Publications by authors named "Jennifer K Quint"

139 Publications

Association of Chronic Obstructive Pulmonary Disease with Morbidity and Mortality in Patients with Peripheral Artery Disease: Insights from the EUCLID Trial.

Int J Chron Obstruct Pulmon Dis 2021 29;16:841-851. Epub 2021 Mar 29.

Department of Medicine, Duke University Medical Center, Durham, NC, USA.

Background: Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of developing lower extremity peripheral artery disease (PAD) and suffering PAD-related morbidity and mortality. However, the effect and burden of COPD on patients with PAD is less well defined. This post hoc analysis from EUCLID aimed to analyze the risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with PAD and concomitant COPD compared with those without COPD, and to describe the adverse events specific to patients with COPD.

Methods: EUCLID randomized 13,885 patients with symptomatic PAD to monotherapy with either ticagrelor or clopidogrel for the prevention of MACE. In this analysis, MACE, MALE, mortality, and adverse events were compared between groups with and without COPD using unadjusted and adjusted Cox proportional hazards model.

Results: Of the 13,883 patients with COPD status available at baseline, 11% (n=1538) had COPD. Patients with COPD had a higher risk of MACE (6.02 vs 4.29 events/100 patient-years; p<0.001) due to a significantly higher risk of myocardial infarction (MI) (3.55 vs 1.85 events/100 patient-years; p<0.001) when compared with patients without COPD. These risks persisted after adjustment (MACE: adjusted hazard ratio (aHR) 1.30, 95% confidence interval [CI] 1.11-1.52; p<0.001; MI: aHR 1.45, 95% CI 1.18-1.77; p<0.001). However, patients with COPD did not have an increased risk of MALE or major bleeding. Patients with COPD were more frequently hospitalized for dyspnea and pneumonia (2.66 vs 0.9 events/100 patient-years; aHR 2.77, 95% CI 2.12-3.63; p<0.001) and more frequently discontinued study drug prematurely (19.36 vs 12.54 events/100 patient-years; p<0.001; aHR 1.34, 95% CI 1.22-1.47; p<0.001).

Conclusion: In patients with comorbid PAD and COPD, the risks of MACE, respiratory-related adverse events, and premature study drug discontinuation were higher when compared with patients without COPD.

Registration: ClinicalTrials.gov: NCT01732822.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/COPD.S292978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018572PMC
March 2021

Impact of COVID-19 national lockdown on asthma exacerbations: interrupted time-series analysis of English primary care data.

Thorax 2021 Mar 29. Epub 2021 Mar 29.

Asthma UK Centre for Applied Research, Centre for Medical Informatics, Usher Institute, The University of Edinburgh, Edinburgh, UK.

Background: The impact of COVID-19 and ensuing national lockdown on asthma exacerbations is unclear.

Methods: We conducted an interrupted time-series (lockdown on 23 March 2020 as point of interruption) analysis in asthma cohort identified using a validated algorithm from a national-level primary care database, the Optimum Patient Care Database. We derived asthma exacerbation rates for every week and compared exacerbation rates in the period: January to August 2020 with a pre-COVID-19 period and January to August 2016-2019. Exacerbations were defined as asthma-related hospital attendance/admission (including accident and emergency visit), or an acute course of oral corticosteroids with evidence of respiratory review, as recorded in primary care. We used a generalised least squares modelling approach and stratified the analyses by age, sex, English region and healthcare setting.

Results: From a database of 9 949 387 patients, there were 100 165 patients with asthma who experienced at least one exacerbation during 2016-2020. Of 278 996 exacerbation episodes, 49 938 (17.9%) required hospital visit. Comparing pre-lockdown to post-lockdown period, we observed a statistically significant reduction in the level (-0.196 episodes per person-year; p<0.001; almost 20 episodes for every 100 patients with asthma per year) of exacerbation rates across all patients. The reductions in level in stratified analyses were: 0.005-0.244 (healthcare setting, only those without hospital attendance/admission were significant), 0.210-0.277 (sex), 0.159-0.367 (age), 0.068-0.590 (region).

Conclusions: There has been a significant reduction in attendance to primary care for asthma exacerbations during the pandemic. This reduction was observed in all age groups, both sexes and across most regions in England.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/thoraxjnl-2020-216512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011425PMC
March 2021

The Utilization and Safety of Umeclidinium and Umeclidinium/Vilanterol in UK Primary Care: A Retrospective Cohort Study.

Int J Chron Obstruct Pulmon Dis 2021 10;16:629-642. Epub 2021 Mar 10.

Respiratory Epidemiology, GSK, Brentford, Middlesex, UK.

Background: Umeclidinium bromide (UMEC) and umeclidinium/vilanterol (UMEC/VI) received European approval for maintenance treatment of patients with chronic obstructive pulmonary disease (COPD) in 2014. This study examined prescribing patterns, possible off-label prescribing, potential safety-related outcomes and adherence of these medications in routine clinical practice post-approval.

Methods: This retrospective, multi-database, longitudinal observational study of new users of UMEC, UMEC/VI, or other long-acting bronchodilators (LABD) analyzed data from UK electronic health record databases (primary care cohort), linked to hospital data (linked cohort). Off-label prescribing, safety outcomes (cardiovascular, respiratory, and mortality), treatment patterns, and medication adherence were assessed.

Results: In the primary care cohort (new users of UMEC n=3875; UMEC/VI n=2224; other LABD n=32,809), two-thirds of UMEC users were prescribed concomitant inhaled corticosteroids/long-acting β-agonists. Possible off-label prescribing, defined as use in patients without COPD, was similar for UMEC (7.0%) and UMEC/VI (8.8%), but higher for new users of other LABD (18.0%). There were 547 UMEC users and 512 UMEC/VI users in the linked cohort. In both cohorts, incidence rates (IRs) of cardiovascular outcomes were similar for UMEC and UMEC/VI users (myocardial infarction IR per 1000 person-years [95% CIs]: UMEC 6.9 [4.4, 10.2]; UMEC/VI 6.8 [3.5, 11.9]). IRs of pneumonia and acute COPD exacerbations (AECOPD) were slightly higher among UMEC users compared with UMEC/VI users (AECOPD IR per 1000 person-years [95% CIs]: UMEC 979 [931, 1030]; UMEC/VI 746 [687, 811]). Adherence (medication possession ratio ≥80%) was 64% for UMEC and UMEC/VI.

Conclusion: Most new users of UMEC were receiving multiple-inhaler triple therapy. Off-label prescribing was uncommon for new users of UMEC and UMEC/VI. Incidence of cardiovascular and respiratory outcomes was as expected for these drug classes. This study provides evidence that UMEC and UMEC/VI are being prescribed appropriately and their safety profile remains unchanged.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/COPD.S291931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956862PMC
March 2021

Effectiveness and Safety of COPD Maintenance Therapy with Tiotropium/Olodaterol versus LABA/ICS in a US Claims Database.

Adv Ther 2021 Mar 15. Epub 2021 Mar 15.

Pneumology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute de Recerca (VHIR), Barcelona, Spain.

