316 results found
Gulea C, Quint JK, Zakeri R, 2021, Clinical and methodological considerations when interpreting meta-analyses of beta-blocker use in patients with chronic obstructive pulmonary disease, European Heart Journal, ISSN: 0195-668X
lekarz J, Schelbert E, Naish JH, et al., 2021, Mechanisms underlying the association of chronic obstructive pulmonary disease with heart failure, JACC: Cardiovascular Imaging, ISSN: 1876-7591
groves D, karsanji U, evans R, et al., 2021, Predicting future health risk in COPD: Differential impact of disease specific and multi-morbidity based risk stratification, International Journal of COPD, ISSN: 1176-9106
Axson E, Bottle R, Cowie M, et al., 2021, The relationship between heart failure and the risk of acute exacerbation of COPD, Thorax, ISSN: 0040-6376
Rationale: Heart failure (HF) management in chronic obstructive pulmonary disease (COPD) is often delayed or suboptimal.Objectives: To examine the effect of HF and HF medication use on moderate-to-severe COPD exacerbations.Methods and Measurements: Retrospective cohort studies from 2006-2016 using nationally-representative English primary care electronic healthcare records linked to national hospital and mortality data. COPD patients with diagnosed and possible HF were identified. Possible HF defined as continuous loop diuretic use in the absence of a non-cardiac indication. Incident exposure to HF medications was defined as ≥2 prescriptions within 90 days with no gaps >90 days during ≤6 months of continuous use; prevalent exposure as 6+ months continuous use. HF medications investigated were angiotensin receptor blockers, angiotensin converting enzyme inhibitors, beta-blockers, loop diuretics, and mineralocorticoid receptor antagonists. Cox regression, stratified on sex and age; further adjusted for patient characteristics, was used to determine the association of HF on exacerbation risk.Main Results: 86,795 COPD patients were categorized as; no evidence of HF (n=60,047); possible HF (n=8,476); newly diagnosed HF (n=2,066). Newly diagnosed HF (adjusted hazard ratio (aHR): 1.45, 95% confidence interval (CI): 1.30, 1.62) and possible HF (aHR: 1.65, 95%CI: 1.58, 1.72) similarly increased exacerbation risk. Incident and prevalent use of all HF medications were associated with increased exacerbation risk. Prevalent use was associated with reduced exacerbation risk compared with incident use.Conclusions: Earlier opportunities to improve diagnosis and management of HF in the COPD population are missed. Managing HF may reduce exacerbation risk in the longer term.
Morgan A, Sinnott S-J, Smeeth L, et al., 2021, Concordance in the recording of stroke across UK primary and secondary care datasets: a population-based cohort study, British Journal of General Practice Open, Vol: 5, Pages: 1-11, ISSN: 2398-3795
Background: Previous work has demonstrated that the recording of acute health outcomes, such as myocardial infarction, may be suboptimal in primary healthcare databases. Aim: The aim of this analysis is to assess the completeness and accuracy of the recording of stroke in UK primary care. Design and setting: This is a population-based longitudinal cohort study. Methods: Cases of stroke were identified separately in Clinical Practice Research Datalink (CPRD) primary care records and linked Hospital Episode Statistics (HES). The recording of events in the same patient across the two datasets was compared. The reliability of strategies to identify fatal strokes in primary care and hospital records was also assessed. Results: Of the 75,674 stroke events that were identified in either CPRD or HES data during the period of our study, 54,929 (72.6%) were recorded in CPRD and 51,013 (67.4%) were recorded in HES. Two fifths (n=30,268) of all recorded strokes were found in both datasets (allowing for a time window of 120 days). Among these “matched” strokes the subtype was recorded accurately in approximately 75% of CPRD records (compared to coding in HES): however, 43.5% of ischaemic strokes in HES were coded as “non-specific” strokes in CPRD data. Furthermore, 48% had same day-recordings, and 56% were date-matched within ±1 day. Conclusion: The completeness and accuracy of stroke recording is improved by the use of linked hospital and primary care records. For studies that have a time-sensitive research question, we strongly recommend the use of linked, as opposed to stand-alone, CPRD data.
