiratory conditions, namely: asthma, chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). We also characterised studies using EHR data to investigate respiratory diseases more generally, relative to cardiovascular disease and COVID-19, to understand trends in the use of these data.Methods: We conducted a search of the Scopus database, to identify original research articles (irrespective of date) which used data from one of the following most frequently used UK EHR databases: Clinical Practice Research Datalink (including General Practice Research Database (CPRD’s predecessor)), The Health Improvement Network and QResearch, defined through the presence of keywords. These databases were selected as they had been previously included in the works of Vezyridis and Timmons.Findings: A total of 716 manuscripts were included in the analysis of the three chronic respiratory conditions. The majority investigated either asthma or COPD, whilst only 28 manuscripts investigated ILD. The number of publications has increased for respiratory conditions over the past 10 years (888% increase from 2000 to 2022) but not as much as for cardiovascular diseases (1105%). These data have been used to investigate comorbidities, off-target effects of medication, as well as assessing disease incidence and prevalence. Most papers published across all three domains were in journals
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Journal articleGraul E, Nordon C, Rhodes K, et al., 2024,
Factors associated with non-fatal heart failure and atrial fibrillation or flutter within the first 30 days post COPD exacerbation: a nested case-control study
, BMC Pulmonary Medicine, Vol: 24, ISSN: 1471-2466BackgroundAn immediate, temporal risk of heart failure and arrhythmias after a Chronic Obstructive Pulmonary Disease (COPD) exacerbation has been demonstrated, particularly in the first month post-exacerbation. However, the clinical profile of patients who develop heart failure (HF) or atrial fibrillation/flutter (AF) following exacerbation is unclear. Therefore we examined factors associated with people being hospitalized for HF or AF, respectively, following a COPD exacerbation.MethodsWe conducted two nested case-control studies, using primary care electronic healthcare records from the Clinical Practice Research Datalink Aurum linked to Hospital Episode Statistics, Office for National Statistics for mortality, and socioeconomic data (2014-2020). Cases had hospitalization for HF or AF within 30 days of a COPD exacerbation, with controls matched by GP practice (HF 2:1;AF 3:1). We used conditional logistic regression to explore demographic and clinical factors associated with HF and AF hospitalization.ResultsOdds of HF hospitalization (1,569 cases, 3,138 controls) increased with age, type II diabetes, obesity, HF and arrhythmia history, exacerbation severity (hospitalization), most cardiovascular medications, GOLD airflow obstruction, MRC dyspnea score, and chronic kidney disease. Strongest associations were for severe exacerbations (adjusted odds ratio (aOR)=6.25, 95%CI 5.10-7.66), prior HF (aOR=2.57, 95%CI 1.73-3.83), age≥80 years (aOR=2.41, 95%CI 1.88-3.09), and prior diuretics prescription (aOR=2.81, 95%CI 2.29-3.45).Odds of AF hospitalization (841 cases, 2,523 controls) increased with age, male sex, severe exacerbation, arrhythmia and pulmonary hypertension history and most cardiovascular medications. Strongest associations were for severe exacerbations (aOR=5.78, 95%CI 4.45-7.50), age≥80 years (aOR=3.15, 95%CI 2.26-4.40), arrhythmia (aOR=3.55, 95%CI 2.53-4.98), pulmonary hypertension (aOR=3.05, 95%CI 1.21-7.68), and prescription of anticoagulants (aOR=3.