Introduction: In patients with chronic obstructive pulmonary disease (COPD), treatment with long-acting muscarinic antagonist (LAMA)/long-acting β-agonist (LABA) combination therapy significantly improves lung function versus LABA/inhaled corticosteroid (ICS). To investigate whether LAMA/LABA could provide better clinical outcomes than LABA/ICS, this non-interventional database study assessed the risk of COPD exacerbations, pneumonia, and escalation to triple therapy in patients with COPD initiating maintenance therapy with tiotropium/olodaterol versus any LABA/ICS combination.

Methods: Administrative healthcare claims and laboratory results data from the US HealthCore Integrated Research Database were evaluated for patients with COPD initiating tiotropium/olodaterol versus LABA/ICS treatment (January 2013-March 2019). Patients were aged at least 40 years with a diagnosis of COPD (but not asthma) at cohort entry. A Cox proportional hazard regression model was used (as-treated analysis) to assess risk of COPD exacerbation, community-acquired pneumonia, and escalation to triple therapy, both individually and as a combined risk of any one of these events. Potential imbalance of confounding factors between cohorts was handled using fine stratification, reweighting, and trimming by exposure propensity score (high-dimensional); subgroup analyses were conducted on the basis of blood eosinophil levels and exacerbation history.

Results: The total population consisted of 61,985 patients (tiotropium/olodaterol n = 2684; LABA/ICS n = 59,301); after reweighting, the total was 42,953 patients (tiotropium/olodaterol n = 2600; LABA/ICS n = 40,353; mean age 65 years; female 54.5%). Patients treated with tiotropium/olodaterol versus LABA/ICS experienced a reduction in the risk of COPD exacerbations (adjusted hazard ratio 0.76 [95% confidence interval 0.68, 0.85]), pneumonia (0.74 [0.57, 0.97]), escalation to triple therapy (0.22 [0.19, 0.26]), and any one of these events (0.45 [0.41, 0.49]); the combined risk was similar irrespective of baseline eosinophils and exacerbation history.

Conclusions: In patients with COPD, tiotropium/olodaterol was associated with a lower risk of COPD exacerbations, pneumonia, and escalation to triple therapy versus LABA/ICS, both individually and in combination; the combined risk was reduced irrespective of baseline eosinophils or exacerbation history.

Trial Registration: ClinicalTrials.gov identifier, NCT04138758 (registered 23 October 2019).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12325-021-01646-5DOI Listing
March 2021

UK prevalence of underlying conditions which increase the risk of severe COVID-19 disease: a point prevalence study using electronic health records.

BMC Public Health 2021 03 11;21(1):484. Epub 2021 Mar 11.

NIHR Health Protection Research Unit (HPRU) in Immunisation, London, UK.

Background: Characterising the size and distribution of the population at risk of severe COVID-19 is vital for effective policy and planning. Older age, and underlying health conditions, are associated with higher risk of death from COVID-19. This study aimed to describe the population at risk of severe COVID-19 due to underlying health conditions across the United Kingdom.

Methods: We used anonymised electronic health records from the Clinical Practice Research Datalink GOLD to estimate the point prevalence on 5 March 2019 of the at-risk population following national guidance. Prevalence for any risk condition and for each individual condition is given overall and stratified by age and region with binomial exact confidence intervals. We repeated the analysis on 5 March 2014 for full regional representation and to describe prevalence of underlying health conditions in pregnancy. We additionally described the population of cancer survivors, and assessed the value of linked secondary care records for ascertaining COVID-19 at-risk status.

Results: On 5 March 2019, 24.4% of the UK population were at risk due to a record of at least one underlying health condition, including 8.3% of school-aged children, 19.6% of working-aged adults, and 66.2% of individuals aged 70 years or more. 7.1% of the population had multimorbidity. The size of the at-risk population was stable over time comparing 2014 to 2019, despite increases in chronic liver disease and diabetes and decreases in chronic kidney disease and current asthma. Separately, 1.6% of the population had a new diagnosis of cancer in the past 5 y.

Conclusions: The population at risk of severe COVID-19 (defined as either aged ≥70 years, or younger with an underlying health condition) comprises 18.5 million individuals in the UK, including a considerable proportion of school-aged and working-aged individuals. Our national estimates broadly support the use of Global Burden of Disease modelled estimates in other countries. We provide age- and region- stratified prevalence for each condition to support effective modelling of public health interventions and planning of vaccine resource allocation. The high prevalence of health conditions among older age groups suggests that age-targeted vaccination strategies may efficiently target individuals at higher risk of severe COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12889-021-10427-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948667PMC
March 2021

The Impact of the Covid-19 Pandemic on Uptake of Influenza Vaccine: A UK-Wide Observational Study.

JMIR Public Health Surveill 2021 Feb 18. Epub 2021 Feb 18.

National Heart & Lung Institute, Imperial College London, Hammersmith Hospital CampusDu Cane Road, London, GB.

Background: In the face of the Covid-19 pandemic, the UK National Health Service (NHS) flu vaccination eligibility is extended this season to ~32.4 million (48.8%) of the population. Knowing intended uptake will inform supply and public health messaging to maximise vaccination.

Objective: The objective of this study was to measure the impact of the Covid-19 pandemic on acceptance of flu vaccination in the 2020-21 season, specifically focusing on those previously eligible who routinely decline vaccination and the newly eligible.

Methods: Intention to receive influenza vaccine in 2020-21 was asked of all registrants of the NHS's largest electronic personal health record by online questionnaire on 31st July 2020. Of those who were either newly or previously eligible but had not previously received influenza vaccination, multivariable logistic regression and network diagrams were used to examine reasons to have or decline vaccination.

Results: Among 6,641 respondents, 945 (14.2%) were previously eligible but not vaccinated, of whom 536 (56.7%) intended to receive flu vaccination in 2020/21, as did 466 (68.6%) of the newly eligible. Intention to receive the flu vaccine was associated with increased age, index of multiple deprivation (IMD) quintile, and considering oneself at high risk from Covid-19. Among those eligible but intending not to be vaccinated in 2020/21, 164 (30.2%) gave misinformed reasons. 47 (49.9%) of previously unvaccinated healthcare workers would decline vaccination in 2020/21.

Conclusions: In this sample, Covid-19 has increased acceptance of flu vaccination in those previously eligible but unvaccinated and motivates substantial uptake in the newly eligible. This study is essential for informing resource planning and the need for effective messaging campaigns to address negative misconceptions, also necessary for Covid-19 vaccination programmes.

Clinicaltrial: Not applicable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/26734DOI Listing
February 2021

Standardisation of Clinical Assessment, Management and Follow-Up of Acute Hospitalised Exacerbation of COPD: A Europe-Wide Consensus.

Int J Chron Obstruct Pulmon Dis 2021 16;16:321-332. Epub 2021 Feb 16.

Respiratory Medicine Unit, Nuffield Department of Medicine - Experimental Medicine, University of Oxford, Oxford, UK.

Background: Despite hospitalization for exacerbation being a high-risk event for morbidity and mortality, there is little consensus globally regarding the assessment and management of hospitalised exacerbations of COPD. We aimed to establish a consensus list of symptoms, physiological measures, clinical scores, patient questionnaires and investigations to be obtained at time of hospitalised COPD exacerbation and follow-up.