Quint JK, Bottle A, 2021, 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, Vol: 203, Pages: 939-940
Whittaker HR, Gulea C, Koteci A, et al., 2021, Post-acute COVID-19 sequelae in cases managed in the community or hospital in the UK: a population based study
<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>To compare post-COVID-19 sequelae between hospitalised and non-hospitalised individuals</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>Population-based cohort study</jats:p></jats:sec><jats:sec><jats:title>Setting</jats:title><jats:p>1,383 general practices in England contributing to Clinical Practice Research Database Aurum</jats:p></jats:sec><jats:sec><jats:title>Participants</jats:title><jats:p>46,687 COVID-19 cases diagnosed between 1<jats:sup>st</jats:sup> August to 17<jats:sup>th</jats:sup> October 2020 (45.4% male; mean age 40), either hospitalised within two weeks of diagnosis or non-hospitalised, and followed-up for a maximum of three months.</jats:p></jats:sec><jats:sec><jats:title>Main outcome measures</jats:title><jats:p>Event rates of new symptoms, diseases, prescriptions and healthcare utilisation in hospitalised and non-hospitalised individuals, with between-group comparison using Cox regression. Outcomes compared at 6 and 12 months prior to index date, equating to first UK wave and pre-pandemic. Non-hospitalised group outcomes stratified by age and sex.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>45,272 of 46,687 people were non-hospitalised; 1,415 hospitalised. Hospitalised patients had higher rates of 13/26 symptoms and 11/19 diseases post-COVID-19 than the community group, received more prescriptions and utilised more healthcare. The largest differences were noted for rates per 100,000 person-weeks [95%CI] of <jats:italic>breathlessness:</jats:italic> 536 [432 to 663] v. 85 [77 to 93]; <jats:italic>joint pain:</jats:italic> 295 [221 to 392] v. 168 [158 to 179]
Kadirvelu B, Burcea G, Quint JK, et al., 2021, Covid-19 does not look like what you are looking for: Clustering symptoms by nation and multi-morbidities reveal substantial differences to the classical symptom triad
<jats:title>ABSTRACT</jats:title><jats:p>COVID-19 is by convention characterised by a triad of symptoms: cough, fever and loss of taste/smell. The aim of this study was to examine clustering of COVID-19 symptoms based on underlying chronic disease and geographical location. Using a large global symptom survey of 78,299 responders in 190 different countries, we examined symptom profiles in relation to geolocation (grouped by country) and underlying chronic disease (single, co- or multi-morbidities) associated with a positive COVID-19 test result using statistical and machine learning methods to group populations by underlying disease, countries, and symptoms. Taking the responses of 7980 responders with a COVID-19 positive test in the top 5 contributing countries, we find that the most frequently reported symptoms differ across the globe: For example, fatigue 4108(51.5%), headache 3640(45.6%) and loss of smell and taste 3563(44.6%) are the most reported symptoms globally. However, symptom patterns differ by continent; India reported a significantly lower proportion of headache (22.8% vs 45.6%, p<0.05) and itchy eyes (7.0% vs. 15.3%, p<0.05) than other countries, as does Pakistan (33.6% vs 45.6%, p<0.05 and 8.6% vs 15.3%, p<0.05). Mexico and Brazil report significantly less of these symptoms. As with geographic location, we find people differed in their reported symptoms, if they suffered from specific underlying diseases. For example, COVID-19 positive responders with asthma or other lung disease were more likely to report shortness of breath as a symptom, compared with COVID-19 positive responders who had no underlying disease (25.3% vs. 13.7%, p<0.05, and 24.2 vs.13.7%, p<0.05). Responders with no underlying chronic diseases were more likely to report loss of smell and tastes as a symptom (46%), compared with the responders with type 1 diabetes (21.3%), Type 2 diabetes (33.5%) lung disease (29.3%), or hype