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Journal articleGraul E, Nordon C, Rhodes K, et al., 2024,
Temporal risk of nonfatal cardiovascular events after chronic obstructive pulmonary disease exacerbation: a population-based study
, American Journal of Respiratory and Critical Care Medicine, Vol: 209, Pages: 960-972, ISSN: 1073-449XRationale: Cardiovascular events following COPD exacerbations are recognised. Studies to date have been post-hoc analyses of trials, did not differentiate exacerbation severity, included death in the cardiovascular outcome, or had insufficient power to explore individual outcomes temporally. Objectives: We explore temporal relationships between moderate and severe exacerbations with incident, non-fatal hospitalised cardiovascular events, in a primary care-derived COPD cohort. Methods: We included people with COPD in England from 2014-2020, using Clinical Practice Research Datalink(CPRD) Aurum primary care database. Index date was first COPD exacerbation, or for those without exacerbation, date upon eligibility. We determined composite and individual cardiovascular events (acute coronary syndrome, arrhythmia, heart failure, ischaemic stroke, pulmonary hypertension) from linked hospital data. Adjusted Cox Regression models estimated average and time-stratified hazard ratios(aHR). Measurements and Main Results: Among 213,466 patients, 146,448 (68.6%) had any exacerbation;119,124 (55.8%) moderate exacerbation and 27,324 (12.8%) a severe exacerbation. 40,773 cardiovascular events were recorded. There was an immediate period of cardiovascular relative rate post any exacerbation (1-14 days,aHR=3.19,95%CI 2.71-3.76), followed by progressively declining yet maintained effects, elevated after one year(aHR=1.84,1.78-1.91). HRs were highest 1-14 days following severe exacerbations (aHR=14.5,12.2-17.3) but highest 14-30 days following moderate exacerbations (aHR=1.94,1.63-2.31). Cardiovascular outcomes with greatest two-week effects post severe exacerbation were arrhythmia (aHR=12.7,10.3-15.7) and heart failure (aHR=8.31,6.79-10.2). Conclusions: Cardiovascular events following moderate exacerbations occur slightly later than severe exacerbations; heightened relative rates remain beyond one year irrespective of severity. The period immediately following exacerbation presents a cr
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Journal articleWhittaker H, Quint J, Rothnie K, 2024,
Cause specific mortality in COPD sub-populations: a cohort study of 339 647 people in England
, Thorax, Vol: 79, Pages: 202-208, ISSN: 0040-6376Background Identifying correlates of cause-specific mortality in patients with chronic obstructive pulmonary disease (COPD) may aid the targeting of therapies to reduce mortality. We determined factors associated with causes of death in a primary care COPD population.Methods Clinical Practice Research Datalink Aurum was linked to Hospital Episode Statistics and death certificate data. People with COPD alive between 1 January 2010 and 1 January 2020 were included. Patient characteristics were defined before the start of follow-up: (a) frequency and severity of exacerbations; (b) emphysema or chronic bronchitis; (c) Global Obstructive Lung Disease (GOLD) groups A–D; and (d) airflow limitation. We used Cox Proportional Hazards regression and competing risks to investigate the association between patient characteristics and risk of all-cause, COPD and cardiovascular (CV) mortality.Results 339 647 people with COPD were included of which 97 882 died during follow-up (25.7% COPD related and 23.3% CV related). Airflow limitation, GOLD group, exacerbation frequency and severity, and COPD phenotype were associated with all-cause mortality. Exacerbations, both increased frequency and severity, were associated with COPD-related mortality (≥2 exacerbations vs none adjusted HR: 1.64, 1.57–1.71; 1 severe vs none adjusted HR: 2.17, 2.04–2.31, respectively). Patients in GOLD groups B–D had a higher risk of COPD and CV mortality compared with GOLD group A (GOLD group D vs group A, adjusted HR for COPD mortality: 4.57, 4.23–4.93 and adjusted HR for CV mortality: 1.53, 1.41–1.65). Increasing airflow limitation was also associated with both COPD and CV mortality (GOLD 4 vs 1, adjusted HR: 12.63, 11.82–13.51 and adjusted HR: 1.75, 1.60–1.91, respectively).Conclusion Poorer airflow limitation, worse functional status and exacerbations had substantial associations with risk of all-cause mortality. Differing results for CV and