Methods: A modified Delphi online survey with pre-defined consensus of importance, feasibility and frequency of measures at hospitalisation and follow-up of a COPD exacerbation was undertaken.

Findings: A total of 25 COPD experts from 18 countries contributed to all 3 rounds of the survey. Experts agreed that a detailed history and examination were needed. Experts also agreed on which treatments are needed and how soon these should be delivered. Experts recommended that a full blood count, renal function, C-reactive protein and cardiac blood biomarkers (BNP and troponin) should be measured within 4 hours of admission and that the modified Medical Research Council dyspnoea scale (mMRC) and COPD assessment test (CAT) should be performed at time of exacerbation and follow-up. Experts encouraged COPD clinicians to strongly consider discussing palliative care, if indicated, at time of hospitalisation.

Interpretation: This Europe-wide consensus document is the first attempt to standardise the assessment and care of patients hospitalised for COPD exacerbations. This should be regarded as the starting point to build knowledge and evidence on patients hospitalised for COPD exacerbations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/COPD.S287705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896731PMC
February 2021

Beta-blocker therapy in patients with COPD: a systematic literature review and meta-analysis with multiple treatment comparison.

Respir Res 2021 Feb 23;22(1):64. Epub 2021 Feb 23.

National Heart and Lung Institute, Imperial College London, Manresa Road, London, UK.

Background: Beta-blockers are associated with reduced mortality in patients with cardiovascular disease but are often under prescribed in those with concomitant COPD, due to concerns regarding respiratory side-effects. We investigated the effects of beta-blockers on outcomes in patients with COPD and explored within-class differences between different agents.

Methods: We searched the Cochrane Central Register of Controlled Trials, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Medline for observational studies and randomized controlled trials (RCTs) investigating the effects of beta-blocker exposure versus no exposure or placebo, in patients with COPD, with and without cardiovascular indications. A meta-analysis was performed to assess the association of beta-blocker therapy with acute exacerbations of COPD (AECOPD), and a network meta-analysis was conducted to investigate the effects of individual beta-blockers on FEV1. Mortality, all-cause hospitalization, and quality of life outcomes were narratively synthesized.

Results: We included 23 observational studies and 14 RCTs. In pooled observational data, beta-blocker therapy was associated with an overall reduced risk of AECOPD versus no therapy (HR 0.77, 95%CI 0.70 to 0.85). Among individual beta-blockers, only propranolol was associated with a relative reduction in FEV1 versus placebo, among 199 patients evaluated in RCTs. Narrative syntheses on mortality, all-cause hospitalization and quality of life outcomes indicated a high degree of heterogeneity in study design and patient characteristics but suggested no detrimental effects of beta-blocker therapy on these outcomes.

Conclusion: The class effect of beta-blockers remains generally positive in patients with COPD. Reduced rates of AECOPD, mortality, and improved quality of life were identified in observational studies, while propranolol was the only agent associated with a deterioration of lung function in RCTs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12931-021-01661-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903749PMC
February 2021

A semi-supervised approach for rapidly creating clinical biomarker phenotypes in the UK Biobank using different primary care EHR and clinical terminology systems.

JAMIA Open 2020 Dec 5;3(4):545-556. Epub 2020 Dec 5.

Institute of Health Informatics, University College London, London, UK.

Objectives: The UK Biobank (UKB) is making primary care electronic health records (EHRs) for 500 000 participants available for COVID-19-related research. Data are extracted from four sources, recorded using five clinical terminologies and stored in different schemas. The aims of our research were to: (a) develop a semi-supervised approach for bootstrapping EHR phenotyping algorithms in UKB EHR, and (b) to evaluate our approach by implementing and evaluating phenotypes for 31 common biomarkers.

Materials And Methods: We describe an algorithmic approach to phenotyping biomarkers in primary care EHR involving (a) bootstrapping definitions using existing phenotypes, (b) excluding generic, rare, or semantically distant terms, (c) forward-mapping terminology terms, (d) expert review, and (e) data extraction. We evaluated the phenotypes by assessing the ability to reproduce known epidemiological associations with all-cause mortality using Cox proportional hazards models.

Results: We created and evaluated phenotyping algorithms for 31 biomarkers many of which are directly related to COVID-19 complications, for example diabetes, cardiovascular disease, respiratory disease. Our algorithm identified 1651 Read v2 and Clinical Terms Version 3 terms and automatically excluded 1228 terms. Clinical review excluded 103 terms and included 44 terms, resulting in 364 terms for data extraction (sensitivity 0.89, specificity 0.92). We extracted 38 190 682 events and identified 220 978 participants with at least one biomarker measured.

Discussion And Conclusion: Bootstrapping phenotyping algorithms from similar EHR can potentially address pre-existing methodological concerns that undermine the outputs of biomarker discovery pipelines and provide research-quality phenotyping algorithms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jamiaopen/ooaa047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717266PMC
December 2020

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

Lancet Digit Health 2021 04 18;3(4):e217-e230. Epub 2021 Feb 18.

Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK; Health Data Research UK, London, UK.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2589-7500(21)00017-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985613PMC
April 2021

Increased mortality risk in patients with primary and secondary adrenal insufficiency.

J Clin Endocrinol Metab 2021 Feb 17. Epub 2021 Feb 17.

Department of Metabolic Medicine, St. Mary's Hospital, Imperial College NHS trust, London, UK.

Context: Mortality data in patients with adrenal insufficiency are inconsistent, possibly due to temporal and geographical differences between patients and their reference populations.

Objective: To compare mortality risk and causes of death in adrenal insufficiency with an individually-matched reference population.

Design: Retrospective cohort study.

Setting: UK general practitioner database (CPRD).

Participants: 6821 patients with adrenal insufficiency (primary, 2052; secondary, 3948) and 67564 individually-matched controls (primary, 20366; secondary, 39134).

Main Outcome Measures: All-cause and cause-specific mortality; hospital admission from adrenal crisis.

Results: With follow-up of 40799 and 406899 person-years for patients and controls respectively, the hazard ratio (HR; [95%CI]) for all-cause mortality was 1.68 [1.58 - 1.77]. HRs were greater in primary (1.83 [1.66 - 2.02]) than in secondary (1.52 [1.40 - 1.64]) disease; (HR; primary versus secondary disease, 1.16 [1.03 - 1.30]). The leading cause of death was cardiovascular disease (HR 1.54 [1.32-1.80]), along with malignant neoplasms and respiratory disease. Deaths from infection were also relatively high (HR 4.00 [2.15 - 7.46]). Adrenal crisis contributed to 10% of all deaths. In the first two years following diagnosis, the patients' mortality rate and hospitalisation from adrenal crisis were higher than in later years.

Conclusion: Mortality was increased in adrenal insufficiency, especially primary, even with individual matching and was observed early in the disease course. Cardiovascular disease was the major cause but mortality from infection was also high. Adrenal crisis was a common contributor. Early education for prompt treatment of infections and avoidance of adrenal crisis hold potential to reduce mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgab096DOI Listing
February 2021

Cardiovascular disease in patients with primary and secondary adrenal insufficiency and the role of comorbidities.