Mansfield KE, Mathur R, Tazare J, et al., 2021, Indirect acute effects of the COVID-19 pandemic on physical and mental health in the UK: a population-based study, The Lancet Digital Health, Vol: 3, Pages: e217-e230, ISSN: 2589-7500
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
Shah S, Quint J, Nwaru B, et al., 2021, Impact of Covid-19 National Lockdown on Asthma Exacerbations: Interrupted Time Series Analysis of English Primary Care Data, Thorax, ISSN: 0040-6376
Background: The impact of Covid-19 and ensuing national lockdown on asthma exacerbations is unclear.Methods: We conducted an interrupted time-series (lockdown on 23rd March 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 (OPCRD). We derived asthma exacerbation rates for every week and compared exacerbation rates in the period: January-August 2020 with a pre-Covid-19 period; January-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 9,949,487 patients, there were 100,165 asthma patients who experienced at least one exacerbation during 2016-2020. Of 278,996 exacerbation episodes, 49,938 (17.1%) 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-value<0.001; almost 20 episodes for every 100 asthma patients 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), 0.068-0.371 (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.
wing K, williamson E, carpenter J, et al., 2021, Real world effects of COPD medications: a cohort study with validation against results from randomised controlled trials, European Respiratory Journal, Vol: 57, Pages: 1-13, ISSN: 0903-1936
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: control group 1- people with COPD not prescribed fluticasone propionate-salmeterol (FP-SAL), control group 2- people with COPD prescribed salmeterol (SAL). 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 versus SAL (0.85, 95% CI 0.74–0.97 versus 0.88, 0.81–0.95) but not for FP-SAL versus no FP-SAL (1.30, 1.19–1.42 versus 0.75, 0.69–0.81). Active comparator results were also consistent with TORCH for mortality (hazard ratio 0.93, 0.65–1.32 versus 0.93, 0.77–1.13) and pneumonia (risk ratio 1.39, 1.04–1.87 versus 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 RCTs provides a practical way for contributing to the evidence base and supporting COPD treatment decisions.
Cook S, Eggen AE, Hopstock L, et al., 2021, Chronic Obstructive Pulmonary Disease (COPD) in population studies in Russia and Norway: Comparison of prevalence, awareness and management, International Journal of COPD, ISSN: 1176-9106
Quint J, Montonen J, Esposito D, et al., 2021, Effectiveness and Safety of COPD Maintenance Therapy with a LAMA/LABA versus LABA/ICS in a US Claims Database, Advances in Therapy, ISSN: 0741-238X
Walker JL, Grint DJ, Strongman H, et al., 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, Vol: 21, Pages: 1-14, ISSN: 1471-2458
BackgroundCharacterising 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.MethodsWe 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.ResultsOn 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.ConclusionsThe 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 countrie
Requena G, Dedman D, Quint JK, et al., 2021, The utilization and safety of umeclidinium and umeclidinium/vilanterol in UK primary care: a retrospective cohort study, The International Journal of Chronic Obstructive Pulmonary Disease, Vol: 16, Pages: 629-642, ISSN: 1176-9106
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 β2-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
Whittaker H, Bloom C, Morgan A, et al., 2021, Accelerated FEV1 decline and risk of cardiovascular disease and mortality in a primary care population of COPD patients, European Respiratory Journal, Vol: 57, ISSN: 0903-1936