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Journal articleGraul E, Stone P, Massen G, et al., 2023,
Determining prescriptions in electronic healthcare record data: methods for development of standardized, reproducible drug codelists
, JAMIA Open, Vol: 6, Pages: 1-11, ISSN: 2574-2531Objective:To develop a standardizable, reproducible method for creating drug codelists that incorporates clinical expertise and is adaptable to other studies and databases. Materials and Methods: We developed methods to generate drug codelists and tested this using the Clinical Practice Research Datalink (CPRD) Aurum database. accounting for missing data in the database. We generated codelists for 1) cardiovascular disease and 2) inhaled Chronic Obstructive Pulmonary Disease (COPD) therapies, applying them to a sample cohort of 335,931 COPD patients. We compared comprehensively searching on all search variables (A) to B) chemical and C) ontological information only.Results: In Search A we determined 165,150 patients prescribed cardiovascular drugs(49.2% of cohort), and 317,963 prescribed COPD inhalers (94.7% of cohort). Considering output per value set, Search C missed substantial prescriptions, including vasodilator anti-hypertensives (A and B:19,696 prescriptions; C:1,145) and SAMA inhalers (A and B:35,310; C:564).Discussion: We recommend the full methods (A) for comprehensiveness. There are special considerations when generating adaptable and generalizable drug codelists, including fluctuating status, cohort-specific drug indications, underlying hierarchical ontology, and statistical analyses. Conclusions: Methods must have end-to-end clinical input, and be standardizable, reproducible, and understandable to all researchers across data contexts.
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Journal articleLenoir A, Whittaker H, Gayle A, et al., 2023,
Mortality in non-exacerbating COPD: a longitudinal analysis of UK primary care data
, Thorax, Vol: 78, Pages: 904-911, ISSN: 0040-6376Introduction: Non-exacerbating patients with chronic obstructive pulmonary disease (COPD) are a less studied phenotype. We investigated clinical characteristics, mortality rates and causes of death among non-exacerbating compared with exacerbating patients with COPD.Methods: We used data from the Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics between 1 January 2004 and 31 December 2018. Ever smokers with a COPD diagnosis with minimum 3 years of baseline information were included. We compared overall using Cox regression and cause-specific mortality rates using competing risk analysis, adjusted for age, sex, deprivation, smoking status, body mass index, GOLD stage and comorbidities. Causes of death were identified using International Classification of Diseases-10 codes.Results: Among 67 516 patients, 17.3% did not exacerbate during the 3-year baseline period. Mean follow-up was 4 years. Non-exacerbators were more likely to be male (63.3% vs 52.4%, p<0.001) and less often had a history of asthma (33.9% vs 43.6%, p<0.001) or FEV1<50% predicted (23.7 vs 31.8%) compared with exacerbators. Adjusted HR for overall mortality in non-exacerbators compared with exacerbators was 0.62 (95% CI 0.56 to 0.70) in the first year of follow-up and 0.87 (95% CI 0.83 to 0.91) thereafter. Non-exacerbating patients with COPD died less of respiratory causes than exacerbators (29.2% vs 40.3%) and more of malignancies (29.4% vs 23.4%) and cardiovascular diseases (26.2% vs 22.9%). HRs for malignant and circulatory causes of death were increased after the first year of follow-up.Discussion: In this primary care cohort, non-exacerbators showed distinct clinical characteristics and lower mortality rates. Non-exacerbators were equally likely to die of respiratory, malignant or cardiovascular diseases.