J Clin Endocrinol Metab 2021 Feb 15. Epub 2021 Feb 15.

Department of Metabolic Medicine, St. Mary's Hospital, Imperial College NHS trust, London, UK.

Context: Mortality studies have established that cardiovascular disease is the leading cause of death in patients with adrenal insufficiency and the risk is greater than that observed in individually-matched controls.

Objective: Here we have performed a detailed analysis of cardiovascular morbidity and mortality, taking account of the role of co-morbidities.

Design: Retrospective cohort study.

Setting: UK general practitioner database (CPRD).

Participants: 6821 patients with adrenal insufficiency (primary, 2052; secondary, 3948) compared with 67564 individually-matched controls, with and without adjustment for comorbidities (diabetes, hypertension, dyslipidaemia, previous cardiovascular disease, and smoking).

Main Outcome Measures: Composite cardiovascular events recorded in CPRD and cardiovascular mortality in those participants with linked national mortality data.

Results: Hazard ratios (95%CI) for composite cardiovascular events in patients with adrenal insufficiency of any cause were 1.28 (1.20-1.36, unadjusted) and 1.07 (1.01-1.14, adjusted). Increased cerebrovascular events in patients with secondary adrenal insufficiency accounted for most of the increased hazard (1.53 (1.34-1.74, adjusted)) and were associated with cranial irradiation therapy. Cardiovascular mortality data were available for 3547 patients and 34944 controls. The adjusted hazard ratio for ischaemic heart disease mortality was 1.86 (1.25-2.78) for primary adrenal insufficiency and 1.39 (1.02-1.89) for secondary.

Conclusion: Co-morbidities largely accounted for the increased cardiovascular events but in secondary adrenal insufficiency, cerebrovascular events were independently increased and associated with irradiation treatment. However, the risk of cardiovascular mortality remained increased even following adjustment for co-morbidities in both primary and secondary adrenal insufficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgab063DOI Listing
February 2021

Predictors of pulmonary rehabilitation completion in the UK.

ERJ Open Res 2021 Jan 8;7(1). Epub 2021 Feb 8.

NIHR Leicester Respiratory Biomedical Research Centre, Dept of Respiratory Sciences, University of Leicester, Leicester, UK.

Introduction: Pulmonary rehabilitation has been shown to improve dyspnoea, fatigue, quality of life and exercise capacity in individuals with chronic obstructive pulmonary disease (COPD). Our aim was to determine the characteristics of people with COPD associated with completion of pulmonary rehabilitation.

Methods: This was a cross-sectional analysis of 7060 people with COPD enrolled in pulmonary rehabilitation between January 1, 2017 and March 31, 2017. Data were from a UK national audit of COPD care. Factors associated with pulmonary rehabilitation completion were determined using mixed effects logistic regression with a random intercept for pulmonary rehabilitation service. Factors chosen for assessment based on clinical judgement and data availability were age, sex, country, socioeconomic status, body mass index, referral location, programme type, start within 90 days, smoking status, oxygen therapy, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage, Medical Research Council (MRC) dyspnoea grade, any exercise test and any health status questionnaire.

Results: 4635 (66%) people with COPD completed a pulmonary rehabilitation programme. People that were aged ≥60 years, resident in Wales, referred within 90 days, an ex- or never-smoker, received an exercise test, or received a health status questionnaire had significantly greater odds of completing pulmonary rehabilitation. People that were in the most deprived quintile, underweight or very severely obese, enrolled in a rolling rather than a cohort programme, had a higher GOLD stage and had a higher MRC grade had significantly lower odds of completing pulmonary rehabilitation.

Conclusions: People with COPD were more likely to complete pulmonary rehabilitation when best practice guidelines were followed. People with more severe COPD symptoms and those enrolled in rolling rather than cohort programmes were less likely to complete pulmonary rehabilitation. Referring people with COPD in the earlier stages of disease, ensuring programmes follow best practice guidelines and favouring cohort over rolling programmes could improve rates of pulmonary rehabilitation completion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/23120541.00509-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869604PMC
January 2021

Personal exposure to air pollution and respiratory health of COPD patients in London.

Eur Respir J 2021 Feb 4. Epub 2021 Feb 4.

Environmental Research Group, MRC Centre for Environment and Health, Imperial College London, London, UK.

Previous studies have investigated the effects of air pollution on chronic obstructive pulmonary disease (COPD) patients using either fixed site measurements or a limited number of personal measurements, usually for one pollutant and a short time period. These limitations may introduce bias and distort the epidemiological associations as they do not account for all the potential sources or the temporal variability of pollution.We used detailed information on individuals' exposure to various pollutants measured at fine spatio-temporal scale to obtain more reliable effect estimates. A panel of 115 patients was followed up for an average continuous period of 128 days carrying a personal monitor specifically designed for this project that measured temperature, PM, PM, NO, NO, CO and O at one-minute time resolution. Each patient recorded daily information on respiratory symptoms and measured peak expiratory flow (PEF). A pulmonologist combined related data to define a binary variable denoting an "exacerbation". The exposure-response associations were assessed with mixed-effects models.We found that gaseous pollutants were associated with a deterioration in patients' health. We observed an increase of 16.4% (95% confidence interval: 8.6-24.6%), 9.4% (5.4-13.6%) and 7.6% (3.0-12.4%) in the odds of exacerbation for an interquartile range increase in NO, NO and CO respectively. Similar results were obtained for cough and sputum. O was found to have adverse associations with PEF and breathlessness. No association was observed between particles and any outcome.Our findings suggest that, when considering total personal exposure to air pollutants, mainly the gaseous pollutants affect COPD patients' health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/13993003.03432-2020DOI Listing
February 2021

Health impact assessment to predict the impact of tobacco price increases on COPD burden in Italy, England and Sweden.

Sci Rep 2021 Jan 27;11(1):2311. Epub 2021 Jan 27.

National Heart and Lung Institute, Emmanuel Kaye Building, Imperial College London, 1B Manresa Road, London, SW3 6LR, UK.

Raising tobacco prices effectively reduces smoking, the main risk factor for chronic obstructive pulmonary disease (COPD). Using the Health Impact Assessment tool "DYNAMO-HIA", this study quantified the reduction in COPD burden that would occur in Italy, England and Sweden over 40 years if tobacco prices were increased by 5%, 10% and 20% over current local prices, with larger increases considered in secondary analyses. A dynamic Markov-based multi-state simulation modelling approach estimated the effect of changes in smoking prevalence states and probabilities of transitioning between smoking states on future smoking prevalence, COPD burden and life expectancy in each country. Data inputs included demographics, smoking prevalences and behaviour and COPD burden from national data resources, large observational cohorts and datasets within DYNAMO-HIA. In the 20% price increase scenario, the cumulative number of COPD incident cases saved over 40 years was 479,059 and 479,302 in Italy and England (populous countries with higher smoking prevalences) and 83,694 in Sweden (smaller country with lower smoking prevalence). Gains in overall life expectancy ranged from 0.25 to 0.45 years for a 20 year-old. Increasing tobacco prices would reduce COPD burden and increase life expectancy through smoking behavior changes, with modest but important public health benefits observed in all three countries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-81876-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840977PMC
January 2021

Withdrawal of inhaled corticosteroids versus continuation of triple therapy in patients with COPD in real life: observational comparative effectiveness study.