Accelerated lung function decline has been associated with increased risk of cardiovascular disease (CVD) in a general population, but little is known about this association in chronic obstructive pulmonary disease (COPD). We investigated the association between accelerated lung function decline and CVD outcomes and mortality in a primary care COPD population.COPD patients without a history of CVD were identified in the Clinical Practice Research Datalink (CPRD-GOLD) primary care dataset (n=36 282). Accelerated FEV1 decline was defined using the fastest quartile of the COPD population's decline. Cox regression assessed the association between baseline accelerated FEV1 decline and a composite CVD outcome over follow-up (myocardial infarction, ischaemic stroke, heart failure, atrial fibrillation, coronary artery disease, and CVD mortality). The model was adjusted for age, gender, smoking status, BMI, history of asthma, hypertension, diabetes, statin use, mMRC dyspnoea, exacerbation frequency, and baseline FEV1 percent predicted.6110 (16.8%) COPD patients had a CVD event during follow-up; median length of follow-up was 3.6 years [IQR 1.7–6.1]). Median rate of FEV1 decline was –19.4 mL·year−1 (IQR, –40.5 to 1.9); 9095 (25%) patients had accelerated FEV1 decline (>–40.5 mL·year−1), 27 287 (75%) did not (≤ –40.5 mL·year−1). Risk of CVD and mortality was similar between patients with and without accelerated FEV1 decline (HRadj 0.98 [95%CI, 0.90–1.06]). Corresponding risk estimates were 0.99 (95%CI 0.83–1.20) for heart failure, 0.89 (95%CI 0.70–1.12) for myocardial infarction, 1.01 (95%CI 0.82–1.23) for stroke, 0.97 (95%CI 0.81–1.15) for atrial fibrillation, 1.02 (95%CI 0.87–1.19) for coronary artery disease, and 0.94 (95%CI 0.71–1.25) for CVD mortality. Rather, risk of CVD was associated with mMRC score ≥2 and ≥2 exacerbations in the year prior.CVD out
Galani J, Mulder H, Rockhold F, et al., 2021, Association of Chronic Obstructive Pulmonary Disease with Morbidity and Mortality in Patients with Peripheral Artery Disease: Insights from the EUCLID Trial, International Journal of COPD, ISSN: 1176-9106
Gulea C, Zakeri R, Alderman V, et al., 2021, Beta-blocker therapy in patients with COPD: a systematic literature review and meta-analysis with multiple treatment comparison, Respiratory Research, Vol: 22, Pages: 1-14, ISSN: 1465-9921
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.
Bachtiger P, Adamson A, Chow J-J, et al., 2021, The impact of the Covid-19 pandemic on uptake of influenza vaccine: a UK-wide observational study., JMIR Public Health and Surveillance, Vol: 7, Pages: 1-14, ISSN: 2369-2960
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.
Ngaosuwan K, Johnston DG, Godsland IF, et al., 2021, Increased mortality risk in patients with primary and secondary adrenal insufficiency, Journal of Clinical Endocrinology and Metabolism, ISSN: 0021-972X
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.
Ramakrishnan S, Janssens W, Burgel PR, et al., 2021, Standardisation of clinical assessment, management and follow-up of acute hospitalised exacerbation of COPD: a Europe-wide consensus, International Journal of COPD, Vol: 16, Pages: 321-332, ISSN: 1176-9106
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.
Ngaosuwan K, Johnston DG, Godsland IF, et al., 2021, Cardiovascular disease in patients with primary and secondary adrenal insufficiency and the role of comorbidities., J Clin Endocrinol Metab
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.
Evangelopoulos D, Chatzidiakou L, Walton H, et al., 2021, Personal exposure to air pollution and respiratory health of COPD patients in London, European Respiratory Journal, ISSN: 0903-1936
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, PM10, PM2.5, NO2, NO, CO and O3 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 NO2, NO and CO respectively. Similar results were obtained for cough and sputum. O3 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.
