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  • Journal article
    Graul E, Stone P, Massen G, Hatam S, Adamson A, Denaxas S, Peters N, Quint Jet 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: 2574-2531

    Objective: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.

  • Journal article
    Lenoir A, Whittaker H, Gayle A, Jarvis D, Quint Jet al., 2023,

    Mortality in non-exacerbating COPD: a longitudinal analysis of UK primary care data

    , Thorax, Vol: 78, Pages: 904-911, ISSN: 0040-6376

    Introduction: 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.

  • Journal article
    Whittaker H, Nordon C, Rubino A, Morris T, Xu Y, De Nigris E, Mullerova H, Quint Jet 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: 0040-6376

    ObjectiveLittle 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.

  • Journal article
    Massen 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 article
    Whittaker H, Quint J, Rothnie K, 2023,

    Cause specific mortality in COPD sub-populations: a cohort study of 339 647 people in England

    , Thorax, Pages: 1-7, ISSN: 0040-6376

    Background 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

  • Journal article
    Pikoula M, Kallis C, Madjiheurem S, Quint JK, Bafadhel M, Denaxas Set 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 article
    Massen GM, Allen RJ, Leavy OC, Selby NM, Aithal GP, Oliver N, Parfrey H, Wain LV, Jenkins G, Stewart I, Quint JK, DEMISTIFI consortiumet 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: 1460-2393

    BackgroundTraditionally, 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.

  • Journal article
    Stewart I, Molyneaux PL, Fabbri L, Quint JK, Walsh SLF, Weeks M, Jenkins RGet al., 2023,

    Residual lung abnormalities following COVID-19 hospitalization: interim analysis of the UKILD Post-COVID study

    , American Journal of Respiratory and Critical Care Medicine, Vol: 207, Pages: 693-703, ISSN: 1073-449X

    Rationale: Shared symptoms and genetic architecture between coronavirus disease (COVID-19) and lung fibrosis suggest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may lead to progressive lung damage.Objectives: The UK Interstitial Lung Disease Consortium (UKILD) post–COVID-19 study interim analysis was planned to estimate the prevalence of residual lung abnormalities in people hospitalized with COVID-19 on the basis of risk strata.Methods: The PHOSP–COVID-19 (Post-Hospitalization COVID-19) study was used to capture routine and research follow-up within 240 days from discharge. Thoracic computed tomography linked by PHOSP–COVID-19 identifiers was scored for the percentage of residual lung abnormalities (ground-glass opacities and reticulations). Risk factors in linked computed tomography were estimated with Bayesian binomial regression, and risk strata were generated. Numbers within strata were used to estimate posthospitalization prevalence using Bayesian binomial distributions. Sensitivity analysis was restricted to participants with protocol-driven research follow-up.Measurements and Main Results: The interim cohort comprised 3,700 people. Of 209 subjects with linked computed tomography (median, 119 d; interquartile range, 83–155), 166 people (79.4%) had more than 10% involvement of residual lung abnormalities. Risk factors included abnormal chest X-ray (risk ratio [RR], 1.21; 95% credible interval [CrI], 1.05–1.40), percent predicted DlCO less than 80% (RR, 1.25; 95% CrI, 1.00–1.56), and severe admission requiring ventilation support (RR, 1.27; 95% CrI, 1.07–1.55). In the remaining 3,491 people, moderate to very high risk of residual lung abnormalities was classified at 7.8%, and posthospitalization prevalence was estimated at 8.5% (95% CrI, 7.6–9.5), rising to 11.7% (95% CrI, 10.3–13.1) in the sensitivity analysis.Conclusions: Residual lung abnormalities were estimated in up to 11% of

  • Journal article
    Cook S, Schmedt N, Broughton J, Kalra PA, Tomlinson LA, Quint Jet al., 2023,

    Characterising the burden of chronic kidney disease among people with type 2 diabetes in England: a cohort study using the Clinical Practice Research Datalink

    , BMJ Open, Vol: 13, Pages: 1-13, ISSN: 2044-6055

    Objectives To describe prevalence of chronic kidney disease (CKD), demographic and clinical characteristics, treatment patterns and rates of cardiovascular and renal complications for patients with type 2 diabetes (T2D) treated in routine clinical care.Design Repeat cross-sectional study (6 monthly cross-sections) and cohort study from 1 January 2017 to 31 December 2019.Setting Primary care data from English practices contributing to the UK Clinical Practice Research Datalink linked to Hospital Episode Statistics and Office for National Statistics mortality data.Participants Patients with T2D aged >18 years, at least one year of registration data.Primary and secondary outcomes Primary outcome was prevalence of CKD defined as chronic kidney disease epidemiology collaboration (CKD-EPI) estimated glomerular filtration rate <60 mL/min/1.73 m2, and/or urinary albumin creatinine ratio ≥3 mg/mmol in the past 24 months. Secondary outcomes were prescriptions of medications of interest and clinical and demographic characteristics in the past 3 months.In the cohort study rates of renal and cardiovascular complications, all-cause mortality and hospitalisations over the study period were compared among those with and without CKD.Results There were 574 190 eligible patients with T2D as of 1 January 2017 and 664 296 as of 31 December 2019. Estimated prevalence of CKD across the study period was stable at approximately 30%. Medication use was stable over time in people with CKD and T2D, with low use of steroidal mineralocorticoid receptor antagonists (approximately 4.5% across all time points) and a low use but steady increase in use of sodium-glucose co-transporter-2 inhibitors (from 2.6% to 6.2%). Rates of all complications were higher in those with CKD at the start of the study period, with increasing rates, with increased severity of CKD, heart failure and albuminuria.Conclusions The burden of CKD in patients with T2D is high and asso

  • Journal article
    Morgan A, Maslova E, Kallis C, Sinha I, Roberts G, Tran TN, van der Valk RJP, Quint JKet al., 2023,

    Short-acting β<sub>2</sub>-agonists and exacerbations in children with asthma in England: SABINA Junior


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