Respir Res 2021 Jan 21;22(1):25. Epub 2021 Jan 21.

Pneumology Department, Hospital Universitari Vall D'Hebron, Vall D'Hebron Institut de Recerca (VHIR), CIBER de Enfermedades Respiratorias (CIBERES), Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.

Background: Inhaled corticosteroids (ICS) are indicated for prevention of exacerbations in patients with COPD, but they are frequently overprescribed. ICS withdrawal has been recommended by international guidelines in order to prevent side effects in patients in whom ICS are not indicated.

Method: Observational comparative effectiveness study aimed to evaluate the effect of ICS withdrawal versus continuation of triple therapy (TT) in COPD patients in primary care. Data were obtained from the Optimum Patient Care Research Database (OPCRD) in the UK.

Results: A total of 1046 patients who withdrew ICS were matched 1:4 by time on TT to 4184 patients who continued with TT. Up to 76.1% of the total population had 0 or 1 exacerbation the previous year. After controlling for confounders, patients who discontinued ICS did not have an increased risk of moderate or severe exacerbations (adjusted HR: 1.04, 95% confidence interval (CI) 0.94-1.15; p = 0.441). However, rates of exacerbations managed in primary care (incidence rate ratio (IRR) 1.33, 95% CI 1.10-1.60; p = 0.003) or in hospital (IRR 1.72, 95% CI 1.03-2.86; p = 0.036) were higher in the cessation group. Unsuccessful ICS withdrawal was significantly and independently associated with more frequent courses of oral corticosteroids the previous year and with a blood eosinophil count ≥ 300 cells/μL.

Conclusions: In this primary care population of patients with COPD, composed mostly of infrequent exacerbators, discontinuation of ICS from TT was not associated with an increased risk of exacerbation; however, the subgroup of patients with more frequent courses of oral corticosteroids and high blood eosinophil counts should not be withdrawn from ICS. Trial registration European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (EUPAS30851).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12931-021-01615-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818945PMC
January 2021

Model-based comorbidity clusters in patients with heart failure: association with clinical outcomes and healthcare utilization.

BMC Med 2021 Jan 18;19(1). Epub 2021 Jan 18.

Department of Population Health, National Heart and Lung Institute, Imperial College London, London, UK.

Background: Comorbidities affect outcomes in heart failure (HF), but are not reflected in current HF classification. The aim of this study is to characterize HF groups that account for higher-order interactions between comorbidities and to investigate the association between comorbidity groups and outcomes.

Methods: Latent class analysis (LCA) was performed on 12 comorbidities from patients with HF identified from administrative claims data in the USA (OptumLabs Data Warehouse®) between 2008 and 2018. Associations with admission to hospital and mortality were assessed with Cox regression. Negative binomial regression was used to examine rates of healthcare use.

Results: In a population of 318,384 individuals, we identified five comorbidity clusters, named according to their dominant features: low-burden, metabolic-vascular, anemic, ischemic, and metabolic. Compared to the low-burden group (minimal comorbidities), patients in the metabolic-vascular group (exhibiting a pattern of diabetes, obesity, and vascular disease) had the worst prognosis for admission (HR 2.21, 95% CI 2.17-2.25) and death (HR 1.87, 95% CI 1.74-2.01), followed by the ischemic, anemic, and metabolic groups. The anemic group experienced an intermediate risk of admission (HR 1.49, 95% CI 1.44-1.54) and death (HR 1.46, 95% CI 1.30-1.64). Healthcare use also varied: the anemic group had the highest rate of outpatient visits, compared to the low-burden group (IRR 2.11, 95% CI 2.06-2.16); the metabolic-vascular and ischemic groups had the highest rate of admissions (IRR 2.11, 95% CI 2.08-2.15, and 2.11, 95% CI 2.07-2.15) and healthcare costs.

Conclusions: These data demonstrate the feasibility of using LCA to classify HF based on comorbidities alone and should encourage investigation of multidimensional approaches in comorbidity management to reduce admission and mortality risk among patients with HF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12916-020-01881-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812726PMC
January 2021

Burden of preschool wheeze and progression to asthma in the UK: Population-based cohort 2007 to 2017.

J Allergy Clin Immunol 2021 Jan 13. Epub 2021 Jan 13.

National Heart and Lung Institute, Imperial College London, London, United Kingdom.

Background: Wheeze is one of the most common symptoms of preschool children (age 1-5 years), yet we have little understanding of the burden in the United Kingdom.

Objectives: We sought to determine prevalence and pattern of physician-confirmed preschool wheeze, related health care utilization, and factors associated with progression to school-age asthma.

Methods: We used nationally representative primary and secondary care electronic medical records between 2007 and 2017 to identify preschool children with wheeze. Factors associated with asthma progression were identified in a nested cohort of children with follow-up from age 1 to 2 years, until at least age 8 years.

Results: From 1,021,624 preschool children, 69,261 were identified with wheeze. Prevalence of preschool wheeze was 7.7% in 2017. Wheeze events were lowest in August and highest in late-autumn/early-winter. During median follow-up of 2 years (interquartile range, 1.2-4.0 years), 15.8% attended an emergency department, and 13.9% had a hospital admission, for a respiratory disorder. The nested cohort with prolonged follow-up identified 15,085 children; 35.5% progressed to asthma between age 5 and 8 years. Of children with preschool wheeze, without an asthma diagnosis, 34.9% were prescribed inhaled corticosteroids and 15.6% oral corticosteroids. The factors most strongly associated with progression to asthma were wheeze frequency and severity, atopy, prematurity, maternal asthma severity, and first reported wheeze event occurring in September.

Conclusions: Preschool wheeze causes considerable health care burden, and a large number of children are prescribed asthma medication and have unplanned secondary care visits. Multiple factors influence progression to asthma, including first wheeze event occurring in September.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2020.12.643DOI Listing
January 2021

Current smoking and COVID-19 risk: results from a population symptom app in over 2.4 million people.

Thorax 2021 Jan 5. Epub 2021 Jan 5.

The Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.

Background: The association between current tobacco smoking, the risk of developing symptomatic COVID-19 and the severity of illness is an important information gap.

Methods: UK users of the Zoe COVID-19 Symptom Study app provided baseline data including demographics, anthropometrics, smoking status and medical conditions, and were asked to log their condition daily. Participants who reported that they did not feel physically normal were then asked by the app to complete a series of questions, including 14 potential COVID-19 symptoms and about hospital attendance. The main study outcome was the development of 'classic' symptoms of COVID-19 during the pandemic defined as fever, new persistent cough and breathlessness and their association with current smoking. The number of concurrent COVID-19 symptoms was used as a proxy for severity and the pattern of association between symptoms was also compared between smokers and non-smokers.