Bachtiger P, Adamson A, Maclean WA, et al., 2021, Increasing but inadequate intention to receive Covid-19 vaccination over the first 50 days of impact of the more infectious variant and roll-out of vaccination in UK: indicators for public health messaging
<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Objectives</jats:title><jats:p>To inform critical public health messaging by determining how changes in Covid-19 vaccine hesitancy, attitudes to the priorities for administration, the emergence of new variants and availability of vaccines may affect the trajectory and achievement of herd immunity.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>>9,000 respondents in an ongoing cross-sectional participatory longitudinal epidemiology study (LoC-19, n=18,581) completed a questionnaire within their personal electronic health record in the week reporting first effective Covid-19 vaccines, and then again after widespread publicity of the increased transmissibility of a new variant (November 13th and December 31st 2020 respectively). Questions covered willingness to receive Covid-19 vaccination and attitudes to prioritisation. Descriptive statistics, unadjusted and adjusted odds ratios (ORs) and natural language processing of free-text responses are reported, and how changes over the first 50 days of both vaccination roll-out and new-variant impact modelling of anticipated transmission rates and the likelihood and time to herd immunity.</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>Compared with the week reporting the first efficacious vaccine there was a 15% increase in acceptance of Covid-19 vaccination, attributable in one third to the impact of the new variant, with 75% of respondents “shielding” – staying at home and not leaving unless essential – regardless of health status or tier rules. 12.5% of respondents plan to change their behaviour two weeks after completing vaccination compared with 45% intending to do so only when cases have reduced to a low level. Despite the increase from 71% to 86% over this critical 50-day period, mode
Fuertes E, Marcon A, Potts L, et al., 2021, Health Impact assessment to predict the impact of tobacco price increases on COPD burden in Italy, England and Sweden, Scientific Reports, Vol: 11, ISSN: 2045-2322
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.
Magnussen H, Lucas S, Lapperre T, et al., 2021, Withdrawal of inhaled corticosteroids versus continuation of triple therapy in patients with COPD in real life: observational comparative effectiveness study, Respiratory Research, Vol: 22, ISSN: 1465-9921
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).
Gulea C, Zakeri R, Quint JK, 2021, Model-based comorbidity clusters in patients with heart failure: association with clinical outcomes and healthcare utilization, BMC Medicine, Vol: 19, Pages: 1-13, ISSN: 1741-7015
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 United States (OptumLabs Data Warehouse®) between 2008-2018. 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.
Requena G, Wolf A, Williams R, et al., 2021, Feasibility of using Clinical Practice Research Datalink data to identify patients with chronic obstructive pulmonary disease to enrol into real-world trials, Pharmacoepidemiology and Drug Safety, Vol: 30, Pages: 472-481, ISSN: 1053-8569
PurposeTo 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.MethodsA 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.ResultsA 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).ConclusionsPatients 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.
Hopkinson N, Rossi N, El-Sayed Moustafa JS, et al., 2021, Current smoking and COVID-19 risk: results from a population symptom app in over 2.4 million people, Thorax, ISSN: 0040-6376
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 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 24th March 2020 to 23rd 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.
Stone PW, Hickman KC, Steiner MC, et al., 2021, Predictors of pulmonary rehabilitation completion in the UK, ERJ Open Research, Vol: 7, Pages: 1-10, ISSN: 2312-0541
Aim Determine characteristics of people with COPD associated with completion of pulmonary rehabilitation (PR).Methods Cross-sectional analysis of 7060 people with COPD enrolled in PR between 03/01/2017 and 31/03/2017. Data were from a UK national audit of COPD care. Factors associated with PR completion were determined using mixed-effects logistic regression with a random intercept for PR service. Factors chosen for assessment based on clinical judgement and data availability were: age, gender, country, SES, Body Mass Index (BMI), referral location, programme type, start within 90 days, smoking status, oxygen therapy, GOLD stage, MRC grade, any exercise test, and any health status questionnaire.Results 4635 (66%) people with COPD completed a PR programme. People that were 60 years or older, 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 PR. 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 PR.Conclusion People with COPD were more likely to complete PR 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 PR. 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 PR completion.
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