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Journal articleMassen G, Quint J, 2025,
The association between fibrotic diseases and treatment resistant hypertension in England
, European Journal of Preventive Cardiology -
Journal articleMorgan A, Massen GM, Whittaker HR, et al., 2025,
Commonly prescribed medications and risk of pneumonia and all-cause mortality in people with idiopathic pulmonary fibrosis: a UK population-based cohort study
, Pneumonia, Vol: 17, ISSN: 2200-6133Background A growing body of evidence suggests that prolonged use of inhaled corticosteroids (ICS) and proton pump inhibitors (PPIs) is associated with increased risks of pneumonia. A substantial proportion of people with idiopathic pulmonary fibrosis (IPF) are prescribed PPIs or ICS to treat common comorbidities, giving rise to concerns that use of these medications may be associated with potential harms in this patient population. Methods We used UK Clinical Practice Research Datalink (CPRD) Aurum primary care data linked to national mortality and hospital admissions data to create a cohort of people diagnosed with IPF on or after 1 January 2010. Patients were assigned to one of three exposure categories according to their prescribing history in the 12 months prior to IPF diagnosis as follows: “regular” users (≥4 prescriptions), “irregular” users (1–3 prescriptions) and “non-users” (no prescriptions). We explored the association between PPI/ICS prescription and pneumonia hospitalisation and all-cause mortality using multinomial Cox regression models. ResultsA total of 17,105 people met our study inclusion criteria; 62.6% were male and 15.9% were current smokers. Median age at IPF diagnosis was 76.7 years (IQR: 69.6–82.7). 19.9% were regularly prescribed PPIs, and 16.0% ICS, prior to IPF diagnosis. Regular prescribing of PPIs and ICS was positively associated with hospitalisation for pneumonia; the adjusted HR for pneumonia hospitalisation comparing regular PPI users with non-users was 1.14 (95%CI: 1.04–1.24); for regular ICS users the corresponding HR was 1.40 (95%CI: 1.25–1.55). We also observed a small increased risk for all-cause mortality in the “regular ICS user” group compared with the “non-user” control group (HRadj=1.19, 1.06–1.33). We found no evidence of an association between PPI prescribing and all-cause mortality. ConclusionProlonged prescription of medic
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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 articleMassen G, Quint J, 2024,
Using routinely collected electronic healthcare record data to investigate fibrotic multimorbidity in England
, Clinical Epidemiology, ISSN: 1179-1349 -
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 articleMassen GM, Stone PW, Kwok HHY, et al., 2024,
A review of codelists used to define hypertension in electronic health records and development of a codelist for research
, Open Heart, Vol: 11, ISSN: 2053-3624Background and aims Hypertension is a leading risk factor for cardiovascular disease. Electronic health records (EHRs) are routinely collected throughout a person’s care, recording all aspects of health status, including current and past conditions, prescriptions and test results. EHRs can be used for epidemiological research. However, there are nuances in the way conditions are recorded using clinical coding; it is important to understand the methods which have been applied to define exposures, covariates and outcomes to enable interpretation of study findings. This study aimed to identify codelists used to define hypertension in studies that use EHRs and generate recommended codelists to support reproducibility and consistency.Eligibility criteria Studies included populations with hypertension defined within an EHR between January 2010 and August 2023 and were systematically identified using MEDLINE and Embase. A summary of the most frequently used sources and codes is described. Due to an absence of Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) codelists in the literature, a recommended SNOMED CT codelist was developed to aid consistency and standardisation of hypertension research using EHRs.Findings 375 manuscripts met the study criteria and were eligible for inclusion, and 112 (29.9%) reported codelists. The International Classification of Diseases (ICD) was the most frequently used clinical terminology, 59 manuscripts provided ICD 9 codelists (53%) and 58 included ICD 10 codelists (52%). Informed by commonly used ICD and Read codes, usage recommendations were made. We derived SNOMED CT codelists informed by National Institute for Health and Care Excellence guidelines for hypertension management. It is recommended that these codelists be used to identify hypertension in EHRs using SNOMED CT codes.Conclusions Less than one-third of hypertension studies using EHRs included their codelists. Transparent methodology for codelist creation is
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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 articleMassen G, Quint J, 2024,
Using Routinely Collected Electronic Healthcare Record Data to Investigate Fibrotic Multimorbidity in England [Response to Letter]
, CLINICAL EPIDEMIOLOGY, Vol: 16, Pages: 657-658, ISSN: 1179-1349 -
Journal articleMassen GM, 2023,
Classifying the unclassifiable-a Delphi study to reach consensus on the fibrotic nature of diseases (vol 116, pg 429, 2023)
, QJM-AN INTERNATIONAL JOURNAL OF MEDICINE, Vol: 116, Pages: 824-824, ISSN: 1460-2725
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