Results: Between 24 March 2020 and 23 April 2020, data were available on 2 401 982 participants, mean (SD) age 43.6 (15.1) years, 63.3% female, overall smoking prevalence 11.0%. 834 437 (35%) participants reported being unwell and entered one or more symptoms. Current smokers were more likely to report symptoms suggesting a diagnosis of COVID-19; classic symptoms adjusted OR (95% CI) 1.14 (1.10 to 1.18); >5 symptoms 1.29 (1.26 to 1.31); >10 symptoms 1.50 (1.42 to 1.58). The pattern of association between reported symptoms did not vary between smokers and non-smokers.

Interpretation: These data are consistent with people who smoke being at an increased risk of developing symptomatic COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/thoraxjnl-2020-216422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789201PMC
January 2021

Feasibility of using Clinical Practice Research Datalink data to identify patients with chronic obstructive pulmonary disease to enrol into real-world trials.

Pharmacoepidemiol Drug Saf 2021 Apr 9;30(4):472-481. Epub 2021 Jan 9.

Respiratory Epidemiology, GlaxoSmithKline, Brentford, UK.

Purpose: To assess the feasibility of using Clinical Practice Research Datalink (CPRD) data for identifying populations of patients with chronic obstructive pulmonary disease (COPD) eligible for a hypothetical pragmatic trial.

Methods: A retrospective multidatabase cohort study using CPRD primary care and linked secondary care data to describe the characteristics of populations of patients with COPD. Patients' demographic and lifestyle factors, comorbidity profile, spirometry measurements and treatment changes were evaluated, as was the distribution of follow-up time and types of losses during follow-up. Characteristics were evaluated using descriptive statistics.

Results: A total of 322 991 patients from 1148 primary care practices in the United Kingdom across two CPRD primary care databases, CPRD GOLD and CPRD Aurum, were potentially eligible to participate in a hypothetical trial using CPRD, starting on 31 December 2017. Patients with COPD in CPRD GOLD and CPRD Aurum were comparable in terms of age (median age 70 vs. 68 years), gender (50% vs. 52% male), disease severity (e.g., 25% vs. 24% Medical Research Council [MRC] dyspnoea score grades 3-5) and history of respiratory conditions (e.g., 43% vs. 38% asthma). High proportions of patients with COPD in CPRD GOLD and CPRD Aurum were available on 31 December 2012 for follow-up at 1, 2, and 5 years (92%, 85% and 67%, respectively).

Conclusions: Patients and data from CPRD GOLD and CPRD Aurum were comparable across key aspects relevant to COPD trials. A pragmatic trial using CPRD to recruit patients with COPD is scientifically feasible.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pds.5188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986187PMC
April 2021

Prescribing Pathways to Triple Therapy: A Retrospective Observational Study of Adults with Chronic Obstructive Pulmonary Disease in the UK.

Int J Chron Obstruct Pulmon Dis 2020 8;15:3261-3271. Epub 2020 Dec 8.

Real World Science and Digital, BioPharmaceuticals Medical, AstraZeneca, Gothenburg, Sweden.

Purpose: Treatment guidance for chronic obstructive pulmonary disease (COPD) recommends inhaled corticosteroid (ICS)+long-acting muscarinic antagonist+long-acting β-agonist (LABA) triple therapy for patients who experience recurrent exacerbations, persistent breathlessness, or exercise limitation on dual therapy. However, information is limited on pathways to triple therapy in the UK.

Patients And Methods: A retrospective cohort study was conducted using de-identified patient-level data from UK primary care electronic medical records from January 1, 2005 to May 1, 2016. Data were included from patients who had their first triple therapy regimen (index date) recorded during the study period and a minimum of 12 months' pre-index data. Treatment pathways to triple therapy were recorded, and the proportion of patients on triple therapy before their COPD diagnosis was determined. Adherence to triple therapy was estimated using the proportion of days covered (PDC).

Results: After applying eligibility criteria, 82,300 patients were included, with a mean age at COPD diagnosis of 64.7 years. The major treatment pathway (27.9%) was the first initiation of ICS+LABA prior to triple therapy. Following COPD diagnosis, the median time to triple therapy was approximately 3.5 years. The estimated mean adherence to triple therapy was 81.8% PDC. Multivariate analysis showed that the following groups were more likely to have received previous therapy prior to triple therapy: females (versus males), patients with asthma (versus those without asthma), severe COPD (versus those with non-severe COPD), or fewer exacerbations (versus those with more exacerbations).

Conclusion: Treatment pathways to triple therapy in the UK are diverse, highlighting the need to better understand factors involved in clinical decision-making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/COPD.S278101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733404PMC
December 2020

Belief of having had unconfirmed Covid-19 infection reduces willingness to participate in app-based contact tracing.

NPJ Digit Med 2020 Nov 6;3(1):146. Epub 2020 Nov 6.

National Heart and Lung Institute, Imperial College London, London, UK.

Contact tracing and lockdown are health policies being used worldwide to combat the coronavirus (COVID-19). The UK National Health Service (NHS) Track and Trace Service has plans for a nationwide app that notifies the need for self-isolation to those in contact with a person testing positive for COVID-19. To be successful, such an app will require high uptake, the determinants and willingness for which are unclear but essential to understand for effective public health benefit. The objective of this study was to measure the determinants of willingness to participate in an NHS app-based contact-tracing programme using a questionnaire within the Care Information Exchange (CIE)-the largest patient-facing electronic health record in the NHS. Among 47,708 registered NHS users of the CIE, 27% completed a questionnaire asking about willingness to participate in app-based contact tracing, understanding of government advice, mental and physical wellbeing and their healthcare utilisation-related or not to COVID-19. Descriptive statistics are reported alongside univariate and multivariable logistic regression models, with positive or negative responses to a question on app-based contact tracing as the dependent variable. 26.1% of all CIE participants were included in the analysis (N = 12,434, 43.0% male, mean age 55.2). 60.3% of respondents were willing to participate in app-based contact tracing. Out of those who responded 'no', 67.2% stated that this was due to privacy concerns. In univariate analysis, worsening mood, fear and anxiety in relation to changes in government rules around lockdown were associated with lower willingness to participate. Multivariable analysis showed that difficulty understanding government rules was associated with a decreased inclination to download the app, with those scoring 1-2 and 3-4 in their understanding of the new government rules being 45% and 27% less inclined to download the contact-tracing app, respectively; when compared to those who rated their understanding as 5-6/10 (OR for 1-2/10 = 0.57 [CI 0.48-0.67]; OR for 3-4/10 = 0.744 [CI 0.64-0.87]), whereas scores of 7-8 and 9-10 showed a 43% and 31% respective increase. Those reporting an unconfirmed belief of having previously had and recovered from COVID-19 were 27% less likely to be willing to download the app; belief of previous recovery from COVID-19 infection OR 0.727 [0.585-0.908]). In this large UK-wide questionnaire of wellbeing in lockdown, a willingness for app-based contact tracing over an appropriate age range is 60%-close to the estimated 56% population uptake, and substantially less than the smartphone-user uptake considered necessary for an app-based contact tracing to be an effective intervention to help suppress an epidemic. Difficulty comprehending government advice and uncertainty of diagnosis, based on a public health policy of not testing to confirm self-reported COVID-19 infection during lockdown, therefore reduce willingness to adopt a government contact-tracing app to a level below the threshold for effectiveness as a tool to suppress an epidemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41746-020-00357-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648058PMC
November 2020

The Role of Individual and Neighborhood Factors on Racial Disparity in Respiratory Outcomes: Won't You Be My Neighbor?