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Journal articleWhittaker H, Nordon C, Rubino A, et al., 2023,
Frequency and severity of respiratory infections prior to COPD diagnosis and risk of subsequent post-diagnosis COPD exacerbations and mortality: EXACOS-UK health care data study
, Thorax, Vol: 78, Pages: 760-766, ISSN: 0040-6376ObjectiveLittle is known about how lower respiratory tract infections (LRTIs) before chronic obstructive pulmonary disease (COPD) are associated with future exacerbations and mortality. We investigated this association in COPD patients in England. MethodsClinical Practice Research Datalink Aurum, Hospital Episode Statistics, and Office of National Statistics data were used. Start of follow-up was patient’s first ever COPD diagnosis date and a 1-year baseline period prior to start of follow-up was used to find mild LRTIs (GP events/no antibiotics), moderate LRTIs (GP events +antibiotics), and severe LRTIs (hospitalised). Patients were categorised as having: none, 1 mild only, 2+ mild only, 1 moderate, 2+ moderate, and 1+ severe. Negative binomial regression modelled the association between baseline LRTIs and subsequent COPD exacerbations and Cox regression was used to investigate mortality. ResultsIn 215,234 COPD patients, increasing frequency and severity of mild and moderate LRTIs were associated with increased rates of subsequent exacerbations compared to no recorded LRTIs (1 mild adjusted IRR 1.16, 95%CI 1.14-1.18, 2+ mild IRR 1.51, 95%CI 1.46-1.55, 1 moderate IRR 1.81, 95%CI 1.78-1.85, 2+ moderate IRR 2.55, 95%CI 2.48-2.63). Patients with 1+ severe LRTI (vs. no baseline LRTIs) also showed an increased rate of future exacerbations (adjusted IRR 1.75, 95%CI, 1.70-1.80). This pattern of association was similar for risk of all-cause and COPD-related mortality however, patients with 1+ severe LRTIs had the highest risk of all-cause and COPD mortality. ConclusionIncreasing frequency and severity of LRTIs prior to COPD diagnosis were associated with increasing rates of subsequent exacerbations, and increasing risk all-cause and COPD-related mortality.
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Journal articleMassen GM, Stewart I, Quint JK, 2023,
Response to: Consensus and agreements on the classification of fibrotic diseases
, QJM: an international journal of medicine, ISSN: 1460-2393 -
Journal articlePikoula M, Kallis C, Madjiheurem S, et al., 2023,
Evaluation of data processing pipelines on real-world electronic health records data for the purpose of measuring patient similarity
, PLOS ONE, Vol: 18, ISSN: 1932-6203 -
Journal articleMassen GM, Allen RJ, Leavy OC, et al., 2023,
Classifying the unclassifiable – A Delphi study to reach consensus on the fibrotic nature of diseases
, QJM: an international journal of medicine, Vol: 116, Pages: 429-435, ISSN: 1460-2393BackgroundTraditionally, clinical research has focused on individual fibrotic diseases or fibrosis in a particular organ. However, it is possible for people to have multiple fibrotic diseases. While multi-organ fibrosis may suggest shared pathogenic mechanisms, yet there is no consensus on what constitutes a fibrotic disease and therefore fibrotic multimorbidity.AimA Delphi study was performed to reach consensus on which diseases may be described as fibrotic.MethodsParticipants were asked to rate a list of diseases, sub-grouped according to eight body regions, as ‘fibrotic manifestation always present’, ‘can develop fibrotic manifestations’, ‘associated with fibrotic manifestations’ or ‘not fibrotic nor associated’. Classifications of ‘fibrotic manifestation always present’ and ‘can develop fibrotic manifestations’ were merged and termed ‘fibrotic’. Clinical consensus was defined according to the interquartile range, having met a minimum number of responses. Clinical agreement was used for classification where diseases did not meet the minimum number of responses (required for consensus measure), were only classified if there was 100% consensus on disease classification.ResultsAfter consulting experts, searching the literature and coding dictionaries, a total of 323 non-overlapping diseases which might be considered fibrotic were identified; 92 clinical specialists responded to the first round of the survey. Over three survey rounds, 240 diseases were categorized as fibrotic via clinical consensus and 25 additional diseases through clinical agreement.ConclusionUsing a robust methodology, an extensive list of diseases was classified. The findings lay the foundations for studies estimating the burden of fibrotic multimorbidity, as well as investigating shared mechanisms and therapies.
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