Am J Respir Crit Care Med 2020 Dec 9. Epub 2020 Dec 9.

Imperial College London, 4615, Department of Primary Care and Public Health, London, United Kingdom of Great Britain and Northern Ireland.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.202010-3875EDDOI Listing
December 2020

Development and Validation of a Method to Estimate COPD Severity in Multiple Datasets: A Retrospective Study.

Pulm Ther 2020 Dec 7. Epub 2020 Dec 7.

Real World Science and Digital, BioPharmaceuticals Medical, AstraZeneca, Gothenburg, Sweden.

Introduction: Outcomes in chronic obstructive pulmonary disease (COPD) such as symptoms, hospitalisations and mortality rise with increasing disease severity. However, the heterogeneity of electronic medical records presents a significant challenge in measuring severity across geographies. We aimed to develop and validate a method to approximate COPD severity using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 classification scheme, which categorises patients based on forced expiratory volume in 1 s, hospitalisations and the modified Medical Research Council dyspnoea scale or COPD Assessment Test.

Methods: This analysis was part of a comprehensive retrospective study, including patients sourced from the IQVIA Medical Research Data [IMRD; incorporating data from The Health Improvement Network (THIN), a Cegedim database] and the Clinical Practice Research Datalink (CPRD) in the UK, the Disease Analyzer in Germany and the Longitudinal Patient Data in Italy, France and Australia. Patients in the CPRD with the complete set of information required to calculate GOLD 2011 groups were used to develop the method. Ordinal logistic models at COPD diagnosis and at index (first episode of triple therapy) were then used to validate the method to estimate COPD severity, and this was applied to the full study population to estimate GOLD 2011 categories.

Results: Overall, 4579 and 12,539 patients were included in the model at COPD diagnosis and at index, respectively. Models correctly classified 74.4% and 75.9% of patients into severe and non-severe categories at COPD diagnosis and at index, respectively. Age, gender, time between diagnosis and start of triple therapy, healthcare resource use, comorbid conditions and prescriptions were included as covariates.

Conclusion: This study developed and validated a method to approximate disease severity based on GOLD 2011 categories that can potentially be used in patients without all the key parameters needed for this calculation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s41030-020-00139-0DOI Listing
December 2020

Characteristics Associated with Accelerated Lung Function Decline in a Primary Care Population with Chronic Obstructive Pulmonary Disease.

Int J Chron Obstruct Pulmon Dis 2020 25;15:3079-3091. Epub 2020 Nov 25.

Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College London, London, UK.

Background: Estimates for lung function decline in chronic obstructive pulmonary disease (COPD) have differed by study setting and have not been described in a UK primary care population.

Purpose: To describe rates of FEV and FVC decline in COPD and investigate characteristics associated with accelerated decline.

Patients And Methods: Current/ex-smoking COPD patients (35 years+) who had at least 2 FEV or FVC measurements ≥6 months apart were included using Clinical Practice Research Datalink. Patients were followed up for a maximum of 13 years. Accelerated rate of lung function decline was defined as the fastest quartile of decline using mixed linear regression, and association with baseline characteristics was investigated using logistic regression.

Results: A total of 72,683 and 50,649 COPD patients had at least 2 FEV or FVC measurements, respectively. Median rates of FEV and FVC changes or decline were -18.1mL/year (IQR: -31.6 to -6.0) and -22.7mL/year (IQR: -39.9 to -6.7), respectively. Older age, high socioeconomic status, being underweight, high mMRC dyspnoea and frequent AECOPD or severe AECOPD were associated with an accelerated rate of FEV and FVC decline. Current smoking, mild airflow obstruction and inhaled corticosteroid treatment were additionally associated with accelerated FEV decline whilst women, sputum production and severe airflow obstruction were associated with accelerated FVC decline.

Conclusion: Rate of FEV and FVC decline was similar and showed similar heterogeneity. Whilst FEV and FVC shared associations with baseline characteristics, a few differences highlighted the importance of both lung function measures in COPD progression. We identified important characteristics that should be monitored for disease progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/COPD.S278981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701160PMC
November 2020

Lung volume reduction eligibility in patients with COPD completing pulmonary rehabilitation: results from the UK National Asthma and COPD Audit Programme.

BMJ Open 2020 11 27;10(11):e040942. Epub 2020 Nov 27.

National Heart and Lung Insititute, Imperial College London, London, UK

Objectives: To establish what proportion of patients completing a UK pulmonary rehabilitation (PR) programme meet the 2018 National Institute for Health and Care Excellence (NICE) chronic obstructive pulmonary disease (COPD) guideline (NG115) criteria to have a respiratory review to establish whether referral to a lung volume reduction multidisciplinary team would be appropriate. This respiratory review would include evaluation of the presence of hyperinflation and the presence of emphysema on CT scan. The NICE criteria include measures of breathlessness and exercise capacity but these parameters are not completely defined.

Design: Observational study.

Setting: PR programmes across the UK in 2015 (210 centres) and 2017 (184 centres) entering data into the Royal College of Physicians' National Asthma and COPD Audit Programme.

Participants: 8295 (55.7%) of 14 889 patients in programmes using incremental shuttle walk test (ISWT) or 6-minute walk test (6MWT) as an outcome measure completed PR, and 4856 (32.6%) had complete data recorded (6MWT/ISWT, baseline spirometry, Medical Research Council (MRC) dyspnoea score).

Results: Depending on the walking test safety threshold adopted for the ISWT (≥140 m or ≥ 80 m) and the MRC dyspnoea score threshold used (MRC score ≥3 or ≥4 at the end of PR), between 4.9% and 18.1% of PR completers met the NICE criteria for a lung volume reduction-focused respiratory review.

Conclusions: Lung volume reduction therapies are beneficial in appropriately selected patients with COPD, but few procedures are performed, and treatment pathways are unclear. These data help to inform the feasibility of the approach recommended by NICE and highlight the need for future systematic pathways to reduce inequalities in patients being considered for effective treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-040942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703433PMC
November 2020

Predictors of Referral to Pulmonary Rehabilitation from UK Primary Care.

Int J Chron Obstruct Pulmon Dis 2020 16;15:2941-2952. Epub 2020 Nov 16.

NIHR Leicester Respiratory Biomedical Research Centre, Department of Respiratory Sciences, University of Leicester, Leicester, UK.

Background: A large proportion of people with COPD are not referred to pulmonary rehabilitation (PR) despite its proven benefits. No previous studies have examined predictors of referral to PR.

Objective: To determine the characteristics of people with COPD associated with referral to PR.

Methods: Cross-sectional analysis of a primary care cohort of 82,696 Welsh people with COPD generated as part of a UK national audit of COPD care. Data represent care received by patients as of 31/03/2017. Referral to PR was defined as any code in the patient record indicating referral to PR in the last 3 years. Potential predictors of referral to PR were chosen based on clinical judgement and data availability. Independent predictors of PR referral were determined using backward stepwise mixed-effects logistic regression with a random effect for practice. Variables assessed were: age, gender, deprivation, MRC recorded in past year, MRC grade, smoking status recorded in past year, smoking status, number of exacerbations in past year, inhaled therapy prescription, influenza vaccination, and comorbidities of diabetes, hypertension, coronary heart disease, stroke, heart failure, lung cancer, asthma, bronchiectasis, depression, anxiety, severe mental illness, osteoporosis, and painful condition.

Results: A total of 13,297 people (16%) with COPD were referred from primary care for PR. Patients with a comorbidity of bronchiectasis or depression, MRC recorded in the last year, higher MRC grade, more exacerbations in the last year, a greater level of inhaled therapy, an influenza vaccination, or were an ex-smoker had significantly higher odds of referral to PR. Patients that were older, female, more deprived, or had a comorbidity of diabetes, asthma, or painful condition had significantly lower odds of referral to PR.

Conclusion: Generally appropriate patients are being prioritised for PR referral; however, it is concerning that women, current smokers, and more deprived patients appear to have lower odds of referral.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/COPD.S273336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678715PMC
November 2020

Real world effects of COPD medications: a cohort study with validation against results from randomised controlled trials.

Eur Respir J 2021 Mar 25;57(3). Epub 2021 Mar 25.

Dept of Non-communicable Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.

Real-world data provide the potential for generating evidence on drug treatment effects in groups excluded from trials, but rigorous, validated methodology for doing so is lacking. We investigated whether non-interventional methods applied to real-world data could reproduce results from the landmark TORCH COPD trial.We performed a historical cohort study (2000-2017) of COPD drug treatment effects in the UK Clinical Practice Research Datalink (CPRD). Two control groups were selected from CPRD by applying TORCH inclusion/exclusion criteria and 1:1 matching to TORCH participants, as follows. Control group 1: people with COPD not prescribed fluticasone propionate (FP)-salmeterol (SAL); control group 2: people with COPD prescribed SAL only. FP-SAL exposed groups were then selected from CPRD by propensity score matching to each control group. Outcomes studied were COPD exacerbations, death from any cause and pneumonia.2652 FP-SAL exposed people were propensity score matched to 2652 FP-SAL unexposed people while 991 FP-SAL exposed people were propensity score matched to 991 SAL exposed people. Exacerbation rate ratio was comparable to TORCH for FP-SAL SAL (0.85, 95% CI 0.74-0.97 0.88, 0.81-0.95) but not for FP-SAL no FP-SAL (1.30, 1.19-1.42 0.75, 0.69-0.81). In addition, active comparator results were consistent with TORCH for mortality (hazard ratio 0.93, 0.65-1.32 0.93, 0.77-1.13) and pneumonia (risk ratio 1.39, 1.04-1.87 1.47, 1.25-1.73).We obtained very similar results to the TORCH trial for active comparator analyses, but were unable to reproduce placebo-controlled results. Application of these validated methods for active comparator analyses to groups excluded from randomised controlled trials provides a practical way for contributing to the evidence base and supporting COPD treatment decisions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/13993003.01586-2020DOI Listing
March 2021

Prescribing Pathways to Triple Therapy: A Multi-Country, Retrospective Observational Study of Adult Patients with Chronic Obstructive Pulmonary Disease.

Pulm Ther 2020 Dec 16;6(2):333-350. Epub 2020 Oct 16.

BioPharmaceuticals Medical, Real World Science and Digital, AstraZeneca, Gothenburg, Sweden.

Introduction: Maintenance treatment strategies in COPD recommend inhaled corticosteroid (ICS) + long-acting muscarinic antagonist (LAMA) + long-acting β-agonist (LABA) triple therapy after initial dual therapy. Little is known about how treatment pathways to triple therapy vary across countries in clinical practice.

Methods: This multi-country, retrospective cohort study (conducted 1 January 2005-1 May 2016) included patients with a COPD diagnosis, and (UK only) evidence of smoking history, or (France, Italy, Germany, and Australia) an indicator confirming COPD diagnosis, a first instance of triple therapy recorded during the study period and ≥ 12 months of data prior to this date. Treatment pathways to triple therapy were analyzed in patients whose first instance of triple therapy was on or after the initial COPD diagnosis. The proportion of patients who initiated triple therapy prior to initial COPD diagnosis was also estimated. Meta-analyses of the main results were performed.

Results: In 130,729 patients across all countries, mean age (standard deviation) ranged from 63.4 (10.4) years (Germany) to 69.8 (9.9) years (Italy), and median time (interquartile range) from initial COPD diagnosis to first prescription of triple therapy ranged from 16.9 (5.7-36.2) months (Australia) to 42.5 (13.9-87.4) months (UK). ICS + LABA was the most common treatment pathway prior to triple therapy in the UK, Germany, and Italy (27.3%-31.6%); no previous maintenance therapy prior to triple therapy was the most common pathway in France and Australia (32.5% and 37.9%, respectively). Meta-analyses provided a pooled estimate of 20.4% (95% confidence interval: 13.8%-29.1%) for the proportion of patients initiating triple therapy at or before initial COPD diagnosis.

Conclusions: In this retrospective cohort study, treatment pathways to triple therapy were diverse within and between countries. The differing impact of treatments may affect quality of life and disease control in patients with COPD. Further analyses should investigate factors influencing pathways to triple therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s41030-020-00132-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672143PMC
December 2020

Outcome of Hospitalization for COVID-19 in Patients with Interstitial Lung Disease. An International Multicenter Study.

Am J Respir Crit Care Med 2020 12;202(12):1656-1665

Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom.

The impact of coronavirus disease (COVID-19) on patients with interstitial lung disease (ILD) has not been established. To assess outcomes in patients with ILD hospitalized for COVID-19 versus those without ILD in a contemporaneous age-, sex-, and comorbidity-matched population. An international multicenter audit of patients with a prior diagnosis of ILD admitted to the hospital with COVID-19 between March 1 and May 1, 2020, was undertaken and compared with patients without ILD, obtained from the ISARIC4C (International Severe Acute Respiratory and Emerging Infection Consortium Coronavirus Clinical Characterisation Consortium) cohort, admitted with COVID-19 over the same period. The primary outcome was survival. Secondary analysis distinguished idiopathic pulmonary fibrosis from non-idiopathic pulmonary fibrosis ILD and used lung function to determine the greatest risks of death. Data from 349 patients with ILD across Europe were included, of whom 161 were admitted to the hospital with laboratory or clinical evidence of COVID-19 and eligible for propensity score matching. Overall mortality was 49% (79/161) in patients with ILD with COVID-19. After matching, patients with ILD with COVID-19 had significantly poorer survival (hazard ratio [HR], 1.60; confidence interval, 1.17-2.18;  = 0.003) than age-, sex-, and comorbidity-matched controls without ILD. Patients with an FVC of <80% had an increased risk of death versus patients with FVC ≥80% (HR, 1.72; 1.05-2.83). Furthermore, obese patients with ILD had an elevated risk of death (HR, 2.27; 1.39-3.71). Patients with ILD are at increased risk of death from COVID-19, particularly those with poor lung function and obesity. Stringent precautions should be taken to avoid COVID-19 in patients with ILD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.202007-2794OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737581PMC
December 2020